Microwave-assisted Synthesis of 3-Amino-N-(4-Chlorophenyl)Pyrazine-2-Carboxamide and 3-Amino-N-(4-Bromophenyl) Pyrazine-2-Carboxamide
Imarotul Unsiyah,- Widiastuti Agustina Eko Setyowat-Endang Susilowati-Elfi Susanti Vh- Elvira Hermawati

Department of Chemistry Education, Faculty of Teacher Training and Education, Universitas Sebelas Maret, Jawa Tengah, Indonesia

Abstract

Pyrazine has broad biological activities, such as antibacterial, anticancer, and anti-inflammatory, and has been widely found as the basic framework of various drug. Meanwhile, aniline and its derivatives also exhibit diverse biological activities and show similar potential activities. The combination of these two structures has the potential to produce new compounds with stronger biological activities- however, the exploration of aniline-substituted pyrazine derivatives has not been widely conducted. This study aims to synthesize aniline-substituted pyrazine derivatives and obtain an effective synthesis method. Two aniline-substituted pyrazine derivatives were successfully synthesized In this study, namely 3-Amino-N-(4-Chlorophenyl) Pyrazine-2-Carboxamide (1) and 3-Amino-N-(4-Bromophenyl) Pyrazine-2-Carboxamide (2) from 3-aminopyrazine-2-carboxylic acid as the starting material. The synthesis was carried out using conventional and microwave-assisted synthesis. The structures of compounds 1 and 2 have been successfully determined based on FTIR, NMR (1H and 13C), and HRMS spectroscopy data. The FTIR spectrum shows the formation of amide groups through absorption at 1670-1674 cm-1 (C=O) and 3150-3320 cm-1 (N-H). The 1H NMR spectrum shows a characteristic signal of the amide proton at ~10.67ppm (bs), while the 13C NMR spectrum supports the presence of amide carbonyl at ~164.76 ppm. The HRMS spectrum obtained m/z [M+H]+ 251.0466, which corresponds to compound (1), and m/z [M+H]+ 294.9926, which corresponds to compound (2). These results indicate that the compounds have been successfully synthesized. The results show that the microwave-assisted synthesis provides higher yields and shorter reaction times and temperatures compared to the conventional method. The yields obtained through the conventional method for compounds (1) and (2) were 24.97% and 42.89%, respectively, while with microwave-assisted synthesis, they were 78.62% and 74.15%, respectively.

Keywords: microwave-assisted synthesis, pyrazine, aniline

Topic: Chemistry and Chemistry Education