Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O:1]1[C:5]2[C:6]([O:10][CH2:11][CH2:12]Cl)=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[F:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][CH:19]=[C:18]2[CH2:24][CH2:25][CH2:26][NH2:27].C(N(CC)CC)C.O>CS(C)=O>[O:1]1[C:5]2[C:6]([O:10][CH2:11][CH2:12][NH:27][CH2:26][CH2:25][CH2:24][C:18]3[C:17]4[C:21](=[CH:22][CH:23]=[C:15]([F:14])[CH:16]=4)[NH:20][CH:19]=3)=[CH:7][CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1
Reactant: NCCCc1c[nH]c2ccc(F)cc12
Reactant: ClCCOc1cccc2ccoc12
Solvent: CCN(CC)CC
Solvent: O
Solvent: CS(C)=O
Product: Fc1ccc2[nH]cc(CCCNCCOc3cccc4ccoc34)c2c1
Temperature: 90 °C
Reaction time: 12 h
Yield: 30.3 %

Procedure:
A solution of 2-(benzofuran-7-yloxy)-ethylchloride (0.58 g, 2.9 mmol), 3-(5-fluoro-1H-indol-3-yl)propylamine (1.4 g, 7.4 mmol) and triethylamine (0.74 g, 7.4 mmol) in anhydrous DMSO (20 ml) was allowed to stir at 90° C. for 12 hours. The mixture was poured into water (100 ml) and extracted with methylene chloride (3×100 ml). The organic layer was washed with water (3×150 ml), dried over anhydrous sodium sulfate, filtered and the solvent was removed under vacuum. Chromatography (7% methanol-methylene chloride) afforded 0.31 g (30%) of product as a light-brown oil.
Reaction SMILES: [C:1]([NH2:4])(=[O:3])[CH3:2].[Cl-].[Cs+].[O:7]=[CH:8][C@@H:9]([C@H:11]([C@@H:13]([C@@H:15]([CH2:17][OH:18])[OH:16])[OH:14])[OH:12])[OH:10].OP([O-])(O)=O.[K+]>>[OH:18][CH2:17][C@@H:15]([C@H:13]([C@@H:11]([C@@H:9]([CH2:8][OH:7])[OH:10])[OH:12])[OH:14])[OH:16].[C:1]([NH2:4])(=[O:3])[CH3:2]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: CC(N)=O
Agent: O=P([O-])(O)O
Agent: [Cl-]
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO
Temperature: 55 °C
Reaction time: 0.17 h

Procedure:
Acetamide (Aldrich 99% sublimed)—0.6 g/L; CsCl—1.68 g/L; Glucose—20 g/L; KH2PO4—20 g/L; MgSO4.7H2O—0.6 g/L; CaCl2.2H2O—0.6 g/L; 1000× salts (see below)—1 ml. pH adjusted to 5.5 and volume brought to 300 ml. Filter sterilized with 0.22 micron filter and warmed to 55° C. in an oven. To 700 ml water Noble Agar (low-melt for top agar) 20 g and Sorbitol 218 g was added and then autoclaved. This mixture was cooled to 55° C., and filter sterilized, acetamide mix was added. Plates or tubes were poured. 1000× Salts—FeSO4.7H2O (0.5 g/100 ml); MnSO4.H2O (0.16 g/100 ml); ZnSO4.7H2O (0.14 g/100 ml); CoCl2.6H2O (0.1 g/100 ml) and filter sterilize with 0.22 micron filter. Potato Dextrose Agar (PDA Difco Dehydrated Culture Media)—Potatoes, infusion from 200 g/L; Dextrose, 20 g/L and Agar, 15 g/L were mixed well in 50-80% final volume of dH2O, and then brought to 100% final volume. This mixture was autoclaved, cooled to 55° C. and poured. To make up 1% skim milk agar for a pH 3.5 media PDA was prepared as above and to 100 ml molten PDA, 1.8 ml 10% tartaric acid and 12.5 ml sterilized 8% skim milk was added and plates were poured. To pre-sterilize skim milk, 8% skim milk (Difco) was autoclaved for 10 minutes, 122-123° C., and chamber pressure during exposure of 32-35 psi. The mixture was removed, cooled and stored at room temperature.
Reaction SMILES: [C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5].C=C(OP(O)(O)=O)C(O)=O.C(CC([O-])=O)(C(O)=O)=O.C([O-])(=O)C(CC([O-])=O)O.C([O-])(=O)C=O.[O:42]=[CH:43][C@@H:44]([C@H:46]([C@@H:48]([C@@H:50]([CH2:52][OH:53])[OH:51])[OH:49])[OH:47])[OH:45]>>[OH:53][CH2:52][C@@H:50]([C@H:48]([C@@H:46]([C@@H:44]([CH2:43][OH:42])[OH:45])[OH:47])[OH:49])[OH:51].[C:1]([OH:8])(=[O:7])[CH2:2][CH2:3][C:4]([OH:6])=[O:5]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Agent: C=C(OP(=O)(O)O)C(=O)O
Agent: O=C(O)CCC(=O)O
Agent: O=C([O-])CC(=O)C(=O)O
Product: OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)CO

