Experimental and theoretical study on N-hydroxyphthalimide and its derivatives catalyzed aerobic oxidation of cyclohexylbenzene

Yufei Yang,Jieyi Ma,Junyan Wu,Weixia Zhu,Yadong Zhang,2,*

1 School of Chemical Engineering,Zhengzhou University,Zhengzhou 450001,China

2 Jiyuan Research Institute,Zhengzhou University,Jiyuan 459000,China

Keywords:N-hydroxyphthalimide Aryl-substituted derivative Cyclohexylbenzene Oxidation Radical

ABSTRACT The liquid phase oxidation of cyclohexylbenzene (CHB) is a new green synthetic approach to cyclohexylbenzene-1-hydroperoxide (CHBHP),a key intermediate for preparing phenol and cyclohexanone.In this work,aryl-substituted (Cl and Br) derivatives of N-hydroxyphthalimide (NHPI) were synthesized and their catalytic performances for CHB oxidation were studied.In addition,geometric optimization and transition state search were performed using DFT calculations.Both experimental and theoretical studies have proven that chloro-substitution on NHPI can significantly improve its catalytic effects on the oxidation of CHB by oxygen.Compared with NHPI,CHB conversion and selectivity of CHBHP over Cl4NHPI were increased by 10.47% and 13.24%.The strategy of aryl -substituting NHPI with halogen atoms proposed in this study would provide a potential way to the development of new NHPI-based catalysts for aerobic oxidation reactions.

1.Introduction

The liquid phase oxidation is significant kind of reactions in organic synthesis.Phenol is an important raw material for the production of bisphenol A,phenolic resin,adipic acid [1,2],conventionally obtained by oxidation of cumene with oxygen and subsequently decomposition under acidic conditions[3–7].Phenol also could be producedvialiquid phase oxidation and subsequent decomposition process by using cyclohexylbenzene (CHB) as the starting reactant.This synthetic route could generate another product,cyclohexanone,which is widely applied to produce various compounds,such as caprolactam[8],ε-caprolactone[9–12],adipic acid [13],etc.The liquid phase oxidation of CHB to cyclohexylbenzene-1-hydroperoxide (CHBHP) is a new economically alternative method for the green production of phenol and cyclohexanone,which has attracted increasing attention and has become a research hotspot [14,15].

The catalytic oxidation of CHB with oxygen is of great industrial importance,but it is still the challenge to achieve high conversion efficiency and selectivity.Therefore,it is particularly important to seek more effective catalysts.At present,N-hydroxyphthalimide(NHPI) is considered to be a very representative and efficient catalyst for oxidation reaction [16–19],which can generate the corresponding phthalimideN-oxyl radical (PINO) with the aid of initiator.The catalytic system with NHPI as the active center has attracted much attention in the field of catalytic oxidation of hydrocarbons [20–25].

NHPI is a catalyst that can be used as an electron-transporting intermediate.Through single-electron transfer,the O—H bond is split to produce a highly electrophilic phthalimideN-oxyl radical(PINO) which can transform into NHPI by abstracting a hydrogen from the C—H bond of hydrocarbons,subsequently the formed carbon radical generates the hydroperoxide with the help of molecular oxygen,which accordingly initiates a radical chain reaction and completes the catalytic oxidation process of hydrocarbons under mild conditions.The reaction mechanism for the above course is shown in Fig.1 [17,26].

Fig.1.Mechanism of hydrocarbon oxidation catalyzed by NHPI.

Although NHPI plays a significant role as catalyst in radical oxidation reaction,there are still some deficiencies for NHPI,such as decomposition under high temperature and poor solubility in non-polar solvents [18],which limit its industrial applications to a great extent.To solve these problems,researchers have tried to optimize the structure of NHPI by introducing certain functional groups.A number of NHPI derivatives containing N—OH have been reported as the catalyst for oxidation reactions,i.e.,N-hydroxy-3,4,5,6-tetraphenylphthalimide (NHTPPI) [27],N-hydroxsaccharin(NHS) [28],N,N’-dihydroxypyromellitimide (NDHPI) [29,30],N-hydroxyquinolinimide(NHQI) [31],Lipophilic derivatives of NHPI [32,33],N,N′,N′′-trihydroxyisocyanuric acid (THICA) [34].Evan studied the formation of tetra-chlorophthalimidoN-oxyl radical species at two reticulated vitreous carbon electrodes and the process of producing ketene from olefin substrates[35].Mark studied the generation of tetrachloro-phthalimido-N-oxyl at a glassy carbon electrode and discussed the oxidation model of primary and secondary alcohols,specially explored the reaction rates and mechanism [36].In this work,we demonstrated two novel NHPI derivatives,tetrachloro-N-hydroxyphthalimide (Cl4NHPI) and tetrabromo-N-hydroxyphthalimide (Br4NHPI) (Fig.2),as effective catalysts for the oxidation of CHB under mild conditions.The catalytic performances of these two NHPI derivatives for the oxidation of CHB with oxygen were evaluated.And geometric optimization of structure and calculation were carried out at the DFT level with the ADF2016 suite of programs.

