Potential Energy Surface Diagrams Research Articles

A general, most basic rule for ion dissociation: Protonated molecules.

Contrary to the common but potentially misleading belief that when a protonated molecule is excited, it is its most stable protomer that will mandatorily dissociate, we demonstrate herein that, when rationalizing or predicting the chemistry of such ions, we should always search for the most labile protomer. This "most labile protomer" rule, based on the mobile proton model, states therefore that when a protonated molecule is heated, during ionization or by collisions for instance, the loosely bonded proton (H+ ) can acquire enough energy to detach itself from the most basic site of the molecule and then freely "walk through" the molecular framework to eventually find, if available, another protonation site, forming other less stable but more labile protomers, that is, protomers that may display lower dissociation thresholds. To demonstrate the validity of the "most labile protomer" rule as well as the misleading nature of the "most stable protomer" rule, we have selected several illustrative molecules and have collected their ESI(+)-MS/MS. To compare energies of precursors and products, we have also performed PM7 calculations and elaborated potential energy surface diagrams for their possible protomers and dissociation thresholds. We have also applied the "most labile protomer" rule to reinterpret-exclusively via classical charge-induced dissociation cleavages-several dissociation processes proposed for protonated molecules. In an accompanying letter, we have also applied a similar "most labile electromer" rule to ionized molecules.

Remdesivir: Mechanism of Metabolic Conversion from Prodrug to Drug.

Remdesivir (GS-5734) has emerged as a promising drug during the challenging times of COVID-19 pandemic. Being a prodrug, it undergoes several metabolic reactions before converting to its active triphosphate metabolite. It is important to establish the atomic level details and explore the energy profile of the prodrug to drug conversion process. In this work, Density Functional Theory (DFT) calculations were performed to explore the entire metabolic path. Further, the potential energy surface (PES) diagram for the conversion of prodrug remdesivir to its active metabolite was established. The role of catalytic triad of Hint1 phosphoramidase enzyme in P-N bond hydrolysis was also studied on a model system using combined molecular docking and quantum mechanics approach. The overall energy of reaction is 11.47 kcal/mol exergonic and the reaction proceeds through many steps requiring high activation energies. In the absence of a catalyst, the P-N bond breaking step requires 41.78 kcal/mol, which is reduced to 14.26 kcal/mol in a catalytic environment. The metabolic pathways of model system of remdesivir (MSR) were explored completely and potential energy surface diagrams at two levels of theory, B3LYP/6-311++G(d, p) and B3LYP/6-31+G(d), were established and compared. The results highlight the importance of an additional water molecule in the metabolic reaction. The PN bond cleavage step of the metabolic process requires the presence of an enzymatic environment.

Computational investigation of catalytic effects of CX3COOH (X = F,Cl,H) on the three-component cyclocondensation reaction.

The mechanism of acetic acid (AA), trifluoroacetic acid (TFA), and trichloroacetic acid (TCA) catalyzed three-component cyclocondensation reaction to (4S,6S)-4,6-diphenyl-1,3,5-triazinane-2-thione was determined via density functional calculations. Based on the potential energy surface diagram, TCA was found to be a reasonable catalyst [energy span (δG) is 2kcalmol-1 less than TFA and AA] for the reaction. An energetic span model implies that TFA and AA show the same catalytic performance. The impact of the presence of halogen atoms in TFA and TCA catalysts is quantified via energy barriers. Graphical Abstract Ranking catalytic efficiency of OTC triazinane-2-thione formation Graphical Abstract contains poor quality and small text inside the artwork. Please do not re-use the file that we have rejected or attempt to increase its resolution and re-save. It is originally poor, therefore, increasing the resolution will not solve the quality problem. We suggest that you provide us the original format. We prefer replacement figures containing vector/editable objects rather than embedded images. Preferred file formats are eps, ai, tiff and pdf.It is attached as tiff format.

