Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[CH2:2][CH2:3][CH:4]1[CH2:10][N:9]([CH3:11])[C:8](=[O:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[O:5]1.[CH3:17][CH:18]1[CH2:22][CH2:21][CH2:20][NH:19]1>C(O)C>[CH3:11][N:9]1[C:8](=[O:12])[C:7]2[CH:13]=[CH:14][CH:15]=[N:16][C:6]=2[O:5][CH:4]([CH2:3][CH2:2][N:19]2[CH2:20][CH2:21][CH2:22][CH:18]2[CH3:17])[CH2:10]1
Reactant: CC1CCCN1
Reactant: CN1CC(CCCl)Oc2ncccc2C1=O
Solvent: CCO
Product: CC1CCCN1CCC1CN(C)C(=O)c2cccnc2O1
Yield: 35.7 %

Procedure:
To a solution of 3.5 g (0.0145 mole) of 2-(2-chloroethyl)-2,3-dihydro-4-methylpyrido[3,2-f][1,4]oxazepine-5(4H)-one in ethanol (15 ml) was added 2-methyl pyrrolidine (5.0 g, 0.063 mole). The solution was heated to reflux for 3 hours with stirring. The ethanol was removed by rotary evaporation (water aspirator, 80° C.). The residual oil was partitioned between dilute aqueous sodium hydroxide (50 ml) and chloroform (50 ml). The organic layer was saved and the aqueous layer extracted with chloroform (2×30 ml). All the chloroform layers were combined, dried over anhydrous sodium sulfate and concentrated by rotary evaporation (water aspirator, 70° C.). The residual oil was then distilled at 200° C. and low vacuum (vacuum pump) giving 1.5 g (36.7%) of a clear oil.
Reaction SMILES: CS(C)=O.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH:13](Br)([CH2:15][CH3:16])[CH3:14].[OH:18][C:19]1[C:28]([OH:29])=[C:27]2[C:22]([C:23](=[O:32])[CH2:24][C:25]([CH3:31])([CH3:30])[O:26]2)=[CH:21][CH:20]=1>COCCOCCOC>[CH:13]([O:18][C:19]1[C:28]([OH:29])=[C:27]2[C:22]([C:23](=[O:32])[CH2:24][C:25]([CH3:30])([CH3:31])[O:26]2)=[CH:21][CH:20]=1)([CH2:15][CH3:16])[CH3:14]
Reactant: CCC(C)Br
Reactant: CC1(C)CC(=O)c2ccc(O)c(O)c2O1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CS(C)=O
Solvent: COCCOCCOC
Product: CCC(C)Oc1ccc2c(c1O)OC(C)(C)CC2=O
Temperature: 100 °C
Reaction time: 2 h
Yield: 83 %

Procedure:
In 80 ml of dimethyl sulfoxide 4.2 g (20 millimoles) of 7.8-dihydroxy-2,2-dimethyl-4-chromanone are dissolved, whereupon 10 ml of diethylene glycol dimethylether, 4.1 g (30 millimoles) of potassium carbonate, 0.5 g of potassium iodide and 3.3 (2.6 ml, 24 millimoles) of sec. butyl bromide are added. The reaction mixture is heated at 100° C. for 10 hours, poured onto 200 ml of crushed ice and extracted with 100 ml of carbon tetrachloride. To the aqueous phase 20 ml of 10% sodium hydroxide solution are added, the mixture is cooled to 0° C., acidified with concentrated hydrochloric acid and stirred at 0° C. for 2 hours. The product is filtered, washed twice with 20 ml of water, dried and crystallized from 20% ethanol. Thus 4.4. g of the desired compound are obtained, yield 83%, mp.: 108°-110° C.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12](=[O:18])[C:13]([N:15]([CH3:17])[NH2:16])=[O:14])[CH3:2].[CH3:19][S:20][CH2:21][C:22](=O)[CH3:23]>O1CCCC1>[CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12](=[O:18])[C:13]([N:15]([CH3:17])[N:16]=[C:22]([CH3:23])[CH2:21][S:20][CH3:19])=[O:14])[CH3:2]
Reactant: CSCC(C)=O
Reactant: CCc1cc(C)cc(CC)c1C(=O)C(=O)N(C)N
Solvent: C1CCOC1
Product: CCc1cc(C)cc(CC)c1C(=O)C(=O)N(C)N=C(C)CSC
Temperature: 25 °C
Reaction time: 22 h
Yield: 86.1 %

