Intra- and intermolecular hydrogen bonding and conformation in 1-acyl thioureas: An experimental and theoretical approach on 1-(2-chlorobenzoyl)thiourea

Article abstract of DOI:10.1016/j.saa.2015.02.042

The vibrational analysis (FT-IR and FT-Raman) for the new 1-(2-chlorobenzoyl)thiourea species suggests that strong intramolecular interactions affect the conformational properties. The X-ray structure determination corroborates that an intramolecular N-H?OC hydrogen bond occurs between the carbonyl (-CO) and thioamide (-NH₂) groups. Moreover, periodic system electron density and topological analysis have been applied to characterize the intermolecular interactions in the crystal. Extended N-H?SC hydrogen-bonding networks between both the thioamide (N-H) and carbamide (NH₂) groups and the thiocarbonyl bond (CS) determine the crystal packing. The Natural Bond Orbital (NBO) population analysis demonstrates that strong hyperconjugative remote interactions are responsible for both, intra and intermolecular interactions. The Atom in Molecule (AIM) results also show that the N-H?Cl intramolecular hydrogen bond between the 2-Cl-phenyl ring and the amide group characterized in the free molecule changes to an N?Cl interaction as a consequence of crystal packing.

Full text of DOI:10.1016/j.saa.2015.02.042

Accepted Manuscript
Intra- and Intermolecular Hydrogen Bonding and Conformation in 1-Acyl Thi-
oureas: An Experimental and Theoretical Approach on 1-(2-Chlorobenzoyl)thi-
ourea
Aamer Saeed, Asma Khurshid, Michael Bolte, Adolfo C. Fantoni, Mauricio F.
Erben
PII:
S1386-1425(15)00194-8
http://dx.doi.org/10.1016/j.saa.2015.02.042
SAA 13332
DOI:
Reference:
Spectrochimica Acta Part A: Molecular and Biomo-
lecular Spectroscopy
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Revised Date:
Accepted Date:
10 October 2014
2 February 2015
9 February 2015
Please cite this article as: A. Saeed, A. Khurshid, M. Bolte, A.C. Fantoni, M.F. Erben, Intra- and Intermolecular
Hydrogen Bonding and Conformation in 1-Acyl Thioureas: An Experimental and Theoretical Approach on 1-(2-
Chlorobenzoyl)thiourea, Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy (2015), doi: http://
dx.doi.org/10.1016/j.saa.2015.02.042
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Intra- and Intermolecular Hydrogen Bonding and Conformation in 1-Acyl
Thioureas: An Experimental and Theoretical Approach on 1-(2-
Chlorobenzoyl)thiourea
Aamer Saeed,a* Asma Khurshid,a Michael Bolte,b Adolfo C. Fantoni,c Mauricio F.
Erbend,*
a Department of Chemistry, Quaid-I-Azam University, Islamabad 45320, Pakistan.
b Institut für Anorganische Chemie, J.W.-Goethe-Universität, Max-von-Laue-Str. 7, D-
60438 Frankfurt/Main, Germany.
c
Instituto de Física La Plata, Departamento de Física, Facultad de Ciencias Exactas,
Universidad Nacional de La Plata, 49 y 115, La Plata, Buenos Aires, República
Argentina.
d
CEQUINOR (UNLP, CONICET-CCT La Plata), Departamento de Química, Facultad
de Ciencias Exactas, Universidad Nacional de La Plata, C.C. 962 (1900). La Plata,
Buenos Aires, República Argentina.
Corresponding authors:
Tel/Fax: +92-51-9064-2128;+92-51-9064-2241, E-mail: aamersaeed@yahoo.com,
(A.S.) Tel/Fax: ++54-221-425-9485, E-mail: erben@quimica.unlp.edu.ar (M.F.E.)

Abstract
The vibrational analysis (FT-IR and FT-Raman) for the new 1-(2-
chlorobenzoyl)thiourea species suggests that strong intramolecular interactions affect
the conformational properties. The X-ray structure determination corroborates that an
intramolecular N–H···O=C hydrogen bond occurs between the carbonyl (–C=O) and
thioamide (–NH2) groups. Moreover, periodic system electron density and topological
analysis have been applied to characterize the intermolecular interactions in the crystal.
Extended N–H···S=C hydrogen-bonding networks between both the thioamide (N–H)
and carbamide (NH2) groups and the thiocabonyl bond (C=S) determine the crystal
packing. The Natural Bond Orbital population analysis demonstrates that strong
hyperconjugative remote interactions are responsible for both, intra and intermolecular
interactions. The Atom in Molecule (AIM) results also show that the N–H···Cl
intramolecular hydrogen bond between the 2-Cl-phenyl ring and the amide group
characterized in the free molecule changes to an N···Cl interaction as a consequence of
crystal packing.
Keywords: Thiourea; Crystal structure; FTIR spectroscopy; Raman spectroscopy;
Hydrogen bond; NBO; AIM topological analysis

