ORGANIC CHEMISTRY CHM 207

CHAPTER 5:ALKYL HALIDES

NOR AKMALAZURA JANI

SUBTOPICS

• Nomenclature and structures of alkyl halides.• Classification of alkyl halides.• Physical properties of alkyl halides.• Reaction of alkyl halides.

1) Formation of alkanes (Wurtz reaction)

2) Nucleophilic substitution reaction:

i) Example: formation of alcohol, Williamson ether synthesis, amine synthesis, nitrile synthesis

ii) Mechanism of nucleophilic substitution reactions.

iii)Types of nucleophilic substitution reaction: SN1 and SN2 reaction.

3) Elimination reaction (dehydrohalogenation of alkyl halides).

- E1 and E2 reactions.

• Uses of alkyl halides.

ALKYL HALIDES

• General formula: CnH2n+1X where n = 1,2,… and X (halogen)

• Functional group: halogen, -X (X = F, Cl, Br, I)

• Naming alkyl halides: - same as nomenclature of alkanes

CH3 ICH3 CH2 CH

CI

CH

CH3

CH3 C CH2 CH CH3

CH3

Br

CH3

CH2CH3

iodomethane 3-chloro-2-methylpentane

12345 12345

4-bromo-2,4-dimethylhexane

6

Classification of alkyl halides

PHYSICAL PROPERTIES• BOILING POINTS

- molecules with higher molecular weight have higher boiling points.- reasons: the molecule is heavier, slower moving, have greater surface area, have larger London attractions, resulting higher boiling points.- example:

CH3F CH3Cl CH3Br CH3IRMM 34 50.5 95 142 bp (°C) -78 -24 4 42

- compounds with branched have more spherical shapes, have smaller surface area, resulting lower boiling points.

CH3CH2CH2CH2Cl CH3CH2CHCl

CH3 CH3 C

CH3

CH3

Cl

bp 78 oC bp 67 oC bp 52 oC

- alkyl halides with more carbon atoms have higher boiling points.

CH3Cl CH3CH2CH2Clbp -24oC bp 12oC bp 47oC

CH3CH2Cl

• DENSITIES

- alkyl fluoride and alkyl chlorides (with one Cl atom) are less dense than water.- alkyl chloride with two or more chlorine atoms are denser than water.- all alkyl bromides and alkyl iodides are denser than water.

REACTIONS OF ALKYL HALIDES

Formation of alkanes (Wurtz reaction)

• Equation:

2R-X + 2Na → 2NaX + R-R

• Example:

2CH3I + 2Na CH3-CH3 + 2NaI

• Most suitable for preparation of higher alkanes containing an even number of carbon atoms.

dry ether

reflux

• Alkanes containing an odd number of carbon atoms can be prepared by using a mixture of two different alkyl halides.

• This reaction produces only low yields due to the formation of other alkanes as by-products.

CH3I + 2Na + CH3CH2I CH3CH2CH3 + 2NaI + CH3CH2-CH2CH3 + CH3CH3

dry ether

by-products

Reactions of alkyl halides

• Two types of reactions:

i) substitution reactions

ii) elimination reactions

C

H

C

X

C

H

C

X

B-H

C

H

C

Nuc

C C

a) nucleophilic substitution

Nuc - X -

b) elimination

B - X -

NUCLEOPHILIC SUBSTITUTION REACTIONS

R-X OH

CH3CH2 Br NaOH

R-X

CH3 I CH3CH2 O Na+

R-OH

R-O-R'

CH3CH2 OH

X

X

CH3 O CH2CH3

NaBr

Na+ I-

1) Formation of alcohol

example

ethyl bromide ethyl alcohol

2) Williamson ether synthesis

R'O

example

methyl iodide sodium ethoxide ethyl methyl ether

nucleophile

nucleophile

CH3CH2 O Na+

sodium ethoxide

CH3CH2 OH Na

R-X

CH3CH2 Br H-NH2

R-NH2

CH3CH2 NH2 HBr

3) Amine synthesis

example

ethyl bromide ethylamine (primary amine)

