Chemistry, Reactivity, Method of Synthesis of Acridine.

Chemistry of Acridine

Session Objectives

By the end of this session, students will be able to:

• Discuss chemistry, reactivity, method of synthesis of acridine.


• Carl Grabe and Heinrich Caro first isolated acridine in 1870 from coal tar

• It is an aza derivative of anthracene.

• Nitrogen atom is assigned position 10

• Acridine and its derivatives have applications as chemotherapeutic drugs and dye stuffs.


Pale yellow crystalline solid.

Melting Point: 114 C

Acridines and its derivatives gives fluorescent solution.


Acridine and its homologues are weakly basic. Acridine has a pKa of 5.1 similar to that of pyridine.


The Bernthsen acridine synthesis is the chemical reaction of a diarylamine heated with a carboxylic acid (or acid anhydride) and zinc chloride to form a 9-substituted acridine

Using zinc chloride, one must heat the reaction to 200-270 °C for 24hrs. The use of polyphosphoric acid will give acridine products at a lower temperature, but also with decreased yields.


Reaction with acids: Acridine is a weak base but forms soluble salts with mineral acids.

Electrophilic Substitution:

Bromination gives 2 and 2,7-dibromo products.

Acridine N-oxide undergoes nitration (HNO3/H2SO4 at OC) to produce 9-nitro acridine N-oxide.

Reaction with Nucleophilic reagents:

It undergoes nucleophilic attack at position 9.

The decreased electron density at this position when compared to 1,2,3,4

Reaction of acridine with sodium amide in liquid ammonia gives 9-aminoacridine.

Reaction with oxidising agent:

Acridine is a very stable ring system towards the action of oxidising agents.

It is not easily oxidised but is converted into acridine N-oxide with peracids.

This oxide is a yellow solid. MP: 169 and in ethanol solution gives a green fluorescein.

It is brominated and nitrated at position 9.

Reaction with Reducing agents:  9-substituted acridines can be reduced by

Sodium in ether to corresponding acridanes. 

The benzene ring in acridine is selectively reduced by pd or Rh/C in hydrochloric acid, platinum oxide in trifluoro acetic acid to produce dioctahydro acridine.

Applications of Acridine

Several dyes and drugs feature the acridine skeleton.

Many acridines, such as proflavine, also have antiseptic properties.

Acridine and related derivatives (such as amsacrine) bind to DNA and RNA due to their abilities to intercalate. It has been used in acute lymphoblastic leukemia.

Acridine orange (3,6-dimethylaminoacridine) is a nucleic acid-selective metachromatic stain useful for cell cycle determination.

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