Analysis of regioselectivity of free radical addition to olefins by the Morokuma scheme

The regioselectivity of free radical attack on olefins is considered with respect to the correspondence between energy components in the Morokuma scheme and their analogs in the orbital scheme (FMO approximation) in terms of ambivalence of radicals and the effectiveness of reactant deformation, with the purpose of fitting a CT model.Institute of Organic Chemistry, Academy of Sciences of the Ukrainian SSR Kiev. Translated from Teoreticheskaya i Éxperimental Khimiya, Vol. 27, No. 4, pp. 474–478, July–August, 1991. Original article submitted March 14, 1991.     

Halobenzenes and Ir(I): kinetic C-H oxidative addition and thermodynamic C-Hal oxidative addition

A (PNP)Ir fragment undergoes facile, room-temperature oxidative addition of C-H bonds in arenes and haloarenes in preference to aromatic carbon-halogen bonds. This preference, however, is determined to be kinetic in nature. Oxidative addition of C-Cl and C-Br is preferred thermodynamically. The products of the C-Cl or C-Br oxidative addition are separated from the C-H oxidative addition products by a high activation barrier and are only accessible at >100 degrees C. Of the C-H oxidative addition products of chlorobenzene, the isomer with the o-ClC6H4 ligand has the lowest energy.     

Regioselective sulfonation of 2-porphyrinylthiophene under kinetic and thermodynamic control

Sulfonation of meso-tetra(thien-2′-yl)porphyrin with concentrated sulfuric acid was found to produce several tetrasulfonated meso-tetra(thien-2′-yl)porphyrin isomers, where sulfonic acid groups were substituted at the 5- or the 4-positions of the thienyl groups, and the tetrasodium salts of the isomers were successfully isolated by reversed-phase HPLC. Temperature dependence of the production ratio of the isomers revealed that sulfonation reactions at the 5- and the 4-positions of 2-porphyrinylthiophene occur under kinetic and thermodynamic control, respectively.     

Ab initio study of the thermodynamic and kinetic stability of the ammonium radical

An increasing interest in the possible existence of the NH₄ radical has emerged in recent years. In this paper we report an ab initio UHF CI study of the ammonium radical, an investigation of parts of the energy surface around NH₄ and a theoretical prediction of the kinetic parameters of the radical formation and dissociation reactions within the framework of the TST theory. The ground state of the ammonium radical appears to be of the Rydberg type. Its ionization potential is found to be 4.29 eV. The NH₄ formation reaction from NH₂ + H₂ is very slightly exothermic whereas the reaction from NH₃ + H is slightly endothermic. We find a transition state of C_3v symmetry for the dissociation of NH₄ into NH₃ + H. The insertion of H₂ into NH₂ occurs according to a two-step mechanism whose determining step corresponds to the crossing of a saddle point with C_s symmetry previously obtained in the study of the reaction NH₂ + H₂ → NH₃ + H. Finally, we predict for NH₄ and ND₄ lifetimes of 0.1 and 1.4 μs respectively.     

Conformational study of the intramolecular diels-alder reaction of a pentadienyl acrylate. Theoretical evaluation of kinetic and thermodynamic control

Acrylate 4, prepared from diacetylrhamnal, underwent intramolecular Diels-Alder cycloaddition to give the thermodynamically disfavored trans-fused gamma-lactone 15 as the major product, along with two stereoisomeric cycloadducts. A computational analysis of each of the four transition states arising from 4 and the corresponding cycloadducts permits an understanding of the contrasting requirements for kinetic versus thermodynamic control of the reaction.     

Kinetic and thermodynamic stability of acenes: Theoretical study of nucleophilic and electrophilic addition

To understand the reactivity of acenes, particularly pentacene, the addition of HCl and water to acenes was studied for the benzene-nonacene series at the B3LYP/6-31G(d) level of theory. Surprisingly, the reactivity of the acenes increases along the series up to hexacene and remains constant from hexacene and above due to the biradical character of the ground state of higher acenes. While the exothermicity of HCl and water additions are very similar, the activation barriers for HCl and water additions differ by a constant factor of ca. 27 kcal/mol. The barrier for the addition of HCl varies from 44 kcal/mol for benzene to 16-18 kcal/mol for pentacene-nonacene, whereas the barrier for the addition of water varies from 71 kcal/mol for benzene to 43-46 kcal/mol for pentacene-nonacene. The transition states (TSs) for the addition of water to acenes are relatively "late" on the reaction coordinate, compared to the "earlier" TSs for the addition of HCl. There is a substantial substituent effect on the energy barriers for these reactions. HCl behaves as an electrophile, with rhoHCl (vs rho p) = -4.48 and -3.39 for anthracenes and pentacenes, respectively, while water behaves as a nucleophile, with rhoHCl (vs rho p) = 2.35 and 1.39 for anthracenes and pentacenes, respectively.     

