Tetrahedron Letters 55 (2014) 205–208

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Tetrahedron Letters

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Improvement of the Friedel–Crafts benzoylation by using bismuthtrifluoromethanesulfonate in 1-butyl-3-methylimidazoliumtrifluoromethanesulfonate ionic liquid under microwaveirradiation

0040-4039/$ - see front matter � 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.tetlet.2013.10.155

⇑ Corresponding author.E-mail address: lenthach@yahoo.com (T.N. Le).

Phuong HoangTran, Ngoc BichLe Do, Thach NgocLe ⇑Department of Organic Chemistry, Faculty of Chemistry, University of Science, Vietnam National University, Hochiminh City 70000, Viet Nam

a r t i c l e i n f o a b s t r a c t

Article history:Received 23 July 2013Revised 13 October 2013Accepted 31 October 2013Available online 8 November 2013

Keywords:Friedel–Crafts benzoylationBismuth triflateMicrowave activationAryl ketone1-Butyl-3-methylimidazolium triflate

Bismuth trifluoromethanesulfonate (bismuth triflate) catalyzed the Friedel–Crafts benzoylation of acti-vated aromatic compounds when dissolved in 1-butyl-3-methylimidazolium trifluoromethanesulfonate([BMIM]OTf) ionic liquid. Immobilization of bismuth triflate (5 mol %) in [BMIM]OTf allowed the synthe-sis of aryl ketones in good to excellent yields with short reaction times under microwave irradiation. Thiscatalytic system was easily recovered and reused several times without any significant loss of theactivity.

� 2013 Elsevier Ltd. All rights reserved.

The Friedel–Crafts benzoylation of aromatic compounds is animportant carbon–carbon bond forming reaction in organic syn-thesis.1–5 Traditionally, this reaction is catalyzed by so-called con-ventional Lewis acids such as AlCl3, FeCl3, ZnCl2, and TiCl4 inappropriate organic solvents.6 However, more than a stoichiome-tric amount of catalyst is required and these catalysts could notbe recovered and reused after the usual aqueous work-up.6 There-fore, it is necessary to replace these traditional Lewis acids bygreener catalysts which are efficient under mild conditions.1 Inaddition, the catalysts should be reused to reduce the amount ofwaste in industrial processes.1,7

Metal triflates are efficient catalysts for Friedel–Crafts acylationof aromatic compounds.8 These triflates possess strong Lewis acid-ity, exhibit high tolerance toward water, and are easily recycledafter the reaction.9–12 Therefore, various organic reactions can becatalyzed by metal triflates under green conditions in goodyields,13 and the use of metal triflates in the green media has beendeveloped.1,8

Many papers have been focused on the use of ionic liquids (ILs)as a green alternative to volatile organic solvents.14–21 They arenon-volatile or have very low vapor pressure, exhibit high thermalstability, dissolve a range of organic and inorganic compounds andcan be recovered easily.22–24 Consequently, from the viewpoint of

green chemistry, ILs are benign reaction media for organic synthe-ses.25–30 Friedel–Crafts acylation reactions using metal triflates inILs have been studied extensively. In 2002, Ross and Xiao usedCu(OTf)2 in [BMIM]BF4 for the benzoylation and acetylation of acti-vated arenes.31 Vaultier et al. have reported the acylation of arenesusing bismuth derivatives in [EMIM]NTf2 and in [BMIM]NTf2.32

Furthermore, Li et al. showed that the Friedel–Crafts acylation offerrocene using Yb(OTf)3 in [BPy]BF4 proceeded smoothly undermild conditions,33 whilst Thompson reported a kinetic study ofthe metal triflate catalyzed benzoylation of anisole in ionic liq-uids.34 More recently, Galloni et al. reported an improvement offerrocene acylation using Sc(OTf)3 in alkylmethylimidazolium-based ionic liquids,35 and Leitner has reported continuous catalyticFriedel–Crafts acylation in the biphasic medium of an ionic liquidand supercritical carbon dioxide (scCO2).36

