Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1929 Organolead compounds Jack D. Robinson Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Robinson, Jack D., "Organolead compounds" (1929). Retrospective Theses and Dissertations. 14287. https://lib.dr.iastate.edu/rtd/14287 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. DM! films the text directly from the original or copy submitted. 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UMI' ORQ&mmAD Gommms S&dk D, Hoblnscn A Hiiesis SoSsmitted to tbe Gi^adaate Faculty for tlae Degree of DOCTOR OF PHILOSOPHS: Hajop Subject Organic Clienjistry Signature was redacted for privacy. In charge of ^ior work Signature was redacted for privacy. EeaS^^jor ^part^n^ Signature was redacted for privacy. Sean of (^?actu&ie College. loffa State College 1929 UMI Number; DP14534 UMI® UMI Microform DP14534 Copyright 2006 by ProQuest Information and teaming 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 AG001I7LEDG2SEM? 2516 writer wislies to express Ms appreciation to Dr, Henry Gil man for the suggestion of these problems and for Ms generous advice and encouragement given during the wrk. iThe author takes tMs occasion to express Ms indebt­ edness to Dr. 0« R. Sweeney under whose direction a portio of tMs work was done. - 3 - i a?ABLE OP COHOJEHTS Page i I A. ORGAHOLEAD COHPOUHDS IS CAUCER THERAPT 6 ISTRODUCTIOH 6 EXPEEIHE5TAL 19 ; Series of Triethyl Lead Salts 19 i i Historical 19 Experimental 21 Triethyl Lead ^-Aminobenssoate 23 j Conclusion 25 Gorapoands of Lead Containing the g-Bromophenyl Gro-aps 26 Historical 26 I Experimental 27 i, 1 Triplienyl p-Bromophenyl Lead ..... 27 i Diphenyl Di ^-Bromophenyl Lead .... 28 Tetra p-Bromophenyl Lead ....... 29 Triethyl n-Bromophenyl Lead 29 S\3imiary 51 I Reformatsky Reaction 32 Introduction 32 Experimental 34 j Conclusion 37 t H^onic Ester Condensation 38 Miscellany 41 i IDiethyl Cyclopentamethylene Lead 41 I Triethyl e-'bromoamyl Lead 41 i Tidethyl e-bromoainyl Lead with Magnesium and 42 CarTjon Dioxide 42 I Diphenylaminomagnesium Brcmide with Q?rietl3yl I Lead Chloride 43 Oxidation of ITriethyl Allyl Lead ..... 44 I Diphenyl Lead Salts 45 i i t SUKBIAKY ....................... 46 - 4 - Page B. MTI-KNOGS STUDIES 47 IHTRODUCTiOF 47 EXPERIlffiSTM. 71 Methods for the Preparation of Triethyl Lead Chloride and Diethyl Lead Dichloride .... 71 Historical . 71 Trietiiyl Lead Chloride 76 Diethyl Lead Dichloride 77 Tetraethyl Lead with Chlorine 78 Siminiary 79 Mixed Alkyl Lead Compounds 80 Historical 80 Experimental 82 Triethyl n-Butyl Lead 82 Triethyl iso-Batyl Lead 83 Triethyl sec.-Batyl Lead ....... 83 Triethyl tert.-Butyl Lead 83 Conclusions 85 Alkyl-aryl Lead Compounds 86 Historical 86 E3?perimental 87 Triethyl Phenyl Lead ......... 87 Diphenyl Diethyl Lead 87 Triphenyl Ethyl Lead 88 Relative Anti-Enock Effectiveness of the Compounds 88 ConclTision 89 Series of Ethyl Methyl Lead Compounds and Tri- phenyl Lead Halides 90 Historical 90 Tetramethyl Lead 90 Trimethyl Ethyl Lead 91 Dietibyl Dimetl^yl Lead 91 Methyl Triethyl Lead 92 Triphenyl Lead Halides ........ 92 - 5 - Page Miscellany 94 Trietliyl Allyl Lead 94 Triethyl Benzyl Lead 95 Diethyl Dlallyl Lead 95 Diethyl, di tert.-Butyl Lead 95 Triethyl te^.-Amyl Lead 95 Triethyl p-Styryl Lead 99 Triethyl p-Anisyl Lead 100 Triethyl ^-Phenylethyl Lead .iqI Tetra tert.~Butyl Lead 102 Tetra Allyl Lead 103 Tetra see.~Batyl Lead 104 Dimethyl Diphenyl Lead IO5 Phenylmagnesium Bromide with. Triethyl Lead Chloride 106 Triphenyl Lead Chloride with Phenylmagnesitm Bromide I07 Aeration of Tetraethyl Lead 108 Sraae General Considerations of Manipiilations and Tests HO SUMMARY 114 A. ORaASOLSlS COMPOTJSDS IH CAHCER THSRAIT IHTRODUCnOS Coirooimds of lead offer a promising field for research.. Dttring the past fe-w years, special attention has been paid to their use as anti-kncclr reagents in internal combustion engines, as fungicides in the treatment of plant diseases and as compounds which may bs of possible use in cancer