Calix[6]arene sulfonic acids catalysed Michael reactions of indoles with α,β-unsaturated ketones in water assisted by microwave radiation

Article abstract of DOI:10.3184/174751913X13734725288804

Michael reactions of indoles with α,β-unsaturated ketones were carried out under microwave irradiation in water, affording the corresponding products in good to excellent yields. The calix[6]arene sulfonic acids bearing pendent aliphatic chains, as effici

Full text of DOI:10.3184/174751913X13734725288804

476 RESEARCH PAPER
AUGUST, 476–479
JOURNAL OF CHEMICAL RESEARCH 2013
Calix[6]arene sulfonic acids catalysed Michael reactions of indoles with
α,β-unsaturated ketones in water assisted by microwave radiation
Yuanyuan Xie*, Linfeng Mao and Lehuan Li
Key Laboratory for Green PharmaceuticalTechnologies and Related Equipment of Ministry of Education, College of Pharmaceutical
Sciences, Zhejiang University ofTechnology, Hangzhou 310014, P. R. China
Michael reactions of indoles with α,β-unsaturated ketones were carried out under microwave irradiation in water,
affording the corresponding products in good to excellent yields. The calix[6]arene sulfonic acids bearing pendent
aliphatic chains, as efficient surfactant-type acid catalysts, can be recovered after simple work-up and reused directly
several times without loss of catalytic activity.
Keywords: Michael reactions, water-soluble calixarene, microwave irradiation
Indole and its derivatives are important intermediates because
of their pharmacologically and biologically interesting activi-
ties.1 Michael addition of indoles to electron-deficient α,β-
unsaturated carbonyl compounds has become one of the most
important C–C bond formation in organic synthesis. Usually,
Lewis or protonic acids, such as SbCl3, ZrCl4, Bi(OTf)3, PTSA
or CF3CO2H, have been applied to catalyse the conjugate
addition of indoles with α,β-unsaturated ketones in organic
solvents.2–6 However, these methods have obvious disadvan-
tages in view of green chemistry and atom economy. For
example, Lewis acids often require normality and are difficult
to recycle. In addition, some heavy metals and organic
solvents are harmful to the environment. Recently, aqueous
reactions without using harmful organic solvents have attracted
interest because water is an easily available, economical, safe
and environmentally benign solvent.7 Gu8 developed a novel
neutral catalyst system derived from silica gel-supported
sodium sulfonate with ionic liquid for Michael reactions in
water. More recently, Ma9 reported that in the presence of a
carbon-based solid acid, the conjugate addition of indole
derivatives with α,β-unsaturated carbonyl compounds could be
achieved. However, for these methods, a long reaction time is
needed and their scope of application is limited. Thus, an effi-
cient and universal aqueous Michael addition reaction is still in
demand. Shinkai10–12 reported a series of water-soluble calix-
arene derivatives. Subsequently, hexasulfonated calix[6]arenes
with various substitutes gained attention because of their
highly effective surfactant activities and molecular recognition
abilities. Para-Bu-calix[6]arene-SO3H as a protonic acid
catalyst was found to be a highly effective surfactant in the
allylic alkylation with allyl alcohols in water.13 Also, the
synthesis of bis(indolyl)methanes derived from indoles and
aldehydes in water was achieved, using p-sulfonic acid
calix[4]arene as a reusable organocatalyst.14 We assumed that
the use of these calixarenene derivatives as surfactant-type
acid catalysts can improve the efficiency of catalytic conjugate
addition between indoles and α,β-unsaturated ketones in
water. We now report the water-soluble calixarene-catalysed
Michael reaction of indoles to α,β-unsaturated ketones under
microwave irradiation in water.
