Imidazole oxazole ring

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. 

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

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different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results).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. 

Resistance to oxidative breakdown falls off in the order thiazoles > imidazoles > oxazoles. 2-Substituted thiazoles can be converted into A-oxides, ° however peracids bring about degradation of imidazoles oxazole A-oxides can only be prepared by ring synthesis. Substituted oxazoles are converted into imides, with loss of C-5. ... 

Quaternized oxazoles are readily attacked by hydroxide, ammonia, and amines. Cleavage of the oxazole ring is observed by attack of hydroxide, undoubtedly at position 2, and iV-methyl-a-acylamino ketone (169) is formed.319 Treatment of 2-amino-5-phenyl-3-phenacyloxazolium bromide with ammonia gives 4-phenyl-l-phenacyl-2-imidazolone (170) by ringopening and reclosure. A similar reaction with aliphatic amines (RNH2) leads to 1-substituted 2,6-diphenylimidazo[l, 2-a]imidazoles (171).320... 

Another variant of the Paal method can be identified in the synthesis of the muscle-relaxant azumolene (9.41). This compound contains both the 1,3-oxazole ring and the imidazole ring in the diketo form (hydantoin, 9.42), which is well known in other pharmaceuticals (see section 9.7.). 

Among the five-membered ring heterocyclics with more than one hetero-atom, the derivatives of imidazole, oxazole, thiazole and 1,2,4-triazole are particularly important. 

Imidazole and thiazole ring from oxazole ring... 

The ozonolysis of pyrols, oxazoles, imidazoles, and isooxazoles demonstrates another application of this reaction to the organic synthesis. Pyrols are efficient protective groups of the amino functions in the synthesis of a-aminoalcohols, a-aminoketones, a-aminoaldehydes and some peptides. The oxazole ring is also known as a protective group in the peptide synthesis [92]. 

Many chemical compounds have been described in the Hterature as fluorescent, and since the 1950s intensive research has yielded many fluorescent compounds that provide a suitable whitening effect however, only a small number of these compounds have found practical uses. Collectively these materials are aromatic or heterocycHc compounds many of them contain condensed ring systems. An important feature of these compounds is the presence of an unintermpted chain of conjugated double bonds, the number of which is dependent on substituents as well as the planarity of the fluorescent part of the molecule. Almost all of these compounds ate derivatives of stilbene [588-59-0] or 4,4 -diaminostilbene biphenyl 5-membeted heterocycles such as triazoles, oxazoles, imidazoles, etc or 6-membeted heterocycles, eg, coumarins, naphthaUmide, t-triazine, etc. 

Details of bond lengths and bond angles for all the X-ray structures of heterocyclic compounds through 1970 are listed in Physical Methods in Heterocyclic Chemistry , volume 5. This compilation contains many examples for five-membered rings containing two heteroatoms, particularly pyrazoles, imidazoles, Isoxazoles, oxazoles, isothlazoles, thlazoles, 1,2-dlthloles and 1,3-dlthloles. Further examples of more recent measurements on these heterocyclic compounds can be found in the monograph chapters. 

The carbon atoms of azole rings can be attacked by nucleophilic (Section 4.02.1.6 electrophilic (Section 4.02.1.4) and free radical reagents (Section 4.02.1.8.2). Some system for example the thiazole, imidazole and pyrazole nuclei, show a high degree of aromati character and usually revert to type if the aromatic sextet is involved in a reaction. Othei such as the isoxazole and oxazole nuclei are less aromatic, and hence more prone to additio reactions. 

A multiply bonded nitrogen atom deactivates carbon atoms a or y to it toward electrophilic attack thus initial substitution in 1,2- and 1,3-dihetero compounds should be as shown in structures (110) and (111). Pyrazoles (110 Z = NH), isoxazoles (110 Z = 0), isothiazoles (110 Z = S), imidazoles (111 Z = NH, tautomerism can make the 4- and 5-positions equivalent) and thiazoles (111 Z = S) do indeed undergo electrophilic substitution as expected. Little is known of the electrophilic substitution reactions of oxazoles (111 Z = O) and compounds containing three or more heteroatoms in one ring. Deactivation of the 4-position in 1,3-dihetero compounds (111) is less effective because of considerable double bond fixation (cf. Sections 4.01.3.2.1 and 4.02.3.1.7), and if the 5-position of imidazoles or thiazoles is blocked, substitution can occur in the 4-position (112). 

The distinction between these two classes of reactions is semantic for the five-membered rings Diels-Alder reaction at the F/B positions in (269) (four atom fragment) is equivalent to 1,3-dipolar cycloaddition in (270) across the three-atom fragment, both providing the 47t-electron component of the cycloaddition. Oxazoles and isoxazoles and their polyaza analogues show reduced aromatic character and will undergo many cycloadditions, whereas fully nitrogenous azoles such as pyrazoles and imidazoles do not, except in certain isolated cases. 

As shown in Scheme 2, two heteroatom-carbon bonds are constructed in such a way that one component provides both heteroatoms for the resultant heterocycle. By variation of X and Z entry is readily obtained into thiazoles, oxazoles, imidazoles, etc. and by the use of the appropriate oxidation level in the carbonyl-containing component, further oxidized derivatives of these ring systems result. These processes are analogous to those utilized in the formation of five-membered heterocycles containing one heteroatom, involving cyclocondensation utilizing enols, enamines, etc. 

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