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.     

A new insight into Fischer-Tropsch synthesis

Fischer-Tropsch (FT) reaction is an important synthetic route to convert CO and H(2) to fuels and chemicals in industry. To date, its reaction mechanism remains uncertain. With extensive density functional theory studies on FT reactions on Ru, we compare quantitatively several C/C coupling mechanisms that are likely to be involved. We found that a well-regarded CH(2) + CH(2)R (R = H or alkyl) mechanism possesses high reaction barriers, and a stepwise C + CR mechanism has been identified that may be relevant to FT synthesis.     

Explorations into new reaction chemistry

This Review describes the basic concepts that have guided our exploration of new chemical reactions by giving examples of results from my research group. Our strategy of carrying out research is to investigate three to four different topics at a time so we can gather as many results as possible. These may at first appear unrelated to each other but may have the potential to be united into a greater hypothesis after repeated feedback. Three scenarios from our research are presented: the "oxidative-reductive condensation reaction" devised in 1960, which after an interval of nearly 40 years brought forth the new concept of using compounds of structure Ph(2)POR as reducing reagents; the "TiCl(4)-aldol reaction" of 1973 that eventually led to the present "base-promoted aldol reaction" through a chain of ideas; and the "glycosylation reaction using fluorosugars" from 1984 which recently bloomed into "stereocontrolled glycosylation". Thus, it can be said that by reviewing what we had done before, we were able to expand on it to achieve new outcomes.     

A new tin-free source of amidyl radicals

[reaction: see text] The readily available N-(O-ethyl thiocarbonylsulfanyl)amides are powerful amidyl radical precursors that undergo 5-exo cyclization to give pyrrolidinone derivatives via a radical-chain reaction initiated by a small amount of lauroyl peroxide.     

A new solvent-dependent mechanism for a triazolinedione ene reaction

The ene reaction between 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) and tetramethylethylene has been investigated using QM/MM calculations in water, methanol, DMSO, and acetonitrile. The effects of solvation on the mechanism and rates of reaction are elucidated using two-dimensional potentials of mean force (PMF) simulations utilizing free-energy perturbation theory and Monte Carlo statistical mechanics. A new mechanism is proposed where direct formation of an open dipolar intermediate following the addition of PTAD to the alkene is rate-limiting and the pathway toward ene product is significantly dependent on the reaction medium. In protic solvents, the open dipolar intermediate may proceed directly to the ene product or reversibly form an aziridinium imide (AI) intermediate that does not participate in the reaction. However, in aprotic solvents the open intermediate is short-lived (<10-11 s) and the ene product forms via the AI intermediate. The calculated free energies of activation are in close agreement with those derived from experiment, e.g., DeltaG of 14.9 kcal/mol compared to 15.0 kcal/mol in acetonitrile. Density functional theory calculations at the (U)B3LYP/6-311++G(2d,p) level using the CPCM continuum solvent model were also carried out and confirmed a zwitterionic, and not diradical, open intermediate present in the reaction. Only the QM/MM methodology was able to accurately reproduce the experimental rates and differentiate between the protic and aprotic solvents. Solute-solvent interaction energies, radial distribution functions, and charges are analyzed and show that the major factor dictating the changes in reaction path is hydrogen bond stabilization of the charge separations spanning 2 to 4 atoms in the intermediates and transition states.     

A new approach for isothermal calorimetric technique

Using flexible heat flux sensors mounted on the lateral and bottom of outside reactor wall, a new approach is developed for isothermal calorimetric technique to overcome the disadvantages of heat flow calorimetric methods. Although the proposed system needs a calibration procedure before or after the reaction completion to evaluate the lateral heat transfer area, the measurement is versatile and totally independent of the reaction media, jacket fluid, and the variations of heat transfer coefficient. Knowledge of the variations of the heat transfer coefficient is essential for the effective control and scale up of a reactor and can be inferred by the new method during the reaction. The stirrer power and the heat loss can be determined easily as well. No pre-calibration is needed for the sensors and no heating element is applied inside the reactor for temperature control. Experiments are carried out to validate the performance of the new proposed technique. With the help of a heater, the heat generated in the reactor is measured at various levels of power input. The predicted heater power inputs are in good agreement with the corresponding heat inputs. The relative detection limit in the range of 0.8–1 W L⁻¹ is expected for this technique. Using the hydrolysis of acetic anhydride, the heat of reaction at 25°C is determined, which is within the range reported in the literatures. The capability of the system to deal with the variations in the overall heat transfer coefficient is also demonstrated using a simulated reaction.     

