Substituent effect and multisite protonation in the fragmentation of alkyl benzoates

The dissociation of protonated alkyl benzoates (para H, CN, OMe and NO(2)) into protonated benzoic acids and alkyl cations was studied in the gas phase. It was found that the product ratio depends on the substituent at the para position of the phenyl ring. The substituent effect is probably the result of the formation of an ion-neutral complex intermediate that decomposes to an ion and a neutral, according to the relative proton affinities of the two moieties. The experimental results and theoretical calculations indicate that the favored protonation site in these compounds is the ester's carbonyl and that proton transfer from the phenyl ring to the ester group is very likely to occur under chemical ionization conditions. It is most probable that the carbonyl protonated form is a common intermediate in the fragmentation process, regardless of the protonation site.     

Reactivity indices as a measure of rate constants for protonation of radical anions and dianions

The DFT-based reactivity indices were used to describe protonation reactions of radical anions (RA) and dianions (DA) of aromatic compounds. A correlation between the experimental rate constants for protonation and the global reactivity indices was found. The indices were expressed through the electron affinities and ionization energies computed at the B3LYP level of theory. The protonation reactions of RA and DA of aromatic compounds are correctly described by the reactivity indices calculated as the inverse of the difference between the formal formation potential of RA (or DA) and the formal reduction potential of the proton donor.     

The Protonated Guanine–Cytosine Base Pair

Protonated base pairs were recently implicated in the context of DNA proton transfer and charge migration. The effects of protonating different sites of the guanine–cytosine (GC) base pair are studied here by using the DZP++ B3LYP density functional method. Optimized structures for the protonated GC base pair are compared with those of parent GC and the neutral hydrogenated GC radical (GCH). Proton and hydrogen‐atom additions significantly disturb the structure of the GC base pair. However, the structural perturbations arising from protonation are often less than those arising from hydrogenation of GC. Protonation of the GC base pair causes significant strengthening of the interstrand hydrogen bonds and a concomitant increase in the base dissociation energies. The adiabatic ionization potentials (AIPs), vertical ionization potentials (VIPs), and proton affinities (PAs) for the different protonation sites of the GC base pair are predicted. The N7 site of guanine is the preferred site for protonation of the GC base pair.     

Reactivity and core-ionization energies in conjugated dienes. Carbon 1s photoelectron spectroscopy of 1,3-pentadiene

The high-resolution carbon 1s photoelectron spectrum of trans-1,3-pentadiene has been resolved into contributions from the five inequivalent carbon atoms, and carbon 1s ionization energies have been assigned to each of these atoms. Spectra have also been measured for propene and 1,3-butadiene at better resolution than has previously been available. The ionization energies for the sp2 carbons are found to correlate well with activation energies for electrophilic addition and with proton affinities. Comparing the results for 1,3-pentadiene with those for ethene, propene, and 1,3-butadiene as well as with results of theoretical calculations makes it is possible to assess the effect of the terminal methyl group in 1,3-pentadiene. As in propene, the methyl group contributes electrons to the beta carbon through the pi system. In addition, there is a significant (though smaller) contribution from the methyl group to the terminal (delta) CH2 carbon, also through the pi system. Most of the effect of the methyl group is present in the ground-state molecule. There are only relatively small contributions from the methyl group to the ionization energies from redistribution of charge in the pi system in response to the removal of a core electron. In addition to these specific effects, there is an overall decrease in average ionization energy as the size of the molecule increases as well as effects that are specific to the conjugated systems in 1,3-butadiene and 1,3-pentadiene. The results provide insight into the reactivity and regioselectivity of conjugated dienes.     

Structural and energetic aspects of the protonation of phenol,catechol, resorcinol,and hydroquinone

