Process for the preparation of a polyunsaturated ketone compound

Abstract

A process for the preparation of a polyunsaturated thiol comprising: (1) reacting a polyunsaturated alcohol in the presence of a compound of formula R 2 —SO 2 Hal wherein R 2 is a C 1-20 hydrocarbyl group, such an C 1-10 alkyl group, to form a polyunsaturated sulphonyl ester; (2) converting the polyunsaturated sulphonyl ester to a polyunsaturated thioester by reacting with an anion of formula − SC(═O)R 4 wherein R 4 is a C 1-20 hydrocarbyl group; (3) converting the polyunsaturated thioester to form a polyunsaturated thiol optionally in the presence of an antioxidant, e.g. using a metal carbonate. (4) reacting said polyunsaturated thiol with a compound (LG)R 3 COX wherein X is an electron withdrawing A group and R 3 is an alkylene group carrying a leaving group (LG), such as LG-CH 2 — forming (I) where X is an electron withdrawing group and LG is a leaving group; optionally in the presence of an antioxidant, so as to form a polyunsaturated ketone compound.

1 - 14 . (canceled) 
     
     
         15 . A process for the preparation of a polyunsaturated thiol comprising:
 (1) reacting a polyunsaturated alcohol in the presence of a compound of formula R 2 —SO 2 Hal, wherein R 2  is a C 1-20  hydrocarbyl group to form a polyunsaturated sulphonyl ester;   (2) converting the polyunsaturated sulphonyl ester to a polyunsaturated thioester by reacting with an anion of formula  − SC(═O)R 4  wherein R 4  is a C 1-20  hydrocarbyl group; and   (3) converting the polyunsaturated thioester to form a polyunsaturated thiol optionally in the presence of an antioxidant.   
     
     
         16 . The process as claimed in  claim 15  comprising:
 (1) reacting a polyunsaturated alcohol of formula (I) or (I′):
   R—OH or R′—OH  (I) or (I′),
 
 
 wherein R is an optionally substituted C 9-23  unsaturated hydrocarbon group optionally interrupted by one or more heteroatoms or groups of heteroatoms selected from S, O, N, SO, SO 2 , said hydrocarbon group comprising at least 2 double bonds; and 
 wherein R′ is a linear, unsubstituted C 9-23  unsaturated hydrocarbon group, said hydrocarbon group comprising at least 2 double bonds; 
 in the presence of a compound of formula R 2 —SO 2 Hal wherein R 2  is a C 1-20  hydrocarbyl group to form a polyunsaturated sulphonyl ester compound of formula (V) or (V′):
   R—OSO 2 R 2  or R′OSO 2 R 2   (V) or (V′);
 
 
 (2) converting the polyunsaturated sulphonyl ester (V) or (V′) to a polyunsaturated thioester by reacting with an anion of formula  − SC(═O)R 4 , wherein R 4  is a C 1-20  hydrocarbyl group to form a polyunsaturated thioester compound of formula (VI) or (VI′):
   R—SCOR 4  or R′—SCOR 4   (VI) or (VI′),
 
 wherein R and R′ are as hereinbefore defined; and 
 
 (3) converting the polyunsaturated thioester optionally in the presence of an antioxidant and optionally in the presence of a metal carbonate to form a polyunsaturated thiol compound of formula (VII) or (VII′):
   R—SH or R′—SH  (VII) or (VII′),
 
 wherein R and R′ are as hereinbefore defined. 
 
 
     
     
         17 . The process as claimed in  claim 16  comprising at least the following steps:
 (1) reacting (3Z,6Z,9Z,12Z, 15Z)-octadeca-3,6,9,12,15-pentaen-1-ol 
 
       
         
           
           
               
               
           
         
         or (2E,6Z,9Z,12Z, 15Z,)-octadeca-2,6,9,12,15-pentaen-1-ol; 
       
       
         
           
           
               
               
           
         
         with methanesulphonyl chloride in the presence of a base so as to form a 
       
       
         
           
           
               
               
           
         
         (2) reacting the reaction product of step (1) with a thioacetate ion to form a thioester of formula: 
       
       
         
           
           
               
               
           
         
       
       and
 (3) reacting the product of step (2) with potassium carbonate in the presence of an antioxidant to form a thiol of formula: 
 
       
         
           
           
               
               
           
         
       
     
     
         18 . The process as claimed in  claim 15  wherein R is a C 11-19  linear unsubstituted carbon chain comprising at least 4 non conjugated double bonds. 
     
     
         19 . The process as claimed in  claim 15  wherein the polyunsaturated alcohol R—OH or R′—OH is obtained by reduction of its corresponding aldehyde R 1 CHO or R 1 ,CHO in the presence of an electrophilic reducing agent:
 wherein R 1  is an optionally substituted C 9-23  unsaturated hydrocarbon group optionally interrupted by one or more heteroatoms or groups of heteroatoms selected from S, O, N, SO, SO 2 , said hydrocarbon group comprising at least 2 double bonds in which a terminal —CH 2 — link is removed (e.g. a C 10-18  linear unsubstituted carbon chain comprising at least 4 non conjugated double bonds); and 
 R 1′  is a linear, unsubstituted C 9-23  unsaturated hydrocarbon group, said hydrocarbon group comprising at least 2 double bonds in which a terminal —CH 2 — link is removed (e.g. a C 10-18  linear unsubstituted carbon chain comprising at least 4 non conjugated double bonds). 
 
     
     
         20 . The process as claimed in  claim 15  wherein the sulphonyl halide is a C 1-4  alkylsulphonyl chloride. 
     
     
         21 . The process as claimed in  claim 15  wherein the reaction with the sulphonyl halide takes place in the presence of a base. 
     
     
         22 . The process as claimed in  claim 15  wherein R 4  is a C 1-4  alkyl so as to form a thioacetate anion. 
     
     
         23 . The process as claimed in  claim 15  wherein the thiol formation takes place in the presence of a metal carbonate. 
     
     
         24 . The process as claimed in  claim 15  wherein an antioxidant is present in step (3) and the antioxidant is butyl hydroxyanisole, butyl hydroxytoluene, propyl gallate, tocopherol, ascorbic acid, ascorbyl palmitate, thioglycerol, thioglycolic acid, sodium bisulphite, sodium sulphite, sodium metabisulphite, edetate tetrasodium, or EDTA. 
     
     
         25 . The process as claimed in  claim 24  wherein the antioxidant is tocopherol. 
     
     
         26 . The process as claimed in  claim 15  in which the product is purified using normal or reversed phase column chromatography. 
     
     
         27 . The process as claimed in  claim 15  in which the polyunsaturated alcohol is purified using normal or reversed phase column chromatography. 
     
     
         28 . The process as claimed in  claim 15  comprising: 
       
         
           
           
               
               
           
         
       
     
     
         29 . The process as claimed in  claim 15  wherein R 2  is a C 1-10  alkyl group. 
     
     
         30 . The process as claimed in  claim 19  wherein the electrophilic reducing agent is DIBAH (diisobutylaluminum hydride). 
     
     
         31 . The process as claimed in  claim 20  wherein the sulphonyl halide is methanesulphonyl chloride. 
     
     
         32 . The process as claimed in  claim 21  wherein the base is an amine. 
     
     
         33 . The process as claimed in  claim 22  wherein R 4  is methyl. 
     
     
         34 . The process as claimed in  claim 33  wherein R 4  is methyl so as to form potassium thioacetate. 
     
     
         35 . The process as claimed in  claim 23  wherein the thiol formation takes place in the presence of potassium carbonate. 
     
     
         36 . The process as claimed in  claim 25  wherein the antioxidant is α-tocopherol.