Organocatalytic kinetic resolution cascade reactions: new mechanistic and stereochemical manifold in diphenyl prolinol silyl ether catalysis

A new cascade reaction involving an iminium-catalyzed intramolecular oxa-Michael addition followed by an enamine-catalyzed intermolecular Michael addition is reported herein. This cascade reaction generates enantiopure, highly functionalized tetrahydropyrans and tetrahydrofurans in a one-pot reaction and in up to 89?% combined yield and up to 99?% ee. This cascade reaction is catalyzed by diaryl prolinol silyl ethers, which are a privileged class of catalysts. The stereochemical outcome of these cascade reactions is unprecedented. Computational studies indicate that this stereochemical outcome arises from nonclassical hydrogen-bonding interactions between the electrophile and the substrate, and from entropic considerations of preorganization. The unprecedented configurations of the cascade products, combined with the computational models, reveal for the first time that asymmetric induction by diaryl prolinol silyl ether catalysts is not always exclusively reagent controlled. The stereochemical outcome also arises from a kinetic resolution or dynamic kinetic resolution of the β-stereocenter through an enamine-catalyzed intermolecular reaction. This unprecedented organocascade reaction mechanism may be adaptable to diaryl prolinol silyl ether-catalyzed cascade reactions, in which both the iminium- and enamine-catalyzed steps are intermolecular, an underdeveloped type of cascade reaction.     

一个新的用于反应散射计算的L^2平动基函数集合

本文通过构造新的L^2平动基函数集合改进了Shima-Baer方法.新集合中不再含有任何人工可调参数,取而代之的是反应体系的分子特性常数.由于在平动基函数中含有在非经典区域内的高度衰减因子,从而大大提高了反应几率对平动基函数展开的收敛速度.对共线交换反应H+H~2→H~2+H的计算结果表果,对平均基函数展开的收敛速度已接近包含畸变势的计算结果.改进后的Shima-Baer方法计算量明显降低.     

Structure and reactivity of radical ions: new twists on old concepts

Electron transfer is the simplest reaction possible, yet it has a profound impact on the structure and reactivity of organic compounds. These changes allow a new look at some of the fundamental concepts that are used to explain organic chemistry, such as symmetry, aromaticity, and bonding. The results from high-level electronic structure calculations are used to analyze the mechanistic differences in the pericyclic reactions of simple hydrocarbons and their radical cation counterparts. The importance of state symmetry correlation, Jahn-Teller distortions, delocalization, and fractional bonding for the reaction pathways of hydrocarbon radical cations is discussed.     

F+OH reactive collisions on new excited 3A" and 3A' potential-energy surfaces

Global three-dimensional adiabatic potential-energy surfaces for the excited 2(3)A" and 1(3)A' triplet states of OHF are obtained to study the F(2P)+OH(2pi)-->O(3P)+HF(1sigma+) reaction. Highly accurate ab initio calculations are obtained for the two excited electronic states and fitted to analytical functions with small deviations. The reaction dynamics is studied using a wave-packet treatment within a centrifugal sudden approach, which is justified by the linear transition state of the two electronic states studied. The reaction efficiency presents a marked preference for perpendicular orientation of the initial relative velocity vector and the angular momentum of the OH reagent, consistent in the body-fixed frame used with an initial collinear geometry which facilitates the access to the transition state. It is also found that the reaction cross section presents a rather high threshold so that, in an adiabatic picture, the two excited triplet states do not contribute to the rate constant at room temperature. Thus, only the lowest triplet state leads to reaction under these conditions and the simulated rate constants are too low as compared with the experimental ones. Such disagreement is likely to be due to nonadiabatic transitions occurring at the conical intersections near the transition state for this reaction.     

