Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts.

Katarzyna Urbaniak,Grzegorz Mlostoń,Heinz Heimgartner,Vladyslav Bakhonsky,Peter R Schreiner,Małgorzata Celeda,Marcin Jasiński

doi:10.3762/bjoc.15.43

Abstract

Adamantyloxyamine reacts with formaldehyde to give N-(adamantyloxy)formaldimine as a room-temperature-stable compound that exists in solution in monomeric form. This product was used for reactions with α-hydroxyiminoketones leading to a new class of 2-unsubstituted imidazole 3-oxides bearing the adamantyloxy substituent at N(1). Their reactions with 2,2,4,4-tetramethylcyclobutane-1,3-dithione or with acetic acid anhydride occurred analogously to those of 1-alkylimidazole 3-oxides to give imidazol-2-thiones and imidazol-2-ones, respectively. Treatment of 1-(adamantyloxy)imidazole 3-oxides with Raney-Ni afforded the corresponding imidazole derivatives without cleavage of the N(1)–O bond. Finally, the O-alkylation reactions of the new imidazole N-oxides with 1-bromopentane or 1-bromododecane open access to diversely substituted, non-symmetric 1,3-dialkoxyimidazolium salts. Adamantyloxyamine reacts with glyoxal and formaldehyde in the presence of hydrobromic acid yielding symmetric 1,3-di(adamantyloxy)-1H-imidazolium bromide in good yield. Deprotonation of the latter with triethylamine in the presence of elemental sulfur allows the in situ generation of the corresponding imidazol-2-ylidene, which traps elemental sulfur yielding a 1,3-dihydro-2H-imidazole-2-thione as the final product.

Highlights

Imidazole N-oxides constitute a practically valuable class of five-membered aromatic N-heterocycles [1,2,3,4,5]
The crude product was reacted with formaldehyde in boiling MeOH, and after 1 h, crystalline N-(adamantyloxy)formaldimine (6a) was isolated in 90% yield
The present study demonstrates that the heterocyclization reaction with α-hydroxyiminoketones and formaldimines leading to 2-unsubstituted imidazole 3-oxides can efficiently be performed with N-(adamantyloxy)formaldimine, and 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides were obtained in high yields

Summary

Introduction

Imidazole N-oxides constitute a practically valuable class of five-membered aromatic N-heterocycles [1,2,3,4,5]. The subclass of 2-unsubstituted imidazole N-oxides 1 with diverse substituents located at N(1), C(4), and C(5) is of special interest as so-called ‘nitrone like’ reagents for the synthesis of more complex, imidazole containing systems (Scheme 1) [6]. Scheme 1: Synthesis of 2-unsubstituted imidazole N-oxides 1 from α-hydroxyiminoketones 2 and formaldimines 3

Objectives

Results

Conclusion