Reactions of Substituted Indoles with 2,3-Dichloro-1,4-naphthoquinone and Electrochemical Properties of Some 2,3-Substituted 1,4-Naphthoquinones

Article abstract of DOI:10.1134/S1070428019040213

The reactions of 2,3-dichloro-1,4-naphthoquinone with some indoles and thiols were investigated. The resulting nucleophilic substitution products were characterized by spectroscopic methods (FT-IR, ¹H and ¹³C NMR, MS) and microanalys

Full text of DOI:10.1134/S1070428019040213

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 4, pp. 546–553. © Pleiades Publishing, Ltd., 2019.
Reactions of Substituted Indoles with 2,3-Dichloro-
1,4-naphthoquinone and Electrochemical Properties
of Some 2,3-Substituted 1,4-Naphthoquinones
C. Ibisa,* S. Sahinler Aylab, D. Tulegenovaa, and H. Bahara
a Department of Chemistry, Engineering Faculty, University of Istanbul, Istanbul, Turkey
b Department of Chemistry, Engineering Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey
*e-mail: ibiscml@istanbul.edu.tr
Received December 10, 2018; revised December 10, 2018; accepted December 25, 2018
Abstract—The reactions of 2,3-dichloro-1,4-naphthoquinone with some indoles and thiols were investigated.
1
The resulting nucleophilic substitution products were characterized by spectroscopic methods (FT-IR, H and
13C NMR, MS) and microanalysis. The effects of polar and nonpolar solvents on the electronic absorption
spectra and electrochemical properties of some newly synthesized compounds were also studied.
Keywords: 2,3-dichloro-1,4-naphthoquinone, indoles, thiols, nucleophilic substitution, cyclic voltammetry.
DOI: 10.1134/S1070428019040213
The indole core exists in many important drugs
such as Sumatriptan [1]. Indole derivatives with im-
portant biological activities can be isolated from plants
or animals [2–3]. Tryptamine, serotonin, and melato-
nin are most known examples of naturally occurring
indoles. The 3-position of indoles is very active for
electrophilic substitution, which enables synthesis of
substituted indoles [4–7]. Some mono- and bis(in-
dolyl)quinones have been reported in the literature
[8–10]. In addition, 1,4-naphthoquinone scaffold is
used in many electrochemical experiments owing to its
important role in redox systems [11–13].
NH stretching bands were seen at 3415 and 3396 cm–1,
respectively. The molecular ion peaks of 3 and 7 were
observed in their ESI mass spectra at m/z 308 and 322,
respectively. Indolyl-substituted quinones 3 and 7 were
treated with some thiols to allow substitution of the
second chlorine; compounds 5a, 5b, and 8 were thus
synthesized. The 13C NMR spectra of 5a and 5b dis-
played carbonyl carbon signals at δC 166.72, 171.17
and 170.33, 180.84 ppm, respectively. The molecular
ion peak of 8 was observed at m/z 422 in the negative
ion ESI mass spectrum. N,S-Substituted compounds
11a and 11b were obtained in the same way from
chloroquinone 10 [16] and thiols 4a and 4b. In the IR
spectrum of 11a, the quinone and ester carbonyl bands
appeared at 1676 and 1733 cm–1, respectively.
Another 3-substituted indole derivative 13 was syn-
thesized by the reaction of 2,3-dichloro-1,4-naphtho-
quinone (1) with 4-methoxyindole (12). In the 1H NMR
spectrum of 13 the methoxy protons gave a singlet at
δ 4.45–4.50 ppm. Compound 13 reacted 4-fluoroben-
zenethiol (4c) and hexadecane-1-thiol (4d) to produce
sulfides 14a and 14e, respectively. Compound 14a
displayed the protonated molecular ion peak at m/z 428
in the positive ion ESI mass spectrum, and the charac-
teristic NH band of 14b was observed at 3388 cm–1 in
the IR spectrum.
The diversity of 1,4-naphthoquinone reactions con-
tinuously increases and attracts growing attention of
synthetic chemists [14, 15]. The obvious biological
relevance of quinones substituted with indoles
prompted scientists to investigate this type of reac-
tions. In continuation of our studies, we investigated
the behavior of indoles as carbon nucleophiles and
synthesized some new indolyl-substituted 1,4-naphtho-
quinones. The reactions occurred at position 2 if
position 3 was occupied. The substitution reactions
of 2,3-dichloro-1,4-naphthoquinone (1) with some
N-, S-, and O-nucleophiles were studied and discussed
previously [15]. The reactions of 2,3-dichloro-1,4-
naphthoquinone (1) with indole (2) and 2-methylindole
(6) gave 3-substituted indole derivatives 3 and 7
(Scheme 1). In the IR spectra of 3 and 7, characteristic
2,3-Dichloro-1,4-naphthoquinone (1) was also
treated with 3-substituted indoles 15 and 17 to obtain
546

REACTIONS OF SUBSTITUTED INDOLES WITH 2,3-DICHLORO-1,4-NAPHTHOQUINONE
547
Scheme 1.
