Nitrating agents, reactions

Nitric acid being the solvent, terms involving its concentration cannot enter the rate equation. This form of the rate equation is consistent with reaction via molecular nitric acid, or any species whose concentration throughout the reaction bears a constant ratio to the stoichiometric concentration of nitric acid. In the latter case the nitrating agent may account for any fraction of the total concentration of acid, provided that it is formed quickly relative to the speed of nitration. More detailed information about the mechanism was obtained from the effects of certain added species on the rate of reaction. 

Several electrophiles, such as acetic anhydride, nitric acid or alternative nitrating agents, such as ammonium nitrate in trifluoroacetic anhydride (41), or sodium hypochlorite, react at N-1, which is followed by reaction at N-3 under suitable conditions. In the case of acetic anhydride, the reaction can take place exclusively at N-3 if N-1 is hindered this fact has served as a criterion for studying the stereochemistry of 5-spirohydantoin derivatives (42,43). 

Nitration is defined in this article as the reaction between a nitration agent and an organic compound that results in one or more nitro (—NO2) groups becoming chemically bonded to an atom in this compound. Nitric acid is used as the nitrating agent to represent C-, 0-, and N-nitrations. O-nitrations result in esters. N-nitrations result in nitramines. 

Nitration of 4-(2-thienyl)- (301) and 4-(3-thienyl)-pyrazoles (302) mainly occurs on the thiophene ring, but when acetyl nitrate is used as the nitration agent small quantities of products nitrated on the pyrazole ring are isolated (position of the nitro group uncertain) (80CS( 15)102). Pyrazol-l -ylpyridines (303) undergo electrophilic reactions (bromination, chlorination and nitration) preferentially in the pyrazole ring. Thus, the nitration of (303 R = R = = H) either with a mixture of nitric acid and sulfuric acid at 10-15 °C or with... 

Nitration Hazards arise from the strong oxidizing nature of the nitrating agents used (e.g. mixture of nitric and sulphuric acids) and from the explosive characteristics of some end products Reactions and side reactions involving oxidation are highly exothermic and may occur rapidly Sensitive temperature control is essential to avoid run-away... 

Gariy nitration theories considered nitration as an addition reaction in which the initial step was the direct addition of the nitrating agent to the molecule undergoing nitration, eg ... 

As already mentioned (Section 1), the,prepn of most of the commonly used high expl compds involves one or more nitration reactions. Indeed, except for ammonium nitrate (AN), primary expls, and BkPdr, it is difficult to bring to mind any expl in common use (or even a laboratory curiosity) that was not prepared by nitration. In Table 1, we list the most important military and commercial high expl compds produced by nitration. We have grouped these compds by nitration type, ie C-nitration, O-nitration, and N-nitration. Note that either nitric acid or mixed acid are the nitrating agents principally employed in industry. This will be discussed further in the next section. The Table also gives Encyclopedia references for those compounds already described in previous Encyclopedia volumes... 

The most common indirect nitration method, often used in nitrating phenols, consists of sul-forating the compd and then replacing the sulfo group by a nitro group. The usual nitrating agent for these reactions is coned nitric acid... 

As already mentioned, Bunton and Halevi (Ref 38) found that ca 60% nitric acid requires the presence of nitrous acid for it to be a nitrating agent. Ingold et al (Ref 36c) postulated the action of nitrous acid to proceed via reactions 9, 10 11. Now in competition with reaction 11, there may be a nitrosation reaction ... 

Of course most of the above reaction sequences are possible if one starts with either N204 or N2Os as the nitrating agent... 

According to Kirk Othmer (Ref 34), the reactions of nitric acid may be classified conveniently into three groups (l) reactions as an acid (formation of inorganic nitrates) (2) reactions as an oxidizing agent and (3) organic reactions... 

Nitric acid also undergoes reactions with organic compounds wherein the acid serves neither as an oxidizing agent nor as a source of hydrogen ions. The formation of organic nitrates by esterification (O-nitration) involves reaction with the hydroxyl group ... 

The outstanding problem is to decide how much, if any, association exists between N02 and X" in the generally rate-determining step of the reaction. Kinetic studies tend to indicate the presence of different electrophiles under different conditions whereas the derived partial rate factors are closely similar and therefore indicate one electrophile common to most, if not all, nitrating agents. The more electron-attracting is X , the more easily is N02 displaced from it and hence a reactivity sequence should be... 

Most nitrations are highly exothermic and hence release a lot of reaction heat for most experimental protocols [37, 94]. This high exofhermidty may even lead to explosions [37, 38]. Nitration agents frequently display acid corrosion [37]. For these reasons, nitrations generally are regarded as being hazardous [37, 38]. 

Nitric acid and especially fuming acid is a strong oxidant and nitrating agent, especially when it is combined with sulphuric acid (formation of an electrophilic species). The dangers of the reactions which involve this compound are linked to the exothermicity of the reactions and the eventual formation, particularly in an aromatic series, of nitrated species that can be very unstable in some cases. 

This section is mainly concerned with reactions that involve nitric acid, of which behaviour is even more difficult to interpret. Indeed, nitric acid is not only a strong oxidant but also a nitrating agent,especially when it is combined with sulphuric acid. With nitrated derivatives it can also be destabilising due to its acidic property, which faciiitates the compounds decomposition. Since most reactions give rise to a detonation it is even more difficult to interpret the accidents. 

Nitroimidazoles substituted by an aromatic ring at the 2-position are also active as antitrichomonal agents. Reaction of p-fluorobenzonitrile (83) with saturated ethanolic hydrogen chloride affords imino-ether 84. Condensation of that intermediate with the dimethyl acetal from 2-aminoacetaldehyde gives the imidazole 85. Nitration of that heterocycle with nitric acid in acetic anhydride gives 86. Alkylation with ethylene chlorohydrin, presumably under neutral conditions, completes the synthesis of the anti-... 

Use of mixtures of metal nitrates with acetic anhydride as a nitrating agent may be hazardous, depending on the proportions of reactants and on the cation copper nitrate or sodium nitrate usually cause violent reactions [ 1], An improved procedure for the use of the anhydride-copper(II) nitration mixture [2] has been further modified [3] to improve safety aspects. 

---