This thesis explores the reaction of primary amines with 1,2-dibromoethane and 1,3-dibromopropane as a one step synthesis of N,N"-disubstituted ethylenediamines, RNH- CH2CH2-NH-R, N,N"-disubstituted propanediamines, R-NH-CH2CH2CH2-NH-R and N-substituted azetidines RN[(CH2)3]. Unlike earlier approaches in the literature, this method circumvents the use of the highly toxic #-haloamines. The reaction can also be a convenient approach to N,N",N""-trisubstituted diethylenetriamines which form as byproducts in the synthesis of the ethylenediamines and are readily separated by distillation. The respective propylenetriamines were obtained in analogous fashion from 1,3-dibromopropane. The use of N,Nʼ,N”- trisubstituted triamines for the stabilization of low valent main group compounds was exemplified through the synthesis and structural characterization of a phosphenium salt. N,N'-disubstituted ethylenediamines, R-NH-CH2CH2-NH-R" bearing different substituents R are difficult to obtain and require multi-step protocols. This thesis describes their one step synthesis from aziridines and primary amines. The analogous 1,3-propandiamines were obtained from primary amines and azetidines. N-tert-Butylimidazol was obtained through thermolysis of 1,3-di-tertbutylimidazolium chloride and used as precursor for bis carbenes.

Antergan is one of the ethylenediamine type of antihistamines; in this work ten analogues of it were prepared. That pπ conjugation is essential to antergan's antihistaminic activity has already been established. Six of these analogues (A-l a-d, and B-l and 2, illustrated in Fig. 2 , p. 4 ) were synthesized in order that the significance of pπ conjugation in the antihistaminic properties of antergan molecule may at some future time be investigated. The problem is to find in what way alteration (i. e. , increase or decrease in) electronic density of the pπ -conjugated moiety of the molecule affects antihistaminic activity. The analogues A-l a-d involved ortho-, meta-, and para-methyl, and para-bromo substitution to the aromatic ring which gives rise to pπ conjugation in the antergan molecule; while the ring which gives rise to homo conjugation was replaced by a cyclohexyl moiety to eliminate any possible contribution of homoconjugation to antihistaminic activity. In analogue B-l, the antergan structure was modified so that the aromatic ring which gives rise to pπ, conjugation was removed from the rest of the molecule by a methylene group, i.e. , the phenyl group was replaced by a benzyl moiety. The other ring was left unmodified. Another compound (B-2) relocated the aromatic ring giving rise to pπ conjugation to the adjacent methylene carbon, so that pπ conjugation was eliminated; this compound is the nitrogen analogue of diphenhydramine and thiodiphenhydramine. In order that the importance of homo conjugation to antergan's antihistaminic activity may be established, the aromatic ring which gives rise to pπ, conjugation was replaced by a cyclohexyl moiety (A-3). Two compounds were synthesized in which the aromatic ring giving rise to homoconjugation were replaced by 3-cyclohexyl moieties (A-2a and b); while the aromatic ring which gives rise to pπ, conjugation was left unaltered in one of the compounds (b) and replaced by a cyclohexyl moeity in the other (a). In the tenth compound (A-1 e), both aromatic rings giving rise to both homo- and pπ - conjugation were removed and replaced by cyclohexyl moieties. The resulting analogue of antergan has already been demonstrated to have a very low antihistaminic activity compared to diphenhydramine, but it was felt that it would provide a useful comparison for the antihistaminic activities of the other antergan analogues prepared in this work. Two final intermediates in the synthesis of other analogues of antergan were prepared. In these analogues (C-2a and b) the aromatic ring giving rise to homoconjugation would have been replaced by the 1-cyclohexenyl moiety, while the other aromatic ring which gives rise to pπ conjugation would have been the same in one of the analogues, and replaced by a cyclohexyl moiety in the other. In intermediates of analogues D-l and 2, the ring giving rise to homoconjugation would have been replaced by 2, 5- and 1,4-cyclohexadiene respectively, while the aromatic ring giving rise to Pπ conjugation was replaced by the cyclohexyl moiety. In intermediates D-3 and 4, the aromatic ring giving rise to homoconjugation would have been replaced by cyclohexyl, while the aromatic ring giving rise to pπ, conjugation would have been replaced by 2, 6-dimethylphenyl and 3-cyclohexenyl moieties. / Pharmaceutical Sciences, Faculty of / Graduate