Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH2:11][C:12]#[N:13].[H-].[Na+].Br[CH2:17][CH2:18][O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1>C1COCC1.ClCCl>[CH:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][C:2]=1[CH:11]([CH2:17][CH2:18][O:19][CH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][O:21]1)[C:12]#[N:13]
Reactant: BrCCOC1CCCCO1
Reactant: N#CCc1ccc2ccccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: ClCCl
Product: N#CC(CCOC1CCCCO1)c1ccc2ccccc2c1
Temperature: 20 °C
Reaction time: 2 h
Yield: 33.5 %

Procedure:
2-Napthylacetonitrile (3.3442 g, 20 mmol) in THF (50 mL) was added to sodium hydride (0.528 g, 22 mmol, 1.1 eq.) in THF (50 mL) at -78° C. under nitrogen. The slurry was allowed to warm to 20° C. and stir for 2 hours. The slurry was cooled to 0° C. and 2-(2-bromo-ethoxy)-tetrahydro-pyran (4.1786 g, 20 mmol, 1 eq.) was added. The solution was allowed to stir at 20° C. for 16 hours and then diluted with dichloromethane and washed with water. The organic phase was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was chromatographed on silica gel with a gradient from 5% ethyl acetate in hexane to ethyl acetate to give 1.9774 g (66%) of the title compound. 12.2 Synthesis of 3-cyano-3-naphthalen-2-yl-5-(tetrahydro-pyran-2-yloxy)-pentanoic acid ethyl ester (003F143).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6]([CH:7]=O)=[CH:5][CH:4]=1.[C:11]1(=[O:21])[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][CH2:13][CH2:12]1.[OH-].[K+]>O1CCCC1>[CH3:1][O:2][C:3]1[CH:10]=[CH:9][C:6](/[CH:7]=[C:12]2/[C:11](=[O:21])[C:20]3[C:15]([CH2:14][CH2:13]/2)=[CH:16][CH:17]=[CH:18][CH:19]=3)=[CH:5][CH:4]=1
Reactant: COc1ccc(C=O)cc1
Reactant: O=C1CCCc2ccccc21
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Product: COc1ccc(/C=C2\CCc3ccccc3C2=O)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 60 %

Procedure:
A mixture of p-methoxybenzaldehyde (10.00 g, 73.4 mmol, 1.3 eq) and 1-tetralone (8.24 g, 56.4 mmol, 1 eq) was dissolved in tetrahydrofurane (30 mL) and a methanolic solution of potassium hydroxide (4% solution, 250 mL, 7.9 g KOH, 141 mmol, 2.5 eq) was added dropwise over a 15 minutes period to the stirred solution. The mixture was stirred at ambient temperature for three days and the formed precipitate was separated by filtration and purified by washing with MTBE. After drying in vacuo a pale yellow solid (8.57 g, 60% yield, GC-MS purity 99%) was obtained. The filtrate was reduced to a quarter of its volume and a second fraction (3.7 g, 26% yield, GC-MS purity 100%) could be isolated after filtration and washing with a low amount of methanol and a higher amount of MTBE. The over-all yield was 86% and the product was directly used in the next step without any further purification.
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:12])([CH3:11])[O:6][CH:7]1[CH2:10][NH:9][CH2:8]1)([CH3:4])[CH3:3].C(N(CC)C(C)C)(C)C.[CH3:22][C:23]([O:26][C:27]([N:29]1C(C2C=CC(C#N)=CC=2)O1)=[O:28])([CH3:25])[CH3:24]>ClCCl>[C:23]([O:26][C:27](=[O:28])[NH:29][N:9]1[CH2:10][CH:7]([O:6][Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:12])[CH3:11])[CH2:8]1)([CH3:25])([CH3:24])[CH3:22]
Reactant: CC(C)(C)[Si](C)(C)OC1CNC1
Reactant: CC(C)(C)OC(=O)N1OC1c1ccc(C#N)cc1
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)NN1CC(O[Si](C)(C)C(C)(C)C)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 73.5 %

