Oxygenophilic Lewis Acid Promoted Synthesis of 2-Arylindoles from Anilines and Cyanoepoxides in Alcohol

Article abstract of DOI:10.1021/acs.joc.8b02203

A convenient synthetic method to indoles from anilines and cyanoepoxides was developed under the catalysis of BF₃·OEt₂ or AlCl₃ in alcohols. The reaction involves a tandem reaction of the regiospecific ring-opening of cyanoepoxides with anilines, elimination of cyanide, intramolecular aromatic electrophilic substitution, and water elimination. The Lewis acid generated protic acid is an efficient catalyst. The method features readily accessible starting materials, wide substrate scope, transition-metal-free environment, and regiospecificity in the ring-opening of cyanoepoxides.

Full text of DOI:10.1021/acs.joc.8b02203

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Note
Oxygenophilic Lewis Acid-Promoted Synthesis of 2-
Arylindoles from Anilines and Cyanoepoxides in Alcohol
Chuangchuang Xu, and Jiaxi Xu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02203 • Publication Date (Web): 07 Nov 2018
Downloaded from http://pubs.acs.org on November 8, 2018
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The Journal of Organic Chemistry
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Oxygenophilic Lewis Acid-Promoted Synthesis of 2-Arylindoles from
Anilines and Cyanoepoxides in Alcohol
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Chuangchuang Xu, Jiaxi Xu*
State Key Laboratory of Chemical Resource Engineering, Department of Organic Chemistry, Faculty of Science, Beijing
University of Chemical Technology, Beijing 100029, People’s Republic of China.
Supporting Information
ABSTRACT: A convenient synthetic method to indoles from anilines and cyanoepoxides was developed under the catalysis of BF3
•OEt2 or AlCl3 in alcohols. The reaction involves a tandem reaction of the regionspecific ring-opening of cyanoepoxides with anilines,
elimination of cyanide, intramolecular aromatic electrophilic substitution, and the water elimination. The Lewis acids generated protic
acid is efficient catalyst. The method features readily accessible starting materials, wide substrate scope, transition metal-free, and
regiospecificity in the ring-opening of cyanoepoxides.
Indoles and their derivatives are one of the most widely ex-
isted heterocyclic compounds in nature.1 Because of their
unique biological characteristics and excellent physical proper-
ties they have broad application prospects and great values in
pharmaceuticals and materials sciences.2 Therefore, since in-
dole was discovered and characterized by Baeyer in 1866,3 its
derivatives have attracted considerable attention on developing
safe and effective synthetic methods. Numerous unique syn-
thetic methods have emerged during the past decades, for ex-
ample, Fischer,4 Grandberg,5 Madelung,6 Bischler,7 and other
traditional synthetic methods,8 the recently developed C-H ac-
tivation methods,9 and the functionalization of indoles.10
In 2001, Bonnet-Delpon reported a stepwise synthesis of 3-
trifluoromethylindoles from anilines and 1-ethoxy-1-trifluoro-
methylepoxides through a two-stepped tandem reactions, in-
volving the ring opening of epoxides with anilines and
Scheme 1. Synthesis of indoles from anilines and epoxides.
By summarizing and understanding the synthetic methods of
indoles, the reaction of anilines and epoxides has been consid-
ered as an atom-economic model to synthesize indoles and ex-
plored.11 In 1995, Nishida and co-workers first reported the het-
erogeneous synthesis of indoles from anilines and epoxides
through a vapour phase reaction at more than 300 °C with a
solid catalyst (Scheme 1a).12 Besides, Cho and co-workers
achieved the regioselective synthesis of 2-substituted indoles
from excess anilines (10 equivalents) and epoxides under the
catalysis of ruthenium and equivalent cocatalyst SnCl2 in 2003
(Scheme 1b).13 In 2014, Beller’s group realized the ruthenium-
catalyzed synthesis of indoles from 7-oxabicyclo[4.1.0]heptane
and anilines in the presence of 10 mol% p-toluenesulfonic acid
(Scheme 1b).11 They also realized the regioselective synthesis
of indoles from more sensitive epoxides in one-pot two steps.
the elimination of the ethoxide group first, followed by an in-
tramolecular aromatic electrophilic substitution, finally chlorin-
ation with SOCl2 and base elimination (Scheme 1c).14 Inspired
by this, we designed an oxygenophilic Lewis acid-catalyzed di-
rect conversion of cyanoepoxides and anilines into indoles be-
cause acids can not only promote ring-opening of epoxides and
intramolecular aromatic electrophilic substitution, but also
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elimination of the hydroxyl group, and cyanide is a better leav- best yield was obtained in the reaction under refluxing for 30
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ing group than ethoxide (Scheme 1d). Herein, we present our
synthetic strategy to indoles from anilines and cyanoepoxides
under the catalysis of oxygenophilic BF3•OEt2 or AlCl3 in al-
cohols. The oxirane-2-carbonitriles (cyanoepoxides) were eas-
ily prepared from aldehydes and chloroacetonitrile by the Dar-
zens reaction.
hours (Table 1, entries 16-18). The reaction was also conducted
in the mixed solvent (EtOH:TFE, 3:7) under the catalysis of
AlCl3, but a low yield was obtained (Table 1, entry 19). For the
AlCl3-catalyzed reaction, the optimal reaction conditions are as
following: 1a (1 equiv.), 2a (1.9 equiv.), and AlCl3 (0.1 equiv.)
refluxing in 5 mL of commercial TFE for 30 h (Method B), af-
fording 3aa in 69% isolated yield (Table 1, entry 17).
Table 1. Optimization of the reaction conditionsa
Table 2. Scope of anilinesa
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L.A.b
equiv.
Solvent
EtOH:TFE
3:7
Time
h
Yieldc
%
30
55
64
2a
equiv.
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.7
1.2
1.0
1.0
1.0
1.5
1.9
2.3
1.9
1.9
1.9
1.9
Entry
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0.20 B
0.18 B
0.16 B
0.14 B
0.10 B
0.16 B
0.16 B
0.16 B
0.16 B
0.05 Al
0.10 Al
0.15 Al
0.10 Al
0.10 Al
0.10 Al
0.10 Al
0.10 Al
0.10 Al
0.10 Al
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18
30
36
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3:7
3:7
3:7
3:7
3:7
3:7
3:7
3:7
0:1
0:1
0:1
0:1
0:1
0:1
0:1
0:1
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38
67(64d)
67(64d)
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46
19
35
23
39
74
50
77(51d)
69d
69d
35
0:1
3:7
aReactions were conducted on a 0.5 mmol scale in 5 mL of sol-
vent. bL.A. = Lewis acid, B = BF3•OEt2, Al = AlCl3. cYield de-
aAll reactions were performed on a 0.5 mmol scale, yields are
isolated yields. Method A: 1 (0.5 mmol), 2 (0.75 mmol), and
BF3•OEt2 (0.08 mmol) in 5 mL of 3:7 EtOH/TFE mixed solvent
were refluxed for 20 h. bMethod B: 1 (0.5 mmol), 2 (0.95 mmol),
and AlCl3 (0.05 mmol) in 5 mL of TFE were refluxed for 30 h.
1
termined by H NMR analysis using 1,3,5-trimethoxybenzene
as an internal standard. dIsolated yield. TFE = Trifluoroethanol.
