5- -2-phenyloxazole

C3NO 0 — N — — 2,2 -p-Phenylenebis(5-phenyloxazole) 2-(4-pyridyl)oxazole 2,4-dimethyl-5-(p-nitrophenyl)oxazole 2-oxazolidinone ... 

The cycloaddition of benzonitrile oxide to cis- and rrans-l,2-dichloroethylene produced the appropriate cis- and trans-4,5-dichloro-3-phenyl-2-isoxazoline diastereomers. Base elimination produced only one compound, 4-chloro-3-phenyloxazole (Scheme 103) (70CJC3753). 

In 1959, Crawford and Little reported superior yields of 3 in reactions of aromatic aldehydes by using isolated, crystalline 2-phenyloxazol-5-one (2, Ri = Ph) compared to direct reaction with hippuric acid (1, Ri = Ph). An early report by Boekelheide and Schramm on the use of ketones in the Erlenmeyer azlactone synthesis includes treatment... 

Comforth has reviewed literature reports and independently studied the special cases of reaction of 1 with salicylaldehyde and with 2-acetoxybenzaldehyde. Coumarins (10) are afforded in the condensation of 1 with salicylaldehyde or its imine, whereas when 2-acetoxybenzaldehyde is used, acetoxy oxazolone 12 is the major product. The initial aldol condensation product between the oxazolone and 2-acetoxybenzaldehyde is the 4-(a-hydroxybenzyl)oxazolone 11, in which base-catalyzed intramolecular transacetylation is envisioned. The product 9 (R = Ac) can either be acetylated on the phenolic hydroxy group, before or after loss of acetic acid, to yield the oxazolone 12, or it can rearrange, by a second intramolecular process catalyzed by base and acid, to the hydrocoumarin, which loses acetic acid to yield 10. When salicylaldehyde is the starting material, aldol intermediate 9 (R = H) can rearrange directly to a hydrocoumarin. Comforth also accessed pure 4-(2 -hydroxyphenylmethylene)-2-phenyloxazol-5(4//)-one (13) through hydrolysis of 12 with 88% sulfuric acid. 

The van Leusen reaction forms 5-substituted oxazoles through the reaction of p-tolylsulfonylmethyl isocyanide (1, TosMIC) with aldehydes in protic solvents at refluxing temperatures. Thus 5-phenyloxazole (2) is prepared in 91% yield by reacting equimolar quantities of TosMIC and benzaldehyde with potassium carbonate in refluxing methanol for 2 hrs. ... 

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

Van Leusen and Possel described the use of mono-substituted tosylmethyl isocyanides (TosCHRN=C R = alkyl, benzyl, allyl) in the synthesis of 4,5-substituted oxazoles. For example, 4-ethyl-5-phenyloxazole (8) was prepared in 82% yield by refluxing a-tosylpropyl isocyanide (7) and benzaldehyde for 1 hr with 1.5 equivalent of K2CO3 in MeOH. 

Phenyloxazole, irradiated in benzene at 80°C, gave two products 61, derived from a ring contraction, and 4-phenyloxazole (62), obtained in very low yields (Scheme 25) [73JCS(CC)539 77JCS(P1)239]. The authors thought that 4-phenyloxazole was ascribable to a Dewar intermediate. 

Diphenyloxazole gave only the product of the condensation between the aromatic rings without transposition, while 2,4-diphenyloxazole did not react appreciably [77JCS(P1)239]. However, some important information about the mechanism was obtained when 2-phenyloxazole and 2-phenyl-5-methyloxazole were irradiated with a monochromatic light at 294 nm at 24°C. In both cases, the only... 

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. 

To 0.89 g (4.0 mmol) of (45>,55>)-2-ethyl-4,5-dihydro-4-melhoxymelhyl-5-phenyloxazole and 0.52 g (4.0 mmol) of cthyldiisopropylaminc in 10 rnL of Et20 arc added 1.08 g (4.0 mmol) of 9-borabicyclo[3.3.1]nonyl trifluo-romethanesulfonate30 in a dropwise fashion at — 78 C under nitrogen. The mixture is stirred for 2 h at — 78 °C and 4.0 mmol of the aldehyde are added dropwise at — 78 °C. Stirring is continued at this temperature for 3 h then 20 mL of CH,OH, 9 raL of pH 7 phosphate buffer and 9 mL of 30% H202 are added sequentially. After 45 min at 0 C, workup as described for the anti-esters furnishes 4,5-dihydro-2-(2-hydroxy-l-methylalkyl)-4-methoxymethyl-5-phenyloxazoles 18 as oily products. Without further purification, the crude adducts are heated to reflux in 4.5 N sulfuric acid for 12-14 h. Isolation of the 3-hydroxy esters follows the procedure for an -3-hydroxy esters (vide supra). 

