Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1.S(Cl)(Cl)=O.[CH3:15]O>>[NH2:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([O:8][CH3:15])=[O:7])=[CH:4][N:3]=1
Reactant: CO
Reactant: Nc1ccc(C(=O)O)cn1
Solvent: O=S(Cl)Cl
Product: COC(=O)c1ccc(N)nc1
Yield: 100 %

Procedure:
6-Aminonicotinic acid (1.06 g, 7.7 mmol) was suspended with stirring in anhydrous methanol (50 ml), and thionyl chloride (0.55 ml, 7.7 mmol) was added dropwise. The suspension was refluxed to a clear solution over 15 hours. The solvent was evaporated in vacuo and the residue taken up in water (20 ml). The solution was raised to pH 9 (sat. Na2CO3), extracted with chloroform, and dried over MgSO4. Evaporation of the chloroform gave 1.23 g (100%) product as white crystals identified by 400 MHz nmr and ir 1694 cm-1.
Reaction SMILES: [CH2:1](C1C2C(=CC=CC=2)NC=1)[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[NH:4][CH:3]=1.C(O[CH2:28][CH3:29])(OCC)OCC.S(=O)(=O)(O)O>CO>[CH:7]1[CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]3[CH:1]=[C:2]4[C:3](=[N:4][C:5]5[C:10]4=[CH:9][CH:8]=[CH:7][CH:6]=5)[CH:29]=[C:28]3[C:6]=12
Reactant: c1ccc2c(Cc3c[nH]c4ccccc34)c[nH]c2c1
Reactant: CCOC(OCC)OCC
Agent: O=S(=O)(O)O
Solvent: CO
Product: c1ccc2c(c1)N=c1cc3c(cc1-2)=Nc1ccccc1-3
Temperature: 25 °C
Yield: 139.7 %

Procedure:
In a 2,000-ml three-necked flask that had been deaerated and filled with nitrogen were placed 50.69 g (205.8 millimoles) of 3,3′-methylenediindole and 30.55 g (206.1 millimoles) of triethyl orthoformate, then 640 g of methanol was added, and the mixture was stirred. To this mixture was added dropwise 5.0 g (51.5 millimoles) of concentrated sulfuric acid over 3 minutes and the mixture was heated under reflux for 1 hour. The mixture was cooled to room temperature and the reddish-brown crystals formed were collected by filtration and washed twice by reslurrying in 500 ml of methanol. The solvent was stripped off under reduced pressure and 36.8 g (143.8 millimoles, 69.9% yield) of indolo[3,2-b]carbazole was obtained as a reddish-brown powder.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.OS(O)(=O)=O.[CH3:17]O>>[Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([O:11][CH3:17])=[O:10])[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)Cc1cccc(Br)c1
Reactant: CO
Agent: O=S(=O)(O)O
Product: COC(=O)Cc1cccc(Br)c1
Temperature: 25 °C
Yield: 69 %

Procedure:
To a solution of 2-(3-bromophenyl) acetic acid (30 g, 0.14 mol) in CH3OH (200 mL) was added a catalytic amount of H2SO4. The mixture was heated at reflux for 6 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated under reduced pressure. The residue was diluted with ethyl acetate (200 mL), which was washed with saturated aqueous Na2CO3, water and brine. The solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give methyl 2-(3-bromophenyl)acetate (22 g, 69%). 1H NMR (CDCl3, 300 MHz) δ 7.44 (s, 1H), 7.42-7.38 (m, 1H), 7.21-7.19 (m, 2H), 3.70 (s, 3H), 3.59 (s, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([CH2:8][C:9]([OH:11])=[O:10])[CH:5]=[CH:6][CH:7]=1.S(Cl)(Cl)=O.[CH3:16]O>>[CH3:16][O:10][C:9](=[O:11])[CH2:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Br:1])[CH:3]=1
Reactant: CO
Reactant: O=C(O)Cc1cccc(Br)c1
Solvent: O=S(Cl)Cl
Product: COC(=O)Cc1cccc(Br)c1
Temperature: 65 °C
Reaction time: 5 h

