Understanding the regioselectivity of 5-substituted 1H-tetrazoles alkylation

Abstract

The synthesis of disubstituted tetrazoles is described from 1H-5-monosubstituted tetrazoles via the aliphatic amine diazotization reaction, which forms a transient alkyl diazonium intermediate, acting as an alkylating agent. Although the...

Sequential, Electrochemical‐Photochemical Synthesis of 1,2,4‐Triazolo‐[4,3‐a]pyrazines

“…Once the suitable electrolysis reaction conditions were determined using our model system, they were then applied to various tetrazole species ( 11 a – q ) and high nitrogen heterocycles ( 10 a’ – o’ ) (Scheme 3). Although 5H tetrazole was used as the model tetrazole species for reaction optimization, we chose 5‐bromotetrazole ( 11 b ) for future coupling reactions with 10 a’ – o’ due to its ease of synthesis that avoids highly dangerous hydrazoic acid, its more sterically hindered and electronically deactivated N 1 site and its potential for further downstream functionalization afforded by halogen substitution reactions [47,48] . Additionally, 5‐bromoterazole proved advantageous for the detection of coupled materials via LC–MS analysis due to the characteristic M/Z signature resulting from the isotopic nature of bromine.…”

“…Although 5H tetrazole was used as the model tetrazole species for reaction optimization, we chose 5-bromotetrazole (11 b) for future coupling reactions with 10 a'-o' due to its ease of synthesis that avoids highly dangerous hydrazoic acid, its more sterically hindered and electronically deactivated N1 site and its potential for further downstream functionalization afforded by halogen substitution reactions. [47,48] Additionally, 5-bromoterazole proved advantageous for the detection of coupled materials via LC-MS analysis due to the characteristic M/Z signature resulting from the isotopic nature of bromine. Lastly, 5-bromotetrazole was found to couple with heterocycles that 5H tetrazole failed to show coupling (e. g., 2-quinoxalinol, 2-methoxypyrazine, and 2-chloro-6-methoxy pyrazine).…”