Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[O:3]=[C:4]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:13]([NH2:15])=[O:14])[CH:10]=2)[NH:5]1.[Cl:16][C:17]1[N+:22]([O-])=[CH:21][C:20]([CH2:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[CH:19][CH:18]=1.P(Cl)(Cl)Cl>CN(C)C=O.C([O-])(O)=O.[Na+].C(OCC)(=O)C>[ClH:16].[OH:3][C:4]1[NH:5][C:6]2[C:11]([C:12]=1[C:17]1[CH:18]=[CH:19][C:20]([CH2:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[CH:21][N:22]=1)=[CH:10][C:9]([C:13]([NH2:15])=[O:14])=[CH:8][CH:7]=2
Reactant: [O-][n+]1cc(CN2CCOCC2)ccc1Cl
Reactant: NC(=O)c1ccc2c(c1)CC(=O)N2
Agent: O=C([O-])O
Agent: [H-]
Agent: [Na+]
Solvent: ClP(Cl)Cl
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: Cl
Product: NC(=O)c1ccc2[nH]c(O)c(-c3ccc(CN4CCOCC4)cn3)c2c1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Sodium hydride (0.090 g of 60% suspension in mineral oil, 2.25 mmol) was added to a cooled (0° C.) solution of 2-oxoindoline-5-carboxamide (0.315 g, 1.79 mmol) in N,N-dimethylformamide (5 mL). The reaction mixture was stirred at 0° C. for 15 min under an N2 atmosphere, followed by the addition of 4-[(6-chloro-1-oxidopyridin-3-yl)methyl]morpholine (0.345 g, 1.51 mmol) in N,N-dimethylformamide (2 mL). The reaction vessel was closed, immediately warmed up to 130° C., and the reaction was stirred at this temperature for 0.5 h. The cooled mixture was diluted with a saturated NaHCO3 solution (30 mL), and extracted with ethyl acetate (containing 5% methanol). The combined organic extracts were dried (Na2SO4), and the solvents were removed in vacuo. The residue was dissolved in toluene (100 mL), and re-evaporated. The material was dried, dissolved in ethyl acetate (75 mL), and phosphorus trichloride (0.6 mL, 6 mmol) in ethyl acetate (5 mL) was added dropwise under vigorous stirring. The reaction mixture was heated to reflux for 2 h, cooled to room temperature, and quenched with an excess of saturated sodium hydrogen carbonate. The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (containing 5% methanol). The combined organic extracts were dried (Na2SO4), the solvents were removed in vacuo, and the residue was purified on a silica gel column using chloroform/methanol/aqueous NH3, (100:10:1), as the eluent to afford the title compound as the base, yield 0.013 g (2.5%). This material was dissolved in chloroform/methanol (1:1), and treated with HCl in diethyl ether (1 M) followed by addition of diethyl ether. The resulting yellow crystals were collected by filtration and washed with diethyl ether to afford 0.010 g of the title compound: 1H NMR (DMSO-d6, 300 MHz) δ 14.70 (br s, 1H), 11.08 (br s, 1H), 10.68 (s, 1H), 8.21 (s, 1H), 8.05-7.95 (m, 2H), 7.84 (d, J=9.0 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 7.10 (br s, 1H), 6.92 (d, J=8.0 Hz, 1H), 4.26 (s, 2H), 3.97-3.92 (m, 2H), 3.80-3.72 (m, 2H), 3.40-3.33 (m, 2H), 3.13-3.07 (m, 2H); MS (ES) m/z 354 (M++1).
Reaction SMILES: [CH3:1][C:2]([CH3:7])([CH3:6])[C:3]([NH2:5])=[S:4].Cl[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11].[CH2:15](O)[CH3:16]>>[CH2:13]([O:12][C:10]([C:9]1[S:4][C:3]([C:2]([CH3:7])([CH3:6])[CH3:1])=[N:5][C:15]=1[CH3:16])=[O:11])[CH3:14]
Reactant: CCO
Reactant: CCOC(=O)CCl
Reactant: CC(C)(C)C(N)=S
Product: CCOC(=O)c1sc(C(C)(C)C)nc1C

