DOCSLIB.ORG

Synthesis of New 2- and 3-Hydroxyquinoline- 4-Carboxylic Acid Derivatives As Potential Antioxidants

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Synthesis of New 2- and 3-Hydroxyquinoline- 4-Carboxylic Acid Derivatives As Potential Antioxidants DOI 10.1515/hc-2013-0163 Heterocycl. Commun. 2014; 20(2): 81–88 Mohammed A. Massoud, Serry A. El Bialy, Waleed A. Bayoumi* and Walaa M. El Husseiny Synthesis of new 2- and 3-hydroxyquinoline- 4-carboxylic acid derivatives as potential antioxidants Abstract: A new series of 3-aryl-2-hydroxyquinoline- derivatives are 7-chloro-4-hydroxyquinoline (6) and 7-fluoro- 4-carboxylic acids 17a,b, 2-aryl-3-hydroxyquinoline- 4-hydroxyquinoline (7), which have been characterized by 4-carboxylic acids 12a–d and their derivatives 13–16 and their antioxidant effect against free radical initiated peroxi- 18–21 were designed, synthesized and evaluated for their dation [10]. Additional synthetic quinolone derivatives with antioxidant activity using the ABTS assay method. Com- effective antioxidant activity are TA 270 (8) [11] and quin- pounds 14 and 21a,b showed good antioxidant activity, oline-3-carbohydrazides (9) [12] (Figure 1). 2-Substituted whereas the remaining compounds displayed mild to benzimidazoles were recently reported to possess antioxi- moderate activity. All compounds were characterized by dant activity [13]. Based on the previous data and literature physical and spectral data. review, new starting synthons were designed and synthe- sized: 3-aryl-2-hydroxyquinoline-4-carboxylic acids (17a,b) Keywords: ABTS assay; antioxidant; benzimidazole; quin- and 2-aryl-3-hydroxyquinoline-4-carboxylic acids (12a-d). oline-4-carboxylic acid; synthesis. Hybridization with several pharmacophoric moieties were achieved in order to explore the effect on enhancing the antioxidant activity. The following analogs were obtained: *Corresponding author: Waleed A. Bayoumi, Faculty of Pharmacy, ester derivatives ( , and ), O-acetyl derivatives Department of Pharmaceutical Organic Chemistry, 13a-d 15 18a,b Mansoura University, Mansoura 35516, Egypt, (16a-d) and O-alkyl/aralkyl derivatives (19a-d and 20a,b). e-mail: [email protected] In addition, a heterocyclic hybrid system, in which 2- or Mohammed A. Massoud, Serry A. El Bialy and Walaa M. El Husseiny: 3-hydroxyquinoline ring is hybridized at C4 with 2-benzimi- Faculty of Pharmacy, Department of Pharmaceutical Organic dazolyl ring (14 and 21a,b) was designed and synthesized. Chemistry, Mansoura University, Mansoura 35516, Egypt The effect of structural modification at C6 of the quinoline with two lipophilic groups one of which is electron donat- ing and the other is electron withdrawing (-CH3 and -Br Introduction respectively) were designed to discover their effect on poten- tiation of the antioxidant activity. The introduction of the Quinoline derivatives are an important structural moiety latter group is useful where bromo-substituent as halogen in a number of chemotherapeutic agents and biologically bonding of the type R−X···Y−R′, where the halogen X acts as active natural products. Several derivatives of cinchoninic a Lewis acid and Y can be any electron donor moiety (elec- acid (quinoline-4-carboxylic acid, 1) are important qui- trostatic attraction) has been successfully harnessed for noline derivatives, including the abandoned analgesic lead identification and optimization. In addition, halogen- agent cinchophen (2) [1] and brequinar sodium (3) that ated aromatic systems are considered as common scaffolds has been discovered as an anticancer agent [2] and later in medicinal chemistry [14, 15]. As part of this work, a series found to have immunosuppressive activity [3]. 