V. Osyanin, D. Osipov, S. A. Pavlov
Oct 8, 2014
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Influential Citations
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Chemistry of Heterocyclic Compounds
Abstract
Naphthoand benzopyranopyrimidines are important heterocycles in pharmaceutical chemistry. They include compounds having antibacterial and fungicidal activity [1] as well as behaving as antagonists of the neuropeptide S receptor [2] and showing antiallergic properties [3]. In general, 1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones unsubstituted at position 5 or containing an aryl substituent are prepared by reduction of 2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones [3-7] or the corresponding pyrilium salts [8], through the cyclization of certain barbituric acid derivatives [3], or by hightemperature condensation of salicyl alcohol with 6-chlorouracil [7, 9]. In addition, the electron-rich 3,4-methylenedioxyphenol can be used in a three-component condensation with barbituric acid and aromatic aldehydes [10-13]. At the same time, existing methods of synthesis generally preclude the preparation of 1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2,4(3H)-diones substituted at a nitrogen atom or are limited to single examples. We have proposed a novel method for the synthesis of 1,5-dihydro-2H-chromeno[2,3-d]pyrimidine2,4(3H)-diones 3a-f from 6-amino-1,3-dimethyluracil (1) and the o-benzoquinone methide precursors, namely, o-hydroxybenzyl alcohols 2a-d, Mannich base 2e, and quaternary ammonium salt 2f. The reactions were carried out by refluxing an equimolar mixture of the reagents for 5-10 h in acetic acid. A single recrystallization gave chromatographically pure materials in 38-85% yields. The low yield of chromenopyrimidine 3f is apparently due to the ready oligomerization of the corresponding sterically unshielded o-quinone methide.