Microwave (MW) activation provides a valuable tool for organicsynthesis.37 MW-assisted reactions have emerged as green meth-ods which promote much faster, cleaner reactions than conven-tional heating.38–41 Microwave-assisted organic syntheses ingreen media or in the absence of solvent have received significantinterest due to simple and environmentally benign proce-dures.35,42–44

As part of our interest in the application of metal triflates in io-nic liquids as catalysts for the Friedel–Crafts benzoylation, we re-port herein the use of bismuth triflate in [BMIM]OTf as a greencatalytic system that promoted Friedel–Crafts benzoylation of

206 P. H. Tran et al. / Tetrahedron Letters 55 (2014) 205–208

aromatic compounds under microwave irradiation. To the best ofour knowledge, this is the first time this catalytic system has beenused for the Friedel–Crafts benzoylation under microwaveirradiation.

In our previous work, we found that Friedel–Crafts acylationproceeded smoothly using the Bi(OTf)3/[BMIM]PF6 catalytic sys-tem.45 Although the products were obtained in good yields withthe electron-rich substituents such as –OMe and –SMe, the cata-lytic system was not suitable for alkylbenzenes such as toluene,ethylbenzene, and xylene. Besides, the recycling of the catalyticsystem was not good under microwave irradiation and the yieldwas decreased in three consecutive cycles (from 74% to 64%), andstrongly in the fourth cycle (only 35%). In order to solve these prob-lems, we decided to use alkylmethylimidazolium triflate ([RMI-M]OTf) as an alternative to [BMIM]PF6. Kobayashi and Iwamotodemonstrated that the main reactant in the Friedel–Crafts acyla-tion when using a metal triflate as the catalyst was acyl triflate(R0COOTf), which reacts with aromatic compounds to afford thecorresponding ketones.11 Mechanistic investigations showed thatthe strong acylating agent, acyl triflate R0COOTf, is generated whenCl�of acyl chloride exchanged by TfO� of AgOTf46 or Bi(OTf)3.12,47

For this reason, TfO� plays an important role when a metal triflateis used as the catalyst for Friedel–Crafts acylation. Consequently,we decided to use bismuth triflate and [RMIM]OTf in our research.When using [RMIM]OTf as the solvent, the concentration of TfO�

increased in the reaction medium and acyl triflate (R0COOTf) wasgenerated easily. Indeed, slightly activated substrates such as tolu-ene, m-xylene, ethylbenzene, p-cymene, mesitylene, and evennaphthalene were benzoylated in good yield when compared withbismuth triflate in [BMIM]PF6.

In initial studies, we attempted to synthesize three ionicliquids: 1-butyl-3-methylimidazolium triflate [BMIM]OTf, 1-hexyl-3-methylimidazolium triflate [HMIM]OTf, and 1-octyl-3-methyl-imidazolium triflate [OMIM]OTf under microwave irradiation(Scheme 1). The procedure consisted of two steps: the firstinvolved the preparation of an alkylated bromide ionic liquid pre-cursor and the second involved an anion metathesis of alkylmethy-limidazolium bromide with lithium triflate.48 The procedure forthe preparation of these ILs is environmentally benign. Undermicrowave irradiation, the reaction was carried out in a short reac-tion time, under solvent-free conditions, and without using themolar excess of reagents. The MW-assisted reaction was carried

+ RBrBrMW, solvent-free

R= -C4H9, -C6H13, C8H17

+ LiOTfMW, solvent-free OTf

+ LiBr

NNMe NNMe R

BrNNMe R NNMe R

Scheme 1. Synthesis of alkylmethylimidazolium trifluoromethanesulfonates.

Table 1The preparation of alkylmethylimidazolium trifluoromethanesulfonates under solvent-free

Entry ILa Conditions

Step 1 Step 2

1 [BMIM]OTf 80 �C, 20 min 100 �C, 22 [HMIM]OTf 80 �C, 20 min 100 �C, 23 [OMIM]OTf 80 �C, 20 min 120 �C, 3

a [BMIM]OTf: 1-butyl-3-methylimidazolium trifluoromethanesufonate, [HMIM]OTf:methylimidazolium trifluoromethanesufonate.

b Isolated yield.

out in closed vessels using a CEM Discover monomode oven withstrict control of the temperature. The results are summarized inTable 1.

