Synthesis of azobenzene-functionalized molecular glasses

3.2.1 Synthesis of the azobenzene side-groups

In this work, the azobenzene chromophores are synthesized via a synthesis route known as the

“Mills reaction”: A condensation reaction of a para-nitrosobenzoic acid and an aniline derivative.

Unlike in the common synthesis route towards azobenzenes, which involves the diazotization of an aniline derivative requiring strict temperature control, the educts in the Mills reaction are stable at room temperature and the reaction can be performed as a one-pot synthesis. Two different approaches were used to synthesize the azobenzene moieties depending on the availability of the aniline derivatives with different substituents. The reaction with the individual steps of the synthesis route towards the azobenzene chromophores is depicted in Figure 7.

Figure 7: Reaction scheme of the synthesis of azobenzene moieties used to synthesize the targeted azobenzene-functionalized molecular glasses.

In both cases, 4-aminobenzoic acid is dissolved in dichloromethane (DCM). To this solution, an aqueous solution of K⁺[HSO5]^-, and oxidative persulfate, is added at room temperature under vigorous stirring. The reaction progress is monitored via thin-layer chromatography. When the reaction is finished, the oxidized product, a nitroso derivative, is filtered off and dried under vacuum. As small impurities of the nitro compounds formed by the oxidation of the amines do not interfere the Mills reaction to azobenzene, no purification step is necessary at this stage of the synthesis.^[90]

The first route includes a Mills-reaction with a commercially available aniline derivative bearing methoxy- or CF3 substituents, and the chlorination step to the corresponding acid chloride, which is used for the synthesis of the molecular glasses. In detail, in a first step, the Mills reaction is carried out at room temperature, in which the nitrosobenzoic acid condensates with the amine derivative in presence of an acid (AcOH) for about 48 h to yield the azobenzene derivative. The methoxy-azobenzene product could directly be subjected to the chlorination step after a purification step via recrystallization in EtOH.

The second route includes a Mills-reaction with an iodine-substituted aniline derivative, an esterification step, an “Ullmann reaction”, a deprotection step and a final chlorination step. In detail, in a first step, an azobenzene derivative with an iodine at the para-position is generated via Mills reaction of 4-iodoaniline with the para-nitrosobenzoic acid under the same conditions as in case of the methoxy- and trifluoromethyl substituted derivatives. Before the conversion of the synthesized para-iodine-substituted 4-(phenylazo)benzoic acids, the acid has to be converted to the corresponding ethyl ester. After the esterification reaction, the formed iodine-substituted 4-(phenylazo)benzoic acid ethyl ester is subjected to a copper-catalyzed Ullmann coupling reaction with a perfluoroalkyl iodide derivative featuring the iodine at the end of the perfluoroalkyl chain.

The nucleophilic aromatic substitution reaction is performed at 100 °C and is nearly quantitative.

After a purification step, the azobenzoic acid ester can be converted to an acid again and then be subjected to the chlorination step. Chlorination of the acids is performed with oxalyl chloride, since the excess of the chlorination compound can readily be removed under high vacuum.

3.2.2 Synthesis of the molecule cores

In this chapter, eleven different molecular glasses based on three different molecule cores are investigated. As the two triphenylamine-based molecular glasses have been synthesized by R.

Walker and as the 6,6´,7,7´-tetrahydroxy-4,4,4´,4´-tetramethylbis-2,2´-spirobichroman molecule core is commercially available, only the synthesis of the molecule core of the 1,3,5-benezenetrisamide-based is discussed in detail.

For the synthesis of the 1,3,5-benzenetrisamine, 3,5-dinitroaniline is reduced with palladium on activated charcoal (Pd/C; 10% Pd) in a solvent mixture of THF/MeOH. The reaction is stirred at 35°C in an autoclave with a H2 pressure of 3.5 bar for 24 h. Afterwards, the catalyst is filtered off and the solvent is evaporated under reduced pressure. The dried product needs no further purification.

Since the product is sensitive to oxidation, it has to be stored under inert gas.

Figure 8: Reduction of 3,5-dinitroaniline to 1,3,5-benzenetrisamine.

3.2.3 Synthesis of the molecular glasses

In a final step, the activated, i.e. chlorinated azobenzoic acid derivatives were attached to the 1,3,5-triamino benzene or the tetra-functional spirobichromane core in an amidation or an esterification reaction, respectively. Prior to the amidation reactions of the azobenzene derivatives with the triamino benzene core, a 3,5-Dinitroaniline was reduced to the tri-functional amino derivative using palladium on active carbon in a high-pressure reactor at a pressure of 3 bar overnight. After thorough drying of the educt under high vacuum the core is ready for the amidation reaction. The spirobichromane core was used as received, but also was dried under high vacuum at 60 °C overnight prior to the esterification. Figure 9 depicts the reaction scheme of the conversion of the azobenzene derivatives with the respective molecule cores to yield the azobenzene-functionalized molecular glasses.

Figure 9: Reaction scheme of the conversion of azobenzene derivatives with the respective molecule cores to yield the azobenzene-functionalized molecular glasses.

To avoid oxidation of the azobenzene acid chloride derivative, the amidation reaction of the 1,3,5-benzenetrisamine with the respective azobenzene acid chloride derivative to yield the azobenzene-functionalized 1,3,5-benzenetrisamide-based molecular glass is carried out under inert atmosphere in dry solvents and flame-dried Schlenk flasks. In a first step, the azobenzene acid chloride derivative is dissolved in dry NMP, to which dried LiCl is added to increase the solubility of the resulting molecular glass. As base, an excess of triethylamine is used. To reduce the reaction speed

the solution is cooled down to 0°C prior to adding 1,3,5-triaminobenzene to the reaction mixture.

The reaction mixture is then carried out at room temperature for 24 h. The reaction can be monitored by TLC. The crude reaction products could be purified using one or more of the typical purification methods of organic chemistry, e.g. column chromatography or re-crystallization.

As in case of the amidation reaction, the esterification reaction of the 6,6´,7,7´-tetrahydroxy-4,4,4´,4´-tetramethylbis-2,2´-spirobichroman with the respective azobenzene acid chloride derivative is carried out under inert atmosphere in dry solvents. In a first step, the azobenzene acid chloride derivative is dissolved in dry THF, to which dried LiCl is added and an excess of triethylamine is added. To reduce the reaction speed the solution is cooled down to 0°C prior to adding the spirobichromane core to the reaction mixture. The reaction mixture is then carried out at room temperature for 24 h-48 h. Also here, the crude reaction products could be purified using one or more of the typical purification methods of organic chemistry, e.g. column chromatography or re-crystallization.

The esterification of the triphenylamine to yield the azobenzene-functionalized triphenylamine-based molecular glasses was carried out by R. Walker (University of Bayreuth) according to Y.

Shirota et al..^[91]