DOCSLIB.ORG

Asymmetric Synthesis Utilizing Cascade Reactions

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Asymmetric Synthesis Utilizing Cascade Reactions MSc Chemistry Molecular Sciences Literature Thesis _____________________________________________________________________________________ Asymmetric synthesis utilizing cascade reactions Application of cascade reactions in total synthesis of complex natural compounds _____________________________________________________________________________________ _________ By Jurgen van Schaijk, 11958782 February 2021 12 EC Primary examiner: Prof. Dr. Jan van Maarseveen Secondary examiner: --- Van ‘t Hoff Institute for Molecular Sciences Synthetic Organic Chemistry Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis 2 Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis ABSTRACT Total synthesis of natural products can usually become quite a lengthy series of synthetic steps. Although through this method the goal of the project can be reached, the issue is that the lengthy process is not only lengthy but also not atom economic. A partial solution to shorten these lengthy synthetic schemes and increase the atom economy, cascade reactions can be utilized. Cascade reactions, also known as domino or tandem reactions, is a chemical process consisting of at least two subsequent reactions where one transformation only occurs due to the previously formed chemical functionality. Isolation of intermediates is usually not observed, this is due to spontaneous nature of the sequence of reactions. In this literature thesis we cover the different groups of cascade reactions and their applications in natural product synthesis. The cascade reactions can be categorized in the following groups: Nucleophilic-, electrophilic-, oganocatalytic-, pericyclic-, and radical cascades. 3 Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis LIST OF ABBREVIATIONS AcOH acetic acid AIBN azobisisobutyronitrile Boc/Boc2O tert-Butoxycarbonyl/di-tert-butylcarbonate DABCO 1,4-diazabicyclo[2.2. 2]octane DCC N,N′-Dicyclohexylcarbodiimide DCM dichloromethane DDQ 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone DIBAL diisobutylaluminium DMAP 4-dimethylaminopyridine DMF dimethylformamide DMP Dess-Martin periodinane DMSO dimethylsulfoxide DPPA diphenylphosphoryl azide KHMDS potassium bis(trimethylsilyl)amide KI potassium iodide LDA lithium diisopropylamide MOM methoxymethyl Phth phthalimide PPA polyphosphoric acid PTC phase-transfer catalysts Py pyridine TBAF tetra-n-butylamonium fluoride TBDPS tert-butyldiphenylsilyl TBS tert-butyldimethylsilyl TEA triethyl amine TFA trifluoroacetic acid TfOH trifluoromethanesulfonic acid THF tertrahydro furan TMS tetrramethylsilane TMSO trimethylsilyl ether D2-He 4 Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis CONTENTS Abstract ......................................................................................................................................................... 3 List of Abbreviations ...................................................................................................................................... 4 Introduction ................................................................................................................................................... 6 Early work in Cascade reactions ................................................................................................................ 8 Types of cascades ...................................................................................................................................... 9 Nuclephillic / electrophilic cascades ...................................................................................................... 9 Organocatalytic cascades ..................................................................................................................... 10 Radical cascades ................................................................................................................................... 11 Pericyclic cascades ............................................................................................................................... 12 Goals of this thesis....................................................................................................................................... 14 Cascade reactions in asymmetric synthesis ................................................................................................ 15 Chiral auxiliaries ....................................................................................................................................... 15 Cation-mediated cascade reactions ........................................................................................................ 15 Anion-mediate asymmetric cascade reactions ........................................................................................ 23 Pericyclic cascades ................................................................................................................................... 27 Radical cascades ...................................................................................................................................... 32 Conclusion and OUTLOOK ........................................................................................................................... 36 Acknowledgements ..................................................................................................................................... 38 References ................................................................................................................................................... 