Introducing tetramethylurea as a new methylene precursor: a microwave-assisted RuCl3-catalyzed cross dehydrogenative coupling approach to bis(indolyl)methanes

Article abstract of DOI:10.1039/c6ob02671k

Herein we report a microwave assisted Ru(iii)/TBHP-mediated reaction of indoles with tetramethylurea (TMU) synthesizing symmetrical as well as unsymmetrical bis(indolyl)methanes, where TMU acts as a methylenating agent. This is the first report where TMU is used as a methylene source. Moreover, the synthesis of unsymmetrical bis(indolyl)methanes by using a carbon precursor is also reported herein for the first time. Various substituted indoles are used for the reaction. The reaction is high yielding and takes a much shorter time to accomplish compared to the existing methods.

Full text of DOI:10.1039/c6ob02671k

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Introducing tetramethylurea as a new methylene precursor:
Microwave-assisted RuCl3-catalyzed cross dehydrogenative
coupling approach to bis(indolyl)methanes
Received 00th January 20xx,
Accepted 00th January 20xx
Mohit L. Deb,a* Paran J. Borpatra,a Prakash J. Saikiab and Pranjal K. Baruaha*
DOI: 10.1039/x0xx00000x
Here we report a microwave assisted Ru(III)/TBHP-mediated reaction of indoles with tetramethylurea (TMU) synthesizing
symmetrical as well as unsymmetrical bis(indolyl)methanes, where TMU acts as a methylenating agent. This is the first
report where TMU is used as methylene source. Moreover, The synthesis of unsymmetrical bis(indolyl)methanes by using
carbon precursor is also reported here for the first time. Various substituted indoles are used for the reaction. The reaction
is high yielding and takes much shorter time to accomplish compared to existing methods.
www.rsc.org/
reports are available for the synthesis of substituted BIMs,
however, BIMs having methylene bridge is difficult to
synthesize by usual coupling of indoles with formaldehyde.7
Introduction
Functionalization of amines via C-H activation has recently
attracted much attention in organic chemistry and the fine
chemical industry as functionalized amines are highly useful
intermediates for the synthesis of many pharmaceuticals and
They are synthesized by the acid catalyzed dimerization of
indole-3-carbinol, which itself is very difficult to prepare
because of its high instability.8 Jaisankar9a and Li et al.9b
synthesized them by using hexamethylenetetramine and
tetramethylethylenediamine as methylene precursors. These
methods either require high catalyst loading9b or longer
reaction time.9a
functional
materials.1
Direct
introduction
of
a
substituent/functional group at the
α
-position of tertiary
amines has usually been achieved by using transition metal
catalysts with an oxidant to generate the iminium ion, which
subsequently reacts with various C/N/O/S nucleophiles.2 When
such reactions are carried out under microwave irradiation, it
becomes more interesting as the technique offers simple,
clean, fast, efficient, and economic way for the synthesis of
many organic molecules compared to conventional thermal
methods. Therefore, this generates the momentum for many
chemists to switch from conventional heating to microwave
assisted technique.3
Previous Work
O
H
N
CuCl, TBHP
140 oC, 14h
30-93%
N
R
N
N
R
R
O
N
Bis(heterocycle)methanes have attracted much attention of
organic chemists in recent years due to their broad spectrum
of biological activities. For example, bis(indolyl)methanes
(BIM) and its derivatives are available as dietary supplements,
which increases the 2-hydroxylation of estrogen metabolites,
that helps to reduce the risk of breast and prostate cancer.4 It
is also used to treat recurrent respiratory papillomatosis, a
rare respiratory disease with tumors in the upper respiratory
tracts.5 In addition, due to its innate immune modulating
properties, BIM is also under investigation as a treatment for a
variety of viral and bacterial infections.6 Although numerous
Ar
VO(acac)2, IBD
150 oC, 6h
50-71%
N
N
N
R/H
Ar
R/H
Ar
R/H
O
This Work
N
N
RuCl3.3H2O / TBHP
MW, 110 o
N
R
1
N
N
C
R
10-18 mins.
71-93%
R
2
Scheme1. Reaction of indoles with different carbon precursors
aDepartment of Applied Sciences, GUIST, Gauhati University, Guwahati-781014, Results and discussion
Assam, India; Tel/Fax: +91-8876998905; E-mails: mohitdd.deb@gmail.com,
N,N-Dimethylformamide (DMF)10 and dimethylsulfoxide
baruah.pranjal@gmail.com.
b Analytical chemistry division, CSIR-NEIST, Jorhat-785006.
Electronic Supplementary Information (ESI) is available: See
DOI: 10.1039/x0xx00000x
(DMSO)11 are well known polar aprotic solvents, have already
proven to be
a
multipurpose reagents used for the
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Table 1. Optimization of the reaction[a]
Entry
Catalyst
(mol %)
Oxidant (eq.)
Solvent
Temp. (oC)
Time (mins.)
Yield (%)[c]
MW (Thermal)
MW (Thermal)
MW (Thermal)
1
2
Cu(OAc)2.H2O (10)
CuBr (10)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)[b]
TBHP (1)
TBHP (3)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
TBHP (2)
H2O2 (2)
DTBP (2)
K2S2O8 (2)
air
---
---
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
110 (reflux)
110 (reflux)
110 (reflux)
110 (reflux)
110 (130)
110 (130)
110 (130)
110 (130)
110 (130)
15 (120)
20 (180)
20 (180)
20 (180)
10 (90)
60 (56)
40 (32)
none
3
FeCl3.6H2O (10)
AgNO3 (10)
---
4
---
none
5
RuCl3.3H2O (10)
I2 (10)
---
85 (77)
48 (42)
50 (46)
72 (65)
68 (60)
82 (71)
85 (76)
72 (64)
61 (52)
42 (40)
38 (25)
49 (36)
66 (63)
trace (n.r.)[d]
trace (n.r.)
n.r. (n.r.)
n.r. (n.r.)
6
---
20 (180)
20 (180)
10 (90)
7
TBAI (10)
---
8
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (5)
RuCl3.3H2O (3)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (10)
RuCl3.3H2O (100)
---
9
---
10 (90)
10
11
12
13
14
15
16
17
18
19
20
21[e]
---
10 (90)
---
10 (90)
---
10 (90)
Toluene
CH3CN
EtOH
H2O
---
15 (120)
20 (180)
15 (180)
15 (120)
15 (90)
---
20 (180)
20 (180)
20 (180)
20 (180)
---
---
---
---
[a] Unless otherwise mentioned, all the reactions were performed by using 1a (1.0 mmol, 131 mg) and TMU (2.0 mmol, 232 mg). TBHP (5.5M in decane) was used. [b]
TBHP (70 % in water) was used. [c] Products were purified by column chromatography by using silica gel (100-200 mesh) and yields are for the isolated products. [d]
n.r.: no reaction. [e] The reaction was performed on 0.5 mmol scale.
