Nucleophilicity Hammett correlation

Electronic effects. Nucleophilic attack is favoured by electron-withdrawing groups on the amide and the acyloxyl side chains. Interpolated bimolecular rate constants at 308 K for the series of para-substituted /V-acetoxy-/V-butoxybenzamides 25c, 26b-g and 26i (Table 5) gave a weak but positive Hammett correlation with a constants ip = 0.13, r = 0.86).42,43 These Sn2 reactions are analogous to those of aniline and substituted pyridines with phenacyl bromides, which have similar Arrhenius activation energies and entropies of activation in methanol (EA= 14-16 kcal mol-1, AS = — 27 to —31 calK-1 mol-1) and 4-substituted phenacyl halides afforded a similar Hammett correlation with pyridine in methanol (cr, p — 0.25).175... 

Nucleophilic substitution reactions are among the most widely studied reactions in chemistry (1). This is due, in part, to their synthetic utility, to the wide range of substrates and reactants, and to their relatively clean kinetic behavior. In contrast to thermodynamically based studies of structure and reactivity (e.g., Hammett correlations of acidity), a satisfactory understanding of kinetic reactivity in S 2 reactions has yet to be achieved, albeit not for lack of talent or effort expended. 

Nucleophilic attack by iV-methylaniline is favoured by electron-withdrawing groups on the amide and acyloxyl side chains. A series of / ara-substituted Af-acetoxy-Af-butoxy-benzamides (138) (Table 6) gave a weak but positive Hammett correlation with a constants (p = 0.13, r = 0.86) °. The analogous reactions of pyridine with para-substituted phenacyl halides in methanol afforded a similar Hammett correlation a, p = 0.25) . The bimolecular rate constants for the limited series of Ai-benzoyloxy-A-benzyloxybenzamides (139) in Table 6 correlated strongly with Hammett a constants (p = 1.7, r = 0.97) °. Stabilization of developing carboxylate character supported the computed charge redistribution in the transition state ... 

The importance of both electronic and steric factors is borne out by the reactions of piperidine in equation (159) at 30 °C in benzene (k, m" s" ) PhCOC=CPh (4-4), PhCOC=CBu-rt (1-9), PhCOC=CBu-/ (0 012), MeCOC=CPh (M5)i . If the steric requirements are made constant, as in a series of anilines in process (159) in 95% ethanol, the resulting rate data yield a satisfactory Bronsted plot and Hammett correlations /3 0-93 and p = —(212 to 2-18) in the range 20-50 °C . Further structure-reactivity variations were made with morpholine as nucleophile and XC6H4CSCCOC6H4Y as electrophile in 95% ethanol, the Hammett p = 1-13 to 0-97 for the X series and F42 to 1-20 for the Y series from 20-50 in r-BuOH at... 

Kinetics demonstrate that in the epoxidation of the n-hexyl jS-alkylvinyl ketones 54 the possibility of nucleophilic attack decreases as the carbon chain in group R becomes longer or more branched. The Hammett correlation has been studied in the reaction of 55. ... 

From the results summarized in Table I, apparently the Brpnsted relationship will hold for all combinations of nucleophiles and electrophiles. Because, as pointed out previously, the Hammett equation is really a special case of the Brpnsted relationship, all the legion of nucleophile-electrophile, rate-equilibrium Hammett correlations that have been studied also fall under the scope of the Brpnsted relationship. For example, nucleophilicities of ArO , ArS , ArC(CN)2 , and the other families listed in footnote c of Table I have generally been correlated by the Hammett equation, where the acidities of benzoic acids in water are used as a model for substituent interactions with the reaction site (a), and the variable parameter p is used to define the sensitivity of the rate constants to these substituent effects. The Brpnsted equation (equation 3) offers a much more precise relationship of the same kind, because this equation does not depend on an arbitrary model and allows rate and equilibrium constants to be measured in the same solvent. Furthermore, the Brpnsted relationship is also applicable to families of aliphatic bases such as carboxylate ions (GCH2C02 ), alkoxide ions (GCH20 ), and amines (GCH2NH2). In addition, other correlations of a kinetic parameter (log fc, AGf, Ea, etc.) can be included with various thermodynamic parameters (pKfl, AG°, Eox, etc.) under the Brpnsted label. 

