Racemization during derivatization

Another important point to consider is the prevention of racemization during derivatization. It is also a problem that the reagent needs to be present in excess during the reaction if this excess cannot be removed prior to injection an interfering peak may occur in the chromatogram. 

Srinivas, N. R. Clinical pharmacokinetic data of racemic drugs obtained by the indirect method following precolumn diastereomer formation Is the influence of racemization during chiral derivatization significant Biomed. Chromatogr, 2004, 18, 343-349. 

There can be no accidental resolution, deresolution, or racemization during a derivatization (but beware of enantiomer enrichment during sample purification, vide supra). 

Commenls The preparation of alcoholic HCl can also be carried out in silu by the addition of acetyl chloride to the dry chiral alcohol [8]. Although the conditions used for these reactions are harsh, the authors reported no evidence of racemization during the derivatization of naproxen [54] even after an extended reaction time of 23 h. Lee el al. [64], however, observed a small peak, corresponding to approximately 2%, when enantiomeri-cally pure ibuprofen was derivatized under the conditions described in procedure C the results could have been attributed to either racemization or the presence of impurities in the substrates or reagents. 

Derivatization requires that the species of interest must contain a functional group that can be chemically modified. There should be no enantioselectivity of the rate of the derivatization. There are several disadvantages to an indirect chromatographic chiral separation. The derivatization procedure may be complex and time-consuming and there is always a possibility of racemization during the derivatization procedure. In the case of preparative chromatography of the diastereomeric species, they have to be... 

Table 7 shows a series of alcohols analyzed with the Alexakis reagent. In the 31P-NMR spectra, alcohol derivatives appear as two singlets (P—H decoupled) corresponding to each diastereomer. Shift differences are about 10 times larger in the primary, nonthionated product. No racemization could be observed during the derivatization step as demonstrated with ethyl lactate and hydrobenzoin. 

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