Efficient synthesis of 3-substituted indoles via a base-free copper-catalysed three-component reaction in water

Article abstract of DOI:10.3184/174751916X14622783380474

The preparation of sixteen 3-substituted indoles in good to excellent yields under environmentally friendly conditions has been achieved via a three-component reaction in water of an indole, an aldehyde and malononitrile (or ethyl 2-cyanoacetate) catalysed by 5 mol% of 2-pyrrolecarbaldiminato-Cu(II).

Full text of DOI:10.3184/174751916X14622783380474

338 RESEARCH PAPER
VOL. 40 JUNE, 338–340
JOURNAL OF CHEMICAL RESEARCH 2016
Efficient synthesis of 3-substituted indoles via a base-free copper-catalysed
three-component reaction in water
a
b
a
Haojie Jiang , Leilei Wang and Jianwei Xie *
a
School of Chemistry and Chemical Engineering, Shihezi University, North 4th Road, Shihezi 832003, P.R China
Biotechnology Center of Shandong Academy of Sciences, Jinan 250014, P.R. China
b
The preparation of sixteen 3-substituted indoles in good to excellent yields under environmentally friendly conditions has been achieved
via a three-component reaction in water of an indole, an aldehyde and malononitrile (or ethyl 2-cyanoacetate) catalysed by 5 mol% of
2
-pyrrolecarbaldiminato-Cu(II).
Keywords: 2-pyrrolecarbaldiminato-Cu(II) complex, 3-substituted indoles, multicomponent reaction, water chemistry
Multicomponent reactions (MCRs), in which more than two
starting materials are combined in the same reaction vessel to
afford a single product without isolation of any intermediate,
are powerful means for the preparation of numerous subunits
and precursors of bioactive and densely functionalised
molecules. These approaches combine multiple advantages
like high atom economy, high selectivity and overall yields,
environmental compatibility. Therefore, it is worthwhile to
develop a generally efficient and environmentally friendly
catalytic system for this class of reactions.
2-Pyrrolecarbaldiminato-based Cu complexes, which
can be easily synthesised by a simple condensation reaction
between pyrrole-2-carbaldehyde and the appropriate anilines
18
in the presence of Cu(OAc) , are air stable and water tolerant,
2
1–4
ease of operation, and the possibility of automation. The
indole core nucleus is present in many natural products and
is an important building block of numerous pharmaceuticals,
and demonstrate efficient catalytic activities in various
18–20
processes.
Recently, we have synthesised four typical
2-pyrrolecarbaldiminato-Cu(II) complexes (Fig. 1) and found
that they could efficiently catalyse Ullmann-type C-N coupling
5,6
herbicides and materials. Within the family of substituted
indole derivatives, 3-substituted indoles have attracted special
interest, because of their biological and pharmacological
activities and easy synthesis via an electrophilic replacement
21
reactions of aryl halides with imidazole (Scheme 1) and
1,3-dipolar cycloaddition reactions of benzyl halides/arylboronic
2
2,23
acids, NaN and terminal alkynes (Scheme 2).
In order to
3
7–9
reaction at the 3-position of indoles. For example, Zhou and
coworkers reported an efficient copper(II) sulphonato salen
complex-catalysed three-component reaction (3-CRs) of indole,
aldehyde, and malononitrile to provide 3-indole derivatives in
extend the scope of these catalysts, herein we present our results
on the use of 2-pyrrolecarbaldiminato-Cu(II) complexes as
catalysts for the synthesis of 3-indole derivatives.
10
Results and discussion
high yields. Subsequently, several catalytic systems, such as
1
1
12
a N,N’-dioxide-Zn(II) complex, Zn(salphen)s, Cu(OAc)2/
Our route to 3-indole derivatives is shown in Scheme 3 and
involves a Cu(II) complex-catalysed 3-CR involving an indole 5,
an aldehyde 7 and malononitrile (or ethyl 2-cyano acetate) 6 in
13
polyethylene glycol (PEG-400), tetrabutylammonium fluoride
TBAF), tetrabutylammonium glycinate ([TBA][Gly]) ionic
liquid, PEG-200, and reduced graphene oxide and zinc oxide
nanoparticales (RGO/ZnO) have been used for the same
transformation. Although these methods are highly effective,
there is still much room for improvement. For example, these
methods usually require organic solvents (e.g. CH Cl ),
14
(
15
16
17
X
N
1
0 mol% complex 4
N
N
+
R
N
H
DMSO, K PO ·3H O
R
3
4
2
120 °C
2
2
X = Cl, Br, I
additional bases (e.g. KH PO or diisopropyl ethylamine), high
2
4
catalyst loading (up to 10 mol%), high temperature (60–70 °C),
and long reaction times (up to 12 d), which leads to a high
environmental E-factor, defined as the calculated mass of
Scheme 1 2-Pyrrolecarbaldiminato-Cu(II) complexes catalysed
21
Ullmann-type C-N coupling reaction of aryl halides with imidazole.
