Synthesis of orthoaminocarbonitrile tetrahydronaphthalenes catalyzed by butyl-3-methylimidazolium hexafluorophosphate ionic liquid base catalyst

Abstract In this research, the treatment of cyclohexanone, malononitrile, and aromatic aldehydes was carried out for the successful synthesis of orthoaminocarbonitrile tetrahydronaphthalenes by using butyl-3-methylimidazolium hexafluorophosphate as a base catalyst. In this protocol, the target products were obtained in high to excellent yields between 85% and 95% and short reaction times between 10 and 20 min under mild conditions. All products were identified by the melting points, FT-IR, and 1H NMR techniques. Graphical abstract

Salt in a liquid condition is known as an ionic liquid. The essential advantages of ionic liquids include non-volatility. Furthermore, applications of ionic liquids as solvents or catalysts in multicomponent reactions are very important because they have low vapor pressure and are biodegradable and they have a broad array of applications. They are strong solvents that can also serve as electrolytes due to their low vapor pressure, salts that are liquid at near-ambient temperatures are essential for electric battery applications. [24] Recently, it was reported a chemical reaction for the synthesis of orthoaminocarbonitrile tetrahydronaphthalenes under mild conditions. [19] Also, Zhang et al. in 2015 synthesized D-glucopyranosyl bromide. [16] In this research, the authors attempt to examine the performance of butyl-3methyl imidazolium hexafluorophosphate as a homogeneous catalyst in multicomponent reactions with high efficiency and short reaction times. The reaction of cyclohexanone with malononitrile followed by the addition of aromatic aldehydes and malononitrile yielded one-pot ortho aminocarbonitrile tetrahydronaphthalenes under mild conditions.

Results and discussion
This research describes the multicomponent treatment of cyclohexanone, malononitrile, and aromatic aldehydes in a process to yield orthoaminocarbonitrile tetrahydronaphthalenes with excellent efficiency and short reaction times. This reaction was carried out in the presence of butyl-3-methylimidazolium hexafluorophosphate as an effective homogeneous catalyst (Scheme 1).
The various solvents, catalysts, and temperatures were investigated to determine the best conditions for this procedure. The reaction was tested at ambient temperatures ( Table 1) and under reflux conditions ( Table 2, entry 1) for the first time, but the product yield was low. Then, various catalysts were used in the reaction and the related results are indicated in Table 2. A minimal amount of product was observed in the presence of an acidic catalyst such as; HCl and P-TSA ( Table 2, entries 2 and 3). The reaction efficiencies increased using the basic catalysts and ionic liquids such as; BMIM.BF 4 , BMIM.PF 6 , Et 3 N, guanidine, morpholine, and NaOH (Table 2). Among them, the BMIM.PF 6 ionic liquid significantly increased the reaction interval and decreased the reaction time.
Also, the reaction was tested in a variety of solvents including ethanol, chloroform, dichloromethane, methanol, and acetonitrile to find the optimal reaction conditions. It was found that the ethanol solvent is the best convenient solvent for this reaction. Thus, the reactions were investigated in ethanol under reflux and room temperature conditions by using an ionic liquid as a catalyst. It was found that the reaction using BMIM.PF 6 ionic liquid under reflux conditions has the best results.   After optimization of the reaction conditions, the best conditions for the synthesis of orthoaminocarbonitrile tetrahydronaphthalene from cyclohexanone (1 mmol), malononitrile (2 mmol), and benzaldehyde (1 mmol) by using BMIM.BF 4 catalyst in ethanol solvent under reflux conditions at 10-20 min were considered. As a result, orthoaminocarbonitrile tetrahydronophthalene derivatives were synthesized in 85-95% yields at 10-20 min under reflux conditions (Table 3). Table 4 shows the results of the comparison of the performance of the BMIM.PF 6 catalyst with the applications of the stated catalysts. The BMIM.PF 6 catalyst outperforms the other used catalysts as can be seen in Table 4, entry 5. The BMIM.PF 6 as a hydrophobic and water-insoluble ionic liquid produced the best results in 95% efficiency at 10 min.
A plausible reaction mechanism for the synthesis of tetrahydronaphthalene is shown in Scheme 2. At first, the butyl-3-methylimidazolium hexafluorophosphate as a base catalyst causes the acidic hydrogen separate from malononitrile. Then, the resulting carbanion is attacked by the carbonyl group of cyclohexanone, and the A intermediate

