RSC Advances This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. View Article Online PAPER View Journal | View Issue Electrocarboxylation of 1-chloro-(4- Cite this: RSC Adv., 2019, 9, 15115 isobutylphenyl)ethane with a silver cathode in ionic Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. liquids: an environmentally benign and efficient way to synthesize Ibuprofen† Silvia Mena, Jessica Sanchez and Gonzalo Guirado * Electrocarboxylation of organic halides is one of the most widely used approaches for valorising CO2. In this manuscript, we report a new greener synthetic route for synthesising 2-(4-isobutylphenyl)propanoic acid, Ibuprofen, one of the most popular non-steroidal anti-inflammatory drugs (NSAIDs). The joint use of electrochemical techniques and ionic liquids (ILs) allows CO2 to be used as a C1-organic building block for synthesising Ibuprofen in high yields, with conversion ratios close to 100%, and under mild conditions. Furthermore, the determination of the reduction peak potential values of 1-chloro-(4- isobutylphenyl)ethane in several electrolytes (DMF, and ionic liquids) and with different cathodes (carbon Received 8th March 2019 Accepted 9th May 2019 and silver) makes it possible to evaluate the most “energetically” favourable conditions for performing the electrocarboxylation reaction. Hence, the use of ILs not only makes the electrolytic media greener, but DOI: 10.1039/c9ra01781j they also act as catalysts enabling the electrochemical reduction of 1-chloro-(4-isobutylphenyl)ethane to rsc.li/rsc-advances be decreased by up to 1.0 V. use of organic electrochemical techniques for obtaining high 1. Introduction valuable carboxylation products, since they can improve envi- Carbon dioxide (CO2) is known as a greenhouse gas and is the ronmental conditions. In this sense, electrochemical tech- most important contributor to global warming. The chemical niques may offer the possibility to activate the CO2 through properties of CO2 make it an interesting candidate for devel- a electrocarboxylation process.10–19 Electrocarboxylation of oping new green sustainable chemistry, since it is abundant, organic halides is one of the most widely used approaches for non-toxic, non-ammable, and a low cost material. Moreover, valorising CO2. In a rst step, a one electron transfer process its C1 carbon skeleton is interesting for making longer mole- generates the organic radical, which later converts to an anion cules. Therefore, one of the main challenges for the scientic though a second reduction electron transfer, and a halide anion community is to eliminate or re-use CO2 in order to obtain other (Scheme 1).20 The key step of this approach relies on the types of compounds with high added value, such as carboxylic reduction potential value of the organic halides and on the derivatives. In this sense, different methodologies are currently stability of the organic anion formed aer the reduction being developed to minimise its production, such as the carbon process. Furthermore, in the recent years, many studies have capture and storage (CCS) and carbon capture and utilisation appeared in which a silver electrode is a good option to reduce (CCU) technologies.1–6 the reduction potential in the carbon–halide cleavage According to the literature,7–9 different organic synthetic reaction.21–29 routes have been developed using CO2 as a reactant. Direct The electrochemical approach for synthesis of non-steroidal carboxylation of carbon nucleophile using CO2 as an electro- anti-inammatory drugs (NSAIDs) (e.g. Naproxen30 and phile is a straightforward route to prepare carboxylic acids. On Ibuprofen30–32) has been previously performed, obtaining from the other hand, CO2 is highly reactive with carbon nucleophiles, moderate to good yields. However, the main drawbacks asso- such as Grignard and organolithium reagents. The main ciated with those electrocarboxylation processes were the use of disadvantage of those processes is the use of toxic reagents that organic solvents, which are well-known to be hazardous and generate a large amount of waste. An attractive alternative is the ammable,14 the use of large quantities of supporting electro- lyte,16 and either the use of toxic redox mediators, or high reduction potential values. In this sense, in the current manu- Departament de Quı́mica, Universitat Autònoma de Barcelona, 08193-Bellaterra, script we propose an attractive