Iron(III)-mediated photocatalytic selective substitution of aryl bromine by chlorine with high chloride utilization efficiency

Article abstract of DOI:10.1039/c3cc48246d

An iron(III)-mediated photocatalytic method for the conversion of aryl, heteroaryl and polycyclic aromatic bromides to the corresponding chlorides with high selectivity has been achieved successfully. The mild reaction conditions and high chloride utilization efficiency promise a bright future for chlorination reactions. The Royal Society of Chemistry 2014.

Full text of DOI:10.1039/c3cc48246d

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Iron(III)-mediated photocatalytic selective
substitution of aryl bromine by chlorine
Cite this:DOI: 10.1039/c3cc48246d
with high chloride utilization efficiency†
Received 28th October 2013,
Accepted 31st December 2013
Ying Wang, Lina Li, Hongwei Ji, Wanhong Ma, Chuncheng Chen* and Jincai Zhao
DOI: 10.1039/c3cc48246d
www.rsc.org/chemcomm
An iron(III)-mediated photocatalytic method for the conversion of aryl,
Photocatalytic synthesis provides an alternative green strategy
10
heteroaryl and polycyclic aromatic bromides to the corresponding with great promise in organic chemistry. Iron-based photocatalysis
chlorides with high selectivity has been achieved successfully. The mild has been extensively concerned in environmental science for the
reaction conditions and high chloride utilization efficiency promise a degradation of organic pollutants. However, its application in
11
bright future for chlorination reactions.
selective synthesis is rather scarce, because of the intrinsic unselec-
tivity of the radical-chain reactions in the iron-based photochemistry
in water, in which the unselective OH is always involved. Herein, we
report that iron(III) can efficiently photocatalyze the selective trans-
formation of aryl, heteroaryl and polycyclic aromatic bromides into
the corresponding chlorides with high chloride ion utilization
efficiency in acetonitrile (Scheme 1).
The halogen exchange reaction was carried out under irradiation
with wavelength l > 360 nm and the quantum efficiency under
Aryl halides and heteroaryl halides are of great importance as
starting materials in organic synthesis. Among these halides,
chlorides are highly versatile intermediates, especially for the
modification of aromatic rings to improve the physical and
ꢀ
1
2
1
a,3
biological properties in pharmaceutical
and agrochemical
4
application. Therefore, the development of convenient and
efficient methods for the selective synthesis of aryl and heteroaryl
5
chlorides has attracted considerable attention.
365 nm UV light irradiation was 0.074%. As shown in Fig. 1a, in the
As bromination of arenes is generally more controllable and
regioselective for complex aryl compound synthesis than chlorina-
tion, it is more favorable to achieve chlorination of arenes through
the conversion of the corresponding bromides into chlorides in
presence of FeCl and NaCl, bromobenzene is converted completely to
3
chlorobenzene with 94.3% yield after 10 h of irradiation. Control
experiments indicate that this reaction is attributed to neither thermal
catalytic reaction nor direct photolysis of bromobenzene. When the
6
many situations. To realize these exchange reactions, the toxic and
concentration of FeCl is 1% of the substrate, bromobenzene is still
3
labile compounds including chlorine, chlorous acid and sulfuryl
chloride have been used as chlorine sources. Practically, however, it
is more desirable to use inorganic chloride anions as the chlorine
source. Most of the halide exchanges with chloride ions have been
achieved via exchanges between aryl bromides and chloride salts of
completely transformed. This implies that Fe species is the photo-
catalyst, rather than a stoichiometric reactant (Fig. S1, ESI†). Although
75.4% of the bromobenzene was converted after 3 hour of irradiation
in water, no chlorobenzene was detected. In contrast, when methanol
was chosen as solvent, almost no bromobenzene reacted, which
shows the importance of solvent to the reactivity and selectivity of
Fe-based photocatalytic reaction (Table S1, ESI†).
4,7
the metal catalysts including Cu(I), Ni(II) and Pd(II). These systems
still suffer from some limitations, such as elevated reaction tem-
perature (usually above 100 1C), stoichiometric amount even multi-
ple equivalents of catalyst, requirement of complex ligands as well as
When choosing LiCl, a chloride salt with higher solubility in
acetonitrile than NaCl, as the chlorine source, a nearly identical
halogen exchange rate is observed (Fig. S2 and Table S1, ESI†).
Actually, even without extra chloride ions, the halogen exchange
6a,7,8
the treatment of the toxic heavy metals Cu and Ni.
