Title of Invention	"A PROCESS FOR THE PREPARATION OF VICINAL DIOL WSING THE RECYCLABLE CATALYST LDH-OSMATE"
Abstract	A process for the preparation of vicinal diol using the recyclable catalyst LDH- Osmate A process for the preparation of vicinal diol using the recyclable catalyst LDH- osmate by dehydroxylating the olefin by using standard method with recyclable catalyst LDH-osmate in an amount in the range of 0.01 to 3 mol% in the presence of an oxidant in a solvent at a temperature in the range of -20 to 100°C for a period 0.5 to 24 h, to obtain the pure product vicinal diol by conventional method, if desired carrying out the above reaction in presence of a cinchona alkaloid compound to obtain the pure product chiral vicinal diol.

Title of Invention

"A PROCESS FOR THE PREPARATION OF VICINAL DIOL WSING THE RECYCLABLE CATALYST LDH-OSMATE"

Abstract

A process for the preparation of vicinal diol using the recyclable catalyst LDH- Osmate A process for the preparation of vicinal diol using the recyclable catalyst LDH- osmate by dehydroxylating the olefin by using standard method with recyclable catalyst LDH-osmate in an amount in the range of 0.01 to 3 mol% in the presence of an oxidant in a solvent at a temperature in the range of -20 to 100°C for a period 0.5 to 24 h, to obtain the pure product vicinal diol by conventional method, if desired carrying out the above reaction in presence of a cinchona alkaloid compound to obtain the pure product chiral vicinal diol.

