The document describes the synthesis of aspirin from salicylic acid. Salicylic acid undergoes acetylation in the presence of acetyl chloride and pyridine as a base. This results in an esterification reaction where the hydroxyl group of salicylic acid is acetylated, forming aspirin. The reaction mechanism and experimental procedure for the synthesis are provided. The properties and uses of aspirin as an analgesic, antipyretic and anti-inflammatory drug are also summarized.

1. Domain-Drug design and process chemistry
Submitted by – Anurag Gupta
Roll no-1902020500025

2. Contents
 Acetylation
 Aspirin
 Synthesis of Aspirin
 Calculation
 Observations
 Uses
 Reference

3. Acetylation
 Introduction of an acetyl group (Acetoxy group,CH3C=O group) into an organic
chemical compound is known as Acetylation
 Acetylation is a chemical reaction in which a hydrogen atom is substituted for an
acetyl group (CH3C=O group) in a compound. The products formed in
acetylation reactions typically have an acetoxy functional group.
 When the hydrogen atom belonging to an alcohol group replaced with an acetyl
group in an acetylation reaction, an ester is formed as the product
E.g.

4. O-Acetylation & N-Acetylation
E.g.
Amines
N-acetylation Amide
E.g.
Alcohol/phenol
O-acetylation
Ester

5. Aspirin
 Aspirin is also commonly known by the name Acetyl salicylic acid .
 It’s IUPAC name is : 2-Acetoxy benzoic acid.
 It has the ability to reduce fever (an antipyretic), to reduce pain (an analgesic), and to
reduce swelling, soreness, and redness (an anti-inflammatory agent).
 Aspirin is also used long-term to help prevent further heart attacks, ischemic strokes,
and blood clots in people at high risk.
2-Acetoxy benzoic acid

6. Synthesis of Aspirin
The acetylation of salicylic acid occurs in an basic medium. Here, the basic
medium (usually pyridine) aids in the detachment of the chloride from the acetyl
chloride. This chloride goes on to associate with the proton liberated by the
phenolic OH group (hydroxy group) of the salicylic acid molecule, resulting in
the formation of hydrochloric acid. The mechanism of the acetylation reaction
undergone by salicylic acid to afford aspirin and hydrochloric acid as the product .
It can be noted that acetylsalicylic acid is commonly known as aspirin.
Salicylic acid Acetyl chloride
Aspirin

7. Reaction Mechanism
Salicylic acid Acetyl chloride
Aspirin
Pyridine

8. Chemicals required
Requirements
Apparatus required  Conical flask
 Beaker
 Stirring rod
 Pipette
 Water bath
 Oven
 Salicylic acid
 Pyridine
 Acetyl chloride
 Water
 Acetic acid

9. Procedure for synthesis of aspirin
 Dissolve 5 gm of salicylic acid in 3.5 mL of dry pyridine contained in a conical flask.
 Then without delay (since this solution if allowed to stand tends to become a semisolid mass) run
in 3.75 mL of acetyl chloride adding about 1 mL of it at a time & shake the mixture continuously
during the addition.
 Maintain the temperature b/w 50-600C throughout the addition.
 Heat the mixture on a boiling water bath 5-10 min.
 Then after cooling pour it into a beaker containing cold water (approx. 150) with stirring
continuously.
 The crude acetyl salicylic acid (ASPIRIN) either solidifies at once or separates as oil, which
rapidly crystallizes as the stirring proceeds.

10.  Crude product collected was dissolved in aqueous acetic acid in a 100mL conical flask. Warmed.
 Approx 30mL of hot distilled water is added to the solution. If solid separates, warm till solid
dissolved completely.
 Solution allowed to cool down.
 The dried crystal is weighed together with the filter paper and watch glass. Weight is recorded.
 A clean and dry watch glass is measured together with a filter paper and the weight is measured
and recorded.
Recrystallisation Of Aspirin

