Evaluation of intermolecular interactions in thioxanthone derivatives: Substituent effect on crystal diversity

Article abstract of DOI:10.1039/c0ce00783h

A family of 9H-thioxanthen-9-one derivatives and two precursors, 2-[(4-bromophenyl)sulfanyl]-5-nitrobenzoic acid and 2-[(4-aminophenyl)sulfanyl]- 5-nitrobenzoic acid, were synthesized and studied in order to assess the role of the different substituent gr

Full text of DOI:10.1039/c0ce00783h

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PAPER
Evaluation of intermolecular interactions in thioxanthone derivatives:
substituent effect on crystal diversity†
a
ab
a
C. Jacob, Fatima M. da Piedade, M. Paula Robaloac and M. Teresa Duarte
*
ꢀ
Received 27th October 2010, Accepted 5th January 2011
DOI: 10.1039/c0ce00783h
A family of 9H-thioxanthen-9-one derivatives and two precursors, 2-[(4-bromophenyl)sulfanyl]-5-
nitrobenzoic acid and 2-[(4-aminophenyl)sulfanyl]-5-nitrobenzoic acid, were synthesized and studied in
order to assess the role of the different substituent groups in determining the supramolecular motifs.
From our results we can conclude that Etter’s rules are obeyed: whenever present the –COOH head to
head strong hydrogen bonding dimer, R2 (8) synthon, prevails as the dominant interaction. As for
2
–NH2, the best donor when present also follows the expected hierarchy, an NH/O(COOH) was
formed in the acid precursor (2) and an NH/O(C]O) in the thioxanthone (4). The main role played
by weaker hydrogen bonds such as CH/O, and other intermolecular interactions, p–p and Br/O, as
well as the geometric restraints of packing patterns shows the energetic interplay governing crystal
packing. A common feature is the relation between the p–p stacking and the unit cell dimensions. A
new synthon notation, R0, introduced in this paper, refers to the possibility of accounting for intra- and
intermolecular interactions into recognizable and recurring aggregate patterns.
effective approach for structural design and prediction. Identi-
Introduction
fication of the synthons between various functional groups can
undoubtedly simplify the description of crystal structures and, of
further importance, provide new insights into the inherent role of
molecular recognition and assembly.12
Crystal design and engineering has received much attention in
recent years as its implications extend to material science, solid-
state reactions and synthesis, and drug development, just to refer
to some applications.1–5
Moreover, the introduction of functional groups in the main
skeleton of a molecule can endow structural variability and
influence the structural assemblies, since they may display
different hydrogen-bonding capabilities and potential steric/
electronic effects. The interplay becomes even more interesting
when a molecule has more than one functional group that can
attract adjacent molecules by hydrogen bonding, epitomized by
various synthons.11b,13,14
One of the most important issues in this field is the rational
design and structural control of molecular packing, which affect
and control the macroscopic properties of materials (e.g., elec-
trical, optical and electronic properties).4–6 A comprehensive
understanding of supramolecular systems is primarily dependent
on the knowledge of intermolecular interactions controlling the
molecular aggregation, with major emphasis on hydrogen and
halogen bonding as well as aromatic stacking.1,3,6–9,11 In this
context hydrogen bonding generally plays a dominant role but
halogen bonds, p–p, CH/X, Br/O and S/O interactions also
provide weaker but determinant packing motifs, which support
the evaluation of the resulting molecular assemblies.1–4,9–11
A supramolecular synthon, a recurring hydrogen-bonding
pattern, reliable in crystal structure elucidation, represents an
Looking forward new ligands with different architectures,
geometries and environments appropriate for the coordination
to metal centres, leading to organometallic complexes with
potential NLO properties, we synthesized several 9H-thio-
xanthen-9-ones and 9H-thioxanthen-9-thiones with different
substituent groups. We will present here a study for two
precursors, 2-[(4-bromophenyl)sulfanyl]-5-nitrobenzoic acid and
2-[(4-aminophenyl)sulfanyl]-5-nitrobenzoic acid, where the
presence of the carboxylic moiety prevails in determining the
supramolecular architecture, and we will also analyze the pack-
ings observed in different substituted 9H-thioxanthen-9-ones,
where the role of the different substituent groups in determining
the various assemblies obtained has been discussed. Systematic
comparisons were performed with data from similar compounds
retrieved from Cambridge Structural Database (CSD) when
available.15
a
ꢀ
Centro de Quımica Estrutural, Instituto Superior Tecnico, TU Lisbon, Av.
Rovisco Pais, 1049-001 Lisbon, Portugal. E-mail: teresa.duarte@ist.utl.pt;
ꢀ
Fax: +351-218417246; Tel: +351-218419282
b
ꢀ
Departamento de Quımica e Bioquımica, FCUL, Campo Grande, 1749-
ꢀ
016 Lisbon, Portugal
c
Departamento de Engenharia Quımica, Instituto Superior de Engenharia
ꢀ
de Lisboa, Rua Conselheiro Emꢀıdio Navarro, 1, 1959-007 Lisbon, Portugal
† Electronic supplementary information (ESI) available. CCDC
reference numbers 798531–798535. For ESI and crystallographic data
in CIF or other electronic format see DOI: 10.1039/c0ce00783h
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All the 9H-thioxanthen-9-one derivatives and precursors were
characterized by spectral techniques such as FTIR, 1H NMR and
13C NMR and followed by single crystal X-ray diffraction
studies, for the cases where suitable crystals were obtained.
