Indole, 3-nitro

In this paper, the selectivity of the ECH method for the reduction of nitro compounds to the corresponding amines on RCu electrodes will be compared with that of reduction by RCu alloy powder in alkaline aqueous ethanol. In the latter method (termed chemical catalytic hydrogenation (CCH)), chemisorbed hydrogen is generated in situ but by reduction of water by aluminium (by leaching of the alloy) (equation [12]). The reductions by in situ leaching must be carried out in a basic medium in order to ensure the conversion of insoluble Al(OH)3 into soluble aluminate (equation [12]). The selectivity and efficiency of the electrochemical reduction of 5-nitro-indoles, -benzofurane, and -benzothiophene at RCu electrodes in neutral and alkaline aqueous ethanol will also be compared with that of the classical reduction with zinc in acidic medium. 

INDOLE, l-METHYL-3-(ll-PIPERIDYLMETHYL)-, HYDROCHLORIDE INDOLE, 3- (2-AMINOPROPYL)-ft-CHLORO-, HYDROCHLORIDE INDOLE, 2-(2-AMINOBUTYL)- -CHLORO-, HYDROCHLORIDE INDOLE, 3 (2-AMINOBUTYL)-6-CHLORO-, HYDROCHLORIDE INDOLE, 3-((DIMETHYLAMINO)METHYL)-7-NITRO-INDOLE, 3-(2-(HYDROXYAMINO)PROPYL)-, HYDROCHLORIDE, ( -)-INDOLE, 3-(2-AMINOETHYL)-5-METH0XY-, HYDROCHLORIDE INDOLE, 5-METHOXY-3- ( -PIPERIDYLMETHYL) -INDOLE, 3 (l-PHENETHYL- t-PIPERIDYLMETHYL) -... 

Russian workers have recently devised a synthesis of 2-anilino-3-nitro-indoles (14) (>75%) by reacting aromatic amines with trichloronitro-ethylene [Eq. (I)].9... 

As with pyrroles and furans, indoles undergo very few nucleophilic substitution processes. Most of those that are known involve special situations iV-substituted benzene-ring-nitro-indoles undergo vicarious nucleophilic substitutions (VNS) (3.3.3). ° Arelated process involves addition of stabilised enol(ate)s ortho to a 5-sulfoxide, with loss of the oxygen from sulfur. The reaction is highly selective for C-4, even in the presence of 3-substituents. ... 

A novel alkylation occurs at C-7 in the reaction of 4-nitro-indole with alkyhnagnesium halides. Up to the mid 1990s, the yields obtained are still rather low (Equation (13)) <94TL8553>. 

Besides the applications to synthesize ketones and esters, this reaction has been used to synthesize 7-nitro-indole by me in 1995, as shown in the following reaction route. 

Safety considerations were a driver to change the supply route in the synthesis of AZD1981 where the Makosza reaction was conducted above the flash point of acetone in the presence of air and the product nitro-indole (1, Scheme 8.2) was found to be thermally unstable. Furthermore, the yield in the first stage was low and variable (24 to 48%) impacting the overall cost and throughput. The AZ team developed a scalable, potential commercial route to AZD1981 by use of a Semmler-Wolff aromatisation of 2 to 3 to prepare the indole in 51% overall yield (Scheme 8.3). ... 

The D-ribofuranosyl hydrazine (9) can be used to produce pyrazole nucleosides such as (10) (Scheme 1) with -selectivity, and similar 2 -deoxy-compounds were also made. Ribofuranosylamine (11) (Scheme 1) can be used as a precursor of 5-substituted uridines of type (12), which can be converted to 5-carboxamidouridine (13). 3 l-p-D-Ribofuranosyl-6-nitro-indole has been made by the indole-indoline method,... 

As regards reaetions other than nitration brought about by some of these systems, especially noteworthy are the addition processes undergone by eertain indole derivatives when treated with solutions of nitrie aeid in aeetie aeid. Produets inelude glycols, nitro-alcohols, and nitro-alcohol acetates. Such additions might well be encountered with some polynuclear aromatie eompounds, and with sueh eompounds the possibility of nitration by addition-elimination must always be borne in mind. 

A solution of trifluoroacetic acid in toluene was found to be advantageous for cydization of pyruvate hydrazoncs having nitro substituents[4]. p-Toluene-sulfonic acid or Amberlyst-15 in toluene has also been found to give excellent results in preparation of indole-2-carboxylale esters from pyruvate hydra-zoiies[5,6J. Acidic zeolite catalysts have been used with xylene as a solvent to convert phenylhydraziiies and ketones to indoles both in one-flask procedures and in a flow-through reactor[7]. 

X)ml), The reaction mixture was stirred for 24 h. Nearly all of the solvent was removed in vacuo and the residue dissolved in CH2CI2. The solution was washed with 5% NHj, 1N HCl and brine. The organic layer was dried (NajSOJ and the solvent evaporated in vacuo. The residue was purified by chromatography using CHClj-hexane to give the product (28.0 g, 86%) along with a little 3-[2-nitro-2-(indol-3-ylmethyl)ethyl]indole (2.8 g. 5%). 

Indole can be nitrated with benzoyl nitrate at low temperatures to give 3-nitroindole. More vigorous conditions can be used for the nitration of 2-methylindole because of its resistance to acid-catalyzed polymerization. In nitric acid alone it is converted into the 3-nitro derivative, but in a mixture of concentrated nitric and sulfuric acids 2-methyl-5-nitroindole (47) is formed. In sulfuric acid, 2-methylindole is completely protonated. Thus it is probable that it is the conjugate acid which is undergoing nitration. 3,3-Dialkyl-3H-indolium salts similarly nitrate at the 5-position. The para directing ability of the immonium group in a benzenoid context is illustrated by the para nitration of the conjugate acid of benzylideneaniline (48). 

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