Synthesis and Crystal Structures of Diaryl Thioethers and Aryl Benzyl Thioethers Derived from Thiosalicylic Acid

Article abstract of DOI:10.1007/s10870-018-0705-7

Abstract: Reaction of thiosalicylic acid and iodobenzene or 1-fluoro-2-nitrobenzene in the presence of two equiv. of K₂CO₃ in acetone–water afforded the according diaryl thioethers 1 and 2 bearing carboxyl groups. Treatment of thiosalicylic acid with benzyl bromide-type compounds under similar reaction conditions gave aryl benzyl thioethers 3–8 in excellent yields. Moreover, reactions of thiosalicylic acid and benzyl bromide in the presence of excess K₂CO₃ led to isolation of compound 9 (Leka et al. in Acta Cryst E69:o285–0286, 2013) through further esterification of the carboxyl group. Crystal structures of 2, 5–7 and 9 (Leka et al. in Acta Cryst E69:o285–0286, 2013), along with their spectroscopic properties are reported. Weak hydrogen-bonding interactions exist in compound 2 and isomers 5–7. Compounds 2 and 7 crystallize in the monoclinic space group P2₁/n and C2/c, respectively, with a = 12.04(3), b = 7.311(19), C=14.22(4) ?, β = 93.94(3)°, and Z = 4 for 2, and a = 14.934(13), b = 5.116(5), C=33.76(3) ?, β = 91.523(12)°, and Z = 8 for 7. The unit cell of 5 has triclinic P-1 symmetry with the cell parameters a = 5.4334(14), b = 7.7787(19), C=16.488(4) ?, α = 76.601(3)°, β = 86.078(3)°, γ = 70.772(3)°, and Z = 2 for 5. Compound 6 crystallizes in the orthorhombic space group Pbca with a = 15.1881(12), b = 7.3288(6), C=23.7366(19) ?, and Z = 8. Graphical Abstract: Reactions of thiosalicylic acid and a series of aryl- or benzyl halides in the presence of K₂CO₃ in acetone–water resulted in the formation of according diaryl thioethers and aryl benzyl thioethers in excellent yields.

Full text of DOI:10.1007/s10870-018-0705-7

Journal of Chemical Crystallography
https://doi.org/10.1007/s10870-018-0705-7
ORIGINAL PAPER
Synthesis and Crystal Structures of Diaryl Thioethers and Aryl Benzyl
Thioethers Derived from Thiosalicylic Acid
Dan Liu1 · Min Chen1 · Duowen Fang1 · Ai‑Quan Jia1 · Qian‑Feng Zhang1
Received: 19 June 2017 / Accepted: 23 March 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Reaction of thiosalicylic acid and iodobenzene or 1-fluoro-2-nitrobenzene in the presence of two equiv. of K2CO3 in ace-
tone–water afforded the according diaryl thioethers 1 and 2 bearing carboxyl groups. Treatment of thiosalicylic acid with
benzyl bromide-type compounds under similar reaction conditions gave aryl benzyl thioethers 3–8 in excellent yields.
Moreover, reactions of thiosalicylic acid and benzyl bromide in the presence of excess K2CO3 led to isolation of compound
9 (Leka et al. in Acta Cryst E69:o285–0286, 2013) through further esterification of the carboxyl group. Crystal structures
of 2, 5–7 and 9 (Leka et al. in Acta Cryst E69:o285–0286, 2013), along with their spectroscopic properties are reported.
Weak hydrogen-bonding interactions exist in compound 2 and isomers 5–7. Compounds 2 and 7 crystallize in the mono-
clinic space group P21/n and C2/c, respectively, with a=12.04(3), b=7.311(19), C=14.22(4) Å, β=93.94(3)°, and Z=4
for 2, and a = 14.934(13), b = 5.116(5), C=33.76(3) Å, β= 91.523(12)°, and Z = 8 for 7. The unit cell of 5 has triclinic
P-1 symmetry with the cell parameters a = 5.4334(14), b = 7.7787(19), C=16.488(4) Å, α = 76.601(3)°, β = 86.078(3)°,
γ = 70.772(3)°, and Z = 2 for 5. Compound 6 crystallizes in the orthorhombic space group Pbca with a= 15.1881(12),
b=7.3288(6), C=23.7366(19) Å, and Z=8.
Graphical Abstract
Reactions of thiosalicylic acid and a series of aryl- or benzyl halides in the presence of K2CO3 in acetone–water resulted in
the formation of according diaryl thioethers and aryl benzyl thioethers in excellent yields.
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10870-018-0705-7) contains
supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
Vol.:(0123456789)
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Journal of Chemical Crystallography
Keywords Thiosalicylic acid · Aryl sulfide · Synthesis · X-ray structure
aryl halides or benzyl halides in the presence of two equiv.