2.Experimental

2.1.Materials and methods

Hydroxylamine hydrochloride was purchased from Shanghai Macklin Biochemical Technology Co.,Ltd.Phthalic anhydride,triethylamine,3,4,5,6-tetrachlorophthalic anhydride,cyclohexylbenzene,3,4,5,6-tetrabromophthalic anhydride were obtained from Rhawn reagents of Shanghai Yien Chemical Technology Co.,Ltd.Ethanol,acetonitrile,acetic acid glacial,chromatography acetonitrile,and sodium acetate anhydrous were supplied by Tianjin Sailboat Chemical Reagent Technology Co.,Ltd.All the above chemicals were obtained from commercial sources and used directly.

FT-IR spectra of the compounds were determined on a ThermoNicolet IR 200 infrared spectroscopy spectroscope.1H NMR and13C NMR spectra were performed on a Bruker ADVANCE III 400 spectrometer with DMSO as the solvent.MS spectra of compounds were recorded on CESI-8000 Triple TOF 6600 time-of-flight mass spectrometer.GC–MS spectrum of CHB oxidation reaction mixture reduced by triphenylphosphine was depicted by Agilent 7000D GC/TQ.

2.2.Catalyst synthesis and characterization of the catalysts

2.2.1.N-hydroxyphthalimide (NHPI)

Phthalic anhydride (14.81 g,0.10 mol) and hydroxylamine hydrochloride (8.34 g,0.12 mol) were added to the flask and dissolved in absolute ethanol (100 ml).The solution was stirred at room temperature for 0.5 h and then refluxed for 4 h after the addition of triethylamine (12.14 g,0.12 mol).The mixed solution was washed with distilled water and filtered to get a white powder which was dried under vacuum at 60 °C.After that the solid was recrystallized from ethanol to provide the product NHPI (Yield,95.39%).IR (KBr) cm-1:3143,1790,1740,1482,1464,1384,1188,781 cm-1;1H NMR (400 MHz,DMSO-d6) δ:10.82 (s,1H),7.84 (s,4H);13C NMR (151 MHz,DMSO-d6) δ:164.68,135.08,129.03,123.44.

2.2.2.3,4,5,6-Tetrachloro-N-hydroxyphthalimide (Cl4NHPI)

3,4,5,6-Tetrachlorophthalic anhydride (5.72 g,0.02 mol) and hydroxylamine hydrochloride (1.67 g,0.024 mol) were mixed in acetic acid glacial (100 ml).After the obtained mixed solution was stirred at room temperature for 0.5 h,the sodium acetate anhydrous (1.97 g,0.024 mol) was added to the above system,which was refluxed for 6 h.Then the cooled mixture was washed with distilled water and filtered to give the powder which was dried under vacuum at 60 °C.The solid was recrystallized from ethanol to provide the product Cl4NHPI (Yield,85.77%).IR (KBr)cm-1:3584,3499,1777,1719,1361,1304,1197,792,728 cm-1;13C NMR (151 MHz,DMSO-d6) δ:160.45,138.64,128.44,126.13;MS (m/z):299.8324,297.8344.

Fig.2. N-hydroxyphthalimide and its aryl-substituted derivatives.

