Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]=[S:2]1(=[O:17])[CH2:6][CH2:5][CH2:4][N:3]1[C:7]1[CH:15]=[CH:14][C:10]([C:11]([OH:13])=O)=[C:9]([F:16])[CH:8]=1.Cl.[CH:19]1([C:22]2[C:23]([N:29]3[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]3)=[N:24][CH:25]=[C:26]([CH3:28])[CH:27]=2)[CH2:21][CH2:20]1>>[CH:19]1([C:22]2[C:23]([N:29]3[CH2:34][CH2:33][N:32]([C:11]([C:10]4[CH:14]=[CH:15][C:7]([N:3]5[CH2:4][CH2:5][CH2:6][S:2]5(=[O:1])=[O:17])=[CH:8][C:9]=4[F:16])=[O:13])[CH2:31][CH2:30]3)=[N:24][CH:25]=[C:26]([CH3:28])[CH:27]=2)[CH2:20][CH2:21]1
Reactant: Cc1cnc(N2CCNCC2)c(C2CC2)c1
Reactant: O=C(O)c1ccc(N2CCCS2(=O)=O)cc1F
Agent: Cl
Product: Cc1cnc(N2CCN(C(=O)c3ccc(N4CCCS4(=O)=O)cc3F)CC2)c(C2CC2)c1
Yield: 48.7 %

Procedure:
Using 4-(1,1-dioxo-1λ6-isothiazolidin-2-yl)-2-fluorobenzoic acid (259 mg) described in Preparation Example 23 and 1-(3-cyclopropyl-5-methylpyridin-2-yl)piperazine hydrochloride (254 mg) described in Preparation Example 85 and by the reaction and treatment in the same manner as in Example 86, the title compound (223 mg) was obtained.
Reaction SMILES: C1(C(C)C)C=CC=CC=1.[CH2:10]([C:12]1[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=1)[CH3:11]>>[CH3:18][C:15]1[CH:16]=[CH:17][C:12]([CH:10]=[CH2:11])=[CH:13][CH:14]=1
Reactant: CCc1ccc(C)cc1
Solvent: CC(C)c1ccccc1
Product: C=Cc1ccc(C)cc1

Procedure:
This example illustrates the dehydrogenation of cumene and p-ethyltoluene using a diluent comprising steam and nitrogen. Three and three-tenths grams of the catalyst prepared in Example II, ground to 18 to 40 mesh, was employed in the reactor described in Example II. Initially p-ethyltoluene was flowed into the reactor at 0.38 liquid hour space velocity, 11:1 diluent to p-ethyltoluene ratio (8:1 steam and 3:1 nitrogen) at 588° C., yielding a relatively poor conversion and selectivity. The catalyst was decoked with 5% oxygen and nitrogen for about 1 hr. Cumene was then run at 0.38 liquid hour space velocity, 11:1 diluent ratio (8:1 steam and 3:1 nitrogen) at 588° C. providing 40% conversion to alphamethylstyrene and 88% selectivity. The feed was then switched from cumene to p-ethyltoluene using the same diluent dilution and conditions providing 22% conversion to p-methylstyrene and 93% selectivity. Conditions were then changed to 0.72 liquid hour space velocity, 10:1 diluent ratio for the p-ethyltoluene (8:1 steam and 2:1 nitrogen) at 598° C., yielding 40% conversion and 92% selectivity to p-methylstyrene.
Reaction SMILES: C([Li])CCC.[F:6][C:7]([F:15])([F:14])[CH:8]([OH:13])[C:9]([F:12])(F)[F:10].[CH:16]12[CH2:22][CH:19]([CH:20]=[CH:21]1)[CH2:18][CH:17]2[CH:23]=[O:24].Cl.[O:26]1CCCC1>>[CH:16]12[CH2:22][CH:19]([CH:20]=[CH:21]1)[CH2:18][CH:17]2[CH:23]([OH:24])[C:9]([F:12])([F:10])[C:8]([OH:26])([OH:13])[C:7]([F:15])([F:14])[F:6]
Reactant: C1CCOC1
Reactant: O=CC1CC2C=CC1C2
Reactant: OC(C(F)(F)F)C(F)(F)F
Agent: Cl
Agent: [Li]CCCC
Product: OC(C1CC2C=CC1C2)C(F)(F)C(O)(O)C(F)(F)F
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 79.8 %

