Reductive cyclization of aromatic nitro

Reductive cyclization of aromatic nitro compounds with triethyl phosphite, 48,115... 

Azole approach. Application of the commonly used method for reductive cyclization of aromatic nitro compounds by means of triethyl phosphite to the 4-c-nitrobenzylidene oxazoles (249) leads to the fused quinolines (250) (69JCS(C)385). 

This reaction can be traced back to the initial work of Cadogan for the preparation of car-bazole by the reductive cyclization of aromatic nitro compounds with triethyl phosphite. This reaction was then extended by Sundberg to the fornnation of indoles by the treatment of o-nitrostyrene with triethyl phosphite or the formation of indolines from the o-alkyl nitrobenzenes. Thus the formation of indole from the reduction of o-nitfostyrenes is referred to as the Cadogan-Sundberg indole synthesis." ... 

Perhaps the most reliable method for the reductive cyclization of a nitro ester to a hydroxamic acid is that which involves treatment with sodium horohydride in the presence of palladium on charcoal. Although under these conditions aromatic nitro compounds are reduced to amines, o-nitro esters such as 53, in which the ester group is suitably oriented with respect to the nitro group, give good yields of cyclic hydroxamic acids (54). Coutts and his co-... 

Similar to the Fisher indole synthesis, reductive cyclization of nitro aromatics offers a powerful means of forming indoles. Reductive cyclization of ortho, 2 -dinitrostyrenes has occurred in many ways, by TiCl3, NaBH4-Pd/C, H2-Pcl/C, and other reductive methods.89 Corey and coworkers have used the Borchardt modification (Fe-AcOFI, sihca gel, toluene at reflux for the reductive cyclization of o-ji-dinitrostyrenes) to prepare 6,7-dimethoxyindole (Eq. 10.65) in a total synthesis of aspidophytine (see Schemes 3.3 and 3.4 in Section 3.2.l).89d... 

The reduction of aromatic nitro compounds to amino derivatives and cyclizations to various heterocyclic compounds are presented in Chapter 9. Recent advances are presented here. Reaction of 2-nitrobenzaldehyde with vinyl carbonyl compounds in the presence of 1,4-diazbi-cyclo[2.2.2]octane affords Baylis-Hillman products, the catalytic reduction of which results in direct cyclization to quinoline derivatives (Eq. 10.78).134... 

Another important synthesis involves the reductive cyclization of 4-ethoxyalkylidinehydrazino-5-nitropyrimidines of type (372), which are obtained readily by reaction of 4-hydrazino-5-nitro-pyrimidines (371) with ortho esters. Catalytic reduction of the nitro group in (372) affords the 5-aminopyrimidine intermediate (373), which cyclizes in situ to the dihydro product (374). This may be oxidized without isolation to give the fully aromatic product (375). These reactions are shown in... 

Reduction of T [l-(2-nitrophenyl)-l//-pyrrol-2-yl]sulfonyl -acetone or -1-phenylethan-l-one with sodium borohy-dride and 5% palladium on carbon, a reagent known to convert aromatic nitro compounds to hydroxylamines, triggers intramolecular interaction and gives pyrrolo[l,2- ][3,l,6]benzothiadiazocine derivatives 90 (Equation 11 <2001MI1405, 2004T8807>). This method was further successfully applied to the reductive cyclization of 2- [l-(2-nitrophenyl)-17/-pyrrol-2-yl]sulfanyl acetonitrile. 

In a similar vein, the amino group in sulfide 14 (obtained presumably by an aromatic displacement reaction) is first converted to the bromide by Sandmeyer reaction to give 25. Reduction of the nitro group (16) followed by cyclization gives the substituted phenothiazine. Alkylation with the familiar halide (3) affords dimethothiazine (18). ... 

Since most anilines are derived from nitro intermediates the reduction of the aromatic nitro group followed by cyclization of the aniline in situ has offered a direct approach to the synthesis of quinolines. The ort/io-nitro cinnamic acid derivatives 28 undergo cyclization, where R corresponds to R , respectively, when treated with zinc in near-critical water at 250 °C... 

Gronowitz found the Pictet-Spengler reaction a convenient route for the preparation of (259 equation 22) (70AK(32)217). Thiophene-3-carbaldehyde was condensed with nitromethane to give w-nitrovinylthiophene. Reduction of the nitro derivative with LAH afforded the /3-(thienyl)ethylamine. The condensation of this amine with formaldehyde to the corresponding imine followed by cyclization with hydrochloric acid proceeded very smoothly and in high yield. The aromatization was achieved with potassium ferricyanide in an alkaline dioxane-water mixture. 

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