DOCSLIB.ORG

A Novel Hydantoin Synthesis and Exploration of Related Reactions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
A Novel Hydantoin Synthesis and Exploration of Related Reactions A novel hydantoin synthesis and exploration of related reactions PhD thesis By Matthew Leonard Chemistry building, RMIT, Melbourne January 2015 Primary Supervisor: Julie Niere Second Supervisor: Peter McKay Postdoctoral Consultant: Anthony Lingham A novel hydantoin synthesis and exploration of related reactions A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Matthew Johnathan Leonard B.Sc., La Trobe Honours, RMIT School of Applied Sciences College of Science Engineering and Health RMIT University October 2015 Declaration I certify that except where due acknowledgement has been made, the work is that of the author alone; the work has not been submitted previously, in whole or in part, to qualify for any other academic award; the content of the thesis/project is the result of work which has been carried out since the official commencement date of the approved research program; any editorial work, paid or unpaid, carried out by a third party is acknowledged; and, ethics procedures and guidelines have been followed. Matthew Johnathan Leonard 04-OCT-2015 A novel hydantoin synthesis and exploration of related reactions Abstract Chapter one gives a short history of the discovery of hydantoins, followed by their chemical properties and reactivity and concluding with the many ways to date that they have been synthesized. In chapter two, a hydantoin compound RU58841, which is a popular anti-baldness agent is synthesized by an alternative pathway to those previously presented. The new synthesis gives 33% overall yield and avoids the hazardous reagent phosgene. Chapter three explores the novel bromo–nitro substitution reaction. The reaction rate has been characterized by using a library of compounds and possible mechanisms for this reaction have been presented after consideration of the results of a Hammett plot. In chapter four, another novel step from the alternative synthesis of RU58841 is explored. This reaction involves 2-nitropropane as a leaving group to create an isocyanate intermediate which gives a hydantoin upon ring closure. Attempts and progress towards preparing isocyanate compounds using this method are discussed. Chapter five summarizes the key findings and describes the future directions that can be taken with the new chemistry presented in this thesis. ii © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions To my many good friends and colleagues We are the music makers, And we are the dreamers of dreams, Wandering by lone sea-breakers, And sitting by desolate streams. World-losers and world-forsakers, Upon whom the pale moon gleams; Yet we are the movers and shakers, Of the world forever, it seems. With wonderful deathless ditties We build up the world’s great cities, And out of a fabulous story We fashion an empire’s glory: One man with a dream, at pleasure, Shall go forth and conquer a crown; And three with a new song’s measure Can trample an empire down. We, in the ages lying In the buried past of the earth, Built Nineveh with our sighing, And Babel itself with our mirth; And o’erthrew them with prophesying To the old of the new world’s worth; For each age is a dream that is dying, Or one that is coming to birth. Arthur William Edgar O’Shaughnessy iii © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions Acknowledgments Despite many stressful and challenging changes in circumstance, I have managed to carry out the high quality work that you are about to read. I changed primary supervisor two times and second supervisor one time during my candidature. I was married two times during my PhD, for the first time in the second month of my PhD candidature which lasted for 18 months and ended in September 2012. In November 2012 I began a new relationship and two years later I was married for a second time, only two months before the submission of this thesis. I would like to thank both of my wives, Jennifer and Yvonne for their support throughout my candidature. My Postdoctoral consultant Anthony Lingham shares many good ideas with me and I look forward to us going into business together. iv © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions Table of contents 1. A general introduction to hydantoins, their properties & preparations 1.1 The hydantoin moiety 1.1.1 Chemical properties 1.1.2 Reactivity of the hydantoin ring 1.1.3 Discovery of hydantoins 1.2 Natural products containing the hydantoin moiety 1.3 Commercial compounds containing the hydantoin moiety 1.3.1 Anti-microbial hydantoins 1.3.2 Neuroactive hydantoins 1.3.3 Androgen inhibitors 1.4 Preparations of hydantoins 1.4.1 Synthesis