Synthesis of Organic Compounds

Experiment 9

INTRODUCTION

Organic compounds are common here on Earth. Of the wide number of known ones, most are synthetically-prepared rather than isolated from nature. With that, synthesis of organic compounds has become an important and developed branch of Chemistry. Organic synthesis is a special branch of chemical synthesis concerned with the construction of organic compounds by means of organic reactions.

Reasons for synthesizing compounds include proof of structure of a natural compound by combining simpler molecules and facilitating product formation through specific organic reactions, and to prepare specific compounds to study reaction mechanisms or biological mechanisms. In preparing a known

compound, a published setup appropriate for the work is

followed. The choice may vary according to the available starting materials, laboratory equipment, chemist's experience and the experimental advantage.

The simplest synthesis of a molecule is one in which the target molecule can be obtained by submitting a readily available starting material to a single reaction that converts it to the desired target molecule. Organic synthesis, then, plays an important role by allowing for the creation of specific molecules for scientific and technological investigations.

METHODOLOGY

D Y E

In a 50-mL beaker, 0.9 mL of aniline, 1.4 mL of water, and 2.1mL of concentrated hydrochloric acid were combined. The contents were then cooled to a 0-5 C and then 1 g of ice was added. Solution of sodium nitrate was dropped until the reaction mixture contained excess acid. It was then tested for excess nitrous acid by spotting a drop on the starch-iodide paper. The

temperature of the reaction mixture was kept below 5 C. To

prepare the alkaline solution, 1.4 g of -naphthol was dissolved in 3 mL of a 3M aqueous sodium hydroxide.

It was cooled then to 5 C and phenyldiazoniun chloride was added with stirring. The reaction was allowed to stand for 15 minutes at 0-5 C. The product was collected by gravity filtration on fluted filter paper washed with several portions of cold water. The product was weighed (however, the percent yield was not calculated anymore). In testing the products for physical properties, the appearance, color, texture and odor of

the product were noted. Its melting point was also determined.

For chemical tests, a pinch of the product was

dissolved in 5 mL of distilled water. Three drops of this

solution were added to a test tube with 2 mL of 0.1 M

NaOH. The same procedure was repeated using 0.1 M

HCl, NH4OH, and CH3COOH.

SOAP

2.5 grams of NaOH was dissolved in 5-mL water and 10 mL of 95% CH3COOH. The solution was then added to 5 grams of hydrogenated shortening in a 150-mL beaker. The beaker was covered with a watch glass and heated in a water bath that was previously prepared. 50% of alcohol was added with constant stirring to maintain the consistency of the solutions volume. A clear homogenous solution was then obtained and all the

melted fat was completely dissolved. The soap was diluted with
15 mL water and was poured in a brine solution.

The mixture was stirred thoroughly as the precipitated soap was collected using a fluted filter paper. The product was washed twice with 10-mL portions of cold distilled water. 2 grams of crude soap was dissolved in 10-mL portions of cold distilled water and was set aside for tests. The remaining soap was placed in an evaporating dish, heated in a water bath with

constant stirring, until it formed a thick solution. To account for

the physical properties of the product, the appearance, color, texture, and odor were recorded along with its melting point.

Chemical tests were done on the final product. The products pH was obtained using a litmus paper. 1-mL of dilute calcium chloride was added to 10-mL of the soap solution. The same procedure was done using dilute magnesium chloride and ferric

chloride solutions. Hydrochloric acid was added to 50-mL of the

soap solution until it is an acid to Congo red. The mixture was cooled and the precipitates were collected in a fluted filter paper. The final product was tested for solubility in 2-mL methylene chloride.

ASPIRIN

Two grams of salicylic acid were placed in a 125Erlenmeyer flask. Five milliliters of acetic anhydride and 5 drops of 85% phosphoric acid were added. The flask was heated in the hot water bath for 5 minutes. After removing

from heat and while still hot, 2 mL of water was added.

