DOCSLIB.ORG

1-Cyclohexane Acetic Acid

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
1-Cyclohexane Acetic Acid (19) & (11) EP 2 275 401 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 19.01.2011 Bulletin 2011/03 C07C 205/00 (2006.01) C07C 261/00 (2006.01) C07C 269/00 (2006.01) C07C 271/00 (2006.01) (21) Application number: 10013362.8 (22) Date of filing: 11.06.2003 (84) Designated Contracting States: • Manthati, Suresh Kumar CH IE LI Cupertino, CA 95014 (US) • Xiang, Jia-Ning (30) Priority: 11.06.2002 US 171485 Palo Alto, CA 94303 (US) • Gallop, Mark A. (62) Document number(s) of the earlier application(s) in Los Altos, CA 94022 (US) accordance with Art. 76 EPC: 03757492.8 / 1 554 237 (74) Representative: Wytenburg, Wilhelmus Johannes et al (71) Applicant: XenoPort, Inc. Mewburn Ellis LLP Santa Clara, CA 95051 (US) 33 Gutter Lane London (72) Inventors: EC2V 8AS (GB) • Raillard, Stephen P. Mountain View, CA 94040 (US) Remarks: • Zhou, Cindy X. This application was filed on 06-10-2010 as a Palo Alto, CA 94303 (US) divisional application to the application mentioned • Yao, Fenmei under INID code 62. Mountain View, CA 94040 (US) (54) Crystalline 1-{[(a-isobutanoyloxyethoxy)carbonyl]aminomethyl}-1-cyclohexane acetic acid (57) The present invention relates to crystalline 1-{[( α-isobutanoyloxyethoxy)carbonyl] aminomethyl}-1-cyclohexane acetic acid. EP 2 275 401 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 275 401 A1 Description Field 5 [0001] Methods for synthesis of 1-(acyloxy)-alkyl carbamates are provided. More particularly, the synthesis of prodrugs (i.e., 1-(acyloxy)-alkyl carbamates of GABA analogs) from 1- haloalkyl carbamates of GABA analogs are described. Also described are new 1-haloalkyl carbamates of GABA analogs. Background 10 [0002] One solution to drug delivery and/or bioavailability issues in pharmaceutical development is converting known drugs to prodrugs. Typically, in a prodrug, a polar functional group (e.g., a carboxylic acid, an amino group, a hydroxyl group, etc.) is masked by a promoiety, which is labile under physiological conditions. Accordingly, prodrugs are usually transported through hydrophobic biological barriers such as membranes and typically possess superior physicochemical 15 properties than the parent drug. [0003] Pharmacologically effective prodrugs are non-toxic and are preferably selectively cleaved at the locus of drug action. Ideally, cleavage of the promoiety occurs rapidly and quantitatively with the formation of non-toxic by-products (i.e., the hydrolyzed promoiety). [0004] The acyloxyalkoxycarbonyl functionality is an example of a promoiety that may be used to modulate the phys- 20 iochemical properties of pharmaceuticals (Alexander, United States Patent No. 4,916,230; Alexander, United States Patent No. 5,733,907; Alexander et al., U.S. Patent No. 4,426,391). Typically, 1-(acyloxy)-alkyl derivatives of a phar- maceutical possess superior bioavailability, may be less irritating to topical and gastric mucosal membranes and are usually more permeable through such membranes when compared to the parent drug. [0005] However, although 1-(acyloxy)-alkyl ester derivatives of alcohols and 1-(acyloxy)-alkyl carbamate derivatives 25 of amines have been frequently used to mask these polar functional groups in pharmaceuticals, existing synthetic methods for preparing these desirable derivatives are inadequate. Methods disclosed in the art for synthesis of acyloxy- alkyl esters and carbamates are typically multi-step routes that utilize unstable intermediates and/or toxic compounds or salts and accordingly are difficult to perform on large scale (Alexander, United States Patent No. 4,760,057; Lund, United States Patent No. 5,401,868; Alexander, United States Patent No. 4,760,057; Saariet al., European Patent 30 0416689B1). [0006] Accordingly, there is a need for a new synthesis of 1-(acyloxy)-alkyl derivatives that proceeds rapidly and efficiently, which is amenable to scale-up and proceeds through readily accessible synthetic precursors. Summary 35 [0007] A method for synthesizing 1-(acyloxy)-alkyl derivatives from acyloxy derivatives, which typically proceeds in high yield, does not necessarily require the use of heavy metals and is readily amenable to scale- up is provided herein. [0008] In a first aspect, a method of synthesizing a compound of Formula (I) is provided which comprises 40 45 50 55 2 EP 2 275 401 A1 5 contacting a compound of Formula (II), a compound of Formula ( III) and at least