BiCl3-catalyzed Friedel-Crafts acylation reactions: Bismuth(III) oxychloride as a water insensitive and recyclable procatalyst

Article abstract of DOI:10.1016/S0040-4039(03)00215-6

The Friedel-Crafts acylation of activated and polycyclic aromatics is efficiently catalyzed by bismuth(III) chloride which is generated in situ from bismuth(III) oxychloride, a water insensitive and eco-friendly material. Bismuth(III) oxychloride is easily recovered in near quantitative yields after an aqueous work-up.

Full text of DOI:10.1016/S0040-4039(03)00215-6

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 2037–2040
BiCl3-catalyzed Friedel–Crafts acylation reactions:
bismuth(III) oxychloride as a water insensitive and
recyclable procatalyst
Sigrid Re´pichet,a Christophe Le Roux,a,* Nicolas Roquesb and Jacques Dubaca
aHe´te´rochimie Fondamentale et Applique´e, Universite´ Paul-Sabatier, 118 route de Narbonne, 31062 Toulouse Cedex 04, France
bRhodia Organique Fine, Centre de Recherche de Lyon, 85 avenue des Fre`res Perret, 69192 Saint-Fons Cedex, France
Received 19 November 2002; accepted 20 January 2003
Abstract—The Friedel–Crafts acylation of activated and polycyclic aromatics is efficiently catalyzed by bismuth(III) chloride
which is generated in situ from bismuth(III) oxychloride, a water insensitive and eco-friendly material. Bismuth(III) oxychloride
is easily recovered in near quantitative yields after an aqueous work-up. © 2003 Elsevier Science Ltd. All rights reserved.
The applications of organobismuth(V)1 and, more
recently, of bismuth(III)2 compounds in organic reac-
tions are well known. Among the latter, the use of
Bi(III) derivatives in catalytic transformations appears
to be versatile and promising in their large-scale devel-
opment. Bismuth compounds are attractive since many
of them are commercially available, at a low cost, and
have little or no toxicity.3
Bismuth(III) chloride (1) is the Bi-derivative for which
the Lewis acid activity has been the most studied,2 but
it is moisture sensitive and non-recoverable from
aqueous solutions. On the contrary, bismuth(III) oxy-
chloride (2) is a water insensitive material which, in
addition, exhibits an extremely low toxicity (LD50 ORL
(rat): 22 g/kg), as a result of its almost complete
insolubility in aqueous solutions such as biological
fluids.3 Moreover, its transformation into BiCl3 is possi-
ble.10 Thus BiOCl could be regarded as a procatalyst
for reactions involving BiCl3 as catalyst, and/or allow-
ing the recovery of the Bi-based catalyst after
hydrolytic work-up. We investigate here some Friedel–
Crafts acylation reactions with activated and polycyclic
aromatics (Eq. (1)) in the presence of 1 or 2, and the
possibility of recovery and recycling the Bi-based
catalyst.
Bi(III) derivatives are mainly involved: (i) in oxido–
reduction reactions;4 (ii) in Lewis acid activated reac-
tions,2 due to the availability of valence shell
unoccupied orbitals (or BiꢀX s*);5 (iii) in ligand
exchange reactions which, if they are reversible, take
place in the catalytic cycle;2f and by a characteristic
property, the softness of bismuth compared with the
hardness of small size electronegative elements,6 leading
to labile acid–base interactions. This avoids the trap-
ping of the Bi-based catalyst by O- or N-containing
products (self-blocking reactions), for example in
Mukaiyama-aldol, Michael,7 carbonyl- and aza-Diels–
Alder reactions,8 or Friedel–Crafts acylation and
sulfonylation.2f
(1)
In the case of aromatic ethers, strongly activated sub-
strates, BiCl3 (1) was able to catalyze their acylation
efficiently at about 80–85°C, using an acid chloride as
reagent, and at higher temperatures (140°C), using an
acid anhydride.11 Many Lewis acids are efficient for
such a reaction.9 In the case of toluene 3, the aromatic
ring is much less activated than in anisole (s+ (Me)=
Among these reactions, the FC acylation and related
reactions require classically at least stoichiometric
quantities of strong oxophilic Lewis acids, such as
metal chlorides (AlCl3, TiCl4, FeCl3),9 which are non-
recoverable materials after aqueous work-up. Conse-
quently, the large scale development of these processes
leads to corrosion and environmental problems due to
large amounts of acidic effluents and solid wastes.
