A change from stepwise to concerted mechanism in the acid-catalysed benzidine rearrangement: a theoretical study

The monoprotonated mechanism of the benzidine acid-catalysed rearrangement of hydrazobenzene (corresponding to a second order kinetics) is studied and compared with the diprotonated mechanism (corresponding to a third order reaction and previously studied). The nature of the two mechanisms is found to be completely different: a concerted closed-shell sigmatropic shift in the monoprotonated, a stepwise radical cation recoupling in the diprotonated. The activation energies, combined with the energetics of the protonation equilibria, are also very different: 35 kcal mol^?1 for the former and 26 kcal mol^?1 for the latter (in good agreement with the experimental data). These values make the third order diprotonated mechanism favoured with respect to the second order monoprotonated mechanism for the rearrangement of hydrazobenzene, as found at typical experimental acid concentrations.     

Synthesis of 3-methoxyazetidines via an aziridine to azetidine rearrangement and theoretical rationalization of the reaction mechanism

The synthetic utility of N-alkylidene-(2,3-dibromo-2-methylpropyl)amines and N-(2,3-dibromo-2-methylpropylidene)benzylamines was demonstrated by the unexpected synthesis of 3-methoxy-3-methylazetidines upon treatment with sodium borohydride in methanol under reflux through a rare aziridine to azetidine rearrangement. These findings stand in contrast to the known reactivity of the closely related N-alkylidene-(2,3-dibromopropyl)amines, which are easily converted into 2-(bromomethyl)aziridines under the same reaction conditions. A thorough insight into the reaction mechanism was provided by both experimental study and theoretical rationalization.     

Acid-catalyzed nucleophilic aromatic substitution: experimental and theoretical exploration of a multistep mechanism

The mechanism for the acid-mediated substitution of a phenolic hydroxyl group with a sulfur nucleophile has been investigated by a combination of experimental and theoretical methods. We conclude that the mechanism is distinctively different in nonpolar solvents (i.e., toluene) compared with polar solvents. The cationic mechanism, proposed for the reaction in polar solvents, is not feasible and the reaction instead proceeds through a multistep mechanism in which the acid (pTsOH) mediates the proton shuffling. From DFT calculations, we found a rate-determining transition state with protonation of the hydroxyl group to generate free water and a tight ion pair between a cationic protonated naphthalene species and a tosylate anion. Kinetic experiments support this mechanism and show that, at moderate concentrations, the reaction is first order with respect to 2-naphthol, n-propanethiol, and p-toluenesulfonic acid (pTsOH). Experimentally determined activation parameters are similar to the calculated values (Delta H exp not equal =105+/-9, Delta H calcd not equal =118 kJ mol(-1); Delta G exp not equal =112+/-18, Delta G calcd not equal =142 kJ mol(-1)).     

A theoretical study of the mechanism and stereoselectivity of the Diels-Alder cycloaddition between difluoro-2-methylencyclopropane and furan

A theoretical study of the molecular mechanism and stereoselectivity of the Diels-Alder cycloaddition reaction between difluoro-2-methylencyclopropane and furan has been carried out at the B3LYP/6-31G+^∗∗ level of theory. The calculation of activation and reaction energies indicates that the 3-endo cycloadduct is favored both kinetically and thermodynamically, which is in agreement with the experimental data. Analysis of the bond order and charge transfer in the transition states shows that this reaction takes place via a synchronous-concerted mechanism.     

Experimental and theoretical studies of Diels-Alder dimerization of 1,2,3,4,5-pentachlorocyclopentadiene and of Diels-Alder cycloaddition of polychlorinated cyclopentadienes to norbornadiene

Diels-Alder cyclodimerization of 1,2,3,4,5-pentachlorocyclopentadiene (1) affords 2a as the exclusive reaction product. Diels-Alder cycloaddition of 1 to norbornadiene also proceeds stereoselectively to produce a single [4+2] cycloadduct, 4c. The structures of 2a and 4c were established unequivocally via application of single crystal X-ray crystallographic techniques. The origins of the observed diastereofacial selectivity in each of these cycloaddition processes have been investigated by application of semiempirical (AM1 Hamiltonian) and ab initio (Hartree-Fock 3-21G*) calculations. The computational results thereby obtained, which are based upon consideration of the kinetically favored transition state for each of the two cycloaddition reactions studied, are consistent with experiment. These semiempirical and ab initio methods also have been used to investigate the mechanisms of the Diels-Alder reactions that have been used to prepare aldrin and isodrin (7 and 8, respectively). The results thereby obtained suggest that isodrin formation via Diels-Alder cycloaddition of cyclopentadiene to 1,2,3,4,7,7-hexachloronorbornadiene proceeds with kinetic control of product stereochemistry.     

