DOCSLIB.ORG

Mogratory Abilities of Beta-Heteroatomic Substituents to Divalent Carbon

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Mogratory Abilities of Beta-Heteroatomic Substituents to Divalent Carbon This dissertation has been microfilmed exactly as received 68-8871 ROBSON, John Howard, 1940- MIGRATORY ABILITIES OF fi -HETEROATOMIC SUBSTITUENTS TO DIVALENT CARBON. The Ohio State University, Ph.D., 1967 Chemistry, organic University Microfilms, Inc., Ann Arbor, Michigan MIGRATORY ABILITIES OF p-HETEROATOMIC SUBSTITUENTS TO DIVALENT CARBON DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By John Howard Robson, B.S. ****** The Ohio State University 1967 Approved by Department of Chemistry Dedicated to my wife, Diane ii ACKNOWLEDGMENTS I wish to express my gratitude to Professor Harold Shechter for his inception of this study and for his masterful help in the preparation of this manuscript. Dr. Shechter*s devotion to chemistry and professional character are qualities that have been most inspiring. I am grateful to the Chemistry Department of The Ohio State University, the Department of Navy, the National Institute of Health, and the National Science Poundation for financial assistance. I wish to thank: my parents, wife, and family for their sacrifices, interest and encouragement which enabled my pur­ suit of a formal education. iii VITA July 26, 194-0 Born - East Liberty, Ohio 1962 .................... B.S., Ohio Northern University Ada, Ohio 1962-1964 ............... Teaching Assistant, Department of Chemistry, The Ohio State University, Columbus, Ohio 1964-1967 ............... research Associate, Department of Chemistry, The Ohio State University, Columbus, Ohio iv CONTENTS Page ACKNOWLEDGMENTS iii VITA iv TABLES viii INTRODUCTION 1 HISTORICAL DISCUSSION 18 EXPERIMENTAL 51 General Information 51 Melting points Elemental analyses Infrared spectra Nuclear magnetic resonance spectra Mass spectra Gas chromatography Solvents Intermediates ...................... 53 Methoxyacetonitrile 2-Methoxyacetophenone 2-Methoxyacetophenone tosylhydrazone 2-Phenoxyacetophenone 2-Phenoxyacetophenone tosylhydrazone 2-Hydroxyacetophenone 2-Hydroxyacetoohenone tosylhydrazone 2-Dimethylaminoacetophenone 2-Dimethylaminoacetophenone hydrochloride tosylhydrazone 2-Phenylaminoacetophenone 2-Phenylaminoacetophenone tosylhydrazone 2-Phenylmercaptoacetophenone 2-?henylmereaptoacetophenone tosylhydrazone 2-Ethylmercaptoacetophenone 2-Ethylmercaptoacetophenone tosylhydraz one 2-£thylmerc spto-A1 -chloroacetophenone 2-Ethylmercapto-4-,~chloroacetophenone tosylhydrazone CONTENTS (Cont'd) Page 2-Ethylmercapto-4.,-broEoacetophenone . 61 2-Ethylm9rcaptO“^*-bromoacetophenone tosylhydrazone 2-Kethyl-l,3-dithiane 2-Lithio-2-methyl-l ,3-dithiane 2-Benzoyl-2-methyl-l ,3-dithiane 2-Benzoyl-2-rnethyl-1,3-dithiane tosylhydrazone 2-ForEyl-2-methyl-l ,3-dithisne 2-Forinyl-2-methyl-l ,3-dithiane tosylhydrazone Standards ..... .................. 2-Methoxy-2-phenylethyl iodide a-Methoxystyrene p-M ethoxystyrene cis- and trans-g-Methoxystyrene p-Phenoxystyrene p-Phenylmercaptostyrene p-Ethylmercaptostyrene Decomposition of 2-methoxyacetophenone tosylhydrazone ......... 70 Decomposition of 2-phenoxyacetophenone tosylhydrazone.......................... 74- Decomposition of 2-hydroxyacetophenone tosylhydrazone......................... 76 Decomposition of 2-dimethylaminoaceto- phenone hydrochloride tosylhydrazone .... 77 Decomposition of 2-phenylaminoaceto- phenone tosylhydrazone .................. 79 Decomposition of 2-phenylmercaptoaceto- phenone tosylhydrazone .................. 79 Decomposition of 2-ethylmercaptoacetophenone tosylhydrazone................ 81 Decomposition of 2-ethylmercapto-4-1- chloroacetophenone tosylhydrazone ....... 82 vi CONTENTS (Cont’d) » Page Decomposition of 2-ethylmercapto-4'- bromoacetophenone tosylhydrazone ........... 83 Base-catalyzed thermolysis of 2-pbenyl- mercaptoacetophenone tosylhydrazone in different environments ................. 