Pharmaceutical Organic Chemistry II- Tutorial

Dr. Mehul Patel

Ramanbhai Patel college of Pharmacy, CHARUSAT

1
 Syllabus
Experiments involving laboratory techniques Preparation of compounds
• Benzanilide/Phenyl benzoate/Acetanilide from Aniline/
• Recrystallization Phenol /Aniline by acylation reaction.
• Steam distillation • 2,4,6-Tribromo aniline/Para bromo acetanilide from
AnilineAcetanilide by halogenation (Bromination) reaction.
Determination of following oil values (including • 5-Nitro salicylic acid/Meta di nitro benzene from Salicylic
standardization of reagents) acid / Nitro benzene by nitration reaction.
• Acid value • Benzoic acid from Benzyl chloride by oxidation reaction.

• Saponification value • Benzoic acid/ Salicylic acid from alkyl benzoate/ alkyl
salicylate by hydrolysis reaction.
• Iodine value • 1-Phenyl azo-2-napthol from Aniline by diazotization and
coupling reactions.
• Benzil from Benzoin by oxidation reaction.
• Dibenzal acetone from Benzaldehyde by Claison Schmidt
reaction
• Cinnammic acid from Benzaldehyde by Perkin reaction
• P-Iodo benzoic acid from P-amino benzoic acid
To perform synthesis of p-nitroacetanilide
from acetanilide.
Reference: B.S.Furniss et.al, “VOGEL’s textbook of Practical Organic Chemistry”, 5th edition, Pearson
education, Page No. 948

Sr. No. Name of Chemicals Qty. Taken

1. Acetanilide 6g
2. Glacial Acetic Acid 8 ml
3. Conc. Sulfuric Acid 12 ml + 2ml
4. Conc. Nitric Acid 3 ml

Requirements: Beakers (250ml), Pipette, Measuring cylinder, Conical flask, Funnel, Glass-rod,
Test tube, Filter paper, Hot air oven, Weighing balance, and Ice bath.
Reactions

HNO3+H2SO4
Mechanism
Electrophile

HNO3 + H2SO4 HSO4- NO2+

NHCOCH 3 NHCOCH 3 NHCOCH 3 NHCOCH 3

+
+ +
N+O 2 H H H
NO 2 NO 2 NO 2

NHCOCH 3 NHCOCH 3

+
H
NO 2
HSO4- NO 2
Procedure:

1) First, take 6g of dried Acetanilide and add 8 ml of Glacial Acetic Acid and 12 ml of
Conc. Sulfuric Acid in a 250 ml beaker.
2) The mixture becomes slightly warn and gives clear solution.
3) Place the beaker in an ice bath for cooling until the solution reaches 0ºC.
4) Take a mixture of 3 ml Conc. Nitric Acid and 2 ml of Conc. Sulfuric Acid in a test
tube and cool the solution below 5ºC.
5) Add the cooled solution in the test tubes to the acetanilide solution with continuous
stirring for about 10 minutes while in ice bath. The temperature should not arise
above 8ºC.
6) Remove the mixture from the ice bath and let it sit in room temperature for 10 to
15 minutes.
7) Pour the reaction mixture in ice cold water with continuous stirring.
8) Filter the p-nitroacetanilide precipitates and wash with water.
9) Dry the filtrate and recrystallize with rectified spirit.
10) Weigh the crystals.
Calculation
• Molecular formula of acetanilide: C₈H₉NO
• Relative molecular weight of acetanilide :
• 8 12.0107 + 14.00674 + 9 1.00794 + 15.9994
• = 135.1632 𝑔/𝑚𝑜𝑙
•

• Molecular formula of p-nitroacetanilide: C8H8N2O3

• Relative molecular weight of p-nitroacetanilide:
• 8 12.0107 + 8 1.00974 + 3 15.9994 + 2 14.00674

• = 180.1752 𝑔/𝑚𝑜𝑙
 Calculations
Molecular weight of starting material: X
Molecular weight of product: Y
Weight taken for synthesis: A
Weight of product synthesized: B
• Theoretical yield:
135 gm of acetanilide yield 180gm of p-nitoactanilde
6gm of acetanilide ? (8gm)
• Practical Yield:
Suppose we received 7.2 gm of p-niroacetanilide
• %Practical yield
• 8gm 100%
• 7.2 gm ?
Link for reference
• https://www.youtube.com/watch?v=eUKStJVDdMk
Aim: To perform synthesis of m-
dinitrobenzene from nitrobenzene.
Reference: B.S.Furniss et.al, “VOGEL’s textbook of Practical Organic Chemistry”, 5th edition,
Pearson education, Page No. 855

