Showing papers on "Styrene oxide published in 1999"

Engineering of a Stable Whole-Cell Biocatalyst Capable of (S)-Styrene Oxide Formation for Continuous Two-Liquid-Phase Applications

Abstract: Recombinant strains of Pseudomonas putida KT2440 carrying genetic expression cassettes with xylene oxygenase- and styrene monooxygenase-encoding genes on their chromosomes could be induced in shaking-flask experiments to specific activities that rivaled those of multicopy-plasmid-based Escherichia coli recombinants. Such strains maintained the introduced styrene oxidation activity in continuous two-liquid-phase cultures for at least 100 generations, although at a lower level than in the shaking-flask experiments. The data suggest that placement of target genes on the chromosome might be a suitable route for the construction of segregationally stable and highly active whole-cell biocatalysts.

Biomonitoring of occupational exposure to styrene in a plastics lamination plant

Abstract: A comprehensive approach to biological monitoring of 44 workers occupationally exposed to styrene in a hand lamination plant was performed by using several end-points: styrene in workplace air, styrene in exhaled air, styrene in blood, DNA strand breaks (SBs) and oxidised bases in mononuclear leukocytes, chromosomal aberrations in lymphocytes, immune parameters and genotyping of polymorphic genes of some xenobiotic-metabolizing enzymes (CYP 1A1, EPHX, GSTM1 and GSTP1). We found a significantly higher number of DNA SBs, measured by a modified comet assay, in mononuclear leukocytes of the styrene-exposed workers compared with results from 19 unexposed controls (P<0.001). A fairly strong correlation was observed between SBs and years of exposure (P<0.001, r=0.545). The styrene-exposed workers also showed a significantly increased frequency of chromosomal aberrations (P<0.0001 for highly exposed group, P<0.004 for medium-exposed group, and P=0.0001 for low-exposed group). The proliferative response of T-lymphocytes stimulated with concanavalin A was significantly suppressed in people exposed to styrene (P<0.05). We recorded a significant increase of the percentage of monocytes in differential white blood cell counts in the exposed group (P<0.05). Using flow cytometry, we found an increased expression of adhesion molecules CD62L, CD18, CD11a, CD11b, CD49d and CD54 in the exposed workers as compared with the control group (P<0.05).

Mutation of Tyrosine Residues Involved in the Alkylation Half Reaction of Epoxide Hydrolase from Agrobacterium radiobacter AD1 Results in Improved Enantioselectivity

