Michael addition

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The Michael addition is a name reaction in organic chemistry . The reaction was named after the American chemist Arthur Michael (1853–1942), who first published it in 1887. It is often used to form carbon-carbon single bonds, but is not limited to this. For example, carbon-sulfur, carbon-oxygen or carbon-nitrogen bonds can also be made.

Overview reaction

It is an addition to an α, β-unsaturated carbonyl compound (Michael acceptor), e.g. B. in α, β-unsaturated aldehydes , ketones , esters or carboxamides . On α, β-unsaturated nitriles - z. B. acrylonitrile - a Michael addition can also take place.

The attacking agent (Michael donor) must be nucleophilic and, according to the HSAB concept, relatively soft. Suitable compounds which can be added are carbanions , ie carbonyl compounds deprotonated by adding a base in the α position . In the following example, the newly formed CC bond is marked in red :

Overview Michael additon V2.svg

As nucleophiles , for. B. organic copper compounds , amines , thiols , phenolate ions or cyanide from hydrogen cyanide can be used. In the past, the Michael addition was carried out exclusively in a protic solvent (such as alcohol) and the corresponding alcoholates were used as the base. By moving to aprotic solvents (example: anhydrous THF ) and sterically hindered and non-nucleophilic base (example: LDA ), the range of applications for the Michael addition was significantly expanded.

Reaction mechanism

In the first step, the Michael donor (here: an ester ) is deprotonated by a base (here: hydroxide ion ) and water is produced. In the further course, the resulting anion reacts with the Michael acceptor (here: an α, β-unsaturated ketone ). The Michael adduct is then formed by protonation and tautomerization .

Mechanism Michael addition V1.svg

In the case of protic solvents, the enolate ion obtained as the primary product is protonated and a further reaction is stopped. However, if the Michael addition is carried out in an aprotic medium, the enolation can lead to further reactions. This can be exploited quite well by providing the enolation resulting from the Michael reaction with a further and now intramolecular Michael acceptor. In this way, e.g. B. by reacting a dienolation of cyclohexadiene derivatives with acrylic acid esters, the preparation of a complex bicyclo [2.2.2] octane ring system is easily possible. Structures of this type are important as starting compounds for the synthesis of complex terpenes in the context of natural product synthesis.

Michael addition 2.svg

The Michael addition is an important reaction in group transfer polymerization (GTP).

Enantioselective Michael addition

Numerous enantioselective embodiments of the Michael addition are known, including the following reactions:

  • Addition of ketones or aldehydes to nitroalkenes or enones
  • Addition of malonic esters to nitroalkenes or enones
  • Addition of diethylzinc to nitroalkenes or enones
  • Addition of N - heterocycles or aldehydes to nitroalkenes or enones
  • Addition of α-hydroxy ketones or aldehydes to nitroalkenes or enones
  • Addition of aryl boric acids

Technical application

The addition of methyl mercaptan (methanethiol) to the carbon-carbon double bond of acrolein leads to methyl mercaptopropionaldehyde (MMP), an intermediate product for the economically important production of DL - methionine , its hydroxy analog (amino group of methionine replaced by hydroxy group) and its salts (above especially sodium and calcium salts). Several 100,000 t of this feed additive are produced every year.

Individual evidence

  1. ↑ Takashi Tokoroyama: Discovery of the Michael Reaction , European Journal of Organic Chemistry 2010 , 10 , 2009-2016 doi : 10.1002 / ejoc.200901130 .
  2. ↑ Arthur Michael: About the addition of sodium acetoacetic and sodium malonic acid ethers to the ethers of unsaturated acids , Journal for practical chemistry, Volume 35, 1887, pp. 349-356.
  3. ^ A b Axel Kleemann , Wolfgang Leuchtenberger, Jürgen Martens and Horst Weigel: A new way to 4-aminobutyric acid amide. In: Angewandte Chemie 1980 , 92 , 640 doi : 10.1002 / anie.19800920815 ; Angewandte Chemie - International Edition English 1980 , 19 , 627. doi : 10.1002 / anie.198006271
  4. ^ Zerong Wang: Comprehensive Organic: Name Reactions and Reagents , Wiley Verlag, 2009, pp. 1922-1925, ISBN 978-0-471-70450-8 .
  5. ^ Dietrich Spitzner, Anita Engler: Aprotic double Michael addition: 1,3-Dimethyl-5-oxobicyclo [2.2.2] octane-2-carbolic acid Template: link text check / apostrophe In: Organic Syntheses . 66, 1988, p. 37, doi : 10.15227 / orgsyn.066.0037 ; Coll. Vol. 8, 1993, p. 219 ( PDF ).
  6. ^ Dietrich Spitzner, Kai Oesterreich: In Anionically Induced Domino Reactions - Synthesis of a Norpatchoulenol-Type Terpene European Journal of Organic Chemistry , 2001 , 10 ; 1883-1886 doi : 10.1002 / 1099-0690 (200105) 2001: 10 <1883 :: AID-EJOC1883> 3.0.CO; 2-M
  7. ↑ Muniappan Thirumalaikumar: Enantioselective Michael Addition Reactions , Organic Preparations and Procedures International 2011 , 43 , 67–129 doi : 10.1080 / 00304948.2011.547102 .

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