1 chapter 8 alkyl halides and elimination reactions

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Chapter 8

Alkyl Halides and Elimination reactions

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Alkyl Halides and Elimination Reactions

General Features of Elimination

It is well known that elimination reactions (E) often compete successfully with SN reactions, because nucleophiles are also Brønsted-Lowry bases (SN2 versus E2) and carbocations are prone to the elimination of a proton (again involving a Brønsted-Lowry base: SN1 versus E1).

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• Removal of the elements HX is called dehydrohalogenation.

• Dehydrohalogenation is an example of elimination

(1,2-elimination).


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• bases used in elimination reactions : RO¯ ( alkoxides).


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• How to draw any product of dehydrohalogenation

1. Find the carbon.

2. Identify all carbons with H atoms.

3. Remove the elements of H and X from the and carbons and form a bond.


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Alkenes—The Products of Elimination

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


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• rotation about double bonds is restricted.


diastereomers

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

Stability of Alkenes

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

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

• Consequently, increasing the number of electron donating groups on a carbon atom able to accept electron density makes the alkene more stable.


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• There are two mechanisms of elimination—E2 and E1, just as there are 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 cleavage and bond formation, analogous to the SN2 and SN1 mechanisms.

• E2 and SN2 reactions have some features in common, as do E1 and SN1 reactions.

Mechanisms of Elimination

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• The most common mechanism for dehydrohalogenation

• second-order kinetics : both the alkyl halide and the base appear in the rate equation, i.e.,

Mechanisms of Elimination—E2

rate = k[(CH3)3CBr][¯OH]

• One step mechanism : all bonds are broken and formed in a single step. -- The reaction is concerted

C

CH3

CH3

CH3

BrOH

_

C

CH3

CH3

CH2 + +H2O Br_

E2 mechanism

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

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

• E2 reactions are generally run with strong, negatively charged bases like¯OH and ¯OR. Strong sterically hindered (non-nucleophilic) nitrogen bases (DBN and DBU) are also sometimes used.


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N N.. ..

DBN DBUN N....

1,5-diazabicyclo[4.3.0]non-5-ene and 1.8-diazobicylco[5.4.0]undec-7-ene

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Mechanisms of Elimination—E2 : the leaving group

the solvent

Acetone, DMF, DMSO

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Substitution v.s. elimination

Mechanisms of Elimination—E2 : nature of R group

i.e. more substitution lowers Ea

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Alkyl Halides and Elimination ReactionsMechanisms of Elimination—E2

slower

faster

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Table 8.2 summarizes the characteristics of the E2 mechanism.


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

• This phenomenon is called the Zaitsev rule. (1875)

The Zaitsev (Saytzeff) Rule

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• The Zaitsev rule: the major product in elimination has the more substituted double bond.

• A reaction is regioselective when it yields predominantly or exclusively one constitutional isomer when more than one is possible. Thus, the E2 reaction is regioselective.

The Zaitsev (Saytzeff) Rule

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If the stereochemistry is known, the outcome is not always the same.

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• When a mixture of stereoisomers is possible from a dehydrohalogenation, the major product is the more stable stereoisomer.

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

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

cf. stereoselective

Why?

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• In the transition state of an E2 reaction all involved atoms should be aligned in the same plane.

one hydrogen atom, two carbon atoms, the leaving group (X)

There are two ways 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 is all about orbital alignment.

This arrangement allows the molecule to react in the lower energy staggered conformation, and allows the incoming base and leaving group to be further away from each other.

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• In cyclic compounds, the stereochemical requirement of an anti periplanar geometry in an E2 reaction has important consequences.


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

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Alkyl Halides and Elimination ReactionsStereochemistry of the E2 Reaction

• The cis isomer

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• The trans isomer. Stereochemistry of the E2 Reaction

This is not predicted by the Zaitsev rule.

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If the stereochemistry is known, the outcome is not always the same.

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• An E1 reaction exhibits first-order kinetics:

Mechanisms of Elimination— E1 mechanism

rate = k[(CH3)3CCI]

• The E1 reaction proceeds via a two-step mechanism: the bond to the leaving group breaks first before the bond is formed. The slow step is unimolecular, involving only the alkyl halide.

