Iron(III) chloride as a mild catalyst for the dearomatizing cyclization of n-acylindoles

Article abstract of DOI:10.1021/acs.joc.0c01373

A catalytic approach for the preparation of indolines by dearomatizing cyclization is presented. FeCl3 acts as a catalyst to afford tetracyclic 5a,6-dihydro-12H-indolo[2,1-b][1,3]benzoxazin-12-ones in good yields. The cyclization also proceeds with tosylamides forming C-N bonds in 53% yield.

Full text of DOI:10.1021/acs.joc.0c01373

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Article
Iron(III) chloride as mild catalyst for the
dearomatizing cyclization of N-acylindoles
Jingyu Zhang, Jing Li, Jas S Ward, Khai-Nghi Truong, Kari Rissanen, and Markus Albrecht
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c01373 • Publication Date (Web): 28 Aug 2020
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Page 1 of 16
The Journal of Organic Chemistry
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Iron(III) chloride as mild catalyst for the dearomatizing cyclization
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of N-acylindoles
Jingyu Zhang,[a] Jing Li,[a] Jas S. Ward,[b] Khai-Nghi Truong,[b] Kari Rissanen[b] and Markus Albrecht*[a]
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[a] Institut für Organische Chemie, RWTH Aachen University, Landoltweg 1, Aachen 52074, Germany
[b] University of Jyvaskyla, Department of Chemistry, P.O. Box 35, FIN-40014 Jyväskylä, Finland
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Supporting Information Placeholder
R1
R1
R2
Nu
R2
FeCl3 (10 mol%), CHCl3 (1.0 mL)
H2O (60 mol%), air, 24 h
NuH
N
R3
R3
N
O
O
NuH=OH, NHTs




non noble metal catalyst
yields up to 89% yield
scalable
mild reaction conditions
ABSTRACT: A catalytic approach for the preparation of indolines by dearomatizing cyclization is presented. FeCl3 acts as a catalyst
to afford tetracyclic 5a,6-dihydro-12H-indolo[2,1-b][1,3]benzoxazin-12-ones in good yields. The cyclization also proceeds with
tosylamides forming C-N bonds in 53 % yield.
dearomatization cyclization have been shown (Scheme 1).7-8
■ INTRODUCTION
Respective dearomatizing cyclizations have been achieved
applying either a quinine organocatalyst in the presence of a
fluorine source, aluminium triflate or palladium catalysts. The
cyclizations hereby proceed by C-C or C-O bond formation.
Indole is a basic heterocyclic motif found in important natural
(e.g. alkaloids) or non-natural organic derivatives (e.g. dyes).
The parent molecule is rather old and its chemistry is well
explored. Functionalization at the heterocyclic part usually
proceeds in 3-position while 2-functionalization is possible
utilizing e.g. C-H activation approaches.1 Just recently
dearomatization reactions at the indole skeleton came into the
focus of attention.2-3 This is of special interest due to the
importance of indolines in natural products or as bioactives,4
Scheme 1. Cyclizing intramolecular dearomatization
reactions at the indole skeleton.
F
F
Ph
O
fluorine source
1,4-bis(dihydro-
quininyl)phthalazine
Ph
OH
N
N
e.g. in case of the Strychnos alkaloids (Figure 1).
50 %
NH
R2
O
R2
H
R3
COR
COR
O
R1
R2
R
R1
N
Al(OTf)3 (10 mol%)
<93 %
N
N
N
O
O
N
R1
H
O
O
O
O
R
R
tryptanthrins
(-)-physovenine
O
H
N
R
Br
R1
R2
Pd(0), L*, [H]
R2
<89 %
R1
N
N
N
H
N
N
O
H
O
O
R2
O
O
X
H
R1
R3
R1
R3
leuconocine
strychnine
[Pd]
R4
O
N
N
R4
<84 %
Figure 1. Indoline based natural products and bioactive
molecules.
O
O
HO
X
=O/CHR
BBr3 or TfOH
<96 %
O
HO
Consequently, the search for synthetic methodologies to make
indoline derivatives easily available has been in the focus of
attention for several decades. 5 The dearomatization reaction of
indoles is a facile approach to access indolines. Many methods
have been developed via intramolecular dearomatization and
intermolecular dearomatization.2,6 To date, some cases of the
use of N-substituted indoles to prepare indolines via
N
N
O
O
Just recently we introduced a protocol for the synthesis of tri-
and tetracyclic indolines from acyl-indoles using relatively
harsh reaction conditions by applying BBr3 or triflic acid to
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The Journal of Organic Chemistry
Page 2 of 16
c
d
facilitate the cyclization.8 However it is desired to develop
milder and more effective reaction conditions in order to obtain
the target molecules easily in high yields.
Isolated yield. 20 mol% H2O was added. 60 mol% H2O was
added. e 100 mol% H2O was added. f 140 mol% H2O was added.
1
2
3
4
5
6
7
8
9
In earlier studies Bronsted acids as well as BBr3 were used to
initiate the cyclization. However, with those reagents it was not
possible to perform the reaction in a catalytic fashion. 8 Initially
the reaction of acyl indole 1a to the indoline 2a was done using
one equivalent of different Lewis acids in dichloromethane at
room temperature for 24 hours. One equivalent of the
“classical” Lewis acid TiCl4 did not yield any product, while
B(OH)3, MnCl2·4H2O, CuCl2·2H2O, FeCl2·4H2O, AlCl3 as well
as Y(OTf)3 and Yb(OTf)3 afforded only small amounts of the
desired cyclization product. However, with Ga(OTf)3 the
product 2a was obtained in 90 % yield and with Fe(OTf)3,
FeCl3·6H2O in 73 %, 77 % yields, respectively.10 Finally, the use
of FeCl3 resulted in the quantitative formation of the indoline
2a (Table 1). Following this, FeCl3 was applied in catalytic
amounts (10 mol%) yielding 2a in 67 %. Switching of the
solvent to chloroform led to the product 2a in 73 % which could
be increased to 85 % at 60 °C. Addition of water (up to 140
mol%) did not significantly influence the reaction. The use of
only 1 mol% of catalyst reduced the yield of 2a to 10 %.
In recently published studies dearomatizing reactions at the
indole utilizing FeCl3 followed a radical mechanism.11 Addition
of 1 eq. 2,6-di-tert-butyl-4-methylphenol (BHT) as a radical
inhibitor during the cyclization of 1a with FeCl3 did not alter
the yields of the reaction (88 % of 2a). Moreover, another
proposed mechanism is also possible. The carbonyl group be
activated by FeCl3 and then protonation of the C3-position of
the indole activates the C2-position for nuclephilic attack. After
cyclization the FeCl3 dissociates from the carbonyl group and
the proton at oxygen dissociates. 12
The dearomatizing cyclization follows a proposed mechanism
as outlined in Scheme 2.9 The carbonyl group is activated by an
acid and then the addition of an acid to the 3-position of the
indole activates the 2-position for nucleophilic attack. After
cyclization the acid dissociates and the proton at oxygen
migrates to the 3-position.
Scheme 2. Proposed mechanism of the acid catalysed
dearomatising cyclization of hydroxybenzoylindole to the
corresponding indoline.
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acid
HO
HO
HO
acid
acid
N
N
N
+
O
O
O
acid
acid
acid
H
+
O
O
N
N
- acid
O
O
acid
■ RESULTS AND DISCUSSION
Table 1. Lewis acid catalysts for the dearomatizing
cyclization of acyl indole 1a to indoline 2a.a
Lewis acid (x equiv)
solvent (1.0 mL), T oC, air, 24 h
O
HO
N
N
1a
2a
O
O
Scheme 3. Scope of the dearomatizing cyclization of indoles
1 to indolines 2 catalysed by FeCl3.
Entry
1
Lewis acid (x eq)
TiCl4 (1.0)
Solvent T (oC)
2a/1a (%) b
0/98
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
DCM
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
rt
rt
R2
R2
HO
R1
R1
O
FeCl3 (10 mol %), CHCl3 (1.0 mL)
H2O (60 mol %), air, 60 oC, 24 h
2
B(OH)3 (1.0)
MnCl2·4H2O (1.0)
CuCl2·2H2O (1.0)
FeCl2·4H2O (1.0)
AlCl3 (1.0)
8/78
N
N
R3
R3
1
2
3
rt
13/81
23/76
20/74
31/66
90/9
O
O
4
rt
O
O
O
OH
O
N
5
rt
N
N
O
N
O
6
rt
O
O
Cl
CH3
a
2a
2b
2c
2d
89% (11%)
87% (13%);81%
68% (27%)
68%
7
Ga(OTf)3 (1.0)
Y(OTf)3 (1.0)
Yb(OTf)3 (1.0)
Fe(OTf)3 (1.0)
FeCl3·6H2O (1.0)
FeCl3 (1.0)
rt
R
8
rt
25/73
26/68
73/27
77/17
99/0
O
N
O
2f
2j
R=F; 0%
R=OH; 31% (32%)
N
O
*
2g
2h
2i
2k
2l
R=Cl; 69% (29%)
R=Br; 57% (39%)
R=CH3; 84%
R=NO2; 5%
9
rt
Cl
O
R=CN; 0%
10
11
12
13
14
15
16
17c
18d
19e
20f
21d
rt
2e
74% (22%)
Br
rt
O
N
O
H3C
N
O
O
N
rt
CH3
O
FeCl3 (0.1)
rt
67/28
73/22
79/17
85/14
86/14
87/13
85/13
86/14
10/87
O
2m
2n
2o
22% (57%)
26%
73% (11%)
FeCl3 (0.1)
rt
FeCl3 (0.1)
40
60
60
60
60
60
60
O
O
O
N
N
FeCl3 (0.1)
N
O
O
FeCl3 (0.1)
O
2p
2q
2r
68% (8%)
25%
88% (2%)
FeCl3 (0.1)
3
R
CH3
2
O
2t
2u
R=2-COOC2H5; 0%
R=3-CH3; 0%
O
FeCl3 (0.1)
N
O
N
O
2v R=3-CN; 0%
2w
FeCl3 (0.1)
R=3-COOCH3; 0%
2s
81%
FeCl3 (0.01)
Reaction conditions: 1 (0.5 mmol), FeCl3 (10 mol%), H2O (60
a
Unless otherwise noted, all reactions were performed on a 0.5
mmol scale, solvent (1.0 mL) in a sealed tube under air for 24 h. b
mol%) in CHCl3 (1.0 mL) at 60 oC (oil bath) under air for 24 h. The
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Page 3 of 16
The Journal of Organic Chemistry
yield of starting material recovery is given in brackets. a The yield
of gram reaction. * NMR yield.
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5
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7
8
9
To evaluate the applicability of this transformation, the
reaction was performed at 60 °C using 10 mol % FeCl3 with 60
mol % H2O in 1.0 mL of chloroform for 24 h of reaction time
(standard conditions). The scope of the reaction was shown in
Scheme 3. The cyclization reaction seems to be more or less
independent of the substituents at the N-benzoyl unit (2a-2e, 68-
89 % yield). Electron donating groups in 5- or 6-position of the
indole (2g-2j, 2n) do not affect the cyclization dramatically.
However, electron withdrawing groups in 5-position destabilize
a positive charge in 2-position and thus suppress the cyclization.
Only 5 % of product were obtained with a nitro group (2k)
while with fluorine or nitrile no target product 2f, 2l formation
has been observed. Obviously, the bromine in 4-position of
indole has a negative effect compared with the bromine in 5-
position of indole (2h, 2m). With the 7-methyl and the 6,7-
cycloalkane indole derivatives, only small amounts (22 %, 25
%) of 2o, 2p were obtained due to steric interaction of the
substitutents with the amide carbonyl oxygen. Substituents in
2-position of the indole heterocycle (2q-2s) result in good
cyclization yields (68-88 %) if the substituent does not
destabilize a positive charge (2t, no product observed).
Substituents in 3-position (2u-2w) suppress the attack of the
Lewis acid and thus do not result in product formation. 2u was
obtained earlier with TfOH, while BBr3 as sterically demanding
Lewis acid did not afford the cyclization product.8 In the light
of this observation, the formation of 2r seems to be a surprise.
Here the electronic activation of the 2-position seems to
override the steric blocking of the 3-position.
It was possible to crystallize representative compounds and to
perform X-ray structural analyses (Figure 2). As starting
material, the benzoyl indole 1i could be structurally
characterized. It is found that in the crystal the phenolic oxygen
shows a distance of only 2.96 Å to the 2-position of indole and
a dihedral angle N-C(O)-C-C(OH) of 53.3°. Only a slight
rotation around the Ccarbonyl-Cphenol bond has to occur to enable
cyclization resulting in a dihedral angle N-C(O)-C-C(O) of
18.4° with an O-C2 distance of 1.42 Å. In general, the obtained
tetracyclic systems 2 adopt a more or less wavy planar structure.
In the 2-substituted derivatives the phenyl (2q) or cyclohexyl
units (2r) stick out vertical to this plane.
2i
1i
2e
2d
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2n
2q
2r
Figure 2. Molecular structures of 1i, 2i 2e, 2d, 2n, 2q and 2r.
The corresponding intermolecular reaction between 1x and 4-
methyl phenol13 only proceeds with stoichiometric amounts of
FeCl3 and as described earlier14 results in 15 % yield of the C-
C coupling product 3 (Scheme 4, (a)). Cyclizations of the
pyrrole 1y, benzimidazole 1z or amine derivative 1zb do not
proceed. However, C-N bond formation can be accomplished
even with catalytic amounts of FeCl3 if the tosylated amine 1zc
is used for the reaction. The N-H coupled product 2zc was
characterized by X-ray diffraction. The reaction of 3-
hydroxybutyryl indole under standard conditions gave tricyclic
product 2za in 11 % yield.
(a)
HO
OH
FeCl3 (1 eq.)
CHCl3 (1.0 mL)
+
N
H2O (60 mol%)
air, 60 oC, 24 h
N
CH3
Ph
1x
Ph
3
15%
O
CH3
3
O
(b)
X
N
XH
N
Nu
FeCl3 (1 eq.), CHCl3 (1.0 mL)
H2O (60 mol%), air, 60 oC, 24 h
Nu
O
O
X=CH, N; Nu=OH, NH, NHR
N
N
O
HO
N
HO
N
CH3
O
1y
O
2za
O
1z
*
11%
R
N
N
O
2zc
2zb
2zc
, R=H, 0%
, R=Ts, 53%
Scheme 4. (a) Attempts to perform the FeCl3 catalyzed reaction
intermolecularly (3, 15 %, 1 eq. FeCl3). (b) Pyrrole (1y),
benzimidazole (1z) and amine (1zb) do not cyclize. C-N bond
formation proceeds, if the amine is tosylated (2zc). * NMR yield.
The structure of 3, 2zc in the crystal.
Some orientating reactions have been performed at the
tetracyclic 5a,6-dihydro-12H-indolo[2,1-b][1,3]benzoxazin-
12-one 2a. The skeleton is fairly stable in the presence of acid
or base. However, 2a can be aromatized by reaction with DDQ
(43 % of 3a) and it can be doubly brominated to obtain 2zd in
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Page 4 of 16
h. Then MeOH (1.0 mL) was added to quench the reaction. The
70 % yield. The latter could be characterized by X-ray
1
2
3
4
5
6
7
8
solution was added water (30 mL) and extracted with CH2Cl2 (20
mL) three times. The combined organic layer was dried with
Na2SO4. Then the solvent was evaporated under vacuum. The
residue was purified by flash chromatography on silica gel with n-
pentane/ethyl acetate as the solvent to afford the pure product.
diffraction showing the obtained substitution pattern (Scheme
5).
Scheme 5. Rearomatization and bromination of the indoline
2a.
O
General procedure 3 - the dearomatizing cyclization of (2-
hydroxyphenyl)(1H-indol-1-yl)methanones: A solution of the
(2-hydroxyphenyl)(1H-indol-1-yl)methanone (0.5 mmol), FeCl3
(8.2 mg, 10 mol %), H2O (5.4 µL, 60 mol%) in CHCl3 (1.0 mL)
was stirred in a sealed reaction tube under an atmosphere of air at
60 ℃ for 24 h. After being cooled to room temperature, the reaction
mixture was washed with water (10 mL) and extracted with CH2Cl2
(3×10 mL). The combined organic layer was dried with Na2SO4.
Then the solvent was evaporated under vacuum. The residue was
purified by flash chromatography on silica gel with n-pentane/ethyl
acetate as the solvent to afford the pure product.
N
2a
O
DDQ, Toluene
120 oC, 12 h
Br
2, AcOH
DCM, rt.
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10
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60
O
Br
Br
O
N
N
O
Br
O
Br
3a
2zd
70 %
43%
■ CONCLUSIONS
Gram-Scale Reaction: a solution of (2-Hydroxyphenyl)(1H-
indol-1-yl)methanone (1a, 1.0 g, 4.21 mmol), FeCl3 (68.1 mg, 0.42
mmol) and H2O (45.5 μL, 2.53 mmol ) in chloroform (8.5 mL) were
stirred in a flask under air at 60 °C for 24 h. The reaction mixture
was washed with water (30 mL) and extracted with CH2Cl2 (3×30
mL). The combined organic layer was dried with Na2SO4. Then the
solvent was evaporated under vacuum. The residue was purified by
flash chromatography on silica gel with n-pentane/ethylacetate =
40:1 as the solvent to afford the pure product 2a in a yield of 81%
(805 mg).
In conclusion in here a versatile reaction catalyzed by FeCl3 has
been studied which affords 5a,6-dihydro-12H-indolo[2,1-
b][1,3]benzoxazin-12-ones in a dearoamtizing cyclization at
indole in good yields. The reaction has a broad scope and
affords the hitherto rarely described 2-oxo substituted indoline
skeleton. As already indicated with example 2zc in the future
the method even can be expanded further and natural product
synthesis is envisaged.15
(1H-indol-1-yl)(2-methoxyphenyl)methanone (1A). 8 Purified by
silica gel column chromatography; White solid; Isolated yield: 483
mg, 96%; Rf (n-pentane/ethyl acetate = 30/1) = 0.13; mp 68-70 oC;
1H NMR (400 MHz, CDCl3): δ (ppm) 8.45 (d, J = 6.8 Hz, 1H), 7.57
(d, J = 7.8 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.45 (d, J = 7.2 Hz,
1H), 7.37 (t, J = 7.8 Hz, 1H), 7.31 (t, J = 7.4 Hz, 1H), 7.11-7.02 (m,
3H), 6.55 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (101
MHz, CDCl3): δ (ppm) 167.4, 156.5, 135.7, 132.3, 131.1, 129.2,
127.6, 125.0, 125.0, 124.0, 120.9, 120.9, 116.7, 111.6, 108.8, 55.8;
MS (EI+, 70 eV): m/z (%) = 252.0 (10), 251.0 (47) [M]+, 136.0 (9),
135.0 (100), 134.3 (2), 120.0 (1), 116.0 (4), 92.1 (7), 89.1 (4), 79.2
(2), 77.2 (12), 76.2 (1), 64.2 (2), 63.2 (3); IR (ATR) ν (cm−1) =
3330, 3151, 3123, 3006, 2976, 2934, 2837, 2496, 2326, 2162, 2085,
2047, 1951, 1911, 1789, 1745, 1672, 1598, 1538, 1487, 1454, 1430,
1382, 1345, 1291, 1244, 1205, 1148, 1113, 1069, 1016, 934, 890,
871, 747, 677. Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N,
5.57. Found: C, 76.44; H, 4.93; N, 5.59. HRMS (ESI) m/z :
[M+Na]+ calcd for C16H13NO2Na, 274.0839; found, 274.0836.
■ EXPERIMENTAL SECTION
General information. Chemicals and solvents were obtained from
commercial sources and used as received without further treatment.
