packed-bed microreactor for continuous-flow

Research Article

Packed-Bed Microreactor for Continuous-FlowAdipic Acid Synthesis from Cyclohexene andHydrogen Peroxide

The synthesis of adipic acid by means of a direct oxidation of cyclohexene by hy-drogen peroxide was carried out in a continuous-flow packed-bed microreactor.The reaction uses Na2WO4·2H2O as a catalyst and [CH3(n-C8H17)3N]HSO4 as aphase transfer catalyst without additional solvent. A parametric process optimiza-tion, such as glass beads size, residence time, concentration of hydrogen peroxide,addition of acid, reaction temperature, and molar ratios of reactants and cata-lysts, was performed. It is demonstrated that smaller glass beads result in a betteryield of adipic acid and that the addition of acid plays an important role in theoxidation of cyclohexene to adipic acid. Based on the concept of Novel ProcessWindows, the influence of elevated temperatures is investigated.

Keywords: Adipic acid, Hydrogen peroxide, Micro process technology, Novel ProcessWindows, Packed-bed microreactor

Received: December 13, 2012; revised: January 22, 2013; accepted: February 01, 2013

DOI: 10.1002/ceat.201200703

1 Introduction

Adipic acid is an important intermediate for the production ofnylon-6,6 and other products [1]. Nylon-6,6 polyamide ismainly used for the manufacturing of high-performance mate-rials, such as carpet fibers, ropes, and tire reinforcements, andthe annual world production of adipic acid is about 3.5 milliontons. Most commercial processes to produce adipic acid in-clude a two-step oxidation of cyclohexane [2]. It involves anaerobic oxidation of cyclohexane to obtain a mixture of cyclo-hexanone and cyclohexanol, i.e., K/A oil, followed by a nitricacid oxidation of K/A oil to obtain adipic acid. Although thisprocess is cost-effective, a large amount of nitrous oxide(N2O) is produced as a consequence of the used nitric acid asthe oxidant. N2O is a major greenhouse gas and air pollutantand its global warming potential exceeds the one from carbondioxide with a factor of 298 [3]. So, a more environmentallybenign procedure for synthesizing adipic acid is highly desired.

Nowadays, oxidation processes which employ green oxi-dants, such as oxygen or hydrogen peroxide, are attracting sig-nificant interest from the industrial community. In order toactivate the C–H bond with molecular oxygen, harsh reactionconditions, such as high temperature and pressure, are typical-

ly needed [4–6]. In addition, aerobic oxidation processes areoften difficult to control and problems arise due to side reac-tions, e.g., overoxidation. Hydrogen peroxide has a high activeoxygen content (47 % active oxygen) and produces water asthe sole byproduct [7]. Therefore, an increasing number of re-searchers have started to use hydrogen peroxide for a widevariety of oxidation processes, such as the one-step oxidativecleavage of cyclohexene to synthesize adipic acid. One of thefirst reports was provided by Noyori and co-workers [8]. Anexcellent yield of adipic acid was obtained by using 30 % H2O2

to oxidize cyclohexene with Na2WO4·2H2O as catalyst and[CH3(n-C8H17)3N]HSO4 as phase-transfer catalyst under or-ganic solvent-free conditions (Fig. 1). Inspired by this land-mark paper, several other catalysts have been developed withvarying success to enable efficient adipic acid synthesis startingfrom cyclohexene [9–14]. To the best of our knowledge, all re-ports concerning adipic acid synthesis via a direct oxidation ofcyclohexene by hydrogen peroxide were carried out in a labo-ratory batch reactor, which required long reaction times (typi-cally exceeding 8 h total reaction time). These procedures havelimited scale-up potential due to the explosion hazards of hy-drogen peroxide encountered at large scale.

We surmised that the direct synthesis of adipic acid in a con-tinuous-flow microreactor would be advantageous. It has to benoted that the terminology direct synthesis is only correct in astrict sense on a laboratory scale. On an industrial level, cyclo-hexane has to be produced from benzene and thus constitutesone additional step. Compared to traditional batch reactors,continuous-flow microreactors supply several advantages, such

Chem. Eng. Technol. 2013, 36, No. 6, 1001–1009 © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.cet-journal.com

Minjing Shang

Timothy Noël

Qi Wang

Volker Hessel

Eindhoven University ofTechnology, Department ofChemical Engineeringand Chemistry,Micro Flow Chemistry &Process Technology,Eindhoven, The Netherlands.

