138 Synthetic Routes to AromaticC-Nitro Compounds
Topchiev^7 has given an extensive discussion of nitrating conditions used, and the products
obtained, for all manner of aromatic substrates.
Polynitroarylenes with unusual substitution patterns and those containing more than three
nitro groups per benzene ring are usually not useful as practical explosives. Many of these
compounds can be synthesized via indirect routes, including: arylamine and arylhydroxylamine
oxidation, treating diazonium salts of arylamines with nitrite anion in the presence of copper
salts, and Ullmann coupling of polynitrohalobenzenes. The latter is useful for the synthesis of
high molecular weight polynitroarylenes (Section 4.10) and partially nitrated biphenyls.
4.3.3 Effect of nitrating agent and reaction conditions on product selectivity
The nature of the substituents presence in an aromatic substrate has a large effect on which
positions are substituted on nitration. The isomeric ratio of products obtained on nitration is
also dependent on the nitration conditions, nitrating agent, nitrating medium and its acidity,
acid composition and concentration etc., but often to a lesser extent.
Substrates containing substituents with nonbonding electrons localized on heteroatoms i.e.
phenol ethers, anilines, substituted anilines, acetanilides etc. often exhibit very large differences
in product isomer ratio with change in nitration conditions. The nitration of such substrates
with mixed acid^68 –^70 often yields higher than expected proportions of theparaisomer, whereas
solutions of nitric acid in acetic anhydride^69 –^71 are usually very selective for the formation of the
orthoisomer. Such results are related to the nature of the nitrating medium, with high selectivity
fororthonitration observed in aprotic solvents and highparaselectivity typical of nitration in
protic solvents. A possible explanation^72 for these observations is that protic solvents, such as
mixed acid, hinderorthoattack by strongly solvating the electron-rich heteroatom via hydrogen
bond type interactions. On the other hand, substrates like phenol ethers and acetamides have
the highest electron density located on the basic heteroatoms, and as such, on electronic
grounds and in the absence of heteroatom solvation, substitution would be favoured at the
orthopositions, and this is usually observed in aprotic solvents.^73 Other possible explanations
and mechanisms have been reported.^8 ,^70 ,^71 ,^73
The localization of electron density on heteroatoms is seen during the nitration of anilines
which areN-nitrated in aprotic media.^74 Anilines can give abnormalo/p-isomer ratios resulting
from a process ofN-nitration followed by rearrangement to the ring nitrated product, a process
which often occursin situin the strongly acidic medium of mixed acid (Section 4.5).
The nitration of phenols can result in anomalous and large differences in product isomer
ratios, showing a high dependence on both nitrating agent and reaction medium. Here the situ-
ation is complicated by the intervention of an alternative nitration mechanism – that of nitrous
acid catalyzed nitration, which proceeds viain situnitrosation–oxidation (see Section 4.4).
Changing the composition of a nitrating agent like mixed acid, resulting in a change of
acidity, can have an effect on both regioselectivity and substrate reactivity.^75 The strongly
acidic nature of sulfuric acid in mixed acid mixtures is observed to perturb the nitration of
some substrates. This is most extreme in the case of some anilines, likeN,N-dimethylaniline,
where an excess amount of sulfuric acid results in amine protonation, deactivation of the
aromatic ring, and a complete reversal of selectivity fromo/p-tom-substitution.^76 Other
substrates are similarly deactivated by excess sulfuric acid. A striking example is seen with
benzoic acid which is nitrated approximately 20 times faster with mixed acid containing 95 %
sulfuric acid as compared to 100 % sulfuric acid.^77 A major factor in this reduction of activity