Project Title: HETEROGENEOUS ORGANOCATALYSTS FOR THE GREEN SYNTHESIS OF CHIRAL GLYCIDATE INTERMEDIATES

Project code PNII-ID-PCE-2011-3-0041, No. 321/2011

Contracting Authority: UEFISCDI

Total funding: 1.350.000,00 lei

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 Summary

Project objectives:

O1, O5 and O6. The synthesis of homogeneous chiral ketones; The characterization of the homogeneous organocatalysts; The catalytic investigation of the prepared homogeneous organocatalysts (enantioselective epoxidation)

The difficulties encountered in the preparation of cis-cinnamic acid esters [L. Deng et al., J. Org. Chem. 57 (1992) 4320], lead to the necessity to find effective methods for the synthesis of (2R, 3S)-phenyl-glycidates by catalytic asymmetric epoxidation of the trans-methyl-cinnamate - much cheaper and commercially available. Due to the disadvantages associated with the use of the organometallic chiral complexes in such transformations, their replacement remains a challenging in the area. In this context, previous reports [JACS 1996, 118, 9806] recommend ketone derived from D-fructose (also known as ketone Shi) as a suitable candidate for the enantioselective epoxidation of a large number of di- and tri-substituted (E) –alkenes, (Z)- and terminal olefins in the presence of Oxone (potassium peroxomonosulfate). Reactions occur with enantioselectivities from high to moderate [J.Org. Chem., 2005, 70, 2904]. However, subsequent reports show that chiral ketone Shi derived from fructose is not effective for the epoxidation of α, β-unsaturated esters due to its decomposition tendency under required basic conditions. Moreover, Oxone undergoes a gradual decay in basic conditions. Therefore, creating and optimizing an organocatalytic system, able to transform the trans-methyl-cinnamate to optically active phenyl-glycidates, represented a challenge of the project.
    To achieve the project objectives an important amount of the research was dedicated to the optimization of the homogeneous organocatalytic system able to efficiently transform the trans-methyl-cinnamate to chiral phenyl glycidate through the dioxirane epoxidation (Scheme 1). For this, several ketone structures were synthesized (Scheme 2) and the reaction conditions were optimized for each, by using Oxone as epoxidation agent. The synthesis methodologies of A and B structures are described in the literature [Y. Tu et al., J. Am. Chem. Soc. 118 (1996) 9806; Catal. Sci. & Tech., 2015, 5, 729] while the procedure for the synthesis of C structure is detailed in the scientifically report of phase 1 of the project.

Scheme 1. Catalytic dioxirane-mediated epoxidation in the presence of Oxone

Scheme 2. Chiral ketones with different structures used for the dioxirane-mediated epoxidation of trans-methylcinnamate, in the presence of Oxone

Scheme 3. (A) Planar and spiro transition states for the olefine dioxirane-mediated epoxidation [Tetrahedron Lett., 1987, 28, 3311]. (B) Spiro transition states for dioxirane-mediated epoxidation of trans-methylcinnamate, in the presence of chiral ketone A (Scheme 2)

O2-O6. The synthesis of heterogeneous grafted organocatalysts. The characterization of the heterogeneous organocatalysts. The catalytic investigation of the prepared heterogeneous organocatalysts.

Table 1. Kinetic diameters of the organocatalysts, reactants and products, estimated from the molecular weight correlation [Combust. Flame 96 (1994) 163-170]

Scheme 4. Schematic synthesis procedure of the core-shell magnetic nanoparticles stabilized with silica or hydroxylated aluminium fluoride

In the following will be summarized the most important results obtained in the dioxirane-mediated epoxidation of trans-mehtylcinnamate in the presence of heterogeneous organocatalysts.

