DOCSLIB.ORG

New Chemistry of N´-Arylbenzamidines

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
New Chemistry of N´-Arylbenzamidines DEPARTMENT OF CHEMISTRY NEW CHEMISTRY OF N΄-ARYLBENZAMIDINES Mirallai DOCTOR OF PHILOSOPHY DISSERTATION I. STYLIANA IOANNIS MIRALLAI Styliana 2015 Mirallai I. Styliana DEPARTMENT OF CHEMISTRY NEW CHEMISTRY OF N΄-ARYLBENZAMIDINES STYLIANA IOANNIS MIRALLAIMirallai I. A Dissertation Submitted to the University of Cyprus in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy Styliana AUGUST 2015 Mirallai I. Styliana © Styliana Ioannis Mirallai, 2015 VALIDATION PAGE Doctoral Candidate: Styliana Ioannis Mirallai Doctoral Thesis Title: New Chemistry of N΄-Arylbenzamidines The present Doctoral Dissertation was submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at the Department of Chemistry and was approved on the ………………. by the members of the Examination Committee. Examination Committee: 1. Dr. Panayiotis A. Koutentis, University of Cyprus (Research Supervisor) Mirallai…………..…………….. 2. Prof. Rainer Beckert, Friedrich-SchillerI. University of Jena (External Examiner) …………..…………….. 3. Dr. Fawaz Aldabbagh, National University of Ireland, Galway (External Examiner) …………..…………….. 4. Dr. Athanassios Nicolaides, University of Cyprus (Internal Examiner) Styliana …………..…………….. 5. Dr. Nikos Chronakis, University of Cyprus (Committee Chairman) …………..…………….. i Mirallai I. Styliana ii EXPERIMENTAL PROCESSES ACCOMPLISHMENT STATEMENT The present doctoral dissertation was submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy of the University of Cyprus. The work described within this thesis has been carried out exclusively by Styliana I. Mirallai at the Organic Chemistry Research Laboratory, Department of Chemistry, University of Cyprus under the supervision of Dr. Panayiotis A. Koutentis (September 2009-June 2015). The exceptions include: the elemental analysis of all compounds performed by Stephen Boyer at London Metropolitan University and the single crystal X-ray crystallography studies performed by Dr. Maria Manoli and Dr. Manolis J. Manos. Mirallai I. Date ………………………. Name/Signature …………………………………………. Styliana iii Mirallai I. Styliana iv “Always choose the hard way” Mirallai I. Styliana v Mirallai I. Styliana vi ΠΕΡΙΛΗΨΗ Η παρούσα διδακτορική διατριβή αρχίζει με μια σύντομη εισαγωγή (Κεφάλαιο 1) στην ετεροκυκλική χημεία, η οποία στη συνέχεια επικεντρώνεται στο άζωτο ως ετεροάτομο σε αρωματικά συστήματα, καθώς επίσης και στην χρήση των αμιδινών ως πρόδρομα μόρια για τη σύνθεση ιμιδαζολών και πυριμιδινών. Στο Κεφάλαιο 2, γίνεται αρχικά διερεύνηση της κλασικής σύνθεσης των N'- αρυλοβενζαμιδινών 126, χρησιμοποιώντας ως πρόδρομα μόρια ανιλίνες και βενζονιτρίλια υπό την παρουσία του AlCl3. Ακολούθως, παρουσιάζεται μια βελτιωμένη σύνθεση των N'-αρυλοβενζαμιδινών 126, η οποία απαιτεί τον σχηματισμό του συμπλόκου βενζονιτρίλιο-AlCl3 πριν από την προσθήκη της ανιλίνης. Έχοντας συνθέσει μια μικρή βιβλιοθήκη από 2-αμινοφαινυλο-N'-αρυλοβενζαμιδίνες 75 διερευνήσαμε την αντίδρασή τους με τα ηλεκτρονιόφιλα 4,5-διχλωρο-1,2,3-διθειαζολικό χλωρίδιο (74) (Appel salt) και τετρακυανοαιθένιο (TCNE): Η επεξεργασία των 2- αμινοφαινυλο-N'-αρυλοβενζαμιδινών 75 με το Appel salt 74 έδωσε τα καινούρια 3-αρυλ- 4-ιμινο-3,4-διυδροκιναζολινο-2-καρβονιτρίλια 103Mirallai (Κεφάλαιο 3). Αντιθέτως, η επεξεργασία των 2-αμινοφαινυλ-N'-αρυλβενζαμιδινών 75 με το TCNE αναφέρεται ότι, οδηγεί στον σχηματισμό των ισομερών 4-αρυλoκιναζολινο-2-καρβονιτριλίων 76. Στο Κεφάλαιο 4 παρουσιάζεται η επαναδιερεύνI.