Chapter 9: Elimination Reactions of Alkyl Halides:

Competition between Substitutions and

Eliminations

GoalsAfter this chapter, you should be able to:

Predict products of E2 and E1 reactionsDetermine stereochemistry of E2/E1 ProductsDetermine whether SN2, SN1, E1 or E2 will occur

What is an SN2 Reaction?SN2 mechanism; S for substitution, N for nucleophilic and 2 because two molecules collide at the critical point in the reaction.

Review: An SN2 Reaction

Stereochemistry of Inversion

If the nucleophile and the leaving group are both high in the R/S priority order, this means that an R alkyl halide gives an S product, and vice-versa

Energy of Inversion

Energy of Inversion

With SN2, Size of Substituent Groups

Matters

Relative Reactivity Toward SN2tertiary < secondary < primary < methyl

Kinetics of Nucleophilic Substitution

Rate = k[RBr][Nu-]Second order kinetics

Effect of Bond Strength of the Leaving Group on SN2

ReactivitySince the carbon-halogen bond strength increases up the periodic table the relative SN2 reactivity of the alkyl halide is:

RF < RCl < RBr < RITosO- is a better leaving group than

I-

OH-, NH2-, and RO- are worse than F-

Nucleophilicity:

CH3CO2 (-) < Cl(-) < Br(-) < N3

(-) < CH3O(-) < CN(-) < I(-) < SCN(-) < CH3S

(-)

NucleophilicityParallels basicity

H2O < C2H3O2- < OH-

Increases down the periodic tableI- < Cl- < F-

Anions are more nucleophilic than neutral compoundsThe solvent matters!

Solvent EffectsConsider KBr as a nucleophile sourceProtic solvents with –OH, -NH slow SN2 rxn

These solvents cluster around the nucleophile lowering the effective nucleophilicity

Polar aprotic solvents speed SN2

These solvents cluster around the metal ion of the salt freeing the nucleophile to be nucleophilic.

Characteristics of SN2 Reactions

Single Step MechanismInversion of configuration SN2 reactions are generally reliable only when the alkyl halide is primaryHalogen is generally Cl or Br since

C-F bond is too strongC-I bond is weak and compounds are unstable

An SN2 Reaction

SN1 ReactionsSN1 reactions proceed by a two step mechanism

First: Leaving group leaves giving a carbocation

Second: Nucleophile attacks carbocation

R

C

R

BrR

R

C

R

+ Br-R

R

C

R

R + H2O

R

C

R

R OH + H+

Review: An SN1 Reaction

SN1 Reactions

H

C

H

BrH

R

C

H

BrH

R

C

R

BrH

R

C

R

BrR< < <

Relative Reactivity Toward SN1

Leaving GroupsOH- < NH2

-<RO- F - < Cl - < Br - < I < TosO-

Susceptibility to leaving

Evidence for SN1 KineticsThe reaction rate is only dependent upon the concentration of the substance with the leaving group

R-X R+ + X- is a slow = rate determining

Racemic mixtures are usualCarbocation formation

Rate = k[R-X] where X is leaving group

SN1 Reaction RatesDepend on stability of the carbocation

More stable carbocation=faster reaction

-CH3 < 1° < 2° < 3°

Relative Stability of Carbocation

H2C CCH2

HCH2

The Nucleophile and SN1

NO EFFECT!

R

C

R

BrR

R

C

R

RFAST

R

C

R

R

R

C

R

R OH + H+

+ Br-

+ H2O

SLOW

Energy for SN1

Solvent Effects on SN1Polar solvents stabilize the intermediate carbocation.

R

C

R

R O

H

H

OH

HO

H

H

OH

H

Summary SN1Fastest with

Compounds that form stable carbocationGood leaving groupNucleophiles that are not basic to prevent competing elimination reactionsPolar solvents

An SN1 Reaction

Elimination ReactionsZaitsev’s Rule:

Base induced elimination reactions generally give the more highly substituted double bond alkene product

H3C C

H

H3C Br

CH3

H

H3C C

H

H3C

CH2

H

H3CC

H3C

CH3

H

An E2 Reactions

E2 ReactionsSingle step attack of nucleophile on hydrogen on carbon adjacent to the carbon containing the leaving group.

H3C C

H

H3C Br

CH3

H

H3C C

H

H3C

CH2

H

H3CC

H3C

CH3

H

E2 KineticsThe rate of the reaction is dependent upon the concentration of the compound containing the leaving group and the nucleophile base.Rate = k[RX][Base]

Geometry of E2All atoms involved are in same planeThe hydrogen and leaving group are anti

H3C C C

H

H3C Br

CH3

H

Cycloalkane E2: What do you expect?

