反应类等键反应方法及类反应热动力学参数计算

本文提出了反应类等键反应方法,将通常用于热力学性质计算的等键反应方法推广用于类反应中反应势垒和反应焓变的计算. 对碳氢燃料低温燃烧反应机理中的一类重要反应类：?烷基自由基过氧化氢裂解生成烯烃和HO2自由基的反应势垒和反应焓变进行了计算. 通过对该类16个反应中的5个代表反应分别在不同计算水平HF、DFT、MP2、CCSD(T)的比较计算发现,采用等键反应方法可在较低从头算级别计算得到类反应较高精度的反应势垒,提高了计算的效率和精度. 本文采用反应类等键反应方法在B3LYP/6-311G(d,p)计算水平对该类16个反应进行了反应势垒和反应焓变的计算,并建立了反应势垒和反应能的线性自由能关系：delta V=71.02+0.41?delta E.     

异丁烯直接胺化合成叔丁胺反应的热力学研究

叔丁胺是一种重要的有机化工中间体,广泛应用于制备橡胶促进剂,医药,农药,着色剂等诸多下游产物.目前,叔丁胺主要的生产方法,如叔丁脲水解法,异丁烯-氢氰酸法(Ritter法),卤代烃胺化法等存在产品收率较低,涉及强酸/强碱的使用,对设备腐蚀和环境污染严重等问题.异丁烯直接胺化生产叔丁胺,原子利用率100%,是典型的绿色化学反应.20世纪末,BASF公司以β沸石为催化剂,率先实现了异丁烯胺化技术的工业应用.但是,其反应条件苛刻,压力达28 MPa,生产过程能耗大,对设备材质要求高.目前,关于异丁烯直接胺化的文献较少,且相关研究多在远离工业应用的常压条件下进行.同时,对于异丁烯直接胺化反应过程的热力学,特别是缓和反应条件下的热力学尚待进一步系统和深入地研究分析,以期指导低温低压条件下高性能胺化催化剂的研发和工艺条件优化.我们计算了473?573 K间,异丁烯胺化制备叔丁胺反应的ΔrH,ΔrG,Kp等热力学数据.在此基础上,分析了反应温度,压力和氨烯比(摩尔比)对异丁烯平衡转化率(叔丁胺选择性>99%,未予考虑)的影响.结果表明,异丁烯胺化是中等强度的放热反应,升高反应温度会急剧降低异丁烯的平衡转化率,如在5 MPa,氨烯比1的条件下,反应温度从473 K提高到573 K,异丁烯平衡转化率从40.6%降到6.9%.但从动力学角度而言,升温可提高胺化反应速率,因此在特定的反应条件下和催化剂上,必然存在最佳反应温度.提高反应压力和氨烯比有利于提高异丁烯的热力学平衡转化率.开发在低温和相对较低的压力下具有较高胺化活性的催化剂是提高该过程经济性和实用性的关键.在较缓和的反应条件下(523 K,5 MPa,氨烯比4及异丁烯空速0.5 h?1),考察了ZSM-5(R=50和R=412,R为硅铝比,下同),ZSM-11(R=48),MOR(R=10),SAPO-11(摩尔组成,1.6Al2O3:1.0SiO2:1.4P2O5)等不同拓扑结构分子筛以及氧化铝在异丁烯胺化反应中的性能.结果表明,空白试验中,无叔丁胺产物生成.在ZSM-11上的获得最高的异丁烯胺化转化率,为14.2%(达到平衡转化率的52.2%),在ZSM-5(R=50),ZSM-5(R=412)和MOR上,异丁烯转化率分别为13.9%,6.4%和2.9%,叔丁胺选择性均大于99.8%.而SAPO-11和氧化铝未呈现出胺化反应活性.关联氨气程序升温脱附,吡啶吸附红外表征结果及分子筛孔结构特点,表明分子筛胺化活性与其孔径及Br?nsted酸的酸量和酸强度密切相关.为了进一步验证实际反应体系中反应条件对异丁烯胺化反应过程的影响规律,我们在ZSM-11催化剂上,系统考察了反应温度,压力,氨烯比和异丁烯空速对催化剂胺化反应性能的影响及变化规律.结果表明,在其他条件不变的情况下,异丁烯转化率随着温度的升高呈现出先增大后减小的趋势.适当提高原料中氨烯比和反应压力,以及采用较低异丁烯空速有利于促进异丁烯的转化.上述规律与热力学计算结果呈现出较好的一致性.在ZSM-11催化剂上,异丁烯直接胺化反应的较佳反应条件为523 K,5 MPa,氨烯比4,异丁烯空速0.5 h?1.上述结果可为异丁烯直接胺化合成叔丁胺过程新型高效催化剂的研发和反应工艺条件优化提供参考和指导.     