Procedure:
To a 20 ml volume two-necked flask, 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-39) (0.50 g), tetrahydrofuran (anhydrous) (9 ml), and 1-methylsulfanyl-2-propanone (7-0-1) (0.23 g) were added and stirred at room temperature for 22 hours under a nitrogen atmosphere. Additional 1-methylsulfanyl-2-propanone (7-0-1) (0.12 g) was added thereto, and the mixture was further stirred at room temperature for 7 hours. Then, the reaction mixture was concentrated under reduced pressure. After the concentration, the residue was subjected to column chromatography (hexane:ethyl acetate=1:1) to gave 0.58 g of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(1-methylsulfanyl-2-propylidene)hydrazine ((4-4)-(1)-39).
Reaction SMILES: [N:1]1([C:7]2[S:8][CH:9]=[C:10]([CH2:12][OH:13])[N:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(N(CC)CC)C>CS(C)=O>[N:1]1([C:7]2[S:8][CH:9]=[C:10]([CH:12]=[O:13])[N:11]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: OCc1csc(N2CCCCC2)n1
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Product: O=Cc1csc(N2CCCCC2)n1

Procedure:
The reaction described in Preparation 44 was repeated, but using 2.4 g of 2-piperidinothiazol-4-ylmethanol, 5.8 g of sulfur trioxide pyridine complex, 3.7 g of triethylamine and 30 ml of dimethyl sulfoxide, giving the title compound as pale orange prisms.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[C:9]([C:17](=[O:19])[CH3:18])[C:10]([OH:16])=[CH:11][CH:12]=2)[CH:7]=1.[Br:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]Br.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH3:1][O:2][C:3](=[O:20])[CH2:4][O:5][C:6]1[CH:15]=[CH:14][C:13]2[C:8](=[C:9]([C:17](=[O:19])[CH3:18])[C:10]([O:16][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][Br:21])=[CH:11][CH:12]=2)[CH:7]=1
Reactant: BrCCCCCBr
Reactant: COC(=O)COc1ccc2ccc(O)c(C(C)=O)c2c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: COC(=O)COc1ccc2ccc(OCCCCCBr)c(C(C)=O)c2c1
Yield: 100.1 %

Procedure:
A mixture of 1.1 g of [[8-acetyl-7-hydroxy-2-naphthalenyl]oxy]acetic acid methyl ester, 9.2 g of 1,5-dibromopentane and 0.83 g of anhydrous potassium carbonate in 30 ml of anhydrous acetone was stirred at reflux for 17 hours. The reaction mixture was filtered and filtrate was concentrated at 60° C./10.15 mm to an oil which was purified by flash column chromatography to yield 1.7 g of [[8-Acetyl-7-(5-bromopentyloxy)-2-naphthalenyl]oxy]acetic acid methyl ester as an oil.
Reaction SMILES: [CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N:3]=1.ClC1C=CC=C(C(OO)=[O:17])C=1>C(Cl)Cl>[CH3:1][C:2]1[C:7]([CH3:8])=[CH:6][CH:5]=[CH:4][N+:3]=1[O-:17]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: Cc1cccnc1C
Solvent: ClCCl
Product: Cc1ccc[n+]([O-])c1C

Procedure:
A solution of 24 g of 2,3-dimethylpyridine in 100 ml of methylene chloride was treated while cooling with ice with a solution of 46.6 g of m-chloroperbenzoic acid in 100 ml of methylene chloride. The reaction mixture was heated under reflux for 2 hours and concentrated in a rotary evaporator. The residue was chromatographed on silica gel with ethyl acetate/methylene chloride (3:1) as the elution agent, the medium pressure flash chromatography method being used and the pressure being produced with nitrogen gas. By recrystallization from ether there was obtained 2,3-dimethylpyridine 1-oxide of melting point 56°.
Reaction SMILES: [C:1]1([C:7]2[CH2:12][CH2:11][CH2:10][CH2:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([O-])(O)=[O:14].[Na+].OOS([O-])=O.[K+].O>C(#N)C.O>[C:1]1([C:7]23[O:14][CH:8]2[CH2:9][CH2:10][CH2:11][CH2:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C([O-])O
Reactant: C1=C(c2ccccc2)CCCC1
Agent: O=S([O-])OO
Agent: [K+]
Agent: [Na+]
Solvent: CC#N
Solvent: O
Product: c1ccc(C23CCCCC2O3)cc1
Reaction time: 2 h
Yield: 83 %

