Study On Electrochemical Carboxylation Of Unsaturated Compounds Containing Double Bond With Carbon Dioxide

In order to avoid the severe pollution caused by the traditional chemical industry to the human-reliable earth environment, the green chemistry gradually becomes more and more promising. Because green chemistry is in principle based on the abatement of the waste of solution, gas and solid including all the harmful trashes and production of environmental benign compounds together with a green process. Carbon dioxide is the most dominating greenhouse gas. However, it can be propsed as the most abundant and cheapest C1 building block in the organic synthesis from an opposite view. Therefore great effort has been placed toward fixation of CO2 to reduce the greenhouse effect and improve the catastrophic events. However, owing to the high thermodynamic stability of CO2, effective activation of it has become a problem. Electrochemistry can work this out by the electron transfer between the electrode and substrates without additional redox reagents. Essentially, organic electrosynthsis would probably eliminate the environmental pullation from the source to be a new "green" synthetic technology.a-Hydroxy acids (AHAs) has been widly used to synthesize one impartant class of nonsteroidal anti-inflammatory pharmaceutical. There have been many reports about electrosynthesis of AHAs, however, the carboxyaltion yields are not always very satisfying and need of using highly toxic mercury/lead or the costly platinum cathode material makes this process less attractive and somewhat troublesome from the view point of industry. Amino acids are used as an elementary substrate to compose the necessary protein to biological movement which could be synthesized via traditional organic reactions such as Hell-Volhard-Zelinsky reaction, Gabriel reaction or using propanedioic acid eater as the reactant. The synthetic procedures are comparatively complex and fussy and some of the reactions need performing in a close vessel or autoclave which definitely goes against the principles of green chemistry. There are only a few examples of electrocarboxylation of conjugated dienes in the presence of CO2, the difficulty and characteristic of which is the disorder of the distribution law of aimed products.Asymmetric electrochemical carboxylation has been challenging for many years due to the diffculty in selective fixation of the small molecule of carbon dioxide since it has been known that enantioselective electron transfer is not possible in principle and the electron cannot possess chirality. Usually, chiral solvents and supporting electrolytes need large amounts of optically active materials inherently. By contrast, only catalytic amounts of chiral materials are necessary when chiral electrodes including chiral electrode suface-active materials, chiral chemically modified electrodes and optically active polymer-coated electrodes are used as the chiral auxiliary. As far as we hnow, only a few asymmetric electrochemical carboxylation was reported up to now.The study on electrochemical activation and fixation of greenhouse gas of carbon dioxide to a-hydroxy acids, dicarboxylated acid ester, N-substituted amino acid derivative, etc. possess series of advantaged of mild conditions, simple operation, high selectivity compared to traditional ouganic synthesis. Specially, application of the chiral electrode in asymmetric electrocarboxylation of prochiral sustrate is particularly new all over the world with a very promising prospect.The details are given as follows:(1) Electrocarboxylation of unsaturated aromatic compounds including C=O bondComparative electrochemical behavior of series of aromatic aldehyde or ketone including benzaldehyde,p-methoxybenzaldehyde, acetophenone, p-methoxyacetophenone,p-methylacetophenone,4-cyanoacetophenone, propiophenone,p-methylpropiophenone, benzophenone were studed by cyclic volmmetry in the solution of 0.1 mol L-1 TEABF4-DMF in a conventional three-electrode cell with the glassy carbon disk as the working electrode, a platinum spiral as the counting electrode and Ag/AgI/O.1mol L-1 TBAI as the reference electrode. Potential law was then investigated by calculating respective electrochemical parameters of various substrated influenced by distinct substitution effects.In one compartment electrochemical cell equipped with magnesium as the sacrificial anode, stainless steel (Ss), titanium (Ti), copper (Cu), nickel (Ni), silver(Ag) as the cathode and in the DMF solution saturated with carbon dioxide, the aimed product 2-hydroxy-2-(4-methoxy-phenyl)-propionic acid methyl ester was electrosynthesized via electrochemical fixation of carbon dioxide. Under the various controlled current conditions, electrocarboxylation of p-methoxylacetophenone was measured as a function of supporting electrolytes, cathode materials, the current density, passed charge and temperatures. After systematic optimization, the maximal yield of 63% was achieved when the electrolysis was carried out at a controlled current density of 5.0 mA cm-2 until theoretical charge passed through the cell. Furthermore, the electrochemical behavior of p-methoxylacetophenone was studied in a three-electrode system, with a glassy carbon as the working electrode (d=3.0 mm), a platinum spiral (Pt) as the counter electrode and Ag/AgI/0.1 mol L-1 TBAI in DMF as the reference electrode. The possible electrocarboxylation mechanism was put forward accordingly, which suggested a typical ECE (one electron reduction chemical reaction-another electron reduction) process.In one compartment electrochemical cell 2-hydroxy-2-p-tolyl-butyric acid methyl ester was electrosynthesized by electrochemical carboxylation of p-methylpropiophenone in the presence of carbon dioxide. By potentiostatic electrolysis, the electrocarboxylation was first studied by varying the solvent and the kind of supporting electrolyte. Then other conditions including cathode materials, the current density, passed charge and temperatures were further studied under galvanostatic control. As a result, the excellent yield of 97% was obtained when the electrolysis was carried out in DMF-0.1 mol·L-1 tetraethylammonium bromide (TEABr) solution using cheap and environmentally benign nickel as the cathode under a controlled current density of 5.0 mA·cm-2 until 2.8 F·mol-1 charge passed through the cell at-10℃. The electrochemical behavior of p-methoxylacetophenone was studied on the glassy carbon electrode by cyclic voltammetry and the probable mechanism was proposed accordingly, which suggested a typical ECE (one electron reduction-chemical reaction-another electron reduction) process.