Development of novel palladium-containing catalysts on the basis of nanostructured polymers in hydrogenation and cross-coupling reactions for production of biologically active compounds
The increasing needs for production of the chemical and pharmaceutical and food industry demand development of new methods of obtaining of biologically active compounds. Reactions of selective catalytic hydrogenation (and selective hydrogenation of alkynols, in particular) are the basis of a number of existing syntheses. For example, product of 2-methyl-3-butyne-2-ol (MBY) hydrogenation (2-methyl-3-butene-2-ol (MBE)) can be further used to produce dehydrolinalool (DHL), selective hydrogenation of which results in formation of linalool (LN) – one of the most widely used terpene alcohols. One of the routes to LN production is acetylenic process. High space-time yields at reasonable selectivities (i.e., avoiding overhydrogenation) are required for the design of an efficient and economic process of obtaining of ethylene alcohols (e.g., MBE, LN, isophytol (IP)). About a half of worldwide LN production is reckoned to be made through chemical synthesis while the rest is produced from natural plant terpenes. Most of produced LN (more than 95%) is used as a fragrance or flavouring agent. Moreover, LN can be regarded as a basic material for a very large range of other terpenoids. It can be converted to terpineol, geraniol and citral, and used in the preparation of citronellol, the ionones, farnesol and sesquiterpenes. Synthesis of fat-soluble vitamins (E and A) usually not involve LN, but its precursor DHL. The industrial method of alkynol hydrogenation is based on the use of Lindlar catalyst (Pd/CaCO3 modified with lead acetate and quinoline), which provides selectivity about 95% at 100% of conversion. Modification of Pd surface with quinoline was proposed to influence the polarization of the Pd-H bond due to the possible electron donation. Besides, it can compete with alkyne for adsorption and prevent polymerization and isomerisation processes. However, the use of these modifiers leads to pollution of target product that is inadmissible in pharmaceutical industry. In spite of numerous data on the MBY hydrogenation, it is still a challenge to achieve high selectivity in hydrogenation of terminal alkynes. On the other hand, the analysis of all possible factors influencing the alkene selectivity (the ability to form a certain hydride phase, the preferential alkyne adsorption, definition of small ensembles in order to reduce oligomerization), the size of Pd nanoparticles seems to be the key factor of a triple bond hydrogenation. At the same time, another challenge is to provide high stability of catalytically active Pd nanoparticles, as carbonization of palladium surface as well as sintering and leaching of nanoparticles often cause the loss of catalytic activity and selectivity at multiple reuses. It is noteworthy that during the development of new effective catalytic systems the use of nanostructured polymers as supports causes increasing interest. Polymers as supports are able to provide control over the particle size and their monodispersion that is the main problem of synthesis catalytically active metal nanoparticles. Besides, polymers have variety of properties (existence of functional groups, molecular weight, crosslinking degree, hydrophilicity or hydrophobicity, etc.), varying which it is possible to influence effectively processes of nanoparticle formation. Cross-coupling reaction is of the second importance in fine organic synthesis. Suzuki cross-coupling between aryl halides and arylboronic acids is one of the most widespread and effective methods of synthesis of biaryl, which are important semi-products in synthesis of pharmaceuticals, ligands and polymers. There are more than three hundred various commercial compounds which can react Suzuki. Suzuki reaction gives possibility to produce compounds possessing strong pharmacological activity which are rarely found in nature. In the case of reaction of Suzuki cross-coupling, which is also catalyzed by Pd, at present the most perspective catalysts are systems on the basis of Pd nanoparticles or complexes stabilized by polymers. However, in spite of success achieved in some cases, common disadvantage of heterogeneous, heterogenized and quasi-homogeneous catalysts of Suzuki reaction is loss of catalytic activity as a result of palladium leaching. The molecular forms of palladium formed in situ were considered as the most active ones, and though the complete prevention of Pd leaching is mechanistically impossible, it should be minimized. Besides, the disadvantage of many catalytic systems including polymer-stabilized Pd nanoparticles is the necessity of addition of phase transfer agent in order to achieve high activity in Suzuki reaction proceeding in aqueous medium. Proposed approach is based on the use of porous matrix of hypercrosslinked polystyrene (HPS) as a support for synthesis and stabilization of palladium nanoparticles. Among the organic porous supports, HPS, which is obtained by chemical incorporation of methylene groups between the neighboring phenyl rings in the