introduction of diverse units including -CH2 and -CH3. N,N- Different catalysts and oxidants were screened for the
Dimethylacetamide (DMA) is another aprotic solvent used for reaction. We compared the yield of the reaction in both the
the similar purpose.12 Recently, DMF and DMA were used as a microwave and thermal condition, but obtained better yield in
methylene source for the synthesis of 3,3-bis(indolyl)methane shorter time by using the former technique (Table 1). We then
(BIM) in presence of transition metal catalysts (Scheme 1).13 established that RuCl3.3H2O (5 mol %) and tert-butyl
Although the methods give moderate yield, but require long hydroperoxide (TBHP in decane, 2 eq) in TMU (2 eq) at 110 ˚C
reaction time, high temperature or only 2-aryl substituted under microwave irradiation were the optimized conditions for
indole as substrate and, therefore, developing a method with the reaction (entry 11, Table 1). Screening of other oxidants
shorter reaction time and better substrate compatibility is in such as H2O2 gave us 61 % yield, whereas DTBP and K2S2O8
demand. Tetramethylurea (TMU) is also an aprotic solvent produced only traces of product (entries 17-19, Table 1).
used in organic synthesis. It is widely obtained as a byproduct However, no reaction took place when air was used as the
in pharmaceutical industry from the amide coupling reaction oxidant (entry 20, Table 1). We then checked the reaction with
when benzotriazolyluronium salts (e.g. HBTU, HATU) are used different amount of TBHP and found that both the decrease
as coupling agents.14 In continuation of our work on the α-C-H and increase of the loading of TBHP result in decrease in the
functionalization of tertiary amine,15 here we disclose TMU as yield (entry 9 and 10, Table 1). On the other hand, decreasing
a new methylene precursor for the synthesis of BIMs catalyzed the amount of RuCl3.3H2O from 5 to 3 mol % decreases the
by RuCl3.3H2O under microwave irradiation (Scheme 1). To the yield (entry 12, Table 1). However, no effect was observed on
best of our knowledge, this is the first report of the application the yield with increased catalyst loading (entry 5, Table 1). Use
of TMU as a methylene precursor.
of other catalysts such as Cu(II), Cu(I), Fe(III), Ag(I) and
molecular I2 provided lower yield. A variety of solvents was
also checked, but none of them produced good yield.
We considered the conversion of 1a into 2a as the model
reaction for the optimization of the reaction condition.
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"methylene source"
(Table 1). When DMF, DMA and DMSO were used as
methylene precursors, they produced lower yield of the
product compared to TMU under optimized condition (Scheme
2).
1a
2a
RuCl3.3H2O (5 mol %)
TBHP (2 eq)
MW, 110 o
C
10 mins.
TMU, DMA, DMF, DMSO
(85%) (61%) (58%) (26%)
Having identified the optimized conditions, we next
investigated the substrate scope for the synthesis of BIMs
(Scheme 3). We used a variety of N-substituted indoles and to
our delight, the resultant BIMs were obtained in good to
excellent yield. N-alkylindole produced higher yield than N-
benzyl/allylindole. The yield of the product was not affected
when electron-donating group is present on the phenyl ring of
indole (e.g., 2h Scheme 3). On the other hand, presence of
electron-withdrawing group produced comparatively lower
yield (e.g., 2c Vs 2i, Scheme 3). When 7-aza-1-methylindole
was used, we did not obtain any product (2u, Scheme 3). The
reason we believe is that the nitrogen atom on the phenyl ring
of indole may coordinate to the metal catalyst which prevents
the reaction. N-H indoles did not react in this condition.
However, when 1:1 mixture of N-methylindole (1a) and N-H
indole (1'a) was used under the optimized condition, we
obtained unsymmetrical BIM (2'a) as the major product along
with symmetrical BIM (2a) as minor (Scheme 4). As the
synthesis of unsymmetrical BIMs was difficult by other
Scheme 2. Comparison of yield of BIM with different methylene precursors
N
N
N
N
N
N
Me
Me
Me
Me
Me
Et
Me
Et
2c, 93%, 10 mins.
2b, 88%, 10 mins.
2a, 85%, 10 mins.
Br
Br
N
N
N
N
N
N
Me
Me
Et
Et
Pr
Pr
Et
Et
2e, 87%, 10 mins.
2d, 91%, 10 mins.
2f, 85%, 10 mins.
Br
MeO
NC
Br
OMe
CN
N
N
N
Pr
N
N
N
Pr
Me
Et
Et
2i, 75%, 12 mins.
Me
2h, 84%, 10 mins.
2g, 83%, 10 mins.
Br
Br
O
N
N
N
N
N
N
N
N
Me
Me
Bn
Bn
Bn
2k, 82%, 12 mins.
Br
Bn
RuCl3.3H2O
(5 mol %)
N
N
Bn
N
Bn
2l, 80%, 12 mins.
N
H
Me
2j, 86%, 12 mins.
2'a
(major, 62%)
H
Me
TBHP (2 eq)
MW, 110 oC
Br
1a
1'a
N
N
N
N
N
Cl
N
N
N
N
Me
N
Cl
Me
H
Not
observed
H
2a
2m, 81%, 13 mins.
2n, 77%, 13 mins.
(minor, 18%)
2o, 72%, 16 mins.
Br
Br
Scheme 4. Cross reaction between two different indoles
methods,16 we were interested to investigate the substrate
scope for their synthesis. To our delight, compounds 2' which
contain a wide range of substituents could be obtained in
moderate yields as summarized in scheme 5. The products of
these reactions were characterized by NMR spectroscopy as
well as X-ray crystallography (single crystal X-ray structure of
2b and 2'a, Figure 1).17
N
N
N
N
N
N
Cl
Br
Cl
Cl
2p, 78%, 18 mins.
Br
Cl
2q, 75%, 18 mins.
2r, 71%, 16 mins.
N
N
N
N
N
N
N
N
Br
Me
Me
2u
not formed
Br
Me
Me
2s, 75%, 16 mins.
2t, 72%, 16 mins.
Scheme 3. Substrate scope for the synthesis of BIMs (2). Reaction conditions: 1 (1.0
mmol), TMU (2.0 mmol, 232 mg), RuCl3.3H2O (5 mol %, 13 mg), TBHP (5.5M in decane,
2.0 mmol, 364 mg) at 110 oC under microwave irradiation. Products were purified by
column chromatography using silica gel (100-200 mesh) and yields are for the isolated
products.
Figure 1. X-ray structure of compound 2b and 2'a
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To find out the reaction mechanism, we carried out the obtained 11 % of 2a in case of BHT, whereas TEMPO produced
model reaction in presence of radical scavengers such as BHT, only 7 % of 2a. Therefore, we believe that the formation of
TEMPO under the optimized reaction condition to check the BIMs involved free radical route. We also noticed that use of
possibility of radical route. We noticed a substantial inhibition stoichiometric amount of catalyst in absence of TBHP
of the formation of 2a by both the radical scavengers and
produced no product, which confirms that TBHP acts more
than as an oxidant. We, therefore, propose a tentative
mechanism for the formation of 2 on the basis of our
experiments and relevant reports (Scheme 6).1a, 13a First, Ru(III)
removes an electron from the nitrogen of TMU, which
generates a radical cation [
converted to iminium ion [
substituted indole (1a) generating [
eliminates molecule of trimethylurea to produce
alkylideneindoleninium ion [ ]. This ion either can be attacked
A
]. In presence of TBHP, [
]. This ion is then attacked by N-
], which subsequently
A] gets
B
C
a
D
by another N-substituted indole (1a) or NH-indole (1'a, if cross
reaction is performed) furnishing 2a or 2'a respectively.
