International Journal of Organic Chemistry, 2011, 1, 176-182
doi:10.4236/ijoc.2011.14026 Published Online December 2011 (http://www.SciRP.org/journal/ijoc)
BF3·OEt2-Mediated Benzylation of Arenes and
Heteroarenes with Benzyl Ether Derivatives
Ling Dang, Qiang Li, Tongmei Ma*, Sheng Sheng, Wei Zeng*
School of Chemistry and Chemical Engineering, South China University of Technology , Guangzhou, China
Received October 18, 2011; revised November 26, 2011; accepted December 3, 2011
Abstract
An efficient BF3·Et2O-promoted benzylation of arenes and heteroarenes with various benzyl ether derivatives
has been developed. This method provided alternative access to valuable diarylmethane in good yields under
mild conditions via an easy work-up procedure.
Keywords: Friedel-Crafts Alkylation, BF3·Et2O, Diarylmethane, Benzyl Ether Derivatives, Arenes
1. Introduction
Diarylmethane motifs are an important class of aromatic
building blocks which are found in various biologically
active compounds such as anastrozole, papaverine, piri-
trexim, avrainvilleol, and beclobrate [1-5]. They are also
used as key precursors in the synthesis of electroactive
and photoactive oligomers and polymers [6,7]. Consequ-
ently, various methodologies for the alkylation of arenes
and heteroarenes have been developed [8-10]. Among
the various functionalization reactions of arenes, Friedel-
Crafts alkylation (FCA) provides an efficient access to
building a diarylmethane framwork via the electrophilic
addition of cationic species to aromatic compounds.
Previous work about FCA has mainly centred on using
alcohols [11-14], benzyl halides [15-18], aldehyde [19-
21], carboxylic acid ester [22,23] or alkenes [24-26] as
the alkylating agents in the presence of kinds of Brønsted
acids, Lewis acids and transition metal salts [11-26], but
there have not been many trials for the development of
FCA with ethers as electrophilics possibly due to the
stable ether bond. Nevertheless, recently Peris and Shiina
group, etc. demonstrated that Ir-NHC complexes, SiCl4/
AgOTf and Hf(OTf)4 et al. could efficiently catalyze alk-
yaltion of arenes using ethers as alkyalting agents succes-
sively [24,27-30]. Considering the wide application of dia-
rylmethane derivatives in the synthesis of biological mo-
lecules, the exploration of more economic catalysts for al-
kylation of arenes with ethers under mild conditions is de-
sirable.
Recently, we have focused our attention on Lewis acid-
catalyzed N-alkylation of sulfonamides using unactive
ethers as alkyalting agents. During the period that we
investigated the effect of various Lewis acids on the N-
alkylation of 4-toluene sulfonamide 5 in toluene solvent,
we found BF3·Et2O could enhance the formation of by-
product diarylmethane 3a and 4a (around 10% yield)
from the alkyaltion of toluene 2a and benzyl ether 1a
(see Scheme 1), and further studies indicated that bypro-
duct diarylmethane 3a and 4a did not form in the pres-
ence of other Lewis acids including AlCl3, TiCl4, Cu-
(OAc)2·2H2O, CdCl2·2.5H2O, ZrCl4, MgO, etc. Herein, we
reported our further studies about BF3·Et2O-promoted
benzylation of arenes with benzyl ether derivatives.
2. Results and Discussions
Initially, the alkylation of toluene with dibenzyl ether was
employed as a model reaction, optimization studies were
carried out under different conditions, and the correspon-
ding results were summarized in Table 1. As shown in
Table 1, when the FCA of toulene (6.0 equiv.) with di-
benzyl ether (0.5 mmol) was carried out using BF3·Et2O
(3.0 equiv.) as promoter under refluxing condition in
Scheme 1. Lewis acid-poromoted N-alkylation of sulfonami-
de and alkylation of toluene.

177 L. DANG ET AL.
Table 1. Reaction conditions optimized for Friedel-Crafts
benzylation of toluene.
