Pd/C-catalyzed room-temperature hydrodehalogenation of aryl halides with hydrazine hydrochloride

Article abstract of DOI:10.1016/S0040-4039(03)01789-1

Treatment of aryl and heteroaryl halides with catalytic amounts of Pd/C in the presence of hydrazine hydrochloride in basic medium (sodium hydroxide or sodium t-butylate) at room temperature leads to the corresponding hydrodehalogenation products with high selectivity. Aryl iodides, bromides, chlorides and fluorides can be reduced using this reagent combination. The reduction is compatible with various electron-donating or electron-withdrawing groups.

Full text of DOI:10.1016/S0040-4039(03)01789-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7191–7195
Pd/C-catalyzed room-temperature hydrodehalogenation of aryl
halides with hydrazine hydrochloride
a
b
a,
a,
Pascal P. Cellier, Jean-Francis Spindler, Marc Taillefer * and Henri-Jean Cristau *
a
Laboratoire de Chimie Organique, ENSCM (UMR 5076), 8 rue de l’Ecole Normale, 34296 Montpellier cedex 5, France
b
RHODIA Organique Fine, Centre de Recherches de Lyon, 85 avenue des Fr e` res Perret, BP 62, 69192 Saint-Fons Cedex,
France
Received 9 May 2003; revised 18 July 2003; accepted 23 July 2003
Abstract—Treatment of aryl and heteroaryl halides with catalytic amounts of Pd/C in the presence of hydrazine hydrochloride in
basic medium (sodium hydroxide or sodium t-butylate) at room temperature leads to the corresponding hydrodehalogenation
products with high selectivity. Aryl iodides, bromides, chlorides and fluorides can be reduced using this reagent combination. The
reduction is compatible with various electron-donating or electron-withdrawing groups.
©
2003 Published by Elsevier Ltd.
The conversion of aryl halides into arenes is a chemical
transformation with important industrial applications.
The detoxification of halogenated aromatic wastes, like
polychlorinated biphenyls (PCBs), by catalytic
hydrodehalogenation is indeed an environmentally
friendly and cost-saving alternative to their traditional
disposal by incineration, which can generate highly
The Pd-catalyzed hydrogenolysis of carbonꢀhalogen
bonds with hydrazine as a hydrogen donor is a long-
known method, but it is usually performed with large
6
,7
amounts of catalyst and/or reducing agent. To our
knowledge, no systematic study of the reaction has
appeared in literature. Moreover, the use of catalytic
palladium in combination with reduced amounts of
hydrazine under mild conditions was only achieved by
1
toxic dibenzofurans and dibenzodioxins. This transfor-
8
mation has also been used for the selective deuterium
Balko et al. and is restricted to chlorophenols. Thus,
2
or tritium labeling of arenes and is of interest in
we decided to investigate the scope and limitations of
this methodology and to establish the optimum reac-
tion conditions.
organic synthesis, since a halogen atom can serve as a
protecting group for an aryl site or direct electrophilic
3
substitutions.
We chose to use hydrazine as its hydrochloride salt for
safety reasons, since this form is less dangerous and
more easy to handle than the anhydrous or the hydrate
forms. A preliminary survey of catalytic efficiency of
different palladium sources was first undertaken on the
model reaction involving 4-bromotrifluoromethylben-
zene as the substrate, sodium t-butylate as the base and
THF as the solvent (Table 1). Although effective proto-
cols using metal catalysts in combination with sophisti-
cated N-heterocyclic carbene ligands have been
A wide variety of hydrodehalogenating systems have
been used over the years and this subject has recently
4
been reviewed in detail. Reduction is usually mediated
5
by a transition-metal catalyst (Ni, Pd, Rh, Pt) and is
performed with molecular hydrogen, metal hydrides or
hydrogen sources such as formic acid and its salts,
hydrazine or alkoxides possessing a b-hydrogen. For
safety and simplicity of operation, a liquid-phase pro-
cess without using molecular hydrogen is more
advantageous.
2b,5d
developed recently,
we preferred a methodology
employing no additional ligand for economic reasons.
Pd/C and Pd (dba) allowed quasi selective hydrode-
2
3
halogenations within 24 h at room temperature (Table
, entries 1 and 2), while the use of palladium acetate
1
favoured biaryl reductive coupling (entry 3). As
expected, reactions performed without a palladium cat-
alyst resulted in no detectable reduction product (entry
4). The less expensive and far more efficient Pd/C was
Keywords: liquid-phase dehalogenation; palladium catalyst; heteroge-
neous catalysis; aryl halides; hydrazine.
*
Corresponding authors. E-mail: taillefe@cit.enscm.fr; cristau@
cit.enscm.fr
0
040-4039/$ - see front matter © 2003 Published by Elsevier Ltd.
doi:10.1016/S0040-4039(03)01789-1

