Nucleophilic Substitution
Synthesis of 1-Iodobutane
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Nucleophilic Substitution of Alkyl Halides:
Synthesis of 1-Iodobutane
O
Br
C4H9Br
MW 137.02
d 1.28 g/mL
BP 100-104oC
+
NaI
MW 149.89
I
C4H9I
MW 184.02
d 1.62 g/mL
BP 130-131oC
+
NaBr
MW 102.89
sodium bromide is
insoluble in acetone
1-Bromobutane is a primary alkyl halide (not sterically hindered).
Acetone is a polar aprotic solvent. It poorly solvates the iodide nucleophile,
promoting the SN2 mechanism.
Despite having an unfavourable equilibrium (the products are less stable than the
starting materials), the reaction still proceeds essentially to completion. Why is
this?
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Reaction Work-Up
Filter the reaction mixture to remove the precipitated sodium bromide.
Wash with water to remove remaining traces of sodium iodide. The
primary purpose, however, is to remove the bulk of the acetone
solvent from the reaction mixture. The lower layer is the organic layer
(containing our product).
Wash with aqueous sodium bisulfite (NaHSO3) to remove any colouration
due to a small amount of iodine that is often formed as a by-product in
reactions of this type:
I2 + HSO3– + 3 H2O → 2I – + HSO4 – + 2 H3O+
Dry the organic product by standing over sodium sulfate (Na2SO4).
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Product Purification
The 1-iodobutane product is purified by distillation.
Before performing the distillation, you should pre-calculate the expected
boiling point of the 1-iodobutane product:
B.P.760mmHg = B.P.observed – 0.05×(A.P.mmHg – 760)
You know the literature
boiling point (for 760 mmHg)
You know the current
atmospheric pressure
You can thus predict the boiling point
in today’s lab (at the current atmospheric pressure)
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Qualitative Tests
Perform these test-tube tests once reflux is underway!
NaI in Acetone – test for SN2 reactivity
• Iodide ion (I–) is a good nucleophile and a poor base.
• Acetone is a polar aprotic solvent.
• A positive result is indicated by formation of a white precipitate, since NaBr
and NaCl are insoluble in acetone.
AgNO3 in Ethanol – test for SN1 reactivity
• Nitrate ion (NO3–) is a poor nucleophile and a poor base.
• Ethanol is a polar protic solvent.
• Silver ion (Ag+) promotes cation formation (and thus SN1 reactivity):
R X
Ag
R
X
Ag
R
+ AgX
• A positive result is indicated by formation of AgX precipitate
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Qualitative Tests
Substrate structure is very important in determining the mechanism of
reactivity. You’ll test a range of substrate structural types.
Cl
Cl
Cl
Br
1-bromobutane
1-chlorobutane
1o
Cl
Cl
2-chlorobutane
2-chloro-2methylpropane
benzyl chloride
2o
3o
benzylic
chlorobenzene
aryl
Note that the only difference between 1-bromobutane and 1-chlorobutane is
the identity of the leaving group. We can compare these two substrates to
determine whether bromide or chloride is a better leaving group.
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Qualitative Tests
Note that the only difference between 1-bromobutane and 1-chlorobutane is
the identity of the leaving group. We can compare these two substrates to
determine whether bromide or chloride is a better leaving group.
Cl
Br
1-bromobutane
1-chlorobutane
1o
The observed reactivity (SN1 and SN2) sequence for halides is:
R I
>
R Br
>
R Cl
>
R F
C-X bond strength as well as the stability of the X– ion control this order.
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Qualitative Tests
Owing to steric effects, the order of reactivity in SN2 chemistry is:
H3C X
>
H
R C X
H
>
R
R C X
H
>
R
R C X
R
X
X
~
~
aryl and vinyl substrates do
not readily undergo substitution
In SN1 chemistry, the order of reactivity reflects the ease of cation
formation:
R
R C X
R
>
R
R C X
H
~
X
>
H
R C X
H
X
X
>
H3C X
~
~
aryl and vinyl substrates do
not readily undergo substitution
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Tips and Reminders
• Today’s experiment will be conducted in pairs
• Note that most alkyl halides, particularly iodides, are very toxic and are
cancer suspect agents
• During the work-up procedure, the precipitate may be washed with an
additional (small) quantity of fresh acetone in order to maximize the percent
yield
• During liquid-liquid extraction, the lower layer is the organic layer
(halogenated compounds are almost always more dense than water)
• Before performing the distillation, pre-calculate the expected boiling point
• Atmospheric pressure today:
• Don’t forget that a lab report is required for this experiment!
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