New syntheses of dillapiol [4,5-dimethoxy-6-(2-propenyl)-1,3-benzodioxole], its 4-methylthio and other analogs

Three syntheses of the natural synergist dillapiol from the natural, commer cially available sesamol as starting material, are described. A major diffe rence between these is the order of introduction of the additional methoxy and allyl substituents. In one of the syntheses, a formyl group is introduc ed at C4 via an electrophilic aromatic substitution reaction and then conve rted into the methoxy group using a Baeyer-Villiger reaction and subsequent methylation; in the other two, a directed ortho-metalation, Baeyer-Villige r, methylation sequence was employed. Various intermediates along the synth etic route were used to generate more than 30 analogs, including the 4-thio methyldillapiol, to investigate the structure activity relationships of the pesticide synergism of these compounds. Radio-labeled dillapiol, bearing C -14 at the C4 methoxy group was also prepared. Initial screening with mosqu ito larvae showed that most of the derivatives prepared in this study had s ignifacant synergistic activities in combination with the phototoxic larvic ide alpha -therthiophene.