Resolution of asparagine in a coupled batch grinding process: experiments and modelling

A coupled batch grinding method is used to obtain resolution of a scalemic mixture of asparagine monohydrate conglomerate crystals, which are not racemizable in solution. For this method in two separate vessels a scalemic mixture of crystals is vigorously ground, while the two saturated solutions in contact with the crystals are continuously exchanged. Application of the method yields a 100% resolution with a yield of 50% (S) and 50% (R) crystals in the two vessels. To obtain a successful outcome, the grinding rates, temperatures and the amount of solids must be similar in both vessels. The experimental results are supported by a simple analytical model. It confirms that the process parameters are quite critical and that the incorporation of small clusters formed by grinding into the larger crystals of the same chirality is a prerequisite to obtain complete resolution.