Side-reactions, aromatic nitration

Manufacture and Processing. Mononitrotoluenes are produced by the nitration of toluene in a manner similar to that described for nitrobenzene. The presence of the methyl group on the aromatic ring faciUtates the nitration of toluene, as compared to that of benzene, and increases the ease of oxidation which results in undesirable by-products. Thus the nitration of toluene generally is carried out at lower temperatures than the nitration of benzene to minimize oxidative side reactions. Because toluene nitrates at a faster rate than benzene, the milder conditions also reduce the formation of dinitrotoluenes. Toluene is less soluble than benzene in the acid phase, thus vigorous agitation of the reaction mixture is necessary to maximize the interfacial area of the two phases and the mass transfer of the reactants. The rate of a typical industrial nitration can be modeled in terms of a fast reaction taking place in a zone in the aqueous phase adjacent to the interface where the reaction is diffusion controlled. 

Multi-phase processing of nitrated aromatics is also described in [31], including both organic and aqueous phases. Side reaction take place in the organic phase, whereas all other reactions occur in the aqueous phase and are limited by organic solubility. For this reason, enabling mass transfer by large interfaces is a key to affect product selectivity. 

A novel, mild system for the direct nitration of calixarenes has been developed using potassium nitrate and aluminum chloride at low temperature. The side products of decomposition formed under conventional conditions are not observed in this system, and the p-nitro-calixarenes are isolated in 75-89% yields.17 Such Friedel-Crafts-type nitration using nitryl chloride and aluminum chloride affords a convenient system for aromatic nitration.18 Nitryl chloride was previously prepared either by the oxidation of nitrosyl chloride or by the reaction of chlorosulfonic acid with nitric acid. However, these procedures are inconvenient and dangerous. Recently, a mixture of sodium nitrate and trimethysilyl chloride (TMSC1) has been developed as a convenient method for the in situ generation of nitryl chloride (Eq. 2.6). 

Nitryl halides effect the nitration of aromatic substrates in the presence of Lewis acids, although competing halogenation is a side-reaction in some cases."" ... 

H. Suzuki, Side Reactions in Aromatic Nitration, Synthesis 1977, 217-238. 

For monographs, see Olah Malhotra, Narang Nitration Methods and Mechanisms-, VCH New York, 1989 Schofield Aromatic Nitration Cambridge University Press Cambridge, 1980 Hoggett Moodie Penton Schofield. Ref. 30. For reviews, see Weaver, in Feuer Chemistry of the Nitro and Nitroso Groups, pt. 2 Wiley New York. 1970. pp. 1-48 de la Mare Ridd, Ref. 59, pp. 48-93. See also Ref. 1. For a review of side reactions, see Suzuki Synthesis 1977, 217-238. 

Accident statistics formerly showed nitration as the most widespread and powerfully destructive industrial unit process operation (it has been overtaken by polymerisation). This is because nitric acid can, under certain conditions, effect complete and highly exothermal conversion of organic molecules to gases, the reactions often being capable of acceleration to deflagration or detonation. Case histories are described and safety aspects of continuous nitration processes are discussed in detail [1]. Of the 25 chapters of the book [2], each a paper presented at the symposium on Advances in Industrial and Laboratory Nitrations at Philadelphia in 1975, 3 deal with safety aspects of nitration Ch. 8, Hanson, C. etal., Side Reactions during Aromatic Nitration, Ch. 22, Biasutti, G. S.,... 

The use of iodine-containing pseudohalogens has been demonstrated to cause a variety of side reactions. Treatment of methyl 5-0-benzoyl-2,3-dideoxy-3-D-g/ycero-pent-2-enofuranoside (83, Scheme 22) with nitryl iodide afforded none of the desired addition product, but gave a quantitative yield of furfuryl benzoate (86). The same result was obtained by treating 83 with iodine nitrate, or with iodine alone.125 The rationale for this undesired result lies in the ability of iodine to act as a Lewis acid, polarizing the glycosidic bond, generating an oxacarbenium cation, which then decomposes to the stable aromatic 86. 

For side reactions in aromatic nitration see H. Suzuki, Synthesis, 1977, 217. 

Uses. Tetramethylene sulfone has high solvent power for aromatics and has been used extensively by Olah and co-workers for Friedel-Crafts type nitrations and for studies of the mechanism of nitronium tetrafluoroborate nitration of alkyl-benzenes and halobenzenes in homogeneous solution. It is a superior solvent for quaternization of tertiary amines with alkyl halides, since it has a high dielectric constant and does not enter into side reactions observed with nitrobenzene and dimethylformamide. For example in the synthesis of the acridizinium salt (3), Bradsher and Parham effected quaternization of (1) with benzyl bromide in tetramethylene sulfone at room temperature in excellent yield. Several other salts analagous to (2) were obtained in good yield and in crystalline form with use of tetramethylene sulfone, whereas with other solvents the products were colored... 

Side reactions that occur in this process with diazonium halides and nitrates prevent the diazotization being effected in nitric or hydrochloric acid solution it is necessary to do this in sulfuric acid solution, and the sparing solubility of the sulfates of aromatic amines necessitates certain departures from the usual diazotization procedures. 

Aromatic amines, like phenols, are very easily nitrated. However, primary and secondary amines in particular readily undergo oxidative side reactions, so that it is advisable to protect the amino group by acylation or by conversion by an aldehyde into the Schiff base. Even using a large excess of sulfuric acid protects the amino group to a considerable extent, owing to formation of the ammonium salt, but then entry of the nitro group is directed to a considerable extent into the meta-position. The usual A-acyl derivative is the acetyl compound, but benzoyl, /7-toluenesulfonyl, oxalyl, ethoxycarbonyl (from chloro-formic ester), and phthaloyl derivatives are also used. 

Aromatic nitration has been studied in great detail for several decades, and as a result, it stands as one of the relatively few well understood phenomena in organic chemistry. However, the oxidation processes that accompany nitration in most cases are little understood. In particular, in cases of the nitration of severely deactivated aromatic compounds, where conditions of strong acid and high temperatures must be employed, Q) the oxidation of substrate can be a significant, undesirable side reaction. At worst, in the case of 3,5-dinitrotoluene, for example, oxidation is the reported sole mode of reaction (2). 

HANSON ET AL. Side Reactions During Aromatic Nitration... 

The most coiiprehensive contribution to knowledge of side reactions during aromatic nitration up to the present time heis been made by Dadak and co-workers in a series of four papers(10-13). During toluene nitration, they detected the formation of nitrocresols, p-nitrophenol, 4,6 dinitrocresol, 2,4 dinitrophenol and 3 nitro-4 hydroxy-benzoic acid. They reported some quantitative analyses for this and other nitrations, although they did not Investigate a wide range of reaction conditions. 

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