Procedure:
To 3-bromophenylacetic acid (5.03 g, 23.4 mmol) in MeOH (50 mL) was added thionyl chloride (3.4 mL, 46.8 mmol), and the reaction was stirred at 65° C. for 5 hours. The mixture was concentrated, and the residue was partitioned between CH2Cl2 and saturated aqueous NaHCO3. The mixture was basified with 1N aqueous NaOH, and the aqueous layer was extracted with CH2Cl2. The combined organic layers were washed with H2O, dried over MgSO4, filtered, and concentrated to give the title compound.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][NH:6][N:5]=1)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].Br[CH2:16][CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>CN(C)C=O.CCOC(C)=O>[N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1cc[nH]n1
Reactant: BrCCc1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1ccn(CCc2ccccc2)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 3-nitro-1H-pyrazole (226 mg, 2.0 mmol) in N,N-dimethylformamide (3 mL) were added potassium carbonate (0.33 g, 2.4 mmol) and 1-bromo-2-phenylethane (0.44 g, 2.4 mmol). The resulting mixture was stirred at rt overnight. TLC showed the reaction was complete. The mixture was diluted with EtOAc (40 mL), then washed with water (2×20 mL), brine (20 mL), and dried over anhydrous sodium sulfate. The crude material was purified by chromatography on silica gel, eluting with Hex:EtOAc=80:20→70:30 to give the title compound as a white solid. NOE experiment confirmed the structure. 1H NMR (CDCl3, 400 MHz): δ=3.22 (t, J=7.1 Hz, 2H), 4.43 (t, J=7.1 Hz, 2H), 6.79 (d, J=2.5 Hz, 1H), 7.06-7.09 (m, 2H), 7.12 (d, J=2.5 Hz, 1H), 7.23-7.32 (m, 3H).
Reaction SMILES: [F:1][CH:2]([F:13])[O:3][C:4]1[CH:11]=[CH:10][C:7]([CH:8]=[O:9])=[CH:6][C:5]=1[OH:12].C([O-])([O-])=O.[K+].[K+].CS(C)=O.Br[CH2:25][CH:26]1[CH2:28][CH2:27]1>C1(C)C=CC=CC=1>[CH:26]1([CH2:25][O:12][C:5]2[CH:6]=[C:7]([CH:10]=[CH:11][C:4]=2[O:3][CH:2]([F:13])[F:1])[CH:8]=[O:9])[CH2:28][CH2:27]1
Reactant: O=Cc1ccc(OC(F)F)c(O)c1
Reactant: BrCC1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: Cc1ccccc1
Product: O=Cc1ccc(OC(F)F)c(OCC2CC2)c1
Temperature: 70 °C
Reaction time: 1 h
Yield: 98.9 %

