[emim]BF4-promoted chloromethylation of aromatic hydrocarbons

Article abstract of DOI:10.1080/00397910600775267

The chloromethylation of aromatic hydrocarbons proceeded efficiently using the reusable ionic liquid [emim]BF₄ as promoter. The reactions were completed in 5 h at 70°C with good yields and easy workup. Copyright Taylor & Francis Group, LLC.

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[emim]BF4‐Promoted Chloromethylation of
Aromatic Hydrocarbons
Yun Wang a , Zhi‐Cai Shang a & Tian‐Xing Wu a
a Department of Chemistry, Zhejiang University, Hangzhou, China
Published online: 16 Feb 2007.
To cite this article: Yun Wang , ZhiCai Shang & TianXing Wu (2006) [emim]BF4‐Promoted Chloromethylation
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Synthetic Organic Chemistry, 36:20, 3053-3059, DOI: 10.1080/00397910600775267
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Synthetic Communicationsw, 36: 3053–3059, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600775267
[emim]BF4-Promoted Chloromethylation of
Aromatic Hydrocarbons
Yun Wang, Zhi-Cai Shang, and Tian-Xing Wu
Department of Chemistry, Zhejiang University, Hangzhou, China
Abstract: The chloromethylation of aromatic hydrocarbons proceeded efficiently
using the reusable ionic liquid [emim]BF4 as promoter. The reactions were
completed in 5 h at 708C with good yields and easy workup.
Keywords: Aromatic hydrocarbons, chloromethylation, ionic liquid [emim]BF4
INTRODUCTION
Chloromethyl-substituted aromatic hydrocarbons are promising key inter-
mediates because of their easy transformation to many chemicals such as
fine chemicals, pharmaceuticals, and polymers. The chloromethylation of
aromatic hydrocarbons has been documented in previous papers.[1–7] The
reaction of aromatic hydrocarbons with hydrochloric acid and trioxane or
paraformaldehyde as a formaldehyde precursor sometimes gave chloromethy-
lated products without catalyst;[6,7] however, the rate is slow and insufficient
for practical chemical process. Lewis acids such as zinc chloride, stannic
chloride, and boron trifluoride are well-known catalysts for the reaction;
among these acids, zinc chloride is an effective catalyst in hydrochloric acid
solution.[1,2] However, a stoichiometric amount of catalyst to substrate is
required, making the workup procedure tedious. These catalysts, in general,
suffer from the inherent problems of corrosiveness, high susceptibility to
water, difficulty in catalyst recovery, environmental hazards, and waste
control after the reaction. So, it is important to replace these highly
Received in R.O.C. February 27, 2006
Address correspondence to Zhi-Cai Shang, Department of Chemistry, Zhejiang
University, Hangzhou 310027, China. E-mail: shangzc@zju.edu.cn
3053

