Scheme 2 Plausible mechanism for PSCl3 mediated formation of thioamides from ketoximes.
compiled in Table 1.z Symmetrical aromatic ketoximes such as
benzophenone oxime underwent very smooth transformation
with excellent yield. A cyclic oxime i.e. cyclohexanone oxime
provided a moderate yield of azepane-2-thione. The other
cyclic oxime investigated in this study, cyclododecanone
oxime, was transformed into azacyclotridecane-2-thione in
good yield. In all cases studied, exclusive anti migration, as
expected, was observed. Oximes containing a syn and anti
mixture resulted in the formation of two thioamides in
proportion to the initial concentration (Table 1, entry 11).
Acetone oxime, which has often been found a difficult substrate
for BR,7 underwent easy transformation and the corresponding
thioamide was obtained in good yield. Various functional
groups such as halide, nitro, methyl and methoxy were well
tolerated under the reaction conditions. The only side product
formed was the corresponding ketone in some cases.
and the reaction was found to be of general applicability.
These findings allow the exploring of BR further with diverse
reagents to produce a variety of products.
We thank Mr Basant Lal and Mr Avik Mazumder for
NMR analysis and Mr L. N. S. Tomar for assistance in
GC-MS analysis. We also gratefully acknowledge Dr R.
Vijayaraghavan for his kind support and encouragement.
Notes and references
z General procedure: 7.5 mmol of PSCl3 was mixed with an equimolar
amount of water. This was followed by the dropwise addition of
11.25 mmol of triethylamine at 0–5 1C with constant mixing. To this
mixture 5 mmol of oxime was added in parts and mixed for a further
3–5 min keeping the temperature below 60 1C. The reaction mixture
was then heated at a temperature indicated in Table 1. On completion
of the reaction, the contents were mixed with silica, loaded on a
column and eluted with hexane–ethyl acetate (80 : 20). Removal of the
solvent under vacuum afforded pure compound.
Our probable working mechanistic rationale, which is based
on the literature precedents,2,3b,9 is depicted in Scheme 2. For
the formation of intermediate nitrilium ion C, there could be
two possible pathways that can be considered. One is the
route a in which first an ester B is formed from oxime and
thiophosphoryl chloride with the liberation of HCl. The HCl
generated then attacks B immediately which leads to N–O
bond fission resulting in the formation of nitrilium ion C and
chlorothiophosphoric acid D. Alternatively, C can also be
generated by following route b in which initially oxime is
activated by protonation (step 1) followed by loss of water
(step 2). Now the cationic intermediate C may be attacked by
the either of the nucleophiles present in the reaction medium i.e.
chlorothiophosphoric acid D or water. Attack on C by D will
lead to thioamide formation whereas attack by water will
result in the formation of amide. We observed that at higher
temperature formation of thioamides, i.e. attack by chloro-
thiophosphoric D, predominates. Further, we presume that an
increase in temperature may assist the hydrolysis of thiophosphoryl
chloride by water itself and due to this simultaneous reaction,
water availability is reduced. But, still a small fraction of water
is able to combine with C to form H. Since, under these
reaction conditions H can be conveniently converted to F,
ultimately all the steps lead to smooth formation of F.
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In conclusion, PSCl3 has been explored as a uniquely
capable reagent to transform ketoximes into thioamides. It is
used as a dual purpose reagent to induce BR as well as to
capture the intermediate nitrilium ion eventually to generate
N-substituted thioamides. Diverse ketoximes were investigated
9 P. Sykes, A Guide Book to Mechanism in Organic Chemistry,
Pearson Education, Singapore, 1986, p. 123.
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 5409–5411 | 5411