Chemicals were purchased from Acros Organics, Alfa Aesar,
Sigma Aldrich, TCI. Air and moisture sensitive reactions were
carried out by using air free techniques under nitrogen. Analytical
thin-layer chromatography (TLC) was performed on Merck silica
gel 60, F254 precoated aluminium foil plates, visualized by UV
irradiation. Fluka silica gel (40-60 µm) was used for column
chromatography. Melting points were determined with a Büchi B-
540 melting-point apparatus. NMR spectra were measured with
VNMRS 400, VNMRS 600 instruments. EI mass spectra were
measured with a Finnigan SSQ 7000. HR-ESI mass spectra were
measured with a ThermoFisher Scientific LTQ Orbitrap XL of
samples in acidified methanol. FTIR spectra were measured with a
PerkinElmer Spectrum 100 via ATR. Elemental analysis was
performed by using Vario EL and Vario EL cube instruments from
Elementar.
(5-Chloro-2-methoxyphenyl)(1H-indol-1-yl)methanone
(1B).
Purified by silica gel column chromatography; Colorless solid;
Isolated yield: 1.194 g, 84%; Rf (n-pentane/ethyl acetate = 30/1) =
0.30; mp 89-92 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.43 (s,
1H), 7.57 (d, J = 7.8 Hz, 1H), 7.39-7.36 (m, 2H), 7.31 (t, J = 7.5
Hz, 1H), 7.09 (dd, J = 7.8, 1.8 Hz, 1H), 7.02 (d, J = 1.8 Hz, 2H),
6.56 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 166.3, 157.2, 138.0, 135.7, 131.1, 130.2, 127.2,
125.2, 124.2, 123.5, 121.2, 121.0, 116.6, 112.5, 109.1, 56.2; MS
(EI+, 70 eV): m/z (%) = 287.2 (12), 286.2 (7), 285.1 (45) [M]+,
256.2 (16), 254.3 (5), 251.2 (9), 250.2 (50), 231.2 (8), 228.1 (6),
225.2 (6), 195.2 (11), 182.2 (6), 171.1 (34), 170.1 (11), 169.1 (100),
140.2 (8), 135.2 (32), 126.2 (11), 125.2 (16), 116.2 (5), 111.2 (6),
105.2 (6), 97.3 (6), 91.2 (15), 85.2 (9), 83.2 (14), 77.3 (17), 51.4
(5); IR (ATR) ν (cm−1) = 3353, 3078, 3008, 2974, 2941, 2854,
2658, 2502, 2342, 2190, 2107, 2044, 2005, 1920, 1677, 1590, 1540,
1486, 1446, 1397, 1334, 1249, 1201, 1149, 1122, 1095, 1060, 1020,
Genernal procedure 1 - synthesis of N-acylindoles: Prepared
according to literature procedure.16a A solution of indole (5.0
mmol), tetrabutylammonium hydrogensulfate (30.6 mg, 0.09
mmol), powdered NaOH (600 mg, 15.0 mmol), 2-methoxybenzoyl
chloride (1.116 mL, 7.5 mmol), in CH2Cl2 (20 mL) were stirred in
a flask under air at room temperature for 5 h. The reaction mixture
was washed with water (30 mL) and extracted with CH2Cl2 (3×30
mL). The combined organic layer was dried with Na2SO4. Then the
solvent was evaporated under vacuum. The residue was purified by
flash chromatography on silica gel with n-pentane/ethyl acetate as
the solvent to afford the pure product.
Genernal procedure 2 - synthesis of (2-hydroxyphenyl)(1H-
indol-1-yl)methanones: Prepared according to literature
procedure.8 To a solution of N-acylindole (3.0 mmol) in CH2Cl2
(30 mL) under nitrogen was added BBr3 solution (1.0 M in CH2Cl2)
(3.6 mL, 3.6 mmol) at -78℃ and the reaction mixture was stirred 3
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The Journal of Organic Chemistry
938, 887, 822, 755, 717; Anal. Calcd for C16H12ClNO2: C, 67.26;
H, 4.23; N, 4.90. Found: C, 67.03; H, 4.17; N, 4.89.
129.3, 128.8, 125.1, 124.4, 121.0, 120.5, 117.6, 111.6, 108.0, 55.9;
1
2
3
4
5
6
7
8
MS (EI+, 70 eV): m/z (%) = 288.0 (3), 287.0 (12), 286.0 (8), 285.0
(39) [M]+, 150.0 (3), 136.1 (10), 135.1 (100), 120.0 (2), 92.1 (8),
77.2 (12), 64.2 (2), 63.2 (2); IR (ATR) ν (cm−1) = 3350, 3146, 3110,
3074, 3021, 2975, 2939, 2840, 2508, 2324, 2162, 2043, 2000, 1952,
1894, 1810, 1759, 1681, 1597, 1536, 1486, 1443, 1367, 1333, 1292,
1256, 1192, 1117, 1094, 1061, 1020, 943, 878, 816, 787, 755, 718;
Anal. Calcd for C16H12ClNO2: C, 67.26; H, 4.23; N, 4.90. Found:
C, 67.30; H, 4.33; N, 4.77.
(2,3-Dimethoxyphenyl)(1H-indol-1-yl)methanone (1C).8 Purified
by silica gel column chromatography; Brown oil; Isolated yield:
1
1.38 g, 98%; Rf (n-pentane/ethyl acetate =30/1) = 0.15; H NMR
(600 MHz, CDCl3): δ (ppm) 8.47 (br s, 1H), 7.57 (d, J = 7.8 Hz,
1H), 7.38 (t, J = 7.5 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 7.18 (t, J =
8.1 Hz, 1H), 7.09-7.07 (m, 2H), 7.01 (dd, J = 7.5, 1.2 Hz, 1H), 6.55
(d, J = 3.6 Hz, 1H), 3.93 (s, 3H), 3.84 (s, 3H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 166.9, 153.0, 146.3, 135.7, 131.2, 130.3,
127.6, 125.0, 124.6, 124.2, 121.0, 120.0, 116.7, 114.7, 108.9, 61.9,
56.1; MS (EI+, 70 eV): m/z (%) = 283.1 (2), 282.1 (12), 281.1 (54)
[M]+, 166.0 (13), 165.0 (100), 164.3 (3), 150.0 (4), 122.1 (11),
121.1 (5), 120.1 (2), 116.1 (4), 107.1 (5), 92.2 (3), 89.2 (4), 79.2
(2), 77.3 (5), 63.3 (2), 51.4 (2); IR (ATR) ν (cm−1) = 2939, 2836,
2163, 2017, 1917, 1691, 1583, 1536, 1475, 1448, 1378, 1336, 1266,
1235, 1202, 1082, 1047, 999, 930, 878, 828, 747, 669; Anal. Calcd
for C17H15NO3: C, 72.58; H, 5.37; N, 4.98. Found: C, 72.62; H,
5.23; N, 5.15.
(5-Bromo-1H-indol-1-yl)(2-methoxyphenyl)methanone
(1G).
9
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.634 g, 99%; Rf (n-pentane/ethyl acetate = 30/1) =
0.24; mp 90-91 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.33 (s,
1H), 7.70 (s, 1H), 7.52 (t, J = 7.8 Hz, 1H), 7.45 (t, J = 8.8 Hz, 2H),
7.10-7.07 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H), 6.48 (d, J = 4.8 Hz,
1H), 3.78 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm)
167.3, 156.5, 134.3, 132.8, 132.6, 129.3, 128.7, 127.8, 124.4,
123.6, 121.0, 118.0, 117.3, 111.6, 107.9, 55.9; MS (EI+, 70 eV):
m/z (%) = 330.9 (16), 330.0 (3), 329.0 (15) [M]+, 195.9 (2), 193.9
(2), 136.0 (9), 135.1 (100), 134.3 (2), 115.1 (5), 114.1 (2), 92.1 (8),
88.2 (2), 77.2 (14), 64.3 (2), 63.3 (2), 51.4 (2); IR (ATR) ν (cm−1)
= 3352, 3120, 3076, 3005, 2925, 2853, 2705, 2328, 2198, 2092,
2045, 1978, 1919, 1757, 1680, 1598, 1534, 1487, 1444, 1369, 1332,
1245, 1191, 1113, 1021, 942, 874, 753; Anal. Calcd for
C16H12BrNO2: C, 58.20; H, 3.66; N, 4.24. Found: C, 58.09; H, 3.48;
N, 4.25.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(1H-indol-1-yl)(2-methoxy-5-methylphenyl)methanone
(1D).
Purified by silica gel column chromatography; White solid;
Isolated yield: 947 mg, 89%; Rf (n-pentane/ethyl acetate = 20/1) =
0.38; mp 87-89 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.45 (s,
1H), 7.57 (d, J = 7.2 Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.31-7.29
(m, 2H), 7.25 (s, 1H), 7.08 (d, J = 3.0 Hz, 1H), 8.92 (d, J = 9.0 Hz,
1H), 6.54 (d, J = 3.6 Hz, 1H), 3.75 (s, 3H), 2.34 (s, 3H); 13C{1H}
NMR (151 MHz, CDCl3): δ (ppm) 167.6, 154.4, 135.7, 132.7,
131.1, 130.4, 129.6, 127.7, 125.0, 124.7, 124.0, 120.8, 116.7,
111.6, 108.7, 55.9, 20.5; MS (EI+, 70 eV): m/z (%) = 266.3 (15),
265.2 (100) [M]+, 264.1 (3), 246.2 (4), 150.3 (15), 149.2 (89), 134.2
(3), 130.2 (4), 116.2 (8), 106.2 (7), 105.2 (6), 91.3 (16), 89.2 (9),
78.3 (5), 77.3 (4), 66.1 (3), 64.4 (3); IR (ATR) ν (cm−1) = 3416,
3144, 3113, 3047, 3004, 2929, 2836, 2498, 2323, 2053, 1923, 1670,
1609, 1584, 1536, 1496, 1449, 1408, 1337, 1290, 1252, 1205, 1149,
1121, 1088, 1066, 1021, 934, 879, 816, 746, 680; Anal. Calcd for
C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C, 77.24; H, 5.49;
N, 5.04.
(2-Methoxyphenyl)(5-methyl-1H-indol-1-yl)methanone
(1H).
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.278 g, 96%; Rf (n-pentane/ethyl acetate = 10/1) =
0.30; mp 79-81 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.30 (s,
1H), 7.52-7.49 (m, 1H), 7.44-7.42 (m, 1H), 7.36 (s, 1H), 7.18 (d, J
= 8.4 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 7.02 (d, J = 8.4 Hz, 2H),
6.47 (d, J = 4.2 Hz, 1H), 3.78 (s, 3H), 2.46 (s, 3H); 13C{1H} NMR
(151 MHz, CDCl3): δ (ppm) 167.2, 156.5, 133.9, 133.6, 132.2,
131.4, 129.2, 127.6, 126.3, 125.0, 120.9, 120.8, 116.3, 111.6,
108.6, 55.8, 21.6; MS (EI+, 70 eV): m/z (%) = 267.0 (2), 266.1 (12),
265.1 (61) [M]+, 136.0 (10), 135.1 (100), 134.3 (2), 130.1 (5), 103.1
(2), 102.1 (2), 92.1 (7), 77.2 (14), 64.2 (2), 63.2 (2), 51.3 (2); IR
(ATR) ν (cm−1) = 3366, 3164, 3115, 3021, 2920, 2847, 2330, 2206,
2164, 2077, 1983, 1950, 1913, 1690, 1593, 1541, 1488, 1459, 1365,
1332, 1292, 1253, 1213, 1187, 1126, 1060, 1018, 941, 882, 814,
753, 661; Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N, 5.28.
Found: C, 76.78; H, 5.66; N, 5.19.
(4-Chloro-2-methoxyphenyl)(1H-indol-1-yl)methanone
(1E).
Purified by silica gel column chromatography; Light yellow solid;
Isolated yield: 1.28 g, 90%; Rf (n-pentane/ethyl acetate =30/1) =
0.45; mp 95-97 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.42 (s,
1H), 7.57 (d, J = 7.8 Hz, 1H), 7.38 (t, J = 8.4 Hz, 2H), 7.31 (t, J =
7.5 Hz, 1H), 7.09 (dd, J = 8.1, 1.5 Hz, 1H), 7.03 (d, J = 1.2 Hz, 2H),
6.56 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 166.3, 157.2, 138.0, 135.7, 131.1, 130.2, 127.2,
125.2, 124.2, 123.5, 121.2, 121.0, 116.6, 112.4, 109.1, 56.2; MS
(EI+, 70 eV): m/z (%) = 288.0 (3), 287.0 (14), 286.0 (9), 285.0 (43)
[M]+, 246.0 (3), 172.0 (3), 171.0 (37), 170.0 (10), 169.0 (100),
154.0 (2), 130.1 (5), 128.0 (3), 126.0 (10), 116.1 (6), 113.0 (3),
111.1 (7), 98.1 (2), 89.2 (5), 77.2 (3), 75.2 (3), 63.3 (5); IR (ATR)
ν (cm−1) = 3380, 3117, 3072, 2932, 2853, 2656, 2325, 2094, 1978,
1894, 1693, 1591, 1534, 1483, 1449, 1397, 1332, 1292, 1251, 1205,
1179, 1150, 1120, 1089, 1059, 1022, 950, 891, 816, 756, 718; Anal.
Calcd for C16H12ClNO2: C, 67.26; H, 4.23; N, 4.90. Found: C,
67.49; H, 3.92; N, 5.00.
(5-Methoxy-1H-indol-1-yl)(2-methoxyphenyl)methanone (1I).16b
Purified by silica gel column chromatography; Yellow solid;
Isolated yield: 476 mg, 85%; Rf (n-pentane/ethyl acetate = 8/1) =
0.30; mp 91-92 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.35 (s,
1H), 7.52-7.49 (m, 1H), 7.43 (dd, J = 7.5, 1.5 Hz, 1H), 7.08 (t, J =
7.5 Hz, 1H), 7.04-7.01 (m, 3H), 6.97 (dd, J = 9.0, 2.4 Hz, 1H), 6.48
(d, J = 3.6 Hz, 1H), 3.87 (s, 3H ), 3.79 (s, 3H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 167.0, 156.8, 156.5, 132.2, 132.1, 130.4,
129.2, 128.2, 124.9, 120.9, 117.4, 113.2, 111.6, 108.7, 103.8, 55.8;
MS (EI+, 70 eV): m/z (%) = 282.0 (8), 281.0 (40) [M]+, 145.9 (12),
136.0 (9), 134.9 (100), 131.0 (4), 117.0 (4), 102.9 (10), 92.0 (17),
77.0 (24), 76.0 (8), 64.0 (5), 63.0 (5), 51.1 (4); IR (ATR) ν (cm−1)
= 3321, 3151, 3122, 3045, 2983, 2944, 2827, 2658, 2491, 2323,
2220, 2173, 2107, 2051, 1992, 1945, 1911, 1855, 1794, 1665, 1598,
1538, 1467, 1380, 1340, 1287, 1243, 1189, 1110, 1064, 1021, 937,
882, 858, 799, 751, 721, 664; Anal. Calcd for C17H15NO3: C, 72.58;
H, 5.37; N, 4.98. Found: C, 72.70; H, 5.45; N, 5.09.
(5-Chloro-1H-indol-1-yl)(2-methoxyphenyl)methanone
(1F).
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.4 g, 99%; Rf (n-pentane/ethyl acetate = 10/1) =
o
1
0.30; mp 105-107 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.38
(br s, 1H), 7.54-7.51 (m, 2H), 7.44 (dd, J = 7.2, 1.8 Hz, 1H), 7.32
(dd, J = 8.7, 2.1 Hz, 1H), 7.10-7.08 (m, 2H), 7.03 (d, J = 9.0 Hz,
1H), 6.48 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 167.2, 156.5, 134.0, 132.6, 132.3, 129.5,
(2-Methoxyphenyl)(5-nitro-1H-indol-1-yl)methanone
(1J).16b
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.466 g, 99%; Rf (n-pentane/ethyl acetate = 10/1) =
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o
1
0.46; mp 153-155 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.54
(d, J = 9.0 Hz, 1H), 8.49 (s, 1H), 8.26 (d, J = 9.0 Hz, 1H), 7.57 (t,
J = 7.8 Hz, 1H), 7.49 (d, J = 7.2 Hz, 1H), 7.25 (d, J = 3.6 Hz, 1H),
7.12 (t, J = 7.2 Hz, 1H), 7.06 (d, J = 9.0 Hz, 1H), 6.69 (d, J = 3.6
Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm)
167.4, 156.6, 144.5, 138.7, 133.1, 131.0, 130.5, 129.5, 123.7,
121.2, 120.3, 117.1, 116.7, 111.7, 108.9, 55.9; MS (EI+, 70 eV):
m/z (%) = 297.1 (5), 296.1 (23) [M]+, 136.1 (8), 135.1 (100), 115.1
(2), 92.2 (7), 77.2 (10), 64.3 (2); IR (ATR) ν (cm−1) = 3123, 3006,
2925, 2847, 2503, 2204, 2158, 2038, 1979, 1908, 1775, 1688, 1601,
1513, 1442, 1381, 1320, 1249, 1195, 1137, 1070, 1042, 1016, 945,
915, 885, 828, 746, 709; Anal. Calcd for C16H12N2O4: C, 64.86; H,
4.08; N, 9.46. Found: C, 64.52; H, 3.94; N, 9.27.
for C17H15NO2: C, 76.96; H, 5.70; N, 5.28. Found: C, 76.86; H,
5.72; N, 5.25.
1
2
3
4
5
6
7
8
(2-Methoxyphenyl)(7-methyl-1H-indol-1-yl)methanone
(1N).
Purified by silica gel column chromatography; Purple oil; Isolated
yield: 1.258 g, 95%; Rf (n-pentane/ethyl acetate = 10/1) = 0.46; 1H
NMR (600 MHz, CDCl3): δ (ppm) 7.58 (dd, J = 7.5, 1.5 Hz, 1H),
7.55-7.52 (m, 1H), 7.42 (d, J = 7.2 Hz, 1H), 7.23 (t, J = 7.5 Hz,
1H), 7.18 (d, J = 7.8 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 7.04-7.03
(m, 2H), 6.52 (d, J = 3.6 Hz, 1H), 3.81 (s, 3H), 2.61 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 166.0, 157.8, 135.3,
133.2, 132.4, 130.9, 129.0, 127.9, 126.7, 124.6, 124.1, 120.8,
118.5, 111.9, 108.1, 56.0, 22.5; MS (EI+, 70 eV): m/z (%) = 267.0
(2), 266.1 (15), 265.1 (63) [M]+, 264.4 (2), 136.0 (14), 135.1 (100),
134.4 (2), 130.1 (5), 120.0 (2), 103.1 (2), 102.1 (2), 92.1 (8), 79.2
(2), 77.2 (16), 76.2 (2), 64.2 (2), 63.2 (2), 51.3 (2); IR (ATR) ν
(cm−1) = 3375, 3049, 2933, 2839, 2332, 2161, 2046, 1919, 1692,
1595, 1545, 1484, 1457, 1406, 1322, 1252, 1214, 1171, 1108, 1078,
1021, 947, 876, 785, 754, 722, 682; Anal. Calcd for C17H15NO2: C,
76.96; H, 5.70; N, 5.28. Found: C, 76.66; H, 5.85; N, 5.66.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1-(2-Methoxybenzoyl)-1H-indole-5-carbonitrile (1K). Purified by
silica gel column chromatography; White solid; Isolated yield:
1.307 g, 95%; Rf (n-pentane/ethyl acetate = 10/1) = 0.13; mp 143-
144 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.53 (d, J = 8.4 Hz,
1H), 7.90 (s, 1H), 8.7 (dd, J = 1.5 Hz, 1H), 7.57-7.54 (m, 1H), 7.46
(dd, J = 7.8, 1.8 Hz, 1H), 7.20 (d, J = 3.6 Hz, 1H), 7.11 (t, J = 7.5
Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.60 (d, J = 4.2 Hz, 1H), 3.78 (s,
3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 167.4, 156.5,
137.5, 133.0, 131.1, 129.7, 129.4, 128.2, 125.6, 123.9, 121.1,
119.8, 117.3, 111.7, 108.1, 107.3, 55.8; MS (EI+, 70 eV): m/z (%)
= 277.1 (6), 276.1 (32) [M]+, 141.1 (3), 136.1 (8), 135.1 (100),
134.3 (1), 120.1 (1), 114.1 (4), 92.1 (8), 79.2 (1), 77.2 (11), 64.2
(3), 63.2 (2), 51.3 (1); IR (ATR) ν (cm−1) = 3355, 3207, 3124, 3012,
2952, 2842, 2501, 2325, 2225, 2040, 1996, 1952, 1915, 1810, 1766,
1683, 1600, 1539, 1460, 1432, 1367, 1330, 1247, 1212, 1187, 1110,
1067, 1040, 1011, 944, 882, 816, 752, 661; Anal. Calcd for
C17H12N2O2: C, 73.90; H, 4.38; N, 10.14. Found: C,74.01; H, 4.43;
N, 9.86.
