Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].O.[CH2:6]([O:8][C:9](=[O:54])[C:10]([CH3:53])([CH3:52])[CH2:11][C:12]1[N:13]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:45]=[N:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=3)=[CH:40][CH:39]=2)[C:14]2[C:19]([C:20]=1SC(C)(C)C)=[CH:18][C:17]([O:26][CH2:27][C:28]1[S:29][C:30]3[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=3[N:32]=1)=[CH:16][CH:15]=2)[CH3:7]>C(Cl)Cl>[CH2:6]([O:8][C:9](=[O:54])[C:10]([CH3:53])([CH3:52])[CH2:11][C:12]1[N:13]([CH2:37][C:38]2[CH:43]=[CH:42][C:41]([C:44]3[CH:45]=[N:46][C:47]([O:50][CH3:51])=[CH:48][CH:49]=3)=[CH:40][CH:39]=2)[C:14]2[C:19]([CH:20]=1)=[CH:18][C:17]([O:26][CH2:27][C:28]1[S:29][C:30]3[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=3[N:32]=1)=[CH:16][CH:15]=2)[CH3:7]
Reactant: CCOC(=O)C(C)(C)Cc1c(SC(C)(C)C)c2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2ccc(OC)nc2)cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Solvent: ClCCl
Product: CCOC(=O)C(C)(C)Cc1cc2cc(OCc3nc4ccccc4s3)ccc2n1Cc1ccc(-c2ccc(OC)nc2)cc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
Aluminum chloride (0.18 g, 1.37 mmol) was suspended in CH2Cl2 (1 mL), and water (19 uL, 11.0 mmol) was added slowly at room temperature. The mixture was stirred for 5 minutes, and then cooled to 0° C. 3-{5-(Benzothiazol-2-ylmethoxy)-3-tert-butylsulfanyl-1-[4-(6-methoxy-pyridin-3-yl)-benzyl]-1H-indol-2-yl}-2,2-dimethyl-propionic acid ethyl ester (0.12 g, 0.17 mmol) was added in CH2Cl2 (1 mL), and the reaction was stirred at room temperature for 2 hours. Once no starting material was observed by tlc, water was added and the mixture was extracted with CH2Cl2. The combined organic layers were washed with water, dried over MgSO4, filtered, and concentrated. The residue was purified to give the desired product (H-1).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4]([OH:6])=[O:5].[CH3:12][Si](C=[N+]=[N-])(C)C>C(OC(=O)C)C.C(O)C>[CH3:12][O:5][C:4](=[O:6])[C:3]1[C:7]([F:11])=[CH:8][CH:9]=[CH:10][C:2]=1[NH2:1]
Reactant: C[Si](C)(C)C=[N+]=[N-]
Reactant: Nc1cccc(F)c1C(=O)O
Solvent: CCOC(C)=O
Solvent: CCO
Product: COC(=O)c1c(N)cccc1F
Reaction time: 0.5 h
Yield: 99.9 %

Procedure:
Dissolve 2-Amino-6-fluoro-benzoic acid (3.00 g, 19.3 mmol) in ethylacetate (59 mL) and ethanol (59 mL) and add (trimethylsilyl) diazomethane (19.3 mL, 38.68 mmol, 2M in hexane) at room temperature and stir the solution for 1 h 30 min. Remove the solvent under reduced pressure to afford the title compound (3.26 g, quantitative). MS (ES+): 170 (M+H).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:32])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:22])([F:21])[F:20])=[CH:15][C:14]=2[CH2:23][NH:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1.[C:33](Cl)(=[O:35])[CH3:34]>>[CH3:1][O:2][C:3](=[O:32])[CH2:4][C:5]1[CH:6]=[C:7]([C:13]2[CH:18]=[CH:17][C:16]([C:19]([F:21])([F:20])[F:22])=[CH:15][C:14]=2[CH2:23][N:24]([C:33](=[O:35])[CH3:34])[CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C:8]([O:11][CH3:12])=[CH:9][CH:10]=1
Reactant: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CNCc2ccccc2)c1
Reactant: CC(=O)Cl
Product: COC(=O)Cc1ccc(OC)c(-c2ccc(C(F)(F)F)cc2CN(Cc2ccccc2)C(C)=O)c1