Procedure:
55 g of 4-(difluoromethoxy)-3-hydroxybenzaldehyde, 42.42 g of K2CO3 (1.05 eq), 4.86 g of KI (0.1 eq) and 220 mL of dimethylsulphoxide (DMSO) were loaded in a reactor. The mixture was heated at 70° C. and kept for 1 h. A mixture previously prepared of 42.65 g of bromomethyl cyclopropane (1.08 eq) and 110 mL of DMSO was added for 1 hour. The reaction was kept for 3 h at 70° C., and then cooled at room temperature. Once the temperature was reached, 375 mL of toluene was added. The suspension was filtered to remove the remaining K2CO3, and then it was cooled at 0-5° C., and 375 mL of deionised water were loaded. The phases were separated and the organic phase was washed twice with 55 mL of deionised water. The solvent was removed at reduced pressure, obtaining 70 g (yield 99%) of 3-(cyclopropylmethoxy)-4-(difluoromethoxy)-benzaldehyde as a viscous yellowish fluid.
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]2[C:6]=1[CH2:7][CH2:8][CH2:9][CH2:10]2)(=[O:3])[CH3:2].S([O-])([O-])(=O)=[O:17].[Mg+2].[Mn]([O-])(=O)(=O)=O.[K+].C([C@]1(O)C2C=C3N(CC4C3=NC3C=CC(F)=C5C(N6C(=O)C7C(=CC=CC=7)C6=O)CCC=4C=35)C(=O)C=2COC1=O)C>CC(C)=O.O>[C:1]([NH:4][C:5]1[CH:14]=[C:13]([F:15])[CH:12]=[C:11]2[C:6]=1[C:7](=[O:17])[CH2:8][CH2:9][CH2:10]2)(=[O:3])[CH3:2]
Reactant: O=S(=O)([O-])[O-]
Reactant: CC(=O)Nc1cc(F)cc2c1CCCC2
Agent: O=[Mn](=O)(=O)[O-]
Agent: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccc(F)c3c1c2CCC3N1C(=O)c2ccccc2C1=O
Agent: [K+]
Solvent: O
Solvent: CC(C)=O
Product: CC(=O)Nc1cc(F)cc2c1C(=O)CCC2
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To a solution of the compound obtained in (6) above (9.46 gm) in 420 ml of acetone was added 42 ml of 15% aqueous solution of magnesium sulfate. After cooling to 0° C., 21.7 gm of potassium permanganate was added to the mixture, a bit at a time. The mixture was stirred for 50 minutes at 0° C. and for 1 hour at room temperature. Upon addition of 11 of water, the reaction product was extracted 3 times with chloroform. The chloroform layer was washed with water and saturated brine in this order, and dried over anhydrous sodium sulfate. The solvent was evaporated and the residue was subjected to silica gel column chromatography using hexane-ethyl acetate (3:1) as an eluant to obtain fractions containing the target compound. The fractions were concentrated to obtain 7.98 gm of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH3:10][C:11]([CH2:15]O)([CH2:13][OH:14])[CH3:12]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[O:14][CH2:13][C:11]([CH3:15])([CH3:12])[CH2:10][O:7]2)=[CH:4][CH:3]=1
Reactant: O=Cc1ccc(Br)cc1
Reactant: CC(C)(CO)CO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: CC1(C)COC(c2ccc(Br)cc2)OC1
Temperature: 25 °C
Yield: 64 %

Procedure:
The following describes an improved procedure at three times larger scale in much shorter time compared with the literature (Hewlins et al. (1986) J. Chem. Res. (M), 8: 2645–2696). 4-Bromobenzaldehyde (3.00 g, 16.2 mmol), neopentylglycol (1.86 g, 17.9 mmol) and p-toluenesulfonic acid (50 mg, 0.3 mmol) were dissolved in toluene (30 mL) and the solution was refluxed for 3 h. Then the solution was cooled to rt, washed twice with aq NaHCO3 (10%), twice with water and dried (Na2SO4). The solvent was evaporated and the oily residue was crystallized from hexanes, affording colorless needles (2.81 g, 64%). 13C NMR (APT) δ 21.7 (−), 22.9 (−), 30.1 (+), 77.5 (+), 100.8 (−), 122.7 (+), 127.8 (−), 131.3 (−), 137.5 ((+)).
Reaction SMILES: C([N:8]1[C:16]2[CH:15]=[CH:14][N:13]=[C:12]([O:17][CH3:18])[C:11]=2[CH:10]=[C:9]1[CH3:19])C1C=CC=CC=1.CC(C)([O-])C.[K+]>C1COCC1>[CH3:18][O:17][C:12]1[C:11]2[CH:10]=[C:9]([CH3:19])[NH:8][C:16]=2[CH:15]=[CH:14][N:13]=1
Reactant: COc1nccc2c1cc(C)n2Cc1ccccc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COc1nccc2[nH]c(C)cc12
Temperature: 0 °C

