Formation of Amidinyl Radicals via Visible-Light-Promoted Reduction of N-Phenyl Amidoxime Esters and Application to the Synthesis of 2-Substituted Benzimidazoles

Abstract

We have developed a new method for the synthesis of 2-substituted benzimidazoles via amidinyl radicals generated by visible-light-promoted reduction of N-phenyl amidoxime esters in the presence of an iridium photocatalyst. This is the first report of the use of N-phenyl amidoxime esters as amidinyl radical precursors, and the first use of substituted benzene rings as amidinyl radical acceptors. This method widens the application range of substrates and overcomes the shortcomings of the traditional methods for the synthesis of 2-substituted benzimidazoles, which requires harsh reaction conditions, involves difficult-to-prepare substituted o-phenylenediamine substrates, and produces acidic waste.

Production of Amidinyl Radicals via UV–Vis-Light Promoted Reduction of N-Arylthiophene-2-carboxamidoximes and Application to the Preparation of Some New N-Arylthiophene-2-carboxamidines

“…To our delight, we prepared some new N- This may be attributed to that the amidine derivatives (2I−V) underwent intramolecular cyclization over time therein process. 31 When the starting compounds (I−V)were irradiated by UV−vis-light at different time intervals (5,10,15,20,25,35,40,55, and 60 min, respectively), they were completely consumed at 20 min. At this point, the results proved that the amidine derivatives (2I−V) represent the predominate products in the reaction.…”

“…The N-aryl-thiophene-2-carboxamidinyl derivatives radical may typically undergo intramolecular cyclization followed by dehydrogenation to afford 2-(thiophene-2-yl)benzo[d]imidazoles (1I−IV), m/e 200, 234, 214, and 230, respectively. 31,36 The hydroxyl radical may be consumed in other processes which will be shown in the next Schemes. Interestingly, this photolysis proved the facility of homolytic fission of the N−O bond for non-O-substituted amidoximes.…”

“…38 The tautomeric form of these compounds readily gives the N-arylthiophene-2-carboxamidinyl or N-arylthiophene-2-carboximidinyl radical, and then the high reactivity of amidinyl or imidinyl radicals 39,40 makes the abstraction of hydrogen from the reaction mixture more preferable. In contrast, the amidinyl radicals need high energy and longer time in the case of the formation of 2-(thiophene-2-yl)benzo[d]imidazoles (1I−IV) via the intermolecular cyclization process 41 (Scheme 1 and Table 2). All of the aforementioned reasons give us strong evidence for a highyield of the target compounds (2I−IV) when irradiated the Narylthiophene-2-carboxamidoximes (I−IV).…”

“…While the period of the reaction increased, the number of amidines decreased, and the amount of benzo­[ d ]­imidazoles ( 1I–IV ) increased. This may be attributed to that the amidine derivatives ( 2I–V ) underwent intramolecular cyclization over time therein process . When the starting compounds ( I–V )­were irradiated by UV–vis-light at different time intervals (5,10, 15, 20, 25, 35, 40, 55, and 60 min, respectively), they were completely consumed at 20 min.…”

“…The production of N -centered radicals such as iminyl and amidinyl was carried out using the cleavage of N–H, N–X, N–S, N–N, and N–O bonds (direct method) or reaction of another radical with a cyano group (indirect method) . Especially the cleavage of the N–O bond has been widely used in the formation of iminyl and amidinyl radicals via oxime and amidoxime derivatives as precursors for these radicals, according to the facility of cleavage for this bond comparatively respect with other bonds. , Zard and Wang reported that the amidinyl radicals are very important intermediates for the synthesis of imidazole and imidazoline derivatives. These versatile radicals can be generated via visible-light-promoted or electrochemistry to give several heterocycle compounds, which has many important biological applications. , …”