Elimination—addition Elcb mechanism

Williams and his coworkers have shown that the hydrolysis and aminolysis of aryl toluene-a-sulphonates proceed via a stepwise elimination-addition (ElcB) mechanism (equation 101)137 139. 

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). 

A dissociative elimination-addition pathway has also been proposed to account for the kinetics of alkaline hydrolysis of 2,4-dinitrophenyl 4 -hydroxyphenylpropionitrile in 40% (v/v) dioxane-water, although participation of the associative Bac2 mechanism cannot be ruled out since it may be facilitated by the electronic effect of the triple bond. Formation of intermediate (15), having a conjugated and cumulated double-bond system, should favour the ElcB mechanism and thereby account for the contrasting entropies of activation found for hydrolysis of (14) and the corresponding 4 -methoxyphenylpropionate. 

In certain cases in which the substrate carries an a hydrogen, there is strong evidence1728 that at least some of the reaction takes place by an elimination-addition mechanism (ElcB, similar to the one shown on p. 382), going through a sulfene intermediate,1729 e.g., the reaction between methanesulfonyl chloride and aniline. 

An attempt to study resolved (( )-18) as a probe for the detailed mechanism of the Adn—E vinylic substitution reaction has been complicated by intervention of a competing reaction route this is believed to involve a competing (ElcB elimination-addition, for which antiperiplanar orientation of H and Cl is not a requirement.7 a-Deuterated (ca 50%) E- and Z-substitution products (which do not themselves exchange deuterium) are obtained on reaction with MeS in 9 1 CD3CN-D2O but no incorporation of deuterium in unreacted ((/r)-18) occurs and neither does isomerism to ((Z)-18) precede elimination. 

For N-alkyl or N-aryl /3-lactams, substitution at the 4-position must involve either elimination-addition via an azetinone containing a 3.4 carbon-carbon double bond (7—>8—>9) or direct displacement by SN2 (7— 9) or SN1 (7—>10—>9) mechanisms. The elimination-addition pathway would again presumably occur by an ElcB mechanism, but with anion formation now occurring at the 3- rather than the I-position (90JOC3244). 

The results are consistent with a preliminary base-catalysed fast reversible equilibration of the a-hydrogen leading to exchange. Concurrent attack of the base at the -carbon competes with trans elimination to acetylene, and exchange could be observed for either mechanism, or even in the absence of substitution (Scheme 7). With a weaker base, e.g. PhS-, the exchange is slower than substitution. The trans isomer favours addition-elimination, while the cis isomer reacts, at least partially, via the acetylenic intermediate, showing an element effect. The absence of an isotope effect suggests an ElcB mechanism. 

This elimination is catalyzed by the enzyme enolase and follows an Elcb mechanism. The enzyme supplies a base to remove the acidic proton and generate a carbanion in the first step. In addition, a Mg2+ cation in the enzyme acts as a Lewis acid and bonds to the hydroxy group, making it a better leaving group. 

Fig. 10.46. Mechanism of a Knoevenagel reaction with nitromethane. Alkaline aluminum oxide powder is sufficiently basic to deprotonate nitromethane. The small amount of the anion generated from nitromethane suffices for the addition to aldehydes to proceed. The elimination of water via an Elcb mechanism follows quickly if a conjugated C=C double bond is formed, as in the present case.

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. 1488). 

The second step involves an elimination of the tertiary amine (ElcB mechanism) and a coniac. addition of the enolate anion of diethyl malonate to the resulting enone. This device prevent v reactive enone from combining with itself by releasing it only in the presence of an excess c -.ii nucleophile. 

Substitution by the SN2 mechanism and -elimination by the E2 and Elcb mechanisms are not the only reactions that can occur at C(sp3)-X. Substitution can also occur at C(sp3)-X by the SRN1 mechanism, the elimination-addition mechanism, a one-electron transfer mechanism, and metal insertion and halogen-metal exchange reactions. An alkyl halide can also undergo a-elimination to give a carbene. 

