Name: 1194-98-5|2,5-Dihydroxybenzaldehyde|98%
Brand: Ambeed
SKU: A100800
Price: 5.0 USD
Availability: InStock
Rating: 98 (25 reviews)

1
[ 1194-98-5 ]
[ 108-24-7 ]
[ 3524-69-4 ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate In diethyl ether at 20℃; for 2h;
94%	With potassium carbonate In diethyl ether at 20℃; for 3h;	2-Formyl-1,4-phenylene diacetate (S-1). Acetic anhydride (33.5 ml) was added dropwise to an Et2O solution of 2,5-dihydroxybenzaldehyde (3) (10.0 g, 72.5 mmol) and K2CO3 (20 g, 145.0mmol). The mixture was stirred at room temperature (3 h) and was filtered. The filtrate was washed with a saturated aqueous solution of Na2CO3 and H2O. The organic layer was dried, concentrated under vacuum. The white solid was triturated in pentane and filtered to obtain 15.1 g of the desired compound S-1 as a solid: 1HNMR (400 MHz, CDCl3) d 2.33 (s, CH3CO), 2.40 (s, CH3CO), 7.32 (d, J = 8.6 Hz, H3), 7.38 (dd, J = 2.8,8.8 Hz, H4), 7.63 (d, J = 2.8Hz, 1 ArH), 10.09 (s, CHO); 13C NMR (CDCl3) d 20.8, 21.0 (2CH3C(O)), 123.3, 124.6, 128.4 (3 CH), 128.7, 148.5, 149.0, (3 ArC), 169.0, 169.1 (2 C(O)), 187.6 (CHO); LC-MS (M+H+)(ESI+) and GC-MS(EI+) No ionization.
	With pyridine at -10℃;

	With diethyl ether; potassium carbonate
	With dmap In tetrahydrofuran at 20℃;
		2 To a solution of 444 mg (2.0 mmol) of 2,5-diacetoxybenzaldehyde in 30 mL toluene, obtained by treatment of 2,5-dihydroxybenzaldehyde with Ac2O -Py, 608 mg (2.0 mmol) of (triphenylphosphoranilydene)acetaldehyde was added. The mixture was stirred for 5 h at 100° C. Toluene was evaporated; the residue was re-dissolved in ethyl acetate and passed through silica gel, eluent ethyl acetate-hexane, 1:1. The solvents were evaporated and the residue was recrystallized twice from ethyl acetate-heptane, 1:2. The results were as follows: a. Yield 220 mg (44%). b. UV, λmax 221, 280 nm. c. 1H-NMR (δ, ppm): 2.27; 2.37 (2×s, 2×3H, 2×OAc), 6.77 (dd, 1H, J 7.6 and 16.1 Hz, Hα olefinic), 7.28 (d, 2H, J 1.6 Hz, H3+4), 7.65 (dd, 1H, J 0.4 and 1.6 Hz, H6), 7.76 (d, 1H, J 16.1 Hz, Hβ olefinic), 9.72 (d, 1H, J 7.6 Hz, CHO). d. MS (m/z, rel. intensity, %): 189.0 ([M-OAc]+, 66), 207.0 ([M+NH4-OAc]+, 7.4), 249.0 ([M+H]+, 63), 266.0 ([M+NH4]+, 100).

Reference： [1]Klein, Emmanuel; DeBonis, Salvatore; Thiede, Bernd; Skoufias, Dimitrios A.; Kozielski, Frank; Lebeau, Luc [Bioorganic and Medicinal Chemistry, 2007, vol. 15, # 19, p. 6474 - 6488]
[2]Salomé, Christophe; Ribeiro, Nigel; Chavagnan, Thierry; Thuaud, Frédéric; Serova, Maria; De Gramont, Armand; Faivre, Sandrine; Raymond, Eric; Désaubry, Laurent [European Journal of Medicinal Chemistry, 2014, vol. 81, p. 181 - 191]
[3]Neuberger [Biochemical Journal, 1948, vol. 43, p. 599,602]
[4]Lambooy [Journal of the American Chemical Society, 1949, vol. 71, p. 3758]
[5]Takeuchi, Yasuo; Ueda, Norihiro; Uesugi, Koji; Abe, Hitoshi; Nishioka, Hiromi; Harayama, Takashi [Heterocycles, 2003, vol. 59, # 1, p. 217 - 224]
[6]Current Patent Assignee: HOSPITAL FOR SICK CHILDREN (THE) - US2006/58297, 2006, A1 Location in patent: Page/Page column 8

2
[ 1194-98-5 ]
[ 74-88-4 ]
[ 93-02-7 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate In acetone at 20℃; for 18h;
73%	With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 1h;	Synthesis of methoxybenzaldehyde (22)-(26) General procedure: Hydroxybenzaldehyde and K2CO3 were added to iodomethane in DMF. The reaction mixture was then stirred at 80 °C for 1h. The reaction mixtures was added to H2O and AcOEt and separated. Organic layer was washed with water, dried over MgSO4 and evaporated in vacuo. Residue was purified with column chromatography (hexane/AcOEt) to give methoxybenzaldehyde.
	With potassium hydroxide

	With potassium carbonate In acetone at 25℃; for 20h;
2.4 g	With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 16h;	1 Step 1. Synthesis of 2,5-dimethoxybenzaldehyde To a solution of 2,5-dihydroxybenzaldehyde (2.76 g) and potassium carbonate (11.06 g) in dry DMF (40 mL) was added iodomethane (4.98 mL). After being stirred at 25 °C for 16 hrs, the reaction mixture was filtered through celite. The filtered cake was washed with DCM (100 mL), the combined filtrate was concentrated in vacuo. The residue was diluted with EtOAc (200 mL), washed with brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by flash silica gel chromatography (eluting withEtOAc/PE = 1/10) to give 2,5-dimethoxybenzaldehyde (2.4 g. compound AE-1) as a white solid. MS obsd. (ESL): 167.1 [(M+H)+], 189.1 [(M+Na)+]

Reference： [1]Kumar, P. Ravi; Yennam, Satyanarayana; Raghavulu; Velatooru, Loka Reddy; Kotla, Siva Reddy; Penugurti, Vasudevarao; Hota, Prasanta K.; Behera, Manoranjan; Jaya Shree [Drug Research, 2019, vol. 69, # 7, p. 406 - 414]
[2]Sato, Taki; Hotsumi, Mayumi; Makabe, Koki; Konno, Hiroyuki [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 22, p. 3520 - 3525]
[3]Waljaschko [Zhurnal Russkago Fiziko-Khimicheskago Obshchestva, 1926, vol. 58, p. 795][Chemisches Zentralblatt, 1927, vol. 98, # I, p. 1125]
[4]Location in patent: scheme or table Ravi Kumar; Behera, Manoranjan; Raghavulu; Jaya Shree; Yennam, Satyanarayana [Tetrahedron Letters, 2012, vol. 53, # 32, p. 4108 - 4113]
[5]Current Patent Assignee: ROCHE HOLDING AG - WO2020/148354, 2020, A1 Location in patent: Page/Page column 26

3
[ 1123-51-9 ]
[ 1194-98-5 ]
[ 67105-16-2 ]

Reference： [1]Chemical and pharmaceutical bulletin,1978,vol. 26,p. 191 - 198

4
[ 93-02-7 ]
[ 1194-98-5 ]

Yield	Reaction Conditions	Operation in experiment
97%	With boron tribromide In dichloromethane at -78 - 0℃; for 1h;
	With boron triiodide
	With boron tribromide In chloroform

12 g	With hydrogen bromide; acetic acid for 12h; Inert atmosphere; Reflux;	1 In a nitrogen atmosphere, 25.0 g of the compound represented by the formula (I-1-4), 100 mL of acetic acid and 100 mL of 48% hydrobromic acid were put into a reactor, and heated under reflux for 12 hours. After cooled, this was poured into 1 L of water. This was extracted with ethyl acetate and washed with salt water. The solvent was distilled away, and the remaining acetic acid was removed through azeotropic removal with toluene. Purification through column chromatography (alumina, ethyl acetate) gave 12.0 g of the compound represented by the formula (I-1-5).
14.6 g	With hydrogen bromide; acetic acid for 6h; Inert atmosphere; Reflux;	13 Under a nitrogen atmosphere, 20.0 g of a compound represented by Formula (I-11-6), 60 mL of 48% hydrobromic acid, and 60 mL of acetic acid were added to a reaction container, and the mixture was heated under reflux for 6 hours. After cooling, a liquid separation treatment was carried out with 200 mL of ethyl acetate. Purification was performed by column chromatography (alumina) to obtain 14.6 g of a compound represented by Formula (I-11-7).
18.7 g	With boron tribromide In dichloromethane for 2h; Inert atmosphere; Cooling with ice;	5 A reaction vessel was charged with 25.0 g of2,5-dimethoxybenzaldehyde and 200 mE of dichloromethHane in a nitrogen atmosphere. While the reaction vessel was cooled with ice, 113.1 g of boron tribromide was added dropwise, and the mixture was stirred for 2 hours. After the mixture was poured into iced water, the resulting mixture was extracted with ethyl acetate and washed with water and then brine. The product was purified by column chromatography (alumina, ethyl acetate) to thereby obtain 18.7 g of a compound represented by formula (1-5-6).
18.7 g	With boron tribromide In dichloromethane for 2h; Inert atmosphere; Cooling with ice;	5 Under a nitrogen atmosphere, 25.0 g of 2,5-dimethoxybenzaldehyde and 200 mL of dichloromethane were added to the reaction vessel.While ice-cooling, 113.1 g of boron tribromide was added dropwise and stirred for 2 hours.After pouring into ice water, extraction was carried out with ethyl acetate, followed by washing with water and brine.Purification by column chromatography (alumina, ethyl acetate) gave 18.7 g of the compound of formula (I-5-6).
14.6 g	With hydrogen bromide; acetic acid for 6h; Inert atmosphere; Reflux;	14 20.0 g of the compound represented by the formula (I-9-6) under a nitrogen atmosphere60% of 48% hydrobromic acid and 60 mL of acetic acid were placed in a reaction vessel, and the mixture was heated under reflux for 6 hours.After cooling, the mixture was treated with 200 mL of ethyl acetate.Purification by column chromatography (alumina, ethyl acetate) gave 14.6 g of the compound of formula (I-9-7).
23.5 g	Stage #1: 2,5-dimethoxybenzaldehyde With aluminum (III) chloride In 1,2-dichloro-ethane at 65℃; for 3h; Inert atmosphere; Stage #2: With hydrogenchloride In 1,2-dichloro-ethane at 65℃; for 2h;	1.3; 2.3 3) Synthesis of 2,5-dihydroxybenzaldehyde Add 43.5 g (261.7 mmol) of 2,5-dimethoxybenzaldehyde, 250 mL of dichloroethane to a 500 mL four-necked flask, protected by nitrogen,76.4 g (523.4 mmol) of anhydrous aluminum trichloride was added in portions under mechanical stirring,After the addition, react at 65 ° C for 3 hours, cool down to 10 ° C, and slowly add 150 mL of water.Distilled dichloroethane was recovered under reduced pressure, and 150 mL of ethyl acetate was added at 40 ° C to dissolve.Add 50mL of water and separate the layers.The organic layer was added to 200 g of a 30% sodium bisulfite solution with stirring, and the layers were separated.75g of concentrated hydrochloric acid was added to the water layer, and the temperature was raised at 65 ° C under nitrogen for 2 hours to react.Reduce the temperature to 35 ° C, add 5g of activated carbon to decolorize, and extract the filtrate with ethyl acetate.The organic layer was washed with saturated brine, and the solvent was recovered by rotary evaporation. 30 mL of dichloroethane was added for crystallization.23.5 g of a yellow solid was obtained.
14.6 g	With hydrogen bromide; acetic acid for 6h; Inert atmosphere; Reflux;	14 In a nitrogen atmosphere, 20.0 g of a compound represented by formula (I-9-6), 60 mL of a 48% hydrobromic acid, and 60 mL of acetic acid were added, and the resulting mixture was refluxed under heating for 6 hours. After cooling, a liquid separation process was performed by using 200 mL of ethyl acetate. Purification was performed by column chromatography (alumina, ethyl acetate) so as to obtain 14.6 g of a compound represented by formula (I-9-7).

Reference： [1]Li, Chaomin; Johnson, Richard P.; Porco Jr., John A. [Journal of the American Chemical Society, 2003, vol. 125, # 17, p. 5095 - 5106]
[2]Lansinger,J.M.; Ronald,R.C. [Synthetic Communications, 1979, vol. 9, p. 341 - 349]
[3]Illescas, Beatriz M.; Martin, Nazario [Journal of Organic Chemistry, 2000, vol. 65, # 19, p. 5986 - 5995]
[4]Current Patent Assignee: DIC CORP. - US2018/312481, 2018, A1 Location in patent: Paragraph 0091; 0094; 0110
[5]Current Patent Assignee: DIC CORP. - US2018/354922, 2018, A1 Location in patent: Paragraph 0142; 0147
[6]Current Patent Assignee: DIC CORP. - US2019/62256, 2019, A1 Location in patent: Paragraph 0131
[7]Current Patent Assignee: DIC CORP. - TW2019/12621, 2019, A Location in patent: Paragraph 0192; 0197
[8]Current Patent Assignee: DIC CORP. - TW2019/14995, 2019, A Location in patent: Paragraph 0150; 0151; 0157
[9]Current Patent Assignee: JIANGXI RV PHARMACEUTICAL - CN110330417, 2019, A Location in patent: Paragraph 0013; 0018-0020; 0025-0026
[10]Current Patent Assignee: DIC CORP. - US2020/165215, 2020, A1 Location in patent: Paragraph 0130; 0135

5
[ 1194-98-5 ]
[ 22802-67-1 ]
[ 151391-84-3 ]

Reference： [1]Journal of Medicinal Chemistry,1993,vol. 36,p. 4094 - 4098

6
[ 1194-98-5 ]
[ 107-30-2 ]
[ 13709-07-4 ]

Yield	Reaction Conditions	Operation in experiment
98%	With potassium carbonate In acetone at 0 - 20℃; for 10h;
81%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 25℃; for 15.1667h; Inert atmosphere;	84.1 Step 1: Synthesis of Intermediate K2 A three-necked reactor equipped with a thermometer was charged with 10.0 g (72.4 mmol) of 2,5-dihydroxybenzaldehyde and 200 ml of dichloromethane under a nitrogen stream to prepare a solution. The solution was cooled to 0° C. After the addition of 35.06 g (0.27 mol) of diisopropylethylamine to the solution, 23.32 g (0.29 mmol) of chloromethyl methyl ether was added to the mixture over 10 minutes. After the dropwise addition, the reaction mixture was heated to 25° C., and stirred for 15 hours. After completion of the reaction, 1000 ml of distilled water was added to the reaction mixture, followed by extraction twice with 200 ml of dichloromethane. The organic layer was dried over anhydrous sodium sulfate, and sodium sulfate was separated by filtration. The filtrate was concentrated using a rotary evaporator, and the concentrate was purified by silica gel column chromatography (THF:toluene=1:19) to obtain 13.26 g of an intermediate K2 as a colorless oil (yield: 81%). [0700] The structure of the target product was identified by 1H-NMR. [0701] 1H-NMR (500 MHz, CDCl3, TMS, δ ppm): 10.46 (s, 1H), 7.49 (d, 1H, J=3.0 Hz), 7.23 (dd, 1H, J=3.0 Hz, 9.0 Hz), 7.17 (d, 1H, J=9.0 Hz), 5.25 (s, 2H), 5.15 (s, 2H), 3.52 (s, 3H), 3.47 (s, 3H)
57%	With triethylamine In diethyl ether; acetic acid methyl ester for 25h; Ambient temperature;

55%	With N-ethyl-N,N-diisopropylamine In dichloromethane at 0 - 20℃; for 8h;	3,4-Dimethoxymethoxybenzaldehyde (10) General procedure: Chloromethylmethyl ether (2.24 mL, 29.5mmol) was added to a solution of 3,4-dihydroxybenzaldehyde (2.00 g, 14.5 mmol) inCH2Cl2 (40 mL) at 0°C. DIPEA (10.0 mL, 57.4 mmol) was added to the mixture, whichwas allowed to stir at room temperature. After 8 h, the mixture was added to saturatedNH4Cl (10 mL) and extracted with AcOEt. Then obtained organic layer was washed with1M NaOH, dried over MgSO4, and concentrated in vacuo to give 10 (3.00 g, 94%) as acolorless oil.
	With potassium carbonate In acetone for 0.5h;
	With potassium carbonate In acetone at 0 - 20℃; for 0.75h;	2.7. Synthesis of MOMO protection benzaldehyde 2 General procedure: K2CO3 (10 equiv) was added with stirring at 0-5 °C (ice-waterbath) to a solution of hydroxylbenzaldehyde (1 equiv) in dry acetone,When the solution was cooled to 0-5 °C chloromethyl methylether (1.5 equiv; dependent on the number of the hydroxyl groups)was slowly added over a period of 15 min to keep the temperatureunder 5 °C. The reaction mixture was stirred at room temperaturefor another 30 min, quenched by the addition of cold distilledwater and extracted with EtOAc. The combined organic layer waswashed with distilled water and brine and then dried over Na2SO4.The filtered organic layer was concentrated under a vacuum andthe residue was purified by silica gel column chromatography elutingwith n-hexane and EtOAc to give compound 2: a colorless orlight yellow oil (80-95% yield).
	With potassium carbonate In acetone at 0℃; for 4.5h; Inert atmosphere;	16 2.1.2.1. Methoxymethoxy (MOMO) protection. General procedure: In a 100 mLoven-dried round bottom flask under argon protection, hydroxylaldehydeor acetophenone (10 mmol, 1 equiv) and 60 mL extradry acetone were combined. After complete dissolution, thesolution was cooled in an ice bath for 10 min and then K2CO3(100 mmol, 10 equiv) was added. While stirring, methoxymethylchloride (50 mmol, 5 equiv) was added dropwise. The mixture wasfirst stirred at 0 C for 30 min and then at under reflux conditionsfor 4 h. The mixture was cooled to room temperature and salts wereremoved by suction filtration. The solvent was removed by rotaryevaporation to obtain the crude product which was further purifiedby automated medium performance liquid chromatography elutingwith an ethyl acetate/hexanes gradient (0-20%).

Reference： [1]Yajima, Arata; Urao, Shota; Katsuta, Ryo; Nukada, Tomoo [European Journal of Organic Chemistry, 2014, vol. 2014, # 4, p. 731 - 738] Yajima, Arata; Urao, Shota; Katsuta, Ryo; Nukada, Tomoo [European Journal of Organic Chemistry, 2014, vol. 2014, # 4, p. 731 - 738]
[2]Current Patent Assignee: ZEON CORPORATION - US2015/175564, 2015, A1 Location in patent: Paragraph 0698; 0699; 0700
[3]Ahmad; Bruce [Synthetic Communications, 1994, vol. 24, # 12, p. 1639 - 1649]
[4]Hotsumi, Mayumi; Tajiri, Misato; Nikaido, Yuri; Sato, Taki; Makabe, Koki; Konno, Hiroyuki [Bioorganic and Medicinal Chemistry Letters, 2019, vol. 29, # 16, p. 2157 - 2161]
[5]Lim, Soon Sung; Jung, Sang Hoon; Ji, Jun; Shin, Kuk Hyun; Keum, Sam Rok [Journal of Pharmacy and Pharmacology, 2001, vol. 53, # 5, p. 653 - 668]
[6]Jiang, Wen-Jun; Ishiuchi, Kan'Ichiro; Furukawa, Megumi; Takamiya, Tomoko; Kitanaka, Susumu; Iijima, Hiroshi [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 21, p. 6922 - 6929]
[7]Hofmann, Emily; Webster, Jonathan; Do, Thuy; Kline, Reid; Snider, Lindsey; Hauser, Quintin; Higginbottom, Grace; Campbell, Austin; Ma, Lili; Paula, Stefan [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 4, p. 578 - 587]

7
[ 626-35-7 ]
[ 1194-98-5 ]
[ 158521-86-9 ]

Yield	Reaction Conditions	Operation in experiment
75%	With <i>L</i>-proline In ethanol at 20℃; for 4h;	General procedure for the synthesis of 3-nitrocoumarins3 and 5 General procedure: To the solution of salicylaldehyde (1 mmol) and ethylnitroacetate (1 mmol) in 3 cm3 ethanol, L-proline(30 mol %) was added. The reaction mixture was stirredfor an appropriate time. After completion of the reaction(as monitored by TLC), the solvent was evaporated and theproduct so obtained was dissolved in 12 cm3 CHCl3 andwashed with water (3 9 10 cm3). The organic layer waswashed with 10 cm3 brine, dried over anhydrous NaSO4,and evaporated under reduced pressure. The residue wasrecrystallized from ethanol (3, 5a, 5b, and 5h) or purifiedby silica gel column using chloroform/methanol (9:1) aseluent (5c-5g). The combined aqueous layers, containingL-proline, were evaporated, washed with ether, dried at45 C, and reused for next run.
	With 4-methyl-morpholine; titanium tetrachloride Yield given. Multistep reaction;

Reference： [1]Sharma, Rajesh Kumar; Priyanka; Katiyar, Diksha [Monatshefte fur Chemie, 2016, vol. 147, # 12, p. 2157 - 2161]
[2]Perrella; Chen; Behrens; Kaltenbach III; Seitz [Journal of Medicinal Chemistry, 1994, vol. 37, # 14, p. 2232 - 2237]

8
[ 1194-98-5 ]
[ 1099-45-2 ]
[ 6093-68-1 ]

Yield	Reaction Conditions	Operation in experiment
85%	With N,N-diethylaniline for 6h; Heating;
70%	With N,N-diethylaniline for 2h; Heating;
	In various solvent(s) for 0.666667h;

Reference： [1]Cerqueira, Nuno M. F. S. A.; Oliveira-Campos, Ana M. F.; Coelho, Paulo J.; Melo De Carvalho, Luis H.; Samat, Andre; Guglielmetti, Robert [Helvetica Chimica Acta, 2002, vol. 85, # 2, p. 442 - 450]
[2]Harayama, Takashi; Katsuno, Keiko; Nishioka, Hiromi; Fujii, Masako; Nishita, Yoshitaka; et al. [Heterocycles, 1994, vol. 39, # 2, p. 613 - 622]
[3]Von Weymarn; Murphy [Chemical Research in Toxicology, 2001, vol. 14, # 10, p. 1386 - 1392]

9
[ 1194-98-5 ]
[ 18162-48-6 ]
[ 860613-37-2 ]

Yield	Reaction Conditions	Operation in experiment
93%	Stage #1: 2,5-Dihydroxybenzaldehyde With 1H-imidazole In dichloromethane Stage #2: tert-butyldimethylsilyl chloride In dichloromethane at 20℃;	5.a 5-(tert-butyldimethylsilyloxy)-2-hydroxybenzaldehyde Imidazole (15.53 g, 0.228 mol) and 2,5-dihydroxybenzaldehyde (15.0 g, 0.109 mol) were dissolved in DCM (250 mL) to give a brown solution. TBSCI (18.0 g, 0.199 mol) was added in portions and the mixture was stirred at room temperature overnight. After removal of all volatiles under reduced pressure, the crude residue was dispersed between petroleum ether (100 mL) and water (100 mL). The aqueous layer was extracted with petroleum ether (3 x 100 mL), before concentration of the combined organic layers to give 27.78 g of dark green oil. This was further purified by FCC (eluent TBME/PE 2:98), to afford 25.54 g (93% yield) of 52a as a yellow oil.
93%	With 1H-imidazole In dichloromethane at 20℃;	5.a Synthesis of 2,3-dihydrobenzofuran-2-yl and benzofuran-2-yl Analogues of aryloxypropanolamines (Scheme 5) a) 5-(tert-butyldimethylsilyloxy)-2-hydroxybenzaldehyde 52a: Imidazole (15.53 g, 0.228 mol) and 2,5-dihydroxybenzaldehyde (15.0 g, 0.109 mol) were dissolved in DCM (250 mL) to give a brown solution. TBSCl (18.0 g, 0.199 mol) was added in portions and the mixture was stirred at room temperature overnight. After removal of all volatiles under reduced pressure, the crude residue was dispersed between petroleum ether (100 mL) and wafer (100 mL). The aqueous layer was extracted with petroleum ether (3*100 mL), before concentration of the combined organic layers to give 27.78 g of dark green oil. This was further purified by FCC (eluent TBME/PE 2:98), to afford 25.54 g (93% yield) of 52a as a yellow oil.
88%	With 1H-imidazole In dichloromethane Ambient temperature;