–Correspondence: Prof. V. Hessel ([email protected]), Eindhoven Uni-versity of Technology, Department of Chemical Engineering andChemistry, Micro Flow Chemistry & Process Technology, DenDolech 2, 5600 MB Eindhoven, The Netherlands.

Adipic acid 1001

as high heat and mass transfer efficiency, the ease of scale-up,and the facile transition from laboratory to production scale[15–17]. In addition, in order to boost the reaction, the bene-fits of the Novel Process Windows concept will be exploited.Novel Process Windows offers the advantage of speeding upthe intrinsic kinetics by using high temperature and/or pres-sure, and/or reactant concentration, which means that the re-action can be completed within much shorter residence time[18–21].

An additional complication of the one-step oxidative cleav-age of cyclohexene concerns the use of biphasic reaction condi-tions. In batch, mechanically stirred reactors equipped withbaffles are commonly used. However, such reactors typicallygive rise to poorly defined interfacial areas and the yield isstrongly dependent on the stirring efficiency. Moreover, onlylimited surface-to-volume ratios of ca. 1000 m2m–3 are feasiblein stirred reactors [22]. Due to their high surface-to-volumeratios, microreactor technology has been utilized to facilitatesuch biphasic reactions. Consequently, excellent and reproduc-ible interfacial areas can be obtained. The use of segmentedflow leads to interfacial areas above 10 000 m2m–3 [23, 24]. Animprovement can be obtained by using dispersed or bubblyflow. Bubbly flow can be efficiently generated with micromix-ers and maintained in so-called orifice microreactors [25–27].This flow regime allows for an increase of the interfacial areato values above 150 000 m2m–3. Beside this, packed-bed micro-reactors can further improve the mass transfer between twoimmiscible liquid phases efficiently [28–33]. This operationallysimple design allows for the formation of stable dispersionsproviding droplets of small size, e.g., < 10 lm [34].

The results concerning the development of a microreactorapproach towards the synthesis of adipic acid starting from cy-

clohexene and hydrogen peroxide are reported. A packed-bedmicroreactor was used to intensify the interfacial contact be-tween the organic and the aqueous layer. High-temperatureprocessing was used to reduce the reaction times. Excellentspace time yields were obtained and provide a twenty-fold in-crease compared to laboratory batch conditions.

2 Experimental

2.1 Materials

Cyclohexene, hydrogen peroxide solution (30 and 50 wt %),sodium tungstate dihydrate, sulfuric acid, aliquat 336, sodiumbisulfate monohydrate, and butyl acetate were all purchasedfrom Sigma-Aldrich and used directly in the experiments with-out further purification. The phase transfer catalyst (PTC)[CH3(C8H12)3N]HSO4 was synthesized according to the ex-perimental procedures described in [35].

2.2 Experimental Setup and Procedures

Adipic acid synthesis was conducted using a packed-bed mi-croreactor setup depicted in Fig. 2. This microreactor consistsof a glass tube of 20 cm length and 10 mm internal diameter,which was filled with inert glass beads with a particle size dis-tribution of 212–300 lm (Fig. 3). The biphasic reactantstreams were introduced into the system with syringe pumps.The aqueous phase, which contains sodium tungstate and hy-drogen peroxide solution, was combined with the organicphase, which includes cyclohexene and phase transfer catalyst,

www.cet-journal.com © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Chem. Eng. Technol. 2013, 36, No. 6, 1001–1009

- no organic solvents

- no N2O generation

- high yielding

- H2O as sole byproduct

Na2WO4

[CH3(C8H17)3N]HSO4

+ 4 H2O2 HOOCCOOH

adipic acid

Advantages

Figure 1. One-step oxidative cleavage of cyclohexene to synthesize adipic acid.

Syringe pump

Syringe pump

Packed bed reactor

Micromixer

D

DHydrogen peroxide and sodium tungstate

Cyclohexene and phase transfer

catalyst

Product

Figure 2. Schematic representation of the microreactor setup for the synthesis of adipic acid from cyclohexene and H2O2 device.

1002 V. Hessel et al.

in a micromixer. Next, the biphasic mixture is introduced intoa packed-bed microreactor. After exiting the reactor, the sam-ples were collected into vials. The reaction temperature waskept constant by the circulating oil. The product samples werekept in ice overnight. The resulting white precipitate was sepa-rated by filtration and washed with butyl acetate. Then, theproduct was redissolved in the acetone and the solvent was re-moved in vacuo. Finally, adipic acid was obtained in pure formafter being dried overnight at 70 °C in a vacuum oven.

