Formyl-and acetylindols: Vibrational spectroscopy of an expectably pharmacologically active compound family

Article abstract of DOI:10.1016/j.saa.2009.08.044

In the peresent paper, indole and its seven derivatives were compared, namely 3-formylindole, 1-methyl-3-formylindole, 1-ethyl-3-formylindole, 3-acetylindole, 1-methyl-3-acetylindole, 1-ethyl-3-acetylindole and 1,3-diacetylindole. The substitution of indole in position 3 with aldehydes and with alkyl groups cause only minor changes in the molecular geometry, however, substantially larger alterations are found in the charge distribution and in the vibrational force constants. The appearance of the aldhyde groups increased the degree of association as it was observable on the shape of infrared NH stretching band and its shifts. The alkyl substitution shifts the aldehyde carbonyl stretch band frequencies to somewhat higher values. The effect of the second acetyl group in position 1 is not comparable with those of the 1-alkyl groups. The latter effect is observable in the molecular geometry, however, it is more pronounced in the changes of the net charge distribution, the vibrational force constants and the infrared spectra.

Full text of DOI:10.1016/j.saa.2009.08.044

Spectrochimica Acta Part A 74 (2009) 1031–1045
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Formyl- and acetylindols: Vibrational spectroscopy of an expectably
pharmacologically active compound family
Ferenc Billesa,d, Paula Veronica Podeab, Ildikó Mohammed-Zieglerc,∗
,
Monica Tos¸ ab, Hans Mikoschd, Dan-Florin Irimieb
a Department of Physical Chemistry and Material Science, Budapest University of Technology and Economics, H-1521 Budapest, Budafoki út 8, Hungary
b Department of Biochemistry and Biochemical Technology, Babes¸-Bolyai University, Cluj, Romania
c Gedeon Richter Plc, H-2510 Dorog, Esztergomi út 27, Hungary
d Institute for Chemical Technologies and Analysis, Vienna University of Technology, A-1060 Wien, Getreidemarkt 9, Austria
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 May 2009
Accepted 20 August 2009
In the peresent paper, indole and its seven derivatives were compared, namely 3-formylindole,
1-methyl-3-formylindole, 1-ethyl-3-formylindole, 3-acetylindole, 1-methyl-3-acetylindole, 1-ethyl-3-
acetylindole and 1,3-diacetylindole. The substitution of indole in position 3 with aldehydes and with
alkyl groups cause only minor changes in the molecular geometry, however, substantially larger alter-
ations are found in the charge distribution and in the vibrational force constants. The appearance of the
aldhyde groups increased the degree of association as it was observable on the shape of infrared NH
stretching band and its shifts. The alkyl substitution shifts the aldehyde carbonyl stretch band frequen-
cies to somewhat higher values. The effect of the second acetyl group in position 1 is not comparable
with those of the 1-alkyl groups. The latter effect is observable in the molecular geometry, however, it is
more pronounced in the changes of the net charge distribution, the vibrational force constants and the
infrared spectra.
Keywords:
Indole derivatives
Raman
FT-IR
Acetyl
Formyl
Normal coordinate analysis
© 2009 Elsevier B.V. All rights reserved.
1. Introduction
This was the reason of our interest in 3-formyl and 3-acetyl
derivatives of indole.
Indole derivatives are present in both animals and plants. The
most important compound of this group is tryptophan, an essen-
tial amino acid in the human diet, that is a 3-substituted indole.
Important alkaloids, like serotonin and tryptamin are also indols
substituted in position 3. Indole-3-carbinol can be found in some
vegetables (like cabbage) and its anticarcinogenic and antioxidant
effects are subjects of research [1]. An other important indole
derivative is the indole-3-acetic acid, a phytohormone, coordi-
nateing several growing processes of plants [2]. It seems that the
biological activity of the indole derivatives is in connection with
the nature of substituent in position 3, on the pyrrole ring.
Similarly, some highly selective drugs contain indole structure,
like Sumatriptan and Ondansetron. The first one is for treatment of
migraine, the latter one is used for the suppression of the nausea
and vomiting, caused by cancer chemotherapy and radiotherapy
[3]. Some other drugs also have indole structure, e.g. indomethacin
used for the treatment of rheumatoid arthritis and LSD with high
hallucinogenic activity.
The vibrational spectra of the parent molecule, the indole, were
several times discussed during the last 50 years. Here we mention
some of them. Millich and Becker [4] synthesized several indole
derivatives and measured their infrared spectra in the CH, NH and
C
O stretching regions and compared them to that of indole. Lautié
et al. [5] studied both infrared and Raman spectra of indole and its
deuterated derivatives. They also gave curves approximate assign-
ments of the observed spectral bands. In 1986, two articles delt
with the vibrational spectroscopy of indole in the same journal
issue. Suwaiyan and Zwarich [6] presented the infrared and Raman
spectra with approximate assignment but only for the parent com-
pound. Takeuchi and Harada [7] carried out normal coordinate
analysis of the indole molecule already in 1986, vibrational force
constants were presented and the calculated vibrational frequen-
cies were compared with the experimental ones of Lautié et al.
[5]. In 1988, Collier [8] already applied semiempirical (AM1) cal-
culations for the assignment of the indole spectra and compared
them with his experimental results. In the 90s, ab initio frequency
calculations were also used for the interpretation of the indole spec-
tra. Majoub and Vergoten [9] applied the HF model with 3-21G
basis set and obtained the optimized geometry, the complete force
constant matrix, the assignment (potential energy distribution) of
the vibrational spectra, even for some deuterated derivatives of
∗
Corresponding author. Tel.: +36 203824958.
E-mail addresses: fbilles@mail.bme.hu (F. Billes), mohazihu@yahoo.com
(I. Mohammed-Ziegler), hans.mikosch@tuwien.ac.at (H. Mikosch).
1386-1425/$ – see front matter © 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.saa.2009.08.044

