Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles as non-competitive antagonists of GluK1/GluK2 receptors

Article abstract of DOI:10.1007/s10973-018-7146-6

This paper reports the thermal stability and thermal degradation of six derivatives of indole by means of TG-DSC (in air) and TG-FTIR (in nitrogen) techniques. The compounds were also characterized by infrared spectroscopy. In addition, IR spectra were ca

Full text of DOI:10.1007/s10973-018-7146-6

Journal of Thermal Analysis and Calorimetry
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Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-
tetrasubstituted indoles as non-competitive antagonists of GluK1/
GluK2 receptors
1
Agnieszka A. Kaczor2,3 • Halina Głuchowska1 • Monika Pitucha4 • Tomasz M. Wr o´ bel2,5 •
Agata Bartyzel
•
2
Dariusz Matosiuk
Received: 16 November 2017 / Accepted: 27 February 2018
Ó The Author(s) 2018. This article is an open access publication
Abstract
This paper reports the thermal stability and thermal degradation of six derivatives of indole by means of TG-DSC (in air)
and TG-FTIR (in nitrogen) techniques. The compounds were also characterized by infrared spectroscopy. In addition, IR
spectra were calculated and compared with the experimental data. In particular, the potential energy distribution analysis
was performed to assign IR signals. The studied compounds are characterized by good thermal stability in oxidizing and
inert atmospheres which is important for potential medical application. Thermogravimetric measurements in air atmo-
sphere showed that the decomposition of compounds proceeds in two or three main stages. The thermal degradation of
compounds is preceded by the melting process. The pyrolysis of samples is a one-step process. Together with the analyses
performed in nitrogen, the FTIR spectra of the evolved gas phase products were recorded. On the FTIR spectra of gaseous
products, only the bands of water, carbon dioxide and carbon oxide molecules are present. In the case of indole derivatives
containing the p-chlorobenzyl substituent in position 1, the bands of anisole, p-chlorotoluene and chlorobenzene also
appear.
Keywords Indole derivatives Á Thermal behaviour Á IR spectra Á PED analysis Á Theoretical computations Á
Non-competitive antagonists of GluK1/GluK2 receptors
Introduction
by excellent binding affinity for various receptors [1, 2].
The indole-based compounds can also exhibit various
biological activities such as anti-inflammatory, analgesic,
antifungal, antimicrobial, insecticidal, antioxidant, antivi-
ral, antidepressant, antiarrhythmic, antihistaminic and
antidiabetic ones. [3–6]. According to the literature, there
are over ten thousand biologically active compounds con-
taining indole core. More than 200 of them were approved
as commercially available drugs or are undergoing clinical
Indole is a well-known and important privileged structure
scaffold found in many natural and synthetic compounds.
This core is recognized as one of the foremost biologically
significant moieties in nature. The indoles are characterized
Electronic supplementary material The online version of this article
(https://doi.org/10.1007/s10973-018-7146-6) contains supplementary
material, which is available to authorized users.
3
&
Agata Bartyzel
agata.bartyzel@poczta.umcs.lublin.pl
Department of Pharmaceutical Chemistry, School of
Pharmacy, University of Eastern Finland, Yliopistonranta 1,
P.O. Box 1627, FI-70211 Kuopio, Finland
1
Department of General and Coordination Chemistry, Maria
Curie-Skłodowska University, Maria Curie-Sklodowska Sq.
