Unusual cross-ring S(N)2 reactions of M-H (-) ions of methoxyacetanilides

Deprotonated o, m-, and p-methoxyacetanilide show pronounced peaks in their collision-induced tandem mass spectra (MS/MS) produced by losses of the elements of C2H6. It is proposed that this reaction is a 'cross-ring' internal S(N)2 reaction involving an incipient methyl anion. For example, p-CH3O-C6H4-N--CO-CH3--> [(p.CH3O-C6H4-N=C=O)CH3-]--> O---C6H4-N=C=O+C2H6.

Association between neuropathic pain and A-Waves in Leprosy patients with type 1 and 2 reactions

Summary: Neuropathic pain (NP) is a well-recognized feature of leprosy neuropathy. However, the diagnosis of NP is difficult using only clinical criteria. In the study reported here, by means of conventional nerve conduction studies, the authors sought for an association between long-latency responses and NP complaints in leprosy patients with type 1 and 2 reactions. Of the 27 ulnar nerves of leprosy patients, 18 with type 1 reaction (T1R) and 9 with type 2 reaction (T2R) were followed-up for 6 months before and after steroid treatment. Clinical characteristics of pain complaints and clinical function were assessed, as well as the presence of F- and A-waves of the ulnar nerve using nerve conduction studies. The clinical and the neurophysiologic findings were compared to note positive concordances (presence of NP and A-waves together) and negative concordances (absence of NP and A-waves together) before and after treatment. Both reactions presented a high frequency of A-waves (61.1% in T1R and 66.7% in T2R, P < 0.05) and prolonged F-waves (69.4% in T1R and 65.8% in T2R, P = 0.4). No concordances were seen between pain complaints and F-waves. However, significant concordances between NP and A-waves were observed, although restricted to the T2R group ([chi]2 = 5.65, P = 0.04). After treatment, there was a significant reduction in pain complaints, as well as the presence of F- and A-waves in both groups (P < 0.05 for all comparisons). In conclusion, the presence of A-waves correlates well with pain complaints of neuropathic characteristics in leprosy patients, especially in those with type 2 reaction. Probably, such response shares similar mechanisms with the small-fiber dysfunction seen in these patients with NP, such as demyelination, intraneural edema, and axonal sprouting. Further studies using specific tools for small-fiber assessment are warranted to confirm our findings.

Reactions of methylvinyl and phenylvinyl ketones with a tricyclic ketone derived from 2-tetralone: characterization of crystalline products by X-ray diffraction

Base catalysed reaction of the tricyclic ketone (6 ⇌ 7) with methylvinyl ketone gave the tetracyclic ketols, 11, 13, 15, 16, and the pentacyclic ketols, 12, 17. With phenylvinyl ketone, the tetracyclic ketol (18) was formed. The stereostructures of the ketols were identified by X-Ray diffraction. The base-catalysed title reactions gave the cyclic ketols and derived compounds shown below whose structures were identified by X-ray diffraction.

Reactions of the hydroperoxide anion with dimethyl methylphosphonate in an ion trap mass spectrometer : evidence for a gas phase alpha-effect

The gas phase degradation reactions of the chemical warfare agent (CWA) simulant, dimethyl methylphosphonate (DMMP), with the hydroperoxide anion (HOO(-)) were investigated using a modified quadrupole ion trap mass spectrometer. The HOO(-) anion reacts readily with neutral DMMP forming two significant product ions at m/z 109 and m/z 123. The major reaction pathways correspond to (i) the nucleophilic substitution at carbon to form \[CH(3)P(O)(OCH(3))O](-) (m/z 109) in a highly exothermic process and (ii) exothermic proton transfer. The branching ratios of the two reaction pathways, 89% and 11% respectively, indicate that the former reaction is significantly faster than the latter. This is in contrast to the trend for the methoxide anion with DMMP, where proton transfer dominates. The difference in the observed reactivities of the HOO(-) and CH(3)O(-) anions can be considered as evidence for an a-effect in the gas phase and is supported by electronic structure calculations at the B3LYP/aug-cc-pVTZ//B3LYP/6-31+G(d) level of theory that indicate the S(N)2(carbon) process has an activation energy 7.8 kJ mol(-1) lower for HOO(-) as compared to CH(3)O(-). A similar alpha-effect was calculated for nucleophilic addition-elimination at phosphorus, but this process an important step in the perhydrolysis degradation of CWAs in solution - was not observed to occur with DMMP in the gas phase. A theoretical investigation revealed that all processes are energetically accessible with negative activation energies. However, comparison of the relative Arrhenius pre-exponential factors indicate that substitution at phosphorus is not kinetically competitive with respect to the S(N)2(carbon) and deprotonation processes.

