Recyclable [Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system for oxidative annulation of alkynes by aniline derivatives: Green synthesis of indoles

Article abstract of DOI:10.1016/j.tet.2017.01.023

[Ru₂Cl₃(p-cymene)₂][PF₆] in a mixture of PEG-400 and water is shown to be a highly efficient catalyst for the oxidative annulation of alkynes by N-2-pyrimidyl-substituted anilines bearing a removable directing g

Full text of DOI:10.1016/j.tet.2017.01.023

Accepted Manuscript
Recyclable [Ru Cl (p-cymene) ][PF ]/Cu(OAc) /PEG-400/H O system for oxidative
2 3
2
6
2
2
annulation of alkynes by aniline derivatives: Green synthesis of indoles
Yang Liao, Ting Wei, Tao Yan, Mingzhong Cai
PII:
S0040-4020(17)30036-4
10.1016/j.tet.2017.01.023
TET 28393
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 10 December 2016
Revised Date: 8 January 2017
Accepted Date: 9 January 2017
Please cite this article as: Liao Y, Wei T, Yan T, Cai M, Recyclable [Ru Cl (p-cymene) ][PF ]/
2 3
2
6
Cu(OAc) /PEG-400/H O system for oxidative annulation of alkynes by aniline derivatives: Green
2
2
synthesis of indoles, Tetrahedron (2017), doi: 10.1016/j.tet.2017.01.023.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Recyclable
[Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/
H2O system for oxidative annulation of alkynes by aniline
derivatives: Green synthesis of indoles
Yang Liao, Ting Wei, Tao Yan, Mingzhong Cai*
R1
R1
[Ru2Cl3(p-cymene)2][PF6]
R
R2
(3 mol%)
R
+
.
NH
N
Cu(OAc)2 H2O (2.0 equiv)
PEG-400/H2O (3:2),100 oC
N
R2
N
N
N
Both Ru and Cu are recyclable!
28 examples
up to 96% yield

ACCEPTED MANUSCRIPT
Recyclable [Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/
H2O system for oxidative annulation of alkynes by aniline
derivatives: Green synthesis of indoles
Yang Liao, Ting Wei, Tao Yan and Mingzhong Cai*
Key Laboratory of Functional Small Organic Molecule, Ministry of Education and
College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang
330022, P. R. China
Fax: (+86)-791-8812-0388; E-mail: mzcai@jxnu.edu.cn
ABSTRACT
[Ru2Cl3(p-cymene)2][PF6] in a mixture of PEG-400 and water is shown to be a highly
efficient catalyst for the oxidative annulation of alkynes by N-2-pyrimidyl-substituted
anilines bearing a removable directing group. The reaction could be conducted at
100 °C using Cu(OAc)2·H2O (2.0 equiv) as oxidant, yielding a variety of indole
derivatives in good to excellent yields. The isolation of the products was readily
performed by extraction with petroleum ether and more importantly, both
[Ru2Cl3(p-cymene)2][PF6] and Cu(OAc)2 in PEG-400/H2O system could be easily
recycled and reused six times without any loss of catalytic activity.
Keywords: Ruthenium; Recycling; Oxidative annulation; Indole; Green chemistry.
1. Introduction
The indole nucleus is one of the most ubiquitous moieties present in many biologi-
cally significant natural products as well as pharmaceuticals and agrochemicals.1
Therefore, many efficient methods for their synthesis have been developed,2 one of
the most commonly used methods is the Fischer-type indole synthesis.3 In addition,
transition-metal-catalyzed cross-coupling reactions and cyclizations have emerged as
powerful tools for the selective assembly of indole derivatives.4 Numerous transition-
metal-catalyzed syntheses of indoles such as cyclization of o-alkynylanilines,5 annula-
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tion of ortho-halo-substituted anilines with alkynes,6 reductive cyclization of ortho-
substituted nitroarenes,7 and other coupling/condensation tandem reactions,8 have
been reported in recent years. Very recently, Gu et al. reported the synthesis of indole
derivatives via copper-catalyzed [4+2] annulation of 2-butoxy-2,3-dihydrofurans with
pyrroles.9 Both Hegedus indole synthesis and Larock’s annulation have proven parti-
cularly useful for the construction of indoles.10 However, most of these methods still
suffer from limited availability or high cost of starting materials due to the use of pre-
functionalized starting materials, which reduces the overall atom and step economy.
Recently, transition-metal-catalyzed C–H bond activation (CHA) has provided an
alternative tool for the synthesis of heterocycles,11 and several indole syntheses using
a C–H bond activation strategy have been reported. Stuart et al. reported an elegant
Rh(III)-catalyzed oxidative annulation of internal alkynes by acetanilides leading to
N-protected indoles.12 Takemoto and co-workers described an efficient synthesis of
indoles via Pd(OAc)2-catalyzed benzylic C–H bond activation and insertion into
isocyanides.13 Catalytic dehydrogenative cross-coupling reactions have also proven
useful synthetic tools for indole derivatives.14 Afterward, Rh-, Pd-, and Ru-catalyzed
C–H bond activation under oxidative or redox-neutral conditions were extensively
explored for the synthesis of indoles.15 Despite these significant advances, industrial
applications of these homogeneous palladium, rhodium, and ruthenium complexes
remain a challenge because they are expensive, cannot be recycled, and difficult to be
separated from the product mixture. These problems are of particular environmental
and economic concerns in industry, especially the pharmaceutical industry. Therefore,
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from the standpoint of green and sustainable chemistry,16 the development of a recyc-
lable and reusable catalyst system that allows for highly efficient and green synthesis
of indoles via C–H activation/cyclization strategy is worthwhile.
Development of recyclable catalytic systems for transition-metal-catalyzed organic
transformations has become a task of great economic and environmental importance
in chemical and pharmaceutical industries, especially when expensive and/or toxic
heavy metal complexes are employed. In order to gratify both recyclability and
environmental concerns, a simple and efficient method is to immobilize the catalyst in
a liquid phase by dissolving it into a nonvolatile and nonmixing liquid, such as ionic
liquids17 and PEGs.18 However, ionic liquids provide some disadvantages, such as a
complicated method for the preparation of ionic liquids as well as their environmental
safety is still debated since the toxicity and environmental burden data are unknown
for the most of them. It is well documented that poly(ethylene glycols) (PEGs) are
commercially easily available and inexpensive, thermally stable, recoverable, biode-
gradable and nontoxic compounds which serve as efficient media for environmentally
friendly and safe chemical reactions.19 Recently, PEGs have been widely utilized as
reaction media for the Pd-catalyzed carbon-carbon bond formation reactions such as
Heck coupling,18a,b Suzuki coupling,18c,d the homocoupling and cross-coupling of aryl
halides,18e the direct arylation of 1,2,3-triazoles with aryl bromides,18f and carbony-
lative Suzuki18g or Sonogashira18h cross-couplings with facile recyclability of solvents
and palladium catalysts. Some organic transformations catalyzed by other transition
metals in PEGs have also been described, including catalysis by Ru,20 Pt,21 Ni22 and
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Cu23 in recent years. However, to the best of our knowledge, the ruthenium-catalyzed
oxidative C–H/N–H bond functionalizations of anilines with a removable directing
group in PEGs have not been reported until now. We herein report the application of
[Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system as a highly efficient and
reusable catalytic medium for the oxidative annulation of alkynes by N-2-pyrimidyl-
substituted anilines leading to a variety of indole derivatives in good to excellent
yields (Scheme 1).
Scheme 1. Synthesis of indole derivatives by Ru-catalyzed oxidative annulation of
alkynes by N-2-pyrimidyl-substituted anilines in PEG-400/H2O.
2. Results and discussion
Initially, we focused our optimization investigations on the use of N-2-pyrimidyl-
substituted anilines since the 2-pyrimidyl group has proven to be easily removed from
the indole nucleus.24 The oxidative annulation of 2-methyl-N-(2-pyrimidyl)aniline 1a
with diphenylacetylene 2a was chosen as a model reaction to determine the optimum
conditions and the results are summarized in Table 1. At first, the solvent effect was
examined by using [Ru2Cl3(p-cymene)2][PF6] complex as catalyst and Cu(OAc)2·H2O
as oxidant, and a significant solvent effect was observed. When PEG-400 was used as
solvent, the reaction proceeded slowly and the desired product 3a was obtained in
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only 53% yield (Table 1, entry 1). To our delight, the use of a mixture of PEG-400
and H2O as solvent could improve the yield of the product 3a obviously (Table 1,
entries 2-6). The reaction run in PEG-400/H2O (3:2) gave 3a in 93% yield (Table 1,
entry 3). Our next studies focused on the effect of oxidant on the model reaction.
When benzoquinone, PhI(OAc)2, AgNO3 and CuBr2 were used as the oxidant, no
reaction was observed, whereas AgOAc afforded low yield (Table 1, entries 7-11). In
addition, PEG-600 and PEG-1000 were also tested at the same reaction conditions to
examine the efficiency of various chain length PEGs on the reaction, PEG-400 was
superior to PEG-600 and PEG-1000 (Table 1, entries 12-15). It was found that the
reaction was completed when it was performed in PEG-400/H2O (3:2) at 100 °C for
24 h. Lowering reaction temperature to 80 °C resulted in a significant decrease in
yield (Table 1, entry 16). When [RuCl2(p-cymene)]2 (3.0 mol%) was used as catalyst,
low catalytic efficacy was observed due to the absence of a weakly coordination
anion25 (Table 1, entry 17). Therefore, the optimal catalytic system involved the use of
[Ru2Cl3(p-cymene)2][PF6] (3.0 mol%), Cu(OAc)2·H2O (2.0 equiv) in PEG-400/H2O
(v/v = 3:2) at 100 °C under Ar for 24 h (Table 1, entry 3).
Table 1 Optimization of ruthenium-catalyzed oxidative annulation of 2-methyl-
N-(2-pyrimidyl)aniline with diphenylacetylene.a
Entry
1
Solvent (v/v)
Oxidant
Time (h)
Yield (%)b
53
PEG-400
Cu(OAc)2·H2O 36
5

