Synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl) propanamides and their tautomerism (original) (raw)
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A microwave-assisted synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides from succinimides
Proceedings of The 21st International Electronic Conference on Synthetic Organic Chemistry, 2017
1,2,4-Triazole is a privileged scaffold in medicinal and agricultural chemistry. Many useful and structurally diverse compounds have been prepared using 5-amino-1,2,4-triazoles as building block. Herein, we report a new microwave-assisted synthesis of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides via two complementary approaches. The first approach involved the initial preparation of N-guanidinosuccinimide, which then reacted with amines under microwave irradiation affording corresponding 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides. The desired products were successfully obtained in the reaction with aliphatic amines (primary and secondary) via a nucleophilic opening of the succinimide ring and the subsequent recyclization affording the 1,2,4-triazole ring. This approach failed when less nucleophilic aromatic amines were used. Therefore, we designed an alternative pathway with the initial preparation of N-arylsuccinimides and their subsequent reaction with aminoguanidine hydrochloride under microwave irradiation. In this case, the 1,2,4-triazole ring closure was most efficiently achieved in the presence of organic base. These two approaches complement each other allowing preparation of a diverse library of 3-(5-amino-1H-1,2,4-triazol-3-yl)propanamides.
An aqueous medium synthesis and tautomerism study of 3 (5)-amino-1, 2, 4-triazoles
Tetrahedron Letters, 2009
A catalyst-free highly efficient synthesis of 3(5)-amino-5(3)-(het)aryl-1,2,4-triazoles in aqueous medium was performed using conventional heating and microwave irradiation. The tautomerism in the products was investigated using NMR spectroscopy and X-ray crystallography. The effects of the substitution, temperature, solvents, and concentration on the tautomerism were studied. The triazoles were found to exist in 1H-forms, the 4H-form was not observed either in solid state or in solution. In general, 5-amino-1,2,4-triazoles were electronically preferred in the tautomeric equilibrium, but some exceptions from the established relationship were also identified.
The Journal of Engineering and Exact Sciences
The condensation reaction between aminoguanidine bicarbonate with carboxylic acids led to the formation of 3-methyl-1H-1,2,4-triazole-5-amine (mta), 3-methyl-1H-1,2,4l4-triazole-5-amine acetate (Hmta) and 3-phenyl-1H-1,2,4-triazole-5-amine (pta). The compound N-(3-methyl-1H-1,2,4-triazole-5-yl)propan-2-imine (mpta) was obtained by reacting the mta with acetone, upon an attempt of purifying mta in this solvent. The excess of acetic acid obtained the Hmta during the preparation of mta. These compounds were characterised by infrared and multinuclear NMR (1H and 13C) spectroscopy, microanalysis, and melting point. To investigate the formation of possible tautomeric conformations of mta, pta and mpta in solution, a theoretical approach was used to calculate the chemical shifts of carbon 13, based on the values of magnetic shielding tensor (NMR) by MPn and DFT methods. The biological assay of the triazoles mta, pta and mpta against Staphylococcus aureus, Bacillus subtilis, Escherichia col...
A new simple and efficient approach to 2,4-disubstituted 1,2,3-triazoles-5-amines from the reaction of 2-arylhydrazononitriles and hydroxylamine is described. Investigation of behavior of 3-phenyl-3oxo-2-arylhydrazonopropane nitriles has been undertaken. In addition to readily reported formation of aminoisoxazoles, 4-benzoyl-1-aryl-1,2,3-triazole-5-amines 5f,g were prepared via cyclising products of reacting 2f,g with hydroxylamine in basic medium.
