2.1 General

Styrene, 3-tert-butil salicylaldehyde, trioxane, 3,5-di-tert-butil salicylaldehyde, (1R,2R)(- diaminocyclohexane, N-Methylmorpholine-N-Oxide (NMO) and Pyridine-N-Oxide (PyNO) were supplied by Sigma-Aldrich. NaHCO₃, toluene chloroform and dichloromethane were purchased of Merk. Na₂SO₄ and methanol were acquired of J. T. Baker. Finally, glacial acetic acid and ethanol were acquired of Fluka and Panreac, respectively. Thermo Scientific Nicolet is50 FT-IR Spectrometer with attenuated total reflectance was used for obtaining the infrared spectra. Thermo Scientific Evolution 300 UV spectrometer was used for acquired the UV-vis spectra. Varian CP-3800 chromatographic equipment was used for quantification of the reaction products using a B-Dex chiral capillary column (length 30 m, I.D 0.25 mm, film thickness 0.25 µm).

2.2 Catalyst synthesis

The synthesis procedure of dimeric homochiral Mn(III)-Schiff base was the result of the combination of the following steps: first, synthesis of the dialdehyde ligand [³⁶], then synthesis of the Schiff base ligand [³⁷] and finally the synthesis of the dimeric ligand and the catalyst according the method established by Kureshy et al [³⁵].

Synthesis of 5,5-methylene-di-3-tert-butyl salicylaldehyde (Dialdehyde Ligand) 1

Synthesis of dialdehyde was carried out with a minor modification to the reported method by Janssen et al [³⁶]. In a typical experiment, a solution of 3-tert-butyl salicylaldehyde 73.8 mg (4.14 mmol) and trioxane 11.7 mg (1.3 mmol) in 10 ml of glacial acetic acid was heated to a temperature of 90-95 °C under nitrogen atmosphere. A mixture of concentrated sulfuric acid and glacial acetic acid (0.32/0.68 ml/ml) was dropwise added. The temperature of resulting solution was maintained for 24 h. Subsequently, the reaction mixture was poured into cold water and allowed to stand overnight. The precipitated solid was filtered and extracted with hexane (30 ml). The solvent was removed under vacuum at 68 °C, resulting in dialdehyde as a reddish yellow solid in 40% yield.

Synthesis of N-(2-hydroxy-3,4-di-tert-butyl benzaldehyde)-1-amino-2-cyclohexeneimine (Schiff Base) 2

Synthesis of the chiral Schiff base was carried out with a minor modification to the reported method [³⁷]. In a typical procedure, 3,5-di-tert-butyl-2-hydroxybenzaldehyde (3.02 mmol) and (1R,2R)(−)diaminocyclohexane (3.02 mmol) were stirred in chloroform at 0 °C for 12 h, and then the mixture was warmed up to room temperature. The solvent was removed under vacuum at 60 ºC and unreacted starting materials were removed by washing with water leading to the formation of the “half unit” Schiff base as a yellow solid in 84% yield.

Synthesis of 5,5-methylene di-[(R,R)-{N-(3-tert-butyl salicylidine)-N’-(3’,5’-di-tert-butyl salicylidene)}-1,2-cyclohexanediamine] (Dimeric Ligand Schiff Base) 3

A solution of 5,5-methylene-di-3-tert-butyl salicylaldehyde (0.478 mmol) in ethanol was mixed with Schiff Base (0.956 mmol) in dichloromethane. The resulting mixture was refluxed for 8-10 h. The excess solvent was removed by vacuum and then precipitated out the chiral ligand as a greenish-yellow solid in 80% yield.

Synthesis of 5,5-methylene di-[(R,R)-{N-(3-tert-butyl salicylidine)-N’-(3’,5’-di-tert-butyl salicylidene)}-1,2-cyclohexanediaminato (2-) manganese(III) chloride] (Dimeric Catalyst) 4

0.20 mmol of dimeric ligand Schiff base dissolved in dichlorometane was mixed with 0.40 mmol of manganese acetate tetrahydrate dissolved in methanol under an inert atmosphere (N₂). The reaction mixture was stirred for 12 h, and subsequently, was cooled to room temperature. Subsequently, 0.40 mmol of lithium chloride was added and the resulting mixture was stirred while exposed to air for 5 h. The solvent was removed under vacuum and the evaporation residue was recrystallized in dichlorometane leading in homochiral dimeric catalyst as a brown solid in 90% yield. A general scheme of the synthesis of dimeric catalyst is summarized in Figure 1.

