Acidic-functionalized ionic liquid as an efficient, green, and metal-free catalyst for benzylation of sulfur, nitrogen, and carbon nucleophiles to benzylic alcohols

Article abstract of DOI:10.1016/j.tet.2012.11.045

A series of HSO^4- functionalized ILs was synthesized and used as efficient, green, and metal-free catalysts for benzylation. Notably, the catalytic system has wide substrate scopes and the ionic liquid catalysts were applied to investigate three different types of nucleophiles to give the desired benzylation products with moderate to excellent yields.

Full text of DOI:10.1016/j.tet.2012.11.045

Tetrahedron 69 (2013) 1166e1174
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Acidic-functionalized ionic liquid as an efficient, green, and metal-free
catalyst for benzylation of sulfur, nitrogen, and carbon nucleophiles to
benzylic alcohols
*
*
Xue-Qiang Chu, Ran Jiang, Yi Fang, Zheng-Yang Gu, Hua Meng, Shun-Yi Wang , Shun-Jun Ji
Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
a r t i c l e i n f o
a b s t r a c t
ꢀ
Article history:
A series of HSO4 functionalized ILs was synthesized and used as efficient, green, and metal-free cata-
Received 28 September 2012
Received in revised form 5 November 2012
Accepted 13 November 2012
Available online 20 November 2012
lysts for benzylation. Notably, the catalytic system has wide substrate scopes and the ionic liquid cata-
lysts were applied to investigate three different types of nucleophiles to give the desired benzylation
products with moderate to excellent yields.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Acidic-functionalized ionic liquid
Alcohols
Benzylation
Metal-free
1. Introduction
Over the past decades, ionic liquid (IL) research is undergoing an
unprecedented explosion of interest, due to their particular phys-
icochemical properties, such as negligible vapor pressure, excellent
chemical, and thermal stability, good solvating ability, ease of
recyclability and their potential to enhance reaction rates.1 Some
have been successfully used as an environmentally friendly alter-
native to conventional organic solvents or catalysts in a number of
reactions,2 such as DielseAlder reaction,3 FriedeleCrafts reaction,4
esterification,5 cracking reactions.6 Among them, acidic-function-
alized ILs has been intensively studied.7 Especially, Brønsted acidic
task-specific ionic liquids (TSILs) (Fig. 1), combining some useful
characteristics of solid acids and mineral acids, which have been
exploited as efficient catalysts and generally can afford higher
yields and selectivities in chemical processes.8
The alkylation reaction of activated nucleophilic reagents, such as
thiols, amines, indoles, is used as a powerful tool for the formation of
carbonecarbon and carboneheteroatom bonds, especially the ben-
zylation (Scheme 1). The benzyl motif is ubiquitous in the realms of
pharmacologically active agents and natural products. Particularly,
N-benzyl amine scaffold and C3-benzyl indoles exhibit a wide range
of biological activities. For example, N1-benzyl-N2,N2-dimethyl-N1-
phenylethane-1,2-diamine, which is known as Antergan (Fig. 2, A),9
Fig. 1. Reported Brønsted acidic task-specific ionic liquids (TSILs) used in chemical
processes.
is among the first antihistamine drugs to be sold and its structure
provide the framework for antihistamine agents; B has effective
antioxidant power and radical scavenging activities (Fig. 2, B).10
Generally, this transformation is performed with benzyl halides
or activated benzyl alcohols,11 in presence of stoichiometric amount
of base, which results in the generation of large quantities of waste
salts, have intrinsic drawbacks in terms of atom economy (Scheme
1, path A).12 One popular concept to overcome the poor reactivity of
the most benzylic alcohols is to temporarily convert them into
corresponding carbonyl intermediates by the metal-catalyzed re-
moval of hydrogen, which is well known as ‘Hydrogen autotransfer
processes’ (Scheme 1, path B).13 Another proposed mechanism is
carbocation mechanism (Scheme 1, path C), using Lewis acid or
Brønsted acids, such as BF3$OEt2,14 InCl3,15 Bi(OTf)3,16 or H-
* Corresponding authors. E-mail addresses: shunjun@suda.edu.cn, chemjsj@su-
da.edu.cn (S.-J. Ji).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.11.045

X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
1167
2), as metal-free, green, and efficient catalysts for the benzylation of
benzothiazole-2-thiols, N-containing substrates, and indoles, and
synthesize a series of S, N, C-benzyl scaffold derivatives under mild
conditions.
2. Results and discussion
As we know, sulfur-containing compounds are difficult to use in
the presence of Lewis acidic metals because of their strong co-
ordinating and adsorptive properties to poison these catalysts, al-
though some advances have been developed.23 Therefore, the
development of a more efficient catalytic system for benzylation of
thiols becomes highly desirable. ꢀTo verify the practicability of the
projected route, a series of HSO4 based ILs with different cations
were synthesized according to our previous methods (Scheme 2)22
with some changes and their performance in the direct nucleo-
philic substitution of alcohols was studied.1,3-Benzothiazole-2-thiol
(1a), the fragment is featured in a wide variety of pharmacologically
and biologically active compounds,12 could be used in the model
reaction as an agent reacted with (4-methoxy-phenyl)-methanol
(2a) to synthesize benzylic thioethers, the results are shown in Table
1. At the outset, the reaction was carried out in the presence of an
ionic liquid a (10 mol %) at room temperature in various solvents for
24 h (Table 1, entries 1e8). When CH3CN or CHCl3 was selected as the
solvent, the desired product 2-(4-methoxy-benzylsulfanyl)-benzo-
thiazole (3aa) was obtained in 86% yield (Table 1, entries 4 and 8).
Other solvents, such as toluene, EtOH, DMF, DMSO, and THF, were
inferior to CH3CN (Table 1, entries 2e7). Additionally, further ex-
pansion of this protocol to other thiols compounds was limited, al-
though the highest yield (87%) of product 3aa was obtained when
water was employed (Table 1, entry 1). Subsequently, other func-
tionalized ionic liquids were investigated (Table 1, entries 9e15).
Interestingly, it was found that the yield decreased with the carbon
number of the side chain of imidazolium cations increasing from five
to eight and dramatically increased when further increasing the
carbon number. Only 26% yield was obtained when [BnMIm]HSO4
wasused(Table 1, entry 15). The results indicated that the side chain
has a certain impact on the activities of ionic liquids, b and f were
found to be the most effective (Table 1, entries 9 and 13). Compared
with these ionic liquids, NaHSO4 was selected as the candidate here
to determine whether the catalytic reactivities of ionic liquids were
due to the same anion (Table 1, entries 3, 4 and 7). Otherwise, only
low yield of the desired product was produced (see the Supple-
mentary data, Table S1), making us confirmed that ionic liquids
present high activity primarily ascribed to its imidazole cation. We
also screened other commonly used Brønsted or Lewis acid cata-
lysts, no better results were observed in these cases (Table 1, en-
tries 16 and 18).
