Room-temperature synthesis of diindolylmethanes using silica-supported sulfuric acid as a reusable catalyst under solvent-free conditions

Article abstract of DOI:10.1080/00397911.2010.505696

Efficient electrophilic substitution reactions of indoles with various aromatic and aliphatic aldehydes were carried out using a catalytic amount of H₂SO₄SiO₂ under solvent-free conditions to afford the corresponding bis(indolyl)methanes in excellent yields.

Full text of DOI:10.1080/00397911.2010.505696

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Room-Temperature Synthesis of
Diindolylmethanes Using Silica-
Supported Sulfuric Acid as a Reusable
Catalyst Under Solvent-Free Conditions
Yan Zhang a , Xiang Chen a , Jun Liang a & Zhi-cai Shang a
a Department of Chemistry, Zhejiang University, Hangzhou, China
Available online: 14 Jun 2011
To cite this article: Yan Zhang, Xiang Chen, Jun Liang & Zhi-cai Shang (2011): Room-Temperature
Synthesis of Diindolylmethanes Using Silica-Supported Sulfuric Acid as a Reusable Catalyst
Under Solvent-Free Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 41:16, 2446-2454
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Synthetic Communications1, 41: 2446–2454, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2010.505696
ROOM-TEMPERATURE SYNTHESIS OF
DIINDOLYLMETHANES USING SILICA-SUPPORTED
SULFURIC ACID AS A REUSABLE CATALYST UNDER
SOLVENT-FREE CONDITIONS
Yan Zhang, Xiang Chen, Jun Liang, and Zhi-cai Shang
Department of Chemistry, Zhejiang University, Hangzhou, China
GRAPHICAL ABSTRACT
Abstract Efficient electrophilic substitution reactions of indoles with various aromatic and
aliphatic aldehydes were carried out using a catalytic amount of H2SO4 ꢀ SiO2 under
solvent-free conditions to afford the corresponding bis(indolyl)methanes in excellent yields.
Keywords Aldehydes; H2SO4 ꢀ SiO2; indole; solvent-free
INTRODUCTION
Recently, synthetic chemists have been very interested in developing highly
efficient transformations for the preparation of organic compounds. One of the main
themes of contemporary synthetic organic chemistry is the use of environmentally
feasible reagents, particularly in solvent-free conditions, and environmentally benign
catalytic systems, which are also required to be efficient and economic. Solvent-free
organic reactions are usually rapid, occur in good yields, and have environmental
and economic advantages. In addition, if these reactions can be performed using reu-
sable catalysts, they become more attractive. In this context, organic reactions under
solvent-free conditions at room temperature have achieved.
Actually, indole and their derivatives have been identified as an important class
of heterocyclic compounds in medicinal chemistry. In past decade, a number of
Received August 5, 2009.
Address correspondence to Zhi-cai Shang, Department of Chemistry, Zhejiang University, Zheda
Road, No. 38, Hangzhou 310027, China. E-mail: shangzc@zju.edu.cn
2446

REUSABLE H2SO4 ꢀ SiO2 CATALYST
2447
natural products containing bis(indolyl)methanes or bis(indoly)ethanes have been
isolated from marine sources.[1] Therefore, there is a great deal of interest in the syn-
thesis of this class of compounds. A number of synthetic methods for preparation of
these compounds have been reported in the literature by reaction of indole with various
aldehydes in the presence of catalysts such as H3PMo12O40,[2] NaBArF4 ,[3] La(NO3)3 ꢀ
6H2O,[4] Fe(DS)3,[5] HClO4,[6] ZrOCl2 ꢀ 8H2O,[7] BiOClO4 ꢀ xH2O,[8] ZrO2,[9] ZnO,[10]
and Lewis acids in ionic liquids.[11] However, most of these methods suffer from various
disadvantages such as long reaction times,[12] higher temperatures,[13] use of expensive
Lewis acids[14] or toxic solvent.[15] Here, we are lucky to find that silica-supported sul-
furic acid (H2SO4 ꢀ SiO2) is an efficient and recyclable catalyst for this reaction at room
temperature. To the best of our knowledge, few reports have been published for the
synthesis of indole derivatives under solvent-free conditions.[16,17]
RESULTS AND DISCUSSION
H2SO4 ꢀ SiO2 can easily be prepared from readily available silica gel and
H2SO4, which is very cheap and stable. We herein report the use of H2SO4 ꢀ SiO2
as catalyst in the electrophilic substituted indole reaction with a variety of aldehydes
under solvent-free conditions to afford bis(indolyl)methanes at room temperature
with excellent yields (Scheme 1, Table 1). Further, the H2SO4 ꢀ SiO2 has been reused
without loss of its activity simply by filtering the catalyst, washing with acetone, and
drying under vacuum.
It can be seen from Table 1 that regardless of whether the aromatic substituent
R2 of 2 is electron withdrawing or electron donating, the catalyst efficiently pro-
moted the reaction with good yields. Also, the aliphatic aldehydes react with much
better results.
The possibility of recycling the catalyst was examined. For this reason, the
reaction of aldehyde with indol under solvent-free conditions at room temperature
in the presence of H2SO4 ꢀ SiO2 was studied (Table 2). After completion of the
reaction, the catalyst was recovered by simple filtration and reused in subsequent
reactions with consistent activity.
In summary, we have developed an environmentally friendly, economical, and
efficient synthetic protocol for bis(indolyl)methanes using H2SO4 ꢀ SiO2 under
solvent-free conditions at room temperature. The short reaction procedure and
Scheme 1.

