Benzylation of arenes with benzyl halides synergistically promoted by in situ generated superacid boron trifluoride monohydrate and tetrahaloboric acid

Article abstract of DOI:10.1016/j.tet.2015.01.037

To examine the assembly methodology of diarylmethanes, a benzylation of (hetero)arenes with benzyl halides has been developed and various diarylmethanes were furnished with yields of up to 98% and regioselectivities of up to >99%. The complexation of the by-product halogen hydride with BF₃·OEt₂ generated the Bronsted acid BF₃·HX (HBF₃X, X=Cl or Br) in situ to synergistically promote the benzylation.

Full text of DOI:10.1016/j.tet.2015.01.037

Tetrahedron 71 (2015) 1540e1546
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Tetrahedron
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Benzylation of arenes with benzyl halides synergistically promoted
by in situ generated superacid boron trifluoride monohydrate and
tetrahaloboric acid
Ruofeng Huang a, Xiaohui Zhang a, Jing Pan a, Jiaqiang Li a, Hang Shen a, Xuege Ling a,
,b,
Yan Xiong a
*
a School of Chemistry and Chemical Engineering & Chongqing Key Laboratory of Chemical Process for Clean Energy and Resource Utilization,
Chongqing University, Chongqing 400044, China
b State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 21 June 2014
Received in revised form 7 January 2015
Accepted 17 January 2015
Available online 22 January 2015
To examine the assembly methodology of diarylmethanes, a benzylation of (hetero)arenes with benzyl
halides has been developed and various diarylmethanes were furnished with yields of up to 98% and
regioselectivities of up to >99%. The complexation of the by-product halogen hydride with BF3$OEt2
generated the Bronsted acid BF3$HX (HBF3X, X¼Cl or Br) in situ to synergistically promote the
benzylation.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Benzyl halides
Benzylation
BF3$OEt2
Diarylmethanes
Synergistic effects
1. Introduction
synthetic mechanisms such as alkylation,10a,b cyclization,10c,e rear-
rangement,10f and coupling reactions.10g Among these mechanisms,
Diarylmethanes are notably important fragments in supra-
molecules such as calixarene, cryptophane, and pillar[n]arene1 and
in drugs such as beclobrate, avrainvilleol, and papaverine.2 Many
cross-coupling strategies are used to synthesize these fragments,
such as Negishi reactions of benzyl halides with arylzinc reagents,3
SuzukieMiyaura reactions of benzyl reagents or diarylmethyl car-
bonates with organoboron reagents,4 and the benzylation of aro-
matic sulfinic acid sodium salts with benzyl chlorides.5 As an
alternative protocol, the direct FriedeleCrafts benzylation of (het-
ero)arenes provides an efficient method to construct diaryl-
methanes through the transformation of an unactivated CeH bond,
which involves aluminum, iron, scandium, hafnium, platinum,
lanthanum, and gold metal salts.6,7
two general reactions of BF3$OEt2 were suggested (Fig. 1): (1) In the
catalytic reaction, BF3$OEt2 exhibits the strong Lewis acidity and
high catalytic activity without any additive, and only a catalytic
amount is required;10b,d,f (2) in the second reaction, the stoichio-
metric amount of BF3$OEt2 and the addition of H2O or a moist at-
mosphere are often required to form the superacid BF3$H2O in
situ11 and BF3$OEt2 exhibits Bronsted acidity.10e,11c,12 In our former
work, the Lewis acidity of BF3$OEt2 promoted the synthesis of
bis(indolyl)methanes,10b and the Bronsted acidity of the superacid
BF3$H2O effectively promoted the benzylation of arenes with
benzyl ethers or benzyl alcohols.12f,g Here, we report the benzyla-
tion of (hetero)arene with benzyl halides, which was promoted by
a synergistic nonmetal BF3$H2O/BF3$HX system.
BF3 is a commonly used Lewis acid that has strong interactions
with numerous ligands such as carbon, nitrogen, oxygen, fluorine,
phosphorus, and sulfur, to form many of coordinate compounds.8
BF3$OEt2 is an adduct of BF3 and Et2O through a donoreacceptor
bonding9 and is capable to effectively participate in a series of
* Corresponding author. Tel.: þ86 15086903431; fax: þ86 (0)23 65112134; e-mail
address: xiong@cqu.edu.cn (Y. Xiong).
Fig. 1. Bifunction of BF3$OEt2.
http://dx.doi.org/10.1016/j.tet.2015.01.037
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

R. Huang et al. / Tetrahedron 71 (2015) 1540e1546
1541
2. Results and discussion
The model reaction resulted in a 92% isolated yield (entry 1). Benzyl
bromide reacted with toluene, which exhibited high reactivity, and
the desired product was obtained in excellent yield (entry 2). The
reaction with para-methyl-substituted benzyl bromide 1c pro-
ceeded effectively (entry 3). The substrates that included with
electron-withdrawing substituents, such as F and Cl also worked
well and produced the corresponding halo-substituted diphenyl-
methanes, which were readily further functionalized (entries 4 and
5). No benzylation product was detected with the nitro, cyano, and
ester groups as substituents on benzyl donors. When (1-
bromoethyl)benzene 1f was used, the benzylation reaction gener-
ated the product in 89% yield (entry 6). Other arenes such as 2b and
2c were surveyed and reacted with 1g, and the products 3gb and
3gc were obtained in 71% and 32% yields, respectively, both of
which can readily be converted into the drug beclobrate (entries 7
and 8).14 To our delight, our method is also suitable for ferrocene,
which yields a mono-substituted product in 21% yield (entry 9).