by Biltz et. al. via benzylic rearrangement 1.4.2 Preparation via the Read hydantoin synthesis 1.4.3 Development of the Bucherer-Bergs reaction 1.4.4 Solid phase hydantoin preparations 1.4.5 Other synthetic routes to hydantoin derivatives 1.4.6 Summary of hydantoin preparations 1.4.7 Installment of substituents to the hydantoin ring 1.5 Preparation of N-aryl hydantoins 1.5.1 Formation via N-aryl isocyanates 1.5.2 Aryl hydantoins by catalytic organometallic coupling and by halo nucleophilic aromatic substitution 1.5.3 Carbamate cyclization 1.5.4 A new pathway for the synthesis of N-aryl hydantoins 2. A new synthesis of the N-aryl hydantoin RU58841 2.1 The target compound RU58841 2.1.1 Existing syntheses of RU58841 2.2 Retrosynthetic analysis of RU58841 2.3 New synthetic route to RU58841 2.4 Novel ring closure 2.5 Experimental procedures and compound characterization v © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions 3. Investigation into the mechanism of Br–NO2 substitution on tertiary α-carbons 3.1 Introduction 3.2 Halo−nitro substitutions: the Kornblum reaction 3.3 Kornblum and the SN1/SN2 dichotomy 3.3.1 Mechanistic evidence from ambident nucleophiles 3.3.2 Stereochemical evidence 3.3.3 Other evidence 3.4 Tertiary halo−nitro substitution α to a carbonyl 3.4.1 Mechanism of tertiary halo−nitro substitution α to a carbonyl 3.4.1.1 Rate measurements 3.4.1.2 Rate dependence on nitrite concentration 3.4.1.3 Hammett plots 3.5 Experimental procedures and compound characterization 3.5.1 Acylation reactions 3.5.2 Substitution reactions 3.5.2.1 Br−NO2 Substitution in the absence of O2 3.5.2.2 Br−NO2 Substitution at low nitrite concentration 4. 2-Nitropropane – A new leaving group and novel formation of an isocyanate 4.1 Properties of 2-nitropropane 4.1.1 Separation and capture of 2-nitropropane formed 4.2 Properties of the isocyanate group 4.2.1 Existing preparations of the isocyanate group 4.3 Mechanistic considerations 4.3.1 Trapping isocyanate intermediate 4.4 Towards preparation of discrete isocyanate compounds using this route. 4.5 Experimental procedures and compound characterization 5. Key findings and Future work 5.1 Outcomes and applications 5.2 Further work 5.2.1 RU58841 synthesis vi © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions 5.2.1.1 Analogues of RU58841 5.2.1.2 Blaise reaction on intermediates 5.2.1.3 Synthesis of useful peptide macrocycles 5.2.2 Bromo–nitro substitution 5.2.3 Isocyanates from α nitroisobutyranilides with 2-nitropropane leaving group 6. References and Appendices 6.1 References 6.2 Appendix I: Data from Br−NO2 substitution rates 6.3 Appendix II: Plots of ln(% start material) against time for Br−NO2 substitution 6.4 Appendix III: Hammett plots 6.5 Appendix IV: Fragmentation patterns of isocyanates obtained from α nitroisobutyranilides on GC MS injector port compared with those from SDBS 6.6 Appendix V: IR and NMR spectra of novel compounds vii © Matthew Leonard 2014 A novel hydantoin synthesis and exploration of related reactions 1. A general introduction to hydantoins, their properties & preparations 1.1 The hydantoin moiety A hydantoin (IUPAC “imidazolidine-2,4-dione”) is a 5-membered ring with two nitrogens in the ring. There are two carbonyls in the ring, one of them between the two nitrogens. The five positions of the ring are numbered and, as such, there are four points of functionality, one at the 1 position, one at the 3 position and two at the 5 position. The hydantoin moiety While it is possible for the carbon at position 5 to act as a chiral centre when bound to two different functional groups, positions 1–4 are mostly rigid and planar. If the oxygen at the 2 or the 4 position is replaced by a sulphur, the structure is known as a 2-thiohydantoin or 4-thiohydantoin respectively. When all four points of functionality are hydrogen, the compound is known as ‘hydantoin’ (2): a white solid with m.p. 220 °C. Hydantoins are sometimes mistakenly referred to as imidazoles; they are not, although the locations on the ring are numbered the same way and they can be formally formulated as dihydroxyimidazoles. Although imidazoles and hydantoin compounds have both been used as antibiotics, they each offer quite different chemistry and differ in their robustness and reactivity. This is mostly a function of the different properties of amides and amines. The hydantoin moiety can be more closely compared with the barbiturate moiety as its nitrogens behave in a similar way and it has two points of functionality at the 5 position. Like barbiturates, hydantoins can be substituted at one or both nitrogens, although the two nitrogens on a hydantoin are, unlike the barbiturate, not equivalent. Only one is an imide, the other being an amide and amides behave somewhat differently.