84 Decomposition of 2-ethylmercaptoaceto- phenone tosylhydrazone by various bases in different environments ........... 85 Reaction of 2-ethylmercaptoacetophenone tosylhydrazone with 3 equivalents of n-butyllithium .......................... 88 Kinetic study of the thermal decomposition of 1-diazo-l-phenylethane................. 91 Kinetic study of the thermal decomposition of l-diazo-2-ethylmercapto- 1-phenylethane ..... ................. 91 Decomposition of 2-benzoyl-2-methyl-l,3- dithiane tosylhydrazone ................... 92 Decomposition of 2-formyl-2-methyl-l,3- dithiane tosylhydrazone ................... 93 APPENDIX I - Infrared Spectra ................ 95 (Figures 1-9) APPENDIX II - Nuclear Magnetic Resonance Spectra . 99 (Figures IO-15) APPENDIX III- Kinetic Plots ...................... 106 (Figures 16-19) vii TABLES Table Page 1. p-Toluenesul fonylhydrazor.es of 2-Substituted Acetophenones ............... 23 2. Base Decomposition of 2-Phenylmercapto- acetophonone Tosylhydrazone............... 86 3. Base-catalyzed Decomposition of 2-Sthyl- mercaptoacetophenone Tosylhydrazone ....... 87 viii INTRODUCTION In the past two decades there has been renewed interest in the chemistry of divalent carbon (l). Such intermediates are known (1) Divalent carbon intermediates in this discussion will be denoted by the general term "carbene." The simplest such inter­ mediate, sCH^ is called methylene; other carbenes are named by adding "-idene" to the name of the corresponding univalent radical. Other members of this homologous series thus are named ethylidene, CH^CH:; benzylidene, PhCH:; etc. [international Union of Pure and Applied Chemistry Report on Nomenclature, J. Am. Chem. Soc.. 82. 5545 (I960)]. as carbenes and contain carbon linked to two adjacent groups by covalent bonds, and possessing two nonbonding electrons which may have antiparallel spins (singlet state) or parallel spins (triplet state). The spin states of carbenes will be discussed in more detail later. The present investigation involves study of intramolecular rearrangement reactions of carbenic systems which allow possible participation of substituents containing electron-donor hetero atoms. The possible participating and rearranging groups of interest are covalent sulfur, oxygen, and nitrogen in positions beta to the divalent center (Equation 1). ? ♦ Z - C - C - -- : - C - C (1) I 1 Z = S, 0. and N, 1 2 The purposes of this study are: 1) to evaluate the migratory abilities of the possible participating hetero groups, 2) to study the effects of environment on the paths of decomposition of such diazo compounds, 3) to use hetero atom rearrangement as a synthetic tool, and 4) to compare the reaction patterns of these carbenic systems with those which occur by appropriately modified mechanisms. The experimental design of this study involves determination of the products of decomposition of selected diazo compounds ob­ tained pure or generated in situ (Equations 2, 3, and 4) by base- catalyzed thermal decompositions of their respective 2~toluenesulfonyl- hydrazones, a process known to proceed via a carbenic mechanism (2). (2) L. Friedman and H. Shechter, J. Am. Chem. Soc., 81, 5512 (1959). n-nhso2c7 h7 n2 :Z~CR2 - C - R - :Z-CR2 - C - R + 02SC?H7 + BH (2) N2 i :Z-CR2 - C - R --- * :Z - CR2 - C - R + K2 (3) :Z - CR2 - C - R --- * :Z - CR* = CR'R + R2C = RC-Z: (4) For determination of the migratory aptitudes appropriate 2-alkylhetero and 2-arylheteroacetophenone tosylhydrazones were 3 prepared and decomposed carbenically. Analysis of the decomposition products is by gas liquid chromatography. Base-catalyzed decomposition of the acetophenone tosyl- hydrazones with sodium methoxide, lithium methoxide, and n-butyl- lithium (1 .0 to 3*1 equivalents) were investigated in order to ascertain the influence of base strength, stoichiometry and various cations upon the carbenic rearrangement processes. A kinetic study of thermolysis of l-diazo-2-ethylmercapto-l- phenylethane and 1-diazo-l-phenylethane was made in order to determine the influence of participation in these decomposition systems. To further extend the study of possible hetero atom rearrangement to carbenic centers, an investigation of base- catalyzed thermal decomposition of l,3"dithiane tosylhydrazones was initiated (Equation 5) . N - NHSOgC^Hy © + N 2 + s o 2 C 7H 7 (5) HISTORICAL Attempts to prepare the simplest carbene, methylene (l), were (1) (a) J. B. Dumas, Ann. chlra. phys., [2], ^8, 28 (1865)* (b) H. V. Regnault, Ibid.