Synthesis of 1-acetylpyrene via Friedel-Crafts Reaction Using Chloroaluminate Ionic Liquids as Dual Catalyst and Solvent

Ying Luo, Aixia Pan, Min Xing, Min Chen*, Jimin Xie

School of Chemistry and Chemical Engineering, Jiangsu University,

301 Xuefu Road, Zhenjiang 212013, Jiangsu, PR China

Chenmin3226@sina.com

Keywords: 1-acetylpyrene, Friedel-Crafts acylation, chloroaluminate ionic liquid, [Emim]Cl-AlCl3

Abstract. Acetylation of pyrene with acetyl chloride to 1-acetylpyrene catalyzed by chloroaluminate

ionic liquids of different alkyl chain length and metal chloride was investigated. Pure 1-acetylpyrene

was obtained and the structure of 1-acetylpyrene was identified by GC/MS, FT-IR and 1HNMR

spectra.[Emim]Cl/AlCl3([Emim]+=1-ethyl-3-met-hylimidazolium cation) ionic liquid was found to

be the most active catalyst in the acylation. The yield of 1-acetylpyrene was up to 91.8% and the

selectivity towards 1-acetylpyrene was up to 98.2%. The reusing experiment shows that

[Emim]Cl-AlCl3 can be used as both catalyst and solvent, and it is reusable and environmentally

friendly for the preparation of 1-acetylpyrene.

Introduction

Friedel-Crafts acylation of aromatic compounds is an ubiquitous reaction in the production of

aromatic ketones，and largely used as intermediates in the synthesis of fine and speciality chemicals

as well as pharmaceuticals. To date, acylations of benzene and naphthalene have been thoroughly

investigated and widely used in the industry. 1-acetylpyrene is condensed with N-alkylated

indole-3-carboxaldehydes to yield the ethylenic compounds, which are considered as significant

drugs, since 1-acetyl- pyrene were examined for possible antiviral activity against HIV-1 using

MT-4 cells astarget cells[1].

However, the current Friedel-Crafts acylation uses highly corrosive and potentially lethal acids,

such as aluminium trichloride (AlCl3) and hydrofluoric acid (HF), both of which are not easily

recovered with the release of environmentally unfriendly effluents. Further- more, these Lewis acids

are consumed in more than stoichiometric amounts due to the formation of 1:1 molar adduct with

aromatic ketones and the subsequent separation of the product by hydrolysis, which is cumbersome,

generates a large amount of hazardous, corrosive, environmentally unfriendly waste approximately

more than 4 mol of Cl- per mole of the ketone produced. The major drawback in this process is that

the Lewis acid is non-regenerable[2].

In recent years, ionic liquids(ILs) have attracted increasing interest and been success- fully used

as environmentally benign catalysts and solvents in a variety of catalytic reactions due to their

relatively low viscosities, low vapor pressure, high thermal, and chemical stability, etc[3-5]. Wilkes

first reported the Friedel- Crafts reactions of aromatic substrates, such as benzene, toluene,

chlorobenzene, and nitro- benzene, in ILs[6]. To date, Friedel-Crafts acetylations of benzene,

naphthalene, and their derivatives catalyzed by ILs have been given considerable attention.

Acetylations of some polyaromatics, such as naphthalene, pyrene, phenanthrene and anthracene, in

ILs were also investigated[7]. But the yield of 1-acetylpyrene reported was only 13% around[7]. In

our laboratory, we have researched Friedel-Crafts acylation of anthracene, acenaphthene. Hence, in

order to obtain the higher yield and selectivity of 1-acetylpyrene, we studied the catalytic properties

of six kinds of Lewis acids. The effects of varying reaction conditions on the synthesis of

1-acetylpyrene in the selected ionic liquids were extensively studied. To the best of our knowledge,

no acetylation of pyrene with acetyl chloride catalyzed by different ILs has been reported.

Advanced Materials Research Vols. 443-444 (2012) pp 917-922Online available since 2012/Jan/03 at www.scientific.net© (2012) Trans Tech Publications, Switzerlanddoi:10.4028/www.scientific.net/AMR.443-444.917

All rights reserved. No part of contents of this paper may be reproduced or transmitted in any form or by any means without the written permission of TTP,www.ttp.net. (ID: 130.194.20.173, Monash University Library, Clayton, Australia-01/10/13,06:54:42)

In the present paper, the catalytic activities of Lewis acidic ILs such as [Emim]Cl-AlCl3,

[Bmim]Cl-AlCl3 and [Omim]Cl-AlCl3 ([Bmim]+

=1-butyl-3-methylimidazolium cation, [Omim]+

=1-octyl-3-methylimidazolium cation), in the acetylation of pyrene with acetyl chloride to