1032
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
indole. Barstis et al. [10] observed the applicability of modern spec-
troscopic methods in the studies of the excited state vibrational
spectra of indole. In this work, the jet-cooled resonant two-photon
ionization (R2PI) was used with time-of-flight (TOF) mass spec-
trometric detection. Klots and Collier [11] studied in detail the
experimental infrared and Raman spectra of indole both in vapour
and liquid phase. Walden and Wheeler [12] already applied DFT
calculations with B3LYP functional and 6-311G(d) basis set for
the frequency calculations of the indole molecule. Collier et al.
[13] calculated vibrational frequencies of some bicylic molecules,
including those of indole. However, in this article benzofuran was
in the focus. El-Azhary [14] used DFT method, the B3LYP functional
with 6-31G** basis set for the calculation of vibrational frequencies
of seven heterocyclic molecules, including indole. The quantum
chemically calculated force field was scaled to experimental fre-
quencies taken from the literature. Xue et al. [15] carried out DFT
calculations for computing the vibrational frequencies of indole,
applying different functionals, e.g. B3LYP, B3PW91, all of them with
6-31G** basis set. Sundaraganesan et al. [16] calculated molec-
ular geometric parameters and vibrational frequencies of indole,
7-azaindole and 5-aminoindole with HF and B3LYP functionals and
6-311++G(d,p) basis set. They also presented the interpretation of
the calculated normal frequencies.
Some papers report on the indole ions. Unterberg et al. [17] stud-
ied experimentally the indole cation and the indole + water cation
using IR/PIRI and IR photodissociation spectroscopy and also the-
oretically with ab initio calculations. Jalbout et al. [18] calculated
the Rydberg electron transfer of an indole–water dimer anion.
Other articles present reactions of indole. Zhou and Liu [19]
investigated the role of tautomerism of indole in the thermal
degradation of the compound with DFT B3LYP/6-31G** method.
Yurtsever and Yurtsever [20] applied a similar DFT method for sim-
ulation of the polymerisation of indole. Smith and Liu [21] studied
the indole tautomers (2H- and 3H-indole) in the same manner.
Several articles dealt with the vibrational spectroscopy of indole
derivatives. Barstis et al. [22] studied 4-, 5- and 6-fluoroindols in
detail. Their excitation spectra were measured using jet-cooled
one-color resonant two-photon ionization (IC R2PI) time-of-flight
mass spectrometry, and the ground state infrared and Raman spec-
tra were also recorded. HF/3-21G calculations were also carried
out for assignment of the fundamental vibrational frequencies.
Results of indole derivatives were compared with those of the
parent compound [10].
acetylindole and 1,3-diacetylindole (see Fig. 1). Thus, one can
observe different substituent effects. Beside the simple substituent
effect on indole, the change from formyl to acetyl substitent in posi-
tion 3 gives the possibility to study the effect of the additional
methyl group on different properties of the molecular skeleton.
With the change of the substituent in position 1 from hydrogen
to ethyl group one can follow the stepwise change of the molecular
properties. Finally, a radical change in position 1 can cause some
peculiar results.
2. Experimental
2.1. Preparation of the studied indole derivatives
3-Formylindole (indole-3-carboxyaldehyde) was prepared with
the help of the complex, formed between phosphorus oxychlo-
ride and dimethylformamide. Phosphorus oxychloride (10 mL) was
added drop by drop to ice-cooled dimethylformamide (30 mL), fol-
lowed by addition of indole (100 mmol). This mixture was stirred at
100 ◦C for 2 h and then poured onto 500 g of ice. The pH value of the
mixture was set to 6 by addition of saturated aqueous NaOAc solu-
tion and it was extracted with toluene (200 mL, four times). The
combined toluene solutions were dried over anhydrous Na2SO4,
and then concentrated to a volume of 50 mL by distillation under
reduced pressure. Chromatography on silica gel using toluene as
eluent followed by recrystallization from ethanol or hexane yielded
the desired compound (Scheme 1).
Synthesis of the intermediers 1-(1H-indol-3-yl)ethanone and
1-(5-bromo-1H-indol-3yl)ethanone, respectively [27]. SnCl4 was
added (1.44 mL, 12 mmol) in a single portion via syringe to a
stirred solution of indole (1.17 g, 10 mmol) in CH2Cl2 (20 mL) under
argon at 0 ◦C. After the ice bath was removed, the mixture was
stirred at room temperature for 30 min, and then acetyl chloride
(10 mmol) was added in small portions to the suspension, followed
by nitromethane (15 mL). The mixture was stirred for 2 h at room
temperature under argon atmosphere, after quenching it with ice
and water (30 mL) (Scheme 2).
The N-alkyl derivatives were synthesized through alkylation of
both derivatives with alkyl iodide in presence of a strong base
(Scheme 3).
2.2. Recording of the spectra
The infrared spectra were recorded on a Nicolet Magna 75 IR
spectrometer at 2 cm−1 resolution and with the coadditon of 250
individual spectra in the 4000–400 cm−1 region in KBr discs.
The Raman spectra were measured on Bruker RFS 100/S FT-
Raman spectrometer at 4 cm−1 resolution and with the coaddition
of 2000 single spectral scans in the 3500–200 cm−1 region. The
spectra were excited using the 1064 nm band of a Nd–YAG laser
with 400 mW output power. The germanium detector was cooled
with liquid nitrogen.
Arjunan et al. [23] recorded the infrared and Raman spectra
of 5-aminoindole. The assignment of the normal frequencies was
achieved without quantum chemical calculations using normal
coordinate analysis. Later, Sundaraganesan et al. [16] also dealt in
their aforementioned article with the vibrational spectroscopy of
5-aminoindole basing the assignment of vibrational fundamentals
on high level quantum chemical calculations.
Carney and Zwier [24] applied modern experimental meth-
ods to characterize the hydrogen-bonding topologies of indole–
The overlapping frequencies were resolved by the PCCP soft-
ware [28].
(water)1,2
,
1-methylindole–(water)1–3
,
and 3-methylindole–-
(water)1 clusters. A combination of resonant two-photon ioniza-
tion (R2PI), resonant ion-dip infrared spectroscopy (RIDIRS), and
infrared-ultraviolet (IR-UV) hole-burning spectroscopy were used.
Besides, the vibrational frequencies and band intensities were
computed with the Becke3LYP/6-31+G* functional and basis set.
Suwayan and Morsy [25] recorded polarized infrared spectra
and Raman spectra of melt cryatalline 5-methoxyindole, and calcu-
lated their vibrational spectroscopic properties by HF/3-21G.
Morzyk-Ociepa et al. [26] determined the crystal structure and
recorded the infrared spectrum of indole-2-carboxylic acid.
In the peresent work, indole and its seven derivatives were
studied, i.e. 3-formylindole, 1-methyl-3-formylindole, 1-ethyl-3-
formylindole, 3-acetylindole, 1-methyl-3-acetylindole, 1-ethyl-3-
3. Calculations
For the quantum chemical calculations, the Gaussian 03 pro-
gram package [29] was used with the DFT B3LYP functional and
the 6-311G** basis set. By the first step of the calculations, the opti-
mized molecular geometries, the NBO charges, the Mulliken, and
the atomic net charges were obtained. The second step of the com-
putations gave the vibrational force constants of the molecules, the
calculated fundamental frequencies, the corresponding infrared
and Raman intensities, and the depolarization ratios of the Raman
bands.

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1033
Fig. 1. Optimized structures of the investigated molecules.
The quantum chemical results were elaborated with home-
made programs. Internal coordinates were defined; the force
constants were transformed into this system. Then, the force con-
stants were scaled to the experimental spectra. The scale factors of
the indole molecule were transformed to the derivatives; only for
the internal coordinates, contaning carbonyl group, were defined
new scale factors. After that the PED matrices were calculated, the
stretching group vibrations were distinguished. Finally, based on
Scheme 1. Synthesis rute of 3-formylindole.

1034
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
Fig. 2. Numbering of the atoms in indole and in its substituents.
4. Results and discussion
The calculted data and their interpretation are the subjects of
the following sections. For the calculations and the discussion of the
results, numbering of the atoms in the molecules was needed. Fig. 2
presents the numbering of the atoms of indole (this numbering also
holds for all derivatives), and also illustrates the numbering of the
substituents.
Scheme 2. Synthesis of acetylindole derivatives.
4.1. Molecular geometry
The most important optimized geometric parameters of the
investigated molecules are compared in Tables 1 and 2. These
parameters belong to the heavy atoms of the molecules and of the
substituents, respectively. The full list of the bond length and the
valence angle parameters are collected in the deposited Table S1.
The optimized structures of the molecules are presented in Fig. 1.
The numbering of the atoms of indole and its substituents are
shown in Fig. 2.
Scheme 3. Synthesis of N-alkylindole derivatives.
The substitutions in the indole ring induce drastic changes
in the values of the molecular parameters. It is essential that
the exchange of the hydrogen by carbon increases the distance
ring atom—first substituent atom. However, the substitutions also
the scaled vibrational fundamental frequencies and the calculated
band intensities, infrared and Raman spectra were simulated apply-
ing Lorentz type band contours with 15 cm−1 FWHH.

