Amination of arenes with N,N-dimethyl-2-imidazolidinone O-methoxyacetyloxime

Article abstract of DOI:10.1246/cl.2003.548

Treatment of nucleophilic arenes with N,N-dimethyl-2imidazolidinone O-methoxyacetyloxime and SnCl₄ produced the corresponding N-arylimines, which were converted to anilines by hydrolysis with CsOH and to N-methylanilines by LiAlH₄ reduction.

Full text of DOI:10.1246/cl.2003.548

548
Chemistry Letters Vol.32, No.6 (2003)
Amination of Arenes with N,N-Dimethyl-2-imidazolidinone O-Methoxyacetyloxime
Nicolas Baldovini, Mitsuru Kitamura, and Koichi Narasakaꢀ
Department of Chemistry, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033
(Received March 31, 2003; CL-030271)
Table 1. Amination of 1,3-dimethoxybenzene 1a with 2-4a
Treatment of nucleophilic arenes with N,N-dimethyl-2-
imidazolidinone O-methoxyacetyloxime and SnCl4 produced
the corresponding N-arylimines, which were converted to ani-
lines by hydrolysis with CsOH and to N-methylanilines by
LiAlH4 reduction.
OMe
OMe
Y
Y
N
XO
Y
SnCl4
rt
+
N
Y
MeO
MeO
5 : Y=O
6 : Y=O,NMe
7a : Y=NMe
1a
2-4
Me
XO
N
TsO
TsO
Direct amination of arenes has been considered as a
straightforward method for the synthesis of aniline derivatives.1
In the course of our study on the utilization of oxime deriva-
tives as electrophilic amination reagents,2 it was found that in
the presence of Lewis acids, cyclic O-sulfonyl- or O-acyloximes
could be used for the amination of nucleophilic arenes. This
process involves the formation of imines from the oximes and
arenes and the successive hydrolysis leading to the correspond-
ing anilines (Figure 1).
O
O
N
N
N
O
N
N
2
3
4
Me
Me
OMe
O
O
O
O
OMe
OMe
O
X = Ts
4a
4b
4c
4d
4e
Entry
Oxime
1a/equiv.
Time
Yield/%
b
1
2
3
2
3
10
10
10
10
1
1
1
1
1
24 h
24 h
24 h
1.5 h
7min
5
—
6c
<10
81d
86
87d
86
81
5
<8
4a
4b
4b
4b
4c
4d
4e
7ac
7ac
7ac
7ac
7ac
7ac
7ac
4
XO
Y
Y
5e,f
6e
7e
8e
9e
N
hydrolysis
N
NH2
15 min
15 min
15 min
15 min
Y
X= sulfonyl, acyl...
Y= NH, O...
R
Y
R
R
Figure 1. Amination of arenes with oxime derivatives.
a) 2-4 : SnCl4 = 1 : 2.5. b) Imine 5 was directly hydrolysed
without isolation (HCl, MeOH, reflux 1.5 h) to give 2,4-di-
methoxyaniline in 13%. c) Imines 6 and 7a were not hydro-
First, the amination of 1,3-dimethoxybenzene (1a) was in-
vestigated with several O-sulfonyloxime derivatives 2,3,4a2e
and SnCl4 as Lewis acid (Table 1, Entries 1–3). As expected
from the properties of the oximes of ureas and carbonates, we
hoped that these reagents would not suffer from unwanted side
reactions such as Beckmann rearrangement and Neber reaction.
O-sulfonyloxime of cyclic carbonate 2 led to a complex mixture
