Synthesis of tyrosine derived diphenol monomers

Abstract

A method for preparing diphenol compounds, which method includes the steps of coupling a hydroxyphenyl carboxylic acid with a L-tyrosine ester in a water-miscible organic reaction solvent containing a carbodiimide capable of forming a water-solvent urea by-product, thereby forming a diphenol reaction product; and combining the reaction mixture with an amount of water effective to precipitate the diphenol as a water-immiscible organic phase, so that a water-immiscible organic phase is formed containing the diphenol reaction product. New diphenol monomers and polymers polymerized therefrom are also disclosed.

What is claimed is:  
     
       1. A method for preparing diphenol compounds having the formula:                    
       wherein R 1  is —CH═CH— or (—CH 2 —) n , in which n is zero or an integer from one to eight; and R 2  is selected from the group consisting of straight and branched alkyl and alkylaryl groups containing up to 18 carbon atoms; which method comprises the steps of: 
       coupling a hydroxyphenyl carboxylic acid having the formula:                    
       with a L-tyrosine ester having the formula:                    
       in a water-miscible organic reaction solvent containing a carbodiimide capable of forming a water-solvent urea by-product to form a diphenol reaction product; 
       combining the reaction mixture with an amount of water effective to precipitate the diphenol as a water-immiscible organic phase, so that a water-immiscible organic phase is formed containing the diphenol reaction product and a water-miscible phase is formed containing predominately reaction side-products and contaminants.  
     
     
       2. The method of claim  1 , wherein R 1  is (—CH 2 —) n , in which n is zero or an integer from one to three. 
     
     
       3. The method of claim  2 , wherein R 1  is —CH 2 -CH 2 —. 
     
     
       4. The method of claim  1 , wherein R 2  is selected from the group consisting of ethyl, butyl, hexyl, octyl and benzyl groups. 
     
     
       5. The method of claim  4 , wherein R 2  is a ethyl group. 
     
     
       6. The method of claim  1 , wherein said carbodiimide is selected from the group consisting of EDCI•HCL, 1-alkyl-3-(3-dimethylaminopropyl)carbodiimide (alkyl=isopropyl, cyclohexyl), 1-cyclohexyl-3-(2-morpholinyl-(4)-ethyl)carbodiimide, 1-cyclohexyl-3-(4-diethylaminocyclohexyl)carbodiimide, 1-cyclohexyl-3-(B-diethylaminoethyl)carbodiimide, 1,3-di-(4-diethylaminocyclohexyl)carbodiimide, 1-alkyl-3-(3-morpholinyl-(4)-propyl)carbodiimide (alkyl=methyl, ethyl), 1-benzyl-3-(3-dimethylamino-(N)-propyl)carbodiimide, 1-ethyl-3-(4-azonia-4,4-dimethylpentyl)carbodiimide; in each case—as the free base of salt selected from the group consisting of HCl, methiodide and metho-p-toluenesulfonate. 
     
     
       7. The method of claim  6 , wherein said carbodiimide is EDCI•HCL. 
     
     
       8. The method of claim  1 , wherein said reaction solvent is selected from the group consisting of THF, dioxane, dimethoxyethane, acetone, N-methyl pyrrolidinone and acetonitrile. 
     
     
       9. The method of claim  8 , wherein said solvent is THF. 
     
     
       10. The method of claim  1 , further comprising the step of separating said water-immiscible organic phase from said water-miscible reaction solvent. 
     
     
       11. The method of claim  10 , further comprising the step of precipitating said diphenol reaction product from said water-miscible organic phase. 
     
     
       12. The method of claim  10 , wherein said step of separating said water-immiscible organic phase comprises the step of extracting said water-immiscible organic phase into a solvent selected from the group consisting of methylene chloride, chloroform, or ethyl acetate. 
     
     
       13. The method of claim  12 , wherein said solvent is ethyl acetate for DTE or methylene chloride for all other monomers. 
     
     
       14. The method of claim  12 , further comprising the step of backwashing said extracted water-immiscible organic phase with an aqueous extraction medium. 
     
     
       15. The method of claim  14 , wherein said aqueous extraction medium is acidic. 
     
     
       16. The method of claim  14 , wherein said aqueous extraction medium is mildly basic. 
     
     
       17. The method of claim  12 , further comprising the step of precipitating said diphenol reaction product from said water-immiscible organic phase. 
     
     
       18. The method of claim  15 , further comprising the steps of: 
       backwashing said aqueous extraction medium with the water-immiscible organic phase extraction solvent;  
       combining said water-immiscible organic solvent phases; and precipitating said diphenol reaction product from said combined water-immiscible organic solvent phases.