one equivalent of a metal salt wherein: 10 X is F, Cl, Br or I; n is 0 or 1; R1 is acyl, substituted acyl, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, 15 substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; R2 and R3 are independently hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl, or optionally, R2 and R3 together with the atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, 20 cycloheteroalkyl or substituted cycloheteroalkyl ring; R4 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; R5 is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, alkoxycarbonyl, substituted 25 alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl, or optionally, R 4 and R 5 together with the atoms to which they are attached form a cycloheteroalkyl or substituted cycloheteroalkyl ring; R6 and R 9 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted 30 aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl and substituted heteroarylalkyl; R7 and R 8 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, acyl, substituted acyl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroarylalkyl and substituted heteroarylalkyl, or optionally, R 7 and R 8 together with the carbon atom to which they 35 are attached form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl or bridged cy- cloalkyl ring; and R10 is hydrogen, alkyl,substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, aryldialkylsilyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl or trialkylsilyl. 40 [0009] In a second aspect a method of synthesizing a compound of Formula (I) is provided which comprises 45 50 55 3 EP 2 275 401 A1 5 10 15 contacting a compound of Formula (II), a compound of Formula (III) and at least one equivalent of an organic base, 20 where X, n, R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10 are as defined, supra. [0010] In a third aspect a compound of Formula (II) is provided, 25 30 wherein: 35 X is F, Cl, Br or I; n is 0 or 1; R2 and R3 are independently hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl, 40 or optionally, R2 and R3 together with the atom to which they are bonded form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring; R4 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl; heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl; 45 R5 is hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, acyl, substituted acyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbamoyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl, or optionally, R 4 and R 5 together with the atoms to which they are attached form a cycloheteroalkyl or substituted cycloheteroalkyl ring; 50 R6 and R 9 are independently selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl and substituted
Load more

Recommended publications
  • 14 Title: Coal Review of Hydrocarbon Emissions Related to Tar Pitch
    AP42 Section 7.1 Related: 14 Title: Review of Hydrocarbon Emissions Related to Coal Tar Pitch. Includes pitch vapor pressure data and Antoine's coefficients. EF Bart, et al. Allied Chemical Corporation 1980 I ._ ,.. ?i e!,/..'. r'.:.. ,,T.<,ili -:*., $0 ,i .# 1 .... i;.'.,.,: _..:, '">,U<>j. .. .. REVIEW OF HYDROCMSON EMISSIONS RELATED TO COAL TAR PITCH E. F. Bart, S. A. Visnic, P. A. Cerria Allied Chemical Corporation Morristown, New Jersey 07960 Sumnary Coal tar pitch is used primarily as a binder in the manufacture of carbon electrodes for the aluminum and steel industries. The pitch repre- sents the main product from the continuous, high-temperature distillation of coke oven tar. The pitch is produced and generally handled as a liquid at high temperatures, thus resulting in a potential for hydrocarbon emissions during its handling. An ever-increasing need for control of hydrocarbon emissions has resulted for process and storage equipment since amendments were made in 1977 to the Clean Air Act. Within the next several years, most industries will be faced with requirements for the installation of air pollution con- trol equipment. This paper deals with the types of emissions and methods used in quantifying and controlling emissions from coal tar pitch storage equipment. To better understand the nature of coal tar pitch, a brief description is given of its origin, chemistry and physical properties. Coal Tar Distillation Coal tar pitch is the residue from the distillation of coal tar and represents from 30% to 60% of the tar. It is a complex, bituminous sub- stance and has been estimated to contain about 5,000 compounds.