39 5 Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis INTRODUCTION Development over the past decades in synthetic organic chemistry has influenced the field in fascinating ways. A considerable number of highly selective procedures have come to light which allow for the synthesis of complex molecules with excellent regio-, chemo-, diastereo-, and enantioselectivity.1 Amongst these is an incredible example for the synthesis of palytoxin, which contains 64 stereogenic centers and of which over 1019 different stereoisomers could exist.2 Despite such a great success, society’s image of chemistry has deteriorated, which could be explained by the increasing importance of environmental issues and the negative influence organic chemistry can have on the ecological balance.2 It is no longer only important what we can synthesize, but also how we go about it. Important issues in chemical production are the handling of chemical waste, the search for environmentally friendly/tolerable procedures, preservation of resources, and the increase of efficiency. Solution to these problems are not only important for the environmental concerns, but these also aid in the reduction of production costs. FIGURE 1. STRUCTURE OF PALYTOXIN. 6 Recent Advances in Asymmetric Cascade Reactions: Applications in Polycyclic Natural Product Synthesis Traditional procedures for the synthesis of compounds are usually conducted in a stepwise fashion, forming individual bonds one step at a time. A viable alternative to such a stepwise procedure would be the utilization of cascade type reactions. The utilization of cascade reactions grants organic chemists the ability to synthesize complex structures in one-pot reactions without the necessity to isolate intermediates. Chemical transformations with such an approach offer efficiency, economic benefits and relatively ecologically benign synthesis; a must for every organic chemist.3 The usefulness of cascade reactions is correlated by the number of bonds which are formed in a single sequence (called bond-forming efficiency), the increase in structural complexity, and whether it is suitable for general application.2 Cascade reactions can fall under the banner of “green chemistry”, this is due to the considerable savings involved when a single reaction step carries out several transformations.4 Consideration to follow the guidelines of “green chemistry” will become increasingly important in the future because both chemists and society in general will strive for increasingly more efficient and responsible methods for the management of natural resources. In their review of cascade reactions (2006), Nicolaou et al. wrote: “Target-oriented synthesis provides the ultimate test of reaction design and applicability. The design of cascades to provide specific targeted molecules of considerable structural and stereochemical complexity poses a significant intellectual challenge and can be one of the most impressive activities in natural product synthesis. Cascade reactions therefore contribute immeasurably to both the science and art of total synthesis, bringing not only improved practical efficiency but also enhanced aesthetic appeal to synthetic planning. The recognition of these dual benefits is, of course, by no means an exclusively modern phenomenon. Indeed, cascade reactions (either as designed sequences or serendipitous discoveries) have attracted the attention of organic chemists since the formative years of total synthesis.”4 Tietze has defined a domino/cascade as reaction which involves two or more bond-forming transformations which take place under the same reaction conditions without adding additional reagents or catalysts, and in which the subsequent reactions only result as a consequence of the functionality formation derived from a previous
Load more

Recommended publications
  • Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae)
    Biomolecules 2015, 5, 910-942; doi:10.3390/biom5020910 OPEN ACCESS biomolecules ISSN 2218-273X www.mdpi.com/journal/biomolecules/ Review Endiandric Acid Derivatives and Other Constituents of Plants from the Genera Beilschmiedia and Endiandra (Lauraceae) Bruno Ndjakou Lenta 1,2,*, Jean Rodolphe Chouna 3, Pepin Alango Nkeng-Efouet 3 and Norbert Sewald 2 1 Department of Chemistry, Higher Teacher Training College, University of Yaoundé 1, P.O. Box 47, Yaoundé, Cameroon 2 Organic and Bioorganic Chemistry, Chemistry Department, Bielefeld University, P.O. Box 100131, 33501 Bielefeld, Germany; E-Mail: [email protected] 3 Department of Chemistry, University of Dschang, P.O. Box 67, Dschang, Cameroon; E-Mails:[email protected] (J.R.C.); [email protected] (P.A.N.-E.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +2376-7509-7561. Academic Editor: Jürg Bähler Received: 3 March 2015 / Accepted: 6 May 2015 / Published: 14 May 2015 Abstract: Plants of the Lauraceae family are widely used in traditional medicine and are sources of various classes of secondary metabolites. Two genera of this family, Beilschmiedia and Endiandra, have been the subject of numerous investigations over the past decades because of their application in traditional medicine. They are the only source of bioactive endiandric acid derivatives. Noteworthy is that their biosynthesis contains two consecutive non-enzymatic electrocyclic reactions. Several interesting biological activities for this specific class of secondary metabolites and other constituents of the two genera have been reported, including antimicrobial, enzymes inhibitory and cytotoxic properties. This review compiles information on the structures of the compounds described between January 1960 and March 2015, their biological activities and information on endiandric acid biosynthesis, with 104 references being cited.
