Synthesis of diverse indole libraries on polystyrene resin. 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 degree of master of science. Application to the synthesis of indolefused compounds shuchen lin, fwuduo yang, jiannshyng shiue, shyhming yang, and jimmin fang the journal of organic chemistry 1998 63 9, 29092917. Serotonin is known to exhibit antimigrane activity, so serotoninlike compounds have been synthesized as receptor agonists for the treatment of migrane headaches. Application to the synthesis of indole fused compounds shuchen lin, fwuduo yang, jiannshyng shiue, shyhming yang, and jimmin fang the journal of organic chemistry 1998 63 9, 29092917. The synthesis of 5hydroxyindole and 5hydroxybenzofuran derivatives by the condensation of quinones with various enamines the nenitzescu reaction. It has a bicyclic structure, consisting of a sixmembered benzene ring fused to a fivemembered nitrogen containing pyrrole ring. 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 preparation of indoles and carbazoles having carbocyclic oxygen. Jul 01, 2006 a novel method for lewis acid catalyzed nenitzescu indole syntheses of 5. Mechanism of the nenitzescu indole synthesis and its utilization for the. Suggest a mechanism for the final stage of this reaction, which occurs spontaneously. These keywords were added by machine and not by the authors. Synthesis of indole derivatives with biological activity by.
Mechanism of the nenitzescu indole synthesis and its utilization for the preparation. Biographical sketches for the chemists who discovered or developed those name reactions have been included. This procedure is particularly useful as an easy access to 5hydroxy indoles. The leimgruberbatcho synthesis of indole is often used to generate indoles with substituents on the carbocycle. Pdf 1181 kb supporting information publication date. Sundbergof theuniversity ofvirginia described8 the preparation from 10 scheme 4 and cyclization of acetals, such as 11 to give the indole 12. The method is simple, rapid, efficient, and allows preparation of hydroxyindoles from 1,4. Velezheva, valeriya s kornienko, albert g topilin, sergey v turashev, ascar d peregudov, alexander s brennan, patrick j. 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.
This extensive volume concludes with the modern transition metalcatalyzed indole ring syntheses that utilize copper, palladium, rhodium, gold, ruthenium, platinum, and other metals to fashion the indole ring. The solidphase nenitzescu indole synthesis sciencedirect. Bromosuccinimide, 820 nbs, 820 nbutyl tin hydride, 733 nchlorosuccinimide, 82 1 nchlorosuccinimidedimethyl sulfide, 744 ncs, 744,821,841 neber rearrangement, 450 nef reaction, 452 negishi coupling, 274,454 nencki reaction, 254 nenitzescu reductive acylation, 456 nenitzescu indole synthesis. The synthesis of a series of indole and carbazole derivatives from 2fluorophenyl imines is reported. The solidphase version of the nenitzescu indole synthesis of 5hydroxyindole3carboxamides is reported. A novel method for lewis acid catalyzed nenitzescu indole syntheses of 5.
Indole is widely distributed in the natural environment and can be produced by a variety of bacteria. Scheme 5 attempted introduction of a bromo or hydroxymethyl group at indole derivative 4, which resulted in the formation of a methyl. Synthesis of 5and 6hydroxyindole derivatives by the. Mechanism of the nenitzescu indole synthesis and its utilization for. Onepot synthesis of an indolesubstituted 7,8dicarba. Cornforth rearrangement hn r o co2hac 2o n o erlenmeyerplochl azlactone synthesis i. Synthesis of 5and 6hydroxy indole derivatives by the method of nenitzescu. 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. Nenitzescu synthesis an overview sciencedirect topics. All structured data from the file and property namespaces is available under the creative commons cc0.
Please read our short guide how to send a book to kindle. Synthesis of 5hydroxyindoles by the nenitzescu reaction brought to you by the organic reactions wiki, the online collection of organic reactions jump to. Facile synthesis of 2substituted indoles and indolo3,2b. The preparation of indoles and carbazoles having carbocyclic oxygen substituents generally utilizes ring closure methods. Furthemore, the subject index is significantly expanded. Scheme 4 attempted nenitzescu indole synthesis towards an analogue of compound 2. Baran, richter essentials of heterocyclic chemistryi. 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 major alternative mechanism of the nenitzescu indole synthesis is that proposed by steck and colleagues, which involves the initial. The bischler indole synthesis9a,b is a variation on this approach. Several new name reactions and reagents are included to reflect the stateoftheart of organic chemistry.
