Article pubs.acs.org/OPRD
Organocatalyzed Beckmann Rearrangement of Cyclohexanone Oxime in a Microchemical System Jisong Zhang,* Chen Dong, Chencan Du, and Guangsheng Luo* The State Key Laboratory of Chemical Engineering, Department of Chemical Engineering, Tsinghua University, Beijing 100084, China S Supporting Information *
ABSTRACT: A microchemical system, constructed with two micromixers and a delay loop, is designed to carry out the organocatalyzed Beckmann rearrangement of cyclohexanone oxime to ε-caprolactam with trifluoroacetic acid as the catalyst. In the microsystem, cyclohexanone oxime which is dissolved in acetonitrile mixes with trifluoroacetic acid in the first micromixer to realize uniform reaction condition, and then the mixture passes through the delay loop to continue the reaction. Finally, a large amount of acetonitrile is pumped into the second micromixer to stop the reaction by cooling and diluting the reaction system. The viscosity and reaction enthalpy of the organic reaction system are determined. The results show that both two are favorable for avoiding the clogging, increasing the heat transfer and improving the process safety. Two different catalytic systems are adopted and elevated in this microsystem. The influences of temperature, residence time, and oxime concentration on the reaction performance are investigated. Under optimized conditions, the reaction can be accomplished with a residence time less than 48 s and the selectivity of 99+%. The results show that Beckmann rearrangement can be realized in the microsystem with much more efficiency and safety.
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INTRODUCTION
ε-Caprolactam (CPL), the monomer for nylon-6, is mainly produced by the classical Beckmann rearrangement of cyclohexanone oxime (COX), which usually employs oleum as the catalyst.1,2 This conventional process suffers from several serious problems, such as the high byproduction of ammonium sulfate. Nearly 2 tons of ammonium sulfate per ton of product can be produced in the rearrangement process.3,4 Process safety is also a serious issue as oleum is strongly hazardous and corrosive. Since the rearrangement reaction is very rapid and highly exothermic, an external circulation technology has to be applied to control the reaction temperature, and the recycle loop can be as high as >50 relative to the cyclohexanone oxime feed, which results in a quite large reactor volume and a long residence time. The long residence time normally ranging from 15 to 180 min, has a negative effect on the selectivity to caprolactam.5 Recently, much progress has been made on the Beckmann rearrangement with organics as the catalysts.6−11 Luca et al.12 reported that a variety of ketoximes can be easily converted into corresponding amides catalyzed by 2,4,6-trichlorotriazine (cyanuric chloride, TCT) in N,N-dimethylformamide (DMF). A similar catalytic system has also been developed by using TCT in the presence of HCl or ZnCl2, which could greatly increase the reaction rate.13 More recently, trifluoroacetic acid (TFA) was used as the catalyst for the Beckmann rearrangement (Figure 1), and an excellent yield was obtained.14,15 TFA, as the organic acid, has a weak interaction with caprolactam, which could be separated by distillation or solvent extraction.16 As a result, the use of TFA could avoid the production of ammonium sulfate in the rearrangement step. However, compared with the industrial process, the process still carries © XXXX American Chemical Society
Figure 1. Beckmann rearrangement of COX to CPL with trifluoroacetic acid as the catalyst.
several drawbacks, such as the low selectivity (83−95%) and slow reaction rate (1.2 × 10−5 mol/(L·s), 343 K). In our previous work, a modified catalytic system based on TFA has been proposed to carry out the Beckmann rearrangement of cyclohexanone oxime.17 High selectivity to caprolactam (>99%) has been successfully obtained, and the average reaction rate was increased to 2.1 × 10−4 mol/(L·s) at 343 K. However, the reaction rate is still rather slow compared with the conventional catalyst of oleum,18 and the reaction time required is as long as 40 min. The low boiling point (345.5 K) and the highly corrosive characteristic of TFA result in that the reaction is difficult to be carried out at higher temperature in batch reactors. Also, much TFA would exist in the gas phase and decrease the TFA concentration in the reaction mixture. The development of microreaction technology provides a promising method to intensify the rearrangement process in the organic catalyst.19−22 First of all, the microreaction technology can enhance mixing of the reactants and give a good control of the reaction conditions.23−25 Second, higher pressure is easily operated, and then the reaction can be proceeded at higher temperature and decrease the evaporation of TFA, which may greatly enhance the reaction rate.26,27 Finally, the small volume usage and easy use of anticorrosive materials in the microReceived: November 26, 2014
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DOI: 10.1021/op500370u Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Article
Organic Process Research & Development reaction system improve the process safety.28,29 As a result, the advantages of better control of reaction conditions and inherent safety nature make the microreactor adoption desirable. In this work, the viscosity and reaction enthalpy of the organic reaction system were first determined. A microchemical system was specially designed to carry out the organocatalyzed Beckmann rearrangement of COX. COX dissolved in acetonitrile would mix with TFA in the first micromixer. The rearrangement reaction proceeded in the delay loop connecting downstream directly to the micromixer. Then a large amount of acetonitrile was pumped into the second micromixer to stop the reaction. The influences of reaction temperature, reactant concentration, and residence time on the reaction performance were elevated. A performance comparison between the microreaction process and the batch process is presented.
