Title of Invention

NOVEL CATALYST AND THEIR APPLICATION IN OXIDATION OF ALCOHOLS

Abstract

A heterogeneous catalyst such as disordered, mesoporous, manganosilicate molecular sieves having pore size in the range of 20°A to 60°A and a process for the preparation of the same are disclosed in this specification. This invention further provides application of said heterogeneous catalyst for oxidation of alcohol with high selectivity towards aldehyde or ketone. Additionally, the invention provides an environmentally benign, commercial oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol to 2-n-butyl-4-chloro-imidazole-5-carboxaldehyde using said heterogeneous catalyst in conjunction with ammonium peroxydisulphate as the oxidant.

Full Text

FORM 2 THE PATENT ACT 1970 (39 of 1970) & The Patents Rules, 2003 COMPLETE SPECIFICATION (See section 10 and rule 13) 1. TITLE OF THE INVENTION: "Novel Catalyst and Their Application In Oxidation Of Alcohols" 2. APPLICANT (S): (a) NAME: IPCA LABORATORIES LIMITED (b) NATIONALITY: Indian Company incorporated under the Indian Companies ACT, 1956 (c) ADDRESS: 48 Kandivli Industrial Estate, Mumbai - 400 067, Maharashtra, India 3. PREAMBLE TO THE DESCRIPTION: The following specification particularly describes the invention and the manner in which it is to be performed. TECHNICAL FIELD This invention relates to synthesis of manganosilicate molecular sieves and their application as catalyst into oxidation of alcohol to aldehyde. More specifically the invention relates to environmentally benign process for oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol using said catalyst & ammonium peroxydisulphate as the oxidizing agent. BACKGROUND OF THE INVENTION In current industrial practice, stoichiometric inorganic oxidants, such as permanganate, dichromate and activated manganese oxides are employed to perform oxidation of various substrates into corresponding aldehydes or acids. However, these oxidation routes generate large amounts of waste inorganic salts (pollutants) that are extremely difficult to dispose of and economically impractical to recycle. Therefore, there is a growing demand for developing cleaner, catalytic and more selective alternatives to existing oxidation processes. Moreover, most of these catalysts are not specific for oxidation of alcohol into aldehydes and generally the oxidations are not controllable at the aldehyde stage and over oxidation to acids is a general concern. In this context, metal containing molecular sieves offer tremendous potential as catalysts for heterogeneous oxidation. A pioneering class of silica-based mesoporous molecular sieves, designated as M41S, was synthesized by Mobil researchers (Kresge et al, Nature 359, 1992, 710). Later, silica-based M41S molecular sieves were modified by incorporation of transition metals into the framework. Substitution of metal cations with redox properties such as Ti, V and Co generates novel heterogeneous catalysts for liquid phase oxidation. Titanium containing TS-1 was found to be an effective oxidation catalyst for a variety of organic compounds using aqueous hydrogen peroxide as oxidant (Taramasso et al, US 4,410,501). However, because of the small pore size the number of the organic compounds that can be oxidized by TS-1 is strongly limited to molecules having kinetic diameters equal to or less than about 6 °A. Another titanium silicalite, TS-2, with MEL structure was reported to exhibit similar oxidation properties (Reddy et al, J. Catal., 130, 440-446 (1991)), however the preparation of this molecular sieve involved the use of charged (S+) quaternary ammonium template (TBA+) and prolonged hydrothermal conditions. V-substituted silicalite-1 and 2 (denoted VS-1 and VS-2) oxidation catalysts were also reported (Reddy et al., Catal. Lett. 28, 263-267 (1994) and Rao et al, J. Catal. 141(2) 604-611 (1993)). However, due to the embedding of V in the same silicalite microporous framework the catalytic oxidation activity of these molecular sieves was again limited to small organic substrates with kinetic diameters of less than 6 °A. Cobalt substituted aluminophosphate molecular sieves (denoted CoAPO) are also reported for oxidation of saturated hydrocarbons, but the conversion of framework Co between Co(II) and Co(III) is controversial (Kraushaar-Czarnetzki et al, Stud. Surf. Sci. and Catal., 69, 231 (1991)). Recently, mesoporous manganese silicates having hexagonal, cubic and lamellar structures were reported (Zhao et al, J. Chem. Soc, Chem. Commun., 875 (1995), but again the synthesis of these materials involved the use of prolonged hydrothermal conditions. The present invention discloses a new process for the synthesis of disordered mesoporous manganosilicates having pore size in the range of 20 - 50 °A. The large