in which only a small amount of 2,4-dimethoxyaniline was
identified after acidic hydrolysis (Entry 1). Imine 6 was formed
in a poor yield from 1,3-oxazolidinone O-sulfonyloxime 3 and
could not be hydrolyzed by the subsequent acidic treatment (En-
try 2). O-sulfonyloxime of cyclic urea 4a proved to be more in-
teresting. Its corresponding imine 7a was formed in 81% yield,
but was also resistant to acidic hydrolysis (Entry 3). We inves-
tigated then more closely the properties of the N,N-dimethyl-2-
imidazolidinone oxime fragment by replacing the tosyl group of
4a with another type of leaving group. Our first experiments
with the methoxyacetyl group were very encouraging as 4b re-
acted exothermically to afford the expected N-arylimine 7a in
high yield (Entry 4), and even with an equimolar amount of
1a in dichloromethane at 0 ꢁC, the reaction was rapidly com-
pleted, giving a similar yield of 7a (Entry 5).
1
lysed in acidic conditions. d) Yield was determined by H
NMR spectroscopy with anthracene as an internal standard.
e) Reaction was carried out in CH2Cl2 (0.5 M). f) Reaction
was carried out at 0 ꢁC.
(Entry 6), and compound 4c which can be seen as a conforma-
tionally restricted analogue of 4b afforded a slightly lower yield
of 7a (Entry 7). The O-b-methoxypropionyl oxime 4d led only
to 5% of the desired product (Entry 8), together with unreacted
dimethoxybenzene, and the o-methoxybenzoyl derivative 4e af-
forded also a low yield of 7a (Entry 9). The O-tosyloxime 4a
was also included in this study, and while a good yield of imine
was obtained with dimethoxybenzene (1a) used as a solvent in
24 h (Entry 3), no product formation was detected when it was
treated with a stoichiometric amount of 1a in CH2Cl2 for a short
time.
Interestingly, only SnCl4 promoted the reaction of 4b with
dimethoxybenzene (1a). All our experiments with another Le-
wis acid or Lewis acids combination resulted in poor yields
of imine 7a or surprisingly, no imine formation at all with most
of the conventional Lewis acids such as TiCl4, EtAlCl2, ZnCl2,
and MgBr2. The reaction described in this work involves prob-
ably a nucleophilic attack of the arene on the nitrogen atom of
the oxime.4 Tin chloride would assist the cleavage of the N-O
bond by coordination of Sn4þ with the oxygen atom, in analogy
This result prompted us to explore the reactivity of other
methoxyacyl analogues. Compounds 4b–e3 were treated at
room temperature with an equimolar amount of 1a and 2.5 mo-
lar amounts of SnCl4 for 15 min (Entries 6–9). As expected
from the precedent results, 4b gave a 86% yield of imine 7a
Copyright ꢀ 2003 The Chemical Society of Japan

