E2 process

Effects that arise because one spatial arrangement of electrons (or orbitals or bonds) IS more stable than another are called stereoelectronic effects There is a stereoelec tromc preference for the anti coplanar arrangement of proton and leaving group in E2 reactions Although coplanarity of the p orbitals is the best geometry for the E2 process modest deviations from this ideal can be tolerated In such cases the terms used are syn periplanar and anti periplanar... 

As a practical matter elimination can always be made to occur quantitatively Strong bases especially bulky ones such as tert butoxide ion react even with primary alkyl halides by an E2 process at elevated temperatures The more difficult task is to find condifions fhaf promofe subsfifufion In general fhe besf approach is fo choose condi lions lhal favor fhe 8 2 mechanism—an unhindered subslrale a good nucleophile lhal IS nol slrongly basic and fhe lowesl praclical lemperalure consislenl wilh reasonable reaclion rales... 

AJkynes can be made by dehydrohalogenation of vinylic halides in a reaction that is essentially an E2 process. In studying the stereochemistry of this elimination, it was found that (Z)-2-chloro-2-butenedioic acid reacts 50 times as fast as the corresponding isomer. What conclusion can you draw about the stereochemistry of eliminations in vinylic halides How does this result compare with eliminations of alkyl halides ... 

Mechanism of the dehydration of secondary and tertiary alcohols by reaction with POCI3 in pyridine. The reaction is an E2 process. 

In an E2 process, a base removes a proton, causing the simultaneous expulsion of a leaving group ... 

Now let s consider the effect of the substrate on the rate of an E2 process. Recall from the previous chapter that Sn2 reactions generally do not occur with tertiary substrates, because of steric considerations. But E2 reactions are different than Sn2 reactions, and in fact, tertiary substrates often undergo E2 reactions quite rapidly. To explain why tertiary substrates will undergo E2 but not Sn2 reactions, we must recognize that the key difference between substitution and elimination is the role played by the reagent. In a substitution reaction, the reagent functions as a nucleophile and attacks an electrophilic position. In an elimination reaction, the reagent functions as a base and removes a proton, which is easily achieved even with a tertiary substrate. In fact, tertiary substrates react even more rapidly than primary substrates. 

This is the Zaitsev product that we expect. The stereoisomer of this alkene is not prodnced, because the E2 process is stereospecific ... 

In a case like this, E2 wins the competition, and no other mechanisms can snccessfnlly compete. Why not An Sn2 process cannot occnr at a reasonable rate becanse the snbstrate is tertiary (steric hindrance prevents an Sn2 from occnrring). And nnimolecnlar processes (El and SnI) cannot compete becanse they are too slow. Recall that the rate-determining step for an El or SnI process is the loss of a leaving gronp to form a carbocation, which is a slow step. Therefore, El and SnI conld only win the competition if the competing E2 process is extremely slow (when a weak base is nsed). However, when a strong base is nsed, E2 occnrs rapidly, so El and SnI cannot compete. 

We expect the E2 pathway to predominate, because it is less sensitive to steric hindrance than the Sn2 pathway. Therefore, we would expect the major product(s) to be generated via an E2 process, and the minor product(s) to be generated via an Sn2 process. In order to draw the products, we must complete the third and final step. That is, we must consider the regiochemical and stereochemical outcomes for both the E2 and Sn2 processes. Let s begin with the E2 process. 

Next, look at the stereochemistry. The E2 process is stereoselective, so we expect cis and trans isomers, with a predominance of the trans isomer ... 

The E2 process is not only stereoselective, but it is also stereospecific. However, in this case, the p position has more than one proton, so the stereospecificity of this reaction is not relevant. 

In the last step, tert-butoxide was used to favor elimination over substitution (see Section 10.10). hi summary, we have seen that we can use either an El process or an E2 process to convert an alcohol into an alkene. 

The ratio of products (36) and (37) from VNS of hydrogen (Pe) and substimtion of halogen (Px), respectively (Scheme 4), will depend on the strength and concentration of base, provided that the elimination is a kinetically important step in the VNS reaction, namely Pr/Px = kikE[B]/k-ikx. The influence of base will decrease until a constant value Ph/Px = k /kx is reached as kslB] k i. This has been demonstrated for 4-chloronitrobenzene, which undergoes exclusive substimtion of chlorine unless strong base is present to favour the VNS process. The deuterium isotope effect for VNS hydroxylation by Bu OOH, determined as me ratio of H versus D substitution of l-deutero-2,4-dinitrobenzene, varied from 7.0 0.3 to 0.98 0.01 as the base in NH3 was changed from NaOH to Bu OK me former value is consistent with a rate determining E2 process. 

The treatment of the deuteriated cis oxirane 32 by EDA in HMPA yields exclusively the nondeuteriated alcohol 33. Indeed, complexation of the lithium cation by HMPA prevents the formation of the six-center transition state. The isomerization thus follows a more common E2 process, i.e. anti -elimination. 