7
192
P. P. Cellier et al. / Tetrahedron Letters 44 (2003) 7191–7195
a
Table 1. Effect of palladium source on the reduction of 4-bromotrifluoromethylbenzene with hydrazine
Entry
Catalyst
Arene yield (%)
Arene selectivity (%)b
Biaryl yield (%)
1
2
3
4
Pd/C
94
66
38
0
94
93
38
–
6
4
62
0
Pd (dba)
2
3
Pd(OAc)2
–
a
Yields determined by GC by obtaining the correction factors using authentic samples of the products.
Arene yield divided by aryl bromide conversion.
b
preferred to Pd (dba) and used in experiments aimed
at optimizing the hydrazine quantity and the nature of
base and solvent (Table 2), employing the electron-rich
and sodium t-butylate were the most efficient (entries 5
and 6). K PO , KOt-Bu, LiOt-Bu, K CO and Cs CO
3
2
3
3
4
2
3
2
all led to incomplete conversions of the starting mate-
rial (Table 2, entries 7–11). These variations in yields
imply that the role of base compounds is not limited to
neutralization of halogenohydric acid. Due to its lower
cost and its slightly higher selectivity in favour of the
4-chloroanisole as a more challenging model substrate.
We found that the minimum amount of reducing agent
compatible with a high ratio hydrodehalogenation/
homocoupling (94%) was 0.75 equiv. relative to the aryl
chloride (Table 2, entries 1–4). Lowering this amount to
9
hydrodehalogenation product, sodium hydroxide was
chosen to investigate the effect of solvent on the reac-
tion outcome. Toluene and THF were found to be the
solvents of choice (Table 2, entries 12 and 13), allowing
quasi quantitative conversion of 4-chloroanisole to
anisole in less than 24 h. Reactions were slightly less
selective in ethanol while poor yields were observed in
acetonitrile or dichloromethane (entries 14–16).
0
4
.5 equiv. also allowed a quantitative reduction of
-chloroanisole but resulted in a decrease of the selec-
tivity towards anisole (86%) and revealed rate-depress-
ing (Table 2, entry 4). Interestingly, this experiment
proved that the palladium catalyst generates 2 equiv. of
hydrogen from 1 equiv. of hydrazine.
A variety of bases were then examined in THF with a
reaction time fixed to 48 h. Of these, sodium hydroxide
Using the optimized reaction conditions (Table 2, entry
12), a broad sampling of functionalized substrates were
a
Table 2. Effect of hydrazine quantity and base or solvent nature on the hydrodehalogenation of 4-chloroanisole
Entry
Base
Solvent
Time (h)
Equiv.
[ArX] (mol/L) Anisole yield
Anisole
4,4%-Bianisole yield
N H ·HCl
(%)
selectivity (%)b (%)
2
4
1
2
3
4
5
6
7
8
9
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOt-Bu
NaOH
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
THF
Toluene
THF
EtOH
CH Cl
55
24
24
24
48
48
48
48
48
48
48
24
24
24
24
24
2
1
0.75
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
1.0
1.0
1.0
1.0
1.0
100
94
94
86
99
94
86
73
45
29
17
>99
99
96
15
2
100
94
94
86
99
94
95
97
87
84
84
>99
99
96
0
6
6
14
1
6
5
2
7
6
4
<1
1
4
0
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
0.75
NaOt-Bu
K PO4
3
KOt-Bu
K CO3
2
10
11
12
13
14
15
16
Cs CO3
2
LiOt-Bu
NaOH
NaOH
NaOH
NaOH
NaOH
100
100
2
2
MeCN
0
a
Yields determined by GC by obtaining the correction factors using authentic samples of the products.
Anisole yield divided by chloroanisole conversion.
b

P. P. Cellier et al. / Tetrahedron Letters 44 (2003) 7191–7195
7193
hydrodehalogenated with good to excellent yields
ing arenes with equal efficiency within 24 h. Heteroaro-
matics such as 3-bromopyridine or 2-bromothiophene
(Table 3, entries 17 and 18) behaved similarly. We
found that the ratio hydrodehalogenation/homocou-
1
0
(
Table 3). Electron-rich (entries 1 and 2), electron-
poor (entries 6–9) and sterically hindered (entry 11) aryl
chlorides or bromides were reduced to the correspond-
Table 3. Palladium-catalyzed hydrodehalogenation of aromatic and heteroaromatic halides
a
In THF.
b
After hydrolysis of the reaction mixture with 35% HCl at rt.
c
With 6 equiv. of NaOH and 2.5 equiv. of N H ·HCl.
2
4
d
e
f
2
1% azobenzene were formed.
Reaction time: 30 h.
With 0.5 equiv. of N H ·HCl.
2
4
g
h
Reaction times are not optimized.
Arene yield divided by aryl halide conversion.

