Synthesis of Organic

Compounds

Pineda ¤ Tan
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 Organic Synthesis
• A special branch of organic chemistry that
deals with making organic compounds
using organic reactions
• Done when organic compounds are not
readily obtained from commercial sources
(the market)
• Application of the theoretical discussions
on organic reactions in real life
 Dyes
• Were once extracted from plants
(pigments)
• 1854- First dye (mauve) synthesized by
William Perkin while trying to synthesize
quinine
– Advent of azo dyes (synthetic dyes which
come in a wide range of colors), whose
general structure includes an azo group
(N=N) attached to 2 aromatic rings
 Soap
• Plants containing saponins (chemicals that
produce a soap-like lather) were used
before the discovery of soap-making
methods
 Aspirin
• Trade name for acetylsalicylic acid
• Taken to reduce fevers, relieve pain, and
even help prevent heart attacks
• originated from the extract of a willow tree
(was highly acidic & caused irritation to
stomach)
• 1893- Felix Hoffmann synthesized
acetylsalicylic acid or aspirin
 Objectives
• Synthesize an organic compound (duh!) :P
• Apply lessons learned in past experiments to
determine percent recovery and properties of each
compound synthesized
• Understand underlying processes (organic
reactions, reaction pathways and reaction
mechanisms) that led to the production of said
organic compounds
Results and
Discussion

Warning:
Numbers ahead.
Kufufufufu…
@_@
 Dye Synthesis

Two Main Steps:

1. Diazotisation
2. Azo coupling
 Synthesis of 1-Phenylazo-2-
naphthol
Theoretical Yield 2.4 g
Actual Yield 4.52 g Recall:
Stoichiometry
Percent Yield 188.33%

Appearance Clay-like
Color Red-orange
Texture Muddy, waxy
Odor Wax-like
Melting point 87-90°C (131°C)
 Chemical Tests

Test Performed Observations

0.1M NaOH Orange colloid
0.1 M HCl Orange colloid
NH4OH Orange colloid
CH3COOH Orange colloid
1. HCl + NaNO2  HNO2 + NaCl
HCl: 2.48 grams
NaNO2: 0.75 grams
MW of HCl: 36 grams
MW of NaNO2: 69 grams
MW of HNO2: 47 grams
HCl:
2.48g HCl x 1mol HCl x 1mol HNO2 = 0.069mol HNO2
36g HCl 1mol HCl
NaNO2:

0.75g NaNO2 x 1mol NaNO2 x 1mol HNO2 =0.011mol HNO2

69 moles NaNO2 1molNaNO2

Therefore, the limiting reagent is NaNO2.

The maximum yield for HNO2 is:

0.011mol HNO2 x 47g HNO2 = 0.517g HNO2
1mol HNO2
2. C6H5NH2 + HNO2  C6H5N2Cl + 2H2O
Aniline: 0.92 grams
HNO2: 0.517 grams
MW of Aniline: 93g/mol
MW of HNO2: 47g/mol
MW of diazonium salt: 140g/mol
Aniline:

0.92g aniline x 1mol aniline x 1mol salt =0.0099molsalt

93g aniline 1mol aniline
HNO2:
0.517g HNO2 x 1mol HNO2 x 1mol salt = 0.011mol salt
47g HNO2 1mol HNO2

Therefore, the limiting reagent is aniline.

The maximum yield for the diazonium salt is:

0.0099mol salt x 140g salt = 1.386g salt

1mol salt
3. C6H5N2Cl + C10H7OH  C6H5N2C10H6OH + HCl
Diazonium salt: 1.386 grams
Beta-naphthol: 1.4 grams
MW of diazonium salt: 140 grams
MW of beta-naphthol: 144 grams
MW of 1-phenylazo-2-naphthol: 248 grams
Diazonium salt:
1.386gsalt x 1molsalt x 1moldye = 0.0099moldye
40gsalt 1molsalt
Beta-naphthol:

1.4g B-naphthol x 1mol B-naphthol x 1mol dye = 0.0097mol dye

144g B-naphthol 1mol B-naphthol

Therefore, the limiting reagent is Beta-naphthol.