Initially, 3-(4-bromophenyl)oxirane-2-carbonitrile (1a) and
aniline (2a) were employed as the model substrates to optimize
reaction conditions. Detailed optimizations on different Lewis
acids, solvents, and reaction time, equivalents of substrates and
acids are summarized in Table S1 and Table S2 in SI. Detailed
optimizations under the catalysis of efficient Lewis acids
BF3•OEt2 and AlCl3 are present in Table 1. To our delight, 1a
(0.5 mmol) and 2a (1.5 mmol) were treated with BF3•OEt2 (0.20
equiv.) in refluxing EtOH and TFE (3:7, v/v) for 11 h, affording
the desired 2-(4-bromophenyl)-1H-indole (3aa) in 30% yield
(Table 1, entry 1). Evaluation on the equivalent of BF3•OEt2 in-
dicated that 0.16 equivalents of BF3•OEt2 was good choice (Ta-
ble 1, entries 1-5). When the reaction time was extended to 15
and 20 hours, the yield was further increased to 67% NMR yield
and 64% isolated yield (Table 1, entries 6 and 7). Both increase
and decrease of the amount of BF3•OEt2 resulted in loss of the
yield (Table 1, entries 8 and 9). Thus, the optimal reaction con-
ditions under the catalysis of BF3 were identified as: 1 (1 equiv.),
2 (1.5 equiv.), and BF3•OEt2 (0.16 equiv.) in 5 mL of 3:7
EtOH/TFE refluxing for 20 h (Method A)(Table 1, entry 7). The
reaction conditions under the catalysis of AlCl3 were also fur-
ther optomized (Table 1, entries 10-19). Optimization on the
amount of AlCl3 revealed that 0.10 euivalent of AlCl3 was the
best case (Table 1, entries 10-12), while screening the amount
of aniline showed that 1.9 equivalents of aniline was the best
choice (Table 1, entries 13-15). For different reaction times, the
With the optimized conditions in hand, the scope and gener-
ality of the reaction were investigated. Reactions of different
anilines with 3-(4-bromophenyl)-oxirane-2-carbonitrile (1a)
were firstly investigated (Table 2): p, m, o-toluidines (2b-d)
gave the corresponding products 3ab, 3ac, and 3ad in the yields
of 97%, 89%, and 48%, respectively. The yield of the corre-
sponding indoles decreases along with the distance decrease be-
tween the methyl and amino groups on the phenyl ring, indicat-
ing that the steric hindrance around the nitrogen atom of ani-
lines greatly impacted on the reaction. And it was verified that
m-toluidine (2c) only gave 6-methyindole 3ac. For other 4-sub-
stituted anilines 2e-i, anilines 2e-i with electron-donating
groups are well suitable to the reaction and gave 3ae-3ai in 66-
96% yields. Moreover, the steric hindrance of para-substituents
has no obvious effect on the reaction, ethyl, i-Pr, and t-Bu p-
substituted anilines 2g-i provided 3ag-3ai in 96%, 84%, and 90%
yields, respectively. Next, multisubstituted anilines 2j-m were
also investigated, both 3,5-dimethylaniline (2j) and 2,4-dime-
thylaniline (2k) were good substrates, giving rise to 3aj and 3ak
in 95% and 69% yields. While 3,4,5-trimethoxyaniline (2l) and
3,5-dimethoxyaniline (2m) gave 33% yield of 3al and 58%
yield of 3am, respectively, possibly due to the steric hindrance
and the interaction between the oxygen-containing group and
BF3. Additionally, because of the steric hindrance effect 1-
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Additionally, 3-phenyl, 3-(3-bromophenyl), and 3-(2-bromo-
naphthylamine (2n) and 2-naphthylamine (2o) gave 3an and
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3ao in 52% and 19% yields, respectively. Finally, different N-
substituted anilines 2p-s were evaluated as well. N-Methyl, N-
propyl, and N-isopropylanilines (2p-r) were also suitable to the
reaction, yielding 3ap-3ar in 52%, 64%, and 25% yields, re-
spectively. The yields further demonstrate that the steric hin-
drance around the nitrogen atom of anilines impacts on the re-
action. Besides, tetrahydroquinoline (2s) also worked well,
yielding 3as in 40% yield. And N-(4-aminophenyl)acetamide
(2t) gave 3at in 74% yield. As expected, electron-poor 4-bro-
moaniline (2u) generated 3au only in 15% yield.
phenyl)oxirane-2-carbonitriles (1b, 1f, and 1g) also produced
3bb, 3fb, and 3gb in 68%, 82%, and 57% yields, respectively,
similar to those in Method A. Naphthalene-1-yl and naphtha-
lene-2-yloxiranes (1i and 1j) gave 3ib and 3jb in higher yields
of 61% and 76%, respectively, compared with those in Method
A. Similarly, 3-(4-bromophenyl)-2-methyloxirane-2-carboni-
trile (1k) gave 3kb in a higher yield of 65% as well. Finally, the
long-chain n-butyl and phenethyl 3-alkyloxiranes (1l and 1m)
gave rise to 3lb and 3mb in similar yields of 30% and 29% (Ta-
ble 3).
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Reactions of different 3-substitued oxirane-2-carbonitriles
1b-m with 2b were investigated (Table 3). Firstly, for 3-ar-
yloxirane-2-carbonitriles 1b-k, epoxides with both electron-
withdrawing and electron-donating groups on the aryl ring were
good substrates, giving 3bb-3hb in moderate to excellent yields
of 55−98%, and epoxides with electron-withdrawing groups
gave better yields. Besides, 2-bromophenylepoxide (1g) gave
3gb in a lower yield of 55% than 3ab owing to the steric hin-
drance. In addition, naphthalene-1-yl and naphthalene-2-
yloxiranes (1i and 1j) worked well and gave 3ib and 3jb in 42%
and 47% yields, respectively. Trisubstituted 3-(4-bromo-
phenyl)-2-methyloxirane-2-carbonitrile (1k) was also compati-
ble, affording 3kb regiospecifically in 65% yield. Finally, the
long-chain n-butyl and phenethyl 3-alkyloxiranes (1l and 1m)
were suitable substrates and gave 3lb and 3mb in 33% and 47%
yields, respectively.
After comparing and analyzing the yields in Methods A and
B, we can summarized that Method B generally gives similar or
higher yields, except for 3-alkyloxiranes. Taking into account
for the reaction time and economy (the consumption of anilines),
method A is ultimately selected as main conditions, and method
B as standby conditions for the cases of lower yields obtained
in method A. Overall, the results show that this reaction has a
wide substrate scope and great advantages for the regiospecific
synthesis of 2-arylindoles.
Scheme 2. Control experiments
Table 3. Scope of epoxidesa
To better understand the reaction mechanism, some control
experiments were taken into account (Scheme 2): 1) Inorganic
protic acid HCl (PhNH2•HCl and concentrated HCl) were at-
tempted as catalysts in the model reaction, 3aa was obtained in
52%-69%. PhNH2 •HCl and Al(Oi-Pr)3 as co-catalysts also
gave 3aa in a slightly lower yield (47%). However, lower yields
of 3aa were obtained when Al(Oi-Pr)3, Al(OH)3, and Et3N•HCl
in TFE and B(OH)3 and B(OMe)3 in EtOH:TFE (3:7) were ap-
plied as catalysts. 2) 3-(4-Bromophenyl)-2-hydroxy-3-(phenyl-
amino)propanenitrile (4), the by-product isolated in the optimi-
zation process, was reacted under the standard reaction condi-
tions (Method A), giving the desired 3aa in 10% yield. How-
ever, the conversion yield was improved to 30% to 45% under
the catalysis of concentrated HClWhen 2-(4-bromophenyl)-2-
(phenylamino)ethan-1-ol was performed under the standard re-
action conditions, no cyclization product was detected. The re-
sults suggest that the cyano group leaves earlier than the hy-
droxy group in the reaction.
Notes a and b are the same as those in Table 2.
The scope and generality were also simply investigated under
Method B conditions. For primary anilines, 3aa and 3ad were
obtained in 69% and 49% yields, respectively, similar to those
in Method A. Interestingly, 2-naphthalenamine (2o) gave 3ao
in 83% yield, a higher yield than that in Method A. Similarly,
the yields of secondary anilines were also obviously improved.
N-Methylaniline (2p) almost gave 3ap quantitatively; N-iso-
propylaniline (2r) and tetrahydroquinoline (2s) gave 3ar and
3as in 50% and 80% yields, respectively, which are double to
those in Method A. These results indicate that AlCl3 is more
powerful than BF3•OEt2 for some certain substrates, such as
secondary anilines, it can overcome partly the adverse effects
of the steric hindrance and the weak nucleophilicity of amines.
However, electron-withdrawing 4-bromoaniline (2u) did not
improve its yield in method B (Table 2).
Based on the control experiments and previously reported
work,15 a plausible mechanism is proposed (Scheme 3): Firstly,
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mesh) with a mixture of petroleum ether (PE, 60 oC90 oC) and
ethyl acetate (EA) as the eluent. All reactions were followed by
thin layer chromatography (TLC) where practical, using silica
gel 60 F254 fluorescent treated silica gel plates, which were vis-
ualized under UV light (254 nm). Commercial grade reagents
and solvents were used without further purification unless oth-
erwise noted.
oxygenophilic Lewis acids react with solvent alcohols to gener-
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ate protic acid, which protonates epoxides 1, forming interme-
diates I. Anilines 2 nucleophilically attack the protonated epoxy
intermediates I regiospecifically on the carbon without the cy-
ano group,16 giving the ring-opening intermediates II. Interme-
diates II further undergo an elimination of HCN, generating in-
termediates III. Next, intermediates III undergo an intramolec-
ular aromatic electrophilic substitution, yielding intermediates
IV, which undergo an acid-promoted elimination of water to
give rise to the final products 3. The elimination may undergo
a favorable solvent-participating transition-state, similar to the
tautomerizations in the Claisen and benzidine rearrangements.17
General procedure for the synthesis of compounds 3.
Method A. A solution of oxirane-2-carbonitrile 1 (0.5 mmol),
aniline 2 (0.75 mmol), and BF3•OEt2 (11.3 µL, 0.08 mmol) in 5
mL of EtOH/TEF (3:7, v/v) mixed solvent was refluxed for 20
h under open air conditions. After cooling to room temperature,
the crude solution was quenched with water (10 mL) and ex-
tracted with ethyl acetate (2 × 10 mL). The combined organic
layer was dried over Na2SO4, filtered, and concentrated in
vacuo. The residue was purified by flash column chromatog-
raphy on silica gel to afford the corresponding indole 3.
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Scheme 3. Proposed mechanism
Method B. A solution of oxirane-2-carbonitrile 1 (0.5 mmol),
aniline 2 (0.95 mmol), and AlCl3 (6.7 mg, 0.05 mmol) in 5 mL
of TEF was refluxed for 30 h under open air conditions. After
cooling to room temperature, the crude solution was quenched
with water (10 mL) and extracted with ethyl acetate (2 × 10 mL).