An elimination-addition mechanism can be proposed. MeO- is both a good nucleophile and a good base. It can induce / -elimination of HBr (probably by an Elcb mechanism, because of the nonperiplanar relationship between the C-H and C-Br bonds) to give a compound that is now is-electrophilic at the C atom that was formerly a-electrophilic. Another equivalent of MeO- can now undergo conjugate addition to the electrophilic C atom the addition occurs from the bottom face for steric reasons. Proton transfer then gives the observed product. 

The intermediate of the ElcB mechanism is a carbanion, and thus any factors that stabilise such an ion should favour this mechanism. We have already noted above that on the face of it, elimination reactions are the reverse of addition reactions. However, we also noted that the actual mechanistic pathways involved in elimination reactions were more similar to substitution reactions than addition reactions. This is because normally elimination reactions proceed via a carbonium ion or in a single step that has certain similarities to an SN2 substitution reaction. However, there are also addition reactions that proceed via a carbanion intermediate, for example the Michael-type reaction, in which a carbanion adds to an a,(3-unsaturated carbonyl compound. Indicate the Michael-type addition between the anion formed from the diester of propandioic acid (or malonic acid) and 2-butenal. 

The ElcB mechanism is rare in practice when the elimination reaction would result in a carbon/carbon double bond. When a carbon/oxygen double bond is to be formed then it is far more common. For example, the ElcB mechanism is found in the reverse of the cyanohydrin formation reaction. You will recall that the forward reaction involves the addition of a cyanide anion to a carbonyl group. Write down the pathway for the reverse reaction, i.e. the elimination reaction. 

Classify each step or group of steps as a proton transfer, substitution, elimination, addition, or rearrangement. Then check for other alternative forms of the same process that may fit the reaction conditions better. For example, your first impulse in a particular problem might be to write some sort of elimination because it seems to get you closer to the answer. If you recognize that what you need is a type of elimination, you would know that eliminations could go by El, E2, ElcB, or Ei mechanisms. You can then pick the most appropriate one, rather than remaining with the first one that occurred to you. 

VII. j3-Elimination-Addition Reactions E2 versus ElcB Mechanisms. 397... 

Similar observations of base catalysis have been used to invoke the ElcB mechanism for elimination from 4,4-dicyano-3-p-nitrophenyl-1 -phenylbutan-1 -one in neutral and acidic methanol (34) , and l,l,l,3-tetranitro-2-phenylpro-pane in methanol in the presence of hydrochloric acid and pyridine-pyridine hydrochloride buffers (36) . In the former reaction, an example of a reverse Michael addition, the carbanion intermediate with the electron pair alpha to the carbonyl rather than in the gamma position is favoured, as the methyl isomer (35) eliminates more rapidly than the parent compound. 

The mechanism for an aldol condensation has two parts (Mechanism 22.6). The first part is just an aldol addition reaction, which has three mechanistic steps. The second part has two steps that accomplish the elimination of water. Normally, alcohols do not undergo dehydration in the presence of a strong base, but here, the presence of the carbonyl group enables the dehydration reaction to occur. The a position is first deprotonated to form an enolate ion, followed by expulsion of a hydroxide ion to produce a,p unsaturation. This two-step process, which is different from the elimination reactions we saw in Chapter 8, is called an Elcb mechanism. In an Elcb mechanism, the leaving group only leaves after deprotonation occurs. 

The transition states of the E2 and ElcB mechanisms are represented in Fig. 37.3 together with the KIEs that should be observed in each case. Just by comparing the three transition states, it becomes clear that no primary D KIE should be observed in the (E1cB)r mechanism, as the proton has been already removed. As the experimental fact is a clear primary D KIE at C3, the EIcBr mechanism must be discarded. Additionally it is an experimental fact that no H/D exchange with the solvent has been observed in the elimination of substrates 1. Solvent H/D exchange is indicative for an EIcBr mechanism where the carbanion is reprotonated by the solvent in the fast initial step (see equation C in Scheme 37.2). 

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