3054
Y. Wang, Z.-C. Shang, and T.-X. Wu
corrosive, hazardous, and polluting acid catalysts with environmentally
conscious catalysts that are active under mild conditions and can be easily
recovered after the reaction for reused.[8] Kishida et al. reported rare-earth
metal triflates are active catalysts for this reaction,[9] but the rare-earth
metal triflates are expensive and thus not suitable for industry.
Ionic liquids (ILs) are very attractive solvents because they have very low
vapor pressure and are stable in a wide temperature range.[10,11] Examples of
their application in both reactions[12] and separation[13] have been demon-
strated. Recently, ILs are attracting more attention because they are showing
a significant role in controlling the reactions as catalysts. A variety of ILs
are successfully applied in many types of reactions such as Friedel–Crafts
acylations[14] and alklations.[15] In this article, our research shows that the
IL 1-ethyl-3-methylimidazolium tetrafluoroborate ([emim]BF4) is highly
active for the chloromethylation of many aromatic hydrocarbons, and the
reaction was completed in short time with good yields and easy workup.
EXPERIMENTAL
The IL [emim]BF4 was prepared by the procedures given in the literature.[16]
All the other chemicals and reagents were of analytical grade and used as
obtained.
Instrumental Analysis and Measurements
Melting points were determined on digital melting-point apparatus and
1
are uncorrected H NMR spectra were recorded on a Bruker 500-MHz spec-
trometer using CDCl3 as the solvent with tetramethylsilane (TMS) as an
internal standard. GC-MS spectra were recorded on HP6890 gas chromato-
graph with a HP5973 mass spectrometric detector. High performance liquid
chromatography (HPLC) experiments were performed on a liquid chromato-
graph (Dionex Softron GmbH, America), consisting of a pump (P680) and
ultraviolet-visible light detector (UVD) system (170U). The experiments
were performed on Zirchrom ODS-1 column, f 4.6 ꢀ 250 mm.
General Experimental Procedure for the Chloromethylation of
Aromatic Hydrocarbons
All the three-necked flasks were loaded with aromatic hydrocarbon
(16.4 mmol), paraformaldehyde (36.3 mmol), concentrated hydrochloric
acid (16 mL), and IL [emim]BF4 (4.92 mmol). The reaction mixture was
stirred at 708C for an appropriate time. After the reaction, the mixture was
filtered and extracted with methylene chloride (3 ꢀ 20 mL). The organic

[emim]BF4-Promoted Chloromethylation of Aromatic Hydrocarbons
3055
phases were combined and rinsed with saturated NaHCO3 solution
(2 ꢀ 20 mL) and water (2 ꢀ 20 mL). The organic phase was dried with
sodium sulfate, filtered, and evaporated to dryness in vacuo, and the organic
residue was resolved in methylene chloride again and analyzed by HPLC.
Each product was separated by silica-gel column chromatography and ident-
1
ified by H NMR. Residual aqueous catalytic solution was evaporated in
vacuo to a colorless liquid in 93% yield. The next run was performed under
identical reaction conditions.
RESULTS AND DISCUSSION
The chloromethylation of m-xylene was initially tested at 708C in the presence
of [emim]BF4; the conversion of m-xylene was only 66% when 0.1 equiv
of [emim]BF4 was used as promoter (Table I, Entry 2). Fortunately, the
desired reaction was efficiently accomplished when the reaction was camed
out using 0.3 equiv of [emim]BF4 (Entry 3). The subsequent condition-
optimization experiments revealed that 5 h and 0.3 equiv of the promoter
were necessary to complete the reaction. When 4 h or 0.2 equiv of the
promoter was used, the conversion only reached 87% and 80%, respectively
(Entries 7 and 8). In addition, the IL could be typically recovered and
reused with no appreciable decrease in yields and reaction rates (Entries 4,
5). Some blank experiments were also carried out to demonstrate the
promotion of [emim]BF4. As shown in Table 1, when the reaction was
Table 1. [emim]BF4 as catalyst for the chloromethylation of
m-xylene at 708C
[emim]BF4
(equiv.)
Time
(h)
Conversion
(%)
A:B
(yield%)a,b
Entry
1
2
3
4
5
6
7
8
0
48
7
63
66
93
93
92
93
80
87
59:4
63:3
85:8
85:8
84:8
85:8
76:4
80:7
0.1
0.3
0.3c
0.3d
0.5
0.2
0.3
5
5
5
5
5
4
aA is 1,5-bis(chloromethyl)-2,4-dimethylbenzene; B is 1-chloro-
methyl-2.4-dimethylbenzene.
bA:B for each sample was determined by HPLC.
cThe second run.
dThe third run.

