5-Acetyl-4-methyloxazole

A solution of 5-acetyl-4-methyloxazole (12.5 g, 0.1 mol) in methanol (125 ml) was added dropwise to a stirred solution of potassium hydroxide (17.5 g, 0.31 mol) in methanol (250 ml) over 10 min at 0-5°C. After 5 min, DIB (36 g, 0.11 mol) was added in five portions over 10 min stirring continued for 4 h at 0-5°C and the reaction mixture was left overnight at room temperature. Then, potassium carbonate was added to saturation and the mixture extracted with dichloromethane (5 x 75 ml). The extract was dried and concentrated addition of benzene (HAZARD) and cooling afforded 5-(2-hydroxy-l,l-dimethoxyethyl)-4-methyloxazole (13 g, 69%), m.p. 63-64°C (from hexane-ether). 

Reaction of a 5-alkoxy-4-methyloxazole with nitroethylene in benzene at -4°, followed by acid hydrolysis, leads to the 3-nitropyrrole 3 (57%).2 1-Nitropropene similarly gave 2-acetyl-4-methyl-3-nitropyrrole (4).3 The initial Diels-Alder adduct under acidic conditions is transformed as in Scheme 2. 

Quinazolin-4(3//)-ones are not readily degraded by reagents in alkaline media because they form stable anions. However, if the tautomeric hydrogen is substituted, then the heterocyclic ring becomes susceptible to cleavage. Two such examples are 3-propadienylquinazolin-4-one (33) and l-acetyl-2-(a-ethoxy-a-phenyl)benzylquinazolin-4-one (34). When the former compound was boiled for 2 hours with sodium in 96% ethanol, nucleophilic attack at C-2 occurred and 2-(2-formamidophenyl)-5-methyloxazole was formed by a subsequent reaction of the olefinic side chain. The second... 

Oxazoles react with amines to form imidazoles. As more examples have been documented, the critical role that the oxazole substitution pattern plays in the reaction outcome has become apparent. For example, 5-acetyl-2-aminooxazole reacts with amines to give imidazoles as the predominant products <84TL2957>. With the addition of a 4-methyl group, as in 5-acyl-4-methyloxazoles or 5-acetyl-2,4-dimethyloxazole, pyrimidines are formed instead <60CB1998,85IJC(B)535>. The reaction of... 

L.23) Ethanone, l-(2-methyl-5-oxazolyl)-, l-(2-methyloxazol-5-yl)ethanone, 5-acetyl-2-methyloxazole [78503-09-0]... 

Mekonnen and Crank also found the same reaction dichotomy in Friedel-Crafts reactions of 622 (X = O) with acid chlorides or acid anhydrides. In general, acylation of 622 (X = O, R = CH3) with acetic anhydride or benzoyl chloride/ pyridine afforded the corresponding 2-(acylamino)-4-methyloxazole 630a and 630b (Scheme 1.174). However, low-temperature acetylation or aroylation of 622 (X = O, R = CH3) in the presence of two equivalents of AICI3 produced a 5-acyl-2-amino-4-methyloxazole 631 in low to modest yield. The authors reported that AICI3 was the most effective Lewis acid (SnCLj and TiCL) and that the reaction required two equivalents of Lewis acid. Selected examples are shown in Table 1.48. 

On occasion, oxazole-alkene Diels-Alder adducts such as 29, and more generally 15, fragment to provide products other than pyridines, depending on the reaction conditions used (Fig. 3.9). The reaction of 5-isopropoxy-4-methyloxazole 28 with nitroethylene therefore gave 31, rather than the expected nitropyridine." " Compound 31 was presumed to form via acid-catalyzed decomposition of the initial Diels-Alder adduct 29 to provide amino-diketone 30, which then cyclized to give 2-acetyl-3-nitropyrrole 31. 

A mixture of 5-ethoxycarbonyloxy-4-methyloxazole (prepn. s. 211) and diethyl fumarate heated 6 hrs. at 90°, cooled, aq. 10%-HCl added, and allowed to stand 0.5 hr. at room temp. 2-acetyl-3,4-di(ethoxycarbonyl)pyrrole. Y 54%. - Pyri-dines are obtained under different conditions (cf. Synth. Meth. 16, 789). M. Murakami et al.. Bull. Chem. Soc. Japan 41, 628, 726 (1968). 

A solution containing 0.1 g A-(4-methyloxazol-2-yl)-lV-(pent-4-enyl)acetamide (0.5 mmol) and 0.06 g DBU (0.4 mmol) in 2 mL toluene in a sealed tube under an argon atmosphere was heated at 180°C for 20 h. Then the solvent was removed under reduced pressure, and the residue was purified by flash siUca gel chromatography to give 0.3 g l-acetyl-7-methyl-l,2,3,4-tetrahydro-l,8-naphthyridine as a pale yellow oil, in a yield of 39%. (Note It requires 0.842 g starting material to afford 39% naphthyridine derivative in a yield of 39%, but it was stated as 0.1 g in the original article.)... 

As an example of the procedure, DL-A-acetyl-2-cyclohexylglycine, by reaction with 3-fluorobenzoyl chloride in the second step, was converted into 5-(4-sulfamoyl-3-fluorophenyl)-4-cyclohexyl-2-methyloxazole (82% yield) (Chapter 6, Section 4.1.2). 

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