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
