Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]=[C:10]1[NH:14][CH2:13][CH2:12][N:11]1[O:15][CH2:16][CH2:17][CH2:18][C:19]([O:21]CC)=[O:20].[OH-].[Na+]>C(O)C>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[N:9]=[C:10]1[NH:14][CH2:13][CH2:12][N:11]1[O:15][CH2:16][CH2:17][CH2:18][C:19]([OH:21])=[O:20]
Reactant: CCOC(=O)CCCON1CCNC1=Nc1c(Cl)cccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C(O)CCCON1CCNC1=Nc1c(Cl)cccc1Cl
Reaction time: 8 h

Procedure:
4.80 g. of ethyl 4-{[2-[(2,6-dichlorophenyl)imino]-1-imidazolidinyl]oxy}butyrate are dissolved in 100 ml. of ethanol, 26.6 ml. of 1N caustic soda solution are added at room temperature and the mixture is left to stand overnight. The solution is then neutralized with 26.6 ml. of 1N hydrochloric acid and evaporated in vacuo. The dried residue is digested with a hot 1:1 mixture of acetonitrile/ethyl acetate/chloroform. The salt is then filtered off from the solution and the filtrate is evaporated in vacuo. The residue is recrystallized from hot acetonitrile, whereupon 4-{[2-[(2,6-dichlorophenyl)imino]-1-imidazolidinyl]oxy}-butyric acid, m.p. 115°-116° (from acetonitrile) is obtained.
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[NH:10][C:11](=S)[S-:12].C([NH+](CC)CC)C.C(N(CC)CC)C.C(Cl)(=O)OCC>C(Cl)(Cl)Cl>[F:1][C:2]1[C:7]([F:8])=[C:6]([F:9])[CH:5]=[CH:4][C:3]=1[N:10]=[C:11]=[S:12]
Reactant: Fc1ccc(NC(=S)[S-])c(F)c1F
Agent: CCOC(=O)Cl
Agent: CC[NH+](CC)CC
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Product: Fc1ccc(N=C=S)c(F)c1F
Reaction time: 1 h
Yield: 78.3 %

Procedure:
Triethylammonium N-(2,3,4-trifluorophenyl)dithiocarbamate (92.0 g) and triethylamine (31.5 g) were added to chloroform (360 ml) and thereto ethyl chlorocarbonate (33.8 g) was added dropwise at 2°-6° C. with stirring over a period of 1 hour. The mixture was stirred for 10 minutes and washed with 3N hydrochloric acid and then with water. The organic layer was dried over anhydrous magnesium sulfate and the solvent was distilled off under reduced pressure. The obtained residue ws purified by silica-gel column chromatography (Silica gel 60, 230-400 mesh, made by Merck Co., 220 g, eluent: hexane) under medium pressure, followed by distillation under reduced pressure to give the title compound (42.0 g) as colorless liquid, b.p.: 96°-97° C./17 mmHg.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH2:10]([CH2:12][NH2:13])[OH:11].[BH4-].[Na+]>C(O)C.CO>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH:13][CH2:12][CH2:10][OH:11])=[CH:4][CH:3]=1
Reactant: NCCO
Reactant: O=Cc1ccc(Cl)cc1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: OCCNCc1ccc(Cl)cc1
Temperature: 60 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
Substituted benzaldehyde (0.01 mol), such as 4-chloro benzaldehyde (1.4 g), was dissolved in dry ethanol (30 mL) and ethanolamine (0.61 g, 0.01 mol) was added. The reaction mixture was stirred overnight at 60° C. The ethanol was evaporated under reduced pressure to give a colorless oil. The oil was then dissolved in dry methanol (30 mL) and cooled in ice. Sodium borohydride (NaBH4, 0.57 g, 0.015 mol) was added slowly in portions, and the resulting solution was left overnight at room temperature. The solvent was evaporated in vacuo, and the residue was dissolved in water, and extracted with CH2Cl2 (3×20 mL). The organic layers were combined and dried with Na2SO4, filtered and evaporated in vacuo to give colorless oily residue, which was purified by column chromatography (silica gel CH2Cl2:MeOH=9:1) to give 2-(4-chlorobenzylamino)-ethanol (II-1, 1.83 g, 99%).
Reaction SMILES: [F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:9].[C:10]([O-])([O-])=O.[K+].[K+].IC>CN(C=O)C>[F:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[O:9][CH3:10]
Reactant: Oc1cccc(F)c1F
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: COc1cccc(F)c1F
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 75.4 %