O
O
N
NH
NH
H
RSH (4a, 4b)
2
SR
Cl
O
O
O
3
5a, 5b
Me
O
N
NH
Me
NH
Me
H
2,4-Me2C6H3SH
6
Cl
SC6H3Me2-2,4
O
O
7
8
O
O
O
H
H
N
Et2NCH2CH2NH2
N
RSH (4a, 4b)
9
NEt2
NEt2
Cl
SR
O
10
11a, 11b
OMe
MeO
O
MeO
O
O
O
N
H
NH
Cl
Cl
NH
RSH (4c, 4d)
12
SR
Cl
O
O
1
13
14a, 14b
COOMe
MeOC(O)
O
N
H
N
15
H
COOMe
O
O
HN
16
CHO
CHO
N
H
N
17
Cl
O
O
18
SR
4e, 4f
SR
O
19a, 19b
4, R = MeOC(O)CH2CH2 (a), BuOC(O)CH2CH2 (b), 4-FC6H4 (c), C16H33 (d), C6H13CMe2 (e), C9H19CMe2 (f);
5, 11, R = MeOC(O)CH2CH2 (a), BuOC(O)CH2CH2 (b); 14, R = 4-FC6H4 (a), C16H33 (b); 19, R = C6H13CMe2 (a), C9H19CMe2 (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 4 2019

IBIS et al.
548
Table 1. Half-wave potentials of the first reduction wave and electrochemical data for some naphthoquinone derivatives
(c = 10–3 M) in DMSO (supporting electrolyte 0.1 M TBAP)
Compound no.
Ep1c, V
Ep2c, V
ΔEp1,a mV
E11/2,b V
1
–0.4038
–0.4059
–0.2293
–0.6972
–0.7009
–0.2742
–0.2275
–0.4996
–0.4906
–1.1620
–0.7310
–0.6641
–1.5880
–1.9090
–0.4578
–0.7400
–1.2060
–1.1850
235
044
068
295
068
112
099
122
090
–0.2861
–0.3839
–0.1955
–0.3995
–0.1955
–0.2180
–0.1782
–0.4383
–0.4458
3
7
11a
11b
13
16
19a
19b
a
ΔEp1 = Epa1 – Epc1
.
b
E11/2 = (Epa1 + Epc1)/2.
1
compounds 16 and 18, respectively. In the H NMR
spectrum of 16, the NH protons gave a singlet at
δ 8.71 ppm, and the molecular ion peak of 16 was
observed at m/z 504 in the positive ion ESI mass spec-
trum. No band assignable to NH stretching vibrations
was present in the IR spectrum of 18, indicating
substitution at the indole nitrogen atom. The reactions
of quinone 1 with tertiary thiols 4e and 4f afforded
previously unknown bis-sulfides 19a and 19b which
showed only one carbonyl carbon signal in the
13C NMR spectrum at δC 180.50 and 179.97 ppm,
respectively, due to symmetric structure of their mole-
cules. In the mass spectra of 19a, the [M + Na]+ ion
peak was observed at m/z 497.
ical parameters were evaluated from the voltammetric
curves obtained over the potential range from 1000
to –2000 mV.
Quinones are known to be reduced in non-aqueous
media to give radical anions and dianions. The reduc-
tion of 2,3-dichloro-1,4-naphthoquinone (1) was seen
as two reversible peaks corresponding to the radical
anion and the dianion redox system at potentials of
–0.4038 V and –1.1620 V, respectively (Fig. 1). In the
·
first step, a semiquinone radical anion (Q–) is formed
by addition of an electron to the quinone molecule. In
the second step, hydroquinone dianion (Q2–) is generat-
ed by addition of an electron to the semiquinone
radical anion [17, 18]. The redox potentials of indolyl-
and sulfanyl-substituted naphthoquinone derivatives
changed depending on the substituent nature, and
additional cathodic and anodic peaks were detected in
the voltammograms due to redox processes involving
the substituents [19]. The cyclic voltammograms of
C-substituted compound 3, 7, and 13 displayed a dif-
ferent profile which did not fit that typical of two
single-electron reversible charge transfer processes
observed for 2,3-dichloro-1,4-naphthoquinone (1).
Three peaks were observed in both cathodic and
anodic regions. The potentials in the first reduction
step for compounds 3, 7, and 13 were Ep1 = –0.1057,
–0.2293, and –0.2742 V, respectively. It can be
attributed to the acidity level of protons settled on the
nitrogen atom [20].
The electrochemical behaviors of compounds 1, 3,
7, 11a, 11b, 13, 16, 19a, and 19b were studied by
cyclic voltammetry in DMSO using 0.10 M tetrabutyl-
ammonium perchlorate as supporting electrolyte at
a potential sweep rate of 100 mV/s. The electrochem-
Current, μA
2
10
0
1
–10
3
–20
–30
–2.0
–1.0
0.0
1.0
Potential, V
The voltammogram of compound 19a showed two
successive one-electron reduction processes typical of
quinones in aprotic media. This can be related to the
lack of labile protons in the molecule. The cyclic volt-
Fig. 1. Cyclic voltammograms of compounds (1) 3, (2) 13,
and (3) 16 in DMSO against 0.1 M Bu4N ClO4 on a glassy
carbon disk electrode; scan rate 0.1 V/s.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 4 2019

REACTIONS OF SUBSTITUTED INDOLES WITH 2,3-DICHLORO-1,4-NAPHTHOQUINONE
549
Table 2. Electronic absorption spectra of some naphthoquinone derivatives in ethanol and chloroform (c = 10–4 M)
λ
max, nm (logε)
Compound no.
