Acid-base properties, FT-IR, FT-Raman spectroscopy and computational study of 1-(pyrid-4-yl)piperazine

Article abstract of DOI:10.1016/j.saa.2013.10.119

We report the vibrational spectral analysis was carried out using FT-IR and FT-Raman spectroscopy for 1-(pyrid-4-yl)piperazine (PyPi). Single crystals of PyPi suitable for X-ray structural analysis were obtained. The acid-base properties are also reported. PyPi supported on a weak acid cation-exchanger in the single protonated form and this system can be used efficiently as the solid supported analogue of 4-N,N-dimethyl-aminopyridine. The complete vibrational assignments of wavenumbers were made on the basis of potential energy distribution. The HOMO and LUMO analysis is used to determine the charge transfer within the molecule and with the molecular electrostatic potential map was applied for the reactivity assessment of PyPi molecule toward proton, electrophiles and nucleopholes as well. The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has been analyzed using NBO analysis. The calculated first hyperpolarizability of PyPi is 17.46 times that of urea.

Full text of DOI:10.1016/j.saa.2013.10.119

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
Contents lists available at ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
Acid–base properties, FT-IR, FT-Raman spectroscopy and computational
study of 1-(pyrid-4-yl)piperazine
a
c
Y. Sheena Mary a, C. Yohannan Panicker b, , Hema Tresa Varghese , Christian Van Alsenoy ,
⇑
d
d
d
ˇ
Markéta Procházková , Richard Ševcík , Pavel Pazdera
a Department of Physics, Fatima Mata National College, Kollam, Kerala, India
b Department of Physics, TKM College of Arts and Science, Kollam, Kerala, India
c Department of Chemistry, University of Antwerp, B2610 Antwerp, Belgium
d Centre for Syntheses at Sustainable Conditions and Their Management, Faculty of Science, Masaryk University, Brno, Czech Republic
h i g h l i g h t s
g r a p h i c a l a b s t r a c t
ꢀ
ꢀ
IR, Raman spectra and acid–base
properties are reported.
The wavenumbers are calculated
theoretically using Gaussian09
software.
ꢀ
ꢀ
The geometrical parameters are in
agreement with the XRD data.
Application of FMO, MEP and PED
analyses of PyPi.
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 31 August 2013
Received in revised form 22 October 2013
Accepted 31 October 2013
Available online 9 November 2013
We report the vibrational spectral analysis was carried out using FT-IR and FT-Raman spectroscopy for
1-(pyrid-4-yl)piperazine (PyPi). Single crystals of PyPi suitable for X-ray structural analysis were
obtained. The acid–base properties are also reported. PyPi supported on a weak acid cation-exchanger
in the single protonated form and this system can be used efficiently as the solid supported analogue
of 4-N,N-dimethyl-aminopyridine. The complete vibrational assignments of wavenumbers were made
on the basis of potential energy distribution. The HOMO and LUMO analysis is used to determine the
charge transfer within the molecule and with the molecular electrostatic potential map was applied
for the reactivity assessment of PyPi molecule toward proton, electrophiles and nucleopholes as well.
The stability of the molecule arising from hyper-conjugative interaction and charge delocalization has
been analyzed using NBO analysis. The calculated first hyperpolarizability of PyPi is 17.46 times that
of urea.
Keywords:
Piperazine
DFT
PED
FT-IR
FT-Raman
Ó 2013 Elsevier B.V. All rights reserved.
Introduction
their chemical similarity with piperadine, a constituent of piperine
in the black pepper plant. Piperazine owes its anthelmintic activity
Piperazine is a potent anthelmintic used in the therapy of
ascariasis (roundworms) and oxyuriasis (threadworms/pinworms)
infestations. The piperazaines were originally named because of
to its ability to produce flaccid paralysis of the muscles of the
parasite [1]. Piperazines have been reported in gene transfer
reactions [2] and quaternary piperazinium salts have shown
spasmolytic, anthelmintic and germicidal activity. Some piperazine
derivatives possess high biological activity for multidrug resistance
in cancer and malaria [3]. Gunasekaran and Anita [4] reported the
⇑
Corresponding author. Tel.: +91 9895370968.
E-mail address: cyphyp@rediffmail.com (C.Y. Panicker).
1386-1425/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2013.10.119

Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
437
spectral investigation and normal coordinate analysis of pipera
zine. Panicker et al. reported the spectroscopic investigations of
1-benzylpiperazine [5]. Kesan et al. [6] reported the FT-IR and
Raman spectroscopic and quantum chemical investigations of
some halide complexes of 1-phenylpiperazine. 1-(Pyrid-4-yl)piper-
azine (PyPi) belongs to a group 4-N,N-dialkylanalogues of 4-N,N-
dimethyl-aminopyridine (DMAP). DMAP and its analogues, for
example 4-pyrrolidinopyridine (PPy), are recently useful as
catalysts in laboratory and in technological processes, as well. First
of all like activators of electrophilic reagents, particularly like
activators of acylation reagents in production of chemical and
pharmaceutical specialties. DMAP analogues can be used like
nucleophilic catalysts for the Morita–Baylis–Hillman reaction.
Examples of their using are written in summary publications [7–
10]. PyPi is moreover mainly pharmaceutical intermediate in phar-
maceutical production. Its structural motive appears in chemical
structure of a lot of pharmaceutics or in chemical structure of
potential pharmaceutics from group of substituted di-sulfona-
mides. These pharmaceutics are widely used for softening of pain
or for suppressing of pain, which is evoked from bradykinin
receptors 1 [11]. Structural motive of PyPi also appears in chemical
structure of CXC-chemokine receptor ligands and in chemical
structure of 3,4-disubstituted cyclobuten-1,2-diones [12]. These
pharmaceuticals are used for treatment for prophylaxis or for
treatment for various diseases evoked abnormal production TNF-
a
and diseases treatable by IL-10 like as acute and chronic inflam-
matory diseases, allergic and autoimmune diseases [13]. Other
type of pharmaceutics containing structural motive of Pypi are
2,3-dihydro-3-[4-(substituted)piperazinyl]-1H-isoindole-1-ones
which are used for treatment of hypertension [14], also CCR5
antagonists which are used for treatment of HIV-1 [15], hybrid
and isosteric analogues of 1-acetyl-4-dimethylpiperazinium iodide
(ADMP) and 1-fenyl-4-dimethylpiperazinium iodide (DMPP).
