Name: 1927-94-2|3-Chloro-2-hydroxybenzaldehyde|98%
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SKU: A107494
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1
[ 22471-02-9 ]
[ 127-68-4 ]
[ 1927-94-2 ]

Reference： [1]Journal fur praktische Chemie (Leipzig 1954),1941,vol. <2> 158,p. 245,250

2
[ 1829-32-9 ]
[ 1927-94-2 ]

Reference： [1]Chemische Berichte,1908,vol. 41,p. 4147
Chemisches Zentralblatt,1908,vol. 79,p. 1504
[2]Patent: DE228838,
Fortschr. Teerfarbenfabr. Verw. Industriezweige,vol. 10,p. 217

3
[ 1927-94-2 ]
[ 74-88-4 ]
[ 223778-54-9 ]

Reference： [1]European Journal of Organic Chemistry,2003,p. 2566 - 2576
[2]Journal of the Chemical Society,1923,vol. 123,p. 2850
[3]European Journal of Organic Chemistry,2016,vol. 2016,p. 3679 - 3683

4
[ 67-66-3 ]
[ 95-57-8 ]
[ 1927-94-2 ]

Yield	Reaction Conditions	Operation in experiment
58%	With sodium hydroxide In ethanol for 0.0666667h; Irradiation;
	(i) aq. NaOH, (ii) /BRN= 1731042/; Multistep reaction;
	With sodium hydroxide In ethanol; water for 1h; Heating;

	With sodium hydroxide In ethanol for 1h; Heating;
	With sodium hydroxide for 2h; Reflux;

Reference： [1]Vibhute, Yeshwant B.; Lonkar, Subhash M.; Sayyed, Mudassar A.; Baseer, Mohammad A. [Mendeleev Communications, 2007, vol. 17, # 1, p. 51 - 51]
[2]Dandegaonker,S.H.; Revankar,G.R. [Monatshefte fur Chemie, 1965, vol. 96, p. 450 - 460]
[3]Lai, Guoyin; Wang, Sujing; Wang, Zhiyong [Tetrahedron Asymmetry, 2008, vol. 19, # 15, p. 1813 - 1819]
[4]Zhang, Zuhui; Pan, Chongfeng; Wang, Zhiyong [Chemical Communications, 2007, # 44, p. 4686 - 4688]
[5]Bouchmaa, Najat; Ben Mrid, Reda; Boukharsa, Youness; Nhiri, Mohamed; Ait Mouse, Hassan; Taoufik, Jamal; Ansar, M'hammed; Zyad, Abdelmajid [Archiv der Pharmazie, 2018, vol. 351, # 12]

5
[ 1927-94-2 ]
[ 1829-32-9 ]

Reference： [1]Monatshefte fur Chemie,1965,vol. 96,p. 450 - 460

6
[ 50-00-0 ]
[ 95-57-8 ]
[ 1927-94-2 ]

Yield	Reaction Conditions	Operation in experiment
87%	With triethylamine; magnesium chloride In acetonitrile for 3.5h; Heating;
87%	Stage #1: formaldehyd With triethylamine; magnesium chloride In tetrahydrofuran for 0.166667h; Inert atmosphere; Stage #2: 2-monochlorophenol In tetrahydrofuran at 75℃; Inert atmosphere; regioselective reaction;
80%	With triethylamine; magnesium chloride In acetonitrile for 4h; Reflux;	99 Preparation example 99 ·^' 3-chloro-2-hydroxybenzaldehyde Preparation example 99 ·' 3-chloro-2-hydroxybenzaldehyde To a stirred solution of 2-chlorophenol (20. Og, 155.60mmol) in acetonitrile (200mL) was added MgCl2 (22.2g, 233.35mmol) and tr iethylamine (59.03 g, 583.39mmo 1 ) at room temperature. The mixture was added paraformaldehyde^ .52g, 1.05mol) then refluxed for 4hr. The resulting mixture was cooled to room temperature, quenched with 2N HC1, extracted with ether, dried over MgS04, filtered and concentrated under reduced pressure. The crude compound was purified by silica gel column chromatography to obtain the title compound. (16.7g, 60-80%) H NMR (400MHz, CDC13) δ 7.01 (t, J=7.8, 1H), 7.49-7.56 (m, 1H), 7.63 (d, .7=8.0, 1H), 9.91 (s, 1H), 11.50 (s, 1H).

69%	Stage #1: 2-monochlorophenol With triethylamine; magnesium chloride In acetonitrile at 20℃; for 0.25h; Stage #2: formaldehyd In acetonitrile Reflux;
54%	With triethylamine; magnesium chloride In tetrahydrofuran	11.Q Boc-T115 has been prepared from 2-chlorophenol (115-1) and (S)-ethyl lactate (115-0) using the multi-step procedure shown.TLC: Rf=0.45 [Hexanes/MTBE (3:7)], detection: UV+Mo/Ce1H NMR (CDCl3): δ 7.23-7.20, (m, 1H), 7.01-7.07, (m, 1H), 7.02-6.95 (m, 1H), 5.15-4.93 (bs, 1H), 4.58-4.49 (m, 1H), 3.91-3.86 (dd, 1H), 3.77-3.71 (dd, 1H), 3.17-3.07 (m, 1H), 3.03-2.94 (m, 1H), 2.86-2.73 (q, 1H), 2.72-2.61 (q, 1H), 2.22-2.00 (bs, 1H), 1.84-1.65 (m, 2H), 1.45 (s, 9H), 1.24-1.19 (d, 3H).Use of (R)-ethyl lactate in the second step provides the enantiomeric tether, T115b. Alternative ester groups compatible with the reaction sequence can be similarly employed.
	With tributyl-amine 1.) toluene, room temperature, 20 min, 2.) 100 deg C, 8 h; Yield given. Multistep reaction;
	With triethylamine; magnesium chloride In tetrahydrofuran Heating;
	With triethylamine; magnesium chloride In tetrahydrofuran Heating;
	With tributyl-amine; tin(IV) chloride In toluene at 100℃; for 10h; Inert atmosphere;
	With triethylamine; magnesium chloride In tetrahydrofuran at 80℃; for 8h;
	With triethylamine; magnesium chloride In tetrahydrofuran for 24h; Reflux; Inert atmosphere;
	With triethylamine; magnesium chloride In tetrahydrofuran for 24h; Inert atmosphere; Reflux;
	With triethylamine; magnesium chloride In tetrahydrofuran for 24h; Inert atmosphere; Reflux;

Reference： [1]Hofslokken, Nini U.; Skattebol, Lars [Acta Chemica Scandinavica, 1999, vol. 53, # 4, p. 258 - 262]
[2]Hansen, Trond Vidar; Skattebøl, Lars; Guthrie, David; Curran, Dennis P. [Organic Syntheses, 2005, vol. 82, p. 64 - 68]
[3]Current Patent Assignee: BIO-PHARM SOLUTIONS CO LTD - WO2015/88272, 2015, A1 Location in patent: Page/Page column 67
[4]Chen, Wei; Zhou, Zhao-Hui; Chen, Hong-Bin [Organic and Biomolecular Chemistry, 2017, vol. 15, # 6, p. 1530 - 1536]
[5]Current Patent Assignee: MALLINCKRODT PUBLIC LIMITED COMPANY - US2008/194672, 2008, A1 Location in patent: Page/Page column 48-49
[6]Casiraghi, Giovanni; Casnati, Giuseppe; Puglia, Giuseppe; Sartori, Giovanni; Terenghi, Giuliana [Journal of the Chemical Society. Perkin transactions I, 1980, p. 1862 - 1865]
[7]Hansen, Trond Vidar; Skattebøl, Lars [Tetrahedron Letters, 2005, vol. 46, # 19, p. 3357 - 3358] Anwar, Hany F.; Skattebøl, Lars; Skramstad, Jan; Hansen, Trond Vidar [Tetrahedron Letters, 2005, vol. 46, # 32, p. 5285 - 5287]
[8]Anwar, Hany F.; Skattebøl, Lars; Hansen, Trond Vidar [Tetrahedron, 2007, vol. 63, # 40, p. 9997 - 10002]
[9]Location in patent: scheme or table Jia, Ai-Quan; Jin, Guo-Xin [Dalton Transactions, 2009, # 41, p. 8838 - 8845]
[10]Nakai, Yuhta; Moriyama, Katsuhiko; Togo, Hideo [European Journal of Organic Chemistry, 2014, vol. 2014, # 27, p. 6077 - 6083]
[11]Mao, Biming; Shi, Wangyu; Liao, Jianning; Liu, Honglei; Zhang, Cheng; Guo, Hongchao [Organic Letters, 2017, vol. 19, # 23, p. 6340 - 6343]
[12]Wang, Chang; Li, Yan; Wu, Yang; Wang, Qijun; Shi, Wangyu; Yuan, Chunhao; Zhou, Leijie; Xiao, Yumei; Guo, Hongchao [Organic Letters, 2018, vol. 20, # 10, p. 2880 - 2883]
[13]Shi, Wangyu; Zhou, Leijie; Mao, Biming; Wang, Qijun; Wang, Chang; Zhang, Cheng; Li, Xuefeng; Xiao, Yumei; Guo, Hongchao [Journal of Organic Chemistry, 2019, vol. 84, # 2, p. 679 - 685]

7
[ 1927-94-2 ]
[ 108-24-7 ]
[ 33491-29-1 ]

Yield	Reaction Conditions	Operation in experiment
88%	at 175℃; for 6h; Acidic conditions;	Step 1: 8-chloro-2H-chromen-2-one A mixture of 3-chloro-2-hydroxybenzaldehyde (1 g, 6.4 mmol) and CH3COOH (1.3 g, 12.8mmol) in Ac20 (45 mL) was heated to 175 °C for 6 hrs. The mixture was then cooled down to rt. The precipitate which formed was collected to give 8-chloro-2H-chromen-2-one (1.02 g, 88%) as a brown solid. ESI-MS (EI+, m/z): 181.0 [M+l]+.
88%	at 175℃; for 6h; Acidic conditions;	Step 1: 8-chloro-2H-chromen-2-one A mixture of 3-chloro-2-hydroxybenzaldehyde (1 g, 6.4 mmol) and CH3COOH (1.3 g, 12.8mmol) in Ac20 (45 mL) was heated to 175 °C for 6 hrs. The mixture was then cooled down to rt. The precipitate which formed was collected to give 8-chloro-2H-chromen-2-one (1.02 g, 88%) as a brown solid. ESI-MS (EI+, m/z): 181.0 [M+l]+.
54%	With sodium acetate at 180 - 190℃; for 18h;

	With sodium acetate at 185℃; for 6h; Inert atmosphere;
	With sodium acetate at 170℃; for 6h; Inert atmosphere; Sealed tube;
	With sodium acetate at 185℃; for 6h; Inert atmosphere;	(a) General procedure for synthesis of coumarins General procedure: To a stirred solution of salicylaldehyde (8.19 mmol) in acetic anhydride (1.67 g, 16.32 mmol)was added sodium acetate (1.33 g, 16.32 mmol) under nitrogen. The resulting mixture was heatedto 185 oC and then stirred for 6 h. After cooling, the reaction mixture was quenched with water (15mL) and extracted with ethyl acetate (30 mL). The organic layer was washed with brine (2×50mL), dried with Na2SO4, and concentrated under reduced pressure. The crude product was purifiedby chromatography on a silica gel column to afford the coumarins 1 (0 → 25% ethylacetate/hexane).

