One-Pot Approach for the Synthesis of Bis-indole-1,4-disubstituted-1,2,3-triazoles

Article abstract of DOI:10.1021/acs.joc.8b02056

A new strategy for the synthesis of bis-indoletriazoles was developed using a sequential one-pot four-step procedure via I₂ and H₂SO₄-SiO₂ catalyzed Friedel-Crafts reactions of indole with aldehyde followed by N-alkylation with propargyl bromide, azidation, and copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). The reaction proceeded smoothly at room temperature in a short time, and a series of bis-indoletriazoles were obtained in good to excellent yields proving the generality of this one-pot methodology.

Full text of DOI:10.1021/acs.joc.8b02056

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Article
One pot approach for the synthesis of bis-
indole-1,4-disubstituted-1,2,3-triazoles
Natthiya Saehlim, Teerapich Kasemsuk, Uthaiwan Sirion, and Rungnapha Saeeng
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02056 • Publication Date (Web): 09 Oct 2018
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One pot approach for the synthesis of bis-indole-1,4-disubstituted-
1,2,3-triazoles
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Natthiya Saehlim†, Teerapich Kasemsuk‡, Uthaiwan Sirion†, Rungnapha
Saeeng*,†
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†Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of
Science, Burapha University, Sangesook, Chonburi 20131, Thailand
‡Department of Chemistry, Faculty of Science and Technology, RambhaiBarni Rajabhat
University, Chanthaburi, 22000, Thailand
*Correspondence: rungnaph@buu.ac.th
Abstract: A new strategy for the synthesis of bis-indoletriazoles was developed using a
sequential one-pot four-step procedure via I2 and H2SO4-SiO2 catalyzed Friedel-Crafts
reactions of indole with aldehyde followed by N-alkylation with propargyl bromide, azidation
and copper(I)-catalyzed azide alkyne cycloaddition (CuAAC). The reaction proceeded
smoothly at room temperature in a short time and a series of bis-indoletriazoles were obtained
in good to excellent yields proving the generality of this one-pot methodology.
Key words: Bis-indoletriazoles; Friedel-Crafts; CuAAC; One-pot
Introduction
Indole and triazole are important structural ring systems in pharmacological and
agrochemical compounds with various biological properties.1 Recently, bis-indole has received
considerable attention in medicinal chemistry as a main structural scaffold of bioactive natural
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products and synthetic drugs.2 Combination of indole or bis-indole and triazole into a single
compound for improving the biological efficacy or libraries of analogues for structure-activity
studies has been reported.3 These synthetic compounds exhibited a broad spectrum of
biological activities including antitubercular, anti-adipogenic, antibacterial and anticancer
activities (Figure 1).4-8
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Figure 1 Structure of bioactive compounds containing indole and triazole moieties
Despite the structural diversity and the variety of biological activities observed in
indoletriazole compounds, no convenient approach to the synthesis has been disclosed. The
previous synthesis reported by Perumal3 employed separated steps for their preparation which
are both time and cost consuming. Therefore, this work aimed to develop an efficient strategy
to complete an entire multi-step sequence in a single pot for the synthesis of bis-indoletriazoles
eliminating the need for work-up and product isolation between successive synthetic steps.
The synthesis of bis-indole-1,4-disubstituted-1,2,3-triazoles derivatives was designed
via Friedel-Crafts reactions, N-propargylation, azidation and the CuAAC reaction as a
sequential one-pot four-step reaction resulting in a high-yielding, scalable, and convergent
approach.
Results and Discussion
Firstly a possible one-pot three-step method was investigated for preparing bisindole-
triazole by screening Brønsted and Lewis acids as catalysts for Friedel-Crafts reactions of
indole 1a (2.2 equiv.) and p-chlorobenzaldehyde 2a in acetonitrile for in situ generation of
bisindole (Table 1). Then the N-propargylation step was carried out with propargyl bromide for
1 h using KOH as a base in the presence of acetonitrile to give products in high yield.
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Changing to other bases such as NaOH or NaH gave a low yield of product. In the same pot,
CuAAC reaction of the resulting N-propargylindole with benzyl azide for 1 h at room
temperature was carried out to obtain product 3a.
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Table 1. Optimization Studies for the synthesis of 3a via a one-pot three-step reaction.
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Cl
O
Acid cat.,
I)
CH3CN, Time1
H
+
II) KOH, propargyl bromide, rt, 1h
III) BnN3, CuI, Et3N, rt, 1h
N
Cl
H
N
N
N
N
N
N
N
N
1a
2a
3a
Entry
1
Acid cat. (equiv)
I2 (0.2)
Time1 (min)
Yield (%)a
20
20
58
23
48
90
66
95
98
39
82
58
2
ZnCl2 (0.2)
3
FeCl3 (0.2)
24 (h)
30
4
Bi(OTf)3 (0.2)
5b
6b
7b
8b
9b
10c
H2SO4-SiO2
20
Amberlyst 15
60
H2SO4-SiO2 /I2 (0.15)
H2SO4-SiO2 /ZnCl2 (0.15)
H2SO4-SiO2 /FeCl3 (0.15)
KHSO4 (1.0)
15
30
15
60
aReaction conditions: 1a (0.44 mmol), 2a (0.2 mmol), KOH (1.9mmol), CuI (0.06mmol), propargyl bromide
(0.6 mmol), Et3N (0.6 mmol), BnN3 (0.6 mmol) and CH3CN (0.6 mL)
bAmount of acid catalyst (H2SO4-SiO2 or Amberlyst 15) = 20 mg
cUsing KHSO4 in MeOH (Perumal's conditions)3, no reaction was observed in the second step.
In the screening of acid and Lewis acid in Friedel-Crafts step,9 molecular iodine (I2)
was initially investigated and the first step reaction was completed within 20 minutes affording
the desired product 3a in 58% yield after N-propargylation and click reactions (Table 1, entry
1). Using ZnCl2, FeCl3 or H2SO4-SiO219 as catalyst, low to moderate yields of product were
obtained (entries 2, 3 and 5). Changing the catalyst to Bi(OTf)3 and Amberlyst 15, the yield of
3a was increased to 90-95% (entries 4 and 6), however, the reaction with Amberlyst 15
required longer reaction times. Using H2SO4 supported on Silica-gel mixed with 15mol %
Lewis acid had an improved the reaction efficiency compared with the reaction without H2SO4-
SiO2 (entries 5, and 7–9). H2SO4-SiO2/I2 was found to be the most effective catalyst producing
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3a with a 98% yield in a short reaction time (entry 7). On the basis of these findings, entry 7
was selected as an optimal condition for synthesizing other analogues. It should be noted that,
the reaction failed to give the desired product in our one pot procedure when employing
Perumal’s conditions (KHSO4 as Lewis acid in MeOH)3. Applying KHSO4 as Lewis acid to
our one pot process gave 58% yield of product. Employing aliphatic aldehydes such as
propanal as the substrate instead of aromatic aldehydes under the conditions in entry 7, the
reaction gave 28% yield of product.
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With the optimized reaction conditions, a range of aromatic aldehydes and alkyl azides
were investigated. The results are summarized in Table 2, and a variety of aldehyde derivatives
2a-2e bearing either electron-donating groups such as 4-methoxy and electron-withdrawing
groups such as 4-chloro, 4-fluoro and 4-nitro at the para position of benzaldehyde gave the
desired products 3a-3e in 17−98% yields. Benzaldehyde 2b, 4-Cl-benzaldehydes 2a and 4-F-
benzaldehydes 2c gave excellent yields of bisindole-triazole products. Electron-donating
groups (p-methoxybenzaldehyde) exhibited a slightly lower reactivity in the Friedel-Crafts step
to afford 3d in 78% yield after stirring for 60 min. In contrast the strong functionalized
electron-deficient aldehyde 2e was smoothly reacted with indole 1a in the first step (with
observation on TLC) but gave low reactivity with propargyl bromide in the N-propargylation
step which led to 3e in poor yield.
A variety of organoazides bearing substituted benzyl, ether and esters functionalized
with alkyl, long chain aliphatic alkyl and tetra-O-acetyl-glucosyl groups were investigated and
the reactions generally proceeded smoothly, affording the corresponding products 3f-3r in
good to excellent yields. With these successful results for the one-pot three-step Friedel-Crafts
N-propargylation and CuAAC reactions for the synthesis of bis-indole-1,4-disubstituted-1,2,3-
triazole derivatives, the next step was to extend the procedure to a one-pot four-step reaction.
that can be better utilizing the reactions by reduce process in preparation the exposure-azides
by in situ preparation from corresponding alkyl halides and sodium azide in the reactor.10-15
The results are shown in Table 3.
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Table 2 The range of aldehydes and alkyl azides studied..