Procedure:
Metabolic flux analysis was used to evaluate the effect of different carbon sources on succinic acid production in batch fermentations with A. succinogenes FZ45. The analyses established that the major pathway for succinic acid production in A. succinogenes FZ45 flows in the following manner: phosphoenolpyruvate (PEP→*oxaloacetate (OAA)→malate→fumarate→succinic acid. The glyoxylate shunt and the PEP-transport-system (PTS) appear not to be substantially used in the organism. Glucose fermentations reach a concentration of 61.7 g/L succinic acid with a yield of about 94% (succinic acid (g)/glucose (g)). Fermentations performed using a more reduced carbon source, such as sorbitol, produced higher amounts of succinic acid (77.3 g/L) with a higher yield (108% succinic acid (g)/glucose (g)), indicating that reducing power may become a limiting factor during the fermentation of glucose.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=O)[CH:2]=1.C(O)(=O)[CH2:14][C:15]([OH:17])=[O:16].N1CCCCC1.Cl>O.N1C=CC=CC=1>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[C:3]([CH:11]=[CH:14][C:15]([OH:17])=[O:16])[CH:2]=1
Reactant: O=Cc1cnc2ccccc2c1
Reactant: O=C(O)CC(=O)O
Agent: Cl
Solvent: O
Solvent: C1CCNCC1
Solvent: c1ccncc1
Product: O=C(O)C=Cc1cnc2ccccc2c1
Temperature: 100 °C
Reaction time: 3 h
Yield: 94.7 %

Procedure:
80 g of 3-quinoline carboxaldehyde, 85 g of malonic acid and 6.50 g of piperidine were added to 350 ml of pyridine, and stirred at 100° C. for 3 hours. After mixing with 1000 ml of distilled water, concentrated HCl was added thereto until pH of the solution became 4.8, and stirred for 1 hour. The resulting solid was filtrated under a reduced pressure, washed with 1500 ml of distilled water, and dried for 15 to 40 hours to obtain 96 g of the title compound as a white solid (yield 95%).
Reaction SMILES: [CH3:1][CH:2]([CH2:4][CH2:5][CH2:6][C@H:7]([CH2:9][CH2:10][CH2:11][C@H:12]([CH2:14][CH2:15][CH2:16]/[C:17](=[CH:19]/[CH2:20][OH:21])/[CH3:18])[CH3:13])[CH3:8])[CH3:3].[H][H]>[Ni]>[CH2:20]([OH:21])[CH2:19][CH:17]([CH2:16][CH2:15][CH2:14][CH:12]([CH2:11][CH2:10][CH2:9][CH:7]([CH2:6][CH2:5][CH2:4][CH:2]([CH3:3])[CH3:1])[CH3:8])[CH3:13])[CH3:18]
Reactant: C/C(=C\CO)CCC[C@H](C)CCC[C@H](C)CCCC(C)C
Reactant: [H][H]
Agent: [Ni]
Product: CC(C)CCCC(C)CCCC(C)CCCC(C)CCO

