PAPER
1949
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes Catalyzed by Zirconium Tetrachloride AnEf icentandPracticalProces fortheSynthesi ofBis(indoly)methanes Zhang, Liang Yin, Yong-Mei Wang* Zhan-Hui Department of Chemistry and the State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, P. R. China Fax +86(22)23502654; E-mail:
[email protected] Received 24 December 2004; revised 10 March 2005
Abstract: Zirconium tetrachloride is used as a catalyst for the electrophilic substitution reaction of indole with aldehydes or ketones at ambient temperature to afford the corresponding bis(indolyl)methanes in good to excellent yields. Key words: indole, aldehydes, ketones, bis(indolyl)methanes, electrophilic substitution, zirconium tetrachloride
Indole and its derivatives are important intermediates in organic synthesis and exhibit various physiological properties and pharmacological activities.1 Over the past decade, a number of natural products containing bis(indolyl)methanes or bis(indolyl)ethanes have been isolated from marine sources.2 Bis(indolyl)methanes are found in cruciferous plants and are known to promote beneficial estrogen metabolism3 and induce apoptosis in human cancer cell. Therefore the preparation of these intermediates has received increased attention from synthetic organic chemists and biologists. The reaction of indole with aldehydes or ketones produces azafulvenium salts, which then undergo further addition with the second indole molecule to afford bis(indolyl)ethanes.4 Generally, this reaction is promoted using protic acids,5 Lewis acids (such as zinc chloride, indium chloride, indium triflate, dysprosium triflate, lanthanide triflate, lithium perchlorate, ferric chloride,6 or heteropolyacid7), and heterogeneous catalysts (zeolites, clay, and supported reagents8). Other catalysts such as iodine,9 NBS,10 potassium hydrogen sulfate,11 triphenyl phosphonium perchlorate,12 CAN,13 and hexamethylenetetraamine-bromine14 have also been used to catalyze this reaction. This reaction also proceeds in ionic liquids such as 1-butyl-3-methylimidazolium tetrafluoroborate or 1-butyl-3-methylimidazolium hexafluorophosphate15 or in the solid-state by employing a highpressure mercury lamp.16 Recently, rare-earth perfluoroocanoates [RE(PFO)3],17 trichloro-1,3,5-triazine,18 and ionic liquids in conjunction with In(OTf)3 or FeCl3·6H2O19 were employed for this transformation. Although these methods are suitable for certain syntheses, there sometimes exist some drawbacks such as long reaction time (e.g. 10 days5a), expensive reagents (e.g. dysprosium triflate6d), low yields of products in some cases, high catalyst loading, corrosive reagents, and large amounts of solid supports, which would eventually result in the genSYNTHESIS 2005, No. 12, pp 1949–1954xx. 205 Advanced online publication: 24.06.2005 DOI: 10.1055/s-2005-869959; Art ID: F18804SS © Georg Thieme Verlag Stuttgart · New York
eration of a large amount of toxic waste. For this reason, superior catalysts, which are cheap, less toxic, easily available, air-stable, and water-tolerant, are desirable. In recent years, zirconium tetrachloride has been explored extensively in organic reactions.20 Industrially its applications are steadily increasing.21 Furthermore, the high abundance of zirconium(IV) compounds in the earth’s crust make them less costly and easily available as well as this they also display low toxicity.22 In particular, zirconium tetrachloride has been found to be a more effective catalyst than conventional Lewis acids in promoting various transformations including the synthesis of nitriles,23 Biginelli reaction,24 the synthesis of chloromethyl esters,25 selective deprotection of tert-butyldimethylsilyl ethers,26 cleavage of prenyl ethers and para-methoxybenzyl ethers,27 one-pot conversion of tert-butyldimethylsilyl ethers and tetrahydropyranyl ethers to the corresponding acetates,28 nucleophilic-opening of epoxides,29 conversion of aldehydes to geminal-diacetates and dipivalates,30 the deprenylation of ethers and esters,31 the iodination of alcohols,32 selective tosylation of alcohols,33 Boc-protection of amines,34 cyclization of ortho-allylphenols,35 conversion of epoxides into b-chlorohydrins,36 and the preparation of MOM ether.37 In continuation of our interest in the use of Lewis acids as efficient catalysts in various transformations,38 we herein report the synthesis of bis(indolyl)methanes from indole and carbonyl compounds in the presence of a catalytic amount of zirconium tetrachloride (5 mol%) at room temperature (Scheme 1). R1 ZrCl4
O N 1
H
+ R1
R2 2
R2
CH3CN, r.t.