Procedure:
Prepared according to the procedure described in Example 1, Step 6, using the following starting materials: [2′-(benzylamino-methyl)-6-methoxy-4′-trifluoromethyl-biphenyl-3-yl]-acetic methyl ester and acetyl chloride.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1)=O.[NH2:16][OH:17].Cl.CCN(CC)CC>CCO>[F:1][C:2]([F:15])([F:14])[C:3]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([N+:11]([O-:13])=[O:12])[CH:6]=1)=[N:16][OH:17]
Reactant: NO
Reactant: O=C(c1cccc([N+](=O)[O-])c1)C(F)(F)F
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCO
Product: O=[N+]([O-])c1cccc(C(=NO)C(F)(F)F)c1
Yield: 79.5 %

Procedure:
A mixture of 2,2,2-trifluoro-1-(3-nitro-phenyl)ethanone (4 g), NH2OH.HCl (5.037 g), and Et3N (20.44 g) in EtOH (80 mL) was refluxed for 4 days. After concentration, the residue was extracted with CH2Cl2. The organic layer was washed with water and dried over MgSO4. The crude product was purified by silica gel flash chromatography (30% ethyl acetate in hexanes) to give the title compound (3.4 g) as a solid.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[C:6]([CH3:8])O[C:4](=[O:9])[CH:3]=1.[CH2:10]([NH2:13])[CH:11]=[CH2:12]>O>[CH2:10]([N:13]1[C:6]([CH3:8])=[CH:7][C:2]([OH:1])=[CH:3][C:4]1=[O:9])[CH:11]=[CH2:12]
Reactant: C=CCN
Reactant: Cc1cc(O)cc(=O)o1
Solvent: O
Product: C=CCn1c(C)cc(O)cc1=O
Temperature: 100 °C
Reaction time: 2 h
Yield: 68.1 %

Procedure:
4-hydroxy-6-methyl-2-pyrone (2 g, 16 mmol) was stirred in water (25 mL). Allylamine (1.2 ml, 16 mmol) was added to the reaction. The reaction was then heated to 100° C. at which point the reaction became homogeneous. The reaction was stirred at 100° C. for 2 h. The reaction was then allowed to cool to rt after which a white precipitate formed. The precipitate was isolated by suction filtration. After additional washing with water, 1.8 g (69%) of an off-white solid was obtained.
Reaction SMILES: [C:1](=[O:15])([O:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)[O:2][CH2:3]Cl.[I-:16].[Na+]>CC(C)=O>[C:1](=[O:15])([O:5][C:6]1[CH:11]=[CH:10][C:9]([N+:12]([O-:14])=[O:13])=[CH:8][CH:7]=1)[O:2][CH2:3][I:16]
Reactant: O=C(OCCl)Oc1ccc([N+](=O)[O-])cc1
Reactant: [I-]
Agent: [Na+]
Solvent: CC(C)=O
Product: O=C(OCI)Oc1ccc([N+](=O)[O-])cc1
Temperature: 40 °C
Reaction time: 5 h
Yield: 89 %

Procedure:
Chloromethyl p-nitrophenyl carbonate (52) (100 g, 0.43 moles), sodium iodide (228 g, 1.30 moles) and 50 g of dried molecular sieves (4 Å) were added to 2 L of acetone under nitrogen with mechanical stirring. The resulting mixture was stirred at 40° C. for 5 hours (monitored by 1H NMR). Upon completion, the solid materials were removed by filtration and the solvent was removed under reduced pressure. The residue was redissolved in dichloromethane (1 L) and washed twice with saturated aqueous sodium carbonate (300 mL) followed by water (300 mL). The organic layer was separated and dried over anhydrous sodium sulfate. Removal of solvent gave 123.6 g (89%) of the title compound (53) as a solid upon standing. The compound was found to be unstable to LC-MS. 1H NMR (CDCl3, 400 MHz): 6.06 (s, 2H), 7.42 (d, J=9 Hz, 2H), 8.30 (d, J=9 Hz, 2H). 13C NMR (CDCl3, 100 MHz): 155.1, 151.0, 146.0, 125.8, 125.7, 121.9, 33.5.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH:12]1[C:20]2[C:19]3[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=3[S:17][C:16]=2[CH:15]=[C:14]([CH:25]([N:27]2[CH:31]=[CH:30][N:29]=[CH:28]2)[CH3:26])[CH:13]=1.C(=O)(O)[O-].[Na+].[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41]>C(Cl)(Cl)Cl.CC(C)=O>[C:37]([OH:44])(=[O:43])/[CH:38]=[CH:39]/[C:40]([OH:42])=[O:41].[N:27]1([CH:25]([C:14]2[CH:13]=[CH:12][C:20]3[C:19]4[CH:21]=[CH:22][CH:23]=[CH:24][C:18]=4[S:17](=[O:9])[C:16]=3[CH:15]=2)[CH3:26])[CH:31]=[CH:30][N:29]=[CH:28]1
Reactant: CC(c1ccc2c(c1)sc1ccccc12)n1ccnc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C(O)/C=C/C(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClC(Cl)Cl
Solvent: CC(C)=O
Product: CC(c1ccc2c(c1)S(=O)c1ccccc1-2)n1ccnc1
Reaction time: 2 h
Yield: 63.6 %