Procedure:
To a solution of phenyl cyclohexene (79 mg, 0.5 mmol) in a mixture of acetonitrile (4.5 ml) and water (2 drops) were added first finely crushed NaHCO3 (168 mg, 2 mmol) and oxone (307 mg, 0.5 mmol) then the catalyst (0.05 mmol). The resulting yellow suspension was allowed to react at RT, under good stirring. TLC was used to follow the reaction which indicated that the reaction was finished in 2 h. Water (3 ml) was added to the reaction mixture followed by extraction into methylene dichloride. The organic extracts were combined and dried over anhydrous sodium sulphate. Concentration on a rotary evaporator gave a material which was purified on a column using 2% ethyl acetate:petrol mixture as eluent to give the desired compound as a colourless oil. (72 mg, 83% yield, 70% e.e).
Reaction SMILES: C(O[C:6]([NH:8][CH2:9][CH:10]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]([C:21]2[C:30]3[O:29][CH2:28][CH2:27][N:26]([CH3:31])[C:25]=3[CH:24]=[C:23]([Cl:32])[CH:22]=2)=[O:20])[CH2:11]1)=[O:7])(C)(C)C.[NH2:33][C:34]1[C:42]([Cl:43])=[CH:41][C:37](C(O)=O)=[C:36]([O:44][CH3:45])[CH:35]=1>>[NH2:33][C:34]1[C:42]([Cl:43])=[CH:41][C:37]([C:6]([NH:8][CH2:9][CH:10]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][NH:18][C:19]([C:21]3[C:30]4[O:29][CH2:28][CH2:27][N:26]([CH3:31])[C:25]=4[CH:24]=[C:23]([Cl:32])[CH:22]=3)=[O:20])[CH2:11]2)=[O:7])=[C:36]([O:44][CH3:45])[CH:35]=1
Reactant: CN1CCOc2c(C(=O)NCCCN3CCC(CNC(=O)OC(C)(C)C)C3)cc(Cl)cc21
Reactant: COc1cc(N)c(Cl)cc1C(=O)O
Product: COc1cc(N)c(Cl)cc1C(=O)NCC1CCN(CCCNC(=O)c2cc(Cl)cc3c2OCCN3C)C1

Procedure:
N-(3-(3-tert-Butoxycarbonylaminomethylpyrrolidin-1-yl)propyl)-6-chloro-4-methyl-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide (1.5 g) as starting compound was reacted and treated in the same manner as in Example 67 using 4-amino-5-chloro-2-methoxybenzoic acid (0.65 g) to give N-(3-(3-(4-amino-5-chloro-2-methoxybenzoylaminomethyl)-pyrrolidin-1-yl)propyl)-6-chloro-4-methyl-3,4-dihydro-2H-1,4-benzoxazine-8-carboxamide.
Reaction SMILES: [S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7](Cl)=[O:8].[NH2:10][CH:11]1[C:26](=[O:27])[N:13]2[C:14]([C:23]([OH:25])=[O:24])=[C:15]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[CH2:16][S:17][C@:12]12[S:28][CH3:29].C([O-])(O)=O.[Na+]>O.CC(C)=O>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:10][CH:11]1[C:26](=[O:27])[N:13]2[C:14]([C:23]([OH:25])=[O:24])=[C:15]([CH2:18][O:19][C:20](=[O:22])[CH3:21])[CH2:16][S:17][C@:12]12[S:28][CH3:29])=[O:8]
Reactant: CS[C@]12SCC(COC(C)=O)=C(C(=O)O)N1C(=O)C2N
Reactant: O=C(Cl)Cc1cccs1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: CS[C@]12SCC(COC(C)=O)=C(C(=O)O)N1C(=O)C2NC(=O)Cc1cccs1
Temperature: 0 °C
Yield: 33.5 %

