Solvents electrophilicity

In the laboratory, alkenes are often hydrated by the oxymercuration procedure. When an alkene is treated with mercury(II) acetate Hg(02CCH3)2, usually abbreviated Hg(OAc)2l in aqueous tetrahydrofuran (THF) solvent, electrophilic addition of Hg2+ to the double bond rapidly occurs. The intermediate orgnnomercury compound is then treated with sodium borohydride, NaBH4, and an alcohol is produced. For example ... 

Substituted 3,6-dialkoxy-2,5-dihydropyrazines are regioselectively metalated by strong alkyl-lithium bases, such as butyllithium, (l-methylpropyl)lithium, fcrf-butyllithium, or lithium diiso-propylamide, at the less substituted carbon atom (C5). Metalation proceeds at low temperatures (in general, below — 70 C) in THF as solvent. Electrophiles suitable for alkylation of the lithiated derivatives include alkyl iodides, bromides and chlorides, as well as alkyl methanesulfonates, 4-methylbenzenesulfonates and trifluoromethanesulfonates. The electrophile adds trans to the substituent at C2 in a highly stereoselective fashion, with typical diastereomeric excesses of greater than 90% (syn addition has been reported in only one case where a-methylphenyl alanine was used as chiral auxiliary and an alkyl trifluoromethanesulfonate as electrophile18). 

With alkanenitriles179 or benzonitrile196,197 as solvents, electrophilic arylations of the nitrogen atom occur and, V-arylamides are formed (Ritter reaction) together with the expected fluorinated compounds. 

Generally, the rate of alkaline hydrolysis of a series of substituted phenyl benzoates was decreased in the presence of 0.5 m BiuNBr, the retardation being larger for esters with electron-donating substituents. The data from 22 esters were fitted to a multiparameter equation, the results showing that solvent electrophilicity was the main factor responsible for changes in the ortho, para and meta polar substituent effects with medium.15... 

Rates of the alkaline hydrolysis of 12 ortho-, meta- and ) ara-X-substituted phenyl tosylates, 4-MeC6H4S02C6H4X, in aqueous 0.5 m Bu4NBr over a wide temperature range have been analysed using the modified Fujita-Nishioka multi-parameter equation. It was concluded from both these and previously reported data by the same group that solvent electrophilicity was the main factor responsible for changes in the ortho, meta and para polar substituent effects with medium.60... 

Reference NuH Activation/Solvent Electrophile Catalyst Products Target... 

Triethylphosphine oxide contains a highly basic oxygen atom, which is easily accessible to solvent electrophilic attack. This causes a polarization of the P=0 bond and a downfield shift of the 31P NMR signal. The observed chemical shifts (5) referred to the reference solvent n-hexane and extrapolated to infinite dilution may be taken as a measure of the acceptor properties of the solvents. Hence, the acceptor number (AN) is defined as follows ... 

The value of kd was obtained from the determination of triplet lifetimes by measuring the decay of phosphorescence and found to be insensitive to changes in solvent polarity. The k2 values derived from Eqs. 10 and 11 were correlated with solvent parameters using the linear solvation energy relationship described by Abraham, Kamlet and Taft and co-workers [18] (Eq. 12), which relates rate constants (k) to four different solvation parameters (1) or the square of the Hildebrand solubility parameter (solvent cohesive energy density), (2) n or solvent dipolarity or polarizability, (3) a, or solvent hydrogen bond donor acidity (solvent electrophilic assistance), and (4) or solvent hydrogen bond acceptor basicity (solvent nucleophilic assistance). 

The procedure for parameterization of solvent electrophilicity has been criticized, mainly because it was found that the use of t(30) instead of E in the multiple regression treatment of solvent effects is often quite successful see reference [15, 116] for examples. It has been shown that values of t(30) and E are linearly correlated, at least for solvents with an t(30) value of greater than ca. 40 kcal/mol [178]. This calls into question the value of Koppel and Palm s division of t(30) into pure electrophilicity effects and non-specific effects by means of Eq. (7-51). 