2.2.3.3,4,5,6-Tetrabromo-N-hydroxyphthalimide (Br4NHPI)

Br4NHPI was generated [37] by dissolving 3,4,5,6-tetrabromophthalic anhydride (9.27 g,0.02 mol) and hydroxylamine hydrochloride (1.67 g,0.024 mol) in acetic acid glacial(200 ml).After the obtained mixture solution was stirred at room temperature for 0.5 h,the sodium acetate anhydrous (1.97 g,0.024 mol) was added to the above system,which was refluxed for 6 h.Then the cooled mixture was washed with distilled water and filtered to give the powder which was dried under vacuum at 60 °C.After that the solid was recrystallized from ethylacetate to provide the product Br4NHPI (Yield,78.97%).IR (KBr) cm-1:3242,1178,1715,1373,1331,1170,772,661 cm-1;13C NMR(151 MHz,DMSO-d6) δ:160.76,136.66,128.95,120.69;MS (m/z):477.6569,475.6582.

2.3.Catalytic procedures and analysis

An acetonitrile (7.39 g,0.18 mol) solution of CHB (2.40 g,0.015 mol) and the prepared catalyst (0.0015 mol) were placed in a 100 ml three-necked flask equipped with a condenser and O2inlet tube.The reactions were performed at 80°C in an oxygen atmosphere introduced continuously at constant speed 100 ml?min-1and bubbled into the mixture for 4 h.After that,the oxidation reaction mixture was cooled down and the catalyst separated from that by centrifugation.Taking out 0.1 g solution and diluting to 10 ml with acetonitrile,which was identified using Shimadzu LC-20A HPLC monitor to determine the percentage of selectivity and conversion.

Considering the instability of CHBHP,GC is not suitable for detection the product because of decomposition at high temperature.There are some methods for the analysis of cyclohexylbenzene oxidation reaction system.Aoki [20] analyzed the products obtained from the decomposition of CHBHP using GC and didn’t mention the analysis of CHBHP.Arends [14] reduced the CHBHP in the oxidation system with triphenylphosphine and then analyzed by GC.In this article,1-phenylcyclohexanol produced by the reduction of CHBHP with triphenylphosphine was analyzed using HPLC (Fig.S10).CHBHP was calculated according to 1-phenylcyclohexanol for the first time and prepared standard solution analyzed by HPLC.The HPLC analysis was carried out using C18 column (250 mm × 4.6 mm × 5 μm) and ultraviolet detector with a detection wavelength of 210 nm.The mobile phase was H2O/ CH3CN (39/61,v/v)at a flow rate of 1 ml?min-1.The analysis time was 60 min.

The mixture of CHB oxidation reaction (0.1 g) was diluted to 10 ml with acetonitrile.After the triphenylphosphine was added,the reaction of CHBHP carried out at room temperature.Then the solution of 1-phenylcyclohexanol and triphenylphosphine oxide was obtained (Fig.S10) and diluted with ethyl acetate solvent.The components of the products were analyzed by GC–MS shown in Fig.S11.

2.4.Procedure for computer DFT methods

All of the calculations were fulfilled at the DFT level with ADF2016 suite of programs [38,39].The exchange and correlation energies were calculated using the PBE density functional within the framework of the generalized gradient approximation (GGA).The basic functions to describe the valence electrons of each atom were triple-ξ plus polarization Slater basis sets (TZP) which described by single Slater function.The zero-order regular approximation (ZORA) [40,41]was used in all of the calculations to illustrate the scalar relativistic effect.Full geometry optimizations were performed on each structure in the presence of the conductor-like screening solvent model(COSMO) [42,43] with acetonitrile as solvent.The ionic radii for the atoms,which actually defined the cavity in the COSMO,were 0.170,0.135,0.1517,0.1608,0.1725 and 0.185 nm for C,H,O,N,Cl and Br,respectively.The value of the numerical integration parameter used to determine the accuracy of numerical integrals was 5.5.Spin-unrestricted calculations were carried out for all of the open-shell systems.Full details,including coordinates for all stationary points,computed energy barriers and reaction enthalpy,as well as summary tables can be found in the data section.

