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Richard F. Daley and Sally J.

Daley
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Organic Chemistry
Chapter 13

Elimination Reactions
13.1 The Elimination Mechanisms 658 13.2 Stereochemistry of Eliminations 660 13.3 Direction of Elimination 663 13.4 E1 vs. E2 670 13.5 Elimination vs. Substitution 671 13.6 Summary of Elimination and Substitution 13.7 E & Z Nomenclature 677 13.8 Elimination of Organohalogens 678 13.9 Dehydration of Alcohols 682 Synthesis of Cyclohexene 685 13.10 Pinacol Rearrangement 686 13.11 Hofmann Elimination 691 13.12 Oxidation of Alcohols 694 Synthesis of Citronellal 697 Key Ideas from Chapter 13 698

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Copyright 1996-2005 by Richard F. Daley & Sally J. Daley All Rights Reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the copyright holder.

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Chapter 13

Elimination Reactions
Chapter Outline
13.1 13.2 13.3 13.4 13.5 13.6 13.7 13.8 13.9 13.10 13.11 13.12 The Elimination Mechanisms
An overview of the two types of elimination mechanisms

Stereochemistry of Eliminations
A look at the stereochemical requirements of an elimination reaction

Direction of Elimination
Regioselectivity of the elimination mechanisms

Comparing E1 and E2 With SN1 and SN2 Reactions Comparing the E1 with the SN1 reaction and the E2 with the SN2 mechanism Elimination Versus Substitution
Factors that influence whether an elimination or substitution reaction will occur

Summary of Elimination and Substitution


A summary of the factors that favor the various substitution and elimination mechanisms

E and Z Nomenclature
Naming alkenes using E and Z nomenclature

Elimination of Organohalogens
Elimination reactions involving organohalogen substrates

Dehydration of Alcohols
Elimination reactions involving alcohol substrates

Pinacol Rearrangement
The elimination/rearrangement reaction involving a 1,2-diol

Hofmann Elimination
An elimination reaction involving a nitrogen substrate

Oxidation of Alcohols
Elimination reactions involving primary and secondary alcohols

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Objectives
Be able to write E1 and E2 mechanisms Recognize the stereochemistry required for the substrate to react via an E1 or E2 mechanism Know the regiochemistry of the product of an elimination reaction Know how to predict whether a substitution or elimination reaction will occur with a particular substrate and set of reaction conditions Apply the E and Z descriptors to naming alkenes Predict the products of elimination reactions involving organohalides, alcohols, and vicinal diols Recognize the regiochemistry of the Hofmann elimination reaction Know the various pyrolytic eliminations Know the elimination reaction involving alcohols that form carbonyl compounds

Nothing in his life becomes him like the leaving it. Shakespeare

hapter 12 covered the continuum of SN1 and SN2 aliphatic nucleophilic substitution reactions. Recall, however, that a competing elimination reaction takes place under some conditions instead of the intended substitution reaction. In a -elimination reaction, the substrate loses two atoms or two groups of atoms to form a bond. This new double bond forms after, or concurrent with, the loss of the leaving groups. Usually these atoms, or groups of atoms, leave from adjacent atoms. This chapter covers two types of 1,2-, or -, elimination reactions and how they fit into the continuum with each other and with nucleophilic substitution reactions. Organic chemists use various methods to selectively control which of the possible pathways that a particular elimination reaction follows. One other major elimination

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reaction is the 1,1-, or -, elimination reaction. Chapter 14 briefly discusses the -elimination.

13.1 The Elimination Mechanisms


1,2-Elimination reactions follow two mechanistic pathways. Both pathways involve the loss of the elements E and L from adjacent atoms in the substrate to form a bond. E is some electrophile, often a proton, and L is the leaving group. L has the same characteristics of the leaving groups studied in Chapter 12.

C E

C L A 1,2-elimination

For a discussion of nucleophiles see Section 12.6, page 000. See Figure 12.2, page 000 for the energy profile of the SN1 reaction mechanism.

The two mechanistic pathways that 1,2-elimination reactions take are designated as E1 and E2. The E stands for the elimination pathway, and the number describes the kinetics of the reaction either unimolecular or bimolecular. E1 and E2 reactions relate closely to SN1 and SN2 reactions, so both a substitution reaction and an elimination reaction frequently take place competitively on a particular substrate. The E1 mechanism proceeds best on a tertiary substrate or some other substrate that forms a stabilized carbocation intermediate. The energy profile for the E1 mechanism is very similar to that for the SN1 mechanism. The first step of an E1 mechanism is identical to the ionization operation in the first step of an SN1 mechanism. The leaving group departs, and the substrate forms a carbocation. The second step, the 1,3-electron pair abstraction operation, is the fast step. In it, the carbocation loses a proton and forms the double bond. Figure 13.1 summarizes the two steps of the E1 mechanism.
L C H C H C C
+
L

C H

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Figure 13.1. The E1 reaction mechanism. The first step is an ionization operation and the second is a 1,3-electron pair abstraction operation.

Hyperconjugation stabilizes the carbocation in the second step of the E1 mechanism and actually makes the electrophile depart more readily. Because the overlap between the empty p orbital on the carbocation and the bond on an adjacent carbon lowers the electron density of the bond, the bond breaks more readily. Figure 13.2 illustrates this process.

Overlap

H C C

Figure 13.2. The orbital interactions of the second step in the E1 mechanism show how the hyperconjugation of the carbocation leads to loss of a hydrogen electrophile.

The transition state of an E2 mechanism involves both the leaving group and the base, so reactions that follow the E2 mechanism are concerted. The base removes the electrophile, often a proton, at the same time that the leaving group departs. Also, while the reaction is in the transition state, the overlap of the orbitals for the double bond begins forming. The reaction rate of an E2 mechanism depends on the concentrations of both the substrate and the base. Figure 13.3 summarizes the two steps in the E2 mechanism.
-

L C H
B

C
-

C B H

Transition State

+ L

+ BH

Figure 13.3. The E2 mechanism is a 1,5-electron pair displacement operation.

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The E2 reaction has a very similar energy profile to the SN2 reaction. Because the E2 reaction is concerted, it usually requires less activation energy to proceed than does an E1 reaction. That is, simultaneous bond breaking and bond formation requires less activation energy than does sequential bond breaking and bond formation.

