Cyclocondensation of oxoketene dithioacetals with 3-aminopyrazoles: a facile highly regioselective general route to substituted and fused pyrazolo a]pyrimidines
✍ Scribed by Abraham Thomas; Manjaree Chakraborty; Hiriyakkanavar Ila; Hiriyakkanavar Junjappa
- Book ID
- 104203296
- Publisher
- Elsevier Science
- Year
- 1990
- Tongue
- French
- Weight
- 745 KB
- Volume
- 46
- Category
- Article
- ISSN
- 0040-4020
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✦ Synopsis
Cyclocondensation of 3-aminopyrazole (la) and 3-amino-5-methylthio-4-phenylpyrazole (lb) withac-oxoketene dithioacetals (2a-2) derived from acyclic active methylene ketones affordF5-methylthio-6.7-substituted pyraxzo [l,5-alpyrimidines (3-d) exclusively. The reaction was found to be equally successful for the synthesis of 7-styry1,7-(4-aryl-1,3butadienyl) and 7-(6-aryl-1,3,5-hexatrienyl)pyrazolopyrimidines (7a-f) from the respective -enoylketene dithioacetals (6a-f). Similarly, the reaction of la and lb with cyclic and -benzocyclic ketene dithioacetals also afforded the angularly fused 5-methylthiopyrazolo pyrimidines regioselectively in good yields. However the oxoketene dithioacetal from cyclopentanone yielded both angularly and linearly fused regioisomers 10 and 11 respectively in nearly equal amounts. Some of the 5-methylthiopyrazolopyrimidine~were dethiomethylated with Raney nickel to afford 5-unsubstituted derivatives in good yields. Azolo[a]pyrimidines are purine analogs which are shown to be of considerable chemical 192 and pharmacological importance . The reported methods for the synthesis of these class of heterocycles usually involve cyclocondensation of aminoazoles with three carbon 1,3-electrophilic fragments such as p-ketoesters, p-diketones, P-ketoaldehydes or their enolethers and acetals3-5. However, very often these reactions result in regioisomeric mixtures of azolo[a] pyrimidines'. Besides, these methods do not offer much scope for substituent variation and structural modification because of the limited choice of B-dicarbonyl derivatives employed in these reactions. The lack of regioselectivity in these reactions appears to stem from the competitive reactivity of the 1.3-electrophilic centres in the three carbon fragments.
In principle, it should, therefore, be possible to suitably modify the electrophilic centres by appropriate functional groups so that the asymmetric binucleophiles attack preferentially only one specific electrophilic carbon atom of 3-carbon components. We recently demonstrated that the ambident binucleophile such as hydroxylamine reacts withoc-oxoketene dithioacetals to yield highly regioselective either 5-methylthio or 3-methylthioisoxazoles depending on the pH conditions of the reaction medium6. It was therefore considered that the reactivity of=-oxoketene dithioacetals with aminoazoles might result in improved regioselectivity yielding only one regioisomer under a particular reaction condition. We have examined this regioselectivity through the reaction of 3-aminopyrazoles witho(-oxoketene dithioacetals,