The effect of operating conditions on acylation of 2-methylnaphthalene in a microchannel reactor☆

Wenpeng Li,Suohe Yang,Xiaoyan Guo,Guangxiang He,Haibo Jin*

Beijing Key Laboratory of Fuels Cleaning and Advanced Catalytic Emission Reduction Technology,College of Chemical Engineering,Beijing Institute of Petrochemical Technology,Beijing 101617,China

Keywords:Acylation Microchannel reactor 2-Methylnaphthalene 2-Methyl-6-propionylnaphthalene

A B S T R A C T Acylation of 2-methylnaphthalene(2-MN)is a very important reaction in organic synthesis,and the effiency of the continuous reactor is more than one of the batch reactor.Considering that the Friedel–Crafts acylation is a rapid exothermic reaction,in this study,we perform the acylation of 2-MN in a stainless steel microchannel flow reactor,which is characterized by high mass and heat transfer rates.The effect of reactant ratio,mixing temperature,reaction temperature,and reaction time on product yield and selectivity were investigated.Under the optimal conditions,2-methyl-6-propionylnaphthalene(2,6-MPN)was obtained in 85.8%yield with 87.5%selectivity.Compared with the conventional batch system,the continuous flow microchannel reactor providesa more efficient method for the synthesis of 2,6-MPN.

1.Introduction

In recent time,microchannel reactors are being widely used for manufacturing various products such as fine chemicals,biochemical,and pharmaceuticals[1–4].Compared to conventional reaction devices,microchannel reactors have several advantages:(i)precise control of reactant ratio,(ii)fast and direct scale-up,(iii)high specific surface area and heat transfer rate,(iv)short residence time and little byproduct formation,and(v)safe operation and low pollution.The microreactor technology has been discussed in detail elsewhere,and different types of reactions have been investigated in continuous flow systems[5].Friedel–Crafts reactions were found to be particularly suitable for microchannel reactors.

Friedel–Crafts alkylation in microchannel reactor has been studied by several researchers[6,7].In particular,Freidel–Crafts acylation reaction plays an important role in organic synthesis.For instance,acylation is a key step in the continuous- flow microreactor synthesis of an aminonaphthalene derivative[8],resulting in 100%yield compared to the 86%–96%yield of the corresponding batch reaction.Moreover,a safe and efficient continuous- flow synthesis of 1,3,4-oxadiazoles via acylation of 5-substituted tetrazoles has been developed by Reichart and Kappe[9],who reported that the reaction in a Flow Syn microreactor(Uniqsis Ltd.)afforded the target product with yield and selectivity much higher than those obtained in batch processes.The synthesis of sugar 6-monoesters by acylation of sugars with vinyl carboxylates in a microchannel flow reactor has also been developed[10].In addition,Jamison studied the synthesis of o-isopropyl propionylbenzene by the acylation of isopropylbenzene with propionyl chloride(PC)in a per fluoroalkoxy reactor[11],using PC itself as the solvent to dissolve AlCl3.Under the optimal conditions of 40°C and 1.25 min,the desired o-isopropyl propionylbenzene was obtained in 99%yield.The acylation of 2-methylnaphthalene (2-MN) by PC gives 2-methyl-6-propionylnaphthalene(2,6-MPN),which is important raw materials for the production of 2,6-naphthalene dicarboxylic acids[12–14].Similarly,acylation of 2-MN by acetyl chloride(AC)gives 2-methyl-6-acetylnaphthalene(2,6-MAN).

Liquid-phase Friedel–Crafts acylation of 2-MN over a zeolite catalyst has been previously reported[15–17].In this reaction,the zeolite catalyst can be easily recovered,but it shows low catalytic activity.Friedel–Crafts acylation has also been performed in an ionic liquid[18,19],which shows good yield and good selectivity,but needs long reaction time.The acylation of 2-MN is commonly performed using metal chlorides and acid chlorides as catalysts and acylating agents,respectively,via the mechanism shown in Fig.1[20].Several studies reported the conventional batch acylation of 2-MN[21,22],which gives the target product with high selectivity but in low yield.Under these conditions,a longer reaction time and higher amounts of catalyst and acylating agent were required.Interestingly,the acylation of 2-MN in a microchannel reactor has not been reported so far.

Fig.1.Mechanism of the acylation reaction of 2-MN RCOCl:acetyl chloride(AC)or propionyl chloride(PC);Product:2,6-MAN or 2,6-MPN.

In this work,the 2-MN acylation in a continuous microchannel reactor was investigated,and the effect of the reaction conditions on the yield and selectivity of the target product are discussed.

2.Experimental

2.1.Materials

2-MN(98%),PC(98%),AC(98%),AlCl3(99%),Zn Cl2(99%),and FeCl3(99%)were purchased from Shanghai Macklin Biochemical Co.,Ltd.Nitrobenzene(98%),1,2-dichloroethane(98%),and dichlorobenzene(98%)were purchased from Tianjin Damao Chemical Reagent Factory.

