Patent Publication Number: US-2012031771-A1

Title: Process for preparing reactive zinc by electrochemical reduction

Description:
The invention relates to a process for preparing reactive zinc by electrochemical reduction, wherein iron or steel is used as cathode material. 
     There is a great need for processes for preparing reactive zinc as starting material for functionalized metal-organic building blocks. These building blocks serve, for example, for the construction of pharmacologically relevant active compounds or complex agrochemicals. Thus, zinc organyls which can be obtained from reactive zinc can be used in transition metal-aided couplings to form C,C bonds, with allyl, aryl, alkenyl and alkynyl halides being able to be used as coupling participants. Furthermore, zinc organyls can be added onto carbonyl compounds, with chiral auxiliary reagents even making stereoselective transformations of this type possible. 
     The direct synthesis of zinc organyls from elemental zinc is possible in only few cases because of a passivating ZnO layer. These include the Reformatsky regents which are synthesized from commercial zinc powder and α-haloacetic esters. In addition, reactive halogen compounds, first and foremost alkyl iodides, can be reacted with unactivated zinc powder. A disadvantage of this reaction is that only zinc organyls of α-haloacetic esters or alkyl iodides and no other functionalized zinc organyls can be obtained, so that this method of preparation is very restricted and extremely substrate-specific. 
     However, the majority of zinc organyls cannot be obtained from unactivated, elemental zinc. Various processes for the activation of zinc and the subsequent syntheses of the corresponding zinc organyls have been described in the prior art. 
     In Handbook of Functionalized Organometallics—Applications in Synthesis, Wiley-VCH Verlag Weinheim, 2005, P. Knochel describes various methods of obtaining zinc organyls. These include transmetalation, chemical activation of zinc and the preparation of reactive zinc by chemical reduction. 
     For the purposes of the present invention, transmetalation is the reaction of a metal organyl with a usually inorganic metal salt, resulting in the organyl part being transferred from one metal to the other. Li and Mg organyls can also be used to generate the various corresponding zinc organyls. A great disadvantage of this process is that it is usually only possible to prepare unfunctionalized metal organyls since many functional groups are not compatible with Li and Mg organyls. Functional groups such as nitriles, carboxylic esters, ketones or tertiary amides are attacked by addition of Li and Mg organyls and are thus no longer available for further reactions. Other functions such as acetylides, secondary amides or nitro compounds which comprise moderately acidic protons can be deprotonated by strong metal organyls, as a result of which these, too, are no longer available for further reactions. 
     Zinc is chemically activated in classical processes by means of LiCI, iodide, dibromoethane or TMSCI as auxiliaries. All these reagents serve to overcome the passivating ZnO layer. The disadvantage of these reactions is that the chemical auxiliaries have to be added in substoichiometric or stoichiometric amounts and must not interfere in subsequent reactions of the zinc organyls. The use of these zinc organyls is therefore limited. 
     Rieke® zinc is a reactive zinc-comprising reagent which is obtained by chemical reduction of ZnCl 2  by means of lithium metal in the presence of naphthalene. This material has a very high reactivity compared to chemically activated zinc. This reactivity results from generation of the zinc under oxygen- and water-free conditions, as a result of which the formation of a passivating oxide layer is avoided. A disadvantage of this reaction is that lithium has to be used in stoichiometric amounts, so that high raw material costs are incurred and it is also necessary to accept an increased outlay for safety measures for handling the reactive alkali metal. 
     In Handbook of Functionalized Organometallics—Applications in Synthesis, Wiley-VCH Verlag Weinheim, 2005, P. Knochel also describes the electrochemical activation of zinc. WO-A 01/02625 describes the transition metal-catalyzed electrochemical reduction. Here, a zinc anode is dissolved anodically to generate Zn 2+ in solution. At the same time, the transition metal is reduced at the cathode, and is then inserted into the C-halogen bond and transfers the organic radical to the Zn 2+ . Transition metals which can be used are Ni, Co and Fe. A disadvantage of this method is the presence of the transition metal in the future product. The zinc organyl produced is inherently contaminated with the transition metal which can then also be present in the products of downstream stages. However, especially in the synthesis of pharmacological active compounds, contamination by transition metals has to be avoided and zinc organyls from the above-described method are therefore not suitable for this purpose. 
     In Tetrahedron 2005, 61, 11125-11131, N. Kurono, T. Inoue and M. Tokuda describe a further method for preparing reactive zinc by electrochemical reduction, namely electrogenerated zinc (EGZn). In this process, Zn is anodically dissolved in order to generate Zn 2+ ions in the solution. Zn 2+ is subsequently reduced by means of a redox mediator such as naphthalene or directly at the cathode and forms elemental zinc in solution. This is extremely reactive for insertions into C-halogen bonds since it does not comprise any passivating oxide layer. Disadvantages of this process are the use of Pt electrodes which cannot be used on an industrial scale and are too expensive and low temperatures in the range from 0 to −10° C. which would lead to increased costs. 
     It is therefore an object of the present invention to provide a process which makes it possible to prepare reactive zinc very inexpensively without the use of chemical reducing agents or reagents and can also be used on an industrial scale. 
     This object is achieved by a process for preparing reactive zinc, which comprises the following steps
         a) provision of an electrolysis cell having a cathode and a zinc anode,   b) charging of the electrolysis cell with an electrolyte selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-pyrrolidone and other tertiary amides which comprises an electrolyte salt selected from the group consisting of quaternary ammonium salts, organic metal salts and inorganic metal salts,   c) application of electric current to the cell until a 2-20% strength suspension of reactive zinc in the electrolyte has been formed,
 
