Title of Invention	"IMPROVED PROCESS FOR PRODUCING CYANOPIPERIDINE"
Abstract	The present invention relates to an improved and single step process for producing cyanopiperidine by dehydrating respective piperidine carboxamide employing a suitable dehydrating agent.

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FIELD OF THE INVENTION This invention, in general relates to a process for producing cyanopiperidine. More specifically, but without restriction to the particular embodiments hereinafter described in accordance with the best mode of practice, this invention relates to an improved single step process for producing cyanopiperidine by dehydrating respective piperidine carboxamide employing a suitable dehydrating agent. BACKGROUND OF THE INVENTION Cyanopiperidines, especially 4-cyanopiperidine, are used as intermediates for the production of pharmacologically valuable substances like antidepressants, anti-inflammatory and immunomodulators. 4-Cyanopiperidine.is.also used as a starting material for the preparation of a large number of piperidine derivatives. The prior art discloses different conventional chemistry for producing cyanopiperidines. U. S. Patent 5,869,663 to Emonds-Alt et al, discloses a single step process for producing 4-cyanopiperidine from isonipecotamide (or piperidine-4-carboxamide) by dehydrating with phosphorous oxychloride, addition of concentrated mass to maintain gH-13, followed by multiple extractions,with dichloromethane and ether. This process is laborious and is not commercially lucrative due to the involvement of multiple extractions with a mixture of low boiling solvents and generation of a lot of effluents. Moreover, the yield with above process is very less (approx. 25% w/w, 30% molar). U. S. Patent 4,284,636 to Carr et al, discloses the preparation of.4-cyanopiperidine by reacting piperidine-4-carboxamide with triflouroacetic anhydride and refluxing the reaction mass for 19 hours. Trifluoroacetic anhydride and trifluoroacetic acid are removed in vacuum and residual 4-cyano-l-fluoroacetyl piperidine is added to aqueous solution of potassium carbonate and methanol. Methanol is recovered and benzene is added to the concentrated reaction mass. Workup and distillation in vacuum gives the desired product 23%, w/w and 27% molar yield of 4-cyanopiperidine. The major drawbacks of this process are that it involves several steps, usage of hazardous chemicals, multiple solvents, generation of effluents and lower yields, thus, rendering the process industrially unattractive. Therefore, there is a need to develop an improved process for producing cyanopiperidines, in particular 4-cyanopiperidine, which overcomes the disadvantages associated with the processes disclosed in the prior art. OBJECTS AND SUMMARY OF THE INVENTION It is, therefore, an object of the present invention to improve upon limitations in the prior art. These and other objects are attained in accordance with the present invention wherein there is provided several embodiments of an improved and single step process for producing cyanopiperidine by dehydrating respective piperidine carboxamide using a suitable dehydrating agent thionyl chloride to produce cyanopiperidine with higher yields and selectivity. In one preferred embodiment of the present invention, there is provided an improved process for producing 4-cyanopiperidine, wherein the process comprises treating piperidine-4-carboxamide with thionyl chloride, neutralizing the resultant reaction mass with caustic lye and extracting the desired product from the reaction mass using a suitable non-polar solvent. In another preferred embodiment of the present invention, there is provided an improved and single step process, wherein the process comprises dehydrating the piperidine-4-carboxamide by treating piperidine-4-carboxamide with thionyl chloride at a temperature of 10°-150°C, preferably 20°-100°C, to produce 4-cyanopiperidine, wherein the ratio of piperidine-4-carboxamide and thionyl chloride is 1:15 moles, preferably 1:80 moles. DETAILED DESCRIPTION OF THE INVENTION The present invention discloses an improved process for producing cyanopiperidine. The process disclosed in the present invention is advantageous over prior art processes because it involves a single step reaction, use of a single solvent and better yields and selectivity, by suppressing the formation of unwanted products. The disclosed piperidine-4-carboxamide used for the preparation of 4-cyanopiperidine is of high purity (M.p.