3056
Y. Wang, Z.-C. Shang, and T.-X. Wu
Scheme 1.
performed without [emim]BF4, the conversion only reached 63% after 2 days
(Entry 1) (Scheme 1).
With these results in hand, we subjected other aromatic hydrocarbons to
these optimized conditions, and the results are listed in Table 2. Various
aromatic hydrocarbons such as benzene, o-xylene, p-xylene, and methylphe-
nate were efficiently converted to the corresponding chloromethyl-substituted
aromatic hydrocarbons using a catalytic amount of [emim]BF4 at 708C. Yields
of these reactions are almost quantitative in most cases. Unfortunately, we did
not obtain satisfactory results when the same methods were applied to chloro-
benzene, brombenzene, and nitrobenzene.
SPECTROSCOPIC DATA FOR SELECTED PRODUCTS
1,5-bis(Chloromethyl)-2,4-dimethylbenzene: Mp 1018C; 1H NMR (500 MHz,
CDCl3) d 7.26 (s, H, ArH), 7.05 (s, H, ArH), 4.58 (s, 4H, 2CH2Cl), 2.39 (s, 6H,
2CH3); GC-MS: 202, 167, 131, 115, 91, 77.
1
1-Chloromethyl-2,4-dimethylbenzene: H NMR (500 MHz, CDCl3) d 7.20
(s, 1H, ArH), 7.00 (s, 2H, AH), 4.56 (s, 2H, CH2Cl), 2.37 (s, 3H, CH3),
2.30 (s, 3H, CH3); GC-MS: m/z ¼ 154 (Mþ), 119, 115, 103, 91, 77.
1,4-bis(Chloromethyl)-2,5-dimethylbenzene: Mp 1308C; 1H NMR (500 MHz,
CDCl3) d 7.14 (s, 2H, ArH), 4.55 (s, 4H, CH2Cl), 2.37 (s, 6H, 2CH3); GC-MS:
202, 167, 131, 115, 91, 77.
1
1-Methoxyl-2,4-bis(chloromethyl)benzene: Mp 53–548C; H NMR (500 MHz,
CDCl3) d 7.39–7.40 (d, J ¼ 5 Hz, 1H, ArH), 7.32–7.34 (q, 1H, ArH),
6.86–6.88 (d, J ¼ 10 Hz, 1H, ArH), 4.64 (s, 2H, CH2Cl), 4.59 (s, 2H,
CH2Cl), 3.88 (s, 3H, OCH3); GC-MS: 204, 169, 139, 103, 91, 77.
1
1-Chloromethyl-2,5-dimethylbenzene: H NMR (500 MHz, CDCl3) d 7.21
(s, 1H, ArH), 7.17 (s, IH, ArH), 4.65 (s, 2H, CH2Cl), 2.47 (s, 3H, CH3),
2.40 (s, 3H, CH3); GC-MS: m/z ¼ 154(Mþ), 119, 115, 103, 91, 77.
1,2-bis(Chloromethyl)-4,5-dimethylbenzene: Mp 1068C; 1H NMR (500 MHz,
CDCl3) d 7.17 (s, 2H, ArH), 4.73 (s, 4H, 2CH2Cl), 2.28 (s, 6H, 2CH3); GC-
MS: 202, 167, 132, 115, 91, 77.

Table 2. [emim][BF4] as catalyst for the chloromethylation of aromatic hydrocarbons at 708C
Aromatic
hydrocarbon
[emim][BF4]
(equiv.)
Time
(h)
Conv.
(%)a
Entry
1
Products and yields (%)b
0.3
0.3
5
5
76
97
2
3
0.3
0.3
5
5
91
90
4
5
6
0.3
1.0
5
93
0
48
—
aIsolated conversion.
bYields for each sample were determined by HPLC.

3058
Y. Wang, Z.-C. Shang, and T.-X. Wu
CONCLUSION
In summary, IL [emim]BF4 has been proven to be an effective promoter for
the chloromethylation of aromatic hydrocarbons. The present method has
many obvious advantages compared to previous methods, such as being
environmentally more benign, easy product isolation, simple methodology,
the high yield, generality, convenience of preparing IL [emim]BF4 using
much cheaper starting material, and potential for recycling the IL. We have
shown that IL [emim]BF4 can replace other catalysts and is a simple
system—a good example of green chemistry.
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