Gas‐phase fragmentations of N‐methylimidazolidin‐4‐one organocatalysts

N‐methylimidazolidin‐4‐one organocatalysts were studied in the gas phase. Protonated and sodium‐cationized (sodiated) molecules are conveniently accessible by electrospray mass spectrometry. Protonation enables three different closed‐shell paths of ring cleavage leading to iminium ions. The fragmentation pattern is largely unaffected by exocyclic substituents and thus is valuable to characterize the substance type as N‐methylimidazolidin‐4‐ones. Sodiated species show a distinctly different fragmentation that is less useful for characterization purposes: apart from signal loss due to dissociation of Na⁺, the observation of benzyl radical loss is by far predominant. Only in absence of a benzyl substituent, an analogue of the third ring cleavage (loss of [C₂H₅NO]) is observed. Copyright © 2017 John Wiley & Sons, Ltd.     

Charge transfer dissociation of phosphocholines: gas‐phase ion/ion reactions between helium cations and phospholipid cations

Phospholipid cations formed by electrospray ionization were subjected to excitation and fragmentation by a beam of 6 keV helium cations in a process termed charge transfer dissociation (CTD). The resulting fragmentation pattern in CTD is different from that of conventional collision‐induced dissociation, but analogous to that of metastable atom‐activated dissociation and electron‐induced dissociation. Like collision‐induced dissociation, CTD yields product ions indicative of acyl chain lengths and degrees of unsaturation in the fatty acyl moieties but also provides additional structural diagnostic information, such as double bond position. Although CTD has not been tested on a larger lipid sample pool, the extent of structural information obtained demonstrates that CTD is a useful tool for lipid structure characterization, and a potentially useful tool in future lipidomics workflows. CTD is relatively unique in that it can produce a relatively strong series of 2+ product ions with enhanced abundance at the double bond position. The generally low signal‐to‐noise ratios and spectral complexity of CTD make it less appealing than OzID or other radical‐induced methods for the lipids studies here, but improvements in CTD efficiency could make CTD more appealing in the future. Copyright © 2017 John Wiley & Sons, Ltd.     

Gas phase behavior of radical cations of perfluoroalkyl‐1,2,4‐triazines: an experimental and theoretical study

Electron ionization mass spectrometry and low‐energy collision‐induced decomposition reactions occurring in a tridimensional ion trap, together with density functional theory (DFT) calculations on neutrals, even‐ and odd‐electron cations, have been used to study the gas‐phase ion chemistry of a series of perfluoroalkyl‐1,2,4‐triazines. Loss of oxygen, due to thermal degradation occurring before ionization, likely involving the hydroxylamino group, has been observed. Compounds having a carbonyl group at position 6 of the triazine ring fragment in the source by elimination of NO followed by HF or CO. The decomposition pathways occurring due to CID experiments have shown interesting features depending on the nature and structure of precursor ions. Most of them involve elimination of endocyclic atoms, thereby producing contraction of the original six‐membered ring or formation of acyclic structures. DFT (B3LYP/6‐31G(d,p)) calculations have been used for evaluating structure, stability and properties of neutral and ionic species involved in gas‐phase processes. In particular, it has been calculated that in the molecular ion the unpaired electron is mainly located on the exocyclic nitrogen, while the positive charge is on the C(6) carbon atom. Copyright © 2009 John Wiley & Sons, Ltd.     

New polyelectrolytes based on 4‐vinyl‐1,2,3‐triazole and 1‐vinylimidazole

Copolymers of 4‐vinyl‐1,2,3‐triazole and 1‐vinylimidazole (VI) were obtained by radical copolymerization of (4‐vinyl‐1H‐1,2,3‐triazol‐1‐yl)methyl pivalate with VI followed by alkali hydrolysis. Reactivity ratios of the triazole and imidazole monomers are 0.51 and 0.30, respectively. Theoretical quantum‐chemical calculations by the PM3 semiempirical method give close values, which show that the obtained reactivity ratios reflect the activity of the vinyl groups. Polyelectrolyte properties of the copolymers were studied by potentiometric titration. Hydrogen bonds between the protonated triazole cycle and the triazole or imidazole units were found to considerably influence the solubility and solution properties of the copolymers. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Solvent‐Free One‐Step Photochemical Hydroxylation of Benzene Derivatives by the Singlet Excited State of 2,3‐Dichloro‐5,6‐dicyano‐p‐benzoquinone Acting as a Super Oxidant

