Experiment 4. Reactions of Carboxylic Acids & Their
Derivatives.
References: Solomons & Fryhle, Chapter 18
INTRODUCTION:
This experiment is in two parts. The first is a conversion of a carboxylic acid to a fragrant ester. The second part consists of a couple of simple test tube reactions that illustrate some of the properties of carboxylic acids and various derivatives.
BACKGROUND:
Significance of Esters in Biology
Esters are very important in biology, with extensive applications in medicine and industry. In medical applications, the body interacts with some types of esters which are used as anesthetics. For centuries the Amerindians of the Andes have been using the leaves of the 'Coco bush'
(Erythroxylon coca) as a mild stimulant. In due course, chemists investigated the components of the coco leaves, and finally the active alkaloid "cocaine", was isolated pure in 1862. In the following years its properties were investigated, and by the 1880's it was in use as an anesthetic in surgery and dentistry, one of the first such drugs to alleviate pain in medical procedures. However, it was quickly realized that cocaine also had two major disadvantages. First, the lethal dose was not a great deal more than the therapeutic dose, and so safe administration of the drug in surgery was unreliable. Secondly, cocaine causes serious problems, like potentially
irreversible damage to the central nervous system.
Consequently, as soon as the structure of cocaine was established (in 1910), chemists began preparing analogues. An example is "Novocaine", which is one of the most successful synthetic drugs in this family. A simpler analogue is "Benzocaine", used extensively as a topical pain reliever, for example in treating sunburns.
Fischer Esterification
Esters are carboxylic acid derivatives and can be obtained by combining and heating an alcohol with a carboxylic acid in the presence of an acid catalyst, like sulfuric acid.
The yield can be increased by using a large excess of one of the reactants or by constantly removing the products from the reaction mixture (LeChatalier’s principle).
Fragrant Esters
In this experiment we will examine fragrant esters that interact with the olfactory system in the nose. The organoleptic qualities (odours and flavours) of fruits and flowers are
compounds with ester functional groups. They can be due to a single ester, but are often due to a mixture of compounds in which the ester(s) is/are the predominate compound(s).
We will perform a Fischer Esterification reaction using acetic Octanol, 1-propanol, Iso-pentanol and 1
different olfactory activity.
Part B: Tests of Carboxylic Acids, their Salts and Derivatives
(a) Salt Formation
Carboxylic acids may be neutralized by strong bases to give salts. Acids which may be only slightly soluble in water can be extracted from their solutions in an organic solvent by aqueous base, as the salts are usually water
(b) Salt Hydrolysis
Most carboxylic acids are only partially dissociated in aqueous solution. Consequently, when the salt of a carboxylic acid is dissolved in water, it is partially hydrolyzed to the undissociated acid and hydroxide ion: RCOO-Na+ + H
(c) Acid Chlorides
The halide ion is a good leaving group making acid halides very reactive towards nucleophilic acyl substitution. Acid halides are so reactive that they are not found in nature, since they even react with water (R' = H): RCOCl + HOR'
(d) Amides
Values of pKa for amides of carboxylic acids are in the range of 15 comparable in acidity to alcohols.
ivatives and can be obtained by combining and heating an alcohol with a carboxylic acid in the presence of an acid catalyst, like sulfuric acid.
The yield can be increased by using a large excess of one of the reactants or by constantly oducts from the reaction mixture (LeChatalier’s principle).
In this experiment we will examine fragrant esters that interact with the olfactory system in the nose. The organoleptic qualities (odours and flavours) of fruits and flowers are often due to compounds with ester functional groups. They can be due to a single ester, but are often due to a mixture of compounds in which the ester(s) is/are the predominate compound(s).
