JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2007; 20: 671–676
Published online 30 July 2007 in Wiley InterScience
On the mechanism of the N,N-dimethyl amination
of Grignard reagents: a kinetic study
y
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*
Ender Erdik and Selma Ates¸ Ulhu¨
Science Faculty, Ankara University, Bes¸evler, Ankara 06100, Turkey
Received 31 March 2007; revised 16 May 2007; accepted 22 May 2007
ABSTRACT: A direct kinetic study is reported for the electrophilic amination of substituted phenylmagnesium
bromides with N,N-dimethyl O-(mesitylenesulfonyl)hydroxylamine in THF. Rate data, Hammett relationship, and
activation entropy are consistent with a SN2 displacement involving the attack of carbanions to sp3N in the amination
reagent (AR). Copyright # 2007 John Wiley & Sons, Ltd.
KEYWORDS: Grignard reagents; aryl carbanions; electrophilic amination; C—N coupling; N,N-dimethyl
O-(mesitylenesulfonyl)hydroxylanine; Hammett plot; activation parameter
INTRODUCTION
are limited. Beak’s23–25 group provided evidence for a
polar SN2-like mechanism for the reactions of organo-
lithiums and a-lithionitriles with 1a and 1e. Ricci and
coworkers26 offered a similar mechanism for the amina-
tion of higher order lithium cuprates with 1c. Theoretical
calculations by Boche and Wagner,27 Armstrong, et al.,28
and McKee29 support a transition state for this
mechanism. We recently reported our work on the kinetic
studies of the amination of carbanions with ace-
tone O-(mesitylenesulfonyl)oxime (2a, R ¼ CH3, R1 ¼
C6H2(CH3)3-2,4,6)30 and with O-methyl hydroxylamine
(1a, R1 ¼ CH3).31 We investıgated substituent effects on
the amination rate of phenylmagnesium bromides,30,31
magnesium diphenylcuprates,31 and also CuCN catalyzed
phenylzinc chlorides30 and diphenylzincs31 by competi-
tive kinetic studies. Analyses of rate data via Hammett
treatment were explained by SN2 mechanism for Grignard
reagents and by nucleophilic oxidative addition mech-
anism for catalytic and stoichiometric cuprates. Although
linear Hammett plots supported the assumption of
first-order reaction in organometallic reagent in the
amination with these reagents, we have been exploring
reaction conditions to carry out a direct kinetic study for
the electrophilic amination.
Amines are one of the important class of compounds in
organic synthesis and also substructures of many natu-
rally occurring compounds and pharmaceuticals. For the
amine synthesis,1 nucleophilic amination strategy is
commonly in use, however transitıon metal catalyzed
C—N couplings between aryl halides and amines have
received special attention.2–4 Electrophilic amination
strategy is also a potentially valuable method for
nonsymmetric and symmetric synthesis of amines1,5–7
and a-amino carbonyl compounds (Scheme 1).8,9
A
number of electrophilic amination reagents (ARs), that is,
synthetic equivalents of ꢀNR2 synthon (1,2) have been
reported for C—N coupling with carbanions (Scheme 1).
Notably among these are: (i) sp3N type ARs (1).
O-Organyl hydroxylamines (1a),5–9 O-acylhydroxyla-
mines (1b),10–14 O-silylhydroxylamines (1c),5–9 O-sulfo-
nylhydroxylamines (1d),5–9,15 and O-phosphinylhydro-
xylamines (1e)5–9 react with carbanions directly.
(ii) sp2N type ARs (2). O-Sulfonyloximes (2a)16–18 form
imines, which are hydrolyzed to amines. Azides (2b),5–9
diazene dicarboxylates (2c),5–9 arene diazonium salts
(2d),19–21 and nitroarenes (2e)22 form intermediates
which require reductive work-up to produce amines.
Although synthetic potential of electrophilic amination
has been extensively studied, mechanistic investigations
In our recent work15 on the successful use of Grignard–
Barbier type amination with N,N-dimethyl derivative
of O-(mesitylenesulfonyl)hydroxylamine (1d, R1 ¼
C6H2 (CH3)3-2,4,6), we observed that amination takes
place in a homogeneous solution. This finding and our
continuing investigations into synthetic and mechanistic
aspects of electrophilic amination encouraged us to
perform an extensive kinetic investigation of the C—N
*Correspondence to: E. Erdik, Science Faculty, Ankara University,
Bes¸evler,Ankara 06100, Turkey.
yE-mail: erdik@science.ankara.edu.tr
Present Address: College of Liberal Arts and Sciences, Wayne State
University, Detroit, Michigan 48202, USA.
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 671–676