A computational study into the reactivity of epichlorohydrin and epibromohydrin under acidic conditions in the gas phase and aqueous solution

Ab initio molecular orbital calculations have been carried out upon epichlorohydrin and epibromohydrin at the Hartree–Fock (HF) and Møller–Plesset (MP2) levels of theory to explore the reactivity of these species with respect to nucleophilic attack by water under acidic conditions in the gas phase and aqueous solution. These results suggest that nucleophilic attack occurs preferentially at the epoxy carbon atoms in both the gas phase and aqueous solution. These results are in contrast to those found for nucleophilic attack under basic conditions, where attack at the halocarbon atom is competitive with that at the epoxy carbon atoms. Copyright © 2007 John Wiley & Sons, Ltd.     

Understanding the stereo‐ and regioselectivities of the polar Diels–Alder reactions between 2‐acetyl‐1,4‐benzoquinone and methyl substituted 1,3‐butadienes: a DFT study

The polar Diels–Alder (DA) reactions of 2‐acetyl‐1,4‐benzoquinone (acBQ) with methyl substituted 1,3‐butadienes have been studied using DFT methods at the B3LYP/6‐31G(d) level of theory. These reactions are characterized by a nucleophilic attack of the unsubstituted ends of the 1,3‐dienes to the β conjugated position of the acBQ followed by ring‐closure. The reactions present a total regioselectivity and large endo selectivity. The analysis based on the global electrophilicity of the reagents at the ground state, and the natural bond orbital (NBO) population analysis at the transition states correctly explain the polar nature of these cycloadditions. The large electrophilic character of acBQ is responsible for the acceleration observed in these polar DA reactions. Copyright © 2008 John Wiley & Sons, Ltd.     

Nucleophilic reactivity of thiolate, hydroxide and phenolate ions towards a model O-arylated diazeniumdiolate prodrug in aqueous and cationic surfactant media

The kinetics of aromatic nucleophilic substitution of the nitric oxide‐generating diazeniumdiolate ion, DEA/NO, by thiols (L ‐glutathione, L ‐cysteine, DL ‐homocysteine, 1‐propanethiol, 2‐mercaptoethanol, and sodium thioglycolate) from the prodrug, DNP‐DEA/NO, has been examined in aqueous solution and in solutions of cationic DOTAP vesicles. Second‐order rate constants in buffered aqueous solutions (k_RS‐ = 3.48–30.9 M^?1 s^?1; 30 °C) gave a linear Brønsted plot (β_nuc = 0.414 ± 0.068) consistent with the rate‐limiting S_NAr nucleophilic attack by thiolate ions. Cationic DOTAP vesicles catalyze the thiolysis reactions with rate enhancements between 11 and 486‐fold in Tris‐HCl buffered solutions at pH 7.4. The maximum rate increase was obtained with thioglycolate ion. Thiolysis data are compared to data for nucleophilic displacement by phenolate (k_PhO‐ = 0.114 M^?1 s^?1) and hydroxide (k_OH‐ = 1.82 × 10^?2 M^?1 s^?1, 37 °C) ions. The base hydrolysis reaction is accelerated by CTAB micelles and DODAC vesicles, with the vesicles being ca 3‐fold more effective as catalysts. Analysis of the data using pseudo‐phase ion‐exchange (PIE) formalism implies that the rate enhancement of the thiolysis and base hydrolysis reactions is primarily due to reactant concentration in the surfactant pseudo‐phase. Copyright © 2009 John Wiley & Sons, Ltd.     

Theoretical evidence on O–N type smiles rearrangement mechanism: a computational study on the intramolecular cyclization of N‐methyl‐2‐(2‐chloropyridin‐3‐yloxy)‐acetamide anion

Smiles rearrangement (SR) falls under a broad category of organic synthesis for many important compounds. A complete understanding toward SR process appeals to the assistance of theoretical research. Herein, by performing quantum chemistry calculations, we give a theoretical evidence for the mechanism of a representative O–N type SR, the intramolecular cyclization of N‐methyl‐2‐(2‐chloropyridin‐3‐yloxy)acetamide anion. It is found that the SR to the ipso‐position involves a two‐step mechanism and is energetically more favorable than the direct nucleophilic attack by N atom on the ortho‐position. The present result rationalizes well the experimentally observed ipso‐SR product and provides a consistent picture of the O–N SR process. Copyright © 2008 John Wiley & Sons, Ltd.     

