Process for the preparation of carboxylic acid esters

Abstract

There is provided a process for preparing a carboxylic acid ester of formula (3): R 2 COOR 1 (3) wherein R 1 is an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an aralkyl group which may be substituted, or a heteroarylalkyl group which may be substituted, and R 2 is an alkyl group which may be substituted, an alkenyl group which may be substituted, an alkynyl group which may be substituted, an aryl group which may be substituted, a heteroaryl which may be substituted, an aralkyl group which may be substituted, or a heteroarylalkyl group which may be substituted, which process is characterized by the steps of reacting a monohydroxy compound of formula (1): R 1 OH   (1) wherein R 1 is as defined above, with a zirconium compound of formula (6): Zr(OR 8 ) 4   (6) wherein R 8 is an alkyl group or an aryl group which may be substituted and is not the same as R 1 , to prepare a zirconium catalyst, and reacting a carboxylic acid of formula (2): R 2 COOH   (2) wherein R 2 is as defined above, with the monohydroxy compound of formula (1) in the presence of the zirconium catalyst.

1 . A process for preparing a carboxylic acid ester of formula (3):  
         R 2 COOR 1    (3)  
       wherein 
 R 1  is 
 an alkyl group which may be substituted,  
 an alkenyl group which may be substituted,  
 an alkynyl group which may be substituted,  
 an aralkyl group which may be substituted, or  
 a heteroarylalkyl group which may be substituted, and  
 
 R 2  is 
 an alkyl group which may be substituted,  
 an alkenyl group which may be substituted,  
 an alkynyl group which may be substituted,  
 an aryl group which may be substituted,  
 a heteroaryl which may be substituted,  
 an aralkyl group which may be substituted, or  
 a heteroarylalkyl group which may be substituted,  
 
 which process comprises the steps of  
 reacting a monohydroxy compound of formula (1):  
   R 1 OH   (1)  
 wherein R 1  is as defined above, with a zirconium compound of formula (6):  
   Zr(OR 8 ) 4    (6)  
 wherein R 8  is an alkyl group or an aryl group which may be substituted and is not the same as R 1 , to prepare a zirconium catalyst, and 
 reacting a carboxylic acid of formula (2):  
   R 2 COOH   (2)  
 
 wherein R 2  is as defined above, with the monohydroxy compound of formula (1) in the presence of the zirconium catalyst.  
 
     
     
         2 . A process according to  claim 1 , wherein the carboxylic acid of formula (2) is a cyclopropanecarboxylic acid compound of formula (4)  
       
         
           
           
               
               
           
         
       
       wherein, 
 R 3 , R 4 , R 5 , R 6  and R 7  each independently represents  
 a hydrogen atom, a halogen atom,  
 an alkyl group which may be substituted,  
 an alkenyl group which may be substituted,  
 an alkynyl group which may be substituted,  
 an aralkyl group which may be substituted,  
 an aryl group which may be substituted, or  
 a heteroaryl group which may be substituted,  
 and the resultant carboxylic acid ester is a cyclopropanecarboxylic acid ester of formula (5)  
                     
 wherein R 1 , R 3 , R 4 , R 5 , R 6  and R 7  are as defined.  
 
     
     
