Frank King

Tunable gold catalysts for selective hydrocarbon oxidation under mild conditions

Oxidation is an important method for the synthesis of chemical intermediates in the manufacture of high-tonnage commodities, high-value fine chemicals, agrochemicals and pharmaceuticals: but oxidations are often inefficient. The introduction of catalytic systems using oxygen from air is preferred for ‘green’ processing. Gold catalysis is now showing potential in selective redox processes, particularly for alcohol oxidation and the direct synthesis of hydrogen peroxide. However, a major challenge that persists is the synthesis of an epoxide by the direct electrophilic addition of oxygen to an alkene. Although ethene is epoxidized efficiently using molecular oxygen with silver catalysts in a large-scale industrial process, this is unique because higher alkenes can only be effectively epoxidized using hydrogen peroxide, hydroperoxides or stoichiometric oxygen donors. Here we show that nanocrystalline gold catalysts can provide tunable active catalysts for the oxidation of alkenes using air, with exceptionally high selectivity to partial oxidation products (∼98%) and significant conversions. Our finding significantly extends the discovery by Haruta that nanocrystalline gold can epoxidize alkenes when hydrogen is used to activate the molecular oxygen; in our case, no sacrificial reductant is needed. We anticipate that our finding will initiate attempts to understand more fully the mechanism of oxygen activation at gold surfaces, which might lead to commercial exploitation of the high redox activity of gold nanocrystals.

QUASI: A general purpose implementation of the QM/MM approach and its application to problems in catalysis

Abstract We describe the work of the European project QUASI (Quantum Simulation in Industry, project EP25047) which has sought to develop a flexible QM/MM scheme and to apply it to a range of industrial problems. A number of QM/MM approaches were implemented within the computational chemistry scripting system, ChemShell, which provides the framework for deploying a variety of independent program packages. This software was applied in several large-scale QM/MM studies which addressed the catalytic decomposition of N 2 O by Cu-containing zeolites, the methanol synthesis reaction catalysed by Cu clusters supported on ZnO surfaces, and the modelling of enzyme structure and reactivity.

Accelerated asymmetric transfer hydrogenation of aromatic ketones in water

Asymmetric transfer hydrogenation of various simple aromatic ketones by the Ru-TsDPEN catalyst was shown to be feasible in aqueous HCOONa without calling for any catalyst modification, furnishing ees of up to 95% and significantly faster rates than in the HCOOH-NEt(3) azeotrope.

Promotion of Fe3O4/Cr2O3 high temperature water gas shift catalyst

Abstract The promotion of Fe 3 O 4 /Cr 2 O 3 high temperature water gas shift catalysts is described and discussed. Catalysts containing 2 wt% B, Cu, Ba, Pb, Hg and Ag are prepared by co-precipitation. B is found to poison the activity slightly whereas the other additives did increase the activity, with the relative order being Hg>Ag,Ba>Cu>Pb>unpromoted>B. The promoters decrease the activation energy of the catalyst, but the data give a linear relationship for the Constable–Cremer plot and it is concluded that CO adsorption is an important factor controlling activity.

Phenyl benzenesulfonamides are novel and selective 5-HT6 antagonists: identification of N-(2,5-dibromo-3-fluorophenyl)-4-methoxy-3-piperazin-1-ylbenzenesulfonamide (SB-357134)

Substituted N-phenyl-4-methoxy-3-piperazin-1-ylbenzenesulfonamides and conformationally restricted analogues have been identified as high affinity and selective 5-HT6 antagonists. Compounds from this series had a range of pharmacokinetic profiles in rat and in general there was a correlation between clearance and CNS penetration. Based on its overall biological profile 2 (SB-357134) was selected for further pre-clinical evaluation.

Effects of the novel high-affinity 5-HT(1B/1D)-receptor ligand frovatriptan in human isolated basilar and coronary arteries.

