Automated chemical synthesis. Part 4: Batch-type reactor automation and real-time software design

The ability to efficiently and comprehensively evaluate synthetic routes at their earliest stage of development is especially important in pharmaceutical process research and development and chemical engineering laboratories [1 and 2]. The evaluation and optimization of typically complex synthetic sequences (involving many reaction parameters) frequently entails bench-scale experimentation of a highly repetitive, manpower-intensive nature. While systems for pilot and production scale batch-type reactor automation are widely [3-6] available most bench-scale laboratory automation research has been applied to continuous-flow reactor schema [7-10]. Often, the first opportunity to design and test automation software is at the pilot scale and, therefore, requires large quantities of developmental chemical materials for experimentation. These pilot scale studies, undertaken at more advanced stages of process development, have little opportunity to affect the prerequisite process discovery and process research effort. The application of automation technology at earlier stages of the research and development programme would provide greater opportunities to guide synthetic route selection and optimization. Further, the automation models developed at this early stage could be applied to the subsequent pilot and production scale laboratories. The authors' research focuses on the design and construction of a computer-controlled bench-scale batch-type chemical reactor capable of self-directing experimentation, reaction optimization and extensive data acquisition [11-16]. An automated batch-type reactor apparatus must be capable of delivering precise amounts of chemical reagents and solvents to a vessel, controlling the reaction time and temperature, and performing on-line chemical analyses of the reaction solution. Costly reagents must be conserved; thus a basic design concern is the minimization of the vessel size. The precision and accuracy of reagent/solvent delivery systems, temperature control systems and the chemical analysis system are, of course, of fundamental concern. Furthermore, to permit unattended operation fail-safe features involving hardware and software self-checking and error trapping must assure instrument integrity.