Key words bisindolylmethanes - iron catalysts - alcohol oxidation - domino reactions - BINAM
ligand
1,1-Bisindolylmethanes and their derivatives are known to have a broad spectrum of
biological and pharmacological activities.[1 ] They are active against human breast cancer cells and are found to activate a specific
estrogen receptor.[2 ] These compounds show growth inhibitory activity toward lung cancer cells,[3 ] inhibit bladder cancer growth[4 ] and have antimicrobial,[5 ] antifungal,[6 ] antibacterial[7 ] and antitumor activities.[8 ] In addition, 1,1-bisindolylmethane derivatives are used as human dietary supplements.[9 ] The oxidized forms of 1,1-bisindolylmethanes have been reported as chromogenic-sensing
molecules.[10 ] As a result of their potential value in pharmaceuticals and materials, the synthesis
of this class of compounds has attracted significant interest from synthetic chemists.[11 ] 1,1-Bisindolylmethanes have been isolated from metabolites of terrestrial and marine
origin,[12 ] and various protocols have been adopted for their synthesis.[13 ] Most of the common methods involve the addition of indoles to aldehydes or ketones
in the presence of a Lewis acid,[14 ] a Bronsted acid,[15 ] transition metals,[16 ] rare earth catalysts[17 ] or zeolites.[18 ] However, many of these methods suffer from the disadvantages of using stoichiometric
amounts of acids, expensive metal catalysts and easily oxidizable aldehyde precursors.
There have been very few reports in the literature on the synthesis of 1,1-bisindolylmethanes
from alcohols.[19 ] Yokoyama et al. reported the synthesis of 1,1-bisindolylmethanes from benzyl alcohol
using a palladium catalyst.[20 ] Although, this method worked well, the protocol utilized costly palladium as the
catalyst and was limited to benzylic alcohols as substrates. Hence, there is a need
for an efficient, economic and ecofriendly catalyst for the synthesis of 1,1-bisindolylmethanes
starting from primary alcohols.
Iron is an attractive alternative catalyst because of its abundance, low price and
environmentally benign character.[21 ] Unlike other metals, iron is involved as a key element in various biological systems,
particularly in oxidations. Due to its ability to undergo facile changes in oxidation
state and because of its distinct Lewis acid character, iron catalysts enable a broad
range of synthetic transformations such as oxidation, cross-coupling, alkylation and
addition reactions.[22 ] In continuation of our research on environmentally friendly iron-catalyzed reactions,[23 ] herein, we report an efficient iron(II) chloride–(±)-1,1′-binaphthyl-2,2′-diamine
[FeCl2 –(±)-BINAM] complex catalyzed synthesis of 1,1-bisindolylmethanes from primary alcohols
and indoles in a domino fashion.[24 ]
In our preliminary studies, the synthesis was carried out starting from ethanol via
a domino alcohol oxidation in the presence of the FeCl2 –BINAM complex as the catalyst and dicumyl peroxide (DCP), followed by condensation
of the resulting aldehyde with indole (1 ) in ethanol, at 120 °C. To our surprise, the bisindolyl product was formed in 68%
isolated yield after eight hours (Scheme [1 ]). It is noteworthy that the reaction did not proceed without the iron catalyst.
Scheme 1 Synthesis of bisindolylmethane 2 from indole
Figure 1 Ligand screening for the domino synthesis of 2
In order to improve the reaction efficiency, several BINAM-derived and other ligands
were screened, but none of them provided a better yield compared to BINAM (L1 ) (Figure [1 ]). When the reaction was carried out with iron(II) chloride, but without a ligand,
only a 27% yield of the product was obtained.
To optimize the conditions in terms of the yield, we screened several other metal
salts in combination with BINAM (L1 ) as the ligand in this domino reaction (Table 1). Although copper, cobalt and zinc
salts catalyzed the reaction, none of them provided better yields than iron(II) chloride.
It was found that when a higher oxidation state iron catalyst (Fe3+ ) was used, no product formation was observed. The best result was obtained with iron(II)
chloride (5 mol%), which gave bisindolylmethane 2 in 75% yield after six hours. The results are summarized in Table 1.
