Organic Chemistry

244 CHEM

Organic Halogen
Compounds
Dr. Hany El-Hamshary

5
Classes of Organohalogen Compounds (Organohalides):
1) Alkyl halides: a halogen atom is bonded to an sp3-hybridized carbon.

CH2Cl2 CHCl3 CH3I CF2Cl2

dichloromethane trichloromethane iodomethane dichlorodifluoromethane

methylene chloride chloroform methyl iodide Freon-12

2) Vinyl halides: a halogen atom is bonded to an sp2-hybridized carbon.

3) Aryl halides: a halogen atom is bonded to an sp2-hybridized
aromatic carbon.

C C X
X
2
A vinylic halide A phenyl halide or aryl halide
Examples of 1°, 2°, and
3° alkyl halides

3
 Importantance of Organohalogen Compounds

a) Solvents: Alkyl halides are used as solvents for relatively non-polar

compounds:
CCl4, CHCl3, CCl3CH3, CH2Cl2, ClCH2CH2Cl, and etc.

b) Reagents:
• Alkyl halides are used as the starting materials for the synthesis of many
compounds.
• Alkyl halides are used in nucleophilic reactions, elimination reactions,
formation of organometallics,.and etc.
c) Refrigerants: Freons (ChloroFluoroCarbon)

d) Pesticides: DDT, Aldrin, Chlordan

H
Cl C Cl DDT: 4
[1,1,1-trichloro-2,2-
CCl3
bis(p-chlorophenyl)ethane]
e) Herbicides: Kills broad leaf weeds but allow narrow leaf plants to
grow unharmed and in greater yield

Cl Cl

OCH2CO2H

2,4-D
2,4-dichlorophenoxyacetic acid

5
 Carbon-Halogen Bond Lengths, Bond Strength and Dipole Moment

Bond Strength Dipole Moment

Bond Bond Length (Å)
(Kcal/mol) (D)

CH3–F 1.39 109 1.82

CH3–Cl 1.78 84 1.94

CH3–Br 1.93 70 1.79

CH3–I 2.14 56 1.64

The size of the halogen atom increases going down the periodic table  the C–X bond
length increases going down the periodic table.

6
 Physical Properties of Organic Halides

Flouride Chloride Bromide Iodide

Group bp (°C) Density (g mL–1) bp (°C) Density (g mL–1) bp (°C) Density (g mL–1) bp (°C) Density (g mL–1)

Methyl –78.4 0.84–60 –23.8 0.9220 3.6 1.730 42.5 2.2820

Ethyl –37.7 0.7220 13.1 0.9115 38.4 1.4620 72 1.9520

Propyl –2.5 0.78–3 46.6 0.8920 70.8 1.3520 102 1.7420

Butyl 32 0.7820 78.4 0.8920 101 1.2720 130 1.6120

CH2=CH– –72 0.6826 –13.9 0.9120 16 1.5214 56 2.0420

CH2=CHCH2 –3 45 0.9420 70 1.4020 102-103 1.8422

C6H5– 85 1.0220 132 1.1020 155 1.5220 189 1.8220

C6H5CH2– 140 1.0225 179 1.1025 201 1.4422 93 10 1.7325

7
 Solubilities:
 Many alkyl and aryl halides have very low solubilities in water, but they
are miscible with each other and with other relatively nonpolar solvents.
 Dichloromethane (CH2Cl2, methylene chloride), trichloromethane (CHCl3,
chloroform), and tetrachloromethane (CCl4, carbon tetrachloride) are
often used as solvents for nonpolar and moderately polar compounds.

8
 Boiling points:
 Methyl iodide (bp 42 °C) is the only monohalomethane that is a liquid at room

temperature and 1 atm pressure.

 Ethyl bromide (bp 38 °C) and ethyl iodide (bp 72 °C) are both liquids, but ethyl

chloride (bp 13 °C) is a gas.

 The propyl chlorides, propyl bromides, and propyl iodides are all liquids.

 In general, higher alkyl chlorides, bromides, and iodides are all liquids and tend to

have boiling points near those of alkanes of similar molecular weights.

 Polyfluoroalkanes tend to have unusually low boiling points.

 Hexafluoroethane boils at –79 °C, even though its molecular weight (MW = 138) is 9

near that of decane (MW = 144; bp 174 °C).

