Synthesis, crystal structures and spectral characterization of imidazo[1,2-a]pyrimidin-2-yl-acetic acid and related analog with imidazo[2,1-b]thiazole ring

Article abstract of DOI:10.1016/j.molstruc.2016.03.055

Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (HIPM-2-ac) and its analog with imidazo[2,1-b]thiazole ring (HITZ-6-ac) were synthesized and structurally characterized by single-crystal X-ray diffraction corroborated with calculations of Hirshfeld surfaces, which provided detailed insight into intermolecular interactions constituting both crystals. The IR and Raman spectra of HIPM-2-ac and HITZ-6-ac were recorded and interpreted in details with the aid of Density Functional Theory (DFT) calculations and Potential Energy Distribution (PED) analysis of computed normal vibrations. Special attention was paid on hydroxyl and methylene groups involved in hydrogen bonds, which vibrations were monitored by H/D substitution. Recrystallization of parent compounds from deuterium oxide (D₂O) solutions resulted in deuteration of their carboxylic OH groups and almost complete deuteration of HIPM-2-ac methylene group. The latter phenomenon is clearly reflected in the vibrational spectra and confirmed by ¹H NMR experiments in solution.

Full text of DOI:10.1016/j.molstruc.2016.03.055

Journal of Molecular Structure 1117 (2016) 153e163
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Synthesis, crystal structures and spectral characterization of imidazo
[1,2-a]pyrimidin-2-yl-acetic acid and related analog with imidazo[2,1-
b]thiazole ring
a
a
a
b
ꢀ
Agnieszka Dylong , Waldemar Goldeman , Michał Sowa , Katarzyna Slepokura ,
a
a, *
_ _
Piotr Drozdzewski , Ewa Matczak-Jon
a
_
ꢀ
Department of Chemistry, Wrocław University of Technology, Wybrzeze Wyspianskiego 27, 50-370 Wrocław, Poland
b Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (HIPM-2-ac) and its analog with imidazo[2,1-b]thiazole ring
(HITZ-6-ac) were synthesized and structurally characterized by single-crystal X-ray diffraction corrob-
orated with calculations of Hirshfeld surfaces, which provided detailed insight into intermolecular in-
teractions constituting both crystals.
The IR and Raman spectra of HIPM-2-ac and HITZ-6-ac were recorded and interpreted in details with
the aid of Density Functional Theory (DFT) calculations and Potential Energy Distribution (PED) analysis
of computed normal vibrations. Special attention was paid on hydroxyl and methylene groups involved
in hydrogen bonds, which vibrations were monitored by H/D substitution. Recrystallization of parent
compounds from deuterium oxide (D2O) solutions resulted in deuteration of their carboxylic OH groups
and almost complete deuteration of HIPM-2-ac methylene group. The latter phenomenon is clearly re-
flected in the vibrational spectra and confirmed by 1H NMR experiments in solution.
© 2016 Elsevier B.V. All rights reserved.
Received 8 January 2016
Received in revised form
16 March 2016
Accepted 16 March 2016
Available online 19 March 2016
Keywords:
Imidazo[1,2-a]pyrimidine
Imidazo[2,1-b]thiazole
Single-crystal X-ray diffraction
Hirshfeld surface analysis
DFT calculations
Vibrational spectroscopy
1. Introduction
antiparasitic [8], antiviral [9] or anticancer [10] agents.
Pharmaceutical significance of the compounds containing fused
Synthetic heterocycles constitute a vast family of compounds
gaining substantial interest in the field of medicinal chemistry.
Their great pharmacological potential lies in structural similarity to
naturally occurring heterocycles such as purines or indoles, which
makes them capable of binding to multiple biological targets with
high affinity and providing pharmaceutical activities in diverse
cellular processes. Of significant interest are bicyclic systems con-
taining imidazole ring, which is a common motif encountered in
biologically active compounds produced by nature [1e5]. Among
them imidazo[1,2-a]pyridine (IP) is the most widely studied and
most frequently represented in marketed drug formulations [2].
Scientific interest is also related to synthesis and evaluation of
biological activities of the compounds containing imidazo[1,2-a]
pyrimidine (IPM) and imidazo[2,1-b]thiazole (ITZ) scaffolds.
Numerous members of IPM and ITZ families have been reported to
exhibit remarkable potential as anxiolytic [6], antimicrobial [7],
IP, IPM and ITZ heterocyclic rings and limited literature available
regarding their structural and physicochemical characterization are
two important factors that prompted us to initiate systematic
studies on imidazole-based bicyclic systems appended with acetic
group. Recently, we have demonstrated that imidazo[1,2-a]pyridin-
2-yl-acetic acid (HIP-2-ac) exists in the solid state as a zwitterion,
with a proton transferred from carboxylic group to imidazole N
atom and acts as a bifunctional N,O-donor ligand forming mostly
mononuclear complexes with d block metal ions [11,12]. In
continuation of our research interest in this class of compounds,
herein we report the synthesis, crystal structures and detailed
vibrational characterization of two structurally similar compounds,
namely, imidazo[1,2-a]pyrimidin-2-yl-acetic acid (HIPM-2-ac, 1)
and imidazo[2,1-b]thiazol-6-yl-acetic acid (HITZ-6-ac, 2) which has
been previously reported to be moderate anti-inflammatory agent
[13].
Single crystal X-ray diffraction studies have revealed that 1 and
2 crystallize as electrically neutral molecules, which is in contrast to
previously reported HIP-2-ac [11]. The structural descriptions have
* Corresponding author.
E-mail address: ewa.matczak-jon@pwr.edu.pl (E. Matczak-Jon).
http://dx.doi.org/10.1016/j.molstruc.2016.03.055
0022-2860/© 2016 Elsevier B.V. All rights reserved.

154
A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
additionally been corroborated with calculations of Hirshfeld sur-
faces, which provide detailed insight into intermolecular in-
teractions constituting crystals 1 and 2. Experimental IR and Raman
spectra of both compounds and their deuterated isotopologues 1a
and 2a have been interpreted in details with the aid of DFT calcu-
lations and PED analysis of computed normal vibrations. Moreover,
H/D substitution spectral effects have been used for respective
band assignments. As expected, typical three-fold recrystallization
of 2 from D2O/CD3OD solutions resulted in almost complete
deuteration of its carboxylic OH group. Surprisingly, in case of 1
both carboxylic and methylene groups have been found to be
deuterated. A rare phenomenon of H/D exchange in methylene
group of 1 has been revealed based on analysis of vibrational
spectra of 1 and 1a. A further support has been provided by 1H NMR
spectra of D2O solutions of 1 and 2 recorded as a function of time.
The spectra of 1 have demonstrated gradual decrease in intensity of
methylene group signal followed by its disappearance after c.a.
three days. In contrast, only insignificant spectral changes have
been observed under similar conditions for 2.