2.3 Measurement of Hydrogen PeroxideConcentration

The study on hydrogen peroxide degradation was carried outin the same packed-bed microreactor as the reaction. Typically,H2O2 with or without sulfuric acid and sodium tungstate waspumped into the reactor, which was kept at 100 °C. The con-centration of hydrogen peroxide was determined by iodo-metric titration. All the experiments were performed three-fold, i.e., values reported in this study constitute the average ofthree independent experiments.

2.4 Analyses

The samples were analyzed via melting point, 1H NMR,13C NMR, IR, and HPLC. Nuclear magnetic resonance spectrawere recorded on a Varian 400 MHz instrument. All 1H NMRare reported in d units, parts per million (ppm), and weremeasured relative to the signal for tetramethylsilane (0 ppm)in the deuterated solvent, unless otherwise stated. All 13C NMRare reported in ppm relative to tetramethylsilane (0 ppm), un-less otherwise stated, and all were obtained with 1H decou-pling. All IR spectra were taken on a Perkin-Elmer SpectrumOne equipped with a Universal ATR sampling accessory.

The residence time is calculated according to the equation:

t � Vvoid

v(1)

where Vvoid is the void volume of the packed-bed microreactorand v is the total flow rate of organic phase and aqueousphase.

The isolated yield is calculated via the following equation:

Y � WADA�MADA

ncy× 100 % (2)

where Y is the isolated yield of adipic acid, WADA is the mass ofthe product adipic acid, MADA is the molecular weight of adi-pic acid, and ncy is the molar number of cyclohexene.

The equation of space time yield (STY) is defined as:

STY � WADA

Vt(3)

where V is the volume of reaction and t is the residence time.

2.5 Typical Procedure to Obtain Isolated Yields ofAdipic Acid

A stainless-steel syringe, filled with cyclohexene (0.061 mol,6.2 mL) and [CH3(C8H12)3N]HSO4 (3.65 mmol, 1.7 g), wasfitted to a syringe pump. A plastic syringe, filled with Na2-

WO4·2H2O (4 mmol, 1.32 g), hydrogen peroxide solution(50 wt %, 20 g), and concentrated sulfuric acid (96 %, 0.22 g),was fitted to a second syringe pump. The reagents were subse-quently introduced into the microfluidic system (see Fig. 2) atthe appropriate flow rates to give a residence time of 20 min.Before data collection, the system was allowed to reach steady-state conditions. Next, a sample was collected for 20 min toobtain theoretically 17 mmol of product. The sample was keptin an ice bath over night after which a white precipitate wasformed. The crystals were collected via filtration and washedwith butyl acetate. Then, the sample was recrystallized fromacetone to yield 1.24 g (8.5 mmol, 50 % yield) of adipic acid asa white crystalline product. The purity of adipic acid was as-sessed with HPLC, 1H NMR, 13C NMR and melting point. Thisshowed that the target compound was very pure and theamount of impurity was below 5 %. Melting point = 151–152 °C (lit.: 151–152 °C) [8]. 1H NMR (400 MHz, CD3OD) d:1.64 (m, 4H), 2.31 (m, 4H) ppm. 13C NMR (100 MHz,CD3OD) d: 175.9, 33.2, 24.1 ppm. IR (HATR, cm–1): 2949,2923, 1684, 1462, 1428, 1407, 1275, 1191, 921, 690.

3 Results and Discussion

3.1 Reaction Performance of the Packed-Bed Reactorfor Adipic Acid Synthesis

The investigations were started by using a 5-m PEEK capillarymicroreactor with a diameter of 500 lm. In such open capil-laries, the combination of two immiscible liquid phases resultsin the formation of segmented (slug or Taylor) flow in whichtoroidal vortices are established that lead to enhanced mixing


Figure 3. Picture of the packed-bed microreactor. The microreac-tor consists of two concentric tubes. The outer part is used forheat exchange, and oil continuously circulates through it. The in-ner part consists of the packed bed and the tube is filled withglass beads (212–300 lm).