Computational (MP2 and DFT) modeling of the substrate/inhibitor interaction with the LDH active pocket in the gas phase and aqueous solution: bimolecular charged (pyruvate/oxamate–guanidinium cation) and neutral adducts (pyruvic/oxamic acids–guanidine)

Two types of bimolecular adducts were studied for the substrate and inhibitor of lactate dehydrogenase (LDH), one type of adducts between ionic species, α‐keto‐carboxylates (pyruvate and oxamate) and the guanidinium cation, and the other type of adducts between neutral species, α‐ketocarboxylic (pyruvic and oxamic) acids and guanidine. Calculations were performed in the gas phase and aqueous solution using the MP2 and PCM methods and the 6‐31++G** basis set. Application of the DFT(B3LYP) and PCM methods led to similar results. A change of the adducts' preference was observed when proceeding from the gas phase to aqueous solution. This change is in good agreement with the acidity–basicity scales in both phases. Formation constant (K_HB) for adduct between neutral species is greater for pyruvic than for oxamic acid in the gas phase, whereas a reverse situation takes place in aqueous solution, where the K_HB value for adduct between ionic species is smaller for pyruvate than for oxamate. The water molecules favor interactions of more polar oxamate with the guanidinium cation. Stronger interaction with this cation, a model of the arginine fragment of the LDH pocket, suggests that oxamate (inhibitor of LDH) has stronger binding properties in aqueous solution than pyruvate (substrate of LDH). Copyright © 2008 John Wiley & Sons, Ltd.     

Propanolysis of arenesulfonyl chlorides: Nucleophilic substitution at sulfonyl sulfur

We have studied the mechanism of solvolysis of arenesulfonyl chlorides by propan‐1‐ol and propan‐2‐ol at 303‐323 K. Kinetic profiles were appropriately fit by first‐order kinetics. Reactivity increases with electron‐donating substituents. Ortho‐alkyl substituted derivatives of arenesulfonyl chlorides show increased reactivity, but the origin of this “positive” ortho‐effect remains unclear. Likely, ortho‐methyl groups restrict rotation around the C‐S bond, facilitating the attack of the nucleophile. No relevant reactivity changes have been found with propan‐1‐ol and propan‐2‐ol in terms of nucleophile steric effect. The existence of isokinetic relationships for all substrates suggests a single mechanism for the series. Solvolysis reactions of all substrates in both alcohols show isokinetic temperatures (T_iso) close to the working temperature range, which is an evidence of the process being influenced by secondary reactivity factors, likely of steric nature in the TS. Solvation plays a relevant role in this reaction, modulating the reactivity. In some cases, the presence of t‐Bu instead of Me in para‐ position leads to changes in the first solvation shell, increasing the energy of the reaction (ca. 1 kJ·mol^?1). The obtained results suggest the same kinetic mechanism of solvolysis of arenesulfonyl chlorides for propan‐1‐ol and propan‐2‐ol, as in MeOH and EtOH, where bimolecular nucleophilic substitution (S_N2) takes place with nucleophilic solvent assistance of one alcohol molecule and the participation of the solvent network involving solvent molecules of the first solvation shell.     

Experimental and theoretical push‐pull Chemo‐ and regioselectivity in 1,3‐Dipolar cycloaddition reactions: the case of benzotriazepin‐5‐one with mesitylnitrile oxide