1. Introduction
Very recently, Eccles at al. [1] demonstrate the versatility of the thioamide
functional group [–C(S)NH2] as a key moiety for crystal engineering. The related
acetylthiourea species, CH3C(O)NHC(S)NH2, has been known for more than a century
[2] and represents the first example of the 1-acyl-thiourea family of compounds [–
C(O)NHC(S)NH2] [3-5]. Its X-ray structure was early reported [6], resulting in an
molecular structure in which the heavy atoms skeleton are arranged in a planar fashion
with the carbonyl double bond interacting via an intramolecular hydrogen bond with the
–NH2 group. The infrared and Raman spectra were also interpreted in terms of a CS
point group model [7]. More recent quantum chemical calculations on small model
compounds [8] reveal that the central –C(O)NHC(S)NH2 group can display several
conformations, depending on the dihedral values around the acyl-N bond and the
adjacent N–C bond [9].
For 1-(acyl/aroyl)-3-(mono-substituted) thiourea derivatives a local planar
structure of the thiourea moiety is preferred, with opposite orientation between the C=O
and C=S double bonds (“S-shape”) [10]. In this conformation, a pseudo six-membered
ring structure promotes a C=O···H–N intramolecular hydrogen bond. On the other
hand, when the formation of a suitable hydrogen bond is prevented, as in 1-(acyl/aroyl)-
3,3-(di-substituted) thiourea derivatives (R2, R3 ≠ H), the anticlinal geometry (U form)
is preferred [11-14].
The understanding of the conformational properties on these compounds has
direct relevance in applied fields, including chemosensors for selective and sensitive
naked-eye recognition for anions [15-18] and new developments on biological [19] and
pharmaceutical applications [20-22]. As has been recognized, the success of many of
these applications of 1-acyl thioureas, rely on the formation of proper hydrogen bonds

with particular receptors [23]. The 2-chlorophenylthiourea compound effectively
coordinate zinc (II) cations in the presence of acetylacetonate forming a screw shaped
square–pyramidal coordination compound with promising application in nonlinear
optics [24].
Continuing our project dedicated to the study of 1-(acyl/aroyl)-3-(mono-
substituted) thioureas [25,26], in this article the preparation of the novel species 1-(2-
chlorobenzoyl)thiourea is presented. It is interesting to note that although several
thioureas containing the 1-(2-chlorobenzoyl) group with different degree of substitution
at the second nitrogen atom have been reported [27-31], the non-substituted species
remains unknown. In this work, the molecular and crystal structures in conjunction with
the vibrational properties have been determined by X-ray diffraction and spectroscopic
(infrared and Raman) analysis of the solid. These studied have been complemented by
quantum chemical calculations. In particular the Natural Bond Orbital (NBO) [32,33]
population analysis has been performed in order to evaluate the donor→ acceptor intra
and intermolecular interactions for the monomer and also for dimer and trimer
arrangements of molecules. Finally, to better characterize the intermolecular
interactions present in the crystal and the possible effect of packing in the
intramolecular interactions, the topology of the electron density obtained from a
periodic quantum calculation has been analyzed by using the atoms in molecules (AIM)
approach [34].
2. Experimental
2.1 Synthesis and characterization.
Following the method reported for related species [35], freshly prepared 2-
chlorobenzoyl chloride was added to a solution of potassium thiocyanate in acetone to

get the corresponding isothiocyanate via stirring at room temperature for 1 hour. The in
situ formed 2-chlorobenzoyl isothiocyanate was treated with aqueous ammonia at low
temperature. On completion of the reaction mixture was poured in ice cold water and
the solid product obtained was recrystallized from ethanol to afford yellow crystalline
solid.
1
Yield: 85%; m.p: 152 °C; IR (cm–1): 3329, 3153, 1687, 1236; H-NMR (ppm, CDCl3,
300MHz): 11.64 (s, CONH, 1H), 9.64 (CSNH2, 2H), 7.52 (m, 3H, Ar), 7.41(m, 1H Ar);
13C-NMR (CDCl3, 75MHz): 182.0 (C=S), 167.7 (-CO), 135.0, 132.3, 130.31, 130.0;
GC-MS: 139 (M+), 111, 85, 75, 44; Elemental analysis: Calcd. For C8H7ClN2OS C:
44.76, H: 3.29, N: 13.05, S: 14.94%. found C: 44.70, H: 3.11, N: 13.02, S: 14.90%.
2.2- Instrumentation.
Melting point was determined using a digital Gallenkamp (SANYO) model
1
MPDBM3.5 apparatus and was uncorrected. HNMR and 13C NMR spectra were
determined in CDCl3with a 300 MHz Bruker AM-300 spectrophotometer. Mass Spectra
(EI, 70eV) were taken on a GC-MS, Agilent technologies 6890N with an inert mass
selective detector 5973 mass spectrometer and elemental analyses were conducted using
a LECO-183 CHNS analyzer.
2.3- Vibrational Spectroscopy.
Solid-phase (in KBr pellets) infrared spectra were recorded with a resolution of
2 cm–1 in the 4000-400 cm–1 range on a Bruker EQUINOX 55 FTIR spectrometer. FTIR
spectra (ATR) were recorded on an a Bio-Rad-Excalibur Series Mode FTS 3000 MX
spectrophotometer. The FT-Raman spectra of the powdered solid sample were recorded
in the region 4000-100 cm–1 using a Bruker IFS 66v spectrometer equipped with

