Nucleophilic reactivity contributing factors

IV-acyloxy-iV-alkoxyamides, biological activity, 97-115 anticancer activity of, 115 mutagenicity of, in Ames Salmonella/ microsome assay, 97-115 IV-acyloxy-iV-alkoxyamides, chemical reactivity, 59-96 factors contributing, 59-60 nucleophilic substitution reactions, see Nucleophilic substitution reactions solvolysis studies, see Solvolysis... 

One of the factors directing the alkylation of an enolate is the Jt-facial selectivity. The differences in reactivity of the two diastereotopic faces of the enolate, due to steric and electronic features, contribute to the steric control of the alkylation (for extensive reviews, see refs 1, 4, and 30). Likewise, stereoelectronic features are important control elements for C- versus O-alkylation, as illustrated by the cyclization of enolates 1 and 3 via intramolecular nucleophilic substitution 39. 

L in Scheme 11.3) departs. Nucleophilic addition to the intermediate benzyne (step D) is readily explained by perturbative MO arguments. The extra and orbitals of benzyne are compared to those of ethylene in Figure 11.7. The aromatic n system is not involved in the special properties of benzyne. The third benzyne n bond is due to the overlap in fashion of the two sp2 hybrid orbitals which lie in the nodal plane of the intact 6 electron system. Two factors contribute to a very low LUMO for benzyne. First, the sp2 hybrid orbitals are lower in energy than the 2p orbitals from which the ethylene orbitals are constructed. Second, the intrinsic interaction between the two sp2 orbitals is less than the normal / cc since the orbitals have less p character and are tipped away from each other. The low LUMO of benzyne makes the molecule a strong Lewis acid, susceptible to attack by bases, and a reactive dienophile in Diels-Alder reactions, as we shall see later. 

One factor that contributes to the heterogeneous nature of polypeptides produced by NCA polymerization is the multiple reactivity of the monomers [9]. NCA contain four reactive sites two electrophilic carbonyl carbons and two nucleophilic centers after deprotonation of the a-CH and NH hydrogen atoms. By use of traditional nucleophilic or basic initiators NCA ring-opening polymerization can proceed simultaneously along different competing pathways, which broadens mo-... 

Another factor that contributes to the high level of toxicity of the organophosphates is the stability of the phosphate ester bond formed with the enzyme The enzyme does not spontaneously hydrolyse itself, not even slowly as is the case with the carbamates. Reactivation can be accomplished with an extraneous nucleophile such as hydroxy-lamine (Figure 9.18). While the latter works fine in vitro, it is too toxic for use in vivo. However, analogs such as prali-... 

Details about ILs properties are covered in this book in the contributions by Seddon, Chiappe and Scott. However, two features deserve a comment for their possible consequences on reactivity and catalysis. First, depending on a delicate balance of entropie and enthalpic factors, including the polarity of the transition state structures with respect to regents, a reaction can be either speeded up or decelerated when carried out in an ionic liquid medium compared to a molecular solvent. An elegant study by Welton shows that in S-,2 reactions, primary, secondary and tertiary amines are more reactive as nucleophiles in ionic liquids, while halides react faster in conventional molecular solvents such as CH2CI2. In particular in a series of [Bmim] salts the order of nucleophilicity of halides is determined by the anion partner. To the same direction moves a kinetic study by Dyson on a cationic Ru(II) complex-catalysed hydrogenation of styrene in ILs, where it is clearly demonstrated that both the cation and the anion of the IL can inhibit or accelerate the formation of the active catalytic species. ... 

A similar conclusion had been obtained earlier by Letai r and Savereide for the solvolysis of several anionic dienyl esters catalyzed by poly-4-vinylp5aidine 7 in 50% ethanol-water (5/). It is noteworthy that a rate maximum is again observed with three-quarters of the pyridine group in the neutral form. A complicating factor in quantitatively estimating the electrostatic contribution is that the reactivity of a ven nucleophilic group may vary with the degree of protonation. This problem will be discussed later in connection with the catalytic action of vinylimidazole copolymers. 

---