Procedure:
A solution of 2,2-dimethyl-thiopropionamide (7.7 g, 65.8 mmol) and ethyl 2-chloroacetate (9.26 mL, 67 mmol) in 150 mL of ethanol was heated at reflux temperature for 24 h. The reaction mixture was concentrated under reduced pressure, suspended in ethyl acetate, and washed with saturated aqueous sodium bicarbonate and brine solutions. The organic fraction was dried over anhydrous magnesium sulfate and concentrated to 14.1 g of an orange viscous material. MS (ESI+): 229.4 (M+1).
Reaction SMILES: [CH3:1][Mg]Br.[Br:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12](=[O:14])[CH3:13])[CH:8]=[CH:9][CH:10]=1>C(OCC)C>[Br:4][C:5]1[CH:6]=[C:7]([CH2:11][C:12]([CH3:1])([OH:14])[CH3:13])[CH:8]=[CH:9][CH:10]=1
Reactant: CC(=O)Cc1cccc(Br)c1
Reactant: C[Mg]Br
Solvent: CCOCC
Product: CC(C)(O)Cc1cccc(Br)c1
Temperature: 0 °C
Reaction time: 3 h
Yield: 82.7 %

Procedure:
Methylmagnesium bromide (3M solution in diethylether, 51.6 ml, 155 mmol) was slowly added to a solution of 1-(3-bromo-phenyl)propan-2-one (15.0 g, 70 mmol) in dry diethylether (200 ml) at 0° C. The resulting mixture was left for 3 hours, then cooled to 0° C. and slowly quenched with saturated aqueous ammonium chloride solution. The organic phase was washed with brine, dried (sodium sulfate). The yellow oil was then purified by column chromatography on silica gel eluting with dichloromethane:pentane:methanol (90:5:5 by volume to afford a pale yellow oil (13.26 g).
Reaction SMILES: [CH:1]1([Li])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[CH2:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1.C([Li])CCC.[CH3:25][Si:26]([CH3:29])(Cl)Cl>>[CH3:25][Si:26]([CH3:29])([CH:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12]1)[CH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: C[Si](C)(Cl)Cl
Reactant: C1=Cc2ccccc2C1
Reactant: [Li]C1C=Cc2ccccc21
Agent: [Li]CCCC
Product: C[Si](C)(C1C=Cc2ccccc21)C1C=Cc2ccccc21
Yield: 71 %

Procedure:
In detail, in Japanese Patent Laid-Open Publication No. 221285/1990 for example, a solution of an indenyl lithium salt prepared from indene and n-butyllithium is slowly added to a dimethyldichlorosilane solution, and they are reacted with each other overnight to obtain dimethyldi(1-indenyl)silane in a 71% yield. In Japanese Patent Laid-Open Publication No. 268307/1992, dimethyldi (2-methyl-1-indenyl) silane is obtained in a 16% yield in a manner similar to the above.
Reaction SMILES: [CH:1](=O)[CH:2]([CH3:4])[CH3:3].[Na].[PH2:7]([O-:9])=[O:8].[CH:10]([NH3+:23])([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>>[CH:10]([NH:23][CH:1]([P:7]([OH:9])[OH:8])[CH:2]([CH3:4])[CH3:3])([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: [NH3+]C(c1ccccc1)c1ccccc1
Reactant: O=[PH2][O-]
Reactant: CC(C)C=O
Agent: [Na]
Product: CC(C)C(NC(c1ccccc1)c1ccccc1)P(O)O

Procedure:
7.2 parts of isobutyraldehyde in 15 parts of sodium-dried dioxan was added to a suspension of 25 parts of benzhydrylammonium hypophosphite in 150 parts of sodium-dried dioxan under reflux. 80 Parts of dioxan was removed and 150 parts of alcohol added. After cooling the mixture was filtered to give DL-1-benzhydrylamino-2-methylpropanephosphonous acid, melting point 189°-192° identical to that obtained in Example 2A.
Reaction SMILES: [CH2:1]([O:6][C:7]1[CH:8]=[C:9]([CH:13]=[C:14]([O:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[CH:15]=1)[C:10]([OH:12])=O)[CH:2]=[C:3]([CH3:5])[CH3:4].[NH2:22][CH2:23][CH:24]1[CH2:28][CH2:27][CH2:26][N:25]1[CH2:29][CH3:30]>>[CH2:29]([N:25]1[CH2:26][CH2:27][CH2:28][CH:24]1[CH2:23][NH:22][C:10](=[O:12])[C:9]1[CH:13]=[C:14]([O:16][CH2:17][CH:18]=[C:19]([CH3:21])[CH3:20])[CH:15]=[C:7]([O:6][CH2:1][CH:2]=[C:3]([CH3:4])[CH3:5])[CH:8]=1)[CH3:30]
Reactant: CC(C)=CCOc1cc(OCC=C(C)C)cc(C(=O)O)c1
Reactant: CCN1CCCC1CN
Product: CCN1CCCC1CNC(=O)c1cc(OCC=C(C)C)cc(OCC=C(C)C)c1
Yield: 39 %

