Compounds by nitration

An amino group may be introduced into an aromatic compound by nitration, followed by reduction25. Most aromatic compounds, whether of high or low reactivity, undergo nitration with one of a wide variety of nitrating agents26-28. The reduction of the nitro compounds to amines can also be effected by a variety of methods (equation 3). This... 

The nitrates and nitrites are best absorbed through the mucous membrane lining the mouth and nose. Therefore, they are usually administered sublingually or buccally. They may also be inhaled. When administered by these routes, the active ingredient is absorbed into the venous circulation and travels via the vena cava to the heart, aorta, and coronary arteries. If these agents are taken orally, they are metabolized to inactive compounds by nitrate reductase in the liver. 

Trinitrotri-p-lolylbismuthine dinitrate, (CH3.C6H3.N02)3 Bi(N03)a.—This IS prepared m a similar manner to the phenyl compound, by nitrating tri-p-tolylbismutlime dmitratc. The nitration requires two hours at room temperature. The product is a white crystalline powder, which, after crystallisation from acetone or ethyl acetate, explodes at about IG0° C. 

Manufacturers commonly produce nitrochlorobenzene compounds by nitrating chlorobenzene under acidic conditions. The reaction produces a mixture of isomers comprising by weight 34% ortho, 65% para, and 1% meta nitrochlorobenzenes. The isomers are separated by crystallization and distillation [25]. 

A mixture of the two mononitro-chlorobenzenes is prepared by nitration of chlorobenzene. Further nitration of the mixture or of either of the mononitro-compounds gives 2,4-dinitrochlorobenzene, m.p. 5 C, b.p. 315"C. 

We are not concerned here with the mechanism of nitrosation, but with the anticatalytic effect of nitrous acid upon nitration, and with the way in which this is superseded with very reactive compounds by an indirect mechanism for nitration. The term nitrous acid indicates all the species in a solution which, after dilution with water, can be estimated as nitrous acid. 

That some modification to the position so far described might be necessary was indicated by some experiments of Nesmeyanov and his co-workers. Amongst other compounds they nitrated phenyl trimethyl ammonium and triphenyloxonium tetrafluoroborates with mixed acid the former gave 96 % of m- and 4 % of -nitro compound (88 % total yield), whilst the latter gave 80% of the tri-(p-nitrophenyl)oxonium salt. Ridd and his co-workers have made a quantitative study of the phenyl trimethyl ammonium ion. Their results, and those of other recent workers on the nitration of several cations, are collected in table 9.3. 

The nitration of phenylpyridines and related compounds has attracted attention for a long time, and measurements of isomer proportions have been made for several compounds of this type. Nitration occurs in the phenyl ring. For 2-phenylpyridine and 2-phenylpyridine i-oxide measurements of the dependence of rate of nitration upon acidity in 75-81 % sulphuric acid at 25 °C show that both compounds are nitrated as their cations (table 8.1). The isomer distribution did not depend significantly upon the acidity, and by comparison with the kinetic data for quinolinium ( 10.4.2) the partial rate factors illustrated below were obtained.They should be compared with those for the nitration of 2-nitrobiphenyl ( 10.1). The protonated heterocyclic groups are much... 

Comparison of the behaviour of cinnoline 2-oxide (vi, i = O) with that of 2-methoxycinnolinium (vi, R = OMe) suggests that at high acidities the former is nitrated as its conjugate acid (vi, R = OH), but that as the acidity is lowered the free base becomes active. At high acidities 5- and 8-nitration are dominant, but as the acidity is lowered 6-nitration becomes increasingly important. The 5- and 8-nitro compounds are probably formed mainly or wholly by nitration of the conjugate acid, and the 6-nitro compound wholly or mainly from the free base. ... 

A two-step synthesis of indoles from o-nitrobenzaldehydes proceeds by condensation with nitromcthanc followed by reductive cyclization. Like the Leim-gruber Batcho method, the principal application of the reaction is to indoles with only carbocyclic substituents. The forniation of the o,p-dinitrostyrenes is usually done under classical Henry condensation conditions but KF/18-crown-6 in propanol was found to be an advantageous reaction medium for acetoxy-substituted compounds[1]. The o,p-dinitrostyrenes can also be obtained by nitration of p-nitrostyrenes[2]. 