ηση της αντίδρασης η οποία οδήγησε στην εύρεση τριών διαφορετικών συνθηκών οι οποίες δίνουν ως κύρια προϊόντα τα [4H- ιμιδαζολο-4-υλιδενο]μαλονονιτρίλια 106, τα 4-αρυλoκιναζολινο-2-καρβονιτρίλια 76 ή τις ιμινοκιναζολίνες 103, αντίστοιχα. Στο Κεφάλαιο 5, η προαναφερθείσα αντίδραση με το TCNE απλουστεύθηκε για την αποφυγή του σχηματισμού των κιναζολινών 76 ή 103. Επομένως, η αντικατάσταση των 2- αμινοφαινυλο-N'-αρυλοβενζαμιδινών 75 με τις N'-αρυλοβενζαμιδίνες 126 οδήγησε στον σχηματισμό των (1,2,2-τρικυανοβινυλο)βενζαμιδινών 156 σε καλές αποδόσεις, οι οποίες μπορούνStyliana να υποστούν κυκλοποίηση 5 -exo-dig και να αποδόσουν τα ισομερή [1H- ιμιδαζολο-4(5H)-υλιδενο]μαλονονιτρίλια 157 σε ψηλές αποδόσεις. Τα μαλονονιτρίλια 157 με τη σειρά τους μπορούν να υποστούν αναδιάταξη Dimroth για να δώσουν τα [1H- ιμιδαζολο-5(4H)-υλιδενο]μαλονονιτρίλια 158 σε ψηλές αποδόσεις, ενώ η θερμόλυση των μαλονονιτριλίων 158 οδηγεί στον σχηματισμό των 2-φαινυλο-3H-ιμιδαζολο[4,5- vii Mirallai I. Styliana viii b]κινολινο-9-καρβονιτριλίων 159. Στο Κεφάλαιο 6, παρουσιάζεται η επεξεργασία των άμεσα διαθέσιμων κιναζολιμινών και 4-ανιλινοκιναζολινών με μια πληθώρα από καταλύτες Pd και Cu η οποία δίνει πρόσβαση, μέσω οξειδωτικών και μη οξειδωτικών συζεύξεων, στα βενζο[4,5]ιμιδαζο[1,2-c]κιναζολινο-6-καρβονιτρίλια 215 σε ψηλές αποδόσεις. Η διδακτορική διατριβή ολοκληρώνεται με την παρουσίαση των πειραματικών διαδικασιών και της βιβλιογραφίας. Mirallai I. Styliana ix Mirallai I. Styliana x ABSTRACT The Thesis begins with a brief introduction (Chapter 1) on heterocyclic chemistry, which then focuses on nitrogen heteroaromatics and the use of amidines in the synthesis of imidazoles and pyrimidines. In Chapter 2, the classical synthesis of N'-arylbenzamidines 126, starting from anilines and benzonitriles in the presence of AlCl3, is reinvestigated. Herein, an improved synthesis of N'-arylbenzamidines 126 is presented, that involves preforming the AlCl3 complex of benzonitrile prior to the addition of the aniline. Having in hand a small library of 2-aminophenyl-N'-arylbenzamidines 75 their reaction with electrophiles, 4,5-dichloro-1,2,3-dithiazolium chloride (74) (Appel salt) and tetracyanoethene (TCNE) was investigated: The treatment of 2-aminophenyl-N'-aryl- benzamidines 75 with Appel salt 74 gave novel 3-aryl-4-imino-3,4-dihydroquinazoline-2- carbonitriles 103 (Chapter 3). In contrast, treatment of 2-aminophenyl-N-arylbenzamidines 75 with TCNE was reported to afford the isomeric 4-arylquinazoline-2-carbonitriles 76. In Chapter 4 a reinvestigation of this reaction leads toMirallai three sets of conditions that give as major products the [4H-imidazol-4-ylidene]malononitriles 106, the 4-arylquinazoline-2- carbonitriles 76 or the iminoquinazolines 103I., respectively. In Chapter 5, the latter reaction with TCNE was simplified to avoid the formation of either quinazolines 76 or 103. As such, by replacing 2-amino-N'-arylbenzamidines 75 with N'- arylbenzamidines 126 a series of (1,2,2-tricyanovinyl)benzamidines 156 prepared in good yields that can undergo a 5-exo-dig cyclization to yield the isomer [1H-imidazol-4(5H)- ylidene]malononitriles 157 in high yields. These can then Dimroth rearrange to give the [1H-imidazol-5(4H)-ylidene]malononitriles 158 in high yields, thermolysis of which formed the 2-phenyl-3H-imidazo[4,5-b]quinoline-9-carbonitriles 159. In Chapter 6, treatment of the readily available quinazolinimines and 4- anilinoquinazolinesStyliana with a variety of Pd and Cu catalysts gave access, via oxidative and non oxidative coupling routes, to the biologically important benzo[4,5]imidazo[1,2- c]quinazoline-6-carbonitriles 215 in variable yields. The Thesis finishes with a detailed Experimental section and a References section. xi Mirallai I. Styliana xii ACKNOWLEDGEMENTS The years spent on my PhD were the most valuable and fruitful journey of my life. However, I could not travel and accomplish this journey without the tremendous support of my PhD supervisor, Dr. P. A. Koutentis. Thus, I thank him for providing me the opportunity to work on the projects