Synthesis and Reactions of Enantiopure Substituted Benzene cis‐Hexahydro‐1,2‐diols

Enantiopure cis‐dihydro‐1,2‐diol metabolites, obtained from toluene dioxygenase‐catalysed cis‐dihydroxylation of six monosubstituted benzene substrates, have been converted to their corresponding cis‐hexahydro‐1,2‐diol derivatives by catalytic hydrogenation via their cis‐tetrahydro‐1,2‐diol intermediates. Optimal reaction conditions for total catalytic hydrogenation of the cis‐dihydro‐1,2‐diols have been established using six heterogeneous catalysts. The relative and absolute configurations of the resulting benzene cis‐hexahydro‐1,2‐diol products have been unequivocally established by X‐ray crystallography and NMR spectroscopy. Methods have been developed to obtain enantiopure cis‐hexahydro‐1,2‐diol diastereoisomers, to desymmetrise a meso‐cis‐hexahydro‐1,2‐diol and to synthesise 2‐substituted cyclohexanols. The potential of these enantiopure cyclohexanols as chiral reagents was briefly evaluated through their application in the synthesis of two enantiomerically enriched phosphine oxides from the corresponding racemic phosphine precursors.     

Production of optically pure L-alanine by immobilized Pseudomonas sp. BA2 cells

The conditions for immobilizing the new L -aminoacylase-producing bacterial strain, Pseudomonas sp. BA2, by entrapment in κ-carrageenan gel, were investigated. The optimal gel concentration and cell load were determined. The addition of CoCl₂ and N-acetyl-L -alanine to the immobilizing matrix enhanced L -aminoacylase activity. The enzymatic properties of immobilized Pseudomonas sp. BA2 were investigated. Enzyme activity in immobilized cells was optimal at a pH of 6·5 using 0·15 mol dm⁻³ Tris–maleate buffer at 45°C. The presence of 0·7 mmol dm⁻³ CoCl₂ in the enzymatic reaction mixture improved L -aminoacylase activity. The immobilized cell preparation was used for the production of L -alanine from N-acetyl-DL -alanine in a batch reactor. Conversions of 100% were obtained using substrate concentrations ranging from 20 to 200 mmol dm⁻³. The reactor production was 0·74 mol h⁻¹ g cell⁻¹ dm⁻³ which is noticeably higher than that previously reported in the literature. © 1998 Society of Chemical Industry     

Enzymatic Hydrolysis of Cassava Starch into Maltose Syrup in a Continuous Membrane Reactor

This study deals with the use of a membrane reactor for the enzymatic conversion of cassava starch to maltose. The enzymes used were Maltogenase and Promozyme (Novo Nordisk). Maltogenase activity was unaffected after a 5 h incubation period at 65°C, but Promozyme was markedly heat-unstable even at 37°C. Batch hydrolysis of liquefied cassava starch (30% w/w) by Maltogenase and Promozyme resulted in a maximum degree of starch conversion to maltose of 72% (≈254 g dm⁻³ maltose). The conversion degree fell by 11% when no debranching enzyme was used. The residence time distribution of the ultrafiltration reactor (UFR) was that of an ideal continuously stirred tank reactor. Rejection of Maltogenase by Carbosep M4 membranes (MWCO: 50 kDa) was not total. The overall enzyme activity loss after a 5 h diafiltration period was 28%, however about half this loss appeared to be due to enzyme denaturation inside the reactor. During saccharification trials conducted in the UFR at a starch concentration of 30% (w/w), severe membrane fouling occurred. The average permeate fluxes obtained were 14 and 23 dm³ h⁻¹ m⁻² at constant transmembrane pressures of 100 and 200 kPa respectively. When the reactor was operated at a space-time of 4·2 h, the degree of starch conversion to maltose in the permeate rapidly stabilized around 55–56%. © 1997 SCI.     

Dynamic enzymatic resolution of Naproxen methyl ester in a membrane bioreactor

A lipase‐catalyzed enantioselective continuous hydrolysis process under in situ racemization of substrate using sodium hydroxide as catalyst was developed for the production of (S)‐Naproxen from racemic Naproxen methyl ester in an aqueous–organic biphase system. Use of a tubular silicone rubber membrane in the stirred tank reactor to separate the chemical catalytic racemization and biocatalytic resolution processes, served to avoid the key problem associated with conventional dynamic resolution, viz the incompatibility of in situ chemical racemization with the presence of a biocatalyst. To overcome product inhibition and to facilitate product recovery from the aqueous–organic emulsion containing substrate and lipase, a hydrophilic porous semipermeable membrane was used in the stirred tank reactor. Greater than 60% conversion of the racemate with an enantiomeric excess of product (ee_p) greater than 96% was obtained. In addition, transformation of Candida rugosa lipase (CRL) isoenzymes was observed in the reaction process. © 2001 Society of Chemical Industry     