In the present study, the interaction of 4-(N-substituted)-3-pyridyl-5-mercapto-s-triazole with secondary amines was explored. The Isonicotinic acid hydrazide was converted into the corresponding potassium dithiocarbazinate, by reacting with carbon disulphide in alkaline medium which undergoes ring closure reaction after further treatment with aqueous potassium hydroxide to give 5-pyridyl-2-mercapto-1,3,4-oxadiazole. 4-(N-pyridylcarboxamido)-3-pyridyl-5-mercapto-s-triazole and 3-pyridyl-4-amino-5-mercapto-s-triazole were obtained in one pot reaction by heating equimolar quantities of oxadiazole with isonicotinic acid hydrazide and hydrazine hydrate respectively. Condensation of triazole with secondary amines in anhydrous dimethyl sulfoxide results in the formation of corresponding quaternary salts. The synthesized compounds were confirmed by IR, 1 HNMR spectra and elemental analysis. All the compounds were screened for their preliminary in-vitro antibacterial and antifungal activity.
Multicomponent reactions involving polyfunctional 4-amino-5-carboxamido-1,2,3-triazole and cyclic carbonyl-containing CH-acids were studied under conventional thermal heating, microwave and ultrasonic irradiation. The features of the reactions studied were discussed and the optimized procedures for the synthesis of final triazolopyrimidines were elaborated. In contrast to the similar MCRs of numerous other aminoazoles, a change of direction of the heterocyclizations in the case of 4-amino-5-carboxamido-1,2,3-triazole was not observed when microwave or thermal heating was substituted by ultrasonication at ambient temperature.
Amino acids as building blocks for the synthesis of substituted 1,2,4-triazoles
Tetrahedron, 2011
We report on the synthesis of 1,2,4-triazoles substituted with 2 or 3 amino acid side chains, using silver benzoate as a key reagent for the cyclization step. A complete study of the optical purity retention during the synthetic process leading to these compounds is described. In addition an improved work-up after the addition-cyclization step was also established leading to better yields and metal-free products.
Synthesis of chiral α-amino acid-derived 1H-1,2,4-triazoles and 1,2,4-triazines
MedChemComm, 2012
Enantiopure N-(Cbz, Fmoc, Boc, or Ac)-1H-1,2,4-triazole-(8a-p, and 8f 0 ) and previously unknown N-Cbz-1,2,4-triazine-derived a-amino acids (11a-d, 11d 0 , 13a,b, and 13a 0 ) were synthesized using microwave irradiation. Reaction conditions led unexpectedly to simultaneous cyclization, deprotection and acetylation of N-Boc-aminoacylamidrazones 7m,n to afford N-acetyl-1H-1,2,4-triazoles 8o,p.
Vìsnik farmacìï, 2015
The synthesis of a series of new 4-amino-5-alkyl-1,2,4-triazole(4H)-3-yl thioacetanilides and 4-pyrrolyl-5-alkyl-1,2,4-triazole(4H)-3-yl thioacetanilides has been described in the article. The key intermediates-4-amino-5-alkyl-3-mercapto-1,2,4-triazoles(4H) 4a-c were synthesized started from the corresponding carboxylic acids (acetic, propanoic and butanoic) after their esterification followed by hydrazinolysis, CS 2 reaction and cyclisation under hydrazine hydrate. The first group of substances 6a-p was obtained by alkylation of the key intermediate 4a-c with chloroacetic acid anilides in the presence of basic catalysts. The subsequent modification under conditions of Paal-Knorr reaction led to the corresponding pyrrolyl derivatives 7a-p. The structure of the compounds synthesized has been proven by the data of elemental analysis and NMR spectra. In NMR-spectra the result of alkylation has been confirmed by disappearance of the chemical shift of the mercapto group. All compounds both intermediate 4а-с and end products 6a-u and 7a-u contain signals of the alkyl protons of substituents in the triazole (methyl or methyl and methylene) ring; the 4-aminogroup protons are in the spectra of compounds 6 as singlet signals at 5.87-5.92 ppm. Modification of amino derivatives 6 into pyrrolyl substituted 7 is accompanied with the appearance of the characteristic signals of methyne protons of the pyrrole moiety instead of the signal of the amino group-triplet (positions 3,4) at 6.30-6.31 ppm and doublet (positions 2,5) at 7.21-7.24 ppm. Substances 7a, 7f, 7j and 7m were tested on the antitumour activity in vitro. As the result of this investigation it was noted that unfortunately all substances selected were not effective inhibitors of tumour cells in this dose.