Theoretical study of the addition and abstraction reactions of hydroxyl radical with uracil

The addition as well as abstraction reactions of hydroxyl radical (OH) with the nucleic acid base, uracil (U), in the gas phase has been explored at the B3LYP/6-31+G(d,p) level of density functional theory (DFT). The energy barrier of the OH addition to both the C5 and C6 positions of the uracil is less than 1 kcal/mol while the hydrogen abstractions (H-abstractions) from either the N1 or the N3 positions are ∼9.5 kcal/mol. Further the energetics of these reactions are assessed by applying the effect of aqueous medium through the polarizable continuum model (PCM). Both the gas and the solution phase data established that the thermodynamic and kinetic factors are more favorable for the OH addition to either C5 or C6 positions of the uracil than the H-abstraction reactions. Moreover, calculations at the MPW1K/6-31+G(d,p), CCSD(T)/6-31+G(d,p)//B3LYP/6-31+G(d,p) and CCSD(T)/6-31+G(d,p)//MPW1K/6-31+G(d,p) levels of theoretical methods qualitatively supported the B3LYP/6-31+G(d,p) results.     

The regioselectivity of addition to carbon nanotube segments

Calculations (AM1) demonstrate that Clar's valence bond model predicts the long-range reactivity patterns of hydrogenation of carbon nanotube (CNT) segments. CNT segments behave as other polycyclic aromatic hydrocarbons--hydrogenation of double bonds is energetically preferred over hydrogenation of aromatic sextets. The frontier molecular orbitals of CNT segments have greatest amplitude at the double bonds, suggesting that Clar's model also predicts kinetic reactivity.     

Theoretical study of mechanism and kinetics for the addition of hydroxyl radical to phenol

The reaction mechanism and kinetics for the addition of hydroxyl radical(OH) to phenol have been investigated using the hybrid density functional(B3LYP) method with the 6-311++G(2dp,2df) basis set and the complete basis set(CBS) method using APNO basis sets,respectively.The equilibrium geometries,energies,and thermodynamics properties of all the stationary points along the addition reaction pathway are calculated.The rate constants and the branching ratios of each channel are evaluated using classical transition state theory(TST) in the temperature range of 210 to 360 K,to simulate temperatures in all parts of the troposphere.The ortho addition pathway is dominant and accounts for 99.8% 96.7% of the overall adduct products from 210 to 360 K.The calculated rate constants are in good agreement with existing experimental values.The addition reaction is irreversible.     

Ab initio mechanistic study of radical reactions: The regioselectivity of the addition of atomic hydrogen to fluoroacetylene and 1,1-difluoroethylene

Ab initio molecular orbital calculations of the transition states and barrier heights for the addition of atomic hydrogen to fluoroactylene and 1,1-difluoroethylene are presented. The relative reactivity of these compounds and the regioselectivity of the addition reactions are analyzed in terms of chemically interpretable contributions by means of the energy decomposition scheme proposed by Morokuma. The usual PMO approach of the problem is discussed in this context. A rationalization of some of the experimental rules of radical reactivity is given.     

Structure elucidation of the intermediate in triethylborane-mediated radical addition of oxime ethers with 2D- and 3D-DOSY NMR

The structures of the components in the triethylborane-mediated radical addition reaction of oxime ether were investigated by 1H- and 3D-DOSY NMR methods. It has been impossible to physically separate the unstable intermediates; therefore, the structures were thus far unidentified. It has been possible to elucidate the structures of these unstable intermediates using Diffusion-Ordered Spectroscopy (DOSY) methods for the reaction in an NMR tube. The DOSY methods resolved the spectra of each starting compound, intermediate and product having different diffusion coefficients. The structure of the intermediate was shown to be due to the bonding of diethylborane to the nitrogen atom of the alkoxyamino group.     