Ion-molecule reactions of O,S-Dimethyl methylphosphonothioate : Evidence for intramolecular sulfur oxidation during VX perhydrolysis

The alkaline perhydrolysis of the nerve agent O-ethyl S-[2-(diisopropylamino)ethyl] methylphosphonothioate (VX) was investigated by studying the ion-molecule reactions of HOO(-) with O,S-dimethyl methylphosphonothioate in a modified linear ion-trap mass spectrometer. In addition to simple proton transfer, two other abundant product ions are observed at m/z 125 and 109 corresponding to the S-methyl methylphosphonothioate and methyl methylphosphonate anions, respectively. The structure of these product ions is demonstrated by a combination of collision-induced dissociation and isotope-labeling experiments that also provide evidence for their formation by nucleophilic reaction pathways, namely, (i) S(N)2 at carbon to yield the S-methyl methylphosphonothioate anion and (ii) nucleophilic addition at phosphorus affording a reactive pentavalent intermediate that readily undergoes internal sulfur oxidation and concomitant elimination of CH(3)SOH to yield the methyl methylphosphonate anion. Consistent with previous Solution phase observations of VX perhydrolysis, the toxic P-O cleavage product is not observed in this VX model system and theoretical calculations identify P-O cleavage to be energetically uncompetitive. Conversely, intramolecular sulfur oxidation is calculated to be extremely exothermic and kinetically accessible explaining its competitiveness with the facile gas phase proton transfer process. Elimination of a sulfur moiety deactivates the nerve agent VX and thus the intramolecular sulfur oxidation process reported here is also able to explain the selective perhydrolysis of the nerve agent to relatively nontoxic products.

Interaction of H-2 with transition metal homonuclear dimers Cu-2, Ag-2, Au-2 and heteronuclear dimers PdCu, PdAg and PdAu

The reaction mechanisms of the H-2 with the homonuclear dimers M-2 (Cu, Ag, Au) and the heteronuclear dimers PdM (M = Cu, Ag, Au) were studied by use of density functional theory. For the H-2 reactions with homonuclear dimers M-2 (Cu, Ag, Au), it was found that it is easier for Au-2 to dissociate the hydrogen molecule compared with Cu-2 and Ag-2. For H-2 reactions with the heteronuclear dimers PdM (M = Cu, Ag, An), the hydrogen molecule can be easily dissociated at Pd site, rather than at noble metal site.

Reactions of nitrogen nucleophiles with enantiopure cyclohexenyl electrophiles:a stereo- and regio- selective study

The reactions of enantiopure cyclohexene epoxides and trans-1,2-bromoacetates, derived from the corresponding substituted benzene cis-dihydrodiol metabolites, with nitrogen nucleophiles, were examined and possible mechanisms proposed. An initial objective was the synthesis of new 1,2-aminoalcohol enantiomers as potential chiral ligands and synthetic scaffolds for library generation. These apparently simple substitution reactions proved to be more complex than initially anticipated and were found to involve a combination of different reaction mechanisms. Allylic trans-1,2-azidohydrins were prepared by Lewis acid-catalysed ring-opening of cyclic vinyl epoxides with sodium azide via an S(N)2 mechanism. On heating, these trans-1,2-azidohydrins isomerized to the corresponding trans-1,4-azidohydrins via a suprafacial allyl azide [3,3]-sigmatropic rearrangement mechanism. Conversion of a 1,2-azidohydrin to a 1,2-azidoacetate moved the equilibrium position in favour of the 1,4-substitution product. Allylic trans-1,2-bromoacetates reacted with sodium azide at room temperature to give C-2 and C-4 substituted products. A clean inversion of configuration at C-2 was found, as expected, from a concerted S(N)2-pathway. However, substitution at C-4 was not stereoselective and resulted in mixtures of 1,4-cis and 1,4-trans products. This observation can be rationalized in terms of competitive S(N)2 and S(N)2 reactions allied to a [3,3]-sigmatropic rearrangement. cis-1,2-Azidohydrins and cis-1,2-azidoacetates were much more prone to rearrange than the corresponding trans-isomers. Reaction of the softer tosamide nucleophile with trans-1,2-bromoacetates resulted, predominantly, in C-4 substitution via a syn-S(N)2 mechanism. One application of the reaction of secondary amines with allylic cyclohexene epoxides, to give trans-1,2-aminoalcohols, is in the synthesis of the anticholinergic drug vesamicol, via an S(N)2 mechanism. Copyright (c) 2013 John Wiley & Sons, Ltd.