11. Calculations
Step-1: Find the limiting agent-
Start with the balanced chemical reaction-
C7H6O3+ C2H3OCl → C9H8O4 + HCl
Step-2: Calculate the molar mass-
Molar mass of 1 mole of salicylic acid = 138.121 g/mol
Molar mass of 1 mole of acetyl chloride = 78.49 g/mol
Step-3: Convert from grams to moles-
Salicyclic acid = 5g/138.12 g/mol
= 0.036 mol
Acetyl chloride = 3.75g/78.49 g/mol
= 0.047mol
Step-4: Find the ratio of your reaction-
Reaction-your reaction, Ideal reaction
Divide the moles of 1 reactant with other= 0.047/0.036
= 1.3

12. Step-5. Find ideal ratio of reactant-
C7H6O3+ C2H3OCl → C9H8O4 + HCl = 1
Step-6. Compare the above two ratio to find the limiting agent-
Actual reactant 1.3 > 1 ideal
Reactant 1 is in excess salicylic acid , So limiting agent is acetyl chloride
Step-7. Calculating theoratical yield-
Ratio of product/limiting agent = aspirin/acetyl chloride
1 mole of Acetyl chloride is forms 1mole of aspirin.
Therefore,0.047 mole of acetyl chloride forms 0.047 mole of aspirin.
Moles = weight / molecular weight
Weight = moles × molecular weight
=0.047 ×180.158 = 8.46g
Theoratical yield =8.46 g
Practical yield =7.6 g
%yield = practical yield / theoratical yield ×100
= 7.6/8.46 ×100
% yield = 89.83%

13. Observations
1. Melting Point :
Melting point of aspirin = 1470C
2. Rf Value:
A B
2cm
Solvent run
3.5cm
B - Aspirin
A – Salicylic acid
Rf = Distance moved by analyte /
Distance moved by solvent front.
Rf= 2.0/3.5
Rf= 0.57
Mobile Phase
{Hexane : Acetone = 70:30}

14. 3. Nature: 4. Physical State: 5. : Aromatic/Aliphatic
Acidic White crystal Aromatic
(Sooty flame)

15. Computational Parameter
S.No. Parameter Remark
1 Chemical Structure
2 IUPAC Name 2-acetoxybenzoic acid
3 Molecular Formula C9H8O4
4 Molecular Weight 180.16
5 Melting Point 159.410C
6 LogP & CLogP 1.21 And 1.0235
7 Polar Surface Area (tPSA) 63.6
8 Elemental Analysis C, 60.00; H, 4.48; O, 35.52
9 Mass Spectra (m/z) 180.04 (100.0%), 181.05 (10.0%), 182.05 (1.3%)

16. S.No. Parameter Remark
1 Physical State White or almost white, crystalline powder or colorless crystals
2 Color White or colorless
3 Odor Vinegar odor
4 Solubility Freely soluble in alcohol; soluble in chloroform and in ether;
sparingly soluble in absolute ether; slightly soluble in water.
5 Nature Acidic
6 Saturation/Unsaturation Saturated
7 Aliphatic/Aromatic Aromatic
8 % Yield 89.83
9 M.P. (Determined) 147 ºC
10 Rf Value 0.57
Practical Parameter

17. Uses of Aspirin
 To reduce fever(antipyretic).
 To relieve mild to moderate pain from headaches
 To relieve pain from menstrual periods, muscles aches.
 Aspirin does help the heart by thinning the blood and preventing clots
from developing.
 Aspirin is a non-steroidal anti-inflammatory drugs,work as anti-
inflammatory.

18. References
 Vogel’s text book of Practical Organic Chemistry Page No. 1290.
 Ashutosh kar,”advanced practical medicinal chemistry", third edition, 'new age
international (p)limited ,publishers', page no-79-81.
 Practical Organic Chemistry by Frederick George Mann and Bernard Charles
Saunders Published by Longan Inc., Fourth Edition; Page No. 110.
 https://labmonk.com/synthesis-of-aspirin-from-salicylic-acid-using-acetic-
anhydride.
 PubChem Aspirin compound summary accessed 07/05/2020
 Vogel’s text book of Practical Organic Chemistry, Page No. 1290.
 Practical Organic Chemistry by Frederick George Mann and Bernard Charles
Saunders Published by Longan Inc., Fourth Edition; Page No. 110.