The ionic liquid [bmim]Br as an alternative medium for the catalytic cleavage of aromatic C-F and C-Cl bonds

Article abstract of DOI:10.1016/j.tetlet.2010.02.104

The potential of [bmim]Br as an alternative to aprotic dipolar solvents in nickel-catalyzed hydrodehalogenation reactions is demonstrated. Hydrodechlorination of pentafluorochlorobenzene proceeds under the action of zinc in aqueous [bmim]Br. Under the above conditions aromatic C-F bonds also undergo slow cleavage. The reaction is significantly accelerated in the presence of nickel complexes with 2,2′-bipyridine or 1,10-phenanthroline. In the case of pentafluoroacetanilide highly regioselective ortho-hydrodefluorination leading to the formation of 3,4,5-trifluoroacetanilide is observed.

Full text of DOI:10.1016/j.tetlet.2010.02.104

Tetrahedron Letters 51 (2010) 2265–2268
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Tetrahedron Letters
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The ionic liquid [bmim]Br as an alternative medium for the catalytic cleavage
of aromatic C–F and C–Cl bonds
*
Sergey A. Prikhod’ko, Nicolay Yu. Adonin , Valentin N. Parmon
G. K. Boreskov Institute of Catalysis SB RAS, Lavrent’ev ave., 5, 630090 Novosibirsk, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The potential of [bmim]Br as an alternative to aprotic dipolar solvents in nickel-catalyzed hydrodehalo-
genation reactions is demonstrated. Hydrodechlorination of pentafluorochlorobenzene proceeds under
the action of zinc in aqueous [bmim]Br. Under the above conditions aromatic C–F bonds also undergo
Received 22 December 2009
Revised 9 February 2010
Accepted 19 February 2010
Available online 23 February 2010
0
slow cleavage. The reaction is significantly accelerated in the presence of nickel complexes with 2,2 -
bipyridine or 1,10-phenanthroline. In the case of pentafluoroacetanilide highly regioselective ortho-hyd-
rodefluorination leading to the formation of 3,4,5-trifluoroacetanilide is observed.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
Ionic liquids
Nickel complex
0
2
,2 -Bipyridine
1
,10-Phenanthroline
Zinc
Catalysis
Hydrodehalogenation
10
Incompletely halogenated aromatic compounds are useful sub-
reaction),8,9 carbonylation reactions, nickel-catalyzed homocou-
1
11
strates and precursors in a wide range of organic reactions includ-
pling reactions as well as catalytic hydrodehalogenation of aryl ha-
2
12
ing the preparation of various functional materials. Partially
lides.
However, there are no known examples of catalytic
fluorinated aromatic compounds are of particular interest for the
synthesis of biologically active substances.3 An approach to the
synthesis of incompletely halogenated compounds is based on
the selective removal of one or more of the halogen atoms from
fully halogenated substrates, which are more readily available for
example in the case of polyfluorinated compounds.4 Hence, the
development of new methods for selective hydrodehalogenation
of aromatic polyhalides is an interesting topic.
activation of aromatic C–F bonds in ionic liquids. In the present work
we have found that an ionic liquid can be used as the reaction med-
ium for the nickel-catalyzed activation of C–F and C–Cl bonds of aro-
matic polyfluorides.
