Oxazole rings

Oxazoles give acylamino ketones (158) by acid-catalyzed ring scission, although they are somewhat more stable than furans. The oxazole ring is also moderately stable to alkali (74AHCU7)99) as expected, reaction with hydroxide ions is facilitated by electron-with-drawing substituents and fused benzene rings. 

Azolecarboxylic acids can be quite strongly acidic. Thus l,2,5-thiadiazole-3,4-dicar-boxylic acid has first and second values of 1.6 and 4.1, respectively <68AHC(9)107). The acidic strengths of the oxazolecarboxylic acids are in the order 2>5>4, in agreement with the electron distribution within the oxazole ring <74AHC( 17)99). Azolecarboxylic acids are amino acids and can exist partly in the zwitterionic, or betaine, form e.g. 394). 

The Cornforth rearrangement involves the thermal interconversion of 4-carbonyl substituted oxazoles, with exchange between the C-C-O side-chain and the C-C-O fragment of the oxazole ring. These reactions generally involve compounds where a heteroatom (-OR, -SR, -Cl) is attached to the 5-position (R2) of the starting oxazole. 

Wasserman demonstrated with 0 labeling studies that the amide carbonyl oxygen is incorporated into the oxazole ring upon cyclization... 

Pulici and coworkers have reported a solid-phase variation of the Robinson-Gabriel for the production of parallel libraries of ox azole-containing molecules." The preparation is based on a solid supported 2-acylamino ketone 16 that can be cleaved by means of a volatile anhydride and cyclized in solution to obtain a substituted oxazole ring (17) that does not contain traces of the linker moiety. 

Concerning the mechanism of this reaction, calculations suggest that, in the presence of aromatic substituents on the oxazole ring, the ICI mechanism might be favored (83JA1753). 

The oxazole ring can be constructed on a quinoline ring such as 589 by alkylation to give 590 which upon treatment with halogen in CHCI3 gave the corresponding oxazoloquinolinium derivative 591 that upon treatment with... 

Formation of the oxazole ring is not always the last step in synthesis of the brightener. Unsymmetrical compounds that contain both a benzoxazole group and an ethene linkage can be prepared by the anil synthesis [51], in which a compound possessing an activated methyl group reacts with a Schiff base. The preparation of brightener 11.31 is an illustration of this method (Scheme 11.12). 

The silyloxypyrrole 309 was prepared in 91% yield from the ,/3-unsaturated lactam 308 with TBDMSOTf and 2,6-lutidine (Equation 54) <1999TL2525>. Alternatively, the pyrrolo[l,2-f]oxazoles derivatives 311 were prepared by reaction between the stable bcnzotriazol-1 -yl(l //-pyrrol-2-yl)methanone 310 and various ketones (Equation 55) <2004JOC9313>. These two examples are the rare representatives of the pyrrolo[l,2-r ]oxazole ring system described in the literature to date. 

Acyclo-C-nucleoside analogs possessing oxazole rings were obtained from the rearrangement of lactoxime o-vinyl ethers or sugar lactoxime o-vinyl ethers [92JCS(P1)2127]. In some cases, epimerization took place at the C-2 position. 

The structural diversity (and complexity) of the products obtained by the MCR between tertiary isocyano amides, aldehydes, and amines could be increased to various heterocyclic scaffolds by combining the initial 2,4,5-tiisubstituted oxazole MCR with in situ intramolecular tandem processes (Fig. 17). Most tandem processes reported are based on the reactivity of the oxazole ring toward C=C or C=C bonds in hetero Diels-Alder reactions followed by ring opening reactions generating the rather complex heterocyclic products with high degrees of variation. 

The reaction of a-diazocarbonyl compounds with nitriles produces 1,3-oxazoles under thermal (362,363) and photochemical (363) conditions. Catalysis by Lewis acids (364,365), or copper salts (366), and rhodium complexes (367) is usually much more effective. This latter transformation can be regarded as a formal [3 + 2] cycloaddition of the ketocarbene dipole across the C=N bond. More than likely, the reaction occurs in a stepwise manner. A nitrilium ylide (319) (Scheme 8.79) that undergoes 1,5-cyclization to form the 1,3-oxazole ring has been proposed as the key intermediate. 

The oxazole-containing cyclic peptides are synthesized predominately by the direct use of suitably protected 2-(l-aminoalkyl)oxazole-4-carboxylic acids since oxidation of the ox-azolidine precursors to the oxazole ring with Mn0215581 or Ni0215861 (or even with H20215641 or... 

Isocyanides are useful reagents for the preparation of oxazoles unsubstituted at C-2. For example, TosMIC was used to generate the oxazole ring in a synthesis of phthoxazolin A 37 <990L1137>. However in the reaction of IV-tosyl aldimines with the isocyanide 38 the oxazoles that were isolated were 2 1 adducts 39 that had been further substituted at C-2 <98T12445>. 

In Pyrazino[2,3-d]-l, 2-oxazolen ist der 1,2-Oxazol-Ring empfindlich gegeniiber Siiuren und wird in der Hitze leicht geoffnet211. So erhalt man beim Sieden in Ameisensaure oder Acetanhydrid/ Essigsaure in gutcr Ausbeute die Pyrazinyl-1,2,4-oxadiazole z. B. ... 

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