Iowa State University Capstones, Theses and Retrospective Theses and Dissertations Dissertations 1957 Organometallic derivatives of quinoline and isoquinoline Theodore Stephen Soddy Iowa State College Follow this and additional works at: https://lib.dr.iastate.edu/rtd Part of the Organic Chemistry Commons Recommended Citation Soddy, Theodore Stephen, "Organometallic derivatives of quinoline and isoquinoline " (1957). Retrospective Theses and Dissertations. 1354. https://lib.dr.iastate.edu/rtd/1354 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]. ORG-ANOMETALLIC DERIVATIVES OF QUINOLINE AND ISOQUINOLINE Theodore Stephen Soddy A Dissertation Submitted to the Graduate Faculty in Partial Fulfillment of The Requirements for the Degree of DOCTOR OF PHILOSOPHY Major Subject: Organic Chemistry Approved: Signature was redacted for privacy. In Charme of Major Work Signature was redacted for privacy. ead of Major Department Signature was redacted for privacy. Dean of Graduate College Iowa State College 1957 il TABLE OF CONTENTS Page INTRODUCTION 1 HISTORICAL 3 Introduction 3 The Addition of Grignard Reagents to Pyridine, Quinoline, and Isoquinoline 4 The Addition of Organolithium Reagents to Pyridine, Qulnollne, Isoquinoline and Some of Their Derivatives 6 Grignard Reagents of Pyridine and Quinoline 10 Organolithium Reagents of Pyridine, Quinoline, and Isoquinoline 15 By the halogen-metal interconversion reaction 15 By the metalation reaction 17 Other Organometalllc Derivatives of Qulnoline and Isoquinoline 19 Mercury 19 Tin 20 Organometaloid Derivatives of Quinoline 20 Arsenic 20 Antimony 22 Phosphorus 22 Tellurium 22 The Preparation of Organometalllc Compounds in Tetrahydrofuran 23 Grignard reagents 23 Organolithium reagents 25 Metalations in Tetrahydrofuran 26 EXPERIMENTAL 29 Introduction 29 Derivatives 29 Ill Page n-Butyllithium 29 1-(4-Blphenylyl)ieoqulnoline 31 1-(2-Biphenylyl)isoquinoline. Run I 31 Run II 32 Run III. Inverse addition 32 jd-B1b-( 2-qulnolyl)benzene 33 £-Ble-(l-ieoqulnolyl)benzene (attempted). Run I 34 Run II 34 4,4*-Bis-(2-quinolyl)biphenyl 35 4,4l-Bie-(l-ieoquinolyl)biphenyl (attempted). Run I 36 Run II 2-(]>-Terphenyl-4-yl)quinoline 37 l-(j2-Terphenyl-4-yl)isoquinoline (attempted). Run I 37 Run II 38 l-(o<-Naphthyl)ieoqulnoline (attempted) 38 1-( "^-Naphthyl)isoquinoline (attempted) 39 2-Propenyl-l,2-dihydroqulnollne 39 2-Propenylquinoline 40 2-Propylquinoline 4l The catalytic hydrogénation of 2-propenyl- qulnollne 4l Propenylmagnesium bromide in tetrahydrofuran 42 2-Propenylquinoline from propenylmagnesium bromide and quinoline (attempted) 42 Propenylllthium 43 2-Propenyl-l,2-dlhydroquinoline from propenylllthium and quinoline 44 2-Propenylquinoline 44 The reaction of allylmagnesium bromide with lepldlne In ether 45 7-Chloro-4-qulnolylmagneslum chloride (attempted) 45 The preparation of activated magnesium 46 The attempted preparation of 7-chloro-4- quinolylmagneslum bromide by use of activated magnesium 46 3-Qulnolylmagneslum bromide in tetrahydrofuran (attempted; 47 6-Q,uinolylmagnesium bromide (attempted) 47 4-Bronoqulnoline 48 4-Quinolylllthlum 48 »<,e< -Diphenyl-4-quinollnemethanol 49 4-Quinolinecarboxylic acid 49 iv Page 2-( jd-Br omophenyl )quinol ine 50 2-(2-Garboxyphenyl)quinollne 51 2-[£-( Trime thylsilyl )phenyl] quinoline 52 Method I 52 Method II 53 m-Bromophenyllithium 5& 2-(m-Bromophenyl)quinoline 5^ 2-(m-Carboxyphenyl)qui noline 55& 2-Picolinic acid 55& ô-Bromo-2-picolinic acid 55b 2-Pyr idylp he none 55b oc, o( -Diphenyl-2-pyridinemethanol 56 Method I 56 Method II 57 4,4'-Dipyridylketone (attempted) 57 2-Quinolineboronic acid ( attempted) 58 3-Quinolineboronic acid (attempted) 58 2-Pyridineboronic acid (attempted) 59 2-(m-Boronophenyl)quinoline 59 2-(2-Bor0nophenyl)quinollne (attempted) 60 Trlphenyl-2-quinolylsilane (attempted) 60 Trlmethyl-2-quinolyls ilane (attempted) 61 2-Me s1tyllithium 62 The metalation of 2-phenylquinoline (attempted) 62 2-( 2f- Trip he nyl s ilylpropy 1 )quinol ine (attempted) 62 The reaction of allylmagnesium bromide with triphenylsilane (attempted) 63 4-Chloro-2-quinolineacetic acid (attempted) 63 £-Hthlo-i>'-hydroxyazobenzene (attempted) 64 Bromination of quinoline (attempted) 64 3-Q,uinolylmagnesium bromide in ether 65 3-Allylquinoline (attempted) 66 The reaction of 4-bromoisoquinoline with magnesium in ether (attempted) 66 DISCUSSION 67 The Addition of Organolithium Reagents to Quinoline and Isoquinoline 67 The Addition of Aryllithium Reagents to 1-Arylisoquinoline Derivatives 70 The Addition of Grignard Reagents to Quinoline 70 V Page The Preparation of Organolithium Reagents of Pyridine, Quinoline