84%	With 1H-imidazole In dichloromethane at 20℃; for 18h;
82%	With 1H-imidazole In dichloromethane at 20℃;	8 Synthesis of Compound 2: Synthesis of Compound 2: To the solution of 5-hydroxy salicylaldehyde (1.7 g, 12.33 mmol) in dry DCM were added /er-butyl demethylsilyl chloride (2.78 g, 18.48 mmol) and imidazole (2.51 g, 36.91 mmol) at room temperature. Reaction continued at same temperature overnight. After completion of the reaction, water was added and the organic phase was extracted into dichloromethane. The volatiles were removed under the reduced pressure to obtain the crude product, which was purified by column chromatography to obtain 5-((tert-butyldimethylsilyl)oxy)-2- hydroxybenzaldehyde (Compound 2, 2.5 g, 82 %). XH NMR (CDC13, 500 MHz): 10.67 (s, 1H), 9.84 (s, 1H), 7.08 (dd, J = 8.8, 2.9 Hz, 1H), 7.0 (d, J = 2.6 Hz, 1H), 6.91 (d, J = 8.8 Hz, 1H), 0.98 (s, 9H), 0.20 (s, 6H). ESIMS: m/z 253 (M++l).
82%	With 1H-imidazole In dichloromethane at 20℃;	8 Synthesis of Compound 2: To the solution of 5-hydroxy salicylaldehyde (1.7 g, 12.33 mmol) in dry DCM wereadded ter-butyl demethylsilyl chloride (2.78 g, 18.48 mmol) and imidazole (2.51 g, 36.91 mmol) at room temperature.Reaction continued at same temperature overnight. After completion of the reaction, water was added and the organicphase was extracted into dichloromethane. The volatiles were removed under the reduced pressure to obtain the crudeproduct, which was purified by column chromatography to obtain 5-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde(Compound 2, 2.5 g, 82 %).[0108] 1H NMR (CDCl3, 500 MHz): 10.67 (s, 1H), 9.84 (s, 1H), 7.08 (dd, J = 8.8, 2.9 Hz, 1H), 7.0 (d, J = 2.6 Hz, 1H),6.91 (d, J = 8.8 Hz, 1H), 0.98 (s, 9H), 0.20 (s, 6H). ESIMS: m/z 253 (M++1)
81%	With 1H-imidazole In dichloromethane for 12h; Inert atmosphere; Cooling with ice;
	With 1H-imidazole In dichloromethane for 18h;
	With 1H-imidazole In dichloromethane at 0 - 20℃; for 1h;
	With 1H-imidazole In dichloromethane at 20℃; for 0.25h;	1.1A; 16A 2-(benzyloxy)-5-((ri-butyldimethylsilyl)oxy)benzaldehyde A 2 L round bottom flask was charged with 2,5-dihydroxybenzaldehyde (30 g), imidazole (29.6 g) and dichloromethane (543 mL). The flask was placed in a water bath and solid tert- butylchlorodimethylsilane (32.7 g) was added. The reaction mixture was stirred at ambient temperature for 15 minutes at which point thin-layer chromatography indicated complete consumption of starting material. The reaction mixture was poured into a separatory funnel with 200 mL water. The biphasic mixture was shaken and layers were separated. The aqueous layer was washed with 100 mL dichloromethane and the organic layers were combined. After drying over Na2S04, filtration, and concentration, the crude material was used as such for the next step. A 1 L three-necked round bottom flask equipped with an internal temperature probe, a reflux condenser, and a stir bar was charged with 5- ((ieri-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde (45 g, 178 mmol) in acetone (297 mL). Solid K2CO3 (27.1 g) was added followed by dropwise addition of neat benzyl bromide (21.21 mL). The mixture was stirred at ambient temperature for 10 minutes and was heated to 55 °C. The reaction was continued overnight. The reaction was cooled to ambient temperature and was poured over cold water (200 mL). The mixture was transferred to a 1 L separatory funnel. The crude product was extracted with ethyl acetate (3 χ 250 mL). The combined organic layers were dried over Na2SC>4, filtered, and concentrated. The crude material was purified by silica gel chromatography over a 330 g column on a Grace Reveleris system (0-5% ethyl acetate/heptanes elution gradient). Fractions containing the desired product were combined, concentrated and dried under vacuum to obtain the title compound. 'H NMR (501 MHz, DMSO-ck) δ ppm 10.35 (s, 1H), 7.51 -7.47 (m, 2H), 7.42-7.37 (m, 2H), 7.35-7.31 (m, 1 H), 7.22 (d, 1H), 7.15 (dd, 1H), 7.1 1 (d, 1H), 5.21 (s, 2H), 0.93 (s, 10H), 0.16 (s, 7H).
	With 1H-imidazole; potassium carbonate In dichloromethane at 20℃; for 0.25h;	16.16A 2-(benzyloxy)-5-((tert-butyldimethylsilyl)oxy)benzaldehyde Example 16A 2-(benzyloxy)-5-((tert-butyldimethylsilyl)oxy)benzaldehyde A 2 L round bottom flask was charged with 2,5-dihydroxybenzaldehyde (30 g), imidazole (29.6 g) and dichloromethane (543 mL). The flask was placed in a water bath and solid tert-butylchlorodimethylsilane (32.7 g) was added. The reaction mixture was stirred at ambient temperature for 15 minutes at which point thin-layer chromatography indicated complete consumption of starting material. The reaction mixture was poured into a separatory funnel with 200 mL water. The biphasic mixture was shaken and layers were separated. The aqueous layer was washed with 100 mL dichloromethane and the organic layers were combined. The organic layer was dried over sodium sulfate, filtered, and concentrated and the material was used in the next step. A 1 L three-necked round bottom flask equipped with an internal temperature probe, a reflux condenser, and a stir bar was charged with 5-((tert-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde (45 g, 178 mmol) in acetone (297 mL). Solid K2CO3 (27.1 g) was added followed by dropwise addition of neat benzyl bromide (21.21 mL). The mixture was stirred at ambient temperature for 10 minutes and heated to 55° C. The reaction mixture stirred overnight. The reaction mixture was cooled to ambient temperature then poured over cold water (200 mL). The mixture was then transferred to a 1 L separatory funnel. The crude product was extracted with ethyl acetate (3*250 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography over a 330 g column on a Grace Reveleris system (0-5% ethyl acetate/heptanes elution gradient). Fractions containing the desired product were combined, concentrated and dried under vacuum to obtain the title compound. 1H NMR (501 MHz, dimethyl sulfoxide-d6) δ ppm 10.35 (s, 1H), 7.51-7.47 (m, 2H), 7.42-7.37 (m, 2H), 7.35-7.31 (m, 1H), 7.22 (d, 1H), 7.15 (dd, 1H), 7.11 (d, 1H), 5.21 (s, 2H), 0.93 (s, 10H), 0.16 (s, 7H).
	With 1H-imidazole In dichloromethane at 20℃; for 0.25h;	1M Example 1M 2-(benzyloxy)-5-((/er/-butyldimethylsilyl)oxy)benzaldehyde A 2 L round bottom flask was charged with 2,5-dihydroxybenzaldehyde (30 g), imidazole (29.6 g) and dichloromethane (543 mL). The flask was placed in a water bath and solid tert- butylchlorodimethylsilane (32.7 g) was added. The reaction mixture was stirred at ambient temperature for 15 minutes at which point thin-layer chromatography indicated complete consumption of starting material. The reaction mixture was poured into a separatory runnel with 200 mL water. The biphasic mixture was shaken and the layers were separated. The aqueous layer was washed with 100 mL dichloromethane and the organic layers were combined. The organic layer was dried over sodium sulfate, filtered, and concentrated and the material was used in the next step. A 1 L three-necked round bottom flask equipped with an internal temperature probe, a reflux condenser, and a stir bar was charged with 5-((/eri-butyldimethylsilyl)oxy)-2-hydroxybenzaldehyde (45 g, 178 mmol) in acetone (297 mL). Solid K2CO3 (27.1 g) was added followed by dropwise addition of neat benzyl bromide (21.21 mL). The mixture was stirred at ambient temperature for 10 minutes and heated to 55 °C. The reaction mixture was stirred overnight. The reaction mixture was cooled to ambient temperature then poured over cold water (200 mL). The mixture was then transferred to a 1 L separatory funnel. The crude product was extracted with ethyl acetate (3 x 250 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated. The crude material was purified by silica gel chromatography over a 330 g column on a Grace Reveleris system (0-5% ethyl acetate/heptanes elution gradient). Fractions containing the desired product were combined, concentrated and dried under vacuum to obtain the title compound. NMR (501 MHz, dimethyl sulfoxide-cfe) δ ppm 10.35 (s, 1H), 7.51-7.47 (m, 2H), 7.42-7.37 (m, 2H), 7.35-7.31 (m, 1H), 7.22 (d, 1H), 7.15 (dd, 1H), 7.11 (d, 1H), 5.21 (s, 2H), 0.93 (s, 9H), 0.16 (s, 6H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF NOTTINGHAM - WO2013/121209, 2013, A1 Location in patent: Page/Page column 21
[2]Current Patent Assignee: UNIVERSITY OF NOTTINGHAM - US2015/51270, 2015, A1 Location in patent: Paragraph 0174; 0175; 0176
[3]Liu, Aijun; Dillon, Kathleen; Campbell, Robert M.; Cox, Don C.; Huryn, Donna M. [Tetrahedron Letters, 1996, vol. 37, # 22, p. 3785 - 3788]
[4]Location in patent: scheme or table Tasler, Stefan; Baumgartner, Roland; Ammendola, Astrid; Schachtner, Josef; Wieber, Tanja; Blisse, Marcus; Rath, Sandra; Zaja, Mirko; Klahn, Philipp; Quotschalla, Udo; Ney, Peter [Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 20, p. 6108 - 6115]
[5]Current Patent Assignee: CITY UNIVERSITY OF NEW YORK - WO2013/25790, 2013, A2 Location in patent: Page/Page column 95; 96
[6]Current Patent Assignee: CITY UNIVERSITY OF NEW YORK - EP2744487, 2016, B1 Location in patent: Paragraph 0106 - 0108
[7]Vedachalam, Seenuvasan; Zeng, Jing; Gorityala, Bala Kishan; Antonio, Meraldo; Liu, Xue-Wel [Organic Letters, 2010, vol. 12, # 2, p. 352 - 355]
[8]Kodela, Ravinder; Chattopadhyay, Mitali; Kashfi, Khosrow [MedChemComm, 2013, vol. 4, # 11, p. 1472 - 1481]
[9]Ding, Jiaming; Chen, Jiafu; Mao, Weipeng; Huang, Junrou; Ma, Da [Organic and Biomolecular Chemistry, 2017, vol. 15, # 37, p. 7894 - 7897]
[10]Current Patent Assignee: ABBVIE INC - WO2019/35927, 2019, A1 Location in patent: Paragraph 00152; 00300
[11]Current Patent Assignee: ABBVIE INC - US2019/55264, 2019, A1 Location in patent: Paragraph 0606
[12]Current Patent Assignee: ABBVIE INC - WO2019/35911, 2019, A1 Location in patent: Paragraph 00156

10
[ 1194-98-5 ]
[ 119-34-6 ]
2-[(E)-4-Hydroxy-3-nitro-phenylimino]-methyl}-benzene-1,4-diol [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,1997,vol. 7,p. 365 - 368

11
[ 1194-98-5 ]
[ 54977-92-3 ]
N-Benzyl-4-[1-(2,5-dihydroxy-phenyl)-meth-(E)-ylidene]-amino}-benzamide [ No CAS ]

Reference： [1]Journal of Medicinal Chemistry,2001,vol. 44,p. 441 - 452

12
[ 1194-98-5 ]
[ 241127-72-0 ]

Yield	Reaction Conditions	Operation in experiment
100%	With bromine In chloroform Inert atmosphere;
97%	With bromine In chloroform at 20℃; for 3h;
97%	With bromine In chloroform at 20℃; for 3h;

95%	With bromine In chloroform for 3.5h; Inert atmosphere;
94%	With bromine In chloroform at 20℃; for 1.5h;
93%	With bromine In chloroform at 20℃; for 2h; regioselective reaction;
86%	With bromine In chloroform
80%	With bromine; sodium acetate In chloroform at 20℃; for 3h;
79%	With bromine In chloroform at 20℃; for 2h; Under Ar;	6 To a stirred solution of 2,5-dihydroxybenzaldehyde (2.00 g; 14.5 mmol) in CHCl3 (90 mL) at room temperature and under an argon atmosphere was added a solution of Br2 (2.31 g. 14.5 mmol) in CHCl3 (60 mL) dropwise over one hour. Upon completion of the addition, the reaction mixture was stirred for one hour, then diluted with CH2Cl2 (350 mL). The resulting solution was washed by stirring for twenty minutes with saturated aqueous NaHCO3, dried (MgSO4), and concentrated in vacuo to give a bright yellow solid 2.5 g (79%) suitable for further transformation.
57.2%	With bromine; sodium phosphate In chloroform at 20℃; for 2.5h;	12.S12A Step S_12A: Synthesis of 2-bromo-3,6-dihydroxy-benzaldehyde (12A) Step S12A: Synthesis of 2-bromo-3,6-dihydroxy-benzaldehyde (12A) 2,5-dihydroxy-benzaldehyde (100g, 0.72mol) was dissolved in chlorform (1L). To the solution was added Na3PO4 (77g), followed by Br2 (150g, 0.94mol) dropwise at room temperature. The mixture was stirred for 2.5 hours. To the reaction mixture was added aq.NH4Cl. The precipitated solid was collected by filtration, then dissolved in ethyl acetate, washed with water. The organic layer was dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel to give product 12A (90g, 57.2% yield).
57.2%	With bromine; sodium phosphate In chloroform at 20℃; for 2.5h;	12.s.12A Step S_12A: Synthesis of 2-bromo-3,6-dihydroxy-benzaldehyde (12A) Step S12A: Synthesis of 2-bromo-3,6-dihydroxy-benzaldehyde (12A) 2,5-dihydroxy-benzaldehyde (100 g, 0.72 mol) was dissolved in chlorform (1L). To the solution was added Na3PO4 (77 g), followed by Br2 (150 g, 0.94 mol) dropwise at room temperature. The mixture was stirred for 2.5 hours. To the reaction mixture was added aq.NH4Cl. The precipitated solid was collected by filtration, then dissolved in ethyl acetate, washed with water. The organic layer was dried over anhydrous Na2SO4, concentrated and purified by column chromatography on silica gel to give product 12A (90 g, 57.2% yield).
	With bromine In chloroform at 20℃;
	With bromine In chloroform Inert atmosphere; regioselective reaction;
	In chloroform at 20℃; regioselective reaction;
	With bromine regioselective reaction;
	With bromine In chloroform regioselective reaction;
	With bromine In chloroform at 20℃;

Reference： [1]Location in patent: scheme or table Wang, Zhang; Dai, Mingji; Park, Peter K.; Danishefsky, Samuel J. [Tetrahedron, 2011, vol. 67, # 52, p. 10249 - 10260]
[2]Goddard, Mary-Lorène; Tabacchi, Raffaele [Tetrahedron Letters, 2006, vol. 47, # 6, p. 909 - 911]
[3]Carr, James L.; Offermann, Daniel A.; Holdom, Mary D.; Dusart, Philip; White, Andrew J. P.; Beavil, Andrew J.; Leatherbarrow, Robin J.; Lindell, Stephen D.; Sutton, Brian J.; Spivey, Alan C. [Chemical Communications, 2010, vol. 46, # 11, p. 1824 - 1826]
[4]Location in patent: experimental part Pospisil, Jiri; Mueller, Christoph; Fuerstner, Alois [Chemistry - A European Journal, 2009, vol. 15, # 24, p. 5956 - 5968]
[5]Hu, Yongbo; Li, Chaomin; Kulkarni, Bheemashankar A.; Strobel, Gary; Lobkovsky, Emil; Torczynski, Richard M.; Porco Jr., John A. [Organic Letters, 2001, vol. 3, # 11, p. 1649 - 1652]
[6]Narita, Koichi; Kimura, Ryuhei; Satoh, Hiroka; Watanabe, Kazuhiro; Yoshimura, Yuichi [Chemical and Pharmaceutical Bulletin, 2021, vol. 69, # 2, p. 232 - 235]
[7]Ni, Hua; Xia, Chao; Zhao, Yu [Medicinal Chemistry Research, 2017, vol. 26, # 11, p. 2861 - 2869]
[8]Hayashi, Ken-ichiro; Yamazoe, Atsushi; Ishibashi, Yuki; Kusaka, Naoyuki; Oono, Yutaka; Nozaki, Hiroshi [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 9, p. 5331 - 5344]
[9]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - EP1367046, 2003, A1 Location in patent: Page 26
[10]Current Patent Assignee: SHANGHAI TANGRUN PHARMACEUTICALS - EP2740734, 2014, A1 Location in patent: Paragraph 0092; 0093
[11]Current Patent Assignee: SHANGHAI TANGRUN PHARMACEUTICALS - US2014/163219, 2014, A1 Location in patent: Paragraph 0198-0200
[12]Li, Chaomin; Johnson, Richard P.; Porco Jr., John A. [Journal of the American Chemical Society, 2003, vol. 125, # 17, p. 5095 - 5106]
[13]Location in patent: scheme or table Gladding, Jeffery A.; Bacci, James P.; Shaw, Scott A.; Smith III, Amos B. [Tetrahedron, 2011, vol. 67, # 35, p. 6697 - 6706]
[14]Little, Andrew; Porco, John A. [Organic Letters, 2012, vol. 14, # 11, p. 2862 - 2865]
[15]Takao, Ken-Ichi; Nanamiya, Ryuki; Fukushima, Yuuki; Namba, Ayumi; Yoshida, Keisuke; Tadano, Kin-Ichi [Organic Letters, 2013, vol. 15, # 21, p. 5582 - 5585]
[16]Knueppel, Daniel; Yang, Jingyue; Cheng, Bo; Mans, Douglas; Martin, Stephen F. [Tetrahedron, 2015, vol. 71, # 35, p. 5741 - 5757]
[17]Nakayama, Atsushi; Sato, Hideo; Karanjit, Sangita; Hayashi, Naoki; Oda, Masataka; Namba, Kosuke [European Journal of Organic Chemistry, 2018, vol. 2018, # 29, p. 4013 - 4017]

13
[ 1194-98-5 ]
[ 21204-67-1 ]
[ 123064-80-2 ]
(Z)-3-(2,5-Dihydroxy-phenyl)-acrylic acid methyl ester [ No CAS ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2001,vol. 11,p. 1173 - 1176

14
[ 1194-98-5 ]
[ 100-39-0 ]
[ 6109-54-2 ]

Yield	Reaction Conditions	Operation in experiment
96%	With potassium carbonate In N,N-dimethyl-formamide
92%	Stage #1: 2,5-Dihydroxybenzaldehyde In 1,2-dimethoxyethane at 80℃; Inert atmosphere; Stage #2: benzyl bromide In 1,2-dimethoxyethane; N,N-dimethyl-formamide for 12h;
91%	With potassium carbonate In acetone Heating;

87%	With potassium carbonate In acetonitrile for 4h; Heating;
76%	With sodium hydride In N,N-dimethyl-formamide at 0 - 20℃; for 24h;	7.1.1 To an N,N-dimethylformamide (100 mL) solution of 2,5-dihydroxybenzaldehyde (10.0 g, 72.4 mmol) were added sodium hydride (5.79 g, 145 mmol) and benzyl bromide (18.9 mL, 159 mmol) at 0°C, which was stirred at room temperature for 24 hours. Water was added to the reaction solution at 0°C followed by extraction with ethyl acetate. The organic layer was washed with water and sat. NaCl, followed by drying over anhydrous magnesium sulfate and filtering. The filtrate was concentrated under a reduced pressure and the residue was purified by silica gel column chromatography (heptane:ethyl acetate = 4:1) to obtain the title compound (17.6 g, 76%) as a white solid. 1H-NMR spectrum (DMSO-d6) δ (ppm): 5.11 (2H, s), 5.24 (2H, s), 7.27-7.50 (13H, m), 10.38 (1 H, s).
71%	With potassium carbonate In acetonitrile Reflux;	6.a 2,5-bis(benzyloxy)benzaldehyde 2,5-Dihydroxybenzaldehyde 601 (3.267g, 23.65 mmol) and potassium carbonate (7.192g, 52.04 mmol, 2.2 eq) were suspended in MeCN (40 mL), with stirring. BnBr (4.045g, 2.813 mL, 23.65 mmol, 1 eq) was added and then mixture heated under reflux for 1 .5 hours. TLC analysis (eluent EtOAc/petroleum ether 40-60 3:7) showed the presence of starting aldehyde, so a further 0.1 eq of BnBr was added and the mixture stirred at 60 °C overnight. A further 0.1 eq of BnBr was added after overnight stirring. And after a further 1 hour of heating under reflux a final 0.1 eq of BnBr was added. Further heating under reflux for an hour was allowed before cooling and removal of solvent under reduced pressure to give a crude black solid. Attempts to partition the crude mixture between DCM (30 mL) and aq 1 M HCI (30 mL) caused formation of a black emulsion. Attempts to break the emulsion by adding excess organic solvent were unsuccessful, so the mixture was shaken with celite and filtered, allowing separation of the layers. Concentration and purification of the crude residue by FCC (eluent EtOAc/PE 30:70) afforded 5.34 g (71 %) of Jb/'s-protected 602 as a yellow crystalline solid.
71%	With potassium carbonate In acetonitrile at 80℃;	6.a a) 2,5-bis(Benzyloxy)benzaldehyde (602) 2,5-Dihydroxybenzaldehyde 601 (3.267 g, 23.65 mmol) and potassium carbonate (7.192 g, 52.04 mmol, 2.2 eq) were suspended in MeCN (40 mL), with stirring. BnBr (4.045 g, 2.813 mL, 23.65 mmol, 1 eq) was added and then mixture heated under reflux for 1.5 hours. TLC analysis (eluent EtOAc/petroleum ether 40-60 3:7) showed the presence of starting aldehyde, so a further 0.1 eq of BnBr was added and the mixture stirred at 80° C. overnight. A further 0.1 eq of BnBr was added after overnight stirring. And after a further 1 hour of heating under reflux a final 0.1 eq of BnBr was added. Further heating under reflux for an hour was allowed before cooling and removal of solvent under reduced pressure to give a crude black solid. Attempts to partition the crude mixture between DCM (30 mL) and aq 1M HCl (30 mL) caused formation of a black emulsion. Attempts to break the emulsion by adding excess organic solvent were unsuccessful, so the mixture was shaken with celite and filtered, allowing separation of the layers. Concentration and purification of the crude residue by FCC (eluent EtOAc/PE 30:70) afforded 5.34 g (71%) of bis-protected 602 as a yellow crystalline solid.
50%	With potassium carbonate In acetone at 20℃; Reflux; Inert atmosphere;
	With potassium carbonate In acetone	8 Stage A: 2,5-Dibenzyloxybenzaldehyde EXAMPLE 8 Stage A: 2,5-Dibenzyloxybenzaldehyde A mixture of 2,5-dihydroxybenzaldehyde (5.52 g = 40 mM), benzyl bromide (9.5 ml = 80 mM) and anhydrous potassium carbonate (16.6 g = 120 mM) in anhydrous acetone (120 ml) is refluxed for 6 h and then concentrated under reduced pressure; the residue is then taken up with water and extracted with ethyl ether. The ether phases are washed with a saturated potassium carbonate and a saturated ammonium sulfate solution, anhydrated (Na2SO4) and concentrated to afford an oil. The trituration with n-hexane - diisopropylether provides 10.6 g (83%) crude 2,5-dibenzyloxybenzaldehyde as a white solid, m.p. 74-80°C.
	With potassium carbonate In dimethyl sulfoxide at 20℃;

Reference： [1]Bavo, Francesco; Pallavicini, Marco; Gotti, Cecilia; Appiani, Rebecca; Moretti, Milena; Colombo, Sara Francesca; Pucci, Susanna; Viani, Paola; Budriesi, Roberta; Renzi, Massimiliano; Fucile, Sergio; Bolchi, Cristiano [Journal of Medicinal Chemistry, 2020, vol. 63, # 24, p. 15668 - 15692]
[2]Galindo, José L.G.; MacÍas, Mariola; Molinillo, José M.G.; Muñoz-Suano, Alba; Torres, Ascensión; Varela, Rosa M.; García-Cozar, Francisco; MacÍas, Francisco A. [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 22, p. 6662 - 6668]
[3]Mu, Fanrong; Hamel, Ernest; Lee, Debbie J.; Pryor, Donald E.; Cushman, Mark [Journal of Medicinal Chemistry, 2003, vol. 46, # 9, p. 1670 - 1682]
[4]Hayashi, Ken-ichiro; Yamazoe, Atsushi; Ishibashi, Yuki; Kusaka, Naoyuki; Oono, Yutaka; Nozaki, Hiroshi [Bioorganic and Medicinal Chemistry, 2008, vol. 16, # 9, p. 5331 - 5344]
[5]Current Patent Assignee: EISAI CO LTD - EP1864980, 2007, A1 Location in patent: Page/Page column 39-40
[6]Current Patent Assignee: UNIVERSITY OF NOTTINGHAM - WO2013/121209, 2013, A1 Location in patent: Page/Page column 25
[7]Current Patent Assignee: UNIVERSITY OF NOTTINGHAM - US2015/51270, 2015, A1 Location in patent: Paragraph 0198; 0199; 0200
[8]Tanc, Muhammet; Carta, Fabrizio; Scozzafava, Andrea; Supuran, Claudiu T. [Organic and Biomolecular Chemistry, 2014, vol. 13, # 1, p. 77 - 80]
[9]Current Patent Assignee: CORVI CAMILLO - EP401517, 1990, A1
[10]Location in patent: experimental part Ma, Lei; Yang, Zhengyi; Li, Chenjing; Zhu, Zhiyuan; Shen, Xu; Hu, Lihong [Journal of Enzyme Inhibition and Medicinal Chemistry, 2011, vol. 26, # 5, p. 643 - 648]

16
[ 1194-98-5 ]
[ 109-77-3 ]
[ 303063-73-2 ]

