Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:14]=[CH:13][N:12]([C:15]2[NH:16][C:17]([C:21]([OH:23])=O)=[C:18]([CH3:20])[N:19]=2)[C:11](=[O:24])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:25]([NH2:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>>[CH2:25]([NH:32][C:21]([C:17]1[NH:16][C:15]([N:12]2[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)=[CH:10][C:11]2=[O:24])=[N:19][C:18]=1[CH3:20])=[O:23])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1
Reactant: Cc1nc(-n2ccc(OCc3ccccc3)cc2=O)[nH]c1C(=O)O
Reactant: NCc1ccccc1
Product: Cc1nc(-n2ccc(OCc3ccccc3)cc2=O)[nH]c1C(=O)NCc1ccccc1
Yield: 59 %

Procedure:
Following the procedure as described in Example 1, making variations only as required to use 2-(4-(benzyloxy)-2-oxopyridin-1(2H)-yl)-4-methyl-1H-imidazole-5-carboxylic acid in place of 4-methyl-2-(2-oxo-4-phenylpyridin-1(2H)-yl)thiazole-5-carboxylic acid to react with benzylamine, the title compound was obtained as a colorless solid in 59% yield: mp 183-184° C.; 1H NMR (300 MHz, CDCl3) δ 11.86 (br s, 1H), 8.42 (d, J=8.0 Hz, 1H), 7.43-7.26 (m, 10H), 6.18 (dd, J=8.0, 2.6 Hz, 1H), 6.04 (d, J=2.6 Hz, 1H), 5.05 (s, 2H), 4.61 (d, J=6.0 Hz, 2H), 2.65 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 167.4, 163.6, 163.4, 138.8, 134.6, 132.2, 129.5, 128.8, 128.7, 128.6, 127.8, 127.8, 127.3, 126.9, 103.5, 98.4, 70.7, 42.7, 11.0; MS (ES+) m/z 415.2 (M+1).
Reaction SMILES: [OH-].[NH4+:2].[CH3:3][C:4]1[CH:8]=[CH:7][O:6][C:5]=1[C:9](Cl)=[O:10]>>[CH3:3][C:4]1[CH:8]=[CH:7][O:6][C:5]=1[C:9]([NH2:2])=[O:10]
Reactant: [NH4+]
Reactant: Cc1ccoc1C(=O)Cl
Agent: [OH-]
Product: Cc1ccoc1C(N)=O

Procedure:
To a stirred flask containing excess concentrated ammonium hydroxide was added gradually 50 g of 3-methyl-2-furoyl chloride. The resulting mixture was extracted with dichloromethane. The extracts were dried, then evaporated to provide solid 3-methylfuran-2-carboxamide.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:12](=[O:25])(=[O:24])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)=[C:6]([CH2:8][C:9]([OH:11])=O)[CH:7]=1.[CH2:26]([NH:30][CH3:31])[CH2:27][CH2:28][CH3:29].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.O>CN(C=O)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([S:12](=[O:24])(=[O:25])[NH:13][C:14]2[CH:15]=[CH:16][C:17]3[CH2:21][O:20][B:19]([OH:22])[C:18]=3[CH:23]=2)=[C:6]([CH2:8][C:9]([N:30]([CH2:26][CH2:27][CH2:28][CH3:29])[CH3:31])=[O:11])[CH:7]=1
Reactant: CCCCNC
Reactant: Nc1ccc(S(=O)(=O)Nc2ccc3c(c2)B(O)OC3)c(CC(=O)O)c1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: O
Solvent: CN(C)C=O
Product: CCCCN(C)C(=O)Cc1cc(N)ccc1S(=O)(=O)Nc1ccc2c(c1)B(O)OC2
Reaction time: 16 h
Yield: 26.7 %