-144-149°C) and moisture contents of less than 0.2-2% preferably 0.2-1.0%. The process disclosed in the present invention comprises treating piperidine-4-carboxamide with thionyl chloride in a ratio of 1:15 moles, preferably 1:80 moles, at a temperature of 10°-150°C, preferably 20°-100°C, for 4-6 hours, drying the resultant and adding 46% caustic lye to adjust pH 12-13, extracting the resultant alkaline mass with a suitable non-polar solvent at a temperature of 20°-25°C, separating the organic layer and distilling the concentrated mass through high vacuum, cooling the reaction mass to 30°-35°C, pouring into crushed ice and treating with excess of 46% caustic lye to adjust pH between 12 and 13. Alkaline reaction mass is extracted with suitable aromatic hydrocarbon solvents, like benzene, toluene and xylene etc. Organic layer is separated and concentrated to recover solvent. Concentrated mass thus obtained is distilled under vacuum to obtain pure 4-cyanopiperidine in 60-65% molar yield. The following examples are illustrative of the invention and should not be construed as limiting the scope of the invention in any manner. It is understood that the variation of the process described below are possible without departing from the scope and spirit of the invention. Example-1 Thionyl chloride 232 gm (molar ratio thionyl chloride: piperidine-4-carboxamide = 2.53:1) is taken in a 500 ml four-necked reaction flask, fitted with glass agitator and a condenser. A vent is provided at the condenser top passing through the 10% diluted solution of caustic lye to neutralise the vent gases. Piperidine-4-carboxamide 100 gm is added lot wise with continuous stirring over a period of 30 minutes, temperature increased from 32° to 65°C due to exothermicity of reaction. Reaction mixture is maintained at 65°-70°C for 3-4 hours and sample is drawn and analysed, 4-Cyanopiperidine 94.78% Area, Piperidine-4-carboxamide = Nil is obtained. Reaction mass is cooled to room temperature and poured over 400 gm crushed ice by maintaining temperature 0°-10°C, 160 gm (46% solution) caustic lye is added to the above mass while maintaining temperature between 15°-20°C, pH is adjusted between 12 and 13. Alkaline reaction mass is extracted with (400 ml x 4) toluene. The organic layer is separated and the solvent is recovered by atmospheric distillation. Concentrated mass is distilled under high vacuum (4-6 mm Hg) to obtain 52.5 gm (Molar yield=61%) 4-cyanopipeiridne with purity 99.75%. Example-2 Thionyl chloride 70 gm (molar ratio, thionyl chloride:piperidine-4-carboxamide (1.50:1) is taken in a 250 ml 4-necked glass reactor fitted with an agitator and a condenser. Vent is provided at condenser top, passing through the 10% diluted solution of caustic lye to neutralize the vent gases. Piperidine-4-carboxamide 50 gm is added lot wise and the same procedure as in Example-1 is followed. 27 gm (molar yield 62.8%) 4-cyanopipeiridine is obtained after final distillation with purity 99.0%. Example-3 Thionyl chloride 465 gm (molar ratio, thionyl chloride:piperidine-4-carboxamide 10:1) is taken in a 500 ml, 4-necked glass reactor fitted with an agitator and a condenser. Vent is provided at condenser top passing through the 10% diluted solution of caustic lye to neutralize the vent gases. Piperidine-4-carboxamide 48 gm is added lot-wise and after following the same procedure as in Example-1, 13.5 gm (molar yield 32.7%) of 4-cyanopiperidine is obtained with 98.75% purity. We Claim: 1. An improved process for producing cyanopiperidine characterized in that comprising dehydrating piperidine carboxamide by treating piperidine carboxamide with thionyl chloride to produce cyanopiperidine, neutralising the reaction mass obtained after dehydration and extracting the reaction product with an aromatic hydrocarbon solvent, distilling out the solvent and distilling the resultant to obtain cyanopiperidine, wherein the molar ratio of piperidine carboxamide to thionyl chloride is 1:15. 2. The process according to claim 1, wherein the aromatic hydrocarbon solvent is selected from benzene, toluene or xylene. 3. The process according to claim 1, wherein the molar ratio of piperidine carboxamide to thionyl chloride preferably 1:8, and most preferably 1:4. 4. The process according to claim 1, wherein the reaction takes place in a single step. 5. An improved process for producing cyanopiperidine as substantially herein described with reference to examples.

Documents:

2035-del-2004-abstract.pdf

2035-del-2004-claims.pdf

2035-del-2004-complete specification (granted).pdf

2035-del-2004-correspondence-others.pdf

2035-del-2004-correspondence-po.pdf

2035-del-2004-description (complete).pdf

2035-del-2004-form-1.pdf

2035-del-2004-form-2.pdf

2035-del-2004-form-26.pdf

2035-del-2004-form-3.pdf

2035-del-2004-form-5.pdf

2035-del-2004-petition-137.pdf