Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.C(NC(C)C)(C)C.[F:13][C:14]1[C:19](I)=[CH:18][CH:17]=[CH:16][N:15]=1.[I:21][CH3:22]>C1COCC1>[F:13][C:14]1[C:19]([CH3:18])=[C:22]([I:21])[CH:17]=[CH:16][N:15]=1
Reactant: Fc1ncccc1I
Reactant: CI
Agent: [Li]CCCC
Solvent: CC(C)NC(C)C
Solvent: C1CCOC1
Product: Cc1c(I)ccnc1F
Reaction time: 1 h
Yield: 88.4 %

Procedure:
n-Butyl lithium (1.6M hexane solution, 53.8 mL) was added to a solution of diisopropylamine (8.71 g) in THF (200 mL) at −10 C. After being stirred at the same temperature under nitrogen atmosphere for 1 hour, a solution of 2-fluoro-3-iodopyridine (18.3 g) in THF (70 mL) was added to the reaction mixture at −78 C. The mixture was stirred at the same temperature under nitrogen atmosphere for 1 hour. A solution of iodomethane (12.8 g) in THF (30 mL) was added to the reaction mixture at −78 C. The mixture was stirred at the same temperature under nitrogen atmosphere for 2 hours. The mixture was quenched with aqueous saturated ammonium chloride solution at 0 C and extracted with ethyl acetate. The organic layer was separated, washed with water and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo. The residue was passed through NH-silica and concentrated in vacuo. The residue was purified by a silica gel column chromatography (hexane/ethyl acetate) to give the title compound (17.2 g).
Reaction SMILES: [OH-].[Na+].[N+:3]([C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[NH:11][N:10]=[CH:9]2)([O-:5])=[O:4].[O-][Cl:16].[Na+].Cl>O>[Cl:16][C:9]1[C:8]2[C:12](=[CH:13][CH:14]=[C:6]([N+:3]([O-:5])=[O:4])[CH:7]=2)[NH:11][N:10]=1
Reactant: O=[N+]([O-])c1ccc2[nH]ncc2c1
Reactant: [O-]Cl
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: O=[N+]([O-])c1ccc2[nH]nc(Cl)c2c1
Temperature: 0 °C
Reaction time: 5 h
Yield: 90.7 %

Procedure:
A mixture of NaOH (5.00 g, 125 mmol) in H2O (150 mL) was added 5-nitroindazole (5.00 g, 30.7 mmol), and the mixture was heated until a red solution formed. The mixture was cooled in an ice-water bath for 15 minutes, NaClO (60.0 mL, 5.25%, 45.0 mmol) was added and the mixture stirred at 0° C. for 5 hour after which the pH was adjusted to 7 with diluted HCl. The mixture was extracted with ethyl acetate, and the combined organic layer washed with H2O and concentrated under reduced pressure. The residue was purified by flash chromatography to provide the title compound (5.5 g, 92%). 1H NMR (300 MHz, DMSO-d6) ppm 7.78 (m, 1H), 8.28 (m, 1H), 8.61 (m, 1H), MS (DCI/NH3) m/Z 197[M+H]+.
Reaction SMILES: [CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11](F)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1.[NH:21]1[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]1.N1C=CC=CC=1.[ClH:33]>O>[ClH:33].[CH:1]1([N:4]2[C:13]3[C:8](=[CH:9][C:10]([F:16])=[C:11]([N:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)[C:12]=3[F:14])[C:7](=[O:17])[C:6]([C:18]([OH:20])=[O:19])=[CH:5]2)[CH2:3][CH2:2]1
Reactant: O=C(O)c1cn(C2CC2)c2c(F)c(F)c(F)cc2c1=O
Reactant: C1CNCCN1
Agent: Cl
Solvent: c1ccncc1
Solvent: O
Product: O=C(O)c1cn(C2CC2)c2c(F)c(N3CCNCC3)c(F)cc2c1=O

