Kinetics study of the N-formylation of aniline with DMF catalyzed by temperature-controlled Br?nsted ionic liquids

Yipeng Zheng, Zhennan Cao, Zheng Zhou, Gaodong Yang,Zhibing Zhang

School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China

Keywords:N-formylation of aniline Ionic liquid Temperature-controlled system Kinetic

ABSTRACT A series of SO3-functional Br?nsted acidic ionic liquids (SBAILs) were prepared to catalyze the Nformylation of aniline with DMF.The reaction conditions such as ionic liquid type,reaction temperature,catalyst loading and molar ratio of reactants were investigated.To the best of our knowledge, kinetic model for the N-formylation of aniline with DMF using SBAIL was firstly built and simulated.The studies on the reaction order of the reaction were evaluated by initial concentration method, and the kinetic parameters such as reaction rate constant and activation energy were proposed and used to explain the catalytic activities of the SBAILs catalysts.Accordingly, the recycling experiments showed that the SBAIL [Bsmim][HSO4] can be easily recovered and reused with stable activity.Further, the temperature-controlled study emphasized that the ionic liquid was easy to be separated and environmentally friendly.

1.Introduction

Formamides is one of the most valuable intermediates in pharmacological syntheses and important building blocks in synthetic and industrial organic chemistry [1,2].Formylaniline is produced by theN-formylation reaction of aniline and is one common and important formamides, which can be used as the intermediate for the synthesis of some optical materials, spices, dyes and drugs[3].Therefore, it is significant to study the reaction of theNformylation of aniline.

Conventionally, formic acid is widely used as formylation reagent for theN-formylation reaction because of the high formylating ability[4,5].However,it is reversible of the reaction of amines with formic acid to give water, which requires numerous water-carring agent to maintain high conversion [6,7].Additionally,it will bring about complex operation and high industrial cost.In recent years, a number of research studies on replacing formic acid withN,N-dimethylformamide (DMF) have been reported [8–10], because the reaction of aniline with DMF can avoid removing water from the reaction system and DMF is commercially available, inexpensive, low toxic, and easily separated.However, due to the low formylating ability, the reaction of aniline with DMF requires efficient catalytic system.

TheN-formylation of amines is typically catalyzed by metalcontaining catalysts for their high activities.Recently, a number of metals or metal complexes were reported forN-formylation reactions, such as Au/MOF-808(Zr) [11], Al-2(NMe2)(6) [12], copper [13], Fe(III) [14], HfCl4/KSF-polyDMAP [15], carbon nanotubegold nanohybrid (Au-CNT) [16], and so on.In addition, some new catalysts forN-formylation reactions were also investigated, for example, Suchandraetal.used graphene oxide (GO) to formylate aniline under metal-free conditions with 75% conversion [17],and Rasheedetal.found the H2SO4-SiO2catalytic system was excellent due to its manipulation ease, low-cost, and benign character[18].These catalysts exhibited good activities,however,their application confronted with some drawbacks such as metal cocatalyst, contamination, expensive catalyst, formidable separation,solvent usage, and recovery procedure.Hence, it is necessary to develop a new environmentally friendly strategy for theNformylation of aniline.

In recent years, ionic liquids (ILs) as environmental friendly reaction media has been applied in many areas due to excellent thermal stability, low vapor pressure, tunable acidity, remarkable solubility, recoverability and convenience in product separation[19].Br?nsted acidic ionic liquids(BAILs)are one important subset of ILs that have been applied in many fields.For example, BAILs[CyN1,1PrSO3H][p-TSA] was developed as efficient catalyst the transesterifification of palm oil and methanol [20].Recently, Zhaoetal.successfully synthesized several kinds of SO3-functionial ionic liquids as the catalyst to prepare trioxane with good catalytic activities [21].In particular, SO3-functionial Br?nsted acidic ionic liquids (SBAILs) have been exploited successfully as catalysts for theN-formylation reaction of amines and have obtained effective results[22].However,as far as concerned,the basic research about kinetics for theN-formylation reaction of aniline catalyzed by SBAILs is still absent.

Therefore, various SBAILs were prepared to study theNformylation of aniline with DMF in this work.The effects of various reaction conditions such as type of catalysts,temperature,catalyst loading and molar ratio of reactants were systematically discussed through well designed comparative catalytic experiments.Meanwhile, the kinetics machanism for theN-formylation of aniline with DMF was first time studied and the kinetics parameters were obtained.In addition, the selected SBAIL [Bsmim][HSO4] was approved to form a temperature-controlled system with reactants,which could enhance the catalyst separation and recoverable ability.In general,the green process developed in this work provided a new idea to produce formylaniline efficiently and the study of kinetics machanism may be used to guide production.

