Title of Invention	PROCESS FOR CONDUCTING DEHYDRATION REACTION USING METAL NANOPARTICLES
Abstract	This invention relates to a process for conducting dehydration reactions using metal nanoparticles. The nanoparticels are copper or nickel nanoparticles which are prepared in a reverse micellar system. The metal nanoparticles are used to catalyse dehydration reactions such as in Knovenagel condensation or in multi-component coupling reactions.

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FIELD OF THE INVENTION: This invention relates to a process for conducting dehydration reaction using metal nanoparticles. This invention further relates to a process for conducting dehydration reactions using metal nanoparticles, in particular nickel and copper nanoparticles, under mild conditions. BACKGROUND OF THE INVENTION: Dehydration is a common step occurring in most organic reactions and sometimes the key step in a number of reactions for the preparation of important carbon-carbon skeletons. The Knoevenagel condensation is a useful carbon-carbon bond forming reaction, involving a step of dehydration. Knoevengel reaction has numerous applications in the synthesis of fine chemicals, hetero-Diels- Alder reactions and the synthesis of carbocyclic as well as hetero cyclic compounds. The reaction has been utilized in the preparation of coumarin derivatives, cosmetics, perfumes and pharmaceutical chemicals. Traditionally, this condensation has been carried out between a carbonyl compound and an active methylene compound in the presence of bases such as ethylenediamine, piperidine or corresponding ammonium salts, amino acids, dimethylaminopyridine and potassium fluoride mixture. Recently, efforts have been made to prepare electrophilic alkenes by conducting this reaction under heterogeneous conditions using inorganic salts like AL2O3, zeolite and calcite. Ionic liquids have also played a vital role as a reaction media for this condensation. However, some of these processes require harsh conditions and suffer from a lack of generality. In the process disclosed by Leelavathe etal al (J. Mol. Catalyst: A 2005, 240, 99). NbCl5 catalyst is used, which leads to a 93% yield of the condensed product, but the time required for the reaction is 1320 min. Further, Reddy etal (Tetrahedron Lett, 1997, 38, 1721) teaches a condensation method under heterogeneous conditions using zeolite, which leads to a 78% yield over a period of 720 min. Also, disclosed is a process by Yamawaki et al, where the inventors have used KF/AL2O3 as the catalyst for the condensation reaction, over a period of 150 min to arrive at a yield of 80%. Rao and Venkatraman (Tetrahedron Lett, 1991,32, 5821) have reported a condensation reaction using ZnCb as the catalyst. However, although the reaction time is 10 min, a temperature of 100°C has been employed to arrive at a yield of 91%. In typical cases when metal salts and other complexes are used as catalysts, an excessive amount of catalysts (usually in grams) is needed and this is eliminated as a Svaste product' and is often toxic. Hence there is an existing need for the development of milder methods for obtaining these products under conditions tolerated by sensitive functional groups from both synthetic and environmental points of view. The synthetic challenge is to carry out this reaction in a neutral medium thus avoiding the use of bases. The multi-component coupling reaction are emerging as a useful source for synthesizing small drug-like molecules with several levels of structural diversity and these reactions often involve dehydration reactions for the generation of intermediates and final products. They are also welcome in the context of economic and practical considerations. Moreover, multi-component coupling strategies offer significant advantages over conventional linear-type synthesizes. In such reactions, three or more reactants come together in a single reaction vessel to form new products. Solid phase peptide synthesis is a pertinent example that immediately comes to mind. The search and delivery for new multi- component coupling reactions on one hand and the full exploitation of the already known multi-component reactions on the other hand, is therefore of considerable current interest. Thiazolidinediones (TZDs), also known as glitazones, are a class of chemotherapeutics that increase sensitivity to insulin and are used for the treatment of type 2 diabetes mellitus. They increase the action of insulin in the liver, muscle and fat tissues. TZDs lower liver glucose production and enhance glucose uptake by the muscle and the fat cells. TZDs bind to and activate the nuclear