Oxazole-4-carboxaldehyde

Sindler-Kulyk and co-workers " investigated direct formylation of 4-methyl-oxazole 3 and 4,5-dimethyloxazole 611 as a means to prepare analogues that could be further elaborated in their synthesis of vitamin Bg (Scheme 1.166). They isolated a 1 1 mixture of 4-methyl-5-oxazolecarboxaldehyde 609 and 4-methyl-2-oxazole-carboxaldehyde 610 in low yield from 3. Similarly, 611 afforded 4,5-dimethyl-... 

Treatment of aromatic carboxaldehyde (diaminomethylene)hydrazones (105) with hot acetic anhydride or benzoyl chloride affords l,4-diacyl-3-acylamino-5-ary 1-4,5-dihydro- 1H-1,2,4-traizoles (106) in 75-95% yields. In contrast, when the 4-pyridine analog of 105 was employed, the unusual hemianimal triazole derivative (107) was obtained. The structures of the novel compounds were determined by spectral methods and in several cases by x-ray structural analysis. Mechanistic considerations are discussed [95M733]. The oxazole-1,2,4-triazole (108) was prepared by cyclization of the corresponding oxazolecarbonyl-thiosemicarbazide with bicarbonate, alkylation at the sulfur and oxidation to the sulfoxide with MCPBA [95JHC1235]. 

When jV-protected indole-3-carboxaldehydes were allowed to react with tosylmethyl isocyanide, 3-(oxazol-5-yl)-indoles were obtained in satisfactory yields and applied to the synthesis of novel indole-based IMPDH inhibitors <02BMCL3305>. In the same context, a modified approach to 2-(JV-aryl)oxazoles employing an iminophosphorane/ isothiocyanate-mediated methodology and its application to the synthesis of the potent IMPDH inhibitor BMS-337197, was reported <020L2091>. 

In more specific work, adducts of the form TiCl4Lo have been prepared and reported. These include complexes where L = TMEDA,16 benzotriazole,17 benzothiazole,18 2-aminobenzimidazole,19 2-methyl-2-oxazoline, thiazole and a variety of oxazole-derivatives.20 Similarly, complexes of the form TiCl4L (L = RC6H4NH2, R=Bu , Cl, N02, Me21,22 isoxazole, 5-methylisoxazole,20 2-aminobenzimidazole, 2(2 -aminophenyl)benzimidazole,19 2-pyridylphenylacetonitrile22) have been reported. Schifif base adducts of TiCl4 derived from A-methylpyrrole-2-carboxaldehyde, 4-methyl-benzaldehyde, salicylaldehyde, and aromatic or aliphatic amines have also been characterized.23-25 A variety of 2 1 substituted silyl-amine-Ti adducts have also been reported 26-28... 

When 2-oxocyclohexanecarboxaldehyde reacts with hydroxylamine, a mixture of the 1,2- and the 2,1-isoxazole is formed these can be difficult to separate, but when the ketal-carboxaldehyde is used, the product is the 1,2-isoxazole. A similar method was effective on 2-acetylcyclohexanone but some of the 2,1-isomer was formed. A high yield of a pert-fused oxazole is obtained by treating the acridinone (30.4) with PPA at 80 C for 4h. The product is a derivative of an antimalarial drug. 

---