149.74 (C-7), 170.57 (COO) ppm.
The 1H and 13C NMR signal assignments were performed on the
basis of literature data [15,16].
Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (1) and imidazo[2,1-b]
thiazol-6-yl-acetic acid (2). To solution of the respective crude ethyl
ester (0.02 mol) in 100 ml of methanol 1.1 g (0.028 mol) of NaOH
was added, resulted mixture was refluxed for 4 h and cooled to
room temperature. 12 M hydrochloric acid was added dropwise
(~2.3 ml, 0.028 mol), the mixture was concentrated under reduced
pressure and the residue was treated with 30 ml of diethyl ether.
The solid was filtered by suction and washed with 15 ml portions of
diethyl ether (until the filtrates became colorless). The resulted
solid still containing sodium chloride was dried under reduced
pressure, dissolved in about 100 ml of boiling water, decolorized
with activated charcoal and concentrated to 25e30 ml. The solution
was left for 24 h at room temperature, the crystallized solid was
filtered by suction and washed with cold water (3 ꢀ 5 ml) and
acetone (2 ꢀ 25 ml). That gave 1.5 g (43%) of imidazo[1,2-a]pyr-
imidin-2-yl-acetic acid (1) as beige powder and 1.5 g (41%) of
imidazo[2,1-b]thiazol-6-yl-acetic acid (2) as the white tiny needles.
Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (1). 1H NMR (DMSO-d6,
2. Experimental
300 MHz):
d
¼ 3.73 (s, 2H, CH2), 7.00 (dd, J ¼ 4.1 Hz, J ¼ 6.7 Hz, 1H,
2.1. General information and materials
H-6), 7.80 (s, 1H, H-3), 8.46 (dd, J ¼ 4.1 Hz, J ¼ 2.0 Hz, 1H, H-7), 8.91
(dd, J ¼ 2.0 Hz, J ¼ 6.7 Hz, 1H, H-5), 12.43 (broad, 1H, COOH) ppm.
All reagents were obtained from commercial sources and used
without further purification.
13C NMR (DMSO-d6, 75 MHz):
d
¼ 35.35 (CH2), 108.93 (C-6), 110.11
(C-3), 135.50 (C-5), 141.74 (C-2), 147.53 (C-9), 149.89 (C-7), 172.32
(COOH) ppm. The 1H and 13C NMR signal assignments are consis-
tent with literature data [15,16]. (For more details see Figs. S1 and
S3); m.p. ¼ 205e206 ꢁC (H2O), literature m.p. ¼ 213e214 ꢁC
(EtOH) [17].
2.2. Syntheses of the compounds 1 and 2 and their precursors
Ethyl imidazo[2,1-b]thiazol-6-yl-acetate: in an 1000 ml round-
bottomed flask, a mixture of 45.0 g (0.215 mol) of the crude,
freshly prepared ethyl 4-bromoacetoacetate [14], 25.2 g (0.30 mol)
of the sodium bicarbonate and 20.0 g (0.20 mol) of 2-aminothiazole
in mixture of 400 ml 1,4-dioxane and 200 ml of anhydrous ethanol
was vigorously stirred for 16 h at room temperature and refluxed
for 8 h. The crude reaction mixture was evaporated to dryness and
400 ml of water was added. The water solution was extracted with
dichloromethane (2 ꢀ 150 ml) and the organic extracts were
washed with saturated solution of NaHCO3 (2 ꢀ 200 ml). The
organic layer was dried over anhydrous Na2SO4, filtered through a
plug of silica gel (30 g) and the filtrate was extracted with 1 M HClaq
(5 ꢀ 150 ml). The combined aqueous phases were neutralized with
solid sodium bicarbonate, extracted with dichloromethane
(2 ꢀ 150 ml), dried over anhydrous Na2SO4 and concentrated under
reduced pressure to afford a crude ethyl imidazo[2,1-b]thiazol-6-yl-
acetate (28.5 g, 68% yield) as a light brown thick liquid.
Imidazo[2,1-b]thiazol-6-yl-acetic acid (2). 1H NMR (DMSO-d6,
300 MHz):
1H, H-5), 7.83 (d, J ¼ 4.4 Hz, 1H, H-3), 12.36 (broad, 1H, COOH) ppm.
13C NMR (DMSO-d6, 75 MHz):
d
¼ 3.56 (s, 2H, CH2), 7.17 (d, J ¼ 4.4 Hz, 1H, H-2), 7.61 (s,
d
¼ 35.34 (CH2), 112.01 (C-5), 112.77
(C-2), 120.31 (C-3), 141.33 (C-6), 148.35 (C-8), 172.57 (COOH) ppm.
1H NMR spectrum is in agreement with the literature data [13] (for
more details see Figs. S2 and S4); m.p. ¼ 180e181 ꢁC (H2O), liter-
ature m.p. ¼ 185e187 ꢁC (EtOH) [13].
Compounds 1a and 2a were obtained by a recrystallization of 1
and 2 from D2O and CD3OD, respectively.
2.3. X-ray crystallography
Crystallographic measurements were performed on a Kuma
KM4-CCD automated four-circle diffractometer with graphite
monochromatized Mo Ka radiation at 100(2) K using an Oxford
1H NMR (CDCl3, 300 MHz):
d
¼ 1.26 (t, J ¼ 7.1 Hz, 3H, CH3), 3.72
(s, 2H, CH2), 4.16 (quartet, J ¼ 7.1 Hz, 2H, OCH2), 6.76 (d, J ¼ 4.6 Hz,
1H, H-2), 7.34 (d, J ¼ 4.6 Hz, 1H, H-3) 7.41 (s, 1H, H-5) ppm. 13C NMR
Cryosystems cooler. Data collection, cell refinement, data reduction
and analysis were carried out with CRYSALISCCD and CRYSALISRED,
respectively [18]. Multi-scan (for 1) and analytical (for 2) absorp-
tion correction was applied to the data with use of CRYSALISRED.
Both structures were solved with direct methods using SHELXS-
2014 [19a] and refined by a full-matrix least squares technique
with SHELXL-2014 [19b] with anisotropic thermal parameters for
all non-H atoms. All H-atoms were initially located in difference
Fourier maps, and in the final refinement cycles were treated as
described below. All C-bound H atoms were placed in calculated
positions, with CeH ¼ 0.95e0.99 Å, and refined with a riding model
with Uiso(H) ¼ 1.2Ueq(C). O-bound H atoms were allowed to refine
with OeH distance restrained to 0.840(2) Å and Uiso(H) ¼ 1.5Ueq(O),
and then they were constrained to ride on parent atoms (AFIX 3
instruction in SHELXL-2014). Crystallographic data and structure
refinement parameters are summarized in Table 1. All figures were
made using DIAMOND program [20].
