Phenanthridine is a nitrogen heterocyclic compound that is the basis of DNA-binding fluorescent dyes through intercalation. Examples of such dyes are ethidium bromide and propidium iodide. It is an isomer of acridine. Phenanthridine was discovered by Amé Pictet and H. J. Ankersmit in 1891.

Structure

Structurally, the curvature of its aromatic moiety closely matches the shape of an average DNA or RNA base pair, while its length allows for relatively long substituents at the 3- and 8-positions. These positions enable attachment to DNA and RNA, facilitating additional non-covalent interactions with the polynucleotide backbone  [5] [6]. This property makes phenanthridine the basis for DNA-binding fluorescent dyes, such as ethidium bromide and propidium iodide, which intercalate between nucleic acid base pairs. It is also an isomer of acridine [5] [6].

Synthesis

Phenanthridine was prepared by Pictet and Ankersmit by pyrolysis of the condensation product of benzaldehyde and aniline.[3] In the Pictet–Hubert reaction (1899) the compound is formed in a reaction of the 2-aminobiphenyl – formaldehyde adduct (an N-acyl-o-xenylamine) with zinc chloride at elevated temperatures.[4] This traditional method proceeds in low yield and gives various side products (approximately 30-50%). The pyrolysis method involves passing benzylideneaniline through a pumice-filled tube heated to 600–800°C, where rearrangement and decomposition occur. The resulting pyrolysis products are collected and purified through fractional distillation to remove side products such as benzene, benzonitrile, aniline, and biphenyl. The remaining crude phenanthridine can be crystallized as a mercurochloride salt for further isolation.

The second method is the Morgan-Walls reaction that gives a 42% yield of phenanthridine after purification. It involves a cyclodehydration process. This route starts with heating 2-Aminobiphenyl with formic acid to give o-formamidobiphenyl. The intermediate is then treated with phosphorus oxychloride to promote cyclization. Nitrobenzene as a high-boiling solvent can improve the yield by allowing higher reaction temperatures.

Morgan and Walls in 1931 improved the Pictet–Hubert reaction by replacing the metal by phosphorus oxychloride and using nitrobenzene as a reaction solvent.[5] For this reason, the reaction is also called the Morgan–Walls reaction.[6]

Pictet–Hubert reaction

The reaction is similar to the Bischler–Napieralski reaction and the Pictet–Spengler reaction.

References

  1. ^ International Union of Pure and Applied Chemistry (2014). Nomenclature of Organic Chemistry: IUPAC Recommendations and Preferred Names 2013. The Royal Society of Chemistry. p. 212. doi:10.1039/9781849733069. ISBN 978-0-85404-182-4.
  2. ^ Lide, David R. (1998), Handbook of Chemistry and Physics (87 ed.), Boca Raton, FL: CRC Press, pp. 3–460, ISBN 0-8493-0594-2
  3. ^ Pictet, Amé; Ankersmit, H. J. (1891). "Ueber das Phenanthridin". Justus Liebigs Annalen der Chemie. 266 (1–2): 138–153. doi:10.1002/jlac.18912660107.
  4. ^ Pictet, Amé; Hubert, A. (1896). "Ueber eine neue Synthese der Phenanthridinbasen". Berichte der Deutschen Chemischen Gesellschaft. 29 (2): 1182–1189. doi:10.1002/cber.18960290206.
  5. ^ Morgan, Gilbert T.; Walls, Leslie Percy (1931). "CCCXXXV.—Researches in the phenanthridine series. Part I. A new synthesis of phenanthridine homologues and derivatives". J. Chem. Soc.: 2447–2456. doi:10.1039/JR9310002447.
  6. ^ Jie Jack Li, ed. (2004). Name Reactions in Heterocyclic Chemistry. Wiley.
Allikas: http://en.wikipedia.org/wiki/Phenanthridine
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