Procedure:
To a solution of 1-benzyl-4-methoxy-2-methyl-1H-pyrrolo[3,2-c]pyridine (2) (0.887 g, 3.51 mmole) in anhydrous THF (10 mL) dimethyl sulfoxide (25 mL) was added slowly (via a syringe) and the mixture was cooled to 0° C. Potassium tert-butoxide (1M in THF, 25 mL, 25 mmole) was added slowly. Oxygen was bubbled through the mixture for 45 minutes. The reaction was quenched with saturated ammonium chloride solution, the mixture was extracted with ethyl acetate (3×50 mL). The organic layer was separated, dried over magnesium sulphate and concentrated. The residue was purified by column chromatography (3:1 Hex:EtOAc) to afford intermediate (3). Yield: 1.06 g >100%
Reaction SMILES: C(N[C:5]1[C:6]([N+:16]([O-:18])=[O:17])=[C:7]([C:11]([Cl:15])=[CH:12][C:13]=1[Cl:14])[C:8]([OH:10])=[O:9])(=O)C.[OH-:19].[K+].Cl>O.C(OCC)(=O)C>[Cl:14][C:13]1[CH:12]=[C:11]([Cl:15])[C:7]([C:8]([OH:10])=[O:9])=[C:6]([N+:16]([O-:18])=[O:17])[C:5]=1[OH:19]
Reactant: [OH-]
Reactant: CC(=O)Nc1c(Cl)cc(Cl)c(C(=O)O)c1[N+](=O)[O-]
Agent: Cl
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: O=C(O)c1c(Cl)cc(Cl)c(O)c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 89 %

Procedure:
3-Acetamido-4,6-dichloro-2-nitrobenzoic acid (1-5) (9.7 g, 0.033 mol) was added to a solution of KOH (18.7 g, 0.034 mol) in H2O (85 mL). The solution was heated under reflux for 18 h and cool to room temperature. Conc HCl was added to adjust the pH to 0. The mixture was diluted with ethyl acetate and H2O and left to stir at room temperature for 30 min. The layers were separated; the aqueous layer was extracted with ethyl acetate (3×), the extracts combined with the original organic layer, washed with brine, dried and concentrated to yield 4,6-dichloro-3-hydroxy-2-nitrobenzoic acid (1-6) as a dark red solid (7.4 g, 89%); m.p. 188-189° C. (lit.4 m.p. 186° C. (dec)).
Reaction SMILES: [NH2:1][C:2]1[C:3]([Cl:9])=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.N1C=CC=CC=1.[C:16]1([S:22](Cl)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C(Cl)Cl>[Br:8][C:6]1[CH:7]=[C:2]([NH:1][S:22]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:24])=[O:23])[C:3]([Cl:9])=[N:4][CH:5]=1
Reactant: O=S(=O)(Cl)c1ccccc1
Reactant: Nc1cc(Br)cnc1Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=S(=O)(Nc1cc(Br)cnc1Cl)c1ccccc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 34.6 %

Procedure:
To a stirred solution of 3-amino-5-bromo-2-chloropyridine (5.0 g, 24 mMol) in CH2Cl2 (50 mL) was added pyridine (3.0 mL, 37 mMol) followed by benzenesulfonyl chloride (4.5 mL, 35 mMol) drop wise over 5 minutes. The reaction was stirred at RT for 18 h and evaporated to dryness under vacuum. Purified by flash chromatography on silica gel (15% hexanes in CH2Cl2 then 0 to 5% EtOAc in 15% hexanes in CH2Cl2). During evaporation of the solvents the product crashed out. The resultant slurry was diluted with hexane, filtered and dried under vacuum to give the title compound (2.89 g, 34%) as a white solid. [An overlap fraction which contained 30% starting amine (2.60 g) was also obtained.]: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.61 (br. s., 1H), 8.41 (d, J=2.27 Hz, 1H), 7.91 (d, J=2.27 Hz, 1H), 7.73-7.77 (m, 2H), 7.67-7.72 (m, 1H), 7.56-7.64 (m, 2H); MS (ES) m/e 346.7 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:9]([CH:10]=1)=[C:8]([C:11]([F:14])([F:13])[F:12])[C:7]([C:15]#[N:16])=[CH:6][CH:5]=2.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26]>CN(C=O)C>[C:15]([C:7]1[C:8]([C:11]([F:12])([F:14])[F:13])=[C:9]2[C:4](=[CH:5][CH:6]=1)[N:3]([CH:24]([CH3:29])[C:25]([O:27][CH3:28])=[O:26])[C:2]([CH3:1])=[CH:10]2)#[N:16]
Reactant: Cc1cc2c(C(F)(F)F)c(C#N)ccc2[nH]1
Reactant: COC(=O)C(C)Br
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Product: COC(=O)C(C)n1c(C)cc2c(C(F)(F)F)c(C#N)ccc21
Temperature: 90 °C
Yield: 100.9 %