Phenoxyhydroxypropylhydroxyethylcellulose—new amphiphilic cellulose derivative

A new amphiphilic cellulose derivative phenoxyhydroxypropylhydroxyethylcellulose of substitution degree up to 0.67 was synthesized by reaction of water-soluble hydroxyethylcellulose with 2,3-epoxypropylphenylether in the presence of sodium hydroxide as a catalyst. The chemical composition of the derivative was confirmed by means of UV, IR- and ¹³C-NMR-spectroscopy. The derivatives with substitution degree up to 0.12 are soluble in water and water–alcohol mixtures. With increasing substitution degree, the polymers lose their water solubility, but still dissolve in water–alcohol mixtures. All products are soluble in aprotic solvents. The effect of the reaction conditions, such as temperature and molar ratios of reaction components, on both the reaction rate and degree of substitution was investigated.     

A new mechanism for gas phase ozone–olefin reactions

A new mechanism for gas phase ozone-olefin reactions is proposed. The mechanism involves biradical intermediates which can react in a variety of ways. One of the possible reaction modes corresponds to the Criegie mechanism originally proposed to explain solution ozonolysis reactions and generally also accepted in the past for gas phase reactions. However, an examination of the gas phase data on ozone–olefin reactions and of the thermochemical and kinetic requirements for these reactions indicates that the Criegie reaction mode may be the least important of various other reaction possibilities. Those other reaction possibilities involve intramolecular H abstractions and rearrangements in biradical intermediates. The proposed mechanism provides very reasonable explanations for a number of unusual observations on gas phase ozonolysis. These are the formation of peroxidic bound products, aldehyde and 1,2-dicarbonyl product fluorescences, and unexpected carbonyl product formations.     

The first example of a diastereoselective thio-Ugi reaction: a new synthetic approach to chiral imidazole derivatives

The first example of a diastereoselective thio-Ugi reaction with chiral alpha-methylbenzylamine is described. The reaction results in formation of two diastereomers of thioamides, the major of which was isolated. We have found that under similar conditions stereochemical results of the thio-Ugi reaction are opposite to stereochemical results of the Ugi reaction. Several chiral thioamides were synthesized. The reaction of thioamides with ammonia results in substituted amidines, which can be cyclized to imidazole derivatives in aqueous HCl. The synthesis of chiral imidazole derivatives was elaborated. Using certain approaches, both isomers of a key synthon in the synthesis of SB203386 (an orally bioactive HIV-1 protease inhibitor) were prepared. The scope, limitations, and stereochemistry of the approach are discussed.     

A new interpretation of the Baylis-Hillman mechanism

[reaction: see text] On the basis of reaction rate data, we have proposed a new mechanism for the Baylis-Hillman reaction involving the formation of a hemiacetal intermediate. We have determined that the rate-determining step is second order in aldehyde and first order in DABCO and acrylate. We have shown that this mechanism is general to aryl aldehydes under polar, nonpolar, and protic conditions using both rate data and two isotope effect experiments.     

A new practical one-pot conversion of phenols to anilines

A novel one-pot synthesis of anilines from phenols was developed. Using this methodology, anilines are produced in good yield (86%) by a reaction of phenols with 2-bromo-2-methylpropionamide and NaOH in DMA via Smiles rearrangement. Phenols, which are substituted electron-withdrawing groups, are more reactive for Smiles rearrangement. Thiophenols are also converted to anilines. The process is a convenient, safe, and inexpensive method for large-scale preparation of anilines. [reaction: see text]     

Reaction mechanism of uracil bromination by HBrO: a new way to generate the enol-keto form of 5-bromouracil

Knowledge on the uracil bromination reaction is helpful for understanding the origin of the mutagenicity of 5-bromouracil (BrU). To get more details about this reaction, we explore the corresponding reaction mechanism by theoretical method. A total of seven pathways were studied for this purpose. The diketo form of BrU is observed as the main product in these pathways, which agrees well with experimental results. The most energy-favorable reaction pathway is found to be that Br and OH attacked the opposite sides of uracil. The reaction intermediate reported in the experiment is predicted to be reasonably stable. In the following step, a dehydration process occurs between H11 and O13-H14 when there are no explicit H(2)O taking part. However, when there are explicit water molecules in the environment, explicit H(2)O will lower the reaction barrier in the formation of reaction intermediates and the final product BrU. A proton-transfer process from C5 to O10 is facilitated by explicit H(2)O, which results in enol-keto form intermediate of this modified base (defined as BrU*). These results indicate a new way to generate the enol-keto form of BrU.     