Nd:YAG laser source operating at 1.064 µm line with 200 mW power of spectral width
2 cm–1.
2.4- Computational details.
Molecular quantum chemical calculations have been performed with the
GAUSSIAN 03 program package [36] by using the B3LYP DFT hybrid methods
employing Pople-type basis set [37]. The moderate 6-31G(d,p) basis set has been
applied for the relaxed scan calculations, whereas the extended valence triple-ξ basis set
augmented with diffuse and polarization functions in both the hydrogen and weighty
atoms [6-311++G(d,p)] has been used for geometry optimization and frequency
calculations. The calculated vibrational properties corresponded in all cases to potential
energy minima for which no imaginary frequency was found. The recommended scale
factor of 0.96 has been applied for analyzing the theoretical harmonic vibrational
frequencies [38]. Periodic calculations were performed at the B3LYP/6-31G(d,p) level
with Crystal98 and Crystal09 codes [39,40]. Using the experimental estimations as the
starting point, the coordinates of the hydrogen atoms in the crystal were optimized to
minimize the B3LYP/6-31G(d,p) crystal energy with heavy atom coordinates and cell
parameters fixed at their experimental values. The topology of the resulting electron
density was then analyzed using the TOPOND98 program [41]. For consistency with
the periodic results, molecular and supramolecular electron densities were also analyzed
with TOPOND98 from calculations performed with Crystal98 using geometry
optimized with Crystal09.
2.5- X-Ray Data Collection and Structure Refinement. X-ray data were collected on a
STOE IPDS-II diffractometer with graphite-monochromated MoKα radiation. An
empirical absorption correction with the PLATON program [42] was performed. The
structure was solved by direct methods and refined with full-matrix least-squares on F2

using the program SHELXL97 [43]. H-atoms bonded to carbon atoms were placed on
ideal positions and refined with fixed isotropic displacement parameters using a riding
model. H-atoms bonded to N were freely refined. Full crystallographic data have been
deposited with the Cambridge Crystallographic Data Centre (CCDC). Enquiries for data
can be directed to: Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge, UK, CB2 1EZ or (e-mail) deposit@ccdc.cam.ac.uk or (fax) +44 (0) 1223
336033. Any request to the Cambridge Crystallographic Data Centre for this material
should quote the full literature citation and the reference number CCDC 988811.
3. Results and Discussion
3.1- Synthesis and characterization
The title compound was prepared by reaction of 2-chlorobenzoylisothiocyanate
with aqueous ammonia at low temperature. The isothiocyanate was obtained in situ by
stirring 2-chlorobenzoyl chloride with potassium thiocyanate in dry acetone at room
temperature for one hour. The product was re-crystallized from ethanol as yellow
crystals in high yield. The 1H NMR spectrum showed singlets of one and two protons at
δ 11.64 and 9.64 ppm for CONH, and CONH2 respectively besides the multiplets at
7.52-7.41 for aromatic protons. In 13C NMR the characteristic thiocarbonyl and
carbonyl carbons appeared at 182.0 and 167.7 ppm, respectively, in addition to other
characteristic signals.

O
C
O
C
Cl
OH
Cl
SOCl2
KSCN, dry acetone
Stirring, 1h
Cl
Reflux 2 h
O
O
C
H
N
S
C
N
C
S
C
NH2
Cl
Cl
aq. NH3
Stirring, 2h
Scheme 1 Synthesis of 1-(2-chlorobenzoyl)thiourea
3.2-Tautomerism and molecular conformation
Thione-thiol tautomerism is plausible for 1-acyl thioureas, the thione form being
strongly preferred [44], although the presence of minor amount of the thiol form in the
solid phase has been suggested [45,46]. This tautomeric equilibrium is similar to that
found for thiobiuret analogs, for which the interplay of conjugative stabilization and
intramolecular hydrogen bonding defines the tautomeric preferences [47]. The two main
tautomeric forms expected for the title compound have been computed at the B3LYP/6-
311++G(d,p) level of approximation and the optimized structure are shown in Figure 1.
According to these calculations, the S-thione form is more stable than the thiol form by
18.2 kcal/mol (∆E° values, including zero point energy) for the molecule isolated in a
vacuum.

O1
C7
N2
N1
C1
C8
C2
S
Thione (S) (0.0)
Thione (U) (13.2)
Thiol (18.2)
Figure 1. Molecular structures optimized [B3LYP/6-311++G(d,p)] for the thione (in the
S and U conformations) and thiol tautormers of 1-(2-chlorobenzoyl)thiourea. Relative
energies values (∆E°, in kcal/mol) are given.
To further inspect the potential energy surface of the thione tautomer, the
potential energy function for internal rotation around the central N–C dihedral angle has
been calculated. The B3LYP/6-31G(d,p) level of approximation has been applied
allowing geometry optimizations with the corresponding dihedral angle varying from 0
to 180º in steps of 10º. The potential energy curve is shown in Figure 2.