(CDCl3, 75 MHz):
d
¼ 14.08 (s, CH3), 35.10 (CH2), 60.79 (OCH2),
110.81 (C-2), 111.92 (C-5), 118.54 (C-3), 140.66 (C-6), 149.08 (C-8),
170.80 (COO) ppm. The 1H and 13C NMR spectra are in agreement
with those described in the literature [13].
Ethyl imidazo[1,2-a]pyrimidin-2-yl-acetate was synthesized from
19.0 g (0.20 mol) of 2-aminopyrimidine by the procedure used for
ethyl imidazo[2,1-b]thiazol-6-yl-acetate (300 ml of anhydrous
ethanol was used as solvent). Ethyl imidazo[1,2-a]pyrimidin-2-yl-
acetate was obtained as brown thick oil (4.5 g, 11% yield), which
solidified upon standing at room temperature.
1H NMR (CDCl3, 300 MHz):
d
¼ 1.27 (t, J ¼ 7.2 Hz, 3H, CH3), 3.90
(s, 2H, CH2), 4.18 (quartet, J ¼ 7.2 Hz, 2H, OCH2), 6.82 (dd, J ¼ 6.7 Hz,
J ¼ 4.1 Hz, 1H, H-6), 7.58 (s, 1H, H-3), 8.38 (dd, J ¼ 6.7 Hz, J ¼ 2.1 Hz,
1H, H-5), 8.48 (dd, J ¼ 4.1 Hz, J ¼ 2.1 Hz, 1H, H-7) ppm. 13C NMR
(CDCl3, 75 MHz):
109.18 (C-6), 111.64 (C-3), 133.11 (C-5), 141.87 (C-2), 147.98 (C-9),
d
¼ 14.21 (s, CH3), 35.32 (CH2), 61.13 (OCH2),

A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
155
Table 1
Summary of crystallographic data and structure refinement results for 1 and 2.
2.6. Theoretical (DFT) calculations
The DFT calculations for 1 and 2 were performed employing the
GAUSSIAN 09 package [22]. The B3LYP functional [23] and LanL2DZ
basis set [24] were employed for providing a good comparison with
similar calculations to be carried out for metal complexes which we
are preparing with present and similar ligands. The calculations of
normal vibrations were performed on the optimized structures,
well corresponding to these determined by single-crystal X-ray
diffraction. Besides, the calculations for deuterated 1a and 2a iso-
topologues have also been performed. The potential energy distri-
bution (PED) terms were calculated by Fcart66 package [25].
Normal vibrations and corresponding IR and Raman bands were
characterized on the basis of PED results and additionally verified
by atom displacement animation done by Chemcraft program [26].
Calculation results were converted into theoretical spectra using
the Chemcraft application with Lorentzian band shape and 5 cmꢂ1
half band width. For easier comparison of observed and calculated
band positions the wavenumbers calculated above 2000 cm-1 were
scaled by 0.96 factor, typical for applied computation method [27].
Compound
1
2
CCDC No.
Formula
Formula weight
Crystal system
Space group
a (Å)
1436747
C8H7N3O2
177.17
orthorhombic
Pca21
19.255(6)
5.095(2)
7.572(3)
742.8(5)
4
1436748
C7H6N2O2S
182.20
orthorhombic
P212121
5.482(2)
7.449(3)
18.038(6)
736.6(5)
4
b (Å)
c (Å)
V (Å3)
Z
Crystal size (mm)
Temperature (K)
Radiation
Wavelength (Å)
0.36 ꢀ 0.25 ꢀ 0.10
0.40 ꢀ 0.24 ꢀ 0.06
100(2)
100(2)
Mo K
0.71073
0.12
1.584
368
3.4-28.7
5191
1705
1614
0.034
Empirical (multi-scan)
0.843/1.000
1705/118/2
0.034; 0.088
0.036; 0.089
1.10
a
Mo Ka
0.71073
0.39
1.643
376
3.0e28.6
5727
1799
1720
0.041
Analytical
0.859/0.976
1799/109/1
0.033; 0.087
0.035; 0.088
1.05
m
(mmꢂ1
)
dcalc (g$cmꢂ3
F(000)
)
q
range (ꢁ)
Reflections collected
Reflections independent
Reflections observed (I > 2
Rint
Absorptions correction
Tmin/Tmax
s(I))
3. Results and discussion
Data/parameters/restrains
3.1. Synthesis of 1, 2 and their precursors
R1; wR2 (F2o > 2 (Fo2))
s
R1; wR2 (all data)
GoF ¼ Sall
The synthesis of HIPM-2-ac (1) and HITZ-6-ac (2) is outlined in
Schemes 1 and 2, respectively. Both compounds were prepared by
alkaline hydrolysis of the appropriate ethyl esters following
neutralization of obtained salts. Thus, crude ethyl imidazo[1,2-a]
pyrimidin-2-yl-acetate and ethyl imidazo[2,1-b]thiazol-6-yl-ace-
tate were hydrolyzed to the sodium salt with sodium hydroxide in
boiling methanol and neutralized with stoichiometric amount of
hydrochloric acid to desired HIPM-2-ac and HITZ-6-ac.
Drmax
/
Drmin(eÅꢂ3
)
0.21/ꢂ0.23
0.33/ꢂ0.28
Absolute structure parameter
e
0.00(5)
2.4. Hirshfeld surface analysis
Hirshfeld surface maps and 2D fingerprint plots were prepared
using Crystal-Explorer v.3.0 [21] enabling quantitative estimation
of percentage contributions for various intermolecular contacts in
the reported crystals of 1 and 2.
Starting ethyl esters of above ligands were prepared by the
modification of the literature procedure, which is based on
condensation
of
ethyl
4-bromoacetoacetate
with
2-
aminopyrimidine [17,28] and 2-aminothiazole [13,29]. The same
modification was used previously for the synthesis of imidazo[1,2-
a]pyridin-2-yl-acetic acid (HIP-2-ac) and its ethyl ester [11]. Thus,
ethyl imidazo[1,2-a]pyrimidin-2-yl-acetate was obtained with 11%
yield by the condensation of crude ethyl 4-bromoacetoacetate
(prepared by bromination of the ethyl acetoacetate [14]) with 2-
aminopyrimidine in the presence of sodium bicarbonate in 1,4-
dioxane. Similar reaction with 2-aminothiazole in the 1,4-
dioxaneꢂethanol mixture gave ethyl imidazo[2,1-b]thiazol-6-yl-
acetate in 68% yield (Scheme 2).
