DOCSLIB.ORG

Oral Preparation Comprising Specific Organic Acid, and Method for Improvement in Elution Property and Chemical Stability of Oral Preparation

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Oral Preparation Comprising Specific Organic Acid, and Method for Improvement in Elution Property and Chemical Stability of Oral Preparation (19) & (11) EP 2 168 579 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 153(4) EPC (43) Date of publication: (51) Int Cl.: 31.03.2010 Bulletin 2010/13 A61K 31/485 (2006.01) A61K 9/14 (2006.01) A61K 9/20 (2006.01) A61K 9/48 (2006.01) (2006.01) (2006.01) (21) Application number: 08752992.1 A61K 47/12 A61K 47/16 A61P 1/14 (2006.01) A61P 13/02 (2006.01) (2006.01) (2006.01) (22) Date of filing: 20.05.2008 A61P 17/04 A61P 25/04 C07D 489/02 (2006.01) (86) International application number: PCT/JP2008/059196 (87) International publication number: WO 2008/143240 (27.11.2008 Gazette 2008/48) (84) Designated Contracting States: • MINAKAMI, Satoshi AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Kamakura-shi HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT Kanagawa 248-8555 (JP) RO SE SI SK TR • TOKUMITSU, Hiroyuki Designated Extension States: Kamakura-shi AL BA MK RS Kanagawa 248-8555 (JP) (30) Priority: 21.05.2007 JP 2007133854 (74) Representative: Webster, Jeremy Mark et al Mewburn Ellis LLP (71) Applicant: Toray Industries, Inc. 33 Gutter Lane Tokyo 103-8666 (JP) GB-London EC2V 8AS (GB) (72) Inventors: • OHTA, Kotoe Kamakura-shi Kanagawa 248-8555 (JP) (54) ORAL PREPARATION COMPRISING SPECIFIC ORGANIC ACID, AND METHOD FOR IMPROVEMENT IN ELUTION PROPERTY AND CHEMICAL STABILITY OF ORAL PREPARATION (57) A chemically stable oral preparation with an ex- cellent dissolution property comprising as an effective ingredient a specific morphinan derivative or a pharma- ceutically acceptable acid addition salt thereof is dis- closed. The oral preparation according to the present in- vention comprises a specific morphinan derivative or a pharmaceutically acceptable acid addition salt thereof as an effective ingredient and an organic acid, wherein 1 g of said organic acid requires not less than 30 mL of water to dissolve in at 20°C. The method for improving disso- lution property and chemical stability of an oral prepara- tion according to the present invention comprises incor- porating an organic acid in the oral preparation compris- ing as an effective ingredient a specific morphinan deriv- ative or a pharmaceutically acceptable acid addition salt thereof, wherein 1 g of said organic acid requires not less than 30 mL of water to dissolve in at 20°C. EP 2 168 579 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 168 579 A1 Description Technical Field 5 [0001] The present invention relates to chemically stable oral preparations having high dissolution property, comprising a specific organic acid and as an effective ingredient a morphinan derivative having a nitrogen-containing heterocyclic group or a pharmaceutically acceptable acid addition salt thereof. Background Art 10 [0002] It is disclosed that specific morphinan derivatives having a nitrogen-containing cyclic group or pharmaceutically acceptable acid addition salts thereof, which have a remarkable therapeutic or prophylactic effect against pollakiuria or urinary incontinence, antipruritic effect, analgesic effect, and therapeutic or prophylactic effect against functional bowel disorder, are useful as a therapeutic agent for pollakiuria, antipruritic, analgesic and therapeutic or prophylactic agent 15 for functional bowel disorder (see, e.g., Patent Literatures 1, 2, 3 and 10). However, morphinan derivatives are known to be chemically unstable to light, heat or oxygen (see, e.g., Patent Literature 4), and actually it was confirmed that morphinan derivatives described in Patent Literatures 1 to 3 are also unstable. Therefore, it has been required to develop remedies with a good stability to ensure quality. In addition, the specific morphinan derivatives mentioned above are much slightly soluble in water, and have a problem in the dissolution property particularly in the neutral region. Thus, it 20 has been required to develop remedies with an improved dissolution property in the neutral region as well as a good chemical stability to ensure stable absorption. [0003] As a method for improving the dissolution property of various morphinan derivatives including morphine, a method in which the active ingredient is dissolved in oil or a solubilizer such as polyethylene glycol or surfactant (e.g., Patent Literature 5), and