         3 . A process according to  claim 2 , wherein R 3 , R 4 , R 5 , R 6  and R 7  are the same or different and independently represent hydrogen, halogen, phenyl, methyl, ethyl, dimethoxymethyl, 1-propenyl, 2-methyl-1-propenyl, 3-methyl-2-butenyl, 2,2-dichlorovinyl, 2,2,2-trichloroethyl, 2-chloro-2-fluorovinyl, 2-bromovinyl, 2,2-dibromovinyl, 1,2,2,2-tetrabromoethyl, 1,2-dibromo-2,2,-dichloroethyl, 2-chloro-3,3,3-trifluoro- 1-propenyl, 3,3,3-trifluoro-2-(trifluoromethyl)-1-propenyl, 2-phenyl-1-propenyl, 2-phenylvinyl, 2-methyl-3-phenyl-2-butenyl, 2,2-difluorocyclopropylidene)methyl, 2-(tert-butoxycarbonyl)vinyl, 2-fluoro-2-(methoxycarbonyl)vinyl, 2-fluoro-2-(ethoxycarbonyl)vinyl, 2-fluoro-2-(tert-butoxycarbonyl)vinyl, 2-{2,2,2-trifluoro-1-(trifluoromethyl)ethoxycarbonyl}-vinyl, 2-aza-2-methoxyvinyl, 4-aza-4-methoxy-3-methylbuta-1,3-dienyl,2-{(tert-butyl)-sulfonyl}-2-(tert-butoxycarbonyl)vinyl, 2,2,2-tribromo-1-(methylsulfonyloxy)ethyl, or 2,2-dibromo-2-(hydroxysulfinyl)-1-(methoxy)ethyl.  
     
     
         4 . A process according to  claim 2 , wherein the cyclopropanecarboxylic acid compound of formula (4) is 2,2-dimethyl-3-(2,2-dichlorovinyl)cyclopropanecarboxylic acid, 2,2-dimethyl-3-(2-methyl-1-propenyl)cyclopropanecarboxylic acid, or 2,2-dimethyl-3-(1-propenyl)cyclopropanecarboxylic acid.  
     
     
         5 . A process according to  claim 1  or  3 , wherein the monohydroxy compound of formula (1) is a primary alcohol.  
     
     
         6 . A process according to  claim 2 , wherein the monohydroxy compound of formula (1) is a benzyl group which may be substituted.  
     
     
         7 . A process according to  claim 2  or  3 , wherein R 1  represents a C 7-20  aralkyl group which may be substituted with at least one member selected from the group consisting of 
 a halogen atom, and    C 1-14  alkyl, phenyl, phenoxy, C 1-4  alkoxy and C 2-4  alkoxyalkyl groups which may be substituted with a halogen atom,    a propargyl group, a cyano group, a nitro group, and a C 3  haloacyloxy-methyl group.    
     
     
         8 . A process according to  claim 7 , wherein R 1  is a benzyl group which may be substituted with at least one member selected from the group consisting of a halogen atom, a methyl group, a phenyl group, a phenoxy group, a halo-phenoxy group, a propargyl group, a halomethyl, a halomethoxy group, a cyano group, nitro, a methoxymethyl group and a halogen-substituted methoxymethyl group.  
     
     
         9 . A process according to  claim 2 ,  3  or  4 , wherein the monohydroxy compound of formula (1) is 
 4-(2-thienyl)indan-2-ol,    (2,3,6-trifluoro-4-pyridyl)methane-1-ol,    (1-prop-2-ynyl-2-methylindole-3-yl)methane-1-ol, { 1-prop-2-ynyl-2-(trifluoromethyl)indole-3-yl}methane-1-ol,    2-furylmethyl alcohol, 3-furylmethyl alcohol, (5-phenoxy-3-furyl)methyl alcohol, (5-benzyl-3-furyl)methane-1-ol, {5-(difluoromethyl)-3-furyl}methane 1-ol, 5-propargylfurfuryl alcohol, (5-methylisoxazol-3-yl)methane-1-ol, 1-{2-(trifluoromethyl)-1,3-thiazol-4-yl}prop-2-yne-1-ol, 1- {2-(trifluoromethoxy)-1 ,3-thiazol-4-yl}prop-2-yne-1-ol, 1-{1-prop-2-ynyl-5-(trifluoromethyl)pyrrole-3-yl}prop-2-yne-1-ol, (1-prop-2-ynylpyrrole-3-yl)methane-1-ol, 3-(hydroxymethyl)-1-propynyl-imidazolidin-2,4-dione,    2-(hydroxymethyl)-4,5,6,7-tetrahydroisoindole-1,3-dione, {1-(2-propynyl)pyrrole-3-yl}methane-1-ol, 5-(hydroxymethyl)-4-methyl-(2-propynyl)-1,3-thazolin-2-one,    {1-(2-propynyl)-5-(trifluoromethyl)-4-pyrazolyl}methane-1-ol, 1-{1-(2-propynyl)-5-(trifluoromethyl)pyrrole-3-yl}prop-2-yne-1-ol, 1-{2-(trifluoromethyl)-1,3-thiazol-4-yl}prop-2-yne-1-ol, or 1-{2-(trifluoromethoxy)-1,3-thiazol-4-yl}prop-2-yne-1-ol.    
     