These pharmaceutics are effective for central nicotinic acetylcho-
line receptors (nAChRs), which plays main role in neurodegenera-
tive diseases, for example Parkinson and Alzheimer disease [16].
Fig. 1. FT-IR spectrum of 1-(pyrid-4-yl)piperazine.
Structural motive of PyPi also appears in
l-opioid receptors
(MOR) antagonists [17], in indol compositions for treatment of
nephritis [18], in piperazine structural compositions which are
used for dissolving of blood clots during heart or brain strokes
[19] and in 4-arylpiperazines with positive allosteric modulation
of metabotropic glutamate receptors 5 (mGluR5) which are used
for treatment of schizophrenic patients [20]. Structural motive of
1-(pyrid-4-yl)piperazine is instead of a lot of its applications in
pharmaceutical chemistry main component of ligands which are
used in homogeneous catalysis to production of supra-molecular
complexes [21]. In the present work, the vibrational spectroscopic
studies and acid–base properties of the title compound are
reported.
Cambridge Crystallographic Data Center as supplementary
publications number CCDC 836336.
The FT-IR spectrum (Fig. 1) of PyPi was recorded using a Genesis
(Unicam Mattson) spectrometer-solid in Nujol. The FT-Raman
spectrum (Fig. 2) was obtained on a Bruker, Equinox 55/s spec-
trometer with FRA Raman socket, 106/s. For a excitation of the
spectrum the emission of the Nd:YAG laser was used, excitation
wavelength 1064 nm, maximal power 500 mV, measurement on
solid sample.
1-(Pyrid-4-yl)piperazine was prepared from 4-(pyridinium-4-
yl)piperazin-1-ium dichloride, purchased from Acros Organics
(Belgium), by neutralization with 2 equivalent of sodium hydrox-
ide in methanol. Sodium chloride was filtered of, methanol was
evaporated and solid white substance was recrystallized from
n-heptane. M.p. 139.5–140 °C, literature [25] 140 °C (heptane).
1H NMR spectrum (300 MHz, CDCl3) d/ppm: 8.10–8.08 (2H, m,
Py-H), 6.52–6.50 (2H, m, Py-H), 3.15–3.12 (4H, m, CH2), 2.85–2.82
(4H, m, CH2), 2.69 (NH). Purity controlled by GC was 99.1%.
Experimental
Potentiometric titrations were done by using instrument
Titroline alpha plus (SCHOTT, Fischer Scientific) and electrode
SenTix 21 (WTW). The fraction diagram of all three forms of Pypi
in dependence on pH was calculated by using Hydra/Medusa
Chemical Equilibrium Database and Plotting Software [22]. X-ray
crystal data and structure refinement of PyPi were collected with
a KUMA KM-4 kappa four-circle diffractometer. The structure
was solved by direct methods using SHELXS86 [23] and refined
on F2 for all reflections using SHELX193 [24]. Single crystals of PyPi
suitable for X-ray structural analysis was obtained in the form of
white prisms by crystallization from n-heptane at room tempera-
ture. The PyPi crystallographic data have been deposited with the
Acid–base properties
Acid–base constants of 1-(pyrid-4-yl)piperazine were deter-
mined by using of potentiometric titrations. Titrations of PyPi (con-
centration 0.01 M) as a free base form and re-titrations of PyPi in a
conjugated bis-protonated form PyPiꢁ2HCl, i.e. 4-(pyridinium-4-
yl)piperazin-1-ium dichloride (concentration 0.01 M), were done.
Potentiometric titrations of three standards, i.e. piperazine,
pyridine and DMAP in a free base form and their re-titrations in

438
Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
Fig. 4. Fraction diagram.
determined from titration curves after their fitting and differentiat-
ing. Scheme of PyPi protonation/deprotonation equilibria is
presented in Fig. 3 and obtained results of acid–base constants
for PyPi and for all three standards mentioned above are described
as pK values in the Table 1. The obtained pKa values of PyPi were
used for calculation offraction diagram (Fig. 4) of PyPi–PyPiꢁH+–
PyPiꢁ2H+.
Computational details
The vibrational wavenumbers were calculated using the
Gaussian09 software package on a personal computer [26]. The
computations were performed at HF/6-31Gꢂ, B3PW91/6-31Gꢂ and
B3LYP/6-31Gꢂ levels of theory to get the optimized geometry
(Fig. 5) and vibrational wavenumbers of the normal modes of the
title compound. DFT calculations were carried out with Becke’s
three-parameter hybrid model using the Lee–Yang–Parr correla-
tion functional (B3LYP) method. Molecular geometries were fully
optimized by Berny’s optimization algorithm using redundant
internal coordinates. Harmonic vibrational wavenumbers were cal-
culated using analytic second derivatives toconfirm the conver-
gence to minima in the potential surface. The DFT hybrid B3LYP
functional tends also to overestimate the fundamental modes;
therefore scaling factors have to be used for obtaining a consider-
ably better agreement with experimental data. Thus, a scaling
factor of 0.9613 has been uniformly applied to the B3LYP
calculated wavenumbers [27]. The observed disagreement
Fig. 2. FT-Raman spectrum of 1-(pyrid-4-yl)piperazine.
Fig. 3. Scheme of 1-(pyrid-4-yl)piperazine protonation/deprotonation equilibria.
Table 1
Observed pK values of studied amines.
