FeCl3 catalyzed regioselective C -alkylation of indolylnitroalkenes with amino group substituted arenes

Article abstract of DOI:10.1021/jo4025368

An efficient FeCl₃ catalyzed protocol for the synthesis of amino functionalized indolylnitroalkanes from easily available precursor indolylnitroalkenes and substituted amines has been developed. Regioselective C-alkylation in the presence of fr

Full text of DOI:10.1021/jo4025368

Note
pubs.acs.org/joc
FeCl3 Catalyzed Regioselective C‑Alkylation of Indolylnitroalkenes
with Amino Group Substituted Arenes
Manoj R. Zanwar, Veerababurao Kavala, Sachin D. Gawande, Chun-Wei Kuo, Wen-Chang Huang,*
Ting-Shen Kuo, Hsiu-Ni Huang, Chiu-Hui He, and Ching-Fa Yao*
Department of Chemistry, National Taiwan Normal University, 88, Sec. 4, Tingchow Road, Taipei, Taiwan 116, R.O.C.
S
* Supporting Information
ABSTRACT: An efficient FeCl3 catalyzed protocol for the
synthesis of amino functionalized indolylnitroalkanes from
easily available precursor indolylnitroalkenes and substituted
amines has been developed. Regioselective C-alkylation in the
presence of free amino substituted arenes occurred. The scope
of this methodology shows good functional group tolerance,
and further, this protocol was used to prepare indolylquinoline derivatives.
group substituted arenes to indolylnitroalkenes in the presence
of a catalytic amount of FeCl3.
ndole and its derivatives are important bioactive compounds
1
Iwhich possess biological and pharmacological activity. In
particular, indolylaminoalkane compounds which are derived
from indolylnitroalkane show antimigraine, psychoactive,
neurotransmitter, and antifungal activities (Figure 1).2 Besides
these, indolylnitroalkane derivatives are key intermediates to
many natural products.3
RESULTS AND DISCUSSION
■
We previously reported the arylation of nitroalkenes with
various arenes and heteroarenes using 1 equiv of AlCl3 as the
catalyst at −78 °C to obtain arylated products in quantitative
yield.12 When amino group substituted arenes were used as
substrates in the presence of AlCl3, we obtained a complex
mixture of products. Keeping the importance of amino group
substituted indolylnitroalkanes in mind, we focused our
attention toward screening this reaction with other catalysts.
In this regard, we initially conducted the reaction of 7-
ethylindolylnitroalkene with 2-iodoaniline in the presence of 20
mol % FeCl3 as the catalyst at room temperature. To our
delight, the reaction furnished a 7-ethylindolylnitroalkane
product in 59% isolated yield after 14 h (Scheme 2). The
Owing to the importance of the indolylnitroalkanes, various
synthetic methods have been developed. Among them, C-
alkylation of indoles with nitroalkenes, catalyzed by both Lewis
and Bronsted acids, is one of the most well-established
procedures for achieving both racemic4 and enantioselective
indolylnitroalkanes.5 Recently, Liao and co-workers reported
the rhodium-catalyzed asymmetric addition of arylboronic acids
to indolylnitroalkenes (Scheme 1).6 Moreover, only a few
reports are available for the direct C-alkylation of aryl
substituted nitroalkene with N,N-disubstituted amino-arenes.7
However, the direct C-alkylation of either unsubstituted amino
arenes to indolylnitroalkenes or indoles to 2-aminonitroalkenes
to synthesize the amino substituted indolylnitroalkanes has not
been reported in the literature. The reason for the latter may be
due to the difficulties in the preparation of amino group
substituted nitroalkene from amino benzaldehyde. On the other
hand, in the presence of a nucleophilic amino group there is the
probability of Michael addition rather than C-alkylation.8 The
amino group containing compounds are widely used in industry
for the synthesis of additives, dyes, and agrochemicals,9 and
compounds possessing an amino group can be used for the
synthesis of various heterocycles.10 Hence, the development of
a novel route for the synthesis of an amino group substituted
indolylnitroalkane via direct C-alkylation of indolylnitroalkenes
using efficient processes is an important area of research.
In continuation of our research dealing with the utility of
nitroalkenes in organic synthesis,11 we wish to report, herein, a
new approach for the synthesis of amino functionalized
indolylnitroalkane derivatives via direct C-alkylation of amino
structure of the product was investigated by H and 13C NMR
1
studies and further confirmed by single crystal X-ray analysis
(Figure 2).
After establishing the structure of the product, we focused
our attention on optimization of the reaction by using different
catalysts, solvents, and varying temperature. Initially, to know
the effect of temperature, we conducted the reaction of
indolylnitroalkene and 2-iodoaniline in the presence of FeCl3 in
dichloroethane (DCE) at 60 °C. The reaction under these
conditions provided 62% of the desired product in 6 h (Table
1, entry 2). A slight improvement in the yield of the desired
product was observed, when the reaction was carried out at 80
°C in 4 h (entry 4). Further, an increase in the temperature to
100 °C did not show any noticeable improvement in the
reaction yield. Next, we screened various solvents for this
reaction including CHCl3, acetonitrile, THF, methanol, 1,4-
dioxane, and DMF. The reaction produced a moderate yield of
Received: November 16, 2013
© XXXX American Chemical Society
A
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The Journal of Organic Chemistry
Note
Figure 1. Biologically active indolylaminoalkane derivatives.2
Scheme 1. Synthesis of Indolylnitroalkane
Scheme 2. Reaction of 7-Ethyl Indolylnitroalkene and 2-
Iodoaniline
Table 1. Optimization of Reaction Conditions
sr.
temp
time
(h)
ab
,
no.
solvent
DCE
catalyst
(°C)
result
1
2
3
4
5
6
7
8
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
rt
14
6
59
62
66
68
56
31
26
DCE
60
70
80
80
80
70
80
DCE
5
DCE
4
CHCl3
CH3CN
THF
6
25
10
24
MeOH
mixture of
products
9
1,4-dioxane FeCl3
80
80
80
80
80
80
80
24
13
12
8
42
10
11
12
13
14
15
DMF
DCE
DCE
DCE
DCE
DCE
FeCl3
−
I2
NR
NR
61
InCl3
BF3.OEt2
ZnCl2
25
4
54
38
20
mixture of
products
16
DCE
TiCl4
80
8
21
a
Figure 2. X-ray crystal structure of 1c (ORTEP diagram).