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2
3
PEG-400/H2O (3:1)
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 24
72
93
90
92
89
0
PEG-400/H2O (3:2)
PEG-400/H2O (1:1)
PEG-400/H2O (2:3)
PEG-400/H2O (1:3)
PEG-400/H2O (3:2)
PEG-400/H2O (3:2)
PEG-400/H2O (3:2)
PEG-400/H2O (3:2)
PEG-400/H2O (3:2)
PEG-600
4
5
6
7
benzoquinone
PhI(OAc)2
AgNO3
36
36
36
36
36
8
0
9
0
10
11
12
13
14
15
16c
17d
AgOAc
12
0
CuBr2
Cu(OAc)2·H2O 36
Cu(OAc)2·H2O 36
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 24
Cu(OAc)2·H2O 36
Cu(OAc)2·H2O 48
48
39
90
81
61
9
PEG-1000
PEG-600/H2O (3:2)
PEG-1000/H2O (3:2)
PEG-400/H2O (3:2)
PEG-400/H2O (3:2)
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), [Ru2Cl3(p-cymene)2][PF6] (3.0 mol%),
b
c
d
oxidant (2.0 equiv), solvent (2.0 mL), 100 ºC, under Ar. Isolated yield. At 80 ºC.
[RuCl2(p-cymene)]2 (3.0 mol%) was used.
With the optimized conditions established, we tried to investigate the scope of this
Ru(II)-catalyzed oxidative annulation reactions in PEG-400/H2O. Firstly, annulation
reactions of 2-methyl-N-(2-pyrimidyl)aniline 1a with various alkynes were examined
and the results are summarized in Table 2. As shown in Table 2, it is evident that most
of the Ru(II)-catalyzed oxidative annulation reactions proceeded smoothly under the
optimized reaction conditions, affording good to excellent yields of indole derivatives.
The [Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system was not limited to
diphenylacetylene derivatives, but also allowed the efficient annulation of alkyl-sub-
stituted internal alkynes. For example, the reaction of 2-methyl-N-(2-pyrimidyl)ani-
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line 1a with hex-3-yne gave the desired 2,3-diethyl-7-methyl-1-(pyrimidin-2-yl)-1H-
indole 3b in 63% yield. Moreover, alkyl and aryl-substituted internal alkynes were
converted into the corresponding indole derivatives with high regioselectivity, placing
the aromatic substituents adjacent to the nitrogen. The reactions of alkyl and phenyl-
substituted alkynes afforded the desired products 3c-3e in excellent yields and no
regioisomer was observed. When alkyl and aryl-substituted alkynes with electron-
donating or electron-withdrawing subsitituents were used as substrates, the corres-
ponding products 3f-3i were also obtained in good yields (61-83%). The results
indicated that the electronic nature of substituents on the benzene ring has limited
influence on the reaction and both electron-donating and electron-withdrawing groups
were tolerated well.
Table 2 Ruthenium-catalyzed oxidative annulation of various alkynes by 2-methyl-
N-(2-pyrimidyl)aniline.a,b
Ph
Et
Me
Bu-n
Ph
Et
Ph
Ph
Ph
Et
N
N
N
N
N
N
N
N
N
N
Me
Me
Me
Me
Me
N
N
N
N
N
3a, 93%
3d, 94%
3e, 93%
Bu-n
3b, 63%
3c, 92%
Bu-n
Bu-n
Bu-n
OMe
OH
COMe
CHO
N
N
N
N
N
N
N
N
Me
N
Me
3g, 64%
Me
3h, 81%
Me
3i, 61%
N
N
N
3f, 83%
a
Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), [Ru2Cl3(p-cymene)2][PF6] (3.0 mol%),
7

