An Efficient Method for the Production of Cyclohexylamine from Cyclohexanone and Ammonia over Cu-Cr-La/γ-Al₂O₃

Abstract

The reductive amination of cyclohexanone with ammonia over Cu-Cr-a/γ-Al₂O₃ was investigated. It was found that a proper solvent with high solubility of ammonia and 4Å molecular sieves for the elimination of generated water contributed to the formation of cyclohexylamine in the premixing process. In addition, the addition of ammonia in the fixedbed reactor could obviously improve the conversion of cyclohexanone to cyclohexylamine. Finally, reaction conditions including reaction temperature, hydrogen pressure and charging rate of the premix were optimized. Under the optimized conditions, cyclohexylamine was obtained in 83.06% yield.

INTRODUCTION

Amines and their derivatives served as one of the most important raw materials and always were employed for the synthesis of herbicides, insecticides, pharmaceuticals, corrosion inhibitors, plastics and rubber chemicals.1−4 Recently, the reductive amination of appropriate carbonyl compounds was the most environmental benign method to yield amines and thus attracted tremendous attentions. Accordingly, the related reports kept emerging as well. As a common industrial intermediate, the production of cyclohexylamine (CyNH2) was also a hotpot.5−12 It was traditionally produced by amination of cyclohexanol or cyclohexanone. For example, Poppe et al.13 have reported the production of cyclohexylamine with ammonium formate as ammonia source over Pd/C and 68% of yield was obtained. Ramachandran et al.14 and Burkhardt et al.15 respectively employed 5-ethyl-2-methylpyridine and ammonia borane for the reductive amination of cyclohexanone. Though the yield of cyclohexylamine was above 75%, the recycling of these catalysts was also an obstacle. HY or Hβ was applied for this reductive amination as well. However, only 19% of cyclohexylamine yield was achieved.16 Undoubtedly, these tedious work-up procedures or the poor selectivity restricted the development of CyNH2. It was very imperative to further improve the CyNH2 selectivity.

In this work, a serial of catalysts are employed for the reaction of cyclohexanone and ammonia in a fixed-bed reactor, and Cu-Cr-La/γ-Al2O3 exhibited the excellent performance. Meanwhile, in order to improve the selectivity of CyNH2, reaction conditions and premixing process were investigated. Based on aforementioned results, the possible reaction mechanisms were proposed.

 

EXPERIMENTAL

4Å molecular sieves were provided by The Catalyst Plant of Nankai University, Tianjin, PR China. Commercially available reagents and solvents were used without further purification.

The Preparation of Catalysts

Cu-Cr-La/γ-Al2O3 catalysts in this study were prepared by coprecipitation-kneading method. The details were briefly described as follows. Cu(NO3)2·3H2O (38.05 g), Cr(NO3)3·9H2O (19.23 g) and La(NO3)3·6H2O (7.79 g) were all dissolved in 400 ml of deionized water. In addition, Na2CO3 (29.38 g) was dissolved in 400 ml of deionized water. These two aqueous solutions were added simultaneously into a beaker containing 200 ml of deionized water under mechanical stirring. In this period, the pH of the suspension was maintained around 7.5-8.0. After aging for another 1 h, the mixture was filtered and the residue was washed with deionized water until no nitrate anion was left. Then, the samples were dried at 110 ℃ for 6 h and grind up into powders. Afterwards, the powders were kneaded with a mixture of pseudo-boehmite (57.55 g) and 50 ml, 2 wt % nitric acid. The mixture was molded into Φ3 bars by an extruder. The obtained catalysts were dried at 110 ℃ for 6 h, calcined at 500 ℃ for 4 h and activated at 240 ℃ for 4 h in a hydrogen steam (1.0 MPa) for later use.17−19 Other catalysts such as Ni/γ-Al2O3, Co/γ-Al2O3, Cu/γ-Al2O3, Cu-Cr/γ-Al2O3, Cu-Cr-Fe/γ-Al2O3, Cu-Cr-Mn/γ-Al2O3 and Cu-Cr-Zn/γ-Al2O3 were prepared as a similar approach.

4A molecular sieves were activated by calcination at 400 ℃ for 4 h in a muffle furnace. Afterwards, they were cooled down to ambient temperature and transferred to a drier before use.

Catalytic Reaction

The reductive amination of cyclohexanone with ammonia was carried out in a fixed-bed reactor consisting of a stainless steel tube with an inner diameter of 15 mm and a length of 660 mm inside a vertical furnace with a temperature controller. 40 ml of catalysts were placed in the middle of the tube. A solution of 10 wt % cyclohexanone in methanol and a certain amount of 4A molecular sieves were placed in a 100 ml one-necked flask fitted with magnetic stirrer. Cooled by ice bath, ammonia was dissolved into the mixture as much as possible. The resulting mixture was stirred for another 2 h at 0-5 ℃. Then the supernatant was pumped into the fixed-bed reactor at a speed of 0.2 ml/min. The obtained reaction mixture were analyzed every 3 h by GC equipped with a 30 m SE-54 capillary column and the components were confirmed on a GC-MS instrument equipped with a 30 m HP-5 capillary column.