2448
Y. ZHANG ET AL.
Table 1. The reaction of aldehyde with indol under solvent-free conditions at room temperature
Entry
1
Aldehydes
Indole
1a
Product
Time (min)
3
Yield (%)a
91
3a
2
1a
3b
5
88
3
4
5
6
7
1a
1b
1a
1b
1a
3c
3d
3e
3f
8
8
87
93
86
90
84
9
9
3g
10
8
9
1a
1b
3h
3i
8
8
88
94
10
11
1a
1a
3j
4
3
94
91
3k
12
1a
3l
8
90
13
14
1a
1b
3m
3n
6
6
92
94
15
16
1a
1b
3o
3p
11
11
85
92
17
18
1a
1b
3q
3r
10
10
84
90
(Continued )

REUSABLE H2SO4 ꢀ SiO2 CATALYST
Table 1. Continued
2449
Entry
Aldehydes
Indole
Product
Time (min)
Yield (%)a
19
20
1a
1b
3s
3t
10
10
86
89
21
1a
3u
11
82
22
23
24
1a
1a
1a
3v
3w
3x
9
2
2
87
90
88
aIsolated yields after column chromatography.
a
Table 2. Recycle experiment of H2SO4 ꢀ SiO2
Run
Time
Yield (%)b
1
2
3
8
8
8
88
85
84
aReactions performed with 1.0 mmol of 4-nitrobenzaldehyde, 2 mmol of indole, and
50 mg of H2SO4 ꢀ SiO2 mixed for 8 min under solvent-free conditions at room temperature.
bIsolated yields after purification.
reusability of the catalyst make this method one of the most efficient methods for the
synthesis of this class of compounds.
EXPERIMENTAL
General Considerations
H2SO4 ꢀ SiO2 was prepared by the reported methed.[18] All the reagents were
obtained from commercial sources. Melting points were recorded on an Electrothermal

