alkyl halides and elimination reactions - iowa state … halides and elimination reactions...

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Alkyl Halides and Elimination Reactions

• Elimination reactions involve the loss of elements from the startingmaterial to form a new π bond in the product.

General Features of Elimination


• Equations [1] and [2] illustrate examples of elimination reactions. Inboth reactions a base removes the elements of an acid, HX, from theorganic starting material.


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• Removal of the elements HX is called dehydrohalogenation.

• Dehydrohalogenation is an example of β elimination.

• The curved arrow formalism shown below illustrates how fourbonds are broken or formed in the process.



• The most common bases used in elimination reactions arenegatively charged oxygen compounds, such as HO¯ and its alkylderivatives, RO¯, called alkoxides.


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• To draw any product of dehydrohalogenation:

1) Find the α carbon.

2) Identify all β carbons with H atoms.

3) Remove the elements of H and X form the α and β carbons andform a π bond.


Alkyl Halides and Elimination Reactions• To draw any product of dehydrohalogenation:

1) Find the α carbon.

2) Identify all β carbons with H atoms.

3) Remove the elements of H and X form the α and β carbons andform a π bond.

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• Recall that the double bond of an alkene consists of a σ bond and aπ bond.

Alkenes—The Products of Elimination


• Alkenes are classified according to the number of carbon atomsbonded to the carbons of the double bond.


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• Recall that rotation about double bonds is restricted.



• Recall that rotation about double bonds is restricted.


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• Because of restricted rotation, two stereoisomers of 2-butene arepossible.

• cis-2-Butene

• trans-2-butene

• cis-2-Butene and trans-2-butene are diastereomers, becausethey are stereoisomers that are not mirror images of each other.



• Whenever the two groups on each end of a carbon-carbon doublebond are different from each other, two diastereomers are possible.


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• In general, trans alkenes are more stable than cis alkenes becausethe groups bonded to the double bond carbons are further apart,reducing steric interactions.


• The stability of an alkene increases as the number of R groupsbonded to the double bond carbons increases.


• The higher the percent s-character, the more readily an atomaccepts electron density. Thus, sp2 carbons are more able to acceptelectron density and sp3 carbons are more able to donate electrondensity.

• Consequently, increasing the number of electron donating groupson a carbon atom able to accept electron density makes the alkenemore stable.

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• trans-2-Butene (a disubstituted alkene) is more stable than cis-2-butene (another disubstituted alkene), but both are more stable than1-butene (a monosubstituted alkene).


Overall Relative Stabilities of AlkenesThe greater the number of attached alkyl groups (i.e.

the more highly substituted the carbon atoms of thedouble bond), the greater the alkene’s stability

geminal

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Geminal: substituents that are on the same atom

CH3

CH3

Vicinal: substituents that are on adjacent atoms

Cl

Cl

H

Cl

CH3 CH3 Cl Cl

Cl H


• There are two mechanisms of elimination—E2 and E1, just as thereare two mechanisms of substitution, SN2 and SN1.

• E2 mechanism—bimolecular elimination

• E1 mechanism—unimolecular elimination

• The E2 and E1 mechanisms differ in the timing of bond cleavageand bond formation, analogous to the SN2 and SN1 mechanisms.

• E2 and SN2 reactions have some features in common, as do E1 andSN1 reactions.

Mechanisms of Elimination

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• The most common mechanism for dehydrohalogenation is the E2mechanism.

• It exhibits second-order kinetics, and both the alkyl halide and thebase appear in the rate equation i.e.

Mechanisms of Elimination—E2

rate = k[(CH3)3CBr][¯OH]

• The reaction is concerted—all bonds are broken and formed in asingle step.

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• There are close parallels between E2 and SN2 mechanisms in howthe identity of the base, the leaving group and the solvent affect therate.

• The base appears in the rate equation, so the rate of the E2 reactionincreases as the strength of the base increases.

• E2 reactions are generally run with strong, negatively chargedbases like¯OH and ¯OR.

• Two strong sterically hindered nitrogen bases called DBN andDBU are also sometimes used.


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• The SN2 and E2 mechanisms differ in how the R group affects thereaction rate.


• The increase in E2 reaction rate with increasing alkyl substitutioncan be rationalized in terms of transition state stability.

• In the transition state, the double bond is partially formed.

• Increasing the stability of the double bond with alkylsubstituents stabilizes the transition state.

• i.e. lowers Ea, which increases the rate of the reactionaccording to the Hammond postulate.


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• Increasing the number of R groups on the carbon with the leavinggroup forms more highly substituted, more stable alkenes in E2reactions.

• In the reactions below, since the disubstituted alkene is more stable,the 30 alkyl halide reacts faster than the 10 alkyl halide.



Table 8.2 summarizes the characteristics of the E2 mechanism.


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• Recall that when alkyl halides have two or more different β carbons,more than one alkene product is formed.

• When this happens, one of the products usually predominates.

• The major product is the more stable product—the one with themore substituted double bond.

• This phenomenon is called the Zaitsev rule.

The Zaitsev (Saytzeff) Rule

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• The Zaitsev rule: the major product in β elimination has the moresubstituted double bond.

• A reaction is regioselective when it yields predominantly orexclusively one constitutional isomer when more than one ispossible. Thus, the E2 reaction is regioselective.