described herein, for the knowledge I gained and for his help and support all these years. I thank the Cyprus Research Promotion Foundation (CRPF) (Grant No ΕΠΙΧΕΙΡΗΣΕΙΣ/ΕΦΑΡΜ/0308/19 and NΕΑ ΥΠΟΔΟΜΗ/ΝΕΚΥΠ/0308/02) and University of Cyprus (YPOTROFIES UCY/09-2013 - 09-2014) for financial support. I thank the A. G. Leventis Foundation and the CRPF (Grant No. NΕΑ ΥΠΟΔΟΜΗ/ΝΕΚΥΠ/0308/02) respectively, for helping establish the 300 MHz and the 500 MHz NMR facilities in the University of Cyprus. I also thank Stephen Boyer for elemental analysis (London Metropolitan University) and the laboratory technicians Savvas Savva and Panicos Andreou for their technical support (University of Cyprus). Within the team I thank Andreas Kalogirou, Maria KoyioniMirallai and Georgia Zissimou for their friendship, encouragement, support and knowledge exchange all these years. I would also like to thank a former member of the team, Hearklidia Ioannidou, for her friendship and support. I. Finally, I would like to thank my family for their love, patience and support through the years of my PhD. Styliana xiii Mirallai I. Styliana xiv CONTENTS Sections Page Abstract in Greek vii Abstract in English xi Acknowledgements xiii Contents xv Abbreviations xix Brief Contents Chapter 1. Introduction 1 Chapter 2. Reinvestigating the synthesis of N-arylbenzamidines from benzonitriles and anilines in the presence of AlCl3 24 Chapter 3. The one-step conversion of 2-amino-N'-arylbenzamidines into 3-aryl-4-imino-3,4-dihydroquinazoline-2-carbonitrilesMirallai using 4,5-dichloro-1,2,3-dithiazolium chloride I. 31 Chapter 4. The reaction of 2-amino-N'-arylbenzamidines with tetracyanoethylene reinvestigated: Routes to imidazoles, quinazolines and quinolino[2',3':4,5]imidazo[1,2-c]quinazoline-8-carbonitrile 41 Chapter 5. Reactions of tetracyanoethylene with N'-arylbenzamidines: A short route to 2-phenyl-3H-imidazo[4,5-b]quinoline-9-carbonitriles 61 Chapter 6. The conversion of 4-anilinoquinazoline- and 3-aryl-4-imino-
Load more

Recommended publications
  • MO STUDIES of SOME NONBENZENOID AROMATIC SYSTEMS Electrons
    MO STUDIESOFSOME NONBENZENOID AROMATIC SYSTEMS MIcL J. S. DEWAR Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, USA ABSTRACT A new version of(MINDO/3) of the MINDO semiempirical SCF MO method has been developed which seems to avoid the serious defects of earlier treat- ments. Very extensive tests show that it gives results at least comparable with those of the best ab initio SCF procedures at one-hundred-thousandth of the cost. Calculations are reported for the benzynes, for various cyclic polymethines, including (CH), (CH)3, (CH), (CH)4, (CH), (CH)5, (CH), (CI{), and (CH)18, for azulene and pentalene, for the cycloheptatriene—norcaradiene equilibrium, for spironoatetraene, for silabenzene, for a variety of poly- azines and polyazoles, and for various aromatic and potentially aromatic sulphur-containing compounds. INTRODUCTION While theoretical organic chemistry has long been based on the results of quantum mechanical treatments, in particular simplified versions of the molecular orbital (MO) method, these until recently have been too inaccurate to give results of more than qualitative significance. Many problems have therefore remained outside the scope of current theory since their solution depended on quantitative estimates of the relative energies of atoms and molecules. Recently it has become possible to carry out such quantitative calculations and the results are already proving of major chemical interest in a number of areas. The purpose of this lecture is to report some preliminary studies of this kind of various aromatic systems and problems connected with them. There is of course no question of obtaining accurate solutions of the Schrodinger equation for molecules large enough to be of chemical interest.