alternative to these electro- Barcelona, Spain. E-mail: gonzalo.guirado@uab.cat carboxylation processes by: (1) the replacement of conventional † Electronic supplementary information (ESI) available. See DOI: electrochemical solvents with Ionic Liquids (ILs). ILs have been 10.1039/c9ra01781j This journal is © The Royal Society of Chemistry 2019 RSC Adv., 2019, 9, 15115–15123 | 15115 View Article Online RSC Advances Paper This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Scheme 1 Electrochemical carboxylation mechanism of benzyl halides. widely used as environmentally friendly solvents, electrolytes, aqueous saturated calomel electrode (SCE) isolated from the as well as catalysts,33–41 and (2) the use of a silver cathode for working electrode compartment by a salt bridge. The salt decreasing the reduction potential values required for the solution of the reference calomel electrode is separated from Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. cleavage of the halide–carbon bond, avoiding the use of either the electrochemical solution by a salt-bridge ended with a frit, toxic mediators. Hence, this manuscript reports a new, more which is made of a ceramic material, allowing ionic conduction environmentally friendly, approach for synthesising 2-(4-(2- between the two solutions and avoiding appreciable contami- methylpropyl)phenyl)propanoic acid (Ibuprofen) by using green nation. Ideally, the electrolyte solution present in the bridge is technologies (electrochemistry), green solvents (RTILs), and the same as the one used for the electrochemical solution, in CO2 feedstock. order to minimise junction potentials. The error associated with the potential values is less than 5 mV. The ohmic drop can be one of the main sources of error when ILs are used as solvents, 2. Experimental section since they are more resistive media than aprotic polar solvents 2.1. Materials with 0.1 M concentration of supporting electrolyte. Carbon dioxide, CO2, and nitrogen, N2, were obtained from The number of electrons involved in the rst reduction Carburos Metálicos S.A. (a purity of 99.9999%). 1-Chloro-(4- process of 1 was determined by comparison with very well- isobutylphenyl)ethane (1) was synthesised following that in the known one-electron reduction of uorenone and nitrobenzene literature.42 N-Methyl-N-propylpiperidinium bis(tri- (redox probes), in the same medium using the same electro- uoromethanesulfonyl)imide (PP13 TFSI, purity 99.5%, H2O # chemical set-up, by terms of cyclic voltammetry. The number of 0.05%), 1-methyl-1-ethylimidazolium bis(tri- electrons involved in this rst electron transfer was also uoromethanesulfonyl)imide (EMIM TFSI, purity 99%, H2O # conrmed by controlled-potential electrolysis.43–46 0.2%) were acquired from Solvionic, and were dried under vacuum using activated molecular sieves for 24 h to make sure 2.3. General procedure for the electrocarboxylation that the amount of water was always less than H2O # 0.001% processes (Scheme 2). Compound 1 was electrolysed at a negative potential of 0.1 V more negative than the Epc potential value under nitrogen or 2.2. Cyclic voltammetry experiments carbon dioxide saturated solutions. When the reaction is An electrochemical conical cell is used for the set-up of the completed, the resulting solution in the electrolysis is extracted three-electrode system. For CV experiments, the working elec- into water/ether mixtures. The organic layer is dried with trode is a vitreous carbon disk of 1 mm diameter. It is polished Na2SO4 and evaporated to yield a residue that is analysed by gas using a 1 mm diamond paste. The counter electrode is a Pt disk chromatography-mass spectrometry, and Proton Nuclear of <1 mm diameter. All the potentials are reported versus an Magnetic Resonance (1H-RMN). When pure ILs are used as Scheme 2 Diagram of the structures. 