Similarities and differences in the electron ionization-induced fragmentation of structurally related N-alkoxymethyl lactams and sultams

Unimolecular fragmentation patterns of the molecular ions of selected lactams and sultams bearing alkoxymethyl group at the nitrogen atom were studied. The main common fragmentation reaction observed for all compounds studied in this work is the elimination of an aldehyde molecule. This reaction is considered to proceed via two different mechanisms. For lactams, hydrogen rearrangement within an alkoxymethyl group is observed, which leads to the appropriate N-methyl derivatives. For sultams, transfer of the methyl group to the nitrogen and oxygen atoms, proceeding through an ion-neutral complex, dominates. Another important fragmentation channel characteristic exclusively for lactams is the loss of an alkyl radical. This process takes place within the N-alkoxymethyl moiety, yielding the appropriate protonated ion of N-formyllactams. This process is accompanied by relatively high kinetic energy release.     

Substituent effect on the reaction mechanism of proton transfer in formamide

MP2 and B3LYP methods at 6‐311++G** basis set have been used to explore proton transfer in keto‐enol forms of formamide and to investigate the effect of substituent, i.e., H, F, Cl, OH, SH, and NH₂ on their transition states. Additionally, the vibrational frequencies of aforementioned compounds are calculated at the same levels of theory. It is proposed that the barrier heights values in kJ/mol for F, Cl, OH, and SH substituents are significantly greater than that of the bare tautomerization reaction, implying the importance of the substituents effect on the intramolecular proton transfer. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2012     

Ionization and protonation of MgC3: A theoretical study

A theoretical study of the MgC₃⁺ and MgC₃H⁺ species has been carried out. Predictions for their geometries and vibrational frequencies have been made at both second‐order Møller–Plesset (MP2) and B3LYP levels, whereas electronic energies have been computed at G2 and coupled cluster single and double excitation model augmented with a noniterative triple excitation conection (CCSD(T)) levels. The predicted global minimum for MgC₃⁺ is a rhombic structure (²A₁ electronic state), whereas a T‐shaped structure and an open‐chain isomer lie about 10 and 12 kcal/mol, respectively, higher in energy. In the case of MgC₃H⁺ the predicted global minimum is also a four‐membered ring obtained upon protonation of the most stable neutral isomer. Low ionization potentials and high proton affinities are generally obtained, especially for the most stable MgC₃⁺ isomer. The estimated values at the CCSD(T) level for the predicted global minimum are 7.20 eV [ionization potential (IP)] and 256.5 kcal/mol [proton affinities (PA)]. Therefore, if present in the interstellar medium, MgC₃ should be easily ionized and would react quite easily to give the protonated species. © 2002 John Wiley & Sons, Inc. Int J Quantum Chem, 2001     

Gas phase retro‐Michael reaction resulting from dissociative protonation: fragmentation of protonated warfarin in mass spectrometry

A mass spectrometric study of protonated warfarin and its derivatives (compounds 1 to 5) has been performed. Losses of a substituted benzylideneacetone and a 4‐hydroxycoumarin have been observed as a result of retro‐Michael reaction. The added proton is initially localized between the two carbonyl oxygens through hydrogen bonding in the most thermodynamically favorable tautomer. Upon collisional activation, the added proton migrates to the C‐3 of 4‐hydroxycoumarin, which is called the dissociative protonation site, leading to the formation of the intermediate ion‐neutral complex (INC). Within the INC, further proton transfer gives rise to a proton‐bound complex. The cleavage of one hydrogen bond of the proton‐bound complex produces the protonated 4‐hydroxycoumarin, while the separation of the other hydrogen bond gives rise to the protonated benzylideneacetone. Theoretical calculations indicate that the 1, 5‐proton transfer pathway is most thermodynamically favorable and support the existence of the INC. Both substituent effect and the kinetic method were utilized for explaining the relative abundances of protonated 4‐hydroxycoumarin and protonated benzylideneacetone derivative. For monosubstituted warfarins, the electron‐donating substituents favor the generation of protonated substituted benzylideneacetone, whereas the electron‐withdrawing groups favor the formation of protonated 4‐hydroxycoumarin. Copyright © 2012 John Wiley & Sons, Ltd.     