Structural assignment of Diels-Alder adducts: an experimental and theoretical approach

A detailed NMR analysis with total assignment of (1)H and (13)C NMR data for the endo and the exo adducts, obtained by Diels-Alder reaction between 2-cyclohexenone and cyclopentadiene, is described. The unequivocal assignment of the endo and exo structures was performed by (1)H and (13)C NMR. These assignments were supported by theoretical chemical shift calculations at GIAO/HF level using 6-311 + g(2d, p) from optimized structures at the B3LYP/6-31g(d) level.     

Quantum mechanical inspection of the Diels-Alder approach to biaryls mechanism

The Diels-Alder reaction of substituted cyclohexadienes with substituted phenylacetylenes offers an attractive alternative for the synthesis of biaryl compounds via a two-step cycloaddition/cycloelimination pathway. Quantum mechanical calculations using B3LYP and M06-2X density functional methods for the reaction of 2-chloro-6-nitrophenylacetylene with 1-carbomethoxy-cyclohexadiene show the reaction proceeds by a stepwise diradical [4+2] cycloaddition followed by concerted [2+4] cycloelimination of ethylene. [2+2] cycloadducts are also the result of stepwise addition. [2+2] cycloadducts isomerize to [4+2] cycloadducts via diradical pathways, which involve the same diradical intermediate in cycloaddition. There is also a competitive conrotatory ring opening followed by trans-cis double bond isomerization pathway of the [4.2.0] bicycle (the [2+2] cycloadduct) to give the cis,cis,cis-1,3,5-cyclooctatriene.     

The surface charge density/surface potential relationship and the Poisson-Boltzmann equation

A procedure is described which provides an approximate analytic expression for the relationship between the surface charge density and the surface potential of a spherical or cylindrical colloidal particle in a general type of electrolyte. The first approximation is found and the approximation error is given. Also derived are the fourth approximation for a symmetric z-z type electrolyte and the second approximation for a symmetric z-z, 2z-2z type electrolyte.     

The surface potential of a spherical colloid particle: functional theoretical approach

By using the iterative method in functional analysis, the potential of the electrical double layer of a spherical colloid particle, which is represented by the so-called Poisson-Boltzmann (PB) equation, has been solved analytically under general potential conditions. With the help of the diagram method in mathematics, the surface potential of the particle has been defined from the second iterative solution. The influence of the parameters included in the solutions on the surface potential has been studied. The results show that the surface potential of the particle increases as the temperature of the system, the aggregation number, and the concentration of ions increase, but decreases with an increase in the dielectric constant and the valence of the ions. The corresponding space charge density also has been illustrated in this work.     

Base-induced rearrangement of tritylamines to imines: discovery and investigation of the mechanism

An unexpected compound, the aniline derived benzophenone imine, was isolated when tritylamine was treated with n-BuLi and alkyl halides, during the formation of N-alkyl tritylamines, in the process of preparing primary amines. A nucleophilic attack of the nitrogen anion of tritylamide on the adjacent C-bonded phenyl, either substituted or not, involving a bridging anionic intermediate, is proposed for this base-induced tritylamine rearrangement to produce the corresponding imine. Electron-withdrawing groups in the aromatic ring, favoring the negative charge development, affect the relative migratory tendencies.     

Retro Diels-Alder reaction under mild conditions: experimental and theoretical studies

We describe experimental as well as theoretical results to support the role of cyclopropane in a retro Diels-Alder reaction at lower temperature.     