Procedure:
2,3-Difluorophenol (4.55 g) was dissolved in DMF (25 mL) and was treated with powdered K2CO3 (6.0 grams) and the mixture was stirred at an ambient temperature for 10 minutes under nitrogen atmosphere. The mixture was treated with iodomethane (9.0 grams), and was stirred at room temperature for 18 hours. The reaction mixture was quenched with water and was extracted with ether. The ether extract was washed with water, dried (Na2SO4) and concentrated to afford 3.8 grams of title compound as amber oil. 1HNMR(CDCl3): δ 6.97(m, 1H), 6.78(m, 2H), 3.90(s, 3H). Step 2: 2,3-Difluoro-4-methoxybenzaldehyde.
Reaction SMILES: [C:1](OC(=O)C)(=[O:3])[CH3:2].[OH:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19].Cl>N1C=CC=CC=1>[C:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([OH:15])=[O:14])=[CH:11][C:10]=1[N+:18]([O-:20])=[O:19])(=[O:3])[CH3:2]
Reactant: O=C(O)c1ccc(O)c([N+](=O)[O-])c1
Reactant: CC(=O)OC(C)=O
Agent: Cl
Solvent: c1ccncc1
Product: CC(=O)Oc1ccc(C(=O)O)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 3 h

Procedure:
Acetic anhydride (550 ml) was added to a mixture of 4-hydroxy-3-nitrobenzoic acid (100 g) and pyridine (119.82 ml), and stirred for 3 hours at 25° C. The reaction solution was poured into a cooled hydrochloric acid solution, and the thus-precipitated crystals were filtered and washed with cold water. The crystals were recrystallized from ethyl acetate/hexane, thereby giving 85.45 g of the desired compound.
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14](=[O:21])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1C=CC(S(N[C@H]([C@@H](N)C2C=CC=CC=2)C2C=CC=CC=2)(=O)=O)=CC=1>>[CH2:1]([O:8][C:9]([N:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C@@H:14]([OH:21])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CCN(C(=O)OCc2ccccc2)c2ccccc21
Agent: Cc1ccc(S(=O)(=O)N[C@@H](c2ccccc2)[C@@H](N)c2ccccc2)cc1
Product: O=C(OCc1ccccc1)N1CC[C@H](O)c2ccccc21
Yield: 86.2 %

Procedure:
1-benzyloxycarbonyl-4-oxo-1,2,3,4-tetrahydroquinoline (281 mg), [RuCl2(benzene)]2 (25.0 mg) and (S,S)-TsDPEN (73.3 mg) were treated in the same manner as Example 4 to give 244 mg of (4S)-1-benzyloxycarbonyl-4-hydroxy-1,2,3,4-tetrahydroquinoline (optical purity: 97% ee, yield: 86%).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:22]=[CH:21][C:8]([O:9][C:10]2[CH:15]=[CH:14][C:13]([CH2:16][C:17]([O:19][CH3:20])=[O:18])=[CH:12][CH:11]=2)=[CH:7][CH:6]=1)(=[O:4])=[O:3].[Br:23]N1C(=O)CCC1=O.BrBr>C(Cl)(Cl)(Cl)Cl>[Br:23][CH:16]([C:13]1[CH:14]=[CH:15][C:10]([O:9][C:8]2[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:3])=[O:4])=[CH:22][CH:21]=2)=[CH:11][CH:12]=1)[C:17]([O:19][CH3:20])=[O:18]
Reactant: COC(=O)Cc1ccc(Oc2ccc(S(C)(=O)=O)cc2)cc1
Reactant: O=C1CCC(=O)N1Br
Agent: BrBr
Solvent: ClC(Cl)(Cl)Cl
Product: COC(=O)C(Br)c1ccc(Oc2ccc(S(C)(=O)=O)cc2)cc1

Procedure:
To a mixture of 0.80 g of methyl α-[p-(p-methylsulfonylphenoxy)phenyl]acetate and 0.49 g of N-bromosuccinimide in 12.5 ml of carbon tetrachloride is added several drops of carbon tetrachloride containing bromine. The mixture is stirred and refluxed for 3 days and the solvent removed under vacuum. The residue is dissolved in dichloromethane and filtered through a one inch by five inch column of silica gel. Evaporation of the filtrate gives the product as an oil.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)O1.Br[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:21]=1[F:27].[OH-].[Na+]>O1CCCC1>[F:26][C:22]1[C:21]([F:27])=[CH:20][CH:25]=[CH:24][C:23]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2
Reactant: Fc1cccc(Br)c1F
Reactant: CC1(C)OB(c2cccc3[nH]ccc23)OC1(C)C
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Fc1cccc(-c2cccc3[nH]ccc23)c1F
Temperature: 25 °C
Yield: 69.8 %