A novel heterocyclic compound 3‐mesityl‐5‐methyl‐4,5,11,11a‐tetrahydro‐6H‐[1,2,4]oxadiazolo [5,4‐b][1,3,4]benzotriazépin‐6‐one 4 has been synthesised by a 1,3 dipolar cycloaddition (13DC) reaction of 1,3,4‐benzotriazepin‐5‐one 1 with mesitylnitrile oxide 3 . The reaction, beside its synthetic interest, has shown to be completely chemo‐ and regioselective. The structure of the compound was determined by X‐ray crystallography and analysed by spectral methods (NMR and mass spectrometry). The molecular mechanism for the reaction has been studied using quantum mechanical calculations at the B3LYP/6‐31G* theory level. Two mechanisms are possible for the formation of the cycloadduct 4 . The first one involves a 13DC reaction between 1 , as dipolarophile and 3 , as dipole. Analysis of the results indicates that it takes place along asynchronous concerted bond‐formation process with a very low polar character. The regioselectivity obtained from the calculations are in complete agreement with the unique formation of the cycloadduct 4 . The second mechanism is initiated by the nucleophilic attack of the N3 nitrogen of the tautomer form of 2 , to the C5 carbon of the nitrile oxide 3 to yield an amidoxime. However, the large energy involved in this addition prevents this mechanism. The large energy difference between the tautomers 1 and 2 , makes that only the C?N site of benzotriazepin‐5‐one 1 could act as a dipolarophile site. This fact makes the 13DC reaction to be chemoselective. The analysis of global electrophilicity of the reagents allows explaining the low polar character of these 13DC reactions. Copyright © 2007 John Wiley & Sons, Ltd.     

Mechanism of the acidic hydrolysis of epichlorohydrin

The present studies show that the currently accepted scheme for the hydrolysis of epichlorohydrin (ECH) needs to be extended by an additional path which makes allowance for the formation and decomposition of glycidol (GL). It was shown experimentally and through UB3LYP/6‐11 + +G(3D,P) calculations that the formation of 3‐chloro‐1,2‐propanediol (MCPD) from ECH should also take into account GL formation as an intermediate product. A modified mechanism for the course of ECH hydrolysis in acidic and neutral medium is proposed. It was shown that ECH hydrolysis in acidic medium in the presence of chloride ions also results in the formation of 1,3‐dichloro‐2‐propanol (DCPD) in addition to GL and MCPD. The possibility of a parallel pathway for water molecule addition to epichlorohydrin was shown which as a consequence led to the parallel appearance of GL and MCPD. It was confirmed by kinetic calculations that the state of equilibrium, reached in the process of ECH chlorination, did not result in GL formation. However, its appearance in the reaction mechanism has been ignored in the literature thus far. Copyright © 2011 John Wiley & Sons, Ltd.     

Mechanism of sulfur transfer from 1,2,4‐dithiazolidine‐3,5‐diones to triphenylphosphines

The mechanism of sulfurization of substituted triphenylphosphines with 4‐(3‐ and 4‐substituted)‐1,2,4‐dithiazolidine‐3,5‐diones in acetonitrile, dichloromethane, tetrahydrofuran and toluene at 25 °C was studied. The reaction pathway involves rate‐limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate and carbonylsulfide. From the Hammett correlations and from the solvent dependency, it was concluded that the transition‐state structure is very polar and resembles the zwitter‐ionic intermediate. The extent of P–S bond formation and S–S bond cleavage is very similar in the solvents series, but the latter gradually decreases with the decreasing polarity of the solvent. Copyright © 2013 John Wiley & Sons, Ltd.     

Spectrophotometric Study of Catechol Oxidation by Aerial O2 in Alkaline Aqueous Solutions Containing Mg(II) Ions.

Electronic absorption spectroscopy was employed to study the aerial oxidation of catechol (1,2-benzenediol) in alkaline aqueous solution containing an excess of Mg(II) ions. Graphical analysis by the matrix method of UV spectra recorded at regular time intervals gave a good fit for two absorbing species in solution. Based on this result and our earlier ESR spectroscopic investigations we concluded that two main absorbing species in this system are Mg(II)-spin stabilized o-benzosemiquinone anion radical and C-C dimer formed by the nucleophilic attack of catecholate anion on o-benzoquinone. Although the formation of 1,2,4-benzenetriol during the catechol oxidation has been detected in some ESR studies its presence was not indicated by this analysis probably because of the low and/or stable steady state concentration throughout the experiment.     

Polymer track membranes for atmospheric pressure field extraction of ions from liquid solutions

An approach to the generation of gas phase ions by field extraction from liquid solutions has been investigated. The method uses a polymer membrane with nano-size channels as an interface between the liquid and the atmospheric pressure gas. Ions are produced by dissociation in the polar solvent and secondary ion-molecular reactions in the solution, which fills the channels of the membrane. Field extraction of the ions from the channels is stimulated by pulses of the electric discharge between the membrane and an adjacent electrode in the gas. The gas-phase ions are removed from the extraction zone by air flow and are detected by mass spectrometry. Possibilities of the membrane interface for generation of gas phase ions have been demonstrated from mass spectral investigation curried out for angiotensin II, gramicidin S and cytochrome C solutions. The current kinetics of the membrane ion source has been investigated to elucidate the mechanism of the ion extraction.     