Load more

Recommended publications
  • (From the Department of Physiology, University of Minnesota, Minneapolis) Same Journal. N. K., Kolloid-Z., 1929, 47, 101. the Jo
    THE STRUCTURE OF THE COLLODION MEMBRANE AND ITS ELECTRICAL BEHAVIOR II, THE ACTIVATED COLLODION MEMBRANE BY KARL SOLLNER, IRVING ABRAMS, AND CHARLES W. CARR (From the Department of Physiology, University of Minnesota, Minneapolis) (Received for pubfication, March 31, 1941) I In preceding communicationst, 2 we were led to the conclusion that the elec- trochemical activity of collodion membranes, as manifested by concentration potentials, etc., is due principally to acidic impurities. Accordingly, different brands of collodion differ widely as to their activity, the purer brands being less active. The impure (but active) foreign brands of collodion, heretofore generally used by workers in the field of electrochemical membrane investiga- tion, are no longer obtainable. In order to continue our investigation, it became necessary to find methods to produce active collodion membranes at will. The idea of inducing changes in the electrochemical characteristics of mem- branes is not entirely new. Many investigators have activated membranes by the adsorption of proteins, e.g. the proteinized membranes of Loeb. 8 Other investigators use other organic compounds, usually dyestuffs. These may be adsorbed like proteins or they may be dissolved in the collodion solution* pre- vious to casting the membranes. Such membranes are interesting and useful in their own right, but are not altogether satisfactory substitutes for active collodion membranes. They very often show considerable asymmetry; more- over, the dyestuffs so far employed (according to the literature) are slowly re- leased into the solution in contact with the membrane, whereby the character of the membrane is considerably changed. Meyer and Sievers5 used an oxida- tion method to activate a cellophane membrane.
    [Show full text]
  • NACE Bromine Chemistry Review Paper
    25 YEARS OF BROMINE CHEMISTRY IN INDUSTRIAL WATER SYSTEMS: A REVIEW Christopher J. Nalepa Albemarle Corporation P.O. Box 14799 Baton Rouge, LA 70898 ABSTRACT Bromine chemistry is used to great advantage in nature for fouling control by a number of sessile marine organisms such as sponges, seaweeds, and bryozoans. Such organisms produce small quantities of brominated organic compounds that effectively help keep their surfaces clean of problem bacteria, fungi, and algae. For over two decades, bromine chemistry has been used to similar advantage in the treatment of industrial water systems. The past several years in particular has seen the development of several diverse bromine product forms – one-drum stabilized bromine liquids, all-bromine hydantoin solids, and pumpable gels. The purpose of this paper is to review the development of bromine chemistry in industrial water treatment, discuss characteristics of the new product forms, and speculate on future developments. Keywords: Oxidizing biocide, bleach, bromine, bromine chemistry, sodium hypobromite, activated sodium bromide, Bromochlorodimethylhydantoin, Bromochloromethyethylhydantoin, Dibromodi- methylhydantoin,, BCDMH, BCMEH, DBDMH, stabilized bromine chloride, stabilized hypobromite INTRODUCTION Sessile marine organisms generate metabolites to ward off predators and deter attachment of potential micro- and macrofoulants. Sponges, algae, and bryozoans for example, produce a rich variety of bromine-containing compounds that exhibit antifoulant properties (Fig. 1).1,2,3 Scientists are actively studying these organisms to understand how they maintain surfaces that are relatively clean and slime- free.4 Brominated furanones isolated from the red algae Delisea pulchra, for example, have been found to interfere with the chemical signals (acylated homoserine lactones) that bacteria use to communicate with one another to produce biofilms.5,6 This work may eventually lead to more effective control of microorganisms in a number of industries such as industrial water treatment, oil and gas production, health care, etc.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 6,270,722 B1
