FUNCTIONALIZATION OF ORTHO POSITION ON 4-ACETYLPHENOL AS PRECURSORS FOR SALBUTAMOL SYNTHESIS

• Main Author: Lis Masa Miranti, Anisa
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/75214
• Institution: Institut Teknologi Bandung

Asthma can cause chronic inflammation of the respiratory tract, which can cause shortness of breath and other symptoms. Asthma is a health problem in Indonesia which is quite serious due to the large number of asthma sufferers in Indonesia. Salbutamol is a drug that is widely used to relieve asthma. Therefore, the availability of the drug salbutamol in Indonesia is very important to meet the drug needs of the community. Currently Indonesia imports more than 90% of active pharmaceutical ingredients. This situation causes Indonesia to become a dependent country on imported medicinal raw materials. Therefore, in this work 4-acetylphenol, derived by acetylation of phenol, was used as a precursor for the synthesis of salbutamol because this compound could be produced in Indonesia. In addition, the proposed synthesis of salbutamol improves the current strategy, which complies with several green chemistry principles, namely preventing environmental pollution and waste o from toxic and hazardous chemicals. In this work, salbutamol was synthesized by functionalizing the ortho position in 4-acetylphenol. The reaction of 4-acetylphenol and paraformaldehyde in a mixture of glacial acetic acid and concentrated hydrochloric acid at room temperature produces 6-acetyl-1,3-benzodioxane as a white solid with a low yield of 4.7%. In contrast, the formylation of 4-acetylphenol under the Reimer-Tiemann condition, in which 4-acetylphenol was reacted with chloroform in ethanol under basic conditions of NaOH and triethylamine (Et3N) for 8 hours, produces 5-acetyl-2-hydroxybenzaldehyde as a yellow solid in a higher yield 6.9%. The same condition in a shorter time of 4 hours results the product in a yield of 3.9%. The replacement of a base with KOH furnishes the product with a better yield of 14.2%. The two obtained compounds, namely 6-acetyl-1,3-benzodioxane and 5-acetyl-2-hydroxybenzaldehyde, are the important precursors in the synthesis of the asthma drug salbutamol. Determination of the structure of pure products was characterized by using NMR spectroscopy.