• When a mixture of stereoisomers is possible from adehydrohalogenation, the major product is the more stablestereoisomer.

• A reaction is stereoselective when it forms predominantly orexclusively one stereoisomer when two or more are possible.

• The E2 reaction is stereoselective because one stereoisomer isformed preferentially.


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• The dehydrohalogenation of (CH3)3CI with H2O to form (CH3)C=CH2

can be used to illustrate the second general mechanism ofelimination, the E1 mechanism.

• An E1 reaction exhibits first-order kinetics:


rate = k[(CH3)3CI]

• The E1 reaction proceed via a two-step mechanism: the bond to theleaving group breaks first before the π bond is formed. The slowstep is unimolecular, involving only the alkyl halide.

• The E1 and E2 mechanisms both involve the same number of bondsbroken and formed. The only difference is timing. In an E1, theleaving group comes off before the β proton is removed, and thereaction occurs in two steps. In an E2 reaction, the leaving groupcomes off as the β proton is removed, and the reaction occurs inone step.

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• The rate of an E1 reaction increases as the number of R groupson the carbon with the leaving group increases.


• The strength of the base usually determines whether a reactionfollows the E1 or E2 mechanism. Strong bases like ¯OH and ¯ORfavor E2 reactions, whereas weaker bases like H2O and ROHfavor E1 reactions.

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• E1 reactions are regioselective, favoring formation of themore substituted, more stable alkene.

• Zaitsev’s rule applies to E1 reactions also.



Table 8.3 summarizes the characteristics of the E1 mechanism.


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• SN1 and E1 reactions have exactly the same first step—formationof a carbocation. They differ in what happens to the carbocation.

SN1 and E1 Reactions

• Because E1 reactions often occur with a competing SN1 reaction,E1 reactions of alkyl halides are much less useful than E2reactions.


• The transition state of an E2 reaction consists of four atomsfrom an alkyl halide—one hydrogen atom, two carbon atoms,and the leaving group (X)—all aligned in a plane. There are twoways for the C—H and C—X bonds to be coplanar.

Stereochemistry of the E2 Reaction

• E2 elimination occurs most often in the anti periplanar geometry.This arrangement allows the molecule to react in the lowerenergy staggered conformation, and allows the incoming baseand leaving group to be further away from each other.

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• The stereochemical requirement of an anti periplanar geometryin an E2 reaction has important consequences for compoundscontaining six-membered rings.

• Consider chlorocyclohexane which exists as two chairconformers. Conformer A is preferred since the bulkier Cl groupis in the equatorial position.


• For E2 elimination, the C-Cl bond must be anti periplanar to theC—H bond on a β carbon, and this occurs only when the H andCl atoms are both in the axial position. The requirement for transdiaxial geometry means that elimination must occur from theless stable conformer, B.

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• Now consider the E2 dehydrohalogenation of cis- and trans-1-chloro-2-methylcyclohexane.


• This cis isomer exists as two conformers, A and B, each ofwhich as one group axial and one group equatorial. E2 reactionmust occur from conformer B, which contains an axial Cl atom.

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• Because conformer B has two different axial βhydrogens, labeled Ha and Hb, E2 reaction occurs in twodifferent directions to afford two alkenes.

• The major product contains the more stabletrisubstituted double bond, as predicted by the Zaitsevrule.



• The trans isomer of 1-chloro-2-methylcyclohexane existsas two conformers: C, having two equatorial substituents,and D, having two axial substituents.


• E2 reaction must occur from D, since it contains an axial Clatom.

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• Because conformer D has only one axial β H, E2 reaction occursonly in one direction to afford a single product.

• This is not predicted by the Zaitzev rule.



• The strength of the base is the most important factor in determiningthe mechanism for elimination.

• Strong bases favor the E2 mechanism.

• Weak bases favor the E1 mechanism.

When is the Mechanism E1 or E2

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• A single elimination reaction produces a π bond of an alkene. Twoconsecutive elimination reactions produce two π bonds of analkyne.

E2 Reactions and Alkyne Synthesis

• Two elimination reactions are needed to remove two moles of HXfrom a dihalide substrate.

• Two different starting materials can be used—

• vicinal dihalide

• geminal dihalide


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• Stronger bases are needed to synthesize alkynes bydehydrohalogenation than are needed to synthesize alkenes.

• The typical base used is ¯NH2 (amide), used as the sodium salt ofNaNH2. KOC(CH3)3 can also be used with DMSO as solvent.



• Stronger bases are needed for this dehydrohalogenation becausethe transition state for the second elimination reaction includespartial cleavage of the sp2 hybridized C—H bond.

• sp2 hybridized C—H bonds are stronger than sp3 hybridizedC—H bonds.


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• Good nucleophiles that are weak bases favor substitution overelimination—Certain anions always give products of substitutionbecause they are good nucleophiles but weak bases.

• These include I¯, Br¯, HS¯, and CH3COO¯.

Predicting the Mechanism from the Reactants—SN1,SN2, E1 or E2.

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• Bulky nonnucleophilic bases favor elimination oversubstitution—KOC(CH3)3, DBU, and DBN are too sterically hinderedto attack tetravalent carbon, but are able to remove a small proton,favoring elimination over substitution.




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Predicting the Mechanism from the Reactants—SN1, SN2, E1or E2.

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