    USOO6270722B1 (12) United States Patent (10) Patent No.: US 6,270,722 B1 Yang et all e 45) Date of Patent:e Aug. 7, 2001 (54) STABILIZED BROMINE SOLUTIONS, (56) References Cited METHOD OF MANUFACTURE AND USES THEREOF FOR BOFOULING CONTROL U.S. PATENT DOCUMENTS 3,328.294 6/1967 Self et al.. (75) Inventors: Shunong Yang; William F. McCoy, 3,558,503 1/1971 Goodenough et al.. both of Naperville; Eric J. Allain, 3,767,586 10/1973 Rutkiewic et al.. Aurora; Eric R. Myers, Aurora; 5,683,654 11/1997 Dalmier et al.. Anthony W. Dalmier, Aurora, all of IL 5,795,487 8/1998 Dalmier et al.. (US) 6,007,726 * 12/1999 Yang et al. ........................ 422/37 X 6,015,782 1/2000 Petri et al. ........................... 510/379 (73) Assignee: Nalco Chemical Company, Naperville, 6,110,387 * 8/2000 Choudhury et al. ................. 210/752 IL (US) FOREIGN PATENT DOCUMENTS (*) Notice: Subject to any disclaimer, the term of this WO 97/20909 6/1997 (WO). patent is extended or adjusted under 35 WO 97/43392 11/1997 (WO). U.S.C. 154(b) by 0 days. * cited by examiner Primary Examiner Elizabeth McKane (21) Appl. No.: 09/283,122 (74) Attorney, Agent, or Firm-Kelly L. Cummings; (22) Filed: Mar. 31, 1999 Thomas M. Breininger (51) Int. Cl." ................................ A61L 2/16; C01B 709; (57) ABSTRACT D06L 3/06 Stabilized bromine Solutions are prepared by combining a (52) U.S. Cl. ..................................... 422/37; 422/6; 8/107; bromine Source and a Stabilizer to form a mixture, adding an 8/137; 162/1; 423/500; 252/187.2 oxidizer to the mixture, and then adding, an alkaline Source (58) Field of Search ...................................
    [Show full text]
  • Commission Delegated Regulation (Eu
    8.2.2019 EN Official Journal of the European Union L 37/1 II (Non-legislative acts) REGULATIONS COMMISSION DELEGATED REGULATION (EU) 2019/227 of 28 November 2018 amending Delegated Regulation (EU) No 1062/2014 as regards certain active substances/product- type combinations for which the competent authority of the United Kingdom has been designated as the evaluating competent authority (Text with EEA relevance) THE EUROPEAN COMMISSION, Having regard to the Treaty on the Functioning of the European Union, Having regard to Regulation (EU) No 528/2012 of the European Parliament and of the Council of 22 May 2012 concerning the making available on the market and use of biocidal products (1) and in particular the first subparagraph of Article 89(1) thereof, Whereas: (1) Commission Delegated Regulation (EU) No 1062/2014 (2) sets out in its Annex II a list of active sub­ stance/product-type combinations included in the programme of review of existing active substances contained in biocidal products (‘review programme’). (2) The competent authority of the United Kingdom of Great Britain and Northern Ireland (‘the United Kingdom’) is the evaluating competent authority for several active substance/product-type combinations listed in Annex II to Delegated Regulation (EU) No 1062/2014. (3) The United Kingdom submitted on 29 March 2017 the notification of its intention to withdraw from the Union pursuant to Article 50 of the Treaty on European Union. As a result, the United Kingdom will withdraw from the Union on 30 March 2019 and the Union legislation will no longer apply to and in the United Kingdom.