Procedure:
2-Thienylacetyl chloride (28 μl, 0.209 mMol) is added to an ice-cold, stirring mixture of 7-amino-6-methylthio-3-acetoxymethyl-ceph-3-em-4-carboxylic acid (66.4 mg., 0.209 mMol) and NaHCO3 (35 mg., 0.418 mMol) in H2O (1.5 ml.) and acetone (3.0 ml.). After stirring for 30 mins. in the cold, the mixture is evaporated under reduced pressure to remove acetone. The aqueous residue is diluted with more H2O (4.5 ml). and extracted with three portions of Et2O. The aqueous phase is acidified to pH 2.5 with 10% HCl and extracted with three portions of EtOAc. The EtOAc solution is dried over MgSO4, filtered, and evaporated in vacuo to a solid (72 mg.). This material is extracted with φH to remove 2-thienylacetic acid and the residue recrystallized from CH3CN-Et2O to provide 7-(2-thienylacetamido)-6-methylthio-3-acetoxymethyl-ceph-3-em-4-carboxylic acid (31 mg.) as an off-white solid.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][OH:14])[O:10][N:9]=2)=[CH:4][C:3]=1[F:15].C(N(CC)CC)C.[CH3:23][S:24](Cl)(=[O:26])=[O:25].C(=O)(O)[O-].[Na+]>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH2:12][CH:11]([CH2:13][O:14][S:24]([CH3:23])(=[O:26])=[O:25])[O:10][N:9]=2)=[CH:4][C:3]=1[F:15]
Reactant: OCC1CC(c2ccc(Br)c(F)c2)=NO1
Reactant: CS(=O)(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CS(=O)(=O)OCC1CC(c2ccc(Br)c(F)c2)=NO1
Temperature: 0 °C
Reaction time: 2 h
Yield: 97.8 %

Procedure:
[3-(4-Bromo-3-fluoro-phenyl)-4,5-dihydro-isoxazol-5-yl]-methanol (30 g, 112.4 mmol) was added to anhydrous dichloromethane (300 ml) followed by addition of triethylamine (21.8 ml, 157.3 mmol). The solution was cooled to 0° C. followed by drop wise addition of methane sulfonyl chloride (10.4 ml, 134.8 mmol). The reaction was stirred for 2 hours at 0° C. and then aqueous sodium bicarbonate (100 ml) was added. After further extraction with dichloromethane (2×100 ml), the organic layers were combined, dried over sodium sulfate, and concentrated in vacuo to give the desired product (38.7 g).
Reaction SMILES: [F:1][C:2]([F:23])([F:22])[C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH2:14][CH2:13][N:12](C(OC(C)(C)C)=O)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1.C(=O)(O)[O-].[Na+]>ClCCl.FC(F)(F)C(O)=O>[F:23][C:2]([F:1])([F:22])[C:3]1[CH:4]=[CH:5][C:6]([N:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:7][CH:8]=1
Reactant: CC(C)(C)OC(=O)N1CCN(c2ccc(C(F)(F)F)cc2)CC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: FC(F)(F)c1ccc(N2CCNCC2)cc1
Temperature: 30 °C
Reaction time: 2 h

Procedure:
A solution of t-butyl 4-(4-(trifluoromethyl)phenyl)piperazine-1-carboxylate (1.06 g, 3.21 mmol, 1.00 equiv) in dichloromethane (10 mL) and trifluoroacetic acid (6 mL) was placed in a 50-mL round-bottom flask and stirred for 2 h at 30° C. in an oil bath. The pH value of the solution was adjusted to 7-8 with saturated aqueous sodium bicarbonate. The resulting solution was extracted with 4×30 mL of dichloromethane and the organic layers combined and dried over anhydrous sodium sulfate, followed by filtration to remove the solids. The resulting solution was concentrated under vacuum, resulting in 740 mg (crude) of 1-(4-(trifluoromethyl)phenyl)piperazine as a yellow solid.
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:16])[CH2:11][CH2:10]2)[CH:4]=1)#[N:2].Cl.[OH:24][NH2:25].C(=O)([O-])[O-].[K+].[K+]>C(O)C>[NH2:2][C:1](=[N:25][OH:24])[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([N:9]2[CH2:10][CH2:11][N:12]([C:15]([O:17][CH2:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:16])[CH2:13][CH2:14]2)[CH:4]=1
Reactant: NO
Reactant: CC(C)(C)COC(=O)N1CCN(c2cc(C#N)ccn2)CC1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: CC(C)(C)COC(=O)N1CCN(c2cc(C(N)=NO)ccn2)CC1
Yield: 110.1 %