Procedure:
To a stirred solution of 2-(5-amino-2-(N-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-6-yl)sulfamoyl)phenyl)acetic acid (360 mg, 1 mmol) and n-butylmethylamine (0.6 mL, 6 mmol) in 10 mL of DMF was added PyBOP (780 mg, 1.5 mmol) and TEA (0.5 mL, 3.56 mmol). The reaction mixture was stirred for 16 hours. After water was added, the reaction mixture was extracted with ethyl acetate and washed with water, 1N HCl and brine. The organic layer was dried over Na2SO4 and concentrated. The crude residue was first purified by prep HPLC (SunFire Prep C18 OBD 5 uM 30×50 mm column) to give the desired product as a yellow solid (115 mg, yield 27%). MS calcd for (C20H26BN3O5S): 431.2. MS found (ESI negative): (M−H)−=430.1. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 9.80 (s, 1H), 9.17 (bs, 1H), 7.45 (m, 2H), 7.22 (d, J=8 Hz, 1H), 7.11 (d, J=8, 2 Hz, 1H), 6.37 (d, J=8.4 Hz, 1H), 6.32 (s, 1H), 5.94 (bs, 2H), 4.87 (s, 2H), 3.77 (s, 2H), 3.15 (m, 2H), 2.85 (s, 3H), 1.39 (m, 2H), 1.30 (m, 2H), 0.87 (t, J=7.2 Hz, 3H).
Reaction SMILES: [Br:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:4]=2[C:3]=1[C:11]([OH:13])=O.[NH2:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=1[OH:22]>S(Cl)(Cl)=O>[Br:1][C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:4]=2[C:3]=1[C:11]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][C:16]=1[OH:22])=[O:13]
Reactant: O=C(O)c1c(Br)sc2c1CCCC2
Reactant: Cc1ccc(N)c(O)c1
Solvent: O=S(Cl)Cl
Product: Cc1ccc(NC(=O)c2c(Br)sc3c2CCCC3)c(O)c1
Yield: 68.9 %

Procedure:
In the same manner as in Starting Material Synthesis Example 60 and using 2-bromo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylic acid (6 g), thionyl chloride (30 ml), 2-amino-5-methylphenol (3.14 g), 2-bromo-4,5,6,7-tetrahydro-N-(2-hydroxy-4-methylphenyl)-benzo[b]thiophene-3-carboxamide (5.8 g) was obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[CH:5]2.[H-].[Na+].[C:13]1([S:19](Cl)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C([O-])(O)=O.[Na+]>CN(C=O)C>[C:13]1([S:19]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([Cl:1])=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)(=[O:21])=[O:20])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: Clc1ccc2[nH]ccc2c1
Reactant: O=S(=O)(Cl)c1ccccc1
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: O=S(=O)(c1ccccc1)n1ccc2cc(Cl)ccc21
Temperature: 25 °C
Reaction time: 1 h
Yield: 77.9 %

Procedure:
To a stirred solution of 5-chloroindole (20 g, 131.93 mmol, 1 eq.) in dry DMF (250 mL) at 0° C., was added NaH (5.38 g, 134.57 mmol, 1.02 eq.). After stirring at room temperature for 1 h, benzenesulfonyl chloride (23.77 g, 134.57 mmol, 1.02 eq.) was added slowly. The reaction mixture was stirred for additional 1 h, then poured into 1 L of 5% aq. NaHCO3 and extracted with EtOAc (×3). The organic layers were combined, washed with H2O (×3), brine (×3), dried over (Na2SO4), filtered, and the filtrate was concentrated. The material was purified by flash chromatography to yield 30 g of 1-phenylsulfonyl-5-chloroindole as colorless crystals.
Reaction SMILES: [CH2:1]([N:8]=[C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H][H]>CO>[CH2:1]([NH:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(=NCc1ccccc1)c1ccccc1
Reactant: [H][H]
Solvent: CO
Product: CC(NCc1ccccc1)c1ccccc1
Reaction time: 24 h