(2) Asymmetric electrocarboxylation of unsaturated aromatic ketone including C=O bondThe chiral HPLC methods were established for the enantiomeric separation of four kinds of important anti-inflammatory medical intermediates: phenylhydroxyacetic acid (mandelic acid) 2-hydroxy-2-phenyl propanoic acid (atrolactic acid),2-hydroxy-2-(4-methoxyphenyl) propanoic acid,2-hydroxy-2-(4-methylphenyl) butyric acid. Based on the mobile phase consisting of n-hexane, ethanol and trifluoroacetic acid (TFA), the functionary law and separation rules between the separated enantiomers and the chiral stationary phase were specially discussed by varying the ratio of n-hexane/ethanol, the kind of alcohol and different proportions of trifluoroacetic acid additive. Furthermore, the corresponding enantiomers of the four kinds ofα-hydroxy acids were completely separated on the chiralpak AD-H column with optimal chromatographic profiles.A novel method of selective fixation of carbon dioxide was developed in this work. In an undivided cell the pharmaceutically active 2-hydroxy-2-phenylpropionic acid (atrolactic acid) has been produced from prochiral acetophenone in the presence of two kinds of chiral alkaloids, cinchonidine and cinchonine, acting as the inductors which were inclined to afford R and S products respectively. Since the alkaloid has a strong tendency to adsorb to the surface of the cathode, three different cathode materials (stainless steel, platinum, copper) were applied in the process of asymmetric electrochemical carboxylation. Using cinchonidine and cinchonine as the inductors, the electrocarboxylation yield as well as the ee value of the aimed 2-hydroxy-2-phenylpropionic acid was also measured as a function of the concentration ratio of the alkaloid to the cocatalyst of butanol, supporting electrolyte, temperature, charge passed, current density, solvent. In particular, the butanol may play a critical role of helping to accomplish the asymmetric electrocarboxylation induction. From further analysis of cyclic voltammograms of acetophenone before and after addition of the alkaloid and butanol, a possible induction mechanism was put forward accordingly. (3) Electrocarboxylation of aliphatic conjugated dienes including C=C bondUnder mild condtions, electrocarboxylation of methyl sorbate chosen as the. modal diene was first investigated by activation and fixation of greenhouse gas of atmospheric carbon dioxide. The yields of three isolated products were influenced by various experimental conditions including solvent, cathode material, current density, passed charge and temperature. After initiall optimization, the overall yield of 47% with the 26% carboxylated yield could be achieved when the electrolysis was carried out in the 0.1 mol L-1 TBAP-DMF at a controlled current density of 5.0 mA cm-2 until theoretical charge passed through the cell at-10℃using stainless steel as the working electrode and sacrificial magnesium as the anode.On the basis of optimized condition of electrocarboxylation of methyl sorbate electrochemical carboxylation of three other conjugated diene strutures including 3-methyl-1,3-pentadiene,2,4-dimethyl-1,3-pentadiene,2,5-dimethyl-2,4-hexadiene with different substitution effect was comparatively studied. As a result, electrocarboxylation of 3-methyl-1,3-pentadiene gave exclusive product, electrocarboxylation of 2,4-dimethyl-1,3-pentadiene gave two isomeric carboxylated compounds which were hard to isolate and electrocarboxylation of 2,5-dimethyl-2,4-hexadiene even could not be realised due to its strong electron-danating effect.The electrochemical behavior of four conjugated dienes was then studied on the glassy carbon electrode by cyclic voltammetry and the probable mechanisms were proposed accordingly. Furthermore, some gas-phase geometry optimizations and semiempirical calculations have been done using Gaussian03W program, which definitely offered some corroboration to the speculated mechanism.(4) Electrocarboxylation of [(4-methoxy-benzylidene)-amino]-acetic acid ester including C=N bondIn the undivided cell, electrocarboxylation of [(4-methoxy-benzylidene)-amino]-acetic acid ester, in which the nitrogen atom of the C=N was substituted by the aliphatic group was investigated for the first time in the DMF solution saturated with CO2 using magnesium rod as the sacrificial anode. Finally, C-carboxylated, N-carboxylated and C,N-carboxylated products were obtained whose yields were influenced by various reaction conditions including the supporting electrolyte, cathode material, current density, charge passed and temperature. After preliminary optimization, the total carboxylation yield of 37.3% could be achieved with a ratio between the three products of 14.1:5.7:13.8. Using glassy carbon as the working electrode, the electrochemical behavior of the [(4-methoxy-benzylidene)-amino]-acetic acid ester was studied by cyclic voltammetry. Based on the character in the absence of presence of carbon dioxide, the possible electrocarboxylation scheme was postulated accordingly.