2.5. Spectroscopy
Room-temperature 1D (1H, 13C NMR) spectra of 1 and 2 dis-
solved in DMSO-d6 were obtained using Bruker DRX 300 MHz
spectrometer operating at 300.13 and 75.46 MHz for 1H and 13C,
respectively. All remaining experiments were performed using
Bruker Avance™ 600 MHz spectrometer operating at 600.13 MHz
for 1H and 150.90 MHz for 13C. The standard Bruker program was
used to perform HSQC correlation experiments confirming spectral
assignments of 1 and 2. All experiments were performed with
locking spectrometer on deuterium from a solvent. Chemical shifts
are given in relation to TMS (SiMe4). All downfield shifts are
denoted as positive.
3.2. Solid state characterization of 1 and 2
Molecular structures and atom-numbering schemes for HIPM-2-
ac (1) and HITZ-6-ac (2) are shown in Fig. 1 whereas geometrical
parameters of hydrogen bonds are given in Table 2.
Infrared (ATR FT-IR) spectra were measured on a Bruker Vertex
70v Fourier transform infrared spectrometer equipped with a dia-
mond ATR cell. The spectral data were collected as 64 scans at room
temperature over the range 4000e400 cmꢂ1 and 600e40 cmꢂ1
with a resolution of 4 and 2 cmꢂ1, respectively.
Compounds 1 and 2 crystallize as electrically neutral molecules
in non-centrosymmetric Pca21 and P212121 space groups of the
orthorhombic crystal system, respectively. This is in contrast to
previously described HIP-2-ac [11], which crystallizes as a zwit-
terion with proton transferred from carboxylic group to imidazole
N atom. In both 1 and 2 the carboxylic group adopts the same
orientation with respect to the plane defined by the aromatic ring
and C10/C9 atoms. This is reflected in N1eC2eC10eC11 and
N7eC6eC9eC10 dihedral angles of 71.1(2) and ꢂ73.1(3)ꢁ,
respectively.
Raman spectra were collected on a Bruker MultiRam FT spec-
trometer equipped with a liquid nitrogen cooled germanium de-
tector and Nd:YAG laser with emitting radiation at a wavelength of
1064 nm. For each sample 128 scans were accumulated at laser
power equal 450 mW and with a resolution of 2 cmꢂ1
.
For IR and Raman measurements, the instrument control and
initial data processing were performed using OPUS software (v. 7.0
Bruker Optics, Ettlingen, Germany).
Crystal structures of 1 and 2 reveal presence of zigezag tape
motifs (Fig. S5) formed by hydrogen bonds between molecules
related by action of a 21 screw axis. In 1, those interactions comprise

156
A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
1) 1.4eq NaOH/MeOH
4h reflux
N
N
2) 1.4eq HClaq
N
OEt
N
N
OH
N
O
O
HIPM-2-ac
1) 1.4eq NaOH/MeOH
4h reflux
N
N
2) 1.4eq HClaq
S
N
OEt
S
N
OH
HITZ-6-ac
O
O
Scheme 1.
O
O
N
N
NaHCO3
Br
+
+
OEt
1,4-dioxane
N
OEt
OEt
N
NH2
N
11%
O
O
O
O
N
N
NaHCO3
Br
1,4-dioxane/EtOH
NH2
OEt
S
S
N
68%
Scheme 2. Synthesis of ethyl imidazo[1,2-a]pyrirmidin-2-yl-acetate and ethyl imidazo[2,1-b]thiazol-6-yl-acetate precursors of 1 and 2.
Table 2
Geometry of proposed hydrogen bonds and close CeH$$$O contacts in 1 and 2.
DdH$$$A
DdH
H$$$A
D$$$A
DdH$$$A
Compound 1
O2eH2$$$N1i
C3eH3$$$O1ii
C6eH6$$$O2iii
C7eH7$$$O1iv
C10eH10A$$$O1v
Compound 2
0.84
0.95
0.95
0.95
0.99
1.81
2.59
2.53
2.53
2.41
2.652(2)
3.414(3)
3.261(3)
3.410(3)
3.176(3)
178
145
134
154
133
O2eH2O$$$N7vi
C2eH2$$$O1vii
C5eH5$$$O1viii
C9eH9B$$$O1ix
0.84
0.95
0.95
0.99
1.84
2.45
2.34
2.59
2.670(3)
3.235(3)
3.283(3)
3.287(3)
171
140
172
127
Symmetry codes: (i) exþ1, eyþ1, ze1/2; (ii) x, yþ1, z; (iii) xe1/2, eyþ2, z; (iv)
exþ1/2, y, zþ1/2; (v) exþ1, eyþ1, zþ1/2; (vi) ex, yþ1/2, ezþ3/2;; (vii) xþ1/2,
eyþ3/2, ezþ1; (viii) xþ1, y, z; (ix) ex, ye1/2, ezþ3/2.
(symmetry codes in Table 2) form the zigezag tapes in crystallo-
graphic b direction and similarly to 1, respective R22(8) ring motifs
are also observed.
Similar zigezag tapes have been found in the crystal structure of
previously reported HIP-2-ac [11], however in the latter case
zwitterions are connected by NeH$$$O and CeH$$$O interactions.
Stabilization of the three-dimensional crystal lattices in 1 and 2 is
provided by CeH$$$O-type contacts between neighboring zigezag
tapes (Figs. 2 and 3, Table 2).
Fig. 1. Asymmetric units of
Displacement ellipsoids are drawn at 50% probability level. (
methylene H atoms of 1 given in green are discussed in details in a paragraph 3.4.). (For
interpretation of the references to colour in this figure legend, the reader is referred to
the web version of this article).
1
(a) and
2
(b) showing atom-numbering schemes.
(CeH) vibrations of
n
O2eH2$$$N1i and C10eH10A$$$O1v contacts (symmetry codes in
Table 2) stabilizing the zig-zag motif in the crystallographic c di-
rection. The above mentioned interactions lead to formation of ring
motifs that can be described by R22(8) graph set notation [30]. In 2,
corresponding O2eH2O$$$N7vi and C9eH9B$$$O1ix interactions
3.3. Hirshfeld surface analysis
Inspection of corresponding Hirshfeld surfaces can provide an
additional, qualitative and quantitative insight into similarities and
differences between interactions in the two reported herein
compounds.

A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
157
Fig. 2. A packing diagram for 1 showing selected CeH$$$O interactions between neighbouring zigezag tapes (shown in blue, orange and tan) in the crystallographic ac plane.
Hydrogen bonds are indicated as orange dashed lines. Symmetry codes are given in Table 2. (For interpretation of the references to colour in this figure legend, the reader is referred
to the web version of this article).
Fig. 3. A packing diagram for 2 showing selected CeH$$$O interactions between neighbouring zigezag tapes (shown in dark yellow, magenta and green) in the crystallographic bc
plane. Hydrogen bonds are indicated as orange dashed lines. Symmetry codes are given in Table 2. (For interpretation of the references to colour in this figure legend, the reader is
referred to the web version of this article).
