Effects of high pressure on Friedel-Crafts benzoylation

Article abstract of DOI:10.1002/poc.854

A study of Friedel-Crafts benzoylation under high pressure is reported. Activated (toluene) to non-activated (benzene) and deactivated (fluorobenzene) aromatic substrates were acylated (benzoyl chloride) at 34°C for 3 h 50 min in the presence of the usual Lewis acid AlCl₃, raising the pressure from atmospheric pressure (1 bar) to 10 kbar. Non-activated and deactivated aromatic substrates were found to be more sensitive to the effect of the high pressure. Indeed, fluorobenzene led to the expected aromatic ketone with a 56% yield under the conditions mentioned above (5 kbar), whereas the yields constantly decreased for toluene when the pressure increased. Hyperbaric activation has the advantage of being able to conduct such a transformation on deactivated substrates, avoiding very acidic catalysts such as trifluoromethanesulfonic acid or expensive activators such as gallium nonaflate. Copyright

Full text of DOI:10.1002/poc.854

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2005; 18: 268–271
Published online 17 September 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/poc.854
Short Communication
Effects of high pressure on Friedel–Crafts benzoylation
1
1
2
1
Florence Mugnier, Anne Harrison-Marchand, * Fran c¸ oise Igersheim and Jacques Maddaluno
1
Laboratoire des Fonctions Azot e´ es et Oxyg e´ n e´ es Complexes de l’IRCOF, UMR 6014 CNRS, Universit e´ de Rouen,
7
6821 Mont Saint-Aignan C e´ dex, France
Rhodia Recherche, 85 rue des Fr e` res Perret, BP 62, 69192 Saint-Fons C e´ dex, France
2
Received 22 April 2004; revised 21 June 2004; accepted 13 July 2004
ABSTRACT: A study of Friedel–Crafts benzoylation under high pressure is reported. Activated (toluene) to non-
ꢀ
activated (benzene) and deactivated (fluorobenzene) aromatic substrates were acylated (benzoyl chloride) at 34 C for
3
h 50 min in the presence of the usual Lewis acid AlCl , raising the pressure from atmospheric pressure (1 bar) to 10
3
kbar. Non-activated and deactivated aromatic substrates were found to be more sensitive to the effect of the high
pressure. Indeed, fluorobenzene led to the expected aromatic ketone with a 56% yield under the conditions mentioned
above (5 kbar), whereas the yields constantly decreased for toluene when the pressure increased. Hyperbaric
activation has the advantage of being able to conduct such a transformation on deactivated substrates, avoiding
very acidic catalysts such as trifluoromethanesulfonic acid or expensive activators such as gallium nonaflate.
Copyright # 2004 John Wiley & Sons, Ltd.
KEYWORDS: high pressure; friedel–crafts; benzoylation, deactivated aromatic substrates; aluminum trichloride
8
related to nitration reactions at 2–3 kbar. One example of
INTRODUCTION
9
10
hydroxyalkylation and only one acylation have been
described under similar conditions. Concerning this last
Friedel–Crafts benzoylations are an important class of
reactions in organic synthesis. The access to numerous
aromatic ketones follows this synthetic route, and var-
ious efforts have been especially conducted to achieve
electrophilic benzoylations from deactivated benzenes.
10
application, reported by Coillet et al., toluene and ben-
zene were reacted with benzoyl chloride in the presence of
1
–3
ꢀ
aluminum trichloride at 29.6 C while the pressure was
raised up to 1.5 kbar. It was found that the second-order
rate constant for the benzoylation of benzene was doubled
on going from 1 bar to 1.5 kbar, a result from which a
4–6
5b,7
Thus, halobenzenes,
7
nitrobenzene
-trifluorotoluene have been functionalized using specific
and even ꢀ, ꢀ,
ꢀ
6¼
ꢁ1
reagents for acylation and/or catalysts. For instance, ben-
zoylations of fluorobenzene, chlorobenzene and dichloro-
benzene have been successfully carried out using a
catalytic amount of gallium nonafluorobutanesulfonate
negative activation volume (ÁV ¼ ꢁ11.4 ml mol ) was
calculated, suggesting that Friedel–Crafts benzoylations
could be favoured under high pressure.
As a second example, we report in this paper our
results and observations on Friedel–Crafts benzoylations
under hyperbaric activation. Activated (toluene) to non-
activated (benzene) and deactivated (fluorobenzene) aro-
matics were studied and compared.
6c
(1–5 mol%) as they afforded the corresponding aromatic
ketones in good (71%) to excellent (99%) yields. The
7
single example of acylation of ꢀ,ꢀ,ꢀ-trifluorotoluene
(nitrobenzene was also studied in this work) using methyl
benzoate as the acylating reagent with trifluoromethane-
sulfonic acid as the catalyst gave access to the correspond-
ing ketones in yields up to 80%. Unfortunately, we have
been unable to repeat these latter results. However, the
great opportunities that such a transformation offers in
terms of industrial valorization prompted us to examine
an alternative solution resorting to high pressure.
RESULTS
1
0
We first decided to work using Coillet et al.’s conditions
ꢀ
with benzoyl chloride in the presence of AlCl at 34 C
3
for 3 h 50 min. The aromatic substrate was introduced as
the solvent (molar fractions: [aromatic substrate]:[Lewis
acid þ ArCOCl] ¼ 0.94:0.06) and the pressure was raised
from 1 bar to 10 kbar. Benzene and fluorobenzene could
be acylated under these conditions (Scheme 1, Table 1)
despite the low solubility of the catalyst at atmospheric
pressure in such mixtures.
Relatively little is known about high-pressure effects on
SEAr and the few studies conducted on this topic are mostly
*Correspondence to: A. Harrison-Marchand, Laboratoire des
Fonctions Azot e´ es et Oxyg e´ n e´ es Complexes de l’IRCOF, UMR 6014
CNRS, Universit e´ de Rouen, 76821 Mont Saint-Aignan C e´ dex, France.
E-mail: anne.harrison@univ-rouen.fr
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 268–271

