DOCSLIB.ORG

By Mehran Ali

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Use of Dimedone to Avail Various Novel Aminomethylene Compounds By Mehran Ali Department of Chemistry The Islamia University of Bahawalpur Session 2012-2014 i iii CONTENTS Page No. CHAPTER 1: SUMMARY x Chapter 1 2 INTRODUCTION 2 1.1 Dimedone 2 1.2 Physical properties of Dimedone 2 1.3 Tautomeric forms of Dimedone 3 1.4 Hydrogen bonding 3 1.5 Dimedone-Synthesis 3 1.6 Some important Reactions of Dimedone 4 1.6.1 Hantzsch reaction 4 1.6.2 Tandem Aldol-Michael reactions 4 1.6.3 Unsymmetrical Hantzsch reaction 5 1.6.4 One-pot Knoevenagel and Michael addition reaction: 5 1.6.5 Biuret reaction 6 1.6.6 Begenilli reaction 6 1.7 Importance of Dimedone 7 1.7.1 Pharmaceutical applications 7 1.7.2 In flavours and fragrance 8 1.7.3 In Laser dye and Photoinitiator 9 1.7.4 Dimedone as a probe 9 1.7.5 Dimedone as a trapper 10 1.8 Medicinal importance 10 1.8.1 Antibacterial activity 12 1.8.2 Anticonvulsant activity 12 1.8.3 Antimicrobial activity 13 1.8.4 Antioxidant properties 13 1.8.5 Antituberculosis activity 15 1.8.6 Cardiovascular activity 16 1.9 Biological importance 16 viii Chapter 2 20 LITERATURE REVIEW 20 AIM OF PROJECT 40 Chapter 3 42 EXPERIMENTAL 42 3.1 Solvents and Reagents 42 3.2 Solvents 42 3.3 Melting Point 43 3.4 Spectroscopy 43 3.5 Chromatography 43 3.6 General Method for the production of various novel C-2 substituted dimedones 44 3.7 Data of Synthesized Compounds 45 Chapter 4 56 RESULT AND DISCUSSION 56 4.1 1HNMR 59 4.2 13CNMR 59 REFERENCES 66 ix 1 Chapter 1 INTRODUCTION 1.1 Dimedone Dimedone (1) or Methone or 5,5-dimethyl-1,3-cyclohexanedione [1] is a highly reactive organic compound that is widely used in medicinal chemistry and organic synthesis. It is used as an active methylene compound as its most reactive centre i.e. C-2 is present between two strong electron withdrawing carbonyl groups. The C-2 of dimedone acts as a nucleophilic centre [2] while other less reactive sites i.e.C-1 and C-3 act as electrophilic centres. It is used in various organic reactions like knoevenagel condensation [3], Hantzsch reaction [4], Michael addition [3], Suzuki coupling [5] and Biginelli reaction [6] to form a number of useful products. It is also used as a precursor to form various biologically and pharmacologically active compounds that are used as anti-tumor [7], antibacterial [8], anti malarial [9], antifungal [10], antimicrobial [11] and antioxidant [12]. CH H3C 3 5 4 6 3 1 2 O O (1) 1.2 Physical properties of Dimedone The physical parameters of dimedone (1) are given in the table as under. Sr. No. Property State value 1 Molecular formula C8H12O2 [1] 2 Molecular mass 140.18[1] 3 Physical state Crystalline powder 4 Color Light yellow 5 Odor odorless 6 Decomposition point 147-150°C 7 Crystal structure Monoclinic[13] 2 1.3 Tautomeric forms of Dimedone In solution form, dimedone (1) exists in two tautomeric forms i.e. enol (2) and keto (1) in (1:2) ratio in chloroform [14]. O OH CH CH3 3 O O CH CH3 (1) 3 (2) 1.4 Hydrogen bonding Dimedone (1) in its crystalline form, exists in polymeric (3) forms of enol linked by hydrogen bonding [1]. H- - - - O O H3C CH3 H3C CH3 O- - - - O H (3) 1.5 Dimedone-Synthesis Dimedone (1) was prepared by the reaction of malonic ester (4) and mesityl oxide (5) [15]. ONa EtOOC CH3 O EtOOC EtOH COOEt + H C CH NaOEt 3 3 H3C O (4) (5) H3C O OH KOH H3C H C O HCl 3 OH CH3 CH3 (1) (Scheme 1) 3 An unpredicted formation of dimedone (1) was described by Henshall et al. [16] by the hydrolysis of 6-hydro-3-cyano-2-keto-4,4,6-trimethylpiperidine (6) in the presence of aqueous acetic acid and sulphuric acid. H3C CH3 H3C CH3 CN H2SO4(aq) COOH H3C -H2O H3C CH3COOH(aq) N O H3C COOH HO H O O (7) (6) (1) (Scheme 2) 1.6 Some important Reactions of Dimedone Dimedone is a well known organic molecule as it is an important part of almost every famous organic reaction and some of them are given as under. 1.6.1 Hantzsch reaction Wang et al. [4] has reported a synthetic strategy for polyhydroquinoline derivatives (9) by a simple multi component coupling reaction of dimedone (1), aldehydes and ethyl acetate (8) in the presence of ammonium acetate via Hantzsch mechanism. The reaction was aided by a small amount of Yb(OTf)3 (5 mol %) as a catalyst. The beneficial aspects of this strategy include eco friendly conditions, simple handling, normal temperature and high yield of the product. O O R O O Yb(OTf)3,5 mol 5% CO2Et 1eq. NH OAc H C 4 CH3 + H R + 3 O EtOH, r.t , 2-8 H, reflux H C N CH CH CO2Et 3 3 3 H3C H (1) (8) (9) (Scheme 3) 1.6.2 Tandem Aldol-Michael reactions Barakat et al. [17] has demonstrated a facile synthesis of some novel zwitter ion derivatives (12) by a one pot three components condensation reaction of dimedone (1), aldehydes (11) and various barbituric acid derivatives (10) using diethylamine under aqueous media via Tendem Aldol Michael mechanism. The charming aspects of this reaction were eco friendly conditions, less reaction time, high yield of the desired 4 product, simple workup, easy handling and affordable conditions. The structure of the synthesized compounds was verified by using various identification techniques such as, IR, NMR, Mass Spectroscopy, CHN, elemental analysis and X-ray diffraction. 1 R O H H3C O O O N O O H3C 1 1 R R H2O,NHEt2 N 1 + N N + R CH R.T,Reflux - + 3 HO O O NH2Et2 CH3 O O (1) (10) (11) (12) 2 R 2 R (Scheme 4) 1.6.3 Unsymmetrical Hantzsch reaction Davoodina et al. [18] has described an environmentally benign mechanism for the synthesis of polyhydroquinolines (14) via a multi component unsymmetrical Hantzsch reaction. The reaction underwent by condensing dimedone (1) with ammonium acetate, aldehydes and ethyl acetoacetate (13) in the presence of small amount of tet‐rabutylammonium hexatungstate [TBA]2[W6O19] as a catalyst in solvent free environment. The present protocol has been associated with