Procedure:
4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole 6b (1.22 g, 5 mmol) was dissolved in 20 ml of tetrahydrofuran under stirring, and added with 1-bromo-2,3-difluoro-benzene (0.97 g, 5 mmol), tetrakis (triphenylphosphine)palladium (0.17 g, 0.15 mmol) and sodium hydroxide solution (7 ml, 2 mol/L) under an argon atmosphere. Upon completion of the addition, the reaction system was stirred at 75° C. in an oil bath overnight. After thin lay chromatography showed the disappearance of starting materials, the reaction mixture was naturally cooled down to room temperature and extracted with ethyl acetate (20 ml×3). The combined organic extracts were washed with saturated brine (10 ml), dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 4-(2,3-difluoro-phenyl)-1H-indole 6c (800 mg, yield 70%) as a white solid.
Reaction SMILES: CC1(C)C(C)(C)OB([C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)O1.Br[C:20]1[CH:25]=[CH:24][CH:23]=[C:22]([F:26])[C:21]=1[F:27].[OH-].[Na+]>O1CCCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:26][C:22]1[C:21]([F:27])=[CH:20][CH:25]=[CH:24][C:23]=1[C:9]1[CH:17]=[CH:16][CH:15]=[C:14]2[C:10]=1[CH:11]=[CH:12][NH:13]2
Reactant: Fc1cccc(Br)c1F
Reactant: CC1(C)OB(c2cccc3[nH]ccc23)OC1(C)C
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Product: Fc1cccc(-c2cccc3[nH]ccc23)c1F
Temperature: 25 °C
Yield: 69.8 %

Procedure:
4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-indole 3b (1.22 g, 5 mmol) was dissolved in 20 mL of tetrahydrofuran under stirring under an argon atmosphere, and 1-bromo-2,3-difluoro-benzene (0.97 g, 5 mmol), tetrakis (triphenylphosphine) palladium (0.17 g, 0.15 mmol) and 7 mL of sodium hydroxide solution (2M) were then added to the solution. Upon completion of the addition, the reaction system was stirred at 75° C. in an oil bath overnight. The reaction was completed until TLC showed the disappearance of starting materials. The reaction mixture was naturally cooled down to room temperature and extracted with ethyl acetate (20 mL ×3). The combined organic extracts were washed with saturated brine (10 mL), dried over anhydrous sodium sulfate, filtered to remove the drying agent and concentrated under reduced pressure. The resulting solid was purified by silica gel column chromatography to give the title compound 4-(2,3-difluoro-phenyl)-1H-indole 3c (800 mg, yield 70%) as a white solid.
Reaction SMILES: C(N(CC)CC)C.[CH3:8][C:9]1[N:10]=[C:11]([NH2:27])[S:12][C:13]=1[C:14]1[N:15]=[C:16]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[S:17][CH:18]=1.[CH:28]1[N:32]=[CH:31][N:30]([C:33](N2C=NC=C2)=[O:34])[CH:29]=1.CN(C=O)C>C(Cl)Cl>[CH3:8][C:9]1[N:10]=[C:11]([NH:27][C:33]([N:30]2[CH:29]=[CH:28][N:32]=[CH:31]2)=[O:34])[S:12][C:13]=1[C:14]1[N:15]=[C:16]([C:19]([N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[O:20])[S:17][CH:18]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1nc(N)sc1-c1csc(C(=O)N2CCOCC2)n1
Solvent: CN(C)C=O
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1nc(NC(=O)n2ccnc2)sc1-c1csc(C(=O)N2CCOCC2)n1
Temperature: 45 °C
Reaction time: 8 h
Yield: 79 %