Due to non-
toxicity and easy availability, iron-based catalysis has been applied
9
À
widely in metal catalysis and organic synthesis. Nonetheless, unlike
reactions still proceed efficiently (Fig. 1b), which means the Cl of
À
Cu and Ni, no successful report on the iron-catalyzed halogen
exchange reactions has been recognized so far.
FeCl
3
itself is able to participate in the reactions and extra Cl for the
Key Laboratory of Photochemistry, Beijing National Laboratory for Molecular
Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190,
China. E-mail: ccchen@iccas.ac.cn; Fax: +86 10-82616495
†
Electronic supplementary information (ESI) available: Details of experiments.
Scheme 1 Iron(III)-mediated photocatalytic bromide–chloride exchange
See DOI: 10.1039/c3cc48246d
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a
3
Table 1 FeCl -catalyzed aryl bromide–chloride exchange reactions
Time
(h)
Conv.
(%)
Select.
(%)
Entry
Substrate 1
Product 2
1
2
10
10
97.8
98.5
96.5
93.0
Fig. 1 (a) Conversion of bromobenzene under different conditions. (b) The
3
halogen exchange in the presence of different amounts of FeCl without addition
of extra chloride (The cutline shows the ratio of the catalyst to the substrate). The
reaction conditions were the same as those for the typical procedure mentioned
3
4
5
6
10
10
10
10
93.5
71.6
87.4
99.1
97.7
98.3
98.9
97.6
in ESI.† The solid symbols denote the decay of the bromides (C/C
hollow symbols represent the corresponding yield of chlorides.
0
) and the
3
À
full coordination of Fe to form [FeCl
6
]
is not necessary. More
interestingly, the final conversion and yield are stoichiometrically
À
À
determined by the amount of Cl in these systems when Cl is not
sufficient, which reveals the high chloride ion utilization efficiency.
It is also noted that the halogen exchange reaction in air is much
faster than that in an Ar atmosphere, while the selectivity did not
change much (Fig. S3, ESI†), indicative of the promotive effect of O2.
5
2.7
6.3
7
4
65.3
4
The bromide ion is nearly quantitatively recovered in the end of the
À
2
reaction. No bromines in high oxidation states such as Br and BrO
8
9
60
2
98.2
12.6
>99
are detected, even in the reaction conducted in air (Fig. S4, ESI†).
To demonstrate the applicability of this new-type photocatalytic
reaction, a variety of aryl bromides with both electron-rich and
electron-deficient substituents were screened, and the results are
summarized in Table 1. The bromine in bromobenzenes with para-
substitution by fluorine, chlorine and phenoxyl can also be selectively
83.1
1
1
0
1
2
2
56.6
35.2
82.0
97.7
b
replaced by chlorine (Table 1, entries 2, 3 and 6). As for the substrate 12
2
2
86.9
33.9
9.3
99.4
b
13
containing more than one bromine atom (1g), all bromine atoms
can be exchanged with chlorine sequentially (Fig. S5, ESI†). For the
14
2
2
86.3
42.7
24.6
85.3
b
chlorobromobenzenes with different substitution positions of Br (1c, 15
1d, 1e), selectivities of the exchange reactions are quite excellent, and
the reaction rates are in the order para > ortho > meta. It is
noteworthy that aromatic substitution of aryl bromides occurs
exclusively in the ipso position, which indicates the good regio-
selectivity of Fe-catalyzed chlorination reaction. The exchange reac- 17
tion of 4-nitro-bromobenzene (1h) exhibits a good selectivity for the
formation of 4-nitro-chlorobenzene at the initial stage of the reaction. 19
Nonetheless, the selectivity decreases gradually with prolonged
irradiation time, concomitantly with an increase of 1,4-dichloro- FeCl in 30 mL of acetonitrile, under irradiation with UV light (l > 360 nm).
1
6
2
62.3
8.8
68.5
b
10
21.8
23.2
1
8
10
10
26.7
15.9
c
>99
a
Reaction conditions: 1.0 mM aryl bromide, 5.0 equiv. NaCl and 0.2 mM
3
b
c
In an argon atmosphere. Without irradiation.
benzene, which is attributed to the further exchange of nitryl of
the formed 4-nitro-chlorobenzene by chlorine (Fig. S6, ESI†).