As specified, the immobilization of the organocatalysts generates heterogeneous catalysts with more complicated structures than homogeneous counterparts with unexpected positive or negative effects upon the catalytic efficiency. An important positive effect induced by the grafted ketone B (see Scheme 2) on aminopropyl-based MCM-41 carrier (characterized by a bi-modal porosity with narrow mezoporos of 2.6 and 3.6 nm, respectively), for instance, was the increases of the e.e. in the (2R, 3S)-phenyl-glycidate enantiomer. The catalytic activity was lower than that of the homogeneous ketone Shi (homogeneous Shi ketone (structure A, Scheme 2): C = 76.4%, S_epoxid = 54%, ee = 17.6% (2R, 3S); ketone B/MCM-41: C = 20.8%, S_epoxid = 35%, ee = 38.3% (2R, 3S)), but this is in line with the general features of heterogeneous versus homogeneous catalysis (ie, often the catalytic activity of solid catalysts is lower than of the homogeneous counterparts). The enhanced enantioselectivity arises, most probably, from steric congestion encountered by the prochiral reactant, namely trans-methylcinnamate (Scheme 5).

By using H₂O₂/CH₃CN mixture and in the presence of the ketone B/MNP-SiO₂ core-shell systems the conversion of the trans-methyl-cinnamate was quite high taking into account the reaction temperature: T = 0°C: C = 36.1%, S_epoxid = 100%, ee = 73.7% (2S, 3R). The total selectivity to epoxide indicates the system as a green one (Scheme 6). The stereoselection is very high in the presence of this catalyst but the discrimination is in the favor of the “wrong” enantiomer - (2S, 3R), indicating a reaction pathway through the “spiro 2” transition state (see Scheme 2). In the presence of the ketone B/MNP-AlF₃ sample, the trans-methyl-cinnamate conversions are lowered with 10% comparing with those obtained in the presence of the ketone B/MNP-SiO₂ core-shell system, while e.e. is 100% in the (2S,3R)-isomer regardless of the reaction conditions. These differences can have different reasons: i) the different chemical nature of the MNP shell (ie, SiO₂ versus AlF₃); ii) the lowered amount of the grafted chiral ketone; and/or iii) the higher particles agglomeration in the reaction medium of the ketone B/MNP-AlF₃ sample (DLS measurements). However, in both cases a great advantage of the system refers to the simple separation and recycling of the heterogeneous organocatalyst by applying an external magnetic force.

Scheme 5. Schematic representation of the trans-methylcinnamate epoxidation in the presence of ketone B/MCM-41 catalyst and Oxone

Scheme 6. Schematic representation of the trans-methylcinnamate epoxidation in the presence of ketone B/MNP/SiO2 catalyst and H2O2/acetonitrile

A considerable effort was invested in applying the concepts of green chemistry for developing a synthesis of heterogeneous organocatalysts with a high acceptability in the environment. For this, in the last part of the project have been developed new materials made from renewable organocatalysts intercalated into layered double hydroxides structure (LDH). In literature there is no information on the levulinate intercalation in LDH structures and their use in epoxidation reactions in liquid phase. On the basis of the materials design and of the catalytic system were major green elements such as simple preparation methodology from renewable raw materials, the heterogeneous character of the organocatalyst, the use of H₂O₂ as oxidizing agent and the lack of soluble inorganic base in the reaction medium. Moreover, the layered double hydroxides (LDH) are often preferred in chemical processes to other types of catalysts due to their versatility, simplicity, easy to modify their properties and low price. Such materials are an important basis for the development of new materials with controlled structure, controlled accessibility to the active sites, adjustable pore size and high surface area [Mat. Chem. Phys. 2007, 104, 133]. Not last, their ability to retain and change the inorganic with organic anions makes these materials unique.

Four types of heterogeneous organocatalysts were prepared by different methodologies, as listed in Table 2.

Table 2. Preparation methods for the levulinate-intercalated LDH

The prepared materials were characterized by techniques such as adsorption-desorption isotherms of liquid nitrogen at -196 ° C, X-ray diffraction (XRD), thermogravimetric analysis and differential thermal analysis (TG-DTA), and infrared spectroscopy.

Anion exchange process occurs with the introduction levulinate anions in LDH structure in different concentrations and structural orientations, depending on the method of preparation (Table 1).

