Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[S:3]([O:6]S(C(F)(F)F)(=O)=O)(=[O:5])=[O:4].[CH:16]([C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][C:19]=1O)=[O:17].C(N(CC)C(C)C)(C)C>ClCCl>[F:1][C:2]([F:15])([F:14])[S:3]([O:6][C:25]1[CH:24]=[C:21]([C:22]#[N:23])[CH:20]=[CH:19][C:18]=1[CH:16]=[O:17])(=[O:5])=[O:4]
Reactant: N#Cc1ccc(C=O)c(O)c1
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: N#Cc1ccc(C=O)c(OS(=O)(=O)C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
2.4 ml (14.27 mmol) of trifluoromethanesulfonic anhydride are added dropwise to a solution of 2 g (13.59 mmol) of 4-formyl-3-hydroxybenzonitrile and 2.5 ml (14.27 mmol) of N,N-diisopropyl-ethylamine in 37 ml of anhydrous dichloromethane at 0° C. under an argon atmosphere. The reaction mixture is stirred at RT for 1 h, then diluted with 70 ml of dichloromethane and washed successively with 1 M hydrochloric acid, saturated sodium bicarbonate solution and saturated sodium chloride solution. The organic solution is dried over magnesium sulfate and concentrated. The residue is purified by column chromatography on silica gel (mobile phase: cyclohexane/ethyl acetate 7:1). 2.36 g (62% of theory) of the title compound are obtained as a white solid.
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.Br[CH2:10][CH:11]1[CH2:13][O:12]1>>[I:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][CH2:10][CH:11]2[CH2:13][O:12]2)=[CH:4][CH:3]=1
Reactant: BrCC1CO1
Reactant: Oc1ccc(I)cc1
Product: Ic1ccc(OCC2CO2)cc1
Yield: 89 %

Procedure:
Alkylation of 4-iodophenol with 2-(bromomethyl)oxirane (76) as in Example 2A for 52 h, followed by chromatography of the product on silica gel, eluting with 0-10% CH2Cl2/petroleum ether (foreruns) and then with 20-25% CH2Cl2/petroleum ether, gave 2-[(4-iodophenoxy)methyl]oxirane (79) (reported by Apparu et al., 2000 using glycidyl tosylate) (89%) as a white solid: mp (CH2Cl2/petroleum ether) 67-68° C.; 1H NMR (CDCl3) δ 7.56 (dt, J=9.0, 2.7 Hz, 2H), 6.70 (dt, J=9.0, 2.7 Hz, 2H), 4.20 (dd, J=11.1, 3.1 Hz, 1H), 3.92 (dd, J=11.1, 5.7 Hz, 1H), 3.33 (m, 1H), 2.90 (dd, J=4.8, 4.3 Hz, 1H), 2.74 (dd, J=4.9, 2.6 Hz, 1H).
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][CH:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH2:11][C:10]([CH3:23])([CH3:22])[C:9]=2/[CH:24]=[CH:25]/[CH:26]=[O:27])=[CH:4][C:3]=1[CH3:28].[Li+].CC([N-]C(C)C)C.[C:37]([O:43][CH3:44])(=[O:42])[CH2:38][C:39]([CH3:41])=[O:40]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:13][CH:12]([O:14][Si:15]([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:16])[CH3:17])[CH2:11][C:10]([CH3:22])([CH3:23])[C:9]=2/[CH:24]=[CH:25]/[CH:26]([OH:27])[CH2:41][C:39](=[O:40])[CH2:38][C:37]([O:43][CH3:44])=[O:42])=[CH:4][C:3]=1[CH3:28]
Reactant: COC(=O)CC(C)=O
Reactant: Cc1cc(C2=C(/C=C/C=O)C(C)(C)CC(O[Si](C)(C)C(C)(C)C)C2)ccc1F
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COC(=O)CC(=O)CC(O)/C=C/C1=C(c2ccc(F)c(C)c2)CC(O[Si](C)(C)C(C)(C)C)CC1(C)C