Sr. Name of Chemicals Qty. Taken

No.
1. Sulphuric acid(concentrated) 6 ml
2. Nitric acid(concentrated) 4 ml
3. Nitrobenzene 3 ml

Glasswares: Iodine flask, Water bath, Pipette, Measuring cylinder, Conical flask, Glass-rod,
Vacuum pump with filtration assembly, Filter paper, Buckner funnel, Hot air oven,
Weighing balance
 Procedure
• 6 ml of concentrated sulphuric acid and 4 ml of concentrated nitric acid were taken in dry beaker
and kept it in ice cold water.
• 3 ml of nitrobenzene slowly added to above nitrating mixture.
• The flask was removed from ice-cold water and allowed the reaction mixture to achieve at room
temperature.
• The reaction mixture was subjected to heat with frequent shaking on boiling water bath for 25-30
minutes.
• The flask was removed from boiling water bath and poured the reaction mixture in ice cold water so
yellow colored m-dinitrobenzene was solidified.
• The product was filtered by suction filtration process and washed the product with ice cold water to
remove acidic impurities.
• The practical yield of the crude m- dinitro benzene was calculated and its melting point was
reported.
Reactions
–
– O O –
O O –
+
+ N O + O
N O + O N
N
H2SO4HNO3+H2SO4H SO
2 4

HNO3 HNO3 + O + O
N N
– –
O O
Aim: To perform synthesis 1-phenyl-azo-2-naphthol from
aniline and β-naphthol.
Reference: B.S.Furniss et.al, “VOGEL’s textbook of Practical Organic Chemistry”, 5th edition,Pearson
education, Page No. 948.
Sr. Name of Chemicals Qty. Taken
No.
1. Aniline 5g (4.9ml)
2. Hydrochloric Acid(concentrated) 16 ml
3. Water 16 ml
4. Sodium Nitrate 4g
5. β -Naphthol 7.8 g
6. Sodium Hydroxide 45 ml

Requirements: Beakers 250ml(03), Pipette, Measuring cylinder, Conical flask, Glass-rod, Vacuum pump with
filtration assembly, Filter paper, Buckner funnel, Hot air oven, Weighing balance
Procedure:
1) First, we have taken three beakers. In the first beaker, 5g (4.9ml, 0.054mol) of aniline has been dissolved in
16ml of Conc. Hydrochloric acid and 16ml water.
2) In 2nd beaker, 4g of sodium nitrate has been dissolved in 20ml of water.
3) In 3rd beaker, 7.8g of β-naphthol has been dissolved in 45ml 10% sodium hydroxide solution (4.5g in 45ml
water).
4) Secondly, all the beakers are kept on ice-bath for 10-15 min. (remember not to freeze it); after the time
interval, the beakers are removed and gradually,the solution of 2nd beaker is added into 1st beaker. Finally,
mix the whole conent into 3rd beaker and stir properly until it thickens and concentrates.
5) After reaching room temperature, the solution will be filtered through vacuum filter assembly. Place regular
filter paper and then place Whatman's filter paper on top of that giving a total of 2 filter media. After
placing these in the buchner funnel, wet the papers and turn on the vacuum filter.
6) Crude acid was purposely remove from the concentrated solution by washing it over the vacuum filter
assembly (indication i.e. appearance of light yellow color filtrate).
7) Lastly, filtrant was collected and kept in oven at 100ᵒ C purposely for drying (almost half-an-hour).
8) Dried product (final product) was collected and weighed it for calculations.
Example to understand mechanism (Phenol)