N H
N 3
H
Scheme 1
Initially, we carried out the reaction of indole with benzaldehyde in the presence of 5 mol% of zirconium tetrachloride in different anhydrous solvents at room temperature. The results are shown in Table 1. Among the solvents examined, acetonitrile proved to be the most effective. Similar results were observed in dichloromenthane, but with longer reaction times, however, utilizing other solvents proved to be quite unsatisfactory.
1950
PAPER
Z.-H. Zhang et al.
Table 1 Effect of Solvent on the Conversion of Indole and Benzaldehyde to Phenyl-3,3¢-diindoylmenthanea Time (h)
Yield (%)b
Entry
Solvent
1
CH3CN
0.5
96
2
CH3COOC2H5
1
86
3
CH2Cl2
1
92
4
CH3OH
4
80
5
C2H5OH
4
76
6
THF
20
84
7
DMF
25
42
a
All reactions were carried out using a catalytic amount of ZrCl4 (5.0 mol% based on the amount of indole) at r.t. b Isolated yields.
Next, we carried out the zirconium tetrachloride catalyzed electrophilic substitution reaction of indole with a variety of aldehydes or ketones to better understand both the scope and the generality of this method (Table 2). As shown in Table 2, a series of aromatic, aliphatic and heterocyclic aldehydes underwent electrophilic substitution reaction with indole smoothly to afford a wide range of substituted bis(indolyl)methanes in good to excellent yields. Many of the pharmacologically relevant substitution patterns on the aromatic ring could be introduced with high efficiency by using this procedure. The electron deficiency and the nature of the substituents on the aromatic ring affect the conversion rate; aromatic aldehydes Table 2
The reaction conditions are mild enough not to induce any isomerization of conjugated aldehydes (2z) and damage to moieties such as methoxy (2n, 2o, and 2t), methylenedioxy (2p), and allyloxy (2w), which often undergo cleavage under strong acidic reaction conditions. In the absence of zirconium tetrachloride, the reaction did not yield any product at room temperature even after a long reaction time. The efficacy of various Lewis acids was tested for this conversion, and the results are shown in Table 3. Among these catalysts, zirconium tetrachloride was found to be superior in terms of yield and reaction rate; a result of the mild Lewis acidity of the zirconium ion, which activates the carbonyl group to promote the reaction.
Zirconium Tetrachloride Catalyzed Synthesis of Bis(indolyl)methanes 2
Entry
having electron-withdrawing groups on the aromatic ring (i.e. NO2, F) react faster than benzaldehyde and an electron-donating substituent (i.e. CH3, OCH3, OH) deactivated aryl aldehydes remarkably. Furthermore, unsaturated aldehydes, such as cinnamaldehyde, gave the corresponding bis(indolyl)methanes without polymerization under the above reaction conditions. The heterocyclic aldehydes such as furfural and 2-thiophenecarboxaldehyde also worked well without the formation of any side products. 4-(Diethylamino)benzaldehyde (2ab), however, remained unaffected even when the reaction mixture was stirred at room temperature for one day; the starting material could be quantitatively recovered. This result may be due to the coordination of zirconium ion with the diethylamino group, which deactivates the catalyst. Ketones required longer reaction times, which is most probably due to the electron-donating and steric effects of the methyl group.