Procedure:
3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-azetidine (300 mg, 1.6 mmol) was combined with dichloromethane (16 mL) to give a brown solution. N,N-Diisopropylethylamine (455 mg, 615 μl, 3.52 mmol) was added at 0° C. Subsequently 3-(4-cyanophenyl)-2-oxaziridinecarboxylic acid 1,1-dimethylethyl ester (355 mg, 1.44 mmol) in dichloromethane (10 mL) was added during 25 min at 0° C. and the reaction mixture was stirred for 1 h at 0° C. Afterwards the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 20 g, 0% to 40% ethyl acetate in n-heptane) to deliver an oil contaminated with 4-cyano-benzaldehyde. This material was purified by a second chromatography (aminophase 12 g, ethyl acetate/n-heptane 1/1) to give the title compound (320 mg, 67%) as white waxy solid; GC-MS (EI) 302.0 (M)+.
Reaction SMILES: [Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:4](Cl)[N:3]=1.[CH3:17][O:18][C:19]1[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[CH:23][C:20]=1[CH2:21][NH2:22]>C(N(CC)CC)C>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[CH:11]2[CH2:15][CH2:14][CH2:13][CH2:12]2)=[C:4]([NH:22][CH2:21][C:20]2[CH:23]=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:19]=2[O:18][CH3:17])[N:3]=1
Reactant: Clc1nc(Cl)c2ncn(C3CCCC3)c2n1
Reactant: COc1ccc(CN)c(OC)c1
Solvent: CCN(CC)CC
Product: COc1ccc(CNc2nc(Cl)nc3c2ncn3C2CCCC2)c(OC)c1

Procedure:
2-Chloro-6-[(2,4-dimethoxybenzyl)amino]-9-cyclopentylpurine is prepared from 2,6-dichloro-9-cyclopentylpurine, 2,4-dimethoxybenzylamine, and triethylamine essentially as described above in Example 1, Scheme A, step b.
Reaction SMILES: P(Br)(Br)[Br:2].[S:5]1[C:9]([CH2:10]O)=[CH:8][C:7]2[CH:12]=[CH:13][C:14]3[C:19]([C:6]1=2)=[CH:18][CH:17]=[CH:16][CH:15]=3>C(Cl)(Cl)Cl>[Br:2][CH2:10][C:9]1[S:5][C:6]2[C:19]3[C:14]([CH:13]=[CH:12][C:7]=2[CH:8]=1)=[CH:15][CH:16]=[CH:17][CH:18]=3
Reactant: BrP(Br)Br
Reactant: OCc1cc2ccc3ccccc3c2s1
Solvent: ClC(Cl)Cl
Product: BrCc1cc2ccc3ccccc3c2s1
Temperature: 0 °C
Reaction time: 5 h

Procedure:
A solution of 10.8 g (0.04 mole) of phosphorus tribromide in 150 ml of chloroform is added dropwise at 5° within 45 minutes, with stirring, to a suspension of 21.4 g (0.1 mole) of naphtho [1,2-b]thiophene-2-methanol in 110 ml of chloroform, with the gradual formation of a solution. The reaction mixture is stirred for a further 5 hours at 5°, and ice water is subsequently added. The organic phase is separated, washed twice with water and, after drying over sodium sulphate, concentrated at a maximum of 40° in vacuo. The 2-(bromomethyl)-naphtho[1,2-b] thiophene obtained as residue crystallises on addition of diethyl ether, and melts at 75°-78°.
Reaction SMILES: Cl.[C:2]1(=[O:13])[C:7]2([CH2:12][CH2:11][NH:10][CH2:9][CH2:8]2)[CH2:6][CH2:5][CH2:4][NH:3]1.C([O-])([O-])=O.[K+].[K+].Cl[C:21]1[CH:30]=[N:29][C:28]2[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=2)[N:22]=1>CN(C=O)C>[N:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[N:29]=[CH:30][C:21]=1[N:10]1[CH2:11][CH2:12][C:7]2([C:2](=[O:13])[NH:3][CH2:4][CH2:5][CH2:6]2)[CH2:8][CH2:9]1
Reactant: O=C1NCCCC12CCNCC2
Reactant: Clc1cnc2ccccc2n1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1NCCCC12CCN(c1cnc3ccccc3n1)CC2
Temperature: 60 °C
Yield: 78.3 %