receptor peroxisome-proliferator activated receptor γ (PPARγ) which in turn triggers the expression of insulin-responsive genes responsible for the regulation of carbohydrate and lipid metabolism. Consequently, TZDs raise high-density lipoprotein (HDL) and tend to have variable effects on both low -density lipoprotein (LDL) and triglyceride levels. TZDs display a marked lowering of glycosylate haemoglobin (HbA1c) mean values, a prognosticator of serious diabetes complications. Currently two TZDs are used clinically in the US, rosiglitazone (Avandia) and pioglitazone (Actos). However in spite of their effectiveness, TZD are not used as widely as sulfonylureas and metaformin purportedly because of safety concerns and also because TZDs are relatively expensive. In this regard, thiaglitazone (a TZD analog) has been temporarily withdrawn because of liver toxicity; however other TZD analogues like rosiglitazone and pioglitazone eliminate the risk of hypoglycaemic episodes unlike sulphonylureas. This is because of the differences in their stated modes of action. While sulphonylureas act mainly by increasing insulin secretion, TZDs act on the nuclear PPARγ receptors and enhance transcription of several insulin sensitive genes. This process also has the added advantage of decreasing insulin resistance. Several synthetic approaches for the synthesis of TZDs are given in the literature but most of the compounds that have been synthesized so far are insignificant because most of these methods give unsatisfactory product yield even after prolonged reaction time. They also have critical product isolation procedures, use expensive and detrimental metal precursors and volatile organic solvents and require harsh reaction conditions such as high reaction temperature and a strong acidic media. Hence, there is a strong need to synthesize TZDs in more eco-friendly conditions. OBJECTS OF THE INVENTION: It is therefore an object of this invention to propose a process for conducting dehydration reactions which uses mild reaction conditions. It is a further object of this invention to propose a process for conducting dehydration reactions which is eco-friendly and environmentally benign. Another object of this invention to propose a process for conducting dehydration reactions which is simple, involves simple steps of reaction, work-up and isolation and is cost effective. Yet another object of this invention to propose a process for conducting dehydration reactions, which has a wide range of substrate applicability. These and other objects of the invention will be apparent from the ensuing description. SUMMARY OF THE INVENTION: This invention relates to a process for conducting dehydration reactions using metal nanoparticles. The nanoparticels are copper or nickel nanoparticles which are prepared in a reverse micellar system. The metal nanoparticles are used to catalyse dehydration reactions such as in Knovenagel condensation or in multi-component coupling reactions. BRIEF DESCRIPTION OF THE INVENTION: Thus according to this invention is provided a process for conducting dehydration reactions using metal nanoparticles. In accordance with this invention, metal nanoparticles are used in dehydration reactions. The metal nanoparticles used are nickel and copper nanoparticles but are not restrinted to them while the dehydration reactions include but are not limited to Knoevengel condensation reactions and multi-component coupling reactions such as for the synthesis of thiazolidine 2,4-dione derivatives using mild, eco- friendly and environmentally benign conditions. A chemical method involving reduction of Ni2+-ions to Ni (0) and Cu2+ to Cu (O) in a reverse micellar system is employed to prepare the Nickel-or copper nanoparticles (Scheme-1). A surfactant, solvent (continuous phase), and a co-surfactant and aqueous solution of salts as dispersed phase (water core in which particle formation occurs) and are used to form the nanoparticle. The reverse micelles are prepared by dissolving the surfactant in solvent to obtain a solution. To a predetermined volume of the surfactant solution, an aqueous solution of a Nickel salt or a copper salt, followed by the co- surfactant is added to obtain an optically clear reverse micellar solution (RM-1). To another predetermined volume of the surfactant solution, a solution of a reducing agent is added to obtain a second reverse micellar solution (RM-2). To reverse micellar solution of metal (RM-1), the RM-2 is added dropwise with constant stirring, under an inert atmosphere, followed by further stirring to allow complete particle growth. The copper or nickel nanoparticles are