Ultrafast poly (disulfide) synthesis in the presence of organocatalyst

Abstract

Scientists frequently seek out more usable, efficient, and practical approaches as the chemistry develops. A minimum amount of solvent, a short amount of time, and mild conditions are necessary for this purpose. The versatility of the study that needs to be done is viewed as a benefit. In light of all of this, disulfide has been studied for a very long period of time. Fundamentally, great progress has been made in recent years in the synthesis of novel sulfur-containing polymers and in the modification of some large types of polymers' characteristics through the incorporation of sulfur or polysulfide moieties. As can be observed from the significant number of studies focused polymers containing sulfur, these novel synthetic processes have frequently produced substantial polymeric materials. As a result, interest in this topic has been considerably improved. In order to expand the technological range of application of these materials, recent academic and applied research has concentrated on enhancing the characteristics and processing properties of these materials. Dynamic disulfide bond is used in a wide variety of applications because it can be used to manipulate reversible covalent chemistry in response to external stimuli. These applications include controlling protein conformations, mediating cellular redox homeostasis, cellular delivery of drugs, biomolecules and liposomes, dynamic self- assembly, self-healing materials, inorganic/organic hybrid polymers, reprocessable vitrimers, CO regulation, and Li-S batteries. This adaptability of disulfide chemistry in materials has been a beacon for synthesizing polymers that containing disulfides. They have also become ideal platforms for medicine, thanks to their dynamic and reversible properties and their response to stimuli such as reductants, light, heat, and mechanical force. Subject to all these properties, polymers with repetitive disulfide bonds in the main chain have long proven to be extremely useful in the fields of chemistry, pharmacology and etc. The synthesis of polydisulfide has a date that began in 1944 with Patrick and his colleagues. After the first polydisulfide was obtained by oxidation polymerization, polydisulfide was prepared with using many different methods. The synthesis methods of polydisulfides are classified according to the monomers that are used: oxidative step growth polymerization with dithiols, ring-opening polymerization with cyclic disulfides, and polymerization with linear disulfides. These include interfacial polymerization, polymerization methods classified under click chemistry, living/controlled polymerization, polycondensation reactions, and Michael addition polymerizations. Mitsunobu reaction is named after Oyo Mitsunobu, discovered in 1967. Mitsunobu reaction is an organic synthesis method that provides various functional groups such as esters from the alcohols in the presence of triphenylphosphine and azodicarboxylates such as diethyl azodicarboxylate (DEAD) or diisopropyl azodicarboxylate (DIAD). Despite the fact that DEAD and DIAD are the most frequently used azodicarboxylates, there are a number of others that can be employed that make the workup and/or purification process simpler and, in some situations, allow for the use of more basic nucleophiles. The synthesis procedure occurs by mixing phosphine with azodicarboxylate until a white precipitate develops at -10 °C, and the reaction medium is often THF or toluene. The alcohol and phosphine combine to generate a strong leaving group, which is then replaced by the nucleophile in a stereochemistry reversal reaction in the traditional SN2 style. When the azodicarboxylate takes the place of the leaving group as opposed to the intended nucleophile, a characteristic byproduct is created. This occurs when steric or electronic restrictions prevent the nucleophile from being sufficiently acidic (pKa>>13) or nucleophilic enough. On the other hand, Camp and Jenkins investigated how to synthesize triphenylphosphine sulfide under Mitsunobu conditions. They presented the finding that triphenylphosphine was regenerated by reductive elimination and yielded a disulfide to the literature after evaluating all the preliminary results. This study, inspired by the work of Camp and Jenkins, an organocatalyst-mediated, extremely fast, robust, and practical poly(disulfide) synthesis method is presented to polymer chemistry. While trying the find optimum conditions for polydisulfide synthesis, kinetic studies were carried out using various organocatalysts, initially commercially available 1,6-hexane dithiol and diisopropyl azodicarboxylate (DIAD) in order to find the best catalyst. Remarkably, all catalysts studied yielded poly(disulfide) at low to high molecular weights within 1 minute, despite using a very low amount of catalyst (5%). According to experimental studies, triphenylphosphine (PPh3) was selected as the suitable catalyst for the long time period and 1 minute after kinetic measurements and was used to determine the optimum conditions for polymerization. Although polydisulphides obtained by using different solvents were successfully obtained, chloroform gave the best results among these solvents in terms of both reaction medium and solubility. Then, in the studies carried out to determine the reaction condition, it was observed that the amount of catalyst we determined gave the best results when 1% and 10% per equivalent molar of the organocatalyst were used. In addition to the mentioned studies, concentration, temperature and equivalent conditions were also studied. As a result of all these kinetic experiments, optimum conditions were determined. Various dithiol compounds were polymerized and the corresponding polydisulfides showed molecular weights ranging from 2.37 to 85.6 kDa. Various polydisulfides with different properties have been successfully prepared using optimum conditions. A "catalyst-free" method of poly(disulfide) synthesis was also tried. It has been shown that while low molecular weight polymers are obtained at room temperature, high molecular weight polymers can be obtained by increasing the reaction temperature to 60 °C. The resulting polymers were characterized using spectroscopic methods such as 1H-NMR, 13C-NMR, FT-IR, GPC, and DSC, and the results revealed that the DIAD-derived hydrazine unit was incorporated into polymer chains as an end capping agent. As a result of the analyzes, it has been shown that the thermal behaviors of the polymers belonging to the analog series, which differ only in terms of carbon number, exhibit different melting temperatures according to their crystalline characteristics. In addition, the most important feature of disulfide bonds is their cleavage by reduction. Taking advantage of these properties, a depolymerization study was carried out on a model poly(disulfide) using dithiothreitol as the reducing agent. As a result of its simplicity of operation, fast character, and ability to be carried out in mild conditions, it is thought that the presented strategy holds great promise for the synthesis of poly(disulfide). Additionally, believed that synthetic polymer chemistry will inspire great interest in the straightforward poly(disulfide) synthesis method.