Procedure:
Under ice-cooling, m-chloroperbenzoic acid (0.18 g) was gradually added in small portions to a solution of 1-[1-(dibenzothiophen-3-yl) ethyl]-1H-imidazole (0.2 g) obtained in Example 8 in chloroform (5 ml), and the mixture was stirred at the same temperature for 2 hours. A saturated sodium bicarbonate aqueous solution was added and the chloroform layer was separated and dried over anhydrous magnesium sulfate. After evaporation of the solvent, the resulting residue was purified by silica gel column chromatography to obtain an oily material from a chloroform-methanol (100:1) eluate. This oily material was dissolved in acetone and mixed with 40 mg of fumaric acid which was dissolved by heating. After cooling, the thus precipitated crystals were washed with acetone to obtain 90 mg of 3-[1-(1H-imidazo1-1-yl)ethyl]dibenzothiophene-5-oxide monofumarate.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([NH:6][CH:7]=[N:8]2)=[C:4]([Cl:11])[N:3]=1.CC([O:15][C@H:16]1[CH:20]=[CH:19][C@@H:18](O)[CH2:17]1)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:19]2[CH2:20][C@H:16]([OH:15])[CH:17]=[CH:18]2)=[C:4]([Cl:11])[N:3]=1
Reactant: CC(=O)O[C@H]1C=C[C@@H](O)C1
Reactant: Clc1nc(Cl)c2[nH]cnc2n1
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: O[C@@H]1C=C[C@H](n2cnc3c(Cl)nc(Cl)nc32)C1
Reaction time: 0.08 h

Procedure:
2,6-Dichloropurine (10 g, 52.90 mmol), (1S,4R)-cis-4-acetoxy-2-cyclopenten-1-ol (10 g, 70.40 mmol), tris(dibenzylideneacetone)dipalladium(0) (3.20 g, 3.50 mmol) and polymer supported triphenylphosphine (3 mmol/g, 11.60 g, 35.00 mmol) are placed in an oven-dried flask under an atmosphere of argon. Dry deoxygenated THF (80 mL) is added and the reaction mixture is stirred gently for 5 minutes. Triethylamine (20 mL) is added and the reaction mixture is stirred at 50° C. The reaction is shown to be complete by LCMS after 1 hour. The reaction mixture is allowed to cool, filtered and the solvent is removed in vacuo. The title compound is obtained after purification by flash column chromatography (silica, dichloromethane/methanol 25:1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:17]=[CH:18][CH:19]=1)[CH:5]=[C:6]1[CH2:10][N:9]([C:11]([OH:13])=[O:12])[CH:8]([C:14]([OH:16])=[O:15])[CH2:7]1.O.[OH-].[Li+]>O1CCCC1.O>[C:4]([O:12][C:11]([N:9]1[CH2:10][C:6](=[CH:5][C:4]2[CH:17]=[CH:18][CH:19]=[C:2]([F:1])[CH:3]=2)[CH2:7][CH:8]1[C:14]([OH:16])=[O:15])=[O:13])([CH3:17])([CH3:5])[CH3:3]
Reactant: O=C(O)C1CC(=Cc2cccc(F)c2)CN1C(=O)O
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CC(=Cc2cccc(F)c2)CC1C(=O)O
Temperature: 25 °C
Reaction time: 72 h
Yield: 153.2 %

