Exceptionally simple catalytic system for the carbonylation of benzyl halides

Article abstract of DOI:10.1016/j.mencom.2009.09.007

A ligand-less catalytic system, Pd(OAc)₂ immobilized in NBu₄Hal melt is suggested for the synthesis of arylacetic acids by the carbonylation of benzyl bromides.

Full text of DOI:10.1016/j.mencom.2009.09.007

Mendeleev
Communications
Mendeleev Commun., 2009, 19, 256–257
Exceptionally simple catalytic system
for the carbonylation of benzyl halides
Albert L. Lapidus,a Oleg L. Eliseev,*a Tatyana N. Bondarenko,a
Nguen H. Chaub and Ruslan V. Kazantseva
a N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5303; e-mail: oleg@ioc.ac.ru
b Department of Technology, I. M. Gubkin Russian State University of Oil and Gas, 119991 Moscow, Russian
Federation
DOI: 10.1016/j.mencom.2009.09.007
A ligand-less catalytic system, Pd(OAc)2 immobilized in NBu4Hal melt is suggested for the synthesis of arylacetic acids by the
carbonylation of benzyl bromides.
Arylacetic acids and their derivatives have received attention
because they are versatile intermediates in the synthesis of a
vast range of pharmaceuticals, cosmetics and fragrances.1 The
transition metal-catalyzed carbonylation of benzyl halides is
common and direct route to arylacetic acids and their esters.
This reaction was intensively studied in past in common solvents,
as well as water-organic solvent biphasic media.2 Nowadays
low melting point organic salts (ionic liquids) are widely explored
as non-volatile, non-flammable and tunable substitutes of common
solvents in chemistry and catalysis.3 In particular, some benzyl
chloride derivatives have been carbonylated recently in [bmim]PF6
medium in the presence of 1–2% PdCl2(PPh3)2 and NaOH
water solution.4
In our recent works, efficient and recyclable catalytic systems
Pd/NBu4X/acid (X = Cl, Br; acid = TsOH, HBr) have been
proposed for the hydrocarboxylation of styrene,5,6 aliphatic
olefins7 and alcohols.6,8 Importantly, a phosphine-free palladium
catalyst immobilized in Br–-containing molten salts was found
to be more active in hydrocarboxylation than traditional Pd
phosphine complexes.6–9 We tested similar systems in hydroxy-
carbonylation of benzyl halides and discovered, quite surprisingly,
that the reaction proceeds smoothly in the absence of phosphine
ligand, as well as base.
Table 1 Hydrocarbonylation of benzyl chloride in molten salt media.
Conditions: 4 mmol of substrate, 8 μmol of Pd(OAc)2, 8 mmol of H2O,
molten salt. T = 110 °C, 2 h.
Yield, GLC (%)
Pressure/
Run
Medium/g
MPa
PhCH2COOH
PhMe
1
2a
3
NBu4Br, 2
NBu4Br, 2
NBu4Br, 2
NBu4Br, 2
NBu4Br, 2
NBu4Br, 2
NBu4Br, 2
NBu4Cl, 2
NBu4Cl, 2
NBu4Cl, 1
NBu4Cl, 0.5
NBu4Cl, 0.25
NBu4I, 2
5.0
5.0
2.5
1.0
0.5
0.5
0.5
5.0
0.5
5.0
5.0
5.0
0.5
5.0
5.0
5.0
5.0
95.4
93.2
92.5
86.4
54.2
12.4
49.2
96.6
80.7
93.3
86.4
51.0
8.2
3.0
2.0
4.0
7.5
12.8
0
6.5
0
0
4
5
6b
7c
8
9
10
11
12
13
14
15
16
17
0
0.3
0.3
2.0
0
5.0
0
[bmim]Cl, 2
[bmim]Br, 2
[bmim]PF6, 2
[bmim]BF4, 2
66.2
48.1
0
0.1
1.2
a0.1 equiv. TsOH was added. b1.5 equiv. NBu3 was added. cPdCl2(PPh3)2 as
a precursor.
to perform the reaction. Moreover, PdCl2(PPh3)2 seemed to be
less active than Pd(OAc)2 (run 7). Reaction proceeds smoothly
in the absence of stoichiometric amount of base, unlike usual
protocol for halides carbonylation.2 What is more, slight acidifying
reaction mixture leads to only a little decrease in the yield (run 2),
while adding 1.5 equiv. of NBu3 makes a strong negative impact
on carbonylation (run 6). The efficiency of various molten salts
and ionic liquids as a reaction medium is as follows: NBu4Cl >
> NBu4Br > NBu4I > [bmim]Cl > [bmim]Br >> [bmim]PF6 »
» [bmim]BF4. The best results were obtained with NBu4Cl as a
reaction medium. Phenylacetic acid yield reached 97% at 5 MPa
(run 8) and 81% at 0.5 MPa (run 9).