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Table 3. Optimization Studies for the synthesis of 4a via the one-pot four-step reaction
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The optimal conditions for the one-pot four-step synthesis of bisindoletriazole was
studied and it was found that including the additional step of azidation required the solvent to
be changed to DMF in the final step. DMF proved to be the best choice over acetonitrile, THF,
water and PEG-400, providing a high yield of product in a short reaction time. Moreover,
using alkyl halide in the azidation step was found to give yields of bisindoletriazole products
4a-4f higher than alkyl mesylate as shown in Table 3.
A range of aldehydes, indoles and alkyl halides were examined using the one-pot four-
step reaction and the results are summarized in Table 4. Using benzyl bromide in the azidation
step, a variety of substituted benzaldehydes were investigated and they gave just as good yields
of benzyltriazole-bisindoles 4a and 4i-4l as the one-pot three-step method in Table 1 except
nitrobenzaldehyde 2e.
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Table4. Range of aldehydes, indoles and alkyl halides studied.
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Next the a range of substituted methoxy- and fluoro-benzaldehydes were studied
together with a number of substituted benzyl bromides and compounds 4m-4s were obtained in
high yields. Using aliphatic bromide in the azidation step such as n-butyl and n-octyl bromide,
compounds 4t-4y were produced in moderate to high yields. Fluoroindole and Methoxyindole
were also investigated and performed well to yield the corresponding products 4z-4cc in good
to excellent yields under the one-pot conditions.
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Scheme 1. One-pot four-step synthesis of 5 using 5-hydroxyindole
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Scheme 2. One-pot four-step synthesis of 7 using terephthalaldehyde
Furthermore, the one-pot four-step reaction is applicable for the synthesis of bis-
indole tetra-triazoles and tetraindole-tetratriazole derivatives16-18 (Schemes 1 and 2). The
reaction of p-chlorobenzaldehyde 2a and 5-hydroxyindole 1d smoothly proceeded by using the
one-pot procedure to give 5 in good yields. When indole was treated with terephthalaldehyde
under the optimized conditions, tetraindole-tetratriazole 7 was obtained in good yields proving
the efficiency of the one-pot method.
Conclusions
An efficient protocol was developed for the sequential one-pot four-step synthesis of
bis-indole-1,4-disubstituted-1,2,3-triazoles from Friedel-Crafts reactions using H2SO4-SiO2/I2
as a Lewis acid catalyst, N-propargylation and azides generated in situ from alkyl halides and
sodium azide followed by the final step click reaction. The reactions gave high yields of
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product under mild conditions and are compatible with many functional groups, which can
save time and cost and only requires chromatographic purification of the final product, making
this process even more user friendly and safe.
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Experimental section
General information: All chemicals were purchased from commercial sources and used
without further purification. H and 13C{1H} NMR spectra were recorded on a BRUKER
1
AVANC 400 and 100 MHz instrument. All spectra were measured in CDCl3 solvent and
chemical shifts are reported as δ values in parts per million (ppm) relative to tetramethylsilane
(δ 0.00 ppm) or CDCl3 (δ(1H), 7.26; δ(13C), 77.0 ppm) as an internal standard. Data are
reported as follows; chemical shift (multiplicity, integrated intensity or assignment, coupling
constants in Hz, assignment). High-resolution mass spectra (HRMS) data were obtained with a
Finnigan MAT 95. Infrared spectra were determined on a PERKIN ELMER FT/IR-2000S
spectrophotometer and are reported in wave number (cm−1). Analytical thin-layer
chromatrography (TLC) was conducted on precoated TLC plates; silica gel 60F-254 [E. Merck,
Darmstadt, Germany]. Silica gel columns for open-column chromatrography utilized silica gel
60 PF254 [E. Merck, Darmstadt, Germany]. Melting points were measured using a Melting
point apparatus (Griffin) and are uncorrected. Sulphuric acid immobilized on silica gel
(H2SO4–SiO2) were prepared according to the literature procedure18.
General procedure for one-pot three-step bis-indole triazoles derivatives: For the first step,
a stirred solution of indole 1(1.1 mmol) in CH3CN (1 mL) was mixed with the aldehyde 2(0.5
mmol). Then I2 powder (9.5 mg, 0.075 mmol) and H2SO4-SiO2 (20 mg) was added while the
stirring was continued at room temperature. TLC showed the conversion was complete. In the
second step KOH (266.5 mg, 4.75 mmol) and propargyl bromide (0.1 mL, 1.5 mmol) was
added at room temperature and the stirring was continued for 1 h. The reaction mixture was
filtered to remove salt and the solvent of the filtrate was evaporated to dryness. The reaction
mixture was then re-dissolved in CH3CN (1 mL). Finally, alkyl azide (1.5 mmol), CuI (33.3
mg, 0.175 mmol) and Et3N (0.2 mL, 1.5 mmol) was added to the reaction mixture and stirred at
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room temperature for 1 h. After completion of the reaction it was quenched with saturated cool
aqueous Na2S2O3 (10 mL) and was extracted with ethyl acetate (3 x 10 mL). The organic phase
was collected and washed with water (3 x 5 mL), then dried with anhydrous Na2SO4, filtered
and evaporated in vacuo. The crude product was purified by silica gel column chromatography
(SiO2, 40-50% EtOAc/n-Hexane as eluent) to afford bis-indole-1,4-disubstituted-1,2,3-triazoles
3.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl) 3a: 98%
o
yield (0.1365 g) as a pink solid; m.p. 182-183 C; Rf = 0.13 (40% EtOAc/n-Hexane); IR
1
(KBr): 3135, 3052, 2922, 2851, 1634, 1489, 1466, 1332, 804, 736 cm-1; H NMR (400 MHz,
CDCl3) δ 7.36-7.25 (m, 10H), 7.20-7.12 (m, 10H), 7.07 (s, 2H), 6.94 (t, J = 7.6 Hz, 2H), 6.59
13
(s, 2H), 5.79 (s, 1H), 5.40 (s, 4H), 5.29 (s, 4H); C{1H} NMR (100 MHz, CDCl3) δ 145.0,
142.2, 136.5, 134.4, 131.7, 129.8, 128.9, 128.6, 128.3, 127.8, 127.4, 127.1, 121.8, 121.5, 119.8,
119.1, 118.4, 109.6, 53.9, 41.8, 39.4; HRMS (ESI) m/z C43H35ClN8 (M+H)+ calcd 699.2751,
found 699.2752.
3,3'-(phenylmethylene)-bis-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl) 3b3: CAS Number
1174761-01-3; 92% yield (0.1220 g) as a pink solid; m.p. 94-96 oC; Rf = 0.48 (50% EtOAc/n-
Hexane); IR (KBr): 3135, 3054, 2923, 2851, 1611, 1480, 1466, 1332, 736 cm-1; 1H NMR (400
MHz, CDCl3) δ 7.34-7.29 (m, 12H), 7.23-7.12 (m, 9H), 7.05 (s, 2H), 6.92 (t, J = 7.6 Hz, 2H),
13
6.59 (s, 2H), 5.82 (s, 1H), 5.40 (s, 4H), 5.30 (s, 2H), 5.29 (s, 4H); C{1H} NMR (100 MHz,
CDCl3) δ 145.1, 143.6, 136.5, 134.4, 128.9, 128.6, 128.5, 128.2, 127.8, 127.6, 127.1, 126.1,
121.7, 121.6, 119.9, 119.0, 118.9, 109.5, 53.9, 41.9, 40.0.
3,3'-(4-fluorophenylmethylene)-bis-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl) 3c: 97%
yield (0.1530 g) as a pink solid; m.p. 102-103 oC; Rf = 0.54 (50% EtOAc/n-Hexane); IR (KBr):
3135, 3052, 2922, 2851, 1634, 1506, 1466, 1332, 1221, 736 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.33-7.25 (m, 10H), 7.21-7.09 (m, 8H), 7.04 (s, 2H), 6.91 (t, J = 7.6 Hz, 2H), 6.88 (t, J = 8.8
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Hz, 2H), 6.55 (s, 2H), 5.77 (s, 1H), 5.38 (s, 4H), 5.27 (s, 2H), 5.26 (s, 2H); 13C{1H} NMR (100
MHz, CDCl3) δ 161.2 (d, J = 243.0 Hz), 144.9, 139.4 (d, J = 3.0 Hz), 136.5, 134.4, 129.8 (d, J
= 8.0 Hz), 128.9, 128.5, 127.7, 127.4, 127.0, 121.8, 121.5, 119.8, 119.0, 118.7, 114.8 (d, J =
21.0 Hz), 109.5, 53.9, 41.8, 39.2; HRMS (ESI) m/z C43H35FN8Na (M+Na)+ calcd 705.2866,
found 705.2870.
