DOCSLIB.ORG

UNITED STATES PATENT OFFICE 2,577,231 DIAZINE Sulfonamides and Methods of PRE PARING the SAME James W

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
UNITED STATES PATENT OFFICE 2,577,231 DIAZINE Sulfonamides and Methods of PRE PARING the SAME James W Patented Dec. 4, 1951 2,577,231 UNITED STATES PATENT OFFICE 2,577,231 DIAZINE suLFONAMIDES AND METHODs oF PRE PARING THE SAME James W. Clapp, Darien, and Richard O. Robin, Jr., Riverside, Conn., assignors to American Cyanamid Company, New York, N. Y., a corpo ration of Maine No Drawing. Application April 17, 1950, Serial No. 156,484 i4 Claims. (C. 260-250) 2 This invention relates to the preparation of One or more of the following substituents; an new Organic compounds. More particularly, it alkyl group, a halogen radical and the like. relates to diazine sulfonamides and their prep The compounds are, in general, white crystal aration. line solids having definite melting points and are It is generally recognized that numerous func is reasonably Soluble in Water. tions and actions of the human body are largely The compounds of the present invention are Controlled by a wide variety of enzymes. One of prepared by dissolving a mercaptodiazine in an these numerous enzymes is called carbonic anhy aqueous acid Solution and paSSing chlorine gas drase because it is involved in the netabolism of into Said solution to produce the corresponding carbon dioxide. This enzyme has other func Sulfonyl chloride. This product is then treated tions too, since it can catalyze the conversion With an exceSS of annonia in the form of liquid of carbon dioxide to carbonic acid. The excretion ammonia, or amonium hydroxide to produce the of acid by the kidneys is thought to be due to unsubstituted Sulfonamides and with an alkyl this function of carbonic anhydrase. anine, alkarylamine, arylamine or heterocyclic The excretion of acid by the kidneys is one anine to produce compounds Substituted on the method by which the body normally conserves Sulfonamide group. salt. The maintenance of a constant ratio of salt The reaction time is not too critical but chlo to water in the body is of utmost importance for rine should be added at such a rate that the general health. In some cases, however, excess temperature does not raise excessively and until salt and Water accumulate in the tissues causing an excess is present in the reaction mixture. The a condition which is called edema. It is frequent temperature during the chlorination is preferably ly encountered in a SSociation with congestive maintained within the range of -10° C. to 25° C. heart failure. The excess Salt and water cause When reacting the sulfonyl chloride with am an uncomfortable swelling of the tissues and monia, or the amine a higher temperature may be place an added Strain on the heart. To combat used up to 60° C. or higher. Obviously, the tem this condition. So-called diuretic agents are some perature for the amination should not be higher times used to promote the excretion of the excess than the boiling point of the particular amine salt and water. These agents, for the most part, used. in the past, have been mercury derivatives. Since The amines which may be used in the process these compounds contain mercury, they are not of the present invention may be primary amines Without toxicity on continued use and must be Such as methylamine, ethylamine, propylamine, administered by injection. phenylamine, para-methylphenylamine, benzyl Shortly after sulfanilamide came into wide amine, 2-aminothiazole and the like. Secondary spread use, Mann and Keilin, Nature, 146, 164 amines such as diethylamine, dipropylamine, di (1940), found that it, but none of the other sulfa is butylamine and the like can also be used. drugs, specifically inhibit the enzyme carbonic The compounds of the present invention were anhydrase. Within the past year or two sul found to be effective carbonic anhydrase inhibi fanilamide was experimentally used in several tors and may prove valuable in the relief of cases of congestive heart failure. While the sul edema, associated with congestive heart failure. fanilamide helped to promote the excretion of 40 or in other conditions where inhibition of car excess salt and water, it was not sufficiently ac bonic anhydrase is useful. They are also ac tive to be safely administered in adequate doses. tive, against certain micro-organisms. We have found that diazine sulfonamides show The following examples illustrate the prepara much greater activity than Sulfanilanide in in tion of representative diazine sulfonamides from hibiting carbonic anhydrase. The new coin 45 the corresponding mercaptodiazines. All parts pounds of the present invention may be illus are by Weight unless otherwise indicated. trated by the following general formula: EXAMPLE 1. R / 2-pyrimidinestlfonamide Dz-SON 50 Three parts of 2-mercaptopyrimidine are dis , R Solved in 75 parts of N hydrochloric acid. The in which R and R' are hydrogen, alkyl, alkaryl, solution is stirred in a cooling bath while chlorine aryl or heterocyclic radicals and Dz is a diazine is introduced through a capillary tube until the radical such as pyrimidine, pyrazine and pyrid color of excess dissolved chlorine is pronounced. azine. The diazine radical may have present 55 About thirty minutes is required. The tempera 2,577,281 3. 