C-alkylation of Meldrum's acid using triphenyl phosphine and N-bromosuccinimide

Article abstract of DOI:10.1081/SCC-100107015

A simple and efficient method for the C-alkylation of Meldrum's acid by alcohol using triphenyl phosphine and N-bromosuccinimide is described. Primary alcohols yielded bis-alkylated Meldrum's acid whereas secondary alcohols yielded mono-alkylated Meldrum's acid.

Full text of DOI:10.1081/SCC-100107015

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C-ALKYLATION OF MELDRUM'S ACID USING TRIPHENYL
PHOSPHINE AND N-BROMOSUCCINIMIDE
Sameer P. Dhuru a , Nikhil U. Mohe a & Manikrao M. Salunkhe b
a Department of Chemistry , The Institute of Science , 15, Madam Cama Road, Mumbai,
400 032, India
b Department of Chemistry , The Institute of Science , 15, Madam Cama Road, Mumbai,
400 032, India
Published online: 16 Aug 2006.
To cite this article: Sameer P. Dhuru , Nikhil U. Mohe & Manikrao M. Salunkhe (2001) C-ALKYLATION OF MELDRUM'S ACID
USING TRIPHENYL PHOSPHINE AND N-BROMOSUCCINIMIDE, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 31:23, 3653-3657, DOI: 10.1081/SCC-100107015
To link to this article: http://dx.doi.org/10.1081/SCC-100107015
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SYNTHETIC COMMUNICATIONS, 31(23), 3653–3657 (2001)
C-ALKYLATION OF MELDRUM’S
ACID USING TRIPHENYL PHOSPHINE
AND N-BROMOSUCCINIMIDE
Sameer P. Dhuru, Nikhil U. Mohe,
and Manikrao M. Salunkhe*
Department of Chemistry, The Institute of Science,
15, Madam Cama Road, Mumbai – 400 032, India
ABSTRACT
A simple and efficient method for the C-alkylation of
Meldrum’s acid by alcohol using triphenyl phosphine and
N-bromosuccinimide is described. Primary alcohols yielded
bis-alkylated Meldrum’s acid whereas secondary alcohols
yielded mono-alkylated Meldrum’s acid.
Bis-alkylated Meldrum’s acids are important synthetic intermediates
and used in pharmaceuticals. They can be easily converted into malonic
esters or acids, ketones and barbiturates. They have also been used in the
generation of ketenes.
A number of methods have been reported for the C-alkylated deriva-
tives of Meldrum’s acid.1–7
* Corresponding author.
3653
Copyright & 2001 by Marcel Dekker, Inc.
www.dekker.com

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DHURU, MOHE, AND SALUNKHE
The triphenyl phosphine/N-bromosuccinimide reagent system has ear-
lier been used various Mitsunobu type reactions.8–11
In continuation of our work on triphenyl phosphine12 and interest
in Mitsunobu type reactions,13 we have developed a mild and efficient
method for the C-alkylated of Meldrum’s acid by alcohols using triphenyl
phosphine and N-bromosuccinimide. N-bomosuccinimide is very inexpen-
sive and non-hazardous as compared to diisopropylazodicarboxylate, which
was used in the Mitsunobu-alkylation of Meldrum’s acid.7
Polymer supported triphenyl phosphine has been earlier used in
various reactions such as conversion of alcohols to alkyl halides,14 Wittig
reaction,15 formation of thiols from aromatic disulfides,16 debromination of
a-bromoketones etc.12 The use of polymeric triphenyl phosphine offers the
advantage of simplifying the work up procedure as the polymeric phosphine
oxide can be filtered off, which otherwise interferes in the separation of the
product. Also the polymeric triphenyl phosphine is recyclable and can be
reused.
The C-alkylated of Meldrum’s acid with alcohols using triphenyl phos-
phine and N-bromosuccinimide takes place as shown in the Scheme. The
reaction has been carried out under optimised conditions with respect to the
solvent used and the stoichiometry of the reagents used. It was observed that
the reaction gave best results when carried out in acetonitrile reagents were
used in the ratio Meldrum’s acid: Ph3P: NBS ¼ 1 : 2.5 : 3.
Scheme.
The reaction of Meldrum’s acid with alcohols in presence of
triphenyl phosphine and N-bromosuccinimide under mild basic conditions
yielded C-alkylated products. It was observed that primary alcohols
gave bis-alkylated derivatives (even with the use of one equivalent of the
alcohol) whereas secondary alcohols afforded a mono-alkylated product.
1
The products were characterised by H-NMR and IR spectra. The results
of the synthesis of various C-alkylated Meldrum’s acids are reported
in Table.

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C-ALKYLATION OF MELDRUM’S ACID
Table. C-Alkylation of Meldrum’s Acid
3655
EXPERIMENTAL
Triphenyl phosphine was purchased from Aldrich Chemical Co. Inc.,
polymer supported triphenyl phosphine (2% crosslinked polystyrene with
divinyl benzene) was purchased from Fluka Co. Inc., N-bromosuccinimide

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DHURU, MOHE, AND SALUNKHE
was purchased from Spectrochem, India and was used after recrystallisation
from H2O. NMR spectra were recorded on Perkin Elmer R-32 (90 MHz)
FX-90 QFT spectrometer in CDCl3 with TMS as the internal standard.
General Procedure for the C-alkylation of Meldrum’s Acid
To a solution of triphenyl phosphine (2.5 mmol) and alcohol (2.2 mmol)
in acetonitrile (10 ml) was added N-bromosuccinimide (3.0 mmol) in small
portions with constant stirring at 0–5ꢀC. The solution was then stirred at
room temperature. Meldrum’s acid was added to the reaction mixture at
room temperature with constant stirring followed by the addition of triethyl
amine (1.4 ml). The reaction was stirred at room temperature for 2 h. After
the completion of the reaction, the reaction mixture was concentrated at
reduced pressure. Column Chromatography with chloroform : methanol
(9.8 : 0.2) yielded the pure product.
General Procedure of C-alkylation of Meldrum’s Acid
Using Polymer Supported Triphenyl Phosphine
N-Bromosuccinimide (0.60 mmol) was added with constant stirring
to the reaction mixture containing polymer supported triphenyl phosphine
(0.50 mmol,) [loading ¼ 3mmol of Ph 3P/g of resin] and alcohol (0.44 mmol)
at 0–5ꢀC. The reaction was then allowed to attain room temperature and
then Meldrum’s acid (0.2 mmol) was added at room temperature followed
by the addition of triethyl amine (0.5 ml). The reaction was then stirred at
room temperature for 1.5 h. After the completion of the reaction, the poly-
mer supported triphenyl phosphine oxide formed was filtered and washed
with 5 ml acetonitrile. The reaction mixture was concentrated at reduced
pressure. Column Chromatography with chloroform : methanol (9.8 : 0.2)
yielded the pure product.
In conclusion, this is a simple and facile method for C-alkylated
of Meldrum’s acid with advantages of simple operation, mild reaction
conditions, high yields and reuse of the polymeric species.
REFERENCES
1. Chen, B.C. Heterocycles 1991, 32, 529.
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Received in the Netherlands February 5, 2001

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