3-Hydroxy- of quinoline derivatives were synthesized and evaluated for 2-phenylcinchoninic acid (HPC, 4) has been reported to their antioxidant activity using an improved ABTS decolori- possess antirheumatic effects [4]. Other derivatives have zation assay [16]. ABTS is 2,2′-azinobis(3-ethylbenzothiazo- been reported to show antipsychotic [5], antiallergic [6], line-6-sulfonic acid) diammonium salt. antiarthritic [7] and anxiolytic activities [8]. In addition, a series of styrylquinoline derivatives that contain a COOH group at position 7 and an OH group at position 8 of the Results and discussion quinoline moiety have been discovered as antiviral agents. An example is (E)-8-hydroxy-2-[2-(3,4,5-trihydroxyphenyl) Chemistry ethenyl]-7-quinolinecarboxylic acid (5) [9] (Figure 1). Further- more, substituted quinolones/hydroxyquinolines have been The structural core of quinoline has generally been investigated for their antioxidant activity. Among important synthesized by various conventional reactions such as 82 M.A. Massoud et al.: Hydroxyquinoline-4-carboxylic acid derivatives as antioxidants O OH O OH O ONa O OH F OH N N N F N 1 2 4 3 OH OH OH HOOC N OH OH Cl N F N OH 5 6 7 OH R O O (CH ) OH O 2 7 R=4-OH H CO N 3 N O N 5-OCH3 H 5-CH OH 3 CH3 N O HO H OCH 3 8 9 Figure 1 Biologically important hydroxyquinolines and quinolinecarboxylic acids. O R1 O O O R1 OH N H 10a,b N R2 13a-d R2 OAc O N NH 11a,b iii OH i, ii 75–79% 80–85% N iv HO O 14 77% R1 OH N v N R2 71% 12a-d O O OH 82–86% Entry 1 2 v R R i a CH3 H N b CH3 CH3 HO O 15 c Br H 1 R OCOCH3 d Br CH3 N 2 16a-d R Scheme 1 Reagents and conditions: (i) KOH, C2H5OH, H2O, reflux, 24 h; (ii) HOAc; (iii) CH3OH, H2SO4, reflux, 72 h; (iv) o-phenylenediamine, 140°C, 1–2 h; (v) 8-hydroxyquinoline, H2SO4, DMF, reflux, 72 h; (vi) HOAc/Ac2O, reflux, 48 h. Skraup, Doebner-Von Miller, Friedlander, Pfitzinger, quinoline synthesis often do not allow for adequate diver- Conrad-Limpach and Combes. These classical syntheses sity and substitution on the quinoline ring system. Among are well known and still used frequently for the prepara- the synthetic strategies which could be conceived for tion of quinoline backbone. However, these methods for the synthesis of quinoline derivatives, the Pfitzinger M.A. Massoud et al.: Hydroxyquinoline-4-carboxylic acid derivatives as antioxidants 83 O HO O O O 1 R 1 i 1 ii R O R N 80–83% 90–91% H N OH N OH Entry R1 R2 10a,b 17a,b 18a,b a CH3 CH3 iii v iv b Br CH3 88–92% 82–87% c CH3 CH2Ph 79–83% d Br CH2Ph HO O N NH O O 1 R 1 R1 R O N O R2 N O N OH O 21a,b 20a,b 19a-d Scheme 2 Reagents and conditions: (i) phenylacetic acid, NaOAc, 200°C, 3 h; (ii) CH3OH, H2SO4, reflux, 6 h; (iii) RX, CH3CN, K2CO3, reflux, 24 h; (iv) BrCH2COOC2H5, DMF, K2CO3, reflux, 24 h; (v) o-phenylenediamine, 140°C, 1–2 h. reaction offers a very convenient synthetic entry to the heating of the respective substrates 12a–d with a mixture quinoline-4-carboxylic acid derivatives from isatins and a of acetic anhydride and acetic acid (Scheme 1). Synthesis ketone. of 2-hydroxyquinoline-4-carboxylic acid derivatives 17a,b Synthesis of the substituted quinoline-4-carboxylic was achieved through reaction of isatin derivatives 10a,b acid derivatives 12a–d, which are the starting compounds and phenyl acetic acid via fusion in presence of sodium of Scheme 1, was achieved through Pfitzinger reaction by acetate as a catalyst (Scheme 2) [20]. The conversion of heating isatins 10a,b [17] with compounds 11a,b [18] in an 17a,b into their methyl esters 18a,b was achieved through aqueous/alcoholic KOH solution. The