4-acyl-2-phenyl-5 -oxazolones

Oxazol-5(2H)-one, 2-benzylidene-4-methyl-tautomerism, 6, 186 Oxazol-5(2ff)-one, 2-methylene-isomerization, 6, 226 Oxazol-5(2H)-one, 2-trifluoromethyl-acylation, 6, 201 Oxazol-5(4ff)-one, 4-allyl-thermal rearrangements, 6, 199 Oxazol-5(4H)-one, 4(arylmethylene)-Friedel-Crafts reactions, 6, 205 geometrical isomerism, 6, 185 Oxazol-5(4ff)-one, 4-benzylidene-2-phenyl-configuration, 6, 185 photorearrangement, 6, 201 Oxazol-5(4ff)-one, 4-benzyl-2-methyl-Friedel-Crafts reactions, 6, 205 Oxazol-5(4ff)-one, 4-methylene-in amino acid synthesis, 6, 203 Oxazol-5(4ff) -one. 2-trifluoromethyl-hydrolysis, 6, 206 Oxazolones... 

Base-catalyzed cyclization of A -benzoyl-a-chloroacetamide is a classical method used to prepare 2-phenyl-4(5//)-oxazolone. Extension of this methodology to the A -aroylcinnamides 35 afforded a series of 5-arylidene analogues 37 albeit in unstated yield (Scheme 6.12). " Thus, acylation of the sodium salt of a benzamide with a cinnamoyl chloride gave the imides 35 that were converted to 36 via a bromination-dehydrobromination sequence. Cyclization to 37 was affected with sodium hydride in 1,2-dimethoxyethane (DME). The authors noted that catalytic reduction of 37 afforded the 5-(arylidene)oxazolidine from which 37 could be regenerated in the presence of air. 

Cyclization of A-acyl-oc-amino acids under acidic reaction conditions is sometimes problematic due to the difficulty in separation of the desired oxazolone from by-products while avoiding decomposition of the reactive oxazolone. This finding is particularly true in the case of 2-phenyl-5(47i)-oxazolone, an interesting compound that is a very useful intermediate to prepare a variety of novel products. The use of carbodiimides as dehydrating agents has been described as a means to improve the results. In particular, treatment of an A-acyl-a-amino acid with A-cyclohexyl-A -2-(A-methylmorpholinio)ethylcarbodiimide p-toluensulfo-nate (Scheme 7.25) is especially useful as a general synthesis of the desired saturated 5(47i)-oxazolones 101 in excellent yields.This same carbodiimide was used to study the kinetics of the formation of saturated 5(47i)-oxazolones from N-protected dipeptides... 

Halogenation Reactions. Chlorination of 4-acyl-2-phenyl-5(4f/)-oxazolones 213 with sulfuryl chloride leads to the corresponding 4-chloro derivatives 214 (Scheme 7.66). These compounds are useful intermediates in organic synthesis. In particular, hydrolytic cleavage of 214 affords a-chloro-a-acylamino ketones... 

Reaction of the 2-phenyl-4-(phosphoranylidene)-5(47/)-oxazolone 219 with alkyl halides gives 4-alkyl-2-phenyl-5(47/)-oxazolones 220 in good yields. Reaction of 219 with acyl iodides or bromides gives C-4- or O-acyl products 221 or 222. Reaction of 219 with acyl chlorides gives 4-(l-chloroalkylidene)-2-phenyl-5(47/)-oxazolones 224 that are Wittig-like products. The use of benzoyl fluoride gives rise to 4-(l-benzoyloxybenzylidene)-2-phenyl-5(47/)-oxazolone 223. These reactions are summarized in Scheme 7.68. 

Reaction of 4-(ethoxymethylene)-2-phenyl-5(47f)-oxazolone 542 with a hydra-zide gives l-acyl-3-hydroxy-17/-pyrazoles 544 via an addition-elimination sequence to generate 543 followed by cyclization as shown in Scheme 7.171. ... 

OxazoIones are alkylated at position 4 by alkyl halides, allyl halides and electrophilic alkynes, such as methyl propiolate (equation 36). In contrast, 2-phenyloxazolones react with methyl vinyl ketone at both C(4) and C(2) to yield a mixture of Michael adducts (equation 37). If the phenyl substituent is replaced by the bulky 2,4,6-trimethylphenyl group the addition is directed exclusively to C(4) (81CB2580). Alkylation of 5(4//)-oxazolones is a key step in the synthesis of ketones from a-amino acids (Scheme 16). The outcome of this sequence is the union of the electrophilic fragment R3 with the group R2CO the amino acid thus functions as the equivalent of an acyl anion (78AG(E)450). 

H)-Oxazolones were unknown until 1949 when the 2-phenyl derivative was prepared by the action of diazomethane on benzoyl isocyanate (equation 145) (49JA4059). Treatment of the phospholene (293) with acyl isocyanates (294 R = Ph, MeO or Ph2N) affords 5-acetyl-5-methyl-4(5.flr)-oxazolones (equation 146). 

Hydrazino-5,6-diphenyl-l,2,4-triazine (289) reacts with 4-benzylidene-2-phenyl-5(4//)-oxazo-lones (290) and 4-benzylidene-3-methyl-5(4//)-isoxazolones (291) in toluene to products (292), (293) substituted in the hydrazino group, the first by acylation by the oxazolone, the second by arylraethylidene group transfer (Scheme 53) <88JHC1813>. 

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-... 

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