4-Chloro-3-nitrobenzonitrile

Another synthesis of febuxostat (1) commenced with 4-chloro-3-nitrobenzonitrile 32. Attributed to the strong electron-withdrawing groups on the molecule, ether 33 was easily prepared from 32 and scc-butanol via treatment with NaH in DMF, although NaH/DMF is not a safe combination. The rest of the chemistry is quite similar to that reported previously, including the use of highly toxic KCN. 

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]. 

When chloro- and dichloroacetonitriles were reacted with o-aminocar-bonitrile 52, 4-chloro-2-chloromethyl- and 4-chloro-2-dichloromethyl-thieno[2,3-J]pyrimidines 53a and 53b were obtained, respectively. For compounds with stronger electron-withdrawing substituents on the C=N group, such as ethyl cyanoacetate, ethyl cyanoformate, 4-nitrobenzylcyanide, 4-nitrobenzonitrile, phenoxyacetonitrile, phenylthioacetonitrile, phenylsul-... 

C7H4CIF3N202 4-amino-3-chloro-5-nitrobenzotrifluoride 57729-79-0 25.00 1.5744 2 9829 C7H4N202 3-nitrobenzonitrile 619-24-9 25.00 1.3979 2... 

Chloro-6-nitrobenzonitrile, 519 5a-Chloro,6 -nitrocholestanyl acetate, 750 l-Chloro-4-(o-nitrophenyl>2-butene, 743 l-Chloro-2-nitroso-l,2-didesoxyglucose,751 iy -7-Chloronorcamphorquinone, 994 l-Chloro-3-pentanone, 388, 389 m-Chloroperbenzoic acid, 135-139,1192 p-Chlorophenol, 65 a-Chloro-a-phenylacetanilide, 1078... 

To study the substrate specificity of the hydroxylaminolyases, a set of substituted hydroxylaminoaromatic compounds was synthesized (Fig. 9). In initial experiments, the substrate-dependent oxygen uptake by 4-nitrobenzoate-grown cell suspensions was investigated (Table 2). The synthesized hydroxylaminoaromatic compounds and the corresponding nitroaromatic compounds were used as substrates. It is clear from Table 2 that 4-nitrobenzoate and 4-hydroxylaminobenzoate showed the highest oxygen uptake rate. However, 1-chloro-4-nitrobenzene, 4-nitrobenzonitrile, 4-nitroanisole and, to a... 

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