Abstract: Enantiomerically pure epoxides (oxiranes) are uniquely suited building blocks for synthetic purposes.1 Such epoxides are often prepared by means of remarkably effective synthetic catalysts.2 There are, however, few enzymatic routes in the repertoire.3 We have studied the enzyme mediated kinetic resolution of readily available racemic epoxides by selective hydrolysis of one enantiomer to the 1,2-diol, a process for which a synthetic catalyst has recently also been developed.4 Epoxide hydrolases that perform this conversion have been found in various organisms.5 An attractive enzyme is the recombinant epoxide hydrolase from Agrobacterium radiobacter AD16 that can be produced in large amounts and which has good potential for the kinetic resolution of styrene oxides.7 Here we report novel aspects of the catalytic mechanism of the enzyme and a mechanism-based approach that has led to the first site-specific mutant of an epoxide hydrolase that has improved characteristics in kinetic resolutions. The epoxide hydrolase from A. radiobacter AD18 belongs to the R/â-hydrolase fold family and contains a catalytic triad in the active site.9 The catalytic mechanism involves two discrete chemical steps. The first is an SN2 nucleophilic attack by an Asp107 carboxylate oxygen on the least-hindered carbon atom of the epoxide, resulting in a covalent ester intermediate (Figure 1). In the second step, the ester intermediate is hydrolyzed by a water molecule that is activated by the Asp246-His275 pair.8 The chemical opening of an epoxide is facilitated by an acidic functional group that interacts with the ring oxygen. Such an activation likely also takes place in epoxide hydrolases. 10 Earlier speculations were made that the proton donor could be a lysine residue, but evidence in support of this is scant.8,9c,11 We observed from crystallographic data for epoxide hydrolase from A. radiobacter AD112 that Tyr152 and Tyr215 are positioned close to the nucleophilic Asp107 in a manner such that their phenolic hydroxyl groups could be proton donor. No backbone amides or other acid groups are present that can serve as oxyanion hole or as proton donor during ring opening. A mechanistical role for Tyr215 was supported by a sequence alignment of known epoxide hydrolase sequences, which revealed that this tyrosine residue is absolutely conserved in the C-terminal part of the cap domain. This is remarkable considering that the overall similarity between various epoxide hydrolase sequences is often less than 20%, and indicates an important role for this residue. The tyrosine residue is conserved within a short stretch of sequence that is different for soluble and microsomal epoxide hydrolases, namely N-W/Y-Y-R and R-F/Y-Y-K, respectively. Sequence alignments were particulary poor in the N-terminal part of the cap domain where Tyr152 is located, and only alignments done by hand indicated that a second tyrosine might be present in the other soluble epoxide hydrolases. To investigate the role of Tyr215 and Tyr152, we constructed mutant enzymes in which the tyrosine was replaced by a phenylalanine13 and the resulting mutant enzymes were expressed and purified to homogeneity.14 The Tyr215Phe mutant showed a 100to 1000-fold increase of the Km for both enantiomers of styrene oxide (SO) and p-nitrostyrene oxide (pNSO), a strong decrease of the kcat for the (S)-enantiomers, and a small decrease of the kcat for the (R)-enantiomers (Table 1).15 Mutation of Tyr152 to Phe resulted in an enzyme that had an even higher Km value for (R)-SO than the Tyr215Phe mutant whereas the kcat value again remained in the same order of magnitude as the value for wildtype enzyme (Table 1). The similar changes in the steady-state kinetics of the Tyr215Phe and the Tyr152Phe mutant compared to wild-type enzyme indicate that both tyrosines perform similar roles in the kinetic mechanism of epoxide hydrolase. A mutant * Address correspondence to this author. † Department of Biochemistry. ‡ Department of Organic and Molecular Inorganic Chemistry. § BIOSON Research Institute and Laboratory of Biophysical Chemistry. (1) Besse, P.; Veschambre, H. Tetrahedron 1994, 50, 8885. (2) (a) Jacobsen, E. N. In ComprehensiVe Organometallic Chemistry II; Wilkinson, G., Stone, F. G. A., Abel, E. W., Hegedus, L. S., Eds.; Pergamon: New York, 1995; Vol. 12, Chapter 11.1. (b) Johnson, R. A.; Shareless, K. B. Catalytic Asymmetric Synthesis; Ojima I., Ed.; VCH Publishers: New York, 1993; p 103. (c) Jacobsen, E. N. Catalytic Asymmetric Synthesis; Ojima, I., Ed.; VCH Publishers: New York, 1993; p 159. (3) Archelas, A.; Furstoss, R. Annu. ReV. Microbiol. 1997, 51, 491. (4) For an example with a transition metal catalyst see: Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936. (5) (a) Archer, I. V. J. Tetrahedron 1997, 53, 15617. (b) Faber, K.; Mischitz, M.; Kroutil, W. Acta Chem. Scand. 1996, 50, 249. (c) Archelas, A.; Furstoss, R. Tibtech 1998, 16, 108. (6) Jacobs, M. H. J.; van den Wijngaard, A. J.; Pentenga, M.; Janssen, D. B. Eur. J. Biochem. 1991, 202, 1217. (7) Lutje Spelberg, J. H.; Rink, R.; Kellogg, R. M.; Janssen, D. B. Tetrahedron: Asymmetry 1998, 9, 459. (8) Rink, R.; Fennema, M.; Smids, M.; Dehmel, U.; Janssen, D. B. J. Biol. Chem. 1997, 272, 14650. (9) (a) Lacourciere, G. M.; Armstrong, R. N. J. Am. Chem. Soc. 1993, 115, 10466. (b) Tzeng, H.-F.; Laughlin, L. T.; Armstrong, R. N. Biochemistry 1998, 37, 2905. (c) Laughlin, L. T.; Tzeng, H.-F.; Lin, S.; Armstrong, R. N. Biochemistry 1998, 37, 2897. (10) Moussou, P.; Archelas, A.; Baratti, J.; Furstoss, R. J. Org. Chem. 1998, 63, 3532. (11) Beetham, J. K.; Grant, D.; Arand, M.; Garbarino, J.; Kiyosue, T.; Pinot, F.; Oesch, F.; Belknap, W. R.; Shinozaki, K.; Hammock, B. D. DNA Cell Biol. 1995, 14, 61. (12) Nardini, M.; Ridder, I. S.; Rozeboom, H. J.; Kalk, K. H.; Rink, R.; Janssen, D. B.; Dijkstra, B. W. J. Biol. Chem. 1999, 274, 14579. (13) The Tyr215Phe and the Tyr152Phe mutants of epoxide hydrolase were constructed as described before.8 The primers 5′-caactacttccgtgccaac-3′ and 5′-gagtcgtggttctcgcaattcc-3′ (mutated codons are underlined) were used for constructing the Tyr215Phe mutant and the Tyr152Phe mutant, respectively. Subsequently, the mutated epoxide hydrolase genes were sequenced. (14) The mutant and wild-type enzyme were overexpressed in E. coli BL21(DE3) and purified as described before.8 The enzymes were stored in TEMAG buffer at 4 °C and remained fully active for at least two month. (15) The steady-state parameters kcat and Km for styrene oxide (SO) and p-nitrostyrene oxide (pNSO) were obtained from progress curves, using an amount of enzyme sufficient to complete the reaction within 20 min.8 SO was analyzed by gas chromatography.8 Substrate depletion curves for pNSO were recorded in TE buffer at 30 °C on a Kontron Uvikon 930 UV/VIS spectrophotometer. The reaction was started by the addition of a stock solution of pNSO in acetonitrile to the cuvette with the enzyme solution to a final concentration of 1% acetonitrile. By using the extinction coefficients for pNSO ( 310 ) 4289 M-1 cm-1) and the corresponding diol ( 310 ) 3304 M-1 cm-1), the recorded traces were directly fitted with the Michaelis-Menten equation to obtain kcat and Km values. Figure 1. Schematic representation of the first step of the reaction mechanism of epoxide hydrolase. 7417 J. Am. Chem. Soc. 1999, 121, 7417-7418