a method in which a remedy is prepared as a composition comprising a nonionic solubilizer, 25 lipophilic antioxidant and aqueous solvent (e.g., Patent Literature 6) have been reported. However, although Patent Literature 5 demonstrates that the active ingredients show a good dissolution property even after 6-month storage, it does not describe the data of chemical stability such as a change in the amount of decomposition products and the like. In Patent Literature 6, although it describes the effect of antioxidants on solubility and stability, the oral administration form is restricted to solutions or gels, and solid formulations such as tablets and capsules are not described. Moreover, 30 the two literatures do not disclose that the dissolution property can be improved by addition of a specific organic acid according to the present invention. [0004] As a method for improving the dissolution property of basic remedies, a method in which acidic compounds such as organic acids are added thereto, a method in which the dissolution rate is increased by pulverizing active substances with a grinder to increase the surface area, or the solid dispersion method in which the active substances 35 are dispersed in a polymer molecule such as polyethylene glycol or polyvinylpyrrolidone is generally used. However, it is known that pulverization not merely increases surface area of particles, but strongly affects on reactivity and stability of the solid, and the problem that destabilization occurs concurrently with improvement of the dissolution property has been pointed out. It has been also reported that, in the solid dispersion method, many amorphous particles of solid dispersions are often generated and that destabilization occurs due to the high surface energy of the amorphous particles 40 (e.g., Patent Literature 1). Thus, it is a very difficult problem to provide a chemically stable preparation with a high dissolution property containing a poorly soluble, unstable compound. [0005] On the other hand, as a method for stabilizing various morphinan derivatives including morphine, a method in which a basic component is added to morphine (e.g., Patent Literature 7), a method in which naloxone is combined with an antioxidant such as sodium thiosulfate or tocopherol (e.g., Patent Literature 8), and a method in which an antioxidant 45 such as sodium thiosulfate or propyl gallate is added to morphinan derivatives to stabilize the preparation (e.g., Patent Literature 4) have been disclosed. [0006] With respect to the effect of addition of organic acids on the chemical stability of morphinan derivatives, stabilized oral preparations comprising naloxone in combination with ascorbic acid and the like (e.g., Patent Literature 8), stabili- zation by adding an organic acid to naltrexone hydrochloride (e.g., Patent Literature 9), and stabilization by adding 50 ascorbic acid, erythorbic acid or citric acid to morphinan derivatives (e.g., Patent Literature 4) have been reported. However, none of these publications describes the solubility and the stabilizing effect of the organic acids to be added. In fact, it has been reported that stability is decreased when citric acid and tartaric acid are added to morphine (e.g., Patent Literature 7). [0007] Thus, these known techniques do not give the slightest suggestion of adding a specific organic acid to the 55 above-mentioned specific morphinan derivatives having a nitrogen-containing heterocyclic group or a pharmaceutically acceptable acid addition salt thereof in order to provide remedies with an excellent dissolution property and chemical stability. [0008] 2 EP 2 168 579 A1 Non-patent Literature 1: Mitsuru HASHIDA eds., "Designing and Evaluation of Oral Preparations", 1st Edition, Jihou Co., Ltd., February 10, 1995, p.167-179 Patent Literature 1: WO 2004/033457 Patent Literature 2: WO 2005/094826 5 Patent Literature 3: WO 2006/049248 Patent Literature 4: WO 99/02158 Patent Literature 5: JP 2960169 B Patent Literature 6: WO 2004/026231 Patent Literature 7: JP 2-160719 A 10 Patent Literature 8: WO 98/35679 Patent Literature 9: JP 2005-531515 A Patent Literature 10: WO 2007/055184 Disclosure of the Invention 15 Problems Which the Invention Tries to Solve [0009] An objection of the present invention is to provide a chemically stable oral preparation with an excellent disso- lution property comprising as an effective ingredient a specific morphinan derivative or a pharmaceutically acceptable 20 acid addition salt thereof. Means for Solving the Problem [0010] Since a preliminary experiment revealed that