All reactions were performed on a 1 mmol scale with 20 mol %
b
catalyst and 4 mL of solvent unless otherwise noted. Yields refers to
isolated yields of the purified compound.
the desired product, when CHCl3 used as a solvent (entry 5).
Further, when CH3CN, THF, and 1,4-dioxane were used as
solvents, the yields dropped to 31%, 26%, and 42% respectively
with a longer reaction time (entries 6, 7, and 9). However, we
observed a mixture of products in the case of MeOH (entry 8)
while in DMF no conversion to the desired product occurred
(entry 10). Furthermore, we screened the reaction in the
presence of different Lewis acids. When the reaction was
performed in the absence of catalyst, we did not observe any
product (entry 11). The reaction in the presence of I2 and
InCl3 furnished moderate yields of the expected product
(entries 12 and 13). The lower yields of the product were
obtained in the case of BF3·OEt2 and TiCl4 catalysts (entries 14
and 16). Whereas in the presence of ZnCl2, the reaction
produced a mixture of products (entry 15). From the
optimization studies, the ideal reaction conditions were found
to be 20 mol % FeCl3 catalyst, in DCE as solvent at 80 °C.
Having established the optimum reaction conditions, the
scope and generality of this reaction were explored by treating
different indolylnitroalkenes and amino substituted arenes to
generate various substituted indolylnitroalkane products. As
shown in Table 2, when unsubstituted indolylnitroalkene was
treated with 2-iodoaniline, the expected product was formed in
68% yield (Table 2, 1a). Then, the reactions of indolylnitro-
alkene containing methyl and ethyl groups at the seventh
position proceeded well with 2-iodoaniline to give products 1b
and 1c in 64% and 63% yields respectively. Further, the
introduction of an electron withdrawing group at the fifth
B
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Note
a b
,
Table 2. Reaction of Substituted Indolylnitroalkene with Substituted Aniline
a
b
All reactions were performed on a 2 mmol scale. Yields refer to isolated and purified compounds.
position of indolylnitroalkene provided the desired product in
68% yield in 5.5 h (1d). Whereas a strong electron-donating
group at the same position on indolylnitroalkene produced the
expected product in 75% yield in 3.5 h (1e). Moreover, when
N-methylindolylnitroalkene and 2-iodoaniline were used as
substrates in this reaction, the reaction took a longer time to
produce the desired product in 54% yield (1f). On the other
hand, the reactions of 7-methyl-, 7-ethyl-, 5-benzoloxy-, and 5-
methoxyindolylnitroalkenes with 2-bromoaniline provided the
corresponding indolylnitroalkane products (2b, 2c, 2d, and 2e)
in good yields. Interestingly, the reaction also works well when
3-methyl-2-(2-nitrovinyl)-1H-indole is treated with 2-bromoa-
niline to produce the desired product (2f) in 67% yield.
After the successful reaction of various indolylnitroalkenes
with 2-iodo and 2-bromoaniline, we wish to investigate the
scope of this reaction with respect to different aromatic amines
having various electronic properties. The reaction in the
presence of electron withdrawing groups such as −Cl, −Br, and
−COMe provided good yields of the desired products (2a, 3a,
and 4a; Table 3). Electron-donating substitutions at the ortho
position of aniline gave a slightly lower yield of the expected
products compared to the substrate with electron-withdrawing
groups (5a and 6a). When indolylnitroalkene was treated with
3-chloroaniline, the reaction offered the product (7a) in 71%
yield. Whereas in the case of 3-iodoaniline and anthranilic acid,
the yield of the products dropped to 51% and 44% respectively
(8a and 9a). When N-methyl aniline was used as the substrate
the reaction gave a 78% yield of the desired product (10a) in
12 h, while in the case of N,N-dimethylaniline and N-methyl-N-
ethylaniline a longer reaction time was required to afford the
desired products in 83% (33 h) and 66% (44 h) yields
respectively (11a and 12a). When sterically hindered anilines
such as 2,6-dimethylaniline, 2,6-diethylaniline, and 2,6-diiso-
propylaniline were treated with indolylnitroalkene, it undergoes
an efficient reaction that generates the corresponding products
in 77%, 78%, and 84% yields respectively (13a, 14a, and 15a).
After the successful investigations into the scope and
limitations of the C-alkylation of various aniline derivatives
and indolylnitroalkenes, we explored the utility of these newly
synthesized indolylnitroalkanes. It is a well-known fact that
many indolylquinoline derivatives show a broad range of
biological activity such as potent KDR kinase inhibitors,
antimicrobial activity, and male contraceptive activity in adult
rats.13 The syntheses of indolylquinoline derivatives were
accomplished by following the procedure described by Singh
and co-workers.14 The reaction of a 1-(5-(1-(1H-indol-3-yl)-2-
nitroethyl)-2-aminophenyl)ethanone derivative (4a) with
acetophenone in the presence of the InCl3 catalyst furnished
the corresponding indolylquinoline derivative (4af) in 86%
yield in 22 h (Scheme 3) which was confirmed by single-crystal
X-ray analysis
Further, the reaction of 4a and 5,5-dimethylcyclohexane-1,3-
dione was conducted in the presence of the same catalyst to
obtain the corresponding indolylacridone derivative (4ag) in
83% yield.
CONCLUSIONS
■
In summary, we have developed a new and efficient FeCl3
catalyzed regioselective C-alkylation of various indolylnitro-
alkenes with amino substituted arenes under mild reaction
conditions. This procedure provides a novel approach toward
the synthesis of various amino functionalized indolylnitroalkane
derivatives in good to excellent yields. Further, this method-
C
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Note
a b
,
Table 3. Reaction of Indolylnitroalkene with Substituted Aniline
a
b
All reactions were performed on a 2 mmol scale. Yields refer to isolated and purified compounds.
Scheme 3. Synthesis of Indolylquinoline Derivatives
spectra were recorded using ESI or EI+ mode. Melting points were
recorded using an electrothermal capillary melting point apparatus and
are uncorrected.
ology was used to prepare biologically active indolylquinoline
derivatives.
