DOCSLIB.ORG

Three Fatal Sodium Azide Poisonings*

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Three Fatal Sodium Azide Poisonings* Toxicology Experience Report Med. Toxicol. Adverse Drug Exp. 4: 219-227 (1989) oI I 3-5244/89/0005-02 I9/S04.50/0 © ADIS Press Limited All rights reserved. Three Fatal Sodium Azide Poisonings* Wendy Klein-Schwartz,l Richard L. Gorman, 1 Gary M. Oderda,l Brian P. Massaro, 2 Thomas L. Kurt 3 and James C. Garriott 4 I Maryland Poison Center, University of Maryland School of Pharmacy and School of Medicine, Baltimore, Maryland, USA 2 Frederick Memorial Hospital, Frederick, Maryland, USA 3 North Central Texas Poison Center, Parkland Memorial Hospital, Dallas, Texas, USA 4 Office of the Medical Examiner, San Antonio, Texas, USA Summary We report 3 cases and review the published literature on sodium azide ingestion. A 38-year-old man intentionally ingested 2 tablespoonsful of sodium azide in water and developed seizures. coma. hypotension and fatal ventricular arrhythmias within 2 hours. A 33-year-old male ingested an unknown quantity of sodium azide. In the emergency department he was unconscious and underwent immediate intubation and gastric lavage. Nitrite therapy was instituted without improvement. He remained acidotic despite bicarb­ onate therapy and developed hypotension which was unresponsive to pressor agents. He died approximately 8 hours after admission despite resuscitative efforts. A 52-year-old male ingested 1.5 to 2g of sodium azide and survived for 40 hours. Nitrite therapy was ineffective. The role of sodium nitrite in treating sodium azide toxicity by producing methaemo­ globin which complexes with azide is discussed. Sodium azide is a highly toxic chemical which ported previously. In 2 of the fatal cases the amount is lethal in small amounts. It is used both in the ingested was estimated to be 10 to 20g (Abrams et explosive industry to prepare heavy metal azides al. 1987; Albertson et al. 1986). Clinical manifes­ for shell detonators and as a common preservative tations include neurological, cardiovascular and in laboratory reagents. Sodium azide is a direct va­ pulmonary toxicity. We report 3 additional fatal sodilator and was used to treat hypertension in the intentional ingestions of sodium azide. 1950s. Sodium azide interferes with mitochondrial phosphorylation and inhibits cytochrome oxidase Case Reports and other oxidative enzymes. 13 cases of sodium azide ingestion, including 4 deaths, have been re- Case I A 38-year-old man intentionally ingested 2 tablespoonsful of sodium azide diluted in water * Presented in part at the annual meeting of the American Association of Poison Control Centers, Santa Fe, New Mexico, (55g, estimated based on density). In the ambul­ September 28, 1986. ance 30 minutes after ingestion he had a heart rate Fatal Azide Poisonings 220 of 80 beats per minute, blood pressure of 110/ ation revealed a pIa_sma bicarbonate concentration 80mm Hg, respiratory rate of 30 per minute. The of 8 mmol/L as the only abnormality with normal patient had a generalised tonic clonic seizure and complete blood count, prothrombin time, partial his level of consciousness progressively deterio­ thromboplastin time and other electrolytes. Sali­ rated. On arrival in the emergency department I cylate level was 4.1 mg/dl (0.30 mmol/L), but blood hour after ingestion, he was comatose and unres­ and urine were negative for common toxins. The ponsive with heart rate of 160 beats per minute, methaemoglobin level approximately I hour after blood pressure of 130/80mm Hg, respiratory rate administration of sodium nitrite was below 0.5 g/ of 20 per minute. Naloxone was administered dl (within normal physiological range). without response. He was immediately intubated, On admission to the intensive care unit, the placed on 100% oxygen and gastric lavage per­ patient was comatose with corneal reflexes present. formed. 