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Process screening by multi-reactor synthesis aids development

1st April 2013


The competition to develop new and better chemicals, particularly for pharmaceutical applications, has been assisted by a range of tools that did not exist even three years ago. Dr Jasbir Singh reports.

In terms of the synthetic chemist's perspective, there are primarily three steps in going from idea to market: discovery of key molecule, screening of routes to produce the molecule and then development/scale up of a process to manufacture the product.

The second of these steps, screening of routes (also sometimes called route scouting) is crucial ­ time is of the essence so that some samples of the material can be produced for trials. The cost of production is irrelevant, it is important only to get the right quality in the shortest possible time.

If the chemist can quickly try out lots of permutations that should theoretically work, in order to find the one that works best, he can greatly improve the competitive edge.

A number of tools for process screening are coming on the market ­ mostly launched over the last 12 months ­ and one of these, Chem-SCAN, will be described in this article to illustrate the main features.

There are two versions of the Chem-SCAN, high-pressure (metal) unit for catalyst screening and a low-pressure (glass) design for general-purpose synthesis reactions.

The former involves eight reactors, with an operating volume of around 3 to 8 ml, each of which is individually stirred by small anchor-shaped mechanical stirrer and may sit within a temperature controlled block. The reactors can be run at pressures of up to 100 bar.

The primary applications to date have involved heterogeneous (gas/liquid/solid) catalyst development where good mixing is paramount. The system in its simplest form, allows the reactors to be run at any user defined pressure and temperature and monitors the relative rates of gas (for example hydrogen) uptake so that activity levels of catalysts is immediately evident.

The objective is to allow easy comparison of different catalysts and find near-optimal conditions of temperatures and pressure.

More advanced versions will provide more accurate information on the rates of gas uptake and can also charge liquids to the reactor, at pressure.

The low pressure, glass version of the Chem-SCAN is also based around eight-reactor blocks but in this case multiple blocks can be used to test greater combinations of variables. The reactors are again placed in heated blocks and are stirred in the same way as the high-pressure version ­ ideal for multi-phase synthesis.

The key difference here is that the blocks site on a robot abed', where a needle attached to high precision dispensing pumps is used to move reagents around.

Thus, each reactor can be charged with solvents and reagents in different quantities, the reactors can be sampled followed by dilution/quenching at user defined intervals.

If necessary, simultaneous injection into an HPLC unit can also be carried out ­ the Chem-SCAN has the distinction of supporting a range of chromatography systems.

As with many systems of this type, facilities exist for gas purging of reactors as well as operation under reflux. One of the key aspects that distinguish robotic-based screening systems is the ease with which the user is able to program his individual requirements.

The Chem-SCAN supports visual capability (drag-and-drop) for specification of robot actions and the availability of useful Macros to carry out complex operations with a single command (for example, sampling). It also has a library that permits commands for complete plans to be stored for subsequent repetition or merging with other plans.

Data is displayed in different forms (bar charts, line graphs, etc) to permit easy assimilation of results, in real time.

ENQUIRY No 57

Dr Jasbir Singh is managing director of Hazard Evaluation Laboratory Limited, Barnet, Hertfordshire, UK. www.helgroup.co.uk





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