    [Show full text]
  • United States Patent (19) 11 Patent Number: 5,011,997 Hazen Et Al
    United States Patent (19) 11 Patent Number: 5,011,997 Hazen et al. (45) Date of Patent: Apr. 30, 1991 54 PROCESS FOR 2,822,396 2/1958 Dent ............................... 564/414 X BIS(4-AMINOPHENYL)HEXAFLUOROPRO. 3,897,498 7/1975 Zengel et al. ....................... 564/44 PANE 3,904,69 9/1975 Carnmam et al. ............. 564/414 X 4,082,749 4/1978 Quadbeck-Seeger et al. ..... 564/44 (75) Inventors: James R. Hazen, Coventry; William X R. Lee, E. Providence, both of R.I. 4,198,348 4/1980 Bertini et al. ....................... 564/44 (73) Assignee: Hoechst Celanese Corp., Somerville, OTHER PUBLICATIONS N.J. Houben-Weyl, "Stickstoff Verbindungen', Methoden 21 Appl. No.: 105,857 der Organischen Chemie, vol. 10, Part 3, pp. 375–377 (1965). 22 Fied: Oct. 7, 1987 Primary Examiner-Glennon H. Hollrah 51 Int. C. ................... CO7C 211/50; CO7C 209/50 Attorney, Agent, or Firm-Perman & Green (52) U.S.C. .................................... 564/335; 564/330; 564/414 57 ABSTRACT 58 Field of Search ............... 564/330, 158, 335, 181, This invention is an improved process for preparing 564/.414 2,2-bis(4-aminophenyl)hexafluoropropane which com prises subjecting 2,2-bis(4-aminocarbonylphenyl)hexa 56) References Cited fluoropropane to the Hofmann reaction and then treat U.S. PATENT DOCUMENTS ing that reaction product under reducing conditions to 902,150 0/1908 Heidenreich ................... 564/414 X produce the desired amine in high yield. 1,850,526 3/1932 Zitscher .......................... 564/.414 X 2,334,201 11/1943 Kamm et al. ................... 564/414 X 7 Claims, No Drawings 5,011,997 1.
    [Show full text]
  • 1. Give the Correct Names for Each of the Compounds Listed Below. A
    1. Give the correct names for each of the compounds listed below. a) NaCl sodium chloride n) ZrS2 zirconium sulfide b) FrBr francium bromide o) AgI silver iodide c) KF potassium fluoride p) BaSe barium selenide d) RaS radium sulfide q) MgO magnesium oxide e) LiI lithium iodide r) LaBr3 lanthanum bromide f) Li3N lithium nitride s) Sr3N2 strontium nitride g) AlBr3 aluminum bromide t) Cd3As2 cadmium arsenide h) CdCl2 cadmium chloride u) Rb2Se rubidium selenide i) K2O potassium oxide v) Rb3N rubidium nitride j) InF3 indium fluoride w) BaF2 barium fluoride k) ZnO zinc oxide x) ZrTe2 zirconium telluride l) Y2O3 yttrium oxide y) Cs3P cesium phosphide m) CaTe calcium telluride z) Y2O3 yttrium oxide 2. Write the correct chemical formula for each of the following compounds. a) potassium bromide KBr n) potassium nitride K3N b) zinc bromide ZnBr2 o) aluminum bromide AlBr3 c) lithium iodide LiI p) zinc phosphide Zn3P2 d) scandium chloride ScCl3 q) magnesium sulfide MgS e) magnesium chloride MgCl2 r) hafnium chloride HfCl4 f) magnesium oxide MgO s) barium sulfide BaS g) hydrogen sulfide H2S t) tantalum oxide Ta2O5 h) gallium iodide GaI3 u) zirconium nitride Zr3N4 i) sodium oxide Na2O v) potassium selenide K2Se j) magnesium selenide MgSe w) germanium fluoride GeF4 k) calcium fluoride CaF2 x) francium phosphide Fr3P l) aluminum oxide Al2O3 y) zinc arsenide Zn3As2 m) beryllium chloride BeCl2 z) scandium telluride Sc2Te3 L. h. s. – Chemistry – Nomenclature – Answers – Page 1 3. Give the correct names for each of the compounds listed below. a) CaSO4 calcium
    [Show full text]
  • PRIZE LIST 2010 Edited by Viral