18
15
12
9
6
3
0
0
60
120
180
240
300
360
δ(C7N1-C8N2) (Degrees)
Figure 2. Calculated [B3LYP/6-31G(d,p)] potential function for internal rotation
around the δ(C7N1−C8N2) dihedral angle of 1-(2-chlorobenzoyl)thiourea. For atom
numbering see Figure 1.
A clear minimum at δ(C7N1–C8N2)= 0º is observed, corresponding to a local
planar structure of the central –C=O–NH–C=S– moiety, with opposite orientation
between the C=O and C=S double bonds. This conformation corresponds to the S form
showed in Figure 1. Moreover, the structures with δ(C7N1–C8N2)= 180º correspond to
a local maxima in the potential energy curve. Two nearly equivalent local minima are
observed at δ(C7N1–C8N2) values of ca. 150 and 210 degrees, corresponding to non-
planar synclinal conformers (“U” form, see Figure 1) and are located higher in energy
by ca. 13.2 kcal mol–1. These results are in good agreement with the structural analysis

based on 739 structures containing the –C(C=O)N(C=S)N– moiety deposited in the
Cambridge Structural Database [10]. The prevalence for the S conformation is clearly
established for 1-(acyl/aroyl)-3-(mono-substituted) thiourea derivatives, showing a local
planar structure of the central –C(O)–NH–C(S)–NH– moiety, with opposite orientation
between the C=O and C=S double bonds. In this conformation the C=O and H–N
groups form a pseudo 6-membered ring, favoring an intramolecular interaction through
a hydrogen bond [11,28,48].
The potential energy curve for the rotation of the 2-chlorophenyl ring with
respect to the thiourea group is shown in Figure 3. As expected, the curve is symmetric
with respect to the planar thiourea group, with two minima at dihedral angles of ca. 40
and 130 degrees, the former being more stable by ca. 1 kcal/mol. The occurrence of
planar arrangements between the 2-chlorophenyl and the amide-like groups are
disfavored, the structures with N1C7–C1C2 torsion angle having values of 0º and 180º
being clear maxima in the potential energy curve.

4
2
0
0
60
120
180
240
300
360
δ(N1C7-C1C2) (degrees)
Figure 3. Calculated [B3LYP/6-31G(d,p)] potential function for internal rotation
around the C1-C7 bond, i.e. for the rotation of the 2-Cl-phenyl group with respect to the
amide group of 1-(2-chlorobenzoyl)thiourea. For atom numbering see Figure 1.
3.3 Vibrational Analysis
The FT-IR, attenuated total reflectance (ATR-FTIR) and FT-Raman spectra for
the title compound in the solid phase were measured as KBr pellets and pure powdered
samples, respectively. Very similar FTIR spectra were obtained for the transmittance
and ATR modes, the first one giving slightly better band separations especially in the
1000-400 cm-1 spectral region. The observed wavenumbers and those calculated at the
B3LYP/6-311++G(d,p) level for the S form of the isolated molecule are reported in
Table 1, together with a tentative assignment of the bands. The assignment has been
carried out by comparison with theoretical wavenumbers as well as on comparison with

the reported data for CH3C(O)NHC(S)NH2 [7,49] and related thioureas containing the
chlorobenzoyl group [30,50-52]. Special attention was dedicated to the band assignment
of the normal modes associated with the central acyl thiourea group.
Table 1. Experimental FTIR (in transmittance and attenuated total reflectance modes) and
Raman, as well as theoretical [B3LYP/6-311++G(d,p)] vibrational data (cm-1) with a tentative
assignment for 1-(2-chlorobenzoyl)thiourea.
Experimentala
ATR-FTIR
3329 s
Computedb
Tentative
assignmentc
νas(NH2)
ν(N-H)
FTIR
Raman
3324 s
3545(120)
3453(48)
3350(150)
3075(1)
3246 m
3114 m, br
3058 sh
2988 m
2916 m
2788 m
1684 s
3232 m
3120 m
3122 vw
3063 s
νs(NH2)
3023 w
3063(6)
ν(C–H)´s ring
3024 vw
1682 s
3051(2)
2906(5)
1687 s
1649(206)
1566(22)
1549(390)
1537(21)
ν(C=O)
ν(C=C)
δ(NH2)
ν(C=C)
1619 vs
1598 sh
1603 vs
1598 sh
1619 w
1592 s
1570 m,sh
1547 w
1547 vs
1471 m
1436 m
1403s
1538 vs
1471 m
1434 m
1402 br
1480(747)
1437(18)
1404(25)
1340(270)
δ(N-H)
ν(C=C)
ν(C=C)
νas(NCN)
1437 w
1404 w

