Effect of substituents on the strength of N-X (X = H, F, and Cl) bond dissociation energies: a high-level quantum chemical study

The effect of substituents on the strength of N-X (X = H, F, and Cl) bonds has been investigated using the high-level W2w thermochemical protocol. The substituents have been selected to be representative of the key functional groups that are likely to be of biological, synthetic, or industrial importance for these systems. We interpreted the effects through the calculation of relative N-X bond dissociation energies (BDE) or radical stabilization energies (RSE(NX)). The BDE and RSE(NX) values depend on stabilizing/destabilizing effects in both the reactant molecule and the product radical of the dissociation reactions. To assist us in the analysis of the substituent effects, a number of additional thermochemical quantities have been introduced, including molecule stabilization energies (MSE(NX)). We find that the RSE(NH) values are (a) increased by electron-donating alkyl substituents or the vinyl substituent, (b) increased in imines, and (c) decreased by electron-withdrawing substituents such as CF(3) and carbonyl moieties or through protonation. A different picture emerges when considering the RSE(NF) and RSE(NCl) values because of the electronegativities of the halogen atoms. The RSE(NX)s differ from the RSE(NH) values by an amount related to the stabilization of the N-halogenated molecules and given by MSE(NX). We find that substituents that stabilize/destabilize the radicals also tend to stabilize/destabilize the N-halogenated molecules. As a result, N-F- and N-Cl-containing molecules that include alkyl substituents or correspond to imines are generally associated with RSE(NF) and RSE(NCl) values that are less positive or more negative than the corresponding RSE(NH). In contrast, N-F- and N-Cl-containing molecules that include electron-withdrawing substituents or are protonated are generally associated with RSE(NF) and RSE(NCl) values that are more positive or less negative than the corresponding RSE(NH).     

The radical stabilization energy of a substituted carbon-centered free radical depends on both the functionality of the substituent and the ordinality of the radical

Chemical intuition suggests that the stabilization of a carbon-centered free radical by a substituent X would be the greatest for a prim and least for a more stable tert radical because of "saturation". However, analysis of a comprehensive recent set of bond dissociation energies computed by Coote and co-workers (Phys. Chem. Chem. Phys. 2010, 12, 9597) and transformed into radical stabilization energies (RSE) suggests that this supposition is often violated. The RSE for a given X depends not only on the nature of X but also on the ordinality (i.e., prim, sec, or tert) of the radical onto which it is substituted. For substituents that stabilize by electron delocalization but also contain electron-withdrawing centers, such as the carbonyl function, the stabilization of XCMe(2)(?) compared with HCMe(2)? is greater than that for XCH(2)? compared with HCH(2)?. However, for substituents that stabilize by lone-pair electron donation, such as N or O centers, the order is strongly reversed. This contrast can be qualitatively rationalized by considering charge-separated VB contributors to the radical structure (R(2)C(+)-X(-?) and R(2)C(-)-X(+?)) and the contrasting effects of methyl substituents on them. This conclusion is not dependent on the particular definition used for RSE.     

Effects of substituents on the stability of phosphoranyl radicals

The effect of substituents on the geometries, apicophilicities, radical stabilization energies, and bond dissociation energies of (*)P(CH(3))(3)X (X = CH(3), SCH(3), OCH(3), OH, CN, CF(3), Ph) were studied via high-level ab initio molecular orbital calculations. Two alternative definitions for the radical stabilization energy (RSE) were considered: the standard RSE, in which radical stability is measured relative to H-P(CH(3))(3)X, and a new definition, the alpha-RSE, which measures stability relative to P(CH(3))(2)X. We show that these alternative definitions yield almost diametrically opposed trends; we argue that alpha-RSE provides a reasonable qualitative measure of relative radical stability, while the standard RSE qualitatively reflects the relative strength of the P-H bonds in the corresponding H-P(CH(3))(3)X phosphines. The (*)P(CH(3))(3)X radicals assume a trigonal-bipyramidal structure, with the X-group occupying an axial position, and the unpaired electron distributed between a 3p(sigma)-type orbital (that occupies the position of the "fifth ligand"), and the sigma orbitals of the axial bonds. Consistent with this picture, the radical is stabilized by resonance (along the axial bonds) with configurations such as X(-) P(*+)(CH(3))(3) and X(*) P(CH(3))(3). As a result, substituents that are strong sigma-acceptors (such as F, OH, or OCH(3)) or have weak P-X bonds (such as SCH(3)) stabilize these configurations, resulting in the largest apicophilicities and alpha-RSEs. Unsaturated pi-acceptor substituents (such as phenyl or CN) are weakly stabilizing and interact with the 3p(sigma)-type orbital via a through-space effect. As part of this work, we challenge the notion that phosphorus-centered radicals are more stable than carbon-centered radicals.     

