Title of Invention

"A PROCESS FOR THE PREPARATION OF α- BROMOKETONES"

Abstract

A process for the preparation of a- bromoketones The present invention relates to an improved process for preparation of α-bromoketones. The present invention particularly relates to an improved process for the α - bromination of sulphonamide substituted aryl-alkyl ketones ,which gives α -bromoketones. The invention comprises the reaction of sulphonamide substituted aryl-alkyl ketone and hydrobromic acid in dichloroethane in the presence of clay supported ammonium nitrate or other metal nitrates at the temperature of -5 to 400 C for a period of 10 to 24 hrs to obtain the product.

Full Text

The present invention relates to an improved process for preparation of oc-bromoketones. The present invention particularly relates to an improved process for the α- bromination of sulphonamide substituted aryl-alkyl ketones ,which gives a-bromoketones. α-Bromoketones are useful in the heterocyclic chemistry and particularly in pharmaceutical and dyes industry. The present process is useful for the preparation of a variety of a -bromoketones. The main aim of the invention is to prepare sulphonamide substituted α-bromoketones using aqueous hydrobromic acid and solid supported nitrate salts in chloro-hydrocarbon solvent. Further aim of the process is to avoid the use of corrosive molecular bromine. The important feature of the invention is that the reaction carried out in biphasic medium, which avoids the formation of nuclear bromination and product separation, is very easy. Moreover, the process gives only sulphonamide-substitutedα -bromoketones in high yield. Reference may be made to Tetrahedron Leetter 39, 4989 (1998) wherein molecular bromine and sulphuric acid converts ketones into dibromo product, which is further debrominated with diethylphosphite. This process has drawback of using molecular bromine & additional steps are involved. Another reference may be made to Bioorganic & Med.Chem. 9, 425 (1999) wherein, molecular bromine is used in the presence of aluminum chloride in ether. In this particular process, the use of both bromine and aluminum chloride required great precaution. Yet another reference may be made to Bull.Soc.Chim.Fr. 2360, (1961) wherein hydrobromic acid is used in the presence of sodium hypochloride .The main disadvantage of this procedure is that the preparation sodium hypochloride requires great precaution Yet another reference may be made to Chem.pharm. Bull.30 (11)4092 (1982), wherein molecular bromine is used in acetic acid. This particular procedure have drawback of using corrosive bromine and product isolation is difficult. All these procedures are based on the use of molecular bromine in combination with other reagents, which produces lot of waste at the source, and handling of bromine is difficult. Moreover, isolation of product is difficult from large quantity of aqueous medium, which result in low yield, and steps involved are more. Although practicable in laboratory, all these methods have little feasibility on commercial scale in terms of cost, handling of reagents, waste effluent and environmental consciousness. Therefore existing methods for the preparation of a-bromoketones have following disadvantages. 1. Molecular bromine is used which is very corrosive and produce waste at the source, which needs effluent treatment. 2. It is very difficult to handle molecular bromine. 3. Preparation of oxidizing reagent like NaOCl required great precautions. 4. Recovery of product from large aqueous medium is difficult. 5. Some of the method involves additional steps. 6. Metal halides used are corrosive. 