3 1
2
R
R
Time (min)
Yield (%)
1
Ph
H (2a)
30
2
2-NO2C6H4
H (2b)
3
3-NO2C6H4
4
Mp (°C) a
Recrystallization solvent Found
Reported
96
EtOAc–hexane
125–126
125–1278j
20
95
EtOH–CCl4
141–143
140–14216a
H (2c)
10
93
Et2O–EtOH
260–262
265–2668j
4-NO2C6H4
H (2d)
15
94
hexane
220–222
222–22813
5
2-ClC6H4
H (2e)
25
93
EtOAc–hexane
73–75
72–749a
6
3-ClC6H4
H (2f)
28
94
EtOAc–hexane
89–91
7
4-ClC6H4
H (2g)
25
96
MeOH–H2O
103–106
8
2,4-Cl2C6H3
H (2h)
20
95
EtOAc–hexane
103–105
9
3,4-Cl2C6H3
H (2i)
20
94
EtOAc–hexane
155–157
10
4-FC6H4
H (2j)
25
93
EtOAc–hexane
72–74
11
2-OH-5-ClC6H3
H (2k)
35
92
EtOAc–hexane
80–82
12
2-MeC6H4
H (2l)
45
94
EtOAc–hexane
100–102
13
4-MeC6H4
H (2m)
40
95
EtOAc–hexane
96–98
Synthesis 2005, No. 12, 1949–1954
© Thieme Stuttgart · New York
104–1058b
154–1566f
78–809a
95–976f
PAPER Table 2
1951
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes Zirconium Tetrachloride Catalyzed Synthesis of Bis(indolyl)methanes (continued) 2
3 1
2
Mp (°C) a
Entry
R
R
14
2-OMeC6H4
H (2n)
50
94
EtOAc–hexane
134–136
15
4-OMeC6H4
H (2o)
45
94
MeOH–H2O
190–193
191–1938j
16
3,4-(OCH2O)C6H3
H (2p)
60
90
EtOAc–hexane
102–104
97–996f
17
2-OHC6H4
H (2q)
120
91
benzene–hexane
342–344
3495a
18
3-OHC6H4
H (2r)
60
97
EtOAc–hexane
101–103
985a
19
4-OHC6H4
H (2s)
80
86
EtOAc–hexane
120–122
122–12413
20
3-MeO-4-OHC 6H3
H (2t)
45
95
EtOAc–hexane
102–103
99–1016c
21
CH3(CH2)4
H (2u)
80
90
EtOAc–hexane
67–69
68–706f
22
CH3(CH2)5
H (2v)
90
92
EtOAc–hexane
68–70
66–686h
23
CHO
50
95
EtOAc–hexane
153–155
30
90
benzene–hexane
320–322
32214
60
89
hexane
186–188
188–1908c
120
81
EtOAc–hexane
96–98
995a
45
94
EtOAc–hexane
236–239
2406f
24 h
–b
6h
89
EtOAc–hexane
165–167
167–16813
6h
92
EtOAc–hexane
116–118
118–1206f
Time (min)
Yield (%)
Recrystallization solvent Found
Reported
OCH2CH=CH2
(2w) 24 O
CHO
(2x) 25 S
CHO
(2y) 26
CHO
(2z) 27
CHO
28
(2aa) 4-Et2NC6H4
H (2ab)
29
CH3
CH3(2ac)
30 O
31
(2ad) Ph
CH3 (2ae)
6h
85
EtOH
188–190
190–19213
32
4-NO2C6H4
CH3 (2af)
6h
87
EtOAc–hexane
232–235
234–2366a
a b
Isolated yield after purification. No reaction.
This reaction was further explored for the synthesis of tetraindolyl compounds 6 and 7 by the condensation of terephthalaldehyde 4 and 2,2¢-di(formylphenoxy) propane 5 with four equivalents of indole under similar conditions in excellent yields (Scheme 2).
In conclusion, zirconium tetrachloride has been employed for the first time as a novel and efficient catalyst for the synthesis of bis(indolyl)methanes by the electrophilic substitution reaction of indole with aldehydes or ketones. This method is applicable to a wide range of aldehydes, including aromatic, aliphatic, a,b-unsaturated and hetero-
Synthesis 2005, No. 12, 1949–1954
© Thieme Stuttgart · New York
1952
PAPER
Z.-H. Zhang et al.
Table 3 Effect of Different Lewis Acids on the Reaction of Indole with Benzaldehydea Entry
Yield (%)b
Catalyst
Time (h)
1
None
10
0
2
BiCl3
5
87
3
Bi(NO3)5·5H2O
4
86
4
CuCl2
2
93
5
InCl3
6
91
6
InBr3
2
92
7 8
In(OTf)3
0.42 0.8
716c 78
9
CoCl2·6H2O
24
37
10
ZnCl2
24
11
11
ZnBr2
24
20
12
FeCl3
24
73
13
Cu(OTf)2
5
90
14
NiCl2·6H2O
24
trace
15
Mg(ClO4)2
24
46
16
Ga(ClO4)3
8
90
17
Pr(ClO4)3
8
92
18
LaCl3
15
8
19
LiBr
24
18
20
LiCl
24
16
21
SrCl2·6H2O
15
0
22
Ti(SO4)2
4
92
23
AlCl3
15
89
24
ZrO(NO3)2·2H2O
20
73
25
ZrSO4·4H2O
8
84
26
ZrOCl2·8H2O
20
62
27
Zr(NO3)5·5H2O
5
88
28
ZrCl4
0.5
96
Scheme 2
a
The reaction was carried out according to the typical experimental procedure. b Isolated yields.
cyclic substrates, and ketones. The attractive features of this procedure are the mild reaction conditions, high conversions, cleaner reaction profiles, inexpensive and environmentally friendly catalyst, all of which make it an attractive strategy for the preparation of bis(indolyl)methanes.