IR spectra of LEV@LDH-N₂ sample highlight the characteristic absorption bands of the LDH carrier and a novel band with a maximum at 1567 cm^-1 associated with the asymmetrical vibration of ionized carboxyl groups of the levulinate molecules. This band, which is missing in the IR spectrum of the LEV@LDH-air sample is the main evidence that [LEV]^δ- species were inserted by ion exchange only in nitrogen atmosphere. The intercalation is also confirmed by TG-DTA analysis. Levulinic acid content of the sample was measured from TG as 14.5wt%. The XRD pattern of the sample does not indicate changes in structural parameters of the pristine LDH, while adsorption-desorption isotherms of liquid nitrogen indicate changes its texture properties: surface BET slightly decreases from 42 m²/g (MgAl-LDH) to 39 m²/g (LEV@LDH-N₂), while the porosity has been change from a bimodal with pores of 3.5 and 14.6 nm (MgAl-LDH) to a monomodal one with pores of 10.6 nm (LEV@LDH-N₂). Summarizing these data it can be supposed the [LEV]^δ- species are not intercalated between the LDH sheets but, most probably, are anchored on the sheets corners of the LDH (Figure 1). This assumption is also based on the fact that due to high load density of carbonate anions between layers they are in a strong electrostatic interaction with LDH layers, making difficult any ion exchange with species outside the network [Chem. Mater. 13 (2001) 3507-3515].

Figure 1. Schematically LEV@LDH-N2 structure (D) based on the characterization results obtained from DRIFT spectroscopy (A), TG-DTA (B) and XRD (C)

Co-precipitation methodology leads to materials in which some of the carbonate groups were replaced with levulinate anions. In this case, the XRD diffraction clearly indicates the existence of two types of anionic species between layers LDH: carbonate and levulinate. Notable is that both (003) and (006) diffraction lines correspond to two different distances d_00l, showing that anionic species occupy different volumes. Moreover, the intensity of the diffraction lines corresponding the phases containing levulinate species indicates a high quantity of these species intercalated into the LDH material. The shift of the reflection line from (003) to ​​lower 2θ values corresponds to a widening of the gallery space (d₀₀₃) from 7.77 Å (characteristic to MgAl-LDH) to approx. 7.95 Å (characteristic LEV@LDH-pp), corresponding to a height of about 3.15 Å gallery. It is clear that this space is large enough to accommodate a carboxyl group but not all levulinic acid in a perpendicular position to the layers of LDH (kinetic diameter of 6.0 Å, see Table 1). As such, it is more likely a partial penetration of the levulinate species between the LDH galleries. But it can not be ruled out an intercalation of levulinic acid structures in parallel position to the LDH sheets. Such intercalation is supported not only by X-ray diffraction but also by the adsorption-desorption isotherms of liquid nitrogen. Thus, the BET surface of the sample LEV@LDH decreases to 11 m²/g. At the same time the average size of the large mesopores decreases from 14.6 nm to 6.3 nm while the narrow mesopores with a size of 3.5 nm existing in MgAl-LDH were not evidenced (Figure 2). Indeed, in this case, the amount of grafted/intercalated levulinic acid in the LDH structure, is much higher (22.4 wt%), as determined from measurements TG/DTA, explaining the high decrease in both the BET specific surface area and the mesopore size.

The presence of the levulinate groups into the LDH structure was also confirmed by IR spectra. Although a low intensity, the presence of the bands at 1626 and 1586 cm^-1 indicates the intercalation in the form of levulinic acid R-COOH, where H⁺ is ionized in the space between the layers as C(O)O^δ-H^δ+. The band centered at 1720 cm^-1, characteristic of free levulinic acid, shows that not all the amount of levulinic acid was converted into the levulinate species but on the LDH surface exists in two distinct forms: ionized and non-ionized.