wherein an iron or steel cathode is used as cathode and the electrochemical reduction is carried out at temperatures in the range from 20 to 60° C.
       

     The process of the invention is advantageous when N,N-dimethylformamide is used as electrolyte. 
     The process of the invention is advantageous when tetrabutylammonium tetrafluoroborate is used as electrolyte salt. 
     The process of the invention is advantageous when the electrolyte further comprises a redox mediator selected from the group consisting of naphthalene, N,N-dimethyl-1-naphthalene and further 1-substituted naphthalenes and also phenanthrene, anthracene, 4,4′-bipyridyl, and 4,4′-di-tert-butylbiphenyl. 
     The process of the invention is advantageous when the temperature at which the electrochemical reduction is carried out is in the range from 35 to 45° C. 
     The process of the invention is advantageous when a current density of from 1 to 4 A/dm 2  is set. 
     The process of the invention is advantageous when an undivided electrolysis cell is used. 
     The process of the invention is advantageous when an iron or steel tube is used as cathode and the zinc anode is arranged concentrically within the cathode. 
     The process of the invention is advantageous when it is carried out batchwise. 
     The process of the invention is advantageous when it is carried out continuously. 
     In the process of the invention, the activated zinc is produced by electrochemical reduction of zinc ions provided by dissolution of the zinc anode in an electrolysis cell. Any electrolysis cell known to those skilled in the art, e.g. a divided or undivided flow cell, capillary gap cell or plate gap cell, is suitable for this purpose. Preference is given to the undivided flow cell. 
     In the process of the invention, the electrolysis cell is equipped with a zinc anode and an iron or steel cathode. Any shape of an iron or steel cathode known to those skilled in the art, e.g. rod-like, as metal sheet, as iron or steel sheet shaped to form a tube, conically shaped iron or steel sheets, is suitable as cathode. 
     The zinc anode itself can likewise have any shape known to those skilled in the art, e.g. rod-like, as metal sheet, as cone or as loose electrode. The zinc anode is particularly preferably in the form of a rod, cylinder or cone. 
     Any arrangement of the anode relative to the cathode which is known to those skilled in art is possible for carrying out the process of the invention, e.g. arrangement opposite one another, parallel arrangement or a concentric arrangement in which the anode is positioned concentrically within the cathode. Preference is given to the zinc anode being arranged concentrically within the cathode. 
     The electrolysis cell is filled with an electrolyte. The electrolyte is selected from the group consisting of N,N-dimethylformamide, N,N-dimethylacetamide, N-methyl-pyrrolidone and other tertiary amides. Preference is given to N,N-dimethylformamide and N,N-dimethylacetamide. The use of N,N-dimethylformamide is particularly preferred. 
     In the process of the invention, the electrolyte further comprises an electrolyte salt selected from the group consisting of quaternary ammonium salts, organic metal salts and inorganic metal salts. Preference is given to tetrabutylammonium tetrafluoroborate, sodium methylsulfonate and zinc chloride. Very particular preference is given to tetrabutylammonium tetrafluoroborate. 
     As further additive, it is advantageous for the electrolyte to comprise a redox mediator. This is preferably selected from the group consisting of naphthalene, N,N-dimethyl-1-naphthalene and further 1-substituted naphthalenes and also phenanthrene, anthracene, 4,4′-bipyridyl and 4,4′-di-tert-butylbiphenyl. Particular preference is given to naphthalene. 
     In the process of the invention, the electrolyte is heated to temperatures in the range from 20 to 60° C., preferably in the range from 30 to 50° C., very particularly preferably in the range from 35 to 45° C. The temperature is regulated via a heat exchanger integrated into the electrolyte circuit. 
     In the process of the invention, a current density in the range from 1 to 4 A/dm 2  is applied at the anode and cathode. The current density is preferably in the range from 1.5 to 3 A/dm 2 , particularly preferably in the range from 1.5 to 2.5 A/dm 2 . 
     The electrolysis is stopped when the solids content of reactive zinc in the electrolyte has attained a theoretical content of 2-20% by weight, particularly preferably in the range from 2 to 10% by weight. 
     The process of the invention can be operated batchwise or continuously. In continuous operation, the electrolyte is discharged from the cell at a content of reactive zinc in the range from 2 to 20% by weight, preferably in the range from 2 to 10% by weight. At the same time, an equal amount of fresh electrolyte is introduced. This is continued until the zinc anode has to be replaced because of virtually complete dissolution. 
     When a tubular cathode surrounding the anode is used in the process of the invention, it is advantageous for the electrolyte to be circuited by pumping during the electrolysis. Preference is given to a pump circulation rate of from 100 to 600 l/h, particularly preferably from 300 to 600 l/h. 
    
