CSTR和批式反应器中酶法拆分萘普生的比较

比较了批式反应器和连续流动搅拌反应器中酶动力学拆分萘普生的不同之处。从宏观反应器平衡角度,推导出了在ＣＳＴＲ中不同于在批式反应器中的酶立体选择性,产物对映体过量值和反应转化率的定量关系式,并通过脂肪酶催化的萘一甲酯的不对称水解反应得到了证实。     

First example of axial selectivity in the nucleophilic addition to (−)-menthone—addition of cyanomethyl lithium

The addition of cyanomethyl lithium to (−)-menthone at −78°C followed by 1.5 h stirring at room temperature and acidic workup produced exclusively the axial addition product, being the first example of preferred axial attack of an organometallic reagent to menthone. In the case of hydrolysis at −78°C after 0.5 h reaction time the equatorial addition product was isolated as the preferably formed isomer. The axial and equatorial cyanomethyl substituted menthol and neomenthol, respectively, were isolated in high yields.     

Basic hydrolysis of glyceryl nitrate esters. II. 1,2-glyceryl and 1, 3-glyceryl dinitrate esters

Kinetics of the basic hydrolysis of 1,2-glyceryl dinitrate (1,2-DNG) and 1,3-glyceryl dinitrate (1,3-DNG) esters were investigated in CO₂-free aqueous calcium hydroxide solutions. The hydrolysis reactions were carried out in a temperature controlled reactor vessel with provision for continuous N₂ sparging of the reaction mixture. Both glyceryl dinitrate esters hydrolyzed via second-order reaction at 25°C. 1,2-DNG in basic solutions isomerized to 1,3-DNG which subsequently hydrolyzed to yield products. The main hydrolysis product of 1,3-DNG was identified as glycidyl nitrate. Other products formed during the basic hydrolysis of DNGs were nitrites and nitrates.     

On-line determination and control of the water content in a continuous conversion reactor using NIR spectroscopy

On-line near infrared spectroscopy was used to determine the water content in a continuous conversion reactor. The NIR predictions were incorporated into the distributed control system (DCS) which then controlled the addition of water to the reactor. The conversion reaction utilizes methanol, water, sodium carbonate and a reactant. Control of the water content is important for a number of reasons. At elevated water levels, a competing hydrolysis reaction increases along with the product solubility in the mother liquor leading to product losses. At reduced water levels, the product becomes anhydrous and the reaction mixture becomes gelatinous, necessitating a shutdown of the reactor for cleaning. The previous procedure for monitoring water was to remove a sample once per hour, transfer the sample to the laboratory, and run a Karl Fisher assay. Upon obtaining results from the lab, an operator would manually adjust the water inlet valve to the reactor. NIR spectroscopy in an on-line mode allows spectra to be collected every 200 s markedly increasing the frequency of results. A partial least squares model was constructed, validated and successfully implemented to predict the water content of the reactor. Further, by feeding the results to the process DCS, water additions to the reactor were fully automated. The increased frequency of sampling by NIR led to an improvement in the control of the water content and decreased the normal amount of equipment downtime. These factors improved process stability and recovery thereby generating an estimated $500,000 in savings over the course of the campaign.     

Photon Equivalents as a Parameter for Scaling Photoredox Reactions in Flow: Translation of Photocatalytic C−N Cross-Coupling from Lab Scale to Multikilogram Scale

With the development of new photocatalytic methods over recent decades, the translation of these chemical reactions to industrial-production scales using continuous-flow reactors has become a topic of increasing interest. In this context, we describe our studies toward elucidating an empirically derived parameter for scaling photocatalytic reactions in flow. By evaluating the performance of a photocatalytic C−N cross-coupling reaction across multiple reactor sizes and geometries, it was demonstrated that expressing product yield as a function of the absorbed photon equivalents provides a predictive, empirical scaling parameter. Through the use of this scaling factor and characterization of the photonic flux within each reactor, the cross-coupling was scaled successfully from the milligram scale in batch to a multi-kilogram reaction in flow.     