1342 w
1315 w
1289 vs
1275 sh
1265 vs
1254 vs
1165 m
1135 s
1350 vw
1312 vw
1280(32)
1265(7)
νs(NCN)
ν(C=C)
δ(C-H)
1235(85)
1195(190)
1140(2)
1279 s
1288 s
1262 sh
1251 s
1166 s
1132 m
ν((O)C-C)
δ(C-H)
1270 sh
1237 vs
1162 m
1122 vs
1117 sh
1049 s
1101(111)
1098(70)
1022(170)
ν(C=C)
ν(C-N(H))
δ(C-H)
1126 sh
1055 s
1054 sh
1039 vvs
1017 m
988 m
1011(93)
δ(CCC)
1049 sh
1019 vs
1005 vs
986 vs
1038 s
1010 vs
967(151)
965(114)
ρNH2
ρ(C–H)
976 sh
937(3)
887(42)
851(2)
ρ(C–H)
δ(CNC)
ρ(C–H)
947 m
953 m
948 vw
913 w
870 m
830 w
801 m
909 w
875 m
912 vs
869 w
828 m
798 s
796 m
766 m
780(31)
766(10)
731(52)
705(20)
ν(C=S)
ρ(C–H)
ρ(C–H)
δ(C–C)
ν(C-Cl)
ρ(NH2)
δ(CCC)
771 m
764 m
744 s
779 w
764 m
745 s,br
695 m
725 w
703 m
695 sh
724 w
681(10)
649(4)
704 vw
694 vw
628(13)

662 sh,m
644 m
641 s
641 s
634 sh
622 vs
565 w
477 s
615(33)
592(42)
528(1)
ρ(NH)
627 m
603 s,br
oop(C=S)
δ(CCN)
δ(CCC)
δ(NCS)
ρ(NH2)
δ(NCN)
δ(CCC)
δ(NCS)
δ(CCCl)
563 w
478 m
468(13)
450(4)
469 vvw
460 m
462 m
425 w
436(159)
418(6)
432 vw
416 w
432 s
412(4)
370 m
358 m,br
347 sh
314 m
269 m
251 m
223 m
190 m
167 m
350(1)
322(17)
249(1)
δ(CCC(O))
234(11)
209(2)
146(1)
103(2)
ρ(C(O))
ρ(NCN)
ρ(NCS)
τ
a FTIR of solid in KBr pellets, ATR-FTIR and FT-Raman of finely powdered solid. Band intensity: vs = very
strong, s = strong, m = medium, w = weak, vw = very weak, vvw = very very weak, sh: shoulder band. b Scaled
computed values for the S form. In parentheses relative band strengths, IR intensities [in Km/mol]. c ν: stretching
(subscripts s and as refer to symmetric and antisymmetric modes, respectively), δ: deformation, ρ: rocking, oop:
out of plane deformation and τ tortional modes.
A series of absorptions appearing in the high energy region (3500-2500 cm–1) of
the infrared spectrum are associated with the N–H and C–H stretching modes. With the
help of quantum chemical calculations, the absorptions appearing at 3324 and 3114 cm–

1 can be assigned to the antisymmetric and symmetric N–H stretching vibration of the –
NH2 group, respectively. The low value corresponding to the symmetric motion is
probably due to the fact that this mode is mostly influenced by the intramolecular
C=O···H–N1 hydrogen bond [53]. The separation between νas(NH2) and νs(NH2) is well
reproduced by the B3LYP/6-311++G(d,p) calculations (203 cm–1) given confidence to
this tentative assignment. A third band located at intermediate values (3246 cm–1) is
assigned to the N–H stretching of the thioamide group [52].
The intense absorption at 1684 cm–1 corresponds to the ν(C=O) stretching
mode,[54,55] in agreement with that found for the parent CH3C(O)NHC(S)NH2 species
occurring at 1680 cm–1 [7]. The computed [B3LYP/6-311++G(d,p)] infrared spectra for
the S form predicts this mode as an intense absorption at 1649 cm–1, whereas for the U
conformer it is computed at 1779 cm-1, in a clear indication that the N1–H···O=C
intramolecular interaction is responsible for the red-shift and high intensity of the
ν(C=O) mode observed for the S form [12,54] [56]. This description is well
complemented by the analysis of the Raman spectrum, where a strong signal appears at
1682 cm–1. It is plausible that the intensity observed for ν(C=O) in the Raman spectrum
is increased by the formation of inter and intramolecular hydrogen bonds [57,58].
The infrared spectrum shows two very strong absorptions at 1619 and 1547 cm–
1, which are tentatively assigned to the δ(N–H) deformation modes on the –NH2 group
and N1–H acyl thiourea group, respectively [56]. Quantum chemical calculations for the
S form confirm the presence of very intense absorptions at 1549 and 1480 cm–1 (scaled
values), whose displacement vectors allow the assignment of these fundamentals to the
δ(N–H) deformation modes. Agreement is also found when the spectra is compared
with those reported for CH3C(O)NHC(S)NH2 and its tri-deuterated analogue [7]. In