Reference： [1]Current Patent Assignee: DISCOVERYBIOMED INC - WO2014/152213, 2014, A2 Location in patent: Page/Page column 48
[2]Current Patent Assignee: DISCOVERYBIOMED INC - WO2014/152278, 2014, A2 Location in patent: Page/Page column 47
[3]Hepworth, John D.; Jones, Terry K.; Livingstone, Robert [Tetrahedron, 1981, vol. 37, # 15, p. 2613 - 2616]
[4]Jin, Can; Yan, Zhiyang; Sun, Bin; Yang, Jin [Organic Letters, 2019, vol. 21, # 7, p. 2064 - 2068]
[5]Chen, Zhiwei; Bai, Xiang; Sun, Jie; Xu, Yicheng [Journal of Organic Chemistry, 2020, vol. 85, # 12, p. 7674 - 7682]
[6]Jin, Can; Sun, Bin; Xu, Tengwei; Yan, Zhiyang; Zhang, Xun [Synlett, 2019, vol. 30, # 13, p. 1585 - 1591]

8
[ 1927-94-2 ]
[ 2892-29-7 ]
[ 15934-92-6 ]

Reference： [1]Monatshefte fur Chemie,1965,vol. 96,p. 1214 - 1223

9
[ 1927-94-2 ]
[ 2032-35-1 ]
[ 179728-61-1 ]

Yield	Reaction Conditions	Operation in experiment
82%	With potassium carbonate In N,N-dimethyl-formamide for 4h; Heating;
	With potassium carbonate In N,N-dimethyl-formamide for 4h; Reflux;

Reference： [1]Ansar; Al Akoum Ebrik; Mouhoub; Berthelot; Vaccher; Vaccher; Flouquet; Caignard; Renard; Pirard; Rettori; Evrard; Durant; Debaert [European Journal of Medicinal Chemistry, 1996, vol. 31, # 6, p. 449 - 460]
[2]Bouchmaa, Najat; Ben Mrid, Reda; Boukharsa, Youness; Nhiri, Mohamed; Ait Mouse, Hassan; Taoufik, Jamal; Ansar, M'hammed; Zyad, Abdelmajid [Archiv der Pharmazie, 2018, vol. 351, # 12]

11
[ 1927-94-2 ]
[ 4018-65-9 ]

Reference： [1]RSC Advances,2015,vol. 5,p. 105583 - 105586
[2]Organic Letters,2012,vol. 14,p. 5150 - 5153,4
[3]Tetrahedron Letters,2005,vol. 46,p. 3357 - 3358

12
[ 1927-94-2 ]
[ 104-83-6 ]
3-chloro-2-((4-chlorobenzyl)oxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
99.3%	With potassium carbonate In N,N-dimethyl-formamide at 120℃; for 2h; Inert atmosphere;	2 4.2.2. General procedure for the synthesis of 3a-3k General procedure: To a solution of substituted salicylaldehyde (1.0 mmol) in anhydrousDMF was added 4-chlorobenzyl chloride (139 lL, 1.1 mmol),K2CO3 (553 mg, 4.0 mmol). The reaction mixture was stirred at120 C for 2 h and monitored by LC/MS analysis. Upon completion the mixture was cooled to room temperature. Water and ethylacetate were added and the mixture was extracted with ethyl acetatetwice. The combined extracts were washed with water andbrine, dried over Na2SO4. After filtration, the filtrate was removedin vacuo. The residue was purified by silica gel column chromatographyto give 3a-3k (75.0-99.0%).
	With caesium carbonate In N,N-dimethyl-formamide at 60℃; for 2h;

Reference： [1]Gao, Dingding; Xiao, Qiang; Zhang, Mingming; Li, Yingxia [Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 11, p. 2549 - 2558]
[2]Wei, Robert G.; Arnaiz, Damian O.; Chou, Yuo-Ling; Davey, Dave; Dunning, Laura; Lee, Wheeseong; Lu, Shou-Fu; Onuffer, James; Ye, Bin; Phillips, Gary [Bioorganic and Medicinal Chemistry Letters, 2007, vol. 17, # 1, p. 231 - 234]

13
[ 1927-94-2 ]
[ 67-64-1 ]
[ 1019769-53-9 ]

Yield	Reaction Conditions	Operation in experiment
	In water at 0 - 20℃; for 19.1667h;	16 Preparation 16; 4-(3-Chloro-2-hvdroxyphenvHbut-3-en-2-one; To a solution of the compound of Preparation 108 (17.5 g, 112.0 mmol) in acetone (49 ml), at 0°C, was added aqueous sodium hydroxide solution (5M, 33 ml) over 10 min. The reaction mixture was stirred at 0°C for 60 min and then at room temperature for 18 h. To the mixture was added water (500 ml) and the solution was extracted with dichloromethane (100 ml). The aqueous phase was acidified with excess aqueous citric acid solution and the resulting precipitate was collected by filtration. The solid was washed with water (100 ml), aqueous sodium hydrogen carbonate solution (100 ml), aqueous sodium metabisulfite solution (100 ml) and additional water (3 x 100 ml) and air dried to give the title compound (2O g) 1H-NMR (CDCI3): 2.39 - 2.41 (3H), 6.78 - 6.93 (2H), 7.34 - 7.38 (1 H), 7.41 - 7.46 (1 H), 7.77 - 7.83 (1 H)

Reference： [1]Current Patent Assignee: PFIZER INC - WO2008/44127, 2008, A1 Location in patent: Page/Page column 81

14
[ 1927-94-2 ]
[ 37435-12-4 ]

Yield	Reaction Conditions	Operation in experiment
	With hydrazine hydro-chloride; In ethanol; for 3h;Reflux;	General procedure: To a solution of 2-hydroxy-3-methylbenzaldehyde (5 g, 36.7 mmol) inEtOH (30 mL) was added hydrazine hydrochloride (in excess) in a 250 mL flask. The solution was refluxed for 3 h and the solvent was distilled under reduced pressure. Purification of the residue by column chromatography (EtOAc:PE=10:1) on silica gel was performed to give 3.5 g of 7-methyl-1H-indazole, yellow crystals (73% yield).

Reference： [1]Tetrahedron Letters,2007,vol. 48,p. 6890 - 6892
[2]Heterocycles,2018,vol. 96,p. 74 - 85

15
[ 1927-94-2 ]
[ 24410-55-7 ]

Reference： [1]Bioorganic and Medicinal Chemistry Letters,2000,vol. 10,p. 71 - 74
[2]Gazzetta Chimica Italiana,1955,vol. 85,p. 381,388

16
[ 1927-94-2 ]
[ 3260-93-3 ]

Reference： [1]Journal of the Chemical Society,1923,vol. 123,p. 2850

17
[ 1927-94-2 ]
[ 75-03-6 ]
[ 709649-70-7 ]

Yield	Reaction Conditions	Operation in experiment
91%	With potassium carbonate In DMF (N,N-dimethyl-formamide) at 20 - 50℃; for 20.5h;	VII.a; 39.a Preparation 39; Preparation of (3-CHORO-2-ETHOX.-BENZYLHNETHYLAMINE; a) 3-Chloro-2-ethoxy-benzaldehyde; Scheme VII LODOETHANE (1.54 mL, 19.2 mmol) was added to a stirring solution of 3-chloro-2- hydroxy-benzaldehyde (2.01 g, 12.8 mmol) and K2CO3 (3.90 g, 28.2 mmol) in DMF (25 mL). The mixture was heated to 50 °C and stirred for 2.5 h. The heat was removed and reaction stirred at room temperature for 18 h. The reaction was quenched with H2O (70 mL). The mixture was extracted with EtOAc (3 x 50 mL). The combined organics were washed with brine (2 x 50 mL), dried over NA2SO4, filtered and concentrated to yield the title compound (2.16 g, 91%) as a yellow oil : 1H NMR (300 MHz, DMSO-d6) 8 10. 27 (s, 1H), 7. 85 (dd, J= 7.8, 1. 5 HZ, 1 H), 7.72 (dd, J = 7. 8,1. 8 Hz, 1H), 7. 33 (t, J = 7.8 Hz, 1H), 4.14 (q, J= 7.2 Hz, 2H), 1.39 (t, J= 6.9 Hz, 3H).

Reference： [1]Current Patent Assignee: DEBIOPHARM INTERNATIONAL SA - WO2004/52890, 2004, A1 Location in patent: Page 47; 90

18
[ 687-47-8 ]
[ 1927-94-2 ]
[ 1047665-06-4 ]

Yield	Reaction Conditions	Operation in experiment
61%	With di-isopropyl azodicarboxylate; triphenylphosphine In tetrahydrofuran	11.Q Boc-T115 has been prepared from 2-chlorophenol (115-1) and (S)-ethyl lactate (115-0) using the multi-step procedure shown.TLC: Rf=0.45 [Hexanes/MTBE (3:7)], detection: UV+Mo/Ce1H NMR (CDCl3): δ 7.23-7.20, (m, 1H), 7.01-7.07, (m, 1H), 7.02-6.95 (m, 1H), 5.15-4.93 (bs, 1H), 4.58-4.49 (m, 1H), 3.91-3.86 (dd, 1H), 3.77-3.71 (dd, 1H), 3.17-3.07 (m, 1H), 3.03-2.94 (m, 1H), 2.86-2.73 (q, 1H), 2.72-2.61 (q, 1H), 2.22-2.00 (bs, 1H), 1.84-1.65 (m, 2H), 1.45 (s, 9H), 1.24-1.19 (d, 3H).Use of (R)-ethyl lactate in the second step provides the enantiomeric tether, T115b. Alternative ester groups compatible with the reaction sequence can be similarly employed.

Reference： [1]Current Patent Assignee: MALLINCKRODT PUBLIC LIMITED COMPANY - US2008/194672, 2008, A1 Location in patent: Page/Page column 48-49

19
[ 1927-94-2 ]
[ 17366-80-2 ]
[ 1093349-13-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With tetraethoxy orthosilicate at 140℃; for 8h; Inert atmosphere;

Reference： [1]Meng, Xiangtai; Huang, You; Chen, Ruyu [Organic Letters, 2009, vol. 11, # 1, p. 137 - 140]

20
[ 1199-01-5 ]
[ 1927-94-2 ]
[ 33259-07-3 ]

Yield	Reaction Conditions	Operation in experiment
90%	With 1-butyl-3-methylimidazolium hydroxide In acetonitrile at 20℃; for 12h;

Reference： [1]Location in patent: experimental part Yadav, Lal Dhar S.; Singh, Santosh; Rai, Vijai K. [Tetrahedron Letters, 2009, vol. 50, # 19, p. 2208 - 2212]

21
[ 1927-94-2 ]
[ 74268-51-2 ]
C₁₄H₁₅ClO₄ [ No CAS ]
C₁₄H₁₅ClO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With tri(4-chlorophenyl)phosphine In dichloromethane at 20℃; for 41h; Inert atmosphere; optical yield given as %de; diastereoselective reaction;	3.1.1. Phosphine-catalyzed [4+2] annulation of γ-methyl allenoate 1a with salicylaldehydes (typical procedure) (A) Without water additive. At room temperature, to a stirred solution of 5-chloro salicylaldehydes 4i (78 mg, 0.5 mmol) and tris(p-chlorophenyl)phosphine (37 mg, 0.1 mmol) in dichloromethane (5 mL) was added γ-methyl allenoate 1a (95 mg, 0.75 mmol) by the means of a microsyringe over 5 min. The resulting reaction mixture was stirred until the salicylaldehyde was completely consumed (44 h), as monitored by TLC. The solvent was removed on a rotary evaporator under reduced pressure and the residue was subjected to column chromatography isolation on silica gel (gradient eluant: petroleum ether/ethyl acetate 20:1 to 10:1) to afford chromans trans-5i

Reference： [1]Ma, Renqin; Xu, Silong; Tang, Xiaofang; Wu, Guiping; He, Zhengjie [Tetrahedron, 2011, vol. 67, # 6, p. 1053 - 1061]

22
[ 1927-94-2 ]
[ 619-05-6 ]
[ 1313591-68-2 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: 3-chlorosalicylaldehyde With sodium metabisulfite In ethanol; water at 20℃; Stage #2: 3,4-diaminobenzoic acid In N,N-dimethyl-formamide at 130℃;	6.1. General procedures for the preparation of 2-alkylbenzimidazole-5-carbohydrazides (4a-f) and 2-arylbenzimidazole-5-carboxylic acids (6a-l) General procedure: To a solution of substituted benzaldehyde (1.50 mmol) in absolute EtOH (50 mL) was added dropwise sodium pyrosulfite (1.60 g, 8.00 mmol) in water (3 mL). The resulting solution was allowed to stir for 1-3 h at the room temperature and then for 3-4 h at 0 °C. The precipitate was collected and washed with EtOH to provide the addition products (5) as solids in yields ranging from 72% to 83%.A solution of 3,4-diaminobenzoic acid (0.62 g, 4.00 mmol) and the addition products 5 (2.00 mmol) in DMF (5 mL) was stirred at 130 °C for 6-12 h. After the completion of the reaction, the reaction solution was cooled to room temperature and added water (15 mL). The precipitate was collected and washed to give 2-arylbenzimidazole-5-carboxylic acids (6a-l). The yields were within the range of 68-75%. Some of the 2-substituted benzimidazole-5-carboxylic acid derivatives are as followed.