Experimental and theoretical study of the 2-alkoxyethylidene rearrangement

The rearrangement of 2-ethoxyethylidene, generated photochemically from a nonnitrogenous precursor, leads to ethyl vinyl ether. Although this product could result, in principle, from a 1,2-hydrogen shift and/or a 1,2-ethoxy shift in the carbene, a deuterium labeling study indicates an essentially exclusive preference for hydrogen migration. The experimental results are in agreement with CCSD and W1BD calculations for the simpler 2-methoxyethylidene system that show a prohibitively large barrier for the methoxy shift and a negligible barrier for the hydride shift.     

A concise synthesis of Tamiflu: third generation route via the Diels-Alder reaction and the Curtius rearrangement

Our third generation synthesis of Tamiflu was achieved in 12 steps from commercially available starting materials, using the Diels-Alder reaction and Curtius rearrangement as key steps.     

A DFT exploration of the enantioselective rearrangement of cyclohexene oxide to cyclohexenol

In this paper, we present computational results for the (1S,3R,4R)-3-(pyrrolidinyl)-methyl-2-azabicyclo[2.2.1]heptane mediated rearrangement of cyclohexene oxide. The results nicely explain the differences in enantioselectivities between catalytic and stoichiometric mode between different ligands, and provides a rational for the identification of non-stereospecific background reactions as the major cause of decreased enantioselectivity in catalytic reactions for sterically hindered diamines.     

Hybrid supermolecule-polarizable continuum approach to solvation: Application to the mechanism of the Stevens rearrangement

Semiempirical molecular orbital theory has been used to study the effects of solvation by acetonitrile on the Stevens rearrangement of methylammonium formylmethylide to 2-aminopropanal. Three methods of solvation have been used to investigate both the electrostatic and specific solvent–solute effects of solvation: a supermolecule calculation involving the complete geometry optimization of up to six solvent molecules about the solute, the conductor-like screening model (COSMO) polarizable continuum method which allows for geometry optimization of the solute in a solvent defined by its dielectric constant, and a hybrid method in which up to five solvent molecules are incorporated inside the solute cavity and complete geometry optimization of the complex is carried out within the polarizable continuum. A comparison of the calculated geometries, rearrangement activation energies, and enthalpies of solvation from these approaches is presented, and the explicit versus bulk solvation effects are discussed. The overall effect of all methods for incorporating solvation effects is that the radical pair pathway is perferred over the concerted mechanism. © 1996 by John Wiley & Sons, Inc.     

Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement as an equivalent of the inverse electron demand hetero Diels-Alder reaction

A highly stereoselective formal inverse electron demand hetero Diels-Alder reaction (HDA) occurs on reaction of 2-aryl-alpha,beta-unsaturated aldehydes with cyclopentadiene. The major pathway for this transformation is shown to be a Lewis acid-catalyzed tandem Diels-Alder reaction/retro-Claisen rearrangement.     

Electron transfer activation of the Diels-Alder reaction: Quantitative relationship to charge transfer excited states

The Diels-Alder cycloaddition of anthracene to tetracyanoethylene (TCNE) is quantitatively compared to alkylmetal insertion under the same reaction conditions. In both systems, the observation of transient charge transfer (CT) absorption bands is related to the presence of 1:1 electron donor-acceptor complexes of anthracene (Ar) and alkylmetal (RM) donors with the TCNE acceptor. The activation free energies ΔG3 for anthracene cycloaddition and alkylmetal insertion are found to be equal to the energies of ion-pair formation, i.e. [Ar⁺TCNE^?] and RM⁺TCNE^?], which are evaluated from the CT transition energies hν_CT. Indeed, the differences in the rates of alkylmetal insertion and anthracene cycloaddition by a factor of more than 10⁹, are shown quantitatively to arise from the differences in ion-pair solvation ΔG^s. The same differences in ΔG^s also apply quantitatively to the free ions, [Ar⁺] and [RM⁺], independently derived from the electrochemical and iron(III) oxidations of alkylmetals and aromatic compounds, respectively, by outer- sphere electron transfer. The charge transfer formulation of the activation process but provides a unifying basis for comparing such diverse processes as Diels-Alder cycloadditions and organometal cleavages, when a common electron-deficient acceptor is employed. The relationship to the concerted mechanisms of the Diels-Alder reaction is discussed.