Beirut reaction

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The Beirut reaction (also Haddadin-Issidorides reaction ) is a name reaction in organic chemistry , which was first described by Haddadin and Issidorides in 1965. Most often the name Beirut reaction is used, which is based on the name of the city of Beirut , the place where the reaction was discovered. Quinoxaline -N, N'-dioxides, i.e. heterocyclic compounds , are synthesized in the reaction . This takes place via a cycloaddition between a benzofuroxan with dienes , enamines , enolates , α , β- unsaturated ketones or 1,3- dinitriles .

Overview reaction

In the Beirut reaction, benzofuroxanes (e.g. benzofuroxan- N- oxide) 1 react with the enolation 2 shown here as an example to form quinoxaline-N, N'-dioxides 3 . A wide variety of organic radicals (for example alkyl , amide , aryl , carboxylate or cyanide groups ) can be used for compound 2 . A tertiary amine can also be used instead of the oxygen atom . As a catalyst usually used a base such. B. triethylamine or ethanolates .

Beirut reaction Overview reaction V1.svg

Reaction mechanism

There are several suggestions as to the reaction mechanism of the Beirut reaction. What they have in common is the first step in which a nucleophilic addition of enolate ion 2 to the electrophilic nitrogen atom of benzofuroxane 1 takes place. Lima and do Amaral assume in the following that protonation takes place first, which leads to the formation of compound 3 . The ring closure to compound 4 takes place in that a connection from the nitrogen of the amine hydroxide group is linked to the carbonyl group . This is followed by β- elimination of water with formation of the quinoxaline-N, N'-dioxide 5 .

Beirut reaction mechanism V2.svg

application

The Beirut reaction is an important way of synthesizing heterocyclic aromatic compounds with amine oxide groups . The reaction products of the Beirut reaction are of particular interest in the pharmaceutical industry, since numerous quinoxaline-N, N'-dioxides have an antiparasitic and antimicrobial effect and can be used to combat tumors . About the reduction can range from quinoxaline-N, N'-dioxides also phenazine - derivatives are prepared as a framework for dyes and antibiotics are used.

Individual evidence

  1. ↑ Makhluf J. Haddadin, Costas H. Issidorides: Enamines with isobenzofuroxan: a novel synthesis of quinoxaline-di-n-oxides . In: Tetrahedron Letters . tape 6 , no. 36 , January 1, 1965, p. 3253-3256 , doi : 10.1016 / S0040-4039 (01) 89222-4 .
  2. ↑ Katritzky, Alan R.,: Advances in Heterocyclic Chemistry . tape 112 . Academic Press, Amsterdam 2015, ISBN 978-0-12-420209-2 , pp. 53-54 .
  3. ↑ a b c d e Zerong Wang: Beirut Reaction . In: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, Inc., Hoboken, NJ, USA 2010, ISBN 978-0-470-63885-9 , pp. 303-306 , doi : 10.1002 / 9780470638859.conrr067 .
  4. ↑ a b c d e L. M. Lima, DN do Amaral: Beirut Reaction and its Application in the Synthesis of Quinoxaline-N, N'-Dioxides Bioactive Compounds . In: Rev. Virtual Quim. 6th edition. No. 5 , 2013, p. 1075-1100 , doi : 10.5935 / 1984-6835.20130079 .
  5. ↑ Entry on phenazine. In: Römpp Online . Georg Thieme Verlag, accessed on December 21, 2018.