4-Toluenesulfonyl chloride → N-(2,5-difluorophenyl)-4-methylbenzenesulfonamide

HRID 1030966Notes

Reaction equation

HRID 1030966 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][C:3]=1[NH2:4].[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([S:17](Cl)(=[O:19])=[O:18])=[CH:13][CH:12]=1>N1C=CC=CC=1>[CH3:10][C:11]1[CH:16]=[CH:15][C:14]([S:17]([NH:4][C:3]2[CH:5]=[C:6]([F:9])[CH:7]=[CH:8][C:2]=2[F:1])(=[O:19])=[O:18])=[CH:13][CH:12]=1

Participants

4

Reactant 2

HCID 73974-Toluenesulfonyl chlorideHCID 677752,5-Difluoroaniline

Product 1

HCID 8500594N-(2,5-difluorophenyl)-4-methylbenzenesulfonamide

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Following Intermediate Method 1, a substituted aniline, for example 2,5-difluoroaniline, may be reacted with 4-methylphenylsulfonyl chloride in pyridine to form N-(4-methylphenylsulfonyl)-2,5-difluoroaniline, (V). Nitration of (V) with sodium nitrite in nitric acid, acetic acid and water produces N-(4-methylphenylsulfonyl)-2,5-difluoro-4-nitroaniline, (VI). The reaction of (VI) with aqueous sulfuric acid yields 2,5-difluoro-4-nitroaniline, (VII). Subsequent reaction of (VII) with acetic anhydride and a small amount of dimethylaminopyridine (DMAP) in methylene chloride produces N-(2,5-difluoro-4-nitrophenyl)-acetamide (VIII). Treatment of (VIII) with a borane/dimethyl sulfide complex in tetrahydrofuran yields N-ethyl-2,5-difluoro-4-nitroaniline, (IX). Repeating the previous two steps, the reaction of (IX) first with acetic anhydride (to produce N-(2,5-difluoro-4-nitrophenyl)-acetamide, (X)) followed by treatment with a borane/dimethyl sulfide complex yields N,N-diethyl-2,5-difluoro-4-nitroaniline, (XI). Hydrogenation of (XI) with platinum oxide in ethanol produces the desired 2,5-difluoro-4-diethylaminoaniline, (XII). ##STR28##

Sources & evidence

ORD record
ord-677bd1eb2b494798bb03cda5589a0c0c
Source dataset
uspto-grants-1992_04
Patent number
US05108486

Reaction notes

Loading…