    [Show full text]
  • Polycyclic Aromatic Hydrocarbon Structure Index
    NIST Special Publication 922 Polycyclic Aromatic Hydrocarbon Structure Index Lane C. Sander and Stephen A. Wise Chemical Science and Technology Laboratory National Institute of Standards and Technology Gaithersburg, MD 20899-0001 December 1997 revised August 2020 U.S. Department of Commerce William M. Daley, Secretary Technology Administration Gary R. Bachula, Acting Under Secretary for Technology National Institute of Standards and Technology Raymond G. Kammer, Director Polycyclic Aromatic Hydrocarbon Structure Index Lane C. Sander and Stephen A. Wise Chemical Science and Technology Laboratory National Institute of Standards and Technology Gaithersburg, MD 20899 This tabulation is presented as an aid in the identification of the chemical structures of polycyclic aromatic hydrocarbons (PAHs). The Structure Index consists of two parts: (1) a cross index of named PAHs listed in alphabetical order, and (2) chemical structures including ring numbering, name(s), Chemical Abstract Service (CAS) Registry numbers, chemical formulas, molecular weights, and length-to-breadth ratios (L/B) and shape descriptors of PAHs listed in order of increasing molecular weight. Where possible, synonyms (including those employing alternate and/or obsolete naming conventions) have been included. Synonyms used in the Structure Index were compiled from a variety of sources including “Polynuclear Aromatic Hydrocarbons Nomenclature Guide,” by Loening, et al. [1], “Analytical Chemistry of Polycyclic Aromatic Compounds,” by Lee et al. [2], “Calculated Molecular Properties of Polycyclic Aromatic Hydrocarbons,” by Hites and Simonsick [3], “Handbook of Polycyclic Hydrocarbons,” by J. R. Dias [4], “The Ring Index,” by Patterson and Capell [5], “CAS 12th Collective Index,” [6] and “Aldrich Structure Index” [7]. In this publication the IUPAC preferred name is shown in large or bold type.
    [Show full text]
  • The Study of the Absoiption Spectra of the Hydrocarbons Isolated from the Products of the Action of Alunzinium Chloride on Nup12tkccle.R~E
    View Article Online / Journal Homepage / Table of Contents for this issue ABSORPTION SPECTRA OF HYDROCARBONS. 1319 Published on 01 January 1908. Downloaded by University of California - San Diego 12/04/2016 06:21:24. CXXV1.-The Study of the Absoiption Spectra of the Hydrocarbons isolated from the Products of the Action of Alunzinium Chloride on Nup12tkccle.r~e. By ANNIEHOMER, Fellow of Newnham College, and JOHNEDWARD PURVIS, M.A. FROMthe products of the action of aluminium chloride on naphthalene, besides PP-dinaphthyl previously isolated by Friedel and Crafts from the same reaction, there have been isolated three new hydrocarbons which have been described in detail by one of us (Homer, Trans., 1907, 9 1, 1103). The substances isolated were : (.i) CI4Hl6, a homologue of naphthalene, either tetramethyl- or 4s2 View Article Online 1320 HOMER AND PURVIS: THE STUDY OF THE diethyl-naphthalene, more probably the former ; (ii) CZ0Hl4, /3@-dinaphthyl; (iii) c26H22, a substance supposed to be a homologue of dinaphthanthracene, C,,H14 ; and (iv) C40H26, probably tetra- naph t h yl. @B-Dinaphthylis formed by the condensation of two naphthalene molecules. It was thought that the hydrocarbon C,,HZ6 was formed by the condensation of either two PP-dinaphthgl or four naphthalene molecules, more probably by the former, as an increase in the time allowed for the action of aluminium chloride on naphthalene, or a rise in the temperature at which the reaction was conducted, caused a decrease in the amount of the hydrocarbon aad an increase in the amount of the hydrocarbon C,,H,, produced. It was suggested that the substance C261322was a homologue of dinaphthanthracene, CZ2Hl4,and its formation from alkylnaphthalenes, which are also formed during the reaction, was given as follows : The intense fluorescence of the substance suggested the presence of an anthracenoid linking, In the method of formation thus proposed, hydrogen would be eliminated from a /3-methyl group of trimethylnaphthalene.