morphinan derivatives having a nitrogen-containing heterocyclic 25 group represented by the Formula (I) below are chemically unstable to light, heat and oxygen, the present inventors tried preparing various formulations selecting compatible additives and production methods based on the prior art infor- mation. However, it was proved that such common techniques are not effective enough to ensure stability and dissolution property. On the other hand, the dissolution property could be improved to some extent by adding an organic acid to the basic compound morphinan derivatives having a nitrogen- containing heterocyclic group represented by the Formula 30 (I). However, the effective ingredient was severely decomposed and destabilized depending on the type of
Load more

Recommended publications
  • Measuring and Predicting Sooting Tendencies of Oxygenates, Alkanes, Alkenes, Cycloalkanes, and Aromatics on a Unified Scale
    Measuring and Predicting Sooting Tendencies of Oxygenates, Alkanes, Alkenes, Cycloalkanes, and Aromatics on a Unified Scale Dhrubajyoti D. Dasa,1, Peter St. Johnb,1, Charles S. McEnallya,∗, Seonah Kimb, Lisa D. Pfefferlea aYale University, Department of Chemical and Environmental Engineering, New Haven CT 06520 bNational Renewable Energy Laboratory, Golden CO 80401 Abstract Soot from internal combustion engines negatively affects health and climate. Soot emissions might be reduced through the expanded usage of appropriate biomass-derived fuels. Databases of sooting indices, based on measuring some aspect of sooting behavior in a standardized combustion environment, are useful in providing information on the comparative sooting tendencies of different fuels or pure compounds. However, newer biofuels have varied chemical structures including both aromatic and oxygenated functional groups, making an accurate measurement or prediction of their sooting tendency difficult. In this work, we propose a unified sooting tendency database for pure compounds, including both regular and oxygenated hydrocarbons, which is based on combining two disparate databases of yield-based sooting tendency measurements in the literature. Unification of the different databases was made possible by leveraging the greater dynamic range of the color ratio pyrometry soot diagnostic. This unified database contains a substantial number of pure compounds (≥ 400 total) from multiple categories of hydrocarbons important in modern fuels and establishes the sooting tendencies of aromatic and oxygenated hydrocarbons on the same numeric scale for the first time. Using this unified sooting tendency database, we have developed a predictive model for sooting behavior applicable to a broad range of hydrocarbons and oxygenated hydrocarbons. The model decomposes each compound into single-carbon fragments and assigns a sooting tendency contribution to each fragment based on regression against the unified database.
    [Show full text]
  • Transport of Dangerous Goods
    ST/SG/AC.10/1/Rev.16 (Vol.I) Recommendations on the TRANSPORT OF DANGEROUS GOODS Model Regulations Volume I Sixteenth revised edition UNITED NATIONS New York and Geneva, 2009 NOTE The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the Secretariat of the United Nations concerning the legal status of any country, territory, city or area, or of its authorities, or concerning the delimitation of its frontiers or boundaries. ST/SG/AC.10/1/Rev.16 (Vol.I) Copyright © United Nations, 2009 All rights reserved. No part of this publication may, for sales purposes, be reproduced, stored in a retrieval system or transmitted in any form or by any means, electronic, electrostatic, magnetic tape, mechanical, photocopying or otherwise, without prior permission in writing from the United Nations. UNITED NATIONS Sales No. E.09.VIII.2 ISBN 978-92-1-139136-7 (complete set of two volumes) ISSN 1014-5753 Volumes I and II not to be sold separately FOREWORD The Recommendations on the Transport of Dangerous Goods are addressed to governments and to the international organizations concerned with safety in the transport of dangerous goods. The first version, prepared by the United Nations Economic and Social Council's Committee of Experts on the Transport of Dangerous Goods, was published in 1956 (ST/ECA/43-E/CN.2/170). In response to developments in technology and the changing needs of users, they have been regularly amended and updated at succeeding sessions of the Committee of Experts pursuant to Resolution 645 G (XXIII) of 26 April 1957 of the Economic and Social Council and subsequent resolutions.