7
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P. P. Cellier et al. / Tetrahedron Letters 44 (2003) 7191–7195
pling was sensitive to the nature of halogen and
decreased when going from chlorine to iodine. Thus,
entry 15). Aniline was obtained with a 74% yield and
the incompletely reduced azobenzene was formed as a
side product (21%).
4-chloranisole and 4-bromoanisole were reduced to
anisole with >99 and 97% yield respectively, while
4
4
-iodoanisole afforded 78% anisole along with 22%
A possible pathway for hydrodehalogenations mediated
,4%-bianisole (entries 1–3). In the latter case, using
by the system Pd/C/N H /NaOH is depicted by Scheme
2
4
THF instead of toluene as the solvent further decreased
the yield of anisole to 29% (entry 5). As expected, the
incidence of biaryl coupling could be reduced by dilut-
ing the reaction mixture (compare entries 4 and 16 with
entries 5 and 17).
1. The first step involves oxidative addition of the aryl
5b
halide to a zerovalent palladium complex (generated
from Pd/C with hydrazine), followed by base-assisted
displacement of the halogen atom by hydrazine.
Decomposition of the palladium-bonded hydrazide into
12
diimine N H via b-H elimination leads to a palla-
2
2
2
b
As previously stated in literature, the reactivity of aryl
halides was found to follow the order of bond strength:
ArI>ArBr>ArCl, as deduced from entries 12 and 13.
dium hydride complex from which the Pd(0) catalyst is
regenerated by reductive elimination of the arene. The
likely evolved dihydrogen also takes part to this process
in a similar fashion, accounting for the fact that a 0.5
equiv. of hydrazine can reduce 1 equiv. amount of aryl
halide to the corresponding arene.
4
-Chlorobromobenzene was reduced to chlorobenzene
(
53% yield, 86% selectivity), along with benzene (6%)
and chlorinated biaryl compounds (ꢀ3%). Iodine
removal from 4-iodobromobenzene took place prefer-
entially, affording bromobenzene as the main product
In summary, we have shown that the conversion of aryl
iodides, bromides, chlorides and even fluorides to the
corresponding arenes can be efficiently performed in
toluene at room temperature in the presence of a slight
excess of hydrazine as a cheap hydrogen donor, sodium
hydroxide and catalytic amounts of Pd/C without sup-
porting ligand. Worthy of note is the fact that some
sensitive functional groups like nitrile and ketone are
tolerated on the aryl halides. The method is mild,
operationally simple (no pressure apparatus is required)
and enjoys benefits associated with heterogeneous
catalysis.
(
42% yield, 64% selectivity). 2% benzene and ꢀ9%
brominated biaryl compounds were also formed in this
case. Due to the high strength of the carbonꢀfluorine
bond, aryl fluorides usually exhibit a relative inertness
1
1
4,5d,e
in metal-catalyzed reactions.
Therefore, we were
pleased to find that they were also prone toward our
room-temperature hydrodehalogenation protocol. Ben-
zene was obtained from fluorobenzene as the sole
product in 51% yield within 24 h (Table 3, entry 14).
Nitrile and ketone functions (Table 3, entries 8 and 9)
were not reduced by hydrazine, attesting the functional
group compatibility offered by the present method. In
the case of 4-bromoacetophenone (entry 9), the crude
reaction mixture had to be treated with concentrated
HCl at room temperature to hydrolyze the azines
formed from the reaction of hydrazine with two ace-
tophenone molecules. We could reduce both nitro and
bromine groups of 3-bromonitrobenzene using 2.5
equiv. of hydrazine relative to the aryl halide (Table 3,
Acknowledgements
Rhodia Organique Fine is gratefully acknowledged for
the financial support of this work.
References
1
. (a) Menini, C.; Park, C.; Shin, E.-J.; Tavoularis, G.;
Keane, M. A. Catal. Today 2000, 62, 355–366; (b) King,
C. M.; King, R. B.; Bhattacharyya, N. K.; Newton, M.
G. J. Organomet. Chem. 2000, 600, 63–70.
2
. (a) Dorman, G.; Otszewski, J. D.; Prestwich, G. D. J.
Org. Chem. 1995, 60, 2292–2297; (b) Desmarets, C.;
Kuhl, S.; Schneider, R.; Fort, Y. Organometallics 2002,
2
1, 1554–1559; (c) Faucher, N.; Ambroise, Y.; Cintrat,
J.-C.; Doris, E.; Pillon, F.; Rousseau, B. J. Org. Chem.
002, 67, 932–934.
. (a) Zask, A.; Helquist, P. J. Org. Chem. 1978, 43, 1619–
620; (b) Debarge, S.; Violeau, B.; Bendaoud, N.; Jouan-
netaud, M.-P.; Jacquesy, J.-C. Tetrahedron Lett. 2003, 44,
747–1750.
. Alonso, F.; Beletskaya, I. P.; Yus, M. Chem. Rev. 2002,
02, 4009–4091.
. For recent reports, see: (a) Lipshutz, B. H.; Tomioka, T.;
Pfeiffer, S. S. Tetrahedron Lett. 2001, 42, 7737–7740; (b)
Lipshutz, B. H.; Tomioka, T.; Sato, K. Synlett 2001,
970–973; (c) Ukisu, Y.; Kameoka, S.; Miyadera, T. Appl.
Catal., B 2000, 27, 97–104; (d) Viciu, M. S.; Grasa, G. A.;
2
3
1
1
4
5
1
Scheme 1. Possible mechanism for the palladium-catalyzed
hydrodehalogenation of aryl halides with hydrazine.

