Nitrobenzonitril

Nucleophilic aromatic substitutions involving loss of hydrogen are known. The reaction usually occurs with oxidation of the intermediate either intramoleculady or by an added oxidizing agent such as air or iodine. A noteworthy example is the formation of 6-methoxy-2-nitrobenzonitrile from reaction of 1,3-dinitrobenzene with a methanol solution of potassium cyanide. In this reaction it appears that the nitro compound itself functions as the oxidizing agent (10). 

The synthesis of benzo[6]thiophenes from o-nitrobenzaldehydes or o-nitrobenzonitriles and methyl thioglycollate can be viewed as an extension of the foregoing approach (Scheme 64) (72JOC3224). 

Controlled hydrogenation over Ni or the electrochemical reduction of o -nitrobenzo itriles produced 3-amino-2,l-benzisoxazoles either as the major product or by-product, depending in part on the reaction media and ratio of reactants (72BSF2365, 65CB1562). Reduction of o-nitrobenzonitrile gave either 3-amino-2,l-benzisoxazole or 2-aminobenzonitrile. The benzisoxazole is presumed to arise via an intermediate hydroxylamine. The electrochemical reduction of o-nitrobenzonitrile at acid pH produced the hydroxylamine as the primary product. Reduction at neutral pH gave the amino-2,1-benzisoxazole and the hydroxylamine (72BSF2365). 

Reductions of nitronitriles situated to favor interaction are apt to involve both functions (S4,93). Hydrogenation of o-nitrobenzonitrile over either palladium or platinum gave o-aminobenzamide (78), with the amide oxygen transferred from the nitro group (66). On the other hand, l-amino-2-cyanonaphthalene gave the amino amide on reduction over Pt02, but the amino nitrile over palladium (82). 

The chemistry of indium metal is the subject of current investigation, especially since the reactions induced by it can be performed in aqueous solution.15 The selective reductions of ethyl 4-nitrobenzoate (entry 1), 2-nitrobenzyl alcohol (entry 2), l-bromo-4-nitrobenzene (entry 3), 4-nitrocinnamyl alcohol (entry 4), 4-nitrobenzonitrile (entry 5), 4-nitrobenzamide (entry 6), 4-nitroanisole (entry 7), and 2-nitrofluorenone (entry 8) with indium metal in the presence of ammonium chloride using aqueous ethanol were performed and the corresponding amines were produced in good yield. These results indicate a useful selectivity in the reduction procedure. For example, ester, nitrile, bromo, amide, benzylic ketone, benzylic alcohol, aromatic ether, and unsaturated bonds remained unaffected during this transformation. Many of the previous methods produce a mixture of compounds. Other metals like zinc, tin, and iron usually require acid-catalysts for the activation process, with resultant problems of waste disposal. 

When the published method [1] for preparing the 4-isomer is used to prepare 2-nitrobenzonitrile, a moderate explosion often occurs towards the end of the reaction period. (This may be owing to formation of nitrogen trichloride as a byproduct.) Using an alternative procedure, involving heating 2-chloronitrobenzene with copper(I) cyanide in pyridine for 7 h at 160°C, explosions occurred towards the end of the heating period in about 20% of the preparations [2],... 

Besson and coworkers reported an original approach for the synthesis of the rare thiazolo-[5,4-/]-quinazoline 29 in six steps [15] from commercially available 2-amino-5-nitrobenzonitrile 22 (Scheme 8.11). The authors studied the transposition of four steps (ii, iii, vi, and vii) of the synthesis of thiazoloquinazoline 29 to microwave irradiation of solutions, with the same concentration of starting material and volume of solvent, and found that yields of the desired compounds were better than those obtained by conventional heating (Tab. 8.3). The overall time for the synthesis of 29 was considerably reduced and the overall yield was enhanced. 

