The Application of Ionic Liquids in Catholic Coupling of Acetophenone

Problem statement: The cathodic coupling of acetophnone was carried o ut in aqueous solutions containing sodium sulfate and 1-Octyl-3-M ethylimidazolium Chloride ([OMIM]Cl) as supporting electrolytes. [OMIM]Cl is an ionic liqui d, also serving as a co-solvent to prevent the depo sition of products during electrolysis. The products are e xtracted with ether after electrolyses. Approach: It is shown in this study that the recycling of the aqueo us Na2SO4-[OMIM]Cl electrolytes is feasible. Results: The new electrolytic process is more energy saving and environment-friendly than conventional ones. Conclusion: On the other hand, the ratios of dl-to meso pinacols formed in the electrochemical reduction of acetophenone can be more than 9, highe r than ever reported for any aqueous system.


INTRODUCTION
There has been a practical problem for most electroorganic reactions. Supporting electrolytes are necessary to pass the current through the electrolytic cell. However, the solubility of organic compounds in water is generally so low that organic solvents are preferred. Therefore, expensive quaternary ammoniums are used rather than cheap salts such as sodium sulfate, because these inorganic salts are insoluble in organic solvents. After electrolysis, the organic solvent is evaporated, the products are extracted and the quaternary ammonium is left in water phase. The conventional electrolysis process is not ideal at all when considering the following two questions: • How to recycle of the expensive quaternary ammoniums? • How to reduce the energy cost due to the high resistance of the cell when organic solvents are used?
Recently, there is a boom to apply ionic liquids on conventional reactions. Ionic liquids are inherently quaternary ammoniums. The role of quaternary ammoniums seems not simply to be supporting electrolyte, the function as catalyst is also possible. In addition, ionic liquids could be used as solvents to dissolve the reactants (Hapiod and Lagrost, 2008). Because of the immiscibility of ionic with most organic solvents and supercritical fluids, the products can be extracted after electrolysis, then the electrolytes containing ionic liquids can be ideally recycled for next electrolysis. This study is therefore aimed to pioneering a new way, which could be more energy-saving and environment-friendly than conventional electroorganic syntheses. Electroreduction of carbonyl compounds is a typical organic reaction using electrons as reagents. Generally, hydromonomer and hydrodimer are obtained simultaneously (Fig. 1).
There have been many studies concerning how to control the product-selectivity of hydrodimer to hydromonomer. Controlled potential electrolysis is generally effectual (Kodama et al., 2001;Janssen, 1988). Alternatively, a better mass-transfer condition can favor the production of hydrodimer under galvanostatic operation (Cheng and Nonaka, 1989;. Aqueous electrolytes without organic solvents are possible for electroreduction of acetophenone, if the substrate concentration is low enough and surfactants such as cetyltrimethylammonium bromide is used (Kodama et al., 2001). If ionic liquids are used rather than the common Energy Rec. J. 1 (2): [111][112][113][114][115]2010 quaternary ammoniums, solid at room temperature, what will be different in product-selectivity? This is one of the concerns in this research.
On the other hand, the stereo-selectivity of this reaction has been so interesting and investigated extensively. It is found the dl/meso rato of hydrodimer can vary from 0.3-19. Proton is a key factor, it is implied that aprotic environment favors the formation of dl-hydrodimer (Bewick and Brown, 1977;Bewick and Cleghorn, 1973;Smith and Utley, 1981;Stocker and Jenevein, 1968b;Maurice et al., 2000). It has been shown that the stereo-selectivity can also be influenced by ionic liquids. Lagrost et al. have found that the electroredutcion of acetophenone using an imidazolium-based ionic liquid ([BMIM][NTf 2 ]) resulted in a significantly lower dl/meso ratio (1.1) than those using trimethylbutylammonium and triethylbutylammonium salts did (3.3 and 3.7) (Lagrost et al., 2005). It is supposed that the interaction between imidazolium cations and acetophenone radical anions leads to the formation of ion-pairs, and coupling from two ion-pairs decreases the stereo-selectivity of the reaction. Initially, this study is aimed to selectively obtain meso-hydrodimer by using imidazolium-based ionic liquids. However, unexpected results are shown in the following experiments.

Reagents and materials:
In this study, 1-Octyl-3-Methylimidazolium Chloride ([OMIM]Cl) is selected as an imidazolium-type ionic liquid. It can be prepared from inexpensive materials and in high yield (Huddleston et al., 2001).
Acetophenone and 1-phenyl-1-ethanol (hydromonomer) are commercially available and were used without purification. The commercial available 2,3-diphenyl-2,3-butanediol (hydrodimer) is a mixture of dl-and meso-forms, n-hexane was used to recrystallized and separate the dl-form. The filtrate containing mainly meso-form was concentrated and transferred to an alumina column, then the meso-form was isolated by elution with benzene.
Deionized and distilled water was used for the preparation of aqueous solutions. All other reagents and solvents used are analytical grade. Electrode materials were purchased from Alfa Aesar.

Electrolysis:
The electrolytic cell is a H-cell divided by an Ionic MC-3470 cationic membrane (Sybron Chemicals Inc., USA). The cell is equipped with a copper or lead cathode and a graphite anode, both cylinder and with the same exposed area of 10 cm 2 .