plenty of benefits like, high activity and reusability of the catalyst and high yield of the product formed. O O R O O O CH3 [TBA]2[W6O19] OEt CH 3 R H + + NH4OAc O + EtO O Solvent free H3C N CH3 CH3 o 110 C H3C H (1) (13) (14) R= C6H5, 4-BrC6H4, 2-ClC6H4, 4-ClC6H4, 3-HOC6H4, 4-HOC6H4, 4-MeOC6H4, 4-MeC6H4 3-O2NC6H4 4-O2NC6H4 , 2-Furl, Et , n-Pr. (Scheme 5) 1.6.4 One-pot Knoevenagel and Michael addition reaction: Kantevari et al. [19] described a method for the production of 9-aryl-1,8- dioxooctahydroxanthene (15) derivatives and 2-aryl-methylene bis(3-hydroxy-2- cyclohexene-1-one) (16) derivatives through a Knoevenagel and Michael addition type 5 mechanism. The reaction proceeded by reacting dimedone (1) with various kinds of aldehydes under solvent free environment, aqueous media or using acetonitrile ,utilizing catalytic amounts of Silica supported perchloric acid ( HClO4–SiO2) and PPA–SiO2. O O O Ar O O Ar CH3 H O H3C CH Knoevenegal CH CH3 3+ ArCHO H C 3 O 3 O condensation Michael addition H3C OH CH (1) CH3 O 3 H3C HClO -SiO PPA-SiO2 4 2 O Ar O O Ar O O Ar O -H O 2 CH CH3 3 H3C H3C H3C O CH3 CH H3C CH3 O 3 H3C + H C OH OH (15) OH H CH3 3 (16) Ar = C6H5 , 4-ClC6H4 , 4-NMe2C6H4 , 3,4,5-(OMe)3C6H2, 4-OMe C6H4, 4-BrC6H4 , 3-OMe C6H4 , 4-NO2C6H4 , 2-NO2C6H4 , 4-OH C6H4, 3-Cl C6H4 , 2,4-Cl2C6H4 , 3-OH C6H4 , 4-CH3C6H4 (Scheme 6) 1.6.5 Biuret reaction Chassaing et al. [20] has described the formation of some unexpected products (18) by reacting different more or less active positions of dimedone (1) with benzofuroxan (17) in the presence of triethylamine. H CH3 CH3 OH O O N N O Et3N CH3 + O N O N CH 3 O CH3 H3C (1) (17) (18) (Scheme 7) 1.6.6 Begenilli reaction Chebanov et al. [6] presented a sonication assisted synthesis of some novel pyrazoloquinazolinone derivatives (20) by a Begenelli type coupling mechanism. The 6 reaction was done by refluxing dimedone (1) with various aromatic aldehydes and phenylpyrazol derivatives (19) for 30 minutes using ethanol as solvent. O N NH Ar O O N NH2 Sonication,EtOH N CH 3 H Ar + O + CH3 Reflux, 30 mins N CH3 H H C (1) (19) (20) 3 Ar = C6H5 , 4-MeC6H4 , 4-MeOC6H4, 4-BrC6H4, 4-NO2C6H4 , 2-MeOC6H4 (Scheme 8) 1.7 Importance of Dimedone Dimedone (1) is a valuable compound that has vast applications in biological and pharmaceutical field respectively and is used in a variety of purposes as under. 1.7.1 Pharmaceutical applications Dimedone (1) has been utilized in the preparation of substituted quinolines (21) [21] by a regioselective one pot two component method from formylated acetophenone and dimedone assisted by potassium bisulphate in aqueous media. Such type of compounds having quinoline groups show intense biological activities including anti asthmatic, anti infalammatory, anti hypertensiv and tyrosine kinase inhibiting agent.
Recommended publications
  • Reactions of Carbanions with Michael Acceptors and Electron-Deficient Arenes: Quantifying Polar Organic Reactivity

