Nitriles from nitroalkanes

The anions derived from nitroalkanes, ketones, esters, and nitriles react with p-dinitroben-zene to give the corresponding products, as shown in Eq. 9.12 and Eq. 9.2.3... 

The other method starts from nitroalkanes and is a dehydration. Inspect the two molecules and you will see that the nitro compound contains H2O more than the nitrile oxide. But howto remove the molecule of water The reagent usually chosen is phenyl isocyanate (Ph-N=C=0). which removes the molecule of water atom by atom to give aniline (PhNHa) and C02. This is probably the mechanism, though the last step might not be concerted as we have shown. 

Nitriles. Primary nitroalkanes are converted to nitriles with this reagent combination in the presence of triethylamine. Conjugated nitriles are formed more rapidly from allylic nitroalkenes. 

Nitrile oxides could also be prepared from nitroalkanes by reaction with (Boc)20 in the presence of catalytic amounts of DMAP at room temperature under N2 [276]. Alternatively they could also be prepared via base-induced dehydrohalogenation from hydroximinoyl chlorides, which can be either purchased or generated hy chlorination of the corresponding aldoximes with N-chlorosucdnimide. 

The reagent DMTMM has been used also for the generation of nitrile oxides in situ from nitroalkanes under very mild conditions using microwave irradiation. The reaction requires the presence of 4-dimethylaminopyridine (DMAP) as catalyst (Scheme 66). 

In this volume we present five selected contributions by well-known authors, each an authority in his field. The first chapter deals with construction of isoxazolines (dihydroisoxazoles) via 1,3-dipolar cycloadditions of nitronates or of nitrile oxides generated from nitroalkanes. This includes inter- as well as intramolecular processes. Many of these heterocycles possess important synthetic and biological properties and are shown to lead to stereo- and re-gioselective introduction of multifunctional molecules such as amino alcohols, )6-amino acids, aldols, nitriles, and others. 

Isoxazole-isoxazoline polyheterocyclic systems have been synthesized for applications as ionophores using resin boimd alkenes/alkynes as dipo-larophiles. For instance, the isoxazole possessing an alkene moiety 41 was reacted with a nitrile oxide, generated from nitroalkane 13d imder Mukaiyama conditions, to afford isoxazoline 42 in high yield (Scheme 12) [ 104]. 

Zhao and co-workers reported a regioselective cycloaddition of nitrile oxide generated from nitroalkane 13f with N-vinyl bases 43 to generate nude-... 

When nitrile oxide 5g, generated in situ from nitroalkane 13g, was reacted with diethyl fumarate and diethyl maleate 46, stereospecific cycloaddition took place to afford the adducts 47 in 35% and 60% yield, respectively (Scheme 14) [108]. However, when presynthesized nitrile oxide 5g was used, the yields improved to 98% and 93%, respectively. 

As part of their solid- and solution-phase synthesis of novel hydantoin-isoxazoline containing hetero cycles, Kurth and co-workers reacted solid supported urea intermediates 48, possessing an alkene moiety with nitrile oxides derived from nitroalkanes 13a and 13d to afford isoxazolines 49 as a 1 1 mixture of diastereomers (Scheme 15) [109]. The urea fimctionality in 49 was then cyclized to obtain hydantoin 50. 

Giacomelli et al. have generated nitrile oxides from nitroalkanes 13 using DMTMM (4-(4,6-dimethoxy[ l,3,5]triazin-2-yl)-4-methylmorpholinium chloride) 70 as the dehydrating agent in the presence of DMAP in acetonitrile and reacted them with alkenes 68 to afford isoxazolines 69 (Scheme 21) [88]. The authors found microwave irradiation conditions to be superior to the conventional room temperature method. 

Both the chiron and the auxiliary approaches have been adopted for developing the asymmetric versions of intermolecular 13DC of nitrile oxides generated from nitroalkanes as described below. To our knowledge, the corresponding catalytic approach remains obscure. 

Nitronates, particularly silyl nitronates, are often superior to nitrile oxides in their 13DC with olefins in terms of their ease of generation from nitroalkanes, stability, and the observed selectivity during cycloaddition. Cycloaddition of alkyl or silyl nitronates with olefins generates N-alkoxy- or N-silyloxy-substituted isoxazolidines which then undergo spontaneous or acid catalyzed elimination of alcohol (or silanol) to produce isoxazolines (see Scheme 1, Sect. 2). 