    [Show full text]
  • Front Matter
    Towards the Total Synthesis of 1!,25-dihydroxylumisterol A. Simon Partridge Julia Laboratory, Department of Chemistry, Imperial College London, South Kensington Campus, London SW7 2AZ, United Kingdom September 2012 A thesis submitted as partial fulfilment of the requirements for the degree of Doctor of Philosophy, Imperial College London. Abstract This thesis is divided into three chapters. The first chapter provides a brief review on recent work in the application of cascade cyclisations to the total synthesis of natural products. This is followed by a review of the decarboxylative Claisen rearrangement (dCr), a novel variant of the Ireland-Claisen reaction in which tosylacetic esters of allylic alcohols are transformed into homoallylic sulfones using BSA and potassium acetate, and its applications. The second chapter discusses the results of our studies towards the total synthesis of 1!,25-dihydroxylumisterol via a proposed route containing two key steps; a cascade-inspired, Lewis-acid mediated cyclisation to form the steroid B-ring in I, and the dCr reaction of tosylacetic ester IV to give diene III. Successful syntheses, as well as problems encountered along this route will be discussed, as well as the measures taken to adapt the synthesis to circumvent these problems. OH PGO H O OH H H H H H PGO PGO H H HO Ts Ts 1!,25-dihydroxylumisterol I II OH O H + O H O H HO Ts PGO OPG H Ts Ts OPG VI V IV III The third and final chapter contains experimental procedures and characterisation data for the prepared compounds. Declaration I certify that all work in this thesis is solely my own, except where explicitly stated and appropriately referenced.
    [Show full text]
  • Stable Lithium Diisopropylamide and Method of Preparation
    Europaisches Patentamt J European Patent Office Publication number: 0 205 583 Office europeen des brevets B1 EUROPEAN PATENT SPECIFICATION (45) Date of publication of patent specification: 30.01.91 Intel.5: C 07 C 211/65 (3) Application number: 86900522.3 @ Date of filing: 17.12.85 (8) International application number: PCT/US85/02509 ® International publication number: WO 86/03744 03.07.86 Gazette 86/14 STABLE LITHIUM DIISOPROPYLAMIDE AND METHOD OF PREPARATION. (M) Priority: 24.12.84 US 685318 Proprietor: LITHIUM CORPORATION OF AMERICA, INC. Post Office Box 795 Date of publication of application: Bessemer City, NC 28016 (US) 30.12.86 Bulletin 86/52 Inventor: MORRISON, Robert, Charles Publication of the grant of the patent: 1946 Elmwood Drive 30.01.91 Bulletin 91/05 Gastonia, NC 28054 (US) Inventor: HALL, Randy, Winf red Route 4 Box 697 (M) Designated Contracting States: Kings Mountain, NC 28086 (US) AT BE CH DE FR GB IT LI LU NL SE Inventor: RATHMAN, Terry, Lee 3843 Gardner Park Drive Gastonia, NC 28054 (US) References cited: US-A-3197 516 US-A-3 694516 US-A-3388178 US-A-4 006187 Representative: Gore, Peter Manson et al US-A-3446 860 US-A-4399 078 W.P. THOMPSON & CO. Coopers Building Church Street JOURNAL OF ORGANOMETALLIC CHEMISTRY, Liverpool L1 3AB (GB) vol. 4, 1965; GILMAN et al.: "Stabilities of some n-alkyllithium compounds in mixed solvent CO I References cited: 00 systems", pp. 483-487 JOURNAL OF ORGANOMETTALIC CHEMISTRY, m JOURNAL OF AMERICAN CHEMICAL SOCIETY, vol. 29, 1971; HONEYCUTT: "Kinetics of the in vol.