4
Department of Organic Chemistry, Faculty of Pharmacy with
Division of Medical Analytics, Medical University, 4a
Chodzki St., 20093 Lublin, Poland
2
, 20031 Lublin, Poland
2
Department of Synthesis and Chemical Technology of
Pharmaceutical Substances with Computer Modeling
Laboratory, Faculty of Pharmacy with Division of Medical
Analytics, Medical University, 4a Chodzki St., 20093 Lublin,
Poland
5
Department of Drug Design and Pharmacology, Faculty of
Health and Medical Sciences, University of Copenhagen,
Universitetsparken 2, 2100 Copenhagen Ø, Denmark
123

A. Bartyzel et al.
trials [7, 8], e.g., vinblastine (anticancer), indomethacin
anti-inflammatory), arbidol (antiviral), delavirdine (anti-
order to investigate thermal behaviour of indole derivatives
the TG-DSC and TG-FTIR methods were applied. The
compounds were also characterized by infrared spec-
troscopy. In addition, infrared (IR) spectra of the studied
indole derivatives were calculated and compared with the
experimental data. Theoretical vibrational spectra of the
compounds were interpreted in terms of potential energy
distribution (PED) analysis. Shortly, in order to describe the
vibration of a N-atomic molecule using the PED analysis, the
construction of the set of 3N-6 local, linearly independent,
internal coordinates is required [22]. This set represents
stretching, bending and deformation motions of the func-
tional groups or the chosen fragments of the molecule [22].
The availability of such a coordination set instead of the
normal modes causes that the potential energy distribution
matrix, the PED matrix, ceases to be diagonal, but the energy
distribution originating from the motions of particular
functional groups is understandable for the interpreter [22].
The rationale of the performed research results from the
necessity of thermal stability of the compounds under
investigations which is important for their potential
biomedical application.
(
HIV), zafirlukast (anti-asthmatic), pravadoline (analgesic),
bucindolol (b-blocker) and roxindole (schizophrenia)
[
4–6]. The indoles are also used as dyes, pigments, plastics,
fungicides, vitamin supplements, flavour enhancers, and
perfumery [9].
The main aim of this research was the thermal and
spectroscopic characterization of six indole derivatives,
i.e., 5-methoxy-2-(4-methoxyphenyl)-3-methylindole (1),
1
-ethyl-5-methoxy-2-(4-methoxyphenyl)-3-methylindole
2), 1-[(4-chlorophenyl)methyl]-5-methoxy-2-(4-methox-
yphenyl)-3-methylindole (3), 1-ethyl-2-(4-methox-
yphenyl)-3-methylindole (4), 1-ethyl-2-phenyl-5-methoxy-
(
3
-methylindole (5) and 11-ethyl-8-methoxy-6,11-dihydro-
H-benzo[a]carbazole (6) (Scheme 1). The investigated
5
compounds were synthesized in the Fisher indolization
reaction from the respective arylhydrazine hydrochloride
and appropriate ketone in anhydrous boiling ethanol satu-
rated with HCl followed by alkylation with alkyl halide (with
application of sodium hydride). These compounds are a non-
competitive antagonists of kainate GluK1/GluK2 (GluK—
glutamatergic kainate receptors) receptors with low micro-
molar activity, and compound 2 is the most promising from
the series [10, 11]. Non-competitive antagonists of kainate
receptors [10–15] can be considered promising compounds
for the treatment of neurodegenerative diseases [16, 17] as
well as epilepsy [18]. In particular, a non-competitive mode
of action can result in a better safety profile as reported for
non-competitive antagonists of a-amino-3-hydroxy-5-
methyl-4-isoxazolepropionic acid (AMPA) receptors [19].