20 minutes after arrival in the emergency The pupils remained fixed and dilated. Lungs were department he developed ventricular fibrillation clear and he was breathing spontaneously on 100% and hypotension (blood pressure of 84/50mm Hg). oxygen by nasal cannula. Arterial blood gases re­ He was unresponsive to resuscitative efforts in­ vealed pH = 7.34, pC02 = 11.4mm Hg, p02 = cluding intravenous dopamine and was pro­ I 52mm Hg, base excess = -18. His neurological nounced dead 1.5 hours after ingestion. and cardiovascular condition deteriorated rapidly and he became unresponsive to pain with loss of Case 2 corneal and deep tendon reflexes. At 3 hours after A 33-year-old male coworker of case I inten­ admission, his blood pressure dropped to 80/ tionally ingested an unknown quantity of sodium 40mm Hg and dopamine was started. He remained azide approximately 2 months later. He told his profoundly hypotensive (60/30mm Hg) and oli­ wife of the ingestion and then collapsed. En route guric despite increasing doses of dopamine. Pre­ to the emergency department he became uncon­ mature ventricular contractions developed which scious with muscle rigidity, a heart rate of 120 beats responded to lignocaine (lidocaine). Acidosis (pH per minute, blood pressure of 90/60mm Hg and = 7.2) persisted despite continued administration respiratory rate of 20 per minute. On arrival, he of sodium bicarbonate. At 5 hours after admission was unconscious and diaphoretic. His pupils were he developed respiratory depression and was placed fixed and dilated. Lungs were clear. Cardiac exam­ on a ventilator; lungs remained clear. Eight hours ination was remarkable only for tachycardia. after admission he became bradycardic (30 beats/ Muscles were flaccid with fasciculations. Electro­ min) which briefly responded to atropine and sod­ cardiogram showed sinus tachycardia with non­ ium bicarbonate. He became profoundly brady­ specific T -wave changes, and a chest x-ray was un­ cardic I minute later and did not respond to ad­ remarkable. The patient was immediately intubated ditional atropine or adrenaline (epinephrine), and and started on 100% oxygen. Orogastric lavage was he was pronounced dead shortly thereafter. performed which recovered a large amount of flaky white material. Later, nasogastric tube drainage was Case 3 grossly bloody. Intravenous therapy was initiated A 52-year-old white man ingested between 1.2 with Ringers lactate and the patient received 300 and 2g of sodium azide in a suicide attempt. The mmol of sodium bicarbonate. Nitrite therapy to in­ man held a doctorate in pharmacology and was un­ duce methaemoglobinaemia was initiated with the der severe psychological stress at the time of the cyanide antidote kit: amyl nitrite (0.3ml) by in­ ingestion. He had access to sodium azide at his halation for 15 seconds, followed by 300mg of sod­ place of employment in the hospital. On arrival in ium nitrite intravenously. The patient also re­ the emergency department about 3 hours post­ ceived 12.5g of sodium thiosulphate. No ingestion he was alert and oriented, moving all ex­ improvement was noted. Initial laboratory evalu- tremities and ambulating well. 10 minutes after ar- Fatal Azide Poisonings 221 rival he experienced a generalised tonic clonic treatments with the cyanide antidote kit with 5- seizure which was controlled with intravenous di­ minute infusions of 300mg sodium nitrite followed azepam. by 3-minute infusions of 12.5g of sodium thiosul­ He was admitted to a medical intensive care unit phate. An autopsy showed bilateral pulmonary with a diagnosis of acute sodium azide ingestion. oedema and congestion, brain swelling and ery­ His condition upon admission was described as thema of the gastric lining but no other cause of flaccid with no response to deep pain. Pupils were death. The conclusion of the medical examiner was 3mm and unreactive. He was intubated, a venous that the death was a result of acute intoxication line was placed into a central vein and an indwell­ with sodium azide. ing urethral catheter was placed. Initial laboratory The maximum methaemoglobin level was 