    PRICE LIST 2013 NILE CHEMICALS pH INDICATORS , BIOLOGICAL STAINS CATALYST FOOD COLOURS CHEMICALS (LAB & BULK) REAGENTS (LAB & BULK) LABO ATORY REAGENTS & FINE CHEMICALS PRODUCT PROFILE PURE, EXTRA PURE, PURIFIED We have pure , extra pure and purified products , available as per buyers requirements and specifications. GUARANTEED REAGENTS (GR) Our Guaranteed Reagents are used for analytical and research work, where high purity is essential. This is similar to grade marketed by other International company. HPLC GRADE This are high performance chemicals , used in liquid chromatography used frequently in biochemistry and analytical chemistry to separate, identify, and quantify compounds SPECTROSCOPY GRADE These are solvents of high optical purity for UV/Visible/IR/Fluorescence/NMR and Mass spectroscopy. BIOLOGICAL STAIN Our Ph Indicators are ready to use solutions for Microbiology, Histology, Hematology and Cytology and are at par with certified grade stains as per International norms. Address : 202,Matruchhay ,378 /80 Narshi Natha Street ,Masjid , Mumbai -400 009 INDIA Email : [email protected] Tel: 91 22 66313162 : Fax : 91 22 23454828 Web site www.nilechemicals.com NILE CHEMICALS EXPLOSIVES: Certain Substances reacts exothermically, generating gases, which may explode on heating, hence storage may be required in water or suitable solvent OXIDISING:Some Substance reacts with oxygen and may cause fire hazard TOXIC:Certain substance on contact with human body may cause acute or chronic damage HARMFUL:Certain substance on contact with human body may cause acute or chronic damage FLAMABLE:Chemicals , Solvents with a flash point below zero degree and boiling point of 35 deg c are termed as flammable items CORROSIVE:Substance which causes severe damage to living tissues IRRITANT:Substance which causes irritation on contact with skin etc DANGEROUS: substance which causes damages to ecosystem RADIOACTIVE:Substance which evolves radiation in the ecosystem NILE CHEMICALS PRICE LSIT 2013 CAT.NOS.
    [Show full text]
  • Sodium Chlorite Handbook
    SODIUM CHLORITE HANDBOOK OxyChem Technical Information 01/2015 Dallas-based Occidental Chemical Corporation is a leading North American manufacturer of basic chemicals, vinyls and performance chemicals directly and through various affiliates (collectively, OxyChem). OxyChem is also North America's largest producer of sodium chlorite. As a Responsible Care® company, OxyChem's global commitment to safety and the environment goes well beyond compliance. OxyChem's Health, Environment and Safety philosophy is a positive motivational force for our employees, and helps create a strong culture for protecting human health and the environment. Our risk management programs and methods have been, and continue to be, recognized as some of the industry's best. OxyChem offers an effective combination of industry expertise, experience, on line business tools, quality products and exceptional customer service. As a member of the Occidental Petroleum Corporation family, OxyChem represents a rich history of experience, top-notch business acumen, and sound, ethical business practices. HB-600 2 01/2015 Table of Contents Introduction to Sodium chlorite ................................................................................................................. 4 Manufacturing ................................................................................................................................................ 4 Sodium Chlorite End Uses ............................................................................................................................
