Limiting solvolysis

Let us now consider Scheppele s discussion of the solvolysis of 2-d-exo- and -endo-bicyclo[2.2.1]hept-2-yl p-nitrobenzoates and p-toluenesulfonates. A maximum a isotope effect of 1 22 is suggested for the limiting solvolysis of simple secondary... 

In contrast to typical mono- or acyclic substrates (e. g.,isopropyl), 2-adaman-tyl derivatives are also found to be insensitive to changes in solvent nucleophilicity. A variety of criteria, summarized in Table 13, establish this point. In all cases, the behavior of 2-adamantyl tosylate is comparable to that observed for its tertiary isomer but quite unlike that observed for the isopropyl derivative. Significant nucleophilic solvent participation is indicated in the solvolysis reactions of the isopropyl system. The 2-adamantyl system, on the other hand, appears to be a unique case of limiting solvolysis in a secondary substrate 296). The 2-adamantyl/ isopropyl ratios in various solvents therefore provide a measure of the minimum rate enhancement due to nucleophilic solvent assistance in the isopropyl system 297). 

Let us now consider Scheppele s discussion of the solvolysis of 2-d-exo- and -endo-bicyclo[2.2.1] hept-2-yl p-nitrobenzoates and p-toluenesulfonates. A maximum a isotope effect of 1 22 is suggested for kH/kD for the limiting solvolysis of simple secondary sulphonates (solvolyses where the rate is not affected by the nucleophilicity of the medium). The endo-esters yield a similar value which might be taken to imply the absence of steric hindrance in their reaction. However, whereas the maximum isotope effect for the simple sulphonates is believed to arise partly from an activated complex in the conversion of the internal ion pair into a solvent-separated ion pair, B - C, the effect in the endo-norbomyl compounds is suggested to arise during the transition state involved in the formation of the intimate ion pair, A - B. The latter is deduced from the fact that polarimetric and titrimetric rate constants are the same in acetic acid, aqueous acetone and ethanol (Winstein and Trifan, 1949 and 1952). If this is the case, the endo-effect of 1-20 should be... 

The relationship between the reaction in nonaqueous solvents and that in water is obscure. Since the kinetics are different, it is likely that the mechanism is also different. In methanol the chloride-catalyzed reaction is second order with respect to iron (II) whereas ligand-catalyzed reactions show only first-order dependence on ferrous ion in aqueous solution. In water, rate-limiting solvolysis of species such as XFe 02, to produce H02, may occur simply because formation of the binuclear compound, required for the rate-limiting step in methanol, is inhibited by strong solvation of iron (II) in aqueous solution. 

Pure WCl6 alcohol solution shows slow, limited solvolysis at room temperature, accompanied by generation of HCl up to a low concentration, which ends up with coloration in blue (methanol) or red (ethanol). It is also reported that sodium iodide in acetone exchanges all chloride ligands of tungsten. With sodium ethoxide in ethanol, a soluble... 

As previously pointed out, the rates of solvolysis in various media can be best summarized in terms of the ionizing power and nucleophilicity of the solvent, as suggested by Winstein et In a limiting solvolysis, the rate... 

The points that we have emphasized in this brief overview of the S l and 8 2 mechanisms are kinetics and stereochemistry. These features of a reaction provide important evidence for ascertaining whether a particular nucleophilic substitution follows an ionization or a direct displacement pathway. There are limitations to the generalization that reactions exhibiting first-order kinetics react by the Sj l mechanism and those exhibiting second-order kinetics react by the 8 2 mechanism. Many nucleophilic substitutions are carried out under conditions in which the nucleophile is present in large excess. When this is the case, the concentration of the nucleophile is essentially constant during die reaction and the observed kinetics become pseudo-first-order. This is true, for example, when the solvent is the nucleophile (solvolysis). In this case, the kinetics of the reaction provide no evidence as to whether the 8 1 or 8 2 mechanism operates. 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

The real world of Sn reactions is not quite as simple as the discussion has so far suggested. The preceding treatment in terms of two clearly distinct mechanisms, SnI and Sn2, implies that all substitution reactions will follow one or the other of these mechanisms. This is an oversimplification. The strength of the dual mechanism hypothesis and its limitations are revealed by these relative rates of solvolysis of alkyl bromides in 80% ethanol methyl bromide, 2.51 ethyl bromide, 1.00 isopropyl bromide, 1.70 /er/-butyl bromide, 8600. Addition of lyate ions increases the rate for the methyl, ethyl, and isopropyl bromides, whereas the tert-butyl bromide solvolysis rate is unchanged. The reaction with lyate ions is overall second-order for methyl and ethyl, first-order for tert-butyl, and first- or second-order for the isopropyl member, depending upon the concentrations. Similar results are found in other solvents. These data show that the methyl and ethyl bromides solvolyze by the Sn2 mechanism, and tert-butyl bromide by the SnI mech-... 