13.2 Stereochemistry of Eliminations


This section describes the stereochemistry of the E1 and E2 reaction mechanisms and compares them with the stereochemistry of the SN1 and SN2 reaction mechanisms, which are covered in Chapter 12. The E1 reaction mechanism is a two-step process that, as with the SN1 mechanism, usually loses all the stereochemical information of the substrate as the reaction proceeds. The E2 mechanism, similar to the SN2 mechanism, is a concerted mechanism. A concerted reaction usually requires that the substrate have a specific conformation. The conformation must allow the orbitals of the bonds being broken to overlap the bonds being formed. Only when the orbitals overlap do the electrons flow smoothly from the breaking bonds to the forming bonds. Without this smooth flow of electrons, a concerted reaction does not take place. An SN2 reaction requires a geometric arrangement that leaves the rear of the electrophilic carbon open for reaction from the side opposite from the leaving group. An elimination reaction following the E2 mechanism requires that the leaving group and the electrophilic group be coplanar. Coplanar groups exist in two conformations called anticoplanar and syn-coplanar. In the anti-coplanar conformation, the torsion angle between the electrophile and leaving group is 180o. In the syn-coplanar conformation, the torsion angle between the electrophile and the leaving group is 0o.
L H L

When the leaving group and the electrophilic group are in the same plane, they are coplanar. When the leaving group and the electrophilic group are in a plane on opposite sides of the molecule in a staggered conformation, they are anti-coplanar. When the leaving group and the electrophilic group are in the same plane on the same side of the molecule in an eclipsed conformation, they are syn-coplanar.

L H
H Anti

Syn Coplanar conformations

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Review conformational stabilities in Section 3.4, page 000.

Of these two conformations, the anti-coplanar conformation is generally more stable. Thus, most E2 eliminations occur when the substrate is in the anti-coplanar conformation. In some cases, where the anti-coplanar conformation is not possible, the syn-coplanar elimination does occur, but at a much slower rate. The anti-coplanar conformation puts the electron-rich base as far away from the electron-rich leaving group as is possible, as shown in Figure 13.4a. In comparison, the syn-coplanar conformation puts the leaving group and the electrophilic group in the higher energy eclipsed conformation shown in Figure 13.4b. Because the base comes close to the leaving group in the syn-coplanar conformation, if the leaving group is large (which many are) then the leaving group stops the base and repels it. Thus, the syn-coplanar conformation is less stable than the anti-coplanar conformation.

C
L

Anti-coplanar E2 elimination

(a)
Repulsion B L

Syn-coplanar E2 elimination

(b)
Figure 13.4. Orbital picture of E2 elimination reactions in the (a) anti- and (b) syncoplanar conformations.

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Section 3.10, Page 000, discusses the stability of various substituents on a cyclohexane ring.

The difference in elimination pathways between cis- and trans4-tert-butylcyclohexyl tosylate illustrates the importance of molecular conformation. Because of its size, the tert-butyl group effectively locks the cyclohexane ring with the tert-butyl group in the equatorial position. In the cis isomer, the smaller tosylate group is in the axial position; and in the trans isomer, it is in the equatorial position.
OTs (CH3)3C OTs

(CH3)3C cis-4-tert-Butylcyclohexyl tosylate

trans-4-tert-Butylcyclohexyl tosylate

Both compounds react with ethoxide ion in ethanol to eliminate the tosyl group and a hydrogen to form 4-tert-butylcyclohexene. However, the reaction of the cis isomer follows E2 kinetics, whereas the reaction of the trans isomer follows E1 kinetics. The cis isomer has the tosyl group and the hydrogen in an anti-coplanar conformation; thus, allowing the base to easily remove the hydrogen.

OTs

(CH3)3C H

(CH3)3C OCH2CH3 4-tert-Butylcyclohexene

Because of the size of the tert-butyl group, the trans isomer does not easily get into either the anti- or syn-coplanar conformation. Thus, the rate of reaction is quite slow.
C(CH3)3 (CH3)3C H H OTs H OCH2CH3

OTs

(CH3)3C

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Exercise 13.1 What is the approximate dihedral angle between the hydrogens and the tosylate group in trans-4-tert-butylcyclohexyl tosylate? Draw a Newman projection looking from carbon 1 towards carbon 2. The structure of a molecule such as 2-bromo-3deuterobicyclo[2.2.1]heptane is so rigid that it exists only in the syncoplanar conformation. Chemists labeled this compound with a deuterium atom trans and a hydrogen atom cis to a bromine atom and followed the course of the E2 reaction.
Br H

Syn-coplanar

H D 2-Bromo-3-deuterobicyclo[2.2.1]heptane

They knew that if the elimination product contained the deuterium atom, then syn-coplanar elimination took place. If the product contained the hydrogen, then another process took place because the molecule was so rigid that the deuterium atom could not move back and forth between the syn- and anti-coplanar conformations. The experimental results showed that the product contained deuterium, thus, the reaction followed a syn-coplanar E2 mechanism.
Br H H D

CH3O CH3OH D

2-Deuterobicyclo[2.2.1]-2-hexene (87%)

Exercise 13.2 The threo isomer of 1-bromo-1,2-diphenylpropane undergoes elimination at a faster rate than does the erythro isomer. Explain the rate difference.

13.3 The Direction of Elimination


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In an elimination reaction, the substrate loses the leaving group and, in most cases, a hydrogen to the leaving group. Frequently, the leaving group has more than one type of hydrogen and, depending on a number of factors, any one of these hydrogens can leave with the leaving group. For example, in the elimination reaction of HBr from 2-bromobutane a hydrogen from either carbon 1 or carbon 3 leaves with the bromine. Experimental results indicate that the reaction mixture contains 1-butene (19%), cis-2-butene (22%), and trans-2-butene (59%).
Br CH3CH2CHCH3 2-Bromobutane CH3CH2O CH3CH2OH H CH3CH2CH 1-Butene 19% CH2 + C C H

CH3 H3C cis-2-Butene 22% H + H3C C C H CH3

trans-2-Butene 59%

The regio prefix means a preference for the location of the functional group in the product. Specific means only one product. Selective means one major product with a minor product(s). A Saytzeff orientation produces the more substituted alkene. The Hofmann orientation produces the less substituted alkene.

Elimination reactions may be either regiospecific or regioselective. Regiospecific elimination reactions produce only one isomer of an alkene. Regioselective elimination reactions, on the other hand, produce several different isomers, but give one isomer in greater quantity than the others. Whether a reaction is regiospecific or regioselective depends on whether the reaction prefers to eliminate only one particular hydrogen or a mixture of hydrogens. The elimination of 2-bromobutane mentioned previously eliminates a mixture of hydrogens, so it is regioselective. When an elimination reaction produces the more highly substituted alkene, for example, 2-butene from 2-bromobutene, the reaction is said to follow the Saytzeff orientation. If the elimination reaction forms the less substituted alkene, for example, 1-butene from 2-bromobutene, the reaction is said to follow the Hofmann orientation. A number of factors including the substrate, the leaving group, and the reaction conditions determine whether a reaction follows the Saytzeff or the Hofmann orientation. Because the more stable isomer of a particular alkene is the most substituted isomer, most elimination reactions follow the Saytzeff orientation. In comparison to a hydrogen, alkyl groups help to stabilize a double bond. Alkyl groups are slightly electron donating, whereas hydrogens are slightly electron withdrawing.

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One way to measure stabilization is to measure the amount of energy given off when hydrogen adds to a double bond to form an alkane.
H2 Pt

C H

C H

This method is also convenient for comparing the energy content of various alkenes. For example, the energy released by hydrogenation of 1-butene is 30.3 kcal/mole. For cis-2-butene, it is 28.6 kcal/mole; and for trans-2-butene, it is 27.6 kcal/mole. All three compounds hydrogenate to produce butane.