[21. 71, -427 (1839). (e) A. Penot, Ann., 101, 375 (1857). (d) A. M. Butlerov, ibid.. 120. 356 (1861). made before the quadrivalency of carbon was established. These early synthetic failures were followed in the first decade of the twentieth century by postulation of carbenes as intermediates in many organic reactions. Methylene was suggested as a reaction intermediate in the photolysis of diazomethane (2) and also in the (2) T. Curtius, A. Darapsky, and E. Kflller, Chem. Ber., £1, 3168 (1908). formation of ethylene by hydrogenation of carbon monoxide over nickel or palladium (3). Early conclusions from work with ketenes (3) E. I. Orlov, Zh. Russk. Fiz. Khim. Obshch., AO, 1588 (1908). and diazo compounds suggested that carbenes are transient diradicals (A), but the observation (5,6) and adequate interpretation (6) of (A) H. Staudinger, E. Anthes, and F. Pfenniger, Ber. deut. chem. Ges., ££, 1928 (1916). A (5) H. Murwein, H. Rathjen, and H. Werner, ibid.. 71* 1610 (1942). (6) W. v. £. Doering, R. G. Buttery, R. G. Laughlin, and N.Chaudhuri, J. Am. Chem. Soc., 78, 3224 (1956). insertion of methylene and other divalent derivatives into carbon— hydrogen bonds made it clear
Load more

Recommended publications
  • Monoamine Oxydases Et Athérosclérose : Signalisation Mitogène Et Études in Vivo
    UNIVERSITE TOULOUSE III - PAUL SABATIER Sciences THESE Pour obtenir le grade de DOCTEUR DE L’UNIVERSITE TOULOUSE III Discipline : Innovation Pharmacologique Présentée et soutenue par : Christelle Coatrieux le 08 octobre 2007 Monoamine oxydases et athérosclérose : signalisation mitogène et études in vivo Jury Monsieur Luc Rochette Rapporteur Professeur, Université de Bourgogne, Dijon Monsieur Ramaroson Andriantsitohaina Rapporteur Directeur de Recherche, INSERM, Angers Monsieur Philippe Valet Président Professeur, Université Paul Sabatier, Toulouse III Madame Nathalie Augé Examinateur Chargé de Recherche, INSERM Monsieur Angelo Parini Directeur de Thèse Professeur, Université Paul Sabatier, Toulouse III INSERM, U858, équipes 6/10, Institut Louis Bugnard, CHU Rangueil, Toulouse Résumé Les espèces réactives de l’oxygène (EROs) sont impliquées dans l’activation de nombreuses voies de signalisation cellulaires, conduisant à différentes réponses comme la prolifération. Les EROs, à cause du stress oxydant qu’elles génèrent, sont impliquées dans de nombreuses pathologies, notamment l’athérosclérose. Les monoamine oxydases (MAOs) sont deux flavoenzymes responsables de la dégradation des catécholamines et des amines biogènes comme la sérotonine ; elles sont une source importante d’EROs. Il a été montré qu’elles peuvent être impliquées dans la prolifération cellulaire ou l’apoptose du fait du stress oxydant qu’elles génèrent. Ce travail de thèse a montré que la MAO-A, en dégradant son substrat (sérotonine ou tyramine), active une voie de signalisation mitogène particulière : la voie métalloprotéase- 2/sphingolipides (MMP2/sphingolipides), et contribue à la prolifération de cellules musculaire lisses vasculaires induite par ces monoamines. De plus, une étude complémentaire a confirmé l’importance des EROs comme stimulus mitogène (utilisation de peroxyde d’hydrogène exogène), et a décrit plus spécifiquement les étapes en amont de l’activation de MMP2, ainsi que l’activation par la MMP2 de la sphingomyélinase neutre (première enzyme de la cascade des sphingolipides).