Theoretical studies on the structure and protonation of Cu(II) complexes of a series of tripodal aliphatic tetraamines: Good correlations with the experimental data

DFT(B3LYP) studies on first protonation step of a series of Cu(II) complexes of some tripodal tetraamines with general formula N[(CH₂)_nNH₂][(CH₂)_mNH₂][(CH₂)_pNH₂] (n = m = p = 2, tren; n = 3, m = p = 2, pee; n = m = 3, p = 2, ppe; n = m = 3, tpt; n = 2, m = 3, p = 4, epb; and n = m = 3, p = 4; ppb) are reported. First, the gas‐phase proton macroaffinity of all latter complexes was calculated with considering following simple reaction: [Cu(L)]²⁺(g) + H⁺(g) → [Cu(HL)]³⁺(g). The results showed that there is a good correlation between the calculated proton macroaffinities of all complexes with their stability constants in solution. Then, we tried to determine the possible reliable structures for microspecies involved in protonation process of above complexes. The results showed that, similar to the solid state, the [Cu(L)(H₂O)]²⁺ and [Cu(HL)(H₂O)₂]³⁺ are most stable species for latter complexes and their protonated form, respectively, at gas phase. We found that there are acceptable correlations between the formation constants of above complexes with both the ? and ? of following reaction: [Cu(L)(H₂O)]²⁺(g) + H⁺(g) + H₂O(g) → [Cu(HL)(H₂O)₂]³⁺(g). The ? of the latter reaction can be defined as a theoretically solvent–proton macroaffinity of reactant complexes because they have gained one proton and one molecule of the solvent. The unknown formation constant of [Cu(epb)]²⁺ complex was also predicted from the observed correlations. In addition, the first proton affinity of all complexes was studied in solution using DPCM and CPCM methods. It was shown that there is an acceptable correlation between the solvent–proton affinities of [Cu(L)(H₂O)]²⁺ complexes with formation constants of [Cu(HL)(H₂O)₂]³⁺ complexes in solution. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010     

Ortho‐hydroxyl effect and proton transfer via ion–neutral complex: the fragmentation study of protonated imine resveratrol analogues in mass spectrometry

The fragmentation pathways of protonated imine resveratrol analogues in the gas‐phase were investigated by electrospray ionization–tandem mass spectrometry. Benzyl cations were formed in the imine resveratrol analogues that had an ortho‐hydroxyl group on the benzene ring A. The specific elimination of the quinomethane neutral, CH₂ = C₆H₄ = O, from the two isomeric ions [M1 + H]⁺ and [M3 + H]⁺ via the corresponding ion–neutral complexes was observed. The fragmentation pathway for the related meta‐isomer, ion [M2 + H]⁺ and the other congeners was not observed. Accurate mass measurements and additional experiments carried out with a chlorinated analogue and the trideuterated isotopolog of M1 supported the overall interpretation of the fragmentation phenomena observed. It is very helpful for understanding the intriguing roles of ortho‐hydroxyl effect and ion–neutral complexes in fragmentation reactions and enriching the knowledge of the gas‐phase chemistry of the benzyl cation. Copyright © 2016 John Wiley & Sons, Ltd.     

Polar substituent effect of the ester group on conformational equilibria of O-mono-substituted cyclohexanes—the para-substituent effect in cyclohexyl benzoates

Together with the nonsubstituted reference compound, para-methoxy- and para-nitro cyclohexyl benzoates have been synthesized and their conformational equilibria studied by low temperature NMR spectroscopy and theoretical DFT calculations. The free energy differences ΔG° between axial and equatorial conformers were examined with respect to polar substituent influences on the conformational equilibrium of O-mono-substituted cyclohexane.     

Structure, reactivity and thermochemical properties of protonated lactic acid

The protonation energetics of lactic acid (LA) were experimentally determined by the kinetic method including the entropy effect. The values (proton affinity, PA(LA) = 817.4 +/- 4.3 kJ mol(-1); protonation entropy, DeltaS degrees (p)(LA) = -2 +/- 5 J K(-1) mol(-1); gas-phase basicity, GB(LA) = 784.5 +/- 4.5 kJ mol(-1)) agree satisfactorily with computed G2(MP2) expectations (PA(LA) = 811.8 kJ mol(-1); DeltaS degrees (p)(LA) = -7.1 J K(-1) mol(-1); GB(LA) = 777.4 kJ mol(-1)). The fragmentation behaviour of protonated lactic acid (LAH(+)) is dominated by carbon monoxide loss followed by elimination of a water molecule. Direct dehydration of LAH(+) is only a high-energy process hardly competitive with the CO loss. A complete mechanistic scheme, based on MP2/6-31G* calculations, is proposed; it involves isomerization of the various protonated forms of LA and the passage through the ion-neutral complex between the 2-hydroxypropyl acylium cation and a water molecule.     