水饱和离子液体中萘普生的酶法拆分

 考察了五种水饱和离子液体反应介质中固定化脂肪酶催化外消旋萘普生甲酯的水解. 结果表明,这些具有不同阴阳离子组合的咪唑基离子液体作为反应介质都能促进水解反应的有效进行,但在水饱和1-正丁基-3-甲基咪唑六氟磷酸盐(［bmim］PF6)中,反应进行得更快,转化率更高. 这些离子液体对脂肪酶均有一定的溶解作用并使溶解的脂肪酶失活. 脂肪酶在离子液体中的溶解度与其剩余活性之间有一定的相关性. 为了解决脂肪酶在离子液体中的溶解问题,使用非极性、高比表面积的无定形多孔硅胶YWG-C6H5对脂肪酶进行了固定化. 在水饱和［bmim］PF6中使用固定化脂肪酶催化反应,反应72 h的转化率为28.3%, 产物的对映体过量值为98.2%, 继续进行反应,转化率将增加,但产物的对映体过量值明显下降. 利用离子液体有别于传统有机溶剂的特性,对离子液体的循环使用、产物的回收和水的补充方法进行了研究. 在反复批式反应中,固定化脂肪酶连续使用五次,活性仅略微下降.     

膜反应器中萘普生甲酯的动态拆分

在碱催化连续原位消旋条件下,利用CRL脂肪酶（Candida rugosa lipase）催化的萘普生甲酯立体选择性水解反应。动态拆分制备（S）－普生。使用硫水硅橡胶膜隔离生物催化拆分反应和碱催化消旋反应,解决了常规动态拆分反应中生物催化剂难以承受原位化学消旋苛刻反应条件的难题。为了利于从水－有机溶剂乳化体系中分离产物和克服产物抑制,将亲水半透膜引入搅拌罐反应器,在该膜反应器中进行动态拆分反应。当转化率超过60％时,产物（S）－萘普生的对映体过量值（eep)仍在96％以上,在反应过程中还发现CRL脂肪酶同工酶的转化。     

Lewis Acid–Base Interaction‐Controlled ortho‐Selective C−H Borylation of Aryl Sulfides

An iridium/bipyridine‐catalyzed ortho ‐selective C−H borylation of aryl sulfides was developed. High ortho ‐selectivity was achieved by a Lewis acid–base interaction between a boryl group of the ligand and a sulfur atom of the substrate. This is the first example of a catalytic and regioselective C−H transformation controlled by a Lewis acid–base interaction between a ligand and a substrate. The C−H borylation reaction could be conducted on a gram scale, and with a bioactive molecule as a substrate, demonstrating its applicability to late‐stage regioselective C−H borylation. A bioactive molecule was synthesized from an ortho ‐borylated product by converting the boryl and methylthio groups of the product.     

Selection of the most effective kinetic model of lactase hydrolysis by immobilized Aspergillus niger and free β-galactosidase

The kinetic model of the hydrolysis of lactose by β-galactosidase from Aspergillus niger immobilized on a commercial ceramic monoliths was estimated in the attendance of lactose and its hydrolysis reaction products galactose and glucose. The aim of this work was to developing kinetic model of lactase hydrolysis by Aspergillus niger. The variables in this study are temperature, pH, enzyme concentration, substrate concentration and final product. The optimum temperature used to achieve the best hydrolysis performance in the kinetic model selection was 55 and 60 °C. The optimum pH used for enzyme activity was about 3.5 to 4. Five kinetic models were proposed to confirm experimental data the enzymatic reaction of the lactose hydrolysis by the β-galactosidase. The kinetics of lactose hydrolysis by both Immobilized and soluble lactases were scrutinized in a batch reactor system in the lack of any mass conduction restriction. In both instance the galactose inhibition kinetic models predicted the experimental data. The model is capable to fit the experimental data correctly in the extensive experimental span studied.     

