Hydrogen bonding interactions with the thiocarbonyl π-system

Article abstract of DOI:10.1039/c0ce00680g

Hydrogen bonding interactions with the π-system of thiocarbonyls are evident in the X-ray crystal structures of a range of thiourea derivatives and from an analysis of the CSD.

Full text of DOI:10.1039/c0ce00680g

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PAPER
Hydrogen bonding interactions with the thiocarbonyl p-system†
Joseph T. Lenthall, Jonathan A. Foster, Kirsty M. Anderson, Michael R. Probert, Judith A. K. Howard
and Jonathan W. Steed*
Received 28th September 2010, Accepted 29th November 2010
DOI: 10.1039/c0ce00680g
Hydrogen bonding interactions with the p-system of thiocarbonyls are evident in the X-ray crystal
structures of a range of thiourea derivatives and from an analysis of the CSD.
Introduction
most common in thiourea derivatives. The hydrogen bonding
motifs that arise from these preferences are chains formed by the
tape motif of the syn-conformation, and centrosymmetric dimers
formed the anti-conformation.
Supramolecular interactions involving p-electron density are
1
a fundamental class of supramolecular synthon with p–p
stacking and CH/p interactions being perhaps the most well
known examples. The OH/p and NH/p interactions are also
now well recognised in aromatic systems.
The difference between hydrogen bonding to carbonyl and
thiocarbonyl bonds has been only sparsely discussed. One
important study into the differences of hydrogen bonding to
carbonyl and thiocarbonyl fragments utilized the Cambridge
Structural Database (CSD) to compare the metrics of crystal
2–6
7
–10
Supramolecular
interactions involving carbonyl and thiocarbonyl X]C (X ¼ O,
S) bonding p-electron density are less well understood and
generally not used as reliable synthons. Despite this comparative
scarcity one of the earliest examples of the interaction between
hydrogen bonds and the p-electrons of carbonyls occurs in the
18
structures from the literature. It was shown that hydrogen
bonds to C]S bonds are weaker than to C]O bonds, and that
C]S fragments are more likely to accept more than one
hydrogen bond donor. Interestingly, in the orientation distri-
bution of H-bond donors it is observed that the distribution out
of the plane of the lone pairs is more diffuse for thiocarbonyls,
11–14
well-known crystal structure of b-urea.
The urea oxygen atom
is involved in four hydrogen bonds: two through the nonbonding
lone pairs on the oxygen atom and two through the p-electrons of
the carbonyl double bond. The p-bonded hydrogen bond donors
are situated out of the O]C–N plane and the angle to the
ꢀ
ꢀ
extending from the ideal 0 to a plane/H angle of 70 , whereas
interactions with the carbonyl bond tend to occur within the
ꢀ
carbonyl C]O bond of 106 is more acute than conventional
ꢀ
range of 0 to 20 . Within the lone pair plane, the hydrogen
hydrogen bonding to the oxygen lone pairs. The presence of four
hydrogen bond acidic NH protons and only one carbonyl
acceptor in urea means that every possible potential hydrogen
bond acceptor is involved in the structure. The situation is the
same in the analogous thiourea which displays several poly-
bonding is more directional than in thiocarbonyl bonds.
Crucially thiocarbonyl groups only act as effective hydrogen
bond acceptors if they are attached to groups they delocalise the
double bond electron density, as is the case in thioureas.
15,16
morphs,
however four hydrogen bonds are consistently
observed in each structure: two bonded to the lone pairs and two
others situated out of the S]C–N plane. The angle between the
thiocarbonyl bond and the two out of plane hydrogen atoms is
ꢀ
close to 90 in all forms.
Urea derivatives display different hydrogen bonding patterns
to thiourea derivatives due to differing conformational prefer-
ences arising from the differing availability of the sulfur and
oxygen atoms as hydrogen bond acceptors, and the different
X]C bond lengths. The syn- and anti-conformations of disub-
17
stituted ureas are shown in Fig. 1. While the syn-conformation
is most common in urea derivatives, the anti-conformation is
Chemistry Department, University of Durham, South Road, Durham, UK.
E-mail: jon.steed@durham.ac.uk; Fax: +44 (0)191 384 4737; Tel: +44
Fig. 1 syn and anti conformations adopted by disubstituted urea and
thiourea derivatives in the solid-state. The syn-tape hydrogen bonding
motif is common for urea derivatives, whereas the anti-centrosymmetric
(0)191 334 2085
†
CCDC reference numbers 795070–795075. For crystallographic data in
17
CIF or other electronic format see DOI: 10.1039/c0ce00680g
202 | CrystEngComm, 2011, 13, 3202–3212
dimer formation is common for thiourea derivatives.
3
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Some work has been carried out on the electron density of the
Results and discussion
19
lone pairs on the sulfur atom in a thioureido group.
Crystal structures
Bogdanovi ꢀc and co-workers identified that the sulfur atom in the
crystal structure of salicylaldehyde thiosemicarbazone has three
different hydrogen bonds to it, Fig. 2. One hydrogen bond is
from an NH of a thioureido group of another molecule of sali-
cylaldehyde thiosemicarbazone in a centrosymmetric dimer
fashion based on H(2N)/S(1), while there is hydrogen bonding
from an NH from another molecule, H(3A)/S(1). Both of these
interactions are in the thioureido plane. There is also a weak C–H
donation from a third molecule, which is out of the lone pair
plane. This latter interaction is a relatively long hydrogen bond
Compounds 2–6 are all readily prepared from reaction of
a diamine with an isothiocyanate in solution. Compounds 3–6
have been reported previously within the context of a study on
21
anion complexation by their ruthenium(II) derivatives. 1-
(
2-Amino-phenylene)-3-methyl-thiourea (1) and 1-(2-amino-
phenylene)-3-tert-butyl-thiourea (2) were synthesised as part of
this work (see Experimental section). We also attempted the
22,23
preparation of all six compounds mechanochemically
by
grinding either the neat solid or liquid starting materials in the
appropriate stoichiometric ratio in a Retsch MM200 ball mill.
