Electrophilic solvent assistance

Kinetic solvent isotope effect as a measure of electrophilic solvent assistance to bromide ion departure limiting value Br- = 1.35 in MeOL. From h>r and kinetic data in water, methanol, ethanol and their aqueous mixtures. c( aqEtoH/ AcOH>r measurement of nucleophilic solvent assistance. Calculated from data in Ruasse and Dubois (1975) and Ruasse et al. (1978). Ruasse and Lefebvre (1984). - Ruasse and Lefebvre (unpublished results). "Ruasse (1985). 

SnI reactions of secondary and tertiary substrates R3C—X e.g. 2-adamantyl tosylate [665], t-butyl heptafluorobutyrate [666]) proceed via activated complexes with high carbenium ion character to give ion-pair intermediates. They exhibit electrophilic solvent assistance in protic solvents SOH (H-bonding to the leaving group), but they are practically insensitive to changes in solvent nucleophihcity cf. Eq. (5-135). 

A comparison of Eqs. (7-52) and (7-55a) shows that both treatments give similar results, with opposite signs of the solvent Lewis-addity and basicity parameters. This is in agreement with the given reaction mechanism, involving simultaneous nucleophilic and electrophilic solvent assistance. 

Solvolytic displacement reactions can be affected by solvents in several ways, including nucleophilic solvent assistance (NSA) and electrophilic solvent assistance (ESA). NSA can be defined as electron donation from solvent to the developing positive dipole of a reacting C-X bond, and ESA can be defined as electron acceptance by the solvent from the leaving group, I. 

The most significant difference between brominations in protic and non-protic solvents concerns the kinetic law. Whereas in protic media the reaction is first-order in bromine, in halogenated media it is second-order (Bellucci et ai, 1980). CTC ionization is electrophilically assisted by hydrogen bonding by a protic solvent to the leaving bromide and leads to a bromonium-bromide ion pair. In non-protic media, assistance to the bromination step is provided by a second bromine molecule, leading to a bromonium-tribromide ion pair. In other words, in protic media bromination is solvent-assisted (56) while in halogenated media it is bromine-catalysed (57). 

The search for electrophilic catalysis could in principle be aided by use of tertiary amines as nucleophiles, in which case an intramolecular or solvent assisted proton shift, formulated in [13] and [14], is eliminated. Thus Ayediran, Bamkole and Hirst (1974) studied salt effects on the reactions of 4-fluoro- and 4-chloronitro-benzene with trimethylamine in DMSO, which proceed according to equations (29) and (30). It had been noted (Suhr, 1967) that the... 

An Sn2 (intermediate) mechanism has been proposed as a result of the consideration of the dependence of Sn1/Sn2 solvolysis rates on electrophilic (EPA) and nucleophilic (EPD) solvent assistance [664, 665]. 

HVZ MPV SE1 SE1(N) Hell-V olhard-Zelinskii. Meerwein-Ponndorf-Verley reduction. Electrophilic substitution unimolecular. SEI pathway in which a nucleophile (which may be the solvent) assists in the removal of the electrofuge. 

Kevill and co-workers first address the much-debated issue of nucleophilic involvement in solvolysis of tert-butyl derivatives. Interestingly, the tert-butyl sulfonium salt shows more rate variation with solvent changes than does the 1-adamantyl salt. In particular, the tert-butyl salt shows a rate increase in aqueous TFEs (where both Y and N increase) that is not found for 1-adamantyl. Because a variation in Y cannot explain the result, Kevill argues that the tert-butyl derivative is receiving nucleophilic solvent assistance. On the basis of the available evidence, Harris et al. (Chapter 17) propose that tert-butyl chloride is inaccurately indicated by some probes to receive nucleophilic solvent assistance because the model system (1-adamantyl chloride) has a different susceptibility to solvent electrophilicity. Kevill and coworkers disagree with this proposal, noting that essentially the same tert-butyl to 1-adamantyl rate ratio is found for the chlorides and the sulfonium salts if solvent electrophilicity were important in one case but not the other, then the rate ratio should vary. 

The development of quantitative scales of solvent nucleophilicity based on solvolysis reactions is reviewed. Effects of solvent nucleophilicity are illustrated by product studies, by correlations of kinetic data, and by quantitative estimates of competing nucleophilic pathways, including competing solvent-assisted and anchimerically assisted pathways. The problem of separating quantitatively the nucleophilic and electrophilic solvent contributions to reactivity is discussed. Recent results on the nucleophilicities of aqueous sulfuric acid mixtures are presented. 