Procedure:
In a manner similiar to Scheme I, 19 (13.45 g, 33.4 mmol) was treated with LDA-derived dianion of methyl acetoacetate (40.1 mmol) in THF and, after workup and purification by HPLC. using 4:1 hexanes:EtOAc as eluent provided 7.8 g of an orange color oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([OH:12])=O)[CH:5]=[CH:6][C:7]=1[Cl:8].C1N=CN(C(N2C=NC=C2)=O)C=1.Cl.[NH2:26][CH2:27][C:28]1[CH:29]=[C:30]2[C:34](=[CH:35][CH:36]=1)[C:33](=[O:37])[N:32]([CH:38]1[CH2:43][CH2:42][C:41](=[O:44])[NH:40][C:39]1=[O:45])[CH2:31]2.O>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:26][CH2:27][C:28]2[CH:29]=[C:30]3[C:34](=[CH:35][CH:36]=2)[C:33](=[O:37])[N:32]([CH:38]2[CH2:43][CH2:42][C:41](=[O:44])[NH:40][C:39]2=[O:45])[CH2:31]3)=[O:12])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: NCc1ccc2c(c1)CN(C1CCC(=O)NC1=O)C2=O
Reactant: O=C(O)Cc1ccc(Cl)c(Cl)c1
Agent: Cl
Agent: O=C(n1ccnc1)n1ccnc1
Solvent: CN(C)C=O
Solvent: O
Product: O=C(Cc1ccc(Cl)c(Cl)c1)NCc1ccc2c(c1)CN(C1CCC(=O)NC1=O)C2=O
Temperature: 70 °C
Reaction time: 4 h
Yield: 34.8 %

Procedure:
A mixture of 3,4-dichlorophenyl-acetic acid (0.31 g, 1.5 mmol) and CDI (0.26 g, 1.6 mmol) in DMF (20 mL) was stirred at 70° C. under N2. After 4 h, 3-(5-(aminomethyl)-1-oxoisoindolin-2-yl)piperidine-2,6-dione hydrochloride (0.47 g, 1.5 mmol) was added. The mixture was cooled to 40° C. and was stirred at this temperature for an additional 16 h. Water (30 mL) was added resulting in precipitation of the product. The solid precipitate was filtered, washed with water (50 mL) and dried in vacuo providing 2-(3,4-dichloro-phenyl)-N-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-5-ylmethyl]-acetamide as a yellow solid (0.24 g, 34% yield); mp 191-193° C.; HPLC, Waters Symmetry C18, 5 μm, 3.9×150 mm, 1 ml/min, 240 nm, 40/60 CH3CN/0.1% H3PO4. 4.17 (98.19%); 1H NMR (DMSO-d6) δ 1.98-2.02 (m, 1H), 2.32-2.45 (m, 1H), 2.57-2.73 (m, 1H), 2.86-2.98 (m, 1H), 3.54 (s, 2H), 4.45-5.14 (m, 4H), 5.11 (dd, 1H, J=13.2, J=5.1), 7.24 (dd, 1H, J=8.4, J=6.3), 7.29-7.47 (m, 2H), 7.48-7.59 (m, 2H), 7.67 (d, 1H, J=7.8), 8.72 (t, 1H, J=5.7), 10.99 (s, 1H); 13C NMR (DMSO-d6) δ 22.5, 31.2, 41.0, 42.3, 47.1, 51.6, 122.1, 123.0, 127.1, 129.1, 129.5, 130.3, 130.4, 130.6, 131.1, 137.3, 142.3, 143.6, 168.0, 169.4, 170.9, 172.8; LCMS: MH=461, 463; Anal. Calcd for C22H19Cl2N3O4+0.5H2O: C, 56.30; H, 4.30; N, 8.95. Found: C, 56.19; H, 3.91; N, 8.56.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[CH:10][NH:11][CH:12]=2)=[CH:4][CH:3]=1.[CH:13]1([N+:19]#[C-:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1>Cl[Cu]>[CH:13]1([NH:19][CH:20]=[N:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:9]=[CH:10][NH:11][CH:12]=3)=[CH:6][CH:7]=2)[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1
Reactant: [C-]#[N+]C1CCCCC1
Reactant: Nc1ccc(-c2c[nH]cn2)cc1
Agent: Cl[Cu]
Product: C(=Nc1ccc(-c2c[nH]cn2)cc1)NC1CCCCC1
Temperature: 150 °C

