Fischer indole synthesis the conversion of aryl hydrazones to indoles. One of the indole synthetic approaches that is a popular name reaction is the nenitzescu indole synthesis, an easy way to indole compounds starting from enamines and quinines 92. Synthesis of indole derivatives with biological activity by. This procedure is particularly useful as an easy access to 5hydroxy indoles. These metrics are regularly updated to reflect usage leading up to the last few days. Citations are the number of other articles citing this article, calculated by crossref and updated daily. The synthesis of indole derivatives has been and continue to be a topic of research interest from well over a century 1. Herein, we would like to report a novel, straightforward, and onepot synthesis of highly substituted 2amino heteroindole3carboxamides. Pdf although nenitzescu is known for several indole construction methods, he is most recognized for the reaction between benzoquinones and ethyl. Sundbergof theuniversity ofvirginia described8 the preparation from 10 scheme 4 and cyclization of acetals, such as 11 to give the indole 12. Lewis acid catalyzed nenitzescu indole synthesis 873. C 1790% general and competitive with the fischer synthesis as a route to 2substituted indoles licl gave better results regioselective annulation larock indole synthesis i nhr 1 r 2 r 3 c at. Mar 14, 2011 herein, we would like to report a novel, straightforward, and onepot synthesis of highly substituted 2amino hetero indole 3carboxamides.
Cornforth rearrangement hn r o co2hac 2o n o erlenmeyerplochl azlactone synthesis i. Boruah medicinal chemistry division, north east institute of science and technology csir, jorhat 785 006, assam, india article info article history. The reaction mixture was then boiled for additional 40 60. Baran, richter essentials of heterocyclic chemistryi. Julaug 2006 lewis acid catalyzed nenitzescu indole synthesis 875 quinone 1 in the same solvent after introduction of a catalyst. Indole is perhaps the single most common heterocycle in all of. The bartoli indole synthesis is an organic reaction where a substituted nitroarene is converted to an indole using an excess of a vinyl grignard reagent followed by an acid workup. We tried to test whether the origin of the catalytic effect was due to enamine activation, in accordance with a hypothesis involving an enaminemichael reaction, that is, the nucleophilic addition of a coordinated enamine. Mechanism of the nenitzescu indole synthesis and its utilization for. Mechanism of the nenitzescu indole synthesis and its utilization for the. Read lewis acid catalyzed nenitzescu indole synthesis. Lewis acid catalyzed rapid synthesis of 5hydroxybenzog.
This process is experimental and the keywords may be updated as the learning algorithm improves. A novel method for lewis acid catalyzed nenitzescu indole syntheses of 5. Pdf lewis acid catalyzed nenitzescu indole synthesis. How to transfer books or pdf files to ibooks without itunes. The substituents on the nitroarene affect the yield of this reaction where the highest yields are observed for ortho substituted reagents and the bulkier groups.
An effective reductive alkylation of electrondeficient ochloroarylamines was developed. As an intercellular signal molecule, indole regulates various aspects of bacterial. The nenitzescu synthesis is specific for 5hydroxyindoles section 3. Zhdankin, in handbook of heterocyclic chemistry third edition, 2010. Formation of isomeric indoles and reaction mechanism. Lin and colleagues expanded the nenitzescu indole synthesis to include a wide variety. Suggest a mechanism for the final stage of this reaction, which occurs spontaneously. The nenitzescu indole synthesis is a chemical reaction that forms 5hydroxyindole derivatives from benzoquinone and. Article pdf available in journal of heterocyclic chemistry 434. The synthesis of a series of indole and carbazole derivatives from 2fluorophenyl imines is reported. Nenitzescu synthesis an overview sciencedirect topics. Synthesis of diverse indole libraries on polystyrene resin. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria.