 Polarity of C–X bond:

+ 
C > X

• The carbon-halogen bond of alkyl halides is polarized.

• The carbon atom bears a partial positive charge, the halogen
atom a partial negative charge.
• They exhibit dipole-dipole interactions because of their polar
C—X bond, but because the rest of the molecule contains only
C—C and C—H bonds, they are incapable of intermolecular 10
hydrogen bonding.
• The electronegative halogen atom in alkyl halides creates a polar C—
X bond, making the carbon atom electron deficient. Electrostatic
potential maps of four simple alkyl halides illustrate this point.

Electrostatic potential maps of

four halomethanes (CH3X)

11
NOMENCLATURE OF ALKYL HALIDES
Halogen atoms are classified on the basis of the carbon atom to which they
are attached as may be primary 1o, secondary 2o or tertiary 3o exactly as the
hydrogen atom:

1o Hydrogen atoms

CH3
H 3C CH CH2 CH3
3o Hydrogen atom 2o Hydrogen atoms

1- Haloalkanes:

1. Find longest chain, name it as parent chain (Contains double or

triple bond if present) 12
2. Number from end nearest any substituent (alkyl or halogen)
 CH3CH2Cl CH3CH2CH2F CH3CHBrCH3
IUPAC name Chloroethane 1-Fluoropropane 2-Bromopropane

Common name Ethyl chloride n-Propyl fluoride Isopropyl

bromide
Class of 1o 1o 2o
carbon

When the parent chain has both a halo and an alkyl substituent attached to
it, number the chain from the end nearer the first substituent.

CH3 CH3

CH3CHCHCH2CH3 CH3CHCH2CHCH3

Cl Cl
13
2-Chloro-3-methylpentane 2-Chloro-methylpentane
 Common names for simple haloalkanes are accepted by the IUPAC 
alkyl halides (radicofunctional nomenclature).

(CH3)3CBr CH3CH(CH3)CH2Cl (CH3)3CCH2Br

2-Bromo- 1-Chloro-2-methylpropane 1-Bromo2,2dimethylpropane

2methylpropane

tert-Butyl bromide Isobutyl chloride Neopentyl bromide

14
 CH3
CH2CH3

Cl

4-Chloro-2-ethyl-1-methylcyclohexane
(not 1-Chloro-3-ethyl4methylcyclohexane)

Br

1-Bromo-3-ethyl-2-methylcyclopentane 15
not 1-bromo-2-methyl-3-ethylcyclopentane
Preparation of Organic Halogen Compounds
Chloro, Bromo, and Iodo Compounds
Direct halogenation of hydrocarbons.
a) Halogenation of alkanes: Alkyl halides

RH + X2 uv or heat RX + HX (X = Cl, Br)

b) Halogenation of alkenes: Allyl halides

H2C CHCH2R + X2 uv or heat H2C CHCHXR + HX

c) Halogenation of alkyl benzenes: Benzyl halides

ArCH 2R + X2 uv or heat ArCH 2XR + HX (X = Cl, Br)

d) Halogenation of aromatic ring: Aryl halides 16

FeX3
ArH + X2 ArX + HX (X = Cl, Br)
Halogenation of Alkanes

R-H + X2 R-X + H-X

Reactivity: F2 >> Cl2 > Br2 >> I2

Chlorination of Methane

Mechanism of free radical halogenation has three distinct steps

1. Initiation
2. Propagation
3. Termination
17
Free radical chlorination is not very useful for making alkyl
chlorides: polychlorination, non-specific chlorination
 CH3 CH2Br

Br2
+ HBr
UV light

Toluene Benzyl bromide

CH2CH3 CHClCH3 CH2CH2Cl

Cl2
UV light +

Ethylbenzene 1-Chloro-1-phenylethane 1-Chloro-2-phenylethane

(major product) (minor product)

CH3 CH3 CH3

Br2 Br
+
FeBr 3
18
Br
 Addition of HX to unsaturated hydrocarbons

a) Addition of HX to alkenes: Alkyl halides

C C + HX C C (X = Cl, Br)

H X
b) Addition of HX to alkynes: Vinyl halides
H
C C + HX C C (X = Cl, Br, I)
X

Conversion of alcohols: Alkyl halides

heat
ROH + HX (or PX 3 or SOX2) RX (X = Cl, Br, I)
19
Reaction of Primary Alcohols with Hydrogen Halides:
The SN2 Mechanism:

Methyl and primary carbocations are the least stable, and they are
not likely to be intermediates in reaction mechanism

RH2C-OH + H-X RH2C-X + HOH

Reactivity of the alcohol:

H H H R
H C OH << R C OH < R C OH < R C OH
H H R R
Methyl Primary (1°) Secondary (2°) Tertiary (3°)

increasing reactivity

Reactivity of the H-X : parallels the acidity of HX

20
HF < HCl < HBr < HI
Other Methods for Converting Alcohols to Alkyl Halides
Preparation of alkyl chlorides by the treatment of alcohols
with thionyl chloride (SOCl2)

R-OH + SOCl2 + base R-Cl + SO2 + HCl

Preparation of alkyl bromides by the treatment of alcohols

with phosphorous tribromide (PBr3)

R-OH + PBr3 R-Br + P(OH)3

These methods work best on primary and secondary alcohols. 21

They do not work at all for tertiary alcohols
 Halogen Exchange: A Way to Alkyl Fluorides

 An alkyl chloride or bromide is heated in the presence of a

metallic fluoride such as AgF, Hg2F2, or SbF3.

CH3Br + AgF heat

CH3F + AgBr

 The manufacture of chlorofluoro compounds, known as

Freons.

The simplest Freon, CC12F2, is made as follows.

heat
3CCl4 + 2SbF3 3CCl2F2 + 2SbCl3 22
Chemical Properties of Organic Halogen Compounds
There are three main classes of reactions for the organic halogen

compounds; these are :

Nucleophilic Substitution,

Elimination reaction

and

Organometallic formation.

23
Nucleophilic Substitution Reactions:
The electron _deficient carbon atom in alkyl halides renders
these compounds susceptible to reaction with electron –rich
reagents:

Nu  + R X R Nu + X
Nucleophile Alkyl halide Product Halide ion
(substrate)

A nucleophile, is a species with an unshared electron pair (lone-pair

electrons), reacts with an alkyl halide (substrate) by replacing the
halogen substituent (leaving group).

+ 
This is the postive center The electronegative halogen
C > X 24
that the nuceophile seeks. polarizes the CX bond.
25
Examples:

HO  + CH3 Cl CH3 OH + Cl 

CH3O  + CH3CH2 Br CH3CH2 OCH3 + Br 


I + CH3CH2CH2 Cl CH3CH2CH2 I + Cl 

Nucleophilic Reagents
Being electron –pair donor, nucleophilic reagents must necessarily
possess unshared electrons, they include:
Negative ions
e.g. HO Hydroxide ion, HS Hydrosulphide ion, RO Alkoxide ions,

N C Cyanide ion, X Halide ions, ...etc.

Neutral molecules
26
e.g. H2O , R O H, R O R , H3N , R3N , ...etc.
Nucleophiles and bases are structurally similar: both have a lone pair or a 
bond. They differ in what they attack.

• Although nucleophilicity and basicity are interrelated, they are

fundamentally different.
Basicity is a measure of how readily an atom donates its electron pair to a proton
at the moment of nucleophilic substitution. It is characterized by an equilibrium
constant, Ka in an acid-base reaction, making it a thermodynamic property.
Nucleophilicity is a measure of how readily an atom donates its electron pair to
27
other atoms. It is characterized by a rate constant, k, making it a kinetic property.
Nucleophilicity depends on the ability of the nucleophile to donate a
pair of electrons to H+ (basicity) and on the influence on such ability
from the substrate(usually polarizability).
Polarizability is characteristic for large atoms and greatly increases

nucleophilicity.

- - - - -
HO H2O I Br Cl F

Basicity Basicity

Nucleophilicity Nucleophilicity

Weaker bases make better leaving groups. 28

The Leaving Group
In a nucleophilic substitution reaction of R—X, the C—X bond is
heterolytically cleaved, and the leaving group departs with the electron
pair in that bond, forming X:¯. The more stable the leaving group X:¯, the
better able it is to accept an electron pair.