K2CO3 without a transition metal, as shown in Scheme 1,
and a thioether compound bearing a carboxylate group in
the presence of excess base that has also been isolated and
structurally characterized in this paper.
Introduction
In organic synthetic reactions, the scope and application
of organosulfur chemistry has increased remarkably since
sulfur-containing groups could serve as an important aux-
iliary function in synthetic sequences [1]. The preparation
of aryl sulfides constitutes an active area of organosulfur
chemistry due to the extensive biological and pharmaceuti-
cal applications of compounds containing Caryl–S bonds
[2, 3]. For example, aryl sulfide moieties are key compo-
nents of commercial pharmaceuticals, including Lansopra-
zole, Sulindac, Esomeprazole, and Quetiapine. As a result,
practical, cheap and efficient methods leading to Caryl–S
bond formation have attracted great attention [4–6]. Usu-
ally, synthesis of aryl sulfides involves the transition-
metal-catalyzed cross-coupling of aryl halides with thiols
with the assistance of a base [7, 8]. However, a number
of transition-metal-free reactions for aryl sulfide prepara-
tions have also been reported [9–11]. On the other hand,
thiosalicylic acid and its derivatives have received much
interest in recent years due to their potential application in
numerous disease treatments, in particular inflammatory,
allergic and respiratory diseases [12–14]. For instance,
copper(II) complexes with S-alkyl (alkyl=benzyl, methyl,
ethyl, propyl, butyl) derivatives of thiosalicylic acid dem-
onstrated moderate or selective antibacterial activity and
low antifungal activity [14]. Herein, we report the syn-
theses and crystal structures of both diaryl thioethers and
aryl benzyl thioethers by reacting thiosalicylic acid with
Experimental
General
All syntheses were carried out under nitrogen. Thiosalicylic
acid, iodobenzene, benzyl bromide, 2-bromobenzyl bromide,
2-methylbenzyl bromide, 3-methylbenzyl bromide, 4-meth-
ylbenzyl bromide, (1-bromoethyl)-benzene, 1-fluoro-2-ni-
trobenzene and potassium carbonate were purchased from
commercial sources and used without further purification.
Thioethers were synthesized according to literature meth-
ods [15]. 1H NMR spectra were recorded on a Bruker AM
400 spectrometer. Chemical shifts (δ, ppm) were reported
with reference to SiMe4 (1H). Infrared spectra (KBr) were
recorded on a Perkin-Elmer 16 PC FT-IR spectrophotometer
using KBr pellets. Gas chromatography analyses were per-
formed with an FID detector on a Shimadzu GC-2010 Plus
spectrometer using the RTX-5 column (15 m × 0.25 mm,
film thickness 0.25 µm). The initial temperature of the col-
umn was 110 °C and increased to 260 °C with a rate of
20 °C min−1.
1 3

Journal of Chemical Crystallography
COOH
S
I
2equiv. K2CO3
1
CH3COCH3-H2O
COOH
NO2
F
COOH
2equiv. K2CO3
S
SH
+
2
CH3COCH3-H2O
NO2
R1
COOH
R2
2equiv. K2CO3
S
Br
R2
CH3COCH3-H2O
R1
8
3
3: R1= H, R2 = H; 4: R1= H, R2 = 2-Br; 5: R1= H, R2 = 2-Me;
6: R1= H, R2 = 3-Me; 7: R1= H, R2 = 4-Me; 8: R1= Me, R2 = H
COOH
SH
COOH
O
O C
excess K2CO3
Br
S
+
+
S
CH3COCH3-H2O
3
9
Scheme 1 Syntheses of diaryl thioethers and aryl benzyl thioethers 1–9 derived from thiosalicylic acid
at room temperature over a period of 4 days. Yield: 89%.
Synthesis of 2‑Phenylsulfanyl‑benzoic Acid (1)
1
IR (cm−1): 3128, 1689 ν(–COOH). H NMR (acetone-
d6) δ (ppm): 7.25 (dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 7.40
(dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H), 7.52–7.61 (m, 4H), 8.01
(dd, J1 = 8.0 Hz, J2 = 1.2 Hz, 1H), 8.20 (dd, J1 = 8.0 Hz,
J2 =1.2 Hz, 1H).
A mixture of thiosalicylic acid (0.77 g, 5 mmol), iodoben-
zene (0.55 mL, 5 mmol), and K2CO3 (1.38 g, 10 mmol), in
water–acetone (20 mL, v/v=1:1) was stirred at reflux for 8 h.