conversion of com- esterification following the same procedure already men- pounds 12a–d into their esters 13a–d was accomplished tioned for the esters 13a–d. Alkylation and aralkylation of by using Fischer esterification [19], that is, heating 12a-d compounds 18a,b at the 2-hydroxy group affording 19a,b in methanol in the presence of sulfuric acid as a catalyst was achieved through Williamson ether synthesis [21]. In and a dehydrating agent. Benzimidazole derivative 14 a similar way, alkylation of the 2-hydroxyl group of com- was obtained by conventional condensation of 12b with pounds 17a,b with ethyl bromoacetate in DMF using K2CO3 o-phenylenediamine under solvent-free condition. Esteri- as a catalyst to afford esters 20a,b [22, 23]. In addition, fication of 12b with 8-hydroxyquinoline afforded the ester treatment of the carboxylic acids 17a,b with o-phenylen- 15. O-Acetylated compounds 16a–d were obtained by ediamine furnished the respective benzimidazoles 21a,b Table 1 Results of ABTS antioxidant assay. Tested Sample % Inhibition Tested Sample % Inhibition compound absorbance compound absorbance (mean) (mean) Control 0.512 0.00 16c 0.473 7.20 ± 0.29 Ascorbic acid 0.051 90.04 ± 0.31 16d 0.466 8.97 ± 0.41 12a 0.474 7.51 ± 0.02 17a 0.504 1.65 ± 0.19 12b 0.491 4.09 ± 0.02 17b 0.490 4.29 ± 0.24 12c 0.473 7.60 ± 0.29 18a 0.491 4.19 ± 0.13 12d 0.466 8.97 ± 0.40 18b 0.436 14.82 ± 0.29 13a 0.512 0.00 ± 0.00 19a 0.446 12.87 ± 0.39 13b 0.394 23.02 ± 0.55 19b 0.458 10.63 ± 0.35 13c 0.504 1.65 ± 0.08 19c 0.290 43.41 ± 0.24 13d 0.504 1.65 ± 0.18 19d 0.335 34.53 ± 0.47 14 0.048 96.00 ± 0.52 20a 0.266 48.09 ± 0.45 15 0.466 8.97 ± 0.45 20b 0.114 77.65 ± 0.87 16a 0.458 10.63 ± 0.57 21a 0.050 93.00 ± 0.64 16b 0.473 7.20 ± 0.19 21b 0.049 94.00 ± 0.55 Data are expressed as mean ± SEM, n = 3; SEM is standard error of the mean.
Load more

Recommended publications
  • Carla Brown Phd Thesis V5
    DESIGN AND SYNTHESIS OF NOVEL SMALL-MOLECULE ANTIMICROBIALS DESIGN AND SYNTHESIS OF NOVEL SMALL-MOLECULE ANTIMICROBIALS By CARLA E. BROWN, B. Art. Sc., M. Sc. A Thesis Submitted to the School of Graduate Studies in Partial Fulfilment of the Requirements for the Degree Doctor of Philosophy McMaster University © Copyright by Carla E. Brown, June 2017 Ph.D. Thesis – C. Brown; McMaster University – Chemistry and Chemical Biology McMaster University DOCTOR OF PHILOSOPHY (2017) Hamilton, Ontario (Chemical Biology) TITLE: Design and Synthesis of Novel Small-molecule Antimicrobials AUTHOR: Carla E. Brown, BArtSc. (McMaster University), M.Sc. (University of Toronto) SUPERVISOR: Professor James McNulty NUMBER OF PAGES: xiii, 281 ii Ph.D. Thesis – C. Brown; McMaster University – Chemistry and Chemical Biology There is a need to discover new antimicrobial drugs to combat drug-resistant infections. We are trying to find new molecules that can prevent the growth of parasites and viruses by developing and using novel chemical reactions, as well as by isolating new products from plants and fungi. This text describes a new way to make quinolines, a type of molecule found in many drugs. A molecule prepared by this method inhibited the parasite T. gondii at low concentrations. We have also identified quinazolinones, molecules that can be rapidly assembled by combining three components, which inhibit parasites and viruses. The thesis also includes a faster way to make derivatives of an antiviral molecule from daffodils, which can help determine which parts of the molecule are important for antiviral activity. We have also identified new molecules from the fungus Xylaria polymorpha and an antiviral compound from the Ficus benjamina tree.
