P. C. Heath et al. / Tetrahedron Letters 42 (2001) 1607–1610
1609
Scheme 2.
References
Treatment of thiocarbanilide (5) with methyl malonyl
chloride in refluxing 1,2-dichloroethane led primarily to
the formation of phenylisothiocyanate (8) and the
mixed ester amide (9) (Scheme 2). The identity of 8 and
9 were established by GC/MS. The identity of 9 was
also confirmed by comparison to an authentic sample
of the mixed amide ester prepared by the reaction of
aniline with methyl malonyl chloride. Compounds 8
and 9 were thought to be formed through thermal
rearrangement of the intermediate N-acylthiourea (6).
We overcame the thermal instability of 6 by performing
the reaction at 23–25°C with 2 equiv. of methyl mal-
onyl chloride in methylene chloride. A slow stream of
nitrogen was passed over the reaction mixture to
remove HCl formed during the reaction. This modified
protocol provided high yields of 6. However, treatment
of 6 with aqueous NaOH at 23–25°C again led primar-
ily to the formation of 8 and 9. Noting earlier that 3
cyclized spontaneously to 4 when isolated as an oil, 6
was similarly concentrated to an oil. After concentra-
tion to an oil, 6 cyclized to 7 over the course of several
days at 23–25°C. The crude product (7) was purified by
reslurrying in hot methyl t-butyl ether. The modified
protocol afforded excellent yields of 1,3-diaryl substi-
tuted-2-thiobarbituric acids (Table 1, entries 5–7).13
However, the sterically congested 1,3-di-o-tolyl
thiourea produced only a moderate yield of product
(entry 8).
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refluxing ethanol containing sodium ethoxide using the
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Acknowledgements
We would like thank Jerry Misner, Marvin Hansen,
Michael Martinelli, Tony Zhang, Eric Moher and
Andrew Fray for helpful discussions during the course
of this work.
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