Table 1 Screening of Metal Salts for the Synthesis of 2
Entry
Metal salt
Time (h)
Yield (%)a
1
FeCl2
6
68
2
Fe(OAc)2
16
40
3
FeSO4
16
15
4
FeCl3
24
0
5
FeBr3
20
0
6
Fe(ClO4 )2
15
0
7
CuCl2
12
14
8
Cu(OAc)2
12
42
9
Cu(OTf)2
12
45
10
CuI
24
25
11
Co(OAc)2
12
20
12
Ni(OAc)2
24
20
13
Zn(OAc)2
16
38
14
FeCl2
8
50b
15
FeCl2
6
75
c
16
FeCl2
8
69d
17
FeCl2
12
70e
a Yield of isolated product.
b FeCl2 (2.5 mol%).
c FeCl2 (5 mol%) and L1 (10 mol%).
d FeCl2 (10 mol%) and L1 (10 mol%).
e FeCl2 (10 mol%) and L1 (20 mol%).
Next, different types of oxidizing agents were examined. Oxidants including hydrogen
peroxide (H2 O2 ), tert -butyl hydroperoxide (t -BuOOH) and benzoyl peroxide were less effective for the formation of product 2 when compared with dicumyl peroxide (DCP). The reaction was also attempted with 2,2,6,6-tetramethylpiperidine
1-oxyl (TEMPO) and molecular oxygen as the oxidant, however, there was no product
formation. The number of equivalents of dicumyl peroxide used was important with 3.5
equivalents giving the best result.
Since the temperature plays a major role in catalyst efficiency, the reaction was
examined at different temperatures. When the temperature was lowered to 80 °C, the
yield of product 2 (76%) remained almost the same (Table 2, entry 9). However, when the temperature
was reduced to 60 °C, the yield decreased to 62% (Table 2, entry 10).
Table 2 Screening of Oxidants for the Synthesis of 2
Entry
Oxidant
Temp (°C)
Time (h)
Yield (%)a
1
DCP
120
6
75
2
H2 O2
120
16
0
3
t -BuOOH
120
16
0
4
(PhCO2 )2
120
18
trace
5
TEMPO
120
40
0b
6
DCP
120
48
0c
7
DCP
120
18
55d
8
DCP
100
10
72
9
DCP
80
6
76
10
DCP
60
12
62
11
DCP
r.t.
24
0
a Yield of isolated product.
b O2 was used as a co-oxidant.
c TEMPO (1.0 equiv) was added.
d DCP (2.0 equiv).
From the optimization studies the best catalytic system was found to be: iron(II)
chloride (5 mol%), 1,1′-binaphthyl-2,2′-diamine (L1 ) (10 mol%), dicumyl peroxide (3.5 equiv), 80 °C. The substrate scope of this methodology
was evaluated using the optimized reaction conditions and the results are summarized
in Table 3. Notably, indole reacted with ethanol to give the important natural product,
vibrindole A (2 ) (Table 3, entry 1). For substituted indoles, it was found that the presence of an
electron-releasing group on the nitrogen atom resulted in a good yield of the corresponding
product (Table 3, entry 2). However, electron-withdrawing groups on the indole nitrogen
atom, such as tosyl, completely inhibited the reaction (Table 3, entry 8), whilst
an electron-withdrawing group on the benzene ring reduced the yield (Table 3, entry
5).
Increasing the length of the aliphatic chain of the alcohol led to reduced yields;
when the alkyl chain was more than three carbon atoms long, the reaction did not take
place. In the case of benzyl alcohol the reaction required a longer time than aliphatic
alcohols (Table 3, entries 11–14).
Table 3 Iron-Catalyzed Domino Synthesis of Bisindolylmethanes from Indoles and Alcohols
Entry
Indole
Alcohol
Product
Time (h)
Yield (%)
1
2
6
76a
2
3
6
80
3
4
24
62
4
5
12
70
5
6
36
63
6
7
15
63
7
8
48
54
8
9
24
0
9
10
10
85
10
11
36
62
11
12
36
60b,c
12
13
48
62b,c
13
14
48
58b,c
14
15
36
59b,c
a Yield of isolated product.
b tert -Butyl hydroperoxide was used as the oxidant.
c tert -Butyl alcohol (2 mL) was used as the solvent.