    [Show full text]
  • Absence of Photoemission from the Fermi Level in Potassium Intercalated Picene and Coronene films: Structure, Polaron Or Correlation Physics?
    Absence of photoemission from the Fermi level in potassium intercalated picene and coronene films: structure, polaron or correlation physics? Benjamin Mahns,1 Friedrich Roth,1 and Martin Knupfer1 IFW Dresden, P.O. Box 270116, D-01171 Dresden, Germany (Dated: 13 September 2018) The electronic structure of potassium intercalated picene and coronene films has been studied using photoemission spectroscopy. Picene has additionally been intercalated using sodium. Upon alkali metal addition core level as well as valence band pho- toemission data signal a filling of previously unoccupied states of the two molecular materials due to charge transfer from potassium. In contrast to the observation of superconductivity in Kxpicene and Kxcoronene (x ∼ 3), none of the films studied shows emission from the Fermi level, i. e. we find no indication for a metallic ground state. Several reasons for this observation are discussed. arXiv:1203.4728v1 [cond-mat.supr-con] 21 Mar 2012 1 I. INTRODUCTION Superconductivity always has attracted a large number of researchers since this phe- nomenon harbors challenges and prospects both under fundamental and applied points of view. Very recently, it has been discovered that some molecular crystal consisting of poly- cyclic aromatic hydrocarbons demonstrate superconductivity upon alkali metal addition. Furthermore, these compounds are characterized by rather high transition temperatures into 1 2 the superconducting state, for instance K3picene (Tc=18 K) and K3coronene (Tc=15 K) . Most recently, superconductivity with a transition temperature of 33 K has been reported 3 for K3dibenzopentacene . These doped aromatic hydrocarbons thus represent a class of or- ganic superconductors with transition temperatures only slightly below that of the famous 4{8 alkali metal doped fullerenes with Tc's up to 40 K .
    [Show full text]
  • Prcn.Uppderlimit Of
    564 MARCH 29, THE CANCER-PRODUCING FACTOR IN TAR. rTRBTETISU 19241 IMDICAIJOURNAr. I wlhiel eacll fraction is produced; the figures are onlv very ON THE CANCER-PRODUCING FACTOR rouglh, for the practice varies considerably in different tar- IN TAR. works, and also in the same works in accordance with fluctuiations in the BY miiarket for different products. Tlhus the proportion of creosote oil produced may vary from 9 per E. L. KENNAWAY, M.D., D.Sc. cent. to 25 per cent. of the crude tar. (From the Cancer Hospital Research Institute, London.) TABLE I.-Fi'ractions of Gasworks Tar. TH.AT tar can produce cancer has been known for nearly fifty years, but no systematic attemipt to tlle par- Limit of idenitify Fraction. PrCn.UppDer ticular comiipounds responsible for this effect was possible Pof TCar. Temperature until tlleexperimental productionof cancer in lower animals a became practical method. In thle absence of such experi- 1. Ammoniacal liquor ... ... 2 nmenltal evidence from the laboratory, th'e capacity of any 2. Crude naphtha ... ... ... 2 material to produce cancer must be learned from those accidental experiments on man which are the cause of 3. Light oil ... ... ... ... 9 2250 "industrial diseases." When a new cancer-producing 4. Middle or carbolic oil ... ... 5 2550 substance comes into industrial use on a large scale no danger will be detected during the long latent period, 5. Creosote oil ... ... ... ... 14 2750 whieh in man is probably of many years' duration; the 6. Anthracene oil ... ... 3 320P* effect of the will then become apparent, as we substaneo 7. Pitch ... ... ... ... ... ...63 have seen recently in the case of mule-spinners.