pore size proved to be advantageous as the catalytic oxidation activity of the material was extended to the bulkier alcoholic substrates. It is of broader industrial interest to design a new environmentally benign protocol for oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol using a heterogeneous catalyst such as manganosilicate molecular sieve catalyst in conjunction with peroxydisulphate as the oxidizing agent. The current process for the oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol employs at least 3.5 molar equivalents of activated manganese oxide. Disadvantages of this process include use of excess amount of manganese oxide that results into generation of huge amounts of spent/unspent manganese oxide for which there is no easy means of disposal and processing difficulties in removing the manganese dioxide as well as its by-product from the reaction mixture.. Heterocyclic alcohols have been converted to aldehydes with peroxydisulphate oxidant using silver nitrate as the homogeneous catalyst (Brossmer et al., Tet. Lett. 5253 (1966)). Benzylic alcohols have been successfully oxidized to benzaldehydes with peroxydisulphate in presence of Iron (II) sulfate and copper (II) acetate as the catalyst, however the method failed for oxidation of imidazole alcohols (A. Citterio et al., La Chimica e L 'Industria, 64, 320 (1982)). The present invention discloses a novel protocol for heterogeneous oxidation of heterocyclic alcohols, where catalyst can be regenerated and recycled. OBJECTIVE OF THE INVENTION The basic objective of the present invention is to provide heterogeneous catalysts for the oxidation of alcohol with high selectivity towards aldehydes. Another objective of the present invention is to provide a process for producing heterogeneous solid catalyst such as manganosilicate molecular sieves. Yet another object of the invention is to develop commercial process for oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol with an advantage of superior control over extent of oxidation, desired product selectivity, safety and environmental friendliness that lead to cleaner effluents using the new catalyst. SUMMARY OF THE INVENTION In one aspect, the present invention provides a process for synthesis of disordered mesoporous manganese silicate molecular sieves useful as a heterogeneous catalyst for oxidation of alcohols to aldehydes. In a second aspect the present invention discloses an environmentally benign process for oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol using manganese silicate molecular sieves as a heterogeneous catalyst and a peroxydisulphate compound as the oxidizing agent. The new process of oxidation of alcohols disclosed in present invention has utility in all fields of chemical production including, but not limited to, preparation of pharmaceutical compounds and/or intermediates thereof. DETAILED DESCRIPTION OF THE INVENTION As used herein, manganosilicate molecular sieves belong to the class of silica-based mesoporous molecular sieves, designated and synthesized by Mobil researchers as M41S. The latter are structurally modified by incorporation of manganese atoms into the silica framework. As used herein, the process of synthesis of manganosilicate molecular sieves involves the interaction between the inorganic precursor and the organic template. The method is based on hydrogen bonding and self-assembly between inorganic precursor and the surfactant head group. The present process includes i) providing a manganese silicate composite by adopting a complexing procedure by mixing a) A neutral hexadecyl amine, b) An organic acid, c) Manganese source like potassium permanganate, d) An organic solvent, e) Water, and f) A tetra alkyl orthosilicate compound; and ii) calcining the said material at about 400 to 600 degree celsius for suitable period to obtain the manganosilicate molecular seives of pore size 20 °A to 60 °A. In another aspect the present invention provides application of the manganese silicate molecular sieves in the oxidation of alcohols to aldehydes in presence of an oxidizing agent with high selectivity and specificity. Moreover this process includes methods for recycling the heterogeneous catalyst of the present invention. In the present invention an exemplary heterogeneous oxidation protocol was designed by employing manganosilicate molecular sieves catalyst using peroxydisulphate as the oxidising agent. In accordance with the embodiment of the present invention, 2-n-butyl-4-chloro-imidazole-5-alcohol is oxidized to the corresponding aldehyde as illustrated by the following scheme: Above transformation is carried out by treating the alcoholic substrate (Formula I) with aqueous peroxydisulphate in water, optionally in the presence of an organic solvent such as butyl