Adipic acid 1003

as compared to single-phase flows. During the course of theinvestigations, it was observed that hydrogen peroxide una-voidably tends to decompose to produce oxygen and water(Fig. 4). Consequently, a liquid/liquid/gas three-phase systemwas formed and influenced the interfacial area between hydro-gen peroxide and cyclohexene significantly. However, andmore importantly, it also had a very pronounced effect on theresidence time. The gas formation resulted in irreproducibleresidence times and, in addition, the reaction time was reducedsignificantly. Hence, only very low yields of adipic acid (< 5 %yield) were obtained in a capillary reactor under atmosphericpressure.

It was anticipated that inadequate mixing in segmented flowobtained in the capillary reactor was one of the main causesfor the observed low yields of adipic acid. It is known that in abubbly or dispersed flow regime much higher interfacial areascan be reached. Depending on the droplet size of the dispersedphase, surface-to-volume ratios above 150 000 m2m–3 can bereached [25]. One phenomenon that has to be taken intoaccount in the microreactor design is the occurrence ofcoalescence of the dispersed droplets. While orifice micro-reactors have been successfully employed to deliver a stablebubbly flow regime, they require high flow rates to obtainsmall droplets and prevent coalescence. The use of prolongedreaction times and thus low flow rates, in the direct oxidationof cyclohexene might, therefore, be problematic. In contrast, apacked-bed microreactor might be advantageous for our pur-poses [28–33]. The interstices among the packing material canbe seen as simulated microchannels and the comparably largecross-sectional area could efficiently avoid the influence of thein situ produced gas bubble on the main reaction flow. More-over, the packing material causes a continuous redispersion ofthe biphasic mixture and thus ensures a better mixing andlarger interfacial area between the two immiscible phases. Thisshould obviously improve the mass transfer performance.

A micromixer was used before the packed-bed microreactor,which predisperses the two phase immiscible reactant streams.Two types of micromixers were explored, one is the jet-decayinterdigital micromixer from the Institut für MikrotechnikMainz GmbH, the other one is the shear-induced T-micro-mixer. The reaction was conducted at 90 °C and near atmo-spheric pressure. The theoretical residence time was 20 min ne-glecting the influence of gas formation. Hydrogen peroxidewas added in a 10 % molar excess over the stoichiometricamount. It can be seen from Tab. 1 that, although the jet-decayinterdigital micromixer has a better mixing efficiency, the typeof micromixer did not have a major effect on the reaction out-come.

The glass beads, which are used as reactor packing, redis-perse the reactants in a continuous fashion. Consequently, itwas expected that the size of the glass beads is of great impor-tance for the reaction efficiency. Different sizes of glass beads

were explored and the results are summarized in Tab. 2. It canbe seen that in these experiments the effect is rather negligiblefor longer residence times. However, when the residence timeis reduced to 8 min, no product formation was observed forthe reactor packed with 1000-lm glass beads. Therefore, 212–300-lm glass beads were used for all the experiments reportedin this study (Fig. 5).


2 x H2O2 2 x H2O + O2

∆T

Figure 4. Decomposition of hydrogen peroxide at elevated tem-peratures.

Table 1. Effect of micromixers on the isolated yield of adipic acid.

Entry Mixer type Residencetime[min]

Isolated yieldadipic acid[%]

1 Jet-decay interdigital micromixer 8 5.2

2 Jet-decay interdigital micromixer 20 9.8

3 Shear-induced T-micromixer 8 4.5

4 Shear-induced T-micromixer 20 11.4

Reaction conditions: n(H2O2):n(cyclohexene):n(Na2WO4):n(PTC)= 440:100:10:10 (n denotes the molar ratio). For the jet-decay in-terdigital micromixer, standard mixing channels are approx.45 lm × 200 lm. For the shear-induced T-micromixer, the inter-nal diameter of the mixing channels is 500 lm. The internal di-ameter of the tube leading from the micromixer to the packedbed is 500 lm and the length is 20 cm.

(a) (b)

Figure 5. Glass beads used as packing material for the packed-bed microreactor: (a) 212–300 lm, (b) 1000 lm.

Table 2. Effect of glass beads size on the isolated yield of adipicacid.

Entry Size of glassbeads [lm] a

Residencetime [min]

Isolated yieldadipic acid [%]

1 212–300 8 4.5

2 212–300 20 11.4

3 1000 8 < 3

4 1000 20 10.6

Reaction conditions: The temperature of oil bath was 90 °C, thereaction pressure was near atmospheric pressure, and theo-retical residence time was 20 min. n(H2O2):n(cyclohexene):n(Na2WO4):n(PTC) = 440:100:10:10 (n denotes the molar ratio).a The void fraction of the packed bed with particle size 212–300 lm is estimated to be 39 % and 43 % for the packed bedwith 1 mm particles.