    Reactions of Carbanions with Michael Acceptors and Electron-Deficient Arenes: Quantifying Polar Organic Reactivity

    Dissertation zur Erlangung des Doktorgrades der Fakultät für Chemie und Pharmazie der Ludwig-Maximilians-Universität München Reactions of Carbanions with Michael Acceptors and Electron-deficient Arenes: Quantifying Polar Organic Reactivity Dipl. Chem. Florian Seeliger aus Hamburg 2008 Erklärung Diese Dissertation wurde im Sinne von § 13 Abs. 3 bzw. 4 der Promotionsordnung vom 29. Januar 1998 von Herrn Prof. Dr. Herbert Mayr betreut. Ehrenwörtliche Versicherung Diese Dissertation wurde selbständig und ohne unerlaubte Hilfe erarbeitet. München, 13.03.2008 ……..…………………………... Florian Seeliger Dissertation eingereicht am 13.03.2008 1.Gutachter Prof. Dr. Herbert Mayr 2.Gutachter Prof. Dr. Hendrik Zipse Mündliche Prüfung am 24.04.2008 Für Birgit Danksagung Ich möchte mich an dieser Stelle ganz herzlich bei Herrn Prof. Dr. Herbert Mayr für seine herausragende und beispielhafte Betreuung während der Durchführung meiner Arbeit, die interessante Themenstellung und seine stete Hilfs- und Diskussionsbereitschaft bedanken. Weiterhin gilt mein Dank Herrn Prof. Dr. Mieczyslaw Makosza, der es mir ermöglichte, für 2 Monate in Warschau zu forschen und Prof. Dr. Hendrik Zipse, der mir als Ratgeber für die quantenchemischen Rechnungen hilfreich zur Seite stand. Den Mitgliedern des Arbeitskreises danke ich für ein äußerst angenehmes Arbeitsklima mit vielen abwechslungsreichen Diskussionen über Chemie und andere Dinge. Meinen Laborkollegen Oliver Kaumanns, Heike Schaller, Markus Horn und Erik Breuer sei für ihre Hilfsbereitschaft und das tolle Arbeitsklima besonders
  • One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-Onesusing Zinc Ferrite Nanocatalyst and Its Bio Evaluation

    One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-Onesusing Zinc Ferrite Nanocatalyst and Its Bio Evaluation

    catalysts Article One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl-2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H-Quinazoline-5-OnesUsing Zinc Ferrite Nanocatalyst and Its Bio Evaluation Tentu Nageswara Rao 1 , Nalla Krishnarao 1, Faheem Ahmed 2,* , Suliman Yousef Alomar 3,*, Fadwa Albalawi 4, Panagal Mani 5, Abdullah Aljaafari 2 , Botsa Parvatamma 6, Nishat Arshi 7 and Shalendra Kumar 2,8 1 Department of Chemistry, Krishna University, Machilipatnam, Andhra Pradesh 521001, India; [email protected] (T.N.R.); [email protected] (N.K.) 2 Department of Physics, College of Science, King Faisal University, Hofuf, Al-Ahsa 31982, Saudi Arabia; [email protected] (A.A.); [email protected] (S.K.) 3 Doping Research Chair, Zoology Dept, College of Science, King Saud University, Riyadh 11451, Saudi Arabia 4 Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; [email protected] 5 Department of Biotechnology, Annai College of Arts&Science, Kumbakonam, Tamil Nadu 612503, India; [email protected] 6 Department of Organic Chemistry, GayathriP.G Courses, Gotlam, Vizianagaram 530045, India; [email protected] 7 Department of Basic Sciences, Preparatory Year Deanship, King Faisal University, Hofuf, Al-Ahsa 31982, Saudi Arabia; [email protected] Citation: Rao, T.N.; Krishnarao, N.; 8 Department of Physics, School of Engineering, University of Petroleum & Energy Studies, Ahmed, F.; Alomar, S.Y.; Albalawi, F.; Dehradun 248007, India Mani, P.; Aljaafari, A.; Parvatamma, * Correspondence: [email protected] (F.A.); [email protected] (S.Y.A.) B.; Arshi, N.; Kumar, S. One-Pot Synthesis of 7, 7-Dimethyl-4-Phenyl- Abstract: A simple and highly efficient protocol for the synthesis of derivatives 7, 7-dimethyl-4- 2-Thioxo-2,3,4,6,7, 8-Hexahydro-1H- phenyl-2-thioxo-2, 3, 4, 6, 7, 8-hexahydro-1H-quinazoline-5-one from 5, 5-dimethyl cyclohexane-1, Quinazoline-5-OnesUsing Zinc 3-dione (4a–4h) (dimedone) has been described.
  • A Mechanistic Investigation of the Reactions of Diselenides with Biological Oxidants