After cooling and extraction with water (10 mL) and ethyl
acetate (10 mL), the aqueous phase was acidified to pH 7.0
with dilute HCl (1 M). The white precipitate was collected
by filtration and washed with water, then dried to yield com-
pound 1 as a white powder. Crystalline product of compound
1 was obtained by slow evaporation of a methanol–acetone
solution at room temperature over a period of 5 days. Yield:
86%. GC: purity 100%, tR = 6.252 min. IR (cm−1): 3120,
Synthesis of 2‑Benzylsulfanyl‑benzoic Acid (3)
The method was similar to that used for 1, employing benzyl
bromide (0.85 g, 5 mmol) instead of iodobenzene. Yield:
94%. GC: purity 100%, tR = 6.493 min. IR (cm−1): 3120,
1
1693 ν(–COOH), 834 ν(–CH2–S–). H NMR (acetone-
1
d6) δ (ppm): 4.23 (s, 2H, –CH2–S–), 7.21–7.52 (m, 8H),
1688 ν(–COOH). H NMR (acetone-d6) δ (ppm): 6.80 (d,
7.98–8.05 (m, 1H).
J=8.4 Hz, 1H), 7.22 (t, J=7.6 Hz, 1H), 7.32–7.36 (m, 1H),
7.49–7.57 (m, 5H), 8.00 (t, J=2.0 Hz, 1H).
Synthesis of 2‑(2‑Bromo‑benzylsulfanyl)‑benzoic
Acid (4)
Synthesis of 2‑(2‑Nitro‑phenylsulfanyl)‑benzoic Acid
(2)
The method was similar to that used for 1, employ-
ing 1-bromo-2-bromomethyl-benzene (1.25 g, 5 mmol)
instead of iodobenzene. Yield: 99%. GC: purity 100%,
tR = 7.437 min. IR (cm−1): 3124, 1689 ν(–COOH), 836
The method was similar to that used for 1, employing
1-fluoro-2-nitro-benzene (0.70 g, 5 mmol) instead of iodo-
benzene. Crystals suitable for X-ray analysis were grown by
slow evaporation of methanol–acetone solution (v:v=2:1)
1
ν(–CH2–S–). H NMR (acetone-d6) δ (ppm): 4.32 (s, 2H,
1 3

Journal of Chemical Crystallography
–CH2S–), 7.21–7.27 (m, 2H), 7.32–7.38 (m, 1H), 7.49–7.64
(m, 4H), 8.02 (dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H).
of iodobenzene. Crystals suitable for X-ray analysis were
grown by slow evaporation of methanol–acetone solution
(v:v = 2:1) at room temperature over a period of 5 days.
Yield: 85%. GC: purity 100%, tR = 7.143 min. IR (cm−1):
Synthesis of 2‑(2‑Methyl‑benzylsulfanyl)‑benzoic
Acid (5)
1
3120, 1688 ν(–COOH), 838 ν(–CH2–S–). H NMR (ace-
tone-d6) δ (ppm): 2.39 (s, 3H, –CH3) 4.25 (s, 2H, –CH2S–),
7.22–7.62 (m, 7H), 8.02 (dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H).
The method was similar to that used for 1, employing
1-bromomethyl-2-methyl-benzene (0.92 g, 5 mmol) instead
of iodobenzene. Crystals suitable for X-ray analysis were
grown by slow evaporation of methanol–acetone solution
(v:v = 2:1) at room temperature over a period of 4 days.
Yield: 90%. GC: purity 100%, tR = 7.147 min. IR (cm−1):
Synthesis of 2‑(4‑Methyl‑benzylsulfanyl)‑benzoic
Acid (7)
The method was similar to that used for 1, employing
1-bromomethyl-4-methyl-benzene (0.92 g, 5 mmol) instead
of iodobenzene. Crystals suitable for X-ray analysis were
grown by slow evaporation of methanol–acetone solution
(v:v = 2:1) at room temperature over a period of 4 days.
Yield: 86%. GC: purity 100%, tR = 7.145 min. IR (cm−1):
1
3118, 1687 ν(–COOH), 835 ν(–CH2–S–). H NMR (ace-
tone-d6) δ (ppm): 2.41 (s, 3H, –CH3) 4.26 (s, 2H, –CH2S–),
7.22–7.63 (m, 7H), 8.01 (dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H).
Synthesis of 2‑(3‑Methyl‑benzylsulfanyl)‑benzoic
Acid (6)
1
3120, 1686 ν(COOH), 832 ν(–CH2–S–). H NMR (ace-
tone-d6) δ (ppm): 2.40 (s, 3H, –CH3) 4.24 (s, 2H, –CH2S–),
7.22–7.62 (m, 7H), 8.02 (dd, J1 =8.0 Hz, J2 =1.2 Hz, 1H).