(7,8-Dihydrocyclopenta[g]indol-1(6H)-yl)(2-
methoxphenyl)methanone (1O). Purified by silica gel column
chromatography; White solid; Isolated yield: 1.237 g, 85%; Rf (n-
pentane/ethyl acetate = 40/1) = 0.20; mp 120-121 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 7.52-7.49 (m, 2H), 7.34 (d, J = 7.8 Hz, 1H),
7.22 (d, J = 7.8 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 7.02 (d, J = 8.4
Hz, 1H), 6.93 (d, J = 3.6 Hz, 1H), 6.49 (d, J = 3.6 Hz, 1H), 3.80 (s,
3H ), 3.47 (t, J = 7.2 Hz, 2H), 3.05 (t, J = 7.5 Hz, 2H), 2.14-2.09
(m, 2H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 166.2, 157.2,
142.9, 132.9, 132.7, 131.1, 130.5, 130.2, 127.8, 125.0, 120.9,
120.8, 118.7, 111.7, 108.6, 55.9, 35.2, 33.7, 25.7; MS (EI+, 70 eV):
m/z (%) = 292.1 (3), 291.0 (16) [M]+, 156.0 (6), 154.9 (6), 153.9
(18), 136.0 (9), 134.9 (100), 129.0 (6), 127.9 (9), 126.9 (7), 91.9
(19), 77.0 (37), 76.0 (4), 64.0 (6), 63.0 (5), 51.1 (6); IR (ATR) ν
(cm−1) = 3360, 3106, 3068, 3007, 2944, 2842, 2287, 2031, 1857,
1753, 1683, 1599, 1541, 1490, 1464, 1436, 1410, 1335, 1247, 1215,
1186, 1108, 1073, 1018, 949, 872, 804, 752, 722, 669; Anal. Calcd
for C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 78.09; H,
5.78; N, 4.78.
(4-Bromo-1H-indol-1-yl)(2-methoxyphenyl)methanone
(1L).
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.529 g, 93%; Rf (n-pentane/ethyl acetate = 35/1) =
o
1
0.15; mp 129-130 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.42
(d, J = 7.2 Hz, 1H), 7.54-7.52 (m, 1H), 7.47-7.44 (m, 2H), 7.24 (d,
J = 8.1 Hz, 1H), 7.12-7.09 (m, 2H), 7.03 (d, J = 8.4 Hz, 1H), 6.62
(d, J = 3.6 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 167.5, 156.5, 136.0, 132.6, 131.7, 129.3, 128.2,
126.9, 126.1, 124.4, 121.0, 115.7, 114.6, 111.6, 108.4, 55.8; MS
(EI+, 70 eV): m/z (%) = 330.9 (12), 328.9 (13) [M]+, 195.8 (5),
193.8 (5), 135.9 (9), 134.9 (100), 114.9 (13), 113.9 (5), 91.9 (18),
87.9 (5), 77.0 (29), 64.0 (7), 63.0 (7), 62.0 (5), 51.0 (5); IR (ATR)
ν (cm−1) = 3380, 3148, 3113, 3059, 3014, 2926, 2838, 2515, 2325,
2074, 1986, 1901, 1837, 1747, 1682, 1597, 1533, 1489, 1463, 1415,
1375, 1332, 1258, 1171, 1119, 1062, 1021, 947, 883, 817, 747, 675;
Anal. Calcd for C16H12BrNO2: C, 58.20; H, 3.66; N, 4.24. Found:
C, 58.27; H, 3.65; N, 4.23.
(2-Methoxyphenyl)(2-phenyl-1H-indol-1-yl)methanone (1P).7a
Purified by silica gel column chromatography; Green solid;
Isolated yield: 994 mg, 76%; Rf (n-pentane/ethyl acetate = 40/1) =
o
1
0.11; mp 130-132 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.11
(d, J = 7.8 Hz, 1H), 7.60 (d, J = 6.6 Hz, 1H), 7.34-7.28 (m, 2H),
7.26 (dd, J = 7.5, 1.5 Hz, 1H), 7.24-7.23 (m, 2H), 7.19-7.16 (m,
1H), 7.12-7.07 (m, 3H), 6.78 (t, J = 7.5 Hz, 1H), 6.63 (s, 1H), 6.53
(d, J = 8.4 Hz, 1H), 3.64 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 168.4, 157.1, 141.3, 138.0, 133.2, 133.1, 130.8,
129.5, 128.8, 127.6, 127.5, 125.9, 124.7, 123.5, 120.5, 120.2,
115.2, 110.9, 110.3, 55.4; MS (EI+, 70 eV): m/z (%) = 327.9 (7),
326.8 (35) [M]+, 191.9 (13), 190.9 (10), 189.9 (12), 165.9 (5), 164.9
(32), 163.9 (7), 162.9 (6), 136.0 (8), 134.9 (100), 92.1 (21), 77.1
(29), 64.2 (6), 63.2 (7); IR (ATR) ν (cm−1) = 3338, 3054, 2934,
2838, 2658, 2503, 2323, 2104, 1992, 1901, 1806, 1673, 1592, 1446,
1313, 1255, 1148, 1072, 1020, 920, 882, 829, 745, 699; Anal. Calcd
for C22H17NO2: C, 80.71; H, 5.23; N, 4.28. Found: C, 80.69; H,
5.26; N, 4.25.
(2-Methoxyphenyl)(6-methyl-1H-indol-1-yl)methanone
(1M).
Purified by silica gel column chromatography; Light brown solid;
Isolated yield: 1.312 g, 99%; Rf (n-pentane/ethyl acetate = 20/1) =
0.21; mp 85-88 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.35 (s,
1H), 7.52-7.49 (m, 1H), 7.45-7.43 (m, 2H), 7.14 (d, J = 7.8 Hz,
1H), 7.10-7.07 (m, 1H), 7.02 (d, J = 8.4 Hz, 1H), 6.96 (d, J = 3.6
Hz, 1H), 6.49 (d, J = 3.6 Hz, 1H), 3.79 (s, 3H), 2.52 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 167.4, 156.5, 136.1,
135.1, 132.1, 129.1, 128.8, 127.0, 125.4, 125.1, 120.9, 120.4,
117.0, 111.6, 108.7, 55.8, 22.1; MS (EI+, 70 eV): m/z (%) = 266.3
(19), 265.2 (89) [M]+, 144.1 (5), 136.2 (13), 135.1 (100), 134.0 (2),
130.1 (13), 128.0 (3), 120.1 (3), 103.2 (5), 102.0 (6), 92.1 (15), 79.2
(2), 78.3 (3), 77.1 (29), 64.2 (3), 63.1 (4); IR (ATR) ν (cm−1) =
3355, 3150, 3109, 3018, 2919, 2855, 2725, 2326, 2076, 1873, 1741,
1677, 1598, 1534, 1487, 1460, 1428, 1379, 1340, 1295, 1255, 1202,
1164, 1119, 1061, 1043, 1018, 937, 879, 803, 746, 665; Anal. Calcd
(2-Methoxyphenyl)(1,2,3,4-tetrahydro-9H-carbazol-9-
yl)methanone (1Q).7a Purified by silica gel column
chromatography; Colorless solid; Isolated yield: 1.48 g, 97%; Rf (n-
pentane/ethyl acetate =30/1) = 0.24; mp 118-120 oC; 1H NMR (400
MHz, CDCl3): δ (ppm) 7.50 (t, J = 7.0 Hz, 2H), 7.38 (t, J = 7.2 Hz,
2H), 7.20 (t, J = 7.4 Hz, 1H), 7.12 (t, J = 7.6 Hz, 1H), 7.06 (t, J =
7.6 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 3.75 (s, 3H), 2.66 (t, J = 5.6
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The Journal of Organic Chemistry
Hz, 2H), 2.49 (m, 2H), 1.81-1.75 (m, 4H); 13C{1H} NMR (101
1-(2-Methoxybenzoyl)-1H-indole-3-carbonitrile (1U). Purified by
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2
3
4
5
6
7
8
MHz, CDCl3): δ (ppm) 167.4, 156.9, 136.5, 135.9, 132.3, 130.5,
129.1, 127.0, 123.8, 123.1, 121.0, 118.3, 117.6, 115.3, 111.8, 55.9,
25.4, 23.8, 22.2, 21.3; MS (EI+, 70 eV): m/z (%) = 306.2 (11), 305.1
(48) [M]+, 170.1 (4), 169.1 (1), 168.1 (4), 167.1 (2), 140.1 (1),
136.1 (9), 135.1 (100), 134.4 (1), 120.1 (1), 115.1 (3), 92.2 (6), 79.3
(1), 77.2 (10), 76.3 (1); IR (ATR) ν (cm−1) = 3314, 3065, 2949,
2843, 2656, 2322, 2033, 1914, 1660, 1600, 1490, 1454, 1362, 1325,
1243, 1211, 1161, 1118, 1068, 1016, 930, 871, 832, 800, 751, 666;
Anal. Calcd for C20H19NO2: C, 78.66; H, 6.27; N, 4.59. Found: C,
78.33; H, 6.16; N, 4.56.
silica gel column chromatography; Light yellow solid; Isolated
yield: 1.354 g, 98%; Rf (n-pentane/ethyl acetate = 10/1) = 0.20; mp
141-144 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.46 (d, J = 8.4
Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.61-7.58 (m, 2H), 7.52-7.44 (m,
3H), 7.14 (t, J = 7.2 Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 3.80 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 166.9, 156.5, 135.1,
134.8, 133.6, 129.8, 128.4, 127.0, 125.4, 122.9, 121.4, 119.8,
117.0, 114.2, 111.8, 93.6, 56.0; MS (EI+, 70 eV): m/z (%) = 277.1
(4), 276.1 (22) [M]+, 141.1 (3), 136.1 (8), 135.1 (100), 120.2 (1),
114.2 (3), 105.2 (1), 92.2 (7), 79.3 (1), 77.3 (10), 64.4 (2), 63.3 (2),
51.4 (1); IR (ATR) ν (cm−1) = 3376, 3147, 3072, 3002, 2945, 2841,
2494, 2224, 2118, 2039, 1982, 1926, 1808, 1746, 1693, 1600, 1546,
1491, 1448, 1332, 1294, 1249, 1216, 1152, 1123, 1055, 1020, 946,
873, 749, 709, 659; Anal. Calcd for C17H12N2O2: C, 73.90; H, 4.38;
N, 10.14. Found: C, 72.54; H, 4.31; N, 9.58. HRMS (ESI) m/z :
[M+Na]+ calcd for C17H12N2O2Na, 299.0791; found, 299.0790.
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(2-Methoxyphenyl)(2-methyl-1H-indol-1-yl)methanone (1R).7a
Purified by silica gel column chromatography; Yellow solid;
Isolated yield: 1.19 g, 90%; Rf (n-pentane/ethyl acetate = 30/1) =
0.23; mp 81-84 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 7.52 (t,
J = 8.7 Hz, 1H), 7.44-7.41 (m, 2H), 7.35 (d, J = 8.4 Hz, 1H), 7.16
(t, J = 7.5 Hz, 1H), 7.09-7.05 (m, 2H), 6.99 (d, J = 8.4 Hz, 1H),
6.36 (s, 1H), 3.70 (s, 3H), 2.28 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 168.0, 157.1, 137.8, 137.1, 132.8, 129.9, 129.5,
126.5, 123.3, 123.1, 121.1, 119.6, 114.9, 111.8, 109.4, 55.9, 16.3;
MS (EI+, 70 eV): m/z (%) = 266.1 (10), 265.1 (49) [M]+, 264.3 (2),
137.0 (1), 136.0 (10), 135.1 (100), 134.4 (3), 130.1 (4), 128.0 (1),
120.0 (1), 103.1 (3), 102.1 (1), 92.1 (7), 89.1 (1), 79.2 (2), 78.2 (1),
77.2 (14), 76.2 (1), 64.2 (2), 63.2 (2), 51.3 (2); IR (ATR) ν (cm−1)
= 3019, 2972, 2937, 2836, 2209, 2160, 2018, 1959, 1918, 1670,
1595, 1490, 1445, 1359, 1331, 1301, 1252, 1204, 1159, 1111, 1018,
973, 942, 884, 838, 800, 754; Anal. Calcd for C17H15NO2: C, 76.96;
H, 5.70; N, 5.28. Found: C, 76.58; H, 5.71; N, 5.25.
Methyl 1-(2-methoxybenzoyl)-1H-indole-3-carboxylate (1V).
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.514 g, 98%; Rf (n-pentane/ethyl acetate =30/1) =
o
1
0.31; mp 148-149 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.48
(d, J = 7.8 Hz, 1H), 8.16 (dd, J = 6.6, 1.8 Hz, 1H), 7.76 (s, 1H),
7.58-7.55 (m, 1H), 7.47 (dd, J = 7.5, 1.5 Hz, 1H), 7.45-7.40 (m,
2H), 7.12 (t, J = 7.8 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 3.90 (s, 3H),
3.79 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 167.6,
164.7, 156.6, 136.1, 133.8, 133.1, 129.6, 127.9, 125.9, 125.1,
123.7, 121.7, 121.2, 116.6, 113.6, 111.8, 55.9, 51.7; MS (EI+, 70
eV): m/z (%) = 310.1 (8), 309.0 (34) [M]+, 278.0 (2), 146.1 (3),
143.1 (2), 137.0 (1), 136.0 (10), 135.1 (100), 134.4 (2), 120.0 (2),
115.1 (3), 114.1 (1), 103.1 (1), 92.2 (8), 88.2 (1), 79.3 (2), 78.3 (1),
77.2 (14), 76.3 (2), 64.3 (2), 63.3 (2), 51.4 (2); IR (ATR) ν (cm−1)
= 3152, 2951, 2846, 2343, 2038, 1904, 1791, 1712, 1677, 1600,
1565, 1445, 1376, 1329, 1279, 1254, 1191, 1144, 1049, 1016, 951,
873, 742, 706, 656; Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89;
N, 4.53. Found: C, 69.94; H, 4.85; N, 4.46.
Ethyl
1-(2-methoxybenzoyl)-1H-indole-2-carboxylate
(1S).
Purified by silica gel column chromatography; Colorless oil;
Isolated yield: 1.183 g, 73%; Rf (n-pentane/ethyl acetate = 20/1) =
1
0.16; H NMR (600 MHz, CDCl3): δ (ppm) 8.01 (d, J = 8.4 Hz,
1H), 7.65 (d, J = 7.8 Hz, 1H), 7.49-7.40 (m, 3H), 7.30 (t, J = 7.5
Hz, 1H), 7.23 (s, 1H), 7.00 (t, J = 7.5 Hz, 1H), 6.94 (d, J = 8.4 Hz,
1H), 3.90 (q, J = 7.2 Hz, 2H), 3.73 (s, 3H), 1.12 (t, J = 7.2 Hz, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 167.4, 161.4, 158.0,
138.6, 133.7, 131.7, 131.1, 127.6, 127.4, 125.4, 123.8, 122.3,
120.6, 115.8, 115.0, 111.8, 61.3, 55.9, 14.1; MS (EI+, 70 eV): m/z
(%) = 324.1 (8), 323.1 (38) [M]+, 278.0 (3), 144.0 (2), 143.0 (1),
137.0 (1), 136.0 (11), 135.0 (100), 134.3 (2), 120.0 (1), 116.1 (2),
115.1 (2), 114.1 (1), 105.0 (1), 92.2 (8), 92.1 (8), 89.1 (3), 79.2 (2),
77.1 (14), 64.2 (2), 63.2 (1); IR (ATR) ν (cm−1) = 3071, 2978, 2840,
2167, 2040, 1919, 1714, 1599, 1545, 1486, 1443, 1372, 1314, 1254,
1153, 1116, 1089, 1018, 960, 912, 884, 863, 749; Anal. Calcd for
C19H17NO4: C, 70.58; H, 5.30; N, 4.33. Found: C, 70.47; H, 5.11;
N, 5.15. HRMS (ESI) m/z : [M+Na]+ calcd for C19H17NO4Na,
346.1050; found, 346.1047.
(2-Methoxyphenyl)(1H-pyrrol-1-yl)methanone (1W).16c Purified
by silica gel column chromatography; Yellow oil; Isolated yield:
1.990 g, 99%; Rf (n-pentane/ethyl acetate =30/1) = 0.31; 1H NMR
(600 MHz, CDCl3): δ (ppm) 7.51-7.48 (m, 1H), 7.39 (dd, J = 7.5,
1.5 Hz, 1H), 7.16 (br s, 2H), 7.06-7.03 (m, 1H), 7.01 (d, J = 8.4 Hz,
1H), 6.28 (t, J = 2.1 Hz, 2H), 3.81 (s, 3H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 166.5, 156.9, 132.4, 129.3, 123.7, 120.7,
120.6, 113.2, 111.6, 55.9; MS (EI+, 70 eV): m/z (%) = 202.1 (4),
201.0 (28) [M]+, 182.3 (1), 165.1 (2), 155.1 (5), 148.2 (3), 136.1
(8), 135.1 (100), 134.3 (3), 132.2 (6), 120.1 (2), 118.2 (2), 105.2
(2), 92.2 (12), 91.2 (14), 79.3 (2), 78.3 (2), 77.3 (18), 76.3 (2), 66.4
(2), 65.4 (3), 64.4 (4), 63.4 (4), 51.5 (3), 50.5 (2); IR (ATR) ν (cm−1)
= 3385, 3146, 3008, 2942, 2840, 2332, 2159, 2039, 1921, 1700,
1599, 1463, 1400, 1330, 1250, 1166, 1117, 1077, 1044, 1020, 975,
879, 741, 663; Anal. Calcd for C12H11NO2: C, 71.63; H, 5.51; N,
6.96. Found: C, 70.19; H, 5.24; N, 7.75. HRMS (ESI) m/z :
[M+Na]+ calcd for C12H11NO2Na, 224.0682; found, 224.0681.