17
waste, implying the ideal value of E-factor is zero with low
R1
N
N
R
1 mol% complexes 1 or 3
1
+
R2
N
R X
+
NaN3
N
1
: R = CH3
N
2
H O, r.t.
2
: R = t-Bu
Cu
R2
X = Br, Cl, B(OH)
2
N
N
R
3: R = Ph
4: R = Bn
Scheme 2 2-Pyrrolecarbaldiminato-Cu(II) complexes catalysed 1,3-dipolar
Fig. 1 Structures of four typical 2-pyrrolecarbaldiminato-Cu(II)
complexes 1–4.
cycloaddition reaction of benzyl halides/arylboronic acids, NaN
3
22,23
and terminal alkynes.
R1
CN
CHO
CN
+
+
complexes 1-4
R2
R1
R2
N
H
2
H O, 30 °C
R3
N
8
5
6
7
R
3
H
Scheme 3 2-Pyrrolecarbaldiminato-Cu(II) complexes catalysed three-component reaction for the synthesis of 3-indole derivatives in water at 30 °C.
Correspondent. E-mail: cesxjw@foxmail.com
*

JOURNAL OF CHEMICAL RESEARCH 2016 339
Table 1 Optimisation of the reaction conditions for the Cu(II)-complex-
Table 2 Synthesis of 3-substituted indoles (8a–p) catalysed by Cu(II)-
a
catalysed synthesis of 3-substituted indoles using a three-component
complex 2 in water (Figure 1, Scheme 3)
a
model reaction (Figure 1, Scheme 3)
1
2
3
b
Entry R
R
R
Time/h Product Yield/%
b
Entry
Catalyst/molꢀ%
Yield/%
90
96
80
86
0
76
50
1
2
3
4
5
6
7
8
9
H
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
CN
H
H
H
H
H
H
H
H
H
H
H
H
2-Me
12
15
15
15
15
12
15
15
15
15
15
15
15
15
15
24
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
8p
96
70
73
71
78
92
84
88
85
80
75
82
77
70
78
1
2
3
4
5
6
7
1/5
2/5
3/5
4/5
–
4-Me
4-OMe
4-OEt
3-Me
2-OMe
4-F
4-Cl
4-Br
2/2.5
2/1
a
1
Reaction conditions: a mixture of benzaldehyde (5, R = H) (0.4 mmol), malononitrile
6, R = CN), (0.44 mmol) and indole (7, R = H) (0.44 mmol) and varying amounts of
2
3
(
1
0
3-Cl
complexes (1–4) in H O (1 mL) was stirred for 12 h at 30 °C.
2
b
11
1-Naphthaldehyde
Cyclohexanecarboxaldehyde CN
H
H
H
H
Isolated yield.
1
2
1
3
CN
water at 30 °C. Gratifyingly, the reactions proceeded smoothly
within 12 h in the presence of the four Cu(II)-complexes with a
1
4
CN 5-OMe
CN
COOEt
1
5
5-Br
H
5
8
mol% loading to give the corresponding product in yields of
0–96%, with Cu(II)-complex 2 proving to be the most efficient
1
6
77
2
a
Reaction conditions: a mixture of various aldehydes (5) (0.4 mmol), malononitrile (6, R = CN)
or ethyl 2-cyanoacetate (6, R = CO Et) (0.44 mmol) and an indole (7) (0.44 mmol) and 5 mol%
one (Table 1, entries 1–4). A blank experiment without any
Cu(II)-complex was carried out, and no product was detected
2
2
complex 2 in H O (1 mL) was stirred for 12–24 h at 30 °C.
2
(
Table 1, entry 5). Reducing the catalyst loading from 5 mol%
to 2.5 mol% or 1 mol% led to a significantly decreased yield
Table 1, entries 6 and 7). Thus, the optimal reaction conditions
b
Isolated yield.
(
Co. Ltd. Thin-layer chromatography was carried out with Merck
silica gel GF plates. All 3-substituted indoles are characterised by
were 5 mol% Cu(II)-complex 2 as the catalyst in water at 30 °C
without any bases.