Gas-Phase Nucleophilic and Elimination Reactions in Simple Alkyl Nitrates

There has been increasing interest in the gas-phase reactivity of alkyl nitrates because of their well-known applications as explosives and because of then role in atmospheric and in marine processes This manuscript describes an experimental study by FT-ICR techniques of the gas-phase reactions of OH(-) and F(-) with methyl and ethyl Innate For methyl nitrate, the main reaction channel is found to be an elimination process promoted by abstraction of an a proton from the methyl group. Nucleophilic displacement of nitrate anion through an S(N)2 process at the carbon center Is also found to he an important reaction channel with methyl nitrate In ethyl nitrate, Ruination of NO(3)(-) is greatly enhanced and this is attributed to the ease of an E2-type elimination process promoted by proton abstraction at the beta position of the ethyl group. Theoretical calculations at the MP2/6-311+G(3df,2p)//MP2/6-31+G(d) level of theory ale consistent with the relative importance of the reaction channels and suggest that these reactions proceed through a double well potential The calculations also predict that nucleophilic attack by OH(-) at the nitrogen center (Sn2@N) is energetically the rueful ad pathway but experiments with (18)OH(-) showed no evidence for this channel. Single-point calculations reveal a strong preference for approach to the emboli center and may explain the lack of reactivity at the nitrogen center. Calculations were also carried out or NH(2)(-) and SH(-) to establish the reactivity pattern to provide a better understanding of environmentally relevant nitrate esters.

Neurophysiological patterns of ulnar nerve neuropathy in leprosy reactions

Background: Leprosy neuropathy, despite being primarily demyelinating, frequently leads to axonal loss. Neurophysiological examination of the nerves during Type 1 (T1R) and Type 2 reactions (T2R) may give some insight into the pathophysiological mechanisms.Methods: Neurophysiological examinations were performed in 28 ulnar nerves during a clinical trial of steroid treatment effectiveness, 19 patients with T1R and nine with T2R. The nerves were monitored during a period of 6 months; there were eight assessments per nerve, for a total of 224 assessments. Nine neurophysiological parameters were assessed at three sites of the ulnar nerve. The compound motor action potential amplitudes elicited at wrist, elbow and above, as well as the conduction velocity and temporal dispersion across the elbow, were chosen to focus on the changes occurring in the parameters at the elbow tunnel.Results and Conclusion: Neurophysiological changes indicating axonal and demyelinating processes during both T1R and T2R were detected across the elbow. Changes in demyelination, i.e. a Conduction Block, as a primary event present during T2R, occurring as an acute phenomenon, were observed regularly; in T1R Temporal Dispersion, a subacute phenomenon, was seen. During treatment remyelination occurred after both types of reactions.

Sequential Methyl-Fluorine Exchange Reactions of Siloxide Ions in the Gas Phase

Air Force Office of Scientific Research (AFOSR)

Making sense of brain tumour: A qualitative investigation of personal and social processes of adjustment

This study investigated personal and social processes of adjustment at different stages of illness for individuals with brain tumour. A purposive sample of 18 participants with mixed tumour types (9 benign and 9 malignant) and 15 family caregivers was recruited from a neurosurgical practice and a brain tumour support service. In-depth semi-structured interviews focused on participants’ perceptions of their adjustment, including personal appraisals, coping and social support since their brain tumour diagnosis. Interview transcripts were analysed thematically using open, axial and selective coding techniques. The primary theme that emerged from the analysis entailed “key sense making appraisals”, which was closely related to the following secondary themes: (1) Interactions with those in the healthcare system, (2) reactions and support from the personal support network, and (3) a diversity of coping efforts. Adjustment to brain tumour involved a series of appraisals about the illness that were influenced by interactions with those in the healthcare system, reactions and support from people in their support network, and personal coping efforts. Overall, the findings indicate that adjustment to brain tumour is highly individualistic; however, some common personal and social processes are evident in how people make sense of and adapt to the illness over time. A preliminary framework of adjustment based on the present findings and its clinical relevance are discussed. In particular, it is important for health professionals to seek to understand and support individuals’ sense-making processes following diagnosis of brain tumour.