(2-Methoxyphenyl)(3-methyl-1H-indol-1-yl)methanone
(1T).8
Purified by silica gel column chromatography; White solid;
Isolated yield: 1.277 g, 96%; Rf (n-pentane/ethyl acetate = 30/1) =
o
1
0.23; mp 112-114 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.43
(s, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.41 (d, J = 7.2 Hz, 1H), 7.38 (t, J
= 7.5 Hz, 1H), 7.33 (t, J = 7.2 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H),
7.03 (d, J = 8.4 Hz, 1H), 6,83 (s, 1H), 3.80 (s, 3H), 2.22 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 166.9, 156.4, 136.0,
132.2, 132.0, 128.9, 125.3, 125.1, 124.2, 123.8, 120.8, 118.9,
118.0, 116.7, 111.6, 55.9, 9.9; MS (EI+, 70 eV): m/z (%) = 266.0
(10), 265.1 (45) [M]+, 264.4 (2), 136.0 (9), 135.0 (100), 134.2 (2),
130.1 (4), 120.0 (1), 103.1 (2), 92.1 (7), 79.2 (1), 78.2 (1), 77.2
(13), 76.2 (2), 64.2 (2), 63.2 (2), 51.3 (2); IR (ATR) ν (cm−1) =
3352, 3051, 2933, 2834, 2324, 2044, 1915, 1793, 1683, 1599, 1490,
1452, 1369, 1344, 1297, 1249, 1214, 1172, 1114, 1044, 1021, 939,
876, 748, 660; Anal. Calcd for C17H15NO2: C, 76.96; H, 5.70; N,
5.28. Found: C, 76.93; H, 5.77; N, 5.28.
(1H-benzo[d]imidazol-1-yl)(2-methoxyphenyl)methanone(1X).16d
Purified by silica gel column chromatography; White oil; Isolated
1
yield: 1.001 g, 79%; Rf (n-pentane/ethyl acetate =4/1) = 0.15; H
NMR (600 MHz, CDCl3): δ (ppm) 8.26 (d, J = 8.4Hz, 1H), 7.97 (s,
1H), 7.81-7.80 (m, 1H), 7.61-7.58 (m, 1H), 7.54 (dd, J = 7.5, 1.5
Hz, 1H), 7.46-7.40 (m, 2H), 7.14 (t, J = 7.8 Hz, 1H), 7.07 (d, J =
8.4 Hz, 1H), 3.79 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ
(ppm) 166.0, 156.7, 144.3, 143.8, 133.7, 131.8, 130.1, 125.9, 125.3,
123.1, 121.3, 120.5, 115.7, 111.8, 55.9; MS (EI+, 70 eV): m/z (%)
= 253.3 (8), 252.3 (41) [M]+, 136.2 (7), 135.2 (100), 120.1 (3), 92.1
(18), 90.1 (7), 79.2 (3), 77.2 (29), 76.1 (3), 64.2 (9), 63.1 (8), 51.1
(4), 50.1 (3); IR (ATR) ν (cm−1) = 3414, 3077, 2943, 2841, 2169,
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Page 8 of 16
2045, 1919, 1702, 1600, 1506, 1447, 1359, 1286, 1250, 1196, 1148,
8.4 Hz, 1H), 6.69 (d, J = 3.6 Hz, 1H), 2.32 (s, 3H); 13C{1H} NMR
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7
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1111, 1085, 1016, 941, 903, 875, 749, 680; Anal. Calcd for
C15H12N2O2: C, 71.42; H, 4.79; N, 11.10. Found: C, 70.53; H, 4.87;
N, 10.81. HRMS (ESI) m/z : [M+H]+ calcd for C15H13N2O2,
253.0972; found, 253.0971.
(151 MHz, CDCl3): δ (ppm) 170.8, 159.3, 136.3, 136.1, 131.1,
130.8, 128.6, 128.0, 125.0, 124.2, 121.2, 118.4, 116.2, 115.9,
109.0, 20.7; MS (EI+, 70 eV): m/z (%) = 252.2 (11), 251.1 (73)
[M]+, 136.2 (3), 118.2 (8), 117.2 (100), 116.3 (8), 107.2 (6), 106.3
(3), 105.2 (3), 90.3 (7), 89.3 (11), 79.3 (4), 78.3 (5), 77.3 (17), 64.4
(5), 56.5 (4), 55.0 (4), 45.4 (4); IR (ATR) ν (cm−1) = 3855, 3241,
2915, 2867, 2715, 2565, 2481, 2323, 2099, 1923, 1774, 1652, 1604,
1538, 1507, 1444, 1344, 1257, 1201, 1119, 1061, 1008, 929, 885,
820, 737, 681; Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N,
5.57. Found: C, 76.45; H, 5.16; N, 5.71.
(2-Hydroxyphenyl)(1H-indol-1-yl)methanone (1a).8 Purified by
silica gel column chromatography; White solid; Isolated yield:
1.225 g, 89%; Rf (n-pentane/ethyl acetate = 30/1) = 0.21; mp 108-
110 oC; 1H NMR (400 MHz, CDCl3): δ (ppm) 9.97 (s, 1H), 8.28 (d,
J = 8.0 Hz, 1H), 7.64-7.60 (m, 2H), 7.53 (t, J = 7.8 Hz, 1H), 7.47
(d, J = 3.6 Hz, 1H), 7.40 (t, J = 7.6 Hz, 1H), 7.33 (t, J = 7.6 Hz,
1H), 7.13 (d, J = 8.4 Hz, 1H), 6.99 (t, J = 7.4 Hz, 1H), 6.69 (d, J =
3.6 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ (ppm) 170.7,
161.5, 136.1, 135.4, 131.3, 130.8, 127.9, 125.1, 124.3, 121.2,
119.3, 118.6, 116.2, 116.1, 109.2; MS (EI+, 70 eV): m/z (%) =
238.0 (5), 237.0 (31) [M]+, 236.1 (1), 135.1 (2), 122.1 (2), 121.0
(23), 120.1 (1), 118.1 (10), 117.1 (100), 116.2 (6), 93.1 (7), 92.1
(3), 91.2 (1), 90.1 (9), 89.1 (9), 77.2 (1), 75.2 (1), 65.2 (12), 64.3
(3), 63.2 (5), 62.3 (1), 53.3 (1), 51.1 (1); IR (ATR) ν (cm−1) = 3200,
2952, 2855, 2704, 2563, 2324, 2213, 2086, 1940, 1795, 1748, 1639,
1602, 1539, 1499, 1452, 1387, 1349, 1299, 1252, 1207, 1154, 1106,
1039, 1015, 936, 891, 833, 748, 714; Anal. Calcd for C15H11NO2:
C, 75.94; H, 4.67; N, 5.90. Found: C, 75.98; H, 4.32; N, 5.71.
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59
60
(4-Chloro-2-hydroxyphenyl)(1H-indol-1-yl)methanone
(1e).
Purified by silica gel column chromatography; White solid;
Isolated yield: 878 mg, 74%; Rf (n-pentane/ethyl acetate = 15/1) =
0.40; mp 161-163 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.20
(s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.2 Hz, 1H), 7.55 (d,
J = 8.4 Hz, 1H), 7.42-7.38 (m, 2H), 7.34 (t, J = 7.2 Hz, 1H), 7.15
(d, J = 1.8 Hz, 1H), 6.97 (dd, J = 8.4, 1.8 Hz, 1H), 6.71 (d, J = 3.6
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.0, 162.3,
141.4, 136.0, 132.2, 130.8, 127.5, 125.3, 124.4, 121.3, 120.0,
118.9, 116.2, 114.6, 109.6; MS (EI+, 70 eV): m/z (%) = 273.0 (11),
272.0 (6), 271.0 (34) [M]+, 156.9 (6), 156.0 (2), 155.0 (18), 129.0
(1), 127.0 (3), 118.1 (10), 117.1 (100), 116.2 (7), 101.1 (2), 99.1
(7), 91.1 (1), 90.1 (7), 89.2 (8), 73.1 (2), 63.2 (6); IR (ATR) ν (cm−1)
= 3113, 2957, 2746, 2333, 2190, 2086, 2004, 1905, 1794, 1625,
1588, 1544, 1496, 1450, 1417, 1350, 1246, 1204, 1149, 1083, 1016,
910, 861, 824, 745, 718. Anal. Calcd for C15H10ClNO2: C, 66.31;
H, 3.71; N, 5.16. Found: C, 65.88; H, 3.64; N, 5.06. HRMS (ESI)
m/z : [M+]+ calcd for C15H10ClNO2, 271.0400.; found, 271.0395.
(5-Chloro-2-hydroxyphenyl)(1H-indol-1-yl)methanone
(1b).
Purified by silica gel column chromatography; White solid;
Isolated yield: 949 mg, 84%; Rf (n-pentane/ethyl acetate = 15/1) =
0.40; mp 161-162 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.21
(s, 1H), 8.24 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.2 Hz, 1H), 7.54 (d,
J = 9.0 Hz, 1H), 7.41-7.38 (m, 2H), 7.34 (t, J = 7.5 Hz, 1H), 7.15
(d, J = 1.8 Hz, 1H), 6.97 (dd, J = 8.7, 2.1 Hz, 1H), 6.71 (d, J = 3.6
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.0, 162.3,
141.4, 136.0, 132.2, 130.8, 127.4, 125.2, 124.4, 121.3, 119.9,
118.8, 116.2, 114.6, 109.6; MS (EI+, 70 eV): m/z (%) = 273.0 (11),
272.0 (7), 271.0 (34) [M]+, 156.9 (6), 155.0 (18), 127.0 (3), 118.1
(10), 117.1 (100), 116.2 (8), 99.1 (7), 90.1 (7), 89.1 (9), 63.2 (6),
62.2 (2), 53.3 (1); IR (ATR) ν (cm−1) = 3079, 2926, 2746, 2325,
2165, 2084, 1985, 1905, 1794, 1625, 1587, 1544, 1496, 1450,
1416, 1350, 1245, 1203, 1149, 1083, 1016, 911, 861, 824, 745, 719;
Anal. Calcd for C15H10ClNO2: C, 66.31; H, 3.71; N, 5.16. Found:
C, 66.08; H, 3.78; N, 5.06.
(5-Fluoro-1H-indol-1-yl)(2-hydroxyphenyl)methanone
(1f).
Purified by silica gel column chromatography; Gray solid; Isolated
yield: 505 mg, 50%; Rf (n-pentane/ethyl acetate = 8/1) = 0.40; mp
139-141 oC; 1H NMR (600 MHz, (CD3)2CO): δ (ppm) 9.87 (s, 1H),
8.25 (dd, J = 9.0, 4.2 Hz, 1H), 7.58 (dd, J = 7.8, 1.8 Hz, 1H), 7.55-
7.52 (m, 1H), 7.50 (d, J = 4.2 Hz, 1H), 7.28 (dd, J = 8.4, 2.4 Hz,
1H), 7.14-7.10 (m, 2H), 6.99 (t, J = 7.5 Hz, 1H ), 6.65 (d, J = 3.6
Hz, 1H); 13C{1H} NMR (151 MHz, (CD3)2CO): δ (ppm) 170.4,
161.5, 160.8, 159.2, 135.5, 132.5, 131.9, 131.8, 131.2, 129.4,
119.4, 118.7, 117.4, 117.3, 115.8, 113.0, 112.8, 108.9, 106.9,
106.7; MS (EI+, 70 eV): m/z (%) = 256.1 (16), 255.0 (100) [M]+,
136.1 (8), 135.0 (93), 133.9 (11), 122.1 (4), 121.0 (51), 108.1 (8),
107.0 (15), 93.1 (8), 65.2 (13), 63.1 (4); IR (ATR) ν (cm−1) = 3306,
2924, 2853, 2720, 2507, 2324, 2266, 2201, 2171, 2142, 2071, 2008,
1977, 1941, 1856, 1736, 1657, 1599, 1541, 1460, 1384, 1326, 1260,
1201, 1128, 1096, 949, 885, 856, 801, 755, 719; Anal. Calcd for
C15H10FNO2: C, 70.58; H, 3.95; N, 5.49. Found: C, 70.69; H, 4.01;
N, 5.40.
(2,3-Dihydroxyphenyl)(1H-indol-1-yl)methanone (1c).8 Purified
by silica gel column chromatography; Brown oil; Isolated yield:
1.121 g, 97%; Rf (n-pentane/ethyl acetate = 8/1) = 0.24; 1H NMR
(600 MHz, CDCl3): δ (ppm) 10.09 (s, 1H), 8.33 (d, J = 8.4 Hz, 1H),
7.64 (d, J = 7.8 Hz, 1H), 7.50 (d, J = 3.6 Hz, 1H), 7.42-7.40 (m,
1H), 7.36-7.34 (m, 1H), 7.20 (dd, J = 7.8, 1.2 Hz, 1H), 7.16-7.14
(m, 1H), 6.90 (t, J = 8.1 Hz, 1H), 6.90 (d, J = 3.6 Hz, 1H), 6.14 (s,
1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.4, 148.3,
145.8, 136.0, 130.8, 127.9, 125.0, 124.3, 122.1, 121.1, 119.8,
119.6, 116.4, 116.3, 109.2; MS (EI+, 70 eV): m/z (%) = 255.3 (4),
254.3 (24), 253.1 (100) [M]+, 138.2 (3), 137.2 (34), 136.1 (7), 118.2
(14), 117.2 (77), 116.2 (6), 109.2 (3), 107.2 (3), 90.3 (8), 89.2 (11),
81.3 (7), 64.3 (5), 56.5 (3), 55.7 (4), 45.3 (2); IR (ATR) ν (cm−1) =
3388, 2161, 1912, 1646, 1590, 1538, 1449, 1386, 1336, 1263, 1186,
1099, 1073, 1017, 964, 878, 848, 786, 743, 669; Anal. Calcd for
C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C, 70.15; H, 4.27;
N, 5.60.
(5-Chloro-1H-indol-1-yl)(2-hydroxyphenyl)methanone
(1g).
Purified by silica gel column chromatography; Brown solid;
Isolated yield: 1.175 g, 99%; Rf (n-pentane/ethyl acetate = 15/1) =
o
1
0.21; mp 132-135 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.86
(s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.59-7.57 (m, 2H) 7.54 (t, J = 7.8
Hz, 1H), 7.49 (dd, J = 3.6, 1.8 Hz, 1H), 7.34 (d, J = 9.0 Hz, 1H),
7.13 (d, J =8.4 Hz, 1H), 6.99 (t, J = 7.8 Hz, 1H), 6.63 (d, J = 3.6
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.5, 161.5,
135.6, 134.5, 132.0, 131.2, 129.8, 129.1, 125.3, 120.8, 119.4,
118.7, 117.2, 115.8, 108.4; MS (EI+, 70 eV): m/z (%) = 271.9 (11),
270.8 (69) [M]+, 152.8 (34), 151.9 (12), 150.9 (100), 149.9 (9),
122.9 (6), 122.0 (5), 120.9 (64), 93.1 (11), 89.1 (6), 65.2 (19), 63.2
(6); IR (ATR) ν (cm−1) = 3852, 3284, 2923, 2850, 2669, 2330,
2173, 2084, 1991, 1873, 1730, 1652, 1593, 1533, 1444, 1375, 1331,
1250, 1189, 1070, 943, 875, 797, 758, 712, 660; Anal. Calcd for
C15H10ClNO2: C, 66.31; H, 3.71; N, 5.16. Found: C, 66.08; H, 3.78;
N, 5.06.
(2-Hydroxy-5-methylphenyl)(1H-indol-1-yl)methanone
(1d).
Purified by silica gel column chromatography; White solid;
Isolated yield: 485 mg, 64%; Rf (n-pentane/ethyl acetate = 30/1) =
o
1
0.31; mp 131-133 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.71
(s, 1H), 8.27 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.8 Hz, 1H), 7.47 (d,
J = 3.6 Hz, 1H), 7.40-7.37 (m, 2H), 7.34-7.31 (m, 2H), 7.03 (d, J =
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The Journal of Organic Chemistry
(5-Bromo-1H-indol-1-yl)(2-hydroxyphenyl)methanone
(1h).
117.5, 116.3, 115.2, 109.2; MS (EI+, 70 eV): m/z (%) = 282.1 (4)
1
2
3
4
5
6
7
8
Purified by silica gel column chromatography; Light red solid;
Isolated yield: 1.246 g, 99%; Rf (n-pentane/ethyl acetate = 20/1) =
[M]+, 163.2 (9), 162.1 (100), 161.2 (3), 146.0 (2), 132.1 (12), 121.0
(13), 117.1 (4), 116.1 (52), 115.1 (4), 114.1 (4), 104.1 (13), 91.2
(1), 90.2 (4), 89.1 (29), 88.1 (3), 87.1 (3), 86.1 (2), 77.2 (3), 76.2
(3), 65.2 (3), 64.3 (2), 63.2 (10), 62.1 (5), 57.2 (2), 51.4 (2); IR
(ATR) ν (cm−1) = 3802, 3691, 3356, 3098, 3028, 2922, 2854, 2629,
2553, 2412, 2287, 2212, 2159, 2107, 2032, 1992, 1940, 1846, 1741,
1665, 1599, 1510, 1447, 1383, 1326, 1193, 1074, 949, 883, 824,
743; Anal. Calcd for C15H10N2O4: C, 63.83; H, 3.57; N, 9.93.
Found: C, 63.76; H, 3.70; N, 9.89.
o
1
0.29; mp 134-136 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.86
(s, 1H), 8.14 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 1.8 Hz, 1H), 7.57 (dd,
J = 7.8, 1.2 Hz, 1H), 7.55-7.52 (m, 1H), 7.49-7.47 (m, 2H), 7.13 (d,
J = 8.4 Hz, 1H), 7.00-6.97 (m, 1H), 6.62 (d, J = 3.6 Hz, 1H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.5, 161.6, 135.6,
134.8, 132.5, 131.2, 129.0, 127.9, 123.9, 119.4, 118.7, 117.6,
117.5, 115.8, 108.3; MS (EI+, 70 eV): m/z (%) = 315.0 (52) [M]+,
236.3 (3), 235.2 (4), 198.2 (7), 197.0 (100), 195.0 (91), 193.9 (4),
122.2 (6), 121.1 (78), 116.2 (17), 115.0 (26), 93.0 (18), 92.1 (3),
89.2 (7), 88.2 (3), 87.0 (3), 65.1 (26), 63.2 (8), 62.0 (5); IR (ATR)
ν (cm−1) = 3922, 3846, 3683, 3284, 3156, 3121, 3071, 2963, 2924,
2852, 2740, 2624, 2514, 2330, 2229, 2187, 2163, 2109, 2045, 2000,
1969, 1923, 1880, 1818, 1747, 1648, 1606, 1574, 1533, 1480, 1441,
1370, 1328, 1253, 1178, 1111, 1084, 1056, 1036, 979, 942, 882,
752, 692; Anal. Calcd for C15H10BrNO2: C, 56.99; H, 3.19; N, 4.43.
Found: C, 56.70; H, 3.23; N, 4.34.
9
1-(2-Hydroxybenzoyl)-1H-indole-5-carbonitrile (1l). Purified by
silica gel column chromatography; Yellow solid; Isolated yield:
571 mg, 48%; Rf (n-pentane/ethyl acetate = 5/1) = 0.13; mp 159-
161 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 9.83 (s, 1H), 8.32 (d,
J = 9.0 Hz, 1H), 7.97 (s, 1H), 7.64 (dd, J = 8.7, 1.5 Hz, 1H), 7.60
(d, J = 3.6 Hz, 1H), 7.58-7.56 (m, 2H), 7.16-7.14 (m, 1H), 7.02-
7.00 (m, 1H), 6.75 (d, J = 3.6 Hz, 1H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 170.7, 161.8, 138.0, 136.2, 131.1, 130.8, 130.0,
128.1, 126.1, 119.7, 119.6, 118.9, 117.0, 115.3, 108.4, 107.5; MS
(EI+, 70 eV): m/z (%) = 263.2 (14), 262.1 (84) [M]+, 143.2 (4),
142.1 (39), 135.1 (10), 122.2 (8), 121.0 (100), 120.1 (6), 115.1 (4),
114.1 (4), 93.1 (10), 92.1 (5), 65.2 (12), 64.2 (2), 63.2 (3); IR (ATR)
ν (cm−1) = 3854, 3320, 3158, 3064, 2923, 2853, 2727, 2535, 2324,
2171, 2104, 2014, 1985, 1935, 1898, 1857, 1655, 1606, 1577, 1540,
1459, 1371, 1330, 1250, 1193, 1158, 1090, 1032, 889, 819, 761,
724, 665; Anal. Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68.
Found: C, 73.39; H, 3.83; N, 11.25. HRMS (ESI) m/z : [M+Na]+
calcd for C16H10N2O2Na, 285.0635; found, 285.0631.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(2-Hydroxyphenyl)(5-methyl-1H-indol-1-yl)methanone
(1i).