In the previous studies, we also constructed 3D models of
GluK1 and GluK2 receptors and suggested that indole-
derived non-competitive antagonists can bind in the receptor
transduction domain [11, 14, 15, 20, 21]. In this study, in
Experimental
Synthesis and short description of compounds
1–6
The investigated compounds were synthesized according to
the following procedure: the mixture of 0.05 mol of aryl-
3
hydrazine hydrochloride, 0.05 mol of ketone, 100 cm of
3
anhydrous ethanol and 10 cm of ethanol saturated with
HCl was refluxed for 4 h. The reaction mixture was left
overnight at room temperature. The obtained product was
Scheme 1 The studied indoles
1
23

Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles…
1
TG
2
TG
Exo
1
00
Exo
100
80
60
40
20
0
5
0
–
1
0
DTG
DTG
8
6
4
2
0
0
0
0
0
5
0
–
DSC
DSC
5
5
0
0
0
200
400
600
800
0
0
0
200
400
600
800
Temperature/°C
Temperature/°C
3
4
TG
TG
1
00
100
80
60
40
20
0
Exo
10
5
5
0
–
DTG
DTG
8
6
4
2
0
0
0
0
0
Exo
DSC
0
DSC
5
–5
200
400
600
800
200
400
600
800
Temperature/°C
Temperature/°C
TG
5
TG
6
5
0
–
100
80
60
40
20
0
100
DTG
5
0
DTG
Exo
Exo
8
6
4
2
0
0
0
0
0
DSC
DSC
5
–5
200
400
600
800
200
400
600
800
Temperature/°C
Temperature/°C
Fig. 1 TG, DTG and DSC curves recorded for 1–6 in air atmosphere
N,N-dimethylformamide (DMF). The reaction mixture was
cooled to 0 °C, and 0.8 g of sodium hydride was added
Table 1 Results of the melting process
-1
-1
Sample
Tonset/°C
T
peak/°C
DH
m
/J g
m
DH /J mol
(
50% oil suspension). After 30 min of mixing, a solution of
3
1
2
3
4
5
6
137
115
124
140
100
117
141
118
127
143
104
122
82.21
71.92
48.94
82.64
71.02
69.51
21.98
21.23
19.14
21.91
18.83
19.26
0.012 mol of alkyl halide in 20 cm of anhydrous DMF
was added dropwise. The reaction was allowed to continue
at room temperature for 3 h. The mixture was filtered, and
3
30–40 cm of water was added to the filtrate. The obtained
precipitate was filtered off and purified by crystallization
from ethanol and washed with n-hexane. The detailed
physicochemical and spectral properties of the investigated
compounds were described in the previous paper [10].
filtered and purified by crystallization from ethanol and
washed with n-hexane. In the next step, 0.01 mol of the
3
indole derivative was dissolved in 30 cm of anhydrous
123

A. Bartyzel et al.
Table 2 Thermal analysis data for compounds 1–6
Complex Atm Temperature range/°C
100
1
2
3
4
5
6
T
peak/°C
Mass loss/%
56.98
8
6
0
0
1
Air
222–398
98–652
348
3
421; 548 43.02
350; 373 98.51
N
2
207–410
205–398
2
Air
339
89.97
5.81
2.73
40
20
0
3
5
98–537
87–787
503; 515
600
N
2
193–360
251–435
331; 346 98.46
383 70.40
542; 598 29.58
3
4
Air
4
35–612
0
100
200
300
400
500
600
700
N
2
234–444
182–381
379
309
503
559
99.00
88.73
10.40
0.84
Temperature/°C
Fig. 2 TG curves of 1–6 in nitrogen
Air
3
5
81–540
40–570
and enthalpy of indium standard. The studies in inert
atmosphere were carried out using the TGA Q5000 anal-
yser (TA Instruments, New Castle, Delaware, USA). The
compounds (15.14–29.69 mg) were heated in an open
N
2
167–334
182–384
256; 344 99.52
5
6
Air
315
544
299
363
543
360
95.93
4.07
4
84–603
N
2
164–310
217–390
99.94
95.09
4.90
platinum
crucible
from
ambient
temperature
-1
Air
3
(* 23–25 °C) to 700 °C in flowing nitrogen (25 cm min ).
4
63–575
Simultaneously with the TG analysis in nitrogen, the infrared
spectra of gaseous products were recorded using the Nicolet
6700 FTIR spectrophotometer (Thermo Scientific) in the
N
2
200–370
99.93
Atm atmosphere of analysis, Tpeak DTG peak temperature (maximum
change of mass)
-
1
-1
spectral range of 600–4000 cm with a resolution of 4 cm
and 6 scans per spectrum. ATR-FTIR spectra were collected
using the Thermo Scientific Nicolet 6700 FTIR spectrometer
equipped with a Smart iTR diamond ATR accessory in the
Methods and physical measurements
-1
The thermal behaviour of compounds was studied in air
and nitrogen atmospheres. The thermal stability and
decomposition in oxidizing atmosphere were determined
using the Setaram Setsys 16/18 derivatograph. The TG and
DSC curves were recorded in temperature range between
range from 4000 to 500 cm . The samples were placed
directly on the diamond crystal of ATR accessory, and the
spectra were obtained from 16 scans taken at a resolution of
-
1
4 cm and normalized.