ethanol
chloroform
3
246 (5.71), 279 (5.81), 496 (4.38)
221 (5.38), 280 (4.17), 568 (3.20)
212 (6.45), 275 (5.83), 515 (5.02)
225 (4.83), 282 (5.72), 565 (4.83)
237 (4.79), 275 (5.60), 473 (4.79)
257 (6.47), 474 (5.60)
253 (5.39), 283 (5.54), 520 (3.86)
292 (3.47), 482 (3.17)
5a
5b
7
240(6.10), 277 (5.92), 482 (5.24)
240 (5.58), 280 (5.52), 559 (4.57)
244 (5.57), 278 (5.96), 479 (5.11)
235 (5.82), 276 (5.85), 482 (5.01)
221 (5.05), 279 (4.99), 483 (4.13)
230 (6.09), 279 (6.22), 497 (4.58)
221 (5.79), 274 (5.66), 499 (4.74)
221 (5.83), 274 (5.53), 529 (4.51)
217 (4.97), 291 (5.02), 482 (3.94)
253 (4.58), 286 (4.64), 448 (3.99)
10
11a
11b
13
229 (5.84), 277 (5.83), 477 (5.03)
223 (6.73), 275 (6.55), 510 (5.62)
222 (6.00), 274 (5.85), 456 (4.96)
224 (6.05), 272 (5.91), 457 (5.09)
242 (5.59), 288 (5.52), 435 (4.44)
251 (4.82), 278 (4.81), 443 (4.18)
14d
14e
18
19f
ammograms of N,S- and N,N-substituted compounds
11a, 11b, and 16 showed three cathodic peaks. The
electrochemical parameters, including cathodic peak
potentials (Epc1 and Epc2), half-wave peak potentials
(E11/2), and differences between the first oxidation and
reduction potentials (ΔEp) are given in Table 1.
LC/MS/MS spectrometer using the ESI technique. The
prod-ucts were isolated by column chromatography on
silica gel 60 (70–230 µm, Sigma). Thin-layer chroma-
tography (TLC) was performed on silica gel 60 F254
plates (Merck); detection with ultraviolet light
(λ 254 nm). All chemicals were reagent grade and
were used without further purification.
Cyclic voltammetry measurements were performed
in a conventional three-electrode cell using a com-
puter-controlled system of a Gamry Reference 600
Model potentiostat/galvanostat. A glassy carbon disc
was used as a working electrode. The surface of the
The electronic absorption spectra of the synthesized
compounds in polar (ethanol) and weakly polar
solvents (chloroform) were studied (Table 2). The
UV-Vis spectra of all compounds showed four absorp-
tion bands (Fig. 2), in particular a high-energy band at
about λ 240 nm, an intense band at λ ~280 nm, a low-
intensity band at λ 340 nm, and a band in the visible
region at λ ~470 and ~560 nm [21, 22]. The bands at
λ 270 and 290 correspond to π– π* transitions in the
quinoid fragment. Shifts of the absorption maxima to
longer wavelengths and increase of the molar absorp-
tion coefficients were observed in going to a more
polar solvent [21].
Absorbance, arb. units
3
0.8
0.6
EXPERIMENTAL
0.4
0.2
0.0
Melting points were measured using a Buchi B-540
melting point apparatus and are uncorrected. Elemental
analyses were performed on a Thermo Finnigan Flash
EA 1112 elemental analyzer. The IR spectra were
recorded on a Thermo Scientific Nicolet 600 FTIR
spectrometer in the range from 400 to 4000 cm–1. The
2
1
13
1H and C NMR spectra (500 and 125 MHz, respec-
300
400
500
λ, nm
tively) were recorded in CDCl3 on a Varian Unity
INOVA spectrometer. The mass spectra were obtained
on a Thermo Finnigan LCQ Advantage MAX
Fig. 2. Electronic absorption spectra of compounds (1) 10,
(2) 11a, and (3) 11b in methanol (c = 10–4 M).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 4 2019

IBIS et al.
550
working electrode was polished with alumina before
each run. A platinum wire served as the counter
electrode. The reference electrode was an Ag/AgCl
electrode. Electrochemical grade tetrabutylammonium
perchlorate (TBAP) in ultrapure DMSO was used as
supporting electrolyte at a concentration of 0.10 M.
Solutions were purged with nitrogen prior to each run.
Measurements were made over a potential range
between 1 and –2 V with a sweep rate of 0.1 V/s.
123.50, 122.05, 120.01, 112.15, 103.50. Mass spec-
trum: m/z 308 (Irel 100%) [M + H]+. Found, %:
C 70.50; H 3.21; N 4.25. C18H10ClNO2. Calculated, %:
C 70.25; H 3.28; N 4.55.