Purified by silica gel column chromatography; White solid;
Isolated yield: 849 mg, 78%; Rf (n-pentane/ethyl acetate = 20/1) =
o
1
0.41; mp 143-144 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.95
(s, 1H), 8.15 (d, J = 8.4 Hz, 1H), 7.59 (dd, J = 8.1, 1.5 Hz, 1H),
7.53-7.50 (m, 1H), 7.43-7.41 (m, 2H), 7.21 (d, J = 8.4 Hz, 1H), 7.12
(d, J = 8.4 Hz, 1H), 6.97 (t, J = 7.5 Hz, 1H), 6.61 (d, J = 3.6 Hz,
1H), 2.48 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm)
170.5, 161.4, 135.2, 134.3, 134.0, 131.3, 131.1, 128.0, 126.4,
121.1, 119.3, 118.6, 116.2, 115.9, 109.1, 21.6; MS (EI+, 70 eV):
m/z (%) = 252.2 (12), 251.1 (77) [M]+, 235.1 (2), 132.2 (14), 131.2
(70), 130.6 (100), 129.2 (2), 128.1 (3), 122.2 (2), 121.1 (33), 103.2
(7), 102.0 (5), 93.0 (10), 92.0 (1), 78.2 (1), 77.2 (7), 76.2 (2), 65.2
(13), 64.3 (1), 63.1 (4), 51.0 (1); IR (ATR) ν (cm−1) = 3181, 2916,
2858, 2710, 2181, 2087, 2022, 1897, 1638, 1604, 1539, 1458, 1383,
1340, 1256, 1209, 1139, 1092, 1065, 1039, 1000, 953, 891, 834,
811, 760, 718; Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N,
5.57. Found: C, 76.10; H, 4.98; N, 5.50.
(4-Bromo-1H-indol-1-yl)(2-hydroxyphenyl)methanone
(1m).
Purified by silica gel column chromatography; White solid;
Isolated yield: 663 mg, 59%; Rf (n-pentane/ethyl acetate = 40/1) =
o
0.20; mp 114-116 C; 1H NMR (600 MHz, CDCl3): δ (ppm) 9.89
(s, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.58 (d, J = 7.8 Hz, 1H), 7.56-
7.52 (m, 2H), 7.49 (d, J = 7.8 Hz, 1H), 7.27-7.24 (m, 1H), 7.14 (d,
J = 8.4 Hz, 1H), 7.00 (t, J = 7.5 Hz, 1H ), 6.77 (d, J = 3.6 Hz, 1H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.8, 161.7, 136.4,
135.8, 131.5, 131.3, 128.5, 127.1, 126.1, 119.5, 118.8, 115.7,
115.2, 115.0, 108.8; MS (EI+, 70 eV): m/z (%) = 317.9 (8), 316.9
(48), 315.9 (9), 314.9 (84) [M]+, 197.9 (9), 196.9 (96), 195.9 (12),
194.9 (100), 120.9 (85), 115.9 (20), 114.9 (20), 113.9 (8), 92.9 (17),
91.9 (7), 89.0 (9), 87.9 (8), 65.0 (29), 64.0 (6), 63.0 (10); IR (ATR)
ν (cm−1) = 3254, 3111, 3057, 2923, 2854, 2660, 2325, 2200, 2114,
1995, 1926, 1854, 1784, 1725, 1646, 1606, 1578, 1529, 1471, 1421,
1380, 1329, 1278, 1237, 1150, 1053, 966, 878, 743, 680; Anal.
Calcd for C15H10BrNO2: C, 56.99; H, 3.19; N, 4.43. Found: C,
57.19; H, 3.28; N, 4.43.
(5-Hydroxy-1H-indol-1-yl)(2-hydroxyphenyl)methanone
(1j).
Purified by silica gel column chromatography; Gray solid; Isolated
yield: 304 mg, 53%; Rf (n-pentane/ethyl acetate = 8/1) = 0.08; mp
175-177 oC; 1H NMR (600 MHz, (CD3)2CO): δ (ppm) 9.26 (s, 1H),
8.28 (s, 1H), 8.22 (d, J = 9.0 Hz, 1H), 7.51 (dd, J = 7.5, 1.5 Hz,
1H), 7.48-7.45 (m, 1H), 7.23 (d, J = 3.6 Hz, 1H), 7.08-7.05 (m,
1H), 7.04-7.03 (m, 2H), 6.91 (dd, J = 9.0, 2.4 Hz, 1H), 6.54 (d, J =
3.6 Hz, 1H); 13C{1H} NMR (151 MHz, (CD3)2CO): δ (ppm) 167.4,
155.6, 155.5, 154.2, 154.1, 132.6, 132.4, 129.7, 129.6, 128.5,
121.8, 121.7, 119.7, 116.8, 116.7, 116.6, 113.2, 113.1, 108.1,
105.7, 105.7; MS (EI+, 70 eV): m/z (%) = 254.1 (18), 253.0 (84)
[M]+, 150.1 (10), 134.1 (10), 133.1 (100), 132.0 (13), 121.1 (49),
105.1 (5), 104.1 (7), 93.1 (7), 77.2 (6), 76.1 (4), 65.2 (12), 63.2 (4),
51.2 (8); IR (ATR) ν (cm−1) = 3281, 2927, 2852, 2782, 2623, 2553,
2476, 2323, 2172, 2048, 2007, 1947, 1915, 1869, 1795, 1652, 1605,
1549, 1450, 1370, 1261, 1228, 1184, 1144, 1106, 1063, 949, 888,
855, 828, 808, 717; Anal. Calcd for C15H11NO3: C, 71.14; H, 4.38;
N, 5.53. Found: C, 70.91; H, 4.32; N, 5.55.
(2-Hydroxyphenyl)(6-methyl-1H-indol-1-yl)methanone
(1n).
Purified by silica gel column chromatography; Light brown solid;
Isolated yield: 909 mg, 91%; Rf (n-pentane/ethyl acetate = 40/1) =
0.15; mp 86-89 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 9.98 (s,
1H), 8.13 (s, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.53-7.49 (m, 2H), 7.38
(d, J = 3.6 Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 7.12 (d, J =8.4 Hz,
1H), 6.98 (t, J = 7.5 Hz, 1H), 6.63 (d, J = 3.6 Hz, 1H), 2.52 (s, 3H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.8, 161.4, 136.5,
135.3, 131.3, 128.5, 127.4, 125.7, 120.8, 119.3, 118.6, 116.5,
116.3, 109.1, 22.1; MS (EI+, 70 eV): m/z (%) = 252.3 (16), 251.1
(72) [M]+, 249.9 (2), 235.1 (2), 196.2 (2), 132.3 (16), 130.9 (100),
130.1 (40), 129.2 (2), 128.1 (5), 122.2 (3), 121.1 (40), 103.2 (9),
102.0 (8), 93.0 (14), 78.2 (2), 77.1 (12), 75.2 (2), 65.1 (21), 63.0
(7), 52.9 (2), 50.8 (3); IR (ATR) ν (cm−1) = 3271, 3068, 3022, 2919,
2854, 2691, 2555, 2328, 2188, 2112, 1992, 1916, 1878, 1751, 1716,
1647, 1602, 1540, 1487, 1452, 1389, 1347, 1254, 1204, 1129, 1100,
1032, 937, 890, 807, 750, 713, 667; Anal. Calcd for C16H13NO2: C,
76.48; H, 5.21; N, 5.57. Found: C, 76.11; H, 5.20; N, 5.47.
(2-Hydroxyphenyl)(5-nitro-1H-indol-1-yl)methanone
(1k).
Purified by silica gel column chromatography; Yellow solid;
Isolated yield: 700 mg, 50%; Rf (n-pentane/ethyl acetate = 5/1) =
o
1
0.20; mp 191-193 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.83
(s, 1H), 8.56 (d, J = 2.4 Hz, 1H), 8.33 (d, J = 9.0 Hz, 1H), 8.28 (dd,
J = 8.7, 2.1 Hz, 1H), 7.64 (d, J = 3.6 Hz, 1H), 7.60-7.57 (m, 2H),
7.16 (dd, J = 8.7, 0.9 Hz, 1H), 7.03-7.01 (m, 1H), 6.84 (d, J = 3.6
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.7, 161.9,
144.6, 139.2, 136.4, 131.2, 130.8, 130.6, 120.2, 119.7, 119.0,
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Page 10 of 16
(2-Hydroxyphenyl)(7-methyl-1H-indol-1-yl)methanone
(1o).
Purified by silica gel column chromatography; Light yellow solid;
Isolated yield: 899 mg, 82%; Rf (n-pentane/ethyl acetate = 15/1) =
0.60; mp 95-96 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.72 (s,
1H), 7.76 (dd, J = 8.1, 1.5 Hz, 1H), 7.58-7.55 (m, 1H), 7.50 (d, J =
7.8 Hz, 1H), 7.33 (d, J = 3.6 Hz, 1H), 7.28-7.26 (m, 1H), 7.19 (d, J
= 7.2 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.99-6.97 (m, 1H), 6.67 (d,
J = 4.2 Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 171.4,
162.9, 136.4, 135.7, 132.1, 131.9, 129.4, 127.6, 125.8, 124.2,
119.5, 119.0, 118.7, 115.5, 108.6, 21.5; MS (EI+, 70 eV): m/z (%)
= 251.9 (10), 250.8 (47) [M]+, 250.1 (2), 132.0 (10), 131.0 (100),
130.0 (30), 129.0 (1), 127.9 (2), 122.0 (2), 120.9 (29), 103.0 (5),
102.0 (3), 93.1 (7), 92.1 (2), 77.2 (5), 65.2 (11), 63.2 (3), 51.3 (2);
IR (ATR) ν (cm−1) = 3838, 3677, 3471, 3131, 3063, 2951, 2651,
2319, 2205, 2154, 2039, 1930, 1734, 1644, 1533, 1477, 1406, 1338,
1259, 1195, 1075, 1042, 960, 886, 801, 765, 695; Anal. Calcd for
C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.55; H, 5.30;
N, 5.47.
136.7, 136.2, 136.2, 132.8, 130.1, 123.2, 122.7, 119.2, 118.4,
118.1, 118.1, 116.9, 114.1, 25.2, 23.5, 22.5, 21.2; MS (EI+, 70 eV):
1
2
3
4
5
6
7
8
m/z (%) = 292.4 (8), 291.1 (63) [M]+, 172.3 (14), 171.2 (100),
170.2 (8), 168.2 (7), 167.2 (5), 154.2 (2), 144.2 (5), 143.2 (46),
142.3 (4), 140.2 (2), 128.2 (2), 121.2 (19), 116.0 (2), 115.2 (5), 93.2
(5), 66.0 (7), 45.4 (3); IR (ATR) ν (cm−1) = 3283, 3054, 2932, 2849,
2161, 1933, 1643, 1605, 1479, 1454, 1363, 1307, 1247, 1203, 1150,
1110, 1054, 1032, 958, 926, 882, 821, 742, 659; Anal. Calcd for
C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 77.94; H, 5.53;
N, 4.87.
9
(2-Hydroxyphenyl)(2-methyl-1H-indol-1-yl)methanone
(1s).7a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Purified by silica gel column chromatography; Yellow oil; Isolated
yield: 351 mg, 82%; Rf (n-pentane/ethyl acetate = 20/1) = 0.67; 1H
NMR (600 MHz, CDCl3): δ (ppm) 10.56 (s, 1H), 7.57-7.54 (m,
1H), 7.50 (d, J = 7.8 Hz, 1H), 7.45 (dd, J = 7.8, 1.8 Hz, 1H), 7.18-
7.14 (m, 2H), 7.11-7.06 (m, 2H), 6.88-6.85 (m, 1H), 6.48 (s, 1H),
2.48 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 173.3,
162.4, 137.7, 137.4, 136.8, 133.0, 129.6, 122.8, 122.7, 120.1,
119.4, 118.5, 116.6, 113.6, 108.5, 15.1; MS (EI+, 70 eV): m/z (%)
= 252.2 (9), 251.1 (50) [M]+, 132.2 (11), 131.2 (100), 130.2 (34),
121.1 (21), 103.2 (5), 93.1 (6), 77.2 (4), 65.2 (11), 63.3 (3); IR
(ATR) ν (cm−1) = 3283, 3057, 2967, 2924, 2750, 2322, 2085, 1929,
1645, 1608, 1480, 1453, 1372, 1311, 1252, 1199, 1111, 1029, 972,
890, 857, 812, 745, 710, 659; Anal. Calcd for C16H13NO2: C, 76.48;
H, 5.21; N, 5.57. Found: C, 74.39; H, 4.96; N, 6.05. HRMS (ESI)
m/z : [M+Na]+ calcd for C16H13NO2Na, 274.0839; found,
274.0834.
(7,8-Dihydrocyclopenta[g]indol-1(6H)-yl)(2-hydrox-
phenyl)methanone (1p). Purified by silica gel column
chromatography; White solid; Isolated yield: 620 mg, 60%; Rf (n-
pentane/ethyl acetate = 20/1) = 0.70; mp 87-88 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 10.60 (s, 1H), 7.70 (dd, J = 8.1, 1.5 Hz, 1H),
7.56-7.53 (m, 1H), 7.43 (d, J = 7.8 Hz, 1H), 7.30 (d, J = 3.6 Hz,
1H), 7.27-7.26 (m, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.97 (t, J = 7.5
Hz, 1H), 6.66 (d, J = 3.6 Hz, 1H), 3.10-3.05 (m, 4H), 2.16-2.11 (m,
2H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.7, 162.6,
143.0, 136.0, 133.3, 132.0, 130.3, 129.9, 128.0, 120.9, 119.4,
119.1, 118.6, 115.6, 108.9, 34.0, 33.4, 25.7; MS (EI+, 70 eV): m/z
(%) = 278.1 (11), 277.0 (51) [M]+, 158.1 (13), 157.0 (100), 156.0
(28), 155.0 (5), 154.0 (13), 129.0 (7), 128.0 (7), 127.0 (5), 120.9
(24), 92.9 (6), 65.0 (10); IR (ATR) ν (cm−1) = 3875, 3436, 3125,
3058, 2959, 2925, 2870, 2834, 2322, 2170, 2089, 2019, 1995, 1967,
1867, 1812, 1741, 1645, 1606, 1535, 1483, 1413, 1383, 1340, 1260,
1234, 1196, 1152, 1096, 1063, 1034, 954, 933, 882, 806, 767, 722,
671; Anal. Calcd for C18H15NO2: C, 77.96; H, 5.45; N, 5.05. Found:
C, 77.56; H, 5.44; N, 4.98.
Ethyl
1-(2-hydroxybenzoyl)-1H-indole-2-carboxylate
(1t).
Purified by silica gel column chromatography; Colorless solid;
Isolated yield: 340 mg, 23%; Rf (n-pentane/ethyl acetate = 20/1) =
0.37; mp 103-104 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.63
(s, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.54-7.51 (m, 2H), 7.45 (s, 1H),
7.38 (t, J = 7.8 Hz, 1H), 7.29 (t, J = 7.5 Hz, 1H), 7.26 (dd, J = 8.1,
1.5 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.84 (t, J = 7.5 Hz, 1H), 4.13-
4.12 (m, 2H), 1.17 (t, J = 7.2 Hz, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 173.6, 162.4, 160.8, 138.7, 137.0, 131.2, 130.9,
127.4, 127.2, 123.4, 122.9, 119.8, 118.5, 117.6, 115.6, 113.3, 61.6,
14.0; MS (EI+, 70 eV): m/z (%) = 310.3 (11), 309.0 (99) [M]+,
264.0 (8), 236.2 (3), 190.2 (12), 189.1 (100), 144.2 (7), 143.2 (41),
121.1 (19), 116.2 (3), 115.2 (9), 93.3 (5), 92.2 (2), 89.2 (4), 66.0
(8). 45.3 (3); IR (ATR) ν (cm−1) = 3231, 3066, 2992, 2958, 2655,
2322, 2166, 2076, 1827, 1701, 1654, 1614, 1580, 1530, 1479, 1443,
1381, 1327, 1280, 1239, 1197, 1156, 1023, 962, 893, 860, 812, 752,
698; Anal. Calcd for C18H15NO4: C, 69.89; H, 4.89; N, 4.53. Found:
C, 69.34; H, 4.79; N, 4.38. HRMS (ESI) m/z : [M+Na]+ calcd for
C18H15NO4Na, 332.0893; found, 332.0892.
(2-Hydroxyphenyl)(2-phenyl-1H-indol-1-yl)methanone
(1q).7a
Purified by silica gel column chromatography; Yellow solid;
Isolated yield: 712 mg, 76%; Rf (n-pentane/ethyl acetate = 20/1) =
0.62; mp 135-137 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.56
(s, 1H), 7.65 (d, J = 7.2 Hz, 1H), 7.48 (d, J = 8.4 Hz, 1H), 7.44-
7.40 (m, 2H), 7.38-7.37 (m, 2H), 7.30-7.27 (m, 3H), 7.25-7.21 (m,
2H), 7.01 (d, J = 8.4 Hz, 1H), 6.85 (s, 1H), 6.70 (t, J = 7.5 Hz, 1H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 173.9, 162.4, 141.4,
138.3, 136.8, 132.7, 129.6, 128.7, 128.0, 124.3, 123.2, 121.1,
119.4, 118.1, 116.9, 113.9, 109.5; MS (EI+, 70 eV): m/z (%) =
314.2 (5), 313.2 (21) [M]+, 194.2 (23), 193.1 (100), 192.3 (11),
191.2 (5), 190.1 (4), 166.2 (3), 165.1 (18), 164.3 (3), 121.1 (27),
93.2 (9), 90.3 (4), 89.2 (5), 65.2 (15), 63.2 (4); IR (ATR) ν (cm−1)
= 3869, 3196, 3051, 2696, 2488, 2323, 2185, 2101, 1996, 1883,
1800, 1745, 1646, 1609, 1575, 1478, 1450, 1364, 1324, 1291, 1239,
1189, 1159, 1111, 1026, 965, 899, 864, 785, 752, 692, 664; Anal.
Calcd for C21H15NO2: C, 80.49; H, 4.83; N, 4.47. Found: C, 79.60;
H, 4.65; N, 4.30. HRMS (ESI) m/z : [M+Na]+ calcd for
C21H15NO2Na, 336.0995; found, 336.0997.
(2-Hydroxyphenyl)(3-methyl-1H-indol-1-yl)methanone
(1u).8
Purified by silica gel column chromatography; White solid;
Isolated yield: 844 mg, 84%; Rf (n-pentane/ethyl acetate = 20/1) =
o
1
0.41; mp 154-156 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.95
(s, 1H), 8.28 (d, J = 8.4 Hz, 1H), 7.61 (dd, J = 7.8, 1.8 Hz, 1H),
7.56 (d, J = 7.8 Hz, 1H), 7.51 (t, J = 8.4 Hz, 1H), 7.41-7.39 (m,
1H), 7.36-7.34 (m, 1H), 7.25 (s, 1H), 7.11 (dd, J = 8.4, 0.6 Hz, 1H),
6.99 (t, J = 8.1 Hz, 1H), 2.30 (d, J = 1.2 Hz, 3H); 13C{1H} NMR
(151 MHz, CDCl3): δ (ppm) 170.2, 161.2, 136.4, 135.0, 131.9,
131.2, 125.2, 124.7, 124.1, 119.2, 119.2, 118.6, 118.5, 116.5,
116.4, 9.9; MS (EI+, 70 eV): m/z (%) = 252.3 (9), 251.1 (61) [M]+,
132.2 (10), 131.2 (100), 130.2 (59), 129.2 (2), 128.2 (3), 122.2 (2),
121.2 (22), 103.2 (6), 102.2 (4), 93.3 (7), 92.3 (2), 77.3 (8), 76.3
(2), 66.0 (12), 65.3 (2), 64.4 (3), 54.9 (2), 45.4 (6); IR (ATR) ν
(cm−1) = 3232, 2915, 2858, 2714, 2569, 2320, 2078, 1915, 1650,
1598, 1449, 1355, 1254, 1213, 1099, 1044, 932, 875, 742. Anal.
Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.06;
H, 5.25; N, 5.47.