3.Results and Discussion

3.1.Oxidation reactions of CHB by catalysts

The catalysts of NHPI,Cl4NHPI and Br4NHPI can be facilely synthesizedviaone-step method using the corresponding anhydride and hydroxylamine hydrochloride as the starting material.The stability of aryl-substituted derivatives performed in cyclohexylbenzene oxidation reactions was higher in the presence of NHPI.The catalytic oxidation performance of NHPI,Cl4NHPI and Br4NHPI for CHB was carried out under the same conditions.CHBHP could be obtained along with small amounts of 1-phenylcyclohexene,phenylhexanone and 1-phenylcyclohexanol.CHB oxidation reaction mixture reduced by triphenylphosphine was analyzed qualitatively on the basis of GC–MS.The results were shown in Fig.S11.The retention times of CHB,1-phenylcyclohexene,phenylhexanone and 1-phenylcyclohexanol were 9.163,9.710,10.080,10.309,respectively.NIST MS database gave a good match for the spectra of CHB (CAS:827-52-1,NITS:228262),1-phenylcyclohexene (CAS:771-98-2,NITS:334900),phenylhexanone (CAS:942-92-7,NITS:456667) and 1-phenylcyclohexanol(CAS:1589-60-2,NITS:243988).As shown in Table 1,the conversion rate of CHB was very low without catalyst.When NHPI was used in this reaction,the conversion rate was increased to 50.85% with 78.13% selectivity to CHBHP.The addition of NHPI aryl-substituted derivatives resulted in an increase catalyst performance in both the conversion rate of CHB and the selectivity to CHBHP under the same conditions.In the presence of Cl4NHPI,CHB conversion and selectivity of CHBHP increased by 10.47%and 13.24%,respectively,compared with NHPI.When Br4NHPI was used as catalyst,the CHB conversion was reduced by 9.56%but the selectivity to CHBHP increased by 7.48%.In addition,the effects of solvents on the reaction were also investigated including polar protic solvents of ethanol and acetic acid and nonpolar protic solvents of ethyl acetate and acetonitrile.The oxidation reaction activity of CHB under different solvents at the same reaction condition was shown in Table 1.

Table 1 Oxidation activity of CHB catalyzed by the catalysts of NHPI,Cl4NHPI,Br4NHPI in different solvents

When ethanol used as the solvent,there was no CHBHP produced.The possible reason was that the protic solvent caused the formation of intermolecular hydrogen bond between the alcoholic hydroxyl group and catalysts,which increased the dissociation energy of O—H,resulting inN-oxyl radicals unstable and catalytic reactivity reduced.Therefore,alcoholic solvents cannot initiate CHB oxidation due to the presence of alcoholic hydroxyl groups.However,carboxylic acid protic had a certain degree of inhibition on the formation of intermolecular hydrogen bonds,and the conversion rate increased to 12.38%.Ethyl acetate was an aprotic solvent,and its ester group could form an intermolecular hydrogen bond with the O—H of catalyst,but which would be weakened because of the steric hindrance effect.Hence,N-oxyl radicals could be generated to initiate radical reaction,and the conversion reached to 23.95%.Among these studied solvents,acetonitrile was the best choice for the catalytic oxidation of CHB.

As described previously,the catalytic oxidation activity of CHB was determined by the hydrogen absorption capacity of the intermediateN-oxyl radicals [44,45].Espenson has confirmed that the O—H bonds of NHPI aryl-substituted derivatives were strengthened by electron-withdrawing groups,such as halogens Cl and Br.Therefore,the hydrogen abstraction ability of PINO substituted by electron-withdrawing groups would be higher than those of PINO substituted by electron-donating groups [46].In this article,we synthesized the compounds NHPI and its ring-substituted derivatives with halogen.The O-H bond of compounds may be enhanced due to a strong electron-withdrawing effect of halogen substitution,and thus the H-atom abstraction ability of the active intermediate PINO was increased.The most direct experimental result was that the catalytic activity of Cl4NHPI for CHB oxidation was higher than that of NHPI.However,Br4NHPI showed lower reactivity than NHPI,which can be ascribed to the instability of the corresponding Br4PINO resulting from strong electronwithdrawing groups of bromine.

3.2.Calculations of oxidation reactions by catalysts

Fig.3.Reaction Mechanism for the CHB oxidation catalyzed by NHPI,Cl4NHPI and Br4NHPI.

Fig.4.Reaction profile abstracted H from CHB for the mechanism at 80°C in acetonitrile as solvent(Fig.3(b)).Optimized structures of the transition state obtained with ADF at the level of PBE-D3/TZP.Energy barriers (kcal?mol-1) of reaction and bond length (?) of the transition state are given (1 kcal=4.186 kJ,1 ?=0.1 nm).

