153478-97-8Relevant articles and documents
Reactions of Azolium Cations. II. Regioselective N2 Alkylation of 5-Aryltetrazoles with Isopropyl Alcohol in Sulfuric Acid Media: Effect of Electronic Properties of Aryl Substituents on the Reaction Rate
Koren, A. O.,Gaponik, P. N.,Ostrovskii, V. A.
, p. 919 - 924 (1995)
Kinetics of regioselective N2 alkylation of a series of 5-(R-phenyl)tetrazoles with isopropyl alcohol has been studied in 88.2, 94.3, and 98.3percent (w/w) sulfuric acid at 25 deg.The true rate constants were evaluated, logarithms of which were found to correlate with ?0 constants of phenyl substituents as log k = -0.488?0 - 0.417.Small value of Hammett constant ρ is evidence of a considerable isolation of the reaction center from the influence of the substituent at position C5 of the heteroring.This conclusion is confirmed by results of MNDO quantum chemical calculations of a series of 5-substituted tetrazolium cations.A correlation between logarithms of the true rate constants and the calculated net effective charges on atoms N2(N3) for 5-(R-phenyl)tetrazolium cations has been revealed.
Alkylation of 5-Substituted 1 H-Tetrazoles via the Diazotization of Aliphatic Amines
Lebel, Hélène,Reynard, Guillaume
, p. 12452 - 12459 (2021/09/07)
A new alkylation reaction of monosubstituted tetrazoles via the diazotization of aliphatic amines is reported. This method enables preferential formation of 2,5-disubstituted tetrazoles. A one-pot 1,3-dipolar cycloaddition/diazotization sequence starting from widely available nitriles is also described. Azide residues are quenched in the second step with the nitrite reagent, thus limiting the intrinsic risk associated with trimethylsilyl azide. The reaction conditions were compatible with several functional groups, including thiocyanates, which afford preferentially disubstituted 2-alkyl-5-(substituted-thio)tetrazoles.
Regio- and Enantioselective Synthesis of Azole Hemiaminal Esters by Lewis Base Catalyzed Dynamic Kinetic Resolution
Piotrowski, David W.,Kamlet, Adam S.,Dechert-Schmitt, Anne-Marie R.,Yan, Jiangli,Brandt, Thomas A.,Xiao, Jun,Wei, Liuqing,Barrila, Mark T.
supporting information, p. 4818 - 4823 (2016/05/09)
We report a modular three-component dynamic kinetic resolution (DKR) that affords enantiomerically enriched hemiaminal esters derived from azoles and aldehydes. The novel and scalable reaction can be used to synthesize valuable substituted azoles in a regioselective manner by capping (e.g., acylation) of the equilibrating azole-aldehyde adduct. With the use of a prolinol-derived DMAP catalyst as the chiral Lewis base, the products can be obtained in high chemical yield and with high enantiomeric excess. The DKR was performed on a multikilogram scale to produce a tetrazole prodrug fragment for a leading clinical candidate that posed formidable synthesis challenges.
Alkylation of 5-substituted NH-tetrazoles by alcohols in the superacid CF3SO3H
Lisakova, Anna D.,Ryabukhin, Dmitry S.,Trifonov, Rostislav E.,Ostrovskii, Vladimir A.,Vasilyev, Aleksander V.
supporting information, p. 7020 - 7023 (2015/11/27)
Reactions of 5-substituted NH-tetrazoles with alcohols in the superacid CF3SO3H have been studied. Both the structure of the tetrazole and the nature of alcohol were found to dramatically influence the selectivity of the reaction and yields of products. Tetrazoles bearing phenyl, electron-donating aryl, or benzyl groups at the 5-position, have been alkylated using various alcohols (including MeOH and EtOH) in CF3SO3H upon heating at 60 °C for 0.3-12 h to afford 2-alkyl-2H-tetrazoles in 30-98% yields.
