The cyclisation of benzylaminonitriles. Part 7. Regiospecific formation of methoxy-substituted isoquinolin-4-ones using methylthio activating groups

Abstract

Cyclisation of 3,4-dialkoxybenzylaminoacetonitriles proceeds preferentially through a spiro intermediate. A 2,3-dialkoxy analogue will therefore normally give a 5,6-dialkoxyisoquinolinone after rearrangement and 7,8-dimethoxy substitution is not obtained. It is shown that a suitably placed methylthio group, which can be removed after cyclisation, can change the mode of cyclisation from rearrangement via a spiro intermediate to simple ortho-attack, giving the desired 7,8-dialkoxy substitution pattern. In principle, this approach to regiocontrol could be of value in many reactions involving electrophilic attack on a benzene ring.