1-acetylpyrene(Scheme 1) were investigated under different experimental conditions. The Lewis

acidic ILs were easily isolated from the products and effectively recycled.

catalyst

COCH3

CH3COCl

Scheme 1. Friedel-Crafts acetylation of pyrene to 1-acetylpyrene

Experiments

Materials

N-Methylimidazole was obtained from the Alfa Aesar company and 1-ethyl-3-methyl imidazolium

chloride([Emim]Cl) was purchased from Institute of Chemistry & Chemical Engineering, Hebei

Normal University and used without further purification. Alkyl halides were of Chemical Grade

from Shanghai Reagent Company(Shanghai, China) and were used as such. All other chemicals

used in this study were commercially available and were used without further purification.

Preparation of Ionic Liquids

The precursors 1-butyl-3-methylimidazolium chloride([Bmim]Cl) and 1-octyl-3-methylimida-

zolium chloride ([Omim]Cl) were synthesized according to the literature. All the aluminum ionic

liquids(Al-IL) were synthesized by using the method reported in the literature[8].The typical

procedure is illustrated in Figure 1.

N

N

Me

RCl

NN

MeR

2AlCl3

Cl-

NN

MeR

Al2Cl7-

Figure 1 Typical procedure of ionic liquids preparation

Acetylation of pyrene with acetyl chloride

Given amounts of pyrene and acetyl chloride were put into a 100 mL three-neck flask equipped

with a stirrer, a reflux condenser with a drying pipe and a thermometer. Then an appropriate amount

of catalyst and solvent was added dropwise to the flask in 10 min with stirring. The acetylation

reaction was typically carried out for 3-8 h at the desired temperature and ambient atmosphere with

vigorous stirring. Then, the reaction mixtures were cooled to room temperature. The mixtures

included two liquid phases(organic phase and ionic liquid phase); ionic liquid could be reused after

extracting the organic phase with ether. The yields and the selectivity of the desired product were

obtained through GC analysis in the organic phase. The crude desired product in the organic phase

was washed with distilled water and petroleum ether, respectively. Then recrystallized from

methanol to give pure product as yellow solid. Qualitative and quantitative analysis was conducted

with GC/MS (HP 6890), 1HNMR (BRUKER 600), and FT-IR (Nexus 470), respectively.

The spectral data for the desired product 1-acetypyrene: 1H NMR(500 MHz, CDCl3)，δ：2.915(s,

4H)，8.049-8.086(m, 2H, J=8.068 )，8.165-8.185 (t, 2H, J=8.170 Hz)，8.224-8.271(m, 3H)，

8.387-8.403(d, 1H, J=4 Hz)，9.061-9.080(d, 1H, J=4.75Hz)

918 Manufacturing Science and Materials Engineering

Results and Discussion

Effect of Lewis Acidic ILs

The yields and the selectivity of the alkylation of anthracene with acetyl chloride catalyzed by three

metal halides and five Lewis acidic ILs containing1-alkyl-3-methylimidazolium chloride and

different metal halides are listed in Table 1.When the reaction was catalyzed by the metal

halides,CS2 was used as a solvent.

Table 1. The catalytic activities of the Lewis acidic ILs and metal halides in the acetylation of pyrene to 1-acetypyrene

Entry 1 2 3 4 5 6

Catalyst ，，，，

mole fraction of

metal halide(x)

AlCl3 FeCl3 ZnCl2 IL1

d

0.67

IL2e

0.67

IL3f

0.67

Catalyst

loadinga

4 4 4 4 4 4

Ratio of

reactantsb

10 10 10 7 10 10

Temper.(oC) 35 35 35 30 30 30

Time(h) 5 5 5 5 5 5

Yieldc(%) 76.8 75.4 0 91.8 87.3 85.9

Selectivityc(%) 78.3 76.5 0 98.2 88.9 86.3

aThe molar ratio of catalyst to pyrene;

bThe molar ratio of acetyl chloride to pyrene;

cThe yield

and selectivity were determined by GC; d[Emim]Cl-AlCl3;

e[Bmim]Cl-AlCl3;

f[Omim]Cl-AlCl3

The experimental results show that Lewis acidic ILs containing AlCl3 had good catalytic

activities. Among all the investigated catalysts, [Emim]Cl-AlCl3 IL exhibited the best catalytic

activity with a yield of 91.8% and a selectivity of 98.2% for 1-acetylpyrene(Entry 4). On the other

hand, among three metal halides, AlCl3 had the highest catalytic activity in the acetylation of pyrene

to 1-acetylpyrene, while FeCl3 showed poor catalytic activity and ZnCl2 had no activity (Entry 1-3).