Implicit versus explicit solvent in free energy calculations of enzyme catalysis: Methyl transfer catalyzed by catechol O-methyltransferase

We compare free energy calculations for the methyl transfer reaction catalyzed by catechol O-methyltransferase using the quantum mechanical/molecular mechanical free energy method with implicit and explicit solvents. An analogous methylation reaction in a solution is also studied. For the explicit solvent model, we use the three-point transferable intermolecular potential model, and for the implicit model, we use the generalized Born molecular volume model as implemented in CHARMM. We find that activation and reaction free energies calculated with the two models are very similar, despite some structural differences that exist. A significant change in the polarization of the environment occurs as the reaction proceeds. This is more pronounced for the reaction in a solution than for the enzymatic reaction. For the enzymatic reaction, most of the changes take place in the protein rather than in the solvent, and, hence, the benefit of having an instantaneous relaxation of the solvent degrees of freedom is less pronounced for the enzymatic reaction than for the reaction in a solution. This is a likely reason why energies of the enzyme reaction are less sensitive to the choice of atomic radii than are energies of the reaction in a solution.     

Domino carbopalladation-cross-coupling for the synthesis of 3,3-disubstituted oxindoles

This study examines a domino carbopalladation-cross-coupling reaction for the formation of valuable oxindole scaffolds. Furthermore, the reaction sequence forges vicinal stereocenters in a stereospecific manner through the formation of two carbon-carbon bonds and, thereby, rapidly generates complexity. The reaction gives high yields for a variety of acrylamide substrates, and various organoboranes have also been evaluated for the cross-coupling. This work offers insight into the relative rates determining a successful carbopalladation-cross-coupling reaction and how to favor the desired reaction pathway.     

Theoretical study on the alkaline hydrolysis of methyl thioacetate in aqueous solution

A base-catalyzed hydrolysis reaction of thiolester has been studied in both gas and solution phases using two ab initio quantum mechanics calculations such as Gaussian09 and CPMD. The free-energy surface along the reaction path is also constructed using a configuration sampling technique, namely, the metadynamics method. While there are two different reaction paths obtained for the potential profile of the base-catalyzed hydrolysis reaction for thiolester in the gas phase, a triple-well reaction path is computed for the reaction in the solution phase by two quantum mechanics calculations. Unlike the S(N)2 mechanism (a concerted mechanism) found for the gas-phase reaction, a nucleophilic attack from the hydroxide ion on the carbonyl carbon to yield a tetrahedral intermediate (a stepwise mechanism) is observed for the solution-phase reaction. Moreover, the energy profiles computed by these two theoretical calculations are found to be very comparable with those determined experimentally.     

A computational study of the heats of reaction of substituted monoethanolamine with CO2

