What is this characterization?

Organic Chemistry II Lab Project
Spring 2004
Prof. R. Kennedy

This semester you will be investigating the reaction of salicylic acid with acetic anhydride to make aspirin. You
will submit one formal report at the end of the semester that details your investigation. I have broken the
project up into several sub-investigations, some of which are done outside lab. I have also scheduled these sub-
investigations through the semester so that I may keep track of your progress. For each sub-investigation you
are to submit a short summary of the results. The other purpose of the schedule is to help us make sure you
have the material you need when you need it. *For all experiments, you must submit a written procedure with
a chemical list and equipment list one week prior to conducting the experiment. Make sure you detail your
equipment list. (Beaker is insufficient, the size you need is required. Thermometer is insufficient, the
temperature range (or at least the maximum temperature) is required.)

The first part of the investigation involves researching the reaction, and modeling the reaction on the computer,
(using Spartan, Alchemy or similar modeling software). Information you will need includes uses and general
information about aspirin and salicylic acid, the mechanism of the reaction under acidic and basic conditions,
the Kas of the acidic hydrogens on salicylic acid and aspirin, physical properties of reactants and products,
solubilities in various solvents of both reactants and products, IR, NMR, UV-Vis and Mass Spectra of both
aspirin and salicylic acid. You will also need to estimate or find the H° of the reaction and estimate the
equilibrium constant at 20°C and 90°C, (assume that G° H°).

The second part* of the investigation involves running the reaction in microscale. You are to design your own
procedure. In this part you will use sulfuric acid as the catalyst. You are to design your procedure to give a
theoretical yield of 1.0 millimole aspirin. I suggest using a 5-fold excess of the acetic anhydride. Almost every
Organic Chemistry lab manual, and many Freshman Chemistry lab manuals, contains an experiment on the
synthesis of aspirin. There are also many examples on the web you can adapt. It is suggested that you find a
way to control the temperature. You are to purify your solid product by recrystallization. Report your
percentage yield on both the crude and purified product. You are to characterize both your crude and purified
product by melting point. You must run your preparation three times to evaluate the reproducibility of your
results.

The third part* of the investigation is to adjust your procedure to produce a theoretical yield of 0.050 moles of
aspirin. You should characterize your crude and purified products by melting point and demonstrate the purity
of your product by TLC. You will be required to submit samples of your purified product for spectroscopic
analysis.

The forth part* of the investigation involves characterizing your product both chemically. The chemical
characterization should include hot and cold solubility tests in various solvents (based on your research as to
what aspirin is soluble in, and including aqueous solubilities at pH 2, 4, 7, 9, 12), and the litmus test. You
should hydrolyze a small amount of your product under acidic conditions and perform the ferric chloride test on
both the hydrolyzed and unhydrolyzed product, (it complexes with the OH group on salicylic acid). You should
also prepare the amide derivative of the product and characterize it by melting point.

The last part* of the investigation involves evaluating the effect of various catalysts on your results. You are to
compare the following catalysts ­ sodium acetate, sulfuric acid, phosphoric acid, pyridine (a base), boron
trifluoride (complexed with ether), (BF3 is a Lewis acid and will bond to the O just like H+1). Since the reaction
is exothermic, the best way to evaluate the effectiveness of the catalyst is to measure the time required for a
certain rise in temperature. Use about 0.1 gram of salicylic acid for each reaction and pick an amount of
catalyst that is convenient and consistent for all catalysts.



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Project Schedule
A. Week 1
1. Find uses of aspirin and salicylic acid and how they act pharmacologically
2. Determine the reactants and products of the reaction
3. Determine the mechanism of the reaction under acidic and basic conditions
4. Determine the melting point, boiling point, density, and solubilities of all reactants and products
in water, alcohol and a nonpolar solvent
5. Determine the Ka of the acidic hydrogen(s) in salicylic acid and aspirin
6. Find spectra, (IR, NMR, Mass Spec, and UV) for salicylic acid and aspirin
B. Week 2
1. Construct computer models of all reactants and products.
2. Minimize the energy of each model using a molecular mechanics program
a) like Spartan energy minimization
3. Determine the Hf of each reactant and product in kJ/mol
a) 1 kcal = 4.2 kJ
4. Use the Hf information from #3 to estimate the Hreaction.
5. Assuming GH, estimate the Kc of the reaction to the nearest whole number exponent on 10
for 20°C and 90°C
a) Kc = e-G/RT, where R = 8.3 J/mol
C. Week 3
1. Research a procedure for the microscale reaction.
2. Submit a written procedure on Thursday, 2/5/04 that includes:
a) chemicals and amounts to be used for 3 runs
(i) reactants to theoretically produce 0.5 millimoles of ASA using salicylic acid as
the limiting reagent and a 0.1 millimoles excess of acetic anhydride
(ii) solvent for the reaction
(iii) solvent for recrystallization of 1 run
b) equipment for 3 runs
(i) running the reaction
(ii) recrystallizing one product
(iii) characterizing crude and purified product by melting point
(a) include known samples of ASA and SA to run parallel for comparision
and standardizing the thermometer
c) what temperature or temperature range the reaction is to be run at
d) how you will know when the reaction is finished
(i) visually or by time




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