ESIPT reaction of potential bioactive heterocyclic Schiff base: Atomic visualization coupled with in vitro spectroscopy

Abstract The present study epitomizes the identification of ground state geometry, determination of X-ray structure and solvent dependent excited state intramolecular proton transfer (ESIPT) process of a potential bioactive benzothiazole Schiff base ligand viz (E)-2-((6-chlorobenzo[d]thiazol-2-ylimino)methyl)-5-(diethylamino)phenol (CBMDP) using 1H and 13C NMR, FTIR, single crystal XRD, electronic absorption, steady state emission, time resolved and 3D-fluorescence spectroscopic techniques. The experimental observations have further been corroborated with quantum chemical calculations using Density Functional Theory (DFT) and Time Dependent DFT (TDDFT) methods. Single crystal X-ray structure confirms the existence of enol-imine (N) form of CBMDP in the ground state due to strong intramolecular hydrogen bond between phenolic hydrogen and azomethine nitrogen. The photophysical studies reveal that on photoexcitation, the molecule undergoes structural changes via ESIPT reaction. Dual emission have been identified from the excited enol-imine (N*) and tautomeric keto-amine (T*) species in non-polar heptane. The redistribution of the electron density in the photoexcited CBMDP molecule is visualised from DFT and TDDFT calculations. This electronic redistribution enhances the in basic character of azomethine nitrogen which is reflected in the Mulliken partial atomic charges increases from −0.21 to −0.56, which ultimately leads to an intramolecular hydroxyl proton transfer in the excited state. The simultaneous emission from two states are also theoretically supported by the low energy difference (0.66 kcal/mol) between the N* and T* form in the potential energy surface diagram. The consolidated spectroscopic research, described herein, provides enormous information to open up the new avenues in designing and synthesizing potential bioactive benzothiazole Schiff bases for medicinal chemistry research.

Multiscale Modeling of a Proton Exchange Membrane Fuel Cell: Atomistic Oxygen Reduction Reaction Model

In this work is presented a kinetic model for the oxygen reduction reaction (ORR), which is studied considering a dissociative mechanism and using electronic structure calculations. This model was developed to include it in a multiscale model for a Proton Exchange Membrane Fuel Cell (PEMFC). As result of this work the energetic properties and electronic structure properties of the system made up by the principal intermediates (O, O2, OH, H2O) and the Pt surface are calculated, also it is obtained the energy barriers for each step and the energy difference between products and reactants, allowing to construct the potential energy surface diagram for the complete oxygen dissociation mechanism. These results point out that the dissociation of adsorbed O2 is the reaction limiting step, it is associated whit the high adsorption energy of this molecule which is explained using electronic structure features as the local density of states. Also the calculated activation energies for the ORR cause an improvement of the phenomenological description of a PEMFC when they are used in a multiscale model.

C–H and C–C Activation of n-Butane with Zirconium Hydrides Supported on SBA15 Containing N-Donor Ligands: [(≡SiNH−)(≡SiX−)ZrH2], [(≡SiNH−)(≡SiX−)2ZrH], and[(≡SiN═)(≡SiX−)ZrH] (X = −NH–, −O−). A DFT Study

Density functional theory (DFT) was used to elucidate the mechanism of n-butane hydrogenolysis (into propane, ethane, and methane) on well-defined zirconium hydrides supported on SBA15 coordinated to the surface via N-donor surface pincer ligands: [(≡SiNH−)(≡SiO−)ZrH2] (A), [(≡SiNH−)2ZrH2] (B), [(≡SiNH−)(≡SiO−)2ZrH] (C), [(≡SiNH−)2(≡SiO−)ZrH] (D), [(≡SiN═)(≡Si–O−)ZrH] (E), and [(≡SiN═)(≡SiNH−)ZrH] (F). The roles of these hydrides have been investigated in C–H/C–C bond activation and cleavage. The dihydride A linked via a chelating [N,O] surface ligand was found to be more active than B, linked to the chelating [N,N] surface ligand. Moreover, the dihydride zirconium complexes are also more active than their corresponding monohydrides C–F. The C–C cleavage step occurs preferentially via β-alkyl transfer, which is the rate-limiting step in the alkane hydrogenolysis. The energetics of the comparative pathways over the potential energy surface diagram (PES) reveals the hydrogenolysis of n-butane into propane and ethane.