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3,3'-(4-methoxyphenylmethylene)-bis-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl)
3d3:
o
CAS Number 1174761-04-6; 78% yield 0.1240 g) as an orange solid; m.p. 153-155 C; Rf =
0.38 (50% EtOAc/n-Hexane); IR (KBr): 3137, 3052, 2923, 2851, 1610, 1509, 1465, 1331,
1265, 737 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.36-7.28 (m, 10H), 7.20-7.10 (m, 8H), 7.05 (s,
2H), 6.92 (t, J = 7.6 Hz, 2H), 6.77 (d, J = 8.8 Hz, 2H), 6.58 (s, 2H), 5.77 (s, 1H), 5.40 (s, 4H),
5.30 (s, 2H), 5.29 (s, 2H), 3.78 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 157.8, 145.2,
136.6, 135.8, 134.4, 129.4, 128.9, 128.6, 127.8, 127.4, 127.0, 121.7, 121.5, 120.0, 119.3, 118.9,
113.5, 109.5, 55.0, 53.9, 41.9, 39.1.
3,3'-(4-nitrophenylmethylene)-bis-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl) 3e: 17%
o
yield (0.0247 g) as a yellow solid; m.p. 181-182 C; Rf = 0.22 (50% EtOAc/n-Hexane); IR
(KBr): 3133, 3054, 2923, 2852, 1660, 1497, 1519, 1466, 1344, 743 cm-1; 1H NMR (400 MHz,
CDCl3) δ 8.08 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.4 Hz, 2H), 7.37-7.28 (m, 10H), 7.20-7.15 (m,
6H), 7.12 (s, 2H), 6.96 (t, J = 7.2 Hz, 2H), 6.63 (s, 2H), 5.92 (s, 1H), 5.42 (s, 4H), 5.30 (s, 4H);
13C{1H} NMR (100 MHz, CDCl3) δ 151.6, 146.5, 144.9, 136.6, 134.4, 129.3, 129.1, 128.8,
127.9, 127.3, 127.2, 123.6, 122.2, 121.6, 119.6, 119.4, 117.4, 109.7, 54.1, 42.0, 40.0; HRMS
(ESI) m/z C43H35N9O2Na (M+Na)+ calcd 732.2811, found 732.2808.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(4-nitrobenzyl)-1,2,3-triazol-4-yl)methyl)
3f: 81% yield (0.1278 g) as a red solid; m.p. 109-111 oC; Rf = 0.05 (40% EtOAc/n-Hexane); IR
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(KBr): 3127, 3042, 2922, 2851, 1609, 1489, 1522, 1466, 1347, 804, 734 cm-1; H NMR (400
MHz, CDCl3) δ 8.13 (d, J = 8.8 Hz, 4H), 7.33-7.26 (m, 8H), 7.23-7.10 (m, 8H), 6.93 (t, J = 7.6
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Hz, 2H), 6.65 (s, 2H), 5.79 (s, 1H), 5.48 (s, 4H), 5.30 (s, 4H); 13C{1H} NMR (100 MHz,
CDCl3) δ 147.9, 145.4, 142.2, 141.4, 136.5, 131.8, 129.8, 128.4, 128.3, 127.5, 127.1, 124.1,
122.0, 121.9, 119.9, 119.2, 118.6, 109.5, 52.9, 41.8, 39.4; HRMS (ESI) m/z C43H33ClN10O4Na
(M+Na)+ calcd 811.2272, found 811.2278.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(3-nitrobenzyl)-1,2,3-triazol-4-yl)methyl)
3g: 99% yield (0.1570 g) as a pink solid; m.p. 105-108 oC; Rf = 0.06 (40% EtOAc/n-Hexane);
IR (KBr): 3137, 3053, 2925, 2852, 1612, 1530, 1465, 1350, 806, 741 cm-1; 1H NMR (400
MHz, CDCl3) δ 8.22-8.16 (m, 2H), 8.05 (s, 2H), 7.57-7.50 (m, 4H), 7.32 (t, J = 7.6 Hz, 4H),
7.23-7.12 (m, 8H), 6.95 (t, J = 7.2 Hz, 2H), 6.63 (s, 2H), 5.80 (s, 1H), 5.53 (s, 4H), 5.32 (brs,
4H); 13C{1H} NMR (100 MHz, CDCl3) δ 148.3, 145.4, 142.2, 136.5, 133.8, 131.7, 130.1,
129.8, 128.3, 127.4, 127.1, 123.6, 122.6, 121.9, 119.8, 119.2, 118.6, 109.5, 52.8, 41.7, 39.4;
HRMS (ESI) m/z C43H33ClN10O4Na (M+Na)+ calcd 811.2272, found 811.2282.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(3-methoxybenzyl)-1,2,3-triazol-4-
yl)methyl) 3h: 98% yield (0.1485 g) as a pink solid; m.p. 98-100 oC; Rf = 0.14 (50% EtOAc/n-
Hexane); IR (KBr): 3135, 3052, 2923, 2851, 1602, 1490, 1465, 1332, 1264, 777, 742 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.25 (t, J = 8.0
Hz, 2H), 7.20 (brs, 4H), 7.15 (t, J = 7.6 Hz, 2H), 7.11 (s, 2H), 6.95 (t, J = 7.6 Hz, 2H), 6.87
(dd, J = 8.4, 1.6 Hz, 2H), 6.76 (t, J = 7.6 Hz, 2H), 6.70 (brs, 2H), 6.62 (s, 2H), 5.81 (s, 1H),
5.36 (s, 4H), 5.29 (s, 4H), 3.73 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 160.0, 145.0,
142.2, 136.5, 135.8, 131.7, 130.1, 129.8, 128.3, 127.5, 127.1, 121.9, 121.6, 120.0, 119.8, 119.1,
118.4, 114.0, 113.4, 109.6, 55.2, 53.9, 41.9, 39.4; HRMS (ESI) m/z C45H39ClN8O2Na (M+Na)+
calcd 781.2782, found 781.2777.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(2,3-dimethoxybenzyl)-1,2,3-triazol-4-
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yl)methyl) 3i: 99% yield (0.1692 g) as a pink solid; m.p. 94-95 C; Rf = 0.17 (50% EtOAc/n-
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Hexane); IR (KBr): 3139, 3053, 2923, 2851, 1613, 1505, 1465, 1331, 1228, 808, 742 cm-1; H
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NMR (400 MHz, CDCl3) δ 7.33 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.20 (s, 4H),
7.17-7.11 (m, 4H), 6.94 (t, J = 7.6 Hz, 2H), 6.83 (dd, J = 8.8, 2.0 Hz, 2H), 6.78 (d, J = 8.8 Hz,
2H), 6.66 (brs, 2H), 6.61 (s, 2H), 5.80 (s, 1H), 5.39 (s, 4H), 5.29 (s, 4H), 3.67 (s, 6H), 3.64 (s,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 153.6, 151.1, 144.5, 142.4, 136.6, 131.7, 129.9,
128.3, 127.5, 127.2, 123.6, 122.0, 121.8, 119.8, 119.1, 118.3, 115.8, 114.7, 111.7, 109.7, 55.7,
55.6, 49.1, 42.0, 39.5; HRMS (ESI) m/z C47H43ClN8O4Na (M+Na)+ calcd 841.2993, found
841.2997.