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b
Cu(OAc)2·H2O (1.0 mmol), PEG-400 (1.2 mL), H2O (0.8 mL), 100 ºC, 24 h, under Ar. Isolated
yield.
Encouraged by the above results, reactions of different N-2-pyrimidyl-substituted
anilines with internal alkynes were then examined and the results are listed in Table 3.
The reactions of 2-methoxy-N-(2-pyrimidyl)aniline bearing a strong electron-donating
group with various internal alkynes proceeded smoothly, affording the expected
products 3j-3o in good to excellent yields (73-96%). The reaction of 2-trifluoromethyl
-N-(2-pyrimidyl)aniline bearing a strong electron-withdrawing group with tolane gave
the desired indole 3p in 88% yield. 2,4-Disubstituted aniline derivatives such as 2,4-
dimethyl-N-(2-pyrimidyl)aniline and bulky N-(naphthalene-1-yl)pyrimidin-2-amine
were also good substrates under the optimized conditions and underwent the oxidative
annulation reactions with different alkynes effectively, furnishing the desired products
3q-3z in good to excellent yields (64-92%). Notably, a meta-substituted aniline,
3-methyl-N-(2-pyrimidyl)aniline could undergo the site-selective functionalization at
the less sterically hindered C–H bond, and the reactions with alkynes afforded the
expected products 3a' and 3b' as the sole product. Generally, the [Ru2Cl3(p-cymene)2]
[PF6]/Cu(OAc)2/PEG-400/H2O system proved to be widely applicable since a range
of valuable functional groups such as methyl, methoxy, trifluoromethyl, hydroxy,
ketone and aldehyde were tolerated well. We have also performed the removal of
directing group in the desired products 3.24 The treatment of 7-methyl-2,3-diphenyl-
1-(pyrimidin-2-yl)-1H-indole (3a) with NaOEt in DMSO at 120 ºC for 24 h afforded
7-methyl-2,3-diphenyl-1H-indole (4a) in 91% yield (Scheme 2).
8

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Table 3 Scope of ruthenium-catalyzed synthesis of indole derivatives by oxidative
annulation.a,b
a
Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), [Ru2Cl3(p-cymene)2][PF6] (3.0 mol%),
b
Cu(OAc)2·H2O (1.0 mmol), PEG-400 (1.2 mL), H2O (0.8 mL), 100 ºC, 24 h, under Ar. Isolated
yield.
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Ph
Ph
Ph
NaOEt
Ph
N
DMSO, 120 oC, 24 h
N
N
H
Me
N
Me
3a
4a 91%
Scheme 2. Synthesis of 7-methyl-2,3-diphenyl-1H-indole (4a)
A plausible mechanism for the ruthenium-catalyzed oxidative annulation of alkyne
2 with N-2-pyrimidyl-substituted aniline 1 is showed in Scheme 3.15d First, the reac-
tion of [Ru2Cl3(p-cymene)2][PF6] with acetate generates in situ ruthenium(II) acetate
complex A. Reversible coordination of the pyrimidyl nitrogen of aniline 1 to the
ruthenium(II) acetate complex A and subsequent ortho-C–H bond ruthenation with
liberation of AcOH gives a six-membered ruthenacycle C as a key intermediate. Then
ruthenacycle intermediate C undergoes coordination and migratory insertion with
alkyne 2 to produce a ruthenacycle intermediate D. Finally, reductive elimination of
intermediate D affords the desired product 3, and the resulting [Ru(0)] species may be
oxidized in the presence of Cu(OAc)2 to regenerate ruthenium(II) acetate complex A.
To examine the reusability of the solvent, the catalyst as well as the oxidant, the
oxidative annulation reaction of 2-methoxy-N-(2-pyrimidyl)aniline (0.5 mmol) with
diphenylacetylene (1.0 mmol) was evaluated in the presence of [Ru2Cl3(p-cymene)2]
[PF6] (3.0 mol%) and Cu(OAc)2·H2O (1.0 mmol) in PEG-400/H2O (3:2, 2.0 mL) at
100 ºC for 24 h. As demonstrated in Fig. 1, we were pleased to observe that the
[Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system could be recycled and
reused six times without any loss of catalytic activity. After initial experimentation,
the reaction mixture was extracted with light petroleum ether for three times and the
10

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[Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system was then subjected to a
second run of the reaction by charging with the same substrates (2-methoxy-N-(2-
pyrimidyl)aniline and diphenylacetylene) without the addition of [Ru2Cl3(p-cymene)2]
[PF6] and Cu(OAc)2·H2O. The results of six runs showed that they were almost con-
sistent in yields within an average reaction time of 26 h (96%, 94%, 96%, 95%, 95%,
and 94%, respectively).
R2
[Ru2Cl3(p-cymene)2][PF6]
R1
N
OAc
i-Pr
H
N
N
N
Me
N
H
1
N
3
O
Ru
2 CuOAc + 2 OAc
Me
O
(A)
2 Cu(OAc)2
Me
i-Pr
Me
i-Pr
R1
O
Ru
Ru
Me
pym
N
2-
N
O
N
R2
NHPh
(B)
(D)
Me
i-Pr
HOAc
Ru
R1
R2
N
OAc
HOAc
2
N
N
H
(C)
Scheme 3. Proposed catalytic cycle.
Recently, Kantam et al. described the synthesis of N-(2-pyridyl)indoles and N-(2-
pyrimidyl)indoles via the oxidative annulation of N-aryl-2-aminopyridines or N-aryl-
11