The combined organic layer was dried over Na2SO4, filtered,
and concentrated in vacuo. The residue was purified by flash
column chromatography on silica gel to afford the correspond-
ing indole 3.
2-(4-Bromophenyl)-1H-indole (3aa).19 Purified by flash col-
umn chromatography (PE/EA 30:1, v/v) on silica gel to give the
desired product as beige solid; Method A: 86 mg, 63%; Method
B: 94 mg, 69%. M.p. 207–209 oC (Lit.19 m.p. 212−213 oC). RF
To demonstrate the synthetic utility of this method, 1-ethyl-
5-methoxy-2-(4-methoxyphenyl)-3-methyl-1H-indole (5),
a
precursor compound to synthesize medicine Zindoxifene, was
obtained in 59% yield under the Method A conditions and 87%
yield under the Method B conditions (Scheme 4). Moreover, a
gram-scale reaction was also conducted under the Method B
conditions, and gave the product 5 in 58% yield.
1
= 0.72, 33% ethyl acetate in petroleum ether. H NMR (400
MHz, CDCl3) δ 8.27 (s, 1H), 7.63 (d, J = 8.0 Hz, 1H), 7.57 (d,
J = 8.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.0 Hz,
1H), 7.23–7.19 (m, 1H), 7.15–7.11 (m, 1H), 6.82 (s, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 136.9, 136.67, 132.2, 131.3,
129.2, 126.6, 122.7, 121.5, 120.8, 120.5, 110.9, 100.5.
Scheme 4. The formal synthesis of Zindoxifene using our
method and the gram-scale reaction.
2-(4-Bromophenyl)-5-methyl-1H-indole (3ab).20 Purified by
flash column chromatography (PE/EA 30:1, v/v) on silica gel to
give the desired product as white solid; 139 mg, 97%. M.p. 279–
o
1
280 C. RF = 0.74, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, CDCl3) δ 8.17 (s, 1H), 7.56 (d, J = 8.4 Hz,
2H), 7.51 (d, J = 8.4 Hz, 2H), 7.41 (s, 1H), 7.28 (d, J = 8.0 Hz,
1H), 7.04 (d, J = 8.0 Hz, 1H), 6.74 (s, 1H), 2.45 (s, 3H).13C{1H}
NMR (101 MHz, CDCl3) δ 136.7, 135.3, 132.1, 131.5, 129.7,
129.5, 126.5, 124.4, 121.3, 120.4, 110.6, 100.1, 21.4.
In summary, we developed a novel and convenient method to
synthesis of indoles from anilines and cyanoepoxides under the
catalysis of BF3•OEt2 or AlCl3 in alcohols. The oxygenophilic
Lewis acid-generated protic acid promotes not only the regio-
specific ring-opening of epoxides, but also intramolecular aro-
matic electrophilic substitution and elimination of water. The
current method features advantages of readily accessible start-
ing materials, wide substrate scope, transition metal-free, and
regiospecific synthesis of substituted indoles.
2-(4-Bromophenyl)-6-methyl-1H-indole (3ac). Purified by
flash column chromatography (PE/EA 30:1, v/v) on silica gel to
give the desired product as beige solid; 127 mg, 89%. M.p. 241–
o
1
243 C. RF = 0.59, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, CDCl3) δ 8.14 (s, 1H), 7.56–7.48 (m, 5H),
7.18 (s, 1H), 6.96 (dd, J = 8.0, 0.8 Hz, 1H), 6.77 (dd, J = 2.0,
0.8 Hz, 1H), 2.47 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
137.4, 136.0, 132.7, 132.1, 131.5, 127.0, 126.4, 122.3, 121.2,
120.4, 110.9, 100.4, 21.8. IR (KBr): ν 744, 780, 811, 1005, 1072,
1113, 1231, 1313, 1349, 1412, 1448, 1481, 1529, 1643, 2850,
2920, 3442 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C15H13BrN+ 286.0226; Found 286.0226.
EXPERIMENTAL SECTION
General Information. Melting points were measured on a
1
melting point apparatus and are uncorrected. H, 13C, and 19F
NMR spectra were recorded on a 400 MHz NMR spectrometer.
Chemical shifts are reported in ppm and referenced to tetrame-
thylsilane (TMS) or residual solvent peaks as internal standards
1
(for CDCl3, tetramethylsilane 0 ppm for H and CDCl3 77.00
ppm for 13C; for DMSO-d6, 2.50 ppm for 1H and 39.50 ppm for
13C). IR spectra (KBr pellets, v [cm-1]) were taken on a FT-IR
spectrometer. The high resolution mass spectra were obtained
under ESI ionization using an LC/MSD TOF mass spectrometer.
Column chromatography was carried out on silica gel (200300
2-(4-Bromophenyl)-7-methyl-1H-indole (3ad). Purified by
flash column chromatography (PE/EA 30:1, v/v) on silica gel to
give the desired product as beige solid; Method A: 68 mg, 48%;
Method B: 70 mg, 49%. M.p. 132–134 oC. RF = 0.62, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 8.10
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The Journal of Organic Chemistry
(d, J = 1.6 Hz, 1H), 1.39 (s, 9H). 13C{1H} NMR (101 MHz,
(s, 1H), 7.56–7.51 (m, 4H), 7.47 (d, J = 8.0 Hz, 1H), 7.07–7.00
(m, 2H), 6.81 (d, J = 2.4 Hz, 1H), 2.53 (s, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 136.5, 136.4, 132.1, 131.4, 128.7, 126.6,
123.3, 121.4, 120.7, 120.1, 118.5, 101.1, 16.7. IR (KBr): ν 743,
799, 826, 1003, 1256, 1304, 1417, 1426, 1479, 1536, 1592,
2913, 2968, 3050, 3446 cm-1. HRMS (ESI-TOF) m/z: [M + H]+
Calcd. for C15H13BrN+ 286.0226; Found 286.0227.
2-(4-Bromophenyl)-5-methoxy-1H-indole (3ae).21 Purified
by flash column chromatography (PE/EA 30:1, v/v) on silica gel
to give the desired product as off-white solid; 116 mg, 77%.
M.p. 214–215 oC (Lit.21 m.p. 201−202 oC). RF = 0.57, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 8.16
(s, 1H), 7.56–7.54 (m, 2H), 7.50–7.48 (m, 2H), 7.27 (d, J = 8.8
Hz, 1H), 7.07 (d, J = 2.4 Hz, 1H), 6.87 (dd, J = 8.8, 2.4 Hz, 1H),
6.74 (d, J = 1.2 Hz, 1H), 3.86 (s, 3H).13C{1H} NMR (101 MHz,
CDCl3) δ 154.7, 137.4, 132.2, 131.4, 129.7, 126.5, 121.4, 113.1,
111.7, 102.3, 100.4, 55.8.
CDCl3) δ 143.4, 136.8, 135.1, 132.1, 131.5, 129.0, 126.5, 121.3,
121.1, 116.6, 110.4, 100.6, 34.6, 31.9. IR (KBr): ν 750, 792,
816, 1074, 1114, 1245, 1300, 1361, 1419, 1456, 2865, 2925,
2964, 3425 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C18H19BrN+ 328.0695; Found 328.0698.
1
2
3
4
5
6
7
8
2-(4-Bromophenyl)-4,6-dimethyl-1H-indole (3aj). Purified
by flash column chromatography (PE/EA 35:1, v/v) on silica gel
to give the desired product as white solid; 142 mg, 95%. M.p.
o
111–113 C. RF = 0.61, 33% ethyl acetate in petroleum ether.
9
1H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 7.54 (d, J = 8.4 Hz,
2H), 7.50 (d, J = 8.4 Hz, 2H), 7.01 (s, 1H), 6.79–6.78 (m, 2H),
2.53 (s, 3H), 2.43 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
137.1, 135.4, 132.9, 132.1, 131.6, 130.0, 127.0, 126.3, 122.6,
121.1, 108.4, 99.0, 21.8, 18.7. IR (KBr): ν 789, 828, 1007, 1071,
1271, 1348, 1375, 1415, 1458, 1481, 1538, 1594, 1619, 2855,
2918, 3008, 3429 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd.
for C16H15BrN+ 300.0382; Found 300.0385.
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-(4-Bromophenyl)-1H-indol-5-ol (3af). Purified by flash
column chromatography (PE/EA 8:1, v/v) on silica gel to give
the desired product as khaki solid; 95 mg, 66%. M.p. 257–258
2-(4-Bromophenyl)-5,7-dimethyl-1H-indole (3ak). Purified
by flash column chromatography (PE/EA 35:1, v/v) on silica gel
to give the desired product as beige solid; 103 mg, 69%. M.p.
1
oC. RF = 0.26, 33% ethyl acetate in petroleum ether. H NMR
o
(400 MHz, DMSO-d6) δ 11.25 (s, 1H), 8.69 (s, 1H), 7.75 (d, J
= 8.4 Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.6 Hz, 1H),
6.84 (s, 1H), 6.75 (s, 1H), 6.64 (d, J = 8.6 Hz, 1H). 13C{1H}
NMR (101 MHz, DMSO-d6) δ 151.0, 136.5, 131.8, 131.7, 129.3,
126.6, 119.9, 112.4, 111.7, 103.8, 98.6. IR (KBr): ν 788, 845,
1210, 1364, 1423, 1452, 1585, 1624, 3252, 3426 cm-1. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd. for C14H11BrNO+ 288.0019;
Found 288.0015.
