CHEMISTRY 126

STUDY UNIT 8
ALKYL HALIDES
Alkyl halides/Organohalogen compounds

• Rich natural sources of alkyl halides are marine

organisms; otherwise they are mostly synthesised in
the laboratory
• Have the generic formula R-X, where R is an alkyl
group and X= F, Cl, Br, I
• The C-X bond is highly polar, thus Cδ+―Xδ-
• Recall:
– alkyl halides are substitution rxn products of alkanes and
– addition rxn products of alkenes on reaction with HX.

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Alkyl halides/Organohalogen compounds

• The electrophilic nature of the C-atom facilitates

nucleophilic substitution of the X-atom:
R-X + HO- R-OH + X-
• Elimination (i.e. dehydrohalogenation: removal of a
H- and X- atoms) rxns are also possible to give
alkenes
– Definition of Elimination reaction: Elimination involves the
loss of two atoms/groups from the substrate – usually with
formation of a π bond

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Nomenclature and classification
• They are named similar to alkanes where the
halogen is considered to be a substituent.
• May be classified as 1 ,̊ 2 o
̊ r 3 å lkyl halides
depending on whether the halogen is attached
to:

1o 2o 3o

• Like hydrocarbons, they are generally insoluble

in, or immiscible with water
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Grignard reagents
• Alkyl halides are the starting materials for preparing
Grignard reagents
• These compounds are very useful sources of organic
nucleophiles that can be used in nucleophilic
substitution reactions
• To prepare a Grignard reagent, the alkyl halide is
reacted with magnesium (Mg) in diethyl ether (CH3CH2-
OCH2CH3, also represented by the abbreviation Et2O):

M
g
R
-
X R-
M
g
X
E
t
O
2
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 Grignard reagents
• RMgX (the Grignard reagent) is a source of R-, an
organic nucleophile.
• RMgX reacts with a proton (H+) from an acid or
from water to produce the corresponding alkane:

M
g +
H M
gX
R
-
X R
-
MgX R
-
H +
E
t
2O

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 Grignard reagents
Examples:
a) M
g +
H
Mg
C
l
H
C
-
C
3l H
C
-
M
3g
Cl H
C
-
H
3 +2
E
t
O
2

NB: The proton source for protonating the Grignard reagent may be an acid
such as HCl or HBr, but it may also be H2O, as shown in the following
example:
b) H H H

M
g H
O
2
H
C-
CI H
C
3-
CMg
I H
C
3-
CH+Mg
I
(OH
)
3
E
t
2O
C
H3 C
H3 C
H3

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 Nucleophilic Substitution
• Nucleophilic substitution reactions involve the replacement of a
leaving group (LG) with a nucleophile, i.e.

Nu-
-
+ LG-

e.g

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Recall definition of Nucleophiles

• Nucleophiles (Nu) are electron rich (i.e. have lone

pair(s) of electrons) and therefore are attracted to a
positive charge of an e- deficient species, the
electrophile (E).

• Nucleophilicity refers to the ability with which the

nucleophile can make available its e- pair.
• The more available the e-, the more reactive the Nu.
NB: These may also be lone pair e-‘s.
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Nucleophiles
Common nucleophiles include:
Nucleophile Neutral Anionic
Halide I-, Br-, Cl-
Oxygen H2O, ROH OH-, RO-.
Nitrogen NH3, RNH2, R3N NH2-, RNH- .
Sulfur RSH, R2S SH-, RS-
carbon (RMgX) R-, N≡C-,
R-C≡C-
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Leaving Groups
The following table lists some common leaving groups.

Strength Leaving Group

Excellent NH3
Very Good I-, H2O
Good Br-
Fair Cl-
Poor F-
Very poor OH-, RO-, NH2-
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Mechanism of Substitution Reactions
Experimentally if you measure the rate of substitution
for the following reactions you will find the following
rate laws:

OH- Br- rate = k[CH3Br][OH- ]

OH- Br- rate = k[(CH3)3CBr]

Why the difference?

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 Substitution Reactions: SN2
• The first reaction is dependent on the concentrations of both
the substrate and nucleophile, i.e.

OH- Br- rate = k[CH3Br][OH- ]

• This implies it is a bimolecular reaction that occurs in one step.