General Procedure for Preparation of Indolylnitroalkane
Derivatives. To a stirred solution of indolylnitroalkene (2 mmol) and
2-iodoaniline (2 mmol) in dichloroethane (6 mL) was added FeCl3
(20 mol %). The reaction mixture was heated at 80 °C, and the
progress of the reaction was monitored by TLC. After completion of
the reaction, the reaction mixture was cooled to room temperature.
Then the reaction mixture was diluted with water and extracted with
ethyl acetate. The organic layer was separated, dried over anhydrous
MgSO4, and concentrated to give the crude product. The resulting
EXPERIMENTAL SECTION
■
General Information. All chemicals were purchased from various
sources and were used directly without further purification. Analytical
thin-layer chromatography was performed using silica gel 60F glass
plates, and silica gel 60 (230−400 mesh) was used in flash
chromatographic separations. NMR spectra were recorded in CDCl3
with tetramethylsilane and chloroform as the internal standards for 1H
NMR (400 MHz) and CDCl3 solvent as the internal standard for 13
C
NMR (100 MHz). Coupling constants were expressed in hertz. HRMS
D
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The Journal of Organic Chemistry
Note
residue was further purified by flash column chromatography (ethyl
acetate/hexane) on silica gel.
1H), 5.04−4.95 (m, 2H), 4.82 (dd, J = 11.9, 8.0 Hz, 1H), 3.80 (brs,
2H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 146.2, 138.1,
137.4, 131.0, 128.9, 126.6, 126.3, 122.4, 119.6, 119.1, 115.0, 112.8,
109.7, 84.5, 79.7, 40.4, 33.0; LRMS (EI) (m/z) (relative intensity) 421
(M+, 53), 361 (100), 233 (16); HRMS (EI) calcd for C17H16O2N3I
(M+): 421.0287, found 421.0292.
Spectral Data. 4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-iodoaniline
(1a). Compound 1a was eluted with 20% EtOAc/Hex as a brown
solid (552 mg, 68%); mp: 82−84 °C; FT-IR (KBr) ν/cm−1 3501,
3425, 1616, 1547, 1493, 1373; 1H NMR (400 MHz, CDCl3) δ (ppm)
8.08 (brs, 1H), 7.58 (s, 1H), 7.44 (d, J = 7.8 Hz, 1H), 7.36 (d, J = 7.8
Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.08 (t, J = 7.4 Hz, 2H), 7.02 (s,
1H), 6.67 (d, J = 8.3 Hz, 1H), 5.05−4.97 (m, 2H), 4.88−4.82 (m,
1H), 4.07 (brs, 2H); 13C NMR (100 MHz, CDCl3) δ 146.4, 138.2,
136.7, 130.9, 129.0, 126.2, 122.9, 121.6, 120.2, 119.1, 115.0, 114.6,
111.6, 84.5, 79.8, 40.5; LRMS (EI) (m/z) (relative intensity) 407 (M+,
86), 361 (42), 347 (100), 299 (27), 233 (26); HRMS (EI) calcd for
C16H14O2N3I (M+): 407.0131, found 407.0135.
2-Iodo-4-(1-(7-methyl-1H-indol-3-yl)-2-nitroethyl)aniline (1b).
Compound 1b was eluted with 20% EtOAc/Hex as a dark brown
solid (540 mg, 64%); mp: 86−88 °C; FT-IR (KBr) ν/cm−1 3400,
3364, 2921, 1612, 1539, 1492, 1373, 779; 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.03 (brs, 1H), 7.58 (d, J = 2.0 Hz, 1H), 7.30−7.28
(m, 1H), 7.08 (dd, J = 8.2, 2.0 Hz, 1H), 7.03−7.00 (m, 3H), 6.66 (d, J
= 8.2 Hz, 1H), 5.04−4.97 (m, 2H), 4.87−4.81 (m, 1H), 2.47 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 146.3, 138.2, 136.3, 131.0, 129.0,
2-Bromo-4-(1-(7-methyl-1H-indol-3-yl)-2-nitroethyl)aniline (2b).
Compound 2b was eluted with 20% EtOAc/Hex as a dark brown
gummy liquid (592 mg, 79%); FT-IR (KBr) ν/cm−1 3413, 3036, 1613,
1
1543, 1495, 1429, 1374, 880; H NMR (400 MHz, CDCl3) δ (ppm)
8.02 (brs, 1H), 7.35 (d, J = 1.8 Hz, 1H), 7.29 (t, J = 8.2 Hz, 1H),
7.07−7.03 (m, 1H), 7.01−7.00 (m, 3H), 6.69 (d, J = 8.2 Hz, 1H),
5.06−4.97 (m, 2H), 4.83 (dd, J = 11.2, 7.4 Hz, 1H), 3.73 (brs, 2H),
2.46 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.5, 136.2, 131.8,
130.5, 127.9, 125.7, 123.3, 121.3, 120.8, 120.3, 116.7, 116.1, 114.8,
109.6, 79.7, 40.7, 16.6; LRMS (EI) (m/z) (relative intensity) 375
(M+ + 2, 48), 373 (M+, 48), 313 (100), 247 (19); HRMS (EI) calcd
for C17H16O2N3Br (M+): 373.0426, found 373.0421.
2-Bromo-4-(1-(7-ethyl-1H-indol-3-yl)-2-nitroethyl)aniline (2c).
Compound 2c was eluted with 20% EtOAc/Hex as a brown solid
(564 mg, 72%); mp: 149−151 °C; FT-IR (KBr) ν/cm−1 3402, 3374,
2962, 1607, 1545, 1496, 1430; 1H NMR (400 MHz, CDCl3) δ (ppm)
8.05 (brs, 1H), 7.36 (d, J = 1.9 Hz, 1H), 7.31−7.29 (m, 1H), 7.08−
7.03 (m, 3H), 6.99 (d, J = 2.3 Hz, 1H), 6.69 (d, J = 8.2 Hz, 1H), 5.06−
4.98 (m, 2H), 4.84 (dd, J = 11.4, 7.6 Hz, 1H), 3.92 (brs, 2H), 2.83 (q,
J = 7.6 Hz, 2H), 1.35 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 143.5, 135.6, 131.9, 130.6, 128.0, 127.0, 126.0, 121.4, 121.2,
120.5, 116.8, 116.2, 115.0, 109.7, 79.8, 40.8, 24.1, 13.9; LRMS (ESI)
(m/z) (relative intensity) 388 (M+ + 1, 15), 329 (24), 327 (27), 181
(61), 143 (100); HRMS (ESI) calcd for C18H19O2N3Br (M+ + H):
388.0661, found 388.0657.
