Preparation of new layered double hydroxides exchanged with osmate for asymmetric dihydroxylation of olefins to vicinal diols

The present invention relates to preparation of layered double hydroxides exchanged with osmate (LDH-osmates) useful as recyclable catalysts for preparing vicinal diols. More particularly the present invention relates to preparation of layered double hydroxides exchanged with osmate of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation (Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ or Ca 2+ ); M III is a trivalent ion (Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ , Co 3+ or Ni 3+ ), x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4; and methods of preparation and use thereof. The LDH-osmates of this invention are recyclable catalysts for preparing vicinal diols by asymmetric dihydroxylation (AD) of olefins in presence of cinchona alkaloid compounds.

This invention particularly relates to an eco-friendly process employing recyclable LDH-osmates as heterogeneous catalysts in place of soluble osmium catalysts for preparing vicinal diols by asymmetric dihydroxylation of olefins in presence of cinchona alkaloid compounds. The dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals. For example the products of cinnamic acid esters are intermediates for taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antiboitic. Propranolol, a β blocker can also be derived from the diol obtained through this method.

There are serious disadvantages in performing the catalytic AD reaction with homogeneous system in the manufacture of vicinal diols due to presence of toxic remnants of osmium in products and high cost of osmium tetroxide or potassium osmate dihydrate. By employing the heterogeneous catalytic system, the cost naturally comes down due to easy recovery and recyclability of the catalyst for number of recycles and very insignificant loss of osmium tetroxide, when compared with homogenous system. The products thus obtained using heterogeneous catalyst system are benign in the sense that the presence of osmium in minor impurities in the dihydroxylated products is also precluded.

Reference is made to U.S. Pat. Nos. 4,871,855 and 5,260,421 wherein asymmetric dihydroxylation of olefins are carried by osmium tetroxide and cinchona alkaloids in homogeneous way. The inherent disadvantages in this process are cumbersome procedure for the recovery of the osmium catalyst from the reaction mixture, generation of toxic waste and possibility of presence of toxic osmium in traces in the product.

Reference is made to U.S. Pat. No. 5,516,929 wherein asymmetric dihydroxylation of olefins are carried by osmium tetroxide and polymer-bound cinchona alkaloids in heterogeneous way. The drawbacks are difficulty in quantitative recovery of toxic osmium catalyst, lower enantioselectivity and reduction in activity and enantioselectivity in each and every recycle experiments.

Reference is made to U.S. Pat. No. 5,968,867 wherein asymmetric dihydroxylation of olefins are carried by osmium tetroxide and silicagel supported bis-cinchona alkaloid derivatives in heterogeneous way. The drawbacks are difficulty in quantitative recovery of toxic osmium catalyst and reduction in activity and enantioselectivity in each and every recycle experiments.

Reference is made to European patent EP 940,170 A2 wherein catalytic asymmetric dihydrpxylation of alkenes are carried by using a polymer-supported osmium tetroxide catalyst. The drawbacks are requiring higher amount of catalyst (5 mol %/), longer reaction time and use of expensive polymer as a support.

The main object of the present invention is to prepare a heterogeneous recyclable LDH-osmates and to use in catalytic amounts for preparing vicinol diols by asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds which obviates the drawbacks as detailed above.

Another object of the present invention is LDH as synthesized having interstitial anions such as chloride, nitrate, carbonate, sulfate or calcination of LDH having the said interstitial anions at temperatures in the range of 350 to 550° C. are used as precursors for the preparation of LDH-osmates.

Still another object of the present invention is to recover the heterogeneous LDH-osmates used in asymmetric dihdroxylation by simple filtration and reuse for number of cycles with consistent activity and enantioselectivity.

Still another object of the present invention is the quantity of LDH-osmate used in the reaction is 0.01 to 3 mol % of osmium with respect to the substrate.

Still another object of the present invention is wherein the co-oxidant is N-methylmorpholine N-oxide (NMO), trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate or molecular oxygen.

Still another object of the present invention is the chiral ligand is monomeric or polymeric, preferably hydroquinidine 1,4-phthalazinediyl diether (DHQD) 2 PHAL), hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQD) 2 PYR), hydroquinidine (anthraquinone-1,4-diyl) diether ((DHQD) 2 AQN), hydroquinidine acetate (DHQD-OAc), O-(4-chlorobenzoyl) hydroquinidine (DHQD-CLB), hydroquinidine 9-phenanthryl ether (DHQD-PHN), hydroquinidine 4-methyl-2-quinolyl ether (DHQD-MEQ) or the other pseudoenantiomeric forms of these ligands, etc.