Results and discussion
Synthesis of the 9H-thioxanthen-9-one derivatives
The formation of the substituted 9H-thioxanthen-9-one skeleton
has been carried out by a multi-step synthesis using suitable
methods reported in the literature (Scheme 1). The first step,
leading to the benzoic acid derivatives (1 and 2), followed the
methods described in the literature.16–18 The benzoic acids were
converted to the respective 9H-thioxanthen-9-ones (3 and 4)
through an intramolecular Friedel–Crafts reaction with poly-
phosphoric acid at 110 ꢀC. The functionalization of these 9H-
thioxanthen-9-ones with a nitrile substituent was performed by
a Sandmeyer reaction following the literature methods,19,20
leading to the 2-cyano-7-nitro-9H-thioxanthen-9-one (7). The
formation of the acetylene derivative, 2-ethinyl-7-nitro-9H-thi-
oxanthen-9-one (6), was obtained by Sonogashira coupling
following the literature procedures21–23 and further desilylation of
the obtained compound with ammonium fluoride.
Molecular and supramolecular structures
Benzoic acid derivatives: precursors from the 9H-thioxanthen-9-
one unit. Compounds 1, 2-[(4-bromophenyl)sulfanyl]-5-nitro-
benzoic acid, and 2, 2-[(4-aminophenyl)sulfanyl]-5-nitrobenzoic
ꢁ
acid, crystallized respectively in the triclinic space group P1, with
two molecules in the asymmetric unit, and in the monoclinic
space group C2/m. The molecular structures are displayed in
Fig. 1 and 2, and bond distances and angles are listed in Table
S1†. Most relevant hydrogen bond and intermolecular interac-
tions are presented in Table 1.
The two molecules of compound 1 present similar bond
distances and angles, the only noticeable difference being the
Scheme 1 Reagents and conditions: (i) Na2CO3 anhydrous (1 eq), powder copper (0.02 eq), DMF, reflux; (ii) polyphosphoric acid, 110 ꢀC, 5 h; (iii)
NaNO2, HCl/H2O, ꢁ5 ꢀC; (iv) CuCN, KCN 0.1 M, ꢁ5 ꢀC; (v) Pd(PPh3)2Cl2, PPh3, Me3SiCCH (excess), Et3N (excess), CuI, THF, rt; (vi) NH4F (excess),
THF/methanol (1 : 3), reflux 2 h.
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this case the two aromatic rings connected by the sulfur bridge
are also distorted, presenting a torsion angle C(3)–C(4)–S(1)–
C(7) of 93.0(4)ꢀ.
In Fig. 3 an overlay of the three molecules (1A, 1B and 2)
clearly shows the different conformations adopted. An intra-
molecular OCOOH/S interaction24 is observed in the three
ꢂ
ꢂ
molecules, 2.75(1) A in molecule 1A, 2.74(1) A in 1B and 2.69(1)
ꢂ
A in 2. The correlation between these distances and the torsion
angles suggests different values for molecules 1A and 1B.
However due to the tilt in the carboxylic moiety, the relative
position of the oxygen atom O3 in both molecules remains
practically the same and thus the distances become very similar.
As expected the presence of the carboxylic group induces the
2
formation of the homosynthon R2 (8) in both compounds, and
dimers are obtained (Scheme 2).
Fig. 1 RASTER3D diagram for 2-[(4-bromophenyl)sulfanyl]-5-nitro-
benzoic acid, molecule 1A, with the atomic labeling scheme and ellipsoids
at 50% probability level. The intramolecular S/O interaction is shown.
In compound 1 these dimers are linked together via CH/
2
O1NO bonds,25 forming an R2 (10) synthon, generating a supra-
2
molecular array that can be best described as a linear chain.
These chains are obtained due to the cooperative effect of the
2
2
R2 (8) and R2 (10) synthons, growing in the [101] direction due to
the matching directions of the synthon vectors, with an angle of
1.79ꢀ (see Fig. 4a). Both synthons lie within the same plane,
2
forced by the geometric rigidity of the R2 (10) synthon, as the
hydrogen bond is established between the oxygen atom of the
NO2 group and the H(C) atom in the ortho position to the nitro
group. The self-assembly process produces a 2D grid network
through Br/O2NO interactions,26 3.179 and 3.102 A, using the
ꢂ
2
other nitro oxygen atom (Fig. 4b). The supramolecular pattern is
formed by a sequence of alternated rings, A and B, described as
being R044(30) and R022(26), respectively, synthons constructed
with the interplay of intermolecular Br/O and intramolecular
S/O interactions (see Scheme 3). The new notation R0 refers to
the possibility of also accounting for intra/intermolecular inter-
actions, in the definition of the molecular recognition pattern.
