The Favorskii rearrangement is principally a rearrangement of cyclopropanones and α-halo ketones that leads to carboxylic acid derivatives. In the case of cyclic α-halo ketones, the Favorskii rearrangement constitutes a ring contraction. This rearrangement takes place in the presence of a base, sometimes hydroxide, to yield a carboxylic acid, but usually either an alkoxide base or an amine to yield an ester or an amide, respectively. α,α'-Dihaloketones eliminate HX under the reaction conditions to give α,β-unsaturated carbonyl compounds.[1][2][3][4][5]
The second step has also been proposed to be stepwise process, with chloride anion leaving first to produce a zwitterionic oxyallyl cation before a disrotatory electrocyclic ring closure takes place to afford the cyclopropanone intermediate.[9]
Usage of alkoxide anions such as sodium methoxide, instead of sodium hydroxide, yields the ring-contracted ester product.
When enolate formation is impossible, the Favorskii rearrangement takes place by an alternate mechanism, in which addition to hydroxide to the ketone takes place, followed by concerted collapse of the tetrahedral intermediate and migration of the neighboring carbon with displacement of the halide. This is sometimes known as the pseudo-Favorskii rearrangement, although previous to labeling studies, it was thought that all Favorskii rearrangements proceeded through this mechanism.
An animation of the reaction mechanism
Wallach degradationedit
In the related Wallach degradation (Otto Wallach, 1918) not one but two halogen atoms flank the ketone resulting in a new contracted ketone after oxidation and decarboxylation[10][11]
Photo-Favorskii reactionedit
The reaction type also exists as a photochemical reaction. The photo-Favorskii reaction has been used in the photochemical unlocking of certain phosphates (for instance those of ATP) protected by so-called p-hydroxyphenacyl groups.[12] The deprotection proceeds through a triplet diradical (3) and a dionespiro intermediate (4) although the latter has thus far eluded detection.[13]
See alsoedit
Syntheses of cubane proceed by Favorskii rearrangements:[14]
^Wohllebe, J.; Garbisch, E. W. (1977). "Ring Contraction via a Favorskii-Type Rearrangement: Cycloundecanone". Organic Syntheses. 56: 107. doi:10.15227/orgsyn.056.0107.; Collective Volume, vol. 6, p. 368
^Shioiri, Takayuki; Kawai, Nobutaka (1978). "New methods and reagents in organic synthesis. 2. A facile conversion of alkyl aryl ketones to α-arylalkanoic acids using diphenyl phosphorazidate. Its application to a new synthesis of ibuprofen and naproxen, nonsteroidal antiinflammatory agents". J. Org. Chem.43 (14): 2936–2938. doi:10.1021/jo00408a049.
^Faworsky, A. Y. (1913). "Über die Einwirkung von Phosphorhalogenverbindungen auf Ketone, Bromketone und Ketonalkohole". J. Prakt. Chem. (in German). 88 (1): 641–698. doi:10.1002/prac.19130880148.
^Akhrem, A A; Ustynyuk, T K; Titov, Yu A (30 September 1970). "The Favorskii Rearrangement". Russian Chemical Reviews. 39 (9): 732–746. Bibcode:1970RuCRv..39..732A. doi:10.1070/rc1970v039n09abeh002019. ISSN 0036-021X.
^Wallach, O. (1918). "Zur Kenntnis der Terpene und der ätherischen Öle. Über das Verhalten zweifach gebromter hexacyclischer Ketone in Abhängigkeit von der Stellung der Bromatome". Justus Liebigs Ann. Chem. (in German). 414 (3): 271–296. doi:10.1002/jlac.19184140303.
^Park, Chan-Ho; Givens, Richard S. (1997). "New Photoactivated Protecting Groups. 6. p-Hydroxyphenacyl: A Phototrigger for Chemical and Biochemical Probes". J. Am. Chem. Soc.119 (10): 2453–2463. doi:10.1021/ja9635589.