With favourable results in hand, we subjected variously
substituted indoles 7 and aldehydes 5 to reaction with
malononitrile 6 to investigate the scope of the Cu(II)-complex
2
54
1
13
H NMR, C NMR, and MS which were compared with the previously
reported data. NMR spectra were obtained on a Varian Inova-400
1
13
spectrometer ( H NMR at 400 MHz, C NMR at 100 MHz) in CDCl3
using TMS as an internal standard. Chemical shifts (δ) are given in
ppm and coupling constants (J) are given in Hz. Mass spectra were
recorded on LC-MS 2010A instrument under ESI model.
2
-catalysed 3-CRs to produce the corresponding 3-indole
derivatives 8, and the results are summarised in Table 2.
For aldehydes, we found that both electron-donating and
electron-withdrawing groups on the aromatic rings could be
converted to the desired products in good to excellent yields
within 15 h, with electron-withdrawing groups giving slightly
higher yields (entries 1–10). Notably, 2-methoxybenzaldehyde
and 1-naphthaldehyde also reacted well under the standard
conditions, which indicated that steric hindrance has little
effect on the results (entries 6 and 11). The reaction of an
aliphatic aldehyde, such as cyclohexanecarbaldehyde, also
gave the product in 82% yield (entry 12). Next, the 3-CRs
were performed with three substituted indoles, 2-methylindole,
Three component reactions; general procedure
A 25 mL Schlenk tube was charged with Cu(II)-complex 2
(
(
0.02 mmol), aldehyde 5 (0.4 mmol), nitrile 6 (0.44 mmol) and indole 7
0.44 mmol) to which water (1 mL) was added. The mixture was stirred
at 30 °C and monitored by TLC until the aldehyde had been consumed.
The reaction mixture was extracted with ethyl acetate (3 × 10 mL),
washed with water and brine, dried over anhydrous Na SO , and
2
4
concentrated in vacuo. The residue was purified by flash column
chromatograph on silica gel with PE/EtOAc as the eluent to provide the
desired products 8a–p.
16
2-((1H-Indol-3-yl)(phenyl)methyl)malononitrile (8a): Yellow solid
2
4
1
5
-methoxyindole and 5-bromoindole, which gave very good
(96%), m.p. 74–75 °C [lit. m.p. 76–78 °C]; H NMR: δ 8.24 (br s, 1H),
7.36–7.44 (m, 7H), 7.28 (d, J = 8.0 Hz, 1H), 7.20–7.25 (m, 1H), 7.06
yields of 77, 70, and 78%, respectively (entries 13–15). Finally,
the study was further extended to ethyl 2-cyano acetate, another
active methylene compound, and the product 8p was obtained in
(
d, J = 7.2 Hz, 1H), 4.92 (d, J = 6.4 Hz, 1H), 4.43 (d, J = 6.4 Hz, 1H);
13
C NMR: δ 137.1, 136.2, 129.2, 128.8, 128.2, 125.9, 123.1, 122.2, 120.3,
–
1
18.7, 112.5, 112.3, 112.2, 111.6, 44.2, 29.7; MS (ESI): m/z = 270 [M – H] .
77% yield (entry 16) as an inseparable diastereomeric mixture
16
2
-((1H-Indol-3-yl)(p-tolyl)methyl)malononitrile (8b): Yellow solid
(1:1).
1
(70%), m.p. 185–186 °C; H NMR: δ 8.23 (br s, 1H), 7.36–7.38 (m, 1H),
7
.28–7.34 (m, 4H), 7.21–7.26 (m, 1H), 7.16–7.20 (m, 2H), 7.04–7.08 (m, 1H),
Conclusion
13
4.87 (d, J = 6.4 Hz, 1H), 4.40 (d, J = 6.4 Hz, 1H), 2.33 (s, 3H); C NMR:
In conclusion, we have developed
a
practical and
δ 138.6, 136.3, 134.1, 129.8, 128.0, 125.9, 123.0, 122.1, 120.2, 118.8, 112.7,
promising method for 3-substituted indoles synthesis by
-pyrrolecarbaldiminato-Cu(II) complex-catalysed 3-CRs of
–
112.4, 112.3, 111.6, 43.9, 29.7, 21.1; MS (ESI): m/z= 284 [M – H] .
