These chapters give comprehensive coverage of all the methods of the synthesis of quinoxalines and the important quinoxalinecontaining ring systems such as thiazolo3,4 a, pyrrolo1,2 a, and imidazo1,5 aquinoxalines. This is a pdf file of an unedited manuscript that has been accepted for publication. If the inline pdf is not rendering correctly, you can download the pdf file here. It is rare in natural state, but their synthesis is easy to perform.
Natural products containing quinoxaline ring are rare and can be easily prepared or synthesized. The discovery of quinoxalinebased metathesis catalysts. Sequential synthesis, olfactory properties, and biological activity of. Abouzid 5,8, 1 pharmaceutical organic chemistry department, faculty of pharmacy, october university for modern. Quinoxaline itself prepared by the condensation of ophenylene diamine with glyoxal sodium bisulphite in 8590% yield29. Quinoxalines and fused ring systems show diverse pharmacological activities. Synthesis of naphthoquinoxaline7, 12dione, anthraptereidine7, 12. Onepot and efficient protocol for synthesis of quinoxaline derivatives mohammad reza islami and zahra hassani department of chemistry, shahid bahonar university, kerman, iran p. Design and synthesis of new quinoxaline derivatives as.
An expedient and concise ugibased unified approach for the rapid assembly of quinoxaline frameworks has been developed. The quinoxaline synthesis involving the reaction of substituted ophenylenediamines and 1, 2diketones is illustrated in reaction scheme 1. As potential antiinflammatory and analgesic activity. Quinoxaline derivatives are an important class of heterocycle compounds, where n replaces some carbon atoms in the ring of naphthalene. Several fused triazolo and ditriazoloquinoxaline derivatives such as 1aryl4 chloro1,2,4triazolo 4,3aquinoxalines 3ad, 4alkoxy1,2,4triazolo4. Progress in quinoxaline synthesis part 2 request pdf.
Onepot and efficient protocol for synthesis of quinoxaline. Quinoxaline and its derivatives are important structural units for the development of. Synthesis, reactions and biological activity of quinoxaline derivatives. We report a suitable quinoxaline synthesis using molybdophosphovanadates supported on commercial alumina cylinders as catalysts. The full text of this article is available in pdf format. Compounds 3a3i were obtained by the condensation of o phenylenediamines with 1,2. Benzil quinoxaline synthesis cameron trefny jason young tth 5. Synthesis of 4h2acetylnaphtho2,3f quinoxaline3,7,12 trione 4 a mixture of 2 2 g, 8 mmol and ethylacetoacetate 1 ml, 8 mmol in 30 ml dimethylformamide containing 0. A new approach for the formation of quinoxaline derivatives indolo 2, 3. Quinoxaline2carboxaldehyde was also used for the synthesis of a large number of new condensed quinoxalines and heteroaryl quinoxalines. A literature search has revealed that synthesis of quinoxalines substituted with an indene. Although quinoxaline itself is mainly of academic interest, quinoxaline.
Progress in quinoxaline synthesis part 1 request pdf. Recent trends in synthesis of quinoxaline and its derivatives. View the article pdf and any associated supplements and figures for a period of 48 hours. Therefore, the condensation of ophenylenediamine with adicarbonyl compounds results in quinoxaline formation fig. The catalyst is recyclable and reusable 2006 published by elsevier b. Pdf green synthesis of quinoxaline derivatives researchgate. Malononitrile, pyrazolone, spiro indeno1,2b quinoxaline, 1,2phenylenediamine, ninhydrine. Cshaped diastereomers containing cofacial thiophene. The chemical synthesis was initiated with the reaction of ophenylenediamine 1 with ethyl pyruvate in nbutanol to yield 2hydroxy3methylquinoxaline 2, which on treatment with pocl 3 yielded 2chloro3methylquinoxaline 3. A quinoxaline, also called a benzopyrazine, in organic chemistry, is a heterocyclic compound containing a ring complex made up of a benzene ring and a pyrazine ring. Pdf a simple and catalyst free synthetic method has been developed by the synthesis of quinoxaline derivatives from 2chloro quinoxaline.