Mechanochemistry has proved effective previously in amine–
ꢁ
with H(7)/S(1) distance of 3.008(8) A and a C(7)–H(7)/S(1)
ꢀ
angle of 124.64(7) . The final NH group, H(3B), hydrogen bonds
to O(1).
24
isocyanate reactions. In the case of compounds 2 and 6 the
A survey of the CSD found that 495 out of a total of 835 N–
H hydrogen bond interactions to the thioureido group in its
crystal structures exist as part of centrosymmetric dimers. These
dimers were compared to 3630 more general hydrogen bonding
interactions to thioureido functional groups, D–H/S]C
starting materials failed to react. Compounds 3 and 5 were
successfully prepared mechanochemically. Mechanochemistry
also proved to be the only effective way to isolate compound 1.
The slower kinetics of the mechanochemical reaction proved
effective at producing the monosubstituted product. In the case
of the isopropyl analogue a mixture of the monosubstituted
product and disubstituted 5 was produced, however this con-
verted to 5 upon recrystallisation.
(
D ¼ C, O, N). For the dimers, the average C]S/H bond
ꢀ
angle is in the region of 110 to 115 , whereas a wider distribu-
tion is observed for the non-dimer interactions, with an average
ꢀ
in the region of 80–100 . A lack of directionality in C]S/H
bonding is attributed to the torus of the lone pair electrons
The X-ray crystal structures of 1–6 were determined in order to
examine the distribution of hydrogen bonding involving the
thiourea groups. The X-ray crystal structures of 1 and 2, which,
like thiourea itself, are rich in hydrogen bond donor NH groups,
are shown in Fig. 3.
around the sulfur atom being equally polarisable in or out of the
19
plane.
In the present paper we present the structures of six new
thiourea derivatives bearing multiple NH hydrogen bond donor
groups. Steric hindrance of the thiourea groups in these types of
system is a significant factor in the availability of the hydrogen
20
bond donor and acceptor groups. We correlate this structural
data with data obtained from the CSD to show that the thio-
carbonyl group in thiourea derivatives acts as an effective
hydrogen bond acceptor via the p-electron density. The inci-
dence and metrics of the thiocarbonyl–p hydrogen bond inter-
action are presented.
For both compounds the molecular bond lengths and angles
are within expected ranges. Centrosymmetric dimer formation
through hydrogen bonded thiourea groups is common for
1
5,17
thioureas
and is observed in 2 for S(1) and H(2A), Fig. 3b.
ꢁ
The short H/S contact of 2.53 A, the obtuse C]S/H angle
ꢀ
of 107.3 , as well as the low torsional angle between N(2)–
ꢀ
Fig. 2 X-Ray crystal structure of salicylaldehyde thiosemicarbazone
C]S(1)/H(2A) of 11.1 with the thiocarbonyl bond are typical
of conventional hydrogen bonding with the nonbonding sulfur
19
displaying hydrogen bonding.
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Fig. 3 (a) X-Ray crystal structure of 1 showing the two independent molecules based on S(1) and S(2). The two conventional hydrogen bonding
interactions to S(2) are shown. The third interaction is orthogonal. The molecule based on S(1) exhibits a conventional hydrogen bond and an N–H/p
interaction. (b) X-Ray crystal structure of 2 showing one centrosymmetric dimer pair, while a second molecule hydrogen bonds through N–H into the p-
25,26
electron density of the thiocarbonyl bond. (c) Hirshfield surface
derived from the X-ray structure of 2 showing the three hydrogen bonding inter-
actions to the C]S bond as the three red regions.
3
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lone pair. However, in the structure of 2 one of the hydrogen
atoms on the primary amine, H(1B), is directed towards the
thiocarbonyl bond. In contrast to conventional hydrogen bonds,
an acute angle of the hydrogen atom donor with the thiocarbonyl
relatively long. In addition a third interaction is of the NH/p
type involving amine N(4)–H(4) and is positioned orthogonally
to the plane of the conventional hydrogen bonds. The N(4)/S(2)
ꢁ
distance of 3.453(2) A is considerably shorter than the conven-
ꢁ
ꢀ
bond of 83.6 is observed. This brings the hydrogen close to the
tional N(1)/S(2) distance, 3.6739(17) A. The molecule based on
centre of the double bond (the distance to the double bond
ꢁ
S(1) accepts hydrogen bonds from thiourea NH proton H(6) to
a lone pair, but from H(3A) via the thiocarbonyl p-electron
density. A more conventional approach to the remaining lone
centroid is 2.83, compared to an H/S distance of 2.80 A).
Furthermore, the torsional angle between the hydrogen, the
thiocarbonyl bond and the adjacent nitrogen atom (N–C]S/
pair is apparently sterically hindered by the aromatic ring,
2
ꢀ
H) is 100.1 ; well out of the conventional lone pair hydrogen
ꢀ
Fig. 3a. The structure of 1 also exhibits an unusual R
2
(9)
bonding plane (which has an ideal value of 0 ). The interaction is
hydrogen bonded ring involving the thiourea acceptor on one
molecule and the primary amine on the another. A final unusual
feature is one of the primary amine NH groups not engaged in
any significant hydrogen bonding interaction.
longer than the conventional hydrogen bond involving S(1) and
ꢁ
H(2A), with an H(1B)/S(1) distance of 2.79(2) A.