Procedure:
Hydrogenation of phytol can also be accomplished using Raney nickel and hydrogen to yield phytanol as referenced in Bendavid, A., Burns, C. J., Leslie, D. F., Hashimoto, K., Ridley, D. D., Sandanayake, S., and Wieczorek L., J. Org. Chem. (2001), 66, 3709-3716; Kim, T., Chan, K. C, and Crooks, R. M., J. Am. Chem. Soc. (1997) 119, 189; and Jellum, E., Eldjarn, L., and Try, K., Acta Chem. Scand. (1966), 20, 2335.
Reaction SMILES: O1CCCC1.[H-].C([Al+]CC(C)C)C(C)C.CON(C)[C:19]([C:21]1[N:22]=[CH:23][C:24]2[C:29]([CH:30]=1)=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:20]>CCCCCCC>[CH:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:30]=[C:21]([CH:19]=[O:20])[N:22]=1
Reactant: CON(C)C(=O)c1cc2ccccc2cn1
Agent: CC(C)C[Al+]CC(C)C
Agent: [H-]
Solvent: CCCCCCC
Solvent: C1CCOC1
Product: O=Cc1cc2ccccc2cn1
Temperature: -78 °C

Procedure:
In 5 mL dry tetrahydrofuran 0.11 g (0.52 mmol) of isoquinoline-3-carboxylic acid methoxy-methyl-amide was dissolved, and cooled down to −78° C. under the atmosphere of nitrogen. 0.57 mL of 1M diisobutylaluminum hydride solution in heptane was added slowly. After the addition was complete, the solution was allowed to warm up to 0° C. over 2 hours and was quenched with ethyl acetate, and water was added, and extracted with dichloromethane. The organic solution was dried with anhydrous magnesium sulfate and evaporated in vacuum to give 60 mg of the crude aldehyde, which was used in the following steps without purification. LC-MSD, m/z for C10H7NO [M+H]+: 158.3.
Reaction SMILES: [CH3:1][C@H:2]1[CH2:7][CH2:6][CH2:5][CH2:4][N:3]1[C:8](Cl)=[O:9].[F:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][NH2:19])=[N:16][CH:17]=1.CCN(C(C)C)C(C)C.O>C(Cl)Cl.CCOCC.CCCCC>[F:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][NH:19][C:8]([N:3]2[CH2:4][CH2:5][CH2:6][CH2:7][C@@H:2]2[CH3:1])=[O:9])=[N:16][CH:17]=1
Reactant: C[C@H]1CCCCN1C(=O)Cl
Reactant: NNc1ccc(F)cn1
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Solvent: CCCCC
Product: C[C@H]1CCCCN1C(=O)NNc1ccc(F)cn1
Temperature: 25 °C
Reaction time: 96 h
Yield: 77.8 %

Procedure:
A stirred solution of Intermediate 2b (17.20 g, assumed to be 95.49 mmol) and (5-fluoro-pyridin-2-yl)-hydrazine (12.14 g, 95.51 mmol) in DCM (300 mL) at RT was treated with DIPEA (34 mL, 195.18 mmol) during 5 min. This mixture was continued to be stirred at RT for 4 days before being added to water (500 mL) and phases separated. The aqueous layer was further extracted into DCM (4×100 mL), combined extracts washed with brine, dried (MgSO4), passed through a phase separation cartridge and concentrated in vacuo to give a residual solid. This product was treated with Et2O-pentane and the resultant solids filtered off and dried to give Intermediate 2c (18.74 g, 77%). LCMS (Method 3) Rt 2.26 min, m/z 253 [MH+]. 1H NMR (300 MHz, CDCl3): 1.23 (3H, d, J 6.9), 1.40-1.74 (6H, m), 2.97 (1H, td, J 13.1, 3.0), 3.82-3.91 (1H, m), 4.27-4.38 (1H, m), 6.54 (1H, s), 6.78 (1H, ddd, J 9.1, 3.7, 0.6), 7.30 (1H, ddd, J 9.1, 7.8, 2.9), 8.00 (1H, d, J 2.6).
Reaction SMILES: [Cl-].[Al+3].[Cl-].[Cl-].[N+:5]([C:8]1[CH:16]=[CH:15][C:11]([C:12](Cl)=[O:13])=[CH:10][CH:9]=1)([O-:7])=[O:6].[C:17]1([O:23][CH3:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>[N+](C1C=CC=CC=1)([O-])=O>[CH3:24][O:23][C:17]1[CH:22]=[CH:21][C:20]([C:12]([C:11]2[CH:15]=[CH:16][C:8]([N+:5]([O-:7])=[O:6])=[CH:9][CH:10]=2)=[O:13])=[CH:19][CH:18]=1
Reactant: COc1ccccc1
Reactant: O=C(Cl)c1ccc([N+](=O)[O-])cc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: O=[N+]([O-])c1ccccc1
Product: COc1ccc(C(=O)c2ccc([N+](=O)[O-])cc2)cc1
Temperature: 0 °C
Reaction time: 8 h
Yield: 55.2 %