Figure 2. Schematic structure of the LEV@LDH-pp sample (D) based on the characterization results from XRD (A), adsorption-desorption isotherms (B) and IR spectroscopy (C)

A comparison of the experimental results obtained in homogeneous catalysis and heterogeneous phase synthesis demonstrates again the successful synthesis of the two types of materials listed above. In homogeneous catalysis, in the presence of [Na][LEV] as organocatalyst, the conversion of trans-methylcinnamate reaches s 22.4% with a total selectivity (100%) in phenyl-glycidate, after 24 hours at 40°C. Very similar values ​​are obtained in the presence of the LEV@LDH-pp sample (C = 21.4%, S = 100%), while in the presence of the LEV@LDH-N₂ sample, the conversion of methyl-cinnamate not exceed 4% with a selectivity in phenyl-glycidate of about 87%, after 18h. Obviously, in the case of solid samples, the concentration of organocatalyst species is much smaller than in homogeneous systems, but their dispersion on the surface seems to favor the epoxidation reaction. Importantly, the reactions in the presence of LEV@LDH samples were carried out in the absence of an inorganic base, required in homogeneous phase, bringing a major advantage in terms of environmental protection. Also, the the total (100%) selectivity in phenyl glycidate and the use of a benign oxidizing agent (hydrogen peroxide instead of Oxone) are other reasons favorable to use of such catalytic systems.

In our best knowledge, this is the first example of using levulinic acid as an organocatalyst and not as renewable raw material for the synthesis of added value compounds. This way, the use of this valuable renewable raw material can be greatly extended.

An outstanding feature of metal-organic-framework (MOF) structures is their great structural and functional diversity that is achieved by chemical modification of organic linker or inorganic cluster. The synthesis of chiral metal-organic frameworks (CMOFs) is possible via the assembling of chiral organic ligands with metal ions [Chem. Commun. 2006, 701]. Unfortunately, the direct incorporation of a sophisticated homochiral ligand into the scaffold has two major drawbacks: i) the use of long organic ligands often reduces the diameter of the pores and thus reduces the accessibility of the reagents to the catalytic sites, and ii) keeping the chiral activity of the catalyst inside the porous network is a critical point [J. Am. Chem. Soc. 2010, 132, 14321].

A difficulty in the use of this concept as a platform for the synthesis of different heterogeneous chiral catalysts is the adjustment of the synthesis conditions of every new organic linker that can often be time-consuming and highly non-trivial. An attractive alternative approach that can circumvent these limitations is the postsynthetic modification of MOFs [Chem. Soc. Rev. 2009, 38, 1315]. Post-synthetic functionalization of MOFs with chiral entities was reported as well [J. Am. Chem. Soc. 2009, 131, 7524]. Certainly, this approach has some challenges, such as: i) the introduction of a functional group in a scaffold that can serve as an anchoring point for the covalent attachment, ii) the use of a structure that provides apparently a high surface area and, most importantly, presents accessible large open channels. They can be preserved even after the postsynthetic introduction of the active sites. A good thermal and chemical stability is also very challenging.

In this context, MOFs (eg, MIL-101(Al), MIL-101(Al)-NH₂ and UIO-66(Zr)-NH₂) modified with chiral ketones (structure A and C, Scheme 2) obtained from cheap renewable raw materials as D-fructose or synthetic chemicals such as acetyl, benzoyl or pivolyl chloride were envisaged. For this, two methodologies were applied: physical (encapsulating) and chemical (grafting through covalent bonds) immobilization.

Physical immobilization offers several practical advantages such as: (i) does not require the modification of the commercially available organocatalysts, used in homogeneous catalysis; (ii) the methods used are simple and effective; (iii) does not require additional costs, making this method very attractive to potential industrial applications.

Through physical immobilization four samples, denoted C-MIL-101(Al)-T, C-MIL-101(Al)-NH₂-T, C-MIL-101(Al)-U and AL-MIL-101(Al)-T (where: C – chiral ketone Shi (structure a from Scheme 2), AL – levulinic acid, T – thermal treatment, U-ultrasound treatment) were synthesized.