chloride or acetonitrile in presence of the mesoporous manganese silicate catalyst. The presence of an organic solvent is not essential for the reaction to proceed, as the reaction can be performed completely in aqueous medium. The reaction is carried out at a temperature in the range of 20 - 100 °C. The product can be isolated from the reaction mixture after extraction followed by crystallization from suitable organic solvent. Moreover, the isolation and purification of the resulting product 2- n-butyl-4-chloro-imidazol-5- carbaldehyde is made easy in the present invention by filtering out the catalyst and extraction of the product into a suitable organic solvent. Evaporating the organic extract to eliminate the extraction solvent and optionally crystallized the residue from hexane to yield highly pure 2- n-buty-4-chloro-imidazol-5- carbaldehyde. The invention is now described in greater detail by way of examples given below which are provided by way of illustration only and should not be constructed to limit the scope of the present invention. Example 1 Synthesis of Manganosilicate molecular sieves: A solution of 12 g hexadecyl amine in 150 ml of ethanol was prepared. 3 g of maleic acid was added in parts, which results in the slurry formation. 300 ml of ethanol was added and solution stirred for one hour. To this solution, simultaneously KMnO4 (10 g dissolved in 100 ml of distilled water) and 42 ml of tetraethyl orthosilicate (TEOS) were added dropwise with vigorous stirring. Brown coloured gel formed was stirred for two hours and then allowed to age for 24 hours at the ambient temperature. The upper water layer was decanted and material was air dried on a glass plate. The as synthesised manganosilicate was calcined at 550 °C in air for 5 hours. Oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol catalyzed by manganosilicate catalyst Reaction Methodology The liquid phase oxidation of alcohol was carried out with manganosilicate molecular sieve as the catalyst and ammonium peroxydisulphate as the oxidizing agent. The alcohol substrate containing aqueous phase was initially acidified with H2SO4 and the catalyst mixed with n-chlorobutane was added and stirred mechanically. Required amount of aqueous persulfate solution was added continuously with the help of a peristaltic pump. The reaction was performed in a water bath assembly, where the desired temperatures were properly maintained. Method of Analysis 2-n-butyl-4-chloro-imidazole-5-alcohol was analyzed by Water's Aliance HPLC system equipped with 2695 sample handling unit and 2487 UV detector (X = 240 nm). Water's Atlantis (C-18) (250 x 4.6 mm x 5 μ) column was used with buffer (0.18 g NaH2PO4 + 1.18 g Na2HPO4 in 1 litre deionised water, pH 7 with ortho phosphoric acid): acetonitrile (65:35) mobile phase. Synthetic mixtures were prepared and used for calibration and quantification. GC-MS and LC-MS confirmed the products. Chemical processes catalyzed with the said catalyst produce no inorganic salts and offer different process configurations of semi batch as well as batch process. This methodology can replace advantageously conventional hazardous stoichiometric catalysts. Chemical processes mentioned in this invention are environmentally clean and fit well into the domain of green chemistry. General Example Reaction Conditions; Alcohol: 0.005 - 0.25 mol, solvent: 25 cm3, Catalyst loading: 0.005 - 0.05 g/cm3, persulfate addition rate: 0.1-1 mmol/min, Temperature: Ambient - Reflux, Time: 1 - 5 h., Agitation speed: 200 -1000 rpm. Example 2 Water and n-chlorobutane as reaction medium: Liquid phase oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol was performed in a mechanically agitated reaction vessel with a reflux condenser. The reaction mixture contained 0.025 mol 2-n-butyl-4-chloro-imidazole-5-alcohol, 0.9 cm3 H2SO4 (98 %), 25 cm3 water and 35 cm3 n-chlorobutane. 0.75 gm of the manganosilicate catalyst with a specific catalyst loading of 0.01 g/cm3 was added and stirring maintained at 700 rpm. Temperature of the reaction mixture was maintained at reflux and aqueous solution of ammonium peroxy disulfate was added for 2 hours at the constant rate of 0.3 mmol/min in a semi-batch mode. Reaction was continued for 4 hours after addition of ammonium peroxy disulfate was completed. Heating was stopped and the reaction mixture was cooled to 30 °C-33 °C. The reaction mass was extracted with methylene dichloride (MDC), and stirred for 10-15min (30mlX3) and separated the two layers. MDC layer was washed with 1% NaHCO3 (20mlX2) and separated the organic layer. MDC layer was washed with 20ml of DM water, separated the organic layer and distilled off MDC completely under vacuum. The material was dried in vacuum oven (~40-50mm) at 45oC to 50 °C for 5h. Dry Weight: 3.9g (75% yield) with 97% HPLC purity. Example 3 Water as a reaction medium: Liquid phase oxidation of 2-n-butyl-4-chloro-imidazole-5-alcohol was performed in a mechanically agitated contactor made of glass and a reflux condenser. The reaction mixture contained 0.025 mol 2-n-butyl-4-chloro-imidazole-5-alcohol, 0.9 cm3 H2SO4 (98 %) and 40 cm water. 