Full Text	The present invention relates to a process for the preparation of vicinal diols using the recyclable catalyst LDH-osmate. More particularly the present invention relates to a process for the preparation of vicinol diol by asymmetric dihydroxylation (AD) of an olefin using the recyclable catalyst LDH-osmates of the formula [M11(i.X) M111x (OH)2][OsO42' ]x/2.zH2O wherein M" is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Mi2"1", Cu2+, Zn2+ and Ca2+; M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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. The catalyst LDH-osmate of the formula [MII(i.X)MIIIx(OH)2][OsO42"]x/2.zH2O wherein z is the number of water molecules is prepared as described and claimed in our co-pending application no. NF 327/00. 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 ft 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 US patents US 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 US patent US 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 US patent US 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 dihydroxylation 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 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)2PHAL), hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQD)2PYR), hydroquinidine (anthraquinone-1,4-diyl) diether ((DHQD)2AQN), 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. Accordingly, the present invention relates to a process for the preparation of vicinal diol using the recyclable catalyst LDH-osmate which comprises dehydroxylating the olefin by using standard method with recyclable catalyst LDH-osmate in an amount in the range of 0.01 to 3 mol% in the presence of an oxidant such as herein described in a solvent at a temperature in the range of -20 to 100°C for a period 0.5 to 24 h, to obtain the pure product vicinal diol by conventional method, if desired carrying out the above reaction in presence of a cinchona alkaloid compound to obtain the pure product chiral vicinal diol. 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 another embodiment of the present invention the LDH-osmate is recovered by simple filtration and reused for several cycles with consistent activity. In yet another embodiment the oxidant used is selected from the known group consisting of N-methylmorpholine N-oxide (NMO), Trimethylamine N-oxide, hydrogen peroxide, potassium ferricyanide, sodium periodate or molecular oxygen. A process as claimed in claims 1-4 wherein the cinchona alkaloid compound used is selected from the known group consisting of monomeric or polymeric, preferably hydroquinone 1,4-phthalazinediyl diether, hydroquinidine 2,5-diphenyl-4,6- pyrimidinediyl diether, hydroquinidine (anthraquinone-1,4-diyl) diether, hydroquinidine acetate, O-(4-chlorobenzoyl) hydroquinidine, hydroquinidine 9- phenanthryl ether, hydroquinidine 4-methyl-2-quinolyl ether and other pseudoenantiomeric forms of these ligands. In still another embodiment the solvent used is selected from the group consisting of water, acetone, acetonitrile, t-butanol and mixture thereof. 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 [MII(i.x)MIIIx (OH)2][OsO42"]x/2.zH2O wherein M" is a divalent cation selected from the group consisting of Mg2"1", Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+ and M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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"(i.x) Mmx (OH)2][OsO42~]x/2.zH2O is prepared by reacting potassium osmate of formula K2OsO4 2H2O with a LDH of formula [M"(i.X) M'"X (OH)2][An"]x/n.zH20 wherein M" is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+ and M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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 [Mn(i.x) Mmx (OH)2][OsO42"]x/2.zH2O wherein M11 is a divalent cation (Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+); M111 is a trivalent ion (A13+, Cr3+, Mn3+, Fe3* or Co3); 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 olefms 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 [MII(1.X)MIIIx(OH)2][OsO42"]x/2-zH2O wherein M11 is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+; M111 is a trivalent ion selected from the group consisting of Al3"1", Cr3+, Mn3+, Fe3+ and Co3+ in catalytic amounts by dihydroxylation of olefms 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)2PHAL, (DHQD)2PYR, (DHQD)2AQN, 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. 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 Example 1 Preparation ofMg2+/Al3+/Cr -LDH (la) A mixture of MgCl2.6H2O (30.49 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was dissolved in 200 mL of deionised water. The resultant aqueous solution was slowly added at 25°C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH of the reaction mixture was maintained constantly (-10) by the continuous addition of 2 M NaOH. The suspension thus obtained was stirred overnight under a nitrogen atmosphere at 70°C. The solid product was isolated by filtration, washed thoroughly with deionised water, and dried overnight at 80°C. Decarbonated water was used in all the synthetic steps. Mg2VAl3+/Cl~ hydrotalcites of the different Mg/Al ratios were also prepared similarly, using appropriate amounts of magnesium chloride hexahydrate and aluminium chloride hexahydrate. Example 2 Preparation of Mg2+/Al3+/NO3~ -LDH (Ib) The Mg2+/Al3+/NO3" hydrotalcite with a Mg/Al ratio of 3:1 was prepared from magnesium nitrate hexahydrate (30.8 g, 0.12 mol) and aluminum nitrate nonahydrate (15.0 g, 0.04 mol) which were dissolved in 100 ml of deionised and decarbonated water. The pH of the solution was adjusted to -10 by the addition of NaOH (2M). The slurry was stirred for 2 h at room temperature under nitrogen atmosphere and then filtered under nitrogen atmosphere, washed thoroughly and dried under vacuum at 80°C. Example 3 Preparation of MS2+/Al3+/CO32' -LDH (Ic) A mixture of 60.09 g of Mg(NO3)2.6H2O (0.234 mol) and 29.31 g of A1(NO3)3.9H2O (0.078 mol) in 70 ml distilled water was added to a solution of 28.12 g, 