Procedure:
To a stirred solution of 4-(3-Fluoro-benzylidene)-pyrrolidine-1,2-dicarboxylic acid 1-terf butyl ester 2-methyl ester (3.23 g, 9.63 mmol) in tetrahydrofuran (150 ml), was added 1M lithium hydroxide monohydrate (1.21 g, 28.9 mmol) in water (50 ml). The mixture was stirred at room temperature for 3 days. Tetrahydrofuran was removed by evaporation under reduced pressure, the residue diluted with water (30 ml) and acidified to pH 2.0-3.0 using 1M hydrochloric acid. The aqueous was extracted with diethyl ether (3×100 ml) and the combined organics dried over magnesium sulfate. The solvent was removed by evaporation under reduced pressure to give the title compound (2.37 g, 77%) as a white foam.
Reaction SMILES: [CH2:1]([N:8]1[C:16]2[C:15]3=[N:17][C@H:18]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:19][N:14]3[C:13](=[O:27])[N:12]([CH2:28][CH2:29][CH3:30])[C:11]=2[N:10]=[C:9]1Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[NH:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1.O>CN(C)C=O>[CH2:1]([N:8]1[C:16]2[C:15]3=[N:17][C@H:18]([CH2:20][C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[CH2:19][N:14]3[C:13](=[O:27])[N:12]([CH2:28][CH2:29][CH3:30])[C:11]=2[N:10]=[C:9]1[N:38]1[CH2:42][CH2:41][CH2:40][CH2:39]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CCCN1C(=O)N2C[C@@H](Cc3ccccc3)N=C2c2c1nc(Br)n2Cc1ccccc1
Reactant: C1CCNC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CCCN1C(=O)N2C[C@@H](Cc3ccccc3)N=C2c2c1nc(N1CCCC1)n2Cc1ccccc1
Temperature: 100 °C
Yield: 94.9 %

Procedure:
Compound 35 (500 mg, 1.05 mmol) obtained in Example 35 was dissolved in N,N-dimethylformamide (15 mL), to the solution were added potassium carbonate (430 mg, 3.11 mmol, 3.0 equivalents) and pyrrolidine (260 μL, 3.11 mmol, 3.0 equivalents), and then the mixture was stirred with heating at 100° C. for 3.5 hours. To the reaction solution was added water, the mixture was extracted with ethyl acetate, and the extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (chloroform:methanol=99:1 to 97:3), and to the residue were added acetone and diethyl ether. The deposited crystals were collected by filtration to obtain the title compound (467 mg, 95%) as white crystals.
Reaction SMILES: [H-].[Na+].[OH:3][C:4]1[C:5](=[O:16])[C:6]([CH2:14][OH:15])=[CH:7][CH:8]=[C:9]([CH:11]([CH3:13])[CH3:12])[CH:10]=1.[CH2:17](I)[CH3:18]>CN(C)C=O.ClCCl>[CH2:17]([O:3][C:4]1[C:5](=[O:16])[C:6]([CH2:14][OH:15])=[CH:7][CH:8]=[C:9]([CH:11]([CH3:13])[CH3:12])[CH:10]=1)[CH3:18]
Reactant: CCI
Reactant: CC(C)c1ccc(CO)c(=O)c(O)c1
Agent: [H-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CCOc1cc(C(C)C)ccc(CO)c1=O
Temperature: 70 °C
Yield: 37.5 %

Procedure:
60% oily sodium hydride (256 mg, 6.4 mmol) was added to a solution of 2-hydroxy-7-hydroxymethyl-4-isopropyl-2,4,6-cycloheptatrien-1-one (1.13 g, 5.82 mmol) in dimethylformamide (5 ml) with stirring. Then, ethyl iodide (0.7 ml, 8.75 mmol) was added and the reaction mixture was heated at 70° C. for 3 hours. The reaction solution was diluted with dichloromethane, washed with water, and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the residue was purified by silica gel column chromatography [eluent:hexane/ethyl acetate (2:3)] to give 485 mg of 2-ethoxy-7-hydroxymethyl 4-isopropyl-2,4,6-cycloheptatrien-1-one as a pale yellow amorphous powder (yield: 76%).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[C:8]([CH3:10])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].C([O-])([O-])=O.[Cs+].[Cs+].Br[CH2:18][C:19]#[N:20]>CC#N>[CH:4]([C:3]1[CH:6]=[CH:7][C:8]([CH3:10])=[CH:9][C:2]=1[O:1][CH2:18][C:19]#[N:20])=[O:5]
Reactant: N#CCBr
Reactant: Cc1ccc(C=O)c(O)c1
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC#N
Product: Cc1ccc(C=O)c(OCC#N)c1
Temperature: 25 °C
Reaction time: 6 h
Yield: 92.1 %

