Effects of Solvent on Nucleophilicity

The effect of solvent on nucleophilicity has already been discussed (p. 438-445). 

The effect of solvent on nucleophilic tendencies relative to SCN is shown by solvent activity coefficients. Equation (40) is derived from equation (9) and applies to reactions of methyl iodide with a series of... 

Effect of Solvent on Nucleophilic Strengths of Anionic Ligands (expressed as l(PA/mol 1 s ) for Reaction rran5-[PtCl2(pip)2] + F -> traiM-[PtClY(pip)2] + Cl ... 

Effect of Solvent on Elimination versus Substitution. Increasing polarity of solvent favors Sn2 reactions at the expense of E2. In the classical example, alcoholic KOH is used to effect elimination, while the more polar aqueous KOH is used for substitution. Charge-dispersal discussions, similar to those on page 450, only partially explain this. In most solvents, SnI reactions are favored over El. The El reactions compete best in polar solvents that are poor nucleophiles, especially dipolar aprotic solvents" A study made in the gas phase, where there is no solvent, has shown that when 1-bromopropane reacts with MeO only elimination takes place no substitution even with this primary substrate." ... 

The principal tumor-localizing component of Hematoporphyrin Derivative (HPD) has been demonstrated to be dimeric and trimeric hematoporphyrins (HP) interconnected with ester groups. Synthetic analogs as well as model compounds are used in our study to conclude that the reaction conditions employed in the traditional HPD preparation promote a nucleophilic substitution of the acetate group of one HP-acetate molecule by an propionate anion of another HP molecule. The effect of solvent on the stability and structural conformation of the diporphyrin esters have also been examined by spectroscopic methods. 

To conclude this section on the effect of solvent on a-nucleophilicity, we refer to the current, rather controversial, situation pertaining to gas-phase smdies and the a-effect. As reported in our review on the a-effect and its modulation by solvent the gas-phase reaction of methyl formate with HOO and HO , which proceeds via three competitive pathways proton abstraction, nucleophilic addition to the carbonyl group and Sat2 displacement on the methyl group, showed no enhanced nucleophilic reactivity for HOO relative to This was consistent with gas-phase calculational work... 

Methyl trisnorshionanoate (126) has been synthesized from friedelan-19a-ol (127) via the ring-contracted intermediate (128) and the trisnor-ketone (129). Irradiation of (129) in methanol afforded the desired ester (126). An investigation of the effect of solvent on the backbone rearrangement of 3/8,4/3-epoxyshionane (130) by boron trifluoride etherate has shown that nucleophilic solvents tend to interrupt the rearrangement at an early stage (see Vol. 6, p. 130). 

The development of these various solvent parameters and scales has been accompanied by the realization that there are uncertainties in the physical property of the solvent that is correlated by a particular parameter in cases where systematic changes in solvent structure affect several solvent properties. Consider a reaction that shows no rate dependence on the basicity of hydroxylic solvents, and a second reaction that proceeds through a transition state in which there is a small transition state stabilization from a nucleophilic interaction with the hydroxyl group. The rate constants for the latter reaction will increase more sharply with changing solvent nucleophilicity than those for the former, and they should show a correlation with some solvent nucleophilicity parameter. This trend was observed in a comparison of the effects of solvent on the rate constants for solvolysis of 1-adamantyl and ferf-butyl halides, and is consistent with a greater stabilization of the transition state for reaction of the latter by interaction with nucleophilic solvents. ... 

Similar information is available for other bases. Lithium phenoxide (LiOPh) is a tetramer in THF. Lithium 3,5-dimethylphenoxide is a tetramer in ether, but addition of HMPA leads to dissociation to a monomer. Enolate anions are nucleophiles in reactions with alkyl halides (reaction 10-68), with aldehydes and ketones (reactions 16-34, 16-36) and with acid derivatives (reaction 16-85). Enolate anions are also bases, reacting with water, alcohols and other protic solvents, and even the carbonyl precursor to the enolate anion. Enolate anions exist as aggregates, and the effect of solvent on aggregation and reactivity of lithium enolate anions has been studied. The influence of alkyl substitution on the energetics of enolate anions has been studied. ... 

Effect of solvent on rate Rate increases with increasing polarity of solvent as measured by its dielectric constant e. (Section 8.12) Polar aprotic solvents give fastest rates of substitution solvation of Nu is minimal and nucleophilicity is greatest. (Section 8.12)... 

Effects of Solvation on Nucleophilic Reactivity in Hydroxylic Solvents... 

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