    [Show full text]
  • Non-Empirical Calculations on the Electronic Structure of Olefins and Aromatics
    NON-EMPIRICAL CALCULATIONS ON THE ELECTRONIC STRUCTURE OF OLEFINS AND AROMATICS by Robert H. Findlay, B.Sc. Thesis presented for the Degree of Doctor of philosophy University of Edinburgh December 1973 U N /),, cb CIV 3 ACKNOWLEDGEMENTS I Wish to express my gratitude to Dr. M.H. Palmer for his advice and encouragement during this period of study. I should also like to thank Professor J.I.G. Cadogan and Professor N. Campbell for the provision of facilities, and the Carnegie Institute for the Universities of Scotland for a Research Scholarship. SUMMARY Non-empirical, self-consistent field, molecular orbital calculations, with the atomic orbitals represented by linear combinations of Gaussian-type functions have been carried out on the ground state electronic structures of some nitrogen-, oxygen-, sulphur- and phosphorus-containing heterocycles. Some olefins and olefin derivatives have also been studied. Calculated values of properties have been compared with the appropriate experimental quantities, and in most cases the agreement is good, with linear relationships being established; these are found to have very small standard deviations. Extensions to molecules for which there is no experimental data have been made. In many cases it has been iôtrnd possible to relate the molecular orbitals to the simplest member of a series, or to the hydrocarbon analogue. Predictions of the preferred geometry of selected molecules have been made; these have been used to predict inversion barriers and reaction mechanisms. / / The extent of d-orbital participation in molecules containing second row atoms has been investigated and found to be of trivial importance except in molecules containing high valence states of the second row atoms.
    [Show full text]
  • Stabilization of Hexazine Rings in Potassium Polynitride at High Pressure
    Stabilization of hexazine rings in potassium polynitride at high pressure Yu Wang1, Maxim Bykov2,3, Elena Bykova2, Xiao Zhang1, Shu-qing Jiang1, Eran Greenberg4, Stella Chariton4, Vitali B. Prakapenka4, Alexander F. Goncharov1,2, 1 Key Laboratory of Materials Physics, Institute of Solid State Physics, Chinese Academy of Sciences, Hefei 230031, Anhui, People’s Republic of China 2 Earth and Planets Laboratory, Carnegie Institution of Washington, 5251 Broad Branch Road NW, Washington, DC 20015, USA 3 Department of Mathematics, Howard University, Washington, DC 20059, USA 4 Center for Advanced Radiations Sources, University of Chicago, Chicago, Illinois 60637, USA Correspondence should be addressed to: [email protected] 1 Polynitrogen molecules represent the ultimate high energy-density materials as they have a huge potential chemical energy originating from their high enthalpy. However, synthesis and storage of such compounds remain a big challenge because of difficulties to find energy efficient synthetic routes and stabilization mechanisms. Compounds of metals with nitrogen represent promising candidates for realization of energetic polynitrogen compounds, which are also environmentally benign. Here we report the synthesis of polynitrogen planar N6 hexazine rings, stabilized in K2N6 compound, which was formed from K azide upon laser heating in a diamond anvil cell at high pressures in excess of 45 GPa and remains metastable down to 20 GPa. Synchrotron X-ray diffraction and Raman spectroscopy are used to identify this material, also exhibiting metallic luster, being all consistent with theoretically predicted structural, vibrational and electronic properties. The documented here N6 hexazine rings represent new highly energetic polynitrogens, which have a potential for future recovery and utilization.