Enantioselective synthesis of N-protected aminodiols 235 and 239 via dia-stereoselective inter- and intramolecular cycloaddition of optically active nitrile oxides 233 and 237 followed by cleavage of the isoxazoHnes 234 and 238 has been reported by Enders and co-workers (Schemes 55 and 56) [156]. The nitrile oxides 233 and 237 were generated from nitroalkanes 232 and 236, respectively, which in turn were obtained by diastereoselective oxa-Michael addition of (IR, 2S)-(-)-N-formylnorephedrine 231 to ahphatic nitroalkenes 75b,c. The LiAIH4-mediated cleavage of isoxazolines 234 and 238 to aminoal-cohols 235 and 239, respectively, proceeded with >96% diastereoselectivity. 

Oh and co-workers utilized nitrile oxide cycloaddition chemistry for the preparation of 4-oxo-2-alkenylphosphonates 247 by y-acylation of allyhc phosphonates 244 (Scheme 58) [158,159]. Regioselective dipolar cycloaddition between nitrile oxides obtained from nitroalkanes 13 and allylic phosphonates 244 serving as dipolarophiles provided phosphonate-containing 2-isoxazolines 245 in good yields. Isoxazolines 245 upon LDA-mediated ring cleavage followed by hydrolysis of the corresponding oximes 246 yielded 4-oxo-2-alkenylphosphonates 247. 

Cyclization is known to release resin-bound compounds without a linker. Hydantoin ring formation releases resin-bound compounds smoothly, producing interesting hydantoin derivatives with potential medicinal or biological activity. Resin-bound alkenes reacted with nitrile oxides that were generated with Mukaiyama s method from nitroalkane (Scheme 11.48). The isoxazolines were cleaved from the resin via ahydantoin formation upon heating under basic conditions. 

Solid-supported isoxazoles were obtained from resin-bound alkynes and nitrile oxides generated in situ from nitroalkanes and isocyanate (Scheme 11.50). The isoxazoles were cleaved from the resin via hydantoin formation upon heating and 18 diverse products were obtained in high purities. 

Nitronates derived from primary nitroalkanes can be regarded as a synthetic equivalent of nitrile oxides since the elimination of an alcohol molecule from nitronates adds one higher oxidation level leading to nitrile oxides. This direct / -elimination of nitronates is known to be facilitated in the presence of a Lewis acid or a base catalyst [66, 72, 73]. On the other hand, cycloaddition reactions of nitronates to alkene dipolarophiles produce N-alkoxy-substituted isoxazolidines as cycloadducts. Under acid-catalyzed conditions, these isoxazolidines can be transformed into 2-isoxazolines through a ready / -elimination, and 2-isoxazolines correspond to the cycloadducts of nitrile oxide cycloadditions to alkenes [74]. 

The photochemical cyclisation of p.y-unsaturated ketoximes to 2-isoxazolines, e.g., 16—>17, has been reported <95RTC514>. 2-Isoxazolines are obtained from alkenes and primary nitroalkanes in the presence of ammonium cerium nitrate and formic acid <95MI399>. Treatment of certain 1,3-diketones with a nitrating mixture generates acyl nitrile oxides, which can be trapped in situ as dipolar cycloadducts (see Scheme 3) <96SC3401>. 

In 1970, a new reaction, the displacement of a nitro group from a-nitro esters, a-nitro nitriles, a-nitro ketones, and a,a-dinitro compounds by nitroalkane salts, was described.3 These displacements, which are exemplified by the reaction presented in Eq. 7.1, take place at room temperature and give excellent yields of pure products. The reaction proceeds via a radical chain mechanism involving one electron-transfer processes as shown in Scheme 7.1 the details of the mechanism are described in a review.1... 

Highly efficient modifications of Mukaiyama s procedure, convenient for combinatorial syntheses, were reported recently, namely the polymer-supported synthesis of isoxazolines via nitrile oxides, starting from primary nitroalkanes, in a one-pot process (75) and by microwave activation of the process (73). 

The intermediate Michael adducts have been isolated from the reaction of a-chloro-a-nitroalkanes with a, 3-unsaturated aldehydes, ketones, nitriles and esters... 

Isoxazoline derivatives of Cgo such as 250 (Scheme 4.40) are accessible by 1,3-dipolar cycloadditions of nitrile oxides to [6,6] double bonds of the fullerene [2, 278, 291-305]. The nitrile oxides 249 with R = methyl, ethyl, ethoxycarbonyl and anthryl are generated in situ from the corresponding nitroalkane, phenyl isocyanate and triethylamine. The isoxazoline derivative of Cgo 250 (with R = anthryl) crystallizes in black prisms out of a solvent mixture of CS2 and acetone (3 2) [292]. X-ray crystal structure analysis shows that addition of the nitrile oxide occurs on a [6,6] double bond of the fullerene framework. 

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