Photoinduced hydroxylation of neat deaerated benzene to phenol occurred under visible‐light irradiation of 2,3‐dichloro‐5,6‐dicyano‐p‐benzoquinone (DDQ), which acts as a super photooxidant in the presence of water. Photocatalytic solvent‐free hydroxylation of benzene derivatives with electron‐withdrawing substituents such as benzonitrile, nitrobenzene, and trifluoromethylbenzene used as neat solvents has been achieved for the first time by using DDQ as a super photooxidant to yield the corresponding phenol derivatives and 2,3‐dichloro‐5,6‐dicyanohydroquinone (DDQH₂) in the presence of water under deaerated conditions. In the presence of dioxygen and tert‐butyl nitrite, the photocatalytic hydroxylation of neat benzene occurred with DDQ as a photocatalyst to produce phenol. The photocatalytic reactions are initiated by oxidation of benzene derivatives with the singlet and triplet excited states of DDQ to form the corresponding radical cations, which associate with benzene derivatives to produce the dimer radical cations, which were detected by the femto‐ and nanosecond laser flash photolysis measurements to clarify the photocatalytic reaction mechanisms. Radical cations of benzene derivatives react with water to yield the OH‐adduct radicals. On the other hand, DDQ ^{. ?} produced by the photoinduced electron transfer from benzene derivatives reacts with the OH‐adduct radicals to yield the corresponding phenol derivatives and DDQH₂. DDQ is recovered by the reaction of DDQH₂ with tert‐butyl nitrite when DDQ acts as a photocatalyst for the hydroxylation of benzene derivatives by dioxygen.     

Deactivation reactions in the modeled 2,2,6,6‐tetramethyl‐1‐piperidinyloxy‐mediated free‐radical polymerization of styrene: A comparative study with the 2,2,6,6‐tetramethyl‐1‐piperidinyloxy/acrylonitrile system

The competitiveness of the combination and disproportionation reactions between a 1‐phenylpropyl radical, standing for a growing polystyryl macroradical, and a 2,2,6,6‐tetramethyl‐1‐piperidinyloxy (TEMPO) radical in the nitroxide‐mediated free‐radical polymerization of styrene was quantitatively evaluated by the study of the transition geometry and the potential energy profiles for the competing reactions with the use of quantum‐mechanical calculations at the density functional theory (DFT) UB3‐LYP/6‐311+G(3df, 2p)//(unrestricted) Austin Model 1 level of theory. The search for transition geometries resulted in six and two transition structures for the radical combination and disproportionation reactions, respectively. The former transition structures, mainly differing in the out‐of‐plane angle of the N? O bond in the transition structure TEMPO molecule, were correlated with the activation energy, which was determined to be in the range of 8.4–19.4 kcal mol^?1 from a single‐point calculation at the DFT UB3‐LYP/6‐311+G(3df, 2p)//unrestricted Austin Model 1 level. The calculated activation energy for the disproportionation reaction was less favorable by a value of more than 30 kcal mol^?1 in comparison with that for the combination reaction. The approximate barrier difference for the TEMPO addition and disproportionation reaction was slightly smaller for the styrene polymerization system than for the acrylonitrile polymerization system, thus indicating that a β‐proton abstraction through a TEMPO radical from the polymer backbone could diminish control over the radical polymerization of styrene with the nitroxide even more than in the latter system. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 232–241, 2007     

Cooperative Activation with Chiral Nucleophilic Catalysts and N‐Haloimides: Enantioselective Iodolactonization of 4‐Arylmethyl‐4‐pentenoic Acids

Chiral triaryl phosphates promote the enantioselective iodolactonization of 4‐substituted 4‐pentenoic acids to give the corresponding iodolactones in high yields with high enantioselectivity. N‐Chlorophthalimide (NCP) is employed as a Lewis acidic activator and oxidant of I₂ for the present iodolactonization. In combination with 1.5 equivalents of NCP, only 0.5 equivalents of I₂ are sufficient to generate the iodinating reagent.     