The contractile actions of the novel high-affinity 5-hydroxytryptamine (5-HT(1B/1D)) ligand, frovatriptan (formerly VML 251/SB-209509) were investigated in human isolated basilar and coronary arteries in which the endothelium had been removed. Basilar arteries were obtained post mortem, and coronary arteries were obtained from patients undergoing heart transplant (recipient) or from donor hearts that were not suitable for transplant. Frovatriptan was a potent contractile agent in isolated basilar artery with a -log mean effective concentration (EC50) value of 7.86 +/- 0.07 and intrinsic activity of 1.25 +/- 0.10 relative to 5-HT (n = 4). Frovatriptan was 8.5-fold more potent than sumatriptan, which produced a -log EC50 value of 6.93 +/- 0.09 and intrinsic activity 11.1 +/- 0.08 relative to 5-HT (n = 4). In coronary arteries, frovatriptan produced contraction with -log EC50 values of 7.38 +/- 0.12 and 7.81 +/- 0.2 in recipient (n = 7) and donor (n = 3) arteries, respectively. The relative degree of contraction of frovatriptan was lower than that of 5-HT, with relative intrinsic activities of 0.42 +/- 0.06 and 0.40 +/- 0.09, respectively. Sumatriptan produced contraction of human recipient and donor arteries with -log EC50 values (intrinsic activity) of 6.57 +/- 0.13 (0.79 +/- 0.27; n = 6) and 7.35 (1.41; n = 2), respectively. Furthermore, marked bell-shaped responses were apparent for frovatriptan in coronary arteries, with relaxation occurring at concentrations >6 microM in some tissues. In contrast, no bell-shaped concentration-response curves were apparent for sumatriptan or 5-HT. Threshold concentrations for frovatriptan-induced contractions were also different between basilar (>2 nM) and coronary arteries (>20 nM). No separation of threshold activity was observed with sumatriptan or 5-HT. These data show that frovatriptan produces constriction of human isolated basilar and coronary arteries. However, frovatriptan produces a complex pharmacologic response in the coronary artery, with threshold contractile activity requiring approximately 10-fold greater concentrations of agonist than in the basilar artery. Frovatriptan also shows a differential pharmacologic profile compared with sumatriptan in coronary arteries, with reversal of tone predominating at high concentration.

Oxidation of crotyl alcohol using Ti-β and Ti-MCM-41 catalysts

A comparative study of the oxidation of the crotyl alcohol using hydrogen peroxide and tert-butyl hydroperoxide as oxidants with TS-1,Ti-beta, Ti-Al beta, Ti-MCM-41, Ti-Al-MCM-41 and Ti-grafted-MCM-41 as catalysts is described and discussed. With hydrogen peroxide as oxidant, significant Ti-leaching is observed with all the catalysts except TS-I (Ti-Al beta > Ti-grafted-MCM-41 > Ti-MCM-41 > Ti beta >Ti-Al-MCM-41 much greater than TS-I). For Ti-Al beta, Ti-grafted- MCM-41 and Ti-Al-MCM-41, initial heterogeneously catalysed formation of the epoxide was observed. However, the formation of a Ti-species in solution is shown to contribute to competing homogeneously catalysed formation of ether diols and triol. Using tert-butyl hydroperoxide as oxidant the Ti-leaching was minimised and selective epoxide formation was observed with Ti-beta, Ti-Al beta and Ti-MCM-41 as heterogeneous catalysts, although, with Ti-Al beta, the ether diols and triol products dominated due to acid catalysed solvolysis of the epoxide

Influence of sulphur poisoning of copper/alumina catalyst on the selective hydrogenation of crotonaldehyde

Abstract The effect of the presence of sulphur on the activity and selectivity of a Cu/Al 2 O 3 catalyst has been examined by selective hydrogenation of an α, β-unsaturated aldehyde, crotonaldehyde, at different reaction conditions. Cu/Al 2 O 3 in the absence of sulphur poisons produced preferentially 1 -butanol, whereas catalysts pre-dosed with a suitable amount of thiophene, shifted the product distribution towards formation of crotyl alcohol. The formation of crotyl alcohol under these conditions is favoured at low conversions and low temperature, and the maximum selectivity of 64% crotyl alcohol was achieved at a reaction temperature of 80° C.

N-oxidation of pyridines by hydrogen peroxide in the presence of TS-1

In the production of aromatic N-oxides using the oxidation of N-containing heterocyclic aromatic substrates with H2O2 as oxidant, the non-catalysed homogeneous oxidation is found to play an important part in the overall reaction. In addition, when TS-1 is used as a catalyst, there are many potential competitive interactions between the catalyst, the reactants and the products, which limit the effectiveness of the catalyst. It is concluded that the use of TS-1 and other microporous catalysts for the heterogeneous N-oxidation of pyridine and substituted pyridines needs to be interpreted with caution.

Heterogeneous aziridination of alkenes using Cu2+ exchanged zeolites

Abstract Copper-exchanged zeolite Y (CuHY) is found to be a highly effective heterogeneous catalyst for the aziridination of alkenes using ( N -( p -tolylsulfonyl)imino)phenyliodinane (PhI=NTs) as the nitrogen source: Download full-size image Exchange of zeolite Y with other cations (Ag + , Co 2+ , Fe 3+ , Mg 2+ , Ni 2+ , Zn 2+ ) was found to be ineffective and the yield of the aziridine was lower than that obtained if no catalyst was present. This is considered to be due to the ability of these metals to catalyze the breakdown of the PhI=NTs reagent into iodobenzene and toluene sulfonamide. Modification of the CuHY catalyst with bis(oxazolines) leads to the preparation of the first heterogeneous enantioselective aziridination catalyst and the results showing the effect of temperature and modifier concentration are described and discussed. The optimum reaction conditions for the aziridination of styrene are found to be using acetonitrile solvent at −10°C with a Cu 2+ : bis(oxazoline) ratio of 2:1, and under these conditions, e.e. of 34–35% have been observed. The catalyst can be recovered and reused without significant loss of catalyst performance.