A tandem mass spectrometric study of a series of secondary amides of acetylglycine and hippuric acid utilizing electrospray ionization (ESI) was conducted. Among the fragment ions observed was an unusual one, which we have determined to be a nitrilium ion having the structure CH3-C≡N⊕-Ph or Ph-C≡N⊕-Ph by loss of the full mass of glycine as a neutral fragment. A mechanism that we propose involves an initial protonation of the oxygen atom at the N-terminus, followed by cyclization to a five-membered imidazolium ring, and its subsequent collapse to the nitrilium ion. This mechanism is supported by extensive isotopic labels and considerable variation of substituents. A similar study of the amides of acyl β-alanine and acyl γ-aminobutyric acid revealed that the former furnishes the same nitrilium ion, but not the latter. Thus, a six-membered intermediate is also possible and capable of losing the full mass of β-alanine as a neutral fragment. When the size of the ring is forced to be seven-membered, this pathway is blocked. When this study was expanded to include a variety of N-acylproline amides, the nitrilium ion was observed in 100% abundance only when the acyl group was acetyl. Thus a proline effect (involvement of a strained bicyclic [3.3.0] structure) is being observed.

The title reaction was investigated by the use of ONIOM-RB3LYP calculations. A reaction system composed of alpha-chlorocyclohexanone, a methoxide ion and 8 MeOH solvent molecules was adopted. Two reaction channels, the semibenzilic acid mechanism (A) and cyclopropanone mechanism (B), were compared. B is found to be more favorable than A. The rate-determining step of B is the (MeOH)(3) addition transition state (TS3B) to the cyclopropanone intermediate. While TS3B involves a concerted function of MeO(-) addition and proton relays, it has a large activation energy. A new route was found, where the chloride ion evolved at the cyclopropane formation step (TS2B) works as a nucleophile to the cyclopropanone intermediate. Thus, a cyclopentane-carbonyl chloride intermediate is formed with a small activation energy. A new cyclopropanone mechanism is proposed.

The neopentyl and the pinacol rearrangements as examples of Wagner-Meerwein rearrangements were investigated by the use of DFT calculations. As the first reaction, a model of neopentyl chloride (1b) and (H(2)O)(12) was employed. In the reaction, the patterns of C--Cl scission, methyl migration, and C--OH formation were analyzed. The calculations have shown that the 2-methyl-2-butanol (6) is formed in two steps with the transient intermediate, neopentyl alcohol (3). The first step is the nucleophilic substitution reaction and is the rate-determining one. The second step is the dual migration of methyl and OH(2) groups. The primary and tertiary carbocations were calculated to be absent in the neopentyl rearrangement starting from the hydrolysis. As the second reaction, the pinacol rearrangement of two substrates 2,3-dimethyl-2,3-butanediol (7) and 2,3-diphenyl-2,3-butanediol (12) was investigated. Acidic aqueous solvent was modeled by H(3)O(+) and 12H(2)O. The reaction paths were promoted by a hydrogen-bond circuit of H(3)O(+)(H(2)O)(2) and were determined as completely concerted processes. Protonated species and carbocations as intermediates also do not intervene during the pinacol rearrangement. Active functions of proton relays along the hydrogen bonds in the two rearrangements were demonstrated.(c) 2007 Wiley Periodicals, Inc. J Comput Chem, 2007.

Reaction paths for the title rearrangement along with its methyl analogue were investigated by density functional theory calculations. The reaction model is R-CO-CO-R + OH(-)(H(2)O)(4)--> R(2)C(OH)-COO(-)+(H(2)O)(4)(R = Me and Ph), where the water tetramer is employed both for solvation to OH(-) and for the proton relay along hydrogen bonds. The reaction is composed of OH(-) addition, C-C rotation, carbanion [1,2] migration, and proton relay toward the product anions. The rate-determining step was calculated to be the carbanion migration. Apparently, carbanion [1,2] migration is unlikely relative to the carbonium ion one. However, LUMOs of the 1,2-diketones have large and nodeless lobes at the reaction center, the C(1)-C(2) bond. The specific LUMO character is reflected both in the [2+1]-like one-center nucleophilic addition and in the carbanion [1,2] shift. The proton relay involved in the isomerization from the oxo intermediate to the carboxylate was calculated to take place via the water tetramer.

