ChemicalBook CAS DataBase List Piroxicam

Piroxicam synthesis

8synthesis methods

Product Name:Piroxicam
CAS Number:36322-90-4
Molecular formula:C15H13N3O4S
Molecular Weight:331.35

Piroxicam, 1,1-dioxid-4-hydroxy-2-methyl-N-2-pyradyl-2H-1,2-benzothiazine- 3-carboxamide (3.2.78), is synthesized from saccharin (3.2.70). Two methods for saccharin synthesis are described. It usually comes from toluene, which is sulfonated by chlorosulfonic acid, forming isomeric 4- and 2-toluenesulfonyl chlorides. The isomeric products are separated by freezing (chilling). The liquid part, 2-toluenesulfonyl chloride (3.2.68) is separated from the crystallized 4-toluenesulfochloride and reacted with ammonia, giving 2-toluenesulfonylamide (3.2.69). Oxidation of the product with sodium permanganate or chromium (VI) oxide in sulfuric acid gives saccharin—o-sulfobenzoic acid imide (3.2.70).

An alternative way for making saccharin is from methyl ester o-aminobenzoic (anthranylic acid). This undergoes diazotization using nitrous acid, and the resulting diazonium salt (3.2.71) is reacted with sulfur dioxide in the presence of copper dichloride, forming the methyl ester o-sulfobenzoic acid (3.2.72). Reaction of the resulting product with chlorine gives o-chlorosulfonylbenzoic acid methyl ester (3.2.73), which upon reaction with ammonium gives o-sulfonylamidobenzoic acid methyl ester (3.2.74). In the presence of hydrogen chloride, the resulting product undergoes cyclization into saccharin (3.2.70).

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36322-90-4
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Yield:-

Steps:

Multi-step reaction with 3 steps
1: CHCl₃
2: 25 percent / sodium isopropoxide / propan-2-ol / 0.67 h / 140 °C
3: 210 mg / 0.94N NaOH / H₂O; methanol / Ambient temperature

References:

Perillo;Schapira;Lamdan [Journal of Heterocyclic Chemistry,1983,vol. 20,# 1,p. 155 - 160]

15448-99-4 Synthesis