Compound
pKa1
pKa2
pKb2
pKb1
1-(Pyrid-4-yl)piperazine 8.99 0.03 7.12 0.04 5.01 0.03 6.88 0.04
Piperazine
Pyridine
DMAP
9.61 0.04 5.40 0.05 4.39 0.04 8.60 0.05
5.25 0.02
8.36 0.03
–
–
–
–
8.75 0.02
5.64 0.03
a conjugated acid form were provided, as well. All potentiometric
titrations were realized in aqueous environment under tempera-
ture control (295 K) and potentiometric titration were repeated
for twelve times. Obtained data were statistically evaluated by
software Origin 8.1 and acid–base constants were graphically
Fig. 5. Optimized geometry (B3LYP) of 1-(pyrid-4-yl)piperazine.

Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
439
between theory and experiment could be a consequence of the
anharmonicity and of the general tendency of the quantum
chemical methods to overestimate the force constants at the exact
equilibrium geometry. Theobtained geometrical parameters are
given as supporting information in Table S1. Assignments of the
normal modes of vibration are done by Potential Energy Distribu-
tion calculation [28] and with the help of Gaussview software [29].
1230, 1209 cmꢃ1 in IR, 1380, 1289, 1228, 1204 cmꢃ1 in the Raman
spectrum and in the range 1192–1398 cmꢃ1 theoretically. The ban
ds calculated at 1096, 1047, 1044, 837 cmꢃ1 were assigned to the
rocking modes of CH2 [36]. The rocking modes are observed at
1107, 1052, 834 cmꢃ1 in the IR spectrum and at 1105, 832 cmꢃ1
in the Raman spectrum, as expected [36].
For 1-phenylpiperazine, the CH2 stretching vibrations have
been reported at 2944, 2910, 2881 and 2884 cmꢃ1 [37]. Krishnaku-
mar and Seshadri have reported the CH2 stretching modes of 2-
methylpiperazine at 3078 and 2532 cmꢃ1 [38]. The CH2 scissoring
vibrations of piperazine molecule were reported at 1455 and
1446 cmꢃ1 [39] while these modes are reported at 1452 cmꢃ1 for
1-phenylpiperazine [37] and at 1406 and 1293 cmꢃ1 for 2-methyl-
piperazine [38]. The CH2 scissoring vibrations observed for pipera-
zine and 1-phenylpiperazine are found to be consistent with the
results of the title compound. The piperazine ring stretching modes
are highly characteristic and in a study on the determination of
piperazine rings in ethyleneamines, poly(ethyleneamine) and
polyethylenimine by infrared spectroscopy, Spell reported that
the piperazine ring was found to be associated with sharp, well
Results and discussion
Acid–base properties
A comparison of the found both pK values of PyPi and pK values
for pyridine and piperazine, all given in Table 1, shows that a
protonation of neutral 1-(pyrid-4-yl)piperazine molecule starts
on the secondary nitrogen N of piperazine part and 4-(pyridin-4-
yl)piperazin-1-ium PyPiꢁH+ is formed. The tertiary pyridine
nitrogen atom in the cation PyPiꢁH+ is protonated consequently
at lower pH values. Hereinafter, this comparison shows the lower
basicity of secondary N3 in PyPi in the comparison with nitrogen
atom of electroneutral piperazine molecule. On the other hand,
the basicity of pyridine nitrogen in PyPiꢁH+ is higher than the one
in separate pyridine molecule, but, nevertheless lower than the
basicity of pyridine nitrogen in DMAP. The calculated fraction
diagram of the title compound (Fig. 4) displays that just PyPiꢁH+
cation is themajority form of PyPi in region pH values between 0
and 7 in water solutions and in protic solvents evidently, too. These
finding explain the facts that PyPi can be very effectively supported
on weak acid cation-exchanger in the single protonated form and
this system can be used efficiently as the solid supported analogue
of DMAP for activation of electrophiles in syntheses [30].
define absorptions at 1380–1345 cmꢃ1
,
1125–1170 cmꢃ1 and
1010–1025 cmꢃ1 regions of IR spectrum [40]. In accordance with
Spell [40], we have also observed a very strong peak in the IR spec-
trum at 1380 cmꢃ1 corresponding to CH2 wagging mode of the
piperazine ring. The theoretically calculated corresponding
wavenumber for the mode is 1379 cmꢃ1 with a PED of 81% and a
calculated IR intensity of 70.82. A very sharp and intense band
was observed at 1037 cmꢃ1 by da Silva et al. [41] and was assigned
to the ring CH2 rocking motions. As stated by Spell, [40] this is one
of the most useful bands for detecting the presence of di-substi-
tuted piperazines.ꢃ1In thepresent case, we have also observed a
band at 1052 cm
in the IR spectrum withcalculated values
1047 and 1044 cmꢃ1
.
IR and Raman spectra
For the title compound, the piperazine ring stretching modes
are observed at 1146, 1123, 1107, 853 cmꢃ1 in the IR spectrum
and at 1152, 1105 cmꢃ1 in the Raman spectrum. The calculated
values corresponding to these modes are 1131, 1130, 1096, 1034,
910 and 861 cmꢃ1. El-Emam et al. [42] reported the C–N stretching
vibrations of the piperazine ring in the region 1154–756 cmꢃ1. The
C–C stretching vibrations in the piperazine ring were reported at
972, 903 cmꢃ1 [42]. Two absorption characteristic for the pipera-
zine ring at 1130 and 1168 cmꢃ1 and assigned for the CN stretching
modes were observed by da Silva et al. [41]. In the present case, we
have observed bands in the IR spectrum at 1146 and 1123 cmꢃ1
corresponding to the piperazine ring stretching modes and the
shift in thewavenumber may be attributed to the bulky groups
attached to the piperazine ring. Piperazine ring modes are reported
at 1240, 1155, 1134, 1043, 1032, 1018, 1002, 974, 880 cmꢃ1 theo-
retically and at 1238, 1143, 1045, 1004, 874 cmꢃ1 experimentally
[43]. Gunasekaran and Anita reported the piperazine ring stretch-
ing modes at 1055, 1173, 1199, 1218, 1268, 1323 cmꢃ1 in the IR
spectrum and at 1049, 1120, 1186, 1294 cmꢃ1 inthe Raman spec-
trum [4].