In order to gain further insight into the reaction mechanism of CHB oxidation utilizing NHPI and its ring-substituted derivatives as the catalysts,a DFT study was performed.As mentioned previously,the process ofN-oxyl radicals capturing the H-atoms of the substrate is an important process in the catalytic oxidation of the substrates [47–49].Therefore,we mainly calculated and analyzed the effect on CHB H-abstraction process by theN-oxyl radicals generated from synthesized compound(Fig.3(b))and the formation of CHBHP from cyclohexylbenzeneperoxy radicals (Fig.3(d)).The influence of the solvent and temperature was considered.For all systems,the calculations included that the Gibbs free energy and enthalpy of the reactants,transition states (TS) and products.Fig.4 depicted the optimized structure of reaction path and energy barriers.There is little difference in the geometrical parameters for the transition state of catalysts.Aryl substitution with strong electron-withdrawing halogens makes the O—H bond longer and the N—O bond shorter.The H-abstraction from CHB byN-oxy radicals is an important process in the overall oxidation utilizing catalysts.Herein,the relative reactivity of the correspondingN-oxy radicals capturing H-atom of CHB was evaluated.The order of the H-abstraction energy barriers was as follows:(Br4NHPI >NHPI >Cl4NHPI).The reactivity of Cl4NHPI is the highest because of the lowest energy barriers.Besides,the improved catalytic efficiencies of Cl4NHPI and Br4NHPI compared to that of NHPI can be ascribed to the lower energy barriers and the endothermicity in the H-abstraction processes from CHB by their corresponding radicals,especially by their ring-benzene substituted with halogens which show stronger electron-withdrawing effects.As mentioned above,the experimental and calculation results are also consistent.

And another research focus is the formation of CHBHP from cyclohexylbenzeneperoxy radicals (Fig.3(d)) which determines the length of propagation and the rate of reaction [14].Fig.5 depicts the optimized structure of reaction path,and provides the energy barriers and bond length of the transition state.The CHBHP radicals efficiently trap an H-atom from NHPI or its derivatives to form the production CHBHP and correspondingN-oxy radicals for the cycle of Fig.3.The reactivity of these catalysts follows the order Cl4NHPI>NHPI>Br4NHPI,which is contrary to the order of the energy barrier.Taking the influence of the solvent and the influence of the electron-withdrawing effect of aryl substitution on the catalyst into account,Cl4NHPI exhibits the highest reactivity for catalyzing the oxidation reaction of CHB to generate CHBHP in acetonitrile.

Fig.5.Reaction profile formed for the mechanism of CHBHP at 80°C in acetonitrile as solvent(Fig.3(d)).Optimized structures of the transition state obtained with ADF at the level of PBE-D3/TZP.Energy barriers (kcal?mol-1) of reaction and bond length (?) of the transition state are given (1 kcal=4.186 kJ).

4.Conclusions

In this work,we have studied the aerobic oxidation of CHB to CHBHP by utilizing NHPI,Cl4NHPI and Br4NHPI as the catalysts.Among them,Cl4NHPI displayed the best catalytic activity.Simultaneously,the theoretical calculation of reaction mechanism of CHB oxidation were performed,which realized that the catalytic oxidation of CHB was determined by the hydrogen absorption capacity of the intermediateN-oxyl radicals.The relative reactivity of the correspondingN-oxy radicals capturing H-atom of CHB was determined by H-abstraction energy barriers.The aryl of PINO substituted by electron-withdrawing group chlorine can enhance the H-atom abstraction activity.In summary,considering the effects of the solvent and the electron-withdrawing effect of arylsubstitution on the catalyst,it can be concluded that Cl4NHPI showed the highest reactivity in the oxidation of CHB in acetonitrile.The present work not only extended the application of Cl4-NHPI for the catalytic oxidation of organic compounds and also provided a potential way to the development of new NHPI-based catalysts for aerobic oxidation reactions.

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

This work was financially supported by the National Natural Science Foundation of China (21706240).We would like to acknowledge all the reviewers for their valuable suggestions and Prof.Fuqiang Zhang of School of Chemistry and Material Science in Shanxi Normal University for DFT calculations.

Supplementary Material

Supplementary data to this article can be found online at https://doi.org/10.1016/j.cjche.2021.06.017.