In this work, we examine the chromatographic purification of the chiral amide N-(2-methyl-benzylidene)-phenylglycine amide (NMPA). Specifically, we find that its adsorption behavior on an AY polysaccharidic chiral stationary phase (amylose tris(5-chloro-2-methylphenylcarbamate)), with acetonitrile as mobile phase, follows an uncommon type-1 mixed Langmuir isotherm. Moreover, we measure the racemization rate of NMPA when polymer-supported 1,8-diazabicycloundec-7-ene (DBU) is used as a catalyst in a fixed-bed reactor. We also determine the system's solid−liquid equilibria at different temperatures. This characterization is necessary for the design of an integrated process where simulated moving bed (SMB) chromatography is combined with racemization for the recycle of the undesired enantiomer. On the basis of the physicochemical properties above, three-column intermittent SMB (3C-ISMB) experiments were run at different concentrations and compositions to prove that an enantiopure product can be obtained when the separation is operated at high feed concentrations (nonlinear chromatographic conditions) in the case not only of a racemic feed but also of nonracemic feeds, which are relevant for the integrated process when racemization is slow, and thus incomplete.

We address the purification of the target enantiomer of a chiral compound from its racemic mixture, through simulated moving bed (SMB) chromatography either as a standalone or combined with the recycle and racemization of the undesired enantiomer. We carry out a comparative assessment of the two processes with focus on the role of the racemization kinetics, on the effect of the selectivity of the chiral stationary phase, and of the upstream symmetric synthesis of the racemate. The analysis is general thanks to the methods adopted for the optimal design of the integrated process (with racemization) and for the sizing of the SMB unit, as well as for the use of the four generalized Langmuir adsorption isotherms. In this way, we determine quantitative criteria that show that the standalone SMB process outperforms the integrated process when the performance of the racemization catalyst or the chiral stationary phase is poor and the racemic feed is inexpensive.

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