Clathrates with carboxylic acids

Carboxylic acids can also form clathrates. Xylene isomers can be separated by formation of clathrates with 1,1 -binaphthyl-2,2 -dicarboxylic acid.73 m-Xylene does not form a complex. The o-xylene complex decomposes at... 

Guest species that reside within clathrate hydrates do not participate in strong interactions with the water framework and are most often hydrophobic in nature. Molecules that are good hydrogen bond donors or acceptors (such as carboxylic acids, amines or alcohols) will disrupt the interactions between the water molecules and therefore prevent the hydrate network from forming. The most suitable guests are relatively small, non-polar species, such as halides, noble gases and small hydrocarbons. 

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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