7. At higher temperatures ring bromination occurs. The main object of the present invention is to provide a process for the preparation of α- bromoketones process using aqueous HBr and solid supported reagents, which avoids the drawbacks as detailed. Another object of the present invention is to develop a process for α-bromination of sulphonamide substituted aryl-alkyl ketones without the use of molecular bromine. The object of the invention is to avoid the use of aqueous unstable oxidizing agents. Yet another object of the invention is to use inexpensive hydrobromic acid and solid supported oxidizing reagent, which minimize the waste effluent in the large-scale preparation. This has positive influence on the economy of the process. In the drawing accompanying this specification Fig. 1 represents the a-bromination of sulphonamide substituted aryl-alkyl ketones. Accordingly, the invention provides a process for the preparation of α-bromoketones which comprises, sulphonamide substituted aryl-alkyl ketones of formula 1 wherein R is substitutent selected from ethoxy,methoxy,butoxy,propoxy,iso propoxy,chloro,bromo,iodo,nitro,amido,cyno ,the value of n is 1 to 3 dissolved in chloro hydrocarbon solvent is reacted with aqueous hydrobromic acid in the concentration of 25 to 48%, in the presence of metal selected from iron, copper or ammonium nitrates at the temperature range of-5 to 40°C for a period of 10 to 30 hrs to get α- bromoketones. (Formula Removed) In an embodiment of the present invention the R substituent used may be such as ethoxy, methoxy, butoxy, propoxy, iso propoxy, chloro, bromo, iodo, nitro, amido, cyno. In another embodiment of the invention, the n may be 1,2,3. Yet another embodiment of the present invention is that the concentration of hydrobromic acid used may be 25 to 48%. Still another embodiment of the invention, the organic solvent used may be selected from chloro-hydrocarbons like dichloromethane, dichloroethane, tetrachloroethane, chloroform. Yet another embodiment of the invention, the nitrate salts used may be selected from copper, iron, and non-metallic ammonium nitrate. In the drawing accompanying this specification Fig. 1 represents the a-bromination of sulphonamide substituted aryl-alkyl ketones. The invention comprises the reaction of sulphonamide substituted aryl-alkyl ketone and hydrobromic acid in dichloromethane in the presence of clay supported ammonium nitrate or other metal nitrates at the temperature of-5 to 40°C for a period of 10 to 24 hrs and receiving the product of general formula 1 To overcome with the difficulties associated with the a-bromination of ketones, the inventors of present invention have disclosed the process for the a-bromination of sulphonamide substituted aryl-alkyl ketones using aqueous hydrobromic acid in the presence of nitrate salts. The bromination ?>ccurs selectively a- to keto group and the yield are very high. The present inventors found that if the sulphonamide group is present in the ring, the bromination occurs in the side chain and not in benzene nucleus. Example-1 -a-Bromination of Ketones using Aq. HBr &clay supported ammonium nitrate 3-propionyl-5-methyl benzene sulphonamide (0.1 mol) is dissolved in dichloromethane (60 ml) and aqueous hydrobromic acid (40 %, 0.2 mol) is added to it at 25 °C. Then, clay supported ammonium nitrate (clayan, 0.2 mol) is added in portions while stirring and cooling the mixture. After 24 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives 3-(2-bromo-propionyl)-5-chlorobenzenesulphonamide in 80% yield. Example-2 a-Bromination of ketones using Aq. HBr & Clay supported copper(II) nitrate 3-propionyl-5-bromo benzene sulphonamide (o.l mol) is dissolved in dichloromethane (60 ml) and aqueous hydrobromic acid(40 %, o.2 mol) is added to it at25 °C. Then, clay supported copper (Il)nitreate (,0.2 mol) is added in portions while stirring and cooling the mixture. After 30 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives 3-(2-bromo-propionyl)-5-chlorobenzenesulphonamide in 76%yield. Example -3 a-Bromination of ketones using Aq. HBr & Clay supported ferric nitrate 3-propionyl-5-chlorobenzene sulphonamide (o.l mol) is dissolved in dichloromethane (60 ml) cooled to 25 °C and aqueous hydrobromic acid(40 %, o.2 mol) is added to it. Then, clay supported copper (Il)nitreate (,0.2 