Both intra- and intermolecular interactions, such as the ones
considered here, are recognized to be important driving forces in
supramolecular assembly. We included in the new notation the
possibility of accounting for weak interactions into recognizable
and recurring aggregate patterns.27
Fig. 2 RASTER3D diagram of 2-[(4-aminophenyl)sulfanyl]-5-nitro-
benzoic acid (2) showing the molecular conformation of the molecule, the
atomic labeling scheme and the S/O interaction. Ellipsoids are drawn at
50% probability level.
Table 1 List of hydrogen bonds and intermolecular interactions for
compounds 1 and 2
This layered structure packs through p–p interactions of 3.41
A, the interaction involving the delocalized systems of the NO2
ꢂ
ꢂ
Compound D–H/A
d (H/A)/A d (D/A)/A <(DHA)/deg
ꢂ
group and of the nitrophenyl ring.26a,28
1
2
O4AH4A/O3B 1.85
2.662(5)
2.636(5)
3.356(6)
3.437(6)
3.41
2.649(4)
3.030(3)
3.471(5)
3.351(5)
3.64
176
160
168
174
In compound 2 dimers interact in a different way due to the
replacement of the Br by an amino group, thus promoting strong
hydrogen bond through NH/O4COOH in a direction 41.7ꢀ from
O4BH4B/O3A 1.85
C9BH9B/O1A 2.46
C9AH9A/O1B 2.53
p–pa
O4H4/O3
N1H1/O4
C3H3/O2
C9H9/O1
p–p
1.90
2.73
2.62
2.69
175
103
146
131
a
Distance between centroids of the NO2 group and of the nitrophenyl
ring.
torsion angle C(3)–C(4)–S(1)–C(7), respectively 66.7(5)ꢀ in A and
88.9(5)ꢀ in B. These values show that there is no delocalization
between the two aromatic rings through the sulfur atom.
In compound 2, the Br is substituted by the amino group,
–NH2, but the overall geometry of the molecule is maintained. In
Fig. 3 (a) Overlay of molecules 1A and 1B and compound 2 (green—1A;
blue—1B; element coloured—2). (b) The similarities and differences in
both torsion angles and intramolecular OCOOH/S interaction are
evident.
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composed of two concurrent linear chains making an angle of
ꢂ42ꢀ (Fig. 5b).
The supramolecular 3D framework is further completed by
parallel superimposition of these layers, through p–p interac-
ꢂ
tions, 3.64 A reinforced by a CH/O2NO non-classical hydrogen
2
bond.
The cooperative effect30 of weak hydrogen bonds, CH/O,
intermolecular interactions, p–p, Br/O, and their relative
importance in determining the crystal structure are evidenced in
the supramolecular packings observed (Fig. 6).
Scheme 2 Synthons defining the linear chain observed in 1. Synthon
R2 (10) is responsible for the 2D grid obtained in compound 2.
2
2
the R2 (8) vector, forming an R044(20). The carboxylic oxygen
Substituted 9H-thioxanthen-9-ones: 2-Bromo-7-nitro-9H-thio-
xanthen-9-one (3), 2-amino-7-nitro-9H-thioxanthen-9-one (4) and
2-ethinyl-7-nitro-9H-thioxanthen-9-one (6). Compounds 3, 4 and 6
haveshowntocrystallizerespectivelyinthemonoclinicspacegroup
atom, O4, acts as both donor and acceptor (Fig. 5a). This motif is
ꢂ
further sustained via an S/p interaction of 3.61 A, value within
the range proposed by Reedijk et al.29
ꢁ
P21/n (3 and 4) and in triclinic space group P1, respectively. The
In this compound a 2D grid is obtained through the interac-
tion CH/O1NO , also observed in compound 1, involving the
NO2 group and the aromatic H(C) atom in the ortho position to
2
the nitro group, forming an R2 (10) synthon. Thus the 2D layer is
molecular structures are presented in Fig. 7–9, main bond distances
and angles are listed in Table S2†. Most relevant hydrogen bond
and intermolecular interactions are presented in Table 2.
2
Fig. 4 Compound 1, 2-[(4-bromophenyl)sulfanyl]-5-nitrobenzoic acid: (a) view of the linear chain of dimers obtained through CH/O1NO evidencing
2
the small angle (of 1.79ꢀ) between the vectors and (b) view of the 2D grid constructed using synthons R044(30) (ring A) and R022(26) (ring B).
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Scheme 3 Geometric display of the new synthons, R0, observed in the supramolecular arrangement of compounds 1 and 2.
2-Bromo-7-nitro-9H-thioxanthen-9-one (3). With the ring
closure, we obtain a perfectly planar molecule and the most
2
important molecular synthon, R2 (8), due to the COOH moiety
These herringbone chains interact with each other through
CH/O1NO and CH/OC]O hydrogen bonds and pack,
2
through p–p interactions, in a staggered head to tail overlap,
within the centrosymetrically related chain with an interlayer
distance of ꢂ3.42 (Fig. 11b). This packing is further assisted by
disappears, changing the supramolecular arrangement of the
resulting product.
