Nucleophilic Substitution

Pre Lab Assignment: Complete the pre-lab cover page and develop a procedure. Draw the
mechanism of the reaction you will complete in lab. Use the proper arrow drawing convention
to show all bond making and bond breaking steps in the reaction.
Learning Goals:
Understand nucleophilic substitution reactions
Introduction:
A substitution reaction takes place when a nucleophile (Nu:) forms a bond with a carbon atom,
displacing a leaving group (L).
H

Nu

Nu

H
H

Sn2
Leaving groups are typically weak Bronsted bases that are stable as anions (often halide anions).
The precise timing of when the leaving group leaves depends on the structure of the substrate
the molecule bearing the leaving group. Methyl and primary alkyl halides tend to undergo SN2
type reactions. In this type of reaction, the nucleophile attacks the carbon from the side opposite
the leaving group and the nucleophile-carbon bond is made simultaneous with the carbon-leaving
group bond breaking. SN2 reactions are one-step and there is an inversion of stereochemistry at
Mechanism for Sn2
Me

HO

Me
HO

Et
H

Me

Br

Br

Et
HO

Br
Et

Sn2 Transition State

Note: Inversion of
stereochemistry

the carbon bonded to the nucleophile.

See also:
(Brown & Poon: Pages 175-176 and http://www.bluffton.edu/~bergerd/classes/CEM221/sne/SN2-1.html)
Additional notes to augment chapter 7, in the handouts section of the course website.
Sn1
If the carbon undergoing substitution is sterically hindered (as is the case with tertiary alkyl
systems) or the intermediate carbocation is relatively stable (tertiary alkyl or resonance stabilized
systems), SN1 reactions are prevalent. In this case, the nucleophile cannot approach the carbon

bearing the leaving group as it would in an SN2 reaction or the carbocation is fairly stable, and
the leaving group leaves first, forming a planar carbocation with a formal positive charge on the
carbon. Once the carbocation is formed, it is attacked by the nucleophile forming a new bond.
Reactivity, in terms of SN1 substitutions, is based on the stability of the carbocation intermediate
formed. SN1 reactions are two step reactions where the first step involves the formation of the
carbocation and the second step involves the attack of the nucleophile. Because of the achiral
nature of the carbocation intermediate, if the carbon bearing the leaving group is chiral, then

stereochemistry is lost in an SN1 reaction. (Brown & Poon: Page 177.)

The reaction you will be carrying out in lab will convert 9-fluorenol to 9-methoxy fluorene using
a nucleophilic substitution reaction.

OH
OCH 3

H 2SO 4
MeOH

Procedure:
Obtain a hotplate, 10 mL round-bottom flask, and heat transfer block from the stockroom. Set
up a reflux apparatus using a 10 mL round-bottom flask and a water condenser (which can be
found in the red kit on your bench).
Before attaching the round bottom flask, add your spin bar and 200 mg of 9fluorenol (pre-weighed) to this flask and place it in your cork ring for safe
holding. Measure out approximately 6 mL of methanol into your graduated
cylinder. In the hood, slowly add 1.5 mL of concentrated sulfuric acid to the
methanol with a transfer pipette (CAUTION: concentrated sulfuric acid is a
strong acid. In case of contact with ANY organic material, immediately
wash with cold water. Do not leave drops of sulfuric acid on the table.
Dispose of the transfer pipette in the container in the back of the hood.). The
solution will become hot as the sulfuric acid is added (Why?). Return to

your bench and pour the H2SO4/MeOH mixture into your flask and reassemble your reflux
apparatus. Rinse the graduated cylinder with cold water. Start circulating the water in the water
condenser. The water flow should be a slow steady stream and should enter from the bottom of
the condenser (as shown in the picture above).
Set the reaction flask in the largest hole in the aluminum block and set the thermometer in the
smallest hole of the aluminum block using the thermometer clamp. Heat the reaction mixture to
about 100C while stirring. The solution should boil gently. Heat the solution for a total of 20
minutes, beginning from the time the reaction flask is put on heat. Remove the reaction flask
from heat, i.e. unplug and move your hot plate, and allow it to cool to approximately room
temperature, but do not detach the flask from the condenser yet. Be careful not to shake the flask
when removing it from the heating block because it may start to boil violently.
During this time obtain two spotting pipettes. Put a small amount of 9-fluorenol in a disposable
culture tube and add enough dichloromethane to dissolve the sample.
Once your reaction has cooled, prepare a TLC plate and spot it with 9-fluorenol and your
reaction mixture. Develop the TLC plate in methylene chloride. Visualize your plate using UV
light and trace around the spots. Pour your reaction mixture into the waste bottle provided in the
hood.
Post Lab:
Include what is required in the Lab Expectations handout.
Tape a properly labeled TLC plate to the observations section of your lab report, and
describe what it illustrates.
Answer the following questions separate from your conclusions.
1. Is this reaction more likely to proceed via an SN1 or SN2 reaction? Explain.
2. Did the reaction favor products or reactants? How can you tell?
3. Whyisconcentratedsulfuricacidusedinthisreactionandnotaqueousacid?
Hint:Whatisthebigdifferencebetweenconcentratedandaqueousacids,and
whatrolewouldthatdifferenceplayinthereaction?(Explainanddrawthe
reactionandshowtheequilibriumthatisdependentontheacid.)
4. Why is Benzyl Bromide, which appears to be a primary halide, able to undergo SN2
and SN1 reactions? Support your answer with drawings.