The role of protein relaxation in protein action has been modeled as a bounded diffusion process, involving a single Smoluchowski equation with a sink term. This is insufficient when the ligand within the protein, or the active site, can have multiple states. Examples are the states of the active site of an enzyme, such as cholesterol oxidase (unbound, bound, reduced) or the ligand location within myoglobin. To treat such situations, we consider multi-tier bounded-diffusion models, which involve coupled Smoluchowski equations for harmonic potentials with appropriate sink terms.

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Antimony porphysrin (SbTPP) complexes are able to covalently bind with two axial ligands, thus introducing the functionalized group on the axial-ligand. We have investigated the functionality and material transformation using the functionalized SbTPP complexes. The SbTPP having difluorobornyl-5-dipyrrinylphenyl (Bdpy) group was analyzed under irradiation of Bdpy moiety in term of axial ligand-to-porphyrin energy transfer. The SbTPP having azacrown ether on axial ligand was analyzed from the standpoint of the metal ion-recognition. The silica-gel supported SbTPP was used as visible-light driven photocatalyst for dechlorination from chlorophenols, and photo-epoxidation of cycloalkenes, and bactericidal effect.

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Recently, we have reported the synthesis of the first stable silabenzene, 1-silanaphthalene, 2-silanaphthalene, and 9-silaanthracene utilizing kinetic stabilization afforded by an efficient steric protection group, 2,4,6-tris[bis(trimethylsilyl)methyl]phenyl (denoted as Tbt). Here, the experimental and theoretical studies on structures and reactions of silaaromatics will be described. Although it was found that the silaaromatics have considerable aromaticity by taking account of their structural feature into consideration, these silaaromatics readily undergo 1,2- and/or 1,4-addition reactions with MeOH, acetylene derivatives, nitrile oxides, CCl₄ and so on. Detailed studies on the selectivity of these addition reactions based on the results of experiments and theoretical calculations will be presented. In addition, dimerization reactions and photochemical isomerization reactions of silaaromatics will be described.

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Photoirradiation of organosillicon compounds bearing a 2-(phenylazo)phenyl group as intramolecularly coordination site is expected to cause not only isomerization of the azo groups, but also reversible switching of the coordination states of silicon between a usual tetracoordinate state and a highly reactive pentacoordinate state. We report here the photocontrol of reactivities of a highly coordinate disiloxane and allylsilane without changing other conditions by taking advantage of the coordination state change. (E,E)-Tetrafluorobis[2-(phenylazo)phenyl]disiloxane (E,E)-2 decomposed very slowly in the solution to give trifluorosilane (E)-1. On the other hand, photoirradiation of (E,E)-2 gave a mixture of (Z)-1 and (Z,Z)-2, both of which were converted to (E)-1 fast at room temperature. Photoirradiation accelerated the decomposition of (E,E)-2 to (E)-1. Addition of fluoride ion also accelerated the formation of (E)-1. Formation mechanism of (E)-1 as well as the reaction control of allyldifluorosilane (E)-5 will also be discussed.

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Free radical reactions have recently emerged as a powerful tool in organic synthesis, especially in the synthesis of organofluorine compounds. We have been developing the novel methods for the synthesis of fluorine compounds using radical species. We would like to report here the following two radical reactions as tools for the synthesis of the promising synthetic intermediates for organofluorine compounds. 1) A wide variety of fluoroalkylated products can be prepared using fluoroalkyl radicals which are much more reactive for olefins than alkyl radicals. However, the reactions of perfluoroalky radicals with unsaturated molecules in the presence of oxygen have rarely been employed for organic synthesis, because of the high reactivity of fluoroalkyl radicals with oxygen. We found simultaneous introduction of perfluoroalkyl radical and molecular oxygen into olefin to give perfluoroalkylated alcohol and ketone. 2) Ring-opening reactions of gem-difluorocyclopropyl ketones are known. We investigated the radical reactions of gem-difluorocyclopropyl aldehyde with silyl radical, and found the ring-opening of the aldehyde to give fluorinated silyl enol ether under neutral conditions.

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The ambiphilic character of onium ylides enables the intermolecular C-C bond formations, e.g., Wittig- and Corey-reacton. However, ethereal oxonium ylides have been the exception for long. This is due to their extremely short lifetime that kinetically disfavors the attack by carbon-electrophiles. On this basis, in our present study, the utilization of oxonium ylides for synthetically useful carbon-carbon bond forming reaction was investigated. The ambiphilicity of cyclic oxonium ylides seems to bring about the reaction with carbon electrophiles when appropriate modification is made. Indeed, Rh(2)-catalyzed reaction of diazocarbonyl compounds bearing a cyclic acetal ring, in the presence of Rh-catalyst and titanium compound (Lewis acid), effectively afforded the expected carbon-carbon bonded ring-expansion product(s).