(R = H) and 4b (R = CH3) were employed as Brønsted acids
(5 mol%) in the reaction, respectively. But the yields obtained
(4a: 56%, 4b: 58%) were not as good as expected, although the
reaction time was prolonged to 48h. However, when 4c and 4d
bearing longer alkyl groups were used instead of 4a and 4b
under the same conditions, relatively higher yields were
achieved (72%, 68%, respectively). It is reported that surfac-
tant-type calixarene sulfonic acid bearing proper aliphatic
chains is inclined to form micelles in water.13 So the formation
of micelles in water in the course of the reaction contributes
to the improvement of catalytic activity of 4c and 4d. For
comparison, PTSA was employed under the same reaction
conditions. Apparently, PTSA showed a low catalytic activity
and only 41% yield was obtained in the presence of 30 mol%
of PTSA for 48h. It was clear that 4c was the optimal catalyst
in the reaction of indoles with α,β-unsaturated ketones. When
the reaction temperature was raised from 25 to 70 °C, the
solubility of indole was greatly enhanced, as the reaction was
accelerated. Thus, the reaction time was greatly shortened and
the yield of adduct product 3a was significantly improved to
88% (Table 1, entry 8). When this protocol was applied in
combination with microwave irradiation, the yield of 3a
increased to a higher level and the reaction was completed in
20 min (Table 1, entry 9). The yield of 3a decreased as soon as
the amount of catalyst was reduced. However, no apparent
improvement was observed when the amount of catalyst was
increased to 10 mol%. So far, the best result has been achieved
when the reaction was catalysed by 5 mol% of 4c in water
under microwave irradiation.
Based on the initial success, the reaction was subsequently
carried out between various α,β-unsaturated ketones and dif-
ferent indoles in the presence of catalyst 4c (5 mol%) in water
under microwave irradiation, producing adduct 3 in good
yields (70–97%) (Table 2). When the H atom of chalcone was
Table 1 Screening of the catalysts based on the reaction of 1a
with 2a in watera
Entry
Catalyst/mol%
T/°C
Time
Yield of 3a/%b
1
2
none
4a (5)
4b (5)
4c (5)
4d (5)
PTSA (30)
4c (5)
4c (5)
4c (5)
4c (10)
4c (3)
25
25
25
25
25
25
50
70
70c
70c
70c
48h
48h
0
56
58
72
68
41
83
88
96
98
85
Results and discussion
3
48h
Initially, we explored the influence of different catalysts as
shown in Table 1. The reaction of indole 1a with chalcone
2a was carried out in water as a reaction model (Scheme 1).
PTSA and several water-soluble calix[6]arene sulfonic acids
derivatives used as catalysts were investigated. Calix[6]arene
sulfonic acids bearing pendant aliphatic chains(Fig. 1: 4a–d)
were synthesised on the basis of a report by Shinkai.10 First, 4a
4
48h
5
48h
6
48h
7
12h
8
5h
9
20 min
20 min
20 min
10
11
a Reaction conditions: indole (1a, 1.2 mmol) and chalcone (2a,
1 mmol) were carried out in 2 mL water. b Isolated yield. c Under
microwave irradiation.
* Correspondent. E-mail: pharmlab@zjut.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2013 477
Scheme 1 Michael reaction of indole 1a with chalcone 2a in water.
In conclusion, the calix[6]arene sulfonic acids bearing
pendent aliphatic chains, as efficient inverse phase-transfer
catalysts, performs highly effective catalytic reactivity in the
Michael addition of indoles with various α,β-unsaturated
ketones in water. The methodology developed in the present
work is environmentally friendly, which avoids the use of
organic solvents and the reaction time can be shortened to min-
utes under microwave irradiation. Furthermore, the catalyst
can be recovered from an aqueous reaction system and keeps
excellent catalytic activity after reusing several times.
Fig. 1 The surfactant-type catalyst of calix[6]arene sulfonic
acids bearing pendant aliphatic chains.