16.1 % evaluation revealed a plasma bicarbonate concen­ which was obtained 1 hour after the second treat­ tration of 8 mmol/L with normal prothrombin ment. The methaemoglobin level ranged from 9 to time, partial thromboplastin time and other elec­ 14% for the other courses of therapy. trolytes. After consultation with the Poison Center, treatment with the cyanide antidote kit (sodium Discussion nitrite and sodium thiosulphate) was initiated. Plasma cyanide ion concentration obtained at this Sodium azide is a neutral, stable, white crystal­ time was 1.6 mg/L; the minimum toxic concentra­ line solid which is hydrolysed in aqueous solutions tion is 0.5 mgfL and the lethal concentration is 2.0 to release hydrazoic acid (Reinhardt & Brittelli mg/L. The blood and urine were negative for com­ 1981). It is rapidly absorbed from the gastrointes­ mon toxic substances. The contents of the vial from tinal tract, skin and respiratory tract. Sodium azide which he ingested the powder were analysed and is highly toxic, with an LDso of 27 mg/kg in mice were negative for cyanide. The vial was not ana­ (Christensen & Luginbyhl 1974). Toxicity results lysed for sodium azide. During the first 12 hours, from inhalation of the gas (hydrazoic acid) or sodium nitrite 300mg and sodium thiosulphate ingestion of the sodium salt. Ingestion produces 12.5g were administered intravenously 3 times. neurological, cardiovascular and pulmonary tox­ Seven hours after admission, the patient was de­ icity. Neurological symptoms include headache, scribed as responsive to pain, making purposeful restlessness, faintness, muscle weakness, hypo- or movements and responding to commands. Plasma areflexia, convulsions, coma and respiratory fail­ cyanide ion concentration 12 and 18 hours after ure. The cardiovascular effects include profound admission were 1.7 mg/L and 0.6 mg/L, respec­ hypotension and tachycardia. tively. 24 hours after admission the patient was re­ The severity of the poisoning is dose dependent. sponsive and 'mouthed' around his endotracheal Table I summarises 13 previously reported cases tube that he had taken sodium azide and was aware and the 3 cases reported herein.
Load more

Recommended publications
  • Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules
    ACCOUNT 21 Application of Organic Azides for the Synthesis of Nitrogen-Containing Molecules Shunsuke Chiba* Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore Fax +6567911961; E-mail: [email protected] Received 31 May 2012 Organic azides possess diverse chemical reactivities.4 Abstract: In this account, recent advances made on the reactions of several types of organic azides, such as vinyl azides, cyclic 2-azido Owing to their 1,3-dipole character, they undergo [3+2] alcohols, a-azido carbonyl compounds, towards the synthesis of cycloaddition with unsaturated bonds, such as those in nitrogen-containing molecules are described. alkynes and alkenes as well as carbonitriles (Scheme 1, part a).5 Organic azides can also be regarded as nitrene 1 Introduction equivalents (Scheme 1, part b).6 Accordingly, their reac- 2 Chemistry of Vinyl Azides tions with nucleophilic anions, electrophilic cations, and 2.1 Thermal [3+2]-Annulation of Vinyl Azides with 1,3-Dicar- radicals can formally provide the corresponding nitrogen bonyl Compounds 2.2 Manganese(III)-Catalyzed Formal [3+2]-Annulation with anions, cations, and radicals, respectively, forming a new 1,3-Dicarbonyl Compounds bond with the internal azido nitrogen and releasing molec- 2.3 Manganese(III)-Mediated/Catalyzed Formal [3+3]-Annu- ular nitrogen. Moreover, the generation of anions, cations, lation with Cyclopropanols and radicals at the a-position to the azido moiety can re- 2.4 Synthesis of Isoquinolines from a-Aryl-Substituted Vinyl sult in rapid denitrogenation to deliver the corresponding Azides and Internal Alkynes by Rhodium–Copper Bimetal- iminyl species, which can be used in further synthetic lic Cooperation transformations (i.e., carbon–nitrogen bond formation).