O+CH
3
BF
3
.Et
2
O
solvent
CH
3
CH
3
reflux +
1a 2a 3a 4a
entry toluene
(equiv) solvent reaction time (h)
reaction
temp. (˚C)
yieldb
(%)
1 3 DMF 24 110 --
2 3 DMSO 24 150 --
3 3 CCl4 24 85 <10
4 3 CH3CO2Et 24 77 31
5 3 Acetone 24 56 18
6 3 CH3CN 24 85 28
7 3 CHCl3 24 65 52
8 3 dioxane 24 110 68
9 3 TCEc 24 110 48
10 6 dioxane 24 110 75
11 8 dioxane 24 110 64
12 6 dioxane 24 90 57
13 6 dioxane 48 110 65
14 6 dioxane 24 140 63
15 6 dioxane 24 110 69d
16 6 dioxane 24 110 72e
aUnless otherwise noted, all the reactions were carried out under Ar atmos-
phere in sealed tube, benzyl ethers (0.5 mmol), BF3·Et2O (3.0 equiv), sol-
vent (1.5 mL); b Isolated yield of isomers (3a and 4a); cTCE: 1, 1, 2,
2-tetrachloroethane; d2.0 equiv of BF3.Et2O was used; e5.0 equiv of BF3·Et2O
was used.
different solvents (1.5 mL) for 24 h, we found the nature
of solvents had significant effect on this transformation
(entries 1 - 9), among the solvents examined, 1,4-dioxane
gave the best result (68% yield) (entry 8). The further op-
timized results indicated that the suitable substrate ratio
(2a/1a = 12) could lead to the best yield (75%) (compare
entries 8, 10 and11), and lowering the reaction tempera-
ture to 90˚C or increasing to 140˚C resulted in a decrea-
sed yield due to incomplete reaction or tedious work-up,
respectively (compare entries 10, 12 and 14). Finally, we
investigated the effect of BF3·Et2O loading on the trans-
formation, and found a decreased yield of diarylmethane
was obtained at low promoter loading (2.0 equiv.) (com-
pare entries 10 and 15), but higher promoter loading (5.0
equiv.) did not increase the yield of desired compound
any further (compare etnries 10 and 16).
With the optimized parameters in hand, we tested the
general applicability of the BF3·Et2O-promoted FCA of
arene with dibenzyl ether, by varying both the ether and
the arene/heteroarene. As shown in Table 2, the benzyl
ether alkylating reagents examined could be performed
smoothly in moderate to good yields. Analysis of the ef-
ficiency about this transformation indicates that electro-
nic effect gorven the FCA system. The alkyaltion of di-
benzyl ether with electron-rich aromatic compounds con-
taining methyl, methoxy or hydroxyl group could occur
Table 2. BF3·OEt2-mediated Friedel-Crafts benzylation of different aromatic compound with benzyl ether derivativesa.
entry ethers arenes productb yieldc (%)/(ratio: o/p)
1
O
1a
Me
2a
M
e
3a
Me
4a
74 (3:5)
2
O
1a
Me
Me
2b
Me
3b
Me
4b
Me
Me
73 (2:5)
3
O
1a
Me
2c
Me
M
e
3c
Me
4c
Me
Me
80 (1:5)
4
O
1a
2d
Me
Me
Me
3d
Me
71
5
O
1a
2e
Me Me
Me
3e
Me Me
Me
78

