Nucleophilic substitution of hydrogen in naphthalene by chloride (Cl -) in ionic liquids

Article abstract of DOI:10.1016/j.cclet.2010.09.021

Nucleophilic aromatic substitution of hydrogen in non-activated aromatic ring, a very rare phenomenon in organic chemistry, is found in ionic liquids containing Cl^- as anion under mild reaction conditions. The reaction may be carried out by the addition of the halogen-bonding adduct (Br ₂Cl^-) as nucleophile to aromatic ring carbon atom, leading to the formation of the nucleophilic substitution product.

Full text of DOI:10.1016/j.cclet.2010.09.021

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 147–150
www.elsevier.com/locate/cclet
Nucleophilic substitution of hydrogen in naphthalene
by chloride (Clꢀ) in ionic liquids
*
Shen Yi Shi, Ai Guo Kong, Xin Hua Zhao, Han Ming Ding, Fan Yang, Yong Kui Shan
Department of Chemistry, East China Normal University, Shanghai 200062, China
Received 22 April 2010
Abstract
Nucleophilic aromatic substitution of hydrogen in non-activated aromatic ring, a very rare phenomenon in organic chemistry, is
found in ionic liquids containing Clꢀ as anion under mild reaction conditions. The reaction may be carried out by the addition of the
halogen-bonding adduct (Br2Clꢀ) as nucleophile to aromatic ring carbon atom, leading to the formation of the nucleophilic
substitution product.
# 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
Keywords: Ionic liquid; Aromatic compound; Naphthalene; Nucleophilic reaction; Halogen bonding
Nucleophilic aromatic substitution of hydrogen in carbo- and heteroaromatic systems is a subject of considerable
interest to chemists. The nucleophilic substitution reaction is only favored by electron withdrawing substituents on the
aromatic ring in order to decrease p-electron density and facilitate approach of a nucleophile. The nucleophilic
aromatics substitution of hydrogen in the non-activated (unsubstituted) aromatic ring is very rarely observed. Up to
now, only two examples completed under the extremely overcritical conditions have been known [1,2] However, a
very more surprising phenomenon was observed in our experiment, in which anionic Clꢀ replaces hydrogen in the
non-activated naphthalene in the bromination reaction of naphthalene with bromine while the ionic liquid containing
Clꢀ as anions was used as reactive medium, and the selectivity of chloronaphthalene reach up to 87% based on
naphthalene. In order to explore and understand these chemical processes, the chemical behavior of bromonaphthalene
was examined in detail in the ionic liquid containing Clꢀ as anions. The result shows that no nucleophilic substitution
of bromonaphthalene with Clꢀ as prediction occurs in this system.
Negatively charged halogen atoms are capable of forming donor–acceptor bonds with halogen molecules to create
the halogen-bonded prereactive complexes (halogen-bonded adducts) [3]. When Br2 was dissolved in the ionic liquid
containing Clꢀ as anions, anion prereactive complexes [Cl–Br–Br]ꢀ may be formed, and in which mid part bears some
positive electric charge and each end of which is electronegative due to the induced polarization of anion Clꢀ shown as
following: {Cldꢀ–Brd+–Brdꢀ}. Addition of this prereactive complex as nucleophile to naphthalene ring carbon atom
lead to the formation of the nucleophilic substitution products (Scheme 1).
* Corresponding author.
E-mail address: ykshan@chem.ecnu.edu.cn (Y.K. Shan).
1001-8417/$ – see front matter # 2010 Published by Elsevier B.V. on behalf of Chinese Chemical Society.
doi:10.1016/j.cclet.2010.09.021