    A Mechanistic Investigation of the Reactions of Diselenides with Biological Oxidants

    A mechanistic investigation of the reactions of diselenides with biological oxidants Kelly Gardiner Faculty of Medicine (Sydney Medical School) The University of Sydney A thesis submitted to fulfil the requirements for the degree of Doctor of Philosophy 2019 Declaration This is to certify that, to the best of my knowledge, the content of this thesis is my own work. This thesis has not been submitted for any degree or other purpose. I certify that the intellectual content of this thesis is the product of my own work and that all the assistance received in preparing this thesis and sources have been acknowledged. Signed, Kelly Gardiner, BBiomedSc (Hons) ii Table of Contents Abstract ...................................................................................................................................ix Acknowledgements .................................................................................................................xi List of Abbreviations ............................................................................................................xii List of Figures ......................................................................................................................xvii List of Tables ........................................................................................................................xxv Publications Arising from this Thesis ..............................................................................xxvi 1. Introduction ........................................................................................................................1
  • Volumetric and Viscometric Study of Dimedone in Ethanol-Water Mixtures

    Volumetric and Viscometric Study of Dimedone in Ethanol-Water Mixtures

    Volumetric and Viscometric Study of Dimedone in Ethanol-Water Mixtures by Md. Jahangir Hossain ID No. 1553564 A thesis submitted in partial fulfilment of the requirements for the degree of M. Sc. in Department of Chemistry Khulna University of Engineering & Technology Khulna-9203, Bangladesh . ii Dedicated To My Beloved Parents iii Declaration This is to certify that the thesis work entitled "Volumetric and Viscometric Study of Dimedone in Ethanol-Water Mixtures" has been carried out by Md. Jahangir Hossain in the Department of Chemistry, Khulna University of Engineering & Technology, Khulna, Bangladesh. The above thesis work or any part of this work has not been submitted anywhere for the award of any degree or diploma. Signature of Supervisor Signature of Candidate iv v Acknowledgement All the admirations are for the Almighty Allah, Who helps me to accomplish my research works. I am extremely indebted to my respected supervisor Prof. Dr. Mohammad Abu Yousuf, Professor, Department of chemistry, Khulna University of Engineering and Technology, Khulna, for his careful guidance throughout the period of his dissertation. I would like to thank all my honorable teachers who give me mental support, advice and enthusiasm throughout my research. Without their cooperation, invaluable suggestion, encouragement and constructive guidance, throughout this research work would have not been materialized. I will remember their inspiring guidance and cordial behavior forever in my future life. I am pleased to express my gratitude to the Department Head Prof. Dr. Hasan Morshed for providing me necessary laboratory facilities and proper guidance for the research. I am highly grateful to the authority of KUET for giving the opportunity of research for the work.
  • Enantioselective Catalytic Transformations of Barbituric Acid Derivatives

    Enantioselective Catalytic Transformations of Barbituric Acid Derivatives

    catalysts Review Enantioselective Catalytic Transformations of Barbituric Acid Derivatives Claire Segovia, Arthur Lebrêne , Vincent Levacher , Sylvain Oudeyer and Jean-François Brière * Normandie University, UNIROUEN, INSA Rouen, CNRS, COBRA, 76000 Rouen, France; [email protected] (C.S.); [email protected] (A.L.); [email protected] (V.L.); [email protected] (S.O.) * Correspondence: [email protected]; Tel.: +33-235-522-464 Received: 20 December 2018; Accepted: 15 January 2019; Published: 1 February 2019 Abstract: Since the beginning of the 20th century, numerous research efforts made elegant use of barbituric acid derivatives as building blocks for the elaboration of more complex and useful molecules in the field of pharmaceutical chemistry and material sciences. However, the construction of chiral scaffolds by the catalytic enantioselective transformation of barbituric acid and derivatives has only emerged recently. The specific properties of these rather planar scaffolds, which also encompass either a high Brønsted acidity concerning the native barbituric acid or the marked electrophilic character of alkylidene barbituric acids, required specific developments to achieve efficient asymmetric processes. This review covers the enantioselective catalytic reactions developed for barbituric acid platforms using an organocatalytic and metal-based enantioselective sequences. These achievements currently allow several unique addition and annulation reactions towards the construction of high valued chiral heterocycles from barbituric acid derivatives along with innovative enantioselective developments. Keywords: organocatalysis; asymmetric synthesis; barbituric acid; alkylidene barbituric acid; metal based-catalysis; cycloaddition; annulation reaction 1. Introduction 1.1. Context Barbituric acid 1, namely 2,4,6-(lH,3H,5H)-pyrimidinetrione, and derivatives are fascinating building blocks in organic synthesis (Figure1).
  • Investigation of Mechanochemical Synthesis of Condensed 1,4-Diazines and Pharmaceutically Attractive Hydrazones Paulo Filho Marques De Oliveira