Procedure:
2,2-Dimethylpropyl 4-(4-cyanopyridin-2-yl)piperazine-1-carboxylate (1.67 g) obtained in Example 2 was dissolved in ethanol (10 mL), and hydroxyamine hydrochloride (1.17 g) and potassium carbonate (3.11 g) were added thereto, heated under reflux for 2 hours, and the solvent was evaporated away, the resulting residue was diluted with ethyl acetate, washed with water and saturated saline water, and dried with anhydrous sodium sulfate. The solvent was evaporated away to obtain 2.04 g of the entitled compound.
Reaction SMILES: [CH3:1][C:2]([S:7][CH3:8])([CH3:6])[CH:3]=[N:4][OH:5].[CH3:9][N:10]=[C:11]=[O:12]>>[CH3:9][NH:10][C:11]([O:5][N:4]=[CH:3][C:2]([CH3:6])([S:7][CH3:8])[CH3:1])=[O:12]
Reactant: CSC(C)(C)C=NO
Reactant: CN=C=O
Product: CNC(=O)ON=CC(C)(C)SC

Procedure:
A process for preparing 2-methyl-2-(methylsulfonyl) propionaldehyde 0-(methylcarbamoyl) oxime which comprises (i) reacting 2-methyl-2-(methylthio) propionaldehyde oxime with methyl isocyanate in the presence of an aqueous medium for a period sufficient to form 2-methyl-2-(methylthio) propionaldehyde O-(methylcarbamoyl) oxime and (ii) reacting 2-methyl-2-(methylthio) propionaldehyde 0-(methylcarbamoyl) oxime with a mixture of hydrogen peroxide and a carboxylic acid in the presence of a substantially aqueous medium and a catalytically effective amount of a mineral or organic sulfonic acid for a period sufficient to form 2-methyl-2-(methylsulfonyl) propionaldehyde 0-(methylcarbamoyl) oxime.
Reaction SMILES: [C:1]([O:5][C:6](=[O:11])[NH:7][CH:8]1[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.F[B-](F)(F)F.[N:23]#[O+:24]>C(#N)C>[C:1]([O:5][C:6](=[O:11])[N:7]([N:23]=[O:24])[CH:8]1[CH2:9][CH2:10]1)([CH3:4])([CH3:2])[CH3:3]
Reactant: N#[O+]
Reactant: CC(C)(C)OC(=O)NC1CC1
Agent: F[B-](F)(F)F
Solvent: CC#N
Solvent: c1ccncc1
Product: CC(C)(C)OC(=O)N(N=O)C1CC1
Temperature: 0 °C
Reaction time: 2.5 h
Yield: 26.4 %

Procedure:
A solution of cyclopropyl-carbamic acid tert-butyl ester (4.8 g, 30.5 mmol) and pyridine (5.9 mL, 73 mmol) in acetonitrile (75 mL) was cooled to approximately −25° C. in a carbon tetrachloride/dry ice bath. Nitrosonium tetrafluoroborate (4.7 g, 40.2 mmol) was added over a period of 20 min. The cooling bath was removed and the reaction mixture was stirred in an ice-bath at 0° C. for 2.5 h. Water (100 mL) and ethyl acetate (500 mL) were added and the organic layer was washed with water (100 mL), 2 M aqueous HCl (50 mL) and brine (100 mL), dried (magnesium sulfate), filtered, evaporated, and purified in two batches using an ISCO 120 g column, eluting with 10-30% ethyl acetate, to give N-nitroso-N-cyclopropyl-carbamic acid tert-butyl ester (1.5 g, 26%) as a yellow oil.
Reaction SMILES: [C:1]([O:5][OH:6])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+].[C:9](Cl)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.Cl>O>[C:9]([O:6][O:5][C:1]([CH3:4])([CH3:3])[CH3:2])(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CC(C)(C)OO
Reactant: O=C(Cl)c1ccccc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CC(C)(C)OOC(=O)c1ccccc1
Yield: 95.3 %