Synthesis 2005, No. 12, 1949–1954
© Thieme Stuttgart · New York
Melting points were recorded on X-4 apparatus and are uncorrected. IR spectra were recorded on a Bio-Rad FTS 135 spectrophotometer using KBr optics. NMR spectra were recorded with a Bruker spectrometer at 300 (1H NMR) and 75 (13C NMR) MHz using TMS as internal standard. Mass spectra were recorded on a VG-7070E mass spectrometer. Elemental analyses were performed on a Yanaca CDRDER MT-3 analyzer. Synthesis of Bis(indolyl)methanes 3; General Procedure A mixture of indole (2.0 mmol), aldehyde or ketone (1.0 mmol), and ZrCl4 (0.023 g, 0.1 mmol) in MeCN (5 mL) was stirred at r.t. for the appropriate time (Table 2). After completion of the reaction, as indicated by TLC, the mixture was quenched with H2O (5 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layer was separated and dried (Na2SO4), concentrated in vacuo, and the product was purified by column chromatography on silica gel (EtOAc–cyclohexane, 1:9) to give pure bis(indolyl)methanes. 3,3¢-Bisindolyl-3-chlorophenylmethane (3f) IR: 742, 1010, 1093, 1294, 1337, 1417, 1455, 1592, 2923, 3054, 3409 cm–1. 1
H NMR (300 MHz, CDCl3): d = 6.02 (s, 1 H), 6.57 (s, 2 H), 7.00 (t, J = 7.8 Hz, 2 H), 7.06–7.22 (m, 6 H), 7.36 (d, J = 7.8 Hz, 4 H), 7.90 (br s, 2 H, NH).
13
C NMR (75 MHz, CDCl3): d = 40.1, 111.3, 119.1, 119.6, 120.0, 122.3, 123.8, 126.6, 127.0, 129.0, 129.7, 134.2, 136.8, 146.3.
EIMS: m/z (%) = 358 [33, (M + 2)+], 356 (100, M+), 245 (24), 239 (6). Anal. Calcd for C23H17ClN2: C, 77.41; H, 4.80; N, 7.85. Found: C, 77.48; H, 4.85; N, 7.82. 3,3¢-Bisindolyl-2,4-dichlorophenylmethane (3h) IR: 739, 794, 864, 1096, 1456, 1586, 2848, 3055, 3405 cm–1. 1
H NMR (300 MHz, CDCl3): d = 6.27 (s, 1 H), 6.84 (s, 2 H), 7.03 (t, J = 7.8 Hz, 4 H), 7.37 (d, J = 7.8 Hz, 6 H), 7.45 (d, J = 2.1 Hz, 1 H), 7.95 (br s, 2 H, NH).
PAPER
An Efficient and Practical Process for the Synthesis of Bis(indolyl)methanes
13
C NMR (75 MHz, CDCl3): d = 36.5, 110.0, 111.4, 117.9, 119.6, 119.9, 122.4, 124.0, 127.2, 129.5, 131.4, 132.6, 134.8, 136.9, 140.2.
3,3¢-Bisindolyl(methyl)phenylmethane (3ae) IR: 741, 1010, 1336, 1455, 2848, 2923, 3053, 3410 cm–1.
EIMS: m/z (%) = 390 (100, M+), 392 [61, (M + 2)+], 274 (41), 245 (50), 176 (24), 117 (56).
1
Anal. Calcd for C23H16Cl2N2: C, 70.60; H, 4.12; N, 7.16. Found: C, 70.62; H, 4.20; N, 7.18. 3,3¢-Bisindolyl-4-fluorophenylmethane (3j) IR: 737, 862, 1039, 1502, 1600, 1502, 1456, 3059, 3440 cm–1. 1
H NMR (300 MHz, CDCl3): d = 5.87 (s, 1 H), 6.65 (s, 2 H), 6.96 (t, J = 8.4 Hz, 2 H), 7.02 (d, J = 7.8 Hz, 2 H), 7.20 (t, J = 7.8 Hz, 2 H), 7.27–7.32 (m, 2 H), 7.36 (d, J = 8.7 Hz, 4 H), 7.94 (br s, 2 H, NH). 13
C NMR (75 MHz, CDCl3): d = 39.6, 111.3, 115.0, 115.3, 119.5, 120.1, 122.2, 123.8, 127.1, 130.3, 136.9, 139.9, 160.0.
