1,2-/1,3-Oxazoles Oxazolines

Aqueous mixtures containing a-hydroxyketones (3-hydroxy-2-butanone, l-hydroxy-2-propanone, l-hydroxy-2-butanone) or a-dicarbonyls (2,3-butanedione, 2,3-pentanedione) and ammonium sulfide were reacted at 25 °C for 2 hr. Among the heterocyclic flavor compounds formed were oxazoles, oxazolines, thiazoles, thiazolines and pyrazines. 2-(l-Hydroxyalkyl)-3-oxazolines and 2-( 1 -hydroxyalkyl)-3-thiazolines were major intermediate compounds identified in a-hydroxyketone systems and on the other hand, 5-hydroxy-3-oxazolines and 5-hydroxy-3-thiazolines were proposed as intermediate compounds in o-dicarbonyl systems. 

Takken (2) identified thiazoles and 3-thiazolines from the reaction of 2,3-butanedione and 2,3-pentanedione with ammonia, acetaldehyde and hydrogen sulfide at 20 °C. Study of tetramethylpyrazine (5) also showed that it can be readily formed in 3-hydroxy-2-butanone and ammonia model reaction at 22 C. Recent study of the model reaction of 3-hydroxy-2-butanone and ammonium acetate at low temperature revealed an interesting intermediate compound, 2-(l-hydroxyethyl)-2,3,4-trimethyl-3-oxazoline, along with 2,4,5-trimethyloxazole, 2,4,5-trimethyl-3-oxazoline, and tetramethylpyrazine were isolated and identified 4,5). We hypothesized that with the introducing of H2S, replacement of oxygen by sulfur could happen and sulfur-containing heterocyclic compoimds such as thiazoles and thiazolines could be formed along with oxazoles, oxazolines and pyrazines. 

Of the heterocyclic nitrogen-containing compounds, a-phenylindole is used to stabilize latex polymers and copolymers of vinyl chloride [99]. Melamine has foimd use for the stabilizing of suspension polymers, where a-phenylindole proves inactive [63]. Derivatives of morpholine [274], symmetrical triazine [275], pyrazole [276], as well as derivatives of imidazole, imidazoline, oxazole, oxazoline, thiazole, and thiazoline [277] are recommended in the patent literature for stabilization. 

Lissoclinum Cytotoxic linear amides (bistramides) linear peptides, thiazole-rich cyclic peptides (thiazoline, oxazole, oxazoline and proline) depsipeptides indolic alkaloids pyridoacridines aromatic polysulfanes chlorinated diterpenes (lissodimides and derivatives) macrolides... 

More recent examples have employed a milder reagent system, triphenyl-phosphine and dibromotetrachloroethane to generate a bromo-oxazoline, which is subsequently dehydrohalogenated. Wipf and Lim utilized their method to transform intermediate 11 into the 2,4-disubstituted system of (+)-Hennoxazole k Subsequently, Morwick and coworkers reported a generalized approach to 2,4-disubstituted oxazoles from amino acids using a similar reagent combination, triphenylphosphine and hexachloroethane. ... 

Thus attack of the TosMlC anion 9 on a carbonyl carbon is followed (or accompanied) by ring closure of the carbonyl oxygen to the electrophilic isocyano carbon to form an oxazoline (12). Loss of p-tolylsulfinic acid provides the 5-substituted oxazole 13. ... 

Keywords Diels-Alder reactions of isoxazoles, isoxazolines, isoxazolidines, oxazoles and oxazolines... 

Hayashi et al. [18] have synthesized two diastereoisomers of 2,2 -bis[4-(alkyl)oxazol-2-yI]-l,T-binaphthyl,bis(oxazoline) derivatives possessing both binaphthyl axial chirality and carbon centered chirality (structures 9 and 10, Scheme 5). 

In NRPs and hybrid NRP-PK natural products, the heterocycles oxazole and thiazole are derived from serine and cysteine amino acids respectively. For their creation, a cyclization (or Cy) domain is responsible for nucleophilic attack of the side-chain heteroatom within a dipeptide upon the amide carbonyl joining the amino acids [61]. Once the cyclic moiety is formed, the ring may be further oxidized, to form the oxazoline/thiazoline, or reduced, to form oxazolidine/thiazolidine (Figure 13.20). For substituted oxazoles and thiazoles, such as those... 

Dimethoxyphenyl)-4,4-dimethyl-2-oxazoline Oxazole, 2-(2,3-dimethoxyphenyl)-4,5-dihydro-4,4-dimethyl- (9) (57598-32-0)... 

Cyclization of. V-alkeny lam ides to 2-oxazolines was achieved in very mild conditions with fert-butyl hypoiodite <06OL3335>. The 5-exo-dig gold(I)-catalyzed cyclization of propargylic trichloroacetimidates 129 proceeded with remarkably efficiency under very mild conditions to give 4-methylene-4,5-dihydrooxazoles 130 in good yields. The mildness of the protocol was clearly responsible for the lack of isomerization of the final products to the corresponding, thermodynamically more stable, oxazoles <06OL3537>. 

In addition to palladium catalysts, Co(OAc)2 shows a catalytic activity for the arylation of heterocycles, including thiazole, oxazole, imidazole, benzothiazole, benzoxazole, and benzimidazole.78 As shown in Scheme 6, the catalytic system Co(OAc)2/9/Cs2C03 gives G5 phenylated thiazole, while the bimetallic system Co(OAc)2/CuI/9/Cs2C03 furnishes the G2 phenylated thiazole. The rhodium-catalyzed reaction of heterocycles such as benzimidazoles, benzoxazole, dihydroquinazoline, and oxazoline provides the arylation product with the aid of [RhCl(coe)]2/PCy3 catalyst.79 The intermediacy of an isolable A-heterocyle carbene complex is proposed. 

Oxamidobis-ethyl(3,5-di-tert-butyl-4-hydroxyhydrocinnamate), 3 115 Oxane bonds, silylation and, 22 702-703 Oxazine soluble dyes, 7 373t Oxaziridines, 9 372-373 2-Oxazolines, microwave-assisted synthesis of, 76 576 Oxazoles, 27 151... 

The oxidation state of thiazolines and oxazolines can be adjusted by additional tailoring enzymes. For instance, oxidation domains (Ox) composed of approximately 250 amino acids utilize the cofactor FMN (flavin mononucleotide) to form aromatic oxazoles and thiazoles from oxazolines and thiazolines, respectively. Such domains are likely utilized in the biosynthesis of the disorazoles, " diazonimides, bleomycin, and epothiolone. The typical domain organization for a synthetase containing an oxidation domain is Cy-A-PCP-Ox however, in myxothiazol biosynthesis one oxidation domain is incorporated into an A domain. Alternatively, NRPSs can utilize NAD(P)H reductase domains to convert thiazolines and oxazolines into thiazolidines and oxazolidines, respectively. For instance, PchC is a reductase domain from the pyochelin biosynthetic pathway that acts in trans to reduce a thiazolyinyl-Y-PCP-bound intermediate to the corresponding thiazolidynyl-Y-PCP. ... 

Reaction of Ser-OMe with benzimino ethyl ester resulted in the formation of an oxazoline without racemization (Scheme 27) (85T2379). After forming an amide with 2-amino-l-phenylethanol, Af-phthalimido AAs were oxidized with CrOs and dehydrated by POCI3 to give substituted oxazoles (91JHC1241). 

---