Titanium Dioxide-Mediated Friedel–Crafts Acylation ofAromatic Compounds in Solvent-Free Condition underMicrowave Irradiation

Mohamed Afzal Pasha, Krishnappa Manjula, andVaderapura Puttaramegowda JayashankaraDepartment of Studies in Chemistry, Central College Campus, Bangalore University, Bangalore, India

Friedel–Crafts acylation of different arenes was carried out inthe presence of titanium dioxide under microwave irradiation insolvent-free condition. Activated substrates undergo acylationpredominantly at the para-position. An efficient, simple, selectiveacylation reaction affords good yield of the products and thecatalyst could be easily recovered and recycled.

Keywords Friedel-Crafts acylation, arenes, acid chlorides, TiO2,microwave irradiation

INTRODUCTION

The Friedel–Crafts acylation of aromatic compounds is one

of the most established and useful reactions.[1] Used in a wide

variety of fields including pharmaceuticals, fragrances,

polymers, agrochemicals and in the most fundamental C–C

bond forming reactions.[2] The classical Friedel–Crafts acyla-

tion reaction is carried out by using AlCl3.[3,4] The Lewis acid

(AlCl3 or FeCl3) promoted reactions have some limitations,

such as the requirement of more than stoichiometric amount

of the Lewis acid and treatment of the AlCl3 residue after the

reactions. To minimize this problem, catalytic Friedel–Crafts

acylation was achieved by various methods developed

with methane sulfonic acid,[5] perfluorinated sulfonic

acid resin (Nafion–H),[6] HZSM–5 Zeolites,[7] heteropoly

salt Cs2.5H0.5PW12O40,[8] AIPW12O40,[9] Metal-Cation

(Mþ2Mont),[10] polymer-supported aluminum chloride,[11]

alumina,[12] triflates like Bi(OTf)3 or Sc(OTf )3,[13]

Ln(OTf)3[14] and Yb(OTf)3.[15] Recently, bismuth derivatives

such as (þ)-Bi(OTf)3 or BiOCl or Bi2O3 in the presence of

ionic liquid-[emim][NTf2],[16] metal and metal oxide like

Zn[17] and ZnO.[18] The catalytic Friedel–Crafts acylation

reactions have their own advantages and limitations, for

example, higher selectivity, easier work-up and environmental

safety are some of the advantages. Disadvantages are use of

excess acid catalyst, unsatisfactory yields, cumbersome meth-

odologies, flammability or risk of explosion of the reagents

and cost of the reagents. Thus, the search for new catalysts

and methods is still of practical importance.

Microwaves, on the other hand, accelerate the chemical

reactions in solvents as well as under solvent-free conditions,

and have witnessed an explosive growth. Microwave

irradiation often leads to shorter reaction time, increased

yields and easier work-up matching with “green chemistry”

protocols. The availability of several publications in the

literature clearly indicates the impact of microwave-assisted

reactions in organic synthesis.[19,20]

To promote the Friedel–Crafts acylation, reaction of

aromatic compounds with acid chloride, we have used TiO2,

and the corresponding acylated product is obtained in high

yields under microwave irradiation and solvent-free conditions

as shown in Scheme 1.

RESULTS AND DISCUSSION

In our laboratory we have shown that reduction of different

functional groups using metals/metal salts and/or ammonium

salts is possible, and simple metals such as Al, Zn, Sn, and Sb

can replace expensive and complex reducing agents for

reduction under different reaction conditions.[21 – 25] Now, our

interest is in the use of metal oxides in conjunction with

microwave irradiation.

Recently we have reported synthesis of 3,4-dihydropyrimi-

din-2(1H )-ones/thiones using catalytic amount of ZnCl2 via

Biginelli reaction under microwave irradiation.[26] In this

paper we report a simple, efficient and selective method for

preparation of aromatic ketones by solvent-free Friedel–

Crafts acylation reaction of aromatic compound with benzoyl

chloride and acetyl chloride in the presence of TiO2 under

Received 3 December 2005; accepted 16 January 2006.Address correspondence to Mohamed Afzal Pasha, Department of

Studies in Chemistry, Central College Campus, Bangalore University,Bangalore 560 001, India. E-mail: m_af_pasha@yahoo.co.in

Synthesis and Reactivity in Inorganic, Metal-Organic and Nano-Metal Chemistry, 36:321–324, 2006

Copyright # 2006 Taylor & Francis Group, LLC

ISSN: 0094-5714 print/1532-2440 online

DOI: 10.1080/15533170600651389

321

microwave irradiation. To find a suitable catalyst, we worked

with three different metal oxides, namely: TiO2, CdO, and

CuO under solvent-free conditions and found that metal

oxide can promote the Friedel–Crafts acylation of aromatic

compounds affording the corresponding acylated products in

satisfactory yields, as shown in Table 1.

