Isomerization of ion pair reaction intermediates

The observation of hidden reactions during solvolysis, through the use of chiral or isotopically labeled substrates has created considerable excitement in communities interested in the mechanisms of nonenzymatic15 and enzyme catalyzed reactions.38,39 These hidden reactions reveal something interesting about reaction mechanisms. However, chemists and biochemists are still working on the problem of extracting simple and definitive conclusions from analysis of data for these isomerization reactions. 

The solvolysis of MeS-4-0(S)CPh in aqueous/trifluoroethanol at 25 °C is zero-order in [N ].42 Fig. 4A shows that formation of MeS-4-N3 occurs at the expense of MeS-4-OSolv but not MeS-4-S(0)CPh. The reaction of MeS-4-(3,5-dinitrobenzoate) under the same conditions proceeds through the liberated carbocation intermediate MeS-4+ which partitions between addition of solvent to form MeS-4-OSolv and azide anion to form MeS-4-Nj.14 Fig. 4B shows that the yields of MeS-4-Nj, calculated as a fraction of the sum of the yields of MeS-4-Nj and MeS-4-OSolv, from the reactions of MeS-4-0(S)CPh and MeS-4-(3,5-dinitrobenzoate) are identical. These data show that essentially 100% of the ion-pair intermediate of reaction of MeS-4-(3,5-dinitrobenzoate) undergoes separation to the free carbocation which is trapped by azide ion, while 14% of the reaction of MeS-4-0(S)CPh proceeds by this pathway and 86% proceeds by the competing isomerization reaction.42 

The rate constants for addition of solvent to X-4+ approach the value of k, 1011 s 1, so that the ion pair reaction intermediate will undergo addition of 

We have examined the competing isomerization and solvolysis reactions of 1-4-(methylphenyl)ethyl pentafluorobenzoate with two goals in mind 52 (1) We wanted to use the increased sensitivity of modern analytical methods to extend oxygen-18 scrambling studies to mostly aqueous solutions, where we have obtained extensive data for nucleophilic substitution reactions of 1-phenylethyl derivatives. (2) We were interested in comparing the first-order rate constant for internal return of a carbocation-carboxylate anion pair with the corresponding second-order rate constant for the bimolecular combination of the same carbocation with a carboxylate anion, in order to examine the effect of aqueous solvation of free carboxylate anions on their reactivity toward addition to carbocations. 

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A Global scheme for solvolysis 2 Clocks for reactions of ion pairs 3 Addition of solvent to carbocation-anion pairs i Protonation of a carbocation-anion pair 11 Isomerization of ion pair reaction intermediates Reorganization of ion pairs in water 13 Internal return of isotopically labeled ion pairs Racemization of ion pairs 22 Concluding remarks 24 Acknowledgements 24 References 24... 

Much is known about the lifetimes of carbocation intermediates of solvolysis, and these data have proven critical in the design of experiments to estimate absolute rate constants for reorganization of ion pairs. Consider reorganization of an ion-pair reaction intermediate that exchanges the positions of the nucleophilic atoms of the leaving group (, Scheme 9) and that occurs in competition with diffusional separation to free ions (k-d) which is much faster than addition of solvent to the ion pair. Ion-pair separation is irreversible and will result in formation of solvolysis reaction products s ). Reorganization of the ion pair will result in formation of isomerization reaction product and the yield of this reaction product will provide a measure of the relative rate constant... 

Solvolysis and isomerization may either proceed through a common ion-pair reaction intermediate, or the isomerization reaction may proceed by a separate concerted reaction pathway that avoids formation of this intermediate kcon Scheme 10). Hammett reaction constants of = —4.9 and pjt = —5.5 for reactions of X-4-0(S)CPb were calculated from the data in Table 1. The larger negative value... 

Equation (16) gives the relationship between the rate constant ratio iso = 0.53 and the rate constants from Scheme 15 for partitioning of the ion pair reaction intermediate. Racemization and isomerization will proceed at similar rates, if inversion of the ion pair is much faster than the other reactions... 

