Aniline → N-(2-hydroxycycloheptyl)aniline
Reaction equation
[CH:1]12[O:8][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]2.[NH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>>[OH:8][CH:1]1[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[NH:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1Participants
Procedure
Reaction of the cycloheptene oxide IIIa with an aniline under conditions well known in the art gives the N-(2-hydroxycycloheptyl)-aniline IX which, when reacted with chlorosulfonic acid in a non-polar organic solvent, e.g., methylene chloride, at 20°-30° C., followed by heating with a selected C1 to C3 -monoalkylamine (aqueous) or ammonium hydroxide (aqueous) at 100°-150° C. for 40-55 hours at elevated pressure (2-10 atm.), gives the diamine VI. Reaction of diamine VI with 2,2,2-trichloroethyl chloroformate, or equivalent N-blocking compound, at 20°-30° C. for 1-5 hours proceeds in the presence of an acid scavenger, e.g., triethylamine, to give the 2-(N-blocked amino) compound XIV. Acylation of the N-blocked compound XIV with the selected acid anhydride, ##STR19## by heating at 90°-120° C. for 12 to 30 hours gives the N-blocked anilide XV. Deprotection of the 2-amino function of the 2-N-blocked anilide XV is then accomplished by reaction with an N-deblocking agent such as metal dust in acid, e.g., zinc in acetic acid, in a polar organic solvent, e.g., methanol, at 20°-100° C. for 2 to 6 hours. Work-up, isolation and purification procedures are those standard in the art of organic chemistry.
Sources & evidence
- ORD record
- ord-6be0df4c54e04d35b466303bd0d4f5d0
- Source dataset
- uspto-grants-1979_06
- Patent number
- US04159339
Reaction notes
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