    [Show full text]
  • Safe Handling of Sodium Azide (SAZ)
    Safe Handling of Sodium Azide (SAZ) 1,2 Sodium azide (SAZ, CAS# 26628-22-8) is a white crystalline solid [molecular formula of (NaN3)] used in organic synthesis and also as a well-known preservative at low concentrations in molecular biology reagents. Azide chemistry3,4 offers an effective means to synthesize a range of nitrogen-containing compounds with a wide variety of functional groups. But SAZ poses some significant risks. It is highly toxic and can react to form potentially explosive compounds. Azide reagents and intermediates react with some metals5, strong acids, and certain chlorinated solvents6 and this needs to be considered when using SAZ or when developing routes that involve azide-containing intermediates. Health Hazards & Physical Hazards of SAZ Hazard Statements Fatal if swallowed or in contact with skin. Very toxic to aquatic life with long lasting effects. Health Hazards: SAZ is highly toxic when ingested orally or absorbed through the skin. Azides form strong complexes with hemoglobin, and consequently block oxygen transport in the blood. They are more harmful to the heart and the brain than to other organs, because the heart and the brain use a lot of oxygen. Symptoms of exposure include headache, dizziness, nausea and vomiting, rapid breathing and heart rate, and skin burns and blisters (direct skin contact) and in the case of serious overexposure, convulsions and death. It will also react with acids to form hydrazoic acid (HN3). Unlike sodium azide, which is a crystalline solid, hydrazoic acid is a low-boiling, volatile, liquid. Hydrazoic acid is also highly toxic and its volatility makes it more readily inhaled causing lung irritation and potentially bronchitis and lung edema.
    [Show full text]
  • Soluble Guanylate Cyclase B1-Subunit Expression Is Increased in Mononuclear Cells from Patients with Erectile Dysfunction
    International Journal of Impotence Research (2006) 18, 432–437 & 2006 Nature Publishing Group All rights reserved 0955-9930/06 $30.00 www.nature.com/ijir ORIGINAL ARTICLE Soluble guanylate cyclase b1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction PJ Mateos-Ca´ceres1, J Garcia-Cardoso2, L Lapuente1, JJ Zamorano-Leo´n1, D Sacrista´n1, TP de Prada1, J Calahorra2, C Macaya1, R Vela-Navarrete2 and AJ Lo´pez-Farre´1 1Cardiovascular Research Unit, Cardiovascular Institute, Hospital Clı´nico San Carlos, Madrid, Spain and 2Urology Department, Fundacio´n Jime´nez Diaz, Madrid, Spain The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) b1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC b1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC b1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.
    [Show full text]
  • Synthesis and Consecutive Reactions of Α-Azido Ketones: a Review
    Molecules 2015, 20, 14699-14745; doi:10.3390/molecules200814699 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Review Synthesis and Consecutive Reactions of α-Azido Ketones: A Review Sadia Faiz 1,†, Ameer Fawad Zahoor 1,*, Nasir Rasool 1,†, Muhammad Yousaf 1,†, Asim Mansha 1,†, Muhammad Zia-Ul-Haq 2,† and Hawa Z. E. Jaafar 3,* 1 Department of Chemistry, Government College University Faisalabad, Faisalabad-38000, Pakistan, E-Mails: [email protected] (S.F.); [email protected] (N.R.); [email protected] (M.Y.); [email protected] (A.M.) 2 Office of Research, Innovation and Commercialization, Lahore College for Women University, Lahore-54600, Pakistan; E-Mail: [email protected] 3 Department of Crop Science, Faculty of Agriculture, Universiti Putra Malaysia, Serdang-43400, Selangor, Malaysia † These authors contributed equally to this work. * Authors to whom correspondence should be addressed; E-Mails: [email protected] (A.F.Z.); [email protected] (H.Z.E.J.); Tel.: +92-333-6729186 (A.F.Z.); Fax: +92-41-9201032 (A.F.Z.). Academic Editors: Richard A. Bunce, Philippe Belmont and Wim Dehaen Received: 20 April 2015 / Accepted: 3 June 2015 / Published: 13 August 2015 Abstract: This review paper covers the major synthetic approaches attempted towards the synthesis of α-azido ketones, as well as the synthetic applications/consecutive reactions of α-azido ketones. Keywords: α-azido ketones; synthetic applications; heterocycles; click reactions; drugs; azides 1. Introduction α-Azido ketones are very versatile and valuable synthetic intermediates, known for their wide variety of applications, such as in amine, imine, oxazole, pyrazole, triazole, pyrimidine, pyrazine, and amide alkaloid formation, etc.