Tautomerization of purine in the water cluster was investigated by the use of DFT calculations. The correlation between the reaction paths and the number of water molecules (n) was examined. For n=3 and n=4, concerted reaction paths were obtained. However, for n=5, a stepwise path including an ion pair intermediate was found with small activation energies. The n=4+3 and n=4+3+9 models were calculated to give further small activation energies, where n=4 constitutes the reaction center and +3 and +3+9 denote the number of catalytic water molecules. The combination of the in-plane deprotonation at the N9 site and the out-of-plane protonation at the N7 site makes the n=4 model probable. Three protonated n=4+3+9 routes, a, b and c, composed of purineH+(H2O)4+3+9 were investigated. The n=4+3 moiety is also included in the three routes, and the route c (with the N1 protonation) was found to be most favorable. The purine tautomerization was found to involve the Zundel cation in the ion pair intermediate.

Through variable-temperature solution-state NMR and molten- and solid-state CP/MAS (13)C NMR spectra, thiotropolone is found to exist as two rapidly equilibrated tautomeric structures, thione and enethiol, even in the solid state far below the melting point. The crystal structure shows an almost perpendicular packing, suggesting that the intramolecular hydrogen bond is dominant.

By the use of DFT calculations, the title rearrangement, Ph-NH-NH-Ph ()--> H(2)N-C(6)H(4)-C(6)H(4)-NH(2)(2), was studied for the first time. Although it is a classical reaction (found in 1862), its mechanism is almost entirely unknown. There are three complexities associated with this mechanism. The first is the various rate orders for substituted hydrazobenzenes. The second is the product distribution. The third is the result of the kinetic isotope effect which is difficult to interpret. A reaction model,,(H(3)O(+))(2) and (H(2)O)(10) was used to trace the reaction path. Two hydronium ions were included, because there are two nitrogen atoms in . In the paths of the main reaction,(H(+))(2)-->H(+)+ H(+), transient intermediates were found. Through their conversion, the second product, diphenyline (), was reached. For H(+), only the Claisen shift path was found, and the pi complex proposed by Dewar was not found. The absence is in accord with the kinetic result of Hammond and Shine. But the complex was revealed in the dimethoxyhydrazobenzene. Thus, while Dewar's pi complex was ruled out in 1950, it has been revived by the present calculations.

The Cannizzaro reaction ("RX C") and the benzoin reaction ("RX B") were investigated by density functional theory calculations. Reaction models (benzaldehyde)(2)+ X(-)+(H(2)O)(n)[for X(-)= OH(-)(RX C) n = 8, and for X(-)= CN(-)(RX B) n = 8 or n = 14] were adopted. Three transition states (TSs) were obtained for RX C, and the rate-determining step was confirmed to be the hydride shift. The single electron transfer path was also obtained, which is supported by the C-O(-)CH[double bond, length as m-dash]O attraction. In RX B, seven TSs were obtained. The CC bond formation TS, TS4(B), was found to be the rate-determining step. However, the carbanion-formation TS (TS3(B)) and the CN(-) release TS (TS7(B)) are also of large activation free energies (DeltaG(double dagger)s). The result DeltaG(double dagger)(TS4(B))>/=DeltaG(double dagger)(TS7(B)) approximately DeltaG(double dagger)(TS3(B)) was obtained with both n = 8 and n = 14 models. Proton relays along the linear hydrogen bonds are concerned with bond interchanges and promote well arranged and successive elementary processes in RXs C and B.

Density functional theory calculations were conducted on the title reactions with explicit inclusion of a variety of water molecules, H-CO-NMe2 + MeOH +(H2O)n --> H-CO-OMe + HNMe2 +(H2O)n. Geometries of transition states, reactant-like complexes and product-like ones were determined by the use of RB3LYP/6-31G(d) SCRF=dipole. Concerted paths were examined with n = 0-3. Their Gibbs activation energies are larger than the experimental value. Stepwise paths were also investigated with n = 2-4. The n = 4 model has the energy close to the experimental value. However, when the catalytic water molecules were added to the n = 4 one, the stepwise path was switched to the concerted one. A systematic comparison of the concerted path with n = 2 + 1, 2 + 2, 2 + 3, 2 + 4, 2 + 5, 2 + 4 + 4, and 2 + 5 + 5 models was made, and the water-dimer based reaction path was found to be most favorable. The contrast between the concerted path of the amide solvolysis (and hydrolysis) and the stepwise one of the ester hydrolysis was discussed in terms of the frontier-orbital theory.