125.8, 123.5, 121.3, 120.8, 120.4, 116.9, 115.2, 115.0, 84.5, 79.8, 40.6,
16.7; LRMS (ESI) (m/z) (relative intensity) 422 (M+ + 1, 16), 292
(35), 263 (100), 102 (29); HRMS (ESI) calcd for C17H17O2N3I (M+
+ H): 422.0366, found 422.0365.
4-(1-(7-Ethyl-1H-indol-3-yl)-2-nitroethyl)-2-iodoaniline (1c).
Compound 1c was eluted with 15% EtOAc/Hex as a dark brown
solid (549 mg, 63%); mp: 154−156 °C; FT-IR (KBr) ν/cm−1 3415,
1
2958, 1631, 1543, 1488, 1370, 788; H NMR (400 MHz, CDCl3) δ
(ppm) 8.06 (brs, 1H), 7.59 (d, J = 2.0 Hz, 1H), 7.32−7.30 (m, 1H),
7.08 (dd, J = 8.3, 2.0 Hz, 1H), 7.06−7.04 (m, 2H), 6.97 (d, J = 2.4 Hz,
1H), 6.65 (d, J = 8.2 Hz, 1H), 5.04−4.97 (m, 2H), 4.87−4.80 (m,
1H), 3.74 (brs, 2H), 2.83 (q, J = 7.6 Hz, 2H), 1.34 (t, J = 7.6 Hz, 3H);
13C NMR (100 MHz, CDCl3) δ 146.3, 138.2, 135.6, 130.9, 129.0,
4-(1-(5-(Benzyloxy)-1H-indol-3-yl)-2-nitroethyl)-2-bromoaniline
(2d). Compound 2d was eluted with 20% EtOAc/Hex as a brown
gummy liquid (728 mg, 78%); FT-IR (KBr) ν/cm−1 3431, 3380, 3028,
1
1615, 1545, 1479, 1373, 794; H NMR (400 MHz, CDCl3) δ (ppm)
7.98 (brs, 1H), 7.44 (d, J = 7.2 Hz, 2H), 7.39−7.26 (m, 4H), 7.24 (t, J
= 9.0 Hz, 1H), 7.04 (d, J = 8.3 Hz, 1H), 6.98−6.92 (m, 3H), 6.70 (d, J
= 8.2 Hz, 1H), 5.03 (s, 2H), 4.99−4.91 (m, 2H), 4.84−4.78 (m, 1H);
13C NMR (100 MHz, CDCl3) δ 153.4, 143.6, 137.6, 131.9, 131.8,
127.0, 126.0, 121.4, 121.3, 120.5, 116.8, 115.0, 115.0, 84.5, 79.8, 40.6,
24.1, 13.9; LRMS (ESI negative) (m/z) (relative intensity) 434 (M+ −
H, 16), 390 (12), 360 (36), 312 (48); HRMS (ESI negative) calcd for
C18H17O2N3I (M − H)−: 434.0366, found 434.0373.
130.3, 128.7, 128.0, 127.9, 127.8, 126.6, 122.4, 116.1, 114.0, 113.6,
112.3, 109.6, 102.8, 79.6, 71.1, 40.6; LRMS (ESI) (m/z) (relative
intensity) 466 (M+ + 1, 8), 297 (12), 236 (34), 181 (100); HRMS
(ESI) calcd for C23H21O3N3Br (M+ + H): 466.0766, found 466.0757.
2-Bromo-4-(1-(5-methoxy-1H-indol-3-yl)-2-nitroethyl)aniline
(2e). Compound 2e was eluted with 20% EtOAc/Hex as a brown
gummy liquid (508 mg, 65%); FT-IR (KBr) ν/cm−1 3429, 2830, 1621,
4-(1-(5-Bromo-1H-indol-3-yl)-2-nitroethyl)-2-iodoaniline (1d).
Compound 1d was eluted with 20% EtOAc/Hex as a dark brown
solid (662 mg, 68%); dark brown solid; mp: 80−82 °C; FT-IR (KBr)
ν/cm−1 3424, 3358, 2917, 1611, 1545, 1490, 1376, 885, 793; 1H NMR
(400 MHz, CDCl3) δ (ppm) 8.21 (brs, 1H), 7.55−7.53 (m, 2H), 7.26
(dd, J = 8.6, 1.8 Hz, 1H), 7.20 (d, J = 8.6 Hz, 1H), 7.07−7.02 (m, 2H),
6.66 (d, J = 8.2 Hz, 1H), 4.98−4.91 (m, 2H), 4.84−4.77 (m, 1H); 13C
NMR (100 MHz, CDCl3) δ 146.5, 138.1, 135.3, 130.3, 128.9, 128.0,
125.9, 122.8, 121.6, 115.0, 114.2, 113.4, 113.1, 84.6, 79.7, 40.2; LRMS
(ESI negative) (m/z) (relative intensity) 483 (M+ − H, 65), 381 (34),
379 (44), 265 (45), 126 (58); HRMS (ESI negative) calcd for
C16H12O2N3BrI (M − H)−: 483.9158, found 483.9149.
1
1585, 1547, 1454, 913; H NMR (400 MHz, CDCl3) δ (ppm) 7.99
(brs, 1H), 7.35 (d, J = 1.8 Hz, 1H), 7.23 (s, 1H), 7.07 (dd, J = 8.2, 1.7
Hz, 1H), 6.99 (s, 1H), 6.87−6.84 (m, 2H), 6.70 (d, J = 8.2 Hz, 1H),
5.00−4.95 (m, 2H), 4.87−4.82 (m, 1H), 4.05 (brs, 2H), 3.79 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 154.4, 143.6, 131.9, 131.8, 130.3,
128.0, 126.7, 122.3, 116.1, 114.2, 113.0, 112.3, 109.7, 101.0, 99.7, 56.1,
40.6; LRMS (EI) (m/z) (relative intensity) 391 (M+ + 2, 49), 389
(M+, 47), 329 (100), 263 (18); HRMS (EI) calcd for C17H16O3N3Br
(M+): 389.0375, found 389.0375.