50% aq. NaOH (0.703 mol) and 22.08 g Na2CO3 (0.41 mol) in 100 ml distilled water. The addition was carried out slowly in a 500 ml flask equipped with a mechanical stirrer and the resultant heavy slurry was heated at 65 ± 5°C for about 18 h. The slurry was allowed to cool to room temperature, filtered and washed. The solid was then dried and calcined at 450°C for 6h in airflow. Example 4 Preparation of M2+/Al3+/Cr - LDH (Id) A mixture of NiCl2.6H2O (35.65 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was dissolved in 200 mL of deionised water. The aqueous solution was slowly added at 25 °C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH was constantly maintained (-10) by the continuous addition of 2 M NaOH. The suspension was stirred overnight under a nitrogen atmosphere at 70°C. The solid product was isolated by filtration, washed thoroughly with deionised water, and dried overnight at 80°C. All synthetic steps were carried out using decarbonated water. Preparation of LDH-osmates Example 5 Preparation of (MgAl)LDH-OsO42' (IIa) 1g of la was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product is filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 25.6 % of osmium. This means that 1.345 mmol of osmium per 1 gram of the product. The release of equivalent amounts of chloride ions were also quantitatively estimated by titration of the combined filtrates with 0. IN AgNO3 solution in presence of KCrO4 indicator. Example 6 Preparation of (MgAl)LDH-OsO42~ (II b) Ig of Ib was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 18.4 % of osmium. This means that 0.966 mmol of osmium per 1 gram of the product. Example 7 Preparation of (MgAl)LDH-OsO42' (IIe) Ig of calcined Ic was suspended in 100 ml of 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 19.95 % of osmium. This means that 1.048 mmol of osmium per 1 gram of the product. Example 8 Preparation of (NiAl)LDH-OsO42' (IId) Ig of Id was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25 °C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 24.2 % of osmium. This means that 1.271 mmol of osmium per 1 gram of the product. The release of equivalent amounts of chloride ions were also quantitatively estimated by titration of the combined filtrates with 0.1N AgNOa solution in presence of KCrO* indicator. Asymmetric Dihydroxylation of Olefins The asymmetric dihydroxylation reaction of olefins was performed using the following two methods in order to evaluate LDH-osmates of the present invention. Method I LDH-osmates of the formula IIa-IId (0.02 eq. wt. of osmium content in the LDH), cinchona alkaloid (DHQD)2PHAL (0.02 Eq. Wt.) and N-methylmorpholine-N-oxide (1.5 Eq. Wt.) were stirred for 30 min in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1). To this mixture was added an olefin (1.0 Eq. Wt). After the reaction, the LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The concentrated organic layer was purified to afford the corresponding cis-diol by using conventional processes. The yield and the optical purity of the product were determined. Method II LDH-osmate of the formula Ila-IId (0.002.about.0.02 Eq. Wt. of osmium content in the LDH), cinchona alkaloid (DHQD)2PHAL (0.02 Eq. Wt.),-.potassium ferricyanide (K3 Fe(CN)6, (3.0 Eq. Wt.) and potassium carbonate (K2 CO3, 3.0 Eq. Wt.) were stirred for 30 min in the mixed solvent of tert-butanol/water (in the volume ratio of 1:1). To this mixture was added an olefin (1.0 Eq. Wt). After the reaction, LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The concentrated organic layer was purified to afford the corresponding cis-diol by using conventional processes. The yield and the optical purity of the product were determined. Catalytic asymmetric dihydroxylation of olefins using N-methylmorpholine-N-oxide as a co-oxidant Example 9 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa LDH-osmate of the formula IIa (0.02 Eq. Wt.), Hydroquinidine 1,4-phthalazinediyl diether ((DHQD)2PHAL) (0.02 Eq. Wt.) and N-methylmorpholine-N-oxide (1.5 Eq. Wt.) were stirred for 30 min in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1). To this mixture was added trans-stilbene (1.0 Eq. Wt) and stirred at room temperature for 6 hours. After the reaction, LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The pure product was obtained by removing the solvent at reduced pressure followed by column chromatography. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%) [α]D +92.44 (c 1.0, EtOH): e.e.=99.4% Example 10 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 9 without further addition of osmate catalyst. The reaction was performed using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 95%) [oc]D +92.90 (c 1.0, EtOH): e.e.=99.9% Example 11 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 10 without further addition of LDH-osmate catalyst. »he reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 97%) [α]D+92.16 (c 1.0, EtOH): e.e.=99.1% Example 12 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 11 without further addition of LDH-osmate catalyst. The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 97.0% of enantiomeric excess was obtained (yield 94%) [α]D +90.76 (c 1.0, EtOH): e.e.=97.6% Example 13 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 12 without further addition of LDH-osmate catalyst. The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%) [α]D +92.81 (c 1.0, EtOH): e.e.=99.8% Example 14 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila which had been used in Example 13 without further addition of LDH-osmate catalyst. The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 98%) [α]D +92.25 (c 1.0, EtOH): e.e =99.2% Example 15 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by LDH-osmate of the formula IIb The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 97%) [α]D +92.34 (c 1.0, EtOH): e.e =99.3% Example 16 Catalytic asymmetric dihydroxylation reaction of trans-stilbene. by using LDH-osmate of the formula IIc The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 95%). [α]D +92.53 (c 1.0, EtOH): e.e.