effect, the δ(N–H) deformation modes on the –NH2 and –NH– groups contribute to
strong absorptions at 1590 and 1525 cm–1, respectively.
The ν(C=S) stretching is tentatively assigned to the medium intensity absorption
observed at 801 cm–1, with an strong counterpart in the Raman spectrum at 798 cm–1, in
good agreement with the computed value of 780 cm–1 [B3LYP/6-311++G(d,p)] and
with reported data for related species [12,45]. In particular, for CH3C(O)NHC(S)NH2
this mode contributes mainly to the absorption appearing at 820 cm–1 in the infrared
spectrum [7].
3.4- Molecular and crystal structure
1-(2-chlorobenzoyl)thiourea crystallizes in the triclinic space group P-1 (see
Table 2), with two molecules in the asymmetric unit, as shown in Figure 4. Both
molecules are in the S-conformation. A least-square fit of all non-H atoms (r.m.s.
deviation 0.115 Å) shows that there are no remarkable differences between the two
molecules, as can be observed in Figure 5.
The carbonyl oxygen in the amide group is slightly out of the mean plane of the
benzene ring, the N1-C7-C1-C2 torsion angle being 50.8(2)º, in reasonable agreement
with the computed value for the free molecule of 40.9º (see Figure 3). Similar
conformational features were reported for chloro-benzoyl thioureas [59,60]. Bond
lengths and angles in the heavy atom skeletons are within normal ranges [61,62] (see
Tables S5 and S6 in the Supplementary data).
Table 2. Crystal data and structure refinement for 1-(2-chlorobenzoyl)thiourea.
Empirical formula
Formula weight
Temperature
C8H7ClN2OS
214.67
173(2) K

Wavelength
0.71073 Å
Crystal system
Space group
Triclinic
P-1
Unit cell dimensions
a = 8.3240(7) Å, α= 66.197(7)°.
b = 10.5091(10) Å, β= 88.842(7)°.
c = 12.3602(11) Å, γ = 69.805(7)°.
3
Volume
919.48(14) Å
Z
4
3
Density (calculated)
Absorption coefficient
F(000)
1.551 Mg/m
-1
0.600 mm
440
3
Crystal size
0.48×0.47×0.47 mm
Theta range for data collection
Index ranges
3.63 to 25.57°.
-10<=h<=9, -12<=k<=12, -14<=l<=14
7819
Reflections collected
Independent reflections
Completeness to theta = 25.00°
Absorption correction
Max. and min. transmission
Refinement method
Data / restraints / parameters
3416 [R(int) = 0.0267]
99.4 %
Semi-empirical from equivalents
0.7659 and 0.7618
2
Full-matrix least-squares on F
3416 / 0 / 260
2
Goodness-of-fit on F
1.064
Final R indices [I>2sigma(I)]
R indices (all data)
R1 = 0.0274, wR2 = 0.0715
R1 = 0.0297, wR2 = 0.0730
0.020(2)
Extinction coefficient
-3
Largest diff. peak and hole
0.280 and -0.199 e.Å

C4
C6
2
C3
C5
Cl
C2
C1
N1
C7
S
C8
1
O
HB
N2
HA
Figure 4. Asymmetric unit of the title compound in a single crystal at 173 K. Labels 1
and 2 stand for each molecule within the asymmetric unit (anisotropic displacement
ellipsoids drawn at the 50% probability level).
Figure 5. Superposition of the two molecules of the asymmetric unit.

A schematic view along c-axis (see Figure 6) makes evident that 1-(2-
chlorobenzoyl)thiourea crystal can be considered as having a layered structure. At this
respect it is interesting to note that S atoms as well as N–H and NH2 groups are all very
near to the mean planes defined by themselves, parallel to (a,b) and facing each others.
But also Cl atoms are all very near to planes parallel to (a,b) nearly midway along c-
axis between those previously mentioned. As we will see in what follows, those
geometrical features would be closely related to the way molecules interconnect.
Figure 6. View along c-axis of the 1-(2-chlorobenzoyl)thiourea crystal packing.

3.5- Topology analysis of the electron densities
Since many of the more relevant intra and intermolecular interactions involve
hydrogen atoms, their positions in the crystal were optimized at the B3LYP/6-31G(d,p) level,
keeping fixed at their crystallographic values the heavy atom positions and cell parameters.
The electron density topology of this partially optimized crystal structure was then analyzed.
Values of the electron density and positive principal curvature of the Laplacian at the
corresponding (3,-1) critical point were used as indicators of the interaction strength [63].
Topological parameters of the predominant intermolecular interactions are reported in
Table 3. The main two are N–H···S=C interactions connecting each other molecules 1 and 2
of the asymmetric unit (see Figure 7.a). Both of them have very similar topological
characteristics and form a cyclic motif. The only other two interactions with strengths similar
to those previously mentioned connect molecule 1 of a reference asymmetric unit with
molecule 2 generated by [-1+x,y,z], linking the sulfur atom of one molecule to an amino
hydrogen atom of the other one, forming a cyclic motif, as is also shown in Figure 7.a.
2
Following Berstein et al. [64], both yet described motifs can be classified as R2 (8) since they
form pseudo eight-membered rings with two donors and two acceptors each. On geometrical
grounds, the four N–H···S=C interactions involved can be considered hydrogen bonds.
Alternation of both kinds of cyclic motifs gives rise to infinite chains along a axis. Similar
patterns are commonly encountered in 1-acyl-thioureas [14],[65,66]. Only the sulfur atom of
molecule 1 is in addition interacting with two aromatic hydrogen atoms, one belonging to the
molecule 1 generated by [1-x,1-y,-z] and the other to the molecule 2 generated by [1-x,1-y,1-
z], as shown in Figure 7.b. With all probability the slight difference in molecular geometry
between molecules in the asymmetric unit is mainly a consequence of such a difference in
intermolecular interactions. Another medium weak interaction links chlorine atom of
21

