Nitration reactions

Nitration of benzene is one of the most widely used reactions for benchmarking chemical reactors for liquid-liquid appUcation. This reaction is fast and highly exothermic (-145 kj mol ). In consequence, the reactor performance is strongly influenced by mass and heat transfer. The reaction is catalyzed by sulfuric acid that creates nitrating ions (NO ) from HNOg [69]. All reactions are assumed to take place within the acid phase. Poor mixing in this process reduces the transfer rates and leads to a buildup of dissolved nitrated products near the interface, which can be further nitrated to form often unwanted dinitro and trinitro compounds [84]. 

Nitration of toluene is another exothermic nitration performed in 150 pm bore PTFE tube for varying acid strengths, reactor temperatures, and flow ratios [84]. Here too a strong influence of flow velocity on transformation rates of toluene nitration was observed  

Results from both benzene and toluene nitration have indicated that reaction rate constants in the range of 0.5-20 min can be achieved in a capillary reactor 

---

Some of the nitration reactions we studied with N02 salts were the following. 

That numerous 2-amino-5-nitrothiazole derivatives exhibit antiamebic, antihistomonal, antitrichomonal, and antischistosomal properties (see Section VI.2) explains the large number of nitration reactions reported. Nitration in a mixture of concentrated nitric and concentrated sulfuric acids IS among the most common experimental methods (16, 27, 58, 374-377). 

This genera] scheme could be used to explain hydrogen exchange in the 5-position, providing a new alternative for the reaction (466). This leads us also to ask whether some reactions described as typically electrophilic cannot also be rationalized by a preliminary hydration of the C2=N bond. The nitration reaction of 2-dialkylaminothiazoles could occur, for example, on the enamine-like intermediate (229) (Scheme 141). This scheme would explain why alkyl groups on the exocyclic nitrogen may drastically change the reaction pathway (see Section rV.l.A). Kinetic studies and careful analysis of by-products would enable a check of this hypothesis. 

Fluorinated Acids. This class of compounds is characterized by the strength of the fluorocarbon acids, eg, CF COOH, approaching that of mineral acids. This property results from the strong inductive effect of fluorine and is markedly less when the fluorocarbon group is moved away from the carbonyl group. Generally, their reactions are similar to organic acids and they find apphcations, particularly trifluoroacetic acid [76-05-1] and its anhydride [407-25-0] as promotors in the preparation of esters and ketones and in nitration reactions. 

The overall nitration reaction between an aromatic and mixtures is as follows ... 

Because the highest possible interfacial area is desired for the heterogeneous reaction mixture, advances have also been made in the techniques used for mixing the two reaction phases. Several jet impingement reactors have been developed that are especially suited for nitration reactions (14). The process boosts reaction rates and yields. It also reduces the formation of by-products such as mono-, di-, and trinitrophenol by 50%. First Chemical (Pascagoula, Mississippi) uses this process at its plant. Another technique is to atomize the reactant layers by pressure injection through an orifice nozzle into a reaction chamber (15). The technique uses pressures of typically 0.21—0.93 MPa (30—135 psi) and consistendy produces droplets less than 1 p.m in size. The process is economical to build and operate, is safe, and leads to a substantially pure product. 

The iacreased chemical stabiUty of the 6-deoxytetracyclines allows chemical modification with retention of biological activity electrophilic substitutions have been carried out at C-7 and C-9 under strongly acidic conditions (46—53). Reactions of 6-deoxy-6-demethyltetracycline [808-26-4] (16), C21H22N2O7, with electrophiles, such as nitrate ion (49), bromomium ion (46,47) (from N-bromosuccinimide), or N-hydroxymethylphthalimide (53), yielded 7-substituted tetracyclines. In the case of the nitration reaction, both the 7- and 9-nitro isomers (17, X = NO2, Y = H) and (17, X = H, Y = NO2) were obtained. 

Dinitroanthraquinones are industrially prepared by nitration of anthraquiaone in mixed nitric—sulfuric acid at 0—50°C. The reaction mixture is then heated to a temperature slightly higher than the nitration reaction temperature to enrich the content of 1,5-dinitroanthraquinone in soHd phase, and then cooled and filtered to obtain the 1,5-dinitroanthraquinone wet cake. Mother Hquor is concentrated by distillation of nitric acid and crystallised 1,8-isomer is separated. The filtrate is again distilled, and precipitated ( -isomers are filtered off and filtrate is recycled to the nitration step (72—74). 

