Nitro compounds nitronic acids

Nitro compounds have been converted into various cyclic compounds via cycloaddidon reactions. In particular, nitroalkenes have proved to be nsefid in Diels-Alder reactions. Under thermal conditions, they behave as electron-deficient alkenes ind react v/ith dienes to yield 3-nitrocy-clohexenes. Nitroalkenes c in also act as heterodienes ind react v/ith olefins in the presence of Lewis acids to yield cyclic alkyl nkronates, which undergo [3- 2 cycloaddidon. Nitro compounds are precursors for nitnie oxides, alkyl nitronates, and trialkylsilyl nitronates, which undergo [3- 2 cycloaddldon reacdons. Thus, nitro compounds play important roles in the chemistry of cycloaddidon reacdons. In this chapter, recent developments of cycloaddinon chemistry of nitro compotmds and their derivadves are summarized. 

The nitro form is much more stable than the aci form in sharp contrast to the parallel case of nitroso-oxime tautomerism, undoubtedly because the nitro form has resonance not found in the nitroso case. Aci forms of nitro compounds are also called nitronic acids and azinic acids. 

The condensation of nitro compounds and imines, the so-called aza-Henry or nitro-Mannich reaction, has recently emerged as a powerful tool for the enantioselective synthesis of 1,2-diamines through the intermediate /3-amino nitro compounds. The method is based on the addition of a nitronate ion (a-nitro carbanion), generated from nitroalkanes, to an imine. The addition of a nitronate ion to an imine is thermodynamically disfavored, so that the presence of a protic species or a Lewis acid is required, to activate the imine and/or to quench the adduct. The acidic medium is compatible with the existence of the nitronate anion, as acetic acid and nitromethane have comparable acidities. Moreover, the products are often unstable, either for the reversibility of the addition or for the possible /3-elimination of the nitro group, and the crude products are generally reduced, avoiding purification to give the desired 1,2-diamines. Hence, the nitronate ion is an equivalent of an a-amino carbanion. 

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

X,P-Dehydro-a-amino acids are prepared by elimination of HN02 from P-nitro-a-amino acids, which are prepared by reaction of a-bromoglycine derivatives with alkyl nitronates (see Eq. 7.135).181 This process is a new type of the Michael addition of nitro compounds followed by elimination of HNOz. Such unusual amino acids are interesting as enzyme inhibitors.182... 

Alternatively, Ballini devised a new strategy to synthesize tri-alkylated pyrroles from 2,5-dialkylfurans and nitroalkanes <00SL391>. This method involves initial oxidation of 2,5-dimethylfuran with magnesium monoperoxyphthalate to cA-3-hexen-2,5-dione (6). Conjugate addition of the nitronate anion derived from the nitro compound 7 to 6 followed by chemoselective hydrogenation of the C-C double bond of the resulting enones 8 (obtained by elimination of nitrous acid from the Michael adduct) completes the conversion to the alkylated y-diketones 9. Final cyclization to pyrroles 10 featured improved Paal-Knorr reaction conditions involving reaction of the diketones with primary amines in a bed of basic alumina in the absence of solvent. 

I. Condensation of N-Monosubstituted Hydroxylamines with Carbonyl Compounds Condensation of N -monosubstituted hydroxylamines with carbonyl compounds is used as a direct synthesis of many acyclic nitrones. The synthesis of hydroxylamines is being carried out in situ via reduction of nitro compounds with zinc powder in the presence of weak acids (NH4CI or AcOH) (14, 18, 132). The reaction kinetics of benzaldehyde with phenylhydroxylamine and the subsequent reaction sequence are shown in Scheme 2.21 (133). 

As can be seen from Scheme 3.88, nitrile oxides can be generated in the reactions of acids or bases with other alkyl nitronates derived from a-functionalized nitro compounds (300, 301). 

