The Solvent as Nucleophile

Various scales of nucleophilic reactivity for anions have been in use for several years (Swain and Scott, 1953 Edwards, 1956 Pearson et al., 1968 Ritchie, 1972 see also Bunnett, 1963 Ibne-Rasa, 1967 Hartshorn, 1973b), but quantitative scales of solvent nucleophilicity have only recently been developed. Peterson and Waller (1972) derived a scale of solvent nucleophilicity (APW) based on the 

Leaving Group Effects on Relative Snjl Solvolysis Rates 

The four-parameter, linear free energy relationship (9), a more generally applicable equation than eqn (5), had been proposed by 

Winstein et al. (1957). In (9), k, k0 and Y have the same meaning as for eqn (5), m is the sensitivity of the solvolysis of RX to solvent ionizing power, Y, and l is the sensitivity of the solvolysis of RX to solvent nucleophilicity, N. However, this equation was not evaluated until recently, when Bentley et al. (1972) made the following substitutions in the rearranged form (10). Methyl tosylate was 

3- hexafluoropropan-2-ol also have low N values (Table 7). Further comparisons between iVpw and A ts data await a more extensive collection of iVpw values for alcohols. 

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Nucleophilic Solvent Assistance—kinetically significant involvement of the solvent as nucleophile or base by partial bonding (as distinct from general electrostatic solvation) to any atom of the substrate (e.g. a-carbon, j3-hydrogen, etc.) ... 

The difference between these two methods of expressing the magnitude of anchimeric assistance is that the ratios kjk or kjk involve a comparison of two different types of processes an intramolecular displacement, which involves a specific neighboring group as nucleophile (fc ) and an inter-molecular process, which involves the solvent as nucleophile (fcj or one that occurs without nucleophilic assistance (fc ). On the other hand, the effective molarity involves a comparison of two analogous processes that differ only in that one is intramolecular and the other intermolecular. " ... 

This reagent then gives a cyclic selenium ion intermediate which captures the solvent as nucleophile, leading to product. The thiocyanate ion behaves similarly under these reaction conditions. 

If the nucleophilicity of the anion is decreased, then an increase of its stability proceeds the excessive olefine can compete with the anion as a donor for the carbenium ion, and therefore the formation of chain molecules can be induced. The increase of stability named above is made possible by specific interactions with the solvent as well as complex formations with a suitable acceptor 112). Especially suitable acceptors are Lewis acids. These acids have a double function during cationic polymerizations in an environment which is not entirely water-free. They react with the remaining water to build a complex acid, which due to its increased acidity can form the important first monomer cation by protonation of the monomer. The Lewis acids stabilize the strong nucleophilic anion OH by forming the complex anion (MtXn(OH))- so that the chain propagation dominates rather than the chain termination. 

Bonds typically hydrolyzed include carboxylic and phosphoric esters, amides, acetals, amidines, as well as metal ion complexes. (When a nucleophilic substitution reaction uses the solvent as the nucleophile, the reaction is often referred to as solvolysis.)... 

Many SN reactions are carried out using the solvent as the nucleophilic agent. They are called solvolysis reactions and involve solvents such as water, ethanol, ethanoic acid, and methanoic acid. Two examples are... 

The rates for the Sn2 reactions of seven different anionic nucleophiles (Cl-, Br-, I-, OAc-, CN-, SCN- and trifluoromethylacetate-) with methyl / -nitrobenzenesulfonate have been determined in CH2CI2, MeOH, DMSO, and three ionic liquid solvents.122 The reactivity was not correlated with the dielectric constant for the solvents as predicted by the Hughes-Ingold rules and a different nucleophilic order was found in... 

These results provide strong evidence for the role of the solvent as a kinetically significant nucleophile in many secondary solvolyses, and hence suggest that they should be regarded as SN 2 reactions. 

In all the examples given so far, the substrate carries at least one V-o -hydrogen atom. The anodic oxidation of fully substituted amides, like N, V-di-/cr/-butylformamide and V-formyl-2,2,6,6-tetramethylpiperidine, in MeOH would be expected to follow a different pathway. The products isolated after 12-14 F, methyl V-/cr/-butylcarbamate and V-methoxycarbonyl-2,2,6,6-tetramethylpiperidine, respectively [Eq. (37)] [102], indicated that the primarily formed substrate radical cation looses the formyl proton. Further oxidation of the neutral radical leads to the cation, which may either undergo cleavage, as in Eq. (38), or nucleophilic attack by the solvent, as in Eq. (39). 

Nucleophilic substitution reactions of dansyl chloride with anilines (entry 16)128 are reported in various protic solvents. Interestingly, the Px values are in parallel with the rates, which are dependent on the dielectric constant (e)49 of the solvent as can be seen from the data presented for each solvent in the order [e k2 (xlO4 M 1 s 1 at 30 °C for X = H) px], MeOH [32.66 107 0.67], EtOH [24.55 37.7 0.55], w-PrOH [20.45 8.71 0.50], 2-PrOH [19.92 5.33 0.41], n-BuOH [17.51 3.07 0.34], MeCN [35.94 13.7 0.72]. In the aprotic solvent MeCN, the rate is somewhat slow despite the largest s and Px values. Since the reactivity changes in parallel to the selectivity, the RSP is violated, and a stepwise mechanism through an intermediate can be excluded. Solvatochromic analysis also suggested that the reaction proceeds via an associative S 2 mechanism. 

Nucleophilic substitution reactions may involve several different combinations of charged and uncharged species as reactants. The equations in Scheme 4.1 illustrate the four most common charge types. The most common reactants are neutral halides or sulfonates, as illustrated in Parts A and B of the scheme. These compounds can react with either neutral or anionic nucleophiles. When the nucleophile is the solvent, as in Entries 2 and 3, the reaction is called a solvolysis. Reactions with anionic nucleophiles, as in Entries 4 to 6, are used to introduce a variety of substituents such as cyanide and azide. Entries 7 and 10 show reactions that involve sulfonium ions, in which a neutral sulfide is the leaving group. Entry 8 involves generation of the diphenylmethyl diazonium ion by protonation of diphenyldiazomethane. In this reaction, the leaving... 

A series of quantitative data for solvent effect on the aminolysis of nitrophenyl esters attached to polyacrylamides have also been reported [41b]. These data are in broad agreement with the above-mentioned observations. However, the apparent solvent effects in chemical transformation of polymers must be interpreted in terms of a dual function, i.e. polymer solvation and solvent catalysis . For example, DMSO is a poor solvent for copol3 AOTq)-styrene), but a good solvent for polymers carrying amide residues. It should also be noted that alcohols and water are not usually suitable as solvent for chemical transformation of activated esters, because they may them lves enter the reaction as nucleophiles. 

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