L. DANG ET AL.
178
6
O
1a
O
Me
2f
3f
O
4d
OMe
Me
49(1:5)
7
O
1a
Cl
2g
3g
Cl
4e
Cl
0
8
O
1a
NO
2
2h
3h
NO
2
0
9
O
1a
2i
3i 4
f
78 (4:1)
10
O
1a
OH
2
j
OH
3
j
49
11
O
1a
S2k
SS
3k 4
g
73 (2:1)
12
O
1a
O2l
OO
3l 4h
17d (10:1)
13
OMe
1b
Me
2a
M
e
3a
Me
4a
68 (3:5)
14
O
1c
Me
Me
2a
M
e
3a
Me
4a
66 (3:5)
15
O
1d Me Me
Me
2a
M
e
3m
Me
4i
Me
Me
68 (3:5)
16
O
1e Cl Cl
Me
2a
M
e
3n
Me
4j
Cl
Cl
76 (7:10)
17
O
1f
O
2
NNO
2
Me
2a
Me
3o
Me
4k
O
2
N
O
2
N
53e (7:10)
aUnless otherwise noted, all reactions were carried out in sealed tube at 110˚C under Ar atmosphere for 24 h, benzyl ethers (0.5 mmol), arenes (12.0 equiv),
BF3.Et2O (3.0 equiv), 1, 4-dioxane used as solvent (1.5 mL ); bAll products are known compounds and identified using 1H NMR, LR-MS and IR; cIsolated yield
and the ratio of the isomers were determined by 1H NMR; d Reaction temp.: 60˚C, reaction time: 36 h; e Reactiom temp.: 150˚C, reaction time: 42 h.

L. DANG ET AL.
179
efficiently to afford diarylmethan in moderate to good
yield (entries 1 - 6). On the contray, benzyl ether deri-
vates with an electon-withdrawing group such as nitro
gave lower yield of the corresponding alkyalted products
(compare entries 1 and 17). Even worse, if arenes had a
chloride or nitro group, the FCA did not occur at all (en-
tries 7 and 8). It is worth to note that BF3.Et2O could also
efficiently promote the benzylation of heteroarenes such
as thiophene and furan to give corresponding dihet-
eroaryl-methane (entries 11 and 12), but we found that
the arene substrates containing oxygen hetero-atom gave
low yield (17% - 49%) of alkyalted product (entries 6, 10
and 12), this is possibly due to that the coordination of
the ether oxygen or phenolic oxygen with B(III) decreased
the electron density in the arene ring, and resulted in poor
reactivity. It is more interesting that oxygen heteroatom-
containing substrates such as 2f, 2j and 2l gave poor
yields of benzylated products, but better regioselectivity
was observed (compare entries 1 and 6, 10 and 12), espe-
cially for substrate 2j, 100% regioselectivity was achi-
eved (entry 10).
3. Conclusions
In conclusion, we have demonstrated a BF3·Et2O-medi-
ated benzylation of arenes and heteroarenes using benzyl
ethers as the alkylating agents. Various ethers, arenes and
heteroarenes were systematically studied, and low reac-
tivity of oxygen-hetero atom-containging arenes was also
observed. This method used inexpensive and comer-
cially available BF3·Et2O as promoter, and provided com-
plementary access to valuable diarylmethane under mild
conditions.
4. General Experimental Informatio n
Unless otherwise noted, all experiments were performed
under Ar atmosphere in a sealed tube. All reagents were
purchased from TCI, Acros or strem. Solvents were treat-
ed with 4Å molecular sieves or sodium and distilled prior
to use. Purifications of reaction products were car- ried
out by flash chromatography using silica gel (40 - 63 mm)
from Qingdao Haiyang Chemical Co. Ltd. Infrared spec-
tra (IR) were recorded on a Brucker TENSOR 27 FTIR
spectrophotometer and are reported as wavelength num-
bers (cm–1). 1H NMR spectra were recorded on a Bruker
Avance 400 MHz spectrometer. Chemical shifts are re-
ported in parts per million (ppm) and coupling con-
stants are reported as Hertz (Hz). Splitting patterns are
designated as singlet (s), broad singlet (bs), doublet (d),
triplet (t). Splitting patterns that could not be interpreted
or easily visualized are designated as multiplet (m). Low
resolution mass spectra were recorded using GC-MS.
General Procedure
Benzyl ether derivatives (0.5 mmol), arenes or heteroa-
renes (6.0 mmol), BF3.OEt2 (3.0 equiv, 1.5 mmol) and 1,
4-dioxane (1.5 mL) were combined in a pressure tube
equipped with a stir bar, The mixture was heated to given
temperature and stirred for the given time under Ar at-
mosphere. When the starting material has disappeared
(monitored by TLC), the reaction mixture was treated
with 10.0 mL of H2O, filtrated and the corresponding
filtrate was extracted with ethyl acetate (3 × 15 mL), the
combined organic layers were concentrated, and the
residue was purified by flash column chromatography (si-
lica gel) to furnish target product. All products are kno-
wn compounds and identified using 1H NMR, LRMS and
IR by comparison with previously reported data.