Chemistry Letters Vol.32, No.6 (2003)
Table 2. Synthesis of anilines and N-methylanilines by the reaction of 4b with aromatic compoundsa
549
•
CsOH H2O
Me
N
8
MeO
ethylene glycol
160 °C, 4 h.
Me
N
N
O
N
SnCl4
rt
7 : X =
8 : X = NH2
N
O
ArH
+
7
ArX
Me
N
1
LiAlH4
Me
9
9 : X = NHCH3
4b
THF, reflux, 24 h.
Yield from ArH/% [ratio o- : p-]
Entry
7b
8c
9c
ArH
(equiv.)
ArX
MeO
OMe
MeO
OMe
88d
96d
53
12
62
94e
1
2
(1)
(1)
1a
X
OMe
MeO
OMe
MeO
OMe
1b
X
OMe
OMe
OMe
OMe
p-
OEt
3
4
85 [54:46]
87 [52:48]
80 [52:48]
86 [51:49]
75 [54:46]
77 [57:43]
(10)
(10)
(10)
1c
o-
X
X
X
OEt
1d
OEt
X
p-
OMe
o-
OMe
OMe
X
5
61 [23:77]
58 [22:78]
50 [6:94]
1e
X
p-
o-
1
a) 4b : SnCl4 = 1 : 2.5. b) Yield was determined by H NMR spectroscopy with anthracene as an internal
standard. c) Isolated yield. d) Reaction was carried out in CH2Cl2 (0.5 M). e) LiAlH4 reduction conducted at
rt.
with the Beckmann rearrangement. Calculation studies showed
that the rate-determining step for the Beckmann rearrangement
was the 1,2-proton shift from the N-protonated oxime to the O-
protonated form, which can be strongly assisted by solvent
participation.5 The highest reactivity of 4b may thus be ex-
plained by a similar 1,2 shift of tin cation assisted by the parti-
cipation of the methoxy group of the methoxyacetyl substituent.
Finally, the transformation of imine 7a into dimethoxyani-
line 8a was studied. While the hydrolysis of this type of imines
did not proceed by acid treatment, a careful investigation
showed that the best results are obtained by treatment with
CsOHꢂH2O in ethylene glycol at 160 ꢁC. Alternatively, the re-
duction of 7a with LiAlH4 gives access to the N-
methyldimethoxyaniline.2e
The present method was then applied to the amination of
various aromatic substrates as listed in Table 2. The most elec-
tron-rich arenes 1a and 1b reacted rapidly with an equimolar
amount of 4b and afforded excellent yields of the corresponding
imines, while less nucleophilic arenes such as 1c–1e had to be
used in 10 molar excess and required a longer reaction time.
The hydrolysis of 7 into aniline 8 was nearly quantitative for
the monoalkoxyarylimines (Entries 3–5) but led only to a
53% overall yield with the dimethoxyarylimine and 12% for
the trimethoxyarylimine sustaining oxidation of the correspond-
ing anilines (Entries 1 and 2). Conversely, most imines were ef-
ficiently converted to N-methylanilines 9 and a 94% overall
yield was achieved for the methylamination of trimethoxyben-
zene 1b. However, the ortho-isomer of the imine obtained from
1e could not be reduced completely (Entry 5).
arenes, giving anilines or N-methylanilines after subsequent ba-
sic hydrolysis or LiAlH4 reduction.
This work was supported by a “JSPS Postdoctoral Fellow-
ship for Foreign Researchers” from the Japan Society for the
Promotion of Science and by a Grant-in-Aid for Scientific Re-
search on Priority Areas (A) “Exploitation of Multi-Element
Cyclic Molecules” from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
References and Notes
1
F. Minisci, Synthesis, 1973, 1; G. A. Olah and T. D. Ernst, J.
Org. Chem., 54, 1203 (1989); H. Takeuchi, T. Adachi, and
H. Nishiguchi, J. Chem. Soc., Chem. Commun., 1991, 1524;
S. Seko and N. Kawamura, J. Org. Chem., 62, 442 (1996).
a) H. Tsutsui, Y. Hayashi, and K. Narasaka, Chem. Lett.,
1997, 317. b) K. Uchiyama, M. Yoshida, Y. Hayashi, and
K. Narasaka, Chem. Lett., 1998, 607. c) H. Tsutsui, T.
Ichikawa, and K. Narasaka, Bull. Chem. Soc. Jpn., 72,
1869 (1999). d) M. Yoshida, K. Uchiyama, and K.
Narasaka, Heterocycles, 52, 681 (2000). e) M. Kitamura,
S. Chiba, and K. Narasaka, Bull. Chem. Soc. Jpn., 76,
1063 (2003).
2
3
4b–e were obtained by conventional esterification of N,N-
dimethyl-2-imidazolidinone oxime with the corresponding
acid chlorides in the presence of triethylamine or with tetra-
hydro-2-furoic acid, DCC and DMAP in the case of 4c.
S. Mori, K. Uchiyama, Y. Hayashi, K. Narasaka, and E.
Nakamura, Chem. Lett., 1998, 111.
4
5
As described above, O-acyloxime derivatives such as 4b
can be used as electrophilic aminating reagents of nucleophilic
M. T. Nguyen, G. Raspoet, and L. G. Vanquickenborne, J.
Am. Chem. Soc., 119, 2552 (1997).
Published on the web (Advance View) May 27, 2003; DOI 10.1246/cl.2003.548