Reference： [1]Cong, Chao; Wang, Haiyang; Hu, Yue; Liu, Chen; Ma, Siti; Li, Xin; Cao, Jichao; Ma, Shutao [European Journal of Medicinal Chemistry, 2011, vol. 46, # 7, p. 3105 - 3111]

23
[ 1927-94-2 ]
[ 141-97-9 ]
[ 1341220-17-4 ]

Yield	Reaction Conditions	Operation in experiment
65%	With thiourea S,S-dioxide at 80℃; for 8h;
48%	With piperidine In ethanol at 20℃; for 17h;
48%	With piperidine In ethanol at 20℃; for 17h;

Reference： [1]Location in patent: scheme or table Verma, Sanny; Kumar, Subodh; Jain, Suman L.; Sain, Bir [Organic and Biomolecular Chemistry, 2011, vol. 9, # 20, p. 6943 - 6948]
[2]Current Patent Assignee: DISCOVERYBIOMED INC - WO2014/152213, 2014, A2 Location in patent: Page/Page column 41
[3]Current Patent Assignee: DISCOVERYBIOMED INC - WO2014/152278, 2014, A2 Location in patent: Page/Page column 40

24
[ 1927-94-2 ]
[ 100-39-0 ]
[ 80352-52-9 ]

Yield	Reaction Conditions	Operation in experiment
95%	With potassium carbonate In acetonitrile for 4h; Reflux;	100 Preparation example 100 : 2-(benzyloxy)-3-chlorobenzaldehyde Preparation example 100 : 2-(benzyloxy)-3-chlorobenzaldehyde To a stirred solution of 3-chloro-2~hydroxybenzalclehyde(Preparat ion example 99, 16.5 g, 106.98 mmol) in acetonitrile (165mL) was added benzyl bromide (19.21g, 112.33mmol) and K2C03 (17.74g, 128.38mmol) at room temperature sequen ially. The mixture was heated to reflux then stirred for 4hr. The resulting mixture was cooled to room temperature, filtered through celite, and concentrated under reduced pressure. The crude compound was purified by a silica gel column to produce the title compound. (22.4g, 80~95 ) . NMR (400MHz, CDC13) δ 5.16 (s, 2H) . 7.18-7.23 (m, 1H) , 7.35-7 (m, 5H), 7.66-7.71 (m, 2H), 7.71-7.76 (m, 1H), 10.12 (d, /=0.8, 1H).
92%	With potassium carbonate In tetrahydrofuran at 20℃; for 47h; Inert atmosphere; Reflux;

Reference： [1]Current Patent Assignee: BIO-PHARM SOLUTIONS CO LTD - WO2015/88272, 2015, A1 Location in patent: Page/Page column 67-68
[2]Location in patent: experimental part Millan, David S.; Bunnage, Mark E.; Burrows, Jane L.; Butcher, Kenneth J.; Dodd, Peter G.; Evans, Timothy J.; Fairman, David A.; Hughes, Samantha J.; Kilty, Iain C.; Lemaitre, Arnaud; Lewthwaite, Russell A.; Mahnke, Axel; Mathias, John P.; Philip, James; Smith, Robert T.; Stefaniak, Mark H.; Yeadon, Michael; Phillips, Christopher [Journal of Medicinal Chemistry, 2011, vol. 54, # 22, p. 7797 - 7814]

25
[ 2960-66-9 ]
[ 552-16-9 ]
[ 1927-94-2 ]
8-chloro-3-formyl-2H-chromene-2-carboxylic acid ethyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
50.1%	With pyrrolidine In dimethyl sulfoxide at 25℃; for 78h;	20.1 Step 1(E)-4-Oxo-but-2-enoic acid ethyl ester (2.7 mL, 22.99 mmol), 2-nitro benzoic acid (0.648 g, 3.83 mmol), and pyrrolidine (0.31 mL, 3.83 mmol) were added simultaneously to a solution of commercially available 3-chloro-2-hydroxy-benzaldehyde (5.0 g, 19.16 mmol) in dimethysulfoxide (20 mL) at 25°C and the solution was stirred for 78 hours at 25°C. The reaction was quenched by the addition of water. The reaction mixture was then partitioned between water and ethyl acetate. The combined organics were washed with a saturated brine solution, dried over anhydrous sodium sulfate, filtered, rinsed and concentrated in vacuo. The residue obtained was purified on a silica gel Flash column chromatography using ethyl acetate- hexanes (1: 1.2) as eluents, yielded 5-chloro-3-formyl-2H-chromene-2-carboxylic acid ethyl ester as a solid (2.10 g, 50.1%).

Reference： [1]Current Patent Assignee: ROCHE HOLDING AG - WO2011/157682, 2011, A1 Location in patent: Page/Page column 71

26
[ 108-86-1 ]
[ 1927-94-2 ]
[ 1374329-50-6 ]

Yield	Reaction Conditions	Operation in experiment
85%	Stage #1: bromobenzene With iodine; magnesium In diethyl ether at 20℃; for 0.5h; Stage #2: 3-chlorosalicylaldehyde In tetrahydrofuran; diethyl ether at 0 - 20℃; for 14h;	Salicyl Alcohols 5a-i,k-w; General Procedure General procedure: Mg turnings (420 mg, 17.5 mmol) were placed in 25-mL round-bottom flask followed by the addition of several crystals of molecular I2. The flask was heated upon shaking until violet vapor appeared. The flask was cooled to rt, and Et2O (10 mL) was added. The organic bromide (17.5 mmol; for the synthesis of 5p-s MeI was used) was added dropwise to the resulting suspension of Mg turnings in Et2O over 30 min. The suspension was stirred until metallic Mg fully reacted with the organic halide, at which point it was transferred into a solution of salicyl aldehyde (7 mmol) in Et2O/THF (1:1, 30 mL) through a cannula at 0 °C. The resulting mixture was stirred for 2 h at this temperature and a further 12 h at r.t. Upon completion, the mixture was cooled to 0 °C, quenched with sat. NH4Cl (10 mL, portionwise addition), and diluted with water (100 mL). The organic phase was separated and the aqueous phase was extracted with EtOAc (2 × 20 mL). The combined organic fractions were washed with water (2 × 20 mL) and brine (2 ×10 mL), dried (anhyd Na2SO4), and concentrated. The oily residue was subjected to column chromatography (silica gel, gradient elution petroleum ether/EtOAc 50:1 to 10:1) to afford the target alcohol.
	Stage #1: bromobenzene With magnesium In diethyl ether for 1.5h; Reflux; Stage #2: 3-chlorosalicylaldehyde In diethyl ether at 0℃; for 2h; Reflux;

Reference： [1]Abaev, Vladimir T.; Chalikidi, Petrakis N.; Kekhvaeva, Anna E.; Makarov, Anton S.; Trushkov, Igor V.; Uchuskin, Maxim G. [Synthesis, 2019, vol. 51, # 19, p. 3747 - 3757]
[2]Sun, Huayin; Zhang, Yonghui; Guo, Fengfeng; Yan, Yizhe; Wan, Changfeng; Zha, Zhenggen; Wang, Zhiyong [European Journal of Organic Chemistry, 2012, # 3, p. 480 - 483]

27
[ 50-00-0 ]
[ 1927-94-2 ]
[ 107-15-3 ]
[ 1336921-72-2 ]

Yield	Reaction Conditions	Operation in experiment
78%	Stage #1: 3-chlorosalicylaldehyde; ethylenediamine In methanol at 20℃; for 3h; Stage #2: With sodium tetrahydroborate In methanol Stage #3: formaldehyd With sodium tetrahydroborate In acetonirtrile; water; acetic acid	To a stirred solution of 3-chloro-2-hydroxybenzaldehyde (1.00 gr, 6.4 mmol) in 10 mL of methanol was slowly added a solution of ethylenediamine (0.22 mL, 3.2 mmol) in 30 mL methanol. The solution was stirred for 3 hours at room temperature forming a yellow solution. Sodium borohydride (1.51 gr, 40 mmol) was added in small portions, and the reaction was stirred overnight. The solution became colorless and a white solid precipitated. 100 mL of water were added, and the white precipitate formed was collected by vacuum filtration (0.98 gr, 45%). To a solution of this product (0.98 gr, 2.9 mmol) in acetonitrile (110 mL) and acetic acid (15 mL) was added formaldehyde (5.5 mL, 69.4 mmol, 37% in water), and the mixture was stirred for 45 min. NaBHU was added (1.51 gr, 40 mmol) and the reaction was stirred for 12 h. Acetonitrile was removed in vacuum. The residue was hydrolyzed with 50 mL 2M NaOH, leading to a precipitation of white solid. The precipitate was collected by vacuum filtration and was washed with methanol (0.83 gr, 78%).

Reference： [1]Current Patent Assignee: Yissum Research & Development (in: Hebrew University); HEBREW UNIVERSITY OF JERUSALEM - WO2012/7948, 2012, A2 Location in patent: Page/Page column 38-39

28
[ 1927-94-2 ]
[ 403-42-9 ]
[ 1377689-50-3 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 20℃; for 5h;	4.2. General synthetic procedure of chalcones (1a-1t) General procedure: Equimolar portions of the appropriately substituted salicylaldehydes (2 mmol, 1 equiv) and substituted acetophenone (2 mmol, 1 equiv) were dissolved in approximately 20 mL of ethanol. The mixture was allowed to stir for several minutes at 0 °C to let dissolve. Then, a 0.5 mL aliquot of a 40% aqueous sodium hydroxide solution was slowly added dropwise to the reaction flask via a self-equalizing addition funnel. The reaction solution was allowed to stir at room temperature for approximately 4-6 h. The mixture was adjusted to pH 5.0 with dilute hydrochloric acid until the reaction was complete. The reaction was monitored by TLC. Most commonly, a precipitate formed and was then collected by suction filtration.

Reference： [1]Location in patent: experimental part Zhang, Hui; Liu, Jia-Jia; Sun, Jian; Yang, Xian-Hui; Zhao, Ting-Ting; Lu, Xiang; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3212 - 3218]

29
[ 1927-94-2 ]
[ 99-91-2 ]
[ 1377689-62-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 20℃; for 5h;	4.2. General synthetic procedure of chalcones (1a-1t) General procedure: Equimolar portions of the appropriately substituted salicylaldehydes (2 mmol, 1 equiv) and substituted acetophenone (2 mmol, 1 equiv) were dissolved in approximately 20 mL of ethanol. The mixture was allowed to stir for several minutes at 0 °C to let dissolve. Then, a 0.5 mL aliquot of a 40% aqueous sodium hydroxide solution was slowly added dropwise to the reaction flask via a self-equalizing addition funnel. The reaction solution was allowed to stir at room temperature for approximately 4-6 h. The mixture was adjusted to pH 5.0 with dilute hydrochloric acid until the reaction was complete. The reaction was monitored by TLC. Most commonly, a precipitate formed and was then collected by suction filtration.

Reference： [1]Location in patent: experimental part Zhang, Hui; Liu, Jia-Jia; Sun, Jian; Yang, Xian-Hui; Zhao, Ting-Ting; Lu, Xiang; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3212 - 3218]

30
[ 1927-94-2 ]
[ 99-90-1 ]
[ 1377689-74-1 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 20℃; for 5h;	4.2. General synthetic procedure of chalcones (1a-1t) General procedure: Equimolar portions of the appropriately substituted salicylaldehydes (2 mmol, 1 equiv) and substituted acetophenone (2 mmol, 1 equiv) were dissolved in approximately 20 mL of ethanol. The mixture was allowed to stir for several minutes at 0 °C to let dissolve. Then, a 0.5 mL aliquot of a 40% aqueous sodium hydroxide solution was slowly added dropwise to the reaction flask via a self-equalizing addition funnel. The reaction solution was allowed to stir at room temperature for approximately 4-6 h. The mixture was adjusted to pH 5.0 with dilute hydrochloric acid until the reaction was complete. The reaction was monitored by TLC. Most commonly, a precipitate formed and was then collected by suction filtration.

Reference： [1]Location in patent: experimental part Zhang, Hui; Liu, Jia-Jia; Sun, Jian; Yang, Xian-Hui; Zhao, Ting-Ting; Lu, Xiang; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3212 - 3218]

31
[ 1927-94-2 ]
[ 122-00-9 ]
[ 1377689-27-4 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 20℃; for 5h;	4.2. General synthetic procedure of chalcones (1a-1t) General procedure: Equimolar portions of the appropriately substituted salicylaldehydes (2 mmol, 1 equiv) and substituted acetophenone (2 mmol, 1 equiv) were dissolved in approximately 20 mL of ethanol. The mixture was allowed to stir for several minutes at 0 °C to let dissolve. Then, a 0.5 mL aliquot of a 40% aqueous sodium hydroxide solution was slowly added dropwise to the reaction flask via a self-equalizing addition funnel. The reaction solution was allowed to stir at room temperature for approximately 4-6 h. The mixture was adjusted to pH 5.0 with dilute hydrochloric acid until the reaction was complete. The reaction was monitored by TLC. Most commonly, a precipitate formed and was then collected by suction filtration.

