Synthesis of aspirin

Objective

The purpose of this experiment is to familiarize the students with the reaction of esterification getting aspirin (acetyl salicylic acid) from the salicylic acid and acetic anhydride.

2-methyl-2-propanol terbutanol t-BuOH trimethyl carbinol DKGAVHZHDRPRBM-UHFFFAOYSA-N
Aspirin BSYNRYMUTXBXSQ-UHFFFAOYSA-N
3D structure

Background

Acetylsalicylic acid is marketed under the name of aspirin for the home Bayerbeing one of the drugs most consumed in the world. It was synthesized at the end of the last century by the German chemist Felix Hofmann.

It uses a reaction of esterification catalyzed acid (H2SO4 or H3PO4 ), where the salicylic acid treated with acetic anhydride gives acetylsalicylic acid (aspirin). In this reaction, it becomes a hydroxyl group to an ester, obtained as a by-product acetic acid.

Synthesis of aspirin BSYNRYMUTXBXSQ-UHFFFAOYSA-N

It is a drug that is found in the list of essential medicines of the WHO. Acts as antipyretic, and mainly as an analgesic. As antipyretic exerts its effect on two levels: it increases the heat dissipation by vaso-dilation (action not significant), and acts on the thermostat hypothalamic, which is the central regulator of the body's temperature.

Their administration route is oral, as it is well absorbed from the gastrointestinal tract. The acetylsalicylic acid may be partially hydrolyzed; this, in addition to noticed easily by the smell of acetic acid, it can be recognized by a trial with FeCl3 and seeing if it produces violet colour.

Reaction mechanism

The reaction is catalyzed by acid (phosphoric acid, H3PO4). In a first step occurs the protonation of acetic anhydride as shown in the figure.

This is going to promote the reactivity of acetic anhydride, which is positively charged at one of the carbons. It is a reaction of esterification of phenol involves the breaking of a link OH, and is carried out with acetic anhydride.

In a second step, there is an addition: the electron pair of the phenol attacks the carbon positively charged acetic anhydride.

synthesis of aspirin mechanism of reaction acido salicilico acido acetico acido acetil salicilico

In a third step happens a removal: producing acetic acid and acetyl salicylic acid protonated. The fourth and last step it is a deprotonation by the effect of the water that is added at the end of the reaction.

Experimental procedure

Place 3 g (0.022 mol) of salicylic acid in a flask of 100 ml. Then, add 6 ml of acetic anhydride and then 6 to 8 drops of phosphoric acid (H3PO4) of 85 %. Subsequently, stir gently to mix the layers and dipped the flask connected to a reflux equipment in a bath of hot water (70-80 °C) for 15 min.

¡DANGER! "The acetic anhydride reacts violently with water and the mixture may splatter."

 

Moves the flask from the bath and, while still hot, is added drop by drop to about 1 ml of water, stirring after each addition. Once you have added the first ml of water, can already added quickly, another 20 ml of the same.

The flask is cooled in an ice bath, with what the product should begin to crystallize. Filters empty and to calculate the performance of the dry product (performance estimated 70 % and melting point 134-136 ° C).

International Chemical Identifier

The IUPAC InChI key identifiers for the main compounds used in this experiment are provided to facilitate the nomenclature and formulation of chemical compounds and the search for information on the Internet for these compounds.

acetic acidQTBSBXVTEAMEQO-UHFFFAOYSA-N 
acetyl salicylic acidBSYNRYMUTXBXSQ-UHFFFAOYSA-N
phosphoric acidNBIIXXVUZAFLBC-UHFFFAOYSA-N
salicylic acidYGSDEFSMJLZEOE-UHFFFAOYSA-N
acetic anhydrideWFDIJRYMOXRFFG-UHFFFAOYSA-N

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