Conclusions
In conclusion, we have developed a microwave assisted
RuCl3.3H2O/TBHP mediated reaction of indoles with
tetramethylurea, which produced 3,3-bis(indolyl)methanes in
good to excellent yield with relatively shorter reaction time.
Moreover, unsymmetrical bis(indolyl)methanes can also be
synthesized in moderate yield by this method. The methylene
carbon of the product molecule is delivered by TMU. This is
the first report of TMU as a methylenating agent. Since a large
amount of TMU is obtained as industrial byproduct, their use
as the methylenating agent in the reaction made the
methodology more useful.
Experimental
Scheme 5. Substrate scope for the synthesis of unsymmetrical BIMs (2'). Reaction
General information
conditions: 1 (0.5 mmol), 1' (0.5 mmol), TMU (2.0 mmol, 232 mg), RuCl3.3H2O (5 mol %,
13 mg), TBHP (5.5M in decane, 2.0 mmol, 364 mg) at 110 oC under microwave All the commercially available reagents were used as received.
irradiation. Products were purified by column chromatography using silica gel (100-200
Melting points were determined in open capillary tubes with a
mesh) and yields are for the isolated products. The yields shown in the parenthesis are
Buchi-540 micro melting point apparatus and were uncorrected. I.R.
the amount of corresponding symmetrical BIMs of N-alkylindoles.
spectra were recorded on a Perkin-Elmer system 2000 FT-IR
spectrometer. Mass spectra (ESI-HRMS) were recorded on Agilent
Accurate-Mass Q-TOF LC/MS 6520. NMR spectra were recorded on
a Bruker Avance DPX-300 and -500 NMR spectrometer with TMS as
the internal standard at room temperature. Chemical shifts (δ) are
quoted in ppm and coupling constants (J) are measured in Hertz
(Hz). All the experiments were monitored by thin layer
chromatography (TLC) on pre-coated silica gel plates (Merck) and
visualized under UV lamp at 254 nm for UV active materials. Further
visualization was achieved by staining KMnO4 warming in a hot air
oven or by iodine vapor. Column chromatography was performed
on silica gel (100-200 mesh, Merck) using ethyl acetate/hexane as
eluent.
Microwave instrumentation
All microwave reactions were carried out in a Synthos 3000 (Anton
Paar) microwave reactor. The multitude microwave has a twin
magnetron (2.45 GHz) with maximum output power of 1400 W. The
Scheme 6. Tentative mechanism proposed for the reaction
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output power can be controlled in unpulsed control mode over 128.1, 125.3, 121.2, 119.4, 118.5, 114.3, 109.1, 40.7, 21.1,
whole power which is adjustable in 1 W increment. A 68xxx series 15.5; HRMS (ESI) exact mass calculated for C21H22N2 [M + H]+:
microprocessor system control is used to measure power, pressure, 303.1861; found: 303.1867.
time and temperature during the reaction. The temperature and
pressure were monitored throughout the reaction by an infrared Bis(1-ethyl-2-methyl-1H-indol-3-yl)methane (2d)18a
o
Brown solid; Yield 91 %, 300 mg; Mp = 98-100 oC; IR (KBr):
detector. The temperature can be measured from 0 to 280 C with
3082, 2917, 2856, 1622, 1385, 1210, 1066, 739 cm-1; 1H NMR
uncertainty ±1%. The pressure can be measured from 0 to 86 bar
with uncertainty ±0.2 bar. The MW power is initially set at 600 W
(500 MHz, CDCl3): δ 7.40 (d,
2H), 7.08 (t, = 7.0 Hz, 2H), 6.96-6.93 (m, 2H), 4.14 (s, 2H), 4.11
(q, = 7.2 Hz, 4H), 2.35 (s, 6H), 1.30 (t,
= 7.2 Hz, 6H); 13C NMR
J = 7.8 Hz, 2H), 7.23 (d, J = 8.1 Hz,
but during the course of the reaction, once the set temperature is
reached, the reactor automatically adjusts the power by lowering it.
J
J
J
(125 MHz, CDCl3): δ 135.4, 131.9, 128.3, 120.1, 118.5, 118.4,
110.4, 108.3, 37.6, 19.9, 15.4, 10.2; HRMS (ESI) exact mass
calculated for C23H26N2 [M + H]+: 331.2174; found: 331.2179.
Representative procedure for the synthesis of 2a
N-methylindole (1 mmol, 131 mg), TMU (2 mmol, 232 mg),
RuCl3.3H2O (5 mol %, 13 mg) and TBHP (5.5 M in decane, 2 mmol,
364 mg) were irradiated in a closed vessel inside a microwave
reactor at 110 ˚C for specified time. The progress of the reaction
was monitored by TLC. After completion, the reaction mixture was
cooled to room temperature and poured into water (10 mL). Then
extracted with ethyl acetate (2 x 10 mL) and dried over anhydrous
Na2SO4. Removed the solvent under reduced pressure and purified
the crude product by column chromatography (silica gel, 100-200
mesh; ethyl acetate/hexane as eluent) to obtain the desired
product 2a.
Bis(5-bromo-1-ethyl-1H-indol-3-yl)methane (2e)
White solid; Yield 87 %, 400 mg; Mp = 141-142 oC; IR (KBr):
1
3069, 2856, 1626, 1465, 1391, 1218, 988, 744 cm-1; H NMR
(500 MHz, CDCl3): δ 7.69 (d,
1H), 7.26 (d, = 1.8 Hz, 1H), 7.18 (d,
2H), 4.11 (s, 2H), 4.07 (q, = 7.3 Hz, 4H), 1.40 (t,
J
= 1.8 Hz, 2H), 7.28 (d,
= 8.5 Hz, 2H), 6.85 (s,
= 7.3 Hz, 6H);
J = 1.8 Hz,
J
J
J
J
13C NMR (125 MHz, CDCl3): δ 134.9, 129.6, 126.4, 124.1, 121.9,
113.5, 112.0, 110.7, 41.0, 20.9, 15.5; HRMS (ESI) exact mass
calculated for C21H20Br2N2 [M
459.0066.
+
H]+: 459.0071; found:
The representative procedure for the synthesis of 2'a
Bis(1-propyl-1H-indol-3-yl)methane (2f)
The procedure is same as above except in place of N-methylindole,
a mixture of N-methylindole (0.5 mmol) and NH-indole (0.5 mmol)
were taken.
