Nucleophilic aliphatic relationships

An obvious difficulty arises with this rather elaborate rationale when phosphoramidate and aryl phosphoramidate monoanions are compared for example, the dissimilarity of the dioxan effect yet the identity of product distribution observed in methanol-water competition experiments. Preliminary studies in the author s laboratory have revealed striking differences in the hydrolytic behavior between a series of phosphoramidafes derived from primary aliphatic amines and the above aryl systems. No linear structure-reactivity relationship between the logarithmic rate of hydrolysis of the monoanion species and the pKa of the amine is observed19. Moreover, the rate of hydrolysis of phosphoramidate monoanions derived from aliphatic amines is at least 104 times slower than those formed from aryl amines. In contrast, only a thirtyfold decrease in rate is observed for the corresponding ApKa in the O-phos-phate monoester series. The suspicion that mechanism (1), even with the above proposed modification, is not an accurate description of phosphoramidate monoanion hydrolysis derives some further support from the observation that the monoanion is subject to nucleophilic attack by substituted pyridines al-... 

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. 

Additions of acetals and orthoesters to enol ethers probably represent the most intensively studied class of Lewis acid promoted reactions in the chemistry of aliphatic compounds. Since usually catalytic amounts of BFg OEta have been employed, concentration control (rule A) should predominate. Unlike the solvolyses of alkyl halides, the acid catalyzed hydrolyses of acetals and orthoesters do not follow a rate equilibrium relationship so that the corresponding hydrolysis rates cannot be used for the analysis of electrophilic addition reactions. We have, therefore, carried out competition experiments to determine relative reactivities of acetals and orthoesters towards methyl vinyl ether in presence of catalytic amounts of BF3 0Et2 (Figure 11). As the reactivity order towards other ir nucleophiles can be expected to be similar, the krei values of Figure 11 can be used to rationalize or predict the results of acetal and orthoester additions 1 1 Adducts can only be generated selectively if the k ei values of the designed products are smaller than the k Qi values of the reactants. 

An ACEM involving the sole activation of the alcohol by hydrogen bonding (and subsequently the activation of the hydroxyl polymer chain end) and favoring a nucleophilic attack on the monomer substrate by the active initiator was proposed (Scheme 26). The resulting aliphatic polyesters exhibited high reliability of the presence of end groups, narrow dispersities, and a linear relationship between conversion and molar mass. 

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