3-Nitro-7-azaindole

Nitro-7-azaindole was obtained in 83% yield at 0°, and was reduced to the 3-amino compound, which is unstable as the free base,... 

Recent work on the thermal indolization of arylhydrazones has introduced new synthetic possibilities for azaindoles. Kelly et al. refluxed cyclohexanone and deoxybenzoin 2-pyridylhydrazones in diethylene glycol to give 5,6,7,8-tetrahydro-a-carboline (42, R = H) and 2,3-diphenyl-7-azaindole in 70 and 56% yields, respectively, compared with 53 and 12% reported earlier. Similarly, y-carboline 29 was obtained in 95 % yield from cyclohexanone 4-pyTidylhydrazone (lit. 48% ). Several 7-azaindole derivatives were prepared in the same manner. The yields ranged from 5 % for azaindolenine (31) to 88% for 3-phenyl-7-azaindole. 3,3-Dimethyl-7-azaindolenine was obtained in 47 % yield from the isobutyralaldehyde hydrazone. The novel cyclic compounds 40 and 41 were obtained from the 2-pyridylhydrazones of cyclopentanone, a-indanone, and a-tetralone in 67, 95, and 77% yields, respectively. Unfortunately, all attempts to cyclize the acetone, pyruvic acid, and ethyl pyruvate hydrazones were unsuccessful. Also, cyclohexanone and methyl ethyl ketone 5-nitro-2-... 

The Reissert synthesis of indoles has found much success with o-nitrotoluenes, but has been tried for the s5nithesis of azaindoles in only a few cases. Herz and Murty first reported unsuccessful attempts at base-catalyzed condensation of ethyl oxalate with 4-nitro-3-picoline and its Y-oxide (45). No conditions were reported. Later,... 

All efforts to prepare 4- and 6-azaindole by the reductive cyclization of 3-nitro-2- and 3-riitro-4-p5T idylcyanoacetates were unsuccessful. ... 

Azaindoles are nitrated readily by treatment with fuming nitric acid at 0°. In his early work, Fischer nitrated apoharmine, obtaining a high-melting crystalline compound, which reacted with methyl iodide and alkali, to give, presumedly, 3-nitro-6,7-dimethyl-6fl -6-azaindole. The stepwise decarboxylation of harminic acid gives a monocarboxylic acid, 7-methyl-6-azaindole-2-carboxylic acid, which was also nitrated. The position of nitration was not established in either case. 

Good evidence for nitration at the 3-position was provided by Clayton and Kenyon. l-Benzoyl-2,5-dimethyl-4-azaindole was nitrated in 60 % yield, and followed with potassium permanganate oxidation in aqueous acetone gave 3-benzamido-6-methylpicolinic acid. Alkaline hydrolysis of the nitration product gave 3-nitro-2,5-dimethyl-4-azaindole (85% yield), which was also obtained by direct nitration of 2,5-dimethyl-4-azaindole in low yield. In addition, reduction gave the 3-amino compound, which was identical to that obtained by catalytic reduction of the product formed by coupling the azaindole with benzenediazonium chloride. 

The series of unsubstituted, 6-chloro-, and 6-methoxy-4-methyl-7-azaindoles were nitrated at —10° to give the corresponding 3-nitro compounds in 56,57, and 60 %yield, respectively. At 0°, the methoxy isomer gave what appeared to be the 1,3-dinitro compound, which decomposed explosively on heating. 

The iV -phenyl derivatives show blue shifts with bana separation indicating a greater energy required for electron delocalization in the azaindole ring system. The strong long-wavelength band for the p-nitro compound is characteristic of substituted nitrobenzenes. 

Draw structures for the azaindoles resulting from treatment of 2-methyl-3-nitro-and 4-methyl-3-nitropyridines, respectively, with (Et02C)2/Et0Na, followed by H2/Pd-C. Both products have the molecular formula C10H10N2O2. 

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