SOLVENT-FREE SYNTHESIS OF PARACETAMOL
Paracetamol (N-acetyl-para-aminophenol) is the most widely used analgesic and antipyretic in the world. In Indonesia, paracetamol is known as one of the largest imported pharmaceuticals. There are two major industrial processes of paracetamol production, namely production via acetylation of...
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| Format: | Theses |
| Language: | Indonesia |
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| Online Access: | https://digilib.itb.ac.id/gdl/view/57449 |
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| Institution: | Institut Teknologi Bandung |
| Language: | Indonesia |
| Summary: | Paracetamol (N-acetyl-para-aminophenol) is the most widely used analgesic and antipyretic in the world. In Indonesia, paracetamol is known as one of the largest imported pharmaceuticals. There are two major industrial processes of paracetamol production, namely production via acetylation of p-hydroxy aniline and via Beckmann's rearrangement of p-hydroxy acetophenone oxime (called as Hoechst-Celanase Process or HC process). From a green chemistry perspective of pharmaceutical manufacturing, the HC process has a lot of advantages, in particular atom economy and E-factor. The raw material used in the HC process is phenol, a widely used material in the chemical industry. In a conventional HC process, Beckmann rearrangement takes place mediated by thionyl chloride (SOCl2) with liquid SO2 as a solvent which will produce corrosive HCl as a by- product. In this work, we successfully demonstrate a free-solvent Beckmann’s rearrangement by using oxalic acid as a reagent. Firstly, the reaction between para-hydroxy acetophenone and NH2OH.HCl with sodium acetate as a catalyst in
4 hours at 90 °C furnishes the intermediate oxime in 94% yield. Finally, the key
step of Beckmann rearrangement of the oxime takes place at the melting temperature of the mixture of p-hydroxy acetophenone oxime and oxalic acid with a mole ratio of 1: 1 in 30 minutes to produce paracetamol in 61% yield. All products were purified by crystallization or chromatography and characterized by spectroscopic methods or comparison with a standard compound.
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