The various protonated forms of phenol (1), catechol (2), resorcinol (3), and hydroquinone (4) were explored by ab initio quantum chemical calculations at the MP2/6-31G(d) and B3LYP/6-31G(d) levels. Proton affinities (PA) of 1-4 were calculated by the combined G2(MP2,SVP) method, and their gas-phase basicities were estimated after calculation of the change in entropy on protonation. These theoretical data were compared with the corresponding experimental values determined in a high-pressure mass spectrometer. This comparison confirmed that phenols are essentially carbon bases and that protonation generally occurs in a position para to the hydroxyl group. Resorcinol is the most effective base (PA = 856 kJ mol-1) due to the participation of both oxygen atoms in the stabilization of the protonated form. Since protonation is accompanied by a freezing of the two internal rotations, a significant decrease in entropy is observed. The basicity of catechol (PA = 823 kJ mol-1) is due to the existence of an intramolecular hydrogen bond, which is strengthened upon protonation. The lower basicity of hydroquinone (PA = 808 kJ mol-1) is a consequence of the fact that protonation necessarily occurs in a position ortho to the hydroxyl group. When the previously published data are reconsidered and a corrected protonation entropy is used, a proton affinity value of 820 kJ mol-1 is obtained for phenol.     

Doubly protonated benzene in the gas phase

Structural aspects and the unimolecular fragmentations of doubly protonated benzene are studied by means of tandem-mass spectrometry. The corresponding dications are generated by electron ionization (EI) of 1,3- and 1,4-cyclohexadienes, respectively. It is suggested that EI of 1,3-cyclohexadiene leads to the singlet state of doubly protonated benzene, whereas EI of 1,4-cyclohexadiene yields a mixture of singlet and triplet states. Unimolecular fragmentation of doubly protonated benzene exclusively proceeds via dehydrogenation leading to the benzene dication. The proton affinities (PAs) of protonated benzene amount to PA(C(6)H(7)(+))(meta) = 1.9 +/- 0.3 eV for protonation taking place at the meta-position, PA(C(6)H(7)(+))(ortho) = 1.5 +/- 0.2 eV, and PA(C(6)H(7)(+))(para) = 0.9 +/- 0.2 eV, respectively. Various facets of the experiments are compared with density functional theory calculations and generally good agreement is found.     

Complete basis set, the MP2 ab initio, and hybrid density functional theory evaluation of ionization potential and electron affinity for PH, PH2, PHF, PF, and PF2

A systematic study was performed on the small molecular systems built from phosphor, hydrogen and fluorine with the target being to evaluate accurately their ionization potentials and electron affinities, as well as influence fluorine on the ionization potential of phosphor as a central atom. To determine the accuracy of hybrid density functional methods for computing those energies, ionization energies for hydrogen, fluorine and phosphor were calculated and compared with the experimental and CBSQ values. To demonstrate the accuracy of this method, both the ionization potential and the electron affinity for phosphorus and fluorine atoms were calculated and compared with the experimental data. For both PF and PF₂, an identical electron affinity of 0.72 eV and for PH and PHF 1.0 eV were suggested.     

Dissociative protonation sites: reactive centers in protonated molecules leading to fragmentation in mass spectrometry

It is often found in mass spectrometry that when a molecule is protonated at the thermodynamically most favorable site, no fragmentation occurs, but a major reaction is observed when the proton migrates to a different position. For benzophenones, acetophenones, and dibenzyl ether, which are all preferentially protonated at the oxygen, deacylation or dealkylation was observed in the collision-induced dissociation of the protonated molecules. For para-monosubstituted benzophenones, electron-withdrawing substituents favor the formation of RC6H4CO+ (R = substituent), whereas electron-releasing groups favor the competing reaction leading to C6H5CO+. The ln[(RC6H4CO+)/(C6H5CO+)] values are well-correlated with the sigmap+ substituent constants. In the fragmentation of protonated acetophenones, deacetylation proceeds to give an intermediate proton-bound dimeric complex of ketene and benzene. The distribution of the product ions was found to depend on the proton affinities of ketene and substituted benzenes, and the kinetic method was applied in identifying the reaction intermediate. Protonated dibenzyl ether loses formaldehyde upon dealkylation, via an ion-neutral complex of the benzyloxymethyl cation and neutral benzene. These gas-phase retro-Friedel-Crafts reactions occurred as a result of the attack of the proton at the carbon atom to which the carbonyl or the methylene group is attached on the aromatic ring, which is described as the dissociative protonation site.     

O- versus F-protonation in (CF3CF2)2O and CF3OCF(CF3)2: a preliminary theoretical study

The relative modifications induced in the structure of perfluorodiethyl ether (CF₃CF₂)₂O and perfluoroisopropyl methyl ether CF₃OCF(CF₃)₂ by oxygen and fluorine protonation are studied at the RHF level with the 3–21G basis and correlated with their proton affinities and dissociation energies.     