0.75 gm of the manganosilicate catalyst with a specific catalyst loading of 0.01 g/cm was added and stirring maintained at 700 rpm. Temperature of the reaction mixture was maintained at 70 °C and aqueous solution of ammonium peroxy disulfate was added for 2 hours at the constant rate of 0.3 mmol/min in a semi-batch mode. Reaction was continued for 4 hours after addition of ammonium peroxy disulfate was completed. Heating was stopped and cooled the reaction mixture to 30 °C-33 °C. The reaction mass was extracted with MDC, stirried for 10-15min (30mlX3) and separated the two layers. MDC layer was washed with 1% NaHC03 (20mlX2) and separated the organic layer. MDC layer was washed with 20ml of DM water. The organic layer was separated and distilled off MDC completely under vacuum. The material was dried in vacuum oven (~40-50mm) at 45°C to 50 °C for 5h. Dry Weight: 3.4g (65% yield) with 91% HPLC purity. Example 4 Regeneration of catalyst: The manganosilicate catalyst (example 1) was filtered from reaction mixture and suspended in methanol in round bottom flask and stirred for 1 hour. The catalyst was air dried at 45 °C for 4 hours and calcined at 300 °C. The regenerated catalyst was tested for its reusability. Example 5-7 Reusability of catalyst: The catalyst reusability was studied three times including the use of fresh catalyst. The catalyst was regenerated as described in example 5, before being reused in subsequent batches. In the presence of the fresh catalyst, the isolated yield of aldehyde was 75%, with 97% HPLC purity, while in first reuse of regenerated catalyst, the isolated yield of aldehyde was 71%, with 95% HPLC purity. During the third run (second reusability), the isolated yield decreased to 69 %, while the HPLC purity was 92 %. This decrease in isolated yield of aldehyde is because of the observed losses due to attrition, during filtration of the catalyst particles and no make up quantity of catalyst was added. We claim, 1. A disordered, mesoporous, manganosilicate molecular sieves catalyst having pore size of 20-60° A. 2. Oxidation process of alcohol to aldehyde or ketone in presence of a disordered, mesoporous, manganosilicate molecular sieves catalyst of claim 1. 3. A process for preparation of manganosilicate molecular sieves catalyst having pore size of 20-60°A comprising the steps of: a. creating a manganese silicate composite by mixing a neutral hexadecyl amine, an organic acid, manganese source like potassium permanganate, an organic solvent, water and a tetra alkyl orthosilicate compound; and b. calcining said composite material at a temperature range of 400-600°C for a suitable period to obtain the manganosilicate molecular sieves with a pore size 20- 60°A. 4. A process for oxidation of alcohol to aldehyde or ketone in presence of a disordered, mesoporous, manganosilicate molecular sieves catalyst of claim 1 or 2, which process comprises the steps of: a. providing a reaction mixture by mixing (i) an alcoholic substrate (ii) a catalyst as claimed in claim 1, (iii) one or more solvent (iv) a peroxydic oxidizing agent b. effectuating oxidation of said reaction mixture to obtain the corresponding aldehyde or ketone and recovering said aldehyde or ketone from said reaction mixture. 5. The catalyst for oxidation of alcoholic functional groups as claimed in any one of the preceding claim, wherein the alcoholic functional groups comprises of heterocyclic alcoholic substrates. 6. The process as claimed in claim 4, wherein said alcohol is 2-n-butyl-4-chloro-imidazole-5 -alcohol. 7. The process for selective oxidation of alcohol to aldehyde as claimed in claims 4 or 6 wherein said alcohol is oxidized to 2-n-butyl-4-chloro-imidazole-5-carboxaldehyde. 8. The process as claimed in claim 4 or 7 wherein the peroxydic oxidizing agent is a peroxysulphate compound and is preferably, ammonium preroxydisulphate. 9. The process as claimed in any claim 4 to 8 wherein the solvent is water or an organic solvent such as butyl chloride, acetonitrile or mixture thereof. 10. The catalyst as claimed in any one of the preceding claim, wherein said catalyst is recovered and reused. 11. A process for synthesis of manganosilicate molecular sieves and its application in the preparation of 2-n-butyl-4-chloro-imidazole-5-carboxaldehyde as substantially described herein with reference to the foregoing examples 1 to 7. Dated this 14th day of September 2005 Dr. Gopakumar G. Nair Agent for the Applicant