1-Benzyl-4-methylbenzene (3a) [31] and 1-benzyl-2-
methylbenzene (4a) [32] (3a/4a = 5:3), liquid. 3a: 1H
NMR (400 MHz, CDCl3) δ: 7.24 (d, J = 6.1 Hz, 2 H),
7.04 (m, 7 H), 3.92 (s, 2H), 2.29 (s, 3 H); 4a: 1H NMR
(400 MHz, CDCl3) δ: 7.24 (d, J = 6.1 Hz, 2 H), 7.04 (m,
7 H), 3.97 (s, 2 H), 2.22 (s, 3 H); MS (ESI): m/z =
182.26 [M]+; IR (KBr): 3294, 1720, 1597, 1443, 1332,
1210, 1167, 1027 cm–1.
4-Benzyl-1,2-dimethylbenzene (3b) [33] and 1-ben-
zyl-2,3-dimethylbenzene (4b) [34] ( 3b/4b = 5:2), liquid.
3b 1H NMR (400 MHz, CDCl3) δ: 7.28 - 7.22 (m, 2 H),
7.17 (d, J = 7.3 Hz, 2 H), 7.10 (d, J = 7.4 Hz, 1H), 7.08 -
7.00 (m, 1H), 6.99 - 6.94 (m, 1H), 6.91 (d, J = 7.6 Hz, 1
H), 3.90 (s, 2 H), 2.21 (s, 6H); 4b: 1H NMR (400 MHz,
CDCl3) δ: 7.28 - 7.22 (m, 2 H), 7.17 (d, J = 7.3 Hz, 2 H),
7.10 (d, J = 7.4 Hz, 1 H), 7.08 - 7.00 (m, 1 H), 6.99 -
6.94 (m, 1 H), 6.91 (d, J = 7.6 Hz, 1 H), 4.00 (s, 2 H),
2.27 (s, 3 H), 2.12 (s, 3 H); MS (ESI): m/z = 196.28 [M]+;
IR (KBr): 2923, 2854, 1817, 1764, 1727, 1588, 1481,
1095, 1026, 827, 741, 666, 567 cm–1.
1-Benzyl-2,4-dimethylbenzene (3c) [35] and 2-benzyl-
1,3-dimethylbenzene (4c) [33] (3c/4c = 5:1), liquid. 3c
1H NMR (400 MHz , CDCl3) δ: 7.29 - 6.90 (m, 7 H),
3.93 (s, 2 H), 2.29 (s, 3 H),2.19 (s, 3 H); 4c: 1H NMR
(400 MHz, CDCl3 ) δ: 7.29 - 6.90 (m, 7 H), 4.04 (s, 2 H),
2.23 (s, 6 H); MS (ESI): m/z = 196.34 [M]+, IR (KBr):
3119, 2921, 2853, 1742, 1696, 1516, 1462, 1355, 1229,
853, 634, 499 cm–1.
2-Benzyl-1,4-dimethylbenzene (3d) [33], liquid. 1H
NMR (400 MHz, CDCl3) δ: 7.25 (t, J = 7.4 Hz, 2 H),
7.14 (dd, J = 25.9, 8.2 Hz, 3 H), 7.04 (d, J = 7.9 Hz, 1 H),
6.97 - 6.90 (m, 2 H), 3.94 (s, 2 H), 2.28 (s, 3 H), 2.18 (s,
3 H); MS (ESI): m/z = 196.28 [M]+, IR (KBr): 2924,
2856, 1734, 1504, 1458, 1377, 811, 735, 628 cm–1.