Yield	Reaction Conditions	Operation in experiment
98%	With piperidine In ethanol at 20℃; for 0.25h;
98%	With piperidine In ethanol at 20℃; for 0.5h;
93%	With potassium hydrogencarbonate at 20℃; for 0.416667h; solid phase reaction;

92%	With mesoporous molecular sieve MCM-41 In acetonitrile at 20℃; for 2h;
92%	With 1-methyl-3-(4-sulfobutyl)-1H-imidazol-3-ium hydrogensulfate In water at 85℃; for 1h;
91%	With piperidine In methanol	1.2. General Procedure for the Synthesis of 2-Iminochromenes (1a-f) General procedure: To a solution of aromatic aldehyde (5 mmol) and malononitrile (5 mmol) in MeOH (4 mL) piperidine(30 mol %) was added. The precipitated product was filtered and washed with cold MeOH and dried under vacuum.
91%	With piperidine In methanol	4.1 General procedure for the synthesisof2-iminochromenes (1a-g) General procedure: To a solution of aromatic aldehyde (5mmol) and malononitrile(5mmol) in MeOH (4mL) piperidine (30mol%) was added. The precipitated product was filtered andwashed with cold MeOH and dried under vacuum.
90%	With piperidine In ethanol at 20℃; for 0.166667h;
88%	In ethanol; water at 20℃; for 0.166667h; Irradiation; Green chemistry;
	With sodium hydrogencarbonate at 20℃; for 4h;

Reference： [1]Volmajer, Julija; Toplak, Renata; Bittner, Shmuel; Leban, Ivan; Le Marechal, Alenka Majcen [Tetrahedron Letters, 2003, vol. 44, # 11, p. 2363 - 2366]
[2]Volmajer, Julija; Toplak, Renata; Leban, Ivan; Le Marechal, Alenka Majcen [Tetrahedron, 2005, vol. 61, # 29, p. 7012 - 7021]
[3]Location in patent: experimental part Valizadeh, Hassan; Fakhari, Ashraf [Journal of Heterocyclic Chemistry, 2009, vol. 46, # 6, p. 1392 - 1395]
[4]Location in patent: experimental part Heravi, Majid M.; Poormohammad, Nargess; Beheshtiha, Yahia Sh; Baghernejad, Bita; Malakooti, Reihaneh [Bulletin of the Chemical Society of Ethiopia, 2010, vol. 24, # 2, p. 273 - 276]
[5]Location in patent: experimental part Heravi, Majid M.; Ansari, Parvaneh; Saeedi, Mina; Karimi, Narges; Tavakoli-Hosseini, Niloofar [Bulletin of the Chemical Society of Ethiopia, 2011, vol. 25, # 2, p. 315 - 320]
[6]Koz, Gamze; Koz, Omer; Coskun, Necdet [Synthetic Communications, 2016, vol. 46, # 10, p. 909 - 915]
[7]Koz, Gamze; Koz, Ömer [Zeitschrift fur Naturforschung, B: Chemical Sciences, 2017, vol. 72, # 9, p. 647 - 653]
[8]Turki; Abid; Le Bigot; Fery-Forgues; El Gharbi [Synthetic Communications, 2004, vol. 34, # 19, p. 3553 - 3563]
[9]Yadav, Snehlata; Srivastava, Madhulika; Rai, Pratibha; Singh, Jaya; Tiwari, Kamla Prasad; Singh, Jagdamba [New Journal of Chemistry, 2015, vol. 39, # 6, p. 4556 - 4561]
[10]Fringuelli, Francesco; Piermatti, Oriana; Pizzo, Ferdinando [Synthesis, 2003, # 15, p. 2331 - 2334]

17
[ 1194-98-5 ]
[ 52-52-8 ]
[ 929602-69-7 ]

Reference： [1]European Journal of Inorganic Chemistry,2006,p. 2656 - 2670

18
[ 241127-66-2 ]
[ 1194-98-5 ]
4-[[(2,5-dihydroxyphenyl)methylene]amino]benzoic acid 1-adamantyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With sodium hydrogencarbonate In ethanol at 20℃; for 20h;
86%	In ethanol at 20℃; for 20h;	2 To a solution of 1-adamantyl-4-aminobenzoate (5 g, 18.4 mmol) in EtOH (150 mL) containing NaHCO3 (1 mg) was added 2,5-dihydroxybenzaldehyde (2.54 g, 18.4 mmol) and the resulting solution was stirred at room temperature for twenty hours. The next day the reaction mixture was concentrated in vacuo, to remove ∼50 mL of EtOH. The residual slurry was diluted with hexane (10 mL), a yellow solid separated, was collected by filtration, washed with hexane and dried to give 6.25 g (86%) of pure product as a yellow solid.
	In ethanol	1 This example describes a general method for synthesizing compounds satisfying Formula 1 where Y is either a double bond or a single bond, and R is nitrogen. A ethanolic solution comprising 10 mmol of 2,5-dihyroxybenzaldehyde, 1 mg of NaHCO3 and 15 mls ethanol is formed, 4-aminoadamantylbenzoate is then added to the solution. A solid forms and is separated from the remaining solution, washed with hexane (10 mls) and dried in vacuo to provide an imine.

Reference： [1]Kaur, Gurmeet; Narayanan, Ven L.; Risbood, Prabhakar A.; Hollingshead, Melinda G.; Stinson, Sherman F.; Varma, Ravi K.; Sausville, Edward A. [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 5, p. 1749 - 1761]
[2]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - EP1367046, 2003, A1 Location in patent: Page 22
[3]Current Patent Assignee: GOVERNMENT OF THE UNITED STATES - EP1367046, 2003, A1 Location in patent: Page 22

19
[ 1194-98-5 ]
[ 69408-81-7 ]
[ 868962-44-1 ]

Yield	Reaction Conditions	Operation in experiment
74%	In toluene; for 2h;Heating / reflux;	Example 19; - preparation of 2-[2-(dimethvlamino)ethvll-5-ff(1Z)-(2,5-dihvdroxv- phenvl)methvlene lamino }-1 H-benzofdelisoctuinoline-1,3(2H)-dione; A mixture of 200 mg <strong>[69408-81-7]amonafide</strong>, 10 mL toluene and 119 mg 2,5- dihydroxybenzaldehyde (1.2 equivalent) was refluxed for 2 hours. After cooling, toluene was evaporated under reduced pressure and the residue was submitted to a flash chromatography (Si02, eluent : CH2Cl2/MeOH 90 : 10), thus resulting in 210.2 mg (yield : 74 %) of the desired product: which was characterized by (at)H NMR (300 MHz, DMSO) as follows : 11.87 (H-17, s); 9.18 and 9.12 (H-24 and H-25) ; 8.50 (H-2, bs) ; 8.46 (H-4, bs) ; 8.44 (H-8, bs) ; 8.40 (H- 6, bs) ; 7.89 (H-7, t, J = 7.6) ; 7.16 (H-23, d, J = 2.1); 6.94 (H-21, td, J = 2.1 and 8.4); 6.90 (H-20, t, J = 9.0) ; 4.18 (H-13, t, J = 6.6), 2.55 (H-14, m) and 2.23 (H-15 and H- 16, s).

Reference： [1]Journal of Medicinal Chemistry,2007,vol. 50,p. 4122 - 4134
[2]Patent: WO2005/105753,2005,A2 .Location in patent: Page/Page column 45

20
[ 1194-98-5 ]
[ 32744-84-6 ]

Yield	Reaction Conditions	Operation in experiment
91%	With trichloroisocyanuric acid; trifluoroacetic acid In 1,2-dichloro-ethane at -40℃; for 12h;	4.1.3 Synthesis of ortho-Chlorobenzaldehyde 19 To a mixture of 2,5-dihydroxybenzaldehyde (18, 138 mg, 1 mmol) andTCCA (92.8 mg, 0.4 mmol) in DCE (15 mL) at -40 °C was added TFA (15 μL,0.2 mmol) in one portion. The resulting mixture was stirred at -40 °C for 12hours, quenched with H2O (15 mL), and extracted with DCE (3 × 20 mL). Thecombined organic extracts were washed with brine, dried over anhydroussodium sulfate, filtered, and concentrated. The residue was purified by columnchromatography over silica gel to afford ortho-chlorobenzaldehyde 19 as ayellow solid (156 mg). Yield: 91%; m.p. = 155-157 °C; 1H NMR (400 MHz,DMSO-d6): δ/ppm = 11.09 (s, 1H), 10.33 (s, 1H), 9.94 (s, 1H), 7.23 (d, 1H, J =9.0 Hz), 6.83 (d, 1H, J = 8.8 Hz). 13C NMR (100 MHz, DMSO-d6): δ/ppm =116.5, 133.3, 117.1, 120.5, 125.6, 146.1, 155.3, 194.4; IR (thin film): νmax =3270, 2779, 2719, 1635, 1498, 1359, 1240, 1154, 1097, 1045, 913 cm-1. HRMS(ESI+): m/z calcd for C7H5ClO3Na [M+Na]+: 194.9819; found: 194.9817.
20.5%	With N-chloro-succinimide In acetonitrile at 20℃; Inert atmosphere;	7.S7A Step S_7A: Synthesis of 2-chloro-3,6-dihydroxy-benzaldehyde (7A) Step S7A: Synthesis of 2-chloro-3,6-dihydroxy-benzaldehyde (7A) 2,5-dihydroxy-benzaldehyde (100g, 0.725mol) was dissolved in MeCN (1L). To the solution was added NCS (N-chlorosuccinimide, 106g, 1.1 eq) in batches under N2 protection. After addition completed, the mixture was stirred at room temperature overnight. TLC monitored the reaction. After the reaction completed, NaHSO3(38%, 500mL) was added to the mixture, then extracted with ethyl acetate (3600mL). The organic layer was washed with water (2600mL) and brine (600mL), dried over anhydrous MgSO4, concentrated to give a crude product, which was recrystallized to give the desired product 7A (25.6g, 20.5% yield), as a yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ 11.09 (s, 1H), 10.34 (s, 1H), 9.94 (s, 1H), 7.23 (d, J = 9.2 Hz, 1H), 6.84 (d, J = 8.8 Hz, 1H).
20.5%	With N-chloro-succinimide In acetonitrile at 20℃; Inert atmosphere;	7.s.7A Step S_7A: Synthesis of 2-chloro-3,6-dihydroxy-benzaldehyde (7A) Step S7A: Synthesis of 2-chloro-3,6-dihydroxy-benzaldehyde (7A) 2,5-dihydroxy-benzaldehyde (100 g, 0.725 mol) was dissolved in MeCN (1L). To the solution was added NCS(N-chlorosuccinimide, 106 g, 1.1 eq) in batches under N2 protection. After addition completed, the mixture was stirred at room temperature overnight. TLC monitored the reaction. After the reaction completed, NaHSO3(38%, 500 mL) was added to the mixture, then extracted with ethyl acetate (3600 mL) The organic layer was washed with water (2600 mL) and brine (600 mL), dried over anhydrous MgSO4, concentrated to give a crude product, which was recrystallized to give the desired product 7A (25.6 g, 20.5% yield), as a yellow solid. 1H-NMR (400 MHz, DMSO-d6): δ 11.09 (s, 1H), 10.34 (s, 1H), 9.94 (s, 1H), 7.23 (d, J=9.2 Hz, 1H), 6.84 (d, J=8.8 Hz, 1H).

Multi-step reaction with 2 steps 1: Ag₂O; magnesium sulfate / CH₂Cl₂ 2: hydrogen chloride / CH₂Cl₂ / 20 °C

Reference： [1]Wang, Hong-Shuang; Li, Hui-Jing; Wang, Long-Fei; Shen, Zhi-Lun; Wu, Yan-Chao [Natural Product Research, 2019, vol. 33, # 13, p. 1891 - 1896]
[2]Current Patent Assignee: SHANGHAI TANGRUN PHARMACEUTICALS - EP2740734, 2014, A1 Location in patent: Paragraph 0060; 0061
[3]Current Patent Assignee: SHANGHAI TANGRUN PHARMACEUTICALS - US2014/163219, 2014, A1 Location in patent: Paragraph 0147-0149
[4]Valderrama, Jaime A.; Zamorano, Carlos; Gonzalez, M. Florencia; Prina, Eric; Fournet, Alain [Bioorganic and Medicinal Chemistry, 2005, vol. 13, # 13, p. 4153 - 4159]

21
[ 1194-98-5 ]
[ 20200-73-1 ]

Reference： [1]Synthesis,1997,p. 1137 - 1139

22
[ 110-87-2 ]
[ 1194-98-5 ]
2-hydroxy-5-tetrahydropyran-2-yloxybenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃;	2-Hydroxy-5-((tetrahydro-2H-pyran-2-yl)oxy)benzaldehyde (11): A solution of aldehyde10 (276 mg, 2.00 mmol), 2,3-dihydro-4H-pyran (841 mg, 10.00 mmol, 5 equiv.) and pyridinium p-toluenesulfonate (100 mg, 0.40 mmol, 20 mol%) in CH2Cl2 (10 mL) was stirred at ambient temperature until the starting material was completely consumed. After addition of brine the aqueous layer was extracted three times with MTBE (50 mL for each extraction), and the combined organic layers were dried with MgSO4, filtered and concentrated under reduced pressure. The residue was purified by column chromatography on silica to give 11 (444 mg,2.00 mmol, quant.). 1H NMR (300 MHz, C6D6) δ 11.19 (s, 1H), 9.14 (s, 1H), 7.02 (dd, J = 9.0,3.0 Hz, 1H), 6.90 (d, J = 2.9 Hz, 1H), 6.79 (d, J = 9.0 Hz, 1H), 5.05 (t, J = 2.9 Hz, 1H), 3.70(td, J = 10.8, 2.9 Hz, 1H), 3.36 (dt, J = 10.6, 3.4 Hz, 1H), 1.83 - 1.16 (m, 6H); 13C NMR (75MHz, C6D6) δ 196.2, 157.3, 150.3, 127.2, 120.7, 119.8, 118.6, 97.2, 61.5, 30.6, 25.5, 18.8; IR(ATR) ν 2945 (m), 1659 (s), 1482 (s), 1270 (s), 1036 (m); HRMS (EI) calcd. for C12H14O4+[M+]: 222.0892, found: 222.0888.
95%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃; for 18h;	Step 1 Step 1; To a solution of 2,5-dihydroxybenzaldehyde (5.33 g, 38.59 mmol) and pyridinium p- toluenesulfonate (0.97 g, 3.86 mmol) in DCM (165 mL) was added 3,4-dihydro-2H-pyran (3.8 mL, 41 .68 mmol) dropwise. The reaction was stirred for 18 hrs, diluted with DCM (150 mL), washed sat. aq. NaHC03 (250 mL)/brine (50 mL), dried (Na2S04), filtered and concentrated in vacuo. The aqueous layer was extracted with EtOAc (400 mL), dried (Na2S04), filtered and concentrated in vacuo. The combined organic residues were purified by flash column chromatography (0-10% EtOAc/Hept) to provide 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde (8.17 g, 95% yield) as a yellow solid. LCMS (ES+, Short): RT 1.66 min, m/z 223.2 [M+H]+ NMR (400MHz, CDCb) δ: 10.69 (1 H, s), 9.84 (1 H, d, J=0.5 Hz), 7.28-7.24 (2H, m), 6.94-6.90 (1 H, m), 5.34 (1 H, t, J=3.3 Hz), 3.95-3.87 (1 H, m), 3.66-3.59 (1 H, m), 2.04-1.93 (1 H, m), 1.90-1 .83 (2H, m), 1 .76-1.60 (3H, m).
89%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃;	2.1 Step 1 - 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde To a solution of 2,5-dihydroxybenzaldehyde (400g, 2.90mol) and pyridinium p- toluenesulfonate (36.4g, 144.8mmol) in DCM (7.5L) was added 3,4-dihydro-2H-pyran (396.3mL, 4.34mol) dropwise over 10 minutes and the reaction stirred at 30°C overnight. The reaction was washed with water (1.5L), the organic layer separated and passed through a 1.5Kg silica pad, which was washed with DCM (2.5L), 25% EtOAc in petroleum ether (2.5L) and finally 50% EtOAc in petroleum ether (2.5L). Fractions containing the product were combined and the solvent removed in vacuo. The residue was slowly diluted with petroleum ether (1.75L) and cooled to 10°C to give a thick slurry. The product was filtered, washed with petroleum ether (2x150mL) and dried to give 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde (570.7g, 2.57mol, 89% yield) as a yellow solid. UPLC-MS (ES+, Short acidic): 1.64 min, m/z 223.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ/ppm: 10.35 (1H, s), 10.23 (1H, s), 7.32-7.19 (2H, m), 6.94 (1H, d, J = 8.9Hz), 5.36 (1H, t, J = 3.3Hz), 3.77 (1H, ddd, J = 11.2Hz, 8.8Hz, 3.6Hz), 3.59-3.49 (1H, m), 1.94-1.45 (6H, m).

89%	With pyridinium 4-toluenesulfonate In dichloromethane at 20℃;	2.1 Step 1 - 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde To a solution of 2,5-dihydroxybenzaldehyde (400g, 2.90mol) and pyridinium p- toluenesulfonate (36.4g, 144.8mmol) in DCM (7.5L) was added 3,4-dihydro-2H-pyran (396.3mL, 4.34mol) dropwise over 10 minutes and the reaction stirred at 30°C overnight. The reaction was washed with water (1.5L), the organic layer separated and passed through a 1.5Kg silica pad, which was washed with DCM (2.5L), 25% EtOAc in petroleum ether (2.5L) and finally 50% EtOAc in petroleum ether (2.5L). Fractions containing the product were combined and the solvent removed in vacuo. The residue was slowly diluted with petroleum ether (1.75L) and cooled to 10°C to give a thick slurry. The product was filtered, washed with petroleum ether (2x150mL) and dried to give 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde (570.7g, 2.57mol, 89% yield) as a yellow solid. UPLC-MS (ES+, Short acidic): 1.64 min, m/z 223.0 [M+H]+.1H NMR (400 MHz, DMSO-d6) δ/ppm: 10.35 (1H, s), 10.23 (1H, s), 7.32-7.19 (2H, m), 6.94 (1H, d, J = 8.9Hz), 5.36 (1H, t, J = 3.3Hz), 3.77 (1H, ddd, J = 11.2Hz, 8.8Hz, 3.6Hz), 3.59-3.49 (1H, m), 1.94-1.45 (6H, m).
82%	With pyridinium 4-toluenesulfonate In dichloromethane at 30℃; for 2.16667h;	3.A.1; 4.A.1 Step 1 To a solution of 2,5-dihydroxybenzaldehyde (200 g, 1448 mmol) and pyridinium p-toluenesulfonate (18.2 g, 72.4 mmol) in DCM (3.75 L) was added 3,4-dihydro-2H-pyran (165 mL, 1810 mmol) dropwise over 10 minutes and the reaction temperature warmed to 30 °C. The reaction was stirred for 2 hours and checked by UPLC-MS which indicated the reaction was 92% complete (~5% starting material and ~3% later running unknown). The reaction was stopped. The reaction was washed with water (1.5 L) and the DCM solution was passed through a 750g silica pad and followed through by DCM (2.5 L). The DCM solution was reduced in-vacuo and the crude product was then slowly diluted with Pet. Ether to ~1L total volume, stirred and cooled to -10° C to afford a thick yellow slurry. The product was filtered and washed with Pet. Ether (2 x 150 mL) and pulled dry for 3 hours to afford 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde (265g, 1192 mmol, 82% yield) as a bright yellow solid. NMR (400 MHz, DMSO-d6) d/ppm: 10.35 (s, 1H), 10.23 (s, 1H), 7.32 - 7.19 (m, 2H), 6.94 (d, J = 8.9 Hz, 1H), 5.36 (t, J = 3.3 Hz, 1H), 3.77 (ddd, J = 11.2, 8.8, 3.6 Hz, 1H), 3.59 - 3.49 (m, 1H), 1.94 - 1.45 (m, 6H). UPLC-MS (ES+, Short acidic): 1.64 min, m/z 223.0 [M+H]+ (100%).
82%	With pyridinium 4-toluenesulfonate In dichloromethane at 30℃; for 2.16667h;	3.A.1; 4.A.1 Step 1 To a solution of 2,5-dihydroxybenzaldehyde (200 g, 1448 mmol) and pyridinium p-toluenesulfonate (18.2 g, 72.4 mmol) in DCM (3.75 L) was added 3,4-dihydro-2H-pyran (165 mL, 1810 mmol) dropwise over 10 minutes and the reaction temperature warmed to 30 °C. The reaction was stirred for 2 hours and checked by UPLC-MS which indicated the reaction was 92% complete (~5% starting material and ~3% later running unknown). The reaction was stopped. The reaction was washed with water (1.5 L) and the DCM solution was passed through a 750g silica pad and followed through by DCM (2.5 L). The DCM solution was reduced in-vacuo and the crude product was then slowly diluted with Pet. Ether to ~1L total volume, stirred and cooled to -10° C to afford a thick yellow slurry. The product was filtered and washed with Pet. Ether (2 x 150 mL) and pulled dry for 3 hours to afford 2-hydroxy-5-tetrahydropyran-2-yloxy-benzaldehyde (265g, 1192 mmol, 82% yield) as a bright yellow solid. NMR (400 MHz, DMSO-d6) d/ppm: 10.35 (s, 1H), 10.23 (s, 1H), 7.32 - 7.19 (m, 2H), 6.94 (d, J = 8.9 Hz, 1H), 5.36 (t, J = 3.3 Hz, 1H), 3.77 (ddd, J = 11.2, 8.8, 3.6 Hz, 1H), 3.59 - 3.49 (m, 1H), 1.94 - 1.45 (m, 6H). UPLC-MS (ES+, Short acidic): 1.64 min, m/z 223.0 [M+H]+ (100%).
	In dichloromethane at 20℃;	A solution of 2, 5-dihydroxy-benzaldehyde (152 mmol), 3, 4-dihydro-2H-pyran (167 mmol) and a catalytic amount of pyridinium p-toluenesulfonate in CH2CI2 (480 mL) was left overnight at room temperature. The organic phase was washed with 1 N Na2CO3 (aq) (3 x 100 mL) and dried (Na2504). Evaporation in vacuo gave the desired product as brown crystals that was used without further purification. 1H-NMR (CDCl3) 6 10.72 (s, 1H), 9.88 (s, 1H), 7.32-7. 29 (m, 2H), 6.96 (d, 1H), 5.38 (bs, 1H), 3.99-3. 91 (m, 1H), 3.69-3. 64 (m, 1H), 2.06-1. 63 (m, 6H).

Reference： [1]Schmidt, Bernd; Riemer, Martin; Schilde, Uwe [Synlett, 2014, vol. 25, # 20, p. 2943 - 2946]
[2]Current Patent Assignee: JAZZ PHARMACEUTICALS PLC - WO2016/38389, 2016, A1 Location in patent: Paragraph 00160; 00161
[3]Current Patent Assignee: JAZZ PHARMACEUTICALS PLC; REDX PHARMA PLC - WO2022/23447, 2022, A2 Location in patent: Paragraph 0248-0250
[4]Current Patent Assignee: JAZZ PHARMACEUTICALS PLC; REDX PHARMA PLC - WO2022/23447, 2022, A2 Location in patent: Paragraph 0248-0250
[5]Current Patent Assignee: REDX PHARMA PLC; JAZZ PHARMACEUTICALS PLC - WO2022/23450, 2022, A1 Location in patent: Paragraph 0402-0404; 0437-0440
[6]Current Patent Assignee: REDX PHARMA PLC; JAZZ PHARMACEUTICALS PLC - WO2022/23450, 2022, A1 Location in patent: Paragraph 0402-0404; 0437-0440
[7]Current Patent Assignee: LICA PHARMACEUTICALS - WO2003/97574, 2003, A2 Location in patent: Page/Page column 39

23
[ 1194-98-5 ]
triethyl-(trans-4-pentylcyclohexynecarbonyl)ammonium [ No CAS ]
[ 38289-29-1 ]
[ 83883-26-5 ]
2-[4-(6-acryloyloxyhexyloxy)benzoyloxy]-5-(4-trans-pentylcyclohexanecarbonyloxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With dmap; triethylamine; In tetrahydrofuran; THF(35 ml); ethanol; dichloromethane;	1) 2-[4-(6-Acryloyloxyhexyloxy)benzoyloxy]-5-(4-trans-pentylcyclohexanecarbonyloxy)benzaldehyde A solution of mesyl chloride (1.14 g) in 10 ml of dry THF is dropwise added to a cooled (-40 to -25°C) solution of 4-(6-acryloyloxyhexyloxy)benzoic acid (2.78 g) and triethylamine (6 ml) in 40 ml of dry THF and under argon. After complete addition (15 min), the reaction mixture was further stirred for 60 min at -25 °C then treated with a solution of 2,5-dihydroxybenzaldehyde (1.38 g) in 10 ml of dry THF and the reaction mixture is further stirred at -25°C for 2 h. This mixture was then treated with a suspension of triethyl-(trans-4-pentylcyclohexynecarbonyl)ammonium; chloride (prepared from trans-4-pentylcyclohexanecarboxylic acid (2.26 g), triethylamine (6 ml) and mesyl chloride (1.14 g) in THF(35 ml)) in dry THF (35 ml), followed by one-crop addition of DMAP (0.24 g). Stirring is continued for 3 h at -25°c and for 30 min at room temperature. The reaction mixture is then poured into 80 ml of saturated NaHCO3, extracted with 2 x 100 ml of ether. The combined organic extracts are washed with HCl 3N (100 ml) then with half saturated NaCl solution (2 x 100 ml), dried over MgSO4, filtered and evaporated to dryness to afford a slightly yellow pasty material. This is flash chromatographed over a short silica-gel column (CH2Cl2). The obtained white residue (2.3 g) was dissolved in CH2Cl2 (5 ml) then reprecipitated from ethanol (50 ml). This affords pure 2-[4-(6-acryloyloxyhexyloxy)benzoyloxy]-5-(4-trans-pentylcyclohexanecarbonyloxy)benzaldehyde as white crystalline material. Yield 1.3 g.