The dehydration reaction leads by an E2 process to 8 and is promoted by the tertiary, benzylic nature of the OH group at Ce and its antiperiplanar trans relationship to the H atom at Csa-Furthermore, one of the cannonical forms of the enolizable 3-dicarbonyl system present at Cn and C12 has a double bond in the C ring. Thus, dehydration leads to aromatization of the C ring, and this factor must provide sane of the driving force for the reaction. 

It has been argued that the occurrence of isotope exchange at the p-carbon does not prove an EIcBr mechanism, only that a carbanion is formed under the reaction conditions—it is possible that an E2 process is responsible for product formation (i.e., ki > e2 > k2hlk-i In other words, the carbanion is formed and... 

Another method of seeking evidence of the EIcBirr mechanism is to exam heavy-atom isotope effects in the leaving group. Of course, these should be much more significant in an E2 process because the bond is breaking in the transition state. For example, Thibblin and co-workersfound that in the base-induced elimination of an alkyl halide in which the p-carbon is unusually acidic (indene derivative, 12), moderately strong bases (triethylamine and methoxide) lead to a significant Cl/ Cl isotope effect = 1.010 1.009, where a maximum effect of... 

If the intermediate configuration that is stabilized is the carbanion configuration [35], then the pattern observed is that illustrated in Fig. 26d. A concerted E2 process with ElcB character takes place and the transition state may be described by (102). If the carbanion configuration is strongly... 

The predictions of the CM model are exactly the same. In line with a simple Bell-Evans-Polanyi diagram (e.g. Fig. 18), stabilization of the product configuration leads to an earlier transition state, while stabilization of an intermediate configuration leads it increasingly to mix into the transition-state wave-function. For example, stabilization of the carbocationic configuration [36] results in the transition state acquiring more of that character so that an E2 process becomes more El-like (Fig. 266). 

The cyclic mechanism is probably seldom a fully concerted (E2) process, and the different timing of individual electron shifts results in a transition towards the El or ElcB mechanisms (cf. Sect. 2.1.1). The choice of the mechanism depends on the reactant structure as well as on the catalyst nature. As an indicator of the mechanism, either the degree of stereoselectivity (see refs. 68, 121, 132 and 141) or the value of the reaction parameter of a linear free energy relationship, e.g. p or p constants of the Hammett and Taft equations (cf. ref. 55), may be used. 

The removal of a molecule of a hydrogen halide from an alkyl halide to yield an alkene is effected under strongly basic conditions, e.g. a concentrated alcoholic solution of sodium or potassium hydroxide or alkoxide. This overall reaction has been submitted to most rigorous mechanistic studies. Most of the factors (temperature, nature of base, structure of substrate, solvent, etc.) which control product composition have been evaluated. It thus appears that under the conditions noted above, an E2 process, in which the participating sites adopt an ann -periplanar conformation leading to an anti-elimination process, is generally favoured. 

Chloride ion is a very weak base thus, the E2 process cannot compete with the SN2 reaction, and the yield of the substitution product is nearly 100%. 

Element effects. The importance of bond-breaking in either ElcB or E2 processes, which are the ones expected to operate in the formation of acetylenes, predicts high kSl/kCi ratios for the elimination-addition. 

The erythro compound shows little or no kinetic isotope effect, but the threo compound has a moderate one, H/fcD 2-3-3-3, for both syn and anti processes. This suggests that an E2 process is involved. Eliminations from the cyclic bromides may produce trans alkenes by syn eliminations or by anti eliminations, if n 8 in(189). 

Although the interactions of charged, dipolar or polarizable groups have been investigated for various purposes, they have not often been utilized in the context of stereoselectivity. In fact, when coulombic effects were considered in the SN2 or E2 processes, their role was regarded as unimportant (Ingold, 1953 Cristol, et al., 1951). In view of the substantial electrostatic (field) effects estimated for polar substituents on the pA s of carboxylic acids (Tanford, 1958), metal-ion coordination (Basolo and Pearson, 1967), etc., it will be interesting to see what effects there may be on SS. 

Depending on the reagents and conditions involved, an elimination might be a first-order (El) or second-order (E2) process. The following examples illustrate the types of eliminations we cover in this chapter. 

The E2 Reaction. The stereochemistry of the E2 process is even less well understood. It is exemplified by the decarboxylative eliminations of the vinylogous /3-hydroxy acids 5.16 and 5.18, which are both largely, although not exclusively, syn. The corresponding E2 reaction with /3-hydroxy acids is highly anti selective, in the usual way for /3 eliminations. 

Matters become more complex still in neutral conditions because now tautomeric effects can be superimposed upon steric and electronic effects. In an S e2 process 2-methyl-4-phenylimidazole is methylated by dimethyl sulfate to give a mixture of the 4-phenyl and... 

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