3.2 Reaction Condition Dependence

3.2.1 Concentration of H2O2

A first parameter that was investigated is the influence of theconcentration of hydrogen peroxide on the reaction outcome.From Fig. 6, it is immediately clear that a higher concentratedhydrogen peroxide solution leads to a better yield of adipic acid.

3.2.2 Acid

The use of acidic promoters is crucial for the direct oxidationof cyclohexene to adipic acid [36–39]. Addition of acid en-hances the stability and the oxidative properties of hydrogenperoxide. As indicated above, this stabilizing effect would beadvantageous since decomposition of hydrogen peroxide re-sults in the formation of water and oxygen gas and, thus, irre-producible residence times in the reactor. Moreover, the acidfunctions as a catalyst for the two hydrolysis steps in the reac-tion mechanism (Fig. 7).

The effect of acidity on the flow process was investigated.Hereto, sulfuric acid was added to the aqueous hydrogen per-oxide solution. The results are illustrated in Fig. 8. An increasein yield can be obtained until the acid concentration reaches0.22 M. Further increasing the acid concentration leads to de-crease in productivity.

The higher activity of the catalyst in acidic media can alsobe explained by protonation of the peroxytungstic acids, i.e.,H2WO5 and H2WO8 [40]. At first, the catalyst Na2WO4 is oxi-dized by hydrogen peroxide to peroxytungstic species. Increas-ing the acidity results in a protonated species which constitutesthe more active oxidation catalyst.

3.2.3 Temperature

Most syntheses of adipic acid from cyclohexene and hydrogenperoxide were carried out at reaction temperatures below100 °C. Due to thermal runaways and the use of explosive ha-zardous hydrogen peroxide, it is not safe to use elevated reac-tion temperatures under batch conditions. However, the use ofmicroflow conditions can facilitate these rather harsh reactionconditions [41]. As can be concluded from Fig. 9, the reactiontemperature exerts a great influence on the oxidation process.Optimal reaction conditions are obtained at a temperature of100 °C; notably, 50 % isolated yield could be obtained withinonly 20 min reaction time. Higher reaction temperatures weredetrimental for the reaction since pronounced decompositionof hydrogen peroxide was visible.


02468

1012141618

30% 50%Concentration of hydrogen peroxide

Yie

ld o

f adi

pic

acid

(%)

Figure 6. Comparison of the isolated yields of adipic acid basedon the different concentration of H2O2. Reaction conditions: Thetemperature of oil bath was kept at 90 °C, the reaction pressurewas near atmospheric pressure, and the theoretical residencetime was 20 min. n(H2O2):n(cyclohexene):n(Na2WO4):n(PTC) =440:100:6:6 (n denotes the molar ratio).

HOOCCOOH

adipic acid

oxidationO

hydrolysis

H2O

OH

OH

oxidation OH

O

oxidationO

O

OH

oxidationO

O

O

hydrolysis

H2O

Figure 7. Proposed reaction pathway for the oxidation of cyclohexene by H2O2 to produce adipic acid [8].

0

5

10

15

20

25

30

35

40

0 0,1 0,2 0,3 0,4

Concentra�on of sulfuric acid (M)

Yiel

dof

adi

pic

acid

(%)

Figure 8. Effect of H2SO4 concentration on the isolated yield ofadipic acid. Reaction conditions: The temperature of oil bathwas 90 °C, the reaction pressure was near atmospheric pressure,and theoretical residence time was 20 min. n(H2O2):n(cyclohexe-ne):n(Na2WO4):n(PTC) = 440:100:6:6 (n denotes the molar ratio).

Adipic acid 1005

3.2.4 Residence Time

In the reported batch procedures, the direct oxidation of cyclo-hexene to adipic acid requires several hours to obtain full con-version [9–14]. In flow, the reaction could be accelerated sig-nificantly by utilizing harsh reaction conditions, i.e., a reactiontemperature of 100 °C and the use of a highly concentrated hy-drogen peroxide solution (50 %) resulted in the formation ofadipic acid (50 wt % isolated yield) within 20 min. FromFig. 10, it can be found that the isolated yield of adipic acidrises when the residence time increases. It is well known thatthe flow rate has an obvious influence on the hydrodynamicsand mass transfer of immiscible liquid-liquid two phases.Shorter residence times, and thus higher flow rates, result in ahigher mixing efficiency of immiscible biphasic mixtures [34].However, the yield of adipic acid in the packed-bed microreac-

tor is not only dependent on the mass transfer performancebut also on the total reaction time. The positive effect of theincrease of residence time resulted in an optimal residencetime of 20 min (Fig. 10) [32].