Fig. 2: Electrolyte recycling scheme
Before electrolysis, Cu cathode was polished with 0.3 µm Al 2 O 3 and rinsed twice for 10 min with distilled water in an ultrasonic bath. Pre-electrolysis without carbonyl compounds was carried out for ca. 15 min in 0.5 M Na 2 SO 4 , unless otherwise stated. The rotation speed of the magnetic stirrer in cathodic chamber was set high enough to make emulsions in cases that immiscible co-solvents were used. The details of the electrolytic conditions are shown in Table 1 and 2.
According to the results in Table 1, the electrolytic conditions are modified for the test to recycle the electrolytes as shown in Fig. 2. The charge passed is 1.2 F for each cycle Analysis: After electrolysis, the catholyte was repeatedly extracted with the same volume of ether for 4 times. The combined extract was washed with a saturated NaCl solution and then dried over Na 2 SO 4 . After filtration, ether was evaporated and the residue was dissolved in isopropanol. The products were routinely analyzed using HPLC .

RESULTS AND DISCUSSION
Effect of co-solvents: The preliminary results are shown in Table 1. The best current efficiency for hydrodimer was 42% (Run 6) and 63% of acetophenone was converted to pinacol. The dl-form of pinacol is the major product. The yield of hydromonomer is generally no more than meso-pinacol, except in Run 4.      Fig. 3: The staggered conformation of 2,3-diphenyl-2,3-butanediol. In meso form, bond moments exactly cancel each other out, leading to be nonpolar The high ratios of dl-to meso-pinacol are extraordinary, because the reactions are processed in aqueous solutions. The reported dl/meso ratio seems not to exceed 4 for any protic environment, although more than 10 values are not rare for aprotic systems (Bewick and Brown, 1977;Bewick and Cleghorn, 1973;Smith and Utley, 1981). There were solid precipitates during electrolysis in Runs 1 and 2. These are not regarded as good electrolytic conditions. To avoid product precipitates, it is common to use more co-solvents such as ethanol or methanol. In more cases, aprotic solvents such as acetonitile or DMF are favored. As a co-solvent, [OMIM]Cl is better than ethanol, the voltage of the electrolytic cell is lower, and the products are more soluble in the aqueous mixture. If the organic solvent is not miscible with aqueous solution, the system will be an emulsion (Run 3). Emulsion electrolysis has its advantages, however, it is more complicated to control, because cathodic coupling possibly occurs in both aqueous and organic phases. It is evident that cosolvents other than [OMIM]Cl result in lower dl/meso ratios.
Water has a very high dielectric constant. By mixing [OMIM]Cl with aqueous Na 2 SO 4 , most electrolytes in the present research are considered to be much more polar than those protic environments in references. meso-Pinacol is nonpolar when it rotates to the staggered conformation, but dl-pinacol can not be (Fig. 3). Therefore, it is considered that more polar environment favors the production of dl-pinacol. The preference for the dl isomers has been generally attributed to inter-radical hydrogen bonding during dimerization (Stocker and Jenevein, 1968a;Pulisi et al., 1969). In this work, a new point of view is presented. The polarity of electrolytic environment is considered another important factor in controlling the stereoselectivity.
In Run 2, Ethanol (EtOH) was used as a co-solvent in addition to [OMIM]Cl, The existence of EtOH decreases the polarity of electrolytic environment and results in the lower ratios of dl/meso. The role of [OMIM]Cl in Run 3 is more complicated because of an emulsion system. The meso-hydrodimer is considered to form mainly in the much less polar environment of organic phase.

Effect of inorganic salts and electrode materials:
Not only aqueous sodium sulfate solution is miscible with [OMIM]Cl, other salts could be also used ( Table 2). The existence of ions with greater charge was expected to make the solution more polar, however, further promotion of dl/meso ratio did not succeed. It is well known that dl/meso ratio in acidic media is much less than that in neutral or basic media and the aqueous solution of aluminum sulfate is acidic. The results of Runs 8 and 9 imply that proton is more important than polar environment in controlling the stereo-selectivity. In addition, the electroreduction of acetophenone is almost suppressed by magnesium ions, as shown by very low current efficiency (Run 14). In this reaction, the cations could have many roles and further investigation is necessary to clarify the complexities.
From the viewpoint of energy cost, lead is better than copper as cathode material because of its higher hydrogen overvoltage and therefore higher current efficiency. However, relatively more hydromonomer forms on lead in basic media (Runs10-13).

Recycling test:
The catholyte was reused for 4 times. The results of recycling test are shown in Fig. 4. Current efficiency of hydrodimer increases from 45% in 1st cycle to 56% in 2nd cycle, while current efficiency of hydromonomer decreases from 19% in 1st cycle to 4.6% in 2nd cycle. On the other hand, dl/meso ratio increases form 7.9-8.9. After 2nd cycle, significant changes are not observed. This is consistent with the change of pH. The catholyte was initially neutral in 1st cycle. However, the consumption of proton during electrolysis was faster than the proton transfer from anolyte chamber through cation exchange membrane, therefore, the catholyte became more basic. After 2nd cycle, reproducibility was observed, it is because pH has approached a steady value.

CONCLUSION
Since the concentration of acetophenone could be rather high in the aqueous Na 2 SO 4 -[OMIM]Cl electrolytes, hydrodimer would be expected to be the major product under galvanostatic operation (Cheng and Nonaka, 1989; and the cell voltage could be much less than those using organic solvents as co-solvents. After extraction, the electrolyte could be recycled. Although many factors are not exactly controlled in the present study, reproducibility of this example implies that the recycling of the aqueous Na 2 SO 4 -[OMIM]Cl electrolytes is feasible.
Proton should be the major factor in controlling the stereo-selectivity of hydrodimers. However, the polarity of electrolytes seems potential to enhance the formation of dl-pinacol. The high polar electrolyte has been prepared by mixing ionic liquids with aqueous electrolytes. It is courageous that high dl/meso ratios could be therefore achieved even in aqueous solutions. Further investigations are now directed to improve the stereo-selectivity for dl-hydrodimer.