Previously, we reported that hexafluorobenzene (1), octafluoro-
13
naphthalene (2), pentafluoropyridine (3), pentafluorobenzoic acid
1
4
(4) or their derivatives, as well as pentafluoroaniline deriva-
1
5,16
tives,
undergo hydrodefluorination under the action of zinc in
Ionic liquids (ILs) are low melting organic salts with properties
useful in synthetic chemistry, catalysis, materials science, etc. ILs
the presence of catalytic amounts (5 mol % of the substrate) of nickel
complexes with 2,2 -bipyridine (Bpy) or 1,10-phenanthroline
5
0
are good solvents of both organic and inorganic substrates. In addi-
tion, the use of ionic liquids as solvents for transition metal cata-
lyzed organic reactions makes it possible to isolate easily
reaction products from the reaction mixtures and to recycle the
catalyst-ionic liquid system.5
(Phen). Mixtures of polar aprotic solvents (DMF, DMA or NMP) and
water were used as the reaction media. The reaction pathway de-
pends on the nature of the solvent, the catalytic complex and the
substrate-zinc molar ratio. In the present work we studied the cata-
lytic hydrodehalogenation reactions of polyfluorinated substrates in
aqueous 1-butyl-3-methylimidazolium bromide ([bmim]Br).
We previously found that nickel complexes with two and three
Numerous studies have been reported which describe catalytic
reactions in ionic liquids.5 At the same time, only a few examples
of the catalytic activation of C–Hal bonds in aromatic halides are
known to date with most being palladium-catalyzed reactions of
,6
0
molecules of 2,2 -bipyridine or 1,10-phenanthroline as the ligands
possessed the highest activity among the corresponding coordina-
7
,8
16
aryl halides with unsaturated compounds (Heck reaction), palla-
dium-catalyzed reactions with organoboron compounds (Suzuki
tion compounds of nickel. Therefore we chose the complexes
NiCl
2
ꢀ3Bpy and NiCl ꢀ2Phen as catalysts for the hydrodehalogen-
2
ation. Hexafluorobenzene (1) undergoes smooth hydrodefluorina-
tion under reductive conditions in the presence of catalytic
amounts of the nickel complexes in aqueous [bmim]Br to give a
*
Corresponding author. Tel.: +7 383 330 78 31; fax: +7 383 330 80 56.
E-mail address: adonin@catalysis.ru (N.Yu. Adonin).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.02.104

2
266
S. A. Prikhod’ko et al. / Tetrahedron Letters 51 (2010) 2265–2268
X
F
F
F
F
F
F
F
F
F
F
F
F
F
F
Catalyst
O, [bmim]Br,
0 °C, 7 h
+
+
+
Zn, H
F
F
F
2
F
1
F
F
F
7
(X=F)
6
7
8
9
1
3 (X=Cl)
4
(X=COOH)
F
F
F
+
+
+
F
F
F
F
10
11
12
Scheme 1.
Table 1
Hydrodehalogenation of polyfluoroaromatic compounds 1, 13, and 4 in aqueous [bmim]Br17
Entry
Substrate
Catalyst
None
Conversion, %
Productsa (selectivity, %)
1
2
3
4
5
6
7
8
9
1
1
1
13
13
13
4
35
96
98
100
100
100
100
100
100
6 (99); 7 (1)
NiCl
NiCl
None
2
ꢀ3Bpy
6 (10); 7 (22); 8 (21); 9 (17); 10 (19); 11 (3); 12 (8)
6 (46); 7 (34); 8 (20)
6 (96); 7 (1); 8 (3)
6 (34); 7 (27); 8 (29); 9 (4); 10 (6)
6 (75); 7 (10); 8 (15)
6 (52); 7 (48)
2
ꢀ2Phen
NiCl
NiCl
None
2
ꢀ3Bpy
2
ꢀ2Phen
4
4
NiCl
NiCl
2
ꢀ3Bpy
6 (50); 7 (38); 8 (6); 9 (6)
6 (16); 7 (62); 8 (8); 9 (14)
2
ꢀ2Phen
a
19F NMR data.
mixture of partially fluorinated benzenes 6–12 (Scheme 1; Table 1,
entries 2 and 3). In polyfluorinated benzenes containing at least
one hydrogen atom elimination of the next fluorine atom occurs
at the ortho- and para-positions relative to the hydrogen atoms.