NO reduction and CO oxidation over Cu/Ce/Mg/Al mixed oxide catalyst in FCC operation

Simultaneous NO reduction and CO oxidation in the presence of O-2,H2O and SO2 over Cu/Mg/AUO (Cu-cat), Ce/Mg/Al/O (Ce-cat) and Cu/Ce/Mg/Al/O (CuCe-cat) were studied. At low temperatures (<340 degreesC), the presence of O-2 or H2O enhanced the activity of CuCe-cat for NO and CO conversions, but significantly suppressed the activity of Cu-cat and Ce-cat, At high temperature (720 degreesC), the presence of O-2 or H2O had no adverse effect on the NO and CO conversions over these catalysts. The addition of SO2 to NO + CO + O-2 + H2O system had no effect on the, reaction of CO + O-2 over Cu-cat, but deactivated this catalyst for NO + CO and CO + H2O reactions; over Ce-cat, all of these reactions of NO + CO, CO + O-2 and CO + H2O were suppressed significantly; over CuCe-cat, NO + CO and CO + O-2 reactions were not affected while the reaction of CO + H2O was slightly inhibited. (C) 2002 Elsevier Science B.V. All rights reserved.

Improved description of chemical barriers with generalized gradient approximations (GGAs) and meta-GGAs

The performance of exchange and correlation (xc) functionals of the generalized gradient approximation (GGA) type and of the meta-GGA type in the calculation of chemical reactions is related to topological features of the electron density which, in turn, are connected to the orbital structure of chemical bonds within the Kohn-Sham (KS) theory. Seventeen GGA and meta-GGA xc functionals are assessed for 15 hydrogen abstraction reactions and 3 symmetrical S(N)2 reactions. Systems that are problematic for standard GGAs characteristically have enhanced values of the dimensionless gradient argument s(sigma)(2) with local maxima in the bonding region. The origin of this topological feature is the occupation of valence KS orbitals with an antibonding or essentially nonbonding character. The local enhancement of s(sigma)(2) yields too negative exchange-correlation energies with standard GGAs for the transition state of the S(N)2 reaction, which leads to the reduced calculated reaction barriers. The unwarranted localization of the effective xc hole of the standard GGAs, i.e., the nondynamical correlation that is built into them but is spurious in this case, wields its effect by their s(sigma)(2) dependence. Barriers are improved for xc functionals with the exchange functional OPTX as x component, which has a modified dependence on s(sigma)(2). Standard GGAs also underestimate the barriers for the hydrogen abstraction reactions. In this case the barriers are improved by correlation functionals, such as the Laplacian-dependent (LAP3) functional, which has a modified dependence on the Coulomb correlation of the opposite- and like-spin electrons. The best overall performance is established for the combination OLAP3 of OPTX and LAP3.

On the Nucleophilicity of Boryllithium Compounds. A Theoretical Study

Boron compounds are widely used in synthetic chemistry. The synthesis of the compounds is relatively easy, presenting thermodynamic stability and synthetic versatility. Almost all of them show electrophilic reactivity. Recently, some boryllithium species have been reported as a base or a nucleophile in reaction with organic electrophiles in S(N)2 reactions. In the present work, the proton affinity (PA) of boryllithium compounds was calculated. These values can be useful as theoretical reference values and to provide valuable complementary information for the interpretation and discussion of the basicity of these compounds. The proton affinity was calculated using a theoretical method based on density functional theory and high-level theoretical methods through MP2 and G2MP2 levels of theory. In addition, some global and local reactivity indexes based on density functional theory (DFT) on boryllithium compounds were studied. In order to compare and discuss the chemical reactivity of these compounds, some analogues and electrophilic boron compounds were also studied. Our results showed a local and global nucleophilic reactivity of the boryllithium molecules in agreement with the experimental. reactivity. The boryllithium compounds revealed to be strong bases in comparison to other analogue compounds studied in this work.

A quantum chemical study on the formation of phosphorus mononitride

The chemical mechanism of the (1)PN formation was successfully studied by using the CCSD(T)/6-311++G(3df,3pd) level of theory. The (1)NH(3) + (3)PH and (4)P + NH(3) reaction paths are not energetically favorable to form the (1)PN molecule. However, the (3)NH + (3)PH, (4)N + (3)PH(3), (4)N + (3)PH, (4)P + (3)NH, and (4)P + (2)NH(2) reaction paths to form the (1)PN molecule are only energetically favorable by taking place through specific transition states to form the (1)PN molecule. The NH(3) + (3)PH, (4)N + (1)PH(3), NH(3) + (4)P, and (4)N + (2)PH(2) reactions are spin-forbidden and the probability of hopping for these reactions was estimated to be 0 by the Landau-Zener theory. This is the first detailed study on the chemical mechanism for the (1)PN formation. (C) 2009 Elsevier B.V. All rights reserved.