Methyl 3-{[2-(1H-indol-3-yl)-1,4-dioxo-1,4-dihy-
dronaphthalen-3-yl]sulfanyl}propanoate (5a) was
synthesized from 0.05 g (0.16 mmol) of 3 and 0.019 g
(0.158 mmol) of methyl 3-sulfanylpropanoate (4a)
according to method b. Yield 47.87%, red oil, Rf 0.36
(petroleum ether–CH2Cl2, 1:1). IR spectrum, ν, cm–1:
3408 (N–H), 3053 (CHarom), 2977, 2855 (C–H), 1666
(C=O), 1591 (C=C). 1H NMR spectrum, δ, ppm: 8.14 s
(1H, NH), 7.18 s (1H, NH), 6.48 s (1H, 2′-H), 4.17–
4.07 m (3H, OCH3), 3.78–3.63 m (2H, CH2CO), 3.02–
Reactions of 2,3-dichloro-1,4-naphthoquinone
(1) with nucleophiles (general procedures). a. A mix-
ture of 1.0 g (4.40 mmol) of 2,3-dichloro-1,4-naphtho-
quinone (1), the corresponding nucleophile, and 3 mL
of triethylamine in 30 mL of methylene chloride was
stirred for 2–3 h at room temperature. The color of
the solution quickly changed, and the progress of
the reaction was monitored by TLC. The mixture was
diluted with 30 mL of chloroform, and the organic
layer was washed with water (4×30 mL) and dried
over Na2SO4. The solvent was evaporated, and the
residue was purified by column chromatography on
silica gel.
13
2.98 q (2H, SCH2, J = 7.32 Hz). C NMR spectrum,
δC, ppm: 67.16 (OCH3), 171.17, 166.72 (C=O),
151.76, 135.59, 131.46, 130.20, 129.85, 127.78,
125.80, 122.95, 120.91, 120.77, 119.67, 118.74,
114.66, 112.22, 110.00, 44.83 (SCH2). Mass spectrum:
m/z 390 (Irel 100%) [M]+. Found, %: C 67.43; H 4.30;
N 3.60; S 8.12. C22H17NO4S. Calculated, %: C 67.50;
H 4.38; N 3.58; S 8.19.
b. A mixture of appropriate amounts of the corre-
sponding naphtoquinone derivative and nucleophile
and 1.56 g of sodium carbonate in 30 mL of ethanol
was stirred for 2–3 h at room temperature (TLC). The
color of the solution quickly changed. Chloroform
(30 mL) was added to the mixture, the organic layer
was washed with water (4×30 mL) and dried over
Na2SO4. The solvent was evaporated, and the residue
was purified by column chromatography on silica gel.
Butyl 3-{[2-(1H-indol-3-yl)-1,4-dioxo-1,4-dihy-
dronaphthalen-3-yl]sulfanyl}propanoate (5b) was
synthesized from 0.1 g (0.320 mmol) of 3 and 0.05 g
(0.308 mmol) of butyl 3-sulfanylpropanoate (4b)
according to method b. Yield 31.33%, dark purple oil,
Rf 0.70 (CH2Cl2). IR spectrum, ν, cm–1: 3385 (N–H),
3020 (C–Harom), 2962, 2930 (C–H), 1663 (C=O), 1599
1
(C=C). H NMR spectrum, δ, ppm: 8.60 s (1H, NH),
8.09–7.45 m (8H, Harom), 7.10 s (1H, 2′-H), 4.16–
4.17 m (2H, OCH2), 3.80–3.83 t (2H, CH2CO, J =
6.84 Hz), 2.80-2.83 t (2H, SCH2, J = 6.84 Hz), 0.85–
1.36 m (7H, CH2CH2CH3). 13C NMR spectrum, δC,
ppm: 181.42 (C3), 180.84, 170.33 (C=O), 131.47,
129.84, 127.78, 127.36, 125.93, 125.64, 121.73,
120.08, 119.59, 110.60 (Carom), 67.15 (OCH2), 39.22,
39.16 (SCH2), 31.01, 27.63, 24.25, 21.89 (CH2), 13.10
(CH3). Mass spectrum: m/z 432 (Irel 100%) [M]+.
Found, %: C 69.13; H 5.24; N 3.28; S 7.66.
C25H23NO4S. Calculated, %: C 69.26; H 5.35;
N 3.23; S 7.40.
c. A mixture of 0.5 g (2.2 mmol) of 1, the corre-
sponding nucleophile, and 3 mL of triethylamine in
30 mL of chloroform was stirred for 2–3 h at room
temperature (TLC). The color of the solution quickly
changed. The mixture was diluted with 30 mL of
chloroform, the organic layer was washed with water
(4×30 mL) and dried over Na2SO4, the solvent was
evaporated, and the residue was purified by column
chromatography on silica gel.
2-Chloro-3-(1H-indol-3-yl)naphthalene-1,4-di-
one (3) was synthesized from 1 g (4,404 mmol) of 1
and 0.51 g (4,353 mmol) of indole (2) according to
method a. Yield 73.40%, black solid, mp 151–152°C,
Rf 0.93 (petroleum ether–CH2Cl2, 1:1). IR spectrum, ν,
cm–1 : 3415 (N–H), 3097 (C–Harom), 2923 (C–H), 1679
(C=O), 1586 (C=C). 1H NMR spectrum, δ, ppm:
2-Chloro-3-(2-methyl-1H-indol-3-yl)naphtha-
lene-1,4-dione (7) was synthesized from 1.7 g
(7.487 mmol) of 1 and 1 g (7.623 mmol) of 2-methyl-
1H-indole (6) according to method a. Yield 0.22 g
(31.4%), purple solid, mp 150–151°C, Rf 0.48
(CHCl3). IR spectrum, ν, cm–1: 3396 (N–H), 3019
(C–Harom), 2924, 2850 (C–H), 1679 (C=O), 1591
13
8.16 s (1H, NH), 7.72–8.12 m (8H, Harom.). C NMR
spectrum, δC, ppm: 175.03 (C=O), 142.55, 142.50,
133.64, 133.62, 129.96, 129.95, 129.94, 126.82,
1
(C=C). H NMR spectrum, δ, ppm: 8.24 s (1H, NH),
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REACTIONS OF SUBSTITUTED INDOLES WITH 2,3-DICHLORO-1,4-NAPHTHOQUINONE
551
13
7.72–8.28 m (8H, Harom), 2.30 s (3H, CH3). C NMR
spectrum, δC, ppm: 175.06, 175.04 (C=O), 133.66,
132.93, 129.97, 126.83, 126.17, 121.67, 18.01 (CH3).
