Bromamine-T/RuCl3 as an efficient system for the oxidation of tertiary amines to N-oxides

Article abstract of DOI:10.1016/j.tetlet.2004.04.014

A variety of tertiary amines were efficiently and selectively oxidized to the corresponding N-oxides by bromamine-T using ruthenium trichloride as catalyst in alkaline (pH8.4) acetonitrile/water (1:1) at 80°C.

Full text of DOI:10.1016/j.tetlet.2004.04.014

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4281–4283
Bromamine-T/RuCl3 as an efficient system for the
oxidation of tertiary amines to N-oxides
Vishal B. Sharma, Suman L. Jain and Bir Sain*
Chemical and Biosciences Division, Indian Institute of Petroleum, Dehradun-248 005, India
Received 30 January 2004; revised 1 April 2004; accepted 5 April 2004
Abstract—A variety of tertiary amines were efficiently and selectively oxidized to the corresponding N-oxides by bromamine-T using
ruthenium trichloride as catalyst in alkaline (pH 8.4) acetonitrile/water (1:1) at 80 °C.
Ó 2004 Elsevier Ltd. All rights reserved.
N-Halo-N-metallosulfonamides, due to their ability to
act as sources of halonium cations, hypohalite species,
and N-anions, which actboth as bases and nucleophiles,
have proved to be valuable intermediates for a variety of
functional group transformations.1 Bromamine-T and
other related reagents act as strong oxidants both in
alkaline and acidic media and have been widely used for
the oxidation of alcohols,2 aldehydes,3 primary amines,4
thiols,5 and esters.6 N-Oxides are synthetically impor-
tant building blocks and are extensively used as oxi-
dants.7 A variety of stoichiometric8 as well as catalytic
methods are reported in the literature for the oxidation
of tertiary nitrogen compounds to N-oxides.9 In con-
tinuation of our studies on oxidation,9i;j;10 we report
herein a new and simple method for the oxidation of a
variety of tertiary nitrogen compounds 1 to N-oxides 2
in near quantitative yields using bromamine-T as oxi-
dant and ruthenium trichloride as the catalyst (Scheme
1).
Oxidation of a variety of tertiary nitrogen compounds
was achieved by using a catalytic amount of ruthenium
trichloride in acetonitrile/water (1:1) at 80 °C with
bromamine-T, the substrate/bromamine-T ratio being
(1:1.2) under alkaline pH (8.4) to yield N-oxides in
excellentyields. 11 These results are summarized in Table
1. In general substituted anilines were found to be more
reactive compared to pyridines and among substituted
pyridines those substituted with electron donating
groups were found to be more reactive and required
shorter reaction times for their oxidation.
The reaction was found to be highly dependent upon the
pH of the system. To evaluate the effect of pH, oxidation
of 4-picoline was carried outunder similar conditions at
different pH’s. At neutral pH, the oxidation of 4-picoline
was found to be very slow and the reaction required 8 h,
while at pH 8.4 the reaction was complete within 4.5 h. It
was also observed that at higher pH’s (9–11) the rate of
the reaction became very slow and was not com-
plete even after 12 h. This type of pH dependent
behavior for bromamine-B has been reported in the
literature.12 The oxidation of 4-picoline was found to be
very slow at room temperature (20 °C) requiring 10 h for
completion.
R
R
R
R
R
R
O-
N+
RuCl3 / Bromamine-T
N
Acetonitrile/water (1:1), 80 C
˚
pH (8.4)
The effectof various solvenst was also sutdied using
4-picoline as substrate. Among the solvents examined
[acetonitrile, 1,2-dichloromethane, ethanol, and an ace-
tonitrile/water (1:1) mixture], the mixture of acetonitrile/
water (1:1) was found to be the best solvent system,
perhaps due to the high dielectric constant of water.
1
2
Scheme 1.
Keywords: Bromamine-T; Ruthenium trichloride; Tertiary nitrogen
compounds; N-Oxides; Oxidation.
The oxidation of 4-picoline was found to be very slow
using chloramine-T in place of bromamine-T under
* Corresponding author. Tel.: +91-1352660071; fax: +91-1352660202;
e-mail: birsain@hotmail.com
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.014

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V. B. Sharma et al. / Tetrahedron Letters 45 (2004) 4281–4283
Table 1. Oxidation of tertiary nitrogen compounds to N-oxidesa
thankful to CSIR, New Delhi for the award of research
fellowships.
Entry
1
Substrate
Time (h)
3.0
Yield (%)b
75
N
CH3
References and notes
2
3
4
2.5
3.0
6.0
85
80
50
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N
N
CH3
6
7
12
N
C2H5
C2H5
N
N
8
2.5
2.5
5
CH3
CH3
9
10
(C2H5)3N
a Reaction conditions: substrate/bromamine-T (1:1.2), RuCl3ÆxH2O
(0.5 mol %), acetonitrile/water (1:1), pH 8.4 at 80 °C.
b Isolated yields.
similar reaction conditions. The enhanced reactivity of
bromamine-T is probably due to the weak bonding
between nitrogen and bromine.
Although mechanism of this reaction is not clear at this
stage, the reaction probably involves the RuCl3 cata-
lyzed formation of HOBr from bromamine-T in aque-
ous alkaline medium,13 which effects the oxidation of
tertiary amine to N-oxide.
In summary, we have developed a simple ruthenium
catalyzed oxidation of tertiary nitrogen compounds to
N-oxides using bromamine-T as oxidantunder mild
reaction conditions.
11. Typical experimental procedure: To a stirred solution of 4-
picoline (0.93 g, 10 mmol), bromamine-T (12 mmol, 3.2 g)
in alkaline (pH 8.4) acetonitrile/water (1:1) mixture
(15 mL), RuCl3ÆxH2O (1 mg, 0.5 mol %) was added and
the mixture was heated at 80 °C for 2.5 h. The reaction
progress was monitored by TLC (SiO2) gel. After com-
pletion of the reaction, the solvent was evaporated under
reduced pressure and the residue was dissolved in dichlo-
romethane. The dichloromethane layer was washed twice
with water and dried over sodium sulfate. The solvent was
evaporated under reduced pressure and the residue thus
Acknowledgements
We are thankful to the Director, IIP for his kind per-
mission to publish these results. S.L.J. and V.B.S. are

V. B. Sharma et al. / Tetrahedron Letters 45 (2004) 4281–4283
4283
obtained was purified by passing through a short silica gel
column using dichloromethane as eluent. Evaporation of
the solvent yielded 4-picoline N-oxide (0.92 g, 85%). Other
nitrogen compounds were oxidized using this procedure
and their reaction times and yields are given in Table 1.
The products were identified by comparing their physical
and spectral data with those of authentic samples reported
in the literature.
12. Subbiah, M.; Sockalingam, R. M. J. Mol. Catal. 2000,
160, 269.
13. Hardy, F. E.; Johnston, J. P. J. Chem. Soc., Perkin Trans.
2 1973, 742.