NH3 HXnucleophile

HBr(g) + NH3 (g) NH4Br (s)

amine are also act as nucleophile (more reactive than ammonia)

C2H5Br H N

H

C2H5 (C2H5)2NH + HBrdiethylamine(secondary amine)

(C2H5)2NHC2H5Br (C2H5)3N + HBrtriethylamine(tertiary amine)

C2H5Br (C2H5)3N (C2H5)4N+ Br-

tetraethylammonium bromide(quaternary salt)

R-X CN

(CH3)2CHCH2CH2-Cl NaCN

R-CN X

(CH3)2CHCH2CH2-CN NaCl

4) Nitrile synthesis

cyanide (nucleophile)

nitrile

example

1-chloro-3-methylbutane 4-methylpentanenitrile

R-CN

H2O/H+

R-COOH (hydrolysis)

H2/Ni

180oCR-CH2NH2 (reduction)

(CH3)2CHCH2CH2-CN

H2O/H+

H2/Ni

180oC

(CH3)2CHCH2CH2-COOH

(CH3)2CHCH2CH2-CH2NH2

Mechanism of nucleophilic substitution reactions

R C

H

X

H

Nu-

R C

H

Nu

HX-

EXAMPLE

CH3 C

H

Br

HCH3 C

H

OH

H

OH-

Br-

formation of alcohol

δ-

δ-

δ+

δ+

Type of nucleophilic substitution reactions: SN1

and SN2 reactions

• S = substitution• N = nucleophilic• 1 = a first order (unimolecular) reaction• 2 = a second order (bimolecular) reaction

SN1 (Substitution, Nucleophilic, unimolecular)

reactions• Unimolecular : only one molecule involved in the transition state

of the rate-limiting step.• Example: the reaction between aqueous NaOH and tertiary alkyl

halides.

OH-

(CH3)3C Br

OH-

Br-

Br-(CH3)3C-Br + (CH3)3C-OH +slow

MECHANISM OF SN1 REACTION

STEP 1: FORMATION OF CARBOCATION

(CH3)3C+ +slow

rate limiting step

STEP 2: NUCLEOPHILIC ATTACK

(CH3)3C+ + fast

very reactive

(CH3)3C-OH

• The reaction is first order and the rate depends only on the concentration of the tertiary alkyl halides.

Rate = k[(CH3)3CBr]

• The concentration of OH- does not have any effect on the rate of reaction.

• OH- does not involved in the rate-limiting step.

Carbocation rearrangement in SN1 reactions

• Rearrangement of the carbon skeleton will take place if a more stable carbocation can be formed in the process.

• For example, hydrolysis of the secondary alkyl bromide, 2-bromo-3-methylbutane, yields the tertiary alcohol, 2-methyl-2-butanol.

CH3 C C

CH3 H

BrH

CH3

SN1

H2O

CH3 C C

CH3 H

CH3

H

CH3 C C

CH3 H

H

CH3

H-OH

Br-

CH3 C C

CH3 H

CH3

HOH

(2o carbocation)slow step

(3o carbocation)

shift of H

fast

2-methyl-2-butanol

2-bromo-3-methylbutane

• Reactivity towards SN1 substitution mechanisms follows the stability of carbocations:

SN1 reactivity: 3o > 2o > 1o > CH3X

inversionretention

SN2 (Substitution, Nucleophilic, bimolecular) reactions

• The processes of bond breaking and bond forming occur simultaneously (one bond is forming, one bond is breaking).

• The mechanism involves only one step.

• For example, hydrolysis of iodomethane (primary alkyl halides)

C IH

HH

HOC I

H

HH

HO CH

HH

HO I-

iodomethane transition state methanol

δ-δ+δ+δ- δ-

• A second order reaction• Rate equation = k[CH3I][OH-]• Both iodomethane and the OH- are involved in the

rate-limiting step.• SN2 reactivity: CH3 X > 1o

> 2o > neopentyl > 3o

• Factor that determines the order of reactivity in SN2 reactions is the steric effect.