In Table 19, the relative rates, obtained in the alkylation of 3-substituted pyridines by f-butyl radical, are reported. The exceptional positional selectivity (only the position 6 is attacked) results from combined polar and steric effects. A satisfying Hammett correlation was observed with Op the value of p = 5.5 is of the same order of magnitude of those of nucleophilic aromatic substitutions, indicating a high degree of charge development in the transition state. 

That would explain the fact that in nucleophilic substitutions the Hammett correlations fit better with [Pg.35]

It is a broken Hammett plot, in which the minimum occurs with styrene itself i.e., where the substituent, H, is the minimum on the electron-donation/ electron-withdrawal scale). Broken Hammett correlations are traditionally interpreted to signify a change in reaction mechanism as a function of changes in the substituents electronic properties. Here, the change in mechanism mirrors the ambiphilicity of PhOCCl the carbene behaves as an electrophile toward electron-rich styrenes, but as a nucleophile toward electron-poor styrenes. Very similar behavior toward styrenes is revealed by MeOCCl, [52] also known to be an ambiphile on the basis of its behavior toward other alkenes (see above, and Table 2). 

Rate data for the ozonolysis of a series of substituted styrenes in CCI4 at 25°C are summarized in Table 6.14. Do the data show a linear Hammett correlation with either tr, cr, or meta substituents in all three correlations.) If so, what is the value of p at 25°C What do these results suggest about the reaction mechanism Specifically, does the addition of ozone appear to be electrophilic or nucleophilic in nature ... 

The in situ formation of Pd(0) complexes takes place when Pd(OAc)2 is associated with various phosphines (i) aromatic phosphines (p-Z—C6H4)3P (Z = EDG or EWG). The formation of the Pd(0) complex follows a Hammett correlation with a positive slope [20]. The more electron-deficient the phosphine, the faster the reduction process this is in agreement with the intramolecular nucleophilic attack of the acetate onto the ligated phosphine as proposed in Scheme 1.13 (ii) aliphatic phosphines [20] (iii) water-soluble phosphines, triphenylphosphine trisulfonate (trisodium salt) [25] and triphenylphosphinetricarboxylate (trilithium salt) [26]. One major exception is the tri-o-tolylphosphine P(o-Tol)3, which cannot reduce Pd(OAc)2 to a Pd(0) complex in DMF or THE. Instead, an activation of one C-H bond of the tolyl moieties by Pd(OAc)2 takes place, leading to a dimeric P,C-palladacycle (see Section 1.5), as reported by Herrmann et al. in 1995 [27]. Such a Pd(ll) P,C-palladacycle catalyses Mizoroki-Heck reactions [27]. It is, however, a reservoir of a Pd(0) complex, as recently established by d Orly6 and Jutand [28] in 2005 (see Section 1.5). 

Special features of the interaction of pyridine, quinoline, and related compounds with triphenylphosphine have been reported." The mechanism of sulfurization of substituted triphenylphosphines with 4-(3- and 4-substituted)-l,2,4-dithiazolidine-3,5-diones in acetonitrile, dichloromethane, tetrahydrofuran, and toluene at 25 C has been studied." The reaction pathway involves rate-limiting initial nucleophilic attack of the phosphorus at sulfur followed by fast decomposition of the phosphonium intermediate to the corresponding phosphine sulfide, phenylisocyanate, and carbonylsulfide. From the Hammett correlations and solvent dependency, it was concluded that the transition-state structure is very polar and resembles the zwitter-ionic intermediate. 

The nucleophilic reactivity of 2-halogenothiazoles is strongly affected by the substituent effect, depending on the kind of substitution reaction. Positions 4 and 5 can be considered as meta and para , respectively, with regard to carbon 2 and to groups linked to it consequently, it is possible to correlate the reactivity data with Hammett s relationships. 

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