    [Show full text]
  • Secondary Organic Aerosol Formation from the Ozonolysis of Cycloalkenes and Related Compounds*
    252 Chapter 7 Secondary Organic Aerosol Formation from the Ozonolysis of Cycloalkenes and Related Compounds* * This chapter is reproduced by permission from “Secondary organic aerosol formation from ozonolysis of cycloalkenes and related compounds” by M.D. Keywood, V. Varutbangkul, R. Bahreini, R.C. Flagan, J.H. Seinfeld, Environmental Science and Technology, 38 (15): 4157-4164, 2004. Copyright 2004, American Chemical Society. 253 7.1. Abstract The secondary organic aerosol (SOA) yields from the laboratory chamber ozonolysis of a series of cycloalkenes and related compounds are reported. The aim of this work is to investigate the effect of the structure of the hydrocarbon parent molecule on SOA formation for a homologous set of compounds. Aspects of the compound structures that are varied include the number of carbon atoms present in the cycloalkene ring (C5 to C8), the presence and location of methyl groups, and the presence of an exocyclic or endocyclic double bond. The specific compounds considered here are cyclopentene, cyclohexene, cycloheptene, cyclooctene, 1-methyl-1-cyclopentene, 1-methyl-1- cyclohexene, 1-methyl-1-cycloheptene, 3-methyl-1-cyclohexene, and methylene cyclohexane. SOA yield is found to be a function of the number of carbons present in the cycloalkene ring, with increasing number resulting in increased yield. Yield is enhanced by the presence of a methyl group located at a double-bonded site but reduced by the presence of a methyl group at a non-double bonded site. The presence of an exocyclic double bond also leads to a reduced yield relative to the equivalent methylated cycloalkene. On the basis of these observations, the SOA yield for terpinolene relative to the other cyclic alkenes is qualitatively predicted, and this prediction compares well to measurements of SOA yield from the ozonolysis of terpinolene.
    [Show full text]
  • Epoxidation of Cyclopentene, Cyclohexene and Cycloheptene by Acetylperoxyl Radicals
    Epoxidation of Cyclopentene, Cyclohexene and Cycloheptene by Acetylperoxyl Radicals J. R. Lindsay Smith, D. M. S. Smith, M. S. Stark* and D. J. Waddington Department of Chemistry, University of York, York, YO10 5DD, United Kingdom To further the current understanding of how peroxyl radicals add to C=C double bonds,eg. 1-3 a series of cyclic alkenes (cyclopentene, cyclohexene and cycloheptene) were reacted with acetylperoxyl radicals over the temperature range 373 - 433 K, via the co- oxidation of acetaldehyde, the cyclic alkene and a reference alkene. The resulting epoxides were monitored by GC-FID, allowing the determination of the Arrhenius parameters given in Table 1 for these addition reactions. 3 -1 -1 -1 Alkene log10(A / dm mol s ) Eact / kJ mol cyclopentene 9.7±0.6 31.2±5.0 cyclohexene 7.7±0.7 17.4±5.3 cycloheptene 8.8±0.8 25.5±6.5 cis-2-butene4 8.1±0.5 22.9±3.8 Table 1: Arrhenius parameters for the addition of acetylperoxyl radicals to cyclic alkenes and cis-2-butene. Parameters for cis-2-butene are also given for comparison,4 as it would be expected that a relatively unstrained cycloalkene would behave in a similar manner to this non-cyclic alkene; this is indeed found to be so, with no statistically significant difference between cyclohexene and cis-2-butene. Indeed the measured activation energy for cyclohexene fits in well with correlation between charge transfer ( Ec) and activation energy that is known to exist for the addition of acetylperoxyl to acyclic mono-alkenes.1 Cyclopentene however does have a significantly larger pre-exponential factor and activation energy than either cyclohexene or cis-2-butene.