(2-Hydroxyphenyl)(1,2,3,4-tetrahydro-9H-carbazol-9-
yl)methanone (1r).7a Purified by silica gel column chromatography;
Yellow oil; Isolated yield: 971 mg, 74%; Rf (n-pentane/ethyl
acetate = 30/1) = 0.16; 1H NMR (600 MHz, CDCl3): δ (ppm) 10.38
(s, 1H), 7.54-7.51 (m, 1H), 7.50 (dd, J = 7.8, 1.8 Hz, 1H), 7.44 (d,
J = 7.8 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.20 (t, J = 7.5 Hz, 1H),
7.13-7.09 (m, 2H), 6.88-6.86 (m, 1H), 2.86-2.61 (m, 4H), 1.89-1.87
(m, 4H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 172.2, 161.8,
ACS Paragon Plus Environment

Page 11 of 16
The Journal of Organic Chemistry
1-(2-Hydroxybenzoyl)-1H-indole-3-carbonitrile (1v). Purified by
2007, 1926, 1795, 1689, 1599, 1513, 1451, 1395, 1350, 1308, 1252,
1
2
3
4
5
6
7
8
recrystal (a mixture of n-pentane and ethyl acetate used as the
recrystallization solvent); White solid; Yield: 575 mg, 47%; Rf (n-
pentane/ethyl acetate = 8/1) = 0.21; mp 161-164 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 9.68 (s, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.98
(s, 1H), 7.79 (d, J = 7.2 Hz, 1H), 7.62-7.59 (m, 1H), 7.52-7.46 (m,
3H), 7.17 (d, J = 8.4 Hz, 1H), 7.06-7.03 (m, 1H); 13C{1H} NMR
(151 MHz, CDCl3): δ (ppm) 170.0, 161.9, 136.8, 135.2, 134.8,
131.0, 128.2, 126.9, 125.6, 120.1, 120.0, 119.1, 116.3, 114.8,
113.9, 93.9; MS (EI+, 70 eV): m/z (%) = 264.2 (7), 263.3 (35),
262.6 (22), 262.0 (100) [M]+, 235.1 (5), 207.2 (6), 143.2 (4), 142.2
(29), 141.2 (6), 122.2 (15), 121.1 (98), 120.2 (6), 115.2 (5), 114.2
(10), 93.2 (13), 92.2 (7), 66.0 (19), 64.3 (5), 45.3 (10); IR (ATR) ν
(cm−1) = 3779, 3314, 3143, 3068, 2924, 2689, 2233, 2079, 1989,
1919, 1803, 1765, 1703, 1605, 1547, 1499, 1453, 1343, 1309, 1257,
1205, 1153, 1123, 1097, 1025, 945, 882, 848, 744, 704, 658; Anal.
Calcd for C16H10N2O2: C, 73.27; H, 3.84; N, 10.68. Found: C,
73.27; H, 3.84; N, 10.75.
1208, 1145, 1088, 1008, 916, 881, 837, 740; Anal. Calcd for
C14H10N2O2: C, 70.58; H, 4.23; N, 11.76. Found: C, 70.54; H, 4.46;
N, 11.15. HRMS (ESI) m/z : [M+H]+ calcd for C14H11N2O2,
239.0815; found, 239.0813.
(1H-indol-1-yl)(2-nitrophenyl)methanone (1Y).16e Prepared
according to literature procedure.1 A solution of indole (1.172 g,
10.0 mmol), tetrabutylammonium hydrogensulfate (61.2 mg, 0.18
mmol), powdered NaOH (1.2 g, 30.0 mmol), 2-nitrobenzoyl
chloride (1.98 mL, 15.0 mmol), in CH2Cl2 (30 mL) were stirred in
a flask under air at room temperature for 5 h. The reaction mixture
was washed with water (30 mL) and extracted with CH2Cl2 (3×30
mL). The combined organic layer was dried with Na2SO4. Then the
solvent was evaporated under vacuum. The residue was purified by
flash chromatography on silica gel with n-pentane/ethyl acetate
(10:1) as the solvent to afford the pure product. Brown solid;
Isolated yield: 2.18 g, 82%; Rf (n-pentane/ethyl acetate = 10/1) =
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
0.14; mp 110-113 C; H NMR (400 MHz, CDCl3): δ (ppm) 8.59
(br s, 1H), 8.33 (d, J = 8.0 Hz, 1H), 7.84 (t, J = 7.4 Hz, 1H), 7.75
(t, J = 7.8 Hz, 1H), 7.64-7.59 (m, 2H), 7.41-7.32 (m, 2H), 6.82 (br
s, 1H), 6.61 (s, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm)
164.9, 145.6, 135.8, 134.6, 131.4, 131.3, 130.8, 128.9, 125.6,
125.5, 125.0, 124.5, 121.2, 116.7, 110.3; MS (EI+, 70 eV): m/z (%)
= 267.4 (10), 266.4 (62) [M]+, 233.3 (3), 220.3 (3), 191.2 (4), 190.2
(4), 165.2 (3), 163.1 (3), 151.2 (8), 150.2 (100), 135.2 (4), 134.1
(5), 133.1 (3), 132.2 (34), 117.2 (5), 116.1 (32), 104.1 (18), 92.1
(3), 90.1 (5), 89.1 (25), 79.2 (3), 78.2 (9), 77.1 (6), 76.2 (30), 75.1
(5), 74.1 (3), 64.1 (4), 63.2 (14), 62.1 (3), 52.1 (7), 51.2 (35), 50.1
(12); IR (ATR) ν (cm−1) = 3869, 3364, 3151, 3121, 3049, 2922,
2856, 2659, 2323, 2203, 2174, 2018, 1912, 1737, 1686, 1583, 1521,
1476, 1448, 1382, 1344, 1242, 1208, 1150, 1097, 1055, 1013, 985,
871, 846, 746, 710; Anal. Calcd for C15H10N2O3: C, 67.67; H, 3.79;
N, 10.52. Found: C, 67.77; H, 3.65; N, 10.37.
Methyl 1-(2-hydroxybenzoyl)-1H-indole-3-carboxylate (1w).
Purified by silica gel column chromatography; White solid;
Isolated yield: 433 mg, 49%; Rf (n-pentane/ethyl acetate = 10/1) =
o
1
0.20; mp 145-147 C; H NMR (600 MHz, CDCl3): δ (ppm) 9.85
(s, 1H), 8.22-8.19 (m, 2H), 8.12 (s, 1H), 7.59-7.56 (m, 2H), 7.44-
7.43 (m, 2H), 7.15 (d, J = 8.4 Hz, 1H), 7.03 (t, J = 7.5 Hz, 1H), 3.94
(s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.9, 164.5,
161.9, 136.4, 136.3, 133.6, 131.2, 127.7, 125.8, 125.2, 122.0,
119.9, 118.9, 115.9, 115.2, 113.8, 51.8; MS (EI+, 70 eV): m/z (%)
= 296.3 (10), 295.0 (82) [M]+, 264.0 (6), 176.3 (13), 175.2 (100),
174.4 (4), 146.2 (4), 145.2 (6), 144.2 (57), 143.3 (4), 121.2 (32),
116.2 (8), 115.2 (4), 93.3 (6), 89.2 (5), 66.0 (8), 64.4 (2), 45.4 (3);
IR (ATR) ν (cm−1) = 3408, 3150, 3053, 2952, 2319, 2165, 2088,
2015, 1917, 1667, 1609, 1552, 1483, 1446, 1362, 1325, 1278, 1245,
1188, 1151, 1033, 970, 933, 883, 812, 758, 658; Anal. Calcd for
C17H13NO4: C, 69.15; H, 4.44; N, 4.74. Found: C, 69.12; H, 4.29;
N, 4.43.
(2-Aminophenyl)(1H-indol-1-yl)methanone (1zb).16f A solution of
(1H-indol-1-yl)(2-nitrophenyl)methanone (532 mg, 2.0 mmol),
iron dust (560 mg, 10.0 mmol), 32% HCl (2.0 mL) in CH3CH2OH
(8 mL) were stirred in a flask under air at 120 ℃ for 2 h. The solvent
was removed in vacuo. The mixture was washed with water (10
mL) and extracted with CH2Cl2 (3×10 mL). The combined organic
layer was dried with Na2SO4. Then the solvent was evaporated
under vacuum. The residue was purified by flash chromatography
on silica gel with n-pentane/ethyl acetate (4:1) as the solvent to
afford the pure product. Yellow oil; Isolated yield: 417 mg, 88%;
(2-Hydroxyphenyl)(1H-pyrrol-1-yl)methanone (1y). Purified by
silica gel column chromatography; Light yellow oil; Isolated yield:
867 mg, 93%; Rf (n-pentane/ethyl acetate = 15/1) = 0.50; 1H NMR
(600 MHz, CDCl3): δ (ppm) 10.01 (s, 1H), 7.67 (dd, J = 7.8, 1.8
Hz, 1H), 7.54-7.51 (m, 1H), 7.34 (t, J = 2.4 Hz, 2H), 7.10 (dd, J =
8.4, 0.6 Hz, 1H), 6.98- 6.96 (m, 1H), 6.40 (t, J = 2.4 Hz, 2H);
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 170.0, 161.8, 135.8,
131.4, 121.8, 119.3, 118.5, 115.0, 113.6; MS (EI+, 70 eV): m/z (%)
= 188.3 (12), 187.2 (100) [M]+, 185.9 (3), 170.1 (2), 130.1 (1),
122.2 (7), 121.0 (88), 120.1 (7), 94.1 (1), 93.2 (13), 92.1 (11), 77.2
(1), 68.2 (2), 67.2 (32), 66.3 (2), 65.1 (21), 64.2 (2), 63.0 (7), 53.0
(2); IR (ATR) ν (cm−1) = 3880, 3319, 3150, 2665, 2334, 2083,
1992, 1927, 1652, 1609, 1580, 1464, 1406, 1339, 1242, 1183, 1154,
1082, 1036, 972, 885, 816, 740, 711, 671; Anal. Calcd for
C11H9NO2: C, 70.58; H, 4.85; N, 7.48. Found: C, 69.63; H, 4.81;
N, 7.67. HRMS (ESI) m/z : [M+]+ calcd for C11H9NO2, 187.0628;
found, 187.0632.
1
Rf (n-pentane/ethyl acetate = 4/1) = 0.80; H NMR (600 MHz,
CDCl3): δ (ppm) 8.30 (d, J = 8.4 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H),
7.39-7.35 (m, 3H), 7.34-7.29 (m, 2H), 6.79 (t, J = 8.4 Hz, 1H), 6.76-
6.73 (m, 1H), 6.61 (d, J = 4.2 Hz, 1H), 5.05 (s, 2H); 13C{1H} NMR
(151 MHz, CDCl3): δ (ppm) 169.4, 149.1, 136.2, 133.4, 131.5,
131.0, 128.2, 124.7, 123.8, 121.0, 117.2, 116.8, 116.3, 108.1; MS
(EI+, 70 eV): m/z (%) = 237.4 (8), 236.4 (41) [M]+, 235.5 (2), 121.2
(8), 120.2 (100), 119.3 (3), 117.2 (14), 116.2 (56), 92.2 (27), 91.2
(3), 90.2 (6), 89.2 (29), 65.3 (19), 64.3 (4), 63.2 (13), 62.3 (3), 52.3
(3); IR (ATR) ν (cm−1) = 3873, 3475, 3378, 3117, 3044, 2649,
2495, 2320, 2172, 2084, 2004, 1901, 1748, 1659, 1616, 1565, 1529,
1486, 1445, 1380, 1318, 1242, 1205, 1145, 1123, 1016, 976, 940,
913, 878, 857, 857, 822, 745, 675; Anal. Calcd for C15H12N2O: C,
76.25; H, 5.12; N, 11.86. Found: C, 75.78; H, 4.82; N, 11.88.
(1H-benzo[d]imidazol-1-yl)(2-hydroxyphenyl)methanone (1z).
Purified by recrystal; White solid; Isolated yield: 76 mg, 16%; Rf
o
1
(n-pentane/ethyl acetate = 4/1) = 0.09; mp 120-122 C; H NMR
(600 MHz, CDCl3): δ (ppm) 9.94 (s, 1H), 8.34 (s, 1H), 8.09-8.07
(m, 1H), 7.87-7.86 (m, 1H), 7.63-7.60 (m, 2H), 7.48-7.44 (m, 2H),
7.19-7.19 (m, 1H), 7.05 (t, J = 7.5 Hz, 1H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 169.5, 162.0, 144.1, 143.0, 136.8, 132.2,
131.0, 126.0, 125.6, 120.9, 120.0, 119.0, 115.3, 115.0; MS (EI+, 70
eV): m/z (%) = 239.4 (3), 238.3 (30) [M]+, 237.4 (3), 122.2 (5),
121.2 (100), 120.2 (29), 119.2 (3), 118.2 (52), 93.2 (13), 92.2 (21),
91.2 (4), 90.2 (10), 65.2 (21), 64.2 (9), 63.2 (11); IR (ATR) ν (cm−1)
= 3371, 3124, 3060, 2921, 2855, 2696, 2589, 2321, 2176, 2083,
N-(2-(1H-indole-1-carbonyl)phenyl)-4-
methylbenzenesulfonamide
(1zc).
A
solution
of
(2-
aminophenyl)(1H-indol-1-yl)methanone (449 mg, 1.90 mmol),
pyridine(0.19 mL, 2.28 mmol), 4-Methylbenzenesulfonyl chloride
(2.28 mmol, 435 mg) in CH2Cl2 (12 mL) were stirred in a flask
under air at room temperature for 8 h. The mixture was washed with
water (20 mL) and extracted with CH2Cl2 (3×20 mL). The
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The Journal of Organic Chemistry
Page 12 of 16
combined organic layer was dried with Na2SO4. Then the solvent
7.12-7.08 (m, 2H), 6.11 (t, J = 7.5 Hz, 1H), 5.47 (s, 1H), 3.63 (dd,
1
2
3
4
5
6
7
8
was evaporated under vacuum. The residue was purified by flash
chromatography on silica gel with n-pentane/ethyl acetate (8:1) as
the solvent to afford the pure product. White solid; Isolated yield:
408 mg, 55%; Rf (n-pentane/ethyl acetate = 8/1) = 0.25; mp 140-
141 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.54 (s, 1H), 8.19 (d,
J = 7.8 Hz, 1H), 7.82 (d, J = 8.4 Hz, 1H), 7.59-7.56 (m, 2H), 7.45
(d, J = 8.4 Hz, 2H), 7.39-7.33 (m, 3H), 7.24 (t, J = 7.5 Hz, 1H),
6.77 (d, J = 7.8 Hz, 2H ), 6.64 (d, J = 4.2 Hz, 1H), 6.46 (d, J = 3.6
Hz, 1H), 2.06 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm)
167.5, 144.0, 137.4, 135.8, 135.7, 133.1, 130.7, 130.3, 129.5,
127.4, 127.1, 126.6, 126.0, 125.4, 125.0, 124.6, 121.0, 116.7,
108.9, 21.4; MS (EI+, 70 eV): m/z (%) = 391.4 (4), 390.4 (13) [M]+,
275.3 (4), 274.3 (25), 273.2 (10), 236.4 (9), 235.4 (54), 234.3 (8),
210.3 (15), 209.3 (22), 208.2 (5), 195.3 (3), 180.3 (5), 167.2 (6),
166.1 (3), 155.2 (4), 119.1 (20), 118.1 (11), 117.2 (100), 116.1 (3),
92.2 (19), 91.1 (32), 90.1 (5), 89.1 (7), 65.2 (8), 64.2 (4), 63.2 (4);
IR (ATR) ν (cm−1) = 3879, 3276, 3152, 3054, 2922, 2855, 2668,
2322, 2173, 2087, 1978, 1916, 1809, 1744, 1650, 1595, 1539, 1484,
1448, 1399, 1334, 1275, 1243, 1201, 1183, 1157, 1089, 1062, 1016,
954, 914, 861, 807, 759, 713, 675; Anal. Calcd for C22H18N2O3S:
C, 67.68; H, 4.65; N, 7.17. Found: C, 67.81; H, 4.64; N, 7.05.
J = 16.8, 8.4 Hz, 1H), 3.53 (dd, J = 16.8, 6.6Hz, 1H); 13C{1H}
NMR (151 MHz, CDCl3): δ (ppm) 159.1, 144.4, 144.1, 140.5,
128.6, 126.8, 124.9, 124.5, 123.7, 120.4, 120.3, 119.7, 115.5, 90.4,
35.3; MS (EI+, 70 eV): m/z (%) = 254.3 (14), 253.1 (100) [M]+,
251.9 (3), 137.2 (7), 136.2 (42), 119.3 (4), 118.3 (46), 117.3 (68),
108.2 (10), 107.2 (5), 91.3 (4), 90.3 (15), 89.3 (15), 80.3 (8), 79.3
(4), 64.5 (4), 56.5 (3), 55.8 (13), 54.9 (7), 54.2 (3), 45.4 (4); IR
(ATR) ν (cm−1) = 3858, 3626, 3218, 2919, 2851, 2681, 2507, 2326,
2077, 1987, 1918, 1777, 1645, 1588, 1463, 1335, 1297, 1255, 1172,
1065, 978, 923, 890, 849, 805, 736, 672; Anal. Calcd for
C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C, 71.61; H, 4.59;
N, 5.41; HRMS (ESI) m/z: [M+Na]+ calcd for C15H11NO3Na,
276.0631; found, 276.0631.
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10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
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56
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59
60
2-Methyl-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2d). Purified by silica gel column
chromatography; White solid; Isolated yield: 112 mg, 89%; Rf (n-
pentane/ethyl acetate = 30/1) = 0.19; mp 139-142 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.14 (d, J = 7.8 Hz, 1H), 7.86 (d, J = 1.8
Hz, 1H), 7.30-7.26 (m, 3H), 7.08 (t, J = 7.5 Hz, 1H), 6.96 (d, J =
7.8 Hz, 1H), 6.02 (t, J = 7.5 Hz, 1H), 3.58 (dd, J = 16.8 Hz, 1H),
3.45 (dd, J = 16.5 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 159.5, 154.8, 140.6, 135.3, 133.0, 128.5, 128.3,
127.3, 124.9, 124.2, 119.5, 116.6, 115.5, 89.6, 35.3, 20.8; MS (EI+,
70 eV): m/z (%) = 252.3 (14), 251.2 (100) [M]+, 135.3 (12), 134.2
(47), 125.6 (3), 118.3 (5), 117.2 (58), 106.3 (10), 105.3 (9), 90.3
(9), 89.3 (10), 78.3 (9), 77.3 (4), 55.8 (4), 54.9 (3); IR (ATR) ν
(cm−1) = 3857, 3309, 3196, 3033, 2918, 2858, 2727, 2324, 2086,
1990, 1867, 1653, 1604, 1483, 1426, 1306, 1229, 1143, 1069, 1031,
913, 856, 817, 745, 706, 663; Anal. Calcd for C16H13NO2: C, 76.48;
H, 5.21; N, 5.57. Found: C, 76.46; H, 5.13; N, 5.45; HRMS (ESI)
m/z: [M+Na]+ calcd for C16H13NO2Na, 274.0839; found, 274.0838.
5a,6-Dihydro-12H-benzo[5,6][1,3]oxazino[3,2-a]indol-12-one
(2a).8 Purified by silica gel column chromatography; White solid;
Isolated yield: 103 mg, 87%; Rf (n-pentane/ethyl acetate = 30/1) =
o
1
0.12; mp 127-128 C; H NMR (400 MHz, CDCl3): δ (ppm) 8.12
(d, J = 7.6 Hz, 1H), 8.06 (d, J = 8.0 Hz, 1H), 7.48 (t, J = 7.8 Hz,
1H), 7.30-7.24 (m, 2H), 7.18 (t, J = 7.6 Hz, 1H), 7.09-7.04 (m, 2H),
6.06-6.01 (m, 1H), 3.57 (dd, J = 16.6, 8.2 Hz, 1H), 3.45 (dd, J =
16.4, 7.6 Hz, 1H); 13C{1H} NMR (101 MHz, CDCl3): δ (ppm)
159.2, 156.8, 140.5, 134.5, 128.5, 127.2, 124.9, 124.3, 123.4,
119.9, 116.9, 115.4, 89.6, 35.3; MS (EI+, 70 eV): m/z (%) = 238.1
(21), 237.1 (100) [M]+, 121.1 (13), 120.1 (30), 118.2 (9), 117.1
(71), 116.3 (3), 92.2 (17), 90.2 (9), 89.2 (9), 77.2 (1), 76.1 (1), 65.3
(2), 64.3 (5), 63.3 (6); IR (ATR) ν (cm−1) = 3882, 3324, 3196, 3049,
2922, 2855, 2656, 2317, 2171, 2090, 2007, 1890, 1819, 1659, 1600,
1474, 1315, 1225, 1184, 1149, 1081, 1021, 938, 857, 798, 746, 689;
Anal. Calcd for C15H11NO2: C, 75.94; H, 4.67; N, 5.90. Found: C,
74.81; H, 4.29; N, 6.04; HRMS (ESI) m/z : [M+Na]+ calcd for
C15H11NO2Na, 260.0682; found, 260.0680.