• There is a single transition state (TS), in which the new bond to
the Nu is forming simultaneously while the old bond to the LG is
breaking, i.e.

+
OH- HO- Br- Br-

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Example:

OH- therefore
OH- strong nucleophile attracted to +
O has unshared pairs of e- on CH3I
and a neg charge

OH- attacks the back

CH3I: substrate as it is side of the C atom. C I is the LG – leaves with
attacked by the reagent
can only have 8 e-, C-I its pair of e- - stable
CH3I is electrophilic (+)
because it is bonded to the
bond begins to break as halide ion
electronegative I (-) atom HO-C bond forms

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 Substitution Reactions: SN2
The reaction coordinate
diagram indicates this
one step mechanism.
• Rate = [substrate] and
[Nu]
• Back-side attack of the
Nu
• Fastest for 1°, slowest
for 3°(due to a crowded
transition state)
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Substitution Reactions: SN1
• The second reaction is dependent only on the concentration
of the substrate, i.e.

OH- Br- rate = k[(CH3)3CBr]

• This implies it is a unimolecular reaction that occurs in more

than one step.
• The reaction involves:
– firstly the loss of the LG to generate an intermediate carbocation;
– carbocation subsequently reacts with the available nucleophile i.e.

- -
OH (CH3)3C OH- Br- (CH3)3C Br
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Substitution Reactions: SN1
The reaction coordinate
diagram indicates this
multi-step mechanism.
• Rate = [substrate]
• Generates an
intermediate
carbocation
• Fastest for 3°, slowest
for 1° (parallels C+
stability)
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Example:

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SN1 vs. SN2: Nature of Substrate
• The substrate itself has an effect on the mechanism
• SN1 requires an intermediate carbocation (relative
stability)
• SN2 requires a backside attack of the nucleophile
(steric crowding effects), i.e.

primary secondary tertiary

SN1 reactivity

SN2 reactivity
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SN1 vs. SN2: Nature of Substrate
• Reactivity of Alkyl bromide to SN1 mechanism:

1 2 43 100,000,000

• Reactivity of Alkyl bromide to SN2 mechanism:

220,000 1350 1 too small to measure

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SN1 vs. SN2: Summary
Summary of SN1 & SN2 reactions:

– 1 ° - reacts via SN2 (can’t make stable carbocation)

– 3 ° - reacts via SN1 (too sterically crowded for SN2)
– 2 ° - reacts via either SN1 or SN2
• Nucleophilic strength and solvent conditions may be
used to control the mechanism if needed.
• Nucleophilic strength:
– SN1: weak nucleophile (e.g. CH3CH2OH; CH3COOH, etc.)
– SN2: strong nucleophile (e.g. NaOMe)
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Elimination Reactions
• A problem arises in nucleophilic substitution
reactions in that nucleophiles are also bases.
• This is especially true for anionic nucleophiles, i.e.
• Nu:- + H+ → Nu:H (Nu-H)

• This can occur by the Nu abstracting a proton (i.e.

acting as a base) from the substrate giving an
elimination reaction.

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 Dehydrohalogenation Reactions
• Dehydrohalogenation is an elimination reaction of
alkyl halides.
• It will compete with a substitution to some degree,
i.e.
LG- substitution

Nu-

-carbon LG- Nu-H elimination

• It is used to produce alkenes or alkynes from alkyl
halides

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 E2 Mechanism
• Regioselectivity: where does the double bond form?
• Zaitsev’s rule: most highly substituted alkene is formed
preferentially
• For geometric isomers: trans > cis
CH3CH2O-

CH3CH2OH

20% 60% 20%

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 Revision:
• Classify each reaction as a substitution, elimination or
neither. Identify the leaving group in each reaction and
the nucleophile in the substitutions.

Na+ -OCH3 + NaBr

H2SO4
+ H3O+ + HSO4-

KI
+ KI + KBr

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 Revision:
• Classify each reaction as a substitution, elimination or neither.
Identify the leaving group in each reaction and the nucleophile in
the substitutions.
LG + - Nucleophile
Na OCH3 + NaBr Subsitution

H2SO4
+ H3O+ + HSO4- Elimination
OH is protonated, H2O is the leaving
group
LG
KI
+ KI + KBr Elimination

LG Iodide ion is a nucleophile that reacts at Br 30