2-Benzyl-1,3,5-trimethylbenzene (3e) [33], liquid. 1H
NMR (400 MHz , CDCl3) δ: 7.20 (d, J = 7.8 Hz, 2 H),
7.14 (d, J = 7.1 Hz, 1 H), 7.00 (d, J = 7.5 Hz, 2 H), 6.88

L. DANG ET AL.
180
(s, 2 H), 4.01 (s, 2 H), 2.28 (s, 3 H), 2.20 (s, 6 H); MS
(ESI): m/z = 210.31 [M]+, IR (KBr): 2923, 2856, 1640,
1515, 1457, 1385, 1319, 1257, 1097, 852, 691, 591 cm–1.
1-Benzyl-4-methoxybenzene (3f) [36] and 1-benzyl-2-
methoxybenzene (4d) [15] (3f/4d = 5:1), liquid. 3f: 1H
NMR (400 MHz, CDCl3 ) δ: 7.30 - 7.14 (m, 6 H), 7.08
(dd, J = 16.4, 7.5 Hz, 1 H), 6.88 – 6.80 (m, 2 H), 3.92 (s,
2 H), 3.77 (s, 3 H); 4d: 1H NMR (400 MHz, CDCl3 ) δ:
7.30 - 7.14 (m, 6 H), 7.08 (dd, J = 16.4, 7.5 Hz, 1 H),
6.88 - 6.80 (m, 2 H), 3.97 (s, 2 H), 3.80 (s, 3 H); MS
(ESI): m/z= 198.26 [M]+, IR (KBr): 3459, 2924, 2856,
1726, 1599, 1459, 1384, 1248, 1101, 1033, 740, 547 cm–1.
2-Benzylnaphthalene (3i) [37] and 1-benzylnaphtha-
lene (4f)14 (3i/4f =3:1), liquid. 3i: 1H NMR (400 MHz,
CDCl3) δ: 7.76 (dd, J = 13.3, 7.8 Hz, 3 H), 7.28 - 7.13 (m,
9 H), 4.12 (s, 2 H); 4f: 1H NMR (400 MHz, CDCl3 ) δ:
7.99 - 7.96 (m, 2 H), 7.85 - 7.84 (m, 2 H), 7.44 - 7.37 (m,
8 H), 4.43 (s, 2 H); MS (ESI): m/z = 218.29 [M]+; IR
(KBr): 3054, 2922, 2855, 1812, 1724, 1596, 1496, 1446,
1388, 1263, 1076, 856, 786, 738, 706, 590, 513 cm–1.
4-Benzylphenol (3j) [38], liquid. 3j: 1H NMR (400
MHz, CDCl3) δ: 7.31 - 7.25 (m, 2 H), 7.24 - 7.17 (m, 3
H), 7.12 (dd, J = 11.5, 4.5 Hz, 2 H), 6.91 - 6.85 (m, 1 H),
6.75 (d, J = 8.2 Hz, 1 H), 4.75 (s, 1 H), 3.98 (s, 2 H); MS
(ESI): m/z = 184.23 [M]+, IR (KBr): 3678, 3029, 2890,
2824, 1746, 1700, 1496, 1333, 844, 746 cm–1.
2-Benzylthiophene (3k) [39] and 3-benzylthiophene
(4g) 18 (3k/4g = 2:1), liquid. 3k: 1H NMR (400 MHz ,
CDCl3) δ: 7.34 - 7.10 (m, 6 H), 6.90 (d, J = 0.8 Hz, 2 H),
4.14 (s, 2 H); 4g: 1H NMR (400 MHz, CDCl3) δ: 7.34 -
7.10 (m, 6 H), 6.90 (d, J = 0.8 Hz, 2 H), 3.97 (s, 2 H);
MS (ESI): m/z = 174.29 [M]+; IR (KBr): 2923, 2855,
1739, 1639, 1458, 1384, 1264, 1203, 1264, 1203, 1096,
1030, 932, 741, 704, 558 cm–1.
