Structural systematics is a multidisciplinary approach in structural science that involves a comprehensive analysis of structurally related compounds. The main concept of structural systematics is the comparison of chemical structure data, usually derived from single crystal or X-ray powder diffraction, with physical properties of structurally similar compounds (salts, complexes and small organic molecules). From this idea we have developed in Chapter 2, a 2×6 isomer grid of difluorobenzamides (F2-xx) and (xx-F2) as investigated by integrating crystal structure analyses, gas phase calculations and conformational analyses. All isomers aggregate via N–H⋯O=C intermolecular interactions and usually in combination with intermolecular C– H⋯O/F/π interactions and often with F⋯F contacts. Expanding benzamide derivatives to di-amides increases the possibility of pharmacological activities. The X-DIP compounds were therefore synthesised and characterized by spectroscopic techniques and X-ray diffraction as detailed in Chapter 3. Halogens (X) influence the aggregation in crystal structures by varying interactions especially halogen bonding. These compounds were further reacted to form two novel groups of amideimide and di-amide isomers. Substitution of the di-amides with ethyl esters at the ortho-, meta-, and para- positions provide the x-Est-DIP and x-Est-PYR derivatives, in Chapter 4, that potentially increases the number of interaction sites and also enforces a change in the molecular geometry. The pyridine (2/3/4-Est-PYR) derivatives typically bind to water molecules by strong N–H⋯O hydrogen bonding interactions. From this research, substituted pyridine/pyrimidine rings in the (x-N2)2-PYR diamide system are explored in Chapter 5. Pyridines and pyrimidines are substantial precursors of many biomolecules and have chemical and biological applications. The presence of water molecules tends to impart quite different chemical and physical properties and their crystal structures display several interesting features. Finally, di-imide macrocycle products combining 3 or 4 (x-IO3 and x-IO4) rings are discussed in Chapter 6 in order to maximise the highest possible yields and develop the most effective synthetic strategies and procedures.