Procedure:
A mixture of 2.83 g (0.01 mol) of 1-cyclopropyl-6,7,8-trifluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid (II), 4.4 g (0.051 mol) of anhydrous piperazine and 30 ml of dry pyridine is refluxed for 6 hours. The solvent is stripped off in vacuo, the residue is taken up in 25 ml of water, the pH is adjusted to 1 with concentrated hydrochloric acid, while cooling with ice and, when the mixture is cold, the precipitate is filtered off under suction and washed with cold 10% strength hydrochloric acid and ethanol. After drying in vacuo at 100° C., 3.05 g of 1-cyclopropyl-6,8-difluoro-7-(piperazin-1-yl)-1,4-di- hydro-4-oxoquinoline-3-carboxylic acid hydrochloride having a decomposition temperature of 354°-355° C. are obtained.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10](O)=[O:11])=[CH:4][CH:3]=1.B.O1CCCC1.CO>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:8][CH2:9][CH2:10][OH:11])=[CH:6][CH:7]=1
Reactant: O=C(O)CCc1ccc(Cl)cc1
Agent: B
Solvent: C1CCOC1
Solvent: CO
Product: OCCCc1ccc(Cl)cc1
Temperature: 0 °C
Reaction time: 1 h
Yield: 104 %

Procedure:
To a stirred solution of 3-(4-chlorophenyl)-propionic acid (10.0 g, 54.17 mmol) in tetrahydrofuran (100 ml) at −8° C. was added dropwise borane-tetrahydrofuran complex (100 ml, 1M in tetrahydrofuran, 100 mmol). The reaction mixture was cooled to 0° C. and methanol (100 ml) was added dropwise. The reaction mixture was warmed to room temperature, stirred for one hour and then concentrated in vacuo. The residue was treated with methanol (50 ml) and each time concentrated in vacuo twice to yield the title compound as an oil (9.61 g) which was characterized by IR spectral analysis and used without further purification.
Reaction SMILES: N1C=CN=C1.[Si:6](Cl)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7].[Cl:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][OH:20].[Na+].[Cl-]>CN(C)C=O>[Cl:14][CH2:15][CH2:16][O:17][CH2:18][CH2:19][O:20][Si:6]([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: OCCOCCCl
Agent: [Cl-]
Agent: [Na+]
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)OCCOCCCl
Reaction time: 8 h
Yield: 100.1 %

Procedure:
Imidazole (17.8 g, 261 mmol) was dissolved in dimethylformamide (100 ml) and t-butyldimethylsilyl chloride (36.3 g, 241 mmol) was added and stirred. 2-(2-chloroethoxy)ethanol (25.0 g, 200 mmol) was added dropwise over 1 hour under cooling with ice, and the mixture was stirred for 1 further hour, left standing overnight at room temperature, and then poured into saturated aqueous NaCl (500 ml). The resulting mixture was extracted twice with ether. The extract was washed twice with saturated aqueous NaCl, and dried over MgSO4. Then the solvent was removed in vacuo, giving 1-chloro-2-(2-t-butyldimethylsilyloxyethoxy)ethane (47.8 g, 100% yield). IR (CHCl3) [cm-1 ]; 2920, 2850, 1460, 1100, 930. NMR (CDCl3) [δ ppm]; 3.94-3.90 (4 H, m) 3.79-3.72 (4 H, m), 1.05 (9 H, s), 0.22 (6 H, s).
Reaction SMILES: [CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]=O)=[CH:4][N:3]=1.[ClH:11].[NH2:12][OH:13]>CO>[ClH:11].[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[C:5]([CH:9]=[N:12][OH:13])=[CH:4][N:3]=1
Reactant: NO
Reactant: Cc1ncc(C=O)c(N)n1
Agent: Cl
Solvent: CO
Product: Cc1ncc(C=NO)c(N)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.9 %