^Givens, Richard S.; Heger, Dominik; Hellrung, Bruno; Kamdzhilov, Yavor; Mac, Marek; Conrad, Peter G.; Cope, Elizabeth; Lee, Jong I.; Mata-Segreda, Julio F.; Schowen, Richard L.; Wirz, Jakob (2008). "The Photo-Favorskii Reaction of p-Hydroxyphenacyl Compounds is Initiated by Water-Assisted, Adiabatic Extrusion of a Triplet Biradical". J. Am. Chem. Soc.130 (11): 3307–3309. doi:10.1021/ja7109579. PMC3739295. PMID 18290649.
^ Eaton, Philip E.; Cole, Thomas W. (1964). "Cubane". J. Am. Chem. Soc. 86 (15): 3157–3158. doi:10.1021/ja01069a041.
Further readingedit
Chenier, Philip J. (1978). "Favorskii rearrangement in bridged polycyclic compounds". Journal of Chemical Education. 55 (5): 286. Bibcode:1978JChEd..55..286C. doi:10.1021/ed055p286.
February 06, 2024
favorskii, rearrangement, confused, with, favorskii, reaction, principally, rearrangement, cyclopropanones, halo, ketones, that, leads, carboxylic, acid, derivatives, case, cyclic, halo, ketones, constitutes, ring, contraction, this, rearrangement, takes, plac. Not to be confused with Favorskii reaction The Favorskii rearrangement is principally a rearrangement of cyclopropanones and a halo ketones that leads to carboxylic acid derivatives In the case of cyclic a halo ketones the Favorskii rearrangement constitutes a ring contraction This rearrangement takes place in the presence of a base sometimes hydroxide to yield a carboxylic acid but usually either an alkoxide base or an amine to yield an ester or an amide respectively a a Dihaloketones eliminate HX under the reaction conditions to give a b unsaturated carbonyl compounds 1 2 3 4 5 Favorskii rearrangementNamed after Alexei Yevgrafovich FavorskiiReaction type Rearrangement reactionIdentifiersOrganic Chemistry Portal favorsky reactionRSC ontology ID RXNO 0000385 The Favorskii rearrangementContents 1 History 2 Reaction mechanism 3 Wallach degradation 4 Photo Favorskii reaction 5 See also 6 References 7 Further readingHistory editThe reaction is named for the Russian chemist Alexei Yevgrafovich Favorskii 6 7 8 Reaction mechanism editThe reaction mechanism is thought to involve the formation of an enolate on the side of the ketone away from the chlorine atom This enolate cyclizes to a cyclopropanone intermediate which is then attacked by the hydroxide nucleophile nbsp Favorskii rearrangement mechanismThe second step has also been proposed to be stepwise process with chloride anion leaving first to produce a zwitterionic oxyallyl cation before a disrotatory electrocyclic ring closure takes place to afford the cyclopropanone intermediate 9 Usage of alkoxide anions such as sodium methoxide instead of sodium hydroxide yields the ring contracted ester product When enolate formation is impossible the Favorskii rearrangement takes place by an alternate mechanism in which addition to hydroxide to the ketone takes place followed by concerted collapse of the tetrahedral intermediate and migration of the neighboring carbon with displacement of the halide This is sometimes known as the pseudo Favorskii rearrangement although previous to labeling studies it was thought that all Favorskii rearrangements proceeded through this mechanism nbsp An animation of the reaction mechanismWallach degradation editIn the related Wallach degradation Otto Wallach 1918 not one but two halogen atoms flank the ketone resulting in a new contracted ketone after oxidation and decarboxylation 10 11 Photo Favorskii reaction editThe reaction type also exists as a photochemical reaction The photo Favorskii