Reference： [1]Location in patent: experimental part Zhang, Hui; Liu, Jia-Jia; Sun, Jian; Yang, Xian-Hui; Zhao, Ting-Ting; Lu, Xiang; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3212 - 3218]

32
[ 1927-94-2 ]
[ 100-06-1 ]
[ 1377689-38-7 ]

Yield	Reaction Conditions	Operation in experiment
	With sodium hydroxide In ethanol; water at 20℃; for 5h;	4.2. General synthetic procedure of chalcones (1a-1t) General procedure: Equimolar portions of the appropriately substituted salicylaldehydes (2 mmol, 1 equiv) and substituted acetophenone (2 mmol, 1 equiv) were dissolved in approximately 20 mL of ethanol. The mixture was allowed to stir for several minutes at 0 °C to let dissolve. Then, a 0.5 mL aliquot of a 40% aqueous sodium hydroxide solution was slowly added dropwise to the reaction flask via a self-equalizing addition funnel. The reaction solution was allowed to stir at room temperature for approximately 4-6 h. The mixture was adjusted to pH 5.0 with dilute hydrochloric acid until the reaction was complete. The reaction was monitored by TLC. Most commonly, a precipitate formed and was then collected by suction filtration.

Reference： [1]Location in patent: experimental part Zhang, Hui; Liu, Jia-Jia; Sun, Jian; Yang, Xian-Hui; Zhao, Ting-Ting; Lu, Xiang; Gong, Hai-Bin; Zhu, Hai-Liang [Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 10, p. 3212 - 3218]

33
[ 1927-94-2 ]
[ 1383730-50-4 ]
[ 1383730-71-9 ]

Yield	Reaction Conditions	Operation in experiment
76%	With sodium carbonate In methanol; water Reflux;	4.4. General procedure for the synthesis of chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35 General procedure: To a stirred solution of isoquinolinium salt (1 mmol) 1-5 and aldehyde (0.9 mmol) in a mixture of of methanol (A mL) and water (B mL), solid Na2CO3 (0.2 mmol) was added at reflux. The reaction mixture was heated at reflux for 1-2 h (TLC monitoring). After cooling, the precipitate was filtered-off, washed with water (3x) and with methanol once to give the target chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35.

Reference： [1]Location in patent: experimental part Voskressensky, Leonid G.; Festa, Alexey A.; Sokolova, Ekaterina A.; Varlamov, Alexey V. [Tetrahedron, 2012, vol. 68, # 27-28, p. 5498 - 5504]

34
[ 1927-94-2 ]
[ 1383730-51-5 ]
[ 1383730-78-6 ]

Yield	Reaction Conditions	Operation in experiment
41%	With sodium carbonate In methanol; water Reflux;	4.4. General procedure for the synthesis of chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35 General procedure: To a stirred solution of isoquinolinium salt (1 mmol) 1-5 and aldehyde (0.9 mmol) in a mixture of of methanol (A mL) and water (B mL), solid Na2CO3 (0.2 mmol) was added at reflux. The reaction mixture was heated at reflux for 1-2 h (TLC monitoring). After cooling, the precipitate was filtered-off, washed with water (3x) and with methanol once to give the target chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35.

Reference： [1]Location in patent: experimental part Voskressensky, Leonid G.; Festa, Alexey A.; Sokolova, Ekaterina A.; Varlamov, Alexey V. [Tetrahedron, 2012, vol. 68, # 27-28, p. 5498 - 5504]

35
[ 1927-94-2 ]
[ 1383730-49-1 ]
[ 1383730-63-9 ]

Yield	Reaction Conditions	Operation in experiment
52%	With sodium carbonate In methanol; water Reflux;	4.4. General procedure for the synthesis of chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35 General procedure: To a stirred solution of isoquinolinium salt (1 mmol) 1-5 and aldehyde (0.9 mmol) in a mixture of of methanol (A mL) and water (B mL), solid Na2CO3 (0.2 mmol) was added at reflux. The reaction mixture was heated at reflux for 1-2 h (TLC monitoring). After cooling, the precipitate was filtered-off, washed with water (3x) and with methanol once to give the target chromeno[2',3':4,5]imidazo[2,1-a]isoquinolines 7-35.

Reference： [1]Location in patent: experimental part Voskressensky, Leonid G.; Festa, Alexey A.; Sokolova, Ekaterina A.; Varlamov, Alexey V. [Tetrahedron, 2012, vol. 68, # 27-28, p. 5498 - 5504]

36
[ 1927-94-2 ]
[ 536-74-3 ]
C₁₅H₁₁ClO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: ethynylbenzene With n-butyllithium In tetrahydrofuran at -78 - -40℃; for 6h; Inert atmosphere; Stage #2: 3-chloro-2-hydroxybenzaldehyde In tetrahydrofuran at -78℃; for 2h; Inert atmosphere;
	Stage #1: ethynylbenzene With n-butyllithium In tetrahydrofuran at -78℃; for 1h; Inert atmosphere; Stage #2: 3-chloro-2-hydroxybenzaldehyde In tetrahydrofuran at -40℃; for 2h; Inert atmosphere;

Reference： [1]Zhang, Shuai; Wan, Changfeng; Wang, Qiang; Zhang, Baiqun; Gao, Lingfeng; Zha, Zhenggen; Wang, Zhiyong [European Journal of Organic Chemistry, 2013, # 11, p. 2080 - 2083]
[2]Chaudhary, Chhabi Lal; Hyun, Soonsil; Jung, Chanhyun; Jung, Jae-Kyung; Kang, Young Kee; Lee, Heesoon; Lee, Kiho; Lee, Kwanghee; Li, Siyuan; Viji, Mayavan [Green Chemistry, 2022, vol. 24, # 6, p. 2376 - 2384]

37
[ 1927-94-2 ]
[ 112245-13-3 ]
(S)-2-(N-3'-chlorosalicylidene)-amino-3,3-dimethyl-1-butanol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With sodium sulfate In ethanol for 16h; Reflux; Enzymatic reaction;	1 Experimental procedure for Schiff base ligand synthesis. (S)-2-(N-3'-Chlorosalicylidene)-amino-3,3-dimethyl-1-butanol (7) General procedure: Commercially available salicylaldehyde (1mmol) and sodium sulfate (0.5g) were added to a solution of (S)-tert-leucinol (1mmol) or l-valinol (1mmol) in ethanol (20mL). The reaction mixture was stirred under reflux for 16h, filtered and concentrated under reduced pressure. The reaction mixture was then dissolved in dichloromethane (10mL) and washed with water (3×10mL) and brine (15mL). The organic layer was dried and concentrated under reduced pressure to leave the crude product, which was purified by column chromatography on silica gel (8:2 hexane/ethyl acetate) to yield the pure ligand. (S)-2-(N-3'-Chlorosalicylidene)-amino-3,3-dimethyl-1-butanol (7) Yellow solid, 75%; mp 93-95 °C; 1H NMR δH (300 MHz) 1.01 (9H, s), 1.62 (1H, br s), 2.83 (1H, br s), 3.05 (1H, dd, J 3.0 Hz and 9.5 Hz), 3.72 (1H, overlapping dd, J 11.1 Hz and 9.6 Hz), 3.99 (1H, dd, J 11.1 Hz and 2.4 Hz), 6.64 (1H, dd, appears as t, J 7.8 Hz and 7.8 Hz), 7.13 (1H, dd, J 7.7 Hz and 1.8 Hz), 7.33 (1H, dd, J 7.8 Hz and 1.8 Hz), 8.25 (1H, s); 13C NMR δC (75.5 MHz) 26.9, 33.1, 62.0, 79.5, 117.3, 118.1, 122.7, 130.4, 133.3, 160.9, 165.6; (found: C, 60.80; H, 7.04; N, 5.38). C13H1835ClNO2 requires C, 61.05; H, 7.09; N, 5.48); =-60.8 (c 1.0, CHCl3).

Reference： [1]O'Mahony, Graham E.; Eccles, Kevin S.; Morrison, Robin E.; Ford, Alan; Lawrence, Simon E.; Maguire, Anita R. [Tetrahedron, 2013, vol. 69, # 47, p. 10168 - 10184]

38
[ 1927-94-2 ]
[ 1449600-81-0 ]

Yield	Reaction Conditions	Operation in experiment
86%	With sulphamoyl chloride In N,N-dimethyl acetamide at 0 - 20℃; for 12h; Inert atmosphere; Schlenk technique;
85%	With sulphamoyl chloride In N,N-dimethyl acetamide at 0 - 20℃; for 18h; Inert atmosphere;
	With sulphamoyl chloride In N,N-dimethyl acetamide at 20℃; for 18h;

	With dmap; formic acid; isocyanate de chlorosulfonyle at 0 - 25℃; for 18h; Inert atmosphere;
	With sulphamoyl chloride In N,N-dimethyl acetamide for 18h; Inert atmosphere;
	With sulphamoyl chloride In N,N-dimethyl acetamide at 0 - 20℃; for 18h; Inert atmosphere;
	With sulphamoyl chloride In N,N-dimethyl acetamide at 0 - 20℃; for 12h;	General procedure: To a solution of salicylaldehyde (15.0 mmol) in DMA (100 mL) at0 C was carefully added freshly prepared ClSO2NH2 (4.6 g,40.0 mmol) in small portions, and the resulting solutionwas stirredfor 12 h at room temperature. The reaction was quenched carefullywith ice-cold water (100 mL), and the mixture was transferred to aseparating funnel containing CH2Cl2 (200 mL). The aqueous layerwas separated and extracted with CH2Cl2 (3 50 mL), and thecombined organic layers were washed with saturated NaHCO3 solution(100 mL), dried (MgSO4), filtered through a short pad of silicausing CH2Cl2 as eluent and concentrated in vacuo. Imino sulfonates5 were isolated by flash chromatography (PE/EtOAc) on silica gel.

Reference： [1]Spielmann, Kim; Lee, Arie Van Der; De Figueiredo, Renata Marcia; Campagne, Jean-Marc [Organic Letters, 2018, vol. 20, # 5, p. 1444 - 1447]
[2]Ahn, Hye-In; Cho, Ho-Jun; Kim, Ju Hyun; Park, Jong-Un; Xuan, Zi [Advanced synthesis and catalysis, 2020]
[3]Yang, Zhilin; Yu, Hao; Zhang, Lei; Wei, Hang; Xiao, Yumei; Chen, Lanzhen; Guo, Hongchao [Chemistry - An Asian Journal, 2014, vol. 9, # 1, p. 313 - 318]
[4]Mao, Biming; Shi, Wangyu; Liao, Jianning; Liu, Honglei; Zhang, Cheng; Guo, Hongchao [Organic Letters, 2017, vol. 19, # 23, p. 6340 - 6343]
[5]Wang, Chang; Li, Yan; Wu, Yang; Wang, Qijun; Shi, Wangyu; Yuan, Chunhao; Zhou, Leijie; Xiao, Yumei; Guo, Hongchao [Organic Letters, 2018, vol. 20, # 10, p. 2880 - 2883]
[6]Shi, Wangyu; Zhou, Leijie; Mao, Biming; Wang, Qijun; Wang, Chang; Zhang, Cheng; Li, Xuefeng; Xiao, Yumei; Guo, Hongchao [Journal of Organic Chemistry, 2019, vol. 84, # 2, p. 679 - 685]
[7]Wei, Bo; Zhou, Jing; Xu, Jia-Jia; Cui, Jing; Ping, Feng-Feng; Ling, Jing-Jing; Chen, Ya-Jing [European Journal of Medicinal Chemistry, 2019, vol. 184]

39
[ 1927-94-2 ]
[ 63-74-1 ]
[ 84907-36-8 ]

Yield	Reaction Conditions	Operation in experiment
85%	With formic acid In methanol Reflux;
	In ethanol for 6h; Reflux;

Reference： [1]Akocak, Suleyman; AlOthman, Zeid; Demir, Yeliz; Durgun, Mustafa; Kuru, Ali; Osman, Sameh M.; Supuran, Claudiu T.; Beydemir, Şükrü; Güzel, Abdussamat; Işık, Mesut; Saklı, Ali; Türkeş, Cüneyt [Journal of Enzyme Inhibition and Medicinal Chemistry, 2020, vol. 35, # 1, p. 950 - 962]
[2]Luci, Diane K.; Jameson, J. Brian; Yasgar, Adam; Diaz, Giovanni; Joshi, Netra; Kantz, Auric; Markham, Kate; Perry, Steve; Kuhn, Norine; Yeung, Jennifer; Kerns, Edward H.; Schultz, Lena; Holinstat, Michael; Nadler, Jerry L.; Taylor-Fishwick, David A.; Jadhav, Ajit; Simeonov, Anton; Holman, Theodore R.; Maloney, David J. [Journal of Medicinal Chemistry, 2014, vol. 57, # 2, p. 495 - 506]

40
[ 3731-51-9 ]
[ 1927-94-2 ]
[ 1542929-38-3 ]

Yield	Reaction Conditions	Operation in experiment
94%	In methanol at 29.84℃; for 3h;	2.1. Synthesis and crystallization For the preparation of ligand L1, 2-picolylamine (0.54 g,5 mmol) was added to a solution of 3-chloro-2-hydroxybenzaldehyde (0.785 g, 5 mmol) in methanol (30 ml) and the resulting solution stirred at 303 K for 3 h. A brown oil was obtained after evaporation. The pure ligand was obtained as a yellow powder by recrystallization from a solution in chloroform-hexane (1:6 v/v) (yield 1.16 g, 94%).