As discussed above, analysis of interactions and packing in 1 and
2 reveals presence of OeH$$$N hydrogen bonded zigezag tapes,
combined into a three-dimensional crystal lattice by means of
CeH$$$O interactions. The OeH$$$N short contacts formed be-
tween carboxylic substituents and imidazole nitrogen atoms are
visible on corresponding dnorm Hirshfeld surfaces as red areas
(Fig. 4a), whereas on respective fingerprint plots (Fig. 4b) sharp
spikes in the upper (H$$$N, donor) and lower (N$$$H, acceptor)
region can be seen. Comparable lengths of spikes illustrate similar
D$$$A distances in both compounds. In total the H$$$N/N$$$H
contacts contribute to 22.6% and 16.8% of surface areas in 1 and 2,
respectively (Fig. 5).
Weaker CeH$$$O type interactions (Table 2) can be seen on
corresponding dnorm plots as pale-red areas (Fig. 4a) and contribute
to two short H$$$O/O$$$H spikes in the fingerprint plots (Fig. 4b). In
all, H$$$O/O$$$H contacts constitute 26.1% and 20.4% Hirshfeld

158
A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
Fig. 4. (a) Hirshfeld surfaces of 1 (upper) and 2 (lower) showing views of dnorm (from ꢂ0.5 Å (blue) to 0.5 Å (red)) as well as selected atom labels; (b) 2D fingerprint plots for 1
(upper) and 2 (lower). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).
Fig. 5. Close contacts contributions to the Hirshfeld surface areas in the crystal structures of 1 and 2 divided into major interaction types (shown in percentage of total Hirshfeld
surface areas).
surface areas in 1 and 2, respectively (Fig. 5).
contact types involving the S atom individually contribute to less
than 5% of the surface, in total they constitute as much as 21.8% of
Hirshfeld surface in the crystal structure of 2.
Interestingly, the dnorm plot shows a distinct pale-red spot cor-
responding to a S$$$O contact (2.999(2) Å). As studied previously,
intermolecular S$$$O contacts are typically arranged in a defined
pattern [31] where nucleophilic atoms are likely to form a contact
along the extension of the primary CeS bond. In case of crystal
structure of 2, a corresponding C8eS1$$$O2 angle equals 161.8(1)ꢁ,
being in acceptable agreement with typically observed geometry.
Remaining pale areas seen in vicinity of molecule backbones
(Fig. 4a) correspond to other types of contacts, including most
dominant H$$$H (26.6% and 20.4% total surface area in 1 and 2,
respectively, seen as short spikes in fingerprint plots (Fig. 4b) and
H$$$C/C$$$H (total 12.7% and 14.2% surface area in 1 and 2,
respectively). The latter can be indicative of CeH$$$
(not discussed here).
A distinct feature of 2 is the presence of a sulfur atom, contacts
of which are visible on the dnorm plot (Fig. 4a). In that case, 10.3% of
the total Hirshfeld surface of 2 is composed by H$$$S/S$$$H contacts
(seen as pale diffuse area in vicinity of sulfur). Whereas other
p interactions

A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
159
Fig. 6. Raman (A, B, C) and IR (D, E, F) spectra of 1 with groups: OH and CH2 (A, D), OD, CHD and CD2 (B, E), OD and CD2 (C, F).
3.4. Spectral analysis of 1 and 2
deuteration causes much more spectral changes than expected for
one stretching and two bending modes of OH group. This problem
can be explained by considering the Raman of 1700e3200 cme1
region presented for 1 together with related IR spectra in Fig. 6.
Comparison of spectra A and C in the 2900e3000 cme1 region
clearly shows that two bands at 2964 and 2932 cme1, corre-
sponding to asymmetric and symmetric CH2 stretching vibrations,
disappeared upon typical three-fold sample 1 recrystallization
from D2O solution, indicating that methylene group was also
deuterated. Our attempt to prepare (by single recrystallization) the
isotopologue with OeH group exclusively deuterated was unsuc-
cessful, but enabled monitoring an interesting feature seen in
The vibrational spectra of HIPM-2-ac (1) and HITZ-6-ac (2) were
interpreted with the aid of DFT calculations and PED analysis of
computed normal vibrations. The calculations were carried out for
single molecules (Fig. S6) and did not consider the OeH$$$N
hydrogen bonding present in the crystalline state. As the normal
modes with contributions of OH group vibrations cannot be
correlated easily with observed bands, the spectra of deuterated
isotopologues 1a and 2a were also collected and compared with
those of parent compounds (Fig. S7).
Visual comparison of mentioned spectra indicates that

160
A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
spectrum B. The intensity lowering of two bands at 2964 and
2932 cme1 is accompanied by raising of two new bands at 2954 and
2941 cme1 (see Fig. 6 inset). Such changes correspond to partial
deuteration of CH2 groups. New bands result from stretching vi-
brations of single CeH bond in the monodeuterated CHD group.
These bands are located between na(CH2) and ns(CH2) which has
been confirmed by DFT calculations where
n
(CeH10A) ¼ 2965 and
n
(CeH10B) ¼ 2964 cme1
.
Similar calculations for parent compound 1 gave na(CH2) ¼ 2983
and ns(CH2) ¼ 2945 cme1 (mentioned calculated wavenumbers are
0.96 scaled). Wavenumber comparison of observed (Fig. 6 inset)
and calculated n(CeH) vibrations for CHD group shows that former
are more separated (13 cme1) than latter (1.0 cme1). Larger sepa-
ration may be explained by different interaction of methylene
hydrogen atoms with neighbor molecules. The X-ray measure-
ments show that only H10A atom of 1 (see Fig. 1a for atom
numbering and Table 2) is involved in CeH$$$O contact. Thus,
assuming typical “red shift” of
n(CeH) energy upon hydrogen bond
formation [32], the band at 2941 cme1 can be attributed to the
n
n
(CeH10A) stretching vibration, whereas band at 2954 cme1 to
(CeH10B) mode. The (CꢂD) counterparts of discussed CHD group
n
vibrations are observed as broader band centered at 2180 cme1
.
Besides this band, two other bands at 2222 and 2150 cme1 reveal
that fully deuterated CD2 groups are also present (compare with
spectrum C in Fig. 6). Spectrum C also confirms that after three-fold
recrystallization from D2O solution, the methylene group deuter-
ation is almost complete. Additional band at 2357 cme1, which
Raman intensity grows along the deuteration progress, probably
results from the overtone of 1322 cme1 strong vibration. The
deuteration of methylene group is also confirmed by respective IR
measurements (spectra E and F in Fig. 6).