In compound 3 an extended ribbon is obtained via CH/ONO
an NH/ONO .
2
2
interactions using both O atoms of the nitro group (CH2/
3
O1NO , CH8/O2NO ) (Fig. 10a) forming an R3 (17) synthon.
2-Ethinyl-7-nitro-9H-thioxanthen-9-one (6). Making R ¼
CCH in compound 6, the overall geometry of the molecule is
again unchanged, the supramolecular motif now being a linear
chain along a, built by CH/O3C]O (CH8/O3C]O) hydrogen
bonds again using H8, the hydrogen atom in the meta position to
the NO2 group, as the best donor (Fig. 12a).
2
2
These ribbons, running in opposite directions, interact through
CH/OC]O and CH/Br weak hydrogen bonds expanding into
a 2D layer (Fig. 10b).25c,26b
ꢂ
These layers pack through p–p interactions, 3.67 A, the
overlap is staggered in a head to tail mode (Fig. 10c) and the
packing is further supported by CH8/O3C]O interactions. The
carbonyl O atom acts as a bifurcated acceptor while the aromatic
hydrogen atom H8, in the meta position to the NO2 group, acts
as a bifurcated donor (Fig. S1†). This shows that the hierarchy is
followed and that both the best donor and acceptor in the
molecule are engaged in the intermolecular interaction support-
ing the 3D crystal packing.27
A 2D grid is enforced by the CH/O2NO hydrogen bond
2
array, based on CH15/O2NO , using the second best donor,
2
the hydrogen atom H15 of the ethinyl group, and also CH2/
O2NO hydrogen bond (Fig. 12b). This layer, due to the
2
relative positioning of the functional groups, is the product of
an energetic balance between the most favorable intermolec-
ular interactions and the geometric stability of the packing
pattern.31
2-Amino-7-nitro-9H-thioxanthen-9-one (4). When Br was
substituted by NH2 the overall molecular geometry again does
not change, the best-donor–best-acceptor rule prevails,27 and the
supramolecular array obtained is a herringbone chain along [101]
based on NH/O3C]O hydrogen bonds (Fig. 11a).
These layers pack as expected through p–p interactions
further supported by weak CCH/ONO interactions, promoting
the formation of a distorted quasi honeycomb array, where the
molecules overlay in a staggered mode, slipped along the longer
axis (Fig. 12c and d).
2
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2
Fig. 5 Compound 2, 2-[(4-aminophenyl)sulfanyl]-5-nitrobenzoic acid: (a) view of the chain propagating along [001] obtained through R2 (8) and
R044(20) and (b) 2D grid showing the two concurrent linear chains making an angle of ꢂ42ꢀ.
Substituent effect and crystal diversity
nature of the two different substituents. In the case of Br, the
Br/ONO and CH/ONO interactions determine a 2D grid
2
2
We have characterized the supramolecular motifs and concluded
about those governing the crystal packing in the above studied
compounds. In the two nitrobenzoic acid precursors, dimers are
formed by sequential R044(30) (ring A) and R022(26) (ring B)
synthons (Scheme 3). In compound 2, the presence of –NH2,
a strong donor, determines both the primary and secondary
formed due to the prevalent carboxylic–carboxylic R2 (8)
2
2
patterns, where the 2D grid is constructed using the R2 (8) and
R044(20) synthons. The –NO2 group seems to play a more
homosynthon.1,4 The secondary motif strongly depends on the
ꢂ
ꢂ
Fig. 6 Similar packing of layers in both compounds 1 (a) and 2 (b), making use of p–p interactions (ꢂ3.41 A and ꢂ3.64 A). The p–p stacking is
obtained using different delocalized systems; in compound 1 the interactions are between the NO2 and the nitrophenyl ring while in 2 are between the
centroids of two nitrophenyl rings.
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–C^CH) occupy position 2. These differences are expected to
affect the hydrogen bonding supramolecular recognition pattern
and further the crystal packing.
Trying to extend the analysis to similar thioxanthen-9-one
derivatives, a search in CSD15 was performed and none were
found with substituents in positions 2 and 7. However some
derivatives with different functional groups in different positions
were also analyzed and compared.
Etter’s rules27 state that hydrogen bonds are shaped in a hier-
archical fashion (best-donor to best-acceptor and second best-
donor to second best-acceptor, etc.) and in accordance to this
when NH2 is present (compound 4) an NH/OC]O hydrogen
bond governs the formation of a 1D herringbone chain never
extended to a layered structure like what happens in compounds
3 and 6.
Fig. 7 RASTER3D diagram of 2-bromo-7-nitro-9H-thioxanthen-9-
one, 3, showing the atomic labeling scheme, ellipsoids are drawn at 50%
probability level.
