Chlorine borrowing: An efficient method for an easier use of alcohols as alkylation agents

Article abstract of DOI:10.1039/b807230b

Chlorine functionalised tin dioxide nanoparticles proved able to partially convert alcohols into the corresponding chlorides, which act as alkylation agents with an increased electrophilicity, as evidenced on ether formation and Friedel-Crafts reactions.

Full text of DOI:10.1039/b807230b

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www.rsc.org/greenchem | Green Chemistry
Chlorine borrowing: an efficient method for an easier use of alcohols
as alkylation agents†
Philippe Makowski,a Regina Rothe,a Arne Thomas,a Markus Niederbergerb and Fre´de´ric Goettmann*a,c
Received 29th April 2008, Accepted 4th November 2008
First published as an Advance Article on the web 14th November 2008
DOI: 10.1039/b807230b
Chlorine functionalised tin dioxide nanoparticles proved
able to partially convert alcohols into the correspond-
ing chlorides, which act as alkylation agents with an
increased electrophilicity, as evidenced on ether formation
and Friedel–Crafts reactions.
amine syntheses, new activation paths are required. In that
respect, recent progresses in understanding nonaqueous sol-
gel chemistry are a great source of inspiration.16 Indeed, this
chemistry deals with the controlled synthesis of metal oxides
under water free conditions and rely on the organic chemistry of
alcohols, carboxylic acids or ketones as an oxygen source. The
reactions providing the needed oxygen were mainly found to be
based on the formation of alkyl chlorides, esters, ethers or C–C
coupling products and were recently reviewed.17 Our attention
was attracted by the fact that during the nonaqueous synthesis
of SnO2 nanoparticles (SnO2NPs), starting with SnCl4, in benzyl
alcohol as a solvent, almost all the alcohol was converted into
the corresponding ether.18 This pointed to a possible catalytic
activity of these particles, which will be investigated herein.
The employed SnO2 nanoparticles were synthesised as previ-
ously described, by heating SnCl4 in benzyl alcohol at 100 ◦C for
24 h.18 The resulting particles are crystalline and feature a mean
size of about 4 nm as described in the initial publication.† For
reference experiments, chlorine free SnO2 nanoparticles were
In the first issue of this Journal, J. H. Clark exposed his
vision of green chemistry in the article “Green chemistry:
challenges and opportunities”.1 Therein, he selected Friedel–
Crafts acylations as an archetypical example of industrially
relevant, but immensely wasteful reactions. Indeed, the use of
both an acyl chloride as electrophile and a homogeneous Lewis
acid as promoter resulted in large amounts of, partly harmful,
waste products. The same considerations are true for Friedel–
Crafts alkylations. Nevertheless, due to their importance in
synthetic chemistry, a lot of work has been devoted to finding
true heterogenous catalysts for these reactions, such as zeolites,
polyoxometalates or mesoporous oxides.2–6 Another goal of
these works was to enable the use of electrophiles greener than
halogenoalkanes. In that respect, alcohols, which have already
been largely used as alkylating agents for ketones, malonates
or nitriles,7–10 were thought to be ideal candidates. Indeed, they
are easily accessible from biomass or hydroformylation products
and produce only water as a by product. Many successes were
recorded in the use of alcohols for Friedel–Crafts alkylations.
Yadav et al., for example, reported on the use of super acids
to alkylate functional aromatics with alcohols.11,12 Alternatively,
Roy and co-workers described the use of a bifunctionnal Ir-
Sn catalyst for this reaction. In this approach the tin centre
was reported to act as a Lewis acid to activate the alcohol,
while the iridium centre activated the electrophile.13,14 The use of
mesoporous carbon nitride as a catalyst for such reactions was
also recently described.15 Most of these approaches, however,
suffered either from a lack of versatility or too harsh reaction
conditions.
also synthesised by using tin tert-butoxide as a precursor.†19
A
preliminary test to convert benzyl alcohol (300 mg) in dibenzyl
ether in the presence of a catalytic amount of SnO2NPs (25 mg)
under mild conditions (100 ◦C for 20 h), indeed showed the
formation of ether but also of a small amount of benzyl
chloride.† The needed chlorine atoms had to be provided by
the nanoparticle itself, as it was previously evidenced that
these SnO2NPs were decorated with chloride ligands.18 We thus
assumed that the formed chloro-alkanes were not only by-
products of the reaction, but also acted as intermediates in the
formation of the ether, as depicted in Scheme 1. Interestingly,
the exchange of halogeno- and hydroxy-moieties between metal
halides and alcohols to yield the corresponding metal oxide and
halogeno-alkanes has early been identified as a major process in
non-hydrolytic sol-gel chemistry.20
In order to allow for a more general use of alcohols as
alkylating agents for, for example, Friedel–Crafts reactions
or other C–C bond forming reactions, but also for ether or
aMax-Planck Institute of Colloids and Interfaces, Scientific Campus
Golm, 14476, Potsdam, Germany
Scheme 1 Proposed mechanism for the SnO2NPs catalysed condensa-
tion of benzyl alcohol.
bDepartment of Materials, ETH Zu¨rich, Wolfgang-Pauli-Str. 10, 8093,
Zu¨rich, Switzerland; Fax: +41 44 632 11 01; Tel: +41 44 633 63 90
cInstitut de Chimie Se´parative de Marcoule, UMR 5257, Site de
Marcoule, BP 17171, 30207, Bagnols sur Ce`ze, France.
