Mild and general procedure for Pd/C-catalyzed hydrodechlorination of aromatic chlorides

Article abstract of DOI:10.1016/S0040-4039(02)01622-2

A mild and efficient one-pot hydrodechlorination using a Pd/C-Et₃N system proceeds at room temperature, which is general for the dechlorination of a variety of aromatic chlorides.

Full text of DOI:10.1016/S0040-4039(02)01622-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 7247–7250
Mild and general procedure for Pd/C-catalyzed
hydrodechlorination of aromatic chlorides
Hironao Sajiki,* Akira Kume, Kazuyuki Hattori and Kosaku Hirota*
Laboratory of Medicinal Chemistry, Gifu Pharmaceutical University, 5-6-1 Mitahora-higashi, Gifu 502-8585, Japan
Received 13 June 2002; revised 22 July 2002; accepted 26 July 2002
Abstract—A mild and efficient one-pot hydrodechlorination using a Pd/C–Et3N system proceeds at room temperature, which is
general for the dechlorination of a variety of aromatic chlorides. © 2002 Elsevier Science Ltd. All rights reserved.
Dehalogenation reactions of aromatic halides have
important synthetic and environmental potential and
can be achieved by a variety of chemical methods.1 It is
well known that aromatic chlorides are much less reac-
tive than aromatic bromides and iodides and hence, the
dechlorination of aromatic chlorides cannot readily be
achieved.1–3 Therefore, the development of new dechlo-
rination methods remains a topic of great interest. The
dechlorination of aromatic chlorides is an underdevel-
oped methodology, and few effective general methods
are available.2,4 Existing techniques usually utilize
hydride reduction,5 hydrogenation,6 dechlorination
using metals,7 photolysis,8 oxidation,9 or electrolysis.10
Many such reactions require high heat, high pressure,
radiation, stoichiometric reagents, vast amounts of cat-
alyst, special equipment and/or strongly basic condi-
tions, and most of the reactions are very frequently
incomplete. Herein, we describe a general procedure for
the palladium on carbon (Pd/C)-catalyzed hydrodechlo-
rination of aromatic chlorides that operate under mild
conditions at room temperature and is applicable to the
dechlorination of a variety of aromatic chlorides.
genation of other reducible functionalities such as
olefin, Cbz, benzyl ester, azide and so on.11 During the
course of our further study on the chemoselective
hydrogenation using the Pd/C–Et3N system, we found
that the catalytic activity of Pd/C toward the
hydrodechlorination of only aromatic chlorides was
remarkably and selectively activated by the addition of
Et3N, contrary to our expectation. Although it is sug-
gested that dechlorination of aromatic chlorides cannot
readily be achieved,1–3 both the conversion yield and
the reaction rate of the dechlorination of 4-chloro-
biphenyl (1 in Scheme 1 and Fig. 1) could be brought to
outstanding levels by running the hydrodechlorination
using commercial 10% Pd/C (3% of the weight of 1)
and 1.2 equiv. of Et3N in MeOH at room temperature
and under hydrogen pressure. The reaction was com-
pleted smoothly within 1 h to afford the corresponding
biphenyl 2 in 100% conversion yield (GC/mass) and no
products other than 2 were detected by GC/mass
although the dechlorination was incomplete even after
3 days when the reaction was carried out without Et3N
(Fig. 1).
Recently, we have reported that addition of a nitrogen-
containing base (e.g. NH3, pyridine, ammonium ace-
tate) to a Pd/C-catalyzed hydrogenation system as a
weak catalyst poison chemoselectively inhibited the
hydrogenolysis of a benzyl ether with smooth hydro-
Dechlorination of 4-chlorobiphenyl (1) was carried out
using various nitrogen-containing bases and solvents
(Table 1). Typically, the reaction was carried out under
ordinary hydrogen pressure (balloon) using 1.2 equiv.
Scheme 1. Hydrodechlorination of 1 in the presence of Et3N.
* Corresponding authors.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)01622-2