Procedure:
In a manner identical to Example 15, 3,5-diprenyloxybenzoic acid(1.45 g) was subjected to a condensation reaction with 2-aminomethyl-1-ethylpyrrolidine (0.7 ml), thereby yielding 0.78 g(39%) of the aimed compound.
Reaction SMILES: [N+:1]([C:4]1[CH:25]=[CH:24][C:7]([O:8][C:9]2[CH:23]=[CH:22][CH:21]=[CH:20][C:10]=2[C:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[CH:6][CH:5]=1)([O-])=O.[H][H]>C(O)C.[Pd]>[NH2:1][C:4]1[CH:25]=[CH:24][C:7]([O:8][C:9]2[CH:23]=[CH:22][CH:21]=[CH:20][C:10]=2[C:11]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:12])=[CH:6][CH:5]=1
Reactant: [H][H]
Reactant: O=C(Oc1ccccc1)c1ccccc1Oc1ccc([N+](=O)[O-])cc1
Agent: [Pd]
Solvent: CCO
Product: Nc1ccc(Oc2ccccc2C(=O)Oc2ccccc2)cc1
Yield: 91.8 %

Procedure:
9 g of phenyl 2-(4'-nitrophenoxy)benzoate, prepared as described in Example 1, are contacted with hydrogen in 50 cm3 of ethanol, in the presence of 5% palladium (100 mg) on coal. After recrystallization in 100 cm3 of a methanol-water mixture (50--50 by volume), 7.52 g of phenyl 2-(4'-aminophenoxy)benzoate (m.p. 102° C.) are obtained (yield: 92%).
Reaction SMILES: [CH2:1]([O:3][CH:4]([O:10][CH2:11][CH3:12])[C:5](OCC)=[O:6])[CH3:2].[OH-].[NH4+:14]>C(Cl)Cl>[CH2:1]([O:3][CH:4]([O:10][CH2:11][CH3:12])[C:5]([NH2:14])=[O:6])[CH3:2]
Reactant: [NH4+]
Reactant: CCOC(=O)C(OCC)OCC
Agent: [OH-]
Solvent: ClCCl
Product: CCOC(OCC)C(N)=O
Reaction time: 3 h
Yield: 87 %

Procedure:
A mixture of 24.85 g of ethyl diethoxyacetate and 140 ml of concentrated ammonium hydroxide was stirred for 3 hours. The ammonia and H2O were evaporated under reduced pressure on a water bath at 50°-60° leaving a wet solid. The wet solid was dried in a vacuum oven at 53° for 18 hours giving a dark pink solid. The solid was dissolved in CH2Cl2. The solution was filtered to remove a small amount of red insoluble material. The filtrate was concentrated and Skellysolve B was added. Cooling gave 18.0 g (87%) of diethoxyacetamide as orange plates, m.p. 76.5-79°.
Reaction SMILES: C[Si](C)(C)[O:3][C:4]([C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)=[CH2:5].[F-].[Cs+].[CH:15]1([CH:21]=[CH:22][C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1>CS(C)=O>[CH:15]1([CH:21]([CH2:3][C:4]([C:6]2[O:7][CH:8]=[CH:9][CH:10]=2)=[O:5])[CH2:22][C:23]([C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([OH:31])[CH:26]=2)=[O:24])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: O=C(C=CC1CCCCC1)c1cccc(O)c1
Reactant: C=C(O[Si](C)(C)C)c1ccco1
Agent: [Cs+]
Agent: [F-]
Solvent: CS(C)=O
Product: O=C(CC(CC(=O)c1ccco1)C1CCCCC1)c1cccc(O)c1
Temperature: 70 °C

