Automation of organic synthesis has seen rapid progress in the past decade with the development of many platforms for execution, investigation and optimization of chemical reactions and multistep processes. Each of these platforms relies on a different approach to chemical synthesis; including traditional batch chemistry, solid-phase synthesis and flow chemistry, and uses a different dedicated hardware to translate and operate processes. The aim of this thesis was to identify both strengths and limitations of the existing synthesizers and to develop a new platform based on a hybrid approach that takes the best elements from each of them. First, the radial paradigm was established; a new arrangement of reaction modules that allows for their reuse within the same process, uses discrete volumes of solutions and decouples reaction steps so that each reaction in a multistep synthesis can be performed at optimal conditions, minimizing the waste of materials and equipment required (chapter 1, section 1.4). The hardware of the instrument is described thoroughly in chapter 2 with details of each module (broken down into its basic components), explanation of the possible flow pathways, troubleshooting and calibration data. Once the hardware was assembled, the radial synthesizer was validated by performing a series of showcase processes (chapter 3). First, convergent and linear syntheses of the active ingredient rufinamide were chosen to demonstrate the capability of switching between different synthetic routes without the need for physical rearrangement of the instrument (section 3.1). Second, a library of twelve derivatives was generated within a short amount of time and minimum waste of starting materials to show the potential of the radial synthesizer for a possible application in medicinal chemistry (section 3.2). Next, the synthetic and analytical capabilities of the instrument were expanded by integrating a module for photochemistry and flow-NMR spectroscopy via standard flow connectors (section 3.3). Finally, radial synthesis and continuous flow synthesis were compared by preparing three pharmaceutical ingredients (paracetamol, lidocaine, and nifedipine), developing and optimizing each step in the radial synthesizer and performing a scale-up in gram scale in a commercial continuous flow apparatus (section 3.4).