    [Show full text]
  • Cycloalkanes, Cycloalkenes, and Cycloalkynes
    CYCLOALKANES, CYCLOALKENES, AND CYCLOALKYNES any important hydrocarbons, known as cycloalkanes, contain rings of carbon atoms linked together by single bonds. The simple cycloalkanes of formula (CH,), make up a particularly important homologous series in which the chemical properties change in a much more dramatic way with increasing n than do those of the acyclic hydrocarbons CH,(CH,),,-,H. The cyclo- alkanes with small rings (n = 3-6) are of special interest in exhibiting chemical properties intermediate between those of alkanes and alkenes. In this chapter we will show how this behavior can be explained in terms of angle strain and steric hindrance, concepts that have been introduced previously and will be used with increasing frequency as we proceed further. We also discuss the conformations of cycloalkanes, especially cyclo- hexane, in detail because of their importance to the chemistry of many kinds of naturally occurring organic compounds. Some attention also will be paid to polycyclic compounds, substances with more than one ring, and to cyclo- alkenes and cycloalkynes. 12-1 NOMENCLATURE AND PHYSICAL PROPERTIES OF CYCLOALKANES The IUPAC system for naming cycloalkanes and cycloalkenes was presented in some detail in Sections 3-2 and 3-3, and you may wish to review that ma- terial before proceeding further. Additional procedures are required for naming 446 12 Cycloalkanes, Cycloalkenes, and Cycloalkynes Table 12-1 Physical Properties of Alkanes and Cycloalkanes Density, Compounds Bp, "C Mp, "C diO,g ml-' propane cyclopropane butane cyclobutane pentane cyclopentane hexane cyclohexane heptane cycloheptane octane cyclooctane nonane cyclononane "At -40". bUnder pressure. polycyclic compounds, which have rings with common carbons, and these will be discussed later in this chapter.
    [Show full text]
  • Alkenes and Alkynes
    02/21/2019 CHAPTER FOUR Alkenes and Alkynes H N O I Cl C O C O Cl F3C C Cl C Cl Efavirenz Haloprogin (antiviral, AIDS therapeutic) (antifungal, antiseptic) Chapter 4 Table of Content * Unsaturated Hydrocarbons * Introduction and hybridization * Alkenes and Alkynes * Benzene and Phenyl groups * Structure of Alkenes, cis‐trans Isomerism * Nomenclature of Alkenes and Alkynes * Configuration cis/trans, and cis/trans Isomerism * Configuration E/Z * Physical Properties of Hydrocarbons * Acid‐Base Reactions of Hydrocarbons * pka and Hybridizations 1 02/21/2019 Unsaturated Hydrocarbons • Unsaturated Hydrocarbon: A hydrocarbon that contains one or more carbon‐carbon double or triple bonds or benzene‐like rings. – Alkene: contains a carbon‐carbon double bond and has the general formula CnH2n. – Alkyne: contains a carbon‐carbon triple bond and has the general formula CnH2n‐2. Introduction Alkenes ● Hydrocarbons containing C=C ● Old name: olefins • Steroids • Hormones • Biochemical regulators 2 02/21/2019 • Alkynes – Hydrocarbons containing C≡C – Common name: acetylenes Unsaturated Hydrocarbons • Arene: benzene and its derivatives (Ch 9) 3 02/21/2019 Benzene and Phenyl Groups • We do not study benzene and its derivatives until Chapter 9. – However, we show structural formulas of compounds containing a phenyl group before that time. – The phenyl group is not reactive under any of the conditions we describe in chapters 5‐8. Structure of Alkenes • The two carbon atoms of a double bond and the four atoms bonded to them lie in a plane, with bond angles of approximately 120°. 4 02/21/2019 Structure of Alkenes • Figure 4.1 According to the orbital overlap model, a double bond consists of one bond formed by overlap of sp2 hybrid orbitals and one bond formed by overlap of parallel 2p orbitals.