Table 2
1
7
Hydrodehalogenation of pentafluoropyridine (3) in aqueous [bmim]Br
Productsa,b (selectivity, %)
Entry
Catalyst
None
1
2
3
14 (80); 15 (20)
Under comparable conditions NiCl
was less active than NiCl
ꢀ3Bpy (Table 1, entry 2). In the presence
of NiCl
2
ꢀ2Phen (Table 1, entry 3)
NiCl
NiCl
2
ꢀ3Bpy
14 (11); 15 (59); 16 (12); 17 (18)
14 (38); 15 (38); 16 (22); 17 (2)
2
2
ꢀ2Phen
2
ꢀ2Phen a high conversion of 1 was observed, but only
a
Conversion of 3 was 100% in all cases.
F NMR data.
mono- and bis-defluorinated polyfluorobenzenes 6, 7, and 8 were
detected as the reaction products. In the absence of the catalyst
the conversion of 1 was only 35% (Table 1, entry 1) and pentaflu-
orobenzene (6) was the major product.
b
19
Table 3
Hydrodehalogenation of pentafluoroacetanilide 5 in aqueous [bmim]Br
In contrast to hexafluorobenzene (1), pentafluorochlorobenzene
17
(
13) underwent complete hydrodechlorination even in the absence
Entry
Catalyst
None
Time, h
Conversion, %
Productsa (selectivity, %)
of the catalyst (Scheme 1; Table 1, entry 4). This demonstrates that
the aromatic C–Cl bond is much more reactive than the aromatic
C–F bond. Addition of catalytic amounts of NiCl
formation of a mixture of partially fluorinated benzenes 6–10 (Ta-
ble 1, entry 5). In the presence of NiCl
1
2
3
7
0.5
2
0
100
100
—
NiCl
NiCl
2
ꢀ3Bpy
18 (65); 19 (35)
18 (99); 19 (1)
2
ꢀ3Bpy led to the
2
ꢀ2Phen
a
19F NMR data.
2
ꢀ2Phen the formation of only
small amounts of 7 and 8 was observed (Table 1, entry 6).
The hydrodefluorination reaction of pentafluorobenzoic acid (4)
was accompanied by decarboxylation of substrate 4 and partially
fluorinated benzoic acids. Only the formation of fluorinated ben-
zenes 6–9 was observed (Scheme 1; Table 1, entries 7–9). This re-
sult differs from that obtained when the hydrodefluorination of
acid 4 was carried out in DMF.14 In the absence of the nickel com-
plex the formation of pentafluorobenzene (6) and 1,2,4,5-tetraflu-
orobenzene (7) in approximately equal amounts was observed
Table 1, entry 7). The content of product 7 in the reaction mixture
(
was significantly higher than that of the non-catalytic hydrodeflu-
orination reactions of substrates 1 and 13. Hence the hydrodefluo-
rination reaction of 4 is faster than the decarboxylation reaction.
Without the catalyst the para-hydrodefluorination of 4 occurred
1
8
similarly to that of the reaction of acid 4 in DMF and aqueous
1
9
ammonia. Addition of catalytic amounts of NiCl
2
ꢀ3Bpy or NiCl ꢀ2-
2
Phen led to a moderate increase in the selectivity of the ortho-hyd-
rodefluorination reaction, but 1,2,4,5-tetrafluorobenzene (7) was
the major product (Table 1, entries 8 and 9).
F
F
N
F
F
F
F
N
F
F
Catalyst
Zn, H O, [bmim]Br,
70 °C, 7 h
+
2
F
3
14
NHAc
F
NHAc
NHAc
F
F
N
F
F
F
F
N
N
F
F
Catalyst
+
+
+
+
F
F
F
Zn, H O,
F
2
F
F
F
18
F
OH
F
[bmim]Br, 70 °C
F
19
1
5
16
Scheme 2.
17
5
Scheme 3.

