Calculated nucleophilic reactions

Figure 4. Calculated nucleophilic reactions with MeO. Adaptedfrom reference 26.

Qualitative models of reactivity and quantum mechanical calculations of reaction paths both indicate an angular approach of the attacking nucleophile to the first-row sp -hybridized electrophilic centers M at intermediate and reactive distances, 29. The geometry of 29 is also characteristic for the case of nucleophilic addition to electron-deficient centers of main-group 12 and 13 elements. By contrast, a linear arrangement 30 of making and breaking bonds is required for sp -hybridized first-row centers (C, N, O)... 

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

FIGURE 13.3 Comparison between calculated nucleophilicity (to-, in eV) and experimental efficiency (nucleophilicity measure) for anions in the X- + CH3C1 reaction. (Reprinted from Jaramillo, P., Perez, P., Contreras, R., Tiznado, W., and Fuentealba, P., J. Phys. Chem. A, 110, 8181, 2006. With permission.)... 

Calculations of the nucleophilic reactions with MeO" were performed for the carbocations 4H+, 5H+ and 6H+ in order to simulate the crucial step of aza-PAH/adduct formation. These reactions were considered as models for evaluation of the reactivity trend for these carbocations toward nucleophiles. Thus, the thermodynamical tendency of each carbocation to react with the nucleophilic sites of DNA was estimated. 

As shown in Fig. 1, the big lobes of these hybrids point toward each other. Therefore, if the nucleophile approaches the substrate from the front side, its HOMO overlaps in phase with the big lobe of 0c and out-of-phase with the big lobe of 0x-Numerical calculations show that the unfavourable (nucleophile-leaving group) interaction usually overrides the favourable (nucleophile - reaction center) interaction in this front-side approach, so that back-side attack is finally preferred, leading to inversion of configuration. 

Nucleophilic reaction of Et3N with diallyl disulfide has been found to differ from that with diallyl sulfide in being very much more exothermic and also autocatalytic.14 Possible mechanisms were discussed. EHMO calculations have been performed for... 

Richard has also shown that intrinsic barriers for carbocation reactions depend not only on the extent of charge delocalization but to what atoms the charge is delocalized. In a case where values of pifR for calculation of A were not available, comparisons of rate constants for attack of water kH2o with equilibrium constants for nucleophilic reaction with azide ion pKAz for 65-67 showed qualitatively that delocalization to an oxygen atom leads to a lower barrier than to an azido group which is in turn lower than to a methoxyphenyl substituent.226... 

Calculations of reactions of simple nucleophiles such as H with carbonyl compounds show that, in the gas phase, there is no barrier. Activation energies in solution arise from desolvation of the nucleophile. However, reactions of a nucleophile with an alkene or an alkyne do have a barrier in the gas phase. 

In a quantitative theory we shall also have to calculate the energy difference between the normal state and the activated state in which on the reacting atom is localized either a pair of electrons (electrophilic reaction SE), a sextet (pos. charge, nucleophilic reaction SN), or a single electron (radical reaction SR) or in which a pair of electrons is localized in a certain bond (true double bond reactions). The remaining possibilities for resonance will determine mainly which of the possible activated states will have the lowest energy and thus what course the reaction will take (localization hypotheses). 

Although few applications of these very recently implemented models have yet appeared, some calculations for free energies of transfer into aqueous solution are available.Polarization of the solute has been analyzed by reference to the molecular dipole moment,including comparison to a hybrid quantum mechanics/molecular mechanics approach,and the effect of aqueous solvation on conformational equilibria and simple nucleophilic reactions has been examined.] jo consideration of CDS solvation terms in conjunction with these models has appeared. 

These results are interpreted in terms of alternative reaction mechanisms. The reaction of less bulky ketene silyl acetals is initiated by electron transfer from these compounds to a Lewis acid (Sch. 2). Bulkier ketene silyl acetals, on the other hand, undergo a ubiquitous nucleophilic reaction. Such a mechanistic change is discussed on the basis of a variety of experimental results and on semi-empirical PM3 MO calculations. 

Quantum mechanical calculations show that the sdyl cation (19) has a twisted structure, and that the a-COj group provides substantial electrostatic stabilization. Isotope effects for its formation reaction are also reported. Evidence is provided for the stabilization of incipient oxocarbenium ions by axial electronegative substituents, as in (20) the presence of the most electronegative substituent results in the fastest reaction. Lewis acid-promoted cleavage of spirocyclic dioxanes such as (21) involves oxonium ions, and high axial vs equatorial product selectivities are possible with the correct choice of Lewis acid and nucleophile. Reactions which lead to 1,3-dioxenium salts have been reviewed. ... 

The molecular formula of 7-10 indicates that trichloroacetonitrile has reacted with the starting material. By using Hint 1.2, three rings and/or ir bonds are calculated. Because the starting alcohol has two rr bonds and the nitrile has two n bonds, a nucleophilic reaction with the nitrile is likely. Potassium hydride should remove the most acidic proton from the starting alcohol, the proton on the oxygen. 

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