We will perform a Fischer Esterification reaction using acetic acid and 4 different alcohols (1 pentanol and 1-butanol). Each of the products in this experiment show
Part B: Tests of Carboxylic Acids, their Salts and Derivatives
Carboxylic acids may be neutralized by strong bases to give salts. Acids which may be only slightly soluble in water can be extracted from their solutions in an organic solvent by aqueous base, as the salts are usually water soluble: RCOOH + NaOH ---> RCOO-Na+ + H
Most carboxylic acids are only partially dissociated in aqueous solution. Consequently, when the salt of a carboxylic acid is dissolved in water, it is partially hydrolyzed to the undissociated acid
+ H2O ---> RCOOH + NaOH.
The halide ion is a good leaving group making acid halides very reactive towards nucleophilic acyl substitution. Acid halides are so reactive that they are not found in nature, since they even
water (R' = H): RCOCl + HOR' ---> RCOOR' + HCl.
for amides of carboxylic acids are in the range of 15-17, which means that they are comparable in acidity to alcohols.
ivatives and can be obtained by combining and heating an alcohol
The yield can be increased by using a large excess of one of the reactants or by constantly
In this experiment we will examine fragrant esters that interact with the olfactory system in the often due to compounds with ester functional groups. They can be due to a single ester, but are often due to a mixture of compounds in which the ester(s) is/are the predominate compound(s).
acid and 4 different alcohols (1-butanol). Each of the products in this experiment show
Carboxylic acids may be neutralized by strong bases to give salts. Acids which may be only slightly soluble in water can be extracted from their solutions in an organic solvent by aqueous
+ H2O.
Most carboxylic acids are only partially dissociated in aqueous solution. Consequently, when the salt of a carboxylic acid is dissolved in water, it is partially hydrolyzed to the undissociated acid
The halide ion is a good leaving group making acid halides very reactive towards nucleophilic acyl substitution. Acid halides are so reactive that they are not found in nature, since they even
PRE-LAB PREPARATION:
1. Write out a mechanism for the formation of the Novocaine, by reacting para-aminobenzoic acid with 2-diethylamino-ethanol under acidic (H+) conditions. (See Background section for structure of Novocaine)
2. Using the acetic acid and the 4 different alcohols (Octanol, propanol, Iso-pentanol and 1-butanol), draw the expected ester products.
3. Write out the structures of all compounds to be tested in Part B.
EXPERIMENTAL PROCEDURE:
Safety and Disposal Data for Compounds Used.
Compound Mol. Wt. (g/mol) Safety and Disposal Data
Acetamide
Acetic Acid
Aniline
Benzoic Acid
Ethylamine
Sodium Acetate
5% Sodium Bicarbonate
10% Sodium Hydroxide (NaOH)
Sodium Sulfate
Conc. Sulfuric Acid (H2SO4)
Unknown Alcohols
59.06
60.05
93.12
122.12
45.08
82.03
84.00
39.99
142.03
98.07
---
Harmful. Possible risk of irreversible effects. Use gloves when handling. Dispose in ‘Waste Solid’.
Corrosive. Flammable. Harmful if swallowed or inhaled. Dispose in ‘Inorganic Acids and Salts’.
Toxic. Dangerous for the environment. Harmful by inhalation, in contact with skin and if swallowed. Dispose in ‘Waste Solid’.
Harmful if swallowed. Irritating to eyes. Dispose in ‘Waste Solid’.
Extremely flammable. Irritating to eyes and respiratory system. Dispose in Organic Waste.
Avoid contact with eyes and skin. Wear gloves when handling. Dispose in ‘Waste Solid’.
Avoid contact with eyes and skin. Dispose in ‘Inorganic Bases’.
Corrosive. Causes severe burns. Wear gloves when handling. Dispose in ‘Inorganic Bases’.
Irritating to eyes. Dispose in ‘Waste Solid’.
Corrosive. Causes severe burns. Avoid all contact. Wear gloves when handling. Dispose in ‘Inorganic Acids and Salts’.
Equipment Used
All the equipment needed to perform this experiment should be in one of the three drawers in the top row of your workstation, one of the drawers underneath your fumehood or the common counter for your TAs group.