Procedure:
To a solution of 2-hydroxy-4-methylbenzaldehyde (12 g, 88 mmol) in 432 mL of CH3CN was added Cs2CO3 (34.5 g, 106 mmol) followed by 2-bromoacetonitrile (6.75 mL, 97 mmol), After the mixture was stirred at room temperature for 6 hr, the mixture was filtered through Celite to remove solid, washed with DCM, and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel flash chromatography, 100% Heptane-20% Ethyl Acetate/80% Heptane) to give a white solid, 2-(2-formyl-5-methylphenoxy)acetonitrile (14.2 g). LCMS retention time=1.06 minutes (LC method 3); MS (m+1)=175.8. 1H NMR (400 MHz, DMSO-d6) δ 2.41 (s, 3H), 5.33 (s, 2H), 7.05 (d, J=7.8 Hz, 1H), 7.20 (s, 1H), 7.68 (s, 1H), 10.26 (d, J=0.8 Hz, 1H).
Reaction SMILES: [CH2:1]([O:6][CH2:7][C:8]1[CH:26]=[CH:25][C:11]([C:12](OC2C=C(F)C(C#N)=C(F)C=2)=[O:13])=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH3:5].C(OCC1C=CC(C(O)=O)=CC=1)CCCC.S(Cl)([Cl:45])=O.N1C=CC=CC=1>C1(C)C=CC=CC=1>[CH2:1]([O:6][CH2:7][C:8]1[CH:26]=[CH:25][C:11]([C:12]([Cl:45])=[O:13])=[CH:10][CH:9]=1)[CH2:2][CH2:3][CH2:4][CH3:5]
Reactant: O=S(Cl)Cl
Reactant: CCCCCOCc1ccc(C(=O)Oc2cc(F)c(C#N)c(F)c2)cc1
Agent: CCCCCOCc1ccc(C(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: CCCCCOCc1ccc(C(=O)Cl)cc1

Procedure:
Preparation of 3,5-difluoro-4-cyanophenyl 4-(pentyloxymethyl)benzoate (in the formula (1), R=C5H11, l=1, m=1, n and o=both, 0; A1 =1,4- phenylene group, Z1 =--COO--, X=CN, and Y1 and Y2 =both, F) (Compound No. 1)) 4-(Pentyloxymethyl)benzoic acid. (1.6 g, 7.1 mmol) was mixed with thionyl chloride (1.3 g, 10.6 mmol), pyridine (0.1 ml) and toluene (3 ml), followed by reacting them at 80° C. for 2 hours, and distilling off superfluous thionyl chloride and toluene under reduced pressure, to obtain raw 4-(pentyloxymethyl)benzoyl chloride.
Reaction SMILES: [C:1]1([OH:7])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:8][C:9]12[CH2:19][C:13]3(Br)[CH2:14][C:15](Br)([CH2:17][C:11]([CH3:21])([CH2:12]3)[CH2:10]1)[CH2:16]2.Br>>[CH3:8][C:9]12[CH2:19][C:13]3([C:4]4[CH:5]=[CH:6][C:1]([OH:7])=[CH:2][CH:3]=4)[CH2:14][C:15]([C:4]4[CH:5]=[CH:6][C:1]([OH:7])=[CH:2][CH:3]=4)([CH2:17][C:11]([CH3:21])([CH2:12]3)[CH2:10]1)[CH2:16]2
Reactant: Oc1ccccc1
Reactant: CC12CC3(C)CC(Br)(C1)CC(Br)(C2)C3
Agent: Br
Product: CC12CC3(C)CC(c4ccc(O)cc4)(C1)CC(c1ccc(O)cc1)(C2)C3

