Brodfuehrer and shaopeng wang of bristolmyers squibb described 2 the convenient scheme. 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. Pdf lewis acid catalyzed nenitzescu indole synthesis. Pdf although nenitzescu is known for several indole construction methods, he is most recognized for the reaction between benzoquinones and ethyl. The solidphase nenitzescu indole synthesis request pdf. Naturally occurring and synthetic indole containing molecules produced. The leimgruberbatcho synthesis of indole is often used to generate indoles with substituents on the carbocycle. Indole 285 was prepared via an enantioselective palladiumcatalyzed carbene insertion of. Lewis acid catalyzed nenitzescu indole synthesis wiley online. Nenitzescu synthesis an overview sciencedirect topics.
Nenitzescu indole synthesis request pdf researchgate. The synthesis of indole derivatives has been and continue to be a topic of research interest from well over a century 1. The nenitzescu synthesis is specific for 5hydroxyindoles section 3. Mechanism of the nenitzescu indole synthesis and its utilization for. Polarized ketene n,n and s,nacetals as novel enamine components for the nenitzescu indole synthesis full text.
Onepot synthesis of 2aminoindole3carboxamide and analogous. A novel method for lewis acid catalyzed nenitzescu indole syntheses of 5. Indole synthesis something old, something new chemical. Fischer indole synthesis the conversion of aryl hydrazones to indoles. Onepot synthesis of an indolesubstituted 7,8dicarbanido. Nenitzescu indole synthesis major reference works wiley. Volume 49, issue 50, 8 december 2008, pages 71067109. This reaction was named for its discoverer, costin neni. 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. Read lewis acid catalyzed nenitzescu indole synthesis.
Scheme 5 gargs synthesis of aspidophylline using a fischer indole approach. These metrics are regularly updated to reflect usage leading up to the last few days. Sundbergof theuniversity ofvirginia described8 the preparation from 10 scheme 4 and cyclization of acetals, such as 11 to give the indole 12. Cornforth rearrangement hn r o co2hac 2o n o erlenmeyerplochl azlactone synthesis i. The nenitzescu indole synthesis is a chemical reaction that forms 5hydroxy indole derivatives. Herein, we would like to report a novel, straightforward, and onepot synthesis of highly substituted 2amino heteroindole3carboxamides.
This has also been accomplished in a onepot synthesis using microwave irradiation. Boruah medicinal chemistry division, north east institute of science and technology csir, jorhat 785 006, assam, india article info article history. Mechanism of the nenitzescu indole synthesis and its utilization for the. Article pdf available in journal of heterocyclic chemistry 434. The main industrial routes start from aniline via vaporphase reaction with ethylene glycol in the presence of catalysts. 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. Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. Serotonin is known to exhibit antimigrane activity, so serotoninlike compounds have been synthesized as receptor agonists for the treatment of migrane headaches.
All of theses reactions are taken from our synthesis database and the list is continually growing. 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. Some interesting enhancements have been published recently. 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. The reaction was discovered in 1883 by emil fischer. The earliest such approach is the nenitzescu indole synthesis, exemplified scheme 87 in a modern manifestation 102 by daniel m. Mar 14, 2011 herein, we would like to report a novel, straightforward, and onepot synthesis of highly substituted 2amino hetero indole 3carboxamides. Synthesis of 5hydroxyindoles by the nenitzescu reaction brought to you by the organic reactions wiki, the online collection of organic reactions jump to. The first synthesis of indole, discovered in 1883, was the. May 01, 2011 read a scalable nenitzescu synthesis of 2. An effective reductive alkylation of electrondeficient ochloroarylamines was developed.
Lewis acid catalyzed nenitzescu indole synthesis velezheva. 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. The synthesis of a series of indole and carbazole derivatives from 2fluorophenyl imines is reported. This process is experimental and the keywords may be updated as the learning algorithm improves. Onepot synthesis of an indolesubstituted 7,8dicarba. The solidphase nenitzescu indole synthesis was described by ketcha et al. 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. Article views are the countercompliant sum of full text article downloads since november 2008 both pdf and html across all institutions and individuals. Formation of isomeric indoles and reaction mechanism. Lewis acid catalyzed nenitzescu indole synthesis 873. Under an argon atmosphere, one equiv of the resin is suspended in dry thf 0. Lin and colleagues expanded the nenitzescu indole synthesis to include a wide variety. Baran, richter essentials of heterocyclic chemistryi.
The journal of organic chemistry 1980, 45 8, 14931496. As an intercellular signal molecule, indole regulates various aspects of bacterial. Aminoalkyl carbaboranes are highly reactive and versatile. Today antimigraine drugs of the triptan class are often synthesized by this method. The reaction mixture was then boiled for additional 40 60.
Indole is perhaps the single most common heterocycle in all of. Behavior of 2carbomethoxy and 2acetyl1,4benzoquinone in the nenitzescu indole syntheses. Indole project gutenberg selfpublishing ebooks read. The role of a lewis acid in the nenitzescu indole synthesis.
Type 1 synthesis scheme 1 17 17 involves aromatic ch functionalization. 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. Synthesis of indole derivatives with biological activity by. The detailed mechanism is provided for each of them and several samples are given to illustrate their synthetic usefulness. Lewis acid catalyzed rapid synthesis of 5hydroxybenzogindole scaffolds by a modi. 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. 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. 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. 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. It has a bicyclic structure, consisting of a sixmembered benzene ring fused to a fivemembered pyrrole ring. Bibliography includes bibliographical references and index. The preparation of indoles and carbazoles having carbocyclic oxygen. Lewis acid catalyzed rapid synthesis of 5hydroxybenzog.
Citations are the number of other articles citing this article, calculated by crossref and updated daily. Polarized ketene n,n and s,nacetals as novel enamine components for the nenitzescu indole synthesis. Indole is an aromatic heterocyclic organic compound with formula c 8 h 7 n. Indole and its derivatives can also be synthesized by a variety of methods. The nenitzescu indole synthesis is a chemical reaction that forms 5hydroxyindole derivatives from benzoquinone and. 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. Sep 23, 2011 type 7 includes all routes to indoles from cycloalkane derivatives. Request pdf nenitzescu indole synthesis 5hydroxylindole from condensation of pbenzoquinone and. Jan 26, 2006 read lewis acid catalyzed nenitzescu indole synthesis. The indoles must be substituted on the c3 position, but tolerate a number of substituents including esters, amides, alcohols, ethers, and aryl halides. Synthesis of indole derivatives with biological activity. Zhdankin, in handbook of heterocyclic chemistry third edition, 2010.
Synthesis of diverse indole libraries on polystyrene resin. Julaug 2006 lewis acid catalyzed nenitzescu indole synthesis 875 quinone 1 in the same solvent after introduction of a catalyst. Synthesis of 5hydroxyindoles by the nenitzescu reaction. These keywords were added by machine and not by the authors. The bischler indole synthesis9a,b is a variation on this approach. How to transfer books or pdf files to ibooks without itunes. The reaction mixture is allowed to warm to 0 c, and then a saturated aqueous solution of. Suggest a mechanism for the final stage of this reaction, which occurs spontaneously. Named reactions list the organic synthesis database. This procedure is particularly useful as an easy access to 5hydroxy indoles. 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.