4-(1-(5-(Benzyloxy)-1H-indol-3-yl)-2-nitroethyl)-2-iodoaniline
(1e). Compound 1e was eluted with 20% EtOAc/Hex as a dark brown
gummy liquid (763 mg, 75%); FT-IR (KBr) ν/cm−1 3419, 3363, 3024,
1613, 1545, 1489, 1372, 1017; 1H NMR (400 MHz, CDCl3) δ (ppm)
7.98 (brs, 1H), 7.57 (d, J = 1.6 Hz, 1H), 7.44 (d, J = 7.3 Hz, 2H), 7.37
(t, J = 7.4 Hz, 2H), 7.31 (t, J = 7.1 Hz, 1H), 7.23 (d, J = 9.6 Hz, 1H),
7.05 (dd, J = 8.2, 1.7 Hz, 1H), 6.97−6.92 (m, 3H), 6.66 (d, J = 8.2 Hz,
1H), 5.04 (s, 2H), 4.97−4.90 (m, 2H), 4.83−4.77 (m, 1H), 4.01 (brs,
2H); 13C NMR (100 MHz, CDCl3) δ 153.6, 146.3, 138.2, 137.7,
132.0, 130.8, 129.0, 128.7, 128.0, 127.8, 126.7, 122.4, 115.1, 114.4,
113.8, 112.3, 102.8, 84.6, 79.7, 71.2, 40.5; LRMS (ESI) (m/z) (relative
intensity) 514 (M+ + 1, 74), 325 (15), 152 (35), 144 (100); HRMS
(ESI) calcd for C23H21O3N3I (M+ + H): 514.0628, found 514.0627.
2-Iodo-4-(1-(1-methyl-1H-indol-3-yl)-2-nitroethyl)aniline (1f).
Compound 1f was eluted with 10% EtOAc/Hex as a brown gummy
liquid (454 mg, 54%); FT-IR (KBr) ν/cm−1 3504, 3425, 1614, 1547,
2-Bromo-4-(1-(3-methyl-1H-indol-2-yl)-2-nitroethyl)aniline (2f).
Compound 2f was eluted with 10% EtOAc/Hex as a brown solid
(505 mg, 67%); mp: 62−64 °C; FT-IR (KBr) ν/cm−1 3439, 1621,
1
1545, 1437, 1307, 760; H NMR (400 MHz, CDCl3) δ (ppm) 7.88
(brs, 1H), 7.37−7.33 (m, 2H), 7.23 (s, 1H), 7.11−7.04 (m, 3H), 6.66
(d, J = 7.9 Hz, 1H), 5.14−5.05 (m, 3H), 4.04 (brs, 2H), 2.38 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 143.2, 135.6, 133.0, 131.5, 130.7,
127.5, 126.9, 121.5, 120.0, 118.7, 116.0, 110.9, 109.6, 108.8, 78.9, 39.6,
12.2; LRMS (EI) (m/z) (relative intensity) 375 (M+ + 2, 31), 373
(M+, 33), 313 (80), 202 (100); HRMS (EI) calcd for C17H16O2N3Br
(M+): 373.0426, found 373.0431.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-bromoaniline (2a). Com-
pound 2a was eluted with 20% EtOAc/Hex as a brown gummy liquid
(592 mg, 82%); FT-IR (KBr) ν/cm−1 3471, 3416, 2921, 1626, 1540,
1493; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.10 (brs, 1H), 7.44 (d, J
1
1494, 1372, 819; H NMR (400 MHz, CDCl3) δ (ppm) 7.59 (d, J =
2.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.29 (d, J = 8.2 Hz, 1H), 7.25−
7.22 (m, 1H), 7.11−7.07 (m, 2H), 6.84 (s, 1H), 6.65 (d, J = 8.2 Hz,
E
dx.doi.org/10.1021/jo4025368 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
= 7.9 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.20 (t, J = 7.2 Hz, 1H),
7.10−7.04 (m, 2H), 7.00 (d, J = 2.1 Hz, 1H), 6.68 (d, J = 8.2 Hz, 1H),
5.07−4.97 (m, 2H), 4.84 (dd, J = 11.8, 8.0 Hz, 1H), 3.51 (brs, 2H);
13C NMR (100 MHz, CDCl3) δ 146.3, 138.1, 136.6, 130.8, 128.9,
126.1, 122.8, 121.7, 120.1, 119.0, 115.0, 114.4, 111.6, 84.5, 79.7, 40.4;
LRMS (EI) (m/z) (relative intensity) 361 (M++2, 26), 359 (M+, 94),
347 (100), 233 (24); HRMS (EI) calcd for C16H14O2N3Br (M+):
359.0269, found 359.0276.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-3-iodoaniline (8a). Compound
8a was eluted with 20% EtOAc/Hex as a brown gummy liquid (414
1
mg, 51%); FT-IR (KBr) ν/cm−1 3439, 3406, 2915, 1623, 1543; H
NMR (400 MHz, CDCl3) δ (ppm) 8.08 (brs, 1H), 7.42 (d, J = 8.0 Hz,
1H), 7.35 (d, J = 8.1 Hz, 1H), 7.24 (d, J = 2.4 Hz, 1H), 7.19 (t, J = 7.6
Hz, 1H), 7.09−7.05 (m, 2H), 6.88 (d, J = 8.4 Hz, 1H), 6.51 (dd, J =
8.4, 2.4 Hz, 1H), 5.46 (dd, J = 9.0, 6.8 Hz, 1H), 4.92−4.79 (m, 2H),
3.64 (brs, 2H); 13C NMR (100 MHz, CDCl3) δ 147.0, 136.7, 130.7,
128.9, 126.5, 126.0, 122.9, 121.8, 120.1, 119.6, 115.7, 114.7, 111.5,
101.5, 78.5, 45.0; LRMS (EI) (m/z) (relative intensity) 407 (M+,
100), 360 (78), 347 (50), 233 (79), 220 (43); HRMS (EI) calcd for
C16H14O2N3I (M+): 407.0131, found 407.0132.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-chloroaniline (3a). Com-
pound 3a was eluted with 20% EtOAc/Hex as a brown gummy liquid
(521 mg, 83%); FT-IR (KBr) ν/cm−1 3479, 3420, 2925, 1612, 1543,
1
1500, 1377; H NMR (400 MHz, CDCl3) δ (ppm) 8.09 (brs, 1H),
5-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-aminobenzoic acid (9a).