4. ture is held below 10° C. and preferably below 5° overnight. 100 parts of water are added, and the C. The precipitated solid is filtered and Washed mixture is stirred and acidified. The precipitated With a little ice-cold water. oil crystallizes on chilling and rubbing. It is The crude damp 2-pyrimidinesulfonyl chloride filtered, then resuspended in cold dilute acid, is added gradually to a large excess (about 350 stirred well, refiltered, and dried. It can be puri parts) of liquid ammonia. After about thirty fied by solution in ether, treatment with acti minutes, the excess ammonia, is allowed to eva wated charcoal, filtration, and removal of the porate and the residue is extracted with a Small Solvent. The pure compound is a White, Waxy, amount of diluate ammonium bydroxide. The crystalline solid, melting point 25.5-26 C. The extract is treated with activated charcoal, fil product is insoluble in water but soluble in most tered, and the filtrate made slightly acid, with organic solvents. chilling. If no precipitate forms, the Solution is EXAMPLE 6 concentrated. The product is filtered and dried. The product is recrystallized from a minimum 4,6-dimethyl-2-pyrimidinesulfon-p-toluide amount of water. The pure compound is a white 4,6-dimethyl-2-pyrimidinesulfonyl chloride is crystalline solid, melting point 180.5°-18 C., prepared and purified by the method previously With bubbling. described. Four parts of the Sulfonyl chloride EXAMPLE 2 are added gradually to 50 parts of p-toluidine in 5-chloro-2-pyrimidinesulfonamide 50 parts of dry pyridine, with stirring in a cool 2. ing bath. The Solid dissolves, and the mixture 5-chloro-2-mercaptopyrimidine is converted to is allowed to stand four hours. It is diluted. With the sulfonyl chloride by the method of Example water and acidified. A solid crystallizes On rub , Four parts of the mercapto compound is sus bing and chilling. It is filtered and washed pended in 100 parts of 1 N hydrochloric acid, and thoroughly with water. It is dissolved in dilute chlorine is introduced for about seventy-five min Sodium hydroxide, and the Solution is filtered lutes. The crude damp sulfonyl chloride is con and acidified. The precipitate is filtered and re verted to the sulfonamide with liquid ammonia. crystalized from a large Volume Of carbon-tetra by the method described above. The product is chloride. The pure compound is a White Crystal recrystallized from water. The pure compound line solid, melting point 180.5°-18°C. is a white crystalline solid, melting point about 3) 135°-40° C. EXAMPLE 7 EXAMPLE 3 4,6-dimethyl-2-pyrimidinesulfonbenaylamide 4,6-dimethyl-2-pyrimidinesulfonamide 4,6-dimethyl-2-pyrimidinesulfonyl chloride is 4,6-dimethyl - 2 - mercaptopyrimidine is con prepared as described in Example 1. Five parts verted to the sulfonyl chloride by the method of of Crude damp Sulfonyl chloride are added grad Example 1. 2.5 parts of the mercapto compound ually to 50 parts of benzylamine. The mixture are used, dissolved in 25 parts of 1 N hydrochloric was stirred for some time, then diluted with Water acid, and chlorine is passed in for about thirty and acidified. The precipitated solid is filtered minutes. The product can be purified by dis 40 and washed, then redissolved in dilute sodium solving in ether, drying the solution and remov hydroxide, and filtered. The filtrate is acidified ing the solvent in vacuo. The pure compound is and the product is filtered and recrystallized from a white crystalline solid, melting point 41-42 water. The pure compound is a white crystalline C. The crude damp Sulfonyl chloride is con solid, melting point 130.5-131 C. verted to the Sulfonanide in liquid annonia by EXAMPLE 8 the method desscribed above. It is recrystallized from water. The pure product is a White crystal N-(2-thidaolyl)-4,6-dimethyl-2-pyrimidines line solid, melting point 200-200.5 C., with bub Sulfonamide bling. Yield, 46% theory, based on mercapto 4,6-dimethyl-2-pyrimidinesulfonyl chloride is compound. prepared and purified as previously described. EXAMPLE 4 50 Four parts of the sulfonyl chloride are added gradually to a mixture of 40 parts of 2-amino 4,6-dimethyl-2-pyrimidinesulfon-n-progylamide thiazole and 50 parts of dry pyridine, with stirring 4,6-dimethyl-2-pyrimidinesulfonyl chloride is in a cooling bath. Continued stirring slowly gives prepared and purified as described in Example 3. complete solution. The pyridine is removed in Four parts of the Sulfonyl chloride are added 55 vacuo and the residue is diluted. With Water and gradually to 50 parts of dry n-propylamine with acidified.