Experimental
replaced by other groups, the yield of adduct experienced a
small decrease (Table 2, entries 2–5). Indole and 5-methoxyin-
dole both exhibited good reactivity in the reaction with chal-
cone and its derivatives. When the 2-position of indole was
substituted by methyl group, the yield of adduct experienced a
slight drop because of the steric effect (Table 2, entries 11 and
12). The nucleophilicity of indole decreased significantly
when the 5-position of indole was substituted by a strong elec-
tron-withdrawing group, such as the nitro group. For example,
only a trace of adduct 3m could be detected when substituted
chalcone was reacted with 5-nitroindole instead of indole
(Table 2, entry 13). Besides, linear-chain α,β-unsaturated
carbonyl compounds were also investigated and much higher
reactivity was observed, especially for vinyl ketone, which
was so active that the microwave radiation was not necessary
(Table 2, entries 15 and 17).
All solvents and reagents were commercially available and used
without further purification. Deionised water was used as solvent for
the Michael reaction. Microwave irradiation experiments were carried
out in a Discover-CEM mono mode microwave apparatus. Flash
column chromatography used silica gel (200–400 mesh), purchased
from Qingdao Haiyang Chemical Co., Ltd. Ion exchange was carried
out using 732-strong acidic styrene. Melting points were recorded
on a Büchi B-540 apparatus and uncorrected. Mass spectra were
obtained on a Finnigan LCQ-Advantage. High resolution mass
spectral (ESI-HRMS) were measured on a Bruker micrOTOF-QII. 1H
NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on
a Varian-400 instrument. IR spectra were performed using KBr pellets
on a Nicolet Aviatar-370 equipment. The purity of product 3k was
determined by HPLC (Agilent 1200) analyses.
Synthesis of Michael adduct 3a; typical procedure
Indole (1.2 mmol), chalcone (1 mmol) 5 mol% of 4c and water (2 mL)
were added to a 10 mL microwave tube. The reaction mixture
was stirred and heated to 70 °C for 20 min with microwave irradiation
(150 W). The reaction mixture was cooled to room temperature and
extracted with ethyl acetate (3×5 mL) three times. Then the organic
solvents were combined and dried over anhydrous sodium sulfate.
The recycling experiment was performed and a high cata-
lytic activity of 4c remained. Over 90% yield of adduct could
still be obtained even the catalyst had been reused five times
(Table 2, entry1).
Table 2 Michael-type reactions of indoles with α,β-unsaturated ketones in watera
Entry
1
R1
R2
R3
Product
Time/min
20
Yield/%b
H (1a)
Ph
Ph
3a
96, 93c, 91d, 92e,
90f, 90g
91
2
3
H
H
H
H
p-MeC6H4
p-FC6H4
p-ClC6H4
m-MeOC6H4
Ph
Ph
p-MeC6H4
p-ClC6H4
Ph
Ph
Ph
p-MeC6H4
Ph
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
20
35
30
30
20
20
35
30
30
30
30
50h
20
15i
20
15i
20
73
4
71
5
84
6
5-MeO (1f)
5-MeO
5-MeO
5-MeO
5-MeO
2-Me (1k)
2-Me
93
7
p-MeC6H4
p-FC6H4
p-ClC6H4
Ph
87
8
74
9
78
10
11
12
13
14
15
16
17
18
2-Furyl
Ph
Me
75
Ph
86
n-C4H9
p-FC6H4
H
87
5-NO2 (1m)
5-NO2
H
p-MeC6H4
Me
trace
71
H
Me
97
H
n-C4H9
H
Me
93
5-MeO
5-MeO
Me
92
n-C4H9
Me
92
a Reaction conditions: indole (1.2 mmol), ketones (1 mmol), in 2 mL H2O, assisted by microwave radiation, unless specified other-
wise. b Isolated yield. c Reused once; d reused twice; e reused a third time; f reused a fourth time; g reused a fifth time. h Proceeded at
90 °C; i reacted at 0 °C without microwave irradiation.

478 JOURNAL OF CHEMICAL RESEARCH 2013
Scheme 2 Synthesis of indole derivatives 3 via Michael reaction.