 

RESULTS AND DISCUSSION

Catalyst Selection

Initially, a serial of catalysts including Ni/γ-Al2O3, Co/γ-Al2O3, Cu/γ-Al2O3, Cu-Cr/γ-Al2O3, Cu-Cr-Fe/γ-Al2O3, Cu-Cr-Mn/γ-Al2O3, Cu-Cr-Zn/γ-Al2O3 and Cu-Cr-La/γ-Al2O3 were employed for the reductive amination of cyclohexanone with ammonia and the results were summarized in Table 1. It was found that Cu-Cr-La/γ-Al2O3 displayed the best catalytic performance, which was accordance with the results Sun et al. reported20 (Sun et al., 2011), so this catalyst was used for the following research.

Table 1.Reaction conditions: 180 ℃, 3.0 MPa H2, Charging rate: 0.2 ml/min of the premix, solvent: methanol.

Reaction Mechanism

Subsequently, the reaction mechanism was investigated. When this reaction was proceeded using Cu-Cr-La/γ-Al2O3, a range of byproducts, including cyclohexanol (Cyol), 2-cyclohexylcyclohexanol (Cy-cyol) and dicyclohexylamine (Dicy) were detected except for CyNH2. So the improvement of CyNH2 selectivity was still an obstacle.

Referring to the mechanism for reductive amination of cyclohexanone with 1,6-diaminohexane,21 we proposed the possible reaction route for this reaction (Fig. 1). Initially, the nucleophilic addition of ammonia to cyclohexanone was carried out and then followed by the dehydration to yield cyclohexylimine, reversibly. Subsequently, CyNH2 could be obtained through the hydrogenation of cyclohexylimine. The formed CyNH2 would react with cyclohexanone to produce N-cyclohexylcyclohexylimine (Cy-Ncy), which was further hydrogenated to form Dicy. Meanwhile, cyclohexanol (Cyol) was produced with the direct hydrogenation of cyclohexanone. It also lowered the selectivity of CyNH2. Besides, the aldol condensation of cyclohexanone was preceeded on the acid sites of Cu-Cr-La/γ-Al2O3 and Cy-cyol might be generated. Therefore, the selectivity of CyNH2 would be further decreased. Moreover, two other byproducts, aniline and N-cyclohexylaniline, reported by Becker et al. (2000) were not detected in our study. This was probably due to different catalysts and reaction conditions in our work.

Figure 1.Possible reaction route of amination of cyclohexanone with ammonia.

Influences of Reaction Parameters in the Premixing Process

As indicated in Fig. 1, the reaction of cyclohexanone and ammonia to form cyclohexylimine was crucial to enhance the selectivity of CyNH2. As this reaction was reversible, the increase of cyclohexanone would undoubtedly improve the formation of cyclohexylimine. However, the excess cyclohexanone would also suffer from amination with the obtained CyNH2, direct hydrogenation or aldol condensation. The corresponding by-products were followed as well. So it was important to convert cyclohexanone into cyclohexylimine for the improvement of CyNH2 selectivity and a premixing process prior to this reaction in the fixed-bed reactor was investigated.

Solvent: Since the aforementioned reaction is reversible, the addition of ammonia would certainly prompt this reaction to shift right. The proper solvent with satisfied ammonia solubility was required. Therefore, three solvents including cyclohexanone, dioxane and methanol were employed for this reaction and the results were summarized in Table 2.

Table 2.Reaction conditions: 180 ℃, 3.0 MPa H2, Charging rate: 0.2 ml/min of the premix.

As shown in Table 1, when this reaction was carried out in cyclohexanone, only 1.46% of CyNH2 selectivity was obtained. Obviously, the poor ammonia solubility in cyclohexanone inhibited the formation of CyNH2 and excess cyclohexanone would be directly hydrogenated into Cyol. It was the reason why the poor CyNH2 selectivity was obtained with cyclohexanone.

When dioxane and methanol were employed, the selectivity of CyNH2 were 28.21% and 46.26%, respectively. The conversion of cyclohexanone basically kept consistent. Meanwhile, methanol also resulted into 21.73% of Dicy selectivity, which was lower compared with dioxane. We speculated that the excellent ammonia solubility in methanol always contributed to the conversion of cyclohexanone into CyNH2. Thus, methanol was selected as the solvent for amination of cyclohexanone with ammonia.

Molecular sieves: It was well known that the reaction of cyclohexanone with ammonia to produce cyclohexylimine was followed by the formation of H2O. So the removal of H2O would be in favor of right shift of this equilibrium.