Brown gummy solid; Yield 85 %, 280 mg; IR (CHCl3): 3077,
1
2913, 1640, 1394, 1212, 1118, 1054, 741 cm-1; H NMR (500
MHz, CDCl3): δ 7.61 (d,
7.21-7.17 (m, 2H), 7.07-7.04 (m, 2H), 6.83 (s, 2H), 4.22 (s, 2H),
3.98 (t, = 7.2 Hz, 4H ), 1.83-1.76 (m, 4H), 0.88 (t, = 7.3 Hz,
J = 7.9 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H),
Bis(1-methyl-1H-indol-3-yl)methane (2a)18
J
J
6H); 13C NMR (125 MHz, CDCl3): δ 136.4, 128.0, 126.1, 121.1,
119.4, 118.4, 114.0, 109.2, 47.8, 23.6, 21.1, 11.5; HRMS (ESI)
exact mass calculated for C23H26N2 [M + H]+: 331.2174; found:
331.2180.
Low melting red solid; Yield 85 %, 233 mg; IR (CHCl3): 3080,
2913, 1644, 1396, 1218, 1052 cm-1; 1H NMR (500 MHz, CDCl3):
δ 7.63 (d, J = 7.9 Hz, 2H), 7.29 (d, J = 8.2 Hz, 2H), 7.23-7.20 (m,
2H), 7.10-7.07 (m, 2H), 6.79 (s, 2H), 4.22 (s, 2H), 3.70 (s, 6H);
13C NMR (125 MHz, CDCl3): δ 137.1, 127.9, 126.9, 121.4, 119.3,
118.5, 114.3, 109.1, 32.6, 20.9; HRMS (ESI) exact mass
calculated for C19H18N2 [M + H]+: 275.1548; found: 275.1553.
Bis(5-bromo-1-propyl-1H-indol-3-yl)methane (2g)
White solid; Yield 83 %, 405 mg; Mp = 124-126 oC; IR (KBr):
3054, 2858, 1630, 1462, 1364, 1204, 1012, 738 cm-1; 1H NMR
Bis(1,2-dimethyl-1H-indol-3-yl)methane (2b)
o
Light red solid; Yield 88 %, 266 mg; Mp = 111-113 C; IR (KBr):
(500 MHz, CDCl3): δ 7.67 (d,
7.18 (d, = 8.7 Hz, 2H), 6.84 (s, 2H), 4.11 (s, 2H), 3.99 (t,
Hz, 4H ), 1.84-1.77 (m, 4H), 0.89 (t,
= 7.3 Hz, 6H); 13C NMR
J
= 1.5 Hz, 2H), 7.26-7.24 (m, 2H),
J
J
= 7.0
1
3102, 2926, 1622, 1376, 1210, 741 cm-1; H NMR (500 MHz,
J
(125 MHz, CDCl3): δ 135.2, 129.5, 127.2, 124.1, 121.9, 113.2,
111.9, 110.8, 48.0, 23.5, 21.0, 11.5; HRMS (ESI) exact mass
CDCl3): δ 7.42 (d, J = 7.8 Hz, 2H), 7.22-7.19 (m, 2H), 7.10-7.07
(m, 2H), 6.97-6.94 (m, 2H), 4.14 (s, 2H), 3.61 (s, 6H), 2.36 (s,
6H); 13C NMR (125 MHz, CDCl3): δ 136.5, 133.1, 132.6, 128.5,
128.3, 128.0, 120.2, 118.5, 118.4, 110.3, 108.3, 29.4, 19.9,
10.4; HRMS (ESI) exact mass calculated for C21H22N2 [M + H]+:
303.1861; found: 303.1856.
calculated for C23H24Br2N2 [M
487.0379.
+
H]+: 487.0384; found:
Bis(5-methoxy-1-methyl-1H-indol-3-yl)methane (2h)18b
White solid; Yield 84 %, 281 mg; Mp = 134-136 oC; IR (KBr):
3051, 2853, 1630, 1466, 1361, 1188, 1056, 743 cm-1; 1H NMR
Bis(1-ethyl-1H-indol-3-yl)methane (2c)18a
(500 MHz, CDCl3): δ 7.21 (d,
J = 6.6 Hz, 2H), 7.05 (d, J = 1.8 Hz,
Red gummy solid; Yield 93 %, 281 mg; IR (CHCl3): 3087, 2933,
1621, 1377, 1216, 1061, 744 cm-1; 1H NMR (500 MHz, CDCl3): δ
2H), 6.88 (d, = 6.2 Hz, 2H), 6.77 (s, 2H), 4.14 (s, 2H), 3.81 (s,
J
6H), 3.66 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 153.8, 132.8,
128.2, 127.6, 113.8, 111.6, 109.8, 101.2, 56.2, 32.7, 20.8;
HRMS (ESI) exact mass calculated for C21H22N2O2 [M + H]+:
335.1760; found: 335.1766.
7.63-7.61 (m, 2H), 7.32 (d,
7.09-7.06 (m, 2H), 6.86 (s, 2H), 4.23 (s, 2H), 4.09 (q,
4H), 1.40 (t,
= 7.2 Hz, 6H); 13C NMR (125 MHz, CDCl3): δ 136.1,
J
= 8.2 Hz, 2H), 7.22-7.19 (m, 2H),
J
= 7.2 Hz,
J
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3,3'-Methylenebis(1-ethyl-1H-indole-5-carbonitrile) (2i)18a
Brown solid; Yield 75 %, 264 mg; Mp = 139-141 oC; IR (KBr):
3056, 2842, 2226, 1621, 1442, 1364, 1201, 1011, 739 cm-1; 1H
Red gummy solid; Yield 77 %, 373 mg; IR (CHCl3): 3081, 2958,
1630, 1467, 1361, 1214, 1012, 739 cm-1; 1H NMR (500 MHz,
CDCl3): δ 7.68 (d, J = 1.8 Hz, 2H), 7.27-7.25 (m, 2H), 7.16 (d, J =
8.7 Hz, 2H), 6.85 (s, 2H), 5.98-5.90 (m, 2H), 5.19-5.17 (m, 2H),
5.02-4.99 (m, 2H), 4.65-4.64 (m, 4H), 4.12 (s, 2H); 13C NMR
(125 MHz, CDCl3): δ 135.1, 133.1, 129.4, 127.2, 124.2, 121.8,
117.1, 113.4, 112.1, 111.1, 48.7, 20.9; HRMS (ESI) exact mass
NMR (500 MHz, CDCl3): δ 7.88 (d,
8.7, 1.8 Hz, 2H), 7.36 (d, = 8.6 Hz, 2H), 6.99 (s, 2H), 4.22 (s,
2H), 4.16 (q, = 7.3 Hz, 4H), 1.45 (t,
= 7.3 Hz, 6H); 13C NMR
J = 1.8 Hz, 2H), 7.43 (dd, J =
J
J
J
(125 MHz, CDCl3): δ 137.8, 127.4, 127.2, 124.9, 124.4, 120.9,
114.6, 110.0, 101.6, 41.1, 21.0, 15.3; HRMS (ESI) exact mass
calculated for C23H20N4 [M + H]+: 353.1766; found: 353.1761.
calculated for C23H20Br2N2 [M
483.0068.