Procedure:
Adamantane bisphenols can be readily made available from the corresponding dibromoderivatives and phenol according to U.S. Pat. No. 3,594,427. Thus, 112 g of 1,3-dimethyl-5,7-dibromoadamantane (III) (0.35 m) (see Example 2a) and 900 g of phenol were heated together at 170° C. for six hours. After termination of the evolution of HBr, the mixture was heated to 220° C. for a further two hour period and the excess phenol was distilled off. The reaction mixture was poured into warm water and the white precipitate was filtered, washed with warm water and dried at 80° C. under vacuum. Yield 117.8 g (97%). The product was recrystallyzed from toluene. MP: 222°-224° C.
Reaction SMILES: O.[C:2]([C:4]1[CH:11]=[CH:10]C(CN)=[CH:6][CH:5]=1)#[N:3].C1N2CN3CN(C2)CN1C3.[C:22]([OH:25])(=[O:24])[CH3:23].S(=O)(=O)(O)O>O>[C:2]([C:4]1[CH:11]=[CH:10][C:23]([C:22]([OH:25])=[O:24])=[CH:6][CH:5]=1)#[N:3]
Reactant: N#Cc1ccc(CN)cc1
Reactant: CC(=O)O
Agent: C1N2CN3CN1CN(C2)C3
Agent: O=S(=O)(O)O
Solvent: O
Product: N#Cc1ccc(C(=O)O)cc1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 84.2 %

Procedure:
20 kg of p-cyanobenzylamine crude product (p-cyanobenzylamine 92% by weight, p-xylylenediamine 8% by weight) obtained by hydrogen reduction of terephthalonitrile in the presence of sponge metal nickel catalyst was mixed with 90 kg of water while stirring at 40° C. or less and the mixture was stirred for 3 hours. The crystals which precipitated were separated by centrifugation while washing with water to obtain 20 kg of p-cyanobenzylamine hydrate (water content: 22% by weight). 20 kg of the p-cyanobenzylamine hydrate, 17.6 kg of hexamethylenetetramine, and 83 kg of acetic acid were mixed and the internal temperature was elevated to 80° C. while stirring. An aqueous sulfuric acid solution of 12.6 kg of 98% by weight sulfuric acid and 9.3kg of water was added dropwise thereto over 20 minutes. Further, the reaction mixture was stirred at 100° C. for 1 hour. After the internal temperature was decreased to 50° C., 12.6 kg of 98% by weight sulfuric acid was added. The reaction mixture was concentrated under reduced pressure to recover 75 kg of acetic acid solution. Totheresidue inthereaction vesselwas added 60 kg of water and 70 kg of toluene and stirred vigorously and thereafter left to stand. After removing the water layer, 20 kg of water was added, followed by vigorous stirring and left to stand to remove water (this operation being performed twice). The toluene was concentrated under reduced pressure to recover 48 kg of toluene. After reverting to atmospheric pressure, 54 kg of water was added and the mixture was concentrated until the distillation temperature reached a constant value (distillation of toluene was completed) to recover 21 kg of toluene and 6 kg of water. The mixture was cooled to room temperature while stirring (the mixture became an aqueous solution from which p-cyanobenzaldehyde had precipitated). 12.0 kg of acetonitrile and 8.0 kg of sodium hydrogen carbonate were mixed therewith and 125 kg of an aqueous 13.5% by weight sodium hypochlorite solution was added dropwise over 2 hours while maintaining the internal temperature of the reaction system at around 40° C. (±5° C.), and the mixture was stirred for additional 1 hour. Then, 2.1 kg of urea was added and stirred for 20 minutes and further 7.5 kg of 98% by weight sulfuric acid and 190 kg of water were added. The precipitated crystals were collected by centrifugation while washing with water, and dried to obtain 16.5 kg (yield: 94%) of p-cyanobenzoic acid. The purity was 99% or more.
Reaction SMILES: [ClH:1].Cl.Cl.[NH2:4][CH2:5][CH2:6][CH2:7][N:8]1[CH2:13][CH2:12][N:11]([CH2:14][C:15]2[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][CH:16]=2)[CH2:10][CH2:9]1.C(N(CC)CC)C.[CH2:29]([N:35]=[C:36]=[O:37])[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>O1CCCC1>[ClH:21].[ClH:1].[Cl:21][C:18]1[CH:17]=[CH:16][C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([CH2:7][CH2:6][CH2:5][NH:4][C:36]([NH:35][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[O:37])[CH2:9][CH2:10]2)=[CH:20][CH:19]=1
Reactant: NCCCN1CCN(Cc2ccc(Cl)cc2)CC1
Reactant: CCCCCCN=C=O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CCCCCCNC(=O)NCCCN1CCN(Cc2ccc(Cl)cc2)CC1
Yield: 171 %