15116 | RSC Adv., 2019, 9, 15115–15123 This journal is © The Royal Society of Chemistry 2019 View Article Online Paper RSC Advances electrolyte, the products of the electrolysed solution are extracted with ether, allowing to recover almost an 80% of the IL at the end of the experiment. This organic layer was lately washed with water and dried with Na2SO4 (Scheme 3). Besides, This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. the IL recovered was dried and reused in a new electrochemical process without loss of Ibuprofen yield. All products obtained, and the commercial analogues (1- chloro-(4-isobutylphenyl)ethane, 1-ethyl-4-isobutylbenzene, 2- (4-(2-methylpropyl)phenyl)propanoic acid) were characterised by 1H-NMR. Measurements were made using a Bruker DPX360 (360 MHz) (Billerica, MA, USA) spectrometer. Proton chemical Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. shis were reported in ppm (d) (CDCl3, d ¼ 7.26, or CD3CN, d ¼ 1.94). The J values are reported in Hz. 2.4. Determination of the CO2 concentration in ILs A thermal mass owmeter of modular construction with Fig. 1 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C on GC a ‘laboratory style’ pc-board housing (EL-FLOW® Mass Flow electrode of a solution of 10 mM of 1 in DMF + 0.1 M TBABF4 (black line), PP13TFSI (blue line), DMF–PP13 TFSI (50 : 50) and EMIM TFSI (red Meter/Controller) from Bronkhorst Hi-Tec, was used to monitor line). the CO2 concentrations in the solution.47 Control valves were integrated to measure and control a gas ow from the lowest range of 0.2 up to 10 ml min1. detected, which is attributed to the oxidation of chloride anion.49 A closer look at the CVs also reveals that when EMIM TFSI is used as a solvent, a new peak appears 0.3 V vs. SCE. 3. Results and discussion This new peak is oxidation related to imidazolium moieties 3.1. Electrochemical reduction of 1-chloro-(4- formed aer the electrochemical reduction of EMIM. This IM isobutylphenyl)ethane (1) under inert atmosphere radical is immediately reduced at the electrode surface to its Cyclic voltammetry of compound 1 was recorded in different anion, and on the CV return its oxidation is observed at ca. 0.1 V solvents (DMF + 0.1 M TBABF4, EMIM TFSI, PP13 TFSI, and vs. SCE.50–54 The cyclic voltammograms performed in PP13 TFSI a DMF–PP13 TFSI (50 : 50)), and scan rates using glassy carbon and DMF–PP13 TFSI also show an irreversible oxidation peak at electrode as a cathode under a N2 atmosphere. In all cases, 0.28 V in the corresponding anodic counter scan. The compound 1 shows a two-electron irreversible reduction peak appearance of this peak indicates that a new electroactive (Fig. 1), as was expected for these types of compounds. The species is present in the solution. Hence, the oxidation peak number of electrons involve in the rst reduction process is should be associated with the oxidation of the benzylic anion determined by comparison with the uorenone, our standard, intermediate 1 (Schemes 4 and 5, Fig. 2). The irreversible wave in the same medium and with the same electrochemical set-up. at Epa ¼ 0.28 V vs. SCE disappears upon the addition of water Hence, in a rst cathodic scan, a two electron irreversible and acid, which agrees with the presence of the anionic reduction wave appears between 1.9 and 2.4 V vs. SCE, intermediate. depending on the solvent. The peak width value (DEp) is always Taking the value Epc value obtained for the electrochemical more than 150 mV (at 0.3 V s1, Table 1), which means that reduction of 1 in DMF + 0.1 M TBABF4 as a reference value compound 1 shows a slow electron transfer (charge transfer (Table 1), the Epc values obtained in all the ILs are positively coefficient (a) ca. 0.3).48 The analysis of the peak current values shied, which means that the cation of the IL acts as a catalyst (and their dependence with the concentration and the scan (as was previously pointed out by us and some other authors).35 rate), the peak potential values (and their dependence with the The reduction potential can be lowered to more than 0.30 V concentration) indicates that the chemical reaction coupled to (7 kcal mol1) with respect to DMF + 0.1 M TBABF4 (Table 1, the electron transfer is a rst order reaction. In the corre- entries 1–4). This fact can be explained by taking in to account sponding anodic counter scan an oxidation peak at ca. 1.1 V is that the IL is a pure ion solvent, whereas the concentration of Scheme 3 Schematic process for Ibuprofen purification and IL recovery after the electrocarboxylation reaction. This journal is © The Royal Society of Chemistry 2019 RSC Adv., 2019, 9, 15115–15123 | 15117 View Article Online RSC Advances Paper Table 1 Cathodic peak potential (Epc in V), DEp ¼ |Epc  Epc/2| (in mV), scan rate: 0.3 V s1, concentration ca. 5 mM, Charge transfer coefficient (a) for 1 in several solvents using glassy carbon as a working electrode at 25  C under nitrogen atmosphere Entry Solvent Epc (V) DEpb (mV) a Number of electrons This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. 