Load more

Recommended publications
  • Heterocyclic Compounds with Biological Meaning
    Heterocyclic compounds with biological meaning 1 Heterocyclic compounds Cyclic, organic compounds which besides carbon atoms have one or more heteroatom (other elements than C). Heterocyclic atoms: – nitrogen, N – sulphur, S – oxygen, O – phosphorus, P – barium, Ba – zinc, Zn – silicon, Si. 2 Heterocyclic compounds From the biological point of view, the most important are heterocyclic compounds with 5- and 6-membered rings, containing: S, N, O. Most of the heterocyclic compounds have their common names. Substituent’s position in the ring is described by : – number – position of heteroatom – no. 1 – Greek letter – describes carbon atom the closest to heteroatom as a, then β and γ, respectively. 3 Heterocyclic compounds Heterocyclic compounds are: • widespread in nature • biologically active • some of them are toxic (e.g. coniine, coumarin and derivatives). Occurrence in: • natural dyes - heme, chlorophyll • alkaloids – atropine and nicotine • amino acids such as tryptophan and histidine • enzymes, nucleoproteins, antibiotics • vitamins • many synthetic pharmaceuticals. 4 Heterocyclic compounds Aromatic character of heteroatom-containing ring comes from aromatic sextet which consists of: • „not bound” electron pairs of heteroatoms • four electrons π from carbon atoms Pyrrole Furane Thiophen 5 5- membered ring heterocyclic compounds with one heteroatom 5-membered rings: • contain mostly oxygen, sulphur and nitrogen • are flat • are aromatic 6 5- membered ring heterocyclic compounds with two heteroatoms oxazole imidazole thiazole pyrazole 7 5- membered ring heterocyclic compounds With one heteroatom With two heteroatoms Condensation products with benzene 8 Pyrrole and derivatives • Pyrrole derivatives: • pyrroline • pyrrolidone • proline, • Hydroksyproline. • Condensation’s products of pyrrole with benzene: – indole, – tryptophan, – serotonin. • Condensation’s products of pyrrole with formaldehyde: – heme – hemoglobin – billirubin – porphyrins – Biliverdin.