Copolymerization and Terpolymerization of CO2 and Epoxides Using a Soluble Zinc Crotonate Catalyst Precursor

Abstract: A soluble catalyst precursor derived from the reaction of zinc bis(trimethylsilyl)amide, Zn[N(SiMe3)2]2, and crotonic acid has been found to be extremely active toward the copolymerization of cyclohexene oxide and carbon dioxide with turnover frequencies approaching 35 g/g of Zn/h at 80 °C. This catalyst precursor was also demonstrated to be an efficient terpolymerization catalyst when propylene oxide or styrene oxide was added to the cyclohexene oxide/CO2 feed. Extensive characterization of the metal complex proved difficult, but 31P NMR studies have shown that only 10% of the anticipated epoxide binding sites were available for catalysis. This suggests that the complex has several structures at its disposal, only one of which is conducive to copolymerization.

Nafion-H catalysed isomerization of epoxides to aldehydes and ketones

Abstract: Nafion-H, a perfluorinated resin sulphonic acid was found to be an efficient and simple catalyst for the isomerization of epoxides to ketones or aldehydes depending on the nature of the substituents on the epoxide carbons. The reaction is very straightforward giving the products in high yield. Isoamylene oxide (5) gave isopropyl methyl ketone (3) and styrene oxide and its derivatives (7a–g) gave phenylacetaldehyde and its derivatives (8a–g).

Challenges in capturing oxygenase activity in vitro

Abstract: Biocatalysis using oxygenase or desaturase enzymes has the potential to add value to native fats and oils by adding oxygen, hydroxyl groups, or double bonds to create regio- and/or stereospecific products. These enzymes are a subset of the large class of oxidoreductase enzymes (from EC subgroups 1.13 and 1.14) involved with biological oxidation and reduction. In vitro biocatalytic processing using these enzymes is hampered by the high cost of the stoichiometric cofactors. This article reviews recent progress in developing in vitro redox enzyme biocatalysis for commercial-scale syntheses. Coenzyme recycling and electrochemical redox cycling as methods for cofactor regeneration are described and commercial applications indicated. Direct charge transfer without use of mediators is described as the cleanest way of introducing the reducing power into the catalytic cycle. Our electrochemically driven cytochrome P450cam bioreactor is discussed as an example of direct charge transfer to a redox protein. Site-directed mutagenesis in the active site of the P450cam monooxygenase greatly improved performance for the conversion of the nonnative substrate, styrene to styrene oxide. This epoxidation reaction was also shown to give a single product (styrene oxide) in the bioelectrochemical reactor when the diatomic oxygen co-substrate was managed properly.