    [Show full text]
  • Aziridination of Alkenes Promoted by Iron Or Ruthenium Complexes
    Aziridination of Alkenes Promoted by Iron or Ruthenium Complexes Caterina Damiano, Daniela Intrieri and Emma Gallo* Department of Chemistry, University of Milan, Via C. Golgi 19, 20133 Milan (Italy). E-mail address: [email protected]. Keywords: Aziridines, Nitrene reagents, Alkenes, Homogenous catalysis, Iron, Ruthenium. Abstract Molecules containing an aziridine functional group are a versatile class of organic synthons due to the presence of a strained three member, which can be easily involved in ring-opening reactions and the aziridine functionality often show interesting pharmaceutical and/or biological behaviours. For these reasons, the scientific community is constantly interested in developing efficient procedures to introduce an aziridine moiety into organic skeletons and the one-pot reaction of an alkene double bond with a nitrene [NR] source is a powerful synthetic strategy. Herein we describe the catalytic activity of iron or ruthenium complexes in promoting the reaction stated above by stressing the potential and limits of each synthetic protocol. 1. Introduction Aziridines, the smallest N-heterocycle compounds, have attracted considerable attention in the last few decades due to their many applications in biological and synthetic chemistry [1]. The aziridine functionality is often responsible for the activity of biologically active species (such as antitumor compounds, antibiotics and enzyme inhibitors) and aziridine containing molecules [2] are also useful building blocks in the synthesis of fine chemicals and pharmaceuticals [3-6]. The striking chemical properties of aziridines are due to the energy associated to the strained three- membered ring [7], which renders them very active and versatile starting materials for the synthesis of several useful molecules such as amines, amino acids, β-lactams, polymers and α-amido ketones [8, 9].
    [Show full text]
  • Nitric Oxide Activates Guanylate Cyclase and Increases Guanosine 3':5'
    Proc. Natl. Acad. Sci. USA Vol. 74, No. 8, pp. 3203-3207, August 1977 Biochemistry Nitric oxide activates guanylate cyclase and increases guanosine 3':5'-cyclic monophosphate levels in various tissue preparations (nitro compounds/adenosine 3':5'-cyclic monophosphate/sodium nitroprusside/sodium azide/nitrogen oxides) WILLIAM P. ARNOLD, CHANDRA K. MITTAL, SHOJI KATSUKI, AND FERID MURAD Division of Clinical Pharmacology, Departments of Medicine, Pharmacology, and Anesthesiology, University of Virginia, Charlottesville, Virginia 22903 Communicated by Alfred Gilman, May 16, 1977 ABSTRACT Nitric oxide gas (NO) increased guanylate cy- tigation of this activation. NO activated all crude and partially clase [GTP pyrophosphate-yase (cyclizing), EC 4.6.1.21 activity purified guanylate cyclase preparations examined. It also in- in soluble and particulate preparations from various tissues. The effect was dose-dependent and was observed with all tissue creased cyclic GMP but not adenosine 3':5'-cyclic monophos- preparations examined. The extent of activation was variable phate (cyclic AMP) levels in incubations of minces from various among different tissue preparations and was greatest (19- to rat tissues. 33-fold) with supernatant fractions of homogenates from liver, lung, tracheal smooth muscle, heart, kidney, cerebral cortex, and MATERIALS AND METHODS cerebellum. Smaller effects (5- to 14-fold) were observed with supernatant fractions from skeletal muscle, spleen, intestinal Male Sprague-Dawley rats weighing 150-250 g were decapi- muscle, adrenal, and epididymal fat. Activation was also ob- tated. Tissues were rapidly removed, placed in cold 0.-25 M served with partially purified preparations of guanylate cyclase. sucrose/10 mM Tris-HCl buffer (pH 7.6), and homogenized Activation of rat liver supernatant preparations was augmented in nine volumes of this solution by using a glass homogenizer slightly with reducing agents, decreased with some oxidizing and Teflon pestle at 2-4°.