3-Chloro-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2e). Purified by silica gel column chromatography;
White solid; Isolated yield: 100 mg, 74%; Rf (n-pentane/ethyl
o
1
acetate = 10/1) = 0.56; mp 158-159 C; H NMR (600 MHz,
CDCl3): δ (ppm) 8.10 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H),
7.31-7.26 (m, 2H), 7.17 (dd, J = 8.4, 1.8 Hz, 1H), 7.11-7.08 (m,
2H), 6.06 (t, J = 7.8 Hz, 1H), 3.59 (dd, J = 16.5, 8.1 Hz, 1H), 3.47
(dd, J = 16.5, 6.9 Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ
(ppm) 158.5, 157.3, 140.4, 140.2, 129.6, 128.6, 127.0, 125.0, 124.5,
124.0, 118.4, 117.4, 115.5, 90.0, 35.2; MS (EI+, 70 eV): m/z (%) =
272.8 (12), 271.9 (6), 270.8 (39) [M]+, 155.9 (6), 154.9 (12), 153.8
(17), 127.9 (8), 125.9 (24), 118.0 (9), 117.0 (100), 116.0 (7), 98.0
(9), 91.1 (6), 90.1 (26), 89.1 (29), 63.2 (24), 62.2 (6); IR (ATR) ν
(cm−1) = 3882, 3327, 3061, 2924, 2681, 2322, 2180, 2106, 1993,
1920, 1788, 1728, 1659, 1597, 1479, 1429, 1305, 1223, 1177, 1071,
944, 867, 751, 662; Anal. Calcd for C15H10ClNO2: C, 66.31; H,
3.71; N, 5.16. Found: C, 65.52; H, 3.51; N, 5.10; HRMS (ESI) m/z:
[M+Na]+ calcd for C15H10ClNO2Na, 294.0292; found, 294.0291.
2-Chloro-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2a]indol-
12-one (2b). Purified by silica gel column chromatography; White
solid; Isolated yield: 92 mg, 68%; Rf (n-pentane/ethyl acetate =
10/1) = 0.56; mp 159-161 oC; 1H NMR (600 MHz, CDCl3): δ (ppm)
8.10 (d, J = 7.8 Hz, 1H), 8.00 (d, J = 8.4 Hz, 1H), 7.30-7.26 (m,
2H), 7.17 (dd, J = 8.4, 1.8 Hz, 1H), 7.11-7.08 (m, 2H), 6.06 (t, J =
7.8 Hz, 1H), 3.59 (dd, J = 16.5, 8.1 Hz, 1H), 3.46 (dd, J = 16.5, 6.9
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 158.5, 157.3,
140.4, 140.2, 129.6, 128.6, 127.0, 125.0, 124.5, 124.0, 118.4,
117.4, 115.5, 90.0, 35.2; MS (EI+, 70 eV): m/z (%) = 273.2 (40),
272.3 (28), 271.0 (100) [M]+, 269.9 (3), 157.1 (3), 156.2 (5), 155.2
(9), 154.1 (13), 128.1 (3), 126.1 (9), 118.2 (7), 117.2 (65), 98.2 (3),
90.3 (12), 89.3 (12), 64.3 (8); IR (ATR) ν (cm−1) = 3881, 3326,
3057, 2926, 2851, 2674, 2324, 2176, 2108, 1993, 1897, 1722, 1659,
1594, 1477, 1430, 1304, 1224, 1172, 1072, 947, 866, 752, 662;
Anal. Calcd for C15H10ClNO2: C, 66.31; H, 3.71; N, 5.16. Found:
C, 65.77; H, 3.68; N, 4.97; HRMS (ESI) m/z: [M+Na]+ calcd for
C15H10ClNO2Na, 294.0292; found, 294.0292.
8-Chloro-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2a]indol-
12-one (2g). Purified by silica gel column chromatography; White
solid; Isolated yield: 94 mg, 69%; Rf (n-pentane/ethyl acetate =
30/1) = 0.10; mp 148-151 oC; 1H NMR (600 MHz, CDCl3): δ (ppm)
8.06-8.04 (m, 2H), 7.52-7.49 (m, 1H), 7.26-7.24 (m, 2H), 7.20 (t, J
= 7.5 Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.05 (t, J = 7.5 Hz, 1H),
3.57 (dd, J = 16.8, 7.8 Hz, 1H), 3.45 (dd, J = 16.8, 7.2 Hz, 1H).
13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 159.1, 156.8, 139.2,
134.7, 129.2, 129.1, 128.5, 125.2, 123.5, 119.6, 117.0, 116.2, 89.6,
35.1; MS (EI+, 70 eV): m/z (%) = 272.3 (28), 271.0 (100) [M]+,
153.1 (11), 152.3 (3), 151.1 (32), 121.2 (12), 120.2 (31), 116.2 (4),
92.2 (15), 89.2 (9), 65.2 (3), 64.3 (6); IR (ATR) ν (cm−1) = 3313,
3131, 3071, 2921, 2659, 2332, 2056, 2013, 1881, 1736, 1659, 1603,
1469, 1431, 1403, 1359, 1330, 1308, 1241, 1216, 1188, 1150, 1109,
4-Hydroxy-5a,6-dihydro-12H-
benzo[5,6][1,3]oxazino[3,2a]indol-12-one (2c).8 Purified by silica
gel column chromatography; White solid; Isolated yield: 86 mg,
68%; Rf (n-pentane/ethyl acetate = 8/1) = 0.08; mp 231-233 oC; 1H
NMR (600 MHz, CDCl3): δ (ppm) 8.15 (d, J = 7.8 Hz, 1H), 7.62
(dd, J = 7.8, 1.2 Hz, 1H), 7.32-7.28 (m, 2H), 7.16-7.15 (m, 1H),
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Page 13 of 16
The Journal of Organic Chemistry
1070, 1026, 951, 864, 819, 789, 729, 698, 656; Anal. Calcd for
7-Bromo-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
1
2
3
4
5
6
7
8
C15H10ClNO2: C, 66.31; H, 3.71; N, 5.16. Found: C, 66.11; H, 3.64;
N, 4.75; HRMS (ESI) m/z: [M+Na]+ calcd. for C15H10ClNO2Na,
294.0292; found, 294.0293.
a]indol-12-one (2m). Purified by silica gel column
chromatography; White solid; Isolated yield: 41 mg, 26%; Rf (n-
pentane/ethyl acetate = 40/1) = 0.18; mp 165-166 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.07 (d, J = 7.8 Hz, 1H), 7.53 (t, J = 7.8 Hz,
1H), 7.24-7.17 (m, 3H), 7.09 (d, J = 8.4 Hz, 1H), 6.08 (t, J = 7.5
Hz, 1H), 3.61 (dd, J = 17.4, 8.4 Hz, 1H ), 3.43 (dd, J = 17.4, 6.6
Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 159.4, 156.8,
141.5, 134.8, 130.3, 128.6, 128.2, 127.1, 123.6, 119.6, 119.4,
117.1, 114.0, 88.9, 36.7; MS (EI+, 70 eV): m/z (%) = 316.0 (6),
315.0 (38) [M]+, 196.9 (30), 194.9 (32), 121.0 (30), 119.9 (100),
117.0 (8), 115.9 (21), 93.0 (7), 91.9 (69), 89.0 (25), 65.1 (8), 64.0
(26), 63.0 (37), 62.0 (9), 51.0 (8); IR (ATR) ν (cm−1) = 3326, 3042,
2923, 2854, 2320, 2169, 2082, 2022, 1993, 1924, 1842, 1662, 1600,
1478, 1452, 1413, 1364, 1319, 1239, 1178, 1152, 1110, 1085, 1026,
938, 886, 850, 814, 759, 706, 659; Anal. Calcd for C15H10BrNO2:
C, 56.99; H, 3.19; N, 4.43. Found: C, 57.46; H, 3.13; N, 4.37;
HRMS (ESI) m/z: [M+Na]+ calcd for C15H10BrNO2Na, 337.9787;
found, 337.9789.
8-Bromo-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2h). Purified by silica gel column
chromatography; White solid; Isolated yield: 89 mg, 57%; Rf (n-
pentane/ethyl acetate = 40/1) = 0.24; mp 164-167 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.06 (dd, J = 7.8, 1.2 Hz, 1H), 8.01 (d, J =
7.8 Hz, 1H), 7.53-7.51 (m, 1H), 7.42-7.40 (m, 2H), 7.21 (t, J = 8.1
Hz, 1H), 7.07 (d, J = 8.4 Hz, 1H), 6.06 (t, J = 7.5 Hz, 1H), 3.59 (dd,
J = 16.8, 7.8 Hz, 1H), 3.47 (dd, J = 16.5, 6.9 Hz, 1H); 13C{1H}
NMR (151 MHz, CDCl3): δ (ppm) 159.2, 156.8, 139.6, 134.7,
131.4, 129.5, 128.5, 128.1, 123.6, 119.6, 117.0, 116.7, 89.6, 35.0;
MS (EI+, 70 eV): m/z (%) = 316.1 (2), 315.0 (85) [M]+, 314.2 (3),
236.2 (2), 198.1 (3), 197.0 (41), 196.2 (2), 195.1 (39), 121.2 (14),
120.1 (44), 116.1 (17), 93.2 (2), 92.1 (18), 89.1 (10), 65.3 (2), 64.3
(5), 63.3 (7), 62.2 (3), 50.2 (2); IR (ATR) ν (cm−1) = 3314, 3131,
3069, 2917, 2655, 2328, 2174, 2087, 1986, 1879, 1658, 1602, 1469,
1428, 1401, 1359, 1329, 1307, 1241, 1216, 1187, 1150, 1110, 1083,
1025, 933, 869, 818, 789, 757, 729, 697, 655; Anal. Calcd for
C15H10BrNO2: C, 56.99; H, 3.19; N, 4.43. Found: C, 56.58; H, 3.15;
N, 4.35; HRMS (ESI) m/z: [M+Na]+ calcd for C15H10BrNO2Na,
337.9787; found, 337.9787.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
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53
54
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56
57
58
59
60
9-Methyl-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2n). Purified by silica gel column
chromatography; Colorless solid; Isolated yield: 92 mg, 73%; Rf
(n-pentane/ethyl acetate = 20/1) = 0.39; mp 166-169 oC; 1H NMR
(600 MHz, CDCl3): δ (ppm) 8.07 (dd, J = 7.8, 1.8 Hz, 1H), 7.99 (s,
1H), 7.51-7.48 (m, 1H), 7.19 (t, J = 7.8 Hz, 1H), 7.14 (d, J = 7.8
Hz, 1H), 7.06 (d, J = 8.4 Hz, 1H), 6.90 (d, J = 7.8 Hz, 1H), 6.03 (t,
J = 7.5 Hz, 1H), 3.54 (dd, J = 16.2, 7.8 Hz, 1H), 3.41 (dd, J = 16.2,
7.2 Hz, 1H), 2.38 (s, 3H); 13C{1H} NMR (151 MHz, CDCl3): δ
(ppm) 159.2, 156.9, 140.6, 138.6, 134.4, 128.5, 125.0, 124.5, 124.2,
123.3, 119.9, 116.9, 116.2, 89.9, 35.0, 21.8; MS (EI+, 70 eV): m/z
(%) = 252.2 (37), 251.1 (100) [M]+, 250.1 (5), 132.2 (18), 131.2
(85), 130.2 (77), 128.1 (3), 125.6 (4), 121.2 (23), 120.1 (34), 104.2
(4), 103.2 (16), 102.1 (7), 93.2 (6), 92.1 (36), 89.1 (3), 78.3 (8),
77.2 (15), 76.2 (3), 65.3 (6), 63.2 (14), 62.4 (3), 51.3 (6), 50.2 (4);
IR (ATR) ν (cm−1) = 3318, 2920, 2851, 2329, 2162, 2078, 2043,
1895, 1819, 1762, 1657, 1608, 1496, 1443, 1418, 1359, 1317, 1245,
1219, 1185, 1150, 1083, 1034, 952, 915, 859, 813, 752, 690, 656;
Anal. Calcd for C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C,
76.26; H, 5.16; N, 5.47; HRMS (ESI) m/z: [M+Na]+ calcd for
C16H13NO2Na, 274.0839; found, 274.0839.
8-Methyl-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2i). Purified by silica gel column chromatography;
White solid; Isolated yield: 105 mg, 84%; Rf (n-pentane/ethyl
o
1
acetate = 40/1) = 0.05; mp 175-177 C; H NMR (600 MHz,
CDCl3): δ (ppm) 8.07 (dd, J = 7.8, 1.8 Hz, 1H), 8.01 (d, J = 7.8 Hz,
1H), 7.51-7.48 (m, 1H), 7.21-7.18 (m, 1H), 7.11-7.09 (m, 2H), 7.06
(d, J = 8.4 Hz, 1H), 6.03 (t, J = 7.5 Hz, 1H), 3.55 (dd, J = 16.5, 8.1
Hz, 1H), 3.44 (dd, J = 16.8, 7.2 Hz, 1H), 2.35 (s, 3H); 13C{1H}
NMR (151 MHz, CDCl3): δ (ppm) 159.0, 156.8, 138.2, 134.3,
134.1, 128.9, 128.4, 127.3, 125.6, 123.4, 120.0, 116.9, 115.2, 89.7,
35.3, 21.4; MS (EI+, 70 eV): m/z (%) = 252.2 (14), 251.1 (86) [M]+,
249.9 (2), 132.2 (7), 130.9 (73), 130.0 (16), 125.6 (2), 121.1 (7),
120.1 (11), 102.9 (7), 93.2 (2), 92.1 (9), 78.2 (3), 77.1 (5), 65.3 (2),
64.3 (3), 63.0 (3); IR (ATR) ν (cm−1) = 3305, 3036, 2958, 2914,
2325, 2164, 2047, 2003, 1928, 1893, 1847, 1733, 1652, 1609, 1491,
1461, 1408, 1367, 1334, 1312, 1249, 1222, 1166, 1150, 1109, 1075,
1029, 948, 930, 897, 868, 818, 783, 697, 658; Anal. Calcd for
C16H13NO2: C, 76.48; H, 5.21; N, 5.57. Found: C, 76.01; H, 5.07;
N, 5.07; HRMS (ESI) m/z: [M+Na]+ calcd for C16H13NO2Na,
274.0839; found, 274.0838.
10-Methyl-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2o). Purified by silica gel column
chromatography; White solid; Isolated yield: 28 mg, 22%; Rf (n-
pentane/ethyl acetate = 30/1) = 0.09; mp 85-86 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.04 (dd, J = 7.8, 1.2 Hz, 1H), 7.49 (t, J =
7.8 Hz, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.11-7.08 (m, 2H), 7.06-7.02
(m, 2H), 6.01 (t, J = 7.8 Hz, 1H), 3.52 (dd, J = 16.2, 7.8 Hz, 1H),
3.45 (dd, J = 16.2, 7.2 Hz, 1H), 2.67 (s, 3H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 158.4, 156.5, 139.2, 134.1, 132.1, 128.7,
128.6, 126.8, 125.1, 123.2, 122.3, 120.6, 116.5, 90.5, 35.9, 23.2;
MS (EI+, 70 eV): m/z (%) = 253.3 (3), 252.3 (18), 251.2 (100) [M]+,
250.2 (2), 132.3 (6), 131.2 (58), 130.2 (31), 121.2 (12), 120.2 (14),
103.3 (5), 102.3 (2), 93.3 (2), 92.3 (9), 78.3 (2), 77.3 (4), 66.1 (2),
65.3 (2), 64.4 (3); IR (ATR) ν (cm−1) = 3859, 3629, 3349, 3045,
2924, 2855, 2676, 2500, 2328, 2197, 2086, 1991, 1937, 1748, 1679,
1603, 1462, 1407, 1308, 1262, 1226, 1186, 1147, 1108, 1060, 1022,
953, 913, 871, 837, 764, 722, 692; Anal. Calcd for C16H13NO2: C,
76.48; H, 5.21; N, 5.57. Found: C, 76.35; H, 5.58; N, 5.41; HRMS
(ESI) m/z: [M+Na]+ calcd for C16H13NO2Na, 274.0839; found,
274.0838.
8-Hydroxy-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2j). Purified by silica gel column chromatography;
White solid; Isolated yield: 39 mg, 31%; Rf (n-pentane/ethyl acetate
= 8/1) = 0.06; mp 260-262 oC; 1H NMR (600 MHz, (CD3)2CO): δ
(ppm) 8.32 (s, 1H), 7.97 (dd, J = 7.8, 1.8 Hz, 1H), 7.90 (d, J = 8.4
Hz, 1H), 7.59-7.56 (m, 1H), 7.24 (t, J = 8.1 Hz, 1H), 7.14 (d, J =
8.4 Hz, 1H), 6.86 (s, 1H), 6.76 (dd, J = 8.4, 2.4 Hz, 1H), 6.16 (t, J
= 7.5 Hz, 1H ), 3.64 (dd, J = 16.8, 7.8 Hz, 1H), 3.37 (dd, J = 16.2,
6.6 Hz, 1H); 13C{1H} NMR (151 MHz, (CD3)2CO): δ (ppm) 157.6,
156.8, 154.4, 134.1, 133.2, 129.2, 127.7, 123.0, 120.0, 116.7,
115.4, 113.9, 112.4, 89.8, 34.8; MS (EI+, 70 eV): m/z (%) = 254.0
(9), 253.0 (48) [M]+, 134.0 (5), 132.9 (55), 122.0 (7), 119.9 (13),
104.9 (10), 103.9 (16), 93.0 (8), 91.9 (29), 78.0 (13), 77.0 (13), 76.0
(5), 65.0 (13), 63.0 (18), 53.1 (5), 52.0 (10), 51.0 (14), 50.0 (7); IR
(ATR) ν (cm−1) = 3204, 2923, 2853, 2324, 2175, 2097, 1991, 1919,
1838, 1736, 1613, 1576, 1499, 1463, 1347, 1261, 1216, 1154, 1109,
1087, 1027, 977, 939, 894, 857, 827, 802, 753, 692, 657; Anal.
Calcd for C15H11NO3: C, 71.14; H, 4.38; N, 5.53. Found: C, 69.92;
H, 4.54; N, 5.21; HRMS (ESI) m/z: [M+Na]+ calcd for
C15H11NO3Na, 276.0631; found, 276.0628.
2,3,6,6a-tetrahydro-1H,12H-benzo[5,6][1,3]oxazino[3,2-
a]cyclopenta[g]indol-12-one (2p). Purified by silica gel column
chromatography; Yellow solid; Isolated yield: 35 mg, 25%; Rf (n-
pentane/ethyl acetate = 20/1) = 0.50; mp 147-148 oC; 1H NMR (600
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MHz, CDCl3): δ (ppm) 8.06 (dd, J = 7.8, 1.2 Hz, 1H), 7.50-7.47
8.19 (d, J = 8.4 Hz, 1H), 8.07 (dd, J = 7.8, 1.8 Hz, 1H), 7.50 (t, J =
1
2
3
4
5
6
7
8
(m, 1H), 7.18 (t, J = 7.5 Hz, 1H), 7.06-7.02 (m, 2H), 6.99 (d, J =
7.8 Hz, 1H), 5.99-5.95 (m, 1H), 3.54-3.51 (m, 3H), 3.44-3.40 (m,
1H), 2.93-2.87 (m, 2H), 2.07-1.98 (m, 2H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 158.4, 156.8, 147.0, 136.8, 134.3, 130.9,
128.7, 125.6, 123.2, 122.7, 120.8, 120.1, 116.6, 90.3, 35.6, 35.2,
33.5, 25.6; MS (EI+, 70 eV): m/z (%) = 278.1 (22), 277.0 (100)
[M]+, 158.0 (12), 157.0 (97), 156.0 (54), 155.0 (4), 153.9 (11),
130.0 (7), 129.0 (15), 128.0 (13), 126.9 (7), 120.9 (15), 119.9 (8),
114.9 (6), 92.9 (3), 91.9 (15), 65.0 (4), 64.0 (6), 63.0 (6); IR (ATR)
ν (cm−1) = 3351, 3068, 3015, 2956, 2897, 2841, 2323, 2161, 2096,
1993, 1962, 1885, 1679, 1610, 1416, 1363, 1328, 1225, 1182, 1148,
1117, 1082, 1039, 974, 946, 861, 814, 756, 725, 701, 682, 661;
Anal. Calcd for C18H15NO2: C, 77.96; H, 5.45; N, 5.05. Found: C,
77.76; H, 5.41; N, 5.02; HRMS (ESI) m/z : [M+Na]+ calcd for
C18H15NO2Na, 300.0995; found, 300.0990.