Procedure:
150 ml of nitrobenzene were cooled in an ice-bath and treated portionwise with 41 g of aluminium chloride. In so doing, the temperature was held at below 5°. Subsequently, a solution of 50 g of 4-nitrobenzoyl chloride in 50 ml of nitrobenzene was added dropwise in such a manner that the temperature remains at below 5°. At the same temperature there were added dropwise 27.8 g of anisole. Subsequently, the mixture was stirred at 20° overnight. The solution was poured on to 1 liter of ice-water, extracted with methylene chloride, dried over magnesium sulphate and concentrated. The nitrobenzene was distilled off in a high vacuum and the yellowish crystals which remained were recrystallized from cyclohexane. There were obtained 36.5 g (52%) of 4-methoxy-4'-nitrobenzophenone as a yellow solid; m.p. 124°.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]1[C:11](=[O:12])[CH2:10][CH2:9][N:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:7]1)=[O:5])[CH3:2].CCN(C(C)C)C(C)C.[O:29](S(C(F)(F)F)(=O)=O)[S:30]([C:33]([F:36])([F:35])[F:34])(=O)=[O:31].C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH2:7][N:8]([C:13]([O:15][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:14])[CH2:9][CH2:10][C:11]=1[O:12][S:30]([C:33]([F:36])([F:35])[F:34])(=[O:31])=[O:29])=[O:5])[CH3:2]
Reactant: O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
Reactant: CCOC(=O)C1CN(C(=O)OC(C)(C)C)CCC1=O
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CCOC(=O)C1=C(OS(=O)(=O)C(F)(F)F)CCN(C(=O)OC(C)(C)C)C1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 95.7 %

Procedure:
4-Oxo-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester (30.9 g, 114 mmol) was dissolved in CH2Cl2 (800 mL). DIPEA (48.7 mL, 285 mmol) was added, and the reaction mixture was cooled to −78° C. A sol. of Tf2O (24.4 mL, 148 mmol) in CH2Cl2 (25 mL) was added slowly, while maintaining the temperature at −78° C. The mixture was stirred for 30 min at −78° C. The mixture was allowed to warm to rt, and aq. 10% Na2CO3 (400 mL) and ice were added. The layers were separated and the aq. layer was extracted with CH2Cl2 (2×). The combined org. layers were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (heptane→EtOAc/heptane 25:75) yielded the title compound (44.0 g, 91%). LC-MS: tR=1.05 min; ES+: 404.44.
Reaction SMILES: [CH:1]([N:3]([CH2:16][C:17](=O)[CH3:18])[C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[O:14][CH3:15])=O.C([O-])(=O)C.[NH4+:24].C(OCC)(=O)C.C(=O)([O-])O.[Na+]>C(O)(=O)C>[CH3:15][O:14][C:5]1[CH:6]=[C:7]([CH:12]=[CH:13][C:4]=1[N:3]1[CH:16]=[C:17]([CH3:18])[N:24]=[CH:1]1)[C:8]([O:10][CH3:11])=[O:9]
Reactant: COC(=O)c1ccc(N(C=O)CC(C)=O)c(OC)c1
Reactant: [NH4+]
Agent: CC(=O)[O-]
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Product: COC(=O)c1ccc(-n2cnc(C)c2)c(OC)c1
Temperature: 140 °C
Reaction time: 1 h
Yield: 52.9 %

Procedure:
A mixture of methyl 4-[formyl(2-oxopropyl)amino]-3-methoxybenzoate (32.6 g) and ammonium acetate (47.5 g) in acetic acid (65.6 mL) was stirred at 140° C. for 1 hr. After completion of the reaction, ethyl acetate and saturated aqueous sodium hydrogen carbonate solution were added under ice-cooling, and the organic layer was separated. To the aqueous layer was added ethyl acetate, and the organic layer was separated. The organic layers were combined, washed with saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (methanol/ethyl acetate/hexane) to give the title compound (16.0 g).
Reaction SMILES: Cl.[C:2]([C:5]1[CH:13]=[CH:12][C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)([OH:4])=[O:3].[CH2:14](O)[CH3:15]>S(=O)(=O)(O)O>[CH2:14]([O:3][C:2]([C:5]1[CH:13]=[CH:12][C:8]2[N:9]=[CH:10][NH:11][C:7]=2[CH:6]=1)=[O:4])[CH3:15]
Reactant: CCO
Reactant: O=C(O)c1ccc2nc[nH]c2c1
Agent: Cl
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1ccc2nc[nH]c2c1