[()TD$FIG]
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S.Y. Shi et al. / Chinese Chemical Letters 22 (2011) 147–150
Clδ− - Brδ+ -Brδ−
Cl
Clδ− - Brδ+ -Brδ−
-
-
Br
HBr
Scheme 1. Diagrammatic sketch of the reaction process of naphthalene with R[Br2Cl] (R = [BPy] (1-n-butylpyridinium), [Bmim] (1-n-butyl-3-
methyl imidazolium), etc.)).
Support to the proposed reactions pathway of Scheme 1 come from the experimental results for halogenation of
naphthalene at different reaction times and in different molar ratios of bromine and [BPy][Cl]. The experimental data
exhibit an increase in selectivity of chloronaphthalene on going from the higher amount of the added Br2 to the lower
and suggest the occurrence of the reactive equilibrium in this ionic liquid system as follows (Eq. (1)):
Clꢀ þ Br2 $ Br2Clꢀ
(1)
In the equilibrium, the higher amount of Br2 do not alone promote the formation of the more Br2Clꢀ, and also
increase the equilibrium concentration of the electrophilic reagent Br2 leading to the formation of bromonaphthalene
and the decreasing the selectivity of chloronaphthalene at the Clꢀ amount as the constant. The substitution reactions of
Br2Clꢀ or Br2 with naphthalene to give chloronaphthalene or bromonaphthalene were represented by the following
equation:
Br2Clꢀ þ naph $ naphꢀCl þ HBr þ Brꢀ
(2)
Br2 þ naph $ naphꢀBr þ HBr
(3)
The reactions in Eqs. (1) and (2) possess a character of the consecutive reactions and those in Eqs. (2) and (3)
display a behavior of the parallel reactions. In the course of reaction, the selectivity for the dominant nucleophilic
chlorization of naphthalene in the system decreases as the reactive time increase owing to the occurrence of the
electrophilic bromination and gradually approaches the value of the equilibrium state. The selectivity for 1-
chloronaphthalene can reach 87% in the mixture of naphthalene (0.5 mmol), Br2 (0.5 mmol) and [BPy][Cl] (10 mmol)
at 100 8C under reflux for 10 min.
In order to deeply comprehend the nature of the interspecies interactions and further illustrate reaction procedure in
this system, a series of the aromatic substituent experiments were devised. The results were shown in Tables 1 and 2. In
Table 1
Halogenation of naphthalene in different mediaa.
Entry
Medium (10 mmol)
Con. (mol%)b
Sel. (mol%)b
Naph–Cl
Naph–Br
Otherse
1
2
3
4
5
6
7
8
9
[BPy][Cl]
[HPy][Cl]
[DPy][Cl]
[4-MeBPy][Cl]
[Bmim][Cl]
HClc
65%
65%
66%
54%
75%
82%
79%
87%
80%
81%
19%
22%
24%
34%
52%
93%
84%
92%
90%
–
78%
–
76%
–
66%
–
48%
–
4%
3%
15%
8%
10%
d
ZnCl2
<1%
<0.2%
<0.2%
d
FeCl3
d
AlCl3
a
Reaction conditions: naphthalene (1 mmol), Br2 (1 mmol) and medium (10 mmol); reaction temperature 100 8C; reaction time 4 h under reflux.
Conversion and selectivity were determined by GC based on naphthalene.
1.0 g 37% HCl aqueous solution, reaction temperature: 40 8C.
2.0 g saturated metal chloride aqueous solution, reaction temperature: 40 8C.
Other product is dibromonaphthalene.
b
c
d
e