    [Show full text]
  • Heterocyclic Compounds
    Gábor Krajsovszky Heterocyclic compounds ISBN: 978-615-5722-01-1 © Gábor Krajsovszky Responsible editor: Gábor Krajsovszky Publisher’s reader: István Mándity Translated by Péter Tétényi Department of Organic Chemistry Pharmaceutical Faculty Semmelweis University Budapest, 2018 Acknowledgements The editor wants to express many thanks to Dr. István Mándity, who is Associate Professor and Director of Department of Organic Chemistry, for the careful proofreading service of the current manuscript, as well as to Dr. Péter Tétényi, who is Assistant Professor, for the translation to English language. Moreover, the editor renders many thanks to Mrs. Ferenc Juhász and Ms. Nikoletta Zlatzky laboratory assistants for drawing material of the figures. Dr. Gábor Krajsovszky Associate Professor Department of Organic Chemistry Literature used Alan R. Katritzky, Charles W. Rees: Comprehensive Heterocyclic Chemistry Parts 2-3, 4-6, 7 Pergamon Press 1984 Oxford • New York • Toronto • Sydney • Paris • Frankfurt T. Eicher, S. Hauptmann, A. Speicher: The Chemistry of Heterocycles Structure, Reactions, Syntheses, and Applications Wiley-VCH GmbH 2003 Weinheim E. Breitmaier, G. Jung: Organische Chemie Grundlagen, Stoffklassen, Reaktionen, Konzepte, Molekülstruktur Georg Thieme Verlag 1978, 2005 Stuttgart • New York Clauder Ottó: Szerves kémia II/2. Egyetemi jegyzet Semmelweis OTE Budapest, 1980 Bruckner Győző: Szerves kémia III−1. Tankönyvkiadó, Budapest, 1964 Természettudományi Lexikon − Harmadik kötet Clauder Ottó: 'Heterociklusos vegyületek' címszó, 155-161.
    [Show full text]
  • Tetrazinebox: a Structurally Transformative Toolbox Qing-Hui Guo, Jiawang Zhou, Haochuan Mao, Yunyan Qiu, Minh T
    pubs.acs.org/JACS Article TetrazineBox: A Structurally Transformative Toolbox Qing-Hui Guo, Jiawang Zhou, Haochuan Mao, Yunyan Qiu, Minh T. Nguyen, Yuanning Feng, Jiaqi Liang, Dengke Shen, Penghao Li, Zhichang Liu, Michael R. Wasielewski, and J. Fraser Stoddart* Cite This: J. Am. Chem. Soc. 2020, 142, 5419−5428 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: Synthetic macrocycles capable of undergoing allosteric regulation by responding to versatile external stimuli are the subject of increasing attention in supramolecular science. Herein, we report a structurally transformative tetracationic cyclophane containing two 3,6-bis(4-pyridyl)-l,2,4,5-tetrazine (4-bptz) units, which are linked together by two p-xylylene bridges. The cyclophane, which possesses modular redox states and structural post-modifications, can undergo two reversibly consecutive two-electron reductions, affording first its bisradical dicationic counterpart, and then subsequently the fully reduced species. Furthermore, one single-parent cyclophane can afford effectively three other new analogs through box- to-box cascade transformations, taking advantage of either reductions or an inverse electron-demand Diels−Alder (IEDDA) reaction. While all four new tetracationic cyclophanes adopt rigid and symmetric box-like conformations, their geometries in relation to size, shape, electronic properties, and binding affinities toward polycyclic aromatic hydrocarbons can be readily regulated. This structurally transformative tetracationic cyclophane performs a variety of new tasks as a result of structural post-modifications, thus serving as a toolbox for probing the radical properties and generating rapidly a range of structurally diverse cyclophanes by efficient divergent syntheses. This research lays a solid foundation for the introduction of the structurally transformative tetracationic cyclophane into the realm of mechanically interlocked molecules and will provide a toolbox to construct and operate intelligent molecular machines.
    [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]
  • 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]
  • Haloselectivity of Heterocycles Will Gutekunst
    Baran Group Meeting Haloselectivity of Heterocycles Will Gutekunst Background SN(ANRORC) Addition of Nuclophile, Ring Opening, Ring Closure Polysubstituted heterocycles represent some of the most important compounds in the realm of pharmaceutical and material sciences. New and more efficient ways to selectively produce these Br Br molecules are of great importance and one approach is though the use of polyhalo heterocycles. Br NaNH2 N N Consider: Ar N 3 Ar2 NH3(l), 90% NH2 3 Halogenations H NH2 H N CO2Me Ar H 3 Suzuki Couplings 1 N CO2Me - Br H Ar 3 Ar2 1 Triple Halogenation NH2 NH CO Me N N 2 Ar1 H 1 Triple Suzuki Coupling N CO2Me N NH H NH2 Ar H 3 Ar2 1 Triple C-H activation? CO Me N 2 Ar1 H N CO2Me Cross Coupling H Virtually all types of cross coupling have been utilized in regioselective cross coupling reactions: Nucleophilic Substitution Kumada, Negishi, Sonogashira, Stille, Suzuki, Hiyama, etc. SNAr or SN(AE) In all of these examples, the oxidative addition of the metal to the heterocycle is the selectivity determining steps and is frequently considered to be irreversible. This addition highly resembles a nucleophilic substitution and it frequently follows similar regioselectivities in traditional S Ar reactions. Nu N The regioselectivity of cross coupling reaction in polyhalo heterocycles do not always follow the BDE's Nu of the corresponding C-X bonds. N X N X N Nu 2nd 2nd Meisenheimer Complex 1st Br Br 88.9 83.2 S (EA) Br 88.9 N 87.3 Br O O via: st OMe 1 Br NaNH , t-BuONa 2 N N pyrrolidine + Merlic and Houk have determined that the oxidative addition in palladium catalyzed cross coupling N N THF, 40ºC N reactions is determined by the distortion energy of the C-X bond (related to BDE) and the interaction of N the LUMO of the heterocycle to the HOMO of the Pd species.