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The oxidative condensation of aldehydes catalyzed by thiazolium salts is of interest in relation to the in vivo reaction from pyruvate to acetyl CoA. In order to have information to understand mechanism of the natural reaction and to apply it to the artificial reaction system, we carried out the mechanistic studies of its model reaction systems. The reaction of p-substituted benzaldehyde with 4,4'-disubstituted azobenzene in the presence of octanethiol, 3-butyl-4-methylthiazolium bromide and triethylamine, which were employed as a nucleophile, catalyst, and base, respectively, in dichloromethane gave the thiol ester together with the hydrazide formed from the corresponding benzoic acid and hydrazobenzene as by-product. And it was found that the product distribution was dependent on both substituents of benzaldehyde and azobenzene. Substituent effects on pseudo-first-order rate constants for the reaction from benzaldehydes in deuterium chloroform were investigated by ¹H-NMR. The Hammett-plot of the observed rate constants against substituent constants (σ) of benzaldehydes was curved, indicating the presence of plural rate-determining steps. Moreover, the study of the substituent effect of azobenzene derivatives endorsed that the rate-determining step was shifted with the electrophilicities of p-substitueted benzaldehydes.

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Mechanism of photoinduced phenyl-rearrangement of phenacyl sulfonates (mesylate, tosylate, triflate) were investigated in TFE and MeCN by the aid of solvent effect, leaving group effect, effect of added trapping reagents and laser flash photolysis. The photosolvolyses of three phenacyl sulfonates in TFE afforded nucleophilic substitution product by solvent. Phenacyl tosylate additionally afforded phenacyl alcohol, which is obtained by the oxidation of phenacyl radical. These result indicates the intervention of phenacyl carbocation and radical in the photosolvolysis. The yields of phenyl rearranged product were increased in the photosolvolysis of phenacyl mesylate and triflate which afforded little amount of radical derived products, as well as in the photosolvolysis of phenacyl chloride that affords little nucleophilic substitution product. The result suggest that the phenyl rearrangement proceed through a intermediate that does not suffer nucleophilic solvent attack. The addition of azide to the photosolvolysis of phenacyl mesylate in TFE resulted in the decrease of nucleophilic substitution product yield, whereas the yield of phenyl-rearranged product was little affected. Addition of nitroxide, on the other hand, decreased the yield of phenyl-rearranged product, and phenacyl-nitroxide adduct was obtained in corresponding yield. These results indicate the photoinduced phenyl-rearrangement proceeds through phenacyl radical intermediate.

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Two reaction mechanisms, inversion and rotation, are possible for intramolecular isomerization at C=N double bonds. Within the inversion mechanistic framework, there are two variants, one with planar TS and the other with perpendicular TS. We have previously demonstrated experimentally that the reaction of (CF₃)₂C=N-Ar proceeds via the inversion mechanism with gradual change from one variant to the other depending on the substituent on Ar. In the present study, MO/DFT and MD computations were carried out to analyze the modes of mechanistic change with substituent for the reactions of (CF₃)₂C=N-Ar and other related systems. It was found that the TS structure changes gradually from the planar to perpendicular geometry when the substituent on Ar becomes more electron withdrawing. Such change in the TS geometry arises from more effective conjugation between the lone pair on N and an electron-withdrawing substituent on Ar. The mechanism of the C=N isomerization will be fully discussed on the basis of the substituent effects on the barrier height and the TS geometry as well as the analyses of the intrinsic reaction coordinate and MD simulations.

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When a prochiral reactant and a reagent element are connected through 2,4-pentanediol (PD), a reaction species generated from the reagent moiety reacts internally with the reactant moiety. Applicable combinations of the two moieties extend in a wide range, and selectivities in their reactions are very high to give essentially optically pure compounds after elimination of the PD tether. Although selectivities with the PD tether are too high to measure their temperature dependency, other lower analogues like a 1,3-butanediol tether resulted in an imperfect stereoselectivity, and it showed almost no temperature dependency. The low temperature dependency of a sufficiently high stereoselectivity means that the selectivity is governed by the entropy term at the transition states. The advantage of this entropy-controlled mechanism is revealed in a flash vacuum pyrolysis (FVP) performed at 250-350° C. The origin of the differential activation entropy was deduced from some intramolecular reaction rates measured for different tethers. By this analysis, it was disclosed that strict stereocontrol with two methyl groups on the PD tether must be attributable to acceleration of one diastereomeric process and deceleration of the other by the entropy term.

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Mechanisms of some organic solid state reactions were studied by monitoring these reactions with IR spectral measurements. Monitoring of a K₂CO₃-assisted Rap-Stoermer reaction of salicylaldehyde (1) and phenacyl bromide (4) showed that, firstly, a 1:1 complex (3) of the potassium salt of 1 (2) and 1 is formed, thereafter 3 is converted into 2. Secondly, the benzoylmethyl ether of 1 (5) produced by a substitution reaction of 2 with 4 gives the cis-dihydro-2-benzoylbenzofuran intermediate (6) which upon dehydration results in the final product, 2-benzoylbenzofuran (7). The intermediates, 2 and 6 were isolated as colorless crystals. The cis-structure of 6 was determined by X-ray analysis. However, structure of 3 was not clarified, since 3 did not form appropriate crystal for X-ray analysis. Benzoylation reaction of 1,2-dihydroxynaphthalene (8) with p-toluoyl chloride (9) was found to proceed via a 2:1 complex (10) of 8 and its dibenzoate (11). The complex 10 was isolated and its crystal structure was determined by X-ray analysis. By monitoring with IR spectral measurements, an imine derivative was detected as an intermediate of Thorpe reaction. As an intermediate of Na₂CO₃-assisted Knoevenagel reaction of 2-formylnaphthalene with malononitrile, an ionic intermediate derived from the reaction product, malononitrile and Na₂CO₃ was detected, although its structure was not elucidated yet.