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1035
Table 1
Some important geometric parameters of indole and its studied formyl and acetyl derivatives.
Geometric
Indole
3-Formylindole
1-Methyl-3-
formylindole
1-Ethyl-3-
formylindole
3-Acetylindole
1-Methyl-3-
acetylindole
1-Ethyl-3-
acetylindole
1,3-Diacetylindole
parametera,b
r (1, 2)
r (2, 3)
r (3, 9)
r (4, 9)
r (4, 5)
r (5, 6)
r (6, 7)
r (7, 8)
r (8, 1)
r (8, 9)
r (1, 10)
r (3, 12)
1.382
1.365
1.382
1.446
1.402
1.387
1.407
1.388
1.395
1.390
1.415
1.007
1.452
1.365
1.382
1.440
1.400
1.380
1.400
1.380
1.390
1.392
1.410
1.451
1.449
1.365
1.382
1.444
1.401
1.388
1.406
1.389
1.397
1.395
1.416
1.460
1.450
1.367
1.382
1.448
1.403
1.387
1.407
1.388
1.395
1.388
1.415
1.007
1.467
1.367
1.382
1.446
1.402
1.388
1.406
1.388
1.396
1.390
1.416
1.451
1.466
1.368
1.383
1.445
1.402
1.388
1.406
1.389
1.397
1.392
1.416
1.463
1.465
1.391
1.367
1.453
1.399
1.389
1.403
1.391
1.394
1.416
1.412
1.410
1.475
1.367
1.436
1.404
1.386
1.408
1.387
1.397
1.379
1.422
1.006
1.079
ϕ (1. 2, 3)
ϕ (2, 3, 9)
ϕ (3, 9, 4)
ϕ (9, 4, 5)
ϕ (4, 5, 6)
ϕ (5, 6, 7)
ϕ (6, 7, 8)
ϕ (7, 8, 1)
ϕ (8, 1, 2)
ϕ (9, 8, 1)
ϕ (8, 9, 3)
ϕ (8, 9, 4)
ϕ (7, 8, 9)
ϕ (2, 1, 10)
ϕ (8, 1, 10)
ϕ (2, 3, 12)
ϕ (9, 3, 12)
109.5
109.6
106.7
134.0
118.5
121.4
121.3
117.1
130.3
109.7
107.2
106.8
119.2
122.5
125.3
125.1
124.8
128.5
110.4
106.4
133.9
118.4
121.3
121.2
117.1
129.8
108.7
107.9
106.6
119.3
122.3
126.2
125.1
125.0
128.6
110.5
106.4
133.8
118.5
121.3
121.3
117.3
130.0
108.5
107.8
106.7
119.5
122.1
125.6
125.8
125.0
128.6
109.8
106.4
134.0
118.6
121.4
121.2
117.1
130.1
109.6
107.2
107.0
119.0
122.7
125.1
125.3
127.0
126.6
110.6
106.1
134.1
118.6
121.4
121.2
117.2
129.7
108.7
107.8
106.8
119.1
122.5
126.1
125.2
127.2
126.7
110.6
106.2
134.1
118.6
121.4
121.2
117.3
129.6
108.4
108.0
106.7
119.2
122.4
127.9
123.6
127.0
126.7
110.6
107.1
134.4
119.1
121.1
121.2
117.5
130.6
109.3
107.1
106.9
118.7
122.3
125.3
125.4
125.8
127.0
106.8
132.9
118.3
121.1
121.6
117.0
130.5
107.9
107.4
107.3
119.8
122.2
126.1
126.0
126.6
126.6
a
Bond lengths in angstroms, valence angles in degrees.
For numbering of the atoms see Fig. 2.
b
cause secondary changes in the parameters. Take a look at the
data in Table 1. The N1–C2 bond is sensitive to the substitu-
tions in position 3. The aforementioned distance decreases by
this substitution, but it is practically independent of the type of
the substituent, and even of the type of the alkyl substituent
in position 1. However, a second acetyl substituent compen-
sates by its −I, −M effect for that of the 3-acetyl group and the
bond length increases this distance of indole. One can observe
just the opposite effect at the C2–C3 bond length. The substitu-
tion does paractically not act at the C4–C5, C5–C6, C6–C7 and
C7–C8 bonds. The changes remain below 0.01 Å. All substitu-
tions increase the C8–N1 bond somewhat with the exception of
the 1-acetyl group, causing more than 0.02 Å additional elonga-
tion. As expected, the length of N1–C10 bond is independent of
the type of the 3-substituent but increases somewhat with the
transition from the methyl to the ethyl group. The substituent
effect of the heavy atom valence angles are small, not higher than
2–3◦.
Table 2
Some important geometric parameters of the substituent groups.
3-Formyl group
Geometric parametera,b
3-Formylindole
1-Methyl-3-formylindole
1-Ethyl-3-formylindole
r (12,f1)
r (12,f2)
ϕ (3,12,f1)
ϕ (3,12,f2)
ϕ (f1,12,f2)
1.216
1.113
125.2
114.4
120.4
1.216
1.113
125.3
114.4
120.3
1.216
1.114
125.3
114.4
120.4
1-Ethyl group
Geometric parametera,b
1-Ethyl-3-formylindole
1-Ethyl-3-acetylindole
1.524
r (10,e2)
ϕ (1,10,e2)
1.531
113.3
114.1
3-Acetyl group
1-Acetyl group
1,3-Diacetylindole
Geometric parametera,b
3-Acetylindole
1-Methyl-3-acetylindole
1-Ethyl-3-acetylindole
Geometric parametera,b
r (12,a1)
r (12,a2)
ϕ (3,12,a1)
ϕ (3,12,a2)
ϕ (a1,12,a2)
1.220
1.523
121.4
118.1
120.5
1.221
1.524
121.5
118.1
120.4
1.221
1.524
121.6
118.1
120.3
1.218
1.521
121.1
118.2
120.8
1.208
1.516
121.0
116.4
122.6
r (10,c1)
r (10,c2)
ϕ (1,10,c1)
ϕ (1,10,c2)
ϕ (c1,10,c2)
a
Bond lengths in angstroms, valence angles in degrees.
For numbering of the atoms see Fig. 2.
b