extracted by adding absolute ethanol to the reverse micellar solution containing the nanoparticles followed by centrifugation. By varying the water content parameter Wo (defined as the molar ratio of water to surfactant concentration, Wo=H20/[surfactant], the sizes of nanoparticles can be controlled. The surfactant is selected from the group containing anionic, cationic and non-ionic type. Preferably Poly (oxyethylene) (tetra methyl butyl)- phenyl ether, commercially known as Triton X-100 (TX-100) is used as surfactant. The solvent used to form the reverse micelles is a hydrocarbon selected from saturated straight chain or branched chain C6 to C10 hydrocarbon, such as cyclo-hexane. The reverse micelles have a long chain alcohol from butanol to octanol as the cosurfactant. The surfactant is dissolved in the solvent to provide a 0.08 to 0.15 M solution. The Nickel salt is a water soluble salt of Nickel, such as for eg. Ni (NO3)2. The copper salt is water soluble salt of copper such as for eg. CuSO4. The Nickel or copper salt is added to TX-100 solution in Ho 3% w/v and hexanol is added (q.s) to obtain an optically clear reverse micellar solution RM-1. In a preferred embodiment, a 2% w/v solution is used. A reducing agent selected from sodium borohydride and diazine ( N2H2) is used to prepare the reverse micellar solution RM-2. The sodium borohydride is used as an alkaline solution, in which sodium borohydride (3 to 6% w/v) is added in a 2% NaOH (w/v) solution. In a preferred embodiment the sodium borohydride is a 5% w/v solution in 2% NaOH (w/v). An aqueous solution of diazine is used in a concentration of 3 to 6% w/v. According to a preferred embodiment a 5% w/v aqueous solution is employed. After adding RM-1, the mixture is stirred under an inert atmosphere of nitrogen. The sizes of the nickel or copper nanoparticles prepared at W0=5 (the water content parameter WO can be defined as the ratio of molar concentration of water to surfactant, W0=[H2O]/ [surfactant] are confirmed as 15-20 nm through Quasi Elastic Light Scattering (QELS) Data an Transmission Electron Microscopy (TEM). The Ni-nanoparticles prepared are round in shape in black in color (colloidal state). The Cu- nanoparticles prepared are round in shape and brown in color (colloidal state). The sizes of the Cu-nanoparticles prepared at Wo=5 (the water content parameter Wo can be defined as the ratio of molar concentration of water to surfactant, Wo=[H20]/[surfactant] were confirmed as 14-18 nm through Quasi Elastic Light Scattering (QELS) data and Transmission Electron Microscopy (TEM). The Ni-nanoparticles thus prepared are used to catalyze the condensation of active methylene compounds, such as malonic acid, ethyl cyanoacetate, malononitrile and dimedone with aldehydes at room temperature in a neutral medium. The Ni-nanoparticles are added to a mixture of an aldehyde and an active methylene compound. The resulting reaction mixture is stirred for a specified period. After complete conversion, the reaction mixture is diluted and washed with water and brine. The organic layer is dried followed by evaporation of solvent under reduced pressure and concentrated to dryness gave the desired product, which followed by recrystalisation afforded the pure Knoevenagel products. The aldehydes are selected from the group of aliphatic aldehydes and aromatic aldehydes such as benzaldehyde and its derivatives such as chlorobenzaldehydes, nitrobenzaldehydes, hydroxybenzaldehydes, anisaldedehydes and any combination of the substituents. Ketones have also been used. The active methylene compounds are selected from malonic acid, ethyl cyanoacetate, malononitrile, dimedone and the like. The aldehyde/ ketone and active methylene compound are used in a 1:1 proportion with a slight excess of the active methylene compound. The Ni-nanoparticle catalyst has a particle size below l00nm preferably between 15 to 20 nm and is used in a proportion between 5-20 mol% per 5 mmol of the aldehyde/ketone. The reaction is conducted at a temperature in the range of 20 to 30°C, preferably at 25°C and over a period of about 1 hour. The reaction mixture is diluted with a polar solvent such as ethyl acetate. The Cu-nanoparticles are used for a simple, stereoselective one-pot three component condensation reaction between thiazolidine-2,4-dione, aldehyde and amine derivative. A solution of thiazolidine-2,4 dione, amine and aldehyde is prepared in a suitable solvent and the resulting mixture is stirred for a few minutes. Copper nanoparticles are added to the solution, and the reaction mixture is stirred at under inert atmosphere for an appropriate reaction time. After