Procedure:
N-Benzyl-1-phenylethanimine (0.11 g, 0.5 mmol) and each metal complex (0.005 mmol) were weighed in a Pyrex (registered trade name) test tube for autoclaving, the tube was set in a 50-mL autoclave together with a stirrer in the tube, and the atmosphere in the autoclave was substituted with nitrogen. The mixture was added with 2 mL of methanol and EtsN (14 μL, 0.1 mmol), the atmosphere in the autoclave was sufficiently substituted with hydrogen, and then pressurized with 5.0 MPa of hydrogen, and the reaction was allowed at 40° C. for 24 hours. After the reaction, the reaction mixture was added with 0.02 g of activated carbon and stirred for 30 minutes, and after the activated carbon was removed, the reaction mixture was concentrated in an evaporator to quantitatively obtain optically active N-benzyl-1-phenylethylamine.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=O)([O-:3])=[O:2].[CH:12](=[O:14])[CH3:13]>>[N+:1]([C:4]1[CH:5]=[C:6]([CH:9]=[CH:10][CH:11]=1)[CH:7]=[CH:13][CH:12]=[O:14])([O-:3])=[O:2]
Reactant: CC=O
Reactant: O=Cc1cccc([N+](=O)[O-])c1
Product: O=CC=Cc1cccc([N+](=O)[O-])c1

Procedure:
3-nitro cinnamaldehyde was prepared by Claisen-Schmidt condensation of 3-nitrobenzaldehyde with acetaldehyde as follows.
Reaction SMILES: C(O)C.[OH:4][CH2:5][CH2:6][NH:7][CH2:8][CH2:9][N:10]1[CH2:15][CH2:14][N:13]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)[CH2:12][CH2:11]1.Cl[C:26]1[N:31]([CH3:32])[C:30](=[O:33])[N:29]([CH3:34])[C:28](=[O:35])[CH:27]=1>C(N(CC)CC)C>[CH3:32][N:31]1[C:26]([N:7]([CH2:8][CH2:9][N:10]2[CH2:11][CH2:12][N:13]([C:16]3[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=3)[CH2:14][CH2:15]2)[CH2:6][CH2:5][OH:4])=[CH:27][C:28](=[O:35])[N:29]([CH3:34])[C:30]1=[O:33]
Reactant: O=[N+]([O-])c1ccc(N2CCN(CCNCCO)CC2)cc1
Reactant: Cn1c(Cl)cc(=O)n(C)c1=O
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cn1c(N(CCO)CCN2CCN(c3ccc([N+](=O)[O-])cc3)CC2)cc(=O)n(C)c1=O

Procedure:
To 10 ml of ethanol were added 1.0 g of the thus obtained compound 75, 0.52 g of 6-chloro-1,3-dimethyl-2,4(1H,3H)-pyrimidinedione and 2 ml of triethylamine as starting materials, and the resulting mixture was treated in the same procedure as in Example 39-(2) to obtain 0.73 g of 1,3-dimethyl-6-{N-(2-hydroxyethyl)-2-[4-(4-nitrophenyl)piperazin-1-yl]ethylamino}-2,4(1H,3H)-pyrimidinedione.
Reaction SMILES: Br[C:2]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[CH:6][C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[N:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1B(O)O>C1(C)C=CC=CC=1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[C:2]1[C:7]([C:8]([NH:10][CH3:11])=[O:9])=[CH:6][C:5]([N:12]2[CH2:17][CH2:16][N:15]([CH3:18])[CH2:14][CH2:13]2)=[N:4][CH:3]=1
Reactant: OB(O)c1ccccc1Cl
Reactant: CNC(=O)c1cc(N2CCN(C)CC2)ncc1Br
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: Cc1ccccc1
Product: CNC(=O)c1cc(N2CCN(C)CC2)ncc1-c1ccccc1Cl
Temperature: 80 °C
Yield: 63.6 %

Procedure:
To a suspension of 1.20 g (3.83 mmol) 5-bromo-N-methyl-2-(4-methyl-piperazin-1-yl)-isonicotinamide in 15 ml toluene were added successively 0.135 g tetrakis(triphenylphosphine)palladium(0), 4 ml 2 M sodium carbonate solution in water and 0.72 g (4.6 mmol) o-chlorphenylboronic acid. The mixture was heated under argon at 80° C. for 18 h. The aqueous layer was separated and washed with toluene. The combined organic layers were washed with brine, dried (magnesium sulfate) and evaporated. Chromatography of the residue afforded 0.84 g (63%) of the title compound as a pale brown foam.
Reaction SMILES: [OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])(C)C)=[O:16])[CH2:3]1.CO.Cl>C(Cl)(Cl)Cl>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([OH:14])=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][CH2:18][C:21]2[CH:3]=[CH:2][CH:7]=[CH:6][CH:5]=2)=[O:16])[CH2:3]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2ccc(O)cc2)C(O)C1
Agent: Cl
Solvent: CO
Solvent: ClC(Cl)Cl
Product: O=C(OCc1ccccc1)N1CCC(c2ccc(O)cc2)C(O)C1
Temperature: 60 °C
Reaction time: 20 h