SHAPE EVOLUTION WITH SPIN IN 158Er AND 162Hf NUCLEI

The nuclear potential energies of neutron deficient even–even rare earth nuclei 158 Er and 162 Hf for the spin range 0–60 are computed within the framework of cranked Nilsson–Strutinsky shell correction method. The potential energy surface diagrams are analyzed in terms of quadrupole deformation and triaxiality parameter. The shape evolution of these isotopes with respect to spin is studied. The spin dependence of nuclear equilibrium potential energy is also verified.

Equilibrium shapes and deformations of some rare earth nuclei in cranked Nilsson-Strutinsky shell correction approach

The nuclear potential energies of neutron-deficient even-even rare earth nuclei ^{150-160}Dy, ^{150-160}Er, ^{150-160}Yb, ^{158,162,166-176}Hf, ^{160,164-178}W, and ^{162,166,170-180}Os are computed within the framework of the cranked Nilsson--Strutinsky shell correction method. The ground state potential energy surface diagrams of these nuclei are analysed in terms of quadrupole deformation and the triaxiality parameter. The nuclear shapes and deformations in the ground state are found to be functions of Z and N. Even though most of the isotopes in this region seem to be prolate in the ground state, oblate and triaxial shapes are also predicted for some isotopes. It is also found that the rare earth nuclei provide a platform for the study of phenomena such as nuclear shape changes and shape coexistence.

Femtosecond Kinetics of Photoconversion of the Higher Plant Photoreceptor Phytochrome Carrying Native and Modified Chromophores

The photoprocesses of native (phyA of oat), and of C-terminally truncated recombinant phytochromes, assembled instead of the native phytochromobilin with phycocyanobilin (PCB-65 kDa-phy) and iso-phycocyanobilin (iso-PCB-65 kDa-phy) chromophores, have been studied by femtosecond transient absorption spectroscopy in both their red absorbing phytochrome (P r) and far-red absorbing phytochrome (P fr) forms. Native P r phytochrome shows an excitation wavelength dependence of the kinetics with three main picosecond components. The formation kinetics of the first ground-state intermediate I 700, absorbing at ∼690 nm, is mainly described by 28 ps or 40 ps components in native and PCB phytochrome, respectively, whereas additional ∼15 and 50 ps components describe conformational dynamics and equilibria among different local minima on the excited-state hypersurface. No significant amount of I 700 formation can be observed on our timescale for iso-PCB phytochrome. We suggest that iso-PCB-65 kDa-phy either interacts with the protein differently leading to a more twisted and/or less protonated configuration, or undergoes P r to P fr isomerization primarily via a different configurational pathway, largely circumventing I 700 as an intermediate. The isomerization process is accompanied by strong coherent oscillations due to wavepacket motion on the excited-state surface for both phytochrome forms. The femto- to (sub-)nanosecond kinetics of the P fr forms is again quite similar for the native and the PCB phytochromes. After an ultrafast excited-state relaxation within ∼150 fs, the chromophores return to the first ground-state intermediate in 400–800 fs followed by two additional ground-state intermediates which are formed with 2–3 ps and ∼400 ps lifetimes. We call the first ground-state intermediate in native phytochrome I fr·750, due to its pronounced absorption at that wavelength. The other intermediates are termed I fr·675 and pseudo-P r. The absorption spectrum of the latter already closely resembles the absorption of the P r chromophore. PCB-65 kDa-phy shows a very similar kinetics, although many of the detailed spectral features in the transients seen in native phy are blurred, presumably due to wider inhomogeneous distribution of the chromophore conformation. Iso-PCB-65 kDa-phy shows similar features to the PCB-65 kDa-phy, with some additional blue-shift of the transient spectra of ∼10 nm. The sub-200 fs component is, however, absent, and the picosecond lifetimes are somewhat longer than in 124 kDa phytochrome or in PCB-65 kDa-phy. We interpret the data within the framework of two- and three-dimensional potential energy surface diagrams for the photoisomerization processes and the ground-state intermediates involved in the two photoconversions.