    [Show full text]
  • Robert Burns Woodward
    The Life and Achievements of Robert Burns Woodward Long Literature Seminar July 13, 2009 Erika A. Crane “The structure known, but not yet accessible by synthesis, is to the chemist what the unclimbed mountain, the uncharted sea, the untilled field, the unreached planet, are to other men. The achievement of the objective in itself cannot but thrill all chemists, who even before they know the details of the journey can apprehend from their own experience the joys and elations, the disappointments and false hopes, the obstacles overcome, the frustrations subdued, which they experienced who traversed a road to the goal. The unique challenge which chemical synthesis provides for the creative imagination and the skilled hand ensures that it will endure as long as men write books, paint pictures, and fashion things which are beautiful, or practical, or both.” “Art and Science in the Synthesis of Organic Compounds: Retrospect and Prospect,” in Pointers and Pathways in Research (Bombay:CIBA of India, 1963). Robert Burns Woodward • Graduated from MIT with his Ph.D. in chemistry at the age of 20 Woodward taught by example and captivated • A tenured professor at Harvard by the age of 29 the young... “Woodward largely taught principles and values. He showed us by • Published 196 papers before his death at age example and precept that if anything is worth 62 doing, it should be done intelligently, intensely • Received 24 honorary degrees and passionately.” • Received 26 medals & awards including the -Daniel Kemp National Medal of Science in 1964, the Nobel Prize in 1965, and he was one of the first recipients of the Arthur C.
    [Show full text]
  • Fabricating Water Dispersible Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications Through Ligand Exchange and Direct Conjugation
    Nanomaterials 2016, 6, 100; doi:nano6060100 S1 of S10 Supplementary Materials: Fabricating Water Dispersible Superparamagnetic Iron Oxide Nanoparticles for Biomedical Applications through Ligand Exchange and Direct Conjugation Tina Lam, Pramod K. Avti, Philippe Pouliot, Foued Maafi, Jean-Claude Tardif, Éric Rhéaume, Frédéric Lesage and Ashok Kakkar Experimental The following compounds were purchased and used as received; tetraethylene glycol, tetraethylene glycol monomethyl ether, p-toluene sulfonyl chloride (tosyl chloride), methane sulfonyl chloride (mesyl chloride), sodium hydroxide, lithium aluminium hydride (LiAlH4), 4- dimethylaminopyridine (DMAP), triethylamine, diethyl amine, sodium azide, tetrabutylammonium iodide, sodium ascorbate (Na Ascorbate), copper(II) sulphate hexahydrate, borane-THF, bis(triphenylphosphine) palladium(II) dichloride, 1-bromo-4-iodo benzene, disodium ethylenediamine tetraacetate (EDTA), iron(II) chloride tetrahydrate (FeCl2·4H2O), iron (III) chloride hexahydrate (FeCl3·6H2O), and oleic acid from Sigma Aldrich (St. Louis, MO, USA), triisopropylsilyl acetylene and trimethylsilyl acetylene from Oakwoods Chemicals (Estill, SC, USA), 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide from Chem Impex International (Wood Dale, IL, USA), and Iron standard # 13830 from Alfa Aesar (Haverhill, MA, USA). Polyvinylidene Fluoride (PVDF) Syringe filters of 17 mm diameter and pore size 0.45 μm were purchased from Sterlitech (Kent, WA, USA). The solvents triethylamine, diethylamine, tetrahydrofuran, acetic acid, acetic anhydride, acetone, chloroform, dichloromethane, benzene, methanol and toluene were purchased from Fisher scientific and ACP Chemicals and used as received. Solvents were obtained from drying columns and purged under N2 prior to use. Milli-Q Ultrapure water was doubly distilled by reverse osmosis though a Millipore RiOS8, followed by filtration through a Milli-Q Academic A10 filtration unit prior to use.
