Superoxide-mediated regioselective deblocking of the tosyl group from N-tosylcarboxamides

Article abstract of DOI:10.1080/00397910600775416

In situ-generated tetraethylammonium superoxide brings about an easy and selective cleavage of the N-S bond of N-tosylcarboxamides, providing a new method for the deblocking of the tosyl group from such substrates. Copyright Taylor & Francis Group, LLC.

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Superoxide‐Mediated Regioselective
Deblocking of the Tosyl Group from
N‐Tosylcarboxamides
R. S. Raghuvanshi a & K. N. Singh a
a Department of Applied Chemistry , Institute of Technology, Banaras Hindu
University , Varanasi, India
Published online: 16 Feb 2007.
To cite this article: R. S. Raghuvanshi & K. N. Singh (2006) Superoxide‐Mediated Regioselective Deblocking
of the Tosyl Group from N‐Tosylcarboxamides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 36:20, 3075-3078, DOI: 10.1080/00397910600775416
To link to this article: http://dx.doi.org/10.1080/00397910600775416
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Synthetic Communicationsw, 36: 3075–3078, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600775416
Superoxide-Mediated Regioselective
Deblocking of the Tosyl Group from
N-Tosylcarboxamides
R. S. Raghuvanshi and K. N. Singh
Department of Applied Chemistry, Institute of Technology, Banaras
Hindu University, Varanasi, India
Abstract: In situ–generated tetraethylammonium superoxide brings about an easy and
selective cleavage of the N22S bond of N-tosylcarboxamides, providing a new method
for the deblocking of the tosyl group from such substrates.
Keywords: Detosylation, N-tosylcarboximide, superoxide
The importance of selective introduction and removal of protecting groups in
organic synthesis is well established.[1,2] The p-toluenesulfonyl(tosyl) group is
the best-known protecting group,[3] but its removal is not straightforward. The
removal of the tosyl group has been achieved by employing a variety of sub-
strates.[3–6] There are two methods for the reductive deblocking of the tosyl
group from N-tosylcarboxamides. The first method involves the electrochemi-
cal reduction of different types of N-tosylcarboxamides under various exper-
imental conditions,[7] the whereas the second one employs reductive
deprotection using lithium powder in the presence of a catalytic amount of
naphthalene in tetrahydrofuran (THF) at temperatures ranging between 278
and 208C.[5] The desulfonylation of N-sulfonylamide can be achieved by
the reaction of samarium(II) iodide (SmI2) in THF at room temperature[8]
and under neutral conditions by reaction with tributyltin hydride.[9]
In light of this and as a part of our ongoing research to extend the appli-
cability of the superoxide ion in organic synthesis,[10] we report herein a mild
Received in India February 8, 2006
Address correspondence to K. N. Singh, Department of Applied Chemistry,
Institute of Technology, Banaras Hindu University, Varanasi, India. E-mail:
knsinghbhu@yahoo.co.in
3075

3076
R. S. Raghuvanshi and K. N. Singh
and efficient deprotective method for N-tosylcarboxamide using in situ–
generated tetraethylammonium superoxide in dry DMF at room temperature
(Scheme 1).
In the present study, Et4NO2 has been generated in situ by the phase-
transfer reaction of KO2 and Et4NBr in dimethylformamide at room tempera-
ture and subsequently allowed to react with a number of N-tosylcarboxamides
(1a–g).
Various N-tosylcarboxamides, viz. N-benzoyl-p-toluenesulphonamide
(1a), N-p-toluoyl-p-toluenesulphonamide (1b), N-m-toluoyl-p-toluenesul-
phonamide (1c), N-o-toluoyl-p-toluenesulphonamide (1d), N-acetyl-p-
toluenesulphonamide (1e), N-propionyl-p-toluenesulphonamide (1f), and
N-butyryl-p-toluenesulphonamide (1g), were allowed to react with KO2
in the presence of Et4NBr in dry DMF at room temperature. The N-tosyl-
carboxamides (1a–g) undergo selective N22S bond cleavage to give the
corresponding amides (2a–g) and p-toluenesulphonic acid (3) in reason-
ably good yield under the mild reaction condition of Et4NO2.
A three-fold molar excess of KO2 and 1.5-fold molar excess of Et4NBr with
respect to the substrate were employed to achieve the cleavage. Each reaction
Scheme 1.

Regioselective Deblocking of the Tosyl Group
3077
was monitored by thin-layer chromatography (TLC) for its completion. The
products were fully identified by their melting points and spectral data,
which were in full agreement with the values described in the literature.
Thus, tetraethylammonium superoxide gives rise to the selective cleavage
of the N22S bond of the N-tosylcarboxamides, affording deprotected carbox-
amides and p-toluenesulphonic acid under mild and nonaqueous aprotic
conditions.
EXPERIMENTAL
Potassium superoxide and tetraethylammonium bromide were procured from
E. Merck, Germany, and were used as received. Dry N,N-dimethylformamide
˚
(DMF) from Aldrich, USA, was stored over molecular sieves (4 A) prior to
use. The other reagents and solvent were of A.R. grade. Substrates used in
the present investigation were prepared according to literature procedure.[11]
Reaction of In Situ–Generated Tetraethylammonium Superoxide
with N-Tosylcarboxamides (1a–g) General Procedure
Potassium superoxide (0.43 g, 0.006 mol) and tetraethylammonium bromide
(0.63 g, 0.003 mol) were weighted under a nitrogen atmosphere using an
atmosbag and transferred into a three-necked round-bottom flask equipped
with a magnetic stirrer, nitrogen inlet, and a Leibig condenser protected by
a calcium chloride drying tube. Dry dimethylformamide (30 ml) was added
to it, and the mixture was agitated magnetically for 15 min to facilitate the
formation of tetraethylammonium superoxide. Finally, the substrate N-tosyl-
carboxamide (0.002 mol) was admitted to it, and the stirring continued at
room temperature until the complete loss of the substrate was indicated by
TLC. The nitrogen gas was bubbled throughout to avoid atmospheric
moisture. After the reaction was over, mixture was treated with brine
solution (20 ml) to decompose the unreacted potassium superoxide.
Saturated sodium hydrogen carbonate solution (20 ml) was added to it, and
the solution was extracted with CHCl3 (3 Â 20 ml) and dried over
anhydrous Na2SO4, filtered, and evaporated to give the products (2a–g).
The aqueous phase was acidified with hydrochloric acid and extracted with
CHCl3 (3 Â 20 ml) to isolate the p-toluenesulphonic acid (3).
ACKNOWLEDGMENT
The authors thank Council of Scientific and Industrial Research (CSIR),
New Delhi, for financial support.

3078
R. S. Raghuvanshi and K. N. Singh
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