• 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.