CHAPTER 7Haloalkanes

• Haloalkane (alkyl halide): a compound containing a halogen covalently bonded to an sp3 hybridized carbon; given the symbol RX

Timberlake LecturePLUS 1999 3

Haloalkanes

An alkane in which one or more H atoms is replaced with a halogen (F, Cl, Br, or I)

CH3Br 1-bromomethane Br (methyl bromide)

CH3CH2CHCH3 2-bromobutane

Cl chlorocyclobutane

Nomenclature - IUPAC– locate the parent alkane– number the parent chain to give the substituent

encountered first the lower number– show halogen substituents by the prefixes fluoro-,

chloro-, bromo-, and iodo- and list them in alphabetical order with other substituents

– locate each halogen on the parent chain

3-Bromo-2-methyl-pentane

12

34

5Br

4-Bromocyclohexene

1

23

4

56Br

OH

Cltrans-2-Chloro-cyclohexanol

4

56

123

Nomenclature– examples

• Common names: name the alkyl group followed by the name of the halide

Br

2-Bromo-4-methyl-pentane

1234

54-Bromo-

cyclohexene

1

234

56

trans-2-Chloro-cyclohexanol

Br Cl

OH

Br Cl Cl

2-Bromobutane(sec-Butyl bromide

Cnhloroethene(Vinyl chloride)

3-Chloropropene(Allyl chloride)

Nomenclature– several polyhaloalkanes are common solvents and

are generally referred to by their common or trivial names

– hydrocarbons in which all hydrogens are replaced by halogens are commonly named as perhaloalkanes or perhaloalkenes

CHCl3CH2Cl2 CCl2=CHClCH3CCl3 Dichloromethane(Methylene chloride)

Trichloromethane (Chloroform)

Trichloroethyne (Trichlor)

1,1,1-Trichloroethane (Methyl chloroform)

PerchloroethylenePerfluoropropanePerchloroethane

C CCl

ClClCl

ClCl

F C C C FF

F

F

F

F

F ClC C

Cl

ClCl

Timberlake LecturePLUS 1999 7

Name the following:Br

Cl

Cl

Timberlake LecturePLUS 1999 8

Name the following:

bromocyclopentane

1,3-dichlorocyclohexane

Br

Cl

Cl

SN2 – Substitution Nucleophilic, Bimolecular • This is called a concerted reaction– Meaning that the bond breaking and the bond

forming occur simultaneously• Is classified as bimolecular– Because both the haloalkane and the nucleophile

are involved in the rate determining step. – S = substitution– N = nucleophilic– 2 = bimolecular (two species are involved in the

rate-determining step)

Recall

• Nucleophile (nucleus loving): An electron rich species that seeks a region of low electron density (Nu).

• Electrophile (electron loving): A low electron-density species that seeks a region of high electron density.

SN2 – Substitution Nucleophilic, Bimolecular

C XNu CNu X

The nucleophile attacks the reactive center from the side opposite the leaving group; in other words it involves a backside attack by the nucleophile.

nucleophilicsubstitution

Nucleophile++ C NuC XNu - X-

leavinggroup

SN2

– both reactants are involved in the transition state of the rate-determining step

– the nucleophile attacks the reactive center from the side opposite the leaving group

C BrH

HH

HO + C

H

H H

HO Br- -

Transition state withsimultaneous bond breaking

and bond forming

CH

HH

HO + Br -

C Cl:

CH3

H....

SN2 ANIMATION ENERGY PROFILE

R

Press the slide show button to see the animation. Press ESC to finish.

C Cl:

CH3

H:Br:....

..

..

SN2 ANIMATION ENERGY PROFILE

R

C Cl:

CH3

H:Br:....

..

..

SN2 ANIMATION ENERGY PROFILE

R

C Cl:

CH3

H....:Br:

..

..

SN2 ANIMATION ENERGY PROFILE

R

C Cl:

R

CH3

H....:Br:

..

..

SN2 ANIMATION ENERGY PROFILE

CR

CH3H

:Br.... Cl:

..

..

SN2 ANIMATION ENERGY PROFILE

ActivatedComplex

Transition State

- -

C:Br....