The observed IR, Raman bands and calculated (scaled)
wavenumbers and assignments are given in Table 2. The N–H
stretching vibrations are generally give rise tobands [31,32] at
3500–3400 cmꢃ1. In the present study, the N–H stretching band
is split into a doublet 3383, 3223 cmꢃ1 in the IR spectrum owing
to Davydov coupling between neighboring units. A similar type
of splitting is reported Minitha et al. [33]. The splitting of about
160 cmꢃ1 in the IR spectrum is due to strong intermolecular hydro-
gen bonding. Further more the N–H stretching frequency is red
shifted by 144 cmꢃ1 in the IR spectrum with a strong intensity
from the computed frequency, which indicates the weakening
ofthe N–H bond resulting in proton transfer to the neighboring
units [34]. The NH deformation mode dNH is observed at
1428 cmꢃ1 in the IR spectrum, 1441 cmꢃ1 in the Raman spectrum
and at 1443 cmꢃ1 theoretically (B3LYP) as expected [35,36]. The
out-of-plane NH wag is expected in the region 725 25 cmꢃ1
[36] and in the present case the band at 782 cmꢃ1 (B3LYP) is
assigned as this mode.
In the vibrations of the CH2 group, the asymmetric stretching
The infrared spectrum of pyridine looks like that of mono-
substituted benzene and the spectrum of substituted pyridines
resemble those of substituted benzenes, counting the ring nitrogen
as a substituted carbon [36]. Vibrational assignments of the
pyridine ring are made by referring to the published studies on
selected organic structures [36], Colthup et al. [44], Silverstein
et al. [45], Urena et al. [46], Klots [47] and Panicker et al. [48].
The CH stretching vibrations of 4-substituted pyridines are usually
observed in therange 3010–3090 cmꢃ1 [47,49,50]. In the present
case, the bands observed at 3096 cmꢃ1 in the IR spectrum and at
3075 cmꢃ1 in the Raman spectrum corresponding CH modes. The
B3LYP calculations give these modes at 3109, 3098, 3043 and
t
asCH2, symmetric stretching
appears in the regions 3000 50, 2885 45 and 1440 25 cmꢃ1
respectively [35,36]. The B3LYP calculation gives asCH2 at 3031,
2999, 2970, 2969 cmꢃ1 and
sCH2 at 2879, 2871, 2835,
tsCH2, scissoring vibration dCH2
,
t
t
2829 cmꢃ1. The bands observed at 3034 cmꢃ1 in the IR spectrum
and at 3028, 2983, 2960, 2886, 2845, 2825 cmꢃ1 in the Raman
spectrum are assigned as CH2 stretching modes. The scissoring
modes dCH2 are assigned at 1474, 1463, 1460, 1452 cmꢃ1 theoret-
ically and corresponding to this mode, only one band is observed in
the IR spectrum at 1449 cmꢃ1. Absorption of hydrocarbons due to
CH2 twisting and wagging vibration [36] is observed in the region
1400–1150 cmꢃ1. These modes are assigned in 1404, 1380, 1292,
3039 cmꢃ1
.

440
Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
Table 2
Vibrational assignments of 1-(pyrid-4-yl)piperazine.
HF/6-31Gꢂ
B3PW91/6-31Gꢂ
B3LYP/6-31Gꢂ
IR
Raman
Assignments
t
IRI
RA
t
IRI
RA
t
IRI
RA
t
t
3368
–
0.80
–
9.38
161.78
–
3453
–
0.11
–
199.09
–
3367
–
1.19
–
198.86
–
3383
3223
–
3096
–
–
3034
–
–
–
–
–
3245
–
–
3075
–
–
3028
2983
–
2960
2886
–
2845
2825
1594
–
t
–
t
t
t
t
t
t
t
t
t
t
t
t
t
t
t
NH(100)
3051
3039
3002
2998
2962
2931
2905
2903
2834
2825
2809
2802
1614
1574
1504
1486
1479
1478
1466
1458
1423
1414
1398
1358
1345
1344
1333
1283
1248
1233
1215
1196
1154
1139
1115
1107
1084
1060
1058
1050
1029
1008
974
972
924
906
855
844
839
826
801
741
723
656
605
548
494
456
423
399
383
297
285
248
225
135
70
80.11
90.39
104.28
120.61
45.47
55.44
139.65
109.73
63.58
19.96
186.82
10.52
38.59
2.91
3127
3120
3085
3081
3055
3033
2991
2989
2900
2898
2835
2829
1594
1535
1497
1479
1471
1468
1462
1461
1420
1400
1391
1374
1350
1346
1331
1290
1285
1250
1244
1232
1208
1162
1144
1101
1098
1068
1054
1048
1045
974
968
955
937
922
863
842
826
807
728
720
667
664
582
533
479
459
436
388
382
314
272
254
210
138
10.39
22.49
31.62
31.07
13.97
16.31
43.69
41.72
108.33
12.89
105.64
46.11
345.72
35.53
92.74
3.03
38.59
0.31
5.03
12.20
6.45
40.93
13.86
8.69
122.83
88.01
102.38
138.73
