PRÁCTICA 3 Aislamiento de ácido acetilsalicílico del AlkaSeltzer y Otros ingredientes activos de analgésicos comerciales.

1.- OBJETIVO GENERAL: Extraer y aislar de una muestra comercial de aspirina, el ácido acetilsalicílico, determinar su punto de fusión y comprobar el porcentaje (en peso) del ácido extraído de la pastilla comercial de acuerdo a lo reportado por el fabricante. Comparar los puntos de fusión del producto sintetizado con el producto extraído.

MATERIALES:

vasos de precipitados de 50 mL.

gotero o una pipeta de plástico

cilindro de 10 mL

embudo

soporte universal

pinza de tres dedos

agitador de vidrio

papel filtro REACTIVOS: • pastillas de algún medicamento efervescente que contenga aspirina y bicarbonato de sodio (por ejemplo: Alka Seltzer) • ácido clorhídrico (HCl) 6M (se puede utilizar la presentación industrial, que se conoce como ácido muriático). • Agua (H2O) PROCEDIMIENTO: 1. En un vaso de precipitados de 50 mL coloca la pastilla del medicamento elegido y 10 mL de agua. Espera a que termine de reaccionar. Puede quedar algo de sólido sin disolver. 2. Vierte en otro vaso de precipitados de 50 mL aproximadamente 10 mL de ácido clorhídrico y adiciónalo a la solución del medicamento, en porciones de 5 gotas, utilizando el gotero o la pipeta de plástico. Al principio el sólido insoluble que se encontraba en el fondo del vaso se disuelve, con desprendimiento de burbujas de CO2, ya que se trata de bicarbonato de sodio. 3. Una vez que se termine el bicarbonato, la aspirina que se encuentra disuelta en la forma de su sal de sodio, acetisalicilato de sodio (CH3COOC6H4COONa), reaccionará con el ácido clorhídrico para formar el ácido acetilsalicílico que es insoluble en agua, por lo que precipitará:

CH3COOC6H4COONa + HCl CH3COOC6H4COOH + NaCl 4. Agrega ácido clorhídrico hasta que ya no se forme más sólido. 5. Filtra la suspensión que tienes en el vaso, y enjuaga el sólido (aspirina) que queda en el papel filtro con dos porciones de dos mililitros de agua helada.

Comentario [J1]: Se puede colocar la

solución en baño de hielo para favorecer la

precipitación mientras se adiciona el HCl

Comentario [J2]: Se sugiere

“estandarizar” la práctica para establecer un

rango de volumen de HCl que garantice la

formación de la mayor cantidad de

precipitado

6. Secar la muestra muy bien. Determine el peso y el punto de fusión. 7. Calcule el % de ácido acetilsalicílico presente en la muestra comercial, y compárelo con los valores reportados por el fabricante en el empaque. 8. Lava el material que utilizaste. 9. Guardar la muestra para su comparación por TLC con la aspirina a sintestizar en la práctica 4 Bibliografía

UNIVERSIDAD AUTÓNOMA DE AGUASCALIENTES. CENTRO DE BACHILLERATO Y SECUNDARIA. DEPARTAMENTO DE QUÍMICA. LABORATORIO DE QUÍMICA. MANUAL DE PRACTICAS DE LABORATORIO DE QUÍMICA A MICROESCALA PARA LA MATERIA DE QUÍMICA II DEL QUINTO SEMESTRE DE BACHILLERATO. UAA, Centro de Bach. y Sec., Departamento de Química, Ing. Jorge H. Ramírez Alonso, Julio 2006

IDENTIFICATION OF ACTIVE INGREDIENTS IN ANALGESIC DRUGS

The structures of the three active ingredients from common pain pills are shown below.

STRUCTURE

ACTIVE

INGREDIENT

Acetylsalicyclic

acid

Acetaminophen Ibuprofen

Purpose of the experiment: For this lab, you will be introduced to a technique called

thin layer chromatography (TLC). This technique can be used to identify all the

components in a mixture. In this experiment, you will use this technique to identify

analgesic drugs by isolating the active ingredients from these drugs. You will work in

groups of three, and each member of the group will isolate the active ingredient in one

of the three drugs. You will then share your sample with other members of the group.

Procedure:

1. Isolation of active Ingredient

Choose one of the three unknown tablets. Record the exact weight of the tablet before

proceeding. Crush the tablet between a folded piece of weighing paper. Place the

powder in a 3 mL conical vial, add about 2 mL of methanol, cap the vial and shake

vigorously. Allow the solution to sit and settle for a few minutes. Transfer the cloudy

solution (supernatant) to a 16 x 125 mm test tube. Repeat the extraction process by

adding an additional 2 mL of methanol in the vial, and transfer the solution to the same

centrifuge tube that contains the first extract. Centrifuge the mixture for 2-3 minutes or

until the supernatant liquid is clear.