3
0 and 800 °C. The samples (6.18–7.56 mg) were heated
Computational studies
-
1
in a ceramic crucible at the heating rate of 10 °C min in
flowing air (v = 0.75 dm h ). The temperature and heat
3
-1
Energy and geometry of compounds 1–6 were optimized
with the B3LYP DFT method (DFT—density functional
flow of the instrument were calibrated by the melting point
1
3
0.15
0.25
0
.20
.15
.10
.05
.00
0
.10
0
0
.05
0
3
0.0
30.0
20.0
10.0
0
2
0.0
0.00
0
4
000
4
000
10.0
3000
3000
2000
2000
1
000
1000
Fig. 3 3D FTIR spectra of pyrolysis products during the thermal degradation of 1 and 3
1
23

Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles…
T = 360 °C
Results and discussion
Thermal behaviour of 1–6
The TG-DSC curves providing information about the
thermal properties of 1–6 are shown in Fig. 1. As it can be
seen in the TG curves, the compounds are characterized by
good thermal stability, which is a very important parameter
for their potential application as drugs. The first changes
are recorded on the DSC curves as endothermic peaks at
temperature 100–140 °C. These peaks are not accompanied
by a mass loss and can be attributed to the melting process.
They are roughly similar to the values reported earlier and
determined using a Boetius apparatus [10]. The melting
anisole
point onset temperature (Tonset), peak temperature (Tpeak
)
corresponding to each peak, and enthalpy of fusion taken
from the DSC curves for all compounds are listed in
Table 1. The melting peaks are sharp which indicates that
the compounds were probably synthesised as pure, crys-
talline substances [31–33]. Generally, the substitution of
the pyrrole hydrogen atom in position 1 leads to a
decreased melting point. The exception is compound 4
where the melting point is comparable to that of compound
p-chlorotoluene
1
. This can be a result of a lack of a substituent in the
5-position of the indole core.
The decompositions of the compounds in air are two- or
chlorobenzene
three-step processes that are noted on the TG curves (see
Fig. 1). For all compounds, the major mass loss
(56.98–95.93%) occurs in the first stage which starts at
183–251 °C (Table 2). Taking into account the initial
temperature of the decomposition processes, the following
relative thermal stability order: 5 = 4 \ 2 \ 6 \ 1 \ 3 can
be established. As can be observed, the substitution of
hydrogen attached to nitrogen atom with the ethyl group
decreases the combustion temperature of compounds while
the p-chlorobenzyl substituent stabilizes the molecule and
increases the decomposition temperature of 3 in air com-
pared to 1. In the case of compounds 1 and 3, probably
during the first stage the substituents of the indole core are
broken off and combusted. The theoretical values of the
indole residue (C H N) are 43.82 and 29.95% while the
4
000
3500
3000
2500
2000
1500
1000
500
Wavenumber/cm–1
Fig. 4 FTIR spectrum of volatile products of thermal decomposition
of 3 recorded at 360 °C and the spectra of anisole, p-chlorotoluene
and chlorobenzene
8
7
theory) and the 6-311G??(2df, 2pd) basis set of Gaus-
sian09 software [23]. Gaussian09 was also used to calcu-
late IR spectra. The computed IR spectra were corrected
using the scaling factor of 0.962 as recommended for this
level of theory [24]. Moreover, the computed vibrational
frequencies have been unambiguously assigned by means
of the potential energy distribution (PED) analysis of all
the fundamental vibration modes by using VEDA 4 pro-
gram [25, 26] as described previously [27–30].