    [Show full text]
  • Heterocyclic Chemistry at a Glance Other Titles Available in the Chemistry at a Glance Series
    Heterocyclic Chemistry at a Glance Other Titles Available in the Chemistry at a Glance series: Steroid Chemistry at a Glance Daniel Lednicer ISBN: 978-0-470-66084-3 Chemical Thermodynamics at a Glance H. Donald Brooke Jenkins ISBN: 978-1-4051-3997-7 Environmental Chemistry at a Glance Ian Pulford, Hugh Flowers ISBN: 978-1-4051-3532-0 Natural Product Chemistry at a Glance Stephen P. Stanforth ISBN: 978-1-4051-4562-6 The Periodic Table at a Glance Mike Beckett, Andy Platt ISBN: 978-1-4051-3299-2 Chemical Calculations at a Glance Paul Yates ISBN: 978-1-4051-1871-2 Organic Chemistry at a Glance Laurence M. Harwood, John E. McKendrick, Roger Whitehead ISBN: 978-0-86542-782-2 Stereochemistry at a Glance Jason Eames, Josephine M Peach ISBN: 978-0-632-05375-9 Reaction Mechanisms at a Glance: A Stepwise Approach to Problem-Solving in Organic Chemistry Mark G. Moloney ISBN: 978-0-632-05002-4 Heterocyclic Chemistry at a Glance Second Edition JOHN A. JOULE The School of Chemistry, The University of Manchester, UK KEITH MILLS Independent Consultant, UK This edition fi rst published 2013 © 2013 John Wiley & Sons, Ltd Registered offi ce John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom For details of our global editorial offi ces, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com. The right of the author to be identifi ed as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988.
    [Show full text]
  • Interactions and Positive Electrostatic Potentials of N-Heterocycles Arise from the Cite This: Chem
    ChemComm View Article Online COMMUNICATION View Journal | View Issue Anion–p interactions and positive electrostatic potentials of N-heterocycles arise from the Cite this: Chem. Commun., 2014, 50, 11118 positions of the nuclei, not changes in the Received 9th July 2014, p-electron distribution† Accepted 5th August 2014 DOI: 10.1039/c4cc05304d Steven E. Wheeler* and Jacob W. G. Bloom www.rsc.org/chemcomm We show that the positive electrostatic potentials and molecular the molecule. As a result, a positive Qzz value can indicate the quadrupole moments characteristic of p-acidic azines, which depletion of electron density above the ring centre (e.g., underlie the ability of these rings to bind anions above their centres, reduction of the p-electron density) or the movement of nuclear arise from the position of nuclear charges, not changes in the charge towards the ring centre. Similarly, a positive ESP above p-electron density distribution. an aromatic ring can arise from changes in either the electronic or nuclear charge distributions.7 These distinctions are rarely Anion–p interactions1 are attractive non-covalent interactions made in discussions of anion–p interactions,1,2 which focus between anions and the faces of p-acidic rings.2 They often almost exclusively on the concepts of p-acidity and p-electron- involve azabenzenes (azines) such as s-triazine and s-tetrazine, deficiency. and have emerged as powerful tools for anion binding, recogni- Previously, Wheeler and Houk showed8 that substituent- tion and transport, and even catalysis.3 Despite rapidly-growing induced changes in the ESPs of substituted arenes are domi- interest in these non-covalent interactions, there is a dearth of nated by through-space effects, not changes in the p-electron rigorous explanations of their origin.4 Most authors2g,h ascribe density.
