5-methyl-2-phenyloxazole

The halogenated derivatives of oxazoles, thiazoles80 and benzothiazoles81 were also the subject of palladium catalyzed coupling with terminal acetylenes. 5-Bromo-2-methyl-4-phenyloxazole for example coupled efficiently with phenylacetylene using a conventional catalyst system to give an excellent yield of the desired product (6.53.),82... 

A systematic study of substitution reactions of oxazole itself has not been reported. Bromination of 2-methyl-4-phenyloxazole or 4-methyl-2-phenyloxazole with either bromine or NBS gave in each case the 5-bromo derivative, while 2-methyl-5-phenyloxazole was brominated at C(4). Mercuration of oxazoles with mercury(II) acetate in acetic acid likewise occurs at C(4) or C(5), depending on which position is unsubstituted 4,5-di-phenyloxazole yields the 2-acetoxymercurio derivative. These mercury compounds react with bromine or iodine to afford the corresponding halogenooxazoles in an electrophilic replacement reaction (81JHC885). Vilsmeier-Haack formylation of 5-methyl-2-phenyloxazole with the DMF-phosphoryl chloride complex yields the 4-aldehyde. 

The methyl ester of 2-phenyloxazole-4-carboxylate gives the 5-methyl-derivative when methylated with lead tetraacetate. ... 

Addition of the chiral azaenolate obtained from metalation of (4A,55 )-4,5-dihydro-2-methyl-4-methoxymethyl-5-phenyloxazole (6, see Section D.1.1.1.4.3.3) to aldehydes shows lowdiastere-ofacial selectivity. Acidic hydrolysis of the aldol adducts gives 3-hydroxy adds 7 in 31 -87% yield and less than 25% ee18. 

Treatment of N-benzoyl-L-alanine with oxalyl chloride, followed by methanolic triethylamine, yields methyl 4-methyl-2-phenyloxazole-5-carboxylate 32 <95CC2335>. a-Keto imidoyl chlorides, obtained from acyl chlorides and ethyl isocyanoacetate, cyclise to 5-ethoxyoxazoles by the action of triethylamine (e.g.. Scheme 8) <96SC1149>. The azetidinone 33 is converted into the oxazole 34 when heated with sodium azide and titanium chloride in acetonitrile <95JHC1409>. Another unusual reaction is the cyclisation of compound 35 to the oxazole 36 on sequential treatment with trifluoroacetic anhydride and methanol <95JFC(75)221>. 

Conversion of (M)-4-(l-naphthalenyl)quinoline-3-carboxaldehyde (6) (see p423) to the corresponding methyl ester 7 and comparing the optical rotation with the enantiomeric product ent-1 obtained from (45,55)-4,5-dihydro-4-methoxy-2-[(/>)-4-(l-naphthalenyl)-3-quinolinyl]-5-phenyloxazole (8, see p424). The configuration of 8 was known from an X-ray analysis147. 

The second problem results from the fact that the azaenolates exist as aggregates or mixed aggregates in ethereal solvents. Cryoscopic measurements established that the azaenolate generated from 4,5-dihydro-4-methoxymethyl-2-methyl-5-phenyloxazole and butyllithium in tetrahydrofuran is a dimer18. When the metalation was performed with butyllithium or tert-butyl-lithium, an aging effect was observed. Thus, the enantiomeric excess on alkylation drops from 43% to 28% and 11 % when the azaenolates generated at — 78 °C were allowed to warm to... 

The photolysis of acyl azides has also been studied, and in some respects these appear to behave analogously. Pivaloyl azide, for example, adds to cyclohexene to give a 26% yield of an aziridine [Eq. (85)],321 and the assumption is that this addition again occurs via a nitrene. The photodecomposition of acetyl azide (295) in benzo-nitrile and phenylacetylene, on the other hand, affords322 2-methyl-5-phenyl-l,3,4-oxadiazole (296) and 2-methyl-5-phenyloxazole (297),... 

Although the biosynthesis of 2-pyridyl-5-phenyloxazoles has not been studied, the likely veracity of this sequence has been borne out by the biosynthetic study of annuloline (1) (5) and the cooccurrence in the rutaceous genera Aegle and Amyris of oxazoles and open chain (3-phenylethylamides (11-13, 16, 18). In the biosynthesis of annuloline (1), the low incorporation of O-methylated precursors was a notable point (5) lending support to the possible intermediacy of quinone-methene type compounds such as 31 and 32 and the operation of either a cycliza-tion-alkylation (e.g., 32 to 33) process or a dehydrogenation-alkylation (e.g., 31 to 34) process. 

