An inexpensive and selective oxygenation of N-alkyl imines to oxaziridines

Article abstract of DOI:10.1055/s-2005-865219

A range of N-alkyl imines was oxidised to corresponding oxaziridines in a highly selective manner with sodium tungstate-30% H₂O₂ in acetonitrile under mild conditions.

Full text of DOI:10.1055/s-2005-865219

1176
LETTER
An Inexpensive and Selective Oxygenation of N-Alkyl Imines to Oxaziridines
Oxygenation of
N
-Alk
.
yl Imines toO
S
xaziridines hailaja, A. Manjula, B. Vittal Rao*
Organic Division II, Indian Institute of Chemical Technology, Hyderabad 500 007, India
E-mail: vittalrao@iict.res.in
Received 3 January 2005
Herein we report a highly effective oxidation of aldimines
Abstract: A range of N-alkyl imines was oxidised to corresponding
oxaziridines in a highly selective manner with sodium tungstate–
30% H2O2 in acetonitrile under mild conditions.
to the corresponding 2-alkyl-3-aryloxaziridines, in good
to high yields, employing the sodium tungstate–H2O2 sys-
tem (Scheme 1). We found that commercial H2O2 of mod-
erate concentration (ca. 30%) in combination with 10 mol
percent sodium tungstate was sufficient for oxidation us-
ing acetonitrile as the solvent.
Key words: imines, oxidation, oxaziridine, sodium tungstate, per-
oxide
Since the first reports by Krimm,1 Emmons2 and Horner
and Jurgens,3 oxaziridines have occupied a unique posi-
tion in organic synthesis. They are useful aprotic
oxidising4 agents especially when acid sensitive groups
are present in the system. A unique feature of the oxaziri-
dine system is its unusual reactivity due to the strained
three-membered ring and a weak N-O bond coupled with
the low basicity of the ring nitrogen and these characteris-
tics have led them being used as both nitrogen as well as
oxygen transfer reagents in synthesis.5 Some N-alkyl ox-
aziridines also possess a configurationally stable nitrogen
at room temperature with inversion barriers in the range
24–30 kcals/mol6 which results in optical activity due to
nitrogen centre. These systems have been extensively
used in asymmetric synthesis.7 Recent reports have indi-
cated that oxaziridines have antifungal properties thus in-
dicating their biological potential.8 Therefore, the
efficient synthesis of the oxaziridine system continues to
be a significant goal and considerable challenge in organic
synthesis.
R2
O
H2O2, Na2WO4·2H2O
R2
N
MeCN, r.t.
N
H
R1
R1
H
Scheme 1
A range of aldimines was subjected to oxidation using so-
dium tungstate–H2O2 (30%) in acetonitrile at room tem-
perature.16 The results are presented in Table 1. The effect
of electron-donating and -withdrawing substituents on the
phenyl ring attached to the C-atom of the aldimine has
also been investigated and was found to have an effect on
the rate of the oxidation. Reaction proceeds at a faster rate
with electron-withdrawing groups present on the phenyl
ring. Another notable observation is that the oxidation
produces the best results when carried out in acetonitrile.
While no change was observed in chlorinated solvents, in
solvents such as MeOH and acetone decomposition of the
imine predominates.
The most useful synthetic route to the oxaziridines has
been via the oxidation of imines by suitable oxidising
agents. Several reagents have been employed starting
from classical peracids such as m-CPBA,9 Ac2O/H2O2,10
urea/H2O2,11 H2O2/nitriles,12 buffered oxone,13 t-amyl-
hydroperoxide14 and molecular oxygen in the presence of
transition metals.15 Since this oxidation is sensitive to a
variety of factors, most of the reagents reported have lim-
itations. For example, in methods involving peracids or
the in situ generation of peracids, the harsh reaction con-
ditions result in decomposition of the product formed and
hydrolysis of the imine. In the case of the H2O2/benzo-
nitrile system, yields are poor due to the biphasic nature of
the reaction and the formation of side products similar to
those observed in the urea/H2O2 system.
All the oxaziridines are formed as single isomers, as is ev-
ident from Table 1. The E- and the Z-isomers of substitut-
ed oxaziridines are known to give different chemical
shifts for the lone C-H in the oxaziridine ring: in the E-iso-
mer around d = 4.6 ppm and in the Z-isomer around d =
5.2 ppm.12 The chemical shifts observed fall in a range of
d = 4.4–4.8 ppm indicative of the formation of a single E-
isomer.
Both R-(+)- and S-(–)-1-phenethyl amine and the race-
mate were reacted with 2-methyl benzaldehyde to furnish
the corresponding chiral imines. The sodium tungstate–
H2O2 oxidation of the imines yielded the corresponding
oxaziridines (entry 17, 18 and 19 in Table 1). The proton
NMR spectrum showed two signals (singlets) for the lone
proton of the 3-membered ring around d = 4.7 ppm, sepa-
rated by less than 0.1 ppm. It is a well-established fact that
oxidation of chiral imines with m-CPBA gives four sig-
nals for the lone proton of the oxaziridine ring. Two sin-
glets at d = 4.3 ppm correspond to the E-diastereoisomers
and another two singlets at d = 5.1 ppm of the Z-diastereo-
mers.
SYNLETT 2005, No. 7, pp 1176–1178
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Advanced online publication: 14.04.2005
DOI: 10.1055/s-2005-865219; Art ID: D00305ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Oxygenation of N-Alkyl Imines to Oxaziridines
1177
Table 1 Oxidation of Aldimines Using Sodium Tungstate–H2O2 (30%) in MeCN at Room Temperature
Entry
1
Aldimine
Oxaziridine
Yield (%)
96
dH (ppm)
Time (h)
4.64
4.5
O
H
H
N
N
2
3
66
72
4.37
4.37
4.5
H
O
H
(CH2)5CH3
(CH2)5CH3
N
N
Cl
F
Cl
F
4.5
H
O
H
N
N
4
5
6
7
70
70
95
60
4.40
4.42
4.80
5.07
4
4
5
3
H
O
H
N
N
N
(CH2)5CH3
N
N
N
(CH2)5CH3
H
O
O
H
H
H
O
N
H
H
N
F
CF3
F
CF3
N
8
9
60
50
4.46
4.77
3
3
H
O
N
H
N
N
H
O
N
H
N
N
Cl
N
Cl
(CH2)3CH3
10
65
4.75
3
O
N
H
H
(CH2)3CH3
N
F
CF3
N
F
CF3
11
12
60
60
4.41
4.48
4.5
1
H
O
H
N
(CH2)3CH3
(CH2)3CH3
H
H
O
N
N
O2N
O2N
13
14
15
62
73
62
4.51
4.66
4.67
2
3
4
H
O
N
H
N
N
O2N
O2N
O2N
O2N
H
H
O
N
O
H
H
N
N
Synlett 2005, No. 7, 1176–1178 © Thieme Stuttgart · New York