Effect of Internal Diffusional Restrictions on the Hydrolysis of Penicillin G: Reactor Performance and Specific Productivity of 6-APA with Immobilized Penicillin Acylase

A mathematical model that describes the heterogeneous reaction–diffusion process involved in penicillin G hydrolysis in a batch reactor with immobilized penicillin G acylase is presented. The reaction system includes the bulk liquid phase containing the dissolved substrate (and products) and the solid biocatalyst phase represented by glyoxyl-agarose spherical porous particles carrying the enzyme. The equations consider reaction and diffusion components that are presented in dimensionless form. This is a complex reaction system in which both products of reaction and the substrate itself are inhibitors. The simulation of a batch reactor performance with immobilized penicillin G acylase is presented and discussed for the internal diffusional restrictions impact on effectiveness and productivity. Increasing internal diffusional restrictions, through increasing catalyst particle size and enzyme loading, causes impaired catalyst efficiency expressed in a reduction of effectiveness factor and specific productivity. High penicillin G initial concentrations decrease the impact of internal diffusional restrictions by increasing the mass transfer towards porous catalyst until product inhibition becomes significant over approximately 50 mM of initial penicillin G, where a drop in conversion rate and a maximum in specific productivity are then obtained. Results highlight the relevance of considering internal diffusional restrictions, reactor performance, and productivity analysis for proper catalyst and reactor design.     

Quantifying temperature and flow rate effects on the performance of a fixed-bed chromatographic reactor

Chromatographic reactors are based on coupling chemical reactions with chromatographic separation in fixed-beds. Temperature and flow rate are important parameters for the performance of such reactors. Temperature affects mainly adsorption, chemical equilibria, mass transfer and reaction kinetics, whereas flow rate influences residence time and dispersion. In order to evaluate the mentioned effects, the hydrolysis reactions of methyl formate (MF) and methyl acetate (MA) were chosen as case studies. These reactions were performed experimentally in a lab-scale fixed-bed chromatographic reactor packed with a strong acidic ion exchange resin. The chosen reactions can be considered to represent a relative fast (MF) and a relative slow (MA) reaction. The processes which take place inside the reactor were described and simulated using an isothermal equilibrium dispersive model. The essential model parameters were determined experimentally at different temperatures and flow rates. The performance of the chromatographic reactor was evaluated at several discrete constant temperature levels by quantifying product purity, productivity and yield. The work provides insight regarding the influence of temperature and flow rate on values of the model parameters and the performance criteria.     

Chemical Mimics of Aspartate-Directed Proteases: Predictive and Strictly Specific Hydrolysis of a Globular Protein at Asp−X Sequence Promoted by Polyoxometalate Complexes Rationalized by a Combined Experimental and Theoretical Approach

Creating efficient and residue-directed artificial proteases is a challenging task due to the extreme inertness of the peptide bond, combined with the difficulty of achieving specific interactions between the catalysts and the protein side chains. Herein we report strictly site-selective hydrolysis of a multi-subunit globular protein, hemoglobin (Hb) from bovine blood, by a range of Zr^IV-substituted polyoxometalates (Zr-POMs) in mildly acidic and physiological pH solutions. Among 570 peptide bonds in Hb, selective cleavage was observed at only eleven sites, each occurring at Asp−X peptide bonds located in the positive patches on the protein surface. The molecular origins of the observed Asp−X selectivity were rationalized by means of molecular docking, DFT-based binding, and mechanistic studies on model peptides. The proposed mechanism of hydrolysis involves coordination of the amide oxygen to Zr^IV followed by a direct nucleophilic attack of the side chain carboxylate group on the C-terminal amide carbon atom with formation of a cyclic anhydride, which is further hydrolyzed to give the reaction products. The activation energy for the cleavage of the structurally related Glu−X sequence compared to Asp−X was calculated to be higher by 1.4 kcal mol⁻¹, which corresponds to a difference of about one order of magnitude in the rates of hydrolysis. The higher activation energy is attributed to the higher strain present in the six-membered ring of glutaric anhydride (Glu−X), as compared to the five-membered ring of the succinic anhydride (Asp−X) intermediate. Similarly, the cleavage at X−Asp and X−Glu bonds are predicted to be kinetically less likely as the corresponding activation energies were 6 kcal mol⁻¹ higher_, explaining the experimentally observed selectivity. The synergy between the negatively charged polyoxometalate cluster, which binds at positive patches on protein surfaces, and selective activation of Asp−X peptide bonds located in these regions by Zr^IV ions, results in a novel class of artificial proteases with aspartate-directed reactivity, which is very rare among naturally occurring proteases.     