Experimental
All of the chemical ingredients and solvents used in this study were provided by Merck and Aldrich Chemical Companies. The starting materials including cyclohexanone, aromatic aldehyde, and BMIM.PF 6 were purchased from Sigma and the malononitrile and ethanol from Merck Chemical Company. The IR spectra were obtained as KBr pellets on a Perkin Elmer 781 spectrophotometer and on an Impact 400 Nicolet FT-IR spectrophotometer. The 1 H NMR spectra were recorded in DMSO-d 6 solvents on a Broker DRX-400 spectrometer with tetramethylsilane (TMS) as the internal reference. Melting points were obtained with a Yanagimoto micro melting point and uncorrected. Determination of the substrate and reaction monitoring was accomplished by TLC on silica-gel polygram SILG UV 254 plates (from Merck Company).

General procedure for the synthesis of orthoaminocarbonitrile tetrahydronaphthalenes
In a 50 mL flask with a circular bottom, cyclohexanone (0.1 mL, 1 mmol) and malononitrile (0.06 g, 1 mmol) in 5 mL of ethanol solvent were mixed to make orthoaminocarbonitrile under reflux conditions. After 10 min, the reaction mixture was mixed with 0.3 mmoles of butyl-3methylimidazolium hexafluorophosphate ionic liquid (0.06 mL, 0.3 mmol), aromatic aldehyde (1 mmol), and malononitrile (0.06 mg, 1 mmol). Thin layer chromatography (TLC) is used to determine the response of the reaction. When the reaction was completed, then cooled to room temperature, filtered, and rinsed in a mixture of distilled water and ethanol (1:1 ratio). The crude products were recrystallized in ethanol solvent to give the pure products. The   products were characterized by spectroscopic data such as; FT-IR, 1 H NMR, and the melting points of known compounds are compared with authentic samples; [2,15,21,25,26] the related data are reported in the Supporting Information.

Conclusions
In this protocol, cyclohexanone, malononitrile, and aromatic aldehydes were treated together to produce the orthoaminocarbonitrile tetrahydronaphthalenes. The butyl-3methylimidazoliumhexafluorophosphate ionic liquid as a base homogeneous catalyst was employed in this reaction as an effective, convenient, and basic homogeneous catalyst to yield the products in high to excellent efficiency and minimal reaction times. In addition to the simplicity of the reaction and workup, the thermal stability and non-volatility are two advantages of this low vapor pressure ionic liquid as a catalyst. Furthermore, to improve the reaction conditions, an attempt was made to use ethanol as a green solvent as a novelty in this work.
Full experimental details are included in the IR and 1 H NMR spectra. This material can be found via the "Supplementary Content" section of this article's webpage.

Disclosure statement
Ionic liquids (ILs) have engrossed comprehensive research concerns as environmentally safe solvents due to their particular characteristics such as indiscoverable vapor pressure, vast liquid range, non-inflammability, and excellent thermal stability. Ionic liquids have been extensively applied in reactions as catalysts.
In this study, orthoaminocarbonitrile tetrahydronaphthalene compounds were synthesized using butyl-3-methylimidazolium hexafluorophosphate as a homogeneous base catalyst in high efficiency and short reaction time. This reaction was carried out through a multicomponent reaction between cyclohexanone, malononitrile, and aromatic aldehydes under mild conditions.

Funding
The present work was funded by the University of Kashan [159148/91].