These parameters give a strong indication of interaction
between the hydrogen and the p-electron density of the double
bond, and thus evidence that p-electrons of thiocarbonyl bonds
act as hydrogen-bond acceptors, Fig. 4. The presence of three
strong hydrogen bonding interactions involving the thiourea
The structure of 1-methyl-3-[2-(3-methyl-thioureido)-ethyl]-
thiourea (3) was also determined by X-ray crystallography, and it
forms hydrogen bonds with very similar interactions to 2, Fig. 5.
A centrosymmetric dimer is present, as well as an interaction
with the p-electrons of the thiocarbonyl bond. Again, the two
different types of interaction display markedly different metrics,
25,26
group is confirmed by Hirshfield surface analysis
(Fig. 3c)
which shows the principal interactions in red. The two hydrogen
bonds that form the hydrogen bonded dimer are evident as the
two largest red regions of the surface, while the NH/p inter-
action is also clearly evident. Interestingly, there appears to be no
interaction with other molecules from the remaining two
hydrogen bond donor NH groups. The hydrogen atom from the
other thioureido NH group, N(3), appears to be sterically
hindered by the tertiary butyl group and aryl ring within the
same molecule, although there may be a weak N–H/p aromatic
interaction. The other free NH hydrogen atom is also turned
towards the aryl ring of another molecule, presumably from the
interaction of the other hydrogen on the amine with the thiourea
sulfur atom. Therefore the lack of hydrogen bonding in these two
NH groups is most likely attributable to the surrounding steric
bulk and dominance of the other hydrogen-bonding interactions.
Similarly the remaining thiourea lone pair is also sterically
hindered by the tert-butyl group.
ꢀ
in particular the C]S/H angle is 109.0 for the centrosym-
ꢀ
metric dimer pattern, whereas a C]S/H angle of 85.7 is found
for the hydrogen-bond donor that is out of the thioureido plane,
Tables 1 and 2.
The crystal structures of 4–6 similarly show a range of inter-
esting hydrogen bonding interactions including short contacts to
the C]S p-electron density in some, but not in all cases. The
crystal structure of 1-methyl-3-[2-(3-methyl-thioureido)-phenyl]-
thiourea (4) exhibits one thiourea group arranged in the anti
conformation, consistent with centrosymmetric dimer forma-
tion, while the other is arranged in the syn conformation.
However, in contrast to the structures of 2 and 3, compound 4
does not exhibit the centrosymmetric dimerisation typical of
The structure of 1 is more complicated than that of 2 and
0
exhibits two crystallographically independent molecules (Z ¼ 2,
ref. 27). The molecule based on S(2) exhibits two conventional
hydrogen bonds to the thiocarbonyl group with interactions
from thioamide and amine type NH donors approximately along
the lone pair directions, although one of these interactions is
Fig. 5 X-Ray crystal structure of 3 showing similar H-bond interactions
to those found in compound 2. The compound has crystallographic
twofold symmetry.
Fig. 4 Schematic diagram showing of hydrogen bonding to (thio)-
carbonyl (a) lone pairs and (b) p-electrons.
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Table 1 H-Bond metrics for the structures of 1, 2, and 3
Hydrogen atom
1
H(3A)–S(1)
2.62
84.5
H(6)–S(1)
2.81
117.9
H(2)–S(2)
2.57
112.4
H(4A)–S(2)
2.55
77.9
H(1B)–S(2)
2.90
115.5
ꢁ
S/H/A
C]S/H/
N–C]S/H/
S/N/A
C]S/N/
N–C]S/N/
ꢀ
ꢀ
ꢀ
104.4
22.8
22.1
97.9
171.9
ꢁ
3.3685(18)
81.1
96.4
3.4788(17)
108.3
26.3
3.3040(17)
117.4
13.5
3.453(2)
76.4
98.3
3.6739(17)
119.5
173.7
ꢀ
Hydrogen atom
2
H(1N)–S(1)
2.53
107.3
H(3N)–S1
2.79(2)
83.6
ꢁ
S/H/A
C]S/H/
N–C]S/H/
S/N/A
C]S/N/
N–C]S/N/
ꢀ
ꢀ
ꢀ
11.2
100.1
ꢁ
3.3551(11)
111.5
173.7
3.6130(15)
88.4
95.8
ꢀ
Hydrogen atom
3
H(1)–S1
2.49
109.0
11.2
3.353(3)
112.6
10.1
H(2)–S1
2.73
85.7
ꢁ
S/H/A
C]S/H/
N–C]S/H/
S/N/A
C]S/N/
N–C]S/N/
ꢀ
ꢀ
ꢀ
74.3
ꢁ
3.547(3)
87.1
68.4
ꢀ
thioureas. Each molecule, in fact, forms hydrogen bond dimers
of various types with three other molecules, Fig. 6.
other, H(3N), is more out of the plane with a torsional angle of
ꢀ
55 , Table 1. There is a significant difference in the C]S/H
The structure of 1-isopropyl-3-[2-(3-isopropyl-thioureido)-
phenyl]-thiourea (5) does exhibit the centrosymmetric dimer
synthon, H(2N)/S(1), Fig. 7. The hydrogen atom of the anti
thiourea group that is not involved in dimer formation, H(1N),
exhibits an intramolecular hydrogen-bond to the sulfur atom of
the thiourea group in the syn conformation, S(2). The hydrogen
atoms of this syn thiourea group bond to a sulfur atom of an
adjacent molecule, and while one, H(4N), is reasonably in the
angle observed for these two hydrogen bonds as well: the C]S/
ꢀ
H(3N) angle is 120 , whereas for the H atom that is out of the
ꢀ
plane the C]S/H(4N) angle is 88 .
