Designer Molecules - Esterification

Designer Molecules
Esterification

Introduction
Biochemists who are interested in creating anticancer drugs often try to synthesize a drug that is similar to substances found in natural sources like plants and animals. Sometimes by changing a small part of the molecule, by altering a small part of its molecular structure, chemists can change the properties of it.

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Safety
Materials
Procedure
Data Analysis
Implications and Applications

The process of discovering what changes to make to molecules for a specific end (like making it into a drug) can be thought of as "designing molecules." The molecules in anticancer compounds are complex, but you can get an idea of how chemists design molecules for specific functions by working with simpler compounds called esters.

Esters are an important class of organic compounds that often have pleasant odors and are responsible for many distinctive smells in fruits and flavorings. How do chemists make specific esters with desired odors? Esters can be readily prepared from a carboxylic acid and an alcohol. Choosing the right combination of alcohol and acid determines the odor.

Safety

General Safety Guidelines

Wear protective goggles throughout the laboratory activity.
Be very careful with the concentrated sulfuric acid. It can cause serious chemical burns.
Your teacher will demonstrate the correct method for testing for odors using a wafting technique; you should never directly smell any substance used or prepared in the laboratory.

Materials
(For 24 students working in pairs)

12 test tubes, 10 cm, fitted with one-hole cork stoppers (do not use rubber stoppers)
12 large-barrel polyethylene pipettes (e.g., Beral^®)
12 beakers, 100 ml
12 ring stands, wire screens and burners or hot plates
Boiling stones
12 labeled 10-ml bottles of concentrated sulfuric acid (H₂SO₄), with polyethylene pipette
8 labeled test tubes, 10-cm with pipettes, containing the following alcohols: methanol, ethanol, 1-octanol, 2-methyl-1-butanol, isobutanol, 1-propanol, isoamyl alcohol, benzyl alcohol
6 labeled test tubes, 10-cm with pipettes, containing the following acids: formic acid, acetic acid, propionic acid, butyric acid, salicylic acid, anthranilic acid

Alcohols used in this experiment:

Carboxylic acids used in this experiment:

Procedure

Place 75 ml of water in a 100-ml beaker, add a boiling stone, and set the beaker on a wire screen on a ring stand. Light a burner and place it under the beaker. Bring the water to a gentle boil. (If available, hot plates should be used.)

Examine the structure of the ester you wish to synthesize. Determine which carboxylic acid and which alcohol you need to use in your synthesis.

In a 10-cm test tube obtain 1 drop of a carboxylic acid. If the carboxylic acid you wish to use is a solid, use about the amount that would fit inside this letter "O." Add 3 drops of alcohol and 1 drop of concentrated sulfuric acid. Be very careful with the sulfuric acid. It can cause severe burns if spilled on the skin.

Drop a boiling stone into the mixture. Use caution.

Before heating, wave the fumes from this mixture to your nose and carefully note and record the odor of this reaction mixture.

Stopper the test tube with a one-hole cork stopper and set the assembly in the boiling water. If the test tube will not “stand up” in the beaker without getting water in the tube, put a test tube clamp around the tube to hold it upright in the beaker.

Turn off the heat and allow mixture to stand in the hot water for 5-10 minutes.

Use a test tube clamp to remove the reaction assembly from the water bath.

Fill a Beral^® polyethylene pipette with cold water and empty its contents into the test tube. Mix the solution by gently swirling the test tube.

Remove a small quantity of the aqueous mixture from the test tube with the pipette. One way to do this without exposing yourself to the mixture in the tube is to push the tip of the pipette into the cork until the pipette shaft fills the hole in the stopper. Turn the tube so that the liquid in the tube covers the pipette tip and draw up some of the mixture. Then turn the test tube right side up and withdraw the pipette.

Once the pipette is removed from the tube, invert it to let the liquid flow from the shaft to the bulb. Clear the liquid out of the shaft by lightly tapping the side or by drawing some air into the pipette.

With the pipette in the inverted position, carefully force out some of the vapor and wave the fumes to your nose. Carefully note and record the odor of the ester you synthesized.

Occasionally, the vapor is too concentrated and it will "overpower" your sense of smell. Add more water to the mixture in the test tube to dilute the odor.

If the odor is too faint, place the bulb of your pipette in warm water, wait for a minute, and try again.

Thoroughly wash your hands before leaving the laboratory.

Data Analysis
Compare your ester's odor with the odor you expected from its name (grape, orange, etc.) Determine the ester's structure from the list above. Write a complete balanced equation for the synthesis of your ester.
Implications and Applications

In some cases the odor of the synthesized ester does not exactly match the odor of the fragrance found in nature. What might be a possible explanation?

Some of the compounds in the list of fragrances have functional groups in addition to the ester group. Identify these compounds and determine the types of functional groups present with the help of the functional group chart posted.

For more information, at other Web sites...

Medicines by Design — from the National Institute of General Medical Sciences, National Institutes of Health.

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