    [Show full text]
  • Spatial Variability of Air Pollutants in a Megacity Characterized by Mobile Measurements: Chemical Homogeneity Under Haze Conditions
    Supplementary Material for Spatial variability of air pollutants in a megacity characterized by mobile measurements: Chemical homogeneity under haze conditions Reza Bashiri Khuzestani1,a,★, Keren Liao1,★, Qi Chen1,*, Ying Liu1, Yan Zheng1, Xi Cheng1, Tianjiao Jia1, Xin Li1, Shiyi Chen1, Guancong Huang1 1State Key Joint Laboratory of Environmental Simulation and Pollution Control, BIC-ESAT and IJRC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China aNow at: Faculty of Civil, Water and Environmental Engineering, School of Engineering, Shahid Beheshti University, Tehran, Iran. ★These authors contributed equally to this work. *Correspondence to: Qi Chen ([email protected]) Table S1. The average concentrations of the 52 VOC species measured in this study compared with literature. These species are tentatively categorized into three groups including hydrocarbons (Group 1), aldehydes and ketones (Group 2), and acids and anhydrides (Group 3). Category Mean ± sd Mean ± sd * * Formula Assigned Name m/z KPTR Urban Suburb /Group (non-haze) (haze) + (CH3OH)H Methanol 33.033 2.22 n/a 16.82±14.81 44.69±15.96 11.77-51.76 3.4-5.6 + (C2H2O)H Ketenes 43.018 2.21 2 2.12±1.84 5.42±1.42 + (C2H4O)H Acetaldehyde 45.033 3.36 2 2.72±2.00 6.07±1.63 1.88-15.81 0.83-1.23 + (C2H6O)H Ethanol 47.049 2.18 n/a 25.35±32.19 98.28±32.17 + (C3H4O)H Acrolein; MTBE 57.033 3.35 2 0.30±0.27 0.60±0.14 (C H O)H+ Acetone + propanal 59.049 3 2 1.20±1.18 4.67±0.97 2.48-7.92 1.59-3.42 3 6 Isoprene; fragmentation of 2- methyl-3- + (C5H8)H buten-2-ol (MBO); fragmentation of 69.07 1.94 1 0.38±0.35 0.76±0.20 cyclohexanes species Methyl vinyl ketone + methacrolein; ted + (C4H6O)H 71.049 3.83 2 0.16±0.14 0.36±0.09 0.28-0.42 0.13-0.22 crotonaldehyde; ISOPOOH + (C4H8O)H Methyl ethyl ketone + butanals 73.065 3.48 2 1.56±2.45 1.51±0.44 0.86-2.53 0.38-0.81 Calibra + (C6H6)H Benzene 79.054 1.97 1 0.