• For example, H2O is a better leaving group than HO¯ because H2O is a
weaker base. 29
• There are periodic trends in leaving group ability:

30
 Good leaving group for nucleophilic susbstitution

Starting material Leaving group Conjugate acid pka

R-Cl Cl- H-Cl -7

R-Br Br- H-Br -9

R-I I- H-I -10

R-OH2+ H2O H3+O -1.7

Molecules under undergo Good leaving

nucleophilic substitution group

31
 Poor leaving group for nucleophilic susbstitution

Starting material Leaving group Conjugate acid pka

R-F F- H-F 3.2

R-OH -OH H2O 15.7

R-NH2 -NH NH3 38

2

R-H H H2 35

R-R R- R-H 50

Molecules do not under Poor leaving group

undergo nucleophilic
substitution
32
The Leaving Group
• Stable anions that are weak bases are usually
excellent leaving groups and can delocalize charge

33
 Poor Leaving Groups

• If a group is very basic or very small, it is prevents

reaction

34
 Nucleophilic substitution (SN) Reactions
Nucleophile Substitution product
OH Alcohol
R OH
R'O Ether
R OR'
SH
R SH Thiol
R'S Thioether
R SR'
 X CN
R X R C N Nitrile
(R=Me, 1o, or 2o) R' C C
R C C R' Alkyne
(X=Cl, Br, or I) O O
R'CO Ester
R OCR'
NR'3
R NR'3X Quaternary ammonium halide
N3
R N3 Alkyl azide 35
R Br I  
R I (+ Cl or Br )
R Cl
 Reaction kinetics

• The study of rates of reactions is called kinetics

• Rates decrease as concentrations decrease but the rate
constant does not
• The rate law depends on the mechanism
• The order of a reaction is sum of the exponents of the
concentrations in the rate law – the example below is second
order

Experiments show that for the reaction

OH- + CH3Br  CH3OH + Br-

Rate = k[OH-][CH3Br] 36
• Rate is change in concentration with time
• Depends on concentration(s), temperature, inherent
nature of reaction (activation energy)
• A rate law describes relationship between the
concentration of reactants and rate of conversion to
products – determined by experiment.
• A rate constant (k) is the proportionality factor
between concentration and rate

Example: for S  P
an experiment might find
Rate = k [S] (first order)
37
 MECHANISM FOR THE SN2 REACTION:
The nucleophile attacks the carbon bearing the leaving group from the back
side.
 The orbital that contains the electron pair of the nucleophile begins to
overlap with an empty (antibonding) orbital of the carbon bearing the
leaving group.
 The bond between the nucleophile and the carbon atom is forming, and the
bond between the carbon atom and the leaving group is breaking.
 The formation of the bond between the nucleophile and the carbon atom
provides most of the energy necessary to break the bond between the
carbon atom and the leaving group.

Antibonding orbital

Nu C L Nu 
C + L
Bonding orbital

Stereochemistry of SN2 38
The configuration of the carbon atom becomes inverted during SN2 reaction
 In a nucleophilic substitution:

Bond making and bond breaking occur at the same time.

The mechanism is comprised of one step. In such a bimolecular

reaction, the rate depends upon the concentration of both
39
reactants, that is, the rate equation is second order.
 Stereochemistry of SN2 Reaction
• All SN2 reactions proceed with backside attack of the nucleophile,
resulting in inversion of configuration at a stereogenic center.

40
One-Step Mechanism: SN2 Reactions

Summary;
1. The SN2 reaction is a single, concerted process.

2. The rate of SN2 reaction depends on the concentrations

of both the alkyl halide and the nucleophile.

3. The reaction is fastest for primary halides and slowest

for tertiary halides.
4. All SN2 reactions proceed with complete inversion of
configuration.
41
 Characteristics of the SN2 Mechanism

Characteristic Result

Kinetics • Second-order kinetics, rate = k[RX] [:Nu-]

Mechanism • One step

Stereochemistry • Backside attack of the nucleophile

• Inversion of configuration at a stereogenic center

Identity of R • Unhindered halides react fastes

• Rate: CH3X > RCH2X > R2CHX > R3CX

42
• Methyl and 1° alkyl halides undergo SN2 reactions with ease.
• 2° Alkyl halides react more slowly.
• 3° Alkyl halides do not undergo SN2 reactions. This order of reactivity can
be explained by steric effects. Steric hindrance caused by bulky R groups
makes nucleophilic attack from the backside more difficult, slowing the
reaction rate.
43
Electrostatic potential maps illustrate the effects of steric hindrance
around the carbon bearing the leaving group in a series of alkyl halides.