Procedure:
To the stirred solution of 2,9-diazaspiro[5.5]undecan-1-one hydrochloride (2.2 g, 10.78 mmol) in DMF (15 mL) was added K2CO3 (4.45 g, 32.24 mmol) and 2-chloro quinoxaline (1.94 g, 11.82 mmol). The mixture was heated at 60° C. for 18 h. The reaction mixture was cooled to rt and concentrated under reduced pressure. To the crude mixture water was added and extracted with ethyl acetate. The organic layer was dried over anhydride sodium sulfate, filtered and concentrated to obtain a yellow solid which was triturated with n-pentane to yield a yellow solid (2.5 g, 78%). [1H-NMR (DMSO-d6, 300 MHz): δ 8.91 (s, 1H), 7.81 (d, 1H), 7.62-7.55 (m, 2H), 7.42-7.33 (m, 2H), 4.33-4.19 (m, 2H), 3.52-3.33 (m, 2H), 3.20-3.05 (m, 2H), 2.12-1.98 (m, 2H), 1.95-1.64 (m, 4H), 1.59-1.48 (m, 2H); HPLC RtA=3.665 min (97%); LCMS RtA=0.377, [M+H]+=297.1].
Reaction SMILES: C([N:8](CC1C=CC=CC=1)[C@@H:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[C:13]2[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:12]=2[O:11][C@@H:10]1[CH2:27][CH3:28])C1C=CC=CC=1>CO.[Pd]>[NH2:8][C@@H:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([F:19])([F:21])[F:20])[C:13]2[CH:22]=[C:23]([F:26])[CH:24]=[CH:25][C:12]=2[O:11][C@@H:10]1[CH2:27][CH3:28]
Reactant: CC[C@H]1Oc2ccc(F)cc2N(CC(F)(F)F)C(=O)[C@H]1N(Cc1ccccc1)Cc1ccccc1
Agent: [Pd]
Solvent: CO
Product: CC[C@H]1Oc2ccc(F)cc2N(CC(F)(F)F)C(=O)[C@H]1N
Yield: 66 %

Procedure:
The title compound was prepared in 66% yield by hydrogenation of (6R,7S)-7-dibenzylamino-6-ethyl-2-fluoro-9-(2,2,2-trifluoro-ethyl)-6,7-dihydro-9H-5-oxa-9-aza-benzocyclohepten-8-one in methanol with Pd/C (10%), MS m/e (%): 307.1 (M+H+, 100).
Reaction SMILES: [CH3:1][Si:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(Cl)[Cl:3].[OH2:11]>CCOCC>[CH3:1][Si:2]([Cl:3])([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)[O:11][Si:2]([Cl:3])([CH3:1])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: C[Si](Cl)(Cl)c1ccccc1
Reactant: O
Solvent: CCOCC
Product: C[Si](Cl)(O[Si](C)(Cl)c1ccccc1)c1ccccc1
Yield: 33.5 %

