Mechanism of the Robinson-Gabriel synthesis of oxazoles

He developed the Fischer projection, a symbolic way of drawing asymmetric carbon atoms.
Electron flow mechanism
Applications
Another useful example is the one pot two-step synthesis of halfordinol, a parent compound for Rutaceae alkaloids.

to allow the synthesis of substituated oxazoles from readily available amino acid derivatives.
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The product, which is the 2,5-disubstituted oxazole, precipitates as the hydrochloride and can be converted to the free base by the addition of water or by boiling with alcohol.

The cyanohydrins and aldehydes used for the synthesis are usually aromatic, however there have been instances where aliphatic compounds have been used.


Robinson–Gabriel synthesis topic

Nucleophilic attack of the nitrogen atom and subsequent concerted aromatisation and cleavage provide the oxazole.   Fig.8
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Other methodologies and strategies allowing for the synthesis of compounds 1 that have been investigated include direct alkylation of Rink amide resin; reductive amination of the latter with α-keto aldehydes; reaction of MAMP resin with α-amino alcohols, followed by oxidation; and protection of Rink amide resin with either 2,4-dinitrosulfonyl or allyl group, followed by alkylation and removal of protecting group.


13/06/2014 · Synthesis of Oxazole ..

Substitutedindoles are structural elements of (and for some compounds the syntheticprecursors for) the tryptophan-derived tryptamine alkaloids like theneurotransmitter serotonin, and melatonin.

Trifluoroacetic Anhydride-Mediated Solid-Phase …

Multicomponent reactions (MCRs) are powerful transformations in which three or more starting materials are incorporated in a one-pot manner to produce highly decorated products. Isocyanide-based multicomponent reactions (IMCRs) are of particular interest owing to the large number of starting materials available and a wide range of readily accessible pharmacologically relevant scaffolds. The most well-known IMCR, the Ugi reaction, is carried out through the reaction of an amine, carbonyl compound, carboxylic acid, and isocyanide, which undergoes a condensation step to afford the corresponding functionalized α-acylamino amide. The usefulness of this process as a powerful diversity generating step is demonstrated by tremendous applications in the synthesis of potential drug-like libraries of small molecules., Indeed, an increasing number of elaborate, operationally friendly post-condensation modifications have been developed that employ the Ugi MCR to install structural diversity with strategically positioned internal amine nucleophiles promoting a series of ring-closing events. This methodology has been utilized for the design of pharmacologically relevant molecular scaffolds, some of which have ultimately led to clinical evaluation.

Fischer oxazole synthesis - Wikipedia

Diaryloxazoles are generally prepared through the Fischer oxazole synthesis or Robinson-Gabriel synthesis, where the oxazole ring is constructed via either synthesis.

The Fischer oxazole synthesis has also been useful in the synthesis of 2-(4-Bromophenyl)5-phenyloxazole starting with benzaldehyde cyanohydrin and 4-bromobenzaldehyde.