Br

H

RKOH

BrHR

KOH

E2 ReactionBr

H

RKOH

BrHR

KOH

R

No Reaction

An E2 Reactions

Zaitsev’s Rule LimitationsDon’t use for conjugated double bonds.You can trick the reaction into favoring the least substituted alkene by using a Bulky base.

C

Br

CH2

C H3

C H3

CH3C

C H3

O–

CH3

C H3

+

Zaitsev’s Rule LimitationsDon’t use for conjugated double bonds.You can trick the reaction into favoring the least substituted alkene by using a Bulky base.

CH

C H3C

C H3

CH3

CH2

C H3C

C H3

CH2

C

Br

CH2

C H3

C H3

CH3C

C H3

O–

CH3

C H3

+

E1 ReactionsFirst step is identical to SN1 – Elimination of the leaving group giving a carbocationFirst step is slow and rate determiningSecond step is the attack of a hydrogen on a carbon adjacent to the carbocationRacemic mixtures are usual

The E1 Reaction

E1 KineticsRate = k[R-X]

CH3

C

CH3

H3C BrCH3

C

CH3

H3C + Br-

CH3

C

CH3

H3C Br

CH3

C

CH2

H3C

H

HO

H

CH3

C

CH2

H3C

E

Nucleophile Anionic Nucleophiles(Weak Bases)(RS-, SCN-, I-, Br-, N3

-, CN- etc.)

Anionic Nucleophiles(Strong Bases: HO-, RO-)

Neutral Nucleophiles(H2O, ROH, RSH, R3N)

Alkyl Group

Primary

RCH2-

Rapid SN2 substitution. The rate may be reduced by substitution of -carbons, as in the case of neopentyl.

Rapid SN2 substitution. E2 elimination may also occur.e.g. ClCH2CH2Cl   + KOH ___> CH2=CHCl

SN2 substitution. (N S >>O)

Secondary

R2CH-

SN2 substitution plus E2 elimination (depends on basicity of the nucleophile). The rate of substitution may be reduced by branching at the -carbons, and this will increase elimination.

E2 elimination will dominate. SN2 substitution. (N S >>O)In high dielectric ionizing solvents, such as water, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be formed slowly.

Tertiary

R3C-

E2 elimination will dominate with most nucleophiles (even if they are weak bases). No SN2 substitution due to steric hindrance. In high dielectric ionizing solvents, such as water, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be expected.

E2 elimination will dominate. No SN2 substitution will occur. In high dielectric ionizing solvents SN1 and E1 products may be formed.

E2 elimination with nitrogen nucleophiles (they are bases). No SN2 substitution. In high dielectric ionizing solvents SN1 and E1 products may be formed.

Allyl

H2C=CHCH2-

Rapid SN2 substitution for 1° and 2°-halides. For 3°-halides a very slow SN2 substitution or, if the nucleophile is moderately basic, E2 elimination. In high dielectric ionizing solvents, such as water, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be observed.

Rapid SN2 substitution for 1° halides (note there are no hydrogens. E2 elimination will compete with substitution in 2°-halides, and dominate in the case of 3°-halides. In high dielectric ionizing solvents SN1 and E1 products may be formed.

Nitrogen and sulfur nucleophiles will give SN2 substitution in the case of1° and 2°-halides. 3°-halides will probably give E2 elimination with nitrogen nucleophiles (they are bases). In high dielectric ionizing solvents SN1 and E1 products may be formed. Water hydrolysis will be favorable for 2° & 3°-halides.

Benzyl

C6H5CH2-

Rapid SN2 substitution for 1° and 2°-halides. For 3°-halides a very slow SN2 substitution or, if the nucleophile is moderately basic, E2 elimination. In high dielectric ionizing solvents, such as water, dimethyl sulfoxide & acetonitrile, SN1 and E1 products may be observed.

Rapid SN2 substitution for 1° halides (note there are no hydrogens. E2 elimination will compete with substitution in 2°-halides, and dominate in the case of 3°-halides. In high dielectric ionizing solvents SN1 and E1 products may be formed.

Nitrogen and sulfur nucleophiles will give SN2 substitution in the case of1° and 2°-halides. 3°-halides will probably give E2 elimination with nitrogen nucleophiles (they are bases). In high dielectric ionizing solvents SN1 and E1 products may be formed. Water hydrolysis will be favorable for 2° & 3°-halides.