Facile Synthesis of 5-Aryl- N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions, Their Electronic and Nonlinear Optical Properties through DFT Calculations

Gulraiz Ahmad; Nasir Rasool; Adeel Mubarik; Ameer Fawad Zahoor; Muhammad Ali Hashmi; Muhammad Zubair; Muhammad Bilal; Mohamed Hussien; Muhammad Saeed Akhtar; Sajjad Haider

doi:10.3390/molecules26237309

Facile Synthesis of 5-Aryl- N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions, Their Electronic and Nonlinear Optical Properties through DFT Calculations

Molecules. 2021 Dec 2;26(23):7309. doi: 10.3390/molecules26237309.

Affiliations

¹ Department of Chemistry, Government College, University Faisalabad, Faisalabad 38000, Pakistan.
² Department of Chemistry, University of Education Lahore, Attock Campus, Attock 43600, Pakistan.
³ Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia.
⁴ School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Korea.
⁵ Chemical Engineering Department, College of Engineering, King Saud University, P.O. Box 800, Riyadh 11421, Saudi Arabia.

Abstract

Synthesis of 5-aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides (4a-4n) by a Suzuki cross-coupling reaction of 5-bromo-N-(pyrazin-2-yl)thiophene-2-carboxamide (3) with various aryl/heteroaryl boronic acids/pinacol esters was observed in this article. The intermediate compound 3 was prepared by condensation of pyrazin-2-amine (1) with 5-bromothiophene-2-carboxylic acid (2) mediated by TiCl₄. The target pyrazine analogs (4a-4n) were confirmed by NMR and mass spectrometry. In DFT calculation of target molecules, several reactivity parameters like FMOs (E_HOMO, E_LUMO), HOMO-LUMO energy gap, electron affinity (A), ionization energy (I), electrophilicity index (ω), chemical softness (σ) and chemical hardness (η) were considered and discussed. Effect of various substituents was observed on values of the HOMO-LUMO energy gap and hyperpolarizability. The p-electronic delocalization extended over pyrazine, benzene and thiophene was examined in studying the NLO behavior. The chemical shifts of ¹H NMR of all the synthesized compounds 4a-4n were calculated and compared with the experimental values.

Keywords: 1H NMR comparison; FMO analysis; NLO properties; Suzuki coupling; pyrazine; thiophenecarboxamide.