Method for the functionalization of conjugated or conjugatable derivatives assisted by a tempo-type electrophoric mediator

Abstract

The invention relates to a method for the functionalization of a chemical molecule having at least two double bonds or containing a double bond which is conjugated with a structure that is rich in electrons in the presence of a TEMPO-type electrophoric mediator and a nucleophilic agent. The functionalization method can also include a system for electrochemical regeneration of the electrophoric mediator.

1 . Method of functionalising a chemical molecule having at least two double bonds or containing one double bond conjugated with an electron-rich structure, in the presence of an electrophorus mediator and a nucleophile agent.  
   
   
       2 . Method according to  claim 1 , characterised in that it also includes a system of electrochemical regeneration of the electrophorus mediator.  
   
   
       3 . Method according to  claim 1 , characterised in that the electrophorus mediator is the oxidised form (oxoammonium or nitrosonium) of a molecule comprising at least one aminoxyl radical of Formula II:  
     
       
         
         
             
             
         
       
     
     in which R 1  and R 2  are groups, identical or different, cyclic or linear.  
   
   
       4 . Method according to  claim 1 , characterised in that the electrophorus mediator is the oxoammonium form of a chemical molecule from the bi-permethylated aminoxyl radical family, very preferably bi-permethylated aminoxyl radical containing at least one aminoxyl radical.  
   
   
       5 . Method according to  claim 1 , characterised in that this electrophorus mediator is 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) or 4-acetamido-TEMPO of Formulae III:  
     
       
         
         
             
             
         
       
     
   
   
       6 . Method according to  claim 1 , characterised in that the electrophorus mediator is used in stoichiometric quantity, according to a chemical method or an electrochemical method.  
   
   
       7 . Method according to  claim 6 , characterised in that the functionalisation is carried out at temperatures ranging from 0° C. to 80° C., preferably from 5° C. to 40° C.  
   
   
       8 . Method according to  claim 6 , characterised in that the functionalisation is carried out with a pH ranging from 0 to 13, preferably from 4 to 7.  
   
   
       9 . Method according to  claim 6 , characterised in that the functionalisation carried out using the chemical method comprises: 
 a first step, in which the molecule to be functionalised, at least one equivalent of mediator and at least one equivalent of the nucleophile compound are successively added to a reaction chamber containing an organic or hydro-organic reaction medium;    a second step in which the mixture is subjected to mechanical or magnetic stirring for 1 to 10 hours, preferably for 2 to 5 hours;    a third step in which the reaction mixture is purified.    
   
   
       10 . Method according to  claim 6 , characterised in that characterised in that the functionalisation carried out according to the electrochemical method comprises: 
 a first step in which an aminoxyl radical is inserted in at least stoichiometric quantity in an electrolytic solution containing a support electrolyte;    a second step in which, with zero potential, the molecule to be functionalised and at least one equivalent of nucleophile are successively inserted;    a third step in which the obtained raw product is purified.    
   
   
       11 . Method according to  claim 10 , characterised in that the oxidation reaction takes place by subjecting the working electrode to a potential that can be comprised between 0 and 1.2 volts, preferably between 0 and 0.6 volts in relation to an Ag/AgNO 3  reference electrode.  
   
   
       12 . Method according to  claim 10 , characterised in that the amount of mediator can be 0.5 to 5 equivalents in relation to the molecule to be functionalised, preferably from 1 to 4 equivalents.  
   
   
       13 . Method according to  claim 10 , characterised in that the solution can be stirred for a time comprised between 1 and 10 hours, preferably comprised between 2 and 5 hours.  
   
   
       14 . Method according to  claim 10 , characterised in that the electrophorus mediator is used in catalytic quantity and the electrophorus mediator is regenerated by an electrochemical system.  
   
   
       15 . Method according to  claim 14 , characterised in that the reaction takes place in an electrochemical reaction chamber, closed or circulating, made up of at least one working electrode (anode) and one auxiliary electrode (cathode), also comprising a reference electrode.  
   