Procedure:
A mixture of 2-methyl-4-(trifluoromethyl)-1H-indole-5-carbonitrile (see, for example, US2008139631A1) (0.300 g, 1.338 mmol), cesium carbonate (0.654 g, 2.007 mmol) and methyl 2-bromopropanoate (0.223 mL, 2.007 mmol) in DMF (3 mL) was heated at 90° C. for 1 h. Upon cooling, the reaction mixture was partitioned between Et2O (30 mL) and water (25 mL). The organic phase was washed with water (20 mL) and brine (10 mL). The combined aqueous phases were washed with Et2O (2×25 ml). The organic phases were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The residue was chromatographed over silica gel eluting with 5-40% EtOAc-hexane gradient to give methyl 2-[5-cyano-2-methyl-4-(trifluoromethyl)-1H-indol-1-yl]propanoate (0.419 g, 94% yield): MS (ESI): m/z 311 (MH+).
Reaction SMILES: [NH2:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:4][CH:3]=1.[Cl:13]N1C(=O)CCC1=O.CCCCCC.CCOC(C)=O>C(#N)C>[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])=[CH:11][C:12]=1[Cl:13]
Reactant: O=C1CCC(=O)N1Cl
Reactant: CCOC(=O)c1ccc(N)cc1
Solvent: CC#N
Solvent: CCOC(C)=O
Solvent: CCCCCC
Product: CCOC(=O)c1ccc(N)c(Cl)c1

