Synthesis 2002(1): 0043-0046
DOI: 10.1055/s-2002-19292
PAPER
© Georg Thieme Verlag Stuttgart · New York

Regioselective Synthesis of Linear and Angular Pyridazine Furocoumarins

José Carlos González-Gómez, Lourdes Santana, Eugenio Uriarte*
Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, 15782 Santiago de Compostela, Spain
Fax: +34(981)594912; e-Mail: qofuri@usc.es;
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Publikationsverlauf

Received 3 August 2001
Publikationsdatum:
04. August 2004 (online)

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.

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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.