    [Show full text]
  • October 2004 CLASSIFICATION DEFINITIONS 544 - 1
    October 2004 CLASSIFICATION DEFINITIONS 544 - 1 CLASS 544, ORGANIC COMPOUNDS -- PART OF THE CLASS 532-570 SERIES 9 This subclass is indented under subclass 8. Compounds wherein the thiadiazine ring is one of the cyclos of a polycyclo ring system. SUBCLASSES 10 This subclass is indented under subclass 9. 1 This subclass is indented under subclass 1. Compounds wherein the polycyclo ring system Compounds under Class 540, ... which contain consists of two rings, one of which is the thia- a six-membered hetero ring having two or diazine ring. more ring hetero atoms of which at least one is nitrogen. 11 This subclass is indented under subclass 10. Compounds wherein the bicyclo ring system SEE OR SEARCH CLASS: consists of the thiadiazine ring and a benzene 588, Hazardous or Toxic Waste Destruc- ring. tion or Containment, appropriate sub- classes for the chemical destruction of 12 This subclass is indented under subclass 11. hazardous or toxic waste. Compounds wherein the sulfur atom is in the 1- position and the nitrogen atoms are in the 2- 2 This subclass is indented under subclass 1. and 4-positions of the six-membered hetero Compounds wherein the six- membered hetero ring. ring includes at least one atom each of oxygen, sulfur, nitrogen and carbon and contains no (1) Note. An example of a structure pro- other elements as ring members. vided for herein is: 3 This subclass is indented under subclass 1. Compounds wherein the six- membered hetero ring includes at least one atom each of sulfur, nitrogen and carbon and contains no other ele- ments as ring members.
    [Show full text]
  • E4032922d5230c3b19df5adaef1
    Borneo Journal of Resource Science and Technology (2017) 7(2): 60-75 REVIEW PAPER Review on the Synthesis of Pyrazine and Its Derivatives KOK TONG ONG1, ZHI-QIANG LIU2 & MENG GUAN TAY*1 1Faculty of Resource Science and Technology, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak, Malaysia; 2State Key Lab of Crystal Materials, Shandong University, Jinan, 250100, China. *Corresponding author: [email protected] ABSTRACT Pyrazine is a kind of natural product which can be found in plants, animals, insects, marine organisms and microorganisms. The main function of pyrazine in living organisms is used as flavor of the raw foods. Pyrazine and its derivatives were also produced in industries mainly for fragrance, flavor and pharmaceutical applications. This review describes the historical development of pyrazine including the discovery and synthesis, to the recent synthetic approach of pyrazinium. In general, six synthetic approaches namely condensation reaction, ring closure, metal catalysis, green reaction, Maillard reaction and acid catalyst on N-substitution have been reviewed in this paper. The first five approaches are mainly aimed for the substitution at 2, 3, 5 and 6 positions in pyrazine ring, whereas the last approach is specifically for 1 and 4 positions in pyrazine. Keywords: Diazine, pyrazine, and Maillard reaction INTRODUCTION of nitrogen atoms that is positioned at para position (Sato, 2014). The specific dissociation Diazine is described as a compound with constant for pyrazine are pK = 0.65 and pK = - monocyclic aromatic ring that contains two a1 a2 5.78 (Dolezal & Zitko, 2015). nitrogen atoms with a molecular formula of C4H4N2. The three isomers of diazine are pyridazine, pyrimidine and pyrazine (Figure 1).