S.Y. Shi et al. / Chinese Chemical Letters 22 (2011) 147–150
149
Table 2
Halogenation of different aromatics in [BPy][Cl] ionic liquid.a
Entry
Substrate
Con. (mol%)b
Sel (mol%)b
Monochloride
Cl
Monobromide
1
0%
0%
0%
Br
0%
[TD$INLINE]
[DT$INLE]
[DT$INLE]
2
3
92%
95%
100%
[TD$INLINE]
[DT$INLE]
[DT$INLE]
Cl
OMe
Br
OMe
0%
100%
19%
OMe
[DT$INLE]
[DT$INLE]
[TD$INLINE]
Cl
Br
Br
Cl
4
65%
81%
[DT$INLE]
[DT$INLE]
[TD$INLINE]
5
6
85%
93%
22%
8%
78%
92%
E
Cl
[TD$INLE]
Br
[TD$INLINE]
OH
OH
Br
OH
Cl
[
[TD$INLE]
Br
Br
Br
7
65%
69%
65%
70%
35%
30%
]
[TD$INLE]
[TD$INLINE]
Cl
Br
Br
Cl
8
[DT$INLE]
[DT$INLE]
[TD$INLINE]
a
Reaction conditions: 1 mmol substrate, 1 mmol Br2 and 10 mmol [BPy][Cl]; reaction temperature 100 8C; reaction time 4 h under reflux.
Conversion and selectivity were determined by GC or HPLC based on substrate.
b
all of the experimental results shown in Table 1, the selectivity of the chloronaphthalene in the ionic liquids are the very
much higher than those in the analogous inorganic salt solutions and highest selectivity (81%) of the
chloronaphthalene appears in the ionic liquid [BPy][Cl] (1-n-butylpyridinium chloride) under identical conditions.
This phenomenon may be attributed to the charge-diffuse Br2Clꢀ having the much higher stability in ionic liquids than
in the analogous inorganic salt solutions [4] and the ionic liquid cation exerting the hydrogen bonding donor ability on
the leaving Brꢀ anion in the rate-determining step [5]. Of cause, the solvent dependency in nucleophilic substitution
can be interpreted with reference to the nature of the charge distributions in the ground state and the activated complex
in the rate-determining step [6]. It is worthy of note that the ionic liquids with different cation structures exhibit
different abilities to affect the selectivity of the chloronaphthalene (Table 1, entries 1ꢀ5). This feature is in agreement
with the recently reported data about nucleophilic substitution reactions in ionic liquids [5,7]. The longer or more alkyl
chains on the ring of pyridine make the ionic liquid more viscous [8] and give rise to the lower selectivity of
chloronaphthalene as shown in Table 1, entries 1ꢀ4. The experimental results in Table 2 clearly testify a fact that the
effects inducing the increase of electron density on the aromatic ring always produce the lower selectivity of
chloronaphthalene. Under the same conditions in this ionic liquid system, the selectivity of nucleophilic substitution of
the aromatic hydrogen by Clꢀ decrease on going from the feebler (Table 2, entry 7, 65%) to the stronger (Table 2, entry
6, 8%) electron releasing group located on the naphthalene ring, whenas the nucleophilic substitution reaction of

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S.Y. Shi et al. / Chinese Chemical Letters 22 (2011) 147–150
aromatic hydrogen of benzene or its derivatives bearing electron releasing group with Clꢀ do not occur. It further
verifies that the replacement of aromatic hydrogen follows the fundamental principles of nucleophilic substitution in
this ionic liquid system. Detailed reaction mechanism is in progress in our lab.
1. Experimental
[Bmim][Cl] (1-n-butyl-3-methylimidazolium chloride), [BPy][Cl] (1-n-butylpyridinium chloride), [HPy][Cl]
(1-n-hexylpyridinium chloride), [DPy][Cl] (1-n-decyl-pyridinium chloride), [4-MeBPy][Cl] (4-methyl-1-n-butyl-
pyridinium chloride) ionic liquids were synthesized according to the procedures reported previously respectively [9].
The typical reaction procedures of halogenation of aromatics are as follows: bromine (1 mmol, 0.160 g) and
[BPy][Cl] (10 mmol, 1.72 g) ionic liquid were added in a 50 mL three-necked flask and stirred vigorously for 30 min
at 100 8C in the N2 atmosphere, and [BPy][Br2Cl] was obtained. After that, naphthalene (1 mmol, 0.128 g) was added
and further heated at 100 8C for 4 h under stirring. Finally, the reaction was stopped and cooled to room temperature.
The products were extracted by diethyl ether (three times, 5 mL each) and quantitatively analyzed by GC using toluene
as the internal standard substance. All products were determined by MS or GC–MS and FTIR.
Apparatus and instruments used for identification of the products. IR: NEXUS 670-FTIR infrared spectrometer;
HPLC: Varian Pro Star 210 (Agilent XDB-C18 column); GC: Shimadzu GC-14C (Agilent DB-1 30 m, 0.25 mm); GC-
MS: CP-3900GC/Saturn 2100MS system.
Acknowledgments
We thank the key project of Shanghai Science and Technology Committee (Nos. 05JC14070, 06DZ05025,
08JC1408600) for financial supports.
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