Procedure:
In a 20 ml vial under Ar, triethylamine (51 μl; 0.37 mmol; 1.10 eq.) is added to a stirred suspension of 4′-methyl-2-(morpholin-4-ylcarbonyl)-4,5′-bi-1,3-thiazol-2′-amine, obtained in step II as describe above (142.4 mg; 0.34 mmol; 1 eq.), and CDI (54.4 mg; 0.34 mmol; 1 eq.) in dry DCM (5 ml). DMF (0.30 ml) is added to help the solubility. The mixture is stirred at 45° C. overnight. No starting material can be detected by HPLC. The reaction mixture is cooled down to RT. The resulting precipitate is isolated by filtration, washed with diethyl ether and dried under vacuum, affording Intermediate 7 (107.1 mg; 79%). It is used in the next step without further purification.
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[OH-].[Na+].[C:13](Cl)(=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21].Cl>O.C(O)(C)C>[C:13]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)(=[O:22])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH3:21]
Reactant: O=C(O)c1ccc(O)cc1
Reactant: CCCCCCCCC(=O)Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: CCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
69.1 g (0.5 mol) of para-hydroxybenzoic acid were first dissolved in 200 ml of water and 300 ml of isopropanol and this solution was adjusted to a pH of 10.5 at 20 to 25° C. using 87.4 g of NaOH solution (32% strength by weight aqueous solution, 0.7 mol). Metered into this solution then at a pH of 10.5, over the course of three hours, were 88.3 g (0.5 mol) of nonanoyl chloride. The pH was held at 10.5 using 40.5 g of NaOH solution (32% strength by weight aqueous solution, 0.324 mol), and the temperature was held at 20 to 25° C. The batch was stirred for one hour thereafter. Subsequently the reaction mixture was adjusted to a pH of 7 at 20 to 25° C. using 5.3 g of HCl solution (32% strength by weight aqueous solution) and adjusted to a pH of 1.5 to 3 at 65 to 70° C. using 60 g of HCl solution (32% strength by weight aqueous solution). The reaction mixture was cooled to room temperature (25° C.) and the solid was filtered off on a suction filter and washed ten times with 150 ml of water. The yield after drying under reduced pressure at 100° C. was 121.3 g (87.2% of theory). According to HPLC and NMR measurement, the product was free from nonanoic acid and from unreacted para-hydroxybenzoic acid. The purity of the product is >99.9% by weight.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.Cl[C:8]1[C:13]([Cl:14])=[CH:12][C:11]([Cl:15])=[CH:10][N:9]=1>>[Cl:14][C:13]1[C:8]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[N:9][CH:10]=[C:11]([Cl:15])[CH:12]=1
Reactant: C1CNCCN1
Reactant: Clc1cnc(Cl)c(Cl)c1
Product: Clc1cnc(N2CCNCC2)c(Cl)c1

Procedure:
Piperazine (256 mg, 3.0 mmol, Aldrich) and 2,3,5-trichloropyridine (364 mg, 20 mmol, Aldrich) were reacted under the conditions of Example 3a to give the title compound as a light-yellow solid. MS (ESI, pos. ion) m/z: 232 (M+1).
Reaction SMILES: [O:1]1[CH2:6][CH2:5][C:4]([C:12]([O:14]CC)=[O:13])([C:7]([O:9]CC)=[O:8])[CH2:3][CH2:2]1.[OH-].[K+].O>C(O)C>[O:1]1[CH2:2][CH2:3][C:4]([C:7]([OH:9])=[O:8])([C:12]([OH:14])=[O:13])[CH2:5][CH2:6]1
Reactant: CCOC(=O)C1(C(=O)OCC)CCOCC1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: O=C(O)C1(C(=O)O)CCOCC1
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 90.6 %

Procedure:
To a stirred solution of diethyl oxane-4,4-dicarboxylate (40.0 g., 173 mmol) in ethanol (100 mL) was added a solution of potassium hydroxide (21.4 g, 382 mmol) in ethanol (300 mL). After the completion of the addition, the reaction mixture was stirred for 15 min at ambient temperature and then refluxed for 2.5 h. Water (40 mL) was added to the thick, white suspension, and then the solvent was removed by rotary evaporation. Water (40 mL) was added to the remaining residue and the resulting mixture then acidified with concentrated sulfuric acid (20 mL). The acidic solution was extracted with diethyl ether (3×300 mL) and the combined organic layers were dried (Na2SO4). Removal of solvent by rotary evaporation yielded the product (27.3 g, 90.2% yield).
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5](Br)=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>O1CCOCC1>[NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][C:5]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)=[CH:4][N:3]=1
Reactant: OB(O)c1ccc(F)cc1
Reactant: Nc1ncc(Br)cc1[N+](=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Product: Nc1ncc(-c2ccc(F)cc2)cc1[N+](=O)[O-]
Temperature: 110 °C
Yield: 100 %

