Isoxazole, Nitro

Chlorophenyl)isoxazole 5-(4-N itrophenyllisoxazole 3-(4-Nitrophenyl)isoxazole 3-(4-Chlorophenyl)isoxazole 5-(4-Chloro-3-nitrophenyI)isoxazole 4-Nitro-5-(4-nitrophenyl)isoxazole 4-Nitro-3-(4-nitrophenyl)isoxazole with some 3-(2,4-dinitrophenyl)isoxazole 3-(4-Chloro-3-nitrophenyl)isoxazole 3- (4-Chloro-2-nitrophenyl)isoxazole 4- Nitro-3-(4-chlorophenyl)isoxazole... 

Nitro groups in the homocyclic ring of 1,2-benzisoxazoles have been reduced to the corresponding amino groups without opening of the isoxazole nucleus. SnCU/HCl and Adam s catalyst/H2 have both proved effective in this respect. Similar behavior was observed for nitro groups in the isomeric 2,1-benzisoxazoles (67AHC(8)277,pp.295,33l). 

S612). However, more work is needed to determine its full utility. Table 16 lists the types of isoxazoles synthesized from the condensation of 1,4-dilithio oximes (358) and 2-nitro-acetophenone oximes with electrophiles. 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

Isoxazole, 3,5-dimethyl-3,4-dinitro-quatemization, 6, 21 Isoxazole, 3,5-dimethyl-4-nitro-basicity, 6, 20 reactions, 6, 50... 

Isoxazole, 4-methyI-3,5-diphenyI-bromination, 6, 51 Isoxazole, 3-methyI-4-nitro-5-styryI-photolysis, 6, 14 Isoxazole, 3-methyI-5-phenyl-copper complexes... 

The first electrophilic substitution reaction studied in the isoxazole series was the nitration of 3,5-dimethylisoxazole reported by Morgan and Burgess in 1921.The reaction occurs smoothly on heating with mixed nitric and sulfuric acids at 100°C and leads to the 4-nitro derivative in 86% yield. 

Different results were obtained by Kochetkov and Khorautova. After nitrating 5-phenylisoxazole, they isolated two nitro derivatives, one of which contained a nitro group in the phenyl nucleus, the other one in the isoxazole ring. It is to be expected that the nitration of other phenylisoxazoles results in some second isomer that has not been isolated due to a negligible yield. It will also be noted that the nitration of arylisoxazoles proceeds faster and under milder conditions than necessary for the alkyl derivatives. 

The introduction of electron-accepting substituents into the isoxa-zole nucleus sharply increases its lability toward nucleophilic agents. Thus, whereas isoxazole is cleaved by ethanolic alcoholates, its 4-nitro derivative (131) requires merely heating with aniline for ring... 

A nitro group in the 4-position markedly increases the instability of the isoxazole ring in alkaline medium. This effect is clearly demonstrated by 3,5-dime thy 1-4-nitroisoxazole. Whereas 3,5-dimethyl-isoxazole is not affected by alkali, its 4-nitro-derivative (134) is cleaved by 2% sodium hydroxide. The structure of the product was proved by its conversion into a triazole (135) with phenyl diazonium chloride, according to the original authors. ... 

Although the unsaturated nitrile oxides 124 can be prepared via the aldoxime route (see Scheme 8), the older procedure suffers from the disadvantage that a tenfold excess of allyl alcohol and two additional steps are required when compared to Scheme 15. Therefore, unsaturated nitro ether 123 that can be prepared by condensation of an aldehyde 120 and a nitro alkane followed by Michael addition of alcohol 122, was a useful precursor to nitrile oxide 124 [381. The nitrile oxide 124 spontaneously cyclized to ether 125. This procedure is particularly suitable for the synthesis of tetrahydrofurans (125a-h) and tetrahydropyrans (125i-k) possessing Ar substituents in 72-95% yield (Table 12). The seven-membered ether 1251 was obtained only in 30% yield on high dilution. The acetylenic nitro ether 126 underwent INOC reaction to provide the isoxazole 127. 

Abbreviations N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), L(+)-2 amino-3-phosphonopropionic acid (L-AP3), 6-cyano-7-nitroqninoxaline (CNQ5Q, 2,3-dihydroxy-6-nitro-7-sulfamyl-benzo-f-quinoxaline (NBQX), 3-(2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid (CPP), 7 Chlorokynnreic... 

Primary nitro compounds are good precursors for preparing nitriles and nitrile oxides (Eq. 6.31). The conversion of nitro compounds into nitrile oxides affords an important tool for the synthesis of complex natural products. Nitrile oxides are reactive 1,3-dipoles that form isoxazolines or isoxazoles by the reaction with alkenes or alky nes, respectively. The products are also important precursors for various substrates such as P-amino alcohols, P-hydroxy ketones, P-hydroxy nitriles, and P-hydroxy acids (Scheme 6.3). Many good reviews concerning nitrile oxides in organic synthesis exist some of them are listed here.50-56 Applications of organic synthesis using nitrile oxides are discussed in Section 8.2.2. 

As discussed in Section 6.2, nitro compounds are good precursors of nitrile oxides, which are important dipoles in cycloadditions. The 1,3-dipolar cycloaddition of nitrile oxides with alkenes or alkynes provides a straightforward access to 2-isoxazolines or isoxazoles, respectively. A number of ring-cleaving procedures are applicable, such that various types of compounds may be obtained from the primary adducts (Scheme 8.18). There are many reports on synthetic applications of this reaction. The methods for generation of nitrile oxides and their reactions are discussed in Section 6.2. Recent synthetic applications and asymmetric synthesis using 1,3-dipolar cycloaddition of nitrile oxides are summarized in this section. 

This method gives a somewhat tower yield than method 1. Dissolve 14.1 g l-nitro-3-butanone in 30 ml glacial acetic acid and heat to 35° add slowly with stirring to a solution of 5.3 g bromine in 10 ml glacial acetic acid. Evaporate in vacuum, dissolve residue in ether and wash with water, NaHC03 and water. Dry and evaporate in vacuum the ether (can distill 84/2) to get 6 g 1 -nitro-4-Br-3-butanone (1). Add 4.4 g (I) to 25 ml 48% HBr and reflux three hours. Add 50 ml water and steam distill. Neutralize the distillate with K carbonate and extract with ether. Dry and evaporate the extract (can distill 128/20) to get 5.6 g 2-Br-5-Br-methyl-isoxazole... 

The first demonstration of fluorous synthesis was in the preparation of small (8-12 members) isoxazo-line and isoxazole libraries by the three-step procedure outlined in Figure 8.1461 All reactions were purified by three-phase liquid-liquid extraction. The starting substrates were simple allylic alcohols which were tagged with the fluorous silyl halide 5 to make substrates 6 for an ensuing dipolar cycloaddition. This was conducted by the Mukaiyama method with a large excess of nitro compound and... 

The electron impact mass spectra of 3-methyl-4-nitro-5-styryl-isoxazoles exhibit, on the contrary, only negligible loss of OH"80. This has been interpreted in terms of an isoxazole-to-azirine rearrangement80. The latter fragments directly to an abundant cinnamoyl ion as well as rearranges to oxazole and an epoxide through an intramolecular oxidation of the ethylenic bond by the nitro group80 see Scheme 10. 

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