Regioselective Synthesis of Linear and Angular Pyridazine Furocoumarins

Abstract

With a view to develop a general regioselective route to pyridazine analogues of benzofurocoumarins, the angular compound 3 and the linear compound 9 were synthesized. In both cases the key step in the construction of the fused pyridazine ring was a Diels-Alder reaction of the intermediate dihydrofura-3-ones with 3,6-bis(trifluoromethyl)-1,2,4,5-tetrazine. The furocoumarinone precursor 2 of compound 3 was synthesized in 60% yield by regioselective Fries rearrangement of 7-(chloroacetyloxy)coumarin (1). The benzofuranone 7, the precursor of compound 9, was obtained in a preparatively useful scale and 34% overall yield from ethyl 2,4-dimethoxycinnamate (4) in 3 steps by regioselective Friedel-Crafts chloroacetylation and further cyclization. The coumarin skeleton of compound 9 was completed in the final step by lactonization with BBr₃.

Key words

Diels-Alder reactions - electrophilic aromatic substitutions - polycycles - heterocycles - regioselectivity

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19

Attempts to improve the acylation yield under classical Friedel-Crafts conditions,^20,21 using 1-3 equiv of chloroacetyl chloride in refluxing CS₂ or CCl₄ and 2 equiv of AlCl₃, afforded intractable black tars.