1,2-Elimination reactions

The elimination of hydrogen halide from organic halides under basic conditions generates alkenes and is a fundamental reaction in organic chemistry. It is sometimes carried out with a base in aqueous media. 

In contrast, the corresponding Hofmann-type eliminations of quaternary ammonium hydroxides are frequently carried out in aqueous media, which will be covered in Chapter 11. 

The reductive elimination of vicinal dihalides has been accomplished by using many reagents, including the use of aqueous media. An interesting method is the reductive elimination of vicinal dihaMdes by an electrochemical method using vitamin B12 in a water-in-oil microemulsion (Eq. 6.8).  

In an elimination reaction, two atoms or group of atoms are lost from the reactant to form a 7t-bond. Consider the following Hofmann elimination 

The elimination reaction is not very atom-economical. The percentage atom economy is 35.30%. In fact this is least atom-economical of all the above reactions. 

Consider another elimination reaction involving the dehydrohalogenation of 2-bromo-2-methylpropane with sodium ethoxide to give 2-methylpropene. 

Dehydration reactions are important for the synthesis of commodity ethers, such as tetrahydrofuran, which was synthesized from 1,4-butanediol at low yield in NCW. It is also important to note that the reverse reaction can be performed in NCW, although at a greatly reduced yield. For example, the conversion of alkenes to alcohols in NCW has been reported to proceed to 10% equilibrium conversion.  

Decarboxylation reactions are also a common type of elimination in NCW. Both aliphatic and aromatic carboxylic acids will undergo elimination of CO2 in NCW. Since decarboxylations produce CO2, the resulting carbonic acid can have an accelerating effect on numerous acid-catalyzed processes. Carlsson et al. studied the conversion of citric and itaconic acids to methacrylic acid, suggesting decarboxylation of acotinic acid yielding methacrylic acid (Fig. 9.32). The authors reported NMR evidence that supports 

Elimination reactions involve the removal from a molecule of two atoms or groups, without their being replaced by other atoms or groups. In the great majority of such reactions the atoms or groups are lost from adjacent carbon atoms, one of them very often being a proton and the other a nucleophile, Y . or Ye, resulting in the formation of a multiple bond, a l,2-(or a/ -) elimination  

Eliminations from atoms other than carbon are also known  

2-eliminations involving carbon atoms (i.e. most), the atom from which Y is lost is usually designated as the l-(a-) carbon and that losing (usually) H as the 2-(/ -) carbon in the older a/J-terminology, the a- is commonly omitted, and the reactions are referred to as p-eliminations. Among the most familiar examples are base-induced elimination of hydrogen halide from alkyl halides—this almost certainly the most common elimination of all—particularly from bromides (1)  

Many other leaving groups are known, however, e.g. SR2, S02R, 0S02Ar, etc. 1,2-Eliminations are, of course, the major route to alkenes. 

Three different, simple mechanisms can be envisaged for 1,2-eliminations, differing from each other in the timing of H—C and C—Y bond-breaking. This could (a) be concerted, 

Elimination reactions are facile processes as far as they have been studied in the gas phase. It is, however, often difficult to distinguish them from SN2 substitution reactions since both reactions mostly lead to the same product ions, but not to the same neutral products which in most experiments are not known (Smith et al., 1980 Jones et al., 1985). In that respect the reactions of cyclic compounds, such as cyclic ethers, are good probes for the study of elimination reactions because the leaving group remains with the anion. For example, the reaction of NH2 with tetrahydrofuran leads to (M — H) ions. Deuterium labelling has shown that the proton is abstracted exclusively from the P-position (DePuy and Bierbaum, 1981b DePuy et al., 1982b). 

Interesting examples of elimination reactions have also been seen in the reactions of cyclic sulphides (Bartmess et al., 1981). 1,3-Dithiolane, for example, reacts with several bases in two ways as has been confirmed by 

Overall kinetic isotope effects associated with the reaction between B and diethyl ether 

Errors calculated from the standard deviation data in Table 3. 

Elimination reactions are the opposite of addition reactions. One starting material is converted into two products. 

The mechanism of these reactions can involve a loss of a cation or anion to form ionic reaction intermediates. 

Elimination reactions of the 20-hydroxycholanic acid derivative (108) probably illustrate the differing character of the transition state, depending upon the reagent. Thionyl chloride in pyridine gave the 17(20)-enes (109 cis -I- trans, 80% total), as expected from thermodynamic control when a bimolecular elimination has considerable carbonium ion character ( l-like) in the transition state. The 20(22)-enes (110) cis + trans) were major products when phosphoryl 

Tosylates of the epimeric pregnan-20-ols undergo elimination on heating with hexamethylphosphotriamide, giving cis- and rra s-pregn-17(20)-enes.  

Phosphoryl chloride reacts with cholesterol in pyridine to give the 3-phospho-dichloridate, which has been used as a source of other cholesteryl phosphate derivatives. Elimination of the ester group occurred only on heating in dioxan, to give cholesta-3,5-diene. 