EIMS: m/z (%) = 340 (2, M+), 121 (100), 117 (38), 95 (12), 89 (42), 77 (9). Anal. Calcd for C23H17FN2: C, 81.16; H, 5.03; N, 8.23. Found: C, 81.22; H, 5.10; N, 8.16. 3,3¢-Bisindolyl-2-methylphenylmethane (3l) IR: 740, 1092, 1337, 1455, 1484, 1600, 2923, 3040, 3414 cm–1. 1
H NMR (300 MHz, CDCl3): d = 2.05 (s, 3 H), 5.87 (s, 1 H), 6.68 (s, 2 H), 7.02 (t, J = 8.1 Hz, 2 H), 7.16–7.21 (m, 6 H), 7.37 (d, J = 8.1 Hz, 4 H), 7.94 (br s, 2 H, NH).
13
1953
H NMR (300 MHz, CDCl3): d = 2.29 (s, 3 H), 6.54 (s, 2 H), 6.86 (t, J = 7.8 Hz, 2 H), 7.06 (t, J = 7.8, 2 H), 7.14–7.18 (m, 4 H), 7.23– 7.34 (m, 5 H), 7.78 (br s, 2 H, NH).
13
C NMR (75 MHz, CDCl3): d = 28.8, 43.7, 111.2, 118.9, 121.5, 122.1, 123.4, 124.7, 125.8, 126.5, 127.8, 128.1, 137.1, 148.1.
EIMS: m/z (%) = 336 (85, M+), 243 (100), 245 (48), 220 (58), 77 (38). Anal. Calcd for C24H20N2: C, 85.68; H, 5.99; N, 8.33. Found: C, 85.66; H, 5.98; N, 8.40. 3,3¢,3¢¢,3¢¢¢-Tetraindolyl(terephthalyl)dimethane (6) Colorless solid (contains 2 EtOAc molecules; EtOAc–hexane, 1:2); mp 138–139 °C (Lit.16b 138–140 °C). IR: 742, 776, 1295, 1455, 1720, 2849, 2920, 3052, 3411 cm–1. 1
H NMR (300 MHz, acetone-d6): d = 1.29 (t, J = 7.2 Hz, 6 H, CH3), 2.05 (s, 6 H, CH3), 4.04–4.09 (m, 4 H, CH2), 5.89 (s, 2 H, ArCH), 6.81 (t, J = 7.8 Hz, 4 H), 6.91 (t, J = 7.8 Hz, 4 H), 7.05 (t, J = 7.8 Hz, 4 H), 7.34–7.38 (m, 12 H), 9.97 (br s, 4 H, NH). 13
C NMR (75 MHz, acetone-d6): d = 14.4, 20.8, 40.8, 60.5, 112.0, 119.2, 120.0, 120.3, 121.9, 124.3, 124.5, 128.1, 129.2, 138.0, 143.4, 170.8. EIMS: m/z (%) = 566 (3, M+), 452 (10), 336 (68), 245 (10), 117 (8), 116 (100), 89 (50).
C NMR (75 MHz, CDCl3): d = 19.5, 36.2, 110.9, 119.2, 119.8, 121.9, 123.8, 125.8, 126.0, 127.2, 128.3, 130.1, 134.4, 136.0, 136.7, 142.0.
Anal. Calcd for C48H46N4O4: C, 77.60; H, 6.24; N, 7.54. Found: C, 77.62; H, 6.40; N, 7.48.
EIMS: m/z (%) = 336 (3, M+), 121 (100), 117 (57), 108 (34), 91 (17), 89(78), 77 (21).
2,2¢-Bis[(3,3¢-diindolyl)methylphenoxy]propane (7) Colorless solid (EtOAc–hexane); mp 145–147 °C.
Anal. Calcd for C24H20N2: C, 85.68; H, 5.99; N, 8.33. Found: C, 85.63; H, 6.03; N, 8.46.
IR: 742, 1240, 1467, 1596, 2849, 2924, 3055, 3415 cm–1.
