Streamlining Organic Synthesis - Accessing Cycloparaphenylenes and Azobenzenes via Advanced Synthetic Techniques

Abstract

The synthesis of organic molecules can be a challenging and tedious task. These compounds, which are not necessarily large or complex, may require long, multi-step syntheses. This hampers research and complicates access to important drugs or new materials. Over time, strategies have been developed towards shorter, more efficient, and faster accesses to molecules of interest. Since the purification of substances accounts for a huge part of the work, so-called one-pot reactions were developed, which combine successive reactions without intermediate purification. In the first part of this thesis, a one-pot reaction has been developed for the substance class of cycloparaphenylenes (CPPs). Their synthesis is usually achieved by a multi-step process, which relies on the combination of smaller building blocks. The developed method provides rapid and selective access to CPPs with different ring sizes via the in-situ formation of macrocyclic precursors and their subsequent aromatization in a single flask. However, this method is only suitable to obtain small amounts of these compounds. To provide access to large amounts of different sized and functionalized CPPs, key building blocks for their synthesis have been prepared using continuous flow chemistry. Self-built reactors were optimized and utilized to obtain substance quantities on up-to kilogram scale. By this, the investigation of known and novel CPPs and related macrocycles is no longer limited by multi-step syntheses and the resulting small amounts of material. Continuous flow chemistry can not only be used to produce large quantities of a compound but can also be applied to safely handle a hazardous substance. The critical compound will only exist in small quantities at a time and is safely contained inside the flow reactor. This feature was utilized to synthesize different non-symmetric substituted azobenzenes (ABs) via a Baeyer-Mills reaction. The toxic nitrosobenzene was accessed in a continuous flow reactor and allowed to react immediately. By this, multiple substituted ABs were obtained in a fast and safer way, compared to traditional (multi-step) batch synthesis.