+
H]+: 483.0071; found:
Bis(1-benzyl-1H-indol-3-yl)methane (2j)18
Bis(1-(3-chlorobenzyl)-1H-indol-3-yl)methane (2o)
Off white solid; Yield 86 %, 366 mg; Mp = 131-132 oC; IR (KBr):
3109, 3052, 2856, 1620, 1369, 1216, 1035, 742 cm-1; 1H NMR
Brownish gummy solid; Yield 72 %, 356 mg; IR (KBr): 3074,
1
2831, 1624, 1471, 1359, 1213, 1146, 745 cm-1; H NMR (500
MHz, CDCl3): δ 7.64 (d, J = 7.8 Hz, 2H), 7.23-7.16 (m, 8H), 7.12-
(500 MHz, CDCl3): δ 7.63 (d,
7.17-7.14 (m, 2H), 7.08 (d,
4H), 4.26 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 137.9, 136.8,
128.6, 128.2, 127.4, 126.6, 126.5, 121.6, 119.5, 118.8, 114.8,
109.6, 49.8, 21.2; HRMS (ESI) exact mass calculated for
C31H26N2 [M + H]+: 427.2174; found: 427.2180.
J
= 7.9 Hz, 2H), 7.26-7.23 (m, 10H),
7.09 (m, 2H), 7.07 (m, 2H), 6.94-6.91 (m, 4H), 5.22 (s, 4H), 4.28
(s, 2H); 13C NMR (125 MHz, CDCl3): δ 139.9, 136.5, 134.4,
129.9, 128.1, 127.6, 126.5, 126.4, 124.6, 121.8, 119.5, 119.0,
114.8, 109.4, 49.2, 21.2; HRMS (ESI) exact mass calculated for
C31H24Cl2N2 [M + H]+: 495.1395; found: 495.1390.
J
= 7.2 Hz, 4H), 6.92 (s, 2H), 5.25 (s,
Bis(1-(4-chlorobenzyl)-1H-indol-3-yl)methane (2p)
o
Reddish solid; Yield 78 %, 386 mg; Mp = 121-123 C; IR (KBr):
Bis(1-benzyl-2-methyl-1H-indol-3-yl)methane (2k)
White solid; Yield 82 %, 372 mg; Mp = 129-131 oC; IR (KBr):
1
3074, 2856, 1590, 1472, 1364, 1184, 1092, 738 cm-1; H NMR
1
3104, 3056, 2849, 1622, 1366, 1201, 739 cm-1; H NMR (500
(500 MHz, CDCl3): δ 7.61 (d, J = 7.8 Hz, 2H), 7.23-7.20 (m, 5H),
MHz, CDCl3): δ 7.41 (d, J = 7.8 Hz, 2H), 7.27-7.16 (m, 7H), 7.08-
7.19-7.14 (m, 3H), 7.09-7.06 (m, 2H), 6.99-6.98 (m, 4H), 6.88 (s,
2H), 5.20 (s, 4H), 4.25 (s, 2H); 13C NMR (125 MHz, CDCl3): δ
136.7, 136.3, 133.2, 128.8, 128.2, 128.0, 127.8, 126.3, 121.8,
119.5, 119.0, 115.0, 109.5, 49.2, 21.2; HRMS (ESI) exact mass
7.03 (m, 3H), 6.97-6.94 (m, 2H), 6.90-6.89 (m, 4H), 5.32 (s, 4H),
4.21 (s, 2H), 2.36 (s, 6H); 13C NMR (125 MHz, CDCl3): δ 138.1,
136.3, 132.4, 128.6, 128.5, 128.1 (2C), 127.0, 125.7, 120.5,
118.7, 118.5, 111.0, 108.7, 46.2, 20.1, 10.5; HRMS (ESI) exact
mass calculated for C33H30N2 [M + H]+: 455.2487; found:
455.2491.
calculated for C31H24Cl2N2 [M
495.1398.
+
H]+: 495.1395; found:
Bis(5-bromo-1-(4-chlorobenzyl)-1H-indol-3-yl)methane (2q)
Brownish solid; Yield 75 %, 490 mg; Mp = 186-188 oC; IR (KBr):
Bis(1-benzyl-5-bromo-1H-indol-3-yl)methane (2l)
o
White shining solid; Yield 80 %, 467 mg; Mp = 174-176 C; IR
(KBr): 3114, 2855, 1612, 1468, 1354, 1192, 738 cm-1; 1H NMR
3087, 2962, 2837, 1634, 1468, 1374, 1184, 1147, 1093, 743
cm-1; 1H NMR (500 MHz, CDCl3): δ 7.66 (d,
7.24 (m, 4H), 7.22-7.20 (m, 2H), 7.04 (d,
J
= 1.7 Hz, 2H), 7.26-
(500 MHz, CDCl3): δ 7.68 (d,
J
= 1.7 Hz, 2H), 7.31-7.28 (m, 4H),
= 8.7 Hz, 2H),
J
= 8.7 Hz, 2H), 6.96-
7.26-7.24 (m, 2H), 7.22-7.20 (m, 2H), 7.09 (d,
J
6.94 (m, 4H), 6.91 (s, 2H), 5.18 (s, 4H), 4.13 (s, 2H); 13C NMR
(125 MHz, CDCl3): δ 135.6, 135.2, 133.3, 129.6, 128.9, 127.7,
127.4, 124.6, 122.0, 113.7, 112.3, 111.1, 49.3, 21.2; HRMS
(ESI) exact mass calculated for C31H22Br2Cl2N2 [M + H]+:
650.9605; found: 650.9609.
7.06-7.04 (m, 4H), 6.92 (s, 2H), 5.23 (s, 4H), 4.14 (s, 2H); 13C
NMR (125 MHz, CDCl3): δ 137.2, 135.5, 129.7, 128.8, 127.7,
127.6, 126.5, 124.5, 122.0, 113.8, 112.3, 111.2, 50.1, 21.2;
HRMS (ESI) exact mass calculated for C31H24Br2N2 [M + H]+:
583.0384; found: 583.0389.
Bis(1-allyl-1H-indol-3-yl)methane (2m)
Bis(1-(4-bromobenzyl)-1H-indol-3-yl)methane (2r)
Brown gummy solid; Yield 81 %, 264 mg; IR (CHCl3): 3084, Brown solid; Yield 71 %, 415 mg; Mp = 149-151 oC; IR (KBr):
1
2950, 2831, 1631, 1368, 1216, 1019, 744 cm-1; H NMR (500 3037, 2911, 2851, 1630, 1476, 1365, 1211, 1134, 1022, 743
MHz, CDCl3): δ 7.62 (d,
7.21-7.18 (m, 2H), 7.09-7.06 (m, 2H), 6.85 (s, 2H), 5.99-5.91 (m, 7.35 (m, 4H), 7.20-7.13 (m, 4H), 7.09-7.05 (m, 2H), 6.91 (d,
J = 7.9 Hz, 2H), 7.29 (d, J J = 7.8 Hz, 2H), 7.39-
= 8.2 Hz, 2H), cm-1; 1H NMR (500 MHz, CDCl3): δ 7.61 (d,
J
=
2H), 5.16-5.14 (m, 2H), 5.08-5.04 (m, 2H), 4.66-4.64 (m, 4H), 8.2 Hz, 4H), 6.86 (s, 2H), 5.17 (s, 4H), 4.24 (s, 2H); 13C NMR
4.23 (s, 2H); 13C NMR (125 MHz, CDCl3): δ 139.3, 136.5, 133.7, (125 MHz, CDCl3): δ 136.8, 136.7, 131.8, 128.3, 128.2, 126.3,
126.0, 121.4, 119.4, 118.7, 116.9, 114.5, 114.1, 109.5, 48.6, 121.8, 121.3, 119.5, 119.0, 115.0, 109.5, 49.2, 21.2; HRMS (ESI)
22.7; HRMS (ESI) exact mass calculated for C23H22N2 [M + H]+: exact mass calculated for C31H24Br2N2 [M + H]+: 583.0384;
327.1861; found: 327.1856.
found: 583.0389.