More recently, 4-/m-hutyl- and 4-isopropyl-substituted 4,5-dihydrooxazoles were found to be superior to the original 4-methoxymethyl-5-phenyloxazolines9. Thus, addition of butyl-lithium to 2-(1 - or 2-naphthyl)-substituted 4-ter/-butyl-4,5-dihydrooxazole followed by addition of iodomethane gave adducts in 99 1 and 98.5 1.5 diastereoselection, respectively. The 4-isopropyl analog was less diastereoselective, although the diastereoselection was superior to that of the original 4,5-dihydro-4-methoxymethyl-5-phenyloxazole. 

The role of Lewis acids in the formation of oxazoles from diazocarbonyl compounds and nitriles has primarily been studied independently by two groups. Doyle et al. first reported the use of aluminium(III) chloride as a catalyst for the decomposition of diazoketones.<78TL2247> In a more detailed study, a range of Lewis acids was screened for catalytic activity, using diazoacetophenone la and acetonitrile as the test reaction.<80JOC3657> Of the catalysts employed, boron trifluoride etherate was found to be the catalyst of choice, due to the low yield of the 1-halogenated side-product 17 (X = Cl or F) compared to 2-methyI-5-phenyloxazole 18. Unfortunately, it was found that in the case of boron trifluoride etherate, the nitrile had to be used in a ten-fold excess, however the use of antimony(V) fluoride allowed the use of the nitrile in only a three fold excess (Table 1). 

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>. 

Nitro-2-phenyloxazole, obtained by thermal isomerization of the corresponding nitroi-soxazole, is found to undergo Diels-Alder reactions with 2,3-dimethylbuta-l,3-diene (see Eq. 

The reverse process has also been examined. 2-Phenyloxazole is converted in a similar fashion to 3-phenyl-2//-azirine-2-carbaldehyde on irradiation in benzene or cyclohexane.128 Further rearrangement to the corresponding isoxazole can be effected thermally but not photochemically. A competing pathway leading to the formation of 4-phenyloxazole has also been observed and is thought to involve a bicyclic intermediate arising by 2,5-bonding. 

A simple two-step synthesis of 5H-alkyl-2-phenyloxazol-4-ones has been reported by Trost and coworkers (Scheme 6.209) [377]. a-Bromo acid halides were condensed with benzamide in the presence of pyridine base at 60 °C to form the corresponding imides. Microwave irradiation of the imide intermediates in N,N-dimethylacetamide (DMA) containing sodium fluoride at 180 °C for 10 min provided the desired 5H-alkyl-2-phenyloxazol-4-ones (oxalactims) in yields of 44—82%. This class of heterocycles served as excellent precursors for the asymmetric synthesis of a-hydroxycar-boxylic acid derivatives [377]. 

Interestingly, the alkyne-oxazole Diels-Alder cycloaddition strategy provides a unique entry to some furyl stannanes [52]. Thus, thermolysis of bis(tributylstannyl)acetylene (50) and 4-phenyloxazole (51) led to a separable mixture of 3,4-bis(tributylstannyl)furan (52, 19% yield) and 3-tributylstannylfuran (53, 23% yield). 

Condensation of 2-bromoethylamine hydrobromide with benzoyl chloride in benzene in the presence of 5 equivalents of EtsN gave 2-phenyl-4,5-dihydrooxazole (1) in 67% yield [1]. Treatment of 1 with 3 equivalents of NBS in boiling CCL in the presence of AIBN led to 5-bromo-2-phenyloxazole (2). Presumably, sequential bromination and dehydrobromination of 1 led to 2-phenyloxazole, which underwent further bromination to afford 2. 

The nickel hydroxide electrode resembles in its applications and selectivity the chemical oxidant nickel peroxide. The nickel hydroxide electrode is, however, cheaper, easy to use and in scale-up, and produces no second streams/ waste- and by-products [196], Nickelhydroxide electrode has been applied to the oxidation of primary alcohols to acids or aldehydes, of secondary alcohols to ketones, as well as in the selective oxidation of steroid alcohols, cleavage of vicinal diols, in the oxidation of y-ketocarboxylic acids, of primary amines to nitriles, of 2,6-di-tert-butylphenol to 2,2, 6,6 -tetra-rert-butyldiphenoquinone, of 2-(benzylideneamino)-phenols to 2-phenyloxazols, of 1,1-dialkylhydrazines to tetraalkyltetrazenes. For details the reader is referred to Ref. [195]. 

The tetraphenyl derivative was prepared similarly (DMF/EtOH, 4.5h) (75ZC267). The cyclization can also be done in two steps. A -Alkylation of 2-amino-5-phenyloxazole with desyl bromide yields 2, which on treatment with base (EtOH/KOH, 2.5 h, reflux) gives 3 (75ZC267). 

Structural and theoretical studies on these systems are scarce. A molecular diagram (bond orders, electron densities) of 2-phenyloxazole[3,2-/]xan-thine has been reported (HMO method with standard parameters... 

The cycloaddition reactions of 2-phenyloxazol-4(5H)-one with acetylenic dipolarophiles has been briefly reported. " The formation of 2-phenylfurans may well involve a tautomerism analogous to that exhibited by azlactones (76 77). 

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