CH3

H:Cl:....

SN2 ANIMATION ENERGY PROFILE

R

C:Br....

CH3

H:Cl:....

SN2 ANIMATION ENERGY PROFILE

R

C:Br....

CH3

H:Cl:....

SN2 ANIMATION ENERGY PROFILE

R

C:Br....

CH3

H

SN2 ANIMATION ENERGY PROFILE

R

SN1 – Substitution Nucleophilic, Unimolecular

– S = substitution– N = nucleophilic– 1 = unimolecular (only one species is involved in

the rate-determining step)

SN1 – Substitution Nucleophilic, Unimolecular • In this reaction the bond breaking between carbon

and the leaving group is entirely completed before bond forming with the nucleophile begins

• This is classified as unimolecular– Only the haloalkane is involved in the rate-

determining step – In other words, only the haloalkane contributes to

the rate law governing the rate determining step

SN1

• Step 1: ionization of the C-X bond gives a carbocation intermediate

C

CH3

CH3H3C

+C

H3C

H3CBr

H3C

slow, ratedetermining

A carbocation intermediate; carbon is trigonal planar

+ Br

SN1

– Step 2: reaction of the carbocation (an electrophile, low electron density) with methanol (a nucleophile, high electron density) gives an oxonium ion

– Step 3: proton transfer completes the reaction

CH3OH H3C

C

CH3

CH3

OCH3

H

CCH3

CH3

CH3O

H3C

H H3CH3C

CH3C

OCH3

H

fast ++ ++

++++ fastC

H3CH3C

OH3C

OCH3

HOHO

CH3CH3

H

H

CH3

H3CCH3C

H3C

SN1

• For an SN1 reaction at a stereocenter, the product is a racemic mixture

(R)-EnantiomerPlanar carbocation (achiral)

CH

Cl

C6H5

Cl

C+

C6H5

H

Cl

CH3OH-Cl-

-H+

SN1– the nucleophile attacks with equal probability

from either face of the planar carbocation intermediate

+

A racemic mixture

Cl

C6H5 C6H5

C OCH3H

CH3O CH

Cl(R)-Enantiomer(S)-EnantiomerPlanar carbocation

(achiral)

C+

C6H5

H

Cl

CH3OH-H+

SN2 and SN1

• Are competing constantly, what determines what mechanism is a reaction going to prefer?1.The structure of the nucleophile2.The structure of the haloalkane3.The leaving group4.The solvent

1. The structure of the nuceophile

• Refer to table 7.2 page 228 from your book to see the types of nucleophiles we deal with most commonly in this semester.

• Nucleophilicity: a kinetic property measured by the rate at which a Nu attacks

Nucleophilicity

• Table 7.2

good

poor

Br-, I -

HO-, CH3O-, RO-CH3S-, RS-

H2OCH3OH, ROH

CH3COH, RCOHO O

NH3, RNH2, R2NH, R3NCH3SH, RSH, R2S

Effectiveness Nucleophile

moderateCH3CO-, RCO-

O O

2. Structure of the Haloalkane

• SN1 reactions – governed by electronic factors, namely the relative

stabilities of carbocation intermediates– relative rates: 3° > 2° > 1° > methyl

• SN2 reactions– governed by steric factors, namely the relative

ease of approach of the nucleophile to the site of reaction

– relative rates: methyl > 1° > 2° > 3°

SN1

• SN1 will be favored if a tertirary carbocation is involved, sometimes if a secondary carbocation is involved

• SN1 will never be favored if a primary cabocation or methyl are involved

SN2

• The less crowded site will always favor the SN2 mechanism

• Will be favored if it involves a primary carbocation and methyl

• Sometimes will be favored if a secondary carbocation is involved

3.Leaving group• Chlorine ion, bromine ion and Iodine ion make good

leaving groups because of their size and Electronegativity help to stabilize the resulting negative charge

• The ability of a group to function as a leaving group is related to how stable is as an anion

• The most stable anion and the best leaving groups are the conjugate bases of strong acids!!!