    [Show full text]
  • Downloaded on 2017-02-12T13:48:37Z
    Title Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents Author(s) Greaney, Kieran Publication date 2014 Original citation Greaney, K. 2014. Synthesis and evaluation of novel quinolines and quinazolinediones as potential anti-cancer agents. PhD Thesis, University College Cork. Type of publication Doctoral thesis Rights © 2014, Kieran Greaney. http://creativecommons.org/licenses/by-nc-nd/3.0/ Embargo information Please note that Chapters 4-8 (pp.87-262) and Appendices (pp.I-XXIII) are unavailable due to a restriction requested by the author. Embargo lift date 2018-11-05T12:28:56Z Item downloaded http://hdl.handle.net/10468/2042 from Downloaded on 2017-02-12T13:48:37Z Synthesis and Evaluation of Novel Quinolines and Quinazolinediones as Potential Anti-Cancer Agents Kieran Greaney, B.Sc. Thesis presented for the degree of Doctor of Philosophy to National University of Ireland, Cork. Department of Chemistry Supervisor: Dr. Florence McCarthy Head of Department: Prof. Martyn Pemble May 2014 Table of Chapters Acknowledgements iii Declaration iv Abstract vi Abbreviations viii 1.0 Biological Introduction 12 2.0 Quinoline Chemical Introduction 37 3.0 Quinazoline Chemical Introduction 62 4.0 Aims and Objectives 87 5.0 Chemical Results and Discussion 94 6.0 Biological Results and Discussion 178 7.0 Current Perspectives 196 8.0 Experimental 204 9.0 References 263 Appendices Acknowledgements To express my thanks through words seems such an injustice but I’ll give it my best shot. First and foremost I would like to express my deepest gratitude to Dr. Florence McCarthy whose guidance and support during this project has been nothing short of immense, and for having me as part of such a great research group.
    [Show full text]
  • I Dedicate This Work with Deep Love and Respect to the Soul of My Father
    Dedication I dedicate this work with deep love and respect to The soul of my father, To my mother My brother My sisters And to my friends. I Acknowledgments Praise be to Allah the Almighty to all his blessing to us, and I would like to express my sincere gratitude and appreciation to my supervisor: Prof. Dr. Ahmed Elsadig Mohammed Saeed, for suggesting the idea of this work and guidance during all stages of research, and my deep gratefulness to my Co-supervisor: Dr. Amna Bintwahab Elrashid Mohammed, my gratitude goes also to Dr. Rafee Eljack, Dr. Abubaker Mohammed Osman, Rami Baha Aldin for 1H and 13CNMR analysis and Valantina for helping me to analyize my samples, my deep gratefulness to the staff of laboratory techniques for their help, and to all my colleagues in the research lab, and my sincere thanks to my family for their love and support. II Abstract A series of some new substituted quinolines were synthesized by Doebner reaction, a three component coupling of various aromatic amines with two aldehydes and phenyl pyruvic acid. The substituted 2,3-diary-6-acetyl-quinoline-4-carboxylic acids reacted with various aromatic aldehydes in the presence of basic medium using Claisen-Schmidt condensation to afford the corresponding chalcones. The substituted chalcones, on condensation with hydroxylamine hydrochloride in ethanol furnished isoxazoles derivatives. Other quinoline derivatives were synthesized in this study by using an aryl amine with acetylacetone as Combes reaction, Knorr reaction between aryl amine and ethylacetoacetate with heating above 100ºC and Conrad-Limpach quinoline synthesis a thermal condensation of aryl amine with ethylacetoacetate.