Procedure:
The mixture of 6.0 g of tert-butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate, 120 ml of methanol, 40 ml of chloroform and 20 ml of 2M HCl is stirred at 60° C. over 20 hours. The reaction mixture is cooled and the organic solvent is evaporated off. The resulting aqueous solution is admixed with stirring with 80 ml of saturated sodium hydrogencarbonate solution and 80 ml of ethyl acetate. The biphasic mixture is cooled to 0° C. and admixed slowly with 3.30 ml of benzyl chloroformate and stirred over a further 2 hours. The reaction mixture is extracted with ethyl acetate-tetrahydrofuran. The organic phases are concentrated by evaporation and the title compound is obtained as a white solid from the residue by means of crystallization (ethyl acetate-heptane). Rt=5.72.
Reaction SMILES: Cl.[CH2:2]([O:4][C:5](=[O:23])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][CH:13]([C:20]([OH:22])=[O:21])[C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH:7]=1)[CH3:3].C1C=CC2N(O)N=NC=2C=1.[N:34]12[CH2:41][CH2:40][CH:37]([CH2:38][CH2:39]1)[C@@H:36](O)[CH2:35]2.CCN(C(C)C)C(C)C>C1COCC1>[CH2:2]([O:4][C:5](=[O:23])[C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([NH:12][CH:13]([C:20]([O:22][C@@H:36]2[CH:37]3[CH2:40][CH2:41][N:34]([CH2:39][CH2:38]3)[CH2:35]2)=[O:21])[C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH:7]=1)[CH3:3]
Reactant: O[C@H]1CN2CCC1CC2
Reactant: CCOC(=O)c1cccc(NC(C(=O)O)c2ccccc2)c1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: CCOC(=O)c1cccc(NC(C(=O)O[C@H]2CN3CCC2CC3)c2ccccc2)c1
Reaction time: 8 h
Yield: 78.5 %

Procedure:
3-[(Carboxy-phenyl-methyl)-amino]-benzoic acid ethyl ester hydrochloride (I66) (161 mg, 0.48 mmol), 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate(V) (218 mg, 0.57 mmol), and HOBT (88 mg, 0.57 mmol) are dissolved in dry THF (10 mL). (R)-Quinuclidin-3-ol (61.0 mg, 0.48 mmol) and DIPEA (0.17 mL, 0.96 mmol) are added and the mixture is stirred under inert atmosphere overnight. THF is evaporated and the crude residue is dissolved in EtOAc and washed with sat. NaHCO3, water and brine. The recovered organic layer is dried (Na2SO4), filtered and evaporated. The crude is purified by flash chromatography (DCM/MeOH=95/5) to afford the title compound as a yellow oil (154 mg, 79% yield, mixture of diastereoisomers).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[C:4]([CH3:9])[C:3]=1[CH2:10][C:11](Cl)=[O:12].C(=O)([O-])[O-].[K+].[K+].[NH2:20][C:21]1([C:30]#[N:31])[CH2:26][CH2:25][N:24]([O:27][CH2:28][CH3:29])[CH2:23][CH2:22]1>C(#N)C>[C:30]([C:21]1([NH:20][C:11](=[O:12])[CH2:10][C:3]2[C:2]([CH3:1])=[CH:7][C:6]([CH3:8])=[CH:5][C:4]=2[CH3:9])[CH2:26][CH2:25][N:24]([O:27][CH2:28][CH3:29])[CH2:23][CH2:22]1)#[N:31]
Reactant: Cc1cc(C)c(CC(=O)Cl)c(C)c1
Reactant: CCON1CCC(N)(C#N)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: CCON1CCC(C#N)(NC(=O)Cc2c(C)cc(C)cc2C)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 89.5 %