As far as tetrabutylammonium halides are rather expensive
materials, we tried to diminish their amount in catalytic run
as low as possible. Pretty good results were obtained at an
NBu4Cl/substrate molar ratio of 0.88–1.75: phenylacetic acid
yield was 93–97%, no toluene was formed (runs 8, 10). However,
further decrease in NBu4Cl/substrate ratio lead to lower yield
of the acid (runs 11, 12). Possible explanation of this finding is
increased dilution of NBu4Cl by water, amount of which was
constant in all the runs. Apparently, diluted NBu4Cl cannot
Benzyl chloride can be converted into benzylacetic acid in
molten salt media in the presence of Pd(OAc)2 as a catalyst
precursor with good or excellent yields (Table 1). An amount
of toluene, the product of PhCH2Cl reduction, was formed in
some runs. No phosphines or other special ligands are needed
Pd(OAc)2/NBu4X'
ArCH2X + CO + H2O
ArCH2COOH
– HX
X, X' = Cl, Br
Ar
X
Yield (%)
Ph
Ph
Cl
Br
Br
Cl
Cl
Cl
Cl
Cl
Cl
91
69
84
96
85
84
90
85
92
4-ButC6H4
2-ClC6H4
3-ClC6H4
4-ClC6H4
3,4-Cl2C6H3
3,4-(CN)2C6H3
α-C10H7
Scheme 1 Reagents and conditions: 4 mmol of substrate, 8 μmol of
Pd(OAc)2, 8 mmol of H2O, 1 g of NBu4Cl. P = 5 MPa, T = 110 °C, 4 h.
– 256 –
© 2009 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2009, 19, 256–257
solvate palladium effectively enough. Thus, catalyst activity
carbonylation while 4-tert-butylbenzyl bromide reacted more
selectively giving only 2% 4-tert-butyltoluene. Quite pure aryl-
acetic acids were obtained via correspondent Na salts by treating
diethyl ether solution of raw acid with aqueous NaOH, sepa-
rating water layer, acidifying with HCl and extracting benzylic
acid with diethyl ether.
As a result, simple base-free and phosphine-free catalytic
systems for benzyl halides carbonylation have been elaborated.
Application of tetrabutylammonium halide melts as reaction
media allows one (a) to avoid formation of stoichiometric amounts
of halide salt as a co-product and (b) to exclude expensive, toxic
and readily degradable phosphines from the catalyst formula.
decreases when water/NBu4Cl molar ratio is 4.4 or higher.
Carbon monoxide pressure is essential limiting factor of the
reaction. It seems that poor solubility of CO in ionic melt3(e)
slows CO addition to Pd catalytic complex down. However,
pressure effect is lower for NBu4Cl (entries 8, 9) than for
NBu4Br (entries 1, 3–5). Carbonylation of benzyl chloride and
its reduction into toluene seems to be competing reactions.
Upon pressure decrease, carbonylation was suppressed while
toluene formation increased (entries 1, 3–5).
Conceivable route for toluene formation is water gas shift
reaction followed by catalytic hydrogenation over Pd black
formed in some runs:
References
CO + H2O
CO2 + H2,
PhMe + HCl.
1
(a) T. Y. Shen, Angew. Chem., Int. Ed. Engl., 1972, 11, 460; (b) D. Lednicer
and L. A. Mitscher, The Organic Chemistry of Drug Synthesis, John
Wiley, New York, 1980, vol. 2, p. 62; (c) B. Liegault, J.-L. Renaud and
C. Bruneau, Chem. Soc. Rev., 2008, 37, 290; (d) W. R. Hudgins,
S. Shack, C. E. Myers and D. Samid, Biochem. Pharmacol., 1995, 50,
1273; (e) L. E. Harrison, D. C. Wojciechowicz, M. F. Brennan and
P. B. Patuy, Surgery, 1998, 124, 541; (f) S. White, D. R. Berry and
B. McNeil, Biotechnology, 1999, 75, 173; (g) S. D. Jonson and J. Welch,
Nucl. Med. Biol., 2002, 29, 211; (h) L. Sobotkova, J. Grafkova and
P. Kyslik, Enzyme Microb. Technol., 2002, 31, 992.
(a) H. Alper, K. Hashem and J. Heveling, Organometallics, 1982, 1, 775;
(b) H. Alper, N. Hamel, D. J. H. Smith and J. B. Woell, Tetrahedron Lett.,
1985, 26, 2273; (c) L. Cassar, Chim. Ind., 1985, 67, 256; (d) M. Beller,
B. Cornils, C.-D. Frohning and C. W. Kohlpaintner, J. Mol. Catal. A:
Chem., 1995, 104, 17; (e) C. W. Kohlpaintner and M. Beller, J. Mol.
