Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [N+:1]([C:4]1[CH:11]=[CH:10][CH:9]=[CH:8][C:5]=1[CH:6]=O)([O-:3])=[O:2].[CH:12]1([NH:15][C:16](=[O:21])[CH2:17][C:18]([CH3:20])=[O:19])[CH2:14][CH2:13]1.N1CCCCC1.C(O)(=O)C>C1C=CC=CC=1>[CH:12]1([NH:15][C:16](=[O:21])[CH2:17][C:18]([CH:20]=[CH:6][C:5]2[CH:8]=[CH:9][CH:10]=[CH:11][C:4]=2[N+:1]([O-:3])=[O:2])=[O:19])[CH2:14][CH2:13]1
Reactant: CC(=O)CC(=O)NC1CC1
Reactant: O=Cc1ccccc1[N+](=O)[O-]
Solvent: c1ccccc1
Solvent: C1CCNCC1
Solvent: CC(=O)O
Product: O=C(C=Cc1ccccc1[N+](=O)[O-])CC(=O)NC1CC1
Yield: 75.8 %

Procedure:
o-Nitrobenzaldehyde (7.6 g, 0.05 mole) and acetoacetic cyclopropylamide (7.1 g, 0.05 mole) are dissolved in benzene (40 ml) and thereto are added piperidine (0.2 ml) and acetic acid (0.6 ml), and the mixture is refluxed for 2 hours and the produced water is removed. After the stoichiometic amount of water is distilled off, the reaction is stopped. After the reaction, the reaction mixture is washed with 5% hydrochloric acid and then with water, and the solvent is distilled off under reduced pressure, and to the residue is added diethyl ether, and the obtained crude crystals are recrystallized from ethanol to give the title compound (10.4 g, yield 75.6%) as colorless needles, m.p. 133°-134° C.
Reaction SMILES: [Ag:1].[C:2]([CH:5]([CH:7]([C:9]([O-:11])=[O:10])[OH:8])[OH:6])([O-:4])=[O:3].[Na+].[Na+]>>[C:2]([CH:5]([CH:7]([C:9]([O-:11])=[O:10])[OH:8])[OH:6])([O-:4])=[O:3].[Ag+2:1]
Reactant: [Ag]
Agent: O=C([O-])C(O)C(O)C(=O)[O-]
Agent: [Na+]
Product: [Ag+2]

Procedure:
This example illustrates the preparation of the silver coating solution that is used in Examples 5 and 6. Three (3) ml of a sodium tartrate solution (tartaric acid disodium salt dehydrate, obtained from Aldrich) dissolved in 20 ml distilled water) was added to 3 ml of a silver nitrate solution (silver nitrate dissolved in 10 ml distilled water) at 22° C. A white precipitate of silver tartrate formed rapidly. Concentrated ammonium hydroxide, 28% ammonia (obtained from EM Science), was added dropwise to the solution until the silver tartrate dissolved completely to give a clear solution of ammoniacal silver tartarate with a pH of approximately 12.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:7]([N+:10]([O-:12])=[O:11])=[CH:6][C:4]=1[NH2:5].[Cl:13][C:14]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:15]=1[C:16]([N:18]=[C:19]=[O:20])=[O:17].C(OCC)C>CN1CCCC1=O>[Cl:13][C:14]1[CH:24]=[C:23]([F:25])[C:22]([F:26])=[CH:21][C:15]=1[C:16]([NH:18][C:19]([NH:5][C:4]1[CH:6]=[C:7]([N+:10]([O-:12])=[O:11])[CH:8]=[CH:9][C:3]=1[O:2][CH3:1])=[O:20])=[O:17]
Reactant: COc1ccc([N+](=O)[O-])cc1N
Reactant: O=C=NC(=O)c1cc(F)c(F)cc1Cl
Solvent: CN1CCCC1=O
Solvent: CCOCC
Product: COc1ccc([N+](=O)[O-])cc1NC(=O)NC(=O)c1cc(F)c(F)cc1Cl
Reaction time: 0.25 h
Yield: 71.9 %