A remarkable migration of bromine was observed in the dehydrobromination of the 6, 7a-dibromo-l,4-dien-3-one (112), obtained by addition of molecular bromine to the l,4,6-trien-3-one (111). Reaction with organic bases gave the 

Other elimination reactions reported include the formation of the l(10),5-diene from a 5,6-dibromo-19-nor-steroid, and also from a 6j -methoxyoestr-5(10)- 

Elimination reactions are the opposite of addition reactions. This type of reaction generates unsaturation of the starting material and two substituents are usually removed from the starting molecule. A typical example is a dehydration reaction where there is a loss of a water molecule from the starting reagent. Alcohols can be dehydrated to alkenes accompanied by the production of a molecule of water, as shown in Schane 5.3. 

In this example, if the alcohol is propanol then the alkene is propene. The atom economy can be obtained as the mass of a propene molecule (42g/mol) divided by the original mass of the propanol molecule (60g/mol) for an atom economy of 70%. However, in this case the undesired product is water, which is innocuous, so except for the effort required to recover the alkene product, the atom economy less than 100% is not as significant from a green standpoint. 

In organic chemistry, elimination processes are those decompositions of molecules whereby two fragments are split off and the multiplicity of the bonds between two carbon atoms or a carbon atom and a hetero atom is increased. Such a broad definition also embraces the dehydrogenation of hydrocarbons and alcohols which is dealt with in Chap. 2. Here we shall restrict our review to the olefin-forming eliminations of the type 

Homogeneous olefin-forming eliminations have been studied extensively, especially in the liquid phase and comprehensive treatments of the subject are available [64,65]. The rules governing the course of homogeneous eliminations and their mechanisms are well established and the interpretation of the results obtained with heterogeneous catalytic sys- 

1 The E2 Reaction. / -Elimination, which is usually but not always stereospecifically anti, is the frequent accompaniment to substitution, as we saw earlier [see (Section 4.5.2.5) pages 145-147], We have also already had [see (Section 2.2.3.4) page 81] some discussion about why anti arrangements are preferred in the anomeric effect, where we saw that it is not solely because it allows all the groups to be staggered and not eclipsed. 

As with the anomeric effect, this is not the whole story for elimination reactions either, because there are systems where this factor is not present, and yet there is still a preference for anti elimination. Thus the anti elimination of the vinyl chloride 5.12 giving diphenylacetylene is over 200 times faster than the syn elimination of the vinyl chloride 5.13, and this in spite of the almost certainly higher energy of the latter, which has the two large substituents, the phenyl groups, cis. 

In one sense, the stereochemistry at the carbon carrying the nucleofugal group X in the anti-periplanar process 5.14 can be seen as an inversion of configuration, since the electrons supplied by the C -M bond, where M stands for any electro-fugal group, flow into the n bond of the product 5.15 from the side opposite to the 

C—X bond. This is the simplest perception available to the organic chemist to account for why E2 reactions take place with anti-periplanar geometry. 

2 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. 

Since eliminations cover a very wide spectrum of chemical reactions, this chapter is a selective discussion of the subject. The mechanistic basis of (3-eliminations is discussed, largely with reference to dehydrohalogenation, and a variety of a-eliminations are included here. Other eliminations, such as dehalogenation, are described throughout later chapters with reference to specific syntheses. 

In contrast to chemical reactions in which elimination and nucleophilic displacement are alternatives and may occur simultaneously, microbial elimiuation is less common. This term is also used for the reactiou iu which, for example, 1,2-dihaloethaues are transformed to ethene, in contrast to dehydro-halogenation in which a haloethene is produced or reductive hydrogenolysis to a haloethaue. Degradatiou iuvolviug elimiuation is found in several degradations  

A strain of Pandoraea sp. was also able to degrade die y-isomer (Okeke et al. 2002).  

The first two steps in the biotransformation of HCH involve eliminations (dehydro- 

FIGURE 7.52 Stereochemistry of first steps in the biotransformation of y-hexachlorocyclohexane. 

Strain B90A contains two copies of linA that have important consequences. The corresponding dehydrochlorinases LinAl and Lin A2 are specific for the (+) and ( ) enantiomers of a-HCH (Suar et al. 2005), and the presence of both makes possible the degradation of racemic HCH. In strains with only a single copy of the enzyme, however, degradation of only one of the enantiomers will take place with consequent enrichment of the nondegrad-able enantiomer. 

Quite often nucleophilic reactions compete with elimination reactions. Next, we will review elimination reactions. 

There are two types of elimination reactions in general — El and E2 reactions. We will first consider an E2 reaction. 

