IMPROVED SYNTHESIS OF AN EXPOXIDATION-CATALYST

Abstract

The present invention relates to an improved process to produce a specific and very efficient epoxidation-catalyst (1,2:4,5-Di-O-isopropylidene-β-D-erythro-2,3-hexodiulo-2,6-pyranose).

Claims

1. Process to produce compounds of formula (I) ##STR00006## wherein in a first step (step (i) the compound of formula (II), ##STR00007## is reacted with a compound of formula (IV) ##STR00008## wherein R.sub.1 is H or a C.sub.1-C.sub.3 alkyl group (preferably —H, —CH.sub.3 or —CH.sub.2CH.sub.3), and R.sub.2 is a C.sub.1-C.sub.3 alkyl group (preferably —CH.sub.3 or —CH.sub.2CH.sub.3), and R.sub.3 is H or a C.sub.1-C.sub.2 alkyl group (preferably —H or —CH.sub.3), wherein R is a C.sub.1-C.sub.3 alkyl group in the presence of a solid acid catalyst and wherein the reaction product of step (ii), which is the compound of formula (III) ##STR00009## wherein R.sub.1 is the same as defined for the compound of formula (IV), is oxidized to a compound of formula (I).

2. Process according to claim 1, wherein the reaction of step (i) is carried out in the presence of at least one solvent. (preferably in at least one polar solvent).

3. Process according to claim 1, wherein the reaction of step (i) is carried out at temperatures between −5° C.-10° C.

4. Process according to claim 1, wherein the solid acid catalyst are functionalized ion-exchange resins.

5. Process according to claim 1, wherein the amount of the catalyst in step (i) is between 0.05-0.5 mol-eq (in view of D-fructose).

6. Process according to claim 1, wherein the reaction of step (ii) is carried out in at least one solvent (preferably in at least one polar aprotic solvent).

7. Process according to claim 1, wherein the reaction of step (ii) is usually carried out in presence of at least one transition metal catalyst (preferably a ruthenium metal catalyst).

8. Process according to claim 1, wherein compound of formula (IV) R.sub.1 is H, and R.sub.2 is —CH.sub.3, and R.sub.3 is —CH.sub.3.

9. Process according to claim 1, wherein compound of formula (IV) R.sub.1 is —CH.sub.2CH.sub.3, and R.sub.2 is —CH.sub.3, and R.sub.3 is H.

10. Compound of formula (Ia) ##STR00010##

Description

EXAMPLES

Example 1: Synthesis of Compound of Formula (III) (Step(i))

[0044] In a 200 ml flask 125 mMol D(−)fructose, 80 ml acetone and 0.2 eq Amberlyst 15 were stirred and cooled to 0° C.

[0045] Afterwards 280 mMol (2.236 eq) 2-methoxyprop-1-ene were solved in 40 ml acetone, transferred to a dropping funnel and added dropwise over 20 minutes to the reaction mixture at the same temperature (0° C.).

[0046] The temperature was maintained at 0-2° C. for 20 h.

[0047] After that, all fructose was reacted. Amberlyst 15 was filtered off. The pH was then adjusted to >7 (around pH 10) with 44% NaOHaq. The acetone was removed under vacuum on a rotary evaporator at 40° C. 25 ml Toluene were added and removed on the rotary evaporator to aid in the removal of the remaining traces of acetone. The residue (white slurry) was then dissolved in 100 ml toluene and washed with 30 ml saturated NaClaq and then 6 ml water. Aqueous phases one time extracted with toluene. Approximately half of the toluene was removed by vacuum on the rotary evaporator. 125 ml n-Heptane were added slowly to the warm solution. The resultant slurry was slowly cooled to <5° C. and filtered off.

[0048] The crude product (compound of formula (III) was washed with cold n-heptane and dried at 50° C. for 12 hours at 10-15 mbar to give 15.2 g of a product with a purity of 100% (GC area %), 58.4 mMol, yield 46.7%. The concentrated mother liquor contains further 17.2% (GC area %) of the product, yield 6.3%.

Example 1: Synthesis of Compound of Formula (I) (Step(ii))

[0049] In a 100 ml flask 5.21 g (20 mMol) Bis-acetonide (compound of formula (III) obtained) was dissolved in 26 ml diethoxymethane. To this solution, 65 mg tetrabutylammonium bromide (99.9%, 0.01 eq, 0.20 mMol), 0.637 g K.sub.2CO.sub.3 (99.8%, 0.23 eq, 4.6 mMol), and 0.135 g RuCl3.H2O (0.03 eq, 0.60 mMol) were added.

[0050] A solution of 6.38 g NaIO4 (99.2%, 1.48 eq, 29.6 mMol) in 44 g water was prepared and added to the alcohol slowly, keeping the temperature below 40° C. by external cooling with an ice bath. After 1 hour at room temperature the reaction was completed. 1.3 ml (0.84 eq, 16.85 mMol) 2-propanol was added. The mixture was stirred for 30 minutes, followed by a filtration over dicalite and washed with ethyl acetate. The clear phases were separated after extraction. Aqueous phase one time extracted with ethyl acetate. The organic extracts were washed with Na2SO3aq 10% solution followed by NaClaq 10%. The ethyl acetate was removed on a rotary evaporator and the residue (5.34 g) was dissolved in ˜40 ml heptane under heating. The solution was slowly cooled to room temperature until a slurry was formed. It was then cooled to 0° C., and the ketone was isolated by filtration. The wet cake was washed with cold heptane and dried in a vacuum oven at 50° C. and 10-15 mbar.

[0051] 4.51 g of white crystals of the compound of formula (I) with a purity of 94% by GC area % (82% yield) were obtained. The mother liquor was concentrated and a further 0.4 g. The residue is of the same quality=7.3% yield.