The overall reactivity of the 4- and 5-positions compared to benzene has been determined by competitive methods, and the results agreed with kinetic constants established by nitration of the same thiazoles in sulfuric acid at very low concentrations (242). In fact, nitration of alkylthiazoles in a mixture of nitric and sulfuric acid at 100°C for 4 hr gives nitro compounds in preparative yield, though some alkylthiazoles are oxidized. Results of competitive nitrations are summarized in Table III-43 (241, 243). For 2-alkylthiazoles, reactivities were too low to be measured accurately. 

Nitrobenzotrichloride is also obtained in high yield with no significant hydrolysis when nitration with a mixture of nitric and sulfuric acids is carried out below 30°C (31). 2,4-Dihydroxybenzophenone [131 -56-6] is formed in 90% yield by the uncatalyzed reaction of benzotrichloride with resorcinol in hydroxyHc solvents (32) or in benzene containing methanol or ethanol (33). Benzophenone derivatives are formed from a variety of aromatic compounds by reaction with benzotrichloride in aqueous or alcohoHc hydrofluoric acid (34). 

OCjOC -Dinitroanthraquinones and Related Compounds. 1,5- and 1,8-Dinitroanthraquiaone are the key iatermediates for manufacturiag disperse blue dyes via dinitrodihydroxyanthraquiaoae and vat dyes via diaminoanthraquiaones. 1,5-Diaitroanthraquinone [82-35-9] (49) and 1,8-dinitroanthraquinone [129-39-5] (50) are prepared by nitration of anthraquiaone with nitric acid ia sulfuric acid. a,P -Dioitroanthraquiaoaes are also formed ia the reactioa. 

Methyl-1-nitroanthraquiaone [129-15-7] (57) is an important precursor for l-nitroanthraquiaone-2-carboxyhc acid (58) and is prepared by nitration of 2-methylanthraquiaone (56) (87). This compound is probably carciaogenic (88). 

Nitration of a series of methyl-1,2-benzisoxazoles was studied by Tahkar and Bhawal using fuming nitric acid and sulfuric acid in acetic acid at 100 °C. 3-Methyl-1,2-benzisoxazole gave a mixture of 5-nitro- and 5,7-dinitro-3-methyl-l,2-benzisoxazole, with the 5-nitro isomer predominant. The product obtained from 3,5-dimethyl-1,2-benzisoxazole was the 4-nitro derivative and not the 7-nitro compound as proposed by Lindemann (26LA(449)63). The synthesis of the 7-nitro compound by an alternative method was used as structural proof. Two products were obtained from 3,6-dimethyl-l,2-benzisoxazole and these were the 5-nitro and 5,7-dinitro derivatives. 3,7-Dimethyl-l,2-benzisoxazole was converted into the 5-nitro derivative (Scheme 25) (77lJC(B)l06l). 

Reduction of aryl nitro compounds (Section 22.9) The standard method for the preparation of an arylamine is by nitration of an aromatic ring, followed by reduction of the nitro group. Typical reducing agents include iron or tin in hydrochloric acid or catalytic hydrogenation. 

Finally, certain 3-substituted compounds can be prepared by utilizing the - meta) directing powet (cf. Section IV,B) of some groups in the 2-position which afterward can be removed. 3-Nitrothiophene is prepared by nitration of 2-thiophenesulfonyl chloride and by removal of the sulfonic acid group of the 4-nitro-2-sulfonyl chloride formed with superheated steam. Another approach to 3-nitrothio-phene is to nitrate 2-cyanothiophene, separate the 4-nitro-2-cyano-thiophene from the 5-isomer, hydrolyze, and decarboxylate. A final method of preparation of 3-nitrothiophene is by simultaneous de-bromination and decarboxylation of 5-bromo-4-nitro-2-thiophene-carboxylic acid obtained through the nitration of methyl 5-bromo-2-thiophenecarboxylate. 

Chloro- and 5-methylbenzofuroxans are readily nitrated in the 4-position the product rearranges easily to form 7-substituted 4-nitro compounds (see Section VIII), also obtained by nitration of the corresponding 4-substituted benzofuroxans. Dinitration of 5-methylbenzofuroxan is said to give a product of m.p. 133°, while the 4-methyl gives a dinitro compound m.p. 122°-123°. For other benzofuroxans to have been nitrated see refs. 19, 36, 81, 97,121. There appears to be some confusion over the site of electrophilic substitution of naphtho[l,2-c]furoxan. Early reports in the literature state that nitration gives the 5,6-dinitro derivative (47). However, sulfona-... 

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... 

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