2.2.Method

The experimental setup is shown in Fig.2 and the continuous- flow acylation reaction of 2-MN involves the following steps:

(i)Preparation of the acylating solution:Nitrobenzene(13 ml)and AlCl3(2.8 g)were added to a glass-jacketed reactor(50 ml,Shanghai Han Connaught Instrument Co.,Ltd.)with stirring and cooling in an ice bath,followed by dropwise addition of PC(1.7 ml).The reaction was continued for 10 min after the addition was complete.

(ii)Preparation of the reactant solution:Nitrobenzene(15 ml)and 2-MN(2 g)were added to another glass-jacketed reactor(20°C).The mixture was stirred until complete dissolution of 2-MN in nitrobenzene.

(iii)Mixing and Reaction:The two solutions were loaded into two glass syringes(20 ml,Bolivian Pigeons,China),which were attached to two syringe pumps at the rate of 0.04 ml·min?1,and mixed in a static T-micromixer with cooling in an ice bath.The mixed solution entered the microchannel reactor at a constant temperature.

(iv)Washing:After the reaction,the solution entered the 2nd static T-micromixer.Water(0.8 ml·min?1,driven by a plunger pump)was introduced into the mixer,and the two liquids entered the 2nd microchannel immersed in an ultrasonic tank(40 kHz,160 W).The purpose of thew ashing step was to remove the acidic components of the solution such as chloride and aluminum ions.Ultrasonic treatment provided effective mixing of the two-phase water-nitrobenzene system[23].

In Fig.2,the inner diameter of T-micromixer is 0.5 mm,and because both solutions consist of an organic phase,the T-mixer was very efficient[24].As for the 2nd static T-micromixer,its inner diameter is also 0.5 mm.Since water and production solution are immiscible,ultrasonic treatment is necessary.The smaller the inner diameter of the microchannel reactor,the higher the mass and heat transfer efficiency.How ever,the flow resistance of the pipe increases with the decreasing diameter.Moreover,for a low flow resistance,a 6-m long stainless steel pipe with an inner diameter of 1 mm was used as the microchannel reactor.During the washing process,the system released hydrogen chloride gas,which would influence the residence time of the washing solution.Thus,a 4-m long washing pipe with the inner diameter of 2.5 mm was used.

2.3.Analysis methods

After the washing procedure,the organic phase was separated from the aqueous phase,and a small sample was taken and analyzed with a Shimadzu GC-2014 gas chromatograph equipped with a flame ionization detector and an HP-5 capillary column(50 m×0.2 mm×0.33 μm film thickness),using nitrogen as the carrier gas.An internal standardization method was used following the procedure of Grob[25].

Fig.2.The experimental setup 1-glass syringe;2-T-micromixer;3-microchannel reactor;4-washing pipe;5-thermocouple;6-ultrasonic tank;7-plunger pump;8-thermostatic bath.

The selectivity of the product was calculated from the mass balance equation as follow s:

and the yield was calculated from the following mass balance equation:

w here X is the selectivity(%,by mass)of 2-MPN;W1is the mass of 2-MPN;W2is the mass of all acylation products;Y is the yield(%,by mass)of 2-MPN;W3is the actual mass of 2-MPN;and W4is the theoretical mass of 2-MPN.

3.Results and Discussion

The continuous acylation reaction in the microchannel reactor was investigated under different conditions.The standard experimental conditions of acylation of 2-MN are that the molar of 2-MN:PC or AC:AlCl3=1:1.3:1.5;the catalyst is AlCl3;the acylating agent is PC;the solvent is nitrobenzene;the mixing temperature is?1 °C;the reaction temperature is 40°C,and there sidence time is 60 min.When investigating different reaction conditions,the investigated condition is changed and the other conditions remain unchanged.

The batchwise acylation of 2-MN was also carried out in a traditional glass-jacketed reactor for comparison.The effects of the reactant ratio,mixing temperature,reaction temperature,and reaction time on the product yield and selectivity were investigated.The reactants(molar ratio of 2-MN:PC:AlCl3=1:1.4:1.7)were dissolved in nitrobenzene,and under the optimal conditions of?1 °C mixing temperature and 30°C reaction temperature for reaction time of 300 min,the product was obtained with yield of 84.1%and selectivity of 86.4%.

3.1.Effect of catalyst

Friedel–Craftsacylation requiresa polar catalyst such as a Lew is acid,protonic acid,or acidic oxide.Among these,Lewis acids are most commonly used.In this study,the effect of AlCl3,FeCl3,and Zn Cl2on the acylation reaction of 2-MN was investigated,and the results are shown in Table 1.It was found that the catalytic activity of acid halides followed the order of AlCl3＞FeCl3＞Zn Cl2.Because Al3+is more electrophilic than Fe3+and Zn2+,the electrophilicity of[C2H5CO]+[AlCl4]?is higher than that of[C2H5CO]+[FeCl4]?and[C2H5CO]+[Zn Cl3]?.Thus,AlCl3was found to be the optimal catalyst and was used in the subsequent experiments.

