72-15,188 CAMPBELL, Gerald Allan, 1946- THE CHEMISTRY OF ARYL NITRENIUM IONS. The Ohio State University, Ph.D., 1971 Chemistry, organic University Microfilms, A XERPKCompany, Ann Arbor. Michigan THIS DISSERTATION HAS BEEN MICROFILMED EXACTLY AS RECEIVED THE CHEMISTRY OF ARYL HITREPTIUM IONS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Gerald Allan Camphell, B.S. * * * * # The Ohio State University 1971 Approved by Advisor Department of Chemistry ACKNOWLEDGMENTS The author wishes to thank Dr. Paul G. Gassman for suggesting this problem and for his many ideas throughout the completion of this work. The author is also deeply grateful to his wife, Jo Ann, for her patience and encouragement during the course of this work. In addition, the author wishes to thank his parents for their help and financial support during his college education. 11 VITA Gerald Allan Campbell, son of Robert R. and Eubatinia Campbell, was born on May $0, 19^6 in Cincinnati, Ohio. He obtained his primary and secondary education in Deer Park, Ohio. In September, 1964 he entered The University of Cincinnati where he received his B.S. in Chemistry in August, 1 9 67. In September, 196% he entered the Graduate School of The Ohio State University. He married Jo Ann Broxterman of Deer Park, Ohio in December, 1967. While at The Ohio State University, he held the positions of a National Defense Education Act Fellow and a Stauffer Fellow. In December, 1971 he received his Ph.D. in organic chemistry from The Ohio State University. Ill TABLE OF COIITEOTS Page ACKNOWLEDGafflJTS ......................................... 11 VITA .................................................. ill TABLES ................................................ vlil ILLUSTEATIONS .......................................... ix INTRODUCTION ........................................... 1 PART I. Historical ................................. 1 PART II. The Problem ............................... 20 RESULTS AND DISCUSSION ................................... 51 PART I. Synthesis and Solvolysls of N-Chloro-N- alkylanlllnes .............................. 51 PART II. Synthesis and Solvolysls of N-Alkyl-N- arylhydroxylamine p-Nitrobenzoates ............ 58 PART III. Nucleophilic Aromatic Substitution of Indole Derivatives .............................. ÔJ EXPERIMENTAL ........................................... 87 N-t-Butylanlllne 87 N-t-Butyl-p-tolul dine 87 N-t-Butyl-p-anls idine (Ipla) ......................... 88 N-t-Butyl-o-anisi dine (102a) ......................... 88 N -t-Butyl -o-t oluldine ............................... 89 N-t-Butyl-p-fluoroanillne ............ 89 IV Page U_t-Butyl-£-chloroaniline (l04a) ...................... 89 N -t-Batylamino ) b ipheny 1 ........................... 90 Ethyl p-(N-t-Butylamino)benzoate ...................... 90 p-(N-t-Butylamino)nitrobenzene ........................ 91 p-(N-t-Butylamino)benzonitrile (9%) .................... 91 Chlorination and Solvolysis of N-t-Butylaniline (9^ ..... 92 Chlorination and Solvolysis of N-t-Butyl-p-tolni dine ( 9 8 ) .. 95 4-methyl-4 -methoxy-2,5 -cyclohexadienone N-t-Butyl- imine ( 10^ ) ........................................ 94 Chlorination and Solvolysis of N-t-Butyl-p-fluor o- aniline ........................... 7 .............. 95 Chlorination and Solvolysis of N-t-Butyl-p-chloro- aniline ( 104a) ........... 96 Chlorination and Solvolysis of p-( N-t-Butylamino) biphenyl .. 97 Chlorination and Solvolysis of Ethyl p^-( N-t-Butylamino) - benzoate ............................7.............. 98 Chlorination and Solvolysis of p-( N-t-Butylamino) nitro­ benzene ............................................. 100 Chlorination and Solvolysis of p-( N-t-Butylamino)- benzonitrile ( 9%) .................................. 101 Chlorination and Solvolysis of N-t-Butyl-o-toluidine ...... 102 Chlorination and Solvolysis of N-Methylaniline ........... 105 2,6,N-Trimethylaniline ............................... 104 Chlorination and Solvolysis of 2,6,N-Trimethylaniline ..... 104 Chlorination and Solvolysis of o-( N-Methylamino) - biphenyl ........................................... I06 N-t-Butyl-N-phenylhydroxylamine p-Nitrobenzoate (l42) lOT Page Solvolysis of H-t-Butyl-H-phenylhydroxylamine £-Nitro- benzoate ( .7............................. 108 N-t-Butyl-N-(£-tolyl)hydroxylamine .................... IO9 N-t-Butyl-N-(p-tolyl) hydroxy lamine p_-Nitrobenzoate ( 151) ••• 110 Solvolysis of N-t-Butyl-N-(p-tolyl)hydroxylamine p-nitrobenzoate fl^l) ................................ Ill Transestérification of o-( N-t-Butylamino) phenol p-Nitrobenzoate ( l ^ ................................ 112 3 -Chloro-2,3 -d-imethylindolenine ( 168) .................. 