Various Baeyer-Villiger (B-V) oxidation reactions were examined by density functional theory calculations. Proton movements in transition states (TSs) of the two key steps, the nucleophilic addition of a peroxyacid molecule to a ketone (TS1) and the migration-cleavage of O-O (TS3), were discussed. A new TS of a hydrogen-bond rearrangement in the Criegee intermediate (TS2) was found. The hydrogen-bond directionality requires a trimer of the peroxyacid molecules at the nucleophilic addition of a peroxyacid molecule to a ketone TS (TS1). At the migration-cleavage of O-O TS (TS3), also three peroxyacid molecules are needed. Elementary processes of the B-V reaction were determined by the use of the (acetone and (H-CO-OOH)n, n = 3) system. The geometries of the nucleophilic addition of a peroxyacid molecule to a ketone TS (TS1) and the migration-cleavage of O-O TS (TS3) in the trimer (n = 3) participating are nearly insensitive to the substituent on the peroxyacid. The directionality is satisfied in those geometries. The migration-cleavage of O-O TS (TS3) was found to be rate-determining in reactions,[Me2C=O +(H-CO-OOH)3],[Me2C=O +(F3C-CO-OOH)3], and [Me2C=O +(MCPBA)3]. In contrast, the nucleophilic addition of a peroxyacid molecule to a ketone (TS1) is rate-determining in the reaction,[Ph(Me)C=O +(H-CO-OOH)3].

Density functional theory calculations were conducted on the title reactions with explicit inclusion of a variety of water molecules. Concerted reaction paths were examined first in the reaction model, ester(H(2)O)(n)()--> MeCOOH(H(2)O)(n)()(-)(1)EtOH, with n = 1-4. Their Gibbs activation energies are much larger than the experimental value, and the concerted paths are unfavorable. Various stepwise paths were investigated, and the ester(H(2)O)(4) reactant gives a likely stepwise path. The n = 4 based reaction models, n = 4 + 5 and n = 4 + 12, were found to have similar proton-relay shapes with good hydrogen-bond directionality. The distinction of either the concerted or the stepwise path is described by the position of only one proton in the "junction" water molecule.

LynF prenylates, but the prenyl migrates: Schmidt and co-workers have demonstrated that LynF from Lyngbya aestuarii is a reverse O-prenyl transferase. However, a forward C-prenylated product is obtained through a non-enzymatic Claisen rearrangement. The elucidation of this unprecedented two-step process is a significant contribution to our understanding of the biosynthesis of complex macrocyclic peptides.

Quantum chemical computations (B3LYP/6-31+G(d,p)) were applied to examine the mechanisms of dyotropic rearrangements of spirolactones in order to assess whether these reactions are concerted. Mechanistic experiments, designed on the basis of the results of these calculations, support the conclusions derived from theory. In particular, Zn(II) salts or Brønsted acids induce stepwise dyotropic processes, whereas dyotropic rearrangements mediated by silyltriflates are concerted processes. Additional products isolated with Zn(II) salts support a stepwise process with a carbocationic intermediate. Furthermore, a facile Grob-type fragmentation emanating from both a tricyclic-β-lactone and a spiro-γ-lactone was identified.

In this article we present recent developments in (3+2) cycloadditions with special emphasis on 1,3-dipolar reactions involving azomethine ylides and alkenes possessing electron withdrawing groups. It is found that there is not a general mechanism for these reactions since both concerted aromatic [(π)4(s)+(π)2(s)] mechanisms and stepwise processes involving zwitterionic intermediates can be found. These computational models can be extended to analyse the role of chiral catalysts in these reactions in order to understand the nature of the catalytic cycle and the origins of chiral induction.

