Catalytic dechlorination of aromatic chlorides using Grignard reagents in the
presence of (C5H5)2TiCl2
Ryuichiro Hara, Kimihiko Sato, Wen-Hua Sun and Tamotsu Takahashi*
Catalysis Research Center and Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo
060-0811, Japan and CREST, Science and Technology Corporation (JST), Sapporo 060-0811, Japan.
E-mail: tamotsu@cat.hokudai.ac.jp
Received (in Cambridge, UK) 3rd March 1999, Accepted 30th March 1999
Dechlorination of aromatic chlorides was efficiently per-
formed with alkyl Grignard reagents in the presence of a
catalytic amount of (C5H5)2TiCl2.
4-chlorophenol was deprotonated by an additional equimolar
amount of Grignard reagent and the reaction then proceeded
(entry 7).
When 2,4-dichloroanisole was treated with a catalytic
amount of (C5H5)2TiCl2 (0.2 mmol) and 6 equiv. of BuMgCl,
the 2,4-dichloroanisole was completely consumed within 1 h.
Anisole was obtained in 66% yield after 24 h, and 24% of
4-chloroanisole and 10% of 2-chloroanisole remained. Addition
of 9 equiv. of BuMgCl did not significantly improve this
situation.
Dehalogenation of organic halides is a fundamental subject in
organic chemistry.1 Therefore, diverse methods and a variety of
reagents have been developed. The reactivity order of halogens
is, in most cases, I > Br > Cl 9 F, and that of halogen-
containing substrates is allylic ≈ benzylic > aliphatic >
aromatic. It is thus suggested that dechlorination of aromatic
chlorides cannot readily be achieved,2 and the development of
methodology for such remains to be studied. In addition to the
synthetic usefulness of the reaction, recently evolving eco-
logical demands for dechlorination of pollutant perchlorinated
compounds3 strongly motivated us toward this subject.4
We have recently published a report that (C5H5)2ZrCl2
catalyzed the efficient and selective debromination or deiodina-
tion reactions of aromatic halides using alkylmagnesium
reagents.5 However, this reaction did not proceed at a
significant level for chloro derivatives. During the course of our
study on the dechlorination reactions of aromatic chlorides, we
found that titanocene dichloride catalyzed the reduction of
aromatic chlorides when used with appropriate alkylmagnesium
reagents [eqn. (1)].
Interestingly, when a combination of 1.0 equiv. of
(C5H5)2TiCl2 and 2.0 equiv. of BuMgCl was used for the
Table 1 Assessment of Grignard reagents and solvents in the (C5H5)2TiCl2-
catalyzed dechlorination of 4-chloroanisolea
RMgX, (C5H5)2TiCl2 (10 mol%)
MeO
Cl
MeO
H
room temp.
Recovered
p-chloroanisole
(%)b
Entry
RMgX
Solvent Yield (%)b
1
2
3
4
5
6
7
8
9
MeMgBr
EtMgBr
PrMgBr
PriMgBr
BuMgCl
BuMgCl
BuMgCl
BuiMgBr
ButMgBr
THF
THF
THF
THF
THF
Et2O
hexane
THF
THF
0
59
91
93
95
59
53
42
81
83
5
100
34
5
0
0
35
38
52
17
15
90
RMgBr, Cp2TiCl2 (cat.)
Ar Cl
Ar
H
(1)
THF, room temp.
Colomer and Corriu reported early in 1974 that PriMgBr–
(C5H5)2TiCl2 reacted with various organic bromides and
iodides in Et2O to give the dehalogenated products.6 They
suggested, however, that their system was not applicable to
aromatic chlorides.
The use of THF as a solvent was found to dramatically
improve the reactivity of the titanium-catalyzed dehalogenation
reaction. A typical reaction procedure is as follows: To a
solution of an aromatic chloride (1.0 mmol) and (C5H5)2TiCl2
(0.1 mmol, 0.1 equiv. with respect to the substrate) in THF (2.5
ml) was added BuMgCl (1.0 M solution in THF, 3.0 mmol, 3
equiv. at 278 °C. The reaction mixture was stirred at ambient
temperature for several hours and the products were detected by
GC and NMR.
10
11
a
Isopentyl MgBr THF
Neopentyl MgBr THF
The typical reaction conditions: 4-chloroanisole (1 mmol), alkylmagne-
sium reagent (3 mmol), (C5H5)2TiCl2 (0.1 mmol), room temperature, 48 h.
b Yields were determined by GC.
Table 2 Results of (C5H5)2TiCl2-catalyzed dechlorination reactiona
Recovered
Aromatic
chloride
aromatic
chlorides (%)b
Entry
t/h
Yield (%)b
Dechlorination of 4-chloroanisole was carried out using
various Grignard reagents (Table 1). As expected, MeMgBr did
not reduce 4-chloroanisole. The reaction with PhMgBr, which
has an aromatic b-hydrogen, did not proceed. ButCH2MgBr
which has g- rather than b-hydrogens, gave a yield which did
not exceed the amount of catalyst used. The reaction with
ButMgBr or EtMgBr gave moderate yields while the reactions
with PrMgBr, PriMgBr, BuiMgBr or BuMgCl gave high yields.
Thus, the difference in reactivity may be due to both the b- and
g-hydrogens and their steric factors.
1
2
3
4
5
6
7d
8e
a
PhCl
48
6
48
48
74c
99
80
12
0
12
0
0
0
2-Chloroanisole
3-Chloroanisole
4-Chloroanisole
1-Chloronaphthalene 0.5
2-Chloronaphthalene 0.5
95
> 99
> 99
4-Chlorophenol
2,4-Dichloroanisole 24
3
> 99c
0
f
f
The typical reaction conditions: BuMgCl (3 equiv.), (C5H5)2TiCl2 (0.1
b
equiv.), room temperature. Unless otherwise noted, yields were deter-
mined by GC. Yield was determined by NMR. BuMgCl (4 equiv.).
e BuMgCl (6 equiv.), (C5H5)2TiCl2 (0.2 equiv.). Yield of anisole: 66%;
Table 2 shows the results of dechlorination of various
aromatic chlorides. Chloroanisoles were reduced to anisole over
varied reaction times (entries 2–4). Chloronaphthalenes were
reduced within 30 min (entries 5 and 6). The hydroxy group of
c
d
f
2-ClC6H4OMe: 10%; 4-ClC6H4OMe: 24%; 2,4-Cl2C6H3OMe: 0%.
Chem. Commun., 1999, 845–846
845