Out of the three selected catalysts, TiO2, which is non-toxic,

inexpensive and commercially available, has been used earlier

in a one-step Beckmann rearrangement of aldehydes and

ketones in solvent-free conditions.[27] We found it to have a

remarkable activity for the Friedel-Crafts acylation. The

results of Friedel–Crafts acylation of aromatic compounds cat-

alysed by TiO2 under microwave irradiation are presented in

Table 2. Here, it is clear that aromatic compounds react very

rapidly (within 20–50 sec) to give ketones. The reactions are

clean, and easy acylation of unactivated benzenes such as

chlorobenzene also takes place, affording the corresponding

aromatic ketone in acceptable yields (Table 2, entries 2 and 8).

Acylation occurs exclusively at the position para to group

presented in the arene. We report here only the major isomer,

which has been isolated by column chromatography.

We have examined the recovery and reuse of the catalyst

on the benzoylation of toluene to get 4-methylbenzophenone

and found that the yields of the product in the second and

third use of the catalyst were almost same as that in the first

use. In every case, .90% of TiO2 was recovered by filtration,

washing with water and drying at 120 8C (Table 3).

EXPERIMENTAL

All aromatic compounds, acid chlorides and metal oxides

were purchased from BDH/MERCK and all the solvents

were distilled before use. All the reactions were carried out

using a conventional (unmodified) household microwave

TABLE 1

Friedel–Crafts acylation of chlorobenzene with benzoyl

chloride using different metal oxide under

microwave irradiation

Entry Metal oxide

Reaction

temperature

( 8C)

Time

(sec)

Yield

(%)

1 TiO2 100–103 20 70

2 CdO 105–109 30 65

3 CuO 110–113 35 60

SCH. 1.

TABLE 2

Friedel-Crafts acylation of substituted arenes with benzoyl chloride and acetyl chloride in the presence of TiO2

under microwave irradiation

Entry Substrate Product

Reaction

temp ( 8C)1Time

(sec)

Yield

(%)

m.p b.p ( 8C)

Found/reported

With benzoyl chloride

1 Benzene Benzophenone 68 25 72 46–48/48–49b

2 Chlorobenzene 4-Chlorobenzophenone 103 20 70 74–76/75–77b

3 Toluene 4-Methylbenzophenone 80 20 68 56–58/56.5–57a

4 2-Xylene 3,4-Dimethylbenzophenone 63 50 69 46–47/45– 47a

5 Naphthalene 2-Benzoylnaphthalen 70 25 65 80– 82/82c

6 1,2-Dichlorobenzene 3,4-Dichlorobenzophenone 60 30 65 103/101– 104b

With acetyl chloride

7 Benzene Acetophenone 68 35 68 201– 202/202a

8 Chlorobenzene 4-Chloroacetophenone 70 35 65 232/230–232b

9 Naphthalene 2-Acetonaphthanone 47 25 60 54–56/56c

10 Toluene 4-Methylacetophenone 45 30 65 224–226/226a

1Reaction temperature was measured by immersing a glass thermometer into the reaction mixture immediately after exposure to microwave

irradiation.aAldrich: Handbook of Fine Chemicals and Laboratory Equipment, Sigma-Aldrich Corporation, Mahadevapura, Bangalore, India, 2001.

2000–2001.bLancaster, 2002–2003: Research Chemicals, Lancaster Synthesis Ltd., Lancashire, England, 2003.cRef.[17]

M. A. PASHA ET AL.322

oven (LG, Little Cheff, 230 V, �50 Hz). Reactions were

monitored on TLC by comparison with authentic samples.

Melting points were taken in open capillaries using paraffin

bath and are uncorrected.[28] Yields refer to the isolated

yields of the products after purification by silica gel chromato-

graphy. The IR spectra of the products were recorded on a

Nicolet 400 D FT-IR spectrophotometer. H1 NMR spectra

were recorded on a 400 MHz Bruker instrument. The

chemical shift values (d ppm) reported are relative to TMS in

CDCl3 as solvent.

General Procedure for Conversion of AromaticCompounds to Aromatic Ketones underMicrowave Irradiation

A mixture of benzene (0.078 g, 1 mmol) and TiO2 (0.039 g,

0.5 mmol) was taken into a Pyrex cylindrical tube; benzoyl

chloride (0.140 g, 1 mmol) was added, homogenized and

irradiated in a commercial microwave oven (320 W). At the

end of irradiation (25 sec), the mixture was cooled to room

temperature and extracted with diethyl ether. The organic

layer was dried over sodium sulphate, and the solvent

was removed under vacuum. The crude product was

subjected to silica gel column chromatography using 5%

EtOAc in light petroleum ether as eluent to get benzophenone

(0.13 g).

CONCLUSION

The present microwave irradiation procedure provides an

efficient and very simple method for Friedel–Crafts acylation

of aromatic compounds using non-toxic and inexpensive

TiO2 powder. This catalytic system is expected to contribute

to the development of more benign acylation of aromatics

with acid chlorides.

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Recovery

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2 30 64 90

3 40 60 88

FRIEDEL CRAFTS ACYLATION OF AROMATIC COMPOUNDS IN SOLVENT-FREE CONDITIONS 323

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