Hydrogen Bonding Networks in Chiral Thiourea Organocatalysts: Evidence on the Importance of the Aminoindanol Moiety

Article abstract of DOI:10.1021/acs.cgd.6b00683

The crystal structures of four chiral thioureas, which are normally used as organocatalysts, are reported by the first time. Each compound is assembled in the crystal in a different way according to their chiral moiety in the thiourea skeleton, being depe

Full text of DOI:10.1021/acs.cgd.6b00683

Article
pubs.acs.org/crystal
Hydrogen Bonding Networks in Chiral Thiourea Organocatalysts:
Evidence on the Importance of the Aminoindanol Moiety
M. Concepcion Gimeno*,† and Raquel P. Herrera*,‡
́
†Departamento de Química Inorgan
́
ica. Instituto de Síntesis Química y Catal
Zaragoza. E-50009 Zaragoza, Aragon, Spain
‡Laboratorio de Organocatal
isis Asimetrica. Departamento de Química Organ
Homogenea (ISQCH), CSIC-Universidad de Zaragoza. E-50009 Zaragoza, Aragon
́ ́
isis Homogenea (ISQCH), CSIC-Universidad de
́
́
́
́
ica. Instituto de Síntesis Química y Catal
́
isis
́
́
, Spain
S
* Supporting Information
ABSTRACT: The crystal structures of four chiral thioureas, which
are normally used as organocatalysts, are reported by the first time.
Each compound is assembled in the crystal in a different way
according to their chiral moiety in the thiourea skeleton, being
dependent on the presence or the absence of the OH group in the
aminoindanol or aminoindane moiety, respectively. Thiourea 1, which
contains an aminoindane group, is assembled into a zigzag chain
linked via N−H···S hydrogen bonds. Thiourea 2, with an amino-
indanol and a phenyl group, interacts mainly through O−H···S and
N−H···S bonds in a very congested structure. Thiourea 3 disposes in a
zigzag chain mainly through S···O−H bonds and in further
superposed zigzag chains through N−H···S hydrogen bonds. The
compound 4 is coordinated in a coplanar organization via O···H−N
interactions, forming very tight dimers, which are further arranged in
chain of dimers through O−H···S interactions. The general trends in the patterns of packing of these four compounds are
compared to those commonly observed in the crystalline solids of other thiourea and urea structures. The different arrangements
adopted by our chiral thioureas in the solid state are rationalized and discussed in terms of molecular structure, remarking the
importance of the OH group in the aminoindanol scaffold in the determination of the preferred solid assembly. A comparison
correlating the crystal structures, specifically the interactions in the crystal network and the configuration adopted by the
thioureas, with the catalytic efficiency previously observed by the same structures, is included.
search for new hydrogen bond-based motifs. More important is
the fact that it is able to take advantage of this strong hydrogen
bond capacity to use these molecules as active hydrogen bond
catalysts.2 In this manner, we have centered part of our
investigation using thiourea building blocks to promote several
asymmetric organocatalytic reactions.16−21
However, in contrast to the most explored urea structures in
crystal engineering,22−24 crystalline solids of thiourea deriva-
tives have been so far less explored, but some systematic
crystallographic studies based on single crystals and powder X-
ray data have been performed,25−30 despite the fact that they
can also form relatively strong and directional hydrogen
bonding interactions.31 A proof of fact of their well-known
capacity as hydrogen bond donor, is their extensive use in
asymmetric organocatalysis as a powerful chiral catalyst.32−36
Therefore, the lack of background using thiourea scaffolds for
crystal design prompted us to study our own chiral thiourea
catalysts from a crystalline point of view and in order to see a
1. INTRODUCTION
With the main aim of designing and controlling new crystal
structures with appealing architectures, noncovalent interac-
tions have played a crucial role in the progress of supra-
molecular chemistry. This approach is still an active challenging
area of research. Although it is well-known that hydrogen bonds
are much weaker than covalent unions, in the past decade these
unions have become a key tool in crystal engineering1 and in
asymmetric catalysis,2 because of the possibility of forming
highly directional and strong associations, based on a
cooperative effect.3 Among all the molecules involved in this
field, ureas and thioureas have been the subject of extensive
studies in the design of new three-dimensional crystal
structures. Furthermore, ureas4−9 and thioureas10−14 have
been extensively used as anion binding groups in synthetic
receptors because of their ability to form strong hydrogen
bonding with a great variety of anions.