Procedure:
1-Trimethylsilyloxy-1-(furan-2-yl)ethylene (1.66 g, 9.1 mmol; prepared according to J. Chem. Soc., Perkin Trans. I 1989, 1585) and CsF (0.41 g, 2.7 mmol) were added to a suspension of 3-cyclohexyl-1-(3-hydroxyphenyl)-2-propen-1-one on Wang resin (2.6 g, 1.82 mmol) in dimethyl sulfoxide (30 mL). The reaction mixture was heated to 70° C. for 3 h and the reaction was quenched with 10% AcOH/CH2Cl2. The resin was filtered, washed with DMF (×2) and alternating MeQH and CH2Cl2 (×5), and dried under high vacuum overnight to give 2.7 g of 3-cyclohexyl-1-(3-hydroxyphenyl)-5-(furan-2-yl)-1,5-pentanedione on Wang resin.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH3:27])=[O:25])[CH2:20]2)=[CH:15][CH:14]=1.Cl([O-])=[O:29].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O.CC(=CC)C>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:29])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH:19]2[CH2:23][CH2:22][N:21]([C:24]([O:26][CH3:27])=[O:25])[CH2:20]2)=[CH:15][CH:14]=1
Reactant: COC(=O)N1CCC(c2ccc(-c3cc4c(C=O)c[nH]c4cc3Cl)cc2)C1
Reactant: [O-][Cl+][O-]
Agent: CC=C(C)C
Agent: O=P([O-])(O)O
Agent: [Na+]
Solvent: CC(C)(C)O
Solvent: O
Solvent: CC#N
Product: COC(=O)N1CCC(c2ccc(-c3cc4c(C(=O)O)c[nH]c4cc3Cl)cc2)C1
Temperature: 0 °C
Reaction time: 2 h
Yield: 46.3 %

Procedure:
To a solution of methyl 3-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenyl]pyrrolidine-1-carboxylate (124 mg, 0.325 mmol) in acetonitrile (4 mL) and tert-butanol (4 mL) was added 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (327 mg, 3.59 mmol) and sodium phosphate monobasic dihydrate (761 mg, 4.875 mmol) in water (2 mL). After the resulting mixture was stirred for 2 hours at room temperature, additional sodium chlorite (435.5 mg, 4.79 mmol) and sodium phosphate monobasic dihydrate (1.014 g, 6.5 mmol) in water (2 mL) and 2-methyl-2-butene (1 mL) was added. The resulting mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated in vacuo and the aqueous residue was extracted with EtOAc (3×20 mL). The combined organic layers were dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in DMSO and purified via prep-HPLC to give 6-chloro-5-{4-[1-(methoxycarbonyl)pyrrolidin-3-yl]phenyl}-1H-indole-3-carboxylic acid (60 mg, 46%) as a white solid. The racemic mixture was separated by preparative chiral SFC to give 16 mg of peak 1 or Example 14A (>99% ee, ret time=4.73 minutes), and 17 mg of peak 2 or Example 14B (>93% ee, ret time=5.33 minutes) using ChiralPak AD-H Minigram-1, 60/40 CO2/MeOH 0.2% isopropylamine, 10 mL/min, 120 Bar. MS (ES+) 398.9 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ 12.14 (br, 1H), 11.97 (s, 1H), 8.08 (d, 1H), 7.94 (s, 1H), 7.61 (s, 1H), 7.38 (m, 4H), 3.81 (m, 1H), 3.61 (s, 3H), 3.54 (m, 1H), 3.40 (m, 2H), 3.28 (m, 1H), 2.25 (m, 1H), 2.00 (m, 1H).
Reaction SMILES: [CH2:1]([N:13]1[CH:17]([OH:18])[CH:16]([OH:19])[N:15]([CH2:20][O:21]C)[C:14]1=[O:23])[N:2]1[CH:6]([OH:7])[CH:5]([OH:8])[N:4]([CH2:9][O:10]C)[C:3]1=[O:12].C(N1C(O)C(O)N(CCO)C1=O)N1C(O)C(O)N(CCO)C1=O.OC1C(O)N(COC)C(=O)N1COC>>[CH2:1]([N:2]1[CH:6]([OH:7])[CH:5]([OH:8])[N:4]([CH2:9][OH:10])[C:3]1=[O:12])[N:13]1[CH:17]([OH:18])[CH:16]([OH:19])[N:15]([CH2:20][OH:21])[C:14]1=[O:23]
Reactant: COCN1C(=O)N(CN2C(=O)N(COC)C(O)C2O)C(O)C1O
Agent: COCN1C(=O)N(COC)C(O)C1O
Agent: O=C1N(CCO)C(O)C(O)N1CN1C(=O)N(CCO)C(O)C1O
Product: O=C1N(CO)C(O)C(O)N1CN1C(=O)N(CO)C(O)C1O