Scheme 1. Nucleophilic substitution reactions of alcohols by preactivation (A) and
direct catalytic substitutions (B) and (C).
Fig. 2. The medicinal and other applications of N-benzyl amine scaffolds (A) and C3-
benzyl indoles (B).
montmorillonite,17 p-toluenesulfonic acid,18 triflic acid,19 benz-
hydryl alcohols can be turned to carbocations, which are then
attacked by nucleophiles.
Almost all of these catalytic systems suffered from below one or
more disadvantages: (1) expensive transition metals with additives
are essential; (2) the catalysts are sensitive to air; (3) nucleophiles
are excessive. To the best of our knowledge, the direct benzylation
reactions catalyzed by acidic-functionalized ionic liquids are still
relatively rare.20 Moreover, when we are preparing this paper, Xia’s
group reported sulfonic acid-functionalized ionic liquids used as
catalysts for the direct amination of alcohols.8d However, in our
method more inexpensive acidic-functionalized ionic liquids cata-
lysts could be obtained with simple work-up. On the other hand,
rarely reported catalysts were applied to investigate three different
types of nucleophiles in details. As a continuation of our interests in
ILs mediated reactions21 and acidic-functionalized ionic liquids
catalyzed reactions,22 herein, we report the development of a sim-
ple procedure utilizing acidic-functionalized ionic liquids (Scheme
With the optimal reaction conditions in hand, we continued to
explore the scope of the reaction by using various related electron-
rich alcohols and the results were summarized in Table 2. Similar to
the case of 2a, the reaction of benzothiazole-2-thiol (1a) with
benzylic alcohols bearing donating groups, such as methoxyl and
methyl, moderate to high yields S-alkylated products could be
formed (Table 2, entries 1e4). It is noteworthy that benzylic alcohol
with steric hindered substituents at 2-position has dramatic det-
rimental effect on this reaction. Moreover, benzylic alcohols bear-
ing two or more substituted methoxyl groups showed good
activities, owing to the electronic effect and sometimes steric effect,
and the corresponding products were obtained with 84% and 71%
yields, respectively (Table 2, entries 2 and 3). Further, the condi-
tions were also applied to the reaction with other aromatic alco-
hols, such as thiophen-2-yl-methanol (2e) and benzo[1,3]dioxol-5-
yl-methanol (2f), affording the designed products with 49% and
72% yields, respectively (Table 2, entries 5 and 6). Secondary alco-
hol, 1-(ferrocenyl) ethanol (2g) was also chosen to detect the
ꢀ
Scheme 2. Preparation of HSO4 functionalized ionic liquids.

1168
X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
Table 1
S-Alkylation of benzothiazole-2-thiol (1a) with (4-methoxy-phenyl)-methanol (2a) under various conditionsa
Entry
Catalyst
Time (h)
Solvent
Yieldb (%)
1
2
3
4
5
6
7
8
a
a
a
a
a
a
a
a
b
c
d
e
f
g
h
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
24
H2O
Toluene
EtOH
CHCl3
DMF
DMSO
THF
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
87
72
44
86
Trace
10
51
86
92
55
73
74
91
59
26
84
7
9
10
11
12
13
14
15
16
17
18
PTSAc
NaHSO4
In(OTf)3
51
a
General conditions: benzothiazole-2-thiol (1a) (1 mmol), (4-methoxy-phenyl)-methanol 2a (1.2 mmol), ionic liquid (10 mol %), at room temperature.
Isolated yield based on benzothiazole-2-thiol (1a) as limiting reagent.
PTSA¼p-toluenesulfonic acid.
b
c
Table 2
S-Alkylation of benzylic alcohols and other electron-rich alcohols with thiolsa
Entry
1
2
Products
Time (h)
Yieldb (%)
1
24
91
1a
1a
1a
1a
2a
3aa
2
3
4
24
24
24
84
71
2b
3ab
2c
3ac
71c
2d
3ad

X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
1169
Table 2 (continued )
Entry
1
2
Products
Time (h)
48
Yieldb (%)
5
6
49
2e
1a
3ae
48
72
1a
1a
2f
3af
7
8
40
48
83
2g
3ag
64d
1b
2a
3ba
a
General conditions: thiols 1 (1 mmol), benzylic alcohols 2 (1.2 mmol), ionic liquid f (10 mol %), MeCN (2 ml), at room temperature.
Isolated yield.
The reaction was carried out in CHCl3.
The reaction was carried out in ionic liquid b.
b
c
d
generality of alcohol substrate, displayed a high reactivity to give
2-thiol with benzylic alcohols, we were eager to explore whether
the present protocol was general enough to construct the N-al-
kylation compounds with wider structural diversity. Thus, we
turned our attention to extend our nucleophile to aniline. The de-
tails of results were listed in Tables 3 and 4. It was a bit regret that
when 4-nitroaniline (1c) was used as a reactant firstly, only a low
amount of the desired N-alkylation products was detected, even
with prolonged reaction time under the established condition
(Table 3, entry 1). In this case, an elevated reaction temperature was
tried, making the system fairly complicated, side product such as
over-alkylated product, N,N-bis(4-methoxybenzyl)-4-nitroaniline
3caa was got (Table 3, entry 2). To circumvent such a problem,
the product in 83% yield (Table 2, entry 7). When benzothiazole-2-
thiol with an electron-donating group at 5-position was introduced
to this system, still proceeded smoothly to generate S-alkylated
product (Table 2, entry 8). But when the methoxyl group at 6-
position of 2, no desired product was isolated. Meanwhile, at-
tempt of using the 1a with electron-withdrawing substituents was
not completely successful. The low yields in these cases were
presumably due to the electronic effects, which could reduce the
nucleophilicity of the mercaptan.
Encouraged by the above successful access to a variety of un-
symmetrical benzylic thioethers via S-alkylation of benzothiazole-
Table 3
N-Alkylation of 4-nitroaniline (1c) with (4-methoxy-phenyl)-methanol (2a) under various conditionsa
Entry
1c (mmol)
2a (mmol)
Time (h)
Temp (ꢁC)
Yieldb (%)
1
2
3
4
5
6
1
1
1
1.2
1
1.2
1.2
1
1
2
48
22
22
22
22
22
25
50
50
50
50
80
51
56 (20c)
55 (22)
62
48 (40)
75
1.2
1
a
General conditions : 4-nitroaniline 1c (1 mmol), (4-methoxy-phenyl)-methanol 2a (1 mmol), ionic liquid f (10 mol %), MeCN (2 ml).
Isolated yield.