Although, at this point, the prediction of the exact crystal
structure of a given molecule remains as an elusive goal,15 the
capacity of (thio)ureas to form robust intermolecular
interactions in the solid state, allowing the control of the
crystal packing, has stimulated the growth of this field and the
Received: May 5, 2016
Revised: July 18, 2016
© XXXX American Chemical Society
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Figure 1. Thioureas 1−4 used in the comparative crystalline study.
possible correlation between the behavior in the solid state and
that observed in solution when they are used as organocatalysts.
We report the crystal structures of these four chiral thioureas
1−4 (Figure 1) derived from the aminoindane or aminoindanol
skeleton and bearing the bulky bis(trifluoromethyl)phenyl or a
simple phenyl group. Their crystalline structures are analyzed in
terms of the expected behavior observed by other thioureas or
ureas.
preferences afford the formation of straight chains formed in
ureas, with the molecules approaching each other through their
CO vector and to zigzag chains in thioureas because the
molecules approach obliquely in order to optimize the
electrostatic interactions between the NH protons and the
negative charge of the sulfur atom (Figure 2).
For comparative purposes, we have selected the results
achieved with these catalysts in the Friedel−Crafts alkylation
reaction between indole 5 and nitrostyrene 6 at low
temperature (Table 1),18 although the same tendency can be
observed in other reactions explored by us when these catalysts
have been used.16−21
Table 1. Thiourea-Catalyzed Friedel-Crafts Alkylation
a
Reaction
Figure 2. Normal spatial approach in (thio)ureas.
Taking this into account, we started studying the structure of
catalyst 1 with the aminoindane chiral group. Compound 1
crystallizes in the monoclinic system and P21 space group with
two independent molecules in the asymmetric unit, corre-
sponding to the 1R enantiomer. The conformational
disposition in both molecules is trans,trans. In these two
molecules the planes formed between the thiourea SCN2
moieties are situated almost perpendicular to each other, with
an angle of 98.2°, and the sulfur atom points out toward the
NH groups of the other thiourea molecule (Figure 3).
The structure corresponds with hydrogen-bonded chains
between the two NH proton donors and the S atom in other
adjacent thiourea molecule. In these layers, the S atom of
thiourea acts as a proton acceptor with bifurcated hydrogen
bonds with the NHs of the adjacent thiourea skeleton, which
act as proton donors, in a very organized network. This effect is
the most typical behavior observed in urea architectures due to
the most polar character of the CO bond compared with
CS bond and the corresponding more favorable self-
association in urea structures.40 This behavior can be also
rationalized in terms of ab initio methods, which support
differences in energy for the N−H···S compared with N−H···O
interaction in the chain dimers, being weaker in thioureas than
in ureas.41,42
catalyst
time (h)
yield (%)
ee (%)
1
2
3
4
120
120
120
72
24
12
28
40
racemic
racemic
10
82
a
Experimental conditions: To a mixture of catalysts 1−4 (0.02 mmol),
nitroalkene 6 (0.1 mmol) in CH2Cl2 (500 μL) in a test tube at room
temperature was added indole 5 (0.15 mmol). After the reaction time,
compound 7 was isolated by flash chromatography.
To the best of our knowledge, only two precedent
characterizations of enantiomerically pure thioureas by X-ray
diffraction studies have been carried out.37,38 The present study
represents the first correlation study between the crystal
structures of potential organocatalysts in the solid state,
supporting the outcome obtained in catalytic reactions and
complementing the architectonic chemistry observed so far in
the literature for these attractive structures. Moreover, this is
the first example where chiral thiourea crystals are analyzed
from a solid state engineering point of view.
2. RESULTS AND DISCUSSION
This spatial arrangement is persistent in the space and allows
a coplanar approach of the thiourea blocks in the plane defined
by each thiourea chain, being symmetric each two layers and
separated by a distance of about 3.8 Å between the two first
planes and 4.3 Å between the second and third plane.
Moreover, the aminoindane skeleton is shifting its relative
position each two layers in order to accommodate the chiral
part of the structure (see Figures 4 and 5).
Small differences have been described between ureas and
thioureas in crystal engineering networks. These come from the
differences between the oxygen and the sulfur atom in the
system, and whereas the thiocarbonyl group is a weaker
hydrogen-bond acceptor than the carbonyl one, this property is
compensated by the strongest acidity of the NH donors in
thioureas.39 This leads to significant variations between these
two molecules in their conformational behavior and hydrogen
bonding preferences. From an experimental point of view, these
According to this arrangement, there are two distinct
hydrogen bonds (Table 2), those between the two independent
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Figure 3. (a) Molecular structure of one molecule of thiourea 1. (b) Disposition of the two independent molecules with intermolecular contacts.