The maximum theoretical yield of the azo dye is:

0.0097mol dye x 248g dye = 2.4g dye
1mol dye
%yield = 4.52g x 100 = 54%
2.4g
 1-Phenylazo-2-naphthol (Sudan I)
• a powdered substance with an orange-red
appearance
• used to colour waxes, oils, petrol, solvents
and polishes.
• Has been classified as category 3
carcinogens (not classifiable as to its
carcinogenicity to humans) by the
International Agency for Research on
Cancer.
Guide Questions
 What reactions are involved in the
synthesis of 1-phenylazo-2-naphthol?
• 1-phenylazo-2-naphthol is synthesized in a two-step
reaction: formation of a diazo compound and a
coupling reaction. The first step of this synthesis
involves transforming the aniline derivative (aniline
– benzene containing an amino group) into a
diazonium salt with sodium nitrite (NaNO2) under
acidic conditions. The next step of the reaction
involves a “coupling” reaction with either an amino-
containing aromatic ring or an alcohol-containing
aromatic ring (phenol – aromatic ring with a
hydroxyl group).
• The second step is azo coupling, which
involves the electron-rich coupling
component, a phenol or an aromatic
amine. It reacts with the diazonium salt,
which acts as an electrophile, to form a
stable azo dye through an electrophilic
aromatic substitution. The -OH or -NH2
group direct the aryl diazonium ion to the
para position, but if that position is
occupied, the ion attaches to the ortho
position.
 Write the reaction pathway and mechanism
for the synthesis of 1-phenylazo-2-naphthol.

Diazotisation

NaNO2 + HCl  HNO2 + NaCl

+ Cl-
Azo Coupling
Why should the temperature of the reaction
mixture be kept below 5°C?
• The temperature should be kept below
5°C because in higher temperature,
phenyldiazonium ion reacts with water and
decomposes to phenol, nitrogen gas, and
hydrogen leading to discrepancies and
unwanted products
 Explain the principle behind the use of
starch iodide paste in detecting excess
nitrous acid.
• The starch iodide paste is used to detect
oxidizing agents such as metal cations and acids
such as nitrous acid. Nitrous acid is a Lewis acid
and therefore a proton donor. It is reduced in a
reaction and acts as an oxidizing agent. The loss
of one H+ atom causes the N atom to have a
positive charge because the electrons are
delocalized towards the more electronegative O
atom. In order to become neutral, it takes
electrons from the iodine forming iodide ions
which interact to form molecules of I2 and
reducing the NO2 molecule.
• When elemental iodine (I2) and iodide ions are
present, an acid-base reaction occurs wherein I2
acts as a Lewis acid and I- acts as a Lewis base
forming a trioiodide ion, I3-. This is a linear
molecule which reacts with starch to form the
blue spot observed on the paper.
• Starch iodide paper determines whether the
reaction is complete by testing for the
presence of nitrous acid (HNO2). A positive
test is shown by the change of the colorless
indicator paper to a deep blueblack color.
Once the reactions are complete, free NO2 in
the reaction mixture can be protonated to
form nitrous acid. Thus a positive test from
starch-iodide paper signals the reaction is
complete.
Why is the rate of coupling of phenyldiazonium ion
with β-naphthol dependent upon the pH of the
reaction mixture?
• The last step of the reaction mechanism
involves protonation which is dependent
on the acidity of the reaction mixture.
Greater acidity or lower pH means a
higher concentration of H+ ions is present.
Therefore, a faster reaction rate would
exist.
 Application:
• 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 steps only).
 Congo Red