The yield of over-alkylated product, N,N-bis(4-methoxybenzyl)-4-nitroaniline 3caa.
b
c

1170
X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
Table 4
N-Alkylation of benzylic alcohols and other electron-rich alcohols with anilinesa
Entry
1
Amine
Alcohol
Products
Time (h)
22
Yieldb (%)
75
1ca
1c
2a
2
3
4
23
23
24
65
44
75
1d
1da
3ea
3fa
3ga
2a
2a
2a
2a
1e
1f
5
6
18
22
65
80
1g
3ha
3ia
1h
2a
2a
7
24
40
24
24
25
10
47
61
1i
8
3ja
1j
2a
2a
2a
9
1k
1l
3ka
10
3la

X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
1171
Table 4 (continued )
Entry
Amine
Alcohol
Products
Time (h)
24
Yieldb (%)
11
12
84
79
3cc
1c
2c
24
22
2h
1c
3ch
13
91
1c
2i
3ci
a
Reaction conditions: N-containing substrates (1.2 mmol), benzylic alcohols (1.0 mmol), ionic liquid f (10 mol %), MeCN (2 ml), at 80 ꢁC.
Isolated yield.
b
we conceived that the proportion of reactants might be a potential
impact factor. In view of this, several typical ratio was tested (Table
3, entries 3e5). To our delight, 1c:2a¼1.2:1.0 was found to be the
best one for the reaction (Table 3, entry 4). The remarkable im-
provement of the yield (75%) was observed by increasing the
temperature to 80 ꢁC (Table 3, entry 6).
This result prompted us to investigate the use of other related
substituted anilines. As is shown, the presence of a strong electron-
withdrawing group (NO2) at the ortho, meta and para position of
aniline were well tolerated, 75%, 65% and 44% yields were obtained,
respectively, despite sometimes steric effect (Table 4, entries 1e3).
Compounds 1f and 1g also proceeded smoothly to give the pro-
duces (Table 4, entries 4e5). The presence of a weak electron-
withdrawing group, such as halogens at the para position of ani-
line obviously reduced the reactivity presumably owing to the
electronic effect (Table 4, entry 7). What’s more, aniline with an
electron-donating group (OMe), was almost inert to the N-alkyl-
ation reaction, albeit with a prolonged reaction time (Table 4, entry
8). Another N-containing substrate, benzo[d]thiazol-2-amine 1k
still proceeded smoothly, and 47% yield was got (Table 4, entry 9).
Nevertheless, 1H-benzo-[d][1,2,3]triazole 1l demonstrated high
efficiency to give the product 3la in moderate yield (Table 4, entry
10). Beside, 4-nitroaniline (1c) was also worked well to couple with
other active benzylic alcohols, providing the target products in
medium to good yields. And secondary alcohols, 1-(ferrocenyl)
ethanol (2g) and diphenyl-methanol (2h) were also selected to
detect the generality of alcohol substrates, demonstrated a high
reactivity to give the products in 79% and 91% yields, respectively
(Table 4, entries 12 and 13).
Subsequently, we also applied this reaction system to the direct
alkylation of indole and its derivatives. It was found that the re-
action between indoles and (4-methoxy-phenyl)-methanol (2a)
also proceeded smoothly to give C3-alkylated products with
moderate to good yields (Scheme 3).
The recovery and reuse of catalyst were highly preferable in
terms of green chemistry. To test the catalyst reusability, the re-
action was carried out in the presence of a catalytic amount of
[PMIm]HSO4 (f) under the optimal reaction conditions with ben-
zothiazole-2-thiol (1a) and (4-methoxy-phenyl)-methanol (2a) as
Scheme 3. The benzylation of indoles at the C3-position with benzylic alcohols.
the substrates. Unfortunately, after three cycles, the isolated yield
of the product was obviously decreased and ionic liquid f couldn’t
be reused with significant loss of the activities (see the Supple-
mentary data, Fig. S1).
3. Conclusion
In summary, a series of inexpensive acidic-functionalized ionic
liquids catalysts could be obtained with simple work-up, applied to
investigate three different types of nucleophiles including thiols,
anilines and indoles to various benzylic alcohols, and S-alkylated,
N-alkylated, C-alkylated compounds have been successfully re-
alized in details. The advantages of this protocol are moderate to
good yield, mild conditions, using inexpensive acidic-
functionalized ionic liquids b and f as a green and metal-free cat-
alysts, environmentally friendly. Efforts to elucidate the exact
mechanism of reaction and expand the scope of reaction type are
currently under way in our laboratory.

1172
X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
4. Experimental section
J¼8.1 Hz, 1H), 7.03 (d, J¼8.1 Hz, 1H), 7.13 (s, 1H), 7.37 (t, J¼7.4 Hz, 1H),
7.48 (t, J¼7.5 Hz,1H), 7.89 (d, J¼8.0 Hz,1H), 8.01 (d, J¼7.9 Hz,1H) ppm.
13C NMR (100 MHz, DMSO-d6):
4.1. General
d¼166.2, 152.6, 148.6, 148.3, 134.6,
126.34, 121.7, 121.4, 121.1, 112.8, 111.7, 55.4, 55.3, 36.8 ppm. HRMS
Melting points were recorded on an Electrothermal digital
melting point apparatus and were uncorrected. IR spectra were
recorded on a Varian FT-1000 spectrophotometer using KBr optics.
1H NMR and 13C NMR spectra were recorded on a Varian INOVA 300
or 400 MHz (1H NMR) and 75 or 100 MHz (13C NMR) spectrometer
using CDCl3 or DMSO-d6 as solvent and TMS as internal standard.
High resolution mass spectra were obtained using GCT-TOF in-
strument with EI or ESI source.
(ESI): calcd for C16H16N1O2S2: [MþH]þ 318.0622, found: 318.0625.
4.4. 2-((2,3,4-Trimethoxybenzyl)thio)benzo[d]thiazole (3ac)
White solid (246.7 mg, yield 71%). Mp 91.0e92.4 ꢁC. IR (KBr):
n
¼3450, 2937, 1590, 1466, 1279, 1003, 740 cmꢀ1. 1H NMR (400 MHz,
DMSO-d6):
d
¼3.77 (s, 3H), 3.78 (s, 3H), 3.89 (s, 3H), 4.56 (s, 2H), 6.76
(d, J¼8.5 Hz, 1H), 7.19 (d, J¼8.5 Hz, 1H), 7.37 (t, J¼7.4 Hz, 1H), 7.48 (t,
J¼7.4 Hz, 1H), 7.90 (d, J¼8.0 Hz, 1H), 8.01 (d, J¼7.8 Hz, 1H) ppm. 13
C
4.1.1. Typical procedure for the benzylation of thiols with benzylic
alcohols. Thiols (1.0 mmol), benzylic alcohols (1.2 mmol), ionic
liquid (0.1 mmol), and CH3CN (2 ml) were added into a flask. Then
the mixture was vigorously stirred at room temperature, until
thiols were completely consumed as indicated by TLC analysis.
After the completion of reaction, the solvent of the resulting mix-
ture was removed with the aid of a rotary evaporator, the residue
was directly purified by flash column chromatography with ethyl
acetate and petroleum ether (1:6) as eluents to afford pure product.
NMR (100 MHz, DMSO-d6):
d¼166.3, 153.5, 152.7, 151.6, 141.7, 134.6,
126.3, 124.8, 124.4, 121.7, 121.4, 121.1, 107.6, 61.0, 60.2, 55.7,
32.0 ppm. HRMS (ESI): calcd for C17H18NO3S2 : [MþH]þ 348.0728,
found: 348.0726.
