University of Puthisastra

Department of Pharmacy

PW of Organic chemistry
Unit 5: Synthesis of Acetophenone by electrophilic
substituents (SE )
 Synthesis of Acetophenone by SE

Objective :
1. Understand of Principle of electrophilic Substitution Reactions
2. Able use SE to synthesis interest compounds as Acetophenone
 Synthesis of Acetophenone by SE
I. Introduction
- Acetophenone was used as hypnotic and anticonvulsant drugs
- Acetophenone are also precursor for other drugs synthesis as Albuterol,
Zolpidem
- Acetophenone is used to impart the fragrance of orange blossoms in
perfumes, soaps, detergents, and lotions.

Zolpidem

Albuterol
 Synthesis of Acetophenone by SE
II. Principle of reaction
➔ Electrophilic substitution reaction is an organic reaction in which
an atom of Chemical compound (usually hydrogen) is replaced by an
electrophile
 Synthesis of Acetophenone by SE
III. Synthesis of Acetophenone
Principle of reaction
Step 1 : create of An acylium ion

Step 2 : form the arenium ion

Step 3 : forming the aryl ketone
 Synthesis of Acetophenone by SE
III. Synthesis of Acetophenone
➔ Chemicals Required :
- Benzene(C6H6): 25 ml
- Aluminium chloride (AlCl3) : 10g
- Acetyl chloride (CH3-COOCl) : 7ml

➔ Procedure of synthesis
- Add AlCl3 = 10g + Benzene = 25ml to three-necked
round bottom
- Pour 7 ml of CH3-COOCl into the dropping funnel and
gentle shaking
- Heating water bath at 500 C +/- 20 C ( 60 min)

Water bath
 Synthesis of Acetophenone by SE
III. Synthesis of Acetophenone
➔ Purify :
- Allow the reaction mixture to cool down to room temperature
- Transfer the reaction mixture into 75 ml chilled water → dark
coloured oil starts floating on the surface
- Stopper the 150 ml flask tightly and shake the contents vigorously
- In case, any solid particle commences to separate at this stage,
add a few drops of conc. HCl to dissolve the same
 Synthesis of Acetophenone by SE
III. Synthesis of Acetophenone
➔ Purify :
- Transfer the mixture to a separating funnel and discard the unwanted
lower aqueous layer
- Washing of the benzene layer with NaOH (2% w/v) solution
- Dry the benzene layer over anhydrous fused CaCl2
- Transfer the residual liquid mixture to a quick-fit distillation assembly
- First fraction around 80°C → Benzene
& 195–202°C → acetophenone
 Synthesis of Acetophenone by SE
III. Synthesis of Acetophenone
➔ Identify :
- Physical Parameters :
● Melting point = 20.5°C
● d15 15 =1.033
● Boiling point = 202°C
● n20D = 1.533
● Solubility :
Water : slightly soluble
EtOH, chloroform, glycerol, fatty oils and ether : freely soluble
- Coloration identify : + H2SO4 → orange
References
- A microscale Approach to organic laboratory techniques , Donald
th
L.Pavia,Gary M. Lampman ,5 edition
- Experimental Organic Chemistry : A Miniscale and Microscale
th
Approach, John C. Gilbert ,Stephen F.Martin ,5 edition
th
- Quantitative Chemical Analysis 7 edition , Daniel C.Harris.
- Introduction to Laboratory techniques , Pavia Kriz ,Lampman Engel ,
1998
rd
- Techniques in Organic Chemistry , 3 edition , Jerry R.Mohrig ,
Christina Noring Hammond Paul F.Schatz