Procedure:
To a mixture of 27.4 g of 2-methyl-4-amino-5-formylpyrimidine and 1000 ml of methanol was added, while stirring at room temperature, dropwise gradually 25 ml of an aqueous solution containing 15.2 g of hydroxylamine hydrochloride. The reaction was allowed to proceed for further 3 hours at room temperature, which was then concentrated to dryness under reduced pressure. The concentrate was recrystallized from ethanol to give 25.6 g of 2-methyl-4-amino-5-pyrimidine aldoxime hydrochloride. The resulting mother liquor was concentrated to dryness under reduced pressure, followed by subjecting the concentrate to crystallization from a mixture of methanol/ether (1:1 V/V) to give 10.8 g of 2-methyl-4-amino-5-pyrimidine aldoxime hydrochloride. The total yield was 96.5%.
Reaction SMILES: O.[OH-].[Li+].[C:4]1(/[C:10](=[N:17]/[O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[N:29]=[C:30]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[S:31][CH:32]=3)=[CH:22][CH:21]=2)/[CH2:11][CH2:12][C:13]([O:15]C)=[O:14])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.O.Cl>O1CCCC1>[C:4]1(/[C:10](=[N:17]/[O:18][CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[N:29]=[C:30]([C:33]4[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=4)[S:31][CH:32]=3)=[CH:22][CH:21]=2)/[CH2:11][CH2:12][C:13]([OH:15])=[O:14])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: COC(=O)CC/C(=N\OCc1ccc(OCc2csc(-c3ccccc3)n2)cc1)c1ccccc1
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CC/C(=N\OCc1ccc(OCc2csc(-c3ccccc3)n2)cc1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 89.6 %

Procedure:
Lithium hydroxide monohydrate (54.8 mg) was added to a solution of methyl E-4-phenyl-4-[4-(2-phenyl-4-thiazolylmethoxy)benzyloxyimino]butyrate (424 mg) in tetrahydrofuran (10 ml)-water (4 ml)-metbanol (4 ml) and stirred at room temperature for 2 hours. 1N hydrochloric acid (1.4 ml) was added to the reaction mixture and extracted with ethyl acetate. The ethyl acetate layer was washed with an aqueous saturated solution of sodium chloride, dried (MgSO4) and concentrated. The remaining crystals were recrystallized from ethyl acetate-hexane to obtain E-4-phenyl-4-[4-(2-phenyl-4-thiazolylmethoxy)benzyloxyimino]butyric acid (369 mg, yield 90%) as colorless crystals. m.p. 104-105° C.
Reaction SMILES: CCN(C(C)C)C(C)C.[Br:10][C:11]1[CH:12]=[C:13]([C:27]([O:29][CH3:30])=[O:28])[CH:14]=[C:15]2[C:20]=1[O:19][C:18](S(CC)(=O)=O)=[CH:17][C:16]2=[O:26].Cl.[CH3:32][C@H:33]1[O:38][CH2:37][CH2:36][NH:35][CH2:34]1.Cl>C(Cl)Cl.O>[Br:10][C:11]1[CH:12]=[C:13]([C:27]([O:29][CH3:30])=[O:28])[CH:14]=[C:15]2[C:20]=1[O:19][C:18]([N:35]1[CH2:36][CH2:37][O:38][C@H:33]([CH3:32])[CH2:34]1)=[CH:17][C:16]2=[O:26]
Reactant: C[C@@H]1CNCCO1
Reactant: CCS(=O)(=O)c1cc(=O)c2cc(C(=O)OC)cc(Br)c2o1
Agent: Cl
Solvent: O
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1cc(Br)c2oc(N3CCO[C@H](C)C3)cc(=O)c2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 71.8 %

Procedure:
DIPEA (51.7 mL, 296.91 mmol) was added dropwise to a stirred solution of methyl 8-bromo-2-(ethylsulfonyl)-4-oxo-4H-chromene-6-carboxylate (44.56 g, 118.77 mmol) and (R)-2-methylmorpholine hydrochloride (22.88 g, 166.27 mmol) in DCM (430 mL) at 5° C. under nitrogen. The resulting suspension was stirred at room temperature for 1 h. The reaction mixture was diluted with water and quenched slowly with HCl 1M (119 mL, 118.77 mmol) (pH 7). The phases were separated and the organic phase was washed with water, brine, dried over MgSO4 and concentrated. The crude product was triturated in EtAc for 1 h, the solid was collected by filtration and dried to afford methyl 8-bromo-2-((R)-2-methylmorpholino)-4-oxo-4H-chromene-6-carboxylate (32.6 g, 67%) as a white solid. Mass Spectrum: m/z [M+H]+=384.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1.C(N(CC)CC)C>ClCCl.CS(C)=O>[CH:2]([CH:3]1[CH2:8][CH2:7][N:6]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:5][CH2:4]1)=[O:1]
Reactant: CC(C)(C)OC(=O)N1CCC(CO)CC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: CS(C)=O
Product: CC(C)(C)OC(=O)N1CCC(C=O)CC1
Temperature: 0 °C
Reaction time: 3.5 h
Yield: 60.6 %

