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Paracetamol Synthesis: Preparation of Paracetamol (P-Acetomenophen)

This document discusses the synthesis of paracetamol (acetaminophen) through acetylation. It begins by providing background on paracetamol, including its physical properties and uses as a pain reliever and fever reducer. The main reaction involves acetylation of p-aminophenol with acetic anhydride under reflux. The product is recrystallized to purify it, yielding paracetamol crystals with a melting point of 169-170.5°C.

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hussein alnasry
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732 views7 pages

Paracetamol Synthesis: Preparation of Paracetamol (P-Acetomenophen)

This document discusses the synthesis of paracetamol (acetaminophen) through acetylation. It begins by providing background on paracetamol, including its physical properties and uses as a pain reliever and fever reducer. The main reaction involves acetylation of p-aminophenol with acetic anhydride under reflux. The product is recrystallized to purify it, yielding paracetamol crystals with a melting point of 169-170.5°C.

Uploaded by

hussein alnasry
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Download as PDF, TXT or read online on Scribd
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Organic pharmaceutical chemistry III

4th Stage 2nd Course

Paracetamol
synthesis
Pharmacist : Amal saleh

Preparation of paracetamol
(P-acetomenophen)
Acetaminophen is a P- acetamidophenol or it is N-acetyl
Paminophenol or 4-hydroxy acetanilide. M.wt=151.2(gm/mole)

Physical properties: Odorless , white crystals with bitter taste.


M.pt. = 169-172 C0
Solubility: one part(slightly soluble in water and ether) in 70 parts
of water and in 7 parts Of alcohol , soluble in alkali solution(like
NaOH), soluble in boiling water(1:20)
INTRODUCTION
Paracetamol or acetaminophen is a very widely used analgesic and antipyretic.
It is a relatively (toxicity has been observed with very high doses),used for mild
to moderate pain relief, mild analgesic and does not have anti-inflammatory
activity It is often sold in combination with other medications such as in many
cold medications
It used for severe pain such as cancer pain and pain after surgery.
Often taken orally or rectally, but also I. V.
Effect: last 2hrs and 4 hrs.
It is safe at recommended dose. Serious skin rushes may rarely occur and too
high dose can result in liver failure. It appears to be safe in pregnancy and
breastfeeding women.It is on WHO's list of essential medicines, the most
effective and safe medicines needed in a health system.
Paracetamol is available as a generic medication with trade names including
Tylenol and Panadol, among others.

Paracetamol consists of a benzene ring core, substituted by one hydroxy group


and the nitrogen atom of an amide group in the para (1,4) pattern. The amide
group is acetamide (Ethan amide). It is an extensively conjugated system, as
the lone pair on the hydroxyl oxygen, the benzene pi cloud, the nitrogen lone
pair, the p-orbital on the carbonyl carbon, and the lone pair on the carbonyl
oxygen are all conjugated.
- The presence of two activating groups also make the benzene
ring highly reactive toward electrophilic aromatic substitution.

-As the substituents are ortho, para-directing and para with respect
to each other, all positions on the ring are more or less equally
activated.

The conjugation also greatly reduces the basicity of the oxygen's


and the nitrogen, while making the hydroxyl acidic through
delocalization of charge developed on the phenoxide anion.

Acetylation methods:
Acetylation is a chemical reaction in which an acetyl group is
added to a compound in place of a hydrogen atom. An acetyl
group is a chemical functional group composed of a carbonyl
group and a methyl group

The replacement of active hydrogen of compounds belonging to


the class ROH (phenols or alcohols), in addition to compounds of the
category RNH2 and R2NH (i.e., primary- and secondary-amines may
be acetylated directly, whereby the reactive H-atom is specifically
replaced by the acetyl radical acetylation .
Action and uses: it has analgesic and antipyretic actions but has no
anti-inflammatory properties.
Side effects: like that of acetanilide, affect heart and may cause skin
reaction and a jaundice condition (they occur less frequently and less
severity).
in doses used for analgesia ,it is relatively safe drug.
Preparation: It may prepared by reduction of P-nitrophenol in glacial
acetic acid .
acetylation of P-nitrophenol by using acetic anhydride.
Reactivity towards acetylation:
Acetyl chloride > acetic anhydride > acetic acid
The best one: acetic anhydride.
Easily handled, safe and reaction can easily be controlled.

The main reaction of paracetamol

Their characteristic reactions are with nucleophilic reagents, acetic


anhydride reacts with compound containing active hydrogen atom to
form derivatives containing acetyl group
Main mechanism of paracetamol preparation

Physical properties of phenacitin: stable ,white ,glistening


crystals or powder.it is odorless and has a slightly bitter
taste.
Solubility: Very slightly soluble in H2O , soluble in alcohol and
chloroform but slightly soluble in ether, it is sparingly
soluble in boiling H2O it is a neutral compound and will not dissolve
in either acids or alkalis.
Action and uses: it is used widely as an analgesic and antipyretic. the
toxic effects are the same as that of acetaminophen (the active form
of phenacetin in that it is converted in the body to paracetamol)

Toxicity: phenacetin may damage the kidneys when used


in large dose or for long period of time.
The experiment

Procedure:
1) IN A ROUND-BOTTOMED FLASK (100 ML) PLACE1.375 G OF P-
AMINOPHENOL, AND THEN ADD 3.75ML OF DISTILLED WATER.
2) TO THIS MIXTURE, DROP CAREFULLY 1.5 ML OF ACETIC
ANHYDRIDE. ADJUST THE LIEBIG CONDENSER AND HEAT
UNDER REFLUX FOR 20MINUTES AT (115-120 C)
3) AFTER THE SUBSTRATE HAS DISSOLVED, COOL DOWN THE
SOLUTION BY PLACING THE ROUND-BOTTOMED FLASK IN AN
ICE-BATH FOR FEW MINUTES, THEN IN THE FREEZER FOR 10-
15 MINUTES, AND THE CRYSTALS OF PRODUCT SHOULD
APPEAR IN THE FLASK.
4) 4) FILTER THE PRODUCT ON THE BÜCHNER FUNNEL AND WASH
WITH COLD WATER. DRY ON AIR ON PETRI DISH.
Recrystallization:
Dissolve the crude product in 70% (v/v) ethanol and warm
it to 60°C ; add 2 g of powdered animal charcoal
(decolorizing carbon).

Filter and concentrate the filtrate over a water-bath.


Allow it to cool and large monoclinic crystals will separate
out.

The yield of the pure paracetamol (mp 169 170.5°C) is 6.5


g.

THANK YOU!
For Your Attention

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