Microwave-assisted Synthesis of Pyrazine-substituted Chlorinated-benzylamine Derivatives Celicarina Anwar- Widiastuti Agustina Eko Setyowati- Dina Oktaviya Adi Putri- Elfi Susanti VH- Muhammad Hizbul Wathon
Department of Chemistry Education, Faculty of Teacher Training and Education, Universitas Sebelas Maret, Jawa Tengah, Indonesia
Abstract
Pyrazine and their derivatives are known to have broad biological activity, while chlorinated benzylamine has advantages due to its reactive amino group and stable chlorinated benzyl ring, which increases lipophilicity. Modification of pyrazine compounds with chlorinated benzylamine substituents has the potential to improve their chemical properties and biological activity, but this has not been widely explored. This study aims to synthesize chlorobenzylamine-substituted pyrazine derivatives and obtain a more optimal synthesis method. Three 3-aminopyrazine-2-carboxylic acid derivatives have been successfully synthesized, namely 3-amino-N-(3-chlorobenzyl)-pyrazine-2-carboxamide (1), 3-amino-N-(4-chlorobenzyl)-pyrazine-2-carboxamide (2), and 3-amino-N-(2,4-dichlorobenzyl)-pyrazine-2-carboxamide (3). The synthesis was carried out using two different methods, conventional and microwave-assisted synthesis. The structures of the synthesized compounds were characterized using FTIR spectroscopy, NMR (1H and 13C), and HRMS. The FTIR results show characteristic C=O amide absorption at 1653 cm-1, N-H bands at 3392-3146 cm-1, and C-N amine at 1149 cm-1. The 1H-NMR data showed aromatic proton signals at 7.30-7.83 ppm, -CH2- signals at 4.42 ppm, and amide protons (-NH) at 7.53 ppm. The 13C-NMR spectrum confirmed the presence of carbonyl at 166 ppm, aromatic carbon at 125-155 ppm, and -CH2- at 41 ppm. HRMS data showed peaks with m/z [M+H]+ corresponding to compounds 1, 2, and 3. The microwave-assisted synthesis yielded higher yields and shorter reaction times and temperatures compared to the conventional method. The yields from the conventional method for compounds 1, 2, and 3 were 59.66%, 65.86%, and 58.76%, respectively, while those using the microwave-assisted synthesis were 78.67%, 92.29%, and 93.34%, respectively. This study confirms that the microwave-assisted synthesis is an efficient alternative for the synthesis of chlorobenzylamine-substituted pyrazine.