    [Show full text]
  • Certificate of Analysis
    National Institute of Standards & Technology Certificate of Analysis Standard Reference Material® 1597a Complex Mixture of Polycyclic Aromatic Hydrocarbons from Coal Tar This Standard Reference Material (SRM) is intended for use in the evaluation and validation of analytical methods for the determination of a natural, combustion-related mixture of polycyclic aromatic hydrocarbons (PAHs). SRM 1597a is isolated from a coal tar sample and dissolved in toluene. It is suitable for direct analysis (i.e., without sample cleanup or concentration) in the determination of PAHs using analytical techniques such as gas chromatography (GC), liquid chromatography (LC), or gas chromatography/mass spectrometry (GC/MS). This SRM may also be used to evaluate procedures for measurement of mutagenic activity of combustion-related mixtures of PAHs and related compounds. A unit of SRM 1597a consists of one 5 mL ampoule, containing 1.3 mL of material. Certified Mass Fraction Values: Certified values for concentrations, expressed as mass fractions, for 34 PAHs are provided in Table 1. The certified values are based on the agreement of results obtained at NIST from two or more chemically independent analytical techniques [1,2]. A NIST certified value is a value for which NIST has the highest confidence in its accuracy in that all known or suspected sources of bias have been investigated or accounted for by NIST. Reference Mass Fraction Values: Reference values for concentrations, expressed as mass fractions, are provided for 36 additional PAHs in Table 2 and for 10 polycyclic aromatic sulfur heterocycles (PASH) in Table 3. Reference values are given in Table 4 for the mutagenic activity of SRM 1597a.
    [Show full text]
  • DP70323.Pdf (5.434Mb)
    PART I THE SELEHXUM DKHYDKOOKNATIOH OF URSOLIC ACIB PART II THE PREPARATION OF MBTBOXY AC 8 TAL&EBYCB BY BARRY II * DUVALL01 Cl n€ m LD o7 ? 3 , Ml od X V v a U , H - M r+i; &- Thesis submitted to the Faculty of the Graduate School of the University of Merylend In partial fulfillment of the requirements for the degree of Doctor of Philosophy* CHEMISTRY LIBRARY 1956 * jjniverslty o p m a r y l a h d UMI Number: DP70323 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 complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. UMI Dissertation Publishing UMI DP70323 Published by ProQuest LLC (2015). Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ACKNOWLEDGMENT The writer wished to express his appreciation to Dr* N* L. Drake for suggesting these problems and for his constant advice and attention during the course of this research. TABLE OF C0HTE8TS FART I The Selenium Dehydrogenation of Orsolie Acid Page 1* Historical Introduction 1 A. Ursolic Acid ....... ............ 1 B« Selenium Dehydrogenation .......... 25 2* Experimental Part ......... ...... 41 A* Purification of Ursolic Acid ........... 41 B. Dehydrogenation Experiments ...... 44 5* Discussion of Results .....................
