Isopropyl solvolysis

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-... 

Leffek, Llewellyn and Robertson (1960a, b) made careful conductometric determinations of deuterium kinetic isotope effects on the solvolysis rates (in water) of some ethyl, isopropyl and n-propyl sulphonates and halides. In the case of the n-propyl compoimds,... 

Deuterium isotope effects have been found even where it is certain that the C—H bond does not break at all in the reaction. Such effects are called secondary isotope effectsf" the term primary isotope effect being reserved for the type discussed previously. Secondary isotope effects can be divided into a and P effects. In a P secondary isotope effect, substitution of deuterium for hydrogen p to the position of bond breaking slows the reaction. An example is solvolysis of isopropyl bromide ... 

As a result of the inductive and hyperconjugative effects it is to be expected that tertiary carbonium ions will be more stable than secondary carbonium ions, which in turn will be more stable than primary ions. The stabilization of the corresponding transition states for ionization should be in the same order, since the transition state will somewhat resemble the ion. Thus the first order rate constant for the solvolysis of tert-buty bromide in alkaline 80% aqueous ethanol at 55° is about 4000 times that of isopropyl bromide, while for ethyl and methyl bromides the first order contribution to the hydrolysis rate is imperceptible against the contribution from the bimolecular hydrolysis.217 Formic acid is such a good ionizing solvent that even primary alkyl bromides hydrolyze at a rate nearly independent of water concentration. The relative rates at 100° are tertiary butyl, 108 isopropyl, 44.7 ethyl, 1.71 and methyl, 1.00.218>212 One a-phenyl substituent is about as effective in accelerating the ionization as two a-alkyl groups.212 Thus the reactions of benzyl compounds, like those of secondary alkyl compounds, are of borderline mechanism, while benzhydryl compounds react by the unimolecular ionization mechanism. 

The present procedure9 represents another synthesis of cyelobutanone through the unique acetylenic bond participation in solvolysis. Cyclobutane derivatives prepared in this way include 2-methyl-, 2-ethyl-, 2-isopropyl-, and 2-trifluoromethylcyclobutanone from the corresponding acetylenic compounds.10... 

Use of other methods has contributed further to the emerging picture of solvolysis of most secondary systems as being solvent-assisted. For example, the solvolysis rate acceleration on substituting a-hydrogen by CH3 in 2-adamantyl bromide is 107 5, much larger than that found for other secondary—tertiary pairs such as isopropyl-/-butyl. In molecules less hindered than 2-adamantyl, the secondary substrate is accelerated by nucleophilic attack of solvent.100 Rate accelerations and product distributions found on adding azide ion to solvolysis mixtures (Problem 4) also provide confirmatory evidence for these conclu-... 

Solvolysis rates of isopropyl tosylate and 2-adamantyl tosylate (28, p. 243) in 80 percent ethanol are measured with and without added azide. Define rate enhancement, R.E., as the ratio of rate with azide to rate without, and designate by /bn3 the fraction of alkyl azide in the product. Explain the significance of the fact that the isopropyl results fit the equation... 

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). 

It is interesting that for the different compounds in Table 21 AE/R has roughly the same value. We have also included the values for the solvent isotope effect for the solvolysis of isopropyl bromide. Heppolette and Robertson (1961) made an extensive study of the temperature variation of the solvent isotope effect for this compound. It can be seen that the values for isopropyl bromide match those of the other bromo compounds. The data for isopropyl bromide correlate well with the relative fluidities of HzO and D20 (Heppolette and Robertson, 1961) but this may arise because the AE/R values for the solvent isotope effect and for the relative fluidities happen by chance to be roughly equal. What is clear is that changing the group R has very little effect on the solvent isotope effect once one has allowed for the different temperatures at which the reactions are measured. This means that the solvent isotope effect for the solvolysis of halides is caused either by the LzO sites on the nucleophile having much the same fractionation factors or by the dynamic medium effect or by a combination of both. 

Fig. 22 The location of transition states for reactions of isopropyl compounds. The points are for solvolysis reactions. The bar shows the location for the reactions in Table 28.

Further support for this interpretation can be found by considering the data for the hydrolysis of isopropyl compounds in Table 28. The values of r are calculated from (112). It can be seen that the transition states for the isopropyl transfers are much looser than those for the methyl transfers. The solvolysis of isopropyl compounds is closer to the borderline between the SN1 and SN2 mechanisms and therefore we may expect the SN2 transition state to be looser. As discussed above there is supporting evidence from Ko and Parker s (1968) measurements of transfer activity coefficients for the transition state. 

Irimethylsilyl /j-keto carboxylate (3) in 70% yield. The -kelo acid (4) is obtained in quantitative yield by solvolysis with methanol. Pyrolysis of (4) yields fert-butyl isopropyl ketone (5), again in quantitative yield. 

The kgjko isotope effect for the solvolysis of chloromethyl methyl ether in isopropyl alcohol at 0° is 1.24 + 0.08 per deuterium atom " . This is in the range of other unimolecular reactions. The values of and AS for the chloroether in isopropyl alcohol are 10.7 0.6 kcal.mole" and —28.8 + 1.6 eu, respectively. In contrast, the corresponding values for solvolysis of alkyl chlorides are in the range of about 20-25 kcal.mole and —4 to —12 eu. The lower values of A/f and AS for the solvolysis of chloromethyl methyl ether are tentatively attributed to the double bond character between oxygen and carbon at the transition state (see above) . 

Okamoto, Y., Inukai, T. and Brown, H.C. (1958c). Rates of Solvolysis of Phenyldimethylcarbinyl Chlorides in Methyl, Ethyl and Isopropyl Alcohols. Influence of the Solvent on the Value of the Electrophilic Substituent Constant. J.Am.Chem.Soc., 80,4972-4976. 

The solvolysis of isopropyl halides is generally considered to occur near the mechanistic border-line which marks the beginning of entirely Sul reaction, like the solvolysis of benzyl halides. Results relevant to the present discussion are available only for reaction with water and have been included with those for other Su2 processes in Table 6 since AC is less negative than would have been expected for entirely Sul solvolysis no complicating features which might reverse this conclusion have been envisaged. 

Isopropyl chloride and bromide show values of JjS which are intermediate between those found for the corresponding primary and tertiary compounds, unlike benzyl halides whose solvolytic behaviour is close to that of n-alkyl halides (see Tables 5, 6). This suggests that the solvolysis of isopropyl halides occurs by a process which is not uni-molecular but nevertheless shows more of the features of reaction by... 

The solvolysis of isopropyl p-toluenesulphonate in 50% aqueous acetone shows a value of ACp JAS which is very close to that observed for established reactions and the same mechanism can therefore be assumed. However, a different conclusion is required when the solvent is 85% acetone, a poorer ionising medium, since AC I AS is now a little smaller than would have been expected (see Table 10). These observations and their interpretation are fully consistent with solvolysis near the mechanistic border-line. Completely Sj l solvolysis should therefore also occur in water but the validity of this conclusion cannot be definitely established since AC appears to be independent of mechanism in the solvolysis of sulphonates (see Section IVC4). However, for the hydrolysis of isopropyl methanesulphonate and benzenesulphonate in water is about 10 caldeg. greater than for the Sjj2 reactions of the primary compounds, a difference often found between S l and Sif2 solvolysis, but isopropyl -toluenesulphonate is clearly anomalous (see Table 6). 

Fig. 9. Absence of a free-energy correlation for the solvolysis of isopropyl tosylate in representative solvents. I Reproduced from Brown, H. C. The nonclassical ion problem. New York Plenum Press 1977.1...

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