Table 3
Natural (NBO) atomic charges of indole and its studied formyl and acetyl derivatives (a.ch.u.).
Indole
3-Formylindole
1-Methyl-3-formylindole
1-Ethyl-3-formylindole
3-Acetylindole
1-Methyl-3-acetylindole
1-Ethyl-3-acetylindole
1,3-Diacetylindole
1
2
N
C
−0.5430
0.0030
1
2
N
C
−0.5242
0.0627
1
2
N
C
−0.3709
0.0674
1
2
N
C
−0.3808
0.0655
1
2
N
C
−0.5258
0.0517
1
2
N
C
−0.3725
0.0569
1
2
N
C
−0.3778
0.0481
1
2
N
C
−0.4364
0.0418
3
4
5
6
7
8
9
10
11
12
13
14
15
16
C
C
C
C
C
C
C
H
H
H
H
H
H
H
−0.2875
−0.1857
−0.2223
−0.2028
−0.2392
0.1604
3
4
5
6
7
8
9
10
11
12
13
14
15
16
f1
f2
C
C
C
C
C
C
C
H
H
C
H
H
H
H
O
H
−0.2138
−0.1725
−0.2111
−0.1930
−0.2384
0.1615
3
4
5
6
7
8
9
10
11
12
13
14
15
16
f1
f2
C
C
C
C
C
C
C
C
−0.2141
−0.1725
−0.2107
−0.1935
−0.2434
0.1644
−0.0652
−0.3454
0.2053
0.4014
0.2263
0.2019
0.2007
3
4
5
6
7
8
9
10
11
12
13
14
15
16
f1
f2
C
C
C
C
C
C
C
C
−0.2128
−0.1723
−0.2115
−0.1937
−0.2450
0.1660
−0.0664
−0.1588
0.2055
0.4016
0.2263
0.2018
0.2005
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
C
C
C
C
C
C
C
H
H
C
H
H
H
H
O
C
−0.2136
−0.1731
−0.2131
−0.1947
−0.2397
0.1604
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
m1
m2
m3
C
C
C
C
C
C
C
C
−0.2140
−0.1732
−0.2126
−0.1952
−0.2447
0.1632
−0.0600
−0.3451
0.2044
0.5623
0.2291
0.2008
0.1997
0.2044
−0.5733
−0.6596
0.2082
0.2201
0.2082
0.1961
0.1961
0.2007
3
4
5
6
7
8
9
C
C
C
C
C
C
C
C
−0.2142
−0.1732
−0.2127
−0.1956
−0.2454
0.1661
−0.0600
−0.1559
0.2080
0.5620
0.2288
0..2004
0.1993
0.2044
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
c1
c2
c3
c4
c5
C
C
C
C
C
C
C
C
−0.1756
−0.1771
−0.2010
−0.1894
−0.2179
0.1691
−0.0931
−0.0723
−0.0671
−0.0641
0.3991
0.4048
0.4034
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
e1
e2
e3
e4
e5
e6
0.7331
0.1995
0.2138
0.2005
0.1983
0.1983
0.2009
0.2074
0.4030
0.2264
0.2023
0.2013
0.2044
H
C
H
C
0.2062
0.5633
0.2292
0.2012
0.2003
0.2032
−0.5702
−0.6600
0.2090
H
C
H
C
H
C
0.2121
0.5671
0.2305
0.2024
0.2024
0.2378
−0.5550
−0.6621
0.2116
0.2239
0.2116
−0.5646
−0.6735
0.2198
H
H
H
H
O
H
H
H
H
H
O
H
H
H
H
H
O
C
H
H
H
H
H
H
H
H
H
H
O
C
H
H
H
H
C
H
H
H
H
O
C
H
H
H
O
C
0.2055
0.2045
−0.5457
−0.5495
−0.5496
−0.5749
−0.6596
0.2079
0.2199
0.2079
0.0972
0.0964
0.0962
H
H
H
0.2206
0.2090
m1
m2
m3
H
H
H
0.1970
0.1970
0.2020
e1
e2
e3
e4
e5
e6
H
C
H
H
H
H
0.1962
−0.5738
0.1961
0.2031
0.1992
0.2023
0.1925
−0.5824
H
H
H
H
0.1928
H
H
H
0.2006
0.2002
0.2129
0.2198
0.2338

Table 4
Mulliken atomic net charges of indole and its studied formyl and acetyl derivatives (a.ch.u.).
Indole
3-Formylindol
1-Methyl-3-Formylindole 1-Ethyl-3-formylindole
3-Acetylindole
1-Methyl-3-acetylindole
1-Ethyl-3-acetylindole
1,3-Diacetylindole
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
N
C
C
C
C
C
C
C
C
H
H
H
H
H
H
H
−0.4310
0.0710
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
H
H
C
H
H
H
H
O
H
−0.4292
0.1333
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
C
H
C
H
H
H
H
O
H
−0.4447
0.1411
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
C
H
C
H
H
H
H
O
H
−0.4335
0.1417
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
H
H
C
H
H
H
H
O
C
−0.4332
0.1317
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
−0.4493
0.1397
−0.1742
−0.0535
−0.0988
−0.1019
−0.0600
0.2137
−0.0835
−0.1500
0.1084
0.2112
0.1077
0.0928
0.0906
0.0908
−0.3180
−0.3244
0.1209
0.1312
0.1209
0.1331
0.1331
0.1193
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
−0.4705
0.1527
−0.1793
−0.0540
−0.0983
−0.1031
−0.0597
0.2135
−0.0817
−0.0305
0.1110
0.2111
0.1070
0.0921
0.0898
0.0905
−0.3190
−0.3246
0.1203
0.1305
0.1202
0.1312
−0.3579
0.1309
0.1260
0.1253
0.1264
1
2
3
4
5
6
7
8
N
C
C
C
C
C
C
C
C
−0.4740
0.1478
−0.1515
−0.0707
−0.1052
−0.1108
−0.0498
0.2019
−0.1892
−0.0503
−0.0991
−0.1017
−0.0430
0.1942
−0.1928
−0.0503
−0.0983
−0.1013
−0.0576
0.2157
−0.0900
−0.1500
0.1134
0.2000
0.1063
0.0948
0.0927
−0.1850
−0.0510
−0.0979
−0.1026
−0.0587
0.2216
−0.0967
−0.1054
0.1097
0.1995
0.1061
0.0943
0.0921
−0.1717
−0.0534
−0.0996
−0.1024
−0.0452
0.1922
−0.1589
−0.0503
−0.0908
−0.0985
−0.0262
0.1966
−0.1028
9
−0.0941
9
9
9
−0.0879
9
9
9
−0.0989
0.2247
10
11
12
13
14
15
16
f1
f2
0.2335
10
11
12
13
14
15
16
f1
f2
10
11
12
13
14
15
16
f1
f2
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
0.2310
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
m1
m2
m3
C
H
C
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
e1
e2
e3
e4
e5
e6
C
H
C
10
11
12
13
14
15
16
a1
a2
a3
a4
a5
c1
c2
c3
c4
c5
C
H
C
0.3606
0.1032
0.0826
0.0808
0.0869
0.0880
0.0826
0.1135
0.2027
0.1073
0.0955
0.0941
0.0879
0.1087
0.2132
0.1087
0.0934
0.0920
0.0858
−0.3153
−0.3242
0.1220
0.1232
0.2184
0.1100
0.0965
0.0971
0.1261
−0.3015
−0.3238
0.1255
0.1367
0.1255
−0.3140
−0.3601
0.1406
H
H
H
H
O
C
H
H
H
H
H
H
H
H
H
H
O
C
H
H
H
H
C
H
H
H
H
O
C
H
H
H
O
C
0.0926
0.0920
−0.3080
−0.3116
−0.3114
0.0527
0.0500
0.0498
H
H
H
0.1323
0.1220
m1
m2
m3
H
H
H
0.1345
0.1346
0.1211
e1
e2
e3
e4
e5
e6
H
C
H
H
H
H
0.1323
−0.2758
0.1244
0.1238
0.1163
0.1145
H
H
H
H
H
H
H
0.1406
0.1520

