Spirocyclic tetrahydropyrimidines derived from pentaerythritol

Abstract

A series of seven spirocyclic compounds bearing the newly synthesized 6,s-diaza-2-oxaspiro [3.5]nonane ring system are reported. Their preparation consists in the condensation of 3,3-bis(aminomethy1)oxetane n~onohydrate. obtained via pentaerythritol tribromide and, 3,3-bis(bromomethyl)oxetane, with certain amidines and guanidines.Canadian Journal of Chemistry, 46, 751 (1968) The focus of attention in the field of hypotensive drugs has been placed for some years on certain guanidines (1-3) and amidines (4) which produce their effect by preventing the release of the adrenergic transmitter substance at sympathetic nerve endings. The series of amidines and guailidiiles presented in this paper were prepared as potential sympathetic blocking agents. These constitute a departure from the recognized chemical pattern of such drugs in that the amidine or guanidiile moieties are part of a new spirocyclic structure, i.e., 6,s-diaza-2-oxaspiro[3.5]uonane. The spirocyclic compounds were obtained in five or six steps from pentaerythritol(1) according to Scheme 1.Pentaerythritol (1) was first converted into 2,2-bis(bromomethy1)-3-bromo-propanol (2) in high yields (90 %) with anhydrous hydrobromic acid in acetic acid (5). The tribromo derivative 2 was then converted to 3,3-bis(aminomethy1)-oxetane dihydrobromide as described previously (6) and as illustrated in Scheme 1. Attempts to isolate base 5 by the steam distillation method of Beyaert and Govaert (6) and by the salting out process described by Campbell (7) were unsuccessful in our hands. However, good recovery For personal use only.