These observations are strongly supported by 1H NMR studies in
solution. To gain insight into H/D exchange in CH2 groups of 1, the
spectra of its D2O solution were recorded as a function of time
(Fig. 7, for full spectra see Figs. S8 and S9). It would be evident, that
the CH2 resonance disappears almost completely within ca. three
days and only small intensity signal attributed to CHD group is
present in the spectrum. Similar result confirming almost complete
deuteration of CH2 groups in D2O solution was obtained for triply
deuterated 1a. Interestingly, analogous experiment performed for 2
revealed much less effective replacement of its methylene
hydrogen atoms by deuterium. Therefore, we attempted to avoid H/
D exchange in the CH2 groups by using CD3OD for recrystallization
of 2. A complete suppression of H/D exchange in CH2 groups of 2a is
confirmed by its 1H NMR spectrum (Fig. 7g) and clearly reflected in
Raman spectrum, where bands at 2965 and 2920 cmꢂ1 were fully
preserved.
The observed positions of vibrational bands and their assign-
ments are summarized in Table 3 for 1, 1a and Table 4 for 2, 2a,
respectively. The wavenumber correlation between corresponding
IR and Raman bands is very good, as has been presented graphically
in Fig. S10 and as it results from MAE values not exceeding the
2.5 cmꢂ1. Since the main goal of this work was the characterization
of the observed spectra, the normal modes of extremely low IR
intensities and Raman activities were excluded and are not listed in
respective Tables. Special attention was paid on vibrations of hy-
droxyl and methylene groups involved in hydrogen bonds, which
may substantially change their wavenumbers and cause larger
discrepancies with respective calculated values. Fortunately, both
groups in 1 are sensitive to deuteration and recorded H/D substi-
tution spectral effects were used for respective band detection.
Comparison of normal vibrations collected for 1 and 1a in Table 3
shows that thirteen modes are changed upon deuteration in the
1800e400 cmꢂ1 region. The contributions of deformation modes of
OH and CH2 groups have been found in ten of these modes, which
Fig. 7. The H-6/H-2 and CH2 resonances in the 1H NMR spectra of D2O solutions of 1
(aec) and 2 (def) measured for freshly prepared samples, after one day and after three
days, respectively, and spectrum of CD3OD solution of 2a (g). Integrals are given in red.
For the sake of clarity signals of solvents are removed. (Complete spectra and their
assignments are given in Figs. S1eS4). (For interpretation of the references to colour in
this figure legend, the reader is referred to the web version of this article).
are more than expected (two for OH and four for CH2 in discussed
wavenumber region). This is a result of coupling of d(OH) and g(OH)
with other internal modes as well as of additional contribution of
rr(CH2) in 511 cmꢂ1 normal vibration. The remaining deformation
modes of methylene group are coupled in different extent. The
scissoring and twisting internal modes show 75 and 88% PED
contributions in 1475 and 1234 cmꢂ1 normal vibrations, whereas
the highest contributions of wagging and rocking modes are 32 and
36% in 1429 and 993 cmꢂ1 vibrations, respectively. All these vi-
brations were attributed to observed bands sensitive to

A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
161
Table 3
Selection of observed and calculated IR and Raman bands [cme1], attributed to vibrations of parent HIPM-2-ac (1) and its OD/CD2 isotopologue 1a with their general and PED
based assignments. (Atoms numbering scheme is consistent with that provided in Fig. 1a).
Observeda
Calculated
General assignmentb,c
Selected PED termsc (mostly ꢃ 10%)
1
1a
Raman IR
1
1a
IR
Raman [IR int, R
activ]
[IR int, R
activ]
2965w 2964m
2928w 2932m
2983d
[1,29]
2945d
[8,90]
na(CH2)
ns(CH2)
na(CD2)
ns(CD2)
n
n
n
n
n
n
n
n
(C10eH10B)-51 þ
(C10eH10A)-50 þ
(C10eD10B)-51 þ
(C10eD10A)-51 þ
n
(C10eH10A)-49
(C10eH10B)-49
(C10eD10A)-49
(C10eD10B)-48
(C10eC11)-10/11
n
2212w 2222m
2165w 2150m
2205d
[1,25]
2145d
[4,80]
1704
[210,4]
1648
[44,20]
1567
n
n
1705s 1694w 1705s 1687w 1717
[210,3]
1618s 1621m 1618s 1621m 1649
[44,20]
1563m 1561s 1560w 1559s 1571
[49,151]
1515s 1521m 1520sh 1521s 1534
[17,37]
1475
[47,28]
1430m 1430m 1428m 1430m 1463
[13,23]
1429
[89,23]
1343m 1344m 1347s 1343s 1378 [5,9] 1385
[62,11]
1348
n
n
n
n
(C]O)
(O1eC11)-86/91 þ
n
(C]C)pm
(C]C)im
þ
þ
n
(NeC)pm
(CeC)
(NeC)pm
(C6eC5)-31þ
(C2eC3)-31þ
n
(N4eC5)-9þ
(C2eC10)-27
n(N8eC7)-7þ
n(N8eC7)-7
n
n
[56,158]
1533
[22,30]
(N]C)im
(CH2)
(NeC)
(CeC) þ rw(CH2)
þ
n
(N1eC7)-24 þ
n(N8eC9)-17
1454m n.o.
d
d
(H10BeC10eH10A)-75
1460 [7,38]
n
n
n
n
n
n
n
n
(N8eC7)-26/29 þ
n(N4eC5)-12
1404m 1406w
(C10eC11)-15 þ
(N4eC3)-14/7 þ
d
(C11eC10eH10B)-11 þ
d
(C11eC10eH10A)-11 þ
n(C2eC10)-10
(CeN)im
(NeC)im
(NeC)im
-
d
(CeH)pm
d(C8eC5eH15)-9/7
1347s 1343m
(N1eC2)-19 þ
(N1eC2)-18 þ
n(N4eC3)-10 þ
n(C3eC2)-10
[50,28]
1319s n.o.
1333 [3,12]
n
n
þ
d(OH)
n
n
d
(C11eO2eH2)-13 þ
n(O2eC11)-12
1322s 1324m
1298 [76,2]
(CeO) þ
(OH)
rt(CH2)
n
(CeC)
(O2eC11)-27 þ
n(C11eC10)-25
1218s n.o.
1186s 1192m
1273 [26,8]
1234 [1,8]
d
d
d
(C11eO2eH2)-21
(C11eC10eH10B)-22 þ
d(C2eC10eH10B)-22 þ
d(C11eC10eH10A)-
22 þ
d(C2eC10eH10A)-22
1241sh 1240s 1226m 1231s 1227 [4,30] 1222 [7,26]
1045m 1050m
d(CH)
d
(H3eC3eN4)-26þ
d
(C2eC3eH3)-22
1087
[439,4]
n(CeO)þ
d
(OH)
n(O2eC11)-54 þ
d(C11eO2eH2)-42
1020m n.o.
