Menthol resolution with DBTA

Combined thermoanalytical (TA,TGA and DSC) investigations of DBTA complexes of chiral alcohols may serve valuable data on the composition and stabilities of these solid supramolecular compounds. DSC monitoring of menthol resolution with DBTA in melt has already discussed in point 3.4. Thermal stability of further ten complexes of DBTA with alcohols 26, 29-31, 35-37 and 39-41 was also determined. [47] The melting points of the DBTA complexes (Table 11) increase in the 2-alkanol, 2-alkoxycyclohexanol, 2-halogenocyclohexanol order. 

Optical resolution of menthol (28) with DBTA in hexane suspension is quite efficient (S = 0.374, Table 5 [38]) but complex formation is slow. In order to increase the reaction rate, the highest possible concentrations of the reactants were reached by solving DBTA monohydrate in the melt of racemic menthol. [41]... 

In this case the resolving agent should be added to the racemic compound and the mixture should be warmed until it melted then is should be cooled while one of the diastereoisomers crystallizes from the melt. The ciystalline material can be separated by filtration from the residue of the melt (as in case of enantiomeric mixtures). An example for this method is the resolution of racemic menthol (MEN) with 0,0 -dibenzoyl-(J ,J )-tartaric acid ((R,R)-DBTA). The crystalline molecular complex (diastereoisomer) contains the (lJ ,2S,5J )-menthol (the L-menthol (L-MEN)), while the remained melt is enriched in the other enantiomer ... 

The melting point of racemic 28 is 33 °C therefore clean liquid could be obtained by gentle heating of the mixture. As far as the stirred reaction mixture cooled down to 25 °C, the unreacted optically active menthol could be withdrawn from the solid by simple extraction [41] (Scheme 15). The yield and enantiomeric enrichment depends on the molar ratio of the racemate and DBTA (Table 8). The most efficient resolution of 28 was accomplished with half an equivalent DBTA (S = 0,456) and this result is significantly better then the selectivity of the original resolution in hexan (S = 0,37). 

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