Table 1Effect of catalyst on product selectivity and yield

3.2.Effect of solvent

The reaction was carried out in three different solvents,namely,nitrobenzene,1,2-dichloroethane,and p-dichlorobenzene,under the same experimental conditions,and the results are shown in Table 2.1,2-Dichloroethane and p-dichlorobenzene have lower boiling pointsthan nitrobenzene,allowing for easy separation of the product from the solvent by distillation;however,low product selectivity and yield were obtained in these solvents.Moreover,AlCl3has higher solubility in nitrobenzene than in 1,2-dichloroethane and p-dichlorobenzene.Hence,nitrobenzene was chosen as the solvent.

Table 2Effect of solvent on product selectivity and yield

3.3.Effect of molar ratio of reactants

The reaction was carried out using different ratios of reactants,and the resultsare given in Table 3.The molar ratio of reactants had a significant effect on the product yield and selectivity,and the best result was obtained using a2-MN:AlCl3:PCmolar ratio of 1:1.3:1.5.At higher molar ratios,the desired product selectivity and yield were not significantly affected,where as at lower ratios,the conversion of 2-MN decreased,with a negative effect on selectivity and yield.

Table 3Effect of molar ratio of reactants on selectivity and yield of the production

3.4.Effect of mixing temperature

The effect of mixing temperature(i.e.,the temperature at which the two solutions were mixed in the static T-micromixer)on the acylation reaction of 2-MN was investigated,and the results are given in Table 4.The mixing temperature was found to significantly affect the outcome of the reaction.At temperatures＞0°,PC is highly reactive,and free PC can react with[C2H5CO]+[AlCl4]?to form[(C2H5CO)3CHCH3CO]+[AlCl4]?or other complexes[26].Upon mixing,the two solutions rapidly released a lot of heat,and some[C2H5CO]+[AlCl4]?was converted into other complexes,affecting the product selectivity and yield.

Table 4Effect of mixing temperature on product selectivity and yield

3.5.Effect of reaction temperature

Fig.3.Effect of reaction temperature on product selectivity and yield.

The effect of the reaction temperature on product selectivity was investigated.As can be seen from Fig.3,the selectivity of 2,6-MPN increased with increasing temperature from 10 to 40°C,and then decreased at 50°C.On the contrary,the selectivity of 2,6-MAN increased with increasing temperature from 10 to 35°C,and then decreased at 40°C.At low temperatures,the reactants showed low reactivity,affecting the conversion of 2-MN.The reactivity of reactants increased with increasing temperature;how ever,the probability of side reactions also increased,and higher amounts of other monoacylated methylnaphthalene isomers were formed.Thus,the yield of the target product decreased even if the conversion was high.The highest 2,6-MPN selectivity and yield of 87.5%and 85.8%w ere achieved at a temperature of 40°C,where as the highest 2,6-MAN selectivity and yield of 75.9%and 74.4%w ere obtained at 35°C.

3.6.Effect of reaction time

The effect of reaction time on the acylation reaction was investigated;the reaction time was controlled by the flow rate through the syringe pump,and the results are shown in Fig.4.The selectivity of 2,6-MPN and 2,6-MAN increased with time up to 60 min,because at the beginning of the reaction some unstable product isomers were gradually converted into stable six-coordinate compounds.After this time,the selectivity remained essentially unchanged.As expected,a short reaction time resulted in a relatively low conversion rate of 2-MN,indicating that the reaction time had a significant influence on the yield of the desired product.At 60 min,the highest selectivity and yield of 2,6-MPN(87.5%and 85.8%,respectively)and 2,6-MAN(75.9%and 74.4%,respectively)were obtained.

Fig.4.Effect of reaction time on product selectivity and yield.

4.Conclusions

The acylation reaction of 2-MN in a microchannel reactor proved to be an efficient method for the synthesis of 2,6-MPN.The reactants(molar ratio of 2-MN:PC:AlCl3=1:1.3:1.5)were dissolved in nitrobenzene,and under the optimal conditions of mixing temperature?1°C,reaction temperature 40°C,and reaction time 60 min,the desired product was obtained in 85.8%yield with 87.5%selectivity.Compared to the conventional batch reaction,the product selectivity and yield were improved,and a lower amount of catalyst and acylating agent and a shorter reaction time were required.

Under the same reaction conditions,2,6-MPN was obtained in higher yield and selectivity than 2,6-MAN.This could be attributed to the greater electron cloud density of six-coordinate 2-MN and greater steric hindrance of the AlCl3-PC complex compared to that of the AlCl3-AC complex,which facilitates the substitution reaction of six-coordinate species.