   
       16 . Method according to  claim 15 , characterised in that the reference electrode is an Ag/AgNO 3  electrode, or a saturated calomel electrode (SCE), preferably an Ag/AgNO 3  electrode  
   
   
       17 . Method according to  claim 14 , characterised in that the working electrode is separated from the auxiliary electrode by an ion-exchange membrane such as Nafion®, preferably a cation-exchange membrane such as Nafion® 423.  
   
   
       18 . Method according to  claim 14 , characterised in that a catalytic quantity of aminoxyl radical, the molecule to be functionalised and an at least equivalent quantity of nucleophile are successively added to the electrolytic solution.  
   
   
       19 . Method according to  claim 14 , characterised in that the reaction takes place with a basic pH, comprised between 7 and 12, preferably between 9 and 11.  
   
   
       20 . Method according to  claim 14 , characterised in that the electrophorus mediator is in a quantity ranging from 2% to 50% in relation to the molecule to be functionalised, preferably between 5% and 30%.  
   
   
       21 . Method according to  claim 1 , characterised in that the reaction takes place in a reaction medium allowing the oxidation of the aminoxyl radical to oxoammonium ions (the mediator) and the functionalisation reaction and the solubilisation of the reactive species and of the support electrolyte if the reaction is carried out by the electrochemical method, chosen from among acetonitrile (ACN), tetrahydrofuran (THF), dimethylformamide (DMF), dimethylsulfoxide (DMSO) and any other mixture of water/organic solvent.  
   
   
       22 . Method according to  claim 21 , characterised in that when the molecule to be functionalised is not water soluble, acetonitrile (ACN) or dimethylformamide (DMF) are used dry or in the presence of a quantity of water ranging from 1% to 80% and preferably 5% to 40% when the chosen nucleophile is water.  
   
   
       23 . Method according to  claim 10 , characterised in that the reaction medium comprises a support salt that allows current to pass through the solution, at concentrations ranging from 0.02 M to 2 M, preferably from 0.05 M to 0.5 M.  
   
   
       24 . Method according to  claim 23 , characterised in that the salt is chosen from among NaClO 4 , LiClO 4 , LiCl.  
   
   
       25 . Method according to  claim 14 , characterised in that the reaction medium is a basic organic or hydro-organic medium with pH comprised between 7 and 12, preferably between 9 and 11  
   
   
       26 . Method according to  claim 25 , characterised in that the reaction medium comprises an organic or inorganic base that cannot be oxidised by the mediator, for example 2,6-lutidine or pyridine.  
   
   
       27 . Method according to  claim 25 , characterised in that the organic or hydro-organic medium contains NaClO 4  as the support salt.  
   
   
       28 . Method according to  claim 1 , characterised in that the nucleophile is a chemical molecule with excess electrons comprising at least one atom chosen from among oxygen (O), nitrogen (N), sulphur (S), fluorine (F) or iodine (I), preferably a chemical molecule comprising an atom chosen from among H 2 O, RCOO − , MeOH, N 3   − , SCN − , F − , I −  or CH 3 S − .  
   
   
       29 . Method according to  claim 1 , characterised in that the nucleophile is used in a quantity ranging from 1 to 10 equivalents and preferably from 1 to 5 equivalents.  
   
   
       30 . Method according to  claim 1 , characterised in that the chemical molecule to be functionalised is a linear or cyclic olefin  
   
   
       31 . Method according to  claim 30 , characterised in that the chemical molecule to be functionalised is a polyunsaturated fatty olefin.  
   
   
       32 . Method according to  claim 1 , characterised in that the functionalisation reaction and/or the oxidation reactions of the aminoxyl radical can be performed at a temperature ranging from 0° C. to 80° C., preferably from 2° C. to 40° C.  
   
   
       33 . Method according to  claim 1 , characterised in that it comprises an additional prior step of preparing the mediator.  
   
   
       34 . Method according to  claim 33 , characterised in that in the chemical method, the aminoxyl radicals are used in a quantity ranging from 1 to 4 equivalents in relation to the molecule to be functionalised  
   
   
       35 . Method according to  claim 33 , characterised in that in the electrochemical method, the aminoxyl radicals are used in a quantity that can range from 5% to 100% and preferably from 5% to 30% in relation to the molecule to be functionalised.