    [Show full text]
  • Studies on Photochemical Reactions of Simple Alkenes
    Title STUDIES ON PHOTOCHEMICAL REACTIONS OF SIMPLE ALKENES Author(s) 井上, 佳久 Citation Issue Date Text Version ETD URL http://hdl.handle.net/11094/1547 DOI rights Note Osaka University Knowledge Archive : OUKA https://ir.library.osaka-u.ac.jp/ Osaka University STUDIESON PHOTOCHEMICAL REACTIONS CF SIMPLE ALKENES YOSHIHISA INOUE OSAKA UNIVERSITY OSAKA, JAPAN JANUARY, 1977 ii Preface The work of thi's•theSis 'was performed under the guiqance of Professor Hiroshi Sakurai at the ZnstituteofScientific and lndustrial Research, Osaka University. I arn deeply grateÅíul to Professor Hiroshi Sakurai for his appro- priate guidance and continuOus encouragernent throughout this work since 1972. : am aiso grateful to Professor Yoshinobu Odaira-who initiated me into the organic photochemistry in 1971-1972. : arn indebted to Assistant Professor Setsuo Takamuku for his invaluable discussions throughout the work. Many thanks are given to Drs. Yoshiki Okarrtoto, Chyongjin Pac, Susumu Toki, and Yasuo Shige- mitsu for their helpful suggestions through the stimulating discussions with me. T would like to express my gratitude to Mr. Kazuyoshi Mori- tsugut Mr. Masahiro Kadohira, and Ms. Yoko Kunitomi for their collabo- rations in the course of experiment. Finally I wish to thank all the members of Sakurai Laboratory for their warm friendship. t- ..<2IZI Yoshihisa Inoue Suita, Osaka January, Z977 iii List of Papers The contents of this thesis are composed of the following papers. 1) Mercury Photosensitized Rbaction of Cycloheptene. Mechanism of Norcarane Formation Y. Tnoue, M. Kadohira, S. Takasnuku, and H. Sakurait Tetrahedron Lett., 459(1974). 2) Vapor-phase Photolysis of cis-- and trans-4i5-Diraethylcyclohexenes Y. rnoue, S.
    [Show full text]
  • United States Patent Office
    3,258,488 United States Patent Office Patented June 28, 1966 2 ether, xylene, toluene, tetralin, cumene and tetrahydro 3,258,488 DIBENZOADCYCLOHEPTENEDERIVATIVES furan, and compatible mixtures of such solvents. The Claude I. Judd, Mequon, and Alexander E. Drukker and reaction can be effected at room temperature or elevated John H. Biel, Milwaukee, Wis., assignors to Colgate temperatures, depending on the reactivity of the alkali Palmolive Company, a corporation of Delaware metal compound used in the process. The reaction is No Drawing. Filed Aug. 12, 1963, Ser. No. 301,658 substantially complete in 1 to 4 hours. Following ter 3 Claims. (C. 260-570.8) mination of the reaction the product can be isolated, if desired, but this is ordinarily not done since it can be This is a continuation-in-part of abandoned application used as present in the reaction mixture in the next step. Serial No. 21,610 filed April 12, 1960. 10 Reaction between the alkali metal salt of 5H-dibenzo This invention relates to novel chemical compounds ad-cycloheptene and the disubstituted aminoalkyl ha and processes of preparing the same. More particularly, lide can be effected by bringing the reactants together in a this invention is concerned with novel basic dibenZSu suitable inert high boiling liquid reaction medium such berene derivatives and processes of producing such com as dioxane, toluene, Xylene, ethyl ether, tetralin, cumene pounds. and tetrahydrofuran. The reaction mixture from the According to the present invention there are provided formation of the alkali metal 5H-dibenzo(a,d)-cyclo novel basic 5H-dibenzoad-cycloheptene derivatives of heptene can be used as the reactant and solvent source the formula to which the appropriate aminoalkyl halide reactant can be added.
    [Show full text]
  • Palladium-Catalyzed Arylation and Vinylation of Cyclic Alkenes William H
    Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1990 Palladium-catalyzed arylation and vinylation of cyclic alkenes William H. Gong Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Gong, William H., "Palladium-catalyzed arylation and vinylation of cyclic alkenes " (1990). Retrospective Theses and Dissertations. 9372. https://lib.dr.iastate.edu/rtd/9372 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Retrospective Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. INFORMATION TO USERS The most advanced technology has been used to photograph and reproduce this manuscript from the microfilm master. UMI films the text directly from the original or copy submitted. Thus, some thesis and dissertation copies are in typewriter face, while others may be from any type of computer printer. The quality of this reproduction is dependent upon the quality of the copy submitted. Broken or indistinct print, colored or poor quality illustrations and photographs, print bleedthrough, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send UMI a complete manuscript and there are missing pages, these will be noted. Also, if unauthorized copyright material had to be removed, a note will indicate the deletion. Oversize materials (e.g., maps, drawings, charts) are reproduced by sectioning the original, beginning at the upper left-hand corner and continuing from left to right in equal sections with small overlaps.