Mass spectrum: m/z 322 (Irel 100%) [M + H]+. Found,
%: C 70.90; H 3.74; N 4.41. C19H12ClNO2. Calculated,
%: C 70.92; H 3.76; N 4.35.
OCH3), 3.61–3.53 m (2H, CH2CO), 2.97–2.94 t (2H,
NCH2, J = 7.32 Hz), 2.84–2.60 m (2H, NHCH2), 2.56–
2.51 t (2H, SCH2, J = 7.32 Hz), 1.05–1.02 m (6H,
CH2CH3). C NMR spectrum, δC, ppm: 181.53 (C=O,
ester), 181.69, 180.11 (C=O, quinone), 134.73, 133.96,
132.44, 132.17, 126.73, 126.58 (Carom.), 51.85 (OCH3),
46.78 (SCH2), 42.94 (NCH2, NHCH2), 11.66 (CH3).
Mass spectrum: m/z 391 (Irel 100%) [M + H]+. Found,
%: C 61.27; H 6.67; N 7.20. C20H26N2O4S. Calculated,
%: C 61.52; H 6.71; N 7.17.
13
2-[(2,4-Dimethylphenyl)sulfanyl]-3-(2-methyl-
1H-indol-3-yl)naphthalene-1,4-dione (8) was syn-
thesized from 0.1 g (0.310 mmol) of 7 and 0.042 g
(0.303 mmol) of 2,4-dimethylbenzenethiol according
to method b. Yield 32.39%, purple solid, mp 159–
160°C, Rf 0.53 (CH2Cl2). IR spectrum, ν, cm–1: 3389
(N–H), 3013 (C–Harom.), 2926, 2855 (C–H), 1671
(C=O), 1592, 1565 (C=C). 1H NMR spectrum, δ, ppm:
8.24 s (1H, NH), 6.65–8.19 m (11H, Harom), 2.14 s
Butyl 3-[(3-{[2-(diethylamino)ethyl]amino}-
1,4-dioxo-1,4-dihydronaphthalen-2-yl)sulfanyl]pro-
panoate (11b) was synthesized from 0.1 g
(0.323 mmol) of 10 and 0.052 g (0.320 mmol) of 4b
according to method b. Yield 88.15%, red oil, Rf 0.22
(CHCl3). IR spectrum, ν, cm–1: 3281 (N–H), 2960
(CHarom), 2930 (C–H), 1676 (C=O), 1593 (C=C).
1H NMR spectrum, δ, ppm: 8.05–7.39 m (4H Harom),
7.19 s (1H, NH), 7.01 br.s (1H, NH), 4.19–4.04 t (2H,
OCH2, J = 7.32 Hz), 3.94–3.87 m (2H, NHCH2), 3.58–
3.55 s (2H, CH2CO), 2.98–2.95 m (2H, SCH2), 2.66–
2.60 m (2H, NCH2), 2.55–2.52 m (4H, CH2CH3),
1.67–1.17 m (4H, CH2), 1.04–0.79 m (9H, CH3).
13C NMR spectrum, δC, ppm: 180.39 (C=O, ester),
173.17, 178.92 (C=O, quinone), 133.66, 133.52,
132.81, 131.34, 130.96, 129.86, 127.81, 125.63,
125.58, 125.39 (Carom.), 63.52 (OCH2), 50.70 (SCH2),
45.71, 45.64 (NCH2, NHCH2), 33.15, 32.29, 32.08,
31.47, 30.82, 29.58 (CH2), 12.64 (CH3). Mass spec-
trum: m/z 433 (Irel 100%) [M + H]+. Found, %:
C 63.80; H 7.39; N 6.41. C23H32N2O4S. Calculated, %:
C 63.86; H 7.46; N 6.48.
13
(3H, CH3), 2.29 s (6H, CH3). C NMR spectrum, δC,
ppm: 181.13, 180.93 (C=O), 140.85, 134.37, 133.15,
132.94, 131.20, 130.71, 126.41, 126.18, 119.42,
109.74, 12.57, 12.93 (CH3). Mass spectrum: m/z 422
(Irel 100%) [M + H]+. Found, %: C 76.73; H 4.97;
N 3.40; S 7.61. C27H21NO2S. Calculated, %: C 76.57;
H 5.00; N 3.31; S 7.57.
2-Chloro-3-{[2-(diethylamino)ethyl]amino}naph-
thalene-1,4-dione (10) [16] was synthesized from
0.5 g (2.202 mmol) of 1 and 0.255 g (2.194 mmol) of
N,N-diethylethane-1,2-diamine (9) according to
method c. Yield 71.06%, yellow solid, mp 86–87°C;
published data [16]: 10·HCl, mp 242°C; Rf 0.25
(CHCl3). IR spectrum, ν, cm–1: 3265 (N–H), 2967
(CHarom), 2930 (C–H), 1681, 1611 (C=O), 1594 (C=C).
