Oxidation of various secondary amines to imines with N-tert-butylphenylsulfinimidoyl chloride

Article abstract of DOI:10.1246/cl.2001.390

Various secondary amines were smoothly oxidized to the corresponding imines at -78 °C by using N-tert-butylphenylsulfinimidoyl chloride and DBU.

Full text of DOI:10.1246/cl.2001.390

390
Chemistry Letters 2001
Oxidation of Various Secondary Amines to Imines
with N-tert-Butylphenylsulfinimidoyl Chloride
Teruaki Mukaiyama,* Asahi Kawana, Yoshio Fukuda, and Jun-ichi Matsuo
Department of Applied Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601
(Received January 29, 2001; CL-010083)
Various secondary amines were smoothly oxidized to the
corresponding imines at –78 °C by using N-tert-butylphenyl-
sulfinimidoyl chloride and DBU.
of non-conjugated imines were determined after hydrolysis into
the corresponding aldehydes since the non-conjugated imines
were easily hydrolyzed in aqueous work-up procedures. It was
interesting to note that the oxidations of N-pentylaniline and N-
(cyclohexylmethyl)aniline proceeded smoothly even at –78 °C
in contrast to the cases of simple primary alcohols which were
not oxidized completely with 1 and DBU at –78 °C.11a
Mild and efficient oxidation of amines to the corresponding
imines1 would provide a new synthetic possibility in organic
synthesis because the formed imines are susceptible to nucle-
ophilic additions which enable the introduction of a new sub-
stituent at the β-position of the amine functionality. In recent
years, several trials of the amine-oxidation forming imines were
reported in the field of natural products synthesis.2 A variety of
oxidants that realize this transformation have been developed to
date: e.g. hypervalent iodine reagents,3,2a phenylselenic anhy-
dride,4 manganese dioxide,5 and so on.6 Oxidation of amines
was also carried out by using a catalytic amount of ruthenium
The present oxidation reaction was applicable not only to
N-substituted anilines but also to various N-substituted second-
ary amines (Entries 10–15). However, the oxidation of N-ben-
zyl(triphenylmethyl)amine did not proceed at all probably due to
the steric hindrance of triphenylmethyl group (Entry 12). In the
cases of unsymmetrical secondary amines, two different imines
are expected to form by the oxidation reaction. It was found that
benzylic part was selectively oxidized in the oxidation of N-
(cyclohexyl)benzylamine, and N-(benzilidene)cyclohexylamine
was detected in 94% yield (Entry 13). This result can be
explained by the unsuccessful formation of ketimines in the
present oxidation; ketimines were hardly detected in the oxida-
tion of N-cyclohexylaniline or N-(diphenylmethyl)aniline even
at elevated temperatures. On the other hand, the oxidation of N-
hexylbenzylamine took place on the either two alkyl groups to
form two kinds of aldimines. Of these two products, the oxida-
tion of benzylic part was moderately preferred (Entry 14). It
was notable that the regioselectivity was also influenced by an
electronic factor as exemplified in the oxidation of N-(2-
methoxybenzyl)benzylamine, followed by one-pot hydrolysis
giving benzaldehyde and 2-methoxybenzaldehyde in 32% and
53% yields, respectively (Entry 15). This result suggested that
the electron-rich alkyl group facilitated the dehydrogenation to
imines.
The oxidation of cyclic secondary amines such as indoline
and 1,2,3,4-tetrahydroisoquinoline gave indole and 3,4-dihy-
droisoquinoline, respectively, in moderate yields (Entries 16
and 17). Indoline was oxidized to indole in a better yield by
using 1.2 equivalents of 1 and DBU. Additionally, the present
oxidation method was applied to oxidative deamination of pri-
mary amines. As a preliminary experiment (Entry 18), ben-
zophenone was obtained in 52% yield on treating benzhydryl-
amine with the combination of 1 and DBU, followed by acid
hydrolysis.
9
catalysts,7,3c cobalt-Shiff base complex,8 or NiSO4 in the pres-
ence of an appropriate co-oxidant. Most of these known meth-
ods have only been applied to oxidation of benzylic and allylic
amines, which afford conjugated imines at room temperature or
above, and a limited number of examples were reported for oxi-
dation of aliphatic amines to non-conjugated imines. Therefore,
a new amine-oxidizing reagent that has wider applicability and
wider functional tolerance is now strongly desired.
Overton et al. reported that the oxidation of secondary
amines by Swern oxidation method (DMSO-oxalyl chloride)
yielded the corresponding imines along with considerable
amounts of methylthiomethylamines as by-products.10a In the
present study, oxidation of amines to the corresponding imines
was examined by using a combination of N-tert-butylphenyl-
sulfinimidoyl chloride (1) and DBU, which was previously
reported to be the effective combination of reagents for oxida-
tion of alcohols into carbonyl compounds.11
In the first place, oxidation of N-benzylaniline (2a) to N-
benzylideneaniline (3a) was tried with the above-mentioned
reagents. Expectedly, 2a was oxidized instantaneously even at
–78 °C by using two equivalents of 1 and DBU, and 3a was
detected by 1H NMR in 92% yield.12 The formation of 3a was
also confirmed by one-pot hydrolysis of 3a with 1M HCl solu-
tion to afford benzaldehyde in 94% yield (Table 1, entry 1).
The formed 3a was methylated in a one-pot manner to afford N-
(1-phenylethyl)aniline in 77% yield by adding three equivalents
of methyllithium after the oxidation in THF. Further, the oxi-
dations of N-benzyl-4-methoxyaniline (2c) and N-benzyl-4-flu-
oroaniline (2b) were examined in order to investigate the effect
of aniline ring substituents. However, no differences were
observed at all because the oxidations proceeded very quickly
at –78 °C in both cases (Entries 2 and 3).
It should be noted that various secondary amines were effi-
ciently oxidized to the corresponding imines under mild condi-
tions (at –78 °C) by using the combination of 1 and DBU.
Further studies on oxidative deamination of primary amines
into the corresponding carbonyl compounds by using 1 are now
under way.
Typical experimental procedure (Table 1, entry 6) is as fol-
lows: to a stirred solution of N-cinnamylaniline (110 mg, 0.53
mmol) and DBU (146 mg, 0.96 mmol) in CH2Cl2 (3 mL) was
added a solution of 1 (206 mg, 0.96 mmol) in CH2Cl2 (1 mL) at
In addition to N-benzylideneamines, other conjugated
imines and non-conjugated imines were also successfully
formed at –78 °C by the present oxidation (Entries 4–9). Yields
Copyright © 2001 The Chemical Society of Japan

Chemistry Letters 2001
391
The present work was partially supported by Grant-in-Aids
for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and Notes
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12 The isolated yields were not shown here since the formed
imines were partially decomposed during the isolation pro-
cedures such as silica gel or alumina column chromatogra-
phy.
–78 °C. After the reaction mixture was stirred at the same tem-
perature for 30 min, the reaction was quenched with saturated
aqueous NaHCO3 solution and the resulting mixture was
extracted with CH2Cl2. The combined organic extracts were
dried with anhydrous Na2SO4, filtrated, and concentrated to
give a crude product. The formation of N-cinnamylideneaniline
was confirmed by 1H NMR spectrum by comparing it to that of
an authentic sample, and its yield (0.51 mmol, 98%)12 was
1
determined by H NMR spectrum using triphenylmethane (128
mg, 0.53 mmol) as an internal standard.