Various amines have been considered as materials for chemical capture of CO(2) through liquid-phase reactions to form either carbamate or carbamic acid products. One of the main challenges in these CO(2)-amine reactions lies in tuning the heat of reaction to achieve the correct balance between the extent of reaction and the energy cost for regeneration. In this work, we use a computational approach to study the effect of substitution on the heats of reaction of monoethanolamine (MEA). We use ab initio methods at the MP2/aug-cc-pVDZ level, coupled with geometries generated from B3LYP/6-311++G(d,p) density functional theory along with the conductor-like polarizable continuum model to compute the heats of reaction. We consider two possible reaction products: carbamate, having a 2:1 amine:CO(2) reaction stoichiometry, and carbamic acid, having a 1:1 stoichiometry. We have considered CH(3), NH(2), OH, OCH(3), and F substitution groups at both the α- and β-carbon positions of MEA. We have experimentally measured heats of reaction for MEA and both α- and β-CH(3)-substituted MEA to test the predictions of our model. We find quantitative agreement between the predictions and experiments. We have also computed the relative basicities of the substituted amines and found that the heats of reaction for both carbamate and carbamic acid products are linearly correlated with the computed relative basicities. Weaker basicities result in less exothermic heats of reaction. Heats of reaction for carbamates are much more sensitive to changes in basicity than those for carbamic acids. This leads to a crossover in the heat of reaction so that carbamic acid formation becomes thermodynamically favored over carbamate formation for the weakest basicities. This provides a method for tuning the reaction stoichiometry from 2:1 to 1:1.     

Correlation of relative rates of PdCl(2) oxidation of functionalized acyclic alkenes versus alkene ionization potentials, HOMOs, and LUMOs.

Investigations of the title reaction, carried out by plotting logs of the relative reaction rates vs IPs, vs HOMOs, and vs LUMOs, reveal multiple nearly parallel lines of correlation with small negative slopes in each. Overall, the natural grouping into monosubstituted and disubstituted alkenes gives better correlations than that obtained by using all alkenes. Comparison with analogous plots for other reactions indicates that the mechanism for this reaction has similarities to that for hydroboration, the major difference being that the lines in the plots for hydroboration have positive slopes, indicating an electrophilic rate-determining step involving the pi electrons, while those for the title reaction have small negative slopes, indicating a nucleophilic rate-determining step. Of the two reaction mechanisms proposed for the title reaction, only one has a nucleophilic attack at the complexed alkene as the rate-determining step, and therefore, this work supports that reaction mechanism.     

A new way of probing reaction networks: analyzing multidimensional parameter space

Technically relevant partial oxidation reactions represent complex reaction networks. Establishing a kinetic model for a system of multiple consecutive and parallel reaction steps is a challenging goal. The synthesis of acrylic acid by oxidation of propane using MoVTeNb mixed oxide as catalyst is such a reaction network. In an on-going study, a 10- fold parallel reactor set-up is used to vary systematically reaction conditions in a broad range over a single, well-defined MoVTeNb oxide. Selectivity and product yield in a multidimensional parameter space can give insight into the reaction network. Apparent activation energies and reaction orders of propane are derived for several conditions. Optimum reaction conditions within the investigated parameter space are specified. The results presented within this contribution contain about 200 data points measured in steady states each corresponding to reaction conditions that differ in temperature, contact time, and propane feed concentration. The fact that this data was collected in less than two months shows clearly the advantage of parallel screening of reaction conditions for mechanistic studies.     

低热固相反应的反应机理研究(Ⅰ)——冷融熔机理和冷溶熔机理的模型

本文提出了低热固相反应的冷融熔机理和冷溶熔机理,其中冷融熔机理主要针对于不含结晶水的反应体系,冷溶熔机理主要针对于含结晶水的反应体系,并对低热固相反应动力学提出冷融熔/冷溶熔、扩散、反应、成核、生长的五步机理。两种机理都避开了分子在固相晶格中的扩散,从而对低热固相反应的扩散问题进行了有效的解释,并给出了低热固相反应的热力学和动力学判据。     

Synthesis of 2,3-anti-3,4-anti and 2,3-anti-3,4-syn propionate motifs: a diastereoselective tandem sequence of Mukaiyama and free-radical-based hydrogen transfer reactions

[reaction: see text] Reported herein is a strategy employing a Mukaiyama reaction in tandem with a hydrogen transfer reaction for the elaboration of 2,3-anti-3,4-anti and 2,3-anti-3,4-syn propionate motifs. The mode of complexation is controlled through monodentate or chelate pathways for the Mukaiyama reaction to give access to either syn or anti aldol products, precursors of the free-radical reduction reaction. Boron Lewis acid is used to control the free-radical reaction through the exocyclic pathway.     

