As previously mentioned, one of the initial projects undertaken in this thesis work was to reproduce the synthesis of a BTA compound containing an amino acid linker and terpyridine end group, previously synthesised by Dr Savyasachi AJ of the Gunnlaugsson group. The purpose of this was to prove the reproducibility of the synthesis of this interesting compound,
Chapter 2. Benzene-1,3-5-tricarboxamide n-alkyl ester and carboxylic derivatives
to become familiar with the synthesis of tripodal compounds and to use as a model compound for microscopy training. The synthetic scheme of 66 is illustrated in Scheme 2.1. The first step in this scheme was the reaction between 4′-chloro-2,2′:-6,2′′-terpyridine with 1,3- diaminopropane to yield the amino-terpyridine derivative as shown in the scheme. This was achieved by reacting 4′-chloro-2,2′:-6,2′′-terpyridine with 1,3-diaminopropane at 125 °C for 24 h. Upon completion of the reaction, the reaction mixture was quenched with ice cold H2O
resulting in the formation of a white precipitate which was separated by filtration, re-dissolved in DCM and washed with H2O. The organic layer was then separated and dried over Na2SO4,
filtered and the solvent was removed under reduced pressure to reveal a white solid in 57 % yield. The amino-terpyridine was then coupled onto an alanine-derivatised BTA, using the conditions shown in Scheme 2.1, to result in 66. The solubility of this compound was investigated in a variety of solvents and then its self-assembly properties were probed using
Scheme 2.1 Synthetic scheme for the synthesis of 66, where (i) reflux at 125 °C for 24 h; (ii) DMF, DCM, EDC.HCl and HOBt, rt, 24 h.
66
64
Chapter 2. Benzene-1,3-5-tricarboxamide n-alkyl ester and carboxylic derivatives
SEM. In the PhD thesis of Dr Savyasachi AJ, he reported the effect of the linker on the self- assembly process of his family of amino acid based BTAs. In the case of a glycine linker, the material was found to gelate in a variety of solvents, however the chiral amino acid derivatives did not. They did, however, become viscous solutions when dissolved in various solvents, thus this was investigated further using SEM. These microscopy studies were carried out by drop- casting 5 µl portions of the various viscous solutions onto silica wafers, which were then dried under dynamic vacuum before being coated with a conductive Au/Pd layer and studied under SEM. Instead of the expected fibrous material, Dr Savyasachi observed the presence of microspheres, with different solvents and concentrations found to influence their size uniformity and distribution. This was repeated during this thesis work and the same results were
Figure 2.2 (a&b) SEM images of 66 in EtOH (scale bar left 10 µm, scale bar right 2 µm); (c&d) SEM of 66
Chapter 2. Benzene-1,3-5-tricarboxamide n-alkyl ester and carboxylic derivatives
obtained as demonstrated in Figure 2.2, where the results of the SEM carried out on dried samples of 66 in EtOH, MeCN and MeOH are presented. In the case of both EtOH and MeOH, the spheres were found to have various sizes, ranging from approximately 0.5 µm to 2 µm in diameter, while the MeCN samples were of more uniform size, approximately 2 µm in diameter. From this, it is clear that interactions with the solvent influence sphere size and that the moderate polarity of MeCN favours the formation of microspheres of a uniform size distribution. This work also illustrated the impact different amino acids can have on the self- assembly processes of related compounds. Further work was carried out by Dr Savyasachi AJ on the influence of a variety of metals on this derivative and other amino acid derivatives, however, this was not repeated during this thesis study.
2.2.2 Synthesis and characterisation of 68
Inspired by the interesting properties of 66, it was decided to synthesise a phenanthroline analogue, 68, seen in Scheme 2.2, to investigate if it displayed similar properties to those observed for 66. Phenanthroline was chosen as it has a different coordination requirement than terpyridine, thus it could potentially react with different metals than those used for the terpyridine derivatives studied by Dr Savyasachi AJ and due to the vast expertise in studying phenanthroline derivatives for a variety of purposes within the Gunnlaugsson group.122123
Scheme 2.2 Reaction scheme for the synthesis of 68, where (i) EDC.HCl, DMAP, DCM, argon, rt, 72 h.
Chapter 2. Benzene-1,3-5-tricarboxamide n-alkyl ester and carboxylic derivatives
After a number of attempts, 68 was successfully synthesised using a BTA derivative, 63, will be discussed in the next section, amino phenanthroline, 67, and the coupling reagents EDC.HCl and DMAP, stirring in DCM at room temperature in an inert atmosphere for approximately 72 h, a procedure adapted from that used by Dr Robert Elmes, previously of the Gunnlaugsson group.122 Once the reaction was complete, the solvent was removed under reduced pressure to reveal an orange oil, which precipitated to form an orange solid after the addition of H2O which was isolated by filtration. The product was an orange solid, that was
difficult to obtain in high yield and purity and quite insoluble in most common lab solvents, even at low concentrations and with the aid of heat and sonication. Some attempts were made to solubilise 66 in an attempt to gelate or crystallise the compound, however, these attempts were largely unsuccessful as shown in Figure 2.3. The solvents tested included MeOH, EtOH, IPA, H2O, C6H14, MeCN and CHCl3 and in most cases resulted in fibrous precipitates. SEM
was used to image the precipitates formed in the solvents of various polarities and the results obtained are shown in Figure 2.4. In the case of the one of the more polar solvents used, the morphology of the dried sample of 66 in MeOH looked like a dried film. In the case of the less polar solvents, the dried precipitates had a more fibrous-like precipitate and there was evidence of a small amount of spherical material, however, in most cases these were damaged or broke, as seen in Figure 2.4.Some metal salts were added to these gelation attempts and the effect of the addition of CuCl2 is seen in Figure 2.4, with the metal having very little effect on the
morphology of the material and also had no effect on the solubility of the ligand. Due to the synthesis, purification and solubility issues with this compound, further investigations were not pursued and instead we moved onto studying the family of structurally simple BTAs shown in Scheme 2.3.
Figure 2.3 Gelation attempts of 68, left to right, (i) 5mg in 0.5 mL MeOH; (ii) 5mg in 0.5 mL EtOH; (iii) 5mg in 0.5 mL MeOH; (iv) 5mg in 0.8 mL MeOH; (v) 5mg in 0.3 mL MeOH and 0.3 mL H2O; (vi) 5mg in 0.5 mL IPA.
Chapter 2. Benzene-1,3-5-tricarboxamide n-alkyl ester and carboxylic derivatives