Synthesis of some novel isocoumarins and 3,4-dihydroisocoumarins

Abstract

The work presented in this thesis consists of two parts. Part one includes general introduction, nomenclature, structural types, biosynthesis, synthesis and interconversions of isocoumarins and 3,4-dihydroisocoumarins. Pmi second is divided into two subparts. Subpart (a) includes the synthesis of naturally occuring 3-propylisocoumarin and artemidinal. 3-Propylisocoumarin was conveniently prepared in a good yield by direct condensation of homhphthalic acid with butyryl chloride. Alkaline hydrolysis of 3- propylisocoumarin yielded the corresponding keto-acid, 2-(2' -oxopentyl)benzoic acid. This keto-acid was reconverted into its respective isocoumarin by heating with acetic anhydride. (dl)-3-Propyl-3,4-dihydroisocoumarin was obtained by reduction of keto-acid to racemic hydroxy acid followed by cyclodehydration using acetic anhydride. For the synthesis of artemidinal, ethyloxalyl chloride was directly condensed with homophthalic acid to give isocumarin-3 -ethylcarboxylate. This isocoumarin was heated with hydrazine hydrate to give isocoumarin-3-acid hydrazide which on oxidation with sodium metaperiodate yielded artemidinal. Subpart (b) is concerned with the synthesis of non-naturally occurring isocoumarins including synthesis of isocoumarin derivatives of anti-inflammatory, analgesic drugs and synthesis of 3-(1 , -naphthyl) isocoumarin and conversion of the latter into(dl)-3-(1 , -naphthyl)-3 ,4-dihydroisocoumarin.3-[1 ' -( 4"-Isobutylphenyl)ethyl]isocoumarin, 3-[ l' -(5" -methoxy-2" -naphtyl)ethyl]isocoumarin,3-[ l' -(3" -flouro-4" -biphenyl)ethyl]isocoumarin and 3-(1' -propylbutyl)isocoumarin were conveniently prepared in high yield by direct condensation of acyl chlorides with homophthalic acid