Reference： [1]Patent: EP1102741,2003,B1

24
[ 54-85-3 ]
[ 1194-98-5 ]
[ 863014-04-4 ]

Yield	Reaction Conditions	Operation in experiment
80%	With acetic acid In ethanol at 140℃; for 0.75h; Microwave irradiation;	4.2 General procedure for the synthesis of compounds 1a-o General procedure: A mixture of isoniazid (1.0mmol), the respective aldehyde (1.0mmol) and one drop of glacial acetic acid in ethanol (6mL) was magnetic stirred under microwave irradiation for 45min (140°C, 1000rpm). The reaction mixture was filtered off and the solid was recrystallized with ethanol. The synthesis pathway is shown on scheme 1.
	With formic acid In dimethyl sulfoxide

Reference： [1]Henriques, Ruan Roberto; Junior, Marcos Antonio de Abreu Lopes; Nogueira, Thayssa Lisboa do Couto; Romeiro, Nelilma Correia; Silva, Leandro Louback da; Farias, André Borges; Quimas, João Victor Fernandes; Santos, Daniela Corrêa; Souza, Andréa Luzia Ferreira de [Bioorganic and medicinal chemistry, 2020]
[2]Hanna, M. Leslie; Tarasow, Theodore M.; Perkins, Julie [Bioorganic Chemistry, 2007, vol. 35, # 1, p. 50 - 58]

25
[ 1194-98-5 ]
[ 5448-47-5 ]
N’-(2,5-dihydroxybenzylidene)-2-(1H-indol-3-yl)acetohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With formic acid In dimethyl sulfoxide
	With acetic acid In methanol	4.2. General procedure for the synthesis of indolederivatives (1-22) General procedure: Indole derivatives were synthesized by refluxing methyl 2-(1H-indol-3-yl) acetate (5 mmol) with hydrazine hydrate (5 mL) in methanol (15 mL) for 6 hrs yielded 2-(1H-indol-3-yl)acetohydrazide as intermediate product (I). The completionof reaction was monitored using TLC. The excess solventwere evaporated under vacuum to obtain the crude productand recrystallized in methanol to obtained pure product.Equimolar intermediate product (I) then further treated withdifferent aldehydes (1-22) in methanol (15 mL) for 3-4 hrs inthe presence of catalytic amount of acetic acid yieldedindole derivatives (1-22). The completion of reaction wasmonitored with the help of TLC. The crude was then recrystallizedin methanol to obtained pure product (Hanna et al.,2007; Ju et al., 2019; Liu et al., 2019; Mirfazli et al., 2016).

Reference： [1]Hanna, M. Leslie; Tarasow, Theodore M.; Perkins, Julie [Bioorganic Chemistry, 2007, vol. 35, # 1, p. 50 - 58]
[2]Taha, Muhammad; Ismail, Sukinah; Imran, Syahrul; Almandil, Noor Barak; Alomari, Munther; Rahim, Fazal; Uddin, Nizam; Hayat, Shawkat; Zaman, Khalid; Ibrahim, Mohamad; Alghanem, Bandar; Islam, Imadul; Farooq, Rai Khalid; Boudjelal, Mohamed; Khan, Khalid Mohammed [Journal of Biomolecular Structure and Dynamics, 2021]

26
[ 1194-98-5 ]
[ 39635-11-5 ]
[ 929684-83-3 ]

Reference： [1]Bioorganic Chemistry,2007,vol. 35,p. 50 - 58

27
[ 1194-98-5 ]
[ 136-64-1 ]
C₂₂H₁₈N₄O₆ [ No CAS ]

Reference： [1]Bioorganic Chemistry,2007,vol. 35,p. 50 - 58

28
[ 1194-98-5 ]
[ 16632-21-6 ]
[ 1173698-50-4 ]

Reference： [1]Journal of Organic Chemistry,2009,vol. 74,p. 5123 - 5134
[2]Chemical Biology and Drug Design,2015,vol. 85,p. 296 - 299

29
[ 1194-98-5 ]
[ 23489-36-3 ]
[ 1208448-93-4 ]

Yield	Reaction Conditions	Operation in experiment
78%	With potassium carbonate In acetonitrile at 90℃; for 18h; Reflux; Inert atmosphere;	To a solution of 2,5-dihydroxybenzaldehyde (86 mg, 0.62 mmol)and K2CO3 (85 mg, 0.62 mmol) in CH3CN (5 ml) was added l-(benzofuran-2-yl)-2-bromoethanone (60 μl, 0.62 mmol) in portions. The reaction flask was then fitted with a reflux condenser and the solution was heated to 90 0C. The reaction was stirred at reflux, under nitrogen atmosphere, for 18 h. The reaction was allowed to cool to room temperature and the reaction mixture was diluted with CH2Cl2 (20 ml). The solid salts were filtered off and the filtrate reduced under vacuum. The product was purified by column chromatography, eluting with n - hexane: AcOEt (9:1). Further purification by recrystallization from EtOH yielded benzofuran- 2-yl(5-hydroxybenzofuran-2-yl)methanone (135 mg, 78%) as a white solid.

Reference： [1]Current Patent Assignee: YALE UNIVERSITY - WO2010/21693, 2010, A2 Location in patent: Page/Page column 40

30
[ 1194-98-5 ]
[ 6011-14-9 ]
[ 1279019-04-3 ]

Yield	Reaction Conditions	Operation in experiment
65%	With sodium acetate; In methanol; at 20℃; for 2h;	General procedure: 2-Aminoacetonitrile hydrochloride 2 (7.0 mmol) and sodium acetate (8.0 mmol) were dissolved in 35 mL of methanol. Aldehyde 1 (7.0 mmol) was added to the grey solution, and the reaction mixture was stirred at room temperature. A solid suspension was formed after a few minutes (for compounds 3a, 3c, 3f and 3g). The suspension was stirred for 2 h and the solid filtered and washed with cold methanol, leading to the pure product 3. A second crop was isolated from the mother liquor after complete removal of methanol in the rotary evaporator, addition of dichloromethane (40 mL) and dry flash chromatography of the solution using dichloromethane (4×10 mL) as eluent. The solution was concentrated in the rotary evaporator and the yellow oil was kept at 0 C leading to the product 3 that was filtered and washed with cold diethyl ether. For compounds 3b, 3d, 3e and 3h-k, the reaction mixture was stirred at room temperature for 2 h. The solvent was removed in the rotary evaporator and dichloromethane (40 mL) was added to the mixture. Dry flash chromatography of this mixture was performed using 20 mL of dichloromethane as eluent. The solvent was removed in the rotary evaporator leading to a solid product. Cold diethyl ether was added to the suspension, kept for a few minutes in an ice bath. The solid was filtered and washed with cold diethyl ether, leading to the pure (arylideneamino)acetonitrile 3.

Reference： [1]Tetrahedron,2011,vol. 67,p. 1799 - 1804

31
[ 1194-98-5 ]
[ 137-07-5 ]
[ 24978-47-0 ]

Yield	Reaction Conditions	Operation in experiment
99%	With yttrium(III) chloride In ethanol for 0.5h; Reflux; Green chemistry;	A general procedure for preparation of dihydropyrazines 3 General procedure: YCl3(0.0098 g, 0.05 mmol) were dissolved in 10mL EtOH and stirred until the soliddissolved completely in refluxing, then 2-aminobenzenethiols 1a (0.118 mL, 1.1mmol) and benzaldehyde 2a (0.101 ml, 1.0 mmol) was added into thereaction mixture. After 30min, TLC showed the reaction to be complete. Thereaction mixture was cooled to r.t., and then evaporated in vacuum. The productpurified by column chromatography (PE-EtOAc= 20:1) to give white solid 3a(0.2092 g, 99%)
87%	With silver nitrate In dimethyl sulfoxide at 20℃;
72%	With sodium metabisulfite In N,N-dimethyl-formamide for 2h; Reflux;	2.2.1. 2-benzothiazole-2-benzobenzene-1,4-diol (BTBD) 2-aminothiophenol (500 mg, 3.99 mmol) and 2,5-dihydroxybenzaldehyde (580 mg, 4.2 mmol) were dissolved in DMF (20 mL) and add Na2S2O5 (0.70 g, 4.20mmol) with continuous stirring.The reaction mixture was refluxed for 2 h, and the reaction was monitoredby TLC. After the reaction was completed, it was cooled to roomtemperature, and water (50 mL) was added. Solid precipitate was collectedon a filter and recrystallized frommethanol to give the pure productBTBD (702 mg, 72% yield). 1H NMR (600MHz, DMSO d6): δ 10.84 (t,J=3.0 Hz, 1H), 9.17 (t, J=3.1 Hz, 1H), 8.12 (dt, J=7.1, 2.6 Hz, 1H), 8.00(dd, J=7.6, 3.1 Hz, 1H), 7.65-7.47 (m, 2H), 7.41 (dt, J=9.0, 5.6 Hz, 1H),6.91-6.88 (m, 1H), 6.83 (dq, J = 8.7, 3.4, 2.9 Hz, 1H). HRMS (ESI, m/z)calculated for [C13H9NO2S H] : 244.0432, found: 244.0427.

72%	With sodium metabisulfite In N,N-dimethyl-formamide Reflux;
58%	With sodium dithionite In ethanol; water for 12h; Reflux;	3.2.1 General method for the synthesis of 2-Arylbenzothiazoles unsubstituted on the benzothiazole ring General procedure: To a solution of 2-aminothiophenol (0.4g, 3.2mmol) and aldehyde (3.2mmol) in ethanol (3.5mL) at room temperature was added solution of sodium hydrosulfite (2eq. in 3mL H2O). The mixture was heated at reflux for 12h. After cooling to room temperature, the solution was concentrated in vacuo. The residue was treated with HCl 2N (15mL) and filtered to obtain the crude solid, which was recrystallized from appropriate solvent. Compounds 4b, 4e and 4f were synthesized with and without catalyst following the same procedure described above.
	With sodium metabisulfite In N,N-dimethyl-formamide for 2h; Reflux;	4.1. General procedure for the synthesis of compounds 1-26 In a typical procedure, benzothiazoles 1-26 were synthesized by mixing together commercially available 2-aminothiophenol (3.12 mmol) and different aromatic aldehydes (3.16 mmol) in N,N-dimethylformamide (DMF) 10 mL, sodium metabisulfite Na2S2O5 (0.61 g) was added to a stirring mixture. The reaction mixture was refluxed for 2 h and the progress of the reaction was monitored by TLC. After completion of the reaction, mixture was allowed to cool to room temperature, addition of water (30 mL), product which precipitated as a solid, after filtration afforded the benzothiazole derivatives 1-26 in high yields. Recrystallization from methanol afforded pure product.
	With sodium metabisulfite In N,N-dimethyl-formamide for 2h; Reflux;
	With sodium metabisulfite In N,N-dimethyl-formamide for 2h; Reflux;	General procedure for the synthesis of compounds 1-26 General procedure: In a typical reaction, benzothiazoles 1-26 were re-synthesized by dissolving 2-aminothiophenol (3.12mmol) and different aromatic aldehydes (3.16mmol) in DMF (10mL). Sodium metabisulfite (Na2S2O5, 0.61g) was also added to the above-mentioned solution with continuous stirring. The resulting reaction mixture was refluxed for 2h and the progress of the reaction was monitored by TLC analysis. After completion of the reaction, it was allowed to cool to room temperature and water (30mL) was added. The solid precipitated benzothiazoles (1-26) were collected on a filter and obtained in high yields. Recrystallization from methanol yielded pure products and their physical and spectroscopic data matched satisfactorily with previously reported literature values [21].
8.6 g	With sodium hydrogensulfite In N,N-dimethyl acetamide at 100℃; for 4h; Inert atmosphere;	3 The following compound (1-1-10-1) was synthesized as follows 5.0 g of 2,5-dihydroxybenzaldehyde, Aminobenzenethiol (4.5 g) and sodium hydrogen sulfite Was added to 50 mL of dimethylacetamide (DMA) And the mixture was stirred at 100°C for 4 hours under a nitrogen atmosphere. After allowing to cool, 100 mL of water was added, and the precipitate was filtered, The crystals were washed with water. The obtained crystals were recrystallized from heptane / methanol to obtain 8.6 g of compound (ex-7).

Reference： [1]Fan, Li-Yan; Shang, Ying-Hui; Li, Xiang-Xiong; Hua, Wen-Jun [Chinese Chemical Letters, 2015, vol. 26, # 1, p. 77 - 80]
[2]He, Xinwei; Wu, Yuhao; Jin, Wenjing; Wang, Xiaoshun; Wu, Cong; Shang, Yongjia [Applied Organometallic Chemistry, 2018, vol. 32, # 4]
[3]Zhu, Meiqing; Liu, Xina; Yang, Yanan; Wang, Lijun; Wu, Xiaoqin; Fan, Shisuo; Wang, Zhen; Hua, Rimao; Wang, Yi; Li, Qing X. [Journal of Molecular Liquids, 2019, vol. 287]
[4]Zhu, Meiqing; Wu, Xiaoqin; Sang, Linfeng; Fan, Fugang; Wang, Lijun; Wu, Xiangwei; Hua, Rimao; Wang, Yi; Li, Qing X. [New Journal of Chemistry, 2019, vol. 43, # 34, p. 13463 - 13470]
[5]Andreotti, Elisa; Baldisserotto, Anna; Balzarini, Jan; Buzzi, Raissa; Dissette, Valeria; Djuidje, Ernestine Nicaise; Liekens, Sandra; Manfredini, Stefano; Sciabica, Sabrina; Serra, Elena; Vertuani, Silvia [Bioorganic Chemistry, 2020, vol. 101]
[6]Location in patent: experimental part Khan, Khalid Mohammed; Rahim, Fazal; Halim, Sobia Ahsan; Taha, Muhammad; Khan, Momin; Perveen, Shahnaz; Zaheer-Ul-Haq; Mesaik, Muhammad Ahmed; Iqbal Choudhary [Bioorganic and Medicinal Chemistry, 2011, vol. 19, # 14, p. 4286 - 4294]
[7]Rahim, Fazal; Samreen; Taha, Muhammad; Saad, Syed Muhammad; Perveen, Shahnaz; Khan, Momin; Alam, Muhammad Tanveer; Khan, Khalid Mohammed; Choudhary, M. Iqbal [Journal of the Chemical Society of Pakistan, 2015, vol. 37, # 1, p. 157 - 161]
[8]Khan, Khalid Mohammed; Mesaik, Mohammad A.; Abdalla, Omer M.; Rahim, Fazal; Soomro, Samreen; Halim, Sobia A.; Mustafa, Ghulam; Ambreen, Nida; Khalid, Ahmad Shukralla; Taha, Muhammad; Perveen, Shahnaz; Alam, Muhammad Tanveer; Hameed, Abdul; Ul-Haq, Zaheer; Ullah, Hayat; Rehman, Zia Ur; Siddiqui, Rafat Ali; Voelter, Wolfgang [Bioorganic Chemistry, 2016, vol. 64, p. 21 - 28]
[9]Current Patent Assignee: CHISSO CORPORATION - KR2016/106513, 2016, A Location in patent: Paragraph 0306-0309

32
[ 1194-98-5 ]
[ 130365-87-6 ]
[ 1311393-07-3 ]

Reference： [1]Journal of Medicinal Chemistry,2011,vol. 54,p. 4490 - 4507

33
[ 1194-98-5 ]
[ 141-97-9 ]
[ 810676-15-4 ]

Yield	Reaction Conditions	Operation in experiment
93%	With zinc oxide nanoparticle at 120℃; for 0.1h; Microwave irradiation; Neat (no solvent);
93%	With ziconium(IV) oxychloride octahydrate at 20℃; for 0.333333h; Milling; Green chemistry;
93%	With piperidine In ethanol at 80℃; for 0.025h; Microwave irradiation; Green chemistry;	Synthesis of 3-Acetyl-2H-chromen-2-one (1a): General procedure: A mixture salicylaldehyde S1 (2 mmol, 0.218 mL) and ethanol (20 mL) was stirred, and ethyl acetoacetate (2.4 mmol, 0.31 mL) was later added. Then, a catalytic amount of piperidine was added and swirled thoroughly. The reaction mixtures were added together in a microwave reaction vial and irradiated in microwave oven for a specific period of time and temperature as shown in Table S2 (Scheme S1). The reaction was monitored by TLC till completion. After completion, it was then allowed to cool for few minutes in iced water bath. A solid product was formed (Fig. S1). The product was ltered and dried to afford the product whose physicochemical properties are shown in Table S2. The same procedure was followed in the synthesis of other derivatives 1b-j. Each of the spectroscopic data is in agreement with the structures assigned.

90%	With piperidine In ethanol for 24h; Reflux;
65%	With piperidine; acetic acid In ethanol for 4h; Reflux;
	With piperidine In ethanol at 50℃;	General procedure for the synthesis of 3-acetylcoumarin derivatives 8 or 10 General procedure: A cold mixture of salicylaldehyde derivative 7 or 9 (0.2 mol) and ethyl acetoacetate (0.2 mol) in absolute ethanol (25 mL) was treated with piperidine (0.2 mL). The mixture was allowed to warm to 50 °C. After completion of the reaction, the precipitated solid was filtered off and subsequently washed with ethanol and recrystallized from water-ethanol (30:70) to give pure product.
	With piperidine In ethanol at 20℃;
	With piperidine In ethanol Reflux;	Synthesis of R-coum derivatives.- General procedure: All hydroxylated coumarins(R-coum) were obtained by Knoevenagel reaction34 following thenext procedure: addition of an equimolar quantity of correspondinghydroxyl salicylaldehyde (1 mmol) and ethyl acetoacetate (1 mmol)using catalytic amounts of piperidine in ethanol (25 ml) under refluxand monitoring by thin-layer chromatography. Final products werepurified through crystallization in ethanol and structure was confirmedby 1HNMR. Figure 1 and Table I.

Reference： [1]Location in patent: experimental part Kumar, B Vinay; Naik, Halehatty S. Bhojya; Girija; Kumar, B Vijaya [Journal of Chemical Sciences, 2011, vol. 123, # 5, p. 615 - 621]
[2]Tasqeeruddin; Al-Arifi, Abdullah S.; Dubey [Asian Journal of Chemistry, 2013, vol. 25, # 12, p. 6885 - 6887]
[3]Yahaya, Issah; Seferoğlu, Nurgül; Seferoğlu, Zeynel [Tetrahedron, 2019, vol. 75, # 14, p. 2143 - 2154]
[4]Martinez-Martinez, Francisco J.; Razo-Hernandez, Rodrigo Said; Peraza-Campos, Ana Lilia; Villanueva-Garcia, Manuel; Sumaya-Martinez, Maria Teresa; Cano, Daniel Jaramillo; Gomez-Sandoval, Zeferino [Molecules, 2012, vol. 17, # 12, p. 14882 - 14898]
[5]Zerangnasrabad, Sara; Jabbari, Atena; Khavari Moghadam, Elahe; Sadeghian, Hamid; Seyedi, Seyed Mohammad [Drug Development Research, 2021, vol. 82, # 6, p. 826 - 834]
[6]Molaverdi, Fatemeh; Khoobi, Mehdi; Emami, Saeed; Alipour, Masoumeh; Firuzi, Omidreza; Foroumadi, Alireza; Dehghan, Gholamreza; Miri, Ramin; Shaki, Fatemeh; Jafarpour, Farnaz; Shafiee, Abbas [European Journal of Medicinal Chemistry, 2013, vol. 68, p. 103 - 110]
[7]Kumar, Gautam; Siva Krishna, Vagolu; Sriram, Dharmarajan; Jachak, Sanjay M. [Archiv der Pharmazie, 2020, vol. 353, # 8]
[8]Barrientos, C.; Navarrete-Encina, P.; Squella, J. A. [Journal of the Electrochemical Society, 2020, vol. 167, # 16]
[9]Šubarić, Domagoj; Agić, Dejan; Bešlo, Drago; Karačić, Zrinka; Karnaš, Maja; Lisjak, Miroslav; Lončarić, Melita; Molnar, Maja; Popović, Boris M.; Rastija, Vesna; Tomić, Sanja [Pharmaceuticals, 2021, vol. 14, # 6]

34
[ 155-90-8 ]
[ 1194-98-5 ]
[ 68-11-1 ]
2-(2,5-dihydroxyphenyl)-3-(4-methoxypyrimidin-2-yl)-thiazolidin-4-one [ No CAS ]

Reference： [1]Asian Journal of Chemistry,2012,vol. 24,p. 4317 - 4323

35
[ 1194-98-5 ]
[ 74-88-4 ]
[ 35431-26-6 ]

Yield	Reaction Conditions	Operation in experiment
57%		A mixture of 2,5-dihydroxybenzaldehyde (1 g, 7.24 mmol) andK2CO3 (1 g, 7.24 mmol) was dissolved in DMF (10 mL) and stirred atroom temperature for 30 min before methyl iodide (0.679 mL,10.9 mmol) was added. The reaction mixture was stirred at roomtemperature overnight. The solvent was evaporated in vacuum andthe crude was puried using ash-column chromatography (n-heptane/EtOAc 2:1) to gain compound 212(621 mg, 57% yield) as ayellow solid.1H-NMR (300 MHz, CDCl3) d 10.33 (s, 1H), 7.30 (d,J 3.2 Hz, 1H), 7.10 (dd, J 9.0, 3.2 Hz, 1H), 6.84 (d, J 8.9 Hz, 1H),6.70 (broad s, 1H), 3.84 (s, 3H).13C-NMR (75 MHz, CDCl3) d 190.6,156.6, 150.2, 125.0, 124.1, 113.9, 113.5, 56.2.
43%		General procedure: 2,5-Dihydroxybenzaldehyde (1.0 eq.) and cesium carbonate (1.0 eq.) were suspended in DMF and the suspension, warmed to 60 C for 15 min. After cooling down to rt, the corresponding bromide (1.1 eq.) was added in DMF (0.5 M concentration of 2,5-dihydroxybenzaldehyde) and the reaction was stirred at rt for 2h for benzylic haloalkanes or at 60 C overnight for aliphatic haloalkanes. The solvents were evaporated and the crude dissolved in water and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3x) and the combined organic layers were dried over magnesium sulfate, filtered and the solvent evaporated. The crude product was purified by flash chromatography.

Reference： [1]Tetrahedron,2017,vol. 73,p. 6393 - 6400
[2]Journal of Organic Chemistry,2016,vol. 81,p. 10922 - 10929
[3]Chemical Communications,2012,vol. 48,p. 11904 - 11906
[4]European Journal of Organic Chemistry,2018,vol. 2018,p. 5605 - 5614
[5]Bioorganic and Medicinal Chemistry,2019,vol. 27
[6]Applied Organometallic Chemistry,2015,vol. 29,p. 322 - 327

36
[ 1194-98-5 ]
[ 646-24-2 ]
[ 1416548-26-9 ]

Yield	Reaction Conditions	Operation in experiment
85%	In methanol;	General procedure: All the tetradentate Schiff base ligands were prepared by the condensation between diamines and 2,5-dihydroxybenzaldehyde in methanol. The Schiff base ligands were prepared by dissolving 2,5-dihydroxybenzaldehyde (0.35 g, 2.5 mmol) and diamine (0.1 g, 1.4 mmol) in methanol with stirring. The stirring was continued until completion of the reaction. The progress of the reaction was monitored by thin layer chromatography (TLC). After the completion of the reaction, a colored substance was obtained. The solid product was filtered off and washed with cold MeOH and the pure Schiff base was obtained in high yield after leaving the solid for the appropriate time to dry. The Schiff base products were identified by physical and spectroscopic data [18].
85%	In methanol; for 0.25h;	General procedure: Mixture of 2,5-dihydroxybenzaldehyde (0.35 g, 2.5 mmol) inMeOH was added to diamine (1.4 mmol) and stirred for 5 min.The progress of the reaction was monitored by TLC. After thereaction completion, a yellow solid product was filtered off andwashed with cold MeOH and pure Schiff base was obtained.The Schiff base products were identified by physical and spectroscopic data.