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1108-mum-2005-abstract(28-7-2008).pdf

1108-mum-2005-abstract.doc

1108-mum-2005-abstract.pdf

1108-mum-2005-cancelled pages(28-7-2008).pdf

1108-mum-2005-claims(granted)-(28-7-2008).pdf

1108-mum-2005-claims.doc

1108-mum-2005-claims.pdf

1108-mum-2005-correspondence(25-7-2008).pdf

1108-mum-2005-correspondence(ipo)-(11-11-2008).pdf

1108-mum-2005-correspondence-received-ver-140905.pdf

1108-mum-2005-correspondence-received.pdf

1108-mum-2005-description (complete).pdf

1108-mum-2005-form 1(14-9-2005).pdf

1108-mum-2005-form 18(14-8-2007).pdf

1108-mum-2005-form 2(granted)-(28-7-2008).pdf

1108-mum-2005-form 26(24-3-2006).pdf

1108-mum-2005-form 26(5-4-2005).pdf

1108-mum-2005-form 3(28-7-2008).pdf

1108-mum-2005-form-1.pdf

1108-mum-2005-form-2.doc

1108-mum-2005-form-2.pdf

1108-mum-2005-form-26.pdf

1108-mum-2005-form-3.pdf

1108-MUM-2008-ABSTRACT(25-07-2008).pdf

1108-MUM-2008-CLAIMS(25-07-2008).pdf

1108-MUM-2008-CORRESPONDENCE(25-07-2008).pdf

1108-MUM-2008-DESCRIPTION(COMPLETE)-(25-07-2008).pdf

1108-MUM-2008-FORM 1(25-07-2008).pdf

1108-mum-2008-form 2(25-07-2008).pdf

1108-MUM-2008-FORM 2(TITLE PAGE)-(25-07-2008).pdf

1108-MUM-2008-FORM 26(25-07-2008).pdf

1108-MUM-2008-FORM 3(25-07-2008).pdf

1108-MUM-2008-FORM 5(25-07-2008).pdf