Procedure:
A mixture of 1.59 gm of 4-(p-aminophenyl)-1-H-imidazole, 1.2 gm of cyclohexyl isonitrile, and 0.99 gm of CuCl was heated at 150° C. for three hours. The thick reaction mixture was extracted with methanol. The methanol solution, after treatment with charcoal, was evaporated to dryness and extracted with ethyl acetate and 10% hydrochloric acid. The acid solution was adjusted to pH 7.5 with 17% Na2CO3 and extracted with ethyl acetate. The organic solution was evaporated to dryness. The substance remaining after recrystallization from acetone comprised 0.25 gm of the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][CH:7]2[CH2:11][CH2:10][C:9]3([CH2:16][O:15]C(C)(C)[O:13][CH2:12]3)[C:8]2([CH2:20][N:21]2[CH:25]=[N:24][CH:23]=[N:22]2)[OH:19])=[CH:4][CH:3]=1.N1C=CC=C1>CO.Cl>[Cl:1][C:2]1[CH:27]=[CH:26][C:5]([CH2:6][CH:7]2[C:8]([CH2:20][N:21]3[CH:25]=[N:24][CH:23]=[N:22]3)([OH:19])[C:9]([CH2:12][OH:13])([CH2:16][OH:15])[CH2:10][CH2:11]2)=[CH:4][CH:3]=1
Reactant: CC1(C)OCC2(CCC(Cc3ccc(Cl)cc3)C2(O)Cn2cncn2)CO1
Agent: Cl
Solvent: c1cc[nH]c1
Solvent: CO
Product: OCC1(CO)CCC(Cc2ccc(Cl)cc2)C1(O)Cn1cncn1
Temperature: 25 °C
Reaction time: 23 h

Procedure:
(cis, trans mixture)-2-(4-chlorobenzyl)-8,8-dimethyl-1-[1,2,4]triazole-1-ylmethyl7,9-dioxaspiro[4,5]decane-1-ol (azole derivative (V′), R6═CH3, R7═CH3, Xm=4-Cl, A=N) (359 mg) was dissolved in a 10% hydrogen chloride methanol solution, and was stirred at a room temperature for 23 hours. After the reaction, a solvent was distilled off, and water was added to a residue. A 2 mol/L sodium hydroxide aqueous solution was added to this suspension, and the resultant mixture was stirred at a room temperature for 15 minutes. The mixture was filtered to obtain a crystal, and the crystal was dried in vacuum to obtain 271.1 mg of (1SR,5RS)-5-(4-chlorobenzyl)-2,2-bishydroxymethyl-1-[1,2,4]triazole-1-ylmethylcyclopentanol(azole derivative (IV′), Xm=4-Cl, A=N).
Reaction SMILES: [Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[CH2:4][O:5][C:6]1[CH:15]=[C:14]([C:16]([OH:18])=O)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH3:19])[CH:12]=2)[N:7]=1.[NH2:24][C:25]1[S:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=1.Cl.CN(C)CCCN=C=NCC>CN(C)C=O.CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:23]=[CH:22][CH:21]=[CH:20][C:3]=1[CH2:4][O:5][C:6]1[CH:15]=[C:14]([C:16](=[O:18])[NH:24][C:25]2[S:26][C:27]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[CH:28][N:29]=2)[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([CH3:19])[CH:12]=2)[N:7]=1
Reactant: CCOC(=O)c1cnc(N)s1
Reactant: Cc1ccc2nc(OCc3ccccc3Cl)cc(C(=O)O)c2c1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCOC(=O)c1cnc(NC(=O)c2cc(OCc3ccccc3Cl)nc3ccc(C)cc23)s1
Temperature: 25 °C
Reaction time: 8 h
Yield: 19.4 %

Procedure:
To a stirred solution of 2-(2-chlorobenzyloxy)-4-carboxy-6-methylquinoline (Method 7; 0.350 g, 1.067 mmol) and ethyl 2-aminothiazole-5-carboxylate (0.184 g, 1.067 mmol) in dimethyl formamide (DMF, 6 ml) was added 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (0.307 g, 1.601 mmol) and 4-dimethylaminopyridine (0.391 g, 3.202 mmol). The reaction mixture was stirred overnight at room temperature, and then diluted with ethyl acetate (20 ml). The mixture was washed with water (20 ml), and the aqueous washings extracted with ethyl acetate (3×15 ml); the organic phases were combined and concentrated in vacuo. Flash chromatography on silica gel, eluting with a gradient of 2–20% ethyl acetate in iso-hexane, gave the title compound as a colourless solid (0.100 g, 19%). NMR: 1.30 (3H, t), 2.40 (3H, s), 4.30 (2H, q), 6.65 (2H, d), 7.20 (2H, m), 7.55 (2H, m), 7.65 (1H, m), 7.75 (1H, d), 7.95 (1H, s), 8.10 (2H, m), 8.15 (1H, s); m/z 482 (M+H)+, 480 (M−H)+,
Reaction SMILES: [C:1]1([C:7]2([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:11]([CH2:12][NH:13][CH:14]([CH3:16])[CH3:15])[CH2:10][O:9][C:8]2=[O:17])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+]>C(CC(C)(C)C)(C)C>[C:18]1([C:7]2([C:1]3[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=3)[CH:11]([CH2:10][OH:9])[CH2:12][N:13]([CH:14]([CH3:15])[CH3:16])[C:8]2=[O:17])[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CC(C)NCC1COC(=O)C1(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(C)CC(C)(C)C
Product: CC(C)N1CC(CO)C(c2ccccc2)(c2ccccc2)C1=O
Reaction time: 8 h

