Fischer oxazole synthesis

Source: Wikipedia, the free encyclopedia.
Fischer oxazole synthesis
Named after
Hermann Emil Fischer
Reaction type Ring forming reaction

The Fischer oxazole synthesis is a

heterocycle
.

Fischer Oxazole Synthesis
Fischer Oxazole Synthesis

A more specific example of Fischer oxazole synthesis involves reacting mandelic acid nitrile with benzaldehyde to give 2,5-diphenyl-oxazole.[4]


History

Fischer developed the Fischer oxazole synthesis during his time at Berlin University. The Fischer oxazole synthesis was one of the first syntheses developed to produce 2,5-disubstituted oxazoles.[4]

Mechanism

The Fischer oxazole synthesis is a type of

precipitates as the hydrochloride and can be converted to the free base by the addition of water or by boiling with alcohol.[1]

The

aliphatic
compounds have been used. The first step of the mechanism is the addition of gaseous
carbonyl carbon on the aldehyde
. The following step results in an
HCl molecule to form the product 6, which is the 2,5-diaryloxazole.[4]

Applications

Diarylazoles are common

Robinson-Gabriel synthesis, where the oxazole ring is constructed via either synthesis.[5]

The Fischer oxazole synthesis has also been useful in the synthesis of 2-(4-Bromophenyl)5-phenyloxazole starting with benzaldehyde cyanohydrin and 4-bromobenzaldehyde. However, oxazole ring chlorination occurs to give 2,5-bis(4-bromophenyl)-4-chlorooxazole 7 along with 2,5-bis(4-bromophenyl)-4-oxazolidinone 8. The latter compound is in general a by-product.[6]

Example of a Fischer Oxazole Synthesis
Example of a Fischer Oxazole Synthesis

Another useful example is the one pot two-step synthesis of halfordinol, a parent compound for Rutaceae alkaloids. The initial steps follow the Fischer oxazole synthesis, although the acid-catalyzed cyclization occurs in two steps rather than one, which ensures the formation of the di-chloro intermediate, preventing formation of the regioisomer.[4]

Harfordinal
Harfordinal

In recent research,[citation needed] a reconsideration of the Fischer oxazole synthesis has led to the synthesis of 2,5-disubstituted oxazoles from aldehydes and α-hydroxy-amides. However, unlike the Fischer oxazole synthesis, the new method is not limited to diaryloxazoles.[7]

References

  1. ^
    doi:10.1021/cr60118a002
    )
  2. Fischer, E. Ber.
    1896, 29, 205.
  3. ^ Li, J. J. Fischer Oxazole Synthesis. In Name Reactions: A Collection of Detailed Mechanisms and Synthetic Applications, 4th ed.; Springer-Verlag Berlin Heidelberg: New York, 2003, 229-230. (Review). ([1] Archived 2016-03-04 at the Wayback Machine)
  4. ^ a b c d Maklad, N. Name Reactions in Heterocyclic Chemistry II; Li, J.J.; Wiley & Sons; Hoboken, NJ, 2011, 225-232. ([2])
  5. doi:10.1021/jo100148x
    )
  6. ^ Turchi, I. J. Oxazole Chemistry: A Review of Recent Advances. Ind. Eng. Che. Prod. Res. Dev. 1981, 20, 32-76. ([3]) (Review).
  7. doi:10.1039/JR9490001028
    )
Retrieved from "https://en.wikipedia.org/w/index.php?title=Fischer_oxazole_synthesis&oldid=1182650433"