2450
Y. ZHANG ET AL.
digital microscopic melting-point apparatus and are uncorrected. The progress of
1
reactions was monitored by thin-layer chromatography (TLC) on silica. H NMR
and 13C NMR spectra were recorded with tetramethylsilane (TMS) as internal stan-
dard using a Bruker AMX 500-MHz spectrometer at 500 and 125 MHz in CDCl3 or
DMSO-d6 solution, respectively. Chemical shifts were measured in part per million
(ppm) and coupling constants (J) in hertz (Hz). Infrared (IR) spectra were measured
with a Nicolet Nexus Fourier transform (FT)–IR 670 spectrophotometer.
Low-resolution mass spectrographic (MS) analyses were measured on a Bruke
Esquire 3000 spectrometer using the ESI (electrospray ionization) technique.
General Procedure for the Synthesis of Diindolylmethanes
A mixture of aldehyde (1 mmol), indole (2 mmol), and H2SO4 ꢀ SiO2 (50 mg)
were ground together in a mortar with a pestle at room temperature for several min-
utes. After completion of the reaction, as indicated by TLC, the reaction mixture was
diluted with MeOH (5 mL ꢁ 2) or ethyl acetate (5 mL ꢁ 2). The liquid was filtered
off, and the catalyst was washed with acetone (5 mL). Then the organic layer was
concentrated under reduced pressure to afford the crude product, which was then
purified by column chromatography and eluted with ethyl acetate and petroleum
ether mixture.
Data
Compound 3a. Solid; mp 140–142 ꢂC; IR (KBr), nmax: 700, 746, 1093, 1455,
1
1492, 1575, 1600, 3055 and 3407 cmꢃ1; H NMR (500 MHz, DMSO-d6): d 5.91 (s,
1H), 6.91 (q, 4H), 7.08 (t, 2H), 7.19 (d, 1H, J ¼ 7.4 Hz), 7.29 (t, 2H), 7.36 (d, 2H,
J ¼ 8.0 Hz), 7.42 (d, 4H, J ¼ 8.1 Hz), 10.88 (s, 2H, NH).
Compound 3b. Solid; mp 210–212 ꢂC; IR (KBr), nmax: 744, 795, 1010, 1456,
1
1510, 1597, 1612, 3054 and 3407 cmꢃ1; H NMR (500 MHz, DMSO-d6): d 5.74 (s,
1H), 6.69 (d, 2H, J ¼ 8.5 Hz), 6.81 (d, 2H, J ¼ 1.8 Hz), 6.87 (t, 2H), 7.04 (t, 2H),
7.17 (d, 2H, J ¼ 8.4 Hz), 7.30 (d, 2H, J ¼ 7.9 Hz), 7.36 (d, 2H, J ¼ 8.1 Hz), 9.18 (s,
1H), 10.78 (s, 2H, NH).
Compound 3c. Solid; mp 93–95 ꢂC; IR (KBr), nmax: 743, 777, 1010, 1092,
1
1417, 1456, 1510, 1618, 3051, and 3411 cmꢃ1; H NMR (500 MHz, DMSO-d6): d
2.28 (s, 3H), 5.87 (s, 1H), 6.90 (m, 4H), 7.08 (m, 4H),7.31 (d, 2H, J ¼ 8.0 Hz), 7.36
(d, 2H, J ¼ 8.0 Hz),7.42 (d, 2H, J ¼ 8.2 Hz), 10.86 (s, 2H, NH).
1
Compound 3d. Solid; mp 198–200 ꢂC; H NMR (500 MHz, CDCl3): d 2.46
(s, 3H), 3.75 (s, 6H), 6.0 (s, 1H), 6.67 (s, 2H), 7.13 (m, 2H), 7.22 (d, 2H, J ¼ 7.8 Hz),
7.33 (m, 2H), 7.39 (m, 4H), 7.54 (d, 2H, J ¼ 7.9 Hz).
Compound 3e. Solid; mp 194–196 ꢂC; IR (KBr), nmax: 741, 784, 1031, 1245,
1
1419, 1455, 1509, 1610, 3055, and 3397 cmꢃ1; H NMR (500 MHz, DMSO): d 3.70
(s, 3H), 5.80 (s, 1H), 6.85 (m, 6H), 7.05 (m, 2H), 7.29 (m, 4H), 7.37 (d, 2H,
J ¼ 8.1 Hz), 10.81 (s, 2H, NH).

