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Facile Synthesis of 5-Aryl-N-(pyrazin-2-yl)thiophene-2-carboxamides via Suzuki Cross-Coupling Reactions, Their
Gulraiz Ahmad1, Nasir Rasool1, Adeel Mubarik1
1Department of Chemistry, Government College, University Faisalabad, Faisalabad 38000, Pakistan.
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 (EHOMO, ELUMO), 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.
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