Procedure:
Ethyl p-aminobenzoate, 49.50 g (0.30 moles) was dissolved in 500 ml of acetonitrile (CH3CH) and heated to ref lux. When the mixture became homogeneous, 42.0 g (0.315 moles) of N-chlorosuccinimide was added in several portions over one hour and the mixture was stirred at reflux overnight. By TLC (Hexane: EtOAc, 3:1), the mixture contained no starting material but only the desired product (Rf=0.55) and a minor impurity, which was probably dichlorinated material (Rf=0.65). The mixture was concentrated on a rotary evaporator and the residue was redissolved in 250 mL of dichloromethane (CH2Cl2) and washed twice with 100 mL of 5% sodium hydroxide (NaOH). The organic layer was dried over anhydrous potassium carbonate (K2CO3) and concentrated on a rotary evaporator to yield 62.0 g of a reddish brown solid. The solid was recrystallized from 1.25 L of boiling hexane to give 52 g of a brown solid. The solid was recrystallized twice more from 1 L of boiling hexane to give 45.5 g (76%) of tan solid ethyl 4-amino-3-chlorobenzoate (2), mp 82-83° C. and homogeneous by TLC. Additional material, 9.6 g (16%) of like quality, was obtained by repeated recrystallization from hexane. The total yield of pure ethyl 4-amino-3-chlorobenzoate (2) was 92%. 1H NMR (CDCl3) d 7.97-7.96 (t, 1H, J=0.7 Hz, ArH), 7.80-7.75 (dt, 1H, J=0.7 Hz, ArH), 6.77-6.73 (dd, 1H, J=0.5 Hz, ArH), 4.40-4.29 (q, 2H, J=2.8 Hz, OCH2), 1.41-1.34 (t, J=2.8 Hz, 2H, OCH2CH3). IR (KBr) cm−1, 3500, 3370 (NH2, m), 1695, (C═O, s) 1630. MS (El) m/e 199 (M+), 201 (M+2), Anal. Calc'd for C9H10NO2. Cl: C, 54.15; H, 5.05: N, 7.02. Fd. C, 54.14; H, 5.17, N, 6.93.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[CH:13]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=3)[S:12][C:11](=[S:22])[N:10]=2)=[CH:5][CH:4]=1.[CH3:23][O:24][CH:25]([O:28][CH3:29])[CH2:26]Br.[H-].[Na+].C(OCC)C>CN(C)P(=O)(N(C)C)N(C)C>[CH3:23][O:24][CH:25]([O:28][CH3:29])[CH2:26][S:22][C:11]1[S:12][C:13]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[CH:16][CH:15]=2)=[C:9]([C:6]2[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=2)[N:10]=1
Reactant: COc1ccc(C2=NC(=S)SC2c2ccc(OC)cc2)cc1
Reactant: COC(CBr)OC
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)P(=O)(N(C)C)N(C)C
Solvent: CCOCC
Product: COc1ccc(-c2nc(SCC(OC)OC)sc2-c2ccc(OC)cc2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
20.0 g of 4,5-bis-(p-methoxyphenyl)-thiazoline-2-thione are dissolved in 100 ml of hexamethylphosphoric acid triamide at 35°. The mixture is allowed to cool to 20°, first 11.2 g of 2-bromoacetaldehyde-dimethylacetal and then, in portions, 2.9 g of 50% strength sodium hydride suspension (in mineral oil, de-oiled with hexane) are added, the reaction temperature being maintained at 25°-30° by cooling. The mixture is then stirred at room temperature for 1 hour, poured onto ice, the oil which separates is brought into solution with diethyl ether, and the organic phase is removed. The aqueous phase is extracted by shaking again with 200 ml of diethyl ether. The organic phases are combined, washed with 200 ml of 2 N sodium hydroxide solution, dried over magnesium sulphate and concentrated by evaporation. The oily crude product is crystallised from hexane and made into a slurry with methanol. 2-[4,5-bis-(p-methoxyphenyl)-thiazol-2-ylthio]-acetaldehyde-dimethylacetal having a melting point of 60°-61° is obtained.
Reaction SMILES: [N+:1]([CH:4]([CH3:6])[CH3:5])([O-:3])=[O:2].[C:7]([O:11][CH3:12])(=[O:10])[CH:8]=[CH2:9].Cl.O>O1CCOCC1.[OH-].C([N+](C)(C)C)C1C=CC=CC=1.C(OCC)C>[CH3:5][C:4]([N+:1]([O-:3])=[O:2])([CH3:6])[CH2:9][CH2:8][C:7]([O:11][CH3:12])=[O:10]
Reactant: CC(C)[N+](=O)[O-]
Reactant: C=CC(=O)OC
Agent: C[N+](C)(C)Cc1ccccc1
Agent: Cl
Agent: [OH-]
Solvent: C1COCCO1
Solvent: O
Solvent: CCOCC
Product: COC(=O)CCC(C)(C)[N+](=O)[O-]
Temperature: 70 °C
Yield: 71.1 %

Procedure:
According to the method of R. B. Moffett, Organic Syntheses, Coll. Vol. 4, p. 652 (1963), a 250-mL three-necked flask was fitted with a dropping funnel, and a thermometer placed so that the bulb was near the bottom of the flask. A solution of 2-nitropropane (45.5 mL, 0.5 mol) in dioxane (25 mL) and a 40% aqueous solution of benzyltrimethylammonium hydroxide (Triton B, 5 mL, 0.013 mmol) were added to the flask. The flask was heated to 70° C. in an oil bath and methyl acrylate (45 mL, 0.5 mol) was added via a dropping funnel over 15 minutes. The temperature rose to about 100° C. during the addition then dropped to ˜85° C. The mixture was then heated at 100° C. for 4 h. The reaction mixture was cooled to room temperature and acidified with 1 N hydrochloric acid (10 mL). Water (200 mL) and diethyl ether (400 mL) were added to the reaction flask. The mixture was poured into a separatory funnel and organic layer was washed with water (2×200 mL), brine (200 mL), dried over anhydrous MgSO4, filtered and concentrated under reduced pressure to give a yellow liquid. The product was distilled through a short path distillation apparatus to give a pale yellow liquid (62.3 g, 71.1%). 1H NMR (CDCl3, 400 MHz): δ 1.60 (s, 6H), 2.22-2.38 (m, 4H), 3.70 (s, 3H).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1.[CH3:11][N:12]([CH3:18])[CH2:13][CH2:14][CH2:15][NH:16][CH3:17]>>[CH3:11][N:12]([CH3:18])[CH2:13][CH2:14][CH2:15][N:16]([CH3:17])[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][CH:3]=1
Reactant: CNCCCN(C)C
Reactant: O=[N+]([O-])c1ccc(F)cc1
Product: CN(C)CCCN(C)c1ccc([N+](=O)[O-])cc1