Procedure:
1290 mL of butyllithium (1.6 M hexane solution) was added to a mixture of 168 g of 1,1,1,3,3,3-hexafluoro-2-propanol and 1200 g of tetrahydrofuran at −70° C. under a nitrogen atmosphere. The temperature was increased to 0° C. gradually, and stirred at the temperature for 30 minutes. Then, 134 g of 5-norbornene-2-carbaldehyde was added thereto at 0° C. After stirring for 1 hour, dilute hydrochloric acid was added to terminate the reaction and to neutralize it. After the standard aqueous work-up, the product was purified by silica gel column chromatography to yield 230 g of 1-(5-norbornene-2-yl)-2,2,4,4,4-pentafluorobutane-1,3,3-triol (yield from 1,1,1,3,3,3-hexafluoro-2-propanol was 80%)
Reaction SMILES: [N-:1]=[N+:2]=[N-:3].[Na+].Br[C@@H:6]1[CH2:25][N:9]2[C:10](=[O:24])[N:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[CH2:12][C@@H:8]2[CH2:7]1.O>CN(C=O)C>[N:1]([C@H:6]1[CH2:25][N:9]2[C:10](=[O:24])[N:11]([C:13]3[CH:18]=[CH:17][C:16]([O:19][C:20]([F:23])([F:22])[F:21])=[CH:15][CH:14]=3)[CH2:12][C@@H:8]2[CH2:7]1)=[N+:2]=[N-:3]
Reactant: O=C1N(c2ccc(OC(F)(F)F)cc2)C[C@@H]2C[C@H](Br)CN12
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: [N-]=[N+]=N[C@@H]1C[C@H]2CN(c3ccc(OC(F)(F)F)cc3)C(=O)N2C1
Temperature: 70 °C
Reaction time: 2 h
Yield: 79.4 %

Procedure:
Sodium azide (80 mg, 1.2 mmol) was added to a solution of (6S,7aS)-6-Bromo-2-(4-trifluoromethoxy-phenyl)-hexahydro-pyrrolo[1,2-c]imidazol-3-one (350 mg, 1.0 mmol) in anhydrous DMF (10 mL), the mixture was heated to 70° C. and stirred for 2 hours. The mixture was cooled and poured into water (30 mL), extracted with ethyl acetate (3×20 mL), the organic layers was combined and washed with water (2×20 mL), brine (20 mL), dried over anhydrous sodium sulphate, filtered and concentrated. The residue was purified by silica gel column chromatography (eluting with petroleum ether/ethyl acetate=10:1) to give 260 mg (83%) of the title compound. 1H NMR (300 MHz, CDCl3): δ 7.59 (d, 2H, J=9.3 Hz), 7.19 (d, 2H, J=8.4 Hz), 4.33 (t, 1H, J=6.3 Hz), 4.13-3.98 (m, 3H), 3.75-3.72 (m, 1H), 3.15 (dd, 1H, J1=12.6 Hz, J2=2.1 Hz), 2.19 (dd, 1H, J1=13.2 Hz, J2=3.9 Hz), 1.73-1.63 (m, 1H).
Reaction SMILES: [S:1](Cl)([CH3:4])(=[O:3])=[O:2].[CH3:6][O:7][N:8]=[C:9]1[CH2:13][C@@H:12]([CH2:14][OH:15])[N:11]([C:16]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)=[O:17])[CH2:10]1>C(Cl)Cl>[CH3:4][S:1]([O:15][CH2:14][C@@H:12]1[CH2:13][C:9](=[N:8][O:7][CH3:6])[CH2:10][N:11]1[C:16]([C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[CH:20][CH:19]=1)=[O:17])(=[O:3])=[O:2]
Reactant: CS(=O)(=O)Cl
Reactant: CON=C1C[C@@H](CO)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Solvent: ClCCl
Product: CON=C1C[C@@H](COS(C)(=O)=O)N(C(=O)c2ccc(-c3ccccc3)cc2)C1
Temperature: 0 °C