2
16
2
-((1H-Indol-3-yl)(4-methoxyphenyl)methyl)malononitrile (8c):
indoles, aldehydes and malononitrile/ethyl 2-cyano acetate in
water without any bases. The advantages of this method include
good substrate generality, a readily-available catalyst, and
environmentally friendly reaction conditions.
1
Pale-yellow solid (73%), m.p. 164–165 °C; H NMR: δ 8.26 (br s, 1H),
.35–7.41 (m, 4H), 7.28 (s, 1H), 7.20–7.25 (m, 1H), 7.05–7.08 (m, 1H),
7
6
1
1
.90 (d, J = 8.8 Hz, 2H), 4.89 (d, J = 6.0 Hz, 1H), 4.41 (d, J = 6.0 Hz,
13
H), 3.80 (s, 3H); C NMR: δ 159.8, 136.3, 129.4, 129.0, 125.9, 123.1,
21.9, 120.3, 118.8, 114.5, 112.8, 112.3, 112.2, 111.5, 55.3, 43.6, 29.9;
Experimental
–
MS (ESI): m/z = 300 [M – H] .
All reagents were purchased from commercial suppliers and used
without further purification. All reactions were carried out under air
using magnetic stirring. Column chromatography was performed with
silica gel (200–300 mesh) purchased from Qingdao Haiyang Chemical
2-((4-Ethoxyphenyl)(1H-indol-3-yl)methyl)malononitrile (8d): Pale-
yellow solid (71%), m.p. 142–144 °C; H NMR: δ 8.25 (br s, 1H), 7.32–7.39
(m, 4H), 7.19–7.27 (m, 2H), 7.04–7.08 (m, 1H), 6.87–6.96 (m, 2H), 4.87 (d,
J = 6.0 Hz, 1H), 4.40 (d, J = 6.0 Hz, 1H), 4.00 (q, J = 6.8 Hz, 2H), 1.40 (t,
1

3
40 JOURNAL OF CHEMICAL RESEARCH 2016
1
3
13
J = 6.8 Hz, 3H); C NMR: δ 159.2, 136.3, 129.4, 128.9, 125.9, 123.1, 121.9,
20.2, 118.8, 114.9, 112.8, 112.4, 112.3, 111.5, 77.4, 77.0, 76.7, 63.5, 43.6,
(d, J = 6.4 Hz, 1H), 4.42 (d, J = 6.4 Hz, 1H), 3.72 (s, 3H); C NMR:
1
δ 154.4, 137.1, 131.4, 129.2, 128.7, 128.2, 126.3, 122.9, 113.1, 112.3,
112.2, 112.1, 100.8, 55.8, 44.2, 29.6; MS (ESI): m/z = 300 [M – H] .
–
–
2
9.9, 14.8; MS (ESI): m/z = 314 [M – H] .
-((1H-Indol-3-yl)(m-tolyl)methyl)malononitrile (8e):
solid (78%), m.p. 180–182 °C; H NMR: δ 8.27 (s, 1H), 7.08–7.41 (m,
H), 4.96 (d, J = 5.6 Hz, 1H), 4.33 (d, J = 5.6 Hz, 1H), 2.35 (s, 3H);
C NMR: δ 138.9, 137.1, 136.2, 129.5, 129.0, 128.8, 125.9, 125.1, 123.1,
22.2, 120.3, 118.7, 112.6, 112.3, 112.3, 111.5, 44.1, 29.7, 21.5; MS
ESI): m/z = 284 [M – H] .
- ((1H-Indol-3-yl)(2-methoxyphenyl)methyl)malononitrile
8f): Yellow solid (92%), m.p. 172–174 °C; H NMR: δ 8.31 (s, 1H),
.88–7.42 (m, 9H), 5.43 (t, J = 6.0 Hz, 1H), 4.75 (t, J = 6.0 Hz, 1H), 4.00
d, J = 5.6 Hz, 3H); C NMR: δ 146.0, 136.3, 134.2, 132.7, 130.7, 129.6,
29.4, 127.3, 126.2, 125.5, 125.4, 123.5, 123.1, 122.0, 120.3, 118.5, 39.3,
8.6; MS (ESI): m/z = 300 [M – H] .
