Nucleophilic reactivity influencing factors

Ambident nucleophilic reactivity is more intriguing and complex, as the reaction is influenced by numerous factors—countercation, electrophile, solvent, temperature, and the inherent structural characteristics of the nucleophile. The... 

Nucleophilic Trapping of Radical Cations. To investigate some of the properties of Mh radical cations these intermediates have been generated in two one-electron oxidant systems. The first contains iodine as oxidant and pyridine as nucleophile and solvent (8-10), while the second contains Mn(0Ac) in acetic acid (10,11). Studies with a number of PAH indicate that the formation of pyridinium-PAH or acetoxy-PAH by one-electron oxidation with Mn(0Ac)3 or iodine, respectively, is related to the ionization potential (IP) of the PAH. For PAH with relatively high IP, such as phenanthrene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene, no reaction occurs with these two oxidant systems. Another important factor influencing the specific reactivity of PAH radical cations with nucleophiles is localization of the positive charge at one or a few carbon atoms in the radical cation. 

The influence of secondary structure on reactions of deamidation has been confirmed in a number of studies. Thus, deamidation was inversely proportional to the extent of a-helicity in model peptides [120], Similarly, a-hel-ices and /3-turns were found to stabilize asparagine residues against deamidation, whereas the effect of /3-sheets was unclear [114], The tertiary structure of proteins is also a major determinant of chemical stability, in particular against deamidation [121], on the basis of several factors such as the stabilization of elements of secondary structure and restrictions to local flexibility, as also discussed for the reactivity of aspartic acid residues (Sect. 6.3.3). Furthermore, deamidation is markedly decreased in regions of low polarity in the interior of proteins because the formation of cyclic imides (Fig. 6.29, Pathway e) is favored by deprotonation of the nucleophilic backbone N-atom, which is markedly reduced in solvents of low polarity [100][112],... 

Other factors, however, should also be effective. A specific influence of the solvent 101,116) added detergents 12 ) and remote electron donating substituents 119) has been observed. Steric hindrance, which certainly is of influence in the nucleophilic photosubstitution reactions of a-nitronaphthalenes, has been found to alter the reactivity of nitroanisoles... 

With the exception of B = OH-, which relates in fact to an acid-base reaction, the other nucleophiles are potential reductants. After forming the reversible adducts [Eq. (5)], redox reactions are usually operative, leading to the reduction of nitrosyl and oxidation of the nucleophile in Eq. (6). Nevertheless, we will consider first the reaction with B = OH- for the sake of simplicity, and also because it allows for some generalizations to be made on the factors that influence the electrophilic reactivities of different nitrosyl complexes (51). We continue with new results for some N-binding nucleophiles (62,67), which throw light on the mecanisms of N20/N2 production and release from the iron centers. A description of the state of the art studies on the reactions with thiolate reactants as nucleophiles will be presented later. 

Because systematic variations in selectivity with reactivity are commonly quite mild for reactions of carbocations with n-nucleophiles, and practically absent for 71-nucleophiles or hydride donors, many nucleophiles can be characterized by constant N and s values. These are valuable in correlating and predicting reactivities toward benzhydryl cations, a wide structural variety of other electrophiles and, to a good approximation, substrates reacting by an Sn2 mechanism. There are certainly failures in extending these relationships to too wide a variation of carbocation and nucleophile structures, but there is a sufficient framework of regular behavior for the influence of additional factors such as steric effects to be rationally examined as deviations from the norm. Thus comparisons between benzhydryl and trityl cations reveal quite different steric effects for reactions with hydroxylic solvents and alkenes, or even with different halide ions... 

The Michael addition mechanism, whereby sulfur nucleophiles react with organic molecules containing activated unsaturated bonds, is probably a major pathway for organosulfur formation in marine sediments. In reducing sediments, where environmental factors can result in incomplete oxidation of sulfide (e.g. intertidal sediments), bisulfide (HS ) as well as polysulfide ions (S 2 ) are probably the major sulnir nucleophiles. Kinetic studies of reactions of these nucleophiles with simple molecules containing activated unsaturated bonds (acrylic acid, acrylonitrile) indicate that polysulfide ions are more reactive than bisulfide. These results are in agreement with some previous studies (30) as well as frontier molecular orbital considerations. Studies on pH variation indicate that the speciation of reactants influences reaction rates. In seawater medium, which resembles pore water constitution, acrylic acid reacts with HS at a lower rate relative to acrylonitrile because of the reduced electrophilicity of the acrylate ion at seawater pH. 

Steric factors can also play a part in the reactivity of acid derivatives. For example, a bulky group attached to the carbonyl group can hinder the approach nucleophiles and hence lower reactivity. The steric bulk of the nucleophile can also have an influence in slowing down the reaction. For example, acid chloride react faster with primary alcohols than they do with secondary or tertiary alcohols. This allows selective esterification if a molecule has more than one alcohol group present ... 

Steric factors also play an important role in the reactivity of aldehydes and ketones. We may look at the relative ease with which the attacking nucleophile can approach the carbonyl carbon or consider how steric factors influence the stability of the transition state leading to the final product. 

The reactivity of esters in saponification reactions is influenced by steric factors. Branching in both the acyl and alkyl portions of an ester hinders attack of the hydroxide nucleophile. This effect is less dramatic in the alkyl portion of the ester than in the acyl portion because alkyl branching is one atom farther away from the site of attack, but it is still significant. 

Another factor in determining comparative positional reactivity is the localization energy required to produce 50 or some form approaching 50 as the substrate reaches the transition state under the influence of the nucleophile. Experimental results on azines and theoretical considerations warrant the general postulate that the localization energy will be lower when a nitrogen atom is at the... 

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