2.Experimental

2.1.Materials and reagents

N-Methylimidazole(98%,Bide Pharmatech Ltd.,China),triethylamine(99%,Aladdin reagent(Shanghai)Co.,Ltd),pyridine(99.5%,Aladdin reagent(Shanghai)Co.,Ltd),1,4-butane sultone(97%,Bide Pharmatech Ltd., China), sulphuric acid (98%, Nanjing Nanshi Chemical Reagent Co., Ltd),p-toluene sulfonic acid (97%, Aladdin reagent (Shanghai) Co., Ltd), methanesulfonic acid (99.5%, Aladdin reagent (Shanghai) Co., Ltd), aniline (99.5%, Aladdin reagent(Shanghai) Co., Ltd),N,N-dimethylformamide (99.5%, Bide Pharmatech Ltd., China) were used.

2.2.Preparation and characterization of ionic liquids

Five kinds of SBAILs and one kind of BAIL (as shown in Fig.1)were prepared according to the previously reported papers[23,24].1H NMR and13C NMR spectrum (BRUKER Ascend 400 MHz)of these ionic liquids were recorded.The detailed preparation and characterization of ionic liquids can be found in the Supplementary Material.

2.3.Procedure for the N-formylation of aniline

TheN-formylation reaction of aniline with DMF was carried out in a 50 ml three-necked flask equipped with a condenser and a thermometer, where aniline, DMF and catalyst were added at a certain ratio.The mixture was stirred at the designed temperature,and meanwhile a small amount of samples were taken out regularly for GC analysis.

2.4.Analysis

The samples were analyzed using a gas chromatograph (Shimadzu, GC-2014C) equipped with a hydrogen flame ionization detector (FID) and a methyl polysiloxane capillary column(WondaCap-5).Nitrogen at the flow rate of 3 ml?min-1was used as carrier gas.The temperatures of the column and the detector were kept at 513.15 and 523.15 K, respectively.

whereMformandManare the amount of formanilide and aniline,respectively.

3.Results and Discussion

3.1.Effects of different ionic liquids catalysts

Catalyst screening experiments were undertaken catalyzed by 20%(molar ratio based on aniline)of BAILs at 423.15 K to compare their catalytic activity and the results are presented in Table 1.It can be seen that the activity of [Bsmim][HSO4] was higher than[BSEt3N][HSO4] and [Hspy][HSO4] (Entry 1, 2, 3), which indicated that different zwitterions of SBAILs would affect the activities of SBAILs.And SBAILs with different anions were also investigated(Entry 4,5,6)and the results suggested that[Bsmim][HSO4]exhibited higher activity than [Bsmim][CH3SO3] and [Bsmim][p-(CH3)(C6H4)SO3H].Therefore, the activities of SBAILs depended on the combination of their zwitterions and donor acids.

Fig.1. The structures of ILs: (1) [Bsmim][HSO4], (2) [BSEt3N][HSO4], (3) [Hspy][HSO4], (4) [Bsmim][CH3SO3], (5) [Bsmim][p-(CH3)(C6H4)SO3H], (6) [Bmim][HSO4].

Table 1N-formylation of aniline with DMF using different catalysts

For comparison, the control experiments were conducted with H2SO4and [Bmim][HSO4] as catalyst respectively.As shown in the results, the conversion of aniline catalyzed by SBAILs were much higher than by H2SO4.And according to previous literature[20,25], the acidity of H2SO4was stronger than that of SBAILs,which indicated that the acidities of catalysts used in theNformylation reaction of aniline were not the main contributors to catalytic activities.The use of [Bmim][HSO4] resulted in much lower conversion (about 30%) compared with [Bsmim][HSO4].It is obvious from the results that SBAILs having —SO3H functionalization in cation were more active than BAIL without —SO3H functionalization.

In conclusion,the SBAILs[Bsmim][HSO4]was chosen as the catalyst for further optimization of reaction conditions and kinetics studies.

3.2.Optimization of catalyst loading

The influence of different catalyst loading on the conversion of aniline was studied by setting the catalyst loading at 5%,10%,15%,20%and 25%(mol),respectively.The results in Fig.2 indicated that with the addition of catalyst loading, the reaction rate of theNformylation reaction increased obviously.For example,the conversion of aniline increased rapidly from 29.918% to 63.678% within 60 min with the catalyst loading ranking from 5%to 20%.It demonstrated that the increase of catalyst loading provided more catalytic active centers which contributed to the conversion of theN-formylation reaction of aniline.However, there was only a tiny change in the conversion of aniline when the dosage was raised from 20% to 25%.It can be explained that only a part of catalytic active centers were involved in the reaction because of the limited reactants.Therefore,further more increase of catalyst loading was not necessary and 20% catalyst loading was suggested to be suitable and used in the rest optimization experiments.