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H. Sajiki et al. / Tetrahedron Letters 43 (2002) 7247–7250
Figure 1. Kinetics plots on the hydrodechlorination of 4-chlorobiphenyl 1 using 10% Pd/C (3% of the weight of 4-chlorobiphenyl
1) with or without Et3N (1.2 equiv.) in MeOH under a hydrogen atmosphere at room temperature (ca. 20°C).
Table 1. Assessment of nitrogen-containing bases and sol-
vents in the dechlorination of 4-chlorobiphenyl (1)a
matized heterocyclic base such as pyridine or quinoline
was used as a base, the hydrodechlorination was abso-
lutely suppressed and no reaction was observed (entries
14 an 15). These facts rule out the possibility that Et3N,
an effective base, acts only as a scavenger of the
generated hydrogen chloride. Thorough optimization of
the reaction conditions eventually revealed that initial
treatment of the methanol solution of 1 with 10% Pd/C
(3% of the weight of 1) and Et3N (1.2 equiv.) at room
temperature for 1 h under ordinary hydrogen pressure
(balloon) proved to be the best reaction conditions.
Entry
Base
Solvent
Yield of 2 (%)b
1
2
3
4
None
NH3
NH2(CH2)2NH2
Me2NH
Et3N
Et3N
Et3N
Et3N
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
THF
24
67
94
100c
100c
100c
4
5
6d
7e
8
43
9
Et3N
Et3N
Et3N
DBU
PhNH2
Pyridine
Quinoline
Hexane
DMF
H2O
MeOH
MeOH
MeOH
MeOH
63
3
0
To explore the scope of this method, the hydrodechlori-
nation of a variety of aromatic chlorides was investi-
gated (Table 2). The results shown entries 1, 2 and 4
demonstrated that the reaction could be carried out in
the presence of carboxylic acid and phenolic functional-
ities. Competitive reduction of the nitro moiety of
2-chloro-4-nitrotoluene was observed and the product
was isolated as 4-toluidine in 90% isolated yield (entry
6), while the aromatic ketone moiety of 4-chloroben-
zophenone remained somehow intact and the corre-
sponding benzophenone was quantitatively generated
(entry 3). In addition, some medicines such as
indometacin (entry 7), clofibrate (entry 8) and
hydrochlorothiazide (entry 9) were efficiently processed,
although a prolonged reaction time was required.
10
11
12
13
14
15
100c
100c
0
0
a All reactions were carried out under ordinary hydrogen pressure
(balloon) using 1.2 equiv. of a nitrogen-containing base and 10%
Pd/C (3% of the weight of the aromatic chloride) in a solvent at
room temperature.
b Yields were determined by GC/MS.
c No other products were detected by GC/MS.
d Under dark conditions.
e The reaction was carried out at −20°C.
There is little doubt that Et3N is not only a scavenger
of hydrogen chloride but also a strong activator of the
Pd/C-catalyzed hydrodechlorination process (see Table
1). Moreover, addition of a small amount of TCNE
(tetracyanoethylene) or TCNQ (7,7,8,8-tetractano-
quinodimethane), a single electron capture, to the
hydrodechlorination reaction mixture in the presence of
Et3N thoroughly suppresses the reaction, suggesting the
participation of a single electron transfer (SET) mecha-
nism in the simple catalytic process (Scheme 2). Initial
single electron transfer to the palladium-activated
chlorobenzene ring of A from Et3N affords anion radi-
cal B, which may then convert to the dechlorinated
benzene ring of C by subsequent elimination of the
chloride anion.
of a nitrogen-containing base and 10% Pd/C (3% of the
weight of the aromatic chloride) in a solvent at room
temperature and the products were detected by GC/MS
and NMR after simple extraction. The use of MeOH as
a solvent was found to dramatically improve the reac-
tivity of the hydrodechlorination reaction (entries 5 and
8–11). The results shown in entries 4, 5, 12 and 13
demonstrate that the dechlorination can be carried out
using relatively lipophilic amines. The dechlorination
using Et3N took place even under dark conditions
(entry 6). The efficiency of the catalytic system was
drastically decreased at low temperature (−20°C, entry
7). In addition, aniline, an aromatic amine, was also
efficiently processed (entry 13), although, when an aro-

H. Sajiki et al. / Tetrahedron Letters 43 (2002) 7247–7250
Table 2. 10% Pd/C–Et3N-mediated dechlorination of aromatic chloridesa
7249
Acknowledgements
This work was supported by a Grant-in Aid for Scien-
tific Research from the Ministry of Education, Science,
Sports, and Culture, of the Japanese Government (No.
13672222), the Research Foundation for Pharmaceuti-
cal Sciences and the Research Foundation for the Elec-
trotechnology of Chubu.
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