     
         10 . A process according to  claim 6 , wherein the monohydroxy compound of formula (1) is a benzyl alcohol substituted with a halogen atom.  
     
     
         11 . A process according to any of  claim 1 , wherein the zirconium compound of formula (6) is any one selected from the group consisting of tetramethoxyzirconium, tetraethoxyzirconium, tetrapropoxyzirconium and tetrabutoxyzirconium.  
     
     
         12 . A process according to  claim 11 , wherein the reaction of the monohydroxy compound of formula (1) with the carboxylic acid of formula (2) is conducted after removing a hydroxy compound of formula (7):  
         R 8 OH   (7)  
       wherein R 8  has the same meanings as above, which is by-produced by reacting the zirconium compound of formula (6) with the monohydroxy compound of formula (1).  
     
     
         13 . A process according to  claim 12 , wherein the hydroxy compound of formula (7) is removed in the presence of a solvent.  
     
     
         14 . A process according to  claim 13 , wherein the solvent is a solvent having higher boiling point than that of the hydroxy compound of formula (7), a solvent which can make an azeotrope with the hydroxy compound of formula (7), or a mixture of the solvent.  
     
     
         15 . A process for preparing a zirconium catalyst, which comprises reacting a zirconium compound of formula (6):  
         Zr(OR 8 ) 4    (6)  
       wherein R 8  is an alkyl group or an aryl group which may be substituted and is not the same as R 1 , with the monohydroxy compound of formula (1):  
         R 1 OH   (1)  
       wherein 
 R 2  is 
 an alkyl group which may be substituted,  
 an alkenyl group which may be substituted,  
 an alkynyl group which may be substituted,  
 an aryl group which may be substituted,  
 a heteroaryl which may be substituted,  
 an aralkyl group which may be substituted, or  
 a heteroarylalkyl group which may be substituted.  
 
 
     
     
         16 . A zirconium catalyst composition prepared by reacting a zirconium compound of formula (6):  
         Zr(OR 8 ) 4    (6)  
       wherein R 8  is an alkyl group or an aryl group which may be substituted and is not the same as R 1 ,  
       with the monohydroxy compound of formula (1) as defined in  claim 15 .  
     
     
         17 . A zirconium compound of formula (8):  
         Zr(OR 1 ) n (OR 8 ) 4-n    (8)  
       wherein R 1  is an aralkyl group which may be substituted, and R 8  is an alkyl group which may be substituted or an aryl group which may be substituted, and n is an integer of 1 to 4.  
     
     
         18 . A zirconium compound according to  claim 17 , wherein 
 R 1  is a benzyl group which may be substituted with at least one member selected from the group consisting of    a halogen atom, a propargyl group, and    methyl, methoxy, phenyl, phenoxy and methoxymethyl groups which may be substituted,    a cyano group and a nitro group.    
     
     
         19 . A zirconium compound according to  claim 18 , wherein R 1  is a benzyl group which may be substituted with at least one member selected from the group consisting of a halogen atom, and methyl, methoxy and methoxymethyl groups which may be substituted with halogen.  
     
     
         20 . A zirconium compound according to  claim 19 , wherein R 1  is a benzyl group substituted with a halogen atom.  
     
     
         21 . A zirconium compound according to any one of claims  18  or  20 , wherein n=4.  
     
     
         22 . A zirconium compound according to any one of  claims 18  to  20 , wherein R 8  is C 1-4  alkyl group.