Exploring the Biocatalytic Scope of Alditol Oxidase from Streptomyces coelicolor

The substrate scope of the flavoprotein alditol oxidase (AldO) from Streptomyces coelicolor A3(2), recombinantly produced in Escherichia coli, was explored. While it has been established that AldO efficiently oxidizes alditols to D ‐aldoses, this study revealed that the enzyme is also active with a broad range of aliphatic and aromatic alcohols. Alcohols containing hydroxy groups at the C‐1 and C‐2 positions like 1,2,4‐butanetriol (K_m=170 mM, k_cat=4.4 s⁻¹), 1,2‐pentanediol (K_m=52 mM, k_cat=0.85 s⁻¹) and 1,2‐hexanediol (K_m=97 mM, k_cat=2.0 s⁻¹) were readily accepted by AldO. Furthermore, the enzyme was highly enantioselective for the oxidation of 1,2‐diols [e.g., for 1‐phenyl‐1,2‐ethanediol the (R)‐enantiomer was preferred with an E‐value of 74]. For several diols the oxidation products were determined by GC‐MS and NMR. Interestingly, for all tested 1,2‐diols the products were found to be the α‐hydroxy acids instead of the expected α‐hydroxy aldehydes. Incubation of (R)‐1‐phenyl‐1,2‐ethanediol with ¹⁸O‐labelled water (H₂¹⁸O) revealed that a second enzymatic oxidation step occurs via the hydrate product intermediate. The relaxed substrate specificity, excellent enantioselectivity, and independence of coenzymes make AldO an attractive enzyme for the preparation of optically pure 1,2‐diols and α‐hydroxy acids.     

Acyl Migration Kinetics of Vegetable Oil 1,2-Diacylglycerols

The acyl migration kinetics of long-chain 1,2-diacylglycerol (1,2-DAG) to form 1,3-diacylglycerol (1,3-DAG) over the temperature range of 25–80 °C were examined using ¹H-NMR spectroscopy. Lipase-catalyzed ethanolysis of high-oleic sunflower oil, followed by a series of solvent extraction steps, generated high purity 1,2-DAG (0.93 mol fraction of the DAG content). The 1,2-DAG mole fraction of 0.32 at equilibrium was found to be insensitive to temperature, indicating that long-chain acyl group migration is neither endothermic nor exothermic. Determination of the temperature-dependent, first-order reaction kinetic parameters revealed a 1,2-DAG half life (t _1/2) of 3,425 h and 15.8 h at 25 and 80 °C, respectively. A comparison of 1,2-DAG with 2-monoacylglycerol indicated that there is no difference between the two in the potential energy state (ΔG ^‡) of their respective transitions states or cyclic intermediates. Product names are necessary to report factually on available data; however, the USDA neither guarantees nor warrants the standard of the product, and the use of the name by the USDA implies no approval of the product to the exclusion of others that may be suitable.     

Continuous Application of Polyglycerol‐Supported Salen in a Membrane Reactor: Asymmetric Epoxidation of 6‐Cyano‐2,2‐dimethylchromene

In the current work, suitability of hyperbranched polyglycerol as a high loading catalyst support is demonstrated. A polyglycerol‐supported manganese‐salen complex (chemzyme) is applied as a homogeneous catalyst in the epoxidation of 6‐cyano‐2,2‐dimethylchromene. The recyclability of the corresponding catalyst was investigated in repetitive batch experiments as well as a continuous operation of the reaction in an ultrafiltration membrane reactor. An enhanced stability of the catalyst in repetitive batches was observed as a result of immobilization whereby the total turnover number increased from 23 in a single batch to 80 in four repetitive batches. To enable continuous operation, a continuously operated, stirred tanked reactor (CSTR) was equipped with an ultrafiltration membrane (MPF‐50) and a retention of 98% was determined. The continuous chemzyme membrane reactor was operated over the course of 20 residence times. After approximately 12 residence times, the steady state was reached yielding 70% conversion as well as an enantiomeric excess up to 92%. A space‐time yield (sty) of 458 g L ⁻¹ d⁻¹ and a turnover frequency (TOF_reaction) of up to 18 h⁻¹ was reached in the steady state. It was determined that the total turnover number (TTN) was enhanced by a factor of 10 from 24 (batch) up to 240 for 20 residence times in CSTR operation.     

