The thesis is devoted to the development of new catalytic systems for efficient heterogeneous hydrogenation of quinoline derivatives.
The influence of the composition and characteristics of Ni-containing composites obtained by pyrolysis of the Ni complex with melamine on aerosil, on the selectivity and yield of products in the processes of hydrogenation of quinoline and furfural with hydrogen gas was studied. Even though the studied composites are inferior to Pd-containing analogues in terms of the yield of hydrogenation products, their use can be justified considering significantly lower cost and toxicity.
Two composites based on MIL-101(Cr) carrier bearing Ni and Pd nanoparticles were studied in quinoline hydrogenation reaction. The robust procedure for the generation of the active catalytic species was developed via in situ reduction of Ni(II) by NaBH4 and Pd(II) by hydrogen. Use of both composites allowed to prepare 1,2,3,4- tetrahydroquinoline with more than 90 % yield, but in the case of Ni-containing catalyst this result was achieved at 8 times higher metal loading in the reaction mixture.
However, despite higher activity of Pd/MIL-101(Cr) compared to NixB/MIL-101(Cr), the latter could be more attractive for the chemical industry due to cost efficiency. It was shown that pyrolysis of Co(II) complexes with 1,10-phenanthroline (Phen), melamine (Mel) and 1,2-diaminobenzene (DAB) on SiO2 (Aerosil) resulted in the formation of the composites, containing metallic Co nanoparticles and N-doped carboneous particles. None of the factors studied (content of C, N, Co, N/C ratio, parameters of Raman spectra or XPS), was the sole factor that controlled the activity of the catalyst in the hydrogenation of quinoline. The three most active composites
were selected for scale-up and hydrogenation of a series of substituted quinolines. It was shown that increasing the load to 50 grams of quinoline has no effect on the yield. The target product 1,2,3,4-tetrahydroquinoline was obtained with the yields 89%, 96%
and 97% for Co-Phen/SiO2-1, Co-Mel/SiO2-4 and Co-DAB/SiO2-2, respectively, on the 50 g scale (100 bar H2, 100 °C, 24 h, 3 mol % of catalyst in methanol). The scope and limitation of the reaction for different types of substituents in benzene or pyridine
rings were studied. It was shown that the substituents in the pyridine ring significantly decrease the substrate activity for hydrogenation. Even in the case of the simple methyl group, the reaction needed harsher conditions and the yields were lower. Substituents in the benzene ring did not have such a strong effect. Several unusual cases of catalytic hydrogenation and hydrogenolysis reactions, using commercially sourced heterogeneous Pd-containing catalysts, from our practice in the High-pressure Synthesis Laboratory (Enamine Ltd.) were described. In general, complications we faced were of three types: (1) irreproducibility of the procedures; (2) chemoselectivity issues; (3) undesirable Pd-catalyzed defunctionalization reactions. In turn, these complications led to an increase in production costs, and loss of time and resources.
The decomposition of Pd2(dba)3 on readily available Norit GSX charcoal was investigated. As a result of numerical experiments, the optimal scalable and reproducible conditions for the preperation of the catalyst were finally found (with the addition of stearic acid in dioxane at 100 ºС and the use of Norit activated carbon as a carrier), which made it possible to scale up the synthesis and obtain a 500 g. Additives of stearic acid contribute to the formation desired size of nanoparticles and their stabilization on the surface of the composite.
The obtained catalyst application demonstrated its high tolerance to functional groups, which made it possible to successfully obtain several hydrogenated derivatives of quinoline, isoquinoline, as well as to expand the limits of the catalyst's application to other classes of organic compounds. Next, the range of substrates is expanded to include other functional groups and fragments. The use of the obtained catalyst for reduction of nitro and nitrile groups, debenzylation of phenols and primary aliphatic amines, hydrogenation of double bonds and dehalogenation was successfully demonstrated. Among the exceptions, it is worth noting unsuccessful attempts to
debenzylate secondary amines. The obtained catalyst was used in the industrial process of Enamine Ltd. The successful hydrogenation of nitrogen-containing heterocyclic acids, nitro- and nitrile functional groups, as well as reductive amination were
performed. Thus, the efficient and selective synthetic procedures for preparation of a number of diamines, heterocyclic N-containing carboxylic acids and aliphatic amino acids as valuable building blocks for pharmaceutical chemistry were elaborated.