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8,293,918 B2 Modi Et Al
    US008293918B2 (12) United States Patent (10) Patent No.: US 8,293,918 B2 Modi et al. (45) Date of Patent: Oct. 23, 2012 (54) PROCESS FOR PRODUCING (52) U.S. Cl. ....................................................... 54.6/345 DHALOPYRIDINES (58) Field of Classification Search ........................ None See application file for complete search history. (75) Inventors: Gelebith H. Modi, Noida (IN); Anil Kumar Tyagi, Noida (IN); Ashutosh Agarwal, Noida (IN); Hem Chandra, (56) References Cited Gajraula (IN); Nikhilesh Chandra Bhardwaj, Gajraula (IN); Pradeep FOREIGN PATENT DOCUMENTS Kumar Verma, Gajraula (IN) WO WO 2005070888 A2 * 8, 2005 (73) Assignee: Jubilant Organosys Limited, Noida OTHER PUBLICATIONS (IN) Kovacic J Amer Chem Soc 1954 vol. 76 pp. 5491-5494.* Streitwieser, A. et al., Introduction to Organic Chemistry, 4th ed., (*) Notice: Subject to any disclaimer, the term of this 1992, p. 793.* patent is extended or adjusted under 35 Sigma-Aldrich Catalogue, 2009-2010, p. 2717.* U.S.C. 154(b) by 315 days. * cited by examiner (21) Appl. No.: 12/641,926 Primary Examiner — Janet Andres (22) Filed: Dec. 18, 2009 Assistant Examiner — Heidi Reese (74) Attorney, Agent, or Firm — Oblon, Spivak, (65) Prior Publication Data McClelland, Maier & Neustadt, L.L.P. US 2010/0160641 A1 Jun. 24, 2010 (57) ABSTRACT (30) Foreign Application Priority Data Disclosed herein an improved process for producing 2.3- (IN) ........................... 2891 (DELA2008 dihalopyridine with high purity at industrial scale with mini Dec. 19, 2008 mum effluent. (51) Int. C. C07D 21 1/72 (2006.01) 23 Claims, No Drawings US 8,293,918 B2 1. 2 PROCESS FOR PRODUCING 3-aminopyridine with oxydol at a molar ratio of 1:1 in con DHALOPYRIDINES centrated hydrochloric acid at 6-8°C.
    [Show full text]
  • Of Polymyxin B Solutions
    OpenAIR@RGU The Open Access Institutional Repository at Robert Gordon University http://openair.rgu.ac.uk Citation Details Citation for the version of the work held in ‘OpenAIR@RGU’: SAOHIN, W., 1997. Studies on the stability and activity of polymyxin B solutions. Available from OpenAIR@RGU. [online]. Available from: http://openair.rgu.ac.uk Copyright Items in ‘OpenAIR@RGU’, Robert Gordon University Open Access Institutional Repository, are protected by copyright and intellectual property law. If you believe that any material held in ‘OpenAIR@RGU’ infringes copyright, please contact [email protected] with details. The item will be removed from the repository while the claim is investigated. STUDIES ON THE STABILITY AND ACTIVITY OF POLYMYXIN B SOLUTIONS WIPAWEE SAOHIN A thesis submitted for the degree of DOCTOR OF PHILOSOPHY School of Pharmacy The Robert Gordon University Aberdeen United Kingdom SEPTEMBER 1997 To my parents, for their love, support and understanding . 1 Acknowledgements I am deeply indebted to Prof. R. M. E. Richards for his supervision, encouragement, patience and support throughout my study. I am also grateful to Prof. R. B. Taylor for his supervision and advice in the analytical work and to Prof. K. E. Kendle and Mr. Alex Wilson for their statistical advice. My thanks are also due to Dr. D. K. L. Xing, Dr. 1. Z. Xing and Miss Vivienne Hamilton for technical assistance in the microbiological work, Mr. Raymond Reid, Mrs. Lynn Hardie and Mrs. Ann Low in the analytical work. Support from academic and technical staff in the School of Pharmacy was invaluable throughout this work.