Procedure:
Before the start of the reaction, the loop reactor is filled with a solution of 19.6% by weight of tert-butyl hydroperoxide and 9.0% by weight of sodium hydroxide. Initially 18.4 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 11.8 kg/h of a solution of 50% by weight of sodium hydroxide in water, 35.2 kg/h of water and 18.0 kg/h of benzoyl chloride are then fed to the loop reactor. Cooling with cooling water keeps the internal temperature at 12° C. in the loop reactor and at 11° C. in the stirred cell reactor. The partial neutralization is effected with 2.2 kg/h of 31% by weight hydrochloric acid with addition of 6.0 kg/h of water at a temperature of 16° C. The organic phase is extracted with 17.2 kg/h of a 15% by weight aqueous solution of sodium hydroxide. This affords 18.4 kg/h of aqueous extract comprising 6.3% by weight of tert-butyl hydroperoxide and 14.1% by weight of sodium hydroxide, which are feeded into the loop reactor. From the time at which aqueous extract is recycled into the loop reactor, the metered addition of the feedstocks is changed to 16.8 kg/h of a solution of 70% by weight of tert-butyl hydroperoxide in water, 6.6 kg/h of a solution of 50% by weight of sodium hydroxide in water and 23.0 kg/h of water. After the extraction, the organic phase is washed with 36 kg/h of a solution of 1% by weight of sodium sulphite and 0.4% by weight of sulphuric acid, and dried by stripping at 35° C. and 43 mbar. 23.8 kg/h of tert-butyl peroxybenzoate with a purity of 99.7% are obtained (95.3% yield based on benzoyl chloride).
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=[O:5])[C:3]2=[CH:7][CH:8]=[CH:9][CH:10]=[C:2]12.[N:12]1([CH2:17][CH2:18][CH2:19][NH2:20])[CH:16]=[CH:15][N:14]=[CH:13]1.FC1C=CC=C2C(OC(=O)C=12)=O.ClC1C=C2C(=O)OC(=O)C2=CC=1Cl.CC1C=C2C(=O)OC(=O)C2=CC=1>C(Cl)Cl>[N:12]1([CH2:17][CH2:18][CH2:19][NH:20][C:4](=[O:5])[C:3]2[C:2](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:1]([OH:6])=[O:11])[CH:16]=[CH:15][N:14]=[CH:13]1
Reactant: O=C1OC(=O)c2ccccc21
Reactant: NCCCn1ccnc1
Agent: Cc1ccc2c(c1)C(=O)OC2=O
Agent: O=C1OC(=O)c2c(F)cccc21
Agent: O=C1OC(=O)c2cc(Cl)c(Cl)cc21
Solvent: ClCCl
Product: O=C(O)c1ccccc1C(=O)NCCCn1ccnc1

Procedure:
A mixture of 0.01 mole of phthalic anhydride, 0.01 mole of 3-(1H-imidazol-1-yl)propanamine and 30 ml. of methylene chloride was stirred at room temperature for 3 hours and concentrated. The residue was recrystallized from ethanol whereby the desired product, m.p. 160°-162° C., was obtained. By substituting 3-fluorophthalic anhydride, 4,5-dichlorophthalic anhydride, and 4-methylphthalic anhydride for the phthalic anhydride of this example, the compounds set forth in Table XX below were obtained.
Reaction SMILES: [N:1]1([C:6]2[CH:11]=[C:10]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:9]=[C:8]([CH:22]=[CH2:23])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[N+](=[CH2:26])=[N-]>C(OCC)C.C(O)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH:22]1([C:8]2[CH:9]=[C:10]([S:12]([C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)(=[O:14])=[O:13])[CH:11]=[C:6]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[N:7]=2)[CH2:26][CH2:23]1
Reactant: C=[N+]=[N-]
Reactant: C=Cc1cc(S(=O)(=O)c2ccc(N)cc2)cc(N2CCCC2)n1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Solvent: CCOCC
Solvent: CC(=O)O
Product: Nc1ccc(S(=O)(=O)c2cc(C3CC3)nc(N3CCCC3)c2)cc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 87 %