Procedure:
4.0 g (23.8 mmol) of 2-methoxy-5-nitroaniline were dissolved in 10 ml of N-methyl-2-pyrrolidinone, and 5.2 g (23.8 mmol) of 2-chloro-4,5-difluorobenzoyl isocyanate were added. Slight warming occurred. After 15 minutes at room temperature, diethyl ether was added, and the resulting precipitate was filtered off with suction. 6.6 g (79%) of the desired product were obtained.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[NH:8][CH:7]=[C:6]2[CH:13]1[CH2:18][CH2:17][N:16]([CH3:19])[CH2:15][CH2:14]1.[H-].[K+].[CH2:22](OS(C1C=CC(C)=CC=1)(=O)=O)[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.C1OCCOCCOCCOCCOCCOC1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]([CH2:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[CH:7]=[C:6]2[CH:13]1[CH2:14][CH2:15][N:16]([CH3:19])[CH2:17][CH2:18]1
Reactant: COc1cc(C)c2[nH]cc(C3CCN(C)CC3)c2c1
Reactant: Cc1ccc(S(=O)(=O)OCCc2ccccc2)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: [H-]
Agent: [K+]
Product: COc1cc(C)c2c(c1)c(C1CCN(C)CC1)cn2CCc1ccccc1
Yield: 14.7 %

Procedure:
By a method similar to Preparation 26, using 5-methoxy-7-methyl-3-(1-methylpiperidin-4-yl)-1H-indole (5.81 mmol, 1.50 g), 35% potassium hydride (5.81 mmol, 0.665 g), toluene-4-sulfonic acid phenethyl ester (5.81 mmole, 1.60 g), additional 18-crown-6 (5.22 mmol,1.38 g) and additional toluene-4-sulfonic acid phenethyl ester (2.90 mmole, 0.802 g) were added to afford 0.31 g (15%) of the title compound: mass spectrum (ion spray): m/z=363 (M+1).
Reaction SMILES: ClC1C=C(CCC[N:11]([C@H:25]2[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]2)[C:12](=[O:24])NC2SC(SCC(O)=O)=CN=2)C=CC=1.[CH3:32][C:33]1[CH:38]=[CH:37][C:36]([CH2:39][CH2:40][CH2:41][C:42](O)=O)=[CH:35][CH:34]=1.C([O:47][C:48](=[O:59])[C:49]([S:52][C:53]1[S:57][C:56]([NH2:58])=[N:55][CH:54]=1)([CH3:51])[CH3:50])C>>[CH3:51][C:49]([S:52][C:53]1[S:57][C:56]([NH:58][C:12]([N:11]([C@H:25]2[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]2)[CH2:42][CH2:41][CH2:40][CH2:39][C:36]2[CH:35]=[CH:34][C:33]([CH3:32])=[CH:38][CH:37]=2)=[O:24])=[N:55][CH:54]=1)([CH3:50])[C:48]([OH:47])=[O:59]
Reactant: C[C@H]1CC[C@H](N(CCCc2cccc(Cl)c2)C(=O)Nc2ncc(SCC(=O)O)s2)CC1
Reactant: CCOC(=O)C(C)(C)Sc1cnc(N)s1
Reactant: Cc1ccc(CCCC(=O)O)cc1
Product: Cc1ccc(CCCCN(C(=O)Nc2ncc(SC(C)(C)C(=O)O)s2)[C@H]2CC[C@H](C)CC2)cc1

Procedure:
The compound was prepared following an analogous procedure to the one described for the synthesis of {2-[-3-[3-(3-chloro-phenyl)-propyl]-3-(trans-4-methyl -cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid using 4-(4-methyl-phenyl)-butyric-acid and 2-(2-amino-thiazol-5-ylsulfanyl)-2-methyl-propionic acid ethyl ester.
Reaction SMILES: [Si:1]([O:8][CH2:9][C:10]1[NH:11][C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[N:18]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[H-].[Na+].[CH3:21]I>CN(C)C=O>[Si:1]([O:8][CH2:9][C:10]1[N:11]([CH3:21])[C:12]2[CH:17]=[CH:16][N:15]=[CH:14][C:13]=2[N:18]=1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]
Reactant: CC(C)(C)[Si](C)(C)OCc1nc2cnccc2[nH]1
Reactant: CI
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(CO[Si](C)(C)C(C)(C)C)nc2cnccc21