4.5. 2-((4-Methylbenzyl)thio)benzo[d]thiazole (3ad)
White solid (192.6 mg, yield 71%). Mp 50.5e51.9 ꢁC. IR (KBr):
n
¼3459, 3042, 2845, 1592, 1419, 1233, 1000, 813, 736 cmꢀ1. 1H NMR
(400MHz, DMSO-d6):
d
¼2.27 (s, 3H), 4.61 (s, 2H), 7.15 (d, J¼7.4Hz, 2H),
4.1.2. Typical procedure for the benzylation of anilines with benzylic
alcohols. Anilines (1.2 mmol), benzylic alcohols (1.0 mmol), ionic
liquid (0.1 mmol), and CH3CN (2 ml) were added into a flask. Then
the mixture was vigorously stirred at 80 ꢁC, until benzylic alcohols
were completely consumed as indicated by TLC analysis. After the
completion of reaction, the solvent of the resulting mixture was
removed with the aid of a rotary evaporator, the residue was di-
rectly purified by flash column chromatography with ethyl acetate
and petroleum ether (1:20) as eluents to afford pure product.
7.33e7.43 (m, 3H), 7.48 (t, J¼7.4 Hz,1H), 7.89 (d, J¼8.0 Hz,1H), 8.00 (d,
J¼7.9 Hz, 1H) ppm. 13C NMR (100 MHz, DMSO-d6):
¼166.1, 152.6,
d
136.8,134.6,133.2,129.1,128.9,126.3,124.4,121.7,121.1, 36.5, 20.6ppm.
HRMS (ESI): calcd for C15H14NS2: [MþH]þ 272.0568, found: 272.0563.
4.6. 2-((Thiophen-2-ylmethyl)thio)benzo[d]thiazole (3ae)
ꢁ
White solid (129.1 mg, yield 49%). Mp 50e53 C. IR (KBr):
n
¼3483, 3075, 2846, 1605, 1418, 1233, 1005, 839, 751 cmꢀ1. 1H NMR
(400 MHz, DMSO-d6):
d
¼4.90 (s, 2H), 6.93e6.98 (m, 1H), 7.18 (s,
4.1.3. Typical procedure for the benzylation of indoles with benzylic
alcohols. Indoles (1.0 mmol), benzylic alcohols (1.2 mmol), ionic
liquid (0.1 mmol) and CH3CN (2 ml) were added into a flask. Then
the mixture was vigorously stirred at 50 ꢁC, until indoles were
completely consumed as indicated by TLC analysis. After the com-
pletion of reaction, the solvent of the resulting mixture was re-
moved with the aid of a rotary evaporator, the residue was directly
purified by flash column chromatography with ethyl acetate and
petroleum ether (1:20) as eluents to afford pure product.
1H), 7.38 (t, J¼7.5 Hz, 1H), 7.43 (d, J¼4.9 Hz, 1H), 7.49 (t, J¼7.6 Hz,
1H), 7.91 (d, J¼8.0 Hz, 1H), 8.02 (d, J¼7.9 Hz, 1H) ppm. 13C NMR
(100 MHz, DMSO-d6):
d
¼165.5, 152.5, 139.3, 134.8, 127.7, 126.8,
126.4, 126.3, 124.6, 121.8, 121.2, 31.4 ppm. HRMS (ESI): calcd for
C
12H10NS3: [MþH]þ 263.9975, found: 263.9972.
4.7. 2-((Benzo[d][1,3]dioxol-5-ylmethyl)thio)benzo[d]thiazole
(3af)
White solid (217.0 mg, yield 72%). Mp 55.4e56.7 ꢁC. IR (KBr):
4.1.4. Typical procedure for reuse of ionic liquid (f). At the end of the
reaction, 10 ml of deionized water were added into the reaction
mixture, the reaction mixture was extracted with ethyl acetate
(3ꢂ5 ml), the ionic liquid left in the water layer was concentrated
and dried under vacuum at 80 ꢁC for 8 h to eliminate any water
trapped from moisture and reused for another cycle.
n
¼3446, 2901, 1606, 1492, 1453, 1237, 1033, 869, 732 cmꢀ1. 1H NMR
(400 MHz, DMSO-d6):
d
¼4.58 (s, 2H), 6.00 (s, 2H), 6.87 (d, J¼7.8 Hz,
1H), 6.99 (d, J¼7.9 Hz, 1H), 7.07 (s, 1H), 7.37 (t, J¼7.4 Hz, 1H), 7.48 (t,
J¼7.5 Hz, 1H), 7.89 (d, J¼8.0 Hz, 1H), 8.01 (d, J¼7.9 Hz, 1H) ppm. 13
C
NMR (100 MHz, DMSO-d6):
d¼166.1, 152.6, 147.3, 146.7, 134.7, 130.0,
126.3, 122.5, 121.7, 121.1, 109.3, 108.1, 101.1, 36.8 ppm. HRMS (ESI):
calcd for C15H12NO2S2: [MþH]þ 302.0309, found: 302.0310.
4.2. 2-((4-Methoxybenzyl)thio)benzo[d]thiazole (3aa)
4.8. 2-(1-Ferrocenylethylthio)-benzo[d]thiazole (3ag)
White solid (261.5 mg, 91%). Mp 66.0e67.9 ꢁC. IR (KBr):
2922, 2836, 1597, 1513, 1433, 1244, 1176, 1035, 821, 755 cmꢀ1
NMR (400 MHz, DMSO-d6):
¼3.73 (s, 3H), 4.60 (s, 2H), 6.90 (d,
n
¼3049,
.
1H
Orange solid (314.8 mg, yield 83%). Mp 112e113 ꢁC. IR (KBr):
d
n
¼3080, 2926,1458,1379, 1312,1262,1123, 1000, 749 cmꢀ1. 1H NMR
J¼8.0 Hz, 2H), 7.37 (t, J¼7.4 Hz, 1H), 7.42 (d, J¼8.0 Hz, 2H), 7.48 (t,
(300 MHz, CDCl3):
d
¼1.82 (d, J¼7.2 Hz, 3H), 4.06e4.51 (m, 10H),
J¼7.4 Hz, 1H), 7.89 (d, J¼7.9 Hz, 1H), 8.01 (d, J¼7.7 Hz, 1H) ppm. 13
C
7.11e7.26 (m, 3H), 7.40 (d, J¼7.2 Hz, 1H) ppm. 13C NMR (75 MHz,
NMR (100 MHz, DMSO-d6):
d
¼166.3,158.8,152.7,134.7,130.4,124.5,
CDCl3):
d¼140.3, 127.6, 126.4, 124.5, 121.5, 114.6, 86.3, 69.8, 69.6,
121.7, 121.2, 114.0, 55.0, 36.4 ppm. HRMS (ESI): calcd for
68.9, 68.7, 67.8, 67.2, 53.9 ppm. HRMS (EI): calcd for C19H17FeNS2:
[M]þ 379.0152, found: 379.0170.