    [Show full text]
  • Safe Handling of Organolithium Compounds in the Laboratory
    FEATURE Safe handling of organolithium compounds in the laboratory Organolithium compounds are extremely useful reagents in organic synthesis and as initiators in anionic polymerizations. These reagents are corrosive, flammable, and in certain cases, pyrophoric. Careful planning prior to execution of the experiment will minimize hazards to personnel and the physical plant. The proper personal protective equipment (PPE) for handling organolithium compounds will be identified. Procedures to minimize contact with air and moisture will be presented. Solutions of organolithium compounds can be safely transferred from the storage bottles to the reaction flask with either a syringe or a cannula. With the utilization of these basic techniques, organolithium compounds can be safely handled in the laboratory. By James A. Schwindeman, oxides (typi®ed by lithium t-butoxide). various classes of organolithium com- Chris J. Woltermann, and These organolithium compounds have pounds, with pKa from 15.2 (lithium Robert J. Letchford found wide utility as reagents for methoxide) to 53 (t-butyllithium).5 organic synthesis in a variety of appli- Fourth, organolithium reagents demon- cations. For example, they can be strate enhanced nucleophilicity com- INTRODUCTION employed as strong bases (alkyl- pared to the corresponding organo- When properly handled, organo- lithiums, aryllithiums, lithium amides magnesium compound. Finally, they lithiums provide unique properties and lithium alkoxides), nucleophiles are convenient, as a variety of organo- that allow for
    [Show full text]
  • Lithium Diisopropylamide: Nonequilibrium Kinetics and Lessons Learned About Rate Limitation Russell F
    Perspective pubs.acs.org/joc Lithium Diisopropylamide: Nonequilibrium Kinetics and Lessons Learned about Rate Limitation Russell F. Algera, Lekha Gupta, Alexander C. Hoepker, Jun Liang, Yun Ma, Kanwal J. Singh, and David B. Collum* Department of Chemistry and Chemical Biology Baker Laboratory, Cornell University, Ithaca, New York 14853-1301, United States *S Supporting Information ABSTRACT: The kinetics of lithium diisopropylamide (LDA) in tetrahydrofuran under nonequilibrium conditions are reviewed. These conditions correspond to a class of substrates in which the rates of LDA aggregation and solvation events are comparable to the rates at which various fleeting intermediates react with substrate. Substrates displaying these reactivities, by coincidence, happen to be those that react at tractable rates on laboratory time scales at −78 °C. In this strange region of nonlimiting behavior, rate-limiting steps are often poorly defined, sometimes involve deaggregation, and at other times include reaction with substrate. Changes in conditions routinely cause shifts in the rate-limiting steps, and autocatalysis is prevalent and can be acute. The studies are described in three distinct portions: (1) methods and strategies used to deconvolute complex reaction pathways, (2) the resulting conclusions about organolithium reaction mechanisms, and (3) perspectives on the concept of rate limitation reinforced by studies of LDA in tetrahydrofuran at −78 °C under nonequilibrium conditions. ithium diisopropylamide (LDA), a highly reactive and at −78 °Cconditions that are of singular importance in L selective Brønsted base, stands among the most prominent organic synthesisoccur at nearly the rates at which the reagents in organic synthesis.1 A survey of 500 total syntheses aggregates in Scheme 1 exchange.
    [Show full text]
  • Development of an Assay for a Diels-Alderase Enzyme
    Development of an Assay for a Diels-Alderase Enzyme A Thesis submitted in part fulfilment of the requirements of the degree of Doctor of Philosophy Graeme Douglas McAllister Department of Chemistry University of Glasgow Glasgow G12 8QQ February 2000 ©Graeme D. McAllister ProQuest Number: 13818648 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13818648 Published by ProQuest LLC(2018). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 Dedicated to iny family "Do they give Nobel prizes for attempted chemistry? Do they!?" from 'The Simpsons' by Matt Groening Acknowledgements First of all my sincerest thanks go to my supervisor, Dr Richard Hartley, for his expert guidance over the last 3 years. I would also like to thank Dr Mike Dawson and Dr Andy Knaggs of GlaxoWellcome for their supervision and ideas in the biological areas of this project, and for helping a chemist adjust to life in a biology lab! Dr Chris Brett of the University of Glasgow and Mrs Jyoti Vithlani of GlaxoWellcome deserve a mention for all their expertise in the growing of cell cultures and for helping me in the feeding studies.