rise for Beckmann rearrangement. This is another reason why the inert organic solvent is applied in the rearrangement with oleum as the catalyst in microreactors. It is for heat removal as it can dilute the reactants and lower temperature gradient. Here we try to study the reaction enthalpy of Beckmann rearrangement in the TFA system. The experiments were performed by Calvet calorimeter (C80, Setaram, France). Two catalytic systems were adopted. One is similar to the literature15 in which acetonitrile mass fraction in TFA is 85 wt %. The other is similar to our previous work in which acetonitrile mass fraction in TFA is 15 wt %. The temperature during the experiment was kept at 65 °C, and the COX mass fractions in both two catalytic systems were 3 wt %. The results are shown in Table 1. For the literature catalytic
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Table 1. Reaction enthalpy in the TFA catalytic system
RESULTS AND DISCUSSION Viscosity of the Reaction Mixture. In our previous work,14 we have reported that the viscosity of the reaction mixture in oleum can be as high as 1000 mPa·s even at 80 °C (caprolactam mass fraction: 50 wt %). The extremely high viscosity of the reaction mixture greatly increases clogging problems and decrease the mass and heat transfer in the reactor. This is also a reason why Beckmann rearrangement in the microreaction system has to be designed as heterogeneous. The oleum phase has to be dispersed by inert organic solvent dissolving COX. During the reaction, COX will transfer from the organic solvent to oleum forming the viscous mixture. The existence of organic solvent can separate the viscous mixture and reduce the clogging problem. Here we try to study the viscosity of the reaction mixture in TFA. Figure 2 shows the
acetonitrile mass fraction (wt %)
time (min)
conversion (%)
heat released (kJ/mol)
85 wt % 15 wt %
20 60
5 95
40 162
system, no heat is released after 20 min, and the total heat released is only 40 kJ/mol. The sample is then diluted and analyzed by gas chromatography. The conversion of COX is 5%, indicating that most heat come from dissolving of COX in TFA. For the modified catalytic system, no heat is released after 60 min, and the total heat released is 162 kJ/mol. The sample is also diluted and analyzed by gas chromatography. The conversion of COX is 95%, indicating that most heat come from Beckmann rearrangement of COX in TFA. According to the above data, we can calculate that the dissolution heat of COX in TFA is about 33 kJ/mol, and the reaction heat of Beckmann rearrangement in TFA is about 136 kJ/mol. The total reaction enthalpy of Beckmann rearrangement in TFA is 169 kJ/mol, 32% lower than that in oleum. As we know that COX and CPL are all protonated to form the corresponding hydrosulfate in the oleum phase.30 The results of reaction enthalpy here indicate that the interaction between COX, CPL, and TFA is much lower than that between COX, CPL, and oleum. In addition, the reduced reaction enthalpy can decrease the heat released during the rearrangement and improve the safety. Reaction Performance of the Literature Catalytic System. Figure 3 shows the reaction performance with the literature catalytic system in the microsystem. The acetonitrile content in the reaction mixture is about 82 wt %, and the molar concentration of COX is about 0.12 mol/L, similar to the literature system.30 As shown in Figure 3a, the reaction rate is greatly enhanced in the microreactor. The conversion of COX can be as high as 92% within 100 s at the temperature of 130 °C. Meanwhile, the reaction time in the batch reactor is as long as 100−1000 min. As for the average reaction rate, it is about 1.2 × 10−5 mol/(L·s) at 70 °C in the literature. The values in the microsystem are 2.9 × 10−4 mol/(L·s) (110 °C) and 1.1 × 10−3 mol/(L·s) (130 °C). The results indicate that the application of microreactor can greatly increase the throughput of the catalytic system. Furthermore, we can find that the temperature rise can greatly increase the reaction rate. The apparent activation energy is about 94 kJ/mol estimated from the initial reaction rates at different temperatures, which is the same with the value (94 kJ/mol) in the literature.