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triazol-4-yl)methyl) 3j: 84 % yield (0.1627 g) as a red solid; m.p. 94-95 C; Rf = 0.15 (40%
EtOAc/n-Hexane); IR (KBr): 3139, 3053, 2923, 2851, 1633, 1515, 1466, 1332, 1265, 784, 737
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.45-7.27 (m, 14H), 7.20 (s, 4H), 7.14 (t, J = 7.6 Hz, 2H),
7.08 (s, 2H), 6.94 (t, J = 7.2 Hz, 2H), 6.82 (d, J = 8.0 Hz, 2H), 6.74-6.67 (m, 4H), 6.60 (s, 2H),
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5.79 (s, 1H), 5.31 (s, 4H), 5.28 (s, 4H), 5.13 (s, 4H), 3.76 (s, 6H); C{1H} NMR (100 MHz,
CDCl3) δ 150.0, 148.5, 145.0, 142.3, 136.7, 136.6, 131.8, 129.9, 128.5, 128.3, 127.9, 127.5,
127.3, 127.2, 121.9, 121.4, 120.5, 119.9, 119.1, 118.4, 113.9, 111.5, 109.6, 71.0, 56.0, 53.9,
42.0, 39.5; HRMS (ESI) m/z C59H51ClN8O4Na (M+Na)+ calcd 993.3619, found 993.3629.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-phenylethyl-1,2,3-triazol-4-yl)methyl) 3k:
98 % yield (0.1489 g) as a pink solid; m.p. 83-85 oC; Rf = 0.16 (40% EtOAc/n-Hexane); IR
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(KBr): 3136, 3057, 2924, 2853, 1612, 1488, 1465, 1333, 804, 742 cm-1; H NMR (400 MHz,
CDCl3) δ 7.31 (t, J = 8.8 Hz, 4H), 7.24 (s, 4H), 7.20-7.12 (m, 8H), 7.02-6.94 (m, 6H), 6.85 (s,
2H), 6.60 (s, 2H), 5.82 (s, 1H), 5.27 (brs, 4H), 4.45 (t, J = 7.0 Hz, 4H), 3.09 (t, J = 7.2 Hz, 4H);
13C{1H} NMR (100 MHz, CDCl3) δ 144.3, 142.3, 136.8, 136.6, 131.8, 129.9, 128.7, 128.5,
128.4, 127.6, 127.2, 127.0, 121.9, 119.9, 119.2, 118.4, 109.6, 51.6, 42.0, 39.5, 36.6; HRMS
(ESI) m/z C45H39ClN8Na (M+Na)+ calcd 749.2884, found 749.2887.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-phenoxyethyl-1,2,3-triazol-4-yl)methyl) 3l:
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83 % yield (0.1252 g) as a pink solid; m.p. 92-94 C; Rf = 0.17 (50% EtOAc/n-Hexane); IR
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(KBr): 3140, 3052, 2923, 2851, 1599, 1489, 1466, 1333, 1242, 790, 740 cm-1; H NMR (400
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MHz, CDCl3) δ 7.37-7.29 (m, 6H), 7.27-7.13 (m, 10H), 7.00 (t, J = 7.6 Hz, 2H), 6.96 (t, J = 7.2
Hz, 2H), 6.72 (d, J = 8.4 Hz, 4H), 6.64 (s, 2H), 5.83 (s, 1H), 5.31 (s, 4H), 4.62 (t, J = 4.8 Hz,
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4H), 4.26 (t, J = 4.8 Hz, 4H); C{1H} NMR (100 MHz, CDCl3) δ 157.6, 144.6, 142.3, 136.6,
131.7, 129.9, 129.5, 128.3, 127.5, 127.2, 122.8, 121.9, 121.6, 119.9, 119.1, 118.5, 114.5, 109.6,
66.0, 49.6, 41.9, 39.4; HRMS (ESI) m/z C45H39ClN8O2Na (M+Na)+ calcd 781.2782, found
781.2779.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-naphthyloxyethyl-1,2,3-triazol-4-yl)methyl)
3m: 45 % yield (0.0767 g) as a red solid; m.p. 106-108 oC; Rf = 0.04 (50% EtOAc/n-Hexane);
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IR (KBr): 3133, 3053, 2923, 2851, 1632, 1581, 1464, 1333, 1269, 794, 740 cm-1; H NMR
(400 MHz, CDCl3) δ 7.91 (d, J = 8.4 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.48-7.42 (m, 4H),
7.37-7.27 (m, 10H), 7.16-7.07 (m, 6H), 6.96 (t, J = 7.6 Hz, 2H), 6.69 (d, J = 7.6 Hz, 2H), 6.61
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(s, 2H), 5.74 (s, 1H), 5.28 (s, 4H), 4.71 (t, J = 4.8 Hz, 4H), 4.39 (t, J = 4.8 Hz, 4H); C{1H}
NMR (100 MHz, CDCl3) δ 153.3, 144.9, 142.2, 136.6, 134.4, 131.7, 129.9, 128.3, 127.6,
127.5, 127.2, 126.6, 125.6, 125.6, 125.2, 122.6, 122.0, 121.3, 121.2, 120.0, 119.2, 118.5, 109.5,
105.0, 66.3, 49.7, 41.9, 39.4; HRMS (ESI) m/z C53H43ClN8O2Na (M+Na)+ calcd 881.3095,
found 881.3087.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(4-methoxybenzyldiacetyl)-1,2,3-triazol
o
-4-yl)methyl) 3n: 78 % yield (0.1352 g) as a pink solid; m.p. 78-79 C; Rf = 0.10 (50%
EtOAc/n-Hexane); IR (KBr): 3140, 3052, 2934, 2838, 1751, 1614, 1516, 1465, 1333, 1249,
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804, 742 cm-1; H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 7.2 Hz, 2H), 7.33 (d, J = 7.6 Hz,
2H), 7.24-7.22 (m, 8H), 7.19 (s, 2H), 7.16 (t, J = 7.5 Hz, 2H), 6.98 (t, J = 7.6 Hz, 2H), 6.86 (d,
J = 8.4 Hz, 4H), 6.64 (s, 2H), 5.83 (s, 1H), 5.34 (s, 2H), 5.33 (s, 2H), 5.10 (s, 4H), 5.02 (s, 4H),
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3.79 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 166.0, 159.9, 145.0, 142.3, 136.5, 131.7,
130.3, 129.8, 128.3, 127.4, 127.1, 126.5, 123.0, 121.9, 119.8, 119.1, 118.6, 114.0, 109.5, 67.7,
55.1, 50.6, 41.7, 39.3; HRMS (ESI) m/z C49H43ClN8O6Na (M+Na)+ calcd 897.2892, found
897.2899.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(2,3-dimethoxybenzyldiacetyl)-1,2,3-
triazol-4-yl)methyl) 3o: 77 % yield (0.1434 g) as a pink solid; m.p. 95-96 oC; Rf = 0.07 (50%
EtOAc/n-Hexane); IR (KBr): 3143, 3053, 2922, 2851, 1754, 1633, 1505, 1466, 1333, 1223,
805, 738 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.4 Hz, 4H), 7.26-7.22 (m, 6H), 7.16
(t, J = 7.2 Hz, 2H), 6.98 (t, J = 7.6 Hz, 2H), 6.86-6.79 (m, 6H), 6.65 (s, 2H), 5.83 (s, 1H), 5.35
(s, 2H), 5.34 (s, 2H), 5.20 (s, 4H), 5.06 (s, 4H), 3.76 (s, 6H), 3.74 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 166.1, 153.4, 151.8, 145.3, 142.2, 136.6, 131.8, 130.0, 128.4, 127.6, 127.2,
123.6, 123.1, 122.0, 119.9, 119.2, 118.8, 116.2, 114.5, 111.6, 109.6, 63.5, 56.0, 55.7, 50.8,
41.9, 39.4; HRMS (ESI) m/z C51H47ClN8O8Na (M+Na)+ calcd 957.3103, found 957.3101.
b
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-( -tetraacetylglucose)-1,2,3-triazol-4-yl)
methyl) 3p: 99 % yield (0.2326 g) as a red solid; m.p. 122-124 oC; Rf = 0.10 (50% EtOAc/n-
Hexane); IR (KBr): 3138, 3054, 2926, 2853, 1755, 1613, 1489, 1466, 1368, 1224, 805, 742
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.42 (s, 1H), 7.40 (s, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.33
(d, J = 7.6 Hz, 2H), 7.31-7.22 (m, 4H), 7.20 (t, J = 7.2 Hz, 2H), 7.03 (t, J = 7.6 Hz, 1H), 7.02
(t, J = 7.2 Hz, 1H), 6.71 (s, 1H), 6.68 (s, 1H), 5.85 (s, 1H), 5.79 (d, J = 8.8 Hz, 2H), 5.40-5.30
(m, 8H), 5.21 (t, J = 9.6 Hz, 2H), 4.27 (ddd, J = 12.8, 8.4, 5.2 Hz, 2H), 4.11 (brd, J = 12.4 Hz,
2H), 3.96 (brdd, J = 10.0, 3.6 Hz, 2H), 2.05 (s, 6H), 2.04 (s, 6H), 2.02 (s, 3H), 2.00 (s, 3H),
1.72 (s, 3H), 1.68 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 170.4, 169.9, 169.3, 168.7,
168.7, 145.5, 145.4, 142.3, 136.6, 136.6, 131.8, 130.0, 128.4, 127.7, 127.6, 127.3, 122.0, 120.3,
120.2, 120.0, 119.99, 119.3, 119.28, 118.7, 118.66, 109.6, 109.56, 85.6, 85.57, 75.2, 75.1, 72.6,
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70.1, 70.0, 67.7, 67.6, 61.5, 61.47, 41.9, 41.8, 39.5, 20.6, 20.5, 19.9, 19.8; HRMS (ESI) m/z
C57H59ClN8O18Na (M+Na)+ calcd 1201.3534, found 1201.3534.
