Micro/milliflow processing with selective catalyst microwave heating in the Cu-catalyzed Ullmann etherification reaction: a µ(2)-process.

A µ(2)-process in the Ullmann-type C-O coupling of potassium phenolate and 4-chloropyridine was successfully performed in a combined microwave (MW) and microflow process. Selective MW absorption in a micro-fixed-bed reactor (µ-FBR) by using a supported Cu nanocatalyst resulted in an increased activity compared to an oil-bath heated process. Yields of up to 80 % were attained by using a multisegmented µ-FBR without significant catalyst deactivation. The µ-FBR was packed with beads coated with Cu/TiO(2) and CuZn/TiO(2) catalysts. Temperature measurements along axial positions of the reactor were performed by using a fiber-optic probe in the catalyst bed. The simultaneous application of MW power and temperature sensors resulted in an isothermal reactor at 20 W. Initially, only solvent was used to adjust the MW field density in the cavity and optimize the power utility. Subsequently, the reaction mixture was added to ensure the maximum MW power transfer by adjusting the waveguide stub tuners to steady-state operations as a result of the changed reaction mixture composition and, therefore, the dielectric properties. Finally, the beneficial influence of the Cu/TiO(2)- and CuZn/TiO(2)-coated glass beads (200 µm) on the MW absorption as a result of the additional absorbing effect of the metallic Cu nanoparticles was optimized in a fine-tuning step. For the catalyst synthesis, various sol-gel, deposition, and impregnation methods provided Cu catalyst loadings of around 1 wt %. The addition of Zn to the Cu nanocatalyst revealed an increased catalyst activity owing to the presence of stable Cu(0). Multilaminar mixing was necessary because of the large difference in fluid viscosities. To the best of our knowledge, this work is the first extended experimental survey of the decisive parameters to combine microprocess and single-mode MW technology following the concepts of "novel process windows" for organic syntheses.

New Cu-based catalysts supported on TiO2 films for Ullmann S(N)Ar-type C-O coupling reactions.

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)).

Effect of the load size on the efficiency of microwave heating under stop flow and continuous flow conditions.

A novel heating efficiency analysis of the microwave heated stop-flow (i.e. stagnant liquid) and continuous-flow reactors has been presented. The thermal losses to the surrounding air by natural convection have been taken into account for heating efficiency calculation of the microwave heating process. The effect of the load diameter in the range of 4-29 mm on the heating efficiency of ethylene glycol was studied in a single mode microwave cavity under continuous flow and stop-flow conditions. The variation of the microwave absorbing properties of the load with temperature was estimated. Under stop-flow conditions, the heating efficiency depends on the load diameter. The highest heating efficiency has been observed at the load diameter close to the half wavelength of the electromagnetic field in the corresponding medium. Under continuous-flow conditions, the heating efficiency increased linearly. However, microwave leakage above the propagation diameter restricted further experimentation at higher load diameters. Contrary to the stop-flow conditions, the load temperature did not raise monotonously from the inlet to outlet under continuous-flow conditions. This was due to the combined effect of lagging convective heat fluxes in comparison to volumetric heating. This severely disturbs the uniformity of the electromagnetic field in the axial direction and creates areas of high and low field intensity along the load Length decreasing the heating efficiency as compared to stop-flow conditions.

Microwave-induced electrostatic etching: generation of highly reactive magnesium for application in Grignard reagent formation.

A detailed study regarding the influence of microwave irradiation on the formation of a series of Grignard reagents in terms of rates and selectivities has revealed that these heterogeneous reactions may display a beneficial microwave effect. The interaction between microwaves and magnesium turnings generates violent electrostatic discharges. These discharges on magnesium lead to melting of the magnesium surface, thus generating highly active magnesium particles. As compared to conventional operation the microwave-induced discharges on the magnesium surface lead to considerably shorter initiation times for the insertion of magnesium in selected substrates (i.e. halothiophenes, halopyridines, octyl halides, and halobenzenes). Thermographic imaging and surface characterization by scanning electron microscopy showed that neither selective heating nor a "specific" microwave effect was causing the reduction in initiation times. This novel and straightforward initiation method eliminates the use of toxic and environmentally adverse initiators. Thus, this initiation method limits the formation of by-products. We clearly demonstrated that microwave irradiation enables fast Grignard reagent formation. Therefore, microwave technology is promising for process intensification of Grignard based coupling reactions.

Switching from S- to R-selectivity in the Candida antarctica lipase B-catalyzed ring-opening of omega-methylated lactones: tuning polymerizations by ring size.

Novozym 435-catalyzed ring-opening of a range of omega-methylated lactones demonstrates fascinating differences in rate of reaction and enantioselectivity. A switch from S- to R-selectivity was observed upon going from small (ring sizes or=8). This was attributed to the transition from a cisoid to a transoid conformational preference of the ester bond on going from small to large lactones. The S-selectivity of the ring-opening of the small, cisoid lactones was low to moderate, while the R-selectivity of the ring-opening of the large transoid lactones was surprisingly high. The S-selectivity of the ring-opening of the small, cisoid lactones combined with the established R-selectivity of the transesterification of (aliphatic) secondary alcohols prevented polymerization from taking place. Ring-opening of the large, transoid lactones was R-selective with high enantioselectivity. As a result, these lactones could be polymerized, without exception, by straightforward kinetic resolution polymerization, yielding the enantiopure R-polyester with excellent enantiomeric excess (>99%).