Procedure:
According to a method similar to that described in Zhur. Obschei Khim., vol. 32, pp 835-41 (1953), 3,4-diaminobenzoic acid was prepared. A formic acid solution (200 ml) of 3,4-diaminobenzoic acid (8 g) thus prepared was refluxed for 4 hrs to yield 5-carboxybenzimidazole.hydrochloride (8.9 g). The carboxylic acid (8.9 g) was refluxed with heating for 3.5 hrs in a mixture of sulfuric acid (4 ml) and absolute ethanol (140 ml) to yield 5-ethoxycarbonylbenzimidazole (mp. 93°-94° C., 7.8 g). An anhydrous tetrahydrofuran solution (20 ml) of the ester (7.5 g) was added to an anhydrous tetrahydrofuran suspension (50 ml) of lithium aluminium hydride (6.5 g) while cooling. The mixture was stirred for 3 hrs at room temperature to yield 5-hydroxymethylbenzimidazole (mp. 128.4° C., 3.62 g). A 47% aqueous hydrobromic acid solution (33 ml) containing the benzimidazole derivative (2.2 g) and cysteamine hydrochloride (1.9 g) was refluxed with heating for 7 hrs to yield 5-[(2-aminoethyl)thiomethyl]benzimidazole.2 hydrobromide (mp. 224°-225° C., 4.2 g).
Reaction SMILES: [NH2:1][C:2]1[S:6][C:5]([CH3:7])=[N:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].F[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21].C(OCC)(=O)C.O.[OH-].[Li+]>CS(C)=O>[CH2:11]([O:10][C:8]([C:3]1[N:4]=[C:5]([CH3:7])[S:6][C:2]=1[NH:1][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1[N+:20]([O-:22])=[O:21])=[O:9])[CH3:12]
Reactant: CCOC(=O)c1nc(C)sc1N
Reactant: O=[N+]([O-])c1ccccc1F
Agent: [Li+]
Agent: [OH-]
Solvent: CS(C)=O
Solvent: O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1nc(C)sc1Nc1ccccc1[N+](=O)[O-]
Reaction time: 1 h

Procedure:
Add a solution of ethyl 5-amino-2-methylthiazole-4-carboxylate (120 g; 645 mmol) and 2-fluoronitrobenzene (68 mL; 645 mmol) in dimethylsulphoxide (1L) to a 2L 3-necked RB flask equipped with reflux condenser, thermometer, mechanical stirrer. Add lithium hydroxide monohydrate (54 g; 1290 mmol) to the solution and heat at 50° C. for 3 hours under nitrogen. Cool the purple solution and pour onto ice/water, allow to stir for one hour, filter and wash with water, dry at 50° C. under reduced pressure to give 190 g (96%) as an orange solid: mass spectrum (m/e): 308(M+1); 1HNMR(300 MHz, DMSO-d6, ppm): δ 1.25(tr, 3H), 2.56(s, 3H), 4.25(q, 2H), 7.20(m, 1H), 7.78(m, 2H), 8.20(d, 1H), 11.42(s, 1H, NH). 13CNMR(75 MHz, DMSO, ppm): δ 24.4, 29.2, 71.2, 127.8, 132.5, 132.8, 137.8, 146.5, 147.0, 147.5, 160.2, 161.5, 173.7. Formula: C13H13N3O4S.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][CH:8]=[CH:7]2)([O-:3])=[O:2].C([O-])([O-])=O.[K+].[K+].Br[CH2:20][C:21]([O:23][CH3:24])=[O:22]>CN(C=O)C>[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:20][C:21]([O:23][CH3:24])=[O:22])[CH:8]=[CH:7]2)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc2[nH]ccc2c1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)Cn1ccc2cc([N+](=O)[O-])ccc21
Yield: 57.4 %