Synthesis of sulfonamide derivatives of quinoxaline synthesis of 2, 3diphenyl, 7sulfonamido quinoxaline l1 sulfonylchloride quinoxaline derivative was refluxed with 50% 30 ml nh 3 solution for 1. Pdf the objective of present research work is to provide green technique for synthesis of 2,3diphenyl quinoxaline. Its molecular formula is c 8 h 6 n 2, formed by the fusion of two aromatic rings, benzene and pyrazine. Progress in quinoxaline synthesis part 2 sciencedirect. Quinoxaline and its derivatives are attractive chemical candidates in medicinal chemistry. Direct synthesis of novel quinoxaline derivatives via. Consequently, a large variety of synthetic methods for the synthesis of functionalized quinoxalines have been reported in. The present paper describes the synthesis and antibacterial activity of sixteen new quinoxaline5carboxamide derivatives 5a5p from commercially available methyl 2, 3diamino benzoate as. The method shows high yields of quinoxaline derivatives under.
Quinoxaline is prepared by the reaction of ophenylenediamine with glyoxal. The first four chapters present a survey of the developments in quinoxaline chemistry since the publication of the monograph on condensed pyrazines by cheeseman and cookson in 1979. A onepot threecomponent reactions for the synthesis of fully. Setiz le, suling wj, reynolds rc 2002 synthesis and antimycobacterial activity of pyrazine and quinoxaline derivatives.
The synthesis of quinoxalines has been intensively studied in the past, especially because of the diverse biological activities ascribed to many representatives of this class of compounds. For more information, read michigan publishings access and usage policy. Synthesis of 1,4dihydroquinoxaline2,3 dione 1 1,4dihydroquinoxaline2,3 dione 1 was prepared. It is isomeric with other naphthyridines including quinazoline, phthalazine and cinnoline. This convergent and versatile method uses readily available commercial reagents, does not require advanced intermediates, and exhibits excellent bondforming efficiency, thus exemplifying the operationally simple synthesis of quinoxaline libraries. Compound 1 was prepared according to previously reported procedures by condensation of commercially available 2,3dichloroquinoxaline with malononitrile in the presence of sodium hydride. This work is licensed under a creative commons attributionnoncommercial 3. Thus, the development of environmentally friendly benign green chemistry, highyielding and clean approaches for the synthesis of quinoxaline derivatives is still remains a highly desired goal in organic synthesis. General procedure for synthesis of quinoxaline derivatives 2af. Yingjun xu et al49 synthesized quinoxaline 1,4 dinoxide derivatives by the treatment of 5sub benzoc1,2,5oxadiazole 1oxide4 with methyl carbonic propionic anhydride5 in presence of sodium hydride in thf yields quinoxaline 1,4 dinoxide derivatives6 scheme 2. Synthesis of highly functionalized polycyclic quinoxaline derivatives using visible. Bioinspired orthoquinone catalysts have been applied to oxidative synthesis of benzimidazoles, quinoxalines and benzoxazoles from primary amines in high yields under mild conditions with oxygen as the terminal oxidant. The reaction proceeds with operational simplicity, an easily available catalyst system, and.