Reference： [1]Polyhedron,2013,vol. 49,p. 234 - 238
[2]Inorganic and Nano-Metal Chemistry,2017,vol. 47,p. 1480 - 1487

37
[ 1194-98-5 ]
[ 168646-54-6 ]
[ 1426233-08-0 ]

Reference： [1]Dalton Transactions,2013,vol. 42,p. 8907 - 8917

38
[ 1194-98-5 ]
[ 2491-38-5 ]
6-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
88%	Stage #1: 2-bromo-1-(4'-hydroxyphenyl)-1-ethanone With thiamine hydrochloride In ethanol at 20℃; for 0.25h; Green chemistry; Stage #2: 2,5-Dihydroxybenzaldehyde In ethanol at 20℃; for 1.41667h; Green chemistry;	Experimental General procedure: To prepare catalyst, 0.21 g of thiamine hydrochloride (0.6 mmol) was dissolved in 0.64 mL of water and added 2.4 mLof 95% ethanol (water : 95% ethanol = ~1:4). The solution was cooled in an ice bath, then added 0.40 mL of 3 M NaOH(1.2 mmol) dropwise with stirring in a manner such that thetemperature remained below 20 °C. Intense yellow coloured solution changed to pale yellow solution of thiamine (thiazolium ion)/N-heterocyclic carbene (Scheme 1).47 In a 25-mL round bottom flask, a mixture of phenacylbromide 1 (2.5 mmol, 0.5 g in case of 1a) and thiamine (0.6 mmol, 25 mol %) in ethanol (4 mL) was stirred at room temperature for 15 min. Then, salicylaldehyde 2 (2.5 mmol, 0.26 mL in case of 2a) was added slowly and the mixture was stirred at room temperature until the reaction was completed (as monitored by TLC) (Table 3) . The reaction mixture was then poured into 20 mL of distilled water and extracted with ethyl acetate (3 × 10 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was removed under reduced pressure. The resulting product isoflavone 3 was further purified either by recrystallizationor by column chromatography (Ethyl acetate:Hexane, 1:4v/v). All compounds were characterized by their mp and 1HNMR, 13CNMR and mass spectral data.

Reference： [1]Mishra, Priya; Singh, Sarita; Ankit, Preyas; Fatma, Shahin; Singh, Divya; Singh, Jagdamba [Bulletin of the Korean Chemical Society, 2013, vol. 34, # 4, p. 1070 - 1076]

39
[ 1194-98-5 ]
[ 4687-37-0 ]
[ 1456071-25-2 ]

Reference： [1]MedChemComm,2013,vol. 4,p. 993 - 1000

40
[ 1194-98-5 ]
[ 4687-37-0 ]
[ 1456071-21-8 ]

Reference： [1]MedChemComm,2013,vol. 4,p. 993 - 1000

41
[ 1194-98-5 ]
[ 14741-71-0 ]
[ 178993-72-1 ]

Reference： [1]Indian Journal of Heterocyclic Chemistry,2012,vol. 21,p. 289 - 292

42
[ 1194-98-5 ]
4-(6-acryloylhex-1-yloxy)benzoic acid [ No CAS ]
[ 171498-67-2 ]

Yield	Reaction Conditions	Operation in experiment
75.4%	With 1-methyl-pyrrolidin-2-one; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 25℃; for 12h; Flow reactor; Inert atmosphere;	1.1 Step 1: Synthesis of intermediate A [0173] A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25°C for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 1 of water, and extracted with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio)) to obtain 75 g of an intermediate A as a white solid (yield: 75.4%). [0174] The structure of the target product was identified by 1H-NMR. [0175] 1H-NMR (400 MHz, CDCl3, TMS, δ ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H).
75.4%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1-methyl-pyrrolidin-2-one at 25℃; for 12h; Inert atmosphere;	1.1 Step 1: Synthesis of Intermediate a A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC), the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, and extracted with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was separated by filtration. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1) to obtain 75 g of an intermediate a as a white solid (yield: 75.4%). [0326] The structure of the target product was identified by 1H-NMR. 1H-NMR (400 MHz, CDCl3, TMS, δ ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H)
75.4%	With 1-methyl-pyrrolidin-2-one; dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride at 25℃; for 12h; Inert atmosphere;	1.1 Step 1: Synthesis of Intermediate D A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, followed by extraction with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1) to obtain 75 g of an intermediate D as a white solid (yield: 75.4%). (0249) The structure of the target product was identified by 1H-NMR. (0250) 1H-NMR (400 MHz, CDCl3, TMS, δ ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H).

75.4%

With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In 1-methyl-pyrrolidin-2-one at 25℃; for 12h; Inert atmosphere;

2.1 Synthesis of Intermediate E A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, followed by extraction with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1) to obtain 75 g of an intermediate E as a white solid (yield: 75.4%). (0231) The structure of the target product was identified by 1H-NMR. (0232) 1H-NMR (400 MHz, CDCl3, TMS, δ ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H)

Reference： [1]Current Patent Assignee: ZEON CORPORATION - EP2703385, 2014, A1 Location in patent: Paragraph 0173
[2]Current Patent Assignee: ZEON CORPORATION - US2015/175564, 2015, A1 Location in patent: Paragraph 0324; 0325
[3]Current Patent Assignee: ZEON CORPORATION - US2015/274647, 2015, A1 Location in patent: Paragraph 0247-0250
[4]Current Patent Assignee: ZEON CORPORATION - US2016/257659, 2016, A1 Location in patent: Paragraph 0230-0232

43
[ 1194-98-5 ]
[ 304-20-1 ]
[ 1583268-11-4 ]

Yield	Reaction Conditions	Operation in experiment
76.4%	With camphor-10-sulfonic acid; In ethanol; at 25℃; for 3h;Flow reactor; Inert atmosphere;	A four-necked reactor equipped with a thermometer was charged with 394 mg (2.85 mmol) of 2,5-dihydroxybenzaldehyde, 562 mg (2.86 mmol) of 1-hydrazinophthalazine hydrochloride, 65 mg (0.28 mmol) of (±)-10-camphorsulfonic acid, and 20 ml of ethanol under a nitrogen stream. The mixture was stirred at 25C for 3 hours. After completion of the reaction, a solid that had precipitated was filtered off. The solid was washed with ethanol, and dried using a vacuum dryer to obtain 610 mg of an intermediate C as a yellow solid (yield: 76.4%). [0200] The structure of the target product was identified by 1H-NMR. [0201] 1H-NMR (500 MHz, DMSO-d6, TMS, delta ppm): 14.486 (br, 1H), 14.150 (br, 1H), 9.77 (s, 1H), 9.30 (s, 1H), 9.20 (d, 1H, J=8.0 Hz), 9.06 (s, 1H), 8.27-8.14 (m, 3H), 7.76 (d, 1H, J=2.5 Hz), 6.89 (dd, 1H, J=3.0 Hz, 8.5 Hz), 6.84 (d, 1H, J=8.5 Hz).
76.1%	With 10-camphorsufonic acid; In ethanol; at 25℃; for 2h;Inert atmosphere;	A four-necked reactor equipped with a thermometer was charged with 197 mg (1.43 mmol) of 2,5-dihydroxybenzaldehyde, 281 mg (1.43 mmol) of 1-hydrazinophthalazine hydrochloride, 32.5 mg (0.14 mmol) of (±)-10-camphorsulfonic acid, and 10 ml of ethanol under a nitrogen stream. The mixture was stirred at 25C for 2 hours. After completion of the reaction, a solid precipitate was filtered off. The solid collected by filtration was washed with ethanol, and dried using a vacuum dryer to obtain 305 mg of a compound (I-10) as a yellow solid (yield: 76.1%). [0150] The structure of the target product was identified by 1H-NMR. [0151] The 1H-NMR spectrum data are shown below. [0152] 1H-NMR (500 MHz, DMSO-d6, TMS, delta ppm): 14.486 (br, 1H), 14.150 (br, 1H), 9.77 (s, 1H), 9.30 (s, 1H), 9.20 (d, 1H, J=8.0 Hz), 9.06 (s, 1H), 8.27-8.14 (m, 3H), 7.76 (d, 1H, J=2.5 Hz), 6.89 (dd, 1H, J=3.0 Hz, 8.5 Hz), 6.84 (d, 1H, J=8.5 Hz)

Reference： [1]Patent: EP2703385,2014,A1 .Location in patent: Paragraph 0199
[2]Patent: EP2762465,2014,A1 .Location in patent: Paragraph 0148-0152

44
[ 1118-66-7 ]
[ 1194-98-5 ]
4-acetyl-3-methylisoquinoline-5,8-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With magnesium sulfate; silver(l) oxide; In dichloromethane; at 20℃; for 4h;	A suspension of 2,5-dihydroxybenzaldehyde (1a,1 mmol), <strong>[1118-66-7]4-aminopent-3-en-2-one</strong> (2b, 1 mmol), Ag2O (2 mmol) and MgSO4 (0.5 g) in CH2Cl2 (25 mL) was stirred at rt for 3.15 h. The mixture was filtered, the solids were washed with CH2Cl2 andthe solvent removed under reduced pressure. The residue was column chromatographed over silica gel (90:10 CH2Cl2/EtOAc) to yield pure quinone 4a (74%) as an orange solid,

Reference： [1]Molecules,2014,vol. 19,p. 726 - 739

45
[ 1194-98-5 ]
[ 83883-26-5 ]
[ 171498-67-2 ]

Yield	Reaction Conditions	Operation in experiment
75.4%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere;	A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25°C for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, and extracted with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio)) to obtain 75 g of an intermediate A as a white solid (yield: 75.4percent). [0160] The structure of the target product was identified by 1H-NMR. [0161] 1H-NMR data for intermediate A 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H).
75.4%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere;	A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde,105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g(43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare ahomogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimidehydrochloride (WSC) to the solution, the mixture was stirred at 25°C for 12 hours.[0169] After completion of the reaction, the reaction mixture was added to 1.51 of water, and extracted with 500 ml ofethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethylacetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid.The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio)) toobtain 75 g of an intermediate A as a white solid (yield: 75.4percent). The structure of the target product was identified by 1HNMR.[0170] 1H-NMR data for intermediate A1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H),1.58-1.42 (m, 8H).
75.4%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere;	Step 3: Synthesis of Intermediate C A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a homogeneous solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (hereinafter referred to as ?WSC?) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, and extracted with 500 ml of ethyl acetate. After drying the ethyl acetate layer over anhydrous sodium sulfate, sodium sulfate was separated by filtration. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1 (volume ratio (hereinafter the same))) to obtain 75 g of an intermediate C as a white solid (yield: 75.4percent). The structure of the target product was identified by 1H-NMR. 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H)

75.4%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 25℃; for 12h;Inert atmosphere;	Step 1: Synthesis of Intermediate E (0199) (0200) A four-necked reactor equipped with a thermometer was charged with 20 g (144.8 mmol) of 2,5-dihydroxybenzaldehyde, 105.8 g (362.0 mmol) of 4-(6-acryloylhex-1-yloxy)benzoic acid (manufactured by DKSH Japan K.K.), 5.3 g (43.4 mmol) of 4-(dimethylamino)pyridine, and 200 ml of N-methylpyrrolidone under a nitrogen stream to prepare a solution. After the addition of 83.3 g (434.4 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) to the solution, the mixture was stirred at 25° C. for 12 hours. After completion of the reaction, the reaction mixture was added to 1.5 l of water, followed by extraction with 500 ml of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. Ethyl acetate was evaporated from the filtrate under reduced pressure using a rotary evaporator to obtain a light yellow solid. The light yellow solid was purified by silica gel column chromatography (toluene:ethyl acetate=9:1) to obtain 75 g of an intermediate E as a white solid (yield: 75.4percent). (0201) The structure of the target product was identified by 1H-NMR. (0202) 1H-NMR (400 MHz, CDCl3, TMS, delta ppm): 10.20 (s, 1H), 8.18-8.12 (m, 4H), 7.78 (d, 1H, J=2.8 Hz), 7.52 (dd, 1H, J=2.8 Hz, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.00-6.96 (m, 4H), 6.40 (dd, 2H, J=1.4 Hz, 17.4 Hz), 6.12 (dd, 2H, J=10.6 Hz, 17.4 Hz), 5.82 (dd, 2H, J=1.4 Hz, 10.6 Hz), 4.18 (t, 4H, J=6.4 Hz), 4.08-4.04 (m, 4H), 1.88-1.81 (m, 4H), 1.76-1.69 (m, 4H), 1.58-1.42 (m, 8H)
75 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In 1-methyl-pyrrolidin-2-one; at 20℃; for 12h;Inert atmosphere;	2,5-dihydroxybenzaldehyde 20 g (144.8 mmol) in a 4-port reactor equipped with a thermometer under a nitrogen stream. 4-(6-Propyloxy-1-hexyloxy)benzoic acid (manufactured by DKSH Co., Ltd.) 105.8 g (362.0 mmol), N,N-dimethylaminopyridine (N,N-dimethyl-4) -Aminopyridine) 5.3 g (43.4 mmol) was dissolved in 200 mL of N-methylpyrrolidone (N-methyl-2-pyrrolidone). 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSC) 83.3 g (434.4 mmol) was added to this solution, and stirred at room temperature for 12 hours. After completion of the reaction, the reaction solution was poured into 1.5 L of water and extracted with ethyl acetate (500 mL). The ethyl acetate layer was dried over anhydrous sodium sulfate. After the sodium sulfate was filtered off, ethyl acetate was evaporated to dryness eluted from the filtrate to give a pale yellow solid. The pale yellow solid was purified by hexane column chromatography (toluene: ethyl acetate = 9:1) to afford 75 g of intermediate product Z (yield: 75.4 molpercent) as a white solid.

Reference： [1]Patent: EP2719683,2014,A1 .Location in patent: Paragraph 0158-0161
[2]Patent: EP2727904,2014,A1 .Location in patent: Paragraph 0165; 0167; 0168; 0169; 0170
[3]Patent: US9512251,2016,B2 .Location in patent: Page/Page column 35-36
[4]Patent: US2017/8833,2017,A1 .Location in patent: Paragraph 0199-0202
[5]Patent: TW2018/41897,2018,A .Location in patent: Paragraph 0388-0391

46
[ 1194-98-5 ]
[ 83883-26-5 ]
[ 1416248-89-9 ]

Reference： [1]Patent: EP2727904,2014,A1

47
[ 1194-98-5 ]
[ 2760-98-7 ]
[ 1613485-18-9 ]

Reference： [1]Organic and Biomolecular Chemistry,2014,vol. 12,p. 4445 - 4453

48
[ 1194-98-5 ]
[ 2243-56-3 ]
C₁₇H₁₄N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71.7%	With 10-camphorsufonic acid; In methanol; at 25℃; for 2h;Inert atmosphere;	A four-necked reactor equipped with a thermometer was charged with 5.4 g (39.1 mmol) of 2,5-dihydroxybenzaldehyde, 7.6 g (39.1 mmol) of <strong>[2243-56-3]1-naphthylhydrazine hydrochloride</strong>, and 100 ml of methanol under a nitrogen stream to prepare a homogenous solution. After the addition of 182 mg (0.78 mmol) of (±)-10-camphorsulfonic acid to the solution, the mixture was stirred at 25C for 2 hours. After completion of the reaction, a solid precipitate was filtered off. The solid collected by filtration was washed with methanol, and dried using a vacuum dryer to obtain 7.8 g of a compound (I-3) as an orange solid (yield: 71.7%). [0096] The structure of the target product was identified by 1H-NMR. [0097] The 1H-NMR spectrum data are shown below. [0098] 1H-NMR (500 MHz, DMSO-d6, TMS, delta ppm): 10.54 (s, 1H), 9.82 (s, 1H), 8.83 (s, 1H), 8.47 (s, 1H), 8.50-8.37 (brs, 1H), 8.31 (d, 1H, J=8.0 Hz), 7.87 (d, 1H, J=8.5 Hz), 7.50-7.41 (m, 2H), 7.13 (d, 1H, J=8.5 Hz), 6.98 (d, 1H, J=2.5 Hz), 6.84 (d, 1H, J=8.0 Hz), 6.70 (d, 1H, J=8.5 Hz), 6.61 (dd, 1H, J=3.0 Hz, 8.5 Hz)

Reference： [1]Patent: EP2762465,2014,A1 .Location in patent: Paragraph 0094-0098

49
[ 1194-98-5 ]
[ 2243-56-3 ]
C₄₉H₅₀N₂O₁₀ [ No CAS ]

Reference： [1]Patent: EP2762465,2014,A1

50
[ 1194-98-5 ]
[ 304-20-1 ]
C₄₇H₄₈N₄O₁₀ [ No CAS ]

Reference： [1]Patent: EP2762465,2014,A1

51
[ 15062-88-1 ]
[ 1194-98-5 ]
C₁₄H₁₁N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
95.9%	In ethanol at 25℃; for 4h; Inert atmosphere;	2a.2 Step 2: Synthesis of compound (1-2) A four-necked reactor equipped with a thermometer was charged with 5.4 g (39.1 mmol) of 2,5-dihydroxybenzaldehyde, 5.83 g (39.1 mmol) of the raw material A, and 150 ml of ethanol under a nitrogen stream. The mixture was stirred at 25°C for 4 hours. After completion of the reaction, a solid precipitate was filtered off. The solid collected by filtration was washed with ethanol, and dried using a vacuum dryer to obtain 10.1 g of a compound (I-2) as a white solid (yield: 95.9%). [0090] The structure of the target product was identified by 1H-NMR. [0091] The 1H-NMR spectrum data are shown below. [0092] 1H-NMR (500 MHz, DMSO-d6, TMS, δ ppm): 12.1 (s, 1H), 9.81 (brs, 1H), 8.98 (s, 1H), 8.39 (s, 1H), 7.52 (d, 1H, J=8.0 Hz), 7.40 (d, 1H, J=7.5 Hz), 7.22 (dd, 1H, J=7.5 Hz, 7.5 Hz), 7.13-7.10 (m, 2H), 6.76 (d, 1H, J=8.5 Hz), 6.71 (dd, 1H, J=2.5 Hz, 8.5 Hz)

Reference： [1]Current Patent Assignee: ZEON CORPORATION - EP2762465, 2014, A1 Location in patent: Paragraph 0089-0092

52
[ 1194-98-5 ]
[ 100-63-0 ]
[ 109-77-3 ]
C₁₆H₁₂N₄O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
90%	With CuO/ZrO₂ In water at 40℃; for 1.5h;	2.1. General procedure for the synthesis of pyrazoles General procedure: To equimolar ratios of phenyl hydrazine (1mmol),malononitrile (1mmol) and substituted aldehyde (1 mmol) were dissolved in water(10 mL) at room temperature (R.T), CuO/ZrO2 (20 mg) was added ascatalyst. Reaction mixture was continuously stirred for 1.5 h at 40 °C(Scheme 1) using a magnetic stirrer. The completion of the reactionwas monitored by TLC. The reaction mixture was then filtered, and filtratewas subsequently evaporated under reduced pressure to obtainthe crude product. Further, the crude product was purified with 7:3EtOAc:hexane solvent mixture to afford pure product (4a-l). The recoveredcatalyst was subjected for washing with ethanol, dried and reusedfor up to five cycles.
88%	With zirconia nanopartices incorporated in multi-walled carbon nanotube nanocomposite In water at 20℃; for 2h; Green chemistry;

Reference： [1]Maddila, Suresh; Rana, Surjyakanta; Pagadala, Ramakanth; Kankala, Shravankumar; Maddila, Suryanarayana; Jonnalagadda, Sreekanth B. [Catalysis Communications, 2015, vol. 61, p. 26 - 30]
[2]Halder, Bipasa; Banerjee, Flora; Nag, Ahindra [Applied Organometallic Chemistry, 2020, vol. 34, # 11]

53
[ 1194-98-5 ]
methyl 6-chloro-3-(1-methylhydrazino)-1,1-dioxo-1,4,2-benzodithiazine-7-carboxylate [ No CAS ]
methyl 6-chloro-3-[2-(2,5-dihydroxybenzylidene)-1-methylhydrazino]-1,1-dioxo-1,4,2-benzodithiazine-7-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With acetic acid In methanol at 20℃; for 32h; Reflux;	3.2.3. Procedure for the Preparation of Methyl 6-Chloro-3-[2-(2,4-dihydroxybenzylidene)-1-methylhydrazino]-1,1-dioxo-1,4,2-benzodithiazine-7-carboxylates 15, 16 General procedure: A mixture of methyl 6-chloro-3-(1-methylhydrazino)-1,1-dioxo-1,4,2-benzodithiazine-7-carboxylate 3(1.01 g, 3 mmol), and the corresponding 2,4- or 2,5-dihydroxbenzaldehyde (0.55 g, 4 mmol) glacial acetic acid (0.4 mL, catalytic amount) and methanol (30 mL) was stirred at room temperature for 4 h, followed at reflux for 28 h. After cooling to room temperature and standing overnight, the precipitate was filtered off, washed with methanol (4 × 3 mL), and dried. In this manner the following benzodithiazines were obtained.

Reference： [1]Sławiński, Jarosław; Zołnowska, Beata; Brzozowski, Zdzisław; Kawiak, Anna; Belka, Mariusz; Baczek, Tomasz [Molecules, 2015, vol. 20, # 4, p. 5754 - 5770]

54
[ 1194-98-5 ]
N-methyl-N-(6-chloro-7-methyl-1,1-dioxo-1,4,2-benzodithiazin-3-yl)hydrazine [ No CAS ]
6-chloro-7-methyl-3[2-(2,5-dihydroxybenzylidene)-1-methylhydrazino]-1,1-dioxo-1,4,2-benzodithiazine [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	With acetic acid In ethanol at 20℃; for 28h; Reflux;	3.2.2. General Procedure for the Preparation of 6-Chloro-7-methyl-3-(2-arylmethylene-1-methylhydrazino)-1,1-dioxo-1,4,2-benzodithiazines 5-14 General procedure: A mixture of the benzodithiazinyl hydrazine 2 (1.17 g, 4 mmol), the appropriate aryl carbaldehyde (5 mmol) and glacial acetic acid (0.5 mL, catalytic amount) in ethanol (25 mL) was stirred at room temperature for 3 h, followed at reflux for 25 h. After cooling to room temperature and standing overnight, the precipitate was filtered off, washed with ethanol (4 × 2 mL) and dried. In this manner thefollowing benzodithiazines were obtained.

Reference： [1]Sławiński, Jarosław; Zołnowska, Beata; Brzozowski, Zdzisław; Kawiak, Anna; Belka, Mariusz; Baczek, Tomasz [Molecules, 2015, vol. 20, # 4, p. 5754 - 5770]

55
[ 1194-98-5 ]
[ 5233-04-5 ]
2-(4,6-dichloro-1H-benzo[d]imidazol-2-yl)benzene-1,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	With sodium metabisulfite; In N,N-dimethyl-formamide; for 6h;Reflux;	General procedure: 4.2.7 2-(4,6-dichloro-1H-benzo[d]imidazol-2-yl)benzene-1,4-diol (7) Yield: 85%, 1H NMR (500 MHz, DMSO-d6): delta 13.23(1H), 11.49 (1H), 9.16 (1H), 7.65 (s, 1H), 7.55 (s, 1H), 7.44 (d, J = 1.5 Hz, 1H), 6.91 (d, J = 9.0 Hz, 1H), 6.88 (dd, J = 6.5 Hz, 9.0 Hz, 1H); 13C NMR (75 MHz, DMSO-d6): delta 152.9 (C, C-2), 150.2 (C, C-14), 146.6 (C, C-11), 141.6 (C, C-4), 136.5 (C, C-5), 130.5 (C, C-8), 123.8 (CH, C-7), 122.0 (C, C-6), 119.8 (C, C-10), 117.9 (CH, C-12), 117.2 (CH, C-13), 114.4 (CH, C-15), 113.8 (CH, C-9); Anal. Calcd for C13H8Cl2N2O2 C = 52.91, H = 2.73, N = 9.49. Found: C = 52.89, H = 2.72, N = 9.46; EI MS m/z (% rel. abund.): 297 (M + 2, 23), 295 (M+, 73).

Reference： [1]Bioorganic Chemistry,2015,vol. 61,p. 36 - 44

56
[ 1194-98-5 ]
[ 29620-62-0 ]
N'-[(1E)-(2,5-dihydroxyphenyl)methylidene]quinoline-4-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	With acetic acid In water	8 4.1.1.3. Synthetic procedure for hydrazones preparation General procedure: A quinoline-2-carbohydrazide 4 (100 mg, 0.53 mmol) solution in water (2 mL) was sonicated for 2 min and then aldehyde 5 (0.53 mmol) and acetic acid (0.1 mL) were added dropwise to the reaction mixture. Upon completion of the reaction (20-30 min), the product was filtered, sequentially washed with water (20 mL) and ethyl ether (5 mL), dried in vacuo and recrystallized from ethanol to obtain the corresponding hydrazones in yields ranging from 40% to 85%. 4.1.1.3.8 N'-[(1E)-(2,5-dihydroxyphenyl)methylidene]quinoline-4-carbohydrazide (7c) Yield 62% (0.329 mmol, 101.0 mg); light brown solid, M.p. 270-276 °C; IR (cm-1): νmax 3442 (Ar-OH), 3339 (N-H), 1661 (C=O), 1585 (C=N), 1466 (C=CAr), 1226 ((C=O)-N), 765 (C-HAr). 1H NMR (DMSO-d6): δ 6.77 (H14, H15, sapparent), 7.05 (H17, s), 7.72 (H3, d, J = 4.4 Hz), 7.78-7.89 (H7, H8, m), 8.12 (H6, d, J = 8.5 Hz), 8.19 (H9, d, J = 8.3 Hz), 8.27 (OH), 8.49 (H11, s), 9.03 (H2, d, J = 4.4 Hz), 10.22 (OH), 12.30 (NH). 13C NMR (CDCl3): δ 117.64 (C12), 119.43 (C14, C17), 119.90 (C15), 120.14 (C3), 124.60 (C5), 125.71 (C7), 128.22 (C9), 129.93 (C6), 130.60 (C8), 140.36 (C4), 148.33 (C11), 148.65 (C10), 150.36 (C16), 150.73 (C2), 163.10 (C13), 168.83 (C=O). EIMS: m/z 308.1034 [M+H]+, Calcd for C17H13N3O3: 308.1035.