    [Show full text]
  • 10 Heterocycles and Supramolecular Chemistry
    Heterocycles in Life and Society Heterocycles in Life and Society: An Introduction to H eterocyclic Chemistry, Biochemistry and Applications , Second Edition. Alexander F . P ozhars kii, Anatoly T. S oldatenkov and A lan R . K atritzky. © 2011 John Wiley & Sons, Ltd. Published 2011 by John Wiley & Sons, Ltd. ISBN: 978-0-470-71411-9 Heterocycles in Life and Society An Introduction to Heterocyclic Chemistry, Biochemistry and Applications Second Edition by ALEXANDER F. POZHARSKII Soros Professor of Chemistry, Southern Federal University, Russia ANATOLY T. SOLDATENKOV Professor of Chemistry, Russian People’s Friendship University, Russia ALAN R. KATRITZKY Kenan Professor of Chemistry, University of Florida, Gainesville, USA A John Wiley & Sons, Ltd., Publication This edition first published 2011 c 2011 John Wiley & Sons, Ltd Registered office John Wiley & Sons Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, United Kingdom For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com. The right of the author to be identified as the author of this work has been asserted in accordance with the Copyright, Designs and Patents Act 1988. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher. Wiley also publishes its books in a variety of electronic formats.
    [Show full text]
  • Hypervalence and Aromaticity
    VRIJE UNIVERSITEIT Hypervalence and Aromaticity ACADEMISCH PROEFSCHRIFT ter verkrijging van de graad Doctor aan de Vrije Universiteit Amsterdam, op gezag van de rector magnificus prof.dr. L.M. Bouter, in het openbaar te verdedigen ten overstaan van de promotiecommissie van de faculteit der Exacte Wetenschappen op maandag 2 juni 2008 om 10.45 uur in de aula van de universiteit, De Boelelaan 1105 door Simon Christian André Henri Pierrefixe geboren te Vannes, Frankrijk promotor: prof.dr. E. J. Baerends copromotor: dr. F. M. Bickelhaupt Hypervalence & Aromaticity Simon C. A. H. PIERREFIXE Cover designed by wrinkly pea: www.wrinklypea.com ISBN: 978-90-8891-0432 Contents 1 General Introduction 1 1.1 Hypervalence 2 1.2 Aromaticity 3 2 Theory and Methods 7 2.1 The Schrödinger equation 7 2.2 Electronic-structure calculations 8 2.3 Density functional theory 9 2.4 Kohn-Sham Molecular Orbital model 10 Part I HYPERVALENCE 13 – – – – 3 Hypervalence and the Delocalizing versus Localizing Propensities of H3 , Li3 , CH5 and SiH5 15 3.1 Introduction 16 3.2 Theoretical Methods 18 3.3 Results and Discussions 19 3.4 Conclusions 25 4 Hypervalent Silicon versus Carbon: Ball-in-a-Box Model 27 4.1 Introduction 28 4.2 Theoretical Methods 31 4.3 Results and Discussions 31 4.4 Conclusions 44 ii 5 Hypervalent versus Nonhypervalent Carbon in Noble-Gas Complexes 47 5.1 Introduction 48 5.2 Theoretical Methods 49 5.3 Results and Discussions 51 5.4 Conclusions 64 Part II AROMATICITY 67 6 Aromaticity. Molecular Orbital Picture of an Intuitive Concept 69 6.1 Introduction
    [Show full text]
  • PDF Document
    Acta Chim. Slov. 2011, 58, 509–520 509 Scientific paper Protonation of Azines and Purines as a Model for the Electrophilic Aromatic Substitution – Rationalization by Triadic Formula Robert Vianello1,2 1 National Institute of Chemistry, Hajdrihova 19, SI–1000 Ljubljana, Slovenia. 2 Ru|er Bo{kovi} Institute, Bijeni~ka cesta 54, HR–10000 Zagreb, Croatia * Corresponding author: E-mail: [email protected] Received: 06-05-2011 Dedicated to Professor Du{an Had`i on the occasion of his 90th birthday Abstract First gas-phase carbon proton affinities of eleven azines and purines (pyrrole, pyrazole, imidazole, pyridine, pyridazine, pyrimidine, pyrazine, bicyclic purine, pyridine–N–oxide, 2-aminopyrimidine and uracil) were calculated by a composi- te G3B3 methodology and used to probe their susceptibility to undergo electrophilic aromatic substitution (EAS), ta- king benzene as a reference molecule. The results revealed excellent agreement with the available experimental data and were interpreted using the triadic approach. We found out that pyrroles, which are more reactive towards EAS reaction than benzene, are stronger carbon bases than the latter compound, whereas pyridines exhibit lower carbon basicity, be- ing at the same time less reactive toward substitution by electrophiles than benzene. In all of the investigated molecules the frontier orbital describing the corresponding π–electron density at the carbon atom to be protonated is HOMO as calculated by the HF/G3large//B3LYP/6–31G(d) level of theory. Our results are in a disagreement with the work by D’Auria (M. D’Auria, Tetrahedron Lett. 2005, 46, 6333–6336; Lett. Org. Chem. 2005, 2, 659–661), who at B3LYP/6–311+G(d,p) level found out that in some of systems investigated here the HOMO orbital is not of π–symme- try, which was used to rationalize the lower reactivity of these systems towards EAS.