1 DMFa 2.42 180 0.261 1.95 2 EMIM TFSI 2.03 156 0.313 2.12 3 DMFa–PP13 TFSI (50–50%) 2.18 180 0.265 2.03 4 PP13 TFSI 2.15 212 0.222 1.85 a The DMF solution contains 0.1 M of N-tetrabutylammonium tetrauoroborate (TBABF4). b DEp (mV) is the peak width value Epc  Epc/2 at 0.3 V s1. Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. the counter-cation is considerably lower the DMF solution, (electrochemical reaction, E), which undergoes C–Cl cleavage, where “only” a 0.1 M concentration of tetrabutylammonium leading to the corresponding organic radical and halide anion cation is present. (elementary reaction step, C). The radical is reduced at this In order to determine the nature of the product formed potential value, leading to the corresponding anion (electro- aer the rst electron transfer of 1, a control potential elec- chemical reaction, E). In a last protonation step the organic trolysis at 2.2 V vs. SCE under inert atmosphere was per- anion evolves to 2. formed in the above-mentioned electrolytic media (a control When EMIM TFSI is used as solvent the reactant was recov- potential electrolysis at 2.5 V vs. SCE was performed in DMF). ered at the end of the process, and only decomposition products 1-Ethyl-4-isobutylbenzene, 2, was obtained as a unique quan- related to the reduction of EMIM cation were observed. These titative product (100%) in DMF, DMF/PP13, and PP13 aer the results can be easily rationalised taking into account that EMIM passage of 2F. Overall, the electrochemical reduction mecha- cation is reduced at 2.3 V, so the solvent is partially reduced at nism of 1 is a two electron ECE mechanism (Scheme 4). In this potential. Thus, EMIM TFSI was discarded for the a rst reduction step, a radical anion is formed upcoming electrocarboxylation processes. Scheme 4 Electrochemical reduction mechanism of 1. 15118 | RSC Adv., 2019, 9, 15115–15123 This journal is © The Royal Society of Chemistry 2019 View Article Online Paper RSC Advances This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Scheme 5 Electrocarboxylation of 1 under CO2 atmosphere adding MeI as methylated agent at the end of the controlled-potential electrolysis. 3.2. Electrochemical reduction of 1-chloro-(4- a methylated agent, such as iodomethane, was added it is isobutylphenyl)ethane (1) under CO2 atmosphere with carbon possible to obtain methylated Ibuprofen, 4 (Scheme 5). Finally, Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. vitreous working electrode note, that for obtaining yields close to 100%, the IL should be previously dried, the use of commercial IL (#0.05% water Fig. 2 shows the cyclic voltammograms of 1 in one of the elec- content) also leads also to 20% of protonated compound 2. trolytic media employed under CO2 atmosphere. In all the cases, a two electron reduction wave was observed at ca. 2.20 V vs. SCE in the initial cathodic scan, whereas an oxidation peak 3.3. Electrochemical reduction of 1-chloro-(4- at ca. 1.1 V vs. SCE, which corresponds to the oxidation of isobutylphenyl)ethane (1) under CO2 atmosphere with silver chloride ion, is also detected in the ensuing anodic scan. working electrode Taking advantage of the long lifetime of 1 in ionic liquid It is well-known that the use of silver cathodes reduces the based electrolytes, several electrocarboxylation processes where reduction potential value where the carbon–halide cleavage attempted. The selected electrolyte was previously pre-saturated reaction takes place.21–29 Due to the electrocatalytic effect of with CO2 to minimise undesired protonation side reactions. silver, it was decided to use a silver electrode as a cathode for the Hence controlled-potential electrolysis of 1 was performed electrocarboxylation process in ILs. using a graphite bar electrode under a saturated CO2 atmo- Cyclic voltammetry of compound 1 was recorded, using sphere in DMF and ILs. The reduction processes were easily a silver electrode as a cathode under N2 atmosphere, in EMIM monitored by means of cyclic voltammetry (Fig. 3). In all the TFSI (to try to improve the results obtained with the carbon cases Ibuprofen was obtained in moderate to good yields (Table electrode) and PP13 TFSI (Fig. 4). In all cases, compound 1 2). The used of PP13 TFSI IL as a co-solvent, not only makes the shows the same general behaviour as in the case of using reaction greener, but also increases the yield up to 75%. This a glassy