Organic &
Biomolecular
Chemistry
Cite this: Org. Biomol. Chem., 2011, 9, 379
COMMUNICATION
A direct and efficient preparation of 1-phenyltetrazol-5-yl sulfides from
alcohols†
Adam R. Ellwood and Michael J. Porter*
Received 11th October 2010, Accepted 1st November 2010
DOI: 10.1039/c0ob00863j
Treatment of primary or secondary alcohols with 1-phenyl-
1(H)-tetrazole-5-thiol and [Me2NCHSEt]+ BF4- leads directly
and cleanly to 1-phenyl-1(H)-tetrazol-5-yl sulfides.
thioformamide salt as an activating reagent for alcohols. The by-
products generated in the reaction are volatile and/or highly polar,
facilitating work-up and product purification.
We recently reported that treatment of alcohols 2 with the
methylsulfanyliminium iodide 3, in the presence of imidazole, led
to formation of alkyl iodides 4 (Scheme 2).8
The preparation of alkenes from aldehydes or ketones and a-
sulfonyl carbanions, known as the Julia olefination reaction,1 is a
widely used process. In the original Julia protocol,2 deprotonation
of an alkyl aryl sulfone and addition to an aldehyde was followed
by a separate reductive step to form the alkene.
A major advance in Julia olefination chemistry was the develop-
ment of a number of modified procedures in which the reaction of
an anion derived from an alkyl heteroaryl sulfone with an aldehyde
led directly to an alkene as product, obviating the need for a
second reductive step.3 Foremost among these procedures is that of
Kocien´ski, which uses alkyl tetrazol-5-yl sulfones 1 (Scheme 1).4,5
Scheme 2 Iodination of alcohols with iminium salt 3.
We reasoned that if the iodide counterion in 3 were replaced
with a non-nucleophilic anion such as tetrafluoroborate, the
resulting salt should still react with alcohols to afford an activated
intermediate; in the absence of iodide, however, it should be
possible to introduce other nucleophiles to displace the leaving
group. 1-Phenyl-(1H)-tetrazole-5-thiol was selected as such a
nucleophile.
To prepare the requisite activating reagent, N,N-
dimethylthioformamide 5 was treated with triethyloxonium
tetrafluoroborate in dichloromethane to afford the salt 6, which
precipitated as a crystalline solid on addition of the reaction
mixture to diethyl ether (Scheme 3).‡
Scheme 1 The Julia–Kocienski olefination.
The sulfones 1 are invariably prepared by oxidation of the
corresponding sulfides, which in turn are generally synthesised
from alcohol precursors by one of two methods: either through the
intermediacy of an activated alcohol such as a halide or a sulfonate,
or by use of the Mitsunobu reaction with a tetrazole-5-thiol as the
nucleophilic component.4,6 The former method requires multiple
operations, while the latter suffers from the production of an
equimolar quantity of triphenylphosphine oxide, which can cause
difficulties in purification.
Scheme 3 Preparation of tetrafluoroborate salt 6.
A third method for the conversion of alcohols to tetrazolyl
sulfides is by reaction with a bis-tetrazolyl dithiocarbonate.
This method, however, is only applicable to allylic and benzylic
alcohols.7
In this paper, we describe a new procedure for the direct
conversion of alcohols into tetrazolyl sulfides, using an S-alkylated
Initial investigations into sulfide formation were carried out
with ethyl 6-hydroxyhexanoate 2a as substrate. This alcohol was
treated with 1-phenyl-(1H)-tetrazole-5-thiol 7 (1.2 equivalents),
salt 6 (1.5 equivalents) and imidazole (0.5 equivalents) in a variety
of solvents at elevated temperature (Table 1, entries 1–4).
In all cases, clean conversion of the alcohol to sulfide 8a was
observed. Of the solvents investigated, conversion was most rapid
in toluene and acetonitrile, and toluene was chosen as the solvent
for further optimisation.
Department of Chemistry, University College London, 20 Gordon Street,
London, WC1H 0AJ, UK. E-mail: m.j.porter@ucl.ac.uk; Fax: +44 20 7679
7463; Tel: +44 20 7679 4710
† Electronic supplementary information (ESI) available: Experimental
procedures, characterisation data and 1H and 13C NMR spectra for
compounds 6, 8a–k and 9. See DOI: 10.1039/c0ob00863j
By increasing the loading of imidazole and thiol in the reaction,
and lowering the amount of solvent, complete conversion of 2a to
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The Royal Society of Chemistry 2011
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