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In order to evaluate the effect of the alkyl substituent at the nitrogen atom in amino acids and π-π interactions involving phenylalanine, dipeptides bearing N-methylglycine, N-methylalanine, and para-substituted phenylalanine were synthesized. The hydrolysis of 11 kinds of dipeptides catalyzed by carboxypeptidase Y and carboxypeptidase A was studied. There was found a good linear relationship between Michaelis-Menten constant K_m and hydrophobic parameters evaluated by reversed-phase HPLC. Also observed was a good linear relationship between catalytic constant k_cat in the enzymatic hydrolysis of the dipeptides and π-π interactions of monosubstituted benzene evaluated by graphitic carbon-phase HPLC.

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Prostaglandin H synthases (PGHSs) are heme-containing enzymes that catalyze the conversion of arachidonic acid (AA) to prostaglandin H₂ by dioxygenation. This biosynthetic pathway is interesting in that the complex organic molecule can be produced in one step from a simple one. The trigger of this reaction is the H abstraction from AA by a tyrosyl radical. There, however, are no preceding examples of the organic reactions, which utilize an aryloxyl radical as a mediator, because of its instability. Here. we report the mimic of the active sites in PGHS using ferric 'twin-coronet' porphyrin (TCP), which contains four equivalent naphthol moieties in its hydrophobic and chiral cavities on both faces of the porphyrin ring. The mCPBA oxidation of TCP in CH₂Cl₂ at -40°C successfully gave the corresponding oxidized species having a naphthoxyl radical and an iron(IV) porphyrin, which were characterized by UV-vis, ESR, and resonance Raman spectroscopies. The oxygenase reaction of an 1,4-diene by the generated species proceeds through regioselective H radical abstraction at the 3-CH₂ and stereoselectively gives the corresponding cis,trans-dienyl hydroperoxide in a catalytic manner. Thus, the present system is considered to be a good modeling reaction of PGHSs. This reaction is also the first example, which utilizes unstable Ar-O radical being susceptible to oxidation as a mediator in catalytic oxygenation.

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Porphyrin isomers have been received much attention in recent years because of their diverse applications in biology, medicine, catalysis and material science. Particularly, N-confused porphyrin (NCP), is a porphyrin isomer in which one of the pyrrole rings is confused. The confused pyrrole affords the unique properties for this ligand, which are not observed in normal porphyrins. In this lecture, I would like to focus on one of the most important properties of NCP, the NH tautomerism. Previously, we have reported that the NH tautomerism can be controlled by solvent polarity. In non-polar solvents such as dichloromethane, an inner 3H tautomer [P(3H)], having both CH and two NHs inside the porphyrin ring, could be observed, whereas in polar and hydrogen-accepting solvents such as DMF, an inner 2H tautomer [P(2H)], having an outer NH, was predominant. These two tautomers differ largely in the electronic state and aromaticity, and this causes the remarkable change in the optical absorption and solution color. Recently, various factors like, solvent, substituent, concentration and isotope effect, affecting the NH tautomerism, have been confirmed by NMR measurements. Based on these studies, a possible reaction mechanism of the tautomerism will be discussed.

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Transient behaviors of aromatic ketones (ArK) such as benzophenone and aromatic hydrocarbons (ArH) such as naphthalene (NAP), dibenz[a,h]anthracene (DBA), and chrysene (CHR) in the higher triplet excited state (Tn) were investigated by two-color two-step excitation method using two ns-lasers. The first 355-nm laser generates ArK and ArH in the triplet excited state (T1) which can be subsequently excited to the Tn state. Energy transfer quenching of ArK(Tn) and ArH(Tn) was observed by quenchers (Q) with higher triplet energy than those of ArK(Tn) and ArH(T1) but lower than those of ArK(Tn) and ArH(Tn). From the effect of the Q concentration on the quenching efficiency, the lifetimes of ArK(S0) and ArH(Tn) were estimated. The second energy transfer from Q(T1) to ArK(Tn) or ArH(S0) was observed to occur at the diffusion-controlled rate. No evidence was observed for electron transfer from ArK(Tn) or ArH(Tn) to Q, although the electron transfer is possible to compete with the energy transfer quenching of ArK(Tn) and ArH(Tn) by Q according to the traditional electron and energy transfer theories. It was also found that ArK(Tn) and ArH(Tn) can efficiently induce scission of the halogen-carbon bond of Q such as carbon tetrachloride.

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Irradiation of an acetonitrile solution of 9-mesityl-10-methylacridinium ion (Acr⁺-Mes) results in formation of the long lived charge separated state via intramolecular electron transfer. The electron transfer dynamics was examined using the time-resolved fluorescence spectroscopy and ESR measurements. The intramolecular back electron transfer of the charge separated state was too slow to compete the intermolecular back electron transfer reaction.