The method was similar to that used for 1, employing
1-bromomethyl-3-methyl-benzene (0.92 g, 5 mmol) instead
Table 1 Crystallographic data
Compound
2
5
6
7
9
and experimental details for 2,
5–7, and 9 [20]
CCDC number
Empirical formula
Formula weight
Crystal system
a (Å)
b (Å)
c (Å)
1556494
C13H9NO4S
275.27
Monoclinic
12.04(3)
7.311(19)
14.22(4)
90
93.94(3)
90
1248(6)
P21/n
1556495
C15H14O2S
258.32
Triclinic
5.4334(14)
7.7787(19)
16.488(4)
76.601(3)
86.078(3)
70.772(3)
640.0(3)
P-1
1828744
C15H14O2S
258.32
1828743
C15H14O2S
258.32
1556496
C21H18O2S
334.41
Orthorhombic Monoclinic
Triclinic
5.662(7)
11.988(15)
12.959(15)
72.796(15)
86.431(15)
89.971(15)
838.6(18)
P-1
15.1881(12)
7.3288(6)
23.7366(19)
90
90
90
2642.1(4)
Pbca
8
1.299
296(2)
1088
14.934(13)
5.116(5)
33.76(3)
90
91.523(12)
90
2578(4)
C2/c
8
1.331
296(2)
1088
0.241
6565
2352
0.2226
α(°)
β (°)
γ (°)
V (Å3)
Space group
Z
4
2
2
Dcalc (g cm−3
)
1.465
296(2)
568
0.268
6051
2675
0.0309
1.340
296(2)
272
0.243
3989
2838
0.0123
1.324
296(2)
352
0.203
5132
3648
0.0252
Temperature (K)
F(000)
µ(Mo-Kα) (mm−1
Total refln
)
0.236
15,685
2997
Independent refln
Rint
0.0360
R1a, wR2b (I>2σ(I)) 0.0495, 0.1432 0.0345, 0.0956 0.0377, 0.1142 0.0651, 0.1499 0.0541, 0.1325
R1, wR2 (all data)
0.1379, 0.2240 0.0411, 0.1014 0.0581, 0.1395 0.0881, 0.1815 0.1148, 0.1648
GoFc
1.210
1.048
0.861
0.878
1.009
∑
∑
aR1 =
Fo − Fc ∕
Fo
�
�
�
�
�
�
�
�
�
�
�
�
�
[
]
(
)
2
2
∑
∑
�
�
�
�
�
∕(Nobs − Nparam
�
2
2
2
1∕2
bwR2 =
w
F
− F
∕
w F
�
�
�
�
�
�
�
o
c
o
�
�
�
�
[
]
(
)
2
∑
�
�
�
�
2
1∕2
�
�
cGoF =
w
Fo − F
)
�
c
�
�
�
1 3

Journal of Chemical Crystallography
Fig. 1 a 2, showing the
atom-labelling scheme of one
molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at the 40% probabil-
ity level. b 2D framework of
2, projected along the crystal-
lographic b axis. O–H⋯O and
C–H⋯O hydrogen bonds are
shown as dashed lines
iodobenzene. Yield: 84%. GC: purity 100%, tR =6.621 min.
IR (cm−1): 3117, 1688 ν(–COOH), 835 ν(–CH2–S–).
1H NMR (acetone-d6) δ (ppm): 1.61 (d, J = 6.8 Hz, 3H,
–CH(CH3), 4.68 (q, J=6.8 Hz, 1H, –CH(CH3)), 7.18–7.50
(m, 8H), 7.89 (dd, J1 =8.0 Hz, J2 =1.6 Hz, 1H).
Synthesis of 2‑(1‑Phenyl‑ethylsulfanyl)‑benzoic Acid
(8)
The method was similar to that used for 1, employing
(1-bromo-ethyl)-benzene (0.92 g, 5 mmol) instead of
1 3

Journal of Chemical Crystallography
Fig. 2 a The content of 5, show-
ing the atom-labeling scheme of
one molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at the 40% prob-
ability level. b View showing
the formation of the centrosym-
metric dimer through O–H⋯O
hydrogen bonds in the molecu-
lar packing projected along the
crystallographic a axis
X-ray analysis were grown by slow evaporation of metha-
nol–acetone solution (v:v=2:1) at room temperature over a
period of 5 days. The crystal structure of this compound has
been reported previously [20] and is included for the sake of
comparison only. Yield: 49%. IR (cm−1): 1720 ν(–COOR),
Synthesis of 2‑Benzylsulfanyl‑benzoic Acid Benzyl
Ester (9)
A mixture of thiosalicylic acid (0.77 g, 5 mmol), benzyl
bromide (0.85 g, 5 mmol), and K2CO3 (1.38 g, 20 mmol),
in water–acetone (20 mL, v/v=1:1) was stirred at reflux for
24 h. After cooling overnight, colorless crystals precipitated.
The crystals were collected by filtration and washed with
water, then dried to yield compound 9. Crystals suitable for
1
838 ν(–CH2–S–). H NMR (acetone-d6) δ (ppm): 4.23 (s,
2H, –CH2S–), 4.30 (s, 2H, –CH2O–), 7.20–7.54 (m, 13H),
7.98–8.07 (m, 1H).