A counterintuitive structural effect of metal-metal bond protonation and its electronic underpinnings

Protonation across the metal-metal bond in the complexes [(CO)(2)M(mu-dppm)(mu-PtBu(2))(mu-H)M(CO)(2)] (M=Fe or Ru, dppm=Ph(2)PCH(2)PPh(2)) induces M-M bond shortening of up to about 0.05 A. DFT calculations on simplified iron models reproduce this trend well. Conversely, the computations show that the M-M distance in the dimer [{Cp*Ir(CO)}(2)] lengthens with two consecutive protonations, but there are no crystal structure determinations to highlight the effects on the Ir-Ir bond. DFT calculations and the analogous cobalt system confirm that the transformation of a two-electron, two-center (2e-2c) bond into a 2e-3c bond is accompanied by the predicted elongation. An MO analysis indicated similar nature and evolution of the M-M bonding these cases. In particular, the HOMOs of the mono-hydrido cations [Cp(CO)M(mu-H)M(CO)Cp](+) (M=Ir, Co) have evident M-M bent-bond character, and hence subsequent protonation invariably causes a decrease in the bond index. The Fe(2) and Co(2) systems have also been analyzed with the quantum theory of atoms in molecules (QTAIM) method, but in no case was an M-M bond critical point located unless an artificially shorter M-M distance was imposed. However, the trends for the atoms-in-molecules (AIM) bond delocalization indexes delta(M-M) confirm the overall M-M bond weakening on protonation. In conclusion, all the computational results for the iron system indicate that the paradigm of a direct correlation between bond strength and distance is not always applicable. This is attributable to a very flat potential energy surface and various competing effects imposed by the bridging ligands.     

Ab initio and experimental thermodynamic and kinetic study of proton-assisted bond activation in gaseous hydrocarbons: deconvolution of reaction efficiencies in the case of adamantane

1) Protonation at all possible sites of adamantane (C(10)H(16)) was studied at the MP2/6-311++G(3df,2p)//MP2/6-311++G(d,p) level. This provided values of the changes in the thermodynamic state functions for these processes. Whenever direct comparison was possible, the agreement with experimental data was very good. 2) By the same means, the reaction paths linking the various species obtained in these reactions were analyzed. 3) Fourier transform ion cyclotron resonance (FT-ICR) spectroscopy was used to determine the rate constants for proton transfer from 16 protonated reference bases to adamantane in the gas phase. Also, the rate constants for the formation of ionic products in these reactions were determined. 4) The experimental reaction rates were successfully predicted and refined on the basis of a simple mechanistic model based on the reaction profiles indicated above. 5) Our results hint at the potential usefulness of this approach for mechanistic studies.     

Theoretical Investigation of the Additivity of Structural Substituent Effects in Benzene Derivatives

The additivity of substituent effects in 1,3- and 1,4-disubstituted C₆H₄X₂, and 1,3,5-trisubstituted C₆H₃X₃ (X=F, Cl, CN, NO₂, CH₃, CF₃, NH₂, OH) benzene derivatives on the ring geometry has been investigated. The analysis is based on ab initio calculations at the MP2/6-31G** level of theory. The substituent impacts on the benzene ring are generally in good agreement with the results reported in earlier experimental and lower level theoretical studies. The impacts determined in the monosubstituted benzenes were used to estimate the ring distortions in the di- and trisubstituted derivatives. The estimated ring CC bond distances agree generally within 0.001 Å and the estimated CCC bond angles within 0.3 degree, with the optimized ones. The best agreement (deviations up to only 0.0003 Å and 0.03 deg.) between the estimated and optimized geometrical parameters was obtained for the CH₃ derivatives. Generally, the para-disubstituted derivatives showed the best compliance with additivity, somewhat poorer agreement characterized the meta derivatives while the trisubstituted derivatives showed angular distortions of up to about 0.4°.     

A ‘meta effect’ in the fragmentation reactions of ionised alkyl phenols and alkyl anisoles

The competition between benzylic cleavage (simple bond fission [SBF]) and retro‐ene rearrangement (RER) from ionised ortho, meta and para RC₆H₄OH and RC₆H₄OCH₃ (R = n‐C₃H₇, n‐C₄H₉, n‐C₅H₁₁, n‐C₇H₁₅, n‐C₉H₁₉, n‐C₁₅H₃₁) is examined. It is observed that the SBF/RER ratio is significantly influenced by the position of the substituent on the aromatic ring. As a rule, phenols and anisoles substituted by an alkyl group in meta position lead to more abundant methylene‐2,4‐cyclohexadiene cations (RER fragmentation) than their ortho and para homologues. This ‘meta effect’ is explained on the basis of energetic and kinetic of the two reaction channels. Quantum chemistry computations have been used to provide estimate of the thermochemistry associated with these two fragmentation routes. G3B3 calculation shows that a hydroxy or a methoxy group in the meta position destabilises the SBF and stabilises the RER product ions. Modelling of the SBF/RER intensities ratio has been performed assuming two single reaction rates for both fragmentation processes and computing them within the statistical RRKM formalism in the case of ortho, meta and para butyl phenols. It is clearly demonstrated that, combining thermochemistry and kinetics, the inequality (SBF/RER)_meta < (SBF/RER)_ortho < (SBF/RER)_para holds for the butyl phenols series. It is expected that the ‘meta effect’ described in this study enables unequivocal identification of meta isomers from ortho and para isomers not only of alkyl phenols and alkyl anisoles but also in other alkyl benzene series. Copyright © 2012 John Wiley & Sons, Ltd.     