Procedure:
Fifty-three grams (0.17 mole) of 4,5-dihydro-3,3-diphenyl-4-isopropylaminomethylfuran-2-(3H)one was dissolved in 300 ml. of boiling isooctane and 0.25 g. of 67% sodium hydride added. After refluxing for 6.5 hours an additional 0.25 g. of 57% sodium hydride was added and refluxing was continued overnight. The cooled mixture was filtered and the solid was recrystallized from toluene. The 3,3-diphenyl-4-hydroxymethyl-1-isopropyl-2-pyrrolidinone weighed 42 g. (80%) and melted at 159°-161° C. Analysis: Calcd. for C20H23NO2 : C, 77.64; H, 7.49; N, 4.53. Found: C, 77.71; H, 7.52; N, 4.37.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][C:3]=1[S:9](Cl)(=[O:11])=[O:10].[NH2:13][C:14]1[C:19]([OH:20])=[CH:18][CH:17]=[CH:16][C:15]=1[CH3:21].C(N(CC)CC)C>C(Cl)Cl>[NH2:13][C:14]1[C:15]([CH3:21])=[CH:16][CH:17]=[CH:18][C:19]=1[O:20][S:9]([C:3]1[CH:4]=[CH:5][C:6]([Cl:8])=[CH:7][C:2]=1[Cl:1])(=[O:11])=[O:10]
Reactant: Cc1cccc(O)c1N
Reactant: O=S(=O)(Cl)c1ccc(Cl)cc1Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: Cc1cccc(OS(=O)(=O)c2ccc(Cl)cc2Cl)c1N
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 2,4-dichlorobenzenesulfonyl chloride (20.2 g, 82.3 mmol) and 2-amino-m-cresol (11 g, 89.4 mmol) in 200 mL of methylene chloride, triethylamine (8.5 g, 83.4 mmol) was added dropwise at 5° C. The mixture was stirred at ambient temperature for 16 hours.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[CH:18]=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[C:14]([O:19][CH3:20])[CH:15]=3)[N:10]=2)=[CH:4][CH:3]=1.[Cl:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]=[C:29]=[S:30])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32]>>[CH3:20][O:19][C:14]1[CH:15]=[C:16]2[C:11](=[CH:12][CH:13]=1)[N:10]=[C:9]([S:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:29]([NH:28][C:25]3[CH:26]=[CH:27][C:22]([Cl:21])=[C:23]([C:31]([F:34])([F:32])[F:33])[CH:24]=3)=[S:30])=[CH:7][CH:6]=1)[CH:18]=[CH:17]2
Reactant: FC(F)(F)c1cc(N=C=S)ccc1Cl
Reactant: COc1ccc2nc(Sc3ccc(N)cc3)ccc2c1
Product: COc1ccc2nc(Sc3ccc(NC(=S)Nc4ccc(Cl)c(C(F)(F)F)c4)cc3)ccc2c1
Yield: 71.8 %

Procedure:
2-(4-aminophenylthio)-6-methoxyquinoline (15.0 moles, 4.2 g) and 4-chloro-3-trifluoromethylphenylisothiocyanate (15.0 mmoles, 3.6 g) were reacted according to procedure C to yield 5.6 g, 72% of the title compound. Mass Spec (FD) 519. Calculated for C24H17ClF3N3OS2 : C, 55.44; H, 3.30; N, 8.08. Found: C, 55.62; H, 3.43; N, 8.27.
Reaction SMILES: [F-:1].[F-].[F-].C(N(SN(CC)CC)CC)C.[C:15]([CH:17]([C:19]1[S:20][CH:21]=[C:22]([CH2:24][O:25]C2CCCCO2)[N:23]=1)O)#[CH:16].C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][CH:17]([C:19]1[S:20][CH:21]=[C:22]([CH2:24][OH:25])[N:23]=1)[C:15]#[CH:16]
Reactant: [F-]
Reactant: C#CC(O)c1nc(COC2CCCCO2)cs1
Agent: CCN(CC)SN(CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: C#CC(F)c1nc(CO)cs1
Temperature: -55 °C
Reaction time: 2 h

