Synthesis of Celecoxib in the Undergraduate Organic Chemistry or Medicinal Chemistry Laboratories; Conventional vs. Microwave Heating

TCE

The Chemical Educator

ISSN: 1430-4171 (electronic version)

Table of Contents

Abstract Volume 18 (2013) pp 155-158
DOI 10.1007/s00897132496

Synthesis of Celecoxib in the Undergraduate Organic Chemistry or Medicinal Chemistry Laboratories; Conventional vs. Microwave Heating

Marko Anderluh

Department of Medicinal Chemistry, Faculty of Pharmacy, Aškerčeva 7, SI-1000 Ljubljana, Slovenia, marko.anderluh@ffa.uni-lj.s
Received April 26, 2013. Accepted May 18, 2013.

Published: 5 July 2013

Abstract. A method for a two-step synthesis of celecoxib in the undergraduate organic chemistry or medicinal chemistry laboratories is reported. The experiment requires two 3.5 hour lab periods and the standard equipment for organic/medicinal chemistry course, plus a monomode microwave reactor. In the first session, students condense 4-methylacetophenone and ethyl trifluoroacetate to yield 4,4,4-trifluoro-1-(p-tolyl)butan-1,3-dione. The latter is then condensed in a second session with 4-hydrazinobenzene-1-sulfonamide hydrochloride to yield corresponding 1,5-arylpyrazole (celecoxib) using either conventional heating or microwave-assisted synthesis. Both procedures give a crystalline product with a reasonably high yield that is easy to isolate and purify, and both procedures are robust and practical. The 1H-NMR spectra of both intermediate and final product are easily interpreted by the students. The comparison of both procedures used for the same reaction offers an excellent basis to demonstrate the advantages of the microwave-assisted over conventional heating.

Key Words: Laboratories and Demonstrations; organic chemistry; medicinal chemistry; aldehydes/ketones; addition/elimination (condensation) reactions; heterocycles; microwave heating; hands-on learning; third-year undergraduate

(*) Corresponding author. (E-mail: marko.anderluh@ffa.uni-lj.s )

Article in PDF format (651 KB) HTML format

Supporting Materials:

A list of required chemicals and equipment; Instructions for students; Instructor notes; Short introduction to Synthesis of Alkoxides and Introduction Into Microwave-Assisted Organic Synthesis; 1H NMR spectra of intermediate and final product; Student report sheet; Sample questions for students (672 KB).