A three‐phase fluidized bed reactor in the combined anaerobic/aerobic treatment of wastewater

Aerobic degradation or polishing is an essential step in the combined anaerobic/aerobic treatment of wastewater. In this study, a type of porous glass beads was used for immobilization of microbial cells in a three‐phase aerobic fluidized bed reactor (AFBR) with an external liquid circulation. The effects of superficial gas and liquid velocities on bed expansion, solid and gas hold‐ups and specific oxygen mass transfer rate, k_La, were investigated. A tracer study showed that the mixing and flow pattern in the 8 dm³ reactor could be simulated by a non‐ideal model of two continuous stirred tank reactors (CSTRs) in series. By treating an effluent from an upflow anaerobic sludge blanket (UASB) digester, the distribution of suspended and immobilized biomass in the reactor as well as the kinetics of COD removal were determined. The specific oxygen mass transfer rate, k_La, at a superficial gas velocity of 0.7 cm s⁻¹ dropped by about 30% from 32 h⁻¹ in tap water to 22 h⁻¹ after a carrier load of 15% (v/v) was added. The measured k_La further dropped by about 20% to 18 h⁻¹ in the wastewater, a typical value of the bubbling fermenters with no stirring. Compared with the aerobic heterotrophs under optimum growth conditions, the microbes in this reactor which was fed with anaerobic effluent plus biomass behaved like oligotrophs and showed slow specific COD removal rates. This might be attributed to the presence of a significant amount of obligate anaerobes and facultative organisms in the aerobic reactor. This was confirmed by a relatively low intrinsic oxygen uptake rate of the microbial population in the reactor, 94 mg O₂ dm⁻³ h⁻¹ or 19 mg O₂g VS⁻¹ h⁻¹. © 1999 Society of Chemical Industry     

Poisoning of Pd–carbon catalysts by sulphur,chloro and heavy metal compounds in liquid phase hydrogenation of o-nitrophenol to o-aminophenol

The poisoning of Pd–carbon (4·1% Pd) catalysts by thiophene, dichloroethane, mercuric chloride and lead, zinc and mercuric acetates at different concentrations (0–5000 g m⁻³) in the liquid phase hydrogenation of o-nitrophenol to o-aminophenol (at 308 K and H₂ pressure of 1508 kPa) in a three-phase stirred slurry reactor has been investigated. The hydrogenation activity of the catalyst is drastically reduced due to the presence of these poisons in the reaction mixture, even at a very low concentration of poison (20 g m⁻³). Among the poisons, mercuric acetate was found to be the most potent. © 1998 Society of Chemical Industry     

N,N‐diethyl dithiocarbamato group induced photografting of methyl methacrylate onto polyurethane

The N,N‐diethyl dithiocarbamato group present in a variety of compounds acts as an initiator in the photopolymerization processes. The photolability of this group is due to the cleavage of the C S bond by UV irradiation. N,N‐Diethyl dithiocarbamato‐(1,2)‐propane diol with a pendent N,N‐diethyl dithiocarbamato group was prepared from 3‐chloro‐(1,2)‐propane diol and sodium diethyl dithiocarbamate. A polyurethane macrophotoinitiator was then synthesized by a two‐step process, where N,N‐diethyl dithiocarbamato‐(1,2)‐propane diol was used as the chain extender. Other components used included 4,4′‐diphenylmethane diisocyanate and poly(propylene glycol) (molecular weight = 1000). The polyurethane thus synthesized had pendent N,N‐diethyl dithiocarbamato groups. This polyurethane macrophotoinitiator was then used to polymerize methyl methacrylate in a photochemical reactor (Compact‐LP‐MP 88) at 254 nm. The resulting graft copolymer, polyurethane‐g‐poly(methyl methacrylate), was freed from the homopolymer by a standard procedure. The graft copolymer was characterized by Fourier transform infrared spectroscopy, ¹H‐NMR spectroscopy, thermogravimetric analysis, differential scanning calorimetry, solution viscometry, and scanning electron microscopy. © 2008 Wiley Periodicals, Inc. J Appl Polym Sci, 2009     

Desulphurization of organic sulphur from coal by electron transfer process with Co2+ ion