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Macrocyclic and medium size stilbenophanes tethered by silyl chains were synthesized, and their photochemical properties were examined. Direct photoirradiation of a macrocyclic compound having two stilbene units and four dimethylsilyl groups in the ring gave intramolecular photocycloadduct stereoselectively, while triplet-sensitized photoreaction caused cis-trans photoisomerization of the stilben units. Photoreaction of cis-fixed medium size stilbenophanes under oxygen atmosphere gave the corresponding phenanthrenophanes. Absorption maxima of these stilbenophanes appeared at about 326 nm in dichloromethane, whose values were shifted to longer wavelength than that of unsubstituted trans-stilbene. Fluorescence quantum yield of the macrocyclic stilbenophane was larger than that of 4,4'-bis(trimethylsilylmethyl)stilbene. X-ray crystallographic analysis of the macrocyclic stilbenophane showed partially loss pf planarity of the stilbene units. The distance between two stilbene double bonds is about 7 angstrom, and the two stilbene units align like stairs.

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Triplet diphenylcarbene sterically protected by trifluoromethyl and bromo groups at ortho positions was found to be extremely stable, having a lifetime of 10 min in degassed benzene at room temperature. In order to prepare persistent triplet diphenylcarbene, diphenylcarbenes bearing aryl groups at ortho positions were generated by photolysis of the corresponding diazo compounds and were studied not only by product analysis and spectroscopic method but also by laser flash photolysis techniques. These studies showed that a lifetime of a diphenylcarbene bearing phenyl groups at the ortho positions was shorter than that of ortho-brominated diphenylcarbene due to a reaction between carbene-center and the o-phenyl group to afford fluorene derivative. In order to reduce the reactivity of the o-phenyl group, diphenylcarbenes having 3,5-bis(trifluoromethyl)phenyl or 4-biphenylyl groups were also generated.

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2-Silyl group effect on the reactivity of cyclopentane-1,3-diyl has been investigated in detail. Theory predicts that (1) the 2,2-disilyl 1,3-diradicals possesses the singlet ground state spin-multiplicity and (2) the paired electrons are occupied preferentially in the antisymmetric NBMO (Ψ_A). Thus, the silyl-substituted singlet cyclopentane-1,3-diyl is expected to give not the intramolecular cyclization product, but the silyl-migration product. Indeed, the experimentally generated 2-silylcyclopentane-1,3-diyl affords quantitatively the 5-silylcyclopentene derivative.

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On irradiation of p-chloranil (CA), 2,2-bis(p-methoxyphenyl)-3,3-dimethyl-4-methylenecyclobutanone (1) gives 2,2-bis(p-methoxyphenyl)-4-isopropylidenecyclobutanone (2), whereas 2 affords a CA adduct (4), suggesting that a novel rearrangement of 1 to give 2 occurs irreversibly via a radical cation intermediate of 3, a radical cation variant of an unprecedented oxa-analog of tetramethyleneethane.

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Thermolysis of trimethylsilylethynyl alkyl ether is known a method to make anisolabletrmethylsilylketene via 1,5-shift of the hydrogen atom on the β-carbon. The effect of introductionof a phenyl group on the alkyl group will be discussed.

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Most chemical reactions in solution are influenced by the coexisting solvent and salt. However, the role of solvent or ion has not been studied on the basis of the microscopic structures. Here we report that the solvent and the salt effects can be studied on the basis of the cluster structures observed through the mass spectrometry. The solvent effect on the self-association of alcohol molecules and the salt effect on the DNA replication are explained in relation with the cluster structures formed in the solution.

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We have first observed clusters for solvated cyclopentadienide ions (Cp-(solvent)_n)and Na⁺ ions (Na⁺(solvent)_m) which were isolated from polar solvents (DMSO, DMF, THF etc.)-CH₃CN solutions by using a specially designed mass spectrometer and found the clear-cut essential features concerning the solvation structure around Cp^- and Na⁺.

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In non-polar solvents, primary and secondary amines undergo self-aggregation, the predominating contributor is the dimeric amine. Several authors attribute this dimer as the crucial nucleophile in aminolyses of carboxylic esters as well as in S_NAr reactions in these solvents. The present authors undertook the probe reactions with aniline in benzene. Kinetic data can be reproduced in a dimer-nucleophile framework. A necessary condition of the dimer-nucleophile mechanism is that, as the aggregation is a preequilibrium in the reactions, a sole and a common equilibrium constant should be held for an amine in a given solvent at a given temperature irrespective of the change of reaction substrates.In S_NAr reactions with 2,4-dinitrohalobenzenes and 2,4,6-trinitrohalobenzenes, however, no unique and a common formation constant for aniline dimer can be derived. (scatter between 1.17 and 0.00232 mol^-1 dm³)In Michael addition-elimination reactions of ethyl trifluoroacetylvinyl ether, a formation constant for aniline dimer (3.68 mol^-1 dm³) can be derived, which again would not coincide with those found in S_NAr reactions. One is now in a position to look for an alternative mechanism that accords with the kinetic data hitherto obtained and the data for the reactions with phenyl trifluoroacetylvinyl solfone which are to be given in this work.