    [Show full text]
  • Isolation and Identification of Cyclic Polyketides From
    ISOLATION AND IDENTIFICATION OF CYCLIC POLYKETIDES FROM ENDIANDRA KINGIANA GAMBLE (LAURACEAE), AS BCL-XL/BAK AND MCL-1/BID DUAL INHIBITORS, AND APPROACHES TOWARD THE SYNTHESIS OF KINGIANINS Mohamad Nurul Azmi Mohamad Taib, Yvan Six, Marc Litaudon, Khalijah Awang To cite this version: Mohamad Nurul Azmi Mohamad Taib, Yvan Six, Marc Litaudon, Khalijah Awang. ISOLATION AND IDENTIFICATION OF CYCLIC POLYKETIDES FROM ENDIANDRA KINGIANA GAMBLE (LAURACEAE), AS BCL-XL/BAK AND MCL-1/BID DUAL INHIBITORS, AND APPROACHES TOWARD THE SYNTHESIS OF KINGIANINS . Chemical Sciences. Ecole Doctorale Polytechnique; Laboratoires de Synthase Organique (LSO), 2015. English. tel-01260359 HAL Id: tel-01260359 https://pastel.archives-ouvertes.fr/tel-01260359 Submitted on 22 Jan 2016 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. ISOLATION AND IDENTIFICATION OF CYCLIC POLYKETIDES FROM ENDIANDRA KINGIANA GAMBLE (LAURACEAE), AS BCL-XL/BAK AND MCL-1/BID DUAL INHIBITORS, AND APPROACHES TOWARD THE SYNTHESIS OF KINGIANINS MOHAMAD NURUL AZMI BIN MOHAMAD TAIB FACULTY OF SCIENCE UNIVERSITY
    [Show full text]
  • Lithium Diisopropylamide, 2M Solution in THF/N-Heptane/Ethylbenzene
    Material Safety Data Sheet Creation Date 01-Apr-2009 Revision Date 01-Apr-2009 Revision Number 1 1. PRODUCT AND COMPANY IDENTIFICATION Product Name Lithium diisopropylamide, 2M solution in THF/n-heptane/ethylbenzene Cat No. AC268830000, AC268831000, AC268838000 Synonyms LDA.THF complex Recommended Use Laboratory chemicals Company Entity / Business Name Emergency Telephone Number Fisher Scientific Acros Organics For information in the US, call: 800-ACROS-01 One Reagent Lane One Reagent Lane For information in Europe, call: +32 14 57 52 Fair Lawn, NJ 07410 Fair Lawn, NJ 07410 11 Tel: (201) 796-7100 Emergency Number, Europe: +32 14 57 52 99 Emergency Number, US: 201-796-7100 CHEMTREC Phone Number, US: 800-424- 9300 CHEMTREC Phone Number, Europe: 703- 527-3887 2. HAZARDS IDENTIFICATION DANGER! Emergency Overview Flammable liquid and vapor. May form explosive peroxides. Water reactive. Causes burns by all exposure routes. Vapors may cause drowsiness and dizziness. Aspiration hazard if swallowed - can enter lungs and cause damage. Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment. Appearance Orange. Physical State Liquid. Odor pungent. Target Organs Skin, Respiratory system, Eyes, Gastrointestinal tract (GI), Central nervous system (CNS), Liver, Kidney, spleen, Blood Potential Health Effects Acute Effects _____________________________________________________________________________________________ Page 1 / 11 Thermo Fisher Scientific - Lithium diisopropylamide, Revision Date 01-Apr-2009 2M solution in THF/n-heptane/ethylbenzene _____________________________________________________________________________________________ Principle Routes of Exposure Eyes Causes burns. Skin Causes burns. May be harmful in contact with skin. Inhalation Causes burns. May be harmful if inhaled. Inhalation may cause central nervous system effects. Ingestion Causes burns.