The crystal structure of 1-methyl-3-[6-(3-methyl-thioureido)-
pyridin-2-yl]-thiourea (6) is shown in Fig. 8. Each thiourea group
forms centrosymmetric dimer involving H(2) and H(4), while the
remaining NH hydrogen atoms, H(1) and H(5), form intra-
molecular hydrogen bonds with the pyridyl nitrogen atom, N(3).
As each arm forms a centrosymmetric dimer with another
ꢀ
plane of the thiourea group with a torsional angle of 24 , the
Table 2 Hydrogen bonding metrics for 4 and 5
Hydrogen atom
4
H(3N)–S1
2.841(17)
125.4
H(4N)–S1
2.477(19)
117.0
H(2N)–S2
2.551(18)
113.0
H(1N)–S2
2.620(19)
124.0
ꢁ
S/H/A
C]S/H/
N–C]S/H/
S/N/A
C]S/N/
N–C]S/N/
ꢀ
ꢀ
ꢀ
36.1
15.1
60.3
91.6
ꢁ
3.5205(11)
133.1
149.3
3.2848(11)
122.1
16.1
3.3232(11)
107.3
62.0
3.3250(11)
131.4
95.8
ꢀ
Hydrogen atom
5
H(3N)–S1
2.52
88.3
H(4N)–S1
2.81
119.8
H(1N)–S2
2.38
81.1
H(2N)–S1
2.63
105.8
ꢁ
S/H/A
C]S/H/
N–C]S/H/
S/N/A
C]S/N/
N–C]S/N/
ꢀ
ꢀ
ꢀ
57.0
23.7
54.9
29.8
ꢁ
3.2840(17)
95.2
116.7
3.4948(18)
123.9
144.8
3.1082(15)
74.2
47.1
3.3949(16)
111.0
23.0
ꢀ
3
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Fig. 6 X-Ray crystal structure of 4 showing hydrogen bonded dimer formation in three different ways (a–c), and (d) the eight hydrogen bonding
interactions to a single molecule of 4 (red) from the three hydrogen bond dimers (green, blue and orange).
molecule, which in turn is forming a further dimer with the other
thiourea group, one-dimensional chains are formed. The pres-
ence of the additional pyridyl group in this compounds means
that there is no dearth of strong hydrogen bond acceptors,
however steric interactions between H(1) and H(5) cause the urea
groups to lie out of the plane of the pyridyl rings resulting in
inter-chain hydrogen bonds in which both sulfur atoms act as
bifurcated acceptors. While these additional interactions are not
to the S]C p electron density, they are out of the conventional
lone pair plane, highlighting the plasticity of the environment
around the sulfur acceptors.
from a torsional angle of zero degrees will reduce the lone pair
character of an interaction whilst increasing interaction with the
orthogonal p-electrons of the thiocarbonyl double bond.
For the case of NM–C]S/H–Q (NM ¼ any non-metal),
1623 hits were generated in the CSD constituting 3146 fragments,
while for NM–C]O/H–Q, a very large number of hits (38 179)
were generated. A scatter plot of the torsional angle distribution
displays typical behaviour for bonding to lone pairs with inter-
ꢀ
actions clustering around 0 and 180 .
However, a plot of the ratio of distances from the hydrogen to
carbon and sulfur atoms, H/C/H/S, Fig. 10 (orange line
denotes moving average), in thiocarbonyls shows that as the
torsional angle increases from zero, this ratio decreases in
magnitude. In other words, the hydrogen atom moves towards
the centre of the C]S bond as it moves out of the lone pair plane.
This behaviour is not observed in the C]O case, where
a constant average ratio is maintained throughout the torsional
range, Fig. 10.
CSD comparison of carbonyl and thiocarbonyl H-bond
interactions
To further investigate hydrogen bonding interactions with the
S]C p-electron density, a search of the CSD was undertaken to
explore hydrogen atoms bonded to good hydrogen bond donors
Q (Q ¼ N, O) that were bonded to hydrogen atoms within the
sum of the van der Waals radii of the acceptor of both thio-
carbonyl and carbonyl moieties (Fig. 9). A comparative study
was undertaken to investigate the torsional angle from the
hydrogen through the C]X bond (X ¼ O, S) and to an adjacent
atom. It is expected that interactions with the carbonyl or thio-
carbonyl lone pair will be in the plane of S–C–N fragment since
Further evidence is given by the distribution of the hydrogen
atoms about the thiocarbonyl bond. A distribution plot of
hydrogen bond donors about the X]C–N fragment (for X]S, O)
for all entries in the CSD with Q–H/X]C–N contacts was
28
generated using ISOSTAR. It is clear that the hydrogen bond
donation to the lone pairs is the dominant form of hydrogen
bonding to both of these fragments. However, if the search is
2
ꢀ
the S and O atoms are sp hybridised. Therefore deviation away
limitedtoatorsionalanglerangeof60to120 fortheH/X]C–N,
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Fig. 9 Schematic showing the H/C and H/X bond distances. The
ratio H/C/H/X indicates the relative position of the hydrogen atom to
the C]X bond, so that a decrease in the ratio is indicative of the
hydrogen atom moving closer to the carbon atom.
bond were also found. For the carbonyl case, the maximum donor
ꢁ
atom (Q) density was found at a distance of 2.9 A from the oxygen
ꢀ
atom and at an angle of 135 to the carbonyl bond. The maximum
density of the donor atom Q was found to be somewhat further
from the acceptor S atom of the thiocarbonyl than in the carbonyl
ꢀ
ꢁ
case at a distanceof 3.8 A, but at anangle of 89 to the thiocarbonyl
bond.