C
15H14NOS2: [MþH]þ 288.0517, found: 288.0514.
4.3. 2-((3,4-Dimethoxybenzyl)thio)benzo[d]thiazole (3ab)
4.9. 5-Methoxy-2-((4-methoxybenzyl)thio)benzo[d]thiazole
(3ba)
White solid (266.6 mg, yield 84%). Mp 68.9e71.6 ꢁC. IR (KBr):
n
¼3470, 2936, 2810, 1592, 1436, 1244, 1141, 1005, 851, 741 cmꢀ1. 1H
White solid (203.1 mg, yield 64%). Mp 91e93 ꢁC. IR (KBr):
NMR (400 MHz, DMSO-d6):
d¼3.73 (s, 6H), 4.59 (s, 2H), 6.90 (d,
n
¼3464, 2936, 2828, 1589, 1413, 1239, 1019, 827, 746, 684 cmꢀ1. 1H

X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
1173
NMR (400 MHz, DMSO-d6):
d
¼3.73 (s, 3H), 3.84 (s, 3H), 4.58 (s, 2H),
4.16. N-(4-Methoxybenzyl)-2,4-dinitroaniline (3ha)
6.90 (d, J¼8.1 Hz, 2H), 7.00 (d, J¼8.7 Hz, 1H), 7.41 (d, J¼8.3 Hz, 2H),
7.44 (s, 1H), 7.86 (d, J¼8.7 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3):
Yellow solid (242.6 mg, yield 80%). Mp 104.4e105.3 ꢁC. IR (KBr):
¼3374, 2923, 1612, 1509, 1251, 1079, 915, 809, 709 cmꢀ1. 1H NMR
d
¼167.9, 159.4, 159.1, 154.6, 130.50, 128.1, 127.1, 121.3, 114.3, 114.1,
n
104.8, 55.8, 55.5, 37.6 ppm. HRMS (ESI): calcd for C16H16NO2S2:
(400 MHz, DMSO-d6):
d
¼3.73 (s, 3H), 4.67 (s, 2H), 6.91 (d, J¼8.3 Hz,
[MþH]þ 318.0622, found: 318.0631.
2H), 7.09 (d, J¼9.6 Hz, 1H), 7.33 (d, J¼8.3 Hz, 2H), 8.20 (d, J¼9.5 Hz,
1H), 8.86 (d, J¼2.0 Hz,1H), 9.33 (s, 1H, NH) ppm. 13C NMR (100 MHz,
4.10. N-(4-Methoxybenzyl)-4-nitrobenzenamine (3ca)
DMSO-d6):
d
¼158.6, 148.0, 134.9, 129.9, 129.0, 128.4, 124.5, 115.5,
114.0, 103.7, 55.0, 45.6 ppm. HRMS (ESI): calcd for C14H14N3O5:
Yellow solid (193.7 mg, yield 75%). Mp 146e147 ꢁC. IR (KBr):
[MþH]þ 326.0753, found: 326.0757.
n
¼3352, 1598, 1512, 1299, 1070, 816 cmꢀ1
.
1H NMR (300 MHz,
DMSO-d6):
d
¼3.73 (s, 3H), 4.33 (s, 2H), 6.67 (d, J¼9.0 Hz, 2H), 6.91
4.17. N-(4-Methoxybenzyl)-4-chlorobenzenamine (3ia)
(d, J¼7.1 Hz, 2H), 7.27 (d, J¼7.5 Hz, 2H), 7.77 (t, J¼5.9 Hz,1H), 7.97 (d,
J¼9.1 Hz, 2H) ppm. 13C NMR (75 MHz, DMSO-d6):
¼158.4, 154.4,
d
White solid (61.9 mg, yield 25%). Mp 84e85 ꢁC. IR (KBr):
2918, 1595, 1490, 1235, 815 cmꢀ1 1H NMR (400 MHz, CDCl3):
n
¼3407,
135.8, 130.3, 128.6, 126.2, 113.9, 111.2, 55.1, 45.3, 45.2 ppm. HRMS
(EI): calcd for C14H14N2O3: [M]þ 258.1004, found: 258.1008.
.
d
¼3.80 (s, 3H), 4.22 (s, 2H), 6.56 (d, J¼8.7 Hz, 2H), 6.88 (d, J¼8.5 Hz,
2H), 7.11 (d, J¼8.6 Hz, 2H), 7.27 (d, J¼7.8 Hz, 2H) ppm. 13C NMR
4.11. N,N-Bis(4-methoxybenzyl)-4-nitroaniline (3caa)
(100 MHz, CDCl3):
d¼159.2, 146.9, 131.1, 129.2, 128.9, 122.3, 114.3,
114.1, 55.5, 48.1 ppm. HRMS (EI): calcd for C14H14ClNO: [M]þ
247.0764, found: 247.0763.
Yellow solid. Mp 94e95 ꢁC. IR (KBr):
1342, 808 cmꢀ1. 1H NMR (300 MHz, DMSO-d6):
n
¼3404, 2915, 1620, 1517,
d
¼3.70 (s, 6H), 4.74
(s, 4H), 6.79 (d, J¼9.5 Hz, 2H), 6.89 (d, J¼8.6 Hz, 4H), 7.15 (d,
J¼8.5 Hz, 4H), 7.97 (d, J¼9.4 Hz, 2H) ppm. 13C NMR (75 MHz, DMSO-
4.18. N-(4-Methoxybenzyl)-4-methoxybenzenamine (3ja)
d6):
d
¼158.4, 153.4, 136.1, 128.9, 127.8, 125.8, 114.1, 111.5, 55.1, 55.0,
53.4 ppm. HRMS (EI): calcd for C22H22N2O4: [M]þ 378.1580, found:
378.1577.
White solid (24.3 mg, yield 10%). Mp 96e97 ꢁC. IR (KBr):
2942, 2834, 1603, 1511, 1245, 1028, 818 cmꢀ1 1H NMR (300 MHz,
CDCl3):
¼3.74 (s, 3H), 3.80 (s, 3H), 4.20 (s, 2H), 6.60 (d, J¼8.7 Hz,
2H), 6.78 (d, J¼8.7 Hz, 2H), 6.87 (d, J¼8.4 Hz, 2H), 7.29 (d, J¼8.3 Hz,
2H). 13C NMR (75 MHz, DMSO-d6):
n
¼3379,
.
d
4.12. N-(4-Methoxybenzyl)-3-nitrobenzenamine (3da)
d
¼159.0, 152.4, 142.6, 131.8,
Yellow solid (167.8 mg, yield 65%). Mp 97e98 ꢁC. IR (KBr):
129.0, 115.1, 114.4, 114.2, 77.2, 56.0, 55.5, 49.0 ppm. HRMS (EI): calcd
n
¼3404, 2915, 1620, 1517, 1342, 808 cmꢀ1
.
