A continuously operated microwave heated millireactor setup has been developed for performing reactions of highly microwave absorbing media in a controlled and energy efficient manner. The setup consists of a tubular reactor integrated with a heat exchanger. A microwave transparent liquid was used as coolant to extract the excess heat from the reaction mixture, thus controlling the temperature of the reaction mixture by avoiding overshoots and subsequent boiling. A reactor‐heat exchanger shell and tube unit with a diameter of the inner tube of 3·10−3 m and a shell of 7·10−3 m inner diameter has been manufactured in quartz. The unit size was defined based on simulation with a heat‐transfer model for the microwave cavity part. Microwave heating was incorporated as a volumetric heating source term using the temperature‐dependent dielectric properties of the liquid. Model predictions were validated with measurements for a range of 0.167·10−6 to 1.67·10−6 m3/s flow rates of coolant. The outlet temperature of both the reaction mixture and the coolant, were predicted accurately (tolerance of 3 K), and the process window was determined. The model for the reactor part provided the required length of the reactor for a hetero‐geneously catalyzed esterification reaction. The predicted conversions, based on the obtained temperature profile in the reactor packed with the catalyst bed, known residence times and kinetics of the esterification reaction, were found to be in good agreement with the experimental results. Efficient utilization of microwave energy with heat recovery up to 20% of the total absorbed microwave power and heating efficiencies up to 96% were achieved. It has been demonstrated that the microwave heating combined with millireactor flow processing provides controlled and energy efficient operation thus making it a viable option for a fine chemical production scale of 1 kg/day (24 h period). © 2011 American Institute of Chemical Engineers AIChE J, 58: 3144–3155, 2012

We report the first liquid−liquid Ullmann etherification process mediated not only by oxidatively stable Cu but also by CuZn and CuSn nanoparticle catalysts in conjunction with microwave heating that also avoids the use of solid and expensive bases. Conditions have led to improved turnovers and excellent yields in heteroaromatic Ullmann-type coupling reactions. Further enhancement is achieved upon the addition of 18-crown-6 as a kinetic promoter.

An extended cost study consisting of 14 process scenarios was carried out to envisage the cost impact of microprocessing and microwaves separately or in combination for two liquid-phase model reactions in fine-chemicals synthesis: (1) Ullmann C-O cross-coupling reaction and (2) the aspirin synthesis. The former, a Cu-catalyzed substitution reaction, was based on an experimental investigation, whereas the latter, a noncatalyzed aromatic esterification reaction, was based on literature data. The cost of 4-phenoxypyridine production, as a pharmaceutical intermediate in the synthesis of vancomycin or vancocin, was compared with that of the synthesis of aspirin, a key example of large-scale fine-chemical production plants. The operating costs in the Ullmann synthesis were found to be related to materialbased process (reactant excess, pretreatment, and catalyst synthesis), whereas those in the aspirin synthesis appeared to be related to downstream-based process (workup, waste treatment). The impact of an integrated microwave heating and microprocessing system on profitability was demonstrated with respect to operational cost and chemical productivity. Different modes of microwave heating and catalyst supply were studied and compared with conventional oilbath-heated systems in batch and continuous processes. The overall costs including profitability breakthrough for a competitive market price of product were obtained from various combinations of heating and processing. In case of the Ullmann synthesis, the CAPEX (capital expenditure) was negligible compared to the OPEX (operational expenditure), whereas in the aspirin synthesis, the CAPEX was found around 40%, both at a production scales of 1-10 kg/day using proposed upscale methods. The source of the catalyst strongly determined the profitability of a continuously operated Ullmann process due to its effect on the chemical performance. Higher energy efficiencies could be attained using single-mode microwave irradiation; however, the energy contribution to the overall cost was found to be negligible. Different scenarios provided a cost-feasible and profitable process; nevertheless, an integrated microwave heating and microflow processing led to a cost-efficient system using a micropacked-bed reactor in comparison to wall-coated microreactor, showing a profit margin of 20%.

A design methodology is proposed to maintain gas and liquid flow nonuniformities below an acceptable limit in a parallel micro/millichannels reactor by determining the maximum allowed temperature deviation in each part of the reactor. The effect of temperature deviation on flow distribution was quantified using a hydraulic resistive network model. The effect of flow rate on temperature deviation was demonstrated using a one-dimensional energy balance model. Experiments were conducted using the barrier-based micro/millichannels reactor (BMMR). Flow distribution in the BMMR is based on placing hydraulic resistances (barrier channels) in the gas and liquid manifolds to regulate the flows. Temperature deviation in the barrier channels affects flow nonuniformity by 10 times more than in the reaction channels. Above a certain critical liquid residence time, flow rate has no significant effect on the temperature deviation which depends on the liquid used, reactor material of construction, and its geometrical dimensions.

New routes for the preparation of highly active TiO(2)-supported Cu and CuZn catalysts have been developed for C-O coupling reactions. Slurries of a titania precursor were dip-coated onto glass beads to obtain either structured mesoporous or non-porous titania thin films. The Cu and CuZn nanoparticles, synthesized using a reduction by solvent method, were deposited onto calcined films to obtain a Cu loading of 2 wt%. The catalysts were characterized by inductively coupled plasma (ICP) spectroscopy, temperature-programmed oxidation/reduction (TPO/TPR) techniques, (63)Cu nuclear magnetic resonance (NMR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy (S/TEM-EDX) and X-ray photo-electron spectroscopy (XPS). The activity and stability of the catalysts obtained have been studied in the C-O Ullmann coupling of 4-chloropyridine and potassium phenolate. The titania-supported nanoparticles retained catalyst activity for up to 12 h. However, catalyst deactivation was observed for longer operation times due to oxidation of the Cu nanoparticles. The oxidation rate could be significantly reduced over the CuZn/TiO(2) catalytic films due to the presence of Zn. The 4-phenoxypyridine yield was 64% on the Cu/nonporous TiO(2) at 120 °C. The highest product yield of 84% was obtained on the Cu/mesoporous TiO(2) at 140 °C, corresponding to an initial reaction rate of 104 mmol g(cat) (-1) s(-1). The activation energy on the Cu/mesoporous TiO(2) catalyst was found to be (144±5) kJ mol(-1), which is close to the value obtained for the reaction over unsupported CuZn nanoparticles (123±3 kJ mol(-1)) and almost twice the value observed over the catalysts deposited onto the non-porous TiO(2) support (75±2 kJ mol(-1)).