30.3 kcal/mole 28.6 kcal/mole H2/Pt

27.6 kcal/mole

Figure 13.5 shows the relationship between the Gibbs free energy of the three butene isomers.

Goterminal Gotrans Gocis

Figure 13.5. The reaction energy diagram for the free energies of hydrogenation of the three butene isomers.

The data in Table 13.1 show that the energy needed to hydrogenate a double bond decreases and the stability of a double bond increases, as the number of alkyl substituents bonded to a

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double bond increases. For example, the hydrogenation of 2,3dimethyl-2-butene requires 6.1 kcal/mole less energy than the hydrogenation of ethene (26.6 (32.7) = 6.1). So 2,3-dimethyl-2butene is 6.1 kcal/mole more stable than ethene. Name Structure Gibbs Free Energy of Hydrogenation (kcal/mole) 32.7
CH2 H C CH3 C CH3 CH3 C CH3 C H CH3 C CH3 C CH3 CH3 C CH3 C CH3

Ethene 1-Butene cis-2-Butene

CH2

CH2

CH3CH2CH H

30.3 28.6

trans-2-Butene

27.6

2-Methyl-2-butene

26.9

2,3-Dimethyl-2butene

CH3

26.6

Table 13.1. Gibbs free energies of hydrogenation for various alkenes.

When the pathway of an elimination reaction proceeds along the E1 mechanism, the direction of elimination usually follows the Saytzeff orientation. It does so because the rapid second step of the E1 mechanism loses the electrophile with the lowest bond energy. An E2 reaction mechanism shows less discrimination between the Saytzeff and Hofmann products. With an E2 reaction, the energy difference between the various double bond positions is often small enough that there is not a strong preference for the Saytzeff product. An example is the loss of HBr from 2-bromobutane with ethoxide ion. The product mixture contains 19% 1-butene and 81% of a mixture of cis- and trans2-butene. Although the difference between 19% and 81% may seem large, for a chemist it may not be large enough to make the reaction synthetically useful. Additionally, the difficulty in separating the cis and trans isomers may make other synthetic methods more attractive.

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Although the bond energy of a double bond is not a significant influence in determining whether the course of the E2 process follows the Saytzeff orientation or the Hofmann orientation, steric factors are significant. If the leaving group is large, then the Hofmann product predominates. For example, a quaternary ammonium salt has a large trialkylamine as the leaving group, so an E2 reaction produces the less substituted alkene in the greater amount. The difference here between 95% and 5% is synthetically significant.
N(CH3)3 OH CH3CH2CHCH3 N,N,N-Trimethyl-2-butylammonium hydroxide CH3CH2CH 1-Butene 95% CH2
+

CH3CH

CHCH3

2-Butene 5%

Hofmann eliminations are discussed in more detail in Section 13.11, page 000.

The quaternary ammonium salt in this reaction is large, so the base causes crowding within the substrate as it approaches. This crowding increases the energy of the transition state and reduces the rate of reaction compared to a smaller leaving group. Thus, the base more easily abstracts a hydrogen from the less substituted carbon to produce a less substituted alkene. Further evidence for the steric sensitivity of the E2 elimination is the observation that, in reactions using the same substrate, the amount of Hofmann elimination product increases with increasing base size.
Br CH3CH2CHCH3 CH3CH2O CH3CH2OH

CH3CH2CH 19%

CH2

CH3CH CHCH3 81%

Br CH3CH2CHCH3

(CH3)3CO (CH3)3COH

CH3CH2CH 77%

CH2

CH3CH CHCH3 23%

Solved Exercise 13.1 Draw the structure for the elimination product of each of the following reactions. a)

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Br KOH

Solution There are two possible elimination products from this reaction: 3-methyl-1butene and 2-methyl-2-butene. Br KOH

3-Methyl-1-butene

2-Methyl-2-butene

The major product is 2-methyl-2-butene because there are three alkyl substituents attached to the carboncarbon double bond. 3-Methyl-1-butene has only one substitutent. b)

CH3 KOH Br
Solution In this reaction there are two possible products: 1-methylcyclohexene and 3methylcyclohexene.

CH3 KOH Br 1-Methylcyclohexene 3-Methylcyclohexene +

Because 1-methylcyclohexene has three alkyl groups attached to the double bond and 3-methylcyclohexene has only two, you would expect 1methylcyclohexene to be the major product. However, the anti conformation of 1-bromo-2-methylcyclohexane required for the E2 elimination cannot exist.

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This hydrogen is anti to the Br. H

CH3 H Br This hydrogen cannot be anti to the Br.

Thus, the 3-methylcyclohexene is the major product formed in this reaction.

Exercise 13.3 Give the structure of the major elimination product for each of the following substrates with sodium ethoxide in ethanol. a)
CH3 Br

b)
CH3 CH3CH2CH2C CH3 CHCH3 Br

c)
Br C(CH3)3 H

d)
Br H C C H CH3

Sample solution b)

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CH3 CH3CH2CH2C CH3 CH CH2

13.4 Comparing E1 and E2 with SN1 and SN2


Much of the information covered in Chapter 12 about the SN1 and SN2 reaction mechanisms also applies to the E1 and E2 reaction mechanisms. The two pairs of reaction mechanisms are very similar and very competitive with each other. This section looks at the similarities of the substitution and the elimination mechanisms, as well as pointing out the differences between the two elimination mechanisms. Section 13.5 begins outlining the competition between elimination reactions and substitution reactions. Similar to the SN1 reaction, an E1 reaction occurs best on a tertiary substrate under reaction conditions that enable the formation of a carbocation. Both reaction types require a neutral or acidic reaction mixture because carbocations do not form under basic conditions. An E1 reaction also depends on the presence of a polarprotic solvent to promote ionization. The more polar solvents allow a secondary substrate to undergo E1 eliminations, but primary substrates usually do not. The E2 mechanism and SN2 mechanism are very similar, but there are some differences in the reactions. An SN2 reaction proceeds best with primary substrates and most poorly with tertiary substrates, whereas an E2 reaction is just the opposite. E2 reactions proceed best with tertiary substrates and most poorly with primary substrates. This preference for tertiary substrates is because they have less steric hindrance to the approach of the base to the hydrogens than to the approach of the nucleophile to the carbon bearing the leaving group in an SN2 reaction. Figure 13.6 illustrates this concept.
Protons are easy to access for E2 OH Carbon is difficult to access for SN2 CH3 CH3 C Cl

CH3

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Figure 13.6. The protons on a carbon adjacent to a tertiary leaving group are more open to reaction than the backside of the carbon bearing the leaving group.

Both the E2 mechanism and the E1 mechanism work best on tertiary substrates and more poorly on primary substrates. Generally, the difference is that the E1 reaction requires acidic reaction conditions and higher temperatures to proceed because the strongly acidic carbocation intermediate is formed. A carbocation cannot be formed in a base. Most, but not all, E2 reactions require basic reaction conditions to proceed.