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2-aminopyrimidines with alkynes in DMF by using a nanocrystalline magnesium
oxide-supported palladium nanoparticle [NAP-Mg-Pd(0)] as catalyst and CuCl2 (2
equiv.) as oxidant.26 Although good yields were achieved and the palladium(0)
catalyst could be recycled up to four cycles without significant loss of catalytic
activity, the procedure for preparing the heterogeneous palladium(0) catalyst was
rather complicated and CuCl2 (2 equiv.) as oxidant could not be recycled in DMF. In
contrast, in our catalytic system, both [Ru2Cl3(p-cymene)2][PF6] and Cu(OAc)2 in
PEG-400/H2O as a green solvent could be easily recycled for six times without any
loss of catalytic activity.
100
80
60
40
20
0
1
2
3
4
5
6
Reused times
Fig. 1. Recycle of the catalytic system.
3. Conclusion
In conclusion, a highly efficient, green and sustainable [Ru2Cl3(p-cymene)2][PF6]/
Cu(OAc)2/PEG-400/H2O system for oxidative annulation reaction of alkynes by N-2-
pyrimidylanilines has been developed. In the presence of [Ru2Cl3(p-cymene)2][PF6]
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(3.0 mol%), the oxidative annulation reactions of a variety of N-2-pyrimidyl-subs-
tituted anilines with various internal alkynes proceeded smoothly and efficiently at
100 °C using Cu(OAc)2·H2O (2.0 equiv) as oxidant in a mixture of PEG-400 and
water to furnish the corresponding indole derivatives in good to excellent yields.
Furthermore, the [Ru2Cl3(p-cymene)2][PF6]/Cu(OAc)2/PEG-400/H2O system could be
recycled and reused six times without any loss of catalytic activity. This protocol will
serve as an efficient, practical and green method for the synthesis of bioactive indoles
with ample scope. Currently, further efforts to extend the application of the system in
other ruthenium-catalyzed transformations are underway in our laboratory.
4. Experimental
4.1. Physical measurements and materials
All chemicals were reagent grade and used as purchased. [Ru2Cl3(p-cymene)2][PF6]
was prepared from [RuCl2(p-cymene)]2 and KPF6 according to a literature method.24a
N-2-Pyrimidyl-substituted anilines were synthesized from anilines and 2-chloro-
pyrimidine according to previously described method.27 The products were purified
by flash chromatography on silica gel. Mixture of EtOAc and light petroleum ether
was generally used as eluent. All products were characterized by comparison of their
spectra and physical data with authentic samples. The configurations of products 3c-3i,
1
3l-3o, 3s-3v and 3x-3z were confirmed by the NOESY in the H NMR spectra. IR
1
spectra were recorded on an FT-IR spectrometer. H and 13C NMR spectra were
recorded at 400 or 100 MHz with CDCl3 as the solvent and TMS as an internal
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standard. Chemical shifts are reported in δ (ppm) relative to TMS. HRMS spectra
were recorded on a Q-Tof spectrometer with micromass MS software using
electrospray ionization (ESI). Melting points are uncorrected.
4.2. General procedure for the ruthenium-catalyzed oxidative annulation
reaction in PEG-400/H2O.
A mixture of N-2-pyrimidyl-substituted aniline 1 (0.5 mmol), alkyne 2 (1.0 mmol),
Cu(OAc)2·H2O (1.0 mmol), [Ru2Cl3(p-cymene)2][PF6] (0.015 mmol) in PEG-400 (1.2
mL) and H2O (0.8 mL) was stirred at 100 °C under Ar for 24 h until complete
consumption of starting material as judged by TLC. After being cooled to room
temperature, the mixture was extracted three times with light petroleum ether (3 × 10
mL). The combined ether phase was concentrated under reduced pressure, and the
residue was purified by flash column chromatography on silica gel (light petroleum
ether–ethyl acetate) to afford the desired products 3.
The mixture of [Ru2Cl3(p-cymene)2][PF6], Cu(OAc)2·H2O, PEG-400 and H2O was
then subjected to a second run of the reaction by charging with the same substrates
(N-2-pyrimidyl-substituted aniline 1 and alkyne 2) under the same conditions without
further addition of [Ru2Cl3(p-cymene)2][PF6] and Cu(OAc)2·H2O.
4.2.1. 2,3-Diphenyl-7-methyl-1-(pyrimidin-2-yl)-1H-indole (3a). White solid, mp
1
150-151 °C. H NMR (400 MHz, CDCl3): δ = 8.58 (d, J = 4.8 Hz, 2H), 7.62 (d, J =
7.6 Hz, 1H), 7.35 (d, J = 7.2 Hz, 2H), 7.26 (t, J = 7.6 Hz, 2H), 7.20-6.97 (m, 9H),
1.93 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.8, 158.1, 138.0, 136.7, 134.7,
131.8, 131.2, 130.4, 128.8, 128.3, 127.9, 127.6, 126.3, 126.1, 121.7, 121.6, 119.9,
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118.1, 118.0, 19.5. IR (KBr, cm-1): 1557, 1416, 1264, 1233, 1143, 744, 699. HRMS
+
(EI) m/z calcd for C25H20N3 [M+H+] 362.1657, found 362.1659.
4.2.2. 2,3-Diethyl-7-methyl-1-(pyrimidin-2-yl)-1H-indole (3b). Colorless oil. 1H NMR
(400 MHz, CDCl3): δ = 8.77 (d, J = 4.8 Hz, 2H), 7.42 (d, J = 7.6 Hz, 1H), 7.17-7.13
(m, 1H), 7.07 (t, J = 7.4 Hz, 1H), 6.92 (d, J = 7.2 Hz, 1H), 2.79-2.68 (m, 4H), 1.90 (s,
3H), 1.26 (t, J = 7.6 Hz, 3H), 0.95 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ = 159.4, 158.4, 139.1, 136.2, 129.8, 124.9, 121.7, 120.8, 119.1, 116.3, 20.0, 18.3,
17.7, 15.7, 14.9. IR (film, cm-1): 2964, 1561, 1417, 1224, 1150, 1034, 782, 740.
+
HRMS (EI) m/z calcd for C17H20N3 [M+H+] 266.1657, found 266.1652.
4.2.3. 3,7-Dimethyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3c).15d White solid, mp
1
138-139 °C. H NMR (400 MHz, CDCl3): δ = 8.61 (d, J = 4.8 Hz, 2H), 7.49 (d, J =
8.0 Hz, 1H), 7.25-7.18 (m, 5H), 7.15-6.98 (m, 3H), 2.31 (s, 3H), 1.95 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ = 159.8, 158.0, 137.8, 136.6, 132.3, 130.5, 130.3, 127.9,
127.3, 125.8, 121.6, 120.9, 119.3, 117.1, 112.2, 19.7, 9.5. IR (KBr, cm-1): 1559, 1495,
1418, 1267, 1229, 1166, 1074, 918, 701. HRMS (EI) m/z calcd for C20H18N3 [M+H+]
+
300.1501, found 300.1509.
4.2.4. 3-Ethyl-7-methyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3d).15d White solid,
mp 163-164 °C. 1H NMR (400 MHz, CDCl3): δ = 8.58 (d, J = 4.8 Hz, 2H), 7.54 (d, J
= 8.0 Hz, 1H), 7.23-7.18 (m, 5H), 7.12 (t, J = 7.6 Hz, 1H), 7.05 (t, J = 4.8 Hz, 1H),
6.98 (d, J = 7.2 Hz, 1H), 2.74 (q, J = 7.6 Hz, 2H), 1.94 (s, 3H), 1.26 (t, J = 7.6 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ = 159.6, 158.0, 137.4, 136.6, 132.4, 130.5,
129.3, 127.9, 127.4, 125.7, 121.7, 120.9, 119.2, 118.6, 117.3, 19.8, 17.9, 15.7. IR
15