1344, 1215, 1030, 800 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.92–7.90
(m, 2H), 7.83 (s, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.40 (t, J = 7.6 Hz, 2H),
7.21 (d, J = 8.8 Hz, 2H), 7.16 (d, J = 8.8 Hz, 1H) 7.04 (d, J = 8.0 Hz,
2H), 6.92 (d, J = 2.4 Hz, 1H), 6.83 (d, J = 2.4 Hz, 1H), 6.77 (dd, J =
8.8, 2.4 Hz, 1H), 4.96 (t, J = 7.2 Hz, 1H), 3.77 (dd, J = 16.8, 6.8 Hz,
1H), 3.72 (s, 3H), 3.68 (dd, J = 16.8, 7.6 Hz, 1H), 2.27 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 198.4, 153.7, 141.0, 137.1, 135.5, 132.7,
131.7, 129.0, 128.4, 128.0, 127.5, 127.0, 122.1, 119.2, 112.1, 111.6,
101.7, 55.9, 45.3, 38.0, 21.1; MS (ESI): m/z 392 [M + Na]+; HRMS-
ESI: calcd for C25H23NNaO2: 392.1621; found: 392.1620.
3-(4-Fluorophenyl)-3-(5-methoxy-1H-indol-3-yl)-1-(p-tolyl)propan-
1-one (3h): White solid; m.p. 148–149 °C; IR: νmax 3351, 3056, 1669,
1461, 1360, 1222, 1211, 800 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.90
(s, 1H), 7.81 (d, J = 8.0 Hz, 2H), 7.28–7.25 (m, 2H), 7.22–7.16 (m,
3H), 6.92–6.88 (m, 3H), 6.80–6.77 (m, 2H), 4.98 (t, J = 7.2 Hz, 1H),
After filtration, the filtrate was concentrated in vacuo and the residue
was purified by column chromatography (petroleum ether/ethyl
acetate, 6:1) to afford 3a as a white solid.
Recycling of catalyst 4c: After completion of the reaction, the reac-
tion mixture was extracted with ethyl acetate (3×5 mL). The remain-
ing aqueous phase with catalyst 4c could be directly reused in the next
Michael reaction.
3-(1H-Indol-3-yl)-1,3-diphenylpropan-1-one (3a): White solid;
m.p. 129–130 °C, (lit.15 126–129 °C); IR: νmax 3408, 3056, 2921, 1676,
1457, 1337, 742 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.94 (br s, 1H),
7.90 (d, J = 7.2 Hz, 2H), 7.51 (t, J = 7.2 Hz, 1H), 7.42–7.38 (m, 3H),
7.34–7.28 (m, 3H), 7.25–7.21 (m, 2H), 7.13 (dt, J = 12.8, 6.4 Hz, 2H),
7.01–6.97 (m, 2H), 5.06 (t, J = 7.2 Hz, 1H), 3.81 (dd, J = 16.8, 6.8 Hz,
1H), 3.71 (dd, J = 16.8, 7.6 Hz, 1H).
3-(1H-Indol-3-yl)-1-phenyl-3-(p-tolyl)propan-1-one (3b): White
solid; m.p. 125–128 °C, (lit.16 127–128 °C); IR: νmax 3427, 3056, 1673,
1447, 1337, 1205, 809, 746 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.90
(d, J = 8.0 Hz, 3H), 7.51 (t, J = 7.2 Hz, 1H), 7.43–7.38 (m, 3H), 7.28
(d, J = 8.4 Hz, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.12 (t, J = 7.2 Hz, 1H),