Procedure:
Mesyl chlorid (48 μl, 0.62 mmol) was added to a solution of alcohol (2) (EZ mixture, 80 mg, 0.25 mmol) in DCM (8 ml) cooled at 0° C. and maintained under nitrogen atmosphere. The reaction mixture was then allowed to warm to r.t. and monitored by tlc. Completion was achieved after 1 h30. Organic phase was washed with saturated ammonium chlorid solution and brine, dried over magnesium sulfate, filtered and concentrated.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:17]2C=C[C:20]([O:23]C)=[C:19](OC)[CH:18]=2)=[CH:12][C:13](OC)=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].COC1C=C(C=CC=1OC)C(C1OC=CC=1)=O.C(OP(CC#[N:54])(=O)OCC)C.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]([C:17]2[O:23][CH:20]=[CH:19][CH:18]=2)=[CH:12][C:13]#[N:54])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]
Reactant: COC(=O)C=C(c1ccc(OC)c(OC)c1)c1ccc(OC)c(OC)c1
Reactant: CCOP(=O)(CC#N)OCC
Agent: COc1ccc(C(=O)c2ccco2)cc1OC
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Product: COc1ccc(C(=CC#N)c2ccco2)cc1OC

Procedure:
3-(3,4-Dimethoxyphenyl)-3-(2-furyl)acrylonitrile was prepared analogously to methyl 3,3-bis-(3′,4′-dimethoxyphenyl)acrylate using 2-(3,4-dimethoxybenzoyl)furane (0.87 g, 4 mmol), diethylcyanomethylphosphonate (0.73 mL, 4.4 mmol) and lithium hexamethyldisilazide (3.4 mL, 4.4 mmol, 1.3M) with a reaction time of 3 hours at room temperature. The crude product was purified by chromatography (silica gel, 2% ethyl acetate/methylene chloride) to afford 0.78 g (76%) of a mixture of the E and Z isomers as an off white solid: mp 78-82° C.; 1H NMR (CDCl3) δ7.68-7.73 (m, 2 H), 7.16-6.75 (m, 7 H), 6.54-6.39 (m, 3 H), 5.87 (s, 1 H), 5.30 (s, 1 H), 3.93 (s, 3 H), 3.93 (s, 3 H), 3.91 (s, 3 H), 3.88 (s, 3 H); 13C NMR (CDCl3) δ152.0, 150.7, 150.5, 150.4, 149.3, 148.8, 148.7, 148.7, 145.2, 145.0, 129.6, 126.7, 122.1, 121.6, 118.1, 118.0, 116.5, 115.6, 112.5, 112.1, 112.0, 111.5, 110.9, 110.8, 90.5, 90.2, 55.9, 55.9, 55.9, 55.8; Anal. Calcd for C15H13NO3. Theoretical: C, 70.58; H, 5.13; N, 5.49. Found: C, 70.61;H, 5.09; N, 5.18.
Reaction SMILES: [CH:1]([NH:4][C:5]1[C:10]([C:11](O)=[O:12])=[CH:9][N:8]=[C:7]([S:14][CH3:15])[N:6]=1)([CH3:3])[CH3:2].S(Cl)([Cl:18])=O>>[CH:1]([NH:4][C:5]1[C:10]([C:11]([Cl:18])=[O:12])=[CH:9][N:8]=[C:7]([S:14][CH3:15])[N:6]=1)([CH3:3])[CH3:2]
Reactant: O=S(Cl)Cl
Reactant: CSc1ncc(C(=O)O)c(NC(C)C)n1
Product: CSc1ncc(C(=O)Cl)c(NC(C)C)n1
Temperature: 50 °C

Procedure:
To 3.5 (15.4 mmol) of 4-(isopropylamino)-2-(methylthio)pyrimidine-5-carboxylic acid is added 9.0 mL (123.2 mmol) of thionyl chloride, and the reaction mixture is heated at 50° C. for 1 hour, cooled to room temperature, and concentrated. The residue is twice suspended in anhydrous toluene and concentrated to give a colorless solid, 4-(isopropylamino)-2-(methylthio) pyrimidine-5-carboxylic acid chloride.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH2:6].C(N(CC)CC)C.[C:17](Cl)(=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[CH2:5][NH:6][C:17](=[O:24])[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1
Reactant: NCc1cccc(Br)c1
Reactant: O=C(Cl)c1ccccc1
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C(NCc1cccc(Br)c1)c1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 100.3 %