Under an argon atmosphere, one equiv of the resin is suspended in dry thf 0. Nenitzescu indole synthesis therefore, in another approach the nitrogen atom was directly introduced at the carbaborane cluster as an aminomethyl group before synthetic steps towards the formation of the heterocycle by nenitzescu indole synthesis were attempted. Polarized ketene n,n and s,nacetals as novel enamine components for the nenitzescu indole synthesis full text. The preparation of indoles and carbazoles having carbocyclic oxygen. Indole can still be synthesized, however, using the fischer indole synthesis by reacting phenylhydrazine with pyruvic acid followed by decarboxylation of the formed indole 2carboxylic acid. The bischler indole synthesis9a,b is a variation on this approach. The first synthesis of indole, discovered in 1883, was the. Onepot synthesis of an indolesubstituted 7,8dicarba. Indole is an aromatic heterocyclic organic compound with formula c 8 h 7 n. Aminoalkyl carbaboranes are highly reactive and versatile. The indoles must be substituted on the c3 position, but tolerate a number of substituents including esters, amides, alcohols, ethers, and aryl halides. Type 1 synthesis scheme 1 17 17 involves aromatic ch functionalization. The synthesis of 2 and 3substituted indoles tlabo caiphus leboho a dissertation submitted to the faculty of science, university of the witwatersrand, johannesburg, in fulfilment of the requirement for the.
The role of a lewis acid in the nenitzescu indole synthesis. Jan 26, 2006 read lewis acid catalyzed nenitzescu indole synthesis. Indole synthesis something old, something new chemical. Modern versions of the classical syntheses such as the fischer synthesis, nenitzescu synthesis, ullmann reaction, leimgruberbatcho synthesis, reissert synthesis, bartoli reaction, madelung synthesis and cadogansundberg reaction are considered. However, indole on heating with acetic anhydride alone gave 1,3diacetylindole but on reaction in the presence of sodium acetate and acetic anhydride, nacetylindole was isolated. Onepot synthesis of 2aminoindole3carboxamide and analogous. The journal of organic chemistry 1980, 45 8, 14931496. Synthesis of 5hydroxyindoles by the nenitzescu reaction brought to you by the organic reactions wiki, the online collection of organic reactions jump to. Today antimigraine drugs of the triptan class are often synthesized by this method. Indole project gutenberg selfpublishing ebooks read. May 01, 2011 read a scalable nenitzescu synthesis of 2. Lewis acid catalyzed nenitzescu indole synthesis velezheva. Volume 49, issue 50, 8 december 2008, pages 71067109. Scheme 5 gargs synthesis of aspidophylline using a fischer indole approach.
Bibliography includes bibliographical references and index. Behavior of 2carbomethoxy and 2acetyl1,4benzoquinone in the nenitzescu indole syntheses. The solidphase nenitzescu indole synthesis request pdf. This has also been accomplished in a onepot synthesis using microwave irradiation. All of theses reactions are taken from our synthesis database and the list is continually growing. The fischer indole synthesis is a chemical reaction that produces the aromatic heterocycle indole from a substituted phenylhydrazine and an aldehyde or ketone under acidic conditions. The solidphase nenitzescu indole synthesis was described by ketcha et al. The main industrial routes start from aniline via vaporphase reaction with ethylene glycol in the presence of catalysts. Synthesis of 5hydroxyindoles by the nenitzescu reaction. The detailed mechanism is provided for each of them and several samples are given to illustrate their synthetic usefulness. Named reactions list the organic synthesis database. The earliest such approach is the nenitzescu indole synthesis, exemplified scheme 87 in a modern manifestation 102 by daniel m. A nenitzescu reaction has been used to prepare the indole skeleton 6 having all the functional groups necessary for its conversion into 10a, a key intermediate in a short synthesis of the.
Synthesis of indole derivatives with biological activity. Lewis acid catalyzed nenitzescu indole synthesis wiley online. Some interesting enhancements have been published recently. Request pdf nenitzescu indole synthesis 5hydroxylindole from condensation of pbenzoquinone and. Nenitzescu indole synthesis request pdf researchgate. Lewis acid catalyzed rapid synthesis of 5hydroxybenzogindole scaffolds by a modi. Brodfuehrer and shaopeng wang of bristolmyers squibb described 2 the convenient scheme. Onepot synthesis of an indolesubstituted 7,8dicarbanido. These keywords were added by machine and not by the authors.
Although ch activation is thought of as a modern topic, the venerable fischer indole synthesis still under active development, schemes 1 3 3 falls under this heading. Polarized ketene n,n and s,nacetals as novel enamine components for the nenitzescu indole synthesis. The yields of indoles 7a and 8a obtained in the presence of the more azaphilic lewis acids znc1 2 or zni 2 exceeded those achieved in the presence of oxophilic alcl 3. Naturally occurring and synthetic indole containing molecules produced.