A study of the aromatic nitration reaction in aqueous nitric acid revealed that when no aromatic substrate was present, an incorporation of 0 from labeled water into nitric acid occurred. 

TWo types of rate expressions have been found to describe the kinetics of most aromatic nitration reactions. With relatively unreactive substrates, second-order kinetics, first-order in the nitrating reagent and first-order in the aromatic, are observed. This second-order relationship corresponds to rate-limiting attack of the electrophile on the aromatic reactant. With more reactive aromatics, this step can be faster than formation of the active electrq)hile. When formation of the active electrophile is the rate-determining step, the concentration of the aromatic reactant no longer appears in the observed rate expression. Under these conditions, different aromatic substrates undergo nitration at the same rate, corresponding to the rate of formation of the active electrophile. 

Such solutions are extensively used in aromatic nitration reactions in the heavy organic chemicals industry. See also pp. 457-8. 

Scheme 5.1-37 Aromatic nitration reactions in ionic liquids.

Similar to the alkylation and the chlorination of benzene, the nitration reaction is an electrophilic substitution of a benzene hydrogen (a proton) with a nitronium ion (NO ). The liquid-phase reaction occurs in presence of both concentrated nitric and sulfuric acids at approximately 50°C. Concentrated sulfuric acid has two functions it reacts with nitric acid to form the nitronium ion, and it absorbs the water formed during the reaction, which shifts the equilibrium to the formation of nitrobenzene ... 

Nitration of toluene is the only important reaction that involves the aromatic ring rather than the aliphatic methyl group. The nitration reaction occurs with an electrophilic substitution hy the nitronium ion. The reaction conditions are milder than those for henzene due to the activation of the ring hy the methyl substituent. A mixture of nitrotoluenes results. The two important monosubstituted nitrotoluenes are o- and p-nitrotoluenes ... 

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 second-stage nitration reaction is somewhat slower than first-stage nitration, but is nevertheless quite rapid in comparison to prior art methods, being substantially complete within a matter of from about two to six minutes under the preferred conditions of the invention, and seldom, if ever, requiring longer than about 12 to 15 minutes ... 

Hercules states that the change from batch to continuous nitration involves no change in raw materials, and no change in the nitration reaction. The product of the continuous process is identical with that of the older batch process, except that it is more uniform... 

Since mixing of glycol and MA was very thorough and rapid this AT mirrors the progress of the exothermic nitration reaction. Note the strong influence of mixed acid water content on the nitration rate. This agrees with Oehman et al (Ref 56a), except that Roth et al observed... 

The product obtained from this distillation usually contains small amounts of acetone cyanohydrin acetate, as evidenced by an ester carbonyl band at 1740 cm.-1 in its infrared spectrum. This material does not interfere with the nitration reactions of the reagent. It may be removed by fractionation through a more efficient column. 

The aqueous solution contains a-morpholinoisobutyronitrile in the form of its hydrochloride. It is formed by condensation of morpholine with the acetone and hydrogen cyanide formed in the nitration reaction. It is because of this side reaction that the excess amine is employed. 

The presence of PSCs also leads to the removal of nitrogen oxides (NO and NO2) from the gas phase. As long as there are significant amounts of NO2 it will react with chlorine monoxide (CIO) to produce chlorine nitrate (reaction 11). This species subsequently reacts with HQ on PSC surfaces to produce nitric acid (reaction 13), which remains in the condensed phase. Also, nitric acid directly condenses with water to form nitric acid trihydrate particles, hence it is not available to regenerate NO2 by photochemical processes, as it does when it is in the gas phase. 

Replacement of a hydrogen of benzene by chlorine is termed chlorination. When one or more hydrogens are replaced by an -NO2 (nitro group), it is called nitration. Reaction of benzene with sulfuric acid, a reaction known as sulfonation, leads to a sulfonic acid. Note that in each substitution reaction, a small hydrogen-containing compound is formed. 

Corning Hazardous nitration reaction in collaboration with DSM at 800-tons-per-year capacity [7]... 

Aromatic Nitration Reactions Investigated in Micro Reactors... 

---