Procedure:
3.0 g of (2,4,6-trimethyl-phenyl)-acetyl chloride and 10 g of potassium carbonate in 90 ml of acetonitrile were treated at 0° C. with a solution of 3.6 g of 4-amino-1-ethoxy-piperidine-4-carbonitrile in 30 ml of acetonitrile. After stirring for 18 hours at room temperature the reaction mixture was poured into 100 ml of ice water and extracted with ethyl acetate. The organic phase was washed with brine and concentrated. Chromatography (heptane/ethyl acetate 5:1) yielded 4.5 g of N-(4-cyano-1-ethoxy-piperidin-4-yl)-2-(2,4,6-trimethyl-phenyl)-acetamide as a solid, mp: 194-195° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].CO[CH:14]1[CH2:18][CH2:17][CH:16](OC)O1>C(O)(=O)C>[N+:8]([C:6]1[CH:5]=[CH:4][C:3]([OH:11])=[C:2]([N:1]2[CH:14]=[CH:18][CH:17]=[CH:16]2)[CH:7]=1)([O-:10])=[O:9]
Reactant: Nc1cc([N+](=O)[O-])ccc1O
Reactant: COC1CCC(OC)O1
Solvent: CC(=O)O
Product: O=[N+]([O-])c1ccc(O)c(-n2cccc2)c1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 58.3 %

Procedure:
2-Amino-4-nitrophenol (5 g, 32.0 mmol) and 2,5-dimethoxytetrahydrofuran (5.03 ml, 38.4 mmol) were dissolved in glacial acetic acid (100 ml), followed by stirring at the reflux temperature for 10 min. After subsequent cooling to room temperature, the solvent was evaporated under vacuum and the residue was neutralized with an aqueous solution of sodium carbonate, followed by three extractions with ethyl acetate. The organic solvent layers were combined, dried with magnesium sulfate and the solvent was evaporated; thereafter, the residue was purified by being subjected to column chromatography on silica gel using a 2:1 solvent system of n-hexane and ethyl acetate as an eluent; the fractions containing the product were collected and the solvent was evaporated to yield the end compound 4-nitro-2-(1H-pyrrol-1-yl)phenol (3.81 g).
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H][H]>C1CCCCC1>[CH:1]1([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: c1ccccc1
Solvent: C1CCCCC1
Product: c1ccc(C2CCCCC2)cc1

Procedure:
FIG. 2 is a diagram of a reactive distillation unit for conducting the dealkylation step of the process shown in FIG. 1. The embodiment shown in FIG. 2 includes a vertical distillation tower 111 which is provided with a cracking zone 112 located near the base of the tower, which also receives the optional benzene and hydrogen feeds. The product of the hydroalkylation reactor, after removal of the unreacted benzene, is introduced by line 113 into the tower mid-way along the tower 111. On entering the distillation tower 111, the hydroalkylation product is separated into a C18 fraction, which descends through the tower to the cracking zone 112, and a C12 fraction which leaves the tower as overhead 114. The C18 fraction is dealkylated in the cracking zone to produce monocyclohexylbenzene product cyclohexene, and/or cyclohexane, which exit the tower 111 as part of the overhead 114. The overhead is then passed through a cooler 115 to remove any unreacted PCHB, which is recycled to the tower via line 116 and any unreacted hydrogen, which is vented from the cooler via line 117. The remaining overhead, which is composed mainly of cyclohexylbenzene, cyclohexene, and/or cyclohexane, is then passed to a distillation system (not shown) to separate the C6 and C12 fractions. Any unreacted C18 and heavier compounds (i.e., heavies) exit through the bottoms stream of the column.
Reaction SMILES: [C-:1]#[N:2].[K+].Cl[CH2:5][CH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[CH2:10]2>CS(C)=O>[C:1]([CH2:5][CH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11](=[O:16])[CH2:10]2)#[N:2]
Reactant: [C-]#N
Reactant: O=C1Cc2cc(CCCl)ccc2N1
Agent: [K+]
Solvent: CS(C)=O
Product: N#CCCc1ccc2c(c1)CC(=O)N2
Temperature: 90 °C
Yield: 42 %