1H NMR (300 MHz,
for C15H17NO2: [M]þ 243.1259, found: 243.1259.
DMSO-d6):
d
¼3.70 (s, 3H), 4.24 (d, J¼4.1 Hz, 2H), 7.03e6.80 (m, 4H),
7.25e7.32 (m, 5H) ppm. 13C NMR (75 MHz, DMSO-d6):
d¼158.3,
149.7, 148.8, 129.9, 128.5, 118.5, 113.8, 109.9, 105.6, 55.0, 45.6 ppm.
HRMS (EI): calcd for C14H14N2O3: [M]þ 258.1004, found: 258.1003.
4.19. N-(4-Methoxybenzyl)benzo[d]thiazol-2-amine (3ka)
White solid (127.1 mg, yield 47%). Mp 172e174 ꢁC. IR (KBr):
4.13. N-(4-Methoxybenzyl)-2-nitrobenzenamine (3ea)
n
¼3205, 2925, 2835,1553,1445,1245, 830 cmꢀ1. 1H NMR (300 MHz,
DMSO-d6):
d
¼3.70 (s, 3H), 4.47 (s, 2H), 6.88 (d, J¼8.0 Hz, 2H), 6.98
Yellow solid (133.6 mg, yield 44%). Mp 95e97 ꢁC. IR (KBr):
(t, J¼7.4 Hz, 1H), 7.18 (d, J¼7.5 Hz, 1H), 7.28 (d, J¼7.9 Hz, 2H), 7.35 (d,
n
¼3382, 2941, 1604, 1498, 1350, 1019, 827 cmꢀ1. 1H NMR (300 MHz,
J¼7.6 Hz, 1H), 7.63 (d, J¼7.6 Hz, 1H), 8.40 (s, 1H, NH) ppm. 13C NMR
DMSO-d6):
d
¼3.69 (s, 3H), 4.51 (d, J¼5.5 Hz, 2H), 6.63 (t, J¼7.7 Hz,
(100 MHz, DMSO-d6):
d¼166.0, 158.4, 152.4, 130.8, 130.4, 128.8,
1H), 6.89 (t, J¼9.7 Hz, 3H), 7.28 (d, J¼8.1 Hz, 2H), 7.42 (t, J¼7.7 Hz,
125.5, 120.9, 118.1, 113.8, 55.1, 46.6 ppm. HRMS (EI): calcd for
15H14N2OS: [M]þ 270.0827, found: 270.0828.
1H), 8.04 (d, J¼8.6 Hz, 1H), 8.56 (t, J¼4.9 Hz, 1H, NH) ppm. 13C NMR
C
(100 MHz, DMSO-d6):
d¼158.4, 144.9, 136.4, 130.2, 126.2, 115.4,
115.0, 114.0, 113.6, 55.1, 55.0, 45.2 ppm. HRMS (EI): calcd for
C
14H14N2O3: [M]þ 258.1004, found: 258.1005.
4.20. 1-(4-Methoxybenzyl)-1H-benzo[d][1,2,3]triazole (3la)
White solid(146.0 mg, yield 61%). Mp 85e86 ꢁC. IR (KBr):
4.14. 4-(4-Methoxybenzylamino)benzonitrile (3fa)
n
¼2944, 1600, 1506, 1240, 1018, 830 cmꢀ1
.
1H NMR (300 MHz,
¼3.77 (s, 3H), 5.78 (s, 2H), 6.86 (d, J¼8.5 Hz, 2H), 7.25 (d,
White solid (178.7 mg, yield 75%). Mp 109e111 ꢁC. IR (KBr):
CDCl3):
d
¼3376, 2851, 2202, 1602, 1513, 820 cmꢀ1
.
1H NMR (300 MHz,
J¼9.9 Hz, 2H), 7.31e7.37 (m, 3H), 8.06 (d, J¼7.9 Hz, 1H) ppm. 13C
n
DMSO-d6):
d
¼3.72 (s, 3H), 4.25 (d, J¼5.0 Hz, 2H), 6.64 (d, J¼7.0 Hz,
NMR (100 MHz, CDCl3):
d
¼159.7, 146.3, 132.7, 129.1, 127.3, 126.8,
2H), 6.89 (d, J¼6.7 Hz, 2H), 7.26e7.21 (m, 3H), 7.42 (d, J¼7.0 Hz, 2H),
123.9, 119.9, 114.4, 109.9, 55.3, 51.8 ppm. HRMS (EI): calcd for
C
ppm. 13C NMR (100 MHz, DMSO-d6):
d
¼158.3, 152.1, 133.3, 130.7,
14H13N3O: [M]þ 239.1059, found: 239.1054.
128.5,120.6, 113.8, 112.1, 95.8, 55.1, 55.0, 45.2 ppm. HRMS (EI): calcd
for C15H14N2O: [M]þ 238.1106, found: 238.1106.
4.21. 4-Nitro-N-(2,3,4-trimethoxybenzyl)aniline (3cc)
4.15. 1-(4-(4-Methoxybenzylamino)phenyl)ethanone (3ga)
Yellow solid (267.4 mg, yield 84%). Mp 111.6e113.3 ꢁC. IR (KBr):
White solid (165.9 mg, yield 65%). Mp 116e117 ꢁC. IR (KBr):
n
¼3332, 2929, 1597, 1465, 1295, 1095, 808 cmꢀ1. 1H NMR (400 MHz,
n
¼3341, 2855, 1635, 1584, 1255, 817 cmꢀ1
.
1H NMR (300 MHz,
CDCl3):
d
¼3.86 (s, 3H), 3.88 (s, 3H), 3.94 (s, 3H), 4.35 (s, 2H), 6.58 (d,
DMSO-d6):
d
¼2.37 (s, 3H), 3.72 (s, 3H), 4.27 (s, 2H), 6.60 (d,
J¼9.1 Hz, 2H), 6.63 (d, J¼8.5 Hz, 1H), 6.95 (d, J¼8.5 Hz, 1H), 8.08 (d,
J¼8.6 Hz, 2H), 6.89 (d, J¼8.4 Hz, 2H), 7.26 (d, J¼8.0 Hz, 2H), 7.68 (d,
J¼9.1 Hz, 2H). 13C NMR (75 MHz, CDCl3):
¼153.9, 153.4, 152.0,
d
J¼8.6 Hz, 2H) ppm. 13C NMR (75 MHz, DMSO-d6):
d¼195.0, 158.2,
142.5, 138.1, 126.5, 123.5, 123.2, 111.4, 107.4, 61.3, 61.0, 56.2,
43.0 ppm. HRMS (ESI): calcd for C16H18N2NaO5: [MþNa]þ 341.1108,
found: 341.1108.
152.7, 131.1, 130.4, 128.4, 125.0, 113.8, 111.1, 55.0, 45.2, 25.9 ppm.
HRMS (EI): calcd for C16H17NO2: [M]þ 255.1259, found: 255.1266.

