ElcB mechanisms

We will discuss shortly the most important structure-reactivity features of the E2, El, and Elcb mechanisms. The variable transition state theoiy allows discussion of reactions proceeding through transition states of intermediate character in terms of the limiting mechanistic types. The most important structural features to be considered in such a discussion are (1) the nature of the leaving group, (2) the nature of the base, (3) electronic and steric effects of substituents in the reactant molecule, and (4) solvent effects. 

There is another useiiil way of depicting the ideas embodied in the variable transition state theory of elimination reactions. This is to construct a three-dimensional potential energy diagram. Suppose that we consider the case of an ethyl halide. The two stepwise reaction paths both require the formation of high-energy intermediates. The El mechanism requires formation of a carbocation whereas the Elcb mechanism proceeds via a caibanion intermediate. 

For compounds in which hydrogen is sufficiently acidified by enough fluorines in (3 positions, the ElcB mechanism may be operating [II]... 

Dehydrofluorination of compounds in which a single hydrogen is flanked by heavily fluonnated groups is achieved by aqueous or alcoholic alkali hydroMdes and proceeds probably by the ElcB mechanism Thus 1 -(2//-hexafluoropropyl)ada-mantane [75] and 1,3 bis(2//hexafluoropropyl)adamantane [16] sire dehydro-fluorinated in respective yields of 75 and 81% (equation 14)... 

Elimination of hydrogen halides from polyfluoroalkanes by bases also usually involves earbanion intermediates (ElcB mechanism) [<8/l, and orientation is there tore governed by relative C H acidities and leaving group mobility Some examples are shown in equations 16-18 [145]... 

It has been noticed that the reverse reaction of Eq. (5) is a particular type of the Hofmann elimination reaction (26) via either an E2 or an ElcB mechanism. An E2 mechanism seems to be more obvious for this reaction than an ElcB mechanism, however. 

If however a t-butoxide was used as base, only the thermodynamically favored S-alkene 9 was formed, suggesting a ElcB-mechanism in that case. It has... 

All three elimination reactions--E2, El, and ElcB—occur in biological pathways, but the ElcB mechanism is particularly common. The substrate is usually an alcohol, and the H atom removed is usually adjacent to a carbonyl group, just as in laboratory reactions. Thus, 3-hydroxy carbonyl compounds are frequently converted to unsaturated carbonyl compounds by elimination reactions. A typical example occurs during the biosynthesis of fats when a 3-hydroxybutyryl thioester is dehydrated to the corresponding unsaturated (crotonyl) thioester. The base in this reaction is a histidine amino acid in the enzyme, and loss of the OH group is assisted by simultaneous protonation. 

In the ElcB reaction, C-H bond-breaking occurs first. A base abstracts a proton to give an anion, followed by loss of the leaving group from the adjacent carbon in a second step. The reaction is favored when the leaving group is two carbons removed from a carbonyl, which stabilizes the intermediate anion by resonance. Biological elimination reactions typically occur by this ElcB mechanism. 

As noted previously in Section 11.10, biological dehydrations are also common and usually occur by an ElcB mechanism on a substrate in which the -OH group is two carbons away from a carbonyl group. An example occurs in the biosynthesis of the aromatic amino acid tyrosine. A base first abstracts a proton from the carbon adjacent to the carbonyl group, and the anion intermediate... 

StepS 9-1° of F Sure 29-7 Dehydration and Dephosphorylation Like mos /3-hydroxy carbonyl compounds produced in aldol reactions, 2-phospho glvcerate undergoes a ready dehydration in step 9 by an ElcB mechanism (Section 23.3). The process is catalyzed by enolase, and the product i... 

This mechanism does not apply to unsubstituted or N,N-disubstituted aryl carbamates, which hydrolyze by the normal mechanisms. Carboxylic esters substituted in the a position by an electron-withdrawing group (e.g., CN or COOEt) can also hydrolyze by a similar mechanism involving a ketene intermediate. These elimination-addition mechanisms usually are referred to as ElcB mechanisms, because that is the name given to the elimination portion of the mechanism (p. 1308). 

In the El mechanism, X leaves first, and then H. In the E2 mechanism, the two groups leave at the same time. There is a third possibility the H leaves first, and then the X. This is a two-step process, called the ElcB mechanism, or the carbanion mechanism, since the intermediate is a carbanion ... 

Of the three cases of the ElcB mechanism, the one most difficult to distinguish from E2 is (ElcB)i. One way to make this distinction is to study the effect of a change in leaving group. This was done in the case of the three acenaphthylenes (12), where it was found that (1) the three rates were fairly similar, the largest being only about four times that of the smallest, and (2) in... 

There is evidence that some ElcB mechanisms can involve carbanion ion pairs,... 

Still another method measures volumes of activation. These are negative for E2 and positive for ElcB mechanisms. Measurement of the activation volume therefore provides a continuous scale for deciding just where a reaction lies on the spectmm. 

In the ElcB mechanism the question of orientation seldom arises because the mechanism is generally found only where there is an electron-withdrawing group in the P position, and that is where the double bond goes. 

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