液态聚乙二醇作为绿色反应介质在有机反应中的应用

低分子量的液态聚乙二醇（PEG）作为一种新型的绿色有机反应溶剂正受到人们的极大关注。PEG具有好的热稳定性、不挥发、不易燃、无毒、生物可降解、廉价易得,以及易于回收和循环使用。此外,PEG可以溶解众多的有机化合物和有机金属配合物。因此,PEG作为有机溶剂的替代品和作为均相催化剂的载体已经成功地应用到许多有机反应中,它们包括还原反应、氢化反应、氧化反应、不对称双羟基化反应、Heck反应、Suzuki交叉偶联反应、Michael加成反应、不对称Aldol反应、Baylis-Hillman反应、脂肪酶催化的反应和聚合反应等。本文对这一领域的研究进展作一综述。     

Ab initio quantum mechanical/molecular mechanical molecular dynamics simulation of enzyme catalysis: the case of histone lysine methyltransferase SET7/9

To elucidate enzyme catalysis through computer simulation, a prerequisite is to reliably compute free energy barriers for both enzyme and solution reactions. By employing on-the-fly Born-Oppenheimer molecular dynamics simulations with the ab initio quantum mechanical/molecular mechanical approach and the umbrella sampling method, we have determined free energy profiles for the methyl-transfer reaction catalyzed by the histone lysine methyltransferase SET7/9 and its corresponding uncatalyzed reaction in aqueous solution, respectively. Our calculated activation free energy barrier for the enzyme catalyzed reaction is 22.5 kcal/mol, which agrees very well with the experimental value of 20.9 kcal/mol. The difference in potential of mean force between a corresponding prereaction state and the transition state for the solution reaction is computed to be 30.9 kcal/mol. Thus, our simulations indicate that the enzyme SET7/9 plays an essential catalytic role in significantly lowering the barrier for the methyl-transfer reaction step. For the reaction in solution, it is found that the hydrogen bond network near the reaction center undergoes a significant change, and there is a strong shift in electrostatic field from the prereaction state to the transition state, whereas for the enzyme reaction, such an effect is much smaller and the enzyme SET7/9 is found to provide a preorganized electrostatic environment to facilitate the methyl-transfer reaction. Meanwhile, we find that the transition state in the enzyme reaction is a little more dissociative than that in solution.     

烷基自由基β位裂解反应类反应势垒与速率常数的精确计算

提出反应类等键方法并用于高温燃烧机理中一类重要反应——烷基自由基β位裂解反应的反应势垒和速率常数的精确校正计算. 通过10种不同从头算水平对类反应中5个代表反应的反应势垒的计算发现, 用反应类等键反应方法和直接从头算方法获得的5 个代表反应的反应势垒最大绝对偏差的平均值分别为5.32 和16.16 kJ·mol^-1, 表明反应类等键反应方法计算的反应势垒对不同水平从头算方法的依赖性小, 可在较低从头算水平计算得到精确的反应势垒, 解决大分子体系反应势垒的精确计算问题. 此外应用反应类等键反应方法在BHandHLYP/cc-pVDZ 从头算水平计算了3 个代表反应的速率常数, 并与文献报道的实验值进行了比较, 其在500-2000 K温度区间内计算速率常数与实验速率常数中较大值与较小值的比值k_max/k_min的平均值为1.67, 最大值也仅有2.49. 表明应用反应类等键反应方法在较低从头算水平即可对同类反应的速率常数进行精确计算.最后在BHandHLYP/cc-pVDZ从头算水平用反应类等键反应方法计算了13个烷基自由基β位裂解反应的速率常数.     