Procedure:
A procedure similar to that described in Preparation 59 was repeated, except that 7.4 g of 2-t-butyldimethylsilyloxymethyl-1H-imidazo[4,5-c]pyridine (prepared as described in Preparation 71), 1.23 g of sodium hydride (as a 55% by weight dispersion in mineral oil), 2.0 ml of methyl iodide and 200 ml of dimethylformamide were used, to give the title compound as a crude product. This crude product was purified by column chromatography through silica gel, using a 10:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 3.30 g of the title compound, melting at 93°-95° C.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[CH:10](=[O:13])[CH2:11][CH3:12]>>[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[C:11]([CH3:12])[CH:10]=[O:13])=[CH:4][CH:3]=1.[CH:6](=[O:7])[CH:5]=[CH2:4]
Reactant: O=Cc1ccc(Cl)cc1
Reactant: CCC=O
Product: C=CC=O
Product: CC(C=O)=Cc1ccc(Cl)cc1

Procedure:
aldol condensation of 4-chlorobenzaldehyde and propionaldehyde to produce 3-(4-chlorophenyl)-2-methylpropenal as a propenal derivative,
Reaction SMILES: [Cl:1][C:2]1[N:7]=[N:6][C:5]([NH:8][NH2:9])=[C:4]([CH3:10])[C:3]=1[CH3:11].[N:12]#[C:13][Br:14]>CCO.O>[BrH:14].[Cl:1][C:2]1[C:3]([CH3:11])=[C:4]([CH3:10])[C:5]2[N:6]([C:13]([NH2:12])=[N:9][N:8]=2)[N:7]=1
Reactant: Cc1c(Cl)nnc(NN)c1C
Reactant: N#CBr
Solvent: O
Solvent: CCO
Product: Br
Product: Cc1c(Cl)nn2c(N)nnc2c1C
Temperature: 25 °C
Reaction time: 6 h
Yield: 100.2 %

Procedure:
(6-Chloro-4,5-dimethylpyridazin-3-yl)hydrazine (W3.006; 12 g) was initially charged in EtOH (240 ml) and water (50 ml) while stirring at RT. Thereafter, cyanogen bromide (14.7 g) in a mixture of EtOH (120 ml) and water (25 ml) was slowly added dropwise at RT. After stirring at RT for 6 h, the mixture was left to stand overnight. Then the mixture was dried and the residue was purified using silica gel (80 g cartridge, DCM/methanol gradient of 0-20% in 60 min). 19.4 g of the title compound were obtained.
Reaction SMILES: [H-].[H-].[H-].[H-].[Li+].[Al+3].[CH2:7]([C:9]([C:14]1[C:18]2[CH:19]=[CH:20][CH:21]=[C:22]([O:23][CH3:24])[C:17]=2[O:16][CH:15]=1)(C)[C:10]([O-])=[O:11])C>C1COCC1>[CH3:24][O:23][C:22]1[C:17]2[O:16][CH:15]=[C:14]([CH:9]([CH3:7])[CH2:10][OH:11])[C:18]=2[CH:19]=[CH:20][CH:21]=1
Reactant: CCC(C)(C(=O)[O-])c1coc2c(OC)cccc12
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1cccc2c(C(C)CO)coc12
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred suspension of LiAlH4 (200 mg, excess) in THF at 0° C., ethyl(7-methoxy-1-benzofuran-3-yl)propanoate (1.24 g, 5 mmol) in THF (20 mL) was added slowly. After the addition, the reaction mixture was stirred at room temperature for 1 hr and quenched with saturated NH4Cl solution. The product was extracted with chloroform and washed well with water. It was dried over anhydrous MgSO4; filtered and concentrated. The product, 2-(7-methoxy-1-benzofuran-3-yl)-1-propanol, was obtained as white oil, was pure enough and taken to the next step without purification. Yield: 900 mg (87%); 207 (M+H).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[S:11][C:10]=1[C:17]([O:19]C)=[O:18])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>O1CCCC1.CO.O>[CH2:1]([O:8][C:9]1[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[S:11][C:10]=1[C:17]([OH:19])=[O:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1sc(C(C)C)cc1OCc1ccccc1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: CC(C)c1cc(OCc2ccccc2)c(C(=O)O)s1
Temperature: 22 °C
Reaction time: 72 h