Procedure:
5.0 g of 2-amino-5-bromo-3-nitropyridine are dissolved in 120 ml of anoxic dioxane under a nitrogen atmosphere. Subsequently, 69 ml of an aqueous sodium bicarbonate solution (2.0 M), 5.4 g of 4-fluorophenyl-boronic acid, and 1.0 g of trans-dichloro-bis(tricyclohexylphosphane)palladium-(II) are added. The reaction mixture is refluxed at 110° C. for 17 hours. Thereafter, the volatile components are removed in vacuo and the remaining residue is redissolved in 2.0 l of a mixture of water/dichloromethane (1:1). The aqueous phase is extracted four times each with 625 ml of dichloromethane. The organic layer is separated, dried using sodium sulfate, and evaporated to dryness to yield a colorless, crude solid. Subsequently, the residue is purified by flash chromatography on silica gel (eluent: toluene/ethyl acetate 20:1) to afford 5.35 g of the title compound as a colorless solid of m.p. 232° C. MS: 234.2 (MH+). TLC: Rf=0.30 toluene/ethyl acetate 20:1).
Reaction SMILES: CC(C)=O.C(OCC)C.[CH3:10][C@H:11]1[CH2:94]O[C@@:14]2(O[C@H:17]3[C@@H:19](O)[C@H:20]4[C@@H:25]5[CH2:26][CH2:27][C@H:28]6[CH2:33][C@@H:32]([O:34][C@@H]7O[C@H](CO)[C@H](O[C@@H]8O[C@H](CO)C(O)[C@H](O[C@@H]9OC[C@@H](O)[C@H](O)[C@H]9O)[C@H]8O[C@@H]8O[C@H](CO)[C@H](O)[C@H](O[C@@H]9O[C@H](CO)[C@@H](O)[C@H](O)[C@H]9O)[C@H]8O)[C@H](O)[C@H]7O)[C@H:31](O)[CH2:30][C@:29]6([CH3:89])[C@H:24]5[CH2:23][CH2:22][C@:21]4([CH3:90])[C@H:16]3[C@@H:15]2[CH3:92])[CH2:13][CH2:12]1>C(O)C>[CH3:94][CH:11]([CH2:12][CH2:13][CH2:14][C@H:15]([C@@H:16]1[C@:21]2([CH3:90])[C@H:20]([C@H:25]3[C@H:24]([CH2:23][CH2:22]2)[C@:29]2([CH3:89])[C:28]([CH2:33][C@H:32]([CH2:31][CH2:30]2)[OH:34])=[CH:27][CH2:26]3)[CH2:19][CH2:17]1)[CH3:92])[CH3:10]
Reactant: C[C@@H]1CC[C@@]2(OC1)O[C@H]1[C@@H](O)[C@H]3[C@@H]4CC[C@H]5C[C@@H](O[C@@H]6O[C@H](CO)[C@H](O[C@@H]7O[C@H](CO)C(O)[C@H](O[C@@H]8OC[C@@H](O)[C@H](O)[C@H]8O)[C@H]7O[C@@H]7O[C@H](CO)[C@H](O)[C@H](O[C@@H]8O[C@H](CO)[C@@H](O)[C@H](O)[C@H]8O)[C@H]7O)[C@H](O)[C@H]6O)[C@H](O)C[C@]5(C)[C@H]4CC[C@]3(C)[C@H]1[C@@H]2C
Solvent: CCO
Solvent: CCOCC
Solvent: CC(C)=O
Product: CC(C)CCC[C@@H](C)[C@H]1CC[C@H]2[C@@H]3CC=C4C[C@@H](O)CC[C@]4(C)[C@H]3CC[C@]12C
Temperature: 0 °C
Reaction time: 1.5 h

Procedure:
The whole mixture was incubated at 37° C. for 90 minutes, then the reaction was terminated by adding 1 mM of 15%-KOH (a 95% ethanol solution), next 2 mg of cholesterol was added thereto, saponified at 75° C. for 1 hour, and cholesterol was extracted with petroleum ether, the extract was concentrated to dryness. To the residue thus obtained was added with 2.5 ml of a mixture of acetone-diethyl ether (1:1) and 2.5 ml of 1%-digitonin (a 50% ethanol solution), then this solution was allowed to stand for 1 hour in cooling condition by using ice-water to precipitate cholesterol. The precipitate was washed with acetone, a mixture of acetonediethyl ether (1:1) and diethyl ether in this order, then the radioactivity of the residue was measured by using a liquid scintillation counter.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:4](=[O:14])[CH:5]2[CH:10]([C:11](=[O:13])[CH:12]=1)[CH2:9][CH:8]=[CH:7][CH2:6]2.N#N.C([O-])([O-])=O.[K+].[K+].Cl>CO>[CH3:1][O:2][C:3]1[CH:12]=[C:11]([OH:13])[C:10]2[CH2:9][CH:8]=[CH:7][CH2:6][C:5]=2[C:4]=1[OH:14]
Reactant: COC1=CC(=O)C2CC=CCC2C1=O
Agent: Cl
Agent: N#N
Agent: O=C([O-])[O-]
Solvent: CO
Product: COc1cc(O)c2c(c1O)CC=CC2
Temperature: 25 °C