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The substituent effects on the solvolysis of 2,2-dimethyl-1,1-diphenylpropyl system were analyzed by the Yukawa-Tsuno equation and discussed in terms of changing coplanarity of two aryls in the transition state.In the 1,1-diaryl system where X=Y, the carbocationic transition state adopts a propeller-like twisted E-conformation to minimize steric repulsion, while in unsymmetrical (X is not equal to Y) ones the propeller shape is distorted. It is considered that in the present a-t-Bu system carbocationic species adopt extremely twisted conformation owing to steric hindrance of t-Bu group.The result of ab initio calculation of the carbocation-intermediate shows as follows. The symmetrically disubstituted carbocation(X=Y) adopts E-conformation where both aryls are equivalently twisted for the whole range of substituents. The carbocation (X is not equal to Y), when the variable substituents X are far more electron-donating than the fixed Y, takes a P_XT_Y-conformation where X-phenyl being coplanar and Y-phenyl being orthogonal. On the other hand, when variable X-substituents are far less activating than the fixed Y, the carbocation takes a P_YT_X-conformation. Consequently, this system is ideal for considering the conformational dependence of substituent effects.

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It is well known that the β-silicon substituent greatly facilitates the heterolysis of the C-Lg bond by 10¹²-fold, which is caused by the trimethylsilyl group in an antiperiplanar conformation. The β-silicon effect has been explained in terms of either the open form that is stabilized by σ-π-hyperconjugation, or the Si-bridged form by Si-participation. We thought that these two mechanisms can be distinguished by the position of Si atom, i. e., estimation of charge by means of substituent effects of Si-aryl ring. In this work, the substituent effects on the solvolysis rates of aryl-substituted derivatives [Ar-SiMe₂-CR₄R₃-CR₁R₂L where (R₄ = R₃ = R₂ = H), (R₁ = H, t-Bu, m-CF₃-Ph, Ph), L = Leaving group] in 60% aq. EtOH at 50°C were analyzed by the Yukawa-Tsuno Equation. The congested α-tBu system was found to indicate an intermediate ρ value of -1.47 between the open-cation system (ρ = ca. -1.00 for R₁ = Ph, m--CF₃-Ph) and the Si-bridged system (ρ = -1.75 for R₁ = H). Since the ρ value is changing continuously, it is concluded that the mechanism of β-silicon effect can be described as a continuous spectrum of transition state between the open cation and the Si-bridged cation based on the continuous change in the ρ value.

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The solvolysis rates of 1-(Diphenylmethylsilyl)-2-propyl 3,5-dinitrobenzoate was measured conductimetrically in aq. ethanol, aq. methanol, aq. acetone and aq. 2,2,2-trifluoroethanol at 55 °C and the solvent effect was analyzed in term of modified Winstein-Grunwald equation. The plot of log(k/k₀) vs Y_OTs was not correlated with all solvent systems and showed the dispersions between the correlation lines and the aq. acetone line was plotted above aq. ethanol line. The plot of log(k/k₀) versus Y_Δ+Y_OTs also gave less reliable correlation for all solvent systems. The above result suggests that the hydrophobic effect is one factor for the dispersions between solvent systems for the present β-Silicon compound.

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Since many organic reactions proceed in solvent, it is important to determine theoretical σ⁺ values for solution phase. For this purpose, it is necessary to know appropriate solvation models which reproduce the stabilities for the standard system of α-cumyl cations in solution. In this point of view, stabilities of α-cumyl cation coordinated by water molecule(s) (n=1-6) at cationic center were determined by means of hydride transfer reactions between ring substituted and unsubstituted cations. Energies for all species were calculated at the MP2/6-31G*//RHF/6-31G* level using Gaussian 98 program. The Yukawa-Tsuno analyses for the stabilities of hydrated α-cumyl cation with theoretically determined gas phase sigma values gave excellent linear correlations. While the r value didn't change so much, the absolute rho value decreased significantly with the number (n) of the water molecule down to 50% for the n = 6 system. When the substituent effect for this system was correlated with Brown and Okamoto's σ⁺ which is determined in solvolysis, deviations from the correlation line were observed for m-MeO and p-OH, indicating that specific solvation to the particular substituents is also important as a factor of appropriate solvation model.

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A detailed analysis for the mechanism of unimolecular heterolysis is discussed in terms of a modified Grunwald-Winstein equation: log k = m₀Y + Δ, where m₀ is an intrinsic sensitivity of a given substrate determined for non-aqueous solvents and Δ is a correction term for hydrophobicity of the substrate defined as the difference in the logarithmic rate constant in pure water between the observed value and that predicted from a correlation line for non-aqueous solvents. Ionization with the transition state structure close to intimate ion pair, solvent-separated ion pair, and free ion is each characterized by an m₀ value of 1.00, 1.73, and 2.07, respectively, for the chloride solvolysis.

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Solvent effects on solvolytic reactivity were analyzed for t-butylbis(trimethylsilyl)methanesulfonate and related substrates in terms of a modified Grunwald-Winstein equation, log k = m₀Y + Δ, where m₀ was intrinsic sensitivity determined as a slope for non-aqueous solvents and Δ was a hydrophobic factor determined as a difference in the rate constant in pure water in log unit between the observed value and the one predicted from the correlation line for organic solvents. The substrate was characterized by an m₀ value of 0.75, significantly smaller than that for the chloride, and a distinct effect of solvent nucleophilicity.