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yield (0.1183 g) as a red oil; Rf = 0.36 (40% EtOAc/n-Hexane); IR (KBr): 3133, 3053, 2925,
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2854, 1633, 1488, 1466, 1332, 804, 740 cm-1; H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.4
Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.25-7.22 (m, 4H), 7.18 (t, J = 7.6 Hz, 2H), 7.10 (s, 2H),
7.00 (t, J = 7.6 Hz, 2H), 6.65 (s, 2H), 5.84 (s, 1H), 5.33 (s, 4H), 4.22 (t, J = 7.2 Hz, 4H), 1.84-
1.79 (m, 4H), 1.27-1.24 (m, 20H), 0.87 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ
144.4, 142.2, 136.5, 131.6, 129.8, 128.2, 127.4, 127.1, 121.8, 121.3, 119.7, 119.0, 118.3, 109.5,
50.2, 41.9, 39.4, 31.5, 30.0, 28.8, 28.7, 26.2, 22.4, 13.9; HRMS (ESI) m/z C45H55ClN8Na
(M+Na)+ calcd 765.4136, found 765.4135.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-dodecyl-1,2,3-triazol-4-yl)methyl) 3r: 90 %
yield (0.1532 g) as a brown oil; Rf = 0.35 (30% EtOAc/n-Hexane); IR (KBr): 3133, 3055,
2925, 2854, 1614, 1489, 1466, 1333, 803, 741 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J =
8.4 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.26 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 8.8 Hz, 2H), 7.18
(t, J = 7.6 Hz, 2H), 7.09 (s, 2H), 7.00 (t, J = 7.2 Hz, 2H), 6.64 (s, 2H), 5.84 (s, 1H), 5.33 (s,
4H), 4.22 (t, J = 7.2 Hz, 4H), 1.80 (quin, J = 7.6 Hz, 4H), 1.24 (brs, 36H), 0.88 (t, J = 6.8 Hz,
6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.5, 142.3, 136.6, 131.8, 129.9, 128.3, 127.5,
127.2, 121.9, 121.3, 119.8, 119.1, 118.4, 109.6, 50.3, 42.0, 39.5, 31.8, 30.1, 29.5, 29.4, 29.3,
29.2, 28.9, 26.4, 14.0; HRMS (ESI) m/z C53H71ClN8Na (M+Na)+ calcd 877.5388, found
877.5384.
General procedure for one-pot four-step bis-indole triazoles derivatives: The first step, a
stirred solution of indole 1(1.1 mmol) in CH3CN (1 mL) was mixed with aldehyde 2(0.5
mmol), I2 powder (9.5 mg, 0.075 mmol) and H2SO4-SiO2 (20 mg) at room temperature. TLC
showed the conversion was complete. In the second step KOH (266.5 mg, 4.75 mmol) and
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propargyl bromide (0.1 mL, 1.5 mmol) was added at room temperature and the stirring was
continued for 1 h. The reaction mixture was filtered to remove salt and the solvent of the
filtrate was evaporated to dryness. The reaction mixture was re-dissolved in DMF (0.50 mL). A
solution of NaN3 (97.5 mg, 1.5 mmol) and alkyl halide 3 (1.5 mmol) in DMF (0.5 mL) was
added while stirring at room temperature. Finally, CuI (33.3 mg, 0.175 mmol), Et3N (0.2 mL,
1.5 mmol), and solution of alkyl azide was added and stirring was continued at room
temperature for 1 h. After completion of the reaction, it was quenched with saturated cool
aqueous Na2S2O3 and extracted with ethyl acetate (3x10 mL). The organic phase was collected
and washed with water (3x5 mL), then dried with anhydrous Na2SO4, filtered and evaporated
in vacuo. The crude product was purified by silica gel column chromatography (SiO2, 40-50%
EtOAc/Hexane as eluent) to afford bis-indole-1,4-disubstituted-1,2,3-triazoles 4.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-methyl-1,2,3-triazol-4-yl)methyl) 4d: 90 %
yield (0.1999 g) as a brown solid; m.p. 97-99 oC; Rf = 0.03 (50% EtOAc/n-Hexane); IR (KBr):
3138, 3052, 2922, 2851, 1633, 1488, 1466, 1333, 804, 739 cm-1; 1H NMR (400 MHz, CDCl3) δ
7.34 (t, J = 7.6 Hz, 4H), 7.25-7.21 (m, 4H), 7.18 (t, J = 7.6 Hz, 2H), 7.10 (s, 2H), 7.00 (t, J =
7.6 Hz, 2H), 6.64 (s, 2H), 5.83 (s, 1H), 5.32 (s, 2H), 5.31 (s, 2H), 3.97 (s, 6H); 13C{1H} NMR
(100 MHz, CDCl3) δ 144.7, 142.2, 136.5, 131.7, 129.8, 128.3, 127.4, 127.1, 122.5, 121.8,
119.8, 119.1, 118.4, 109.5, 41.8, 39.4, 36.5; HRMS (ESI) m/z C31H27ClN8Na (M+Na)+ calcd
569.1945, found 569.1942.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(4-nitroxybenzyldiacetyl)-1,2,3-triazol
o
-4-yl)methyl) 4e: 59 % yield (0.2651 g) as a red solid; m.p. 98-100 C; Rf = 0.10 (50%
EtOAc/n-Hexane); IR (KBr): 3144, 3055, 2922, 2851, 1759, 1608, 1522, 1489, 1466, 1347,
1195, 805, 738 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.16 (d, J = 8.4 Hz, 4H), 7.42 (d, J = 8.4
Hz, 4H), 7.34 (d, J = 7.6 Hz, 2H), 7.32 (d, J = 7.6 Hz, 2H), 7.25-7.20 (m, 6H), 7.14 (t, J = 7.2
Hz, 2H), 6.97 (t, J = 7.6 Hz, 2H), 6.44 (s, 2H), 5.83 (s, 1H), 5.34 (s, 2H), 5.33 (s, 2H), 5.25 (s,
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4H), 5.12 (s, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.8, 147.6, 145.0, 142.3, 141.4,
136.4, 131.6, 129.8, 128.4, 128.2, 127.4, 127.0, 123.7, 123.1, 121.8, 119.8, 119.1, 118.5, 109.5,
66.0, 50.4, 41.6, 39.2; HRMS (ESI) m/z C47H37ClN10O8Na (M+Na)+ calcd 927.2382, found
927.2379.
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3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(menthyldiacetyl)-1,2,3-triazol-4-yl)methyl)
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4f: 84 % yield (0.3846 g) as a red solid; m.p. 112-113 C; Rf = 0.15 (30% EtOAc/n-Hexane);
IR (KBr): 3139, 3054, 2956, 2870, 1746, 1613, 1489, 1465, 1334, 1220, 803, 740 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.27-7.22 (m,
6H), 7.18 (t, J = 7.6 Hz, 2H), 6.99 (t, J = 7.6 Hz, 2H), 6.65 (s, 2H), 5.83 (s, 1H), 5.36 (s, 4H),
5.02 (t, J = 4.5 Hz, 4H), 4.74 (td, J = 10.8, 4.4 Hz, 2H), 1.96 (brd, J = 12.0 Hz, 2H), 1.77-1.62
(m, 8H), 1.34 (brt, J = 12.0 Hz, 2H), 1.10-0.99 (m, 2H), 0.97 (d, J = 11.6 Hz, 6H), 0.86 (d, J =
6.8 Hz, 6H), 0.71 (d, J = 6.8 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 165.6, 145.0, 142.2,
136.5, 131.7, 129.9, 128.3, 127.5, 127.1, 123.0, 121.9, 119.8, 119.1, 118.5, 109.6, 76.8, 50.8,
46.6, 41.8, 40.5, 39.4, 33.8, 31.2, 26.1, 23.2, 21.8, 20.6, 16.2; HRMS (ESI) m/z
C53H63ClN8O4Na (M+Na)+ calcd 933.4558, found 933.4569.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-penthyl-1,2,3-triazol-4-yl)methyl) 4h: 19 %
o
yield (0.0635 g) as a red solid; m.p. 77-79 C; Rf = 0.10 (30% EtOAc/n-Hexane); IR (KBr):
3134, 3054, 2927, 2856, 1614, 1489, 1466, 1333, 804, 749 cm-1; 1H NMR (400 MHz, CDCl3) δ
7.35 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.24 (d, J = 4.0 Hz, 4H), 7.18 (t, J = 8.0 Hz,
2H), 7.10 (s, 2H), 7.00 (t, J = 7.6 Hz, 2H), 6.64 (s, 2H), 5.84 (s, 1H), 5.33 (brs, 4H), 4.22 (t, J =
7.2 Hz, 4H), 1.81 (quin, J = 7.6 Hz, 4H), 1.35-1.26 (m, 8H), 0.87 (t, J = 7.2 Hz, 6H); 13C{1H}
NMR (100 MHz, CDCl3) δ 144.6, 142.3, 136.6, 131.8, 129.9, 128.4, 127.5, 127.2, 121.1,
121.4, 119.9, 119.1, 118.5, 109.6, 50.3, 42.0, 39.5, 29.8, 28.4, 22.0, 13.8; HRMS (ESI) m/z
C39H43ClN8Na (M+Na)+ calcd 681.3197, found 681.3207.