S. A. Prikhod’ko et al. / Tetrahedron Letters 51 (2010) 2265–2268
2267
NHAc
F
NHAc
NH2
F
F
NaOH, H O
2
NiCl ·2Phen
2
Zn, H O, [bmim]Br,
F
F
5
2
F
F
F
F
70 °C, 2 h
F
F
19
20
Scheme 4.
In the absence of the catalyst, pentafluoropyridine (3) under-
went two types of transformation with participation of the fluorine
atom at C-4: non-catalytic hydrodefluorination to form 2,3,5,6-tet-
rafluoropyridine (14) and nucleophilic substitution with water to
give 4-hydroxy-2,3,5,6-tetrafluoropyridine (15) (Scheme 2; Table
References and notes
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ꢀ3Bpy was more active than
NiCl
ꢀ2Phen.
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2
Unlike all the above described compounds, pentafluoroacetani-
lide (5) did not react with zinc in the aqueous [bmim]Br without
the catalyst (Table 3, entry 1). In the presence of catalytic amounts
of the nickel complexes highly regioselective activation of the aro-
2.
(a) Babudri, F.; Farinola, G. M.; Naso, F.; Ragni, R. Chem. Commun. 2007, 1003;
(
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3
matic C–F bonds ortho to the NHCOCH group of acetanilide 5 was
observed. 3,4,5-Trifluoroacetanilide (18) was the major product of
the reaction (Scheme 3). A side reaction was the further hydrode-
fluorination of 18 to form 3,4-difluoroacetanilide (19). The rate of
the side reaction depends on the nature of the nickel complex. In
6. (a) Parvulescu, V. I.; Hardacre, C. Chem. Rev. 2007, 107, 2615; (b) Welton,
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the presence of NiCl
achieved in 30 min (Table 3, entry 2). Moreover, 19 was also formed
with a selectivity of 35%. In this case NiCl
2
ꢀ3Bpy, the complete conversion of 5 was
2459.
7.
(a) Kaufmann, D. E.; Nouroozian, M.; Henze, H. Synlett 1996, 1091; (b)
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2
ꢀ2Phen demonstrates the
optimum catalytic activity and selectivity. Compound 5 was con-
sumed completely in 2 h (Table 3, entry 3) and 3,4,5-trifluoroace-
tanilide (18) was obtained with a selectivity of 99%. A method for
the preparation of 3,4,5-trifluoroaniline (20) from pentafluoroace-
(
d) Selvakumar, K.; Zapf, A.; Beller, M. Org. Lett. 2002, 4, 3031; (e) Böhm, V. P.
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2
0
tanilide 5 was developed based on this result (Scheme 4).
10. (a) Mizushima, E.; Hayashi, T.; Tanaka, M. Green Chem. 2001, 3, 76; (b)
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R.; Courtinard, C.; Nedelec, J. Y.; Troupel, M. Chem. Commun. 2003, 1434.
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1
2. (a) Calo, V.; Nacci, A.; Monopoli, A.; Damascelli, A.; Ieva, E.; Cioffi, N. J.
Organomet. Chem. 2007, 692, 4397; (b) Ohlin, C. A.; Beni, Z.; Laurenczy, G.; Ruiz,
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Firouzabadi, H.; Azadi, R. J. Organomet. Chem. 2008, 693, 2469.
with the substrate in two ways. In the first case, the initial oxida-
tive addition of the Ni(0) complex to the C–F bonds leads to the
corresponding organonickel compounds which undergo hydrolysis
with formation of the hydrodehalogenation product.22 The second
13.
Adonin, N. Y.; Starichenko, V. F. Mendeleev Commun. 2000, 10, 60.