    [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]
  • Synthesis of Hydrazide-Hydrazone Derivatives and Their Evaluation of Antidepressant, Sedative and Analgesic Agents R
    R M Mohareb et al, /J. Pharm. Sci. & Res. Vol.2(4), 2010, 185-196 Synthesis of hydrazide-hydrazone derivatives and their evaluation of antidepressant, sedative and analgesic agents 1,2 1 2 3 R. M. Mohareb , K. A. El-Sharkawy , M. M. Hussein and H. M. El-Sehrawi 1Faculty of Pharmacy, Organic Chemistry Department, October University for Modern Sciences and Arts (MSA) – El-Wahat Road – 6 October City – Egypt. 2Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt. 3Faculty of Pharmacy (Girls), Pharmaceutical Chemistry Department, Al-Azhar University, Nasr City, Cairo, A.R. Egypt. Abstract: The reaction of cyanoacetylhydrazine (1) with -bromo(4-methoxyacetophenone) (2) gave the hydrazide- hydrazone derivative 3. Compound 3 reacted with either potassium cyanide or potassium thiocyanide to give the cyanide or thiocyanide derivatives 4a or 4b respectively. The reaction of compound 3 with either hydrazine hydrate or phenylhydrazine gave the hydrazine derivatives 6a or 6b respectively. The latter compounds underwent a series of heterocyclization when react with different reagents to give 1,3,4-triazine and pyridine derivatives. The antidepressant, sedative and analgesic activities of the newly synthesized products were evaluated. Keywords: Antidepressant. hydrazide-hydrazone. pyridine. sedative. 1,3,4-triazine, Introduction: Micro Analytical Data Unit at Cairo We report here the synthesis of a series of University, Giza, Egypt. hydrazide-hydrzones via the reaction of Synthetic pathways are presented in cyanoacetylhydrazine 1 with -bromo(4- Schemes 1-2 and physicochemical, methoxyacetophenone) 2. The hydrazide- spectral data for the newly synthesized hydrazones have been demonstrated to compounds are given in Tables 1 and 2.
