ISSN 1070-4272, Russian Journal of Applied Chemistry, 2006, Vol. 79, No. 4, pp. 631!633. + Pleiades Publishing, Inc., 2006.
Original Russian Text + I. P. Pogorelova, V. D. Orlov, A. D. Isak, 2006, published in Zhurnal Prikladnoi Khimii, 2006, Vol. 79, No. 4,
AND INDUSTRIAL ORGANIC CHEMISTRY
Synthesis of 6-Methyluracil-5-sulfonyl Chloride
I. P. Pogorelova, V. D. Orlov, and A. D. Isak
Rubezhnoe Branch, Dal’ East-Ukrainian National University, Rubezhnoe, Lugansk oblast, Ukraine
Received November 25, 2005
Abstract-Sulfochlorination of 6-methyluracil with chlorosulfonic acid in the presence of thionyl chloride
was studied. The lactam3lactim tautomerism of 6-methyluracil was considered. Ways to increase the yield
of the sulfonyl chloride were suggested. The mechanism of the effect exerted by thionyl chloride additions
Sulfochlorination reactions are widely used in or-
ganic (in particular, pharmaceutical) chemistry. Sulfo-
nyl chlorides are intermediates in syntheses of active
and dispersible dyes, herbicides, and fungicides .
Among six-membered heterocyclic compounds con-
taining two nitrogen atoms, a prominent place is occu-
pied by pyrimidine derivatives used as drugs (sulf-
amide drugs such as Sulfadimethoxine, Sulfamono-
methoxine; antitumor agent Fluorouracil; antibiotic
Amecytin, etc.) [2, 3].
Of particular interest in this respect is readily avail-
able methyluracil, which is used in syntheses of sul-
fonamides, sulfonyldiureides, sulfonylhydrazides, and
sulfonates; some of these compounds showed biologi-
Data on sulfochlorination of 6-methyluracil are
relatively few. As shown in [43 6], uracil and 6-meth-
yluracil 1 react with a tenfold excess of chlorosulfonic
acid to form uracil-6-sulfonyl chloride and 6-methyl-
uracil-5-sulfonyl chloride 2 in a low yield (<22%).
To develop a more efficient procedure for prepar-
ing 6-methyluracilsulfonyl chloride, we examined
the effect of various factors on the sulfochlorination
of 1 [7, 8].
At 30oC, compound 1 does not noticeably react
with chlorosulfonic acid; the reaction starts only at
35oC, and the yield of 2 under these conditions does
not exceed 15%. With increasing temperature, the re-
action rate and sulfonyl chloride yield increase, but
even after the sulfochlorination for 7 h at 75oC the
yield of 2 does not exceed 28% (see figure). When
the reaction mixture is poured onto ice to isolate the
product, a considerable part of 2 undergoes hydrolysis
and transforms into 6-methyluracilsulfonic acid, which
was isolated from the solution by salting-out with
NaCl. Thus, the desired sulfonyl chloride is unstable
and is readily hydrolyzed in aqueous solution. To sup-
press the hydrolysis, the reaction mixture was poured
onto a 1 : 1 mixture of ice and acetic acid.
It was found in [9, 10] that the use of chlorosulfon-
ic acid in combination with thionyl chloride (volume
ratio 1.5 : 1) considerably increases the rate of forma-
tion and yield of 2 (see figure). In contrast to SOCl
addition of SO
does not noticeably af-
Yield of 6-methyluracilsulfonyl chloride W vs. time t
(1! 4) in the absence and (5!9) in the presence of thionyl
chloride. T, oC: (1, 5) 45, (2, 6) 55, (3, 7) 65, (4, 8) 75,
and (9) 85.