=99.5% Example 17 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IId The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%). [Α]D +92.25 (c 1.0, EtOH): e.e.=99.2% Example 18 Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9 except the cinchona alkaloid is DHQD-CLB. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 98.0% of enantiomeric excess was obtained (yield 92%) [α]D + 91.32 (c 1.0, EtOH): e.e.=98.2% Example 19 Catalytic asymmetric dihydroxylation reaction of styrene by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (R)-phenyl-1,2-ethanediol of more than 95.0% of enantiomeric excess was obtained (yield 94%) [α]D -34.29 (c 1.0, EtOH): e.e.=95.7% Example 20 Catalytic asymmetric dihydroxylation reaction of trans-beta.-methyl styrene by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (R,R)-l-phenyl-l,2-propanediol of more than 98.0% of enantiomeric excess was obtained (yield 97%) [α]D -30.50 (c 1.0, EtOH): e.e.=98.1% Example 21 Catalytic asymmetric dihydroxylation reaction of methyl trans-cinnamate by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (2S,3R)-2,3-dihydroxy-3-phenylpropionate of more than 97.0% of enantiomeric excess was obtained (yield 96%) [α]D -10.46 (c 1.0 , CHC13): e.e.=97.8% Example 22 Catalytic asymmetric dihydroxylation reaction of allyl 1-naphthyl ether by using LDH-osmate of the formula IIa The reaction was performed by using an identical process as in Example 9.1 except slow addition of olefin with a reaction time of 12 hours. 2,3-dihydroxypropyl-1-naphthyl ether of more than 77.0% of enantiomeric excess was obtained (yield 94%) [α]D +5.18 (c 1.0, CH3OH): e.e.=77.4% Example 23 Catalytic asymmetric dihydroxylation of olefins using potassium ferricyanide as a co-oxidant Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila LDH-osmate of the formula Ila (0.02 Eq. Wt.), bis-cinchona alkaloid of the formula (DHQD)2PHAL (0.02 Eq. Wt.), potassium ferricyanide (K3Fe(CN)6,3.0 Eq. Wt.) and potassium carbonate (K2CO3, 3.0 Eq. Wt.) were stirred for 30 min in the mixed solvent of tert-butanol/water (in the volume ratio of 1:1). To this mixture was added trans-stilbene (1.0 Eq. Wt). After a reaction time of 6 hours, LDH-osmate catalyst separated by filtration. After washing with methanol, combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The pure product was obtained by removing the solvent at reduced pressure followed by column chromatography. (S,S)-(-)-l,2-diphenyl-l,2-ethanediol of more than 99.0% of enantiomeric excess was obtained (yield 95%). [α]D +92.90 (c 1.0, EtOH): e.e.=99.9% Example 24 Catalytic dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila LDH-osmate of the formula Ila (0.02 Eq. Wt.), N-methylmorpholine-N-oxide (1.5 Eq. Wt) and trans-stilbene (1.0 Eq. Wt) in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1) were stirred at room temperature for 6 hours. After the reaction LDH- osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The pure product, 1,2-diphenyl-1,2-ethandiol was obtained by removing the solvent at reduced pressure followed by column chromatography. (yield 93%). The experimental results in the Examples 9 to 24 were tabulated in Table 1&2. Table 1. Reuse of catalyst IIa for asymmetric dihydroxylation reaction of trans-stilbene (Table Removed) Table 2. Catalytic asymmetric dihydroxylation reaction of olefins by using LDH-osmates of the formulas IIa-IId (Table Removed) "Equivalent weight ratio of the reactants = olefin: osmium: cinchona alkaloid = 1:0.02:0.02, reaction temperature 25°C. b Yield percent after the separation by using column chromatography. c % e.e.(e.e. means enantiomeic excess) was determined by chiral HPLC d absolute configuration was compared with the [ a ]D values in the literature. The main advantages of the present invention are: 1. A novel and ecofriendly process for asymmetric dihydroxylation of olefins is presented. 2. The present process dispenses the use of soluble, toxic osmium tetroxide or potassium osmate dihydrate instead a heterogeneous reusable LDH-osmates are used. 3. LDH-osmates are prepared and used for asymmetric dihydroxylation of olefins as heterogeneous catalysts. The use of heterogeneous LDH-osmates precludes the presence of osmium in traces with product 4. The enantioselectivity and the yields are good. 5. The work-up procedure is simple. 6. The catalyst is subjected to many recycles, which displayed consistent activity. 7. The present process is environmentally safe since there is no disposal problem. 8. The process is economical. We claim : 1. A process for the preparation of vicinal diol using the recyclable catalyst LDH-osmate which comprises dehydroxylating the olefin by using standard method with recyclable catalyst LDH-osmate in an amount in the range of 0.01 to 3 mol% in the presence of an oxidant such as herein described in a solvent at a temperature in the range of -20 to 100°C for a period 0.5 to 24 h, to obtain the pure product vicinal diol by conventional method, if desired carrying out the above reaction in presence of a cinchona alkaloid compound to obtain the pure product chiral vicinal diol. 2. A process as claimed in claim 1 wherein 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. 3. A process as claimed in claims 1-2 wherein the cinchona alkaloid compound used is selected from the known group consisting of monomeric or polymeric, preferably hydroquinone 1,4-phthalazinediyl diether, hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether, hydroquinidine (anthraquinone-1,4-diyl) diether, hydroquinidine acetate, 0-(4-chlorobenzoyl) hydroquinidine, hydroquinidine 9-phenanthryl ether, hydroquinidine 4-methyl-2-quinolyl ether and other pseudoenantiomeric forms of these ligands. 4. A process as claimed in claims 1-3 wherein the solvent used is selected from the group consisting of water, acetone, acetonitrile, t-butanol and mixture thereof. 5. A process for the preparation of vicinal diol using the recyclable catalyst LDH-osmate substantially as herein described with reference to the examples.