1 3

Journal of Chemical Crystallography
Fig. 3 a The content of 6, show-
ing the atom-labeling scheme of
one molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at the 40% prob-
ability level. b View showing
the formation of the centrosym-
metric dimer through O–H⋯O
hydrogen bonds in the molecu-
lar packing projected along the
crystallographic b axis
X‑ray Crystallography
Results and Discussion
Crystallographic data and experimental details for 2, 5–7
and 9 [20] are summarized in Table 1. Intensity data were
collected on a Bruker SMART APEX 2 CCD diffractom-
eter using graphite-monochromated Mo–Kα radiation
(λ = 0.71073 Å) at 296(2) K. The collected frames were
processed with the software SAINT [16]. The data was
corrected for absorption using the program SADABS [17].
Structures were solved by the direct methods and refined by
full-matrix least-squares on F2 using the SHELXTL software
package [18]. All non-hydrogen atoms were refined aniso-
tropically. The carboxylic acid hydrogens in compounds 2,
5, 6 and 7 are located in the diffraction maps. The positions
of all other hydrogen atoms were generated geometrically
(Csp3–H=0.96 Å and Csp2–H=0.93 Å), assigned isotropic
thermal parameters, and allowed to ride on their respective
parent carbon atoms before the final cycle of least-squares
refinement.
As shown in Scheme 1, reactions of thiosalicylic acid and
iodobenzene or 1-fluoro-2-nitro-benzene in the presence
of two equiv. of K2CO3 in acetone–water at reflux for 8 h
afforded crystalline solid diaryl thioethers 1 and 2 in good
yields. Treatment of thiosalicylic acid with benzyl bromide
or the bromo/methyl substituted benzyl bromide compounds
under the same conditions afforded corresponding aryl ben-
zyl thioether derivatives 3–8 in excellent yields (85–99%).
Similar reactions of thiosalicylic acid with benzyl bromide
in the presence of excess K2CO3 gave benzyl 2-(benzylsul-
fanyl)benzoate 9 through further esterification of the car-
boxyl group. Compared to the previously reported reaction
between thiosalicylic acid and 1-chloro-2-nitro-benzene
to synthesize compound 2, the yield is improved from 53
to 89% in this report [15]. Moreover, a similar compound,
2-(2-methoxyphenylsulfanyl)-benzoic acid, was synthesized
by an alternative method, from reactions of 2-methoxythio-
phenol and 2-chlorobenzoic acid with K2CO3 as the base
and copper as the catalyst [19]. It is noted that compound
9 has already been synthesized and characterized by an
1 3

Journal of Chemical Crystallography
Fig. 4 a The content of 7, show-
ing the atom-labeling scheme of
one molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at the 40% prob-
ability level. b View showing
the formation of the centrosym-
metric dimer through O–H⋯O
hydrogen bonds in the molecu-
lar packing projected along the
crystallographic b axis
alternative method using thiosalicylic acid to react with two
equiv. of benzyl halogenide in the presence of two equiv. of
NaOH [20]. The infrared spectra of thioether compounds
1–8 with carboxyl groups showed –CO2H peaks at about
3120 and 1690 cm−1, and for ester derivative 9 showed a
–CO2R peak at about 1720 cm−1. The aryl benzyl thioethers
3–9 showed –CH2–S– or –CH(CH3)–S-peaks at around
5–7 have almost the same retention time (7.143–7.147 min)
indicating that o-, m-, or p-positions of a methyl group have
little effect on the retention time of similar compounds.