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3,3'-(phenylmethylene)-bis-indole-((1-(3-methoxybenzyl)-1,2,3-triazol-4-yl)methyl) 4m: 88
% yield (0.3193 g) as a pink solid; m.p. 87-89 oC; Rf = 0.16 (40% EtOAc/n-Hexane); IR (KBr):
3138, 3054, 2923, 2851, 1602, 1492, 1466, 1323, 1265, 743 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.35-7.27 (m, 6H), 7.27-7.19 (m, 5H), 7.14 (t, J = 7.2 Hz, 2H), 7.08 (s, 2H), 6.93 (t, J = 7.6
Hz, 2H), 6.86 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 7.6 Hz, 2H), 6.69 (brs, 2H), 6.62 (s, 2H), 5.84 (s,
1H), 5.35 (s, 4H), 5.28 (s, 4H), 3.73 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 160.0, 145.2,
143.7, 136.6, 135.9, 130.1, 128.5, 128.2, 127.7, 127.2, 126.1, 121.8, 121.6, 120.0, 119.0, 114.1,
113.4, 109.5, 55.2, 53.9, 42.0, 40.0; HRMS (ESI) m/z C45H40N8O2Na (M+Na)+ calcd 747.3172,
found 747.3180.
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3,3'-(4-fluorophenylmethylene)-bis-indole-((1-(3-methoxybenzyl)-1,2,3-triazol-4-
yl)methyl) 4o: 80 % yield (0.2966 g) as a pink solid; m.p. 91-92 oC; Rf = 0.10 (50% EtOAc/n-
Hexane); IR (KBr): 3136, 3052, 2922, 2851, 1602, 1506, 1466, 1332, 1265, 1221, 740 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.4 Hz, 2H), 7.29 (d, J = 8.4 Hz, 2H), 7.27-7.19 (m,
4H), 7.14 (t, J = 7.6 Hz, 2H), 7.08 (s, 2H), 6.94 (t, J = 8.0 Hz, 2H), 6.91 (t, J = 8.8 Hz, 2H),
6.86 (dd, J = 8.0, 2.0 Hz, 2H), 6.75 (d, J = 7.6 Hz, 2H), 6.69 (brs, 2H), 6.59 (s, 2H), 5.80 (s,
1H), 5.37 (s, 4H), 5.29 (s, 4H), 3.73 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 161.1 (d, J =
243.0 Hz), 159.8, 144.9, 139.3 (d, J = 3.0 Hz), 136.5, 135.8, 129.9, 129.8 (d, J = 8.0 Hz),
127.4, 127.0, 121.7, 121.6, 119.8, 119.77, 119.0, 118.7, 114.8 (d, J = 21.0 Hz), 113.9, 113.4,
109.5, 55.0, 53.7, 41.7, 39.2; HRMS (ESI) m/z C45H39FN8O2Na (M+Na)+ calcd 765.3078,
found 765.3075.
3,3'-(4-methoxyphenylmethylene)-bis-indole-((1-(3-methoxybenzyl)-1,2,3-triazol-4-
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yl)methyl) 4p: 63 % yield (0.2376 g) as an orange solid; m.p. 89-91 C; Rf = 0.16 (50%
EtOAc/n-Hexane); IR (KBr): 3137, 3053, 2923, 2851, 1603, 1509, 1466, 1332, 1264, 739 cm-
1; 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 8.0 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.26-7.22
(m, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.13 (t, J = 8.0 Hz, 2H), 7.06 (s, 2H), 6.92 (t, J = 7.6 Hz,
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2H), 6.86 (dd, J =8.4, 2.0 Hz, 2H), 6.80-6.73 (m, 4H), 6.68 (brs, 2H), 6.59 (s, 2H), 5.77 (s,
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1H), 5.37 (s, 4H), 5.30 (s, 2H), 5.29 (s, 4H), 3.78 (s, 3H), 3.72 (s, 6H); C{1H} NMR (100
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MHz, CDCl3) δ 160.0, 157.9, 145.2, 136.6, 135.9, 135.8, 130.1, 129.4, 127.7, 127.1, 121.7,
121.6, 120.0, 119.95, 119.4, 119.0, 114.1, 113.6, 113.4, 109.5, 55.2, 55.1, 53.9, 42.0, 39.2;
HRMS (ESI) m/z C46H42N8O3Na (M+Na)+ calcd 777.3278, found 777.3272.
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3,3'-(phenylmethylene)-bis-indole-((1-(4-fluorobenzyl)-1,2,3-triazol-4-yl)methyl) 4q:
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86 % yield (0.3019 g) as a pink solid; m.p. 103-104 C; Rf = 0.16 (40% EtOAc/n-Hexane); IR
(KBr): 3134, 3054, 2923, 2851, 1608, 1509, 1465, 1332, 1225, 741 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.34-7.12 (m, 15H), 7.04 (s, 2H), 7.02 (t, J = 8.4 Hz, 4H), 6.93 (t, J = 7.2 Hz, 2H),
6.60 (s, 2H), 5.82 (s, 1H), 5.37 (s, 4H), 5.30 (s, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.8
(d, J = 246.0 Hz), 145.4, 143. 7, 136.6, 130.2 (d, J = 3.0 Hz), 129.8 (d, J = 8.0 Hz), 128.5,
128.2, 127.7, 127.2, 126.2, 121.8, 121.5, 120.0, 119.1, 119.06, 116.4 (d, J = 21.0 Hz), 109.5,
53.3, 42.0, 40.0; HRMS (ESI) m/z C43H34F2N8Na (M+Na)+ calcd 723.2772, found 723.2779.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-(4-fluorobenzyl)-1,2,3-triazol-4-yl)methyl)
4r: 85 % yield (0.3109 g) as a pink solid; m.p. 96-98 oC; Rf = 0.10 (40% EtOAc/n-Hexane); IR
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(KBr): 3127, 3054, 2921, 2850, 1644, 1510, 1466, 1332, 1224, 785, 742 cm-1; H NMR (400
MHz, CDCl3) δ 7.31 (t, J = 8.0 Hz, 4H), 7.21-7.13 (m, 10H), 7.08 (s, 2H), 7.02 (t, J = 8.8 Hz,
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4H), 6.95 (t, J = 7.6 Hz, 2H), 6.60 (s, 2H), 5.79 (s, 1H), 5.37 (s, 4H), 5.30 (brs, 4H); C{1H}
NMR (100 MHz, CDCl3) δ 162.8 (d, J = 247.0 Hz), 145.2, 142.3, 136.6, 131.8, 130.3 (d, J =
3.0 Hz), 129.9, 129.8 (d, J = 8.0 Hz), 128.4, 127.5, 127.1, 121.9, 121.5, 119.9, 119.2, 118.5,
116.0 (d, J = 22.0 Hz), 109.6, 53.3, 41.9, 39.5; HRMS (ESI) m/z C43H33ClF2N8Na (M+Na)+
calcd 757.2382, found 757.2395.
3,3'-(4-methoxyphenylmethylene)-bis-indole-((1-(4-fluorobenzyl)-1,2,3-triazol-4-
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yl)methyl) 4s: 82 % yield (0.3480 g) as an orange solid; m.p. 96-97 C; Rf = 0.18 (50%
EtOAc/n-Hexane); IR (KBr): 3133, 3052, 2927, 2852, 1609, 1509, 1465, 1332, 1247, 1225,
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742 cm-1; H NMR (400 MHz, CDCl3) δ 7.32 (t, J = 8.5 Hz, 4H), 7.20-7.11 (m, 8H), 7.05 (s,
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2H), 7.02 (t, J = 8.4 Hz, 4H), 6.93 (t, J = 7.2 Hz, 2H), 6.78 (d, J = 8.4 Hz, 2H), 6.60 (s, 2H),
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162.8 (d, J = 247.0 Hz), 157.9, 145.4, 136.6, 135.8, 130.3 (d, J = 3.0 Hz), 129.8 (d, J = 8.0
Hz), 129.4, 127.7, 127.1, 121.8, 121.5, 120.0, 119.4, 119.0, 116.0 (d, J = 22.0 Hz), 113.6,
109.5, 55.1, 53.3, 42.0, 39.2; HRMS (ESI) m/z C44H36F2N8O Na (M+Na)+ calcd 753.2878,
found 753.2881.
3,3'-(4-chlorophenylmethylene)-bis-indole-((1-buthyl-1,2,3-triazol-4-yl)methyl) 4t: 85 %
yield (0.2933 g) as a brown solid; m.p. 82-83 oC; Rf = 0.14 (40% EtOAc/n-Hexane); IR (KBr):
3135, 3051, 2924, 2852, 1633, 1489, 1466, 1332, 804, 740 cm-1; 1H NMR (400 MHz, CDCl3) δ
7.35 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.6 Hz, 2H), 7.25 (d, J = 8.8 Hz, 2H), 7.23 (d, J = 8.8 Hz,
2H), 7.18 (t, J = 7.6 Hz, 2H), 7.09 (s, 2H), 7.00 (t, J = 7.6 Hz, 2H), 6.64 (s, 2H), 5.84 (s, 1H),
5.33 (brs, 4H), 4.23 (t, J = 7.2 Hz, 4H), 1.79 (quin, J = 7.6 Hz, 4H), 1.29 (sex, J = 7.6 Hz, 4H),
0.92 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.4, 142.2, 136.5, 131.6, 129.8,
128.2, 127.4, 127.1, 121.8, 121.3, 119.7, 119.0, 118.3, 109.5, 49.8, 41.8, 39.4, 31.9, 19.4, 13.2;
HRMS (ESI) m/z C37H39ClN8Na (M+Na)+ calcd 653.2884, found 653.2887.