13.5 Elimination versus Substitution


A problem you will face when planning a synthesis is the competition between elimination and substitution reactions. These two important reaction types are closely related mechanistically, but they lead to very different products. Except with a tertiary substrate, the substitution pathway predominates in the competition between elimination and substitution reactions because substitution reactions require fewer bond changes and have fewer conformational requirements. Therefore, they are usually more energetically favorable. By choosing reaction conditions that favor one pathway compared to the other pathway, you can control the outcome of the reaction. Three variables that affect whether a particular substrate follows the elimination or substitution pathway are: the strength and concentration of the incoming base or nucleophile, the reaction medium, and the reaction temperature. The first variable is the most important of the three because changes in the strength or concentration of the base have the greatest effect on the course of the reaction. The other two variables have a significant, though smaller, effect on the course of the reaction. The presence of a strong nucleophile usually forces a second order kinetics, either SN2 or E2. When the nucleophile is a soft base, it promotes substitution; when it is a hard base, elimination results. For example, chemists often use the hard base - OH ion to promote elimination, in preference to using the softer - SH ion. In the presence of low concentrations of base, or with weaker bases, the amount of E1 reaction increases. This increase occurs because both the E1 and SN1 mechanisms begin with an identical rate-determining step that forms the carbocation. The formation of a carbocation is followed by a fast substitution or elimination step. For example, solvolysis of tert-butyl bromide in methanol at 50oC yields about a 2:1 ratio of substitution to elimination.

Hard and soft acid/base theory is discussed in more detail in Section 5.3, page 000.

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CH3 CH3 C CH3 Br

CH3OH 50 C
o

CH3 CH3 C CH3 tert-Butyl methyl ether 64% OCH3 +

CH3 C CH3 2-Methylpropene 36% CH2

However, adding methoxide ion, a stronger base, to the reaction mixture changes the yield to a 1:24 ratio of substitution to elimination. The elimination is an E2 mechanism, but substitution on a tertiary substrate does not readily occur via an SN2 mechanism and SN1 does not occur readily in base. Thus, there is only a small yield of the substitution product.
CH3 CH3 C CH3 Br CH3O CH3OH CH3 CH3 C CH3 4% OCH3
+

CH3 C CH3 96% CH2

Base size also affects the outcome of the elimination and substitution competition. The larger the base, the more the elimination reaction increases compared to the substitution reaction. A comparison of the reactions of methoxide and tert-butoxide ions with the tosylate of cyclohexanol at 50oC shows the effects of size.
OTs CH3O
o

OCH3 +

CH3OH, 50 C Cyclohexyl tosylate Methoxycyclohexane 54% OTs

Cyclohexene 46%

(CH3)3CO
o

OC(CH3)3 +

(CH3)3COH, 50 C Cyclohexyl tosylate tert-Butoxycyclohexane 0% Cyclohexene 100%

Exercise 13.4 Explain why chemists seldom use the azide and cyanide anions as bases in elimination reactions.

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Elimination reactions involve two carbons, whereas substitution reactions involve only one. Thus, in the transition states of both the E1 and E2 mechanisms, the charge disperses, or spreads out, more than it does in the transition states of the substitution reactions. When chemists decrease the solvent polarity of the reaction mixture, the elimination mechanism is favored compared to the substitution mechanism. As the temperature increases, the rate for an elimination reaction increases faster than the rate for a substitution reaction. This increase is true for both the unimolecular and bimolecular processes.
CH3 H3C C CH3 Br CH3CH2OH 25oC H3C CH3 C CH3 tert-Butyl ethyl ether 83% OCH2CH3 + H3C 2-Methylpropene 17% H3C C CH2

CH3 H3C C CH3 Br

CH3CH2OH 70oC H3C

CH3 C OCH2CH3 + CH3 (61%)

H3C C H3C (39%) CH2

Exercise 13.5 What are the possible products from the reaction of 2-chloro-2methylbutane with sodium hydroxide in aqueous ethanol? Which product would you expect to predominate at 25oC? Which product would you expect to predominate at 70oC? Although chemists have studied the E1 and SN1 mechanisms extensively for a number of years, most reactions of these types are of little practical use in organic synthesis. The problem is the inability to precisely control the outcome of the reactions. The lack of control is made worse by the competition between SN1 and E1 mechanisms under the same reaction conditions. In general, chemists try to avoid using a reaction with a carbocation intermediate in organic synthesis.

13.6 Summary of Elimination and Substitution

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This chapter and Chapter 12 present a number of factors that help place a particular reaction on the continuum of elimination and substitution reactions. Using tables, this section summarizes these factors. Table 13.2 compares the effects of various substrates on the outcome of the reaction. Table 13.3 shows how the nucleophile/base, the leaving group, the solvent and the temperature determine which mechanism a substrate will follow.
R R CH L R R C R L

CH3

CH2 L

Methyl 1o Bimolecular reactions only. SN2 only. Mainly SN2, but E2 with very strong or bulky base

2o 3o Bimolecular and unimolecular reactions. Mainly SN2 with weak bases or E2 with strong bases. Also SN1 or E1 in acid, especially if the substrate can rearrange. No SN2. In a solvolysis reaction, SN1 and E1. With a strong base, E2 predominates.

Table 13.2. Summary of reaction pathways of elimination and substitution reactions by substrate type.

Factor Nucleophile (base)

SN1 Poor Nucleophile

Leaving group. Solvent

E1 SN2 E2 Nucleophile Hard base Very poor nucleophile or is soft base very low concentration Weaker base than the nucleophile (base) Polar-protic solvent, lower polarity than for SN1 Polaraprotic solvent

Polar-protic solvent

Reaction temperature

Polaraprotic solvent, lower polarity than for SN2 Raising the temperature favors the elimination reaction

Table 13.3. Summary of effects of nucleophile (or base), leaving group, solvent, and reaction temperature on the mechanism of a particular substrate.

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Solved Exercise 13.2 Predict all reasonable products for each of the following reactions and determine the major product. Explain your choice. a) Br CH3O CH3OH, 0o Solution The reaction conditions are basic; thus, a carbocation cannot form. The reaction forms two possible products: one from an SN2 reaction and the other from an E2 reaction. Br OCH3 +

CH3O CH3OH, 0o

Because the substrate is a relatively open secondary substrate, an SN2 reaction proceeds readily. However, the nucleophile is a sufficiently strong base that an E2 reaction also proceeds readily. At 0oC, however, the amount of elimination is reduced significantly. b) CH3OH Br reflux

Solution A tertiary substrate does not readily undergo an SN2 reaction. Thus, this reaction must proceed via an SN1, E1, or E2 reaction mechanism. The SN1 and E1 are preferred because of the high temperature and weak base. The reaction forms three possible products. CH3OH Br reflux

OCH3 The ether is the major product because this is a solvolysis reaction. When a carbocation is produced, many solvent molecules are available to react with it.

