Process for carbonylating phenylalkyl derivatives by means of carbon monoxide

Abstract

The invention is directed a process of preparing a compound of formula (I), wherein R 1 , R 2 , R 3 and z are as defined herein.

1 . A process for preparing a compound of formula I  
     
       
         
         
             
             
         
       
       wherein:  
       R1 and R2 are each independently —(C 1 -C 4 )-alkyl;  
       R3 is —C(O)—(C 1 -C 4 )-alkyl, which is monosubstituted by Cl or Br, or —C(O)—(C 3 -C 10 )-cycloalkyl; and  
       Z is hydrogen or —(C 1 -C 10 )-alkyl;  
       comprising reacting a compound of formula II  
       
         
           
           
               
               
           
         
       
       wherein:  
       R1 and R3 are each as defined in formula I;  
       X is Cl, Br or —OH; and  
       R4 is R2 or together with X form ═CH 2  or ═CH—(Cl—C 3 )-alkyl;  
       with carbon monoxide or a carbon monoxide-releasing compound in the presence of concentrated sulfuric acid, hydrogen fluoride or a superacid or mixtures thereof, and then  
       a) adding water to give the compound of formula I wherein Z is hydrogen, or  
       b) adding (C 1 -C 10 )-alkyl-OH when X is Cl or Br, or R4 together with X form ═CH 2  or ═CH—(C 1 -C 3 )-alkyl, to give the compound of formula I wherein Z is —(C 1 -C 10 )-alkyl.  
     
   
   
       2 . The process according to  claim 1  for preparing the compound of formula I, wherein 
 R1 and R2 are both methyl,    R3 is —C(O)-propyl monosubstituted by Cl, or —C(O)-cyclopropyl; and    Z is hydrogen or —(C 1 -C 4 )-alkyl.    
   
   
       3 . The process according to  claim 1 , wherein the carbon monoxide-releasing compound is selected from the group of formic acid, a formate salt with an inorganic or organic cation or metal carbonyl, or a mixture thereof.  
   
   
       4 . The process according to  claim 1 , wherein the superacid used is an acid from the group of perchloric acid, chlorosulfonic acid, fluorosulfonic acid, trifluoromethanesulfonic acid, perfluorobutane-1-sulfonic acid, Lewis acid or a conjugated protic acid-Lewis acid complex.  
   
   
       5 . The process according to  claim 4 , wherein the Lewis acid is SO 3 , aluminum trichloride, or antimony pentafluoride.  
   
   
       6 . The process according to  claim 4 , wherein the conjugated protic acid-Lewis acid complex is sulfuric acid and SO 3  complex, sulfuric acid and boric acid complex, fluorosulfonic acid and antimony pentafluoride complex, trifluoromethanesulfonic acid and antimony pentafluoride complex, hydrogen fluoride and antimony pentafluoride complex, HF and TaF 5  complex, BF 3  and HF complex, BF 3  and H 3 PO 4  complex, fluorosulfonic acid and SO 3  complex, HSO 3 F, HF and SbF 5 , complex, or HSO 3 F, SO 3  and SbF 5 .  
   
   
       7 . The process according to  claim 1 , wherein the superacid is an immobilized superacid.  
   
   
       8 . The process according to  claim 7 , wherein the immobilized superacid is immobilized trifluoromethanesulfonic acid or fluorosulfonic acid.  
   
   
       9 . The process according to  claim 1 , wherein the process is carried out in the presence of a solvents selected from liquid sulfur dioxide, supercritical carbon dioxide, sulfolane, n-alkanes having from 4 to 12 carbon atoms, chlorobenzene, fluorobenzene, toluene, cumene, halogenated hydrocarbons, methyl acetate, ethyl acetate or n-butyl acetate.  
   
   
       10 . The process according to  claim 1 , wherein the process is carried out in the presence of an additive which is converted rapidly under contact with carbon monoxide to metal carbonyls.  
   
   
       11 . The process according to  claim 10 , wherein the additive is copper(l) oxide, silver(l) oxide, silver nitrate, iron pentacarbonyl Fe(CO) 5 , disodium tetracarbonylferrate(−2) Na 2 Fe(CO) 4 , octacarbonyidicobalt(O) Co 2 (CO) 8  or nickel tetracarbonyl Ni(CO) 4 .  
   
   
       12 . The process according to  claim 1 , wherein the process is carried out at a CO pressure of from 1 bar to 500 bar, or at a reaction temperature of from −70° C. to +100° C.  
   