    [Show full text]
  • Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding Zixi Zhu, Christopher M
    pubs.acs.org/JACS Article Selective N1/N4 1,4-Cycloaddition of 1,2,4,5-Tetrazines Enabled by Solvent Hydrogen Bonding Zixi Zhu, Christopher M. Glinkerman, and Dale L. Boger* Cite This: J. Am. Chem. Soc. 2020, 142, 20778−20787 Read Online ACCESS Metrics & More Article Recommendations *sı Supporting Information ABSTRACT: An unprecedented 1,4-cycloaddition (vs 3,6-cycloaddition) of 1,2,4,5- tetrazines is described with preformed or in situ generated aryl-conjugated enamines promoted by the solvent hydrogen bonding of hexafluoroisopropanol (HFIP) that is conducted under mild reaction conditions (0.1 M HFIP, 25 °C, 12 h). The reaction constitutes a formal [4 + 2] cycloaddition across the two nitrogen atoms (N1/N4) of the 1,2,4,5-tetrazine followed by a formal retro [4 + 2] cycloaddition loss of a nitrile and aromatization to generate a 1,2,4-triazine derivative. The factors that impact the remarkable change in the reaction mode, optimization of reaction parameters, the scope and simplification of its implementation through in situ enamine generation from aldehydes and ketones, the reaction scope for 3,6-bis(thiomethyl)-1,2,4,5- tetrazine, a survey of participating 1,2,4,5-tetrazines, and key mechanistic insights into this reaction are detailed. Given its simplicity and breath, the study establishes a novel method for the simple and efficient one-step synthesis of 1,2,4-triazines under mild conditions from readily accessible starting materials. Whereas alternative protic solvents (e.g., MeOH vs HFIP) provide products of the conventional 3,6-cycoladdition, the enhanced hydrogen bonding capability of HFIP uniquely results in promotion of the unprecedented formal 1,4-cycloaddition.
    [Show full text]
  • Molecular Properties of the Valence Isomers of Diazines: Density Functional Theory (DFT) and Møller Plesset (Mp2) Methods
    International Journal of Modern Chemistry, 2018, 10(1): 117-137 International Journal of Modern Chemistry ISSN: 2165-0128 Journal homepage: www.ModernScientificPress.com/Journals/IJMChem.aspx Florida, USA Article Molecular Properties of the Valence Isomers of Diazines: Density Functional Theory (DFT) and Møller Plesset (mp2) Methods IBRAHIM, Asiata Omotayo, OYEBAMIJI Abel Kolawole and SEMIRE Banjo* Department of Pure and Applied Chemistry, Faculty of Pure and Applied Sciences, Ladoke Akintola University of Technology, PMB 4000, Ogbomoso, Oyo State, Nigeria * Author to whom correspondence should be addressed; E-Mail: [email protected] Article history: Received 20 February 2018, Revised 25 April 2018, Accepted 30 April 2018, Published 21 May 2018. Abstract: Density functional theory (B3LYP) and Moller-Plesset perturbation theory to the second order (MP2) methods with 6-31G(d),6-31+G(d,p), 6-311G (d,p), 6-311+G(d,p) and 6-311++G(d,p) basis sets have been used to investigate some diazine isomers. The equilibrium geometries, relative stabilities, strain energies, vibrational frequencies and global nucleophilicity indices for fifteen isomers are reported. The relative energies show that Dewar isomers (except 1,4-DBHD) are more stable compared to the Diazyl-isomers. The isomers with N-N and/or N-C bonds in the center are less stable, this is observed for both Dewar and Diazyl-isomers; therefore nitrogen atom(s) in the center of the isomers decreases the stability. Keywords: Diazines, relative stabilities, nucleophilicity index, quantum mechanical methods 1. Introduction Pyridazines are diazines group of compounds that are formally derived from benzene by the Copyright © 2018 by Modern Scientific Press Company, Florida, USA Int.