Molecular structures of compounds 2, and 5–7 were fur-
ther confirmed by single-crystal X-ray diffraction analysis, as
shown in Figs. 1, 2, 3, 4 and 5, respectively. Selected bond
lengths and angles are given in Tables 2, 3, 4, 5 and 6, while
the hydrogen-bond characteristics and geometric parameters
for 2, 5, 6 and 7 are summarized in Table 7. The C(7)–S(1)
bond length is 1.779(6) Å in 2, which lies well in the range of
those in analogous compounds, 2-(2-methoxyphenylsulfanyl)-
benzoic acid (1.782 Å) [19], 2-[2-(hydroxy-isopropoxy-
phosphoryl)-phenylsulfanyl]-benzoic acid (1.774 Å) [23],
2-(4-trifluoromethyl-phenylsulfanyl)-benzoic acid (1.782 Å)
[24], and the same structure reported by Reinke (1.789 Å)
[25]. In aryl benzyl thioether isomers 5–7, the CAr–S bond
1
835 cm−1 [21]. The H NMR spectra of compounds 3–7
and 9 all showed –CH2–S– protons as a single peak ranging
from 4.23 to 4.32 ppm, which are comparable to those in
related compounds [22]. The signal of a –CH(CH3)–S– pro-
ton showed a quartet at 4.68 ppm with J = 6.8 Hz, while
the –CH(CH3)–S– protons showed a doublet at 1.61 ppm
with J=6.8 Hz. GC analysis showed that the retention time
of aryl benzyl thioethers 3–8 (6.493–7.437 min) was longer
than that of diaryl thioether 1 (6.252 min), and the isomers of
1 3

Journal of Chemical Crystallography
Fig. 5 a Molecular structure
of 9 [20], showing the atom-
labeling scheme. Displacement
ellipsoids are drawn at the 40%
probability level. b Packing
mode of compound 9, projected
along the crystallographic c axis
Table 2 Selected bond lengths (Å) and angles (°) for 2
Table 3 Selected bond lengths (Å) and angles (°) for 5
S(1)–C(7)
C(1)–O(1)
N(1)–O(3)
C(1)–C(2)
C(7)–S(1)–C(8)
O(3)–N(1)–O(4)
1.779(6)
1.313(5)
1.204(5)
1.473(5)
101.62(15)
123.6(4)
S(1)–C(8)
C(1)–O(2)
N(1)–O(4)
N(1)–C(13)
O(1)–C(1)–O(2)
1.784(5)
1.218(5)
1.187(5)
1.477(6)
123.4(4)
S(1)–C(7)
C(1)–O(1)
C(8)–C(9)
C(7)–S(1)–C(8)
C(9)–C(8)–S(1)
1.7707(14) S(1)–C(8)
1.3140(17) C(1)–O(2)
1.8275(15)
1.2221(17)
1.480(2)
1.507(2)
102.28(7)
108.39(10)
C(1)–C(2)
O(1)–C(1)–O(2)
122.33(14)
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Journal of Chemical Crystallography
Table 4 Selected bond lengths (Å) and angles (°) for 6
bond length (1.192(3) Å) in carboxylate compound 9 [20].
In diaryl thioether 2, the carboxylic acid group (C2/C1/O2/
O1) is twisted by 15.5(2)° from the mean plane of the adja-
cent benzene ring (C2–C7), similar to that in 2-(4-trifluoro-
methyl-phenylsulfanyl)-benzoic acid (13.6(7)°) [24]. While
in aryl benzyl thioether molecules 5–7 and 9, the carboxylic
acid group are twisted by 2.5(1)° for 5, 5.4(1)° for 6, and
2.5(2)° for 7, and 3.2(2)° for 9 [20] from the mean plane
of C2–C7. In compound 2, the two phenyl ring planes are
roughly perpendicular (86.0(2)o), similar to that in 2-(4-trif-
luoromethyl-phenylsulfanyl)-benzoic acid (88.7(2)°) [24], but
larger than that in 2-(2-methoxyphenylsulfanyl)-benzoic acid
(78.50(12)°) [19], suggesting the free rotation of the S-phenyl
ring around the single bonds of the C(7)–S(1)–C(8) fragment.
In aryl benzyl thioether molecules 5–7, the dihedral angles
between the mean planes of the phenyl rings are 74.5 (1)° for
5, 87.0(1)° for 6 and 78.3(1)° for 7. In compound 9 [20], the
dihedral angle between the central thiosalicylic ring C2–C7
and terminal O-benzyl group is 5.8(2)° indicating a nearly co-
planar orientation of these two fragments. On the other hand,
the ring of the S-benzyl group is significantly twisted with
respect to the central ring C2–C7 forming a dihedral angle of
71.6(1)°. The dihedral angle between the peripheral phenyl
rings in 9 is 65.78(10)°, as expected similar to that in benzyl
2-(benzylsulfanyl)benzoate reported by Leka (66.16(6)°) [20].
The packing view of compound 2 along the ac plane is
shown in Fig. 1b. Crystal packing in molecule 2 is gov-
erned by the weak intermolecular C–H⋯O(NO2) and
O–H⋯O hydrogen-bonding interactions (Table 7). In the
crystal structure of 2, the H-bonded layers are parallel to
(1 0 −1) (Fig. 1). The separation of H(1)⋯O(2) is 1.92(5)
Å and the angle of O(1)–H(1)⋯O(2) is 167(5)° in com-
pound 2, and comparable with those in the molecules of
2-(4-trifluoromethyl-phenylsulfanyl)-benzoic acid (1.86 Å,
175°) [24] and 2-(2-methoxyphenylsulfanyl)-benzoic acid
(1.85 Å, 171°) [19]. In compounds 5–7, symmetry equiva-
lent molecules related by a crystallographic inversion center
are linked by O–H⋯O hydrogen bonds, forming centrosym-
metric dimers as shown in Figs. 2b, 3b and 4b, respectively.
The separation of H(1)⋯O(2) is 1.79(3) Å and the angle
of O(1)–H(1)⋯O(2) is 174(2)° for 5, similar to those in its
isomers 6 (1.74(3) Å, 176(3)°) and 7 (1.78(5) Å, 167(5)°).