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Exercise 13.6 Predict the product(s) of each of the following reactions. Indicate the mechanism for each one and the major and minor product. a)
Br CH3OH CH3 reflux

b)
Br KOH/ethanol CH3 reflux

c)
CH3CH2CHCH2CH3 Br CH3O CH3OH, 0o

d)
CH3CH2CHCH2CH3 Br NaI acetone

e)
CH2OTs CH CH OH 3 2 CH3 70oC

Sample Solution c)
CH3CH2CHCH2CH3 Br CH3O CH3OH, 0o CH3CH2CHCH2CH3 OCH3 SN2 major + CH3CH2CH E2 minor

CHCH3

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13.7 E & Z Nomenclature


Section 3.9 begins on page 000.

The Z comes from the German word for together, zusammen, and the E comes from the German word for opposite, entgegen. The Cahn-IngoldPrelog priority system is discussed in Section 11.2, page 000.

Section 3.9 introduces the terms cis and trans to describe the geometric relationship between groups on the double bond. However, in some cases these terms are insufficient and even confusing for describing the geometric relationships. A more general system uses the letters Z and E to describe cis and trans relationships. The E-Z method of naming is based on the Cahn-Ingold-Prelog system of substituent priorities. To determine whether a compound gets an E or a Z designation, assign each group bonded to the double bonded carbons a priority number. Using the condensed structural drawing of a molecule, assign the groups on the left a 1 and a 2, and assign the groups on the right a 1 and a 2. To determine which group gets which number, assign a 1 to the group with the atom having the higher atomic number closest to the point of attachment to the double bond. For example, consider cis- and trans-2-butene. Each carbon of the two double bonds has a methyl group and a hydrogen attached to it. The methyl group has the higher priority because carbon has a higher atomic number than hydrogen.

H3C H
C C

CH3 H

H C
3

H C C

CH3

Z-2-Butene (cis-2-Butene)

E-2-Butene (trans-2-Butene)

Number the methyl groups as #1 and the hydrogens as #2. When the #1 groups are on the same side of the bond, the molecule is the Z isomer. When the #1 are on opposite sides of the bond, the molecule is the E isomer. Both E and Z as well as cis and trans nomenclature are used interchangeably in disubstituted alkenes. The more complex alkenes use the E and Z terms. Exercise 13.7 Name the following alkenes using the E-Z system of nomenclature.

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a)
Cl C H C CH3 H

b)
CH3 CH3CH C CH3CH2CH2 C H CH2CH2CH3 C H C CH3 O CCH3

c)
CH3 CH3CH C H C CH2CH3 CH2OH

d)
Br

Sample solution a) E-1-Chloro-1-propene

13.8 Elimination of Organohalogens


Dehydrohalogenation is the loss of the elements H and X. H is a hydrogen, and X is a halogen. The result is a double bond.

Dehydrohalogenation was one of the earliest alkene forming reactions that chemists investigated. You have already seen many dehydrohalogenation examples in the illustrations of the elimination reactions. Most dehydrohalogenation reactions take place with alkoxide bases and at elevated temperatures. These conditions, as Section 13.5 discusses, favor the E2 elimination reaction mechanism.
Cl CH3CH2O CH3CH2OH Ethenylcyclohexane (Vinyl cyclohexane) (87%)

CH3CH2CH2CH2CH2Br

(CH3)3CO (CH3)3COH

CH3CH2CH2CH CH2 1-Pentene (85%)

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Br Br

(CH3)2CHO Diglyme 125oC 1,3-Cyclohexadiene (57%)

Nonnucleophilic amines are sufficiently basic to act as bases but do not act as a nucleophile. Generally, nonnucleophilic amines are sterically blocked or are tertiary.

Amines also function well as bases in elimination reactions. Amines are readily available in a variety of structures. The low basicity, or poor nucleophilicity, of some amines minimizes competing side reactions. In addition, amines are much more soluble in organic solvents than are the alkoxide bases. Both amines used in the following examples are nonnucleophilic.
Br + N N Cyclohexene (93%)

1,5-Diazabicyclo[4.3.0]5-nonene (DBN) Br CHCH3 + N Quinoline

CH

CH2

Ethenylbenzene (Styrene) (84%)

Vicinal substituents are substituents that are on adjacent carbon atoms.

A 1,2-dibromoalkane, which is a vicinal dibromide, gives an E2 reaction with potassium iodide in ethanol. The iodide ion is not sufficiently basic to remove a proton. Thus, the double bond forms between the two carbons bearing the bromine atoms.
Br

Br

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This reaction is one of the few reactions you will encounter in which the electrophile is not a proton. The reaction is also specific to the use of iodide ion. None of the other halide ions brings about this reaction. A stronger base, such as the tert-butoxide ion, forms a diene from the same substrate.
Br Br

(CH3)3CO

H Br
(CH3)3CO

Iodide ion functions as the base in the dehydrohalogenation of vicinal dibromides because iodine, like bromine, is soft. Thus, the bromine is polarizible and as the iodine approaches a bromine atom, the electrons shift easily toward the carbon. The use of the iodide ion is specific to vicinal dibromide reactions. The reaction of a 1,2-dibromoalkane with potassium iodide has limited value as a synthesis of an alkene because the major method of preparing a vicinal dihalide is from an alkene. Unlike the dehydrohalogenation, which forms a double bond at more than one possible position, the reaction of vicinal dihalides with potassium iodide forms the double bond only between the two carbons bearing the bromine. Exercise 13.8 Some chemists think that an alternate mechanism for the dehalogenation reaction with potassium includes a substitution step followed by an elimination step. Write a mechanism for this process. The reaction for the dehalogenation reaction of cis-1,2dibromocyclohexane with potassium iodide in ethanol is much slower than the reaction with the trans isomer. Does this experimental result fit with the alternate mechanism?
Geminal substituents are two substituents that are on the same carbon atom (1,1disubstituted).

1,2-Eliminations also form alkynes from both vicinal and geminal dihalides, as well as vinyl halides. This reaction follows the same kinetics and stereochemistry as the E2 reaction. A competing reaction is the formation of a diene. The reaction of 1,2dibromocyclohexane, shown at the beginning of this section to illustrate the dehydrohalogenation reaction, forms a diene because it has hydrogens available for elimination on the carbons adjacent to the bromines. The first reaction below is a very similar reaction, but it

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leads to an alkyne because it does not have hydrogens on adjacent carbons available for elimination to form a diene.
Br KOH CH3CH2OH Br Diphenylethyne (68%) C C

CH2CHBr2

NaNH2 NH3

CH

Ethynylbenzene (73%)

CH3CH2CH2 C H C

Cl CH3

KOH CH3CH2OH

CH3CH2CH2C 2-Hexyne (79%)

