Electrophilicity parameters

An HSAB analysis of singlet carbene reactivity based on B3LYP/6-31G computations has calculated the extent of charge transfer for substituted alkenes,122 and the results are summarized in Figure 10.3 The trends are as anticipated for changes in structure of both the carbene and alkene. The charge transfer interactions are consistent with HOMO-LUMO interactions between the carbene and alkene. Similarly, a correlation was found for the global electrophilicity parameter, co, and the ANmax parameters (see Topic 1.5, Part A for definition of these DFT-based parameters).123... 

Rate constants have been determined for the reaction of four iminium ions (Me2S=CH2, Pri,N=CH2. Ph(Me)N=CH2, and Mc2N=CHC1) with a range of nucleophiles.44 The results allow calculation of electrophilicity parameters for these ions, helping to predict whether a particular aminomethylation reaction is likely to work. 

The +C(SH)3 cation and the radical dication derived from it have been the subject of high-level calculations.67 The ability of two adjacent sulfur atoms to stabilize cations, anions, and radicals makes these species usefiil for relating bond-breaking and electron-transfer energies.68,69 Electrophilicity parameters for the dithiocarbenium ions (27) have been worked out,70 and the stabilities of the cations (28), (29) and (30) have been estimated using PM3 calculations.71 Cation (31) can be captured by solvent or azide ion, or it may ring close to (32), which subsequently alkylates another (31) cation as shown.72... 

In principle, these measurements represent an application of the Swain-Scott relationship to two nucleophiles only. This is apparent from Equation (28), in which nAz corresponds to n for the azide ion and the electrophilic parameter s is seen to measure the selectivity of the carbocation between azide... 

Mayr initially defined a set of electrophilic parameters for the benzhydryl cations using a reference nucleophile, which was chosen as 2-methyl-1-pentene.268,269 Values of E were then defined as log k/k0, where k0 refers to a reference electrophile (E= 0), which was taken as the 4,4 -dimethoxybenzhydryl cation. Plots of log k against E for other alkenes are thus analogous to the plots of logk against p fR in Fig. 7 except that the correlation is referenced to kinetic rather than equilibrium measurements. However, they differ from plots based on the Swain-Scott or Ritchie relationships in which log k is normally plotted against a nucleophilic parameter, that is, n or N+, rather than E. 

One way to modify Equation (31) to allow for the different slopes is to multiply the electrophilicity parameter E by a variable 5 as shown in Equation... 

Note again that 5 here differs from s in the Swain-Scott equation which refers to the slope of a plot of log k versus the nucleophilicity parameter n (or N) rather than electrophilicity parameter (E). 

Picosecond absorption spectroscopy was employed to study the dynamics of contact ion pairs produced upon the photolysis of substituted diphenylmethyl acetates in the solvents acetonitrile, dimethyl sulfoxide, and 2,2,2-trifluoroethanol.66 A review appeared of the equation developed by Mayr and co-workers log k = s(N + E), where k is the rate constant at 20 °C, s and N are nucleophile-dependent parameters, and is an electrophilicity parameter 67 This equation, originally developed for benzhydrylium ions and n-nucleophiles, has now been employed for a large number of different types of electrophiles and nucleophiles. The E, N, and s parameters now available can be used to predict the rates of a large number of polar organic reactions. Rate constants for the reactions of benzhydrylium ions with halide ions were obtained... 

Mayr and Patz have recently evaluated 56 reaction series, mostly for reactions as described in this article, and derived Eq. (23), in which carbo-cations are characterized by the electrophilicity parameter E, whereas nucleophiles are characterized by the nucleophilicity parameter N and the slope parameter s [182]. The latter quantity, s, which basically describes the slopes of plots as shown in Figs. 10 and 11, ranges from 0.8 to 1.2 for 91 % of the 7r-nucIeophiles investigated. The mathematical form of Eq. (23) implies that the exact value of s will usually only be of importance when rate constants, which strongly deviate from 1 (e.g., (log > 5), are considered. Some of the characterized nucleophiles and electrophiles are listed in Scheme 53, where the two scales are arranged in such a way that electrophiles and nucleophiles which are located at the same level are predicted to combine with rate constants of lg k = -5 s. With s 1 one expects slow combinations for electrophile-nucleophile pairs at the same level, whereas reactions of nucleophiles with electrophiles located below them are expected to be very slow or not to occur at all at 20° C. 

Recent works of Mayr and co-workers4-14 have illustrated this trend. In fact, these authors have established, in contrast to the accepted opinion about the relative character of the experimental electrophilicity/nucleophilicity scales for many reactions in organic and organometallic chemistry, that it would be possible to define nucleophilicity and electrophilicity parameters that are independent of the reaction partners. Mayr et al. proposed that the rates of reactions of carbocations with uncharged nucleophiles obey the linear free energy relationship given by 4-14... 

Figure 6 Plot of experimental electrophilic parameter E vs the electrophilicity index to for the benzylidenemalononitriles series. ( ) Predicted value. Rate coefficients k from reference 123...

Domingo investigated the global electrophilic parameter, w, as an indicator of relative reactivity. Table 10.9 gives the value of this parameter calculated for a number of dienes and dienophiles. 

A large data set on the electrophility parameter (Reichardt parameter ) for binary water-non-water mixed solvents was compiled. ... 

Figure 14 Correlation between the electrophilicity parameter and substituent constants for 2-methoxy-3-X-5-nitrothiophene. Reproduced with permission from (2014iJCK(46)470). Copyright 2006 John Wiiey and Sons.

Electrophilicity parameters, E, have been measured for a range of aliphatic and aromatic aldehydes, Al-acceptor-substituted araldimines, and a,/S-unsaturated ketones, based on rates of several reaction classes measured spectrophotometricaUy in DMSO. ... 

Nucleophilicity parameters, N and % for electrophile-nucleophile combination based on the Mayr equation ogk = Sj (N+E), were reported for highly nucleophilic pyridines bearing amino groups at carbons 3, 4, and 5, isothioureas," and thiocarboxylates, dithiocarbamate, and dithiocarbonate." Electrophilicity parameters E were reported for triarylmethyl cations with para and meta fluorine substituents," 1,3-diarylallyl cations," and aldehydes, imines, and enones." Nucleofugality parameters Nf and Sf for ionization based upon the Mayr equation logki = Sf(Ef + Nf) were reported for acetate in aqueous methanol" and chloride in aprotic solvents." The latter study also shows that common solvent parameters do not reliably predict ionization rates in aprotic solvents. Electrofugality parameters Ef were reported for triarylmethyl cations with para and meta fluorine substituents." ... 

A DFT study addressed the relationship between electrophilicity and electro-fugality. A number of descriptors obtained by semi-empirical and DFT methods were evaluated for estimations of the Mayr electrophilicity parameters. For a set of 64 electrophiles, good correlations were found using reactivity descriptors calculated by the PM6 semi-empirical and DFT methods. Rate constants for reactions of amines and benzhydrylium ions were calculated using various theoretical methods. A combined ONIOM/DFT approach gave good agreement with experiment. 

The Mayrgronp has apphed Equation 1.4 to determine the electrophilicity parameters [19b], E, in reactions between electrophiles and nncleophUes, where N is the... 

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