In our laboratory, we have investigated several synthetic reactions implemented on the mjod milli-reactor system, first with the goal to benchmark batch (laboratory flask) and micro-reactor protocols with the procedures achieved with the mjod milli-reactor system. Thereafter optimizing the mjod milli-reactor system in order to obtain large throughputs, and to investigate reactor aspects from an chemical engineers point of view.

Scheme 1. The haloform reaction used for the synthesis of veratric acid 1 using acetoveratron 2 as substrate.

Scheme 2. The Suzuki cross-coupling reaction for the synthesis of 2-nitrobiphenyl.

The protocol was easily implement on the mjod milli-reactor system, to obtain improved results.Phenyl boronic acid 4 was reacted under batch conditions with 1-iodo-2-nitrobenzene 5 to provide a yield of 30% of 2-nitrobiphenyl 6 with a reaction time of 30 min. and acetone/water as the reaction medium.

     Several more synthetic reactions and processes have been mplemented on the mjod milli-reactor system for example: Nef Reaction, Oxidation, Nucleophilic Aromatic Substitution, Sodium Borohydride Reduction, O-Allylation, Paal-Knorr Condensation, Hoffmann Rearrangement, and Ring closing metatheis.
    
     Some of these reactions have also been attempted developed into high throughput procedures. For example, the sodium borohydride reduction performed on cyclohexanone, has been successfully developed to provide practically quantitative yield with a production capacity of ~350 g h.-1 This example and other organic process examples will be discussed in more detail during the lecture.
    
     Characterization of the reactor system is still in progress, but preliminary results shows that the extreme mixing that takes place in the reactor system accelerate substantially synthetic reactions compared to reactions performed in batch. Reactions that require phase transfer catalyst may be conducted with a minimum of the PTC present.

The Flow Chemistry System.
     The mjod milli-reactor system that was used for the syntheses examples mentioned above was an advance prototype of the multi-jet oscillating disc linear milli-reactor system. A corresponding to a set-up as shown in Figure 3. This mjod milli-reactor set-up has an effective volume of ~38 mL and is equipped with a multi-jet oscillating disc baffle insertion assembly with disc sizes that cover the whole cross section of the tubular reactor. In total there are 59 interbaffle cavities composed by 60 discs.
    
     A variable-frequency, variable-amplitude oscillator was used for the piston movement of the assembly of the multi-jet oscillating discs. An electric motor connected to a cam mechanism was used as the motive power for the piston motion (the assembly of the multi-jet oscillating discs).
Additionally, the cam assembly provided control of the amplitude by linear translation of the cam assembly to predefined positions. Frequencies in the 0.5-10 Hz and amplitudes in the range of 0.5-20 mm can be achieved by adjusting the motor speed and cam assembly.

Feeding of substrate and reagents.
     Standard piston feeding pumps or peristaltic pumps were used to feed the reactants into the reactor body. Heating and temperature control were performed by using standard circulation baths connected to the heating/cooling circuits of the milli-reactor.

References / Notes