Procedure:
1,1'-methylenebis(3-methoxymethyl-4,5-dihydroxyimidazolidin-2-one) (Example 4); 1,1'-methylenebis[3-(2-hydroxyethyl)-4,5-dihydroxyimidazolidin-2-one] (Example 5); and 4,5-dihydroxy-1,3-di(methoxymethyl)-2-imidazolidinone (Example 6) are evaluated as adhesion promoters in natural rubber, as follows:
Reaction SMILES: [Na].[NH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH2:9]=O.[N:11]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH:15]=[CH:14][CH2:13][CH2:12]1>CO>[N:11]1([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:12]2[C@@H:13]([CH2:9][NH:2][CH:3]3[CH:8]2[CH:7]=[CH:6][CH:5]=[CH:4]3)[CH2:14][CH2:15]1
Reactant: C=O
Reactant: CC(C)(C)OC(=O)N1C=CCC1
Reactant: Nc1ccccc1
Agent: [Na]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC[C@@H]2CNC3C=CC=CC3[C@@H]21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 13 %

Procedure:
Sodium (1.2 g, 50 mmol) was dissolved in methanol (15 ml), aniline (0.9 g, 10 mmol) was added at room temperature, and the mixture was stirred for 10 min. This mixture was added to a suspension of paraformaldehyde (0.42 g, 14 mmol) in methanol (10 ml), and the mixture was stirred at room temperature for 5 hrs. The reaction mixture was poured into ice water, and the mixture was extracted with diethyl ether. The extract was dried (over anhydrous MgSO4), and the solvent was evaporated under reduced pressure. The residue was dissolved in methanol (20 ml), tert-butyl 2,3-dihydro-1H-pyrrole-1-carboxylate (850 mg, 5 mmol) was added and the mixture was heated under reflux for 18 hrs. The residue was subjected to column chromatography using silica gel (30 g) and eluted with hexane-ethyl acetate (9:1-4:1, v/v) to give the title compound (180 mg, 12%) as an amorphous form.
Reaction SMILES: F[C:2]1[C:6]([F:8])([F:7])[C:5]([F:10])([F:9])[C:4]([F:12])([F:11])[C:3]=1F.[CH3:14][C:15]1[CH:21]=[CH:20][C:18]([O-:19])=[CH:17][CH:16]=1.[Na+].[N+:23]([C:26]1[CH:31]=[CH:30][C:29]([OH:32])=[CH:28][CH:27]=1)([O-:25])=[O:24].C(N(CC)CC)C>CN(C)C=O.O>[CH3:14][C:15]1[CH:21]=[CH:20][C:18]([O:19][C:2]2[C:6]([F:8])([F:7])[C:5]([F:10])([F:9])[C:4]([F:12])([F:11])[C:3]=2[O:32][C:29]2[CH:30]=[CH:31][C:26]([N+:23]([O-:25])=[O:24])=[CH:27][CH:28]=2)=[CH:17][CH:16]=1
Reactant: FC1=C(F)C(F)(F)C(F)(F)C1(F)F
Reactant: O=[N+]([O-])c1ccc(O)cc1
Reactant: Cc1ccc([O-])cc1
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Solvent: O
Product: Cc1ccc(OC2=C(Oc3ccc([N+](=O)[O-])cc3)C(F)(F)C(F)(F)C2(F)F)cc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
21.2 g (0.1 mol) of perfluorocyclopentene were added dropwise at 5° C. to 13 g (0.1 mol) of sodium 4-methylphenoxide in 50 ml of dimethylformamide in the course of 15 minutes. After stirring at room temperature for 8 hours, a solution of 13.9 (0.1 mol) of 4-nitrophenol and 10.1 g of triethylamine in 50 ml of dimethylformamide was added dropwise to the reaction mixture, which was stirred for a further 6 hours at 40° C. The reaction mixture was then stirred into 300 ml of water and the organic phase was separated off after addition of 100 ml of methylene chloride. The organic phase was then washed successively with 50 ml of water, 50 ml of 5% strength hydrochloric acid and again with 50 ml of water, dried over sodium sulphate and evaporated to dryness on a rotary evaporator. The crude yield of product was 34 g. It was recrystallized from petroleum ether and 20 g of crystalline material were thus obtained, which corresponds to 47.7% of theory. The crystalline material had a melting point of 72° to 76° C. and showed a value for m/e of 419 for the molecular ion in the mass spectrum.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH3:9])=[N:6][CH:7]=1.C(O[CH:13]=[C:14]([C:20]([O:22][CH2:23][CH3:24])=[O:21])[C:15]([O:17][CH2:18][CH3:19])=[O:16])C>>[CH2:8]([C:5]1[N:6]=[CH:7][C:2]([NH:1][CH:13]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:3][CH:4]=1)[CH3:9]
Reactant: CCc1ccc(N)cn1
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Product: CCOC(=O)C(=CNc1ccc(CC)nc1)C(=O)OCC