molecule 1 with an aromatic hydrogen atom of molecule 2 generated by [1-x,-y,1-z] (see
Figure 7.b).
Table 3. Topological properties (a.u.) and geometrical parameters (Å and °) of the intramolecular
and main intermolecular interactions in the B3LYP/6-31G(d,p) electron density of the 1-(2-
chlorobenzoyl)thiourea crystal and molecule: electron density (ρ), Laplacian (∇2ρ) and positive
principal curvature (λ3) evaluated at the corresponding (3,-1) critical points.
INTERMOLECULAR
Attractors a,b
H···A
2.372
2.368
2.412
2.417
2.797
2.820
2.766
D-H···A
159.3
161.4
160.5
175.7
141.3
160.1
152.1
ρ
∇2ρ
λ3
S(1)
HN1(2)
HN1(1)
0.0210
0.0212
0.0188
0.0184
0.0097
0.0079
0.0083
0.0450
0.0448
0.0437
0.0416
0.0293
0.0253
0.0278
0.0894
0.0896
0.0828
0.0800
0.0446
0.0378
0.0422
S(2)
S(1)
HAN2(2 I)
HAN2(1)
S(2 I)
S(1)
HarC6(1 II)
HarC6(2 III)
HarC4(2 IV)
S(1)
Cl(1)
INTRAMOLECUAR c
∇2ρ
λ3
Attractors
H···A
D-H···A
ρ
O
HBN2
0.0289
0.0327
0.0909
0.1026
0.1639
0.1896
1.953
1.888
127.3
130.7
Cl
N1
0.0120
0.0152
0.0451
0.0589
0.0580
0.0856
2.760
2.470
72.7 d
119.7
HN1
a
Between parenthesis the label identifying molecule, including symmetry code as a
b
superscript. In the second column attractor is the hydrogen atom. Symmetry codes: I: -
1+x,y,z ; II: 1-x,-y,-z ; III: 1-x,1-y,1-z ; IV: 1-x,-y,1-z. c First row: in-crystal molecule; second
row: free molecule. d Though attractor is N1 the value of N1–H⋅⋅⋅Cl is reported.
22

(a)
(b)
Figure 7. Main intermolecular interactions in the crystal of 1-(2-chlorobenzoyl)thiourea. (a)
2
N-H···S=C building R2 (8) motifs. (b) C–Har···S and C–Har···Cl. Between parenthesis the
symmetry operation generating the molecule.
Backing to the layer-like structure described in the previous section, it is worth
noticing that bond paths of the strongest interactions are all around the mean planes parallel to
(a,c) defined by the N1–H and –NH2 groups and S atoms and that could be considered the
layer boundaries. Layers are linked one each other through C–Har···S interactions, while
molecules within a layer are connected through C–Har···Cl interactions and the weakest C–
Har···S ones.
Differences in geometry and electron density topology between the in-crystal and free
molecules deserve some comments. Relevant geometric and topological parameters are
reported in Table 3. Data obtained from a geometry optimization at the B3LYP/6-31G(d,p)
level are used for the free molecule. Packing induces significant changes in some bond
lengths and angles but, most important, in the geometry of the non-bonded intramolecular
contacts. From a topological view point the most significant change on going from the free
molecule to the in-crystal one is the switch from an N–H···Cl hydrogen bond to an H–N···Cl
23

interaction. On geometrical grounds this behavior is consistent with the rather significant
enlargement of the Cl···H distance and decrease of the Cl···H–N angle, whose value in the
crystal is far outside the accepted range for hydrogen bond interactions [67].
In order to get more hints on this behavior we decided to perform a supramolecular
geometry optimization on the isolated asymmetric unit molecular pair. Though changes in the
pair geometry with respect to the in-crystal one are observed, molecular geometry is closer to
that within the crystal than to the free molecule one. More importantly, from a topological
view point intramolecular interactions in the pair resemble those in the crystal. Although
contributions from other intermolecular interactions are expected, the rather drastic changes in
molecular geometry and electron density topology on going from the free to the in-crystal
molecule can then mainly be attributed to interactions within the asymmetric unit.
3.6-Natural Bond Orbital Analysis
It has been suggested that electronic donor-acceptor interactions between remote
orbitals deserve close inspections owing to the influence they can play on the backbone
conformation [68]. In the frame of the Natural Bond Orbital (NBO) population analysis the
energy of these donor–acceptor interactions can be estimated by the second order perturbation
theory [69].
Recently, we have demonstrated that a remote lpO→ σ*(N–H) interaction takes place
for the S form in acyl-thiourea species [70], amounting to as much as 12.03 kcal/mol, a value
that is higher than that found for benzenesulfonylamin acetamide molecules (9.5 kcal/mol)
[71]. This remote lpO→ σ*(N2–H) hyperconjugative interaction can be also confirmed as
acting in the title species. In effect, the second order perturbation analysis performed at the
B3LYP/6-311++G(d,p) level of approximation, computes a donor-acceptor stabilization
energy of 8.2 kcal/mol, which is responsible for the electrostatic character present in
“classical” C=O···H–N2 hydrogen bond [72]. It is worth noting that this remote interaction
24