The preparation of β-substituted amines from mixtures of epoxide opening products via a common aziridinium ion intermediate

Abstract: Here we describe a one-pot synthesis of a series of β-substituted amines as single enantiomers from an initial regioisomeric mixture of styrene oxide ring-opening products. We also report the isolation and characterization of a key β-chloro intermediate and provide additional insight into the mechanism of the reported alkylations. These results require that the reaction proceeds through a common aziridinium ion intermediate on two separate occasions in order to account for the observed overall net retention of configuration in proceeding from ( S )-styrene oxide to the desired β-substituted amine products.

Selective oxidation of alkenes catalysed by ruthenium(II) complexes containing coordinated perchlorate

Abstract: Ruthenium(II) perchlorate complexes, [Ru(dppm)3(ClO4)]ClO4 1, [Ru(dppe)3(ClO4)]ClO4 2, and [Ru(dpae)3(ClO4)]ClO4 3, catalyse the selective homogeneous oxidation of alkenes with TBHP and H2O2 as oxidizing agents. Oxidation of cyclohexene with TBHP gave 2-cyclohexene-1-ol, 2-cyclohexenone and 1-(tert-butylperoxy)-2-cyclohexene. The homogeneous liquid phase oxidation of cyclohexene with TBHP shows appreciable solvent effect. Styrene on oxidation with TBHP gave benzaldehyde as the major product and styrene oxide as the minor product. Oxidation with H2O2 is radical-initiated and gives low conversion to products. TBHP and H2O2 are compared for their oxidizing ability and TBHP is more effective than H2O2 as an oxidizing agent. Linear and long chain alkenes are not efficiently oxidized. Cyclooctene and trans-stilbene are oxidized to the corresponding epoxides.

Phosphoric acid esters and their use as dispersing agent

Abstract: Phosphate esters of amphiphilic block copolymers consisting of poly(alkyl)styrene or polystyrene oxide segments and polyalkylene oxide segments. Phosphate esters of formula (I) are new: R = (IIa) or (IIb); x = 1 or 2; n = 2-18; m, o = 2-100; k = 2-4; R = H or alkyl (optionally substituted with other functional groups); R' = alkyl, alkaryl, alkenyl or sulfopropyl. Independent claims are also included for: (a) the production of (I) by (A) reacting an omega -hydroxy-functional oligo- or poly-(alkyl)styrene with an alkylene oxide to give a poly(alkyl)styrene-polyalkylene oxide block copolymer and then esterifying this by reaction with a phosphate ester-forming compound so that up to 100% of the terminal OH groups undergo reaction and the phosphorus atoms are mono- and/or di-esterified; or (B) reacting a phosphate ester-forming compound as above with a polystyrene oxide-polyalkylene oxide block copolymer obtained from a monofunctional starting alcohol by addition of styrene oxide and alkylene oxide to give segments of the required chain length in the required sequence; and (b) pigment preparations and aqueous pastes based on inorganic or organic pigments or dyes, containing 1-100 wt% ester (I) as dispersant (based on pigment or dye), especially aqueous carbon black paste containing 10-100 wt% (I).

Conformational analysis, Part 31.1 A theoretical and lanthanide induced shift (LIS) investigation of the conformations of some epoxides

Abstract: An improved LIS technique, using Yb(fod)3 to obtain the paramagnetic induced shifts of all the spin ½ nuclei in the molecule, together with complexation shifts obtained by the use of Lu(fod)3, has been used to investigate the conformations of a group of epoxides. These are cis (1) and trans (2) stilbene oxide, cyclopentene oxide (3), cyclohexene oxide (4), cycloheptene oxide (5), propene oxide (6) and styrene oxide (7).The LIRAS3 complexation model involving two symmetric lone pairs on the oxygen atom was used for the symmetric compounds but, for the unsymmetric compounds, a more complex unsymmetric complexation model (HARDER) was found to be necessary. The calculated LIS for styrene oxide and cis- and trans-stilbene oxide were in excellent agreement with the observed data for both the molecular mechanics (MM) and the ab initio geometries with the phenyl ring dihedral angles optimised.In styrene oxide and trans-stilbene oxide the phenyl rings are approximately perpendicular to the oxirane ring, in agreement with the conformation in the solid state and with the theoretical calculations. In cis-stilbene oxide steric repulsions between the phenyl rings splay them apart so that they are now exo to the oxirane ring. Again the LIS analysis is in good agreement with the theoretical calculations.Both the LIS data and the modelling studies agree that cyclopentene oxide is in a boat conformation with an angle of pucker of ca. 30° and that cyclohexene oxide is in a half-chair conformation with C4 and C5 displaced from the ring plane.The LIS analysis of cycloheptene oxide gave good agreement for two equilibrating chair conformations with an endo/exo ratio of 70∶30, in excellent agreement with low temperature NMR data.The accurate reproduction of the LIS data provides an unambiguous method of assigning the proton chemical shifts of the individual methylene protons in the cyclic epoxides, which are not easily available by any other technique.