148–149 C. RF = 0.67, 33% ethyl acetate in petroleum ether.
1H NMR (400 MHz, CDCl3) δ 8.02 (s, 1H), 7.56–7.54 (m, 2H),
7.53–7.50 (m, 2H), 7.24 (s, 1H), 6.85 (s, 1H), 6.73 (d, J = 2.0
Hz, 1H), 2.49 (s, 3H), 2.41 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 136.4, 134.9, 132.1, 131.6, 129.9, 129.0, 126.5, 125.1,
121.2, 119.7, 118.0, 100.7, 21.4, 16.7. IR (KBr): ν 712, 745,
786, 826, 845, 1003, 1035, 1069, 1104, 1167, 1266, 1300, 1459,
1542, 1579, 1593, 2852, 2918, 3452 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C16H15BrN+ 300.0382; Found
300.0384.
2-(4-Bromophenyl)-5-ethyl-1H-indole (3ag). Purified by
flash column chromatography (PE/EA 30:1, v/v) on silica gel to
give the desired product as beige solid; 144 mg, 96%. M.p. 239–
2-(4-Bromophenyl)-4,5,6-trimethoxy-1H-indole (3al). Puri-
fied by flash column chromatography (PE/EA 5:1, v/v) on silica
gel to give the desired product as off-white solid; Method A: 60
mg, 33%; Method B: 46 mg, 25%. M.p. 194–196 oC. RF = 0.26,
o
1
240 C. RF = 0.57, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, CDCl3) δ 8.19 (s, 1H), 7.57–7.55 (m, 2H),
7.52–7.50 (m, 2H), 7.44 (s, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.07
(dd, J = 8.2, 1.2 Hz, 1H), 6.764–6.760 (m, 1H), 2.75 (q, J = 7.6
Hz, 2H), 1.29 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 136.8, 136.5, 135.4, 132.1, 131.5, 129.4, 126.5, 123.4,
121.3, 119.1, 110.7, 100.3, 29.0, 16.4. IR (KBr): ν 789, 810,
828, 1114, 1299, 1418, 1454, 1469, 2850, 2921, 3444 cm-1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C16H15BrN+
300.0382; Found 300.0381.
1
33% ethyl acetate in petroleum ether. H NMR (400 MHz,
CDCl3) δ 8.23 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.46 (d, J = 8.4
Hz, 2H), 6.84 (d, J = 1.6 Hz, 1H), 6.63 (s, 1H), 4.12 (s, 3H),
3.884 (s, 3H), 3.880 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3)
δ 151.7, 145.9, 136.1, 134.9, 134.0, 132.1, 131.3, 126.1, 120.9,
116.6, 98.2, 89.5, 61.5, 60.9, 56.3. IR (KBr): ν 790, 827, 960,
1007, 1109, 1215, 1299, 1466, 1503, 1538, 1627, 2838, 2933,
3333 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C17H17BrNO3+ 362.0386; Found 362.0389.
2-(4-Bromophenyl)-5-isopropyl-1H-indole (3ah). Purified
by flash column chromatography (PE/EA 30:1, v/v) on silica gel
to give the desired product as white solid; 132 mg, 84%. M.p.
2-(4-Bromophenyl)-4,6-dimethoxy-1H-indole (3am). Puri-
fied by flash column chromatography (PE/EA 30:1, v/v) on sil-
ica gel to give the desired product as pale red solid; 96 mg, 58%.
o
196–197 C. RF = 0.60, 33% ethyl acetate in petroleum ether.
1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.53 (d, J = 8.4 Hz,
2H), 7.48 (d, J = 8.4 Hz, 2H), 7.46 (s, 1H), 7.30 (d, J = 8.4 Hz,
1H), 7.10 (dd, J = 8.4, 1.6 Hz, 1H), 6.75 (d, J = 1.6 Hz, 1H),
3.00 (hept, J = 6.8 Hz, 1H), 1.31 (d, J = 6.8 Hz, 6H). 13C{1H}
NMR (101 MHz, CDCl3) δ 141.2, 136.8, 135.5, 132.1, 131.5,
129.3, 126.5, 122.1, 121.3, 117.6, 110.7, 100.4, 34.2, 24.6. IR
(KBr): ν 750, 788, 809, 828, 1004, 1043, 1074, 1240, 1289,
1382, 1420, 1466, 2866, 2923, 3446 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C17H17BrN+ 314.0539; Found
314.0540.
o
M.p. 162–164 C. RF = 0.55, 33% ethyl acetate in petroleum
ether. 1H NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.51 (d, J =
8.4 Hz, 2H), 7.43 (d, J = 8.4 Hz, 2H), 6.83 (d, J = 2.0 Hz, 1H),
6.47 (d, J = 0.8 Hz, 1H), 6.23 (d, J = 2.0 Hz, 1H), 3.93 (s, 3H),
3.84 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 158.1, 153.8,
138.3, 133.9, 132.0, 131.5, 125.9, 120.6, 114.5, 97.8, 92.1,
86.73, 55.7, 55.4. IR (KBr): ν 795, 807, 830, 1008, 1035, 1128,
1148, 1198, 1219, 1278, 1306, 1452, 1464, 1513, 1593, 2839,
2932, 3007, 3348 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd.
for C16H15BrNO2+ 332.0281; Found 332.0280.
2-(4-Bromophenyl)-5-(tert-butyl)-1H-indole (3ai). Purified
by flash column chromatography (PE/EA 30:1, v/v) on silica gel
to give the desired product as white solid; 148 mg, 90%. M.p.
212–214 oC. RF = 0.8, 33% ethyl acetate in petroleum ether. 1H
NMR (400 MHz, CDCl3) δ 8.16 (s, 1H), 7.61 (s, 1H), 7.54 (d, J
= 8.6 Hz, 2H), 7.48 (d, J = 8.6 Hz, 2H), 7.33–7.28 (m, 2H), 6.77
2-(4-Bromophenyl)-1H-benzo[g]indole (3an). Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as brick red solid; 84 mg, 52%. M.p.
o
196–198 C. RF = 0.68, 33% ethyl acetate in petroleum ether.
1H NMR (400 MHz, CDCl3) δ 8.94 (s, 1H), 8.05 (d, J = 8.4 Hz,
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1H), 7.92 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.4 Hz, 1H), 7.60– (PE/DCM 8:1, v/v) on silica gel to give the desired product as
1
2
3
4
5
6
7
8
7.51 (m, 6H), 7.44 (t, J = 8.0 Hz, 1H), 6.94 (d, J = 1.2 Hz, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 135.0, 132.2, 131.6, 131.4,
130.7, 129.1, 126.4, 125.7, 125.3, 124.2, 121.5, 121.5, 121.2,
120.5, 119.3, 102.2. IR (KBr): ν 690, 751, 816, 1005, 1074,
1157, 1212, 1302, 1450, 1479, 1537, 1591, 1629, 2853, 2924,
3048, 3445 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C18H13BrN+ 322.0226; Found 322.0229.
white solid; Method A: 62 mg, 40%; Method B: 125 mg, 80%.
o
M.p. 262–264 C. RF = 0.59, 33% ethyl acetate in petroleum
1
ether. H NMR (400 MHz, DMSO-d6) δ 7.69 (d, J = 8.4 Hz,
2H), 7.59 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 7.4 Hz, 1H), 6.95 (t,
J = 7.4 Hz, 1H), 6.89 (d, J = 7.4 Hz, 1H), 6.59 (s, 1H), 4.21 (t,
J = 6.0 Hz, 2H), 2.95 (t, J = 6.0 Hz, 2H), 2.11 (quint, J = 6.0 Hz,
2H).13C{1H} NMR (101 MHz, DMSO-d6) δ 138.0, 135.0, 131.7,
131.3, 130.1, 125.3, 122.2, 121.0, 119.7, 118.6, 117.5, 100.4,
43.3, 24.2, 22.7. IR (KBr): ν 746, 791, 830, 1006, 1070, 1118,
1262, 1328, 1361, 1377, 1408, 1440, 1451, 1477, 2856, 2925,
2956, 3029, 3051 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd.
for C17H15BrN+ 312.0382; Found 312.0381.
2-(4-Bromophenyl)-3H-benzo[e]indole (3ao). Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as brown solid; Method A: 30 mg, 19%;
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
Method B: 134 mg, 83%. M.p. 168–170 C. RF = 0.62, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
8.58 (s, 1H), 8.24 (d, J = 8.0 Hz, 1H), 7.90 (d, J = 8.0 Hz, 1H),
7.61 (d, J = 8.8 Hz, 1H), 7.60–7.57 (m, 5H), 7.52 (d, J = 8.8 Hz,
1H), 7.43 (t, J = 7.6 Hz, 1H), 7.35 (s, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 134.9, 133.4, 132.2, 131.4, 129.4, 128.7, 128.0,
126.3, 126.0, 124.3, 123.8, 123.7, 122.9, 121.1, 112.4, 99.9. IR
(KBr): ν 747, 772, 800, 825, 1006, 1077, 1154, 1246, 1330,
1373, 1393, 1448, 1461, 1592, 1623, 2853, 2924, 3433 cm-1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C18H13BrN+
322.0226; Found 322.0225.