Diazotisation
Azo Coupling

Congo
Red
• What is the probable site of protonations in
the other substances (which is largely
responsible for the blue color)? Write two
resonance structures for the second
protonated substance that will show the
nature of the chromophore responsible for
the blue color.
Conclusion & Recommendation
• Synthesizong dye requires 2 steps: diazotization
and azo coupling.
• Aniline is first reacted with nitrous acid, then with
naphthol. The procedures must be done under
the hood. The compound must always be
handled with care, and skin contact with the
chemicals must be avoided since nitroanilines
and naphthols are highly toxic, and sodium
hydroxide and hydrochloric acid are corrosive,
and sodium nitrite is a toxic oxidizer, and azo
dyes are irritants.
• Also, gloves must be worn throughout the
experiment.
• Diazonium salts must be kept cold and in
liquid form since they are explosive in solid
form.
 Soap Synthesis

Two Main Steps:

1. Saponification
2. Salting out
 Synthesis of Soap
Theoretical Yield 5.28 g
Actual Yield 12.09 g
Percent Yield 228.98%

Appearance Solid mass

Color White
Texture chunky, powdery, rough
Odor Odorless
Melting point 75-85°C
 Chemical Tests
pH (litmus paper) basic
Calcium chloride white cloudy solution
Magnesium chloride white solution with white
precipitate
Ferric chloride orange solution with yellow
precipitate
Solubility soluble in methylene chloride
Mineral oil miscible
Oil + water immiscible
C51H9806 + 3NaOH  C3H8O3+ Na3C48H93O6
Fat: 5 grams
NaOH: 2.5 grams
MW of fat: 806g/mol
MW of NaOH: 40g/mol
MW of Glycerol: 92g/mol
MW of soap: 278g/mol
Fat:
5g fat x 1mol fat x 3mol soap = 0.019mol soap
806 g fat 1molfat
NaOH:
2.5g NaOH x 1mol NaOH x 3mol soap = 0.062mol soap
40g NaOH 3mol NaOH
Therefore, the limiting reagent is fat.
The maximum yield or theoretical yield for
soap is:
0.019mol soap x 278g soap = 5.28g soap
1molsoap
%yield = 12.09g x 100 = 228.98%
5.28g
 Soap
• sodium or potassium salt of long chain
fatty acids produced by saponification or
the base catalyzed hydrolysis of
triglycerides, fats or oils.
• triglyceride is reacted with a strong base,
such as sodium or potassium hydroxide to
produce glycerol and fatty acid salts (w/c
is called the soap)
 Fatty Acid
• Straight-chain monocarboxylic acids w/c range
in size from 10-20 carbons and most often have
an even number of carbon atoms including the
carboxyl group carbon
• Carbon-carbon bonds in saturated fatty acids
are all single bonds, while unsaturated fatty
acids have one or more carbon-carbon double
bonds in their chains
• Seldom found as free molecules in nature but
are most often a part of a larger molecule called
a triglyceride
 Triglyceride
• A large molecule consisting of a three-
membered carbon chain (glycerol
backbone) with a fatty acid bonded to
each of the three carbon atoms in the
glycerol backbone
• In the saponification process, the ester
linkage (bond between the fatty acid and
the glycerol backbone) is broken to form
glycerol and soap.
 Saponification
• Saponification is the hydrolysis of an ester
under basic conditions to form an alcohol
and the salt of a carboxylic acid.
Saponification is commonly used to refer
to the reaction of a metallic alkali (base)
with a fat or oil to form soap. Saponifiable
substances are those that can be
converted into soap.
 Salting Out
• After saponification, process of adding salt
into soap solution in order to precipitate
soap from water
• Makes use of Na+ and Cl- ions that bind to
the polar water molecules
Guide Questions
What is the reaction involved in the
synthesis of soap?

