Primary nitro compounds

Primary nitro compound intense red colour, disappearing upon acidification. The colouration is that of the alkali salt of the nitrolic acid (nitro oxime) -... 

TheNef reaction of primary nitro compounds gives iildehydes or carboxylic acids, depending on the reaction conditions. Each transformation provides an important tool in organic synthesis. Primary nitro compotmds are converted into carboxylic acids vrith concentrated mineriil acids. Because such harsh conditions iilso lead to side reactions, a milder method is required inorganic synthesis. Basic phosphate-buffered KMnO rapidly converts primary nitroalkanes into carboxylic acids in 90-99% yield fEq. 6.13. "... 

Photoredncdon of aromadc and aliphadc nitro compounds gives hydtoxylamines or amines, which is well reviewed The radicid reacdon of primary nitro compounds v/ith dn hydnde does not give the denitrated product fsee Chapter 7, but give the corresponding oximes fEq... 

Tertiary nitro compounds are converted into the cortespooding thiols by the reacdon with sodium sulfide and snlfnr fSj in DMSO followed by the redncdon with Al-Hg. fEq. 7.12. Secondary and primary nitro compounds do not give thiols in these reacdons instead, a complex set of product is formed. 

When primary nitro compounds are treated with sulfuric acid without previous conversion to the conjugate bases, they give carboxylic acids. Hydroxamic acids are intermediates and can be isolated, so that this is also a method for preparing them. Both the Nef reaction and the hydroxamic acid process involve the aci form the difference in products arises from higher acidity, for example, a difference in sulfuric acid concentration from 2 to 15.5 M changes the product from the aldehyde to the hydroxamic acid. The mechanism of the hydroxamic acid reaction is not known with certainty, but if higher acidity is required, it may be that the protonated aci form of the nitro compound is further protonated. 

Hydroxamic acids can also be prepared from primary nitro compounds with SeOa and EtsN Sosnovsky, G. Krogh, J.A. Synthesis, 1980, 654. 

Whereas secondary nitroalkanes such as 1-nitrocyclohexane 1766 are reduced to the corresponding oximes, for example 1767 [24], primary nitro compounds such as a-nitro-o-xylene 1768 or unsaturated nitro compounds such as 1770 are transformed into nitriles such as 1769 and 1771 [24] (Scheme 12.6). 

The anion of primary nitro compounds such as nitroethane reacts with hexamethylsilthiane 601 to give acetothiohydroxamic acid 1913 in 81% yield [117], whereas reaction with phenylthiotrimethylsilane 584 affords phenyl acetothiohy-droximate 1914 in 62% yield [117] (Scheme 32.33). Secondary nitro compounds... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Nitro compounds are versatile precursors for diverse functionalities. Their conversion into carbonyl compounds by the Nef reaction and into amines by reduction are the most widely used processes in organic synthesis using nitro compounds. In addition, dehydration of primary nitro compounds leads to nitrile oxides, a class of reactive 1,3-dipolar reagents. Nitro compounds are also good precursors for various nitrogen derivatives such as nitriles, oximes, hydroxylamines, and imines. These transformations of nitro compounds are well established and are used routinely in organic synthesis. 

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. 

A detailed study of the role of the base in the formation of 2-isoxazolines by condensation of primary nitro compounds with alkenes in the presence of the tertiary diamine 1,4-diazabicyclo[2.2.2]octane (DABCO) was published <06EJO4852 06EJ03016>. 

The addition of C-centered radicals to the C=N bond giving rise to radicals B (Scheme 3.98) can be used for organization of radical C-alkylation of primary nitro compounds containing the sulfo group at the a-position (315). 

Nef reaction.4 Nitro compounds, primary or secondary, are converted to tri-alkylsilyl nitronates in greater than 90% yield by reaction with a trialkylsilyl chloride and DBU in CH2C12. The silyl nitronates derived from secondary nitro compounds are oxidized by C1QH4C03H at 25° to ketones in high yield. This sequence is not useful for conversion of primary nitro compounds to aldehydes. 

Like the ketones the primary nitro-compounds condense with aldehydes, water being eliminated. Phenylnitroethylene is conveniently prepared in this way. 

All primary nitro-compounds couple with diazobenzene, but instead of the expected azo-compounds, phenylhydrazones of a-nitro-aldehydes are formed by rearrangement of the molecule ... 

Victor Meyer also discovered the reactions of aliphatic nitro compounds with nitrous acid, which likewise depend on the activation of CH by NO221. Primary nitro compounds give nitrolic acids RC(N02) N0H, secondary nitro compounds give pseudo-nitroles R2C(N0)N02 and tertiary nitro compounds, having no activated CH, do not react. 

Aliphatic nitro compounds exhibit rather different behavior from nitroaromatic compounds. Secondary and primary nitro compounds tend to produce oximes because the intermediate nitroso compound quickly tautomerizes to the oxime (equation 1). Under aprotic conditions the radical anions of primary and secondary nitro compounds are relatively stable those derived from tertiary nitro compounds, on the other hand, eject nitrite ion relatively readily (equation 2)8. 

Generally primary nitro compounds are reduced to aldoximes and secondary to ketoximes by metal salts. On reduction with stannous chloride 1,5-... 

Primary nitro compounds RNO were oxidised to RCOOH (the Nef reaction e.g. nitroethane to acetic acid) [RuO ] from RuCl3/(Br03)7aq. M Na2(C03) activated primary aUcyl halides RCl to RCOOH and secondary alkyl halides were similarly oxidised to ketones [213]. Secondary nitro compounds were converted to ketones by TPAP/NM0/PMS/K3(C03)/CH3CN (c/ 5.6.4, Fig. 5.19) [514]. As part of the total synthesis of the natural product ( )-erythrodiene a nitro-alcohol intermediate was converted to the diketone by TPAP/NMO/PMS/CH Clj [127]. 

T. Urbanski, Synthesis 1974, 613-632 . .Primary Nitro Compounds as a Source of Some Heterocyclic Systems". 

Nitriles can be obtained in one step by treatment of primary nitro compounds with PC13 and pyridine,420 R may be alkyl or aryl and may contain C=C double bonds or various functional groups. Yields are moderate to good. The reaction has also been carried out with Me3N-S02 and with HMPA.421 Primary azides RCH2N3 have been converted to nitriles RCN with Pd metal.422 Primary nitro compounds RCH2N02 were converted to nitrile oxides 0... 

Nitrile oxide J -I- 2 cycloaddition.1 A key step in a recent stereospecific synthesis of biotin (6) from cycloheptene (1) is an intramolecular [3 + 2]cyclo-addition of a nitrile oxide (a), obtained by dehydration of a primary nitro compound (3), preferably with phenyl isocyanate. This cycloaddilion is more efficient than the well-known olefinic nitrone cycloaddition. The carbon atoms in 6 derived from cycloheptene are marked with asterisks. 

Quaternary aldehydes. Tertiary nitro comounds (1) can be converted to primary nitro compounds with a quaternary center (2) by reaction with the sodium salt of nitromethane in the presence of sodium hydride in DMSO (equation I).1... 

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