Composite Correlated Molecular Orbital Theory Calculations of Ring Strain for Use in Predicting Polymerization Reactions

Strained ring systems play an important role in synthesis and can be characterized by the ring strain energy (RSE). The RSE of 3, 4, 5, and 6 membered saturated and unsaturated ring systems containing N, O, P, and S heteroatoms and H, F, SiMe₃, and SO₂Me substituents were calculated at the G3(MP2) composite correlated molecular orbital theory level using up to 5 models to predict the RSE. Generally, the RSE decreased as ring size increased with a substantial decrease from 4 to 5 membered rings. Replacement of a ring CH₂ with P or S reduced the RSE, consistent with less angle strain. The RSE for unsaturated systems were generally greater than for saturated systems due to increased angle strain. No general trends were found with respect to substituent effects. The RSE values suggest that 3-pyrroline and 2-pyrroline and their derivatives may be able to support ring opening metathesis polymerization and warrant further study.     

Engineering Reactions in Crystalline Solids: Radical Pairs in Crystals of Dialkyl 1,3-Acetonedicarboxylates

Crystalline dialkyl 1,3-acetonedicarboxylates give dialkyl succinates in high chemical yields by combination of alpha-carbonyl radical pairs produced by photochemical decarbonylation. It is proposed that the solid-state reaction depends on the exothermicity of two consecutive bond cleavage processes. It is also suggested that the efficiency of radical formation in the solid state is determined by the effect of substituents on bond dissociation energies and radical-stabilization abilities.     

Borane–Lewis Base Complexes as Homolytic Hydrogen Atom Donors

Radical stabilization energies (RSE)s have been calculated for a variety of boryl radicals complexed to Lewis bases at the G3(MP2)‐RAD level of theory. These are referenced to the B? H bond dissociation energy (BDE) in BH₃ determined at W4.3 level. High RSE values (and thus low BDE(B? H) values) have been found for borane complexes of a variety of five‐ and six‐membered ring heterocycles. Variations of RSE values have been correlated with the strength of Lewis acid–Lewis base complex formation at the boryl radical stage. The analysis of charge‐ and spin‐density distributions shows that spin delocalization in the boryl radical complexes constitutes one of the mechanisms of radical stabilization.     

Remote substituent effects on allylic and benzylic bond dissociation energies. Effects on stabilization of parent molecules and radicals

The effect of remote substituents on bond dissociation energies (BDE) is examined by investigating allylic C-F and C-H BDE, as influenced by Y substituents in trans-YCH=CHCH2-F and trans-YCH=CHCH2-H. Theoretical calculations at the full G3 level model chemistry are reported. The interplay of stabilization energies of the parent molecules (MSE) and of the radicals formed by homolytic bond cleavage (RSE) and their effect on BDE are established. MSE values of allyl fluorides yield an excellent linear free energy relationship with the electron-donating or -withdrawing ability of Y and decrease by 4.2 kcal mol-1 from Y = (CH3)2N to O2N. RSE values do not follow a consistent pattern and are of the order of 1-2 kcal mol-1. A decrease of 4.1 kcal mol-1 is found in BDE[C-F] from Y = CH3O to NC. BDE[YCH=CHCH2-H] generally increases with decreasing electron-donating ability of Y for electron-donating groups and does not follow a consistent pattern with electron-withdrawing groups, the largest change being an increase of 3.6 kcal mol-1 from Y = (CH3)2N to CF3. The G3 results are an indicator of benzylic BDE in p-YC6H4CH2-F and p-YC6H4CH2-H, via the principle of vinylogy, demonstrated by correlating MSE of the allylic compounds with physical properties of their benzylic analogues.     

Theoretical studies on the mechanism of the thermal decarboxylation and decarbonylation of a number of α-keto-acids

Both processes of decarboxylation and decarbonylation of a number of acids including RCOCO2H,R=H,CH3,CH2F,CF3,CH=CH2,Ph,OH have been studied by semi-empirical MO theory AMI method to verify the reaction mechanism of each process and the effect of different substituents on them.The calculated results are consistent with the experimental reports and can be summed up as follows:(1) The decarboxylation of these acids to form aldehydes and carbon dioxide is concerted and takes place through a 4-membered ring transition state in which a partial negative charge develops on the carbon of the α-carbonyl group,so that the inductive effect of some substituents is favourable for this process.(2) Their decarbonylation into carboxylic acids and carbon monoxide however is the attack of the OH on the carbon of the alkyl portion of the acid,forming a 3-membered ring transition state.(3) The activation energy of decarbonylation is lower than that of decarboxylation,since oxygen is more nucleophilic than hydrogen and als     