1H NMR spectrum, δ, ppm: 8.30–7.56 m (4H, Harom),
7.19 s (1H, NH), 7.19 br.s (1H, NH), 3.83–3.80 m (2H,
NHCH2, J = 5.36 Hz), 2.53–2.50 t (2H, NCH2, J =
5.86 Hz), 2.50–2.49 m (4H, CH2CH3), 1.01–0.98 m
(6H, CH3). 13C NMR spectrum, δC, ppm: 180.87,
180.85 (C=O), 145.06, 134.89, 133.07, 132.41, 130.28,
126.84, 126.80 (CHarom), 51.78, 51.77, 46.75, 42.16
(NCH2, NHCH2), 12.21 (CH3). Mass spectrum: m/z
307 (Irel 100%) [M + H]+. Found, %: C 62.51; H 6.19;
N 9.21. C16H19ClN2O2. Calculated, %: C 62.64;
H 6.24; N 9.13.
2-Chloro-3-(4-methoxy-1H-indol-3-yl)naphtha-
lene-1,4-dione (13) was synthesized from 1.0 g
(4.404 mmol) of 1 and 0.65 g (4.416 mmol) of
2-methoxy-1H-indole (12) according to method a.
Yield 72.60%, purple solid, mp 120–121°C, Rf 0.31
(CHCl3). IR spectrum, ν, cm–1: 3404 (N–H), 3019
(C–Harom), 2980 (C–H), 1672 (C=O), 1592 (C=C).
1H NMR spectrum, δ, ppm: 9.59 br.s (1H, NH), 9.07 s
(1H, NH), 8.15–6.79 m (7H, Harom.), 6.40 s (1H, 2′-H),
4.48 s (3H, OCH3). 13C NMR spectrum, δC, ppm:
181.79, 178.69 (C=O), 153.69, 133.68, 133.35, 132.95,
132.94, 130.73, 129.95, 129.92, 126.82, 126.00,
126.26, 125.87, 111.85, 102.81 (Carom), 60.84 (OCH3).
Mass spectrum: m/z 336 (Irel 100%) [M + H]+. Found,
%: C 67.51; H 3.62; N 4.18. C19H12NO3. Calculated,
%: C 67.56; H 3.58; N 4.15.
Methyl 3-[(3-{[2-(diethylamino)ethyl]amino}-
1,4-dioxo-1,4-dihydronaphthalen-2-yl)sulfanyl]-
propanoate (11a) was synthesized from 0.1 g
(0.323 mmol) of 10 and 0.039 g (0.324 mmol) of 4a
according to method b. Yield 42.5%, red oil, Rf 0.30
(CHCl3). IR spectrum, ν, cm–1: 3342 (N–H), 3018
(CHarom), 2971, 2926 (C–H), 1676 (C=O), 1593 (C=C).
1H NMR spectrum, δ, ppm: 8.03–7.40 m (4H, Harom.),
7.19 s (1H, NH), 7.18 br.s (1H, NH), 3.90 s (3H,
2-[(4-Fluorophenyl)sulfanyl]-3-(4-methoxy-1H-
indol-3-yl)naphthalene-1,4-dione (14a) was synthe-
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IBIS et al.
552
sized from 0.055 g (0.162 mmol) of 13 and 0.02 g
(0.156 mmol) of 4-fluorobenzenethiol (4c) according
to method b. Yield 50.67%, purple oil, Rf 0.32
(CHCl3). IR spectrum, ν, cm–1: 3387 (N–H), 3019
spectrum: m/z 504 (Irel 100%) [M]+. Found, %:
C 71.40; H 4.04; N 5.60. C30H20N2O6. Calculated, %:
C 71.42; H 4.00; N 5.55.
1-(3-Chloro-1,4-dioxo-1,4-dihydronaphthalen-2-
yl)-1H-indole-3-carbaldehyde (18) was synthesized
from 1.0 g (4.404 mmol) of 1 and 0.63 g (4.340 mmol)
of 1H-indole-3-carbaldehyde (17) according to method
a. Yield 41.10%, purple solid, mp 169–170°C, Rf 0.33
(CHCl3). IR spectrum, ν, cm–1: 3018 (C–Harom), 1667
1
(C–Harom), 1672 (C=O), 1592 (C=C). H NMR spec-
trum, δ, ppm: 8.40 s (1H, NH), 8.31 br.s (1H, NH),
6.50–8.08 m (11H, Harom), 6.21 s (1H, 2′-H), 4.31 s
(3H, OCH3, J = 7.32 Hz). 13C NMR spectrum, δC,
ppm: 181.36, 181.66 (C=O), 153.84 (C4′), 142.48,
138.16, 132.94, 132.85, 132.79, 132.57, 132.40,
132.33, 131.65, 131.48, 130.41, 126.15, 126.12,
125.76, 125.54, 115.44, 115.27, 113.92, 111.97,
107.48, 102.09 (Carom), 69.14 (OCH3). Mass spectrum:
m/z 428 (Irel 100%) [M + H]+. Found, %: C 69.94;
H 3.36; N 3.08; S 7.67. C25H16FNO3S. Calculated, %:
C 69.92; H 3.76; N 3.26; S 7.47.