Reference： [1]Coa, Juan Carlos; Castrillón, Wilson; Cardona, Wilson; Carda, Miguel; Ospina, Victoria; Muñoz, July Andrea; Vélez, Iván D.; Robledo, Sara M. [European Journal of Medicinal Chemistry, 2015, vol. 101, p. 746 - 753]

57
[ 1194-98-5 ]
[ 5055-39-0 ]
(E)-N'-(2,5-dihydroxybenzylidene)-1H-indole-2-carbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	In ethanol for 18h; Reflux;	4.2.1. General procedure for the synthesis of hydrazones (4-17) General procedure: A mixture of hydrazide 3 (1 mmol) and the appropriate aldehyde(1 mmol) in EtOH (10 mL) was refluxed for 18 h. After cooling theformed precipitate was filtered off and purified by crystallization fromthe adequate solvent to give the hydrazone derivatives.
78%	With acetic acid In methanol for 3h; Reflux;	5.2.3.7 (E)-N'-(2,4,6-trihydroxybenzylidene)-1H-indole-2-carbohydrazide (2) General procedure: 1H-Indole-2-carbohydrazones were synthesized by refluxing inmethanol a mixture of 1 mmol each 1H-indole-2-carbohydrazidewith different arylaldehydes catalyzed by acetic acid for 3 h. Theprogress of reaction was monitored by TLC. After completion ofreaction, the solvent was evaporated by vacuum to afford crudeproducts which were further recrystallized in methanol and gotpure product in good to excellent yields.5.2.7 (E)-N'-(2,5-dihydroxybenzylidene)-1H-indole-2-carbohydrazide (3) Yield: 78%. m.p. 278-279 °C; Beige powder; UV (MeOH) λmax (nm) 321; IR(KBr): 3507 cm-1 (OH-str), 3346 cm-1 (2° amine N-H Str), 3050 cm-1 (Ar CH str), 1663 cm-1 (C=N), 1617 cm-1 (Ar C=C), 1546 cm-1 (N-H Bend), 1307-1274 cm-1 (C-N str), 1147 cm-1 (C-O str). 1H NMR (500 MHz, DMSO-d6): δ 12.05 (s, 1H, NH), 11.81 (s, 1H, NH), 10.33 (s, 1H, OH), 9.06 (s, 1H, OH), 8.58 (s, 1H, ArCH=N), 7.69 (d, 1H, J = 8.0 Hz, H-4), 7.48 (d, 1H, J = 8.0 Hz, H-7), 7.32 (s, 1H, H-3), 7.25 (t, 1H, J = 7.5 Hz, H-5), 7.10 (t, 1H, J = 7.0 Hz, H-6), 7.03 (s, 1H, H-6'), 6.78-6.72 (m, 2H, H-4',H-3'); 13C NMR (125 MHz, DMSO-d6): δ 157.30, 153.20, 151.40, 146.10, 139.70, 138.40, 131.20, 121.60, 120.30, 120.10, 119.70, 119.60, 119.40, 116.20, 114.80, 111.10; Anal. Calcd. for C16H13N3O3, C = 65.08, H = 4.44, N = 14.23, Found C = 65.06, H = 4.43, N = 14.24; EI MS m/z (% rel. abund.): 295. (M+, 27), 277 (12), 144 (100), 116 (20), 75 (10).

Reference： [1]Demurtas, Monica; Baldisserotto, Anna; Lampronti, Ilaria; Moi, Davide; Balboni, Gianfranco; Pacifico, Salvatore; Vertuani, Silvia; Manfredini, Stefano; Onnis, Valentina [Bioorganic Chemistry, 2019, vol. 85, p. 568 - 576]
[2]Taha, Muhammad; Ismail, Nor Hadiani; Javaid, Kulsoom; Imran, Syahrul; Anouar, El Hassane; Wadood, Abdul; Atia-Tul-Wahab; Ali, Muhammad; Khan, Khalid Mohammed; Saad, Syed Muhammad; Rahim, Fazal; Choudhary, M. Iqbal [Bioorganic Chemistry, 2015, vol. 63, p. 24 - 35]

58
[ 1194-98-5 ]
[ 15317-58-5 ]
N'-(2,5-dihydroxybenzylidene)-1H-indole-3-carbohydrazide [ No CAS ]

Reference： [1]Medicinal Chemistry Research,2016,vol. 25,p. 1 - 18

59
[ 1635-31-0 ]
[ 1194-98-5 ]
[ 762-21-0 ]
diethyl 3-(2,5-dihydroxyphenyl)-5-oxo-3,5-dihydro-4H-chromeno[3,4-b]pyridine-1,2-dicarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
94%	With bismuth(III) chloride In acetonitrile at 20℃; for 4h; Inert atmosphere; diastereoselective reaction;	One-Pot Procedure General procedure: To a clear colourless solution of 3-aminocoumarin (0.1g, 0.62 mmol) in anhydrous CH3CN (5mL) was added 4-Fluoro benzaldehyde (0.065g, 0.62 mmol), followed by theaddition of BiCl3 (0.0097g, 0.03 mmol %) and DHP (0.145g, 1.73 mmol).The reaction mixture was allowed to stir at room temperature for 4 h. Theprogress of the reaction was monitored by TLC. The reaction mixture wasquenched with 3 mL saturated NaHCO3 solution (pH ≈8.0) checked withlitmus paper and diluted with EtOAc (10 mL). The two layers were separated andthe aqueous layer was extracted with EtOAc (2 × 5 mL). The combined organiclayer was washed with brine (2 × 5 mL), dried over anhydrous Na2SO4and the solvent was removed under reduced pressure, which on purification bysilica gel column chromatography (10% EtOAc/Hexane) provided the desired product (0.19 g, 95.2%) as acolourless solid.

Reference： [1]Gurumurthy, Ch; Fatima, Narjis; Reddy, G. Narender; Kumar, C. Ganesh; Sabitha, Gowravaram; Ramakrishna [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 20, p. 5119 - 5125]

60
[ 13754-19-3 ]
[ 1194-98-5 ]
8-(2,5-dihydroxyphenyl)-7H-purine [ No CAS ]

Reference： [1]ChemMedChem,2017,vol. 12,p. 760 - 769

61
[ 1194-98-5 ]
C₂₃H₃₀O₇ [ No CAS ]
C₃₀H₃₄O₉ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
41%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 15 - 25℃; for 2h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap In tetrahydrofuran at 15 - 25℃; for 2h;	2.1 synthesis of intermediate I In a three-neck reactor equipped with a thermometer, in a nitrogen stream, Intermediate B synthesized in Step 1 of Synthesis Example 1 1.50 g (3.58 mmol) was dissolved in 30 ml of THF . To this solution, Methanesulfonyl chloride (431 mg, 3.76 mmol) Was added, and the reaction vessel was immersed in a water bath to set the internal temperature of the reaction solution at 15 ° C. Thereto, triethylamine 399 mg (3.94 mmol) Was added dropwise over 5 minutes, and after completion of the dropwise addition, And the mixture was further stirred at 25 ° C. for 2 hours. The obtained reaction mixture Was added 2,5-dihydroxybenzaldehyde 2.48 g (17.92 mmol), And 40.0 mg of 4- (dimethylamino) pyridine (0.36 mmol) The reactor was again immersed in a water bath to set the internal temperature of the reaction solution at 15 ° C., Triethylamine 440 mg (4.30 mm Ol) was added dropwise over 5 minutes. After completion of the dropwise addition, The whole of the mixture was stirred at 25 ° C. for 2 hours.After completion of the reaction, 300 ml of distilled water And 50 ml of a saturated saline solution were added, and ethyl acetate 10 It was extracted twice with 0 ml. After drying the organic layer with anhydrous sodium sulfate, Sodium sulfate was filtered off. After concentrating the filtrate with a rotary evaporator, 100 ml of toluene was added to the concentrate In addition, the insoluble solid was removed by filtration. After concentrating the filtrate with a rotary evaporator, The concentrate was purified by silica gel column chromatography (toluene: THF = 95: 5) To obtain 0.80 g of Intermediate I as a white solid Obtained (Yield: 41.0%).
41%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 15 - 25℃; for 2h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap In tetrahydrofuran at 15 - 25℃; for 2h; Inert atmosphere;	2.1 (Synthesis Example 2) Synthesis of Compound 2Step 1: Synthesis of Intermediate I Into a three-necked reactor equipped with a thermometer, in a nitrogen stream,1.50 g (3.58 mmol) of Intermediate B synthesized in Step 1 of Synthesis Example 1,Was dissolved in 30 ml of THF.431 mg (3.76 mmol) of methanesulfonyl chloride was added to this solution, and the reactor was immersed in a water bath to set the internal temperature of the reaction solution to 15 ° C.Thereto, 399 mg (3.94 mmol) of triethylamine was added dropwise over 5 minutes, and after completion of the dropwise addition, the mixture was further stirred at 25 ° C. for 2 hours.2.48 g (17.92 mmol) of 2,5-dihydroxybenzaldehyde and 40.0 mg (0.36 mmol) of 4- (dimethylamino) pyridine were added to the obtained reaction mixture, and the reactor was again immersed in a water bath 440 mg (4.30 mmol) of triethylamine was added dropwise over 5 minutes while setting the internal temperature of the reaction solution at 15 ° C. After completion of the dropwise addition, the whole of the mixture was stirred at 25 ° C. for 2 hours.After completion of the reaction, 300 ml of distilled water and 50 ml of saturated brine were added to the reaction solution, and the mixture was extracted twice with 100 ml of ethyl acetate.After drying the organic layer with anhydrous sodium sulfate, sodium sulfate was filtered off.After concentrating the filtrate with a rotary evaporator, 100 ml of toluene was added to the concentrateIn addition, the insoluble solid was removed by filtration. After concentrating the filtrate with a rotary evaporator, the concentrate was purified by silica gel column chromatography (toluene: THF = 95: 5) to obtain 0.80 g of Intermediate I as a white solid (yield: 41. 0%).
41%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 15 - 25℃; for 2h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap In tetrahydrofuran at 15 - 25℃;	2.1 Step 1: Synthesis of Intermediate I In a three-neck reactor equipped with a thermometer,In a nitrogen stream,1.50 g (3.58 mmol) of Intermediate B synthesized in Step 1 of Synthesis Example 1 was dissolved in 30 ml of THF.To this solution,Methane sulfonyl chloride (431 mg, 3.76 mmol) was added, and the reactor was immersed in a water bath to set the internal temperature of the reaction solution to 15 ° C.Thereto, 399 mg (3.94 mmol) of triethylamine was added dropwise over 5 minutes, and after completion of the dropwise addition,And the mixture was further stirred at 25 ° C. for 2 hours.To the resulting reaction mixture,2.48 g (17.92 mmol) of 2,5-dihydroxybenzaldehyde and 40.0 mg (0.36 mmol) of 4- (dimethylamino) pyridine were added and again the reactor was immersed in a water bath to adjust the internal temperature of the reaction solution to 15 ° C. age,440 mg (4.30 mmol) of triethylamine was added dropwise over 5 minutes.After completion of the dropwise addition,The whole of the mixture was stirred at 25 ° C. for 2 hours.After completion of the reaction,To the reaction solution were added 300 ml of distilled water and 50 ml of a saturated saline solution,And extracted twice with 100 ml of ethyl acetate.After drying the organic layer with anhydrous sodium sulfate,Sodium sulfate was filtered off.After concentrating the filtrate with a rotary evaporator,100 ml of toluene was added to the concentrate, and the insoluble solid was removed by filtration.After concentrating the filtrate with a rotary evaporator,The concentrate was purified by silica gel column chromatography (toluene: THF = 95: 5) to obtain 0.80 g of Intermediate I as a white solid (yield: 41.0%).

32%	Stage #1: C₂₃H₃₀O₇ With thionyl chloride; N,N-dimethyl-formamide In toluene at 5℃; for 1h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With triethylamine In tetrahydrofuran at 5℃; for 0.5h; Inert atmosphere;	1.4 Step 4: Synthesis of intermediate N Into a three-neck reactor equipped with a thermometer, 3.90 g (8.85 mmol) of Intermediate A synthesized in Step 1 of Synthesis Example 1, 0.52 g (7.1 mmol) of DMF and 39 g of toluene were introduced in a nitrogen stream added. The solution was cooled to 5 ° C., 1.10 g (9.3 mmol) of thionyl chloride was added dropwise over 10 minutes, and the reaction was carried out at 5 ° C. for 1 hour. After that, the reaction solution was concentrated with a rotary evaporator and then vacuum-dried to obtain a white solid.In a three-neck reactor equipped with a thermometer, 6.10 g (0.0443 mol) of 2,5-dihydroxybenzaldehyde and 0.985 g (9.7 mmol) of triethylamine were placed in a nitrogen stream and dissolved in 35 g of THF . The solution was cooled to 5 ° C., the white solid obtained above was added and reacted for 30 minutes. Thereafter, 200 ml of distilled water and 10 ml of saturated saline were added to the reaction solution, and the mixture was extracted twice with 100 ml of ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. After concentrating with a rotary evaporator, purification by silica gel column chromatography (toluene: THF = 95: 5) gave 1.53 g of Intermediate N (yield: 32 mol%) as a white solid.
32%	Stage #1: C₂₃H₃₀O₇ With thionyl chloride; triethylamine; N,N-dimethyl-formamide In toluene at 5℃; for 1.166h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With triethylamine In tetrahydrofuran at 5℃; for 0.5h; Inert atmosphere;	14.1 Step 1: Synthesis of intermediate K In the three-neck reactor equipped with a thermometer, the intermediate product A synthesized in the first step of Synthesis Example 1 was added: 3.90 g (8.85 mmol), DMF 0.52 g (7.1 mmol), and toluene 39 g. The solution was cooled to 5 ° C, and 1.10 g (9.3 mmol) of sulfinium chloride was added dropwise over 10 minutes, and then allowed to react at 5 ° C for 1 hour. after that,The reaction liquid was concentrated by a rotary evaporator and dried under vacuum, whereby a white solid was obtained. Further, in a three-neck reactor equipped with a thermometer, 6.10 g (0.0443 mol) of 2,5-dihydroxybenzaldehyde, 0.985 g (9.7 mmol) of triethylamine, and 35 g of THF were charged and dissolved under the nitrogen stream. The solution was cooled to 5 ° C, and the white solid obtained above was added and allowed to react for 30 minutes. After that, 200 mL of distilled water and 10 mL of saturated brine were added to the reaction liquid, and the mixture was extracted twice with 100 mL of ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered. After concentration by a rotary evaporator, the obtained residue was refined by silica gel column chromatography (toluene: THF = 95: 5), and 1.53 g of an intermediate product K as a white solid was obtained (yield: 32 mole %).
1.53 g	Stage #1: C₂₃H₃₀O₇ With thionyl chloride In N,N-dimethyl-formamide; toluene at 5℃; for 1h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With triethylamine In tetrahydrofuran; N,N-dimethyl-formamide; toluene at 5℃; for 0.5h; Inert atmosphere;	1.4 Step 4: Synthesis of intermediate N Into a three-neck reactor equipped with a thermometer, 3.90 g (8.85 mmol) of Intermediate A synthesized in Step 1 of Synthesis Example 1, 0.52 g (7.1 mmol) of DMF and 39 g of toluene were introduced in a nitrogen stream added. The solution was cooled to 5 ° C., 1.10 g (9.3 mmol) of thionyl chloride was added dropwise over 10 minutes, and the reaction was carried out at 5 ° C. for 1 hour. After that, the reaction solution was concentrated with a rotary evaporator and then vacuum-dried to obtain a white solid.In a three-neck reactor equipped with a thermometer, 6.10 g (0.0443 mol) of 2,5-dihydroxybenzaldehyde and 0.985 g (9.7 mmol) of triethylamine were placed in a nitrogen stream and dissolved in 35 g of THF . The solution was cooled to 5 ° C., the white solid obtained above was added and reacted for 30 minutes. Thereafter, 200 ml of distilled water and 10 ml of saturated saline were added to the reaction solution, and the mixture was extracted twice with 100 ml of ethyl acetate. The obtained organic layer was dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. After concentrating with a rotary evaporator, purification by silica gel column chromatography (toluene: THF = 95: 5) gave 1.53 g of Intermediate N (yield: 32 mol%) as a white solid.

Reference： [1]Current Patent Assignee: ZEON CORPORATION - JP6090514, 2017, B1 Location in patent: Paragraph 0214-0215
[2]Current Patent Assignee: ZEON CORPORATION - JP6191793, 2017, B1 Location in patent: Paragraph 0213-0215
[3]Current Patent Assignee: ZEON CORPORATION - JP2017/206554, 2017, A Location in patent: Paragraph 0213-0215
[4]Current Patent Assignee: ZEON CORPORATION - JP2017/206490, 2017, A Location in patent: Paragraph 0351; 0360; 0361
[5]Current Patent Assignee: ZEON CORPORATION - TW2018/35058, 2018, A Location in patent: Paragraph 0545-0552
[6]Current Patent Assignee: ZEON CORPORATION - JP2017/206504, 2017, A Location in patent: Paragraph 03360-0362

62
[ 1194-98-5 ]
[ 1115-70-4 ]
C₁₁H₁₅N₅O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol;Alkaline conditions; Reflux;	General procedure: The Schiff-bases have been prepared by addition of methanolic MF solution to a methanolic solution of the aldehyde in 1:1 ratio in basic medium [24]. The mixture was refluxed with continuous stirring over water bath for two hours. The solution turned to yellow color indicating the formation of the Schiff-base.
	In methanol; for 2h;Reflux; Alkaline conditions;	General procedure: The Schiff-bases have been prepared by addition of methanolicMF solution to a methanolic solution of the aldehyde in1:1 mol ratio in basic medium [11]. The mixture was refluxedwith continuous stirring over water bath for 2 h. The solutionturned to yellow color indicating the formation of the Schiffbase.Only, HL1 Schiff-base was isolated in the solid state,dried under vacuum and recrystallized from methanol (m.p.195 C). We followed the same method in preparation of theother Schiff-bases with different aldehydes but trials to obtainthe solid compounds were unsuccessful. Accordingly, theSchiff-bases were obtained dissolved in methanol solutionand used further for template synthesis of the complexes.

Reference： [1]Journal of Thermal Analysis and Calorimetry,2017,vol. 128,p. 957 - 969
[2]Journal of Fluorescence,2019,vol. 29,p. 319 - 333

63
[ 1194-98-5 ]
[ 6373-46-2 ]
(E)-2-(((4-(benzyloxy)phenyl)imino)methyl)benzene-1,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	In ethanol at 20℃;	4.4 General procedures for the preparation of compound 1-18 General procedure: The respective salicylaldehyde derivatives (5.0 mmol) wereadded to a solution of compound 3a (5.0 mmol) in ethanol(10 mL). The mixture was stirred under room temperature for 2-5 h then followed by filtration and recrystallization in EtOAc orMeOH to obtain the pure compounds.

Reference： [1]Yang, Hua-Li; Cai, Pei; Liu, Qiao-Hong; Yang, Xue-Lian; Fang, Si-Qiang; Tang, Yan-Wei; Wang, Cheng; Wang, Xiao-Bing; Kong, Ling-Yi [Bioorganic and Medicinal Chemistry, 2017, vol. 25, # 21, p. 5917 - 5928]

64
[ 2785-98-0 ]
[ 1194-98-5 ]

Yield	Reaction Conditions	Operation in experiment
18.7 g	With boron tribromide; In dichloromethane; for 2h;Inert atmosphere; Cooling with ice;	In a nitrogen atmosphere, 20.0 g of the compound represented by Formula (I-106-1), 8.8 g of tert-butyl alcohol, 1.3 g of N,N-dimethylaminopyridine, and 100 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 16.3 g of diisopropylcarbodiimide was added dropwise to the mixture. The mixture was then stirred at room temperature for eight hours. After the precipitate had been filtered away, the filtrate was washed with 5%-hydrochloric acid and subsequently with a saline solution. Then, purification was performed by column chromatography (silica gel, dichloromethane). Hereby, 20.8 g of the compound represented by Formula (I-106-2) was prepared. (0142) To a reaction container, 20.8 g of the compound represented by Formula (I-106-2), 200 mL of methanol, and 30 mL of a 25%-aqueous sodium hydroxide solution were added. The resulting mixture was stirred while being heated at 60 C. After the mixture had been cooled, chloroform was added to the mixture. To the mixture, 10%-hydrochloric acid was further added such that the pH of the aqueous layer became 4 to 5. Thus, liquid separation was performed. The organic layer was washed with a saline solution and dried with sodium sulfate. After the insoluble substance had been filtered with celite, the solvent was distilled away and drying was subsequently performed. Hereby, 17.7 g of the compound represented by Formula (I-106-3) was prepared. (0143) In a nitrogen atmosphere, 17.7 g of the compound represented by Formula (I-106-3) and 100 mL of tetrahydrofuran were added to a reaction container. While the resulting mixture was cooled with ice, 103 mL of a 0.9-mol/L borane-tetrahydrofuran complex was added dropwise to the mixture. The mixture was then stirred for one hour. After 5%-hydrochloric acid had been added dropwise to the mixture, extraction with ethyl acetate and washing with a saline solution were performed. Then, drying was performed with sodium sulfate, and the solvent was subsequently distilled away. Hereby, 14.9 g of the compound represented by Formula (I-106-4) was prepared. (0144) In a nitrogen atmosphere, 14.9 g of the compound represented by Formula (I-106-4), 7.2 g of pyridine, and 150 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 8.8 g of methanesulfonyl chloride was added dropwise to the mixture. The mixture was then stirred at room temperature for three hours and poured into water. Subsequently, washing with 5%-hydrochloric acid and then with a saline solution was performed. Then, purification was performed by column chromatography (silica gel, hexane/ethyl acetate) and recrystallization (acetone/hexane). Hereby, 16.3 g of the compound represented by Formula (I-106-5) was prepared. (0145) In a nitrogen atmosphere, 25.0 g of the compound represented by Formula (I-106-6) and 200 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 113.1 g of boron tribromide was added dropwise to the mixture. Then, the mixture was stirred for two hours. After the mixture had been poured into ice water, extraction with ethyl acetate and washing with water and subsequently with a saline solution were performed. Then, purification was performed by column chromatography (alumina, ethyl acetate). Hereby, 18.7 g of the compound represented by Formula (I-106-7) was prepared. (0146) In a nitrogen atmosphere, 2.5 g of the compound represented by Formula (I-106-7), 10.6 g of the compound represented by Formula (I-106-5), 7.5 g of potassium carbonate, and 70 mL of N,N-dimethylformamide were added to a reaction container. The resulting mixture was stirred for 3 days while being heated at 90 C. After the mixture had been poured into water, extraction with toluene and washing with a saline solution were performed. Subsequently, purification was performed by column chromatography (silica gel, toluene) and recrystallization (acetone/methanol). Hereby, 7.7 g of the compound represented by Formula (I-106-8) was prepared. (0147) To a reaction container, 7.7 g of the compound represented by Formula (I-106-8), 150 mL of dichloromethane, and 100 mL of formic acid were added. The resulting mixture was heated to reflux for eight hours. After the solvent had been distilled away, the resulting solid was washed with water and then dried. Hereby, 5.5 g of the compound represented by Formula (I-106-9) was prepared. (0148) In a nitrogen atmosphere, 5.5 g of the compound represented by Formula (I-106-9), 6.9 g of the compound represented by Formula (I-106-10), 0.8 g of N,N-dimethylaminopyridine, and 200 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 4.1 g of diisopropylcarbodiimide was added dropwise to the mixture, which was then stirred at room temperature for 10 hours. After the precipitate had been filtered away, the filtrate was washed with 1%-hydrochloric acid, with water, an...

