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.

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.

PROPERTIES

 OF ACRIDINE

Pale
yellow crystalline solid.

Melting
Point: 114 C

Acridines
and its derivatives gives fluorescent solution.

Basicity

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

SYNTHESIS OF ACRIDINE

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.

CHEMICAL REACTIONS OF ACRIDINE

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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