Reference： [1]Kim, Young-Inn; Lee, Jin Young; Song, Young-Kwang; Kang, Sung Kwon [Acta Crystallographica, Section C: Crystal Structure Communications, 2013, vol. 69, # 11, p. 1348 - 1350]

41
[ 1927-94-2 ]
[ 19652-33-6 ]

Yield	Reaction Conditions	Operation in experiment
	With N-Bromosuccinimide at 20℃; for 2h;	1 Synthesis of 5-bromo-3-chloro-2-hydroxybenzaldehyde (2) Synthesis of 5-bromo-3-chloro-2-hydroxybenzaldehyde (2): 3-Chloro-2- hydroxybenzaldehyde (1) (10 g, 63.87 mmol) was dissolved in PEG-400 (50 mL) at room temperature. N-Bromosuccinimide (11.94 g, 67.06 mmol) was added to the reaction mixture and stirred for 2 h. The reaction mixture was transferred into iced water and extracted with ethyl acetate (3 x 500 mL). The combined organic layers were washed with brine and dried over anhydrous Na2S04. The organic layer was concentrated under reduced pressure to give 5-bromo-3-chloro-2-hydroxybenzaldehyde (2), which was used in the next step without further purification. 1H MR (400 MHz, DMSO-c δ 11.22 (s, 1H), 10.12 (s, 1H), 8.00 (s, 1H), 7.84 (s, 1H).

Reference： [1]Current Patent Assignee: KARYOPHARM THERAPEUTICS INC - WO2015/3166, 2015, A1 Location in patent: Paragraph 00360

42
[ 123-91-1 ]
[ 1927-94-2 ]
2-(1,4-dioxan-2-yloxy)-3-chlorobenzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
42%	With tert.-butylhydroperoxide; copper(l) chloride In water at 100℃;	10 General procedure for the synthesis of acetals, preparation of 3a as representative example General procedure: To a flask charged with a stir bar, 1a (25.0 mg, 0.20 mmol, 1.0 equiv), CuCl (1.0 mg, 0.01 mmol, 0.05 equiv), TBHP (0.059 mL, 0.61 mmol, 70 wt % in water, 3.0 equiv), and 1,4-dioxane as ether (2.0 mL, 22.8 mmol, 112.0 equiv) were mixed at room temperature. The reaction temperature was increased to 100°C and the reaction mixture was stirred for 15-90 min. The reaction mixture was cooled to room temperature and the solvent was removed under vacuum yielding the crude product, which was purified by flash chromatography (ethyl acetate/hexane, 2:8) to afford the required product 3a.

Reference： [1]Barve, Balaji D.; Wu, Yang-Chang; El-Shazly, Mohamed; Korinek, Michal; Cheng, Yuan-Bin; Wang, Jeh-Jeng; Chang, Fang-Rong [Tetrahedron, 2015, vol. 71, # 15, p. 2290 - 2297]

43
[ 1927-94-2 ]
3-ethyl-1-isopentyl-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride [ No CAS ]
8-[(3-chloro-2-hydroxyphenyl)methyl]-3-ethyl-1-(3-methylbutyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
43%	Stage #1: 3-chlorosalicylaldehyde; 3-ethyl-1-isopentyl-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride In N,N-dimethyl-formamide at 20℃; for 0.5h; Stage #2: With sodium tris(acetoxy)borohydride In N,N-dimethyl-formamide at 20℃; for 24h; Stage #3: With hydrogenchloride In 1,4-dioxane; diethyl ether	8-[(3-chloro-2-hydroxyphenyl)methyl]-3-ethyl-1-(3-methylbutyl)-1,3,8-triazaspiro[4.5]decane-2,4-dione hydrochloride (12i) A mixture of 12n (0.15 mmol) and 3-chloro-2-hydroxybenzaldehyde (0.20 mmol) was dissolved in DMF (2 mL) and was stirred at room temp for 30 minutes before the addition of sodium triacetoxyborohydride (0.20 mmol). The reaction stirred under positive nitrogen pressure at room temp for 24h. The mixture was the quenched with water, dissolved in water/brine, and extracted with DCM washes. The crude was then dissolved into ether and purified by HCl salt formation with 4M HCl in dioxane. Clear resin, HCl salt, 40mg, 0.0877 mmol, 43% yield, >94% HPLC purity, ES-MS m/z 408 (M+H). 1HNMR (400 MHz, DMSO-d6) δ 9.98 - 10.23 (m, 1 H), 7.55 (d, J=7.8 Hz, 2 H), 7.02 (t, J=7.8 Hz,1 H), 4.43 (br. s., 2 H), 3.49 (br. s., 4 H), 3.42-3.46 (m, 2 H), 3.13-3.30 (m, 2 H), 2.50 (d, J=1.7Hz, 2 H), 2.00 (d, J=14.2 Hz, 2 H), 1.60 (s, 1 H), 1.40-1.53 (m, 2 H), 1.05-1.18 (m, 3 H), 0.90 -1.02 (m, 6 H).

Reference： [1]Meyers, Marvin J.; Anderson, Elizabeth J.; McNitt, Sarah A.; Krenning, Thomas M.; Singh, Megh; Xu, Jing; Zeng, Wentian; Qin, Limei; Xu, Wanwan; Zhao, Siting; Qin, Li; Eickhoff, Christopher S.; Oliva, Jonathan; Campbell, Mary A.; Arnett, Stacy D.; Prinsen, Michael J.; Griggs, David W.; Ruminski, Peter G.; Goldberg, Daniel E.; Ding, Ke; Liu, Xiaorong; Tu, Zhengchao; Tortorella, Micky D.; Sverdrup, Francis M.; Chen, Xiaoping [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 16, p. 5144 - 5150]

44
[ 1569-60-4 ]
[ 1927-94-2 ]
C₁₅H₁₉ClO₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With tetrafluoroboric acid diethyl ether In dichloromethane at 0℃; for 4h; diastereoselective reaction;	General procedure for synthesis of pyrano(3,2-c)-chromene derivatives: General procedure: To a solution of 6-methylhept-5-en-2-ol (2.0 mmol, 2.0 equiv.) and sailcylaldehyde (1.0 mmol, 1.0 equiv.) in dryCH2Cl2 (2 mL) was added slowly HBF4.OEt2 or TfOH (0.3 mmol, 0.3 equiv.) at 0 oC and thereaction mixture was allowed to stirr at 0 oC for 3-5 h. After completion of the reaction (asmonitored by TLC) saturated aq. NaHCO3 solution (10 mL)was added to the reaction mixtureand extracted with ethyl acetate (3x10 mL). The organic layer was washed with brine (1x10 mL)and dried over anhydrous sodium sulfate. The organic layer was concentrated under rotaryevaporator and column chromatographed on silica gel (100-200 mesh) using 1 : 99 ethyl acetate-hexane mixture as eluent to get pure pyrano(3,2-c)-chromene derivatives.

Reference： [1]Sarmah, Barnali; Baishya, Gakul; Hazarika, Nabajyoti; Das, Pranab Jyoti [Synlett, 2015, vol. 26, # 15, p. 2151 - 2155]

45
[ 95-57-8 ]
[ 100-97-0 ]
[ 2420-16-8 ]
[ 1927-94-2 ]
[ 3328-72-1 ]

Yield	Reaction Conditions	Operation in experiment
1: 21% 2: 34% 3: 5.8%	Stage #1: 2-monochlorophenol; hexamethylenetetramine With copper(I) oxide In trifluoroacetic acid for 5h; Reflux; Stage #2: With hydrogenchloride In water at 20℃; for 1h; regioselective reaction;	General procedure for the synthesis of target compounds General procedure: To a solution of substrates (1a-1q, 0.15 mmol) in trifluoroacetic acid (5 ml), hexamethylenetetramine (0.3 mmol) and cuprous oxide (0.15 mmol) were added. The reaction mixture was refluxed for about 5 h, cooled to room temperature, followed by addition of hydrochloric acid (3 N, 5 ml). After stirring for another 1 h, the solution was concentrated under reduced pressure. The products were purified by silica gel column chromatography (200-300 mesh).

Reference： [1]Fu, Xue-Wen; Pu, Wen-Chen; Zhang, Guo-Lin; Wang, Chun [Research on Chemical Intermediates, 2015, vol. 41, # 11, p. 8147 - 8158]

46
[ 1927-94-2 ]
[ 10242-10-1 ]

Reference： [1]Patent: WO2015/164482,2015,A1

47
[ 1927-94-2 ]
[ 108-24-7 ]
Acetic acid 2-chloro-6-diacetoxymethyl-phenyl ester [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With tungstate sulfuric acid In neat (no solvent) at 20℃; for 0.0666667h; Green chemistry;

Reference： [1]Kalla, Reddi Mohan Naidu; Kim, Mi Ri; Kim, Yu Na; Kim, Il [New Journal of Chemistry, 2016, vol. 40, # 1, p. 687 - 693]

48
[ 95-57-8 ]
[ 33513-42-7 ]
[ 1927-94-2 ]

Yield	Reaction Conditions	Operation in experiment
70%	Stage #1: N,N-dimethyl-formamide With trichlorophosphate In acetonitrile at -5℃; for 1h; Stage #2: 2-monochlorophenol With copper(II) nitrate In acetonitrile at 20℃; for 18h; Stage #3: With water In acetonitrile Heating;	Materials General procedure: Solvents such as acetonitrile and dichloroethane were of highest purity HPLC grade.Deionized water was further purified over acid dichromate and alkaline permanganatesolutions before use. All the other chemicals used in this study (organic substrates such ashydrocarbons, phenols, and their substituted compounds) were procured from SigmaAldrich Chemicals (Hyderabad, India) with highest purity (99 %). A carbonate-freesodium hydroxide stock solution was prepared according to standard procedures and theconcentration was systematically checked by titration against potassium hydrogen phthalate.All the metal nitrates used in the present work were of Analytical Reagent (AR) gradeof 99 % purity (S.D. Fine Chemicals Ltd., India). Stock solutions of metal nitrates (Cu(II),Co(II), Ni(II) and Cd(II) nitrates) were prepared in acetonitrile solvent and standardized byEDTA titrations according to literature procedures [33].2.2 VH Reagents Flasks containing DMF dissolved in a suitable solvent {generally dichloroethane (DCE), oracetonitrile (ACN)}, along with SOCl2 and POCl3, were cooled and thermally equilibratedfor about 30 min at -5 °C by keeping them in a benzene trough chilled from outside withice and NaCl. Requisite amounts of solvent and amide were transferred into a 100 mL flaskand POCl3 or SOCl2 was added drop wise, at -5 °C, with constant stirring. The resultantreagent mixture was kept aside for about an hour to ensure complete formation of the VHadduct. Its concentration was checked by acid-base titration to the bromocresol green endpoint according to literature reports [9-14]. 2.3 Kinetic MethodOrganic substrates such as hydrocarbons, phenols, and their substituted derivatives wereused for kinetic studies of VH reactions in ACN and DCE. The thermostat (Toshniwal,India) was adjusted to the desired reaction temperature (with a precision of ±0.1 °C). Twodifferent flasks, one containing known amount of Vilsmeier-Haack reagent (DMF/SOCl2or DMF/POCl3) in a suitable solvent, and the other with the substrate solution, were takenand clamped in the thermostatic bath for about 30 min. The reaction was initiated by adding the requisite amount of substrate solution to the reaction vessel containing the othercontents of the reaction mixture. The entire reaction mixture was stirred until the end of thereaction. A kinetic method was adopted to monitor progress of the VH reaction, which issimilar to that reported in our earlier papers [11-14]. Aliquots of the reaction mixture werewithdrawn into a conical flask, containing considerable (and known) amount of hot distilledwater, at different time intervals. The unreacted VH adduct underwent hydrolysis andgave a mixture of acids (hydrochloric and sulfuric acids for DMF/SOCl2 and hydrochloricand phosphoric acids for DMF/POCl3). The acid content was estimated against standardNaOH solution to the bromocresol green end point. Reproducibility of the results wascrosschecked by conducting kinetic runs three to four times. The results were reproduciblewithin ±3 % error. 2.4 Product Analysis Under Kinetic ConditionsAfter completing the kinetic study of the reaction, excess (remaining part of the reactionmixture) was refluxed further and left aside overnight. The solution was then poured into icecoldwater with vigorous stirring and kept aside for about 2 h. The resultant solution wasneutralized with sodium hydrogen carbonate. The organic phase was extracted with DCE, dried over MgSO4 and the solvent evaporated. Products of the reaction were isolated andfound to be formyl derivatives of the substrates (Scheme 1) as characterized by 1H-NMR andmass spectra with comparison to authentic samples and found to be satisfactory (Table 1).