Resonance Raman spectroscopy and DFT calculations of the protonation of 4-(2-pyridylazo)-N,N-dimethylaniline in solution and adsorbed on oxide surfaces

The protonation of 4-(2-pyridylazo)-N,N-dimethylaniline (PYAD) in aqueous solution and its adsorption on oxide surfaces has been studied by resonance Raman (RR) spectroscopy. The gas phase structures of neutral, protonated and diprotonated forms of PYAD were modelled by SCF-DFT calculations at the B3-LYP/DZ level, enabling determination of the simulated vibrational spectra of these species, together with vibrational assignments, and providing confirmation that protonation occurs initially at the pyridyl nitrogen atom. Electronic absorption spectra were interpreted using time-dependent DFT calculations. Adsorption of PYAD on SiO₂ or Al₂O₃ surfaces is mainly via the neutral species, hydrogen bonded to surface OH groups, although a small proportion of adsorbed molecules are protonated. By contrast, adsorption on SiO₂–Al₂O₃ results in complete protonation, indicating the presence of Brønsted acidic sites with pK_a values ? 4.5, whereas adsorption on H-mordenite results in diprotonation, indicating the presence of Brønsted acidic sites with pK_a values ? 2.     

Intramolecular electrophilic aromatic substitution in gas-phase-protonated difunctional compounds containing one or two arylmethyl groups

A variety of dibenzyl esters and ethers undergo a rearrangement process upon isobutane chemical ionization and collision-induced dissociation of their MH(+) ions, whereby a new bond is formed between the two benzyl groups, giving rise to abundant [C(14)H(13)](+) (m/z 181) ions. This rearrangement has been explained as an intramolecular electrophilic substitution in the gas phase occurring in an ion-neutral complex formed by the cleavage of one of the benzyl-oxygen bonds. A similar highly efficient intramolecular electrophilic substitution takes place in di-alpha- and beta-naphthylmethyl adipates affording m/z 281 [C(22)H(17)](+) ions, but not in the sterically hindered di-9-anthracylmethyl adipate. An analogous efficient rearrangement occurs in benzyl alpha- and beta-naphthylmethylcyclohexane-1,4-dicarboxylates and in benzyl alpha- and beta-phenylethylcyclohexane-1,4-dimethanol ethers. The analogous rearrangement is much less efficient in benzylallyl, benzylpropargyl and benzyl-9-anthracylmethyl derivatives, even less in benzylisopropyl and benzylacetyl analogs, and it is absent in benzyltetrahydropyranyl derivatives. The distinctive behavior of the protonated difunctional benzyl derivatives is interpreted in terms of the energy requirements of the O-R bond heterolysis of the protonated functionalities, the ability of the neutral R' groups (non-dissociated from the oxygen atom) to play the role of the nucleophile in the intramolecular electrophilic substitution processes and the electrophilicity of the R(+) ions.     

Coordination of triply charged lanthanum in the gas phase: theory and experiment

Ion-molecule reactions between complexes [La(CH3CN)n]3+ (n=6-9) or [La(NC(CH2)4CN)n]3+ (n=3-4) and water were studied at low collision energies in the second quadrupole of a tandem mass spectrometer. The products [La(CH3CN)p(H2O)8-p]3+ (p=6-8) and [La(NC(CH2)4CN)q(H2O)8-2q]3+ (q=3-4) had the highest relative abundances. This strongly suggests that the preferred coordination number of La3+ is eight. Similarly, the coordination number of Ca2+ was re-examined both experimentally and theoretically, and was found to be six, in good agreement with previous observations. Density functional calculations provide strong evidence that the primary solvation shell of [La(L)n]3+ consists of eight ligands; additional ligands reside in a second solvation shell and are hydrogen bonded to one or two water molecules in the first shell.     

