(180b) Chemical Synthesis in Micro Reactors

The miniaturisation of chemical reactors offer many fundamental and practical advantages of relevance to the pharmaceutical industry, who are constantly searching for controllable, information rich, high throughput, environmentally friendly methods of producing products with a high degree of chemical selectivity. Micro reactors used for chemical synthesis usually consist of a network of micron-sized channels etched into a solid substrate. For solution-based chemistry, the channel networks are connected to a series of reservoirs containing chemical reagents to form the complete device with overall dimensions of a few cm. Reagents can be brought together in a specific sequence, mixed and allowed to react for a specified time in a controlled region of the channel network using either electrokinetic or hydrodynamic pumping.

A concerted effort has now begun to establish the benefits that micro reactors can bring to the field of synthetic chemistry. For example, the ability to manipulate reagent concentrations in both space and time within the channel network of a micro reactor provides an additional level of reaction control which is not attainable in bulk stirred reactors where concentrations are generally uniform. Consistent with this notion, many single-step reactions have been demonstrated to show altered reactivity, product yield and selectivity when performed in micro reactors as compared with conventional bench top glassware. A selection of such reactions will be reviewed within this presentation.

Micro reactor chemistry is currently showing great promise as a novel method on which to build new chemical technology and processes. Reactions performed within a micro reactor invariably generate relatively pure products in high yield in short periods of time and in sufficient quantities to perform full instrumental characterisation. One of the immediate and obvious applications is therefore in combinatorial chemistry and drug discovery, where the generation of compounds with either different reagents or under variable conditions is an essential factor. In order to prepare complex products, of the type required by pharmaceutical companies, it is necessary to conduct multi-step reactions. In order to achieve such results it is important to be able to manufacture and use reagents in situ, examples of such reactions will be discussed.

The use of solid supported reagents adds even greater diversity to the range of reactions that may be achieved within such systems. It will be demonstrated that the dimensions of reactors may be increased in size while maintaining the classic advantages associated with miniaturisation. In such systems significant quantities of analytically pure compound may be prepared without additional purification.