Compound 9a was eluted with 30% EtOAc/Hex as a yellow solid
(288 mg, 44%); mp: 217−219 °C; FT-IR (KBr) ν/cm−1 3400, 3374,
1664, 1541, 1418, 1234, 740; 1H NMR (400 MHz, DMSO-d6) δ
(ppm) 10.99 (brs, 1H), 8.47 (brs, 2H), 7.67 (d, J = 2.2 Hz, 1H), 7.41
(t, J = 7.9 Hz, 1H), 7.37−7.28 (m, 3H), 7.05 (t, J = 7.3 Hz, 1H), 6.95−
6.91 (m, 1H), 6.66 (d, J = 8.6 Hz, 1H), 5.23 (dd, J = 12.8, 7.8 Hz, 1H),
5.15 (dd, J = 12.8, 8.7 Hz, 1H), 4.87 (t, J = 8.2 Hz, 1H); 13C NMR
(100 MHz, DMSO-d6) δ 169.3, 150.5, 136.2, 133.4, 130.1, 126.3,
126.0, 122.1, 121.3, 118.6, 118.4, 116.6, 113.6, 111.5, 109.3, 79.5;
LRMS (EI) (m/z) (relative intensity) 325 (M+, 65), 278 (78), 265
(100), 247 (25); HRMS (EI) calcd for C17H15O4N3 (M+): 325.1063,
found 325.1069.
7.43 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.22−7.19 (m, 2H),
7.08 (t, J = 7.5 Hz, 1H), 7.04−7.01 (m, 2H), 6.69 (d, J = 8.2 Hz, 1H),
5.07−4.98 (m, 2H), 4.84 (dd, J = 11.7, 7.9 Hz, 1H), 3.97 (brs, 2H);
13C NMR (100 MHz, CDCl3) δ 142.4, 136.7, 130.1, 128.8, 127.3,
126.2, 122.9, 121.6, 120.1, 119.7, 119.1, 116.3, 114.5, 111.6, 79.8, 40.8;
LRMS (EI) (m/z) (relative intensity) 315 (M+, 46), 268 (67), 255
(100), 233 (17); HRMS (EI) calcd for C16H14O2N3Cl (M+):
315.0775, found 315.0776.
1-(5-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-aminophenyl)ethanone
(4a). Compound 4a was eluted with 20% EtOAc/Hex as a yellow solid
(541 mg, 83%); mp: 157−159 °C; FT-IR (KBr) ν/cm−1 3496, 3429,
1
2913, 1635, 1543, 1418; H NMR (400 MHz, CDCl3) δ (ppm) 8.20
(brs, 1H), 7.67 (d, J = 2.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 1H), 7.36 (d, J
= 8.1 Hz, 1H), 7.23−7.19 (m, 2H), 7.09 (t, J = 7.4 Hz, 1H), 7.00 (d, J
= 2.4 Hz, 1H), 6.59 (d, J = 8.8 Hz, 1H), 6.25 (brs, 2H), 5.11−5.02 (m,
2H), 4.88 (dd, J = 11.4, 8.0 Hz, 1H), 2.52 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 200.7, 149.8, 136.8, 133.8, 131.3, 126.3, 126.2, 123.0,
121.7, 120.2, 119.1, 118.3, 118.2, 114.7, 111.7, 79.8, 41.1, 28.0; LRMS
(ESI) (m/z) (relative intensity) 324 (M+ + 1, 100), 275 (39), 158
(26), 122 (30); HRMS (ESI) calcd for C18H18O3N3 (M+ + H):
324.1348, found 324.1351.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-N-methylaniline (10a). Com-
pound 10a was eluted with 20% EtOAc/Hex as a brown solid (464
mg, 78%); mp: 104−106 °C; FT-IR (KBr) ν/cm−1 3402, 2924, 1647,
1
1547, 1513, 1376, 742; H NMR (400 MHz, CDCl3) δ (ppm) 8.06
(brs, 1H), 7.48−7.45 (m, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.18 (t, J = 7.7
Hz, 1H), 7.13 (d, J = 8.5 Hz, 2H), 7.07 (t, J = 7.5 Hz, 1H), 7.00 (d, J =
2.4 Hz, 1H), 6.56−6.53 (m, 2H), 5.10−4.99 (m, 2H), 4.87 (dd, J =
11.8, 8.0 Hz, 1H), 3.51 (brs, 2H); 13C NMR (100 MHz, CDCl3) δ
148.8, 136.7, 128.8, 127.8, 126.5, 122.7, 121.7, 120.0, 119.3, 115.4,
112.9, 111.5, 80.2, 41.1, 30.9; LRMS (EI) (m/z) (relative intensity)
295 (M+, 46), 235 (100), 124 (8); HRMS (EI) calcd for C17H17O2N3
(M+): 295.1321, found 295.1329.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-methylaniline (5a). Com-
pound 5a was eluted with 25% EtOAc/Hex as a brown solid (428
mg, 72%); mp: 112−114 °C; FT-IR (KBr) ν/cm−1 3429, 3407, 3050,
1
1624, 1544, 1504, 1376; H NMR (400 MHz, CDCl3) δ (ppm) 8.06
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-N,N-dimethylaniline (11a).
Compound 11a was eluted with 15% EtOAc/Hex as a green solid
(516 mg, 83%); mp: 132−134 °C; FT-IR (KBr) ν/cm−1 3412, 3384,
2913, 1642, 1611, 1544, 1520; 1H NMR (400 MHz, CDCl3) δ (ppm)
8.05 (brs, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.2 Hz, 1H),
7.20−7.17 (m, 3H), 7.07 (t, J = 7.5 Hz, 1H), 7.02 (d, J = 2.2 Hz, 1H),
6.68 (d, J = 8.6 Hz, 2H), 5.12−5.00 (m, 2H), 4.88 (dd, J = 12.0, 8.0
Hz, 1H), 2.91 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 150.0, 136.8,
128.6, 127.1, 126.5, 122.7, 121.7, 120.0, 119.3, 115.4, 113.1, 111.5,
80.1, 41.0, 40.8; LRMS (ESI) (m/z) (relative intensity) 310 (M+ + 1,
100); HRMS (ESI) calcd for C18H20O2N3 (M+ + H): 310.1556, found
310.1554.