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We prepared β-arylethyl triflates having electron-withdrawing substituent on α or β position in order to study the effect of electron-withdrawing substituent on solvolses mechanism and reactivity. In this paper, solvolyses of α-COMe-β-phenylethyl triflate is reported. The reactions were followed by ¹H- and ¹⁹F-NMR. Though migrated products is main, unmigrated product is also obtained by S_N2 reaction. The migrated return ester is obtained too and the acetolysis rate of β-COMe-β-phenylethyl triflate was determined by non-linear least square analysis of the time profile. The acceleration effect which canceled the deceleration effect by the electron-withdrawing was observed as well as α-cyano group. Activation energy of these reactions was calculated by ab-initio method and discussed.

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It is known that the phenonium ion intermediate is formed in the solvolysis of β-arylethyl triflate. The aryl assisted acetolysis rate of α-CN,α-CF₃-OTf solvolysis with two electron-withdrawing groups was equivalent to that of α-CF₃-OTf. It is considered that these are two acceleration effects, that is, stabilization of cationic transition state by the electron releasing resonance of -CN and, unstabilization of the ground state by the geminal interaction between its groups and leaving group. In the present study, α,α-diCF₃-OTf without the inverse electron releasing resonance in the reaction center was synthesize and the solvolyses were examined. In the acetolysis of some substituted α,α-diCF₃-OTf, aryl-migrated β,β-diCF₃-OAc and aryl-unmigrated E2 product were formed. The acetolysis rate of α,α-diCF₃-OTf was faster than predictive value by the additivity. It is considered that the causes are unstabilization of the substrate by geminal interaction and steric unstabilization of the substrate. Substituent effect analysis and molecular orbital calculation of the stability are reported.

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It is known that the phenonium ion which has specific bridged structure is formed in the solvolysis of ester having aryl group at β position of reaction center. In our laboratory, we introduce electron-withdrawing groups (CF₃ etc.) at α or β position of reaction center and investigate the effect of them to reaction mechanism, reaction rate, and stability of phenonium ion. The acetolysis of triflate which has electron-withdrawing group, CF₃, at α or β position was observed great retardation effect. The retardation effect of β-CN group is equal to β-CF₃ group, that is, the electron withdrawing ability is equal. However α-CN-OTf didn't show the retardation equal to α-CF₃-OTf. It is considered that the causes are stabilization of phenonium ion type transition state by the inverse electron releasing resonance of CN and destabilization of the ground state by geminal interaction of CN. In this paper, we examined the effect of -COOMe group which has π electron system analogous to CN and is important in organic synthesis. As a result of measurement, large acceleration was observed in α-COOMe as well as α-CN group.

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The electrophilic abstraction of chloride ion by SbCl₅ from diphenylchlorborane in CD₃NO₂ resulted in a transient species that was followed in situ by ¹¹B and ¹³C NMR spectroscopy. ¹¹B NMR chemical shift (20.0 ppm) of the species downfield from BF₃-etherate reference was indicative of the formation of diphenylboron cation stabilized by O donor of two nitromethane molecules, i.e., solvated diphenylboron cation. Addition of two equivalent of pyridine to the solvated cationic species moved ¹¹B NMR chemical shift to 11.0 ppm, which is typical for four coordinate boronium salt. However, the reaction of diphenylchlorborane and one equivalent of pyridine in CD₃NO₂ gave only adduct species showing similar ¹¹B chemical shift of boronium salt (sp³). Reaction of this adduct with SbCl₅ as chloride acceptor caused ¹¹B chemical shift considerably downfield (31 ppm), resulting in three coordinate diphenylboron cation with N-ligand of pyridne (sp²). This borenium cation was then treated with one equivalent of pyridine to give the above boronium salt. An ab initio calculation of the ¹¹B chemical shift has been done by GIAO-HF/6-311+G(2d,p)//B3LYP/6-31+G(d)). The experimental ¹¹B chemical shift was in good agreement with the calculation result.

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Solvolysis of cyclohexylidenemethyl(phenyl)iodonium tetrafluoroborate was carried out in 2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoropropan-2-ol (HFP) in the presence of base. The reaction is much faster in TFE than in HFP. Products in TFE include solely un-rearranged enol ether 2 together with iodobenzene, while the main product in HFP is ring-expanded 1-alkoxycycloheptene 3. Results show that 2 is formed via α-elimination with alkylidenecarbene as an intermediate, while the reaction in HFP to give 3 involves a cycloheptyne intermediate that is mostly derived from an intermediate cyclohept-1-enyl cation via the E1-type pathway.

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Reaction of cyclohexenyliodonium salt with cyanide in chloroform gave vinylic and allylic cyanide products. Product analyses and deuterium labeling experiments suggest that the vinylic cyanide is obtained via cyclohexyne and that the allylic substitution reaction proceeds via Michael addition of cyanide to the iodonium, followed by elimination of iodonio group and 1,2-H shift. The Michael addition also occurs during thre reactions of of cyclopentenyliodonium salt with acetate and cycanide ions.