I- > Br- > Cl- >> F- > CH3CO- > HO- > CH3O- > NH2-

Greater ability as leaving group

Greater stability of anion; greater strength of conjugate acid

Rarely act as leaving groups in nucleophilic substitution and -elimination reactions

O

4. The Solvent• Protic solvent: a solvent that contains an -OH

group – these solvents favor SN1 reactions; the greater the

polarity of the solvent, the easier it is to form carbocations in it

CH3COOHCH3CH2OHCH3OHHCOOHH2OStructure

Acetic acid

Formic acid

EthanolMethanol

Water

ProticSolvent

Polarity of Solvent

4. The Solvent• Aprotic solvent:does not contain an -OH group – it is more difficult to form carbocations in aprotic

solvents– aprotic solvents favor SN2 reactions

(CH3CH2)2OCH2Cl2

OCH3CCH3

OCH3SCH3

Diethyl etherDichloromethane

AproticSolvent Structure

Dimethyl sulfoxide (DMSO)

Acetone

Polarity ofSolvent

Summary of SN1 and SN2

CH3X

RCH2X

R2CHX

R3CX

Type of HaloalkaneMethyl

Primary

Secondary

Tertiary

SN2 SN1

Substitutionat a stereocenter

SN2 is favored. SN1 does not occur. The methylcation is so unstable that it is never observed in solution.SN1 does not occur. Primary carbocations are so unstable thatthey are never observed in solution.SN1 is favored in protic solventswith poor nucleophiles.

SN2 is favored in aproticsolvents with goodnucleophiles.SN2 does not occur becauseof steric hindrance aroundthe substitution center.

SN1 is favored because of the ease of formation of tertiary carbocations.

Inversion of configuration.The nucleophile attacksthe stereocenter from theside opposite the leavinggroup.

Racemization. The carbocationintermediate is planar, and attack bythe nucleophile occurs with equalprobability from either side.

SN2 is favored.

Elimination reactions• Dehydrohalogenation– These reaction require forcing conditions like a

strong base and heat.• (Hydroxide ion or ethoxide ion)

– Halogen is removed from one carbon of a haloalkane– And the hydrogen from the adjacent carbon– To form a double bond • (an alkene)

-Elimination• Zaitsev rule: the major product of a -

elimination is the more stable (the more highly substituted) alkene

Br CH3CH2O-Na+

CH3CH2OH2-Methyl-2-butene (major product)

2-Bromo-2-methylbutane

2-Methyl-1-butene

+

Br CH3O-Na+

CH3OH +

1-Methyl-cyclopentene

(major product)

1-Bromo-1-methyl-cyclopentane

Methylene-cyclopentane

E1 and E2 mechanisms

• There are both examples of beta-elimination reactions– The difference is the timing of the bond-breaking

and the bond-forming steps.• E1 stands for elimination and 1 for

unimolecular• E2 stands for elimination and 2 for

bimolecular

E1

• The breaking for the halogen carbon bond has to be completely broken before any reaction occurs with the base

• This is the slow determining step (the breaking of the halogen carbon bond)

E1 Mechanism– Step 1: The breaking for the halogen carbon bond

gives a carbocation intermediate

– Step 2: proton transfer from the carbocation intermediate to a base (in this case, the solvent) gives the alkene

CH2-C-CH3

Br

CH3CH3-C-CH3

CH3

Br –slow, rate

determining+

(A carbocation intermediate)

+

HO

H3CH-CH2-C-CH3

CH3HO

H

H3CCH2=C-CH3

CH3fast+

+ ++

E2

• The base removes a beta hydrogen at the same time that carbon halogen bond is broken

• The rate of the reaction will depend both on the haloalkane and the base

• The stronger the base the more likely it is that the E2 mechanism will be in operation

E2 Mechanism

• A one-step mechanism; all bond-breaking and bond-forming steps are concerted

CH3CH2OCH3

H-CH-CH2-Br

CH3CH2O-H CH3CH=CH2 Br

+

+ +

Table 7.6

• E2 is favored if you are dealing with a primary haloalkane

• E2 is favored for secondary haloalkane if you have a really strong base

• E1 is favored for secondary haloalkane if you have weak bases

• E1 is favored for tertiary haloalkanes.