The reaction was completely suppressed by adding one equivalent of TEMPO (with respect
to FeCl2 ), a radical trapping agent, to the reaction mixture. These results indicate that
a radical intermediate is most likely involved in the initial steps of the domino
transformation. This explains the observed fact that aliphatic alcohols are more reactive
than benzyl alcohol, since benzylic radicals are stabilized by resonance effects.
When a secondary alcohol was subjected to the optimized conditions there was no reaction
at all. These observations prove that the first step involves oxidation of the alcohol
into an aldehyde. More importantly, there was no product formation at all when the
strongly electron-deficient indole, N -tosylindole was used. The second step might involve nucleophilic attack of indole,
which is directed by the lone pair of electrons on the nitrogen of the indole.
Scheme 2 A plausible mechanism for the domino synthesis of bisindolylmethanes
Based on these observations, a plausible mechanism for the domino synthesis of bisindolylmethanes,
using 2 as an example, is suggested (Scheme [2 ]). Two catalytic cycles are proposed in the mechanism. In the first cycle, the primary
alcohol 16 is oxidized by iron(II) chloride and dicumyl peroxide to give the corresponding aldehyde
19 through the radical intermediates 17 and 18 . In the second cycle, nucleophilic addition of indole (1 ) to the iron(II) chloride activated aldehyde 19 (which is formed in first the cycle) affords secondary alcohol 20a (see Scheme [3 ]). The secondary alcohol is further activated by iron(II) chloride and undergoes
a second addition of indole to give the bisindolylmethane 2 . We anticipated that the reaction proceeded through the secondary alcohol 20a of the intermediate 20 , and we thus carried out a control experiment to understand the mechanism. The intermediate
20a was synthesized by the reduction of 3-acetylindole using sodium borohydride,[25 ] and then subjected to our standard conditions for the preparation of bisindolylmethanes.
As expected, the reaction took place smoothly and afforded an 80% isolated yield of
compound 2 (Scheme [3 ]). The instability of the intermediate 20a explains the adverse effect of high temperature on this reaction.[26 ]
Scheme 3 Synthesis of bisindolylmethane 2 from indole and the secondary alcohol 20a
In summary, an efficient, cost-effective, and environmentally friendly iron-catalyzed
domino synthesis of bisindolylmethanes and their derivatives from indoles and primary
alcohols has been reported. A plausible mechanism has been proposed for this domino
process. In support of the mechanism, one of the postulated reaction intermediates
was independently synthesized and converted into the corresponding bisindolylmethane
under the same reaction conditions.
All reactions were carried out in screw-cap pressure tubes under N2 . All the solvents used for the reactions were obtained from Merck, India and were
dried according to standard procedures. EtOH was purchased from Changshu Yangyuan
Chemical, China, and dried over 4 Å molecular sieves. Reactions were monitored by
thin-layer chromatography (TLC) using Merck silica gel 60 F254 precoated plates (0.25
mm), and samples were made visual by UV fluorescence. Silica gel (particle size: 100–200
mesh) was purchased from SRL India and was used for column chromatography using appropriate
mixtures of hexanes–EtOAc as the eluent. FeCl2 was obtained from Sigma-Aldrich Company. Other chemicals were purchased: indole from
Spectrochem Pvt. Ltd., Mumbai, India (AR), dicumyl peroxide from Acros Organics, and
1,1′-binaphthyl-2,2′-diamine (BINAM) ligand L1 was purchased from GERCHEM chemicals, Hyderabad, India. Reaction temperatures were
controlled using a Varivolt temperature modulator. Melting points were obtained using
a Toshniwal melting point apparatus and are uncorrected. FTIR spectra were recorded
on a Nicolet 6700 spectrometer and absorptions are reported in wavenumbers (cm–1 ). 1 H and 13 C NMR spectra were recorded on Bruker 400 or 500 MHz instruments. 1 H NMR spectra are reported relative to Me4 Si (δ 0.0) or residual CHCl3 (δ 7.26). 13 C NMR are reported relative to CDCl3 (δ 77.16). High-resolution mass spectra (HRMS) were recorded on Q-Tof Micro mass
spectrometer.
