Substitution Versus Elimination Reactions

Effect of Solvent on Elimination versus Substitution. Increasing polarity of solvent favors Sn2 reactions at the expense of E2. In the classical example, alcoholic KOH is used to effect elimination, while the more polar aqueous KOH is used for substitution. Charge-dispersal discussions, similar to those on page 450, only partially explain this. In most solvents, SnI reactions are favored over El. The El reactions compete best in polar solvents that are poor nucleophiles, especially dipolar aprotic solvents" A study made in the gas phase, where there is no solvent, has shown that when 1-bromopropane reacts with MeO only elimination takes place no substitution even with this primary substrate." ... 

Then the differences in rate caused by the electronic effect of the substituent are correlated by the Hammett equation log(kz/kH) = poz, where kz is the rate constant obtained for a compound with a particular meta or para substituent, ku is the rate constant for the unsubstituted phenyl group, and crz is the substituent constant for each substituent used. The proportionality constant p relates the substituent constant (electron donating or wididrawing) and the substituent s effect on rate. It gives information about the type and extent of charge development in the activated complex. It is determined by plotting log(kz/kQ) versus ov for a series of substituents. The slope of the linear plot is p and is termed the reaction constant. For example, the reaction shown above is an elimination reaction in which a proton and the nosy late group are eliminated and a C-N n bond is formed in their place. The reaction is second order overall, first order in substrate, and first order in base. The rate constants were measured for several substituted compounds ... 

The competing /3-hydrogen elimination and oxidative substitution of the acetoxyalkylpalladium(II) intermediate bear many similarities to the competing oxidative elimination and oxidative substitution mechanisms observed in electron transfer reactions of alkyl radicals with Cu(II) complexes.633,64 An alternative explanation for the competing pathways in the decomposition of the acetoxyalkylpalladium(II) intermediate can be represented by oxidative elimination versus 1-electron transfer followed by a subsequent electron or ligand transfer, that is,... 

Examples of the solvent-dependent competition between nucleophilic substitution and / -elimination reactions [i.e. SnI versus Ei and Sn2 versus E2) have already been given in Section 5.3.1 [cf. Table 5-7). A nice example of a dichotomic y9-elimination reaction, which can proceed via an Ei or E2 mechanism depending on the solvent used, is shown in Eq. (5-140a) cf. also Eqs. (5-20) and (5-21) in Section 5.3.1. The thermolysis of the potassium salt of racemic 2,3-dibromo-l-phenylpropanoic acid (A), prepared by bromine addition to ( )-cinnamic acid, yields, in polar solvents [e.g. water), apart from carbon dioxide and potassium bromide, the ( )-isomer of l-bromo-2-phenylethene, while in solvents with low or intermediate polarity e.g. butanone) it yields the (Z)-isomer [851]. 

Effect on Elimination versus Substitution. As we have already seen (p. 1487), for first-order reactions the leaving group has nothing to do with the... 

Grignard reagents can be made to react with aromatic rings under appropriate conditions. Both addition and substitution are observed, and the mixture of products depends on the reaction conditions, substitution being the result of addition, followed by elimination [1,27]. The factors affecting 1,2- versus 1,4-addition for hindered aryl ketones (leading to ring-alkylated products) have been reviewed by Fuson [28]. 

Section 4 emphasized the need to ensure a bimolecular mechanism if we are to control the amount of elimination versus substitution (and vice versa). Reaction of Compound 4.2 with sulfuric acid proceeds via an El mechanism... 

Catalytic hydrogenation reactions, like those shown above, are a type of addition teac-tion (versus substitution or elimination), and they are also a type of reduction. This leads to a distinction between compounds that are saturated versus those that are unsaturated. 

Secondary halides are borderline, and substitution or elimination may be favored, depending on the particular base/nucleophile, solvent, and temperature at which the reaction is carried out. Elimination is favored with strong bases/good nucleophiles—for example, hydroxide ion and ethoxide ion. Substitution is favored with weak bases/poor nucleophiles—for example, acetate ion. Table 7.7 summarizes these generalizations about substitution versus elimination reactions of haloalkanes. 

For a secondary halide in a reaction with a base, with water as the solvent, ionization is a competitive process. Most of the time, the 8 2 is faster than the Sf fl reaction because direct attack at the a-carbon is more facile than ionization, but the extent of direct substitution versus ionization and then trapping with a nucleophile depend on the strength and nature of the nucleophile. If the nucleophile is a weak base, the Sn2 reaction will dominate in an aprotic solvent. If the nucleophile is a strong base, elimination competes with substitution, and a mixture of Sn2 and E2 products is predicted. In water, it is not obvious whether ionization will lead to the major product, although it is assumed that in aqueous media the 8 1 reaction will dominate. 

Almost all bases are also nucleophiles, and hence we expect competition between eliminations and substitutions. In both Sn2 and E2 reactions, the nucleophile or base reacts in a single rate-determining step with the reactant. In both SnI and El reactions, the nucleophile or base reacts in a step after the rate-determining heterolysis. Because the experimental observations for substitution and elimination reactions are so similar, we leave the discussion of kinetics to our discussion of substitutions in the next chapter. There are, however, some points that we should make about the factors that influence the extent of 5 2 versus E2 and SmI versus El reactions (Eq. 10.69). 

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