Procedure:
Methylphenyl dichlorosilane (765 g; 4.0 mol.) and the same amount of diethyl ether were introduced into a four-necked flask of 2 liters volume equipped with a stirring machine, a reflux condenser, a thermometer and a dropping funnel, followed by stirring the mixture, dropwise adding 36 g (2.0 mol.) of water through the dropping funnel over five hours under nitrogen atmosphere, and then refluxing the mixture for an additional three hours. After refluxing the mixture, ether was distilled off and the starting material, methylphenyl dichlorosilane (184 g; 0.96 mol.) was recovered by distilling the reaction mixture in vacuo to obtain 220 g (0.67 mol.) of 1,3-dimethyl-1,3-diphenyl dichlorodisiloxane. Boiling Point=135°-138° C./2 mmHg.
Reaction SMILES: [C:1](=[O:43])([O:14][CH2:15]/[C:16](/[C:33]1[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=1)=[C:17](/[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)\[CH2:18][O:19][Si](C(C)(C)C)(C)C)[O:2][CH2:3][CH:4]([O:10][N+:11]([O-:13])=[O:12])[CH2:5][O:6][N+:7]([O-:9])=[O:8]>CC#N.C1(C)C=CC=CC=1>[C:1](=[O:43])([O:14][CH2:15]/[C:16](/[C:33]1[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:40])=[O:41])=[CH:35][CH:34]=1)=[C:17](/[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)\[CH2:18][OH:19])[O:2][CH2:3][CH:4]([O:10][N+:11]([O-:13])=[O:12])[CH2:5][O:6][N+:7]([O-:9])=[O:8]
Reactant: CC(C)(C)[Si](C)(C)OC/C(=C(\COC(=O)OCC(CO[N+](=O)[O-])O[N+](=O)[O-])c1ccc(S(C)(=O)=O)cc1)c1ccccc1
Solvent: Cc1ccccc1
Solvent: CC#N
Product: CS(=O)(=O)c1ccc(/C(COC(=O)OCC(CO[N+](=O)[O-])O[N+](=O)[O-])=C(/CO)c2ccccc2)cc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 101.1 %

Procedure:
To a 0° C. solution of 3.73 g of 2,3-bis(nitrooxy)propyl (2Z)-4-{[tert-butyl(dimethyl)silyl]oxy}-2-[4-(methylsulfonyl)phenyl]-3-phenylbut-2-en-1-yl carbonate in 150 mL of MeCN was added 5 mL of 70% PyHF. The resultant mixture was allowed to warm to rt and stirred for an additional 4 h. The reaction mixture was diluted with 600 mL of toluene and filtered through a plug of silica gel, eluting with EtOAc. The filtrate was concentrated and the resulting residue was further purified by flash chromatography over silica gel (10-50% EtOAc/hexane) to afford 3.1 g of the title compound along with a 20% impurity. 1H NMR of major compound (500 MHz, acetone-d6): δ 7.72 (d, 2H), 7.37 (d, 2H), 7.17-7.11 (m, 5H), 5.79-5.73 (m, 1H), 5.38 (s, 2H), 5.05 (dd, 1H), 4.87 (dd, 1H), 4.68-4.65 (m, 3H), 4.49 (dd, 1H), 4.15 (t, 1H), 3.05 (s, 3H).
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:17])/[CH:5]=[CH:6]/[C@H:7]1[CH2:12][CH2:11][C@H:10]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:9][CH2:8]1)[CH3:2]>[Pd].CCO>[CH2:1]([O:3][C:4](=[O:17])[CH2:5][CH2:6][C@H:7]1[CH2:8][CH2:9][C@H:10]([C:13]([CH3:16])([CH3:15])[CH3:14])[CH2:11][CH2:12]1)[CH3:2]
Reactant: CCOC(=O)/C=C/[C@H]1CC[C@H](C(C)(C)C)CC1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CC[C@H]1CC[C@H](C(C)(C)C)CC1

