Studies on the chemistry of 5-propynyloxy- and 5-propynylthiopyrimidines: New syntheses of furo- and thieno[3,2-d]pyrimidines

Autor: Brian A. Otter, Robert S. Klein, Marianne R. Spada
Rok vydání: 2009
Předmět:
Zdroj: Journal of Heterocyclic Chemistry. 26:1851-1857
ISSN: 1943-5193
0022-152X
DOI: 10.1002/jhet.5570260659
Popis: The utility of certain 5-alkynyloxy-, 5-alkynylthio, and 5-alkynylsulfinyl-pyrimidines as precursors of 7-substituted furo[3,2-d]- and thieno[3,2-d]pyrimidines has been examined. When treated with sodium methoxide in warm methyl sulfoxide, 1,3-dimethyl-5-(2-propynyloxy)uracil (6) cyclizes to afford 1,3,7-tri-methylfuro[3,2-d]pyrimidine-2,4-(1H,3H)-dione (12) in 52% yield, possibly via the allenic ether 9 (R = H). The corresponding 5-(2-butynyloxy)pyrimidine (7), obtained in good yield by treating 6 with methyl iodide and sodium hydride in methyl sulfoxide, fails to undergo an analogous cyclization. However, compound 7 does undergo a normal alkynyl Claisen rearrangement and cyclization when heated at 130°, giving the 8-methylpyrano[3,2-d]pyrimidine 8 in methyl sulfoxide and the 6,7-dimethylfuro[3,2-d]pyrimidme 11 in dimethylformamide. The 5-(2-propynylthio)pyrimidine 15 affords the allene 19 and the 1-propyne 22 when treated with various bases, but none of the 7-methylthieno[3,2-d]pyrimidine 16. At 145° in methyl sulfoxide, 15 undergoes a thio-Claisen rearrangement process to afford the 6-methylthieno[3,2-d]pyrimidine 17 together with substantial amounts of a product 20 that bears a 7-thiomethoxymethyl substituent derived from the solvent. Heating the 5-(2-propynylsulfinyl)pyriniidine 23 at 105° in methyl sulfoxide, followed by acidification of the reaction mixture, affords 1,3-dimethyl-7-formylthieno[3,2-d]pyrimidine-2,4-(1H,3H)-dione (29) in 47% yield. Deuterium labelling studies established that the aldehyde proton of 29 is derived from the 3′-proton of 23. This finding is consistent with a mechanism that involves sequential [2,3] and [3,3] sigma-tropic rearrangements, and the intermediacy of a dihydrothieno[3,2-d]pyrimidine such as compound 30.
Databáze: OpenAIRE
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