Procedure:
To a solution of 5-nitro-1H-indole (1 g, 6.17 mmol) in DMF (15 ml), K2CO3 (1.023 g, 7.40 mmol) and methyl 2-bromoacetate (0.686 ml, 7.40 mmol) were added, and the mixture was reacted under MW irradiation for 1 hour at 100° C. The insoluble inorganic salts were filtered off, the solvent was removed and the resulting crude was purified by flash chromatography on silica gel column (petroleum ether:ethyl acetate=8:2) to afford methyl 2-(5-nitro-1H-indol-1-yl)acetate (830 mg, 3.54 mmol, 58% yield). MS/ESI+ 234.2[MH]+.
Reaction SMILES: [CH2:1]([N:8]1[CH2:14][CH:13]2[C:15](=O)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C.Cl.[NH2:21][OH:22]>N1C=CC=CC=1>[CH2:1]([N:8]1[CH2:14][CH:13]2[C:15](=[N:21][OH:22])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1C2CCC1CN(Cc1ccccc1)C2
Reactant: NO
Agent: Cl
Solvent: CCO
Solvent: c1ccncc1
Product: ON=C1C2CCC1CN(Cc1ccccc1)C2
Temperature: 100 °C

Procedure:
The mixture of 19 g (88 mmole) of 3-benzyl-3-azabicyclo[3.2.1]octan-8-one (J. Med. Chem. 1994, 37, 2831), 200 ml of ethanol, 8.78 g (126.4 mmole) of hydroxylamine hydrochloride and 13 ml of pyridine are heated and stirred on a 100° C. oil-bath, then the mixture is evaporated. To the residue 65 ml of 2.5 N sodium hydroxide solution is added, the resulting solution is extracted with 3×120 ml of ethyl acetate. The extractum is dried over sodium sulphate and evaporated. The resulting oil is purified by column chromatography (n-hexane-ethyl acetate from 9:1 to 1:1) to obtain 11.05 g (54%) of white, crystalline material. M.p.: 92-95° C. (MH+)=231.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[N:9]=[CH:8][NH:7][N:6]=1)=[O:4].[C:10]1([C:16](Cl)([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3]([C:5]1[N:9]=[CH:8][N:7]([C:16]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]2[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:6]=1)=[O:4]
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: COC(=O)c1nc[nH]n1
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC(=O)c1ncn(C(c2ccccc2)(c2ccccc2)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 96 h
Yield: 28.8 %

Procedure:
A solution of 1H-[1,2,4]triazole-3-carboxylic acid methyl ester (3.0 g, 0.023 mol) in N,N-dimethylformamide at 25° C. was treated with triphenylmethylchloride (7.2 g, 0.025 mol) and triethylamine (6.41 mL, 0.046 mol). The reaction was stirred at 25° C. for 4 days. At this time, the reaction was concentrated in vacuo. The residue was diluted with ethyl acetate and then washed with a dilute 1N aqueous hydrochloric acid solution and a saturated aqueous sodium chloride solution. The organics were dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting solids were diluted with ether, collected by filtration, washed with ether, and dried in vacuo to afford 1-trityl-1H-[1,2,4]triazole-3-carboxylic acid methyl ester (2.45 g, 84%) as a white solid: LR-FAB for C23H19N3O2 (M+H)+ at m/z=370.
Reaction SMILES: [OH-].[K+].[CH2:3](Cl)/[CH:4]=[CH:5]/[CH2:6]Cl.[C:9]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[Cl-]>O>[CH:4]([CH:5]1[CH2:6][C:10]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:9]([O:17][CH2:18][CH3:19])=[O:16])=[CH2:3]
Reactant: CCOC(=O)CC(=O)OCC
Reactant: ClC/C=C/CCl
Agent: [Cl-]
Agent: [K+]
Agent: [OH-]
Solvent: O
Product: C=CC1CC1(C(=O)OCC)C(=O)OCC
Temperature: 25 °C
Reaction time: 5 h
Yield: 20.1 %