    [Show full text]
  • New Reactions of Nitro Compounds
    This dissertation has been 62-2176 microfilmed exactly as received KAPLAN, Ralph Benjamin, 1920- NEW REACTIONS OF NITRO COMPOUNDS. The Ohio State University, Ph.D., 1950 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan NEW REACTIONS OF NITRO COMPOUNDS DISSERTATION Presented In Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of the Ohio State University By RALPH B. KAPLAN, B.A., The Ohio State University 1950 Approved by: Adviser TABLE OF CONTENTS Page INTRODUCTION Acknowledgments Statement of the Problem SECTION I REACTION OF SODIUM NITROALKANES WITH VARIOUS NITRATING AGENTS 1 I. Discussion 1 A. Introduction 1 B. Agents Investigated 2 1. Nltryl Chloride 2 a. Preparation 2 b. Review of thé Reactions of Nltryl Chloride With Organic Reagents U c. Reaction of Sodium 2-Nltropropane With Nltryl Chloride 6 d. Reaction of Sodium 2-Nltropropane with Nltryl Chloride and Aluminum Chloride 11 2. Mixed Nitric and Sulfuric Acid 12 a. Reaction of Sodium 2-Nltropropane With Mixed Nitric and Sulfuric Acid 12 3. Methyl Nitrate Ih a. Reaction of Sodium 2-Nltropropane and of Potassium Nltroethane l4 I. Alkyl Nitrates as Nitrating Agents 14 II. Discussion of Results 15 Page II. Experimental 21 A. Agents Investigated 21 1. Nltryl Chloride 21 a. Preparation 21 1. Intermediates; Chlorosulfonlc Acid and Nitric Acid, Anhydrous 11. Procedure for Making Nltryl-Chloride h. Reaction of Nltryl Chloride with a Secondary Nltroalkane 2k 1. 2-Nltropropane 11. Sodium 2-Nltropropane c. Reaction of Sodium 2-Nltropropane, Nltryl Chloride and Aluminum Chloride. 27 2. Reaction of Sodium 2-Nltropropane With Mixed Nitric and Sulfuric Acids 28 3.
    [Show full text]
  • Saccharomyces Cerevisiae EZ-Accu Shottm
    General Catalog of Kanto Reagents, Chemicals & Biologicals + Oct. 2021 Saccharomyces cerevisiae EZ-Accu ShotTM store at 2℃-8℃ 49944-78 MB（0699A） ATCC9763 5test JPY46,000 Saccharomyces cerevisiae KWIK-STIKTM store at 2℃-8℃ 49843-14 MB（0534P） ATCC4098 2pack JPY13,500 49843-15 MB（0900P） ATCC9080 2pack JPY13,500 49823-87 MB（0699P） ATCC9763 2pack JPY13,500 49820-65 MB（01066P） ATCC18824 2pack JPY14,500 49825-87 MB（0736P） NCYC79 2pack JPY14,500 Saccharomyces cerevisiae KWIK-STIKTM Plus store at 2℃-8℃ 49842-47 MB（0699X） ATCC9763 5pack JPY45,000 Saccharomyces kudriavzevii KWIK-STIKTM store at 2℃-8℃ 49823-86 MB（0698P） ATCC2601 2pack JPY13,500 Saccharomyces kudriavzevii KWIK-STIKTM Plus store at 2℃-8℃ 49840-76 MB（0698X） ATCC2601 5pack JPY45,000 Salmonella bongori KWIK-STIKTM store at 2℃-8℃ 49843-52 MB（0595P） ATCC43975 2pack JPY16,500 General Catalog of Kanto Reagents, Chemicals & Biologicals + Oct. 2021 Salmonella enterica subsp.arizonae EZ-Accu ShotTM store at 2℃-8℃ 49946-13 MB（0901A） ATCC13314 5test JPY46,000 Salmonella enterica subsp.arizonae KWIK-STIKTM store at 2℃-8℃ 49823-91 MB（0901P） ATCC13314 2pack JPY13,500 Salmonella enterica subsp.diarizonae KWIK-STIKTM store at 2℃-8℃ 49820-33 MB（01054P） ATCC12325 2pack JPY14,500 49844-90 MB（01045P） ATCC29934 2pack JPY14,500 Salmonella enterica subsp.enterica serotype Abony EZ-CFUTM store at 2℃-8℃ 49840-79 MB（0890C） NCTC6017 10test JPY87,000 Salmonella enterica subsp.enterica serotype Abony EZ-CFUTM One Step store at 2℃-8℃ 49842-70 MB（0890Z） NCTC6017 10test JPY86,000 Salmonella enterica subsp.enterica serotype Abony KWIK-STIKTM store at 2℃-8℃ 49825-88 MB（0890P） NCTC6017 2pack JPY11,500 General Catalog of Kanto Reagents, Chemicals & Biologicals + Oct.
    [Show full text]