Figure 2. Viscosity of the TFA solution with different caprolactam mass fractions.
viscosity of TFA solution with different caprolactam mass fractions. The temperature ranges from 30 to 70 °C, and the caprolactam mass fraction ranges from 15 wt % to 49.6 wt %. The results indicate that the viscosity increases with the increase of caprolactam mass fraction and with the decrease of temperature. However, the viscosity is quite small, ranging from 2 to 20 mPa·s, about 2 orders of magnitude lower than that of the oleum system. So it can be accepted that organocatalyzed Beckmann rearrangement in the microreaction system is homogeneous. Furthermore, relatively low viscosity of the TFA catalytic system can avoid the clogging problem and increase the heat and mass transfer rate, making the process much safer. Reaction Enthalpy of Beckmann Rearrangement in the Organic Catalyst. It has been noted that the reaction enthalpy of Beckmann rearrangement in oleum is as high as 254 kJ/mol.4 It is always a challenging issue to control temperature B
DOI: 10.1021/op500370u Org. Process Res. Dev. XXXX, XXX, XXX−XXX
Article
Organic Process Research & Development
Figure 3. Reaction performance of the literature catalytic system. (a) Effect of temperature and residence time on the conversion of COX; (b) effect of temperature and residence time on the selectivity to CPL. The COX concentration in acetonitrile was 2 wt %. The flow rate of COX solution and TFA were controlled at 10 mL/min and 1 mL/min, respectively. The residence time ranged from 21 to 98 s. The temperature of the oil bath ranged from 110 to 130 °C.
As shown in Figure 3 (b), the selectivity increases with the increase of the residence time at different temperatures. In our experiments, we find that the concentration of side product (cyclohexanone) increases quickly when the conversion of COX is less than 20% and then it keeps nearly constant after the conversion of about 40% until the reaction is finished (See Supporting Information Figure S-2). The similar results are also described in the literature14,15 and our previous work.17 The reason has been given in our previous work.17 The hydrolysis of COX to cyclohexanone (CYC) is main side reaction and it is fast and reversible. During the rearrangement reaction, a few COX would quickly hydrolyze to CYC and hydroxylamine reaching an equilibrium state and then the CYC concentration keeps nearly constant. This is the reason why the selectivity to CPL will increase with the reaction going on. As a result, we can calculate the selectivity in the microsystem is about 93% ∼ 96% when the conversion of COX is 100%, higher than the value (83−95%) in the batch reactor. So it can be concluded that the application of microreactor can also improve the selectivity with the literature catalytic system. This is mainly due to the increase of temperature. According to the details studies of side reaction in the literature catalytic system,14 the activation energy of side reaction (61 kJ/mol) is lower than that of the rearrangement. This is the reason why higher temperature gives higher selectivity to CPL. The reaction performance of the modified catalytic system. In this section, we try to test the reaction performance of the modified catalytic system. In both Figures 4 and 5, the
Figure 5. Effect of temperature on the reaction performance in the modified catalytic system. The COX concentration in acetonitrile was 10 wt %. The flow rate of COX solution and TFA were controlled at 0.4 mL/min and 1.6 mL/min, respectively. The residence time was 48 s. The temperature of the oil bath ranged from 80 to 130 °C.
acetonitrile content in the reaction mixture is about 10 wt % and the molar concentration of COX is about 0.14 mol/L. Figure 4 shows the effect of residence time on the conversion of COX and selectivity to CPL at 100 °C. With the increase of residence time, the conversion increases from about 55% (13 s) to 100% (38 s). Compared with the conversion of 10% (48 s) at 110 °C in Figure 3 (a), it can be concluded that the modified catalytic system can greatly increase the reaction rate. As for the selectivity, it is about 90% when the residence time is only 13 s. Similar to the results shown in Figure 3 (b), the selectivity increases with the increase of the residence time. Due to the TFA high concentration, the unstable hydroxylamine will be combined by TFA. As a result, CYC and hydroxylamine will be transferred to COX when the conversion of COX is close to 100%. The trend of CYC is provided in Figure S-3 of Supporting Information. As shown in Figure 4, when the conversion is about 100% (38 s), the selectivity is increase to 99+%, which is the same as the results in batch at lower temperature.17 Figure 5 shows the effect of temperature on the conversion of COX and selectivity to CPL with a residence time of 48 s. It is found that temperature has a large effect on the reaction rate. The conversion is only about 15% at 80 °C, while it is 90% at 90 °C. When temperature is larger than 100 °C, a conversion of 100% can be achieved in the microsystem. The average reaction rate here is about 2.6 × 10−3 mol/(L·s) at 90 °C, while it is 2.1 × 10−4 mol/(L·s) at 70 °C in our previous work.17 For the selectivity, it is 99+% from 100 to 130 °C, indicating that the higher temperature (