Some substrates such as methoxyl, hydroxyl and methyl (1i, 1j, (3d, 3e), naphthalenes (3f, 3g), even the electron-deficient pyridine
and 1k) exhibit moderate selectivities when the reactions were (3a), can be converted to their corresponding chlorinated products
performed in air, particularly at high conversion. However, much with high selectivity. The position of bromine atoms has no sig-
higher selectivities were achieved in oxygen-free systems (entries 11, nificant influence on their high selectivity but the conversion rate
1
3 and 15). One reasonable explanation for this might be the rapid (Table S2 and Fig. S7, ESI†).
decomposition of products in an oxygen atmosphere (entries 10, 12 In an attempt to determine the factors related to the reaction rate,
and 14) because of the existence of relative labile hydrogen on the the linear free energy relationship of photocatalytic conversion rates of
side-chain which is susceptible to the O -derived active radicals. bromobenzenes was further analysed. The Hammett plot of the
Inspired by the success of aryl bromide exchange reactions, we logarithms of initial relative rates (log(k /k )) against the corre-
2
X
H
12
2
extended the Fe(III)-catalyzed bromide–chloride exchange reaction to sponding s constants shows a good correlation (R = 0.9730), and
heteroaryl and polycyclic aromatic bromides, which are important the slope of the linear plot gives a r value of À1.16 (Fig. S8, ESI†). This
6,7b
but have only a few examples reported.
As expected (Table 2), r value confirms that the reaction is sensitive to substituents and
all the tested bromides, including thiophenes (3b, 3c), quinolines positive charge accumulation is evolved during the exchange reaction.
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Table 2 FeCl
chloride exchange reactions
3
-catalyzed heteroaryl and polycyclic aromatic bromide– with the release of a bromide free radical. The reaction between the
a
ꢀ
formed Br and the Fe(II) led to the regeneration of Fe(III) and the
formation of bromine ions in the end.
Time
(h)
Conv.
(%)
Select.
(%)
Entry
Substrate 3
Product 4
Moreover, it is interesting to observe that O is able to enhance
2
the conversion of bromobenzene greatly, while no oxidized Br
species is detected (Fig. S3 and S4, ESI†). This observation means
1
2
4
4
46.9
72.8
96.2
82.4
that the O
electrons in overall reaction. One plausible explanation is that O
can react rapidly with the formed Fe(II), which leads to the regenera-
2
can accelerate the reaction without gain or loss of
2
3
4
4
4
76.8
68.7
88.5
98.8
À
ꢀ
tion of Fe(III) and the formation of O
2
(Fig. S11, ESI†). The formed
À
ꢀ
O2 in the aprotic acetonitrile is rather stable, and can react with
the released Br to form Br and O . Thus, the cycle of Fe(II)/Fe(III),
ꢀ
À
2
5
4
63.6
85.4
and consequently the overall reaction are accelerated (pathway II, red
cycle in Scheme 2). However, substituents of bromobenzene with
labile hydrogen can release some protons upon reaction with the Cl .
ꢀ
6
7
4
4
72.4
73.6
94.7
86.1
Even a small amount of protons can largely enhance the reaction
À
ꢀ
with the formed O
2
to generate more active oxygen species such as
ꢀ
a
OH. This should be the reason for the lower selectivity of these
Reaction conditions: the same as those for the typical procedure
mentioned in Table 1.
reactions in an air atmosphere than in the O -free atmosphere.
2
In conclusion, an iron(III)-mediated photocatalytic method was
To clarify the halogen exchange mechanism, the Fe-catalyzed developed successfully to convert aryl, heteroaryl and polycyclic
exchange reactions of different aryl halogens with halide salts were aromatic bromides to the corresponding chlorides with high selec-
examined (Table S3, ESI†). It is observed that only the chlorine can tivity. The novel reactions occur under mild conditions without the
exchange the bromine and iodine on bromobenzene and iodo- assistance of other complex ligands. Moreover, the photocatalytic
À
benzene, respectively, to form chlorobenzene, which suggests that system exhibits very high Cl utilization efficiency. The employment
3
Àx
the [FeCl
The chlorine atom which originates from oxidation of the chloride makes it meaningful in green chemistry and photochemistry.
ion by photoinduced ligand to metal charge transfer (LMCT) of the
The financial support of this work from the 973 project (No.
x
]
complexes may play an important role in the reaction. of non-toxic iron salts combined with the use of light irradiation
complexes should be responsible for the chlorination reaction. There 2010CB933503, 2013CB632405), NSFC (No. 21137004, 21273245,
ꢀ
are several lines of evidence to support this Cl -initiated pathway. 21277147) and the CAS is gratefully acknowledged.