polystyrene homopolymer solution in dichloroethylene or in a gel-like poly(styrene-p-divinylbenzyl) copolymer received increased attention. Due to its high crosslinking degree, which can be higher than 100%, HPS consists of rigid cavities (pores), the size of which can be varied depending on the reaction conditions. The unique property of HPS is the ability to swell in different solvents, which favors inclusion of various organometallic compounds in the HPS matrix. The existence of the pores of a standard size and shape allows controlling the metal particle growth. HPS-based catalysts allow control of the nanoparticle formation due to a “cage” effect (by limiting the nanoparticle size with the pore size) along with controlling the precursors and reduction conditions. It is noteworthy that HPS is commercially available. Another advantages of HPS are high thermal (up to 300oC), chemical and functional stability. It is noteworthy that HPS matrix also provides excellent stability of the catalytic systems due to the preventing of metal species dissolving and leaching. The above mentioned advantages of HPS make possible the multiple repeated use and regeneration of the developed catalysts. In general, the advantages of developed HPS-based catalytic systems in comparison with existing industrial catalysts include: (i) large specific surface area (usually near 1000-1500 m2/g); (ii) possibility to work in virtually any solvent; (iii) high catalyst activity at lower metal loading due to formation of well-defined nanoparticles vs. their aggregation in conventional catalysts; (iv) higher stability and lifetime due to the minimization of metal loss; (v) high selectivity without necessity to use catalytic poisons and metal-modifiers; (vi) high activity without necessity to use phase transfer agents; (vii) prevention of nanoparticle aggregation during the reaction. Thus for the development of HPS-based catalytic systems, we used various HPS (non-functionalized and HPS bearing amino-groups). Besides, the nature of the metal precursor was varied to design nanoparticulate catalysts containing monodisperse nanoparticles. Catalysts based on HPS were synthesized by wet impregnation method followed by reduction of metal compounds. It is noteworthy that the impregnation method is simple in implementation, does not require complex laboratory equipment, does not need the use of the inert atmosphere (due to the high stability of HPS (chemical and thermal), and also palladium precursors). During the synthesis of polymer-containing HPS-based catalysts, the choice of a precursor is important. Depending on the precursor nature, it is possible to obtain catalysts with different distribution of active metal in the polymeric matrix that leads to formation of nanoparticles of different diameters. It is due to the hydrophobic nature of HPS matrix, which often does not allow hydrophilic metal precursor (acid or salt) to penetrate deeply into the polymeric network. During the catalyst synthesis, various precursors were used (PdCl2, Pd(CH3COO)2, (CH3CN)2PdCl2, (PhCN)2PdCl2, ((Sty)(CH3CN)PdCl2) and (Sty)2PdCl2) to control nanoparticle size and size distribution. Besides, metal loading and reduction method were varied (liquid-phase or gas-phase reduction). Unreduced catalysts, as a rule, show higher activity in cross-coupling reactions. However the development of effective catalyst on the basis of preliminarily created nanoparticles is possible. Therefore the question of a choice of the reduction method of metal catalyst is also important. In case of catalytic hydrogenation, liquid-phase reduction, which allows varying the rate of nanoparticle nucleation and, therefore, their diameter, is preferable. However, in view of the fact that the HPS possesses high thermal stability, gas-phase reduction in hydrogen flow, which is the most preferable in case of Suzuki reaction, is also possible. Thus in the case of the use of gas-phase reduction method in hydrogen flow, it is necessary to know the limits of temperature stability of the chosen polymer. In order to find the thermal stability of HPS polymeric matrix, thermogravimetric analysis of the polymeric matrix, which was pretreated and crushed up to sizes of granules less than 60 microns, was carried out. It was revealed that HPS is stable up to 300°C in argon medium; however, at higher temperatures the destruction takes place with the loss of about 60% of weight. Thus, the HPS-based catalysts can be reduced in hydrogen flow at a temperature 300°C without the risk of destruction of polymer structure. It was also found that for successful catalyst synthesis, initial HPS should be pretreated, to avoid the presence of inorganic impurities (Fe3+, Cl-) and to achieve low humidity (less than 2%). Thus the optimal procedure for HPS pretreatment was developed. This procedure was clarified from the point of view of support leaching, and it was found that no leaching of HPS takes place. To exclude internal diffusion limitations and to provide higher surface area HPS should be powdered before the use as support. As a result it was found that the use of HPS having granules size smaller than 60 µm is optimal.