A novel approach for functionalising and separating Tröger's Base Analogues
(2023) KASM05 20231Centre for Analysis and Synthesis
- Abstract
- Tröger’s Base (TB) is a bicyclic compound containing a methanodiazocine group between two aromatic rings. The methylene bridge forces the molecule to have a bent formation; thus, the aromatic rings are close to 90 degrees relative to each other, resulting in a rigid concave aromatic cavity. These unique properties make TB a great candidate as a molecular cleft compound and a good structure as a molecular receptor towards unfunctionalised molecules. The Tröger’s Base framework has therefore been found to be a useful building block in supramolecular chemistry. The Tröger’s Base project aims to complete a total synthesis of a linearly fused heptakis Tröger’s Base analogue. As a part of this project, the goals of this master thesis are to... (More)
- Tröger’s Base (TB) is a bicyclic compound containing a methanodiazocine group between two aromatic rings. The methylene bridge forces the molecule to have a bent formation; thus, the aromatic rings are close to 90 degrees relative to each other, resulting in a rigid concave aromatic cavity. These unique properties make TB a great candidate as a molecular cleft compound and a good structure as a molecular receptor towards unfunctionalised molecules. The Tröger’s Base framework has therefore been found to be a useful building block in supramolecular chemistry. The Tröger’s Base project aims to complete a total synthesis of a linearly fused heptakis Tröger’s Base analogue. As a part of this project, the goals of this master thesis are to acylate the benzylic position of a TB analogue and to separate the resulting diastereomers with dry column vacuum chromatography. In order to achieve these two goals, six synthesis steps have been performed, starting from a commercially available aniline analogue. The aniline analogue was halogenated, followed by a condensation reaction to form the first TB analogue. After four more synthesis steps, including dehalogenation, Pd-catalyzed amination, amine protection, and acylation, where the benzylic position of a TB analogue finally functionalised. Afterwards, one of the diastereomers was successfully separated from the mix of diastereomers with a dry vacuum column using silica. As a result, this thesis work has shown it possible to acylate a TB analogue at the benzylic position and shown that the resulting mix of diastereomers is separable by dry column vacuum chromatography. In addition, the work has given valuable TB analogues, which can be used in further synthesis in the Tröger’s Base project. (Less)
- Popular Abstract
- Supramolecular chemistry focuses on the forces between molecules and how molecules interact to form complex systems of molecules. Supramolecular systems can be designed for specific purposes, such as transporting specific molecules or speeding up a particular chemical reaction. One molecule that has shown exciting properties within this field is Tröger’s Base (TB). This molecule has a V-shaped structure, resulting in a cavity in which hydrophobic molecules can interact. TB also possesses a rigid structure and therefore does not tend to alter its shape, making this molecule an excellent building block for making supramolecular systems.
In this project, called the Tröger’s Base project, the goal is to synthesize a large analogue of TB... (More) - Supramolecular chemistry focuses on the forces between molecules and how molecules interact to form complex systems of molecules. Supramolecular systems can be designed for specific purposes, such as transporting specific molecules or speeding up a particular chemical reaction. One molecule that has shown exciting properties within this field is Tröger’s Base (TB). This molecule has a V-shaped structure, resulting in a cavity in which hydrophobic molecules can interact. TB also possesses a rigid structure and therefore does not tend to alter its shape, making this molecule an excellent building block for making supramolecular systems.
In this project, called the Tröger’s Base project, the goal is to synthesize a large analogue of TB consisting of seven TB bridges, a heptakis Tröger’s Base analogue. This molecule is envisioned to function as a host molecule, in other words, to bind to smaller molecules reversibly. This could be useful in medicinal applications, like drug delivery. By synthesizing this molecule, the supramolecular properties and the potential applications of the molecule could be discovered.
As a part of this project, the focus of this work has been to form a TB analogue needed as a building block for the heptakis TB analogue. The procedure for obtaining this TB analogue can be described as doing multiple reactions; starting with a simple molecule on which new pieces are added under specific conditions until the final structure is formed. In addition, much work has been done to separate the diastereomers of this TB analogue which are formed in the final reaction step. Diastereomers of a compound can be described as molecules that differ in molecular configuration; in other words, having different arrangement of atoms but are made of the same set of atoms. In many cases, it is desirable to have the diastereomers separated, this because they have different chemical and physiological properties. Therefore, a method called chromatography has been used to investigate if these diastereomers can be separated. Chromatography is a separation method in which a column is packed with a stationary (solid) phase together with the product and rinsed with a mobile (liquid) phase. Due to diastereomers having differences in the affinity to the stationary and the mobile phase, the diastereomers will elute from the column at different times and can therefore be collected separately.
As a result, six synthesis steps have been completed, and one of the two diastereomers has been separated from the mix of diastereomers. The outcome from these results is that it has been shown possible to make this TB analogue with the implemented method. Also, the result from the chromatography shows that the mix of TB diastereomers is separable by using dry column vacuum chromatography. These findings are valuable for further TB research. In addition, this work has resulted in useful TB analogues that can be used as building blocks for obtaining the heptakis TB analogue in the future. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/student-papers/record/9120395
- author
- Jakobsson, Emil LU
- supervisor
- organization
- course
- KASM05 20231
- year
- 2023
- type
- H2 - Master's Degree (Two Years)
- subject
- keywords
- Tröger's Base, Synthesis, Chromatography, Supramolecular chemistry, Diastereomers, Organic chemistry
- language
- English
- id
- 9120395
- date added to LUP
- 2023-06-09 09:07:08
- date last changed
- 2023-06-09 09:07:08
@misc{9120395,
abstract = {{Tröger’s Base (TB) is a bicyclic compound containing a methanodiazocine group between two aromatic rings. The methylene bridge forces the molecule to have a bent formation; thus, the aromatic rings are close to 90 degrees relative to each other, resulting in a rigid concave aromatic cavity. These unique properties make TB a great candidate as a molecular cleft compound and a good structure as a molecular receptor towards unfunctionalised molecules. The Tröger’s Base framework has therefore been found to be a useful building block in supramolecular chemistry. The Tröger’s Base project aims to complete a total synthesis of a linearly fused heptakis Tröger’s Base analogue. As a part of this project, the goals of this master thesis are to acylate the benzylic position of a TB analogue and to separate the resulting diastereomers with dry column vacuum chromatography. In order to achieve these two goals, six synthesis steps have been performed, starting from a commercially available aniline analogue. The aniline analogue was halogenated, followed by a condensation reaction to form the first TB analogue. After four more synthesis steps, including dehalogenation, Pd-catalyzed amination, amine protection, and acylation, where the benzylic position of a TB analogue finally functionalised. Afterwards, one of the diastereomers was successfully separated from the mix of diastereomers with a dry vacuum column using silica. As a result, this thesis work has shown it possible to acylate a TB analogue at the benzylic position and shown that the resulting mix of diastereomers is separable by dry column vacuum chromatography. In addition, the work has given valuable TB analogues, which can be used in further synthesis in the Tröger’s Base project.}},
author = {{Jakobsson, Emil}},
language = {{eng}},
note = {{Student Paper}},
title = {{A novel approach for functionalising and separating Tröger's Base Analogues}},
year = {{2023}},
}