1041 [4,21]
n
d
(CeC)pm
(CD2)
n
(C7eC6)-28
1092m 1096w
1067m 1068w
1084 [28,9]
1067
[22,19]
d(H10BeC10eH10A)-68
n(NeC)im
þ
n(CeO) þ rw(CD2)
n(N1eC2)-16 þ
n
(C11eO2)-12 þ
d(C11eC10eH10A)-8 þ
d(C11eC10eH10B)-8
1002m 1004w
958w 953m
1002 [29,4]
993 [15,2]
n
(CeC)
n
(C2eC10)-11
p
(C]O) þ rr(CH2)
(OD) þ (CeO)
(OD)
(C]O)
p
d
(O1eC11, C10, O2)-15 þ
(C11eO2eD2)-26 þ (C11eO2)-10
(C11eO2eD2)-24
d
(C2eC10eH10A)-13 þ
d(C2eC10eH10B)-13
970m 973m
954m 962w
935m 934m
828w n.o.
967 [57,1]
961 [74,20]
d
n
n
n
(CeO) þ
d
p
n
(C11eO2)-31 þ
d
944 [3,3] rt(CD2) þ
d
d
n
(C11eC10eD10B)-23þ
d
d
(C11eC10eD10A)-23 þ
p
(O1eC11, C10, O2)-20
903 [19,3] rr(CD2)
(C2eC10eH10A)-18 þ
(C2eC10eH10B)-18 þ
p(H3eC3, C2, N4)-17
895m 895m
899 [1,24]
n
n
(CeC) þ
(NeC)
n(CeO)
(C10eC11)-43 þ
(N4eC9)-22/16
n(O2eC11)-12
794s
723s
795w 794m 804m 806 [1,36] 799 [21,47]
723w
n
676 [43,2]
d
(im) þ
(OH) þ
(C]O) þ
(C]O)
(CNC)
(C]O)
p
(C]
g
(N1eC2eC3eN4)-21/23 þ
p(O1eC11, C10, O2)-15/9 þ
g
(H2eO2eC11eO1)-10/
(C10eC2, C3, N1)-10
(C6eC7eN8)-6
(C11eC10eH10B)-9
(C5eN4eC3eC2)-11/
O) þ
g
p
(CC)
0 þ
p
(C10eC2, C3, N1)-10/8
(O1eC11, C10, O2)-15 þ
(O1eC11, C10, O2)-8
(N4eC5)-6 þ (C3eN4eC9)-6 þ
(O1eC11, C10, O2)-35
(C11eC10eH10A)-9 þ
(C11eO2eD2)-17
714s
714w
647 [9,3]
d
g
(im) þ
p
p
p
(CC)
g
(N1eC2eC3eN4)-21 þ
p
p
p
675s
675m
642 [124,7]
(OH) þ
(H2eO2eC11eO1)-90 þ
638m 640m 646m 647m 641 [1,17] 640 [1,17]
n
g
(CeN)pm
þ
d
n
g
(N8eC9)-7 þ
n
d
d
520w 525w
530[48,1]
(OD) þ
p
(H2eO2eC11eO1)-65 þ
p
d
n.o.
493m
511 [29,10]
p
(C]O) þ rr(CH2)
p
(O1eC11, C10, O2)-65 þ
d
460w 461w
523[53,29]
d
(OCO) þ
d(OD)
d
g
(O2eC11eO1)-24 þ
d
446w 450m 443w 449m 450 [1,5] 451[15,11]
d(pm) þ
p
(CH14
)
(C7eC6eC5eN4)-26/24 þ
p(H6eC6, C5, C7)-19/18 þ
g
11 þ
g(C9eN8eC7eC6)-9/8
443w 449m 408[36,4]
g
(OD) þ
p
(C]O)
g
(D2eO2eC11eO1)-31 þ þ
p(O1eC11, C10, O2)-27
a
s e strong, m e medium, w e weak, sh e shoulder, n.o. enot observed.
b
na e antisymmetric stretching,
n
s e symmetric stretching,
de bending in-plane,
r
t e twisting, w e wagging, r e rocking, pe bending out-of-plane, ge torsion, im/pm e
r
r
imidazole/pyrimidine ring.
c
e the slash separates the PED values for parent and deuterated compound.
e calculated wavenumbers were scaled by 0.96.
d
deuteration. For example, the CH2 twisting mode, calculated at
deuteration also confirmed the localization of bands related to vi-
1234 cmꢂ1, was not attributed to nearest Raman band at 1240 cmꢂ1
,
brations only partially affected by H/D replacement. One of such
but to band at 1192 cmꢂ1 because in the 1250e1150 cmꢂ1 region,
vibrations is the
which has no counterpart in the theoretical spectra of deuterated
n
(CeC) þ
n
(CeO) mode calculated at 899 cmꢂ1
this is the only band which disappears upon deuteration. The

162
A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
Table 4
Selection of observed and calculated IR and Raman bands [cme1] attributed to vibrations of parent HITZ-6-ac (2) and its OD isotopologue 2a with their general and PED based
assignments. (Atoms numbering scheme is consistent with that provided in Fig. 1b).
Observeda
H2O
Calculated e 0.96 scaled General assignmentb,c
Selected PED termsc (mostly ꢃ 10%)
D2O
H2O
D2O
IR
Raman IR
Raman [IR int, R
activ]
[IR int, R
activ]
n.o.
2966m 2965w 2965m 2998d
[2,28]
2998d
[2,28]
2940d
[12,80]
1708
[190,4]
1607
[48,101]
na(CH2)
ns(CH2)
n(C9eH9A)-50 þ
n(C9eH9B)-50 þ
n(O1eC10)-86 þ
n(C8eC3)-44
n
(C9eH9B)-50
(C9eH9A)-49
(C9eC10)-10
2915w 2923m 2918w 2920m 2940d
[12,80]
1704m 1699w 1698s 1692w 1717
[205,4]
1567m 1569s 1567m 1568s 1607
[48,101]
n
n(C]O)
n
n(C]C)th
1543m 1547w 1544m 1546w 1586 [1,7] 1586 [1,7]
n
n
(C]C)im
(C]N)im
n
n
(C6eC5)-33 þ
(N7eC2)-33 þ
n
d
(C6eC9)-22
(H9BeC9eH9A)-25
(N7eC8)-17
1448m 1458w 1454s 1461w 1485
[60,12]
1485
[60,12]
1477
þ
d(CH2)
d(H9BeC9eH9B)-52 -
n
1477
[90,12]
[93,13]
1331s 1339w 1325s 1314m 1314 [5,15]
1232m n.o.
d
n
n
n
(OH) þ
n
(CeO)
d
(C10eO2eH2O)-25 þ
n
(O2eC10)-14
(O2eC10)-11
(C10eO2eH2O)-14
n(N7eC8)-11
1281 [7,19]
(CeN)im
þ
n(CeO)
n
n
n
(N7eC6)-21 þ
n
1214s n.o.