Full Text

The present invention relates to a process for the preparation of vicinal diols using the recyclable catalyst LDH-osmate. More particularly the present invention relates to a process for the preparation of vicinol diol by asymmetric dihydroxylation (AD) of an olefin using the recyclable catalyst LDH-osmates of the formula [M11(i.X) M111x (OH)2][OsO42' ]x/2.zH2O wherein M" is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Mi2"1", Cu2+, Zn2+ and Ca2+; M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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.
The catalyst LDH-osmate of the formula [MII(i.X)MIIIx(OH)2][OsO42"]x/2.zH2O wherein z is the number of water molecules is prepared as described and claimed in our co-pending application no. NF 327/00.
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 ft 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 US patents US 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 US patent US 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 US patent US 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 dihydroxylation 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 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)2PHAL),

hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether ((DHQD)2PYR),
hydroquinidine (anthraquinone-1,4-diyl) diether ((DHQD)2AQN), 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.
Accordingly, the present invention relates to a process for the preparation of vicinal
diol using the recyclable catalyst LDH-osmate which comprises dehydroxylating the
olefin by using standard method with recyclable catalyst LDH-osmate in an amount
in the range of 0.01 to 3 mol% in the presence of an oxidant such as herein
described in a solvent at a temperature in the range of -20 to 100°C for a period 0.5
to 24 h, to obtain the pure product vicinal diol by conventional method, if desired
carrying out the above reaction in presence of a cinchona alkaloid compound to
obtain the pure product chiral vicinal diol.
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 another embodiment of the present invention the LDH-osmate is recovered by
simple filtration and reused for several cycles with consistent activity.
In yet another embodiment the oxidant used is selected from the known group
consisting of N-methylmorpholine N-oxide (NMO), Trimethylamine N-oxide,
hydrogen peroxide, potassium ferricyanide, sodium periodate or molecular oxygen.
A process as claimed in claims 1-4 wherein the cinchona alkaloid compound used is
selected from the known group consisting of monomeric or polymeric, preferably
hydroquinone 1,4-phthalazinediyl diether, hydroquinidine 2,5-diphenyl-4,6-
pyrimidinediyl diether, hydroquinidine (anthraquinone-1,4-diyl) diether,
hydroquinidine acetate, O-(4-chlorobenzoyl) hydroquinidine, hydroquinidine 9-
phenanthryl ether, hydroquinidine 4-methyl-2-quinolyl ether and other
pseudoenantiomeric forms of these ligands.
In still another embodiment the solvent used is selected from the group consisting of
water, acetone, acetonitrile, t-butanol and mixture thereof.
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 [MII(i.x)MIIIx (OH)2][OsO42"]x/2.zH2O wherein M" is a divalent cation selected from the group consisting of Mg2"1", Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+ and M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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"(i.x) Mmx (OH)2][OsO42~]x/2.zH2O is prepared by reacting potassium osmate of formula K2OsO4 2H2O with a LDH of formula [M"(i.X) M'"X (OH)2][An"]x/n.zH20 wherein M" is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+ and M111 is a trivalent ion selected from the group consisting of A13+, Cr3+, Mn3+, Fe3+ and Co3+, 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 [Mn(i.x) Mmx (OH)2][OsO42"]x/2.zH2O wherein M11 is a divalent cation (Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+); M111 is a trivalent ion (A13+, Cr3+, Mn3+, Fe3* or Co3); 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 olefms 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 [MII(1.X)MIIIx(OH)2][OsO42"]x/2-zH2O wherein M11 is a divalent cation selected from the group consisting of Mg2+, Mn2+, Fe2+, Co2+, Ni2+, Cu2+, Zn2+ and Ca2+; M111 is a trivalent ion selected from the group consisting of Al3"1", Cr3+, Mn3+, Fe3+ and Co3+ in catalytic amounts by dihydroxylation of olefms 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)2PHAL, (DHQD)2PYR, (DHQD)2AQN, 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.
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
Example 1 Preparation ofMg2+/Al3+/Cr -LDH (la)
A mixture of MgCl2.6H2O (30.49 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was dissolved in 200 mL of deionised water. The resultant aqueous solution was slowly added at 25°C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH of the reaction mixture was maintained constantly (-10) by the continuous addition of 2 M NaOH. The suspension thus obtained was stirred overnight under a nitrogen atmosphere at 70°C. The solid product was isolated by filtration, washed thoroughly with deionised water, and dried overnight at 80°C. Decarbonated water was used in all the synthetic steps. Mg2VAl3+/Cl~ hydrotalcites of the different Mg/Al ratios were also prepared similarly, using appropriate amounts of magnesium chloride hexahydrate and aluminium chloride hexahydrate.