After decomposition is complete, 40 mL of water were added until crystals begin to form. The product was collected by suction filtration.

The product was washed and dried. It was then recrystallized from 35 mL of hot water with the use of decolorizing charcoal

and then weighed. In testing the products for physical

properties, the appearance, color, texture, and odor of the product were noted. Its melting point was also determined. For

chemical tests, a few crystals of aspirin were dissolved in 1 mL

of methanol in a test tube and 1% ferric chloride solution was added. The test was repeated using salicylic acid. The results were recorded.

RESULTS

Physical Properties: DYE

Appearance: fine powder Color: orange-red Texture: fine, powdery Odor: same as that of paint Melting Point: was not noted [131-132 C, theoretical]

Chemical Test

Observation

0.1 M NaOH

Least intense

1. M HCl

Most intense

NH4OH

Moderately intense

CH3COOH

Intense

The synthesis of 1-Phenylazo-2-naphthol, or Sudan 1, involves

two steps: the first being the preparation of a solution of

diazonium salt, benzene diazonium chloride from aniline. In this process, the aniline reacts with sodium nitrate in extremely acidic medium by using HCl or H2SO4. The reaction yields phenyldiazonium chloride and the process is called

diazotization. The reaction is shown below:

The nitrous acid in the reaction is from the reaction of HCl and NaNO2. It is formed prior to its use because it is very unstable. The diazotization reaction yields a very reactive salt, the phenyldiazonium chloride.

Phenyldiazonium chloride solution was then reacted with -naphthol in NaOH. The reaction is called diazonium-coupling reaction, in which the diazonium salt attacks the carbon in the ortho- and parapositions with respect to the activating group attached to the benzene. In the experiment, the -naphthol

couples with the diazonium salt.

The compound that is formed is 1-phenylazo-2naphthol or Sudan-1, a precipitate that is orange-red in color.

Physical Properties: SOAP

Appearance: slushy white substance Color: white Texture: soft Odor: same as that of ethanol Melting Point: was not noted [135-145C, theoretical]

Chemical Test
pH

Observation
basic

Formation of precipitate Calcium chloride

Magnesium chloride Ferric chloride [Ch3(CH2)14CO2-]2 Ca+ + 2Na+ [Ch3(CH2)14CO2-]2 Mg+ + 2Na+ [Ch3(CH2)14CO2-]3 Fe+ + 3Na+ miscible

Oil with soap

Oil with water

immiscible

This involves the alkaline hydrolysis (reaction with water or dilute alkali) of triglyceride (fat or oil). Triglyceride is reacted with lye (NaOH solution) or other strong bases such as KOH to

produce glycerol and fatty acid salts. The fatty acid salt is the
soap. Saponification is the term used when hydrolysis of esters are done to produce soap.

The ester functional groups are hydrolyzed releasing its alcohol portion as glycerol and the acid portions as a mixture of the sodium salts of the fatty acid. The glycerol is water-soluble and

is separated from the fatty acid salts. These are nearly insoluble
in water, and are washed and compressed into a cake which is the soap. The reaction is shown below.

The bond between the fatty acid and the glycerol backbone is referred to as an ester linkage. In the saponification process, the ester linkage is broken to form glycerol and soap. The reaction mechanism is based on nucleophilic acyl substitution. It is easier to look at a simple ester than a fat to illustrate how the mechanism works.

First step of the reaction mechanism. Here, the hydroxide ion from NaOH attacks the carbonyl group of the ester to give an orthoester.

Second step of the reaction mechanism. The orthoester rearranges to form a carboxylic ester and an alkoxide.

Third step of the reaction mechanism. Proton transfer

takes place since the OR group is more basic than RCOOH. The products formed are alcohol and salt. In

saponification, the alcohol is the glycerol and the salt of

the fatty acid is the soap.