    [Show full text]
  • The. Reactions Op Semicarbazones, Thiosbmicarbazonbs
    THE. REACTIONS OP SEMICARBAZONES, THIOSBMICARBAZONBS AMD RELATED COMPOUNDS, IMCLTJDIMG THE ACTION OF AMINES ON AMINOCARBOCARBAZONES. A THESIS PRESENTED BY JOHN MCLEAN B.So. IN FULFILMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY OF THE UNIVERSITY OF GLASGOW. / MAY *936. THE ROYAL TECHNICAL COLLEGE, GLASGOW. ProQuest Number: 13905234 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a com plete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest ProQuest 13905234 Published by ProQuest LLC(2019). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States C ode Microform Edition © ProQuest LLC. ProQuest LLC. 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106- 1346 This research was carried out in the Royal Technical College, Glasgow, under the supervision of Professor F.J. Wilson, whose helpful advice was greatly appreciated by the author. CONTENTS. Page General Introduction, PART 1. The Action of Amines on Amino Carhocarbazones. Introduction... ..... ,..................... 4 Benzylamine......... Theoretical.............. 11 ......... Experimental............. 15 Aniline............. Theoretical............ 21 ............. Experimental............ 22 B-Naphthylamine..... Theoretical............... 27
    [Show full text]
  • Design and Biological Evaluation of Biphenyl-4-Carboxylic Acid Hydrazide-Hydrazone for Antimicrobial Activity
    Acta Poloniae Pharmaceutica ñ Drug Research, Vol. 67 No. 3 pp. 255ñ259, 2010 ISSN 0001-6837 Polish Pharmaceutical Society DESIGN AND BIOLOGICAL EVALUATION OF BIPHENYL-4-CARBOXYLIC ACID HYDRAZIDE-HYDRAZONE FOR ANTIMICROBIAL ACTIVITY AAKASH DEEP1*, SANDEEP JAIN2, PRABODH CHANDER SHARMA3 PRABHAKAR VERMA4, MAHESH KUMAR4, and CHANDER PARKASH DORA1 1Department of Pharmaceutical Sciences, G.V.M. College of Pharmacy, Sonepat-131001, India 2Department of Pharm. Sciences, Guru Jambheshwar University of Science and Technology, Hisar-125001, India 3Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136119, India 4Institute of Pharmaceutical Sciences, Maharishi Dayanand University, Rohtak-124001, India Abstract: Seven biphenyl-4-carboxylic acid hydrazide-hydrazones have been synthesized. These hydrazone derivatives were characterized by CHN analysis, IR, and 1H NMR spectral data. All the compounds were eval- uated for their in vitro antimicrobial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fun- gal strain Candida albicans and Aspergillus niger. All newly synthesized compounds exhibited promising results. Keywords: synthesis, hydrazide-hydrazones, antimicrobial activity Development of novel chemotherapeutic EXPERIMENTAL agents is an important and challenging task for the medicinal chemists and many research programs are Melting points were determined in open capil- directed towards the design and synthesis of new lary tubes and are uncorrected. Infra-red spectra drugs for their chemotherapeutic usage. Hydrazone were recorded on Perkin Elmer Spectrum RXI FTIR compounds constitute an important class for new spectrophotomer in KBr phase. 1H NMR spectra drug development in order to discover an effective were run on BRUKER spectrometer (300 MHz) compound against multidrug resistant microbial using TMS as an internal standard.
    [Show full text]
  • Silybum Marianum (Milk Thistle) Flower in Vitro and on Human Explants
    Molecules 2015, 20, 3549-3564; doi:10.3390/molecules20033549 OPEN ACCESS molecules ISSN 1420-3049 www.mdpi.com/journal/molecules Article Anti-Glycation Activities of Phenolic Constituents from Silybum marianum (Milk Thistle) Flower in Vitro and on Human Explants Seoungwoo Shin, Jung-A Lee, Minkyung Kim, Hyunwoo Kum, Eunsun Jung * and Deokhoon Park * Biospectrum Life Science Institute, Eines Platz 11th FL, 442-13 Sangdaewon Dong, Seoungnam City, Gyunggi Do 462-807, Korea; E-Mails: [email protected] (S.S.); [email protected] (J.-A.L.); [email protected] (M.K.); [email protected] (H.K.) * Authors to whom correspondence should be addressed; E-Mails: [email protected] (E.J.); [email protected] (D.P.); Tel.: +82-31-750-9400 (E.J. & D.P.); Fax: +82-31-750-9494 (E.J. & D.P.). Academic Editor: Derek J. McPhee Received: 25 November 2014 / Accepted: 15 February 2015 / Published: 19 February 2015 Abstract: Glycation is an ageing reaction of naturally occurring sugars with dermal proteins, with clinical signs appearing in vivo around age 30, and increasing steadily/regularly with age. The suppleness of the dermis is affected by the formation of bridges between proteins and sugars (Maillard’s reaction). The accumulation of advanced glycation end products (AGEs) in skin plays a very important role in skin ageing. Therefore, natural compounds or extracts that possess antiglycation activities may have great anti-ageing potential. In the present study, Silybum marianum flower extract (SMFE) was demonstrated to possess antiglycation activity. We found that SMFE inhibits glycation reaction between BSA and glucose. In addition, antiglycation activity of SMFE was confirmed in a human skin explants model.
