Project Title: NOVEL HETEROGENEOUS CATALYTIC SYSTEMS BASED ON IONIC LIQUIDS AND ORGANOCATALYSTS FOR ASYMMETRIC EPOXIDATIONS

No. 8/2012, project code PN-II-CT-ERC-2012-1

Financial Authority: UEFISCDI

Project Host Institution:

Host Institution: University of Bucharest

Address: Bdul Mihail Kogalniceanu, 36-46, Bucharest 050107, ROMANIA

City: Bucharest

Institutional Code in the Register of Potential Contractors (http://rpc.ancs.ro):1716

Research team

Project phases and fundings

Phase 1: 02.07.2012-15.12.2012; 214.748,7 lei

Phase 2: 16.12.2012-15.12.2013; 1.060.616, 25 lei

Phase 3: 16.12.2013-01.07.2014; 224.635,05 lei.

Total funding: 1.500.000,00 lei-24 months (02.07.2012-01.07.2014).

Objectives

The specific objectives of the project were:

O1. Screening of the ionic liquids in organocatalytic asymmetric epoxidation (months 1-3).

O2. Bi- and triphasic ionic liquid based systems in organocatalytic asymmetric epoxidation (months 2-11).

O3. Synthesis and characterisation of SILP based organocatalysts (months 13-19).

O4. Catalytic tests in the presence of heterogeneous SILP based organocatalysts: the epoxidation reactions (months 14-24).

Project Summary

The application of asymmetric catalysis in organic synthesis is an effective way of obtaining laborious molecular structure, following the concept of atom economy. The chiral organometallic complexes have been the first system of this kind, developed to meet the needs of chemical industry. Unfortunately, such systems, often prepared with expensive ligands, are disabled during the chemical process, introducing major limitations in the development of industrial syntheses which use them. As such, in recent decades, scientists have begun to look for solutions in the development of much cleaner and safer methodologies. In this context, organocatalysis start to gain importance in large increasingly by the benefits it brings in terms of both economic and environmental protection. On the other hand, taking into account the green chemistry concepts and current constraints on the use of volatile organic solvents, finding "green" alternative to this is another area of ​​current research in chemistry.

In this context, the main objective of the project was to find and develop green alternatives based on the use of ionic liquids (IL) and organocatalysts, for the asymmetric epoxidation of trans-methyl cinnamate to optically active phenyl-glycidate. These compounds are used as important intermediates in the synthesis of numerous drugs. Difficulties of preparation of cis-cinnamate esters are well known to researchers in this field. Therefore, there is a real need for finding effective methods for the synthesis of (2R, 3S)-phenyl glycidates by catalytic asymmetric epoxidation of trans-methyl cinnamate - which is much cheaper and commercially available.

The screening of the ionic liquids showed that e.e. values vary in the range of 7.6 – 62.3%, increasing in the following order: CH₃CN<[EMIM][CF₃SO₃]<[BMIM][BF₄]=[MBPy][BF₄] <[BMIM][PF₆]=[MMPIM][(CF₃SO₂)₂N)]<[EMIM][(CF₃SO₂)₂N)] ([MMPIM]=1,2-dimethyl-3-propyl imidazolium). A further increase of the e.e. of phenyl-glycidate was recorded in the presence of a co-solvent such as methanol, probably due to reduced viscosity (as such due to increased mass transfer). Reactions carried out in ionic liquids show a variation of the selectivity to glycidate in a range of 56-87.3%, in order: [BMIM][BF₄] < [EMIM][O₃SCF₃] < [BMIM][PF₆] = [EMIM][(CF₃SO₂)₂N)] < [MMPIM][(CF₃SO₂)₂N)], demonstrating that epoxidations in IL solvents depend on many factors such as their polarity, hydrophobicity and coordination ability.

In the context of using ionic liquids as reaction medium in such reactions, an important aspect of the project was to study the distribution phase, establishing a protocol for the efficient separation and recycling of the homogeneous organocatalysts. Both e.s. and catalytic activity slightly decreases when recycling the ionic liquid phase (together with the organocatalyst) probably due to the degradation of part of the organocatalyst in the used reaction conditions.

This study, along with studies that have shown the beneficial involvement of H₂O₂/AcCN mixture in the catalytic cycle, have resulted in an efficient biphasic system to achieve asymmetric epoxidations by using IL/AcCN (soluble in IL)/hexane (immiscible with IL) phase, useful for creating heterogeneous systems based on IL (SILP and SILC), in the next stage of the proposed study.