S(1)–C(7)
C(1)–O(1)
C(8)–C(9)
1.7640(19) S(1)–C(8)
1.822(2)
1.222(2)
1.474(3)
1.318(2)
1.508(3)
C(1)–O(2)
C(1)–C(2)
C(7)–S(1)–C(8)
C(9)–C(8)–S(1)
103.64(9)
105.72(13)
O(1)–C(1)–O(2)
121.98(18)
Table 5 Selected bond lengths (Å) and angles (°) for 7
S(1)–C(7)
C(1)–O(1)
1.759(3)
1.303(3)
S(1)–C(8)
C(1)–O(2)
1.808(3)
1.217(3)
1.477(4)
122.5(3)
C(8)–C(9)
C(7)–S(1)–C(8)
C(9)–C(8)–S(1)
1.498(4)
102.26(14)
108.7(2)
C(1)–C(2)
O(1)–C(1)–O(2)
Table 6 Selected bond lengths (Å) and angles (°) for 9 [20]
S(1)–C(7)
C(1)–O(1)
1.732(3) S(1)–C(8)
1.317(3) C(1)–O(2)
1.797(3)
1.192(3)
1.489(4)
1.474(4)
122.4(2)
C(15)–O(1)
C(8)–C(9)
1.434(3) C(15)–C(16)
1.479(4) C(1)–C(2)
C(7)–S(1)–C(8)
O(1)–C(15)–C(16) 108.9(2)
103.26(12) O(1)–C(1)–O(2)
C(16)–C(15)–S(1) 107.68(18)
lengths are 1.7707(14), 1.7640(19) and 1.759(3) Å, respec-
tively, a little shorter than the corresponding CBn–S bond
lengths [1.8275(15) Å for 5, 1.822(2) for 6, 1.808(3) Å for
7]. The CAr–S and CBn–S bond lengths are 1.732(3) and
1.797(3) Å, respectively in 9, which are slightly shorter than
those in the known compound benzyl 2-(benzylsulfanyl)ben-
zoate reported by Leka (1.7623(19), 1.8159(18) Å) [20]. The
CAr–S–CAr bond angle is 101.57(14)° in diaryl thioether 2,
which is near to those in aryl benzyl thioethers 5 (102.28(7)°),
6 (103.64(9)°), 7 (102.26(14)°) and 9 (103.26(12)°). As
expected, the C–O bond lengths (1.303(3)–1.318(2) Å) are a
little longer than the C=O bond lengths (1.217(3)–1.2221(17)
Å) in carboxylic acid compounds 2, 5, 6 and 7. Similarly,
the C–O bond length of 1.317(3) Å is longer than the C=O
Table 7 Hydrogen-bonding
Compound
D–H⋯A
d(D–H) (Å)
d(H⋯A) (Å)
d(D⋯A) (Å)
∠(DHA) (deg)
system for 2, and 5–7
2
O(1)–H(1)⋯O(2)i
C5A–H5AO4D
0.76(5)
0.930
0.89(2)
0.91(3)
0.90(5)
1.92(5)
2.543
1.79(3)
1.74(3)
1.78(5)
2.664(6)
3.211
2.6734(17)
2.649(2)
2.661(3)
167(5)
129.1
174(2)
176(3)
167(5)
5
6
7
O(1)–H(1)⋯O(2)ii
O(1)–H(1)⋯O(2)iii
O(1)–H(1)⋯O(2)iv
Symmetry codes: (i) −x+1, −y+3, −z+1; (ii) −x−1, −y+2, −z; (iii) −x+1, −y+3, −z+1; (iv)
−x+2, −y−1, −z+1
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Journal of Chemical Crystallography
3. Wagner AM, Sanford MS (2014) J Org Chem 79:2263–2267
4. Fernández-Rodríguez MA, Shen Q, Hartwig JF (2006) J Am
Chem Soc 128:2180–2181
No obvious hydrogen bonding interactions were found in the
carboxylate compound 9 [20].
In summary, a series of diaryl thioethers and aryl benzyl
thioethers were synthesized in excellent yields and charac-
terized by single-crystal X-ray diffraction along with spec-
troscopic methods, in which a thioether compound with the
ester group, 2-benzylsulfanyl-benzoic acid benzyl ester, was
isolated from reactions of thiosalicylic acid and benzyl bro-
mide in the presence of excess K2CO3. The dihedral angle
of two phenyl rings in diaryl thioether 2 (86.0(2)o) is com-
parable to those in aryl benzy thioethers 5–7 (74.5(1)° for 5,
87.0(1)° for 6 and 78.3(1)° for 7) and 9 (71.6(1)°) [20]. The
carboxylic acid group (C2/C1/O2/O1) is twisted by 15.5(2)°
from the mean plane of the adjacent phenyl ring (C2–C7) in
diaryl thioether 2, larger than those in aryl benzyl thioethers
5–7 and 9 (2.5(1)°–5.4(1)°) [20]. In the crystal structures of
5–7, symmetry equivalent molecules are linked by O–H⋯O
hydrogen bonds, forming centrosymmetric dimers [19],
whereas the crystal packing in 2 displays a hydrogen-bonded
two-dimensional framework displaying different types of
O–H⋯O and C–H⋯O(NO2) hydrogen bonds.