CCH3

Elimination reactions forming alkynes are usually slower than elimination reactions forming alkenes. In the same way that internal double bonds give more stable alkenes than terminal double bonds, internal triple bonds give more stable alkynes than do terminal triple bonds. Because the reaction requires stronger bases and higher temperatures, the triple bond has a tendency to migrate. Thus, a 1alkyne product frequently isomerizes to a 2-alkyne. This tendency to isomerize limits the utility of the reaction. However, the use of NaNH2 in liquid NH3 generally does not cause isomerization of the product because of low reaction temperature and the fact that the base reacts with the terminal alkyne forming its conjugate base. Nevertheless, chemists normally prefer to synthesize a terminal alkyne via a nucleophilic substitution instead of an elimination reaction. Under ideal reaction conditions, the E1 reaction, like the SN1 reaction, produces an excellent yield of a single product. However, ideal conditions rarely occur. Often the intermediate carbocations rearrange or give a mixture of products. Thus, chemists rarely use organohalogens as substrates in E1 reactions. Exercise 13.9

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Predict the product(s) of each of the following reactions. If more than one product is possible, indicate which is the major product. a)
CH3 CH3CCH2CH2CHBr2 CH3 NaNH2 NH3

b)
Br CHCH3 KOH Ethanol,

c)
Br CHCH3 (CH3)3CO DMSO,

d)
CH3CH2CH2CHCH2Br Br KI Ethanol

e)
CH3 CH3 CH3C Br CCH3 Br NaNH2 NH3

f)
CH3 Br DBN

Sample Solution d)
CH3CH2CH2CHCH2Br Br KI Ethanol CH3CH2CH2CH CH2

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13.9 Dehydration of Alcohols


Dehydration means the removal of water.

One of the most widely used elimination reactions is the dehydration of an alcohol to produce an alkene.
H

H2O

OH H

A dehydration reaction is reversible and usually has a small equilibrium constant. This means that the equilibrium favors the substrate and not the product. In fact, the reverse reaction is a method often used to synthesize alcohols. To improve the yields of a dehydration reaction, chemists heat the reaction mixture in the presence of a catalytic quantity of acid, to distill off the lower boiling product, either the water or the alkene, as it forms. This is a viable laboratory technique because the alkene has a lower boiling point than the alcohol. Tertiary and secondary alcohols react much faster than primary alcohols, suggesting that carbocation formation is the ratecontrolling step in the reaction. Primary carbocations are less stable than tertiary carbocations. Thus, the rate of reaction depends on the stability of the carbocation. The mechanism that dehydration reactions of tertiary and secondary substrates follow is E1.

C H

OH H

OH H

H2O

C H

H2O

Unless the carbocation can rearrange to become a more stable tertiary or secondary carbocation, primary carbocations do not form from the dehydration of primary alcohols. With a primary alcohol, the - OH group is a strong base and therefore a poor leaving group. As a result, alcohol dehydration does not occur in a basic reaction mixture.

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The first step in the dehydration of a primary alcohol is protonation of the OH group to form a good leaving group, OH2. At this point, the reaction follows a typical elimination reaction, and the conjugate base of the acid catalyst removes a hydrogen in an E2 mechanism. When the acid catalyst is sulfuric acid, the conjugate base is the HSO4 - ion.

O S
O

HO

O C

H C C C OH H

An alternate, and more common, reaction is a concerted rearrangement reaction. In a concerted rearrangement, the OH group is protonated as the hydride moves to the carbon atom bearing the protonated oxygen. This migration produces a more highly substituted, and thus more stable, carbocation than that which forms directly from the primary alcohol.
H H

H C H

H C H C

C OH H

The products of dehydration reactions using either 1-butanol or 2butanol as the substrate always contain the same mixture of alkenes. This indicates that the two reactions form the same carbocation intermediate. The following illustration shows how the dehydration reactions of two different substrates can give the same products.

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CH3CH2CH CH3CH2CH2CH2OH CH3CH2CHCH3 CH3CH2CHCH3 OH 1-Butene 30% + CH3CH

CH2

CHCH3

E- and Z-2-Butene 70%

The best acid catalysts for the alcohol dehydration reaction are concentrated sulfuric acid and phosphoric acid because they have a high affinity for water. Chemists usually choose phosphoric acid because it is less reactive and causes less decomposition of the reaction product. Using phosphoric acid is especially important when the boiling point of the alkene being formed is too high to readily distill from the reaction mixture. Acid-catalyzed dehydration reactions generally follow the Saytzeff rule in which the most substituted alkene predominates if two or more alkenes can form from the carbocation intermediate. Because carbocation rearrangements are common, the synthetic utility of alcohol dehydrations are limited to cases where no rearrangement is likely or where only one dehydration product is possible.

Synthesis of Cyclohexene
OH H3PO4/H2SO4

(90%)
Place 5.2 mL (0.05 mol) of cyclohexanol in a reaction flask. Add 1.0 mL of phosphoric acid along with 0.3 mL of sulfuric acid. Mix thoroughly and add a magnetic stir bar or a boiling stone. Heat until the product mixture begins to distill. Adjust the heat so that the rate of distillation is slowno more than 5-10 drops per minute. Continue heating until no more liquid distills off. Separate the water from the distillate and dry the organic layer over anhydrous sodium sulfate. Remove the drying agent and distill the product. Yield of cyclohexene is 3.7 g (90%), b.p. 82-84oC. Discussion Questions 1. What is the purpose of having a slow rate of distillation of product from the reaction mixture?

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Exercise 13.10 Propose a mechanism for the following reaction. Indicate the major product.
CH2OH H3PO4 CH2 + CH3 +

Exercise 13.11 Predict the major products for each of the following reactions. a)
CH3 CH3 CH CHCH3 OH H3PO4

b)
OH H3PO4

c)
OH CH3 CH3 H3PO4

d)
CH2OH H H2SO4

Sample Solution b)
OH H3PO4

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13.10 Pinacol Rearrangement


An acid-catalyzed dehydration of a 1,2-diol is frequently accompanied by a rearrangement of the carbon skeleton to form an aldehyde or ketone. This reaction is called the pinacol rearrangement. The pinacol rearrangement receives its name from the common name of the simplest compound that undergoes this rearrangement.
OH OH CH3 C C CH3 CH3 O CH3 C CH3 "Pinacolone" 3,3-Dimethyl-2-butanone (82%) C CH3

The pinacol rearrangement is a dehydration reaction of a vicinal diol accompanied by a rearrangement to form an aldehyde or ketone.

H2SO4

CH3 CH3 "Pinacol" 2,3-Dimethyl-2,3-butanediol

Because the substrate loses a molecule of water, the pinacol rearrangement is a form of dehydration reaction. The reaction follows these steps: 1) A proton from the acid protonates one of the OH groups. 2) The compound loses a molecule of water and forms a tertiary carbocation, much as would be expected from any tertiary alcohol. 3) A methyl group migrates from the carbon bearing the OH group to the carbon with the charge forming a resonance-stabilized carbocation that is even more stable than the original carbocation. 4) This carbocation loses a proton and forms the product.

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OH C

OH C CH3

OH OH

CH3

OSO3H

CH3

C CH3

CH3 CH3

CH3 CH3

OH C CH3

CH3

CH3CH3 CH3 O CH3 C CH3 HSO4


CH3 O

H CH3

CH3 O

H CH3

CH3 C CH3

CH3 C CH3

CH3

The Baeyer-Villiger reaction is discussed in Section 8.8, page 000.