Procedure:
1.16 g of methyl 3-benzyloxy-5-isopropyl-thiophene-2-carboxylate were dissolved in 10 ml of tetrahydrofuran (THF) and 10 ml of methanol, and a solution of 1.7 g of lithium hydroxide in 10 ml of water was added. The reaction mixture was stirred at 22° C. for 72 h. Methanol and THF were stripped off in the rotary evaporator. While cooling in ice, the reaction mixture was adjusted to pH=4 with 2 molar hydrochloric acid and extracted twice with 50 ml of ethyl acetate each time. The combined organic phases were dried over sodium sulfate and concentrated.
Reaction SMILES: Br[CH2:2][CH2:3][C@H:4]1[CH2:9][CH2:8][C@H:7]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[C:18]([F:27])[CH:17]=3)=[CH:12][CH:11]=2)[CH2:6][CH2:5]1.[Mg].Cl[Si:30]1([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[CH2:35][CH2:34][CH2:33][CH2:32][CH2:31]1>C1COCC1>[CH2:36]([Si@H:30]1[CH2:31][CH2:32][C@H:33]([CH2:2][CH2:3][C@H:4]2[CH2:9][CH2:8][C@H:7]([C:10]3[CH:15]=[CH:14][C:13]([C:16]4[CH:21]=[CH:20][C:19]([O:22][C:23]([F:26])([F:25])[F:24])=[C:18]([F:27])[CH:17]=4)=[CH:12][CH:11]=3)[CH2:6][CH2:5]2)[CH2:34][CH2:35]1)[CH2:37][CH2:38][CH2:39][CH3:40]
Reactant: Fc1cc(-c2ccc([C@H]3CC[C@H](CCBr)CC3)cc2)ccc1OC(F)(F)F
Reactant: CCCCC[Si]1(Cl)CCCCC1
Agent: [Mg]
Solvent: C1CCOC1
Product: CCCCC[Si@H]1CC[C@H](CC[C@H]2CC[C@H](c3ccc(-c4ccc(OC(F)(F)F)c(F)c4)cc3)CC2)CC1

Procedure:
44.5 g (0.1 mol) of 4-(trans-4-(2-bromoethyl)cyclohexyl)-3'-fluoro-4'-trifluoromethoxybiphenyl was dripped into a mixture of 2.5 g (0.11 mol) of magnesium and 300 ml of THF to obtain a Grignard's reagent. This solution was then dripped into a 500 ml THF solution of 20.5 g (0.1 mol) of 1-chloro-1-n-pentyl-silacyclohexane. After a conventional after treatment, 4-(trans-4-(2-(trans-4-n-pentyl-4-silacyclohexyl)ethyl)cyclohexyl)-3'-fluoro-4'-trifluoromethoxybiphenyl was obtained. The silacyclohexane rings of the product were a mixture of trans isomers and cis isomers. They were separated by means of chromatography to obtain 44.9 g (yield 84.1%) of the trans isomer.
Reaction SMILES: Cl.Cl.[NH2:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([NH2:10])=N)=[CH:6][CH:5]=1.C[N:14](C=O)C.[C:18]1(=[O:25])[O:24][C:22](=[O:23])[CH2:21][CH2:20][CH2:19]1>CN(C1C=CC=CN=1)C.N1C=CC=CC=1>[NH2:14][N:10]=[CH:8][C:7]1[CH:6]=[CH:5][C:4]([NH:3][CH:21]([CH:22]=[O:23])[CH2:20][CH2:19][C:18]([OH:24])=[O:25])=[CH:12][CH:11]=1
Reactant: O=C1CCCC(=O)O1
Reactant: N=C(N)c1ccc(N)cc1
Reactant: CN(C)C=O
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: c1ccncc1
Product: NN=Cc1ccc(NC(C=O)CCC(=O)O)cc1
Temperature: 100 °C
Reaction time: 2 h
Yield: 50 %

Procedure:
4-Aminobenzamidine di-HCl (1 g, 4.8 mmol) was added to dry DMF (20 mL). To this solution dry pyridine (5 mL) and glutaric anhydride (0.68 g, 5.3 mmol) followed by 10 mg dimethylaminopyridine (DMAP) were added. The product started to precipitate after heating for 1/2h at 100° C. Heating was continued for 2 hr and water (25 mL) was added after cooling to room temperature. An abundant precipitate was filtered and dried in a desiccator to give 0.8 g, 50% of product as a white solid: H NMR (d6 -DMSO) δ 1.95 (m, 2H), 2.4 (m, 2H), 2.5 (m, 2H), 7.85 (s, 4H), 9.05 (bs, 2H), 9.25 (bs, 2H), 10.4 (s, 1H), MS(FAB) m/e 250.1 (M+H+).
Reaction SMILES: [NH2:1][C:2]1[N:6]=[CH:5][NH:4][N:3]=1.Br[CH:8]([C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[CH3:9]>>[C:10]1([CH:8]([N:4]2[CH:5]=[N:6][C:2]([NH2:1])=[N:3]2)[CH3:9])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: Nc1nc[nH]n1
Reactant: CC(Br)c1ccccc1
Product: CC(c1ccccc1)n1cnc(N)n1