112 5-Methoxy-2,5-âimethylindolenine ( l6^ ) ................. II5 2 -Carboethoxy-3 -methoxy-3 -methylindolenine .............. 113 2-Oxobutyric Acid PhenyIhydrazone (17^) ................ Il4 2 -Carboethoxy-3 -methylindole ( lj6) .................... 115 2 -%rdroxymethyl-3 -methylindole (]J%) ................... 115 2 -%rdroxymethyl-3 -methyl Indole Acetate ( 174) ............ 115 Chlorination and Acetolysis of 2,3 -Dimethylindole ........ II6 Nydride Reaction of 2-Hydroxymethyl-3-methylindole Acetate (ijCit) ...................................... II6 2-Methoxymethyl-3-methylindole ( IT^) ................... 117 Chlorination and Methanolysis of 2,3 -Dimethylindole ...... II8 N-%rdroxy-2 -phenylindole ( 178] ........................ II8 N-Hydroxy-2-phenylindole p-Nitrobenzoate ( IJ^) .......... II8 2-Phenyl-3-indolol p-Nitrobenzoate (180) ............... II9 2-Nitrobenzylidinemalonate ( l82) ...................... 120 Diethyl o-Cyano-Q'-nitrobenzylmalonate ( 183^ ............. 120 N-%rdroxy-3 -cyanoindole-2-carboxylic Acid .............. 120 VI Page ïï-Iîydroxy-2 -carlDoethoxy-5 -cyanoindole ( l84) ............. 120 N-Hydroxyoxindole ( l88 ) .............................. 120 N-îîydroxyoxindole g-Nitrobenzoate ( 189) ................ 120 Transestérification of N-Hydroxyoxindole p-Nitro- benzoate (l8p) ..................................... 121 Methanolysis of N-Hydroxyoxlndole p-Toluenesvilfonate ..... 121 Methanolysis of N-H&rdroxy ox indole p-Nitrobenzene- sulfonate .......................................... 122 hydrolysis of N-I^rdroxyoxindole p^-Toluenesulfonate ....... 123 Methanolysis of N-hydroxy-2-carboethoxy-3-cyanoindole £-Toluene sulfonate .................................. 123 KINETICS ............................................... 124 Reagents .......................................... 124 Procedure .......................................... 125 Product Studies .................................... 125 Product Yields ..................................... 125 REFERENCES ............................................. 126 VI1 TABLES Table Page 1. Migration Aptitudes in Ketone Oxime Rearrangements ....... 6 2. Rates and Products of N-Chloroaziridine Solvolysis ....... 13 3* N-Chloro-N-alkylanilines ............................. 55 4. Percentage of Methoxy Products from the Silver Ion- Assisted Methanolysis of K-Chloro-N-t-butylanilines ...... 46 5. Rates of Rearrangement of R-Chloroanilines in Ethanol Buffered with 0.1 R Acetic Acid - 0.1 R Sodium Acetate ... 49 6. Products from the Solvolysis of pa£a-Substituted R-Chloro-R-t-butylanilines in Buffered Ethanol .......... 52 7 . Products from the Solvolysis of para-Substituted R - Chlor o -R -t-butylaniline s in Pure Ethanol ............. 55 Vlll IIIiUSTRATIOITS Figure Page •4* 1. a 2 Plot for the Solvolysis of U-Chloro-W-t-butylanilines in Buffered Ethanol.. ................................. 51 2. Kinetic Behavior of Ethyl p-(N-Chloro-N-t-butylamino)- benzoate in Buffered and Unbuffered Ethanol ............. 56 XX IliffiRODUCTION Part I. Historical The chemistry of carhonium ions has received a vast amount of attention from organic chemists during the past $0 years. In view of the extensive information available on the trivalent, electron- deficient carbon species (l), it is rather surprising that until the 1 recent work of Gassman and co-workers very little was known about the (l) P. G. Gassman, Accounts Chem. Res., ^ 26 (l9T0), nitrenium ion, the nitrogen analogue of the carbonium ion. This divalent, electron-deficient nitrogen species (2_) has six electrons in its valence shell and is isoelectronic with the carbonium ion. On El El 1+ u Eg— C ;N I I E g E g 1 2 comparing the relative reactivities of 1 and 2_, the electronegativities of carbon and nitrogen indicate that of the two isoelectronic species, the nitrenium ion should be the more reactive. However, an important factor which requires consideration is that the nitrenium ion differs 2 from most positive ions of interest to the organic chemist in that it possesses a nonhonding pair of electrons. This unique characteristic enables the nitrenium ion to exist in either a singlet spin state or a 2 triplet spin state. Sclvolytically generated nitrenium ions would (2 ) P. G. Gassman and R. L. Cryberg, J. Amer. Chem. Soc., 91, 517^ (1969). initially be, of necessity, in the singlet state with the electron spins paired (J^). The singlet species could, however, undergo a spin inversion to yield the triplet nitrenium ion (5 ). The singlet would Cl I + R — N-R --- > R-R-R ^ R-R-R-K- ê 6 thus be expected to exhibit carbonium ion-like behavior while the triplet would be expected to resemble a nitrogen cation radical in its chemical reactivity. The first example of nitrenium ion chemistry