Selective Debenzylation of Quaternary Salts. The Benzyl Group as an Excellent Protecting Group for Basic Nitrogen Compounds

Abstract

In several synthetic problems in our laboratory it became essential to react a basic nitrogen atom with a suitable protecting group which could be subsequently removed under very mild conditions. The presence of sensitive functionality elsewhere in the molecule prevented serious consideration of most of the reagents which have been developed for dealkylation of quaternary ammonium salts^2–12. One of the most recent methods involving the highly nucleophilic system, lithium n-propylmercaptide in hexamethylphosphoramide¹² (HMPA) was thought to be most desirable but even in this instance demethylation of the quaternary system provided difficulties. For example, demethylation of the methiodide derivative of 18β-carbomethoxycleavamine (II, R [dbnd] CH₃, 3,4-double bond) provided only a 5% yield of the desired product. It was clear that a protecting group more susceptible to nucleophilic displacement was essential. During our studies directed to this end it has been established that the benzyl group satisfies the requirements in all respects. We present some of our results since they may be of interest to others involved in research on alkaloids and other basic nitrogen compounds.