2-phenyloxazolin-5 -one

Pyrazinecarbohydrazide (204) and 4-ethoxymethylene-2-phenyloxazolin-5-one (206) gave N,N -bis(2-pyrazinecarbonyl)hydrazine (207) and 4-benzami-dopyrazolin-3-one (208) (dioxane, reflux, 30 min 90% the mechanism of hydrogen removal is discussed).1605... 

A new carbon-carbon bond is formed during the reaction of lactim ethers with compounds containing active methylene groups, such as malonic ester and its derivatives, acetylacetone, barbituric acid, rhodanine, nitromethane, and oxindole.8 9 33 100-102 Examples are the condensation of the lactim ether of tetrahydro-/S-carbolinone with acetoacetic ester103 [Eq. (5)] and the condensation of the bislactim ether of 2,2 -dipyrrolidine-5,5 -dione (48) with butyl cyanoacetate20 [Eq. (6)]. Another instance is the reaction of 2 (R = Me) with 2-phenyloxazolin-5-one, to give 3,4-pentamethyleneimidazoles (49) via the intermediate 4-(homopiperid-2-ylene)oxazolin-5-one (50)104 (Scheme 16). 

Scheme 13.14 4-Substituted-2-phenyloxazolin-5-one as substrates for lipases or esterases, with opposite selectivity allowing DKR with in situ racemization.

A method based on the DKR of 4-substituted-2-phenyloxazolin-5-one has been apphed to the large-scale synthesis of N-benzoyl-t-t-leucine-butyl ester 19, an important non-natural amino acid intermediate of several biomimetic peptides. The procedure is based on the alcoholysis of 4-t-butyl-2-phenyloxazoUn-5-one 18 with -butanol catalyzed by the lipase from Mucor miehei (Scheme 13.15) [42]. The unreactive enantiomer is racemized in situ by a base-catalyzed reaction. The... 

The 2-oxazolin-S-ones are excellent acylating agents for a variety of enzymes. Thus, 2-phenyloxazolin-5-one and 4,4-dimethyl-2-phenyl-2-oxazolin-S-one react with a-chymotrypsin, trypsin, and papain to form stable acyl enzymes.15-18 The azlactone from p-nitrobenzoylvaline reacted with a-chymotrypsin and trypsin, and it was observed that the enzymic activity of chymotrypsin decreased with increasing number of p-nitrobenzoylvaline residues.19 The reaction of a-chymotrypsin with 2 has been studied extensively.20-25 In this reaction, the oxazolone dis-... 

Reaction of the 2,5-anhydroallose derivative 54 with 2-phenyloxazolin-5-one (513) in the presence of lead tetraacetate gave the (Z)-4-hexofura-nose-l-ylidene-5-oxazolone 514 (76MI11) (Scheme 132). 

The kinetics of the morpholine-catalysed solvolysis of three 4-X-benzylidene-2-phenyloxazolin-5-ones (36 X=H, Br, MeO) in H2O/DMSO mixtures at different temperatures in the range 313-333 K permitted the determination of AG , A5, and A// for each solvent combination. AG increased gradually as the mole fraction of DMSO increased. As expected, the electron-donating MeO group retarded the rate and the electron-withdrawing Br substituent increased it. The proposed mechanism for the morpholine-catalysed process involves the formation and hydrolytic breakdown of a zwitterionic tetrahedral intermediate, T to generate an A-acylamino acid (37) (Scheme 14). ... 

Phenylazo-2-phenyloxazolin-5-one mixed with glacial acetic acid and HCl, refluxed 5 hrs. l,5-diphenyl-l,2,4-triazole-3-carboxylic acid. Y ca. 80%.— These rearrangements can also be performed in basic media (cf. Synth. Meth. 4, 328). F. e., also pyrazoles, s. A. Mustafa, S. A. Khattab, and W. Asker, Gan. J. Chem. 41, 1813 (1963). 

Figure 36 Enantioselective enzymatic methanolysis of 4-substituted 2-phenyloxazolin-5-one.

The alcoholysis of 2-phenyloxazolin-5-one has been recently reported as an interesting enzymatic reaction for opening of lactones (Scheme 19). This compound, by reaction with iV-ethoxycarbonyl 2-amino-l-butanol in the presence of a lipase in organic solvent, yields an optically active product with moderate enantioselectivity [119]. 

There has been little systematic study of the chemistry of 1,4-oxazepines. Vigorous acid hydrolysis cleaves the amide linkage in (369 R1=Ph, R2 = H) and recyclization gives 2-o-hydroxyphenyl-5-phenyloxazoline and l,2,3,4-tetrahydro-l,8-dihydroxy-3-phenyl-isoquinoline. The l,4-benzoxazepin-5-one (353) can be alkylated at N but on treatment with triethyloxonium fluoroborate it is converted to 5-ethoxy-3-phenyl-l,4-benzoxazepine — one of the very few examples of a fully unsaturated 1,4-oxazepine ring. This product is isomerized to l-ethoxy-4-hydroxy-3-phenylisoquinoline when boiled in methanol. The 4,l-benzoxazepine-2,5-diones (348) are converted to quinazolines by reaction with ammonia. The dihydro-l,4-oxazepin-5-one (343) can be acetylated at nitrogen and bromi-nated at the 6-position. 

Bis(cyclopentadienyl)dichlorozirconium(lI). Chlorotris(isopropoxy)titanium. Di-n-butylboryl trifluoromethanesulfonate. (4S, 5S)-2-Ethyl-4-(methoxymethyl)-5-phenyloxazoline Methyl O-me thy lactate. 2-Methyl-2-trimethylsilyloxypentane-3 one. Morpholine-Camphoric acid. Tin. Tin(II) trifluoromethanesulfonate. 

Sakamoto et al. provided an example of absolute asymmetric synthesis involving hydrogen abstraction by thiocarbonyl sulfur (Scheme 6). [24] Achiral A -diphenylacetyl-iV-isopropylthiobenzamide 33 and Y-diphenylacetyl-A-isopropyl(p-chloro)thio-benzamide 33 crystallize in chiral space group P2 2 2. Photolysis of the chiral crystals in the solid state gave optically active azetidin-2-ones whereas achiral thioketones were obtained as main products. When 33a was irradiated in the solid state at -45°C followed by acetylation (at -78°C), 2-acetylthio-3,3-dimethyl-l-diphenylacetyl-2-phenylaziridine (34a 39% yield, 84% ee), 4-acetylthio-5,5-dimethyl-2-diphenylmetyl-4-phenyloxazoline (35a 10% yield, 50% ee), 3,3-diphenyl-1-isopropy 1-4-... 

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