Reactivity - Lesson 2 - Aliphatic, Alkenyl, and Alkynyl Substitution, Electrophilic and Organometallic - Introduction - March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 7th Edition (2013)

Part II. Introduction

Chapter 12. Aliphatic, Alkenyl, and Alkynyl Substitution, Electrophilic and Organometallic

12.B. Reactivity

Only a small amount of work has been done in this area, compared to the vast amount done for aliphatic nucleophilic substitution and aromatic electrophilic substitution. Therefore, only a few conclusions can be drawn, most of them sketchy or tentative.38

1. Effect of Substrate. For SE1 reactions, electron-donating groups decrease rates and electron-withdrawing groups increase them. This is expected for a reaction in which the rate-determining step is analogous to the cleavage of a proton from an acid. For the SE2 (back) mechanism, Jensen and Davis12 showed that the reactivity of alkyl groups is similar to that for the SN2 mechanism (i.e., Me > Et > Pr > iPr > neopentyl), as is expected, since both involve backside attack and both are equally affected by steric hindrance. In fact, this pattern of reactivity can be regarded as evidence for the occurrence of the SE2 (back) mechanism in cases where stereochemical investigation is not feasible.39 For SE2 reactions that proceed with retention, several studies have been made with varying results, depending on the reaction.40 One such study, which examined the reaction RHgBr + Br2 → RBr catalyzed by Br, gave the results shown in Table 12.1.41 This data shows that branching increased the rates, while β branching decreased them. Sayre and Jensen41 attributed the decreased rates to steric hindrance, although attack here was definitely frontside, and the increased rates to the electron-donating effect of the alkyl groups, which stabilized the electron-deficient transition state.42 Of course, steric hindrance should also be present with the a branched groups, so these workers concluded that if it were not, the rates would be even greater. The Br electrophile is a rather large one and it is likely that smaller steric effects are present with smaller electrophiles. The rates of certain second-order substitutions of organotin compounds have been found to increase with increasing electron withdrawal by substituents. This behavior has been ascribed43 to an SE2 mechanism involving ion pairs, analogous to Sneen's ion-pair mechanism for nucleophilic substitution (Sec. 10.A.iv). Solvolysis of 2-bromo-1,1,1-trifluoro-2-(p-methoxyphenyl)ethane in water proceeds via a free carbocation intermediate, but ion pairing influences the reaction in the presence of bromide ion.44

2. Effect of Leaving Group. For both SE1 and second-order mechanisms, the more polar the C–X bond, the easier it is for the electrofuge to cleave. For metallic leaving groups in which the metal has a valence >1, the nature of the other group or groups attached to the metal thus has an effect on the reaction. For example, consider a series of organomercurials (RHgW). Because a more electronegative W decreases the polarity of the C–Hg bond and furthermore results in a less stable HgW+, the electrofugal ability of HgW decreases with increasing electronegativity of W. Thus, HgR′ (from RHgR′) is a better leaving group than HgCl (from RHgCl). Also in accord with this is the leaving-group order Hg–t-Bu > Hg–iPr > HgEt > HgMe, reported for acetolysis of R2Hg,42 since the more highly branched alkyl groups better help to spread the positive charge. It might be expected that, when metals are the leaving groups, SE1 mechanisms would be favored, while with carbon leaving groups, second-order mechanisms would be found. However, the reported results have been just about the reverse of this. For carbon leaving groups the mechanism is usually SE1, while for metallic leaving groups the mechanism is almost always SE2 or SEi. A number of reports of SE1 reactions with metallic leaving groups have appeared,45 but the mechanism is not easy to prove and many of these reports have been challenged.46 Reutov and co-workers45 expressed the view that in such reactions a nucleophile (which may be the solvent) must assist in the removal of the electrofuge and refer to such processes as SE1(N) reactions.

3. Effect of Solvent. 47 In addition to the solvent effects on certain SE1 reactions mentioned earlier (Sec. 12.A.ii), solvents can influence the mechanism that is preferred. As with nucleophilic substitution (Sec. 10.G.iv), an increase in solvent polarity increases the possibility of an ionizing mechanism, in this case SE1, in comparison with the second-order mechanisms, which do not involve ions. As previously mentioned (Sec. 12.A.ii), the solvent can also exert an influence between the SE2 (front or back) and SEi mechanisms in that the rates of SE2 mechanisms should be increased by an increase in solvent polarity, while SEi mechanisms are much less affected.

Table 12.1 Relative Rates of the Reaction of RHgBr with Br2 and Bra

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