A study of the isomerization and dissociation of formal [acetone–methanol]+· ion–molecule complexes

The energy barrier for the keto–enol isomerization of the isolated acetone ion to its distonic (enol) isomer lies above its lowest dissociation limit and so the spontaneous isomerization can never be observed. Keto–enol isomerizations can be catalyzed within appropriate ion–molecule complexes. The present study involved two systems, [(CH3)2C=O···H+···O(H)CH2·] (ion 1) and [(CH3)2C=O···H+····OCH3] (ion 2), in both stable and metastable adducts. When acetone is bound to ·CH2OH though a proton bridge, shown as ion 1, an enol acetone ion is produced. This reaction results from a proton attaching to the acetone, which then gives an H· atom back to the radical site by a 1,6-H transfer, involving a transition state of low energy requirement. In contrast, when the acetone is protonated and bound to the radical CH3O· (ion 2), the above rearrangement does not take place. The metastable complex ion 2 loses a methyl radical, producing a new [C3H7O2]+ isomer of structure [CH3C+(O)···(H)OCH3]. Tandem mass spectrometry combined with ab initio calculations were used to investigate the two systems. Potential energy surface diagrams were obtained by calculations at the MP2/6-31+G(d) level of theory to aid further elucidation of the reaction mechanisms. Key words: ion–molecule complexes, keto–enol mechanisms, ion rearrangements and structures.

Exploring the potential energy surface of ion–molecule pairs by experiment and by theory: acetaldehyde and methanol

The energy barrier for the keto–enol isomerization of the isolated acetaldehyde ion to vinyl alcohol lies above its lowest dissociation limit and so the spontaneous isomerization is never observed. However, it has been shown that the distonic methanol ion can ionize the acetaldehyde molecule and greatly lower the energy barrier of the keto–enol isomerization. The present study involved two systems in which the acetaldehyde was associated with the distonic methanol cation, CH 2OH 2 +, and with its conventional isomer, CH 3OH + , in stable and metastable adducts. The isomerization barrier for acetaldehyde was lowered by association with CH 2OH 2 +; in contrast, the CH 3OH + ion did not facilitate the rearrangement of acetaldehyde to its enol ion. Tandem mass spectrometry combined with ab initio calculations was applied to investigate the two systems. Potential energy surface diagrams were obtained by MP2/6-31+g(d) and B3-LYP/6-31+g(d) calculations to further elucidate the reaction mechanisms.

Reactions of gaseous halocarbonyl cations with aromatic compounds: ionic carbonylation of inert CH bonds

The mass-selected halocarbonyl cations FCO +, ClCO +, and BrCO + were reacted with benzene, thiophene, pyrrole, and furan and a few of their alkyl derivatives to evaluate the ability of XCO + ions to promote CH bond activation of aromatic compounds (MH) via gas-phase ionic carbonylation. This novel reaction occurs via electrophilic addition followed by prompt HX elimination, forms the respective acylium ions (MCO +), and competes with electron abstraction and X + transfer. The intrinsic gas-phase reactivity order observed for ionic carbonylation was: FCO +>ClCO +>BrCO +. The ability of the fluorosulfinyl cation (FSO +) to promote analogous ionic sulfonylation of aromatic compounds was also tested, but owing to its high recombination energy, FSO + acts as a potent oxidizing agent and electron abstraction dominates. A novel, highly efficient and nearly exclusive O-abstraction reaction of FC + and SF + with N 2O was used to the straightforward preparation of gaseous FCO + and SFO +. B3LYP/6-311G++(d,p) potential energy surface diagrams were elaborate to help rationalize the observed reactivity trends.

Structure and Reactivity Studies of CoHNO+ in the Gas Phase

The structure and energetics of three CoHNO+ isomers [HCo(NO)+ (1), Co(HNO)+ (2), Co(NOH)+ (3)] were probed by using density functional theory (DFT). Theory predicts that 2 is the most stable structure with 1 and 3 14.1 and 15.4 kcal/mol less stable. We were unable to locate the transition states for 2 → 1 and 2 → 3 conversions. DFT calculations predict D°(CoH+−NO) = 34.6 kcal/mol and D°(Co+−HNO) = 45.5 kcal/mol. The gas-phase ion chemistry of CoHNO+ was also studied by using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry. CID and SORI−CID of CoHNO+ yield competitive formation of Co+, CoH+, and CoNO+. These results suggest that the barrier for 2 → 1 conversion is less than 45.5 kcal/mol. Reactions with simple molecules were dominated by NO and HNO displacements. Potential energy surface diagrams are presented to explain these displacement reactions. Surprisingly, CoHNO+ reacts with methane by dehydrogenation to yield CoCH3NO+. Studies suggest CH3CoNO+ rather than Co(CH3NO)+ as the structure for this ion.