Procedure:
0.53 ml of diethylaminosulfide trifluoride (DAST) were added at about -60° C. to a solution of 1 g of the product of Stage C and 5 ml of methylene chloride and the reaction mixture was stirred for 2 hours at -55° C. and poured into a solution of sodium bicarbonate. Extraction was carried out with methylene chloride and the extracts were dried over magnesium sulfate, filtered and evaporated to dryness. The residue was taken up in 5 ml of methanol and 20 mg of toluene-sulfonic acid were added. The reaction mixture was stirred for one hour at 20° C., followed by evaporation to dryness. The residue was chromatographed on silica eluting with a hexane-ethyl acetate mixture (7-3) to obtain 0.16 g of the desired product with a Rf=0.10.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][C:3]([C:6]([OH:8])=O)=[CH:2]1.ON1C(=O)CCC1=O.Cl.C(N=C=NCCCN(C)C)C.[NH2:29][CH2:30][CH2:31][CH2:32][S:33][C:34]1[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=1>C(Cl)Cl>[S:1]1[CH:5]=[CH:4][C:3]([C:6]([NH:29][CH2:30][CH2:31][CH2:32][S:33][C:34]2[CH:39]=[CH:38][N:37]=[CH:36][CH:35]=2)=[O:8])=[CH:2]1
Reactant: NCCCSc1ccncc1
Reactant: O=C(O)c1ccsc1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: O=C1CCC(=O)N1O
Solvent: ClCCl
Product: O=C(NCCCSc1ccncc1)c1ccsc1
Yield: 76 %

Procedure:
To a solution of 1.00 g (7.80 mmol) of thiophene-3-carboxylic acid and 1.08 g 410.1 mmol) of N-hydroxysuccinimide in 70 ml of methylene chloride, 1.80 g (9.36 mmol) of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride was added under ice-cooling with stirring. The mixture was stirred at room temperature for 1 hour. Further, 1.31 g (7.80 mmol) of 4-(3-aminopropylthio)pyridine was added, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was washed with water and dried, and then the solvent was distilled off. The residue was purified by column chromatography (eluent: methanol/ethyl acetate=1:10) to obtain 1.65 g of the desired compound (yield: 76.1%, colorless powder).
Reaction SMILES: [CH3:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[H-].[Na+].I[CH3:14]>C1COCC1>[CH3:14][N:6]1[C:7]2[C:3](=[C:2]([CH3:1])[CH:10]=[CH:9][CH:8]=2)[CH:4]=[CH:5]1
Reactant: Cc1cccc2[nH]ccc12
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: Cc1cccc2c1ccn2C
Temperature: 0 °C
Reaction time: 0.27 h

Procedure:
To a solution of 4-methyl-1H-indole (CAS#16096-32-5, 2.82 mL, 22.9 mmol) in THF (100 mL) at 0° C. was added sodium hydride (60% dispersion in oil, 1.37 g, 34.3 mmol). The reaction was permitted to stir for 16 minutes at 0° C. and was then warmed to room temperature for 60 minutes. The reaction mixture was then re-cooled to 0° C. and iodomethane (1.86 mL, 29.7 mmol) was added. The reaction was then put at room temperature and permitted to stir for 45 minutes. The reaction was then quenched with saturated aqueous ammonium chloride and concentrated to approximately half of its original volume. The mixture was then diluted with water and dichloromethane and the layers were separated. The aqueous layer was then extracted two additional times with dichloromethane. The organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane 0 to 30%) to afford 1,4-dimethyl-1H-indole; 1H NMR (400 MHz, CDCl3) δ ppm 2.57 (s, 3H), 3.80 (s 3H), 6.51 (d, J=3.0 Hz, 1H), 6.93 (d, J=6.7 Hz, 1H), 7.06 (d, J=3.0 Hz, 1H), 7.13-7.21 (m, 2H).
Reaction SMILES: [N:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)=O.[C:9](=[S:11])=[S:10]>>[SH:11][C:9]1[S:10][C:4]2[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=2[N:1]=1
Reactant: S=C=S
Reactant: O=Nc1ccccc1
Product: Sc1nc2ccccc2s1