A DFT study of proton transfers for the reaction of phenol and hydroxyl radical leading to dihydroxybenzene and H2O in the water cluster

Reactions of phenol and hydroxyl radical were studied under the aqueous environment to investigate the antioxidant characters of phenolic compounds. M06‐2X/6‐311 + G(d,p) calculations were carried out, where proton transfers via water molecules were examined carefully. Stepwise paths from phenol + OH^• + (H₂O)_n (n = 3, 7, and 12) to the phenoxyl radical (Ph O^•) via dihydroxycyclohexadienyl radicals (ipso, ortho, meta, and para OH‐adducts) were obtained. In those paths, the water dimer was computed to participate in the bond interchange along hydrogen bonds. The concerted path corresponding to the hydrogen atom transfer (HAT, apparently Ph OH + OH^• → Ph O^• + H₂O) was found. In the path, the hydroxyl radical located on the ipso carbon undergoes the charge transfer to prompt the proton (not hydrogen) transfer. While the present new mechanism is similar to the sequential proton loss electron transfer (SPLET) one, the former is of the concerted character. Tautomerization reactions of ortho or para (OH)C₆H₅=O + (H₂O)_n → C₆H₄(OH)₂(H₂O)_n were traced with n = 2, 3, 4, and 14. The n = 3 (and n = 14) model of ortho and para was calculated to be most likely by the strain‐less hydrogen‐bond circuit.     

The effect of fluorination: a crystallographic and computational study of mesogenic alkyl 4-[2-(perfluorooctyl)ethoxy]benzoates

The series of alkyl 4-[2-(perfluorooctyl)ethoxy]benzoates (F8-n) shows a systematic change of crystal structures depending on the length of the alkyl chain: separate packing of perfluorooctyl (Rf) and alkyl (Rh) chains from each other for shorter (n=2) and longer (n=11) members, alternate packing of Rf and Rh chains for middle (n=6,7) members, and an intermediate type of packing for n=4. Semiempirical MO calculations show slightly repulsive interactions between the Rf chains, and attractive ones between Rf and Rh chains and between Rh and the core of a molecular pair. It is concluded that fluorination determines the molecular shape of the crystal structures by making the chain rigid. It is confirmed that the interactions between Rf chains are small compared with those between other moieties and that they are forced to aggregate owing to the exclusion from other moieties. Thus, the effect is dependent on the geometries and intermolecular interactions of the other moieties.     

Theoretical study of one‐carbon unit transfer between methyl‐AICA and N1‐methyl‐N1‐acryloyl‐formamide

The mechanism of one‐carbon unit transfer between 1‐methyl‐5‐amino‐4‐carboxamide imidazole (M‐AICA) and N¹‐methyl‐N¹‐acryloyl‐formamide (the model molecule of 10‐f‐H4F) is investigated by the Hartree–Fock and DFT methods, respectively, at the 6‐31G* basis level. There are two different channels for the proton transfer, resulting in two reaction pathways with different properties. The results indicate that both channels can complete the reaction, but path a is slightly favored due to its lower active energy barrier. Furthermore, the influence of 4‐carboxamindde in M‐AICA is also discussed. This group can stabilize the reactant and intermediates, and reduce the active energy barrier through the intermolecular hydrogen bond. The intermolecular hydrogen bond results in an enlarged conjugation system and makes the transition states more stable. Our results are in agreement with experiments. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005     

Gas-phase reactivity of the O=P(OCH3)2 + phosphonium ion towards alpha,beta-unsaturated esters in a quadrupole ion trap

Ion-molecule reactions between the O=P(OCH3)2 + phosphonium ions and eight alpha,beta-unsaturated esters (methyl acrylate, ethyl acrylate, methyl crotonate, ethyl crotonate, methyl 3,3-dimethylacrylate, ethyl 3,3-dimethylacrylate, methyl methacrylate and ethyl methacrylate) were performed in a quadrupole ion trap mass spectrometer. The O=P(OCH3)2 + phosphonium ions, formed by electron ionization from neutral trimethyl phosphite, were found to react with alpha,beta-unsaturated esters to give an adduct [RR'C=CR'COOR', O=P(OCH3)2]+, which lose spontaneously a molecule of trimethyl phosphate (R'=CH3) or dimethyl ethyl phosphate (R'=C2H5). An ion corresponding to a protonated trialkyl phosphate is also observed when substituent R'=H. To confirm the experimental results, and to elucidate the mechanism for the formation of the ionic species, a theoretical study using the density functional theory (DFT) approach was carried out. The potential energy surface obtained from B3LYP/6-31G(d,p) calculations for the reaction between O=P(OCH3)2 + and methyl acrylate is described.