3.2.5 Catalysts

Next, the influence of the catalyst and phase transfer catalystwas investigated. In Fig. 11, it was found that the optimalamount of catalyst and phase transfer catalyst is 6 mol %. Add-ing more catalyst does not lead to a further increase in reactionyield. Varying the ratio of oxidation catalyst to phase transfercatalyst does not lead to an improvement in productivity(Figs. 12, 13).


0

10

20

30

40

50

60

60 70 80 90 100 110 120Temperature (°C)

Yie

ld o

f adi

pic

acid

(%)

Figure 9. Effect of temperature on the isolated yield of adipicacid. Reaction conditions: The reaction pressure was near atmo-spheric pressure, theoretical residence time was 20 min and theconcentration of sulfuric acid was 0.22 M. n(H2O2):n(cyclo-hexene):n(Na2WO4):n(PTC) = 440:100:6:6 (n denotes the molarratio).

0

10

20

30

40

50

60

0 5 10 15 20 25

Isol

ated

yie

ld o

fadi

pic

acid

(%)

Residence time (min)

Figure 10. Effect of residence time on the isolated yield of adipicacid. Reaction conditions: The temperature of oil bath was100 °C, the reaction pressure was near atmospheric pressure, andthe concentration of sulfuric acid was 0.22 M. n(H2O2):n(cyclohex-ene):n(Na2WO4):n(PTC) = 440:100:6:6 (n denotes the molar ra-tio).

0

10

20

30

40

50

60

100:01:01 100:03:03 100:06:06 100:09:09

Yie

ld o

f adi

pic

acid

(%)

n(cyclohexene): n(Na2WO4): n(PTC)

Figure 11. Effect of different molar ratios of reactant and cata-lysts. Reaction conditions: The temperature of oil bath was100 °C, the reaction pressure was near atmospheric pressure,the theoretical residence time was 20 min, and the concentrationof sulfuric acid was 0.22 M. n(H2O2):n(cyclohexene) = 440:100(n denotes the molar ratio).

0

10

20

30

40

50

60

100:01:06 100:03:06 100:06:06 100:09:06

n(cyclohexene): n(PTC):n(Na2WO4)

Yie

ld o

f adi

pic

acid

(%)

Figure 12. Effect of different molar ratios of reactant and cata-lysts. Reaction conditions: The temperature of oil bath was100 °C, the reaction pressure was near atmospheric pressure,the theoretical residence time was 20 min and the concentrationof sulfuric acid was 0.22 M. n(H2O2):n(cyclohexene) = 440:100(n denotes the molar ratio).


3.2.6 Decomposition of Hydrogen Peroxide

It is known that hydrogen peroxide decomposes at elevatedtemperatures to produce water and oxygen. Here, the influenceof the studied reaction conditions on the decomposition of hy-drogen peroxide (see Tab. 3) was investigated. It is found thathigh reaction temperatures do not lead to a significant en-hancement of the decomposition of hydrogen peroxide withinthe residence times used in this study (Tab. 3, entry 2). Addi-tion of catalyst and sulfuric acid results in limited decomposi-tion of hydrogen peroxide (Tab. 3, entry 3). Although a slightexcess of hydrogen peroxide is used, it is almost completelyconsumed under typical reaction conditions (Tab. 3, Entry 4).This suggests that more hydrogen peroxide is required to ob-tain full conversion of cyclohexene under continuous-flow re-action conditions.

Fig. 14 illustrates the effect of excess hydrogen peroxide onthe isolated yield of adipic acid. Obviously, the influence of ex-cess of hydrogen peroxide on the yield of adipic acid is not sub-stantial. At the moment, the reason for this finding is not entirelyclear and further investigations are currently in progress.

