Oxazole derivatives

The reaction of cyclohexene with the diazopyruvate 25 gives unexpectedly ethyl 3-cyclohexenyl malonate (26), involving Wolff rearrangement. No cyclo-propanation takes place[28]. 1,3-Dipolar cycloaddition takes place by the reaction of acrylonitrile with diazoacetate to afford the oxazole derivative 27[29]. Bis(trimethylstannyl)diazomethane (28) undergoes Pd(0)-catalyzed rearrangement to give the A -stannylcarbodiimide 29 under mild conditions[30]. 

Photolysis, luminiscent properties, and laser activity of oxazole derivatives 97MI27. 

Condensation of the 2-quinolone 633 with ethyl 3-chloroacrylate gave the oxazole derivative 634 (79YZ813). Cyclization of 635 with l,l -carbonyldi-imidazole gave 636 (92JMC1076) (Scheme 109). 

A number of oxazole derivatives were also synthesised, of which (508) was among the most potent (IC50 = 80 nM). In general however, the binding affinities reported for the oxazole compounds were at best modest, and comparable with the related imidazole NH series (data not shown). 

Application of the Ritter reaction conditions on y-hydroxy-a,P-alkynoic esters, 102, produced ethyl 5-oxazoleacetates 103 or y-A-acylamino-P-keto ester 104 by reaction with aryl or alkyl nitriles respectively. The y-A-acylamino-P-keto ester 104 can also be transformed into oxazole derivatives using an additional step involving POCI3 <06TL4385>. 

The silyloxypyrrole 309 was prepared in 91% yield from the ,/3-unsaturated lactam 308 with TBDMSOTf and 2,6-lutidine (Equation 54) <1999TL2525>. Alternatively, the pyrrolo[l,2-f]oxazoles derivatives 311 were prepared by reaction between the stable bcnzotriazol-1 -yl(l //-pyrrol-2-yl)methanone 310 and various ketones (Equation 55) <2004JOC9313>. These two examples are the rare representatives of the pyrrolo[l,2-r ]oxazole ring system described in the literature to date. 

Transition metal-catalyzed reactions of ct-diazocarbonyl compounds proceed via electrophilic Fischer-type carbene complexes. Consequently, when cr-diazoketone 341 was treated, at room temperature, with catalytic amounts of [ RhiOAcbh, it gave the formation of a single NH insertion product, which was assigned to the enol stmcture 342. At room temperature, in both solid state and in solution, 342 tautomerizes to give the expected 1-oxoperhydropyr-rolo[l,2-c]oxazole derivative 343 (Scheme 50) <1997TA2001>. 

Lewis acid SnCLj-assisted reaction between the l,3-thiazole-5-thione 434 and /ra r-2,3-dimethyloxirane led to the m 4,5-dimethyl-l,3-oxathiolane 435 The same Lewis acid enabled a second addition of /ra/ -2,3-dimcthyloxirane onto the C—N bond of the 1,3-thiazole ting of 434, leading to the formation of the tetrahydro-2//-thiazolo[2,3- ]-oxazole adduct 436 (Equation 200) <2000HCA3163>. Condensation of 2,4-dinitroimidazole, 8-bromotheophylline, and 8-bromoadenine with substituted methyloxiranes involved sequential A -alkylation-r/wo-substitution and furnished a series of 2,3-dihydro-imidazo[2,l- ]oxazole derivatives 437, 438, and 439 (Equations 201-203) <2000CCC1126, 2000EJ03489, 2005TL3561, 2004JHC51>. 

Heterocyclic ring systems are also used to connect two anthraquinone groups. Typical examples include Cl Vat Red 10 (6.106), which is an oxazole derivative obtained from 2-amino-3-hydroxyanthraquinone and the appropriate acyl chloride, the similar thiazole derivative Cl Vat Blue 31 (6.107) and the oxadiazole derivative Cl Vat Blue 64 (6.108). 

Cycloaddition reactions involving thermal/photochemical/catalytic decomposition of iodonium ylides are applicable to oxazole derivatives... 

Additional heterocyclic ring systems, such as benzofurans [125], dihydropyrroles and dihydroazepines [41], piperidines and dihydropyrimidines 36 [126], and fused oxazole derivatives [127], have been described (Eq. 7). The formation of epoxides and aziri-dines, formally emanating from ylides, was recently reported by Doyle et al. [77]. Rho-dium(II)-catalyzed isomiinchnone cycioaddition followed by Lewis acid-mediated ring opening has been used as an entry into the protoberberine azapolycyclic ring structure [128]. 