    [Show full text]
  • Synthesis of Isatine Derivatives Considering Pfitzinger Reaction Part I
    International Journal of Science and Research (IJSR) ISSN (Online): 2319-7064 Index Copernicus Value (2013): 6.14 | Impact Factor (2013): 4.438 Synthesis of Isatine Derivatives Considering Pfitzinger Reaction Part I Prof. Dr. Mohammad Mahdi Saleh1, Marwa Ibrahim Khaleel2 1, 2Department of Chemistry, College of Science for Women, Baghdad University Abstract: In this work neuteric quinoline-4- carboxylic acid derivatives have been compilation from isatin. Onset, quinoline -4- carboxylic derivatives were designed from the reaction of isatin with different ketone (benzophenone, acetylacetone and acetone) in presence of powerful base (KOH) under Pfitzinger reaction case to obtain corresponding derivatives (1-3). Secondly, derivatives (4-6) have prepared by reflux of compounds (1-3) with p-hydroxybenzaldehyde in presence of few drops of concentrated sulfuric acid, and then the products were refluxed respectively with guanine to give desired compounds (7-9). Furthermore, carboxamide derivatives (10- 12) have been prepared by refluxing of compounds (1-3) with o-phenylenediamine (benzene-1, 2-diamine) in ethanol solvent. Finally, derivatives (16-18) have been prepared by reaction of synthesized derivatives (13-15) that prepared from the reaction of compounds (1 - 3) with thionyl chloride followed by conversion into corresponding quinoline-8-yl (substituted quinoline-4- carboxylic acid (16-18) by reaction with quinolin-8-ol in acetone. All structures of newly synthesized compounds have been characterize and identified via of their physical properties and spectral data analysis (1H-NMR, FT-IR and U.V.). Keywords: Pfitzinger reaction, powerful base, o-phenylenediamime, quinoline-8-yl, thionyl chloride. 1. Introduction Synthesis of {2, and 2, 3-substitutedlquinoline-4-carboxylic acid} (1-3)[14]: The quinoline nucleus [1, 2, 3] is an important structural A ( 5.9 g, 0.01 mol) of potassium hydroxide was dissolved in moiety on a number of kink chemotherapeutic agents.
    [Show full text]
  • Skraup-Doebner-Von Miller Quinoline Synthesis
    SCIENTIFIC LETTER 15 1 2-12 Modifier le style Modifier le style Edito des sousScience-titres des sous-titres Traditional methods for ATLANCHIM PHARMA synthesisdu masque of quinolines du masque Edito Editorial Dans le contexte sanitaire que nous avons tous connus en In the health context that we have all experienced throughout 2020 et en ce début 2021 notre équipe a dû et a su 2020 and beginning of 2021, our team had and managed to s’adapter à ces nouvelles conditions de travail et a continué adapt to these new working conditions and ensured the d’assurer la livraison de vos projets. Ainsi en 2020, 85% des achievement of your projects. In 2020, 85% of contracts were contrats ont été livrés dans les délais impartis et ce malgré delivered on time, despite a very specific context. un contexte sanitaire très particulier et contraignant. We fully appreciate the efforts you had to make yourself to Nous mesurons pleinement les efforts que vous avez dû maintain your R&D projects and we are proud to have been réaliser pour maintenir vos projets de recherche et nous able to participate alongside you in the synthesis of these new sommes fiers d’avoir pu participer à vos côtés à la synthèse chemical entities, some of which meet the challenges to be de ces nouvelles entités chimiques, qui pour certaines taken up in the fight against COVID. répondent aux défis à relever dans la lutte contre le COVID. You have trusted us during this period, and we are delighted Vous nous avez fait confiance tout au long de cette période to announce the new arrival of three chemists who have aussi nous sommes ravis de vous annoncer l’arrivée ces joined our team : Dr.