Quantum chemical studies of a model for peptide bond formation. 3. Role of magnesium cation in formation of amide and water from ammonia and glycine

The SN2 reaction between glycine and ammonia molecules with magnesium cation Mg2+ as a catalyst has been studied as a model reaction for Mg(2+)-catalyzed peptide bond formation using the ab initio Hartree-Fock molecular orbital method. As in previous studies of the uncatalyzed and amine-catalyzed reactions between glycine and ammonia, two reaction mechanisms have been examined, i.e., a two-step and a concerted reaction. The stationary points of each reaction including intermediate and transition states have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of each reaction. Substantial decreases in free energies of activation were found for both reaction mechanisms in the Mg(2+)-catalyzed amide bond formation compared with those in the uncatalyzed and amine-catalyzed amide bond formation. The catalytic effect of the Mg2+ cation is to stabilize both the transition states and intermediate, and it is attributed to the neutralization of the developing negative charge on the electrophile and formation of a conformationally flexible nonplanar five-membered chelate ring structure.     

The reaction of porphyrins with organolithium reagents

Porphyrins react readily with organolithium reagents, preferentially in the meso positions. The overall reaction is a nucleophilic substitution and proceeds via initial reaction of the organic nucleophile with a meso carbon yielding an anionic species which is hydrolyzed to a porphodimethene (5,15-dihydroporphyrin), formally constituting an addition reaction to two Cm positions. Subsequent oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) yields meso-substituted porphyrins. The reaction is highly versatile as it is accomplished in high, often quantitative yields with various alkyl or aryl lithium reagents. In addition, LiR can be used for reaction with a variety of metal complexes (best with NiII, but also with ZnII, CuII, and CoII) and most useful with free base porphyrins. Similarly beneficial this reaction can be used in sequence for the introduction of 1, 2, 3, or 4 (different) meso substituents giving for the first time an entry into any desired meso-substituted porphyrin. If meso-substituted porphyrins are used, reaction with LiR can be used for either the preparation of phlorins (already known reaction), porphodimethenes (5,15-dihydroporphyrins, including those with exocyclic double bonds, for example, 5(1),5(2)-didehydroporphyrins) or chlorins (2,3-dihydroporphyrins) depending on the substituent type in the reactant porphyrins. Thus, this reaction presents a generally applicable method for the facile and versatile functionalization of porphyrins.     

Effect of stoichiometry and diffusion on an epoxy/amine reaction mechanism

The bulk phase kinetics of an epoxy (DGEBA) /amine (DDS) thermoset have been studied using DSC, FTIR, and ¹³C-NMR. In the absence of catalyst, the reaction was found to involve a main exothermic reaction between epoxide and amine hydrogen and a side reaction between tertiary amine formed in the main reaction and epoxide. The main reaction was exothermic while the side reaction had no discernable exotherm. Etherification did not occur to any significant extent. Since only the main reaction is exothermic, DSC was very useful for studying the main reaction kinetics. FTIR was used for determining whether epoxide and amine hydrogen were consumed at different rates as a way of following the side reaction. An IR band previously unused by other investigators was used to monitor the amine hydrogen concentration. NMR confirmed the above mechanism by identifying the formation of a quaternary ammonium ion/alkoxide ion pair as a reaction product of tertiary amine and epoxide. This mechanism has been successfully fit to a rate law valid over the entire extent of reaction. The rate constant for the epoxy/amine addition reaction was found to depend on hydroxide concentration (extent), reaction temperature, and glass transition temperature and included contributions from uncatalyzed and autocatalyzed parts. The side reaction (quaternary ammonium ion formation) formed weak bonds which did not affect the overall system T_g. Both reactions were second order. The rate constants for the main reaction first increase with increasing extent due to autocatalysis by hydroxide before decreasing due to the diffusion limit caused by gelation and vitrification. © 1995 John Wiley & Sons, Inc.     