Procedure:
To a cooled (0° C.) solution of 4-hydroxymethylpiperidine-1-carboxylic acid, 1,1-dimethylethyl ester (Example 36; 0.82 g, 3.8. mmol) and triethylamine (2.75 mL, 19.76 mmol) in dichloromethane (20 mL) was added sulfur trioxide pyridine complex (2.42 g, 15.2 mmol) in dimethylsulfoxide (10 mL) in three portions and the reaction was stirred at 0° C. for 3.5 h. Examination of the reaction by tlc indicated that some starting alcohol remained, so an additional quantity of sulfur trioxide pyridine complex (1.21 g, 7.6 mmol) in dimethylsulfoxide (5 mL) was added and the reaction was allowed to proceed for another 2 h at 0° C. The reaction mixture was partitioned between saturated sodium bicarbonate solution (60 mL) and diethyl ether/hexane (1:2, 125 mL) and the separated aqueous phase was re-extracted with diethyl ether/hexane (1:2, 2×50 mL). The combined organic extracts were washed with a 1M sodium dihydrogen phosphate solution (50 mL) and with brine (50 mL), then were dried (MgSO4), filtered and evaporated in vacuo. The resulting residual material was chromatographed over silica gel (25% ethyl acetate/petroleum ether) to give 4-formylpiperidine-1-carboxylic acid, 1,1-dimethylethyl ester (0.492 g, 61% yield) as a colorless oil.
Reaction SMILES: [Br:1][CH2:2][C:3](Br)=[O:4].[Cl-].[Cl-].[Ca+2].N1C=CC=CC=1.[CH3:15][O:16][C:17]1[CH:24]=[CH:23][C:20]([CH2:21][OH:22])=[CH:19][CH:18]=1>C1(C)C=CC=CC=1>[Br:1][CH2:2][C:3]([O:22][CH2:21][C:20]1[CH:23]=[CH:24][C:17]([O:16][CH3:15])=[CH:18][CH:19]=1)=[O:4]
Reactant: COc1ccc(CO)cc1
Reactant: O=C(Br)CBr
Agent: [Ca+2]
Agent: [Cl-]
Solvent: c1ccncc1
Solvent: Cc1ccccc1
Product: COc1ccc(COC(=O)CBr)cc1

Procedure:
20.2 g (0.1 mol) of bromoacetyl bromide are dissolved in 100 ml of toluene, this solution is cooled to -10° C. (CaCl2 tube) and 8.7 g (0.11 mol) of pyridine are added dropwise at -10° C. Thereafter, 13.8 g (0.1 mol) of 4-methoxybenzyl alcohol, dissolved in 20 ml of toluene are added dropwise to this mixture in the course of 20 minutes at -10° C., and the mixture is allowed to react for 1 hour at this temperature.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4]Br.[NH:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCCC1>[Cl:1][CH2:2][CH2:3][CH2:4][N:6]1[CH2:11][CH2:10][O:9][CH2:8][CH2:7]1
Reactant: C1COCCN1
Reactant: ClCCCBr
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: C1CCOC1
Product: ClCCCN1CCOCC1
Temperature: 45 °C
Reaction time: 8 h
Yield: 42 %

Procedure:
A solution of 1-chloro-3-bromopropane in dry tetrahydrofuran (2 mL) was added to a cold suspension of morpholine (200 mg, 2.29 mmol) and sodium carbonate (0.63 g, 4.56 mmol) in dry tetrahydrofuran (8 mL). at 0° C. The mixture was stirred at 45° C. overnight. The mixture was allowed to cool to rt, filtered and evaporated to dryness. Purification of the residue by silica gel column chromatography, eluting with a mixture of ethyl acetate and n-heptane (70:30), afforded 3-chloro-1-morpholin-4-yl-propane (156 mg, 42%).
Reaction SMILES: CO[C:3](=[O:5])[O-:4].[CH3:6][N+:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9].C1(=O)[O:19][C:17](=[O:18])[CH:16]=[CH:15]1>O>[C:3]([O-:4])(=[O:5])/[CH:15]=[CH:16]\[C:17]([O-:19])=[O:18].[CH3:6][N+:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9].[CH3:6][N+:7]([CH2:12][CH3:13])([CH2:10][CH3:11])[CH2:8][CH3:9]
Reactant: COC(=O)[O-]
Reactant: O=C1C=CC(=O)O1
Agent: CC[N+](C)(CC)CC
Solvent: O
Product: O=C([O-])/C=C\C(=O)[O-]
Yield: 133 %