Fig.2. Effects of catalyst loading (SBAIL type: [Bsmim][HSO4]; temperature:423.15 K; initial molar ratio of aniline and DMF was 1:6).

3.3.Optimization of initial molar ratio of reactants

TheN-formylation reaction of aniline with DMF is a irreversible reaction,so reactant ratio affects the conversion of aniline through changing the reaction rate.Because aniline was taken as the limiting reactant in this work, the effects on the molar ratio of aniline and DMF at the initialization were investigated from 1:1 to 1:7(Fig.3).The results indicated that, with the increase of the initial molar ratio of aniline and DMF, the reaction rate kept increasing.For example, the conversion of aniline increased rapidly from 57.857%to 74.029%within 20 h with the molar ratio ranking from 1:1 to 1:6.However,there was only a tiny change in the conversion of aniline when the molar ratio was raised from 1:6 to 1:7, which could be attributed to the concentration decrease of aniline.It suggested that further increase of DMF have little effect on the conversion of aniline.Thus, the molar ratio 1:6 was considered to be the optimal.

3.4.Optimization of reaction temperature

The effect of temperature ranking from 408.15 K to 428.15 K on the conversion ofN-formylation reaction of aniline was investigated with 20% (mol) [Bsmim][HSO4] as catalyst and 1:6 as the ratio of aniline to DMF.As shown in Fig.4,the conversion of aniline increased rapidly with the raise of reaction temperature and reached the maximum value at 423.15 K.It can be explained that with the increase of reaction temperature,the number of activated molecules increased and the reaction was accelerated.However,as the reaction temperature was further increased to 428.15 K, the conversion of aniline decreased, which might be attributed to the fast volatilization of DMF at higher temperature.Therefore,423.15 K should be chosen as the appropriate temperature.

Fig.3. Effects of initial molar ratio of aniline and DMF(SBAIL type:[Bsmim][HSO4];temperature: 423.15 K; catalyst loading: 20% (mol).

Fig.4. Effects of different reaction temperature (SBAIL type: [Bsmim][HSO4];catalyst loading: 20% (mol); initial molar ratio of aniline and DMF was 1:6).

4.The Reaction Kinetics

TheN-formylation reaction kinetics of aniline with DMF was performed at 408.15,413.15,418.15,423.15 and 428.15 K,respectively (molar ratio of aniline to DMF was 1:6 and the SBIL catalyst loading was 20%(mol)).

The reaction equation for theN-formylation reaction of aniline with DMF can be written as follows:

Because theN-formylation reaction of aniline is irreversible,the reaction rate equation can be represented as follows:

whereris reaction rate,kis the kinetic constant for the reaction,CAandCBare the concentrations of aniline and DMF respectively, and the reaction orders of aniline and DMF are represented bymandnrespectively.

4.1.Determination of reaction orders

The reaction orders were determined by initial concentration method [26].Take the determination of the reaction order of aniline(m) as example:

By derivation, Eq.(1) becomes

WhenCBis far larger thanCA,nlnCBcan be regarded as a constant.ForCA=CA0(1-x),CB?CA, Eq.(2) becomes

whereCA0is the initial concentration of aniline,xis the conversion of aniline.

Set up a series of experiments with different initial concentration of aniline, whereCBwas far larger thanCA, and measure the concentration of aniline against time (Fig.4).The initial reaction ratesat different initial concentration can be measured from Fig.5.PlottingversuslnCA0, a straight line with the slope ofm(the reaction order of aniline)can be obtained from Eq.(3) and are shown in Fig.6.And the value ofm(the reaction stage of aniline) was determined to be 1.217.

Fig.5. Initial reaction rate (r =) tests of aniline at different molar ratio of aniline and DMF (SBAIL type: [Bsmim][HSO4]; temperature: 423.15 K; catalyst loading: 20% (mol)).

Fig.6. Variation of initial reaction rate of aniline with initial concentration of aniline.

Similarly,the reaction order of DMFncan also be determined in this way and the results are shown in Fig.7 and Fig.8.The value ofnwas tested to be 1.954.

Fig.7. Initial reaction rate(r =)tests of DMF at different molar ratio of aniline and DMF (SBAIL type: [Bsmim][HSO4]; temperature: 423.15 K; catalyst loading:20% (mol)).