    [Show full text]
  • Review in Heterocyclic Compounds 51
    Journal of Plastic and Polymer Technology (JPPT) Vol. 1, Issue 1, Jun 2015, 49-64 © TJPRC Pvt. Ltd. REVIEW PAPER IN HETEROCYCLIC COMPOUNDS NAGHAM MAHMOOD ALJAMALI Organic Chemistry, Chemistry Department, College of Education ABSTRACT In this review paper, information about heterocyclic compounds, methods of synthesis, reactions , properties , stability, saturated and unsaturated cycles , aliphatic and aromatic cycles have been thoroughly reviewed and discussed. KEYWORDS : Heterocyclic, Three Membered, Seven, Cyclization, Sulfur,Nitrogen INTRODUCTION Three Membered Rings Heterocycles with three atoms in the ring are more reactive because of ring strain. Those containing one heteroatom are, in general, stable. Those with two heteroatoms are more likely to occur as reactive intermediates. Table 1: Common 3-Membered Heterocycles with One Heteroatom Are Heteroatom Saturated Unsaturated Nitrogen Aziridine Azirine Oxygen Oxirane (ethylene oxide, epoxides) Oxirene Sulfur Thiirane (episulfides) Thiirene Tabli 2: Those with Two Heteroatoms Include Heteroatom Saturated Unsaturated Nitrogen Diazirine Nitrogen/oxygen Oxaziridine Oxygen Dioxirane MEMBERED RINGS Table 3: Compounds with One Heteroatom Heteroatom Saturated Unsaturated Nitrogen Azetidine Azete Oxygen Oxetane Oxete Sulfur Thietane Thiete Table 4: Compounds with Two Heteroatoms Heteroatom Saturated Unsaturated Nitrogen Diazetidine Oxygen Dioxetane Dioxete Sulfur Dithietane Dithiete www.tjprc.org [email protected] 50 Nagham Mahmood Aljamali MEMBERED RINGS With heterocycles containing five
    [Show full text]
  • Quantifying Non-Covalent Interactions in Biological Systems
    QUANTIFYING NON-COVALENT INTERACTIONS IN BIOLOGICAL SYSTEMS THROUGH COMPUTATIONAL CHEMISTRY A Dissertation by YI AN Submitted to the Office of Graduate and Professional Studies of Texas A&M University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Chair of Committee, Steven E. Wheeler Committee Members, Robert R. Lucchese Christian Hilty Wonmuk Hwang Head of Department, Francois P. Gabbai December 2015 Major Subject: Chemistry Copyright 2015 Yi An ABSTRACT Non-covalent interactions, especially those involving arenes, perform critical roles in biological processes, including ligand-protein and ligand-nucleic acid interactions, as well as protein and DNA/RNA stability and function. We investigated non-covalent interactions involving aromatic rings using computational chemistry in four contexts: sequence-selective DNA-binding antibodies, nitroarene-protein interactions, heterocycle-adenine interactions, and the tuning of amino acid pKa’s. We first surveyed recent advances in our understanding of alkali metal cation-π interactions and their role in both experimental and theoretical fields. Then quantum mechanical computations and classical molecular mechanics based molecular dynamics simulations were utilized as the main tools to explore non-covalent interactions involving π-system in biological systems. We present computational analyses of the binding of four dinucleotides to a sequence-selective single-stranded DNA (ssDNA) binding antibody (ED-10) and selected point-mutants using MMGBSA as well as DFT applied to a cluster model of the binding site. The results indicate that the sequence selectivity arises primarily from differences in the strength of π-stacking and XH/π interactions with the surrounding aromatic residues; hydrogen bonds play little role.