39.13
39.89
164.73
131.60
178.15
23.86
191.47
30.28
39.35
0.29
4.34
11.83
9.43
21.53
8.03
7.70
3.85
12.97
1.56
8.40
1.67
4.00
5.55
28.19
13.79
5.75
4.00
6.03
21.60
2.02
0.50
0.47
1.38
13.51
0.77
6.79
3.51
4.05
38.50
2.09
10.09
0.30
3.73
0.79
4.40
0.26
3109
3098
3043
3039
3031
2999
2970
2969
2879
2871
2835
2829
1590
1539
1493
1474
1463
1460
1452
1443
1414
1398
1379
1355
1340
1334
1320
1280
1265
1234
1226
1221
1192
1131
1130
1096
1093
1063
1047
1044
1034
968
949
929
928
910
861
837
809
793
782
722
719
657
600
531
494
455
423
391
382
301
277
244
215
141
11.24
16.98
28.33
41.73
19.29
18.83
38.45
47.43
82.05
40.63
96.85
32.63
267.80
37.34
73.26
3.63
74.86
93.61
129.37
134.01
48.89
46.54
147.39
122.39
94.49
45.68
191.46
11.41
39.26
0.80
1.20
11.32
6.22
7.00
20.10
6.54
2.66
5.97
6.87
9.59
1.50
1.32
6.42
20.94
14.85
5.85
1.28
8.04
17.77
1.84
1.54
2.11
0.78
10.07
0.26
3.27
8.37
34.56
2.78
3.47
5.01
0.63
2.90
0.22
3.81
0.41
3.25
0.50
8.13
5.24
2.86
1.41
3.46
1.26
2.84
0.77
0.14
8.04
0.15
0.75
0.29
1.27
2.78
CH(97)
CH(95)
CH(95)
CH(98)
17.12
31.56
42.37
25.76
33.48
56.55
70.25
92.60
33.93
86.32
32.55
269.92
69.66
105.89
7.70
asCH2(94)
asCH2(96)
asCH2(97)
asCH2(98)
sCH2(91)
sCH2(90)
sCH2(96)
sCH2(96)
Py(59), dCH(22)
Py(66)
–
–
1603
1536
1496
–
–
–
1449
1428
–
1404
1380
–
–
1328
–
1292
1260
1245
1230
–
1209
1146
1123
1107
1087
1064
1052
–
–
–
949
–
924
–
853
834
808
–
–
737
–
637
606
539
472
442
419
–
–
–
–
–
–
–
–
–
2.91
12.28
0.82
–
–
–
–
Py(50), dCH(24)
dCH2(85)
dCH2(90)
dCH2(86)
dCH2(97)
dNH(61), dCH2(20)
dCH(52), tPy(22)
dCH2(61),
dCH2(61)
dCH2(29),
dCH2(74)
dCH(56), dCH2(12)
dCH2(53), dCH(17)
dCH2(71)
4.82
36.79
1.53
0.47
8.80
55.52
0.58
0.63
0.75
8.58
4.73
17.99
12.20
3.05
2.58
3.82
1.09
14.82
7.33
3.91
13.52
1.91
14.13
7.97
12.85
2.23
2.01
2.96
16.53
4.22
5.02
0.19
4.51
13.76
2.09
1.52
31.94
4.13
0.11
3.86
1.41
4.93
1.23
2.84
0.36
9.10
5.40
1.21
1.33
1.81
1.38
–
1441
–
–
1380
–
–
17.44
57.36
33.69
24.80
15.20
16.99
10.73
7.60
114.49
32.96
5.54
31.69
17.81
20.30
12.74
0.80
0.33
t
Pz(12)
70.82
18.33
16.58
4.73
36.03
13.25
1.33
129.16
20.33
20.32
4.56
t
C8N2(27)
4.88
3.65
1329
–
50.70
13.05
5.78
88.88
53.98
10.19
7.34
15.37
28.23
6.19
6.88
1.74
1.24
0.46
16.56
3.53
35.74
0.48
56.87
2.07
1.62
1.04
3.19
56.83
0.35
12.89
24.73
50.44
30.15
11.36
87.81
1.82
0.94
0.56
2.01
6.11
11.99
4.43
0.59
1.35
0.89
1289
1263
1243
1228
–
1204
1152
–
1105
1076
1065
–
–
–
988
947
–
–
–
–
832
–
–
–
736
–
661
–
t
Py(74)
dCH2(47),
dCH2(58),
dCH(68),
dCH2(90)
t
t
t
t
C8N2(17)
Py(14)
tPy(21)
9.50
Pz(58), dNH(19)
Pz(91)
36.55
22.05
8.81
0.16
1.14
15.51
4.75
33.42
0.16
27.60
22.50
3.11
14.81
3.64
10.77
40.29
71.32
3.08
9.45
0.51
9.08
9.28
34.89
0.91
1.23
dCH2(43), dPz(42)
dCH(48),
dCH(37),
dCH2(74)
t
t
Py(20)
Py(33), dPy(12)
0.65
1.05
11.57
9.59
0.26
dCH2(38), dPz(30)
t
t
c
c
c
t
t
Pz(60)
Py(52), dPy(20)
CH(92)
2.63
33.72
54.06
6.43
1.88
9.31
16.99
52.00
78.01
3.76
14.17
0.65
CH(51),
CH(56),
t
t
Pz(19)
Pz(18)
Pz(56)
Pz(60)
cCH(22)
dCH2(68)
c
c
c
CH(87)
CH(64),
NH(45),
c
t
C8N2(18),
Pz(28)
CH(14),
Pz(26), dC8N2(10)
sPy(14)
0.10
10.62
3.81
4.15
0.76
1.23
5.32
1.34
3.14
0.38
0.65
6.78
0.53
0.87
0.36
1.70
4.01
s
Py(68),
c
t
cC8N2(13),
dPy(27),
dPy(86)
8.55
dPy(28), dPz(23), dCH2(12)
C8N2(38), Py(38)
14.83
37.62
0.70
2.38
1.25
0.15
9.77
4.18
2.70
5.06
1.29
0.34
1.44
546
–
474
417
–
c
s
dPz(49), dPy(13),
dPz(72)
dC8N2(66)
cNH(11)
1.88
0.41
0.54
2.97
1.78
0.54
0.61
1.43
0.30
0.50
2.98
13.74
2.54
2.77
1.58
0.19
1.41
s
s
s
s
s
s
s
Pz(49),
Py(73)
Pz(32),
Pz(34),
Pz(78)
Pz(31),
Py(33), dC8N2(24),
C8N2(56), Pz(10)
CN(54), Pz(21)
s
Py(33)
–
326
286
–
–
–
s
c
Py(21)
C8N2(18),
C8N2(24),
s
Py(17)
Py(13)
c
s
sPz(24)
1.90
3.90
59
39
56
45
–
–
c
s
s
54
0.11
1.85
3.47
s
t
– Stretching; d – in-plane deformation;
c – out-of-plane deformation; s – twisting; Pz – pyrazine ring; Py – pyridine ring; as – asymmetric; s – symmetric; IRI – IR intensity;
RA – Raman activity; PED contribution is given in bracket in the assignment column.

Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
441
For 4-substituted pyridines, the ring stretching vibrations occur
in the general region 1600–1280 cmꢃ1 [36,45]. These modes
involve stretching and contraction of allthe bonds in the ring and
interaction between the stretching modes. For the title compound,
the pyridine ring stretching modes are assigned at 1603, 1536,
1496, 1260 cmꢃ1 in the IR spectrum and at 1594, 1263 cmꢃ1 in
the Raman spectrum. The B3LYP calculations give these modes in
the range 1265–1590 cmꢃ1. The ring stretching vibration is active
near 1335 35 cmꢃ1 a region which overlaps strongly with that
of the CH in-plane deformation and the intensity is in general
low [36,51]. Corresponding to this mode, the theoretical value is
1414 cmꢃ1 and no bands are observed experimentally. Thepyridine
ring breathing mode is expected in the range 1000 10 cmꢃ1 for
4-substituted pyridine [36,46] and in the present case the band
observed at 988 cmꢃ1 in the Raman spectrum is assigned as the
ring breathing mode.
In mono substituted pyridines, there should be four CH in-plane
bending modes and four out-of-plane bending modes and are
expected in the regions 1040–1330 and 780–990 cmꢃ1 respec-
tively [36,46]. For the title compound, the CH in-plane modes are
observed at 1328, 1087, 1064 cmꢃ1 in the IR spectrum, 1329,
1076, 1065 cmꢃ1 in theRaman spectrum and the out-of-plane CH
bending modes at 949, 924, 808 cmꢃ1 in the IR spectrum,
947 cmꢃ1 in the Raman spectrum. The B3LYP calculations give
the in-plane and out-of-plane CH modes in the range, 1063–1334
and 793–949 cmꢃ1 as expected [36,46]. The in-plane and out-of-
plane ring deformation modes of both rings and other substitutent
sensitive modes are also identified and assigned (Table 2).
donor (i) and acceptor (j) the stabilization energy (E2) associated
with thedelocalization i ? j is determined as
2
ðFi;jÞ
Eð2Þ ¼ Eij ¼ qi
D
ðEj ꢃ EiÞ
qi is the donor orbital occupancy, Ei, Ej the diagonal elements, and Fij
is the off diagonal NBO Fock matrix element.
In NBO analysis large E(2) value shows the intensive interaction
between electron-donors and electron-acceptors and greater the
extent of conjugation of the whole system, the possible intensive
interactions are given in Table 3. The second-order perturbation
theory analysis of Fock matrix in NBO basis shows intra molecular
hyper-conjugative interactions of p-electrons. The intra-molecular
hyper-conjugative interactions are formed by the orbital overlap
between n(N) and rꢂ(C–C) bond orbital which results in ICT
causing stabilization of the system. The intra-molecular hyper-
conjugative interaction of C9–C11 from of n1(N1) ? rꢂ(C9–C11
)
which increases ED (0.02505e) that weakens the respective bonds
leading to stabilization of 9.86 kcal molꢃ1
.
Also another intra-molecular hyper-conjugative interactions
are formed by theorbital overlap between n(N2) and pꢂ(C–C) bond
orbital of pyridine part which results in ICT causing stabilization of
the system. The strong intra-molecular hyper-conjugative interac-
tion of C8–C9 from of n1(N2) ? pꢂ(C8–C9) which increases ED
(0.40644e) thatweakens the respective bonds leading to stabiliza-
tion of 33.87 kcal molꢃ1. These interactions are observed as an
increase in electron density (ED) in C–C anti bonding orbital that
weakens the respective bonds. The increased electron density at
the nitrogen atoms leads to the elongation of respective bond
length and a lowering of the corresponding stretching wave
number. The electron density (ED) is transferred from then(N) to
NBO analysis
The natural bond orbitals (NBO) calculations were performed
using NBO 3.1 program [52] as implemented in the Gaussian 09
package at the DFT/B3LYP level in order to understand various
second-order interactions between the filled orbitals of one
subsystem and vacant orbitals of another subsystem, which is a
measure of the intermolecular delocalization or hyper-conjuga-
tion. NBO analysis provides the most accurate possible ‘natural Le-
wis structure’ picture of ‘j’ because all orbital details are
mathematically chosen to include the highest possible percentage
of the electron density. A useful aspect of the NBO method is that it
gives information about interactions of both filled and virtual
orbital spaces that could enhance the analysis of intra and inter
molecular interactions.
the anti-bonding rꢂ pꢂ orbital of the C–C explaining both the elon-
,
gation and the red shift [53]. The –C–N stretching modes can be
used as a good probe for evaluating thebonding configuration
around the corresponding atoms and the electronic distribution
ofthe molecule. Hence the above structure is stabilized by these
orbital interactions.
The NBO analysis also describes the bonding in terms of the
natural hybrid orbital n1(N2), which occupy a higher energy orbital
(ꢃ0.25538 a.u.) with considerable p-character (93.99%) and low
occupation number (1.76109 a.u) and the other n1(N1) occupy a
lower energy orbital (ꢃ0.32149 a.u) with p-character (69.77%)
and high occupation number (1.92497 a.u). Thus, a very close to
pure p-type lone pair orbital participates in the electron donation
to the pꢂ(C–C) orbital for n2(N2) ? pꢂ(C–C) interactions in the
compound. The results are tabulated as supporting information
in Table S2.
