Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1947 Substituted pyridine and quinoline sulfides Mary Alys Plunkett Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Plunkett, Mary Alys, "Substituted pyridine and quinoline sulfides" (1947). Retrospective Theses and Dissertations. 15128. https://lib.dr.iastate.edu/rtd/15128 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 This manuscript has been reproduced 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 overiaps. ProQuest Information and Learning 300 North Zeeb Road, Ann Arbor, Ml 48106-1346 USA 800-521-0600 I NOTE TO USERS This reproduction is the best copy available. UMI' SUBSTITUTED PYRIDINE AND Q.UINOLINE SULFIDES by Mary Alys vPlunkett A Thesis Submitted to the Graduate Faculty for the Degree of DOCTOR OF PHILOSOPHX Major Subject: Organic Chemistry Approved: Signature was redacted for privacy. In Charge ^of Major VJ6yk. Signature was redacted for privacy. Head of'Major Department Signature was redacted for privacy. Iowa State College 1947 UMI Number: DP12913 . ® UMI UMI Microform DP12913 Copyright 2005 by ProQuest Information and Learning Company. All rights reserved. This microform edition is protected against unauthorized copying under Title 17, United States Code. ProQuest Information and Learning Company 300 North Zeeb Road P.O. Box 1346 Ann Arbor, Ml 48106-1346 QI)?4I. S3 11. •p 7 4s ackno?;lrdoment The author Is sincerely grateful to Dr. Henry Oilman for the encouragement, suggestions and helpful criticisms which he gave throughout the course of this investigation. T"f5'a7y Ill TABLE OF CONTENTS Page I. INTRODUCTION 1 II. HISTORICAL 5 A. Mercaptans 5 Creneral 5 Tertiary alkylamlnoalkyl mercaptans ... 10 Qulnollne merca^tanB 12 Pyridine mercaptans 13 B. Sulfides 15 General 15 Alkyl amlnoalkyl sulfides 16 Qulnollne sulfides 18 Pyridine sulfides 21 Hydroxy sulfides 23 C. Cheraotherapeutic Substances Used As a Basis for These Investlgr^^tlons. ... 23 D. Organosillcon Compounds 34 Nomenclature 34 A brief revle^' of organoslllcon chemistry. 35 III. EXPERIMENTAL 41 P-Dlethylamlnoethyl Mercaotan 41 ' Method A 41 Method B 41 Method C 42 V-Dlethylamlnopropyl Mercantan 42 Method A 42 Method B 43 2-Qulnolyl ^TDlethylaralnoethyl Sulfide Hydrochloride 44 2-Qulnolyl V-r)lethylaralnopror)yl Sulfide Hydrochloride 45 4-Methyl-2-qulnolyl P-Diethylaminoethyl Sulfide Dihydrochlorlde 46 4-Methyl-2-qulnolyl V-^le^bylamlnorirotiyl Sulfide T)1 hydro chloride 46 6-Mgthoxy-2~quInolyl D1ethylamInoethyl Sulfide Dlhydrochloride 47 Method A 47 Method B 48 8-Mercapto-6-methoxyaulnollne 49 Iv 4-Methyl-2-au1nolyl ^-(N-Plperldyl)ethyl Sulfide . 49 4-Methyl~2-qulnolyl ^-(N-Morphollno)ethyl Sulfide 50 6-Methoxy-4-raethyl-S-qulnolyl "V-^lethyl- amlnor>ror)yl Sulfide Hydrochloride . 51 Method A 51 Method B 52 4-Garboxy-2-qulnolyl i?