Procedure:
The procedure described in Example 3 was followed, using 1-(3-aminopropyl)-4-(4-chlorobenzyl)piperazine trihydrochloride (3.77 g; 10 mmole), tetrahydrofuran (50 ml), triethylamine (4.2 ml; 30 mmole) and n-hexyl isocyanate (1.41 g; 10 mmole). Recrystallization from ethanol provided the title compound (4.00 g; 83% yield) as colorless crystals, m.p. 214°-215° C.
Reaction SMILES: [C:1]1([C:12]2[C:13]([NH2:22])=[CH:14][CH:15]=[C:16]3[C:21]=2[CH:20]=[CH:19][CH:18]=[CH:17]3)[C:2]([NH2:11])=[CH:3][CH:4]=[C:5]2[C:10]=1[CH:9]=[CH:8][CH:7]=[CH:6]2.[C:23]1([CH3:33])[CH:28]=[CH:27][C:26]([S:29](Cl)(=[O:31])=[O:30])=[CH:25][CH:24]=1>N1C=CC=CC=1.C(OCC)(=O)C>[C:23]1([CH3:33])[CH:28]=[CH:27][C:26]([S:29]([NH:22][C:13]2[C:12]([C:1]3[C:2]([NH:11][S:29]([C:26]4[CH:27]=[CH:28][C:23]([CH3:33])=[CH:24][CH:25]=4)(=[O:31])=[O:30])=[CH:3][CH:4]=[C:5]4[C:10]=3[CH:9]=[CH:8][CH:7]=[CH:6]4)=[C:21]3[C:16](=[CH:15][CH:14]=2)[CH:17]=[CH:18][CH:19]=[CH:20]3)(=[O:31])=[O:30])=[CH:25][CH:24]=1
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Reactant: Nc1ccc2ccccc2c1-c1c(N)ccc2ccccc12
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)Nc2ccc3ccccc3c2-c2c(NS(=O)(=O)c3ccc(C)cc3)ccc3ccccc23)cc1
Yield: 95 %

Procedure:
Under nitrogen atmosphere, to a solution in which 1,1′-binaphthyl-2,2′-diamine (0.5 mmol) was dissolved in pyridine (1 mL) was added p-toluenesulfonyl chloride (1.1 mmol) at room temperature, and the mixture was reacted for 5 to 12 hours with stirring. After completion of the reaction, the resulting red suspension was diluted with ethyl acetate, and back-extracted with 1N hydrochloric acid to remove pyridine. The resulting organic layer was dried with sodium sulfate to remove the solvent, and the residue was purified by column chromatography to obtain an objective substance as a pale yellow to white solid in more than 95% yield.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)=O.[Cl-].[CH3:14][O:15][NH3+:16].N1C=CC=CC=1>C(O)C>[CH3:14][O:15][N:16]=[C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1)[CH2:4][CH2:3][CH2:2][Cl:1]
Reactant: O=C(CCCCl)c1ccccc1
Reactant: CO[NH3+]
Agent: [Cl-]
Solvent: CCO
Solvent: c1ccncc1
Product: CON=C(CCCCl)c1ccccc1
Yield: 84.1 %

Procedure:
A mixture of 1-chloro-4-phenylbutan-4-one (1.83 g, 10 mmol), O-methylhydroxylammonium chloride (1.67 g, 20 mmol), pyridine (1.21 ml, 15 mmol), and ethanol (15 ml) was heated at reflux for 1 hour and then evaporated in vacuo. The residue was partitioned between chloroform and water, and the organic layer was dried (MgSO4) and evaporated in vacuo to give 1-chloro-4-phenylbutan-4-one O-methyloxime (1.78 g, 84%), νmax (neat) 2930, 1445, 1050, 900 cm-1 ; λmax (EtOH) 209 nm (εm 17,200), 253 nm (εm 11,100); δH (CDCl3) 7.3-7.8 (5H, m, aryl), 3.9 (3H, s, OMe), 3.5 (2H, t, H1), 2.9 (2H, t, H3), 2.0 (2H, qn, H2).