A New Synthesis of 3-Fluoroveratrole and 2-Fluoro-3, 4-Dimethoxybenzaldehyde

Abstract

In a previous paper¹ we reported the synthesis of 3-fluoro-veratrole (1) from fi-fluoroanisole via low temperature lithiation followed by reaction with trimethyl borate and peroxide oxidation followed by methylation (Scheme I). In subsequent larger scale preparations decreased yields of 1 have been observed. We have identified² 2 as the major by-product, no doubt being formed via a benzyne pathway³ which becomes more significant as reaction times become longer during 1 arger scale preparations. Therefore we required a method suitable for larger scale preparations of 1. In addition, our previous work used chloromethylation in order to introduce a carbon in to the 4-position of 1. In order to avoid this potentially hazardous reaction, we desired a method not involving chloromethylation to obtain 2-fluoro-3,4-dimethoxybenz-aldehyde (3). The methods that we have developed are shown in Scheme II.