    [Show full text]
  • II. Nomenclature Rules for Alkenes 1. the Parent Name Will Be the Longest
    1 Lecture 9 II. Nomenclature Rules For Alkenes 1. The parent name will be the longest carbon chain that contains both carbons of the double bond. Drop the -ane suffix of the alkane name and add the –ene suffix. Never name the double bond as a prefix. If a double bond is present, you have an alkene, not an alkane. alkane + -ene = alkene 2. Begin numbering the chain at the end nearest the double bond. Always number through the double bond and identify its position in the longest chain with the lower number. In the older IUPAC rules the number for the double bond was placed in front of the stem name with a hyphen. Under the newer rules, the number for the double bond is placed right in front of “ene”, with hyphens. We will use the newer rules for specifying the location of pi bonds. 1 2 3456 H3CCHCH CH 2 CH2 CH3 hex-2-ene (newer rules) 2-hexene (older rules) 3. Indicate the position of any substituent group by the number of the carbon atom in the parent (longest) chain to which it is attached. CH 1 2 345 3 H3CCHCHCHCH2 CH CH3 6 7 CH3 Numbering is determined by the double bond, not the branches, because the double bond has 5,6-dimethylhept-3-ene (newer rules) higher priority than any alkyl branch. 5,6-dimethyl-3-heptene (older rules) 4. Number cycloalkenes so that the double bond is 1,2 (number through the double bond). Number in the direction about the ring so that the lowest number is used at the first point of difference.
    [Show full text]
  • Palladium‑Catalyzed Alkylation of Alkenes Using Epoxides. Part II: Palladium‑Catalyzed Asymmetric Wacker‑Type Anti‑Attack of Alkenes
    This document is downloaded from DR‑NTU (https://dr.ntu.edu.sg) Nanyang Technological University, Singapore. Part I: Palladium‑catalyzed alkylation of alkenes using epoxides. Part II: Palladium‑catalyzed asymmetric wacker‑type anti‑attack of alkenes Teng, Shenghan 2020 Teng, S. (2020). Part I: Palladium‑catalyzed alkylation of alkenes using epoxides. Part II: Palladium‑catalyzed asymmetric wacker‑type anti‑attack of alkenes. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/146048 https://doi.org/10.32657/10356/146048 This work is licensed under a Creative Commons Attribution‑NonCommercial 4.0 International License (CC BY‑NC 4.0). Downloaded on 08 Oct 2021 15:05:54 SGT PART I: PALLADIUM-CATALYZED ALKYLATION OF ALKENES USING EPOXIDES PART II: PALLADIUM-CATALYZED ASYMMETRIC WACKER-TYPE ANTI-ATTACK OF ALKENES TENG SHENGHAN SCHOOL OF PHYSICAL AND MATHEMATICAL SCIENCES 2020 PART I: PALLADIUM-CATALYZED ALKYLATION OF ALKENES USING EPOXIDES PART II: PALLADIUM-CATALYZED ASYMMETRIC WACKER-TYPE ANTI-ATTACK OF ALKENES TENG SHENGHAN SCHOOL OF PHYSICAL AND MATHEMATICAL SCIENCES A thesis submitted to the Nanyang Technological University in partial fulfilment of the requirement for the degree of Doctor of Philosophy 2020 Statement of Originality I hereby certify that the work embodied in this thesis is the result of original research done by me except where otherwise stated in this thesis. The thesis work has not been submitted for a degree or professional qualification to any other university or institution. I declare that this thesis is written by myself and is free of plagiarism and of sufficient grammatical clarity to be examined. I confirm that the investigations were conducted in accord with the ethics policies and integrity standards of Nanyang Technological University and that the research data are presented honestly and without prejudice.
    [Show full text]