    [Show full text]
  • Toxicological Profile for Hydrazines. US Department Of
    TOXICOLOGICAL PROFILE FOR HYDRAZINES U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES Public Health Service Agency for Toxic Substances and Disease Registry September 1997 HYDRAZINES 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. HYDRAZINES 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 HYDRAZINES vii CONTRIBUTORS CHEMICAL MANAGER(S)/AUTHOR(S): Gangadhar Choudhary, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Hugh IIansen, Ph.D. ATSDR, Division of Toxicology, Atlanta, GA Steve Donkin, Ph.D. Sciences International, Inc., Alexandria, VA Mr. Christopher Kirman Life Systems, Inc., Cleveland, OH THE PROFILE HAS UNDERGONE THE FOLLOWING ATSDR INTERNAL REVIEWS: 1 . Green Border Review. Green Border review assures the consistency with ATSDR policy. 2 . Health Effects Review. The Health Effects Review Committee examines the health effects chapter of each profile for consistency and accuracy in interpreting health effects and classifying end points. 3. Minimal Risk Level Review. The Minimal Risk Level Workgroup considers issues relevant to substance-specific minimal risk levels (MRLs), reviews the health effects database of each profile, and makes recommendations for derivation of MRLs. HYDRAZINES ix PEER REVIEW A peer review panel was assembled for hydrazines. The panel consisted of the following members: 1. Dr.
    [Show full text]
  • Synthetic and Naturally Occurring Hydrazines As Possible Cancer Causative Agents
    [CANCER RESEARCH 35, 3693-3697 December 1975] Synthetic and Naturally Occurring Hydrazines as Possible Cancer Causative Agents Bela Toth' The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska 68105 SUMMARY SYNTHETIC HYDRAZINES The various synthetic substituted hydrazines, which cause tumors in animals, are briefly enumerated. To date, 19 of Studies on the carcinogenic potentialities of synthetic them have proved to be tumorigenic in animals. A number substituted hydrazines began in 1962, when it was shown of these chemicals are found today in the environment, in that the base compound hydrazine sulfate induced lung industry, in agriculture, and in medicine, and the human neoplasms in mice (1). Subsequently, a series of hydrazine population is exposed to a certain degree to some of them. derivatives were investigated in various laboratories for Hydrazine also occurs in nature in tobacco and tobacco tumor-inducing capabilities. These studies clearly demon smoke. The three other naturally occurring hydrazine strated that these chemicals are indeed powerful tumori compounds are N-methyl-N-formylhydrazine, which oc genic substances in mice, hamsters, and rats, due to their curs in the wild edible mushroom, Gyromitra esculenta, tumor-inducing abilities in the intestines, brain, lungs, and @-N-[―y-L(+)-glutamylJ-4-hydroxymethylphenyl blood vessels, liver, breasts, kidneys, etc. Now, we know of hydrazine and 4-hydroxymethylphenylhydrazine, whkh 19 hydrazine derivatives that have been shown to be tumor are found in the commonly eaten cultivated mushroom, inducers. These include, in addition to hydrazine (1, 32), Agaricus bisporus. Tumorigenesis studies with the natu methyl- (35, 40), 1,2-dimethyl- (6, 27, 36, 46, 52), 1,1- rally occurring hydrazines are in progress.
