Oxazole-4-carboxamides

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

The preferential formation of ( )-alkene on Wittig reaction of phenyl 3-pyridyl ketones (bearing an oxazole carboxamide group at the / -position of the phenyl ring) with Ph3P=CH(CH2)4C02 K+ has been attributed to interaction between the amide (rather than oxazole) moiety and the carboxyl terminus during oxaphosphetane formation. ... 

Oxazole-containing molecules found several applications in catalysis and materials chemistry. Pyrrolidinyl-oxazole-carboxamide catalysts 140 were reported as new chiral bifunctional organocatalysts effective in the asymmetric Michael addition of ketones to nitroolefins (140BC8008). Compound 141 exhibits different spectral properties (both in absorption and emission) in response to external stimuli, such as pressure and protonation, and it is therefore promising for the realization of piezofluorochromic materials (14CC2569). 

Simple triazoles are thermally stable to ca. 300°C. However, triazole carboxamides, when heated to 150°C in sulfolane, rearrange with the elimination of nitrogen to give 2-substituted oxazoles. The reaction is general and it is useful for the synthesis of oxazoles with diverse 2-substitutents in excellent yields even for bulky substituents (Scheme 1). This reaction does not occur photochemically... 

Davidson s synthesis consists of the cydization of a-acyloxyketones with ammonia or ammonium acetate to give 2,4,5-trisubstituted oxazoles. The Passerini reaction between arylglyoxals, carboxylic acids, and isocyanides afforded N-substituted 2-acyloxy-3-aryl-3-oxopropionamides 83 in high yields. Upon heating with an excess of ammonium acetate in acetic acid, compounds 83 were cydized to N,2,4-trisubstituted oxazole-5-carboxamides 84 in fair yields [59]. A large number of a-acyloxy-jS-ketoamides can be prepared by changing the reaction components, so the method provides straightforward access to a variety of oxazole-5-carboxamides (Scheme 2.30). 

Thermal or photochemical treatment of isoxazoies 851 has been found to result in a ring-contraction reaction to produce acyl 277-azirines 852, which sometimes rearrange to form other heterocycles like oxazoles 853. This ring-contraction reaction can also be promoted by iron(ii) catalysts. Thus, 5-alkoxy- and 5-aminoisoxazoles isomerize to 27/-azirine-2-carboxylic esters and 2/7-azirine-2-carboxamides, respectively, in nearly quantitative yield by reaction with catalytic FeCb (Scheme 212) <1997T10911>. 

Bicyclo[4.1.0]heptane-7,7-diyl)dimorpholine reacted with oxazol-5(47/)-one derivatives in a nucleophilic substitution reaction. - A 1 2 ratio of the reagents was necessary since morpholine as leaving group consumes one mole of oxazol-5(4//)-one to give a carboxamide. 

Proton acidity in oxazole follows the order C-2 > C-5 > C-4. The use of 2-lithiooxazoles in synthesis is problematic, however, because they are in tautomeric equilibrium with their open chain form. When 2-lithiooxazole was reacted with DMF at — 75°C and the mixture was warmed to RT, oxazole-2-carbaldehyde (53) was formed quantitatively. Reaction of this product with a second equivalent of lithiooxazole did not give the expected product, but rather an unsymmetrical bis(oxa-zolyl)methanol (54) <9iJOC449> (Scheme 12). Reaction at the 4 position of lithiooxazole was found to be general for aldehydes. Less reactive electrophiles, such as, DMF, benzophenone, and ethyl formate, gave 2-substituted products, and iodobutane, benzyl bromide and ethyl carbonate did not react at all after an extended age at RT. Acylation of 2-lithio-5-phenyloxazole may be accomplished using A-methyl-7V-(2-pyridinyl)-carboxamides <84S1048>. 

Infrared absorption spectral data for several oxazole derivatives,86 90 including alkyl-98 186 and aryl-263 264 substituted oxazoles, 2-amino- and substituted-amino derivatives109 112 136, 5-amino179 198-201 and 5-alkoxy-oxazoles,66 carboxylic acids,112 147 esters,126 179 184 carboxamides,199 200 4-acetyloxazoles,147 halogenoalkyl oxazoles,91 oxazolines,262 and benzoxazoles262 have been reported. 

Intramolecular cyclization of 4,5-dihydro-3-(2-thienyl)-oxazol-2-ones 39 gave l-hydroxyethylthieno[2,3-d]pyrimidine-2,4(3//)-diones 40 [89JAP(K)242587], The latter compounds were also obtained directly from carboxamides 31 by reaction with 2-chloroethyl chloroformate followed by treatment with ethanolic potassium hydroxide (89H985). 

The initially reported structure of the cyctotoxic ascidian alkaloid 2-bromolep-toclinidinone 105 was amenable to a synthesis approach using an intramolecular oxazole-alkene Diels-Alder reaction, as shown in the retro-synthetic analysis in Figure 3.29. In a model system, the A-benzyl-substituted amide 106 afforded a 50% yield of pyridine 107 after refluxing in benzene for 18 h with 0.75 equivalent of DMAP. The analogous NH-carboxamide faded to provide any of the desired tricyclic pyridine. This was attributed to a conformational preference that allows an internal hydrogen bond between the amide-NH and the oxazole, rather than the conformation that allows efficient overlap of the oxazole and olefin. The yield of 107 could be increased to 87% if the reaction was performed in the presence of the Lewis acid europium(hfc)3. This was not further elaborated since the structure of 2-bromoleptoclinidinone was subsequently revised in 1989. 

According to route II, FGA d (addition of H2O at C-4) gives rise to hydroxyoxazoHne 26, which by disconnection e leads to the iminoester 28 and FGI f to the (a-acyloxy)carbonyl compound 29 and two sets of components, namely 31/33 (via disconnection h) and 34/carboxylate (via disconnection i). Alternatively, 28 can be disconnected according to g leading to components (a-halogeno)carbonyl compound 32/carboxamide. Thus, retrosynthesis proposes systems 27-29 to be suitable educts for approaches to oxazole synthesis [262]. 

Halogeno and (a-hydroxy)ketones undergo cyclocondensation with carboxamides to give oxazoles BlUmlein-Lewy synthesis) ... 

Formamide yields oxazoles unsubstituted in the 2-position urea gives 2-aminooxazoles. As a mechanistic rationale, O-alkylation of the carboxamide should be the primary step (—> 39) followed by cyclization via N C=0 attack (—> 40) and elimination of H2O. 

Alkanenitriles (Linear-alkyl cyanides, 1-Cyanoalkanes) Alkanedinitriles Alkenenitriles Arylnitriles Benzonitrile Aminoethers Oxazole derivatives Oxazole Aminoalcohols Amides (Carboxamides)... 

A preliminary report has described the photolysis of methyl a-isopro-pylidene-4-phenylacetamido-3-isothiazolone-2-acetate (29), a degradation product of penicillin G sulphoxide methyl ester, to the 2-benzylthiazole-4-carboxamide derivative (30 29%), the corresponding oxazole (28%), and the linear dipeptide... 

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