The Internal Steric Push-Effect: Its Consequences on the Reactivity of Carbonyl Functions in 3-Substituted Phthalic Anhydrides

The enhanced reactivity of the meta carbonyl function vis-a-vis nucleophiles in 3-substituted phthalic anhydrides is interpreted in terms of an internal steric effect. A through-space interaction between the substituent and the carbonyl function causes a displacement of electrons in the C=O bond from the oxygen to the carbon atom with simultaneous deactivation of the carbon atom toward nucleophilic attack and the oxygen atom toward complexation with a counter ion.     

Kinetic study on the aromatic nucleophilic substitution reaction of 3,6‐dichloro‐1,2,4,5‐tetrazine by biothiols

The aromatic nucleophilic substitution reaction of 3,6‐dichloro‐1,2,4,5‐tetrazine (DCT) with a series of biothiols RSH: (cysteine, homocysteine, cysteinyl–glycine, N‐acetylcysteine, and glutathione) is subjected to a kinetic investigation. The reactions are studied by following spectrophotometrically the disappearance of DCT at 370 nm. In the case of an excess of N‐acetylcysteine and glutathione, clean pseudo first‐order rate constants (k_obs1) are found. However, for cysteine, homocysteine and cysteinyl–glycine, two consecutive reactions are observed. The first one is the nucleophilic aromatic substitution of the chlorine by the sulfhydryl group of these biothiols (RSH) and the second one is the intramolecular and intermolecular nucleophilic aromatic substitutions of their alkylthio with the amine group of RSH to give the di‐substituted compound. Therefore, in these cases, two pseudo first‐order rate constants (k_obs1 and k_obs2, respectively) are found under biothiol excess. Plots of k_obs1 versus free thiol concentration at constant pH are linear, with the slope (k_N) independent of pH (from 6.8 to 7.4). The kinetic data analysis (Brønsted‐type plot and activation parameters) is consistent with an addition–elimination mechanism with the nucleophilic attack as the rate‐determining step. Copyright © 2014 John Wiley & Sons, Ltd.     

Investigation of sorption phenomena by solid phase extraction and liquid chromatography for the determination of some ether derivatives of tetrabromobisphenol A

Observed sorption and chromatographic behaviour served as a starting point for the examination of four ether derivatives of the flame retardant tetrabromobisphenol A (TBBPA): dihydroxyethyl (DHEE), dimethyl (DMe), diallyl (DAE) and dibromopropyl (DBPE). To date, there is little or no information about these compounds in the scientific literature. The targets in the present study had calculated log K_ow values of 6.0–10. A broad range of different types of solvents were used in order to elucidate the mechanisms of sorption onto silica (glass) and two solid phase extraction cartridges based on polystyrene divinylbenzene polymers, hydroxylated (Isolute ENV+) and vinylpyrrolidone (Oasis HLB) containing units. Also, three chromatographic columns (C18, C8 and dual C18‐based, i.e. a polar ligand together with C18 on a silica surface) were evaluated. The following were observed: desorption of the targets from silica surface by 1‐propanol showed the best results and the yields were further improved by silylation of the surface. Regardless of the experimental test conditions applied, the lowest recovery was seen for the DMe derivative, followed by TBBPA itself, which had calculated log K_ow values in between the other targets. A washing solution containing up to 70% methanol could be used without elution of the targets from the solid phase extraction cartridge . The dihydroxethyl ether derivative of TBBPA is most probably not affected by environmental relevant pH due to a likely high pK_a (ca 15). Also, this study shows that the polar character of the dual‐phase column was not as pronounced as asserted by the manufacturer. Copyright © 2009 John Wiley & Sons, Ltd.     