However the microkit (microscale glassware) should be obtained directly from your TA. At the end of the experiment, return your complete microkit and get the TA to initial the return of your microkit.
Part A: Fragrant Ester Synthesis
1. Reaction of Acetic Acid with an ‘unknown’ alcohol
a) Using a pipette, place at least 2.5 mL of acetic acid in a 10 mL cylindrical vial and add approx. 1 mL of your ‘unknown’ alcohol. Add 3 drops of CONCENTRATED sulfuric acid
(CAREFULLY it BURNS!), followed by the addition of a boiling chip.
b) Attach a micro-condenser (with cooling water) and heat the mixture under reflux using the aluminum heating block on a heater-stirrer for at least 60 min. Take care not to overheat the flask and have too violent a reflux rate, but it must be REFULXING not just heating. It will take a while to adjust the temperature until you achieve a steady reflux.
[Note: This may be a good time to do Part B. You will also run an NMR of the expected ester product during this time. You will be taken to the NMR in ABB 409 & shown how this is done.] c) After the 60 min reflux period and the mixture is clear, remove the heat and allow the vial to cool (you may use a beaker of cold water if you wish to hasten cooling).
2. Isolating the Ester
a) When the vial is cool, add 2mL of 5% sodium bicarbonate solution to neutralize the mixture. Cap the vial and invert it several times to mix the layers. Frequently VENT the system to release the pressure by momentarily unscrewing the cap (This is like a mini extraction!). Then allow the mixture to settle.
b) Using a pipette, remove the aqueous layer (bottom layer) from the vial. Try to remove the entire aqueous layer.
c) Repeat steps a) and b) with another 2 mL portion of 5% sodium bicarbonate.
d) Transfer the remaining organic layer to a conical vial and check that there is only one phase. e) Dry the organic layer by adding anhydrous sodium sulfate little by little with a microspatula until the solid no longer clumps together at the bottom of the vial but runs freely in the liquid. f) Using a filtering pipette (see Microscale Techniques) transfer the liquid to a clean, dry 3mL conical vial (NOT a 5mL conical vial).
3. Purifying the Ester
If you have less than 0.5 mL, check with your TA on whether to purify or not.
b) Transfer you final distilled product to a clean vial.
4. Characterization of your Ester
a) Obtain and label an IR spectrum of your final (distilled) product.
b) Label the NMR that was obtained earlier in the lab (you should refresh yourself on 1H NMR prior to the lab).
c) Note the odour. [Recall: Smelling solutions is done by wafting the smell towards your nose, don’t directly inhale!].
See if you can identify the fragrance or flavouring additive of which your ester is a major component. You may find you can’t easily recognize your ester, since these aromas are often a mixture or in conjunction with taste (DO NOT taste your product). If it smells like vinegar then there is still acetic acid (the main component of vinegar) in your mixture.
Major Ester in Fragrances and Flavours Agents
Ester Aroma
Butyl Acetate Apple
Iso-Pentyl Acetate Banana Octyl Acetate Oranges Propyl Acetate Pear
d) Dispose your product in the ORGANIC WASTE jar provided.
Part B: Tests of Carboxylic Acids, their Salts and Derivatives
DO ALL TESTS IN A FUMEHOOD!!!
(a) Salt Formation
In each of two test tubes, place approx. 0.1 g of benzoic acid. To one tube add 3 mL of cold water, to the other add 3 mL of 10% sodium hydroxide solution. Shake both tubes, observe, and record the results.
(b) Salt Hydrolysis
Dissolve approximately 0.2 g of sodium acetate in 5 mL of distilled water, test the resulting solution with litmus paper, and note the result.
(c) Acid Chlorides DO IN THE HOOD!!!!!!
Put approx. 0.5 mL of your ‘unknown’ alcohol in a test tube. Add, drop by drop, 1 mL of acetyl chloride and test any vapour evolved with moist pH paper while you allow it to stand for about 2 minutes.
(d) Amides