Procedure:
7 g (31.6 mmol) of 3-bromobenzylamine, 100 ml of THF and 9.6 ml (69.2 mmol) of triethylamine are placed in a three-necked flask under a stream of nitrogen. 4 ml (34.6 mmol) of benzoyl chloride are added dropwise and the mixture is stirred for 1 hour at room temperature. The reaction medium is extracted with ethyl acetate, washed with water, dried over magnesium sulfate, filtered and evaporated. 9.2 g (100%) of the desired product are obtained.
Reaction SMILES: [C:1]([N:4]1[C:8]([C:9](=O)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[C:7]([CH2:19][CH3:20])[N:6]([C:21](=[O:23])[CH3:22])[C:5]1=[O:24])(=[O:3])[CH3:2].[S:25]([O-])([O-])(=O)=O.S(O)(O)(=O)=O.S(O)(O)(=O)=O.S(O)(O)(=O)=O.S(O)([O-])(=O)=O.[P+3]>C1(C)C=CC=CC=1>[C:1]([N:4]1[C:8]([C:9](=[S:25])[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[O:16][CH3:17])=[C:7]([CH2:19][CH3:20])[N:6]([C:21](=[O:23])[CH3:22])[C:5]1=[O:24])(=[O:3])[CH3:2]
Reactant: O=S(=O)([O-])[O-]
Reactant: CCc1c(C(=O)c2ccccc2OC)n(C(C)=O)c(=O)n1C(C)=O
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])O
Agent: [P+3]
Solvent: Cc1ccccc1
Product: CCc1c(C(=S)c2ccccc2OC)n(C(C)=O)c(=O)n1C(C)=O

Procedure:
In 100 ml Toluene are suspended 10 g of 1,3-diacetyl-1,3-dihydro-4-ethyl-5-(2-methoxybenzoyl)-2H-imidazole-2-one and 20 g phosphorus pentasulfate. The mixture is refluxed 6 hours and the solvent evaporated to yield the title compound.
Reaction SMILES: [Cl:1][C:2]1[CH:8]=[CH:7][C:5]([OH:6])=[CH:4][C:3]=1[OH:9].[C:10]([CH2:12][CH2:13][CH2:14][O:15][C:16]1[CH:17]=[C:18]([CH2:22][C:23]([OH:25])=O)[CH:19]=[CH:20][CH:21]=1)#[N:11].P(Cl)(Cl)(Cl)(Cl)Cl.[CH3:32]N(C=O)C>>[Cl:1][C:2]1[CH:8]=[C:7]2[C:5](=[CH:4][C:3]=1[OH:9])[O:6][CH:32]=[C:22]([C:18]1[CH:17]=[C:16]([CH:21]=[CH:20][CH:19]=1)[O:15][CH2:14][CH2:13][CH2:12][C:10]#[N:11])[C:23]2=[O:25]
Reactant: CN(C)C=O
Reactant: N#CCCCOc1cccc(CC(=O)O)c1
Reactant: Oc1ccc(Cl)c(O)c1
Agent: ClP(Cl)(Cl)(Cl)Cl
Product: N#CCCCOc1cccc(-c2coc3cc(O)c(Cl)cc3c2=O)c1

