A continuously operating spinning disk reactor (SDR) displayed distinct advantages over batch processing techniques when several commercially relevant processes for the manufacture of pharmaceuticals as test reactions were investigated. It proved to be a useful tool for revealing intrinsically fast kinetics as well as for optimizing processes with such kinetics. Very encouraging results were achieved for a phase-transfer-catalyzed (ptc) Darzen's reaction to prepare a drug intermediate and the recrystallization of an active pharmaceutical ingredient (API). In comparison to presently used batch processes, the ptc reaction resulted in a reaction with 99.9% reduced reaction time, 99% reduced inventory, and 93% reduced impurity level. The recrystallization yielded particles with a tight particle size distribution and a mean size of around 3 μm. Reactor modeling was in good agreement with the experimental results and highlighted the advantages of the process-intensified equipment with a production capacity of around 8 tonnes/year.

As part of an evaluation of equipment aimed at process intensification, use of a continuously operating spinning disc reactor (SDR) was investigated. Results obtained for two organic reactions and one crystallisation are discussed. The SDR was found to be a useful tool for revealling intrinsically fast kinetics as well as for optimising a process with such kinetics. Control of particle size distribution was demonstrated with the crystallisation investigated.

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Two plant syntheses of ropinirole {4-[2-(di-n-propylamino)ethyl]-1,3-dihydro-2H-indolin-2-one hydrochloride, SK&F-101468-A} using the ferric chloride mediated cyclisation of β-nitrostyrenes to form 3-chlorooxindoles as the key step are described. The first synthesis suffered the severe limitation of the final-step chemistry being nonselective in the reaction between di-n-propylamine and the bromide precursor to ropinirole as both substitution and elimination pathways were promoted and by-product formation at a level of 40% resulted. This problem was rectified in the latter synthesis by the more selective reaction between di-n-propylamine and the sulfonate ester precursor promoting ropinirole formation to a level of 88%. This second synthesis is now used as the commercial route, and problems (and their solutions) identified during the development of this route are now described. The identification of novel by-products which enabled the Sommelet oxidation step to be optimised is also reported. A unimolecular decomposition mechanism during hydrolysis of the hexaminium salt to form the key benzaldehyde intermediate is proposed and substantiated with experimental data.