Microwave-assisted Synthesis of Pyrazine-substituted Fluorobenzylamine Derivatives
Shakira Maharani Putri- Widiastuti Agustina Eko Setyowati- Puput Dyah Nur Safitri- Elfi Susanti VH- Sri Retno Dwi Ariani- Muhammad Hizbul Wathon

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

Abstract

Pyrazines and their derivatives are known to have broad biological activity, one of which is as antibacterials. Meanwhile, benzylamine is also known to have similar activity. In fluorobenzylamine, the highly electronegative and small fluoro substituent has the potential to increase metabolic stability, control the distribution of aromatic ring electrons, and maintain the balance of polarity and lipophilicity. The combination of the two has the potential to produce compounds with higher affinity for biological targets, making the development of new derivatives very important. Although not much research has been done, fluorobenzylamine-substituted pyrazine derivatives have the potential to have stronger biological activity, especially as antibacterials. This study aimed to produce fluorobenzylamine-substituted pyrazine derivatives and find a more efficient and effective synthesis method. Two 3-aminopyrazine-2-carboxamide derivatives were successfully synthesized, namely 3-amino-N-(3-fluorobenzyl)pyrazine-2-carboxamide (1), and 3-amino-N-(4-fluorobenzyl)pyrazine-2-carboxamide (2). The synthesis was carried out using conventional and microwave-assisted synthesis. The structure of the synthesized compounds was characterized using FTIR spectroscopy, NMR (H and C), and high-resolution mass spectrometry (HRMS), with results that were consistent with and supported the proposed molecular structure. The results showed that the ultrasound-assisted synthesis yielded higher yields and shorter reaction times and temperatures compared to the conventional method. The yields obtained through the conventional method were 60.79% for compound (1) and 72.01% for compound (2), while the microwave-assisted synthesis yielded higher results than the conventional method.

Keywords: ultrasound-assisted synthesis, pyrazine, fluorobenzilamina

Topic: Chemistry and Chemistry Education