    [Show full text]
  • Metal-Free Domino One-Pot Protocols for Quinoline Synthesis †
    RSC Advances This is an Accepted Manuscript, which has been through the Royal Society of Chemistry peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, before technical editing, formatting and proof reading. Using this free service, authors can make their results available to the community, in citable form, before we publish the edited article. This Accepted Manuscript will be replaced by the edited, formatted and paginated article as soon as this is available. You can find more information about Accepted Manuscripts in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or graphics, which may alter content. The journal’s standard Terms & Conditions and the Ethical guidelines still apply. In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/advances Page 1 of 35RSC Advances RSC Advances Dynamic Article Links ► Cite this: DOI: 10.1039/c0xx00000x www.rs c.org/xxxxxx REVIEW Metal-free domino one-pot protocols for quinoline synthesis † Jaideep B. Bharate, ab Ram A. Vishwakarma, ab * Sandip B. Bharate ab * Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX DOI: 10.1039/b000000x 5 Quinoline is one of the most widely investigated scaffold by camptothecin analogues namely topotecan and irinotecan have synthetic chemists because of its medicinal importance. The been approved for clinical use for cancer chemotherapy, 34 and wide range of metal-catalyzed, metal-free, multi-step or another analog exatecan is under clinical studies.
    [Show full text]
  • Synthesis of Novel Glycosylidene-Based Quinolines Peter H
    Seton Hall University eRepository @ Seton Hall Seton Hall University Dissertations and Theses Seton Hall University Dissertations and Theses (ETDs) 2010 Synthesis of Novel Glycosylidene-Based Quinolines Peter H. Dobbelaar Seton Hall University Follow this and additional works at: https://scholarship.shu.edu/dissertations Part of the Organic Chemistry Commons Recommended Citation Dobbelaar, Peter H., "Synthesis of Novel Glycosylidene-Based Quinolines" (2010). Seton Hall University Dissertations and Theses (ETDs). 1483. https://scholarship.shu.edu/dissertations/1483 Synthesis of Novel Glycosylidene-Based Quinolines A Dissertation In The Department of Chemistry and Biochemistry submitted to the faculty of the Graduate School of Arts and Sciences in partial fulfillment of the requirements for the degree of Doctor of Philosophy In Chemistry Seton Hall University by Peter H. Dobbelaar May 2010 We certify that we have read this thesis and that in our opinion it is adequate in scientific scope and quality as a dissertation for the degree of Doctor of Philosophy. APPROVED Signature 3.Q> Dr. Cecilia H. Marzabadi, Advisor -TI-6 Ity, Reader and Department Chair Approved for the Department of Chemistry and Biochemistry Acknowledgements I owe a debt of gratitude to my graduate advisor, Dr. Cecilia H. Marzabadi, for her guidance during my studies at Seton Hall University. In addition, I am also grateful for the support of my supervisors, Maryadele J. O'Neil and Patricia E. Heckelman, both of The Merck Index, as well as Dr. Cherie B. Koch, my previous supervisor and a former Merck Index editor. Their backing was pivotal in obtaining financial assistance through The Merck Research Laboratories Doctoral Program.
    [Show full text]
  • A Study of Steric Inhibition of the Pfitzinger Reaction
    University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Masters Theses Graduate School 6-1949 A Study of Steric Inhibition of the Pfitzinger Reaction Robert Earl Stobaugh University of Tennessee, Knoxville Follow this and additional works at: https://trace.tennessee.edu/utk_gradthes Part of the Chemistry Commons Recommended Citation Stobaugh, Robert Earl, "A Study of Steric Inhibition of the Pfitzinger Reaction. " Master's Thesis, University of Tennessee, 1949. https://trace.tennessee.edu/utk_gradthes/4829 This Thesis is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Masters Theses by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a thesis written by Robert Earl Stobaugh entitled "A Study of Steric Inhibition of the Pfitzinger Reaction." I have examined the final electronic copy of this thesis for form and content and recommend that it be accepted in partial fulfillment of the equirr ements for the degree of Master of Science, with a major in Chemistry. George P. Mueller, Major Professor We have read this thesis and recommend its acceptance: Calvin Buehler, George K. Schweitzer Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) May 14, 1949 To the.Committee on Graduate Study: I am submitting to you a thesis written by �obert Earl Stobaugh entitled "A Study of Steric Inhibition of the Pfitzinger Reaction." I recommend that it be accepted for nine quarter hours of credit in partial fulfillment of the requirements for the degree of Master of Science, with a major in Chemistry.