Direct C-H activation of hydrocarbon by means of transition metals has also been explored. Cyclohexane reacted with Pd(OAc)2 in the presence of potassium persulfate-trifluoroacetic acid under CO pressure and produced the desired cyclo-hexanecarboxylic acid in low yields and TON (eq. (13)). The electrophilic carbox-ylation is explained by the change of Pd(OAc)2 to Pd(OCOCp3)2 in trifluoroacetic acid as solvent. Electrophilic attack on a C-H bond should give an alkyl Pd complex. CO insertion followed by reductive elimination affords a reactive mixed anhydride which was detected before workup. 

Substrate Solvent Electrophile Product Yield GLC. (isolated)... 

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. 

In Chapter 20, F rca iu derives a novel measure of solvent nu-cleophilicities. First, protonation equilibria of benzene derivatives are used to measure acidity of a set of acids. Then, by measurement of the effect of weakly basic solvents (such as trifluoroacetic acid) on these equilibria, basicities of the solvents are calculated. Interestingly, these solvent basicities compare quite well with the solvent nucleophilicities calculated by Peterson (discussed previously). F rca iu also considers the anion-solvating ability of hydrogen-bonding solvents and concludes, in agreement with Chapter 17 and in disagreement with Chapters 18 and 19, that solvent electrophilicity must be considered as a separate variable. 

Points for TFE and HFIP, as well as hydroxylic and nonhydroxylic solvents, fit the correlation nicely. Also, a weak, but statistically significant, dependency on solvent nucleophilicity 0 exists. Also noteworthy is the large dependence of the reaction rate on solvent electrophilicity. These results indicate that application of the SCE to reaction rates is legitimate. 

We are currently applying further kinetic tests to the SCE to determine the range of its applicability to kinetic phenomena. One such test, for example, is to determine the sensitivity of reaction rate of sulfonium salt solvolysis to solvent electrophilicity (i.e. its a value). Because the leaving group is neutral in this case, such a reaction would be expected to have a very weak dependence on electrophilicity. 

Recently, Swain et al. (7) have put forward equation 2, where Alog k is the incremented log k relative to the lowest value in the series, A and B are measures of solvent electrophilicity and nucleophilicity, and a, b, and c are determined by details of the solvolysis under consideration. Although this equation appears to have an advantage over equation 1 in that A and B values can be obtained without the study of solvolysis reactions, use of such values frequently leads to unreasonable predictions (8). 

Other sets of N values were determined more directly from the rates of reaction between nucleophiles and tetramethylchloronium ions (20a) and the counterion was derived from antimony pentafluoride (20b) in sulfur dioxide solutions (20a) and of reaction between triethyloxonium fluorophosphate and nucleophiles used as solvents (21). The first approach (20a) has been criticized (21) on the ground that nucleophilicity of individual molecules or small clusters might be different from that of the compound as a solvent. The second approach (21) might be questioned for the assumption that solvent electrophilicity (18) has no effect on the measured rates. 

Several other treatments of solvent effects on solvolysis rates have been developed. The equations typically include several terms related to (a) macroscopic nonspecific solvent properties, such as the dipole moment and dielectric constant (b) empirical polarity criteria, such as Ej.(30) (c) solvent electrophilicity and nucle-ophilicity parameters and (d) terms related to solvent cohesivily. The last term accounts for the difference in work required to disrupt structure within the solvent, when, for example, there is expansion in volume between reactants and the TS. 

Schlosser [80] andVoyer [81] reported that N-Boc-N-methylbenzylamine 106 can be deprotonated with 5ec-BuLi in the presence of (-)-sparteine. The resulting organolithium can be trapped with electrophiles to provide a-substituted benzylamines 107 with high enantioselectivities (Scheme 31). Schlosser and coworkers showed that the reaction pathway of N-methyl-hl-Boc benzylamines 107 is an asymmetric deprotonation followed by racemization and asymmetric substitution, and provided rationalization of solvent effects in terms of ion paired species [80]. The enantioselectivity of this reaction sequence is highly dependent on the solvent, electrophile, and reaction time. 

In modifying sucrose for the preparation of sucrose esters, great attention must be focused on the structure, the conformation of sucrose in solution, the reaction conditions (solvent, electrophilic reagent, catalysis, temperature, etc.) and the purification procedures of the reaction product. 

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