Example 2
Preparation of Mg2+/Al3+/NO3~ -LDH (Ib)
The Mg2+/Al3+/NO3" hydrotalcite with a Mg/Al ratio of 3:1 was prepared from magnesium nitrate hexahydrate (30.8 g, 0.12 mol) and aluminum nitrate nonahydrate (15.0 g, 0.04 mol) which were dissolved in 100 ml of deionised and decarbonated water. The pH of the solution was adjusted to -10 by the addition of NaOH (2M). The slurry was stirred for 2 h at room
temperature under nitrogen atmosphere and then filtered under nitrogen atmosphere, washed thoroughly and dried under vacuum at 80°C.
Example 3
Preparation of MS2+/Al3+/CO32' -LDH (Ic)
A mixture of 60.09 g of Mg(NO3)2.6H2O (0.234 mol) and 29.31 g of A1(NO3)3.9H2O (0.078 mol) in 70 ml distilled water was added to a solution of 28.12 g, 50% aq. NaOH (0.703 mol) and 22.08 g Na2CO3 (0.41 mol) in 100 ml distilled water. The addition was carried out slowly in a 500 ml flask equipped with a mechanical stirrer and the resultant heavy slurry was heated at 65 ± 5°C for about 18 h. The slurry was allowed to cool to room temperature, filtered and washed. The solid was then dried and calcined at 450°C for 6h in airflow.
Example 4
Preparation of M2+/Al3+/Cr - LDH (Id)
A mixture of NiCl2.6H2O (35.65 g. 0.15 mol) and A1C13.6H2O (12.07 g. 0.05 mol) was dissolved in 200 mL of deionised water. The aqueous solution was slowly added at 25 °C to 100 mL of NaOH solution at pH 10 while stirring under a nitrogen flow. The pH was constantly maintained (-10) by the continuous addition of 2 M NaOH. The suspension was stirred overnight under a nitrogen atmosphere at 70°C. The solid product was isolated by filtration, washed thoroughly with deionised water, and dried overnight at 80°C. All synthetic steps were carried out using decarbonated water. Preparation of LDH-osmates
Example 5
Preparation of (MgAl)LDH-OsO42' (IIa)
1g of la was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product is filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 25.6 % of osmium. This means that 1.345 mmol of osmium per 1 gram of the product. The release of equivalent amounts of chloride ions were also quantitatively estimated by titration of the combined filtrates with 0. IN AgNO3 solution in presence of KCrO4 indicator.
Example 6
Preparation of (MgAl)LDH-OsO42~ (II b)
Ig of Ib was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 18.4 % of osmium. This means that 0.966 mmol of osmium per 1 gram of the product.
Example 7
Preparation of (MgAl)LDH-OsO42' (IIe)
Ig of calcined Ic was suspended in 100 ml of 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25°C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 19.95 % of osmium. This means that 1.048 mmol of osmium per 1 gram of the product.
Example 8
Preparation of (NiAl)LDH-OsO42' (IId)
Ig of Id was suspended in 100 ml of a 1.87 mmol (0.688g) aqueous potassium osmate solution and stirred at 25 °C for 24 h under N2 atmosphere. The solid product was filtered, washed with decarbonated water and vacuum dried. Chemical analysis showed that the product contains 24.2 % of osmium. This means that 1.271 mmol of osmium per 1 gram of the product. The release of equivalent amounts of chloride ions were also quantitatively estimated by titration of the combined filtrates with 0.1N AgNOa solution in presence of KCrO* indicator. Asymmetric Dihydroxylation of Olefins
The asymmetric dihydroxylation reaction of olefins was performed using the following two methods in order to evaluate LDH-osmates of the present invention. Method I
LDH-osmates of the formula IIa-IId (0.02 eq. wt. of osmium content in the LDH), cinchona alkaloid (DHQD)2PHAL (0.02 Eq. Wt.) and N-methylmorpholine-N-oxide (1.5 Eq. Wt.) were stirred for 30 min in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1). To this mixture was added an olefin (1.0 Eq. Wt). After the reaction, the LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The concentrated organic layer was purified to afford the corresponding cis-diol by using conventional processes. The yield and the optical purity of the product were determined. Method II
LDH-osmate of the formula Ila-IId (0.002.about.0.02 Eq. Wt. of osmium content in the LDH), cinchona alkaloid (DHQD)2PHAL (0.02 Eq. Wt.),-.potassium ferricyanide (K3 Fe(CN)6, (3.0 Eq. Wt.) and potassium carbonate (K2 CO3, 3.0 Eq. Wt.) were stirred for 30 min in the mixed solvent of tert-butanol/water (in the volume ratio of 1:1). To this mixture
was added an olefin (1.0 Eq. Wt). After the reaction, LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The concentrated organic layer was purified to afford the corresponding cis-diol by using conventional processes. The yield and the optical purity of the product were determined.
Catalytic asymmetric dihydroxylation of olefins using N-methylmorpholine-N-oxide as a co-oxidant
Example 9
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa
LDH-osmate of the formula IIa (0.02 Eq. Wt.), Hydroquinidine 1,4-phthalazinediyl diether ((DHQD)2PHAL) (0.02 Eq. Wt.) and N-methylmorpholine-N-oxide (1.5 Eq. Wt.) were stirred for 30 min in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1). To this mixture was added trans-stilbene (1.0 Eq. Wt) and stirred at room temperature for 6 hours. After the reaction, LDH-osmate catalyst was filtered off and washed with methanol. The combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The pure product was obtained by removing the solvent at reduced pressure followed by column chromatography. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%) [α]D +92.44 (c 1.0, EtOH): e.e.=99.4%