Steric effects in the SN2 reaction

44
Two-Step Mechanism: SN1 Reactions

SN1 reactions take place with both inversion and retention of

configuration.

A mechanism that accounts for these facts involves two steps.

Step 1. The tertiary alkyl halide ionizes to form a carbocation.

This is the slow, rate-determining step.
CH3
H3C
Slow + X (X = Cl, Br, I)
C X C
H3C rate-determining
step H3C CH3
H3C
t-Butyl halide
45
Step 2. A covalent bond forms between the carbocation and the
OH- nucleophile.

This step occurs rapidly.

The nucleophile has as much chance to bond with the

positively charged carbon on the same side as the departed
leaving group (giving retention of configuration) as on the back
side (leading to inversion).

If the starting alkyl halide were optically active, the product

would be a racemic mixture. 46
 Mechanisms of Nucleophilic Substitution:

• The rate of an SN1 reaction is affected by the type of alkyl halide

involved.

• This trend is exactly opposite to that observed in SN2 reactions. 47

 Reaction:

acetone
(CH3)3CCl + 2 H2O (CH3)3COH + H3O+ + Cl

Mechanism of SN1

Step 1

CH3 CH3
slow 
CH3 C Cl H3C C + + Cl
H2O
CH3 CH3
Aided by the polar solvent This slow step produces the relatively stable
a chlorine departs with 3o carbocation and a chloride ion. Although
the electron pair that not shown here, the ions are slovated (and
bonded it to the carbon. stabilized) by water molecules.

48
 Step 2
CH3 CH3
fast
H3C C + + O H H3C C O+ H
CH3 H CH3 H
A water molecule acting as a Lewis The product is a
base donates an electron pair to the tert-butyloxonium
carbocation (a Lewis acid). This gives ion (or protonated
the cationic carbon eight electrons. tert-butyl alcohol).

Step 3

CH3 CH3
+
fast +
H3C C O H + O H H3C C O H + H O H
CH3 H H CH3 H
A water molecule acting as a The products are tert-butyl
Bronsted
/ base accepts a proton alcohol and a hydronium ion.
from the tert-butyloxonium ion. 49
 Carbocation formation and stability
• Key features of the SN1 mechanism are that it has two steps, and
carbocations are formed as reactive intermediates

• The effect of the type of alkyl halide on SN1 reaction rates can be explained by
considering carbocation stability.
• Carbocations are classified as primary (1°), secondary (2°), or tertiary (3°),
based on the number of R groups bonded to the charged carbon atom. As the
number of R groups increases, carbocation stability increases.

Alkyl groups are electron donating groups that stabilize a positive charge. 50
The relative stabilities of carbocations is 3° > 2° > 1° > methyl
THE STEREOCHEMISTRY OF SN1
REACTIONS
The carbocation has a trigonal planar structure  It may react with
a nucleophile from either the front side or the back side so that a
racemic mixture is obtained :

Same product

CH3 CH 3 H3C
+ back side front side +
H2O C H 2O C + H 2O C OH2
CH3 attack attack H3 C
CH3 H3C CH H3C
3

Racemic mixture : is two equal parts of oppositely optically active

compounds
51
 This side open to This side shielded
attack from attack
Br 
D BD BD
B H2O
Br 
+ +
C Br H2O C H2O C H2O
A A A
Ion pair Free carbocation

D D D
B B B
HO C HO C + C OH
A A A
Inversion Racemization

52
Factors Favoring SN1 versus SN2 Reactions

Factor SN1 SN2

3° (requires formation of a relatively Methyl > 1° > 2° (requires
Substrate
stable carbocation) unhindered substrate)
Strong Lewis base, rate
Weak Lewis base, neutral molecule,
favored by high
Nucleophile nucleophile may be the solvent
concentration of
(solvolysis)
nucleophile
Polar aprotic (e.g. DMF,
Solvent Polar protic (e.g. alcohols, water)
DMSO)
Good LG important to form C+ Not as important but
Leaving group
enhances reaction

Kinetics: rate = k[RX] rate = k[RX][Nu:]

both inversion and retention

Stereochemistry inversion only
(racemic)
rearrangements not
Rearrangement rearrangements common 53
possible