the completion of the reaction, the reaction mixture is centrifuged to pellet out the particles. The particles are then washed to remove all the organic impurities. These particles are reused for evaluating the performance in the next reaction. The aldehydes are selected from aromatic aldehydes such as benzaldehyde and derivatives such as chlorobenzaldehydes, nitrobenzaldehydes, hydroxybenzaldehydes, anisaldehydes and any combination of the substituents. The amine is an aromatic amine such as aniline and substituted anilines, where the substituents are selected from methyl, methoxy,benzene diazo and the like. The aldehyde and amine are present in equimolar proportions alongwith a two-fold excess of thiazolidine-2,4-dione. The Cu-nanoparticles are added in a proportion of about 10 mol% per 10 mmol of aldehyde. The solvent used in the reaction is a protic solvent such as methanol, ethanol, polyethylene glycol and the like, preferably methanol. The reaction is conducted at about 45 to 55°C, preferably at about 50°C over a period of about 1 hour. The Cu-nanoparticles used have a particle diameter of 10 to 25 nm, preferably 14 to 18nm. The invention will now be explained in greater detail with the help of the following non-limiting examples. EXAMPLES: The following examples are given by way of illustration of the present invention and should not be constructed to limit the scope of the invention. Example :1 Preparation of Nickel nanoparticles: To a set volume of 100 ml (0.1 M TX-100 solutions in cyclohexane) 900μ1 of Ni (NO3)2 aqueous solution (2% w/v) and hexanol (q.s.) was added to prepare an optically clear reverse micellar solution (RM-1). To another 100 mL (0.1M TX-100 solution in cyclohexane) NaBH4 alk. Solution (5% w/v in 2% NaOH w/v aq. solution) and hexanol (q.s.) was added to obtain RM-2. To the prepared reverse micellar solution of Ni (NO3)2 aqueous solution (2% w/v) (RM-1) another reverse micellar NaBH4 alk Solution (5% w/v in 2% NaOH w/v aq. solution) (RM-2) was added drop wise with constant stirring maintaining the nitrogen atmosphere. In the presence of nitrogen atmospher the resulting solution was allowed for further stirring for three hours to allow complete Ostwald ripening (particle growth. The nickel nanoparticles were extracted by adding absolute ethanol to the reverse micellar solution containing Ni nanoparticles followed by centrifugation at 3000-4000 rpm for 10 minutes. By varying the water content parameter Wo (defined as the molar ratio of water to surfactant concentration, Wo =[H20]/[surfactant] the size of the nanoparticles could be controlled. The sizes of the Nickel- nanoparticles prepared at W0=5 (the water content parameter W0 can be defined as the ratio of molar concentration of water to surfactant, W0=[H2O]/[surfactant] were confirmed as 15-20 nm through Quasi Elastic Light Scattering (QELS) Data and Transmission Electron Microscopy (TEM). The Ni-nanoparticles prepared were round in shape and black in color (colloidal state). Example-2: Procedure for the Ni-nanoparticles catalysed Knoevenagel product: To a mixture of aldehydes (5.0 mmol), active methylene compound (6.0 mmol) in Ethanol (10 ml) was added the catalyst Ni-nanoparticles (15-20 nm, 10 mol%)., the resulting reaction mixture was stirred at room temperature for a specified period (Table 2 ). The progress of the reaction was monitored by thin layer chromatograpy (TLC), after complete conversion, as indicated by TLC; the reaction mixture was diluted by adding Ethyl acetate (50 ml) and washed with water thrice and brine. The organic layer was dried over anhydrous solution sulfate (Na2SO4) followed by evaporation of solvent under reduced pressure and concentrated to dryness gave the desired product, which followed by recrystalisation afforded the pure knoevenagel products in ~ 90 % yield (Table-2). Structural assignments of the products are based on their H- NMR, C-NMR, FT-IR and Mass analysis. The analysis of complete spectral and compositional data revealed other formation of Knoevenagel products with excellent purity. EXAMPLE-3 Preparation of copper nanoparticles: To a set volume of 100 ml (0.1 M TX-100 solutions in cyclohexane) 900 μl of CuS04 aqueous solution (2% w/v) and hexanol (q.s.) was added to prepare an optically clear reverse micellar solution (RM-1). To another 100 ml (0.1 M TX-100 solution in cyclohexane) N2H2 Solution (5% aq. solution) and hexanol (q.s.) was added to obtain RM-2. To the prepared reverse micellar solution of CuSO4 aqueous solution (2% w/v) (RM-1), another reverse micellar N2H2 Solution (5% aq. solution) (RM-2) was added dropwise with constant stirring maintaining the