P. P. Cellier et al. / Tetrahedron Letters 44 (2003) 7191–7195
7195
Nolan, S. P. Organometallics 2001, 20, 3607–3612; (e)
Young, R. J., Jr.; Grushin, V. V. Organometallics 1999,
10. Typical procedure: Under an atmosphere of dry and pure
nitrogen, an oven-dried Schlenk tube equipped with a
magnetic stir bar was charged with 10% w/w Pd/C (26
mg, 0.025 mmol Pd, Fluka), hydrazine hydrochloride (26
mg, 0.375 mmol), sodium hydroxide (40 mg, 1 mmol) and
the aryl halide (0.5 mmol), if a solid. The tube was
capped with a rubber septum. If a liquid, the aryl halide
was added via syringe, followed by anhydrous toluene (1
mL). The septum was removed and the tube was sealed
under a positive pressure of nitrogen. The slurry was
allowed to stir for 24 h at room temperature. The reac-
tion mixture was then diluted with dichloromethane (5
mL) and a known volume of internal standard was
added. A small sample of this mixture was filtered
1
8, 294–296; (f) Sajiki, H.; Kume, A.; Hattori, K.;
Hirota, K. Tetrahedron Lett. 2002, 43, 7247–7250; (g)
Rahaim, R. J., Jr.; Maleczka, R. E., Jr. Tetrahedron Lett.
2
002, 43, 8823–8826; (h) Refs. 1, 2, 7.
6
7
8
. (a) Busch, M.; Schmidt, W. Ber. Dtsch. Chem. Ges. 1929,
62, 2612–2620; (b) Busch, M.; Weber, W. J. Prakt. Chem.
1936, 146, 1–55; (c) Mosby, W. L. J. Org. Chem. 1959,
24, 421–423.
. New examples were reported after the completion of this
work. See: (a) Rodriguez, J. G.; Lafuente, A. Tetrahedron
Lett. 2002, 43, 9645–9647; (b) Rodriguez, J. G.; Lafuente,
A. Tetrahedron Lett. 2002, 43, 9581–9583.
®
. (a) Balko, E. N.; Hoke, J. B.; Gramiccioni, G. A. US
through a plug of Celite , washed three times with water
Patent 5,177,268, 1993; Chem. Abstr. 1993, 119, 188209;
and analyzed by gas chromatography.
11. No attempts were made to optimize the reduction of
dihalogenated aromatics.
12. Corey, E. J.; Mock, W. L.; Pasto, D. J. Tetrahedron Lett.
1961, 2, 347–352.
(b) Kovenklioglu, S.; Balko, E. N.; Hoke, J. B.; Farrauto,
R. J.; Gramiccioni, G. A. US Patent 5,196,617, 1993;
Chem. Abstr. 1993, 119, 79294.
. Used as 20–40 mesh beads (Aldrich Chem. Co.).
9