EFFECTS OF HIGH PRESSURE ON FRIEDEL–CRAFTS BENZOYLATION
269
Scheme 1. Benzoylation of benzene and fluorobenzene
using the aromatic substrate as the solvent
Scheme 2. Benzoylation of toluene, benzene and fluoro-
benzene under high pressure using benzoyl chloride as
solvent
The two aromatic substrates considered behave differ-
ently under hyperbaric conditions. With benzene (entries
media were obtained before and after transformation,
showing a better solubility of the catalyst.
1
–3), the yields constantly decreased with increasing
pressure, whereas with fluorobenzene (entries 4–6), the
yield doubled on going from 1 bar to 5 kbar. This differ-
ence in the pressure dependence might be the result of the
pressure-induced crystallization of the aromatic sub-
strate/solvent. Indeed, it is known that the melting-point
The yields are generally lower for benzene and fluor-
obenzene than those previously measured, suggesting
Table 2. Benzoylation of benzene, toluene and fluoroben-
ꢀ
zene in the presence of AlCl at 34 C for 3 h 50 min and
3
using benzoyl chloride as the solvent
ꢀ
ꢀ
of benzene increases from 5.5 C at 1 bar to 114 C at
5
11
a
kbar. Hence, diffusion phenomena are likely to be-
come critical with increasing pressure and, consequently,
the yields of the reactions can be seriously altered.
Entry
R
P (bar)
Yield (%)
b
34 (67 )
1
2
3
4
5
6
7
8
9
H
H
H
1
1000
5000
10 000
1
1000
5000
10 000
1
46
34 (48 )
ꢀ
Fluorobenzene, which crystallizes at ꢁ40 C at 1 bar, is
b
b
23 (43 )
probably less prone to this phenomenon. The low yields
measured as a whole can be additionally assigned to the
poor solubility of AlCl in these reaction media, noticed
H
Me
Me
Me
Me
F
F
F
F
73
59
59
41
3
when preparing the samples.
We then decided to work using the aroyl chloride as
the solvent (molar fractions: [aromatic substrate]:
b
5 (22 )
12
56 (47 )
10
11
1000
5000
10 000
b
[
Lewis acid]:[ArCOCl] ¼ 0.06:0.04:1.00) in an attempt
b
24 (48 )
1
2
to maintain comparable experimental conditions for all
the aromatic substrates considered. Toluene, benzene and
fluorobenzene were independently reacted with benzoyl
a
The other products identified are only starting materials.
Yields obtained when the aromatic substrate is used as the solvent (cf.
Table 1).
b
ꢀ
chloride in the presence of AlCl at 34 C for 3 h 50 min,
3
while the pressure was raised from 1 bar to 10 kbar
(
Scheme 2, Table 2, Fig. 1). This time, homogeneous
Table 1. Benzoylation of benzene and fluorobenzene in the
ꢀ
presence of AlCl3 at 34 C for 3 h 50 min and using the
aromatic substrate as the solvent
a
Entry
R
P (bar)
Yield (%)
1
2
3
4
5
6
H
H
H
F
F
F
1
67
48
43
22
47
48
5000
10 000
1
5000
10 000
Figure 1. Benzoylation yields of (&) benzene, (~) toluene
and (*) fluorobenzene vs pressure
a
The other products identified are only starting materials.
Copyright # 2004 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2005; 18: 268–271