Procedure:
Potassium cyanide (2.0 g) was added to 15 mL of dimethylsulfoxide and heated to 90° C. 5-Chloroethyl-2-oxindole (3.0 g) dissolved in 5 mL dimethyl sulfoxide was added slowly with stirring, and the reaction heated to 150° C. for 2 hours. The mixture was cooled, poured into ice water and the precipitate collected by vacuum filtration, washed with water, dried and then chromatographed on silica gel (5% methanol in chloroform) to give 1.2 g (42% yield) of the title compound.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[CH2:7][C:6](=[O:8])[CH2:5][C:4](=[O:9])[CH:3]1[F:10].N1C=CC=CC=1.[N+:18]([C:21]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:22]=1[C:23](Cl)=[O:24])([O-:20])=[O:19]>C(Cl)Cl>[CH3:1][C:2]1([CH3:11])[CH:3]([F:10])[C:4](=[O:9])[CH:5]=[C:6]([O:8][C:23](=[O:24])[C:22]2[CH:26]=[CH:27][C:28]([C:30]([F:33])([F:32])[F:31])=[CH:29][C:21]=2[N+:18]([O-:20])=[O:19])[CH2:7]1
Reactant: O=C(Cl)c1ccc(C(F)(F)F)cc1[N+](=O)[O-]
Reactant: CC1(C)CC(=O)CC(=O)C1F
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC1(C)CC(OC(=O)c2ccc(C(F)(F)F)cc2[N+](=O)[O-])=CC(=O)C1F
Temperature: 25 °C
Reaction time: 24 h

Procedure:
5,5-Dimethyl-4-fluoro-1,3-cyclohexanedione [0.5 grams (g), 0.0032 mole, prepared according to the teaching of Liebigs Ann. Chem., 679, 9 (1964)] and 0.25 g (0.0032 mole) pyridine were dissolved in 20 milliliters (ml) methylene chloride at room temperature. 2-Nitro-4-trifluoromethylbenzoyl chloride (1.0 g, 0.0039 mole) dissolved in 20 ml methylene chloride was slowly added with cooling. The reaction mixture was stirred at room temperature for 24 hours and then washed two times with water, one time with saturated sodium bicarbonate aqueous solution and one with with water. The aqueous phases were discarded and the organic phase dried with MgSO4 and then evaporated to yield the intermediate enol ester, 5,5-dimethyl-6-fluoro-3-(2-nitro-4-trifluoromethylbenzoyloxy)cyclohex-2-enone. The 5,5-dimethyl-6-fluoro-3-(2-nitro-4-trifluoromethylbenzoyloxy)cyclohex-2-enone was dissolved in 30 ml acetonitrile and triethylamine (0.7 g, 0.007 mole) which was added all at once, followed by acetonecyanohydrin (0.05 g, 0.0006 mole). The solution was stirred for 24 hours. The solvent was evaporated and the residue washed with diethyl ether to yield the product.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7](=[O:12])[CH2:6][CH:5]2[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[BH4-].[Na+].C(O)(=O)C>CO>[OH:12][CH2:7][CH2:6][CH:5]([C:4]1[CH:3]=[C:2]([CH3:1])[CH:11]=[CH:10][C:9]=1[OH:8])[C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=1
Reactant: Cc1ccc2c(c1)C(c1ccccc1)CC(=O)O2
Agent: [BH4-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: Cc1ccc(O)c(C(CCO)c2ccccc2)c1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
6-methyl-4-phenyl-chroman-2-one, 250 gins was stirred in 1.25 liters methanol at room temperature. Sodium borohydride 70 gms was added slowly, whilst maintaining the temperature at room temperature. The reaction mixture was stirred for 18 hours. After completion of reaction, the pH of the reaction mass was adjusted to pH 5 using acetic acid. The reaction mixture was concentrated under vacuum and 2 liters of water were added. The reaction mass was stirred for 30 minutes and the solids filtered. The solids were dried at 55° C. in a hot air oven for 20 hours. Weight 248 gms.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[C:6]([C:7]([OH:9])=O)[C:5]([OH:11])=[CH:4][CH:3]=1.[F:12][C:13]([F:22])([F:21])[C:14]1[CH:15]=[C:16]([CH:18]=[CH:19][CH:20]=1)[NH2:17]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([CH:10]=1)[C:7]([NH:17][C:16]1[CH:18]=[CH:19][CH:20]=[C:14]([C:13]([F:12])([F:21])[F:22])[CH:15]=1)=[O:9]
Reactant: O=C(O)c1cc(Br)ccc1O
Reactant: Nc1cccc(C(F)(F)F)c1
Product: O=C(Nc1cccc(C(F)(F)F)c1)c1cc(Br)ccc1O
Yield: 50.3 %