Reference： [1]Patent: US2018/2276,2018,A1 .Location in patent: Paragraph 0140-0154

65
[ 1194-98-5 ]
C₂₃H₃₀O₇ [ No CAS ]
C₅₃H₆₂O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
91%	With dmap; sulfuric acid; diisopropyl-carbodiimide In dichloromethane at 20℃; for 5h; Inert atmosphere; Cooling with ice;	3 (Example 3) Production of a compound represented by formula (I-3) Under a nitrogen atmosphere, 8.0 g of the compound represented by the formula (I-3-1), 1.3 g of the compound represented by the formula (I-3-2), and 0.58 g of 4-dimethylaminopyridine were added to the reaction vessel. 80 mL of methyl chloride and 0.47 g of concentrated sulfuric acid.While ice-cooling, 2.7 g of diisopropylcarbodiimide was added dropwise, and the mixture was stirred at room temperature for 5 hours.After the precipitate was removed by filtration, the solvent was distilled off and washed with methanol.Purification by column chromatography (alumina, dichloromethane) and reprecipitation (dichloromethane/methanol) gave 8.2 g of the compound of formula (I-3).The yield of the compound represented by the formula (I-3) was 91%.After the reaction, 1.6% of N-mercaptourea represented by the formula (I-3-A) was produced.N-mercapto urea represented by the formula (I-3-A) was not detected in the compound represented by the formula (I-3) after purification.
7.1 g	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 10h; Inert atmosphere; Cooling with ice;	9 Production of the Compound Represented by Formula (I-109) To a reaction container equipped with a Dean and Stark device, 30.0 g of the compound represented by Formula (I-109-1), 19.0 g of acrylic acid, 2.1 g of p-toluenesulfonic acid monohydrate, 300 mL of cyclohexane, and 150 mL of diisopropyl ether were added. The resulting mixture was heated to reflux for 12 hours while water was removed from the mixture. Subsequently, dilution with dichloromethane and washing with a 5%-sodium hydrogencarbonate aqueous solution and then with a saline solution were performed. Then, purification was performed by column chromatography (silica gel, dichloromethane). Hereby, 33.5 g of the compound represented by Formula (I-109-2) was prepared. (0173) To a reaction container, 10.0 g of the compound represented by Formula (I-109-2), 28.9 g of hydroquinone, 21.7 g of potassium carbonate, and 150 mL of acetone were added. The resulting mixture was heated to reflux for eight hours. After the mixture had been poured into 5%-hydrochloric acid, extraction with dichloromethane and cleaning with a saline solution were performed. Then, purification was performed by column chromatography (alumina, dichloromethane) and recrystallization (dichloromethane/hexane). Hereby, 9.7 g of the compound represented by Formula (I-109-3) was prepared. (0174) In a nitrogen atmosphere, 9.7 g of the compound represented by Formula (I-109-3), 7.9 g of the compound represented by Formula (I-109-4), 0.4 g of N,N-dimethylaminopyridine, and 100 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 5.6 g of diisopropylcarbodiimide was added dropwise to the mixture, which was then stirred at room temperature for 6 hours. After the precipitate had been filtered away, the filtrate was washed with 1%-hydrochloric acid, with water, and then with a saline solution. Subsequently, purification was performed by column chromatography (alumina, dichloromethane) and recrystallization (dichloromethane/methanol). Hereby, 11.9 g of the compound represented by Formula (I-109-5) was prepared. (0175) To a reaction container, 11.9 g of the compound represented by Formula (I-109-5) and 80 mL of dichloromethane were added. To the resulting mixture, 20 mL of trifluoroacetic acid was added dropwise. The mixture was then stirred for eight hours. After the solvent had been distilled away, diisopropyl ether was added to the mixture to precipitate a solid, which was then filtered. The solid was washed with diisopropyl ether and subsequently dried. Hereby, 10.7 g of the compound represented by Formula (I-109-6) was prepared. (0176) In a nitrogen atmosphere, 9.1 g of the compound represented by Formula (I-109-6), 1.5 g of the compound represented by Formula (I-109-7), 0.1 g of N,N-dimethylaminopyridine, and 150 mL of dichloromethane were added to a reaction container. While the resulting mixture was cooled with ice, 3.4 g of diisopropylcarbodiimide was added dropwise to the mixture, which was then stirred at room temperature for 10 hours. After the precipitate had been filtered away, the filtrate was washed with 1%-hydrochloric acid, with water, and then with a saline solution. After recrystallization (dichloromethane/methanol) had been performed, purification was performed by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane/methanol). Hereby, 7.1 g of the compound represented by Formula (I-109-8) was prepared. (0177) To a reaction container, 10.0 g of the compound represented by Formula (I-109-9), 13.8 g of the compound represented by Formula (I-109-2), 12.5 g of potassium carbonate, and 100 mL of N,N-dimethylformamide were added. The resulting mixture was stirred for 8 hours while being heated at 70° C. After dilution had been performed with dichloromethane, washing with water and then with a saline solution was performed. Subsequently, purification was performed by column chromatography (alumina, dichloromethane). Hereby, 11.6 g of the compound represented by Formula (I-109-10) was prepared. (0178) To a reaction container, 2.0 g of the compound represented by Formula (I-109-10), 5.9 g of the compound represented by Formula (I-109-8), 0.7 g of (±)-10-camphorsulfonic acid, 24 mL of tetrahydrofuran, and 24 mL of ethanol were added. The resulting mixture was stirred for 8 hours while being heated at 50° C. After the solvent had been distilled away, purification was performed by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane/methanol). Hereby, 5.4 g of the compound represented by Formula (I-109) was prepared. (0179) 1H NMR (CDCl3) δ 1.24 (m, 4H), 1.48-1.93 (m, 28H), 2.08 (t, 4H), 2.23 (m, 4H), 2.54 (m, 4H), 3.94 (t, 4H), 4.17 (t, 4H), 4.53 (t, 2H), 4.65 (t, 2H), 5.82 (dd, 3H), 6.12 (dd, 3H), 6.40 (dd, 3H), 6.88 (m, 6H), 6.97 (dd, 4H), 7.16 (t, 1H), 7.34 (t, 1H), 7.54 (d, 1H), 7.66 (d, 1H), 7.70 (d, 1H), 8.36 (s, 1H) ppm. (0180) LCMS: 1240 [M+1]
7.1 g	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 10h; Inert atmosphere; Cooling with ice;	5 In a nitrogen atmosphere, 9.1 g of the compound represented by the formula (I-5-6), 1.5 g of the compound represented by the formula (I-5-7), 0.1 g of N,N-dimethylaminopyridine and 150 mL of dichloromethane were put into a reactor. With cooling with ice, 3.4 g of diisopropylcarbodiimide was dropwise added and stirred at room temperature for 10 hours. The precipitate was removed through filtration, and the filtrate was washed sequentially with 1% hydrochloric acid, water and salt water. After recrystallization (dichloromethane/methanol), purification through column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane/methanol) gave 7.1 g of the compound represented by the formula (I-5-8).

3.3 g	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 8h; Inert atmosphere; Cooling with ice;	14 Under a nitrogen atmosphere, 4.0 g of the compound represented by Formula (I-12-6), 0.7 g of the compound represented by Formula (I-12-7), 0.1 g of N,N-dimethylaminopyridine, and 40 mL of dichloromethane were added to a reaction container. 1.5 g of diisopropylcarbodiimide was added dropwise thereto while cooling with ice, and the mixture was stirred at room temperature for 8 hours. After filtration of the solid, the filtrate was washed with a 5% hydrochloric acid and a saline solution. Purification was performed by column chromatography (silica gel) and recrystallization (dichloromethane/methanol) to obtain 3.3 g of a compound represented by Formula (I-12-8).
3.3 g	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 20℃; for 8h; Inert atmosphere; Cooling with ice;	15 4.0 g of the compound represented by the formula (I-10-6) and 0.7 g of the compound represented by the formula (I-10-7) under a nitrogen atmosphere.0.1 g of N,N-dimethylaminopyridine and 40 mL of dichloromethane were placed in a reaction vessel.While ice-cooling, 1.5 g of diisopropylcarbodiimide was added dropwise, and the mixture was stirred at room temperature for 8 hours.After filtering the solid matter, the filtrate was washed with 5% hydrochloric acid and brine.Purification by column chromatography (hydrazine gel, dichloromethane) and recrystallization (dichloromethane/methanol) afforded 3.3 g of the compound of formula (I-10-8).
3.3 g	With dmap; diisopropyl-carbodiimide In dichloromethane at 20℃; for 8h; Inert atmosphere; Cooling with ice;	15 In a nitrogen atmosphere, 4.0 g of a compound represented by formula (I-10-6), 0.7 g of a compound represented by formula (I-10-7), 0.1 g of N,N-dimethylaminopyridine, and 40 mL of dichloromethane were added into a reactor. While the mixture was being cooled over ice, 1.5 g of diisopropylcarbodiimide was added dropwise, followed by stirring at room temperature for 8 hours. After the solid matter was filtered, and the filtrate was washed with a 5% hydrochloric acid and brine. Purification by column chromatography (silica gel, dichloromethane) and recrystallization (dichloromethane/methanol) was performed to obtain 3.3 g of a compound represented by formula (I-10-8).

Reference： [1]Current Patent Assignee: DIC CORP. - TW2019/12621, 2019, A Location in patent: Paragraph 0184-0187
[2]Current Patent Assignee: DIC CORP. - US2018/2276, 2018, A1 Location in patent: Paragraph 0171-0180
[3]Current Patent Assignee: DIC CORP. - US2018/312481, 2018, A1 Location in patent: Paragraph 0135; 0140
[4]Current Patent Assignee: DIC CORP. - US2018/354922, 2018, A1 Location in patent: Paragraph 0158; 0163
[5]Current Patent Assignee: DIC CORP. - TW2019/14995, 2019, A Location in patent: Paragraph 0166; 0171
[6]Current Patent Assignee: DIC CORP. - US2020/165215, 2020, A1 Location in patent: Paragraph 0146; 0151

66
[ 1194-98-5 ]
C₂₃H₃₀O₇ [ No CAS ]
C₅₃H₆₂O₁₅ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 20 - 30℃; for 2h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap; triethylamine In tetrahydrofuran at 15 - 30℃; for 2h;	1.2 Step 2: Synthesis of Intermediate B Into a three-neck reactor equipped with a thermometer, 4.00 g (9.56 mmol) of Intermediate A synthesized in Step 1 and 60 ml of THF synthesized in Step 1 above were placed in a nitrogen stream to obtain a uniform solution. Thereto, 1.12 g (9.78 mmol) of methanesulfonyl chloride was added, and the reactor was immersed in a water bath to set the internal temperature of the reaction solution to 20 ° C. Subsequently, 1.01 g (9.99 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the dropwise addition, the whole of the mixture was stirred at 25 ° C. for 2 hours. To the resulting reaction solution, 0.11 g (0.87 mmol) of 4- (dimethylamino) pyridine and 0.60 g (4.35 mmol) of 2,5-dihydroxybenzaldehyde were added, and the reactor was again immersed in a water bath The internal temperature of the reaction solution was 15 ° C. Thereto, 1.10 g (10.87 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the dropwise addition, the whole volume was further stirred at 25 ° C. for 2 hours. After completion of the reaction, 400 ml of distilled water and 50 ml of a saturated saline solution were added to the reaction solution, and the mixture was extracted twice with 750 ml of ethyl acetate. The organic layer was collected, dried over anhydrous sodium sulfate and filtered over sodium sulfate. After evaporating off the solvents from the filtrate on a rotary evaporator, dissolve the resultant residue in 100 ml of THF. The solution was added to methanol 500ml to precipitate crystals, and the precipitated crystals were collected by filtration. After washing the obtained crystals with methanol and dried in vacuo to yield intermediate B was obtained 2.51g as a white solid (yield: 62 mol%).
62%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride In tetrahydrofuran at 20 - 30℃; for 2.166h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap; triethylamine at 15 - 30℃; for 2.083h;	1.2 Step 2: Synthesis of Intermediate B In a three-neck reactor equipped with a thermometer, 4.00 g (9.56 mmol) of the intermediate product A synthesized in the above step 1 and 60 mL of THF were placed in a nitrogen stream to prepare a homogeneous solution.At this time, 1.12 g (9.78 mmol) of methanesulfonium chloride was added.The reactor was immersed in a water bath to set the internal temperature of the reaction liquid to 20 °C.Next,1.01 g (9.99 mmol) of triethylamine was kept while maintaining the internal temperature of the reaction solution at 20 to 30 ° C.It took 10 minutes to drop,After the drop,The whole was further stirred at 25 ° C for 2 hours.In the resulting reaction solution,Addition of 4-(dimethylamino)pyridine 0.11 g (0.87 mmol)And 2,5-dihydroxybenzaldehyde 0.60g (4.35mmol),The reactor was again immersed in a water bath to set the internal temperature of the reaction liquid to 15 °C.At this time, 1.10 g (10.87 mmol) of triethylamine was kept at a temperature of 20 to 30 ° C while the internal temperature of the reaction solution was dropped for 5 minutes.After the drop,The whole was further stirred at 25 ° C for 2 hours.After the reaction,400 mL of distilled water and 50 mL of saturated brine were added to the reaction solution.It was extracted twice with 750 mL of ethyl acetate.Collect organic layers,Drying with anhydrous sodium sulfate,And filtered sodium sulfate.The solvent is evaporated from the filtrate using a rotary evaporator.The resulting residue was dissolved in 100 mL of THF.500 mL of methanol was added to the solution to precipitate crystals.The precipitated crystals were obtained by filtration. After washing the obtained crystals with methanol,Let it dry in vacuum,There was obtained 2.51 g of an intermediate product B as a white solid (yield: 62 mol%).
62%	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 20 - 30℃; for 2.08333h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap; triethylamine In tetrahydrofuran at 15 - 30℃; for 2.08333h; Inert atmosphere;	1.2 Step 2: Synthesis of Intermediate X1 4.00 g (9.56 mmol) of Intermediate P synthesized in Step 1 and 60 ml of THF were charged into a three-necked reactor equipped with a thermometer, under a nitrogen stream to prepare a uniform solution. After 1.12 g (9.78 mmol) of methanesulfonyl chloride was added thereto, the reactor was immersed in a water bath to adjust the temperature of the reaction solution to 20° C. Next, 1.01 g (9.99 mmol) of triethylamine was added dropwise to the reaction solution over 5 minutes while maintaining the temperature of the reaction solution at 20 to 30° C. After the dropwise addition, the solution was stirred at 25° C. for an additional 2 hours. After 0.11 g (0.87 mmol) of 4-(dimethylamino)pyridine, and, 0.60 g (4.35 mmol) of 2,5-dihydroxybenzaldehyde was added to the obtained reaction solution, the reactor was again immersed in a water bath to adjust the temperature of the reaction solution to 15° C. 1.10 g (10.87 mmol) of triethylamine was added dropwise to the reaction solution over 5 minutes while maintaining the temperature of the reaction solution at 20 to 30° C., After the dropwise addition, the solution was stirred at 25° C. for an additional 2 hours. After completion of the reaction, 400 ml of distilled water and 50 ml of saturated saline solution were added to the reaction solution, followed by extraction twice with 750 ml of ethyl acetate. The organic layer was collected, and dried with anhydrous sodium sulfate, and the sodium sulfate was filtered off. After the solvent was evaporated from the filtrate using a rotary evaporator, the obtained residue was dissolved in 100 ml of THF. 500 ml of methanol was added to the solution to precipitate crystals, which were filtered off. The obtained crystals were washed with methanol, and dried under vacuum to obtain 2.51 g of Intermediate X1 as a white solid. The yield was 62 mol %. The structure of Intermediate X1 was identified by 1H-NMR. The 1H-NMR spectral data is presented below. (0457) 1H-NMR (500 MHz, DMSO-d6, TMS, δppm): 10.02 (s, 1H), 7.67 (d, 1H, J=3.0 Hz), 7.55 (dd, 1H, J=3.0 Hz, 8.5 Hz), 7.38 (d, 1H, J=8.5 Hz), 6.99-7.04 (m, 4H), 6.91-6.96 (m, 4H), 6.32 (dd, 2H, J=1.5 Hz, 17.5 Hz), 6.17 (dd, 2H, J=10.0 Hz, 17.5 Hz), 5.93 (dd, 2H, J=1.5 Hz, 10.0 Hz), 4.11 (t, 4H, J=6.5 Hz), 3.95 (t, 4H, J=6.5 Hz), 2.56-2.81 (m, 4H), 2.10-2.26 (m, 8H), 1.50-1.76 (m, 16H), 1.33-1.49 (m, 8H).

2.51 g	Stage #1: C₂₃H₃₀O₇ With methanesulfonyl chloride; triethylamine In tetrahydrofuran at 20 - 30℃; for 2h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With dmap In tetrahydrofuran at 20 - 30℃; for 2h; Inert atmosphere;	1.2 Step 2: Synthesis of Intermediate B Into a three-necked reactor equipped with a thermometer, the intermediate A4 synthesized in the above step 1 in a nitrogen stream. 00 g (9.56 mmol) and THF 60 ml were charged into a homogeneous solution. Thereto, 1.12 g (9.78 mmol) of methanesulfonyl chloride was added and the reactor was immersed in a water bath to set the internal temperature of the reaction solution to 20 ° C. Subsequently, 1.01 g (9.99 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the dropwise addition, the whole of the mixture was stirred at 25 ° C. for 2 hours. 0.11 g (0.87 mmol) of 4- (dimethylamino) pyridine and 0.6 g (4.35 mmol) of 2,5-dihydroxybenzaldehyde were added to the obtained reaction solution, the reactor was again immersed in a water bath The internal temperature of the reaction solution was 15 ° C. Thereto, 1.10 g (10.87 mmol) of triethylamine was added dropwise over 5 minutes while maintaining the internal temperature of the reaction solution at 20 to 30 ° C. After completion of the dropwise addition, the whole volume was further stirred at 25 ° C. for 2 hours. After completion of the reaction, 400 ml of distilled water and 50 ml of saturated saline were added to the reaction solution, and the mixture was extracted twice with 750 ml of ethyl acetate. The organic layer was collected, dried over anhydrous sodium sulfate, and sodium sulfate was filtered off. After removing the solvent from the filtrate by evaporation with a rotary evaporator, the obtained residue was dissolved in 100 ml of THF. 500 ml of methanol was added to the solution to precipitate crystals, and the precipitated crystals were collected by filtration. The obtained crystals were washed with methanol and vacuum dried to obtain 2.51 g of Intermediate B (yield: 62 mol%) as a white solid.
	With dmap; dicyclohexyl-carbodiimide In dichloromethane
6.8 g	With dmap; diisopropyl-carbodiimide In chloroform at 23℃; for 3h; Inert atmosphere;	1.2 Step 2: Synthesis of intermediate product B(an example of a compound represented by formula (V-1) In a three-necked reactor equipped with a thermometer, in a nitrogen stream, 10.00 g (23.90 mmol) of the intermediate A synthesized in step 1 above, 1.32 g (9.56 mmol) of 2,5-dihydroxybenzaldehyde, and 234 mg (1.92 mmol) of 4- (dimethylamino) pyridine were added to 80 mL of chloroform. N,N'-diisopropylcarbodiimide 3.2 g (25.36 mmol) was slowly added dropwise at room temperature. After the completion of the dropwise addition, the mixture was stirred at 23 ° C for 3 hours. After completion of the reaction, the reaction solution was directly purified by silica gel column chromatography (becomes a gradient of only chloroform to chloroform: THF = 9:1 (volume ratio))to obtain 6.80 g of Intermediate B as a white solid, yield 75.7 mol%.
9.77 g	Stage #1: C₂₃H₃₀O₇ With thionyl chloride; N,N-dimethyl-formamide In chloroform at 10 - 25℃; for 1h; Inert atmosphere; Stage #2: 2,5-Dihydroxybenzaldehyde With 2,6-dimethylpyridine In chloroform at 10℃; for 1h; Inert atmosphere;	1 (Example 1) Synthesis of Polymerizable Compound (1-1) (Example of the Polymerizable Compound Represented by Formula (VI)) 10.00 g (23.90 mmol) of the compound M synthesized in the Synthesis Example 11, 100 g of chloroform, and 3.49 g of dimethylformamide (DMF) were added in a three-necked reactor equipped with a thermometer, under a nitrogen stream, and cooled to 10° C. or less. 3.27 g (27.48 mmol) of thionyl chloride was dropped in the solution while controlling the reaction temperature to 10° C. or less. After the dropwise addition, the reaction solution was returned to 25° C. and stirred for 1 hour. After completion of the reaction, the amount of the reaction solution was concentrated using an evaporator until the amount of the reaction solution became a quarter of the initial amount. Then, 25 g of chloroform was added to obtain the chloroform solution. Separately, 1.50 g (10.86 mmol) of 2,5-dihydroxybenzaldehyde represented by the aforementioned formula (A), and 6.98 g (65.17 mmol) of 2,6-lutidine (pKa: 6.65) as a base were dissolved in 50 g of chloroform in a three-necked reactor equipped with a thermometer under a nitrogen stream, and cooled to 10° C. or less. A chloroform solution was gradually dropped in the solution while maintaining the internal temperature of the reaction solution at 10° C. or less. After the dropwise addition, the reaction solution was further reacted for 1 hour while maintaining at 10° C. or less (Step 1). When the obtained reaction solution was analyzed by high performance liquid chromatography (HPLC) and quantified by a calibration curve, it is understood that 9.77 g (10.40 mmol) of the polymerizable compound (polymerizable compound (1): example of the compound represented by formula (III)) represented by the aforementioned formulas (1) was contained. The yield was 95.75 mol %.

Reference： [1]Current Patent Assignee: ZEON CORPORATION - JP2017/206490, 2017, A Location in patent: Paragraph 0294; 0298; 0299; 0373; 0374
[2]Current Patent Assignee: ZEON CORPORATION - TW2018/35058, 2018, A Location in patent: Paragraph 0349; 0355-0358
[3]Current Patent Assignee: ZEON CORPORATION - US2020/31786, 2020, A1 Location in patent: Paragraph 0455-0457
[4]Current Patent Assignee: ZEON CORPORATION - JP2017/206504, 2017, A Location in patent: Paragraph 0298-0300
[5]Current Patent Assignee: CHISSO CORPORATION - JP2016/128403, 2016, A Location in patent: Paragraph 0222; 0223
[6]Current Patent Assignee: ZEON CORPORATION - TW2018/41897, 2018, A Location in patent: Paragraph 0272; 0276-0278
[7]Current Patent Assignee: ZEON CORPORATION - US2020/283399, 2020, A1 Location in patent: Paragraph 0398-0401

67
[ 1194-98-5 ]
[ 54608-52-5 ]
(E)-2-((2-(pyrazin-2-yl)hydrazono)methyl)benzene-1,4-diol [ No CAS ]

Reference： [1]ChemMedChem,2018,vol. 13,p. 1387 - 1394

68
[ 1194-98-5 ]
[ 69408-81-7 ]
2-[2-(dimethylamino)ethyl]-5-[(1Z)-(2,5-dihydroxyphenyl)methylene]amino}-1H-benzo[de]isoquinolin-1,3(2H)-dione hydrochloride [ No CAS ]

Reference： [1]Patent: WO2005/105753,2005,A2

69
[ 1194-98-5 ]
[ 872-35-5 ]
[ 109-77-3 ]
5-(1H-imidazol-2-ylthio)-2,4-diamino-7-hydroxy-5H-chromeno[2,3-b]pyridine-3-carbonitrile [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
83%	With (1E,1'E)-N,N'-(4,10-dimethyl-6H,12H-5,11-methanodibenzo[b,f][1,5]diazocine-2,8-diyl)bis(1-(pyridin-2-yl)methanimine); In ethanol; at 80℃;	5-bromo salicylaldehyde 5 (1 mmol), malononitrile 6 (2.1 mmol), <strong>[872-35-5]2-mercaptoimidazole</strong> 7 (1.1 mmol), compound 4 (20 mol%) and ethanol (5 mL) were sequentially added to a 50 mL round bottom flask, and fully reacted to completion at 80 C (TLC tracking monitoring). After cooling to room temperature, suction filtration, the product was washed with a small amount of water, dissolved in N,N-dimethylformamide, filtered, and distilled. Water, solid precipitated, suction filtration, recrystallization (DMSO) gave compound 8o, yield 83%.The structural formula of compound 8o is:The formula is: C16H11N6O2SChinese name: 5-(1H-imidazol-2-ylthio)-2,4-diamino-7-hydroxy-5H-chromen[2,3-b]pyridin Pyridine-3-carbonitrileEnglish name: 5-(1H-imidazol-2-ylthio)-2,4-diamino-7-hydroxy-5H-chromeno [2,3-b]pyridine-3-carbonitrile

Reference： [1]Patent: CN108610348,2018,A .Location in patent: Paragraph 0139; 0140; 0141; 0142; 0143; 0144

70
[ 3048-01-9 ]
[ 1194-98-5 ]
5-hydroxy-2-(2-(trifluoromethyl)phenyl)-1,3-benzoxazole-4-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	Stage #1: 2,5-Dihydroxybenzaldehyde With manganese(IV) oxide In toluene at 0℃; for 0.25h; Inert atmosphere; Stage #2: o-trifluoromethylbenzylamine In ⁽²⁾H₈-toluene for 10h; Inert atmosphere; Reflux;	Generalexperimental procedure for synthesis of benzo[d]oxazole derivatives (GP) General procedure: A suspension of 2,5-dihydroxybenzaldehye 1 (0.107g,1 mmol, 1equiv.) and MnO2 (0.860g, 10 mmol) in toluene, were cooledin ice bath to 0°C under constant stirring for 15 min and amine (1 mmol, 1equiv.) was added. The mixture was refluxed for 10 h. The mixture was filtered through celite and washed withtoluene. Removal of the solvent under reduced pressure followed by columnchromatography (5% EtOAc/Hexane) yielded pure benzo[d]oxazole derivative.

Reference： [1]Tangellamudi, Neelima D.; Shinde, Suchita B.; Pooladanda, Venkatesh; Godugu, Chandraiah; Balasubramanian, Sridhar [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 23-24, p. 3639 - 3647]

71
[ 1194-98-5 ]
[ 10269-01-9 ]
2-(3-bromophenyl)-5-hydroxy1,3-benzoxazole-4-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
62%	Stage #1: 2,5-Dihydroxybenzaldehyde With manganese(IV) oxide In toluene at 0℃; for 0.25h; Inert atmosphere; Stage #2: 3-bromobenzylamine In ⁽²⁾H₈-toluene for 10h; Inert atmosphere; Reflux;	Generalexperimental procedure for synthesis of benzo[d]oxazole derivatives (GP) General procedure: A suspension of 2,5-dihydroxybenzaldehye 1 (0.107g,1 mmol, 1equiv.) and MnO2 (0.860g, 10 mmol) in toluene, were cooledin ice bath to 0°C under constant stirring for 15 min and amine (1 mmol, 1equiv.) was added. The mixture was refluxed for 10 h. The mixture was filtered through celite and washed withtoluene. Removal of the solvent under reduced pressure followed by columnchromatography (5% EtOAc/Hexane) yielded pure benzo[d]oxazole derivative.