In compound 3 non-classical CH/ONO hydrogen bonds
2
determine the observed 1D ribbon which is further extended to
a 2D sheet by means of weak CH/OC]O and CH/Br inter-
actions. It can also be said that the hierarchy of Etter’s rules27
also applies, even though both best donor (CH8) and best
acceptor (O3C]O) are engaged in bifurcated interactions; the
–NO2 behaves as the second best acceptor competing with Br. In
6 a linear chain is obtained through CH8/O3C]O, best donor–
best acceptor groups present and a layer is obtained using the
expected hierarchy for CCH/O2NO hydrogen bonds. Weak
2
CH/O hydrogen bonds are thus determinant in the supramo-
lecular arrangement.
In all these three compounds the energetic stability of the
geometric packing patterns competes with the weak intermolec-
ular interactions (CH/X, X]O, Br and p–p), this interplay
being responsible for the overall crystal packing.
Fig. 8 RASTER3D diagram of 2-amino-7-nitro-9H-thioxanthen-9-one
(4) displaying the atomic labeling scheme with ellipsoids drawn at 50%
probability level.
Also inherent to these structures is the p–p stacking,
a common pattern reflected in the similarity of the unit cell
dimensions,31 7.772(3), 7.665(3) and 7.256(2) A for compounds 3,
ꢂ
4 and 6 respectively (see Table 3).
In the data retrieved from CSD,15 all referred by their CCDC
ref codes, three compounds had a Cl atom as a functional
group, CLTXAN with a Cl in position 8; UDASEY and
FAYDIT with a Cl atom in position 1 and an octyloxy and
a propoxy group in position 4, respectively. Interactions of the
type CH/Cl were not found in the supramolecular assembly
due to both the relative positioning of the Cl atoms and the
bulkiness of substituents in position 4. However in all of them
the CH/OC]O hydrogen bond was found to dictate the
packing arrangement.
Fig. 9 RASTER3D diagram of 2-ethinyl-7-nitro-9H-thioxanthen-9-one
(6), with atomic labeling scheme and ellipsoids drawn at 50% probability
level.
A 2,4-diethyl derivative HOLPAA was found to display CH/
OC]O intermolecular interaction, which was also present in
LEGSAR, LEGSEV and LEGSIZ, a 2, 3 and 4 methyl deriva-
tives. We can conclude that for these compounds Etter’s rule is
obeyed as the best acceptor, the O atom of the carbonyl group,
always interacts with the best H donor, either a C from the
phenyl ring or from the methyl substituent.
important role in compound 1 where it competes with Br than in
compound 2. Nevertheless in both cases a layered structure is
obtained.
The new notation R0 introduced in this paper refers to the
possibility of accounting for intra- and intermolecular interac-
tions in the definition of the molecular recognition pattern and
was used in the description (Scheme 3).
Conclusions
In compounds 3, 4 and 6 the influence of substituent groups in
the main backbone of a thioxanthone’s family can be studied.
Besides the inherent S and carbonyl O atoms, a NO2 group
resides in position 7 and different substituents (–Br, –NH2 and
From our results we can conclude that whenever present, the
–COOH head to head strong hydrogen bonding dimer, in the
2
typical R2 (8) motif, prevails as the dominant interaction for
the crystal packing. As for –NH2, the best donor when present
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Table 2 List of hydrogen bonds and intermolecular interactions for compounds 3, 4 and 6
ꢂ
ꢂ
Compound
D–H/A
d (H/A)/A
d (D/A)/A
<(DHA)/deg
3
C2H2/O1
C8H8/O2
C8H8/O3
C6H6/O3
C11H11/Br1
p–pa
2.58
2.56
2.61
2.62
3.04
3.303(8)
3.362(11)
3.260(11)
3.381(11)
3.909(9)
3.67
135
144
127
140
155
4
N1H1B/O3
N1H1A/O1
N1H1A/O2
C8H8/O1
C3H3/O3
p–pa
2.11
2.68
2.70
2.45
2.70
2.955(3)
3.332(3)
3.503(3)
3.247(4)
3.478(4)
3.71
171
135
158
144
142
6
C8H8/O3
C15H15/O2
C15H15/O1
C2H2/O2
p–pa
2.50
2.65
2.71
2.67
3.256(6)
3.382(5)
3.421(5)
3.548(6)
3.64
139
136
133
159
a
Distance between centroids of the phenyl rings.
also follows the expected hierarchy, an NH/OCOOH was formed
in the acid precursor (2) and an NH/OC]O in the thioxanthones
(4). The main role played by weaker hydrogen bonds like CH/
O, and intermolecular interactions, p–p, Br/O and their
importance in determining the crystal structure are also evi-
denced. A common feature is the relation between the p–p
packing and the unit cell dimensions.
tunable crystals is still a challenge. Presently we are introducing
different functional groups in order to obtain overcrowded
molecules displaying helical environments for direct coordina-
tion to metal centres leading to frameworks with nonlinear
optical properties.
