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

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.

2-Unsubstituted Imidazole N-Oxides as Novel Precursors of Chiral 3-Alkoxyimidazol-2-ylidenes Derived from trans-1,2-Diaminocyclohexane and Other Chiral Amino Compounds

“…Enantiomerically pure, ( R , R )-configured 2-unsubstituted imidazole N -oxides 6 used in this study as the key building blocks were prepared from enantiopure formaldimines 4 , derived from the corresponding amines 1 , and α-hydroxyiminoketones 5a , b in glacial acetic acid at room temperature [24]. In the case of 4b , along with the ( R , R )-configured stereoisomer, the ( S , S )-enantiomer was also involved in the study (Scheme 5 and Table 1).…”

“…The obtained crude imidazolium salts 7 were used as precursors of chiral imidazol-2-ylidenes 8 (Scheme 6). Their intermediacy was proven with known trapping reactions with elemental sulfur [24,29,30] leading to non-enolizable imidazole-2-thiones. The deprotonation of 7 was easily achieved by treatment with triethylamine in pyridine.…”

“…However, these 1-alkoxyimidazolium salts have never been used for the generation of N -alkoxy-substituted imidazol-2-ylidenes of type 3 . In a very recent publication, we reported the synthesis of non-symmetric imidazolium salts prepared in a multistep synthesis starting with adamantyloxyamine [24]. In a test experiment, a symmetric 1,3-di(adamantyloxy)imidazolium salt was converted into the corresponding imidazole-2-thione derivative via an intermediate NHC.…”

Synthesis, Selected Transformations, and Biological Activity of Alkoxy Analogues of Lepidilines A and C

“…103–106 °C (m.p. 104–106 °C [ 17 ]). 1 H-NMR (CDCl 3 , 600 MHz): δ 1.59, 1.70 (2 d br , J ≈ 12.3 Hz, 6 H, Ad), 1.86 (m c , 6 H, Ad), 2.16, 2.20 (2 s, 3 H each, 2 Me), 2.27 (m c , 3 H, Ad), 7.85 (s, 1 H, C(2)H) ppm.…”

“…In more recent publications by our group, straightforward protocols for the synthesis of alkoxy-functionalized imidazolium salts, as well as their applications for generation of the corresponding N-alkoxyimidazol-2-ylidenes, were demonstrated [17,18]. In these studies, the respective 2-unsubstituted imidazole N-oxides served as convenient substrates.…”