Nucleophilicity solvents

Over a decade of research, we were able to show that practically all conceivable carbocations could be prepared under what became known as stable ion conditions using various very strong acid systems (see discussion of superacids) and low nucleophilicity solvents (SO2, SO2CIF, SO2F2, etc.). A variety of precursors could be used under appropriate conditions, as shown, for example, in the preparation of the methylcyclopentyl cation. 

In superacidic media, the carbocationic iatermediates, which were long postulated to exist duting Friedel-Crafts type reactions (9—11) can be observed, and even isolated as salts. The stmctures of these carbocations have been studied ia high acidity—low nucleophilicity solvent systems usiag spectroscopic methods such as nmr, ir, Raman, esr, and x-ray crystallography. 

The photolysis of the diazopyrazolone (369 X = N2, R = Me) in methanol yields two isomeric forms of methyl 3-phenylazo-2-butenoate (394) (80CC1263). The azo esters may arise via protonation of the carbene (395) with a concurrent opening of the ring by the nucleophilic solvent. 

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

Reactant structure will also influence the degree of nucleophilic solvent participation. Solvation is minimized by steric hindrance. The 2-adamantyl system is regarded as being a... 

Table S.16 presents data on some representative nucleophilic substitution processes. The first entry illustrates the use of 1-butyl-l-r/p-bromobenzenesulfonate to dononstrate at primary systems react with inversion, even under solvolysis conditkms in formic acid. The observation of inversion indicates a concerted mechanism in fids weakly nucleophilic solvent.

Evidently, since there is no appreciable rate acceleration, this participatimi is not very strong at the transition state. Nevertheless, the participation is strong enough to control stereochemistry. When mote nucleophilic solvents are used (e.g., acetic acid), participation is not observed, and the product is 100% of inverted configuration. 

When 2-butyl tosylate is solvolyzed in the less nucleophilic solvent triiluoroacetic acid, a different result emerges. The extent of migration approaches the 50% that would result from equilibration of the two possible secondary cations. 

There is usually a competing reaction with solvent when lydrogen halide additions to alkenes are carried out in nucleophilic solvents ... 

These reactions do not appear to involve free carbocations, because they proceed effectively in nucleophilic solvents that would successfully compete with halide or similar anions for free carbocations. Also, rearrangements are unusual under these conditions, although they have been observed in special cases. 

In the case of cycloheptenone and larger rings, the main initial photoproducts are the -cycloalkenones produced by photoisomerization. In the case of the seven- and eight-membered rings, the double bonds are sufficiently strained that rapid reactions follow. In nonnucleophilic solvents dimerization occurs, whereas in nucleophilic solvents addition occurs. ... 

Mercury(II) trifluoroacetate is a good electrophile that is highly reactive toward carbon-carbon double bonds [52, 53, 54] When reacting with olefins in nucleophilic solvents, it usually gives exclusively mercurated solvoadducts, but never products of skeletal rearrangement Solvomercuration-demercuratton of alkenes with mercury(II) trifluoroacetate is a remarkably effective procedure for the preparation of esters and alcohols with Markovnikov s regiochemistry [52, 5J] (equation 24)... 

Line No. Pyridine substituents Nucleophile (solvent) Rate constant" (temp. °C) 10 fc liter mole- seo-i Activation energy kcal mole-1 Entropy of activation cal mole i deg-i Frequency factor logioA Ref. 

Line No. Benzene substituents Nucleophile Solvent Rate constant (temp. °C) 106 jc liter mole-1 see-i Energy of activation keal mole-1 Frequency factor logioA Ref. 

No. substituents Nucleophile (solvent) liter mole-1 sec-i kcal mole-1 calmole-ideg" -1 Ref. W 9... 

The solvent used plays an important role, since it can stabilize the organomag-nesium species through complexation. Nucleophilic solvents such as ethers—e.g. diethyl ether or tetrahydrofuran—are especially useful. The magnesium center gets coordinated by two ether molecules as ligands. 

In a nucleophilic solvent, the organomagnesium species not only exists as RMgX, but is rather described by the Schlenk equilibrium ... 

Strong evidence has been provided that the photoxygenation proceeds via a hydroperoxide intermediate which is transformed into an epoxide. The epoxide is then opened by the nucleophilic solvent. 

The electrochemical oxidation of cyclic and acyclic, V-monosubstitilted and ATY-disubstituted amides and carbamates in a nucleophilic solvent, known as the Ross-Eberson-Ny berg reaction, is a synthetically very useful, clean and efficient method for the introduction of a-oxygen substituents under mild reaction conditions6 1 0. 

Dediazoniation in Highly Nucleophilic Solvents and in the Presence of Good Nucleophiles... 

The 15N content was indeed lower when the experiment was performed This result justified the publication of a preliminary communication (Bergstrom et al., 1974). Later work (Hashida et al., 1978 Szele and Zollinger, 1978a Maurer et al., 1979) involving sophisticated statistical treatments suggested that, in a weakly nucleophilic solvent such as trifluoroethanol, the phenyl cation is formed in two steps and not in one, as in mechanism B (see Scheme 8-4 in Sec. 8.3), the first intermediate being a tight ion-molecule pair. 

The most reasonable mechanism for this transformation, in accord with that suggested by van Tamelen et al. for the dilute acid photolysis, is initial photoisomerization to 2 followed in this case by thermal conversion of the Dewar tropylium ion to 7. The isomerization of 2 to 7 has been reported to be very rapid at temperatures below —60°, and it has been shown, in addition that, in nucleophilic solvents, capture of 2 competes very efficiently with isomerization (Lustgarten et al., 1967). 

Perhaps the most important single function of the solution environment is to control the mode of decomposition of reaction intermediates and hence the final products. This is particiflarly true in the case of electrode reactions producing carbonium ion intermediates since the major products normally arise from their reaction with the solvent. It is, however, possible to modify the product by carrying out the electrolysis in the presence of a species which is a stronger nucleophile than the solvent and, in certain non-nucleophilic solvents, products may be formed by loss of a proton or attack by the intermediate on further starting material if it is unsaturated. The major reactions of carbonium ions are summarized in Fig. 6. 

An important problem encountered with polymer electrodes is that of overoxidation. It occurs after reversible charging of the electrode at high oxidation potentials and leads to polymer degeneration. The results of thorough studies show that such degenerative mechanisms are promoted by the nucleophilicity of the solvent. Especially the activity of water leads to the formation of quinone-type compounds, to the cleavage of C—C bonds, the liberation of CO2, and the formation of carboxylic acids Hence, there is a clear tendency to avoid both nucleophile solvents... 

This stereospecific reaction is, therefore, a rare example of stereochemical control by nucleophilic solvent assistance of an ionization process. 

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