Procedure:
This compounds was synthesised in the same manner as described above. 4-Chlororesorcinol (0.33 g, 2.28 mmol), [3-(3-Cyano-propoxy)-phenyl]-acetic acid (0.5 g, 2.28 mmol), BF3Et2O (5 ml), PCl5 (0.71 g, 3.4 mmol), DMF (8 ml and 5 ml). Crude 4-[3-(6-Chloro-7-hydroxy-4-oxo-4H-chromen-3-yl)-phenoxy]-butyronitrile was obtained as an oil which was taken onto the next stage without further purification.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=2)[CH:6]=[CH:5][C:4]=1[NH:15][CH:16]=O.[H-].[Na+].[Cl:20][C:21]1[C:26]2[N:27]=C(S(C)(=O)=O)[N:29]=[CH:30][C:25]=2[CH:24]=[CH:23][N:22]=1.[OH-].[Na+]>C1COCC1.CO>[Cl:20][C:21]1[C:26]2[N:27]=[C:16]([NH:15][C:4]3[CH:5]=[CH:6][C:7]([C:9]4[CH:10]=[N:11][N:12]([CH3:14])[CH:13]=4)=[CH:8][C:3]=3[O:2][CH3:1])[N:29]=[CH:30][C:25]=2[CH:24]=[CH:23][N:22]=1
Reactant: CS(=O)(=O)c1ncc2ccnc(Cl)c2n1
Reactant: COc1cc(-c2cnn(C)c2)ccc1NC=O
Agent: [H-]
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: C1CCOC1
Product: COc1cc(-c2cnn(C)c2)ccc1Nc1ncc2ccnc(Cl)c2n1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 78.6 %

Procedure:
A solution of N-(2-methoxy-4-(1-methyl-1H-pyrazol-4-yl)phenyl)formamide (Preparation 56, 24 mg, 0.104 mmol) in THF (1 mL) was treated with sodium hydride (7 mg, 0.175 mmol) at 0° C. After stirring for 20 minutes at room temperature the mixture was cooled to 0° C. and 8-chloro-2-(methylsulfonyl)pyrido[3,4-d]pyrimidine (Preparation 97, 33 mg, 0.135 mmol) was added. The reaction was allowed to reach room temperature and stirred for 18 hours. Aqueous NaOH (2M, 0.5 mL) and MeOH (0.5 mL) were added and the resulting mixture stirred for 1 hour. The volatiles were removed under reduced pressure and the residue was partitioned between EtOAc and water. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with water, brine, dried and concentrated. The residue was purified by silica gel column chromatography eluting with 0 to 80% EtOAc in cyclohexane to give the title compound (30 mg, 79%).
Reaction SMILES: [CH:1](=[CH:10][C:11]([OH:13])=O)[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.S(Cl)([Cl:16])=O>C1C=CC=CC=1>[CH:1](=[CH:10][C:11]([Cl:16])=[O:13])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)C=CC=Cc1ccccc1
Solvent: c1ccccc1
Product: O=C(Cl)C=CC=Cc1ccccc1
Yield: 94 %

Procedure:
8.7 g of cinnamylideneacetic acid was added to 100 ml of benzene and then an excessive amount of thionyl chloride (1.2 molar equivalent to cinnamylideneacetic acid) was added dropwise to the mixture while heating to 70°-90°C and stirring the mixture to form a cinnamylideneacetic acid chloride. By distilling off the solvent from the reaction product, yellow crystals having a melting point of about 60°C were obtained. The crystals were dissolved in 20 ml of methyl ethyl ketone and then 8 g of hydroxyethyl methacrylate was added slowly to the solution with stirring under ice-cooling. After further stirring under ice-cooling for about 20 minutes, 50 ml of pyridine was added slowly to the mixture as a hydrogen chloride accepting agent to conduct esterification. When the reaction product was treated with diluted (5%) hydrochloric acid, crystals were formed, which were recovered and recrystallized from hexane to provide crystals of a monomer having a melting point of 51° - 52.5°C with a yield of 94%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([N:14]3[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]3)=[O:13])[C:6]=2[CH:21]=1.[C:22]1(=[O:28])[O:27][C:25](=[O:26])[CH2:24][CH2:23]1>N1C=CC=CC=1.O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([N:14]3[CH2:15][CH2:16][CH:17]([O:20][C:22]([CH2:23][CH2:24][C:25]([OH:27])=[O:26])=[O:28])[CH2:18][CH2:19]3)=[O:13])[C:6]=2[CH:21]=1
Reactant: O=C1CCC(=O)O1
Reactant: O=C(Cn1c(=O)sc2ccc(Cl)cc21)N1CCC(O)CC1
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: O=C(O)CCC(=O)OC1CCN(C(=O)Cn2c(=O)sc3ccc(Cl)cc32)CC1
Reaction time: 8 h
Yield: 59.8 %