Dissociative Benzyl Cation Transfer versus Proton Transfer: Loss of Benzene from Protonated N-Benzylaniline

In collisional activation of protonated N-benzylaniline, the benzene loss from the benzyl moiety is actually not the result of dissociative proton transfer (PT). In fact, benzyl cation transfer (BCT) from the nitrogen to the anilinic ring (ortho or para position) is the key step for benzene loss. Such dissociation occurs only after the benzyl group migrating from the site with the highest benzylation nucleophilicity (nitrogen) to a different one (aromatic ring carbon), which is described as dissociative benzyl cation transfer.     

Quantum Chemical Study of Hydroxyand Formyl-Substituted Benzenonium Ions

Substituted benzenonium ions (protonated benzene derivatives) model the intermediates in electrophilic aromatic substitution reactions. This paper presents a quantum chemical study at the MP2/6-31G* level of the various cations that could result from mono-protonation of phenol and benzaldehyde. Five isomeric ions were investigated in each case, the four benzenonium ions resulting from protonation at an ortho, meta, para, or ipso position, and the ion resulting from protonation at the oxygen. The results show the effects of the hydroxy and formyl substituents on the relative energies of the isomeric benzenonium ions. Wiberg bond orders and Reed–Weinhold (NPA or natural) atomic charges are also reported.     

Relationship between NMR shielding and heme binding strength for a series of 7-substituted quinolines

Chemical shielding tensors are calculated for the carbons in a series of 4-aminoquinolines with different substituents at the 7-position. The sigma(11) component is used as a measure of the relative pi-electron density at each carbon. By comparing the pi-electron density at each carbon with the log K of binding to heme (Kaschula et al. J. Med. Chem. 2002, 45, 3531), the drug-heme association is found to increase with increasing pi-electron density at the carbons meta to the substituent and with decreasing pi-electron density at the carbons ortho and para to the substituent. The greatest change in pi-electron density is at the ortho carbons, and log K increases with a decrease in pi-electron density on the ring containing the substituent, which corresponds to an increase in the pi-dipole between the two rings. An examination of the solution structures of the pi-pi complexes formed by amodiaquine and quinine with heme (Leed et al. Biochemistry 2002, 41, 10245. de Dios et al. Inorg. Chem. 2004, 43, 8078) shows that the pi-dipoles in each drug and in the porphyrin ring of heme may be paired. The chloro-substituted compound has an association constant that is an order of magnitude higher than the other compounds in the series, but the pi-electron density at the ring containing the substituent is not correspondingly low. This lack of correlation indicates that the Cl-substituted compound may be binding to heme in a manner that differs from the other compounds in the series.     

Proton-abstraction mechanism in the palladium-catalyzed intramolecular arylation: substituent effects

The regioselectivity observed in the intramolecular palladium-catalyzed arylation of substituted bromobenzyldiarylmethanes as well as theoretical results demonstrate that the Pd-catalyzed arylation proceeds by a mechanism involving a proton abstraction by the carbonate, or a related basic ligand. The reaction is facilitated by electron-withdrawing substituents on the aromatic ring, which is inconsistent with an electrophilic aromatic-substitution mechanism. The more important directing effect is exerted by electron-withdrawing substituents ortho to the reacting site.     

The use of molecular electrostatic potentials in the study of the protonation of toluene

The protonation of toluene has been studied using electrostatic potential plots. A basic assumption is that at the start of the reaction the aromatic hydrogen atom moves out of the plane of the ring forming a tetrahedral carbon. When the charges on the ortho, meta or para centres are considered alone ortho attack is predicted, whereas consideration of the potential due to the sum of the nuclear and electronic charges permits the interpretation of the preferred para-protonation of toluene.     