    
     EXAMPLES 
     a) Reactive zinc in a glass beaker cell: current yield (9120-155) 
     0.65 g of Bu 4 NBF 4  and 1.25 g of naphthalene together with 61.00 g of DMF are placed in a glass beaker cell having a zinc anode and an iron cathode (electrode dimensions in each case 70×20×3 mm, immersed area 45×20 mm, spacing: 9 mm). After heating the electrolyte to 40° C., the electrolysis is started at a current of 0.2 A (corresponding to a current density of 2 A/dm 2 ). During the course of the electrolysis, the electrolyte darkens strongly and the voltage drops from 9.0 V to 5.5 V. After a running time of 12 hours, the electrolysis is stopped. A dark suspension of finely divided zinc is obtained. 
     Elemental analysis of the electrolyte gives a zinc (0) content of 2.7%, corresponding to a current yield of about 60%. 
     b) Reactive zinc in a glass beaker cell: reactivity (9120-172) 
     0.64 g of Bu 4 NBF 4  and 1.30 g of naphthalene together with 61.00 g of DMF are placed in a glass beaker cell having a zinc anode and an iron cathode (electrode dimensions in each case 70×20×3 mm, immersed area 45×20 mm, spacing: 9 mm). After heating the electrolyte to 40° C., the electrolysis is started at a current of 0.2 A (corresponding to a current density of 2 A/dm 2 ). During the course of the electrolysis, the electrolyte darkens strongly and the voltage increases from 8.0 V to 8.7 V. After a running time of 3.4 hours, the electrolysis is stopped. A dark suspension of finely divided zinc is obtained. 
     To test the reactivity of the electrochemically generated zinc, 1.00 g of 2-bromopyridine is added to the electrolysis output and the reaction mixture is heated at 80° C. for 0.5 h. After cooling, 2 ml of the reaction mixture is admixed with 4 ml of water and extracted with 4 ml of MTBE (methyl tert-butyl ether). Gas-chromatographic analysis of the organic phase indicates a conversion of 2-bromopyridine into pyridine of 86% (at a current yield of 60% as per example a) this corresponds to a reactivity of 70%). 
     c) Reactive zinc in a tube cell: current yield at full pump power (9120-169) 
     An electrolyte comprising 25 g of Bu 4 NBF 4  and 50 g of naphthalene in 2425 g of DMF is circulated by pumping at a pump rate of 600 l/h at 40° C. in an electrolysis cell having a steel tube as cathode (Ø=5.0 cm, l=55 cm, active electrode area 864 cm 2 ) and an internal zinc rod arranged concentrically thereto as anode (Ø=3.7 cm, l=55 cm, active electrode area 639 cm 2 ). 12.8 A are applied to the electrolysis cell for 8.4 h, with the voltage increasing from 6.0 V to 6.8 V. A dark suspension of finely divided zinc is obtained. 
     Elemental analysis of the electrolyte gives a zinc (0) concentration of 3.4%, corresponding to a current yield of 68%. 
     d) Reactive zinc in a tube cell: current yield at half pump power (9120-190) 
     An electrolyte comprising 25 g of Bu 4 NBF 4  and 50 g of naphthalene in 2425 g of DMF is circulated by pumping at a pump rate of 300 l/h at 40° C. in an electrolysis cell having a steel tube as cathode (Ø=5.0 cm, l=55 cm, active electrode area 864 cm 2 ) and an internal zinc rod arranged concentrically thereto as anode (Ø=3.7 cm, l=55 cm, active electrode area 639 cm 2 ). 12.8 A are applied to the electrolysis cell for 8.4 h, with the voltage initially increasing from 6.5 V to 9.9 V and dropping to 1.2 V over the further course of the electrolysis. A dark suspension of finely divided zinc is obtained. Elemental analysis of the electrolyte gives a zinc (0) concentration of 4.1%, corresponding to a current yield of 82%.