Procedure:
A suspension of trans-(E)-3-[4-(1,1-dimethylethyl)cyclohexyl]-2-propenoic acid ethyl ester (3.6 g, 15.1 mmol) in abs. EtOH (388 mL) and 5% Pd/C (1.4 g) was hydrogenated at 1 atm for 2 h. The catalyst was filtered over Celite and the filtrate and washings were concentrated to dryness to give trans-4-(1,1-dimethylethyl)cyclohexanepropanoic acid ethyl ester (3.58 g, 14.9 mmol) in 99% yield.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][C:3]=1[N+:15]([O-])=O>[C].[Pd].C1COCC1.CCO>[NH2:15][C:3]1[CH:4]=[C:5]([CH:8]([CH3:14])[C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:6]=[CH:7][C:2]=1[NH2:1]
Reactant: CCOC(=O)C(C)c1ccc(N)c([N+](=O)[O-])c1
Agent: [Pd]
Solvent: C1CCOC1
Solvent: CCO
Product: CCOC(=O)C(C)c1ccc(N)c(N)c1
Reaction time: 3 h

Procedure:
To the flask was added THF/EtOH (1:1, 50 mL) followed by Ethyl 2-(4-amino-3-nitrophenyl)propanoate (2.12 g, 8.90 mmol) and 10% palladium carbon (220 mg) at room temperature. The reaction mixture was hydrogenated and stirred for 3 hrs at 45 psi then filtered through celite bed, and washed with EtOH. The filtrate was concentrated in vacuo. The residue was purified by flash column chromatography on silica gel using EtOAc:hexanes (1:4-1:2) as eluant.
Reaction SMILES: [OH-].[K+].[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][OH:10].[Cl:11][C:12]1[CH:13]=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[CH:16][C:17]=1F.O>C(#N)C>[Cl:11][C:12]1[CH:13]=[C:14]([N+:19]([O-:21])=[O:20])[CH:15]=[CH:16][C:17]=1[O:10][CH2:9][C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][N:3]=1
Reactant: OCc1ccccn1
Reactant: O=[N+]([O-])c1ccc(F)c(Cl)c1
Agent: [K+]
Agent: [OH-]
Solvent: CC#N
Solvent: O
Product: O=[N+]([O-])c1ccc(OCc2ccccn2)c(Cl)c1
Temperature: 35 °C
Reaction time: 0.5 h
Yield: 69.6 %

Procedure:
A mixture of potassium hydroxide (20.6 g, 0.15 mol, 0.52 equiv) and 2-pyridylcarbinol (31.08 g, 0.285 mol, 1.00 equiv) in acetonitrile (750 ml) was stirred at 35° C. for 30 minutes. A solution of the 3-chloro-4-fluoronitrobenzene (50 g, 0.29 mol, 1.00 equiv) in acetonitrile (250 ml) was added and the mixture was stirred at 40° C. for 14 hours and then cooled to room temperature. Water (1000 ml) was added and the precipitated solids were filtered and washed with water and dried to give product 52.5 g. MS (ESI) m/z: 265 (M+1).
Reaction SMILES: CO[C:3]([CH3:5])=[CH2:4].[Br:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([OH:16])=[C:12]([CH2:17][OH:18])[CH:11]=1)=[O:9].C1(C)C=CC(S(O)(=O)=O)=CC=1>C(Cl)Cl>[Br:6][CH2:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]2[O:16][C:3]([CH3:5])([CH3:4])[O:18][CH2:17][C:12]=2[CH:11]=1)=[O:9]
Reactant: C=C(C)OC
Reactant: O=C(CBr)c1ccc(O)c(CO)c1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: ClCCl
Product: CC1(C)OCc2cc(C(=O)CBr)ccc2O1
Yield: 82.5 %

Procedure:
2-Methoxypropene (10 g) was added over 15 min to a stirred solution of 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)phenyl]ethanone (5 g) and toluene-4-sulphonic acid (0.5 g) in CH2Cl2 (100 ml) at 23°. The mixture was stirred for 3h, filtered through a wad of triethylamine-deactivated silica and evaporated to give an oil. Purification by [FCTS] (300 g) [E] afforded the title compound as an oil (4.8 g) with solidified on cooling. A small sample was crystallised from light petroleum (b.p. 60-80°) to give white crystals m.p. 47-48°.
Reaction SMILES: C([O:4][CH2:5][C:6]1[O:12][C:9]([CH:10]=[O:11])=[CH:8][CH:7]=1)(=O)C.C(O)(=[O:15])C>>[CH:10]([C:9]1[O:12][C:6]([C:5]([OH:4])=[O:15])=[CH:7][CH:8]=1)=[O:11]
Reactant: CC(=O)O
Reactant: CC(=O)OCc1ccc(C=O)o1
Product: O=Cc1ccc(C(=O)O)o1

