title: Reactivity of C-Amino-1,2,4-triazoles toward Electrophiles: A Combined Computational and Experimental Study of Alkylation by Halogen Alkanes.
abstract: A combination of computational and experimental methods was used to examine the structure-reactivity relationships in the reactions of C-amino-1H-1,2,4-triazoles with electrophiles. The global nucleophilicity of 3-amino- and 3,5-diamino-1H-1,2,4-triazoles was predicted to be higher than that of 5-amino-1H-1,2,4-triazoles. Fukui functions and molecular electrostatic potential indicate that reactions involving an amino group should occur more easily for the 3-amino- than for the 5-amino-1H-1,2,4-triazoles. Increasing electrophile hardness should increase the probability of attack at the N-4 atom of the triazole ring, whereas increasing softness should enhance the probability of attack at the N-2 atom and 3-NH2 group. Calculated transition state energies of model SN2 reactions and experimental studies showed that quaternization of 1-substituted 3-amino- and 3,5-diamino-1H-1,2,4-triazoles by many alkyl halides proceeds with low selectivity and can involve the N-2 and N-4 atoms as well as the 3-NH2 group as reaction centers. A new method for the selective synthesis of 1,4-disubstituted 3-amino- and 3,5-diamino-1,2,4-triazoles based on quaternization of readily available 1-substituted 3-acetylamino-1,2,4-triazoles with subsequent removal of the acetyl protecting group by acid hydrolysis was developed.
authors.affiliation: †Platov South-Russian State Polytechnic University (NPI), Prosveschenya 132, 346428 Novocherkassk, Russian Federation.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Chernyshev
authors.affiliation: †Platov South-Russian State Polytechnic University (NPI), Prosveschenya 132, 346428 Novocherkassk, Russian Federation.
authors.forename: Anna G
authors.initials: AG
authors.lastname: Vlasova
authors.affiliation: †Platov South-Russian State Polytechnic University (NPI), Prosveschenya 132, 346428 Novocherkassk, Russian Federation.
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Astakhov
authors.affiliation: ‡State Scientific Institution "Institute for Single Crystals" of National Academy of Sciences of Ukraine, Lenin Ave. 60, 61001 Kharkiv, Ukraine.
authors.forename: Svitlana V
authors.initials: SV
authors.lastname: Shishkina
authors.affiliation: ‡State Scientific Institution "Institute for Single Crystals" of National Academy of Sciences of Ukraine, Lenin Ave. 60, 61001 Kharkiv, Ukraine.|§V. N. Karazin Kharkiv National University, 4 Svobody sq., Kharkiv 61202, Ukraine.
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Shishkin
mesh_terms: D000478:Alkylation; D006846:Hydrocarbons, Halogenated / Q000737:chemistry*; D015394:Molecular Structure; D011789:Quantum Theory; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D006846:Hydrocarbons, Halogenated; D014230:Triazoles; C045575:1,2,4-triazole