The effective molarity (EM) for 12 intramolecular S(N)2 processes involving the formation of substituted aziridines and substituted epoxides were computed using ab initio and DFT calculation methods. Strong correlation was found between the calculated effective molarity and the experimentally determined values. This result could open a door for obtaining EM values for intramolecular processes that are difficult to be experimentally provided. Furthermore, the calculation results reveal that the driving forces for ring-closing reactions in the two different systems are proximity orientation of the nucleophile to the electrophile and the ground strain energies of the products and the reactants.

Photochemical irradiation of an equimolar mixture of (eta(5)-C(5)H(5))Fe(CO)(2)SiR(3), FpSiR(3), and FpMe leads to the efficient formation of the silicon-carbon coupled product R(3)SiMe, R(3)= Me(3), Me(2)Ph, MePh(2), Ph(3), ClMe(2), Cl(2)Me, Cl(3), Me(2)Ar (Ar = C(6)H(4)X, X = F, OMe, CF(3), NMe(2). Similar chemistry occurs with related germyl and stannyl complexes at slower rates, Si > Ge>>>Sn. Substitution of an aryl hydrogen in FpSiMe(2)C(6)H(4)R' has little effect upon the rate of the reaction whereas progressive substitution of methyl groups on silicon by Cl slows the process. Also changing FpMe to FpCH(2)SiMe(3) dramatically slows the reaction as does the use of (eta(5)-C(5)Me(5))Fe(CO)(2) derivatives. A mechanism involving the initial formation of the 16e(-) intermediate (eta(5)-C(5)H(5))Fe(CO)Me followed by oxidative addition of the Fe-Si bond, accounts for the experimental results obtained.

A kinetic study of the interaction of the surfactant cetyltrimethylammonium (CTA(+)) with DNA was carried out in water and in salt (NaCl) solutions. The results can be explained in terms of a reaction mechanism involving two consecutive reversible steps. The first step corresponds to the union/separation of the surfactant with/from the DNA. The second step corresponds to a conformational change of the surfactant/DNA complex. The equilibrium constant, calculated from the forward and reverse rate constants of these steps, agrees with the results of a previous thermodynamic study.

Photolysis of gaseous o-nitrobenzaldehyde (o-NBA) with selected different excitation wavelengths (355-400 nm) is investigated, and the nascent OH radical is detected by the single-photon laser-induced fluorescence (LIF) technique. The relative quantum yield and rotational excitation of OH formation are found to be dependent on the excitation energy. The distributions of rotational, spin-orbit, and Lambda-doublet states are obtained at 355-400 nm by analyzing the experimental data. The OH radicals are found to be vibrationally cold at all photolysis wavelengths. The spin-orbit and Lambda-doublet states have nonstatistical distributions. To understand the dissociative process involved in the OH-generating channel, DFT calculations are performed. Based on both experimental and theoretical results, possible photolysis channels of o-NBA leading to the OH fragment are proposed and discussed.

The complex-formation equilibria of dimethyltin(IV), trimethyltin(IV) and tributyltin(IV) with pyridoxamine were investigated in dioxane-water mixtures and at different temperatures using a potentiometric technique. The stepwise formation constants of the complexes formed in solution were calculated using the non-linear least-square program MINIQUAD-75. The effect of dioxane as a solvent on the protonation constants of pyridoxamine and the formation constants of organotin(IV) complexes was discussed. The thermodynamic parameters DeltaH degrees and DeltaS degrees calculated from the temperature dependence of the equilibrium constants were investigated. The concentration distribution of the various complex species was evaluated as a function of pH.

The methods for thermodynamic calculations of the equilibria in solutions of mercury salts and complexes are presented. The calculations of equilibrium constants in non-aqueous solvents are based on the transfer activity coefficients of mercury ions from water to the non-aqueous solvent. The dismutation and precipitation reaction constants are calculated, and the redox potentials of mercury systems are measured. Examples of analytical use of the thermodynamic functions of mercury salt solvation are given in the text.

Density functional theory calculations were performed to study the ability of uranium cations, U (+) and U (2+), to activate the N-N and N-O bonds of N 2O. A close description of the reaction pathways leading to different reaction products is presented. The obtained results are compared with previous experimental works. The nature of the bonding of all the involved species and the bonding evolution along the reaction pathways was studied by means of the topological analysis of the ELF function.