Makosza reaction

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The Makosza reaction is a name reaction in organic chemistry , which was first introduced in 1983 by Mieczysław Mąkosza and named after him. The reaction is also known as vicarious nucleophilic substitution . The reaction is used to introduce alkyl radicals with functional groups in electrophilic aromatics ( nitroaromatics and heteroaromatics ).

Overview reaction

The Makosza reaction is a substitution reaction and takes place in several reaction steps. This happens with the use of carbanions , which have a leaving group (X = Cl, Br, PhO, PhS etc.) at the nucleophilic center. In addition, the carbanion should have an electron withdrawing group (EWG = Electron Withdrawing Group) (EWG = SO 2 Ph, SO 2 N, CN, CO 2 Et, etc.). Although the nitro group in nitrobenzene normally has a meta- directing effect, in this reaction the ortho or para position is preferred by the second substituent .

Overview reaction of the Makosza reaction

Reaction mechanism

In the proposed reaction mechanism, nitrobenzene 1 is attacked nucleophilically by carbanion 2 . For the sake of simplicity, only the formation of the ortho product is described in the mechanism presented here . By splitting off HX in anion 3 , anion 4 is formed . The protonation of 4 finally gives the product 5 .

Mechanism of the Makosza reaction

In addition, as already mentioned above, the positionally isomeric para version of 5 arises .

history

Until the late 1970s, nucleophilic substitution in aromatic rings was limited to the replacement of halogens or other nucleofugal groups. The nucleophilic exchange of hydrogen was still a special case at that time. In 1983 Makosza published a mechanism according to which the exchange of hydrogen should happen. He established this mechanism by determining the kinetic isotope effect and the influence of the base on the reaction rate. However, it is noticeable that there is another leaving group on the carbanion, which actually gives way instead of the hydrogen atom. Since this leaving group thus acts as a substitute leaving group, the reaction has also been called substitute nucleophilic substitution of hydrogen.

One reaction that Makosza discovered during his research was the following: Nitrobenzene 6 reacts with chloromethylphenyl sulfone 7 with the aid of potassium hydroxide as base and dimethyl sulfoxide as solvent to form a nitrobenzene derivative 8 substituted in the ortho position and a nitrobenzene derivative 9 substituted in the para position .

first Makosza reaction

application

The main application of the Makosza reaction is in the synthesis of heterocyclic rings. This reaction can also be used for the synthesis of natural products. For example, eupolauramine - an azaphenanthrene alkaloid isolated from the bark of an African plant - can be produced.

See also

Individual evidence

  1. ↑ Mąkosza was a chemist in Belarus, where he specialized in organic synthesis and reaction mechanisms.
  2. ↑ Alfred Hassner, Irishi Namboothiri: Organic Synthesis Based on Name Reactions: A Practical Guide to 750 Transformations . Third ed.Elsevier, Amsterdam 2012, ISBN 978-0-08-096630-4 , pp. 298-299 .
  3. ↑ a b c Mieczyslaw Makosza, Tomasz Glinka: Reaction of organic anion. Part 108. On the mechanism of the vicarious nucleophilic substitution of hydrogen in nitroarenes . In: The Journal of Organic Chemistry . tape 48 , no. October 21 , 1983, p. 3860-3861 , doi : 10.1021 / jo00169a067 .
  4. ↑ a b Mieczysław Makosza: Vicarious Nucleophilic Substitution of Hydrogen in the Chemistry of Heterocyclic Compounds . In: Synthesis . tape 1991 , no. 02 , 1991, p. 103-111 , doi : 10.1055 / s-1991-35646 .
  5. ↑ Vicarious Nucleophilic Substitution. Retrieved May 29, 2019 .
  6. ↑ a b c Mieczyslaw Makosza, Jerzy Winiarski: Vicarious nucleophilic substitution of hydrogen . In: Accounts of Chemical Research . tape 20 , no. 8 , 1987, pp. 282-289 , doi : 10.1021 / ar00140a003 .
  7. ↑ Mieczyslaw Mąkosza, Krzysztof Wojciechowski: Application of Vicarious Nucleophilic Substitution in Organic Synthesis . In: Liebig's annals . tape 1997 , no. 9 , 1997, pp. 1805-1816 , doi : 10.1002 / jlac.199719970903 .