    [Show full text]
  • Chemistry from the Boger Research Group
    Chemistry from the Boger Research Group A Synergy of Target-Oriented Synthesis and New Reaction Development: Cycloadditions for the Formation of Highly-Functionalized Ring Structures and Applications in Total Synthesis Troy E. Reynolds January 8, 2007 Dale L. Boger Education B.S. University of Kansas, 1975 Ph.D. Harvard University, 1980 - E. J. Corey "Part I: New annulation processes, Part II: Studies directed toward a biomimetic synthetic approach to prostaglandins" Professional Career Assistant Professor/Associate Professor, University of Kansas 1979-1985 Associate Professor/Professor, Purdue University, 1985-1991 Professor, The Scripps Research Institute, 1991-present Awards Searle Scholar Award 1981-1984 NIH Career Award 1983-1988 Alfred P. Sloan Fellow 1985-1989 ACS Arthur C. Cope Scholar Award, 1988 Japan Promotion of Science Fellow, 1993 ISHC Katritzky Award in Heterocyclic Chemistry, 1997 Honorary Member, The Lund Chemical Society (Sweden), 1998 ACS Aldrich Award for Creativity in Organic Synthesis, 1999 A. R. Day Award, POCC 1999 Honorary Ph.D. Degree: Laurea Honors Causa, Univ. of Ferrara, 2000 Smissman Lecturer, Univ. of Kansas, 2000 Yamanouchi USA Faculty Award, 2000 Paul Janssen Prize for Creativity in Organic Synthesis, 2002 oss Lecturer, Dartmouth College, 2002 Fellow, American Association for the Advancement of Science, 2003 Adrien Albert Medal, Royal Society of Chemistry, 2003 ISI Highly Cited (top 100 chemists) Alder Lecturer, University of Köln, 2005 Chemistry from the Boger Research Group Research Interests •Total synthesis •New synthetic methods •Bioorganic and medicinal chemistry •Combinatorial chemistry •DNA-agent interactions •Chemistry of antitumor antibiotics Cycloaddition Reactions I. Heteroaromatic Azadienes Roseophilin II. N-Sulfonyl-1-Azadienes •Mechanism/Reactivity Piericidin A1 •Scope/Limitations •Utility/Application III.
    [Show full text]
  • An Introduction to Heterocyclic Chemistry
    An Introduction to Heterocyclic Chemistry Reference: A Textbook of Organic Chemistry, Tewari and Vishnoi This is only the introduction part of the unit on heterocyclic chemistry. Please refer textbook for detailed information. Introduction Cyclic compound having only carbons as the ring members, such as benzene are called carbocyclic compounds. As only carbon forms the backbone of the ring, it is also a homocyclic compound. H H γ H H H H C C C C 4 β' C C β Heterocyclic Pyridine Carbocyclic Benzene 5 3 with one α' 6 2 α C C C 1 C Nitrogen Heteroatom C N H H H H H Figure 1: Structure of Homocyclic Benzene and Heterocyclic Pyridine In contrast, cyclic compounds having at least one atom other than carbon as ring members, (e.g. Pyridine with nitrogen replacing one of the carbon atom) may be termed as heterocyclic compounds . These atoms are termed as heteroatoms . The structure of benzene and pyridine are provided in figure 1 above. Nomenclature of Heterocyclic Compounds Heterocyclic compounds are popularly known by their common names. However, IUPAC has provided a systematic nomenclature with prefix and suffix as discussed below. According to IUPAC, the numbering starts with the heteroatom as shown in figure 1. According to common names, the greek letters, α, β, γ etc are followed as shown in figure 1. Order of Seniority Prefix Suffix 1 Oxa for oxygen 2 Thia for sulfur -ole for 5 membered rings 3 Aza for nitrogen -ine for 6 membered rings 4 Phoshpha for phosphorus -epine for 7 membered rings 5 Bora for boron Table 1: Nomenclature of Heterocyclic compounds When more than one heteroatom is present in a molecule, an order of seniority exists for the naming and numbering system, with the number preference given for oxygen first followed by 1 other atoms as shown.
    [Show full text]