Procedure:
A solution of 5-chloro-3-(4-hydroxypiperidinocarbonylmethyl)benzothiazolin-2-one (3.2 g) in dry pyridine (2.5 ml) and dry tetrahydrofuran (50 ml) was cooled. To the solution was dropwise added a solution of succinic anhydride (1.1 g) in dry tetrahydrofuran (5 ml) under stirring. The mixture was refluxed for 2 hours and then left overnight. The reaction mixture was treated in the same manner as that in Example 6 to yield the title compound as colorless crystals (2.5 g).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]#[N:14])[N:8]=2)=[CH:4][CH:3]=1.[CH3:17][O-:18].[Na+]>>[Cl:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][C:7]2[N:8]=[C:9]([C:13](=[NH:14])[O:18][CH3:17])[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1
Reactant: N#Cc1cccc(Cc2ccc(Cl)cc2)n1
Reactant: C[O-]
Agent: [Na+]
Product: COC(=N)c1cccc(Cc2ccc(Cl)cc2)n1
Temperature: 20 °C
Reaction time: 17 h
Yield: 130.9 %

Procedure:
2-p-Chlorobenzyl-6-cyanopyridine (1.69 g, 0.0074 moles) was added to a solution of sodium methoxide [prepared by dissolving sodium metal (0.19 g, 0.0081 gram atoms) in methanol (20 ml)] under nitrogen, and the mixture stirred at 20° C. for 17 hours. The methanol was evaporated, the residue taken up in chloroform, neutralised with acetic acid and the precipitate filtered off on HYFLO. Concentration of the filtrate gave methyl 6-p-chlorobenzyl-2-picoline imidate (1.20 g, 62%) which was used in the next stage without further purification.
Reaction SMILES: [C:1]([C:3](=[C:8]1[CH2:12][CH2:11][S:10][CH2:9]1)[C:4]([O:6][CH3:7])=[O:5])#[N:2].S(Cl)(Cl)(=O)=O.N1C=CC=CC=1>C(Cl)Cl>[C:1]([CH:3]([C:8]1[CH:12]=[CH:11][S:10][CH:9]=1)[C:4]([O:6][CH3:7])=[O:5])#[N:2]
Reactant: COC(=O)C(C#N)=C1CCSC1
Solvent: ClCCl
Solvent: O=S(=O)(Cl)Cl
Solvent: c1ccncc1
Product: COC(=O)C(C#N)c1ccsc1
Reaction time: 0.25 h
Yield: 94.4 %

Procedure:
A solution of 5.00 g (27.3 mmol) of methyl 2-cyano-2-(3-tetrahydrothienylidene)acetate in 100 ml of methylene chloride was cooled to +5° under nitrogen and 3.70 g (27.3 mmol) of sulfuryl chloride in 5 ml of methylene chloride was added all at once. After 15 min. at +5° the solution was purged with a vigorous stream of nitrogen for 5 min. Pyridine (4.0 g, 50 mmol, 1.83 eq.) was added and the solution was brought to room temperature with a water bath. After 30 min. the reaction was quenched with 30 ml of 1 M H2SO4 and 70 ml of water. The mixture was stirred to 15 min. and the organic phase was separated. The aqueous phase was extracted with 30 ml of methylene chloride and the combined organic layers were dried by passing them through a cone of anhydrous calcium sulfate. Solvent was removed to yield an orange oil homogeneous by tlc and glc (SE-30, SP2300). Bulb to bulb distillation (about 120°/0.5 torr) yielded 4.67 g (94.5%) of methyl 2-cyano-2(3-thienyl)acetate as an analytically pure pale yellow oil, bp 108°-110°/0.5 torr, (lit. 107°-9°/0.95 torr). IR (film) 4.42 (w), 5.73 (s), 6.98 (m), 8.00 (s), 9.86 (m), 12.95 (s); NMR (CDCl3) 7.6-7.4 (m, 2H), 7.3-7.1 (d×d, J=2, 5 Hz, 1H), 5.00 (s, 1H), 3.90 (s, 3H), UV max=234 nm. 13C NMR (CDCl3) 165.0, 129.1, 127.5, 126.6, 124.7, 115.5, 53.9, 38.9.
Reaction SMILES: [CH3:1][C:2]1[C@:8]([OH:17])(/[CH:9]=[CH:10]/[C:11](/[CH3:16])=[CH:12]\[C:13]([OH:15])=[O:14])[C:7]([CH3:19])([CH3:18])[CH2:6][C:4](=[O:5])[CH:3]=1.[CH3:20][N:21]([CH3:23])[CH3:22].CC1C(O)(/C=C/C(/C)=C\C(O)=O)C(C)(C)CC(=O)C=1.C([O-])(=O)/C=C/C=C/C.[K+]>O>[CH3:1][C:2]1[C:8]([OH:17])(/[CH:9]=[CH:10]/[C:11](/[CH3:16])=[CH:12]\[C:13]([OH:15])=[O:14])[C:7]([CH3:19])([CH3:18])[CH2:6][C:4](=[O:5])[CH:3]=1.[CH3:20][NH+:21]([CH3:23])[CH3:22]
Reactant: CC1=CC(=O)CC(C)(C)[C@@]1(O)/C=C/C(C)=C\C(=O)O
Reactant: CN(C)C
Agent: C/C=C/C=C/C(=O)[O-]
Agent: CC1=CC(=O)CC(C)(C)C1(O)/C=C/C(C)=C\C(=O)O
Agent: [K+]
Solvent: O
Product: C[NH+](C)C