As can be observed from the contour plots, there is a striking
difference in the distribution of H-bond donors to the two bonds
within this torsional angle range. The examples reported in the
present work (1, 2 and 3) lie close to the carbon atom in the most
ꢀ
ꢀ
populated (blue) region with a C]S/N angles of 81.1 , 88.4
ꢀ
and 87.1 and S/N distances of 3.3685(18), 3.6130(15) and
ꢁ
.547(3) A, for 1, 2 and 3, respectively. They also possess a very
Fig. 7 X-Ray crystal structure of 5 showing hydrogen bonding inter-
3
actions.
similar angle to the thiocarbonyl bond as the maximum donor
density, with a slightly shorter S/N distance.
a large difference in the distribution of hydrogen bond donors
around the central X]C–N fragmentisobserved. Contour plots of
these distributions are shown in Fig. 11. For the carbonyl case, the
The metrics for the general carbonyl and thiocarbonyl cases
are summarized in Table 3. It can be seen that the H-bond
distance to carbonyls is generally stronger than to the thio-
ꢀ
ꢁ
distributioniscenteredatanangleof135 tothecarbonyl bondand
ꢀ
carbonyl bonds with X/H distances of 1.90 and 2.63 A,
respectively. While for carbonyls the bonding to hydrogen atoms
with an elongated ‘tail’ down to 180 to the bond. The distance
from the oxygen atom to the area most densely populated by donor
ꢁ
atoms is the region of 3.0 A. In contrast, the thiocarbonyl distri-
is relatively weakened in the cases where the torsional angle is
ꢀ
ꢁ
between 60 and 120 from the general case (1.90 to 2.06 A),
ꢀ
bution is more spherical and centered at 95 to the thiocarbonyl
a slightly stronger interaction is observed for examples at
ꢀ
ꢁ
bond, withanS–Qdistanceintheregionof4.0A. Thedistancesand
torsional angles between 60 and 120 (2.63 to 2.59 A). It is also
possible to see that for both carbonyl and thiocarbonyl general
ꢁ
angles from the maximum density of the donor atoms to the double
Fig. 8 X-Ray crystal structure of 6 showing hydrogen bonding interactions. Hydrogen bond distances: N(1)/N(3) 2.702(4), N(5)/N(3) 2.715(4),
0
00
0
00
ꢁ
N(5)/S(2) 3.367(3), N(1)/S(1) 3.380(3), N(4)/S(2) 3.434(3), and N(2)/S(1) 3.417(3) A.
3
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Fig. 10 Graphs of torsional angle vs. ratio of H/C and H/X distance in hydrogen bonding to C]X (X ¼ O, S). While for the carbonyl bond (X]O)
there is no variation in this ratio over the torsional angle range, there is a significant reduction in H–C/H–S for the thiocarbonyl range around 90
and ꢁ90ꢀ.
ꢀ
ꢀ
cases the C]X/H bond angle is similar at 117 and 115 for the
carbonyl and thiocarbonyl bonds respectively. However, at high
torsional angles, the angle between the H atom and the carbonyl
involved in this type of hydrogen bonding than is suggested by
Bogdanovi ꢀc and coworkers.
19
Limiting the search to hydrogen contacts with a C]X/H
ꢀ
ꢀ
bond increases to 134 , whereas the thiocarbonyl decreases to
ꢀ
angle of less than 90 for all torsional angles gives another
1
07 . Due to the positioning of the H-bond density donor over
ꢀ
interesting result. For carbonyls the predominant contact is at
ꢀ
the sulfur atom, at C]S/H angles in the region of 90 , it is
likely that the p-electrons of the thiocarbonyl bond are more
low (around 0 or 180 ) torsional angle, indicative of lone pair
bonding. It should be noted that a small proportion of the
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ꢀ
Fig. 11 Contour plots created from entries in the CSD for the density of H-bond donors within the torsional angle range of 60–120 from the acceptor
fragment: (a) NM–C]O carbonyl bond and (b) NM–C]S thiocarbonyl bond.
Table 3 Hydrogen bond metrics for the general carbonyl (NM–C]O) and thiocarbonyl cases (NM–C]S) from entries in the CSD. Average bond
ꢀ
distances and angles are given for each using the full data range (Full) and limiting data to those at a torsional range of 60–120 to the NM–C]X
ꢀ
fragment (Tor 60–120 )
NM–C]O
NM–C]S
ꢀ
ꢀ
Full
1.90
117
0
2.55
125
0
Tor 60–120
Full
2.63
115
0
3.63
114
0
Tor 60–120
ꢁ
O/H/A
C]O/H/
2.06
134
108
2.92
134
92
S–H
2.59
107
97
3.36
85
ꢀ
C]S–H
N–C]S–H
S–Q
C]S–Q
N–C]S–Q
ꢀ
N–C]O/H/
ꢁ
O/Q/A
C]O/Q/
ꢀ
ꢀ
N–C]O/Q/
107
ꢀ
Fig. 12 Contour plots created from entries in the CSD for the density of H-bond donors which are less than 90 to the C]X bond for (a) N–C]O
carbonyl bond and (b) N–C]S thiocarbonyl bond.
