A Convenient Synthesis of New 3,7-Diphenylthieno[3,2-e]bis[1,2,4] triazolo[4,3-a:4’,3’-c]pyrimidine Derivatives by Oxidative Cyclization Using Alumina-supported Calcium Hypochlorite

The heterocyclic compounds containing 1,2,4-triazole moiety continue to attract considerable interest because of their broad biological activities such as antimicrobial, antifungal, antiinflammatory, and antibacterial agents. Furthermore, it has been noticed that introduction of an additional ring to the triazolopyrimidine system which is one of the fused 1,2,4-triazole compound tends to exert profound influence in conferring new biological activities in these molecules. For instance, thienotriazolopyrimidinone 1 and pyrazolotriazolopyrimidine 2 derivatives of tricyclic heterocyclic compounds as shown in Fig. 1 have been recently synthesized for xanthine oxidase inhibitor and adenosine A2A/A3 receptor antagonists, respectively. The compound 3, 3,9-diphenyl-bis-1,2,4-triazolo[4,3-a][4’,3’-c] pyrimidine derivatives, were also found to possess strong antibacterial activity. Recently, we have designed and synthesized a series of thienotriazolopyrimidine compounds 4 and 5 of potential biological interest using iodobenzene diacetate. One of the useful methods for the preparation of fused 1,2,4triazoles is based on oxidative cyclization of the fused heterocyclic hydrazones. This oxidative cyclization has been carried out using various reagents of bromine, lead tetraacetate, phosphorus oxychloride or thionyl chloride. These reagents are often associated with several restrictions such as toxicity, poor yield, and drastic reaction conditions. In order to overcome these drawbacks, the oxidant ferric chloride, chloranil, iodobenzene diacetate and copper dichloride have been introduced. However since the reactions using reagents listed above still have some limitations, such as need of aqueous workup, use of acetic acid, separation of iodobenzene, and removal of copper ions as a water-soluble complex, the more convenient and efficient alternative reagent is required. As a continuation of our research work on thienopyrimidines and thienopyridines with biological interest, we wish to report herein the synthesis of new 3,7-diphenylthieno[3,2-e]bis [1,2,4] triazolo[4,3-a:4’,3’-c]pyrimidine derivatives 6a-h using alumina-supported calcium hypochlorite (Ca(OCl)2/Al2O3 = 1:1, grounded mixture) in oxidative cyclization reaction. The use of alumina-supported calcium hypochlorite as a heterogeneous oxidant in this reaction has advantage of enhanced reaction rate and yield, simple work-up, low cost, and eco-friendly reagent.