Lumbertus A. Hulshof

Lipases in the preparation of β-blockers

Abstract β-Adrenergic blocking agents are pharmaceutical products used for the treatment of hypertension and angina pectoris. These β-blockers can be prepared in optically active form by conventional crystallization procedures, by asymmetric chiral synthesis and by using stereoselective enzymes.

Highly sustainable catalytic dehydrogenation of alcohols with evolution of hydrogen gas

The catalytic dehydrogenation of alcohols into aldehydes and ketones in the absence of H-acceptors was studied with several transition metal catalysts in order to develop a large-scale procedure. Applying Ru(OCOCF3)2(CO)(PPh3)2, the so called Robinson catalyst, several secondary alcohols could be dehydrogenated with high selectivity into the corresponding ketones in relatively short reaction times. Highly effective atom utilization could be realized avoiding solvents and giving hydrogen gas as the sole by-product. However, in contrast to Robinsons work the catalytic dehydrogenation of primary alcohols appeared to be problematic due to decarbonylation with concomitant catalyst deactivation and aldol condensation under the strong acid or basic conditions applied.

The mechanism of the oxidation of benzyl alcohol by iron(III)nitrate: Conventional versus microwave heating

The mechanism of the oxidation of benzyl alcohol with iron(III)nitrate nonahydrate under conventional and under microwave heating conditions has been investigated and the reaction conditions have been optimized. A series of redox reactions leads to the formation of benzaldehyde and other products. Direct comparison between conventional and microwave heating revealed identical conversions profiles. Mastering the microwave induced heat, absence of a real microwave effect and byproduct formation are the major factors to advise a traditional batch-wise way of process development to a larger scale.

RACEMATSPALTUNGEN MIT SUBSTANZFAMILIEN

Die Racematspaltung revolutionieren konnte das hier vorgestellte kombinatorische Verfahren, bei dem Gemische („Familien”) strukturell und stereochemisch verwandter Reagentien mit den zu trennenden racemischen Sauren oder Basen umgesetzt werden. Die in ublicherweise einem Schritt gebildeten diastereomeren Salze fallen fast immer rasch aus, Ausbeuten und Enantiomerenuberschusse sind gut bis hervorragend. Auch Reagensgemische mit racemischen oder achiralen Komponenten wurden entwickelt.

Effect of the Load Size on the Efficiency of Microwave Heating Under Stop Flow and Continuous Flow Conditions

Abstract 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.

Dutch resolution of racemic 4-hydroxy- and 4-fluorophenylglycine with mixtures of phenylglycine and (+)-10-camphorsulfonic acid

Abstract 4-Hydroxyphenylglycine and 4-fluorophenylglycine can be resolved with (+)-10-camphorsulfonic acid only if dl - or d -(−)-phenylglycine is added. When using dl -phenylglycine this is co-resolved in this process. In this resolution process mixed crystals are formed of the (+)-10-camphorsulfonic acid salts of the d -(−)-enantiomers of phenylglycine and the para substituted phenylglycines. In the crystal lattice of the mixed salts approximately 25–30% of the d -(−)-phenylglycine molecules can be randomly replaced by d -(−)-para substituted phenylglycines, resulting in the desired resolution. The overall non-stoichiometric composition of the mixed crystals reflects to some extent the composition in solution. This behaviour is typical for solid solutions. The solid solution behaviour in this so called ‘Dutch resolution’ is proven by differential scanning calorimetry (DSC), X-ray crystal structure determination and powder diffraction.

New Cu-Based Catalysts Supported on TiO2 Films for Ullmann SNAr-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)).

Chiral polymers by iterative tandem catalysis

Racemic omega-substituted caprolactones can be completely converted into chiral polyesters of remarkable MW and high ee by combining lipase-catalyzed ring-opening polymerization with Ru-catalyzed racemization.

Asymmetric borane reduction using mixtures of homochiral amino alcohol ligands

The asymmetric borane reduction of acetophenone is investigated using mixtures of homochiral β-amino alcohol ligands. With stoichiometric amounts of a mixture of two- or three-amino alcohols, the e.e. remains at the level of the best amino alcohol for a wide composition range. A small but statistically significant enhancement in e.e. is observed when 10 mol% of an amino alcohol mixture of (1S,2R)-1-amino-2-indanol and (S)-phenylglycinol is used as chiral ligand.