3-Dialkylamino-1,2,4-triazoles via Zn^II-Catalyzed Acyl Hydrazide–Dialkylcyanamide Coupling

Abstract

Zinc(II)-catalyzed (10 mol % ZnCl 2 ) coupling of acyl hydrazides and dialkylcyanamides in ethanol leads to 3-dialkylamino-1,2,4-triazoles (76–99%; 17 examples). This reaction represents a novel, straightforward, and high-yielding approach to practically important 3-NR 2 -1,2,4-triazoles, which utilizes commercially available and/or easily generated substrates. Seventeen new 3-NR 2 -1,2,4-triazoles were characterized by HRESI + -MS and IR, 1 H, and 13 C{ 1 H} NMR spectroscopies and five species additionally by single-crystal X-ray diffraction (XRD). The Zn II -catalyzed reaction proceeds via initial generation of the [Zn{RC(= O )NH N H 2 } 3 ](ZnCl 4 ) complexes (exemplified by isolation of the complex with R = Ph, 76%; characterized by HRESI + -MS, IR, CP-MAS TOSS 13 C{ 1 H} NMR, and XRD). Electronic effects of substituents at the acyl hydrazide moiety do not significantly affect the reaction rate and the yield of the target triazoles, whereas the steric hindrances reduce the reaction rate without affecting the yield of the heterocycles.

Solvent- and functional-group-assisted tautomerism of 3-alkyl substituted 5-(2-pyridyl)-1,2,4-triazoles in DMSO–water

“…However, Kubota and Uda concluded from 1 H NMR data in CDCl 3 that 3- p -substituted phenyl-5-methylthio-1,2,4-triazoles exist predominantly in form A (position of the NH relative to the SMe substituent) for electron donating substituents ( p -NH 2 , p -OMe) and in form B for substituents with electron withdrawing character ( p -Cl, p -NO 2 ) or when the aromatic substituent was 3-pyridyl. 28 In DMSO- d 6 as solvent, the 1 H NMR spectra of a relatively large series of 3(5)-amino-1,2,4-triazoles containing aryl, 29 heteroaryl 29 a and amidoalkyl 30 substituents consisted of mixtures of isomers A and B , the latter being favoured. It has recently been reported that the three tautomers of a 1,2,4-triazol C-disubstituted with carbamoyl and mercaptoethyl moieties are present in the ratio of 54 : 32 : 14 in the 1 H NMR spectrum measured in DMSO- d 6 .…”

Anti-inflammation and antimalarial profile of 5-pyridin-2-yl-1H-[1,2,4]triazole-3-carboxylic acid ethyl ester as a low molecular intermediate for hybrid drug synthesis

“…The combination of amide and acyl hydrazide is generally referred to as the Pellizzari Reaction (developed in 1894) and can be used to obtain 3,5-diphenyl-1,2,4-triazole at 140 °C [ 11 ]. A recent synthetic example is a procedure based on zinc(II)-catalysed acyl hydrazide-dialkylcyanamide coupling, which allows the utilization of cyanamides bearing donor alkylsubstituents and gives 3-dialkylamino-1,2,4-triazoles such as 3-dimethylamino-5-phenyl-1,2,4-triazole under mild conditions and in high yields [ 12 ]. Another example is the intramolecular ring closure of acyl-amidrazonzes, using tosyl-amidrazone treated with acetyl chloride to obtain 5-methyl-3-(2’,3’,4’,6’-tetra-O-benzoyl-b-D-glucopyranosyl)-1-tosyl-1,2,4-triazole [ 13 ].…”

Base Mediated Diazirination via Iodine(III) Reagents

“…An extensive literature survey revealed that hydrazides have been widely employed in the synthesis of heterocyclic compounds. , With this in mind, we envisaged that a carbohydrazide bearing a semicarbazide (−C­(O)­NHNH 2 ) functional group could be one of the best choices as a reaction partner in coupling with diazo compounds. Currently, the key complication in the synthesis of diazirines is the lack of simple and efficient protocol.…”