Formation of deaminated products in styrene oxide reactions with deoxycytidine.

Abstract: The reaction of racemic styrene oxide with deoxycytidine under aqueous conditions was studied. The four principal products isolated were a pair of diastereomeric N(4)-(2-hydroxy-1-phenylethyl)deoxycytidines ( approximately 20% of the products) and a pair of diastereomeric 3-(2-hydroxy-2-phenylethyl)deoxyuridines ( approximately 80% of the products). Reactions with optically active styrene oxides allowed the configurations of the 3-(2-hydroxy-2-phenylethyl)deoxyuridines to be assigned, and these structures were confirmed by an independent synthesis from deoxyuridine. Also, it was possible to tentatively assign the configurations of the N(4)-(2-hydroxy-1-phenylethyl)deoxycytidines that had undergone some racemization during the reaction (the ratio of the retained to inverted configuration of the products was approximately 1:7).

Epoxidation of styrene with TBHP/O2 over ferrierite (FER) type molecular sieves

Abstract: Epoxidation of styrene over vanadium silicalite with ferrierite (FER) type topology is undertaken. Influence of temperature, pressure, various solvents and solvent to substrate mole ratio was investigated. Conversion increased with increase in temperature and pressure. Solvent to substrate mole ratio is found to play a crucial role in increasing the conversion and selectivity. Catalytic activity of V‐FER was compared with those of Ti‐FER, TS‐1 and Fe‐FER. In the case of V‐ and Ti‐ferrierite analogs, styrene oxide was the major product, whereas phenylacetaldehyde was the major product in the case of TS‐1. The catalyst could be recycled after washing by a suitable solvent such as acetone and showed no significant loss in catalytic activity.

Effect of styrene on monoamine oxidase B activity in rat brain

Abstract: Previous studies have indicated that workers exposed to styrene present a decreased activity of platelet monoamine oxidase B (MAO B), suggesting that this biochemical assay may represent a biomarker for styrene-induced neurotoxicity. This study was undertaken to determine whether exposure to styrene would cause changes in MAO B activity in the target organ--the brain. Groups of rats were exposed to styrene by inhalation at concentrations of 300 ppm for 4 wk or 50 ppm for 13 wk. Both treatments caused significant decreases of MAO B activity in several brain areas, while MAO A activity was not affected. Decreases in MAO B activity were also found in brainstem of rats given styrene (400 mg/kg) or styrene oxide (100 mg/kg) by i.p. injection for 2 wk. Styrene, styrene oxide, and other styrene metabolites (mandelic acid, phenylglyoxylic acid, and styrene glycol) had no direct inhibitory effect on brain MAO B activity when tested in vitro. These results indicate that exposure to low concentrations of styrene alters MAO B activity in rat brain, suggesting that the observed changes in human platelets may reflect alterations in the nervous system.

Polymerization of styrene oxide catalyzed by a diethylzinc/?-pinene oxide system

Abstract: Styrene oxide (SO) was polymerized with a diethylzinc/α-pinene oxide (ZnEt2/α-PiO) catalyst system under various conditions. Polystyrene oxide (PSO) thus obtained had a regular head-to-tail and isotactic structure. The number-average molecular weight reached 4.07 × 104, and the molecular weight distribution was 5.7 (Mw/Mn). The glass-transition temperature of PSO was about 47 to 50 °C, depending on the molecular weight. The molar ratio of ZnEt2 to α-PiO, 2 : 1, led to a high molecular weight of PSO in an 89.2% yield within 72 h. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 4640–4645, 1999

Bactericidal detergent composition

Abstract: PROBLEM TO BE SOLVED: To obtain a bactericidal detergent composition which exhibits an effective detergency to both inorganic dirt and organic dirt by incorporating peracetic acid, acetic acid, hydrogen peroxide, and a surfactant into the same. SOLUTION: This composition is prepared by dissolving 0.3-1.5 wt.% peracetic acid, 2-20 wt.% acetic acid, 4-12 wt.% hydrogen peroxide, and 1-20 wt.% surfactant. The surfactant is preferably a nonionic surfactant represented by the formula: R1O-(R2-O)n-H, wherein R1 is a hydrocarbon group; R2 is alkylene; and n is 1 or higher. The moiety represented by (R2-O)n in the formula can be formed by the addition polymerization of an alkylene oxide or the like such as ethylene oxide, propylene oxide, butylene oxide, an α-olefin oxide or styrene oxide. In forming the (R2-O)n moiety, R2 is determined by the kind of the alkylene oxide or the like. Preferably, 50-100 mol% of the (R2-O)n moiety is accounted for by oxyethylene units, and the degree of polymerization (n) is 1-20.

