Electrophilicity and nucleophilicity parameters

Scheme 53 Electrophilicity and nucleophilicity parameters according to Eq. (23). (From Ref. 182, reprinted with permission of VCH Verlagsgesellschaft.)...

Ionization rate constants in aqueous acetonitrile were obtained for trityl chlorides, bromides, and acetates covering 21 units in the pA1r+ of the trityl cation. This study observed solvolyses with and without common ion return, solvolyses where the trityl cation could be observed to form and then decay, solvolyses where water addition occurs before complete formation of the cation, and at the other extreme, solvolyses that yield persistent carbocations. Mayr and coworkers showed how electrophilicity and nucleophilicity parameters rationalize reactivity patterns and resolve mechanistic controversies in organocatalytic cyclizations. The thermodynamic affinities of a large number of Lewis bases were computed for addition to the methyl, diphenylmethyl, and triphenyl-methyl cations. ... 

Correlation analysis of solvent effects on the heterolysis of p-methoxyneophyl tosyl-ate has been performed by using the Koppel-Palm and Kamlet-Taft equations. The reaction rate is satisfactorily described by the electrophilicity and polarity parameters of solvents, but a possible role for polarizability or nucleophilicity parameters was also examined. 

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. 

The Swain Equation (34) provides very accurate predictive power for a limited range of solvents and processes based on a statistical analysis of a five-parameter equation. The origins of the Swain parameters are not explicit, although the acity (A) and basity (B) coefficients are related to electrophilic and nucleophilic processes respectively. Many fundamental processes have been implicated in solvent effects and the equation of Koppel and Palm (Equation 37) incorporates the major factors thought to be involved. 

The propensity for C-N vs. N-H activation correlates well with substituent Hammet parameters groups that increase the basicity of aniline increase the relative rate of N-H activation, suggesting that nucleophilic attack by the amine at an empty d /dy orbital of Ta(silox)3 preceeds oxidative addition. On the other hand, electron-withdrawing substituents decrease the rate of N-H activation and increase the rate of C-N activation, similarly to the effects observed on electrophilic aromatic substitution. Nucleophilic attack by the filled d a orbital of Ta(silox)3 is expected to occur at the arylamine ipso carbon preceding C-N oxidative addition. The carbon-heteroatom cleavages can be accomodated by mechanisms using both electrophilic and nucleophilic sites on the metal center. 

The results with dimethoxyearbene highlight an inherent deficiency of Eq. 4 it is an empirical correlation of parameters normalized to the electrophilic car-bene, CCI2. Its electrophilic heritage means that although the equation can predict values for highly resonance stabilized, nucleophilic carbenes such as (MeO)2C or Me2NCOMe, these are virtual selectivity indexes. The nucleophilic carbenes simply do not add to the aUcenes of the standard set. However, the equation helps us define the Wcxy regions in which electrophilic and nucleophilic carbenes reside. The electrophilic species, which react appropriately with the standard alkenes of Table 1, exhibit w xy values between 0.29 (BrCCOOEt) and... 

For the special interest of the method which it uses to evaluate the necessary parameters, through the use of Hammett substituent constants (p. 156), the work of Jaffe on pyridine and pyridine 1-oxide should be mentioned. Considering both orientation and activation, it is about as successful overall in dealing with electrophilic and nucleophilic substitution in these compounds as are the studies already discussed. 

Table 19.3 illustrates the local parameters in terms of MPA. The Zn-center in all the conformers bears a negative charge and hence is good for attack by an electrophile. However, the Be-centers show a diverse trend in atomic charges and thus prone to both electrophilic and nucleophilic attacks. No precise insight into the reactivity pattern of these Be-Zn bimetallic conformers can be gained from the local descriptors. 

Nucleophile and electrophile combinations are reported to follow Eq. (26.1) [5], where electrophiles are characterized by one parameter (electrophilicity ) and nucleophiles are characterized by two parameters (slope Sn and nucleophilic-ity N) ... 

It is accepted that the acmal nucleophile in the reactions of oximes with OPs is the oximate anion, Pyr+-CH=N-0 , and the availability of the unshared electrons on the a-N neighboring atom enhances reactions that involve nucleophilic displacements at tetravalent OP compounds (known also as the a-effect). In view of the fact that the concentration of the oximate ion depends on the oxime s pATa and on the reaction pH, and since the pKs also reflects the affinity of the oximate ion for the electrophile, such as tetra valent OP, the theoretical relationship between the pATa and the nucleophilicity parameter was analyzed by Wilson and Froede . They proposed that for each type of OP, at a given pH, there is an optimum pK value of an oxime nucleophile that will provide a maximal reaction rate. The dissociation constants of potent reactivators, such as 38-43 (with pA a values of 7.0-8.5), are close to this optimum pK, and can be calculated, at pH = 7.4, from pKg = — log[l//3 — 1] -h 7.4, where is the OP electrophile susceptibility factor, known as the Brpnsted coefficient. If the above relationship holds also for the reactivation kinetics of the tetravalent OP-AChE conjugate (see equation 20), it would be important to estimate the magnitude of the effect of changes in oxime pX a on the rate of reactivation, and to address two questions (a) How do changes in the dissociation constants of oximes affect the rate of reactivation (b) What is the impact of the /3 value, that ranges from 0.1 to 0.9 for the various OPs, on the relationship between the pKg, and the rate of reactivation To this end, Table 3 summarizes some theoretical calculations for the pK. ... 

Nitrosyl complexes, in which Vno > 1886 cm or Fnq > 13.8 mdyn/A, usually react as electrophilic nitrosating agents so that the ligand can be considered NO [26]. Nucleophilic attack on the nitrosyl nitrogen is a common reaction encountered in the chemistry of nitroprusside and the rates and activation parameters for a number of different nucleophiles are listed in Table 3. Hydr-oxylamine adducts to nitroprusside via a rate law that is first order in the complex, the ligand and hydroxide (k = 4.5 x 10 M s ). 

Dinitrobenzofuroxan (DNBF) is known as a superelectrophile due to its high reactivity both as an electrophile and in its pericyclic addition reactions. NMR studies show that reaction with 2-aminothiazole and its 4-methyl derivative yield anionic carbon-bonded adducts such as (11) by reaction at the 5-position, whereas the 4,5-dimethyl derivative reacts via the exocyclic amino group. Kinetic studies of the first two compounds, both in acetonitrile and in 70 30 (v/v) water-DMSO, have been used to assess their carbon nucleophilicities and place them on the Mayr nucleophilicity scale.55 In a related study, the nucleophilic reactivity, in acetonitrile, of a series of indoles with both DNBF and with benzhydryl cations have been compared and used to determine nucleophilicity parameters for the indoles.56... 

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