“Schmidt reaction”的意思、由来-开放百科全书

The Schmidt reaction is an organic reaction in which an azide reacts with a carbonyl group to give an amine or amide, with expulsion of nitrogen.^[1]^[2]^[3] It is named after Karl Friedrich Schmidt (1887–1971), who first reported it in 1924 by successfully converting benzophenone and hydrazoic acid to benzanilide.^[4] Surprisingly, the intramolecular reaction wasn't reported until 1991^[5] but has become important in the synthesis of natural products^[6]

The reaction is effective with carboxylic acids to give amines (above), and with ketones to give amides (below).

Reaction mechanism

The carboxylic acid Schmidt reaction starts with acylium ion 1 obtained from protonation and loss of water. Reaction with hydrazoic acid forms the protonated azido ketone 2, which goes through a rearrangement reaction with the alkyl group R, migrating over the C-N bond with expulsion of nitrogen. The protonated isocyanate is attacked by water forming carbamate 4, which after deprotonation loses carbon dioxide to the amine.

The reaction is related to the Curtius rearrangement except that in this reaction the azide is protonated and hence with different intermediates.

In the reaction mechanism for the ketone Schmidt reaction, the carbonyl group is activated by protonation for nucleophilic addition by the azide, forming azidohydrin 3, which loses water in an elimination reaction to diazoiminium 5. One of the alkyl or aryl groups migrates from carbon to nitrogen with loss of nitrogen to give a nitrilium intermediate 6, as in the Beckmann rearrangement. Attack by water converts 6 to protonated imidic acid 7, which undergoes loss of proton to arrive at the imidic acid tautomer of the final amide. In an alternative mechanism, the migration occurs at 9, directly after protonation of intermediate 3, in a manner similar to the Baeyer-Villiger reaction to give protonated amide 10. Loss of a proton again furnishes the amide. It has been proposed that the dehydration to 3 to give 5 (and, hence, the Beckmann pathway) is favored by nonaqueous acids like conc. H₂SO₄, while aqueous acids like conc. HCl favor migration from 9 (the Baeyer-Villiger pathway). These possibilities have been used to account for the fact that, for certain substrates like α-tetralone, the group that migrates can sometimes change, depending on the conditions used, to deliver either of the two possible amides.^[7]

Reactions involving alkyl azides

The scope of this reaction has been extended to reactions of carbonyls with alkyl azides R-N₃. This extension was first reported by J.H. Boyer in 1955 ^[8] (hence the name Boyer reaction), for example, the reaction of m-nitrobenzaldehyde with β-azido-ethanol:

Variations involving intramolecular Schmidt reactions have been known since 1991.^[5] These are annulation reactions and have some utility in the synthesis of natural products;^[6]^[9] such as lactams^[10] and alkaloids.^[11]

See also

References

1. ^{{cite book |author1=Plagens, Andreas |author2=Laue, Thomas M. |title=Named organic reactions | edition = 2nd |publisher=John Wiley & Sons |location=Chichester |year=2005 |pages= |isbn=0-470-01041-X |oclc= |doi= |accessdate=}}
2. ^{{cite journal|last1=Wolff|first1=Hans|title=The Schmidt Reaction|year=2011|pages=307–336|doi=10.1002/0471264180.or003.08|journal=Organic Reactions}}
3. ^{{cite journal|last1=Lang|first1=S.|last2=Murphy|first2=J. A.|title=Azide rearrangements in electron-deficient systems|journal=Chem. Soc. Rev.|date=2006|volume=35|issue=2|pages=146–156|doi=10.1039/B505080D}}
4. ^{{Cite journal| last1 = Schmidt | first1 = K. F.| title = Über den Imin-Rest| journal = Berichte der deutschen chemischen Gesellschaft (A and B Series)| volume = 57| issue = 4| pages = 704–723| year = 1924 | doi = 10.1002/cber.19240570423 }}
5. ^¹{{cite journal | title = Intramolecular Schmidt reaction of alkyl azides |author1=Jeffrey Aube |author2=Gregory L. Milligan |lastauthoramp=yes | journal = J. Am. Chem. Soc. | year = 1991 | volume = 113 | issue = 23 | pages = 8965–8966 | doi = 10.1021/ja00023a065}}
6. ^¹{{cite journal|last1=Nyfeler|first1=Erich|last2=Renaud|first2=Philippe|title=Intramolecular Schmidt Reaction: Applications in Natural Product Synthesis|journal=CHIMIA International Journal for Chemistry|date=24 May 2006|volume=60|issue=5|pages=276–284|doi=10.2533/000942906777674714}}
7. ^{{Cite journal|last=Crosby|first=Ian T.|last2=Shin|first2=James K.|last3=Capuano|first3=Ben|date=2010|title=The Application of the Schmidt Reaction and Beckmann Rearrangement to the Synthesis of Bicyclic Lactams: Some Mechanistic Considerations|url=http://www.publish.csiro.au/?paper=CH09402|journal=Australian Journal of Chemistry|language=en|volume=63|issue=2|pages=211|doi=10.1071/CH09402|issn=0004-9425}}
8. ^{{cite journal | title = The Acid-catalyzed Reaction of Alkyl Azides upon Carbonyl Compounds |author1=J. H. Boyer |author2=J. Hamer |lastauthoramp=yes | journal = J. Am. Chem. Soc. | volume = 77 | issue = 4 | pages = 951–954 | doi = 10.1021/ja01609a045 | year = 1955}}
9. ^{{cite journal|last1=Milligan|first1=Gregory L.|last2=Mossman|first2=Craig J.|last3=Aube|first3=Jeffrey|title=Intramolecular Schmidt Reactions of Alkyl Azides with Ketones: Scope and Stereochemical Studies|journal=Journal of the American Chemical Society|date=October 1995|volume=117|issue=42|pages=10449–10459|doi=10.1021/ja00147a006}}
10. ^{{cite journal | title = Cation–π Control of Regiochemistry of Intramolecular Schmidt Reactions en Route to Bridged Bicyclic Lactams |author1=Lei Yao |author2=Jeffrey Aubé |lastauthoramp=yes | journal = J. Am. Chem. Soc. | year = 2007 | volume = 129 | issue = 10 | pages = 2766–2767 | format = Communication | doi = 10.1021/ja068919r | pmid = 17302421 | pmc = 2596723}}
11. ^{{cite journal|last1=Wrobleski|first1=Aaron|last2=Sahasrabudhe|first2=Kiran|last3=Aubé|first3=Jeffrey|title=Asymmetric Total Synthesis of Dendrobatid Alkaloids: Preparation of Indolizidine 251F and Its 3-Desmethyl Analogue Using an Intramolecular Schmidt Reaction Strategy|journal=Journal of the American Chemical Society|date=May 2004|volume=126|issue=17|pages=5475–5481|doi=10.1021/ja0320018|pmid=15113219}}