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Acridine, C13H9N, is an organic compound and a nitrogen heterocycle. Acridine is also used to describe compounds containing the C13N tricycle.
Acridine is structurally related to anthracene with one of the central CH groups is replaced by nitrogen. Acridine, a colorless solid, was first isolated from coal tar. It is a raw material used for the production of dyes and some valuable drugs. Many acridines, such as proflavine, also have antiseptic properties. Acridine and related derivatives bind to DNA and RNA due to their abilities to intercalate. Acridine orange (3,6-dimethylaminoacridine) is a nucleic acid-selective metachromatic stain useful for cell cycle determination. Acridarsine is formally derived from acridine by replacing the nitrogen atom with one of arsenic, and acridophosphine by replacing it with one of phosphorus.
History
Acridine was first isolated in 1871 by
Carl Gräbe and
Heinrich Caro.
Sources
Acridine occurs naturally in
coal tar. It is separated from coal tar by extracting with dilute
sulfuric acid; addition of
potassium dichromate to this solution
precipitates acridine bichromate. The bichromate is
decomposed using
ammonia.
Many synthetic processes are known for the production of acridine and its derivatives. A. Bernthsen condensed diphenylamine with carboxylic acids, in the presence of zinc chloride in the Bernthsen acridine synthesis. With formic acid as the carboxylic acid the reaction yields acridine itself, and with the higher homologues the derivatives substituted at the meso carbon atom are generated.
Other older methods for the organic synthesis of acridines include condensing diphenylamine with chloroform in the presence of aluminium chloride, by passing the vapours of orthoaminodiphenylmethane over heated litharge, by heating salicylic aldehyde with aniline and zinc chloride to 260 °C or by distilling acridone (9-position a carbonyl group) over zinc dust.
A general method for acridine synthesis is the cyclisation of N-phenylanthranilic acid or 2-(phenylamino)benzoic acid with phosphoric acid.
A classic method for the synthesis of acridones is the Lehmstedt-Tanasescu reaction.
Physical properties
Acridine and its homologues are stable compounds of weakly basic character. Acridine has a
pKa of 5.6, which is similar to that of
pyridine. It also shares properties with
quinoline which is the single fused homologue. Acridine crystallizes in needles which melt at 110 °C. It is characterized by its irritating action on the skin, and by the blue
fluorescence shown by solutions of its salts.
Chemical properties
Acridine combines readily with
alkyl iodides to form alkyl acridinium iodides, which are readily transformed by the action of alkaline
potassium ferricyanide to
N-alkyl acridones. On oxidation with
potassium permanganate it yields
acridinic acid C
9H
5N(COOH)
2 or quinoline-1,2-dicarboxylic acid. Acridine is easily
oxidized by
peroxymonosulfuric acid to the acridine
amine oxide. The carbon 9-position of acridine is activated for
addition reactions. The compound is reduced to the 9,10-dehydroacridine and reaction with
potassium cyanide gives the 9-cyano-9,10-dehydro derivative.
Numerous derivatives of acridine are known and may be prepared by methods analogous to those used for the formation of the parent base. 9-Phenylacridine is the parent base of chrysaniline or 3,6-diamino-9-phenylacridine, which is the chief constituent of the dyestuff phosphine (not to be confused with phosphine gas), a by-product in the manufacture of rosaniline.
Chrysaniline forms red-coloured salts, which dye silk and wool a fine yellow; and the solutions of the salts are characterized by their fine yellowish-green fluorescence. Chrysaniline was synthesized by O. Fischer and G. Koerner by condensing ortho-nitrobenzaldehyde with aniline, the resulting ortho-nitro-para-diamino-triphenylmethane being reduced to the corresponding orthoamino compound, which on oxidation yields chrysaniline.
Benzoflavin, an isomer of chrysaniline, is also a dye-stuff, and has been prepared by K. Oehler from meta-phenylenediamine and benzaldehyde. These substances condense to form tetra-aminotriphenylmethane, which, on heating with acids, loses ammonia and yields 3,6-diamino-9,10-dihydrophenylacridine, from which benzoflavin is obtained by oxidation. It is a yellow powder, soluble in hot water.
Cancer link
Acridine is a known human
carcinogen. It causes frameshift mutations in incorporating into the
DNA, and doing so creating an additional base on the opposite strand. If that mutation occurs in a coding sequence, it almost always leads to inactivation of the
protein it encoded.
References
Synthesis of Acridine-based DNA Bis-intercalating Agents Gerard P. Moloney, David P. Kelly, P. Mack Molecules 2001, 6, 230-243 open source
External links
Synthesis of acridone in Organic Syntheses 19:6; Coll. Vol. 2:15 from o-chlorobenzoic acid and aniline in a Goldberg reaction.
Synthesis of 9-aminoacridine in Organic Syntheses 22:5; Coll. Vol. 3:53. from N-phenylanthranilic acid.
Category:Acridines
