Tunable Aryl Imidazolium Recyclable Ionic Liquid with Dual Brønsted–Lewis Acid as Green Catalyst for Friedel–Crafts Acylation and Thioesterification

Unique tunable aryl imidazolium ionic liquids successfully catalyzed Friedel–Crafts acylation and thioesterification in sealed tubes. These reactions can form a C−C bond and a C−S bond with high atom economy. Ionic liquids exhibited high activity and catalyzed essential reactions with good to excellent yields while retaining their catalytic activities for recycling.


Introduction
Ionic liquids outperform organic solvents in industrial processes and are considered as an eco-friendly choice to the broad scope of the organic reactions [1][2][3][4][5][6]. They are important green solvents that exhibit high thermal stability, recovery, and recycling. They are also a new class of solvents that are expected to be increasingly used by the chemical industry in the next few years, replacing volatile organic solvents. Owing to their low volatility, non-flammability, and thermal stability, ionic liquids can be applied in many operations. Most ionic liquids, such as imidazolium, comprise an organic or inorganic anion and a quaternary ammonium cation [7][8][9][10]. Because they are hugely tunable and have remarkable properties, they have become a crucial part in synthesis and catalysis. Most of the interest in ionic liquids concentrates on their ability to change considerably the reactivity of dissolved solutes. The properties of ionic liquids have caused them to be identified as designer solvents, including task specific ionic liquids [11,12]. A comprehensive understanding of the physical characteristics of ionic liquids can increase their industrial use [13]. Ionic liquids have been analyzed owing to their many applications in organic synthesis, analytical chemistry, electrochemistry, separation chemistry, separation technology, polymers, fiber optics, pH sensors, and others [14,15].

Results and Discussion
Initial studies of 2a and 3a determined the optimal reaction conditions ( Table 1). The study of dual Brønsted-Lewis acidic ionic liquids 1a, 1b, 1c, and 1d of Figure 1 suggested that 1d was the best catalyst of Friedel-Crafts acylation, providing the product 4a in 74% yield (Table 1, entries [1][2][3][4] [37,38]. Increasing the temperature to 100 • C and 120 • C with 1d afforded 4a in 74% and 71% yields, respectively ( Table 1, entries [5][6]. Lowering the concentration of 1d to 0.9 equivalent led to higher yield (78%, In general, electronic effects and polarity of solvents play important roles in the outcomes of the product for Friedel-Crafts reaction. The changing the connected carbon and oxygen atoms were accomplished through para selective functionalization of benzoic acid in the presence of palladium catalyst [16][17][18][19]. The aromatic ketones of Friedel-Crafts acylation are a fundamental mediator in a broad range, such as pharmaceutical dyes, fragrances, and agrochemicals [20], and are convenient for use in the synthesis of poly (4-vinyl pyridine)-triflic acid, indium triflate [21,22], perfluoroalkane sulfonic acidic resin is an acid catalyst with catalytic activity for many reactions giving high selectivity. One major drawback of this catalyst is its inefficient swelling by aprotic organic solvents, which generally leads to low reaction rates and others [23]. Iron (III) chloride earns wider acceptance as a useful Lewis acid in Friedel-Crafts acylation [24]. The most exciting feature of our synthesized ionic liquids have an important role in Friedel-Crafts acylation. Previous investigations have reported that ionic liquids exhibit the dual Brønsted and Lewis acidic property, the halogen-free Brønsted-Lewis acidic ionic liquids were synthesized and exploited to catalyze the esterification of caprylic acid with methanol. The novel multifunctional MCM-41 as Brønsted-Lewis acidic ionic liquids were prepared and tested for their catalytic activities in one-pot three-component Mannich reactions [25][26][27]. Benzoylation of anisole catalyzed by metal triflate and chloroindate (III) by Lewisacid ionic liquid were used in Friedel-Crafts reaction [28,29]. The consolidation of sp 3 alkyl and sp 2 aryl substituents at the nitrogen atoms of the imidazolium origin allowed a far greater variety of ionic liquids [30]. These ionic liquids have an sp 2 hybridized carbon atoms as an N-substituted heterocycle are synthesized as a novel type of ionic liquids is a renowned catalyst which is moisture insensitive and stable at room temperature, use for a variety of organic transformations, including Friedel-Crafts acylation reactions. The electron-withdrawing group of the aryl ring allows easier deprotonation of imidazolium for forming a stronger Brønsted acid.
Thioesters are important molecules for organic synthesis and are obtained by coupling aldehydes and sulfur surrogates recently [31]. Kita and co-workers described the formation of thioesters from aldehydes [32] and specific pentafluorophenyl disulfide [33]. Takemoto and coworkers reported the expensive carbene-promoted coupling reaction of thiols and aldehydes [34]. Bandgar and co-workers developed that Dess-Martin periodinane and NaN3 promoted to synthesize thio-esters with aldehydes and aryl thiols [35]. Lee and co-workers demonstrated that FeBr2 is able to catalyze synthesis of thioesters from thiols, aldehydes and tert-butyl hydro peroxide (TBHP) in water [36].

