J . Org. Chem. 1999, 64, 1713-1714
1713
Consequently, there is a need for the development of
protocols using readily available and safer reagents
which lead to high production of nitrile compounds. In
view of the current thrust on catalytic processes, there
is merit in developing a truly catalytic transformation
of amides to nitriles using inexpensive reagents. We
report herein a neutral and relatively simple new method
for effecting this transformation by using various orga-
notin oxides under microwave irradiation.
In recent years, microwave-induced rate acceleration
technology is becoming a powerful tool in organic syn-
thesis11 because of milder reaction conditions, enhanced
selectivity, and associated ease of manipulation. Some
recent applications include intramolecular Diels-Alder
reactions,12 solid-phase peptide synthesis,13 hydrolysis of
esters14 and silyl ethers,15 N-Boc deprotection,16 etc.
Organostannyl oxides have been widely used for the
selective manipulation of hydroxyl groups and polyols,
particularly in the area of carbohydrates and polyhy-
droxylated compounds, where preparative procedures
typically have to cope with repeated protection/deprotec-
tion steps.17 To the best of our knowledge, however, the
generality and applicability of organostannyl oxides in
the preparation of nitriles from primary amides under
microwave irradiation is not known.
In connection with our current endeavors toward the
synthesis of biologically interesting natural products,18
we explored the opportunity to examine the effect of
microwave irradiation on the formation of nitriles. The
results of the tin-mediated preparation of nitriles using
catalytic amounts of dibutyltin oxide in toluene are
illustrated in Table 1. In all the cases examined, the
formation of the nitrile is very fast, requiring less than
15 min of overall irradiation time in the microwave oven.
The main advantage of our procedure is evident when
one compares the reaction time for the formation of
nitriles from the primary amides under microwave heat-
ing (10-15 min) with that for the standard conditions
(overnight in refluxing toluene under standard thermal
conditions).19 In contrast to the previously reported
methods, no strong dehydration or expensive reagent is
needed, and the reaction can be easily carried out on a
large scale under neutral conditions.
Rea gen ts for Or ga n ic Syn th esis: Use of
Or ga n osta n n yl Oxid es a s Ca ta lytic Neu tr a l
Agen ts in th e P r ep a r a tion of Nitr iles fr om
P r im a r y Am id es u n d er Micr ow a ve
Ir r a d ia tion †
D. Subhas Bose* and B. J ayalakshmi
Organic Chemistry Division III, Indian Institute of
Chemical Technology, Hyderabad 500 007, India
Received September 9, 1998
The conversion of primary alkyl or aryl amides to their
corresponding nitriles constitutes a very useful functional
group transformation, and the plethora of reagents for
this transformation documented in literature directly
demonstrates the importance with which this functional
group transformation has been addressed. As early as
1945, this reaction was reviewed,1 and since then,
dehydrating reagents and alternate conditions providing
higher yields have been introduced.2 Many of these
reported methods, however, require the use of highly
reactive reagents or harsh conditions in acidic or basic
media, or they involve tedious workup procedures. Phos-
phorus pentoxide3 has been the most common agent for
the dehydration of primary amides to nitriles, but many
others, including thionyl chloride4 or phosphorus oxy-
chloride,5 are usually employed.
Recently, alkylating and dehydrating reagents have
been introduced that permit the reaction to proceed under
mild,6 neutral conditions7 and at lower temperature8 or
in liquid triphasic systems.9 Unfortunately, the reagents
employed so far require special preparation, and the
methods are generally limited to only arylamides.10
* To whom correspondence should be addressed. Fax: +91-40-
7173387/7173757. E-mail: root@csiict.ren.nic.in.
† IICT Communication 4137.
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Zabicky, J ., Ed.; J ohn Wiley and Sons: New York, 1970. (b) Larock,
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York, 1989.
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1993, 34, 1581. (b) Rigo, B.; Lespagnol, C.; Pauly, M. Tetrahedron Lett.
1986, 27, 347. (c) Campagna, F.; Carroti, A.; Casini, G. Tetrahedron
Lett. 1977, 21, 1813. (d) Bose, D. S.; Goud, P. R. Tetrahedron Lett. 1999,
40, 747.
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E.; Sugasawa, S. Tetrahedron Lett. 1970, 4383. (c) Ficken, G. E.;
France, H.; Linstead, R. P. J . Chem. Soc. 1954, 3731. (d) Bose, D. S.;
Venkat Narsaiah, A. Tetrahedron Lett. 1998, 39, 6533. (e) Bose, D. S.;
J ayalakshmi, B. Synthesis (in press).
The mechanism by which these reactions proceed is
particularly intriguing, and we could find no literature
precedence for nitrile formation from the amides using
(10) (a) Hendrickson, J . B.; Schwartzman, S. M. Tetrahedron Lett.
1975, 277. (b) Yokoyama, M.; Yoshida, S.; Imamoto, T. Synthesis 1982,
591. (c) Kim, S.; Yi, K. Y. Tetrahedron Lett. 1986, 22, 1925.
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Catalysts in Organic Synthesis; Smith, K., Ed.; Ellis Horwood: New
York, 1992; pp 302-326. (b) Caddick, S. Tetrahedron 1995, 51, 10403.
(12) Wang, W. B.; Roskamp, E. J . Tetrahedron Lett. 1992, 33, 7631.
(13) Yu, H. M.; Chen, S. T.; Wang, K. T. J . Org. Chem. 1992, 57,
4781.
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1993, 34, 4603.
(15) Varma, R. S.; Lamture, J . B.; Varma, M. Tetrahedron Lett. 1993,
34, 3029.
(16) Bose, D. S.; Lakshminarayana, V. Tetrahedron Lett. 1998, 39,
5631.
(8) (a) Bagar, T. M.; Riley, C. M. Synth. Commun. 1980, 10, 479.
(b) Mai, K.; Patil, G. Tetrahedron Lett. 1986, 27, 2203. (c) Olah, G. A.;
Narang, S. C.; Fung, A. P.; Gupta, B. C. G. Synthesis 1980, 657. (d)
Saednya, A Synthesis 1985, 184.
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1992, 57, 4555.
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Pereyre, M.; Quintard, J .-P.; Rahm, A. Tin in Organic Synthesis;
Butterworth: London, 1987; pp 261-285. (c) Morcuende, A.; Valverde,
S.; Herradon, B. Synlett. 1994, 89.
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(19) Bose, D. S.; J ayalakshmi, B. Unpublished results.
10.1021/jo981839o CCC: $18.00 © 1999 American Chemical Society
Published on Web 02/10/1999