Simple Synthesis Tools for the Next Generation

Tue, 09/05/2006 - 5:54am

A scalable, modular approach can yield productivity gains while being effective, adaptable, cost-effective and easy to use. Here are eight important points to consider

'Everything should be made as simple as possible, but not simpler.' —Albert Einstein Richard Gray
<Simple, adj: having few parts; not complex or complicated or involved. Simplistic, adj: overly simplified, not including all the factors that actually should be considered.
R&D chemists are familiar with the difficulties inherent in using automation while attempting to increase productivity in the laboratory. Synthetic chemistry is complex and often not well characterized. Processes demand extreme temperatures, and equipment needs to have chemically resistant construction. Flexibility is restricted by the need to achieve realistic system costs. On the other hand, the basic tools for manual synthesis could hardly be simpler — a glass round-bottom flask, a stirrer bar and a heater plate. Why is it so hard to turn such a simple starting point into reliable, usable automated tools at reasonable cost? This article will focus on the simpler end of the range of automated systems and avoid the more complex robotic systems. The objective is to identify the characteristics of an ideal synthesis tool, which is simple to use but not so simple as to be simplistic. Some vendors have tried to create simple tools by staying close to the roots of manual technology. Such systems, often based on blocks and carousels, offer some improvement in productivity by organizing the chemist but arguably only in much the same way that a Filofax organizes a manager. The systems essentially make more efficient use of the chemist's time in the lab, yet still require the chemist's attendance to control the process and carry out all steps of the reaction. Additionally, any one system can only cope with a very small range of the chemist's repertoire. Because so many tools are required to cover the full spectrum of needs and since these tools are inevitably very different in design, use and operation, the goal of simplicity is lost. Many current systems fail on two counts. First, they do not achieve enough benefit within their area of usability. Second, they force the chemist to collect a battery of incompatible tools in an attempt to create a comprehensive toolset. The word "simplistic" is a better description for such an approach. So, how could this situation be improved? Consider one well-known solution from a different field. The SLR camera is a perfect example of a rugged, simple, yet scalable tool. From the starting point of a camera body (or base unit), the user can add lenses, motor drives, flash units, databacks, filters, etc., to create any desired setup — from the basic point-and-shoot to a high-performance professional tool. Each sub-module is relatively affordable, interchangeable and easy to use. Could such an approach be applied to synthesis tools? The following eight points form an outline specification for an ideal synthesis platform. It's a modular approach that can yield a flexible and scalable solution suited to specific needs. 1. The system should allow synthesis over a usable range of discovery and development needs — for example, from 50 ml to 1 liter. 2. The base system should have easy mechanical support and should be able to accommodate a range of round-bottom flasks or jacketed vessels. Changing vessels should be very quick and easy, requiring no tools. 3. An ability to heat and cool should be provided, using programmed temperature ramps if required rather than just a simple on/off function. 4. A simple means of active cooling at the end of a heating step should be available, ideally without having to resort to recirculating chillers. Where recirculators are needed for more extreme temperatures, it should be possible to connect and disconnect oil pipes to the vessel without tools and with no oil spills. 5. The system should be able to support automated reagent addition while ensuring that the reaction temperature is maintained. 6. Temperature control should be by internal or external reaction monitoring, depending on need. 7. Magnetic stirring should be available for ease, with simple-to-set-up overhead stirring available for viscous and larger-scale reactions. 8. The equipment should not be limited to running only single reactions or high throughput reactions. It should be able to do both easily. It should also be operable with simple non-software control, but if the chemist prefers, software should be available for data logging and sophisticated control. Richard Gray is commercial director and co-founder of Syrris Inc, 29 Albion Place, Charlestown, MA 02129, a leading supplier of productivity tools for R&D chemists including flow reactor systems, controlled lab reactors and reaction monitoring systems. His technical background is in engineering automated synthesis systems. Questions about this article can be addressed to him at, 516-312-3028 or 617-848-2997. Additional information can be found at

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