The subtleties of crystal packing are illustrated by the varia-
tions in the structures due to the energetic interplay of strong and
weak hydrogen bonds, halogen bonds, intermolecular interac-
tions and geometry of packing patterns. Structure prediction
based on crystal engineering principles in order to produce
Experimental section
Preparative methods
Solvents and reagents were reagent-grade and commercially
available and used without further purification unless otherwise
3
Fig. 10 Packing of 2-bromo-7-nitro-9H-thioxanthen-9-one, compound 3: (a) ribbons obtained via R3 (17) synthons, (b) layers formed by ribbons
running in opposite directions, connected by CH6/OC]O and CH11/Br interactions, (c) detail of the p–p stacking mode.
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Fig. 11 (a) Herringbone chain obtained via NH/O3C]O, (b) detailed view showing the interactions between the herringbone chains, here presented in
different colors, a color code is also used for the different NH/O and CH/O intermolecular bonds (green—NH1B/O1; blue—NH1A/O3; brown—
CH8/O1; pink—CH3/O3) (c) view along a showing p–p interactions within the herringbone chains further assisted by an NH/ONO and a detail of
the staggered head to tail overlap.
2
stated. Compounds 2-[(4-bromophenyl)sulfanyl]-5-nitrobenzoic
acid (1) and 2-bromo-7-nitro-9H-thioxanthen-9-one (3) were
prepared according to literature procedures.18 IR spectra were
recorded in KBr pellets on Jasco spectrophotometers model
FT/IR-430 and FT/IR-4100, with acquisition and data
management software (spectra manager, version 2.0), only the
Recrystallization of 1, by cooling a heated supersaturated
methanol solution, gave yellow crystals suitable for X-ray
diffraction.
Yield: 83%. IR (KBr): n(OH) 3425, n(CO) 1694, n(NO2) 1509,
1345 cmꢁ1. 1H NMR (CDCl3): 6.86 (d, 1H, JHH ¼ 9, H5), 7.45 (d,
2H, JHH ¼ 8.5, H4, H9a), 7.64 (d, 2H, JHH ¼ 8.5, H3, H1), 8.05
(dd, 1H, JHH ¼ 2.6, JHH ¼ 9, H6), 8.08 (br, OH), 8.95 (d, 1H,
JHH ¼ 2.5, H8). 13C NMR (CDCl3): 125.07 (C2), 126.21 (C8),
126.90 (C6), 126.98 (C5), 129.87 (C4a), 133.58 (C3, C1), 137.46
(C8a, C4, C9a), 144.35 (C10a), 152.48 (C7), 163.09 (C9).
Recrystallization of 3 from a saturated dichloromethane
solution, double layered with n-hexane and stored at room
significant bands are cited. H and 13C NMR were recorded in
1
[d1]-chloroform solutions on a Varian Unity 300, (1H, 299.95
MHz), a Bruker Advance III 300 (1H, 300 MHz, 13C, 75.47 MHz)
and Bruker Advance 400 (1H, 400 MHz, 13C, 100.62 MHz)
spectrometers at probe temperature, using Me4Si as an internal
reference. Coupling constants are indicated in Hz.
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3
Fig. 12 Packing of compound 2-ethinyl-7-nitro-9H-thioxanthen-9-one (6): (a) 1D chain built by CH/O3C]O; (b) 2D grid obtained via R3 (18) and
2
R3 (17) synthons; (c) views showing the detailed p–p packing among the layers and the formation of the distorted quasi honeycomb array due to the
bifurcated CCH/ONO interactions; (d) detail of the p–p stacking showing the staggered overlay of the molecules, slipped along the longer axis.
2
temperature, gave yellow crystals suitable for single crystal X-ray
diffraction studies.
Yield: 61%. IR (KBr): n(CO) 1642, n(NO2) 1509, 1340 cmꢁ1. 1H
2-(2-Trimethylsilyl)ethinyl-7-nitro-9H-thioxanthen-9-one (5)
This compound was prepared from 2-bromo-7-nitro-9H-thio-
xanthen-9-one (3) following a procedure described earlier.23 To
a mixture of 3 (500 mg, 1.487 mmol), [Pd(PPh3)2Cl2] (52 mg,
0.074 mmol), PPh3 (11 mg, 0.037 mmol) and 8 mL of triethyl-
amine in dry THF (30 mL), a solution of trimethylsilylacetylene
(450 mL, 4.459 mmol) in 2 mL of dry THF was added over 30
min. The mixture was stirred for 1 h at room temperature and
CuI (3.4 mg, 0.018 mmol) was then added. After being stirred for
NMR (CDCl3): 7.53 (d, 1H, JHH ¼ 8.6, H4), 7.77 (d, 1H, JHH
¼
8.8, H5), 7.83 (dd, 1H, JHH ¼ 2.2, JHH ¼ 8.6, H3), 8.46 (dd, 1H,
JHH ¼ 2.5, JHH ¼ 8.8, H6), 8.78 (d, 1H, JHH ¼ 2.1, H1), 9.45 (d,
1H, JHH ¼ 2.4, H8). 13C NMR (CDCl3): 121.71 (C2), 125.70 (C8),
126.25 (C6), 127.58 (C3), 127.78 (C5), 129.18 (C9a), 129.83
(C4a), 131.68 (C8a), 132.84 (C1), 136.35 (C4), 138.41 (C10a),
151.23 (C7), 179.39 (C9).