    [Show full text]
  • Synthesis of Ferrocenyl Substituted Quinolines A
    SYNTHESIS OF FERROCENYL SUBSTITUTED QUINOLINES A THESIS SUBMITTED TO THE GRADUATE SCHOOL OF NATURAL AND APPLIED SCIENCES OF MIDDLE EAST TECHNICAL UNIVERSITY BY ÖZLEM VEL ĐOĞLU IN PARTIAL FULLFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE IN CHEMISTRY AUGUST 2008 Approval of the thesis: SYNTHESIS OF FERROCENYL SUBSTITUTED QUINOLINES submitted by ÖZLEM VEL ĐOĞLU in partial fulfillment of the requirements for the degree of Master of Science in Chemistry Department, Middle East Technical University by, Prof. Dr. Canan Özgen ____________ Dean, Graduate School of Natural and Applied Sciences Prof. Dr. Ahmet M. Önal ____________ Head of Department, Chemistry Prof. Dr. Metin Zora ____________ Supervisor, Chemistry Dept., METU Examining Committee Members: Prof. Dr. Cihangir Tanyeli __________________ Chemistry Dept., METU Prof. Dr. Metin Zora __________________ Chemistry Dept., METU Prof. Dr. Fatma Sevin Düz __________________ Chemistry Dept., Hacettepe University Assist.Prof. Dr. Barı ş Yücel __________________ Chemistry Dept., Đstanbul Technical University Assist. Prof. Dr. Adnan Bulut __________________ Chemistry Dept., Kırıkkale University Date: 14.8.2008 I hereby declare that all information in this document has been obtained and presented in accordance with academic rules and ethical conduct I also declare that, as required by these rules and conduct, I have fully cited and referenced all material and results that are not original to this work. Name, Last Name: Özlem Velio ğlu Signature : iii ABSTRACT SYNTHESIS OF FERROCENYL SUBSTITUTED QUINOLINES Velio ğlu, Özlem M.S., Department of Chemistry Supervisor: Prof. Dr. Metin Zora August 2008, 61 pages Quinolines have been studied for over a century as an important class of heterocyclic compounds and continue to attract considerable interest due to the broad range of biological activities they possess.
    [Show full text]
  • Recent Advances in Metal-Free Quinoline Synthesis
    molecules Review Recent Advances in Metal-Free Quinoline Synthesis Ginelle A. Ramann and Bryan J. Cowen * Department of Chemistry and Biochemistry, University of Denver, Denver, CO 80208, USA; [email protected] * Correspondence: [email protected]; Tel.: +1-303-871-2981; Fax: +1-303-871-2254 Academic Editor: Wim Dehaen Received: 27 June 2016; Accepted: 22 July 2016; Published: 29 July 2016 Abstract: The quinoline ring system is one of the most ubiquitous heterocycles in the fields of medicinal and industrial chemistry, forming the scaffold for compounds of great significance. These include anti-inflammatory and antitumor agents, the antimalarial drugs quinine and chloroquine, and organic light-emitting diodes. Quinolines were first synthesized in 1879, and since then a multitude of synthetic routes have been developed. Many of these methods, such as the Skraup, Doebner–Von Miller, and Friedlander quinoline syntheses, are well-known but suffer from inefficiency, harsh reaction conditions, and toxic reagents. This review focuses on recent transition metal-free processes toward these important heterocycles, including both novel routes and modifications to established methods. For example, variations on the Skraup method include microwave irradiation, ionic liquid media, and novel annulation partners, all of which have shown increased reaction efficiency and improved yield of the heteroring-unsubstituted quinoline products. Similarly, modifications to other synthetic routes have been implemented, with the quinoline products displaying a wide variety of substitution patterns. Keywords: quinoline; heterocycle; metal-free 1. Introduction Quinoline was discovered by Runge in 1834 as one of the many components extracted from coal tar [1]. While this nitrogen-based heterocycle is not overly useful in and of itself, it is easily modified with simple to complex functionalities, giving a multitude of compounds that are ubiquitous in the fields of medicinal and industrial chemistry.
