Microwave synthesis of 3- and 4-substituted-5-((3-phenylpropyl)thio)-4H-1,2,4-triazoles

Abstract

The purpose of this work was to synthesize 3- and 4-substituted-5-((3-phenylpropyl)thio) 4H1,2,4-triazoles by the Milestone Flexi Wave microwave synthesis system and choose the best method of synthesis. Material and Method: The initial compounds 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol (1) and 5-(2-bromophenyl)-4-phenyl-4H-1,2,4-triazole-3-thiol (3) were synthesized at the Department of Natural Sciences for Foreign Students and Toxicological Chemistry of the Zaporizhzhya State Medical University (Ukraine). Milestone Flexi Wave microwave synthesis system was used to synthesize 3- and 4- substituted-5-((3-phenylpropyl)thio)-4H-1,2,4-triazoles. The elemental analysis of synthesized compounds was established by the universal analyzer Elementar Vario L cube (CHNS). The 1H spectra (at 400 MHz) were recorded in DMSO-d6 on a Varian MR-400 spectrometer and analyzed with ADVASP™ Analyzer program. The gas chromatograph Agilent 7890B with a 5977B mass spectrometry detector (US) was used to define the completeness of the reactions and the individuality of the resulting compounds. Result and Discussion: The reaction was carried out in i-propanol medium and an equivalent amount of sodium hydroxide. (3-Bromopropyl)benzene was added to starting substances 1 and 3. To study the completeness of the reaction, different reaction times were used. Conditions such as temperature, microwave radiation, pressure were unchanged. The temperature of the reaction mixture was kept at 1650C, pressure 12.2 bar, MW ≈ 540 W. The reaction time was set at 15 minutes, 30 minutes, and 45 minutes. The most effective reaction time for obtaining 3-(thiophen-2-ylmethyl)-4-amino-5-((3-phenylpropyl)thio)-4H-1,2,4-triazole (2) is 45 minutes. The most energy efficient reaction time for 3-(2-bromophenyl)-4-phenyl-5-((3-phenylpropyl)thio)- 4H-1,2,4-triazole (4) is 30 minutes heating. The signals of 1H NMR for compounds 2 and 4 are consented with the proposed structure. The elemental analysis (CHNS) was accomplished for synthesized compounds to confirm their basic chemical structures and revealed acceptable agreement with the calculated percentages.