Procedure:
A mixture of 5-amino-2-ethylpyridine (17.6 g) and diethyl ethoxymethylenemalonate (23.25 g) was heated on a steam bath for 2.5 hours. The mixture was cooled in ice. The solid formed was ground up in petroleum ether, b.p. 60°-80° C. and then filtered to give diethyl 2-(6-ethyl-3-pyridylaminomethylene)malonate, m.p. 55°-57° C.
Reaction SMILES: [CH3:1][S:2]([CH:4]1[C:13](=[O:14])[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]=[CH:5]1)=[O:3].C(=O)([O-])[O-].[K+].[K+].[CH2:21](Br)[CH2:22][CH2:23][CH3:24]>CC(C)=O>[CH2:21]([N:6]1[C:7]2[C:12](=[CH:11][CH:10]=[CH:9][CH:8]=2)[C:13](=[O:14])[C:4]([S:2]([CH3:1])=[O:3])=[CH:5]1)[CH2:22][CH2:23][CH3:24]
Reactant: CS(=O)C1C=Nc2ccccc2C1=O
Reactant: CCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCCn1cc(S(C)=O)c(=O)c2ccccc21

Procedure:
A mixture of 3-methylsulphinyl-4-quinolone (1.035 g.), anhydrous potassium carbonate (1.38 g.), n-butyl bromide (0.685 g.) and dry acetone (50 ml.) was refluxed for 24 hours. The mixture was filtered and the filtrate evaporated to dryness. The resulting oil was dissolved in chloroform (50 ml.). The solution was washed with water, dried and evaporated. The residue oil was triturated with light petroleum to give the solid product 1-n-butyl-3-methylsulphinyl-4-quinolone, m.p. 103°-105°.
Reaction SMILES: CC1C=CC([C:8]([OH:10])=[O:9])=CC=1.[C:11](O)(=[O:21])[C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=[O:17])=[CH:14][CH:13]=1>[Ru]>[C:8](=[O:10])=[O:9].[C:16]([C:15]1[CH:19]=[CH:20][C:12]([CH:11]=[O:21])=[CH:13][CH:14]=1)([OH:18])=[O:17]
Reactant: O=C(O)c1ccc(C(=O)O)cc1
Reactant: Cc1ccc(C(=O)O)cc1
Agent: [Ru]
Product: O=C=O
Product: O=Cc1ccc(C(=O)O)cc1

Procedure:
The reaction was conducted in the same manner as in Example 16 except that a product formed by charging 0.42 g of ruthenium chloride, 4.78 g of the deficient silicotungstate (K8 [SiW11O39 ].13H2O) obtained in Example 1 and 150 ml of water into a reactor at the same time (ruthenium concentration 1,000 ppm, a molar ratio of ruthenium to heteropoly-acid salt=1:1) was used as a catalyst. Consequently, the conversion of p-toluic acid was 75%. The selectivity for terephthalic acid relative to p-toluic acid reacted was 72%. As the other products, carbon dioxide and 4-carboxybenzaldehyde were formed in the selectivities of 27% and 1% respectively.
Reaction SMILES: Cl.Cl.[NH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([NH:19][C@@H:20]1[C:26](=[O:27])[N:25]([CH2:28][C:29]([OH:31])=[O:30])[C:24]2[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=2[S:22][CH2:21]1)[C:14]([O:16]CC)=[O:15].C(O)(=O)C.O.CO>[OH-].[Na+]>[NH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C@H:13]([NH:19][C@@H:20]1[C:26](=[O:27])[N:25]([CH2:28][C:29]([OH:31])=[O:30])[C:24]2[CH:32]=[CH:33][CH:34]=[CH:35][C:23]=2[S:22][CH2:21]1)[C:14]([OH:16])=[O:15]
Reactant: CCOC(=O)[C@H](CCCCCCCCCN)N[C@H]1CSc2ccccc2N(CC(=O)O)C1=O
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: CC(=O)O
Product: NCCCCCCCCC[C@H](N[C@H]1CSc2ccccc2N(CC(=O)O)C1=O)C(=O)O
Yield: 52.4 %