Novel [3 + 2] 1,3-Cycloaddition of the Ionized Carbonyl Ylide +CH2OCH2• with Carbonyl Compounds in the Gas Phase

For the first time [3 + 2] 1,3-cycloaddition of an ionized carbonyl ylide has been observed in gas phase ion−molecule reactions of +CH2OCH2• (1) with several carbonyl compounds. The reaction, which competes with electrophilic addition that leads to net CH2•+ transfer, occurs across the CO double bond of acetaldehyde and several acyclic ketones yielding ionized 4,4-dialkyl-1,3-dioxolanes as unstable cycloadducts. Rapid dissociation of the nascent cycloadducts by loss of a 4-alkyl substituent as a radical leads to the observed products, that is cyclic 4-alkyl-1,3-dioxolanylium ions. Cycloaddition of 1 with cyclic ketones yields bicyclic spiro adducts, which also undergo rapid dissociation. Cyclobutanone yields ionized 1,3-dioxaspiro[4,3]octane, which dissociates exclusively by neutral ethene loss to ionized 4-methylene-1,3-dioxolane. Ionized 1,3-dioxaspiro[4,4]nonane is formed in reactions with cyclopentanone, and its rapid dissociation by loss of C3H6 and C2H5• yields the ionized 4-methylene-1,3-dioxolanylium and the 4-ethenyl-1,3-dioxolanylium product ions, respectively. A systematic study of this novel reaction and characterization of the product ions carried out via pentaquadrupole (QqQqQ) multiple stage (MS2 and MS3) mass spectrometric experiments provide experimental evidence for the cycloaddition mechanism. The dissociation chemistry observed for the cycloaddition products correlate well with their proposed structures and was compared to that of both isomeric and reference ions. Ab initio MP2/6-31G(d,p)//HF/6-31G(d,p) + ZPE potential energy surface diagrams for the reactions of 1 with acetone, fluoroacetone, and 1,1,1-trifluoroacetone support the operation of the two competitive reaction pathways, that is CH2•+ transfer and [3 + 2] 1,3-cycloaddition/dissociation, and show that the cycloaddition process is favored by electron-withdrawing substituents.

The generation, stability, dissociation and ion/molecule chemistry of sulfinyl cations in the gas phase

Sulfinyl cations [R–S+O (R = CH3, Ph, Cl, CH3O and C2H5O)] have been demonstrated by MO calculations in conjunction with pentaquadrupole multidimensional (2D and 3D) MS2 and MS3 mass spectrometric experiments to be stable and easily accessible gas phase species, and their dissociation and ion/molecule chemistry have been studied. Potential energy surface diagrams indicate that the sulfoxides (CH3)2SO, Ph2SO, Cl2SO, (CH3O)2SO and (C2H5O)2SO do not undergo rearrangement upon dissociative ionization, yielding the corresponding sulfinyl cations as primary fragments. Ph(CH3)SO+˙, on the other hand, is predicted to isomerize to CH3–S–O–Ph+˙via a four-membered ring transition state, yielding upon further CH3˙ loss the isomeric ion SO+–Ph. The sulfinyl cations were found by ab initio calculations to be much more stable than their SO+–R isomers, hence isomerization via[1,2-R] shifts is not expected. Direct cleavage of the R–SO+ bonds and/or processes that are preceded by isomerization dominate the low-energy collision dissociation chemistry of the sulfinyl cations, thus providing limited structural information. On the other hand, a general and structurally diagnostic ion/molecule reaction with 2-methyl-1,3-dioxolane occurs for all the sulfinyl cations yielding abundant net oxirane (C2H4O) addition products. The reaction probably occurs via a transketalization-like mechanism that leads to cyclic 2-thia-1,3-dioxolanylium ions. This reactivity parallels that of several acylium (R–C+O) and thioacylium ions (R–C+S), and is not shared by the isomeric ions SO+–Ph and CH2S+–OH. While the corresponding acylium ions react extensively with isoprene by [4 + 2+] cycloaddition, only the phenylsulfinyl cation Ph–S+O yields an abundant cycloadduct.