High regioselectivities (>87%) and excellent yields (>90%) were
detected when the (halo-methylene)dibenzenes 1h and 1i were
used (entries 10 and 11). Compared to 1i, 1-chloro-4-(chlor-
o(phenyl)methyl)-benzene 1j generated the corresponding product
with slightly lower yield and regioselectivity for the para
regioisomer, which supported the effect of the electron-
withdrawing group (entry 11).
Then, a series of reactions of (hetero)arenes with (bromo-
methylene)dibenzene were tested, where the reactivities and
regioselectivities were investigated (Table 3). Ferrocene was
a compatible substrate, which generates the mono-substituted
product in 38% yield (entry 1). The desired product 3he was ob-
tained in 92% yield with a regioselectivity of 92% (entry 2). m-
Xylene and p-xylene produced 3hf and 3hg in 83% and 84% yields,
respectively (entries 3 and 4). The reaction worked well with 2h
and 2i, which were effectively transformed into the tri-
phenylmethane derivatives with good yields (entries 5 and 6).
Ethylbenzene 2j was converted into the corresponding product in
70% yield with a regioselectivity greater than 99% (entry 7). The
reaction with benzene produced triphenylmethane in lower yield
(entry 8). Stoichiometric naphthalene dissolved in DCM served as
a highly reactive substrate and gave the corresponding product in
72% yield with a regioselectivity of 66% (entry 9). Interestingly, the
First, we investigated the effect of different conditions on the
model reaction, and the results are shown in Table 1. Without H2O,
1.5 equiv of BF3$OEt2 exhibits low reactivity, and the desired
product was obtained in 23% yield with a regioselectivity of
50:42:8 in N2 using anhydrous toluene, which indicates that
BF3$OEt2 is a low-efficiency promoter for this transformation
(entry 1). The addition of 0.2 equiv of H2O is beneficial for the
formation of BF3$H2O (maximum to 0.2 equiv) to increase the
yield to 64% (entry 2). Upon increasing the amount of H2O to
0.4 equiv (maximum to 0.4 equiv of BF3$H2O), the target product
was obtained with excellent yield (92%, p-/o-/m-¼52:42:6, entry
3). It is noteworthy that 0.4 equiv of BF3$OEt2 with 0.4 equiv of
H2O only resulted in a yield of 66% (entry 4), which indicates that
0.4 equiv of the superacid BF3$H2O is inadequate for this trans-
formation, and BF3$HX (X¼Cl),13 which originates from the ini-
tially released by-product hydrohalide (HX), efficiently promotes
this reaction. However, when the amount of H2O was increased to
0.6 equiv, the product yield dramatically decreased (34%) (entry 5).
Compared to entry 1, the reactions of BF3$OEt2 result in good yield
under open-flask conditions with anhydrous toluene or by using
undistilled toluene in a protective atmosphere (entries 6 and 7),
and the best yield of 92% was obtained with a regioselectivity of
53:41:6 when unpretreated toluene was used under the open-
flask conditions (entry 8). Throughout the investigations, traces
of residual water in air or toluene are favorable for this reaction.
Other boron species, such as H3BO3 and HBF4, were also screened
in this reaction. When H3BO3 was used as the boron reagent, no
benzylation product was detected (entry 9). The tetrahaloboric
acid HBF4 exhibits high reactivity and results in a 90% yield with
a regioselectivity of 49:44:7 under N2 protection using distilled
toluene (entry 10).
Table 1
Benzylation of toluene with benzylchloride under different conditionsa
resulting
a-diphenylmethylated naphthalene 3hl was readily
separated via recrystallization from the mixing benzylation prod-
uct of 2l, and the structure of 3hl was confirmed using X-ray
crystallographic analysis (Fig. 2).15 Heteroarene such as thiophene
was also tolerated and generated the product with 80% yield
(entry 10).
A plausible synergistic scheme is considered for a synergistic
promotion model for 1a (Scheme 1). In the presence of 0.4 equiv of
water, the precursor BF3$OEt2 (0.4 equiv), which is a low-efficiency
promoter for benzylation (Table 1, entry 1), is maximally trans-
formed into 0.4 equiv of superacid BF3$H2O,11 which only results in
a yield of 66% (Table 1, entry 4) with the successive production of
the by-product HCl via the cleavage of the CeCl bond of 1a. Ligand-
exchange occurs between BF3$OEt2 and HCl and subsequently
generates the by-product complex BF3$HCl13 (HBF3Cl, which is
structurally similar to HBF4), which acts as an efficient synergistic
promoter to generate target product 3aa.
Entry
Boron source
Toluene
Atmosphere
H2O
(equiv)
Yieldb (%)
(ratio)c
1
2
BF3$OEt2
BF3$OEt2
BF3$OEt2
BF3$OEt2
BF3$OEt2
BF3$OEt2
BF3$OEt2
BF3$OEt2
H3BO3
Dry
Dry
Dry
Dry
Dry
Dry
Undistilled
Undistilled
Undistilled
Dry
N2
N2
N2
N2
N2
Air
N2
Air
Air
N2
d
23 (50:42:8)
64 (49:43:8)
92 (52:42:6)
66 (48:44:8)
34 (51:43:6)
78 (50:44:6)
74 (52:42:6)
92 (53:41:6)
0
0.2
0.4
0.4
0.6
d
3
4d
5
6
7
8
d
d
9
d
10e
HBF4
d
90 (49:44:7)
a
Reaction conditions: (chloromethyl)benzene (1.0 mmol), toluene (2.0 mL), H2O
(specified), boron source (1.5 equiv), 2 h, reflux (120 ꢀC of oil bath).
b
Isolated yield.
c
Isomer ratios of p-/o-/m-determined by 13C NMR.
d
BF3$OEt2 (0.4 equiv) was used.