REUSABLE H2SO4 ꢀ SiO2 CATALYST
2451
Compound 3f. Solid; mp 220–222 ꢂC; IR (KBr), nmax: 737, 806, 1029, 1248,
1
1463, 1509, 1611, 3043, and 3448 cmꢃ1; H NMR (500 MHz, CDCl3): d 3.72 (s,
6H), 3.85 (s, 3H), 5.92 (s, 1H), 6.60 (s, 2H), 6.90 (d, 2H, J ¼ 8.6 Hz), 7.08 (m, 2H),
7.27 (m, 2H), 7.36 (m, 4H), 7.47 (d, 2H, J ¼ 7.9 Hz).
1
Compound 3g. Solid; mp 204–206 ꢂC; H NMR (500 MHz, DMSO): d 2.83
(s, 6H), 5.69 (s, 1H), 6.64 (d, 2H, J ¼ 8.7 Hz), 6.78 (d, 2H, J ¼ 2.0 Hz), 6.82 (s,
2H), 7.02 (s, 2H), 7.15 (d, 2H, J ¼ 8.6 Hz), 7.27 (d, 2H, J ¼ 7.9 Hz), 7.33 (d, 2H,
J ¼ 8.1 Hz), 10.74 (s, 2H, NH).
1
Compound 3h. Solid; mp 245–247 ꢂC; H NMR (500 MHz, DMSO): d 6.03
(s, 1H), 6.89 (m, 4H), 7.05 (m, 2H), 7.29 (d, 2H, J¼ 8.0 Hz), 7.37 (d, 2H, J ¼ 8.1 Hz),
7.61 (d, 2H, J¼ 8.7 Hz), 8.15 (d, 2H, J ¼ 8.7 Hz), 10.93 (s, 2H, NH).
Compound 3i. Solid; mp 210–212 ꢂC; 1H NMR (500 MHz, CDCl3): d 3.75 (s,
6H), 6.05 (s, 1H), 6.62 (s, 2H), 7.08 (t, 2H, J ¼ 7.3 Hz), 7.29 (t, 2H, J ¼ 7.3 Hz), 7.39
(t, 4H, J ¼ 8.6 Hz), 7.56 (d, 2H, J ¼ 8.6 Hz), 8.18 (d, 2H, J ¼ 8.6 Hz).
Compound 3j. Solid; mp 154–156 ꢂC; IR (KBr), nmax: 741, 1088, 1335, 1419,
1456, 1558, 1612, 3057, and 3411 cmꢃ1; 1H NMR (500 MHz, DMSO): d 6.26 (s, 1H),
6.78 (s, 2H), 6.91 (m, 2H), 7.08 (m, 2H), 7.14 (m, 1H), 7.24 (m, 1H), 7.30 (m, 3H),
7.41 (d, 2H, J ¼ 8.1 Hz), 7.65 (d, 2H, J ¼ 8.0 Hz), 10.91 (s, 2H, NH); 13C NMR
(125 MHz, DMSO): 39.7, 112.0, 117.2, 118.9, 119.2, 121.5, 124.4, 124.5, 127.0,
127.9, 128.4, 130.8, 133.0, 137.1, 143.9; MS (ESI) m=z 401.3 ([M þ H])þ.
Compound 3k. Solid; mp 259–261 ꢂC; IR (KBr), nmax: 745, 1092, 1338, 1456,
1486, 1592, 1702, 3055 and 3411 cmꢃ1; 1H NMR (500 MHz, DMSO): d 6.17 (s, 1H),
6.65 (s, 1H), 6.72 (s, 2H), 6.84 (m, 3H), 7.02 (m, 6H), 7.26 (d, 3H, J ¼ 7.8 Hz), 7.33
(d, 2H, J ¼ 8.2 Hz), 9.35 (s, 1H), 10.71 (s, 2H, NH).
Compound 3l. Solid; mp 138–140 ꢂC; IR (KBr), nmax: 744, 821, 1100, 1416,
1
1456, 1483, 1618, 3056, and 3412 cmꢃ1; H NMR (500 MHz, CDCl3): d 5.93 (s,
1H), 6.56 (d, 2H, J ¼ 1.7 Hz), 6.67 (d, 1H, J ¼ 8.5 Hz), 7.00 (m, 2H), 7.16 (m, 2H),
7.22 (m, 1H), 7.27 (m, 3H), 7.35 (d, 2H, J ¼ 7.9 Hz), 7.85 (s, 2H, NH). 13C NMR
(125 MHz, CDCl3): 35.6, 111.6, 113.1, 116.7, 118.6, 119.9, 122.6, 123.9, 126.8,
131.0, 131.8, 132.6, 137.0, 153.8; MS (ESI) m=z 417.3 ([M þ H])þ.
1
Compound 3m. Solid; H NMR (500 MHz, CDCl3): d 6.06 (s, 1H), 6.15 (s,
1H, OH), 6.61 (d, 2H, J ¼ 1.8 Hz), 6.79 (d, 1H, J ¼ 8.5 Hz), 7.04 (m, 2H), 7.12 (m,
1H), 7.16 (d, 1H, J ¼ 2.6 Hz), 7.20 (m, 2H), 7.31 (d, 2H, J ¼ 8 Hz), 7.41 (d, 2H,
J ¼ 7.9 Hz), 8.11 (s, 2H, NH).
Compound 3n. Solid; mp 240–242 ꢂC; IR (KBr), nmax: 743, 1107, 1370, 1412,
1483, 1544, 1613, 3055 and 3477 cmꢃ1; 1H NMR (500 MHz, DMSO): d 3.70 (s, 6H),
6.16 (s, 1H), 6.79 (s, 2H), 6.87 (d, 1H, J ¼ 8.6 Hz), 6.92 (m, 2H), 6.97 (d, 1H,
J ¼ 2.6 Hz), 7.05 (m, 1H), 7.11 (m, 2H), 7.27 (d, 2H, J ¼ 7.9 Hz), 7.37 (d, 2H,
J ¼ 8.2 Hz), 9.78 (s, 1H); 13C NMR (125 MHz, DMSO): 31.9, 32.7, 110.1, 117.0,
117.2, 118.8, 119.4, 121.6, 122.7, 127.0, 127.4, 128.4, 129.0, 133.6, 137.5, 153.7;
MS (ESI) m=z 401.4 ([M þ H])þ, 399.4 ([M ꢃ H])ꢃ.