Procedure:
By following the same procedure as Example 20 (2nd step) except that 8.8 g of methyltriethylammonium methyl carbonate, 8.8 g of water, and 4.5 g of maleic anhydride were used, 10.6 g (yield of 100%) of methyltriethylammonium maleate was obtained. The content of monomethyl maleate was less than 0.15 and the contents of impurity ions were all less than 1 ppm.
Reaction SMILES: CO[C:3](=[O:5])[O-:4].[CH2:6]([N+:8]([CH3:11])([CH3:10])[CH3:9])[CH3:7].C1(=O)[O:17][C:15](=[O:16])[CH:14]=[CH:13]1>O>[C:3]([O-:4])(=[O:5])/[CH:13]=[CH:14]\[C:15]([O-:17])=[O:16].[CH2:6]([N+:8]([CH3:11])([CH3:10])[CH3:9])[CH3:7].[CH2:6]([N+:8]([CH3:11])([CH3:10])[CH3:9])[CH3:7]
Reactant: O=C1C=CC(=O)O1
Reactant: COC(=O)[O-]
Agent: CC[N+](C)(C)C
Solvent: O
Product: O=C([O-])/C=C\C(=O)[O-]
Yield: 139.8 %

Procedure:
By following the same procedure as Example 20 (2nd step) except that 7.8 g of ethyltrimethylammonium methyl carbonate, 7.8 g of water, and 4.7 g of maleic anhydride were used, 9.7 g (yield of 99.9%) of ethyltrimethylammonium maleate was obtained. The content of monomethyl maleate was less than 0.1% and the contents of impurity ions were all less than 1 ppm.
Reaction SMILES: CO[C:3](=[O:5])[O-:4].[CH3:6][N+:7]1([CH3:12])[CH2:11][CH2:10][CH2:9][CH2:8]1.C1(=O)[O:18][C:16](=[O:17])[CH:15]=[CH:14]1>O>[C:3]([O-:4])(=[O:5])/[CH:14]=[CH:15]\[C:16]([O-:18])=[O:17].[CH3:6][N+:7]1([CH3:12])[CH2:11][CH2:10][CH2:9][CH2:8]1.[CH3:6][N+:7]1([CH3:12])[CH2:11][CH2:10][CH2:9][CH2:8]1
Reactant: COC(=O)[O-]
Reactant: O=C1C=CC(=O)O1
Agent: C[N+]1(C)CCCC1
Solvent: O
Product: O=C([O-])/C=C\C(=O)[O-]
Yield: 136.3 %

Procedure:
By following the same procedure as Example 20 (2nd step) except that 17.5 g of N,N-dimethylpyrrolidinium methyl carbonate, 17.5 g of water, and 9.8 g of maleic anhydride were used, 21.4 g (yield of 99.6%) of N,N-dimethylpyrrolidinium maleate was obtained. The content of mono-maleate was less than 0.1% and the contents of impurity ions were less than 1 ppm.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:9]([O-])=O)=[C:6]([CH3:8])[CH:7]=1.[H][H]>C(OCC)(=O)C.[Pd]>[F:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5](=[CH:4][CH:3]=1)[NH2:9]
Reactant: [H][H]
Reactant: Cc1cc(F)ccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCOC(C)=O
Product: Cc1cc(F)ccc1N

