and selectively antagonizing the human R1A receptors,4d to
name a few. This has led to the development of several new
methods5 for promoting the Biginelli reaction, including solid
phase reactions6a-c and microwave irradiation.6d
Application of ꢀ-Oxodithioesters in Domino and
Multicomponent Reactions: Facile Route to
Dihydropyrimidines and Coumarins
The Lewis acid-catalyzed Biginelli reaction has also achieved
considerable success. The use of a number of catalysts such as
BF3Et2O,7a FeCl3 · 6H2O,7b LiBr,7c ZnCl2,7d BiCl3,7e
LaCl3 ·7H2O,7f Mn(OAC)3 ·2H2O,7g InCl3,7h Cu(OTf)2,7i lan-
Okram Mukherjee Singh* and Nepram Sushuma Devi
Department of Chemistry, Manipur UniVersity,
Canchipur-795003, India
7k
thanide triflates,7j ZrCl4, YbIII resin,7l CeCl3 ·7H2O,7m LiClO4,7n
RuCl3,7o SmI2,7p Sr(OTf)2,7q La(OTf)3, or Yb(OTf)3 in the
presence of a chiral Yb catalyst7r has been reported to be
effective for this one-pot reaction.
ReceiVed NoVember 25, 2008
However, to our knowledge the new methodologies in all
these reported methods use only the ꢀ-ketoesters such as ethyl
acetoacetate or methyl acetoacetate and variations are designed
only in the structures of the substituted aldehydes. As a result,
the structures of known dihydropyrimidines either in improved
yields or by the application of new techniques are always
reported.7a-r We are reporting herein the application of ꢀ-ox-
odithioesters8 in Biginelli reactions under solvent-free conditions
to synthesize the hitherto unreported dihydropyrimidinones in
excellent yields. Also described herein is an expedient synthesis
of a novel series of coumarines using ꢀ-oxodithioesters as an
unprecedented substrate for the Knovenagel type of cyclocon-
densation.
ꢀ-Oxodithioesters 3 are generally prepared by reacting any
active methylene compound with CS2 in the presence of a
suitable base followed by alkylation with either dimethylsulfate
or methyl iodide. This method gives poor yields and also
mixtures of dithioesters and ketene dithioacetals. Thus improved
yields of ꢀ-oxodithioesters are obtained by treating active
methylene compounds 1 with (S,S)-dimethyl trithiocarbonate
A facile route to hitherto unknown 5-methylmercaptothio-
carbonyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones and sub-
stituted 2H-chromene-2-thiones has been developed. SnCl2-
catalyzed cyclocondensation of ꢀ-oxodithioesters with a
variety of readily accessible aldehydes and urea affords the
dihydropyrimidinones. The methodology involves the three-
component Biginelli reaction. On the other hand, substituted
salicylaldehyde and ꢀ-oxodithioesters reacted under the same
condition to afford the substituted 2H-chromene-2-thiones
in high yields.
Domino processes and multicomponent reactions (MCRs),
in an environmentally benign and atom-economic fashion, play
important roles in organic synthesis, especially for the synthesis
of bioactive heterocycles.1 Polyfunctionalized dihydropyrim-
idines are prepared by a multicomponent reaction that was first
reported by Biginelli in 1893, involving a one-pot condensation
of an aldehyde, ꢀ-ketoester, and urea under strongly acidic
conditions.2 Considerable interest in this transformation has
steadily increased over the past decade3 owing to their remark-
able pharmacological properties such as calcium channel
modulatory activity,4a,b inhibiting the platelet activating factor,4c
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Published on Web 03/20/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 3141–3144 3141