3,3'-(4-fluorophenylmethylene)-bis-indole-((1-buthyl-1,2,3-triazol-4-yl)methyl) 4u: 82 %
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yield (0.2656 g) as a pink solid; m.p. 82-83 C; Rf = 0.18 (40% EtOAc/n-Hexane); IR (KBr):
3135, 3051, 2924, 2851, 1633, 1506, 1466, 1332, 1220, 739 cm-1; 1H NMR (400 MHz, CDCl3)
δ 7.35 (d, J = 8.4 Hz, 4H), 7.29-7.26 (m, 2H), 7.18 (t, J = 7.6 Hz, 2H), 7.09 (s, 2H), 7.00 (t, J =
7.6 Hz, 2H), 6.95 (t, J = 8.4 Hz, 2H), 6.63 (s, 2H), 5.85 (s, 1H), 5.33 (s, 4H), 4.23 (t, J = 7.2
Hz, 4H), 1.79 (quin, J = 7.6 Hz, 4H), 1.29 (sex, J = 7.2 Hz, 4H), 0.92 (t, J = 7.6 Hz, 6H);
13C{1H} NMR (100 MHz, CDCl3) δ 161.2 (d, J = 242.0 Hz), 144.4, 139.4 (d, J = 3.0 Hz),
136.6, 129.8 (d, J = 8.0 Hz), 127.5, 127.1, 121.8, 121.3, 119.8, 119.0, 118.7, 114.8 (d, J = 21.0
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Hz), 109.5, 49.9, 41.8, 39.2, 32.0, 19.5, 13.2; HRMS (ESI) m/z C37H39FN8Na (M+Na)+ calcd
637.3179, found 637.3179.
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% yield (0.1278 g) as an orange solid; m.p. 80-81 C; Rf = 0.20 (50% EtOAc/n-Hexane); IR
(KBr): 3134, 3053, 2926, 2853, 1610, 1509, 1465, 1332, 1247, 741 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.37 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.16 (t, J
= 7.2 Hz, 2H), 7.06 (s, 2H), 6.98 (t, J = 7.6 Hz, 2H), 6.81 (d, J = 8.4 Hz, 2H), 6.64 (s, 2H), 5.82
(s, 1H), 5.33 (brs, 2H), 5.32 (brs, 2H), 4.22 (t, J = 7.6 Hz, 4H), 3.78 (s, 3H), 1.78 (quin, J = 7.6
Hz, 4H), 1.28 (sex, J = 7.6 Hz, 4H), 0.91 (t, J = 7.6 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3)
δ 157.9, 144.8, 136.7, 135.9, 129.5, 127.7, 127.2, 121.8, 121.3, 120.1, 119.4, 119.0, 113.6,
109.5, 55.2, 50.1, 42.1, 39.2, 32.1, 19.6, 13.4; HRMS (ESI) m/z C38H42N8ONa (M+Na)+ calcd
649.3379, found 649.3383.
3,3'-(phenylmethylene)-bis-indole-((1-octhyl-1,2,3-triazol-4-yl)methyl) 4w: 76 % yield
(0.2695 g) as a red oil; Rf = 0.27 (40% EtOAc/n-Hexane); IR (KBr): 3133, 3056, 2927, 2856,
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1613, 1493, 1466, 1333, 741 cm-1; H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 7.6 Hz, 2H),
7.33 (d, J = 8.0 Hz, 4H), 7.29-7.21 (m, 3H), 7.16 (t, J = 7.6 Hz, 2H), 7.06 (s, 2H), 6.98 (t, J =
7.2 Hz, 2H), 6.65 (s, 2H), 5.87 (s, 1H), 5.33 (s, 4H), 4.21 (t, J = 7.2 Hz, 4H), 1.83-1.78 (m,
4H), 1.26-1.24 (m, 20H), 0.87 (t, J = 7.2 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.6,
143.6, 136.5, 128.5, 128.1, 127.6, 127.2, 126.1, 121.7, 121.3, 119.9, 118.9, 109.5, 50.2, 41.9,
40.0, 31.5, 30.0, 28.8, 28.7, 26.2, 22.4, 13.9; HRMS (ESI) m/z C45H56N8Na (M+Na)+ calcd
731.4526, found 731.4518.
3,3'-(4-fluorophenylmethylene)-bis-indole-((1-octhyl-1,2,3-triazol-4-yl)methyl) 4y: 81 %
yield (0.2372 g) as a red oil; Rf = 0.34 (40% EtOAc/n-Hexane); IR (KBr): 3133, 3054, 2927,
2856, 1602, 1506, 1466, 1333, 1221, 741 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.34 (d, J = 8.4
Hz, 4H), 7.29-7.27 (m, 2H), 7.17 (t, J = 7.2 Hz, 2H), 7.09 (s, 2H), 7.00 (t, J = 7.2 Hz, 2H), 6.95
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(t, J = 8.4 Hz, 2H), 6.64 (s, 2H), 5.85 (s, 1H), 5.33 (brs, 4H), 4.21 (t, J = 7.2 Hz, 4H), 1.84-1.78
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(m, 4H), 1.26-1.24 (m, 20H), 0.87 (t, J = 7.2 Hz, 6H); C{1H} NMR (100 MHz, CDCl3) δ
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161.3 (d, J = 243.0 Hz), 144.6, 139.4 (d, J = 3.0 Hz), 136.6, 129.9 (d, J = 8.0 Hz), 127.5,
127.2, 121.8, 121.4, 119.9, 119.0, 118.8, 114.9 (d, J = 21.0 Hz), 109.6, 50.3, 42.0, 39.3, 31.6,
30.1, 28.9, 28.8, 26.3, 22.5, 14.0; HRMS (ESI) m/z C45H55FN8Na (M+Na)+ calcd 749.4431,
found 749.4434.
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3,3'-(4-chlorophenylmethylene)-bis-5-fluoro-indole-((1-benzyl-1,2,3-triazol-4-yl)methyl)
4z: 97 % yield (0.1419 g) as a pink solid; m.p. 133-135 oC; Rf = 0.36 (40% EtOAc/n-Hexane);
IR (KBr): 3132, 3066, 2924, 2853, 1620, 1488, 1455, 1321, 1270, 796, 729 cm-1; 1H NMR
(400 MHz, CDCl3) δ 7.35-7.33 (m, 6H), 7.24-7.16 (m, 10H), 7.10 (s, 2H), 6.91-6.86 (m, 4H),
6.62 (s, 2H), 5.63 (s, 1H), 5.43 (s, 4H), 5.28 (s, 2H), 5.27 (s, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 157.5 (d, J = 233.0 Hz), 144.8, 141.5, 134.4, 133.3, 132.1, 129.8, 129.0, 128.7, 128.7,
128.6, 127.9, 127.7 (d, J = 9.0 Hz), 121.5, 118.0 (d, J = 5.0 Hz), 110.5 (d, J = 6.0 Hz), 110.4
(d, J = 23.0 Hz), 104.7 (d, J = 23.0 Hz), 54.1, 42.2, 39.5; HRMS (ESI) m/z C43H33ClF2N8Na
(M+Na)+ calcd 757.2382, found 757.2384.
3,3'-(4-chlorophenylmethylene)-bis-5-methoxy-indole-((1-benzyl-1,2,3-triazol-4-
o
yl)methyl) 4aa: 70 % yield (0.2667 g) as a pink solid; m.p. 133-135 C; Rf = 0.15 (40%
EtOAc/n-Hexane); IR (KBr): 3132, 3066, 2924, 2853, 1620, 1488, 1455, 1321, 1270, 796, 729
cm-1; 1H NMR (400 MHz, CDCl3) δ 7.34-7.31 (m, 6H), 7.22 (d, J = 8.8 Hz, 2H), 7.20-7.16 (m,
8H), 7.09 (s, 2H), 6.82 (dd, J = 8.8, 2.4 Hz, 2H), 6.72 (dd, J = 2.4 Hz, 2H), 6.72 (s, 1H), 6.58
(s, 2H), 5.68 (s, 1H), 5.41 (s, 4H), 5.25 (s, 2H), 5.24 (s, 2H), 3.65 (s, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 153.8, 145.2, 142.2, 134.5, 132.0, 131.8, 129.9, 129.0, 128.7, 128.4, 128.0,
127.9, 121.6, 117.8, 111.7, 110.4, 102.3, 55.9, 54.1, 42.2, 39.5; HRMS (ESI) m/z
C45H39ClN8O2Na (M+Na)+ calcd 781.2782, found 781.2788.