-((4-Fluorophenyl)(1H-indol-3-yl)methyl)malononitrile (8g): Yellow
16
15
2
Yellow
2-((5-Bromo-1H-indol-3-yl)(phenyl)methyl)malononitrile
(8o):
1
15
1
Yellow solid (78%), m.p. 169–170 °C [lit. m.p. 170–172 °C]; H NMR:
δ 8.33 (br s, 1H), 7.43–7.44 (m, 2H), 7.41–7.42 (m, 4H), 7.38–7.39 (m,
1H), 7.29–7.32 (m, 2H), 4.88 (d, J = 6.4 Hz, 1H), 4.41 (d, J = 6.4 Hz,
9
13
13
1
(
1H); C NMR: δ 136.6, 134.9, 129.3, 128.9, 128.1, 127.7, 126.2, 123.3,
121.3, 113.6, 113.0, 112.1, 112.0, 112.0, 43.9, 29.7; MS (ESI): m/z = 348
–
–
2
[M – H] .
Ethyl
16
1
14
(
2-cyano-3-(1H-indol-3-yl)-3-phenylpropanoate
(8p):
6
(
Yellow solid (77%), m.p. 150–152 °C; spectral data for 1:1 inseparable
diastereomeric mixture: H NMR: δ 8.25 (s, 1H), 8.20 (s, 1H), 7.44–7.46
(m, 4H), 7.21–7.38 (m, 4H), 7.13–7.19 (m, 2H), 6.99–7.06 (m, 2H), 5.10
(d, J = 6.8 Hz, 1H), 5.03 (d, J = 6.8 Hz, 1H), 4.32 (d, J = 6.8 Hz, 1H),
4.19 (d, J = 6.8 Hz, 1H), 4.11 (q, J = 7.2 Hz, 2H), 4.10 (q, J = 7.2 Hz, 2H),
1.09 (t, J = 7.2 Hz, 3H), 1.06 (t, J = 7.2 Hz, 3H); C NMR: δ 165.3, 165.3,
139.7, 138.6, 136.3, 136.1, 130.2, 128.8, 128.7, 128.5, 128.4, 128.0, 127.9,
127.7, 126.7, 126.1, 122.7, 122.6, 122.2, 122.1, 119.9, 119.8, 119.0, 118.7,
16.3, 116.1, 114.8, 113.4, 111.4, 111.3, 62.9, 62.9, 45.1, 44.3, 43.2, 43.2,
13
1
1
2
–
14
2
1
13
solid (84%), m.p. 65–66 °C; H NMR: δ 8.35 (br s, 1H), 7.37–7.40 (m, 3H),
.24–7.30 (m, 3H), 7.03–7.13 (m, 3H), 4.88 (d, J = 6.4 Hz, 1H), 4.37 (d,
7
1
3
J = 6.4 Hz, 1H); C NMR: δ 164.0, 161.5, 136.3, 133.0, 130.1, 130.0, 125.7,
23.2, 122.1, 120.36, 118.8, 116.3, 116.1, 112.4, 112.2, 111.8, 43.4, 29.7; MS
1
(
1
–
ESI): m/z = 288 [M – H] .
-((4-Chlorophenyl)(1H-indol-3-yl)methyl)malononitrile (8h): Yellow
solid (88%), m.p. 73–74 °C [lit. m.p. 70–72 °C]; H NMR: δ 8.27 (br s,
H), 7.35–7.33 (m, 1H), 7.30 (s, 4H), 7.21–7.26 (m, 2H), 7.19–7.23 (m,
H), 7.03–7.07 (m, 1H), 4.83 (d, J = 6.4 Hz, 1H), 4.34 (d, J = 6.4 Hz, 1H);
–
13.8, 13.8; MS (ESI): m/z = 317 [M – H] .
16
2
2
4
1
We gratefully acknowledge financial support from the Training
Program for Distinguished Youth Scholars of Shihezi University
(no. 2014ZRKXJQ05) and the Youth Fund of Shandong
Academy of Sciences (2014QN020).
1
1
1
3
C NMR: δ 136.3, 135.6, 134.8, 129.6, 129.4, 125.68, 123.3, 122.1, 120.5,
18.6, 112.1, 112.0, 111.9, 111.7, 43.6, 29.5; MS (ESI): m/z= 304 [M – H] .
–
1
16
Electronic Supplementary Information
2
-((4-Bromophenyl)(1H-indol-3-yl)methyl)malononitrile
(8i):
Yellow solid (85%), m.p. 180–182 °C; H NMR: δ 8.32 (br s, 1H),
.49–7.52 (m, 2H), 7.38–7.40 (m, 1H), 7.28–7.33 (m, 3H), 7.22–7.26 (m,
H), 7.07–7.11 (m, 1H), 4.88 (d, J = 6.4 Hz, 1H), 4.41 (d, J = 6.4 Hz, 1H);
1
1
13
H NMR and C NMR spectra of compounds 8a–p are
7
available through:
2
stl.publisher.ingentaconnect.com/content/stl/jcr/supp-data
13
C NMR: δ 136.3, 136.1, 132.4, 129.9, 125.7, 123.3, 122.9, 122.1, 120.5,
18.6, 112.0, 111.9, 111.9, 111.7, 43.7, 29.4; MS (ESI): m/z = 348 [M – H] .