The catalytic activity order of the metal halides is consistent with that of their Lewis acidic

strengths. Although AlCl3 showed good catalytic activity in the acetylation of pyrene to

1-acetylpyrene, the procedure suffered from severe problems, such as horrible corrosion and

pollution, uneasy product purification, and impossible catalyst recycle. While Lewis acidic ILs were

used as the catalysts, the product isolation and purification was quite easier and the acetylation was

free of any volatile organic solvent since the ILs play a dual role of catalyst and solvent.

When the ILs were prepared with the same metal halide(AlCl3) and different alkyl groups, such

as [Emim]Cl-AlCl3, [Bmim]Cl-AlCl3, and [Omim]Cl-AlCl3, the catalytic activity decreased with

the chain length of N-substituted alkyl of imidazole cations (Entry4,5,6). According to the

carbenium mechanism of Friedel-Crafts acetylation reaction, Friedel-crafts alkylation reaction is

significantly influenced by the concentration and stability of the intermediate carbenium ions, and

the high molecular polarizability of the reaction medium greatly facilitates the generation of

carbenium ions. It was reported that the polarizability of the ILs deareased with increasing the alkyl

length because the longer alkyl groups can provide a more hydrophobic (hence non-polar) environ-

ment than the smaller ones can. Therefore, the molecular polarizability of the used ILs should be in

the order of [Emim]Cl-AlCl3> [Bmim]Cl- AlCl3>[Omim]Cl-AlCl3, resulting in a decrease in their

acetylation activity with increasing alkyl length. Furthermore, the imidazole ion itself shows a weak

Lewis acid and the Lewis acidic strength decreased with increasing the alky length. This is probably

another reason why the catalytic activity decreases with increasing alkyl length of the imidazole

cations.

Effects of Experimental Parameters on the Catalytic Activity of [Emim]Cl-AlCl3 Catalyst

[Emim]Cl-AlCl3 exhibited the most excellent catalytic performance with satisfactory yield and

selectivity of the desired product (entry 4, Table 1). Therefore, we chose [Emim]Cl-AlCl3 as the

high effective catalyst to further investigate the effects of experiental parameters on the catalytic

acetylation reaction and the recycling performance of the catalyst.

Advanced Materials Research Vols. 443-444 919

Effect of Molar Ratio of Ionic Liquid to Pyrene

The effect of the molar ratio of [Emim]Cl-AlCl3 to pyrene on the yield and selectivity of

1-acetylpyrene were tested and the results are shown in Figure 2. The yield and selectivity of

1-acetylpyrene increased when the molar ratio of [Emim]Cl-AlCl3 to pyrene increased from 1:1 to

4:1, then decreased as further increasing the molar ratio of [Emim]Cl- AlCl3 to pyrene. The

maximum yield and the selectivity were 91.8% and 98.2%, respectively, when n([Emim]Cl- AlCl3):

n(pyrene)=4.

Figure 2. Effects of molar ratio of ionic liquid to pyrene on the acylation of pyrene to 1-acetylpyrene

Reaction conditions: x(AlCl3)=0.67; n(acetyl chloride) n(pyrene)= 7, T= 30 ℃, t = 5 h

Effect of Molar Ratio of acetyl chloride to pyrene

Figure 3 shows the results at various mole ratios of acetyl chloride to pyrene from 1 to 13. It was

found that the yield of 1-acetylpyrene was significantly improved with increasing the molar ratio of

acetyl chloride to pyrene from 1 to 7, then no longer had obvious increase as further increasing the

mole ratios from 7 to 13. However, mole ratios of acetyl chloride to pyrene had no noticeable

influence on the selectivity towards 1-acetylpyrene. The molar ratio of acetyl chloride to pyrene of

7 favors the formation of 1-acetylpyrene.

0 2 4 6 8 10 12 1465

70

75

80

85

90

95

100

n(acetyl chloride) : n(pyrene)

Yield or selectivity

Yield%

Selectivity%

Figure 3. Effects of molar ratio of acetyl chloride to pyrene on the acylation of pyrene to 1-acetylpyrene

Reaction conditions: x(AlCl3)=0.67; n([Emim]Cl-AlCl3): n(pyrene) = 4, T= 30 ℃, t = 5 h

Effects of Reaction Temperature

The effect of reaction temperature on both yield and selectivity of 1-acetylpyrene was

investigated at reaction temperatures ranging from 10 to 60 oC (Figure 4). The results show that the

yield and selectivity of 1-acetylpyrene rapidly increased with increasing the reaction temperature

from 10 to 30oC. However, as a result of the exothermic nature of the reaction, a slight decrease in

yield and selectivity of the desired product took place when the reaction temperature was further

raised. Probably,the yield was not influenced greatly in certain extent.The suitable reaction

temperature was 30 oC.