nitrogen atmosphere. In the presence of nitrogen atmosphere the resulting solution was allowed for further stirring for three hours to allow complete Ostwald ripening (particle growth). The nickel nanoparticles were extracted by adding absolute ethanol to the reverse micellar solution containing Cu-nanoparticles followed by centrifugation at 3000-4000 rpm for 10 min. By varying the water content parameter Wo (defined as the molar ratio of water to surfactant concentration, W0=[H20]/[surfactant] the size of the nanoparticles could be controlled. The sizes of the Cu-nanoparticles prepared at Wo=5 (the water content parameter Wo can be defined as the ratio of molar concentration of water to surfactant, Wo=[H20]/[surfactant] were confirmed as 14-18 nm through quasi elastic light scattering (QELS) data and transmission electron microscopy (TEM). The Cu-nanoparticles prepared were round in shape and brown in color (colloidal state). TEM photographs confirmed the sizes of copper nanoparticles used in experiment. Example-4: Procedure for the Cu-nanoparticles catalysed thiazolidine-2,4 dione derivative: In a round bottomed flask, a solution of thiazolidine-2,4-dione (10 mmol), amine (5 mol) and aldehyde (5 mmol) was prepared in a suitable solvent (10 ml) and the resulting mixture was stirred for few minutes. Copper nanoparticles (10 mol%, 600 μl) were added to the solution, and the reaction mixture was stirred at 50°C under N2 atmosphere for the appropriate reaction time. The progress of the reaction was monitored by thin layer chromatography. After the completion of the reaction, the reaction mixture was centrifuged (5000 rpm, 10 min) to pellet out the particles. The particles were then washed with absolute ethanol to remove all the organic impurities. These particles were reused for evaluating the performance in the next reaction. Structural assignments of the products are based on their H NMR, C NMR, elemental and Mass analysis. The analysis of complete spectral and compositional data revealed the formation of thiazolidine-2,4-dione derivatives. The metal nanoparticles work as an efficient catalyst for dehydration reactions, such as in Knoevenogel reaction and multi-component coupling reactions. The mild reaction conditions, medium to short reaction times, high to excellent yields, low cost and easy preparation and handling of the nanoparticles are the obvious advantages of the present method. Moreover, work-up is reduced to a filtration and evaporation of the solvent. Finally, these nanoparticles can be recovered by mild centrifugation and can be re-dispersed in the desired solvent and used again at least four times with negligible loss in its activity. WE CLAIM: 1. A process for conducting dehydration reaction using metal nanoparticles. 2. The process as claimed in claim 1, wherein said metal nanoparticles are selected from Nickel and copper nanoparticles, but are not limited to them. They might also include other transition metal catalysts. 3. The process as claimed in claim 1, wherein said metal nanoparticles below l00nm diameter and preferably between 10 to 20 nm are prepared using any chemical or physical method or a combination of them. 4. The process as in claim 1 relating to the preparation of nanoparticles in question with precise diameter and size distribution i.e., with high monodispersity (low polydispersity) using a method comprising the steps of: a) dissolving a surfactant in a solvent to obtain a surfactant solution, b) adding a metal salt followed by a co-surfactant to the surfactant solution to obtain an optically clear first reverse micellar solution (RM-1). c) adding a reducing agent to a surfactant solution to obtain a second reverse micellar solution (RM-2); d) mixing the reverse micellar solutions RM-1 and RM-2 to form metal nanoparticles; e) separating the nanoparticles from the micelles, washing and drying to obtain the pure nanoparticles. 5. The process as claimed in claim 3, wherein the surfactant is selected from cationic, anionic and non-ionic type. 6. The process as claimed in claim 3, wherein the solvent used for the formation of reverse micelles is a hydrocarbon such as a saturated straight chain or branched C6 to C10 hydrocarbon. 7. The process as claimed in claim 5, wherein the solvent used is n-hexane. 8. The process as claimed in claim 3, wherein the co-surfactant is a long chain alcohol selected from butanol to octanol. 9. The process as claimed in claim 3, wherein the surfactant is dissolved in the solvent to form a 0.08 to 0.15 M solution. 10. The process as claimed in claim 3, wherein the metal salt is selected from nickel nitrate, copper sulphate. 