For optimal conditions, see Supplementary data.
e
3. Conclusions
After exploring the reaction conditions, our interest focused on
the effect of substituting benzyl halide in the FriedeleCrafts re-
action with undistilled arenes (Table 2). Throughout the in-
vestigations, the substitutions of benzyl donors with electron-
donating and electron-withdrawing groups slightly inhibited the
reaction and resulted in low yields, and those with neutral groups
provided better reactivities under the optimal reaction conditions.
In conclusion, a synergistic metal-free system of BF3$H2O/
BF3$HX-promoted benzylation of (hetero)arenes with benzylha-
lides has been developed, and various diarylmethanes were fur-
nished with yields of up to 98% and regioselectivities above 99%.
Moreover, a plausible synergistic scheme was introduced to in-
terpret the observed reactivities.

Table 2
Investigation of benzyl halides with arenesa
Entry
1
1 (R1, R2, X)
1a (H, H, Cl)
2
Major product
t (h)
Yieldb (%) (ratio)c
92 (53:41:6)
2
3aa
2a
2
3
4
1b (H, H, Br)
2
5
98 (51:42:7)
3ba
3ca
3da
2a
2a
2a
1c (4-Me, H, Br)
1d (4-Cl, H, Br)
67 (62:32:6) [88 (60:35:5)]d
71 (51:40:9) [88 (51:41:8)]d
10
5
6
7
1e (4-F, H, Br)
1f (H, Me, Cl)
1g (4-Cl, H, Br)
5
6
75 (51:42:7) [95 (52:40:8)]d
3ea
2a
2a
89 (84:12:4)
3fa
10
71 (>99)
3gb
2b
2c
8e
1g (4-Cl, H, Br)
1b (H, H, Br)
10
6
18 (>99)
21 (ꢁ)
3gc
9e
2d
2a
3bd
10
11
1h (H, Ph, Br)
5
93 (86:14)
3ha
1i (H, Ph, Cl)
5
5
90 (92:8)
2a
2a
3ia
12
1j (4-Cl, Ph, Cl)
85 (85:12:3)
3ja
a
Reaction conditions: benzylation agents (1.0 mmol), toluene (2.0 mL), BF3$OEt2 (1.5 equiv), reflux (120 ꢀC of oil bath) in air.
Isolated yield.
b
c
Isomer ratios of p-/o-/m-determined by 13C NMR.
d
e
H2O (0.4 equiv), N2 atmosphere.
Benzyl halide (1.0 mmol), arene (4.0 mmol), DCM (2.0 mL), reflux (120 ꢀC of oil bath), in air.

R. Huang et al. / Tetrahedron 71 (2015) 1540e1546
Table 3 (continued )
1543
Table 3
Entry
2
Major product
t (h)
Yieldb (%) (ratio)c
Exploration of the scope of arenes with (bromomethylene)dibenzenea
10e
2
80 (2-/3-¼93:7)
2m
Entry
1d
2
Major product
t (h)
Yieldb (%) (ratio)c
3hm
a
Reaction conditions: (bromomethylene)dibenzene (1.0 mmol), arene (2.0 mL),
and BF3$OEt2 (1.5 equiv), 120 ꢀC, in air.
10
38 (ꢁ)
b
Isolated yield.
Isomer ratios determined by 13C NMR.
(Bromomethylene)dibenzene (1.0 mmol), arene (4.0 mmol), DCM (2.0 mL),
c
d
2d
2e
3hd
reflux (120 ꢀC of oil bath), in air.
e
Reflux (120 ꢀC of oil bath), in air.
2
3
5
5
92 (4-/3-¼92:8)
3he
83 (4- >99%)
2f
3hf
3hg
3hh
4
5
5
5
84 (ꢁ)
2g
2h
98 (5-/6-¼66:34)d
Fig. 2. Simple operation to separate the a-diphenylmethylation product 3hl and the X-
ray structure.
6
7
5
5
83 (ꢁ)
2i
3hi
70 (p- >99%)
2j
2k
2l
3hj
3hk
3hl
Scheme 1. Proposed synergistic promotion scheme of benzylation.
4. Experimental section
8e
10
18 (ꢁ)
4.1. General information
The 1H and 13C NMR spectra were recorded in CDCl3 solution at
500/125 MHz spectrometer at 20e25 ꢀC. 11H NMR chemical shifts
were reported in parts per million (ppm) using tetramethylsilane
(TMS,
d
¼0.00 ppm) as the internal standard. The data of 1H NMR
9d
5
72 (
a
-/
b
-¼66:34)
were reported as follows: chemical shift, multiplicity (s¼singlet,
d¼doublet, t¼triplet, q¼quartet, m¼multiplet), coupling constant (J
values) in hertz (Hz), and integration. 13C NMR spectra were re-
(continued on next page)
ported in parts per million (ppm) using solvent CDCl3 (
d¼77.2 ppm)

1544
R. Huang et al. / Tetrahedron 71 (2015) 1540e1546
as an internal standard. All the reagents used were of analytical
grade, purchased locally and used without any purification unless
otherwise specified. Column chromatography was performed using
silica gel, and analytical thin-layer chromatography (TLC), which
was used to monitor the reactions was performed on silica gel plates.
