Nucleophilic constant coefficients

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. ... 

Numerical values of k and K, the equilibrium constant for Co(CN)5X 3 formation, have been assembled in Table IV. In the three cases where temperature coefficient data is available, it can be seen that the relative values of k4 are determined by the differences in both AH and AS. A comparison of k and K indicates that an increase in K is accompanied by a decrease in k. For any given nucleophile 4 and K may be related by the expression K = k kz/kzki. This latter expression has been used to calculate the numerical values of K for the SCN fcnd N3" systems where equilibrium data is not available. 

In this connection, it is helpful to look first at the reactivity of the anions. There is no generally acceptable measure of nucleophilic reactivity since both the scale and order of relative reactivities depend on the electrophilic centre being attacked (Ritchie, 1972). However, in the present reaction, the similarity in the reactivity of the different anions is remarkable. Thus, the Swain and Scott n-values (cf. Hine, 1962) indicate that the iodide ion should be 100 times more reactive than the chloride ion in nucleophilic attack on methyl bromide in aqueous acetone. In the present reaction, the ratio of the rate coefficients for iodide ions and chloride ions is 1.4. This similarity led to the suggestion that these reactions are near the diffusion-controlled limit (Ridd, 1961). If, from the results in Table 5, we take this limit to correspond to a rate coefficient (eqn 19) of 2500 mol-2 s 1 dm6 then, from the value of ken for aqueous solutions at 0° (3.4 x 109 mol-1 s 1 dm3 Table 1), it follows that the equilibrium constant for the formation of the electrophile must be ca. 7.3 x 10 7 mol-1 dm3. This is very similar to the equilibrium constant reported for the formation of the nitrosonium ion (p. 19). The agreement is improved if allowance is made for the electrostatic enhancement of the diffusion-controlled reaction by a factor of ca. 3 (p. 8) the equilibrium constant for the electrophile then comes to be ca. 2.4 x 10-7. 

Conversely, the decrease in the rate constant for the hydroxide ion catalyzed reaction of l,l,l-trichloro-2-methyl-2-propanol in the presence of polyoxyethylene(23) dodecanol and polyoxyethylene sorbitan mono-decanoate has been rationalized by assuming that the nucleophilic reaction occurs only in the bulk solution and that a substantial fraction of the substrate is solubilized by the surfactant. The latter assumption was verified by measurements of the solubility of l,l,l-trichloro-2-methyl-2-propanol, and hence the distribution coefficients, in the micellar systems (Anderson and Slade, 1966). 

Arrhenius parameters (as far as available) for the ring-opening reactions of ethylene oxide, propylene oxide, and isobutylene oxide. Overall values of ftCi and fcHcl obtained for propylene oxide have been split into rate coefficients for attack at primary carbon and attack at secondary carbon, utilizing gas chromatographic product analysis data [152]. (It is interesting to note that the results for attack at primary carbon are of the same order of magnitude as the corresponding values for ethylene oxide.) First-order rate coefficients at a constant acid concentration for the acid catalyzed hydrolysis of various epoxides [153] are collected in Table 10. Rate coefficients of the uncatalyzed and acid catalyzed reactions of ethylene oxide with various nucleophiles [151, 154] can be found in Table 11. 

In these mechanisms, the overall rate coefficient depends on the equilibrium constant of carbonium ion formation as well as on the rate coefficient of nucleophilic attack on the carbonium ion. It can be expected that steric hindrance is relatively unimportant in the reaction of the carbonium ion with the nucleophile. Additional experiments will be necessary to supply confirming evidence for the suggested mechanism. 

Even so a Bronsted coefficient of 0.66 would account for the rate constant ratio. Both of these values fall within the range of Bronsted coefficients typically observed for general-acid catalysis. An acid with a pK of 6.9 is largely protonated at pH 5.1 and no corrections are required. From these considerations it is likely that the stereochemistry of the helix favors nucleophilic catalysis by the His residue with the highest number in the sequence and general-acid catalysis by the residue with the lowest number. 

A major contribution of Ritchie s has been his observation that a large number of nucleophiles show a constant selectivity toward a variety of electrophiles. In LFER terms, the reactivity of the nucleophile can be given by a single parameter with no selectivity coefficient (such as Brpnsted (5 or Swain-Scott s) (26b) ... 

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