and Isoquinoline 72 The Preparation of Organomagneslum Derivatives of Quinoline 77 Liquid Solution Scintillators 78 Boronic Acid Derivatives of Quinoline 82 Miscellaneous Reactions 84 Suggestions for Further Research 86 SUMMARY 88 ACKNOWLEDGMENTS 90 1 INTRODUCTION In the field of organic synthetic chemistry the organo­ lithium and organomagneslum reagents enjoy a wider degree of applicability than any other group of organometalllc compounds. The organolithium and organomagneslum compounds are prepared and handled with relative ease in the laboratory. Another Im­ portant criterion of their usefulness is that they complement each other in the sense that where a certain organomagneslum compound cannot be prepared, the corresponding organolithium compound can be made in good yield. Of the very highly reactive types of organolithium com­ pounds which are capable of the halogen-metal Interconversion reaction, n-butylllthlum has been used most extensively in this reaction^. By use of the halogen-metal Interconversion reaction here­ tofore inaccessible organolithium compounds of quinoline and isoquinoline were obtained in good yields, such as 2- and 4-qulnolyl- and 1- and 4-isoquinolylllthium. Part of this work was an attempt to prepare some new 1-substituted isoqulnolines and 2-substltuted quinolines by the addition of some alkyl- and aryllithlum reagents to the anil linkage of isoquinoline and quinoline, respectively. "4l. G. Jones and H. Gilman In Adams "Organic Reactions Vol. jé>, New York, J. Wiley & Sons, Inc. 1951• 2 A second part of this Investigation was undertaken to pre­ pare some quinoline and isoquinoline derivatives which could be used as organic liquid scintillator solutes and to correlate the scintillator activity with the activity of closely related aza-aromatic he terocycles. The scintillator activity of these compounds was evaluated by Drs. Wright H. Langham, F. Newton Hayes and Donald G-. Ott of the Los Alamos Laboratories. A third phase of this work was to synthesize some quinollne- boronlc acid derivatives for possible use in brain tumor therapy. 3 HISTORICAL Introduction The historical section is devoted to a review of the chemical literature which concerned the organometalllc deriva­ tives of quinoline for the past twenty-five years and the organometaloid derivatives of quinoline for the past fifty years. For a more thorough discussion of the earlier work and other studies related to this subject, the following literature citations should be consulted . The numbering system for pyridine(I), quinoline (II), and isoquinoline (III) is that which is employed by Chemical Abstracts. M. Spatz, Unpublished Ph.D. Thesis. Ames, Iowa, Iowa State College Library (l?4l). 3 &. C. Gainer, Unpublished Ph.D. Thesis. Ames, Iowa, Iowa State College Library (1946). ^"J. A. Beel, Unpublished Ph.D. Thesis. Ames, Iowa, Iowa State College Library (1949). "*W. A. Gregory, Unpublished M.S. Thesis. Ames, Iowa, Iowa State College Library (1942). ®M. S. Kharasch and 0. Relnmuth, "Grignard Reactions of Nonmetallic SubstancesNew York, Prentice-Hall, Inc. (1954). 4 6 fe Z T Z 1 XN' i n in The Addition of Grignard Reagents to Pyridine, Quinoline, and Isoquinoline The first reported addition of a Grignard reagent to an aza-aromatic heterocycle was the result of an investigation by Oddo?. A small yield of 2-phenylquinoline was obtained when a mixture of magnesium, quinoline, bromobenzene, and toluene was heated on an oil bath at l40°, or when a mixture of phenyl- magnesium bromide, quinoline, and pyridine was refluxed for two p hours. In a later investigation Bergstrom and McAllister ob­ tained 2-phenylqulnollne in a yield of QQ% by autoclavlng an ethereal solution of quinoline and phenylmagneslum bromide at 150-160° for three hours. 7B. Oddo, Attl accad. naz. Lineel Rend.. [4], 16, Part I, 413, 538 (1907). Q F. W. Bergstrom and S. H. McAllister, J. Am. Chem. Boo.. 12, 2845 (1930). 5 Bergmann and Rosenthal^ added benzylmagneslum chloride to pyridine and isolated a compound which they thought to be 2-benzylpyridine. Later work by Veer and Goldschmidt"^ demon­ strated that the 2-Isomer was not the product from this reac­ tion, but 4-benzylpyridlne was obtained. Bergmann and Rosenthal had been misled by the fact that both the 2- and 4-isomers formed picrates which melted at the same temperature. Veer and Goldschmidt employed Adams catalyst in dilute hydro­ chloric acid to reduce the 4-benzylpyridine and 2-benzylpyri­ dine to the corresponding piperidine derivatives. 2-Benzyl- pyridine gave rise solely to 2-benzylpiperidlne, but the 4-isomer gave both 4-benzylpiperidlne