3-Dialkylamino-1,2,4-triazoles via ZnII-Catalyzed Acyl Hydrazide-Dialkylcyanamide Coupling.

Sevilya N Yunusova,Vadim Yu Kukushkin,Peter M Tolstoy,Vitalii V Suslonov,Mikhail A Vovk,Dmitrii S Bolotin

doi:10.1021/acsomega.8b01047

Sevilya N Yunusova, Vadim Yu Kukushkin + Show 4 more

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https://doi.org/10.1021/acsomega.8b01047

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Journal: ACS omega	Publication Date: Jul 3, 2018
Citations: 8	License type: cc-by

Affiliation: St Petersburg University

Abstract

Zinc(II)-catalyzed (10 mol % ZnCl2) 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-NR2-1,2,4-triazoles, which utilizes commercially available and/or easily generated substrates. Seventeen new 3-NR2-1,2,4-triazoles were characterized by HRESI+-MS and IR, 1H, and 13C{1H} NMR spectroscopies and five species additionally by single-crystal X-ray diffraction (XRD). The ZnII-catalyzed reaction proceeds via initial generation of the [Zn{RC(=O)NHNH2}3](ZnCl4) complexes (exemplified by isolation of the complex with R = Ph, 76%; characterized by HRESI+-MS, IR, CP-MAS TOSS 13C{1H} 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.

Highlights

1,2,4-Triazole and its derivatives represent an important class of five-membered heterocycles, and many aspects of their versatile organic1,2 and coordination3,4 chemistry have been repeatedly reviewed over the years
We attempted the acyl hydrazide−dialkylcyanamide coupling under conditions similar to those employed for the preparation of 5-amino-1,2,4oxadiazoles from amidoximes and cyanamides
This work describes a novel highly efficient synthetic methodology for the synthesis of 3-dialkylamino-1,2,4-triazoles derived from ZnII-catalyzed acyl hydrazide and dialkylcyanamide coupling

Summary

INTRODUCTION

1,2,4-Triazole and its derivatives represent an important class of five-membered heterocycles, and many aspects of their versatile organic and coordination chemistry have been repeatedly reviewed over the years. The first method involves the reaction of acyl hydrazides with isothioureas (typically generated via Salkylation of thiourea in a separate synthesis) in the presence of a base (in H2O, RT, 1−3 d; 54−58%; a) to furnish Nunsubstituted 3-amino-1,2,4-triazoles. It is noteworthy that the method suggested in refs allows the synthesis of 3substituted-1,2,4-triazoles bearing only 1-indolinyl- or dialkylamino substituents as the NR2 group Another route includes the reaction of acyl hydrazides with cyanamides strongly activated by electron-withdrawing groups (in dioxane or DMF, reflux, 3−12 h; 30−76%; c).− This heterocyclization was successful only for monosubstituted cyanamides with electron-withdrawing substituents, for example, EWG = +C(NH2), C( O)Ar, or 2-(4,6-dimethylpyrimidyl). We established that the ZnIIcatalyzed reaction proceeds via initial generation of the [Zn{RC( O)NHNH2}3](ZnCl4) complexes and all our data are consistently disclosed in paragraphs that follow

RESULTS AND DISCUSSION

CONCLUSIONS

EXPERIMENTAL SECTION

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