Catal. A: Chem., 1997, 116, 259.
(a) Ionic Liquids in Synthesis, eds. P. Wasserscheid and T. Welton,
Wiley-VCH, Weinheim, 2003; (b) C. M. Gordon, Appl. Catal. A: Gen.,
2001, 222, 101; (c) H. Olivier-Bourbigou and L. Magna, J. Mol. Catal.
A: Chem., 2002, 182–183, 419; (d) T. Welton, Coord. Chem. Rev.,
2004, 248, 2459; (e) Z. C. Zhang, Adv. Catal., 2006, 49, 153; (f) S. Liu
and J. Xiao, J. Mol. Catal. A: Chem., 2007, 270, 1; (g) J. Ranke, S. Stolte,
R. Stormann, J. Arning and B. Jastorff, Chem. Rev., 2007, 107, 2183.
E. Mizushima, T. Hayashi and M. Tanaka, Topics Catal., 2004, 29, 163.
A. L. Lapidus, O. L. Eliseev, N. N. Stepin and T. N. Bondarenko, Izv.
Akad. Nauk, Ser. Khim., 2004, 2458 (Russ. Chem. Bull., Int. Ed., 2004,
53, 2564).
PhCH2Cl + H2
Indeed, we observed positive correlation between Pd black
precipitated in the reactor and toluene yield in each run. In run 3,
GC analysis revealed 0.04 vol.% CO2 in a gas phase when the
reaction was complete. However, the calculated yield of H2 in
WGS reaction proved to be 3.5%, somewhat less than the yield
of toluene in run 3.
Decreasing palladium concentration in the reaction mixture
is known to improve specific activity of the catalyst (i.e.,
amount of product formed per mole of metal charged) in the
Heck reaction.10 In order to reach maximal TOF value in our
reaction, catalyst amount was decreased to 0.05 mol% based on
substrate. In NBu4Br medium, phenylacetic acid yield was of
34% in 2 h run, corresponding average TOF 340 h–1. In NBu4Cl
medium, 47% yield was reached with average TOF 470 h–1. For
comparison, phenylacetic acid was obtained4 with the yield of
47% in a 24 h experiment, giving TOF value of about 2.
The question about stabilization of zero-valent palladium in
the reaction mixture is open. Somewhat speculatively, highly
dispersed Pd particles can be formed in NBu4Hal melt, similar
to those found in the Heck reaction.10 Another way is the formation
of [Pd2(CO)nHalm]m– complexes with bridging CO ligands.11
A number of benzyl halides were successively converted
into correspondent arylacetic acids.† Note that considerable
amount of toluene (23% yield) was formed in benzyl bromide
2
3
4
5
6
7
A. Lapidus, O. Eliseev, T. Bondarenko and N. Stepin, J. Mol. Catal. A:
Chem., 2006, 252, 245.
O. L. Eliseev, N. N. Stepin, T. N. Bondarenko and A. L. Lapidus, Dokl.
Akad. Nauk, 2005, 401, 486 [Dokl. Chem. (Engl. Transl.), 2005, 401,
59].
O. L. Eliseev, T. N. Bondarenko, N. N. Stepin and A. L. Lapidus,
Mendeleev Commun., 2006, 107.
†
Catalytic runs were carried out in a pressurized 50 ml Hastelloy lined
8
9
steel reactor equipped with a magnetic stirrer, arrangements for automatic
temperature control and pressure regulation. The reactor was charged
with 4 mmol of substrate, appropriate amounts of Pd(OAc)2, 8 mmol of
water and molten salt, flushed with CO and filled with CO up to desired
pressure. Then, the stirrer was switched on and the reactor was heated to
110 °C. Upon CO consumption, the pressure was maintained constant
by automatic pressure regulator. After reaction complete the reactor was
cooled to ambient temperature and depressurized, the reaction mixture
was extracted with diethyl ether and analyzed by GC.
N. N. Stepin, PhD Thesis, Moscow, IOC RAS, 2008.
10 M. T. Reetz and J. G. de Vries, Chem. Commun., 2004, 1559.
11 A. V. Kulik, O. N. Temkin, L. G. Bruk, V. E. Zavodnik, V. K. Belsky
and V. V. Minin, Izv. Akad. Nauk, Ser. Khim., 2005, 1349 (Russ. Chem.
Bull., Int. Ed., 2005, 54, 1391).
Received: 3rd April 2009; Com. 09/3316
– 257 –