Procedure:
Diethyl 2-vinylcyclopropane-1,1-dicarboxylate was prepared as follows: Fifty percent aqueous potassium hydroxide solutin (168 g) was added dropwise to a vigorously stirred solution of 125 g (1.0 mol) trans 1,4-dichlorobutene-2, 80 g (0.50 mol) diethyl malonate and 3.2 g tricaprylymethylammonium chloride while the temperature was maintained at 25°-30° C. When the addition was complete, the reaction mixture was stirred at ambient temperature for an additional five hours. Water was then added to the reaction mixture to completely dissolve the suspended salts in the aqueous phase. The phase layers were separated and the aqueous portion extracted three times with ethyl ether. Distillation of the combined organic solutions gave 21.3 g of the desired diethyl 2-vinylcyclopropane-1,1-dicarboxylate. Bp 64°-66° C. (0.15 mm); nD27° 1.4512; [lit.bp 69°-72° C. (0.5 mm); nD19° 1.4528]. Infrared and proton nmr spectra were consistent with the desired compound. Upon acidification and extraction of the aqueous phase, 19.6 g 2-vinylcyclopropane-1,1-dicarboxylic acid was recovered so that the overall yield of cyclized product was 45.3%.
Reaction SMILES: [C:1]([O:9][CH2:10][CH3:11])(=[O:8])[CH2:2][C:3]([O:5][CH2:6][CH3:7])=[O:4].C1OC1.[OH-].[K+].[CH2:17](Cl)/[CH:18]=[CH:19]/[CH2:20]Cl>C(Cl)Cl>[CH:18]([CH:19]1[CH2:20][C:2]1([C:3]([O:5][CH2:6][CH3:7])=[O:4])[C:1]([O:9][CH2:10][CH3:11])=[O:8])=[CH2:17]
Reactant: ClC/C=C/CCl
Reactant: CCOC(=O)CC(=O)OCC
Agent: [K+]
Agent: [OH-]
Solvent: C1CO1
Solvent: ClCCl
Product: C=CC1CC1(C(=O)OCC)C(=O)OCC

Procedure:
To demonstrate the versatility of the process, 16 g (0.1 mol) diethyl malonate and 62.55 g of a block copolymer of ethylene oxide and polypropylene oxide having an average molecular weight of about 13,300 (Pluronic® 127) were charged to a reactor. Methylene dichloride (100 mls.) and 11.2 g solid potassium hydroxide (90%) were added and the mixture vigorously agitated while maintaining the temperature at or below 35° C. The 1,4-dichlorobutene-2 (12.4 g; 0.1 mol) was then added over a 5 minute period. About 22% conversion to diethyl 2-vinylcyclopropane-1,1-dicarboxylate was obtained after one hour of reaction. The reaction was continued to obtain essentially complete conversion of the reactants to the desired vinylcyclopropane product.
Reaction SMILES: [OH-].[K+].[CH2:3](Cl)/[CH:4]=[CH:5]/[CH2:6]Cl.[C:9]([O:17][CH2:18][CH3:19])(=[O:16])[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12]>CCCCCCCC[N+](CCCCCCCC)(CCCCCCCC)C.[Cl-].O>[CH:4]([CH:5]1[CH2:6][C:10]1([C:11]([O:13][CH2:14][CH3:15])=[O:12])[C:9]([O:17][CH2:18][CH3:19])=[O:16])=[CH2:3]
Reactant: ClC/C=C/CCl
Reactant: CCOC(=O)CC(=O)OCC
Agent: CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC
Agent: [Cl-]
Agent: [K+]
Solvent: O
Product: C=CC1CC1(C(=O)OCC)C(=O)OCC
Temperature: 25 °C
Reaction time: 5 h
Yield: 20.1 %

Procedure:
An aqueous solution (50%) of potassium hydroxide (168 g) was added dropwise to a vigorously stirred solution of 125 g (1.0 mol) trans 1,4-dichlorobutene-2, 80 g (0.5 mol) diethyl malonate and 3.2 g tricaprylmethylammonium chloride while maintaining the temperature at 25°-30° C. When the addition was complete, the mixture was stirred at ambient temperature for five hours and water was then added to dissolve suspended salts. After separation of the phases followed by washing of the aqueous phase three times with ethyl ether, the organic portion was distilled to obtain 21.3 g diethyl 1-vinylcyclopropane-2,2-dicarboxylate. Bp 64°-66° C. (0.15 mm); nD 27° 1.4512; [lit. bp 69°-72° C. (0.5 mm); nD 19° 1.4528]. Infrared and proton nmr spectra were also consistent with the desired compound.