Toluene distillation: toluene purchased from chemical supplier was
d
7.15e7.04 (m, 13.9H), 6.96e6.93 (m, 5H), 3.94 (s, 2H), 3.89 (s,
2.9H), 2.31 (s, 4.4H), 2.22 (s, 3H). 13C NMR: (CDCl3, 125 MHz)
d
162.5
(d, J¼8.8 Hz) (p), 160.5 (d, J¼8.6 Hz) (o), 138.9 (o), 138.1 (p), 137.3 (p),
136.7 (o), 136.2 (o), 135.9 (p), 130.6 (o), 130.4 (d, J¼7.5 Hz) (p), 130.2
(d, J¼7.6 Hz) (o), 130.0 (o), 129.8 (m), 129.4 (p), 128.9 (p), 128.6 (m),
127.1 (m), 126.8 (o), 126.2 (o), 126.0 (m), 115.4 (o), 115.2 (p), 41.2 (m),
ꢀ
firstly dried over 4 A molecular sieve for 1 week, and then transferred
to distillation apparatus under nitrogen protection. Na slice was
40.8 (p), 39.8 (o), 21.6 (m), 21.2 (p), 19.8 (o). IR:
n 739, 812, 843, 1157,
1216, 1434, 1462, 1510, 1602, 2859, 2926, 3016, 3043 cmꢁ1
.
added, andafterrefluxfor half a day, dry toluenewascollected foruse.
4.2.6. 1-Methyl-4-(1-phenylethyl)benzene (3fa). Colorless liquid,
174.2 mg, yield: 89%, p-/o-/m-¼84:12:4, 1H NMR (CDCl3, 500 MH)
4.2. Typical procedure for the benzylation of toluene with
benzyl chloride
d
7.27e7.25 (m, 2.6H), 7.22e7.21 (m, 2.4H), 7.18e7.16 (m, 1.6H), 7.09
(m, 4.2H), 4.31 (m, 0.1H), 4.12e4.10 (m, 1H), 2.30 (s, 3.1H), 2.23 (s,
To a 50 mL round flask filled with toluene (2 mL) were added
0.5H), 1.62 (m, 3.5H), 1.53 (m, 0.6H). 13C NMR (125 MHz, CDCl3,
benzyl chloride 1a (126.6 mg, 1.0 mmol) and BF3$OEt2 (188.8
m
L,
major product)
44.4, 22.0, 21.0. IR:
2875, 2923, 2965, 3024, 3058 cmꢁ1
d
146.7, 143.5, 135.5, 129.1, 128.3, 127.7, 127.6, 126.0,
1.5 mmol) in the atmosphere. Then, the reaction mixture was
refluxed in oil bath of 120 ꢀC and the stirring was turned on. After
2 h, the stirring stopped, reaction mixture was cooled to room
temperature, and the toluene was removed to get thick residue
under reducing pressure. The resulting residue was purified by flash
column chromatography on silica gel column using petroleum ether
as eluant to afford a colorless oil product (160.4 mg, 92% yield).
n
697, 756, 823,1019,1021,1451, 1494, 1513,1597,
.
4.2.7. 1-Chloro-4-(4-methoxybenzyl)benzene (3gb). White solid,
164.8 mg, yield: 71%, p- >99%; 1H NMR (CDCl3, 500 MH)
7.23 (d,
d
J¼8.0 Hz, 2H), 7.09 (d, J¼8.5 Hz, 2H), 7.07 (d, J¼8.5 Hz, 2H), 6.83 (d,
J¼8.5 Hz, 2H), 3.88 (s, 2H), 3.78 (s, 3H). 13C NMR: (CDCl3, 125 MHz)
d
158.2, 140.1, 132.7, 131.8, 130.2, 129.9, 128.6, 114.0, 55.3, 40.4. IR: n
4.2.1. 1-Benzyl-4-methylbenzene (prepared by benzyl chloride)
795, 854, 1014, 1042, 1092, 1173, 1244, 1454, 1488, 1513, 1611, 2830,
2844, 2954, 3030, 3002 cmꢁ1
(3aa). Colorless liquid, 167.4 mg, yield: 92%, p-/o-/m-¼53:41:6; 1H
.
NMR (CDCl3, 500 MHz) d 7.27e7.23 (m, 3.3H), 7.18e7.05 (m, 11.2H),
7.00e6.97 (m, 0.4H), 3.97 (s, 1.4H), 3,93 (s, 2H), 2.30 (s, 3H), 2.23 (s,
4.2.8. 2-(p-Tolylmethylene)dibenzene
(prepared
by
(bromo-
2H). 13C NMR: (CDCl3,125 MHz)
d
141.6 (p), 140.6 (o), 139.1 (o), 138.2
methylene)dibenzene) (3ha). Light yellow liquid, 240.2 mg, yield:
(p),136.8 (o),135.7 (p),130.5 (o),130.1 (o),129.9 (m),129.3 (p),129.04
(p), 129.0 (p), 128.9 (o), 128.6 (p), 128.5 (o), 127.0 (m), 126.6 (o), 126.2
93%, p-/o-¼86:14. 1H NMR (CDCl3, 500 MHz, major product)
d 7.26
(t, J¼7.0 Hz, 4H), 7.19 (t, J¼7.0 Hz, 2H), 7.11 (d, J¼7.5 Hz, 4H), 7.08 (d,
(p),126.1 (o), 42.1 (m), 41.7 (p), 39.6 (o), 21.6 (m), 21.2 (p),19.8 (o). IR:
n
J¼8.0 Hz, 2H), 7.01 (d, J¼8.0 Hz, 2H), 5.51 (s, 1H), 2.31 (s, 3H). 13
C
700, 728, 1321, 1452, 1493, 1516, 1597, 2915, 3027, 3063 cmꢁ1
.