-Dlethylamlnoethyl Sulfide Hydrochloride 52 N-Acetyllsatin 53 2-Hydroxyclnchonlnlc Acid 54 2-Chloroolnchonlnlc Acid 54 6-Methoxy-4-qulnolyl ^Dlethylamlnoethyl Sulfide Dlhydrochlorlde 55 7-Chloro-4-qulnolyl ^-Dlethylamlnoethyl Sulfide Dlhydrochlorlde 55 2-Q,ulnolyl ^-Hydroxy-V-mornhollnor)ror>yl Sulfide 56 2-Q,ulnolyl /^-Hydroxy-KmoiDhollnoioroTDyl Sul'flde PIcrate 57 2-Qulnolyl y^^droxy-V-nioi*DhollnoT)ror>yl Sulfide Dlhydrochlorlde 57 2-Qulnolyl /J-Hydroxy-V-DlperldylT^roTiyl Sulfide 58 2-Q,ulnolyl 2,4-Dlnltrot)henyl Sulfide .... 59 ri-Amlnothlophenol 59 2-Qulnolyl ^n-Amlnonhenyl Sulfide Hydro­ chloride 60 6-Methoxy-2-Q,ulnolyl Ti-Aralnonhenyl Sulfide . 61 6-Methoxy-2-aulnolyl T)-AralnoDhenyl Sulfide Hydrochloride 61 6-Methoxy-4-qulnolyl r>-kX[i\noT>laenyl Sulfide . 62 6-Methoxy~4-inethyl-2-qulnolyl Methyl Sulfide. 62 4-Carboxy-2-qulnolyl u-Aral not)hen yl Sulfide. 63 7-Chloro-4-qulnolyl 2-Renzlnildazole Sulfide Hydrochloride 64 7-Chloro-4-qutnolyl 2-( 4,5'-DlnhenyllmldazoTy]) Sulfide Dlhydrochlorlde 65 2-Q,ulnolyl 2-Thlazollnyl Sulfide Hydro­ chloride 66 7-Cliloro-4-qulnolyl rf-Dlethylamlnoethyl Sulfone Dlhy^drochlorlde 66 2-Merear)topyrldlne 67 2-PYrldyl 2,4-Dlnltror)henyl Sulfide 67 p_(jf-.Chloroethyl)pyrldlne Hydrochloride ... 68 p-(2-Pyrldyl)ethyl V-Dlethylamlnor)ror»yl Sulfide 69 V p-( 2-Pyriayl)ethyl ^Dlethylnmlnoethyl ' Sulfide . 70 Dltjhenylmethyl Mercaptan 71 TllT>henylmethyl 2-Pyridyl) ethyl Sulfide PI crate' 71 Method A 71 Method B 72 Diphenylmethyl 2-Pyrldyl)ethyl Sulfide HydroohJ.orlde 73 2-( r-GhloroT>rot)yl)r>yridlne Hydrochloride . 73 ^-(2-Pyrldyl) ethyl o-AralnoT>henyl Sulfide . 74 »-Dlethylamlnoetl^l )'-Dlethylamlnopro-nyl Sulfide D1hydrochloride 76 p-Dlethylamlnoethyl -(N-Pl-oerldyl)ethyl ' Sulfide ' 76 />~Plethylamlnoethyl ^'-(N-Mornhollno) ethyl ' Sulfide . 77 V-Dlethylamlnoprotiyl /3'-(N-Womhollno) ethyl Sulfide . 78 S-Benzothlazyl ^-Dlethylaralnoethyl Sulfide Hydrochloride 70 Dlphenylraethyl p-Amlnophenyl Sulfide Hydro­ chloride 79 V-(2-Plperldyl)propyl ji-Amlnonhenyl Sulfide D1 hydrochloride 80 2-Qulnolyl 2'-Pyrldyl Sulfide (attempted) . 81 Bi 8-(/3-d.l ethyl ami no ethyl) Disulfide Dlhydro- ' chloride 82 ^ P'ls-(4-methyl-g~aulnolyl) disulfide 82 ^Tflr)henyl(p-dlmethylarolnophenyl)sllane ... 83 A-Trlnhenyl(^-dimethylamlnoohenyl) sllajie 1-^dro chloride 84 'Diphenyl/di(r)-dlraethylamlno)phenyl7silane . 85 ^'Tetra(T)-dlme"^hylainlnonhenyl)sllane 85 i'^l(T)--dlm0thylainlnor)henyl)phenylsllane ... 86 WrlT)henyl( 2~thlenyl) Bllane 87 Trlphenyl^-(5-llthlo)thienyl/sllane .... 88 \3'rlphenyl'/^-( g* -qulnolyl)~2-thlenyl7Bllane. 88 /Triphenyl/5-(6'-methoxy-2'-^ulnolyl)-2- "; tTBlenyiysllane 89 tPrlphenyl/S-C 4"^, 7'-dichloro-2'-qulnolyl)- 2-thleny]L78ll«.n e 90 ,Trlmethyl(p-llthlor)henyl) silane 91 ^rimethyl/n-(2-qulnolyl) nhenylT^s 11 ane (At t eniT^ ted) ............. 92 ¥rlphGnyl(phenylethynyl)ellane 92 vl Reaction of jD-Dlmethylamlnonhenylllthlum with Silicon Tetrachloride 94 Reaction of P-Dlmethylaminonhenyllithlum with Kthyl Silicate 95 Di(T2-T)lmethylttmlnophenyl)cilethoxysllane. ... 