−0.31, (s+ (OMe)=−0.78),12 and its acylation pis more
p
difficult to achieve. Numerous metal chlorides,9 and
even some metal triflates,13a,b are inefficient in the cata-
lytic acylation of toluene, while some other catalytic
* Corresponding author. Fax: +33-5-6155-8204; e-mail: leroux@
chimie.ups-tlse.fr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)00215-6

2038
S. Re´pichet et al. / Tetrahedron Letters 44 (2003) 2037–2040
systems containing triflic acid13c,d or the potentially
explosive lithium perchlorate,13e,f have been reported
for such reaction. The catalytic activity of 1 for the
acetylation of 3 was previously reported as very low.14
However, we examined the benzoylation of 3, and we
observed that the activity of 1, which is both triflate-
and perchlorate-free, is rather remarkable: an isolated
yield of 40–70% of methylbenzophenone (10) was
obtained using 10–20 mol% of 1, after 5 h of heating at
reflux (Table 1, entries 1 and 2). The benzoylation yield
became high with xylenes (4a–c) (entries 3, 4, 6), and
specially with mesitylene (5) (entries 9 and 10).
ery of ‘bismuth’ from the crude 1-catalyzed acylation
reaction, after aqueous work-up, simply required the
neutralization of the aqueous layer with NaOH. This
method allows for quantitative precipitation of BiOCl
(2).
Typical procedure for the benzoylation of mesitylene (5).
A 100 mL flask equipped with a condenser and a
stirring bar was charged with mesitylene (5) (12 g; 0.10
mol), benzoyl chloride (7.03 g; 0.05 mol) and bismuth
chloride (1) (1.58 g; 5 mmol). The flask was heated in a
thermostated oil bath at 120°C for 4 h. After cooling,
GC analysis of crude product using tetradecane as
internal standard indicated that 2,4,6-trimethylben-
zophenone (16) had been formed in quantitative yield
(with respect to benzoyl chloride). Dichloromethane (80
mL) and 6% aqueous HCl (80 mL) were added to the
red–brown crude mixture. The acidic layer was sub-
jected to another extraction with dichloromethane (80
mL). The combined organic phases were dried over
sodium sulfate and concentrated under reduced pres-
sure. The product was purified by flash chromatogra-
phy (silica gel; eluent: pentane/dichloromethane=1:1)
to give 10.10 g (90% yield) of ketone 16 [954-16-5],
identified from an authentic sample.18 1H NMR
(CDCl3): l 2.10 (s, 6 H, 2- and 6-Me), 2.34 (s, 3 H,
4-Me), 6.91 (s, 2 H, aromatic protons of mesityl group);
other aromatic protons: 7.44 (m, 2 H), 7.57 (m, 1 H)
and 7.82 (m, 2 H). GC–MS, m/z %: 224 (M+, 88), 223
(96), 209 (42), 208 (38), 147 (57), 119 (36), 105 (27), 91
(48), 77 (100), 51 (51).
Polycyclic aromatics are sensitive to strong Lewis acids
(AlCl3, FeCl3, TiCl4) commonly used for their
acylation, and this reaction is not regioselective.9a,15,16
A milder activator has been described, but it requires a
large excess of the (RCO)2O/Me2S/BF3 system and
strictly anhydrous conditions.16 Interestingly,
1
appeared as an efficient catalyst for the benzoylation of
three polycyclic aromatics, naphthalene (6), anthracene
(7) and pyrene (8), and the reactions were regioselective
(Table 1, entries 11–13).
The recovery and the recycling of a FC acylation
catalyst is seldom possible after aqueous work-up.