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5 days, the solvent was evaporated, and the residue was treated
with dichloromethane. Filtration through silica gel, the evapo-
ration of the solvent and washing with diethyl ether yielded 0.41
g of pure 5. Yield: 77%. IR (KBr): n(CC) 2152, n(CO) 1641,
for 5 h at this temperature. The dark mixture was allowed to cool
to 70 ꢀC and ice was added. After stirring overnight, the mixture
was filtered and the precipitate washed with 5% NaOH (200 mL)
and water affording an orange solid. Further recrystallization
from a saturated DMSO solution, double layered with ethyl
acetate and stored at room temperature, gave orange single
crystals suitable for single crystal X-ray diffraction studies.
Yield: 62%. IR (KBr): n(NH2) 3462, 3363, n(CO) 1629, n(NO2)
n(NO2) 1519, 1340 cmꢁ1 1H NMR (CDCl3): 0.29 (s, 9H,
.
(CH3)3Si), 7.54 (d, 1H, JHH ¼ 8.3, H3), 7.74 (m, 2H, H4, H5), 8.41
(d, 1H, JHH ¼ 2.5, JHH ¼ 8.9, H6), 8.66 (d, 1H, JHH ¼ 1.6, H1),
9.39 (d, 1H, JHH ¼ 2.3, H8). 13C NMR (CDCl3): ꢁ0.14
(Si(CH3)3), 97.30 (C12), 102.96 (C11), 122.89 (C2), 125.56 (C8),
126.06 (C6), 126.21 (C3), 127.49 (C5), 128.33 (C9a), 129.25
(C4a), 133.51 (C1), 135.61 (C8a), 135.81 (C4), 143.67 (C10a),
146.22 (C7), 177.79 (C9).
1509, 1335 cmꢁ1. H NMR [(CD3)2CO]: 5.39 (sl, 2H, NH2) 7.25
1
(d, 1H, JHH ¼ 9, H3), 7.55 (d, 1H, JHH ¼ 9, H4), 7.82 (s, 1H, H1),
7.99 (d, 1H, JHH ¼ 8.7, H5), 8.45 (d, 1H, JHH ¼ 8.7, H6), 9.44 (s,
1H, H8). 13C NMR [(CD3)2CO]: 114.71 (C1), 124.81 (C9a),
125.57 (C3), 128.14 (C8), 129.18 (C6), 131.48 (C4), 131.55 (C4a),
132.32 (C5), 132.68 (C8a), 148.35 (C2), 148.96 (C10a), 153.01
(C7), 181.68 (C9).
2-Ethinyl-7-nitro-9H-thioxanthen-9-one (6)
To a stirred solution of 2-(2-trimethylsilyl)ethinyl-7-nitro-9H-
thioxanthen-9-one (5) (147 mg, 0.416 mmol) in dry THF (10 mL)
and methanol (30 mL) heated to 60 ꢀC, NH4F (60 mg, 1.620
mmol) was added. The mixture was stirred in reflux for 2 h. After
cooling, the mixture was filtrated and the dark yellow precipitate
obtained washed with methanol and dried under reduced pres-
sure.
2-Cyano-7-nitro-9H-thioxanthen-9-one (7)
This compound was prepared from 2-amino-7-nitro-9H-thio-
xanthen-9-one (500 mg, 1.836 mmol) following the procedure
described in the literature.19 The cyano derivative (7) was
obtained as an orange powder. Yield: 64%. IR (KBr): n(CN)
Single crystals of 6, suitable for X-ray diffraction, were
obtained from a saturated THF solution, double layered with
2235, n(CO) 1643, n(NO2) 1518, 1343 cmꢁ1. H NMR (CDCl3):
1
7.60 (d, 1H, JHH ¼ 8.6, H4), 7.69 (dd, 1H, JHH ¼ 2.3, JHH ¼ 8.6,
ꢀ
methanol and stored at ꢁ4 C.
H3), 7.77 (d, 1H, JHH ¼ 8.8, H5), 8.45 (dd, 1H, JHH ¼ 2.5, JHH
¼
Yield: 84%. IR (KBr): n(CC) 2103, n(CO) 1639, n(NO2) 1517,
1
8.8, H6), 8.62 (d, 1H, JHH ¼ 2.2, H1), 9.45 (d, 1H, JHH ¼ 2.4, H8).
13C NMR (CDCl3): 125.67 (C8), 125.92 (C2), 126.23 (C6), 126.80
(CN), 127.56 (C3), 127.70 (C5), 129.08 (C9a), 129.66 (C8a),
129.75 (C1), 133.65 (C4), 134.04 (C4a), 134.12 (C10a), 143.73
(C7), 177.65 (C9).