Reference： [1]Rajanna; Ferdose, Aneesa; Rajendar Reddy; Arifuddin; Moazzam Ali [Journal of Solution Chemistry, 2016, vol. 45, # 3, p. 371 - 394]

49
[ 1927-94-2 ]
[ 22471-02-9 ]

Yield	Reaction Conditions	Operation in experiment
97%	Stage #1: 3-chloro-2-hydroxybenzaldehyde With 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; C₆H₁₃ClO₂Si; triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere; Stage #2: With N,N,N-tributylbutan-1-aminium fluoride In tetrahydrofuran; dichloromethane Inert atmosphere;
	With sodium tetrahydridoborate In ethanol at 0 - 20℃; for 2h;
	With sodium tetrahydridoborate; ethanol at 0 - 20℃; for 2h;

	With sodium tetrahydridoborate In ethanol at 0 - 20℃; for 2h;
	With sodium tetrahydridoborate In ethanol at 0 - 20℃; for 2h; Inert atmosphere;

Reference： [1]Assoah, Benedicta; Vale, João R.; Kalenius, Elina; Veiros, Luis F.; Candeias, Nuno R. [European Journal of Organic Chemistry, 2018, vol. 2018, # 23, p. 2910 - 2917]
[2]Delogu, Giovanna L.; Matos, Maria J.; Fanti, Maura; Era, Benedetta; Medda, Rosaria; Pieroni, Enrico; Fais, Antonella; Kumar, Amit; Pintus, Francesca [Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 9, p. 2308 - 2313]
[3]Fais, Antonella; Kumar, Amit; Medda, Rosaria; Pintus, Francesca; Delogu, Francesco; Matos, Maria J.; Era, Benedetta; Delogu, Giovanna L. [Bioorganic Chemistry, 2019, vol. 84, p. 302 - 308]
[4]Delogu, Giovanna Lucia; Era, Benedetta; Floris, Sonia; Medda, Rosaria; Sogos, Valeria; Pintus, Francesca; Gatto, Gianluca; Kumar, Amit; Westermark, Gunilla Torstensdotter; Fais, Antonella [International Journal of Biological Macromolecules, 2021, vol. 169, p. 428 - 435]
[5]Delogu, Giovanna L.; Era, Benedetta; Fais, Antonella; Goyal, Chinmayi; Kumar, Amit; Matos, Maria J.; Pintus, Francesca [Pharmaceuticals, 2022, vol. 15, # 3]

50
[ 1927-94-2 ]
[ 371-14-2 ]
C₁₃H₁₀ClFN₂O [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	With acetic acid In ethanol at 20℃; for 8h;	3.1.3. General Procedure for the Preparation of M2 General procedure: To a solution of aryl-aldehydes (5.0 mmol) and the corresponding phenylhydrazines (5.0 mmol)in ethanol (25 mL), was added one drop of acetic acid. The reaction mixture was stirred at roomtemperature for 8 h. After removing of the solvent, the residue was dissolved in CH2Cl2 (DCM) (20 mL),washed by water (10 mL), dried over Na2SO4, filtered and concentrated to give the hydrazones M2that were used without further purification.

Reference： [1]Liu, Guan-Nan; Luo, Rong-Hua; Zhou, Yu; Zhang, Xing-Jie; Li, Jian; Yang, Liu-Meng; Zheng, Yong-Tang; Liu, Hong [Molecules, 2016, vol. 21, # 9]

51
[ 553-53-7 ]
[ 1927-94-2 ]
N′-(3-chloro-2-hydroxy-phenylmethylidene)-3-pyridinecarbohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
78%	With acetic acid In ethanol for 1h; Reflux;
	In ethanol at 85℃; for 20h; Inert atmosphere;	2.1 Reagents General procedure: Aroylhydrazones 1-12 were prepared by mixing equimolar amounts of nicotinic acidhydrazide (Fluka) with the corresponding aldehyde or ketone (Sigma). The reactionswere carried out in dry ethanol under argon atmosphere at 85 C for 20 h. The solventwas evaporated and the solids were suspended in CH2Cl2, filtered (G-3), rinsed withCH2Cl2 (EtOH was used for 4, 5, 11 and 12), and dryed at 50 C over 24 h. Thehydrazones were characterized by standard analytical procedures (NMR, IR, MS, andHPLC).
	In ethanol at 85℃; for 20h; Inert atmosphere;	2.1. Reagents General procedure: Compounds 1-4 were prepared according to previously reportedmethod [27], by mixing equimolar amounts of nicotinic acidhydrazide (Fluka) with aldehyde (2,3-dihydroxybenzaldehyde, 2,5-dihydroxybenzaldehyde, 2-hydroxy-3-chlorobenzaldehyde and 2-hydroxy-4-methoxybenzaldehyde purchased from Sigma). The reactionswere carried out in dry ethanol under argon atmosphere at 85 °C for20 h. The solventwere evaporated fromreaction mixtures and the solidswere suspended in CH2Cl2 (EtOH was used for 2), filtered and dried at50 °C for 24 h. Hydrazones were characterized by standard analyticalmethods [27]. Deionized water and organic solvents of p.a. puritygrade (Kemika) were used for spectroscopic measurements.

In ethanol at 85℃; for 20h; Inert atmosphere;

2.3. Preparation of the ligands and metal complexes General procedure: Ligands H2L1-H2L5 were prepared according to the previouslydescribed procedure [42,43], by mixing equimolar amounts ofnicotinic acid hydrazide with the respective aldehyde. The reactionswere carried out in dry ethanol under argon atmosphere at85 °C for 20 h. The solvent was evaporated from reaction mixturesand the solids were suspended in CH2Cl2 (EtOH was used for H2L2),filtered and dried at 50 °C for 24 h. All copper(II) complexes wereprepared in a similar way: by addition of the methanolic solutioncontaining stoichiometric amount of the metal salt, CuCl2 x 2H2O(0.07 g in 10 mL), to the methanolic solution of the correspondingamount of ligand (0.10 or 0.20 g in 10 mL), under magnetic stirring,resulting in the reaction mixture with aroylhydrazone/Cu(II) molarratio of 1/1 or 2/1. The prepared complexes were passed through G4filter, washed out with the methanol solution and dried in anelectric dryer for 4 h at 80 °C.

Reference： [1]Braidy, Nady; Egan, Suhelen; Huang, Michael L. H.; Palanimuthu, Duraippandi; Richardson, Des R.; Salikin, Nor Hawani; Wu, Zhixuan [British Journal of Pharmacology, 2020]
[2]Benković; Kontrec; Tomišić; Budimir; Galić [Journal of Solution Chemistry, 2016, vol. 45, # 8, p. 1227 - 1245]
[3]Benković; Kenđel; Parlov-Vuković; Kontrec; Chiş; Miljanić; Galić [Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2018, vol. 190, p. 259 - 267]
[4]Kenđel, Adriana; Miljanić, Snežana; Kontrec, Darko; Soldin, Željka; Galić, Nives [Journal of Molecular Structure, 2020, vol. 1207]

52
[ 1927-94-2 ]
[ 79-11-8 ]
[ 24589-85-3 ]

Yield	Reaction Conditions	Operation in experiment
45%	With sodium hydroxide In water at 80℃; for 5h;	4 Preparation of 2-(2-Chloro-6-formylphenoxy)acetic acid (3) [00127] To a solution of 3-chloro-2-hydroxybenzaldehyde 1 (500 mg, 3.19 mmol) in water (6 mL) was added sodium hydroxide (255 mg, 6.38 mmol) followed by 2-chloroacetic acid 2 (301 mg, 3.19 mmol). The reaction mixture was heated to 80 °C for 5 h, at which time TLC analysis showed completion of reaction. The reaction mixture was acidified with 1M HC1 and extracted with ethyl acetate (3 X 15 mL). The combined fractions were dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by combiflash eluting with 20-25% ethyl acetate in hexane to afford 310 mg (45% yield) of the title compound 3 as a yellow solid. MS (ES+): mlz = 213.95 [M+Hjt

Reference： [1]Current Patent Assignee: UNIVERSITY OF MIAMI - WO2016/154255, 2016, A1 Location in patent: Paragraph 00127

53
[ 141-84-4 ]
[ 1927-94-2 ]
C₁₀H₆ClNO₂S₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
22%	With ammonium acetate In toluene at 120℃; for 2h; Microwave irradiation;	12 Example 12: Synthetic scheme for target NADi-136 [00151] To a solution of 2-hydroxy-3-chlorobenzaldehyde 1 (118 g, 0.75 mmol) in toluene was added 2-thioxothiazolidin-4-one 2 (100 mg, 0.75 mmol) followed by ammonium acetate (116 mg, 1.5 mmol). The reaction mixture was heated in microwave at 120 °C for 2 h. TLC showed the completion of reaction. Water was added and the product was extracted with EtOAc (30 mL x 2). The combined organic fractions were washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo to afford 45 mg (22% yield) of the title compound NADi-136 as a yellow solid. MS (ES+): mlz = 270.00 [M-1j ‘H NMR (400 MHz, DMSO-d6) = 1H NMR (400 MHz, DMSO-d6) ppm 13.81 (brs, 1H), 10.41 (brs, 1H) 7.83 (s, 1H) 7.52 (d, 1=7.72 Hz, 1H) 7.31 (d, 1=7.94 Hz, 1H) 7.03 (t, 1=8 Hz, 1H).

Reference： [1]Current Patent Assignee: UNIVERSITY OF MIAMI - WO2016/154255, 2016, A1 Location in patent: Paragraph 00151

54
[ 1927-94-2 ]
[ 78-95-5 ]
1-(7-chlorobenzofuran-2-yl)ethan-1-one [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
72%	With potassium carbonate In acetone at 20 - 80℃; for 4h; Inert atmosphere; Enzymatic reaction;	62 ]-(7-chlorobenzofuran-2-yl) ethan-] -one: To a stirred solution of 3-chloro-2- hydroxybenzaldehyde (6 g, 38 mmol) in acetone (80 mL) at room temperature under an argon atmosphere were added potassium carbonate (8 g, 58 mmol) and 1-chloropropan-2-one (4.4 g, 46 mmol). The reaction mixture was stirred at 80 °C for 4 h. After consumption of starting material (monitored by TLC), the reaction mixture was filtered, and the filtrate was concentrated in vacuo. The crude material was purified by column chromatography using 2- 5% EtOAc: Hexane to afford 1-(7-chlorobenzofuran-2-yl) ethan-1-one (5.4 g, 72%) as an off- white solid.[0425] ‘H NMR (CDC13: 400 MHz): 7.61 (dd, 1H), 7.52 (s, 1H), 7.48 (dd, 1H), 7.27 (t, 1H), 2.66 (s, 3H). TLC: 10% EtOAc Hexane (R1 0.5).