therapy. Shis urork was undertaken to study organolead compounds with reference to their possible use in these fields. Cancer is probably one of the most dreadful diseases from •shich man suffers, l^hile tuberculosis causes more deaths, the methods of treatment are fairly -Brell known. During the years between 1370 and 1830 the death rate in cancer was 40 per hun­ dred thousand in Liverpool, In 1924 the rate was 112 per hun­ dred thousand, an increase of 230 per cent. One of the largest life insiirance ccxapanies on the Pacific Coast places cancer fourth as the cause of death. In Hew Zealand, cancer is responsible for more deaths than any one other cause except organic heart disease. In 1922 it xras 85.2 per hundred thousand and in 1925 it had risen to 90.8, The reported increase in prevalence of disease, ho-wever, may be explained in two ways. In the first place, cancer is essentially an ailment of the elderly individual and so the increased life t>iat we say expect gives cancer a chance to de­ velop^ Then, as is well known, diagnosis of disease in past - 7 - years has not always "been accurate and it is highly prohahle that many persons have died of cancer larithout knowing it. But there is no douht at all of the seriousness of cancer and its prevalence. ©le sad part of the matter is that at present there are only so few instruments that may "be used in the treatment of cancer and that they result in such a high percentage of failures. Any method which will reduce this percentage will "be of tremendous assistance to the medical profession and to the public suffering from -Khiis disease. !Ehis work was under­ taken to study the preparation of organolead compounds which might he used in cancer therapy, ISetals Tffere first used in the treatment of malignant diseases hy Torres in 1904 hut there was little interest at­ tached to this type of material until the v/ork of Wassermann and Keysser (1), who in 1911 used compounds of selenium and tellurium. These coapounds were found to he effective when used to treat animal tumors, hut when used on man the effective dose was found to coincide with the lethal dose, Heuherg (2) was influenced hy Wassermann*s results to test other metals which he used in the colloidal state. Some of the metals used were lead, copper, silver, and cohalt. He had excellent suc­ cess with animals hut could not treat humans witbout poisoning (1) Wassermann and Keysser, Deutsche med. Wchnschr,, 37:2389 (1911). (2) Ueuherg, Deutsche med. Wchnschr,, 38;575(1912). i them, Caspsari (3) was tlie first to report a sli^t improve- . 1 I ment in one case of carcinoma of the tongue when treated with an aniline-silver compound, Izar (4) and Basile (5) were ahle I to cure rat sarcomas with colloidal suj.fiir "but had no success with man, ishen afflicted with this disease. j Colloidal silver was used "by Kausch (6) but he had to !f abandon its use because of severe reactions which occurred,^ • S I while BoMenburg (7) obtained no therapeutic results from a commercial preparation of colloidal silver. j 1 wfimong other copper preparations tried by Loeb {B) and f i Gaube (9) was cuprase which is colloidal copper hydrate, Al- i i though Loeb could obtain no permanent results Gaube noticed i considerable improvement in patients, but his observations were over too short a time to be of value, Bichard Weil (10) f 1 studied the problem in considerable detail and came to the j i conclusion that colloidal copper compounds did as much damage I as they did good in the treatment of malignant disease. Col- I loidal gold has been used by Carl Lewin (11) who found ttmt he I could treat transplanted mouse tumor successfully but had no 1 (3) Ueuberg, Caspari, and L6he, Berl» klin, Wchnschr., 49:1405 I (1912). I (4) Izar, Ztchr, f, ImnamitStsforsch. u, exijer, Therap,(1)15:238 I (1912), ' i (5) Izar and Basile, ibid,, 18:64(1912), I (6) lAUsch, Arch, f, klin. Chir,, 102:159(1915). ' (7) Eohdenburg, J, Hed. Besearch, ^:331(1915). (8) loeb. Interstate Med, J., 19:1015(1912).