?-BROMINATION OF ACETOPHENONE DERIVATIVES WITH PYRIDINIUM TRIBROMIDE IN A FLOW MICROREACTOR

• Main Author: Kevin
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/81389
• Institution: Institut Teknologi Bandung

Asthma is a long-term inflammatory disease that is characterized by wheezing, coughing, shortness of breath and chest tightness. Environmental factors, such as increased air pollution may lead to an increase in the number of asthma patients in the future. Because of that, the demand of bronchodilators, such as salbutamol, may increase in the future. Salbutamol works by binding to ?2-andrenergic receptors as an agonist and cause the widening of the respiratory tract. One of the important reaction stage of salbutamol synthesis is ?-bromination reaction. Generally, ?-bromination is carried out with bromine (Br2), but this process is unsafe and needs special treatment because bromine is toxic, corrosive, and difficult to handle properly. Therefore, researchers are seeking out alternatives to bromine, such as N-bromosuccinimide (NBS) and pyridinium tribromide (PyHBr3). Several advantages of PyHBr3 includes easier handling and can be accurately weighed because it is a stable and solid reagent. The reaction is done in small-scale reactor through a microtube which the reactants are mixed and flowed through. In this research, ?-bromination of acetophenone are carried out using PyHBr3 in room temperature. The resulting product is 2-bromo-1-phenylethan-1-one and 2,2-dibromo-1 phenylethan-1-one, which was isolated in 23% and 3% yield, respectively. The product mixture obtained is then purified by column chromatography and characterized by 1H-NMR and 13C-NMR spectroscopy. Optimization of ?-bromination of acetophenone is done in flow reactor by varying the temperature, total flow rate, and equivalence of acetophenone:PyHBr3. The reaction was found to be optimal at 50 °C, total flow rate of 1,5 mL/minute, and equivalency of 1:1,25. This optimized condition is then used to brominate p hydroxyacetophenone, 2,4-dihydroxyacetophenone, and 2,4,6,-trihydroxyacetophenone. Bromination of p-hydroxyacetophenone yields the ?-bromination product as a major product, while 2,4-dihydroxyacetophenone and 2,4,6-trihydroxyacetophenone undergo electrophilic substitution.