occurs through the pseudo-six member ring and; due to the orientation request for the orbital
overlapping, it is feasible only for the S conformation.
Interestingly, in agreement with the topological analysis, a remote interaction of the
type lpCl→ σ*(N1–H) is observed, involving the pseudo-six member formed between the C–
Cl and the H–N1 group in the 2-chlorobenzyl amide moiety. This partial transfer of a lone
pair of electrons of chlorine atom to the N1–H antibonding orbital corresponds to a weak (1.4
kcal/mol) but undoubtedly important interaction.
In order to scrutinize the donor→ acceptor interactions between molecules, the NBO
analyses have also been applied for a dimer and trimer arrangement of molecules as observed
in the crystal structure. Thus, starting from the positions found in the X-ray analysis,
optimization of the geometry and NBO analysis at the B3LYP/6-311++G(d,p) level of
approximation have been performed. The optimized structures are shown in Figures S1 and
S2 given as supporting material.
For the centro-symmetric dimer, the computed C=S bond length (1.681 Å) is longer
than that computed for the monomer (1.669 Å), whereas the N1–C8 bond length is longer in
the monomer than that of the dimer, with values of 1.403 and 1.390 Å, respectively. Similar
trends are observed in the trimer arrangement, with the C=S bond distance of molecule 1
elongated up to 1.696 Å with an N1–C8 bond length of 1.390 Å. The computed hydrogen
bond is characterized by a S···H–N1 distance of 2.46 Å and S···H–N1 angle of 161.3° in the
dimer. When the trimer is analyzed, similar values are observed between molecules 1 and 2,
with S···H(N1) distance and S···H–N1 angle of 2.45 Å and 165.6°. The second C=S···H–N2
interaction –with the molecule located at (-1+x,y,z) occurring through the -C(S)NH2 group,
see Figure 7.a- is characterized by S···H(N2) distance and S···H–N2 angle of 2.44 Å and
170.4°, respectively. The experimental mean values are 2.56(2) and 2.55(2) Å for the S···H–
25

N distances and 161(2)° and 167.2° for the bond angles of the C=S···H–N interactions
involving the N1 and N2 nitrogen atoms, respectively (see Table 3 for comparison).
The second order perturbation analysis clearly identified the electron donation from
the sulfur lone pair orbitals of one molecule toward the σ*(N1–H) antibonding orbital
formally localized on the amide-like group of the second molecule in the dimer. The remote
lpS→ σ*(N1–H) interaction between the two units in the dimer amounts as much as 12.9
kcal/mol. This electron donation is also observed in the trimer arrangement with a similar
strength (13.1 kcal/mol).
The C=S···H–N2 interaction involving the –NH2 terminal group was analyzed by
studying the donor-acceptor electron donation between molecule 1 and the second molecule
located at the (-1+x,y,z) position (see Figure 7.a). In this case, the remote lpS→ σ*(N2–H)
interaction amounts to 12.5 kcal/mol [σ*(N2–H) antibonding orbital formally localized on the
–NH2 group].
Thus, the NBO analysis allows interpreting the intramolecular C=S···H–N hydrogen
bonds involving the thiourea group as (remote) donor→ acceptor electron transfer between
the lone pair electrons of the sulfur and the σ*(N–H) antibonding orbitals of both the N1–H
and -NH2 groups. Moreover, the computed lpS→ σ*(N–H) values are similar, suggesting
similar strength for both C=S···H–N intermolecular hydrogen bonds.
4- Conclusions
The molecular and crystal structures of the novel species 1-(2-chlorobenzoyl)thiourea
are strongly determined by intramolecular and intermolecular hydrogen bond. The formation
of an intramolecular C=O···H–N2 hydrogen bond is promoted by an lpO→ σ*(N2–H)
hyperconjugative interaction that favors the adoption of the S conformation of the 1-acyl
thiourea group. Low frequency values observed in the vibrational spectra (infrared and
26

Raman) for the ν(C=O) (1684 cm–1) and νs(NH2) (3114 cm–1) stretching modes are clear
manifestations of this interaction.
The topological analysis clearly identify two different intermolecular N–H···S=C
hydrogen bonds forming pseudo eight-membered rings between adjacent molecules. The
NBO analysis allowed to characterize the hyperconjugative lpS→ σ*(N–H) remote
interaction as important factor of covalency for these bonds, respectively.
5- Acknowledgments
ACF and MFE are members of the Carrera del Investigador of CONICET (República
Argentina). The Argentine authors thank the Consejo Nacional de Investigaciones Científicas
y Técnicas (CONICET), the ANPCYT and the Facultad de Ciencias Exactas, Universidad
Nacional de La Plata for financial support.
6- Supplementary data. Atomic coordinates, equivalent isotropic displacement coefficients,
geometrical parameters and anisotropic displacement parameters are given in Tables S1-S3,
respectively. Tables S4 and S5 list the hydrogen bond geometrical parameters and torsion
angles, respectively. Figures S1 and S2 show the computed [B3LYP/6-311++G(d,p)]
molecular structure for the dimer and trimer aggregates, respectively.
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