Table 2. Hydrogen Bond Parameters for Compound 1
D−H
H···A
D···A
∠(DHA)
0.76(3)
0.81(3)
0.81(3)
2.70(3)
2.58(3)
2.46(3)
3.436(3)
3.361(2)
3.257(2)
162(2) N4−H04···S1
162(2) N3−H03···S1
172(3) N2−H02···S2_$1
($1 = x − 1, y, z)
0.86(3)
2.67(3)
3.464(2)
155(2) N1−H01···S2_$1
($1 = x − 1, y, z)
interaction is observed each two groups. Surprisingly, the
distances from the NH to the S atom are different along the
chain polymer. In the dimers, belonging to the asymmetric unit,
the distance from the most acidic H atom is higher (2.70(3) Å)
than the distance to the less acidic H atom (2.58(3) Å).
However, in the symmetry translated molecules the distance
from the most acidic H atom is shorter (2.46(3) Å) than the
one with the less acidic H atom (2.67(3) Å).
Interestingly, this trans,trans disposition is in agreement with
the poor capacity of activation shown by this thiourea in
organocatalytic reactions. Since, as observed by us, the absence
of the OH group in its skeleton makes this structure a less
efficient catalyst than 4 (see entries 1 and 4, Table 1).16−19,21
Computational calculations reported by us demonstrated the
participation of the OH in the activation of the nitroalkene
(Figure 6) and its important role in the Friedel−Crafts
alkylation mechanism, justifying the lack of reactivity observed
when catalyst 1 is used.19
Figure 4. Zigzag chain union with a trans,trans arrangement.
molecules with values N1−H03···S1 of 2.58(3) and N1−H04···
S1 of 2.70(3) Å, and angles close to the linearity, 162(2)°, and
those related by symmetry with the next layer, N1−H01··· S2_
$1 2.67(3) Å, angle of 155(2)° and N2−H02···S2_$1 2.46(3)
Å, angle of 172(3)° ($1 = x-1, y, z).
In contrast to the straight chains shown in ureas along the
CO vector, since the electron density is found around the
axial position of the CO bond, in thiourea 1 it is possible to
observe the preferential zigzag movement43 that the oblique
CS group is described in the space. This oblique contact
occurs in order to optimize the electrostatic interactions
between the NH protons and the negative charge over the S
atom, disposed in an equatorial belt around the S atom.44
Additionally, close contacts (∼2.65 Å) within the layers exist
between a F atom of the CF3 group with the ortho-H (C−H···
FCF2) by the same side of two consecutive aryl rings, and this
Thiourea 2 contains the aminoindanol group in a cis,trans
arrangement related to the NH groups and, instead of the more
bulky and electron-withdrawing CF3 groups, there are hydrogen
atoms. The crystal structure of thiourea 2 is shown in Figure 7.
Figure 5. Zigzag movement observed for chiral thiourea 1.
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the aromatic ring supporting, at the same time, the almost lack
of reactivity also observed with this catalyst (entry 2, Table 1).
Moreover, the nitroalkene 5 prefers to be coordinated through
a bidentate coordination, as pioneering observed by Etter and
co-workers,46 providing a more rigid TS among the three
species involved in the process,19 which in this case, with
thiourea 2, is less probable. This fact would also support the
lack of enantiomeric excess when this catalyst is used.
Thiourea 3 contains the aminoindanol group in a trans,trans
disposition related to the NH groups and the bulky 3,5-
(CF3)2C6H3 moiety. Compound 3 crystallizes with only one
molecule in the asymmetric unit in the orthorhombic chiral
P212121 group. The structure corresponds with the 1R,2R
enantiomer. It can be observed that one of the NH groups is
slightly turned over the perpendicularity. This distorted
trans,trans disposition, also makes difficult the formation of
hydrogen bonds between these two NH groups and the sulfur
atom. The crystal structure of thiourea 3 is shown in Figure 10.
