2-Phenyloxazoline

An electrochemical method for the synthesis of a series of 4-(alkylamino)-2-phenyloxazolines 139a-f from A -(2,2-dichlorovinyl)amides 135 has been reported. The starting A -(2,2-dichlorovinyl)amide 135, readily available from chloral and amides, undergoes facile reaction with amines to give 136. Cathodic reduction of 136 generates chlorocarbanionic intermediates 137 and 138 that... 

Yokozawa reported that the 2-substituent strongly affects the reactivity of a 2-substituted-oxazoline 360 with dimethyl 2,2-dicyano-3-ethoxy-l,l-dicarboxylate as shown in Scheme 8.115. Thus, oxazoline itself, 360 (R = H), gave the annulated bicyclic product 361 that resulted from collapse of the zwitterionic intermediate 362, whereas simple 2-alkyloxazolines, 360 (R = Me, Et), gave an alternating (1 1) copolymer. 2-Phenyloxazoline, 360 (R = Ph), was unreactive under the reaction conditions. The zwitterionic intermediate 362 (R = Me) was trapped by acetic acid to give the open-chain adduct 363 that resulted from nucleophilic ring opening at the 5-position of the oxazolinium zwitterion. 

Although lithiation remains the most frequently used metalation reaction, there have been a number of new reports of direct palladation of aryloxazolines. For example, Smoliakova and co-workers prepared the dimeric palladium complex 457 by direct reaction of Pd(OAc)2 with 2-phenyloxazoline in the presence of NaOAc/ HOAc (Scheme 8.150). ° The dimeric complex 457 was converted to the monomeric triphenylphosphine complex 458 for which the X-ray crystal structure was determined. A similar reaction sequence was observed for naphthalenes. Muller... 

For the 2-phenyloxazolines, the reaction is performed, for example, by treating tri-0-acetyl-2-benzamido-2-deoxy-a-D-glucopyranosyl bromide (134) with hydrobromic acid158- 184 to give 135. Alternatively, the unacetylated 2-acylamido-2-deoxy-D-glucose is treated with hydrochloric acid in acetone, and the 5,6-isopropylidene acetal (136) is obtained.165 Compound 136 has proved a valuable intermediate in the synthesis of several amino sugars.186- 172... 

Analogous reactions of pyridylolefins (Eq. 104) [163] and 2-phenyloxazolines [ 164] lead to a mixture of products. 

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... 

Phosgene reacts also readily with substituted oxazo-lines, for example 2-phenyloxazoline, to afford depending on the conditions either N-(2-chloroethyl-N-chlorocarbo-nyl amides or isocyanato ethyl esters as depicted on scheme 130 (Ref. 183, 184). 

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-... 

Another interesting use of these oxazohnes is based on the observation that the 2-phenyloxazolines are metalated very selectively by n-butyllithium at -45° at the ortho-position. This reaction was used for preparation of poly-deuteriobenzoic acids, for example, of (3) from (1). Electrophiles other than D2O can also be used. ... 

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 boratabenzene adduct 53 with [Cr(CO)3(AN)3] produces the f/ (7r)-species 54 along with a free 2-phenyloxazoline (97AGE267, 97JOC8286, 99CSR51). The reaction of sodium 1-methylboratabenzene with [Cr(CO)3(NH3)3] is a simple route to the anionic complexes 55, where Na, PPh4, Hg, H may serve as cations (83JOM(254)143). 

In addition to the above-mentioned reactions, Murai s group developed several other ruthenium-catalyzed carbonylations of arenes with similar reaction conditions (Scheme 6.19). Here, aza-heterocycle [58], 2-phenyloxazolines [59], iV-py-ridylindolines [60], A -arylpyrazoles [61, 62], and 2-phenylpyridines [63], were carbonylated into the corresponding products with Ru3(CO)i2 or Ru/C as the catalyst. Besides these novel carbonylation reactions, ruthenium-catalyzed de-carbonylative cleavage of alkyl phenyl ketones producing phenyl derivatives were also discovered by this group [64]. 

With 1-phenylpyrazoles [150], 2-phenyloxazolines [151], phenyltriazines [152], and A -(l-naphthyl)sulfonamides [153] as substrates, their alkenyladons also proceed in the presence of ruthenium or rhodium compounds, as shown in Eqs. (7.75)-(7.78). 

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). ... 

Investigation of Catalyst Effects in the Synthesis of 2-Phenyloxazoline (19) from Benzonitrile (1 mmol) and 2-Aminoethanol (4 mmol) under Solvent-Eree Conditions at 100 C... 

Good to excellent diastereoselectivities are also obtained with chiral enolates derived from menthol ester 88 [69], Schiffbase of 2-hydroxypinan-3-one 89 [70], bicyclic lactam 90 [71], 2-phenyloxazoline 91 [72], (25,55)-cw-l,3-dioxolan-4-one 92 [73], and imidazolidinone 93 [74, 75] (Fig. 8.4)... 

Phenyloxazolines of the type 18 are susceptible to directed metalation (H-metal exchange [297]) in ortho-position to the oxazoline ring due to intramolecular complexation of the Uthioarene moiety 19 ... 

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). 

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