96 RRactlon of p-DimethylaminoT)henyillthlum with Sllicochlorofonn 96 Hydrolysis of Trl(Ti-dimethylamlnor>henyl)- ethoxysllane 98 Hydrolysis of Dl(jD-dlmethylamlnor>henyl)- dlethoxysllane 99 Hex a(JO-dimethyl ami noT)henyl)dl sll oxane (Attemoted) 100 IV. DISCUSSION 102 A. Quinollne Sul-fldea 102 B. Hydroxy Sulfides 110 C. Pyridine Sulfides Ill D. p-AmlnoDhenyl Sulfides ..... 112 E. Miscellaneous Sulfides 116 Benadryl types 116 Alkylamlnoalkyl sulfides 118 F. Organoslllcon Oomt^ounde 120 V. SUMtiARY 125 1 I. IITTRODUCTIOH The study of stilfur compounds represents a relatively neglected pare of organic chomistry. In at least two direc­ tions its importance has, in the last fev; years, become felt more and more strongly - the field of industry and the field of pharmaceutical and biochemical research and chemotherapy. The triuniph of chemotherapy may bo said to date bade to 1910 when Erhlich discovered Salvai'^son as a cui'o for syphilis. From 1910 on rapid sta^idos were made in chemotherapyj but, until 1955, practically all of the successful chemical sub­ stances in uso v/ere remedies for tropical diseases caused by protozoa. It v;as not xmtil 1935, with the use of sulfanil- ainide, that the first of a series of substances was used which was effective against bacteria - the bacteria which give rise to the commonest diseases. The synthesis of qixi- nine Itself, for years a stumbling block to organic chemists, was accomplished by V/oodv;ard and Itoering in 1945.^ Chemists have for a very long time tried to find some definite relationship between chemical constitution and physiological activity so that thoy might use this Imowlodge In the preparation of new compoiands thiit raij;;lit have some value as therapeutic agents. In 1860 Cruni Brown and Tl Woodward ai-\d Dooring, J. i^. Chem. Soc., 67, 860 (1945). Fraaor showed that by a sllglit and constant chemical chanr-o, tertiary bases oi' widely difforlnc ph3''slolor;ical activities could be convez^ted to quaternary bases of almost vmlform activity. This fact led jjeoiole to believe that a cheraothorax->e\T.tic inillenniura was at hand, and that by skill­ ful prediction, the properties of a nev/ therapeutic sub­ stance cotild be ascertained from an inspection of its chemical formula. Thirty years after ( In 1901 ) Sir F. G. 3 Hopkins cominentod thtxs: Striking enou^-h has been the increase in the n\iiuber of Iraportant druca since the researches re­ ferred to were carried out, and it cannot be denied that the soai'ch for these drti^s has boon {^reatly aided by the knov/ledcc of the kind just discussed; but it is a matter for disappointment and perhaps for surprise tioat we should, today, after thirty years, be able to po3.nt to very few general relations bearing the stamp of such definiteness and simpli­ city as are found in the ease brought to liglit by Crum Bvoxm and Fraser; and oven now the results obtained by these investigators may be quoted as the most satisfactory instance to hand of obvious rela­ tion between chemical constitution and physiological action.