1178
M. Shailaja et al.
LETTER
Table 1 Oxidation of Aldimines Using Sodium Tungstate–H2O2 (30%) in MeCN at Room Temperature (continued)
Entry
16
Aldimine
Oxaziridine
Yield (%)
60
dH (ppm)
Time (h)
15
–
C=N
H
N
H3CO
H3CO
CHO
H3CO
30
70
17
18
4.82 (33)
4.89 (66)
4
4
H
O
O
H
Ph
H
Ph
H
CH3
N
N
N
CH3
R–
68
74
4.70 (30)
4.75 (70)
H
H
H
Ph
H
CH3
Ph
H
CH3
N
S–
19
4.72 (30)
4.78 (70)
4
O
N
H
Ph
H
CH3
Ph
H
CH3
N
DL
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However, with the hydrogen peroxide–benzonitrile sys-
tem the oxidation of chiral imines resulted in only two sin-
glets at d = 4.5 ppm. They were assigned as the E-
diastereoisomers as they had less than 0.1 ppm difference
in their chemical shifts. A very similar difference in the
chemical shifts found with our oxidation system indicates
that only E-diastreoisomers are formed. The ratio of the
isomers formed was determined from the proton NMR
spectrum. In each case, it was observed that the major iso-
mer formed resonates at higher field and the ratio was
found to be 2:1. The stereochemistry could not be un-
ambiguously established, as the diastereoisomers were
not separable by column chromatography.
To conclude we have proved that sodium tungstate–H2O2
is a highly efficient oxidant for oxidation of imine to ox-
aziridine. The oxidation proceeds stereospecifically and
yields only the E-isomer. Therefore this system is a rela-
tively cheap, single phase and useful alternative method
for oxidation of imines to oxaziridines.
References
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(16) General Procedure.
To a solution of aldimine (1 mmol) in MeCN (5 mL) and
sodium tungstate (10 mol%) was added 30% H2O2 (0.15
mL) dropwise at r.t. The progress of the reaction was
monitored by TLC. After the completion of the reaction, the
solvent was removed in vacuo, any excess H2O2 was
quenched with sat. Na2SO3 solution and the product was re-
extracted with CHCl3. The solvent was dried over
Na2SO4(anhyd) and evaporated. The crude product was
purified by column chromatography on silica gel using
mixtures of hexane and EtOAc.
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Synlett 2005, No. 7, 1176–1178 © Thieme Stuttgart · New York