ꢀ
hydrogen bond donors are involved in p-type bonding.
However, for thiocarbonyls the majority of H-bond donors that
torsional angle range of 60 to 120 , indicative of p-type bonding.
A minor fraction of the donors bond through the lone pairs as
exhibited by the small contour in the N–C]S plane, Fig. 12.
ꢀ
possess a hydrogen at less than 90 to the C]S bond are in the
3
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matrix least-squares on F for all the data using SHELX soft-
2
Conclusions
29
30,31
ware with the aid of X-Seed.
In conclusion we give evidence that the p-electron density from
thiocarbonyls is an effective H-bond acceptor, particularly in
cases where there is a paucity of other, conventional hydrogen
bond acceptors. Interactions to the p-electron density of thio-
carbonyls are markedly more prevalent than the oxygen
analogues. While the present examples 1–3 exhibit a slightly
weaker than average interaction, the parameters of torsional
angle and donor to acceptor angle show typical directional
behaviour towards the p-electrons.
1
-(2-Amino-phenylene)-3-methyl-thiourea (1). C
8
H
11
N
3
S, M ¼
81.26, colourless block, 0.74 ꢂ 0.33 ꢂ 0.23 mm , monoclinic,
space group P2
3
1
1
ꢁ
/n (no. 14), a ¼ 14.7266(6), b ¼ 7.6637(3),
ꢀ
ꢁ
3
c ¼ 16.2667(7) A, b ¼ 105.323(4) , V ¼ 1770.61(12) A , Z ¼ 8,
ꢁ3
D
c
¼ 1.360 g cm , F000 ¼ 768, Gemini, MoKa radiation, l ¼
ꢁ
ꢀ
0
.71073 A, T ¼ 120(2) K, 2qmax ¼ 58.06 , 8107 reflections
collected, 4136 unique (Rint ¼ 0.0635). Final GooF ¼ 1.064,
R1 ¼ 0.0531, wR2 ¼ 0.1373, R indices based on 3508 reflections
2
with I > 2s(I) (refinement on F ), 235 parameters, 0 restraints. L
p
ꢁ
1
Experimental
and absorption corrections applied, m ¼ 0.312 mm .
Synthesis
1
17 3
-(2-Amino-phenylene)-3-tert-butyl-thiourea (2). C11H N S,
3
M ¼ 223.34, colourless block, 0.39 ꢂ 0.19 ꢂ 0.18 mm , mono-
Compounds 3–6 were prepared by previously published proce-
21
dures.
clinic, space group P2 /n (no. 14), a ¼ 10.6285(4), b ¼ 9.7517(4),
1
ꢁ
ꢀ
ꢁ
3
c ¼ 12.8232(5) A, b ¼ 109.7120(10) , V ¼ 1251.19(9) A , Z ¼ 4,
ꢁ3
D
c
¼ 1.186 g cm , F000 ¼ 480, SMART 1000, MoKa radiation,
ꢁ
Preparation of 1-(2-amino-phenylene)-3-methyl-thiourea (1).
ꢀ
l ¼ 0.71073 A, T ¼ 120(2) K, 2qmax ¼ 60.8 , 11 735 reflections
collected, 3477 unique (Rint ¼ 0.0598). Final GooF ¼ 1.042,
1
,2-Phenylenediamine (0.22 g, 2.05 mmol) and methyl-
isothiocyanate (0.32 g, 4.4 mmol) were ground in a 5 mL
chamber with a ball bearing at 30 Hz for 1 hour. Recrystallisa-
tion from methanol produced crystals which were isolated by
filtration and washed with diethyl ether. Yield ¼ 0.067 g, 0.4
R1 ¼ 0.0373, wR2 ¼ 0.0922, R indices based on 2825 reflections
2
with I > 2s(I) (refinement on F ), 144 parameters, 0 restraints. L
p
ꢁ1
and absorption corrections applied, m ¼ 0.233 mm .
ꢁ
1
mmol, 20%. IR (v, cm ) 3376 (w, N–H), 3299 (m, N–H), 3194 (s,
+
1
1-Methyl-3-[2-(3-methyl-thioureido)-ethyl]-thiourea (3). C H
6
N–H) 1620 (m, Ph–NH
NMR (500 MHz, DMSO-d
H), 6.96 (1H, t, J 7.6, Ar–H), 6.92 (1H, d, J 7.7, Ar–H), 6.72 (1H,
d, J 7.3, Ar–H), 6.54 (1H, t, J 7.6), 4.79 (2H, s, NH ), 2.85 (3H, d,
J 4.1, CH ). { H}– C NMR (126 MHz, DMSO-d ) 182.24,
2
). EI-MS: 182.1 (100%, [M + H] ). H
14
3
N
4
S
2
, M ¼ 206.33, colourless block, 0.09 ꢂ 0.08 ꢂ 0.05 mm ,
6
) 8.83 (1H, s, N–H), 7.13 (1H, s, N–
tetragonal, space group P4
ꢁ
2
/n (no. 86), a ¼ b ¼ 9.5098(5),
ꢁ
3
ꢁ3
c ¼ 10.8333(7) A, V ¼ 979.72(10) A , Z ¼ 4, D
c
¼ 1.399 g cm ,
2
1
13
F
¼ 440, SMART 6000, MoKa radiation, l ¼ 0.71073 Aꢁ ,
000
3
6
ꢀ
T ¼ 200(2) K, 2qmax ¼ 52.7 , 6601 reflections collected, 1002
unique (Rint ¼ 0.0608). Final GooF ¼ 0.921, R1 ¼ 0.0296,
1
44.95, 128.76, 128.08, 123.56, 117.17, 116.46, 32.27. Anal. Calcd
for C H N S: C 53.01, H 6.12, N 23.18%; found: C 52.78, H
8
11
3
wR2 ¼ 0.0625, R indices based on 716 reflections with I > 2s(I)
6
.10, N 23.14%.