Theoretical studies of metallo (Li and Na)-ene reaction mechanisms

The reaction mechanisms of allyl-lithium and allyl-sodium with ethylene were studied by ab initio molecular orbital (MO) methods. The reaction mechanisms were analyzed by a CiLC-IRC method on the basis of ab initio CASSCF MOs. The ene reaction pathways of allyl-Li and allyl-Na with ethylene were located. The complex between allyl-metal and ethylene for both systems is found in the first step of the reaction, and then the metal migration and new C-C bond formation occur synchronously through the transition state. The complexation energies are -13.2 and -9.6 kcal/mol for Li and Na systems, respectively. The activation energy barriers from the reactants are 3.5 kcal/mol for the Li system and 2.0 kcal/mol for the Na system at the MRMP2 calculation level. These barriers are significantly lower than that of the ene reaction of propene with ethylene as the parent reaction. The CiLC-IRC analysis shows that the reaction of allyl-metal with ethylene is a concerted ene reaction mechanism, not a metal catalysis and/or a stepwise reaction.     

Kinetochromic spectrophotometry-I Determination of fluoride by catalysis of the zirconium-xylenol orange reaction

The reaction between slightly aged solutions of zirconyl chloride and Xylenol Orange is catalysed by the presence of substoi-chiometric amounts of fluoride, phosphate, arsenate, sulphate, citrate or oxalate. The reaction provides a method for determining fluoride in amounts from 0.5 to 5 mug in a final volume of 100 ml. This kineto-chromic reaction provides an effective molar absorptivity of 2.0 x 10(5) for the fluoride ion. The colour reaches maximal development within 90 min and remains stable thereafter for 60 min, when measured against a reaction system blank containing no fluoride. Because of its substoichiometric nature the reaction may not be used for the determination of large amounts of fluoride.     

Total synthesis of leustroducsin B

Leustroducsin B was synthesized via a convergent route based on division of the leustroducsin molecule into three segments A, B, and C. Two coupling reactions (Julia coupling reaction and Nozaki-Hiyama-Kishi (NHK) reaction) were employed for coupling of segments A and B: segment A1 for the Julia coupling reaction was prepared by a combination of Sharpless asymmetric epoxidation and an epoxide-cleavage reaction with an organoaluminum reagent, while segment A2 for the NHK reaction was synthesized from optically active alcohol that had previously been prepared by lipase-catalyzed kinetic resolution. Segment B, whose structure was modified with some functional groups, was synthesized from (R)-malic acid by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation, and segment C, containing a cyclohexane moiety, was prepared by asymmetric Diels-Alder reaction. Segment B was first coupled with segment A1 via the Julia coupling reaction, but the yield was low due to unexpected epimerization. The NHK reaction of segment A2 proceeded to give the coupling product in good yield. This product was coupled with segment C via Wittig and Stille coupling reactions, and finally, phosphorylation was carried out by partial hydrolysis of a cyclic phosphate to give leustroducsin B.     

Development of an efficient and safe process for a grignard reaction via reaction caloremetry

A Grignard reaction of reactantA and phenyl magnesium chloride is used to make a pharmaceutical intermediate at the production scale. The elimination of protecting groups onA was proposed as a means to reduce synthesis costs. This new synthesis route, however, had process efficiency and safety issues associated with it: (1) build-up of unreactedA in the reactor, (2) influence ofA's particle size on the reaction rate, (3) the sensitivity of the reaction rate to the reaction temperature and to the (changing) solvent composition, and (4) the highly exothermic nature of the reaction.The Mettler RC1 Reaction Calorimeter was used to quantify the influence of solvent composition, temperature, and particle size on the reaction rate. Results indicated a dramatic effect of solvent composition and reaction temperature on the reaction rate; for example, over a temperature range of just 30°C, the reaction time decreased from more than a day to just a few minutes. At such high reaction rates, the vessel jacket could not remove the reaction heat sufficiently and the internal temperature rose adiabatically.These results were used to make process design and operation recommendations for safe and efficient plant operation with this modified Grignard reaction system.The authors would like to thank the following for their assistance in this work: E. Daugs for preparing the Grignard reagents, K.L. Gonzales for her help in running the experiments and in the subsequent data work-up; P.M. Russell for his assistance in the design of the slurry addition assembly, and K. Chritz and J. Engel for performing the HPLC analyses of the samples.