(brs, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H), 7.19 (t, J
= 7.5 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 6.98 (d, J = 8.0 Hz, 3H), 6.60
(d, J = 7.8 Hz, 1H), 5.08−5.00 (m, 2H), 4.86 (dd, J = 11.7, 7.9 Hz,
1H), 3.41 (brs, 2H), 2.10 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
144.0, 136.7, 130.1, 129.3, 126.4, 126.3, 123.0, 122.7, 121.6, 120.0,
119.2, 115.4, 115.2, 111.5, 80.1, 41.1, 17.6; LRMS (ESI) (m/z)
(relative intensity) 296 (M+ + 1, 44), 199 (17); HRMS (ESI) calcd for
C17H18O2N3 (M+ + H): 296.1399, found 296.1392.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2-methoxyaniline (6a). Com-
pound 6a was eluted with 25% EtOAc/Hex as a brown solid (422
mg, 68%); mp: 128−130 °C; FT-IR (KBr) ν/cm−1 3459, 3372, 2915,
1
1616, 1551, 1518, 1377, 1265, 736; H NMR (400 MHz, CDCl3) δ
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-N-ethyl-N-methylaniline (12a).
Compound 12a was eluted with 15% EtOAc/Hex as a brown solid
(424 mg, 66%); mp: 161−163 °C; FT-IR (KBr) ν/cm−1 3429, 3414,
2958, 1604, 1541, 1508, 1373; 1H NMR (400 MHz, CDCl3) δ (ppm)
8.05 (brs, 1H), 7.49 (d, J = 8.0 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H),
7.21−7.16 (m, 3H), 7.08 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 1.0 Hz, 1H),
6.65 (d, J = 8.6 Hz, 2H), 5.11−5.00 (m, 2H), 4.89 (dd, J = 12.0, 8.0
Hz, 1H), 3.36 (q, J = 7.0 Hz, 2H), 2.88 (s, 3H), 1.10 (t, J = 7.0 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 148.6, 136.7, 128.7, 126.5,
126.4, 122.7, 121.7, 120.0, 119.3, 115.4, 112.7, 111.5, 80.1, 47.0, 41.0,
37.6, 11.5; LRMS (EI) (m/z) (relative intensity) 323 (M+, 52), 263
(100), 261 (17), 131 (8); HRMS (EI) calcd for C19H21O2N3 (M+):
323.1634, found 323.1627.
(ppm) 8.08 (brs, 1H), 7.47 (d, J = 8.0 Hz, 1H), 7.35 (d, J = 7.8 Hz,
1H), 7.19 (t, J = 7.6 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 7.01 (s, 1H),
6.74 (d, J = 9.6 Hz, 2H), 6.64 (d, J = 7.7 Hz, 1H), 5.10−5.00 (m, 2H),
4.88 (dd, J = 11.9, 8.0 Hz, 1H), 3.78 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 147.7, 136.7, 135.7, 129.4, 126.4, 122.8, 121.8, 120.2, 120.1,
119.3, 115.3, 115.2, 111.5, 110.5, 80.1, 55.7, 41.6; LRMS (EI) (m/z)
(relative intensity) 311 (M+, 67), 251 (100), 219 (11), 144 (12);
HRMS (EI) calcd for C17H17O3N3 (M+): 311.1270, found 311.1277.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-3-chloroaniline (7a). Com-
pound 7a was eluted with 25% EtOAc/Hex as a brown solid (448
mg, 71%); mp: 82−84 °C; FT-IR (KBr) ν/cm−1 3467, 3418, 2915,
1
1638, 1547; H NMR (400 MHz, CDCl3) δ (ppm) 8.08 (brs, 1H),
7.43 (d, J = 7.8 Hz, 1H), 7.35 (d, J = 8.2 Hz, 1H), 7.19 (t, J = 7.7 Hz,
1H), 7.11 (d, J = 2.3 Hz, 1H), 7.06 (t, J = 7.4 Hz, 1H), 6.93 (d, J = 8.4
Hz, 1H), 6.75 (d, J = 2.4 Hz, 1H), 6.44 (dd, J = 8.4, 2.4 Hz, 1H), 5.60
(t, J = 7.4 Hz, 1H), 4.99−4.87 (m, 2H), 3.69 (brs, 2H); 13C NMR
(100 MHz, CDCl3) δ 146.9, 136.7, 134.4, 129.8, 126.5, 125.9, 122.8,
121.9, 120.1, 119.3, 116.1, 114.2, 114.1, 111.5, 78.3, 37.5; LRMS (EI)
(m/z) (relative intensity) 315 (M+, 68), 255 (100), 233 (55), 219
(24); HRMS (EI) calcd for C16H14O2N3Cl (M+): 315.0775, found
315.0774.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2,6-dimethylaniline (13a).
Compound 13a was eluted with 20% EtOAc/Hex as a brown solid
(484 mg, 77%); mp: 136−138 °C; FT-IR (KBr) ν/cm−1 3440, 3404,
1
2908, 1628, 1543, 1490, 1373, 740; H NMR (400 MHz, CDCl3) δ
(ppm) 8.08 (brs, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.30 (d, J = 8.0 Hz,
1H), 7.19 (t, J = 7.6 Hz, 1H), 7.08 (t, J = 7.5 Hz, 1H), 6.98 (d, J = 1.8
Hz, 1H), 6.90 (s, 2H), 5.05−4.98 (m, 2H), 4.87 (dd, J = 11.2, 7.3 Hz,
1H), 3.51 (brs, 2H), 2.13 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
F
dx.doi.org/10.1021/jo4025368 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
142.1, 136.6, 128.6, 127.7, 126.4, 122.6, 122.3, 121.6, 119.9, 119.2,
115.3, 111.5, 80.2, 41.1, 17.9; LRMS (EI) (m/z) (relative intensity)
309 (M+, 50), 262 (41), 249 (100); HRMS (EI) calcd for C18H19O2N3
(M+): 309.1477, found 309.1471.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2,6-diethylaniline (14a). Com-
pound 14a was eluted with 15% EtOAc/Hex as a brown gummy liquid
(528 mg, 78%); FT-IR (KBr) ν/cm−1 3402, 2954, 1617, 1547, 1454,
1373, 738; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.05 (brs, 1H), 7.53
(d, J = 7.9 Hz, 1H), 7.33 (d, J = 8.2 Hz, 1H), 7.19 (t, J = 7.8 Hz, 1H),
7.09 (t, J = 7.8 Hz, 1H), 7.00 (d, J = 2.0 Hz, 1H), 6.93 (s, 2H), 5.11−
5.01 (m, 2H), 4.90 (dd, J = 11.9, 7.8 Hz, 1H), 3.69 (brs, 2H), 2.49 (q,
J = 7.5 Hz, 4H), 1.22 (t, J = 7.5 Hz, 6H); 13C NMR (100 MHz,
CDCl3) δ 140.9, 136.7, 128.8, 128.3, 126.5, 125.6, 122.6, 121.8, 119.9,
119.2, 115.4, 111.5, 80.2, 41.4, 24.6, 13.2; LRMS (EI) (m/z) (relative
intensity) 337 (M+, 31), 290 (43), 277 (100), 261 (17), 141 (18);
HRMS (EI) calcd for C20H23O2N3 (M+): 337.1790, found 337.1798.