The second-order Fock-matrix was carried out to evaluate the
donor–acceptor interactions in the NBO basis. The interactions
result in a loss of occupancy from the localized NBO of the
idealized Lewis structure into an empty non-Lewis orbital. Foreach
Table 3
Second order perturbation theory analysis of Fock matrix in NBO basis corresponding to the intra-molecular bonds of the title compound.
Donor (i)
Type
ED/e
Acceptor (j)
Type
ED/e (kCal molꢃ1
)
E(2)a (a.u)
E(j)–E(i)b (a.u)
F(i,j)c
N1–C11
C4–C6
C4–C6
C6–C8
C8–C9
p
r
p
r
r
p
r
r
r
n
1.72616
1.98391
1.70658
1.97368
1.97417
1.62621
1.98377
1.98408
1.98325
1.92497
1.76109
1.92187
C4–C6
N2–C8
C8–C9
C8–C9
C6–C8
N1–C11
N2–C8
N2–C8
N2–C8
C9–C11
C8–C9
C16–H18
pꢂ
rꢂ
pꢂ
rꢂ
rꢂ
pꢂ
rꢂ
rꢂ
rꢂ
rꢂ
pꢂ
rꢂ
0.30332
0.03067
0.40644
0.02335
0.02287
0.39724
0.03067
0.03067
0.03067
0.02505
0.40644
0.03459
28.57
4.40
0.32
1.16
0.28
1.24
1.24
0.27
1.16
1.08
1.07
0.91
0.29
0.72
0.085
0.064
0.073
0.057
0.058
0.083
0.065
0.047
0.048
0.086
0.092
0.068
22.57
3.26
3.36
31.49
4.56
2.57
2.68
9.86
33.87
7.90
C8–C9
C13–C16
C13–C16
C19–C22
LP (1)N1
LP (1)N2
LP (1)N3
n
n
a
b
c
E(2) means energy of hyper-conjugative interactions (stabilization energy in kcal/mol.).
Energy difference (a.u.) between donor and acceptor i and j NBO orbitals.
F(i,j) is the Fock matrix elements (a.u.) between i and j NBO orbitals.

442
Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
where E0 is the energy of the unperturbed molecule, Fi is the field at
the origin, li ij, bijk and ijkl are the components of dipole moment,
Geometrical parameters and first hyperpolarizability
,
a
c
polarizability, the first hyperpolarizabilities, and second hyperpo-
larizabilities, respectively. The calculated first hyperpolarizability
of the title compound is 2.27 ꢅ 10ꢃ30 esu, which comparable with
the reported values of similar derivatives [61] and which is 17.46
times that of the standard NLO material urea(0.13 ꢅ 10ꢃ30 esu)
[62]. We conclude that the title compound is an attractive object
for future studies of nonlinear optical properties.
For the piperazine ring, El-Emam et al. [42] reported the bond
lengths N3–C16 = 1.465, N3–C19 = 1.463, C19–C22 = 1.514, N2–
C13 = 1.458, N2–C22 = 1.471, C16–C13 = 1.511 Å and the corre-
sponding bond lengths of the title compound are 1.461,
1.4605, 1.5297, 1.4696, 1.4638, 1.5275 Å (B3LYP) and 1.4585,
1.4455, 1.5068, 1.4574, 1.4734, 1.5075 Å(XRD), respectively. The
B3LYP calculations give the bond angles within the piperazine
ring N3–C19–C22 = 109.7, N3–C16–C13 = 109.0, N2–C13–C16 = 110.9,
N2–C22–C19 = 110.6, C13–N2–C22 = 112.8° and the corresponding
XRD values are 110.0°, 109.3°, 107.0°, 112.2° and 114.8°. El-
Emam et al. [42] reported the corresponding values as 110.0,
109.7, 109.7, 110.0 and 110.0° for different similar derivatives.
Molecular electrostatic potential
Molecular electrostatic potential (MEP) generally present in the
space around the molecule by the charge distribution is very useful
in understanding the sites of electrophilic attacks and nucleophilic
reaction for the study of biological recognition process [63] and
hydrogen bonding interactions [64]. In order to predict the molec-
ular reactive sites, the MEP for the title compound is calculated at
B3LYP method as shown in Fig. 6. The different values of the
electrostatic potential at the surface are represented by different
colors. Potential increases in the order red < orange < yel-
low < green < blue where blue indicates the highest electrostatic
potential energy and red indicates the lowest electrostatic poten-
tial energy. Intermediary colors represent intermediary electro-
static potentials. As it can be seen from the MEP map of the title
compound, the both nitrogen atoms N1 and N3 have the highest
value of electrostatic potential energy. This finding is in accordance
Karczmarzyk andMalinka [54] reported the dihedral angles C16
–
N3–C19–C22 = 61.1, C13–N2–C22–C19 = 60.1, N3–C19–C22
–
N2 = ꢃ61.5, C22–N2–C13–C16 = ꢃ58.2, C19–N3–C16–C13 = ꢃ58.9,
N2–C13–C16–N3 = 57.5°, which are in agreement with our calcu-
lated values, 61.8°, 52.7°, ꢃ56.3°, ꢃ53.2°, ꢃ61.9° and 56.8°. The
bond lengths C4–N1 = 1.3415(B3LYP), 1.3355(XRD) and C11–N1 -
= 1.3376(B3LYP), 1.3475(XRD), and C8–N2 = 1.3956(B3LYP),
1.3864 Å (XRD) are shorter than the normal C–N single bond
length of about 1.48 Å. The shortening of the CN bond lengths
reveal the effects of resonance in this part of the molecule [55].