Procedure:
Prepared in analogy to example 3a) starting with 3-amino-1,2,4-triazole and (1-bromoethyl)benzene. The title compound was obtained as a colorless solid (Yield=10%). MS ISP (m/e): 189.2.0 (100) [(M+H)+].
Reaction SMILES: [CH3:1][CH:2]([S:4][C:5]1[NH:6][C:7]([C:18]2[CH:23]=[CH:22][N:21]=[CH:20][CH:19]=2)=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[CH:12][CH:11]=2)[N:9]=1)[CH3:3].ClC1C=CC=C(C(OO)=[O:32])C=1>C(Cl)Cl>[CH3:3][CH:2]([S:4]([C:5]1[NH:6][C:7]([C:18]2[CH:19]=[CH:20][N:21]=[CH:22][CH:23]=2)=[C:8]([C:10]2[CH:11]=[CH:12][C:13]([O:16][CH3:17])=[CH:14][CH:15]=2)[N:9]=1)=[O:32])[CH3:1]
Reactant: COc1ccc(-c2nc(SC(C)C)[nH]c2-c2ccncc2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: COc1ccc(-c2nc(S(=O)C(C)C)[nH]c2-c2ccncc2)cc1
Reaction time: 0.25 h

Procedure:
The 2-isopropylthioimidazole from Example 9 (11.1 g, 35 mmole) was suspended in 300 ml of methylene chloride and placed in an ice-bath. m-Chloroperbenzoic acid (7.5 g) was added in 100 ml. of methylene chloride over the period of 40 minutes. The solution was stirred for an additional 15 minutes and organic solution extracted with sodium bicarbonate (5%). The aqueous alkaline extract was discarded and the organic layer was dried and evaporated to give a semi-solid which was recrystallized from methylene chloride-ether yielding 7.5 g of a crystalline solid which was further purified by chromatography (alumina). The pure product was obtained from chloroform elution: 180°-181.5°.
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][CH2:10][CH2:11][CH2:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1.[Cl:19][CH2:20][C:21](Cl)=[O:22]>ClCCl>[Cl:19][CH2:20][C:21]([N:9]([C:3]1[C:2]([CH3:1])=[CH:7][CH:6]=[CH:5][C:4]=1[CH3:8])[CH2:10][CH2:11][CH2:12][C:13]1[CH:14]=[N:15][CH:16]=[CH:17][CH:18]=1)=[O:22]
Reactant: Cc1cccc(C)c1NCCCc1cccnc1
Reactant: O=C(Cl)CCl
Solvent: ClCCl
Product: Cc1cccc(C)c1N(CCCc1cccnc1)C(=O)CCl
Temperature: 25 °C

Procedure:
A solution of 10.0 g of N-(2,6-dimethylphenyl)-3-pyridinepropanamine in 75 ml of dichloromethane was added dropwise to a cold (20° C.) solution of 3.5 ml of chloroacetylchloride in 35 ml of dichloromethane. The cooling bath was removed and the reaction was allowed to warm to room temperature over 30 minutes followed by the addition of excess aqueous sodium bicarbonate solution. The layers were separated and the organic layer was washed with brine, dried with sodium sulfate and evaporated to give 13.4 g of product as a dark oil which was used directly in the next steps, that is, in Examples 20 and 21.
Reaction SMILES: [N+:1]1([O-])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:8]1([CH3:25])[CH:13]=[CH:12][C:11]([S:14]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:16])=[O:15])=[CH:10][CH:9]=1>>[C:8]1([CH3:25])[CH:9]=[CH:10][C:11]([S:14]([O-:17])(=[O:15])=[O:16])=[CH:12][CH:13]=1.[CH2:18]([O:17][N+:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=1
Reactant: [O-][n+]1ccccc1
Reactant: Cc1ccc(S(=O)(=O)OCc2ccccc2)cc1
Product: Cc1ccc(S(=O)(=O)[O-])cc1
Product: c1ccc(CO[n+]2ccccc2)cc1