Procedure:
It must be considered surprising, that nitrosobenzene can be transformed substantially quantitatively to 2-mercaptobenzothiazole with hydrogen sulfide and carbon disulfide. The reaction may be represented by a summation formula, as follows: ##STR1## However, the reaction is in fact much more complicated and is composed of a great number of individual reactions partly taking place concurrently and partly taking place sequentially. At any rate, it can be stated with certainty that an initial quantitative reduction of the nitrosobenzene by hydrogen sulfide to aniline, which then reacts with carbon disulfide to 2-mercaptobenzothiazole in the known manner, is not possible. The main reaction product of nitrosobenzene and hydrogen sulfide is indeed aniline, which is formed with a yield of about 75%, but at least ten more reaction products with aromatic nitrogen groupings are also formed thereby. When this mixture of products is subsequently reacted with carbon disulfide, one nevertheless obtains an almost quantitative--based on the charged nitrosobenzene--yield of 2-mercaptobenzothiazole, thus a much higher yield than would correspond to the aniline content of the reaction mixture. It follows therefore, that, surprisingly, the other reaction products are also transformed into 2-mercaptobenzothiazole. Therefore, when the nitrosobenzene is being reacted with hydrogen sulfide and carbon disulfide at the same time, in keeping with the invention, the reaction will produce the desired 2-mercaptobenzothiazole with high selectivity and yield.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][NH2:10].N1C=CC=CC=1.[Cl:17][CH2:18][CH2:19][O:20][C:21](Cl)=[O:22]>O>[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][NH:10][C:21]([O:20][CH2:19][CH2:18][Cl:17])=[O:22]
Reactant: Cc1cccc(C)c1NN
Reactant: O=C(Cl)OCCCl
Solvent: O
Solvent: c1ccncc1
Product: Cc1cccc(C)c1NNC(=O)OCCCl
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a mixture of 127 g (0.935 mol) 2,6-dimethylphenylhydrazine, 102.5 g (1.3 mol) pyridine and 400 ml water is added, at 0°-5°, 133.5 g (0.935 mol) chloroformic acid β-chloroethyl ester. After the addition is complete, the mixture is stirred for 2 hours at room temperature, the formed precipitate filtered off, washed with water and dried. The so obtained title compound is recrystallised from toluene to yield colourless crystals, m.p. 74°-75°.
Reaction SMILES: [Li+].CC([N-]C(C)C)C.C([Li])CCC.C(NC(C)C)(C)C.C(N(CC)[C:24]([C:26]1[C:27]([C:36]2[CH:41]=[CH:40][C:39]([O:42][CH2:43][CH2:44][CH3:45])=[CH:38][C:37]=2[O:46][CH3:47])=[C:28]([O:32][CH:33]([CH3:35])[CH3:34])[CH:29]=[CH:30][CH:31]=1)=[O:25])C>C1COCC1>[CH:33]([O:32][C:28]1[CH:29]=[CH:30][CH:31]=[C:26]2[C:27]=1[C:36]1[C:37]([O:46][CH3:47])=[CH:38][C:39]([O:42][CH2:43][CH2:44][CH3:45])=[CH:40][C:41]=1[C:24]2=[O:25])([CH3:35])[CH3:34]
Reactant: CCCOc1ccc(-c2c(OC(C)C)cccc2C(=O)N(CC)CC)c(OC)c1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: CCCOc1cc(OC)c2c(c1)C(=O)c1cccc(OC(C)C)c1-2
Temperature: 25 °C
Reaction time: 1 h
Yield: 72.4 %