Radical anions containing the dioxidated 1,2,5‐thiadiazole heterocycle

Radical anions of 3,4‐aryl disubstituted 1,2,5‐thiadiazole 1,1‐dioxide were obtained by chemical and electrochemical reduction of their substrates, and characterized by ESR spectroscopy and cyclic voltammetry. The radical anion of the phenanthro[9,10‐c]‐1,2,5‐thiadiazole 1,1‐dioxide was found to be very stable in an aprotic solvent solution and did not react readily when water was added to the aprotic solvent, or the solution was saturated with oxygen gas. The radical formation chemical reaction competed with nucleophilic addition to the C?N bond of the thiadiazoles. A possible reaction mechanism, and a common reaction intermediate, supported by density functional theory calculations, is presented for the most stable radical. Copyright © 2009 John Wiley & Sons, Ltd.     

Local structure investigation of the active site of the imidazolonepropionase from Bacillus subtilis by XANES spectroscopy and ab initio calculations

Imidazolonepropionase is an important enzyme that plays a crucial role in the degradation of the histidine in mammals and bacteria. In this contribution a detailed structural investigation is presented of the imidazolonepropionase from Bacillus subtilis at the zinc site by X‐ray absorption near‐edge structure (XANES) spectroscopy combining experimental data with ab initio calculation in the framework of the multiple‐scattering theory. The resolved local structure leads to a modification of the data set in the Protein Data Bank (PDB) (PDB code 2BB0). Actually, data suggest that the carboxyl of the Asp324 moves far away from the zinc ion at the center, while the water molecule and the nearest‐neighbor histidines move towards it. This new conformation and the occurrence of a short water‐to‐zinc bond length support the nucleophilic attack catalytic mechanism proposed for this enzyme.     

A molecular electron density theory study of the [3 + 2] cycloaddition reaction between an azomethine imine and electron deficient ethylenes

The selectivity and the nature of the molecular mechanism of the [3 + 2] cycloaddition (32CA) reaction of an azomethine imine (AI 12) with p‐nitrobenzylidenemalononitrile (NBMN, 13) have been theoretically studied within the Molecular Electron Density Theory using DFT methods at the MPWB1K/6‐31G(d) computational level. Analysis of the Conceptual DFT reactivity indices indicates that the strong nucleophilic character of AI 12 together with the high electrophilic character of NBMN 13 accounts for the strong polar character of this 32CA reaction, which demands very low activation energy. Analysis of the energy profiles indicates that this polar zw‐type 32CA reaction proceeds completely with a meta/exo selective pathway, in great agreement with the experimental data. Analyses of both molecular electrostatic potential and the non‐covalent interactions at the meta regioisomeric TSs allow explaining the observed exo stereoselectivity. Electron Localisation Function topological analysis indicates that the studied 32CA reaction takes place via a non‐concerted two‐stage one‐step mechanism as a [2n + 2τ] process.     

Experimental and molecular modeling investigation of (E)-N-{2-[(2-hydroxybenzylidene)amino]phenyl}benzenesulfonamide

The Schiff base compound (E)-N-{2-[(2-hydroxybenzylidene)amino]phenyl}benzenesulfonamide has been synthesized and characterized by IR, NMR and Uv-vis spectroscopies, and single-crystal X-ray diffraction technique. In addition, quantum chemical calculations employing density functional theory (DFT) method with the 6–311++G(d,p) basis set were performed to study the molecular, spectroscopic and some electronic structure properties of the title compound, and the results were compared with the experimental findings. There exists a good correlation between experimental and theoretical data. Enol-imine/keto-amine tautomerization mechanism was investigated in the gas phase and in solution phase using the polarizable continuum model (PCM) approximation. The energetic and thermodynamic parameters of the enol-imine?→?keto-amine transfer process show that the single proton exchange is thermodynamically unfavored both in the gas phase and in solution phase. However, the reverse reaction seems to be feasible with a low barrier height and is supported by negative values in enthalpy and free energy changes both in the gas phase and in solution phase. The solvent effect is found to be sizable with increasing polarity of the solvents for the reverse reaction. The predicted nonlinear optical properties of the compound are found to be much greater than those of urea.     

Polar regions in the paraelectric phase in a PbZr0.992Ti0.008O3 single crystal

Anomalous behaviour of ε and tan δ in the paraelectric phase was found for PbZr0.992Ti0.008O₃ single crystal. In the vicinity of temperatures 280–290°C (T _c = 236°C) the pyroelectric effect was also observed. Using the data obtained, the existence of an additional polarization (polar regions oriented in an external electric field) in the paraelectric phase is discussed.