Procedure:
0.165 g (0.0005 Mol) 4-(2-Pyrrolidin-1-yl-6-vinyl-pyridine-4-sulfonyl)-phenylamine were dissolved in ethyl ether (100 ml) and cooled to 0° C. A solution of diazomethane in ethyl ether (30 ml) was carefully added. Upon addition of a catalytic amount of Pd(OAc)2 gas evolution started. The reaction mixture was allowed to warm to ambient temperature and stirred for 30 min. After addition of a few drops of acetic acid the solvent was evaporated and the residue chromatographed on SiO2 with ethyl acetate hexane 1:2. It was obtained 0.149 g (87%) of 4-(2-cyclopropyl-6-pyrrolidin-1-yl-pyridine-4-sulfonyl)-phenylamine as bright yellow cristals; mp.: 216-218° C.
Reaction SMILES: C1(N=C=NC2CCCCC2)CCCCC1.[CH2:16]([O:18][C:19]([C:21]1[CH:29]=[CH:28][C:24]([C:25]([OH:27])=O)=[CH:23][CH:22]=1)=[O:20])[CH3:17].[C:30]([CH:32]1[CH2:34][NH:33]1)#[N:31]>C(OCC)C>[CH2:16]([O:18][C:19]([C:21]1[CH:22]=[CH:23][C:24]([C:25]([N:33]2[CH2:34][CH:32]2[C:30]#[N:31])=[O:27])=[CH:28][CH:29]=1)=[O:20])[CH3:17]
Reactant: N#CC1CN1
Reactant: CCOC(=O)c1ccc(C(=O)O)cc1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Solvent: CCOCC
Product: CCOC(=O)c1ccc(C(=O)N2CC2C#N)cc1
Reaction time: 1 h

Procedure:
The same compound is obtained when a solution of 1.1 g. dicyclohexylcarbodiimide in 5 ml. diethyl ether is added at 0° C. to a mixture of 0.97 g. p-ethoxycarbonylbenzoic acid and 0.34 g. 2-cyanoaziridine in 15 ml. diethyl ether, stirred for 2 hours at this temperature and then for 1 hour at ambient temperature, the precipitated dicyclohexylurea is filtered off with suction (1.13 g.), the filtrate evaporated and the evaporation residue is triturated with about 3 ml. diethyl ether. The yield is 0.66 g.; m.p. 92°-94° C.
Reaction SMILES: O.[CH3:2][O:3][C:4]1[CH:5]=[CH:6][C:7]([N+:11]([O-:13])=[O:12])=[C:8]([CH3:10])[CH:9]=1.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:32]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:32][CH2:10][C:8]1[CH:9]=[C:4]([O:3][CH3:2])[CH:5]=[CH:6][C:7]=1[N+:11]([O-:13])=[O:12]
Reactant: COc1ccc([N+](=O)[O-])c(C)c1
Reactant: O=C1CCC(=O)N1Br
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Solvent: O
Product: COc1ccc([N+](=O)[O-])c(CBr)c1
Temperature: 25 °C
Yield: 46.6 %

Procedure:
The reaction apparatus consisted of a 50-mL single-necked round-bottom flask equipped with a water-jacketed condensor, magnetic stirrer, and an argon-filled balloon. A solution of 5-methoxy-2-nitrotoluene (0.25 g, 1.50 mmol), carbon tetrachloride (25 mL), a catalytic amount of benzoyl peroxide (25 mg, 0.83 mmol), and N-bromosuccinimide (0.32 g, 1.8 mmol) were added to the reaction flask. The mixture was refluxed and irradiated under a 90-watt lamp (GE watt-miser light bulb, 130 V, 1000 hrs) for 5 h and then cooled to room temperature. The precipitated succinimide was removed by gravity filtration and the filtrate was extracted with sodium metabisulfite (28 M, 1×50 mL) and water (1×50 mL). The organic layer was separated, dried over sodium sulfate, filtered and then evaporated to afford a crude oil (382 mg, 105%). The crude product was chromatographed on silica gel (hexane/EtOAc=9:1) to give the product as yellow crystals (172 mg, 47%): m.p. 64–65° C.