During the synthesis of Schiff base, the generated water is normally removed by azeotropic distillation or vacuum distillation. However, both ammonia and cyclohexanone would be removed as well by these two methods. Therefore, commercially available 4Å molecular sieves were picked out for this dehydration. The obtained results were summarized in Table 3.

Table 3.Reaction conditions: 180 ℃, 3.0 MPa H2, Charging rate: 0.2 ml/min of the premix, ammonia in the fixed-bed reactor: 8 L/h.

With the increase of molecular sieves amount, the quantity of Cyol and Dicy presented an obvious decrease. However, the selectivity of CyNH2 dramatically increased. The reason might be attributed to the right shift of this equilibrium for the removal of H2O. When 4Å molecular sieves came up to 30 wt % of cyclohexanone, the selectivity of CyNH2 reached a high level, and continuously increasing 4A molecular sieves did not have obvious impact on this reaction. Thus, 30 wt % of molecular sieves (based on cyclohexanone) were used in the premixing process.

Influences of Reaction Conditions in the Fixed-bed Reactor

Reaction temperature: Fig. 2 clearly indicated that with the increase of reaction temperature, the conversion of cyclohexanone basically kept unchanged. However, the selectivity of CyNH2 went up at first, and then lowered down after 180 ℃, which were exactly opposite to the selectivity of Dicy. So it could be concluded that the enhanced temperature might facilitated the reaction between CyNH2 and cyclohexanone. This results were in accordance with the report by Becker et al. Thus, 180 ℃ was selected as the optimum reaction temperature.

Figure 2.Influence of temperature on amination of cyclohexanone with ammonia.

Hydrogen pressure: As shown in Fig. 3, the hydrogen pressure played a noticeable role on the reaction. With the enhancement of hydrogen pressure, the conversion of cyclohexanone rose from 88.7% to 99.0%. In contrast to Cyol and Dicy, the selectivity of CyNH2 increased firstly with a peak at 3.0 MPa and then decreased. We speculated that the high hydrogen pressure might be in favor of reaction (1) compared with reaction (2) and (3). The majority of cyclohexanone was consumed in reaction (1) to yield CyNH2. Correspondingly, the selectivity of Cyol and Dicy both decreased. But when hydrogen pressure increased to 4.0 MPa, parts of cyclohexanone would be directly hydrogenated into Cyol. In addition, Cy-N-cy obtained from cyclohexanone and CyNH2 was similarly converted into Dicy. Therefore, the selectivity of CyNH2 would be decreased. On the basis of the analysis above, 3.0 MPa was selected as the optimum hydrogen pressure.

Figure 3.Influence of hydrogen pressure on amination of cyclohexanone with ammonia.

Charging rate of the premix: Subsequently, the different charging rate of the premix was used to enhance the conversion of cyclohexanone and the selectivity of CyNH2. It was found that when the charging rate rose from 0.1 ml/min to 0.8 ml/min, the conversion of cyclohexanone decreased from 99.0% to 60.6%. The increase of weight hourly space velocity (WHSV) of cyclohexanone shortened the residence time, so that the obtained CyNH2 did not have enough time to be consumed to produce Dicy and the selectivity of CyNH2 would be increased. Considering the conversion of cyclohexanone and the selectivity of CyNH2, 0.2 ml/min was chosen as the optimum charging rate of the premix.

Ammonia in the Fixed-bed Reactor

It was obvious from Table 2 that although NH3 was added to the solution of cyclohexanone in methol as much as possible, quite high proportion of Cyol and Dicy remained in the product. It implied that more ammonia was required in the fixed-bed reactor. The obtained results were summarized in Table 4.

Table 4.Reaction conditions: 180 ℃, 3.0 MPa H2, Charging rate: 0.2 ml/min of the premix.

With the addition of ammonia in the fixed-bed reactor, the selectivity of CyNH2 increased. In contrast, the selectivity of Cyol and Dicy both decreased. The reason had been illustrated in our previous analysis. However, further increase of ammonia would give rise to the difficulty for operation, so ammonia was pumped into the fixed-bed reactor at a speed of 10 L/h.

 

CONCLUSIONS

The premixing process had an important effect on the reductive amination of cyclohexanone with ammonia over Cu-Cr-La/γ-Al2O3 catalyst. The application of methanol could efficiently dissolve NH3 and the addition of 4A molecular sieves could tremendously facilitated the formation of cyclohexylimine though removal of H2O, which would improve the conversion of cyclohexanone and the selectivity of cyclohexylamine. Beside, the addition of ammonia in the fixed-bed reactor also contributed to the formation of cyclohexylamine. Meanwhile, reaction conditions including reaction temperature, hydrogen pressure and charging rate of the premix, were investigated. Under optimum conditions, the conversion of cyclohexanone was 99.0% and the selectivity of CyNH2 reached 83.90%.