Procedure:
5-HMF feed is oxidized with elemental O2 in a multi-step reaction to form FDCA with 5-formyl furan-2-carboxylic acid (FFCA) as a key intermediate eq 1. Oxidation of 5-(acetoxymethyl)furfural (5-AMF), which contains an oxidizable ester and aldehydes moieties, produces FDCA, FFCA, and acetic acid, eq 2. Similarly oxidation of 5-(ethoxymethyl)furfural (5-EMF) produces FDCA, FFCA, 5-(ethoxycarbonyl)furan-2-carboxylic acid (EFCA) and acetic acid, eq 3.
Reaction SMILES: C1(=O)[N:5]([CH2:6][CH2:7][CH2:8][O:9][C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:17]([CH3:23])[CH2:18][C:19](=[O:22])[NH:20][N:21]=3)=[CH:12][CH:11]=2)C(=O)C2=CC=CC=C12.O.NN.C1(=O)NC(=O)C2=CC=CC=C12.NN>CO.C(Cl)(Cl)Cl.C(O)C>[NH2:5][CH2:6][CH2:7][CH2:8][O:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:17]([CH3:23])[CH2:18][C:19](=[O:22])[NH:20][N:21]=2)=[CH:14][CH:15]=1
Reactant: CC1CC(=O)NN=C1c1ccc(OCCCN2C(=O)c3ccccc3C2=O)cc1
Agent: NN
Agent: O=C1NC(=O)c2ccccc21
Solvent: O
Solvent: CCO
Solvent: CO
Product: CC1CC(=O)NN=C1c1ccc(OCCCN)cc1
Yield: 79.7 %

Procedure:
A mixture of 0.997 g (2.55 mmol) of the phthalimide prepared above, 124 microliters (2.55 mmol) of 98% hydrazine monohydrate, and 25 ml of ethanol is heated at reflux under N2 overnight. TLC (90:10 CHCl3 :CH3OH) of the reaction mixture showed some phthalimide still present. An additional 25 ml of hydrazine was added, and the mixture heated at reflux for 3 hrs. The solvent is removed under vacuum, the residue taken up in about 10 ml of CH3OH and flash chromatographed on silica gel (90:10:2 CHCl3 :CH3OH:NH4OH) to give 531 mg of 6-[4-(3-aminopropyloxy)phenyl]-5-methyl-4,5-dihydro-3(2H)pyridazinone as a white solid. Yield 80%.
Reaction SMILES: [NH2:1][C:2]1[NH:6][N:5]=[C:4]([S:7](Cl)(=[O:9])=[O:8])[N:3]=1.[Cl:11][C:12]1[C:18]([CH3:19])=[CH:17][CH:16]=[C:15]([Cl:20])[C:13]=1[NH2:14]>>[Cl:11][C:12]1[C:18]([CH3:19])=[CH:17][CH:16]=[C:15]([Cl:20])[C:13]=1[NH2:14].[NH2:1][C:2]1[NH:6][N:5]=[C:4]([S:7]([NH:14][C:13]2[C:15]([Cl:20])=[CH:16][CH:17]=[C:18]([CH3:19])[C:12]=2[Cl:11])(=[O:9])=[O:8])[N:3]=1
Reactant: Nc1nc(S(=O)(=O)Cl)n[nH]1
Agent: Cc1ccc(Cl)c(N)c1Cl
Product: Cc1ccc(Cl)c(NS(=O)(=O)c2n[nH]c(N)n2)c1Cl
Temperature: 120 °C
Yield: 90.8 %