3,3¢-Bisindolyl-2-methoxyphenylmethane (3n) IR: 745, 1102, 1337, 1456, 1486, 1595, 2932, 3056, 3407 cm–1. 1
H NMR (300 MHz, CDCl3): d = 3.82 (s, 3 H), 6.35 (s, 1 H), 6.64 (s, 2 H), 6.81 (t, J = 7.2 Hz, 1 H), 6.95 (t, J = 8.1 Hz, 1 H), 7.01 (d, J = 7.8 Hz, 2 H), 7.12–7.22 (m, 4 H), 7.33 (d, J = 8.1 Hz, 2 H), 7.40 (d, J = 7.8 Hz, 2 H), 7.84 (br s, 2 H, NH). 13
C NMR (75 MHz, CDCl3): d = 32.3, 56.0, 110.0, 110.8, 111.1, 119.2, 119.8, 120.2, 120.6, 121.9, 123.7, 127.3, 129.9, 132.5, 136.9, 157.1. +
+
EIMS: m/z (%) = 352 (35, M ), 351 [100, (M – 1) ], 335 (41), 245 (10), 236 (35), 220 (52). Anal. Calcd for C24H20N2O: C, 81.79; H, 5.72; N, 7.95. Found: C, 81.86; H, 5.78; N, 7.98. 3,3¢-Bisindolyl-4-allyloxyphenylmethane (3w) IR: 745, 791, 1455, 1506, 1608, 2849, 3052, 3418 cm–1.
1
H NMR (300 MHz, acetone-d6): d = 2.81–2.84 (m, 2 H), 3.86 (t, J = 8.7 Hz, 4 H), 6.34 (s, 2 H), 6.58 (d, J = 7.8 Hz, 2 H), 6.75–6.89 (m, 10 H), 7.02–7.12 (m, 8 H), 7.36 (t, J = 7.8 Hz, 8 H), 9.87 (br s, 4 H, NH). 13 C NMR (75 MHz, acetone-d6): d = 29.0, 33.1, 65.0, 112.1, 112.2, 119.2, 119.6, 120.1, 120.6, 121.9, 124.6, 127.8, 128.2, 129.8, 134.0, 138.0, 157.0.
EIMS: m/z (%) = 716 (3, M+), 482 (5), 480 (41), 117 (9), 116 (100), 89 (26). Anal. Calcd for C49H40N4O2: C, 82.10; H, 5.62; N, 7.82. Found: C, 82.12; H, 5.58; N, 7.80.
Acknowledgment The authors thank the National Natural Science Foundation of China (20472032) and the State Key Laboratory of Elemento-Organic Chemistry for financial support.
1
H NMR (300 MHz, CDCl3): d = 4.45 (dt, J = 5.2, 1.5 Hz, 2 H), 5.41 (dd, J = 14.2, 1.5 Hz, 2 H), 5.83 (s, 1 H), 6.01–6.12 (m, 1 H), 6.55 (s, 2 H), 6.83 (d, J = 8.4 Hz, 2 H), 7.02 (t, J = 7.2 Hz, 2 H), 7.18 (t, J = 6.0 Hz, 2 H), 7.37 (t, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 4 H), 7.91 (br s, 2 H, NH). 13
C NMR (75 MHz, CDCl3): d = 39.5, 69.0, 111.2, 114.6, 117.8, 119.4, 120.2, 122.1, 123.7, 127.2, 129.8, 133.7, 136.6, 136.9, 157.1. EIMS: m/z (%) = 378 (100, M+), 337 (29), 261 (42), 219 (63), 116 (83). Anal. Calcd for C26H22N2O: C, 82.51; H, 5.86; N, 7.40. Found: C, 82.56; H, 5.88; N, 7.36.
References (1) Sundberg, R. J. The Chemistry of Indoles; Academic Press: New York, 1970. (2) Ge, X.; Yannai, S.; Rennert, G.; Gruener, N.; Fares, F. A. Biochem. Biophys. Res. Commun. 1996, 228, 153. (3) Zeligs, M. A. J. Med. Food 1998, 1, 67. (4) Remers, W. Chem. Heterocycl. Compd. 1972, 25, 1. (5) (a) Kamal, A.; Qureshi, A. A. Tetrahedron 1963, 19, 513. (b) Noland, W. E.; Venkiteswaran, M. R.; Richards, G. G. J. Org. Chem. 1961, 26, 4241. (c) Noland, W. E.; Venkiteswaran, M. R. J. Org. Chem. 1961, 26, 4263. Synthesis 2005, No. 12, 1949–1954
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