2
refinement on F ), 56 parameters, 0 restraints. L and absorp-
(
p
ꢁ1
tion corrections applied, m ¼ 0.498 mm .
Preparation of 1-(2-amino-phenylene)-3-tert-butyl-thiourea (2).
,2-Phenylenediamine (0.6 g, 5.5 mmol) and tert-butyl iso-
1
1
-Methyl-3-[2-(3-methyl-thioureido)-phenyl]-thiourea
(4).
thiocyanate (1.3 g, 11.3 mmol) were dissolved in 30 mL of
methanol and the mixture refluxed for 2 hours. The solvent was
removed in vacuo and the white precipitate washed with hexane.
The product could be isolated by recrystallising the crude
10 14 4 2
C H N S
, M ¼ 254.37, colourless block, 0.28 ꢂ 0.24 ꢂ 0.10
3
mm , monoclinic, space group C2/c (no. 15), a ¼ 18.0632(8), b ¼
ꢁ
ꢀ
7
.5649(3), c ¼ 19.4089(8) A, b ¼ 116.0840(10) , V ¼ 2382.03(17)
3
ꢁ
3
1
Aꢁ , Z ¼ 8, D ¼ 1.419 g cm , F ¼ 1072, SMART 1000, MoKa
product in toluene. Yield ¼ 0.6 g, 2.7 mmol, 49%. H NMR
c
000
ꢁ
ꢀ
radiation, l ¼ 0.71073 A, T ¼ 120(2) K, 2qmax ¼ 60.7 , 13 725
(
CDCl , 400 MHz, J/Hz): 1.43 (9H, s, C-(CH ) ), 4.00 (2H, br,
3 3 3
3
int
reflections collected, 3395 unique (R ¼ 0.0269). Final GooF ¼
NH ), 5.78 (1H, br, NH), 6.71 (1H, dd, J ¼ 8.0, CHAr), 6.77
2
3
3
1.054, R1 ¼ 0.0296, wR2 ¼ 0.0735, R indices based on 2966
(
(
(
1H, d, J ¼ 8.0, CH ), 7.00 (1H, d, J ¼ 8.0, CHAr), 7.10
Ar
2
reflections with I > 2s(I) (refinement on F ), 201 parameters,
3
1
1
3
1H, dd, J ¼ 8.0, CHAr), 7.66 (1H, br, NH). { H}– C NMR
CDCl , 400 MHz): 28.66, 53.68, 116.46, 118.82, 121.10, 128.19,
29.32, 143.25, 179.46. ESI-MS: 224.1 (100%, [M + H] ). Anal.
Calcd for C11 S: C 59.19, H 7.67, N 18.81%; found:
0
restraints. L and absorption corrections applied, m ¼ 0.425
p
3
ꢁ1
+
mm .
1
17 3
H N
1
-Isopropyl-3-[2-(3-isopropyl-thioureido)-phenyl]-thiourea (5).
C 59.12, H 7.72, N 18.81%.
C
14
H
22
N
4
S
2
, M ¼ 310.48, colourless block, 0.28 ꢂ 0.21 ꢂ 0.12
3
ꢂ
mm , triclinic, space group P1 (no. 2), a ¼ 9.4599(6), b ¼
X-Ray diffraction
ꢁ
9
.5946(6), c ¼ 11.0971(7) A, a ¼ 78.9840(10), b ¼ 66.4850(10),
ꢀ
ꢁ
3
ꢁ3
Diffraction quality single crystals were obtained by slow evap-
g ¼ 65.0450(10) , V ¼ 837.03(9) A , Z ¼ 2, D
c
¼ 1.232 g cm ,
ꢁ
oration of ethanol solutions, with the exception of 4, which were
F
000 ¼ 332, SMART 1000, MoKa radiation, l ¼ 0.71073 A, T ¼
ꢀ
obtained from MeOH/H O solution. The diffraction experi-
2
120(2) K, 2qmax ¼ 60.1 , 8785 reflections collected, 4507 unique
(Rint ¼ 0.0439). Final GooF ¼ 1.018, R1 ¼ 0.0392, wR2 ¼
ments were carried out on Gemini, SMART 1000, 6000 or
KappaCCD diffractometer. The crystals were cooled using
0.0918, R indices based on 3673 reflections with I > 2s(I)
2
(refinement on F ), 181 parameters, 0 restraints. L
Cryostream (Oxford Cryosystems) open-flow N
2
cryostats. The
p
and
ꢁ1
structures were solved by direct methods and refined by full-
absorption corrections applied, m ¼ 0.315 mm .
CrystEngComm, 2011, 13, 3202–3212 | 3211
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View Article Online
1
-Methyl-3-[6-(3-methyl-thioureido)-pyridin-2-yl]-thiourea (6).
6 I. Dance and M. Scudder, J. Chem. Soc., Chem. Commun., 1995, 1039.
7
F. H. Allen, J. A. K. Howard, V. J. Hoy, G. R. Desiraju, D. S. Reddy
and C. C. Wilson, J. Am. Chem. Soc., 1996, 118, 4081.