    Investigation of Mechanochemical Synthesis of Condensed 1,4-Diazines and Pharmaceutically Attractive Hydrazones Paulo Filho Marques De Oliveira

    Investigation of mechanochemical synthesis of condensed 1,4-diazines and pharmaceutically attractive hydrazones Paulo Filho Marques de Oliveira To cite this version: Paulo Filho Marques de Oliveira. Investigation of mechanochemical synthesis of condensed 1,4-diazines and pharmaceutically attractive hydrazones. Chemical and Process Engineering. Ecole des Mines d’Albi-Carmaux, 2015. English. NNT : 2015EMAC0007. tel-01271090 HAL Id: tel-01271090 https://tel.archives-ouvertes.fr/tel-01271090 Submitted on 8 Feb 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 5)µ4& &OWVFEFMPCUFOUJPOEV %0$503"5%&-6/*7&34*5²%&506-064& %ÏMJWSÏQBS École Nationale Supérieure des Mines d'Albi-Carmaux conjointement avec l'INP Toulouse 1SÏTFOUÏFFUTPVUFOVFQBS Paulo Filho MARQUES de OLIVEIRA le vendredi 30 octobre 2015 5JUSF Investigation of mechanochemical synthesis of condensed 1,4-diazines and pharmaceutically attractive hydrazones ²DPMFEPDUPSBMF et discipline ou spécialité ED MEGEP : Génie des procédés et de l'Environnement 6OJUÏEFSFDIFSDIF Centre RAPSODEE, CNRS UMR 5302
  • A Concise Study on Dimedone: a Versatile Molecule in Multi-Component Reac- Tions, an Outlook to the Green Reaction Media

    A Concise Study on Dimedone: a Versatile Molecule in Multi-Component Reac- Tions, an Outlook to the Green Reaction Media

    Accepted Manuscript Original article A concise study on dimedone: a versatile molecule in multi-component reac- tions, an outlook to the green reaction media Kobra Nikoofar, Fatemeh Molaei Yielzoleh PII: S1319-6103(17)30144-8 DOI: https://doi.org/10.1016/j.jscs.2017.12.005 Reference: JSCS 930 To appear in: Journal of Saudi Chemical Society Received Date: 25 October 2017 Revised Date: 7 December 2017 Accepted Date: 11 December 2017 Please cite this article as: K. Nikoofar, F.M. Yielzoleh, A concise study on dimedone: a versatile molecule in multi- component reactions, an outlook to the green reaction media, Journal of Saudi Chemical Society (2017), doi: https:// doi.org/10.1016/j.jscs.2017.12.005 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A concise study on dimedone: a versatile molecule in multi-component reactions, an outlook to the green reaction media Kobra Nikoofar*, Fatemeh Molaei Yielzoleh Department of Chemistry, Faculty of Physics and Chemistry, Alzahra University, Vanak, P.O. Box 1993893973, Tehran, Iran. * E-mail: [email protected], [email protected] Tel/fax: +98 2188041344 Abstract: Dimedone is an interesting and versatile motif in most organic transformations.