Synthesis and thermal properties of bisamides

The synthesis of all bisamides described here was done by the technicians Jutta Failner and Sandra Ganzleben under my supervision. A detailed synthesis protocol for each compound is provided in the experimental section. They also performed basic analytic procedures like ¹ H-NMR and TGA for each compound under my supervision. Analysis and interpretation of the corresponding data was carried out by me.

For the symmetrically substituted benzene bisamides 2, 4A, 4B and 4C, a facile one-step synthesis was selected, as it is shown schematically in Figure 20. 1,4-phenylenediamine was reacted with the respective acid chloride in THF as solvent. To remove HCl formed during the reaction, an acid scavenger like triethylamine or pyridine was added. This synthesis is similar to the one of the 1,4-trans-cyclohexane bisamide 1, which has been reported in literature.⁶³

To successfully synthesize the asymmetrically substituted bisamides 3A, 3B and 3C, three steps were necessary, as shown in Figure 21. In the first step, the tert-butyl-substituent was attached to a 4-nitroaniline core. Next, the nitro-group was reduced with H₂ using palladium on activated charcoal as catalyst to obtain the corresponding amine group. In the third step, the respective fluorocarbon acid chloride was reacted with this amine group to finally obtain the asymmetric bisamides.

Figure 20: Schematic synthesis of the symmetrically substituted benzene bisamides 2 and 4A - C

After synthesis, all bisamides were purified by crystallization from methanol, ethylacetate or THF. All bisamides were obtained as crystalline white solids in good yields, which are listed in Table 1.

Table 1: Yields of 1,4-benzene bisamides after crystallization. For asymmetric bisamides, the relative yield takes only the last step of the synthesis into account.

compound 2 3A 3B 3C 4A 4B 4C

rel. yield [%] 77 64 20 84 94 43 81

Molecular characterization and purity of all synthesized bisamides was determined by NMR and mass spectroscopy. The respective data for each compound are given in the experimental section.

The thermal behavior of the synthesized 1,4-benzene bisamides was evaluated by means of TGA and DSC. This is important, as in this work self-assembly is mostly done upon cooling of hot bisamide solutions in this thesis. The thermal characterization is necessary to ensure the stability of the bisamides under these conditions, e.g. at 120 °C when using o-DCB as solvent.

TGA curves of all applied bisamides are displayed in Figure 22. The TGA curve of the reference bisamide 1 is given in the experimental section. Apparently, all investigated bisamides are thermally stable up to at least around 210 °C. All of them show a one-step

3A n = 2 3B n = 4 3C n = 6 Figure 21: Schematic synthesis of asymmetrically substituted bisamides 3A - C.

mass loss from 100% to 0%, which is indicative for an evaporation of the compounds rather than a decomposition process. The curves of 2 and 4A feature very little kinks around 90%

mass. Therefore, the temperature at 5% mass loss is applied as TGA temperature. These temperatures are provided in Table 2. The TGA of bisamide 1 reveals a one-step mass loss during heating with 10 K/min under N2. A weight loss of 5% is reached at 267 °C. The benzene bisamide 2, which comprises no fluorine, is the most stable material with 5% mass loss at 295 °C. All three compounds of series 3 show a mass loss of 5% at the same temperature, namely at 221 °C.

For later self-assembly experiments it is also important to know about the phase behavior, especially melting and crystallization temperatures, because melting during self-assembly

50 100 150 200 250 300 350

Figure 22: TGA curves of all seven investigated 1,4-benzene bisamides. Measurements were performed with a heating rate of 10 K/min under N2.

experiments may result in a system with two liquid phases. In such systems, assembly may occur in a phase with larger bisamide content, which is detrimental to a proper self-assembly investigation. Thus, the thermal transitions of the compounds were measured via DSC. The results are shown in Figure 23 alongside with those of the reference bisamide 1.

The fluorine-free bisamides 1 and 2 melt above 270 °C. By contrast, all six fluorine containing bisamides melt between 200 and 250 °C. Upon cooling, 2 crystalizes at 265 °C, which is at a much higher temperature than all other bisamides investigated. Notably, bisamide 1, which features the same substituents, shows no sharp crystallization peak. Here, crystallization occurs in a broad range around 160 °C, which is scarcely visible in the cooling curve. All bisamides of series 3 and 4 crystallize between 190 and 220 °C.

For comparison, Table 2 lists melting and crystallization temperatures of the compounds.

The discrepancy between the decomposition temperatures of the TGA and the melting temperatures of the DSC Tm can be explained by the different procedures of the two methods. In particular, the DSC measurements were performed in a high-pressure pan, preventing the compounds from evaporation as it takes places in the TGA, where additionally a significant nitrogen flow of 75 mL/min is applied. In the sealed pan applied in DSC, the bisamides of series 3 also melt in a close temperature range from 221 to 226 °C.

Measurements were performed with a heating/cooling rate of 10 K/min in a sealed high-pressure pan.

crystallizing at the highest and 3B at the lowest temperature. So, in this series, no trend of T_C with increasing fluorocarbon chain length is apparent. In series 4, temperature at 5% mass loss increases with the length of the substituent from 212 °C for 4A to 235 °C for 4C.

Contrary to this, T_m and T_C exhibit another pattern: 4B features lowest T_m and TC, while 4A and 4C melt and crystallize roughly at the same temperature. Most interestingly, this pattern with the compound bearing a fluorinated C5-chain providing lowest TC of the series is the same as in series 3. Yet, to prove this rule, investigation of more compounds would be necessary, which is beyond the scope of this work.

Table 2: Thermal properties of all seven 1,4-benzene bisamides investigated. The 1,4-cyclohexane bisamide 1 is listed for comparison. Temperatures at 5% mass loss were taken from TGA measurements under N₂. Peak melting (T_m) and crystallization (T_c) temperatures and melting enthalpy (ΔHm) were measured by DSC in a sealed pan. T_m and ΔH_m were determined during second heating and T_c was measured during first heating.

Heating and cooling rate was 10 K/min for all measurements.

Compound M [g/mol] T5% mass loss [°C] T_m [°C] ΔH_m [kJ/mol] T_c [°C]

1 282 267 272 6.4 ~ 160

2 276 295 281 32.5 265

3A 388 221 226 3.8 213

3B 488 221 226 9.8 194

3C 588 221 221 11.0 203

4A 500 212 225 38.9 219

4B 700 216 215 58.7 206

4C 900 235 228 61.6 219

To sum up the results from thermal characterization, all eight investigated bisamides are thermally stable beyond 200 °C and do not melt upon heating in this range. Therefore, they all appear suitable for self-assembly upon cooling from hot solutions, at least, as long as the temperature of the hot solution does not exceed 200 °C.

The thermal characterization of each individual compound is also provided in the compound data sheets in the experimental part.