Exercise: Draw mechanism for ß Napthol

Results Name of the 1-phenyl-azo-2-naphthol
synthesized
compound
Structure
HO

N
N

IUPAC name 1-(phenyldiazenyl)naphthalen-2-ol

Melting point
Theoretical yield
Practical yield
% Practical yield
Application/Uses. 1. It is used to color hydrocarbon solvents, oil, fats, wax, shoes,
floor polishes.
2. Also coloring various foodstuffs, especially curry powder and
chili powder.
3. It is used in formulations of orange colored smoke
Aim: To determine Saponification Value of
the given Fat / Oil.
Reference: Manual of Methods of Analysis of foods (Oils and Fats) By FSSAI - Food Safety and Standards
Authority of India, Govt. of India, 2015 , Page No. 21
Chemicals:
Sr. Name of Chemicals Quantity
No. Taken
1. Oil / Fat 2g
2. 0.5 N HCl In Burette
3. 0.5 N alcoholic KOH solution 25 ml
4. Phenolphthalein 2 - 3 drops

Requirements:
250 ml Conical Flask, Condenser, Water Bath, Burette and Pipette, Measuring Cylinder and Weighing Balance
Theory:

● Definition - The Saponification Value is the miligram of Potassium hydroxide

required to neutralize the free acids and to saponify the ester in 1 gram of Fat / Oil.

● The Saponification value is an index of the average molecular weight of the fatty
acids of glycerides comprising a fat (tri-acyl glycerol). Saponification is the process
of breaking down a neutral fat into glycerol and fatty acid by the treatment with
alkali. The lower the saponification value, the larger the average molecular weight
of tri-acyl glycerols. Saponification value is inversely proportional to average
molecular weight of tri-acyl glycerols.
Procedure:

● About 2 grams of Fat / Oil was weighed accurately in a 250ml Conical flask.

● 25ml of 0.5 N alcoholic KOH solution was added to the Conical flask.

● The reflux condenser was attached and the reaction mixture was refluxed (heated) in the conical flask for
about 1 hour with occasional stirring.

● While the resulting solution was hot, 2 - 3 drops of Phenolphthalein indicator was added to the solution in
the flask.

● The excess of alcoholic KOH solution was then titrated with 0.5 N HCl solution.

● The same procedure was repeated without the sample to perform the Blank experiment.
Reaction
Exercise
Oils Saponification Value
Observations
Burette

Conical Flask

Indicator

Colour Changa

Initial Burette Reading Final Burette Reading Difference

(ml) (ml) (ml)

For Excess KOH S=

remaining

B=
For Blank
Calculation
56.1× 𝐵−𝑆 ×𝑁 𝑜𝑓 𝐻𝐶𝐿
Saponification number= 𝐺𝑟𝑎𝑚 𝑜𝑓 𝑠𝑎𝑚𝑝𝑙𝑒

Where, B=Blank titration value

S= (sample used in titration it’s value)
56.1 is Molecular weight of KOH

Results
The Saponification Value of the given oil / fat was found to be _______________ .
 Aim: To determine the Acid value of given
Fat or Lipid.
Reference: Manual of Methods of Analysis of foods (Oils and Fats) By FSSAI - Food Safety and Standards
Authority of India, Govt. of India, 2015 , Page No. 21
- The acid value is the number that express the milligram the quantity of KOH require to neutralize the free
acids present in the 1 gm of substance.
- the acid value may be overestimated if other acid components are present like amino acid or acid phosphate
- the acid value is a measure of the breakdown of the triacyl glycerol into free fatty acid, which has an adverse
effect on quality of lipid.

Sr. No Name of reagents Quantity Taken

1 Oil or fat 0.25g
2 Ethanol or alcohol 15 ml
3 Phenolphthalein 2-3 drops
4 0.1 N KOH 10ml

Requirements: 250 ml. beaker, burette, pipette, measuring cylinder, conical flask, glass rode, burner.
 Procedure:
1. Take 2.5g of fat or oil in a dried conical flask.
2. Add 15 ml of absolute alcohol and (2-3) drops of phenolphthalein.
3. Heat with shaking in water batch (65%) for 10 min, then cool it.
4. Titrate the solution against 0.1 N KOH until pink colour appears (end point).
5. Calculate acid value (AV) and free fatty acid (%FFA) using following equation.

Observation table:

Initial burette reading (ml) Final burette reading (ml) Difference (ml)

B=
For blank

S=
For excess KOH
remaining
Where, B = vol. of blank reading, S = vol. of sample reading
Reaction:

RCOOH + KOH RCOOK + H2O + KOH

ml of KOH × N × 56
____________________
Acid Value = = mg of KOH
Weight of sample (g)

N = Normality of KOH

% Free fatty acid (FFA) =AV × 0.503

Exercise
Oils Acid Number