The Driving Force for the Acylation of β-Lactam Antibiotics by L,D-Transpeptidase 2: Quantum Mechanics/Molecular Mechanics (QM/MM) Study

β-lactam antibiotics, which are used to treat infectious diseases, are currently the most widely used class of antibiotics. This study focused on the chemical reactivity of five- and six-membered ring systems attached to the β-lactam ring. The ring strain energy (RSE), force constant (FC) of amide (C−N), acylation transition states and second-order perturbation stabilization energies of 13 basic structural units of β-lactam derivatives were computed using the M06-2X and G3/B3LYP multistep method. In the ring strain calculations, an isodesmic reaction scheme was used to obtain the total energies. RSE is relatively greater in the five-(1a–2c) compared to the six-membered ring systems except for 4b, which gives a RSE that is comparable to five-membered ring lactams. These variations were also observed in the calculated inter-atomic amide bond distances (C−N), which is why the six-membered ring lactams C−N bond are more rigid than those with five-membered ring lactams. The calculated ΔG^# values from the acylation reaction of the lactams (involving the S−H group of the cysteine active residue from L,D transpeptidase 2) revealed a faster rate of C−N cleavage in the five-membered ring lactams especially in the 1–2 derivatives (17.58 kcal mol⁻¹). This observation is also reflected in the calculated amide bond force constant (1.26 mDyn/A) indicating a weaker bond strength, suggesting that electronic factors (electron delocalization) play more of a role on reactivity of the β-lactam ring, than ring strain.     

Substituent effects and the role of negative hyperconjugation in siloxycarbene rearrangements

Substituent effects and the role of negative hyperconjugation in 1,2-silyl migration and decarbonylation of methoxy(substituted-siloxy)carbenes have been investigated using quantum chemical calculations and natural bond orbital analysis. It has been found that sigma-electron-withdrawing substituents generally lower the barriers for 1,2-silyl migration and decarbonylation, consistent with symmetry-forbidden concerted rearrangements involving intramolecular front-side nucleophilic attack by the carbene lone pair at silicon and by the methoxy oxygen at silicon, respectively. However, while good linear Hammett correlations are obtained for 1,2-silyl migration, those obtained for decarbonylation are poor. In addition, there appears to be a relationship between the extent of pertinent hyperconjugative interactions in the siloxycarbene conformers and the ease of intramolecular reactivity. As a matter of fact, the finding that 1,2-silyl migration is more favorable than decarbonylation seems to be primarily related to stronger negative hyperconjugation between the carbene lone pair and the O-Si antibonding orbital, compared to that between the methoxy oxygen n(sigma) lone pair and the O-Si antibonding orbital. Moreover, the activation enthalpies for 1,2-silyl migration decrease linearly with stronger negative hyperconjugation, although no such correlation could be established for decarbonylation.     

Factors influencing the C?ON bond strength of the alkoxyamines in the styrene–acrylonitrile–TEMPO copolymerization system

Homolytic bond dissociation energy (BDE) of the (C? ON) bond for several N‐alkoxyamines derived from 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) and the corresponding (C? H) bonds were determined from quantum‐mechanical calculations including the B3‐LYP6‐31G(d), B3‐LYP/6‐311++G(2df,p), UB3‐LYP/6‐311+G(3df,2p), and integrated IMOMO (G3:ROMP2/6‐31G(d)) method. The investigated N‐alkoxyamines were considered as models for dormant forms of propagating chains in the radical copolymerization process of styrene with acrylonitrile in the presence of TEMPO according to the terminal and penultimate model. The substituent effect on BDE was investigated. Radical stabilization energies (RSE) for radicals created from homolysis of the investigated N‐alkoxyamines were calculated according to Rüchardt's method. Polar, steric, and stabilization effects on C? ON alkoxyamine bond homolysis were studied. A dramatically weakened C? ON bond in the alkoxyamine‐containing two consecutive styrene units in the propagating chain was ascribed to geometric parameters characterizing energetically unfavorable conformation of the substituents. These phenomena can be regarded as the penultimate effect in the radical living/controlled copolymerization system of styrene with acrylonitrile. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1165–1177, 2008     

A relative approach for determining ring strain energies of heterobicyclic alkenes

Ring strain energies (RSEs) of heterocyclic compounds are predicted compared to their analogous homocyclic compounds using the G3 method. Suitable reference compounds are devised for row 2 and row 3 heterobicyclic alkenes. Any difference in energy between the ring and the reference is due to RSE. Row 3 heterobicyclic alkene RSEs are less than those of row 2. As the electronegativity of the heteroatom increases, the RSE increases. Substitutents at the bridgehead carbons cause a decrease in RSE. [3.2.1] Heterobicyclic alkenes are significantly less strained than their [2.2.1] counterparts. Relative and absolute RSEs are reported for heterobicyclic alkenes and their derivatives.     