1342 cmꢁ1. H NMR (CDCl3): 3.25 (s, 1H, CCH), 7.60 (d, 1H,
JHH ¼ 8.1, H3), 7.76 (d, 2H, JHH ¼ 8.7, H4, H5), 8.46 (d, 1H,
JHH ¼ 8.7, H6), 8.76 (s, 1H, H1), 9.46 (s, 1H, H8). 13C NMR
(CDCl3): 79.62 (C12), 92.77 (C11), 121.82 (C2), 125.63 (C8),
126.17 (C6), 126.42 (C3), 127.54 (C5), 128.38 (C9a), 129.34
(C4a), 132.83 (C8a), 133.48 (C1), 136.00 (C4), 143.24 (C10a),
146.06 (C7), 183.86 (C9).
X-Ray experimental details
Single-crystal X-ray structures for compounds 1 and 3 were
2-(4-Aminophenyl)sulfanyl-5-nitrobenzoic acid (2)
determined on an Enraf-Nonius TURBOCAD4 with rotative
ꢂ
anode using Cu-Ka radiation (l ¼ 1.5418 A), while for
This compound was prepared following a literature procedure.16
A mixture of 4-aminobenzenethiol (3 g, 24 mmol), 2-chloro-5-
nitrobenzoic acid (4.830 g, 24 mmol), anhydrous sodium
carbonate (2.540 g, 24 mmol) and copper powder (46 mg, 0.737
mmol) was refluxed in DMF. After 8 h, the mixture was poured
into 250 mL H2O and filtered. The filtrate was acidified with
dilute hydrochloric acid to give yellow precipitate. Recrystalli-
zation of 2 by cooling a heated supersaturated methanol solution
gave yellow crystals suitable for X-ray diffraction studies.
Yield: 68%. IR (KBr): n(NH2) 3494, 3397, n(OH) 3106, n(CO)
1691, n(NO2) 1509, 1342 cmꢁ1. 1H NMR [(CD3)CO]: 3.33 (s, 2H,
NH2), 6.86 (d, 2H, JHH ¼ 8.6, H1, H3), 7.04 (d, 2H, JHH ¼ 9, H5),
compound 6 diffraction data were obtained on an Enraf-Nonius
MACH3 diffractometer. Data for these compounds were
acquired at ambient temperature. All data were reduced and
corrected for Lorentzian, polarization and absorption effects
using XCAD4,32 XABS233 and DIFABS34 programs included in
WINGX-Version 1.70.01.35
Crystal structures of compounds 2 and 4 were determined at
room temperature on a Bruker AXS-KAPPA APEX II diffrac-
tometer with graphite-monochromated radiation (Mo Ka, l ¼
ꢂ
0.71069 A). All data were corrected for Lorentzian, polarization
and absorption effects using SAINT36 and SADABS37 programs.
SIR97,38 SIR200439 or SHELXS-9740 were used for structure
solution and SHELXL-9741 was used for structure refinement
using full matrix least-squares refinement on F2. All non-
hydrogen atoms were refined anisotropically. In compounds 1
and 2 all the hydrogen atoms were added in idealized positions
but allowing C–H distance to refine, in the COOH group the H
was added in an idealized position allowing the torsion angle to
refine from the electron density. The N–H distance was also
allowed to refine in compound 2. For compounds 3, 4 and 6 all
the hydrogens were added in idealized positions but in
compound 4 the N–H distance was allowed to refine. All the
graphic representations were done using ORTEP3,42
7.28 (d, 2H, JHH ¼ 8.6, H4, H9a), 8.19 (dd, 1H, JHH ¼ 2.5, JHH
¼
9, H6), 8.81 (d, 1H, JHH ¼ 2.5, H8). 13C NMR [(CD3)2CO]: 114.46
(C4a), 115.64 (C1, C3), 126.07 (C5,C6), 126.97 (C8a), 136.80
(C8), 137.20 (C4, C9a), 143.89 (C2), 150.74 (C10a), 155.71 (C7),
165.04 (C9).
2-Amino-7-nitro-9H-thioxanthen-9-one (4)
To mechanically stirred polyphosphoric acid (50 mL), heated to
70 ꢀC, 2-(4-aminophenyl)sulfanyl-5-nitrobenzoic acid (2.730 g,
9.401 mmol) was added. After addition, the temperature was
raised to 110 ꢀC and the reaction mixture was vigorously stirred
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RASTER3D43 and MERCURY 2.2.44 Table 3 summarizes the
crystallographic data for all the compounds.
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Acknowledgements
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20 H. G. O. Becker, W. Buger, G. Domschke, G. Fanghanel, J. Faust,
M. Ficher, F. Gentg, K. Gewald, R. Gluch, R. Nayer, K. Muller,
€
This work was supported in part by two research grant from
^
Fundac¸a˜o para a Ciencia e a Tecnologia (FCT), Portugal
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G. Zeppenfeld, Organikum, Quꢀımica Orga^nica Experimental,
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Projects PPCDT/QUI/58791/2004 and PTDC/QUI/65379/2006.
C. Jacob acknowledges FCT (PhD grant-SFRH/BD/14367/
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