1038
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
Table 5
Selected internal coordinatesa and the value of the adjacent diagonal force constantsb of the studied indole derivatives.
Internal
Indole
3-Formylindole
1-Methyl-3-
formylindole
1-Ethyl-3-
formylindole
3-Acetylindole
1-Methyl-3-
acetylindole
1-Ethyl-3-
acetylindole
1,3-Diacetylindole
coordinatec
r (N1,C2)
r (C3,C9)
r (C9,C4)
r (C4,C5)
r (C5,C6)
r (C6,C8)
r (C7,C8)
r (N1,C8)
7.246
6.460
6.457
7.309
7.265
7.090
6.918
11.858
17.693
5.299
6.417
7.756
6.371
6.578
7.227
7.237
7.042
6.944
11.078
17.306
5.026
6.564
10.831
7.706
6.402
6.611
7.201
7.249
7.019
6.920
10.910
17.203
5.068
5.101
10.762
7.664
6.419
6.599
7.216
7.245
7.025
6.886
10.871
17.177
5.059
4.822
10.769
7.737
6.407
6.561
7.237
7.248
7.068
6.942
11.162
17.314
4.758
6.574
7.675
6.439
6.590
7.212
7.259
7.048
6.916
11.000
17.229
4.784
5.114
7.571
6.488
6.582
7.210
7.257
7.041
6.899
10.959
17.192
4.805
4.813
7.059
6.423
6.692
7.234
7.472
6.975
7.019
10.880
17.963
4.590
5.165
r (C8,C9)
r (C3,H/C12)
r (N1,H/C10)
r (C12,Of1)
r (C12,Oa1)
r (C10,Oc1)
r (C12,Hf2)
r (C7,H16)
10.697
10.665
10.640
5.125
11.229
11.697
4.356
5.099
4.352
5.334
4.343
5.334
5.085
5.094
5.116
5.333
a
The definitions of all internal coordinates and the adjacent diagonal force constants are deposited in Tables S2a, S2b and S2c.
b
c
Diagonal force constants, for stretching coordinates in 102 N m−1
For the numbering of the atoms see Fig. 2.
.
Looking at the values of the molecular parameters belonging to
dencies are similar. See e.g. the net charges of the important C10
and C12 atoms. However, in the case of the 3-formyl substituent
the change from 1-methyl to 1-ethyl shifts the N1 charge in positive
direction, but if the 3-substituent is acetyl, this shift is negative.
the substituents (Table 2), changes in neither the formyl, nor in the
acetyl groups can be seen with one exception. The second acetyl
substitution acts on the 3-acetyl group, and also the parameters
of the 1-acetyl group differ from those of the 3-acetyl one. Inside
the ethyl groups a small decrease of the C–C distance and a small
increase of the N–C–C valence angle indicates the change from the
formyl to the acetyl group.
4.3. Vibrational force constants
The vibrational force constant matrices of the studied molecules
are very large. The molecules consist of 16 up to 27 atoms. There-
fore only selected diagonal force constants are presented in Table 5
together with the definition of the adjacent internal coordinates.
The definition of all internal coordinates and the values of the adja-
cent diagonal force constants are listed in Tables S2a, S2b and S2c.
The applied scale factors are listed in Table 6. Altogether 14 dif-
ferent scale factors are applied and the scale factors determined
for the indole molecule were transferred for the derivates in all
possible cases.
The diagonal force constants show also the influence of the sub-
stituent effects. Considering the environment of the nitrogen atom
the (diagonal) force constant of the N1–C2 bond increases with the
aldehyde substitution in position 3 (negative electron effect, −I,
−M). The alkyl substitution in position 1 (−I effect) affects against
and decreases a little bit the increased value. However, the acetyl
substitution in position 1 is nearer to N1 than the other in position
3 and therefore it acts stronger. The result is the decrease of this
force constant below the same of indole.
4.2. Atomic net charges
Atomic net charges were calculated applying the natural bond
orbital (NBO) analysis [30,31] and the Mulliken population analysis
[32].
Table 3 shows the atomic NBO charges. Looking at the sub-
stituent effect of the N1 atom, it is clear that its charge depends on
the neighboring substituent. Acetyl substitution shifts the charge
to positive direction, alkyl substituents, too, but latter ones show a
stronger effect. The net charges of atoms C3, C4, C5 and C6 depend
whether C3 is substituted or not, with one exception, they show
the strong electron effect of 1-acetyl substituent. The atoms C7 and
C8 can show only the chemical quality of the 1-substituent and can
distinguish three groups, hydrogen, alkyl group or acetyl group. As
it was expected, the atom C10 is sensitive only to the 1-substitution
and on the contrary, the atom C12 is only 3-substituent sensitive.
It is interesting that the net charge on H16 is influenced practically
only by the 1-acetyl substitution. The influence of the substitutions
on the net charges of all other hydrogen atoms is negligible.
The quality of the 3-substituent affects the net charge of the e2
atom of the 1-ethyl group, and also a small shift is observable on
those of the ethyl hydrogens. Comparing the charge distribution
in the 1-acetyl and 3-acetyl groups on the 1,3-diacetylindole, the
C–H bonds in the 1-acetyl group are more polarized than in the 3-
one, and the heavy atoms in the latter one are more negative, the
hydrogens are more positive than in the former.
The striking high value of the C8–C9 diagonal force constant
is the consequence of the choice of the internal coordinates. The
coordinates of the molecules were based on those of the phenol
ring. Therefore the five membered ring was regarded as consisting
of two substituents. This choice led a virtual tension on the C8–C9
bond. A similar but smaller effect is also seen on the values of the
C8–N1 constants.
Regarding the bond force constants of the six membered ring,
they show only minor substituent effects.
One can conclude that the changes of the aldehyde group in
position 3, and the changes of the alkyl group in position 1 act
remarkably on the charge distribution of the molecules. However,
the 1-acetyl substitution has the most significant effect, similarly
to its action on the geometric parameters.
For comparison, Mulliken’s atomic net charges are listed in
Table 4. Comparing the NBO charges and the Mulliken net charges,
the former ones express better the substituent effects. Although
here the values differ from the NBO ones, in several cases the ten-
The C12–Of1 formyl carbonyl stretch force constants some-
what decrease influenced by the 1-alkyl substitution. The similar
C12–Oa1 acetyl stretch force constants are somewhat smaller than
the formyl C O stretch ones but they are practically not influenced
by the 1-alkyl substitution. There is one exception, the C O stretch
force constant of the 1,3-diacetylindole. The electron effects of the
two acetyl groups increase mutually the electron densities on their
C
O bonds. This is reflected in the highest C O force constants
(C12-Oa1 and C10-Oc1) of all investigated molecules. Comparing