3,3′-(Ethane-1,1-diyl)bis(1H -indole) (2);[27 ] Typical Procedure
3,3′-(Ethane-1,1-diyl)bis(1H -indole) (2);[27 ] Typical Procedure
An oven-dried, screw-cap pressure tube containing a magnetic stir bar was charged
with FeCl2 (3.2 mg, 0.025 mmol), 1,1′-binaphthyl-2,2′-diamine (BINAM) (14.2 mg, 0.05 mmol),
dicumyl peroxide (DCP) (473.2 mg, 1.75 mmol) and indole (1 ) (58.6 mg, 0.5 mmol). The pressure tube was evacuated and back-filled with N2 . Anhydrous EtOH (2 mL) was added and the mixture was stirred at 80 °C for 6 h. After
the complete disappearance of indole (the progress of the reaction was monitored by
TLC), the mixture was allowed to cool to r.t. and the EtOH was evaporated under reduced
pressure using a rotary evaporator. Next, H2 O (15 mL) was added, and the product was extracted with EtOAc (3 × 10 mL) and dried
over anhydrous Na2 SO4 . The solvent was evaporated and the residue purified by column chromatography on
silica gel (EtOAc–hexane, 12:88) to afford pure product 2 .
Yield: 49.8 mg (76%); light yellow solid; mp 148 °C (Lit.[27 ] 158–160 °C); Rf
= 0.39 (20% EtOAc in hexane).
IR (neat): 3413, 3053, 2969, 2871, 1456, 1417, 1340, 1221, 1092, 1012, 746, 585 cm–1 .
1 H NMR (400 MHz, CDCl3 ): δ = 1.83 (d, J = 7.2 Hz, 3 H), 4.70 (q, J = 7.2 Hz, 1 H), 6.89 (d, J = 2.4 Hz, 2 H), 7.08 (td, J = 8, 0.8 Hz, 2 H), 7.20 (td, J = 8.0, 0.8 Hz, 2 H), 7.34 (d, J = 8 Hz, 2 H), 7.61 (d, J = 8.4 Hz, 2 H), 7.80 (br s, 2 H).
13 C NMR (100 MHz, CDCl3 ): δ = 21.9, 28.3, 111.2, 119.1, 119.9, 121.3, 121.8, 121.9, 127.0, 136.8.
HRMS (ESI, +): m /z [M + Na]+ calcd for C18 H16 N2 Na: 283.1211; found: 283.1220.
3,3′-(Ethane-1,1-diyl)bis(1-methyl-1H -indole) (3)
3,3′-(Ethane-1,1-diyl)bis(1-methyl-1H -indole) (3)
Yield: 58.4 mg (80%); colorless oil; Rf
= 0.77 (20% EtOAc in hexane).
IR (neat): 2925, 1612, 1469, 739 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 1.71 (d, J = 7.0 Hz, 3 H), 3.63 (s, 6 H), 4.59 (q, J = 7.1 Hz, 1 H), 6.71 (s, 2 H), 6.96 (t, J = 7.0 Hz, 2 H), 7.12 (td, J = 7.0, 1.1 Hz, 2 H), 7.20 (t, J = 8.2 Hz, 2 H), 7.51 (d, J = 8 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 22.5, 28.3, 32.9, 109.4, 118.7, 120.1, 120.6, 121.6, 126.3, 127.6, 137.6.
HRMS (ESI, +): m /z [M + H]+ calcd for C20 H21 N2 : 289.1705; found: 289.1714.
3,3′-(Ethane-1,1-diyl)bis(1-ethyl-1H -indole) (4)
3,3′-(Ethane-1,1-diyl)bis(1-ethyl-1H -indole) (4)
Yield: 49.7 mg (62%); pale brown solid; mp 101 °C; Rf
= 0.54 (5% EtOAc in hexane).
