Experiment 3: Oxidation of Aromatic Side Chains: Synthesis of

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Experiment 3: Oxidation of Aromatic Side Chains: Synthesis of
Dr. Hoeger, Chemistry 233L
Page 1 of 3
Experiment 3: Oxidation of Aromatic Side Chains: Synthesis of Aromatic
Carboxylic Acids
Purpose
To prepare and identify an aromatic carboxylic acid prepared from an unknown starting material by
oxidation of the alkyl side chains present using KMnO4 in basic solution.
Introduction
Side chains of aromatic compounds are susceptible to oxidation by strong oxidizing agents such as
aqueous potassium permanganate (KMnO4) under basic conditions. For example, toluene can be
readily oxidized to benzoic acid according to the following unbalanced equation:
C6 H 5CH 3 + MnO4! " C6 H 5COOH + MnO2
Benzylic oxidation is used in identification of aromatic natural products especially when spectroscopic
techniques are not available. For example, an antibiotic formed from penicillium was identified in 1952
with the help of permanganate oxidation. This method lends itself well to determine substitution
patterns present on aromatic rings. For example, o-, m- and p-xylene will each give a different
dicarboxylic acid upon oxidation:
CH3
COOH
CH3
COOH
Phthalic acid
CH3
COOH
Isophthalic acid
CH3
CH3
CH3
COOH
Terephthalic acid
CH3
COOH
The mechanism of this oxidation, as is the case in many other oxidations, involves radicals; as such,
not all side chains will be susceptible to oxidative cleavage. For example, an acetamido side chain
(—NHCOCH3) will not undergo oxidation while an amino (—NH2) side chain will, converting it into a
nitro group. Halogen substitutents are also impervious to permanganate oxidation. In fact for an alkyl
Dr. Hoeger, Chemistry 233L
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group to undergo oxidation at least one benzylic hydrogen must be present; as a result, a tert-butyl
group will not undergo oxidation.
In this experiment, you will be given a quantity of an unknown aromatic compound that contains side
chains that are oxidizable (and some that may not be…). You will prepare the corresponding
carboxylic acid, isolate and identify it. From that information you will be able to identify your
unknown. Your instructor will provide you with a list of possible unknowns.
Materials needed
• Potassium permanganate
• 3 M NaOH
• Unknown aromatic starting material**
• Concentrated HCl
• Filter aid (Celite)
• Setups for reflux and simple distillation
• Gravity and vacuum filtration setups
Procedure
Obtain your unknown from the instructor. Be sure to note its color, odor and any other physical
characteristics it may exhibit.
Into a 250 mL round bottom flask place 5 g of KMnO4, 100 mL of water, 2-3 pellets of solid
NaOH and ca. 1.6 mL of your unknown (record weight before addition). Add a magnetic stirring bar to
your flask before assembling a reflux apparatus. Dissolve the all the reagents by warming and stirring,
and then GENTLY heat this mixture at reflux for 1.5 hrs. Do not heat rapidly, as the mixture will
bump if you do so. Test the solution for unreacted permanganate in the following way: remove a drop
of the reaction mixture and place it on a piece of clean filter paper. In the center of the drop you
should see a brown spot (this is MnO2); if you see a purple ring around the brown spot you have
permanganate remaining. If permanganate remains, heat the reaction for 30 minutes longer; if it still
gives you a purple ring add small amounts of solid sodium bisulfite to the hot mixture (no more than
ca. 0.5 g at a time); do so until the spot test is negative but DO NOT ADD A LARGE EXCESS! Once
negative, carefully add 2 g of filter-aid (Celite) to the hot mixture and vacuum filter; wash the flask
and the filter cake with two 10 mL portions of hot water. Discard the filter cake and proceed with the
filtrate.‡
If the filtrate is turbid, or seems to have “floaters”, gravity filter it to remove particulates. Cool
the filtrate in an ice bath and acidify by carefully adding concentrated HCl to the filtrate until no more
precipitate forms (this will take 5-10 mL of HCl). Collect the aromatic acid by vacuum filtration.‡
Recrystallize from a minimal amount of hot water. Determine melting point and yield of your product;
from this information determine the identity of your unknown aromatic starting material. Turn your
product into your instructor.
‡
: Indicates convenient stopping points in a 2-3 hour laboratory period
Dr. Hoeger, Chemistry 233L
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General Notes
You should be able to complete this entire experiment in two three-hour laboratory periods or one
five-hour lab. If done in two lab periods, period one should take you through the oxidation and
filtration stage; the second period should allow you to concentrate, isolate and recrystallize your
product. Melting points, IR, NMR, and final weights may be taken in the beginning of the following
lab period if your recrystallized product is not fully dry (your instructor will tell you what to do). If the
filtrate has evaporated between periods 1 and 2 to a volume of less than 30 mL, add water to get to that
volume and proceed.
You should have the following in your laboratory notebook before coming to lab: i) a balanced
chemical equation for the permanganate oxidation of p-xylene; and ii) a mechanism for the oxidation
of toluene using permanganate.
**: Possible unknowns include toluene, o-, m-, or p-xylene, o-, m-, or p-chlorotoluene, pacetamidotoluidine, among others
Questions (to be done on cover sheet provided for this experiment)
1. Assuming that bisulfite is oxidized to sulfate under basic conditions, write a balanced equation for
this process using permanganate as the oxidizing agent (assume MnO2 is formed as well). How
much sodium bisulfite would you have to add if 25% of the original permanganate remained?
What if 10% remained?
2. a) Look up the melting points of the carboxylic acids formed from the oxidation of:
i) p-xylene
ii) m-chlorotoluene
iii) o-chlorotoluene
b) Using C-13 NMR, how can you differentiate between o-, m-, and p-chlorotoluene? How about
using H-1 NMR?
3. Make a list of what would happen (i.e. products you would obtain) if the following functional
groups were present on the aromatic ring (assume the group is directly attached to the aromatic
ring):
i) aldehyde
ii) ketone
iii) —CH2OH
iv) —CH(OH)CH3
v) —OH (i.e. a phenol)
vi) —OCH3 (i.e. an ether)

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