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
5
CH3 I
iodomethane
4
3
CH3
2
CH3
1
CH3 CH2 CH CH CH3
CI
3-chloro-2-methylpentane
6
5
4
CH3 CH2 C
CH3
3
2
1
CH2 CH CH3
Br
4-bromo-2,4-dimethylhexane
no. of alkyl groups: 2
H
R' C X
R
Classification of alkyl halides
a) Primary (1 )
c) Tertiary (3o)
no. of alkyl groups: none or one
no. of alkyl groups: 3
o
H
H C X
H
H
H C X
R
o
b) Secondary (2 )
no. of alkyl groups: 2
H
R' C X
R
c) tertiary (3o)
no. of alkyl groups: 3
R''
R' C X
R
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:
RMM
bp (°C)
CH3F
34
-78
CH3Cl
50.5
-24
CH3Br
95
4
CH3I
142
42
- compounds with branched have more spherical
shapes, have smaller surface area, resulting lower
boiling points.
CH3
CH3
CH3CH2CH2CH2Cl
bp 78 oC
CH3 C Cl
CH3CH2CHCl
CH3
bp 67 oC
o
bp 52 C
- alkyl halides with more carbon atoms have higher
boiling points.
CH3Cl
o
bp -24 C
CH3CH2Cl
bp 12oC
CH3CH2CH2Cl
o
bp 47 C
• 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
dry ether
CH3-CH3 + 2NaI
reflux
• Most suitable for preparation of higher alkanes
containing an even number of carbon atoms.
• 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 byproducts.
CH3I + 2Na + CH3CH2I
dry ether
CH3CH2CH3 + 2NaI + CH3CH2-CH2CH3 + CH3CH3
by-products
Reactions of alkyl halides
• Two types of reactions:
i) substitution reactions
ii) elimination reactions
a) nucleophilic substitution
C C
Nuc
H X
-
X
C C
-
H Nuc
b) elimination
B
-
C C
H X
B-H
C
C
X
-
NUCLEOPHILIC SUBSTITUTION REACTIONS
1) Formation of alcohol
OH
R-X
R-OH
X
nucleophile
example
CH3CH2 Br
CH3CH2 OH
NaOH
ethyl bromide
NaBr
ethyl alcohol
2) Williamson ether synthesis
R-X
R'O
R-O-R'
X
nucleophile
example
CH3 I
CH3CH2 O Na+
methyl iodide
CH3CH2 OH
sodium ethoxide
Na
CH3 O CH2CH3
ethyl methyl ether
CH3CH2 O Na+
sodium ethoxide
Na+ I-
3) Amine synthesis
R-X
NH3
nucleophile
example
CH3CH2 Br
H-NH2
ethyl bromide
R-NH2
HX
CH3CH2 NH2
HBr
ethylamine (primary amine)
HBr(g) + NH3 (g)
NH4Br (s)
amine are also act as nucleophile (more reactive than ammonia)
C2H5Br
H N C2H5
H
C2H5Br
(C2H5)2NH
(C2H5)2NH + HBr
diethylamine
(secondary amine)
(C2H5)3N + HBr
triethylamine
(tertiary amine)
C2H5Br
(C2H5)3N
(C2H5)4N+ Brtetraethylammonium bromide
(quaternary salt)
4) Nitrile synthesis
R-X
CN
cyanide
(nucleophile)
H2O/H+
R-CN
H2/Ni
180oC
X
R-CN
nitrile
R-COOH (hydrolysis)
R-CH2NH2 (reduction)
example
(CH3)2CHCH2CH2-Cl
NaCN
4-methylpentanenitrile
1-chloro-3-methylbutane
H2O/H+
(CH3)2CHCH2CH2-CN
(CH3)2CHCH2CH2-CN
H2/Ni
180oC
(CH3)2CHCH2CH2-COOH
(CH3)2CHCH2CH2-CH2NH2
NaCl
Mechanism of nucleophilic substitution
reactions
H
δδ+
R C X
Nu
-
H
H
R C Nu
X
-
H
EXAMPLE
H
OHδ+
δCH3 C Br
H
formation of alcohol
CH3
H
C OH
H
-
Br
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.
(CH3)3C-Br + OH-
slow
(CH3)3C-OH + Br-
MECHANISM OF SN1 REACTION
STEP 1: FORMATION OF CARBOCATION
(CH3)3C
Br
slow
(CH3)3C+
+
Br
very reactive
STEP 2: NUCLEOPHILIC ATTACK
(CH3)3C+
+ OH-
fast
(CH3)3C-OH
-
rate limiting step
• 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, 2bromo-3-methylbutane, yields the tertiary alcohol, 2-methyl-2butanol.
CH3 H
CH3 H
CH3
C
C
H
Br
CH3
SN1
CH3
H2O
C
o
C
CH3
Br-
H
slow step
(2 carbocation)
2-bromo-3-methylbutane
shift of H
CH3 H
CH3
C
C
CH3 H
CH3
H
o
(3 carbocation)
H-OH
fast
CH3
C
C
CH3
OH H
2-methyl-2-butanol
• Reactivity towards SN1 substitution
mechanisms follows the stability of
carbocations:
SN1 reactivity: 3o > 2o > 1o > CH3X
retention
inversion
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)
HO
H δ+
δC I
H
H
HO C
iodomethane
transition state
H
δ-
H
δ+ δ-
I
H
H
-
I
HO C
H
methanol
H
or
HO
CH3
I
iodomethane
HO
CH3
I
transition state
HOCH3
methanol
-
I
rate-limiting
step
• 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.
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
Rate of reaction First order
SN2
Second order
Stereochemistry Racemic mixture
Complete
(mixture of inversion inversion
and retention)
Reactivity
Benzyl > allyl > ~ 3o CH3X > 1o > 2o > 3o
> 2o > 1o
Nucleophiles
Weak nucleophiles
Strong
nucleophiles
Elimination reactionsdehydrohalogenation 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.
C C
H X
alkyl halide
HX = HCl or HBr or Hl
C C
alkene
HX
• 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 reaction
ii) 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
MECHANISM OF E1 REACTION
STEP 1: FORMATION OF THE CARBOCATION (RATE LIMITING)
C
C
C
H
X
H
C
X
STEP 2: A BASE ABSTRACTS A PROTON (FAST)
B
C
H
C
B-H
C
C
E2(Elimination, bimolecular) reaction
•
•
•
•
A second order reaction.
Rate equation: k[RX][Base]
E2 reactivity: 3o > 2o > 1o
Mechanism:
B
H
C C
C
X
C
B-H
X-
Comparison E1 and E2 reactions
E1
Rate of reaction First order
E2
Second order
Reactivity
3o > 2o > 1o
3o > 2o > 1o
Base
Do not need strong
base
Strong base
Alkyl halides
1O
Reactions
RCH2X
2O
NuSN2
RCH2Nu
Nu- strong
SN2 + E2
R2CHNu +
alkene
R2CHX
B- (strong)
alkene
E2
Nu- (weak)
SN1 + E1
3O
R3CNu +
alkene
R3CX
B- (strong)
E2
alkene
SOME COMMON NUCLEOPHILES
strong nucleophiles moderate nucleophiles weak nucleophiles
(CH3CH2)3P
S-H
I
(CH3CH2)2NH
C N
(CH3CH2)2N
H-O
CH3-O
Br
NH3
F
H-O-H
CH3-S-CH3
Cl
O
CH3C O
CH3 O H
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 carbonmetal 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 DiphenylTrichloroethane) is used as insecticides.