Nitration conditions

Conflicting reports on the nitration of phenazine have appeared, but the situation was clarified by Albert and Duewell (47MI21400). The early work suggested that 1,3-dinitroph-enazine could be prepared in 66% yield under standard nitration conditions however, this proved to be a mixture of 1-nitrophenazine and 1,9-dinitrophenazine (24). As with pyrazines and quinoxalines, activating substituents in the benzenoid rings confer reactivity which is in accord with valence bond predictions thus, nitration of 2-methoxy- or 2-hydroxy-phenazine results in substitution at the 1-position. 

Pyrazole is very stable in acid media and even under more vigorous nitration conditions neither ring opening nor ring oxidation was observed (for oxidation to pyrazolones with a mixture of bromine and nitric acid see Section 4.04.2.1.4(v)). 

Nitration of 2-amino-l,8-naphthyridin-5(8H)-one (67a) in acetic acid or in acetic anhydride does not occur in HNO3/H2SO4 the products obtained were difficult to separate (72GCI253). Hydrolysis of the amino group under nitration conditions has also been observed with 6- and 7-carboxy-2-aminonaphthyridin-5(8H)-ones (67b/67c), yielding the corresponding (68b/ 68c) (72GCI253). 

Nitration can be catalyzed by lanthanide salts. For example, the nitration of benzene, toluene, and naphthalene by aqueous nitric acid proceeds in good yield in the presence of Yb(03SCF3)3.5 The catalysis presumably results from an oxyphilic interaction of nitrate ion with the cation, which generates or transfers the N02+ ion.6 This catalytic procedure uses a stoichiometric amount of nitric acid and avoids the excess strong acidity associated with conventional nitration conditions. 

Figure 8. TG, OTG curves and rate of ammonia evolution (arbitrary units) for melamine nitrate. Conditions as Figure 2.

Topchiev has given an extensive discussion of nitrating conditions used, and the products obtained, for all manner of aromatic substrates. 

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. 

Depending on the amine substrate and the nitrating conditions used, it is not uncommon for an intermediate nitramine to undergo direct rearrangement to the ring-nitrated product without prior isolation, in which case, the formation of the nitramine as an intermediate can only be postulated. Due to the high o-selectivity often observed with this type of reaction the o/p-ratio can be very different to that where the aromatic ring is directly nitrated. 

Under more vigorous nitration conditions the products from quinoline are 5,7- and 6,8-dinitroquinoline. Nitration of 6-nitroquinoline with potassium nitrate and sulfuric acid in a sealed tube at 140°C gives 5,6- and 6,8-dinitroquinoline under the same conditions 7-nitroquinoline gives 5,7- and 7,8-dinitroquinoline. 

The cyclodextrins can be nitrated using conventional techniques that are used for the preparation of NC where the degree of nitration is controlled by varying the nitration conditions. The energetic organic nitrate esters used for plasticization of cyclodextrin nitrates include 1,1,1-trimethylole thane trinitrate (TMETN),... 

Recently, Bogdal and D. Smolenski [18] made an extensive investigation of the conditions of formation of m-nitrotetryl. Contrary to the previous work of Romburgh [15] they found that m-nitrotetryl was formed in larger quantity when dimethylaniline was nitrated. Methylaniline yielded a smaller amount of m-nitrotetryl under identical nitration conditions. 

In practice the nitrating conditions most frequently applied are those which permit the composition of the spent acids after nitration to approximate to the mixture M3. 

The reaction of the diamino compound (107) under several different nitration conditions led to the formation of 5-nitroamino-8-aminopyrazino[2,3-d]pyridazine exclusively (68JHC53). 5,8-Dimorpholino substituted pyrazino[2,3-d]pyridazines are known to react with Grignard reagents to give 3-substituted 3,4-dihydro derivatives (75CPB1488). The dimorpholino heterocycles are also known to react photochemically with alcohols and cyclic ethers in the presence of photosensitizers to give 3-substituted 3,4-dihydro derivatives (Scheme 3) (75CPB1500). 

The nitration of l,5-naphthyridin-2- and -4-one gave, in both cases, the 3-nitro derivative.64 The 2-oxo-3-nitro- and the 5-oxo-8-nitro-l,6-naphthyridines were obtained by Albert and Armarego58 from the corresponding parent oxo compounds under nitrating conditions. 

Nitration of the sulfonation product of benzo[6]thiophene, followed by desulfonation of the resulting products, gives a mixture of nitro-benzo[6]thiophenes, the composition of which depends on the nitration conditions (Section VI, E, l).84... 

The Natl Fire Protection Assoc (Ref 10) reports the following expl reactions of toluene with nitric-sulfuric acids (if nitration conditions are not properly controlled) (p 272 of 491M) and with nitrogen tetroxide (p 278 of 491M). Also reported is the shock-sensitive solvated salt formed with silver perchlorate-acetic acid (pp 367-68 of 491M)... 

This mechanism seems to imply that if some substitution occurs at the classical position of attack (the first a complex), then such a substitution should show the deuterium isotope effect for proton loss from this position. The deuterium effect is absent in the majority of nitration cases, except for nitration in sterically shielded positions (Schoffield 1980). Perhaps a systematic investigation of kinetic isotopic effects would be useful in a much wider range of substrates in comparison with their ionization potentials and nitration conditions. 

Evidence for the influence of protonation was convincingly adduced from the trend of the quantity m p (mixed acid)lm p (acetyl nitrate) in the series Ph.CH2.OMe, Ph.(CH2)2.OMe, Ph.(CH2)3.OMe, but it was argued that protonation in mixed acid cannot explain the change in o />-ratios with change of nitrating conditions. Thus, it was supposed... 

Otherwise, the 1,2,3,4-thiatriazole ring is chemically rather inert, for example, surviving treatment with alcoholic base, under chlorination, and nitration conditions. An exception is the reduction of 5-phenyl-l,2,3,4-thiatriazole 41 with LiAlH4 to give benzylthiol 42 (Equation 4) <1964AHC263>. 

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