ACCEPTED MANUSCRIPT
(KBr, cm-1): 1557, 1415, 1345, 1266, 1227, 1164, 1059, 698. HRMS (EI) m/z calcd
+
for C21H20N3 [M+H+] 314.1657, found 314.1665.
4.2.5. 3-Butyl-7-methyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3e). White solid, mp
87-88 °C. 1H NMR (400 MHz, CDCl3): δ = 8.57 (t, J = 2.4 Hz, 2H), 7.54 (d, J = 7.6
Hz, 1H), 7.24-7.20 (m, 5H), 7.11 (t, J = 7.6 Hz, 1H), 7.02 (t, J = 4.8 Hz, 1H), 6.98 (d,
J = 7.2 Hz, 1H), 2.72 (t, J = 7.6 Hz, 2H), 1.94 (s, 3H), 1.67-1.60 (m, 2H), 1.35-1.28
13
(m, 2H), 0.83 (t, J = 7.4 Hz, 3H). C NMR (100 MHz, CDCl3): δ = 159.7, 158.0,
137.9, 136.5, 132.5, 130.6, 129.6, 127.9, 127.5, 125.7, 121.7, 120.9, 119.3, 117.5,
117.2, 33.1, 24.3, 22.8, 19.8, 14.0. IR (KBr, cm-1): 3069, 2959, 2867, 1608, 1415,
1175, 1000, 841, 725. HRMS (EI) m/z calcd for C23H23N3Na+ [M+Na+] 364.1790,
found 364.1780.
4.2.6. 3-Butyl-7-methyl-2-(4-methoxyphenyl)-1-(pyrimidin-2-yl)-1H-indole (3f).15d
1
White solid, mp 105-106 °C. H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 4.8 Hz,
2H), 7.52 (d, J = 7.6 Hz, 1H), 7.20-6.94 (m, 5H), 6.76 (d, J = 8.8 Hz, 2H), 3.73 (s,
3H), 2.71 (t, J = 7.8 Hz, 2H), 1.92 (s, 3H), 1.68-1.61 (m, 2H), 1.35-1.28 (m, 2H), 0.84
(t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.8, 158.9, 158.0, 137.7,
136.5, 131.8, 129.6, 125.4, 124.7, 121.6, 120.8, 119.2, 117.3, 116.9, 113.3, 55.1, 33.1,
24.4, 22.8, 19.7, 14.0. IR (KBr, cm-1): 1558, 1507, 1412, 1249, 1177, 1015, 834, 747.
HRMS (EI) m/z calcd for C24H25N3O+ [M+] 371.1998, found 371.1995.
4.2.7. 3-Butyl-7-methyl-2-(4-hydroxyphenyl)-1-(pyrimidin-2-yl)-1H-indole (3g).15d
1
White solid, mp 106-107 °C. H NMR (400 MHz, CDCl3): δ = 8.62 (d, J = 4.8 Hz,
2H), 7.50 (d, J = 7.6 Hz, 1H), 7.13-7.08 (m, 2H), 6.97-6.93 (m, 3H), 6.44 (d, J = 8.4
16

ACCEPTED MANUSCRIPT
Hz, 2H), 2.66 (t, J = 7.6 Hz, 2H), 1.90 (s, 3H), 1.63-1.57 (m, 2H), 1.33-1.24 (m, 2H),
0.83 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.6, 158.0, 155.6, 137.8,
136.4, 131.8, 129.6, 125.5, 123.9, 121.4, 120.9, 119.4, 117.3, 117.0, 114.9, 32.9, 24.3,
22.8, 19.6, 14.0. IR (KBr, cm-1): 3125, 2923, 1564, 1418, 1336, 1267, 1097, 737.
HRMS (EI) m/z calcd for C23H23N3O+ [M+] 357.1841, found 357.1833.
4.2.8. 3-Butyl-7-methyl-2-(4-acetylphenyl)-1-(pyrimidin-2-yl)-1H-indole (3h).15d
1
White solid, mp 111-113 °C. H NMR (400 MHz, CDCl3): δ = 8.63 (dd, J = 4.8, 1.2
Hz, 2H), 7.84 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 7.6 Hz, 1H), 7.33 (d, J = 7.2 Hz, 2H),
7.17-7.11 (m, 2H), 7.02 (d, J = 7.2 Hz, 1H), 2.75 (t, J = 7.6 Hz, 2H), 2.57 (s, 3H),
1.96 (s, 3H), 1.68-1.63 (m, 2H), 1.35-1.28 (m, 2H), 0.85 (t, J = 7.2 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ = 197.8, 159.4, 158.1, 137.6, 136.8, 136.4, 135.7, 130.5, 129.5,
127.9, 126.2, 121.8, 121.1, 119.4, 118.4, 117.6, 33.0, 26.6, 24.3, 22.8, 19.8, 13.9. IR
(KBr, cm-1): 2921, 1678, 1562, 1416, 1348, 1265, 1079, 854. HRMS (EI) m/z calcd
for C25H26N3O+ [M+H+] 384.2076, found 384.2081.
4.2.9. 4-(3-Butyl-7-methyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)benzaldehyde (3i). White
solid, mp 166-167 °C. 1H NMR (400 MHz, CDCl3): δ = 9.97 (s, 1H), 8.65 (d, J = 4.4
Hz, 2H), 7.76 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 7.6 Hz, 1H), 7.40 (d, J = 7.6 Hz, 2H),
7.18-7.12 (m, 2H), 7.03 (d, J = 6.8 Hz, 1H), 2.76 (t, J = 7.6 Hz, 2H), 1.97 (s, 3H),
1.69-1.62 (m, 2H), 1.35-1.28 (m, 2H), 0.84 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
CDCl3): δ = 191.9, 159.4, 158.1, 139.0, 136.9, 136.2, 135.0, 130.9, 129.5, 129.2,
126.4, 121.9, 121.1, 119.4, 118.8, 117.7, 32.9, 24.2, 22.7, 19.8, 13.9. IR (KBr, cm-1):
3051, 1689, 1558, 1419, 1273, 1029, 777, 706. HRMS (EI) m/z calcd for
17