    [Show full text]
  • Synthesis, Characterization of New Hydrazone Derivatives Containing Heterocyclic Meioty Ahmed A
    Saheeb & Damdoom (2020): Synthesis and characterization of new hydrazine compound Oct 2020 Vol. 23 Issue 16 Synthesis, Characterization of new Hydrazone derivatives containing heterocyclic meioty Ahmed A. Saheeb1 and Wasan k.Damdoom2 1Col. of Agric. , University of Summer , Iraq. 2Col. of pharmacy, National of Science and Technology, Thi-Qar, Iraq. *Corresponding author: [email protected], [email protected] ( Damdoom) Abstract The present work includes synthesis and characterization of new hydrazine, compound (F1) derived from ethyl benzoate. Firstly, benzoate hydrazide [A1] has been synthesized from the condensation of ethyl benzoate with hydrazine. Then the benzoate hydrazide was reacted with phenylisothiocynate to prepare [B1]. Cyclization reaction of product [B1] with sodium hydroxide produced terazole derivative [C1].On the other hand, alkylation reaction of compound [C1] with chloroethylacetate in the presence of Sodium acetatetrihydrate as a catalyst resulted [D]. The acid hydrazide derivative [E1] has been synthesized by the reaction of compound [D1] with hydrazine hydrate. Finally, hydrazone derived [F1] was synthesized by the condensation reaction of the acid hydrazide [E1] with isatin. The synthesized compound was characterized by, FT-IR, 1H-NMR, 13C-NMR and Mass spectra. Compound (F2) derived from Methyl-4-hydroxybenzoate react with ethylchloroacetate ton prepare (A2) this compound react with hydrazine by reflux and used ethanol as as asolvent to give (B2). The hyrazone [C2] was synthesized by the condensation of 4-(2-hydrazino-2-oxoethoxy) benzohydrazide, and add 5 drops of acetic acid. Then the mixture refluxed for 8 hours (monitored by TLC). The hydrazone was precipitated, filtered and recrystallized from ethanol) to get white solid.
    [Show full text]
  • Receptor Antagonist
    Europäisches Patentamt *EP001604983A1* (19) European Patent Office Office européen des brevets (11) EP 1 604 983 A1 (12) EUROPEAN PATENT APPLICATION published in accordance with Art. 158(3) EPC (43) Date of publication: (51) Int Cl.7: C07D 217/26, C07D 403/06, 14.12.2005 Bulletin 2005/50 C07D 403/12, C07D 491/113, A61K 31/472, A61K 31/4741, (21) Application number: 04721010.9 A61P 43/00, A61P 29/00, (22) Date of filing: 16.03.2004 A61P 35/00, A61P 15/00, A61P 15/08, A61P 15/10, A61P 15/14, A61P 37/00, A61P 5/48, A61P 3/10, A61P 3/02, A61P 3/06, A61P 17/00, A61P 19/02, A61P 19/08 (86) International application number: PCT/JP2004/003496 (87) International publication number: WO 2004/083184 (30.09.2004 Gazette 2004/40) (84) Designated Contracting States: • HINUMA, Shuji AT BE BG CH CY CZ DE DK EE ES FI FR GB GR Tsukuba-shi, Ibaraki 3050821 (JP) HU IE IT LI LU MC NL PL PT RO SE SI SK TR • KANZAKI, Naoyuki, c/o Takeda Pharmaceutical Designated Extension States: Yodogawa-ku, Osaka-shi, Osaka (JP) AL LT LV MK • BANNO, Yoshihiro, c/o Takeda Pharmaceutical Yodogawa-ku, Osaka-shi, Osaka (JP) (30) Priority: 17.03.2003 JP 2003072709 • YOSHIDA, Hiromi Yuki-gun, Ibar aki 3002741 (JP) (71) Applicant: Takeda Pharmaceutical Company • MATSUMOTO, Hirokazu Limited Tsukuba-shi, Ibaraki 3050821 (JP) Osaka 541-0045 (JP) (74) Representative: Rickard, Timothy Mark Adrian (72) Inventors: Takeda Euro IP Department, • ITOH, Fumio 11-12 Charles II Street Tsukuba-shi, Ibaraki 3050821 (JP) London SW1Y 4QU (GB) (54) RECEPTOR ANTAGONIST (57) A compound represented by
    [Show full text]
  • Synthesis of 1,1-Dialkyhydrazines and Their Hydroxyl Radical Degradation in Aqueous Environments