The DRIFT spectra of the MOF carrier and the organocatalysts-based MOFs indicate the homogeneous chiral ketone Shi was, indeed, encapsulated in the MOF pores (C-MIL-101(Al)-T and C-MIL-101(Al)-U samples) through the presence of the band located at a wavenumber of 1710 cm^-1 (νC=O (ketone)) (Figures 3 and 4).

Figure 3. DRIFT spectra of the MIL-101(Al)-T and C-MIL-101(Al)-T samples	Figure 4. DRIFT spectra of the MIL-101(Al)-U and C-MIL-101(Al)-U samples

Indeed, the catalytic results shows that the epoxidation of the trans-methyl-cinnamate in the presence of the C-MIL-101(Al)-T and C-MIL-101(Al)-U samples take place, at 0°C, which high selectivities (up to 100%) to epoxide and e.e. of 7-10% in the (2S, 3R)-isomer, for conversions of trans-methyl-cinnamate of 2-4%.

Obviously, lowered catalytic activity is due to not to the mass transfer limitations of the reactants/products throughout the MOF pores (MIL-101 structures are characterized by the existence of two mesoporous cavities with diameters of 29 and 34 Å, accessible through pentagonal and hexagonal windows (12 and 16 Å, respectively) [Science 2005, 309, 2040]) but to the low reaction temperature. Nevertheless, it is expected the presence of the chiral ketone and the reactant in the mezopores, both with high kinetic diameters, some structural restrictions to appear preventing the organocatalyst to adopt the spatial configuration required for an efficient chiral induction. This has as effect the lowering of the e.e. (7-10%). Moreover, the low excess in the opposite (2S, 3R) phenyl-glycidate isomer can be, again, explained through the “spiro 2” transition state which seems to be favored during the reaction.

Diacetate ketone (structure C, Scheme 2) encapsulated in MIL-101 structure lead at conversions of 10-25% for 100% selectivity to epoxide, at 24°C. Extremely important, e.e. not only increased at 30-40% but it was in the favor of (2R, 3S)-phenyl glycidate, suggesting a preference for the “spiro 1” transition state. Obviously, the absence of the ketal ring from the chiral ketone structure and therefore the lack of the steric constrains favors this reaction pathway. Increasing the reaction temperature from 24 to 50°C causes a further increase in trans-methylcinnamate conversion (40%) while both the selectivity to epoxide and e.e. to (2R, 3S)-phenyl glycidate remain at the same level. However, these results are superior to the previously. The two encapsulated chiral ketones are schematical represented in Figures 5 and 6.

Figure 5. Enantioselective epoxidation of trans-methylcinnamate in the presence of chiral ketone Shi/MIL-101 structure	Figure 6. Enantioselective epoxidation of trans-methylcinnamate in the presence of diacetate chiral ketone Shi/MIL-101 structure

Through chemical immobilization (grafting through covalent bonds) several other samples, denoted as PSM1, PSM2, PSM3, PSM4, and PSM5, were prepared. For creating covalent bonds in the final catalysts, MOF's with amino terephthalic acid pillars (UIO-66(Zr)-NH₂, structure with octahedral and tetrahedral cavities of 11.0 and 8.0 Å, respectively and windows of 6.0 Å) and a range of acid chlorides such as acetyl chloride (kinetic diameter of 5.8 Å, PSM1, 60°C) benzoyl chloride (kinetic diameter of 6.9 Å, PSM 2, 60°C and PSM4, 100°C) and pivolyl chloride (kinetic diameter of 6.6 Å, PSM3, 60°C and PSM5, 100°C) were used (Figure 7, exemplification for PSM2 sample). IR spectra of the PSM samples displays specifically absorption bands of covalently grafted organic molecules (Figures 8 and 9), demonstrating their successful synthesis. Post-synthetic modification takes place with high yields, as a function of both organic molecule nature and temperature: PSM1 – 72%, PSM2 – 35%, PSM3 – 5%, PSM4 – 63%, PSM5 – 46%. Closed value to the reported ones [Chem. Mater., 26 (2014) 6722] proves the method reproducibility.