1
(C=O), 1578 (C=C). H NMR spectrum, δ, ppm:
10.04 s (1H, CHO), 8.29–7.23 m (8H, Harom), 7.02 s
(1H, 2-H). 13C NMR spectrum, δC, ppm: 184.12 (C=O,
aldehyde), 179.80, 179.37 (C=O, quinone), 139.08,
137.07, 133.90, 133.25, 125.95, 125.94, 122.56,
121.36, 110.34 (Carom). Mass spectrum: m/z 360
(Irel 100%) [M + Na]+. Found, %: C 67.89;
H 3.12; N 4.10. C19H10ClNO3. Calculated, %: C 67.97;
H 3.00; N 4.17.
2-(Hexadecylsulfanyl)-3-(4-methoxy-1H-indol-3-
yl)naphthalene-1,4-dione (14b) was synthesized from
0.050 g (0.148 mmol) of 13 and 0.038 g (0.147 mmol)
of hexadecane-1-thiol (4d) according to method b.
Yield 61.36%, purple solid, mp 75–76°C, Rf 0.34
(CHCl3). IR spectrum, ν, cm–1: 3388 (N–H), 3019
2,3-Bis(2-methyloctan-2-ylsulfanyl)naphthalene-
1,4-dione (19a) was synthesized from 1.0 g
(4.404 mmol) of 1 and 1.4 g (8.732 mmol) of
2-methyloctane-2-thiol (4e) according to method b.
Yield 71.66%, dark purple oil, Rf 0.71 (CHCl3). IR
spectrum, ν, cm–1: 2958, 2930 (C–H), 1674 (C=O),
1
(C–Harom), (C–H), 1653 (C=O), 1592 (C=C). H NMR
spectrum, δ, ppm: 8.40 s (1H, NH), 8.41 br.s (1H,
NH), 8.07–6.82 m (7H, Harom), 4.09 s (3H, OCH3),
3.76–3.74 t (2H, SCH2, J = 7.32 Hz) 1.58–1.18 m
(28H, CH2), 0.82–0.81 m (3H, CH3). 13C NMR spec-
trum, δC, ppm: 178.01, 175.67 (C=O), 162.79, 157.26,
146.89, 142.66, 138.76, 133.92, 132.53, 132.37,
132.07, 132.02, 128.36, 125.82, 121.72, 114.34,
107.34, 101.59 (Carom), 69.59 (OCH3), 44.43 (SCH2),
30.92, 29.46, 28.69, 28.65, 28.60, 28.51, 28.49, 28.35,
28.24, 28.13, 28.04, 27.73, 27.54, 26.29 (CH2), 13.09
(CH3). Mass spectrum: m/z 558 (Irel 70%) [M + H]+.
Found, %: C 75.12; H 8.20; N 2.47; S 5.79.
C35H45NO3S. Calculated, %: C 75.09; H 8.10; N 2.50;
S 5.73.
1
1592 (C=C). H NMR spectrum, δ, ppm: 8.02–7.19 m
13
(4H, Harom), 1.88–1.00 m (38H, CH2, CH3). C NMR
spectrum, δC, ppm: 180.05 (C=O), 154.99, 153.86,
153.48, 132.45, 131.98, 126.09, 126.05 (Carom), 40.51,
38.04, 32.62, 30.65, 29.18, 27.53, 24.16, 24.12, 21.93,
21.67, 21.61, 20.58, 19.13, 17.25, 13.50, 13.46, 13.04,
8.26 (CH2, CH3). Mass spectrum: m/z 497 (Irel 100%)
[M + Na]+. Found, %: C 71.14; H 8.23; S 13.07.
C28H42O2S2. Calculated, %: C 70.84; H 8.92; S 13.51.
2,3-Bis(2-methylundecan-2-ylsulfanyl)naphtha-
lene-1,4-dione (19b) was synthesized from 1.0 g
(4.404 mmol) of 1 and 1.78 g (3.184 mmol) 2-methyl-
undecane-2-thiol (4f) according to method b. Yield
58.55%, dark red oil, Rf 0.86 (petroleum ether–CHCl3,
2:1). IR spectrum, ν, cm–1: 3018 (C–Harom), 2927
Dimethyl 2,2′-(1,4-dioxo-1,4-dihydronaphtha-
lene-2,3-diyl)bis(1H-indole-3-carboxylate) (16) was
synthesized from 1.0 g (4.404 mmol) of 1 and 1.54 g
(8.790 mmol) of methyl 1H-indole-3-carboxylate (15)
according to method a. Yield 78.02%, dark red solid,
mp 139–140°C, Rf 0.40 (CHCl3). IR spectrum, ν, cm–1:
3008 (C–Harom), 2944 (C–H), 1694 (C=O), 1580, 1553
1
(C–H), 1663 (C=O), 1588 (C=C). H NMR spectrum,
δ, ppm: 8.02–7.19 m (4H, Harom), 1.85–1.00 m (50H,
CH2, CH3). 13C NMR spectrum, δC, ppm: 179.97
(C=O), 132.65, 132.50, 132.44, 131.96, 126.09,
125.85, 125.72 (Carom), 38.4, 36.08, 33.38, 30.91,
29.20, 28.68, 28.64, 28.36, 26.96, 26.14, 26.07, 25.69,
21.67, 18.71, 13.39, 13.10, 11.26, 11.16, 10.37 (CH2,
CH3). Mass spectrum: m/z 581 (Irel 100%) [M + Na]+.