1174
X.-Q. Chu et al. / Tetrahedron 69 (2013) 1166e1174
4.22. N-(1-Ferrocenylethyl)-4-nitrobenzenamine (3cg)
10KJB150016), a Research Grant from the Innovation Project for
Graduate Student of Jiangsu Province (CX10B-033Z), Innovation
project for undergraduate student-state level (No. 101028514), and
Key Project in Science & Technology Innovation Cultivation Pro-
gram of Soochow University.
Orange solid (276.6 mg, yield 79%). Mp 110e112 ꢁC. IR (KBr):
n
¼3400, 3084, 2986,1593,1509,1455,1307, 1101, 821 cmꢀ1. 1H NMR
(300 MHz, CDCl3):
d
¼1.53 (d, J¼6.6 Hz, 3H), 4.06e4.19 (m, 9H),
4.40e4.44 (m, 1H), 6.54 (d, J¼6.0 Hz, 2H), 8.07 (d, J¼6.0 Hz, 2H). 13
C
NMR (75 MHz, CDCl3):
d¼152.7, 137.7, 126.9, 111.5, 91.8, 68.9, 68.5,
Supplementary data
68.2, 67.4, 66.3, 47.3, 20.7 ppm. HRMS (EI): calcd for C18H18FeN2O2:
[M]þ 350.0718, found: 350.0715.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2012.11.045.
4.23. N-Benzhydryl-4-nitroaniline (3ch)
Yellow solid (276.9 mg, yield 91%). Mp 169.3e171.2 ꢁC. IR (KBr):
References and notes
n
¼3395, 3076, 2915, 1591, 1498, 1306, 1097, 834, 740, 689 cmꢀ1. 1H
1. (a) Welton, T. Chem. Rev. 1999, 99, 2071e2083; (b) Wilkes, J. S. Green Chem.
2002, 4, 73e80; (c) Hallettand, J. P.; Welton, T. Chem. Rev. 2011, 111, 3508e3576.
2. (a) Chauvin, Y. L.; Mussmann, L.; Olivier, H. Angew. Chem., Int. Ed. 1996, 34,
2698e2700; (b) Wasserscheid, P.; Keim, W. Angew. Chem., Int. Ed. 2000, 39,
3772e3789; (c) Sheldon, R. Chem. Commun. 2001, 2399e2407; (d) Li, D. M.; Shi,
F.; Peng, J. J.; Guo, S.; Deng, Y. Q. J. Org. Chem. 2004, 69, 3582e3585; (e)
Geldbach, T. J.; Zhao, D. B.; Castillo, N. C.; Laurenczy, G.; Weyershausen, B.;
Dyson, P. J. J. Am. Chem. Soc. 2006, 128, 9773e9780; (f) Jiang, T.; Ma, X.; Zhou, Y.;
Liang, S.; Zhang, J.; Han, B. Green Chem. 2008, 10, 465e469; (g) Sharma, Y. O.;
Degani, M. S. Green Chem. 2009, 11, 526e530.
NMR (400 MHz, CDCl3):
d
¼5.00 (s, 1H), 5.62 (s, 1H), 6.50 (d,
J¼9.1 Hz, 2H), 7.40e7.27 (m, 10H), 8.02 (d, J¼9.1 Hz, 2H). 13C NMR
(100 MHz, CDCl3):
d
¼152.3, 141.3, 138.4, 129.2, 128.12, 127.5, 126.3,
112.3, 62.5 ppm. HRMS (ESI): calcd for C19H17N2O2: [MþH]þ
305.1290, found: 305.1278.
4.24. 3-(4-Methoxybenzyl)-1H-indole (3ma)
3. Doherty, S.; Goodrich, P.; Hardacre, C.; Luo, H. K.; Rooney, D. W.; Seddon, K. R.;
Styring, P. Green Chem. 2004, 6, 63e67.
. Pale yellow solid (149.5 mg, yield 63%). Mp 80e82 ꢁC. 1H NMR
4. (a) Song, C. E.; Shim, W. H.; Roh, E. J.; Choo, J. H. Chem. Commun. 2000,
1695e1696; (b) Wasserscheid, P.; Sesing, M.; Korth, W. Green Chem. 2002, 4,
134e138.
5. (a) Fraga-Dubreuil, J.; Bourahla, K.; Rahmouni, M.; Bazureau, J. P.; Hamelin, J.
Catal. Commun. 2002, 3, 185e190; (b) Bradaric, C. J.; Downard, A.; Kennedy, C.;
Rovertson, A. J.; Zhou, Y. H. Green Chem. 2003, 5, 143e152; (c) Alleti, R.; Oh, W.
S.; Perambuduru, M.; Afrasiabi, Z.; Simm, E.; Reddy, V. P. Green Chem. 2005, 7,
203e206.
(300 MHz, CDCl3):
d
¼3.77 (s, 3H), 4.05 (s, 2H), 6.82 (d, J¼8.6 Hz,
2H), 6.88 (s, 1H), 7.06 (dd, J¼14.7, 7.7 Hz, 2H), 7.18 (t, J¼8.5 Hz, 3H),
7.34 (d, J¼8.1 Hz, 1H), 7.51 (d, J¼7.8 Hz, 1H), 7.91 (s, 1H) ppm. 13
C
NMR (75 MHz, CDCl3):
d
¼152.56, 131.31, 128.15, 124.43, 122.21,
117.07, 116.85, 114.15,114.01, 111.11, 108.58, 105.91, 50.12, 25.55 ppm.
HRMS (EI): calcd for C16H15NO: [M]þ 237.1154, found: 237.1153.
6. (a) Wang, Y.; Li, H.; Wang, C.; Jiang, H. Chem. Commun. 2004, 1938e1939; (b)
Wang, C.; Guo, P.; Li, H.; Wang, Y.; Weng, J.; Wu, L. Green Chem. 2006, 8,
603e607.
4.25. 5-Bromo-3-(4-methoxybenzyl)-1H-indole (3na)
7. (a) Zhang, L.; Xian, M.; He, Y.; Li, L.; Yang, J.; Yu, S.; Xu, X. Bioresour. Technol.
2009, 100, 4368e4373; (b) Han, F.; Yang, L.; Li, Z.; Xia, C. G. Org. Biomol. Chem.
2012, 10, 346e354.
8. (a) Wilkes, J. S. J. Mol. Catal. A: Chem. 2004, 214, 11e17; (b) Fang, D.; Zhou, X.; Ye,
Z.; Liu, Z. Ind. Eng. Chem. Res. 2006, 45, 7982e7984; (c) Santra, S.; Majee, A.;
Hajr, A. Tetrahedron Lett. 2011, 52, 3825e3827; (d) Han, F.; Yang, L.; Li, Z.; Xia, C.