_+ ++ IH3O

H2O

C CH2

CH3

CH3

C

CH3

CH3 CH3

I

E1 mechanism

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E1 Mechanisms _+ ++ IH3O

H2O

C CH2

CH3

CH3

C

CH3

CH3 CH3

I

E1 mechanism

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

Other characteristics of E1 reactions

• The strength of the base usually determines whether a reaction follows the E1 or E2 mechanism. Strong bases like ¯OH and ¯OR favor E2 reactions, whereas weaker bases like H2O and ROH favor E1 reactions.


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

• Zaitsev’s rule applies to E1 reactions also.

E1 Mechanisms

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Table 8.3 summarizes the characteristics of the E1 mechanism.


No need of antiperiplanar arrangement

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• SN1 and E1 reactions have exactly the same first step—formation of 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 E2 reactions.

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SN1 and E1 Reactions

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• 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 bond of an alkene. Two consecutive elimination reactions produce two bonds of an alkyne.

E2 Reactions and Alkyne Synthesis

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

• Two different starting materials can be used—a vicinal dihalide or a geminal dihalide.


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• Stronger bases are needed to synthesize alkynes by dehydrohalogenation than are needed to synthesize alkenes.

• Because sp2 hybridized C—H bonds are stronger than sp3 hybridized C—H bonds. As a result, a stronger base is needed to cleave this bond.

• The typical base used is ¯NH2 (amide), used as the sodium salt of NaNH2. KOC(CH3)3 can also be used with DMSO as solvent.


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

H3CH2C Br

NaI

MeOHt-BuOH

t-BuOK

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• Good nucleophiles that are weak bases favor substitution over elimination —Certain anions generally give products of substitution because they are good nucleophiles but weak bases. These include I¯, Br¯, HS¯, ¯CN, and CH3COO¯.


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


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Tertiary Alkyl Halides

C

CH3

CH3

CH3

Br

C

CH3

CH3

CH3

OC2H5

C

CH3

CH3

CH3

OC2H5

CH2C

CH3

CH3

and

CH2C

CH3

CH3

and

C2H5O-Na+

C2H5OH

C2H5OH

heat

2-bromo-2-methyl--propane

2-ethoxy-2-methylpropane

2-methylpropene

3% 97%

80% 20%

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Tertiary Alkyl Halides

E2 will occur preferentially if a strong base is used (OH-, OR-). Reaction in neutral (weakly basic) conditions leads to a mixture of SN1 and E1 products, with usually the SN1 product favored.

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Primary Alkyl Halides

SN2 is favored by use of a good nucleophile (RS-, I-, CN-, Br-) and polar aprotic solvent. E2 is favored by use of a strong, hindered base (tert-butoxide).

1-butene (85%)pentanenitrile (90%) 1-bromobutane

t-BuO-K+Na+CN-

THF-HMPACH3CH2CH CH2CH3CH2CH2CH2 BrCH3CH2CH2CH2 CN

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Secondary Alkyl Halides

SN2 and E2 compete. If a weakly basic strong nucleophile (CH3COO-, Br-, I-) and polar aprotic solvent is used, SN2 dominates. If a strong base (OR-) in a protic solvent is used, E2 is dominant.

CH3CHCH3

BrCH3CHCH3

OOCCH3

CH3CHCH3

OC2H5

CH3CH CH2CH3CH CH2

CH3COO-Na+

DMSO

2-bromopropane

2-propyl acetate

propene

(100%)

(0%)

C2H5O-Na+

C2H5OH

2-ethoxypropane (20%)

propene (80%)

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Secondary Alkyl Halides

If only a weak nucleophile or base is present then SN1 competes with E1 and it is difficult to predict which will be favored.

This is a situation that is best avoided.

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8.18, 8.22, 8.24, 8.31, 8.33, 8.40, 8.41, 8.45, 8.49, 8.50,

8.53, 8.54, 8.57

Homework

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Preview of Chapter 9

Alcohols, Ethers and Epoxides

Preparation of alcohols, ethers, and epoxidesSynthesize an alcohol and an ether from alkylhalide.

Reactions of alcohols, ethers and epoxidesWhat is dehydration reaction?What is 1,2-hydride shift?What reagents are used to convert alcohols into halides?

1 chapter 8 alkyl halides and elimination reactions

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