-((3-Chlorophenyl)(1H-indol-3-yl)methyl)malononitrile
Yellow solid (80%), m.p. 176–179 °C [lit. m.p. 179–181 °C]; H NMR:
δ 8.32 (br s, 1H), 7.40–7.41 (m, 2H), 7.37–7.38 (m, 1H), 7.33–7.36 (m,
H), 7.26–7.31 (m, 2H), 7.22–7.25 (m, 1H), 4.90 (d, J = 6.4 Hz, 1H),
.42 (d, J = 6.4 Hz, 1H); C NMR: δ 139.1, 136.3, 135.1, 130.5, 129.1,
28.4, 126.4, 125.7, 123.3, 122.2, 120.5, 118.5, 111.9, 111.9, 111.8, 111.7,
3.7, 29.5; MS (ESI): m/z = 304 [M – H] .
- ((1H-Indol-3-yl)(naphthalen-2-yl) methyl) malononitrile
8k): Yellow solid (75%), m.p. 73–75 °C; H NMR: δ 8.23 (s, 1H),
.07–8.08 (m, 1H), 7.93–7.95 (m, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.61
d, J = 6.8 Hz, 1H), 7.54–7.56 (m, 2H), 7.46 (t, J = 8.0 Hz, 1H), 7.36
d, J = 8.8 Hz, 2H), 7.30 (d, J = 2.4 Hz, 1H), 7.21–7.25 (m, 1H),
.06–7.10 (m, 1H), 5.43 (d, J = 6.0 Hz, 1H), 4.59 (t, J = 6.0 Hz, 1H);
C NMR: δ 146.0, 136.3, 134.2, 132.7, 130.7, 129.6, 129.4, 127.3,
26.2, 125.5, 125.4, 123.5, 123.0, 121.9, 120.3, 118.5, 39.3, 28.7; MS
ESI): m/z = 320 [M – H] .
-(Cyclohexyl(1H-indol-3-yl)methyl)malononitrile (8l): Yellow
solid (82%), m.p. 164–165 °C [lit. m.p. 162–164 °C]; H NMR:
δ 8.25 (br s, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.38–7.40 (d, J = 8.0 Hz,
H), 7.28–7.29 (m, 1H), 7.22–7.25 (m, 1H), 7.15–7.19 (m, 1H), 4.21
d, J = 5.2 Hz, 1H), 3.38 (dd, J = 9.2, 5.6 Hz, 1H), 2.03–2.08 (m, 1H),
.95–1.99 (m, 1H), 1.81–1.85 (m, 1H), 1.64–1.66 (m, 3H), 1.33–1.40
m, 1H), 1.11–1.13 (m, 3H), 0.88–0.97 (m, 1H); C NMR: δ 135.8,
27.1, 122.8, 122.2, 120.2, 118.7, 112.8, 112.7, 112.3, 111.5, 43.9, 40.6,
1.6, 30.5, 27.7, 25.9, 25.9, 25.9; MS (ESI): m/z = 276 [M – H] .
-((2-Methyl-1H-indol-3-yl)(phenyl)methyl)malononitrile (8m):
Yellow solid (77%), m.p. 160–162 °C [lit. m.p. 159–161 °C]; H NMR:
δ 8.07 (br s, 1H), 7.46–7.48 (m, 2H), 7.38–7.42 (m, 2H), 7.28–7.36 (m,
H), 7.15–7.19 (m, 1H), 7.05–7.09 (m, 1H), 4.98 (d, J = 9.6 Hz, 1H),
.70 (d, J = 9.6 Hz, 1H), 2.46 (s, 3H); C NMR: δ 137.2, 135.4, 134.0,
29.0, 128.0, 127.4, 126.2, 121.8, 120.2, 118.3, 112.8, 112.5, 111.0,
–
1
Received 3 February 2016; accepted 29 February 2016
Paper 1603899 doi: 10.3184/174751916X14622783380474
Published online: 16 May 2016
1
6
2
(8j):
2
4
1
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