4.5- diaryl-2-substituted oxazoles

The UV and fluorescence characteristics of simple substituted oxazoles have been discussed in the early review, which also made mention of the utility of 2,5-diaryl derivatives as scintillators (3). Among the natural products, the 2,5-diaryl compounds halfordinol (16), halfordine (17), O-isopentenylhalfordinol (19), balsoxin (25), O-methylhalfordinoI (22), compound 24, texamine (26), and texa-line (27) reportedly display a high intensity (log e 3.61-4.63) band in the range 323-354 nm (Table III). In the 2-pyridyl-5-phenyl derivatives this band undergoes a bathochromic shift of 17-23 nm on acidification (Table III), which may be rationalized by the formation of the pyridinium salt (e.g., 204) for O-isopentenylhalfordinol (19). In 204 the 2-pyridinium substituent is obviously... 

In 1977 Davis, Temai et al. introduced an interesting variation to the synthesis. In their efforts to form substituted 2,5-diaryl oxazoles, a simple modification of the Fischer oxazole synthesis rendered a good yielding process. Acyl cyanide replaces cyanohydrins, which reacts with aldehyde to form 2,5-diaryl-4-chloro- (or bromo-) oxazoles. An example for such variation is the synthesis of the chloro-oxazoles 14. Benzoyl cyanide (12) reacts with aldehyde 13a at 0 C in the presence of HCl, and the mixture is stirred overnight to give 14a in a 75% yield. Similarly, benzoyl cyanide reacts with aldehyde 13b to give 14b in a 65% yield. 4-Bromo-oxazoles can also be formed using such variation. An example is the synthesis of 16 by the reaction of p-nitrobenzoyl cyanide (15) with benzaldehyde in the presence of HBr the 4-bromo adduct is formed in a 68% yield. 

Direct Carbonylative Coupling. Unsymmetrical diaryl ketones were synthesized via the direct carbonylative coupling of aryl iodides and heteroarenes in the presence of catalytic [PdCl(cinnamyl)]2, l,3-bis(diphenylphosphino)propane (dppp) as the ligand, and stoichiometric Cul. Thus, heterocycles such as oxazoles, benzoxazoles, thiazoles, benzothiazoles, and imidazoles reacted, with 4-iodoanisole in 56-75% yields (eq 1). Aryl iodides containing a variety of electron-donating or electron-withdrawing substitutents were tolerated in the reaction (eq 2) however, aryl bromides provided only traces of products. The role of the stoichiometric copper salt was to form a heteroaryl-Cu species, which could easily transmetallate to Pd. No reaction was observed in the absence of the Cul additive. 

Low yields were obtained in the absence of pivalic acid however, employing greater than 30% pivalic acid did not further improve yields or reactivity. Substrates that performed well included C3-substituted benzothiophenes, C2-substituted thiophenes, pyrroles, imidazole, triazole, imidazopyridine, thiazole, and oxazoles, which could be efficiently arylated with aryl bromides. Unfortunately, benzofuran produced low yields (29% with 2-bromotoluene), and furans encountered issues with diarylation, which could be minimized by using more sterically hindered aryl bromides. Arylation of indolizines could be achieved, albeit electron-deficient aryl bromides required longer reaction times (16-24 h). Heterocyclic aryl bromides, such as 3-bromopyridine, could also be employed with thiazole. Problematic aryl halides included cyano, nitro, acetyl, pyridyl functionalities, and N-heterocyclic V-oxides. Other coupling partners, such as aryl tri-flates and aryl chlorides, performed poorly under the reaction conditions. Unsuitable heterocycles included unprotected imidazoles, 2-aminothiazole, isoxazole, benzothiazole, and benzoxa-zole, which failed to produce arylated products. 

Figure 5. Sealed Tube DSC Spectra of Acceptor-Substituted Diaryl-Oxazoles (II-a,b).

From Table 1, below, no signs of thermal decomposition were observed below 400 °C for nitrile and sulfonyl substituted di-and triaryl oxazoles. Nitro compounds, in contrast, exhibited marked thermal decomposition exotherms with decomposition onset temperatures of 360-365 °C, conditions only marginally compatible with polyimide curing conditions. Nitro aromatics are also oxidants which may lead to long-term stability problems. As a result of these experiments nitrile and sulfonyl substituted diaryl oxazoles were selected for polymer doping studies. 

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