This twisted trans,trans arrangement found in 3 supports the
lack of reactivity observed with this catalytic structure in our
reactions (entry 3, Table 1), since this disposition of the NHs
would be difficult with the right bidentate activation of the
electrophile in our Michael addition reactions, as previously
described,16−21,47 and more entropic energy would be required
to order the catalyst in the TS.45 Moreover, the trans-
disposition of the OH group in the aminoindanol moiety
would not allow the right activation of the nitroalkene as
previously supported with computation calculations (Figure
11)19 and as above-mentioned in Figure 6.
Interestingly, we did not observe the formation of the
interaction between both NHs of the thiourea with the S atom
of the consecutive one in 3. In contrast, the layers are formed
by coordination of the OH group with the less acidic NH of
other thiourea (H−O···H−N; 2.15(5) Å) by the same side.
Therefore, it is possible to observe the formation of a chain
with the zigzag shape with the molecules perfectly orientated in
totally coplanar organization (Figure 12). In this arrangement, a
short H···π interaction to the centroid of the phenyl ring of the
aminoindanol moiety of 2.67 Å is observed.
Figure 6. Crucial role of the cis OH group in the aminoindanol
moiety.
It crystallizes with only one molecule per asymmetric unit in
the monoclinic chiral P21 space group. The structure
corresponds with the 1R,2S enantiomer. The protons of the
nitrogen atoms point out to opposite direction, cis,trans
disposition, which is not the ideal situation for an efficient
hydrogen bond donor catalyst since this avoids the right
bidentate coordination of the electrophiles (as shown in Figure
6).19,45 There are two main short contacts between adjacent
molecules and correspond to the OH···S hydrogen bond of
2.55(2) Å and S···HN bond of 2.56(2) Å, with angles very close
to linearity of 173.6(19) and 160.1(16)°, respectively (see
Table 3). This is a noncommon disposition in thiourea
molecules, because the dimer formation takes place through
shoulder-to-shoulder NH···S hydrogen bonds. The presence of
the OH group in the aminoindanol moiety is crucial for this
different pattern.
The packing diagram of 2 shows all the molecules located in
a parallel fashion and connected by the main OH···S and NH···
S hydrogen bonds and other secondary bonds between several
protons with the nitrogen or the carbon atoms of the aromatic
rings, thus, forming a three-dimensional network (Figure 8).
Schreiner and co-workers reported that the strength of the
interaction also depended on the rigidity of the catalyst, which
at the same time is related with the entropy of the catalyst to be
ordered for the suitable interaction with the electrophile.45
Moreover, it was proposed that the presence of an electron-
withdrawing group in the para-position of the aromatic ring
provides a most positive polarization of the hydrogen atoms in
the ortho-position allowing an attractive interaction between the
H···S (Figure 9). This interaction can influence on the rotation
of the phenyl group, avoiding it and consequently, favoring the
catalysis.
Additionally, there are also short intermolecular hydrogen
bonds between the sulfur atom of the thiourea and the proton
of the OH group, O1−H0···S1 2.42(5) Å (Table 4), which
affords the formation of another zigzag chain (Figure 13a).
These two zigzag chains are superposed originating a three-
dimensional array as shown in Figure 13b.
Interestingly, the cis,trans configuration found in the crystal
structure of thiourea 2 is consistent with the lack of the CF3
groups in the aromatic ring, which would allow the rotation of
The structure of thiourea 4, with the OH group in the cis
relative position is displayed in Figure 14a. It crystallizes with
Figure 7. (a) Molecular structure of thiourea 2 cis,trans. (b) Dimer formation through OH···S and NH···S hydrogen bonds.
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Table 3. Hydrogen Bond Parameters for Compound 2
D−H
H···A
D···A
∠(DHA)
0.822(19)
0.82(2)
2.56(2)
2.55(2)
3.3432(15)
3.3667(14)
160.1(16)
173.6(19)
N1−H01···S1_$1 ($1 = −x + 1, y + 1/2, −z)
O1−H0···S1_$2 ($2 = −x + 1, y − 1/2, −z)
Figure 11. Nonappropriate coordination of the nitro group.
Figure 8. Packing diagram of thiourea 2 showing the hydrogen bond
network.
Figure 9. Attractive interaction avoiding the rotation of the phenyl
groups.
Figure 12. Arrangement of thiourea 3 through short H−O···H−N
bonds and H···π interaction.
only one molecule in the asymmetric unit in the orthorhombic
chiral P21212 group and with half molecule of dichloromethane.
The structure corresponds with the 1S,2R enantiomer. It is
interesting to observe three different hydrogen bonding types.
