Pyridines oxazoles, review

Sulfur Heterocyclics. Sulfur containing compounds (thiols, thiophenes, thiazoles,. .. etc.) play a major role in the flavor of raw and processed foods. These compounds have characteristic flavor notes and the flavor thresholds are mostly low. Several reviews (ill, 112, 113) demonstrate the important role of sulfur compounds in food flavors. Organoleptic properties of these compounds may be pleasant, strong nut-like odor of U-methyl-5-vinylthiazole which is present in cocoa (llU) objectionable pyridine-like odor of thiazole (115) quinoline-like odor of benzothia-zole (ll6) strong tomato leaf-like odor of isobutylthiazole (117) and bread crust flavor of acetyl-2-thiazoline (ll8). A mixture of oxazoles, thiazoles, thiazolines, imidazoles, trithiolanes and... 

The attacks of heterocyclic A -oxides, e.g. of pyridine, quinoline, isoquinoline, phenanthridine, etc., on activated alkynes (RC CR R = R = COOMe R = Ph, R = COOEt R = Ph, R = CN) pose similar problems . An acyclic intermediate has been postulated but is rarely detected. Some of the possibilities are illustrated in equation (126) . If the open intermediate is formed, then the paths to the ylid and the 2-substituted quinoline in equation (126) seem simple enough, but several possible mechanisms can lead to the 3-substituted products . Other workers regard the reaction of the nitrone (or azomethine oxide) with alkyne as simple cycloadditions - which yield 2,3-dihydro-l,2-oxazoles since these are often unstable, only decomposition products may be found (equation 127). The construction of the indolizine skeleton initiated by a similar process has been reviewed (equation 128). ... 

Subsequent developments, including cyclizations by means of benzene-sulfonyl chloride or silver benzenesulfonate in pyridine, and by phosphoryl or thionyl chloride have already been reviewed by Cornforth.2 4 Of the above cyclodehydrating agents, phosphorus pentoxide is generally preferred to effect cyclizations smoothly 40 for example, phosphorus pentachloride tends to give oxazoles chlorinated in the side chain,60 as shown in Eq. (4). 

The reaction has been very useful for the synthesis of substituted py-ridines, particularly pyridoxine (vitamin Be) and its homologs and analogs. In the last decade a number of papers and patents dealing with the interaction of oxazoles with dienophiles, leading to pyridines, have appeared, they were critically reviewed by Karpeiskii and Florent ev11 in 1969. Therefore, reactions leading to pyridines are described here only briefly, in order to give a clear picture of the scope of the reaction. 

The Diels-Alder reaction of oxazoles with alkenes, alkynes, and heterodieno-philes has become a valuable tool for the construction of highly substituted pyridines, furans, and other heterocycles and has now been exploited for the synthesis of diverse compounds from pharmaceuticals to complex natural products. These reactions have been extensively reviewed. The purpose of this chapter is to provide an introduction to the use of oxazoles in Diels-Alder cycloadditions and an update on these reactions since 1985. 

Because of space restrictions, we have decided to omit a discussion on catalytic cydoadditions, leading to furans, oxazoles, isoxazoles, imidazoles, pyrazoles, pyridines, and other cycloaddition approaches (e.g., [3-1-3], [3-t-2-l-l], and [2-I-2+1+1] to pyridines), but the reader is encouraged to consult the excellent review by Gulevich etal. [45]. 

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