N-(2-(4-Bromophenyl)-1H-indol-5-yl)acetamide (3at). Pu-
rified by flash column chromatography (DCM/MeOH 150:1,
v/v) on silica gel to give the desired product as beige power; 121
mg, 74%; M.p. 290–291 oC. RF = 0.56, 33% petroleum ether in
ethyl acetate. 1H NMR (400 MHz, DMSO-d6) δ 11.48 (s, 1H),
9.75 (s, 1H), 7.89 (s, 1H), 7.79 (d, J = 8.0 Hz, 2H), 7.64 (d, J =
8.0 Hz, 2H), 7.31 (d, J = 8.4 Hz, 1H), 7.21 (d, J = 8.4 Hz, 1H),
6.90 (s, 1H), 2.04 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6)
δ 167.6, 136.9, 133.9, 132.0, 131.8, 131.5, 128.4, 126.8, 120.2,
115.7, 111.1, 110.3, 99.4, 23.9. IR (KBr): ν 746, 791, 830, 1006,
1070, 1118, 1262, 1328, 1361, 1377, 1408, 1440, 1451, 1540,
1680, 2856, 2925, 2956, 3029, 3051, 3300 cm-1. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd. for C16H14BrN2O+ 329.0284; Found
329.0281.
5-Bromo-2-(4-bromophenyl)-1H-indole (3au).23 Purified by
flash column chromatography (PE/EA 15:1, v/v) on silica gel to
give the desired product as colorless solid; Method A: 27 mg,
15%; Method B: 25 mg, 14%. M.p. 216–218 oC. RF = 0.46, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
8.30 (s, 1H), 7.74 (s, 1H), 7.57 (d, J = 8.2 Hz, 2H), 7.50 (d, J =
8.2 Hz, 2H), 7.30–7.25 (m, 2H), 6.74 (s, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 137.9, 135.5, 132.3, 130.9, 130.8, 126.7,
125.5, 123.2, 122.0, 113.6, 112.3, 100.0.
2-(4-Bromophenyl)-1-methyl-1H-indole (3ap).22 Purified by
flash column chromatography (PE/DCM 8:1, v/v) on silica gel
to give the desired product as white solid; Method A: 75 mg,
52%; Method B: 104 mg, >99%. M.p. 119–120 oC (Lit.22 113–
o
1
114 C). RF = 0.76, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, CDCl3) δ 7.63 (d, J = 7.6 Hz, 1H), 7.60–7.57
(m, 2H), 7.38–7.34 (m, 3H), 7.28–7.24 (m, 1H), 7.16–7.12 (m,
1H), 6.55 (d, J = 0.8 Hz, 1H), 3.72 (s, 3H). 13C{1H} NMR (101
MHz, CDCl3) δ 140.2, 138.5, 131.7, 130.8, 127.8, 122.1, 122.0,
120.6, 120.0, 109.6, 102.0, 31.2.
2-(4-Bromophenyl)-1-propyl-1H-indole (3aq). Purified by
flash column chromatography (PE/DCM 8:1, v/v) on silica gel
to give the desired product as beige solid; Method A: 100 mg,
64%. M.p. 56–58 oC. RF = 0.79, 33% ethyl acetate in petroleum
ether. 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 7.6 Hz, 1H),
7.62–7.59 (m, 2H), 7.41–7.35 (m, 3H), 7.27–7.23 (m, 1H),
7.17–7.13 (m, 1H), 6.53 (s, 1H), 4.11 (t, J = 7.6 Hz, 2H), 1.72
(sext, J = 7.6 Hz, 2H), 0.79 (t, J = 7.6 Hz, 3H). 13C{1H} NMR
(101 MHz, CDCl3) δ 140.1, 137.5, 132.2, 131.7, 130.9, 128.1,
122.2, 121.8, 120.6, 119.9, 110.1, 102.4, 45.6, 23.3, 11.3. IR
(KBr): ν 736, 750, 784, 831, 1009, 1071, 1313, 1346, 1383,
1402, 1459, 1596, 2854, 2873, 2926, 2960 cm-1. HRMS (ESI-
TOF) m/z: [M + H]+ Calcd. for C17H17BrN+ 314.0539; Found
314.0536.
5-Methyl-2-phenyl-1H-indole (3bb).24 Purified by flash col-
umn chromatography (PE/EA 30:1, v/v) on silica gel to give the
desired product as beige solid; Method A: 72 mg, 70%; Method
B: 70 mg, 68%. M.p. 229–230 oC (Lit.24 m.p. 210−212 oC). RF
1
= 0.71, 33% ethyl acetate in petroleum ether. H NMR (400
MHz, DMSO-d6) δ 11.38 (s, 1H), 7.84 (d, J = 7.6 Hz, 2H), 7.44
(t, J = 7.6 Hz, 2H), 7.30–7.27 (m, 3H), 6.92 (d, J = 8.4 Hz, 1H),
6.80 (d, J = 1.2 Hz, 1H), 2.37 (s, 3H).13C{1H} NMR (101 MHz,
DMSO-d6) δ 137.6, 135.5, 132.3, 128.8, 127.7, 127.2, 124.8,
123.2, 119.6, 112.5, 111.1, 98.2, 21.2.
2-(4-Bromophenyl)-1-isopropyl-1H-indole (3ar). Purified
by flash column chromatography (PE/DCM 15:1, v/v) on silica
gel to give the desired product as white solid; Method A: 40 mg,
25%; Method B: 78 mg, 50%. M.p. 183–184 oC. RF = 0.60, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.65–7.58 (m, 4H), 7.34–7.31 (m, 2H), 7.23–7.18 (m, 1H),
7.15–7.11 (m, 1H), 6.46 (s, 1H), 4.63 (hept, J = 7.2 Hz, 1H),
1.61 (d, J = 7.2 Hz, 6H). 13C NMR (101 MHz, CDCl3) δ 140.0,
135.5, 132.6, 131.6, 131.1, 128.9, 122.2, 121.3, 120.9, 119.6,
112.4, 102.5, 48.0, 21.5. IR (KBr): ν 684, 735, 752, 783, 834,
1002, 1013, 1099, 1172, 1306, 1345, 1358, 1369, 1388, 1406,
1460, 1665, 2852, 2872, 2929, 2971, 3046, 3076 cm-1. HRMS
(ESI-TOF) m/z: [M + H]+ Calcd. for C17H17BrN+ 314.0539;
Found 314.0543.
5-Methyl-2-(p-tolyl)-1H-indole (3cb).24 Purified by flash
column chromatography (PE/EA 30:1, v/v) on silica gel to give
the desired product as white solid; 69 mg, 62%. M.p. 240–242
o
oC (Lit.24 m.p. 240 C). RF = 0.78, 33% ethyl acetate in petro-
leum ether. 1H NMR (400 MHz, CDCl3) δ 8.20 (s, 1H), 7.55 (d,
J = 8.0 Hz, 2H), 7.40 (s, 1H), 7.28 (d, J = 8.4 Hz, 1H), 7.25 (d,
J = 8.0 Hz, 2H), 7.01 (d, J = 8.4 Hz, 1H), 6.71 (d, J = 1.6 Hz,
1H), 2.45 (s, 3H), 2.39 (s, 3H).13C{1H} NMR (101 MHz, CDCl3)
δ 138.1, 137.5, 135.0, 129.7, 129.7, 129.6, 129.4, 125.0, 123.7,
120.2, 110.4, 99.0, 21.5, 21.2.
2-(4-Fluorophenyl)-5-methyl-1H-indole (3db).24 Purified
by flash column chromatography (PE/EA 50:1, v/v) on silica gel
to give the desired product as white solid; 96 mg, 85%. M.p.
231–233 oC (Lit.24 m.p. 218−219 oC). RF = 0.71, 33% ethyl ac-
1
2-(4-Bromophenyl)-5,6-dihydro-4H-pyrrolo[3,2,1-i,j]quin-
etate in petroleum ether. H NMR (400 MHz, DMSO-d6) δ
olone (3as). Purified by flash column chromatography
11.37 (s, 1H), 7.88 (d, J = 5.6 Hz, 1H), 7.86 (d, J = 5.6 Hz, 1H),
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7.31–7.27 (m, 4H), 6.92 (d, J = 8.4 Hz, 1H), 6.77 (s, 1H), 2.36
(s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 161.4 (d, JC-F
1394, 1455, 1508, 1588, 1593, 2855, 2924, 3014, 3045, 3398
=
cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C19H16N+
1
2
3
4
5
6
7
245.4 Hz), 136.7, 135.4, 128.97 (d, JC-F = 3.0 Hz), 128.9, 127.8,
126.8 (d, JC-F = 8.1 Hz), 123.2, 119.6, 115.7 (d, JC-F = 21.2 Hz),
110.9, 98.2, 21.2. 19F NMR (376 MHz, DMSO-d6) δ -114.88.