Synthesis and characterization of 3-aryl-2-(polystyryl)cyclopropenones via cyclopropenium ion substitution on polystyrene

Electrophilic substitution of cyclopropenium ions on aromatic polymers offers a unique opportunity to introduce polar functionality in a controlled manner to conventional, nonpolar polymers. Phenylcyclopropenone substituted polystyrene with predictable chemical composition and narrow molecular weight distribution were prepared. Size exclusion chromatography (SEC) analysis demonstrated the absence of branching or crosslinking in these functionalized polystyrenes during electrophilic substitution of the parent homopolymer. ¹³C-NMR confirmed that the degree of phenylcyclopropenone substitution was both highly efficient and predictable over a broad compositional range. The glass transition temperature (T_g) of the polymers was found to vary linearly with mole % phenylcyclopropenone substitution of the polystyrene. Thermal gravimetric analysis (TGA) indicated that thermal decarbonylation of the appended cyclopropenones occurred at approximately 180°C. Weight loss vs. temperature profiles correlated reasonably well with levels of substitution based on ¹³C-NMR analysis, confirming that decarbonylation of the calculated cyclopropenone substituents was the predominant thermal decomposition pathway. © 1995 John Wiley & Sons, Inc.     

Detailed kinetic study of the ring opening of cycloalkanes by CBS-QB3 calculations

This work reports a theoretical study of the gas-phase unimolecular decomposition of cyclobutane, cyclopentane and cyclohexane by means of quantum chemical calculations. A biradical mechanism has been envisaged for each cycloalkane, and the main routes for the decomposition of the biradicals formed have been investigated at the CBS-QB3 level of theory. Thermochemical data(DeltaHf(o), S(o), Cp(o)) for all the involved species have been obtained by means of isodesmic reactions. The contribution of hindered rotors has also been included. Activation barriers of each reaction have been analyzed to assess the energetically most favorable pathways for the decomposition of biradicals. Rate constants have been derived for all elementary reactions using transition-state theory at 1 atm and temperatures ranging from 600 to 2000 K. Global rate constant for the decomposition of the cyclic alkanes in molecular products have been calculated. Comparison between calculated and experimental results allowed us to validate the theoretical approach. An important result is that the rotational barriers between the conformers, which are usually neglected, are of importance in decomposition rate of the largest biradicals. Ring strain energies (RSE) in transition states for ring opening have been estimated and show that the main part of RSE contained in the cyclic reactants is removed upon the activation process.     

Substituent influences on the stability of the ring and chain tautomers in 1,3-O,N-heterocyclic systems: characterization by 13C NMR chemical shifts, PM3 charge densities, and isodesmic reactions

Substituent effects on the stabilities of the ring and chain forms in a tautomeric equilibrium of five series of 2-phenyloxazolidines or -perhydro-1,3-oxazines possessing nine different substitutions at the phenyl moiety have been studied with the aid of 13C NMR spectroscopy and PM3 charge density and energy calculations. Reaction energies of the isodesmic reactions, obtained from the calculated energies of formation, show that electron-donating substituents stabilize both the chain and ring tautomers but the effect is stronger on the stability of the chain form than on that of the ring form. The 13C chemical shift changes induced by the phenyl substituents (SCS) were analyzed by several different single and dual substituent parameter approaches. The best correlations were obtained by equation SCS = rhoFsigmaF + rhoRsigmaR. In all cases the rhoF values and in most cases also the rhoR values were negative at both the C=N and C-2 carbons, indicating a reverse behavior of the electron density. This concept could be verified by the charge density calculations. The 13C chemical shifts of the C=N and C-2 carbons show a normal dependence on the charge density (q(tot)), but the charge density shows a reverse dependence on substitution. Correlation analysis of the 13C chemical shifts, solvent effect (CDCl3 vs DMSO-d6) on the NMR behavior as well as the effect of substituents on the electron densities and on the stabilities of the ring and chain tautomers show that the substituent dependence of the relative stability of the ring and chain tautomers in equilibrium is governed by several different electronic effects. At least intramolecular hydrogen bonding between the imine nitrogen and the hydroxyl group as well as polarization of the C=N bond seem to contribute in the chain form. Stereoelectronic and electrostatic effects are possible to explain the increase in stability of the ring form by electron-donating substituents.     