2-Benzylfuran (3l) [18] and 3-benzylfuran (4h) [39]
(3l/4h = 10:1), liquid. 3l: 1H NMR (400 MHz, CDCl3) δ:
7.30 (dd, J = 12.0, 3.7 Hz, 3 H), 7.23 (d, J = 7.0 Hz, 3 H),
6.28 (dd, J = 2.9, 1.9 Hz, 1 H), 6.00 (dd, J = 3.1, 0.7 Hz,
1 H), 3.96 (s, 2 H); 4h: 1H NMR (400 MHz, CDCl3) δ:
7.30 (dd, J = 12.0, 3.7 Hz, 3 H), 7.23 (d, J = 7.0 Hz, 3 H),
6.28 (dd, J = 2.9, 1.9 Hz, 1 H), 6.00 (dd, J = 3.1, 0.7 Hz,
1 H), 3.77 (s, 2 H); MS (ESI): m/z = 158.20 [M]+; IR
(KBr): 2924, 2855, 1884, 1724, 1598, 1456, 1385, 1263,
1096, 1027 ,932, 740, 556 cm–1.
di-p-Tolylmethane (3m) [40] and o-tolyl(p-tolyl)meth-
ane (4i) [19] (3m/4i = 5:3), liquid. 3m: 1H NMR (400
MHz, CDCl3 ) δ: 7.17 - 6.95 (m, 8 H), 3.88 (s, 2 H), 2.29
(s, 6 H); 4i: 1H NMR (400 MHz, CDCl3) δ: 7.17 - 6.95
(m, 8 H), 3.93 (s, 2 H), 2.29 (s, 3 H), 2.23 (s, 3 H); MS
(ESI): m/z = 196.29 [M]+, IR (KBr): 2924, 2857, 1732,
1597, 1456, 1382, 1263, 1104, 1034, 799, 739, 607 cm–1.
1-(4-Chlorobenzyl)-4-methylbenzene (3n) [41] and 1
-(4-chlorobenzyl)-2-methylbenzene (4j) [42], (3n/4j =
10:7), liquid. 3n: 1H NMR (400 MHz, CDCl3 ) δ: 7.26 -
7.20 (m, 2 H), 7.15 (d, J = 9.1 Hz, 2 H), 7.13 - 7.00 (m, 4
H), 6.95 (d, J = 8.6 Hz, 1 H), 3.89 (s, 2 H), 2.31 (s, 3 H);
4j: 1H NMR (400 MHz,, CDCl3 ) δ: 7.26 - 7.20 (m, 2 H),
7.15 (d, J = 9.1 Hz, 2 H), 7.13 - 7.00 (m, 4 H), 3.93 (s, 2
H), 2.21 (s, 3 H); MS (ESI): m/z = 216.70[M]; IR (KBr):
2923, 2856, 1885, 1811, 1720, 1660, 1593, 1454, 1384,
1261, 1096, 798, 739, 698, 541 cm–1.
1-(4-Nitrobenzyl)-4-methylbenzene (3o) [43] and 1-
(4-nitrobenzyl)-2-methylbenzene (4k) [43] (3o/4k = 10:
7), liquid. 3o: 1H NMR (400 MHz, CDCl3 ) δ: 8.13 (dd, J
= 8.2, 3.8 Hz, 2 H), 7.33 (dd, J = 8.5, 3.6 Hz, 2 H), 7.26
(d, J = 9.3 Hz, 2 H), 7.23 - 7.16 (m, 2 H), 4.03 (s, 2 H),
2.33 (s, 3 H); 4k: 1H NMR (400 MHz, CDCl3) δ: 8.13
(dd, J = 8.2, 3.8 Hz, 2 H), 7.33 (dd, J = 8.5, 3.6 Hz, 2 H),
7.26 (d, J = 9.3 Hz, 2 H), 7.23 - 7.16 (m, 2 H), 4.08 (s, 2
H), 2.21 (s, 3 H); MS (ESI): m/z = 227.25 [M]+; IR
(KBr): 3021, 2922, 2858, 1924, 1729, 1599, 1515, 1342,
1179, 1106, 1026, 854, 736, 540 cm–1.
5. Acknowledgements
The financial supports for this work from the Program
for New Century Excellent Talents in University by Mi-
nistry of Education (Grant No. NCET-10-0371) and the
Fundamental Research Funds for the Central Universities
(Grant No. 2009ZM0262, 2009ZM0126) are gratefully
acknowledged.
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