THE APPLICAATION OF FREE-SOLVENT BECKMANN REARRANGEMENT IN THE SYNTHESIS OF PARACETAMOL

• Main Author: Putra, Anugrah
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/75382
• Institution: Institut Teknologi Bandung

The world pharmaceutical industry is one of the largest contributors to the world economy, the total revenue of the world pharmaceutical industry reaches 1.27 trillion U.S. dollars. In 2015-2019 the pharmaceutical industry in Indonesia experienced growth, which was marked by the increasing number of pharmaceutical industries in Indonesia. Although the pharmaceutical industry in Indonesia is growing, the production of medicines in Indonesia still depends on imported raw materials. In addition, the world's pharmaceutical industry also contributes a carbon footprint of 1.9 billion tons of CO2. Green chemistry is currently being applied on an industrial scale. Green Chemistry has several important principles including reducing waste generation, efficient use of materials and energy, using safer reagents, using renewable raw materials, using catalysts, reducing pollution, and reducing accidents due to hazardous chemicals. In this research, para-hydroxyacetophenone compounds are used which are widely found in Indonesia to synthesize paracetamol drug compounds. Paracetamol is known as one of the analgesic and antipyretic drugs that does not have anti-inflammatory effects, paracetamol is usually used to relieve fever and headaches. The application of green chemistry in the process of synthesizing paracetamol drug compounds is more environmentally friendly. One method of synthesizing paracetamol is the Hoechst-Celanese method which uses para-Hydroxyacetophenone compounds as raw materials. First of all, the compound para-Hydroxyacetophenone Oxime was obtained through the reaction between para-Hydroxyacetophenone mixed with hydroxylamine hydrochloride, sodium acetate, and water as the solvent. A reflux temperature of 90 °C with a reaction time of 4 hours in inert condition was used. The product of para-Hydroxyacetophenone Oxime which is not free of chloride ions (Cl- ) was obtained with a percent yield of 78.45%, while the product of para-Hydroxyacetophenone Oxime free of chloride ions was obtained with a percent yield of 15.64%. Furthermore, paracetamol synthesis was carried out using the oxime compound obtained, the oxime compound obtained was reacted with oxalic acid with a mole ratio of 1: 1 at the melting temperature of the mixture which was at 140 °C for 4 hours under inert conditions. The purified product in the form of paracetamol was obtained with a percent yield of 60.14%. In addition, the scale up reaction of paracetamol synthesis was also carried out, obtaining a product with a percent yield of 19.12%. Determination of the final structure of the compound obtained was carried out using Nuclear Magnetic Resonance (NMR), in addition to melting point tests, and comparison with standards.