Friedel-Crafts Acylation
The scope of Friedel-Crafts reaction with various aryl alkanes and acyl chlorides under optimized reaction conditions was investigated ( Table 2, entries 1-8). The Friedel-Crafts reactions with aryl alkanes 2a and different acyl chloride (3b-3c) under standard conditions were carried out, and the desired products 4b and 4c were isolated in 73% and 68% yields ( Table 2, entries 1,2). Under the same reaction conditions, the Friedel-Crafts reaction in the presence of 2b and 3a produced 4d in 83% yield (Table 1, entry 3). The reaction proceeded very smoothly with 2b and 3b under the above conditions to yield the compound 4e with a 79% yield ( Table 2, entry 4). Acyl chloride 3c reacted with 2b to afford the corresponding product 4f in 89% yield (Table 2, entry 5). Aryl alkane 2c and acyl chloride 3a were coupled under similar reaction conditions to obtain the product 4g in 81% yield (Table 2, entry 6). When the reaction was performed using 2c and 3b, the product 4h was afforded in 71% yield (Table 2, entry 7). Product 4i was furnished in 70% yield using 2c and 3c (Table 2, entry 8). While doing Friedel-Crafts acylation, HCl did not affect the reaction, so could not consider to remove HCl from ionic liquid. It is possible to remove HCl from an ionic liquid by using a high vacuum or suction pump.

Friedel-Crafts Acylation
The scope of Friedel-Crafts reaction with various aryl alkanes and acyl chlorides under optimized reaction conditions was investigated ( Table 2, entries 1-8). The Friedel-Crafts reactions with aryl alkanes 2a and different acyl chloride (3b-3c) under standard conditions were carried out, and the desired products 4b and 4c were isolated in 73% and 68% yields ( Table 2, entries 1,2). Under the same reaction conditions, the Friedel-Crafts reaction in the presence of 2b and 3a produced 4d in 83% yield ( Table 1, entry 3). The reaction proceeded very smoothly with 2b and 3b under the above conditions to yield the compound 4e with a 79% yield ( Table 2, entry 4). Acyl chloride 3c reacted with 2b to afford the corresponding product 4f in 89% yield (Table 2, entry 5). Aryl alkane 2c and acyl chloride 3a were coupled under similar reaction conditions to obtain the product 4g in 81% yield ( Table 2, entry 6). When the reaction was performed using 2c and 3b, the product 4h was afforded in 71% yield (Table 2, entry 7). Product 4i was furnished in 70% yield using 2c and 3c (Table 2, entry 8). While doing Friedel-Crafts acylation, HCl did not affect the reaction, so could not consider to remove HCl from ionic liquid. It is possible to remove HCl from an ionic liquid by using a high vacuum or suction pump.
To further develop a recyclable catalytic system, the recycling of the 1d was inspected under the optimized conditions ( Figure 2a). After reaction finished, diethyl ether was added. The ionic liquid 1d was recovered from water layer and dried for the next reaction under vacuum. For the first run, the activity of ionic liquid 1d remained same yield (78%). In the subsequent second (76%), third (66%), fourth (69%), and fifth (67%) cycles, the desired product was still reached with 100% conversion, when reaction was monitored on TLC plate, the desired product saw without any side product (Figure 2b).
To further develop a recyclable catalytic system, the recycling of the 1d was inspected under the optimized conditions ( Figure 2a). After reaction finished, diethyl ether was added. The ionic liquid 1d was recovered from water layer and dried for the next reaction under vacuum. For the first run, the activity of ionic liquid 1d remained same yield (78%). In the subsequent second (76%), third (66%), fourth (69%), and fifth (67%) cycles, the desired product was still reached with 100% conversion, when reaction was monitored on TLC plate, the desired product saw without any side product (Figure 2b).

Thioesterification
Initially, benzaldehyde 5a and 1-dodecanethiol 6a were selected as the model substrates to determine the optimized reaction conditions and the results are summarized in Table 3. We first examined the source of the ionic liquids 1a-1d (0.025 equivalent) in presence of TBHP as a oxidant at 120 °C (Table 3, entries 1-4), and 1d was the best catalyst of thioesterification providing the product 7a in 70% yield (Table 3, entries 1-4). Decreasing the temperature to 100 °C and increasing the

Thioesterification
Initially, benzaldehyde 5a and 1-dodecanethiol 6a were selected as the model substrates to determine the optimized reaction conditions and the results are summarized in Table 3. We first examined the source of the ionic liquids 1a-1d (0.025 equivalent) in presence of TBHP as a oxidant at 120 • C ( Table 3, entries 1-4), and 1d was the best catalyst of thioesterification providing the product 7a in 70% yield (Table 3, entries 1-4). Decreasing the temperature to 100 • C and increasing the temperature to 140 • C with 1d afforded 7a in similar yields (Table 3, entries 5-6). Decreasing the concentration of 1d to 0.010 equivalent led to lower yield (68%, Table 1, entry 7), while increasing it to 0.030 equivalent reduced the reaction yield (61%, Table 1, entry 8).