reaction has been used in the photochemical unlocking of certain phosphates for instance those of ATP protected by so called p hydroxyphenacyl groups 12 The deprotection proceeds through a triplet diradical 3 and a dione spiro intermediate 4 although the latter has thus far eluded detection 13 nbsp See also editSyntheses of cubane proceed by Favorskii rearrangements 14 nbsp Steps in one synthesis of cubane Trimethylenemethane cycloaddition which can proceed via a similar mechanismReferences edit Cope Arthur 1960 Organic Reaction Volume XI 1 ed New York Wiley Interscience doi 10 1002 jps 2600500225 ISBN 9780471171270 Wohllebe J Garbisch E W 1977 Ring Contraction via a Favorskii Type Rearrangement Cycloundecanone Organic Syntheses 56 107 doi 10 15227 orgsyn 056 0107 Collective Volume vol 6 p 368 Shioiri Takayuki Kawai Nobutaka 1978 New methods and reagents in organic synthesis 2 A facile conversion of alkyl aryl ketones to a arylalkanoic acids using diphenyl phosphorazidate Its application to a new synthesis of ibuprofen and naproxen nonsteroidal antiinflammatory agents J Org Chem 43 14 2936 2938 doi 10 1021 jo00408a049 Hamada Yasumasa Shioiri Takayuki 1982 Cycloundecanecarboxylic Acid Organic Syntheses 62 191 doi 10 15227 orgsyn 062 0191 Collective Volume vol 7 p 135 Goheen D W Vaughan W R 1963 Cyclopentanecarboxylic acid methyl ester Organic Syntheses 39 37 doi 10 15227 orgsyn 039 0037 Collective Volume vol 4 p 594 Favorskii A E 1894 J Russ Phys Chem Soc 26 590 a href Template Cite journal html title Template Cite journal cite journal a Missing or empty title help Favorskii A E 1905 J Russ Phys Chem Soc 37 643 a href Template Cite journal html title Template Cite journal cite journal a Missing or empty title help Faworsky A Y 1913 Uber die Einwirkung von Phosphorhalogenverbindungen auf Ketone Bromketone und Ketonalkohole J Prakt Chem in German 88 1 641 698 doi 10 1002 prac 19130880148 Akhrem A A Ustynyuk T K Titov Yu A 30 September 1970 The Favorskii Rearrangement Russian Chemical Reviews 39 9 732 746 Bibcode 1970RuCRv 39 732A doi 10 1070 rc1970v039n09abeh002019 ISSN 0036 021X Wallach O 1918 Zur Kenntnis der Terpene und der atherischen Ole Uber das Verhalten zweifach gebromter hexacyclischer Ketone in Abhangigkeit von der Stellung der Bromatome Justus Liebigs Ann Chem in German 414 3 271 296 doi 10 1002 jlac 19184140303 Wallach O 1918 Zur Kenntnis der Terpene und der atherischen Ole Justus Liebigs Ann Chem in German 414 3 296 366 doi 10 1002 jlac 19184140304 Park Chan Ho Givens Richard S 1997 New Photoactivated Protecting Groups 6 p Hydroxyphenacyl A Phototrigger for Chemical and Biochemical Probes J Am Chem Soc 119 10 2453 2463 doi 10 1021 ja9635589 Givens Richard S Heger Dominik Hellrung Bruno Kamdzhilov Yavor Mac Marek Conrad Peter G Cope Elizabeth Lee Jong I Mata Segreda Julio F Schowen Richard L Wirz Jakob 2008 The Photo Favorskii Reaction of p Hydroxyphenacyl Compounds is Initiated by Water Assisted Adiabatic Extrusion of a Triplet Biradical J Am Chem Soc 130 11 3307 3309 doi 10 1021 ja7109579 PMC 3739295 PMID 18290649 Eaton Philip E Cole Thomas W 1964 Cubane J Am Chem Soc 86 15 3157 3158 doi 10 1021 ja01069a041 Further reading editChenier Philip J 1978 Favorskii rearrangement in bridged polycyclic compounds Journal of Chemical Education 55 5 286 Bibcode 1978JChEd 55 286C doi 10 1021 ed055p286 Retrieved from https en wikipedia org w index php title Favorskii rearrangement amp oldid 1193021729 Wallach degradation, wikipedia, wiki, book, books, library,
