Synthesis of novel triiodide ionic liquid based on quaternary ammonium cation and its use as a solvent reagent under mild and solvent-free conditions

1 Introduction

The goal of sustainable or green chemistry is to extend technical processes and their applications in utilizing chemicals with potentially eliminated or reduced hazards to the environment and humans [1,2]. The utilization of inherently safe or low-risk materials is favorable from an economic stand view and an ecological perspective [3]. Economic and social concerns make highly critical environmentally sustainable chemical processes, including clean organic reactions in the absence of noxious organic solvents [4]. Therefore, the industry has commenced embracing green chemistry practices, inclusive waste prevention rather than its treatment. Nowadays, the disposal of organic solvents in most industries, especially the pharmaceutical industry, is a significant problem and accounts for about 80% of their waste [5]. Therefore, solvents such as supercritical liquids, water, and ionic liquids in green synthesis have received much attention in recent times. Among the mentioned solvents, ionic liquids are a set of green solvents with unparalleled attributes, such as high thermal stability, scant vapor pressure, tunable polarity, recyclability, and immiscibility with some organic solvents compared to other solvents, which have a significant advantage [6,7,8,9,10,11].

One of the useful features of ionic liquids is their high polarity and ability to dissolve organic and inorganic compounds, elevating the rate of chemical processes and providing a higher selectivity than traditional solvents. For these reasons, they are a new alternative to volatile organic solvents in synthesizing organic compounds. Ionic liquids are inexpensive compounds that are straightforward to prepare and easy to recycle, and their attributes can be adjusted by switching ions or alkyl groups attached to cations. Due to the prominent benefits of room-temperature ionic liquids (RTILs) as an environmentally conducive reaction medium for chemical processes, much attention has now been paid to organic reactions consisting of ionic liquids [12,13,14,15,16,17,18,19], some of which halogenation reactions have been discussed [20,21,22,23,24,25,26]. Considering these leading properties, ionic liquids, especially RTILs, have become one of the most influential and widely used replacement solvents in industrial chemical processes. Furthermore, as they can be adjusted by switching the alkyl group or the anion connected to the cation, a wide range of ionic liquids with specific features can be synthesized [27,28,29,30].

Halogens are one of the most significant chemical and pharmaceutical compounds. Organohalogens are compounds generated by bacteria, fungi, diverse marine organisms, and plants and have been recognized as naturally occurring materials [31]. Many organohalogens have an exclusive place as solvents and pesticides, and play a critical role as intermediates in producing drugs, dyes, water treatment processes, dye-sensitized solar cells, and synthetic polymers, agrochemicals pigments, and photographic materials.

Regarding the value of green chemistry goals, here we introduce and synthesize a new and recoverable and inexpensive triiodide ionic liquid based on quaternary ammonium cation with extraordinary properties and excellent performance. Afterward, its application as a dual solvent reagent under mild conditions is investigated.

2 Experimental section

3 Results and discussion

Iodinated organic compounds are of great importance and have many applications; for example, they can be used as precursors or synthons in the synthesis of organic compounds mainly to form C–C and C–N bonds [32,33,34] and can also be utilized as contrast agents in medical diagnosis or radioactively labeled markers [35,36]. In the past, many iodization methods have been developed in molecular solvents, while in recent years, more attention has been paid to “greener” protocols [37,38,39]. However, iodination in IL media has gained less attention relative to fluorination or bromination [35,36,37,38,39,40].