Figure 7. Post-synthesis modification of the UIO-66(Zr)-NH2 with benzoyl chloride at 60°C

Figure 8. IR spectra of PSM1 (acetyl), PSM2 (benzoyl) and PSM3 (pivolyl) based samples (temperature synthesis: 60oC)	Figure 9. IR spectra of PSM4 (benzoyl) and PSM5 (pivolyl) (temperature synthesis: 100oC)

Although organic species grafted in MOF structure are neither chiral nor from renewable raw materials, synthesized materials has the advantage (i) of an extremely simple methodology, (ii) ruled in the absence of any volatile organic solvent, (iii) fast (10 min), and (iv) efficient (up to 72% yield) in agree with [Chem. Mater., 26 (2014) 6722]. Although preferred, due to much larger cavities in the structure, MIL-101(Al)NH₂ could not be used in the post-modification due to its low chemical stability and high reactivity of acid chlorides.

Interesting enough all organic molecules used in the post-modification have been linked by -NH₂ of the solid material pillars with higher or lower yields even if only acetyl chloride posses a kinetic diameter smaller than that of the triangular window opening (5.8 versus 6.0 Å) in the MOF's structure. These results show that MOF's structure is flexible when used molecules with a diameter greater than triangular window opening, especially at high temperatures [Chem. Mater., 26 (2014) 6722]. Extremely important, this flexibility does not cause damage to the crystal structure, as shown by X-ray diffraction measurements, the crystallinity of the post-modified samples remaining unchanged.

Part of synthesized materials has proved to be highly selective to epoxides (95-100%) even if the conversion of the trans-methyl-cinammate did not exceeded 8.0%. The reactions were carried out under green conditions, by using a benign oxidizing agent, such as hydrogen peroxide and with a low consumption of energy (0-24 °C).

If in the case of MIL-101(Al) – based organocatalysts the catalytic efficiency could be highly improved by optimizing the reaction condition and encapsulating the proper chiral organocatalyst, in this case the narrow pores of the carrier (11.0 and 8.0 Å) did not allowed these improvement. As it is already specified, both reactant and products are large molecules, with kinetic diameters of 6.7 Å (trans-methylcinnamate) and 6.9 Å (phenyl-glycidate). Even if the mass transfer of such large molecules is possible at higher temperatures throughout the MOF porosity (due to the structure flexibility) the existence of the organocatalysts inside the PSM pores induce steric hindrances high enough to prevent the formation of the transition state structure, a high part of the reactant being practically untransformed. To this should be added the temperature restrictions at which the epoxidation reaction can be conducted higher temperatures leading to a non-selective decomposition of the hydrogen peroxide. However, the synthesis materials could be successfully used for the epoxidation of smaller molecules.

In conclusion, the objectives in the project proposal have been totally achieved. The carried out research activities allowed the creation and optimization of organocatalytic heterogeneous systems capable of transforming the trans-methyl-cinnamate in (2R, 3S)-phenyl-glycidate with high e.e., by catalytic dioxirane-mediated epoxidation. Such an approach is considered, at present, a green challenging alternative to current methods of phenyl-glycidate intermediates synthesis, extremely valuable in producing pharmaceuticals, agrochemicals and a high number of fine chemicals with value-added on market outlets.

An alternative to such systems, has been the development of active and selective organocatalytic heterogeneous systems for the synthesis of the (⁺_-)-phenyl-glycidates which, through the simplicity of preparation from cheap, available and renewable raw materials, could offset any additional costs required for the separation of racemic mixture in corresponding enantiomers. Levulinic acid, for example, one of the Top 15 platform molecules is used as a precursor for pharmaceuticals, plasticizers, and is recognized as an important raw material for the manufacture of a large number of potential chemical compounds and biofuels. The works carried out in the project and especially the positive obtained results provides for the first time a new opportunity for the use of levulinic acid as a raw material in the synthesis of new solid materials with catalytic applications.