Found, %: C 73.07; H 9.70; S 11.60. C34H54O2S2.
Calculated, %: C 73.06; H 9.74; S 11.47.
1
(C=C). H NMR spectrum, δ, ppm: 8.71 s (2H, NH),
8.12–7.17 m (12H, Harom), 3.99–3.80 s (6H, OCH3).
13C NMR spectrum, δC, ppm: 163.51, 164.71 (C=O),
135.11, 134.13, 130.04, 129.91, 126.50, 124.80,
122.81, 122.35, 122.21, 121.05, 120.82, 120.50,
111.41, 110.52 (Carom), 50.36, 50.11, (OCH3). Mass
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REACTIONS OF SUBSTITUTED INDOLES WITH 2,3-DICHLORO-1,4-NAPHTHOQUINONE
553
10. Salas, M., Gomes, M., Gonzalez, F.J., and Gordillo, B.,
FUNDING
J. Electroanal. Chem., 2003, vol. 543, p. 73.
This work was supported by Scientific Research
Projects Coordination Unit of Istanbul University
(project no. 38252).
11. Ibis, C., Sahinler Ayla, S., Dogan, Y., and Ozen, M.,
Synth. Commun., 2014, vol. 44, p. 1614.
12. Ibis, C., Sahinler Ayla, S., Bahar, H., Stasevych, M.V.,
Komarovska-Porokhnyavets, O., and Novikov, V.,
Phosphorus, Sulfur Silicon Relat. Elem., 2015, vol. 190,
p. 1422.
CONFLICT OF INTERESTS
13. Sioda, R.E. and Frankowska, B., Monatsh. Chem.,
The authors declare the absence of conflict of
interests.
2008, vol. 139, p. 881.
14. Ibis, C., Tuyun, A.F., Bahar, H., Sahinler Ayla, S.,
Stasevych, M.V., Musyanovych, R.Y., Komarovska-
Porokhnyavets, O., and Novikov, V., Med. Chem. Res.,
2013, vol. 22, p. 2879.
REFERENCES
1. Freidonk-Mueschenborn, E. and Fox, A.W., Headache,
2005, vol. 45, p. 632.
15. Ibis, C., Shntaif, A.H., Bahar, H., and Sahinler Ayla, S.,
2. Haotian, L., Shiyong, F., Jingchao, C., Ping, Z.,
Bohua, Z., and Weiguo, S., Molecules, 2016, vol. 21,
p. 793.
J. Serb. Chem. Soc., 2015, vol. 80, p. 731.
16. Zee-Cheng, R.K.Y., Podrebarac, E.G., Menon, C.S., and
Cheng, C.C., J. Med. Chem., 1979, vol. 22, p. 501.
3. Kaushik, N.K., Kaushik, N., Attri, P., Kumar, N.,
Kim, C.H., Verma, A.K., and Choi, E.H., Molecules,
2013, vol. 18, p. 6620.
17. Abreu, F.C., Lopes, A.C.O., and Goulart, M.O.F.,
J. Electroanal. Chem., 2004, vol. 562, p. 53.
18. Guin, P.S., Das, S., and Mandal, P.C., Int. J. Electro-
chem. Sci., 2008, vol. 3, p. 1016.
4. Tanoue, Y., Kai, N., Nagai, T., and Noda, M.,
J. Heterocycl. Chem., 2014, vol. 51, p. 364.
19. Dron, P.I., Ramesova, S., Holloran, N.P., Pospisil, L.,
5. Koulori, S., Malamidou-Xenikaki, E., Spyroudis, S., and
Tsanakopoulou, M., J. Org. Chem., 2005, vol. 70,
p. 8780.
and Michl, J., Electroanalysis, 2016, vol. 28, p. 2855.
20. Costa, E.O., Molina, M.T., Abreu, F.C., Silva, F.A.S.,
Costa, C.O., Pinho, W., Valentim, I.B., Aguilera-
Venegas, B., Perez-Cruz, F., Norambuena, E., Oleo-
Azar, C., and Goulart, M.O.F., Int. J. Electrochem. Sci.,
2012, vol. 7, p. 6524.
21. Miranda, F.S., Roncon, C.M., Sousa, M.O.B.,
Silveira, G., and Vargas, M.D., J. Braz. Chem. Soc.,
2014, vol. 25, p. 133
6. Okauchi, T., Itonaga, M., Minami, T., Owa, T., Kitoh, K.,
and Yoshino, H., Org. Lett., 2010, vol. 2, p. 1485.
7. Tanoue, Y., Hamada, M., Kai, N., Sakata, T., Hashi-
moto, M., and Nagai, T., J. Heterocycl. Chem., 2005,
vol. 42, p. 1195.
8. Wang, C. and Sperry, J., Tetrahedron, 2013, vol. 69,
p. 4563.
22. Idriss, K.A., Sedaira, H., Hashem, E.Y., Saleh, M.S.,
and Soliman, S.A., Monatsh. Chem., 1996, vol. 127,
p. 29.
9. Nematollahi, D., Hesari, H., Salehzadeh, H., Hesari, M.,
and Momeni, S., C.R. Chim., 2016, vol. 19, p. 357.
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