7.03 (d, J = 7.6 Hz, 2H), 6.99 (t, J = 7.6 Hz, 1H), 6.95 (s, 1H), 5.01
(t, J = 7.2 Hz, 1H), 3.79 (dd, J = 16.4, 6.8 Hz, 1H), 3.69 (dd, J = 16.8,
7.6 Hz, 1H), 2.27 (s, 3H).
3-(4-Fluorophenyl)-3-(1H-indol-3-yl)-1-(p-tolyl)propan-1-one
(3c): White solid; m.p. 142–144 °C; IR: νmax 3405, 3056, 1681, 1456,
1217, 1181, 810, 742 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.98 (br s,
1H), 7.81 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.0 Hz, 1H), 7.30–7.25 (m,
3H), 7.20 (d, J = 8.0 Hz, 2H), 7.15–7.11 (m, 1H), 7.01–6.96 (m, 1H),
6.94–6.87 (m, 3H), 5.02 (t, J = 7.2 Hz, 1H), 3.75 (dd, J = 16.4, 6.4 Hz,
1H), 3.64 (dd, J = 16.8, 8.0 Hz, 1H), 2.38 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 197.8, 161.1 (1JCF = 242 Hz), 143.8, 139.8, 136.4,
134.4, 129.13, 129.05, 128.1, 126.3, 122.1, 121.2, 119.3, 119.0,
115.01, 115.0 (2JCF = 21 Hz), 111.1, 45.1, 37.6, 21.7; MS (ESI): m/z
380 [M + Na]+; HRMS-ESI: calcd for C24H20FNNaO: 380.1421;
found: 380.1404.
1,3-bis(4-Chlorophenyl)-3-(1H-indol-3-yl)propan-1-one (3d): White
solid; m.p. 138–140 °C, (lit.17 136–138 °C); IR: νmax 3420, 3043,
1673, 1458, 1337, 1201, 1091, 744 cm−1; 1H NMR (400 MHz, CDCl3)
δ 7.98 (br s, 1H), 7.82 (d, J = 8.4 Hz, 2H), 7.39–7.36 (m, 3H), 7.30 (d,
J = 8.0 Hz, 1H), 7.23–7.18 (m, 4H), 7.14 (t, J = 7.2 Hz, 1H), 7.01 (t,
J = 7.2 Hz, 1H), 6.94–6.92 (m, 1H), 5.00 (t, J = 7.6 Hz, 1H), 3.75 (dd,
J = 16.8, 6.4 Hz, 1H), 3.64 (dd, J = 16.8, 8.0 Hz, 1H); MS (ESI): m/z
432 ([M + K]+, 100%), 434 ([M + K + 2]+, 66%), 436 ([M + K + 4]+,
10%); HRMS-ESI: calcd for C23H17Cl2NNaO: 416.0579; found:
416.0586.
3.77–3.68 (m, 4H), 3.63 (dd, J = 16.8, 8.0 Hz, 1H), 2.39 (s, 3H); 13
C
NMR (100 MHz, CDCl3) δ 197.8, 161.1 (1JCF = 242 Hz), 153.6, 143.8,
139.7, 134.4, 131.6, 129.13, 129.05, 128.1, 126.7, 121.9, 118.8, 115.0
(2JCF = 21 Hz), 112.1, 111.7, 101.3, 55.8, 45.0, 37.6, 21.7; MS (ESI):
m/z 410 [M + Na]+; HRMS-ESI: calcd for C25H22FNNaO2: 410.1527;
found: 410.1513.
3-(4-Chlorophenyl)-3-(5-methoxy-1H-indol-3-yl)-1-phenylpropan-
1-one (3i): White solid; m.p. 145–146 °C, (lit.19 139–140 °C); IR: νmax
1
3409, 3056, 1673, 1483, 1356, 1209, 1034, 804, 751 cm−1; H NMR
(400 MHz, CDCl3) δ 7.91–7.90 (m, 3H), 7.53 (t, J = 7.6 Hz, 1H), 7.42
(t, J = 7.6 Hz, 2H), 7.25 (t, J = 7.6 Hz, 2H), 7.20–7.18 (m, 3H), 6.92
(d, J = 2.4 Hz, 1H), 6.81–6.78 (m, 2H), 4.98 (t, J = 7.2 Hz, 1H),
3.80–3.73 (m, 4H), 3.66 (dd, J = 16.8, 8.0 Hz, 1H).