ACCEPTED MANUSCRIPT
C24H23N3NaO+ [M+Na+] 392.1739, found 392.1721.
4.2.10. 2,3-Diphenyl-7-methoxy-1-(pyrimidin-2-yl)-1H-indole (3j). White solid, mp
190-191 °C. 1H NMR (400 MHz, CDCl3): δ = 8.64 (d, J = 4.8 Hz, 2H), 7.37-7.35 (m,
3H), 7.28-7.19 (m, 5H), 7.14-7.08 (m, 5H), 6.70 (d, J = 7.6 Hz, 1H), 3.60 (s, 3H). 13C
NMR (100 MHz, CDCl3): δ = 159.7, 157.7, 147.0, 137.7, 134.7, 131.5, 131.1, 130.3,
130.1, 128.3, 127.8, 127.6, 127.5, 126.1, 121.8, 119.5, 118.0, 112.8, 105.1, 56.0. IR
(KBr, cm-1): 1560, 1495, 1415, 1275, 1143, 1076, 705. HRMS (EI) m/z calcd for
C25H20N3O+ [M+H+] 378.1606, found 378.1590.
4.2.11. 2,3-Diethyl-7-methoxy-1-(pyrimidin-2-yl)-1H-indole (3k). Yellow oil. 1H
NMR (400 MHz, CDCl3): δ = 8.77 (d, J = 4.8 Hz, 2H), 7.22-7.16 (m, 2H), 7.06 (t, J
= 7.8 Hz, 1H), 6.63 (d, J = 7.6 Hz, 1H), 3.60 (s, 3H), 2.78-2.70 (m, 4H), 1.26 (t, J =
7.6 Hz, 3H), 0.98 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.3, 157.8,
147.0, 138.9, 131.2, 126.6, 120.9, 118.8, 116.2, 111.5, 104.3, 55.8, 18.1, 17.7, 15.7,
14.9. IR (film, cm-1): 2968, 1564, 1419, 1220, 1156, 1076, 754, 706. HRMS (EI) m/z
calcd for C17H19N3O+ [M+] 281.1528, found 281.1521.
4.2.12. 7-Methoxy-3-methyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3l). White solid,
mp 155-156 °C. 1H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 4.8 Hz, 2H), 7.29-7.04
13
(m, 8H), 6.68 (d, J = 7.6 Hz, 1H), 3.59 (s, 3H), 2.32 (s, 3H). C NMR (100 MHz,
CDCl3): δ = 159.8, 157.6, 147.0, 137.6, 132.1, 131.7, 130.4, 127.9, 127.4, 127.3,
121.2, 119.1, 112.1, 105.1, 55.9, 9.7. IR (KBr, cm-1): 2972, 1562, 1489, 1416, 1158,
1088, 854, 697. HRMS (EI) m/z calcd for C20H17N3NaO+ [M+Na+] 338.1269, found
338.1261.
18

ACCEPTED MANUSCRIPT
4.2.13. 3-Ethyl-7-methoxy-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3m). White solid,
mp 123-124 °C. 1H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 4.8 Hz, 2H), 7.31-7.20
(m, 6H), 7.11-7.03 (m, 2H), 6.68 (d, J = 8.0 Hz, 1H), 3.59 (s, 3H), 2.75 (q, J = 7.6 Hz,
2H), 1.27 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.6, 157.5, 147.1,
137.2, 132.2, 130.7, 130.4, 130.0, 127.9, 127.4, 121.1, 119.0, 118.6, 112.3, 104.9,
55.9, 18.0, 15.7. IR (KBr, cm-1): 2954, 1610, 1437, 1415, 1240, 1175, 1045, 840, 760,
699. HRMS (EI) m/z calcd for C21H20N3O+ [M+H+] 330.1606, found 330.1592.
4.2.14. 3-Butyl-7-methoxy-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3n). White solid,
mp 93-94 °C. 1H NMR (400 MHz, CDCl3): δ = 8.60 (d, J = 4.8 Hz, 2H), 7.30-7.18 (m,
6H), 7.11-7.05 (m, 2H), 6.68 (d, J = 8.0 Hz, 1H), 3.60 (s, 3H), 2.73 (t, J = 7.8 Hz,
13
2H), 1.70-1.61 (m, 2H), 1.36-1.28 (m, 2H), 0.84 (t, J = 7.2 Hz, 3H). C NMR (100
MHz, CDCl3): δ = 159.6, 157.5, 147.0, 137.5, 132.2, 131.0, 130.5, 127.8, 127.3,
127.2, 121.0, 118.9, 117.1, 112.4, 104.8, 55.8, 33.0, 24.4, 22.8, 13.9. IR (KBr, cm-1):
2953, 1609, 1568, 1376, 1181, 1161, 1097, 781, 697. HRMS (EI) m/z calcd for
C23H23N3NaO+ [M+Na+] 380.1739, found 380.1739.
4.2.15. 3-Butyl-7-methoxy-2-(4-methoxyphenyl)-1-(pyrimidin-2-yl)-1H-indole (3o).
1
White solid, mp 115-116 °C. H NMR (400 MHz, CDCl3): δ = 8.61 (d, J = 4.8 Hz,
2H), 7.27 (d, J = 8.0 Hz, 1H), 7.20 (d, J = 8.4 Hz, 2H), 7.11-7.06 (m, 2H), 6.77 (d, J
= 8.4 Hz, 2H), 6.66 (d, J = 8.0 Hz, 1H), 3.75 (s, 3H), 3.59 (s, 3H), 2.71 (t, J = 7.6 Hz,
13
2H), 1.69-1.60 (m, 2H), 1.36-1.29 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H). C NMR (100
MHz, CDCl3): δ = 159.7, 158.8, 157.5, 146.9, 137.4, 131.7, 131.0, 127.2, 124.4,
120.9, 118.9, 116.7, 113.3, 112.3, 104.7, 55.8, 55.1, 33.0, 24.4, 22.7, 13.9. IR (KBr,
19

ACCEPTED MANUSCRIPT
cm-1): 3047, 1562, 1417, 1245, 987, 706. HRMS (EI) m/z calcd for C24H25N3NaO2
[M+Na+] 410.1844, found 410.1845.
+
4.2.16. 2,3-Diphenyl-7-trifluoromethyl-1-(pyrimidin-2-yl)-1H-indole (3p). White solid,
mp 147-149 °C. 1H NMR (400 MHz, CDCl3): δ = 8.63 (d, J = 4.8 Hz, 2H), 7.93 (d, J
13
= 8.0 Hz, 1H), 7.60 (d, J = 7.6 Hz, 1H), 7.34-7.08 (m, 12H). C NMR (100 MHz,
CDCl3): δ = 159.2, 158.4, 139.7, 133.6, 132.7, 131.3, 130.9, 130.4, 128.4, 128.0,
127.8, 126.7, 124.4, 123.9, 122.5, 120.7, 120.3, 118.2, 114.6, 114.3. IR (KBr, cm-1):
1562, 1483, 1413, 1288, 1172, 1135, 1107, 1065, 705. HRMS (EI) m/z calcd for
+
C25H16F3N3 [M+] 415.1296, found 415.1287.
4.2.17. 5,7-Dimethyl-2,3-diphenyl-1-(pyrimidin-2-yl)-1H-indole (3q). White solid, mp
1
181-182 °C. H NMR (400 MHz, CDCl3): δ = 8.63 (d, J = 4.8 Hz, 2H), 7.39 (s, 1H),
7.35 (d, J = 7.2 Hz, 2H), 7.28 (t, J = 7.6 Hz, 2H), 7.22-7.06 (m, 7H), 6.86 (s, 1H),
2.39 (s, 3H), 1.92 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.8, 158.1, 138.1,
135.2, 134.9, 131.9, 131.1, 130.9, 130.4, 129.2, 128.2, 127.8, 127.7, 127.4, 126.1,
121.3, 119.6, 117.9, 117.5, 21.4, 19.4. IR (KBr, cm-1): 1557, 1416, 1272, 1197, 1145,
+
1073, 921, 776, 701. HRMS (EI) m/z calcd for C26H21N3 [M+] 375.1735, found
375.1740.
4.2.18. 2,3-Diethyl-5,7-dimethyl-1-(pyrimidin-2-yl)-1H-indole (3r). Light yellow oil.
1H NMR (400 MHz, CDCl3): δ = 8.80 (d, J = 4.8 Hz, 2H), 7.23-7.19 (m, 2H), 6.76 (s,
1H), 2.77-2.69 (m, 4H), 2.41 (s, 3H), 1.89 (s, 3H), 1.25 (t, J = 7.6 Hz, 3H), 0.95 (t, J
13
= 7.4 Hz, 3H). C NMR (100 MHz, CDCl3): δ = 159.4, 158.3, 139.2, 134.6, 130.2,
130.0, 126.3, 121.4, 118.7, 116.2, 116.1, 21.3, 19.9, 18.3, 17.6, 15.6, 14.9. IR (film,
20

