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.