Reference： [1]Current Patent Assignee: DENALI THERAPEUTICS INC - WO2016/201168, 2016, A1 Location in patent: Paragraph 0424; 0425

55
[ 1927-94-2 ]
2-cyanomethyl-1-methylisoquinolinium bromide [ No CAS ]
12-chloro-14a-methyl-14aH-chromeno[2',3':4,5]imidazo[2,1-a]isoquinoline [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
48%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In methanol; water at 20℃; for 2h;	12-Chloro-14a-methyl-14aH-chromeno[2',3':4,5]imidazo-[2,1-a]isoquinoline (3d). Method I. 3-Chlorosalicylic aldehyde(106 mg, 0.68 mmol) and Na2CO3 (16 mg, 0.15 mmol)were added to a solution of salt 2a (200 mg, 0.76 mmol) in4:1 MeOH-H2O mixture (5 ml). The reaction mixture wasrefluxed for 2.5 h. The precipitate that formed was filteredoff, washed first with methanol, then two times with water,and again with methanol. Yield 71 mg (33%).Method II. 3-Chlorosalicylic aldehyde (165 mg, 1.05 mmol)and DBU (39 µl, 0.26 mmol) were added to a solution ofsalt 2a (70 mg, 0.26 mmol) in 5:1 MeOH-H2O mixture(2.1 ml). The reaction mixture was stirred at roomtemperature for 2 h. The precipitate that formed wasfiltered off, washed first with methanol, then two timeswith water, and again with methanol. Yield 40 mg (48%),yellow crystals, mp 223-224° (decomp.). 1H NMRspectrum, δ, ppm (J, Hz): 1.57 (3H, s, CH3); 5.76 (1H, s,H-8); 6.08 (1H, d, J = 7.5, H-5); 6.67 (1H, d, J = 7.5, H-6);6.95-6.99 (2H, m, H-9,11); 7.12-7.15 (2H, m, H-4,10);7.22-7.30 (2H, m, H-2,3); 7.63 (1H, d, J = 6.9, H-1). 13CNMR spectrum, δ, ppm (J, Hz): 29.9; 88.5; 94.4; 110.4;121.6 (2); 123.4; 124.1; 124.3; 124.7; 125.7; 126.3;127.8; 128.0; 129.0; 133.3; 135.4; 144.3; 161.0. Massspectrum, m/z: 321 [M+H]+. Found, %: C 71.12; H 4.06;N 8.85. C19H13ClN2O. Calculated, %: C 71.14; H 4.08;N 8.73.
48%	With 1,8-diazabicyclo[5.4.0]undec-7-ene In methanol; water at 20℃; for 2h;	12-Chloro-14a-methyl-14aH-chromeno[2',3':4,5]imidazo-[2,1-a]isoquinoline (3d) Method I. 3-Chlorosalicylic aldehyde(106 mg, 0.68 mmol) and Na2CO3 (16 mg, 0.15 mmol)were added to a solution of salt 2a (200 mg, 0.76 mmol) in4:1 MeOH-H2O mixture (5 ml). The reaction mixture wasrefluxed for 2.5 h. The precipitate that formed was filteredoff, washed first with methanol, then two times with water,and again with methanol. Yield 71 mg (33%).Method II. 3-Chlorosalicylic aldehyde (165 mg, 1.05 mmol)and DBU (39 μl, 0.26 mmol) were added to a solution ofsalt 2a (70 mg, 0.26 mmol) in 5:1 MeOH-H2O mixture (2.1 ml). The reaction mixture was stirred at roomtemperature for 2 h. The precipitate that formed wasfiltered off, washed first with methanol, then two timeswith water, and again with methanol. Yield 40 mg (48%),yellow crystals, mp 223-224°C (decomp.). 1H NMR spectrum, δ, ppm (J, Hz): 1.57 (3H, s, CH3); 5.76 (1H, s,H-8); 6.08 (1H, d, J = 7.5, H-5); 6.67 (1H, d, J = 7.5, H-6);6.95-6.99 (2H, m, H-9,11); 7.12-7.15 (2H, m, H-4,10);7.22-7.30 (2H, m, H-2,3); 7.63 (1H, d, J = 6.9, H-1). 13CNMR spectrum, δ, ppm (J, Hz): 29.9; 88.5; 94.4; 110.4;121.6 (2); 123.4; 124.1; 124.3; 124.7; 125.7; 126.3;127.8; 128.0; 129.0; 133.3; 135.4; 144.3; 161.0. Massspectrum, m/z: 321 [M+H]+. Found, %: C 71.12; H 4.06;N 8.85. C19H13ClN2O. Calculated, %: C 71.14; H 4.08;N 8.73.

Reference： [1]Voskressensky, Leonid G.; Sokolova, Ekaterina A.; Festa, Aleksey A.; Enina, Dorateya A.; Aksenov, Alexander V.; Varlamov, Aleksey V. [Chemistry of Heterocyclic Compounds, 2016, vol. 52, # 6, p. 415 - 420][Khim. Geterotsikl. Soedin., 2016, vol. 52, # 6, p. 415 - 420,6]
[2]Aksenov, Alexander V.; Enina, Dorateya A.; Festa, Aleksey A.; Sokolova, Ekaterina A.; Varlamov, Aleksey V.; Voskressensky, Leonid G. [Chemistry of Heterocyclic Compounds, 2016, vol. 52, # 6, p. 415 - 420][Khim. Geterotsikl. Soedin., 2016, vol. 52, # 6, p. 415 - 420,6]

56
[ 1927-94-2 ]
[ 75-05-8 ]
[ 223778-54-9 ]

Reference： [1]Synlett,2017,vol. 28,p. 475 - 480

57
[ 1927-94-2 ]
[ 106-95-6 ]
[ 1106304-55-5 ]

Yield	Reaction Conditions	Operation in experiment
85%	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 2h; Inert atmosphere;	3-Chloro-2-(prop-2-en-1-yloxy)benzaldehyde, 43 General procedure: To a suspension of K2CO3 (1.5 eq.) in DMF (2.0 M) was added salicylaldehyde (1.0 eq.) followed byallyl bromide (2.5 eq.). The resulting suspension was stirred at rt until TLC showed no startingmaterial remained. The reaction mixture was then separated between EtOAc (10 mL) and H2O(20 mL). The organic layer was washed with H2O (20 mL), dried (MgSO4), filtered and concentrated in20vacuo to give a crude material. The crude material was purified by flash column chromatography toafford the desired aldehyde.
	With potassium carbonate In N,N-dimethyl-formamide
	With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 15h;

With potassium carbonate In N,N-dimethyl-formamide at 70℃; for 2h;

4.2. General Procedure for the Preparation of Substrates 1 [20] and 2 [18,22] General procedure: A solution of salicylaldehyde (5 mmol) in dry DMF (10.0 mL) was treated with K2CO3 (7.0 mmol) and allyl bromide (6.0 mmol). The mixture was stirred 2 h at 70 °C. Then it was cooled to room temperature and poured into saturated aqueous NH4Cl and extracted 4 times with EtOAc. The organic phases were evaporated and then subjected to column chromatography to afford the starting materials 1.

Reference： [1]Craven, Philip; Aimon, Anthony; Dow, Mark; Fleury-Bregeot, Nicolas; Guilleux, Rachel; Morgentin, Remy; Roche, Didier; Kalliokoski, Tuomo; Foster, Richard; Marsden, Stephen P.; Nelson, Adam [Bioorganic and Medicinal Chemistry, 2015, vol. 23, # 11, p. 2629 - 2635]
[2]Ohno, Shohei; Takamoto, Kohei; Fujioka, Hiromichi; Arisawa, Mitsuhiro [Organic Letters, 2017, vol. 19, # 9, p. 2422 - 2425]
[3]Hu, Hao; Chen, Xiaolan; Sun, Kai; Wang, Junchao; Liu, Yan; Liu, Hui; Fan, Lulu; Yu, Bing; Sun, Yuanqiang; Qu, Lingbo; Zhao, Yufen [Organic Letters, 2018, vol. 20, # 19, p. 6157 - 6160]
[4]Liu, Qiang; Xie, Guanqun; Wang, Qiang; Mo, Zhendong; Li, Chen; Ding, Shujiang; Wang, Xiaoxia [Tetrahedron, 2019, vol. 75, # 41]

58
[ 634-95-7 ]
[ 1927-94-2 ]
[ 1581705-57-8 ]

Yield	Reaction Conditions	Operation in experiment
90.7%	With bis(triphenylphosphine)nickel(II) chloride; 1,10-phenanthroline-5,6-dione In N,N-dimethyl-formamide; acetonitrile at 50℃; for 1h;	2 Example 2 To the reactor was added 100 ml of a mixed organic solvent of N, N-dimethylformamide and acetonitrile in a volume ratio of 2: 1, 10 mmol of the compound of the above formula (I), 12 mmol of the compound of the formula (II) , 1.6 mmol of catalyst bis (triphenylphosphine) nickel chloride (NiCl2(PPh3)2), 2.0 mmol of ligand L1, heated to 50 ° C with stirring, and the reaction was stirred at this temperature for 1 hour.After completion of the reaction, all volatiles were removed in vacuo and the product was extracted with ethyl acetate. The solvent was removed from the organic phase and the resulting residue was chromatographed on a 300-400 mesh silica gel column to give the compound of formula (III) above 90.7% The1H NMR (D. 6-DMSO, 400 MHz): [delta] 10.14 (S, IH), 7.79 (D, J = 8.0 Hz, IH), 7.69 (D, J = 8.0 Hz, IH), 7.30 (T, J = 8.0 Hz, IH ), 3.41-3.58 (m, 4H), 1.19-1.38 (m, 6H) ppm.

Reference： [1]Current Patent Assignee: QINGDAO ZHONGKEQINGHUAN BIOTECHNOLOGY - CN106543040, 2017, A Location in patent: Paragraph 0021; 0023; 0024; 0025; 0026

59
[ 553-86-6 ]
[ 1927-94-2 ]
8-chloro-3-(2-hydroxyphenyl)coumarin [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
74%	With N,N,N',N'-tetramethylguanidine; In chloroform; at 20℃; for 3h;Sealed tube;	0.20 mmol of compound 5,0.24 mmol of compound 2e,0.02 mmol TMG and 2.0 mL chloroform were added to the sealed tube, The reaction at room temperature for 3h.After removing the solvent,The residue was purified by silica gel column chromatography to afford the product 6e,The yield is 74%.

Reference： [1]Organic and Biomolecular Chemistry,2017,vol. 15,p. 7505 - 7508
[2]Patent: CN107382933,2017,A .Location in patent: Paragraph 0186-0188

60
[ 1927-94-2 ]
[ 68-35-9 ]
4-[(3-chloro-2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzenesulfonamide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 20℃; for 5h; Reflux;	3.1.2. Synthesis General procedure: Sulfadiazine 1 (1 mmol, 250.3 mg) was suspended in methanol (MeOH, 10 mL), and 1.1 mmol ofthe appropriate aldehyde was added in one portion under vigorous stirring. The solution was refluxedfor 5 h and then stirred at room temperature overnight. The resulting crystals were filtered off, washedwith a small amount of MeOH and then acetonitrile, and dried. The crystals were recrystallizedfrom MeOH or tetrahydrofuran/n-hexane mixture if necessary. The identity of known compounds(i.e., 2a, 2c, 2d, and 2m) was confirmed by NMR (1H and 13C) and IR spectroscopy. All spectroscopic characteristics were in accordance with previously reported data. The purity was checked additionallyby melting points measurement and elemental analysis. The numbering of hydrogen atoms in the1H-NMR spectra is depicted in Figure 3.

Reference： [1]Krátký, Martin; Dzurková, Magdaléna; Janoušek, Jiří; Konečná, Klára; Trejtnar, František; Stolaříková, Jiřina; VinŠová, Jarmila [Molecules, 2017, vol. 22, # 9]

61
[ 534-22-5 ]
[ 1927-94-2 ]
4-[7-chloro-3-(5-methylfuran-2-yl)-1-benzofuran-2-yl]butan-2-one [ No CAS ]
8-chloro-2,4-dimethyl-4-(5-methylfuran-2-yl)-5,6-dihydro-4H-furo[2',3':3,4]cyclohepta[1,2-b][1]benzofuran [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
1: 80% 2: 15%	With copper(ll) bromide In 1,2-dichloro-ethane at 85℃; for 3h;	4.5 General procedure for the preparation of compounds 9-11 General procedure: Copper(II) bromide (33.5 mg, 0.15 mmol) was added to a stirred solution of benzaldehyde 8 (1.5 mmol) and 2-substituted furan 2 (7.5 mmol) in DCE (4 mL) in a 5 mL Wheaton V-vial, containing a stirring bar and Teflon pressure cap. The microreactor was placed into a preheated (85 °C) aluminum block and the resulting solution stirred for 3 h at this temperature. After completion of the reaction, the mixture was concentrated in vacuo and the residue was purified by flash column chromatography (silica gel, petroleum ether/CH2Cl2) to afford the corresponding products.

Reference： [1]Makarov, Anton S.; Kekhvaeva, Anna E.; Hall, Christopher J.J.; Price, Daniel R.; Trushkov, Igor V.; Uchuskin, Maxim G. [Tetrahedron, 2017, vol. 73, # 50, p. 7042 - 7053]

62
[ 43038-36-4 ]
[ 1927-94-2 ]
C₁₅H₁₀ClN₃O₂ [ No CAS ]

Reference： [1]Chinese Journal of Chemistry,2018,vol. 36,p. 698 - 707

63
[ 623-73-4 ]
[ 1927-94-2 ]
[ 1169490-56-5 ]

Yield	Reaction Conditions	Operation in experiment
	Stage #1: diazoacetic acid ethyl ester; 3-chlorosalicylaldehyde With tetrafluoroboric acid diethyl ether complex In dichloromethane at 38℃; Stage #2: With sulfuric acid for 0.0833333h;	43A ethyl 7-chlorobenzofuran-3-carboxylate HBF4.OEt2 (tetrafluoroboric acid diethyl ether complex) was added to 3-chloro-2-hydroxybenzaldehyde (6 g, 38.3 mmol) in CH2Cl2 (60 mL). A solution of ethyl diazoacetate (80 mL, 61.3 mmol) in CH2Cl2 (30 mL) was introduced into the reaction mixture as the evolution of N2 gas permitted (ca. 3-6 minute addition time) and the reaction was not allowed to go above 38° C. Once gas evolution ceased, the reaction mixture was concentrated by rotary evaporator and concentrated H2SO4 (0.3 to 0.5 mL) was added to the mixture while stirring. After 5 to 10 minutes, the mixture was diluted with CH2Cl2 (100 mL) and the H2SO4 was quenched with solid NaHCO3. The mixture was filtered through silica gel (100 g) and concentrated by rotary evaporation to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.30 (s, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.50-7.23 (m, 2H), 4.42 (dd, J=14.2, 7.1 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). MS (ESI+) m/z 225 (M+H)+.