1
3
(
1) The Fe-based photochemical formation of radicals has
ꢀ
been extensively investigated. (2) The Cl has been applied to Notes and references
14
exchange the bromide on bromobenzenes. (3) The formation of
1
(a) J. Magano and J. R. Dunetz, Chem. Rev., 2011, 111, 2177;
b) G. C. Fu, Acc. Chem. Res., 2008, 41, 1555.
2 I. A. Cade and A. F. Hill, Organometallics, 2012, 31, 2112.
G. W. Gribble, Acc. Chem. Res., 1998, 31, 141.
T. D. Sheppard, Org. Biomol. Chem., 2009, 7, 1043.
(a) R. Schmidt, A. Stolle and B. Ondruschka, Green Chem., 2012,
14, 1673; (b) Y. M. Lee, M. E. Moon, V. Vajpayee, V. D. Filimonov and
K. W. Chi, Tetrahedron, 2010, 66, 7418; (c) X. Q. Shen, A. M. Hyde
and S. L. Buchwald, J. Am. Chem. Soc., 2010, 132, 14076; (d) H. Wu
and J. Hynes, Jr., Org. Lett., 2010, 12, 1192.
1
,4-dichlorobenzene from the 4-nitro-bromobenzene is consistent
and the enhanced
reaction rate of the electron-donating substitution is also observed
(
ꢀ
14b,c
with the Cl initiated exchange reaction,
3
4
5
ꢀ
14a
À
in the Cl system. (4) By usage of strong coordination agent F to
3Àx
decrease the formation of [FeCl
x
]
, the reaction is largely sup-
pressed (Fig. S10, ESI†). Accordingly, a proposed mechanism for the
Fe(III)-catalyzed bromide–chloride exchange reaction is shown in
Scheme 2. In the oxygen-free systems (pathway I, green cycle) after
complexes, Fe(II) and chlorine
free radicals are generated. Following the addition of the formed Cl
6 (a) W. B. Hardy and R. B. Fortenbaugh, J. Am. Chem. Soc., 1958,
0, 1716; (b) S. J. Lee and W. Lin, J. Am. Chem. Soc., 2002, 124, 4554.
7
3Àx
8
the LMCT by excitation of [FeCl
x
]
(a) A. Casitas, M. Canta, M. Sola, M. Costas and X. Ribas, J. Am.
Chem. Soc., 2011, 133, 19386; (b) X. Feng, Y. Qu, Y. Han, X. Yu,
M. Bao and Y. Yamamoto, Chem. Commun., 2012, 48, 9468.
N. E. L. Riina and K. Arvela, Synlett, 2003, 1145.
ꢀ
14a
and the rearrangement, chlorobenzene is formed, concomitantly
8
9
C. Bolm, J. Legros, J. L. Paih and L. Zani, Chem. Rev., 2004, 104, 6217.
1
0 (a) M. Zhang, C. Chen, W. Ma and J. Zhao, Angew. Chem., Int. Ed.,
008, 47, 9730; (b) G. Palmisano, E. Garcia-Lopez, G. Marci,
2
V. Loddo, S. Yurdakal, V. Augugliaro and L. Palmisano, Chem.
Commun., 2010, 46, 7074; (c) D. Ravelli, M. Fagnoni and A. Albini,
Chem. Soc. Rev., 2013, 42, 97.
1 (a) Z. Wang, X. Chen, H. Ji, W. Ma, C. Chen and J. Zhao, Environ. Sci.
Technol., 2010, 44, 263; (b) W. Ma, J. Li, X. Tao, J. He, Y. Xu, J. C. Yu
and J. Zhao, Angew. Chem., Int. Ed., 2003, 42, 1029.
1
1
1
1
2 C. Hansch, A. Leo and R. W. Taft, Chem. Rev., 1991, 97, 165.
3 V. A. Nadtochenko and J. Kiwi, Inorg. Chem., 1998, 37, 5233.
4 (a) B. Miller and C. Walling, J. Am. Chem. Soc., 1957, 79, 4187;
(b) K. Tanemura, T. Suzuki, Y. Nishida and T. Horaguchi, Tetrahedron,
Scheme 2 The proposed mechanism of iron(III)-mediated photocatalytic
bromide–chloride exchange reaction.
2010, 66, 2881; (c) C. R. Everly and J. G. Traynham, J. Am. Chem. Soc.,
1978, 100, 4316.
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