This article introduces the synthesis, characterization, and reactivity of nonaromatic cation-based salt, N,N,N-triethyl-3-iodopropan-1-aminium triiodide 2, which can act both as a solvent and as a reagent in combination with H₂O₂ (35%) for the iodination of arenes. N-Alkylammonium ionic liquid 2 is a proton-free RTIL iodine analog with no measurable vapor pressure. Furthermore, 2 is a rare example of RTIL, which integrates the function of solvent and reagent [36]. Our synthesis of [N_2223I][I₃] is outlined in Scheme 1, path A. In the first step, the needed N,N,N-triethyl-3-iodopropan-1-aminium iodide 1 was generated from inexpensive triethylamine and 1,3-diiodopropane pursuit a modified literature method [41]. Under the solvent-free condition, this N-alkylation reaction was easily obtained with a high isolated yield (95%). At room temperature, the second step took place immediately (1 s), adding one equivalent molecular iodine under mechanical stirring to powdered N,N,N-triethyl-3-iodopropan-1-aminium iodide 1 exothermically formed the brown liquid N,N,N-triethyl-3-iodopropan-1-aminium triiodide 2. From Scheme 1, path A, it can be perceived that this method needs approximately an hour, while conventional methods take several days, so the reaction time is greatly reduced. It is important to note that when triethylamine was heated in boiling ethanol in the presence of 1,3-diiodopropane (Scheme 1, Path B), the formation of the bis(trimethylammonium) salt 3 was observed. Surprisingly, no product containing N,N,N-triethyl-3-iodopropan-1-aminium iodide 1 was detected. Adding molecular iodine to a stirring mixture of N ¹ ,N ¹ ,N ¹ ,N ³ ,N ³ ,N ³ -hexaethylpropane-1,3-diaminium diiodide in ethanol at room temperature formed the black solid N ¹ ,N ¹ ,N ¹ ,N ³ ,N ³ ,N ³ -hexaethylpropane-1,3-diaminium di triiodide 4. Compounds have been characterized by FTIR, ¹HNMR, ¹³CNMR, and UV-Vis spectroscopy (provided in the supplementary material).

Scheme 1

Synthesis pathway for the preparation of RTIL-2 and solid triiodide salt 4.

RTIL is miscible with polar organic solvents, such as chloroform, acetonitrile, and acetone, and insoluble in less polar solvents such as ethyl acetate, diethyl ether, toluene, and hexane. New ionic liquid, like ionic liquids containing PF₆, is immiscible with water. On the other hand, its precursor N,N,N-triethyl-3-iodopropan-1-aminium iodide is highly soluble in water, thus facilitating the efficient recovery of N,N,N-triethyl-3-iodopropan-1-aminium iodide, and the separation of iodinated products. This feature affirms the supremacy of this reagent. RTIL 2 is stable for several months at ambient temperature without loss of its activity.

RTIL 2 was then examined as an iodinating agent for a set of aromatic compounds. In initial experiments, N,N-dimethylaniline was used as a model substrate to evaluate suitable reaction conditions to prepare iodo compounds. A wide range of oxidizing agents was examined in RTIL 2 as solvent and reagent. As shown in Table 1, the best results are referred to as ceric ammonium nitrate (CAN) and H₂O (Entry 7).

In green chemistry, the best materials for oxidants can be oxygen or hydrogen peroxide because water is their only by-product. [42,40]. In this project, according to the goals of green chemistry and considering that after the completion of the iodination of aromatic compounds, the only by-product of the reaction is N,N,N-triethyl-3-iodopropan-1-aminium iodide 1, and this salt dissolves easily in the water resulting from the oxidation of hydrogen peroxide and separates from the reaction product, so the best choice in this reaction is hydrogen peroxide as oxidant. Thus, we applied hydrogen peroxide as the oxidant (Table 1). We observed that the reaction of N,N-dimethylaniline (1.0 mmol) with 1 mL of H₂O₂ (35%) in 1 mmol of RTIL 2 at 50°C proceeded to completion within 45 min (Table 2, Entry 3).