1-(Furan-2-yl)-3-(5-methoxy-1H-indol-3-yl)-3-phenylpropan-1-one
(3j): White solid; m.p. 117–118 °C; IR: νmax 3416, 3023, 1663, 1464,
1
1345, 1209, 1168 cm−1; H NMR (400 MHz, CDCl3) δ 7.91 (s, 1H),
7.51 (s, 1H), 7.32 (d, J = 7.2 Hz, 2H), 7.22 (t, J = 7.2 Hz, 2H), 7.16–
7.09 (m, 3H), 6.97 (d, J = 2.0 Hz, 1H), 6.82 (d, J = 2.0 Hz, 1H), 6.77
(dd, J = 8.8, 2.0 Hz, 1H), 6.45 (d, J = 2.8 Hz, 1H), 4.97 (t, J = 7.6 Hz,
1H), 3.71 (s, 3H), 3.64 (dd, J = 16.0, 6.8 Hz, 1H), 3.53 (dd, J = 16.0,
7.6 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 187.5, 153.4, 152.6,
146.1, 143.7, 131.5, 128.2, 127.6, 126.8, 126.1, 122.1, 118.4, 117.1,
112.1, 112.0, 111.7, 101.3, 55.8, 44.9, 38.2; MS (ESI): m/z 368
[M + Na]+; HRMS-ESI: calcd for C22H19NNaO3: 368.1257; found:
368.1225.
3-(2-Methyl-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3k): Yellow
solid; m.p. 116–117 °C, (lit.17 115–116 °C); IR: νmax 3403, 3056,
1
1681, 1459, 1340, 746 cm−1; H NMR (400 MHz, CDCl3) δ 7.85 (d,
J = 8.0 Hz, 2H), 7.71 (s, 1H), 7.46 (t, J = 7.2 Hz, 2H), 7.37–7.33 (m,
4H), 7.22–7.19 (m, 3H), 7.12 (t, J = 7.2 Hz, 1H), 7.04 (t, J = 7.2 Hz,
1H), 6.97 (t, J = 7.2 Hz, 1H), 5.08 (t, J = 7.2 Hz, 1H), 3.98–3.80 (m,
2H), 2.41 (s, 3H); MS (ESI): m/z 378 [M + K]+; purity:96% (HPLC:
Daicel Chiral OD-H, 25% iPrOH: 75% n-hexane).
3-(1H-Indol-3-yl)-3-(3-methoxyphenyl)-1-phenylpropan-1-one
(3e): White solid; m.p. 119–121 °C, (lit.18 118–119 °C); IR: νmax 3383,
1
3037, 1677, 1455, 1275, 1221, 745, 608 cm−1; H NMR (400 MHz,
CDCl3) δ 7.96 (s, 1H), 7.90 (d, J = 8.0 Hz, 2H), 7.50 (t, J = 7.2 Hz,
1H), 7.44 (d, J = 8.0 Hz, 1H), 7.39 (t, J = 8.0 Hz, 2H), 7.26 (d, J = 8.0
Hz, 1H), 7.17–7.09 (m, 2H), 6.99 (t, J = 7.2 Hz, 1H), 6.93–6.88 (m,
3H), 6.68 (dd, J = 8.4, 2.0 Hz, 1H), 5.02 (t, J = 7.2 Hz, 1H), 3.78 (dd,
J = 16.8, 7.2 Hz, 1H), 3.72–3.66 (m, 4H).
