Birch reduction

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The Birch reduction [ ˈbəːtʃ- ] is a name reaction in organic chemistry . They convert aromatic systems into non- aromatic systems with the help of alkali metals (so-called dearomatization ). The reaction was developed by Arthur Birch in 1944 , and Charles B. Wooster and Kenneth L. Godfrey began thinking about the reaction as early as 1937.

reaction

Alkali metals such as sodium or lithium , rarely potassium, are dissolved in liquid ammonia for the reaction . This creates solvated electrons that serve as the actual reducing agent. This can be recognized by the deep blue color of the solution. There is also an alkanol , e.g. B. ethanol , required as a proton donor. The reaction proceeds regioselectively , in the form that protonation takes place in the 1,4-position, i.e. two opposing carbon atoms are reduced and two separate double bonds are formed. This regioselectivity is explained by the principle of minimal structural change . If amines are used as solvents instead of ammonia, no dienes are formed, but cycloalkenes ( Benkeser reaction ).

Overview of the Birch reduction

Reaction mechanism

In the first step, a solvated electron is transferred to an antibonding molecular orbital (the LUMO ) of the aromatic ring. A carbanion is formed on one carbon atom while another becomes radical . The carbanion then takes up a proton of an ethanol molecule. Ethanol is only reduced very slowly by solvated electrons, so it can be added before the actual reaction.

Birch reduction part 1

Another carbanion is formed by further uptake of an electron from the solution. This reacts with the proton of a second ethanol molecule and forms the 1,4-dihydrogenated product.

Birch reduction part 2

It should be noted that the remaining two double bonds always remain exactly opposite one another. So no conjugate system is formed.

Reaction on benzene derivatives

Substituents on the aromatic ring influence the regioselectivity of the first protonation on the radical anionic ring. It depends on whether it is an electron acceptor substituent (substituent with a negative I effect ) or an electron donor substituent (substituent with a positive M effect and / or positive I effect). On the basis of qualitative considerations in the case of donor substituents (such as hydroxy or ether groups ), A. Birch himself assumed an initial protonation in the meta position to the substituent. Nowadays, however, this view has been refuted both by theoretical work in the field of quantum mechanics and by experiments, and an initial protonation in the ortho position has been proven.

If, on the other hand, there is an acceptor substituent on the aromatic, the first protonation takes place in the para position or ipso to the substituent. The greater stability of the transition states is responsible for this .

Birch reduction - in para- or ortho-position
Birch reduction - in meta position

Anisoles react to form 1-methoxycyclohexa-1,4-dienes, provided that no other substituents have any influence. The 1-methoxycyclohexa-1,4-diene formed from anisole undergoes proton-catalyzed ether cleavage in an aqueous acidic medium. The immediate product is an unstable enol which, with further proton catalysis ( keto-enol tautomerism ), spontaneously rearranges itself via the cyclohex-3-enone to the more stable (due to conjugation of the double bonds) 2-cyclohexen-1-one . This so-called α, β-unsaturated ketone is used u. a. as a starting material for Michael additions .

Birch reduction of anisole

meaning

The Birch reduction is of particular importance in the synthesis of steroids . C19 steroids were synthesized by Birch reduction of anisole derivatives. (here using the example of methylated estradiol ):

Birch reduction of a steroid derivative

Among other things, the first active, in which was contraceptive pill used estrogen norethisterone or the first totally synthetically prepared anabolic steroid nandrolone by means of a Birch reduction synthesized.

literature

  • Reinhard Brückner: reaction mechanisms. 3rd edition, Spektrum Akademischer Verlag, Munich 2004, ISBN 3-8274-1579-9 .
  • László Kürti , Barbara Czako: Strategic Applications of Named Reactions in Organic Synthesis . Academic Press, 2004, ISBN 0-1242-9785-4 .

Individual evidence

  1. ↑ Arthur J. Birch: Reduction by dissolving metals. Part I. In: Journal of the Chemical Society (Resumed). 1944, pp. 430-436, doi : 10.1039 / JR9440000430 .
  2. ^ Charles Bushnell Wooster, Kenneth L. Godfrey: Mechanism of the Reduction of Unsaturated Compounds with Alkali Metals and Water. In: J. Am. Chem. Soc. 59, No. 3, 1937, pp. 596-597, doi : 10.1021 / ja01282a504 .
  3. ↑ a b c d e Reinhard Brückner: reaction mechanisms. 3rd edition, Spektrum Akademischer Verlag, Munich 2004, ISBN 3-8274-1579-9 , pp. 808-809.
  4. ^ Stefan Kubik: Birch reduction. In: Römpp Chemistry Lexicon. Thieme, as of August 2004.
  5. ↑ Birch, AJ, Nasipuri, D .: Reaction Mechanisms in Reductions by Metal-Ammonia Solutions , Tetrahedron 1959, 148-153.
  6. ^ Howard E. Zimmerman: Orientation in metal ammonia reductions. In: Tetrahedron. 16, No. 1-4, 1961, pp. 169-176, doi : 10.1016 / 0040-4020 (61) 80067-7 .
  7. ^ HE Zimmerman: Base-Catalyzed Rearrangements In: Paul De Mayo (Ed.): Molecular rearrangements. Interscience Publishers, New York 1963, Chapter 6, pp. 345-406.
  8. ^ A b Howard E. Zimmerman, Patricia A. Wang: Regioselectivity of the Birch reduction. In: Journal of the American Chemical Society. 112, No. 3, 1990, pp. 1280-1281, doi : 10.1021 / ja00159a078 .
  9. ^ A b Arthur J. Birch: The Birch reduction in organic synthesis. In: Pure and Applied Chemistry . 68, No. 3, 1996, pp. 553-556 ( full text, pdf ).
  10. ^ Carl Djerassi, L. Miramontes, G. Rosenkranz, Franz Sondheimer: Steroids. LIV. Synthesis of 19-Nov-17α-ethynyltestosterone and 19-Nor-17α-methyltestosterone2. In: Journal of the American Chemical Society. 76, No. 16, 1954, pp. 4092-4094, doi : 10.1021 / ja01645a010 .