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1039
Table 6
Applied scale factors.
4.4.2. CH group vibrations
The effects on the CH stretch is more interesting. By investigat-
ing the six ␯CH vibrations of indole, they can be divided into two
groups according to their two rings. The two higher ones belong to
the pyrrole ring and are coupled to each other. The four lower ones
of the benzene ring are similarly coupled.
Internal coordinate type
In case
Scale factor
NH
o.o.p. deformation
Aldehydes
Formyl
3-Acetyl
1,3-Diacetyl
Aldehydes
All molecules, excluding formyl
Indole
Formyl
Formyl
Aldehydes
Skeleton
Acetyl
Alkyl
All molecules
Formyl
Aldehydes
All molecules, excluding formyl
Indole
All molecules
Ethyl
Alkyl
Indole
All molecules
Acetyl
Alkyl
0.844
0.865
0.875
0.905
0.914
0.923
C
C
C
O
O
O
Stretching
Stretching
Stretching
Substitution in position 3 leaves only one CH group in the
pyrrol ring. Of course, it has the highest frequency. The ␯C4–H13
vibration is decoupled from the other three ones of the aromatic
ring. The ␯C4–H13 vibration detected at the second highest fre-
quency among these vibrational modes. The other three benzene
␯CH modes are coupled and shift to lower frequencies. The aliphatic
CH stretch vibrations of the acetyl group are coupled. The ␯CH fre-
quency of the formyl group is very low, as it was expected. The
atom C4 of the benzene ring is in the vicinity of the formyl/acetyl
group and is affected by its negativ electron effect. Take a look at
the changes in the net charges of atoms C4 and H13 in Table 4. Both
show a larger positive shift in comparison with the other C and H
atoms of the benzene ring. The mentioned decoupling is observable
for all other studied indole derivatives as well.
The substitution of the NH hydrogen with methyl/ethyl groups
resulted in further changes of the CH stretch frequencies. The −I
effect of the N-methyl group causes also the decoupling of the
␯C7–H16 vibration from the other aromatic modes and this exhibits
the highest ␯CH frequency. The lower −I effect of the ethyl group
did not cause such a decoupling. All the three ␯CH vibrational
modes of the N-methyl group and the same of the 3-acetyl group
are coupled, respectively. It is interesting to mention that the N-
methyl and acetyl-methyl frequencies form pairs, between them
always the corresponding acetyl-methyl one has the highest fre-
quency (see Table 8). The corresponding diagonal force constants of
the acetyl-methyl CH stretching coordinates are between 490 and
500 N m−1, while the respective values for the N-methyl groups
are between 470 and 480 N m−1 (see deposited Table S2c). Simi-
larly, there are important differences between net charges of the
Ca2 and the C10 atoms of the mentioned molecules (see Table 4).
The effect of the N-ethyl substitution is similar to that of N-
methyl. The order of the (acetyl)methyl and the N-ethyl group
frequencies is variable.
NH
CH
NH
CH
CH
CC
CH
CH
CH
CC, NC
CH
CC
i.p. deformation
Stretching
Stretching
Torsion
i.p. deformation
o.o.p. deformation
o.o.p. deformation
Torsion
Torsion
Stretching
0.947
0.961
0.963
Stretching
i.p. deformation
i.p. deformation
i.p. deformation
i.p. deformation
i.p. deformation
i.p. deformation
o.o.p. deformation
Torsion
CH
NH
Ring
CC
0.966
NC
NH
Ring
CC
0.986
0.995
Torsion
CC
Torsion
NC
C
C
o.o.p. deformation
Torsion
i.p. deformation
All molecules
All molecules
All molecules
O
O
1.056
1.062
the C O bond lengths (Table 2) with their diagonal force con-
stants, a similar but antibate effect can be observed, e.g. indeed, the
shortest C O bond lengths can be found in the 1,3-diacetylindole
molecule.
4.4. Vibrational frequencies
Applying the scale factors (Table 6), the measured and calcu-
lated normal frequencies are very close to each other. Their main
deviations for the eight molecules are about 1% with the excep-
tion of 3-acetylindole, that is 1.5%. Table 7 compares the previously
recorded and calculated fundamental frequencies with our results.
The table comprises both experimental and calculated frequencies.
The quantum chemically calculated ones are either scaled or not
scaled. The scaling is mostly (in the literature) based on the vapour
phase experimental spectra. The value of the NH stretch frequency,
higher than 3500 cm−1, is a good indicator. The smaller part of the
scaled results, like ours, are based on the condensed phase indole
spectra and so their NH stretch frequencies are lower, a little over
3400 cm−1. We chose this solution because our indole derivatives
are solid crystalline compounds and we wished to transfer the scale
factors of indole to its derivatives. The value of the unscaled fre-
quencies depends on the applied quantum chemical method (and
functional) and basis set.
The two acetyl groups affect the CH group vibrations of the ben-
zene ring the same way as the 1-ethyl and 3-formyl groups. The
CH stretch vibrations of both acetyl groups are coupled, however,
they appear altered, and the N-acetyl CH stretch vibrations always
appear at somewhat higher frequencies.
4.4.3. C O group vibrations
According to the calculated potential energy distributions,
the participations of the C O stretchings in these vibrations are
between 70 and 75%. They are not pure C O stretch vibrations
but these coordinates are dominant in the discussed bands (see
Table 8).
Frequencies of the calculated formyl C O stretch vibrations are
deteted between 1642 and 1646 cm−1, the corresponding exper-
imental frequencies show alkyl substituent effect, i.e. the ethyl
group increases this frequency.
The group frequencies, their potential energy distributions
and other characteristic features are shown for all the studied
molecules/compounds in Table 8 . Tables S3–S10 (deposited) give
all the fundamental frequencies, their potential energy distribu-
tions and other characteristic features for our compounds table by
table.
The calculated acetyl C O stretch frequencies show a small
change between 1630 and 1634 cm−1 as an effect of the alkyl sub-
stitution. The experimental ones, however, increase stepwise with
the alkyl chain length from 1625.9 to 1642.6 cm−1
.
The introduction of the second acetyl group into the indole
molecule caused remarkable changes in the ␯C O region of the
spectrum. This fact is reflected in both the experimental and the
simulated spectrum. The frequency of the 3-acetyl ␯C O band
increased by about 20 cm−1 (at 1661.8 cm−1). The same band of
the N-acetyl group appeared at 1714.6 cm−1. The C O bond length
in the 3-acetyl group is 1.218 Å, while the same is 1.208 Å in the
4.4.1. NH group vibrations
The NH stretch frequencies are present only in indole and its
derivatives substituted only in position 3. As can be seen from data
in Table 8, the NH stretch frequencies are sensitive to this kind of
substitution, they shift to higher values.

