Synthesis, crystal structure and Hirshfeld surface analysis of N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide

Abstract

The title compound, C19H17ClN4O2, was obtained via a two-step synthesis involving the enol-mediated click Dimroth reaction of 4-azidoanisole with methyl 3-cyclopropyl-3-oxopropanoate leading to the 5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid and subsequent acid amidation with 4-chloroaniline by 1,1′-carbonyldiimidazole (CDI). It crystallizes in space group P21/n, with one molecule in the asymmetric unit. In the extended structure, two molecules arranged in a near coplanar fashion relative to the triazole ring planes are interconnected by N—H...N and C—H...N hydrogen bonds into a homodimer. The formation of dimers is a consequence of the above interaction and the edge-to-face stacking of aromatic rings, which are turned by 58.0 (3)° relative to each other. The dimers are linked by C—H...O interactions into ribbons. DFT calculations demonstrate that the frontier molecular orbitals are well separated in energy and the HOMO is largely localized on the 4-chlorophenyl amide motif while the LUMO is associated with aryltriazole grouping. A Hirshfeld surface analysis was performed to further analyse the intermolecular interactions.

Synthesis, crystal structure and Hirshfeld surface analysis of 5-cyclopropyl-N-(2-hydroxyethyl)-1-(4-methylphenyl)-1H-1,2,3-triazole-4-carboxamide

“…A similar location of the cyclopropyl ring relative to the 1,2,3-triazole ring was also observed in 5-cyclopropyl-1-(3methoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (Pokhodylo et al, 2017), but in the structure of the related compound N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide (Pokhodylo & Slyvka et al, 2020), the cyclopropyl ring is close to coplanar with the aryl substituent. An intramolecular N4-H4Á Á ÁN3 close contact (HÁ Á ÁN = 2.37 Å ; N-HÁ Á ÁN = 106 ) is observed.…”

“…In our previous studies, new active compounds with a 1,2,3triazolyl-4-carboxamide motif were reported (Shyyka et al, 2019;Pokhodylo, Shyyka, Finiuk & Stoika, 2020;Pokhodylo, Slyvka & Pavlyuk, 2020). Additionally, 1,2,3-triazolyl-4carboxamide derivatives were found to be inhibitors of the Wnt/-catenin signalling pathway (Obianom et al, 2019).…”

“…most closest related compounds containing a similar 1-aryl-1H-1,2,3-triazole-4-carboxamide skeleton to the title compound but with different substituents on the amide are: N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide(Pokhodylo & Slyvka et al, 2020), (S)-1-(4-chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (I)[Cambridge Structural Database (Version 2021.1;Groom et al, 2016) refcode ZIPSEY;Shen et al, 2013], 1-(4-chlorophenyl)-5-methyl-N-[(3-phenyl-1,2-oxazol-5-yl)methyl]-1H-1,2,3-triazole-4-carboxamide (II) (LELHOB;Niu et al, 2013), (5-methyl-1-[8-(trifluoromethyl)quinolin-4-yl]-1H-1,2,3-triazol-4-yl)morpholino)methanone (III) (LOHWIP;Anuradha et al, 2008) and 1-(3-amino-5-(3-hydroxy-3-methylbut-1-yn-1yl)phenyl)-N-butyl-1H-1,2,3-triazole-4-carboxamide (IV) (BEBJEZ;Li et al, 2012).Compounds (I) and (II) crystallize in the monoclinic crystal system with space groups P2 1 and P2 1 /c, respectively, while compounds (III) and (IV) crystallize in the triclinic space group P1. Structure (I) contains two crystallographically independent molecules, the hydroxyl groups of which participate in intermolecular O-HÁ Á ÁO hydrogen bonds.…”