A similar approach, synthesis of a selectively substituted benzotriazole from the corresponding ortfe-nitroaniline, is depicted in Scheme 212. The process starts from a microwave-assisted substitution of the fluorine atom in 4-fluoro-3-nitrobenzonitrile 1270 by isopropylamine to give ortfo-nitroaniline 1271 in 99% yield. Reduction of the nitro group provides ortfo-phenylenediamine 1272 that is directly converted to 5-cyano-l-isopropylbenzotriazole 1273, which is isolated in 83% yield <2006JME1227>. 

The 3,4-bis(4-fluorophenyl)-l,2,5-oxadiazole 2-oxide 324 was found as a side product in the synthesis of isoxazole derivatives (Scheme 82, method A) <2006AXEo4827>. Dimerization of 3- and 4-nitrobenzonitrile A-oxides gave corresponding 1,2,5-oxadiazole A-oxides (Scheme 82, method B) <1999MI111>. 

A phosphorylnitrile oxide (Me2CH0)2P(0)CN0 reacts with tetracyanoethy-lene to give the bisadduct 330 (296). Reaction of cyanodinitrochloromethane with 3-nitrobenzonitrile oxide gives 5-chlorodinitromethyl-3-(3-nitrophenyl)-l,2,4-oxadiazole 331 (394). 

The reaction of 3-nitrobenzonitrile (R2 = 3-N02Ph) and dimethyl malo-nate in the presence of SnCl4 in boiling 1,2-dichloroethane for 1 hr gave dimethyl amino(3-nitrophenyl)methylenemalonate (312, R = R1 = Me R2 = 3-N02Ph, R1 = 3-N02C6H4) in 66% yield (87EUP228845). 

Aromatic nitriles differ from their aliphatic cousins in that they bear no H-atoms at C(a) and, hence, cannot undergo oxidative denitrilation. Here, hydrolysis of the CN group depends on the substrate properties and on the relative efficiency of competitive reactions such as ring hydroxylation. Thus, the CN group of benzonitrile (11.87, R = H), 2- and 4-hydroxybenzonitriles (11.87, R = 2-OH or 4-OH), and 4-nitrobenzonitrile (11.87, R = 4-N02) was not hydrolyzed by rat liver subcellular preparations [124],... 

Fig. 3 Electrochemical and homogeneous standard free energies of activation for self-exchange in the reduction of aromatic hydrocarbons in iV.A -dimethylformamide as a function of their equivalent hard sphere radius, a. 1, Benzonitrile 2, 4-cyanopyridine 3, o-toluonitrile 4, w-toluonitrile 5, p-toluonitrile 6, phthalonitrile 7, terephthalonitrile 8, nitrobenzene 9, w-dinitrobenzene 10, p-dinitrobenzene 11, w-nitrobenzonitrile 12, dibenzofuran 13, dibenzothiophene 14, p-naphthoquinone 15, anthracene 16, perylene 17, naphthalene 18, tra 5-stilbene. Solid lines denote theoretical predictions. (Adapted from Kojima and Bard, 1975.)...

The photoreduction of eight electron-acceptor- and four electron-donor-substituted nitrobenzenes has been studied and quantum yields for either starting material disappearance or product formation have been reported 7). Photolysis of 4-nitrobenzonitrile and 4-nitrotoluene in air-saturated solutions was completely quenched and thus a triplet multiplicity of the reacting excited state was derived 7). 

In nitriles containing a nitro group the latter is reduced preferentially by iron and by stannous chloride. 2-Chloro-6-nitrobenzonitrile was reduced to 2-chloro-6-aminobenzonitrile with iron in methanol and hydrochloric acid in 89% yield [7769], and o-nitrobenzonitrile to o-aminobenzonitrile with stannous chloride and hydrochloric acid in 80% yield [779]. 

The formation of nitriles from aldoximes was at that time a well-known reaction, at least in its general lines. Gabriel and Meyer found that o-nitrobenzonitrile was obtained by heating o-nitrobenzaldoxime, prepared in an indirect way, with sodium acetate and acetic anhydride Lach prepared benzonitrile in a similar way, and Dollfuss transformed aldoximes of the aliphatic series into nitriles by simple treatment with acetic anhydride. The complicated character of this reaction was demonstrated by the classical work of Beckmann and Hantzsch, who... 

---