The pinacol rearrangement has long been used as a model for the study of the rearrangement of a carbocation. Studies of the pinacol rearrangement show that the migratory aptitude for groups generally is H > aryl > alkyl. The best migrating groups are the most stable cations. Thus, a tertiary group migrates better than a primary group. Pinacol migratory aptitudes are different from those seen in the Baeyer-Villiger reaction. The migration in the pinacol rearrangement is stereospecific with the migrating group retaining its configuration. The actual migration depends on the substrate and the reaction conditions. For example, consider the reaction of 1,1diphenyl-2-methyl-1,2-propanediol. If it reacts with cold, concentrated H2SO4, the methyl group migrates. When it reacts with acetic acid plus a trace of H2SO4, the phenyl group migrates.

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CH3 H2SO4 CH3 CH3 OH OH (cold) (83%) O CH3COH H2SO4 (trace) O CH3 CH3 Phenyl migration CH3 O Methyl migration

(77%)

The difference is in the acid strength of the reaction medium. In stronger acid (H2SO4), the methyl-migration mechanism predominates. The driving force for the reaction is the stability of the carbocations in the solution. However, in weaker acid (CH3COOH), a concerted reaction occurs such that the group with the higher migratory aptitude (the phenyl group) is the one that actually moves. The mechanism for the concerted reaction begins with protonation of one of the OH groups. As the water molecule leaves, the migrating group simultaneously moves to form the protonated ketone.

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OH C CH3

OH C

O H OCCH3 CH3

OH C CH3

OH C

CH3

CH3 O

O CH3CO

CH3 O CH3 C C

CH3 C

Solved Exercise 13.3 Predict the major product from the following pinacol reactions. a) OH H2SO4

HO Solution Four equivalent alkyl groups can migrate in this reaction. Thus, the product is a spiro bicyclic product with a ketone on the larger ring. O OH H2SO4

HO b) OH OH H2SO4

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Solution This reaction has two possible migrating groups: a hydrogen from C1 and a methyl group from C2. Possible migrating groups or H CH3 CH3 OH H OH

The migratory aptitude of hydrogen is greater than for a methyl group, so the hydrogen migrates to form an aldehyde. O OH OH H2SO4 H

Exercise 13.12 Predict the major products for the following reactions. a)
OH H H OH H2SO4 (cold)

b)
OH OH H2SO4 (cold)

c)
CH2OH OH H2SO4 (cold)

d)

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OH

O CH3COH OH H2SO4 (trace)

Sample Solution c)
O CH2OH OH H2SO4 (cold) H

13.11 Hofmann Elimination


The Hofmann elimination reaction eliminates a quaternary ammonium hydroxide generally to form the least substituted alkene. The Wittig reaction is discussed in Section 7.10, page 000. The Hofmann orientation rule states that the least substituted alkene is synthesized. It is the opposite of the Markovnikov rule.

Formation of quaternary ammonium salts is discussed in Section 12.10, page 000.

The Hofmann elimination reaction has more historical importance in the development of organic chemistry than it has in modern synthesis. Chemists now prefer other reactions, such as the Wittig reaction, to the Hofmann elimination reaction. However, the mechanism of the Hofmann is still important to consider because it gives insight into the E2 mechanism. A. W. von Hofmann conducted the original experiments in 1851. Based on the understanding he gained from this experiment, he proposed what became known as the Hofmann orientation rule. The Hofmann reaction forms a quaternary ammonium salt from an amine (RNH2) and methyl iodide, then it eliminates trimethylamine and a proton to form an alkene. The amide ion itself ( - NH2) is not eliminated because, similar to the OH group, the NH2 group is not a very good leaving group. However, exhaustive methylation to form a quaternary ammonium group puts a positive charge on the nitrogen of the amine group making the neutral trialkylamine a very good leaving group. A Hofmann elimination reaction follows E2 kinetics. To accomplish the first step in a Hofmann elimination reaction, the conversion of the amine to the quaternary ammonium salt, chemists usually react the amine with an excess of methyl iodide.
R NH2 CH3I R N(CH3)3 I

Next they convert the tetraalkyl ammonium iodide to the hydroxide by treating it with silver oxide in water.

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N(CH3)3 I

Ag2O H2O

N(CH3)3

OH

If the quaternary ammonium hydroxide contains a hydrogen to the quaternary amine, then heating the compound to 150oC forms the alkene by loss of the neutral trimethylamine.
HO

H C C N(CH3)3 C C

The Hofmann reaction is an exception to the rule that an elimination reaction forms the more substituted alkene, the Saytzeff product. Instead, the Hofmann elimination of the quaternary ammonium hydroxide produces the least substituted alkene because the trimethylammonium group is too large to form the more substituted alkene. Its size interferes with the ability of the molecule to achieve the anti-coplanar arrangement required for the E2 mechanism to form the Saytzeff product.
CH3 CH3CH2C N(CH3)3 OH CH3 CH3 C CH3CH2 93% CH2
+

CH3 C H 7% C

CH3 CH3

Looking at the above example from a three-dimensional view helps you to see how the size of the trimethylamino group prevents significant production of the more substituted alkene. Figure 13.7 compares the conformation of the quaternary ammonium hydroxide required for an E2 elimination with a more stable conformation of the quaternary ammonium hydroxide by looking along the C2C3 bond. The direction of elimination for the Saytzeff product is an elimination at the C2C3 bond. The Hofmann elimination reaction results in elimination at the C1C2 bond.

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H H3C H CH3 CH3 N(CH3)3

H3C H Unstable gauche steric interaction

CH3

CH3

H N(CH3)3

Hydrogen not anti to leaving group

Needed for Saytzeff E2 product


(a)

More stable H H3C H CH2CH3 H N(CH3)3

Conformation for Hofmann E2 product (b)


Figure 13.7. Hofmann elimination yields the least substituted alkene because the quaternary ammonium group is too large to allow formation of the conformation needed for Saytzeff elimination. (a) Shows the conformations needed for the Saytzeff product. (b) Shows the conformation for the Hofmann elimination.

Nucleophilic substitution is a significant side reaction in many Hofmann eliminations. In the previous reaction, nearly 20% of the starting material undergoes an SN2 reaction on one of the methyl groups attached to the nitrogen to produce methanol and N,N,2trimethyl-2-butanamine.
CH3 CH3CH2C N(CH3)3 CH3 OH CH3 CH3CH2C N(CH3)2 CH3 N,N,2-Trimethyl-2-butanamine + CH3OH Methanol

Exercise 13.13 Explain the differences between the reactions of the following isomers.

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(CH3)3C

N(CH3)3

OH

(CH3)3C

N(CH3)2 100%

CH3OH

N(CH3)3 OH (CH3)3C + (CH3)3C 91%

N(CH3)2
+

(CH3)3C 9%

CH3OH

13.12 Oxidation of Alcohols


With the exception of the pinacol rearrangement (Section 13.9), all the reactions discussed so far in this chapter are elimination reactions that form alkenes or alkynes. This section discusses another exception: the elimination of two hydrogen atoms from a primary or secondary alcohol to form an aldehyde or ketone. This elimination reaction is called an oxidation reaction.
O RCH

In an oxidation reaction, a molecule typically loses two hydrogens to form a multiple bond.