Attempts to carry out substitution reactions on oxazoles in acid media, such as nitration with nitric and sulfuric acids or chlorosulfonation, fail because the highly electron-deficient oxazolium cation is involved. Phenyloxazoles are nitrated at the para positions of the phenyl groups 2,5-diphenyloxazole affords 5-(4-nitrophenyl)-2-phenyloxazole, as expected. Nitrooxazoles are now available by the action of dinitrogen tetroxide on the corresponding iodo compounds (81JHC885). Benzoxazoles are nitrated at the benzene ring thus 2-methyl-benzoxazole gives a mixture of 5- and 6-nitro derivatives. 

Oxazole N-oxides having a 4-methyl substituent are attacked by acetic anhydride to yield 4-acetoxyoxazoles (equation 21). The combined action of benzoyl chloride and potassium cyanide leads to compounds of the Reissert type, e.g. (177). The reaction of 4-methyloxazole Yoxides with phenyl isocyanate gives 5-hydroxy-4-methylene-l-phenyl-4,5-dihy-droimidazoles by cycloaddition, extrusion of carbon dioxide and recyclization (Scheme 12) with 4-phenyloxazole JV-oxides the reaction takes a different course, yielding imi-dazooxazolidinones (Scheme 13). 

Benzoyl peroxide converts the primary enaminone 154 into the benzoyloxy derivative 155, which is transformed into 5-acetyl-4-methyl-2-phenyloxazole (156) in boiling acetic acid (equation 68)89. 

Methoxycarbonyl)-4,6-dinitrophenyl]-2-(4-methoxyphenyl)-4-phenyloxazol-5(4//)-one affords methyl 2-(4-methoxyphenyl)-7-nitro-4-phenylquinazoline-5-carboxylate (33%) on reflux in methanol in the presence of a catalytic amount of p-toluenesulfonic acid. ... 

Z)-l-(5 -Methyl-l, 3, 4 -thiadiazol-2 -yl)-4-arylidene-4,5-dihydro-2-phenylimidazol-5-ones Z-1496 are prepared by the condensation of (Z)-4-arylidene-4,5-dihydro-2-phenyloxazol-5-ones 1494 with 2-amino-5-methyl-l,3,4-thia-diazoles 1495 on basic alumina under microwave irradiation. The -1496 isomers are also formed as minor products (Scheme 386) <2001S1509>. 

Bicyclo[4.1.0]heptane-7,7-diyl)dimorpholine (3.46 g, 13 mmol) was added to a solution of 4-methyl-2-phenyloxazol-5(4i/)-one (4.55 g, 26 mmol) in MeCN (60 mL). The mixture was allowed to stand overnight. After evaporation of the solvent, 2 M NaOH (20 mL) was added. The crude product was obtained by extracting the aqueous layer with EtjO (2 x 30 mL). Evaporation of the solvent and recrystallization from hexane gave 2.69g (58%) colorless crystals mpll3-114°C. 

The cyclic enolate-type anions 35, 39 and 42, prepared from 4-methyl-2-phenyloxazol-5(4/7)-one,< t.62 2-chlorotropone, " and ) -tropolone, respectively, added to the cyclo-propenylium ions at the enolate carbon. Product 43 from the -tropolone reaction further underwent an intramolecular [4 + 2] reaction to give the cage compound 45. ... 

Methyl-4-(l-methyl-2,3-diphenylcycloprop-2-enyl)-2-phenyloxazol-5(4//)-one (36) Typical Procedure ... 

A study of the effect of A-protonation and aluminum chloride complexation on the C NMR spectra of 2-methyl- and 2-phenyloxazole was reported <85CS266>. Chemical shift data show that protonation and complexation cause a deshielding at C-2 and C-5 and an increased shielding at C-4. 

Proton acidity in oxazole follows the order C-2 > C-5 > C-4. The use of 2-lithiooxazoles in synthesis is problematic, however, because they are in tautomeric equilibrium with their open chain form. When 2-lithiooxazole was reacted with DMF at — 75°C and the mixture was warmed to RT, oxazole-2-carbaldehyde (53) was formed quantitatively. Reaction of this product with a second equivalent of lithiooxazole did not give the expected product, but rather an unsymmetrical bis(oxa-zolyl)methanol (54) <9iJOC449> (Scheme 12). Reaction at the 4 position of lithiooxazole was found to be general for aldehydes. Less reactive electrophiles, such as, DMF, benzophenone, and ethyl formate, gave 2-substituted products, and iodobutane, benzyl bromide and ethyl carbonate did not react at all after an extended age at RT. Acylation of 2-lithio-5-phenyloxazole may be accomplished using A-methyl-7V-(2-pyridinyl)-carboxamides <84S1048>. 

Phenyl-5- and -4-stannyl-thiazoles, prepared via lithium-halogen exchange, are equally reactive in Stille couplings. 2-Phenyloxazole 4-pinacolboronates are prepared by palladium-catalysed boronation of the 5-H-triflate or via lithium-bromine exchange on the 5-methyl-4-bromide. ... 

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