    Western Michigan University ScholarWorks at WMU Master's Theses Graduate College 8-2012 Synthesis of 1,1-Dialkyhydrazines and their Hydroxyl Radical Degradation in Aqueous Environments Benjamin F. Strong Follow this and additional works at: https://scholarworks.wmich.edu/masters_theses Part of the Environmental Chemistry Commons Recommended Citation Strong, Benjamin F., "Synthesis of 1,1-Dialkyhydrazines and their Hydroxyl Radical Degradation in Aqueous Environments" (2012). Master's Theses. 33. https://scholarworks.wmich.edu/masters_theses/33 This Masters Thesis-Open Access is brought to you for free and open access by the Graduate College at ScholarWorks at WMU. It has been accepted for inclusion in Master's Theses by an authorized administrator of ScholarWorks at WMU. For more information, please contact [email protected]. SYNTHESIS OF 1,1-DIALKYLHYDRAZINES AND THEIR HYDROXYL RADICAL DEGRADATION IN AQUEOUS ENVIRONMENTS by Benjamin F. Strong A Thesis Submitted to the Faculty ofthe Graduate College in partial fullilment ofthe requirements for the Degree ofMaster of Science Department ofChemistry Advisor: James J. Kiddle, Ph.D. Western Michigan University Kalamazoo, Michigan August 2012 THE GRADUATE COLLEGE WESTERN MICHIGAN UNIVERSITY KALAMAZOO, MICHIGAN Date June 21, 2012 WE HEREBY APPROVE THE THESIS SUBMITTED BY Benjamin F. Strong ENTITLED Synthesis of 1,1-dialkylhydrazines and their Hydroxyl Radical Degradation in Aqueous Environments AS PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE Master of Science DEGREE OF Chemistry (Department) James J. Kiddle Thesis Committee Chair Chemistry Blht Q(m (Program) Elke Schitffers Thesis Committee Member \ Andre Venter Thesis Committee Member APPROVED Date AjQL<=k ?OiZ Dean of The Graduate College SYNTHESIS OF 1,1-DIALKYLHYDRAZINES AND THEIR HYDROXYL RADICAL DEGRADATION IN AQUEOUS ENVIRONMENTS Benjamin F.
    [Show full text]
  • Further Studies on the Allylic Diazene Rearrangement Maha Laxmi Shrestha University of Arkansas, Fayetteville
    University of Arkansas, Fayetteville ScholarWorks@UARK Theses and Dissertations 5-2013 Further Studies on the Allylic Diazene Rearrangement Maha Laxmi Shrestha University of Arkansas, Fayetteville Follow this and additional works at: http://scholarworks.uark.edu/etd Part of the Organic Chemistry Commons Recommended Citation Shrestha, Maha Laxmi, "Further Studies on the Allylic Diazene Rearrangement" (2013). Theses and Dissertations. 706. http://scholarworks.uark.edu/etd/706 This Dissertation is brought to you for free and open access by ScholarWorks@UARK. It has been accepted for inclusion in Theses and Dissertations by an authorized administrator of ScholarWorks@UARK. For more information, please contact [email protected], [email protected]. FURTHER STUDIES ON THE ALLYLIC DIAZENE REARRANGEMENT FURTHER STUDIES ON THE ALLYLIC DIAZENE REARRANGEMENT A dissertation submitted in partial fulfillment of the requirement for the degree of Doctor of Philosophy in Chemistry By Maha Laxmi Shrestha Pittsburg State University Master of Science in Chemistry, 2007 May 2013 University of Arkansas ABSTRACT Former graduate student Wei Qi and Professor Matt McIntosh have reported diastereoselective reductive 1,3-transpositions of acyclic α,β-unsaturated tosyl hydrazones to afford substrates with a 1,4-syn or 1,4-anti relationship between alkoxy and methyl groups that proceed via an ADR (Qi, W.; McIntosh, M. C. Org. Lett. 2008, 10, 357; Qi, W.; McIntosh, M. C. Tetrahedron 2008, 64, 7021). In these reports, silica gel was employed to accelerate the reduction. We have found that acetic acid gives the same results with high diastereoselectivity in the reaction. We further optimized the reaction by lowering the amount of catecholborane to 3 eq.
    [Show full text]