The Friedel–Crafts benzoylation of aromatic compounds withbenzoyl chloride to obtain the corresponding benzophenone deriv-atives using bismuth triflate in the presence of alkylmethylimi-dazolium trifluoromethanesulfonates was carried out undermicrowave activation.48 This catalytic system promoted the reac-tion in good yields, short reaction times, and employed simplework-up. Under microwave irradiation (120 �C, 30 min), this reac-tion provides a 98% conversion of anisole into 4-methoxybenz-ophenone in [BMIM]OTf; a lower conversion was observed when[HMIM]OTf (85%) and [OMIM]OTf (82%) were used. Six metal tri-flates (Li, Cu, Gd, La, Nd, and Pr) were also tested in [BMIM]OTf.However, Bi(OTf)3/[BMIM]OTf showed the highest activity waschosen as the catalytic system for this research. No reaction wasobserved in the absence of Bi(OTf)3 and only 77% yield of the prod-uct was obtained when [BMIM]OTf was not used. The reactionscope with respect to the arene substrate is presented in Table 2.Benzoylation of electron-rich arenes proceeded efficiently andthe corresponding products were obtained in good yields with70–95% selectivity for the p-benzoylated products (Table 2, entries1–4). Dimethoxybenzenes, dimethylresorcinol, and dimethylhy-droquinone were found to be less reactive than veratrol due to ste-ric hindrance when these substituents direct the electrophile to theortho-position (Table 2, entries 8 and 9). However, substantial ste-ric hindrance was tolerated in the benzoylation of m-xylene and p-cymene (entries 5 and 6). Interestingly, mesitylene was benzoylat-ed in excellent yields (entry 10). Under microwave irradiation,naphthalene was also benzoylated in good yields (entry 11). Fur-thermore, the reactivity of the catalytic system was also examinedunder conventional heating (oil bath) in the benzoylation of sub-strates such as veratrole, dimethylresorcinol, dimethylhydroqui-none, mesitylene, and naphthalene; however, the yields were notas good as those under the microwave irradiation (Table 2, entries7–11). A similar yield was obtained in the case of benzoylation ofdimethylresorcinol under conventional heating; however, a highertemperature was required (Table 2, entry 8).

Attempts were made to recover and reuse the catalytic systemBi(OTf)3/[BMIM]OTf. After extraction with diethyl ether, the ionicliquid layer was dried under vacuum for 90 min. The benzoylationof veratrol was run for three consecutive cycles at 80 �C for 15 minunder microwave irradiation. The isolated yields were slightly de-creased after each cycle (88%, 86%, and 83%). Under conventionalheating, the catalytic system was also run for three consecutive cy-cles at 120 �C for 30 min (82%, 83%, and 79% isolated yields). Theslightly decreased activity after each cycle showed that Bi(OTf)3/[BMIM]OTf was an efficient catalytic system for the Friedel–Craftsbenzoylation.

In conclusion, bismuth triflate in [BMIM]OTf is an efficient cat-alytic system for the Friedel–Crafts benzoylation reaction undermicrowave irradiation. Activated arenes and naphthalene werebenzoylated smoothly to give aryl ketones in good yields and in

conditions

Yieldb (%)

Microwave activation Conventional heating

0 min 96 740 min 95 760 min 87 64

1-hexyl-3-methylimidazolium trifluoromethanesufonate, [OMIM]OTf: 1-octyl-3-

Table 2Benzoylation of various aromatic compounds catalyzed by bismuth triflate in [BMIM]OTf under microwave irradiationa