Synthesis of 5and 6hydroxyindole derivatives by the method of nenitzescu. Synthesis and biological activities of pyrroloindazole regioisomers 4. Named reactions list the organic synthesis database. Zhdankin, in handbook of heterocyclic chemistry third edition, 2010. All of theses reactions are taken from our synthesis database and the list is continually growing. Synthesis of heteroarylogous 1hindole3carboxamidines via a. A theoretical investigation on palladiumcatalyzed onepot coupling of aryl iodides, alkynes, and amines through c n bond cleavage for the synthesis of indole derivatives nan lu, huatian wang international journal of quantum chemistry 2015 115 6, 3668. The reaction mixture is allowed to warm to 0 c, and then a saturated aqueous solution of. Indole is an aromatic heterocyclic organic compound.
Media in category cc bond forming reactions the following 200 files are in this category, out of 240 total. This has also been accomplished in a onepot synthesis using microwave irradiation. Jan 26, 2006 lewis acid catalyzed nenitzescu indole synthesis. Observations on the mechanism of the nenitzescu indole synthesis. The first synthesis of indole, discovered in 1883, was the. The detailed mechanism is provided for each of them and several samples are given to illustrate their synthetic usefulness.
Synthesis of diverse indole libraries on polystyrene resin scope and limitations of an organometallic reaction on solid supports kerstinknepper1, sylviavanderheiden2 andstefanbrase1,2 full research paper open access address. Volume 49, issue 50, 8 december 2008, pages 71067109. All types of chemical reactions in organic and inorganic. Indole is an aromatic heterocyclic organic compound with formula c 8 h 7 n. The role of a lewis acid in the nenitzescu indole synthesis. Lewis acid catalyzed rapid synthesis of 5hydroxybenzog. It occurs naturally in human feces and has an intense fecal smell.
The major alternative mechanism of the nenitzescu indole synthesis is that proposed by steck and colleagues, which involves the initial obvious condensation of. Name reactions a collection of detailed mechanisms and. The nenitzescu indole synthesis is a chemical reaction that forms 5hydroxyindole derivatives. Different from other books on name reactions in organic chemistry, name reactions, a collection of detailed reaction mechanisms focuses on their mechanisms. An effective reductive alkylation of electrondeficient ochloroarylamines was developed. 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.
Lewis acid catalyzed nenitzescu indole synthesis, journal. Lewis acid catalyzed nenitzescu indole synthesis, journal of. In the past, indoles were synthesized by using, for example, fischer indole synthesis 2630, bartoli indole synthesis, nenitzescu synthesis, wittig indole synthesis, madelung indole synthesis, palladiumcatalyzed indole synthesis 3440, cycloaddition strategies, carylation of substituted acetonitriles or 1,3dicarbonyl compounds. It can be produced by bacteria as a degradation product of the amino acid tryptophan. Jun 17, 2016 this extensive volume concludes with the modern transition metalcatalyzed indole ring syntheses that utilize copper, palladium, rhodium, gold, ruthenium, platinum, and other metals to fashion the indole ring. 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. Department of medicinal chemistry and pharmacognosy, mc 781, university of illinois at chicago, po box 6998, chicago, illinois 60680, usa. Formation of the corresponding enaminones via condensation with primary amines in the presence of trimethylorthoformate followed by addition of 1,4. The format change has doubled the space to accommodate at least two to three real case applications in synthesis for each name reaction. As an intercellular signal molecule, indole regulates various aspects of bacterial physiology, including spore. This process involves initial acetoacetylation of argopore rinknh 2 resin with diketene to afford a polymerbound acetoacetamide. The solidphase nenitzescu indole synthesis request pdf. It has a bicyclic structure, consisting of a sixmembered benzene ring fused to a fivemembered pyrrole ring. Nenitzescu indole synthesis request pdf researchgate.
This process is experimental and the keywords may be updated as the learning algorithm improves. The mechanism of a nenitzescu reaction consists of a michael addition, followed by a. A simple preparation of 2dimethylaminomethylindole, indole2acetonytrile and 22arylvinylindoles from 2methylindole is described. 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. The nenitzescu indole synthesis is a chemical reaction that forms 5hydroxyindole derivatives from benzoquinone and. Synthesis of nsubstituted indole derivatives via pifa. Synthesis of indole derivatives with biological activity. Boruah medicinal chemistry division, north east institute of science and technology csir, jorhat 785 006, assam, india article info article history. Synthesis of heteroarylogous 1hindole3carboxamidines. 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. This reaction was named for its discoverer, costin neni. The solidphase nenitzescu indole synthesis was described by ketcha et al.
Formation of isomeric indoles and reaction mechanism. Synthesis of 5hydroxyindoles by the nenitzescu reaction. The strategy exploits the ability of the indole nucleus to interrupt the classical ugi reaction, by intercepting the nascent. Formation of the corresponding enaminones via condensation with primary amines in the presence of. Lewis acid catalyzed nenitzescu indole synthesis wiley online. Synthesis of antiphlogistics in indole derivatives.
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