The reactions of salts of nitro compounds (113) (Scheme 3.95) with silylated thiols (308), hexamethyldisilathiane (308, 309), and hexamethyldisilane (310) afford oximes (114), thiohydroxamates (115), or thiohydroxamic acids (116) as final products depending on the structures of the starting nitronates and the reagents used. 

E. Brener, Nitrones and Nitronic Acid Derivatives Their Structure and their Roles in Synthesis , in The Chemistry of Amino, Nitroso and Nitro Compounds and their Derivatives, Vol. 1, S. Patai ed., Wiley, Chichester, 1982, pp. 459-538. 

The Soft Nef-Reaction was carried out with different nitronate ions 44 and different buffers as shown in Table 2 [38]. As expected the use of p-toluenesulfonic acid (48) alone resulted in the formation of the Nef-products 47 whereas pyridine (50) and 2,6-dimethylpyridine (51) buffers gave the nitro compounds 45. 

Table 2. Competition between C-protonation (formation of nitro compounds 45) and O-proton-ation (formation of the Nef-product 47) in the protonation of nitronate ions 44 (s. Scheme 8). The percentage of C-protonated product 45 for different buffers (pyridine/p-toluenesulfonic acid) and unbuffered p-toluenesulfonic acid (48) is listed...

Nitro-compounds fRNOj) are isomeric with nitrites, but their electronic structure, excited states and photochemistry are very different. There is no very low-lying (n.jt ) state, and nitroalkanes show n — 3i absorption with a maximum around 275 nm ( —201 mol - cm In cyclohexane solution, nitromethane (CH1NOi) is photoreduced to nitrosomethane(CH,NO, but nitroethane under the same conditions gives rise to a nitroso-dimer derived from the solvent CS.47). The latter process is probably initiated by cleavage of the carbon-nitrogen bond in the nitroalkane. In basic solution (when the nitroalkane is converted to a nitronate anion) irradiation can lead to efficient formation of a hydroxamic acid (S.48), and this reaction most likely proceeds through formation of an intermediate three-mem bered cyclic species. 

It was also reported that diastereo- and enantioselective Mannich reactions of activated carbonyl compounds with a-imino esters were catalyzed by a chiral Lewis acid derived from Cu(OTf)2 and a bisoxazoline (BOX) ligand [31] [(Eq. (6)]. Catalytic enantioselective addition of nitro compounds to imines [32], and aza-Henry reactions of nitronates with imines [33] also proceeded under similar reaction conditions. 

CHN01 - C=0. This transformation can be effected by treatment with base to generate the nitronate anion followed by oxidation with Mo05 Py HMPT. Primary nitro compounds under these conditions are converted to carboxylic acids via an aldehyde. This method is an alternative to the Nef reaction.2... 

The conversion of nitro compounds into carbonyls is known as the Nef Reaction. Various methodologies have been developed, but the most important is the standard procedure a preformed nitronate salt is poured into strong aqueous acid (pH < 1). Some oxidative variations have also found wide application, and some reductive methods have even been developed. 

Nitro = ac/-nitro tautomerism occupies a special role as it has been speculated to occur under conditions where high energy explosives detonate. It has been proposed as one of the important initial steps responsible for the cascade of reactions leading to the high energy release during detonation [1], Nitro = aci-nitro tautomerism in nitro compounds RjCH-NO leads to nitronic acids, R2C=N(0)OH. Kinetic studies show similar pKa values for nitronic acids and their carbon counterparts, the carboxylic acids [1]. Nitroalkane = nitronic acid tautomerism has been assumed not to be an acid-catalyzed process because of the poor basicity of N02 group [4]. However, recent work by Erden et al. showed that this tautomerism can, in fact, be achieved under acid catalyzed... 

Nitronic acids are stabilized by inter- and intramolecular hydrogen bonding. Kang et al. [6b] showed that nitro compound 4 is slowly, but spontaneously converted to nitronic acid tautomer 4t due to the stabilization that results from... 

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