Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• potent and significant drugs containing imidazole moieties. The formation of imidazole derivatives can be achieved using imidazole N-oxide as starting material. In this review, the scope of substrates and reaction mechanisms of various synthetic approaches using imidazole N-oxides as substrates are

• summarized so that the chemists, researchers, and pharmaceutical industries find its effectiveness in near future for the synthesis of potent, novel, and non-toxic drug molecules. Keywords: functionalization; imidazole N-oxide; mechanistic insights; multicomponent reaction; nucleophilic substitution

• excellent works using imidazole N-oxide as starting material in recent years and the increasing number of reports proves the promising future of this field. In the past years, various excellent review papers were reported about heterocyclic N-oxides. For example, in 2014, Guobing Yan et al. published a

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

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

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• reported. It turned out that the imidazole N-oxide 7b can smoothly be converted into 1-(adamantyloxy)imidazole-2-thione 10b in the presence of 2,2,4,4-tetramethylcyclobutane-1,3-dithione (11a) as the sulfur-donating reagent. The reaction was carried out in CH2Cl2 at room temperature, and after 1 h, the

• were achieved with 7a and 7c,d. A plausible explanation of the sulfur-transfer mechanism via the intermediate [3 + 2]-cycloadduct A is presented in Scheme 5. The eliminated monothione 11b enters an analogous reaction with the starting imidazole N-oxide 7, leading to a second molecule of 10 and 2,2,4,4

• adamantylations of some benzimidazoles and imidazoles have already been reported [31], similar reactions with heterocyclic N-oxides have not been published yet. For that reason, in the final part of the study, a preliminary experiment aimed at the O-adamantylation of imidazole N-oxide 7a was carried out under

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• effects of various factors (type of acylating agents, exposure time for which the reaction mass is kept after mixing 2H-imidazole N-oxide 1 with carboranyllithium 2 and quenching with an acylating agent, as well as the temperature regime, at which the deoxygenative agent is added) have been studied. The