Two important modes of decomposition of transition-metal alkyls are a- and j5-elimination, while intramolecular reductive elimination, oxidative addition (e.g. y-elimination), and homolytic M—C bond fission are other pathways available. The formation of alkylidene complexes by a-elimination has been reviewed. The mechanism of a-elimination has received some attention recently but is not well worked out. The thermal decomposition of pentabenzyltantalum has the following stoicheiometry, although the nature of the Ta product is obscure  

In this chapter, we will explore elimination reactions in the same way that we explored substitution reactions. We begin with the mechanisms for El and E2 reactions, and then we move on to the factors that help us determine in each case which mechanism predominates. There is one big difference between the last chapter and this chapter. In the last chapter, most of the information was given to you, and there was very httle to look up in other sources (your textbook, your class notes, etc.). But now you know how important mechanisms are, you know that mechanisms explain everything, you know how to analyze different factors that affect reactions, and so on. So in this chapter, YOU are going to provide the key information, by filling it in the appropriate places. 

Don t worry. It will be a very interactive process. I will teU you what to look up and where to draw the information. We will go through what you need to do step by step. Let s see where we are in the grand scheme of things. 

We are in the second part of a four-phase program to get you to the point where you can study without explicit instructions. Here are the four phases  

With substitution reactions, you were given all of the information so that you could see how to go through the process of analyzing each and every factor based on the mechanisms. 

In this chapter, you will find all of the mechanisms and all of the factors yourself, but you will be told every step of the way what you should do. 

There are a number of bimolecular nucleophilic elimination reactions like that of equation (5.188) that take place in a single, concerted step. Since the transition state for such an 2 reaction is odd, being isoconjugate with the pentadienate anion (CH2 CH—CH CH—CH2) , while the reactants and products are even, -type groups at the central carbon atoms can exert mesomeric effects in the transition state that are different from those in the reactants or products. Such eliminations are therefore anti-BEP reactions and are classed as EO.  

During such a reaction, the two central carbon atoms remain bonded throughout to two neighbors. Each therefore has a single AO to contribute to the delocalized MOs in the transition state. Since these AOs are initially sp hybrids and end by being pure p AOs (in the C=C bond in the product), they overlap with one another in n fashion. For overlap to be a maximum, the AOs must be parallel and the X—C—C—Y system in the transition state consequently coplanar. The favored geometries of the transition states are consequently those indicated in Newman projections in Fig. 5.23. 

The Effl eliminations with leaving groups other than a proton are as stereoselective as the examples cited above. Thus elimination of bromine from 2,3-dibromobutane by iodide ion is stereospecifically trans, as is shown by the exclusive formation of frans-2-butene (44) from m so-dibromide (43) and of cis-2-butene (46) from rfZ-dibromide (45). 

Cis Eff2 eliminations have been observed in rigid cyclic systems e.g., 

Here the choice is between elimination of deuterium via a strictly planar cis transition state or elimination of hydrogen, which can only achieve a trans-planar configuration at the expense of distortion of the rigid ring system. 

So far, we have looked at substitution reactions and addition reactions. We will now turn our attention to elimination reactions. The overall result of an elimination reaction is, not surprisingly, the opposite of an addition reaction. However, when we come to study the details of the mechanisms that are involved in elimination reactions, we find that they are not always closely related to the reverse of addition reactions. In contrast, elimination reactions are often more closely related mechanistically to substitution reactions than to addition reactions. In fact, elimination and substitution reactions often compete with each other in the reaction mixture. 

This type of elimination is called P-elimination, or 1,2-elimination. If there were already a double bond between the a and P atoms, then a triple bond would be formed in the elimination product. 

It is possible for both groups, A and B, to be lost from the same atom, i.e. 

In this case, the initial product is a carbene. If the groups A and B had been lost from the nitrogen species, R3C-NAB, then the initial product would have been a nitrene, R3C-N . This type of 

There is a third type of elimination, which is called y-elimination, or 1,3-elimination, in which a three-membered ring is formed. Write down the general equation for this reaction. 

Mechanisms of nucleophilic substitution What factors favour elimination over (the reverse of the reactions in this 

Substitution reactions of t-butyl halides, you will recall from Chapter 15, invariably follow the S l mechanism. In other words, the rate-determining step of their substitution reactions is unimolecular—it involves only the alkyl halide. This means that, no matter what the nucleophile is, the reaction goes at the same rate. You can t speed this S l reaction up, for example, by using hydroxide instead of water, or even by increasing the concentration of hydroxide. You d be wasting your time, we said (see p. 332). 

You d also be wasting your alkyl halide. This is what actually happens if you try the substitution reaction with a concentrated solution of sodium hydroxide. 

The reaction stops being a substitution and an alkene is formed instead. Overaii, HBr has been lost from the alkyl halide, and the reaction is called an elimination. 

In this chapter we will talk about the mechanisms of elimination reactions—as in the case of substitutions, there is more than one mechanism for eliminations. We wiii compare eliminations with substitutions—either reaction can happen from almost identical starting materials, and you will learn how to predict which is the more likely. Much of the mechanistic discussion relates very closely to Chapter 15, and we suggest that you make sure you understand all of the points in that chapter before tackling this one. This chapter will also tell you about uses for elimination reactions. Apart from a brief look at the Wittig reaction in Chapter 11, this is the first time you have met a way of making simple alkenes. 