• The two reactions involved in the

synthesis of salt are saponification and
salting-out
• CH2-OOC-R -CH-OOC-R-CH2-OOC-R
(fat) + 3NaOH →CH2-OH -CH-OH-CH2-
OH+ 3R-CO2-Na
Write the reaction pathway and mechanism
for the synthesis of soap.
 Why was the dilute solution poured in a
solution of sodium chloride in water?
• Pouring the diluted solution into brine water is
a part of the process of soap-making called
salting out. The salt increases the density of
the solution and decreases the solubility of
the soap, a monoelectrolyte, by providing
Na+ and Cl- ions that bind to the polar water
molecules, and help separate the water from
the soap. Thus, soap is precipitated/forced
out from the water, glycerol and unreacted
NaOH. The final product will be the sodium
salt of the fatty acid.
 Explain the result obtained when the dilute
soap solution is treated with calcium
chloride, magnesium chloride and ferric
chloride solutions.
• Soap is normally made from sodium/ potassium
salts which are soluble in water. When the
carboxylic anions from these salts combine with
certain ions (such as calcium, magnesium and
iron ions) which are found in hard water, soap
molecules will form an insoluble precipitate know
as soap scum.
 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
• When grease or oil with nonpolar
hydrocarbons are mixed with a soap and water
solution, the soap molecules work as a bridge
between polar water molecules and nonpolar
oil molecules. Since soap molecules have both
polar and nonpolar properties, it acts as an
emulsifier, letting the oil disperse into the
water.
• This means that while oil, which attracts
dirt, doesn't naturally mix with water, soap
can suspend oil/dirt in such a way that it
can be removed. The soap will form
micelles and trap the fats within the
micelle. Since the micelle is soluble in
water, it can easily be washed away.
 Application
• 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.
• Soap would not be a good choice to be an
emulsifying agent in acidic water, since the
carboxylate group of soap protonates in
acidic water. This forms an uncharged,
insoluble molecule, which is not surface-
active. The protonated soap molecule
does not have a charged head, so it is no
longer soluble in water. The soap
molecules precipitate out forming a cloudy
mixture, which, like hard water, leads to
the formation of a scum.
• As salts of weak acids, they are converted
by mineral acids into free fatty acids which
do not have any cleaning ability:
CH3(CH2)16CO2-Na+ + HCl CH3(CH2)16CO2H +
Na+ + Cl-
• Because of these problems, most of the
“cleaning” that is now done is done with
synthetic detergents that can be designed to
avoid the problems that are present with “soap”.
Conclusion & Recommendation
• Soap synthesis requires 2 steps:
saponification and salting out.
• Saponification was employed when fat is
hydrolyzed with lye to produce a salt of the
fatty acid, which is the soap
• Soap is a very effective emulsifying agent
because of its polar and nonpolar ends
• However, soap forms precipitates in the
presence of metal ions.
• The reaction mechanism is based on
nucleophilic acyl substitution.
• Excess sodium hydroxide must be avoided
since it can cause irritation and injuries
upon contacts with the skin.
• Meanwhile, too little sodium hydroxide
results in a brittle soap.
• Also, excess ethanol must be placed in
appropriate labeled waste container in
hood after use since it is flammable, toxic,
and may cause headaches upon
prolonged exposure to its vapors.
 Aspirin Synthesis

• Esterification
 Synthesis of Aspirin
Theoretical Yield 2.52 g
Actual Yield 0.64 g
Percent Yield 25.4%

Appearance Crystalline
Color White
Texture Fine
Odor Vinegar-like
Melting point 96-115°C (135 °C )
 Chemical Tests

Test Performed Observations

Aspirin + EtOH + Violet solution
FeCl3
Salicylic acid + Violet solution
EtOH + FeCl3
C7H6O3 + C4H6O3  C9H8O4 + C2H4O2
Salicylic acid: 2 grams
Acetic anhydride: 5.41grams
MW of salicylic acid: 138g/mol
MW of acetic anhydride: 102g/mol
MW of aspirin: 180g/mol
MW of acetic acid: 60g/mol
Salicylic acid:
2g acid x 1mol acid x 1mol aspirin = 0.014mol
aspirin
138g acid 1mol acid
Acetic anhydride:
5.41g anhydride x 1mol anhydride x 1mol aspirin = 0.053mol aspirin
102g anyhydride 1mol anhydride

