Chemical Engineering Science 62 (2007) 5198 – 5200 www.elsevier.com/locate/ces Safety aspects of the process control of Grignard reactions H. Kryk a , ∗ , G. Hessel a , W. Schmitt a , N. Tefera b a Forschungszentrum Dresden-Rossendorf, P.O. Box 510119, D-01314 Dresden, Germany b Addis Ababa University, P.O. Box 385, Addis Ababa, Ethiopia Received 14 June 2006; received in revised form 12 December 2006; accepted 10 January 2007 Available online 25 January 2007 Abstract Grignard reactions comprise considerable hazard potentials due to the spontaneous heat release during the initiation of the exothermic reactions and the high reactivity of the Grignard compounds. To establish industrially applicable methods for an objective detection of the reaction start-up and for the accumulation of the organic halide during the process, calorimetric studies of a special Grignard reaction in a pressurised vessel were carried out using several on-line monitoring methods. In general, the process signal profiles, FTIR measurements and balance-based systems are applicable to provide the operator with additional information on the process state. Further experiments at adiabatic and isothermal conditions show significant influences of impurities (i.e., water) on the thermal process behaviour.  2007 Elsevier Ltd. All rights reserved. Keywords: Chemical processes; Grignard reaction; On-line monitoring; Process control; Safety; Chemical analysis 1. Objectives Metal-organic compounds like Grignard reagents are widely used to produce fine chemicals as well as pharmaceutical agents with complex molecule structures. Grignard reagents are com- monly prepared through reactions between organic halides and solid magnesium in an ethereal solution according to the fol- lowing simplified reaction equation: R-X organic halide + Mg(s) solid magnesium THF -→ R-Mg-X Grignard reagent H R =-200 ... - 350 kJ/mol Due to the spontaneous heat release during the initiation of these strongly exothermic reactions and the high reactivity of the Grignard compounds, Grignard reactions comprise consid- erable hazard potentials ( Yue et al., 1994). Primary sources of hazards can be attributed to a delayed reaction start due to traces of impurities (i.e., water concentration in the THF sol- vent) after the accumulation of a high amount of the organic halide or to undesired exothermic consecutive reactions of the Grignard reagent with such impurities. Therefore, it is of vital ∗ Corresponding author. Tel.: +49 351 260 2248; fax: +49 351 260 3651. E-mail address: h.kryk@fzd.de (H. Kryk). 0009-2509/$ - see front matter  2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.ces.2007.01.013 importance to establish industrially applicable methods for an objective detection of the reaction start-up and for the accumu- lation of the organic halide during the process. Furthermore, it is necessary to investigate the thermal behaviour of the un- desired consecutive reactions in order to evaluate the hazard potential of the industrial process. 2. On-line monitoring of Grignard reactions Usually, the preparation of Grignard reagents at industrial scale is carried out at a semi-batch regime by dosing the organic halide under boiling conditions using a reflux system to control the spontaneous strongly exothermic initiation reaction. How- ever, the process control under reflux conditions can lead to an increase of the hazard potential since the process signals of the reactor pressure and temperature cannot be used to detect the reaction start unless an additional sensor is used to measure the reflux flow rate. Furthermore, the open system and the reflux condenser represent potential malfunction sources since the risk of intrusion of impurities into the reaction mixture as well as the risk of emissions of hazardous substances are increased. Instead of operating under reflux conditions, the investi- gations were carried out in a pressurised vessel (RC1/HP60 calorimeter). In that way, an increase of the reactor temperature