Aromatic Amines and Nitro-Compounds

Felice et al used a GCE (+0.7 to +0.9 V vs Ag/AgCl) in the analysis of polycyclic aromatic amines, such as 2-aminonaphthalene, 4-aminobiphenyl, and 2-aminoanthracene, in rodent skin samples after topical application of these compounds. The HPLC system used consisted of an ODS-modified silica column with acetonitrile-aq. citrate/perchlorate buffer (7 + 3 or thereabouts) as eluent - the buffer composition and the proportion of acetonitrile were varied in different experiments. A LoD of 0.1 pmol on column could be expected. 

Heterocyclic aromatic amines, such as 2-amino-3-methylimidazo(4,5-f)quinoline, arise from amino acids, proteins, etc. during cooking. Billedeau et al used a short-chain alkyl-modified (SynChropak SCD-100) analytical column and ED (GCE, +0.6-0.9 V vs Ag/AgCl) in the analysis of these compounds. The eluent was acetonitrile-aq. ammonium acetate (50 mmol L pH 5.5-6.5) (25 + 75). No results of sample analyses were reported, however. 

Nitrated polycyclic aromatic hydrocarbons, such as 1-nitropyrene, 1-nitrosopyr-ene and 1,3-dinitropyrene, have been measured in car exhaust deposits by HPLC with chemiluminescence detection after on-line EC reduction (PGEs, —1.6 V vs Pd). LoDs of fmol on-column were claimed. 

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Haefrifiaga P. DetenniiutioD of Nanogram Amounts of Primary Aromatic Amines and Nitro Compounds in Blood and Plasma , J. Chromatogr. 1975, 111, 323-329. 

Grob RL, Cao KB. 1990. High-performance liquid chromatographic study of the recovery of aromatic amine and nitro compounds from soil. J Environ Sci Health Part A Environ Sci Eng... 

Formation of charge-transfer complexes between aromatic amines and nitro-compounds is well known. Compound [77] undergoes an interesting photorearrangement to give [78] (Mutai and Kobayashi, 1981). The reactivity... 

Obsolete uses of urea peroxohydrate, as a convenient source of aqueous hydrogen peroxide, include the chemical deburring of metals, as a topical disinfectant and mouth wash, and as a hairdresser s bleach. In the 1990s the compound has been studied as a laboratory oxidant in organic chemistry (99,100). It effects epoxidation, the Baeyer-Villiger reaction, oxidation of aromatic amines to nitro compounds, and the conversion of sodium and nitrogen compounds to S—O and N—O compounds. 

Aromatic amines, Sulfuric acid Nielsen, A. T. etal., J. Org. Chem., 1980, 45, 2341-2347 The acid, prepared from 90-98% hydrogen peroxide and oleum or 100% sulfuric acid, is one of the most powerful known oxidants and its use for oxidising aromatic amines to nitro compounds has been studied. Some mono- di- and tri-amines are destroyed exothermically with violent fume-off. Precautions for use are detailed. 

Primary, secondary and tertiary aliphatic amines are efficiently converted to nitro compounds in 80-90 % yield with dimethyldioxirane, a reagent prepared from the reaction of oxone (2KHSO5-KHSO4-K2SO4) with buffered acetone. Dimethyldioxirane (DMDO) has been used for the synthesis of 1,3,5,7-tetranitroadamantane (71) from the corresponding tetraamine as the tetrahydrochloride salt (70) and is an improvement over the initial synthesis using permanganate anion (Table 1.7). ° Oxone is able to directly convert some aromatic amines into nitro compounds. 

Secondary alcohols have been oxidized to ketones with excess ferf-butylhydroperoxide in up to 93-99% yields using a zirconium catalyst.250 Zirconium catalysts have also been used with ferf-butylhydroperoxide in the oxidation of aromatic amines to nitro compounds and of phenols to quinones. Allylic oxidation of steroids in 75-84% yields has been performed with ferf-butylhydroperoxide and cop-... 

Oxidation of aromatic amines to nitro-compounds is not normally required. However, in the case of deactivated molecules or in order to obtain specific substitution patterns, this transformation may be useful. The reaction can be carried out by peracids [179], and is readily achieved by the sodium perborate/acetic acid system, in the absence of metal catalysts [180]. Less forcing conditions with peracids can be used to make nitroso-compounds [181]. However, the use of a low excess of oxidant, or of conditions where reaction is slow, encourages coupling of the nitroso-compound with unreacted amine to give a diazo-compound. This can be made deliberately as the major product [182], and will itself undergo further oxidation to the azoxy-compound, which is then hard to oxidise further [183]. 

Grirrane, A., Corma, A. and Garcia, H. (2010). Preparation of Symmetric and Asymmetric Aromatic Azo Compounds from Aromatic Amines or Nitro Compounds Using Supported Gold Catalysts, Nature Protocols, 5, pp. 429-438. 