   
       13 . The process according to  claim 1 , wherein from 0.1 mol to 5.0 mol of the compound of the formula II are used per liter of superacid, in particular from 0.3 mol to 3.0 mol.  
   
   
       14 . The process according to  claim 10 , wherein the additive is used in an amount of from 5 mol % to 100 mol % based on the compound of formula II.  
   
   
       15 . The process according to  claim 1 , wherein the compound of formula II is reacted with carbon monoxide or a carbon monoxide-releasing compound in the presence of water, water being present in an amount of from 2 mol % to 800 mol % based on the compound of the formula II, and of concentrated sulfuric acid or hydrogen fluoride or of a superacid or mixtures thereof.  
   
   
       16 . The process according to  claim 15 , wherein the compound of formula II where X is bromine, R1 is methyl, R2 is methyl and R3 is 4-chlorobutyryl is reacted with carbon monoxide in the presence of trifluoromethanesulfonic acid and water, water being present in an amount of from 50 mol % to 500 mol % based on the compound of the formula II.  
   
   
       17 . The process according to  claim 16 , wherein water is used in an amount of from 90 mol % to 300 mol %, in particular about 200 mol %, based on the compound of formula II.  
   
   
       18 . A compound of formula X  
     
       
         
         
             
             
         
       
       wherein Y is chlorine or bromine, and  
       R1 and R5 are each independently —(C 1 -C 4 )-alkyl.  
     
   
   
       19 . The compound according to  claim 18 , wherein 
 Y is a chlorine atom and R1 and R5 are each methyl.    
   
   
       20 . A process for preparing the compound according to  claim 18 , comprising 
 a) reacting a compound of formula III                          wherein Y is chlorine or bromine, and R1 and R4 are each independently —(C 1 -C 4 )-alkyl,    with oxygen in the presence of cobalt(II) acetate tetrahydrate and N-hydroxyphthalimide, or    b) reacting a compound of formula XI                          wherein Y is hydrogen, chlorine or bromine,    X is chlorine or bromine,    R1 and R4 are each independently —(C 1 -C 4 )-alkyl or R4 and X together form ═CH 2  or ═CH—(C 1 -C 3 )-alkyl; with water.    
   
   
       21 . A process for preparing a compound of formula VIII  
     
       
         
         
             
             
         
       
       wherein Y is hydrogen, chlorine or bromine, and R1 and R4 are each independently —(C 1 -C 4 )-alkyl,  
       comprising illuminating a compound of formula III  
       
         
           
           
               
               
           
         
       
       in the presence of N-bromosuccinimide or 1,3-dibromo-5,5-dimethylhydantoin and with heating.  
     
   
   
       22 . The process according to  claim 21 , wherein the compound of the formula III is used wherein Y is chlorine, and R1 and R4 are each methyl.  
   
   
       23 . A process for preparing a compound of formula VIII  
     
       
         
         
             
             
         
       
       wherein Y is hydrogen, chlorine or bromine, and R1 and R4 are each independently —(C 1 -C 4 )-alkyl,  
       comprising illuminating a compound of formula III  
       
         
           
           
               
               
           
         
       
       in an aqueous biphasic mixture, wherein the aqueous phase comprises a bromine salt and the other phase is a liquid which is insoluble or only sparingly soluble in water.  
     
   
   
       24 . The process according to  claim 23 , wherein the aqueous biphasic mixture consists of water and dichloromethane, and sodium bromate is present in the aqueous phase.  
   
   
       25 . The process according to  claim 23 , wherein HBr is metered into the aqueous phase.  
   
   
       26 . A process for preparing a compound of formula IX  
     
       
         
         
             
             
         
       
       wherein Y is hydrogen, chlorine or bromine, and R1 and R4 are each independently —(C 1 -C 4 )-alkyl,  
       comprising reacting a compound of formula III  
       
         
           
           
               
               
           
         
       
       wherein Y is hydrogen, chlorine or bromine, and R1 and R4 are each independently —(C 1 -C 4 )-alkyl, to give a compound of formula IIIa  
       
         
           
           
               
               
           
         
       
       free-radically chlorinating the compound of formula IIIa at the benzylic position, with sulfuryl chloride or tert-butyl hypochlorite to give the compound of the formula IX.  
     
   
   
       27 . The process according to  claim 26 , wherein the compound of the formula III is used wherein Y is chlorine atom, and R1 and R4 are each methyl.