Example 10
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 9 without further addition of osmate catalyst. The reaction was performed using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 95%) [oc]D +92.90 (c 1.0, EtOH): e.e.=99.9%
Example 11
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 10 without further addition of LDH-osmate catalyst.
»he reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 97%) [α]D+92.16 (c 1.0, EtOH): e.e.=99.1%
Example 12
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 11 without further addition of LDH-osmate catalyst.
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 97.0% of enantiomeric excess was obtained (yield 94%) [α]D +90.76 (c 1.0, EtOH): e.e.=97.6%
Example 13
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa which had been used in Example 12 without further addition of LDH-osmate catalyst.
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%) [α]D +92.81 (c 1.0, EtOH): e.e.=99.8%
Example 14
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila which had been used in Example 13 without further addition of LDH-osmate catalyst.
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 98%) [α]D +92.25 (c 1.0, EtOH): e.e =99.2%
Example 15
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by LDH-osmate of the formula IIb
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 97%) [α]D +92.34 (c 1.0, EtOH): e.e =99.3%
Example 16
Catalytic asymmetric dihydroxylation reaction of trans-stilbene. by using LDH-osmate of the formula IIc
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-1,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 95%). [α]D +92.53 (c 1.0, EtOH): e.e.=99.5%
Example 17
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IId
The reaction was performed by using an identical process as in Example 9. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 99.0% of enantiomeric excess was obtained (yield 96%). [Α]D +92.25 (c 1.0, EtOH): e.e.=99.2%
Example 18
Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula IIa
The reaction was performed by using an identical process as in Example 9 except the cinchona alkaloid is DHQD-CLB. (R,R)-(+)-l,2-diphenyl-l,2-ethandiol of more than 98.0% of enantiomeric excess was obtained (yield 92%) [α]D + 91.32 (c 1.0, EtOH): e.e.=98.2%
Example 19
Catalytic asymmetric dihydroxylation reaction of styrene by using LDH-osmate of the formula IIa
The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (R)-phenyl-1,2-ethanediol of more than 95.0% of enantiomeric excess was obtained (yield 94%) [α]D -34.29 (c 1.0, EtOH): e.e.=95.7%
Example 20
Catalytic asymmetric dihydroxylation reaction of trans-beta.-methyl styrene by using LDH-osmate of the formula IIa
The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (R,R)-l-phenyl-l,2-propanediol of more than 98.0% of enantiomeric excess was obtained (yield 97%) [α]D -30.50 (c 1.0, EtOH): e.e.=98.1%
Example 21
Catalytic asymmetric dihydroxylation reaction of methyl trans-cinnamate by using LDH-osmate of the formula IIa
The reaction was performed by using an identical process as in Example 9 except slow addition of olefin with a reaction time of 12 hours. (2S,3R)-2,3-dihydroxy-3-phenylpropionate of more than 97.0% of enantiomeric excess was obtained (yield 96%) [α]D -10.46 (c 1.0 , CHC13): e.e.=97.8%
Example 22
Catalytic asymmetric dihydroxylation reaction of allyl 1-naphthyl ether by using LDH-osmate of the formula IIa
The reaction was performed by using an identical process as in Example 9.1 except slow addition of olefin with a reaction time of 12 hours. 2,3-dihydroxypropyl-1-naphthyl ether of more than 77.0% of enantiomeric excess was obtained (yield 94%) [α]D +5.18 (c 1.0, CH3OH): e.e.=77.4%
Example 23
Catalytic asymmetric dihydroxylation of olefins using potassium ferricyanide as a co-oxidant Catalytic asymmetric dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila
LDH-osmate of the formula Ila (0.02 Eq. Wt.), bis-cinchona alkaloid of the formula (DHQD)2PHAL (0.02 Eq. Wt.), potassium ferricyanide (K3Fe(CN)6,3.0 Eq. Wt.) and potassium carbonate (K2CO3, 3.0 Eq. Wt.) were stirred for 30 min in the mixed solvent of tert-butanol/water (in the volume ratio of 1:1). To this mixture was added trans-stilbene (1.0 Eq. Wt). After a reaction time of 6 hours, LDH-osmate catalyst separated by filtration. After washing with methanol, combined filtrates were concentrated under reduced pressure. The chiral ligand was recovered from the aqueous layer after acidification (IN HC1). The pure product was obtained by removing the solvent at reduced pressure followed by column chromatography. (S,S)-(-)-l,2-diphenyl-l,2-ethanediol of more than 99.0% of enantiomeric excess was obtained (yield 95%). [α]D +92.90 (c 1.0, EtOH): e.e.=99.9%
Example 24
Catalytic dihydroxylation reaction of trans-stilbene by using LDH-osmate of the formula Ila LDH-osmate of the formula Ila (0.02 Eq. Wt.), N-methylmorpholine-N-oxide (1.5 Eq. Wt) and trans-stilbene (1.0 Eq. Wt) in the mixed solvent of water/acetone/acetonitrile (in the volume ratio of 1:1:1) were stirred at room temperature for 6 hours. After the reaction LDH-

