The design of partially reduced 1,1'-bisisoquinoline derivatives was investigated with the aim of controlling the conformation about the C1-C1' axis. This would produce ligands with unusual but predictable ligand binding properties, particularly cooperativity. The introduction of ??-aminoalkyl, ??-azidoalkyl, ??-alkynyl and ??-alkenyl groups onto the nitrogens of the reduced bisisoquinoline core was conducted with the intention of broadening the scope of the ligand. Subsequent epoxidation, hydroboration and Huisgen 1,3-dipolar cycloaddition of terminal unsaturated groups and nucleophilic displacement of the chlorine of the corresponding known bischloroacetyl derivative afforded representative examples of new ligand types for future study. 1,1'-Bis(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline) was found to readily condense with a wide range of aldehydes to give imidazolines and aspects of the rates of condensation were determined. Mono-alkyl bisisoquinolines were obtained efficiently by cleavage of the imidazolines through a newly defined treatment with sodium cyanoborohydride under acidic conditions. A procedure was developed whereby these two steps could be accomplished in a sequential one-pot process. The mono-alkyl compounds were further derivatized through acetylation, alkylation, sulfonylation and reductive alkylation. Synthetic strategies towards ??-excessive N-arenealkyl derivatives were established with the goal to create scaffolds for the coordination of ??-deficient systems, of which the X-ray crystal structures of three N-arenemethyl derivatives were elucidated. These are each closely related in conformation about the C1-C1' axis. Reaction of two examples of the N-arenealkyl compounds with copper(II) and palladium(II) chlorides, furnished the first known examples of this type of highly reduced 1,1'-bisisoquinoline-metal complex. Single crystal X-ray crystallography was used to analyse the structures of these complexes in the solid state. Preliminary physicochemical investigations were conducted with a view to determining the conformation of the molecules about the bisisoquinoline C1-C1' bond. The interaction of intermolecular N-aryl ??-excessive compounds with ??-deficient systems was found to result in minimal spectroscopic changes. Complementary intramolecular ??-excessive/??-deficient systems were found through fluorometric analysis to readily form charge transfer complexes. Finally, it was determined that the conformation of 1,1'-bis[2-(methoxy-18- crown-6)ethanoyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline] could be controlled by the simultaneous coordination of the termini of the diperchlorate salt of 1,3-diaminopropane to the crown ether moieties of the ligand. A range of new N-substituted bisisoquinolines have been synthesised and methods developed for determining interactions between parts of these molecules that through these physicochemical characteristics could allow monitoring of conformational behaviour in future studies. Keywords: 1,1'-bisisoquinoline, conformational analysis, supramolecular chemistry, functional ligands, metal complexes.

The design of partially reduced 1,1'-bisisoquinoline derivatives was investigated with the aim of controlling the conformation about the C1-C1' axis. This would produce ligands with unusual but predictable ligand binding properties, particularly cooperativity. The introduction of ??-aminoalkyl, ??-azidoalkyl, ??-alkynyl and ??-alkenyl groups onto the nitrogens of the reduced bisisoquinoline core was conducted with the intention of broadening the scope of the ligand. Subsequent epoxidation, hydroboration and Huisgen 1,3-dipolar cycloaddition of terminal unsaturated groups and nucleophilic displacement of the chlorine of the corresponding known bischloroacetyl derivative afforded representative examples of new ligand types for future study. 1,1'-Bis(1,2,3,4-tetrahydro-6,7-dimethoxyisoquinoline) was found to readily condense with a wide range of aldehydes to give imidazolines and aspects of the rates of condensation were determined. Mono-alkyl bisisoquinolines were obtained efficiently by cleavage of the imidazolines through a newly defined treatment with sodium cyanoborohydride under acidic conditions. A procedure was developed whereby these two steps could be accomplished in a sequential one-pot process. The mono-alkyl compounds were further derivatized through acetylation, alkylation, sulfonylation and reductive alkylation. Synthetic strategies towards ??-excessive N-arenealkyl derivatives were established with the goal to create scaffolds for the coordination of ??-deficient systems, of which the X-ray crystal structures of three N-arenemethyl derivatives were elucidated. These are each closely related in conformation about the C1-C1' axis. Reaction of two examples of the N-arenealkyl compounds with copper(II) and palladium(II) chlorides, furnished the first known examples of this type of highly reduced 1,1'-bisisoquinoline-metal complex. Single crystal X-ray crystallography was used to analyse the structures of these complexes in the solid state. Preliminary physicochemical investigations were conducted with a view to determining the conformation of the molecules about the bisisoquinoline C1-C1' bond. The interaction of intermolecular N-aryl ??-excessive compounds with ??-deficient systems was found to result in minimal spectroscopic changes. Complementary intramolecular ??-excessive/??-deficient systems were found through fluorometric analysis to readily form charge transfer complexes. Finally, it was determined that the conformation of 1,1'-bis[2-(methoxy-18- crown-6)ethanoyl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline] could be controlled by the simultaneous coordination of the termini of the diperchlorate salt of 1,3-diaminopropane to the crown ether moieties of the ligand. A range of new N-substituted bisisoquinolines have been synthesised and methods developed for determining interactions between parts of these molecules that through these physicochemical characteristics could allow monitoring of conformational behaviour in future studies. Keywords: 1,1'-bisisoquinoline, conformational analysis, supramolecular chemistry, functional ligands, metal complexes.