By oxidation, aromatic amines and nitroso compounds may be converted to nitro compounds. 

In general, peroxomonosulfates have fewer uses in organic chemistry than peroxodisulfates. However, the triple salt is used for oxidizing ketones (qv) to dioxiranes (7) (71,72), which in turn are useful oxidants in organic chemistry. Acetone in water is oxidized by triple salt to dimethyldioxirane, which in turn oxidizes alkenes to epoxides, polycycHc aromatic hydrocarbons to oxides and diones, amines to nitro compounds, sulfides to sulfoxides, phosphines to phosphine oxides, and alkanes to alcohols or carbonyl compounds. 

Although this reduction is more expensive than the Bnchamp reduction, it is used to manufacture aromatic amines which are too sensitive to be made by other methods. Such processes are used extensively where selectivity is required such as in the preparation of nitro amines from dinitro compounds, the reduction of nitrophenol and nitroanthraquinones, and the preparation of aminoazo compounds from the corresponding nitro derivatives. Amines are also formed under the conditions of the Zinin reduction from aromatic nitroso and azo compounds. 

Aromatic hydrocarbons can be purified as their picrates using the procedures described for amines. Instead of picric acid, 1,3,5-trinitrobenzene or 2,4,7-trinitrofluorenone can also be used. In all these cases, following recrystallisation, the hydrocarbon can be isolated either as described for amines or by passing a solution of the adduct through an activated alumina column and eluting with toluene or petroleum ether. The picric acid and nitro compounds are more strongly adsorbed on the column. 

These oxidants are generally too feeble to attack monofunctional compounds except thiols, carbonyl- and nitro-compounds in their enolic forms, phenols and aromatic amines. However, ferric rWj-o-phenanthroline readily oxidises cyclohexanone. 

The synthesis of nitro dyes is relatively simple, a feature which accounts to a certain extent for their low cost. The synthesis, illustrated in Scheme 6.5 for compounds 140 and 141, generally involves a nucleophilic substitution reaction between an aromatic amine and a chloronitroaromatic compound. The synthesis of C. I. Disperse Yellow 14 (140) involves the reaction of aniline with l-chloro-2,4-dinitroaniline while compound 141 is prepared by reacting aniline (2 mol) with compound 144 (1 mol). 

The purpose of this book is to emphasize recent important advances in organic synthesis using nitro compounds. Historically, it was aromatic nitro compounds that were prominent in organic synthesis. In fact they have been extensively used as precursors of aromatic amines and their derivatives, and their great importance in industrial and laboratory applications has remained. 

I.2. Oxidation of Amines Oxidation of primary amines is often viewed as a particularly convenient way to prepare hydroxylamines. However, their direct oxidation usually leads to complex mixtures containing nitroso and nitro compounds and oximes. However, oxidation to nitrones can be performed after their conversion into secondary amines or imines. Sometimes, oxidation of secondary amines rather than direct imine oxidation seems to provide a more useful and convenient way of producing nitrones. In many cases, imines are first reduced to secondary amines which are then treated with oxidants (26). This approach is used as a basis for a one-pot synthesis of asymmetrical acyclic nitrones starting from aromatic aldehydes (Scheme 2.5) (27a) and 3,4-dihydroisoquinoline-2-oxides (27b). 

Some Aromatic Amines and Related NItro Compounds—Hair Dyes, Colouring Agents and Miscellaneous Industrial Chemicals 1978 400 pages... 

A very flexible method of preparing unsymmetrical azo compounds makes use of the condensation of C-nitroso compounds with amines. Thionylamines have also been condensed with substituted hydroxylamines to produce azo compounds not usually accessible by other means. Treatment of dialkylsulfuric diamides with sodium hypochlorite is one means of preparing aliphatic azo compounds. Aromatic amines and aromatic nitro compounds at high temperature produce azo compounds. 

Fortunately, there is now a comprehensive body of knowledge on the metabolic reactions that produce reactive (toxic) intermediates, so the drug designer can be aware of what might occur, and take steps to circumvent the possibility. Nelson (1982) has reviewed the classes and structures of drugs whose toxicities have been linked to metabolic activation. Problem classes include aromatic and some heteroaromatic nitro compounds (which may be reduced to a reactive toxin), and aromatic amines and their N-acylated derivatives (which may be oxidized, before or after hydrolysis, to a toxic hydroxylamine or iminoquinone). These are the most common classes, but others are hydrazines and acyl-hydrazines, haloalkanes, thiols and thioureas, quinones, many alkenes and alkynes, benzenoid aromatics, fused polycyclic aromatic compounds, and electron-rich heteroaromatics such as furans, thiophenes and pyrroles. 

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