A detailed study of the transformations of methylpyrazolylketones into acetylenes under the action of PCI5 and then a base indicates the sensitivity of these reactions to experimental conditions, the structure of the starting ketones, and the nature of the base (69TZV927 69KGS1055 76TZV2288). 

Kotlyarevsky et al. (69TZV927) showed that ketones that are not substituted on the nitrogen of the ring lead to certain complications. Thus, under normal conditions (60CB593), 4-acetyl-3,5-dimethylpyrazole (6) gave a product containing significant quantities of the respective acetylene derivative 11 and an unexpected chloroacetylene 10. 

After having determined the nature of the side reaction it became clear that in order to obtain the desired ethynylpyrazole 11 the reaction between the ketone and PCI5 would have to be performed at low temperature. Indeed, the reaction was carried out in CH2CI2 at room temperature and a mixture of chlorides 7 and 8 was obtained. Dehydrochlorination of this mixture gave 66% of 3,5-dimethyl-4-ethynylpyrazole (11). Thus, by varying the conditions it is possible to carry out the reaction of the ketone with phosphorus pentachloride selectively in any of the above-mentioned directions. 

The formation of the dichlorides is aided by increased temperature (60-80°C) and by an excess of PCI5 (2-2.3 moles/mole of 4-acetylpyrazole). With a larger excess of PCI5, further chlorination of the compounds occurs. With 3 moles of phosphorus pentachloride at 80°C in benzene, ketones 12a-d gave pyrazolyl-trichloroethylenes 16a-d in 75% yield. Then dichlorides 17a-d were converted quantitatively into pyrazolyltrichloroethylenes 16a-d in 1 h under the same conditions. 

Chlorination at the position of the side chain is probably the result of phosphorylation of the intermediate vinyl chlorides followed by degradation of the phosphorus-containing products (72ZOB802). 

In an elimination reaction, a substrate loses two substituents, with a resulting increase in its number of units of imsaturation. The familiar El and E2 reactions of alkyl halides provide some of the fundamental conceptual models for vmderstanding and categorizing the reactions of organic compounds. As with substitution and addition reactions, however, simple mechanistic labels serve only as beginning points for the discussion of a wide range of elimination pathways. 

The most familiar elimination reactions are 1,2-eliminations, which are commonly known as )8-eliminations and which are termed 1/2-eliminations 

As with addition reactions, an important stereochemical distinction in elimination reactions is that of syn and anti pathways. These pathways were sometimes referred to in older terminology as trans or cis eliminations. As was noted in Chapter 9, current preference uses the terms syn and anti for mechanisms and reserves the terms cis and trans for structures. When applied to an elimination reaction, the term anti means that one group detaches from the top of the molecule (as defined by the developing bond) while the other group 

An earlier series of investigations was reported by Hughes, E. D. MacNulty, B. J. /. Chem. Soc. 1937, 1283 and earlier papers in that volume. 

Perspectives on Structure and Mechanism in Organic Chemistry, Second Edition By Felix A. Carroll Copyright 2010 John Wiley Sons, Inc. 

Kuhlmann et al. [103] reported that the treatment of a-ethyl-4-methoxy- and rf,/-4-chloro-a-propylbenzyl alcohol in pure superheated water at 277 °C resulted in elimination, wherein neither cleavage of the para substituents nor 

Cis and trans isomers of 2-methylcyclohexanol were used by Kuhlmann et al. [103] to probe whether the eliminations occurred via an Ei or E2 mechanism. That is, higher reactivity of the cis isomer could indicate the bimolecular E2 pathway because only in this isomer could the leaving group assume the required antiperiplanar conformation. Equal conversion rates would be expected for Ei reactions. Cis- and /rans-2-methylcyclohexanol were eliminated to 1-methylcyclohexanol in low yield but high selectivity (100%) in pure superheated water at 300 °C [103]. However, the treatment of the trans isomer at 270 °C yielded a mixture of methylcyclohexenes at a conversion of about 70%. Similar results were obtained for c -2-raethylcyclohexanol however, 1-methycyclohexene was more predominant than double-bond migration products. These results are still not sufficient to elucidate the mechanism or the function of water in the dehydration. Dehydration of neopentyl alcohol or pentaerythritol, concomitant with the carbon-bond migration, did not occur within 60 min at 250-300 °C. None of the alcohols examined were dehydrated to ethers. 

467 and this in spite of the almost certainly higher energy of the latter, which has the two large substituents, the phenyl groups, cis. 

The tau bond model appears to provide a quick and easy explanation. An anti interaction between each of the breaking bonds and the lower tau bond leads to a syn selective reaction for each diastereoisomer. 