QM study on regioselectivity in the synthesis of pyrimido[4,5-b][1,4]benzothiazines: kinetic and thermodynamic point of view

In the present study, the experimentally observed regioselectivity in pyrimido[4,5-b][1,4]benzothiazine synthesis has been modeled using density functional theory method at M06/6-311++G** level. Also the tautomerism of all four tautomers of 6-ethyl-2-thio(1H) pyrimidin-(3H)-4-one as an important intermediate through the reaction path in pyrimido[4,5-b][1,4]benzothiazine synthesis has been investigated extensively in the gas and solution phase. The stability order of tautomers was found as A > D > B > C, in gas and chloroform solvent; however, changing to more polar solvents this order was changed as A > B > D > C using polarized continuum model. In the next step, we focused on another significant feature of this synthesis which has major role in the observed regioselectivity. Two proposed reaction paths with two different transition states that it seems the mode of its intermolecular cyclization has a special role in regioselectivity of the final product have been considered. Comparison of our calculated NMR and IR spectrum with those already reported for some pyrimido[4,5-b][1,4]benzothiazines demonstrates a reliable agreement. Moreover, all obtained results in the gas and solution phase confirm that the synthesis of above-mentioned compound is thermodynamically more favorable than the possible regioisomeric product.     

Balancing kinetic and thermodynamic control: the mechanism of carbocation cyclization by squalene cyclase

Molecular dynamics simulations with a combined quantum mechanical and molecular mechanical (QM/MM) potential have been carried out to investigate the squalene-to-hopene carbocation cyclization mechanism in squalene-hopene cyclase (SHC). The present study is based on free energy simulations by constructing the free energy surface for the cyclization steps along the reaction pathway. The picture that emerges for the carbocation cyclization cascade is a delicate balance of thermodynamic and kinetic control that ultimately favors the formation of the final hopanoids carbon skeleton. A key finding is that the five- to six-membered ring expansion process is not a viable reaction pathway for either C- or D-ring formation in the cyclization reaction. The only significant intermediate is the A/B-bicyclic cyclohexyl cation (III), from which two asynchronous concerted reaction pathways lead to, respectively, the 6,6,6,5-tetracyclic carbon skeleton and the 6,6,6,6,5-pentacyclic hopanoids. Experimentally, these two products are observed to have 1% and 99% yields, respectively, in the wild-type enzyme. We conclude that the product distribution in the wild-type enzyme is dictated by kinetic control of these two reaction pathways.     

Theoretical study of the regioselectivity of the Huisgen reaction

From the structure of a series of spiro (pyrrolidine-2,3′-oxindole) derivatives synthesized by Huisgen reaction of isatin, α-amino acids, and different olefins, different regioselectivities were found. The possible mechanism of the Huisgen reaction of oxindole azomethine ylide and the substituent of olefins was investigated using a B3LYP/6-311G* level of theory, and the results show that the regioselection depends on the energy barrier between the stacking state and the regioisomer. This mechanism can also be applied to the illumination of other Huisgen reactions.     

Simultaneous determination of kinetic and thermodynamic parameters from fast-reaction kinetic measurements

A combined stopped-flow temperature-jump apparatus interfaced with a dedicated microcomputer has been used to study the complexation reaction of iron(III) with thiocyanate in aqueous solution. Kinetic rate-constants (k(f) = 143 l.mole(-1) .sec(-1) from T-jump, k(f) = 150 l.mole(-1) .sec(-1) from stopped flow), equilibrium constants (K = 143 from T-jump, K = 150 from stopped flow) and the thermodynamic enthalpy change (DeltaH(c) = -6.7 kJ/mole) could be independently determined from the simultaneous application of the two techniques.     

DFt study of the regioselectivity of addition of sulfenylchloride to ethenes

The electrophilic addition reactions of methylsulfenyl chloride to the double bonds of functionalized ethenes have been studied theoretically. Density functional theory (DFT) calculations have been applied for starting species and ethene‐based sulfonium intermediates bearing substitutes at α‐carbon atom to study geometrical parameters and electronic states of plausible intermediate forms. The quantum chemical optimizations of intermediates indicate that the episulfonium ion is the most likely methyl‐ or carboxyl‐substituted ethane‐based intermediate. However, with phenyl substituents the intermediate is more like a carbonium than an episulfonium ion. The role of sulfur appears to be that of directing the stereochemistry of the addition reaction of chloride, forming the trans product upon nucleophilic attack on the C—C bond of the episulfonium ion. The regioselectivity features of the opening of the episulfonium ion by the chloride anion depend on the LUMO and LUMO+1 of the episulfonium ion and the approaching HOMO of chlorine. The results of the theoretical investigations are in agreement with experiment. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:695–703, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20378     

Controlling fullerene addition sequences, regioselectivity and magic numbers via metal encapsulation

A systematic density functional study of chlorine addition to C(70) up to C(70)Cl(12) confirms experimental observations of regioselectivity and stability of C(70)Cl(10). We show that K@C(70) follows an alternative addition sequence with different isomers and magic numbers to C(70) such as KC(70)Cl(3). This prediction is important for controlling functionalisation behaviour via encapsulation and endofullerene purification.