2452
Y. ZHANG ET AL.
Compound 3o. Solid; mp 144–146 ꢂC; IR (KBr), nmax: 745, 1011, 1337, 1491,
1
1521, 1589, 1617 and 3409 cmꢃ1; H NMR (500 MHz, CDCl3): d 6.12 (s, 1H), 6.69
(d, 2H, J ¼ 1.6 Hz), 6.90 (d, 1H, J ¼ 8.9 Hz), 7.02 (m, 2H), 7.19 (m, 2H), 7.36 (m,
4H), 8.04 (m, 2H), 8.11 (s, 2H); 13C NMR (125 MHz, CDCl3): 35.3, 111.7, 116.4,
116.9, 119.7, 120.0, 122.9, 123.9, 124.6, 126.3, 126.7, 130.6, 137.2, 141.8, 160.6,
171.7; MS (ESI) m=z 382.4 ([M ꢃ H])ꢃ.
Compound 3p. Solid; mp 251–253 ꢂC; IR (KBr), nmax: 749, 1274, 1340, 1371,
1483, 1515, 1587, 1641 and 3474 cmꢃ1; 1H NMR (500 MHz, DMSO): d 3.70 (s, 6H),
6.20 (s, 1H), 6.83 (s, 2H), 6.91 (m, 2H), 7.06 (d, 1H, J ¼ 8.9 Hz), 7.12 (m, 2H),7.27 (d,
2H, J ¼ 7.9 Hz), 7.38 (d, 2H, J ¼ 8.2 Hz), 7.90 (d, 1H, J ¼ 2.8 Hz), 8.01 (m, 1H), 11.2
(s, 1H); 13C NMR (125 MHz, DMSO): 32.0, 32.8, 110.2, 115.9, 116.4, 119.0, 119.3,
121.7, 124.2, 125.3, 127.3, 128.6, 132.7, 137.6, 140.0, 161.6; MS (ESI) m=z 410.4
([M ꢃ H])ꢃ.
Compound 3q. Solid; mp 225–227 ꢂC; IR (KBr), nmax: 744, 1010, 1272, 1440,
1456, 1477, 1616, 3053 and 3411 cmꢃ1; 1H NMR (500 MHz, DMSO): d 3.85 (s, 3H),
6.53 (s, 1H), 6.77 (m, 1H), 6.83 (d, 1H, J ¼ 7.9 Hz), 6.97 (m, 5H), 7.18 (m, 2H), 7.54
(m, 4H), 8.70 (s, 1H), 10.84 (s, 2H); 13C NMR (125 MHz, CDCl3): 32.98, 56.13,
108.8, 111.3, 118.8, 119.3, 119.4, 120.1, 121.9, 122.3, 123.8, 127.3, 130.0, 136.9,
143.3, 146.6; MS (ESI) m=z 367.3 ([M ꢃ H])ꢃ.
Compound 3r. Solid; mp 244–246 ꢂC; IR (KBr),nmax: 742, 1068, 1269, 1371,
1440, 1475, 1591, 1616, 3049 and 3542 cmꢃ1; 1H NMR (500 MHz, DMSO): d 3.67 (s,
6H), 3.80 (s, 3H), 6.23 (s, 1H), 6.63 (t, 1H, J ¼ 7.9 Hz), 6.71 (m, 1H), 6.76 (m, 2H),
6.78 (d, 1H, J ¼ 1.4 Hz), 6.91 (m, 2H), 7.11 (m, 2H), 7.29 (d, 2H, J ¼ 7.9 Hz), 7.35 (d,
2H, J ¼ 8.2 Hz), 8.55 (s, 1H); 13C NMR (125 MHz, DMSO): 31.7, 32.7, 56.2, 109.6,
110.0, 117.8, 118.6, 118.7, 119.6, 121.4, 121.8, 127.6, 128.3, 131.6, 137.4, 143.6, 147.7;
MS (ESI) m=z 395.4 ([M ꢃ H])ꢃ.
Compound 3s. Solid; mp 125–127 ꢂC; IR (KBr), nmax: 745, 1094, 1457, 1474,
1
1597, 1618, 1686, 3055 and 3410 cmꢃ1; H NMR (500 MHz, CDCl3): d 5.75 (s, 1H,
OH), 6.14 (s, 1H), 6.31 (s, 1H, OH), 6.55 (d, 2H, J ¼ 1.5 Hz), 6.85 (m, 3H), 7.06 (t,
2H, J ¼ 7.3 Hz), 7.23 (m, 4H), 7.48 (d, 2H, J ¼ 7.9 Hz), 7.92 (s, 2H, NH).
Compound 3t. Solid; mp 221–223 ꢂC; IR (KBr), nmax: 736, 1371, 1474, 1597,
1
1617, 1701, 3052 and 3487 cmꢃ1; H NMR (500 MHz, DMSO): d 3.66 (s, 6H), 6.29
(s, 1H), 6.54 (t, 1H, J ¼ 7.8 Hz), 6.64 (t, 1H, J ¼ 1.0 Hz), 6.70 (m, 1H), 6.77 (s, 2H),
6.93 (t, 2H, J ¼ 7.7 Hz), 7.12 (t, 3H, J ¼ 7.5 Hz), 7.36 (t, 3H, J ¼ 6.6 Hz), 8.30 (s, 1H),
9.29 (s, 1H); 13C NMR (125 MHz, DMSO): 31.9, 32.7, 110.0, 113.4, 118.1, 118.7,
118.8, 119.7, 120.5, 121.5, 127.8, 128.3, 132.0, 137.5, 143.0, 145.3; MS (ESI) m=z
381.4 ([M ꢃ H])ꢃ.
Compound 3u. Solid; mp 200–202 ꢂC; IR (KBr), nmax: 744, 827, 1095, 1456,
1
1518, 1600, 1620, 3056 and 3408 cmꢃ1; H NMR (500 MHz, DMSO): d 6.83 (t, 4H,
J ¼ 7.6 Hz), 6.90 (s, 1H), 7.02 (t, 2H, J ¼ 7.3 Hz), 7.12 (s, 2H), 7.32 (m, 5H), 7.70 (t,
2H, J ¼ 7.2 Hz), 8.34 (m, 1H), 9.80 (s, 1H), 10.71 (s, 2H, NH).
Compound 3v. Solid; mp 144–146 ꢂC; IR (KBr), nmax: 742, 782, 1010, 1456,
1503, 1617, 1719, 3054 and 3410 cmꢃ1; 1H NMR (500 MHz, DMSO): d 5.92 (s, 1H),