Synthesis of new binuclear ferrocenyl compounds by hydrosilylation reactions

Ferrocenyl silanes are prepared by treatment of Grignard reagents produced from 4-chlorobutylferrocene derivatives and chlorodimethylsilane in THF. Butenylferrocenes are prepared by the elimination reaction of 4-chlorobutylalkylferrocenes by sodium tert-butoxide in DMSO. A hydrosilylation reaction between a butenyl compound and ferrocenylsilane occurred in dry toluene at room temperature in the presence of the Karstedt catalyst to produce the desired binuclear ferrocenyl compound in good to high yields. The electrochemical behavior of new ferrocenyl compounds were studied by cyclic voltammetry in CH₃CN/0.1 M LiClO₄, and the relation between the peak currents and the square root of the scan rate, showed that the redox process is diffusion-limited.     

P-Heterocyclic carbenes as potential ligands in the design of new metathesis catalysts. A computational study

Density functional calculations are reported concerning the olefin metathesis characteristics of a variety of P-heterocyclic carbene (PHC) complexes. The calculations employ model catalysts of the type (PMe3)(PHC)Cl2Ru=CH2, the PHC ligands being 1,3-dihydro-1,3-diphosphol-2-ylidene PH, 1,3-diphenyl-1,3-diphosphol-2-ylidene PPH, and 1,4-dihydro-1,4-diphosphol-2-azol-5-ylidene PNH. Complexes with N-heterocyclic carbenes (NHC) are included for comparison. Associative and dissociative reaction pathways are considered, the latter ones representing the favored reaction mechanisms. Calculations show that the rate determining step is ring opening of a ruthena-cyclobutane intermediate. In comparison with NHC model catalysts, the PHC compounds have lower phosphine dissociation energies, and also form weaker pi-complexes with an olefinic substrate. Compared to the initially formed pi-complexes, the ruthena-cyclobutane is more stable for PHC- than for NHC-catalysts. The catalytic activity of model PHC-compounds in comparison with NHC-compounds is discussed on the basis of the calculated reaction profiles. In this context, different models for enhanced reactivity of NHC-based catalysts that have been proposed in the literature are considered as well. It is demonstrated that the nature of the substituent of the carbene phosphorus not only exhibits a steric influence on the course of the reaction, but a significant stereoelectronic effect as well. Further, agostic interactions in ruthena-cyclobutane intermediates are investigated.     

A new three-component domino synthesis of 1,4-dihydropyridines

Cerium ammonium nitrate (CAN) catalyzed the three-component domino reaction between aromatic amines, α,β-unsaturated aldehydes, and ethyl acetoacetate, providing an efficient new entry into 1,4-dihydropyridines. This new reaction requires very mild reaction conditions, has water as the only side product and is complementary to the classical Hantzsch synthesis in that it is well suited to the preparation of N-aryl-5,6-unsubstituted dihydropyridines. Experiments in the presence of a radical trap suggest that a one-electron oxidative mechanism can be excluded and that CAN acts as a Lewis acid.     

Some new aspects of the Boyer reaction

[reaction: see text] The reaction outcome of 2-azidoethanol and aliphatic aldehyde is found to be dependent on the catalyst and the structure of the azido alcohol. Under the catalysis of Cu(II) triflate, the corresponding acetal is obtained. A similar reaction between 2-aryl-2-azidoethanol and aldehyde catalyzed by BF3 yields a mixture of 3-oxazoline and 2-oxazoline. The latter reaction has been used for the preparation of 3-oxazolines in good enantioselectivity.