J. L. Atwood, F. Hamada, K. D. Robinson, G. W. Orr and
R. L. Vincent, Nature, 1991, 349, 683.
C H N S , M ¼ 255.36, colourless block, 0.24 ꢂ 0.10 ꢂ 0.01
9
13
3
5 2
ꢂ
mm , triclinic, space group P1 (no. 2), a ¼ 5.798(2), b ¼ 9.447(4),
8
ꢁ
ꢀ
c ¼ 11.167(4) A, a ¼ 87.646(7), b ¼ 75.043(6), g ¼ 75.422(6) ,
ꢁ
3
ꢁ3
9 C. S. Page and H. S. Rzepa, Electronic Conference Trends Org. Chem.,
1995, www.ch.ic.ac.uk/etoc/papers/47/.
V ¼ 571.7(4) A , Z ¼ 2, D
c
¼ 1.483 g cm , F000 ¼ 268, SMART
ꢁ
6
5
000, MoKa radiation, l ¼ 0.71073 A, T ¼ 120(2) K, 2qmax
¼
1
0 C. A. Ilioudis, M. J. Bearpark and J. W. Steed, New J. Chem., 2005,
ꢀ
5.0 , 4141 unique reflections (see CIF† for discussion of twin-
2
11 N. Sklar, M. E. Senko and B. Post, Acta Crystallogr., 1961, 14, 716.
9, 64.
ning). Final GooF ¼ 1.070, R1 ¼ 0.0450, wR2 ¼ 0.1149, R
1
1
2 P. Vaughan and J. Donohue, Acta Crystallogr., 1952, 5, 530.
3 S. Swaminathan, B. M. Craven and R. K. McMullan, Acta
Crystallogr., Sect. B: Struct. Sci., 1984, 40, 300.
indices based on 3349 reflections with I > 2s(I) (refinement on
2
F ), 148 parameters, 0 restraints. L
p
and absorption corrections
ꢁ1
applied, m ¼ 0.446 mm .
1
1
4 S. Swaminathan, B. M. Craven, M. A. Spackman and R. F. Stewart,
Acta Crystallogr., Sect. B: Struct. Sci., 1984, 40, 398.
5 M. M. Elcombe and J. C. Taylor, Acta Crystallogr., Sect. A: Cryst.
Phys., Diffr., Theor. Gen. Crystallogr., 1968, 24, 410.
CSD search
32–34
16 I. Takahashi, A. Onodera and Y. Shiozaki, Acta Crystallogr., Sect. B:
Struct. Sci., 1990, 46, 661.
CSD search and Isogen plot method. A search of the CSD
was undertaken using the central fragment of NM–C]X (NM ¼
any non-metal atom, X ¼ S, O) and a contact group of H–Q (Q ¼
N,O) where an X/H contact (distance between atoms no larger
than sum of van der Waals radii) existed. Similar searches were
conducted applying one of the following two constraints: NM–
1
7 A. Masunov and J. J. Dannenberg, J. Phys. Chem. B, 2000, 104, 806.
18 F. H. Allen, C. M. Bird, R. S. Rowland and P. R. Raithby, Acta
Crystallogr., Sect. B: Struct. Sci., 1997, 53, 680.
1
9 S. B. Novakovi ꢀc , B. Fraisse, G. A. Bogdanovi ꢀc and A. Spasojevi ꢀc -
deBir ꢀe , Cryst. Growth Des., 2007, 7, 191.
2
0 S. J. Brooks, P. R. Edwards, P. A. Gale and M. E. Light, New J.
Chem., 2006, 30, 65.
21 M. L. Soriano, J. T. Lenthall, K. M. Anderson, S. Smith and
ꢀ
ꢀ
C]X/H torsional angles limited to between 60 and 120 , or
ꢀ
C]X/H angle no greater than 90 . The parameters and coor-
J. W. Steed, Chem.–Eur. J., 2010, 16, 10818.
dinate files were saved for these searches and used to generate
scatter plots in the Isogen program. Contour scatter plots of the
donor atom, Q, were generated in Rasmol with an internal
scaling of 20 (red), 40 (green), and 80 (blue). The maximum
density was found by setting all scales to 99, and measurements
were taken using the tools provided by the program.
2
2
2 J. F. Fernandez-Bertran, Pure Appl. Chem., 1999, 71, 581.
3 A. L. Garay, A. Pichon and S. L. James, Chem. Soc. Rev., 2007, 36,
846.
2
2
4 A. N. Swinburne and J. W. Steed, CrystEngComm, 2009, 11, 433.
5 J. J. McKinnon, M. A. Spackman and A. S. Mitchell, Acta
Crystallogr., Sect. B: Struct. Sci., 2004, 60, 627.
26 P. A. Wood, J. J. McKinnon, S. Parsons, E. Pidcock and
M. A. Spackman, CrystEngComm, 2008, 10, 368.
2
2
2
7 K. M. Anderson, A. E. Goeta and J. W. Steed, Cryst. Growth Des.,
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8 I. J. Bruno, J. C. Cole, J. P. M. Lommerse, R. S. Rowland, R. Taylor
and M. L. Verdonk, J. Comput.-Aided Mol. Des., 1997, 11, 525.
9 G. M. Sheldrick, Acta Crystallogr., Sect. A: Found. Crystallogr., 2008,
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212 | CrystEngComm, 2011, 13, 3202–3212
This journal is ª The Royal Society of Chemistry 2011