ACCEPTED MANUSCRIPT
+
cm-1): 3064, 1565, 1421, 1197, 802, 706. HRMS (EI) m/z calcd for C18H21N3 [M+]
279.1735, found 279.1724.
4.2.19. 2-Phenyl-3,5,7-trimethyl-1-(pyrimidin-2-yl)-1H-indole (3s). White solid, mp
134-135 °C. 1H NMR (400 MHz, CDCl3): δ = 8.57 (d, J = 4.8 Hz, 2H), 7.27 (s, 1H),
7.23-7.17 (m, 5H), 7.03 (t, J = 4.8 Hz, 1H), 6.83 (s, 1H), 2.43 (s, 3H), 2.28 (s, 3H),
1.92 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 159.9, 158.0, 138.0, 135.1, 132.5,
130.7, 130.4, 130.2, 127.8, 127.4, 127.2, 121.3, 119.1, 116.8, 112.0, 21.4, 19.6, 9.5.
IR (KBr, cm-1): 3053, 1605, 1415, 1086, 1047, 861, 740. HRMS (EI) m/z calcd for
+
C21H19N3 [M+] 313.1579, found 313.1592.
4.2.20. 5,7-Dimethyl-3-ethyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3t). White solid,
1
mp 124-126 °C. H NMR (400 MHz, CDCl3): δ = 8.58 (d, J = 4.8 Hz, 2H), 7.32 (s,
1H), 7.23-7.18 (m, 5H), 7.03 (t, J = 4.8 Hz, 1H), 6.83 (s, 1H), 2.71 (q, J = 7.6 Hz,
2H), 2.44 (s, 3H), 1.92 (s, 3H), 1.25 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3):
δ = 159.7, 157.9, 137.6, 135.0, 132.6, 130.5, 130.1, 129.7, 127.8, 127.3, 121.4, 119.0,
118.5, 117.0, 21.4, 19.7, 17.9, 15.7. IR (KBr, cm-1): 2960, 1609, 1561, 1460, 1416,
+
1238, 1160, 854, 779, 760. HRMS (EI) m/z calcd for C22H22N3 [M+H+] 328.1814,
found 328.1794.
4.2.21. 3-Butyl-5,7-dimethyl-2-(4-methoxyphenyl)-1-(pyrimidin-2-yl)-1H-indole (3u).
1
White solid, mp 112-113 °C. H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 4.8 Hz,
2H), 7.29 (s, 1H), 7.14 (d, J = 8.8 Hz, 2H), 7.05 (t, J = 4.8 Hz, 1H), 6.81 (s, 1H), 6.76
(d, J = 8.8 Hz, 2H), 3.74 (s, 3H), 2.67 (t, J = 7.8 Hz, 2H), 2.43 (s, 3H), 1.90 (s, 3H),
1.66-1.60 (m, 2H), 1.33-1.29 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz,
21

ACCEPTED MANUSCRIPT
CDCl3): δ = 159.8, 158.8, 157.9, 137.9, 134.9, 131.8, 129.9, 127.0, 124.9, 121.2,
119.0, 116.9, 116.7, 113.2, 55.1, 33.0, 24.3, 22.8, 21.4, 19.6, 14.0. IR (KBr, cm-1):
2921, 1561, 1489, 1415, 1088, 1047, 853, 697. HRMS (EI) m/z calcd for C25H27N3O+
[M+] 385.2154, found 385.2147.
4.2.22. 3-Butyl-5,7-dimethyl-2-phenyl-1-(pyrimidin-2-yl)-1H-indole (3v). White solid,
1
mp 114-116 °C. H NMR (400 MHz, CDCl3): δ = 8.59 (d, J = 4.8 Hz, 2H), 7.30 (s,
1H), 7.23-7.20 (m, 5H), 7.06 (t, J = 4.8 Hz, 1H), 6.83 (s, 1H), 2.69 (t, J = 7.8 Hz, 2H),
2.44 (s, 3H), 1.92 (s, 3H), 1.66-1.61 (m, 2H), 1.33-1.28 (m, 2H), 0.84 (t, J = 7.4 Hz,
3H). 13C NMR (100 MHz, CDCl3): δ = 159.7, 157.9, 137.9, 134.9, 132.7, 130.5,
130.0, 129.9, 127.7, 127.2, 121.3, 118.9, 117.1, 117.0, 33.0, 24.3, 22.8, 21.4, 19.7,
13.9. IR (KBr, cm-1): 2926, 1561, 1415, 1373, 1175, 1159, 961, 725. HRMS (EI) m/z
+
calcd for C24H25N3 [M+] 355.2048, found 355.2038.
4.2.23. 2,3-Diphenyl-1-(pyrimidin-2-yl)-1H-benzo[g]indole (3w). White solid, mp
1
179-180 °C. H NMR (400 MHz, CDCl3): δ = 8.71 (d, J = 4.8 Hz, 2H), 7.89 (d, J =
8.0 Hz, 1H), 7.84 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.40 (d, J = 7.6 Hz,
2H), 7.33-7.07 (m, 11H), 6.81 (d, J = 8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ =
160.2, 159.0, 137.2, 134.5, 132.1, 131.6, 131.5, 131.3, 130.5, 129.3, 128.4, 127.9,
127.6, 126.4, 125.3, 125.1, 123.9, 123.0, 122.2, 120.8, 120.5, 119.5, 119.2. IR (KBr,
+
cm-1): 1556, 1417, 1269, 1193, 1068, 906, 702. HRMS (EI) m/z calcd for C28H20N3
[M+H+] 398.1657, found 398.1668.
4.2.24. 3-Methyl-2-phenyl-1-(pyrimidin-2-yl)-1H-benzo[g]indole (3x). White solid,
mp 197-198 °C. 1H NMR (400 MHz, CDCl3): δ = 8.72 (d, J = 4.8 Hz, 2H), 7.90 (d, J
22