The first one is confined in the very congested union between
two faced thioureas and formed by OH coordination with two
NH of the facing thiourea (Figure 14b). The distance between
the OH and the most acidic NH is 2.35(3) Å, while the less
acidic one is placed at 2.10(3) Å. This conformational
preference is rare since the bulkiness of the organic substituents
is expected to govern the arrangement of the final structure
giving rise to a less hindered coordination.26
Table 4. Hydrogen Bond Parameters in Thiourea 3
D−H
H···A
D···A
∠(DHA)
0.86(5)
0.76(5)
2.42(5)
2.15(5)
3.206(4)
2.897(6)
153(5)
172(6)
O1−H0···S1_$1
N2−H2···O1_$2
between the two bis(trifluoromethyl)phenyl groups, with a
short distance of 3.514 Å, and between the phenyl rings of the
two aminoindanol moieties, with a distance of 3.561 Å. This
couple of molecules interact with the OH groups of other
adjacent couple of thiourea molecules through the sulfur atom,
In order to explain this uncommon association within both
thiourea molecules, we could invoke a favorable π−π staking
Figure 10. Molecular structure of thiourea 3 and formation of dimers through OH···S hydrogen bonds.
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Figure 13. (a) Formation of other zigzag chain through S···OH bonds. (b) Superposed zigzag chains.
Figure 14. (a) Molecular structure of thiourea 4. (b) Dimer formation of thiourea 4.
O−H···S 2.56(4) Å and some short F···H contacts of 2.610 Å,
forming a chain of thiourea dimers (Figure 15).
disposition of both NHs are in agreement with our mechanistic
hypothesis regarding the bifunctional character played by this
structure in the Michael reactions depicted in Figure 16.16−19,21
This crystal structure supports the high capacity of this catalyst
to promote different reactions in comparison with the other
three structures studied.48
Consequently, the pattern in which thiourea 4 is packed is
different to those observed in crystalline solids of previously
published thioureas.24−28 Additionally, this packing is also
different from those found with the other thioureas 1−3
described here. The difference mainly relies in the strong
hydrogen bonding between the hydroxyl group of the
aminoindanol and the NHs protons of the thiourea. These
contacts are specially relevant in the mode of action of these
hydrogen bond donor catalysts, since it makes possible the
trans,trans disposition of the NH groups for the right activation
of the substrates in the catalytic processes (Figure 6 and 16).
Hydrogen bond parameters for compound 4 are summarized in
Table 5.
These interactions would be in agreement with a recent
mechanistic proposal reported by us in which an external
Brønsted acid would activate our thiourea catalyst enhancing
the reactivity and the enantioselection of the catalytic system.18
Additionally, the planarity of the aminoindanol moiety and the
orientation of the OH group joined to the directional
FT-IR spectroscopy analysis is one of most widely used
techniques to support possible hydrogen bond interactions
between at least two organic molecules, providing information
about hydrogen bonds in the solid state.28,49 Functional groups
OH and NH, participating or not in hydrogen bonding, can be
monitored by IR spectroscopy. The IR spectra for thioureas 1−
4 are collected in the Supporting Information of this article and
the main bands in Table 6. It is remarkable that the frequency
values of N−H and O−H stretching vibration modes are
significantly lower than those corresponding to nonassociated
Figure 15. Formation of chains with thiourea dimers 4.
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Table 6. Main IR Bands for Thioureas 1−4 (cm−1)
υ(CS) and
thiourea conformation
υ(O−H)
υ(N−H)
3222(br)
υ(CN)
1
2
trans,trans
cis,trans
1125−1560(s)
1127−1590(s)
3401(s)
3373(s)
3401(br),
3212(br)
3
4
distorted
3313(br),
3231(br)
1122−1560(s)
1130−1530(s)
trans,trans
trans,trans
3100(br) 3238(br)
thiourea is compared. The OH group present in the
aminoindanol skeleton has been also found crucial, with the
cis configuration, for the success of the catalytic examples
previously studied.48 Different modes of coordination have
been reported through hydrogen bonds which exhibit different
connectivity in the solid state. In this sense, H−O···H−N, O−
H···S, or N−H···S have been identified as the main
intermolecular hydrogen bond interactions. These bonds
successfully assemble the molecules in the crystal structure.