G. Adv. Synth. Catal. 2012, 354, 1052e1060.
White solid (246.6 mg, yield 78%). Mp 76e78 ꢁC. 1H NMR
(300 MHz, CDCl3):
d
¼3.79 (s, 3H), 4.01 (s, 2H), 6.84 (d, J¼8.5 Hz,
2H), 6.91 (s,1H), 7.18 (d, J¼8.6 Hz, 2H), 7.22 (d, J¼8.5 Hz,1H), 7.27 (d,
J¼8.5 Hz, 1H), 7.64 (s, 1H), 7.98 (s, 1H) ppm. 13C NMR (100 MHz,
CDCl3):
d
¼158.31, 135.52, 133.16, 129.94, 125.30, 123.90, 122.20,
9. Bovet, D. Ann. N.Y. Acad. Sci. 1950, 1089e1226.
118.97, 116.45, 114.95, 114.26, 112.96, 55.73, 30.92 ppm. HRMS (EI):
calcd for C16H14BrNO: [M]þ 315.0259, found: 315.0260.
€
€
10. Talaz, O.; Gulcin, I.; Goksu, S.; Saracoglu, N. Bioorg. Med. Chem. 2009, 17,
6583e6589.
11. (a) Poon, K. W. C.; House, S. E.; Dudley, G. B. Synlett 2005, 3142e3144; (b) Long,
T. R.; Maity, P. K.; Samarakoon, T. B.; Hanson, P. R. Org. Lett. 2010, 12, 2904e2907.
12. (a) Trost, B. M. Science 1991, 254, 1471e1477; (b) Salvatore, R. N.; Yoon, C. H.;
Jung, K. W. Tetrahedron 2001, 57, 7785e7855; (c) Wuts, P. G. M.; Greene, T. W.
Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York,
NY, 2007; (d) Suzuki, K.; Hori, Y.; Kobayashi, T. Adv. Synth. Catal. 2008, 350,
652e656; (e) Meshram, H. M.; Reddy, B. C.; Goud, P. R. Synth. Commun. 2009,
39, 2297e2303.
4.26. 3-(4-Methoxybenzyl)-5-methyl-1H-indole (3oa)
Brown solid (118.1 mg, yield 47%). Mp 74e76 ꢁC. 1H NMR
(300 MHz, CDCl3):
d
¼2.42 (s, 3H), 3.78 (s, 3H), 4.02 (s, 2H),
6.88e6.78 (m, 3H), 7.00 (d, J¼8.3 Hz, 1H), 7.19 (d, J¼7.7 Hz, 2H), 7.23
(s, 1H), 7.30 (s, 1H), 7.83 (s, 1H) ppm. 13C NMR (75 MHz, CDCl3):
13. (a) Luzung, M. R.; Toste, F. D. J. Am. Chem. Soc. 2003, 125, 15760e15761; (b)
Kinoshita, H.; Shinokubo, H.; Oshima, K. Org. Lett. 2004, 6, 4085e4088; (c)
Hamid, M. H. S. A.; Slatford, P. A.; Williams, J. M. J. Adv. Synth. Catal. 2007, 349,
1555e1575; (d) Hamid, M. H. S. A.; Allen, C. L.; Lamb, G. W.; Maxwell, A. C.;
Maytum, H. C.; Watson, A. J. A.; Williams, J. M. J. J. Am. Chem. Soc. 2009, 131,
1766e1774; (e) Dobereiner, G. E.; Crabtree, R. H. Chem. Rev. 2010, 110, 681e703;
(f) Pingen, D.; Kller, C. M.; Vogt, D. Angew. Chem., Int. Ed. 2010, 49, 8130e8133;
d
¼157.61, 135.02, 133.69, 129.81, 128.75, 127.90, 123.86, 122.70,
118.97, 115.90, 113.97, 111.26, 55.52, 30.88, 21.81 ppm. HRMS (EI):
calcd for C17H17NO: [M]þ 251.1310, found: 251.1311.
4.27. 5-Methoxy-3-(4-methoxybenzyl)-1H-indole (3pa)
€
(g) Imm, S.; Bahn, S.; Neubert, L.; Neumann, H.; Beller, M. Angew. Chem., Int. Ed.
2010, 49, 8126e8127.
White solid (165.7 mg, yield 62%). Mp 97e99 ꢁC. 1H NMR
14. Bisaro, F.; Prestat, G.; Vitale, M.; Poli, G. Synlett 2002, 1823e1826.
15. Yasuda, M.; Somyo, T.; Baba, A. Angew. Chem., Int. Ed. 2006, 45, 793e796.
16. Rueping, M.; Nachtsheim, B. J.; Kuenkei, A. Org. Lett. 2007, 9, 825e827.
17. (a) Motokura, K.; Fujita, N.; Mori, K.; Mizugaki, T.; Ebitani, K.; Kaneda, K. Angew.
Chem., Int. Ed. 2006, 45, 2605e2609; (b) Motokura, K.; Nakagiri, N.; Mizugaki, T.;
Ebitani, K.; Kaneda, K. J. Org. Chem. 2007, 72, 6006e6015.
18. Sanz, R.; Martinez, A.; Miguel, D.; Alvarez-Gutierrez, J. M.; Rodriguez, F. Adv.
Synth. Catal. 2006, 348, 1841e1845.
19. Sanz, R.; Miguel, D.; Martinez, A.; Alvarez-Gutierrez, J. M.; Rodriguez, F. Org.
(300 MHz, CDCl3):
J¼9.7 Hz, 4H), 6.95 (s, 1H), 7.23e7.18 (m, 2H), 7.25 (s, 1H), 7.83 (s,
1H) ppm. 13C NMR (100 MHz, CDCl3):
d
¼3.78 (s, 3H), 3.81 (s, 3H), 4.02 (s, 2H), 6.84 (t,
d¼158.10, 154.16, 133.55,
131.93, 129.91, 128.12, 123.44, 116.25, 114.06, 112.39, 112.12, 101.33,
56.22, 55.61, 30.89 ppm. HRMS (EI): calcd for C17H17NO2: [M]þ
267.1259, found: 267.1256.
Lett. 2007, 9, 2027e2030.
20. (a) Hajipour, A. R.; Rajaei, A.; Ruoho, A. E. Tetrahedron Lett. 2009, 50, 708e711;
(b) Funabiki, K.; Komeda, T. Tetrahedron 2009, 65, 7457e7463; (c) Liu, L. Y.; Li, J.
Tetrahedron Lett. 2011, 52, 5636e5639.
Acknowledgements
21. Shen, Z.-L.; Ji, S.-J.; Loh, T.-P. Tetrahedron Lett. 2005, 46, 3137e3139.
22. (a) Gu, D.-G.; Ji, S.-J. Chin. J. Chem. 2008, 26, 578e582; (b) Gu, D.-G.; Ji, S.-J.;
Jiang, Z.-Q.; Zhou, M.-F.; Loh, T.-P. Synlett 2005, 959e962.
The work was partially supported by the National Natural Sci-
ence Foundation of China (No. 21042007, 21172162), Natural Sci-
ence Basic Research of Jiangsu Province for Higher Education (No.
23. Kondo, T.; Mitsudo, T.-A. Chem. Rev. 2000, 100, 3205e3220.