Procedure:
N-Benzyloxypyridinium p-toluenesulfonate was prepared by mixing pyridine-N-oxide and an equimolar amount of benzyl p-toluenesulfonate and heating the mixture at 85°C for 4 hours. The crude product was recrystallized from a mixture of ethanol and ethyl acetate. By this procedure N-benzyloxypyridinium p-toluenesulfonate having a melting point of 107° to 109°C was obtained.
Reaction SMILES: [C:1]([O:4][C@H:5]1[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@H:9]([CH3:20])[O:8][CH:6]1[OH:7])(=[O:3])[CH3:2].[Cl-].[Li+].N12CCCN=C1CCCCC2.[Cl:34][C:35]([Cl:39])([Cl:38])[C:36]#[N:37]>C(#N)C>[Cl:34][C:35]([Cl:39])([Cl:38])[C:36](=[NH:37])[O:7][C@H:6]1[O:8][C@@H:9]([CH3:20])[C@@H:10]([O:16][C:17](=[O:19])[CH3:18])[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@@H:5]1[O:4][C:1](=[O:3])[CH3:2]
Reactant: N#CC(Cl)(Cl)Cl
Reactant: CC(=O)O[C@@H]1[C@H](OC(C)=O)[C@H](C)OC(O)[C@H]1OC(C)=O
Agent: [Cl-]
Agent: [Li+]
Solvent: C1CCC2=NCCCN2CC1
Solvent: CC#N
Product: CC(=O)O[C@H]1[C@H](OC(C)=O)[C@@H](OC(=N)C(Cl)(Cl)Cl)O[C@@H](C)[C@H]1OC(C)=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 92 %

Procedure:
A mixture of 2,3,4-tri-O-acetyl-L-fucopyranose (anomer mixture) (0.50 g, 1.72 mmol), lithium chloride (73 mg, 1.72 mmol), 1,8-diazabicyclo-[5.4.0]-undec-7-ene (0.20 ml, 1.34 mmol) and trichloroacetonitrile (2.0 ml, 20 mmol) in 20 ml of dry acetonitrile is stirred under nitrogen and at room temperature for about 12 h. After chromatographic purification (petroleum ether/diethyl ether 2:5), a mixture of O-(2,3,4-tri-O-acetyl-α-L-fucopyranosyl) trichloroacetimidate (3) and O-(2,3,4-tri-O-acetyl-β-L-fucopyranosyl) trichloroacetimidate (2) is obtained in a yield of 92% (α:β=6.5:1).
Reaction SMILES: O=[O+][O-].O=O.O=[O+][O-].[C:9]1([CH:15]([O:22][C:23](=[O:55])[CH:24]([N:28]2[CH:31]([S:32][S:33][C:34]3[O:35][C:36]4[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=4[N:38]=3)[CH:30]([NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:29]2=[O:54])[C:25](=C)[CH3:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C1(C)C=CC=CC=1.C(OCC)(=[O:65])C>C(OCC)(=O)C>[C:9]1([CH:15]([O:22][C:23](=[O:55])/[C:24](/[N:28]2[CH:31]([S:32][S:33][C:34]3[O:35][C:36]4[CH:42]=[CH:41][CH:40]=[CH:39][C:37]=4[N:38]=3)[CH:30]([NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=3)[C:29]2=[O:54])=[C:25](\[OH:65])/[CH3:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1
Reactant: C=C(C)C(C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)C(NC(=O)COc2ccccc2)C1SSc1nc2ccccc2o1
Reactant: CCOC(C)=O
Agent: O=O
Agent: O=[O+][O-]
Solvent: Cc1ccccc1
Product: C/C(O)=C(/C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)C(NC(=O)COc2ccccc2)C1SSc1nc2ccccc2o1