carbon electrode. Hence, in a rst cathodic scan, a two result can be explained due to a higher hydrophobicity of the electron irreversible reduction wave appears between 1.7 and media, since these electrocarboxylation reactions are very 2.0 V vs. SCE depending on the ionic liquid. Taking the Epc sensitive to the presence of water. Finally, when pure IL elec- value obtained for the electrochemical reduction of 1 in the trolyte is used, the product yield increases up to ca. 90% over ionic liquids with glassy carbon electrode as a reference value consumed reactant, with the E-factor being close to 1 (Table 2, (Table 1), the Epc values obtained using silver electrode are entries 5 and 10). Hence, no other products apart from the considerably positively shied. The reduction potential can be Ibuprofen and the starting material were recovered. Moreover, lowered to more than 0.07 V (1.61 kcal mol1) and 0.49 V Fig. 2 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C on a GC Fig. 3 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C on a GC electrode of 10 mM of 1 at CO2 atmosphere (blue line), inert atmo- electrode showing controls of the control potential electrolysis of 1 at sphere (black line) in PP13 TFSI–DMF (1 : 1). CO2 atmosphere in DMF–PP13 TFSI (1 : 1). This journal is © The Royal Society of Chemistry 2019 RSC Adv., 2019, 9, 15115–15123 | 15119 View Article Online RSC Advances Paper Table 2 Results of electrocarboxylation of 1 to obtain R–COOH/Me R–COOH (Ibuprofen isolated yield) Reagent recovery R–H Entry Solvent Eapplied C mol1 Yielda (%) Conversion rateb (%) (%) (%) This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. 1 DMFc 2.6 3.0 61 82 26 13 2 EMIM TFSI 2.2 3.0 — — — — 3 DMF-ILd (50–50%) 2.4 3.3 75 83 10 15 4 PP13 TFSIe 2.4 1.7 25 57 56 19 5 PP13 TFSIf 2.4 1.7 47 94 50 3 R–COOMe (methylated Ibuprofen Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. isolated yield) Reagent recovery R–H Solvent Eapplied C mol1 Yield (%) Conversion rate (%) (%) 6 DMFc 2.6 3.0 61 87 30 9 7 EMIM TFSI 2.2 3.0 — — — — 8 DMF-ILd (50–50%) 2.4 3.0 86 86 — 14 9 PP13 TFSIe 2.4 1.7 26 67 61 13 10 PP13 TFSIf 2.4 1.7 48 96 50 2 a Percent yield over isolated product. b Percent of Ibuprofen over consumed reactant. c The DMF solution contains 0.1 M of N-tetrabutylammonium tetrauoroborate (TBABF4) dried under vacuum and molecular sieves (less than 0.01% of water). d Mixture 1 : 1 of DMF + 0.1 M TBABF4 and PP13 TFSI dried under vacuum and molecular sieves (less than 0.01% of water). e PP13 TFSI commercially available 0.05% of water. f PP13 TFSI dried under vacuum and molecular sieves (less than 0.01% of water). Fig. 5 shows the cyclic voltammogram of 1 in PP13 TFSI under CO2 atmosphere. A two electron reduction wave was observed at ca. 1.7 V vs. SCE, which corresponds to the reduction of 1. Moreover, in the cathodic scan a new reduction peak at 2.00 V vs. SCE is also detected, which is ascribed to the electrochemical reduction of CO2 in the IL. The peak current value of this second reduction peak grows when the concen- tration of CO2 in the ionic liquid increases. In order to obtain the products 3 and 4, control potential electrolyses at 1.75 V vs. SCE under saturated CO2 atmosphere were performed in the above-mentioned electrolytic media with silver foil (a control potential electrolysis at 2.1 V vs. SCE was Fig. 4 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C on a silver electrode of a solution of 20 mM of 1 in PP13 TFSI (black line), EMIM TFSI (blue line) under nitrogen atmosphere. (11 kcal mol1) with respect to the glassy carbon electrode in EMIM TFSI and PP13 TFSI, respectively (Table 3, entries 1 and 2). Table 3 Cathodic peak potential (Epc in V), DEp ¼ |Epc  Epc/2| (in mV), scan rate: 0.5 V s1, concentration ca. 50 mM, charge transfer coef- ficient (a) for 1 in several solvents using silver as a working electrode at 25  C under nitrogen atmosphere Entry Solvent Epc (V) DEp (mV) a Number of electrons 1 EMIM TFSI 1.96 95 0.46 2.3 Fig. 5 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C on a silver 2 PP13 TFSI 1.66 130 0.37 1.9 electrode of 10 mM of 1 at different concentrations of CO2 in PP13 TFSI. 15120 | RSC Adv., 2019, 9, 15115–15123 This journal is © The Royal Society of Chemistry 2019 View Article Online Paper RSC Advances This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. Fig. 6 Cyclic voltammograms (scan rate 0.5 V s1) at 25  C showing controls of the