Silesian University of Technology, Department of Chemical Organic Technology and Petrochemistry, ul. Krzywoustego 4, 44-100 Gliwice, Poland
Agnieszka Drożdż, Anna Chrobok , K. Szymańska, J. Mrowiec-Białoń, A.B. Jarzębski
Literature:
[1] S. C. Lemoult, P. F. Richardson and S. M. Roberts, J. Chem. Soc., Perkin Trans. 1 (1995) 89.
[2] B. K. Pchelka, M. Gelo-Pujic, E. Guibé-Jampel, J. Chem. Soc., Perkin Trans. 1 (1998) 2625.
[3] M. Y. Rios, E. Salazar, H. F. Olivo, Green Chem. 9 (2007) 459.
[4] M. Y. Rios, E. Salazar, H. F. Olivo, J. Mol. Catal. B 54 (2008) 61.
[5] A. J. Kotlewska, F. van Rantwijk, R. A. Sheldon, I. W. C. E. Arends, Green Chem. 13 (2011) 2154.
Acknowledgement:
This work was financially supported by the Polish State Committee for Scientific Research (Grant no N N209 021739).
The study on the application of Candida Antarctica lipase B in the chemo-enzymatic Baeyer –Villiger oxidation of cyclic
ketones to lactones
0 25 50 75 100
0 10 20 30 40 50
Time [h]
10 mg MH-Hd-L
Yield of lactone [%]
30 mg MH-Hd-L 7.5mg MH-Hd-L 5 mg MH-Hd-L
10 mg Novozyme 0.5 g native lipase
0 25 50 75 100
0 5 10 15 20 25 30
Yield of lactone [%]
25oC 40oC 70oC
30 mg MH-Hd-L 10 mg MH-Hd-L 7.5 mg MH-Hd-L 5 mg MH-Hd-L
10 mg Novozyme 0.5 g native lipse
25ºC 40ºC 70ºC
Fig. 3. The values of apparent rate constant kobs of BVO of 2-methylcyclo- hexanone (0.5 mmol) with UHP (1 mmol) in ethyl acetate (1.5 mL) at RT using MH (black) and SBA-15 (grey) biocatalysts in amounts calculated to give 0.4 mg of lipase input.
Fig. 4. The effect of MH-Me-L (50 mg) reuse on rate constant (kobs– grey) and yield (black) of BV oxidation of 2-methylcyclohexanone (2.5 mmol) with 60% aq. H2O2(5 mol) in ethyl acetate (7.5 mL) at RT.
Entry Ketone Lactone Time (h)
Yielda (%)
1
O
CH3
O O
CH3
29 97
2
CH3 O
O O
C H3
74 82
3
O
O O
75 80
4
O
O O
6 92
5
O
O
O
8 94
6
O
O O
2 98
7
O
O O
6 35
b8
O
O O
96 7
cScheme 1. Chemo-enzymatic Baeyer–Villiger oxidation of 2-methylcyclohexanone.
Fig. 1. The influence of MH-Hd-L, Novozyme-435 and native lipase amount on the 2-methylcyclohexanone (0.5 mmol) oxidation with UHP (1 mmol) in ethyl acetate (1.5 ml)at RT.
Fig. 2. The influence of temperature on the 2-methyl- cyclohexanone (0.5mmol) oxidation with UHP (1mmol) and 10 mg of MH-Hd-L catalyst in ethyl acetate (1.5ml).
Table 2. Oxidation of selected cyclic ketones (1 mmol) to lactones with UHP (2 mmol) in the presence of 20 mg of MH-Me-L in ethyl acetate (3 mL) at RT.
a Isolated yields after column chromatography.
b MR analysis of post-reaction mixture confirmed the formation of corresponding hydroxyacid which was formed from lactone hydrolysis reaction.
c Yield determined by GC.
INTRODUCTION
The Baeyer-Villiger (BV) reaction is based on the formation of esters and lactones by the oxidation of ketones with peroxide derivatives. It is still one of the most important reactions in organic chemistry, with a large range of possible applications, including the synthesis of antibiotics, steroids, pheromones, and monomers for polymerization. The organic percarboxylic acids typically used as oxidants in these reactions are fairly expensive, often poorly stable and hazardous, and this consequently limits their commercial application. Therefore, the chemo-enzymatic approach appears to be a very attractive alternative. It involves oxidation of long- or medium-chain carboxylic acids with H2O2 or urea hydrogen peroxide (UHP) to generate in situ peracid which is later used to oxidise ketones to lactones. The former reaction can effectively be catalysed by lipases, and Candida Antarctica lipase B immobilised on acrylic resin (commercially available as Novozyme-435), owing to its excellent stability in organic solvents, has been frequently utilised for this purpose with a considerable success.
The aim of this work was to develop the new chemo-enzymatic method of lactone synthesis involved immobilised lipase as the biocatalyst of peracid formation, urea hydrogen peroxide (UHP) as oxidant and ethyl acetate as both the peracid precursor and solvent (Scheme 1). Making use of UHP and a heterogeneous biocatalyst we aimed to develop a clean BVO process with a facile catalyst separation and reuse. Investigation of the biocatalysts performance: activity, stability and reusability in BVO of cyclic ketones was studied.
RESULTS
Biocatalysts were obtained by immobilization of Candida Antarctica lipase B onto siliceous materials with multimodal pore structure (MH) and also on typical SBA-15, chemically modified with organosilanes terminated with methyl (Me), octyl (Oc) and hexadecyl (Hd) group.
Good stability of the biocatalysts was observed in at least 5 repeated catalytic cycles.
CONCLUSION
In summary, the developed biocatalysts show: very high activity, good stability and reusability demonstrated in the chemo- enzymatic Baeyer–Villiger oxidation of various cyclic ketons to the corresponding lactones.
Specific activity of biocatalysts functionalised with different groups decreased in the order Me > Oc > Hd.
Activities of all MH biocatalysts were also significantly larger than that of the corresponding biocatalysts fabricated using mesoporous silica of SBA-15 type.
The rate constant in oxidation of 2- methylcyclohexanone with UHP was three times higher for the best catalyst (MH-Hd-L), than for Novozyme-435, which is the most common lipase biocatalyst in peroxidation reactions.
L. p. Biocatalyst
Contents of lipase a
[mg/g]
1 MH-Hd-L 198
2 MH-Oc-L 116
3 MH-Me-L 80
4 SBA-Hd-L 142
5 SBA-Oc-L 99
6 SBA-Me-L 75
a determined by thermogravimetric analysis
Table 1. New biocatalysts