NMR: (CDCl3, 125 MHz, major product)
129.5, 129.2, 128.4, 126.4, 56.7, 21.2. IR:
d 144.3, 141.1, 136.0, 129.6,
n
605, 697, 756, 1437, 1496,
4.2.2. 1-Benzyl-4-methylbenzene (prepared by benzyl bromide)
1504, 1594, 3024, 3058 cmꢁ1
.
(3ba). Colorless liquid, 178.6 mg, yield: 98%, p-/o-/m-¼51:42:7; 1H
NMR (CDCl3, 500 MHz)
d
7.26e7.23 (m, 3.3H), 7.17e7.05 (m, 11.1H),
4.2.9. 2-(p-Tolylmethylene)dibenzene
(prepared
by
(chloro-
7.00e6.97 (m. 0.4H), 3.97 (s, 1.4H), 3,92 (s, 2H), 2.30 (s, 3H), 2.22 (s,
methylene)dibenzene) (3ia). Light yellow liquid, 232.5 mg, yield:
2H). 13C NMR: (CDCl3,125 MHz)
d
141.6 (p), 140.6 (o), 139.1 (o), 138.2
90%, p-/o-¼92:8; 1H NMR (CDCl3, 500 MHz, major product)
d 7.26 (t,
(p),136.8 (o),135.7 (p),130.5 (o),130.1 (o),129.9 (m),129.3 (p),129.04
(p), 129.0 (p), 128.9 (o), 128.6 (p), 128.5 (o), 127.0 (m), 126.6 (o), 126.2
J¼7.0 Hz, 4H), 7.19 (t, J¼7.0 Hz, 2H), 7.11 (d, J¼7.5 Hz, 4H), 7.08 (d,
J¼8.0 Hz, 2H), 7.01 (d, J¼8.0 Hz, 2H), 5.51 (s, 1H), 2.31 (s, 3H). 13
C
(p),126.1 (o), 42.1 (m), 41.7 (p), 39.6 (o), 21.6 (m), 21.2 (p),19.8 (o). IR:
n
NMR: (CDCl3, 125 MHz, major product)
d 144.3, 141.1, 136.0, 129.6,
700, 728, 1321, 1452, 1493, 1516, 1597, 2915, 3027, 3063 cmꢁ1
.
129.5, 129.2, 128.4, 126.4, 56.7, 21.2. IR: n 605, 697, 756, 1437, 1496,
1504, 1594, 3024, 3058 cmꢁ1
.
4.2.3. Di-p-tolylmethane (3ca). Colorless liquid, 131.5 mg, yield:
67%, p-/o-/m-¼62:32:6; 1H NMR (CDCl3, 500 MHz)
d
7.16e7.12 (m,
4.2.10. 1-Chloro-4-(phenyl(p-tolyl)methyl)benzene (3ja). Colorless
liquid, 248.9 mg, yield: 85%, p-/o-/m-¼85:12:3; 1H NMR (CDCl3,
1.7H), 7.09e7.05 (m, 8.9H), 7.00 (d, J¼5.0 Hz, 1.2H), 3.94 (s, 1H), 3.90
(s, 2H), 2.30 (s, 7.6H), 2.24 (s, 1.5H). 13C NMR: (CDCl3, 125 MHz)
500 MHz, major product) d 7.28e7.20 (m, 5H), 7.15e7.14 (m, 0.5H),
d
139.4 (o), 138.5 (p), 137.5 (o), 136.8 (o), 135.6 (p), 135.5 (o), 130.4
(o), 130.0 (o), 129.29 (p), 129.25 (o), 129.0 (p), 128.8 (o), 126.5 (o),
126.1 (o), 41.3 (p), 39.2 (o), 21.2 (p), 19.8 (o). IR: 793, 800, 1012,
1121, 1323, 1443, 1494, 1507, 2920, 2996, 3022, 3046 cmꢁ1
7.08 (s, 4H), 7.03 (d, J¼7.5 Hz, 2H), 6.97 (d, J¼7.0 Hz, 2H), 5.47 (s, 1H),
2.31 (s, 3H). 13C NMR: (CDCl3, 125 MHz, major product)
143.8,
142.9, 140.6, 136.3, 132.2, 131.1, 130.9, 129.5, 129.4, 129.3, 128.6,
126.6, 56.0, 21.2. IR (KBr): 700, 748, 798, 809, 846,1014,1090,1407,
1449, 1491, 1510, 1597, 2873, 2921, 3027, 3061,3088 cmꢁ1
d
n
.
n
.