E-mail: frederic.goettmann@cea.fr; Fax: (+33) 466 797 611;
Tel: (+33) 466 905 758
† Electronic supplementary information (ESI) available: Synthetic pro-
cedure for the used nanoparticles. See DOI: 10.1039/b807230b
These observations are of great synthetic importance. Indeed,
as halogenoalkanes are much better electrophiles than alcohols
they open the possibility of a generalised use of alcohols as
alkylating agent via a kind of chlorine borrowing mechanism, as
depicted in Scheme 2.
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atomic emission spectroscopy (ICP-AES) was used to quantify
the tin content and ion chromatography to quantify the chlorine
in solutions resulting from the dissolution of SnO2NPs in
nitric acid. This enabled us to evaluate that 25 mg of catalyst
corresponded to 0.14 mmol of tin and 0.06 mmol of chlorine.
As a consequence, the turnover number (TON, determined as the
number of mol of substrate converted at the end of the reaction
per mol of catalyst) in the case of benzyl acohol (Table 1, entry 1)
would be 20 calculated on the basis of tin and 46 calculated on
the basis of chlorine. These are relatively modest TONs but they,
at least, evidence that the process is really catalytic.
A series of tests was done on benzyl alcohol, in order to test the
recyclability of our catalyst. For this purpose, the nanoparticles
were separated by centrifugation after each reaction and reused
with new batches of fresh benzyl alcohol at 150 ◦C for 80 h.
As can be seen in Fig. 1, the first recyclings proved effective
even if moderate activity and selectivity losses are observed.
This indicates that the surface of our catalyst is still covered
with active chlorinated sites after a few recyclings. The fourth
test however evidenced strong activity and selectivity losses.
The composition of the resulting reaction mixture could not be
completely analysed, but GC-MS analysis showed the formation
of benzaldehyde, benzoic acid benzyl ester and some higher mass
compounds.
Scheme 2 Proposed mechanism for a general SnO2NPs catalysed
enhancement of the electrophilicity of alcohols.
In order to test this hypothesis, we attempted to catalyse
the conversion of alcohols into ethers and their further use
in Friedel–Crafts alkylations with SnO2NPs. In a first set of
experiments pure alcohols or mixtures of alcohols were heated
between 120 and 150 ◦C with an oil bath in screw capped
glass tubes in the presence of SnO2NPs. During the reaction,
a liquid condensed on the upper cool glass tube surface, which
was attributed to water formation. Due to the temperature of
the reaction mixtures, no formation of a second phase was
observed. Table 1 displays some of the results we obtained. As
can be seen, the wanted ethers were obtained in good yields
with high selectivities as soon as benzyl alcohol derivatives
were used (Table 1, entries 1, 3, 4), while other alcohols
proved to be more difficult to convert. However, this result is
particularly advantageous for the preparation of dissymmetric
ethers, as evidenced by the condensation of benzyl alcohol
with hexanol and cyclohexanol. These results are consistent
with those recently obtained by Corma and Renz with tin
supported on micro- and mesoporous oxides, although we had
to employ harsher reaction conditions.21 But it is, to the best
of our knowledge, the first time a system containing mainly tin
oxide is used for this purpose. Interestingly, particles prepared
using Sn(tBuO)4 as a tin source did not exhibit the same catalytic
activity (Table 1, entry 2), thus supporting our assumption that
chlorine was playing a major role in this reaction.
Fig. 1 Recycling of the SnO2NPs. The test reaction was the conversion
of benzyl alcohol into dibenzylether, at 150 ◦C for 80 h. The conversion
was determined by GC-MS as the benzyl alcohol consumption. The
selectivity is expressed as the ratio between formed dibenzyl ether and
the benzyl alcohol consumption.
In order to be able to determine an accurate turnover
number, we further investigated the chemical composition of
the employed SnO2 nanoparticles. Inductively coupled plasma-
Table 1 SnO2NPs catalysed etherification of various alcoholsa
Entry
Substratea
Temp./◦C
Time/h
Conv. (%)b
Productsc
1
2
3
4
5
6
7
Benzyl alcohol
Benzyl alcohold
4-Methylbenzyl alcohol
4-Chlorobenzyl alcohol
Hexanol
150
150
120
130
150
120
150
80
80
48
100
1
44
64
3
2
11
Dibenzyl ether 95%
Dibenzyl ether 100%
Di(4-methyl)benzyl ether 100%
Di(4-chloro)benzyl ether 100%
Dihexyl ether 100%
Dicyclohexylether 100%
Dibenzyl ether 10%
Hexyl benzyl ether 90%
Dibenzyl ether 10%
Cyclohexyl benzyl ether 90%
20
120
120
96
Cyclohexanol
Benzyl alcohol
Hexanole
8
Benzyl alcohol
Cyclohexanole
150
96
20
a In a typical procedure 300 mg of the pure alcohol were heated in presence of 25 mg of NPs. b Conversion rates determined by GC on the basis of
the initial substrate amount. c The indicated percentages correspond to the amount of the corresponding product relative to the overall amount of
formed products. d Reference test with chlorine free nanoparticles. e For these tests 200 mg of benzyl alcohol were heated in 2 g of the other alcohol
as a solvent with 25 mg of particles.