Reference： [1]Current Patent Assignee: ABBVIE INC; GALAPAGOS - US2018/244640, 2018, A1 Location in patent: Paragraph 0991

64
[ 1927-94-2 ]
[ 70987-78-9 ]
(R)-3-chloro-2-(oxiran-2-ylmethoxy)benzaldehyde [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 3h;	General procedure: To a DMF (25mL) solution of 2-hydroxy-5-methoxybenzaldehyde (2.0g, 13.2mmol) were added potassium carbonate powder (2.2g, 15.8mmol) and epichlorohydrin (1.34mL, 17.2mmol). The resulting suspension was heated to 80C for 3h. The reaction mixture was cooled to ambient temperature and added AcOEt and water. The extracts are combined, and washed by brine, then dried over anhydrous Na2SO4. The mixture was concentrated in vacuo and purified by column chromatography (ethyl acetate: petroleum ether=1:10) to give compound22a(1.6g, 58%) as a colorless oil.
63%	With potassium carbonate; In N,N-dimethyl-formamide; at 80℃; for 4h;	General procedure: 5-bromosalicylaldehyde (5.0 g, 25 mmol) was dissolved in N,N-dimethylformamide (80 mL). add potassium carbonate (6.91 g, 50 mmol) and epichlorohydrin (2.94 mL, 37.5 mmol) was heated to 80 C and stirred for 4 h. The reaction was monitored by TLC (petroleum ether / ethyl acetate = 5/1). After the reaction mixture was completed, it was cooled to room temperature, diluted with water and extracted twice with ethyl acetate. The organic phase was combined, washed with water and brine, dried over anhydrous sodium sulfate. Filtered and the solvent was evaporated and the crude product purified by column chromatography (petroleum ether / ethyl acetate = 10/1), After purification, 3.2 g of a colorless liquid was obtained in a yield of 50%.

Reference： [1]Bioorganic and Medicinal Chemistry,2018,vol. 26,p. 5780 - 5791
[2]Patent: CN110092774,2019,A .Location in patent: Paragraph 0096-0099; 0483-0486

65
[ 1927-94-2 ]
[ 41978-69-2 ]
ethyl 2-(2-chloro-6-formylphenoxy)propanoate [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
100%	With potassium carbonate; potassium iodide In N,N-dimethyl-formamide at 80℃; for 0.666667h; Inert atmosphere;	B.B.1.B.1.1.B.1.1.3 To a solution of 3-chloro-2-hydroxybenzaldehyde (5.00 g, 31.93 mmol) in anh. DMF (30 mL) at RT are added successively ethyl 2-bromopropanoate (4.52 mL, 34.80 mmol), potassium carbonate (4.58 g, 33.13 mmol) and potassium iodide (262 mg, 1.57 mmol). The RM is heated to 80°C, under nitrogen, for 40 min. The RM is then allowed to cool to RT. Water (100 mL) and Et20 (150 mL) are added and the layers are separated. The aq. layer is extracted twice with Et20 and the combined organic layers are washed with brine, dried over anh. MgSC>4, filtered and concentrated to dryness under reduced pressure giving ethyl 2-(2-chloro-6-formylphenoxy)propanoate as a light brown oil (8.20 g, quantitative). LC-MS A: tR = 0.88 min; [M+H]+ = 256.99.

Reference： [1]Current Patent Assignee: IDORSIA PHARMACEUTICALS LTD - WO2018/210987, 2018, A1 Location in patent: Page/Page column 94

66
[ 19307-74-5 ]
[ 1927-94-2 ]
C₁₈H₁₅ClO₃ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
86%	With triphenylphosphine In methanol; dichloromethane at 20℃; for 36h;

Reference： [1]Deng, Zhi-Xiong; Xie, Zhen-Zhen; Zheng, Yu; Xiao, Jun-An; Wang, Rui-Jia; Xiang, Hao-Yue; Yang, Hua [Organic and Biomolecular Chemistry, 2019, vol. 17, # 8, p. 2187 - 2191]

67
[ 932-52-5 ]
[ 1927-94-2 ]
(E)-5-{(3-chloro-2-hydroxybenzylidene)amino}pyrimidine-2,4(1H,3H)-dione [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
97%	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

68
[ 1927-94-2 ]
[ 10424-38-1 ]
C₁₇H₁₆Cl₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
	In methanol at 80℃; for 3h;	2.2.1. Synthesis of halogenated Schiff base ligand General procedure: The halogenated tetradentate Schiff base ligand H2L1 and H2L2were prepared by mixing salicylaldehyde (3-chlorosalicylaldehydand 3-bromosalicylaldehyd for 1 and 2, respectively) (2.0 mmol)and 1,2-diaminopropane (0.06 g, 0.1 mmol) in 30 mL of methanol.The obtained solution was stirred and refluxed at 80 °C for threehours, then the solvent was removed by rotary evaporator to giveyellow powderproduct (Scheme 1).

Reference： [1]Wu, Qiong; Tang, Yafang; Zi, Qiaoli [Polyhedron, 2019, vol. 166, p. 123 - 129]

69
[ 120-72-9 ]
[ 1927-94-2 ]
2-chloro-6-[di(1H-indol-3-yl)methyl]phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
89%	With phospho sulphonic acid In water at 100℃; for 2.33333h; Green chemistry;	General Procedure for the Preparationof Bis(Indolyl)Alkanes General procedure: In 100-mL round bottom flask, a mixture of aldehyde(1 mmol) and indole (2 mmol) was charged to a stirring solution of phospho sulfonic acid (0.06 g) inH2O (40 mL), and the resulting reaction contents was vigorously stirred at 100°C for appropriate period oftime (2-3 h). After completion of the reaction, asobserved by thin-layer chromatography (EtOAc : PETether = 1 : 2), the reaction content was filtered and washed with distilled water to separate the catalyst.The residue contains crude bis(indolyl)alkane productsand filtrate contains phospho sulfonic acid(recovered catalyst). The resulting residue was decontaminated via silica gel-mediated chromatographic purification technique using EtOAc in PET ether solution (2 : 8) as eluent to furnish the required products.After washing filtrate with EtOAc and then drying,the obtained phospho sulfonic acid was reused for subsequent reactions. All the products were identified by comparing the analytical data (melting point, IR,1H NMR) with those reported data.

Reference： [1]Faisal, Muhammad; Larik, Fayaz Ali; Salman, Muhammad; Saeed, Aamer [Kinetics and Catalysis, 2019, vol. 60, # 4, p. 522 - 535]

70
[ 1927-94-2 ]
[ 5720-07-0 ]
2-(bis(4-methoxyphenyl)methyl)-6-chlorophenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
75%	With triethylamine In 1,2-dichloro-ethane at 80℃; for 15h; Schlenk technique;

Reference： [1]Chandra Nandi, Ganesh; Haritha Mercy, A. Antony; Jesin C. P., Irfana; Kataria, Ramesh; S., Ravindra [Journal of Organic Chemistry, 2020, vol. 85, # 5, p. 3000 - 3009]

71
[ 6165-69-1 ]
[ 1927-94-2 ]
2-chloro-6-(di(thiophen-3-yl)methyl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
64%	With triethylamine In 1,2-dichloro-ethane at 80℃; for 15h; Schlenk technique;

Reference： [1]Chandra Nandi, Ganesh; Haritha Mercy, A. Antony; Jesin C. P., Irfana; Kataria, Ramesh; S., Ravindra [Journal of Organic Chemistry, 2020, vol. 85, # 5, p. 3000 - 3009]

72
[ 1927-94-2 ]
[ 133730-34-4 ]
2-(bis(2,4-dimethoxyphenyl)methyl)-6-chlorophenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
66%	With triethylamine In 1,2-dichloro-ethane at 80℃; for 15h; Schlenk technique;

Reference： [1]Chandra Nandi, Ganesh; Haritha Mercy, A. Antony; Jesin C. P., Irfana; Kataria, Ramesh; S., Ravindra [Journal of Organic Chemistry, 2020, vol. 85, # 5, p. 3000 - 3009]

73
[ 1927-94-2 ]
[ 18531-95-8 ]
C₃₄H₂₂Cl₂N₂O₂ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
85%	In ethanol for 6h; Reflux;	3 Example 3 In a 1000ml flask, add 71g (0.25mol) binaphthalene diamine (DABN), 117g (0.5mmol) 5-chlorosalicylic aldehyde, 500ml absolute ethanol, react at the reflux temperature of ethanol for 6h, then cool, filter, and use CH2Cl2/petroleum ether column chromatography separated a yellow solid, which was then recrystallized from absolute ethanol to obtain 119.2 g of a yellow solid (H2L3) with a yield of 85%.

Reference： [1]Current Patent Assignee: CHINESE ACADEMY OF SCIENCES; Dalian Institute of Chemical Physics (in: CAS) - CN111138312, 2020, A Location in patent: Paragraph 0066-0070

74
[ 1927-94-2 ]
[ 22227-25-4 ]
3-trifluoromethyl-N'-(3-chloro-2-hydroxybenzylidene)benzohydrazide [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
71%	With acetic acid In methanol at 20℃;

Reference： [1]Del Poeta, Maurizio; Haranahalli, Krupanandan; Lazzarini, Cristina; Mallamo, John; McCarthy, J. Brian; Ojima, Iwao; Pathiranage, Senuri; Sun, Yi; Zambito, Julia [Journal of Medicinal Chemistry, 2019]

75
[ 2033-24-1 ]
[ 1927-94-2 ]
8-chloro-2-oxo-2H-chromene-3-carboxylic acid [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
96%	With [Cd₂(2,2'-((1,4-phenylenebis(methylene))bis((pyridin-2-ylmethyl)azanediyl))diacetamide)(fumarate)₂(H₂O)₂]*2H₂O In methanol at 26 - 28℃; for 3h;

Reference： [1]Khullar, Sadhika; Mandal, Sanjay K.; Markad, Datta [Inorganic Chemistry, 2020]

76
[ 1927-94-2 ]
2-fluoro-6-(hydroxyl(pyridine-2-yl)methyl)phenol [ No CAS ]
2-chloro-6-(1-(3-fluoro-2-hydroxyphenyl)imidazo[1,5-a]pyridin-3-yl)phenol [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
8%	With ammonium acetate; acetic acid at 110℃; for 18h; Sealed tube;	General procedure: Intermediates I, II or III (l.Oeq), aldehyde (1.5-3eq) and ammonium acetate (5-10eq) were suspended in acetic acid in a sealed vial. The contents were heated at between 80-110°C for 16-24h then cooled. The reaction mixture was poured onto iced water and the product isolated either by filtration or extraction and the crude product further purified, if required, by trituration, crystallisation or flash chromatography.; The title compound was prepared employing the general method H using (2-hydroxyphenyl)(pyridin- 2-yl)methanone (50mg) and 3-((dimethylamino)methyl)-2-hydroxybenzaldehyde (120mg) along with ammonium acetate (800mg) in acetic acid (2mL). The reaction was heated at 110°C for 17h before pouring the reaction into ice water. The crude product was isolated by extraction with EtOAc and further purified by flash chromatography on 12g S1O2 using EtOAc as the eluent. The target fractions were combined and evaporated to yield a solid which was sonicated in ethanol, filtered, washed with ethanol and air dried to yield the title compound (37mg) as a yellow solid.

Reference： [1]Current Patent Assignee: ALTERITY THERAPEUTICS - WO2020/186291, 2020, A1 Location in patent: Page/Page column 49; 50; 55

77
[ 1927-94-2 ]
[ 1423-60-5 ]
C₁₅H₁₃ClO₄ [ No CAS ]

Yield	Reaction Conditions	Operation in experiment
73%	With sodium acetate; P(p-C₆H₄F)3 In tetrahydrofuran at 30℃; for 24h; Molecular sieve;

Reference： [1]Chen, Kai; Chen, Yan-Shan; Deng, Zhi-Xiong; Xiang, Hao-Yue; Xiao, Jun-An; Xie, Zhen-Zhen; Yang, Hua; Zheng, Yu [Organic and Biomolecular Chemistry, 2020, vol. 18, # 43, p. 8916 - 8920]

78
[ 1927-94-2 ]
[ 619-45-4 ]
methyl (E)-4-[(3-chloro-2-hydroxybenzylidene)amino]benzoate [ No CAS ]