11. The process as claimed in claim 3, wherein the reducing agent is sodium borohydride and diazine. 12. The process as claimed in claim 3, wherein a 3 to 6% w/v solution of the reducing agent is used. 13. The process for conducting dehydration reaction, as claimed in claims 1 and 2, comprising the steps of adding Ni-nanoparticles to a mixture of carbonyl compound and an active methylene compound, stirring the reaction mixture thus obtained, followed by diluting the reaction mixture, and drying the organic layer to obtain the condensation product. 14. The process as claimed in claim 12, wherein said carbonyl compound and active methylene compound are used in a proportion of 1:1 by weight, with a slight excess of the active methylene compound. 15. The process as claimed in claim 12, wherein the reaction is conducted at 20 to 30°C, preferably, at 25°C. 16. The process as claimed in claim 12, wherein the reaction time is about 1 hour. 17. The process as claimed in claim 12, wherein said carbonyl compound is selected from ketones and aldehydes. 18. The process as claimed in claim 16, wherein said aldehyde is selected from the group of aliphatic aldehydes and aromatic aldehydes such as benzaldehyde and its derivatives such as chlorobenzaldehydes,nitrobenzaldehydes, hydroxybenzaldehydes, anisaldedehydes and any combination of the substituents. 19. The process as claimed in claim 12, wherein said active methylene compounds are selected from malonic acid, ethyl cyanoacetate, malononitrile, dimedone and the like. 20. The process as claimed in claim 12, wherein the Ni nanoparticle has a particle size of 15 to 20 nm. 21. The process as claimed in claim 12, wherein said Ni- nanoparticle is used in a proportion of about 10 mol%. 22. The process as claimed in claim 12, wherein the reaction mixture is diluted with a polar solvent. 23. The process for conducting dehydration reaction, as claimed in claims 1 and 2, to obtain thiazolidine-2,4-dione derivatives, comprising the steps of adding Cu-nanoparticles to a mixture of an aldehyde, thiazolidine-2,4-dione and an amine compound, followed by stirring, the reaction mixture, washing and drying the reaction mixture to obtain the condensation product, thiazolidine-2,4-dione derivatives. 24. The process as claimed in claim 22, wherein the reaction is conducted at a temperature in the range of 45 to 55°C, preferably at about 50°C. 25. The process as claimed in claim 22, wherein the reaction time is about 1 hour. 26. The process as claimed in claim 22, wherein said aldehyde is selected from aromatic aldehydes such as benzaldehyde and derivatives such as chlorobenzaldehydes, nitrobenzaldehydes, hydroxybenzaldehydes, anisaldehydes and any combination of the substituents. 27. The process as claimed in claim 22, wherein said amine compound is selected from aromatic amine such as aniline and substituted anilines, where the substituents are selected from methyl, methoxy,benzene diazo and the like. 28. The process as claimed in claim 22, wherein said aldehyde, thiazolidine-2,4-dione and amine are used in a molar proportion of aldehyde: thiazolidine-2,4-dione:amine ::1: 2:1. 29. The process as claimed in claim 22, wherein said copper nanoparticles are used in a proportion of about 10 mol%. 30. The process as claimed in claim 22, wherein said copper nanoparticles have a particle size of about 10 to 25 nm, preferably 14 to 18 nm. 31. The process as claimed in claim 22, wherein the solvent used in the reaction is a protic solvent, such as methanol, ethanol, polyethylene glycol and the like. This invention relates to a process for conducting dehydration reactions using metal nanoparticles. The nanoparticels are copper or nickel nanoparticles which are prepared in a reverse micellar system. The metal nanoparticles are used to catalyse dehydration reactions such as in Knovenagel condensation or in multi-component coupling reactions.

Documents:

272-KOL-2009-(08-03-2013)-CORRESPONDENCE.pdf

272-KOL-2009-(08-03-2013)-FORM-1.pdf

272-KOL-2009-(08-03-2013)-PA.pdf

272-KOL-2009-(16-10-2014)-CORRESPONDENCE.pdf

272-KOL-2009-(27-06-2012)-ABSTRACT.pdf

272-KOL-2009-(27-06-2012)-AMANDED CLAIMS.pdf

272-KOL-2009-(27-06-2012)-DESCRIPTION (COMPLETE).pdf

272-KOL-2009-(27-06-2012)-EXAMINATION REPORT REPLY RECEIVED.pdf

272-KOL-2009-(27-06-2012)-FORM-1.pdf

272-KOL-2009-(27-06-2012)-FORM-2.pdf

272-KOL-2009-(27-06-2012)-OTHERS.pdf

272-kol-2009-abstract.pdf

272-kol-2009-claims.pdf

272-kol-2009-correspondence.pdf

272-kol-2009-description (complete).pdf

272-kol-2009-form 1.pdf

272-kol-2009-form 2.pdf

272-kol-2009-form 3.pdf

272-kol-2009-form 5.pdf

272-kol-2009-specification.pdf