Entry Areneb Temp.(�C) Time (min) Product Conversionc (%) Yieldd (%) o/m/pe

1 MeO 120 30MeO Ph

O98 94 5/0/95

2 Me 140 30Me Ph

O89 70 26/3/71

3 Et 140 30Et Ph

O92 84 23/7//70

4 MeS 120 30MeS Ph

O80 75 10/0/90

5

Me

Me140 30 Me

O

PhMe

98 82 100

6i-Pr Me

140 30

i-Pr

Me

O

Ph 82 75 79/21f

7 MeO

MeO

80 (120) 15 (30) MeOO

PhMeO

97 (87) 90 (83) 100

8 MeO

OMe

80 (120) 15 (15) MeOO

PhOMe

82 (84) 76 (75) 100

9 MeO OMe 120 (120) 30 (30)

MeO

OMeO

Ph98 (77) 80 (76) 100

10 Me

Me

Me

140 (140) 30 (30) MeO

PhMe

Me

99 (82) 95 (78) 100

11 140 (140) 30 (30)

O

Ph 84 (46) 76 (30) 83/17g

a Reaction conditions: arene (1 mmol), benzoyl chloride (2 mmol), bismuth triflate (0.05 mmol), [BMIM]OTf (0.1 g), MW (CEM Discover, closed-vessel). Values in paren-theses are those conditions employed and the results obtained under conventional heating.

b Low boiling point substrates such as benzene were not convenient for use, no product was obtained with deactivated substrates such as halobenzenes and nitrobenzene.c Conversion based on the arene was determined by GC using hexadecane as an internal standard.d Isolated yield.e Determined by GC.f 2-Isopropyl-5-methylbenzophenone/5-isopropyl-2-methylbenzophenone = 79/21.g 1-Benzoylnaphthalene/2-benzoylnaphthalene = 83/17 (the same selectivity was observed under both microwave activation and conventional heating).

P. H. Tran et al. / Tetrahedron Letters 55 (2014) 205–208 207

short reaction times. The catalytic system Bi(OTf)3/[BMIM]OTf isstable to moisture and could be easily recovered and reused with-out any significant loss of the catalytic activity.

Acknowledgment

We are grateful to Nafosted (National Foundation for Scienceand Technology Development—Vietnam) for financial supportthrough contract No. 104.01-2010.34.

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(0.4105 g, 5 mmol), 1-bromobutane (0.6850 g, 5 mmol) was heated undermicrowave irradiation (or conventional heating) in a 10 mL pressurized glasstube fitted with a Teflon-coated septum at 80 �C for 20 min. Then, LiOTf (0.78 g,5 mmol) was added and the mixture was irradiated at 100 �C for 20 min. Aftercooling, the mixture was diluted with MeCN (5 mL), and after removal of theprecipitated salt LiBr, the filtrate was then filtered through Celite. The crudeproduct was washed with Et2O and concentrated to give a colorless to paleyellow liquid (1.382 g, 96% yield). The [BMIM]OTf was dried under reducedpressure. The purity and authenticity of the ionic liquids were confirmed by 1Hand 13C NMR spectroscopy.Typical procedure for the benzoylation reaction in ionic liquids: a glass tube wasfilled with Bi(OTf)3 (0.0328 g, 0.05 mmol), [BMIM]OTf (0.1 g), anisole (0.108 g,1 mmol), and benzoyl chloride (0.281 g, 2 mmol) and reacted at 120 �C for30 min under microwave activation. After cooling, the mixture was extractedwith Et2O (3 � 20 mL). The organic layer was decanted, washed with water(10 mL), aqueous NaHCO3 (2 � 20 mL), brine (10 mL), and dried over MgSO4.The solvent was removed using a rotary evaporator. Conversion wasdetermined by GC analysis using n-hexadecane as the internal standard. Theisolated yield was determined after purification by flash chromatography (n-hexane, then 10% EtOAc in n-hexane) to give 4-methoxybenzophenone(0.1993 g, 94% yield). The purity and authenticity of the product wereconfirmed by GC–MS and 1H NMR spectroscopy.The same procedure was carried out under conventional heating method.