5. Firouzabadi H, Iranpoor N, Samadi A (2014) Tetrahedron Lett
55:1212–1217
6. Zhang C, McClure J, Chou CJ (2015) J Org Chem 80:4919–4927
7. Arisawa M, Suzuki T, Ishikawa T, Yamaguchi MJ (2008) J Am
Chem Soc 130:12214–12215
8. Wang X, Cuny GD, Noel T (2013) Angew Chem Int Ed
52:7860–7864
9. Wang B, Graskemper JW, Qin L, DiMagno SG (2010) Angew
Chem Int Ed 49:4079–4083
10. Cheng J, Ramesh C, Kao H, Wang Y, Chan C, Lee C (2012) J
Org Chem 77:10369–10374
11. Liu ML, Ren P, Shi W, Cui JZ, Cheng P, Gao HL (2011) Inorg
Chim Acta 378:56–65
12. Miloš VN, Marina ŽM, Verica VJ, Zoran RR, Ivana DR, Ljiljana
R, Sladana BN, Goran AB, Srećko RT, Gordana PR (2014) Poly-
hedron 79:80–87
13. Bernardelli P, Cronin AM, Denis A, Denton SM, Jacobelli H,
Kemp MI, Lorthiois E, Rousseau F, Serradeil-Civit D, Vergne F
(2005) US Patent 20050267095
14. Bukonjić AM, Tomović DL, Nikolić MV, Mijajlović MZ, Jevtić
VV, Ratković ZR, Novaković SB, Bogdanović GA, Radojević ID,
Maksimović JZ, Vasić SM, Comić LR, Trifunović SR, Radić GP
(2017) J Mol Struct 1128:330–337
15. Xin S, Du XJ, Wang Y, Sun QZ (2010) 146 Academic confer-
ence of fine chemical Specialized Committee of China Chemical
Society, the third National Symposium on technical and economic
development of clean chemical production technology
16. SMART and SAINT+ for Windows NT Version 6.02a; Bruker
Analytical X-ray Instruments Inc. Madison 1998
17. Sheldrick GM (1996) SADABS. University of Göttingen,
Göttingen
Supplementary material
Crystallographic data for 2, 5–7 and 9 [20] has been depos-
ited with the Cambridge Crystallographic Data Centre as
supplementary publication nos. CCDC 1556494, 1556495,
1828744, 1828743, and 1556496 respectively. Copies of the
data can be obtained free of charge on application to CCDC,
12 Union Road, Cambridge CB2 1EZ, UK [fax: (+44)1233-
336-033; e-mail: deposit@ccdc.cam.ac.uk].
18. Sheldrick GMSHELXTL (1997) Software reference manual, ver-
sion 5.1. Bruker AXS Inc., Madison
19. Li A-J, Tao M-L, Ma J, Zhou X-Q, Liu D-Z (2006) Acta Cryst
E62:o1176–o1177
20. Leka Z, Novaković SB, Bogdanović GA, Radić GP, Ratković ZR
(2013) Acta Cryst E69:o285–o286
21. Zhang X-Y, Song H-B, Li Q-S, Liu X-F, Tang L-F (2007) Poly-
hedron 26:3743–3749
Acknowledgements This project was supported by the Natural Science
22. Huynh HV, Seidel WW, Lügger T, Roland F, Wibbeling B, Hahn
FE (2002) Z Naturforsch 57:1401–1408
Foundation of China (21201003, 21372007).
23. Hamel M, Rizzato S, Lecinq M, Sène A, Vazeux M, Gulea M,
Albinati A, Kozelka J (2007) Chem Eur J 13:5441–5449
24. Yamuna TS, Jasinski JP, Anderson BJ, Yathirajan HS, Kaur M
(2013) Acta Cryst E69:o1704–o1177
References
25. Reinke H, Potter M, Dehne H (2008) Private communication
(CCDC 705285)
1. Kondo T, Mitsudo T (2000) Chem Rev 100:3205–3220
2. Rakitin OA (2007) Sci Synth 31a:975–1000
Affiliations
Dan Liu1 · Min Chen1 · Duowen Fang1 · Ai‑Quan Jia1 · Qian‑Feng Zhang1
1
* Ai-Quan Jia
jaiquan@ahut.edu.cn
Institute of Molecular Engineering and Applied Chemistry,
Anhui University of Technology, Ma’anshan 243002, Anhui,
People’s Republic of China
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