The isomers of ionized dimethyl sulfoxide (C2H6OS+·) and their CH3OS+ fragments. An ab initio and multiple‐stage mass spectrometric (MSn) study

AbstractThe relative stabilities, isomerizations and dissociations of ionized dimethyl sulfoxide (DMSO), its three C2H6OS+· isomers and of all their 14 conceivable CH3OS+ fragments (1–14), have been investigated by ab initio calculations at the MP2/6–31G(d,p)//6–31G(d,p) + ZPE and G2 levels of theory, and by multiple‐stage two‐ and three‐dimensional mass spectrometry performed in a pentaquadrupole instrument. The ab initio relative energies of the isomers, their connecting transition states, and their dissociation thresholds were used to elaborate potential energy surface diagrams that precisely corroborate and unify several previously divergent experimental observations on these systems. The most kinetically favorable isomerization of (CH3)2SO+· (I) to its aci‐form CH2S(OH)CH (II) displays a transition state considerably lower in energy than the threshold for its direct dissociation by CH3⋅ loss. Therefore, low‐energy, long‐lived metastable ions I are predicted to isomerize to II, and to dissociate in turn to CH2S+OH (2) upon CH3⋅ loss. Ions I excited a few electronvolts above the threshold are, on the other hand, predicted to dissociate directly to CH3S+O (1). Isomerization of I to the most stable C2H6OS+· ion, that is CH3SOCH (III), displays the most energetic transition state and should be negligible, whereas III is predicted to dissociate by CH3⋅ loss preferentially to 1 rather than 5 (CH3OS+). Nine CH3OS+ isomers, that is 1, 2, (HCS…OH2)+ (3), +CH2S(O)H (4), 5, HC(SH)OH+ (9), CH2OSH+ (10), CH2+OSH (11), and (HCO…SH2)+ (14), were found as true minima on the RHF/6–31G(d,p) potential‐energy surface, and some of their isomerization barriers and dissociation thresholds were estimated. Tandem and multiple‐stage (MS3) mass spectrometric experiments show that non‐dissociating DMSO+· ions produce, upon collision‐induced dissociation (CID), a mixture of approximately 40% of 1 and 60% of 2, whereas the CID chemistry of 1 and 2 is affected considerably by the collision energies employed. Both the experimental and theoretical results on 1 and 2 allow a detailed interpretation of their complex dissociation chemistry, which clarifies the nature of most of their indirect fragments. Such fragments are proposed to be formed via the common isomerization/dissociation sequences 1 → 2 → 9 ⇌ 3 → HCS+ (m/z 45) + H2O, and 1 → 2 → [7, HOCH2S+] → S + CH2OH+ (m/z 31). These processes are favored at lower collision energies, whereas direct dissociation of 1 to CH3+ (m/z 15) and SO+· (m/z 48), and of 2 to CH2S+· (m/z 46) occurs to greater extents at higher collision energies.

Bimolecular nucleophilic substitution (SN2) reactions of neopentyl arenesulfonates with anilines and benzylamines in methanol

Bimolecular nucleophilic substitution (SN2) reactions of neopentyl arenesulfonates with anilines and benzylamines in methanol at 55.0 °C are reported. The tightness of the transition state (TS) is similar to that for other typical SN2 processes at a primary alkyl carbon centre based on the magnitude of the cross-interaction constant ρxz(0.30) between the substituents in the nucleophile (X) and leaving group (Z). The TS variation is in accord with that predicted by the potential energy surface diagram, which in turn is consistent with the positive sign of ρxz; a later TS is obtained with a weaker nucleophile and nucleofuge. Taft's polar substituent constant, σ*, for the trimethylsilyl group is estimated to be –0.48 by using a factor of 1.875 for the fall-off of σ* from the tert-butyl to the neopentyl group and extrapolating from the experimental Taft plot.