258.1277; Found 258.1279.
5-Methyl-2-(naphthalen-2-yl)-1H-indole (3jb). Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as beige solid; Method A: 61 mg, 47%;
Method B: 98 mg, 76%. M.p. 210–212 oC. RF = 0.68, 33% ethyl
2-(4-Chlorophenyl)-5-methyl-1H-indole (3eb).25 Purified by
flash column chromatography (PE/EA 30:1, v/v) on silica gel to
give the desired product as white solid; 114 mg, 94%. M.p. 263–
1
acetate in petroleum ether. H NMR (400 MHz, DMSO-d6) δ
o
1
266 C. RF = 0.71, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 7.85 (d, J = 8.4
Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.30 (s, 1H), 7.28 (d, J = 8.4
Hz, 1H), 6.93 (dd, J = 8.4, 1.2 Hz, 1H), 6.83 (d, J = 1.2 Hz, 1H),
2.36 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ 136.3,
135.6, 131.6, 131.2, 128.9, 128.8, 127.9, 126.5, 123.5, 119.7,
111.0, 98.8, 21.2.
2-(3-Bromophenyl)-5-methyl-1H-indole (3fb).26 Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as white solid; Method A: 125 mg, 87%;
Method B: 117 mg, 82%. M.p. 196–197 oC (Lit.26 m.p. 189−190
oC). RF = 0.73, 33% ethyl acetate in petroleum ether. 1H NMR
(400 MHz, CDCl3) δ 8.19 (s, 1H), 7.79–7.78 (m, 1H), 7.56 (d,
J = 8.0 Hz, 1H), 7.44–7.42 (m, 2H), 7.31–7.28 (m, 2H), 7.05
(dd, J = 8.0, 1.0 Hz, 1H), 6.76 (d, J = 1.2 Hz, 1H), 2.46 (s, 1H).
13C{1H} NMR (101 MHz, CDCl3) δ 136.2, 135.3, 134.6, 130.5,
130.3, 129.8, 129.3, 128.0, 124.5, 123.5, 123.1, 120.5, 110.6,
100.6, 21.4.
2-(2-Bromophenyl)-5-methyl-1H-indole (3gb).27 Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as beige solid; Method A: 79 mg, 55%;
Method B: 82 mg, 57%. M.p. 125–127 oC. RF = 0.71, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 8.54
(s, 1H), 7.69 (dd, J = 8.0, 1.2 Hz, 1H), 7.61 (dd, J = 7.6, 2.0 Hz,
1H), 7.46 (d, J = 0.8 Hz, 1H), 7.38 (td, J = 7.6, 1.2 Hz, 1H),
7.32 (d, J = 8.4 Hz, 1H), 7.1 (ddd, J = 8.0, 7.6, 1.2 Hz, 1H), 7.07
(dd, J = 8.4, 1.2 Hz, 1H), 6.75 (dd, J = 2.0, 0.8 Hz, 1H), 2.48 (s,
3H). 13C{1H} NMR (101 MHz, CDCl3) δ 136.3, 134.6, 134.0,
133.6, 131.3, 129.4, 129.0, 128.4, 127.6, 124.3, 121.2, 120.3,
110.7, 103.2, 21.5.
11.55 (s, 1H), 8.35 (s, 1H), 8.01 (dd, J = 8.8, 1.2 Hz, 1H), 7.97
(d, J = 8.8 Hz, 1H), 7.93 (d, J = 3.2 Hz, 1H), 7.91 (d, J = 2.8 Hz,
1H), 7.55 (td, J = 7.2 Hz, J = 1.2 Hz, 1H), 7.50 (td, J = 7.2 Hz,
J = 0.8 Hz, 1H), 7.34 (s, 1H), 7.32 (d, J = 8.4 Hz, 1H), 6.96–
6.94 (m, 2H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-
d6) δ 137.5, 135.7, 133.2, 132.2, 129.8, 128.9, 128.3, 127.8,
127.8, 127.6, 126.6, 125.9, 123.7, 123.4, 122.6, 119.7, 111.0,
99.1, 21.2. IR (KBr): ν 749, 794, 823, 854, 1037, 1136, 1236,
1385, 1407, 1453, 1509, 1597, 1644, 2849, 2920, 2953, 3439
cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C19H16N+
258.1277; Found 258.1277.
8
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
2-(4-Bromophenyl)-3,5-dimethyl-1H-indole (3kb). The
product was obtained by recrystallization from EA-PE as pink
solid; Method A: 97 mg, 65%; Method B: 116 mg, 77%. M.p.
o
237–238 C. RF = 0.76, 33% ethyl acetate in petroleum ether.
1H NMR (400 MHz, DMSO-d6) δ 11.06 (s, 1H), 7.69 (d, J = 8.4,
2H), 7.60 (d, J = 8.4, 2H), 7.31 (s, 1H), 7.24 (d, J = 8.2, 1H),
6.94 (d, J = 8.2, 1H), 2.39 (s, 3H), 2.37 (s, 3H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 134.4, 132.5, 132.3, 131.6, 129.5,
129.2, 127.1, 123.5, 119.9, 118.1, 110.8, 107.0, 21.3, 9.8. IR
(KBr): ν 800, 1003, 1245, 1391, 1455, 1475, 1645, 3413 cm-1.
HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for C16H15BrN+
300.0382; Found 300.0378.
2-Butyl-5-methyl-1H-indole (3lb).28 Purified by flash col-
umn chromatography (PE/EA 50:1, v/v) on silica gel to give the
desired product as colorless solid; Method A: 31 mg, 33%;
o
Method B: 28 mg, 30%. M.p. 67–70 C. RF = 0.68, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 7.72
(s, 1H), 7.34 (s, 1H), 7.19 (d, J = 8.2 Hz, 1H), 6.96 (d, J = 8.2
Hz, 1H), 6.18 (d, J = 0.8 Hz, 1H), 2.74 (t, J = 7.8 Hz, 2H), 2.46
(s, 3H), 1.71 (quint, J = 7.8 Hz, 2H), 1.44 (sext, J = 7.8 Hz, 2H),
0.98 (t, J = 7.8 Hz, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
140.1, 134.1, 129.1, 128.7, 122.3, 119.5, 109.9, 99.0, 31.3, 28.0,
22.4, 21.4, 13.8.
4-(5-Methyl-1H-indol-2-yl)benzonitrile (3hb). Purified by
flash column chromatography (PE/EA 25:1, v/v) on silica gel to
give the desired product as beige solid; 114 mg, 98%. M.p. 218–
o
1
220 C. RF = 0.58, 33% ethyl acetate in petroleum ether. H
NMR (400 MHz, DMSO-d6) δ 11.61 (s, 1H), 8.01 (d, J = 8.0,
2H), 7.89 (d, J = 8.0, 2H), 7.34 (s, 1H), 7.31 (d, J = 8.4, 1H),
7.03 (s, 1H), 6.98 (d, J = 8.4, 1H), 2.37 (s, 3H). 13C{1H} NMR
(101 MHz, DMSO-d6) δ 136.6, 136.1, 135.5, 132.8, 128.6,
128.3, 125.2, 124.5, 120.1, 119.0, 111.3, 108.9, 101.1, 21.1. IR
(KBr): ν 792, 838, 1179, 1320, 1425, 1444, 1542, 1604, 2226,
2852, 2920, 3344 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd.
for C16H13N2+ 233.1073; Found 233.1072.
5-Methyl-2-phenethyl-1H-indole (3mb). Purified by flash
column chromatography (PE/DCM 50:1, v/v) on silica gel to
give the desired product as colorless solid; Method A: 55 mg,
47%; Method B: 34 mg, 29%. M.p. 115–118 oC. RF = 0.82, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.63 (s, 1H), 7.33–7.30 (m, 3H), 7.26–7.21 (m, 3H), 7.15 (d, J
= 8.0, 1H), 6.94 (dd, J=8.4, 1.2, 1H), 6.20 (d, J=0.8, 1H), 3.09–
3.01 (m, 4H), 2.43 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ
141.2, 139.1, 134.1, 129.0, 128.8, 128.5, 128.4, 126.2, 122.6,
119.6, 109.9, 99.4, 35.7, 30.2, 21.4. IR (KBr): ν 701, 779, 797,
1056, 1245, 1455, 2929, 2995, 3391 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C17H18N+ 236.1434; Found 236.1438.
