Oxazolone structure

Fig. 11 IRMPD spectrum of water loss product from GlyGlyGlyGly compared to computed IR spectra for (a) oxazolone structures, and (b) stractures II and III (Scheme 2). (a) Adapted with permission from Bytheii et ai. [30], Copyright (2010) American Chemical Society, (b) Adapted with permission from Verkerk et al. 31. Copyright (2011) American Chemical Society...

This evidence clearly shows that, at least in the simple case of GlyGlyGlyGly, water-loss products are not predominantly composed of an oxazolone structure caused by the loss of water from the C-terminus, but instead are composed of a structure formed by loss of water from across peptide bonds of the peptide s backbone, in this case probably an imidazolidinone. While this specific fragmentation pathway should not obscure MS/MS sequencing experiments, it is another potential source of confusion for further (e.g., MS ) stages of tandem mass spectrometry. Furthermore, this example underscores the fact that in most instances there are multiple potential fragmentation pathways in competition. 

As with protonated peptides, b-type ions have proved to be, perhaps, the most compelling in terms of potential stmctures. Peptide motifs with and without nucleophilic side chains have been investigated with quite interesting results which are not completely unlike their protonated counterparts. The first two systems studied, AlaAlaAla and AlaTyrAla, both gave rise to b2 ions taking the deprotonated oxazolone structure [38]. It is notable that tyrosine was seemingly uncompetitive as a deprotonation site, in clear contrast to c-type ions. 

In October 1943 I suggested to Chain that penicillin had a p-lactam structure, because 1 could find no basic group in it by potentiometric titrations and because in some of its properties it seemed to resemble an N-acylthiazolidine more closely than a thiazolidine itself. Chain was immediately convinced and the structure was also accepted by Wilson Baker. However, Sir Robert Robinson had already proposed a thiazolidine oxazolone structure (which we thought would be less stable than penicillin) and would hear of no other. He was not alone in his view. One eminent organic chemist in Oxford threatened to give up chemistry if the p-lactam structure was correct. 

Reports from the United States for November and December 1943, which reached London only in February 1944, indicated that the American work on the chemistry of penicillin G had closely parallelled that in Britain on penicillin F and that the Merck group favored the thiazolidine oxazolone structure. But in 1944 the p-lactam structure received strong support from R. B. Woodward at Harvard, who later gave a... 

Five different structures may be written for the oxazolones. Their skeletal formulas, the Chemical Abstracts nomenclature (listed first), and the names with more common usage follow. 

In contrast to the saturated azlactones, the Friedel-Crafts reaction of 2-substituted-4-arylidene-5-oxazolones is quite complex and may follow several different courses, often concurrently, depending on both reaction conditions and structural variations in the arylidene ring. This behavior is readily interpreted in terms of the a,)S-unsaturated carbonyl moiety and the cross-conjugated system containing nitrogen, both of which provide potential reaction sites in addition to the lactone carbonyl group. The reaction has been investigated " ... 

The isolation in poor yield of 2,5,5-triphenyl-4(5f )-oxazolone (82) by reaction of benzilic acid with benzonitrile in concentrated sulfuric acid was claimed by Japp and Findlay. Cornforth, however, suggested that the reactions of this product, m.p. 136°, could be accounted for more satisfactorily by the isomeric 5(4i ) structure 83. 

Aminolysis of activated forms by methylamine provides a convenient derivative for characterizing activated forms. Boc-valine methylamide (Figure 7.37) was the derivative made to confirm the structure of the 2-tert-butoxy-4-isopropyl-5(4//)-oxazolone that had been prepared for the first time (see Section 1.18). However, for activated forms that might undergo enantiomerization or epimerization during aminolysis, hydrazinolysis is the reagent of choice for their derivatization and for establishing the isomeric nature of a substance. Reaction with hydrazine produces... 

The 2(3/T)-oxazolone homopolymer 217 and the 2(37f)-oxazolone copolymer 219 with a carbon-carbon bond backbone structure are readily obtained by heating a 3-acyl-2(3/7)-oxazolone alone or with styrene, respectively, at 70 °C in the presence of BPO with the exclusion of air." " ° The A -acetyl polymers serve as regioselective and chemoselective acylating reagents for amines and alcohols (Fig. 5.53). ° ... 

The 3-acyl-2(3F/)-oxazolones function as good dienophiles in cycloaddition reactions with cyclic 2,4-dienes such as cyclopentadienes and anthracenes. Thus, the thermal reaction of 3-acetyl-2(37/)-oxazolone with cyclopentadiene and the hexachloro and hexamethyl derivatives gives endo-cycloadducts exclusively. In particular, the chiral cycloadducts 221 and 223 derived from the diastereoselective Diels-Alder reactions of 3-(2-exo-alkoxy-l-apocamphanecarbonyl)-2(3/7)-oxazo-lones with hexamethylcyclopentadiene and 9,10-dimethylanthracene, respectively, are highly useful as chiral 2-oxazolidinone auxiliaries. The conformationally rigid roofed structures play a crucial role in affording excellent chiral induction (Fig. 5.54). 

The cyclization of a-halo carboxylic acid ureides can be complicated with products from different modes of cyclization. For example, bromination of 70 at low pH affords the 2-amino-4(5//)-oxazolone 71 in excellent yield, whereas bromination at pH 5-6 generates a mixture of hydantoins 72 and 73 in poor yield (Scheme 6.19)." Japanese workers" reported that cyclization of a-bromoisovaleryl-urea with 28% aqueous ammonia yields 2-amino-5-isopropyl-4(5H)-oxazolone 74, not 75 or 76. The structure of 74 was established spectroscopically and confirmed by hydrolysis to 77 (Scheme 6.20). 

---