1040
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
Table 7
Measured and calculated fundamental frequencies of indole (cm−1).
Ref. [5]
Ref. [6]
Ref. [8]
Ref. [9]
Ref. [11]
Measured
Vapour
Ref. [12]
Unscaled
Ref. [14]
Scaled
Ref. [15]
Unscaled
Ref. [16]
Scaled
This work
Measured
Measured
Scaled
AM1
Measured
Scaled
Scaled
HF 3-21G
Liquid
BLYP
B3LYP
B3LYP
B3LYP
B3LYP
6-31G*
6-31G**
6-31G**
6-311++G**
6-311G**
–
–
–
–
–
–
–
–
–
–
–
–
–
–
3520
3140
3083
3083
3068
3068
3068
1617
1578
1510
1489
1458
1410
1348
1300
1275
1245
1205
1150
1122
1082
1068
1015
968
930
900
869
860
800
762
761
738
715
625
608
575
544
428
400
400
3548
3523
3118
–
3072
3051
–
3523
3524
3420
3128
3106
3085
3059
3051
3041
1616
1578
1510
1488
1455
1412
1352
1334
1277
1246
1205
1149
1121
1093
1064
1011
965
930
895
878
860
848
766
760
741
723
609
606
575
544
424
398
485
3547
3525
3689.2
3273.7
3254.0
3204.0
3192.2
3181.6
3175.2
1674.9
1632.1
1567.5
1635.9
1494.8
1459.5
1391.8
1379.4
1308.2
1273.7
1227.5
1179.3
1147.8
1113.6
1094.8
1040.1
970.8
927.9
909.4
885.1
862.3
855.2
783.6
776.4
755.3
730.4
617.4
616.6
585.1
552.2
433.6
403.5
385.9
3539
3401.8
3127.8
3098.6
3085.9
3049.5
3041.7
3022.4
1615.4
1576.9
1505.4
1487.4
1455.5
1416.8
1353.8
1336.9
1277.7
1247.1
1205.4
1154.8
1119.5
1090.6
1060.4
1009.9
931.5
902.1
897.5
878.0
863.7
848.7
766.7
749.6
731.1
722.1
615.7
607.4
579.9
544.8
430.2
383.3
383.3
3404.5
3126.6
3106.5
3063.0
3051.5
3041.1
3034.9
1628.2
1586.5
1521.4
1496.6
1451.6
1417.9
1355.6
1336.5
1272.3
1243.3
1198.4
1151.7
1119.5
1087.5
1067.2
1012.6
941.9
905.3
894.0
870.6
839.4
832.4
774.6
760.1
731.0
709.2
615.4
607.3
584.9
542.1
429.4
396.4
383.4
3174
3118
3095
3087
3079
3071
1633
1571
1520
1472
1447
1423
1359
1315
1296
1245
1222
1187
1152
1108
1065
1042
935
922
893
865
892
828
797
780
782
760
620
613
560
553
437
413
256
3131
3107
3063
3051
3040
3032
1607
1573
1520
1493
1457
1403
1358
3140
3119
–
3194
3174
3122
3112
3102
3094
1613
1572
1514
1491
1450
1414
1357
1340
1269
1242
1192
1157
1119
1082
1065
1012
926
880
882
861
829
801
757
753
729
698
599
596
566
538
422
330
394
3147
3128
3080
3068
3058
3052
1625
1582
1519
1496
1457
1423
1356
1338
1275
1240
1198
1149
1120
1091
1067
1005
961
918
896
874
851
845
766
757
745
718
507
501
568
543
422
398
379
3135
3116
3071
3060
3050
3044
1595
1555
1488
1466
1423
1388
1329
1312
1246
1219
1175
1130
1098
1066
1046
993
938
902
876
853
835
821
749
745
721
697
595
591
561
531
415
388
3072
3058
3051
1625
1580
1519
1486
1458
1411
1347
1332
1276
1245
1205
1150
1121
1093
1067
1014
961
925
899
877
850
840
764
758
738
715
607
601
570
543
419
397
387
–
–
1616 1614
1576 1575
1509 1506
1487 1487
1455 1458
1412 1415
1352 1382
1334 1355
1276 1336
1245 1275
1203 1247
1161 1202
1147 1143
1119 1118
1092 1092
1064 1058
1010 1022
970
930
895
873
848
767
758
743
725
608
607
575
542
487
397
(397)
254
224
1576
1520
1479
1458
1414
1347
1330
1278
1244
1227
1204
1150
1122
1083
1067
1014
979
904
925
899
879
850
791
745
738
715
612
570
538
516
420
387
240
207
1276
1253
1228
1190
1156
1121
1090
1038
998
979
899
941
899
873
856
771
749
740
714
619
556
544
518
414
393
237
207
1008
945
898
875
862
768
752
730
612
580
505
498
425
395
–
–
–
–
365
233
204
240
208
231
224
241
207
256
227
236
206
240
211
246.0
216.7
261.5
231.4
243.9
212.5
N-acetyl group (Table 2). It is interesting that the diagonal force
constants of both C O groups are higher than those of all other
studied molecules, the same of the 3-acetyl groups is the great-
est. This fact is a nice example for that the effective value of the
frequency also depends on the non-diagonal force constants (the
full F matrix) and on the geometric parameters of the molecule (G
matrix).
very strong intermolecular interactions on this band. The carbonyl
bands show only a small frequency shift to higher value with the
longer alkyl substitution. Thus, it can be concluded that the inter-
molecular interaction is mainly due to hydrogen bridge formation
between the NH groups.
Regarding the Raman spectra (Fig. 4), the NH stretch bands dis-
appeared practically. The CH stretch bands are weak, the carbonyl
bands are relatively strong and show the aforementioned shift.
Figs. 5 and 6 show the substituent effect on the infrared and
Raman spectra of the investigated acetyl derivatives of indole,
respectively. The spectra of the methyl derivative are similar to the
ethyl ones. They are not presented for avoiding the packed figure.
The infrared spectra in Fig. 5. reflect the changes from formyl
to acetyl group. Comparing the infrared spectra of 3-acetyl- and
3-formylindols the first difference is the less extended NH stretch
bond. This refers to a weaker intermolecular interaction. The alkyl
substitution exhibits weaker effect on the acetyl group than on
the formyl one. The shift of the C O stretch band is smaller here
(see Table 8). Of course, the second acetyl group act strong on the
molecule as it was also discussed in the previous sections. The
shape of the spectrum rearranged in order to compare the spectra
of the 1-methyl-3-acetyl compound with that of the 1,3-diacetyl
derivative.
4.5. Experimental and simulated spectra
As it was already mentioned, experimental (infrared and
Raman) spectra of every studied compound was recorded. Simi-
larly, infrared and Raman spectra of all investigated molecules were
simulated based on the quantum chemical results and the scaling.
Figs. 3 and 4 present the substituent effect of infrared and Raman
spectra of the formyl derivatives compared to the parent com-
pound, respectively.
The infrared spectra of the formyl derivatives show the charac-
teristic vibrations more unambiguously than the Raman ones (see
also Table 8). The CH stretch bands overlap and are weak. Addition-
ally, the formyl CH stretch bands appear separately but they are also
very weak. The NH stretch band is separated well in indole, how-
ever, the spectrum of the 3-formyl derivative shows the effect of

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1041
Fig. 3. Substituent effect on the measured infrared spectra of the formylindols.
In the Raman spectra of the acetyl derivatives, the NH bands
are practically deminished. The CH stretch bands are stronger and
the bands of the individual CH groups are well distinguishable.
It is interesting that the band of the more polar carbonyl group
(connecting to the nitrogen atom, see Table 4) is less intense
than that of the other one. This band appears at even higher fre-
quency.
Figs. 3–6 introduced above show all the alkyl 1-substituent
effects. Fig. 7 deals with the 3-substituent effect. In this figure we
chose the measured and simulated infrared spectra of the studied
Table 8
Stretching vibrational modes of indole and its studied derivatives.

