SYNTHESIS AND POLYMERIZATION OF ANTI-BREDT, NITROGEN-BRIDGEHEAD BICYCLIC URETHANES

Abstract

Three nitrogen-bridgehead, bicyclic urethanes, 1-aza-8-oxa-bicyclo[4.3.0]nonan-9-one, I, 1-aza-3-oxabicyclo[3.3.1]nonan-2-one, II, and 1-aza-6-oxabicyclo[3.2.1]octan-7-one, III, were synthesized. UNFORMATTED TABLE OR EQUATION OMITTED - PLEASE SEE DISSERTATION. Contrary to popular opinion and in formal disagreement with Bredt's Rule, conformationally strain-free bicyclic urethanes II and III are stable because of N-C=O -O resonance interaction. The demand of the carbonyl for electrons is satisfied by N and O atoms. Urethane II was synthesized by cyclization of 3-chloroformyloxymethylpiperidine hydrotosylate using triethylamine or by refluxing 3-hydroxymethylpiperidinocarbamoyl chloride with excess triethylamine. To satisfy the N-C = 0 and O-C = 0 electron donation, the molecule does not exist in the two-chair form other [3.3.1] systems do, but in a form between the two-chair, boat-chair and flat-chair forms. Its low carbonyl stretching frequency, resistance to hydrolysis and resistance to ring-opening polymerization, all show that the molecule is not strained. 1-Aza-6-oxabicyclo[3.2.1]octan-7-one, III, was synthesized by the reaction of 3-hydroxypiperidinocarbamoyl chloride with four equivalents of triethylamine. It absorbed at 1770 cm⁻¹, 20 cm⁻¹ higher than Ḭ. Water hydrolyzed it at room temperature and phosphoric acid polymerized it at 105°, but it resisted ring-opening polymerization by potassium t-butoxide and p-toluenesulfonic acid in DMSO. As a reference, Ḭ was synthesized in five ways. It was obtained by the action of triethylamine on 2-chloroformyloxymethylpiperidine hydrostosylate, by reacting a mixture of triethylamine. phosgene and 2-hydroxymethylpiperidine, and by refluxing ethylene carbonate, diphenylcarbonate or di-t-butyl tricarbonate with 2-hydroxymethylpiperidine. Urethane I was stable in boiling water for 24 hr, and aqueous sodium hydroxide for two days. It showed no signs of polymerization after heating for extended periods with p-toluenesulfonic acid, phosphoric acid or potassium t-butoxide. The rearrangements of chloroformyloxypiperidines to hydroxypiperidinocarbamoyl chlorides were performed, and unsuccessful attempts were made to synthesize 1-aza-3-oxabicyclo[2.2.2]nonan-2-one.