This paper reports the results of desulphurization of organic sulphur from a subbituminous Meghalaya coal by the electron transfer process accomplished with the metal ion Co²⁺. The process was studied both in presence and absence of naphthalene which is used as an electron transfer agent. Temperature dependence on desulphurization unfolded that as the temperature is raised from 25 to 50 °C, there is increase in desulphurization performance. Model organic sulphur compounds study revealed that the desulphurization process is effective with aliphatic type of compounds. Infrared spectroscopic study revealed the release of easily removable sulphur compounds as the band intensities due to −SO and −SO₂ groups have declined considerably in their respective regions in the desulphurized coals. The degree of desulphurization is 28.5 wt.% in the presence of naphthalene and 24.6 wt.% in absence of naphthalene, both at 4 h and 50 °C. The sulphur extrusion process is continuous and application of a first-order kinetic model produced specific rate constants of the desulphurization reaction in the two systems, at different temperatures, which falls in the range of (1.3–2.9)×10⁻⁵ s⁻¹. The activation energy of the sulphur-loss reaction in the system containing naphthalene (26.8 kJ mol⁻¹) is about 12% lower than that of the system without naphthalene (30.6 kJ mol⁻¹). The frequency factor of the sulphur removal reaction in the systems have been found to be in the range of 0.8–3.2 s⁻¹, suggesting low amount of successful collisions and an associated type of reaction. The desulphurization reaction is nonspontaneous in nature, proceeds with the absorption of heat and there is reduction in the degree of disorderliness in the system as predicted by the transition state theory.     

Influence of 1,2 units content on the hydrogenation of polydienes by TSH

The influence of 1,2 vinyl content on hydrogenation of SBR and BR rubbers with high molecular weight by a noncatalytic method using p‐toluenesulfonylhydrazide (TSH) as reagent was investigated. Results show an increase of hydrogenation percentage with molar ratio of the reagents, temperature, and reaction time. The degree of hydrogenation depends strongly on the microstructure of the rubber mainly on the amount of 1,2 content. Infrared spectroscopy (FTIR) was used to confirm the microstructural characteristics of the hydrogenated rubbers. The degree of hydrogenation was determined by iodometry method and ¹H‐NMR analysis. The change in the thermal behavior of hydrogenated rubbers was followed by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), which showed a difference in flexibility chain and thermal stability. The kinetic studies demonstrate that the diimide reduction follows a first‐order reaction with respect to olefin substrate. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2011     

Aspergillus oryzae Lipase-Catalyzed Synthesis of Dioleoyl; Palmitoyl-Rich Triacylglycerols in Two Reactors

Dioleoyl; palmitoyl‐rich triacylglycerols (OPO‐rich TAG) were synthesized through Aspergillus oryzae lipase (AOL)‐catalyzed acidolysis of palm stearin with commercial oleic acid by a one‐step process in a stirred tank reactor and continuous packed bed reactor to evaluate the feasibility of using immobilized AOL. AOL was found to be valuable for the synthesis of OPO‐rich TAG when compared with commercial lipase from Thermomyces lanuginose (Lipozyme^® TL IM; Novozymes A/S, Bagsvaerd, Denmark). The C52 (triglycerides with a carbon number of 52, stands for OPO, OPL, LPL and their isomers) content of AOL was higher (45.65 %), and the intensity of treatment (IOT: lipase amount × reaction time/TAG amount) of AOL was just 6.25 % of that of Lipozyme^® TL IM under similar reaction conditions in the stirred tank reactor. Response surface methodology were used to optimize the reaction conditions of the AOL‐catalyzed acidolysis is reaction in the packed bed reactor. The optimal point for the set of experimental conditions generated were as follows: residence time 3.0 h; temperature 62.09 °C; substrate molar ratio 7.13 mol/mol. The highest C52 content obtained was 48.60 ± 2.36 %, with 57.46 ± 1.72 % total palmitic acid at the sn‐2 position and 74.21 ± 2.45 % oleic acid at the sn‐1,3 positions. The half‐life of AOL was 24 h in the stirred tank reactor and 140 h in the packed bed reactor. The immobilized AOL achieved similar conversion and selectivity to commercial lipases for the catalyzed synthesis of OPO‐rich TAG and may offer a cheaper alternative.     

Boronic Acid‐Catalyzed Selective Oxidation of 1,2‐Diols to α‐Hydroxy Ketones in Water

The activation of 1,2‐diols through formation of boronate esters was found to enhance the selective oxidation of 1,2‐diols to their corresponding α‐hydroxy ketones in aqueous medium. The oxidation step was accomplished using dibromoisocyanuric acid (DBI) as a terminal chemical oxidant or an electrochemical process. The electrochemical process was based on the use of platinum electrodes, methylboronic acid [MeB(OH)₂] as a catalyst and bromide ion as a mediator. Electro‐generated OH⁻ ions (EGB) at the cathode acted as a base and “Br⁺” ion generated at the anode acted as an oxidant. Various cyclic and acyclic 1,2‐diols as substrates were selectively oxidized to the corresponding α‐hydroxy ketones via their boronate esters by the two oxidative methods in good to excellent yields.