Reference： [1]Tangellamudi, Neelima D.; Shinde, Suchita B.; Pooladanda, Venkatesh; Godugu, Chandraiah; Balasubramanian, Sridhar [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 23-24, p. 3639 - 3647]

72
[ 1194-98-5 ]
[ 2018-90-8 ]
5-hydroxy-2-(naphthalen-2-yl)1,3-benzoxazole-4-carbaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58%	Stage #1: 2,5-Dihydroxybenzaldehyde With manganese(IV) oxide In toluene at 0℃; for 0.25h; Inert atmosphere; Stage #2: naphthalen-2-ylmethylamine In ⁽²⁾H₈-toluene for 10h; Inert atmosphere; Reflux;	Generalexperimental procedure for synthesis of benzo[d]oxazole derivatives (GP) General procedure: A suspension of 2,5-dihydroxybenzaldehye 1 (0.107g,1 mmol, 1equiv.) and MnO2 (0.860g, 10 mmol) in toluene, were cooledin ice bath to 0°C under constant stirring for 15 min and amine (1 mmol, 1equiv.) was added. The mixture was refluxed for 10 h. The mixture was filtered through celite and washed withtoluene. Removal of the solvent under reduced pressure followed by columnchromatography (5% EtOAc/Hexane) yielded pure benzo[d]oxazole derivative.

Reference： [1]Tangellamudi, Neelima D.; Shinde, Suchita B.; Pooladanda, Venkatesh; Godugu, Chandraiah; Balasubramanian, Sridhar [Bioorganic and Medicinal Chemistry Letters, 2018, vol. 28, # 23-24, p. 3639 - 3647]

73
[ 932-52-5 ]
[ 1194-98-5 ]
(E)-5-{(2,5-dihydroxybenzylidene)amino}pyrimidine-2,4(1H,3H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
80%	With acetic acid; In methanol; at 20℃;	General procedure: To a mixture of 5-aminouracil (127 mg, 1 mmol) with an appropriate aldehyde (241 mg, 1.2 mmol) in methanol (15 mL) were added few drops of glacial acetic acid. The reaction mixture was stirred at room temperature until 5-aminouracil was completely consumed (TLC). The precipitate was filtered off, washed with methanol and air dried to give the corresponding product 1-10 as a yellow solid.

Reference： [1]Russian Journal of General Chemistry,2019,vol. 89,p. 122 - 127
Zh. Obshch. Khim.,2019,vol. 89,p. 122 - 127,6

74
[ 1194-98-5 ]
[ 4292-19-7 ]
4-bis(dodecyloxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With potassium carbonate In N,N-dimethyl-formamide for 16h; Inert atmosphere; Reflux;	2.2. General procedure for the alkylation reactions of 2 (Scheme 1) To a solution of the corresponding aldehyde 2 (0.28 mmol) in dryDMF (4 mL) were added the corresponding iodide (3 eq) and potassiumcarbonate (0.11 g, 3 eq). The reaction mixture was stirred under argonatmosphere at reflux over 16 h. The reaction was monitored via TLC.Once the reaction was finished it was quenched with water. The productwas extracted with dichloromethane (3×15 mL) and washedwith water. The organics were dried under vacuum and the crude waspurified by flash chromatography through silica gel using hexane/ethylacetate (9/1) as eluent yielding compounds 3 (Scheme 1).

Reference： [1]Granados, Albert; Vallribera, Adelina [Dyes and Pigments, 2019, vol. 170]

75
[ 1194-98-5 ]
[ 461-17-6 ]
C₁₅H₁₆F₆O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With potassium carbonate; In N,N-dimethyl-formamide; for 16h;Inert atmosphere; Reflux;	To a solution of the corresponding aldehyde 2 (0.28 mmol) in dryDMF (4 mL) were added the corresponding iodide (3 eq) and potassiumcarbonate (0.11 g, 3 eq). The reaction mixture was stirred under argonatmosphere at reflux over 16 h. The reaction was monitored via TLC.Once the reaction was finished it was quenched with water. The productwas extracted with dichloromethane (3×15 mL) and washedwith water. The organics were dried under vacuum and the crude waspurified by flash chromatography through silica gel using hexane/ethylacetate (9/1) as eluent yielding compounds 3 (Scheme 1).

Reference： [1]Dyes and Pigments,2019,vol. 170

76
[ 2518-24-3 ]
[ 1194-98-5 ]
C₁₅H₁₀N₂O₄ [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019

77
[ 2518-24-3 ]
[ 1194-98-5 ]
4-((2,5-dihydroxybenzyl)amino)isoindoline-1,3-dione [ No CAS ]

Reference： [1]Journal of the American Chemical Society,2019

78
[ 19484-57-2 ]
[ 1194-98-5 ]
3,3′-((2′′,5′′-dihydroxyphenyl)methylene)bis(6-chloro-4-hydroxy-2H-chromen-2-one) [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
76%	With tetraethylammonium bromide In water for 2h; Reflux;	4.2. General procedure for the syntheses of bis-coumarin derivatives 1-44 General procedure: 6-Fluoro-4-hydroxy /6-chloro-4-hydroxy /4-hydroxy coumarin(1 mmol), and a variety of aromatic aldehydes (0.5 mmol), as well as 10 mol% of tetraethylammonium bromide (TEAB) were dissolved indistilled water (15 mL) in a 100 mL round-bottommed flask. The reactionmixture was refluxed for 2 h. Periodic TLC was taken to check theprogress of reaction. Resulting precipitates were filtered, and washedwith distilled water. This afforded products 1-44 in high yields.

Reference： [1]Salar, Uzma; Nizamani, Arsalan; Arshad, Fizza; Khan, Khalid Mohammed; Fakhri, Muhammed Imran; Perveen, Shahnaz; Ahmed, Nessar; Choudhary, M. Iqbal [Bioorganic Chemistry, 2019, vol. 91]

79
[ 1194-98-5 ]
[ 29620-62-0 ]
C₁₇H₁₃N₃O₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In water; acetic acid

Reference： [1]Osorio, Edison; Bravo, Karent; Cardona, Wilson; Yepes, Andres; Osorio, Edison H.; Coa, Juan C. [Medicinal Chemistry Research, 2019, vol. 28, # 11, p. 1959 - 1973]

80
[ 1194-98-5 ]
[ 3447-53-8 ]
2-((4-(difluoromethoxy)benzyl)oxy)-5-hydroxybenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%		General procedure: 2,5-Dihydroxybenzaldehyde (1.0 eq.) and cesium carbonate (1.0 eq.) were suspended in DMF and the suspension, warmed to 60 C for 15 min. After cooling down to rt, the corresponding bromide (1.1 eq.) was added in DMF (0.5 M concentration of 2,5-dihydroxybenzaldehyde) and the reaction was stirred at rt for 2h for benzylic haloalkanes or at 60 C overnight for aliphatic haloalkanes. The solvents were evaporated and the crude dissolved in water and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3x) and the combined organic layers were dried over magnesium sulfate, filtered and the solvent evaporated. The crude product was purified by flash chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

81
[ 1194-98-5 ]
[ 655225-01-7 ]
tert-butyl 4-(2-(2-formyl-4-hydroxyphenoxy)ethyl)piperazine-1-carboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%		General procedure: 2,5-Dihydroxybenzaldehyde (1.0 eq.) and cesium carbonate (1.0 eq.) were suspended in DMF and the suspension, warmed to 60 °C for 15 min. After cooling down to rt, the corresponding bromide (1.1 eq.) was added in DMF (0.5 M concentration of 2,5-dihydroxybenzaldehyde) and the reaction was stirred at rt for 2h for benzylic haloalkanes or at 60 °C overnight for aliphatic haloalkanes. The solvents were evaporated and the crude dissolved in water and ethyl acetate. The aqueous phase was extracted with ethyl acetate (3x) and the combined organic layers were dried over magnesium sulfate, filtered and the solvent evaporated. The crude product was purified by flash chromatography.

Reference： [1]Bioorganic and Medicinal Chemistry,2019,vol. 27

82
[ 7504-94-1 ]
[ 1194-98-5 ]
(E)-2-((2-(pyrimidin-2-yl)hydrazono)methyl)benzene-1,4-diol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
69%	In ethanol; at 20℃;	General procedure: Compounds 2 were prepared by the reaction between <strong>[7504-94-1]2-hydrazinylpyrimidine</strong> 1 (0.04 g, 0.36 mmol) and the appropriate aromatic or heteroaromatic aldehyde (1.0 eq., 0.36 mmol) in ethanol (3.0 mL) [27]. The reaction mixture was stirred for between 20 min and 5 h at room temperature. After rotary evaporation, the product was purified by washing with cold ethanol (2.0 mL) and cold diethyl ether (2.0 mL), leading to the pure derivatives 2a-f as solid in 27-75% yields.

Reference： [1]European Journal of Medicinal Chemistry,2019,vol. 184

83
[ 1194-98-5 ]
[ 7474-78-4 ]
2-(2,5-dihydroxyphenyl)-1H-benzo[d]imidazole-5-sulfonic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With sodium metabisulfite; In ethanol; water; for 24h;Reflux;	General procedure: To a solution of the appropriate 3,4-diaminobenzene derivative (1ad)(2 mmol) in ethanol (15 mL) 2.85 N aqueous solution of sodium metabisulphite (1.6 mL) and the appropriate substituted arylaldehyde(2 mmol) were added. The reaction mixture was heated at reflux for 24 h. The solvent was then evaporated under reduced pressure. The residue was added with HCl 1 N (10 mL), the formed precipitate was filtered off, washed with water (3×10 mL) and purified by crystallization from the adequate solvent to give the title compounds.Following the general procedure benzimidazoles 3 [19], 4 [20], 5 [21],7 [24], 6, 32 and 33 [15] were prepared and their analytical and spectral data are in agreement with those reported in literature.

Reference： [1]Bioorganic Chemistry,2019

84
[ 111-16-0 ]
[ 1194-98-5 ]
C₂₁H₂₀O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66.7%	With dmap; diisopropyl-carbodiimide In chloroform at 0 - 25℃; for 20h; Inert atmosphere;	4.1 Step 1: Synthesis of Intermediate H (Still Another Example of the Compound Represented by the Formula (X-1)) 10 g (62.4 mmol) of pimelic acid, 17.2 g (124.9 mmol) of 2,5-dihydroxybenzaldehyde, and 757 mg (6.2 mmol) of N-N-dimethylaminopyridine were added to 250 ml of chloroform in a three-necked reactor equipped with a thermometer under a nitrogen stream. The solution was placed in an ice bath and cooled to 0° C., and then, 18.9 g (149.9 mmol) of N-N′-diisopropylcarbodiimide was added thereto. Then, the solution was stirred at 25° C. for 20 hours. After completion of the reaction, 500 ml of distilled water and 100 ml of saturated saline solution were added to the obtained reaction solution, followed by extraction twice with 300 ml of chloroform. The organic layer was collected, and dried with anhydrous sodium sulfate, and the sodium sulfate was filtered off. The concentration of the obtained organic layer was adjusted by evaporating the solvent using the rotary evaporator. 500 ml of methanol was added to the solution to precipitate a solid, and the produced solid was filtered off. The obtained filtered matter was charged into 500 ml of methanol, and was stirred and washed for 1 hour at room temperature. The filtration was performed again, and the filtered matter washed in 500 ml of methanol to obtain 16.7 g of Intermediate H as a white solid. The yield was 66.7 mol %. The structure of Intermediate H was identified by 1H-NMR. The 1H-NMR spectral data is presented below. (0413) 1H-NMR (500 MHz, CDCl3, TMS, δppm): 10.91 (s, 2H), 9.83 (s, 2H), 7.32 (d, 2H, J=3.0 Hz), 7.24 (dd, 2H, J=3.0 Hz, 9.0 Hz), 7.00 (d, 2H, J=9.0 Hz), 2.62 (t, 4H, J=7.5 Hz), 1.86-1.80 (m, 4H), 1.59-1.53 (m, 2H).
16.7 g	With dmap; diisopropyl-carbodiimide In chloroform at 0 - 25℃; for 20h; Inert atmosphere;	9 (Synthesis Example 9) Synthesis of Compound K (Another Example of a Compound Represented by Formula (II)) 10 g (62.4 mmol) of pimelic acid, 17.2 g (124.9 mmol) of 2,5-dihydroxybenzaldehyde, and 757 mg (6.2 mmol) of N-N-dimethylaminopyridine were added to 250 ml of chloroform 250 ml in a three-necked reactor equipped with a thermometer under a nitrogen stream. The solution was placed in a water bath and cooled to 0° C., and then, 18.9 g (149.9 mmol) of N-N′-diisopropylcarbodiimide was added thereto. Then, the solution was stirred at 25° C. for 20 hours. after completion of the reaction, 500 ml of distilled water and 100 ml of saturated saline solution were added to the obtained reaction solution, followed by extraction twice with 300 ml of chloroform. The organic layer was collected, dried with anhydrous sodium sulfate, and the sodium sulfate was filtered off. The concentration of the obtained organic layer was adjusted by evaporating the solvent by the rotary evaporator. 500 ml of methanol was added to the solution to precipitate a solid, and the produced solid was filtered off. The obtained filtered matter was charged into 500 ml of methanol, and was stirred and washed for 1 hour at room temperature. The filtration was performed again, and the filtered matter washed in 500 ml of methanol to obtain 16.7 g of the compound K as a white solid. The yield was 66.7 mol %. The structure of the target product (compound K) was identified by 1H-NMR. The 1H-NMR spectral data is shown below. 1H-NMR (500 MHz, CDCl3, TMS, δ ppm): 10.91 (s, 2H), 9.83 (s, 2H), 7.32 (d, 2H, J=3.0 Hz), 7.24 (dd, 2H, J=3.0 Hz, 9.0 Hz), 7.00 (d, 2H, J=9.0 Hz), 2.62 (t, 4H, J=7.5 Hz), 1.86-1.80 (m, 4H), 1.59-1.53 (m, 2H).

Reference： [1]Current Patent Assignee: ZEON CORPORATION - US2020/31786, 2020, A1 Location in patent: Paragraph 0411-0413
[2]Current Patent Assignee: ZEON CORPORATION - US2020/283399, 2020, A1 Location in patent: Paragraph 0373-0375

85
[ 505-48-6 ]
[ 1194-98-5 ]
C₂₂H₂₂O₈ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
58.2%	With dmap; diisopropyl-carbodiimide In chloroform at 0 - 25℃; for 20h; Inert atmosphere;	5.1 Step 1: Synthesis of Intermediate J (Still Another Example of the Compound Represented by the Formula (X-1)) 10 g (57.4 mmol) of 1,6-hexanedicarboxylic acid, 15.9 g (114.8 mmol) of 2,5-dihydroxybenzaldehyde, and 696 mg (5.7 mmol) of N-N-dimethylaminopyridine were added to 250 ml of chloroform in a three-necked reactor equipped with a thermometer under a nitrogen stream. The solution was placed in an ice bath and cooled to 0° C., and then, 17.4 g (137.8 mmol) of N-N′-diisopropylcarbodiimide was added thereto. Then, the solution was stirred at 25° C. for 20 hours. after completion of the reaction, 500 ml of distilled water and 100 ml of saturated saline solution were added to the obtained reaction solution, followed by extraction twice with 300 ml of chloroform. The organic layer was collected, and dried with anhydrous sodium sulfate, and the sodium sulfate was filtered off. The concentration of the obtained organic layer was adjusted by evaporating the solvent using a rotary evaporator. 500 ml of methanol was added to the solution to precipitate a solid, and the produced solid was filtered off. The obtained filtered matter was charged into 500 ml of methanol, and was stirred and washed for 1 hour at room temperature. The filtration was performed again, and the filtered matter washed in 500 ml of methanol to obtain 13.8 g of Intermediate J as a gray solid. The yield was 58.2 mol %. The structure of Intermediate J was identified by 1H-NMR. The 1H-NMR spectral data is presented below. (0423) 1H-NMR (500 MHz, CDCl3, TMS, δppm): 10.91 (s, 2H), 9.85 (s, 1H), 9.85 (s, 1H), 7.32 (d, 2H, J=2.5 Hz), 7.24 (dd, 2H, J=2.5 Hz, 9.0 Hz), 7.00 (d, 2H, J=9.0 Hz), 2.59 (t, 4H, J=7.5 Hz), 1.81-1.78 (m, 4H), 1.51-1.48 (m, 4H).
13.8 g	With dmap; diisopropyl-carbodiimide In chloroform at 0 - 25℃; for 20h; Inert atmosphere;	10 (Synthesis Example 10) Synthesis of Compound L (Another Example of a Compound Represented by Formula (II)) 10 g (57.4 mmol) of 1,6-hexanedicarboxylic acid, 15.9 g (114.8 mmol) of 2,5-dihydroxybenzaldehyde, and 696 mg (5.7 mmol) of N-N-dimethylaminopyridine were added to 250 ml of chloroform in a three-necked reactor equipped with a thermometer under a nitrogen stream. The solution was placed in a water bath and cooled to 0° C., and then, 17.4 g (137.8 mmol) of N-N′-diisopropylcarbodiimide was added thereto. Then, the solution was stirred at 25° C. for 20 hours. after completion of the reaction, 500 ml of distilled water and 100 ml of saturated saline solution were added to the obtained reaction solution, followed by extraction twice with 300 ml of chloroform. The organic layer was collected, dried with anhydrous sodium sulfate, and the sodium sulfate was filtered off. The concentration of the obtained organic layer was adjusted by evaporating the solvent by the rotary evaporator. 500 ml of methanol was added to the solution to precipitate a solid, and the produced solid was filtered off. The obtained filtered matter was charged into 500 ml of methanol, and was stirred and washed for 1 hour at room temperature. The filtration was performed again, and the filtered matter washed in 500 ml of methanol to obtain 13.8 g of the compound L as gray solid. The yield was 58.2 mol %. The structure of the target product (compound L) was identified by 1H-NMR. The 1H-NMR spectral data is shown below. 1H-NMR (500 MHz, CDCl3, TMS, δ ppm): 10.91 (s, 2H), 9.85 (s, 1H), 9.85 (s, 1H), 7.32 (d, 2H, J=2.5 Hz), 7.24 (dd, 2H, J=2.5 Hz, 9.0 Hz), 7.00 (d, 2H, J=9.0 Hz), 2.59 (t, 4H, J=7.5 Hz), 1.81-1.78 (m, 4H), 1.51-1.48 (m, 4H).

Reference： [1]Current Patent Assignee: ZEON CORPORATION - US2020/31786, 2020, A1 Location in patent: Paragraph 0421-0423
[2]Current Patent Assignee: ZEON CORPORATION - US2020/283399, 2020, A1 Location in patent: Paragraph 0376-0378

86
[ 1194-98-5 ]
[ 939-99-1 ]
[ 1311393-11-9 ]

Yield	Reaction Conditions	Operation in experiment
56%	With potassium carbonate In acetonitrile at 80℃; for 5h;	3.1.1. General Procedure for Synthesis of Intermediate Compounds 3a-c General procedure: Potassium carbonate (1.5 mmol) was added to a solution of aldehyde (1.0 mmol) withdifferent substituents and benzyl chloride (1.0 mmol) with different substituents or 1-(2-chloroethyl)-4-trifluoromethylbenzene (1.0 mmol) in acetonitrile (15 mL). The mixturewas heated to 80 °C for 5 h. After the reaction was complete and the solvent was spindriedunder reduced pressure, the mixture was diluted with water (20 mL) and extractedwith ethyl acetate (60 mL), and the organic layer was separated and dried over anhydroussodium sulfate. After the evaporation of solvent under reduced pressure, the crude productwas purified on a silica gel column to produce compounds 3a-c as a white solid.

Reference： [1]Huang, Ling; Huang, Yi-You; Huang, Yue; Li, Jinjian; Li, Zhe; Luo, Hai-Bin; Su, Rui; Wu, Yinuo; Yuan, Han; Zhang, Chen; Zhou, Yan [Molecules, 2021, vol. 26, # 10]

87
[ 1194-98-5 ]
[ 38289-27-9 ]
(3-methanoyl-4-hydroxyphenyl) 4-propylcyclohexylcarboxylate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
45%	With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 20℃; for 22h;	To 2,5-dihydroxybenzaldehyde (1.38 g, 10 mmol),Trans-4-propylcyclohexane-carboxylic acid (1.79 g, 10.5 mmol) and 4-dimethylaminopyridine (DMAP) (122 mg, 1 mmol)Slowly add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDC) (1.94 mL, 11 mmol) to a solution in dry dichloromethane (20 mL).The reaction mixture was stirred at ambient temperature for 22 hours. The reaction mixture was quenched with saturated aqueous sodium bicarbonate and extracted with dichloromethane. The organic phase was washed with brine, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure.The residue was purified by silica gel flash column chromatography using ethyl acetate/hexane to give the title compound (1.31 g, 45%) as a yellow solid.

Reference： [1]Patent: TW2021/12748,2021,A .Location in patent: Paragraph 0071-0073

88
[ 1194-98-5 ]
[ 29182-42-1 ]
3-(benzo[d]thiazol-2-yl)-6-methoxy-2H-chromen-2-one [ No CAS ]

Reference： [1]Journal of Physical Chemistry B,2021,vol. 125,p. 11557 - 11565

89
[ 1194-98-5 ]
[ 29182-42-1 ]
[ 1144500-79-7 ]

Reference： [1]Journal of Physical Chemistry B,2021,vol. 125,p. 11557 - 11565

Purity	Size	Price	VIP Price	USA Stock *0-1 Day	Global Stock *5-7 Days	Quantity
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CAS No. :	1194-98-5	MDL No. :
Formula :	C₇H₆O₃	Boiling Point :	-
Linear Structure Formula :	-	InChI Key :	CLFRCXCBWIQVRN-UHFFFAOYSA-N
M.W :	138.12	Pubchem ID :	70949
Synonyms :	Gentisaldehyde;5-Hydroxysalicylaldehyde;NSC 72387

Num. heavy atoms :	10
Num. arom. heavy atoms :	6
Fraction Csp3 :	0.0
Num. rotatable bonds :	1
Num. H-bond acceptors :	3.0
Num. H-bond donors :	2.0
Molar Refractivity :	35.88
TPSA :	57.53 Å²

GI absorption :	High
BBB permeant :	Yes
P-gp substrate :	No
CYP1A2 inhibitor :	No
CYP2C19 inhibitor :	No
CYP2C9 inhibitor :	No
CYP2D6 inhibitor :	No
CYP3A4 inhibitor :	Yes
Log Kp (skin permeation) :	-6.76 cm/s

Log Po/w (iLOGP) :	0.7
Log Po/w (XLOGP3) :	0.54
Log Po/w (WLOGP) :	0.91
Log Po/w (MLOGP) :	0.18
Log Po/w (SILICOS-IT) :	1.02
Consensus Log Po/w :	0.67

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[ 1194-98-5 ] Synthesis Path-Upstream 1~3

[ 1194-98-5 ] Synthesis Path-Downstream 1~89

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[ 1194-98-5 ]

Aryls

Aldehydes

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Lipinski :	0.0
Ghose :	None
Veber :	0.0
Egan :	0.0
Muegge :	1.0
Bioavailability Score :	0.55

Log S (ESOL) :	-1.41
Solubility :	5.32 mg/ml ; 0.0385 mol/l
Class :	Very soluble
Log S (Ali) :	-1.32
Solubility :	6.62 mg/ml ; 0.0479 mol/l
Class :	Very soluble
Log S (SILICOS-IT) :	-1.17
Solubility :	9.4 mg/ml ; 0.0681 mol/l
Class :	Soluble

PAINS :	0.0 alert
Brenk :	2.0 alert
Leadlikeness :	1.0
Synthetic accessibility :	1.0

Signal Word:	Warning	Class:	N/A
Precautionary Statements:	P261-P280-P305+P351+P338	UN#:	N/A
Hazard Statements:	H315-H317-H319-H335	Packing Group:	N/A
GHS Pictogram:

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P378
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P391	Collect spillage. Hazardous to the aquatic environment
P301 + P310	IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P301 + P312	IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.
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P302 + P350	IF ON SKIN: Gently wash with plenty of soap and water.
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P333 + P313	IF SKIN irritation or rash occurs: Get medical advice/attention.
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P337 + P313	IF eye irritation persists: Get medical advice/attention.
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P370 + P376	In case of fire: Stop leak if safe to Do so.
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Calculated chemistry of [ 1194-98-5 ]

Physicochemical Properties

Pharmacokinetics

Lipophilicity

Druglikeness

Water Solubility

Medicinal Chemistry

Safety of [ 1194-98-5 ]

Application In Synthesis of [ 1194-98-5 ]

[ 1194-98-5 ] Synthesis Path-Upstream 1~3

[ 1194-98-5 ] Synthesis Path-Downstream 1~89

Related Functional Groups of [ 1194-98-5 ]

Aryls

Aldehydes

Precautionary Statements-General

Prevention

Response

Storage

Disposal

Physical hazards

Health hazards

Environmental hazards

Inquiry

Related Functional Groups of
[ 1194-98-5 ]