Section 21.8 Synthesis of Amines 895The major product of the Cope elimination, like that of the Hofmann elimination, is
the one obtained by removing a hydrogen from the -carbon bonded to the greater
number of hydrogens.
PROBLEM 11Does the Cope elimination have an alkene-like transition state or a carbanion-like transi-
tion state?PROBLEM 12Give the products that would be obtained by treating the following tertiary amines with hy-
drogen peroxide followed by heat:a. c.b. d.21.8 Synthesis of Amines
Because ammonia and amines are good nucleophiles, they readily undergo reac-
tions with alkyl halides. (X denotes a halogen.)
Although these reactions can be used to synthesize amines, the yields are poor be-
cause it is difficult to stop the reaction after a single alkylation since ammonia and pri-
mary, secondary, and tertiary amines have similar reactivities.
A much better way to prepare a primary amine is by means of a Gabriel synthesis
(Section 17.17). This reaction involves alkylating phthalimide and then hydrolyzing
the N-substituted phthalimide.
SN 2SN 2CH 3
CH 3NCH 3 NCH 2 CH 2 CH 3CH 3CH 3CH 3 CH 2 NCH 2 CHCH 3CH 3CH 3 NCH 2 CH 2 CH 3+
+CH 3O− OHCH 3 CH 2 NCH 2 CH 2 CH 3 CH 2 CH 2 NCH 2 CH 2 CH 3CH 3
∆bIn a Cope elimination, the hydrogen is
removed from the -carbon bonded to
the most hydrogens.BNH 3 RCH 2 RCH 2
a primary amineRCH 2 X RCH 2 XRCH 2 XRCH 2 XNH 3 NH 2 RCH 2 NH+
RCH 2RCH 2 RCH 2NH 2+RCH 2RCH 2RCH 2RCH 2RCH 2RCH 2 N NHRCH 2RCH 2RCH 2 N CH 2 R++ HX
a secondary amine+ HXa quaternary a tertiary amine
ammonium salt + HX