Procedure:
5-Fluoro-2-nitrotoluene (0.5 mole) in ethyl acetate (600 ml.) is hydrogenated at 40 p.s.i. of hydrogen over Pd/C catalyst (1%, 2 teaspoons) at room temperature until the theoretical amount of hydrogen has been taken up. The catalyst is filtered off, and the solvent evaporated to give the crude oil of 4-fluoro-2-toluidine.
Reaction SMILES: [CH3:1][Si:2]([CH3:19])([CH3:18])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[CH:16]=O.[NH2:20][CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1.[BH4-].[Na+]>CO>[CH3:1][Si:2]([CH3:19])([CH3:18])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=2[N:9]=[C:8]1[CH2:16][NH:20][CH:21]1[C:30]2[N:29]=[CH:28][CH:27]=[CH:26][C:25]=2[CH2:24][CH2:23][CH2:22]1
Reactant: C[Si](C)(C)CCOCn1c(C=O)nc2ccccc21
Reactant: NC1CCCc2cccnc21
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: C[Si](C)(C)CCOCn1c(CNC2CCCc3cccnc32)nc2ccccc21
Temperature: 25 °C
Reaction time: 2 h
Yield: 97.7 %

Procedure:
To a stirred solution of 1-(2-trimethylsilylethoxymethyl)-2-formyl-benzimidazole (4.26 g, 15.4 mmol) in dry MeOH (50 mL) was added a solution of 8-amino-5,6,7,8-tetrahydroquinoline (2.20 g, 14.8 mmol) in dry MeOH (20 mL) and the mixture stirred for 2 h at room temperature under an argon atmosphere. The reaction mixture was concentrated under reduced pressure and the resultant residue analyzed by 1H NMR to confirm imine formation. The residue was re-dissolved in dry MeOH (80 mL) and to the resultant solution was added sodium borohydride (1.17 g, 30.8 mmol). The mixture was stirred for 5 h, concentrated in vacuo and diluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (125 mL). The phases were separated and the aqueous layer was extracted with CH2Cl2 (2×75 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo. Purification of the crude material through a plug of silica gel (CH2Cl2/MeOH 96:4) afforded the desired amine (5.91 g, 98%) as an orange oil. 1H NMR (CDCl3) δ −0.07 (s, 9H), 0.90 (t, 2H, J=9 Hz), 1.72-1.83 (m, 2H), 1.95-2.01 (m, 1H), 2.76-2.85 (m, 2H), 3.54 (t, 2H, J=9 Hz), 4.33 (m, 2H), 5.68 (d, 1H, J=12 Hz), 5.75 (d, 1H, J=12 Hz), 7.05-7.09 (m, 1H), 7.25-7.30 (m, 2H), 7.38 (d, 1H, J=9 Hz), 7.44-7.46 (m, 1H), 7.71-7.73 (m, 1H), 8.36-8.38 (m, 1H).
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([C:10]([F:13])([F:12])[F:11])=[CH:6][C:3]=1[CH:4]=O.[C:14]([O:18][CH3:19])(=[O:17])[CH2:15][SH:16].C(=O)([O-])[O-].[K+].[K+].CN(C=O)C>O>[F:11][C:10]([F:13])([F:12])[C:7]1[CH:8]=[CH:9][C:2]2[S:16][C:15]([C:14]([O:18][CH3:19])=[O:17])=[CH:4][C:3]=2[CH:6]=1
Reactant: COC(=O)CS
Reactant: O=Cc1cc(C(F)(F)F)ccc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)c1cc2cc(C(F)(F)F)ccc2s1
Temperature: 60 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
A mixture of 5.0 g of 2-fluoro-5-(trifluoromethyl)benzaldehyde, 3.3 g of methyl thioglycolate, 4.0 g of potassium carbonate and 50 ml of DMF was stirred at 60° C. for 2 hours. The reaction mixture was cooled down to room temperature. To the reaction mixture was added water, and the mixture was extracted with tert-butyl methyl ether three times. The combined organic layers were washed with water and saturated saline, and dried over magnesium sulfate, then, concentrated under reduced pressure. The residue was recrystallized from methanol, to obtain 6.3 g of methyl 5-(trifluoromethyl)benzo[b]thiophene-2-carboxylate (present condensed ring compound 1).
Reaction SMILES: [CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:9][O:10][C:11]1[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=1.C(N(CC)CC)C.[C:25]([O:28][CH2:29][C:30](Cl)=[O:31])(=[O:27])[CH3:26]>C(Cl)Cl>[CH3:9][O:10][C:11]1[CH:17]=[CH:16][C:14]([N:15]2[C@H:1]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C@H:29]([O:28][C:25](=[O:27])[CH3:26])[C:30]2=[O:31])=[CH:13][CH:12]=1
Reactant: CC(=O)OCC(=O)Cl
Reactant: O=Cc1ccccc1
Reactant: COc1ccc(N)cc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: COc1ccc(N2C(=O)[C@@H](OC(C)=O)[C@H]2c2ccccc2)cc1
Temperature: 25 °C
Yield: 68 %