3-(5-Methoxy-1H-indol-3-yl)-1,3-diphenylpropan-1-one (3f): White
solid; m.p. 143–146 °C, (lit.18 149–151 °C); IR: νmax 3369, 3060, 1678,
1458, 1319, 1214, 1029, 747 cm−1; 1H NMR (400 MHz, CDCl3) δ 7.90
(dd, J = 8.0, 1.6 Hz, 2H), 7.88 (s, 1H), 7.51 (t, J = 7.2 Hz, 1H), 7.40
(t, J = 8.0 Hz, 2H), 7.33 (d, J = 6.8 Hz, 2H), 7.25–7.21 (m, 2H),
7.16–7.11 (m, 2H), 6.91 (d, J = 2.0 Hz, 1H), 6.82 (d, J = 2.4 Hz, 1H),
6.77 (dd, J = 8.4, 2.4 Hz, 1H), 5.00 (t, J = 7.2 Hz, 1H), 3.78 (dd,
J = 16.4, 6.8 Hz, 1H), 3.72–3.66 (m, 4H).
4-(2-Methyl-1H-indol-3-yl)octan-2-one (3l): Yellow solid; m.p. 42–
43 °C; IR: νmax 3353, 3052, 2926, 2857, 1705, 1461, 1360, 743 cm−1;
1H NMR (400 MHz, CDCl3) δ 7.74 (s, 1H), 7.56 (d, J = 7.6 Hz, 1H),
7.21 (d, J = 7.6 Hz, 1H), 7.08–7.00 (m, 2H), 3.38–3.30 (m, 1H), 3.03
(dd, J = 15.6, 8.4 Hz, 1H), 2.80 (dd, J = 16.0, 6.0 Hz, 1H), 2.36 (s,
3H), 1.93 (s, 3H), 1.89–1.81 (m, 1H), 1.73–1.67 (m, 1H), 1.29–1.07
(m, 4H), 0.79 (t, J = 7.2 Hz, 3H) ; MS (ESI): m/z 296 [M + K]+;
HRMS-ESI: calcd for C17H23NNaO: 280.1672; found: 280.1681.
4-(5-Nitro-1H-indol-3-yl)butan-2-one (3n): Yellow solid; m.p. 126–
127 °C, (lit.20 123–124 °C); IR: νmax 3301, 2917, 1696, 1472, 1327,
739 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J = 1.6 Hz, 2H), 8.08
(dd, J = 8.8, 2.0 Hz, 1H), 7.36 (d, J = 7.2 Hz, 1H), 7.14 (s, 1H), 3.07
(t, J = 7.2 Hz, 2H), 2.87 (t, J = 7.2 Hz, 2H), 2.17 (s, 3H).
3-(5-Methoxy-1H-indol-3-yl)-1-phenyl-3-(p-tolyl)propan-1-one
(3g): White solid; m.p. 134–137 °C; IR: νmax 3425, 3056, 1683, 1449,

JOURNAL OF CHEMICAL RESEARCH 2013 479
4-(1H-Indol-3-yl)butan-2-one (3o): White solid; m.p. 92–93 °C,
(lit.21 92–93 °C); IR: νmax 3322, 3064, 2921, 1701, 1458, 1351,
Hexasulfonato-hexakis(octyloxy)calix[6]arene (4d): 1H NMR (400
MHz, D2O/ DMSO-d6) δ 7.42 (s, 12H), 4.67 (br, 12H), 3.76 (br, 12H),
1.80 (br, 10H), 1.30 (br, 62H), 0.88 (br, 18H).
1
739 cm−1; H NMR (400 MHz, CDCl3) δ 7.97 (s, 1H), 7.57 (d, J =
7.6 Hz, 1H), 7.31 (d, J = 8.0 Hz, 1H), 7.17 (t, J = 6.8 Hz, 1H), 7.10 (t,
J = 6.8 Hz, 1H), 6.95 (d, J = 2.4 Hz, 1H), 3.04 (t, J = 7.2 Hz, 2H), 2.83
(t, J = 7.2 Hz, 2H), 2.13 (s, 3H).
We are grateful to the National Natural Science Foundation of
China (No. 200906083) and Natural Science Foundation of
Zhejiang Province (No. Y40900488) for financial support.
