Synthesis and Dimroth Rearrangement of 6-Cyano-l,2,4-triazolo- [4,3-a]pyrimidin-5- and 7-ones. A Novel Alkylation with Orthoesters and a New Participation of the Cyano Group in the Rearrangement

Abstract

The cyclization products of 5-cyano-2-hydrazino-6-phenyl-3,4-dihydropyrimidin-4-one (6) with one carbon inserting agents have been confirmed to be of the l,2,4-triazolo[4,3-a]pyrimidin-5(8//)-ones type and not the respective 7-ones, by comparing their alkylated deriva tives 10a, 11a, 27 and 28 with the product from the cyclization of the 3-methyl and 3-benzyl derivatives of 6. A novel alkylation process was found when triethyl orthoformate was used as a cyclizing agent. Dimroth rearrangement of 8, 14, 15, 24, 34 and 36 with 2% ethanolic KOH gave the respective triazolo[l,5-a]pyrimidinone 13, 18, 19, 25, 38 and 40, respectively. Using 10% ethanolic KOH led to a novel participation of the cyano group in the rearrange ment whereby 8a gave 7-imino-5-phenyl-l,2,4-triazolo[l,5-a]pyrimidine 22.

Facile entries for regioselective synthesis of [1,2,4]triazolo-[4,3-a]pyrimidin-5(1H)-ones from 2-thiouracil

“…The first step involves acylation of 2 with 3 to give N3-hydrazonoyl derivative 4 rather than N1-substituted analog 5. This site selectivity is similar to that found for alkylation and acylation reactions of 2-methylthiopyrimidin-4(3H)-ones which were reported to occur at N3 rather than N1 [3,14,15]. This is because the tautomeric of 2-alkylthiouracils were reported to exist in the 3H-form rather than the 1H-form [16].…”

“…At present, the general synthetic strategy for such compounds depends on cyclization of the appropriate 2-hydrazinopyrimidines with one carbon inserting agents [2,3]. The starting 2-hydrazinopyrimidines are usually prepared by nucleophilic displacement of the SH or MeS group at C-2 of the respective 2-thiouracil derivatives [3]. The interest in the synthesis of derivatives of such ring system is due to that many of them were reported to possess a wide range of pharmacological activities [2].…”

A facile one‐pot regioselective synthesis of [1,2,4]triazolo[4,3‐a]5(1H)‐pyrimidinones via tandem Japp–Klingemann, Smiles rearrangement, and cyclization reactions

“…The spectral and analytical data were unexpectedly consistent with either of the two isomeric [1,2,4]triazolopyrimidines 7 or 8 (Scheme 1). Distinction between these two structures was made on the basis of the 13 C NMR and IR spectra. Literature reports [11] have shown that the chemical shift for the carbonyl carbon in 4-pyrimidinone derivatives is markedly affected by the nature of the adjacent nitrogen (pyridine type in our structure 8 and pyrrole type in our structure 7).…”

“…Thus, treatment of 10 with 9, in ethanol, in the presence of sodium ethoxide, under reflux, was found to give products proved to be identical in all respects with products 7 obtained above. As both alkylation and acylation of 2-alkylthiouracil usually occur at N3 rather than N1 [13], it is not unreasonable to assume that reaction of 10 with 9 proceeds via the formation of the amidrazones 11, which, in turn, undergo cyclization with elimination of methanethiol to give 7 as end products (Scheme 2).…”

Tandem in situ generation and 1,5-electrocyclization of N-hetaryl nitrilimines. A facile methodology for synthesis of annulated 1,2,4-triazoles and their acyclo C-nucleosides

“…However, similar treatment of the hydrazones 60 with Br 2 /AcOH was reported to give the Dimroth rearrangement products 62 directly as end product. 106 On the other hand, the cyclization of 60 with thionyl chloride gave 61 as the major isolated products. Partial Dimroth rearrangement has taken place during this cyclization, where 62 were formed as by products.…”