7.8 Hz, 1H), 7.32-7.28 (m, 2H), 7.16 (t, J = 7.5 Hz, 1H), 7.11 (t, J
= 7.5 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H), 3.65 (d, J = 13.8 Hz, 1H),
3.33 (d, J = 13.8 Hz, 1H), 1.60 (s, 3H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 158.5, 155.1, 140.3, 134.6, 128.4, 128.2, 126.9,
125.0, 124.4, 122.8, 118.6, 117.5, 116.2, 96.7, 43.4, 23.9; MS (EI+,
70 eV): m/z (%) = 252.2 (15), 251.2 (93) [M]+, 250.5 (2), 237.3 (9),
236.2 (73), 135.1 (5), 132.2 (9), 131.0 (100), 130.2 (42), 125.7 (2),
121.2 (9), 120.1 (20), 116.1 (2), 103.2 (4), 102.0 (2), 92.1 (24), 90.3
(12), 89.2 (20), 77.3 (5), 65.3 (3), 64.3 (10), 63.1 (14), 51.0 (3); IR
(ATR) ν (cm−1) = 3858, 3622, 3321, 3055, 2972, 2924, 2702, 2491,
2325, 2238, 2145, 2094, 2062, 1999, 1967, 1929, 1737, 1659, 1603,
1483, 1461, 1401, 1321, 1261, 1229, 1150, 1125, 1075, 1022, 957,
927, 871, 842, 757, 697, 664; Anal. Calcd for C16H13NO2: C, 76.48;
H, 5.21; N, 5.57. Found: C, 76.42; H, 5.30; N, 5.53; HRMS (ESI+)
m/z: [M+Na]+ calcd for C16H13NO2Na, 274.0839; found, 274.0839.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5a-Phenyl-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2q). Purified by silica gel column
chromatography; White solid; Isolated yield: 138 mg, 88%; Rf (n-
pentane/ethyl acetate = 40/1) = 0.10; mp 144-145 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.34 (d, J = 16.2 Hz, 1H), 7.93 (dd, J = 7.8,
1.2 Hz, 1H), 7.41-7.35 (m, 4H), 7.23-7.17 (m, 4H), 7.11 (t, J = 7.5
Hz, 1H), 7.05-7.02 (m, 2H), 4.02 (d, J = 15.6 Hz, 1H), 3.49 (d, J =
15.6 Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3): δ (ppm) 159.5,
155.4, 141.8, 141.5, 134.6, 128.8, 128.8, 128.6, 128.2, 126.1,
125.5, 125.2, 124.7, 123.0, 119.6, 117.5, 115.4, 98.3, 45.9; MS
(EI+, 70 eV): m/z (%) = 314.1 (4), 313.2 (19) [M]+, 287.2 (2), 286.2
(2), 260.2 (2), 244.2 (2), 236.1 (2), 194.2 (16), 193.1 (100), 192.3
(9), 191.2 (3), 190.1 (2), 166.2 (3), 165.1 (14), 164.2 (2), 128.2 (2),
121.3 (3), 120.1 (7), 116.2 (2), 115.1 (3), 114.2 (2), 102.2 (2), 92.1
(16), 90.3 (13), 89.2 (24), 77.3 (4), 76.3 (2), 75.3 (2), 74.2 (2), 65.4
(2), 64.4 (8), 63.3 (10), 51.4 (3), 50.4 (2); IR (ATR) ν (cm−1) =
3320, 3044, 2961, 2922, 2852, 2327, 2188, 2162, 2031, 1902, 1822,
1739, 1661, 1604, 1479, 1458, 1398, 1318, 1261, 1221, 1158, 1110,
1018, 966, 924, 870, 808, 752, 699, 664; Anal. Calcd for
C21H15NO2: C, 80.49; H, 4.83; N, 4.47. Found: C, 80.05; H, 4.80;
N, 4.40; HRMS (ESI) m/z: [M+Na]+ calcd for C21H15NO2Na,
336.0995; found, 336.0993.
Phenyl(2-(p-tolyloxy)indolin-1-yl)methanone (3). Purified by
silica gel column chromatography; Yellow solid; Isolated yield: 25
mg, 15%; Rf (n-pentane/ethyl acetate = 5/1) = 0.19; mp 179-181 oC;
1H NMR (600 MHz, DMSO-d6): δ (ppm) 9.30 (br, 1H), 7.39-7.03
(m, 9H), 6.79 (br, 1H), 6.61-6.57 (m, 2H), 5.60 (br, 1H), 3.73-3.69
(m, 1H), 2.76 (d, J = 16.2 Hz, 1H), 2.05 (s, 3H); 13C{1H} NMR
(151 MHz, DMSO-d6): δ (ppm) 169.4, 151.7, 143.5, 137.4, 131.8,
130.2, 129.3, 128.7, 128.6, 127.5, 127.4, 126.9, 125.8, 125.7,
124.5, 116.9, 115.5, 59.9, 46.1, 20.8; MS (EI+, 70 eV): m/z (%) =
330.4 (9), 329.4 (34) [M]+, 225.3 (10), 224.4 (60), 223.2 (14), 208.3
(34), 207.2 (34), 194.2 (3), 180.2 (4), 118.2 (4), 117.1 (8), 106.1
(8), 105.1 (100), 97.2 (4), 91.1 (7), 85.2 (4), 78.2 (4), 77.2 (52),
71.3 (6), 69.2 (4), 65.2 (5), 57.2 (9), 55.1 (4), 51.1 (6); IR (ATR) ν
(cm−1) = 3307, 3065, 3027, 2921, 2854, 2729, 2319, 2167, 2036,
1980, 1943, 1903, 1737, 1625, 1590, 1506, 1472, 1394, 1330, 1266,
1215, 1179, 1157,1104, 1068, 1026, 1001, 972, 935, 876, 820, 786,
749, 696; HRMS (ESI) m/z: [M+Na]+ calcd for C22H19NO2Na,
352.1308; found, 352.1301.
5-Tosyl-5a,6-dihydroindolo[2,1-b]quinazolin-12(5H)-one (2zc).
Purified by silica gel column chromatography; Gray solid; Isolated
yield: 103 mg, 53%; Rf (n-pentane/ethyl acetate = 5/1) = 0.25; mp
o
1
212-213 C; H NMR (600 MHz, CDCl3): δ (ppm) 8.01 (dd, J =
7.8, 1.2 Hz, 1H), 7.78 (dd, J = 7.8, 0.6 Hz, 1H), 7.65 (td, J = 7.8,
1.8 Hz, 1H), 7.55 (d, J = 7.8 Hz, 1H), 7.52-7.49 (m, 1H), 7.24 (d, J
= 7.8 Hz, 1H), 7.12-7.05 (m, 2H), 6.91 (d, J = 7.8 Hz, 2H), 6.80 (d,
J = 8.4 Hz, 2H), 5.84 (dd, J = 10.8, 6.0 Hz, 1H), 4.80 (dd, J = 18.6,
6.0 Hz, 1H), 3.55 (dd, J = 18.3, 11.1 Hz, 1H), 2.22 (s, 3H); 13C{1H}
NMR (151 MHz, CDCl3): δ (ppm) 159.4, 144.7, 140.7, 140.5,
134.5, 132.9, 129.4, 128.9, 128.6, 128.3, 128.1, 127.6, 127.5,
127.0, 124.6, 115.1, 75.5, 30.6, 21.6; MS (EI+, 70 eV): m/z (%) =
392.5 (5), 391.5 (12), 390.5 (48) [M]+, 274.3 (14), 273.4 (12), 236.4
(15), 235.4 (100), 234.3 (34), 233.3 (7), 210.4 (4), 209.4 (12), 208.3
(6), 206.3 (11), 205.3 (12), 180.3 (8), 179.3 (3), 155.2 (5), 132.2
(5), 118.2 (5), 117.2 (48), 92.2 (3), 91.2 (23), 90.1 (9), 89.1 (7),
77.2 (4), 65.2 (8), 63.2 (3); IR (ATR) ν (cm−1) = 3878, 3302, 3050,
2925, 2855, 2651, 2322, 2233, 2167, 2087, 1984, 1913, 1656, 1598,
1485, 1457, 1416, 1352, 1314, 1257, 1227, 1194, 1162, 1111, 1072,
1030, 956, 938, 891, 811, 772, 746, 705, 669; Anal. Calcd for
C22H18N2O3S: C, 67.68; H, 4.65; N, 7.17. Found: C, 67.46; H, 4.53;
N, 7.03; HRMS (ESI) m/z: [M+Na]+ calcd for C22H18N2O3SNa,
413.0930; found, 413.0933.
2,3,4,4a-Tetrahydro-1H,10H-benzo[5,6][1,3]oxazino[2,3-
k]carbazol-10-one (2r). Purified by silica gel column
chromatography; Light yellow solid; Isolated yield: 98 mg, 68%;
o
1
Rf (n-pentane/ethyl acetate = 20/1) = 0.40; mp 111-114 C; H
NMR (600 MHz, CDCl3): δ (ppm) 8.18 (d, J = 7.8 Hz, 1H), 8.08
(dd, J = 7.8, 1.8 Hz, 1H), 7.50-7.48 (m, 1H), 7.31 (t, J = 7.8 Hz,
1H), 7.25 (d, J = 7.2 Hz, 1H), 7.17-7.13 (m, 2H), 7.06 (d, J = 8.4
Hz, 1H), 3.69 (d, J = 6.0 Hz, 1H), 2.33 (dd, J = 14.7, 2.7 Hz, 1H),
2.21 (d, J = 9.6 Hz, 1H), 2.14-2.08 (m, 1H), 1.71-1.68 (m, 1H),
1.46-1.40 (m, 3H), 1.32-1.28 (m, 1H); 13C{1H} NMR (151 MHz,
CDCl3): δ (ppm) 158.3, 155.1, 139.8, 134.4, 131.0, 128.4, 128.2,
124.4, 122.7, 122.7, 118.6, 117.6, 116.6, 97.3, 46.8, 29.8, 22.6,
20.8, 20.5; MS (EI+, 70 eV): m/z (%) = 292.0 (23), 290.9 (100)
[M]+, 290.9 (4), 248.9 (11), 247.8 (67), 234.8 (3), 172.0 (7), 170.9
(62), 169.9 (11), 167.9 (3), 166.9 (3), 143.9 (4), 142.9 (36), 141.9
(3), 130.0 (3), 128.0 (3), 120.9 (4), 119.9 (4), 115.0 (4), 92.0 (6),
77.1 (2), 64.2 (2), 63.2 (2); IR (ATR) ν (cm−1) = 3315, 3051, 2930,
2858, 2657, 2325, 2098, 1993, 1919, 1808, 1655, 1604, 1464, 1405,
1326, 1277, 1232, 1154, 1028, 932, 854, 749, 682; Anal. Calcd for
C19H17NO2: C, 78.33; H, 5.88; N, 4.81. Found: C, 77.26; H, 5.69;
N, 4.67; HRMS (ESI) m/z: [M+Na]+ calcd for C19H17NO2Na,
314.1152; found, 314.1149.
12H-benzo[5,6][1,3]oxazino[3,2-a]indol-12-one (3a).16g Purified
by silica gel column chromatography; Yellow solid; Isolated yield:
10 mg, 43%; Rf (n-pentane/ethyl acetate = 30/1) = 0.50; mp 151-
153 oC; 1H NMR (600 MHz, CDCl3): δ (ppm) 8.58 (d, J = 7.8 Hz,
1H), 8.30 (dd, J = 8.1, 1.5 Hz, 1H), 7.71-7.68 (m, 1H), 7.56 (d, J =
6.6 Hz, 1H), 7.38-7.33 (m, 4H), 6.15 (s, 1H); 13C{1H} NMR (151
MHz, CDCl3): δ (ppm) 156.9, 154.1, 145.9, 135.7, 129.2, 128.3,
5a-Methyl-5a,6-dihydro-12H-benzo[5, 6][1, 3]oxazino[3, 2-
a]indol-12-one (2s). Purified by silica gel column chromatography;
Pink solid; Isolated yield: 102 mg, 81%; Rf (n-pentane/ethyl acetate
= 40/1) = 0.10; mp 89-92 oC; 1H NMR (600 MHz, CDCl3): δ (ppm)
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The Journal of Organic Chemistry
2873. (b) Bandini, M.; Eichholzer, A. Catalytic Functionalization of
128.0, 124.9, 124.2, 122.8, 119.7, 116.6, 116.1, 114.5, 84.4; MS
Indoles in a New Dimension. Angew. Chem. Int. Ed. 2009, 48, 9608.
(2) For selected examples on dearomatization of indole, see: (a) Bera,
S.; Daniliuc, C. G.; Studer, A. Oxidative N-Heterocyclic Carbene
Catalyzed Dearomatization of Indoles to Spirocyclic Indolenines with
a Quaternary Carbon Stereocenter. Angew. Chem. Int. Ed. 2017, 56,
7402. (b) Huang, L.; Cai, Y.; Zhang, H.-J.; Zhang, C.; Dai, L.-X.; You,
S.-L. Highly Diastereo-and Enantioselective Synthesis of Quinuclidine
Derivatives by an Iridium-Catalyzed Intramolecular Allylic
Dearomatization Reaction. CCS Chem. 2019, 1, 106. (c) Cera, G.;
Crispino, P.; Monari, M.; Bandini, M. Stereoselective synthesis of
tetracyclic indolines via gold-catalyzed cascade cyclization reactions.
Chem. Commun. 2011, 47, 7803. (d) Liu, Y.; Xu, W.; Wang, X.
Gold(I)-Catalyzed Tandem Cyclization Approach to Tetracyclic
Indolines. Org. Lett. 2010, 12, 1448. (e) Noey, E. L.; Wang, X.; Houk,
K. N. Selective Gold(I)-Catalyzed Formation of Tetracyclic Indolines:
A Single Transition Structure and Bifurcations Lead to Multiple
Products. J. Org. Chem. 2011, 76, 3477. (f) Schröder, F.; Sharma, U.
K.; Mertens, M.; Devred, F.; Debecker, D. P.; Luque, R.; Van der
Eycken, E. V. Silver-Nanoparticle-Catalyzed Dearomatization of
Indoles toward 3-Spiroindolenines via a 5-exo-dig Spirocyclization.
ACS Catal. 2016, 6, 8156. (g) Wang, Y.; Zheng, C.; You, S.-L. Iridium-
1
2
3
4
5
6
7
8
(EI+, 70 eV): m/z (%) = 236.2 (18), 235.2 (100) [M]+, 234.3 (3),
180.2 (3), 179.1 (19), 178.1 (10), 177.1 (3), 152.1 (6), 151.1 (4),
146.1 (3), 121.1 (7), 120.0 (12), 117.5 (5), 103.9 (3), 103.1 (3), 92.0
(7), 89.1 (4), 76.0 (13), 75.0 (4), 64.1 (4), 63.0 (5), 50.1 (5); IR
(ATR) ν (cm−1) = 3208, 3066, 2925, 2855, 2318, 2164, 1765, 1697,
1599, 1462, 1368, 1294, 1248, 1199, 1154, 1095, 1031, 1001, 956,
904, 871, 822, 747, 683; HRMS (ESI) m/z: [M+H]+ calcd for
C15H10NO2, 236.0706; found, 236.0696.
2,8-Dibromo-5a,6-dihydro-12H-benzo[5,6][1,3]oxazino[3,2-
a]indol-12-one (2zd). Purified by silica gel column
chromatography; White solid; Isolated yield: 59 mg, 70%; Rf (n-
pentane/ethyl acetate = 9/1) = 0.60; mp 157-158 oC; 1H NMR (600
MHz, CDCl3): δ (ppm) 8.17 (d, J = 2.4 Hz, 1H), 7.99 (d, J = 8.4
Hz, 1H), 7.60 (dd, J = 8.7, 2.7 Hz, 1H), 7.42-7.40 (m, 2H), 6.97 (d,
J = 9.0 Hz, 1H), 6.05-6.03 (m, 1H), 3.59 (dd, J = 16.8, 8.4 Hz, 1H),
3.47 (dd, J = 16.8, 6.6 Hz, 1H); 13C{1H} NMR (151 MHz, CDCl3):
δ (ppm) 157.8, 155.8, 139.4, 137.5, 131.6, 131.1, 129.3, 128.2,
121.2, 118.9, 117.1, 116.8, 116.2, 89.8, 34.9; MS (EI+, 70 eV): m/z
(%) = 395.3 (100), 394.4 (10), 393.3 (50) [M]+, 201.2 (8), 200.2
(62), 199.3 (10), 198.2 (67), 197.2 (70), 196.2 (5), 195.2 (71), 172.2
(27), 170.2 (32), 116.3 (31), 89.3 (16), 63.3 (21), 62.2 (4); IR
(ATR) ν (cm−1) = 3861, 3311, 3057, 2924, 2854, 2659, 2322, 2204,
2110, 2026, 1992, 1887, 1756, 1709, 1657, 1598, 1476, 1439, 1401,
1332, 1300, 1245, 1215, 1155, 1067, 1033, 953, 921, 893, 864, 818,
772, 739, 704, 657; Anal. Calcd for C15H9Br2NO2: C, 45.61; H,
2.30; N, 3.55. Found: C, 44.46; H, 2.28; N, 3.34; HRMS (ESI) m/z:
[M+Na]+ calcd for C15H9Br2NO2Na, 415.8892; found, 415.8879.
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Catalyzed
Asymmetric
Allylic
Dearomatization
by
a
Desymmetrization Strategy. Angew. Chem. Int. Ed. 2017, 56, 15093.
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■ ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge at https://
Crystal structure information (CCDC numbers 1977486,
1977487, 1977488, 1977489, 1977490, 1977491, 1977492,
1977493, 1977494 and 1977495), and copies of H and 13C{1H}
1
NMR spectra (PDF)
Crystallographic data for 1i, 2d, 2e, 2i, 2n, 2q, 2r, 2zd, 2zc and
3 (CIF)
■ AUTHOR INFORMATION
Corresponding Author
(4) Zhang, D.; Song, H.; Qin, Y. Total Synthesis of Indoline
Alkaloids: A Cyclopropanation Strategy. Acc. Chem. Res. 2011, 44,
447.
Markus Albrecht
* E-mail: markus.albrecht@oc.rwth-aachen.de;
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Pascal, M.; Scatton, B.; Maffrand, J.-P.; Soubrie, P. Anxiolytic- and
antidepressant-like effects of the non-peptide vasopressin V-1b
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the treatment of stress-related disorders. Proc. Natl. Acad. Sci. USA
2002, 99, 6370. (c) Kitamura, H.; Kato, A.; Esaki, T. AG-041R, a
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N. V.; Tan, J.; Cohen, S. B.; Spencer, K. R.; Gonzalez-Paez, G. E.;
Lakshminarayana, S. B.; Goh, A.; Suwanarusk, R.; Jegla, T.; Schmitt,
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Synthesis and Biological Evaluation of Derivatives of Indoline as
ORCID
Markus Albrecht：0000-0002-3501-1477
Kari Rissanen：0000- 0002-7282-8419
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENT
Jingyu Zhang gratefully acknowledges support by the Chinese
Scholarship Council.
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