6086
J . Org. Chem. 1998, 63, 6086-6087
Rea ction s of Th ioa r oylk eten e S,N-Aceta ls
w ith 1,3-Dica r bon yl Com p ou n d s in th e
P r esen ce of Mer cu r y(II) Aceta te: A Gen er a l
Rou te to 2-Acyl- a n d 2-Ar oyl-3-(a lk yla m in o)-5-
a r ylth iop h en es a n d 2-(Eth oxyca r bon yl)-3-
(m eth yla m in o)-5-a r ylth iop h en es
Bo Sung Kim, Kyung Seok Choi, and Kyongtae Kim*
Department of Chemistry, Seoul National University,
Seoul 151-742, Korea
Received May 27, 1998
Acyl- and aroylketene S,N-acetals have been extensively
studied by J unjappa and co-workers1 and utilized for the
synthesis of a variety of heteroatom compounds. Surpris-
ingly, much less attention has been focused on their ana-
logues, thioaroylketene S,N-acetals 1.2 This might be due
to the difficulty of access to the compounds 1. Recently, we
reported a facile and convenient method for the synthesis
of compounds 1, which involves the reactions of 2-alkyl-3-
(alkylthio)-5-arylisothiazolium iodides with NaBH4 in a
mixture of CHCl3 and EtOH at room temperature.3 We have
shown that compounds 1 are useful for the synthesis of
various heterocyclic compounds.4
F igu r e 1. ORTEP drawing of 1b.
As a part of our study on exploring the synthetic potential
of compounds 1, 3-(methylamino)-3-(methylthio)-1-phenyl-
thioxopropene (1a ) (0.172 mmol) was treated with mercu-
ry(II) acetate (0.172 mmol) in acetone (10 mL) for 1 h at
room temperature in order to obtain information about a
possible interaction between mercury(II) ion and the thione
sulfur. Chromatography (silica gel, 70-230 mesh, ASTM)
of the reaction mixture gave 2-acetyl-3-(methylamino)-5-
phenylthiophene (2a ) in 75% yield. The involvement of
acetone as a reagent in this reaction prompted us to
investigate the reactions of 1 with readily enolizable 1,3-
dicarbonyl compounds. We report the preliminary results.
2-Acylthiophenes can be readily synthesized by acylation
with acyl anhydrides or acid chlorides, using mild Friedel-
Craft catalysts, acylations of 2-thienylmetal derivatives, or
the reaction of 2-thenoyl chloride with organocadmium.6
However, synthesis of 2-acyl- and 2-aroyl-3-aminothiophenes
has received little attention. It appears to be another report
that involves the reaction of the condensation product of
malononitrile and carbonoxy sulfide in sodium ethoxide
solution, with phenacyl bromide, giving 3-amino-2-benzoyl-
4-cyano-5-hydroxythiophene.7 This method is, however, not
applicable to the synthesis of compounds 2.
It is noteworthy that a benzoyl (R4 ) Ph) group and a
trifluoroacetyl (R4 ) CF3) group are removed from unsym-
metrical 1,3-diketones, i.e., 1-phenyl-1,3-butanedione and
1,1,1-trifluoro-2,4-pentanedione, in the course of the reaction
leading to compounds 2a (Table 1, entry 2) and 2g-j (Table
1, entries 8-11), respectively.
Similarly, compounds 1 (0.13-0.31 mmol) reacted with
ethyl acetoacetate (1.5 molar equiv) under the same condi-
tions to give 5-aryl-2-(ethoxycarbonyl)-3-(methylamino)-
thiophenes 3 in excellent yields. Yields and melting points
of 3 are summarized in Table 2.
Synthesis of 2-(alkoxycarbonyl)-3-aminothiophenes has
been achieved by treatment of either â-chlorocinnamonitriles
with thioglycolic acid esters in the presence of a base8 or a
base-catalyzed cyclization of â-alkylthio-R-cyanocinnamoni-
triles.9 Treatment of 2,5-diphenylisothiazolium perchlorate
with dimethylsulfonium carbethoxymethylide gave 2-(ethox-
ycarbonyl)-5-phenyl-3-(phenylamino)thiophenes as a minor
product.10
The stereochemistry of compounds 1 has been established
by an X-ray crystallographic analysis of 3-(benzylthio)-3-
(methylamino)-1-phenylthioxopropene (1b), which shows
clearly that the CdS bond and the methylamino group are
syn to each other (Figure 1).
Treatment of a mixture of compounds 1 (0.17-0.31 mmol)
and mercury(II) acetate (1.5 molar equiv) in CH2Cl2 (10-
15 mL) with 1,3-diketones (0.2-1.0 mmol) at room temper-
ature gave 2-acyl- and 2-aroyl-3-(alkylamino)-5-arylthio-
phenes 2 in good to moderate yields. Yields and melting
points of 2 are summarized in Table 1.
Compounds 2 are all new except for 2g.5 The structures
of compounds 2 were determined on the basis of the
spectroscopic and mass spectral data and elemental analy-
ses.
It is interesting to find that treatment of 1 with methyl
phenylsulfinyl acetate under the same conditions as for 3
gave 3d in 89% yield, whereas with ethyl methanesulfonyl
(1) J unjappa, H.; Ila, H.; Asokan, C. V. Tetrahedron 1990, 46, 5423.
(2) (a) Hervieu, G.; Rioult, P.; Vialle, J . Bull. Soc. Chim. Fr. 1971, 12,
4380. (b) Hassan, M. E.; Magraby, M. A.; Aziz, M. A. Tetrahedron 1985,
41, 1885. (c) Bachers, G. E.; McKinnon, D. M.; Buchshriber, J . M. Can. J .
Chem. 1972, 50, 2568.
(3) Kim, S. H.; Kim, J .; Kim, J . H. J . Heterocycl. Chem. 1993, 30, 929.
(4) Kim, S. H.; Ra, Y. H.; Lee, Y. Y.; Kim, K. J . Heterocycl. Chem. 1994,
31, 1361.
(6) Campaigne, E. In Comprehensive Heterocyclic Chemistry; Katritzky,
A., Rees, C. W., Eds.; Pergamon Press: Oxford, 1984; Vol. 4, 3.15, p 864-
934.
(7) Scha¨fer, H.; Gewald, K. J . Prakt. Chem. 1975, 317, 337.
(8) Hartmann, H.; Liebscher, J . Synthesis 1984, 275.
(9) Gewald, K.; Hain, U. Monatsh. Chem. 1992, 23, 455.
(10) McKinnon, D. M.; Duncan, K. A.; Millar, L. M. Can. J . Chem. 1984,
62, 1580.
(5) McKinnon, D. M.; Hassan, M. E. Can. J . Chem. 1973, 51, 3081.
S0022-3263(98)01043-3 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/19/1998