Nucleophilic substitution reactions of allyl arenesulphonates with anilines and N,N-dimethylanilines

Kinetic studies of the reactions of allyl arenesulphonates, I, with anilines and N,N-dimethylanilines in acetonitrile at 45.0 °C are reported. The sign and magnitude of the cross-interaction constants ρxz(andβxz) between substituents in the nucleophile (X) and leaving group (Z) indicate that the transition state (TS) for I is relatively tight and is similar to that for the corresponding reactions of ethyl systems, rather than for benzyl systems. Variations of the simple Hammett (and Bronsted) coefficients ρx(βx) and ρx(βx) with substituents Z and X, respectively, are consistent with the trend expected from a positive ρxzi.e., that predicted by the potential energy surface diagram. The kinetic isotope effects involving N-deuteriated anilines support the mechanism proposed based onρxz(βxz) for the reactions of I, i.e., an associative SN2 process with an earlier TS for a stronger nucleophile and/or a better leaving group.

The effect of the nature of the amine leaving group on the nature of the E2 transition state for the reaction of 1-phenylethylammonium ions with sodium ethoxide in ethanol

To investigate the effect of the leaving group on the elimination reaction of 1-phenylethylammonium ions with sodium ethoxide in ethanol at 60 °C, the reaction of seven different quaternary ammonium salts and their β-deuterated analogues with trimethylamine, N-methylpiperidine, N-methyldiethylamine, triethylamine, N,N-dimethylbenzylamine, tripropylamine, and N,N-diethylbenzylamine as leaving groups has been studied. In all cases the elimination, which was shown to proceed via the concerted E2 process, was accompanied by competing substitution reactions. Although a significant dependence of the rate of the elimination process on the nature of the leaving group was noted, there was not any linear correlation with the basicity of the amine leaving group. The primary hydrogen–deuterium kinetic isotope effect for the elimination process, (kH/kD)E, was found to increase initially with an increase of reaction rate, [Formula: see text] for substrates containing the leaving groups trimethylamine, N-methylpiperidine, N-methyldiethylamine, triethylamine, and N,N-dimethylbenzylamine; i.e., (kH/kD)E = 5.03, 5.26, 5.40, 5.83, and 5.85, respectively. A further increase in rate, using substrates with tripropylamine and N,N-diethylbenzylamine as leaving groups resulted in a decrease of the magnitude of the hydrogen–deuterium isotope effect; i. e., (kH/kD)E = 5.42 and 4.67, respectively. It is concluded that steric effects mainly determine leaving group ability. As well, it is concluded that the leaving group ability of the amine determines the structure of the E2 transition state. For the reaction of the poorer leaving groups, trimethylamine, N-methylpiperidine, and N-methyldiethylamine, the proton is morethan one-half transferred at the transition state while for reaction involving the two best leaving groups, tripropylamine and N,N-diethylbenzylamine, the Cβ—H bond is lessthan one-half broken at the transition state. The conclusions are considered in the light of the More O'Ferrall – Jencks potential energy surface diagram. Keywords: elimination mechanism, transition state, isotope effects, leaving group, quaternary salts.

Relationships between geometries and energies of identity SN2 transition states: the dominant role of the distortion energy and its origin

At the 4-31G computational level, the intrinsic barriers of eight identity SN2 reactions X− + CH3X → XCH3 + X− are less than the energies required to distort CH3X from its ground state geometry to its transition state geometry by a constant 25 kcal/mol. The distortion energy and its C—X stretching and H—C—X bending components can be calculated directly, or, alternatively, estimated from the force constants and bond dissociation energies of CH3X. Regardless of the mode of computation, the distortion energies are found to be dominated by the C—X stretching deformations, and these are linearly correlated with the intrinsic barriers. The total deformation energies are also linearly correlated with the intrinsic barriers. The transition vectors of the eight identity reactions have been calculated; each is dominated by the C—X stretch. The percentage of C—X stretching at the transition state, here termed the Distortion Index (DI), reflects the "tightness" or "looseness" of this structure. The intrinsic barrier increases as the DI increases, i.e., as the transition state becomes more "exploded". This result does not agree with the predictions of a More O'Ferrall–Jencks potential energy surface diagram. However, as shown in some detail, all of the computational results of the present work are in harmony with the surface crossing diagram model of the barrier. The essential feature of this model is the notion that the activation process in an identity SN2 reaction is a result of the distortion that is required to transfer one electron from X− to CH3X.