Procedure:
(aix) Approximately one equivalent of ozone (in the form of an O2 /O3 mixture) is passed into a solution, cooled to -70° C., of 3.35 g of 2-[4-(benzoxazol-2-yldithio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-methylene-butyric acid diphenylmethyl ester in 125 ml of ethyl acetate, until starting material is no longer detectable by thin layer chromatography (silica gel; toluene/ethyl acetate, 3:1). The solution is concentrated by evaporation to about 50 ml in vacuo, mixed with 5 ml of dimethyl sulphide and stirred until the potassium iodide/starch test no longer gives a reaction. The mixture is concentrated by evaporation in vacuo, the residue is dissolved in 150 ml of benzene and the solution is washed with water. The organic phase is dried over sodium sulphate and concentrated by evaporation. The residue is chromatographed on 150 g of acid-washed silica gel, using toluene/ethyl acetate, 4:1. 2-[4-(Benzoxazol-2-yldithio)-3-phenoxyacetamido-2-oxoazetidin-1-yl]-3-hydroxy-crotonic acid diphenylmethyl ester is obtained in the form of a white foam; IR spectrum (methylene chloride): characteristic bands at 5.60, 5.90 and 6.0μ.
Reaction SMILES: C(N(CC)C(C)C)(C)C.[F:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[CH2:21][CH2:20][CH2:19][C:18]=1[CH2:22]O.CS([Cl:28])(=O)=O.O>ClCCl>[Cl:28][CH2:22][C:18]1[CH2:19][CH2:20][CH2:21][C:17]=1[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[F:10]
Reactant: CS(=O)(=O)Cl
Reactant: OCC1=C(c2ccccc2F)CCC1
Solvent: ClCCl
Solvent: O
Solvent: CCN(C(C)C)C(C)C
Product: Fc1ccccc1C1=C(CCl)CCC1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
N,N-Diisopropylethylamine (17.2 mL) was added to a solution of [2-(2-fluorophenyl)cyclopent-1-enyl]methanol obtained in Preparation Example 3-(3) (6.50 g) in dichloromethane (300 mL) in an ice bath. Methanesulfonyl chloride (2.88 mL) was added to the reaction solution at the same temperature. Then, the reaction solution was warmed to room temperature and stirred overnight. Water was added to the reaction mixture, followed by extraction with chloroform. The organic layer was dried over anhydrous magnesium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain the title compound (7.23 g).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([SH:10])=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH2:11]([N:13](CC)CC)[CH3:12].BrCC#N.O>C1COCC1>[N+:1]([C:4]1[CH:9]=[CH:8][C:7]([S:10][CH2:12][C:11]#[N:13])=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: CCN(CC)CC
Reactant: O=[N+]([O-])c1ccc(S)cc1
Agent: N#CCBr
Solvent: O
Solvent: C1CCOC1
Product: N#CCSc1ccc([N+](=O)[O-])cc1

Procedure:
4-nitrobenzenethiol (10 g) was dissolved in THF (100 ml), and to this solution was added triethylamine (12.6 ml) and then, bromoacetonitrile (5.4 ml), and the mixture was stirred for 30 minutes. The reaction solution was added to water, and extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure and the obtained residue was washed with hexane/ethyl acetate, to give 2-[(4-nitrophenyl)sulfanyl]acetonitrile (10.3 g).
Reaction SMILES: [N:1]([O-])=O.[Na+].[CH2:5]([O:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[CH:15][CH:14]=1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.O.O.[Cl:22][Sn]Cl>>[ClH:22].[CH2:5]([O:12][C:13]1[CH:14]=[CH:15][C:16]([NH:17][NH2:1])=[CH:18][CH:19]=1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1
Reactant: O=N[O-]
Reactant: Nc1ccc(OCc2ccccc2)cc1
Reactant: Cl[Sn]Cl
Agent: [Na+]
Solvent: O
Product: Cl
Product: NNc1ccc(OCc2ccccc2)cc1
Temperature: 0 °C
Yield: 94.3 %

Procedure:
A solution of sodium nitrite (3.8 g, 0.055 mol in 20 mL of H2O), is added dropwise to an ice cold stirring suspension of 4-benzyloxyaniline (13.0 g, 0.055 mol in 150 mL of concentrated HCl). The reaction mixture is stirred for 90 minutes at -8° to 10° C. A solution of SnCl2.2H2O (32.0 g, 0142 mol in 50 mL concentrated HCl) is added and stirred for 1 hour at 0° C. The reaction mixture is removed from the ice bath and is stirred at room temperature for 20 hours. The mixture is then filtered and washed with water to give 13.0 g (95% yield) of product, m.p. 182°-185° C.