3.3 Microreactor Clogging

Microreactor clogging constitutes one of the major challengesfor micro process technology [42, 43]. Recently, several solu-tions for this problem have been developed [42–45]. Duringthe course of the current investigations, never microreactorblockage inside the packed-bed microreactor was observed. Atthe elevated temperatures used to boost the reaction, the solu-bility of adipic acid was sufficiently high to remain in solution.However, upon exiting the heated microreactor zone, deposi-tion of adipic acid was observed in the tubing which led toconstriction of the microchannel and, eventually, to blockageof the whole microreactor setup [46]. This phenomenon couldbe efficiently avoided by minimizing the length of the capillarytubing after the heated zone.

3.4 Comparison for Batch Reaction and Flow Reaction

In Tab. 4, a comparison between the space time yields (STY)for the batch reaction [8] and the one obtained in the presentstudy under continuous-flow conditions is presented. It is im-


Table 3. Analysis of the decomposition of hydrogen peroxide.

Entry Reaction conditions H2O2

concentration[wt %]

1 Initial H2O2 concentration 49

2 H2O2 + 100 °C a 47

3 H2O2 + 100 °C + Na2WO4 + H2SO4b 42

4 Typical reaction conditions c 2

Reaction conditions: a The theoretical residence time was20 min. b The theoretical residence time was 20 min, and theconcentration of sulfuric acid is 0.22 M. n(H2O2):n(Na2WO4) =440:6 (n denotes the molar ratio). c The temperature of oil bathwas 100 °C, the reaction pressure was near atmospheric pres-sure, the theoretical residence time was 20 min, and the concen-tration of sulfuric acid was 0.22 M. n(H2O2):n(cyclohexene):n(Na2WO4):n(PTC) = 440:100:6:6.

0

10

20

30

40

50

60

100:06:01 100:06:03 100:06:06 100:06:09

n(cyclohexene): n(PTC):n(Na2WO4)

Yie

ld o

f adi

pic

acid

(%)

Figure 13. Effect of different molar ratios of reactant and cata-lysts. Reaction conditions: The temperature of oil bath was100 °C, the reaction pressure was near atmospheric pressure,the theoretical residence time was 20 min and the concentrationof sulfuric acid was 0.22 M. n(H2O2):n(cyclohexene)= 440:100(n denotes the molar ratio).

30

35

40

45

50

55

0 20 40 60 80Excess of hydrogen peroxide (%)

Yie

ld o

f adi

pic

acid

(%)

Figure 14. Effect of the excess of hydrogen peroxide. Reactionconditions: The temperature of oil bath was 100 °C, and reactionpressure was near atmospheric pressure, the theoretical resi-dence time was 20 min and the concentration of sulfuric acidwas 0.22 M. n(cyclohexene):n(Na2WO4):n(PTC) = 100:6:6 (n de-notes the molar ratio).

Table 4. Comparison between batch reaction and flow reactionon the isolated yield of adipic acid.

Entry Reactor Residencetime [min]

STY[kg L–1h–1]

1 Batch reactor [8] 480 0.03

2 Packed-bed microreactor 20 0.57

Adipic acid 1007

mediately clear that the direct oxidation reaction of cyclohex-ene to adipic acid in a packed-bed microreactor greatly im-proves the space time yield.

4 Conclusions

A new microflow process has been described for the synthesisof adipic acid starting from cyclohexene and hydrogen perox-ide in a packed-bed microreactor. It is demonstrated that theisolated yield of adipic acid can reach 50 % within 20 min un-der intensified reaction conditions. Optimal reaction condi-tions involve the addition of sulfuric acid to stabilize hydrogenperoxide, accelerate the hydrolysis steps, and to form a moreactive oxidation catalyst. High reaction temperatures were fea-sible in this setup and 100 °C proved to be optimal. Further-more, the nature of the decomposition of hydrogen peroxideunder these reaction conditions was evaluated. The space timeyield obtained in the microreactor setup was calculated and atwenty-fold increase was found when compared to the batchreaction. It is believed that this direct oxidation process has agreat potential in microreactors. Further research in our labs isdevoted to reach full conversion in the microreactor setup andto limit the formation of gas to control the residence timemore precisely.

Acknowledgment

Funding by the Advanced European Research Council Grant“Novel Process Windows – Boosted Micro Process Techno-logy” under grant agreement No. 267443 is kindly acknowl-edged. M. S. thanks the European Research Council and Chi-nese Scholarship Council for financial support. T. N. wouldlike to acknowledge support from the Netherlands Organiza-tion for Scientific Research (NWO) for a VENI grant.

The authors have declared no conflict of interest.

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