Download Preparation of an Alkyl Halide Nucleophilic Substitution, S

11/30/2012
Preparation of an Alkyl Halide
Conversion of a 3o Alcohol to
3-Chloro-3,7-dimethyloctane
Nucleophilic Substitution, SN
Nu:
+
R
L
SN
R
Nu
+
L:
Substitution of one group for another at an
sp3 hybridized carbon is a very common
method of functional group interconversion.
Nu: represents an atom or group of atoms
that has nucleophic character. The
nucleophile donates its electron pair to form
a new covalent bond to carbon as the
leaving group takes an electron pair with it.
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Nucleophilic Substitution
All good nucleophiles in this reaction possess
a non-bonding pair of electrons. Therefore,
chloride ion, bromide ion, hydroxide ion,
cyanide ion, water, and ammonia are typical
nucleophiles.
NUCLEOPHILES
Cl
C
N
Br
OH
HOH
NH3
Nucleophilic Substitution, SN
Nu:
+
R
L
SN
R
Nu
+
L:
“L” represents the leaving group in this
reaction. Good leaving groups are the
conjugate bases of strong acids. Therefore,
iodide, bromide, and chloride are good
leaving groups. Hydroxide ion is a poor
leaving group, but a neutral water molecule
is a good leaving group.
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Alkyl Halides from Tertiary Alcohols
R
OH
HX
+
R
X
+
H2O
3o
The most valuable method for synthesis of
alkyl halides is synthesis from alcohols.
The simplest method for converting an
alcohol to an alkyl halide involves treating
an alcohol with hydrogen halide. This
reaction works well only with tertiary
alcohols.
Alkyl Halides from Tertiary Alcohols
R
OH
HX
+
R
X
+
H2O
3o
Tertiary alcohols react much more rapidly in
this reaction because the reaction proceeds
through an SN1 reaction mechanism.
Relative Reactivity in SN1 Reactions
R3C
3o
L
>
R2CH
2o
L
>>
RCH2
L
1o
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Mechanism of SN1 Reaction of Alcohols
There are three steps in the mechanism for
reaction of a tertiary alcohol with HCl. The
first step is protonation of the alcohol by the
acid.
1)
CH3
CH3
R
C
OH
+
H
OH2
R
Cl
CH3
C
CH3
OH2
+ H2O
Cl
Mechanism – Second Step
The second step of the reaction involves the
slow, rate-determining loss of a neutral
water molecule to form a tertiary
carbocation. This is the step that accounts
for the easy reaction of tertiary alcohols and
very slow reaction of primary alcohols.
2)
CH3
R
C
CH3
CH3
OH2
R
slow
+ H2O
C
CH3
Cl
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Mechanism – Third Step
The tertiary carbocation now undergoes a
rapid reaction with the chloride ion as
nucleophile to give the alkyl chloride. This
reaction is essentially irreversible because
the alkyl chloride forms a separate nonpolar organic layer.
3)
CH3
R
CH3
C
CH3
fast
R
Cl
C
Cl
CH3
Experimental procedure
Mix 10 mL of conc. hydrochloric acid with
3.8 mL (3.17 g) of 3,7-dimethyl-3-octanol
in a 50-mL Erlenmeyer flask containing a
stir bar.
Stir the mixture at a moderate rate for at
least 20 minutes. From time to time use a
plastic dropper to rinse the sides of the flask
with the aqueous (upper) layer in the flask.
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Work-up and Isolation of Product
Transfer the contents of the flask to a test
tube and allow the layers to separate.
Remove the lower, aqueous layer with a
pipet.
Use the Micro-extraction procedure
discussed on page 70 of the lab manual to
wash the organic layer, the top layer,
sequentially with aqueous sodium chloride,
aqueous sodium bicarbonate, and water.
Work-up and Isolation of Product, Cont.
Transfer the organic layer to a vial
containing calcium chloride to remove
water. Then filter the material through a
Pasteur pipet containing a small plug of
cotton into a weighed vial.
Weigh the vial, cap it tightly, and label it
with your name. Then store it in your
section’s storage drawer until next week.
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Clean-up
Aqueous phases may be disposed of in the
sink.
The first rinse of glassware contaminated
with any organic material should be into the
waste container in the hood.
Safety
Be careful with the concentrated
hydrochloric acid. If it comes in contact
with your skin, wash with large amounts of
water and then sodium bicarbonate solution.
Avoid contact with the silver nitrate
solution. It will produce black stains on
skin. Wash any affected area with soap and
warm water.
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