Bossio R, Marcaccini S, Pepino R (1991) Synthesis of isocyanides and related compounds. Synthesis of oxazole derivatives via the Passerini reaction. Liebigs Ann Chem 1107-1108... 

From the same laboratories, a series of heterocyclic ketones were published as HDAC inhibitors [61]. This work is a continuation and further elaboration of the concept of the use of electrophihc ketones as hydroxamic acid replacements. a-Keto oxazole derivatives appeared to act as the most potent HDAC inhibitors in the HDAC1/HDAC2 enzyme assay [60], displaying low micromolar activity (Fig. 9). 

Thermal synthesis of 2-substituted phenanthroxazoles and related compounds by cyclization of O-methyl o-quinone oximes with compounds ArCH2Y (Ar = aryl, hetaryl Y = H, OH, Cl, Br, OAc, SH, COR, NH2) or with amines (PhCHiNMej, PhNHMe, PhNMe2) has been described. Cyclization of a-oxooximes in the system alkyl halide or sulfate/DMF/K2C03 also leads to oxazole derivatives . 

Substituted binaphthyl compounds can be synthesized in high optical yields using nucleophilic aromatic substitution reactions in which the chiral leaving groups are alkoxy moieties derived from naturally occurring alcohols28-29. For example, the condensation of 2-(l-alkoxynaphth-2-yl)-4.5-dihydro-4,4-dimethyl-l,3-oxazole with 1-naphthyllithium or 2-methoxy-l-naphthyl 2-magnesium bromide leads to (ft)- or (.S)-(l,T-binaphthyl-2-yl)-4,5-dihydro-4,4-dimethyl-l,3-oxazole derivatives. 

The hydrolysis of the Schiff base 63 is an acid-catalyzed reaction initiated by the protons liberated during the anodic oxidation. A successful synthesis could be achieved in an undivided cell. The starting compound 63 was oxidized at the anode, and the liberated protons were reduced at the cathode the solution did not become too acidic. This reaction was applied to the oxidation of 3-arylidenamino-4-hydroxycoumarin, which gave the expected 1,3-oxazole derivatives.78 The mechanism of the conversion 63 -> 64 involves... 

D) Oxazole derivatives R Austr. Appl. Brit. 62,296 (I960) 889,186 (1962)... 

In a similar manner (initially at the nitrogen atom, rather than at the hydroxyl group and then according to the scheme of 1,3-dipolar addition), acetoxime reacts with methyl esters of propiolic and acetylenedicarbox-ylic acids in DMF or DMSO to form, however, not pyridines but the 1,2-oxazole derivatives 150 (Scheme 75) (67AG722 69CB2336, 69CB-2346). 

Oxazole Derivatives and Imidazoles by Passerini-3CR or Ugi-4CR and Davidson Cydization... 

Scheme 63 Self-sensitized photo-oxygenation of the oxazole derivative 163.

Schemes.19. Regioselective derivatization of an oxazole-derived dianion [180],...

The photochromic spiroindolinonaphth[2,l-fc][l,4]oxazines conjugated with aza-15(18)-crown-5(6) ether moieties or morpholine in the presence of Pb2+ or Eu3+ give highly coloured betaine merocyanine, the open form of the compound, which can return to the initially closed non-coloured form by irradiation with light (Scheme 125).188 When the merocyanine complexes are kept in the dark, the corresponding oxazole derivatives are formed irreversibly and regioselectively. 

Chiral thietanes with mesogenic groups have been used as novel liquid crystals (95SC2665). The oxazole derivatives (42) readily undergo thermal rearrangement to the thietan-3-imines (43) (95CC67). 

Evaluation of the scavenging activity for H2O2 by NSAIDs, namely indole derivatives (indomethacin, acemetacin, etodolac), pyrrole derivatives (tol-metin, ketorolac), oxazole derivative (oxaprozin), indene derivative (sulin-dac) and its metabolites (sulindac sulfide and sulindac sulfone) was performed by Costa et al. [ 103]. The obtained results against endogenous antioxidants melatonin and GSH demonstrated that all the studied NSAIDs display... 

Desyl chloride (80) also yields oxazole derivatives (78) when it reacts with several nitrile-stannic chloride complexes,60 but other chloroketones studied either do not react (2-chlorocyclohexanone and... 

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