4.3 Alkyhalide Preparation

Organohalides synthesis from
alcohol
Reaction of Alcohols with Hydrogen Halides
Reaction type: Nucleophilic Substitution (SN1 or SN2)
Summary
 When treated with HBr or HCl alcohols typically undergo a nucleophilic
substitution reaction to generate an alkyl halide and water.
 Hydrogen halide reactivity order : HI > HBr > HCl > HF (paralleling acidity order).
o Cl ion is a weak nucleophile than Br and I ions b/c HCl bond is stronger than
HBr.
o However, the rxn of ROH with HCl can be enhanced if we use ZnCl2 as a
catalyst.
 Alcohol relative reactivity order : 3o > 2o > 1o > methyl.
 Reaction usually proceeds via an SN1 mechanism which proceeds via a
carbocation intermediate, that can also undergo rearrangement.
 Methanol and primary alcohols will proceed via an SN2 mechanism since these
have highly unfavourable carbocations.
 The reaction of alcohols with HCl in the presence of ZnCl2 (catalyst) forms the
basis of the Lucas test for alcohols.
Reaction type: Nucleophilic Substitution (SN1 or SN2)
Case #1: Reaction of primarily alcohol with HX
SN2 MECHANISM FOR REACTION OF ALCOHOLS WITH HX
Step 1:
An acid/base reaction. Protonation of the alcoholic oxygen to make a better
leaving group. This step is very fast and reversible. The lone pairs on the
oxygen make it a Lewis base.

Step 2:
Attack of the nucleophilic halide ion on the backside electrophilic carbon
via SN2 mechanism, with a simultaneous cleavage of C-O bond and the
loss of the good leaving group, a neutral water molecule, to give alkyl
halide.
o Note: OH and NH are bad leaving groups
Case #2: Reaction of tertiary alcohol with HX
SN1 Mechanism for reaction of tertiary alcohols with HBr

Step 1:
An acid/base reaction. Protonation of the alcoholic
oxygen to make a better leaving group. This step is
very fast and reversible. The lone pairs on the
oxygen make it a Lewis base.

Step 2:
Cleavage of the C-O bond allows the loss of the
good leaving group, a neutral water molecule, to
give a carbocation intermediate. This is the rate
determining step (bond breaking is endothermic)

Step 3:
Attack of the nucleophilic bromide ion on the
electrophilic carbocation creates the alkyl bromide.
o If the carbocation is chiral, then a racemic
mixture will be formed.
Case #3: Reaction of secondary alcohol with HX
Mechanism for reaction of secondary alcohols with HX
 Secondary alcohols reacts with hydrogen halides via either SN1 or

SN2 mechanism depending on reaction conditions.
Lucas Reagent Formula
 Lucas reagent is basically a solution which is formed by the combination of HCl
and ZnCl2.
Lucas Test
This test is more often used to categorize the different types of alcohols based on
the time taken to form a turbid solution or precipitation using the Lucas Reagent
namely:
 Primary alcohol: Here no visible reaction is observed and the solution remains
colorless e.g. 1-Pentanol
 Secondary alcohol: Here the solution turns turbid or cloudy in 5-20 minutes
with slight heating e.g. 2-Pentanol
 Tertiary alcohol: Here the solution turns turbid or cloudy rapidly with the
formation of two separate layers at room temperature e.g. 2-Methyl-2-
butanol.
Organohalides- preparation from ROH and HX
Reaction of Alcohols with other Halogenating agents (SOCl2,PX3)
Reaction type: Nucleophilic Substitution (usually SN2)
Summary
o Alcohols can also be converted to alkyl chlorides using thionyl chloride,SOCl 2, or
phosphorous trichloride, PCl3.
o Alkyl bromides can be prepared in a similar reaction using PBr3.
o Used mostly for 1o and 2o ROH (i.e. SN2)
o In each case a base is used to "mop-up" the acidic by-product.
 Common bases are triethylamine, Et3N, or pyridine, C5H5N.
 In each case the -OH reacts first as a nucleophile, attacking the electrophilic center of the
halogenating agent.
 A displaced halide ion then completes the substitution displacing the leaving group.
 Note that it is not -OH that leaves, but a much better leaving group.
 The advantage of these reagents is in that the reaction is not under the strongly acidic
conditions like using HCl or HBr.
SN2 MECHANISM FOR REACTION OF ALCOHOLS WITH SOCl2
Step 1:
The oxygen of the alcohol reacts as a
nucleophile on the electrophilic S aotm (look at
the electronegtive groups attached to the S).
Step 2:
The added base removes the proton from the O.

Step 3:
The intermediate collapses to reform the S=O
and a chloride ion is lost as a leaving group.

Step 4:
An SN2 reaction of the chloride ion reacts as a
nucleophile on the electrophilic C from the
alcohol to displace SO2 (the leaving group) and
release another chloride ion while forming the
alkyl chloride
Organohalides- preparation from ROH and PBr3
Organohalides- preparation from SOCl2
Organohalides- preparation from tosylate and alcohol
Cleavage of Ethers by HI or HBr
Cleavage of Ethers by HI or HBr
Reaction type: Nucleophilic Substitution (SN1 or SN2 mechanism)

Summary
o Alkyl ethers are cleaved by the strong acids HI or HBr in a nucleophilic
substitution reaction similar to that of alcohols.
o Protonation of the ethereal oxygen creates a good leaving group, a
neutral alcohol molecule.
o The halide ion, bromide or iodide are both good nucleophiles.
o Depending on the structure of the alkyl groups, the reaction can be
SN1 or SN2 like.
If excess HBr is used, what would the products of the reaction be ?

Ans. Two molecules of alkyl halides since ROH + HBr -> RBr.
Mechanism for Acid Cleavage of Ethers
Case #1 – Primarily Ethers
 Neutral ethers are generally resistant to nucleophiles in substitution
reactions – that’s because the leaving group would have to be RO- ,
which is a very strong base.
 Acid cleavage of primarily ethers via SN2

mechanism
Step 1:
An acid/base reaction. Protonation of the
alcoholic oxygen to make a better leaving group.
This step is very fast and reversible. The lone
pairs on the oxygen make it a Lewis base.
Step 2:
The bromide ion functions as the nucleophile
and attacks via SN2 to displace the good leaving
group, neutral alcohol molecule, by cleaving the
C-O bond. This results in the formation of an
alkyl bromide and an alcohol.
Case #2 – Tertiary Ethers
o Clearly the SN2 is not in play here, as the tertiary carbons are much too
hindered for a backside attack.
o Tertiary ether undergo cleavage via SN1 mechanism
Case #3 – Secondary Ethers
o Cleavage of secondary ethers should follow via either SN1 or SN2
mechanism depending on reaction conditions.
Case #4 – Mixed Ethers

o If you have two different groups attached to the oxygen (“unsymmetrical
ethers”). Which way is it going to break? E.g. t-butyl methyl ether?
 It gives a mixture of products.

4.3 Alkyhalide Preparation

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Organohalides synthesis from

SN2 MECHANISM FOR REACTION OF ALCOHOLS WITH HX

SN1 Mechanism for reaction of tertiary alcohols with HBr

Mechanism for reaction of secondary alcohols with HX

 Secondary alcohols reacts with hydrogen halides via either SN1 or

Reaction type: Nucleophilic Substitution (SN1 or SN2 mechanism)

If excess HBr is used, what would the products of the reaction be ?

 Acid cleavage of primarily ethers via SN2

Case #4 – Mixed Ethers

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