The tau bond model is an intriguing, but evidently defective approach to understanding the stereochemistry of elimination reactions. The problem therefore remains—there is no simple and satisfying way to explain the stereochemistry beyond the simple /3-elimination. We shall return to the problem later, when we come to discuss how cr bonds adjacent to a re bond influence the stereochemistry of attack on the n bond, but first we must discuss the angle of attack on a re bond, and the stereochemistry of their addition and substitution reactions. 

While there is a paucity of information on neighboring sulfur involvement in elimination reactions, the results of McCabe and Livingston suggest participation in the solvolytic elimination of hydrogen chloride from the chloroalkene (91) and in the pyrolytic elimination of adipic acid from the adipate ester (92). 

On the basis of an orthojpara rate ratio of 1.1 x 10 anchimeric assistance to elimination is also proposed in the case of the oxime ester 

The reversibility of sulfenyl chloride addition allows exchange with another alkene, leading to elimination from the initial adduct. The rates of the exchange reactions vary considerably, and when an excess of an olefin that undergoes slow elimination is present with an adduct that eliminates rapidly near-quantitative exchange may occur. An appropriate exchange pair was found to be 2-chlorocyclooctyl 4-chlorophenyl sulfide (elimination half-life = 1.3 hr) and cyclopentene (elimination half-life = 400 hr) [Eq. (38)]. 

Whenever a substitution reaction is carried out, one of the side reactions which may be expected is an elimination reaction. An unsaturated linkage is formed, and a simple molecule such as water, an acid, or an amine is lost. Examples include the treatment of alkyl halides with alkali, 

In many instances (notably the last of those mentioned above), elimination is the predominating reaction. It should always be kept in mind, however, that elimination and substitution processes compete with each other and usually occur simultaneously. The one which predominates depends upon environmental as well as structural factors. It is the purpose of this chapter to discuss the mechanisms of elimination, and to 

1 For excellent references from which much of this material was adapted, see Hughes and Ingnld, Trans. Faraday Soc.t 37, 657 (1941), and Dhar, Hughes, Ingold, Mandour, Maw, and Woolf, J. Chern. Soc., 1948, 2093. 

In decomposition reactions of dimethyl-metal complexes of palladium(II) and nickel (II) one finds the formation of only traces of methane [49] which may also attributed to an a-elimination process. In regard to the valence state, note that, formally, the alkylidene ligand is considered as a neutral ligand and therefore, in the tantalum-alkylidene complex in Fig. 4.29, tantalum is trivalent. The electronic structure of the alkylidene is of course reminiscent of the corresponding oxide CpTa(Cl)20, which we would definitely call pentavalent. All that matters is that there should be a sufficient number of electrons for the multiple bonds which we draw. 

The oxidation or reduction of the central metal atom in a 71-complex occurs under varying reaction conditions and generally results in the formation of a more stable complex with altered geometry. An elimination reaction 

This reaction is reversible by the addition of hydride ion to [6-18]. Similar elimination reactions are observed for the palladium complex. An example of the use of hydrogen chloride in a reversible system is given in equation (6-32). 

Because of the activating effect of the carbonyl group, aldonolactone derivatives readily undergo -elimination reactions to yield unsaturated lactones. 

In the course of investigations (175) on the structure of evemitrose, the corresponding 1,5-lactone 129, obtained upon oxidation of the sugar, yielded the a,/ -unsaturated derivative 130 when refluxed with methanolic potassium acetate. The same enonolactone 130 was obtained from L-mycar-ose (125c). 

Oxidation of evermicose (122) with bromine yielded a mixture of y- and 5-lactones, which was directly acetylated. Refluxing the acetate in benzene solution in the presence ofp-toluenesulfonic acid gave (176) a mixture of the unsaturated lactones 131 and 132. In related work, Ganguly and Saksena (177) obtained an enonolactone by oxidation of D-nogalose with Jones reagent, followed by -elimination promoted by piperidine. Similarly, L-no-galose gave the enantiomeric lactone. 

In the aldopentose series, 2,3,4-tri-O-acetyl-a-D-xylopyranose afforded the corresponding unsaturated 1,5-lactone by oxidation - elimination. Likewise, hepta-O-acetylcellobiose gave, upon oxidation (184), the product of -elimination at the reducing end. 2,3,4,6-Tetra-O-benzoyl-D-gluco- and D-mannopyranoses were not oxidized by the same reagents. 

5-tri-0-acetyl-6-0-trityl-D-galactono-1,4-lactone being the major product (196). In contrast, 5,6-0-isopropylidene-D-galactono-, L-gulono-, and 

P-Eliminations (Equation 10.1) are the most common type of elimination reaction from transition metal complexes, and p-hydrogen eliminations from metal-alkyl complexes are the most common type of p-elimination reactions. p-Hydrogen elimination from aUcoxo and amido complexes has also been observed in a few cases. p-Alkyl elimination, p-aryl elimination, p-aUcoxide elimination, and p-chloride elimination have also been observed and have been studied carefully because of their importance as side reactions in catalytic chemistry. Although P-hydrogen elimination from metal-alkyl complexes occurs almost exclusively by migratory de-insertion pathways, p-hydrogen ehmmation from alkoxides has been shown to occur by several different pathways. 