Procedure:
A solution of 2-methoxy-4a,5,8,8a-tetrahydronaphthalene-1,4-dione (55, 542 mg, 2.82 mmol) in MeOH (50 mL) was purged with a stream of N2 for 5 min with stirring at rt. With continued N2 purging, solid K2CO3 (390 mg, 2.82 mmol, Baker) was added to the stirred solution. The solution immediately turned yellow. The reaction was allowed to stir for 15 min at rt under N2, after which it was brown. To this there was added a dilute HCl solution (10% concd HCl, 90% H2O, 50 mL) in one portion. The MeOH was removed in vacuo to give a colorless suspension. The suspended material was collected by filtration, washed with a dilute acid solution (as above, 4×6 mL) and dried in vacuo to yield a fluffy colorless solid (444 mg, 82%, pure by 1H NMR analysis (unstable on TLC)); mp 142.5°-144° C. (confirmed), lit. (Cavill et al., supra) 123°-124° C. (benzene/petroleum ether); 1H NMR (CDCl3) δ2.21 (m, 2H), 3.32 (m, 2H), 3.84 (s, 3H), 4.25 (s, 1H), 5.25 (s, 1H), 5.90 (m, 2H), 6.36 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:13]([Cl:14])=[CH:12][CH:11]=[C:10](F)[C:7]=1[CH:8]=O.O.[NH2:21][NH2:22]>C(O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:13]([Cl:14])=[CH:12][CH:11]=[C:10]2[C:7]=1[CH:8]=[N:21][NH:22]2
Reactant: NN
Reactant: O=Cc1c(F)ccc(Cl)c1Oc1cc(Cl)cc(Br)c1
Solvent: CCO
Solvent: O
Product: Clc1cc(Br)cc(Oc2c(Cl)ccc3[nH]ncc23)c1
Temperature: 25 °C

Procedure:
To a suspension of 2-(3-bromo-5-chlorophenoxy)-3-chloro-6-fluorobenzaldehyde (77.5 g, 213 mmol) in ethanol (120 mL) was added hydrazine hydrate (31 mL, 639 mmol). The resulting mixture was then heated at reflux for 4 days, after which the mixture was cooled to room temperature, diluted with water (100 mL) and the resulting solid was filtered. The solid was absorbed onto silica gel (300 g) and purified on a silica gel (1500 g) column (0-40% EtOAc/CH2Cl2) to give the title product as a white solid. LRMS (M+1)=358.8
Reaction SMILES: [N+:1]1([O-:9])[C:2]([CH3:8])=[CH:3][CH:4]=[CH:5][C:6]=1[CH3:7].[N+:10]([O-])([OH:12])=[O:11]>S(=O)(=O)(O)O>[N+:10]([C:4]1[CH:3]=[C:2]([CH3:8])[N+:1]([O-:9])=[C:6]([CH3:7])[CH:5]=1)([O-:12])=[O:11]
Reactant: O=[N+]([O-])O
Reactant: Cc1cccc(C)[n+]1[O-]
Agent: O=S(=O)(O)O
Product: Cc1cc([N+](=O)[O-])cc(C)[n+]1[O-]

Procedure:
A mixture of 2,6-lutidine 1-oxide (20, 15 g, 110 mmol) and concentrated sulfuric acid (98%, 30 ml) and concentrated nitric acid (70%, 12 ml) is heated under reflux for 3 hours. The mixture is poured into a large excess of ice and extracted with chloroform (3×100 ml). The combined chloroform extracts are washed with aqueous sodium hydroxide and water and dried over magnesium sulfate. Removal of the solvent yields pure yellow solid 4-Nitro-2,6-lutidine 1-oxide (21). 1H NMR (300 MHz, CDCl3) δ 2.64 (s, 6H), 8.08 (s, 2H). MS, m/z 169 (M+1), 210 (M+MeCN).