All the carbon–carbon bond lengths in the pyridine ring lie in the
range 1.3887–1.4126 (B3LYP), 1.3735–1.4105 Å (XRD) and the CH
bond lengths in the range 1.083–1.0898 (B3LYP), 0.949–0.951 Å
(XRD). Here for the title compound, the pyridine ring is a regular
hexagon with bond length somewhere in between the normal val-
ues for a single (1.54 Å) and a double bond (1.33 Å) [56].
with
t he obtained results of acidobasic study of the title
compound. On the other hand, the lowest value of electrostatic
potential energy on N2 can be explained by conjugation of lone
The C–N bond lengths of piperazine ring are all close to the aver-
age single C–N bond length of 1.48 Å, being N2–C22 = 1.4638(B3LYP),
electron pair of N2 with pyridine conjugated
too see from the HOMO plot.
p-system. It can be
1.4734(XRD), N2–C13 = 1.4696 (B3LYP), 1.4574(XRD), N3–C16
-
= 1.4610(B3LYP), 1.4585(XRD) and N3–C19 = 1.4605 (B3LYP),
1.4455 Å (XRD). The C–N bond lengths in the pyridine ring C4-
N1 = 1.3415 (B3LYP), 1.3355 (XRD), C11-N1 = 1.3376(B3LYP),
1.3475 Å (XRD) are shorter than theother C–N bonds of the investi-
gated compound. This difference can be attributed to theelectro-
negativity effect of neighbor atoms and groups to these bonds. The
resonance effect between C and N atoms and Coulomb repulsive
interaction between CH2 groups give rise to the C–N bond lengths
(ꢄ1.46 Å) to be shorter than the C–C bonds lengths (ꢄ1.53 Å) in
the piperazine ring.
Nonlinear optics deals with the interaction of applied
electromagnetic fields invarious materials to generate new elec-
tromagnetic fields, altered in wavenumber, phase, or other phys-
ical properties [57]. Organic molecules able to manipulate
photonic signals efficiently are of importance in technologies such
as optical communication, optical computing, and dynamic image
processing [58,59]. In this context, the dynamic first hyperpolariz-
ability of the title compound is also calculated in the present
study. The first hyperpolarizability (b0) of this novel molecular
system is calculated using B3LYP method, based on the finite field
approach. In the presence of an applied electric field, the energy of
a system is a function of the electric field. First hyperpolarizability
is a third rank tensor that can be described by a 3 ꢅ 3 ꢅ 3 matrix.
The 27 components of the 3D matrix can be reduced to 10 com-
ponents due to the Kleinman symmetry [60]. The components of
b are defined as the coefficients in the Taylor series expansion
of the energy in the external electric field. When the electric field
is weak and homogeneous, this expansion becomes
HOMO–LUMO energy gap
The conjugated molecules are characterized by a highest occu-
pied molecular orbital-lowest unoccupied molecular orbital
(HOMO–LUMO) separation, which is the result of a significant de-
gree of ICT from the end-capping electron donor to the efficient
electron acceptor group through
charge transfer interaction through
in substantial ground state donor acceptor mixing and the appear-
ance of a charge transfer band in the electronic absorption spec-
trum. Therefore, an ED transfer occurs from the more aromatic
part of the p-conjugated system in the electron donor side to elec-
tron withdrawing part. The aromatic orbital components of the
p
-conjugated path. The strong
-conjugated bridge results
p
molecular orbitals are shown in Fig. 7. The HOMO–LUMO energy
X
X
X
X
1
2
1
6
1
24
E ¼ E0 ꢃ
þ . . .
l
iFi ꢃ
a
ijFiFj ꢃ
bijkFiFjFk ꢃ
c
ijklFiFjFkFl
i
ij
ijk
ijkl
Fig. 6. MEP of 1-(pyrid-4-yl)piperazine.

Y.S. Mary et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 121 (2014) 436–444
443
xcalculated first hyperpolarizability of the title compound is
2.27 ꢅ 10ꢃ30 esu, which comparable with the reported values of
similar derivatives and which is 17.46 times that of the standard
NLO material urea(0.13 ꢅ 10ꢃ30 esu). We conclude that the title
compound is an attractive object for future studies of nonlinear
optical properties.
Acknowledgement
The authors are thankful to University of Antwerp for access to
the university’s CalcUA Supercomputer Cluster and Ministry of the
Industry and Trade of the Czech Republic for support of Grant No.
2A-1TP/09.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.saa.2013.10.119.
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gap values are found at 3.672 eV and HOMO–LUMO energy gap
explains the eventual charge transfer interaction takes place with-
in the molecule, which are responsible for the molecular reactivity
of the biomedical compound of the title molecule [65]. As it can be
seen from the HOMO plot of PyPi, the highest electron population
is allocated on N1 of pyridine skeleton. This fact connected with
the highest value of electrostatic potential energy, discussed above,
shows the kinetic possibility of pyridine nitrogen N1 for binding
with electrophiles, e.g. acyl electrophiles, and its ability of an acyl
activation. The same HOMO plot demonstrates why the nitrogen
N3 is effective for the binding of a proton only, in the case of kinet-
ically controlled interactions, because of its lower electron popula-
tion. The LUMO plot of PyPi implies the possibility of attack of soft
nucleophiles on C4, C6, C9 and C10 respectively, in effect with the
same chance.
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Conclusion
In this work, the vibrational spectral analysis was carried out
using FT-IR and FT-Raman spectroscopy for 1-(pyrid-4-yl)pipera-
zine (PyPi). The computations were performed at HF/6-31Gꢂ,
B3PW91/6-31Gꢂ and B3LYP/6-31Gꢂ levels of theory to get the
optimized geometry and vibrational wavenumbers of the normal
modes of the title compound. The complete vibrational assign-
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ties are also reported. PyPi can be very effectively supported on
weak acid cation-exchanger in the single protonated form and this
system can be used efficiently as the solid supported analogue of
4-N,N-dimethyl-aminopyridine for activation of electrophiles in
syntheses. The HOMO and LUMO analysis is used to determine
the charge transfer within the molecule. The stability of the
molecule arising from hyper-conjugative interaction and charge
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