Bergman cyclization

The Bergman cyclization (technical language) or Bergman cyclization is a reaction from the field of organic chemistry . It is a thermal rearrangement with short-lived radical intermediates. It was named after its discoverer, the American chemist Robert George Bergman , who first published it in 1972. The reaction is used to synthesize benzene derivatives from conjugated enediynes in the presence of hydrogen donors .

The Bergman cyclization explains, among other things, the mechanism of action of enediyne antibiotics . There the radical intermediate inserts into the DNA .

mechanism

First, an enediyne with the radicals R ¹ to R ^{4 is} reversibly converted to a 1,4-diyl on heating. This can react in the presence of a hydrogen donor [conveniently often (as in the example) 1,4-cyclohexadiene ] to form a polysubstituted aromatic with the radicals R ¹ to R ⁴ and benzene:

The further the triple bonds in Dialkin are spatially apart, the higher the temperature required; in the case of terminal alkynes , the temperature can be above 200 ° C. Alkynes that already have a cyclic preorientation can usually be made to react at much lower temperatures.

Cyclization at body temperature

In order to achieve cyclization at physiological temperatures , the enediyne unit should be part of a ten-membered ring (n = 1 in the example below).

For example, the biological activity of calicheamicins is based on the cleavage of DNA . If the molecule is transported to the reaction site, a chemical reaction leads to a reduction in the distances between the triple bonds, whereupon a Bergman cyclization to the benzoid diradical takes place, which is able to cleave DNA.

Individual evidence

^ Richard R. Jones, Robert G. Bergman: p-Benzyne. Generation as an intermediate in a thermal isomerization reaction and trapping evidence for the 1,4-benzenediyl structure . In: Journal of the American Chemical Society . Volume 94, No. 2, 1972, pp. 660-661.
^ ^A ^b Thomas Laue, Andreas Plagens: Name and catchword reactions of organic chemistry . Vieweg + Teubner, Wiesbaden 2009, ISBN 978-3-8351-0091-6 .
^ László Kürti , Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis . Elsevier Academic Press, Burlington / San Diego / London 2005, ISBN 0-12-369483-3 .

literature

Jie Jack Li : Name reactions: a collection of detailed reaction mechanisms. Springer, Berlin / Heidelberg / New York 2006, ISBN 978-3-540-30030-4 , p. 49 ( limited preview in the Google book search).

[1] Richard R. Jones, Robert G. Bergman: p-Benzyne. Generation as an intermediate in a thermal isomerization reaction and trapping evidence for the 1,4-benzenediyl structure . In: Journal of the American Chemical Society . Volume 94, No. 2, 1972, pp. 660-661.

[Laue-2] A ^b Thomas Laue, Andreas Plagens: Name and catchword reactions of organic chemistry . Vieweg + Teubner, Wiesbaden 2009, ISBN 978-3-8351-0091-6 .

[Kürti-3] László Kürti , Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis . Elsevier Academic Press, Burlington / San Diego / London 2005, ISBN 0-12-369483-3 .