REUSABLE H2SO4 ꢀ SiO2 CATALYST
2453
6.12 (d, 1H, J ¼ 3.0 Hz), 6.37 (m, 1H), 6.91 (t, 2H, J ¼ 7.2 Hz), 7.06 (m, 4H),7.37 (d,
2H, J ¼ 8.1 Hz), 7.43 (d, 2H, J ¼ 7.9 Hz), 7.54 (d, 1H, J ¼ 0.8 Hz); MS (ESI) m=z
311.1 ([M ꢃ H])ꢃ.
1
Compound 3w. Solid; mp 78–80 ꢂC; H NMR (500 MHz, DMSO): d 1.0 (d,
6H, J ¼ 6.5 Hz), 2.75 (m, 1H), 4.20 (d, 1H, J ¼ 9.2 Hz), 6.95 (m, 2H), 7.04 (m, 2H),
7.35 (t, 4H, J ¼ 4.4 Hz), 7.67 (d, 2H, J ¼ 7.9 Hz), 10.8 (s, 1H).
1
Compound 3x. Solid; H NMR (500 MHz, DMSO): d 4.16 (s, 2H), 6.94 (m,
2H), 7.05 (m, 2H), 7.15 (d, 2H, J ¼ 2.0 Hz), 7.35 (d, 2H, J ¼ 8.0 Hz), 7.55 (d, 2H,
J ¼ 7.9 Hz), 10.75 (s, 2H, NH).
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