    [Show full text]
  • SUPPLEMENTARY INFORMATION Relating Nucleus Independent Chemical Shifts with Integrated Current Density Strengths†
    Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is © the Owner Societies 2021 SUPPLEMENTARY INFORMATION Relating nucleus independent chemical shifts with integrated current density strengths† Slavko Radenković* and Slađana Đorđević University of Kragujevac, Faculty of Science, P. O. Box 60, 34000 Kragujevac, Serbia *Corresponding authors: [email protected] S1 a) b) Fig. S1 Integrated bond current strengths in 1,2,4-triazine (a) and 2,4-diazafuran (b). 퐽total values are given in black, 퐽휋 in blue, and 퐽휎 in red. S2 Table S1 Calculated NICSiso aromaticity indices for different hights above the ring plane of the studied molecules. molecule NICSiso(0) NICSiso(0.25) NICSiso(0.5) NICSiso(0.75) NICSiso(1) NICSiso(1.25) NICSiso(1.5) NICSiso(1.75) benzene -8.13 -8.76 -9.94 -10.49 -10.01 -8.84 -7.43 -6.07 pyridine -6.81 -7.67 -9.33 -10.28 -9.99 -8.86 -7.43 -6.04 1,2-diazine -5.52 -6.26 -8.63 -10.17 -9.77 -9.17 -7.72 -5.88 1,3-diazine -5.20 -6.59 -8.65 -9.91 -10.06 -8.68 -7.26 -6.16 1,4-diazine -5.07 -6.35 -8.62 -10.08 -10.20 -9.02 -7.58 -6.28 1,2,3-triazine -4.03 -5.30 -8.20 -10.15 -9.34 -9.35 -7.87 -5.56 1,2,4-triazine -3.35 -4.82 -7.75 -9.77 -10.04 -9.09 -7.67 -6.23 1,3,5-triazine -3.84 -5.30 -7.80 -9.36 -10.35 -8.29 -6.90 -6.38 1,2,3,4-tetrazine -1.89 -3.75 -7.30 -9.81 -9.87 -9.42 -7.95 -6.09 1,2,3,5-tetrazine -1.29 -3.62 -7.07 -9.45 -10.14 -8.95 -7.53 -6.38 1,2,4,5-tetrazine -1.97 -3.14 -6.88 -9.55 -10.32 -9.29 -7.86 -6.45 pentazine 0.09 -2.02 -6.25 -9.30 -10.07 -9.27 -7.84 -6.35 hexazine
    [Show full text]
  • Aromaticity and Relative Stabilities of Azines
    ORGANIC LETTERS 2010 Aromaticity and Relative Stabilities of Vol. 12, No. 21 Azines 4824-4827 Yan Wang,†,‡ Judy I-Chia Wu,‡ Qianshu Li,*,† and Paul von Rague´ Schleyer*,‡ School of Science, Beijing Institute of Technology, Beijing 100081, China, and Center for Computational Chemistry, Department of Chemistry, UniVersity of Georgia, Athens, Georgia 30602, United States [email protected]; [email protected] Received August 25, 2010 ABSTRACT The most refined nucleus-independent chemical shift index (NICS(0)πzz) and the extra cyclic resonance energies (ECREs), based on the block localized wave function (BLW) method, show that the aromaticity of all azines is like that of benzene. The same is true for aza-naphthalenes relative to naphthalene. The lower relative energies of isomers with vicinal N’s are due to the weakness of NN bonds rather than to reduced aromaticity. Does the aromaticity of benzene change when N atoms azines generally (“unless they form N-N bonds”). This substitute their CH groups sequentially? The answers in the analysis was based on the n-center delocalization index (n- literature diverge widely. We argue that nitrogen embedding DI), a measure of the degree of electron delocalization to should not decrease the strong diatropicity (aromaticity) of all atoms in an aromatic ring.4 benzene appreciably since this does not arise primarily from Quantitative analyses of the aromaticity of the whole azine having equal CC bond lengths and uniform π charge series have led to inconsistent conclusions.1,2c,4 Major distribution. Indeed,
    [Show full text]