HZSM-5催化甲苯和甲醇烷基化反应机理的密度泛函理论研究

对二甲苯(PX)是重要的有机化工原料,主要用于生产对苯二甲酸(PTA)和对苯二甲酸二甲酯(DMT), PTA和 DMT可经缩聚生产化纤、合成树脂和塑料等聚酯产品. PX主要通过甲苯歧化、二甲苯异构化或甲苯与 C9芳烃烷基转移等方式生产.由于三种二甲苯和乙苯的沸点接近,需要经过吸附分离或深冷分离才能得到高纯度的 PX,传统工艺物料循环量大,设备庞大,操作费用高.而通过甲苯和甲醇烷基化反应直接高选择性生成 PX,可大大降低成本,具有非常高的经济效益和研究价值.自1970年代以来,国内外众多科研院所对甲苯和甲醇烷基化催化剂进行了广泛研究,但催化剂选择性和稳定性仍需进一步提高.为了加深对甲苯和甲醇烷基化反应的认识,指导催化剂开发,有必要对甲苯和甲醇烷基化生成二甲苯的反应机理进行深入研究.当前甲苯和甲醇烷基化机理研究主要存在以下问题：(1)计算得到的能量多为电子能,而非自由能;(2)所采用的模型多为团簇模型,使用 ONIOM方法,对长程作用力描述不充分;(3)认为甲苯只有一种吸附状态;(4)没有考虑偕烷基化反应.本文采用周期性模型,通过密度泛函理论研究了 HZSM-5分子筛上甲苯和甲醇烷基化反应机理,通过计算熵得到了反应自由能,并考虑了偕烷基化反应.由于甲基的存在,在甲苯的吸附态中,甲基会伸向孔道的不同方向,因此我们认为甲苯有多种吸附态,而不同的吸附态会生成不同的二甲苯.结果表明,甲苯可以在对位、间位、邻位和偕位上通过协同机理或分步机理发生烷基化反应.在协同机理中,甲苯在对位、间位、邻位和偕位发生烷基化反应的自由能垒分别为167,138,139和183 kJ/mol.在分步机理中,甲醇脱水生成甲氧基的自由能垒为145 kJ/mol,是决速步骤;而甲苯和甲氧基对位、间位、邻位和偕位烷基化的自由能垒分别为127,105,106和114 kJ/mol.两种机理中 PX的生成能垒均比 MX和 OX高,与文献报道的结果不同.文献均认为, PX的生成能垒最低.一方面这可能是由于所采用模型的不同,本文采用周期性模型,能更充分考虑长程作用力的影响;另一方面可能是由于对甲苯吸附态的不同处理,我们认为甲苯有多种吸附态,不同的吸附态会生成不同的二甲苯,而文献均只考虑了一种甲苯吸附态.但是,在实验中, PX选择性最高.这可能是由于：(1) PX在 HZSM-5孔道的扩散速率比 MX和 OX高2–3个数量级;(2)甲苯和甲醇烷基化生成的 MX和OX迅速发生异构化反应生成 PX,异构化反应速率高于甲苯烷基化速率.两种机理中, C8H11+都是重要的中间物种,它可以反馈一个质子给分子筛骨架,生成二甲苯;也可以脱烷基生成甲烷和乙烯等气相产物.研究发现,甲烷的生成是由于 C8H11+物种中的一个 H质子从苯环上的碳原子转移到甲基上的碳原子造成的,计算得到的对位、间位和邻位 C8H11+生成甲烷的能垒分别为136,132和134 kJ/mol.由于十元环孔道的限制, HZSM-5孔道中很难通过甲苯歧化反应生成苯;偕烷基化生成的碳正离子有可能脱烷基生成乙烯和乙烷等产物,进而生成苯.碳正离子脱烷基反应生成了大量气相产物,造成反应液收降低.碳正离子脱烷基反应与甲醇制烯烃过程的烃池机理相一致,因此甲苯和甲醇烷基化反应也遵循烃池机理.     

Protonation of thymine,cytosine, adenine,and guanine DNA nucleic acid bases: Theoretical investigation into the framework of density functional theory

Gradient-corrected density functional computations with triple-zeta-type basis sets were performed to determine the preferred protonation site and the absolute gas-phase proton affinities of the most stable tautomer of the DNA bases thymine (T), cytosine (C), adenine (A), and guanine (G). Charge distribution, bond orders, and molecular electrostatic potentials were considered to rationalize the obtained results. The vibrational frequencies and the contribution of the zero-point energies were also computed. Significant geometrical changes in bond lengths and angles near the protonation sites were found. At 298 K, proton affinities values of 208.8 (T), 229.1 (C), 225.8 (A), and 230.3 (G) kcal/mol were obtained in agreement with experimental results. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 989–1000, 1998     