    [Show full text]
  • United States Patent Office. Harry F
    ul Patented July 6, 1926. 1,591,712 UNITED STATES PATENT OFFICE. HARRY F. T.EWIS, OE BUFFALO, NEW YORK, ASSIGNOR, to NATIONAL ANILINE & CHEMICAL COMPANY, INC., OF NEW YORK, N. Y., A. CORPORATION OF NEW YORK. PURIFICATION OF ANTHRAQUINONE. No Drawing. Application filed IIarch 4, 1920. Serial No. 363,261. This invention relates to the purification lar alkali employed. The strength of the of anthraquinone, and more particularly to alkali solution can also be varied, from rela the purification of anthraquinone admixed tively dilute solutions to concentrated solu With other oxidation products, such as the tions. The purification is best effected at oxidation products of carbazol and other a temperature between about 50 and 100° C., nitrogen bases and the carboxy and phenolic but lower temperatures may be used. The 60 Oxidation products of other hydrocarbons. inpurities particularly removed by such In the production of anthraquinone by alkaline treatment are those above indicated, Oxidizing anthracene, for example, with a namely, the oxidation products of carbazol O Solution of chromic acid, or with an acid and other nitrogen bases, as well as the Solution of sodium or potassium dichro carboxy and phenolic oxidation products of mate, such impurities as are admixed with Such hydrocarbons as methylanthracene. the anthracene are subjected to the same phenanthrene, acenaphthene, etc., and oxida Oxidizing agent or agents as is the anthra tion products which contain chromium as a s cene itself. As a result, the anthraquinone constituent. produced, after separating the constituents In the preferred practice of the inven O which are soluble in Water or in the acid tion, the crude anthraquinone is extracted Solution, contains various impurities in ad with hot alkaline solution in amount, from mixture therewith.
    [Show full text]
  • Toxicological Profile for Wood Creosote, Coal Tar Creosote, Coal Tar, Coal Tar Pitch, and Coal Tar Pitch Volatiles
    TOXICOLOGICAL PROFILE FOR WOOD CREOSOTE, COAL TAR CREOSOTE, COAL TAR, COAL TAR PITCH, AND COAL TAR PITCH VOLATILES U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 2002 CREOSOTE ii DISCLAIMER The use of company or product name(s) is for identification only and does not imply endorsement by the Agency for Toxic Substances and Disease Registry. CREOSOTE iii UPDATE STATEMENT Toxicological profiles are revised and republished as necessary, but no less than once every three years. For information regarding the update status of previously released profiles, contact ATSDR at: Agency for Toxic Substances and Disease Registry Division of Toxicology/Toxicology Information Branch 1600 Clifton Road NE, E-29 Atlanta, Georgia 30333 V FOREWORD This toxicological profile is prepared in accordance with guidelines" developed by the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA). The original guidelines were published in the Federal Register on April 17, 1987. Each profile will be revised and republished as necessary. The ATSDR toxicological profile succinctly characterizes the toxicologic and adverse health effects information for the hazardous substance described therein. Each peer-reviewed profile identifies and reviews the key literature that describes a hazardous substance's toxicologic properties. Other pertinent literature is also presented, but is described in less detail than the key studies. The profile is not intended to be an exhaustive document; however, more comprehensive sources of specialty information are referenced. The focus of the profiles is on health and toxicologic information; therefore, each toxicological profile begins with a public health statement that describes, in nontechnical language, a substance's relevant toxicological properties.
    [Show full text]
  • Environmental Health Criteria 171
    Environmental Health Criteria 171 DIESEL FUEL AND EXHAUST EMISSIONS Please note that the layout and pagination of this web version are not identical with the printed version. Diesel fuel and exhaust emissions (EHC 171, 1996) UNITED NATIONS ENVIRONMENT PROGRAMME INTERNATIONAL LABOUR ORGANISATION WORLD HEALTH ORGANIZATION INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY ENVIRONMENTAL HEALTH CRITERIA 171 DIESEL FUEL AND EXHAUST EMISSIONS This report contains the collective views of an international group of experts and does not necessarily represent the decisions or the stated policy of the United Nations Environment Programme, the International Labour Organisation, or the World Health Organization. Environmental Health Criteria 171 DIESEL FUEL AND EXHAUST EMISSIONS First draft prepared by the staff members of the Fraunhofer Institute of Toxicology and Aerosol Research, Germany, under the coordination of Dr. G. Rosner Published under the joint sponsorship of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization, and produced within the framework if the Inter-Organization Programme for the Sound Management of Chemicals. World Health Organization Geneva, 1996 The International Programme on Chemical Safety (IPCS) is a joint venture of the United Nations Environment Programme, the International Labour Organisation, and the World Health Organization. The main objective of the IPCS is to carry out and disseminate evaluations of the effects of chemicals on human health and the quality of the environment. Supporting activities include the development of epidemiological, experimental laboratory, and risk-assessment methods that could produce internationally comparable results, and the Page 1 of 287 Diesel fuel and exhaust emissions (EHC 171, 1996) development of manpower in the field of toxicology.