Prepare a 2 cm alumina column (or about 0.5g of alumina) using a Pasteur pipet and add

about 2 mL of methanol to wet the alumina. Allow the liquid to drain until the level of

methanol reaches the surface of the alumina. If necessary add more methanol but don’t

let the column run dry (in other words don’t let the methanol to drain below the surface

of the alumina). Carefully transfer the clear liquid from the test tube to the column

using the Pasteur pipet and collect the liquid that passes through the column in a small

beaker. Again wait for the liquid to reach the surface of the alumina, add an additional

1 mL of methanol and allow the solution to drain into the same beaker. This ensures

that the entire active ingredient in the analgesic drug has been eluted from the column.

At this point, keep a small amount of sample for TLC (see section 2).

For the rest of the sample, evaporate the solvent by placing the beaker in a warm sand

bath or a warm water bath at about 50-70ºC. When the solvent has completely

evaporated or until the remaining liquid is no longer evaporating remove the vial from

the water or sand bath and cool it down to RT. It is essential to complete the

evaporation within 10-15 minutes. Place the beaker in an ice-bath if necessary you can

scrape the inside of the beaker with a glass rod or spatula to induce crystallization.

If your crystals are wet after the evaporation filter the crystals using the Hirsch funnel

connected to a vacuum, break up the lumps and allow the solid to dry for 5 minutes on

the funnel. When the crystals are completely dry, determine the isolated weight.

Determine the melting point and calculate the % recovery.

2. Thin Layer Chromatography:

Obtain a TLC plate and a few micropipets from the reagents bench. Use a pencil and

lightly draw a line about 1 cm above the bottom of the plate. Mark the plate with six

points evenly spaced where the samples will be spotted, three knowns and three

unknowns. Obtain a few drops of the knowns in small test tubes.

Use a 250 mL beaker as a developing jar by introducing enough solvent to cover the

bottom of the jar to about 0.5 cm (about 10 mL). Introduce a filter paper folded to fit in

the jar, and cover the beaker with a watch glass. Allow the solvent to soak the filter

paper and let the atmosphere in the jar equilibrate. The sample can be applied on the

plate by gently spotting the tip of the filled capillary to the plate, and repeat the spotting

about 2-3 times depending on the concentration of the solution. Between each spotting,

allow the solvent to evaporate. The solvent used is 0.5% acetic acid in ethyl acetate.

Visualize the developed TLC plate under UV light and mark them with pencil. Place

the plate in the iodine chamber and mark the spot by indicating iodine active (IA).

Sketch the plate in your notebook with any necessary comments.

Calculate the Rf values and identify the three analgesic drugs. Confirm the identity of

your drug by recording an IR spectrum and comparing it with the authentic spectrum.

Label the important peaks in the IR spectrum that correspond to functional groups

present in the compound.

Questions:

1) Define Rf value.

2) Which compound in each of the two pairs below will have a larger Rf value if they

were both run on the silica gel TLC plate in 5% ethyl acetate/hexane: benzene or

benzoic acid, dimethyl amine or cyclooctanone? Explain your reasoning.

3) If a 625 mg Tylenol tablet contains 81% acetaminophen how many moles of

acetaminophen are present in the tablet?

4) What will be the result of the following errors in TLC technique?

a) Solvent of too high polarity

b) Solvent pool in developing jar too deep

c) Forgetting to remove the TLC plate when the solvent has reached the top of the

plate

d) Forgetting to mark the solvent front immediately after the removal of the plate

from the developing chamber.

References:

1) Mayo, D. W.; Pike, R. M.; Trumper, P. K. Microscale Techniques for the

Organic Laboratory; Wiley & Sons: New York 2001.

2) Pavia, D. L.; Lampman, G. M.; Kriz, G. S.; Engel, R. G. Introduction to

Organic laboratory Techniques, A Microscale Approach; Saunders College

Publishing: Fort Worth 1999.

3) Padias, A. B. Organic Chemistry, Laboratory Manual; Hayden McNeil

Publishing: Plymouth 2001.

Loosen the cap a few times during the mixing process to release any build up of

pressure in the vial.

Don’t forget to balance your centrifuge tube with another test tube of the same

volume. You can accomplish this by using another lab mate’s test tube or a test tube

that containing water.

With a second Pasteur pipet, insert a small piece of cotton or glass wool through the

top and wedge gently in the constriction of the pipet. Use a paper towel to cover the

narrow part of the pipet tip and break off the tip to a length of about 2 cm. Clamp the

pipet in a vertical position so that the liquid from the column drains into a small beaker.

Add alumina and tap the column with your finger to pack the alumina.

To speed up the evaporation, direct a gentle stream of air into the vial.

The volume of the solution should be less than 0.5 mL before you stop the evaporation

process. Ibuprofen has a low melting point so it might be melted during the

evaporation.

Aspirin will partially decompose if you heat it too long.

REVISAR:

TECNICAS DE EXTRACCION, PUNTO DE FUSION

ANALGESICOS COMERCIALES MAS COMUNES, SUS EXCIPIENTES, ETC. Y

SUS USOS.

SINTESIS DE LOS TRES ANALGESICOS DE ESTA PRACTICA

TRAER

TABLETAS DE ALKASELTZER

ACETAMINOFEN , IBUPROFENO

TIENEN QUE SER PASTILLAS BLANCAS SIN COLORANTES.

Envases de heces pequeños par guardar lo ingredientes activos