Incorporation of halogen into a molecule is important because halides are often precursors for substitution or elimination reactions. The ability to convert alcohols to halides is therefore an important functional group transformation. The transform is 

There are several types of reactions in which a halogen, a sulfonate ester, or another functional group is lost from the molecule, along with a hydrogen or sometimes another functional group to generate a carbon-carbon double bond. Both alkenes and alkynes can be formed. This section will examine methods for the formation of such molecules via elimination reactions.A recent monograph describes several different preparations of alkenes. 

As with substitution, we have two mechanisms that are relatively common and one that is much rarer. The two common mechanisms, El and E2, have strong similarities to the S l and 5 2 processes described in the previous chapter and are generally favored by similar conditions to these analogues. The third mechanism, ElcB, is rather different, with no direct analogy in substitution chemistry. We will initially exemplify all the reactions by removal of hydrogen halides, HX, in the presence of base and then explore the scope of the reactions. 

In the previous chapter, we saw that a substitution reaction can occur when a compound possesses a leaving group. In this chapter, we will explore another type of reaction, called elimination, which can also occur for compounds with leaving groups. In fact, substitution and elimination reactions frequently compete with each other, giving a mixture of products. At the end of this chapter, we will learn how to predict the products of these competing reactions. For now, let s consider the different outcomes for substitution and elimination reactions  

Until now, discussions have focused only on how carbanions and carbocations behave under conditions favorable for nucleophilic substitutions. However, these species may undergo other types of reactions in which unsaturation is introduced into the molecule. Such reactions are called elimination reactions and should be considered whenever charged species are of importance to the mechanistic progression of a molecular transformation. In previous chapters, SN1 and SN2 reactions were discussed. In this chapter, the corresponding El and E2 elimination mechanisms are presented. 

Alkene synthesis is the most important and most widely used reaction in organic chemistry. Many review articles and research papers describe methods for the positioning and stereospecific introduction of carbon-carbon double bonds . The three most important methods for the synthesis of alkenes described in this chapter are (1) elimination reactions, (2) aUcenation of carbonyl compounds and (3) reduction of alkynes. 

In an elimination reaction the carbon skeleton is pre-assembled. There can be two problems, namely the positioning of the double bond and that of double bond geometry. 

When 2-bromopropane (4.1) is allowed to react with the methoxide ion in methanol, only 40% of the starting material is converted into methyl isopropyl ether (4.2) (substitution) and the rest (60%) is transformed into propene (4.3) (elimination). Substitution and elimination are often competitive processes. The reaction that produces the alkene involves the loss of an HBr molecule to form a carbon-carbon double bond. 

The E2 dehydrohalogenation of alkyl halides is periplanar and occurs most favourably with the proton and halide in an anfi-configuration. The formation of the E- or Z-alkene 

And the most stable alkene (most substituted) is the usual product (Saytzeff rule). 

The work of H. C. Brown has made hydroboration an enormously useful synthetic reaction. Oxidation of the adduct with alkaline hydrogen peroxide removes the boron smoothly without rearrangement and replaces it by a hydroxy group. The oxidation proceeds entirely with retention of configuration. For example, the product of Reaction 7.19 is converted by oxidation to trans-2-methylcyclopentanol in high yields (Equation 7.20). 

Thus hydroboration of a double bond followed by peroxide oxidation is a convenient procedure for converting the olefin into the alcohol corresponding to anti-Markownikoff addition of water. 

The opposite of an addition to a double bond is a 1,2-elimination reaction. In solution, where the reaction is promoted by solvent or by base, the most common eliminations (and those to which we shall limit our discussion) are those that involve loss of HX, although loss of X2 from 1,2-dihalides and similar reactions are also well known. The mechanisms of eliminations of HX are of three main types (1) The Ex (elimination, first-order), shown in Equation 7.22, which is the reverse of the AdE2 reaction and which has the same first, and rate-determining, 

We shall discuss each of these mechanisms and also, very briefly, 1,2-eliminations that require assistance of neither solvent nor base. 

Whether a ft proton is lost from the same or the opposite side of the molecule as the leaving group, that is, whether syn or anti elimination obtains in a Ex mechanism depends on the reaction conditions. If a solvated, planar carbocation 

The abbreviation E2 conveys the information elim-ination-bimolecular . The reaction is a concerted process in which a nucleophile removes an electrophile at the same time as a leaving group departs. It is bimolecular, since kinetic data indicate that two species are involved in the rate-determining step  

The electrophile removed is usually hydrogen, so we can consider that the nucleophile is acting as a base. We have seen above the close relationship between basicity and nucleophilicity (see Section 6.1.2), so the E2 mechanism provides an example of how the alternative property of nucleophiles may come into play and lead to different products. To achieve an Sn2 reaction, the nucleophile must approach to the rear of the leaving group and then displace it (see Section 6.1). If a rear-side approach is hindered by adjacent groups, or perhaps because the nucleophile is rather large, it becomes energetically easier for the nucleophile to act as a base and remove a proton from the substrate. 