Thus, fluorination of 1,3-dienes proceeds through an allylic ion, while weakly bridged halonium ions are the intermediates in chlorination and bromination of dienes (vide infra). Furthermore, starting from the experimental evidence that 13 is produced under kinetic conditions and not from subsequent rearrangement of the 1,2- and 1,4-adducts, the authors suggested that 13 arose from rearrangement of the allyl cation intermediate, 17. Consistent with an open ion pair intermediate is also the stereoselective formation of the threo isomer from both 1,3-pentadienes, as well as the preference for the addition to the 1,2-bond observed in the reaction of both isomeric pentadienes. This selectivity may indeed... 

Scheme 12 shows a minimal mechanism for solvolysis and isomerization of Me-4- 0C(0)QF5. Values of = 6 X 10 s for the direct nucleophilic addition of solvent to the ion-pair intermediate, and k- = 1.6 X 10 s for the irreversible diffusional separation of the intermediate to free ions have been reported in earlier work. Both of these reactions result, eventually, in formation of the solvent... 

Fig. 7.11 Reaction profiles for L-catalyzed isomerization of cis-to-trans ML2X2. In (A) an ionic intermediate is favored by a polar solvent. In (B) ion-pair formation arises with a less polar solvent. In (C) a non-polar solvent promotes a 5-coordinated intermediate. In (C), pseudo-rotation occurs. Based on D. G. Cooper and J. Powell, J. Amer. Chem. Soc. 95, 1102 (1973) see also Ref. 90. Reproduced with permission from D. G. Cooper and J. Powell, J. Amer. Chem. Soc. 95, 1102 (1973). (1973) American Chemical Society.

Other Reactions of Olefinic Steroids.—Reaction of cholest-5-en-3-one with air and acetic acid shows that isomerization to the A -3-oxo-compound is accompanied by autoxidation to the 6a- and 6/8-hydroxy-3-oxo-A -compounds and the 3,6-dioxo-A -compound. The oxidation appears to be controlled by heterolysis of the 4/3-proton and formation of the intermediate ion pair (73). Sitosterol was autoxi-dized at C-7 to give the 7-oxo- and the epimeric 7-hydroxy-derivatives. Oxidation of a 17-methylene steroid with Pb, Tl" , and Hg acetates in methanol gave a wide variety of products. The reaction with Pb(OAc)4 gave the rearranged products (74), (75), and (76) whereas the Tl and Hg products retained the... 

The azomethine-azomethine isomerization of 14 to 15 proceeds essentially intramolccular-ly (> 98 %), as shown by the reaction of ketimine 14h in a solution of triethylamine/methanol-r/4 (1 1), which gives 15h in 93% yield with less than 2% incorporation of deuterium in the product.14 The intermediate 2-azaallyl anion 12 apparently exists as a contact ion pair. 

The addition of HX to double bonds in the dark and in the absence of free-radical initiators is closely related to hydration The orientation of the elements of HX in the adduct always rnrrrsponds to Markownikoff addition 16 no deuterium exchange wish solvent is found in unreacted olefins recovered after partial reaction, nor is recovered starting material isomerized after partial reaction.17 However. the addition of HX apparently can proceed by a number of different mechanisms depending on the nature Ol the substrate and on the reaction conditions. Thus when HC1 is added to f-butylethylene in acetic acid, the rate is first-order in each reactant and the products are those shown in Equation 7.5.le Since 4 and 6 were demonstrated to be stable to the reaction conditions, the rearranged product (5) can be formed only if a carbocationic intermediate is formed during reaction. However, the carbocation exists almost solely in an intimate ion pair, and the rate of collapse of the ion pair to products must be faster than, or comparable to, the rate of diffusion of Cl- away from the carbocation. This must be so because the ratio of chloride to acetate products is unaffected by... 

In the case of the disilanyldiazoacetate 303, photolysis initially gives the carbene 304 that rearranges to the silaacrylate 305165, which then isomerizes to the bissilylketene 306 (equation 77). The trapping reaction with alcohols gives the products 307 and 308. The latter is obviously formed via ion pair intermediates like 309. The UV and IR spectra of irradiated matrices at 10 K have been measured. The band at 1670 cm-1 is tentatively assigned to the vc=o of 305 Xmax is at 288 nm. 

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