O-Nitrobenzonitrile

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). 

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... 

A variety of substituted 3-aminobenzo[6]thiophenes have been obtained by ring closure reactions of nitriles (equation 57). Various o -cyanophenylthioacetyl derivatives, when treated with base, yield the 3-amino derivatives (Section 3.15.2.2.3). The benzonitriles may be obtained by displacement of the o-nitro group from o -nitrobenzonitriles (74JOC3440). 2-Arylthio-l-chloroenamines are cyclized to 3 -dialkylaminobenzo[6]thiophenes in the presence of Lewis acid catalysts (equation 58). The 1 -chloroenamines may be prepared from t-amides or ynamines <8lH(15)l 179>. 

In the nitrobenzonitriles, such resonant structures will be mutually suppressed and consequently no large deviations from the additivity rule occur, such as exist when the two groups are of opposite charge so that the resonance is augmented by additional valence bond structures. The dipole moment of />-nitrobenzonitrile is zero, of o-nitrobenzonitrile, 6 19, D and m-nitro-benzonitrile, 3-78, D. Similar behaviour is observed with the di-substituted halogen derivatives of benzene and with the phenylenediamines. 

The submitter states that a number of aromatic mono-and dinitriles have been prepared by this procedure vvith slight or no modification in the temperature. The reaction mixtures were usually worked up by the acetone-ammonia method described in Note 6. Among the compounds prepared by this method are o-nitrobenzonitrile, o-bromobenzonitrile, w-methoxy-benzonitrile, 4,4 -dicyanodiphenylsulfone, 4,4 -dicyanostilbene, a,7-di-(4-cyanophenoxy)propane. With the last, a temperature of 185 190° for 20 minutes gave the best results. The yields before purification ranged between 75% and 95% and after purification between 63% and 79%. Aliphatic acids give low yields of the corresponding nitriles and, in some cases, chlorinated by-products. 

Reductive cyclization of polychloro-o-nitrobenzaldehydes and nona-fluoro-o-nitrobenzophenone with tin and acetic acid and stannous chloride and hydrochloric acid, respectively, proceed without hydrodehalogena-tion.137,138 3-Aminoanthranil is obtained, albeit in low yield (17%), by electrolytic reduction of o-nitrobenzonitrile.139... 

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