     

Lipolytic synthesis of optically active 1,2-dibutyryl-sn-glycerol. Identification of diglyceride by solvent-dependent specific rotation

The objective was to determine whether the initial pregastric lipase catalyzed hydrolysis of a triacylglycerol to 1,2(2,3)-diacylglycerol was a consequence of sn-specific hydrolysis. The identity of the reaction products for the enzyme-assisted hydrolysis and uncatalyzed acyl-transfer reaction sequence of tributyrylglycerol was assigned by ¹³C nuclear magnetic resonance. The optical activity of the product 1,2-dibutyryl-sn-glycerol (yield >50%, pH 6.5, 35°C, 13 min) was solvent dependent, being −2.92° (c ∼1.3, CHCl₃) and +3.32° (c ∼1.2, pyridine), and confirmation of sn-3 specificity by pregastric lipase was obtained.     

Effect of external mass transfer in a packed bed reactor system for a reversible enzyme reaction

A mathematical model was developed to describe the effect of external mass transfer for a packed-bed enzyme reactor in which a reversible, one-substrate, two-intermediate enzyme reaction took place. The model equation was applied to the analysis of an immobilized glucose isomerase reactor system. A Colburn-type mass transfer correlation was obtained from the Colburn j-factor versus Reynolds number plot: i.e., j_D = 0.045N_Re^−0.48. The values of mass transfer coefficient for the system under study ranged from 0.01 to 0.1 cm h⁻¹ depending on the substrate flow rate. Very good agreements were observed between the computer simulation using a plug flow reactor model with the derived mass transfer correlation and the experimental results obtained from the packed-bed reactor operation.     

A Stereocontrolled 1,2‐Addition Reaction of Tetrazoles with Alkyl Propiolates for the Synthesis of Highly Functionalized Enamines

A stereocontrolled 1,2‐addition reaction of 1‐aryl‐1H‐tetrazoles with alkyl propiolates for the synthesis of highly functionalized enamines was developed. In the presence of silver oxide (Ag₂O), the 1,2‐addition reaction generated (Z)‐N‐cyano enamines in good yields with exclusive formation of the Z‐isomers. Meanwhile, the 1,2‐addition reaction generated (E)‐N‐cyano enamines in the presence of Ag₂O and potassium carbonate (K₂CO₃) with high stereoselectivity and yields.     

Regioselective Copper‐Catalyzed Oxidative Cross‐Coupling of Imidazo[1,2‐a]pyridines with Methyl Ketones: An Efficient Route for Synthesis of 1,2‐Diketones

An efficient copper‐catalyzed oxidative coupling of imidazo[1,2‐a]pyridines with methyl ketones to directly generate structurally sophisticated 1,2‐dicarbonyl imidazo[1,2‐a]pyridine derivatives under oxidative conditions is described. The reaction proceeds in good yields using the environmental friendly molecular oxygen as the oxidant. ¹⁸O‐Labelling experiments unambiguously established that the oxygen of the dicarbonyl products originated from oxygen rather than from water.

     

Intensification principle of a new three-phase catalytic slurry reactor. Part I: Performance characterisation

This paper presents the concept and the performances of a mini horizontal stirred tank reactor, used for hydrogenation reaction. A simple analytical model based on characteristic times of heat and mass transfer illustrates the intensification principle and shows that the relevant intensification parameter is the mass to heat transfer characteristics times ratio. The proof of concept is made through a small scale reactor named RAPTOR^® (French acronym for Reactor with Polyvalent Rectilinear Stirred Reactor with Optimised Transfer). The mass transfer performances are measured and compared to conventional stirred tank reactor and other multiple impeller continuous reactors. In a following second paper, a comparative study is proposed to evaluate the eco-efficiency and the techno-economic advantages of a continuous process involving a RAPTOR^® versus a classical batch process based on a stirred reactor.     

Gold(I)‐Catalyzed Cascade for Synthesis of Pyrrolo[1,2‐a:2′,1′‐c]‐/Pyrido[2,1‐c]pyrrolo[1,2‐a]quinoxalinones

An efficient and convenient method was developed for the one‐pot construction of the complex polycyclic heterocycles pyrrolo[1,2‐a:2′,1′‐c]‐/pyrido[2,1‐c]pyrrolo[1,2‐a]quinoxalinones from two simple starting materials via a gold(I)‐catalyzed domino reaction. This strategy presents an atom economical and environmentally friendly transformation, in which two new C N bonds and one new C C bond are formed in a one‐pot reaction process.