SYNTHESIS OF HEART AND HYPERTENSION DRUGS ((±)-PROPRANOLOL AND (±)-IFOL) FROM BIO-BASED EPICHLOROHYDRIN

• Main Author: IRAWAN , JAMHUR
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/64749
• Institution: Institut Teknologi Bandung

Heart and blood vessel diseases such as hypertension, tremors, angina, and others are still the deadliest diseases in the world. Propranolol is a commercial drug of the beta blocker group which is currently widely used for the treatment of diseases related to the heart and blood vessels. The synthesis method of propranolol compounds generally uses the initial precursor in the form of epichlorohydrin. Epichlorohydrin can be synthesized using cheap and much available raw materials, such as glycerol through hydrochlorination and dehydrochlorination reactions. Currently, a lot of glycerol is produced as a waste from biodiesel fuel production, which is still very little utilization. In this study, propranolol and 1-isopropylamino- 3-phenoxypropan-2-ol (IFOL) compounds have been successfully synthesized and obtained by utilizing glycerol as an initial precursor to form epichlorohydrin. The synthesis stages of these compounds consisted of four stages, namely the synthesis of dichlorohydrin, epichlorohydrin, glycidyl-aryl-ether, then Propranolol and IFOL. The synthesized pure compounds were then characterized through Nuclear Magnetic Resonance (NMR) analysis. Dichlorohydrin compounds were synthesized by reacting glycerol with HCl gas using glacial acetic acid as a catalyst at 100oC for 24 hours. Based on the results of the GC-MS chromatogram, the compound was obtained in the form of a mixture of 1,3-dichlorohydrin and 2,3-dichlorohydrin with a concentration ratio of 4:1 respectively. The second step is the synthesis of epichlorohydrin by reacting a mixture of dichlorohydrin with NaOH at room temperature for 6 hours. Pure epichlorohydrin compound was obtained through simple distillation separation and obtained in the form of a clear liquid with 10.18% yield. In the third step, epichlorohydrin is reacted with ?-naphthol and phenol at room temperature using a NaOH catalyst for 10 hours to form glycidyl-?-naphthyl ether and glycidyl-phenyl ether compounds. The compound was purified by column chromatography and obtained in the form of a yellowish liquid with yield of 68.3 and 71.02% respectively. In the fourth step, glycidyl-?-naphthyl ether and glycidyl- phenyl ether were reacted with isopropylamine at 40oC for 4 hours respectively, to form propranolol and IFOL. The results of purification through recrystallization of the two compounds were obtained in the form of white solids with yields of 79.3 and 81.2%, respectively. The efficacy and purity of all synthesized compounds at each stage was confirmed and proven through analysis of 1H and 13C NMR spectrum data.