However, the recovery of some metal triflates (rare
earths, Bi) has been reported.13a,b,f Another alternative
consists in the use of supported catalysts, which avoids
or strongly reduces the effect of leaching.17 Since 1 is
freely soluble in an HCl-containing solution, the recov-
Table 1. Bismuth(III) chloride (1)-catalyzed or bismuth(III) oxychloride (2)-procatalyzed acylation of aromatics
Entry
ArH
Acylating reagent (ArH/RCOCl/1)a,b
Conditionsc
Productd and yield (%)e
1
2
3
4
5
6
7
8
Toluene (3)
Toluene (3)
PhCOCl (2:1:0.1)
PhCOCl (2:1:0.2)
PhCOCl (2:1:0.1)
Me(CH2)4COCl (30:1:0.1)
PhCOCl (2:1:0.1)
120°C; 5 h
120°C; 5 h
120°C; 12 h
100°C; 24 h
120°C; 5 h
120°C; 12 h
70°C; 8 h
10f; 40
10f; 70
11a; 93
12; 88
11b; 80
11c; 90
13; 89
14; trace, 15; 62
16; 90
17; 97
18; 80
19; 84
20; 72
21; 71
22; 94
23; 96
o-Xylene (4a)
m-Xylene (4b)
m-Xylene (4b)
p-Xylene (4c)
Mesitylene (5)
Mesitylene (5)
Mesitylene (5)
Mesitylene (5)
Naphthalene (6)
Anthracene (7)
Pyrene (8)
PhCOCl (2:1:0.1)
MeCOCl (2:1:0.1)
Me2CHCOCl (2:1:0.1)
PhCOCl (2:1:0.1)
p-NO2C6H4COCl (2:1:0.05)
PhCOClg (1:1:0.2)
PhCOClg (1:1:0.2)
PhCOClg (1:1:0.2)
Me2CHCOCl (2:1:0.1)
Me3CCOCl (2:1:0.1)
PhCOCl (2:1:0.1)
80°C; 2 h
9
120°C; 4 h
120°C; 4 h
120°C; 5 h
110°C; 2 h
110°C; 5 h
80°C; 2 h
10
11
12
13
14
15
16
Anisole (9)
Anisole (9)
Anisole (9)
100°C; 3 h
110°C; 6 h
a Molar ratios.
b For RCOCl/1=1/0.1 (resp. 1/0.2) the equivalent reaction has been carried out using RCOCl/2=1.2/0.1 (resp. 1.4/0.2) and gave identical result
under similar conditions since the reaction of 2 with acyl chlorides (Eq. (2)) occurs quasi-spontaneously (entries 2, 4, 5, 9, 11–16).
c Temperature of the oil bath.
d Acylation product and major isomer (]95%): methylbenzophenone (10), 3,4-(11a), 2,4-(11b), 2,5-dimethylbenzophenone (11c), 2,4-dimethyl-
caprophenone (12), 2,4,6-trimethylacetophenone (13), 2,4,6-trimethylisobutyrophenone (14), 2-methyl-1-mesityl-1-chloropropene (15), 2,4,6-
trimethylbenzophenone (16), 2,4,6-trimethyl-p-nitrobenzophenone (17), 1-benzoylnaphthalene (18), 9-benzoylanthracene (19), 1-benzoylpyrene
(20), p-methoxyisobutyrophenone (21), p-pivalophenone (22), p-benzophenone (23).
e Isolated yield after work-up, with respect to the minor reagent.
f o-10/m-10/p-10=18/2/80.
g Reactions carried out in chlorobenzene as solvent.

S. Re´pichet et al. / Tetrahedron Letters 44 (2003) 2037–2040
2039
of ketone 12 was similar to that obtained, in the same
experimental conditions, with antimony(III) triflate as
catalyst.23 However, the use of acetyl, pivaloyl or hex-
anoyl reagents and 3 or 4a,c, 6–8 led only to a tarry
mixture of products.