4.2.4. 1-Chloro-4-(4-methylbenzyl)benzene (3da). Colorless liquid,
153.8 mg, yield: 71%, p-/o-/m-¼51:40:9; 1H NMR (CDCl3, 500 MHz)
4.2.11. ((3,4-Dimethylphenyl)methylene)dibenzene (3he). Colorless
liquid, 250.6 mg, yield: 92%, 4-/3-¼92:8; 1H NMR (CDCl3, 500 MHz,
d
7.24e7.22 (m, 3.8H), 7.19e7.13 (m, 2.3H), 7.10e7.09 (m, 4H),
7.07e7.01 (m, 3.5H), 6.97e6.95 (m, 0.3H), 3.94 (s, 1.5H), 3.90 (s, 2H),
major product)
d
7.27 (t, J¼6.0 Hz, 4H), 7.20 (t, J¼6.5 Hz, 2H), 7.12 (d,
2.31 (s, 3.1H), 2.21 (s, 2.1H). 13C NMR: (CDCl3, 125 MHz)
d
140.6 (m),
J¼7.0 Hz, 4H), 7.04 (d, J¼6.0 Hz, 1H), 6.91 (s, 1H), 6.82 (d, J¼7.0 Hz,
140.1 (p),139.9 (m),139.0 (o),138.5 (o),138.3 (m),137.7 (p),136.7 (o),
136.0 (p), 131.95 (p), 131.86 (o), 130.6 (o), 130.4 (m), 130.4 (p), 130.2
(o), 130.0 (o), 129.8 (m), 129.4 (p), 128.9 (o), 128.69 (p), 128.66 (p),
127.2 (m), 126.9 (o), 126.3 (o), 126.0 (m), 41.4 (m), 41.0 (p), 39.0 (o),
1H), 5.48 (s, 1H), 2.23 (s, 3H), 2.19 (s, 3H). 13C NMR: (CDCl3,
125 MHz, major product)
129.6, 128.4, 127.0, 126.3, 56.7, 20.0, 19.5. IR:
1494, 1597, 2875, 2915, 2965, 3007, 3055 cmꢁ1
d 144.4, 141.5, 136.6, 134.6, 130.1, 129.7,
n
697, 734, 750, 1443,
.
21.6 (m), 21.2 (o), 19.8 (p). IR:
n 742, 795,1014,1087, 1334,1406,1451,
1493, 1521, 2921, 2971, 3022, 3044 cmꢁ1
.
4.2.12. ((2,4-Dimethylphenyl)methylene)dibenzene (3hf). Colorless
liquid, 226.1 mg, yield: 83%, 4- >99%; 1H NMR (CDCl3, 500 MHz,
4.2.5. 1-Fluoro-4-(4-methylbenzyl)benzene (3ea). Colorless liquid,
150.2 mg, yield: 75%, p-/o-/m-¼51:42:7; 1H NMR (CDCl3, 500 MHz)
major product)
d
7.26 (t, J¼6.5 Hz, 4H), 7.20 (t, J¼6.5 Hz, 2H), 7.05 (d,
J¼6.5 Hz, 4H), 6.99 (s, 1H), 6.90 (d, J¼7.0 Hz, 1H), 6.69 (d, J¼7.0 Hz,

R. Huang et al. / Tetrahedron 71 (2015) 1540e1546
1545
1H), 5.63 (s,1H), 2.29 (s, 3H), 2.17 (s, 3H). 13C NMR: (CDCl3,125 MHz,
major product) 143.7, 139.5, 136.5, 135.9, 131.4, 129.7, 129.5, 128.4,
126.5, 126.3, 53.3, 21.0, 19.9. IR: 703, 731, 756, 1454, 1496, 1600,
2921, 3021, 3058, 3080 cmꢁ1
2H), 7.09 (d, J¼8.0 Hz, 2H), 7.02 (d, J¼8.0 Hz, 2H), 6.75 (d, J¼7.5 Hz,
2H), 4.71 (s, 1H), 3.87 (s, 2H). 13C NMR: (CDCl3, 125 MHz)
154.2,
140.2, 133.0, 132.0, 130.3, 130.2, 128.7, 115.6, 40.5. IR (KBr): 548,
809, 1011, 1087, 1104, 1224, 1435, 1446, 1485, 1507, 1597, 2830, 2811,
2828, 3041, 3057, 3422 cmꢁ1. HRMS (ESI) calcd for C13H11ClO
[MþH]þ 218.0498, found 218.0418.
d
d
n
n
.
4.2.13. ((2,5-Dimethylphenyl)methylene)dibenzene (3hg). Colorless
liquid, 230.3 mg, yield: 84%; 1H NMR (CDCl3, 500 MH)
7.27e7.20 (m,
6H), 7.06e7.05 (m, 5H), 6.95 (d, J¼7.0 Hz,1H), 6.62 (s,1H), 5.64 (s,1H),
2.20 (s, 3H), 2.16 (s, 3H). 13C NMR: (CDCl3, 125 MHz)
143.7, 142.2,
135.2,133.6,130.5,130.3,129.8,128.4,127.2,126.3, 53.6, 21.4,19.7. IR:
610, 697, 745, 854,1373,1446,1491,1597, 2853, 2915, 3055, 3078 cmꢁ1
d
4.3.2. Benzylferrocene (3bd). Orange solid, 58.0 mg, yield: 21%, 1H
d
NMR (CDCl3, 500 MH)
4.12e4.12 (m, 5H), 4.09e4.08 (m, 4H), 3.69 (s, 2H). 13C NMR: (CDCl3,
125 MHz) 141.8, 128.6, 128.4, 126.1, 88.1, 68.8, 67.7, 53.6, 36.22. IR
(KBr):
d 7.28e7.25 (m, 2H), 7.18e7.17 (m, 3H),
n
.
d
n
490, 720, 801, 821, 1034, 1025, 1106, 1429, 1443, 1491, 2887,
4.2.14. ((2,4,5-Trimethylphenyl)methylene)dibenzene (3hh). White
solid, 280.1 mg, yield: 98%, 5-/6-¼66:34; 1H NMR (CDCl3, 500 MHz,
2926, 3021, 3072, 3439 cmꢁ1. HRMS (ESI) calcd for C17H16Fe
[MþH]þ 276.0601, found 276.0602.