5-Methyl-2-(naphthalen-1-yl)-1H-indole (3ib). Purified by
flash column chromatography (PE/EA 50:1, v/v) on silica gel to
give the desired product as beige solid; Method A: 54 mg, 42%;
Method B: 78 mg, 61%. M.p. 106–108 oC. RF = 0.73, 33% ethyl
1
acetate in petroleum ether. H NMR (400 MHz, DMSO-d6) δ
Procedure for the synthesis of 3-(4-bromophenyl)-2-hy-
droxy-3-(phenylamino)propanenitrile (4). A solution of 3-(4-
bromophenyl)oxirane-2-carbonitrile 1a (112 mg, 0.5 mmol),
aniline 2a (69.8 mg, 0.75 mmol) and BF3•OEt2 (17.7 µL, 0.125
mmol) in 5 mL of EtOH was refluxed for 11 h under open air
conditions. After cooling to room temperature, the crude solu-
tion was quenched with water (10 mL) and extracted with ethyl
acetate (2 × 10 mL). The combined organic layer was dried over
11.42 (s, 1H), 8.33–8.31 (m, 1H), 8.03–8.01 (m, 1H), 7.97 (d, J
= 8.0 Hz, 1H), 7.70 (d, J = 6.8 Hz, 1H), 7.63–7.57 (m, 3H), 7.40
(s, 1H), 7.33 (d, J = 8.0 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.64
(s, 1H), 2.41 (s, 3H). 13C{1H} NMR (101 MHz, DMSO-d6) δ
136.4, 135.0, 133.5, 131.0, 130.7, 128.6, 128.4, 128.0, 127.6,
127.1, 126.6, 126.0, 125.5, 125.4, 123.0, 119.5, 111.0, 102.0,
21.2. IR (KBr): ν 686, 776, 792, 1009, 1023, 1110, 1308, 1325,
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o
o
Na2SO4, filtered, and concentrated in vacuo. The residue was
purified by flash column chromatography on silica gel (PE/EA
8:1, v/v) to afford the corresponding 3-(4-bromophenyl)-2-hy-
droxy-3-(phenylamino)propanenitrile (4) 87 mg, 55% yield. RF
= 0.82, 33% ethyl acetate in petroleum ether. 1H NMR (400
MHz, CDCl3) δ 7.41 (d, J = 8.2, 2H), 7.21 (d, J = 8.2, 2H), 7.05
(t, J = 7.8, 2H), 6.69 (t, J = 7.2, 1H), 6.51 (d, J = 8.0, 2H), 4.57
(d, J = 6.0, 1H), 4.54 (d, J = 6.0, 1H), 4.01 (s, 2H). 13C{1H}
NMR (101 MHz, CDCl3) δ 145.3, 135.7, 132.3, 129.4, 129.1,
123.0, 119.5, 117.8, 114.6, 65.1, 60.6. IR (KBr): ν 692, 754,
829, 1010, 1070, 1263, 1315, 1403, 1434, 1504, 1602, 2247
(CN), 2929, 3052, 3388 (br s, OH, NH) cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C15H12BrN2O+ 317.0284; Found
317.0291.
125 C (Lit.29 m.p. 124−126 C). RF = 0.71, 33% ethyl acetate
in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 7.30 (d, J =
8.6, 2H), 7.24 (d, J = 8.8, 1H), 7.03 (d, J = 2.4, 1H), 7.01 (d, J
= 8.6, 2H), 6.88 (dd, J = 8.8, 2.4, 1H), 4.01 (q, J = 7.2, 2H), 3.89
(s, 3H), 3.88 (s, 3H), 2.19 (s, 3H), 1.18 (t, J = 7.2, 3H). 13C{1H}
NMR (101 MHz, CDCl3) δ 159.2, 153.9, 137.8, 131.6, 131.2,
128.9, 124.8, 113.8, 111.4, 110.1, 108.1, 100.8, 56.1, 55.3, 38.6,
15.4, 9.3.
1
2
3
4
5
6
7
8
General procedure for the synthesis of compounds 1. All
oxirane-2-carbonitriles 1 were prepared with the literature re-
ported method.30 A solution of chloroacetonitrile (1.81 g, 24
mmol) or 2-chloropropanenitrile (2.15 g, 24 mmol), KOH (1.35
g, 24 mmol) in 75 mL of THF was added an aldehyde (20 mmol)
in one jet. The reaction mixture was stirred at room temperature
for 24 h. After the mixture solution was concentrated in vacuo,
extracted with ethyl acetate-water, the combined organic phase
was dried over anhydrous Na2SO4. After filtered and concen-
trated in vacuo the residue was purified by flash column chro-
matography on silica gel (PE/EA 30:1, v/v) to afford the corre-
sponding oxirane-2-carbonitrile 1.
cis-3-(4-Bromophenyl)oxirane-2-carbonitrile (1a).31 Color-
less crystals, 1.542 g, 34%. M.p. 105−106 oC (Lit.31 96–97 oC).
RF = 0.50, 33% ethyl acetate in petroleum ether. 1H NMR (400
MHz, CDCl3) δ 7.57 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz,
2H), 4.22 (d, J = 3.6 Hz, 1H), 3.79 (d, J = 3.6 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ 131.9, 130.4, 127.9, 124.0, 114.7,
57.2, 45.0.
9
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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
Procedure for the synthesis of 1-ethyl-5-methoxy-2-(4-
methoxyphenyl)-3-methyl-1H-indole (5).
Method A.
A
solution of 3-(4-methoxyphenyl)-2-
methyloxirane-2-carbonitrile (1n) (94.6 mg, 0.5 mmol), 4-
methoxyaniline (2e) (92.3 mg, 0.75 mmol) and BF3•OEt2 (11.3
µL, 0.08 mmol) in 5 mL of EtOH/TEF (3:7 v/v) mixed solvent
was refluxed for 20 h under open air conditions. After cooling
to room temperature, the crude solution was concentrated in
vacuo and then purified by flash column chromatography on
silica gel using dichloromethane (DCM) as eluent to afford the
crude 5-methoxy-2-(4-methoxyphenyl)-3-methyl-1H-indole
(3ne). 3ne was dissolved in 3 mL of anhydrous DMF. The so-
lution was cooled to 0 oC. 36 mg (0.75 mmol) of NaH (50% oil
suspension) was added. After stirring for 30 min a solution of
65 mg (0.6 mmol) of ethyl bromide in 2 mL of anhydrous DMF
was added. After the reaction mixture was stirred at room tem-
perature for 3 h, the mixture was quenched with water (10 mL)
and extracted with ethyl acetate (3 × 10 mL). The combined
organic layer was washed with brine (3 × 20 mL), and then dried
over Na2SO4. The resulting mixture was concentrated in vacuo
and purified by flash column chromatography on silica gel
(PE/EA 50:1, v/v) to afford the white solid 1-ethyl-5-methoxy-
2-(4-methoxyphenyl)-3-methyl-1H-indole (5) as colorless solid
87 mg, 59% yield.
cis-3-Phenyloxirane-2-carbonitrile (1b).32 Colorless crys-
tals, 0.934 g, 32%. M.p. 60−61 oC (Lit.32 55–56 oC). RF = 0.62,
1
33% ethyl acetate in petroleum ether. H NMR (400 MHz,
CDCl3) δ 7.43 (s, 5H), 4.25 (d, J = 3.6 Hz, 1H), 3.78 (d, J = 3.6
Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 131.3, 129.7,
128.6, 126.3, 115.0, 57.7, 45.1.
cis-3-(p-Tolyl)oxirane-2-carbonitrile (1c).32 Colorless crys-
tals, 509 mg, 16%. M.p. 56−58 oC. RF = 0.68, 33% ethyl acetate
in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J =
8.0 Hz, 2H), 7.24 (d, J = 8.0 Hz, 2H), 4.22 (d, J = 3.8 Hz, 1H),
3.76 (d, J = 3.8 Hz, 1H), 2.38 (s, 3H). 13C{1H} NMR (101 MHz,
CDCl3) δ 139.7, 129.4, 128.3, 126.2, 115.1, 57.7, 45.1, 21.3.
Method B.
A
solution of 3-(4-methoxyphenyl)-2-
methyloxirane-2-carbonitrile (1n) (94.6 mg, 0.5 mmol), 4-
methoxyaniline (2e) (117 mg, 0.95 mmol), and AlCl3 (6.7 mg,
0.05 mmol) in 5 mL of TFE was refluxed for 30 h under open
air conditions. After cooling to room temperature, the crude so-
lution was concentrated in vacuo and then purified by flash col-
umn chromatography on silica gel using dichloromethane
(DCM) as eluent to afford the crude 5-methoxy-2-(4-methoxy-
phenyl)-3-methyl-1H-indole (3ne). 3ne was dissolved in 3 mL
trans-3-(4-Fluorophenyl)oxirane-2-carbonitrile (1d). Col-
o
orless crystals, 1.14 g, 35%. M.p. 62−63 C. RF = 0.78, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.29–7.24 (m, 2H), 7.12–7.06 (m, 2H), 4.28 (d, J = 1.6 Hz, 1H),
3.39 (d, J = 1.8 Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ
163.5 (d, JC-F = 250.5 Hz), 128.5 (d, JC-F = 3.0 Hz), 127.5 (d, JC-
= 9.1 Hz), 116.1 (d, JC-F = 22.2 Hz), 115.7, 57.9, 44.6. 19
F
F
NMR (376 MHz, CDCl3) δ -110.73. IR (KBr): ν 1102, 1120,
1246, 1442, 1518, 1610, 2244, 3033 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C9H7FNO+ 164.0506; Found 164.0510.
cis-3-(4-Chlorophenyl)oxirane-2-carbonitrile (1e).33 Color-
less crystals, 790 mg, 22%. M.p. 87−88 oC (Lit.34 79–81 oC). RF
= 0.6, 33% ethyl acetate in petroleum ether. 1H NMR (400 MHz,
CDCl3) δ 7.42 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 4.23
(d, J = 3.8 Hz, 1H), 3.79 (d, J = 3.8 Hz, 1H). 13C{1H} NMR
(101 MHz, CDCl3) δ 135.8, 129.9, 129.0, 127.7, 114.7, 57.1,
45.0.
o
of anhydrous DMF. The solution was cooled to 0 C. 36 mg
(0.75 mmol) of NaH (50% oil suspension) was added. After stir-
ring for 30 min a solution of 65 mg (0.6 mmol) of ethyl bromide
in 2 mL of anhydrous DMF was added. The reaction was stirred
at room temperature for 3 h. Then the mixture was quenched
with water (10 mL) and extracted with ethyl acetate (3 × 10 mL).