Elucidating the Mechanism and Chemoselectivity in the PBu3-Catalyzed Rauhut-Currier Reaction of Chalcone with Ethyl Acrylate

Disclosing the chemoselectivity and regioselectivity of phosphine-catalyzed Rauhut-Currier (R−C) reaction remains a challenge. Here, a comprehensive study on the possible mechanisms and origins of the chemoselectivity and regioselectivity of PBu₃-catalyzed R−C reactions between ethyl acrylate and chalcone is performed by DFT. Both cross and homo R−C reactions are investigated and compared. The computational results show that the cross R−C reaction is energetically favorable than the homo R−C reaction, with head-to-tail product being generated preferentially. Moreover, the C−C bond formation process is identified to be the regioselectivity- and chemoselectivity-determining step. The CDFT and Parr function analyses are successfully used to predict the origins of chemoselectivity and regioselectivity, respectively. This work would provide a valuable case for exploring the origins of the chemoselectivity and regioselectivity of the phosphine catalyzed reactions, which should be helpful to understand and control the selectivities by rational design.     

Colorimetric method for the quantitative determination of the antibilharzial drug praziquantel and its application to pharmaceutical preparations.

A method for the colorimetric assay of praziquantel has been developed. For the colorimetric assay, it was necessary to hydrolyse praziquantel with 3 mol dm-3 NaOH, 6 mol dm-3 HCl and 85% phosphoric acid separately. 4-Chloro-7-nitro-2,1,3-benzoxadiazole (NBD-Cl) reacts with the basic hydrolysis product in methanolic aqueous phosphate buffer (pH 7.4), resulting in the formation of an orange product with a characteristic absorption maximum at 478 nm. The red-orange product of the interaction between the hydrochloric acid hydrolysis product and NBD-Cl showed an absorption maximum at 486 nm. The colours obtained were stable for 24 h. The colour system obeyed Beer's law in the concentration range 2-15 and 2-18 micrograms ml-1 for the basic hydrolysis product and the acid hydrolysis product, respectively. The results obtained showed good recoveries with relative standard deviations of 0.378 and 0.47% for the basic and the acid hydrolysis product, respectively. The determination limit was found to be 0.124 and 0.150 micrograms ml-1 for the praziquantel basic hydrolysis product and the acid hydrolysis product, respectively. The coloured reaction products obtained with the proposed method were synthesized. The structures of these products were studied and the compounds identified.     

Smart bilayer polymer reactor with cascade/non-cascade switching catalyst characteristics

In this work, a new method is proposed to meet the challenge of preparing new catalysts with cascade/non-cascade switching catalytic property. Inspired from “soft” characteristics and divisional isolation function in natural biological systems, this objective was accomplished by developing a new class of hydrogels made of two unique functional layers with different temperature responses where each may self-govern coupled processes at a specific temperature. This hydrogel polymer reactor exhibited almost no catalytic activity at low-temperature range (<37 °C) as both channels of bilayer hydrogel polymer catalyst were closed. At modest temperatures (between 37 °C and 50 °C), the first step of the tandem reaction (the hydrolysis of p-nitrophenyl acetate (NPA)) showed significant reactivity that arises from the relaxing of the weak polymer complexes in the hydrogel layer. This enabled NPA the access to the acidic catalytic active center of the hydrogel. At range of higher temperatures (>50 °C), the hydrogel catalytic polymer reactor further exhibited significant efficiency towards the hydrolysis reaction of NPA as well as the reduction of the intermediate product p-nitrophenol (NP). This mainly resulted from the opening of both the weak polymer complexes and the stronger polymer complexes hydrogel layers, allowing entrance to both the acidic catalytic active center and the metal nanoparticles active center. As a result, the novel hydrogel polymer reactor could be used to control cascade/non-cascade catalysis reactions. This new protocol enables efficient control of switchable tandem reactions, inspiring for difficulty to control tandem catalytic reactors.     