The progress of the reaction mixture led to the corresponding 4-iodo-N,N-dimethylaniline with excellent regioselectivity and excellent isolated yield (90%) (Table 3, Entry 1). This procedure worked successfully for the structurally different arenes. As can be perceived from the results listed in Table 3, all iodination substitution reactions with this system proceeded well. The reaction of 1,3-dimethoxybenzene was performed after 30 min to compose the mono-iodinated compound in a 95% isolated yield (Table 3, Entry 8). Anisole’s reaction needed more time, and 4-iodoanisole was the only reaction product obtained after 1 h (Table 3, Entry 11). Iodinations of N,N-dimethylaniline (Table 3, Entry 1) and N,N-diethylaniline (Table 3, Entry 2) were also performed in a short reaction time (∼50 min), and the mono-iodinated para isomers were generated in 90 and 88% isolated yields, respectively. The reaction of phenol took longer and was completed within 60 min to give 2,4,6-triiodophenol as the sole product of the reaction (Table 3, Entry 9). The iodination of N-phenylmorpholine produced 4-iodo-N-phenylmorpholine in 88% isolated yield as the only product after 40 min (Table 3, Entry 5). N ¹ ,N ¹ ,N ⁸ ,N ⁸ -Tetramethylnaphthalene-1,8-diamine was also iodinated within 1 h to produce the mono-iodinated product in 85% isolated yield, the only product of the reaction (Table 3, Entry 6). Afterward, we exerted these optimized conditions to N-phenyl-1-aza-15-crown-5. The reaction proceeded well and produced the mono-iodinated para isomer in excellent yield within a short reaction time (Table 3, Entry 10). Iodinations of p-toluidine, biphenyl-2-ol, and 2,2^′-(phenylazanediyl)diethanol were also studied. Isolation of 2-iodo-4-methylaniline in 93% (Table 3, Entry 7), 5-iodobiphenyl-2-ol in 90% (Table 3, Entry 4), and 2,2′-(4-iodophenylazanediyl)diethanol in 80% (Table 3, Entry 3) from the reaction compounds as the exclusive products of the reaction shows the high regioselectivity of the procedure, and also excellent chemoselectivity was observed for substrates with OH and NH functionalities, providing mono-iodinated derivatives as the major products, and no significant oxidation took place. The iodination of furan-2-carbaldehyde and benzonitrile under resembling reaction conditions was unsuccessful, and the mentioned materials were isolated intact after 48 h. The outcomes of this perusal are compiled in Table 3. The reactions that generate water-tolerant and hydrophobic products are disrupted and quenched by adding water. This even results in precipitation of the products as solids or oils, easily separated and rinsed with water and desiccated (either with Na₂SO₄ or in vacuo). The aqueous phase comprising very water-soluble 1 was easily concentrated in vacuo to recover 1, which then could be utilized to renew RTIL 2 with iodine (Scheme 1, path A). Therefore, it was recycled several times after completing the reaction, and the results were very desirable (Table 4). We declare no organic solvent in this method, and water is the only solvent used to extract and quench the mixtures at the end of the reaction. In other words, reactions leading to water-miscible products (Entries 4, 6) were extracted with Et₂O.

Table 3

RTIL 2 as the reagent and solvent-assisted iodination of aromatic compounds in the attendance of H₂O₂ (35%) at 50°C^a

Entry	Substrate	Product	Time (min)	Yield (%)b
1			45	90
2			50	88
3			40	80
4			30	90
5			40	88
6			40	85
7			30	96
8			30	95
9			60	84
10			25	91
11			60	84

^aAll products were designated by IR, ¹HNMR, and ¹³CNMR spectroscopic data, and melting points.

^bIsolated yields.

The precise mechanism for this reaction is not clear. In the possible mechanism, hypoiodous acid (HOI) is produced by the reaction of RTIL 2 with hydrogen peroxide. Then, the electrophile (iodonium ion) attacks the aromatic ring to synthesize the iodinated product [43] (Scheme 2). The presence of tetraalkyl ammonium iodide salt 1 and brominated products was confirmed using FTIR, ¹HNMR, and ¹³CNMR spectra at the end of the reaction.

Scheme 2

The plausible reaction mechanism for the iodination of aromatic compounds in the presence of RTIL 2 as the reagent and the solvent and H₂O₂ (35%).

4 Conclusion

According to the goals of green chemistry and its approach to using green solvents and compounds to reduce environmental pollution, this article presents a significant and mild method for iodination reaction utilizing ionic liquid 2 based on quaternary ammonium cation as a novel reagent and reaction medium. Based on data from the literature, we have, for the first time, reported a recoverable and inexpensive triiodide ionic liquid, and it is the first example that triiodide RTIL was used both as the green solvent and as a reagent in combination with H₂O₂ (35%) to produce corresponding iodo derivatives. The iodination was performed without the presence of any organic solvent, and water was the only extraction solvent. At the end of the reaction, the consumed reagent N,N,N-triethyl-3-iodopropan-1-aminium iodide was easily recycled.

The simplicity of the methodology, mild conditions, ease of product isolation, and the probability of IL recycling could make this process attainable in the future on the industrial scales. In addition to iodination, it can be utilized for various other organic transformations listed in due course.