Accordingly, the present invention relates to a LDH-osmate useful as a catalyst having the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ and M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ , x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4.

In another embodiment, the present invention relates to a process for the preparation of the catalyst LDH-osmate of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ]x/2 .zH 2 O wherein z is the number of water molecules, the said process comprising reacting potassium osmate of formula K 2 OsO 4 2H 2 O with a LDH of formula [M II (1−x) M III x (OH) 2 ][A n− ] x/n .zH 2 O where M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ and M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ , x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, in an aqueous solvent at a temperature ranging between 20 to 30° C. for a period of 5 to 24 h under the nitrogen atmosphere followed by filtration to obtain the desired catalyst.

In yet another embodiment, the present invention relates to a method for the preparation of vicinal diols using the recyclable catalyst LDH-osmates of the formula [M II (l−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation (Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ or Ca 2+ ); M III is a trivalent ion (Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ or Co 3+ ), x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, in catalytic amounts by asymmetric dihydroxylation of olefins using standard methods employing an oxidant in the presence of a cinchona alkaloid compound in a solvent selected from water, acetone, acetonitrile, t-butanol or any mixture thereof at a temperature in the range of −20 to +100° C. for a period 0.5 to 24 h, and obtaining the pure product vicinol diol by a conventional method.

In an embodiment of the present invention, a method for the preparation of vicinol diols using the recyclable catalyst LDH-osmates of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ ; M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ , x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, in catalytic amounts by dihydroxylation of olefins using standard methods employing an oxidant in a solvent selected from water, acetone, acetonitrile, t-butanol or any mixture thereof at a temperature in the range of −20 to +100° C. for a period 0.5 to 24 h, and obtaining the pure product vicinal diol by conventional method.

In an embodiment of the present invention, the catalyst has an osmium content in the range between 5 to 30%.

In an embodiment of the present invention, LDH as synthesized has interstitial anions such as chloride, nitrate, carbonate, sulfate.

In a further embodiment of the present invention LDH having the said interstitial anions calcined at temperatures in the range of 350 to 550° C. are used as precursors for the preparation of LDH-osmates.

In an embodiment of the present invention, the quantity of LDH-osmate used in the reaction is 0.01 to 3 mol % of osmium content with respect to the substrate.

In an embodiment of the present invention, LDH-osmate is recovered by simple filtration and reused for several cycles with consistent activity.

In another embodiment of the present invention, the solvent selected for the AD reaction is water, acetone, acetonitrile and/or t-butanol, etc.

In yet another embodiment of the present invention, the oxidant used is selected from the known group consisting of N-methylmorpholine N-oxide (NMO), Trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate or molecular oxygen.

In still another embodiment of the present invention, the chiral ligand used is selected from the known group consisting of the monomeric or polymeric, preferably (DHQD) 2 PHAL, (DHQD) 2 PYR, (DHQD) 2 AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ or the other pseudoenantiomeric forms of these ligands, etc.

In still another embodiment of the present invention, the reaction is, preferably, effected at a known temperature, in the range of −20 to +100° C. for a period of 0.5 to 24 h.

In still another embodiment of the present invention, the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals. Products selected from taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antibiotic.

The novelty of the present invention lies in the design and preparation of LDH-osmates through simple exchange process for the first time and uses it in catalytic amounts for preparing vicinal diols by asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds. Higher yields and enantioselectivities are obtained when LDH-osmate catalysts are used in the asymmetric dihydroxylation of olefins in aqueous organic solvents. Since the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals, this invention which envisages reduction of toxic osmium metal content in these products is timely and appropriate, due to use of heterogeneous catalyst. The consistent activity and enantioselectivity obtained for several cycles in asymmetric dihydroxylation makes the process economical and possible for commercial realisation. Therefore, LDH-osmates are better option for the synthesis of vicinal diols. The use of different metals and in varied compositions used in the preparation of LDH support has no impact on its final form of osmate catalysts with respect to activity and enantioselectivity. Thus this invention offers the best techno-economic route for the synthesis of vicinal diols, intermediates for the preparation of drugs and pharmaceuticals.

LDH-osmate having the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ and M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ , x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, is useful as a catalyst in the process. The catalyst LDH-osmate of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O is prepared by reacting potassium osmate of formula K 2 OsO 4 2H 2 O with a LDH of formula [M II (1−x) M III x (OH) 2 ][A n− ] x/n .zH 2 O wherein M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ and M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ , x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, in an aqueous solvent at a temperature ranging between 20 to 30° C. for a period of 5 to 24 h under the nitrogen atmosphere followed by filtration to obtain the desired catalyst.