Reactions of Thorium Oxide Clusters with Water: The Effects of Oxygen Content

Thorium oxide has many important applications in industry. In this article, theoretical calculations have been carried out to explore the hydrolysis reactions of the ThO_n (n=1–3) clusters. The reaction mechanisms of the O-deficient ThO and the O-rich ThO₃ are compared with the stoichiometric ThO₂. The theoretical results show good agreement with the prior experiments. It is shown that the hydrolysis mainly occurred on the singlet potential surface. The overall reactions consist of two hydrolysis steps which are all favourable in energy. The effects of oxygen content on the hydrolysis are elucidated. Interestingly, among them, the peroxo group O₂²⁻ in ThO₃ is converted to the HOO− ligand, behaving like the terminal O²⁻ in the hydrolysis which is transformed into the HO− groups. In addition, natural bond orbital (NBO) analyses were employed to further understand the bonding of the pertinent species and to interpret the differences in hydrolysis.     

Kinetic analysis for hydrothermal depolymerization of nylon 6

We investigated the influences of reaction temperature, time and water density. We also investigated the reaction rate and reaction scheme which is necessary to industrialize this process from the result of hydrolysis of nylon 6 in sub- and supercritical water. The reactions were carried out at temperatures between 573 and 673 K under the estimated pressures of up to 35 MPa (water amount charged in a reactor 0.83-3.79 g/5 cm³ - reactor) for reaction times of 5-60 min. The main products of hydrolysis of nylon 6 by sub- and supercritical water are ?-caprolactam and ?-aminocaproic acid. Based on our experimental results, the reaction scheme of nylon 6 decomposition is represented. Nylon 6 was decomposed into ?-aminocaproic acid by hydrolysis followed by cyclodehydration to ?-caprolactam or decomposition further to lower molecules. At each reaction conditions, the k₁ and k₂ values were determined and the activation energy was calculated.     

Miniaturization of solid-phase reactors for on-line post-column derivatization in narrow-bore liquid chromatography

Summary The use of solid-phase reactors for post-column derivatization in narrow-bore HPLC (1.0mm i.d. analytical columns) is evaluated. Two systems are described, viz. for the determination of N-methylcarbamate pesticides and for that of urea and ammonia. The solid-phase reactor is packed with a strong anion exchange resin and urease immobilized on silica, respectively, to effect the catalytic hydrolysis of the solutes eluting from the analytical column. In both systems, the hydrolysis product is reacted with o-phthalaldehyde followed by fluorescence monitoring. Analytical data are presented and band broadening from various parts of the reaction detector system is discussed. An on-line trace enrichment procedure via a micro precolumn is descried for the trace level determination of N-methylcaramates in surface water samples.     

Esterification reaction kinetics of acetic acid and n-pentanol catalyzed by sulfated zirconia

This study reports experimental data and kinetic modeling of acetic acid esterification with n-pentanol using sulfated zirconia as a catalyst. Reactions were carried out in an isothermal well-mixed batch reactor at different temperatures (50-80°C), n-pentanol to acid molar ratios (1:1-3:1), and catalyst loadings (5-10 wt% in relation to the total amount of acetic acid). The reaction mechanism regarding the heterogeneous catalysis was evaluated considering pseudo-homogeneous, Eley–Rideal, and Langmuir–Hinshelwood model approaches. The reaction mixture was considered a nonideal solution and the UNIQUAC thermodynamic model was used to take into account the nonidealities in the liquid phase. The results obtained indicated that increases in the temperature and catalyst loading increased the product formation, while changes in the n-pentanol to acetic acid molar ratio showed no significant effect. The estimated enthalpy of the reaction was −8.49 kJ mol⁻¹, suggesting a slightly exothermic reaction. The Eley–Rideal model, with acetic acid adsorbed on the catalyst as the limiting step, was found to be the most significant reaction mechanism.     

Continuous attrition bioreactor with enzyme recycling for the bioconversion of cellulose

A new type of reactor, the attrition bioreactor, has been developed to increase the rate of the enzymatic hydrolysis of cellulose and also to cut pretreatment costs. It was found that the attrition bioreactor could be operated continuously or semicontinuously in conjunction with a membrane filter to produce a high cellulose conversion rate and low enzyme consumption. The membrane filter served to contain the enzyme and cellulose within the reactor while allowing sugar to permeate as a product.