major product)
d
7.27 (t, J¼7.5 Hz, 4H), 7.20 (t, J¼6.5 Hz, 2H), 7.06 (d,
J¼7.0 Hz, 4H), 6.94 (s, 1H), 6.56 (s, 1H), 5.61 (s, 1H), 2.20 (s, 3H), 2.14
4.3.3. Diphenylmethylferrocene (3hd). Orange solid, 133.8 mg,
(s, 3H), 2.11 (s, 3H). 13C NMR: (CDCl3, 125 MHz, major product)
yield: 38%; 1H NMR (CDCl3, 500 MH)
d
7.27e7.24 (m, 4H), 7.18e7.16
(m, 6H), 5.14 (s, 1H), 4.15e4.14 (m, 4H), 3.99 (s, 5H). 13C NMR:
(CDCl3, 125 MHz) 154.2, 128.9, 128.2, 126.3, 91.8, 69.0, 68.9, 67.8,
52.0. IR (KBr): 515, 630, 703, 725, 809, 826, 1000, 1025, 1106, 1449,
d
143.9, 139.8, 134.5, 133.8, 133.7, 132.0, 130.9, 129.8, 128.4, 126.3,
53.4, 19.7, 19.5, 19.4. IR (KBr): 702, 728, 748, 1445, 1496, 1602,
2862,3005, 3022, 3064 cmꢁ1
n
d
.
n
1491, 1600, 2990, 3016, 3103, 3442 cmꢁ1. HRMS (ESI) calcd for
4.2.15. (Mesitylmethylene)dibenzene (3hi). White solid, 237.2 mg,
yield: 83%; 1H NMR (CDCl3, 500 MH)
7.26 (t, J¼6.5 Hz, 4H), 7.19 (t,
J¼6.0 Hz, 2H), 7.09 (d, J¼7.0 Hz, 4H), 6.85 (s, 2H), 5.99 (s,1H), 2.28 (s,
3H), 1.99 (s, 6H). 13C NMR: (CDCl3, 125 MHz)
142.7, 137.7, 137.2,
136.2, 130.3, 129.5, 128.3, 126.1, 51.2, 22.2, 21.0. IR (KBr): 619, 714,
739, 812, 1446, 1491, 1600, 2859, 2915, 3019, 3043 cmꢁ1
C
23H20Fe [MþH]þ 352.0914, found 352.0903.
d
4.3.4. 1-Benzhydrylnaphthalene (3hl0). White solid, 212.0 mg,
d
yield: 72%,
a
-/
b
-¼66:34; 1H NMR (CDCl3, 500 MH)
d8.00 (d,
n
J¼8.0 Hz, 1H), 7.87 (d, J¼8.0 Hz, 1H), 7.82e7.80 (m, 0.4H),
7.78e7.75 (m, 1.3H), 7.73e7.71 (m, 0.5H), 7.50e7.35 (m, 4.5H),
7.33e7.26 (m, 6.4H), 7.25e7.22 (m, 2.8H), 7.18 (d, J¼7.0 Hz 1.7H),
7.14 (d, J¼7.5 Hz, 4H), 6.97 (d, J¼7.5 Hz, 1H), 6.30 (s, 1H), 6.23 (s,
.
4.2.16. ((4-Ethylphenyl)methylene)dibenzene (3hj). White solid,
190.7 mg, yield: 70%, p- >99%; 1H NMR (CDCl3, 500 MHz, major
1H), 5.73 (s, 0.4H). 13C NMR: (CDCl3, 125 MHz)
d 143.9 (a-), 141.7
product)
d
7.27 (t, J¼7.0 Hz, 4H), 7.20 (t, J¼7.0 Hz, 2H), 7.12e7.11 (m,
(
(
(
(
(
b
a
b
b
a
-), 140.1 (
-), 129.8 (
-), 127.8 (
-), 125.8 (
-). IR (KBr):
a
b
a
b
-), 134.1 (
-), 128.9 (
-), 127.7 (
-), 125.6 (
613, 720, 778, 791, 811, 1390, 1446, 1491, 1594,
a
b
b
a
-), 133.6 (
-), 128.6 (
-), 127.5 (
-), 125.4 (
b
a
a
-), 132.3 (
-), 128.3 (
-), 126.6 (
-), 124.5 (
b
b
-), 132.1 (
-), 128.1 (
a
a
a
-), 129.9
-), 128.0
-), 126.2
6H), 7.02 (d, J¼7.0 Hz, 2H), 5.52 (s, 1H), 2.62 (quart, J¼7.5 Hz, 2H),
1.22 (t, J¼7.5 Hz, 3H). 13C NMR: (CDCl3, 125 MHz, major product)
a-), 126.3 (
d
144.3, 142.3, 141.3, 129.6, 129.5, 128.4, 127.9, 126.4, 56.7, 28.6, 15.7.
a
a-), 57.1 (b-), 53.3
IR (KBr):
n
605, 694, 751, 1412, 1454, 1494, 1510, 1597, 2867, 2926,
n
2963, 3022, 3061 cmꢁ1
.
3027, 3058, 3083 cmꢁ1
.
4.2.17. Triphenylmethane (3hk). White solid, 44.1 mg, yield: 18%;
1H NMR (CDCl3, 500 MH)
d
7.27 (t, J¼7.5 Hz, 6H), 7.20 (t, J¼7.5 Hz,
4.4. Typical procedure for control experiment under nitrogen
3H), 7.11 (d, J¼7.5 Hz, 6H), 5.55 (s, 1H). 13C NMR: (CDCl3, 125 MHz)
d
144.1, 129.6, 128.5, 126.5, 57.0. IR (KBr):
n
605, 700, 736, 759, 1437,
To a 50 mL three-necked bottle filled with distilled toluene
(2 mL), benzyl chloride 1a (126.6 mg, 1.0 mmol), BF3$OEt2
1448, 1496, 1600, 2851, 2929, 3016, 3052, 3077 cmꢁ1
.