    [Show full text]
  • Supplementary Information
    Electronic Supplementary Material (ESI) for Green Chemistry. This journal is © The Royal Society of Chemistry 2019 Supplementary Information Highly regioselective and sustainable solar click reaction: A new Post-synthetic modified triazole organic polymer as recyclable photocatalyst for regioselective azide-alkyne cycloaddition reaction Dolly Yadav,a Nem Singh,a Tae Wu Kim,b Jae Young Kim,a No-Joong Parka and Jin-Ook Baeg*a aArtificial Photosynthesis Research Group, Korea Research Institute of Chemical Technology (KRICT), 100 Jang-dong, Yuseong, Daejeon 34114, Republic of Korea E-mail:[email protected] bCenter for Nanomaterials and Chemical Reactions, Institute for Basic Science (IBS), Daejeon 34141, Korea. S. N. Contents Page no. 1. Experimental section S2-S3 2. Safety issues for handling azide compounds S3 3. Synthetic procedure S4-S18 4. Tables S1-S3 S19-S21 5. Figures S1-S12 S20-S28 6. Crystallographic data of 3bd- figure S12, table S4-S5 S29-S31 7. 1H, 13C and 19F NMR figure S13- S28 S32-S86 8. References S86 S1 Experimental Section 1.1 Materials All the reagents utilized in synthesis were purchased from commercial suppliers, unless or otherwise stated. Sodium Azide, disodium 4,4’-diaminostilbene disulfonate, sodium nitrite, 1,8- diazabicyclo[5,4,0]undec-7-ene, propargyl alcohol, propargyl bromide (80% in toluene), perylene tetracarboxylic anhydride were purchased from Sigma Aldrich Korea. 2,6-difluorobenzylbromide, 2,4-difluorobenzylbromide, 3,5-Dimethylbenzylbromide, 4-bromobenzylbromide, 4- fluorobenzylbromide propiolic acid and methyl propiolate were also purchased from Sigma Aldrich. The solvents DMF, DCM, acetone, ethyl acetate were purchase from Junsei Chemicals Company. Caution sodium azide is considered to be explosive, hence necessary precautions fume hood, safety glasses etc should be taken while carrying out the reaction.
    [Show full text]
  • The Synthetic-Technical Development of Oseltamivir Phosphate Tamiflu<Sup>
    HOT TOPICS: SANDMEIER PRIZE 2006 93 doi:10.2533/chimia.2007.93 CHIMIA 2007, 61, No. 3 Chimia 61 (2007) 93–99 © Schweizerische Chemische Gesellschaft ISSN 0009–4293 The Synthetic-Technical Development of Oseltamivir Phosphate TamifluTM: A Race against Time Stefan Abrechta , Muriel Cordon Federspielb , Heinrich Estermannb , Rolf Fischerb , Martin Karpf*a , Hans-Jürgen Mairb , Thomas Oberhauserc , Gösta Rimmlerb , René Trussardia , and Ulrich Zuttera Recipients of the Sandmeyer Prize 2006 of the Swiss Chemical Society Abstract: The clinical development of the first orally available neuraminidase inhibitor prodrug oseltamivir phos- phate (TamifluTM) proceeded very fast. In order to support this program an unprecedented team effort in chemical process research, development, piloting, production and analytics took place, which allowed the successful launch of TamifluTM in 1999, only two and a half years after it was licensed from Gilead Sciences. This article describes selected aspects of the commercially used synthesis route and a brief summary of alternative syntheses devised by Roche chemists. Keywords: Analytics · Influenza neuraminidase inhibitor · Oseltamivir phosphate · Production · Synthesis · Technical development 1. Introduction H O H O CO H In September 1996 a license agreement be- H O 2 O CO Et tween Gilead Sciences, Foster City, Califor- 2 H O nia and F. Hoffmann-La Roche Ltd, Basel AcHN H N NH was signed for the co-development of the AcHN 2 NH2 •H3 PO4 novel orally available neuraminidase inhibi- NH tor prodrug molecule 1 (Fig. 1) patented by Gilead Sciences in February 1995,[1] today 1 2 known as oseltamivir phosphate, trade name TamifluTM. In April 1999, after only two and Oseltamivir phosphate Zanamivir a half years of development time, a new drug TamifluTM RelenzaTM GS-4104-02 GG-167 application (NDA) for 1 was filed with the RO0640796-002 US Food and Drug Administration (FDA) for the use of 1 for the treatment of influenza Fig.