Figure 1 General scheme of the synthesis of dimeric catalyst 4 [³⁵] 

2.3 Catalyst characterization

The precursors and the synthesized catalyst were characterized by infrared spectroscopy in the region of 450 cm^-1 to 4000 cm^-1 and UV-Vis spectra were recorded in the range 200-700 nm.

2.4 Catalytic test

The enantioselective epoxidation of styrene using in situ generated dimethyldioxirane (DMD) as the oxidizing agent and dimeric homochiral Mn(III)-Schiff base was carried out varying olefin/oxidant molar ration, catalyst loading, reaction temperature and presence of nitrogen coordinating co-catalysts. The initial reaction conditions were 0.17 mmol KHSO₅ in 8 ml of water, 0.17 mmol styrene, 1 mol% catalyst, 17 °C, absence of co-catalyst and 15 min of reaction time. For all reactions, two solutions were used. Firstly, a buffer solution (aqueous NaHCO₃, 5% w/w), for keeping the pH in a range of 7.8-8.3 values. This is because the pH control during the catalytic tests is important since the formation of DMD by reaction between acetone and KHSO₅ takes place in a slightly basic pH range. The second solution was the amount required of KHSO₅ in form of Oxone^® (2KHSO₅•KHSO₄•K₂SO₄) dissolved in 8 ml of distilled water. The reaction time was determined by the time of addition of the second solution (approximately 15 min), time in which the reaction was stopped. Subsequently, the reaction mixture was centrifuged in order to remove the catalyst containing solid. To the free solid liquid phase, 5 mL of dichloromethane were added obtaining two phases: aqueous and organic (reaction products). The aqueous phase was discarded off. The organic phase was concentrated and dried with anhydrous Na₂SO₄. The reaction products were analyzed by gas chromatography (GC) with flame ionization detector (FID) and using toluene (15 µl) as internal standard. The conditions of the method used were helium as mobile phase at 33 psi, split ratio = 100:1, injector and flame ionization detector temperature at 280 °C, heating program: 50 °C for 1 min, from 50 °C to 80 °C at heating rate of 2 °C/min, 80 °C for 2 min, from 80 °C to 200 °C at heating rate of 10 °C/min, 200 °C for 12 min.

3.1 Catalyst characterization

In Figure 2, the infrared spectrum of the dialdehyde ligand evidences the “bridge”, in form of methylene, that connects the two aromatic rings by the presence of the peak between 760 and 650 cm^-1 and its overtone in 1740 (dotted black line) [³⁸]. This signal remains present in the spectrum of the dimeric ligand and the dimeric catalyst. Both the Shiff base and the dimeric ligand Schiff base show a band (dotted red line) around 1630 cm^-1, which is associated with the vibrations of the imine group (C=N) [⁸].

Figure 2 FT-IR spectra of (1) Dialdehyde Ligand, (2) Schiff Base, (3) Dimeric Ligand Schiff Base, (4) Dimeric Catalyst, (5) Monomeric Catalyst. *bands corresponding to the structural changes generated by the complexation of the metal 

This band in the catalyst dimeric is displaced towards 1610 cm^-1 (dotted blue line) evidencing the complexation of Mn by dimeric salen ligand. Furthermore, the bands located at 485, 570 and 1535 cm^-1 corresponding to the bonds Mn-N, Mn-O and C-O are related with the complexation of the manganese atom [⁸]. On the other hand, it is observed that the dimerization of the Jacobsen catalyst does not generate additional vibrational effects besides the band corresponding to the “bridge” between the two aromatic rings, in comparison to commercial monomeric catalyst, which confirms the success of the synthesis [³⁹].

In Figure 3, the three ligands show bands that are close to 230 nm corresponding to transitions σ→σ*, close to 262 nm that are attributed to transitions π→π * and about 334 nm belonging to electronic transitions n→π * [⁸]. In the case of the dimeric catalyst two additional bands were observed, the first of them at 436 nm corresponding to metal-ligand charge transfers due to the complexation of the manganese atom, and the second of them at 510 nm attributed to electronic transitions d → d in the metal atomic orbitals [⁴⁰]. As in the infrared spectra, in the ultraviolet spectra is observed that in comparison with the monomeric catalyst, the dimerization does not generate additional electronic transitions [³⁹].

Figure 3 UV-vis spectra of (1) Dialdehyde Ligand, (2) Schiff Base, (3) Dimeric Ligand Schiff Base, (4) Dimeric Catalyst, (5) Monomeric Catalyst. *bands corresponding to electronic transits given by the complexation of the metal 

3.2 Catalytic activity

The dimeric homochiral Mn(III)-Schiff base complex catalyst was evaluated in the enantioselective epoxidation of styrene using in situ generated DMD. A scheme of this reaction is outlined in Figure 4.

