Lab.

Preparation of
Methyl Salicylate
(Oil of Wintergreen)
Ph. Naza Shakir Shareef
Pharmaceutical chemistry 1 Lab
Introduction
• Methyl salicylate is an organic ester that can be isolated by extraction from wintergreen plant

and its the second most common ester of salicylic acid that is used as a drug.

• Methyl salicylate is a colorless yellowish to reddish, viscous liquid with wintergreen odor a

(minty like odor), that can he absorb through the skin.

• It is used in high concentrations as a rubefacient and analgesic in deep heating liniments to

treat joint and muscular pain, in mouth preparations and many other preparations.

• Methyl salicylate can cause a severe allergic reaction, can induce severe stomach pain,

nausea, vomiting, or diarrhea

Uses of methyl salicylate

Food
production

Cosmetics Antiseptic
(aromatizing
ingredient) Listerine
methyl
salicylate

General use
Topical use
(analgesic
cream) (penetrating
oil)
Introduction cont.
• Methyl salicylate could be produced by reacting methanol alcohol with salicylic
acid this process is also referred to as an esterification reaction since a methyl
alcohol and a carboxylic acid in salicylic acid are interacting, this reaction is
reversible and uses an acid as a catalyst (H2SO4).

Heat
Methanol

Salicylic acid
Introduction cont.
The reaction is an equilibrium reaction and particular effort must be made to drive the
reaction to completion:

• Firstly, for the reaction to proceed at an appreciable rate We must add an acid catalyst,
while the addition of the acid gets the reaction going, it cannot drive the equilibrium
towards the products.

• Secondly, this reaction will be driven to completion by the addition of excess methanol.

• Thirdly , alternative methods for driving the reaction to completion include the removal
of water from the reaction.
Introduction cont.
•We used the nucleophilicity of phenolic OH on salicylic acid and the
electrophilicity of acetic acid in the synthesis of acetylsalicylic acid. 

•Salicylic acid additionally has an electrophilic carbon atom as part
 of its carboxyl functional group. Thus, salicylic acid can react with bot
h electrophilic and nucleophilic compounds, 
Safety Precautions:
 Methanol is toxic
 The methyl salicylate that you make in this lab is NOT pure enough
to be taken internally! But you can smell it
 Avoid touching the chemicals.
 Wear your safety goggles.
Chemicals needed
• 1 gm of Salicylic acid
• 7 mL of absolute Methanol
• 0.7 ml of Concentrated H2SO4
• 10 ml of Water
• 10 ml of Ether
• 10% Sodium Bicarbonate
Procedure
1 gm of salicylic acid
7 mL of methanol

0.7 mL of H2SO4

Stir the mixture until the salicylic acid dissolves.

100 ml round bottom flask

Where can we locate the Methanol and H2SO4 in the laboratory ?

And why?
Fume Hood, Concentrated sulfuric acid is very corrosive. And the methanol is a  Flammable liquid  
Procedure cont.
• Reflux the content for 1 hr. under anhydrous
condition at 60-64 C°.
• The reflux will allow the mixture to heat without loss
of components through evaporation. The vertical
condenser returns the evaporated liquids to the
boiling flask.

Why the Temperature set for 60-64 C° ?

It’s the boiling point of Methanol

What is the purpose of refluxing?

To heat a solution in a controlled manner at a
constant temperature without the loss of solvent.
Procedure cont.
• Excess methanol is removed by distillation
(steam bath) or gentle heat with stirring.
• In separatory funnel, 10 ml of water and 10
ml of ether is added to the product.
• Methyl salicylate is soluble in ether layer.
Collect ether layer and discharge aqueous layer
in a separate beaker.
Procedure cont.
• Return ether extract back to separatory funnel, then wash with 10% sodium
bicarbonate (NaHCO3) solution to neutralize the acid and convert the
unreacted Salicylic acid to salt which can be readily dissolved in water.
• Bubbles will come out, so you should open funnel screw after shake.
Check solution with litmus paper to make sure it is neutral. Discharge
aqueous layer in the same beaker

• Collect ether layer and distill or heat gently to remove water and
ethanol.

• Notice nice Wintergreen oil smell of methyl salicylate.

Chemical reaction

2NaHCO3+H2SO4→ Na2SO4+2CO2+2H2O
 Moles Amount
M.wt Density
Name Formula Solubility used/ used/
gm/mol gm/ml
prod prod

Salicylic acid C7H6O3 138 gm/mol   2.5 mg/ml (water)   1 gm

Methyl salicylate C9H8O4 180 gm/mol   3 mg/mL (water)    
Methanol C2H4O2 60 gm/mol 1.05 gm/ml Miscible (water)   7 ml
Sulfuric acid H2SO4 98 gm/mol 1.83gm/ml Violently miscible   0.7 ml
(water)
Homework
Can we synthesis aspirin from methyl
salicylate explain with equation and
procedure?
Thank you