Procedure:
To a solution of 962 mg (4.56 mmol) of the imine derived from benzaldehyde and p-methoxy aniline, and 0.85 mL (6.07 mmol) of triethylamine in 15 mL of CH2Cl2 at -20° C. was added dropwise a solution of 412 mg (3.04 mmol) of α-acetoxy acetyl chloride in 15 mL of CH2Cl2. The reaction mixture was allowed to warm to 25° C. over an 18 h period. The reaction mixture was then diluted with 100 mL of CH2Cl2 and the solution was extracted with 30 mL of 10% aqueous HCl. The organic layer was washed with 30 mL of water and 30 mL of saturated aqueous sodium bicarbonate, dried over sodium sulfate, and concentrated to provide a solid mass. The solid was triturated with 50 mL of hexane and the mixture was filtered. The remaining solid was recrystallized from ethyl acetate/hexane to give 645 mg (68%) of cis-1-p-methoxyphenyl-3-acetoxy-4-phenylazetidin-2-one as white crystals, m.p. 163° C.
Reaction SMILES: CS(C)=O.[O:5]=[CH:6][C@@H:7]([C@H:9]([C@@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8].C(=O)C1OC=CC=1>O>[O:5]=[CH:6][C@H:7]([C@@H:9]([C@@H:11]([CH2:13][OH:14])[OH:12])[OH:10])[OH:8]
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)CO
Solvent: CS(C)=O
Solvent: O=Cc1ccco1
Solvent: O
Product: O=C[C@@H](O)[C@H](O)[C@H](O)CO
Temperature: 160 °C

Procedure:
ICBP Corn Cob (18.9 g, 1-2 mm, 92.5% dry matter) at 25% solid loading was placed in the reactor containing 0.15 M aqueous sulfuric acid (Comparative Example A) or 0.15 M aqueous hydrochloric acid solution (Comparative Example B) (51.1 g) and gradually heated to 160° C. over a period of 13 min and then maintained at this temperature for 30 min as described in the general procedure. At the end of the reaction, the reaction mixture was diluted with water (103.2 g) containing DMSO (1.33 g) and thoroughly mixed. A sample of this reaction mixture was analyzed as described above for xylose and furfural content. The reaction was repeated under identical conditions to validate the reproducibility of data. Results are presented in Table 2. A mixture of furfural, xylose and arabinose was obtained, indicating incomplete conversion of hemicellulose to the desired product furfural.
Reaction SMILES: C(N(CC)CC)C.[Br:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](Cl)=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[N:11][CH:10]=1.[NH2:23][CH2:24][C:25]([CH3:28])([OH:27])[CH3:26]>ClCCl>[Br:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:23][CH2:24][C:25]([CH3:28])([OH:27])[CH3:26])=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[N:16]2)=[N:11][CH:10]=1
Reactant: O=[N+]([O-])c1cnc2cc(Br)cnc2c1Cl
Reactant: CC(C)(O)CN
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(O)CNc1c([N+](=O)[O-])cnc2cc(Br)cnc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 99 %

Procedure:
Triethylamine (35.95 mL, 257.9 mmol) was added to a suspension of 7-bromo-4-chloro-3-nitro[1,5]naphthyridine (49.6 g, 172 mmol) in dichloromethane (500 mL). 1-Amino-2-methylpropan-2-ol (16.86 g, 189 mmol) was added dropwise. The reaction mixture was stirred at ambient temperature for 16 hours and then concentrated under reduced pressure. The residue was triturated with water and stirred for 1 hour. The precipitated solid was isolated by filtration, washed with water, and dried. This material was suspended in diethyl ether (400 mL), sonicated, isolated by filtration, and then dried in a vacuum oven at 40° C. for 16 hours to provide 58.1 g of 1-[(7-bromo-3-nitro[1,5]naphthyridin-4-yl)amino]-2-methylpropan-2-ol as a yellow solid, mp 189-190° C.