    [Show full text]
  • Organolithium Compounds Brochure
    Contents I. Introduction . .4 II. Organolithium compounds, properties & structures . .5 III. Reactions of organolithium compounds . .6 a. Metallation . .6 b. Ortho-metallation . .7 c. Nucleophilic addition and substitution . .7 d. Halogen-Metal exchange . .8 e. Transmetallation . .9 f. Anionic Polymerisation . .9 IV. Named organic reactions with organolithium compounds . .10 a. [1,2] and [2,3]-Wittig rearrangement . .10 b. Shapiro Olefination . .10 c. Peterson Olefination . .10 d. Ramberg-Bäcklund-Reaction . .10 e. Parham Cyclization . .11 V. Indicators for the titration of organolithium compounds . .12 VI. Organolithium compounds available at Acros Organics . .14 Dry-solvents . .15 3 I. Introduction Organometallic compounds are amongst the most often used reagents in organic synthesis. The earliest organometallic compound was already discovered in the early 19th cen- tury (“Zeise’s salt”; a zinc-olefin complex was first reported in 1827!) and first exam- ples of synthetic organometallic chemistry are the organozinc-compounds, discovered by Edward Frankland in 1849, the organo-magnesium compounds discovered by Victor Grignard and his teacher Philippe Barbier in 1901 and the organolithium com- pounds, discovered by Wilhelm Schlenk in 1917(1) But only since the 1950th, based on the pioneering work of Georg Wittig and Henry Gilman, organometallic reagents became a routinely used tool in the syn- thetic organic laboratory. A very early but still invaluable application of organometallic reagents is the olefin- polymerisation with the so-called
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2014/0084224 A1 Rittmeyer Et Al
    US 20140O84224A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2014/0084224 A1 Rittmeyer et al. (43) Pub. Date: Mar. 27, 2014 (54) PROCESS FOR PREPARING LITHIUM (30) Foreign Application Priority Data SULFIDE May 27, 2011 (DE) ...................... 10 2011 O76 572.7 (75) Inventors: Peter Rittmeyer, Sulzbach/Taunus (DE): Publication Classification Ulrich Wietelmann, Friedrichsdorf (DE); Uwe Lischka, Frankfurt am Main (51) Int. Cl. Bernhard Figer, Frankfurt am Main 52) U.S. C. (DE), Armin Stoll, Hemsbach (DE): (52) CPC ...................................... COIB 17/22 (2013.01) Dirk Dawidowski, Friedberg (DE) USPC ...................... 252/519.4; 423/566.2:423/511 (73) Assignee: CHEMETALL GMBH, Frankfurt am (57) ABSTRACT Main (DE) The invention relates to a novel process for preparing lithium sulfide and to the use thereof, wherein a reaction of lithium (21) Appl. No.: 14/119,980 containing strong bases with hydrogen Sulfide is undertaken in an aprotic organic solvent within the temperature range (22) PCT Filed: May 29, 2012 from -20 to 120° C. under inert conditions. The lithium Sulfide obtained by the process is used as a positive material (86). PCT No.: PCT/EP2012/06OO14 in a galvanic element or for the synthesis of Li ion-conductive S371 (c)(1), Solids, especially for the synthesis of glasses, glass ceramics (2), (4) Date: Nov. 25, 2013 or crystalline products. US 2014/0084224 A1 Mar. 27, 2014 PROCESS FOR PREPARING LITHIUM alkylene, lithium arylene, and lithium amides, and react SULFIDE according to the following equations: 0001. The invention relates to a novel method for prepar ing lithium sulfide, and use thereof.