Due to the stability and lack of reactivity of the carboxylate

anion with most nucleophiles (in this reaction, the hydroxide or

alkoxide ions), this reaction is not reversible. Sodium and potassium salts are generally soluble in water, and

potassium soaps are usually softer than sodium soaps. When

these metals are replaced by calcium, iron, or magnesium ions, the new carboxylate salts are no longer soluble in water; and form what we refer to as soap scum.

You may have heard of the terms "hard water" or "soft water". Hard water is water that contains many metal ions such as iron, calcium, and magnesium ions. Soft water contains less of these

ions. Therefore, when we use soap with hard water, these ions
replace the sodium or potassium ions.

Physical Properties: ASPIRIN

Appearance: white powdery substance

Color: white
Texture: powdery Odor: none

Melting Point: was not noted [136C, theoretical]

Aspirin or acetylsalicylic acid is prepared by reacting salicylic acid with acetic anhydride in a process called esterification. Esterification is the acid-catalyzed reaction of a carboxyl (-

COOH) group and an -OH group of an alcohol or phenol to form

a carboxylate ester.

The -OH group is the phenolic -OH group attached to ring of the salicylic acid. The acetyl group, -COCH3 comes from acetic anhydride, and the reaction is catalyzed by phosphoric acid.

The H+ from an acid catalyst protonates the carbonyl oxygen of

acetic anhydride to make the carbonyl groups more susceptible

to nucleophilic attack. This is followed by the attack of the nucleophile, the phenolic group, to the carbonyl group to which the protonated oxygen is attached. Proton transfer follows. The hydrogen from the phenolic group of the nucleophile forms a

bond with the oxygen adjacent to the carbon that is doubly

bonded to another oxygen.

Acetic anhydride is formed by the departure of the leaving group. Finally, proton transfer happens again to form acetylsalicylic acid. The H+ is regenerated. The main impurity or by-product for the reaction is excess salicylic acid, which will coprecipitate with the Aspirin if the procedure is done too quickly.

To assess the purity of the product, ferric chloride is used. It

reacts with phenol to form a purple solution. If the product turns gives a purple color with ferric chloride solution, it means that not all of the salicylic acid has been consumed. Thus, the product is impure.

GUIDE QUESTIONS

Why should the temperature of the reaction be kept

below 5C?

The diazonium salt will easily decompose back to aniline if the advised temperature is not followed. This will give a low percent yield for the reaction.

Explain the principle behind the use of starch iodide paste in detecting excess nitrous acid.

Nitrous acid oxidizes iodide ion to form iodine. The iodide ion in starch reacts with nitrous acid to form a blue complex. So if there is already a blue color on

your starch-iodide paper, there is already excess

Nitrous acid since all I- have been oxidized to I2.

Why is the rate of coupling of phenyldiazonium ion

with -naphthol dependent upon the pH of the reaction medium?

If the acidity of the reaction medium is high, the amines will be converted to ions. When this happens, they cannot undergo aromatic substitution reaction.

Thus, the coupling reaction will be slow if the acidity

of the reaction medium is high.

Applications:

Many dyes are also used as acid-base indicators. An example of this is Congo red which is red in basic solutions and blue in acidic solutions. With the aid of your text, draw the structure of Congo red. Write the equation for the probable method of synthesis of

Congo red (diazotization and coupling reactions only)

In the red form, Congo red may be considered to be a salt in

which the SO3 group is deprotonated form (after treatment with base). In the blue form, two protons are added to the molecule to give two substances (differing principally in the location of the protons) in equilibrium with each other. One of these has the protons added to the NH2 groups to form NH3 + groups. What is the probable site o protonation in the other substances (which is largely responsible for the blue color)? (It

is not the SO3 group!) Write two resonance structures for the
second protonated substance that will show the nature of the chromophore responsible for the blue color.

Why was the dilute soap solution poured in a solution of sodium chloride in water?

This is the process of salting out. The addition of NaCl solution to the soap solution will precipitate the soap.