IR (KBr): 2929, 2869, 1607, 1547, 1462, 1394, 1334, 931, 819 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 1.33 (t, J = 7 Hz, 6 H), 1.72 (d, J = 7 Hz, 3 H), 4.02 (dq, J = 7.0, 1.5 Hz, 4 H), 4.59 (q, J = 7.5 Hz, 1 H), 6.77 (s, 2 H), 6.95 (t, J = 7 Hz, 2 H), 7.10 (t, J = 7.5 Hz, 2 H), 7.23 (d, J = 8.5 Hz, 2 H), 7.50 (d, J = 8 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 15.5, 22.2, 28.2, 40.8, 109.2, 118.3, 120.0, 121.1, 124.3, 125.6, 127.9, 136.3.
HRMS (ESI, +): m /z [M + K]+ calcd for C22 H24 N2 K: 355.1577; found: 355.1589.
3,3′-(Propane-1,1-diyl)bis(5-methoxy-1H -indole) (5)
3,3′-(Propane-1,1-diyl)bis(5-methoxy-1H -indole) (5)
Yield: 58.2 mg (70%); brown solid; mp 121 °C; Rf
= 0.41 (30% EtOAc in hexane).
IR (KBr): 3409, 2924, 2853, 1617, 1452, 1309, 1089, 878, 800, 760 cm–1 .
1 H NMR (400 MHz, CDCl3 ): δ = 1.02 (t, J = 7.2 Hz, 3 H), 2.23 (quin, J = 7.2 Hz, 2 H), 3.77 (s, 6 H), 4.27 (t, J = 7.2 Hz, 1 H), 6.81 (dd, J = 8, 2 Hz, 2 H), 6.99 (d, J = 1.6 Hz, 2 H), 7.03 (d, J = 2 Hz, 2 H), 7.22 (d, J = 8 Hz, 2 H), 7.81 (br s, 2 H).
13 C NMR (100 MHz, CDCl3 ): δ = 13.3, 28.2, 55.7, 56.0, 102.1, 111.7, 118.8, 122.4, 128.3, 128.4, 144.6, 158.0.
3,3′-(Ethane-1,1-diyl)bis(5-bromo-1-methyl-1H -indole) (6)[28 ]
3,3′-(Ethane-1,1-diyl)bis(5-bromo-1-methyl-1H -indole) (6)[28 ]
Yield: 65.8 mg (63%); brown solid; mp 112 °C; Rf
= 0.41 (10% EtOAc in hexane).
IR (neat): 3114, 2968, 2821, 1611, 1535, 1420, 1366, 907, 866, 790 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 1.66 (d, J = 7.0 Hz, 3 H), 3.62 (s, 6 H), 4.44 (q, J = 7.0 Hz, 1 H), 6.69 (s, 2 H), 7.07 (d, J = 8.5 Hz, 2 H), 7.19 (dd, J = 8.5, 2.0 Hz, 2 H), 7.57 (d, J = 2 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 22.1, 28.0, 32.9, 110.8, 112.2, 119.6, 122.3, 124.4, 127.3, 128.9, 136.2.
3,3′-(Ethane-1,1-diyl)bis(5-methoxy-1H -indole) (7)[28 ]
3,3′-(Ethane-1,1-diyl)bis(5-methoxy-1H -indole) (7)[28 ]
Yield: 50.6 mg (63%); brown sticky solid; Rf
= 0.43 (30% EtOAc in hexane).
IR (KBr): 3412, 2954, 2830, 1619, 1479, 1361, 1212, 805, 739 cm–1 .
1 H NMR (400 MHz, CDCl3 ): δ = 1.79 (d, J = 7.2 Hz, 3 H), 3.77 (s, 6 H), 4.57 (q, J = 6.8 Hz, 1 H), 6.83 (d, J = 9.2 Hz, 2 H), 6.92 (s, 2 H), 7.01 (s, 2 H), 7.23 (s, 2 H), 7.81 (s, 2 H).