4-(1H-Indol-3-yl)octan-2-one (3p):Yellow oil; IR: νmax 3419, 3048,
1
2928, 1709, 1457, 1336, 741 cm−1; H NMR (400 MHz, CDCl3) δ
8.01 (s, 1H), 7.62 (d, J = 7.6 Hz, 1H), 7.30 (d, J = 8.0 Hz, 1H), 7.15 (t,
J = 7.6, 1H), 7.08 (t, J = 7.6 Hz, 1H), 6.91 (s, 1H), 3.44 (t, J = 6.0 Hz,
1H), 2.88 (dd, J = 16.0, 7.6 Hz, 1H), 2.78 (dd, J = 16.0, 6.4 Hz, 1H),
2.00 (s, 3H), 1.75–1.69 (m, 2H), 1.26–1.23 (m, 4H), 0.81 (t, J =
6.8 Hz, 3H); MS (ESI): m/z 282 [M + K]+.
Received 10 April 2013; accepted 3 June 2013
Paper 1301887 doi: 10.3184/174751913X13734725288804
Published online: 9 August 2013
4-(5-Methoxy-1H-indol-3-yl)butan-2-one (3q): White solid; m.p.
110–111 °C, (lit.6 107–108 °C); IR: νmax 3365, 3003, 1703, 1453, 1212
cm−1; 1H NMR (400 MHz, CDCl3) δ 7.90 (s, 1H), 7.21 (d, J = 8.8 Hz,
1H), 7.00 (d, J = 2.4 Hz, 1H), 6.93 (s, 1H), 6.83 (dd, J = 8.8, 2.4 Hz,
1H), 3.86 (s, 3H), 3.00 (t, J = 7.2 Hz, 2H), 2.83 (t, J = 7.6 Hz, 2H),
2.15 (s, 3H); MS (ESI): m/z 256 [M + K]+.
References
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2
3
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R.J. Sundberg, Indoles. Academic Press, San Diego, 1996.
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4-(5-Methoxy-1H-indol-3-yl)octan-2-one (3r): Yellow oil; IR: νmax
3410, 3031, 2929, 1708, 1456, 1216, 797 cm−1; 1H NMR (400 MHz,
CDCl3) δ 7.91 (s, 1H), 7.21 (d, J = 8.4 Hz, 1H), 7.06 (d, J = 2.4 Hz,
1H), 6.91 (d, J = 2.0 Hz, 1H), 6.83 (dd, J = 8.8, 2.4 Hz, 1H), 3.86 (s,
3H), 3.41 (dt, J = 14.0, 6.8 Hz, 1H), 2.85 (dd, J = 16.0, 7.6 Hz, 1H),
2.77 (dd, J = 16.0, 7.2 Hz, 1H), 2.02 (s, 3H), 1.78–1.63 (m, 2H), 1.31–
1.18 (m, 4H), 0.82 (t, J = 6.8 Hz, 3H); 13C NMR (101 MHz, CDCl3)
δ 208.8, 153.4, 131.6, 126.4, 121.9, 118.5, 111.8, 111.5, 101.3, 56.0,
50.1, 35.5, 32.7, 30.5, 29.8, 22.7, 14.1; MS (ESI): m/z 296 [M + Na]+;
HRMS-ESI: calcd for C17H23NNaO2: 296.1621; found: 296.1627.
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Hexasulfonato-hexakis(hydroxy)calix[6]arene (4a): H NMR (400
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MHz, D2O) δ 7.34 (s, 12H), 3.83 (s, 12H).
Hexasulfonato-hexakis(methyloxy)calix[6]arene (4b): 1H NMR
(400 MHz, D2O) δ 7.33 (s, 12H), 3.94 (s, 12H), 3.21 (s, 18H).
Hexasulfonato-hexakis(butyloxy)calix[6]arene (4c): 1H NMR (400
MHz, D2O) δ 7.45 (s, 12H), 3.88 (br, 1H), 3.30 (br, 12H), 1.28 (br,
10H), 1.05 (br, 14H), 0.51 (br, 18H).

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