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Table 2 SnO2NPs catalysed Friedel–Crafts alkylation of various aromatic compounds with alcoholsa
Aromatic compound
Electrophile
Benzene
Toluene
Anisole
Entry
Yield (%)b
Yield (%)
p/oc
Yield (%)
p/o
1
2
3
4
5
6
7
Benzyl alcohol
Benzyl alcohold
Benzyl alcohole
4-Methylbenzyl alcohol
Cinnamyl alcohol
Isopropanol
93
0
n.a.
90
100
0
100
0
n.a.
100
100
5
0.9:1
—
—
0.5:1
1:0.55
1:1
97
0
50
100
100
9
1:1
—
1:1
1.4:1
1:0.26
0.7:1
1:1
Cyclohexanol
0
0
—
10
a In a typical reaction 25 mg of catalyst, 100 mg of alcohol and 5 ml of aromatic compound were heated to 150 ◦C for 120 h. b The yields were
determined by GC-FID with mesitylene as a reference and correspond to the molar ratio between the obtained alkylation product and the initial
amount of alcohol. c p/o corresponds to the molar ratio between para and ortho substituted alkylation products. d Reference test with chlorine free
SnO2NPs. e Reference test with chlorine free SnO2NPs but in presence of 20 mg of benzyl chloride, this test was only undertaken with anisole.
In a second study, we investigated whether the intermediate
chloride species could also act as electrophiles for Friedel–
Crafts reactions, as depicted in Scheme 3. Even if pure tin
oxide does not seem to be a common catalyst for Friedel–Crafts
reactions, the fact that tin complexes proved Lewis acidic enough
to promote such reactions22 encouraged us to proceed to our
tests without an additional Friedel–Crafts catalyst. In a typical
catalytic experiment 25 mg of catalyst, 100 mg of alcohol and
5 ml of aromatic compound were heated to 150 ◦C in 23 ml acid
digestion bombs (Parr Instrument) for 120 h. Table 2 displays
some of the obtained results.
As compared to other approaches to use alcohols as an alkylat-
ing agent, the reaction conditions we had to employ remained
harsh, but we are confident in that this inconvenience can be
overcome. Indeed, tin dioxide is not known to be a good Friedel–
Crafts catalyst and we think that our results can be enhanced
by designing bifunctional systems featuring both chlorinated tin
sites and stronger Lewis acidic sites. In addition, the possibility
of avoiding the use of noble metals13,14 can possibly balance the
requirement of harsher reaction conditions. Moreover, we are
convinced that this mechanism could be much more general
and allow alcohols to react more easily with a large variety of
nucleophiles, such as ketones, nitriles or amines.
The Max-Planck Society is gratefully acknowledged for
financial support within the framework of the enerchem project
house, so is also the CEA (French Atomic Energy Commission).
The authors also thank Agne`s Grandjean, Ve´ronique Dubois
and Didier Maurel for the chemical analysis of the SnO2NPs.
Scheme 3 Proposed mechanism for the SnO2NPs catalysed benzylation
of bezene with benzyl alcohol.
Notes and references
Here again, the Friedel–Crafts alkylation products are ob-
tained in high yields as long as very active alcohols are used
(Table 2, entries 1, 4, 5). This observation is consistent with
other reports on the use of benzyl alcohol derivatives.23–25 In the
case of the reaction of benzyl alcohol with benzene the TON
was calculated to be 6 on the basis of tin and 14 on the basis of
chlorine. It is also worth noticing here, that, contrary to previous
studies, the use of an electron rich aromatic derivative is not
required. Indeed, benzene reacts nearly as well as toluene or
anisole with active alcohols. In addition, toluene and anisole
also give small amounts of alkylation products with less active
secondary alcohols, which seems to be a novelty in the field.
As for the ether formation reaction, chlorine free SnO2NPs
show no catalytic activity. On the contrary the same SnO2NPs
yielded the desired benzyl alcohol alkylation product on anisole
when 20 mg of benzyl chloride were added to the reaction
mixture (Table 2, entry 3). Interestingly, the amount of obtained
alkylation product is three time higher than the amount of
added benzyl chloride, which clearly proves that chlorine
transfer is possible and further supports our chlorine borrowing
mechanism.
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