Bis(1-allyl-5-bromo-1H-indol-3-yl)methane (2n)
Bis(1-(3-bromobenzyl)-1H-indol-3-yl)methane (2s)
6 | J. Name., 2012, 00, 1-3
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Off white solid; Yield 75 %, 438 mg; Mp = 104-106 oC; IR (KBr): 3-((1H-indol-3-yl)methyl)-1,2-dimethyl-1H-indole (2'd)
White solid; Yield 58 %, 159 mg; Mp = 176-178 oC (dec); IR
(KBr): 3417, 3056, 2927, 1661, 1396, 1210, 742 cm-1; 1H NMR
3061, 2936, 2854, 1620, 1472, 1368, 1201, 1172, 1016, 744
cm-1; 1H NMR (500 MHz, CDCl3): δ 7.63 (d,
J
= 7.8 Hz, 2H), 7.36
(d,
J = 7.9 Hz, 2H), 7.21-7.15 (m, 6H), 7.13-7.08 (m, 4H), 6.97-
(500 MHz, CDCl3): δ 7.68-7.66 (m, 2H), 7.48 (d, J = 7.9 Hz, 1H),
6.95 (m, 2H), 6.88 (s, 2H), 5.20 (s, 4H), 4.26 (s, 2H); 13C NMR
(125 MHz, CDCl3): δ 140.2, 136.7, 130.6, 130.3, 129.6, 128.2,
126.3, 125.2, 122.8, 121.9, 119.5, 119.1, 115.1, 109.4, 49.2,
21.2; HRMS (ESI) exact mass calculated for C31H24Br2N2 [M +
H]+: 583.0384; found: 583.0378.
7.27-7.24 (m, 2H), 7.18-7.09 (m, 3H), 7.02-6.99 (m, 1H), 6.62
(m, 1H), 4.17 (s, 2H), 3.65 (s, 3H), 2.36 (s, 3H); 13C NMR (125
MHz, CDCl3): δ 136.6, 136.4, 132.2, 128.0, 127.3, 122.0, 121.8,
120.4, 119.1, 118.8, 118.6, 118.5, 116.4, 110.0, 109.5, 108.4,
29.5, 20.2, 10.3; HRMS (ESI) exact mass calculated for C19H18N2
[M + H]+: 275.1548; found: 275.1543.
Bis(1-(4-methylbenzyl)-1H-indol-3-yl)methane (2t)
Brownish solid; Yield 72 %, 327 mg; Mp = 99-101 oC; IR (CHCl3): 2-Methyl-3-((1-methyl-1H-indol-3-yl)methyl)-1H-indole (2'e)
1
3074, 2932, 2837, 1622, 1462, 1360, 1221, 1002, 743 cm-1; H
Off-white solid; Yield 66 %, 181 mg; Mp = 201-203 oC; IR (KBr):
3402, 3055, 2926, 2856, 1682, 1470, 1327, 1013, 742 cm-1; 1H
NMR (500 MHz, CDCl3): δ 7.61 (d, J = 7.9 Hz, 2H), 7.25-7.18 (m,
3H), 7.15-7.11 (m, 2H), 7.10-7.04 (m, 6H), 6.97-6.95 (m, 3H),
6.88 (s, 2H), 5.18 (s, 4H), 4.24 (s, 2H), 2.29 (s, 6H); 13C NMR
(125 MHz, CDCl3): δ 137.0, 136.8, 134.8, 129.3 (2C), 126.7,
126.4 (2C), 121.5, 120.2, 119.4, 118.7, 114.7, 109.6, 49.6, 21.2,
21.0; HRMS (ESI) exact mass calculated for C33H30N2 [M - H]+:
453.2331; found: 453.2337.
NMR (300 MHz, CDCl3): δ 7.81 (bs, 1H), 7.71 (d,
J = 7.8 Hz, 1H),
7.50 (d, J = 7.8 Hz, 1H), 7.31-7.22 (m, 3H), 7.17-7.11 (m, 2H),
7.08-7.03 (m, 1H), 6.58 (s, 1H), 4.18 (s, 2H), 3.65 (s, 3H), 2.41
(s, 3H); 13C NMR (125 MHz, CDCl3): δ 137.2, 137.1, 135.3,
127.7, 126.8, 125.0, 121.3, 120.8, 119.0, 118.9, 118.6, 118.5,
114.6, 112.2, 110.0, 109.0, 32.5, 19.7, 11.7; HRMS (ESI) exact
mass calculated for C19H18N2 [M + H]+: 275.1548; found:
275.1553.
3-((1H-indol-3-yl)methyl)-1-methyl-1H-indole (2'a)
White solid; Yield 62 %, 161 mg; Mp = 181-182 oC; IR (KBr):
3408, 3045, 2929, 1615, 1456, 1325, 1085, 742 cm-1; 1H NMR 5-Bromo-3-((1-methyl-1H-indol-3-yl)methyl)-1H-indole (2'f)
o
(500 MHz, CDCl3): δ 7.81 (bs, 1H), 7.63-7.60 (m, 2H), 7.32 (d,
J
Brown solid; Yield 65 %, 220 mg; Mp = 211-213 C; IR (CHCl3):
3413, 3035, 2923, 1624, 1461, 1376, 1211, 1089, 744 cm-1; 1H
= 8.2 Hz, 1H), 7.28 (d, J = 8.2 Hz, 1H), 7.23-7.16 (m, 2H), 7.10-
7.06 (m, 2H), 6.89 (m, 1H), 6.76 (s, 1H), 4.22 (s, 2H), 3.67 (s,
3H); 13C NMR (125 MHz, CDCl3): δ 137.1, 136.4, 127.9, 127.5,
127.0, 122.1, 121.8, 121.4, 119.2 (2C), 119.1, 118.5, 115.8,
114.1, 111.0, 109.1, 32.5, 21.0; HRMS (ESI) exact mass
calculated for C18H16N2 [M + H]+: 261.1392; found: 261.1385.
NMR (500 MHz, CDCl3): δ 7.90 (bs, 1H), 7.75 (d, J = 1.8 Hz, 1H),
7.58-7.56 (m, 1H), 7.30-7.28 (m, 1H), 7.25-7.19 (m, 3H), 7.09-
7.06 (m, 1H), 6.92 (m, 1H), 6.76 (s, 1H), 4.17 (s, 2H), 3.70 (s,
3H); 13C NMR (125 MHz, CDCl3): δ 137.2, 135.0, 129.3, 127.7,
126.9, 124.7, 123.4, 121.8, 121.5, 119.2, 118.6, 115.6, 113.5,
112.5, 109.2, 32.6, 21.0; HRMS (ESI) exact mass calculated for
C18H15BrN2 [M + H]+: 339.0497; found: 339.0499.