osmate catalyst was filtered off and washed with methanol. The combined filtrates were
concentrated under reduced pressure. The pure product, 1,2-diphenyl-1,2-ethandiol was
obtained by removing the solvent at reduced pressure followed by column chromatography.
(yield 93%).
The experimental results in the Examples 9 to 24 were tabulated in Table 1&2.
Table 1. Reuse of catalyst IIa for asymmetric dihydroxylation reaction of trans-stilbene

(Table Removed)
Table 2. Catalytic asymmetric dihydroxylation reaction of olefins by using LDH-osmates of the formulas IIa-IId

(Table Removed)
"Equivalent weight ratio of the reactants = olefin: osmium: cinchona alkaloid =
1:0.02:0.02, reaction temperature 25°C.
b Yield percent after the separation by using column chromatography.
c % e.e.(e.e. means enantiomeic excess) was determined by chiral HPLC
d absolute configuration was compared with the [ a ]D values in the literature.
The main advantages of the present invention are:
1. A novel and ecofriendly process for asymmetric dihydroxylation of olefins is presented.
2. The present process dispenses the use of soluble, toxic osmium tetroxide or potassium
osmate dihydrate instead a heterogeneous reusable LDH-osmates are used.
3. LDH-osmates are prepared and used for asymmetric dihydroxylation of olefins as
heterogeneous catalysts. The use of heterogeneous LDH-osmates precludes the presence
of osmium in traces with product
4. The enantioselectivity and the yields are good.
5. The work-up procedure is simple.
6. The catalyst is subjected to many recycles, which displayed consistent activity.
7. The present process is environmentally safe since there is no disposal problem.
8. The process is economical.

We claim :
1. A process for the preparation of vicinal diol using the recyclable catalyst
LDH-osmate which comprises dehydroxylating the olefin by using
standard method with recyclable catalyst LDH-osmate in an amount in the
range of 0.01 to 3 mol% in the presence of an oxidant such as herein
described in a solvent at a temperature in the range of -20 to 100°C for a
period 0.5 to 24 h, to obtain the pure product vicinal diol by conventional
method, if desired carrying out the above reaction in presence of a
cinchona alkaloid compound to obtain the pure product chiral vicinal diol.
2. A process as claimed in claim 1 wherein 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.
3. A process as claimed in claims 1-2 wherein the cinchona alkaloid
compound used is selected from the known group consisting of
monomeric or polymeric, preferably hydroquinone 1,4-phthalazinediyl
diether, hydroquinidine 2,5-diphenyl-4,6-pyrimidinediyl diether,
hydroquinidine (anthraquinone-1,4-diyl) diether, hydroquinidine acetate,
0-(4-chlorobenzoyl) hydroquinidine, hydroquinidine 9-phenanthryl ether,
hydroquinidine 4-methyl-2-quinolyl ether and other pseudoenantiomeric
forms of these ligands.
4. A process as claimed in claims 1-3 wherein the solvent used is selected
from the group consisting of water, acetone, acetonitrile, t-butanol and
mixture thereof.
5. A process for the preparation of vicinal diol using the recyclable catalyst
LDH-osmate substantially as herein described with reference to the
examples.

Documents:

349-del-2001-abstract.pdf

349-del-2001-claims.pdf

349-del-2001-correspondence-others.pdf

349-del-2001-correspondence-po.pdf

349-del-2001-description (complete).pdf

349-del-2001-form-1.pdf

349-del-2001-form-2.pdf

349-del-2001-form18.pdf

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Patent Number

226248

Indian Patent Application Number

349/DEL/2001

PG Journal Number

01/2009

Publication Date

02-Jan-2009

Grant Date

15-Dec-2008

Date of Filing

27-Mar-2001

Name of Patentee

COUNCIL OF SCIENTIFIC AND INDUSTRIAL RESEARCH

Applicant Address

RAFI MARG, NEW DELHI-110 001, INDIA.

Inventors:

#	Inventor's Name	Inventor's Address
1	BOYAPATI MANORANJAN CHOUDARY	INDIAN INSTITUTI OF CHEMICAL ECHNOLOGY HYDERABAD-500001,ANDHRA PRADESH,INDIA.
2	NAIDU SREENIVASA CHOWDARI	INDIAN INSTITUTI OF CHEMICAL TECHNOLOGY,HYDERABAD-500001, ANDHRA PRADESH
3	MANNEPALLI LAKSHMI KANTAM	INDIAN INSTITUTI OF CHEMICAL TECHNOLOGY,HYDERABAD-500001, ANDHRA PRADESH
4	KONDAPURAM VIJAYA RAGHAVAN	INDIAN INSTITUTI OF CHEMICAL TECHNOLOGY,HYDERABAD-500001, ANDHRA PRADESH
5	CHINTA REDDY VENKAT REDDY	INDIAN INSTITUTI OF CHEMICAL TECHNOLOGY,HYDERABAD-500001, ANDHRA PRADESH

PCT International Classification Number

B01J 23/652

PCT International Application Number

N/A

PCT International Filing date

PCT Conventions:

#	PCT Application Number	Date of Convention	Priority Country
1			NA