The requirement for the proton electrophile and the leaving group involved in the elimination to be anti to each other is demonstrated by the nature of the product obtained from a suitable substrate, e.g. 

It is particularly evident that the anti stereochemical relationship is obligatory by observing elimination reactions in suitable cyclohexane derivatives. The only way to achieve a planar arrangement of 

Treatment of neomenthyl chloride with base rapidly produces two different alkenes, i.e. 2-menthene and 3-menthene. If one considers the three-dimensional shape of neomenthyl chloride, it can be seen that, in the preferred conformer with the two alkyl groups equatorial (see Section 3.3.2), the chlorine is an axial substituent. This means there are two different hydrogen atoms adjacent that are also axial and anfi-periplanar to the chlorine. As a conseqnence, two different E2 eliminations can occnr hence the two observed prodncts. That the two prodncts are not formed in eqnal amonnts will be considered in the next section. 

Exercise 8-22 Classify the following solvents according to effectiveness for solvation of (i) cations and (ii) anions  

Exercise 8-23 Would you expect the SN2 reaction of sodium cyarnde with methyl bromide to be faster, slower, or about the same with (CH3)2S=0 or ethanol as solvent Explain. 

Generally, an alkyl derivative, under appropriate conditions, will eliminate HX, where X is commonly a halide, ester, or -onium function, provided that there is a hydrogen located on the carbon adjacent to that bearing the X function ,  

An important feature of many elimination reactions is that they occur with the same combinations of reagents that cause nucleophilic substitution. In fact, elimination and substitution often are competitive reactions. Therefore it should be no surprise that substitution and elimination have closely related mechanisms. 

Brandsma, Preparative Acetylenic Chemistry, Elsevier, Amsterdam (1971), p 189 J Chem Res (S) 106 (1978) 

R = 1°, 2°, 3° alkyl allylic aryl vinylic E+ = H20, n-BuBr, CH3CHO, Me3SiCl 

E+ =RCHO, R2CO (CeClj), RCOC1 [Zna2, cat Pd(PPh3) ], RCONMeOMe JOC 60 3550 (1995) 

ArCCH—CCH3 Tm sIS ArCC=CCH3 3. HOAc, NaOAc 

In the next chapter (addition reactions), you will be asked to draw the mechanisms and record the important factors by yourself, without too much help. 

This reaction is a key early step in the production of the transparent plastic known as Plexiglas or Lucite. 

An elimtnatian reaction involves a decrease in the number of atoms or groups attached to carbon. The degree of unsaturation increases. 

An elimination reaction, dehydrohalogenation, can occur for chloro-, hromo-, and iodoalkanes. In such a reaction, the halogen, X, from one C atom and a hydrogen from an adjacent C atom are eliminated. A double bond between two carbon atoms is formed the molecule becomes Tnore unsaturated. The net reaction is the transformation of an alkyl halide (or haloalkane) into an alkene. Dehydrohalogenation reactions usually require a strong base such as sodium hydroxide, NaOH. 

A related reaction is dehydration, in which an alcohol is converted into an alkene and water by the elimination of H— and —OH from adjacent carbon atoms. The 

Concentrated snHnric acid is an excellent dehydrating agent. Here it removes water from sncrose, a sngar with the formnia C12H22O11. Dehydration of sncrose prodnces large amounts of carhon and heat. 

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Nucleophilic substitution of benzene itself is not possible but the halogeno derivatives undergo nucleophilic displacement or elimination reactions (see arynes). Substituents located in the 1,2 positions are called ortho- 1,3 meta- and 1,4 para-. 

N,N,N, N -tetramethyl-l,8,-naph-thalenediamiDe M.P. 51 C. A remarkably strong mono-acidic base (pKg 12-3) which is almost completely non-nucleophilic and valuable for promoting organic elimination reactions (e.g. of alkyl halides to alkenes) without substitution. 

Figure 3-3. Representative, simple examples of a substitution, an addition, and an elimination reaction showing the number, n, of reaction partners, and the change in n, An, during the reaction.

Figure 3-4. a) The reaction site of an elimination reaction. The bonds to be broken are crossed through, and the bonds to be made are drawn with heavy lines, b) to d) The three mechanisms to achieve this reaction,... 

The stereochemistry of reactions can also be treated by permutation group theory for reactions that involve the transformation of an sp carbon atom center into an sp carbon atom center, as in additions to C=C bonds, in elimination reactions, or in eIcctrocycHc reactions such as the one shown in Figure 3-21. Details have been published 3l]. 