Ring strain energies: substituted rings, norbornanes, norbornenes and norbornadienes

Ring strain energies (RSEs) are predicted using homodesmotic reactions at the B3LYP/6-31G^* level of theory. Substituents are conserved in the acyclic reference and any difference in energy between the ring and the acyclic reference corresponds exclusively to RSE. Small rings are stabilized by alkyl substituents and this stabilization decreases as the size of the ring increases. There is a destabilization of medium sized rings. Greater stabilization is found upon alkyl substitution at a double bond in an unsaturated ring and this stabilization decreases as ring size increases. The effects of cis-1,2-disubstitution on RSEs have been evaluated and indicate stabilization for both small and medium sized rings. RSEs of saturated and unsaturated polycyclic systems agree well with the RSEs derived from experimental thermochemical data. RSEs are reported for substituted norbornanes, norbornenes, and norbornadienes to complement experimental studies.     

Stability of phosphinidenes--are they synthetically accessible?

The relative stability of different singlet phosphinidenes (R-P) has been investigated by using isodesmic reactions. The energies of these reactions with several R groups were calculated with DFT and ab initio methods at different levels of theory. The best stabilising effect on the phosphinidene centre is exhibited by the R'2C=N-group, resulting in a singlet ground state. The analysis of the electron density in the parent H2C=N-P, indicates a considerable double bond character of the PN bond. Further tuning of the C=N pi-bond polarity is possible by variation of the R' substituents. Using trimethylsilyl substituents or incorporating the carbon atom in a pi-withdrawing pentafulvene ring the stabilization and the computed singlet triplet separation increases. The thermodynamics and the kinetics of dimerisation reactions of the most stabilised R'2C=N-P indicates that these compounds are likely synthetic targets.     

Excited states and electronic spectra of annulated dinuclear free-base phthalocyanines: a theoretical study on near-infrared-absorbing dyes

The electronic excited states and electronic absorption spectra of annulated dinuclear free-base phthalocyanine (C(58)H(30)N(16)) are studied through quantum chemical calculations using the symmetry-adapted cluster-configuration interaction (SAC-CI) method. Three tautomers are possible with respect to the position of the pyrrole protons; therefore, the SAC-CI calculations for these tautomers were performed. The structures of the Q-band states are discussed based on the character of their molecular orbitals. The lower energy shift of the Q-bands because of dimerization is explained by the decrease in the HOMO-LUMO gaps resulting from the bonding and antibonding interactions between the monomer units. The electronic dipole moments of the nonsymmetric tautomer were calculated, and the possibility of charge-separated excited states is discussed. The relative energies of these tautomers are examined using density functional theory (DFT) calculations for several peripheral substituents. The relative energies of these tautomers significantly depend on the substituents, and therefore, the abundance ratios of the three tautomers were affected by the substituents. The absorption spectra were simulated from the SAC-CI results weighted by the Boltzmann factors obtained from the DFT calculations. The SAC-CI spectra reproduce the experimental findings well. The thermal-averaged SAC-CI spectra could explain the observed substituent effect on the structure of the Q-bands in terms of the relative stabilities and the abundance ratios of the tautomers. The SAC-CI and time-dependent density functional theory calculations are also compared. The CAM-B3LYP results agreed with the trends of the SAC-CI results; however, the CAM-B3LYP calculation overestimated the excitation energies in comparison with the SAC-CI and experimental results.     

Substituent Effects on the C-H Bond Dissociation Energy of Toluene. A Density Functional Study

The bond dissociation energies of the benzylic C-H bond of a series of 16 para-substituted toluene compounds (p-X-C(6)H(4)CH(3)) have been calculated with the density functional method (BLYP/6-31G). The calculated substituent effects correlate well with experimental rates of dimerization of para-substituted alpha,beta,beta-trifluorostyrenes and rearrangement of methylenearylcyclopropanes. Both electron-donating and electron-withdrawing groups reduce the bond dissociation energy (BDE) of the benzylic C-H bond because both groups cause spin delocalization from the benzylic radical center. The calculated spin density variations at the benzylic radical centers correlate well with both the ESR hyperfine coupling constants determined by Arnold et al. and the calculated radical effects of the substituents. The relative radical stabilities are mainly determined by the spin delocalization effect of the substituents, and polar effect of the substituents are not important in the current situation. The ground state effect is also found to influence the C-H BDE.