Procedure:
(S)-(+)-Abscisic acid (2.64 g of 95% purity) was suspended in 15 mL of deionized water containing 50 mg of Tween 20. An aqueous solution of trimethylamine (1.5 mL of 6.6M concentration) was added, which caused most of the abscisic acid to dissolve. The remainder of the neutralization was then carried out by careful dropwise addition of the aqueous trimethylamine, to give a clear solution of pH 6.8. Preservative (63 mg of potassium sorbate) was added, and it quickly dissolved. The solution was made up to 25 mL final volume to give a 10% by weight aqueous composition of abscisic acid as a trimethylammonium salt.
Reaction SMILES: [C:1]1([CH3:11])C(S(O)(=O)=O)=CC=CC=1.[NH2:12][C@H:13]1[C@H:17]([OH:18])[CH2:16][CH:15]=[CH:14]1.[C:19](=[O:22])([O-])[O-:20].[Na+].[Na+].[Cl:25][C:26]([Cl:33])([Cl:32])[CH2:27]OC(Cl)=O>O>[NH2:12][C@H:13]1[C@H:17]([OH:18])[CH2:16][CH:15]=[CH:14]1.[Cl:25][C:26]([Cl:33])([Cl:32])[CH2:27][NH:12][C:19]([O:20][CH2:1][CH3:11])=[O:22]
Reactant: O=C([O-])[O-]
Reactant: Cc1ccccc1S(=O)(=O)O
Reactant: O=C(Cl)OCC(Cl)(Cl)Cl
Agent: N[C@@H]1C=CC[C@H]1O
Agent: [Na+]
Solvent: O
Product: CCOC(=O)NCC(Cl)(Cl)Cl

Procedure:
A 13.55 g. (50 mM) trans-3-amino-4-hydroxycyclopentene toluenesulfonate is dissolved in 75 ml. of water. The solution treated with 10.6 g. (10.0 mM) of sodium carbonate, cooled in an ice bath, and treated dropwise with 10.6 g. (50 mM) of trichloroethylchloroformate while stirring vigorously. After 75 min. the reaction is partitioned between water and methylene chloride. The aqueous layer is separated and extracted two times more with methylene chloride. The combined methylene chloride layer is dried over sodium sulfate and concentrated in vacuo. Crystals of trans-3-amino-4-hydroxy-cyclopentene-N-trichloroethyl urethane are formed during the concentration. These are collected three times, each time rinsing the crystals with ether crop 1, 6.12 g. m.p. 105°-106°; crop 2, 4.35 g., m.p. 105-106; crop 3, 1.28 g., m.p. 104°-105°.
Reaction SMILES: [CH:1]1[C:14]2[C:5](=[N:6][CH:7]=[C:8]3[C:13]=2[CH:12]=[CH:11][CH:10]=[CH:9]3)[CH:4]=[CH:3][CH:2]=1.[C:15](Cl)(=[O:19])[CH:16]([CH3:18])[CH3:17].[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[CH:23]=[CH:22]1>>[NH:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:23]([CH:7]2[C:8]3[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:14]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[N:6]2[C:15](=[O:19])[CH:16]([CH3:18])[CH3:17])=[CH:22]1
Reactant: CC(C)C(=O)Cl
Reactant: c1ccc2c(c1)cnc1ccccc12
Reactant: c1ccc2[nH]ccc2c1
Product: CC(C)C(=O)N1c2ccccc2-c2ccccc2C1c1c[nH]c2ccccc12