experimental ones are equal to 43.03 and 29.60% for
compounds 1 and 3, respectively. The formed products are
unstable and immediately undergo complete destruction
and combustion accompanied by a significant exothermic
effect. The samples are fully decomposed at 612–652 °C. It
is worth mentioning that for compound 1 on the DTG curve
two maxima are visible during this stage, but this is not
clearly indicated on the TG curve. The remaining com-
pounds are almost completely decomposed during this step
(more than 85% of overall mass is lost), and the formed
residues are combusted during one (5 and 6) or two (2 and
123

A. Bartyzel et al.
Table 3 Experimental and
computed IR frequencies and
PED assignment of signals for
compound 2 (the most
Experimental
Computed
Raw
Scaled
PED
promising compound within the
studied series)
3241
3117
3092
3089
3075
3068
3061
3059
3056
3015
3005
3004
2985
2982
2949
2939
2935
2922
2895
2885
1595
1587
1549
1543
1520
1480
1456
1454
1448
1445
1440
1439
1438
1436
1425
1423
1417
1391
1367
1358
1347
1322
1304
1286
1275
1268
1253
1228
1213
mCH (99)
mCH (94)
mCH (92)
mCH (99)
mCH (99)
mCH (92)
mCH (94)
mCH (99)
mCH (92)
mCH (99)
mCH (92)
mCH (99)
mCH (83)
mCH (100)
mCH (88)
mCH (99)
mCH (99)
mCH (92)
mCH (93)
mCC (60)
mCC (31)
mCC (19)
mCC (35)
mCC (45)
3215
3211
3197
3189
3182
3180
3177
3135
3124
2
996 (m)
951 (m)
3123
3
103
100
3
2
3066
055
3
2
1
1
1
1
1
1
1
1
1
830 (w)
898 (vw)
868 (vw)
835 (vw)
612 (m)
588 (w)
576 (w)
562 (w)
506 (m)
481 (s)
3051
3037
3009
2999
1658
1650
1610
1604
1580
1538
dHCC (12)
1
1
513
510
dHCH (53)
dHCH (45)
1
448 (s)
1507
dHCH (61), CHCOC (10)
dHCH (12)
1502
1497
1496
1495
dHCH (70)
dHCH (75), CHCOC (16)
dHCH (78), CHCOC (14)
dHCH (72), CHCCN (15)
mCC (33), dHCC (10)
dHCC (76)
1
431 (m)
1493
1
1
481
479
1418 (m)
1386 (m)
1377 (w)
1366 (m)
1351 (m)
1473
1446
1421
1412
1400
dHCC (10), dHCH (48)
mCC (32), dHCC (22)
dHCC (17)
dHCH (82)
dHCH (15), CHCNC (30)
mNC (26)
1
374
1
307 (m)
286 (s)
1356
1337
mCC (33), dHCC (12)
dHCC (72)
1
1
1
325
318
dCCC (10)
mCC (17), dCCC (11)
dHCC (22), CHCNC (10)
mCC (28), mOC (32)
mCC (11), dHCC (10)
1
246 (s)
1303
1276
1
231 (vs)
1
261
1
23

Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles…
Table 3 continued
Experimental
Computed
Raw
Scaled
PED
1
1
1
202 (s)
182 (m)
171 (s)
1251
1213
1205
1203
1167
1159
1155
1153
1130
1128
1122
1091
1054
1027
1024
986
955
932
919
914
892
853
835
829
800
779
776
766
755
750
732
723
672
649
629
617
608
574
553
530
499
469
452
430
417
389
352
345
324
299
255
mOC (20), dHCC (28)
mOC (26)
dHCH (17), CHCOC (58)
dHCH (10),), CHCOC (32)
dHCC (51)
1201
1
142 (m)
108 (m)
1198
1
174
173
mCC (15), dHCC (36)
dHCH (29), CHCOC (67)
dHCC (26)
1
1
1166
134
1
dHCC (25)
1
072 (s)
1096
1067
mCC (19), CHCCN (39)
mOC (64)
1
035 (vs)
1
064
mOC (53), dHCC (13)