The methodology of the IL grafting on solid surfaces is an important factor influencing both the catalytic properties and chemical stability of the heterogeneous organocatalyst. Therefore, the immobilization of chiral ketone into the IL grafted by covalent bonds (SILC) on the solid carrier lead to materials with high catalytic performances (e.g., high conversions and e.e.) in the asymmetric epoxidation of the trans-methylcinnamate ester while the IL immobilization by its physisorbtion on the solid surface (SILP) resulted in materials with lower yields and e.e.. Moreover, in the latter case, there was a massive leaching of both the organocatalyst and the IL from the solid surface during the catalytic reaction. Contrarily, SILC type samples were founded to be more stable, allowing recycling 4 catalytic cycles without significant loss of yield or e.e.

Given the obvious influence not only of the IL chemical properties but also of the physico-chemical properties of the carrier upon the catalytic behavior, the last but equally important step was to optimize the prepared solid catalytic materials and the reaction conditions. The concept of the MNP based materials preparation was based on two important studies: i) the study conducted in IL /volatile organic solvent systems and SILC/SILP system, and ii) the successful development of the biocatalytic hybrid materials based on MNP that served as model for the current catalytic systems. Therefore, it was taken into account the use of a third type of solid carrier - magnetic nanoparticles (MNP) - stabilized by their coating with silica (SiO₂@Fe₃O₄) or by placing them in multi-walled carbon nanotubes (MWCNT@ Fe₃O₄). On these NMP based carriers were further attached by covalent bonds ILs with basic character (SBILC), in which the organocatalyst was previously immersed.

The characterization of the prepared materials allowed establishing the physico-chemical structure - catalytic activity - enantioselectivity correlation. Therefore, the novel developed heterogeneous organocatalysts SBILC@MWCNT@Fe₃O₄ showed a relatively high efficiency for the asymmetric epoxidation of the cheap trans-methylcinnamate to chiral (2R, 3S)-phenyl glycidate (X = 55-62%, S_glycidat = 90-94% and e.e._{(2R, 3S)}=100%). The development of these catalysts answer to the principles of green chemistry and sustainable development through economic benefits and environmental protection they bring. Furthermore, the use of heterogeneous organocatalysts in asymmetric catalysis could bring important benefits of industrial segments such as pharmaceuticals, food, agrochemical, etc. On the other hand, taking into account the constraints on the use of volatile organic solvents, finding a green alternative represents another area of ​​current research in chemistry, with major implications in all industrial sectors.

The research team involved in the scientific work included, besides two experienced researchers, two Postdocs, a PhD student and two master’s students. Due to the technical complexity involved, the project has provided an environment for individual development of the co-opted students who had a predominant participation in the project. One example is the opportunity the students had to use the research infrastructure available in the catalysis group, made up of a series of high-performance devices for characterization of solid materials, which is extremely important in their training as future professionals in the field of chemistry, in general and catalysis, in particular.

Dissemination

Scientifically impact of the research conducted during the project is proven by the acceptance of two papers for publishing in European Journal of Chemistry Central and Catalysis Science & Technology and four communications at international conferences in the field:

Papers

1. Tudorache, M., Ghemes, G., Nae, A., Matei, E., Mercioniu, I., Kemnitz, E., Ritter, B., Coman, S., Parvulescu, V. I., Central European Journal of Chemistry, 12 (2014) 1262-1270

2. Candu, N., Rizescu, C., Podolean, I., Tudorache, M., Parvulescu, V. I., Coman, S. M., Catal. Sci. & Tech., 2014, DOI: 10.1039/C4CY00891J

Communications

1. Natalia Candu, Loredana Protesescu, Kristof Kranjc, Marijan Kocevar, Simona M. Coman, ORCA Meeting COST, Marseilles, France, 29-30 Martie 2012 (Oral Presentation)

2. E. Kemnitz, V. I. Parvulescu, S. M. Coman, IUPAC 8^th International Conference on Novel Materials and Synthesis (NMS-VIII) & 22^ed International Symposium on Fine Chemistry and Functional Polymers (FCFP-XXII), Xi’An, China, 14-19 October 2012 (Invited Lecture)

3. A. Negoi, F. Savu, M. Tudorache, S. M Coman, V. I. Parvulescu, 10^th International Symposium of the Romanian Catalysis Society ROMCAT, Cluj-Napoca, Romania, 29-31 Mai, 2013 (Poster)

4. M. Tudorache, G. Ghemes, S. Coman, V.I. Parvulescu, Kick-off Workshop, Action CM1303 SysBiocat, Madrid, Spain, 10-11 April 2014 (Poster)