3-((1H-indol-3-yl)methyl)-1-ethyl-1H-indole (2'b)
Brownish solid; Yield 64 %, 175 mg; Mp = 184-186 oC; IR (KBr):
1
3411, 3058, 2917, 1614, 1336, 1092, 744 cm-1; H NMR (500 1-Ethyl-3-((2-methyl-1H-indol-3-yl)methyl)-1H-indole (2'g)
MHz, CDCl3): δ 7.77 (bs, 1H), 7.62-7.59 (m, 2H), 7.31-7.29 (m,
Gummy solid; Yield 64 %, 184 mg; IR (CHCl3): 3401, 3081, 2922,
1
1641, 1470, 1377, 1216, 1042, 743 cm-1; H NMR (500 MHz,
2H), 7.21-7.15 (m, 2H), 7.10-7.05 (m, 2H), 6.86 (s, 1H), 6.82 (s,
1H), 4.22 (s, 2H), 4.04 (q, J = 7.3 Hz, 2H), 1.36 (t, J = 7.3 Hz, 3H);
CDCl3): δ 7.77 (bs, 1H), 7.68-7.66 (m, 1H), 7.47 (d,
1H), 7.30-7.27 (m, 2H), 7.21-7.18 (m, 1H), 7.12-7.08 (m, 2H),
7.03-7.00 (m, 1H), 6.62 (s, 1H), 4.15 (s, 2H), 4.01 (q, = 7.3 Hz,
2H), 2.38 (s, 3H), 1.33 (t,
= 7.3 Hz, 3H); 13C NMR (125 MHz,
J = 7.8 Hz,
13C NMR (125 MHz, CDCl3): δ 136.4, 136.1, 128.0, 127.5, 125.2,
122.2, 121.8, 121.2, 119.4, 119.2, 119.1, 118.5, 115.8, 114.1,
111.0, 109.2, 40.7, 21.1, 15.5; HRMS (ESI) exact mass
calculated for C19H18N2 [M + H]+: 275.1548; found: 275.1554.
J
J
CDCl3): δ 137.1, 136.1, 135.2, 129.0, 127.9, 125.1, 121.2, 120.7,
119.0 (2C), 118.6, 118.4, 114.6, 110.5, 110.0, 109.1, 40.7, 19.8,
15.5, 11.8; HRMS (ESI) exact mass calculated for C20H20N2 [M +
H]+: 289.1705; found: 289.1702.
3-((1H-indol-3-yl)methyl)-1-propyl-1H-indole (2'c)
o
Light red solid; Yield 68 %, 196 mg; Mp = 191-193 C; IR (KBr):
1
3408, 3048, 2913, 1614, 1461, 1375, 742 cm-1; H NMR (500
5-Bromo-3-((1-ethyl-1H-indol-3-yl)methyl)-1H-indole (2'h)
MHz, CDCl3): δ 7.91 (bs, 1H), 7.63-7.60 (m, 2H), 7.36-7.30 (m,
2H), 7.21-7.17 (m, 2H), 7.10-7.05 (m, 2H), 6.93-6.92 (m, 1H), White solid; Yield 59 %, 208 mg; Mp = 197-199 oC; IR (KBr):
6.85 (s, 1H), 4.23 (s, 2H), 3.99 (t,
2H), 0.89 (t,
= 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 136.4 NMR (500 MHz, CDCl3): δ 7.88 (bs, 1H), 7.74 (d,
(2C), 128.0, 127.6, 126.1, 122.2, 121.8, 121.2, 119.3, 119.2, 7.58-7.56 (m, 1H), 7.32 (d, = 8.2 Hz, 1H), 7.26-7.24 (m, 1H),
119.1, 118.4, 115.9, 113.8, 111.0, 109.3, 47.8, 23.6, 21.1, 11.5; 7.22-7.19 (m, 2H), 7.08-7.05 (m, 1H), 6.91 (d,
HRMS (ESI) exact mass calculated for C20H20N2 [M + H]+: 6.84 (s, 1H), 4.17 (d,
= 1.0 Hz, 2H), 4.09 (q,
J
= 7.0 Hz, 2H), 1.84-1.77 (m, 3417, 3058, 2911, 1617, 1460, 1375, 1210, 1092, 744 cm-1; 1H
J
J
= 1.0 Hz, 1H),
J
J
J
= 1.2 Hz, 1H),
= 7.2 Hz, 2H),
J
289.1705; found: 289.1701.
1.40 (t,
J
= 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 136.2,
135.0, 129.3, 127.9, 125.2, 124.7, 123.4, 121.8, 121.3, 119.3,
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ARTICLE
Journal Name
118.6, 115.6, 113.5, 112.4, 109.2, 40.7, 21.0, 15.5; HRMS (ESI) White solid; Yield 58 %, 195 mg; Mp = 161-163 oC; IR (KBr):
exact mass calculated for C19H17BrN2 [M + H]+: 353.0653; 3407, 3046, 2927, 1603, 1458, 1330, 1236, 752 cm-1; 1H NMR
found: 353.0647.
(500 MHz, CDCl3): δ 8.03 (bs, 1H), 7.60 (d, J = 7.8 Hz, 1H), 7.48-
7.44 (m, 3H), 7.33-7.29 (m, 3H), 7.25-7.16 (m, 3H), 7.15-7.12
(m, 1H), 7.08-7.05 (m, 1H), 7.01-6.98 (m, 1H), 6.47 (s, 1H), 4.25
2-Methyl-3-((1-propyl-1H-indol-3-yl)methyl)-1H-indole (2'i)
o
White solid; Yield 68 %, 205 mg; Mp = 177-179 C; IR (CHCl3):
(d, J
= 0.9 Hz, 2H), 3.52 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
137.2, 136.0, 134.7, 132.9, 129.6, 128.9, 127.7, 127.6, 127.2,
122.3, 121.4, 119.7, 119.6, 119.0, 118.5, 114.6, 111.5, 110.7,
109.1, 32.6, 20.6; HRMS (ESI) exact mass calculated for
C24H20N2 [M + H]+: 337.1705; found: 337.1703.
3405, 3054, 2927, 1615, 1464, 1366, 1156, 740 cm-1; 1H NMR
(300 MHz, CDCl3): δ 7.84 (bs, 1H), 7.70 (d,
(d, = 7.2 Hz, 1H), 7.33-7.20 (m, 3H), 7.15-7.02 (m, 3H), 6.66 (s,
1H), 4.19 (s, 2H), 3.95 (t, = 7.2 Hz, 2H), 2.40 (s, 3H), 1.81-1.74
(m, 2H), 0.88 (t,
= 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ
J = 8.7 Hz, 1H), 7.50
J
J
J
1-Ethyl-3-((2-phenyl-1H-indol-3-yl)methyl)-1H-indole (2'n)
White solid; Yield 61 %, 214 mg; Mp = 167-169 oC; IR (KBr):
3402, 3048, 2923, 1608, 1456, 1336, 1228, 752 cm-1; 1H NMR
137.1, 136.4, 135.2, 129.0, 128.8, 125.9, 125.0, 121.1, 120.7,
119.0 (2C), 118.6, 118.4, 114.3, 110.0, 109.3, 47.8, 23.5, 19.9,
11.5; HRMS (ESI) exact mass calculated for C21H22N2 [M + H]+:
303.1861; found: 303.1864.