Note that for 4.42, in which no intramolecular base catalysis is possible, the elimination side reaction is not observed. This result supports the mechanism suggested in Scheme 4.13. Moreover, at pH 2, where both amine groups of 4.44 are protonated, UV-vis measurements indicate that the elimination reaction is significantly retarded as compared to neutral conditions, where protonation is less extensive. Interestingy, addition of copper(II)nitrate also suppresses the elimination reaction to a significant extent. Unfortunately, elimination is still faster than the Diels-Alder reaction on the internal double bond of 4.44. 

Clearly, the use of diamine 4.43 as a coordinating auxiliary is not successful. However, we anticipated that, if the basicity of the tertiary amine group of the diamine could be reduced, the elimination reaction will be less efficient. We envisaged that replacement of the tertiary amine group in 4.43 by a pyridine ring might well solve the problem. 

Most importantly, analysis using UV-spectroscopy also demonstrated that, as anticipated, the elimination reaction of 4.51 is less efficient than that of 4.44. Ag in, addition of copper(II)nitrate significantly suppresses this reaction. 

Fortunately, in the presence of excess copper(II)nitrate, the elimination reaction is an order of magnitude slower than the desired Diels-Alder reaction with cyclopentadiene, so that upon addition of an excess of cyclopentadiene and copper(II)nitrate, 4.51 is converted smoothly into copper complex 4.53. Removal of the copper ions by treatment with an aqueous EDTA solution afforded in 71% yield crude Diels-Alder adduct 4.54. Catalysis of the Diels-Alder reaction by nickel(II)nitrate is also... 

Fortunately, under moderately acidic conditions, in the presence of acetone and paraformaldehyde, 4.54 undergoes an elimination reaction similar to that described in Scheme 4.13, producing oc,(3-... 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

J Olefin Syntheses by Dehydrogenation and Other Elimination Reactions 137... 

Table 3 summarizes some selective elimination reactions of synthetic interest. Table 3. Selective elimination reactions.

TosOH 4-methylbenzenesulfonic acid = p toluenesiilfonic acid, tosic acid X, Y leaving groups. e.g., halogen, RSOj, in substitution and elimination reactions... 

As a typical example, the catalytic reaction of iodobenzene with methyl acrylate to afford methyl cinnamate (18) is explained by the sequences illustrated for the oxidative addition, insertion, and /3-elimination reactions. 

Aryl or alkenyl halides attack the central carbon of the allene system in the 2,3-butadien-l-ol 120 to form the 7r-allyl intermediate 121, which undergoes elimination reaction to afford the o,/3-unsaturated ketone 122 or aldehyde. The reaction proceeds smoothly in DMSO using dppe as a ligandflOl]. 

In steroid systems, the homoannular diene in ring A and the heteroannular diene in AB rings are generated. The allylic 3a-carbonate 514 affords the homoannular conjugated diene 515 as a main product and a small amount of the heteroannular diene 516. On the other hand, the heteroannular conjugated diene 516 is obtained exclusively from 33-carbonates 517. The elimination reaction proceeds smoothly at room temperature. 

BU3P. A rapid redox reaction takes place to yield the active Pd(0) species and tributylphosphine oxide. The Pd(0) thus generated is a phosphine-free cata-lyst[341]. Severe reaction conditions are necessary, or no reaction takes place, when Pd2(dba)3 is used in the elimination reaction of cyclic allylic compounds with an excess of -Bu3P[342]. 

The optically active 1,4-cyclohexenediol monoacetate 525, prepared by hydrolysis of the me.so-diacetate with lipase, was converted into the optically pure cyclohexenone 526 by an elimination reaction in the presence of ammonium formate. Optically active carvone (527) was prepared from 526[343],... 

Another protecting group of amines is 1-isopropylallyloxycarbonyl, which can be deprotected by decarboxylation and a /3-elimination reaction of the (tt-l-isopropylallyl)palladium intermediate under neutral conditions, generating CO2 and 4-methyl-1,3-pentadiene. The method can be applied to the amino acid 674 and peptides without racemization[437]. 

The allyl cyanoacetate 731 can be converted into an a, /3-unsaturated nitrile by the decarboxylation-elimination reaction[460], but allyl malonates cannot be converted into unsaturated esters, the protonation and allylation products being formed instead. 

The reaction of isoprene with MeOH catalyzed by Pd(acac)2 and Ph3P is not regioselective, giving a mixture of isomers[37]. However, l-methoxy-2,6-dimethyl-2,7-octadiene (35), the head-to-tail dimer, was obtained in 80% yield, accompanied by the tail-to-tail dimer (15%) using 7r-allylpalladium chloride and BU3P. On heating, 35 was converted into 2.6-dimethyl-1,3,7-octatriene (36) by an elimination reaction[38]. 

CHAPTER FIVE Structure and Preparation of Alkenes Elimination Reactions... 

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