On the Kolbe-Schmitt synthesis of pharmacologically useful salicylates: Carboxylation of 2,4-di-t-butylphenol and identification and reduction of the formation of 2,2′-dihydroxy-3,3′,5,5′-tetra-t-butylbiphenyl in the synthesis of 3,5-di-t-butylsalicylic acid

✍ Scribed by Mankulathu V. Chidambaram; John R. J. Sorenson

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 290 KB
• Volume: 80
• Category: Article
• ISSN: 0022-3549
• DOI: 10.1002/jps.2600800822

✦ Synopsis

The initial yield of 3,5-di-t-butylsalicylic acid obtained via Kolbe-Schmitt carboxylation of the potassium salt of 2,4-di-t-butylphenol was less than 1% and was accompanied by a 65% yield of 2,2'-dihydroxy-3,3',5,5'- tetra-t-butylbiphenyl, a dimer of the 2,4-di-t-butylphenol formed by ortho coupling of phenoxide radicals. Formation of this dimer was decreased to 8%, and the yield of 3,5-di-t-butylsalicylic acid was increased to 68% by optimizing reaction time and temperature and decreasing the amount of oxygen present during carboxylation. This modification of the Kolbe-Schmitt reaction conditions may be generally helpful in the synthesis of all pharmacologically useful salicylates.