Where Br nucleophilically promotes the Br+/OTf- elimination to generate free Br2 and cyclohexene. This process requires that the rate of solvolysis of 4 be linearly dependent on [Br ]. However, control (ref. 15) kinetics experiments indicate that the rate constant for solvolysis of 4 in HOAc or MeOH are independent of Br" thus generation of free Br2 must occur after the rate limiting step. This nicely confirms the previous conclusion based upon the invariance of the n0a+10hV9h ratio on [Br]. 

Bronlc acids containing electron-capturing subsitituents were developed by Poole and co-workers. Table 8.19 (451,535,536). In terms of volatility, stability of derivatives, and response to the electron-capture detector the 3,5-bis(trifluoromethyl)benzeneboronic acid, 2,4-dichlorobenzeneboronic acid, and 4-bromo-benzeneboronic acid were recommended for general applications. In particular, the 3,5-bis(trifluoromethyl)benzeneboronate derivatives are remarkably volatile, more so than the benzeneboronates, and are suitable for the analysis of bifunctional compounds of low volatility. All the benzeneboronate derivatives are susceptible to solvolysis which is the primary limitation to their general use for trace analysis. 

By complexation of MnNaY with 1,4,7-trimethyltriazacyclononane, a new heterogeneous catalyst was obtained for olefin epoxidation with H202. Excellent epoxide selectivities were obtained, with limited epoxide solvolysis. The oxygenation appears to go through a radical intermediate. The manganese trizacyclononane epoxidation catalyst was also heterogenized via surface gly-cidylation.103... 

All are tertiary halides so that attack by the S mode would not be expected to occur on (16) or (17) any more than it did on (8) (cf. p. 82). Sn2 attack from the back on the carbon atom carrying Br would in any case be prevented in (16) and (17) both sterically by their cagelike structure, and also by the impossibility of forcing their fairly rigid framework through transition states with the required planar distribution of bonds to the bridgehead carbon atom (cf. p. 84). Solvolysis via rate-limiting formation of the ion pair (SN1), as happens with (8) is... 

Solvolysis of the p-MeO and p-Me chlorides is found to be faster (p-MeO 800 times) than would have been predicted from their op. values. This stems from the stabilisation, by through-conjugation, of the carbocationic intermediates (21a and 21b) which are developing during the slow, rate-limiting step of the overall reaction ... 

The major defect of the Grunwald-Winstein treatment is that it is limited in its scope. It has been applied to reactions other than halide solvolysis, but is in general restricted to those reactions for which the major contribution to the rate-limiting step is of the form ... 

Electronic effects upon rates of solvolysis of benzoyl chlorides suggest that the mechanism, i.e. the extents of rehybridization of chloride and carbonyl oxygen atoms, depends upon the solvent. In aqueous acetone of low water content, a plot of log k against a is linear and p 2 for a limited range of substituents, whereas in moist formic acid the corresponding plot also is... 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

This reaction proceeds via the transition state illustrated in Fig. 10.2. An Sn2 reaction (second order nucleophilic substitution) in the rate limiting step involves the attack of the nucleophilic reagent on the rear of the (usually carbon) atom to which the leaving group is attached. The rate is thus proportional to both the concentration of nucleophile and substrate and is therefore second order. On the other hand, in an SnI reaction the rate limiting step ordinarily involves the first order formation of an active intermediate (a carbonium ion or partial carbonium ion, for example,) followed by a much more rapid conversion to product. A sampling of a and 3 2° deuterium isotope effects on some SnI and Sn2 solvolysis reactions (i.e. a reaction between the substrate and the solvent medium) is shown in Table 10.2. The... 

A az, s ) and solvent (k, s ) to a carbocation intermediate of solvolysis are first determined from the ratio of the yields the azide ion and solvent adducts (equation (1)). The value for may then be calculated from this product rate constant ratio M ), and az = 5 X 10 s for the diffusion limited... 

Fig. 1 for stepwise solvolysis of R-X is due to the increase in ks (s ), with decreasing stability of the carbocation intermediate, relative to the constant value of az (M s ) for the diffusion-limited addition of azide anion. The lifetime for the carbocation intermediate eventually becomes so short that essentially no azide ion adduct forms by diffusion-controlled trapping, because addition of solvent to R occurs faster than escape of the carbocation from the solvent cage followed by addition of azide ion (k Now, the nucleophile adduct must form through a... 

Fig. 1 A hypothetical plot of azide ion selectivity (M ) against the reactivity of the carbocation intermediate of solvolysis of R-X in aqueous solution (Scheme 4). The descending limb on the left hand side of this plot is for reactions where the value of ks(s ) is increasing relative to the constant value of s ) for diffusion-limited addition of...

The difference between A obsd and caic might be due to a specific salt effect on the rate constant for solvolysis. However, this is unlikely because perchlorate ion acts to stabilize carbocations relative to neutral substrates.At high concentrations of sodium bromide, the rate-limiting step for solvolysis of 1-Br is the capture of 1 by solvent (ks Scheme 5A). Substitution of Br for CIO4 should destabilize the carbocation-like transition state for this step relative to the starting neutral substrate, and this would lead to a negative, rather than positive deviation of obsd for equations (3A) and (3B). 

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