Thioesterification
Initially, benzaldehyde 5a and 1-dodecanethiol 6a were selected as the model substrates to determine the optimized reaction conditions and the results are summarized in Table 3. We first examined the source of the ionic liquids 1a-1d (0.025 equivalent) in presence of TBHP as a oxidant at 120 °C (Table 3, entries 1-4), and 1d was the best catalyst of thioesterification providing the product 7a in 70% yield (Table 3, entries 1-4). Decreasing the temperature to 100 °C and increasing the temperature to 140 °C with 1d afforded 7a in similar yields (Table 3, entries 5-6). Decreasing the concentration of 1d to 0.010 equivalent led to lower yield (68%, Table 1, entry 7), while increasing it to 0.030 equivalent reduced the reaction yield (61%, Table 1, entry 8). Table 3. Optimized condition of thioesterification.
With these optimized reaction conditions in hand, the scope of the substrates was then studied. The results are summarized in Table 4. A variety of alkyl thiols and aromatic thiols were conducted with aromatic and alkyl aldehydes to afford the corresponding thioesters in good to excellent yields. Aromatic aldehydes bearing electron-donating and electron-withdrawing substituents are all suitable for catalysis. Aldehyde reacted with thiol 6b and 6c to give corresponding product 7b in 88% and 7c in 55% respectively. It is important to note that this system shows good functional group tolerance; chloro (Table 4, products 7d, 7e and 7f) are tolerated by reaction condition employed. Aldehydes bearing electron donating substituents underwent thioesterification with alkyl and aryl thiols to give desired product (Table 4, products 7g and 7h). Alkyl thiols were also reacted with alkyl aldehydes to give the corresponding thioesters (Table 4, products 7i, 7j, 7k, and 7l). Table 4. Ionic liquids 1d catalyzed coupling reaction with aldehydes 5a-5e and thiols 6a-6c without solvent. and 7c in 55% respectively. It is important to note that this system shows good functional group tolerance; chloro (Table 4, products 7d, 7e and 7f) are tolerated by reaction condition employed. Aldehydes bearing electron donating substituents underwent thioesterification with alkyl and aryl thiols to give desired product (Table 4, products 7g and 7h). Alkyl thiols were also reacted with alkyl aldehydes to give the corresponding thioesters (Table 4, products 7i, 7j, 7k, and 7l). In this method, the recovery of ionic liquid 1d ranges from 63-70% yields. The catalytic activity was examined by thioesterification of thiols at 120 °C for 1 h (Figure 4a). The results are presented in (Figure 4b). Ionic liquid was recovered and reused up to five times with only slightly decreased catalytic activity.
In this method, the recovery of ionic liquid 1d ranges from 63-70% yields. The catalytic activity was examined by thioesterification of thiols at 120 • C for 1 h (Figure 4a). The results are presented in (Figure 4b). Ionic liquid was recovered and reused up to five times with only slightly decreased catalytic activity.
Based on the above experimental results, a plausible mechanism is proposed in Figure 5. When 1d is reacted with TBHP, and t-BuOO · radical is generated at the time. Initially benzaldehyde reacted with ionic liquid 1d, which would lead to intermediate 3. Then thiols react with intermediate 3 to give 4. A hydrogen atom is then abstracted from aldehyde to give an acyl radical. Further t-BuOO · radical reacted with 4 to give complex 5 and then hydroxyl radicle II Reacts with 5 to give the final product 6.
Based on the above experimental results, a plausible mechanism is proposed in Figure 5. When 1d is reacted with TBHP, and t-BuOO · radical is generated at the time. Initially benzaldehyde reacted with ionic liquid 1d, which would lead to intermediate 3. Then thiols react with intermediate 3 to give 4. A hydrogen atom is then abstracted from aldehyde to give an acyl radical. Further t-BuOO · radical reacted with 4 to give complex 5 and then hydroxyl radicle II Reacts with 5 to give the final product 6.

Materials and Methods
The reactions were conducted in flame-dried glassware, under the nitrogen atmosphere. Acetonitrile and dichloromethane were purified and dried from a safe purification system containing activated Al2O3. All reagents obtained from commercial sources were used without purification unless otherwise mentioned. Flash column chromatography was carried out on Silica Gel 60. TLC

Conclusions
The designed ionic liquid 1d were successfully catalyze the Friedel-Crafts acylation reaction and thioesterification reaction. It provides good to excellent yield in both the reactions under optimal conditions. The ionic liquid 1d exhibits the dual Brønsted and Lewis acidic property. The catalyst showed high atom economy, high thermal stability, and could be recycled with minor loss in activity and also moisture insensitive. The catalyst shows some limitations, which exhibited good solubility in many organic solvents and deionized water, but not in hexane. Funding: This research was funded by National Chung Hsing University, and Chia Nan University of Pharmacy and Science.