dCCC (43)
1003 (w)
963 (vw)
948 (w)
1025
993
CHCCC (70), CCCCC (13)
CHCCC (71)
969
9
9
55
50
mCC (44), dCCC (15)
mCC (45), dCCN (12)
CHCCC (85), CCCCC (11)
CHCCC (71)
8
8
8
8
7
95 (m)
48 (m)
33 (s)
927
887
868
862
832
CHCCC (65)
18 (s)
CHCCC (54), COCCC (17)
CHCCC (100)
94 (vs)
8
10
CHCCC (48)
7
75 (m)
807
mCC (24), mOC (14), CHCCC (11)
CHCCC (84)
797
785
780
mNC (11), CHCCN (10)
mCC (13), dCCC (12)
CCCCC (69)
7
38 (w)
02 (m)
761
752
7
CCCCC (34)
6
99
CCNCC (34)
6
6
6
6
5
5
5
58 (w)
30 (m)
17 (w)
06 (m)
83 (w)
64 (w)
26 (vw)
675
654
642
632
597
575
551
mNC (11), CCNCC (12)
dCCC (11)
dCCC (31), CCNCC (10)
CHCCC (14), CCCCC (34), COCCC (20)
dCCC (12), dOCC (11)
COCCC (10)
dCCC (14), dCOC (21)
COCCC (20)
519
488
470
447
433
404
366
359
337
311
265
dOCC (21), dCOC (18)
dCCN (21)
CHCCC (11), CCCNC (14), CCCCC (36), COCCC (13)
CHCCC (32), CCCCC (58)
dCOC (10)
dCCN (23), CCNCC (10)
dCOC (10), COCCC (11), CCCCC (10)
dCCC (12), CCCCN (15), COCCC (16)
dCNC (26), CHCCN (10)
dOCC (20), dCOC (13), CCCNC (10)
123

A. Bartyzel et al.
Table 3 continued
Experimental
Computed
Raw
Scaled
PED
2
2
2
1
1
1
50
28
13
95
90
47
241
219
205
188
183
141
91
CHCOC (64)
dOCC (14), CHCOC (10), CHCCN (13)
mCC (19), dCCC (11)
dCNC (19), CHCCN (11)
dOCC (13), CCCNC (14)
dCCC (10), CCOCC (10)
95
81
67
60
55
37
32
CCOCC (55)
78
CCOCC (25), CCCCN (35)
64
CCOCC (27), CCCNC (11), CCCCN (22)
CNCCC (44), CCCCC (10)
58
53
CCOCC (13), CCCNC (39)
36
dNCC (14), dCCC (16), CCNCC (18), CNCCC (22)
CCNCC (18), CNCCC (13), CCCCC (23)
31
s Strong, m medium, w weak, v very, br broad, sh shoulder, m stretching, d bending in plane, C torsional
vibrations
4
) steps. Compounds 4, 5 and 6 are fully combusted at a
for stretching and deformation vibrations, respectively
[31, 32, 34]. Probably other compounds such as indole can
be condensed in the transfer line and do not reach the
detector. In the case of compound 3, at a temperature
between 340 and 420 °C of the pyrolysis process on the
FTIR spectra of evolved gases, several bands in the range
temperature of 570–603 °C. In the case of 2, it was found
that under the measuring conditions a small amount of
unburnt organic matrix remains (1.49%).
Thermal behaviour of 1–6 was also studied in nitrogen
atmosphere (see Fig. 2). The order of thermal stabilities in
inert and oxidizing atmospheres is similar; taking into
account the initial temperature of the decomposition pro-
cesses under nitrogen stream, the following relative ther-
mal stability order: 5 & 4 \ 2 \ 6 \ 1 \ 3 can be
established. In contrast to the thermal decomposition in air,
the pyrolysis processes start at a lower temperature (about
-
1
2700–3100 and 750–1800 cm
were recorded. These
peaks are probably due to the presence of anisole, p-
chlorotoluene and chlorobenzene (see Fig. 4).