• A steric effect is one in which the rate of chemical reaction depends on the size or spatial arrangement of the groups attached to, or near to, the reaction site of the molecule.

HO CH3 I HO CH3 I HOCH3 I-

iodomethane transition state methanol

rate-limitingstep

or

Relative reactivities of primary, secondary, and

tertiary alkyl halides• The reactivity of alkyl halides towards nucleophilic

substitution depend on the halogen.

• The rate of reaction decrease in the order R-I > R-Br > R-Cl > R-F

(most reactive) (least reactive)

• Reason: C-X bond become stronger from I to F

Comparison SN1 and SN2 reactions

SN1 SN2

Rate of reaction First order Second order

Stereochemistry Racemic mixture (mixture of inversion and retention)

Complete inversion

Reactivity Benzyl > allyl > ~ 3o > 2o > 1o

CH3X > 1o > 2o

> 3o

Nucleophiles Weak nucleophiles Strong nucleophiles

Elimination reactions-dehydrohalogenation of alkyl

halides• Elimination: loss of two atoms or groups from the

substrate to form a pi bonds.

• Dehydrohalogenation (removal of hydrogen and a halogen atom) of alkyl halide to form alkene.

• The elimination reaction is occurred when the reaction used strong base for examples, t-butoxide ion ((CH3)3CO-) or OH- ion and heated at high temperature.

• Dehydrohalogenation will yield an alkene that has the larger number of alkyl groups as the main product (Saytzeff’s rule).

• Elimination reactions can be divided into two:i) E1 reactionii) E2 reaction

E1(Elimination, unimolecular) reaction

• The rate-limiting state involves a single molecular than a collision between two molecules.

• A first order reaction.

• Rate equation: k[RX]

• E1 reactivity: Benzyl > allyl > 3o > 2o > 1o

B

C C

XH

C C

H

C C

H

B-H

X

C C

MECHANISM OF E1 REACTION

STEP 1: FORMATION OF THE CARBOCATION (RATE LIMITING)

STEP 2: A BASE ABSTRACTS A PROTON (FAST)

E2(Elimination, bimolecular) reaction

• A second order reaction.• Rate equation: k[RX][Base]• E2 reactivity: 3o > 2o > 1o • Mechanism:

B

C C

X

H

C C B-H X-

Comparison E1 and E2 reactions

E1 E2

Rate of reaction First order Second order

Reactivity 3o > 2o > 1o 3o > 2o > 1o

Base Do not need strong base

Strong base

Alkyl halides Reactions

1O RCH2X RCH2NuNu-

SN2

R2CHX

R2CHNu + alkene

alkene

Nu- strongSN2 + E2

E2

B- (strong)

2O

R3CX

R3CNu + alkene

alkene

Nu- (weak)SN1 + E1

E2

B- (strong)

3O

(CH3CH2)3P

S-H

I

(CH3CH2)2NH

C N

H-O

CH3-O

(CH3CH2)2N

strong nucleophiles

CH3-S-CH3

Cl

NH3

Br

CH3C O

O

moderate nucleophiles

F

weak nucleophiles

H-O-H

CH3 O H

SOME COMMON NUCLEOPHILES

USES OF ALKYL HALIDES• Solvents

- industrial and household solvents.- carbon tetrachloride (CCl4) used for dry cleaning, spot removing.- methylene chloride (CH2Cl2) is used to dissolve the caffeine from coffee beans to produce decaffeinated coffee.

• Reagents- as starting materials for making complex molecules.- for example, the conversion of alkyl halides to organometallic reagents (compounds containing carbon-metal bonds) is important tool for organic synthesis.

• Anesthetics

- examples: chloroform (CHCl3) and ethyl chloride.

• Freons: Refrigerants and foaming agents- Freons (called chlorofluorocarbons, or CFCs) is used as a refrigerant gas.

• Pesticides- example: DDT (Dichloro Diphenyl-Trichloroethane) is used as insecticides.