Synthesis and isomerization of thienotriazolopyrimidine and thienotetrazolopyrimidine derivatives with potential anti-inflammatory activity

Abstract

Several derivatives containing the thieno [2,3-d]pyrimidine system were prepared starting from 2-amino-4,5-dihydronaphtho[2,1-b]thiophene-1-carbonitrile (1). In particular, the synthesis and structure characterization of 8,9-dihydronaphtho-[1 ,2 :4,5]thieno [3,2-e] [1,2,4]triazolo [4,3-c]pyrimidine derivatives 13-16 and their isomerization to 8,9-dihydronaphtho[1 ,2 :4,5]thieno [3,2-e]

Synthesis and Isomerization of Some Novel Pyrazolopyrimidine and Pyrazolotriazolopyrimidine Derivatives

“…However, the (Table 1). These data are in agreement with reported results of related compounds [15][16][17][18]21,22,24] and confirmed that the product obtained from the reaction with hydrazino derivative 3 differ than those obtained from the reaction with imino derivative 2. …”

“…Compound 2 was isomerized to its corresponding more thermodynamically stable 4-hydrazino derivative 3 upon refluxing in dioxane in the presence of a few drops of piperdine. Actually, piperdine acts as a base in this Dimroth-type rearrangement which involves a sequence of ring opening and ring closure reactions (Scheme 2) [15,20,21].…”

“…Previous observations revealed that the [1,2,4]triazolo [4,3-c]pyrimidine derivatives can isomerize under different suitable reaction conditions to the thermodynamically more stable [1,2,4]triazolo [1,5-c]pyrimidines [14][15][16]. This isomerization was first reported by Miller and Rose [17,18] when they treated [1,2,4] triazolo [4,3-c]pyrimidine derivatives with an acid, base, or thermally.…”

“…Ar` = Ar` = However, when compound 3 was heated under reflux in acetic acid, it afforded compound 6, probably via the intermediacy of its [1,2,4]triazolo [4,3-c]pyrimidine isomer 7 which was not isolated in this reaction, but rather underwent a Dimroth-type rearrangement [15,20] under the reaction conditions. To prove this assumption, compound 7 was converted into its corresponding [1,2,4] triazolo [1,5-c]pyrimidine derivative 6 by heating in ethanol in the presence of few drops of glacial acetic acid (Scheme 3).…”

Synthesis of Pyrimidines and Heteroannulated Pyrimidine Ring Systems

“…From the 1 H NMR spectrum, the product was obtained as a pair of isomers (7 and 7a) (77:23) presumably as a result of Dimroth-type rearrangement. [10][11][12] As mentioned, the reaction was subjected to conditions which strongly favour formation of the thermodynamically more stable isomer (strong base and heat for long time) which could enhance the isomerization to give only one isomer but still the two isomers were seen; hence this should be the thermodynamic mixture. It worth to mention that the structure 7 was probably the major isomer, this is based on the fact that it is more conjugated and looks like a tetraene; on the other hand structure 7a looks like a triene.…”