Gas‐phase reactivity of 2‐hydroxy‐1,4‐naphthoquinones: a computational and mass spectrometry study of lapachol congeners

In order to understand the influence of alkyl side chains on the gas‐phase reactivity of 1,4‐naphthoquinone derivatives, some 2‐hydroxy‐1,4‐naphthoquinone derivatives have been prepared and studied by electrospray ionization tandem mass spectrometry in combination with computational quantum chemistry calculations. Protonation and deprotonation sites were suggested on the basis of gas‐phase basicity, proton affinity, gas‐phase acidity (ΔG_acid), atomic charges and frontier orbital analyses. The nature of the intramolecular interaction as well as of the hydrogen bond in the systems was investigated by the atoms‐in‐molecules theory and the natural bond orbital analysis. The results were compared with data published for lapachol (2‐hydroxy‐3‐(3‐methyl‐2‐butenyl)‐1,4‐naphthoquinone). For the protonated molecules, water elimination was verified to occur at lower proportion when compared with side chain elimination, as evidenced in earlier studies on lapachol. The side chain at position C(3) was found to play important roles in the fragmentation mechanisms of these compounds. Copyright © 2012 John Wiley & Sons, Ltd.     

Non-zwitterionic structures of aliphatic-only peptides mediated the formation and dissociation of gas phase radical cations

We have investigated how the non-zwitterionic and zwitterionic structures of aliphatic-only tripeptides affect the formation and dissociation of peptide radical cations in the gas phase. The non-zwitterionic forms of the aliphatic-only peptides in their metal complexes play an important role in determining whether the electron transfer pathway predominates. We extended this study by synthesizing permanent non-zwitterionic and zwitterionic forms of aliphatic-only peptide radical cations and exploring their reactivities in the gas phase. Collision-induced dissociation spectra demonstrated the feasibility of generating both non-zwitterionic and zwitterionic forms. Radical cations in zwitterionic forms may indeed mediate the beta and gamma carbon-carbon bond cleavages of leucine and isoleucine side chains from the GlyGlyXle radical peptides; this feature allows leucine and isoleucine residues to be distinguished unambiguously.     

Ambident PCN Heterocycles: N‐ and P‐Phosphanylation of Lithium 1,3‐Benzazaphospholides

Synthetic and structural aspects of the phosphanylation of 1,3‐benzazaphospholides 1_Li , ambident benzofused azaphosphacyclopentadienides, are presented. The unusual properties of phospholyl‐1,3,2‐diazaphospholes inspired us to study the coupling of 1_Li with chlorodiazaphospholene 2 , which led to the N‐substituted product 3 . Reaction of 1_Li with chlorodiphenyl‐ and chlorodicyclohexylphosphane likewise gave N‐phosphanylbenzazaphospholes 4 and 5 , whereas with the more bulky di‐tert‐butyl‐ and di‐1‐adamantylchlorophosphanes, the diphosphanes 6 and 7 are obtained; in the case of 7 they are isolated as a dimeric LiCl(THF) adduct. Structural information was provided by single‐crystal X‐ray diffraction and solution NMR spectroscopy experiments. 2D exchange spectroscopy confirmed the existence of two rotamers of the aminophosphane 5 at room temperature; variable‐temperature NMR spectroscopy studies of 6 revealed two dynamic processes, low‐temperature inversion at ring phosphorus (ΔH^≠=22 kJ mol^?1, ΔS^≠=2 J K^?1 mol^?1) and very low‐temperature rotation of the tBu₂P group. Quantum chemical studies give evidence that 2‐unsubstituted benzazaphospholides prefer N‐phosphanylation, even with bulky chlorophosphanes, and that substituents at the 2‐position of the heterocycle are crucial for the occurrence of P–N rotamers and for switching to alternative P‐substitution, beyond a threshold steric bulk, by both P‐ and 2‐position substituents.     

Photoinduced Radical Borylation of Alkyl Bromides Catalyzed by 4‐Phenylpyridine

Utilizing pyridine catalysis, we developed a visible‐light‐induced transition‐metal‐free radical borylation reaction of unactivated alkyl bromides that features a broad substrate scope and mild reaction conditions. Mechanistic studies revealed a novel nucleophilic substitution/photoinduced radical formation pathway, which could be utilized to trigger a variety of radical processes.     