13 C NMR (100 MHz, CDCl3 ): δ = 21.6, 28.2, 56.0, 101.9, 111.7, 111.8, 121.3, 122.2, 127.4, 132.0, 153.6.
3,3′-(Ethane-1,1-diyl)bis[1-(4-methoxyphenyl)-1H -indole] (8)
3,3′-(Ethane-1,1-diyl)bis[1-(4-methoxyphenyl)-1H -indole] (8)
Yield: 63.7 mg (54%); brown solid; mp 89 °C; Rf
= 0.46 (10% EtOAc in hexane).
IR (KBr): 3049, 2925, 2838, 1607, 1457, 1370, 1246, 834, 743 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 1.80 (d, J = 7.5 Hz, 3 H), 3.77 (s, 6 H), 4.69 (q, J = 7 Hz, 1 H), 6.91 (d, J = 8.5 Hz, 4 H), 7.02 (m, 4 H), 7.11 (t, J = 7 Hz, 2 H), 7.29 (d, J = 9 Hz, 4 H), 7.37 (d, J = 8.5 Hz, 2 H), 7.59 (d, J = 8 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 22.0, 28.2, 55.7, 110.5, 114.7, 119.5, 120.0, 121.9, 122.2, 125.6, 125.9, 128.1,
133.2, 136.9, 158.0.
HRMS (ESI, +): m /z [M + Na]+ calcd for C32 H28 N2 O2 Na: 495.2048; found: 495.2068.
3,3′-(Propane-1,1-diyl)bis(1H -indole) (10)[29 ]
3,3′-(Propane-1,1-diyl)bis(1H -indole) (10)[29 ]
Yield: 58.2 mg (85%); colorless oil; Rf
= 0.45 (20% EtOAc in hexane).
1 H NMR (500 MHz, CDCl3 ): δ = 0.93 (t, J = 7.4 Hz, 3 H), 2.16 (quin, J = 7.4 Hz, 2 H), 4.29 (t, J = 7.4 Hz, 1 H), 6.87 (d, J = 2.2 Hz, 2 H), 6.95 (t, J = 7.1 Hz, 2 H), 7.06 (t, J = 7.6 Hz, 2 H), 7.22 (d, J = 8.1 Hz, 2 H), 7.51 (d, J = 8 Hz, 2 H), 7.75 (s, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 13.2, 28.8, 36.0, 111.1, 119.1, 119.8, 120.4, 121.5, 121.8, 127.3, 136.7.
3,3′-(Propane-1,1-diyl)bis(1-methyl-1H -indole) (11)
3,3′-(Propane-1,1-diyl)bis(1-methyl-1H -indole) (11)
Yield: 46.5 mg (62%); dark red solid; Rf
= 0.56 (10% EtOAc in hexane).
IR (KBr): 2923, 1607, 1465, 1370, 1086, 747 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 0.93 (t, J = 7.5 Hz, 3 H), 2.14 (q, J = 7.5 Hz, 2 H), 3.64 (s, 6 H), 4.29 (t, J = 7.0 Hz, 1 H), 6.77 (s, 2 H), 6.94–6.97 (m, 2 H), 7.09–7.12 (m, 2 H), 7.18 (s, 2
H), 7.53 (d, J = 8 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 13.3, 29.4, 32.8, 35.9, 109.2, 118.5, 119.1, 119.9, 121.3, 126.4, 127.7, 137.4.
HRMS (ESI, +): m /z [M + Na]+ calcd for C21 H22 N2 Na: 325.1681; found: 325.1696.
3,3′-(Phenylmethane-1,1-diyl)bis(1H -indole) (12)[30 ]
3,3′-(Phenylmethane-1,1-diyl)bis(1H -indole) (12)[30 ]
Yield: 48.3 mg (60%); pink solid; mp 139 °C (Lit.[30 ] 141–142 °C); Rf
= 0.49 (20% EtOAc in hexane).
IR (KBr): 3409, 2924, 2853, 1605, 1455, 1198, 744 cm–1 .