2
70
F. MUGNIER ET AL.
that benzoyl chloride probably crystallizes even more
quickly than benzene under high pressure. However, this
solvent being identical and the proportions being the
same for all of the experiments conducted, the conse-
quences of this crystallization are expected to be similar
for the three aromatic substrates. It remains clear from
Fig. 1 that the effect of high pressure is still fully
dependent on the substrate. Maximum efficiency is ob-
served with fluorobenzene, the benzoylation yield of
which doubles on going from 1 bar to 1 kbar (entries 9
and 10) and increases 10-fold between 1 bar and 5 kbar
(
entries 9 and 11). At higher pressure (10 kbar, entry 12),
the activation becomes less effective, leading to lower
conversions. Hence an ‘optimum pressure’ (OP) is asso-
ciated with an optimal effect. A similar evolution is
observed with benzene (entries 1–4), the best yield being
obtained at a lower OP (1 kbar, entry 2). By contrast, for
toluene the yield constantly decreases when the pressure
increases (entries 5–8). This result suggests that the
crystallization of the aromatic substrate cannot be held
directly responsible for the yield variations since toluene,
ꢀ
the melting-point of which increases from ꢁ95.1 C at
ꢀ
Scheme 3. Suggested mechanisms of Friedel–Crafts
reactions
1 bar to 30 C at 9.6 kbar, remains probably more fluid
than benzene with increasing pressure.
Such result is in complete accordance with Coillet
et al.’s work on the nitration of toluene, benzene and
chlorobenzene between 1 bar and 2.3 kbar in acetic acid
need any activation to reach TS1 or TS2, the limiting step
of the reaction would become HCl elimination, which is
increasingly disfavored on raising the pressure.
8a
or nitromethane.
activation volumes for all the substrates considered, the
The authors reported negative
In conclusion, we have reported new examples of
Friedel–Crafts acylations conducted under high pressure.
This activation affords better results with deactivated
benzenes. Further studies should involve other deacti-
vated aromatics such as chlorobenzene, nitrobenzene and
ꢀ,ꢀ,ꢀ-trifluorotoluene. Concerning the last substrate,
aluminum trichloride will have to be replaced as
this catalyst reacts with trifluorotoluene to give
6¼
|
ÁV | values being larger for deactivated aromatics,
suggesting that the latter would indeed be more sensitive
6¼
toluene
to the effect of the pressure (in AcOH: ÁV
¼
6¼
3
ꢁ1
6
3
ꢁ1
ꢁ
10 cm mol ; ÁV
¼ ꢁ22 cm mol ; ÁV
benzene
ꢁ1
3
¼
ꢁ 23.5 cm mol ).
chlorobenzene
13
DISCUSSION
trichlorotoluene.
The details of Friedel–Crafts acylation are not completely
understood, although two mechanisms are retained to
date (Scheme 3). For this reason, it is difficult to
propose a rationale for the results described above. The
following may nevertheless be considered.
Acknowledgments
1
2
We thank Rhodia-Recherche and the CNRS for a PhD
grant to F.M.
Whatever the mechanism, the reaction between ArH
and the putative 1:1 acyl chloride–AlCl complex (me-
3
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J. Phys. Org. Chem. 2005; 18: 268–271