Procedure:
Prepare LDA reagent by reacting n-butyl lithium and diisopropylamine as in Example 7C to obtain 0.05 mole in THF (50 mL) at 0° C. At 0° C., dropwise add N,N-diethyl-6-isopropyloxy-2'-methoxy-4'-propyloxy-biphenyl-2-carboxamide (4.3 g, 0.011 mole) in THF (20 mL). Warm the mixture to ambient temperature, stir for 1 hour then heat to reflux for 1.5 hours. Workup the mixture as in Example 7C and chromatograph eluting with 50%/50% EtOAc/hexane to give the title compound as a red solid (2.6 g, 63%). m.p. 114°-116° C.
Reaction SMILES: [CH2:1]([O:4][C:5]([N:7]1[CH2:11][C@H:10](OS(C)(=O)=O)[CH2:9][C@H:8]1[CH2:17][OH:18])=[O:6])[CH:2]=[CH2:3].[C:19]([O-:22])(=[S:21])[CH3:20].[K+].C(OCC)(=O)C>CN(C)C=O>[C:19]([S:21][C@@H:10]1[CH2:11][N:7]([C:5]([O:4][CH2:1][CH:2]=[CH2:3])=[O:6])[C@H:8]([CH2:17][OH:18])[CH2:9]1)(=[O:22])[CH3:20]
Reactant: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1CO
Reactant: CC([O-])=S
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: C=CCOC(=O)N1C[C@@H](SC(C)=O)C[C@H]1CO
Temperature: 65 °C
Reaction time: 5 h
Yield: 85.5 %

Procedure:
A solution of (2S,4R)-1-allyloxycarbonyl-4-methanesulfonyloxypyrrolidine-2-methanol (19.32 g: 69.17 mmole) and 90% potassium thioacetate (10.73 g: 89.9 mmole) in dimethylformamide (217 ml) is heated with stirring at 65° C. for 5 hours. To the reaction mixture ethyl acetate (200 ml) and ice water (200 ml) are added. The organic layer is taken, successively washed with aqueous 0.05N-sodium hydroxide, 0.1N-hydrochloric acid, water and saturated brine, dried over magnesium sulfate, and concentrated in vacuo. The residue is purified by silica gel chromatography to give (2S,4S)-4-acetylthio-1-allyloxycarbonylpyrrolidine-2-methanol (15.34 g). Yield: 90%. NMR δ(CDCl3) ppm: 1.5 to 1.7(m, 1H), 2.34(s, 3H), 2.4 to 2.6(m, 1H), 3.19(dd, J=8.0 Hz, J=11.5 Hz, 1H), 3.6 to 3.8(m, 2H), 3.8 to 4.0(m, 1H), 4.0 to 4.2(m, 2H), 4.6(m, 2H), 5.2 to 5.4(m, 2H), 5.8 to 6.1(m, 1H).
Reaction SMILES: [CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]#[N:13])=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].[C:14](=O)([O:18]CC)[O:15][CH2:16][CH3:17].[O-]CC.[Na+].[Na]>C(O)C>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([CH:11]([C:12]#[N:13])[C:14]([O:15][CH2:16][CH3:17])=[O:18])=[CH:9][CH:10]=1)[CH:2]([CH3:4])[CH3:3]
Reactant: CCOC(=O)OCC
Reactant: CC(C)Cc1ccc(CC#N)cc1
Agent: CC[O-]
Agent: [Na+]
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(C#N)c1ccc(CC(C)C)cc1
Reaction time: 1 h

Procedure:
A mixture of 52 grams (0.31 mol) of 4-isobutylphenylacetonitrile (Preparation 1) and 230 grams (1.95 mols) of diethyl carbonate was heated in a flask provided with a thermometer, stirrer, dropping funnel, and distillation column having a length of 19 centimeters filled with Fenske rings. When the temperature of the mixture had reached 90° C, a solution of sodium ethoxide in ethanol that was freshly prepared from 9.2 grams (0.4 mol) of sodium metal and 200 milliliters of ethanol was added drop by drop from the dropping funnel while the vapors formed were permitted to distill through the distillation column. After the temperature reached between 120° and 130° C, no further vapors were distilled and the mixture was stirred vigorously for an additional period of 1 hour. Thereafter, the mixture remaining in the flask was cooled and the flask was surrounded with cracked ice and a solution of 35 milliliters of glacial acetic acid in 130 milliliters of water was added thereto with stirring. The organic phase was then separated from the aqueous phase. The aqueous phase was extracted with ether and the extract was combined with the organic phase, which was then successively washed with a saturated aqueous solution of sodium bicarbonate and water and dried over anhydrous magnesium sulfate. The dried liquid was then filtered to separate the solids therefrom and the filtrate was distilled under vacuum, the fraction distilling between 150° and 155° C at a pressure of 1 millimeter of mercury, which is the ethyl 2-(4-isobutylphenyl)cyanoacetate, was collected.