Procedure:
9.1 g (0.05 mol) of 5-amino-3-chlorosulfonyl-1,2,4-triazole (83.7% purity) are added in portions under argon over 1 hour to a melt of 22 g (0.125 mol) of 2,6-dichloro-3-methylaniline heated to 120° C. and stirred, and the suspension is stirred for 90 minutes at this temperature. After a similar work-up to example 1, 14.8 g (99.0% purity) of 2,6-dichloro-3-methylaniline and 13.5 g (90.8% purity) of 5-amino-N-(2,6-dichloro-3-methylphenyl)-1,2,4-triazole-3-sulfonamide are obtained. The theoretical yield is found to be 90.9%, and based on unrecovered aniline the yield is 98.1% of theory.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH2:15][O:16][CH2:17][CH2:18]Cl)=[CH:12][CH:13]=2)[C:8]([S:20]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][CH:24]=2)(=[O:22])=[O:21])=[N:7]1.[CH3:36][NH:37][CH3:38]>CS(C)=O.O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:33]=[CH:34][CH:35]=1)[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][C:11]([CH2:15][O:16][CH2:17][CH2:18][N:37]([CH3:38])[CH3:36])=[CH:12][CH:13]=2)[C:8]([S:20]([C:23]2[C:32]3[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=3)[CH:26]=[CH:25][CH:24]=2)(=[O:21])=[O:22])=[N:7]1
Reactant: CNC
Reactant: O=S(=O)(c1cccc2ccccc12)c1nn(Cc2cccc(Cl)c2)c2ccc(COCCCl)cc12
Solvent: O
Solvent: CS(C)=O
Product: CN(C)CCOCc1ccc2c(c1)c(S(=O)(=O)c1cccc3ccccc13)nn2Cc1cccc(Cl)c1
Temperature: 100 °C
Reaction time: 4 h
Yield: 93.7 %

Procedure:
A mixture of 1-(3-chlorobenzyl)-5-(2-chloroethoxymethy)-3-(1-naphthylsulfony)-1H-indazole (0.08 g, 0.16 mmoles) and dimethylamine (0.28 ml, 0.56 mmoles) in DMSO (1 mL) was stirred under nitrogen at 100° C. for 4 hours. Mixture was cooled to room temperature, diluted with water, extracted with EtOAc, washed with water (2×), brine (1×), dried over Na2SO4, and concentrated under vacuum. Compound was purified by flash chromatography using as eluent 5% CH3OH/EtOAc to afford the title compound (0.08 g, 0.15 mmoles).
Reaction SMILES: C[N+]([O-])=O.[C:5]1([C:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.N1C=CC=CC=1.[OH:23]O>C(Cl)Cl>[C:5]1([C:11]23[O:23][CH:12]2[CH2:13][CH2:14][CH2:15][CH2:16]3)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1
Reactant: OO
Reactant: C1=C(c2ccccc2)CCCC1
Solvent: c1ccncc1
Solvent: ClCCl
Solvent: C[N+](=O)[O-]
Product: c1ccc(C23CCCCC2O3)cc1
Reaction time: 6 h
Yield: 91 %