1
4. Adonin, N. Y.; Starichenko, V. F. J. Fluorine Chem. 2000, 101, 65.
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15. Prikhod’ko, S. A.; Adonin, N. Y.; Babushkin, D. E.; Parmon, V. N. Mendeleev
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reactive intermediate.14
1
1
6. Prikhod’ko, S. A.; Adonin, N. Y.; Parmon, V. N. Russ. Chem. Bull. 2009, 2234.
7. General procedure: The nickel complexes were synthesized according to the
literature method.23 A 5 ml reaction vessel was charged with 0.025 mmol of
Thus, in the present work we have demonstrated the potential
of [bmim]Br as a solvent for hydrodehalogenation reactions. In
general, chlorine atoms bonded to the aromatic ring are more reac-
tive than fluorine atoms. As a consequence, hydrodechlorination
occurs at a reasonable rate even in the absence of a catalyst,
NiCl
and 0.1 ml of H
2
ꢀ3Bpy or NiCl
2
ꢀ2Phen, 327 mg (5 mmol) of Zn, 0.5 ml of molten [bmim]Br
2
O. The mixture was stirred for 10 min and then 0.5 mmol of the
corresponding substrate was added. The reaction mixture was heated with
stirring at 70 °C. After cooling to ambient temperature the reaction mixture
0
19
whereas the presence of nickel complexes with 2,2 -bipyridine or
was analyzed by
F NMR spectroscopy. The NMR spectra of the
15,24
dehalogenation products were in accord with the literature data.
8. (a) Krasnov, V. I.; Platonov, V. E. Zh. Org. Khim. 1993, 29, 1078 (Chem. Abstr.
994, 120, 191201); (b) Platonov, V. E.; Krasnov, V. I. Zh. Org. Khim. 1994, 30,
1
,10-phenanthroline ligands are required for the activation of
1
aromatic C–F bonds. With pentafluorobenzoic acid, reductive
defluorination was complicated by decarboxylation. Catalytic hyd-
rodefluorination of pentafluoroacetanilide (5) leads to highly regio-
selective formation of 3,4,5-trifluoroacetanilide (18) in high yields.
We have shown that [bmim]Br can serve as an alternative to the
aprotic dipolar solvents.
1
1271 (Chem. Abstr. 1995, 123, 285335).
19. Laev, S. S.; Shteingarts, V. D. J. Fluorine Chem. 1999, 96, 175.
2
0. Preparation of 3,4,5-trifluoroaniline (20):
charged with 300 mg (0.6 mmol) NiCl
ꢀ2Phen, 8.01 g (122.4 mmol) of Zn,
13 ml of molten [bmim]Br and 2.5 ml of H O. The mixture was stirred at 70 °C
for 10 min and 2.76 g (12.3 mmol) of 5 were added. The reaction mixture was
heated with stirring at 70 °C for 2 h and then diluted with 10 ml of CH CN. The
solid was removed by filtration and washed with CH CN. The solvent was
A 25 ml three-necked flask was
2
2
3
3
Acknowledgements
evaporated and the product 18 was triturated with hot EtOAc (5 ꢁ 10 ml). The
combined organics were evaporated under vacuum and the residue was mixed
2
with 50 ml of H O and NaOH was added until pH 13–14. The resulting mixture
This work was supported by the Division of Chemistry and
was stirred for 1 h. The product 20 was isolated by steam distillation, after
which 3,4,5-trifluoroaniline (1.25 g, 70% with respect to starting compound 5)
Material Sciences of the Russian Academy of Sciences (Programme
of complex integration projects, project No. 5.7.5). The 1H and
19
F
was obtained. 1H NMR (CDCl
3
, 300 MHz): d 6.24 (ddd, 2H, J = 9.6, 9.5, 3.9 Hz. 2,
). F NMR (CDCl
, 300 MHz): d ꢂ136.1 (dd, 2F, J = 21.3,
19
6-H), 3.69 (br s, 2H, NH
2
3
NMR spectra were measured in the Collective service center SB RAS
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry SB RAS),
Russian Foundation for Basic Research Grant No. 08-03-01805.
9
.3 Hz, 3,5-F), ꢂ176.0 (tt, 1F, J = 21.3, 5.6 Hz, 4-F).
(
2
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19
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2