Procedure:
Using 5-bromosalicylic acid and 3-(trifluoromethyl)aniline as the raw materials, the same operation as the example 16 gave the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([CH:9]=[O:10])[CH:6]=[CH:5][C:4]=1[OH:11].Br[CH2:13][CH2:14][CH2:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(=O)([O-])[O-].[K+].[K+].CC(=O)CC>O>[C:17]1([CH2:16][CH2:15][CH2:14][CH2:13][O:11][C:4]2[CH:5]=[CH:6][C:7]([CH:9]=[O:10])=[CH:8][C:3]=2[O:2][CH3:1])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: BrCCCCc1ccccc1
Reactant: COc1cc(C=O)ccc1O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: O
Product: COc1cc(C=O)ccc1OCCCCc1ccccc1
Yield: 37.5 %

Procedure:
A mixture of 860 mg of vaniline, 1.00 g of 4-bromobutylbenzene, 1.00 g of potassium carbonate and 8 ml of 2-butanone was heated under reflux for 3 hours. The reaction mixture was poured into water and the product was extracted with ether. The ethereal layer was washed with water, dried and concentrated. The obtained residue was applied to silica gel column chromatography and eluted with toluene to obtain 500 mg of 4-(4-phenylbutoxy)-3-methoxybenzaldehyde.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH:3]=1.[F-:22].[Cs+]>[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].CS(C)=O>[F:22][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[C:4]([C:14]2[CH:21]=[CH:20][C:17]([C:18]#[N:19])=[CH:16][CH:15]=2)[CH:3]=1
Reactant: COc1ccc2nc(-c3ccc(C#N)cc3)cc(Cl)c2c1
Reactant: [F-]
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [Br-]
Agent: [Cs+]
Solvent: CS(C)=O
Product: COc1ccc2nc(-c3ccc(C#N)cc3)cc(F)c2c1
Temperature: 150 °C
Yield: 31.7 %

Procedure:
A mixture of 4-(4-chloro-6-methoxyquinolin-2-yl)benzonitrile (Seem Example 11, step 1) (1 g, 3.4 mmol), CsF (5.2 g, 34 mmol), and n-Bu4NBr (109 mg, 0.34 mmol) in DMSO (10 mL) was heated to 150° C. for 2 h. An aqueous/EtOAC workup was followed by purification by column chromatography (PE/EA=10/1) to afford desired product (300 mg, 31.7%).
Reaction SMILES: [Cl:1][C:2]1[N:3]=[C:4]([C:9]([OH:11])=O)[NH:5][C:6]=1[CH2:7][CH3:8].S(Cl)(Cl)=O.[NH2:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]2[O:24][C:25]([CH2:33][CH3:34])=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=2)=[CH:19][CH:18]=1>N1C=CC=CC=1>[Cl:1][C:2]1[N:3]=[C:4]([C:9]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([C:23]3[O:24][C:25]([CH2:33][CH3:34])=[C:26]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[N:27]=3)=[CH:21][CH:22]=2)=[O:11])[NH:5][C:6]=1[CH2:7][CH3:8]
Reactant: CCOC(=O)c1nc(-c2ccc(N)cc2)oc1CC
Reactant: CCc1[nH]c(C(=O)O)nc1Cl
Solvent: c1ccncc1
Solvent: O=S(Cl)Cl
Product: CCOC(=O)c1nc(-c2ccc(NC(=O)c3nc(Cl)c(CC)[nH]3)cc2)oc1CC
Yield: 71.7 %

Procedure:
The same operation as in Example (91c) was performed using 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid (0.21 g, 1.2 mmol), thionyl chloride (5 mL), ethyl 2-(4-aminophenyl)-5-ethyl-1,3-oxazole-4-carboxylate obtained in Example (99b) (0.2 g, 0.77 mmol) and pyridine (5 mL), to obtain 0.23 g of the title compound as a light pink solid (72%).