SYNTHESIS OF THE CARDIAC DRUG BISOPROLOL USING 4-((2-ISOPROPOXYETHOXY)METHYL)PHENOL PRECURSOR

• Main Author: Violeta, Vanessa
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/75434
• Institution: Institut Teknologi Bandung

The Republic of Indonesia's Ministry of Health focuses on Indonesia's capacity to independently develop medications that are extensively used by its populace. Bisoprolol, a medication for cardiovascular illness, is among them. To interact with the hormone adrenaline, the ?-blocker medication bisoprolol preferentially blocks ?1- adrenergic receptors. As a result, bisoprolol can reduce blood pressure and heart rate. As a result, the objective of this study is to synthesize bisoprolol using a precursor of 4-(2-isopropoxyethoxy)methyl)phenol and identify the ideal conditions for the synthesis reactions. The synthesis of 2-((4-((2- isopropoxyethoxy)methyl)phenoxy)methyl)oxirane, bisoprolol, and bisoprolol hemifumarate were the three chemical steps that made up this study. By changing the amounts of epichlorohydrin (2, 3, 4, and 5 equivalents), bases (K2CO3, Cs2CO3, and KOH), solvents (acetonitrile, ethanol, and 1,2-dichloroethane), temperatures (60, 80, and 100 oC), and reaction times (1, 2, and 3 hours), the conditions for the synthesis of 2-((4-((2-isopropoxyethoxy)methyl)phenoxy)methyl)oxirane were improved. Acetonitrile as the solvent, 2 equivalents of epichlorohydrin, KOH base, 100 oC, and an hour-long reaction period were the ideal conditions. By adjusting the reaction duration (1, 2, 3, and 4 hours) and temperature (45, 55, 60, and 65 oC), the conditions for the synthesis of bisoprolol were improved. The best results were obtained with a temperature of 65 oC and 4 hours reaction time. Thin layer chromatography (TLC) was used to qualitatively analyze each product, and 1H NMR (500 MHz) and 13C NMR (125 MHz) spectroscopy was used to clarify its structure. In this study, 2-((4-((2- isopropoxyethoxy)methyl)phenoxy)methyl)oxirane, crude bisoprolol, and bisoprolol hemifumarate were effectively produced with conversion rates of 91% and yield of 86, 52, and 3%, respectively. In the end, this study's strategy for producing 2-((4-((2- isopropoxyethoxy)methyl)phenoxy)methyl)oxirane and bisoprolol yields superior outcomes than earlier studies.