mol) is added in portions while stirring and cooling the mixture. After 28 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives 3-(2-bromo-propionyl)-5-chlorobenzenesulphonamide in 75% yield. Example 4 a-Bromination of Ketones using Aq. HBr &clay supported ammonium nitrate alkyl substituted 3-Acetyl sulphonamide (0.11 mol) is dissolved in 1,2 dichloro ethane (60 ml) and aqueous hydrobromic acid (40 %, 0.2 mol) is added to it at 25 °C. Then, clay supported ammonium nitrate (clayan, 0.25 mol) is added in portions while stirring and cooling the mixture. After 24 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives substituted (2-bromo-acetophenyl)-l-benzenesulphonamide in 90% yield. Example-5 a-Bromination of ketones using Aq. HBr & Clay supported copper(II) nitrate methoxy substituted 3-Acetophenone sulphonamide (0.3 mol) is dissolved in 1,2 dichloroethane (200 ml) at 25 °C, and aqueous hydrobromic acid(40 %, 0.7 mol) is added to it. Then, clay supported copper (II) nitrate (,0.5 mol) is added in portions while stirring and cooling the mixture. After 30 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives 3-(2-bromo-propionyl)-5- chlorobenzenesulphonamide in 76%yield. Example -6 a-Bromination of ketones using Aq. HBr & Clay supported ferric nitrate Chloro substituted 3-Acetophenone sulphonamide (0.05 mol) is dissolved in chloroform (20 ml) and aqueous hydrobromic acid(40 %, o.l mol) is added to it at 10 °C. Then, clay supported copper (II) nitrate (0.2 mol) is added in portions while stirring and cooling the mixture. After 28 hrs, it is filtered, washed with more dichloromethane. Evaporation of solvent gives (2-bromo-acetophenyl)-l-benzenesulphonamide in 75% yield. We Claim: 1. A process for the preparation of α- bromoketones. Which comprises, sulphonamide substituted aryl-alkyl ketones of formula 1 wherein R is substitutent selected from ethoxy,methoxy,butoxy,propoxy,iso propoxy,chloro,bromo,iodo,nitro,amido,cyno ,the value of n is 1 to 3 dissolved in chloro hydrocarbon solvent is reacted with aqueous hydrobromic acid in the concentration of 25 to 48%, in the presence of metal selected from iron, copper or ammonium nitrates at the temperature range of-5 to 40°C for a period of 10 to 30 hrs to get a- bromoketones. (Formula Removed) 2. A process as claimed in claim 1, wherein the bromination is carried out in chloro hydrocarbon solvent selected from dichloromthane,dichloroethane,chloroform,tetrachloroethane or solevent free condition. 3. A process as claimed in claim 1, wherein the process is suitable for all aryl-alkyl ketones having sulphonamide as one of the substituent in benzene nucleus along with other substituent like, alkoxy and halogen. 4. The process as claimed in claim 1 to 3 has the feature that it is suitable for aryl-alkyl ketone bearing electron-withdrawing substituents on the benzene nucleus. 5. The process claimed in claims 1 to 4 has the feature that the maximum bromination occurs at the temperature range of -5 to 40 C. 6. The process claimed in claims 1 to 5 has the feature that the aqueous hydrobromic acid used may be in the concentration of 25 to 48%. 7. The process claimed in claims 1 to 5 has the feature that all the chloro hydrocarbons. 8. A process for the preparation of a- bromoketones substantially as herein described with reference to the examples and drawing accompanying the specification.

Documents:

259-DEL-2003-Abstract-(24-09-2008).pdf

259-del-2003-abstract.pdf

259-DEL-2003-Claims-(24-09-2008).pdf

259-del-2003-claims.pdf

259-del-2003-complete specification(granted).pdf

259-DEL-2003-Correspondence-Others-(24-09-2008).pdf

259-del-2003-correspondence-others.pdf

259-del-2003-correspondence-po.pdf

259-DEL-2003-Description (Complete)-24-09-2008.pdf

259-del-2003-description (complete).pdf

259-del-2003-drawings.pdf

259-del-2003-form-1.pdf

259-del-2003-form-18.pdf

259-DEL-2003-Form-2-(24-09-2008).pdf

259-del-2003-form-2.pdf

259-DEL-2003-Form-3-(24-09-2008).pdf

259-del-2003-form-3.pdf