Fig.8. Variation of initial reaction rate of DMF with initial Initial concentration of DMF.

4.2.Determination of reaction kinetics

Therefore, the kinetic model of theN-formylation reaction of aniline were determined to be:

The reaction rate constantkat different temperatures was integrated using a fourth-order Runge-Kutta method and the results are presented in Table 2.

The reaction rate constantkcan be described by the Arrhenius law (Eq.(5)) as follows:

Eq.(5) can be changed into Eq.(6):

whereA0is the pre-exponential factor andEais the reaction activation energy.

From the data in Table 2,an Arrhenius plot(Fig.9)of lnkversus(T-1) is graphed by mapping the five data points onto Eq.(6) and the value ofEawas tested to be 44.880 kJ?mol-1.

Table 2Reaction rate constants at different temperatures

Fig.9. Arrhenius plot for the N-formylation reaction of aniline with DMF using[Bsmim][HSO4] as catalysts.

5.Recycling of Catalyst

In the reaction system with room temperature ionic liquids as the catalysts or the mediums,the separation of the products needs to go through extraction and other steps, which is not only timeconsuming and difficult to industrialize, but also may introduce impurities.During the experiments, it was discovered that the SBAIL [Bsmim][HSO4] was a kind of temperature-controlled ionic liquid.As shown in Fig.10,the SBAIL[Bsmim][HSO4]was insoluble in the reaction mixture at room temperature and can form homogeneous catalytic system with reactants at high temperature.This superiority of [Bsmim][HSO4] can make contribution to overcome the problems of the separation process, which could bring about cost saving and higher production efficiency.

Therefore, it is easy to recycle and reuse [Bsmim][HSO4] by removing the supernatant of the cooling reaction mixture, and adding fresh reactants to react with the bottom ionic liquid.The specific method of catalyst recovery can be found in the Supplementary Material.The SBAIL [Bsmim][HSO4] was recycled 5 times to test its activity and stability under the optimal conditions(temperatures of 423.15 K, molar ratio of DMF to aniline of 6, catalyst loading of 20% (mol), and reaction time of 20 h).As can be seen in Fig.11,the results suggested that the catalyst was stable enough to be recycled.The slight loss of conversion of aniline can be attributed to the incomplete separation of [Bsmim][HSO4] from the reaction mixture.

6.Conclusions

The SBAIL [Bsmim][HSO4] was chosen as the catalyst for the kinetics study of theN-formylation reaction of aniline with DMF after comparing with various SBAILs, H2SO4and the BAIL [Bmim][HSO4].After investigations were conducted on the appropriate conditions for theN-formylation of aniline, the optimized conditions were as below: temperatures of 423.15 K, molar ratio of DMF to aniline of 6, catalyst loading of 20% (mol).The conversion of aniline reached 74.029% after 20 h under the optimized conditions.Furthermore, the SBAIL [Bsmim][HSO4] was explored to be a kind of temperature-controlled ionic liquid that was easy to be separated and environmentally friendly.

The reaction orders of aniline and DMF were tested to be 1.217 and 1.954 by initial concentration method, respectively.It indi-cated that the effect of the concentration of DMF on the reaction rate was greater than anilne.Then theN-formylation reaction of aniline was simulated using the proposed model based on the kinetic data, and the activation energies (Ea) of the reaction was determined to be 44.880 kJ?mol-1.

Fig.10. Photograph showing the temperature-controlled phase transitions of [Bsmim][HSO4].

Fig.11. The recycle test of [Bsmim][HSO4] catalyst.

In general,the SBAIL[Bsmim][HSO4]are considered to be excellent and promising catalyst for theN-formylation reaction of aniline, and the kinetic studies can also be used to provide the optimal setting for theN-formylation process.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgements

The authors are grateful for the financial support of National Natural Science Foundation of China ( 21776122) and the Fundamental Research Funds for the Central Universities.

Supplementary Material

The preparation procedure,1H NMR and13C NMR (BRUKER Ascend 400 MHz) characterization for each Br?nsted acidic ionic liquids synthesized.Supplementary data to this article can be found online at https://doi.org/10.1016/j.cjche.2021.09.009.

Nomenclature

A0pre-exponential factor, mol?g-1?L-1

Eaactivation energy, kJ?mol-1

kreaction rate constant, mol?g-1?L–1

mreaction order of aniline

nreaction order of DMF

Rgas constant, J?mol-1?K-1

Ttemperature, K

ttime, min

xconversion of aniline