A two-step synthetic method was used to prepare the tetralactam series (1a-4c, Scheme 1, a). An additional step was required to produce the 5-(trifluoromethyl)isophthalic acid starting material from the 3-methyl-5-(trifluoromethyl)benzoic acid precursor through KMnO4 oxidation in H2O (100 °C) before treatment with HCl (1 M) over ice to yield the desired intermediate. A previously reported substitution reaction was then used to produce the isophthaloyl chloride intermediates from the isophthalic acid starting materials in CH2Cl2, with two drops of DMF added as a catalyst with oxalyl chloride. The isophthaloyl chloride intermediates were used immediately without workup. Residual oxalyl chloride was removed, and the flask was charged with dry CH2Cl2 and anhydrous tetrabutylammonium chloride (TBACl), which acted as a templating agent. The appropriate diamine was dissolved in dry CH2Cl2 and added dropwise to the reaction mixture over 10 min. As the macrocyclisation reaction occurred, partial precipitation of the product and side products occurred. The reaction was stopped at 10 min with the addition of either CH3OH or by removal of the reaction solvent under reduced pressure. Short reaction times were employed to yield the kinetic [2+2] macrocycles preferentially over larger thermodynamic side products. A series of solvent washes and triturations were performed to isolate the desired products before anion exchange was performed by stirring the crude products with KPF6 in dry CH3CN. The bound Cl -anion was exchanged with the weakly coordinating PF6 -anion, which was removed using excess H2O to provide the pure tetralactams in yields ranging from <1% to 39% (Scheme 1, a). Despite the low yields of macrocyclization in the current work, we anticipate future improvement of the syntheses by using the dynamic covalent approach developed by Mastalerz and coworkers. Additionally, two previously reported acyclic compounds, 5 and 6, were synthesised, which are structurally related to tetralactam 2a (Scheme 1, b and c). Isophthalamide 5 was synthesised according to a modified method by Ishikawa et al. (Scheme 1, b). The isophthaloyl chloride intermediate was prepared and then dissolved in dry CH2Cl2. Aniline was then added dropwise to the reaction mixture, producing a precipitate. The precipitate was filtered and washed with CH2Cl2 and n-hexane, then resuspended in CHCl3:H2O (1:1, v/v) with HCl (1 M). The desired product was then collected in the organic phase, dried over MgSO4, and evaporated to isolate isophthalamide 5 in a 51% yield. Benzamide 6 was synthesised following the previously reported method by Costa et al., where the o-phenylenediamine was first dissolved in dry CH2Cl2 before the dropwise addition of 3-fluorobenzoyl chloride. The precipitate was collected and washed with CH2Cl2 and H2O to isolate 6 in a 33% yield. For further synthetic methods, see the experimental procedures section, or for information regarding compound characterisation and associated spectra (Figure ), see the electronic supplementary information (ESI).