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Alkylidenecyclopropanone silylacetals undergo the ring-opening reaction under acidic conditions. The vinylic bond was cleaved to give nucleophilic substitution products via allylic cation intermediate. When the silyl acetal was treated with fluorid ion, allylic bond cleavege occured via carbanion intermediate.

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An optically active [4 + 2] adduct (up to 84% ee) is obtained from tetrachloro-1,2-benzoquinone and 1-alkoxy-4-phenylnaphthalene via photoinduced electron ransfer. The stereoselectivity suggests that the chiral side chain of naphthalene nucleophilically interacts with the naphthalene radical cation. The interaction was also detected by circular dichroism spectrum of the radical cation.

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Cycloheptatriene analogues are known to react with 4-phenyl-1,2,4-triazole-3,5-dione (PTAD) as there two tautomeric forms; cycloheptatriene and norcaradiene. In addition to those [4+2] additions, [2+2], [6+2], and ene additions are known to occurred. In this study, the reaction of a 7,7-dimethylcycloheptatriene having a chiral alcohol moiety at the 3-position and PTAD was found to be highly regio- and stereoselective to result in [4+2] addition at the cycloheptatriene tautomer. The nmr measurement at -78 °C disclosed that the primarily product is not that adduct, but a [2+2] adduct at the 3,4-position. The stereoselectivities for the formation of the both adducts depend on the solvent and the existence of the hydroxy group at the chiral alcohol moiety. In contrast, tetracyanoethylene of a weaker dienophile reacts at the norcaradiene tautomer. The stereoselectively of the addition is not high, but shows characteristic change by the solvent used. The result with other dienophile are also presented.

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The mechanism of regioselective Michael addition of thiols to unsymmetric fumaric derivatives was investigated. The competitive reaction between tert-butyl acrylate and ethyl acrylate indicated that ethyl acrylate underwent much faster addition by 4.4 times than tert-butyl ester. The rate difference was enhanced to 8.4 times by the presence of lithium cation. The presence of base promoted the Michael addition to acrylate ester much faster than acrylamide, while the absence of base prompted the addition to amide very much. PM3 calculation for fumaric esteramide showed C2 position, which is beta-carbon to the ester group, was activated to the nucleophilic attack. The amide group in the protonated esteramide was activated by the contribution of iminiumion intermediate, which prompted the addition to C3 carbon, the beat carbon to the amide group, exclusively.

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The temperature effect on the regio- and stereo selectivity in the [2+2] phetocycloaddition of carbonyl compounds (benzaldehyde, benzophenone) with unsymmetrically substituted fruns (2-methylfrun, 3-methylfrun) has been investigated to clarify the reaction mechanism. The regioselectivity (double-bond selection) for the reaction with benzaldehyde is not largely dependent on the temperature. The Eyring plot is found to be linear. In contrast, the regioselectivity for the reaction with benzophenone is found to be largely dependent on the temperature. The Eyring plot is not linear. The unusual non-linearity of the Eyring plot is accessed by the difference of the conformational distribution of the intermediary triplet 1,4-diradicals.

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Oxidation of allyl phenyl selenides with m-chloroperbenzoic acids(mCPBA) afforded addition products of m-chlorobenzoic acid(mCBA) and diols rather than allyl alcohols. In order to investigate the mechanism of formation of these products, the oxidation reaction was carried out under various conditions. The oxidation with tBuOOH or with mCPBA in the presence of triethylamine gave the corresponding allyl alcohols, while that with tBuOOH in the presence of mCBA gave the addition products. The reactions were also carried out with purified mCPBA in the absence or presence of water to observe the distribution of diol products. These results reveal that the oxidation under acidic and neutral conditions produces addition products and allyl alchohols, respectively. The presence of a significant amount of water is important in the formation of the diols.

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Reactionsa of the α-anion of anti-apicophilic C-apical O-equatorial spirophosphorane (O-cis) with electrophiles were examined. O-cis isomer reacted with PhCHO to form adducts instead of olefins, while Wittig type reaction took place to afford olefins quantitatively in the reaction of corresponding O-apical C-equatorial (O-trans) isomer. X-ray analysis of a hexacoordinate intermediate bearing an oxaphosphetane ring in the reaction of O-cis isomer was successful.

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We investigated π-facial selectivity in the Diels-Alder reaction of cross-conjugated ketones bearing a spiro-ring (spiro-lactone 1, spiro-ether 2, spiro-ketone 3) with dienes. Treatment of spiro lactone 1 with 2,3-dimethyl-1,3-butadiene and 1,3-cyclohexadiene afforded only single adducts of which was endo for the latter. The products resulted from attack of the dienes to the face bearing the oxygen atom of the oxa-spiro-ring. Treatment of dienones 1-3 with cyclopentadiene afforded a mixture of two endo-adducts. The Diels-Alder reaction of dienones 1,2 with cyclopentadiene in CH₂Cl₂, CH₃CN, CF₃CH₂OH afforded preferentially the adducts which resulted from reaction of the face of the dienophile bearing the spiro ring oxygen atom(6.5:1-29:1). The Diels-Alder reaction of dienones 1,2 with cyclopentadiene was accelerated in CF₃CH₂OH. When CH₃CN was used as a solvent, the facial selectivity in the Diels-Alder reaction of dienones 1,2 with cyclopentadiene slightly decreased. Both yield and π-facial selectivity in the Diels-Alder reaction of spiro-ketone 3 was very low relative to that of the reactions of dienones 1,2. Theoretical calculations imply that the dipole moment of the transition states and products, and orbital perturbations explained in terms of the Cieplak model may all contribute to the observed selectivities.