(500 MHz, CDCl3): δ 8.10 (bs, 1H), 7.67 (d, J = 7.9 Hz, 1H), 7.55-
7.52 (m, 3H), 7.40-7.36 (m, 3H), 7.32-7.28 (m, 2H), 7.25-7.19
(m, 2H), 7.14-7.11 (m, 1H), 7.08-7.05 (m, 1H), 6.61 (s, 1H), 4.32
5-Bromo-3-((1-propyl-1H-indol-3-yl)methyl)-1H-indole (2'j)
o
Pale yellow solid; Yield 60 %, 220 mg; Mp = 188-190 C (dec);
(d, J = 1.2 Hz, 2H), 3.98 (q, J = 7.3 Hz, 2H), 1.29 (t, J = 7.3 Hz,
3H); 13C NMR (125 MHz, CDCl3): δ 136.2, 136.0, 134.7, 132.9,
129.7, 128.9, 127.8, 127.6, 127.5, 125.5, 122.2, 121.3, 119.8,
119.6, 119.1, 118.5, 114.6, 111.6, 110.7, 109.2, 40.7, 20.6,
15.5; HRMS (ESI) exact mass calculated for C25H22N2 [M + H]+:
351.1861; found: 351.1865.
IR (CHCl3): 3410, 3058, 2919, 1624, 1473, 1359, 1201, 1081,
742 cm-1; 1H NMR (500 MHz, CDCl3): δ 7.90 (bs, 1H), 7.74 (m,
1H), 7.57 (d,
(m, 1H), 7.21-7.18 (m, 2H), 7.08-7.05 (m, 1H), 6.92 (m, 1H),
6.84 (s, 1H), 4.17 (s, 2H), 4.00 (t, = 7.0 Hz, 2H), 1.85-1.78 (m,
2H), 0.89 (t,
= 7.3 Hz, 3H); 13C NMR (125 MHz, CDCl3): δ 136.5,
J = 7.8 Hz, 1H), 7.32 (d, J = 8.2 Hz, 1H), 7.26-7.25
J
J
2-phenyl-3-((1-propyl-1H-indol-3-yl)methyl)-1H-indole (2'o)
White solid; Yield 63 %, 229 mg; Mp = 185-187 oC; IR (KBr):
3407, 3043, 2921, 2855, 1611, 1447, 1330, 1221, 750 cm-1; 1H
135.0, 129.3, 127.8, 126.1, 125.3, 124.6, 123.4, 121.9, 121.3,
119.3, 118.5, 115.6, 113.2, 112.4, 109.4, 47.8, 23.5, 21.1, 11.5;
HRMS (ESI) exact mass calculated for C20H19BrN2 [M + H]+:
367.0810; found: 367.0815.
NMR (300 MHz, CDCl3): δ 8.19 (bs, 1H), 7.74 (d,
7.62-7.60 (m, 3H), 7.46-7.37 (m, 5H), 7.32-7.11 (m, 4H), 6.67 (s,
1H), 4.40 (s, 2H), 3.95 (t, = 7.2 Hz, 2H), 1.83-1.71 (m, 2H), 0.86
J = 7.6 Hz, 1H),
J
1-Benzyl-3-((2-methyl-1H-indol-3-yl)methyl)-1H-indole (2'k)
o
White solid; Yield 55 %, 193 mg; Mp = 222-224 C; IR (CHCl3):
3405, 3056, 2924, 1619, 1465, 1332, 1172, 741 cm-1; 1H NMR
(t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3): δ 136.5, 136.0,
134.7, 132.9, 129.7, 129.0, 128.9, 127.8, 127.6, 127.5, 126.3,
122.2, 121.2, 119.7, 119.5, 119.1, 118.4, 114.3, 111.5, 110.7,
109.3, 47.7, 23.4, 20.6, 11.4; HRMS (ESI) exact mass calculated
for C26H24N2 [M + H]+: 365.2018; found: 365.2024.
(500 MHz, CDCl3): δ 7.79 (bs, 1H), 7.66 (d,
J = 7.8 Hz, 1H), 7.46
(d, = 7.8 Hz, 1H), 7.26-7.06 (m, 8H), 7.01-6.96 (m, 3H), 6.70 (s,
J
1H), 5.16 (s, 2H), 4.17 (s, 2H), 2.37 (s, 3H); 13C NMR (125 MHz,
CDCl3): δ 137.4, 136.7, 135.2, 128.7, 128.5, 128.1, 127.5, 126.5,
126.4, 124.9, 121.8, 121.5, 120.7, 119.5, 119.0, 118.8, 118.6,
115.2, 112.2, 110.0, 109.8, 109.6, 49.7, 19.9, 11.8; HRMS (ESI)
exact mass calculated for C25H22N2 [M + H]+: 351.1861; found:
351.1866.
Acknowledgements
MLD is thankful to Science and Engineering Research Board
(SERB), India (Grant No. SB/FT/CS-073/2014) for the financial
support under Fast Track Scheme. PKB is thankful to DST,
India, (Grant No. SB/FT/CS-100/2012) for the financial support.
The authors acknowledge Dr. Ranjit Thakuria, Dept. of
Chemistry, Gauhati University for X-ray structure analysis.
1-Benzyl-3-((5-bromo-1H-indol-3-yl)methyl)-1H-indole (2'l)
o
White solid; Yield 54 %, 224 mg; Mp = 210-212 C; IR (CHCl3):
3420, 3030, 2925, 1614, 1464, 1333, 1092, 741 cm-1; 1H NMR
(500 MHz, CDCl3): δ 7.90 (bs, 1H), 7.72 (s, 1H), 7.58 (d,
Hz, 1H), 7.27-7.23 (m, 5H), 7.18-7.17 (m, 2H), 7.07 (d,
J
J
= 7.8
= 7.0
Notes and references
Hz, 3H), 6.92 (s, 1H), 6.87 (s, 1H), 5.23 (s, 2H), 4.18 (s, 2H); 13C
NMR (125 MHz, CDCl3): δ 137.7, 136.8, 135.0, 129.2, 128.7,
128.0, 127.4, 126.6, 126.4, 124.7, 123.4, 121.8, 121.7, 119.3,
118.9, 115.3, 114.1, 112.5, 112.4, 109.7, 49.8, 21.2; HRMS (ESI)
exact mass calculated for C24H19BrN2 [M + H]+: 415.0810;
found: 415.0812.
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8 | J. Name., 2012, 00, 1-3
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J. Name., 2013, 00, 1-3 | 9
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