RCH2OH

Oxidation (-2H)

O RCHOH R Oxidation (-2H) RCR

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A chromate oxidation uses chromic acid or chromium trioxide to oxidize primary or secondary alcohols to carboxylic acids or ketones. This reaction is often called the Jones oxidation.

Many procedures are available to accomplish an oxidation reaction, but this book covers only a few. A common one is the chromate oxidation. A chromate oxidation uses chromium trioxide or chromic acid to oxidize secondary alcohols to ketones.
CrO3 H2SO4, acetone

OH

O Cycloheptanone (97%)

OH Na2Cr2O7 H2SO4, H2O

2-Pentanone (91%)

The mechanism for a chromate oxidation involves the initial formation of a chromate ester. The chromate ester then undergoes an E2 type elimination to form the carbonyl group.
O OH H Cr O O H H O CrO3H H OSO3H O O H OH
O C

Cr O

Hydrate formation is discussed in Section 7.5, page 000.

When starting from a secondary alcohol, the product is a ketone. When starting from primary alcohol, the product is an aldehyde. With the aqueous acid in the reaction mixture, the aldehyde forms a hydrate. This hydrate can react further to form a carboxylic acid.
O H3O H HO H OH Like above mechanism O OH

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O H CrO3 H2SO4, acetone

O OH 3-Methylbutanoic acid (93%)

To oxidize primary alcohols to carboxylic acids, chemists use either chromium trioxide or sodium dichromate.
O OH CrO3 H2SO4, acetone Pentanoic acid (91%) OH

Oxidation of double and triple bonds is discussed in Section 14.10, page 000.

A drawback of chromate oxidation is the reaction conditions can oxidize other functional groups such as double or triple bonds. Pyridinium chlorochromate (PCC), however, is a much milder oxidizing agent than chromic acid. In addition, no water is present so it cannot oxidize an aldehyde to a carboxylic acid. PCC is synthesized by reacting equal amounts of pyridine, chromium trioxide, and HCl.
CrO3 HCl N

ClCrO3 N H Pyridinium chlorochromate (PCC)

Pyridine

PCC is quite soluble in low polarity solvents. The most commonly used solvent is methylene chloride (CH2Cl2), which is specific for the oxidation of primary and secondary alcohols to aldehydes and ketones.
O OH PCC CH2Cl2 Hexanal (81%) H

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O OH PCC CH2Cl2 3,7-Dimethyl-6-octenal (93%) H

Synthesis of Citronellal
H3C H PCC Alumina OH H O H3C H

(93%)
Pyridinium chlorochromate on alumina Dissolve 0.6 g of chromium trioxide in 1.1 mL of 6 M hydrochloric acid. Slowly add 0.47 g of pyridine maintaining the temperature of the reaction mixture at 45oC. Cool the mixture to 10oC to initiate crystal formation, then reheat to 40oC to dissolve the crystals formed. To the resulting solution, add 5 g of alumina with stirring. Remove the solvent on a rotary evaporator and dry the orange solid for 2 hours in a vacuum at room temperature. Store this reagent under vacuum in the dark until use. Yield about 6.3 g of PCC on alumina. Citronellal Place the PCC on alumina synthesized above in a 50 mL Erlenmeyer flask and add 546 mg (3.5 mmol) of citronellol and 10 mL of hexane. Stir this mixture for up to 3 hours. Follow the course of the reaction by using thin layer chromatography (TLC) plates. Determine when the reaction is complete by the disappearance of the citronellol spot in a TLC plate using methylene chloride as eluant. Filter off the solid and wash it three times with 5 mL portions of ether. Combine the ether washes with the hexane filtrate. Evaporate the combined solvents using a rotary evaporator. The yield of product is 500 mg (93%); the b.p. is 204-207oC. Discussion Questions 1. TLC is a convenient way to follow the course of the synthesis of citronellal, but can you think other methods for following the course of the reaction? If so, what do you see that would help you know when the reaction is complete?

Exercise 13.14 Predict the major products for the following reactions.

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a)
OH CrO3 H2SO4, acetone

b)
OH PCC CH2Cl2

c)

O OH

PCC CH2Cl2

d)
OH

Na2Cr2O7 H2SO4, H2O

Sample Solution b)
OH PCC CH2Cl2 O H

Key Ideas from Chapter 13

A 1,2-elimination, or -elimination, reaction involves the loss of a leaving group and an electrophile from adjacent atoms in a substrate. This loss results in the formation of a bond.

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There are two major elimination mechanisms: E1 and E2. In the E1 mechanism, the leaving group departs from the substrate, then the electrophile leaves. The reaction proceeds via a carbocation intermediate. In the E2 mechanism, the electrophile and leaving groups depart at the same time in a concerted reaction. Both E1 and E2 mechanisms proceed best on tertiary substrates. An E1 mechanism loses all the stereochemistry at the reaction site due to the formation of a symmetrical carbocation intermediate. An E2 mechanism requires that the leaving group and electrophile be in the same plane. The rate of reaction for the anti-coplanar conformation is generally much higher than for the syn-coplanar conformation. Most E1 and E2 elimination reactions follow the Saytzeff rule for forming a double bond. The most highly substituted alkene is generally the most stable product, so it is the major product. A reaction following the Saytzeff rule is a regioselective reaction. A measurement of alkene stability is the amount of heat evolved when a particular alkene is hydrogenated. The less heat given off when adding hydrogen to a double bond, the more stable the double bond. E1 and SN1 reactions work best in acidic conditions with a polar-protic solvent and a tertiary substrate. An E2 reaction usually works best in strongly basic conditions with a large base, a less polar solvent, and a tertiary substrate. E1 takes preference over SN1 when the base is very weak or is present in very low concentrations. Both pathways form the same reactive carbocation. SN1 takes preference over E1 when a good nucleophile is present or is present in moderate to high concentrations. A large or hard base increases the rate of E2 over SN2.

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Increasing solvent elimination.

polarity

favors

substitution

over

Increasing the temperature increases the rate of elimination over substitution. Alkyl halides readily eliminate via an E2 mechanism to form an alkene. Chemists often use vicinal dihalides to form an alkene regiospecifically. A strong base reacts with a vicinal dihalide to form a diene or an alkyne, depending on the stereochemistry of the substrate. A geminal dihalide also forms an alkyne. The E and Z prefixes are used in preference to the trans and cis prefixes in the IUPAC nomenclature rules. Alcohols dehydrate to form alkenes. Most dehydration reactions follow the E1 mechanism. The carbon skeleton commonly rearranges. The Hofmann elimination forms an alkene from a quaternary ammonium hydroxide. The product is usually the least substituted alkene following the Hofmann orientation. Elimination can also take place with a primary or secondary alcohol. This reaction produces an aldehyde or carboxylic acid from a primary alcohol and a ketone from a secondary alcohol.

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5 July 2005