Figure 4 Enantioselective epoxidation reaction of styrene using DMD generated in situ and catalyst 4 

The enantiomeric excess is determined from chromatographic areas of the 2 enantiomers (styrene oxides) by using the following Equation (1):

In this case, the majority enantiomer is the styrene R-oxide. In gas chromatography, the detector response (areas under the curve) is proportional to the amount of analyte in the volume thereof, that is, to the concentration of the analyte. Therefore, concentrations are replaced by areas and this Equation (2) is used.

The conversion increases as the styrene/KHSO₅ molar ratio increases [Figure 5]. Because the oxidant dissociates and forms dimethyldioxirane when it comes in contact with acetone, there is a non-catalytic oxidation for those molecules distanced from the sterogenic center of the catalyst. For this reason, the increment in conversion is higher than the enantiomeric excess of the product.

The increase in the enantiomeric excess of the product by increasing the catalyst loading is due to the decrease in the non-catalytic oxidation route of styrene [Figure 6]. The latter is due to a higher number of molecules of catalyst in the reaction, which allows a greater interaction between the incoming substrate and the catalytically active center. On the other hand, it is observed that the increase of the catalyst loading, from 2 to 5 mol%, does not have any considerable effect on the enantiomeric excess of the products.

Figure 5 Effect of the styrene/KHSO₅ molar ration in the enantioselective epoxidation of styrene. Reaction conditions: 8 ml acetone, 0.17 mmol styrene, 1 mol% catalyst, 8 ml water with amount of KHSO₅ corresponding (dependent of styrene/KHSO₅ molar ration), reaction time of 15 min and temperature of 17 °C 

Figure 6 Effect of catalyst loading in the enantioselective epoxidation of styrene. Reaction conditions: 8 ml acetone, 0.17 mmol styrene, 8 ml water with 1.36 mmol KHSO₅, 15 min and 17 °C 

As it is shown in Table 1, the presence of NMO or PyNO does not affect remarkably the catalytic activity. These compounds are used as oxygen transfer agents applied to the oxidant source from the aqueous phase to the organic phase. In this case, the oxidant is generated in the reaction medium (acetone-water homogeneous mixture), and therefore it is not expected to have any beneficial effect on the reaction.

Table 1 Effect of the presence of a co-catalyst in the enantioselective epoxidation of styrene* 

*Reaction conditions: 8 ml acetone, 0.17 mmol styrene, 2 mol% catalyst, 8 ml water with 1.36 mmol KHSO5, 15 min and 17°C.

At decreasing temperature, low conversions were obtained [Figure 7] due to decreasing kinetics energy. A constant amount of oxidant and low reaction kinetics result in an increment of non-catalytic epoxidation by the dissociation of KHSO₅. It is well-known that in this reaction, the key point is the stereo-electronics interactions between the incoming substrate and catalytically active center [⁴¹]. At elevated temperatures (25°C), this type of interactions is not effective due to the increase of the reaction rate, resulting in total conversions of the substrate, but low enantiomeric excess of epoxides.

Figure 7 Effect of reaction temperature in the enantioselective epoxidation of styrene. Reaction conditions: 8 ml acetone, 0.17 mmol styrene, 2 mol% catalyst, 8 ml water with 1.36 mmol KHSO₅, absence of co-catalyst and a reaction time of 15 min 

Table 2 Effect of separation method in catalyst recovery 

Table 2 shows that (1) regardless of the catalyst used (monomeric or dimeric) centrifugation is the best method of catalyst separation, this is because that the catalyst remains visibly evident in the filter paper used, (2) the dimeric catalyst is easier to recover than the monomeric catalyst due to the decrease of its solubility which in turn is given by molecular weight increase. Also, as expected, there is not a difference in reaction results.

Table 3 Reusability of dimeric catalyst using centrifugation as catalyst recovery method 

The Table 3 shows that in the catalyst reusability experiments there is a loss in the enantiomeric excess of the epoxides. The previous was attributed to physical losses of the catalyst during the separation process since the infrared spectrums of the reused catalyst do not reveal any type of oxidative degradation (see Figure 8]. However, since the amount of catalyst recovered each time is less, there is a decrease in the intensity of signals in the spectrum.

It was found that in absence of catalyst, a similar conversion than the catalyzed reaction was reached. However, the enantiomeric excess decreases significantly (3 % e.e.) because there is no sterogenic center (catalyst) "directing" the reaction towards a single enantiomer. On the other hand, no reaction was observed in absence of KHSO₅.

Figure 8 FT-IR spectra of (a) Dimeric Catalyst fresh, (b) first reuse, (c) Second reuse, (d) Third reuse