4-(1-(1H-Indol-3-yl)-2-nitroethyl)-2,6-diisopropylaniline (15a).
Compound 15a was eluted with 15% EtOAc/Hex as a brown
gummy liquid (624 mg, 84%); FT-IR (KBr) ν/cm−1 3403, 2956, 1620,
Financial support for this work by the National Science Council
of the Republic of China (NSC 100-2113-M-003-008-MY3),
National Taiwan Normal University (99T3030-2, 99-D, 100-D-
06), and Instrumentation Centre at National Taiwan Normal
University is gratefully acknowledged.
REFERENCES
■
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1
1546, 1461, 1376; H NMR (400 MHz, CDCl3) δ (ppm) 8.04 (brs,
1H), 7.54 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.1 Hz, 1H), 7.19 (t, J = 7.5
Hz, 1H), 7.09 (t, J = 7.5 Hz, 1H), 6.99−6.98 (m, 3H), 5.12−5.02 (m,
2H), 4.91 (dd, J = 12.0, 7.9 Hz, 1H), 3.76 (brs, 2H), 2.93−2.86 (m,
2H), 1.24−1.20 (m, 12H); 13C NMR (100 MHz, CDCl3) δ 139.6,
136.7, 133.0, 128.9, 126.5, 122.6, 122.4, 122.0, 119.9, 119.3, 115.5,
111.5, 80.2, 41.8, 28.2, 22.6, 22.6; LRMS (EI) (m/z) (relative
intensity) 365 (M+, 35), 305 (100), 276 (7); HRMS (EI) calcd for
C22H27O2N3 (M+): 365.2103, found 365.2104.
6-(1-(1H-Indol-3-yl)-2-nitroethyl)-4-methyl-2-phenylquinoline
(4af). Compound 4af was eluted with 20% EtOAc/Hex as a white
solid (174 mg, 86%); mp: 231−233 °C; FT-IR (KBr) ν/cm−1 3402,
1
2915, 2332, 1627, 1402, 1115, 665; H NMR (400 MHz, CDCl3) δ
(ppm) 8.26 (brs, 1H), 8.16−8.11 (m, 3H), 7.98 (d, J = 1.8 Hz, 1H),
7.17 (s, 1H), 7.66 (dd, J = 8.7, 2.0 Hz, 1H), 7.53−7.43 (m, 4H), 7.36
(d, J = 8.1 Hz, 1H), 7.20 (t, J = 7.6 Hz, 1H), 7.10−7.05 (m, 2H), 5.42
(t, J = 7.9 Hz, 1H), 5.17 (dd, J = 12.7, 7.2 Hz, 1H), 5.08 (dd, J = 12.6,
8.8 Hz, 1H), 2.74 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 157.5,
145.2, 139.7, 137.2, 136.8, 131.1, 129.6, 129.3, 129.0, 127.8, 127.5,
126.3, 123.1, 122.7, 122.1, 120.5, 120.3, 119.0, 114.4, 111.7, 79.6, 42.1,
29.9, 19.3; LRMS (EI) (m/z) (relative intensity) 407 (M+, 36), 360
(100), 347 (71); HRMS (EI) calcd for C26H21O2N3 (M+): 407.1634,
found 407.1637.
7-(1-(1H-Indol-3-yl)-2-nitroethyl)-3,3,9-trimethyl-3,4-dihydro-
acridin-1(2H)-one (4ag). Compound 4ag was eluted with 30%
EtOAc/Hex as a yellow solid (178 mg, 83%); m.p.: 207−209 °C; FT-
IR (KBr) ν/cm−1 2937, 2346, 1686, 1605, 1550, 1373, 1218, 1096,
842, 739; 1H NMR (400 MHz, CDCl3) δ (ppm) 8.37 (brs, 1H), 8.20
(s, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.45 (d, J =
8.0 Hz, 1H), 7.38 (d, J = 8.1 Hz, 1H), 7.22−7.18 (m, 1H), 7.07 (t, J =
7.5 Hz, 2H), 5.41 (t, J = 8.0 Hz, 1H), 5.17 (dd, J = 12.6, 7.0 Hz, 1H),
5.07 (dd, J = 12.5, 8.9 Hz, 1H), 3.17 (s, 2H), 3.04 (s, 3H), 2.65 (s,
2H), 1.12 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 200.6, 161.5,
147.8, 137.6, 136.8, 131.4, 130.1, 127.9, 126.1, 124.7, 124.4, 123.2,
121.9, 120.4, 118.9, 114.1, 111.8, 79.5, 76.9, 55.0, 48.6, 42.1, 32.3, 29.9,
28.5, 16.2; LRMS (EI) (m/z) (relative intensity) 427 (M+, 37), 380
(100), 367 (55); HRMS (EI) calcd for C26H25O3N3 (M+): 427.1896,
found 427.1899.
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ASSOCIATED CONTENT
■
S
* Supporting Information
X-ray crystallographic structures and information; H and 13C
1
NMR spectra. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
(11) (a) Zanwar, M. R.; Raihan, M. J.; Gawande, S. D.; Kavala, V.;
*E-mail: cheyaocf@ntnu.edu.tw.
Janreddy, D.; Kuo, C.-W.; Ambre, R.; Yao, C.-F. J. Org. Chem. 2012,
G
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The Journal of Organic Chemistry
Note
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