Thesis (M.S.)--Virginia Polytechnic Institute and State University, 1991. / Vita. Abstract. Includes bibliographical references (leaves 114-119). Also available via the Internet.

Thesis (doctoral)--Universität Jena, 1912.

This thesis has two parts. The first deals with the conformational behaviour of Nsubstituted and N-unsubstituted bis-tetrahydroisoquinoline derivatives under neutral and acidic conditions and the second describes the design, synthesis and structural characterization of a new class of N-ureidyl bis-tetrahydroisoquinoline derivatives, potential catch and release agents. Four N-alkyl derivatives, two of which were new, were studied in detail for their conformational behaviour and their spectroscopic properties compared extensively with N-unsubstituted compounds. NMR chemical shift changes and vicinal spin couplings were measured and related to conformational change within the heterocyclic rings and about the central C1-C1' axis. The basicity of the amines were determined through pKa measurements, and differences between the behaviour of secondary and tertiary amine examples discussed. Analysis of titration results revealed the formation of discrete 1:1 and 1:2 complexes between the secondary examples and added carboxylic acids, but only 1:1 complexes in the case of tertiary amine complexes. Monitoring of changes in conformation with incremental addition of acid provided new understanding about modes of binding. A new class of nine ureidyl bis-tetrahydroisoquinoline derivatives has been prepared. These contain N'-aryl and N'-adamantyl urea groups attached to the bisisoquinoline core through alkyl linker groups with varying length. The conformation of these derivatives were heavily dependent upon the linker length while the nature of the urea group (in one case a thiourea) played a small role in the preferred conformation of the bis-tetrahydroisoquinoline. Three non-isoquinoline derived model ureidyl amine systems were also synthesized for comparative studies. Four partner ureidyl acids were prepared and their pKa values in DMSO were measured. Studies of the interaction of the ureidyl acids with the ureidyl amines revealed that the chain length of the ureidyl bistetrahydroisoquinoline linker played a small role while the remote aryl and adamantyl groups of both acids and amines played a more important role. DMSO was found to interfere with the normal conformations of the ureidyl bis-tetrahydroisoquinolines and with the interaction of the ureidyl bis-tetrahydroisoquinolines with their partner ureidyl acids in deuterochloroform. The latter studies will provide the basis for future design of catch-and-release agents derived from bis-tetrahydroisoquinolines.

Typescript (photocopy) / v, 169 leaves : ill. ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.) Dept. of Organic Chemistry, University of Adelaide, 1982

A new approach to isoquinoline skeleton, we use this way to make many isoquinoline skeleton compound, and we hope this method could apply on natural products and photoelectric materials in the future.

This thesis has two parts. The first deals with the conformational behaviour of Nsubstituted and N-unsubstituted bis-tetrahydroisoquinoline derivatives under neutral and acidic conditions and the second describes the design, synthesis and structural characterization of a new class of N-ureidyl bis-tetrahydroisoquinoline derivatives, potential catch and release agents. Four N-alkyl derivatives, two of which were new, were studied in detail for their conformational behaviour and their spectroscopic properties compared extensively with N-unsubstituted compounds. NMR chemical shift changes and vicinal spin couplings were measured and related to conformational change within the heterocyclic rings and about the central C1-C1' axis. The basicity of the amines were determined through pKa measurements, and differences between the behaviour of secondary and tertiary amine examples discussed. Analysis of titration results revealed the formation of discrete 1:1 and 1:2 complexes between the secondary examples and added carboxylic acids, but only 1:1 complexes in the case of tertiary amine complexes. Monitoring of changes in conformation with incremental addition of acid provided new understanding about modes of binding. A new class of nine ureidyl bis-tetrahydroisoquinoline derivatives has been prepared. These contain N'-aryl and N'-adamantyl urea groups attached to the bisisoquinoline core through alkyl linker groups with varying length. The conformation of these derivatives were heavily dependent upon the linker length while the nature of the urea group (in one case a thiourea) played a small role in the preferred conformation of the bis-tetrahydroisoquinoline. Three non-isoquinoline derived model ureidyl amine systems were also synthesized for comparative studies. Four partner ureidyl acids were prepared and their pKa values in DMSO were measured. Studies of the interaction of the ureidyl acids with the ureidyl amines revealed that the chain length of the ureidyl bistetrahydroisoquinoline linker played a small role while the remote aryl and adamantyl groups of both acids and amines played a more important role. DMSO was found to interfere with the normal conformations of the ureidyl bis-tetrahydroisoquinolines and with the interaction of the ureidyl bis-tetrahydroisoquinolines with their partner ureidyl acids in deuterochloroform. The latter studies will provide the basis for future design of catch-and-release agents derived from bis-tetrahydroisoquinolines.

Thesis (Ph.D. 1978) from the Department of Organic Chemistry, University of Adelaide.

Thesis (Ph.D.) Dept. of Organic Chemistry, University of Adelaide, 1982. / Typescript (photocopy).