Procedure:
Prepared from 1-fluoro-4-nitrobenzene and 1-dimethylamino-3-methylamino-propane
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][N:10]=1)[C:5]([OH:7])=[O:6].[CH2:11](O)[CH3:12].OS(O)(=O)=O>C(OCC)(=O)C>[CH2:11]([O:6][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][N:10]=[C:2]([Cl:1])[CH:3]=1)[CH3:12]
Reactant: O=C(O)c1ccnc(Cl)c1
Reactant: CCO
Agent: O=S(=O)(O)O
Solvent: CCOC(C)=O
Product: CCOC(=O)c1ccnc(Cl)c1
Temperature: 25 °C

Procedure:
The mixture of 2-chloro-isonicotinic acid (16.8 g, 0.107 mol), 100 mL absolute ethanol and concentrate H2SO4 (3.28 mL, 0.118 mol) was refluxed under nitrogen for 15 h. After all starting material converted, the mixture was cool down to rt, and vacuumed down all ethanol. The resulted mixture was diluted with 250 mL ethyl acetate, washed with sat. NaHCO3, dried over anhydrous Na2SO4. Purified by a short column, the 2-chloro-isonicotinic acid ethyl ester was obtained in as a pale yellow liquid. MS (ES+): 186 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[CH3:12]O>S(=O)(=O)(O)O>[CH3:12][O:6][C:5](=[O:7])[C:4]1[CH:8]=[CH:9][CH:10]=[C:2]([Cl:1])[C:3]=1[CH3:11]
Reactant: CO
Reactant: Cc1c(Cl)cccc1C(=O)O
Agent: O=S(=O)(O)O
Product: COC(=O)c1cccc(Cl)c1C
Temperature: 25 °C

Procedure:
Approximately two drops of sulfuric acid were added to a solution of 3-chloro-2-methyl-benzoic acid (5.00 g, 29.30 mmol) in methanol and the resulting reaction mixture was refluxed for 14 hours. The reaction mixture was cooled to room temperature, and concentrated, then diluted with EtOAc. The organic layer was washed with saturated NaHCO3 (3×150 mL), H2O (2×250 mL), brine (1×250 mL) and dried over MgSO4. The crude product was purified by column chromatography using hex:EtOAc (4.5:0.5) as the eluant to give the title ester. Spectroscopic data: 1H NMR (300 MHz, CDCl3.) δ 2.60 (s, 3H), 3.90 (s, 3H), 7.16 (t, J=7.325 Hz, 1H), 7.49 (d, J=7.91 Hz, 1H), 7.69 (d, J=7.91 Hz, 1H).
Reaction SMILES: [CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11].Cl.[NH2:14][OH:15].C([O-])(=O)C.[Na+]>O1CCCC1.O>[CH3:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[N:14][OH:15])=[CH:4][C:3]=1[N+:10]([O-:12])=[O:11]
Reactant: Cc1ccc(C=O)cc1[N+](=O)[O-]
Reactant: NO
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(C=NO)cc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h
Yield: 91.7 %

Procedure:
A solution of 4-methyl-3-nitrobenzaldehyde (3.5 g) in tetrahydrofuran (50 mL) was added dropwise to a solution of hydroxylamine hydrochloride (3.0 g) and sodium acetate (4.0 g) in tetrahydrofuran (50 mL) and water (50 mL) under ice cooling, and, on completion of the dropwise addition, the mixture was stirred for one hour at room temperature. The reaction solution was diluted with water and then extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain a crude product of 4-methyl-3-nitrobenzaldehyde oxime (3.5 g).