Thermodynamic and kinetic aspects of a single-reactor synthesis of 5-amino-3-methyl-1,2,4-triazole hydrochloride from aminoguanidine and acetic acid

Тарасова, Е. В.; Чернышев, В. М.; Chernysheva, A. V.; Abagyan, R.

doi:10.1134/s1070427211030116

Cited by 3 publications

(2 citation statements)

References 14 publications

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“… a Reference . b Reference . c Reference . d Reference . e Mean unsigned errors (MUE) and the number of outliers are also reported for each protocol. An outlier is defined as a p K a prediction deviating from the experimental value by 1.0 p K a units or more.…”

Section: Illustrative Resultsmentioning

confidence: 99%

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Bochevarov

Watson

Greenwood

et al. 2016

J. Chem. Theory Comput.

136

190

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We consider the conformational flexibility of molecules and its implications for micro- and macro-pK. The corresponding formulas are derived and discussed against the background of a comprehensive scientific and algorithmic description of the latest version of our computer program Jaguar pK, a density functional theory-based pK predictor, which is now capable of acting on multiple conformations explicitly. Jaguar pK is essentially a complex computational workflow incorporating research and technologies from the fields of cheminformatics, molecular mechanics, quantum mechanics, and implicit solvation models. The workflow also makes use of automatically applied empirical corrections which account for the systematic errors resulting from the neglect of explicit solvent interactions in the algorithm's implicit solvent model. Applications of our program to large, flexible organic molecules representing several classes of functional groups are shown, with a particular emphasis in illustrations laid on drug-like molecules. It is demonstrated that a combination of aggressive conformational search and an explicit consideration of multiple conformations nearly eliminates the dependence of results on the initially chosen conformation. In certain cases this leads to unprecedented accuracy, which is sufficient for distinguishing stereoisomers that have slightly different pK values. An application of Jaguar pK to proton sponges, the pK of which are strongly influenced by steric effects, showcases the advantages that pK predictors based on quantum mechanical calculations have over similar empirical programs.

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Section: Illustrative Resultsmentioning

confidence: 99%

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Bochevarov

Watson

Greenwood

et al. 2016

J. Chem. Theory Comput.

136

190

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show abstract

“…Precatalysts 1a , 94 1b , 95 1c , 96 1d , 97 1e , 97 1f , 98 1g , 76 and starting compounds 1-alkyl-1 H -1,2,4-triazol-3-amines ( 2a–c , g ), 88,99–105 1-unsubstituted 1 H -1,2,4-triazol-3(5)-amines ( 5b–k ), 88,99–105 4-benzyl-4 H -1,2,4-triazol-3-amines ( 7a ), 106 4-phenyl-4 H -1,2,4-triazol-3-amines ( 7b ), 107 5,7-diaryl-4,5,6,7-tetrahydro-[1,2,4]triazolo[1,5- a ]pyrimidin-2-amine ( 11a , b ) 26 and 4a′,5′,6′,7′,8′,8a’-hexahydro-4′ H -spiro[cyclohexane-1,9′-[1,2,4]triazolo[5,1- b ]quinazolin]-2′-amine ( 11c ) 108 were synthesized via procedures adapted from the literature. Other chemicals were obtained from commercial sources.…”

Section: Methodsmentioning

confidence: 99%

Selective Buchwald–Hartwig arylation ofC-amino-1,2,4-triazoles and other coordinating aminoheterocycles enabled by bulky NHC ligands and TPEDO activator

Aстахов

Chernenko

Kutyrev

et al. 2023

Inorg. Chem. Front.

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Tautomerism and basicity of carboxylic acid guanyl hydrazides (acylaminoguanidines)

et al. 2021

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Thermodynamic and kinetic aspects of a single-reactor synthesis of 5-amino-3-methyl-1,2,4-triazole hydrochloride from aminoguanidine and acetic acid

Cited by 3 publications

References 14 publications

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Selective Buchwald–Hartwig arylation ofC-amino-1,2,4-triazoles and other coordinating aminoheterocycles enabled by bulky NHC ligands and TPEDO activator

Tautomerism and basicity of carboxylic acid guanyl hydrazides (acylaminoguanidines)

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Thermodynamic and kinetic aspects of a single-reactor synthesis of 5-amino-3-methyl-1,2,4-triazole hydrochloride from aminoguanidine and acetic acid

Cited by 3 publications

References 14 publications

Multiconformation, Density Functional Theory-Based pKa Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Multiconformation, Density Functional Theory-Based pKa Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Selective Buchwald–Hartwig arylation ofC-amino-1,2,4-triazoles and other coordinating aminoheterocycles enabled by bulky NHC ligands and TPEDO activator

Tautomerism and basicity of carboxylic acid guanyl hydrazides (acylaminoguanidines)

Contact Info

Product

Resources

About

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups

Multiconformation, Density Functional Theory-Based pK_a Prediction in Application to Large, Flexible Organic Molecules with Diverse Functional Groups