Another current concern of green chemistry is related to the use of volatile organic compounds as solvents. In this context, ionic liquids are often recommended as a benign alternative, due to their low volatility which leads to the elimination of major pathways to be released into the environment and contamination. However, this property is different of toxicity. Unfortunately, in many cases, the aquatic toxicity of ionic liquids is at least as severe as that of most organic solvents. A really green process based on ionic liquids should consider their benign character for environment. Thus, the use of structures derived from biomaterials often leads to a high biodegradability. In this context, [Na][LEV] can be classified as an 100% biodegradable and low toxicity ionic liquid. Besides these benign attractive properties, the obtained results recommend [Na][LEV] as an effective organocatalyst for the dioxirane-mediated epoxidation of trans-methylcinnamate with a high deficient in electrons. However, due to limitations on mass transfer in ionic liquids, chemical industry prefers using solid catalysts. Therefore, their combination with porous solid materials is highly preferred because of the ease of separation of the IL with the solid support.

Dissemination:

ISI Papers:

    1. A. Negoi, K. Teinz, E. Kemnitz, S. Wuttke, V. I. Parvulescu , S.M. Coman, Top Catal (2012) 55, pp. 680–687;

    2. N Candu, S. Wuttke, E. Kemnitz, S. M. Coman, V. I. Parvulescu, Pure Appl. Chem., (2012) 84, pp. 427–437.

    3. S. Wuttke, A. Negoi, N. Gheorghe, V. Kuncser, E. Kemnitz, V. Parvulescu, S.M. Coman, ChemSusChem. (2012), 5, pp. 1708-11.

    4. N. Candu, D. Paul, I.-C. Marcu, V. I. Parvulescu, S. M. Coman, Levulinate-intercalated LDH: a potential heterogeneous organocatalyst for the green epoxidation of α,β-unsaturated esters, Catal. Today, (2016), accepted, under evaluation

    5. N. Candu, S. Wuttke, M. Tudorache, V. I. Parvulescu, S. M. Coman: Ketone postsynthetic modification of MOF’s: efficient heterogenous organocatalysts for epoxidation reactions, Chem Commun, 2016, in work

Communications:

1. N. Candu, M. Tudorache, T. Trotus, K. Kranjc, M. Kocevar, S. Wuttke, V. Parvulescu, S. Coman, “Catalysis in Organic Synthesis” Conference, Moscow, Russia, 15-20 September, 2012

2. S. Wuttke, A. Negoi, N. Candu, N. Gheorghe, V. Kuncser, E. Kemnitz, V. I. Parvulescu, S. M. Coman, XI^th European Congress on Catalysis (EUROPACAT), Lyon, France, 1-6 September, 2013

3. C. Rizescu, N. Candu, M. Tudorache, V. I. Parvulescu, S. M. Coman, The 6^th Asia-Pacific Congress on Catalysis (APCAT-6), Taipei, Taiwan, 13-17 October, 2013

4. N. Candu, C. Rizescu, M. Tudorache, V. I. Parvulescu, S. M. Coman, 25^th Organic Reactions Catalysis Society Meeting, Tucson, AZ, USA, March 2-6, 2014

5. M. Tudorache, G. Ghemes, A. Gheorghe, S. Coman, V.I. Parvulescu, International Conference on Green Chemistry and Sustainable Engineering, Barcelona, Spain, July 29-31, 2014

6. D. Paul, N. Candu, C. Rizescu, I. C. Marcu, M. Tudorache, V. I. Parvulescu, S. M. Coman, 12^th European Congress on Catalysis – EuropaCat-XI, Kazan, Russia, 30 August – 4 September, 2015

7. N. Candu, C. Rizescu, I. Podolean, M. Tudorache, I. C. Marcu, S. Wuttke, V. I. Parvulescu, S. M. Coman, The 11^th International Symposium of the Romanian Catalysis Society (ROMCAT 2016), Timisoara, Romania, 06-08 June, 2016