    [Show full text]
  • 1.5.5 Knorr Quinoline Synthesis
    Introduction 1.1Quinoline: Is a heterocyclic aromatic organic compound with the chemical formula C9H7N.Quinoline structure composed of benzene and pyridine ring at two adjacent carbon atoms. 1.2 Quinolines: Quinoline derivatives are prevalent in variety of pharmacologically active synthetic and natural compounds. 1.3 Occurrence and isolation: Quinoline is present in small amount in crude oil within the virgindiesed fraction. It can be removed by hydro treating often with anickel-molybedeum an alumina . Quinoline was first extracted from coal tar (is brown or black liquid of extremely high viscosity). In 1834 by Friendlier Ferdinand Rung. Coal tar remains the principle source of commercial quinoline. 1.4 Physical properties of quinoline: Is colorless aged sample,if exposed to light, becomes yellow and later brown. Hydroscopic liquid with strong odor. Slightly soluble in cold water but dissolve in hot water and most organic solvent. 1 1.5 Synthetic methods for preparation quinoline: 1.5.1 CONRAD-LIMPACH SYNTHESIS: Is the condensation of aniline with B-keto ester to form 4-hydroxy quinoline via a Schiff base. The overall reaction type is a combination of both an addition reaction as well as rearrangement reaction was discovered by Max Conrad (1848-1920) and Leonhard Limpach (1852- 1933) in 1887 while they were studying the synthesis of quinoline derivatives. O OH O 1 O R2O R H 1 2 R OR 1 NH2 R N N O OH O 1 O R2O R H 1 2 R OR 1 NH2 R N N OR2 O O OH O O H NH2 H R1 R1 OR2 R1 OR2 N O- H2 OR2 O OH R2O R2O O H H2O R1 N OH N R1 N 1 H H R H H HO OR2 H O OR2 O H R2OH 1 N R N R1 N R1 H H H OH OH 1 R1 N R N H 2 The mechanism begins with an attack of aniline on the keto group of the keto group of B-keto ester, the newly formed oxide is then twice protonated to form the Schiff base , which then undergoes keto-enol tautomerization before an electro cyclic ring closing .
    [Show full text]
  • A New Practical and Efficient One-Pot Synthesis of Polyfunctionalized Quinolines from Β-Nitroacrylates Under Heterogeneous Conditions
    A new practical and efficient one-pot synthesis of polyfunctionalized quinolines from β-nitroacrylates under heterogeneous conditions Alessandra Giardinieri Thesis to obtain the Master of Science Degree in Chemistry and Advanced Chemical Methodologies Supervisors: Prof. Roberto Ballini, Prof. Alessandro Palmieri Co-Supervisor: Dr. Susanna Sampaolesi Examination Committee Presidente: Prof. Maria Isabel Delgado Jana Marrucho Ferreira Supervisor: Prof. Alessandro Palmieri Members of the Committee: Prof. John Paul Nunes Cabral Telo June 2017 Index Abstract .................................................................................................................................................1 1. Nitrogen-containing heterocycles ................................................................................................2 1.1 Pyrrole ...................................................................................................................................3 1.2 Imidazole ...............................................................................................................................4 1.3 Pyridine .................................................................................................................................5 1.4 Diazines .................................................................................................................................6 1.5 Indole ....................................................................................................................................7
    [Show full text]