Regulatory nature of β-cyclodextrin in selective ring-opening during reduction of styrene oxide

Abstract: The cleavage of styrene oxide by different reagents like Raney nickel, palladium–carbon and sodium borohydride in the presence of β-cyclodextrin and its derivatives like β-CD-epichlorohydrin (β-CD-polymer) and heptakis-2,6-di-O-methyl-β-cyclodextrin (DMβ-CD) showed distribution in formation of ethylbenzene, 1-phenylethanol and 2-phenylethanol. Formation of deoxygenated products like styrene and ethylbenzene were suppressed by β-CD and its derivatives under hydrogenation over Raney nickel favouring increase in proportion of 2-phenylethanol. β-CD and its derivatives regulated increase in formation of 1-phenylethanol under reduction by Pd–C and NaBH4. Observed selectivities have been correlated to arise directly from the disposition adopted by styrene oxide inside the β-CD cavity, the nature and manner of which has been arrived at from the spectroscopic studies (UV and NMR) of inclusion.

Stabilization of fluorine-containing ether and premix for foaming urethane

Abstract: PROBLEM TO BE SOLVED: To stabilize a fluorine-containing ether in the case of the storage of the fluorine-containing ether or a urethane-foaming premix containing water essentially without causing the destruction of ozonosphere by adding a specific stabilizing agent to a specific fluorine-containing ether. SOLUTION: A fluorine-containing ether can be stabilized by adding (A) at least one kind of compound selected from 1,2-butylene oxide, styrene oxide, propylene oxide, etc., to (B) a fluorine-containing ether composed exclusively of C, H, F and O, having at least one H atom, 2-6 C atoms and 4-11 F atoms in one molecule (e.g. CHF2 CF2 OCH3 , CH2 FCF2 OCHF2 and CF3 CHFOCHF2 ). The amount of the component A is usually 1 ppm to 2% based on the component B.

Synthesis of 3-alkylated triacetonamine derivatives

Abstract: Reaction of a lithiated imine derivative of 2,2,6,6-tetramethyl-4-piperidone (triacetonamine, 1) with activated or less reactive alkyl halides or styrene oxide and subsequent hydrolysis afforded 3-alkylated triacetonamine derivatives. Thus, 3-benzyl-2,2,6,6-tetramethyl-4-piperidone (3), 3-(n-butyl)-2,2,6,6-tetramethyl-4-piperidone (4), 3-(3-chloropropyl)-2,2,6,6-tetramethyl-4-piperidone (5), 2,2,3,6,6-pentamethyl-4-piperidone (6) and two diastereomers of 3-(2-hydroxy-2-phenylethyl)-2,2,6,6-tetramethyl-4-piperidone (7) were prepared in 26–53% yield. Reaction of the imine anion derived from 1 with benzyl bromide to give 3 has to be performed at low temperatures in order to avoid a competing proton transfer. No reaction at the unprotected piperidine nitrogen was observed.

Continuous process for the production of 2-phenylethanol comprises hydrogenation of a solution containing styrene oxide with hydrogen in the presence of a monolithic metal supported catalyst.

Abstract: A continuous process for the production of 2-phenylethanol from styrene oxide by hydrogenation of a solution containing styrene oxide and 2-phenylethanol with hydrogen in the presence of a catalyst comprising a monolithic supported catalyst having a metallic support. An Independent claim is included for a device for carrying out the process, comprising a reactor (1) containing the catalyst (2) having an inlet at the base of the reactor by which the reaction solution and hydrogen enters the reactor via liquid-spray gas compressor (5). The reaction mixture leaves the reactor by the outlet (6) to a separator (7) from which the product is recovered (14) and the reaction solution containing the unreacted material is recirculated by means of the pump (8), heat exchanger (9) and liquid-spray gas compressor (5). Fresh reactant is introduced by means of (3). Unreacted hydrogen from the separator (7) is recirculated via a gas recirculation loop comprising pipes (11) and (13) and liquid-spray gas compressor (5). Fresh hydrogen is added by means of (4) and pressure is maintained by means of the gas outlet (12).