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3,3'-(4-chlorophenylmethylene)-bis-5-fluoro-indole-((1- octhyl -1,2,3-triazol-4-yl)methyl)
4bb: 65 % yield (0.1008 g) as a yellow oil; Rf = 0.45 (40% EtOAc/n-Hexane); IR (KBr): 3135,
3080, 2927, 2856, 1623, 1488, 1456, 1321, 1182, 795, 736 cm-1; 1H NMR (400 MHz, CDCl3) δ
7.29-7.22 (m, 6H), 7.11 (s, 2H), 6.92-6.88 (m, 4H), 6.67 (s, 2H), 5.67 (s, 1H), 5.34 (d, J = 16.0
Hz, 2H), 5.29 (d, J = 16.0 Hz, 2H), 4.24 (t, J = 7.2 Hz, 4H), 1.83-1.80 (m, 4H), 1.26-1.24 (m,
20H), 0.86 (t, J = 6.8 Hz, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 157.5 (d, J = 234.0 Hz),
144.3, 141.5, 133.3, 132.1, 129.8, 128.7, 128.5, 127.7 (d, J = 9.0 Hz), 121.3, 117.9 (d, J = 5.0
H), 110.5 (d, J = 9.0 Hz), 110.3 (d, J = 26.0 Hz), 104.7 (d, J = 24.0 Hz), 50.4, 42.3, 39.6, 31.6,
30.1, 28.9, 28.8, 26.3, 22.5, 14.0; HRMS (ESI) m/z C45H53ClF2N8Na (M+Na)+ calcd 801.3947,
found 801.3951.
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3,3'-(4-chlorophenylmethylene)-bis-5-methoxy-indole-((1- octhyl -1,2,3-triazol-4-yl)
methyl) 4cc: 84 % yield (0.1340 g) as a pink solid; m.p. 142-143 oC; Rf = 0.41 (40% EtOAc/n-
Hexane); IR (KBr): 3133, 3080, 2927, 2855, 1621, 1488, 1452, 1318, 1217, 798, 734 cm-1; 1H
NMR (400 MHz, CDCl3) δ 7.26-7.23 (m, 6H), 7.10 (s, 2H), 6.83 (dd, J = 8.8, 2.0 Hz, 2H), 6.75
(d, J = 1.6 Hz, 2H), 6.62 (s, 2H), 5.71 (s, 1H), 5.29 (brs, 4H), 4.22 (t, J = 7.6 Hz, 4H), 3.68 (s,
6H), 1.82-1.79 (m, 4H), 1.26-1.24 (m, 20H), 0.87 (t, J = 6.8 Hz, 6H); 13C{1H} NMR (100
MHz, CDCl3) δ 153.7, 144.6, 142.2, 132.0, 131.8, 129.9, 128.4, 128.0, 127.9, 121.3, 117.8,
111.6, 110.4, 102.3, 55.9, 50.3, 42.3, 39.6, 31.6, 30.2, 29.0, 28.8, 26.4, 22.5, 14.0; HRMS
(ESI) m/z C47H59ClN8O2Na (M+Na)+ calcd 825.4347, found 825.4341.
3,3'-(4-chlorophenylmethylene)-bis-5-(1-benzyl-1,2,3-triazol-4-yl-methyl)-indole-((1-
benzyl-1,2,3-triazol-4-yl)methyl) 5: According for general procedure of one-pot four-step, a
stirred solution of indole 1d (146.5 mg, 1.1 mmol) in CH3CN (1 mL) was mixed with aldehyde
2a( 70.0 mg, 0.5 mmol). In the second step KOH (266.5 mg, 4.75 mmol) and propargyl
bromide (0.2 mL, 2.5 mmol) was added at room temperature and the stirring was continued for
1 h, NaN3 (162.5 mg, 2.5 mmol), benzyl bromide (0.3 mL, 2.5 mmol), CuI (66.6 mg, 0.35
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mmol) and Et3N (0.4 mL, 2.5 mmol) in final step. The crude product was purified by silica gel
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column chromatography (SiO2, 40% EtOAc/n-Hexane as eluent) to give of product 5 as a
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brown solid (417.8 mg, 78%); m.p. 108-110 C; Rf = 0.24 (40% EtOAc/n-Hexane); IR (KBr):
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3137, 3064, 2924, 2853, 1619, 1487, 1456, 1329, 1195, 798, 729 cm-1; 1H NMR (400 MHz,
CDCl3) δ 7.41 (s, 2H), 7.33-7.30 (m, 12H), 7.24-7.19 (m, 6H), 7.17-7.13 (m, 10H), 6.83 (dd, J
= 8.8, 2.0 Hz, 2H), 6.80 (d, J = 2.0 Hz, 2H), 6.58 (s, 2H), 5.62 (s, 1H), 5.45 (s, 4H), 5.37 (s,
4H), 5.23 (s, 4H), 4.98 (s, 4H); 13C{1H} NMR (100 MHz, CDCl3) δ 152.4, 144.9, 144.8, 142.1,
134.6, 134.6, 132.3, 131.7, 129.9, 129.0, 128.98, 128.7, 128.6, 128.4, 128.0, 127.9, 122.5,
121.7, 117.8, 112.4, 110.4, 104.0, 63.0, 54.1, 54.0, 42.1, 39.6; HRMS (ESI) m/z
C63H53ClN14O2Na (M+Na)+ calcd 1095.4062, found 1095.4058.
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General procedure for one-pot four-step compound 7: The first step, a stirred solution of
indole 1a (117.2 mg, 1.0 mmol) in CH3CN (0.6 mL) was mixed with terephthalaldehyde 6
(26.8 mg, 0.2 mmol), I2 powder (10.2 mg, 0.08 mmol) and H2SO4-SiO2 (20 mg) at room
temperature. TLC showed the conversion was complete. In the second step KOH (238.4 mg,
4.25 mmol) and propargyl bromide (0.1 mL, 1.3 mmol) was added at room temperature and the
stirring was continued for 1 h. The reaction mixture was filtered to remove salt and the solvent
of the filtrate was evaporated to dryness. The reaction mixture was redissolved in DMF (0.50
mL). A solution of NaN3 (84.5 mg, 1.3 mmol) and benzyl bromide (0.2 mL, 1.3 mmol) in
DMF (0.5 mL) was added while stirring at room temperature. Finally, CuI (30.5 mg, 0.16
mmol), Et3N (0.2 mL, 1.3 mmol) and solution of benzyl azide was added and stirring was
continued at room temperature for 1 h. After completion of the reaction it was quenched with
saturated cool aqueous Na2S2O3 (10 mL) and extracted with dichloromethane (3 x 10 mL). The
organic phase was collected and washed with water (3 x 5 mL), then dried with anhydrous
Na2SO4, filtered and evaporated in vacuo. The crude product was purified by silica gel column
chromatography (SiO2, 70% EtOAc/n-Hexane as eluent) to afford product 7 as a pink solid
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(170.6 mg, 61%); m.p. 221-222 C; Rf = 0.23 (70% EtOAc/n-Hexane); IR (KBr): 3131, 3056,
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2923, 2851, 1699, 1497, 1465, 1333, 738 cm-1; H NMR (400 MHz, CDCl3) δ 7.31-7.27 (m,
7
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18H), 7.15-7.11 (m, 18H), 7.04 (s, 4H), 6.91 (t, J = 7.2 Hz, 4H), 6.60 (s, 4H), 5.79 (s, 2H), 5.34
(s, 8H), 5.27 (s, 8H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.9, 141.5, 136.4, 134.4, 128.8,
128.4, 128.4, 127.6, 127.6, 127.0, 121.6, 119.9, 119.0, 118.8, 109.5, 53.7, 41.7, 39.6; HRMS
(ESI) m/z C80H66N16Na (M+Na)+ calcd 1273.5554, found 1273.5542.
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ACKNOWLEDGMENTS
This work was supported by a Research Grant from Burapha University through the
National Research Council of Thailand (39/2557) and the Center of Excellence for Innovation
in Chemistry (PERCH-CIC). R.S. and N.S. are grateful for support through a PhD scholarship
from the Royal Golden Jubilee (R.G.J.). We also thank Thapani Phetchara, Manassawee Janrod
and Teerachart Ngernrod, for their support. Special thanks to Prof Frederick W H Beamish and
Dr Ronald Beckett, Faculty of Science, Burapha University for Their comments and English
corrections.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website, which
contains the 1H and 13C{1H} NMR spectra for the synthesized compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
Rungnapha Saeeng
*E-mail: rungnaph@buu.ac.th
ORCID
Rungnapha Saeeng: 0000-0003-2437-2231
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Natthiya Saehlim: 0000-0002-6329-4363
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NOTES
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There are no conflicts to declare.
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