Therefore, the salicylic acid is the limiting

reagent.
The maximum yield or theoretical yield for
aspirin is:
0.014mol aspirin x 180g aspirin = 2.52g aspirin
1mol aspirin
% yield = 0.64g x 100 = 25.4%
2.52g
 Esterification
• the acid catalyzed reaction of a carboxyl (-
COOH) group and a hydroxyl (-OH) group
of an alcohol or phenol  to form a
carboxylate ester.
Guide Questions
What is the reaction involved in the
synthesis of Aspirin?
• Esterification, which involves addition of
the hydroxyl group of the alcohol to the
electron deficient carbonyl carbon of the
acid. The reaction rate is increased by the
addition of small quantities of mineral
acids such as sulfuric or phosphoric acid.
• Acetic anhydride reacts with the phenolic
hydroxyl group of the salicylic acid to
produce acetylsalicylic acid and acetic
acid.
 Write the reaction pathway and
mechanism for the synthesis of Aspirin
• Reaction Pathway:
Reaction Mechanism
 Explain why in the recrystallization of
Aspirin the water should not be
heated above 80°C?
• The solution contained volatile alcohols
which may evaporate when heated above
80°C and may render the recrystallization
less efficient
 Explain the results obtained when
Aspirin and salicylic acid were
treated with FeCl3 solution.
• The addition of ferric chloride to salicylic
acid produces a specific color caused by
the reaction of salicylic acid with aqueous
ferric (Fe(H20)6+3) ion. The oxygen atoms
of the acid group –COOH, and of the -OH
group on the salicylic acid together can
form a complex with (Fe(H20)6+3).
• That complex has an intense violet color.
In aspirin, the –OH group of salicylic acid
has been replaced by a O-COCH3 group
which prevents the second bond from
being formed. The resulting complex with
aspirin shows only a slight yellow color,
not very different from that of
(Fe(H20)6+3) itself. The violet color of
the salicylic acid complex will form the
basis for a colorimetric determination of
the purity of aspirin.
 Application
• 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.
• Phenyl salicylate, C6H4(OH)-C-02C6H5, or
salol, is obtained by heating salicylic acid,
phenol and phosphorus oxychloride to
120-125° C.; or by heating salicyl
metaphosphoric acid and phenol to 140-
150° C. It crystallizes in rhombic plates
which melt at 42° C. and boil at 172° C.
(12 mm.). Its sodium salt is transformed
into the isomeric C6H4(0C6H5) CO2 Na
when heated to 300°.
 Application
• Aspirin and salol are both acidic
substances. Which is the stronger acid?
Which would be more easily hydrolyzed in
an alkaline medium? Why?
• Aspirin is a stronger acid due to the presence
of carboxylic acid which has a reciprocal
hydrogen bonding and highly positive
hydrogen. Salol, on the other hand, is less
acidic because it has a phenyl group that
reduces acidity. Aspirin’s conjugate base is
also mor stable compared to salol. It is easily
hydrolyzed in alkaline medium because of
high ionization constant derived from its
acidic properties. The H+ in aspirin is easily
ionized due to the presence of O, which is
electronegative) in the carboxyl group.
Conclusion & Recommendation
• Aspirin synthesis employs esterification.
• Esterification was done by reacting acetic
anhydride with salicylic acid.
• The salicylic acid and aspirin are not
hazardous, but may cause irritation to the
skin and eyes upon contact
• An excess of these compounds may be
disposed of in the sink
• The acetic anhydride and phosphoric acid
must be used under the hood since they
may cause bad burns
• Gloves and safety goggles must always be
worn when using these chemicals.
• Excess chemicals must be disposed of in
the plastic tub of water. This will convert
the acetic anhydride to vinegar and dilute
the phosphoric acid.
• If there are spills, wipe them up with a wet
paper towel and throw the towel in the
trash.
Thank you for
listening!