The interactions in the crystal network seem to be in
agreement with the catalytic behavior previously observed by
the same structures in Michael addition reactions. The
differences and similarities with other model systems containing
a thiourea or urea skeleton have been also discussed. Our study
extends and complements the works so far reported concerning
thioureas, since this is the first work focused on chiral
organocatalytic structures. These results could open a new
interesting line of research related to the study of other chiral
thiourea and urea scaffolds, which has not been previously
considered in the literature. Moreover, this contribution could
become an important precedent for further researches.
Figure 16. Bifunctional mode of action by thiourea 4.
N−H and O−H groups in thioureas. In all the thioureas several
bands appear in the range 1125−1550 cm−1 and they
correspond to υ(CS) and υ(C−N) vibrations modes. The
spectrum of thiourea 1 exhibits a broad band at 3222 cm−1,
which is in agreement with the presence of N−Hs coordinated
in the solid state, as we have found in the solid state structure
with strong S···HN interactions. Thioureas 2 and 3 showed two
closely N−H stretching bands at 3401 and 3212 cm−1 and 3313
and 3231 cm−1, respectively, as a consequence of the rotamers
with NH in cis,trans (2) or distorted trans,trans (3), as shown
above for these crystal structures.50 The absorptions related
with the OH···S coordination are also observed in thioureas 2
and 3 at 3401 cm−1 (a narrow band) and at 3373 cm−1 (a
narrow band), respectively. For thiourea 4, the υ(N−H) band
appears at 3238 cm−1, indicating a higher degree of hydrogen
bonding, in a similar order to thiourea 1, since with both N−H
in trans a major association is expected. Additionally, in
thiourea 4, the absorption related with the OH···S coordination
is also observed around 3100 cm−1 (a broad band).51 The
narrow bands in 2 and 3 are related with a less associated OH
group in the packing of these molecules in sharp contrast with
the broad band found in 4. All these data also support the
hydrogen bonds observed in the crystal structures.
EXPERIMENTAL SECTION
■
General Experimental Methods and Instrumentation.
Purification of reaction products was carried out by flash
chromatography using silical gel (0.063−0.200 mm). Analytical thin
layer chromatography was performed on 0.25 mm silical gel 60-F
plates. ESI ionization method and mass analyzer type MicroTof-Q
were used for the ESI measurements. H and 13C{1H}-APT NMR
1
were recorded at room temperature on a Bruker Avance 400
spectrometer (1H, 400 MHz; 13C, 100.6 MHz) in CDCl3 as solvent.
Chemical shifts were reported in the δ scale relative to residual CHCl3
1
(7.28 ppm) for H NMR and to the central line of CDCl3 (77 ppm)
for 13C NMR. The IR spectra were recorded with two different
spectrometers, one with Fourier transform, a Fourier Nicolet Avatar
360 FI-IR, and a PerkinElmer FT-IR spectrometer equipped with a
universal ATR sampling accessory.
General Procedures. Thioureas 1, 3, and 4 have been prepared as
previously described by us.17 Thiourea 2 has been synthesized by a
similar procedure.
General Procedure for the Preparation of Thiourea 2. To a stirred
solution of phenyl isothiocyanate (1.1 mmol) in CH2Cl2 (5 mL),
commercially available chiral (1R,2S)-cis-1-amino-2-indanol (1 mmol)
was added in one portion. After stirring the resulting solution at room
temperature overnight, the solvent was evaporated under reduced
pressure and the product purified by flash chromatography (SiO2,
hexane/EtOAc 7:3). Thiourea 2 was obtained as a white solid in 89%
CONCLUSIONS
■
The crystal structures of four chiral thiourea organocatalysts are
described by the first time. This study illustrates different
packing modes determined by the presence or the absence of
the OH group and its relative configuration in the amino-
