Studies on the chemistry of 5‐propynyloxy‐ and 5‐propynylthiopyrimidines: New syntheses of furo‐ and thieno[3,2‐d]pyrimidines Journal Article
| Authors: | Spada, M. R.; Klein, R. S.; Otter, B. A. |
| Article Title: | Studies on the chemistry of 5‐propynyloxy‐ and 5‐propynylthiopyrimidines: New syntheses of furo‐ and thieno[3,2‐d]pyrimidines |
| Abstract: | 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. Copyright © 1989 Journal of Heterocyclic Chemistry |
| Keywords: | unclassified drug; nonhuman; drug structure; drug synthesis; nuclear magnetic resonance; reaction analysis; infrared spectrophotometry; uracil derivative; article; furo[3,2 d]pyrimidine derivative; pyrano[3,2 d]pyrimidine derivative; thieno[3,2 d]pyrimidine derivative |
| Journal Title: | Journal of Heterocyclic Chemistry |
| Volume: | 26 |
| Issue: | 6 |
| ISSN: | 0022-152X |
| Publisher: | Wiley-Blackwell Publishing, Inc. |
| Date Published: | 1989-11-01 |
| Start Page: | 1851 |
| End Page: | 1857 |
| Language: | English |
| DOI: | 10.1002/jhet.5570260659 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 14 April 2020 -- Source: Scopus |
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