control potential electrolysis of 1 at CO2 atmosphere in PP13 TFSI on Ag electrode (a) GC electrode (b) Ag electrode. Table 4 Results of electrocarboxylation of 1 to obtain R–COOH/Me R–COOH (Ibuprofen isolated yield) R–H Entry Solvent Eapplied C mol1 Yielda (%) Conversion rateb (%) Reagent recovery (%) (%) 1 EMIM TFSI 2.10 2.3 17 34 50 33 2 PP13 TFSIc 1.75 2.0 9 38 76 15 3 PP13 TFSId 1.75 2.5 82 85 3 15 R–COOMe (methylated Ibuprofen isolated yield) R–H Entry Solvent Eapplied C mol1 Yield (%) Conversion rate Reagent recovery (%) (%) 4 EMIM TFSI 2.10 2.3 18 35 49 33 5 PP13 TFSIc 1.75 2.0 8 35 77 15 6 PP13 TFSId 1.75 2.5 83 83 0 17 a Percent yield over isolated product. b Percent of Ibuprofen over consumed reactant. c PP13 TFSI commercially available (0.05% of water). d PP13 TFSI dried under vacuum and molecular sieves (less than 0.01% of water). performed in EMIM TFSI). The reduction processes were easily 4. Conclusions monitored by means of cyclic voltammetry with a silver elec- trode and a glassy carbon electrode (Fig. 6), showing the In conclusion, a description is presented of an efficient disappearance of 1. In all the cases Ibuprofen and its methyl- approach for producing high value compounds using CO2 as ated analogue (when iodomethane was added as electrophile) building block. The methodology employed is based on elec- were obtained with moderate to good yields (Table 4). As trochemical techniques and ILs, which allow eco-friendly previously mentioned, it should be noted that, for obtaining chemistry solutions to be used and maintain the aim of yields close to 100% the IL should be previously dried. The use offering a potential long-term strategy for using CO2 feedstocks. of commercial IL (#0.05% water content) also yields a 20% of The use of dried PP13 TFSI as electrolyte helps to overcome the protonated compound 2. main drawbacks associated with previous processes reported in Finally, the use of silver as a working electrode also allows the literature, where organic solvents, redox mediators, and the electrocarboxylation synthesis of Ibuprofen to be performed large quantities of supporting electrolytes are employed. It is in EMIM TFSI. Furthermore, the electrochemical potential important to highlight the economic feasibility and viability of required is lower than in carbon electrodes and within the replacing organic aprotic solvents that contain 0.1 M TBABF4 of electrochemical window of the IL. However, when electro- supporting electrolyte by ILs. Although the price of a single chemical synthesis is performed in EMIM TFSI, only 30% of 2 is experiment in IL is double that of DMF + 0.1 M of TBABF4, the obtained due to the acidity of the C2–H of the imidazolium fact that the IL can be recovered and reused in almost 80% at moiety. the end of the experiment makes this methodology highly viable and attractive. Moreover, changing the nature of the working This journal is © The Royal Society of Chemistry 2019 RSC Adv., 2019, 9, 15115–15123 | 15121 View Article Online RSC Advances Paper electrode, the synthesis, in terms of potential applied, is 17 A. S. R. Machado, A. V. M. Nunes and M. N. da Ponte, J. improved and allows the use of ionic liquids with a narrow Supercrit. Fluids, 2018, 134, 150–156. electrochemical window, such as imidazolium ionic liquids. 18 M. A. Scibioh and B. Viswanathan, Proc. Indian Natl. Sci. Controlled potential electrolysis of 1-chloro-(4-isobutylphenyl) Acad., 2004, 70, 407–462. This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. ethane under CO2 atmosphere allows Ibuprofen to be obtained 19 I. Reche, I. Gallardo and G. Guirado, RSC Adv., 2014, 4, in good yields and excellent conversion rates. This methodology 65176–65183. offers a new “green” route for the synthesis of different 20 R. Matthessen, J. Fransaer, K. Binnemans and D. E. De Vos, carboxylic acids that can be potential non-steroidal anti- Beilstein J. Org. Chem., 2014, 10, 2484–2500. inammatory drugs (NSAIDs) in a more environmentally 21 A. A. Isse, S. Gottardello, C. Durante and A. Gennaro, Phys. friendly way. Chem. Chem. Phys., 2008, 10, 2409–2416. 22 E. E. L. Tanner, C. Batchelor-McAuley and R. G. Compton, J. Open Access Article. Published on 14 May 2019. Downloaded on 12/10/2019 4:05:43 PM. Phys. Chem. C, 2016, 120, 26442–26447. Conflicts of interest 23 A. A. Isse, A. Galia, C. Belore, G. Silvestri and A. Gennaro, J. 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