    [Show full text]
  • Part I the Selenium Dehydrogenation Op
    PART I THE SELENIUM DEHYDROGENATION OP PRIEDELINOL PART II THE BROMINATION OP FRIEDELIN BY . \ WILLARD TV HASKINS \ \ Thesis submitted to the Faculty of the Graduate School of the University of Maryland In partial fulfillment of the requirements for the degree of Doctor of Philosophy* 1936 • UMI Number: DP70114 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 complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. Dissertation Publishing UMI DP70114 Published by ProQuest LLC (2015). Copyright in the Dissertation held by the Author. Microform Edition © ProQuest LLC. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code uest ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 ACKNOWLEDGMENT The writer Is Indebted to Dr* N* L# Drake, under whose direction and advice this work was carried out* TABLE OF CONTENTS Page PART I Review or Literature ...••.•» 1 Introduction ... 11 Experimental ...... 15 Conclusions ....... ... 28 Summary ............................... 29 Bibliography ..................... 50 PART XI Introduction * • •.... 51 Experimental...... 55 Conclusions •. * 55 REVIEW OP LITERATURE ON TRITERPENES PROM 1933 TO DATE* Ruzicka, previous to 1933, had proposed a structural formula (I) for the carbon skeleton of the trlterpenes based
    [Show full text]
  • Nationwide Increase of Polycyclic Aromatic Hydrocarbons in Ultrafine
    Atmos. Chem. Phys., 20, 14581–14595, 2020 https://doi.org/10.5194/acp-20-14581-2020 © Author(s) 2020. This work is distributed under the Creative Commons Attribution 4.0 License. Nationwide increase of polycyclic aromatic hydrocarbons in ultrafine particles during winter over China revealed by size-segregated measurements Qingqing Yu1, Xiang Ding1,4, Quanfu He1, Weiqiang Yang5, Ming Zhu1,2, Sheng Li1,2, Runqi Zhang1,2, Ruqin Shen1, Yanli Zhang1,3,4, Xinhui Bi1,4, Yuesi Wang3,6, Ping’an Peng1,4, and Xinming Wang1,2,3,4 1State Key Laboratory of Organic Geochemistry and Guangdong Key Laboratory of Environmental Protection and Resources Utilization, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou 510640, China 2University of Chinese Academy of Sciences, Beijing 100049, China 3Center for Excellence in Regional Atmospheric Environment, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen 361021, China 4Guangdong-Hong Kong-Macao Joint Laboratory for Environmental Pollution and Control, Guangzhou Institute of Geochemistry, Chinese Academy of Science, Guangzhou 510640, China 5Guangdong Provincial Academy of Environmental Science, Guangzhou 510045, China 6State Key Laboratory of Atmospheric Boundary Layer Physics and Atmospheric Chemistry, Institute of Atmospheric Physics, Chinese Academy of Sciences, Beijing 100029, China Correspondence: Xinming Wang ([email protected]), and Xiang Ding ([email protected]) Received: 10 June 2020 – Discussion started: 22 June 2020 Revised: 13 October 2020 – Accepted: 14 October 2020 – Published: 1 December 2020 3 Abstract. Polycyclic aromatic hydrocarbons (PAHs) are BaPeq (8.48 vs. 1.34 ng/m / and PAHs’ inhalation cancer risk toxic compounds in the atmosphere and have adverse effects (7.4 × 10−4 vs.
    [Show full text]