Dichloromethane was substituted by a more eco-
friendly solvent, methyl tert-butyl ether (MTBE), with-
out notable change of yield.
The aqueous solution was neutralized by cautious addi-
tion of aqueous NaOH (2 M). The solid formed was
filtered off, and washed with 20 mL of distilled water,
20 mL of acetone (or ethanol) and oven-dried at 100°C
for 5 h. This product was identified as BiOCl (2) using
an X-ray powder pattern technique.19 Mass obtained:
1.30 g (99.7% recovery of bismuth).
As regards mechanistic considerations, we have already
shown that 1 acts as a Lewis acid with activation of the
acylating reagent by initial formation, from rt, of a
coordination complex.11 In the presence of an acid
chloride, this complex is much more stable than the
complex between 1 and a ketone, which explains the
effective catalytic power of 1 in the FC acylation and
related reactions.2f However, the complex between 1
and RCOCl is not electrophilic enough to achieve the
acylation of benzene or deactivated chlorobenzene. For
that another Bi-based catalyst (or procatalyst), bis-
muth(III) triflate, must be used.2f,13b,24 Therefore,
chlorobenzenes, such as o-dichlorobenzene, can be used
as solvents for 1-catalyzed FC acylation reactions, spe-
cially for those involving solid aromatics (Table 1,
entries 11–13). In other cases, working with liquid
aromatics, solvent-free reactions are the most gen-
eral.2f,9,13b,24,25 These conditions have been used here
with the liquid aromatics 3–5 and 9, using an excess of
the aromatic substrate, necessary in the case of forma-
tion of a solid aryl ketone.
The Bi-catalyzed FC acylation would become particu-
larly interesting if 2 could be reused. The transforma-
tion of 2 to 1 is easy, and can be achieved with various
chlorinating agents,10a in particular with an acid chlo-
ride (Eq. (2)).10b Generally, it is carried out prior to the
reaction of interest, but for the acylation reactions it
can be realized in situ, using an excess of acid chloride.
(2)
With this end in view, we carried out the acylation of
aromatics 3–8 using 2 as procatalyst or 1. In both cases,
the results were similar and are collected in Table 1
(entries 2, 4, 5, 9, 11–13). In the same way, the
acylation of anisole (9) with Me2CHCOCl, Me3CCOCl
and PhCOCl, in the presence of 2 (10% mol), gave the
p-methoxyisobutyrophenone (21), -pivalophenone (22)
and -benzophenone (23) in 71, 94 and 96% yields
(entries 14–16), respectively.
In conclusion, from BiCl3 (1)-catalyzed FC acylation
reactions, bismuth was recovered in near quantitative
yields after an aqueous work-up, as BiOCl (2), a non-
toxic and moisture insensitive material. Moreover, 2
was recycled by in situ transformation into 1 using the
acylating agent, acid chloride, or before the acylation
reaction using thionyl chloride. This recovery method
of 1, through the medium of 2, seems applicable to
most of the known 1-catalyzed organic reactions.
In this last method, there is loss of a part of the acid
chloride introduced. In the case of a rare and costly
acid chloride, this disadvantage can be removed using
another chlorinating agent, for example thionyl chlo-
ride (according to the BiCl3 purification process previ-
ously reported),20 to carry out the transformation of 2
to 1 prior to the acylation reaction. Moreover, since the
reaction of 2 with the acid chloride leads to anhydride
formation, it is possible that the latter intervenes as
acylating agent, in addition to the acid chloride. In fact,
in the presence of 1 and under the temperature condi-
tions used (70–120°C), the reactivity of activated aro-
matics with respect to an acid anhydride is low
(anisole),11 or non-existent: 3 or 4b/(PhCO)2O/1=2/1/
0.1, 120°C, 5 h, no reaction. This observation is consis-
tent with the acid chloride, rather than the anhydride,
being the actual acylating agent.
In spite of the limited catalytic power of 1, this method
is a simple, cheap, safe and eco-friendly alternative to
the classical processes of the FC acylation and related
reactions.
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