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Synthesis 2010(23): 4021-4032  
DOI: 10.1055/s-0030-1258292
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Green Approach to the Synthesis of Fused Uracils: Pyrano[2,3-d]pyrimidines. ‘On-Water’ One-Pot Synthesis by Domino Knoevenagel/Diels-Alder Reactions

Aleksandra Pałasz*
Department of Organic Chemistry, Jagiellonian University, ul. Ingardena 3, 30-060 Kraków, Poland
Fax: +48(12)6340515; e-Mail: palasz@chemia.uj.edu.pl;
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Publikationsverlauf

Received 29 May 2010
Publikationsdatum:
12. Oktober 2010 (online)

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Abstract

‘On-water’ Knoevenagel condensations of 2-thiobarbituric acid and N,N-dimethylbarbituric acid with aromatic and heteroaromatic aldehydes were carried out without a catalyst and at room temperature. Condensations in aqueous suspensions occurred rapidly, giving excellent yields. Solvent-free hetero-Diels-Alder reactions of 5-arylidene derivatives of barbituric acids with ethyl vinyl ether were investigated at room temperature and pyrano[2,3-d]pyrimidines of potential pharmacological activity were obtained in excellent yields. Three-component one-pot syntheses of annulated uracils were performed in aqueous suspensions. Reactions of barbituric acids, aldehydes, and ethyl vinyl ether were carried out at ambient temperature, whereas the one-pot synthesis with barbituric acids, aldehydes, and styrene or N-vinyl-2-oxazolidinone required the heating of aqueous suspensions at 60 ˚C. ‘On-water’ cycloadditions were characterized by high diastereoselectivity in contrast to reactions carried out in homogeneous organic media (dichloromethane, toluene). They allowed the cis adducts to be obtained preferentially or exclusively. The presented green methods avoid the use of catalysts, the heating of reaction mixtures for long times at high temperatures, and the use of organic solvents, and make the synthesis of a variety of pyrano[2,3-d]pyrimidines chemically efficient. The results reveal water as the medium of choice for the examined cycloadditions.

Key words

Diels-Alder reactions - drugs - green chemistry - pyrano[2,3-d]pyrimidines - solvent effects