Construction Of New Macrocyclic Compounds Possessing Propargylamine Skeleton And Study Of Their Higher-order Crystal Packing

Macrocycles are of high significance in areas as diverse as drug development and supramolecular chemistry. They can be considered as "privileged molecules" because they can combine flexibility and conformational bias. Macrocyclic structures were identified as classic objects of study existing not only in drug development, but also in areas as diverse as material sciences. In addition, macrocyclic compounds were widely applied in organic catalysis as tiny molecular reactors. Moreover, special highlights in great significance of macrocyclic compounds as the medium in host-guest chemistry, it is also an important part of supramolecular chemistry. The development of macrocycles chemistry brings inorganic chemistry and organic chemistry a special highlight. Besides, the crystal engineering is an important section of the molecular engineering, which involves the assembly behavior of molecules or chemical groups in crystal, the design of crystal and the control of the structure and function. The propargylamine backbone was introduced in macrocyclic compound which is the central theme of this work; we designed and synthesized a series of novel macrocycle with propargylamine scaffolds by introducing the propargylamine backbones into this macrocyclic compounds in this thesis. And then this special structures in the crystal were also studied based on the propargylamine derivative being a molecular assembly module which has special molecular topology.Another part of this thesis focuses on the selective synthesis of six-membered and five-membered spironaphthalenones by controlling the molar ratio of ternary Ga-In-Cu catalysts.The main contents are shown as following:In chapter1, the innovative strategies to synthesize macrocycle in recent years were reviewed. The research progress of macrocyclic compounds containing alkynyl group were focused on detailly. Then we put forward our research topics based on the idea of mentioned above.In chapter2, the design strategy to construct macrocycles architecture was applied in macrocyclic compounds via Mannich condensation reaction using the two sites of terminal alkynes and double sites of secondary amines; we successfully designed and synthesized eight novel macrocycles containing the series of [1+2+1] type and [2+4+2] type. The single-crystal structures of three [1+2+1] type products and a [2+4+2] type product were obtained.In chapter3, eight asymmetric macrocycles were synthesized successfully starting from combining a asymmetric double terminal alkyne with three asymmetric double sites of secondary amine as substrates. The single-crystal structure of [2+4+2] type product was obtained.In chapter4, we integrated Mannich condensation reaction and cross-coupling reaction of alkynes in one-pot in this part of the thesis. The polyfunctional macrocycle containing propargylamine and coupling products of alkynes to alkynes and diyne skeletons were synthesized in one-pot by three-component reaction. It is selectively controllable and highly efficient using homopiperazine as a substrate.In chapter5, bicyclization reaction played a key role in total synthesis of polycyclic compound on account of high-efficiency. We achieved the objective of bicyclization-macrocycles possessing both propargylamine and chromene skeletons from naphthalene-2,7-terminal dialkyne, piperazine and formaldehyde via three-component reaction. The synthetic strategies of a cascade bicyclization reaction with a high efficiency especially applied in total synthesis of natural products were used to construct complicated macrocycles. We used2,7-dinaphthol and two sites of secondary amine--piperazine and formaldehyde as substrates to realize the three-component reaction. Bicyclic products containing chromene skeleton and alkynyl amine skeleton were obtained successfully in one-pot.In chapter6, the unexpected triple helix was firstly discovered based on the tetrameric assembly of a macrocycle during the study of the packing the crystalline structure of the macrocycle derivatives containing propargylamine skeletons. And the senior structural form and self-assembly driving force were described detailedly.In chapter7, six-membered and five-membered spironaphthalenones were firstly synthesized selectively by controlling the molar ratio of ternary catalysts during the construction of macrocyclic basic module. The reaction conditions were optimized by adjusting the molar ratio of GaCl3/InCl3/CuCl, additives, reaction temperature and time. Six-membered spironaphthalenone was selectively obtained as the only product when the molar ratio of catalyst GaCl3:InCl3:CuCl=1.75:1:1. When the catalyst molar ratio of GaCl3/InCl3/CuCl was changed to1.5:0.75:1, the five-membered spironaphthalenon was selectively synthesized.In chapter8, the summary and prospects of this thesis were given.