Oxazoles 2-ethoxy

Oxazoles preferred in practice bear 5-ethoxy- or 5-cyanosubstituents. Other alkoxy (39—42), trimethylsilyloxy (43), alkythio (44), amino (45), and... 

Huisgen et al. also studied the thermal decomposition of ethyl diazoacetate in the presence of benzonitrile and phenylacetonitrile to give the corresponding 2-substituted-5-ethoxy oxazoles 3 in variable yields (Scheme 3).<64CB2864> The authors found that the solvent had an effect on the rate of decomposition of ethyl diazoacetate in the polar solvent, niuobenzene, the rate was found to be twice that in the hydrocarbon solvent, decalin. 

Aromatic acid chlorides and 2-(triphenylphosphoranylidenamino)cinna-mates (127) give rise to l,3-oxazol-5-ones (129), as shown in Scheme 51. After an intermolecular aza-Wittig reaction with 127, the ethoxy O attacks... 

Methyl-2-phenyl-oxazol-4-yl)ethoxy]benzo[2]thiophen-7-yl]methyl]-thiazolidine-2,4-dione. 

Thiazoles also undergo Diels-Alder additions, but have been used less. In the examples shown, 5-ethoxy-4-methylthiazole is converted into the pyridinedicarboxylic acid (738), and into pyridoxine (737) (65FRP1400843). The mechanism must be similar to that proposed for the oxazole additions. In both cases the initial adducts are treated with hydrochloric acid sulfur dioxide is said to be given off in the first case, hydrogen sulfide in the second, the latter providing an analogy with the oxazole mechanism. 

Oxazoles may be similarly prepared in good yields. Thus, 5-ethoxy-4-methyloxazole (173) was obtained by treating ethyl 2-formamide propionate (172) with phosphorus pentoxide in chloroform at 55°C (72JCS(P1)909,914). Known collectively as the Robinson-Gabriel synthesis, these cyclodehydrations can be effected by sulfuric acid or anhydrous hydrogen fluoride (cf CHEC 4.18). 

Corn inei ciaHy, the vitamin is available as a dietary supplement in the, compound pyridoxine hydrochloride. The compound can be synthesized by condensing ethoxy acetylacetone with cyanoacetamide (method of Harris and Folkers) or from oxazoles. 

Upon mixing 1.27 g of 4-methyl-5-ethoxy oxazole (0.01 mole), 0.98 g of maleic anhydride (0.01 mole) and 2.5 ml of dry benzene, a yellow color appears and heat is evolved, requiring cooling. After 3-4 min the evolution of heat ceases and the color fades. The mixture is then refluxed for about 18 h, after which the solvent is decanted and the residue treated with a small... 

Oxazolium salts are easily attacked by nucleophiles. The hydrolysis of oxazoles and benzoxazoles by hydrochloric acid has long been known. Triphenyloxazole gives benzoic acid, benzaldehyde and ammonium chloride 2-methylbenzoxazole affords o-acetamido-phenol, and 5-ethoxy-2-pentyloxazole is rapidly converted into the acylamino ester (132) by dilute hydrochloric acid at room temperature (Scheme 4). 

The primary adducts (156) and (157) of oxazoles with alkenes and alkynes, respectively, are usually too unstable to be isolated. An exception is compound (158), obtained from 5-ethoxy-4-methyloxazole and 4,7-dihydro-l,3-dioxepin, which has been separated into its endo and exo components. If the dienophile is unsymmetrical the cycloaddition can take place in two senses. This is usually the case in the reactions of oxazoles with monosubstituted alkynes with alkenes on the other hand, regioselectivity is observed. Attempts to rationalize the orientation of the major adducts by the use of various MO indices, such as 7r-electron densities or localization energies and by Frontier MO theory (80KGS1255) have not been uniformly successful. A general rule for the reactions of alkyl- and alkoxy-substituted oxazoles is that in the adducts the more electronegative substituent R4 of the dienophile occupies the position shown in formula (156). The primary adducts undergo a spontaneous decomposition, whose outcome depends on the nature of the groups R and on whether alkenes or alkynes have been employed. 

The reaction of oxazoles with alkynes is entirely different, leading to furans. The adducts (157) eliminate a cyanide in a retro-Diels-Alder process (equation 15). A typical example is the formation of the ester (164) from 5-ethoxy-4-methyloxazole and dimethyl acety-lenedicarboxylate (equation 16) equation (17) illustrates the production of two regioisomers in this reaction (79MI41802) a more elaborate case is the twofold addition of benzyne to 4-methyl-2,5-diphenyloxazole to give the bridged dihydroanthracene shown in equation (18) (80TL3627). 

Preparation of 5-(3-(2-(5-methyl-2-phenyl-oxazol-4-yl)ethoxy)benzyl)-2-phenyl-4-A-phenylamido-l, 2,3-triazole... 

Oxazol 5-Ethoxy-2-ethoxycar-bonyl-4 methyl- E8a, 928 [ROOC - CH(CH3) - NH -CO-COOR + COCl2] Pentansdure 2,4-Diacetoxy- -nitril V/lc, 252... 

Oxazol 4-Ethoxy-5-isopropyl-5-methyI-4,5-dihydro- El9d, 682 (R —NC + Keton)... 

Methan Pyrrolo-(2-trimethylsilyl-ethoxy)- E14a/2. 162 (Cl -> N) 1,2-Oxazol 3-tert.-Butyl-5-trimethyl-silyl- E8a, 65 [(H3C)3C-CO-C = C —SiR3 4- H2N-OH]... 

Oxazol 5-Ethoxy-2-ethoxycarbonyl-4-(methoxycarbonyl-methyl)- E8a, 928 [ROOC-CH(CH2-COOR) — NH — CO —... 

Oxazol 3-Ethyl-5-[(2-rnethoxy-ethoxy)-methyl]-4,5-dimethyl-... 

Oxazol 5-(4-Brom-phenyl)-4-ethoxy-5-methyl-4,5-dihydro-E19d, 682 (R-NC + Keton)... 

Imidazol 5-Ethoxy-t-hydroxy-2-(2-hydroxy-phenyl)-4-methyl- E8c, 52 [HO — N = C(CH3) — COOC2H5 + Ar—CH = N —OH] Malonaldehydsaure [a-(Hydroxy-methyl)-4-methoxy-benzyliden]- -amid E15/1, 682 (aus 4,5-H2-1,2-oxazol)... 

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