0 1 2 3 4 5 6 7 8 9

65

70

75

80

85

90

95

100

Yield%

Selectivity%

Yield or selectivity

n(((( [EmimCl]-AlCl3)))) :n(pyrene)

0 1 2 3 4 5 6 7 8 9

65

70

75

80

85

90

95

100

Yield%

Selectivity%

Yield or selectivity

n(((( [EmimCl]-AlCl3)))) :n(pyrene)

920 Manufacturing Science and Materials Engineering

5 10 15 20 25 30 35 40 45 50 55 60

52

56

60

64

68

72

76

80

84

88

92

96

100

reaction temperature/oC

Yield or selectivity

Yield%

Selectivity%

Figure 4. Effects of reaction temperature on the acylation of pyrene to 1-acetylpyrene

Reaction conditions: x(AlCl3)=0.67; n(acetyl chloride) : n(pyrene)= 7, n([Emim]Cl-AlC13): n(pyrene) = 4, t = 5 h

Effects of Reaction Time

The influence of the reaction time for the acetylation reaction is illustrated in Figure 5. The

results show that increasing the reaction time from 1 to 5 h caused a noticeable increase in the yield

and selectivity of 1-acetylpyrene; then the yield and the selectivity decreased as further decreasing

the reaction time from 5 to 9 h (Figure 5). This is because Friedel-crafts acetylation is a reversible

electrophilic substitution reaction.In the initial stage of the reaction,1-acetylpyrene was the

predominant product because the 1-position in pyrene has maximum electron cloud

density.However,with the prolongation of reaction time, as a result of thermodynamic control of the

reaction, two-acetylations of pyrene became the superior product because of its most stable

structure.Therefore,the yield and selectivity of 1-acetylpyrene were decreased after reaction for 5 h.

0 1 2 3 4 5 6 7 8 9 1080

82

84

86

88

90

92

94

96

98

100

reaction time/h

Yield or selectivity

Yield%

Selectivity%

Figure 5. Effects of reaction time on the acylation of pyrene to 1-acetylpyrene

Reaction conditions: x(AlCl3)=0.67; n(acetyl chloride): n(pyrene)=7, n([Emim]C1-A1C13): n(pyrene) = 4, T=30 ℃

Reusability of [Emim]Cl-AlCl3

As one of the most active Lewis acidic IL catalysts, [Emim]Cl-AlCl3 was selected to investigate the

possibility of reusability. After reaction, the reaction mixtures became two liquid phases, being

organic phase (unreacted reactants and products phase) and the [Emim]Cl-AlCl3 IL phase.

[Emim]Cl-AlCl3 was reused after extracting the organic phase with ether and treated under

vacuum(0.01Torr)at 80-100oC for 30 min. The results of the acetylation catalyzed by the recycled

[Emim]Cl- AlCl3 are shown in Figure 6.After the [Emim]Cl-AlCl3 catalyst ran 5 times, the yield

and selectivity of 1-acetylpyrene were only slightly lowered as compared to the fresh catalyst.

Although the amount of IL used is much higher than the reactants, the result of the recycled use

indicates that the actual consumption of [Emim]Cl-AlCl3 in synthesis of 1-acetylpyrene has

relatively less amount. The present study shows that [Emim]Cl-AlCl3, as a recoverable catalyst and

solvent, is not only env ironmentally benign but also economical for acetylation of pyrene to

1-acetylpyrene.

Advanced Materials Research Vols. 443-444 921

1 2 3 4 5

0

20

40

60

80

100

Yield%

Run number

Figure 6. Results of repeated use of [Emim]Cl-AlCl3 catalyst

Conclusions

In summary, we successfully developed an efficient and eco-friendly Friedel-Crafts acetylation

route for the synthesis of 1-acetylpyrene using Lewis acidic IL as both catalyst and solvent under

mild conditions. [Emim]Cl-AlCl3 IL exhibited the highest catalytic activity among five used ILs.

The product and [Emim]Cl-AlCl3 IL were easily separated. [Emim]Cl-AlCl3 IL showed stable

catalytic activity after running 5 times. The use of [Emim]Cl-AlCl3 IL in the acetylation provides a

better and practical alternative to the existing procedures.

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922 Manufacturing Science and Materials Engineering

Manufacturing Science and Materials Engineering 10.4028/www.scientific.net/AMR.443-444 Synthesis of 1-Acetylpyrene via Friedel-Crafts Reaction Using Chloroaluminate Ionic Liquids as Dual

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