indanol skeleton. Additionally, the importance of the presence
of a bulkiest substituent in the other amine group of the
1
yield. H NMR (CDCl3) δ (ppm): 8.14 (br s, 1H), 7.45−7.15 (m,
Table 5. Hydrogen Bond Parameters in Thiourea 4
D−H
H···A
D···A
∠(DHA)
0.73(3)
0.81(3)
0.80(4)
2.10(3)
2.35(3)
2.56(4)
2.840(2)
3.101(2)
3.2980(16)
164(3)
150(3)
162(3)
N2−H2···O1_$1 ($1 = −x, −y + 1, z)
N1−H1···O1_$1 ($1 = −x, −y + 1, z)
O1−H0···S1_$2 ($2 = −x + 1/2, y − 1/2, −z + 1)
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Table 7. X-ray Data for Compounds 1−4
compound
formula
1
2
3
4·1/2CH2Cl2
C18H14F6N2S
404.37
C16H16N2OS
284.37
C18H14F6N2OS
420.37
C18.50H15ClF6N2OS
462.83
Mr
habit
colorless prism
0.38 × 0.34 × 0.26
monoclinic
P21
colorless prism
0.44 × 0.24 × 0.20
monoclinic
P21
colorless plate
0.41 × 0.20 × 0.05
orthorhombic
P212121
colorless prism
0.38 × 0.36 × 0.30
orthorhombic
P21212
crystal size (mm)
crystal system
space group
cell constants:
a (Å)
7.9961(2)
16.3151(4)
13.8271(3)
90
10.612(2)
6.1475(12)
10.714(2)
90
4.7304(8)
11.420(9)
32.857(16)
90
10.4055(4)
b (Å)
12.4576(5)
c (Å)
14.7926(6)
α (deg)
β (deg)
γ (deg)
V (Å3)
90
96.032(3)
90
96.76(3)
90
90
90
90
90
1793.86(8)
4
694.1(2)
2
4141.9(14)
4
1917.53(13)
4
Z
Dx (mg m−3
)
1.497
1.361
0.230
300
1.573
0.254
856
1.603
0.378
940
μ (mm−1
F(000)
T (°C)
2θmax
)
0.244
824
−173
51
−173
51
−173
51
−173
51
No. of refl.:
measured
14146
6430
16352
2574
4191
20202
3584
independent
2931
transmissions
Rint
0.9129−0.9392
0.0278
600
0.9056−0.9555
0.0268
245
0.9029−0.9874
0.0509
309
0.8696−0.8950
0.0165
327
parameters
restraints
1
1
0
0
goodness of fit on F2
wR(F2, all refl.)
R(I > 2σ(I))
1.027
1.059
1.008
1.072
0.0761
0.0353
0.238
0.0513
0.0219
0.169
0.0901
0.0623
0.251
0.0794
0.0299
0.469
max. Δρ (e Å−3
)
9H), 6.77 (d, J = 7.9 Hz, 1H), 5.98 (dd, J = 7.8, 5.2 Hz, 1H), 4.83−
4.75 (m, 1H), 3.20 (dd, J = 16.7, 5.3 Hz, 1H), 2.90 (dd, J = 16.7, 1.7
Hz, 1H), 2.32 (br s, 1H). 13C-APT NMR (CDCl3) δ (ppm): 180.7
(1C), 140.0 (1C), 139.9 (1C), 136.3 (1C), 130.0 (2C), 128.4 (1C),
127.2 (1C), 126.9 (1C), 125.4 (1C), 124.7 (2C), 124.6 (1C), 73.4
(1C), 63.2 (1C), 39.7 (1C). HRMS (ESI+) calcd C16H16N2NaOS,
307.0876; found, 307.0880 [M + Na].
Accession Codes
CCDC 1478178−1478181 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge
CB2 1EZ, U.K.; fax: +44 1223 336033.
Crystal Structure Determinations. Crystals for thioureas 1−4 have
been obtained by slow diffusion of n-hexane into a dichloromethane
solution. Data were recorded with an APEX-II CCD for compound 4
or an Xcalibur diffractometer for compounds 1, 2, and 3. The crystals
were mounted in inert oil on glass fibers and transferred to the cold
gas stream of the diffractometer. Data were collected using
monochromated Mo Kα radiation (λ = 0.71073 Å) in ω-scans.
Absorption corrections based on multiples cans were applied by using
the SADABS program (4)52 or spherical harmonics implemented in
SCALE3 ABSPACK scaling algorithm (1−3).53 The structures were
solved by direct methods and refined on F2 by using the SHELXL-97
program.54 All nonhydrogen atoms were refined anisotropically. All
hydrogen atoms were located in the Fourier map. The crystallographic
details are summarized in Table 7.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: gimeno@unizar.es.
*E-mail: raquelph@unizar.es.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
́
Authors thank the Ministerio de Economia y Competitividad
(MINECO/FEDER CTQ2013-48635-C2-1-P), the High
Council of Scientific Investigation (CSIC; PIE-201580I010),
́
and Gobierno de Aragon-Fondo Social Europeo (E77 and
ASSOCIATED CONTENT
E104) for financial support of our research.
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.cgd.6b00683.
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DOI: 10.1021/acs.cgd.6b00683
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