1231 [22,4]
(CeN)im
(CeO)þ
þ
d(OH)
(N7eC6)-21 þ
d
1184m 1189m
1181
[160,15]
n
(CeN)im
(O2eC10)-21 þ
1178s 1181m
1088
[328,8]
n(CeO) þ
d
(OH)
n(O2eC10)-40 þ
d
(C10eO2eH2O)-32
1000s 1001m 999m 999m 986 [24,15] 989 [7,23]
n
n
n
n
p
p
p
(CeN)im
(CeO)þ
(CeC) þ
n
n
n
n
p
p
p
(N7eC6)-23/21
(O2eC10)-45 þ
(C9eC10)-41 þ
(C9eC10)-25 þ
1077m 1080w
965 [151,7]
d(OD)
d
(C10eO2eD2O)-42
897m 902m
905 [6,22]
n(CeO)
n
d
(O2eC10)-13
(C10eO2eD2O)-17
(H2eC8, C3, S1)-28
858m n.o.
862m 864w 869m 877m 895 [2,8]
876 [5,12]
895 [2,8]
(CeC)þ
d(OD)
(CH10) -
(CH)im
(CH12) þ
p
(CH12
)
(H3eC3, C5, N4)-68 þ
p
768s 768vw 766m 765w 810 [49,4] 810 [49,4]
746s 746m 743m 744m 739 [34,1] 739 [34,1]
725s 720w 719s 719w 706 [3,20] 705 [4,22]
666s 670w 665s 666w 673 [24,1] 673 [41,2]
(H5eC5, C6, N4)-95
(H2eC8, C3, S1)-37 þ
p
(CH10) þ t1(im)
(CH10) -t1(im)
p
(H3eC3, C8, N4)-28 þ
p(N4eC2, N7, S1)-17
n(SeC)
n(S1eC8)-40/42
p
(CH12) þ
p
p
g
g
(H2eC8, C3, S1)-39/42 þ
p
(N4eC2, N7, S1)-27/28þ (H3eC3, C8, N4)-13/14þ
p
(C2eN7eC6eC5)-12/11
(H2OeO2eC10eO1)-84 þ
692m 695w
597w 599m
640 [106,5]
626 [26,6]
g
n
n
(OH) þ
(SeC) þ
(SeC)
p
(C]O)
p(O1eC10, C9, O2)-9
d
(OCO)
n
(S1eC8)-17 þ
d(O1eC10eO2)-12
592w 594m
553m 557m
611 [9,2]
n(S1eC8)-21
568w 568m
574 [35,17]
d(OCO)
d(O1eC10eO2)-15
547 [30,19]
d
n
(OCO)þ
d(OD)
d
n
n
(O1eC10eO2)-16 þ
d
(C10eO2eD2O)-14
(S1eC2)-14
(N7eC2eS1)-11/10
555s 559m 553m 557m 540 [15,20] 538 [37,19]
(SeC)
(S1eC2)-18 þ
(S1eC2)-19 þ
d
d
(C8eS1eC2)-12/n
448m 449w 447m 448w 458 [5,3]
455 [9,4]
n(SeC) þ
d(NCS)
a
s e strong, m e medium, w e weak, sh e shoulder, n.o. e not observed.
b
na e antisymmetric stretching,
ns e symmetric stretching, de bending in-plane, rt e twisting, rw e wagging, rr e rocking, pe bending out-of-plane, ge torsion, im/th e
imidazole/thiazole ring.
c
e The slash separates the assignment for parent and deuterated compound.
e calculated wavenumbers were scaled by 0.96.
d
compound 1a. Similar behavior shows the 895 cmꢂ1 IR and Raman
band not observed in the spectrum of deuterated compound.
As expected for 2, almost exclusive deuteration of carboxylic OH
groups caused less spectral changes than in case of 1. Comparison of
IR spectra of 2 and 2a shows intensity decrease for group of bands
between 1335 and 1295 cmꢂ1 as well as bands at 1214, 1178, 897,
692 and 568 cmꢂ1 whereas new bands are observed at 1232, 1077
and 858 cmꢂ1 in spectrum of 2a. As results from theoretical cal-
be attributed to the nearest positioned bands, without knowing
that this is erroneous.
In general, most of the measured bands were well correlated
with calculated normal modes which characterization in PED terms
also describes the vibrational character of correlated bands.
Exception was made for bands observed below 400 cmꢂ1. The
bands observed there are much more intense than theoretically
predicted normal vibrations. This suggests that the vibrations of
hydrogen bonds and lattice modes contribute in this region. This
assumption is also supported by very high intensity of Raman
bands at 138, 104 and 98 cmꢂ1 (compound 1) and at 119 and
80 cmꢂ1 (compound 2), which is typical for molecular crystals.
culations, first three changes are caused by d(OH) bending vibra-
tion, which contributes in three normal modes at 1314, 1231 and
1088 cmꢂ1 together with stretching vibrations of CeN and CeO
bonds. The band at 897 cmꢂ1 shifts to 858 cmꢂ1 as a result of
additional coupling with
to torsion vibration of hydroxyl hydrogen, calculated at 640 cmꢂ1
The deuteration effect of the lowest wavenumber band (568 cmꢂ1
is a shift of
(OCO) vibration, predicted at 574 cmꢂ1 for 2 and at
547 cmꢂ1 (coupled with
(OD)) for 2a. For some of the recently
d
(OD). Vanishing of 692 cmꢂ1 band is due
.
)
4. Conclusions
d
Imidazo[1,2-a]pyrimidin-2-yl-acetic acid (HIPM-2-ac, 1) and its
analog containing imidazo[2,1-b]thiazole ring (HITZ-6-ac, 2) were
synthesized and structurally characterized by single-crystal X-ray
diffraction. Both compounds crystallize as electrically neutral
molecules in non-centrosymmetric Pca21 and P212121 space groups
d
presented modes, the difference between calculated and observed
wavenumbers is relatively large, but this is the advantage of per-
forming deuteration. Otherwise, these calculated vibrations would

A. Dylong et al. / Journal of Molecular Structure 1117 (2016) 153e163
163
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Acknowledgments
Financial support by a statutory activity subsidy from the Polish
Ministry of Science and Higher Education for the Department of
Chemistry of Wroclaw University of Technology is gratefully
acknowledged. We also gratefully acknowledge the instrumental
grant 6221/IA/119/2012 from Polish Ministry of Science and Higher
Education, which supported our Integrated Laboratory of Research
and Engineering of Advanced Materials where IR measurements
were performed.
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