Process control and real-time monitoring of Grignard reactions

 

Term: 01 / 2003 – 12 /2006

Funding: base funding

 

Grignard_Piktorgramm_engl

Goal

Metal-organic compounds like Grignard reagents are of vital importance as an initial stage of numerous organic syntheses in the fine-chemical and pharmaceutical industry. Grignard reactions possess considerable hazard potentials due to the spontaneous heat release during the initiation of these strongly exothermic reactions and the high reactivity of the Grignard compounds. For process safety reasons, it is of vital importance to establish industrially applicable methods for an objective real-time detection of the reaction start-up and for educt accumulations in the reaction mixture of the STR during the semi-batch process.

 

Methods

The following methods were tested to monitor Grignard processes in real-time:

  • use of primary process signals (temperature, pressure),
  • in-situ FTIR spectroscopy,
  • real-time heat/ mass balancing.

In order to use the above-named principles for an effective real-time monitoring, the process regime was modified. In contrast to the conventional process control of Grignard reactions at boiling temperature of the solvent using a reflux system, the process was investigated in a pressurised reactor at isoperibolic temperature control for the first time.

Reaktorbehälter1                      Reaktorbehälter

Conventional process regime (reflux system)                              Pressurised reaction vessel

 

Model process

The following reaction between bromobenzene derivative and magnesium in a THF solution was used as a model process to develop and test the real-time monitoring methods:

Grignard_Formel_engl

Since calorimetric measurements under reflux conditions produce higher errors than in closed systems, the reaction enthalpy was measured using the high pressure RC1e/HP60 calorimeter.

 

Results

In case of using the pressurised vessel configuration, all of the above-mentioned methods are suitable to monitor Grignard reactions in real-time. Monitoring methods using the primary process signals as well as the in-situ FTIR spectroscopy were tested during RC1/ HP60 experiments.

Grignard_Prozessgroessenverl Grignard_FTIR_Konz_verl
Courses of primary process signals during the Grignard reaction in a pressurised vessel Concentration profiles during the Grignard reaction in a pressurised vessel

 

The application of mass and energy balances to detect the reaction start-up and the educt accumulation was tested during experiments in a miniplant equipped with a 10 L STR.

online-Bilanzierung online-Bilanzierung1

Results of the heat/ mass balance approach compared to FTIR measurements

Results of the heat/ mass balance approach compared to FTIR measurements (optimised process regime)

In addition to the real-time monitoring of substance amounts and concentrations, the heat and mass balance approach opens new opportunities in safety oriented process control strategies as well as in process automation using real-time computing of safety relevant parameters. The approach provides an estimation of the hazard potential due to the reactivity of the organic halide accumulated in the reaction mixture.  Assuming an adiabatic behaviour as the worst case, the Maximum Temperature of the Synthesis Reaction (MTSR) and the related pressure pMTSR in the case of a runaway can be estimated as time-dependent functions and compared with pre-defined thresholds Tthres and pthres, respectively.

 

Grignard_MTSR     Grignard_pMTSR

Safety-relevant parameters MTSR and pMTSR during the Grignard reaction in a pressurised vessel

 

Summary

method

start-up detection

quantitative monitoring

pros

cons

primary process signals   (pR, TR)

+

-

easy to use

cost-efficient

dependent on process control

misinterpretations possible

on-line FTIR-spectroscopy (qualitative)

+

-

independent of process control

high investment cost

high operating costs

local measurement

on-line FTIR-spectroscopy (quantitative)

+

+

independent of process control

high investment cost

high operating costs

high calibration effort

local measurement

balance-based monitoring

+

+

cost-efficient

virtually independent of process control (pressurized vessel recommended)

advanced knowledge of process and plant parameters required

+ suitable              - unsuitable

 

Further information

Safety Aspects of the Process Control of Grignard Reactions  (Poster)

On-line monitoring of Grignard reactions (Presentation)

ISCRE-Poster

Grignard-Monitoring

 

Publications

  • Kryk, H.; Hessel, G.; Schmitt, W.
    Improvement of process safety and efficiency of Grignard reactions by real-time monitoring
    Organic Process Research & Development (2007), DOI: 10.1021/op700012g

  • Kryk, H.; Hessel, G.; Schmitt, W.; Tefera, N.
    Safety aspects of the process control of Grignard reactions
    Chemical Engineering Science 62(2007), 5198-5200

  • Kryk, H.; Hessel, G.; Schmitt, W.; Tefera, N.
    Gefahrenpotenziale bei Grignard-Reaktionen - Sichere Betriebsführung durch Online-Monitoring
    Technische Überwachung 46(2005)7/8, 41-47

 

Contact

Dr. H. Kryk