    [Show full text]
  • Chem 314 Preorganic Evaluation
    Organic Reaction Guide Beauchamp 1 Chem 316 / Beauchamp Reactions Review Sheet Name SN2 Reactions - special features: biomolecular kinetics Rate = kSN2[RX][Nu ], single step concerted reaction, E2 is a competing reaction o o o o relative order of reactivity: CH3X > 1 RX > 2 RX >> 3 RX (based on steric hinderance, no SN2 at 3 RX) allylic & benzylic RX are very reactive, adjacent pi bonds help stabilize transition state and lower TS energy (Ea) o complete substitution at Cα (3 RX) or Cβ (neopentyl pattern) almost completely inhibits SN2 reactions vinyl & phenyl are very unreactive, bonds are stronger and poor backside approach leaving group ability: OTs = I > Br > Cl in neutral or basic conditions (just like E2, SN1 adn E1), and neutral molecule leaving groups are good from protonated, cationic intermediates in acid conditions, + + + + -OH2 , -ORH , -OR2 , -NR3 , etc. we will consider all anions, ammonia, amines, thiols and sulfides to be strong nucleophiles (favors SN2 and E2 reactions) in our course some electron pair donors are mainly nucleophiles (sulfur, azide, cyanide, carboxylates) and - + + - + - some are mainly bases (t-BuO K , Na H2N , Na H ) polar, aprotic solvents work best for SN2 reactions because nucleophiles are relatively unencombered for electron doantion (dimethyl sulofoxide = DMSO, dimethylformamide = DMF, acetonitrile = AN, acetone, etc.) in our course some electron pair donors are mainly nucleophiles (sulfur, azide, cyanide, carboxylates) and we will consider neutral solvent molecules such as water, alcohols and acids to be weak nucleophiles (favors SN1 and E1) stereoselectivity: 100% inversion of configuration from backside atack regioselectivity: reacts at carbon with leaving group, completely unambiguous chemoselectivity: N/A The following list is designed to emphasize SN2 reactions.
    [Show full text]
  • Asymmetric Nitrene Transfer Reactions with Azides Via Co(II)-Based Metalloradical Catalysis (MRC) Jingran Tao University of South Florida, [email protected]
    University of South Florida Scholar Commons Graduate Theses and Dissertations Graduate School January 2013 Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC) Jingran Tao University of South Florida, [email protected] Follow this and additional works at: http://scholarcommons.usf.edu/etd Part of the Chemistry Commons Scholar Commons Citation Tao, Jingran, "Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC)" (2013). Graduate Theses and Dissertations. http://scholarcommons.usf.edu/etd/4590 This Dissertation is brought to you for free and open access by the Graduate School at Scholar Commons. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Scholar Commons. For more information, please contact [email protected]. Asymmetric Nitrene Transfer Reactions with Azides via Co(II)-Based Metalloradical Catalysis (MRC) by Jingran Tao A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy Department of Chemistry College of Arts and Sciences University of South Florida Major Professor: X. Peter Zhang, Ph.D. Jon Antilla, Ph.D. Wayne Guida, Ph.D. Xiao Li, Ph.D. Date of Approval: April 3rd , 2013 Keywords: cobalt, porphyrin, catalysis, aziridination, C–H amination, azide, asymmetric Copyright © 2013, Jingran Tao Dedication I dedicate this dissertation to my beloved parents. Acknowledgments I need to begin with thanking Dr. Peter Zhang for his continuous guidance and support. I learned the words “determination” and “believe” from him. I also need to thank my committee members: Dr. Jon Antilla, Dr. Wayne Guida Dr. Xiao Li and Chair Dr.
    [Show full text]