1042
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
Table 8
Table 8 (Continued )
1-ethylindoles. In the region below 1600 cm−1 the relative intensi-
ties are different. The intensity of the C O stretch band is both in the
measured and in the simulated spectra of the formyl derivative the
most intense, while in the spectrum of the acetyl derivative there
are several bands with commensurable intensity. While the formyl
CH stretch band is in the measured spectrum of low intensity, the
simulated spectrum overestimates its intensity as a result of the
applied model in the quantum chemical intensity calculations.
Fig. 4. Substituent effect on the measured Raman spectra of the formylindols.

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1043
Fig. 5. Measured infrared spectra of the investigated acetyl derivatives of indole.
Fig.
8
presents all the possible vibrational spectra of 3-
solid state. The measured NH stretch band is very broad, while
the calculated one is narrow. The calculated NH stretch band is
located at 3465 cm−1, while the maximum of the experimental one
is detected at 3160 cm−1. The source of the difference lies in the
transfer of the indole scale factors (including also the NH stretch
factor) to other derivatives, containing NH groups. The degree of
association in indole crystal is substantially lower than in the 3-
formyl- and 3-actylindole crystals (see also Fig. 5). The comparison
acetylindole. Comparing the measured infrared and Raman spectra
the very intense NH stretch band in infrared and the practically
disappeared one in Raman spectrum indicates the difference in the
mechanism of the two methods. The strong C O stretch band in
both spectra is surprising. Looking at the difference between the
measured and calculated spectra, the positions of the NH stretch
bands reflect well the effect of the intermolecular association in
Fig. 6. Measured Raman spectra of the investigated acetyl derivatives.

1044
F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
Fig. 7. The 3-substituent effect on the example of the infrared spectra of the 1-ethyl derivatives.
Fig. 8. Measured and calculated vibrational spectra of 3-acetylindole.

F. Billes et al. / Spectrochimica Acta Part A 74 (2009) 1031–1045
1045
of the measured and calculated Raman spectra reflects the weak
parts of the Raman intensity model, based on the partial derivatives
of the polarization matrix components to the Cartesian coordinates
of the atoms. The CH stretch band intensities are overestimated in
comparison to intensities of the other bands. Besides, the relative
intensities of the other bands are not commensurable with those
of the experimental bands either.
[2] L. Taiz, E. Zeiger, Plant Physiology, 2nd edition, Sinauer Associates, Inc., Mas-
sachusetts, 1998.
[3] www.chemistry.sogang.ac.kr/lecture/db/021-429/file/indole-1.doc.
[4] F. Millich, E.I. Becker, J. Org. Chem. 23 (1958) 1096.
[5] A. Lautié, M.F. Lautié, A. Gruger, S.A. Fakhri, Spectrochim. Acta A 36 (1980) 85
(in French).
[6] A. Suwaiyan, R. Zwarich, Spectrochim. Acta A 42 (1986) 1017.
[7] H. Takeuchi, I. Harada, Spectrochim. Acta A 42 (1986) 1069.
[8] W.B. Collier, J. Chem. Phys. 88 (1988) 7295.
[9] M. Majoube, C. Vergoten, J. Raman Spectrosc. 23 (1992) 431.
[10] T.L.O. Barstis, L.I. Grace, T.M. Dum, D.M. Lubman, J. Phys. Chem. 97 (1993) 5820.
[11] T.D. Klots, W.B. Collier, Spectrochim. Acta A 51 (1995) 1291.
[12] S.E. Walden, R.A. Wheeler, J. Chem. Soc. Perkin Trans. 2 (1996) 2653.
[13] W.B. Collier, I. Magdó, T.D. Klots, J. Chem. Phys. 110 (1999) 5710.
[14] A.A. El-Azhary, Spectrochim. Acta A 55 (1999) 2437.
5. Conclusions
The substitution of indole in position
3 with aldehydes
and with alkyl groups affect all properties of the studied
molecule/compound. These substitutions cause only small changes
in the molecular geometry, but substantially larger ones in the
charge distribution and in the vibrational force constants. The
appearance of the aldhyde groups increased the degree of asso-
ciation as it was observable on the shape of infrared NH stretching
band and its shifts. The alkyl substitution shifts the aldehyde car-
bonyl stretch band frequencies to somewhat higher values.
The effect of the second acetyl group in position 1 is not com-
parable with those of the 1-alkyl groups. Although this effect is
observable in the molecular geometry but it is more pronounced
in the changes of the net charge distribution, the vibrational force
constants and the infrared spectra.
[15] Y. Xue, Y. Guo, X.-J. Xu, D.-Q. Xie, G.-S. Yan, Acta Chim. Sin. 58 (2000) 1254.
[16] N. Sundaraganesan, H. Umamaheswari, J.B. Dominic, C. Meganathan, M. Rama-
lingam, J. Mol. Struct.-THEOCHEM 850 (2008) 84.
[17] C. Unterberg, A. Jansen, M. Gerhads, J. Chem. Phys. 113 (2000) 7945.
[18] A.F. Jalbout, C.S. Hall, L. Adamowicz, J. Chem. Phys. 118 (2003) 10541.
[19] X. Zhou, R. Liu, J. Mol. Struct.-THEOCHEM 461–462 (1999) 569.
[20] M. Yourtsever, E. Yurtsever, Polymer 43 (2002) 6019.
[21] B.J. Smith, R. Liu, J. Mol. Struct.-THEOCHEM 491 (1999) 211.
[22] T.L.O. Barstis, L.I. Grace, T.M. Dum, M.D. Lubman, J. Phys. Chem. 9 (1994) 4261.
[23] V. Arjunan, N. Puviarasan, S. Mohan, Spectrochim. Acta A 64 (2006) 233.
[24] J.R. Carney, T.S. Zwier, J. Phys. Chem. A 103 (1999) 9943.
[25] A. Suwayan, M.A. Morsy, Spectrochim. Acta A 53 (1997) 575.
[26] B. Morzyk-Ociepa, D. Michalska, A. Pietraszko, J. Mol. Struct. 688 (2004) 79.
[27] O. Ottoni, A. de Neder, A.K. Dias, R. Cruz, B. Aquinol, Org. Lett. 3 (2001) 1005.
[28] J. Varga, J. Lejtovicz, PCCP Software, Chemical Reseach Center, Hungarian
Academy of Sciences, Budapest, 1991.
[29] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson,
H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T.
Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian,
J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J.
Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A.
Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels,
M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman,
J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A.
Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. Al-Laham,
C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen,
M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03, Revision C.02, Gaussian, Inc.,
Wallingford, CT, 2004.
Acknowledgement
The authors are grateful to Dr Erzsébet Horváth for her help in
the Raman spectroscopic measurements.
Appendix A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.saa.2009.08.044.
[30] A.E. Reed, R.B. Weinstock, F.J. Weinhold, J. Chem. Phys. 83 (1985) 735.
[31] A.E. Reed, F.J. Weinhold, L.A. Curtiss, Chem. Rev. 88 (1988) 899.
[32] R.S. Mulliken, J. Chem. Phys. 23 (1955) 1833.
References
[1] J.V. Hidgon, B.W. Delage, R.H. Dashwood, Pharmacol. Res. 55 (3) (2007) 224.