Preparation of Nitro Compounds

Note If the semimicro method is used, sections (A) and (B) may be run simultaneously. The macro method is given only for nitrobenzene if that method is used for the other preparations the quantities given for the semimicro methods should be increased proportionately. 

Introduction. The replacement of hydrogen atoms by nitro groups in organic compounds takes place easily by direct nitration in aromatic compounds. Although aliphatic nitro compounds are produced industrially by nitration in the vapor phase, the rates of nitration in aromatic compounds at temperatures below 100° are such as to be usually regarded as one of the chief differences from the aliphatic. 

Aryl nitro compounds are easily prepared by the action of a mixture of nitric and sulfuric acids at 50-60°. If nitration is diflS-cult, a mixture of potassium nitrate and sulfuric acid is employed in other cases, as in the introduction of a second nitro group, a mixture of fuming nitric and fuming sulfuric acids is used. In nitration, water is one of the products of the reaction  

The function of sulfuric acid in nitrations is to absorb the water formed, thus preventing the dilution of nitric acid. Another useful purpose of sulfuric acid is its solvent property for many organic compoxmds. In some cases the first action of sulfuric acid is to sulfonate. The sulfonic acid groups are subsequently replaced by nitro groups. Due to their insolubility in water, nitro compounds are rather easily separated by dilution of the nitrated mixture. 

Alkyl nitro compounds are not easily prepared by direct nitration. A few, however, can be prepared by direct nitration of the hydrocarbons in the vapor phase at 400°. Most alkyl nitro compounds can be prepared by the action of metallic nitrites on halogen compounds. This reaction also gives some isomeric alkyl nitrites. TTie object of the present experiment is to illustrate the preparation of an aryl nitro compoxmd. 

Cross-linked polystyrene can be directly nitrated with fuming nitric acid at low temperatures (-25 °C to 0°C) [189,203,374] polymers with up to one nitro group per arene result [203]. Partial nitration can be achieved with milder nitrating agents, such as acetyl nitrate [203]. Because direct nitrations are not compatible with most linkers (which are often acid- or oxidant-labile), nitro compounds are generally not prepared on supports but in solution, and are then linked to the support. 

Karoyan, P. Triolo, A. Nannicini, R. Giannotti, D. Altamura, M. Chassaing, G. Perrotta, E. Tetrahedron Lett. 1999,40,71-74. 

Kurokawa, K. Kumihara, H. Kondo, H. Bioorg. Med. Chem. Lett. 2000,10,1827-1830. 

Renault, J. Lebranchu, M. Lecat, A. Uriac, P. Tetrahedron Lett. 2001, 42, 6655-6658. 

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General reviews for preparation of nitro compounds and for the reaction of nitro com-pounds" " are listed in the references. 

Conversion of carbonyl to nitro groups (retro Nef Reaction) is an important method for the preparation of nitro compounds. Such conversion is generally effected via oximes using strong oxidants such as CF3CO3H.120... 

Couplings of nitroalkyl radicals with nucleophiles such as CN-, N, N02, and other nitrogen nucleophiles provides a useful method for the preparation of nitro compounds with such groups at the a-position.49 65 The alkylation of nitromethane with trialkylborane is possible by electrolysis, in which alkyl radicals may be involved (Eq. 5.46).66... 

Nitration with concentrated nitric acid or its mixture with sulphuric acid has already been described and several examples will be given in those chapters dealing with the preparation of nitro compounds. Methods more rarely used which have already been applied in practice or may be in future, are described in this chapter. 

There are several general reviews of this area of chemistry. This section covers mainly novel methods and improvements to established procedures for the preparation of nitro compounds which have been published within the last 10 years. 

Use Preparation of nitro compounds, rocket fuels, laboratory reagent. 

The reaction of phenols with nitrous acid gives the ortho- and para-nitroso products, which are formed through a neutral dienone intermediate, the proton loss from the latter being the rate-limiting step" " . It has been shown that the nitrous acid can act as a catalyst for the formation of the nitro derivatives. Thus the conventional preparation of nitro compounds by the oxidation of nitroso compounds may be replaced by methods using an electron-transfer pathway in certain cases. In the latter method, the phenoxide reacts with nitrosonium ion to give the phenoxy radical and nitric oxide radical. The nitric oxide radical is in equilibrium with the nitronium radical by reaction with nitronium ion. The reaction of the phenoxy radical with the nitroninm radical resnlts in the formation of the ortho- and para-mixo prodncts" . Leis and coworkers carried ont kinetic stndies on the reaction of phenolate ions with alkyl nitrites and fonnd that the initially formed product is the 0-nitrite ester, which evolves by a complex mechanism to give the ortho-and the para-nitro products". ... 

Recently, however, Kornblum et al.651 showed that alkali nitrites, in particular sodium nitrite, can replace silver nitrite in the preparation of nitro compounds if dimethylformamide is used as solvent. The method has the additional advantage that not merely primary but also secondary alkyl iodides and bromides react readily in this solvent. Yields are around 60% in both cases. It usually suffices to stir the halide with an excess of sodium nitrite in dimethylformamide for some hours at room temperature primary iodides need about 2.5 hours, primary bromides about 6 hours for complete reaction. With secondary halides it is advisable to add urea as this raises the solubility... 

Sections 211 to 299 are reserved for future additions (e.g. the preparation of nitro compounds)... 

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