Procedure:
A solution of 3(R)-[10-amino-1(S)-ethoxycarboxyldecyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid (0.28 g) obtained in Example 74 in 1N sodium hydroxide (7 ml) stands for 1 hour at room temperature. After addition of acetic acid (2 ml) and water (5 ml), the mixture is subjected to Amberlite XAD-2 column chromatography (methanol:water=1:1). The eluate is concentrated under reduced pressure. The deposited crystal is collected by filtration and dried to yield 3(R)-[10-amino-1(S)-carboxydecyl]amino-4-oxo-2,3,4,5-tetrahydro-1,5-benzothiazepine-5-acetic acid (0.12 g).
Reaction SMILES: [NH:1]([C:3](=[O:15])[CH2:4][CH2:5][N:6]([CH3:14])[C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[NH2:2].[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33](O)=[O:34])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:16]([O:23][N:24]1[C:30](=[O:31])[N:29]2[CH2:32][C@H:25]1[CH2:26][CH2:27][C@H:28]2[C:33]([NH:2][NH:1][C:3](=[O:15])[CH2:4][CH2:5][N:6]([CH3:14])[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])=[O:34])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1
Reactant: CN(CCC(=O)NN)C(=O)OC(C)(C)C
Reactant: O=C(O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CN(CCC(=O)NNC(=O)[C@@H]1CC[C@@H]2CN1C(=O)N2OCc1ccccc1)C(=O)OC(C)(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 79.2 %

Procedure:
To a 0° C. solution of tert-butyl 3-hydrazinyl-3-oxopropyl(methyl)carbamate (4.3 g, 19.8 mmol) and (2S,5R)-6-(benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid (4.9 g, 0.0178 mol) in DMF (100 mL) was added HATU (8.2 g, 0.0218 mol), followed by dropwise addition of DIPEA (9.6 mL, 0.0594 mol) slowly. The mixture was stirred at 0° C. for 1 h, and then quenched with ice water. The aqueous layer was extracted with EtOAc (2×). The combined organic layer was dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography (gradient elution 20˜60% EtOAc/petroleum ether) to afford tert-butyl 3-(2-((2S,5R)-6-(benzyloxy)-7-oxo-1,6-diaza-bicyclo[3.2.1]octane-2-carbonyl)hydrazinyl)-3-oxopropyl(methyl)carbamate (6.7 g, 78%) as a white solid. ESI-MS (EI+, m/z): 476 [M+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[C:4]([F:10])[CH:3]=1.C(O)(=O)[CH2:12][C:13]([OH:15])=[O:14]>CN(C)C1C=CN=CC=1.CN(C=O)C.O>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH:12][C:13]([OH:15])=[O:14])=[C:4]([F:10])[CH:3]=1
Reactant: O=C(O)CC(=O)O
Reactant: O=Cc1ccc(Br)cc1F
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: CN(C)C=O
Product: O=C(O)C=Cc1ccc(Br)cc1F
Yield: 85 %

Procedure:
A mixture of 4-bromo-2-fluorobenzaldehyde (12.4 g, 61 mmol), malonic acid (12.7 g, 122 mmol) and 4-dimethylamino pyridine (0.75 g, 6.1 mmol) in 20 mL of DMF was heated at 100 degrees Celsius for 2 hrs. After cooling, the reaction mixture was diluted with 300 mL water, and filtered. The solid was collected, and triturated in hexane. The solid was collected and dried in vacuum to give 12.7 g (85%) of a white solid. MS: calc'd 243 (M−H), exp 243 (M−H).