1 H NMR (400 MHz, CDCl3 ): δ = 5.80 (s, 1 H), 6.55 (d, J = 1.6 Hz, 2 H), 6.92 (t, J = 7.2 Hz, 2 H), 7.06–7.14 (m, 3 H), 7.19 (t, J = 7.2 Hz, 2 H), 7.25–7.27 (m, 4 H), 7.31 (d, J = 8 Hz, 2 H), 7.79 (s, 2 H).
13 C NMR (100 MHz, CDCl3 ): δ = 40.2, 111.0, 119.2, 119.9, 121.9, 123.6, 126.1, 127.1, 128.2, 128.7, 133.7,
136.7, 144.0.
3,3′-(Phenylmethane-1,1-diyl)bis(1-methyl-1H -indole) (13)[27 ]
3,3′-(Phenylmethane-1,1-diyl)bis(1-methyl-1H -indole) (13)[27 ]
Yield: 54.2 mg (59%); dark red solid; mp 163 °C; Rf
= 0.43 (10% EtOAc in hexane).
IR (KBr): 3020, 2927, 1607, 1547, 1472, 1366, 744, 700 cm–1 .
1 H NMR (400 MHz, CDCl3 ): δ = 3.66 (s, 6 H), 5.87 (s, 1 H), 6.52 (d, J = 0.8 Hz, 2 H), 6.96–7.00 (m, 2 H), 7.16–7.21 (m, 3 H), 7.24–7.29 (m, 4 H), 7.33–7.35
(m, 2 H), 7.38 (d, J = 7.6 Hz, 2 H).
13 C NMR (100 MHz, CDCl3 ): δ = 32.8, 40.2, 109.2, 118.4, 118.8, 120.2, 121.5, 126.1, 127.6, 128.3, 128.4,
128.8, 137.5, 144.6.
HRMS (ESI, +): m /z [M + Na]+ calcd for C25 H22 N2 Na: 373.1681; found: 373.1696.
3,3′-(Phenylmethane-1,1-diyl)bis(5-methoxy-1H -indole) (14)[28 ]
3,3′-(Phenylmethane-1,1-diyl)bis(5-methoxy-1H -indole) (14)[28 ]
Yield: 55.4 mg (58%); red solid; mp 198 °C; Rf
= 0.56 (30% EtOAc in hexane).
IR (KBr): 3004, 2934, 1619, 1586, 1484, 1448, 1208, 1028, 799 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 3.61 (s, 6 H), 5.69 (s, 1 H), 7.11–7.22 (m, 7 H), 7.27 (d, J = 7.2 Hz, 2 H), 7.39 (t, J = 7.6 Hz, 2 H), 7.76 (s, 2 H), 8.04 (d, J = 7.6 Hz, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 40.4, 56.0, 102.2, 111.8, 112.0, 119.5, 124.6, 126.2, 128.3, 128.6, 128.9,
130.3, 132.0, 133.8.
HRMS (ESI, +): m /z [M + Na]+ calcd for C25 H22 N2 O2 Na: 405.1579; found: 405.1566.
3,3′-(Phenylmethane-1,1-diyl)bis(5-bromo-1H -indole) (15)[31 ]
3,3′-(Phenylmethane-1,1-diyl)bis(5-bromo-1H -indole) (15)[31 ]
Yield: 59.1 mg (59%); dark red solid; mp 223 °C; Rf
= 0.55 (30% EtOAc in hexane).
IR (KBr): 3416, 3068, 2927, 2859, 1592, 1558, 1449, 976, 775 cm–1 .
1 H NMR (500 MHz, CDCl3 ): δ = 5.75 (s, 1 H), 6.65 (d, J = 1.5 Hz, 2 H), 7.23–7.24 (m, 4 H), 7.26 (s, 2 H), 7.29–7.30 (m, 4 H), 7.47 (d, J = 0.5 Hz, 2 H), 7.99 (s, 2 H).
13 C NMR (125 MHz, CDCl3 ): δ = 40.0, 112.7, 112.8, 119.2, 122.4, 124.9, 125.1, 126.7, 128.6, 128.7, 128.8,
135.5, 143.1.
HRMS (ESI, +): m /z [M + H]+ calcd for C23 H17 N2 Br2 : 478.9758; found: 478.9743.