A literature survey indicates that quinoxaline derivatives possess different. This reaction proceeds via imine formation, cyclisation, and oxidation in one. Synthesis and antimicrobial activities of some novel. A series of pyrazine and quinoxaline probes qnns were synthesized and evaluated. A mixture of compound 3 and 4hydroxy benzaldehyde was next refluxed in acetonitrile for 30 hours to afford 2pformylphenoxy3methyl quinoxaline. Sigmaaldrich offers a number of quinoxaline products. It is a colorless oil that melts just above room temperature. Numerous methods are available for the synthesis of quinoxa. Pyrrolo3,2 bquinoxaline derivatives as types i and ii. The synthesis of 1hpyrrolo2,3bquinoxaline derivatives 6 and 7 is shown in scheme 1. Chung, andrew brunskill, louischarles campeau, and mark mclaughlin department of process and analytical chemistry, merck research laboratories, rahway, new jersey 07065, usa supporting information. Then reaction mixture was cooled and poured into water to get sulfonamide derivative of 2, 3diphenylquinoxaline. To synthesize benzil quinoxaline from benzil and ophenylenediamine in a condensation, double imine formation reaction. Synthesis of nheterocycles benzofused nheterocycles synthesis of quinoxalines.
The cdk15 inhibitor, also referenced under cas 40254908, controls the biological activity of cdk15. Files available from the acs website may be downloaded for personal use only. Synthesis of certain substituted quinoxalines as antimicrobial agents. Exploring biological activities of quinoxaline derivatives. Synthesis and characterization of two diastereomeric cshaped molecules containing cofacial thiophenesubstituted quinoxaline rings are described. The structure of quinoxaline derivatives were confirmed by using ir, 1hnmr, mass spectroscopy.
Quinoxaline 2carboxaldehyde was also used for the synthesis of a large number of new condensed quinoxalines and heteroaryl quinoxalines. Efficient assembly of quinoxaline derivatives from benzene1,2. It is rare in natural state, but their synthesis is easily to perform1. Facile method of quinoxaline synthesis using phenol as a. It is a mancude organic heterobicyclic parent, an orthofused heteroarene and a naphthyridine. Synthesis and evaluation of quinoxaline derivatives as potential. Design and syntheses of some new quinoxaline derivatives. The discovery of quinoxalinebased metathesis catalysts from synthesis of grazoprevir mk5172 michael j. Introduction quinoxaline derivatives are a very important class of nitrogencontaining compounds and have been widely used in. A number of synthetic methods are available for the synthesis of 1 and its derivatives. Syntheses of quinoxaline derivatives via many different methods of synthetic strategies have been presented. The catalytic test was performed under different reaction conditions in order to know the performance of the synthesized catalysts.
The common procedure for their synthesis consists of condensing odisubstituted benzene with a two carbon synthon. Design and synthesis of new quinoxaline derivatives as anticancer agents and apoptotic inducers aliya m. This article describes the synthesis of new bioactive quinoxalines as potential anticancer and antimi crobial agents. Synthesis of quinoxaline and its derivatives scheme 1.
Quinoxaline is a naphthyridine in which the nitrogens are at positions 1 and 4. The quinoxaline derivative 3b, with high affinity and selectivity for tau aggregates, favorable fluorescence turnon capability and brain kinetics, was successfully applied to the detection of tau tangles both in vitro and in. Condensed quinoxalines were obtained by oxidative cyclisation of quinoxaline2carboxaldehyde hydrazone and phenylhydrazone using lead tetraacetate. Synthesis and evaluation of pyrazine and quinoxaline. These catalysts were prepared by incipient wetness impregnation. The synthesis of quinoxaline derivatives starting from 2. Synthesis of highly functionalized polycyclic quinoxaline. N n quinoxaline o o ch3 ch3 butane2,3dione nh2 nh2 benzene1,2diamine scheme 1. The most common method is condensation of an aryl 1,2diamine with 1,2dicarbonyl compound in suitable solvent 19, 20 scheme1. Here, a palladiumcatalyzed new hydrogenative annulation reaction of catechols and nitroarylamines, allowing straightforward access to two classes of novel quinoxaline derivatives, is reported. Compounds 156 158 and 162 164 were subsequently synthesized starting from 2halo n alkyl5nitroanilines 168a d according to the pathways shown in scheme 17. Facile synthesis of quinoxaline derivatives using o. Synthesis of 1,4dihydroquinoxaline2,3dione 1 1,4dihydroquinoxaline2,3dione 1 was prepared.
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