(188.8
mL, 1.5 mmol), and water (7.2 mL, 0.4 mmol) were added
4.2.18. 2-Benzhydrylthiophene (3hm). White solid, 200.1 mg, yield:
under nitrogen atmosphere. Reaction mixture was refluxed in oil
bath of 120 ꢀC for 2 h. After completion of the reaction, reaction
mixture was cooled to room temperature and toluene was re-
moved by vacuum rotary evaporator. The resulting residue was
purified by flash column chromatography on silica gel column
using petroleum ether as eluant to afford a colorless oil product
(163.1 mg, 92% yield).
80%, 2-/3-¼93:7; 1H NMR (CDCl3, 500 MHz, major product)
d 7.30
(t, J¼6.5 Hz, 4H), 7.24e7.21 (m, 7H), 6.93 (s, 1H), 6.69 (s, 1H), 5.68 (s,
1H). 13C NMR: (CDCl3, 125 MHz, major product)
128.6, 126.9, 126.7, 126.5, 52.3. IR (KBr): 622, 700, 759, 1031, 1076,
1227, 1431, 1446, 1494, 1603, 3022, 3058, 3100 cmꢁ1
d 148.1, 144.0, 129.0,
n
.
4.3. Typical procedure for the benzylation of (hetero)arenes
using DCM as solvent
4.5. Procedure for separation of
product
a-diphenylmethylation
To a 50 mL round flask, (bromomethylene)dibenzene (247.1 mg,
1.0 mmol) and naphthalene (512.8 mg, 4.0 mmol) were dissolved in
2 mL of DCM. Then, BF3$OEt2 (188.8
mL, 1.5 mmol) was added. The
To a 50 mL round flask, the mixing product 3hl0 (50 mg) was
dissolved in 0.5 mL of dichloromethane and petroleum ether
(2.5 mL) was dropped slowly. Then, the mixture was transferred
into ꢁ20 ꢀC. After standing for 20 h, white crystals appeared, the
resulting reaction mixture was transferred into an oil bath of 120 ꢀC
and refluxed for 5 h in the atmosphere. After completion of the
reaction, reaction mixture was cooled to room temperature and the
solvent was removed by vacuum rotary evaporator. The resulting
residue was purified by flash column chromatography on silica gel
column using petroleum ether as eluant to afford 3hl as a white
solid product (212.1 mg, 72% yield).
mother solvent was poured out to obtain
a-diphenylmethylated
naphthalene 3hl (38.4 mg, 77% yield).
4.5.1. 1-Benzhydrylnaphthalene (after recrystallization) (3hl). White
solid, 25.4 mg, yield 77%; 1H NMR (CDCl3, 500 MH)
8.00 (d,
d
4.3.1. 4-(4-Chlorobenzyl)phenol (3gc). Light yellow solid, 70.8 mg,
J¼7.5 Hz,1H), 7.86 (d, J¼8.0 Hz,1H), 7.76 (d, J¼8.0 Hz,1H), 7.46e7.35
yield: 32%, p- >99%; 1H NMR (CDCl3, 500 MH)
d
7.24 (d, J¼7.0 Hz,
(m, 3H), 7.29 (t, J¼7.5 Hz, 4H), 7.24 (t, J¼6.5 Hz, 2H), 7.13 (d, J¼7.5 Hz,

1546
R. Huang et al. / Tetrahedron 71 (2015) 1540e1546
Tsuchimoto, T.; Tobita, K.; Hiyama, T.; Fukuzawa, S. J. Org. Chem. 1997, 62,
n 614, 717, 784, 813,
4H), 6.95 (d, J¼7.5 Hz, 1H), 6.23 (s, 1H). IR (KBr):
6997e7005; (c) Shiina, I.; Suzuki, M. Tetrahedron Lett. 2002, 43, 6391e6394; (d)
Mertins, K.; Iovel, I.; Kischel, J.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed. 2005,
44, 238e242; (e) Wang, F.; Ueda, W. Chem.dEur. J. 2009, 15, 742e753; (f) Noji,
M.; Ohno, T.; Fuji, K.; Futaba, N.; Tajima, H.; Ishii, K. J. Org. Chem. 2003, 68,
9340e9347; (g) Iovel, I.; Mertins, K.; Kischel, J.; Zapf, A.; Beller, M. Adv. Synth.
Catal. 2006, 348, 691e695.
1390, 1446, 1491, 1594, 3027, 3083 cmꢁ1
.
Acknowledgements
We gratefully acknowledge funding from the National Natural
Science Foundation of China (No. 21372265 and No. 61271059), the
Natural
(cstc2013jcyjA10037), the Scientific Research Foundation for the
Returned Overseas Chinese Scholars, Ministry of Education, and the
Fundamental Research Funds for the Central Universities (No.
CQDXWL-2013-Z012 and No. CDJZR14225502).
7. For benzylation reactions using benzyl halides as benzylation agents, see: (a)
Sarca, V. D.; Laali, K. K. Green Chem. 2006, 8, 615e620; (b) Kawada, A.; Mita-
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Science
Foundation
Project
of
CQ
CSTC
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Supplementary data
€
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.01.037.
X. F.; Xiong, Y.; Ling, X. G.; Xie, X. M.; Yuan, J.; Zhang, S. T.; Song, Z. R. Chin.
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