O-Thymotic acid

If thymol be treated with sodium and a current of carbonic acid be passed through it, o-thymotic acid is formed, which when liberated by means of hydrochloric acid and purified by distillation, melts at 123°. Thymotic acid has the constitution—... 

Until recently, the only reported product of the condensation of o-thymotic acid 1 by phosphoric anhydride or phosphorous oxychloride was a mixture of di-o-thymotide (DOT) and tri-o-thymotide in moderate yield. In order to improve the yield of TOT a careful reinvestigation of the reaction with POCI3 or dicyclohexylcarbodiimide as condensation agents was carried out by Arad-Yellin et al. Several other esters were indeed isolated and characterized (2, 3, 4). It was suggested that these products are competitively generated by the facile decarboxylation of the intermediate compound 5 on the reaction path to intramolecular esterification. Good evidence was obtained that the hydroxy group assists decarboxylation of 5. 

Farias and Hosangadi had previously studied the selective action of polyphosphate ester on the condensation reaction of o-thymotic acid. The process is characterized by the selective formation of the eight-membered di-o-thymotide at the expense of TOT. Mechanistic aspects for this specific cyclisation reaction are unknown at the present time. 

The Kolbe-Schmitt reaction has been used as a key step in natural product synthesis. The early syntheses of isotubaic acid (Rotenic acid) used a Kolbe-Schmitt reaction in the final step. " Shriner and co-workers converted isotubanol (22) to its sodium salt under anhydrous conditions, then heated the phenoxide with solid carbon dioxide at 180 °C in a sealed reaction vessel to give an 86% yield of the natural product. Sheehan and co-workers also used the Kolbe-Schmitt reaction to prepare an early intermediate in the synthesis of gossypol where thymol is efficiently converted to o-thymotic acid in 65% yield. ... 

Hydroxy-6-methyl-3-isopropylbenzoic acid o-Thymotic acid C11H44O3 548-51-6 194.227 nd (w, bz, lig) 127 sub vs bz, eth, EtOH... 

B.S. Green and co-workers developed an improved preparation of the clathrate host compound tri-o-thymotide (TOT) and other trisalicylide derivatives. The synthesis began with the preparation of orfho-thymotic acid from thymol using the Kolbe-Schmitt reaction. The authors found that the yield of the product was dramatically increased when the reactants, solvents, and reagents were dried before use. Thus, thymol was dissolved in dry xylene, sodium metal was added and the temperature was kept at 130 °C for 20h in a dry carbon dioxide atmosphere. The desired carboxylated product was isolated in good yield. Finally, cyclodehydration with POCI3 afforded TOT in almost quantitative yield. 

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