The vicinal diols are prepared using the recyclable catalyst LDH-osmates of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation (Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ ); M III is a trivalent ion (Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ or Co + ), x is the mole fraction having integral value ranging from 0.2 to 0.33, and z is the number of water molecules and ranges from 1 to 4, in catalytic amounts by asymmetric dihydroxylation of olefins using standard methods employing an oxidant in the presence of a cinchona alkaloid compound in a solvent selected from water, acetone, acetonitrile and/or t-butanol at a temperature in the range of −20 to +100° C. for a period 0.5 to 24 h, and obtaining the pure product vicinol diol by a conventional method.

The preparation of vicinol diols may also be done using the recyclable catalyst LDH-osmates of the formula [M II (1−x) M III x (OH) 2 ][OsO 4 2− ] x/2 .zH 2 O wherein M II is a divalent cation selected from the group consisting of Mg 2+ , Mn 2+ , Fe 2+ , Co 2+ , Ni 2+ , Cu 2+ , Zn 2+ and Ca 2+ ; M III is a trivalent ion selected from the group consisting of Al 3+ , Cr 3+ , Mn 3+ , Fe 3+ and Co 3+ in catalytic amounts by dihydroxylation of olefins using standard methods employing an oxidant in a solvent selected from water, acetone, acetonitrile and/or t-butanol at a temperature in the range of −20 to +100° C. for a period 0.5 to 24 h, and obtaining the pure product vicinal diol by conventional method.

The osmium content in the catalyst ranges between 5 to 30%. LDH as synthesized has interstitial anions such as chloride, nitrate, carbonate, sulfate. Calcined LDH having the said interstitial anions at temperatures in the range of 350 to 550° C. may also be used as precursors for the preparation of LDH-osmates. Generally, the quantity of LDH-osmate used in the reaction is 0.01 to 10 mol % of osmium content with respect to the substrate. LDH-osmate is recovered by simple filtration and reused for several cycles with consistent activity.

The solvent selected for the AD reaction is selected from the group consisting of water, acetone, acetonitrile, t-butanol, or any mixture thereof The oxidant used is selected from the group consisting of N-methylmorpholine N-oxide (NMO), Trimethylamine N-oxide, hydrogen peroxide, t-butyl hydrogen peroxide, potassium ferricyanide, sodium periodate or molecular oxygen.

The chiral ligand used is selected from the group consisting of the monomeric or polymeric, preferably (DHQD) 2 PHAL, (DHQD) 2 PYR, (DHQD) 2 AQN, DHQD-OAc, DHQD-CLB, DHQD-PHN, DHQD-MEQ or the other pseudoenantiomeric forms of these ligands. The reaction is, preferably, effected at a known temperature, in the range of −20 to +100° C. for a period of 0.5 to 24 h. The dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals. Products selected from taxol side chain, an anticancer drug, diltiazem, calcium antagonist and chloramphenicol, an antibiotic.

Scientific Explanation

In the present invention, LDH-osmates are prepared for the first time and used in catalytic amounts for preparing vicinal diols by asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds in a heterogeneous way.

LDH-osmates are prepared by anion exchange method from the LDH containing chloride or nitrate anions. The osmate anions in LDH are responsible for the dihydroxylation activity of the reaction. The activity of LDH-osmate is similar or higher than the homogeneous counter parts. The higher activity is ascribed to the support effect. The large positive electric potential of OsO 4 2− LDH surface induces polarization of N→O bond and facilitates oxygen transfer.

Higher yields and enantioselectivities are obtained with LDH-osmate catalysts used in the asymmetric dihydroxylation of olefins in aqueous organic solvents. Since the dihydroxylated products are important intermediates for the preparation of drugs and pharmaceuticals, this invention is timely and appropriate. Therefore, LDH-osmate is a better option for the synthesis of vicinal diols. The LDH-osmate catalysts prepared irrespective of metals used in the preparation of LDH offered good yields and enantioselectivies in presence of cinchona alkaloids. Thus this invention offers the best techno-economic route for the synthesis of vicinal diols, intermediates for the preparation of drugs and pharmaceuticals.

LDH-osmates are prepared as examplified and used in catalytic amounts for preparing vicinal diols by asymmetric dihydroxylation of olefins employing oxidants in presence of cinchona alkaloid compounds in a heterogeneous way as described in the examples.

The following examples are given by way of illustration of the present invention and therefore should not be construed to limit the scope of the invention.

Preparation of Layered Double Hydroxides