3-nitroindoles

The values of the 1-hydroxy moiety of (5)-(- -)-iVb-acetyl- 1-hydroxytrypto-phan methyl ester (32), methyl l-hydroxyindole-3-butylate (33), iVb-methoxy-carbonyl-l-hydroxytryptamine (34), 1-hydroxymelatonm (19), l-hydroxy-6-nitroindole (35), and l-hydroxy-5-nitroindole (36) are determined to be 9.8, 8.4, 8.2, 8.1, 6.9, and 6.8, respectively (Fig. 2) (2000H1881). Thus, 1-hydroxyindoles are weak acids, stronger than phenol and weaker than succinimide. Therefore,... 

The effect of a nitro group at the 6 position on the nucleophilic substitution reaction has been examined using l-methoxy-6-nitroindole (82) as a substrate (2001H1151). The reaction with NaOMe in refluxing DMF generates 6-nitroin-dole (83, 57%), 2-methoxy- (199, 22%), and 3-methoxy-6-nitroindoles (84, 6%) (Scheme 29). The formation of 199 and 84 can be explained by the SN2 -type nucleophilic substitution reaction at the 2 and 3 positions, respectively, with the... 

In contrast, reaction of 82 with NaCN in DMF-H2O at reflux results in the formation of 7-cyano-6-nitroindole (201, 15%) and 83 (4%) as isolable products together with tar matter, and, to our surprise, 2- and/or 3-cyano-6-nitroindoles are not detected at all. When the reaction is carried out in DMSO at 150°C, only demethoxylation occurred to give 83 (62%). On the other hand, utilizing KOt-Bu and p-chlorophenoxyacetonitrile (25), the vicarious substitution reaction (87ACR282) of 82 proceeds smoothly to give a 7-cyanomethylated indole (202, 67%) (2001H1151). 

Filter, wash toluene with water, NaHC03, water and dry, evaporate in vacuum to get 100 g gamma-Cl-butyraldehyde (I) (can distill 28/2). 10 g (I), 20 g 3-nitro-phenylhydrazine dissolve in the minimum volume of hot ethanol containing 10% glacial acetic acid. Heat on steam bath one hour cool and add water until dark oil separates. Evaporate in vacuum the ethanol and decant the water to get the oily gamma-Cl-butyraldehyde-3-intro-phenylhydrazone(II). 29 g (11), 300 ml concentrated HC1, ZOO ml benzene stir three hours, replace benzene with fresh benzene and stir four hours. Combine the two benzene portions, wash with water and dry, evaporate in vacuum to get 4 g 3-(beta-Cl-ethyl)-4 and 6-nitroindole (m). 3.56 g (III), 200 ml ethanol, 200 ml 34% aqueous DMA (or other amine) and let stand at room temperature for one week. Evaporate in vacuum the ethanol, filter, dissolve the precipitate in dilute HC1 and filter. Basify the filtrate with dilute NaOH to precipitate 3 g 4 and 6-nitro-DMT (IV). 5.2 g (IV), 350 ml ethanol, 100 ml IN NaOH heat to 50° and add a solution of 3 g Na dithionite in 15 ml 0.2N NaOH. filter hot and evaporate in vacuum to get 2 g 4 and 6 amino-DMT (can purity by dissolving in HC1, filter, basify, extract with ether and dry and evaporate in vacuum the extract). 

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