Thermodynamics of the ionization of four difluorobenzoic and pentafluorobenzoic acids in water

Precision conductance measurements as a function of concentration and temperature between 0 and 100°C have been made for 2,3-, 2,5-, 3,4-, and 3,5-difluorobenzoic acids and pentafluorobenzoic acid in water. Standard state changes in enthalpy, entropy, and heat capacity as a function of temperature are reported for the ionization of these acids. Comparisons are made with other fluorobenzoic acids that have been reported earlier and with the corresponding methylbenzoic acids. The differences between the ionization of a fluorobenzoic acid and its counterpart methylbenzoic acid is almost entirely a difference in the entropies of ionization with only a small difference in the enthalpies of ionization. Each fluorine substituted in the meta or para position increases the entropy of ionization while substitution in the ortho position decreases the entropy. This is in contrast to the effect of methyl substitution where substitution in any position decreases the entropy of ionization. Walden products for the various anions follow the pattern found for the methylbenzoate anions with a sharp increase from 0 to about 30°C and with ortho substituted anions less mobile than those without ortho substitutents.     

偶氮染料在酸性介质中的电还原性质

研究了4个偶氮染料在酸性介质中的电还原性质。偶氮基在酸性介质中的还原均为不可逆四电子一步全还原。邻、对位上有吸电子基(如—CO_2Bu-n)的偶氮基较间位有吸电子基时更易被还原。分子中同时含有偶氮基和硝基时,偶氮基先被还原。     

The loss of carbon dioxide from activated perbenzoate anions in the gas phase: unimolecular rearrangement via epoxidation of the benzene ring

The unimolecular reactivities of a range of perbenzoate anions (X-C6H5CO3-), including the perbenzoate anion itself (X = H), nitroperbenzoates (X = para-, meta-, ortho-NO2), and methoxyperbenzoates (X = para-, meta-OCH3) were investigated in the gas phase by electrospray ionization tandem mass spectrometry. The collision-induced dissociation mass spectra of these compounds reveal product ions consistent with a major loss of carbon dioxide requiring unimolecular rearrangement of the perbenzoate anion prior to fragmentation. Isotopic labeling of the perbenzoate anion supports rearrangement via an initial nucleophilic aromatic substitution at the ortho carbon of the benzene ring, while data from substituted perbenzoates indicate that nucleophilic attack at the ipso carbon can be induced in the presence of electron-withdrawing moieties at the ortho and para positions. Electronic structure calculations carried out at the B3LYP/6-311++G(d,p) level of theory reveal two competing reaction pathways for decarboxylation of perbenzoate anions via initial nucleophilic substitution at the ortho and ipso positions, respectively. Somewhat surprisingly, however, the computational data indicate that the reaction proceeds in both instances via epoxidation of the benzene ring with decarboxylation resulting--at least initially--in the formation of oxepin or benzene oxide anions rather than the energetically favored phenoxide anion. As such, this novel rearrangement of perbenzoate anions provides an intriguing new pathway for epoxidation of the usually inert benzene ring.     

Physicochemical and structural properties of bacteriostatic sulfonamides: Theoretical study

A theoretical study at the Hartree–Fock and density functional theory levels is performed on sulfonamide‐type bacteriostatic compounds with the aim to provide an insight into their structure–activity relationship. The basicity of the p‐amino group is analyzed by means of the proton affinities and the protonation energies, showing that molecules presenting bacteriostatic activity are less basic, i.e., they are characterized by larger protonation energies and smaller proton affinities. The acidity of the amide group is analyzed through the deprotonation energy. The results reveal that the more acidic molecules present a larger bacteriostatic activity. This result is also confirmed from a study of bond orders. A bond order analysis of the amide group suggests that the electron attracting group in these molecules is responsible for the increase in acidity. The charge of the SO₂ group is also shown to be affected by the presence of the electron attracting group and consequently related to the acidity of the molecules. A geometric analysis shows that structures in which the amino group is more coplanar with respect to the benzenic ring possess larger bacteriostatic activity. A conformational analysis of these molecules illustrates that active molecules have relatively larger torsion energy barriers. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 94: 165–172, 2003