Friedel-Crafts acylation

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The Friedel-Crafts acylation is a name reaction in organic chemistry and named after Charles Friedel and James Mason Crafts . In the reaction, aromatics are Lewis acid - catalysis usually with carboxylic acid halides reacted to an acyl moiety ( acylation ) in an aromatic system to introduce. A ketone is obtained as a valuable substance for the reaction . For the Friedel-Crafts acylation, a strong Lewis acid is usually selected (e.g. FeCl 3 , BF 3 or AlCl 3 ), which is used in at least stoichiometric amounts. Friedel-Crafts acylation is an electrophilic aromatic substitution.

Overview of Friedel-Crafts acylation

The acylation can also take place intramolecularly , for example in the synthesis of 1-indanone, a bicyclic ketone:

Intramolecular Friedel-Crafts acylation

There are also embodiments of Friedel-Crafts acylation in which smaller amounts of catalyst are used or the catalyst can be dispensed with entirely. As early as 1955, Vossius described major developments in Friedel-Crafts acylation.

Reaction mechanism

The mechanism is explained in the following section using the reaction of a carboxylic acid chloride with benzene. The Friedel-Crafts acylation is initiated by the Lewis acid coordinating to the carbonyl oxygen of the carboxylic acid chloride 1 and thereby further positiveizing the carbonyl carbon ( 2 ). However, the Lewis acid can also coordinate to the chlorine and trigger the same effect ( 3 ). An acylium cation 4 can then be formed, which attacks the benzene in an electrophilic aromatic substitution and removes the aromatic character. The extent to which the complex of acyl halide Lewis acid 2 or a (mesomeric stabilized) acylium cation 4 is the active agent depends on the substrate, the acyl derivative and the solvent. After the release of a proton, the preliminary end product 7 rearomatizes . The Lewis acid is still coordinated to the carbonyl oxygen. The hydrolysis is to be seen in the last step as a cleaning step and releases the ketone 8 . As a rule, the aromatic compounds themselves serve as solvents for the reaction. However, nitrobenzene , nitromethane or, at low temperatures, dichloromethane are also used.

Mechanism of Friedel-Crafts acylation

Benzene derivatives

Due to the often high steric requirements of the acyl halide-Lewis acid complex, Friedel-Crafts acylation has a high regioselectivity , which leads to the para product when monosubstituted benzene derivatives are reacted. Deactivating substituted aromatics are not acylated according to Friedel-Crafts . Accordingly, multiple acylations are not to be expected in this reaction. These properties make the Friedel-Crafts acylation synthetically valuable compared to the Friedel-Crafts alkylation .

variants

The importance of the reaction is made even greater by the fact that carboxylic anhydrides and carboxylic acids in polyphosphoric acid are also suitable acylating agents. The sequence of Friedel-Crafts acylation and Wolff-Kishner reaction or Clemmensen reduction also makes alkyl-substituted aromatics synthetically accessible. The Gattermann-Koch synthesis is a special case of the reaction .

Recent developments

There are newer versions which the starting material for use of halogen-containing Lewis acids or proton acids refrain and allow the reaction in contact with different solids. The use of zinc oxide was found to be particularly advantageous . With both activated and (weakly) deactivated aromatics such as chlorobenzene , high conversions and yields could be achieved in many cases under mild reaction conditions (room temperature) and short reaction times (a few minutes). The reaction was carried out without solvents. The zinc oxide, which can be used substoichiometrically , could be recovered and used several times. An aqueous work-up was not necessary. A simple non-protic extract was sufficient to achieve high product purity in most cases without further purification. The mechanism has not been investigated. It is conceivable that zinc chloride is formed as a Lewis acid as an intermediate , but the reaction also takes place on graphite instead of the metal oxide. With carboxylic acid anhydrides instead of chlorides the reaction failed. A number of other metal oxides, including aluminum oxide , were found to be significantly inferior or unusable. Good results have been achieved with iron (III) oxide and iron (III) sulfate .

In hexafluoroisopropanol as a solvent, the reaction of electron-rich aromatics takes place at 25 ° C without the need for further additives.

See also

Web links

Individual evidence

  1. ^ A b Siegfried Hauptmann : Organic chemistry . 2nd revised edition, VEB Deutscher Verlag für Grundstoffindustrie, Leipzig 1985, ISBN 3-342-00280-8 , p. 354.
  2. ^ DE Pearson, Calvin A. Buehler: Friedel-Crafts Acylations with Little or No Catalyst . In: Synthesis . No. 10 , 1972, p. 533-542 , doi : 10.1055 / s-1972-21912 .
  3. ^ Volker Vossius: Contributions to the intra-molecular acylation according to Friedel-Crafts . Munich 1955.
  4. ↑ Joachim Buddrus, Bernd Schmidt: Fundamentals of Organic Chemistry , 5th edition, de Gruyter Verlag, Berlin, 2015, p. 391, ISBN 978-3-11-030559-3 .
  5. ↑ T. Laue and A. Plagens: Name and catchword reactions of organic chemistry , 5th edition, Teubner Studienbücher Chemie, 2006, ISBN 3-519-33526-3 , p. 129.
  6. ^ Z. Wang: Comprehensive Organic Name Reactions and Reagents (3-Volume Set). Volume 1, Wiley, 2009, ISBN 978-0-471-70450-8 , p. 1126.
  7. ^ OC portal .
  8. ^ Mona Hosseini Sarvari, Hashem Sharghi: Reactions on a Solid Surface. A Simple, Economical and Efficient Friedel - Crafts Acylation Reaction over Zinc Oxide (ZnO) as a New Catalyst . In: The Journal of Organic Chemistry . tape 69 , no. 20 , 2004, pp. 6953-6956 , doi : 10.1021 / jo0494477 .
  9. ↑ Mitsuo Kodomari, Yoshitada Suzuki, Kouji Yoshida: Graphite as to effective Catalyst for Friedel-Craftsacylation . In: Chemical Communications . No. 16 , 1997, pp. 1567-1568 , doi : 10.1039 / A703947F .
  10. ^ John O. Morley: Aromatic acylations catalysed by metal oxides . In: Journal of the Chemical Society, Perkin Transactions 2 . No. 5 , 1977, pp. 601-605 , doi : 10.1039 / P29770000601 .
  11. ↑ Vekariya RH, Aubé J: Hexafluoro-2-propanol-Promoted Intermolecular Friedel-Crafts Acylation Reaction . In: Organic Letters . No. 15 , 2016, p. 3534-3537 , doi : 10.1021 / acs.orglett.6b01460 .