Oxazole and Isoxazoles

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. 

The behaviour of /S-oxovinylazides is quite similar to those above. The Z isomer (556), formed from the /S-halo carbonyl compound and sodium azide, is unstable losing N2 and forming the isoxazole (557) in an anchimerically assisted concerted reaction (75AG(E)775, 78H(9)1207). At moderate temperatures (50-80 °C) the E isomer formed acylazirines which at higher temperatures rearranged to oxazoles and isoxazoles. 

DERIVATIVES OF OXAZOLE AND ISOXAZOLE As has been noted previously, the benzene ring of the phenylalkanoic acid antiinflammatory agents can be... 

Berthier, G., R. Bonaccorsi, E. Scrocco, and J. Tomasi. 1972. The Electrostatic Molecular Potential for Imidazole, Pyrazole, Oxazole and Isoxazole. Theor. Chim. Acta 26, 101. 

Oxazole and Isoxazole. These are five-membered ring heterocycles containing oxygen and a nitrogen. Two common forms are oxazole (1,3-oxazole) and isoxazole (1,2-oxazole), both of which undergo aromatic hydroxylation. 

Administration of a cocktail containing eicosapentenoic acid and docosahexenoic acid to volunteers for up to 6 weeks, resulted in a significant depression in IL-1J3 (61%), IL-1 a (39%), and TNF (40%) synthesis. These levels returned to normal after a few weeks [99]. In vitro studies indicate that Pentoxifylline can block the effects of IL-1 and TNF on neutrophils [100]. It is a phosphodiesterase (PDE) inhibitor that causes increased capillary blood flow by decreasing blood viscocity and is used clinically in chronic occlusive arterial disease of the limbs with intermittent claudication. Denbufylline, a closely related xanthine, has been patented as a functional inhibitor of cytokines and exhibits a similar profile to Pentoxifylline [101]. Romazarit (Ro-31-3948) derived from oxazole and isoxazole propionic acids has been shown to block IL- 1-induced activation of human fibroblasts in vitro and in animal models reduces inflammation [102,103,104]. By using a spontaneous autoimmune MRL/lpr mouse model, a significant efficacy was shown [105]. Two-dimensional structures of some of these molecules are shown in Figure 14. 

Several polymerizable oxazole- and isoxazole-functional monomers have been reported in the literature (70MI11100). The polymerizabilities of several alkenyl heterocyclic monomers, including oxazoles (83) and 3-isopropenyl-5-methylisoxazole (84) have been thoroughly studied (75MI11102). These heterocyclic monomers were found to be more... 

Sec. II.B] NITRATION OF PHENYL-SUBSTITUTED HETEROCYCLES 239 5. Oxazoles and Isoxazoles... 

FIGURE 23.2 Examples of oxazoles and isoxazoles in active pharmaceuticals. 

The tetrahydro-derivatives of the oxazole and isoxazole system are unstable. As a consequence, only acyclic products have been reported from the reductions with complex metal hydrides. 2,5-Diphenyl-oxazole (119) gave 2-benzylamino-l-phenylethanol (120),141 and 3,5-diphenyl-2-isoxazoline (121) was converted to 3-amino-l,3-diphenylpropanol (122)142 on reduction with lithium aluminum hydride. 3-Phenylbenzisoxazole was resistant to reduction with lithium aluminum hydride and sodium borohydride,143 but benz-oxazole (123), benzoxazol-2-one (124), and benzoxazol-2-thione (125) have been reported 141 to yield 2-methylaminophenol (126) on reduction with lithium aluminum hydride. 

Imidazoles and their Benzo Derivatives (Hi) Synthesis and Applications 491 4.08.2.2.5 From oxazoles and isoxazoles... 

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