Explain the result obtained when the dilute soap solution is treated with calcium chloride, magnesium chloride and ferric

chloride solutions.

Sodium and potassium salts are generally soluble in water, and

potassium soaps are usually softer than sodium soaps. When

these metals are replaced by calcium, iron, or magnesium ions, the new carboxylate salts are no longer soluble in water; and form soap scum. Thus, if you have successfully synthesized soap, soap scum should form when you test your product

with calcium chloride, magnesium chloride and ferric chloride

solutions.

How does the soap function as an emulsifying agent for oil in water? Draw a picture of an oil droplet and several soap

molecules to illustrate your answer.

The long hydrocarbon chain of the soap is non-polar and

hydrophobic (repelled by water). The "salt" end of the soap

molecule is ionic and hydrophilic (water soluble).

Soaps are "bridge" molecules. Their long hydrocarbon chains

are very much like oils, so they mix well with oils. In fact, we can say that the chains of soap dissolve in oils. At the same time, their ionic heads are polar enough to dissolve in water. If we imagine a small globule of oily material, which has dissolved

a bunch of soap molecules, we can see that the polar ionic

heads will stick out (insoluble in oil) at the surface. These polar bumps on the surface attract water molecules, so that the oily glob is coated with water molecules that are held there by the ions.

Applications:

Suppose that you wanted to emulsify a water-insoluble compound in water. Would soap be a reasonable choice for

the emulsifying agent if the water were slightly acidic? Why?

If it would not be a good choice, draw the structure of an organic molecule that might be more suitable.

No, because the soap will not be able to form a bridge between oil and water. This is due to the hydronium ions that will be attached to the polar end of the soap. When this happens, the soap will not interact with the water. Thus, the soap will not be

able to dissolve the water and an emulsion wont happen.

A detergent can be used instead because it can tolerate acidic conditions. Its structure can bind with hydronium ions, water and oil.

A detergent can be used instead because it can tolerate acidic conditions. Its structure can bind with hydronium ions, water and oil.

Explain why in the recrystallization of Aspirin the water should

not be heated above 80C.

Aspirin may decompose back into salicylic acid and acetic anhydride when the temperature is too high.

Explain the results obtained when Aspirin and salicylic acid were treated with Ferric chloride solution.

Ferric chloride reacts with phenol to give a purple solution.

Since salicylic acid has a phenol group, it is expected to give a

positive result. If the product gives a purple color with ferric chloride solution, it means that not all of the salicylic acid has been consumed.

Applications:

Another pharmaceutical product derived from salicylic acid is salol (phenyl salicylate), the phenyl ester of salicylic acid. Since phenol cannot be esterified by direct interaction with

salicylic acid, some indirect method must be used. Write

equations for a sequence that might be used to prepare salol from phenol and salicylic acid. Aspirin and salol are both acidic substances. Which is the stronger acid? Which would be more easily hydrolyzed in an alkaline medium? Why?

You have to react phenol with NaOH first. The reaction will produce a salt and water. React the salt with salicylic acid and you will have phenyl salicylate and NaOH as products. The structure of salol is show below:

Aspirin is more acidic than salol because of the stability of its

conjugate base and its COOH functional group. Aspirin will be hydrolyzed easily because it is acidic.

CONCLUSION

To synthesize dye, the phenyldiazonium chloride was produced by reacting aniline with nitrous acid and reacted with naphthol. The reaction involved are diazotization and diazonium-coupling reactions.

To synthesize soap, saponification was employed where fat is hydrolyzed with lye to produce a salt of the fatty acid. The salt

is what we call soap. It is a very effective emulsifying agent

because of its polar and nonpolar ends. However, in the presence of metal ions, precipitate forms. The reaction

mechanism is based on nucleophilic acyl substitution.

To synthesize Aspirin, the reaction called esterification was

done by reacting acetic anhydride with salicylic acid. The reaction mechanism involves five steps.