John Lucci

CHM 255

11/26/16

Organic Chemistry I Lab

TA: Meredith Ward

Aspirin Synthesis – Alternate (Non-Microwave) Procedure

Abstract:

The strong electrophilic nature of the Lewis acid acetic anhydride is increased when protonated

by phosphoric acid, enabling formation of a tetrahedral intermediate through attack of the nucleophilic

aqueous salicylic acid, the hydroxyl- group of which is then deprotonated by the reformation of the

phosphoric acid, causing the leaving of the ester group as an acetate ion which is subsequently

reprotonated by the acetylsalicylate ion to form aspirin and acetic acid. Recrystalization was partaken

using water, isolating acetylsalicylic acid due to the polar solubility of the acetate ion. The product of this

reaction was compared to the same batch of salicylic acid from which the reactant came, contrasted by

retention factor as a measurement of stationary phase affinity using Thin-Layer Chromatography (TLC),

melting point as a measure of volatility, and ferric chloride colorimetric test to test for the presence of

phenol groups as a measure of hydroxyl-FeCl3 complex formation. These three tests were successful in

accomplishing the objective of proving the formation of the product, 2-(acetyloxy)benzoic acid, also

known as aspirin and herein referred to as acetylsalicylic acid, but more importantly proved the lack of

completion of the reaction by testing against a standard of salicylic acid, similarities of which were seen

during TLC and FeCl3, indicative of remaining salicylic acid . Overall, these tests proved the reactivity of

salicylic acid to acetic anhydride in an acidic workup, but more so they proved the contrast between a

hydroxyl- and acetyloxy substiution on the 2- position of the benzoic acid ring.
Theoretical Yield: .215 g of salicylic acid *(1/138.12 g/mol SAMM)*180.157 ASAMM=

0.27391377063 mg of 2-(acetyloxy)benzoic acid

Procedure: Refer to Aspirin Synthesis – Alternate (Non-Microwave) Procedure1

Modifications: 0.215 g of salicylic acid

Time for salicylic acid to go into solution: 2 minutes, Total Reaction time: 12 minutes

FeCl3 test was unshaken for ten minutes

Results:

Substance: Retention Factor

(Rf)
Salicylic Acid 0.731
Partner’s 0.154
Unknown
Product
Unknown 0.346
Product
Figure 1. TLC of Salicylic acid (A) partners product
(B) and product (C)
Final Product: 0.3319 grams

Melting point range 141OC to 145OC.

FeCl3 colorimetric results showed brownish-yellow when unshaken, and formed a

gradient going from burgundy to maroon when shaken.
Figure 2. FeCl3 results
(0.3319 mg PY/0.27391377063 mg TY) *100% = 121.16% Yield for Salicylic Acid
(above) and product
(right)

Conclusions:

Overall, the results indicate formation of aspirin in spite of operator error and unpreparedness,

exemplified by the 121% yield; indicative of the requirement for prelab calculation. The results of the

melting point analysis and TLC partaken to analyze the purity of salicylic acid acetylation were suggestive

1
Cerny, KF; Schwartz MH; Katz CE. Laboratory Manual for Organic Chemistry. “Aspirin Synthesis –
Alternate (Non-Microwave) Procedure” pg. 133
of the presence of impure aspirin in the product, but indistinctly hinted at the remaining presence of

unacetylated salicylic acid, enabling the conclusion of an uncompleted reaction process. The melting

point of the product ranged from 141OC to 145OC. The melting point of salicylic acid is 158.6 OC, while

the melting point of acetylsalicylic acid is 136 OC. The median of the melting point range of the product

was 2.2 times closer to that of acetylsalicylic acid than that of salicylic acid. The TLC analysis used an

excess of analyte which enabled the observation, of a faded area at a mobile phase retention distance

similar to that of salicylic acid’s at 4.75 cm giving a retention factor of 0.731, but a majority of the area

was proximal to the partner’s a mobile phase retention distance, which had a retention factor of 0.154,

giving a retention factor of 0.346. This was 61% closer to the previously determined retention factor for

aspirin, 0.48, than the retention factor determined for salicylic acid, providing evidence that the product

was aspirin or a mixture with similar stationary phase affinity of silicate, but also providing evidence of

incomplete aspirin formation. The final indicative assay determinative of the remaining presence of

salicylic acid was the ferric chloride test. This test formed a gradient going from burgundy to maroon,

which are undeniably shades of purple, thus proving the presence of phenols and thus incompletion of

reaction. This was possibly due to the addition of an insufficient quantity of phosphoric acid, preventing

protonation of the leaving acetate group, therefore rendering the reaction partially incomplete with

Questions:

1. The concentrated phosphoric acid was used to protonate the acetic anhydride, increasing its
electrophilicity, as well as to serve as an electrophile in its deprotonated form to deprotonate
the recently acetyloxy group and enabling the protonation of the ester group proximal to the
phenol ring, which enables the formation of the acetyl- leaving group, finally reprotonated
leaving acetylsalicylic acid.
2. .250 grams *(1/138.12 g/mol SAMM)= 0.00181002027 moles

*180.157 g/mol ASAMM =0.32608782218 grams

3. 325 mg = 65 mg * 5 grains