Z and E rotamers of N‐formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one and their interconversion as studied by 1H/13C NMR spectroscopy and quantum chemical calculations

N‐Formyl‐1‐bromo‐4‐hydroxy‐3‐methoxymorphinan‐6‐one (compound 2 ), an important intermediate in the NIH Opiate Total Synthesis, presumably exists as a mixture of two rotamers (Z and E) in both CHCl₃ and DMSO at room temperature due to the hindered rotation of its N‐C18 bond in the amide moiety. By comparing the experimental ¹H and ¹³C chemical shifts of a single rotamer and the mixture of compound 2 in CDCl₃ with the calculated chemical shifts of the geometry optimized Z and E rotamers utilizing density functional theory, the crystalline rotamer of compound 2 was characterized as having the E configuration. The energy barrier between the two rotamers was also determined with the temperature dependence of ¹H and ¹³C NMR coalescence experiments, and then compared with that from the reaction path for the interconversion of the two rotamers calculated at the level of B3LYP/6‐31G*. Detailed geometry of the ground state and the transition states of both rotamers are given and discussed. Copyright © 2012 This article is a US Government work and is in the public domain in the USA.     

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.     

Influence of ionization on the conformational preferences of peptide models. Ramachandran surfaces of N‐formyl‐glycine amide and N‐formyl‐alanine amide radical cations

Ramachandran maps of neutral and ionized HCO–Gly–NH₂ and HCO–Ala–NH₂ peptide models have been built at the B3LYP/6‐31++G(d,p) level of calculation. Direct optimizations using B3LYP and the recently developed MPWB1K functional have also been carried out, as well as single‐point calculations at the CCSD(T) level of theory with the 6‐311++G(2df,2p) basis set. Results indicate that for both peptide models ionization can cause drastic changes in the shape of the PES in such a way that highly disallowed regions in neutral PES become low‐energy regions in the radical cation surface. The structures localized in such regions, and are highly stabilized due to the formation of 2‐centre‐3‐electron interactions between the two carbonyl oxygens. Inclusion of solvent effects by the conductor‐like polarizable continuum model (CPCM) shows that the solute‐solvent interaction energy plays an important role in determining the stability order. © 2008 Wiley Periodicals, Inc. J Comput Chem 2009     

Hypervalent radical formation probed by electron transfer dissociation of zwitterionic tryptophan and tryptophan‐containing dipeptides complexed with Ca2+ and 18‐crown‐6 in the gas phase

The relationship between peptide structure and electron transfer dissociation (ETD) is important for structural analysis by mass spectrometry. In the present study, the formation, structure and reactivity of the reaction intermediate in the ETD process were examined using a quadrupole ion trap mass spectrometer equipped with an electrospray ionization source. ETD product ions of zwitterionic tryptophan (Trp) and Trp‐containing dipeptides (Trp‐Gly and Gly‐Trp) were detected without reionization using non‐covalent analyte complexes with Ca²⁺ and 18‐crown‐6 (18C6). In the collision‐induced dissociation, NH₃ loss was the main dissociation pathway, and loss related to the dissociation of the carboxyl group was not observed. This indicated that Trp and its dipeptides on Ca²⁺(18C6) adopted a zwitterionic structure with an NH₃⁺ group and bonded to Ca²⁺(18C6) through the COO^? group. Hydrogen atom loss observed in the ETD spectra indicated that intermolecular electron transfer from a molecular anion to the NH₃⁺ group formed a hypervalent ammonium radical, R‐NH₃, as a reaction intermediate, which was unstable and dissociated rapidly through N–H bond cleavage. In addition, N–C_α bond cleavage forming the z₁ ion was observed in the ETD spectra of Trp‐GlyCa²⁺(18C6) and Gly‐TrpCa²⁺(18C6). This dissociation was induced by transfer of a hydrogen atom in the cluster formed via an N–H bond cleavage of the hypervalent ammonium radical and was in competition with the hydrogen atom loss. The results showed that a hypervalent radical intermediate, forming a delocalized hydrogen atom, contributes to the backbone cleavages of peptides in ETD. Copyright © 2015 John Wiley & Sons, Ltd.     

2,2,2‐Trifluoroacetophenone as an Organocatalyst for the Oxidation of Tertiary Amines and Azines to N‐Oxides

A cheap, mild and environmentally friendly oxidation of tertiary amines and azines to the corresponding N‐oxides is reported by using polyfluoroalkyl ketones as efficient organocatalysts. 2,2,2‐Trifluoroacetophenone was identified as the optimum catalyst for the oxidation of aliphatic tertiary amines and azines. This oxidation is chemoselective and proceeds in high‐to‐quantitative yields utilizing 10 mol % of the catalyst and H₂O₂ as the oxidant.