The combined organic layer was washed with brine (3 × 20 mL),
and then dried over Na2SO4. The resulting mixture was concen-
trated in vacuo and purified by flash column chromatography
on silica gel using ethyl acetate/petroleum ether (1/50, v/v) as
eluent to afford white solid 1-ethyl-5-methoxy-2-(4-methoxy-
phenyl)-3-methyl-1H-indole (5) as colorless solid 128 mg, 87%
yield.
trans-3-(3-Bromophenyl)oxirane-2-carbonitrile (1f). Col-
orless crystals, 1.1 g, 25%. M.p. 60−61 oC. RF = 0.53, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 7.56–
7.54 (m, 2H), 7.35–7.26 (m, 2H), 4.21 (s, 1H), 3.78 (d, J = 1.2
Hz, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ 133.7, 132.8,
Gram-scale reaction was conducted on a 10 mmol scales re-
action in 50 mL solvent, affording 1.72 g, 58% yield. M.p. 124–
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The Journal of Organic Chemistry
2.82 (m, 2H), 2.13–2.07 (m, 2H). 13C{1H} NMR (101 MHz,
130.3, 129.5, 124.7, 122.7, 114.5, 56.8, 44.9. IR (KBr): ν 1050,
1
2
3
4
5
6
7
8
1070, 1116, 1187, 1241, 1258, 1433, 1475, 1570, 1599, 2249,
2925, 3030 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C9H7BrNO+ 223.9706; Found 223.9704.
CDCl3) δ 139.8, 128.7, 128.4, 126.5, 115.7, 56.7, 41.9, 31.9,
31.4. IR (KBr): ν 751, 792, 1010, 1029, 1251, 1383, 1421, 1455,
1515, 1603, 2246, 2925, 2953, 3028 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C11H12NO+ 174.0913; Found 174.0922.
cis/trans-3-(2-Bromophenyl)oxirane-2-carbonitrile (1g).
Colorless oil, 3.58 g, 80%. RF = 0.73, 33% ethyl acetate in pe-
troleum ether. cis:trans = 44:56; 1H NMR (400 MHz, CDCl3) δ
7.62–7.58 (m, 1H), 7.42–7.24 (m, 2H), 7.17 (d, J = 7.6 Hz, 1H),
4.56 (d, J = 1.4 Hz, 1H) (trans-isomer), 4.46 (d, J = 3.6 Hz, 1H)
(cis-isomer), 3.86 (d, J = 3.6 Hz, 1H) (cis-isomer), 3.31 (d, J =
1.4 Hz, 1H) (trans-isomer). 13C{1H} NMR (101 MHz, CDCl3)
δ 132.8, 132.7, 132.6, 131.5, 130.9, 130.8, 127.9, 127.7, 127.4,
126.1, 122.7, 122.5, 115.7, 114.6, 58.3, 57.7, 44.5, 44.0. IR
(KBr): ν 752, 800, 1027, 1101, 1160, 1192, 1237, 1442, 1474,
1570, 1593, 2248, 2853, 2924 cm-1. HRMS (ESI-TOF) m/z: [M
+ H]+ Calcd. for C9H7BrNO+ 223.9706; Found 223.9711.
3-(4-Methoxyphenyl)-2-methyloxirane-2-carbonitrile (1n).
colorless oil, 2.21 g, 58%. RF = 0.71, 33% ethyl acetate in pe-
1
troleum ether. H NMR (400 MHz, CDCl3) δ 7.21 (d, J=8.8,
2H), 6.92 (d, J=8.8, 2H), 4.42 (s, 1H), 3.82 (s, 3H), 1.39 (s, 3H).
13C{1H} NMR (101 MHz, CDCl3) δ 160.2, 128.0, 123.1, 119.3,
114.0, 62.8, 55.3, 50.0, 15.1. IR (KBr): ν 776, 812, 1031, 1077,
1112, 1173, 1248, 1384, 1443, 1460, 1514, 1584, 1613, 2241,
2934, 2961 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C11H12NO2+ 190.0863; Found 190.0869.
Synthesis of compound 6.36a 2-(4-Bromophenyl)-2-(phenyl-
amino)ethan-1-ol (6) was prepared on a 10 mmol scale reaction
according to the literature reported method,36b giving the prod-
uct 331 mg, 11% yield. 1H NMR (400 MHz, CDCl3) δ 7.45 (d,
J = 8.4, 2H), 7.24 (d, J = 8.4, 2H), 7.10 (t, J = 7.6, 2H), 6.69 (t,
J = 7.6, 2H), 6.52 (d, J = 7.6, 1H), 4.50 (s, 1H), 4.43 (dd, J =
6.8, 4.0, 1H), 3.90 (dd, J = 11.2, 4.0, 1H), 3.70 (dd, J = 11.2,
6.8, 1H), 1.84 (s, 1H). 13C{1H} NMR (101 MHz, CDCl3) δ146.9,
139.3, 131.9, 129.2, 128.5, 121.4, 118.1, 113.8, 67.1, 59.4.
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cis-3-(4-Cyanophenyl)oxirane-2-carbonitrile (1h).35 Color-
o
less crystals, 578 mg, 17%. M.p. 113−115 C. RF = 0.30, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.74 (d, J = 8.2 Hz, 2H), 7.54 (d, J = 8.2 Hz, 2H), 4.31 (d, J =
3.8 Hz, 1H), 3.86 (d, J = 3.8 Hz, 1H). 13C{1H} NMR (101 MHz,
CDCl3) δ 136.6, 132.5, 127.1, 118.1, 114.3, 113.7, 56.8, 45.0.
cis-3-(Naphthalen-1-yl)oxirane-2-carbonitrile (1i). Color-
less crystals, 312 mg, 8%. M.p. 76−77 oC. RF = 0.63, 33% ethyl
acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ 8.00–
7.98 (m, 1H), 7.96–7.91 (m, 2H), 7.63–7.52 (m, 4H), 4.84 (d, J
= 3.6 Hz, 1H), 3.99 (d, J = 3.6 Hz, 1H). 13C{1H} NMR (101
MHz, CDCl3) δ 133.3, 130.9, 129.8, 129.1, 127.4, 127.0, 126.3,
125.3, 123.7, 121.9, 114.9, 56.1, 44.8. IR (KBr): ν 796, 886,
1028, 1056, 1123, 1160, 1216, 1256, 1459, 1512, 1597, 2248,
2924, 2955 cm-1. HRMS (ESI-TOF) m/z: [M + H]+ Calcd. for
C13H10NO+ 196.0757; Found 176.0754.
cis-3-(Naphthalen-2-yl)oxirane-2-carbonitrile (1j).33 col-
orless crystals, 741 mg, 19%. M.p. 137−139 oC. RF = 0.58, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.93–7.86 (m, 4H), 7.56–7.52 (m, 2H), 7.49 (dd, J = 8.4, 1.6 Hz,
1H), 4.42 (d, J = 3.8 Hz, 1H), 3.86 (d, J = 3.8 Hz, 1H). 13C{1H}
NMR (101 MHz, CDCl3) δ 133.9, 132.9, 128.8, 128.7, 128.1,
127.9, 126.9, 126.7, 126.3, 123.0, 115.0, 57.9, 45.2.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications website at DOI:
Table S1 and Table S2 on optimizations of reaction conditions,
copies of 1H NMR, 13C NMR, and 19F NMR spectra for all isolated
compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
* E-mail: jxxu@mail.buct.edu.cn.
ORCID
Jiaxi Xu: 0000-0002-9039-4933;
Chuangchuang Xu: 0000-0002-7383-2313.
Notes
3-(4-Bromophenyl)-2-methyloxirane-2-carbonitrile (1k).
Colorless crystals, 1.05 g, 22%. M.p. 88−89 oC. RF = 0.60, 33%
ethyl acetate in petroleum ether. 1H NMR (400 MHz, CDCl3) δ
7.55 (d, J = 8.6, 2H), 7.27 (d, J = 8.6, 2H), 3.96 (s, 1H), 1.78 (s,
1H). 13C{1H} NMR (101 MHz, CDCl3) δ 131.8, 131.2, 127.9,
123.7, 116.8, 63.5, 53.4, 20.7. IR (KBr): ν 1010, 1067, 1420,
1451, 1490, 1594, 2244, 2938, 2996 cm-1. HRMS (ESI-TOF)
m/z: [M + H]+ Calcd. for C10H9BrNO+ 237.9862; Found
237.9857.
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the National Natural Science Founda-
tion of China (Nos. 21572017 and 21372025).
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