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Liquid crystalline materials generally possess a 1,4-disubstituted cyclohexane skeleton as a common structural component. And it is well-known that the commercially available process for the synthesis of these compounds produces a mixture of cis- and trans-isomers, but only the trans-isomers are useful as liquid crystalline materials. Therefore, it is hopefully required to find an effective method to isomerize cis-isomers into the corresponding trans-ones. Fortunately, we found that this type of isomerization was efficiently promoted by addition of TfOH. The general scope of this reaction will be reported.

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Tsuji found a reaction that acylsilane can act as a good reagent of acylation for allylester activated by a Pd complex. Detailed experimental studies proved the reaction does not proceed without trifluoroacetic acid instead of a simple acid such as acetic acid. As the reaction is very interesting and important to obtain α,β-unsaturated ketones, the mechanism of the reaction has not understood. In the present study, we investigated the mechanism of the reaction in detail by use of Density Functional Theory (DFT) calculations at the B3LYP/LANL2DZ level of theory. It was confirmed that the reaction proceeds via a TS with a trigonal bipyramid geometry around the trimethylsillyl fragment in the Pd complex. The stability of the binuclear Pd complex, which is a precursor for the catalytic reaction, is the key for importance of trifluoroacetic acid.

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The aim of our study is to elucidate the difference in the reaction mechanisms, S_N1 and S_N2, from the standpoint of quantum chemistry. In the S_N1 mechanism, the first step is a slow ionization of the substrate and the second is a rapid reaction between the intermediate carbocation and the nucleophile. The ionization is always assisted by the solvent. Therefore, the existence of the solvent molecules is essential to the S_N1 type reaction. We have carried out the ab initio MO calculations for alkyl halide/halide substitution reactions, Cl-CR₃ + Cl^- (R=H or CH₃), in the gas-phase and also in aqueous solution. In the gas-phase calculations, it was found that the variations of molecular orbitals along the reaction processes depend on the numbers of methyl substitution. We have obtained the free energy profiles in aqueous solution, using the statistical perturbation method based on Monte Carlo simulation with QM/MM method. The solute molecules are treated as QM (ab initio MO), and 100 water molecules (solvent molecules) are treated as MM (TIP3P). The calculated activation free energy of the halide substitution reaction of methylchloride is higher in water than in gas-phase.

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We have reported previously an example of dynamics-driven reaction pathway, in which ab initio MD trajectory shows a different pathway from the intrinsic reaction coordinate on the potential energy surface. Thus, for the intramolecular rearrangement of pinacolyl system, the MD trajectory suggested a stepwise pathway whereas a concerted mechanism was suggested by IRC. Such dynamics-driven reaction pathway can be viewed as resulting from asynchronicity of two reaction modes, in this specific case the C-O stretching and C-C-C bending modes. Similar phenomena may occur in many other organic reactions, in which multiple intramolecular or intermolecular modes are involved in the reaction coordinate. Generality of such mode asynchronicity will be discussed for various types of reactions, including the Beckmann rearrangements and proton transfer reactions on the basis of MO and MD computations.

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A high diasteroselectivity in pyrrolidinone enolate alkylations was previously studied using enolate anion as a model. Houk et al. Proposed that torisional strain between reagent and β-hydrogen and steric effects should control diastereo selectivity. Meyers et al. proposed that the π-facial difference in FMO extension in the ground state should control diastereoselectivity. We investigated possible enolate species of the enolate system in THF using the PCM method. Recently, we have proposed that the origin of this selectivity may be the populations of the initial complexes and that the torsional strain in the transition state is not important, based on the calculation performed in gas phase and PCM method. But the dielectric continiuum methods (PCM etc.) have been criticized as less sensitivity near the solute. Therefore we employed the cluster model using dimethylether (as the calculation model) for both the ground state and the transition state of pyrrolidinone enolate. The number of solvent coordination is one, and it was strongly suggested that selectivity may be controlled by the population of the most stable lithium enolate isomer (3).

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Carbocations derived from polycyclic aromatic hydrocarbons (PAHs) represent models for their biological activation via oxidative pathways that produce epoxides, dihydro-diols (proximate carcinogens) and diol-epoxides (ultimate carcinogens). We report the DFT calculations for the arenium ions of protonation and the two-electron oxidation dications derived from benzo[a]pyrene (BaP) and three of its nonalternant isomers azuleno[5,6,7-cd]phenalene (a strong carcinogen reported to be as potent as BaP) azuleno[1,2,3-cd]phenalene (a strong mutagen/weak carcinogen), and azuleno [4,5,6-cd]phenalene (a weak mutagen).

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