Procedure:
1-[6-(1H-Indol-3-yl)-6H-phenanthridin-5-yl]-2-methyl-propan-1-one was prepared from phenanthridine, isobutyryl chloride, and indole according to GP 2. Yield, 18%. (+)-ESI-MS: m/z=367 [M+H]+, 250 [M-indole+H]+, 180.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:15])[C:4](=[N+]=[N-])[C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[CH:6]=1.[CH:16]1([OH:22])[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1.O>ClCCl.CC(O)=O.CC(O)=O.CC(O)=O.CC(O)=O.[Rh].[Rh]>[CH3:1][O:2][C:3](=[O:15])[CH:4]([O:22][CH:16]1[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]1)[C:5]1[CH:10]=[CH:9][C:8]([Cl:11])=[C:7]([Cl:12])[CH:6]=1
Reactant: OC1CCCCC1
Reactant: COC(=O)C(=[N+]=[N-])c1ccc(Cl)c(Cl)c1
Agent: [Rh]
Solvent: O
Solvent: ClCCl
Solvent: CC(=O)O
Product: COC(=O)C(OC1CCCCC1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.2 %

Procedure:
In a dry 25 mL round bottom flask under argon was placed diazo-(3,4-dichloro-phenyl)-acetic acid methyl ester (from Example 1, 550 mg 2.24 mmol) and cyclohexanol (0.47 mL, 4.49 mmol) in dichloromethane (10 mL). The solution was stirred at 25° C. and as rhodium (II) acetate dimer (20 mg, 0.045 mmol) was added, the immediate evolution of gas was observed and the color changed from bright yellow to an aquagreen color. After the solution was stirred at 25° C. for 1 h, it was poured into water and the layers were separated. The aqueous layer was washed with dichloromethane (3×15 mL) and the combined organic layers were dried over sodium sulfate and evaporated under reduced pressure. The residual oil was purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 98/2 hexanes/ethyl acetate) to furnish rac-cyclohexyloxy-(3,4-dichloro-phenyl)-acetic acid methyl ester (527 mg, 74% yield) as a clear colorless oil: EI-HRMS m/e calcd for C15H18Cl2O3 (M+) 316.0633, found 316.0646.
Reaction SMILES: [CH3:1][Mg]Br.[CH:4]([C:6]1[N:10]([CH3:11])[CH:9]=[N:8][CH:7]=1)=[O:5].O>C(OCC)C.C1COCC1>[OH:5][CH:4]([C:6]1[N:10]([CH3:11])[CH:9]=[N:8][CH:7]=1)[CH3:1]
Reactant: C[Mg]Br
Reactant: Cn1cncc1C=O
Solvent: CCOCC
Solvent: O
Solvent: C1CCOC1
Product: CC(O)c1cncn1C
Temperature: -20 °C
Yield: 88 %

Procedure:
Methyl magnesium bromide (100 ml of a 3M solution in diethyl ether, 0.30 mol) was added dropwise to a solution of 5-formyl-1-methylimidazole (14.5 g, 0.13 mol) in THF (750 ml) cooled to −20° C. such that the reaction temperature was kept below 3° C. The mixture was allowed to warm to ambient temperature and water (150 ml) was carefully added. The aqueous mixture was continuously extracted with EtOAc. The EtOAc extract was dried, and the volatiles removed by evaporation to give the title compound 14.4 g, (88%) as a solid product. NMR: 1.41 (d, 3H), 4.65-4.77 (m, 1H), 4.96-5.11 (m, 1H), 6.72 (s, 1H), 7.47 (s, 1H).