ACCEPTED MANUSCRIPT
= 8.0 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 8.4 Hz, 1H), 7.33-7.13 (m, 8H),
6.93 (d, J = 8.4 Hz, 1H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 160.4, 158.9,
137.3, 132.2, 132.0, 130.6, 129.3, 127.9, 127.3, 126.5, 125.1, 123.5, 122.3, 122.2,
120.9, 120.1, 118.9, 113.1, 9.5. IR (KBr, cm-1): 3050, 1562, 1425, 1294, 1032, 804,
+
702. HRMS (EI) m/z calcd for C23H17N3 [M+] 335.1422, found 335.1412.
4.2.25. 3-Ethyl-2-phenyl-1-(pyrimidin-2-yl)-1H-benzo[g]indole (3y). White solid, mp
1
156-157 °C. H NMR (400 MHz, CDCl3): δ = 8.67 (d, J = 4.8 Hz, 2H), 7.89 (d, J =
8.0 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.32-7.21 (m, 6H),
7.16-7.11 (m, 2H), 6.88 (d, J = 8.4 Hz, 1H), 2.82 (q, J = 7.6 Hz, 2H), 1.30 (t, J = 7.4
13
Hz, 3H). C NMR (100 MHz, CDCl3): δ = 160.3, 158.8, 136.8, 132.2, 131.9, 131.3,
130.7, 129.3, 127.9, 127.4, 125.6, 125.0, 123.5, 122.3, 122.2, 120.9, 120.0, 119.6,
119.0, 17.9, 16.0. IR (KBr, cm-1): 2966, 1564, 1421, 1274, 1025, 808, 698. HRMS (EI)
m/z calcd for C24H19N3Na+ [M+Na+] 372.1477, found 372.1465.
4.2.26. 3-Butyl-2-phenyl-1-(pyrimidin-2-yl)-1H-benzo[g]indole (3z). White solid, mp
1
161-162 °C. H NMR (400 MHz, CDCl3): δ = 8.66 (d, J = 4.8 Hz, 2H), 7.89 (d, J =
8.0 Hz, 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.31-7.20 (m, 6H),
7.16-7.10 (m, 2H), 6.87 (d, J = 8.4 Hz, 1H), 2.81 (t, J = 7.8 Hz, 2H), 1.72-1.64 (m,
13
2H), 1.38-1.31 (m, 2H), 0.85 (t, J = 7.4 Hz, 3H). C NMR (100 MHz, CDCl3): δ =
160.3, 158.8, 137.2, 132.3, 131.9, 131.3, 130.8, 129.3, 127.9, 127.4, 125.9, 125.0,
123.5, 122.3, 122.2, 120.9, 120.0, 119.2, 118.1, 33.4, 24.2, 22.8, 14.0. IR (KBr, cm-1):
2959, 1561, 1491, 1415, 1239, 1045, 806, 759, 725. HRMS (EI) m/z calcd for
C26H23N3Na+ [M+Na+] 400.1790, found 400.1778.
23

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4.2.27. 2,3-Diphenyl-6-methyl-1-(pyrimidin-2-yl)-1H-indole (3a'). White solid, mp
1
151-153 °C. H NMR (400 MHz, CDCl3): δ = 8.55 (d, J = 4.8 Hz, 2H), 7.93 (s, 1H),
7.55 (d, J = 8.4 Hz, 1H), 7.33-7.05 (m, 11H), 6.95 (t, J = 4.8 Hz, 1H), 2.49 (s, 3H).
13C NMR (100 MHz, CDCl3): δ = 158.2, 137.5, 135.6, 134.5, 134.0, 133.1, 130.4,
130.3, 128.3, 127.9, 127.2, 127.0, 126.5, 123.9, 120.3, 119.5, 117.6, 112.6, 22.1. IR
(KBr, cm-1): 3064, 1566, 1421, 1241, 1116, 802, 706. HRMS (EI) m/z calcd for
+
C25H19N3 [M+] 361.1579, found 361.1565.
1
4.2.28. 6-Methyl-2,3-diethyl-1-(pyrimidin-2-yl)-1H-indole (3b'). Yellow oil. H NMR
(400 MHz, CDCl3): δ = 8.77 (d, J = 4.8 Hz, 2H), 8.02 (s, 1H), 7.41 (d, J = 8.0 Hz,
1H), 7.08 (t, J = 4.8 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 3.15 (q, J = 7.2 Hz, 2H), 2.75
(q, J = 7.6 Hz, 2H), 2.47 (s, 3H), 1.25 (t, J = 7.4 Hz, 3H), 1.07 (t, J = 7.4 Hz, 3H).
13C NMR (100 MHz, CDCl3): δ = 158.4, 158.1, 137.6, 136.8, 132.3, 127.5, 122.8,
118.7, 117.7, 116.6, 113.6, 22.0, 19.3, 17.5, 15.4, 15.1. IR (film, cm-1): 2965, 1560,
+
1489, 1418, 1339, 1268, 1207, 1053, 805. HRMS (EI) m/z calcd for C17H19N3 [M+]
265.1579, found 265.1583.
4.3. Synthesis of 7-methyl-2,3-diphenyl-1H-indole (4a).
A mixture of 7-methyl-2,3-diphenyl-1-(pyrimidin-2-yl)-1H-indole (3a) (180 mg,
0.50 mmol), NaOEt (102 mg, 1.50 mmol) and DMSO (2.0 mL) was stirred at 120 °C
under Ar for 24 h. After cooling to room temperature, the reaction mixture was diluted
with EtOAc (50 mL) and washed with brine (2 × 20 mL). The aqueous phase was
extracted with EtOAc (2 × 20 mL), and the combined organic phase was dried over
MgSO4. After removal of the solvents under reduced pressure, the crude product was
24

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purified by column chromatography on silica gel (light petroleum ether/EtOAc: 20/1)
to give 4a as a white solid.
1
4.3.1. 7-Methyl-2,3-diphenyl-1H-indole (4a). White solid, mp 141-142 °C. H NMR
(400 MHz, CDCl3): δ = 8.11 (br, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.45-7.23 (m, 10H),
7.10-7.02 (m, 2H), 2.53 (s, 3H). 13C NMR (100 MHz, CDCl3): δ = 135.6, 135.4, 134.0,
133.0, 130.3, 128.8, 128.6, 128.4, 127.7, 126.3, 123.4, 120.8, 120.2, 117.6, 115.7,
16.7. IR (KBr, cm-1): 1663, 1556, 1480, 1305, 1273, 1072, 743, 699. HRMS (EI) m/z
calcd for C21H17N+ [M+] 283.1361, found 283.1354.
Acknowledgements
We thank the National Natural Science Foundation of China (No. 21462021) and
Key Laboratory of Functional Small Organic Molecule, Ministry of Education (No.
KLFS-KF-201409) for financial support.
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