Separation of Nucleophilic and Electrophilic Contributions to Solvation Effects. The discussion on the appropriate choice of m value for the N0Ts scale (equation 7) is part of a more general problem of dissecting the nucleophilic contributions (corresponding to the IN term in equation 5) and electrophilic contributions (included in the mY term in equation 5) to solvent effects. When a substrate reacts by a nucleophilically solvent assisted pathway, m decreases and l increases, often in a uniform manner (equation 12). Schadt et al. proposed (3) that an increase in nucleophilic assistance (increase in l) caused delocalization of positive charge, which led to a decrease in m. All of the deviations from the rates expected for SN1 (kc) reactivity were attributed to nucleophilic solvent assistance (3) Schadt et al. (3) assumed that m values for kc processes would be the same as for 2-adamantyl (II), and more recent data for 1-adamantyl (I), 1-adamantylmethylcarbinyl, and 1-bicyclo[2.2.2]octyl tosylates support this assumption (4, 53). 

Comparison of the calculated nucleophilic accelerations of 9, 17, and 106 to the degree of inversion (72, 74, and 87%, respectively) for Vla-c shows that even though the kinetic effects of solvent assistance are significant, this fact does not lead to the complete inversion characteristic of the SN2 reaction as found in acetolysis of 2-octyl tosylate (45). The best description of the first intermediate in the solvolysis of Vla-c would thus appear to be the solvated ion pair shown in Scheme II. In this species, the solvent is involved in nucleophilic solvation of the central carbon as well as the remainder of the carbocation and also participates in electrophilic solvation of the anion. Numerous solvent molecules are involved, and no strong interaction of a single nucleophilic solvent molecule at the central carbon leading to exclusive inversion occurs. 

In addition to polarity and nucleophilicity toward the bromonium ion, other solvent properties may come into play. The rate-limiting step in electrophilic bromine addition is thought to be the conversion of a CT complex to a cation-bromide ion pair, which is consistent with the observation that the rate constant for bromine addition increases as solvent polarity increases. Solvent may also electrophilically assist the removal of the bromide ion from the alkene-Br2 CT complex by hydrogen bonding to a developing bromide ion (Figure 9.6). It has been estimated that this electrophilic solvent participation can lower the energy of bromonium ion formation by 60 kcal/mol. ° Additional support for the role of electrophilic... 

Molecular chlorine is believed to be the active electrophile in uncatalyzed chlorination of aromatic compounds. Simple second-order kinetics are observed in acetic acid. The reaction is much slower in nonpolar solvents such as dichloromethane and carbon tetrachloride. Chlorination in nonpolar solvents is catalyzed by added acid. The catalysis by acids is probably the result of assistance by proton transfer during the cleavage of the Cl-Cl bond. ... 

It is claimed that a measures electrophilic assistance by the solvent, b measures nucleophilic assistance, and that at least three, and sometimes four, parameters are required to perform a dissection into these separate effects. These workers also decomposed Y into ir and a contributions, and N into tt and p contributions. Abraham et al. have compared the performance of Eqs. (8-79) and (8-80) and find that they are about equally successful in correlating data. 

It is clear from the results that there is no kinetic isotope effect when deuterium is substituted for hydrogen in various positions in hydrazobenzene and 1,1 -hydrazonaphthalene. This means that the final removal of hydrogen ions from the aromatic rings (which is assisted either by the solvent or anionic base) in a positively charged intermediate or in a concerted process, is not rate-determining (cf. most electrophilic aromatic substitution reactions47). The product distribution... 

It has been shown (ref. 21) that a solvent which is both protic and nucleophilic, assists the formation of the bromination intermediates of moderately reactive olefins as styrenes in two ways, (Scheme 7). Firstly, the solvent initiates bromide ion formation electrophilically and, secondly, favours... 

In these solvents at sufficiently low Br2 concentration (< 10-3 m) the kinetics are first order both in the olefin and in Br2 and the main solvent effect consists of an electrophilic solvation of the departing Br ion. A nucleophilic assistance by hydroxylic solvents has also been recognized recently (ref. 26) (Scheme 10). So far, return during the olefin bromination in methanol had been admitted only for alkylideneadamantanes, and was ascribed to steric inhibition to nucleophilic attack at carbons of the bromonium ion (ref. 26). 

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