    [Show full text]
  • Stable Lithium Amides and Reagent Compositions Thereof
    Europaisches Patentamt J) European Patent Office © Publication number: 0 406 1 97 A2 Office europeen des brevets EUROPEAN PATENT APPLICATION C07C C07C © Application number: 90850238.8 © int. CIA 211/06, 211/07, C07C 211/09, C07C 209/00 © Date of filing: 15.06.90 © Priority: 30.06.89 US 374740 © Applicant: CYPRUS FOOTE MINERAL 11.10.89 US 419966 COMPANY Suite 301, 301 Lindenwood Drive © Date of publication of application: Malvern, Pennsylvania 1 9355-1 70(US) 02.01.91 Bulletin 91/01 @ Inventor: Smith, W. Novis, Jr. © Designated Contracting States: 412 South Perth Street AT BE CH DE ES FR GB IT LI NL SE Philadelphia Pa 19147(US) © Representative: Onn, Thorsten et al AB STOCKHOLMS PATENTBYRA Box 3129 S-103 62 Stockholm(SE) © Stable lithium amides and reagent compositions thereof. © A method for preparing lithium amides in a monocyclic aromatic solvent and the reagent compositions formed thereby. CO o HI Xerox Copy Centre EP 0 406 197 A2 STABLE LITHIUM AMIDES AND REAGENT COMPOSITIONS THEREOF BACKGROUND OF THE INVENTION The present invention relates to stable lithium amides and reagent compositions which are free of 5 tetrahydrofuran and ethers. More particularly, the invention concerns the preparation of lithium amides and to reagent compositions thereof containing increased concentrations of the lithium amide in solution and capable of producing increased yields in subsequent reactions. Lithium amides, for example, lithium diisopropopylamide are widely used as a reagents in the preparation of Pharmaceuticals and specialty chemicals. Lithium amides are particularly useful for the w preparation of lithium acetylide compounds which are used to form acetylenic substituted organic com- pounds such as steroid and fragrance intermediates.
    [Show full text]
  • Lithium Diisopropylamide
    Lithium diisopropylamide sc-252958 Material Safety Data Sheet Hazard Alert Code Key: EXTREME HIGH MODERATE LOW Section 1 - CHEMICAL PRODUCT AND COMPANY IDENTIFICATION PRODUCT NAME Lithium diisopropylamide STATEMENT OF HAZARDOUS NATURE CONSIDERED A HAZARDOUS SUBSTANCE ACCORDING TO OSHA 29 CFR 1910.1200. NFPA FLAMMABILITY3 HEALTH3 HAZARD INSTABILITY2 W SUPPLIER Company: Santa Cruz Biotechnology, Inc. Address: 2145 Delaware Ave Santa Cruz, CA 95060 Telephone: 800.457.3801 or 831.457.3800 Emergency Tel: CHEMWATCH: From within the US and Canada: 877-715-9305 Emergency Tel: From outside the US and Canada: +800 2436 2255 (1-800-CHEMCALL) or call +613 9573 3112 PRODUCT USE Hindered non-nucleophilic strong base used for the generation of carbanions. SYNONYMS C6-H14-Li-N, [(CH3)2CH]2NLi, LDA, lithiodiisopropylamine Section 2 - HAZARDS IDENTIFICATION CANADIAN WHMIS SYMBOLS EMERGENCY OVERVIEW RISK Spontaneously flammable in air. Causes burns. Risk of serious damage to eyes. Reacts violently with water liberating extremely flammable gases. Highly flammable. 1 of 13 May cause fire. POTENTIAL HEALTH EFFECTS ACUTE HEALTH EFFECTS SWALLOWED • The material can produce chemical burns within the oral cavity and gastrointestinal tract following ingestion. • Accidental ingestion of the material may be damaging to the health of the individual. • Lithium, in large doses, can cause dizziness and weakness. If a low salt diet is in place, kidney damage can result. There may be dehydration, weight loss, skin effects and thyroid disturbances. Central nervous system effects include slurred speech, blurred vision, numbness, inco-ordination and convulsions. Repeated exposure can cause diarrhea, vomiting, tremor, muscle jerks and very brisk reflexes. • Pyrophoric compounds may produce gastrointestinal damage resulting fromlocal generation of heat.
    [Show full text]