Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1944 Organoantimony compounds containing water- solubilizing groups Gordon James O'Donnell Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation O'Donnell, Gordon James, "Organoantimony compounds containing water-solubilizing groups " (1944). Retrospective Theses and Dissertations. 13752. https://lib.dr.iastate.edu/rtd/13752 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]. NOTE TO USERS This reproduction is the best copy available. UMI ORGANOANTHONX CaiPOUNDS CONTAINING WATi^E-SOLUBILIZING aE0UP3 by G-ordon J» O'Donnell A Thesis Sulanltted to the Graduate Faculty tor the Degree of DOCTOR OF PHILOSOPHIC Major Subject: Organic Chemistry Approved; Signature was redacted for privacy. Signature was redacted for privacy. Head of/Major Bepar^ment Signature was redacted for privacy. Dean of Graduate College Iowa State Golleg# 1944 UMI Number: DP12886 INFORMATION TO USERS 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 bleed-through, substandard margins, and improper alignment can adversely affect reproduction. In the unlikely event that the author did not send 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. UMI UMI Microform DP12886 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 -11- D ^ AGKN0\tLED(SiE8T The author wishes to express his sincere appreciation to Dr. Henry Crllman for the assist­ ance, encouragement and criticism given during this woric. -lil- TABLS OF CONTENTS Page IHTRODUGTION ... 1 HISTORICAL . 4 Introawctlon ...... 4 Trialkylantlraony Compounds ..... 12 Properties ..... 12 Preparation . 12 Trlaryl- and Dlarylalkylantlmony Compounds ... 18 Properties 18 Preparation ..... 22 Heterocyclic Antimony Gompoimds 27 Properties 27 Preparation . ......... 28 Ble(dlalkylantimony) Compoimds 29 Properties 29 Preparation 30 BlsCar^lantisony) 31 Properties 31 Preparation * 32 Bis(diarylantimony) 35 Properties 35 Preparation . 35 Tetraalkyl- end Trielkylarylstibonlusn Compounds . 36 Properties ..... 36 Preparation * 37 Tetraaryistlljonliffli Compoimds 40 Properties 40 Preparation 40 Trlvalent Aliphatic Antimony Compounds ..... 42 Properties 42 Preparation ..... ... 43 Pentaval^t Aliphatic Antimony Compounds .... 46 Properties 46 Preparation 50 Trlvalent Aromatic Antimony Compounds 56 Properties ... ...... 56 Preparation . 58 Pentavalent Aromatic Antimony Compounds ..... 68 Properties . ......... 68 Preparation ***.... .... 71 Aroaatic Stibonic Acids ..... 79 PiKsperties 79 Preparation 87 -iv- Page Dl~ and Trlstlbonic Aoida 100 Properties 100 Preparation .... ....... 100 Stlbonic Acids 103 Properties .... ....... 103 Preparation 104 Analytical Procedures for the Determination of Antimony ........ .... 107 Qualitative analysis ............ 107 Quantitative analysis * . 107 Biological Application of Organoantimony Com­ pounds . 109 Organoantimony therapy * . 109 Physiological action of antiiaony Ill Summaxy 112 Bibliography 113 EXPERIMEKTAL 129 Triarylantimony Conpoimds and Their Derivatives . 129 Preparation of Diphenylantimony Chloride .... 131 Preparation of Tri8(m-trifluoromethylphenyl)- antimony ...7 131 Preparation of DiphenyK^-trlfluoroiaethylphenyl)- antifflony . 133 Preparation of Trl-jg-brcwBophenylsiitiiaony .... 134 Preparation of Tri-p-bromophenylantimony Dichloride ................. 135 Preparation of Trl-p-bromophenylantimony Prom Tri-p-bromophesffylantlniony Dichloride .... 135 AttemptedHPreparatlon of Tri-p-broraophenylanti- mony Dlthioglycoll ate 136 Attempted Preparation of Tri-p-carboxyphenyl- antiraony 137 Preparation of Tri-4~dibensofuiylantimony .... 137 Attempted Preparation of Tri-2-pyridylantlBiony . 138 Preparation of Trls{p-diethylamlnophenyl>antimony 140 Attempted Preparation of Trl-p-hydroxyphenylantl- mony Dichloride 141 Attempted Preparation of Trl-o-hydroxyphenyl- antlmony 142 Preparation of p-(2,5-Dlfflethylpyrryl-l-phenyl)- dlphenylanTimony .............. 142 Preparation of Trls{p-2,5-dlraethylpyrryl-l- phenyl)antimony"' .............. 144 Preparation of Diphenyl(2-dlben20furyl)antimony . 145 Preparation of Tricetylantimony 146 Preparation of Diphenylantimony Saccharide . 147 Page Prsparatlon of Trlphenylantiaony Dlchlorid© via the Dia.zonium Salt ........... 148 Attempted Preparation of Tri-p-carboxyphenyl~ antioony Bichloride . 