Procedure:
The wide scope of this process is revealed in FIGS. 5-8 and 15-16. Due to practical considerations, we used CH2Cl2 as solvent for all examples even though CH3NO2 is slightly superior with regard to reaction rate. Standard experimental procedure (exemplified for the epoxidation of 1-phenyl-cyclohexene) is as follows: In a 50 mL flask equipped with a magnetic stirrer, 7.9 g (50 mmol) of 1-phenylcyclohexene and 63 mg (0.25 mmol, 0.5 mol %) of MTO are dissolved in 25 mL CH2Cl2. To this solution is added 0.48 mL (6 mmol, 12 mol %) of pyridine followed by 7.6 mL (75 mmol; 1.5 equivalents) of 30% aqueous H2O2 added dropwise from a syringe (circa 5-10 minutes). During the H2O2 -addition the temperature is kept at 20-25° C. by applying an external cooling bath. The reaction is complete after 6 h and the aqueous phase is separated and discarded. The remaining H2O2 in the yellow organic phase is decomposed to O2 and H2O by stirring with a catalytic amount of MnO2 (circa 5 mg). After the yellow color has completely disappeared the mixture is dried over Na2SO4, concentrated, and purified by filtration through a short column of silica gel which has been deactivated with NEt3. The column is washed with hexane/CH2Cl2 and concentration of the eluate affords 7.9 g (91%) of 1-phenyl-1,2-epoxycyclohexane as a colorless oil).
Reaction SMILES: [C:1]([S:11]C1C=CC=CC=1)(=[O:10])[CH:2]=[CH:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[Cl-].[Al+3].[Cl-].[Cl-]>>[O:10]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2][C:1]1=[S:11]
Reactant: O=C(C=Cc1ccccc1)Sc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Product: S=c1ccc2ccccc2o1
Temperature: 85 °C
Yield: 55 %

Procedure:
A mixture of S-phenyl thiocinnamate (14.0 g, 58.25 mmol) and aluminum chloride (39 g) was stirred and heated at 85° C. for 3 hours. The hot reaction mixture was poured carefully over ice, then was extracted with ethyl acetate (3×300 mL), washed with brine (200 mL), dried (MgSO4) and was concentrated. The residue was recrystallized from hexane-ethyl acetate to afford 5.2 g (52%) of the desired product as pale yellow crystals.
Reaction SMILES: C[O:2][C:3]([C:5]1[CH:6]=[CH:7][C:8]2[C:9](=[O:20])[C:10]3[C:15]([O:16][C:17]=2[CH:18]=1)=[CH:14][CH:13]=[C:12]([Br:19])[CH:11]=3)=[O:4].COC(C1C=CC2C(=O)C3C(OC=2C=1)=CC=CC=3)=O>>[Br:19][C:12]1[CH:11]=[C:10]2[C:15]([O:16][C:17]3[CH:18]=[C:5]([C:3]([OH:4])=[O:2])[CH:6]=[CH:7][C:8]=3[C:9]2=[O:20])=[CH:14][CH:13]=1
Reactant: COC(=O)c1ccc2c(=O)c3cc(Br)ccc3oc2c1
Agent: COC(=O)c1ccc2c(=O)c3ccccc3oc2c1
Product: O=C(O)c1ccc2c(=O)c3cc(Br)ccc3oc2c1

Procedure:
Using an adaptation of the method described in Procedure 5, substituting 7-bromo-9-oxo-9H-xanthene-3-carboxylic acid methyl ester, 2f for 9-oxo-9H-xanthene-3-carboxylic acid methyl ester, 4a, the title compound 7-bromo-9-oxo-9H-xanthene-3-carboxylic acid, 3f was obtained.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[C:4]([CH3:9])[CH:3]=1.[CH2:10]=[C:11]1[O:15][C:13](=[O:14])[CH2:12]1.NC1C=CC=C(C)C=1C>>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:13]([CH2:12][C:11]([CH3:10])=[O:15])=[O:14])=[C:4]([CH3:9])[CH:3]=1
Reactant: C=C1CC(=O)O1
Reactant: Cc1ccc(N)c(C)c1
Agent: Cc1cccc(N)c1C
Product: CC(=O)CC(=O)Nc1ccc(C)cc1C

Procedure:
After the pressure drop (column 1: approx. 45 mbar, column 2: approx. 25 mbar) und the temperature profile (73-77° C.) had stabilized, m-xylidine (16.9 kg/h) was fed to the 2nd plate and diketene (total 12.0 kg/h) to plate Nos. 14, 15 and 16 of the first column. The diketene feed was started only after the xylidine-containing reflux had reached plate No. 14.