Oxazoles imidazoles

In addition to the reactions described in the preceding section, alkyl groups in the 2-positions of imidazole, oxazole and thiazole rings show reactions which result from the easy loss of a proton from the carbon atom of the alkyl group which is adjacent to the ring (see Section 4.02.3.1.2). 

In general, methyl groups in the 4- and 5-positions of imidazole, oxazole and thiazole do not undergo such deprotonation-mediated reactions, even when the ring is cationic. 

Hydroxy-imidazoles, -oxazoles and -thiazoles (484 Z = NR, O, S) can isomerize to 2-azolinones (485a). These compounds all exist predominantly in the azolinone form and show many reactions similar to those of the pyridones. They are mesomeric with zwitterionic and carbonyl canonical forms e.g. 485a 485b Z = NR, O, S). 

The 4- and 5-hydroxy-imidazoles, -oxazoles and -thiazoles (499, 501) and 4-hydroxy-pyrazoles, -isoxazoles and -isothiazoles (503) cannot tautomerize to an aromatic carbonyl form. However, tautomerism similar to that which occurs in hydroxy-furans, -thiophenes and -pyrroles is possible (499 500 503 504 501 502), as well as a zwitterionic... 

The Neber rearrangement has been used as a valuable synthetic tool to introduce an a-amino group relative to a ketone and it has been used as a key step in the synthesis of a large array of heterocycles, including imidazoles, oxazoles, isoquinolines and pyrazines and has been reviewed long ago °° . ... 

Lewis, J. R. 2001. Amaryllidaceae, muscarine, imidazole, oxazole, thiazole, peptide and miscellaneous alkaloids. Nature Product Reports, 18 95-128. 

Volatiles produced by further interactions pyrroles, pyridines, pyr-azines, imidazoles, oxazoles, thiazoles, thiophenes, dithiolanes, trithi-olanes, dithianes, trithianes, furanthiols... 

Five-membered Rings Imidazoles, Oxazoles, Thiazoles, Dithiolium Salts and Derivatives 568... 

Synthesis of imidazoles, oxazoles and thiazoles from acylamino ketones 569... 

Other syntheses of imidazoles, oxazoles, thiazoles, dithiolyliums and oxathiolyliums by cyclization... 

TT-Electron delocalization in isoxazole seems to be more effective than in oxazole however, isothiazole is less aromatic than thiazole thus it is not a general rule that 1,2-diazoles possess higher aromaticity in comparison with 1,3-diazoles. Oxygen-containing heterocycles are always less aromatic than their sulfur and nitrogen counterparts, e.g. thiazole > imidazole > > oxazole. At the same time, the relative aromaticity of S- and N-containing heterocycles can interchange (pyrazole > isothiazole > isoxazole). 

Photoisomerization of pyrazoles, isoxazoles and isothiazoles into imidazoles, oxazoles and thiazoles, respectively, is described in Section 3.4.1.2.4. 

Aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]-quinazolines Isatoic anhydride could also be reacted with amino-, hydroxyl- or thiolanilines to form 2-(2-aminophenyl)benz-imidazoles, oxazoles or thiazoles, Scheme 5.38. In the case of 2-(2-aminophenyl)benzimidazoles (X=N), the product was formed after 3 min at 150°C in acetic acid. The products could subsequently be further elaborated 6-aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]quinazolines, a four ring system, was formed by treatment of the 2-(2-aminophenyl) benzimidazole (X=N) with different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results). Fifteen compounds were synthesised in 20-75% overall yield. This 3 + 5 min procedure should be compared to the conventional heating protocol developed by Devi and co-workers57, where each reaction step was run overnight to eventually afford the products in only 30-50% yield. 

It is also possible that the order of activating power NH > O > S observed in the rings with only one heteroatom, is also retained in the corresponding azalogs, i.e., imidazole > oxazole > thiazole pyrazole > isoxazole > isothiazole. So far, however, this is a pure speculation since there are no data for a serious homogeneous comparison. 

Synthesis of imidazoles, oxazoles, and thiazoles by C-C bond formation or 1,3-dipolar addition 741... 

Synthesis of imidazoles, oxazoles, and thiazoles by CC bond formation or 1,3-dipolar addition 4-Aminoimidazoles 266 are formed on base treatment of the appropriate precursors 265 (Scheme 130) <1975HCA2192>. Similarly the 4-aminothiazole 268 is obtained from the cyanoamidine 267 (Scheme 131) <1973JPR497>. 

---