149 Attempted Preparation of Tri-jg- and Tri-a- carboxyphsnylantimony Diohloride 150 Attempted Preparation of Tri-^ and Tri-£- hydroxyphenylantifflony Bichloride 150 Aromatic stilKjnic acids .......... 151 Preparation of m-Trifluororaethylbenzenestibonic Acid 152 Method I 152 Method II 153 Method III ... 153 Method IV 153 Method V 154 Attempted Preparation of o-(2,5-Dimethylpyrryl-l)- benzenestibonio Acid~ ..... 155 Preparation of 4-Hitronaphthalene-l-stibonio Acid 156 Attempted Preparation of 2-Nitronaphthalene-l- etibonic Acid ....... 157 Attempted Preparation of 2(4'-SulfaiBylphenyl)- bsnzenestibonic Acid . ..... 158 Attempted Preparation of 4(4'-Siilfamylphenyl)- benzenestibonic Acid ............ 159 Preparation of Anthraquinone-l-stibonlc Acid . 159 Atteiapted Preparation of Anthraquinone-2-stibonio Acid .................... 161 Attempted Preparation of 3-Cerbazolestibonio Acid 161 Atteiapted Preparation of S-Phenanthreneatibonic Acid 162 Attempted Preparation of Dibenzofuran-3-stibonic Aoid 163 Attempted Preparation of N-Ethylcarbazole-'3- stibonic Acid 164 Preparation of 2-Phenylbenzoxazole-6-stibonic Acid ............. 164 Preparation of 2-Phenylbenzothiazole-6-stib(Miic Acid 166 Attempted Preparation of Benzothiazole-2-8tibonio Acid 167 Attempted Preparation of 4,4'-Distibonodiphenyl- sulfone .......... 168 Attempted Preparation of Diphenylsulfone-4- stibonic Aoid 169 Attempted Preparation of 3,5-Dimethylpyrazole-4- stibonic Acid . 171 -vi- ZSEt PrepE2?ation of the Thallluo Salt of Benzenestl- bonlc Acid 171 Attempted Stibonation of Resorcinol 172 Preparation of Benzeaestlbonic Acid by Decompo­ sition of the Double-salt in Alcohol .... 173 DISCUSSION OF RESULTS , . 175 frlvalent Oi^anoantlraony Compounds 175 Aromatic Stibonlo Acids 184 msmm * i89 APPENDIX ......... ..... 4 . 190 -vli- INDEX OF TABLES Page TABLE I TRIALKYLANTIMONX COMPOUNDS . • 17 TASLS II TRIARYL- AiJD DIARYLALKYLAI^TIMONY COMPOmiDS -• « 25 TABLE III BIS(ARYLAMTIMONY) COMPOUNDS • • » • 34 TABLE IV BIS(DIARYLAi;TI:iONY) GCLIPOUIIDS ....... m 36 TAH.S V TETRAALKYL- Al^ID TRIALKYLAiriLSTIBOKIlBI C0I,IPCUKD8 39 45 TAM^S VI TRIVALEHT aliphatic Ai-JTIUOKY COMPOUNDS • • • • 53 TABLE VII PiiNTAYALENT ALIPHATIC AIITIMONY CCXlPOiaiDS • • « 62 TABLE VIII TRIYALENT AROMATIC ANTBIONX COI.IPOUNDS . • 74 TAH.S IX PENTAV.4LENT AR^ATIC ANTIMONY COMPOUNDS « . • 92 TABLS X STIBOKIC ACIDS TABLE XI DI- AND TRI8TIB0WIC ACIDS ......... 102 TABLE XII 106 INTRODUCTION The use of antimony compounds In therapy has been knoisn since earliest tlmea. However, it was not until the middle of the nineteenth century, when Lowlg and Soh^elaer (163) first reported the synthesis of trlethylantlmony, that organoantisony compounds were available for chemotherapy. The instability and spontaneous inflaramablllty of the trialfcylantlmony compounds Halted investigation in this field until 1882, when Michaelis ana. Reese (176) found that broraobenzene and antimony trichloride reacted in the presence of sodlua to form triphenylantlsony. The most fruitful discovery in the history of organoanti- mony compounds was the disclosure of Hans Schmidt (229), wording in the laboratories of the Cheraische Pabrik von Heyden, that sroraatic stlbonic acids may be obtained from dlazoniura compounds by treatment with sodium antlraonite. The number of stlbonic acids which may be prepared by this reaction is praotically un­ limited, It Is aaong the stlbonic acids that the most active cheniotherapeutic agents have been found, Caronia (35) first successfully used such a derivative, the sodium salt of 4.aQe't;a« raidobenzenestibonlc acid. The similarity of antimony to arsenic led several investi­ gators to si^gest the use of antimony compounds in the treat­ ment of those diseases helped by arsenlcals. Much of the im­ petus given to the esperiments with antimonlals can be aoaredited -2- to the discovery of Plimmer and Thomsen (217) that the in­ jection of tartar emetic into mice which were higiily infected with trypanosomiasis, caused the parasites to disappear ^ith great repidity from the peripheral blood. The field of therapy has widened until now oi^anoantimony compounds are administered with varying degrees of success in the treataent of African trypenoBoraiasis, leishmaniasis, schistosomiasis, granuloma venereum, bilh-^rziosis, beri-beri, and syphilis. In the case of