Infrared spectroscopy
1
2–22 °C) than the combustion ones. Thermal decompo-
The FTIR spectra of 1–6 are given in Figs. S1–S6. The
observed and calculated frequencies in the infrared spectra
of studied compounds together with their PED assignment
of signals are presented in Tables 3 and S1–S5 (Supple-
mentary material). The scaled computed IR spectra are in
accordance with the experimental values. The strong, sharp
sitions of compounds in nitrogen proceed in one major
mass loss step and similar to the combustion, the com-
pounds are almost completely burnt (for compound 2 the
residue after the pyrolysis is 1.54%). The total pyrolysis of
the compounds can be associated with the presence of
methoxy groups as observed for other compounds con-
taining such substituent [30, 31]. Simultaneously with the
TG analysis in nitrogen, the FTIR spectra of gaseous
products were recorded. The FTIR spectra of gaseous
products evolved during the decomposition of compounds
-
1
peak at 3379 cm in the FTIR spectrum of 1 is charac-
teristic of m(N–H) vibrations of the pyrrole ring. This is
consistent with the literature data; the indoles unsubstituted
in the l-position (N) give a sharp absorption peak in the
-
1
range 3500–3300 cm
[35–40]. This band was not
1 and 3 are given in Fig. 3. In the spectra of gaseous
products, except for the compound 3, only the bands
characteristic of water, carbon monoxide and carbon
recorded in the spectra of other studied compounds due to
the substitution of hydrogen atom in position 1 by ethyl or
-
1
4-chlorobenzyl group. The peaks at 3100–2990 cm can
be assigned to the C–H stretching vibrations of the aro-
matic bonds. The symmetric and asymmetric C–H
stretching bands of the methyl/ethyl groups are observed in
-
1
dioxide were present. The peaks at 2240–2400 cm are
assigned to stretching vibration m(C–O) of carbon dioxide
molecule. In addition, a band at 669 cm is observed due
-
1
-
1
to the deformation vibration of CO . The double peaks in
2
2990–2800 cm . The other important peaks are observed
-1
at the range 1620–1400 cm , and they are mainly due to
-
1
the range 2050–2275 cm correspond to the vibrations of
CO molecule. The characteristic bands of water molecules
the stretching vibrations m(CC) of indole and benzene rings.
The varying intensity bands observed in the FTIR spectra
-
1
are observed in the range 3450–4000 and 1300–1950 cm
1
23

Thermal and spectroscopic studies of 2,3,5-trisubstituted and 1,2,3,5-tetrasubstituted indoles…
-
1
at 1373–1342 and 1287–1283 cm can be assigned to the
C–N stretching modes of pyrrolic ring. These assignments
are in agreement with the literature [35, 39, 41] and cor-
relate with the theoretical calculations. The remaining
bands characteristic of 1–6 with their detailed description is
given in Tables 3 and S1–S5.
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Acknowledgements The paper was developed using the equipment
purchased within the projects ‘‘The equipment of innovative labora-
tories doing research on new medicines used in the therapy of civi-
lization and neoplastic diseases’’ and ‘‘Enhancement of the Research
and Development Potential of the UMCS Faculty of Chemistry and
the Faculty of Biology and Earth Sciences’’ within the Operational
Program Development of Eastern Poland 2007–2013, Priority Axis I
Modern Economy, operations I.3 Innovation promotion. Calculations
with Gaussian 09 were performed under a computational grant by
Interdisciplinary Center for Mathematical and Computational
Modeling (ICM), Warsaw, Poland, grant number G30-18 and under
resources and licenses by CSC, Finland.
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Open Access This article is distributed under the terms of the
Creative Commons Attribution 4.0 International License (http://crea
tivecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give
appropriate credit to the original author(s) and the source, provide a
link to the Creative Commons license, and indicate if changes were
made.
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