Isoxazolone

The isoxazolecarboxylic acids are the most intensively investigated of the isoxazole derivatives, and a detailed compilation of their physiochemical properties has been made 62HC(17)l,p. 177). Similar studies have also been carried out with the 5-isoxazolones (62HC(17)l,p. 124), and pK values of 1,2-benzisoxazole derivatives are listed in Table 4. 

The following reaction sequence provides a regiospecific route to 3,4-disubstituted 5-isoxazolones (328) (73ACS2802). The /3-ketoesters (325) were heated under reflux with benzylamine in benzene in the presence of molecular sieves (3 A) to give the )3 -benzylamino-a,)3-unsaturated esters (326). The latter reacted first with hydroxylamine hydrochloride in... 

Chloro- and 5-bromo-isoxazoles have been prepared by reaction of 5-isoxazolones with the appropriate phosphoryl halide (77JMC934). 3-Phenyl-5-trifluoromethylisoxazole has been synthesized by reaction of benzonitrile iV-oxide with 3,3,3-trifluoropropyne (77JMC934). 

In 2000, an efficient three-step procedure for the synthesis of 5-substituted 3-isoxazolols (without formation of undesired 5-isoxazolone byproduct) was published. The method uses an activated carboxylic acid derivative to acylate Meldrum s acid, which is treated with A,0-bis(ten-butoxycarbonyl)hydroxylamine to provide the N,0-di-Boc-protected P-keto hydroxamic acids 14. Cyclization to the corresponding 5-substituted 3-isoxazolols 15 occurs upon treatment with hydrochloric acid in 76-99% yield. 

Benzenediamine (365) and 3-phenyl-4,5-dihydro-5-isoxazolone (366) gave 2-phenylquinoxaline (368), probably via the tetrahydro intermediate (367) (MeCN, reflux, 4 h 65%) " " several substituted-phenyl analogs were prepared similarly and in comparable yields." " When an unsymmetrically substituted benzenediamine was used, two isomeric products were expected, but only one could be detected in each such case tried." " ... 

Although the synthesis of 3-isoxazolols from P-keto esters and hydroxylamine suffers from the formation of 5-isoxazolones as major products, treatment of acyl chlorides with Meldrum s acid 4 followed by aminolysis gave rise to p-keto hydroxamic acids 6 that cyclised to the corresponding 5-substituted 3-isoxazolols 7 without formation of any byproduct <00JOC1003>. Cyclisation of N-substituted salicylhydroxamic acids 9 under... 

Pyrazolone 5(4//)-Pyrazolone 4-Isoxazoline 4(5//)-Isoxazolone 4-Thiazolone 4(5//)-Thiazolone 9-Acridone 9(10//)-Acridone ... 

The heating of N-hydroxy-/V-phenylaminomethylenemalonate (300) in dioxane or cyclohexane for 2 hr, or in the melt at 140°C, afforded 5-isoxazolone (1321, R = Ph) in 60-90% yields (24JCS1456 63TL1365 65T2735). 5-Isoxazolones (1321, R = Ph, 4-MePh, PhCH2) were also pre-... 

Methylisoxazole, 1468 3-Phenyl-5-isoxazolone, 3122 See other gas evolution incidents, n-o compounds... 

It was reported in 1977 that reaction of 3-phenyl-5-isoxazolone with excess of POCI3 in DMF under Vilsmeier conditions gave the isoxazoline 1. Treatment of 1 with MeOH/NaOMe and with 10% NaOH solution was claimed to give the aldehyde 2 and the azirine 3 respectively. 

Subsequent attempts to repeat this work failed. Instead, reaction of 3-pbenyl-5-isoxazolone with POCI3/DMF, first at room temperature then for 30 minutes at 60°C, gave the isoxazolone 4 in 35% yield after standard aqueous quench and neutralisation with 5% NaHC03 solution. When longer reaction times were employed, or when the reaction temperature was raised to 80°C, the product, isolated in 71% yield, was the 1,3-oxazinone 5, and 4 was shown to be the precursor to 5. 

Thakur, P Veeraraghavan, R. Mohapatra, P.K. Manchanda,V.K. Dash, K.C. Extraction of ternary complexes of thorium(IV) with 3-phenyl-4-benzoyl-5-isoxazolone and neutral donors from nitric acid medium, Talanta 43 (1996) 1305-1312. 

Banerjee, S. Bhattacharya, A. Mohapatra, P.K. Basu, S. Manchanda, V.K. Extraction of the uranyl ion with 3-phenyl-4-benzoyl-5-isoxazolone (HPBI) and neutral donors from dilute nitric acid medium, Radiochim. Acta 91 (2003) 729-736. 

Phenyl-5-isoxazolone, 3116a Phenyllithium, 2252 Phenylmagnesium bromide, 2218... 

Phenyl-5-isoxazolone, 3116 Al-Phenylhydroxylamine, 2349 Phenylhydroxylaminium chloride, 2359 Potassium 1-phenylethanediazoate, 2959... 

Phenyl-6-acetylisoxazolo[4,5-fiT]-1,2,3-triazole (47), prepared under mild conditions, was unstable in acid solution and changed rapidly to 3-phenyl-4-diazo-5-isoxazolone (48). The mechanism proposed for cleavage of the triazole ring is outlined in Scheme 6 <70T1393>. 

C-Acetylformamido)-4-isopropyl-3-methyl-4,5-dihydro-5-isoxazolone (55) gave 6-isopropyl-3,5-dimethyl-2 (1 //)-pyrazinone (56) [Lindlar catalyst (Pd/CaC03/trace Pb), H2, EtOH, 20°C, 10 h 90%] also several homologues likewise and in comparable yields.227... 

The next category of f)-diketones are 4-acyl-l-phenyl-3-methyl-5-pyrazolones (see Eigure 2.5) and their analogs of 3-phenyl-4-acyl-5-isoxazolones (see Eigure 2.6). The latter type of P-diketones have stronger acidities (lower pA a values) than the former, and have recently been smdied as promising light conversion molecular devices [46-51]. 

Figure 2.6 Molecular structures of 3-phenyl-4-acyl-5-isoxazolones.

Figure 2.20 Asymmetric unit of complexes Tb(L )3(H20)2, thermal ellipsoids drawn with 30% probability and hydrogen atoms omitted for clarity [51a], (Reproduced from S. Iju, M.L.P. Reddy, A.H. Cowley and K.V. Vasudevan, 3-Phenyl-4-acyl-5-isoxazolonate complex of Tb + doped into poly-P-hydroxybutyrate matrix as a promising light-conversion molecular device, Journal of Materials Chemistry, 19, 5179-5187, 2009, by permission of the Royal Society of Chemistry.)...

Figure 2.22 Asymmetric unit of complex Eu(L )3(DPEPO). Thermal ellipsoids are shown at the 30% probability level and all hydrogen atoms have been omitted for clarity [51c]. (Reprinted with permission from S. Biju, M.L.P. Reddy, A.H. Cowley and K.V. Vasudevan, Molecular ladders of lanthanide-3-phenyl-4-benzoyl-5-isoxazolonate and bis(2-(diphenylphosphino)phenyl) ether oxide complexes the role of the ancillary ligand in the sensitization of Eu + and Tb + luminescence, Crystal Growth and Design, 9, 3562-3569, 2009. 2009 American Chemical Society.)...

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