Syntheses and Crystal Structures of Benzyl Substituted Thiazolidin-2-cyanamide Derivatives

Article abstract of DOI:10.1007/s10870-020-00827-4

Abstract: Reaction of thiazolidin-2-cyanamide and substituted benzyl bromide compounds in acetonitrile at room temperature afforded the 3-(2′-substituted benzyl)thiazolidin-2-cyanamide derivatives 1–13 in good yields. Compounds 1–13 were characterized by proton nuclear magnetic resonance (¹H NMR) and infrared spectroscopies, of which the structures of the isomeric o-, m-, and p-fluoro derivatives 4–6 were established by single crystal X-ray crystallography. Compound 4 crystallizes in the monoclinic space group P2₁/n, with a = 9.177(19), b = 8.551(18), c = 14.090(3) ?, β = 98.243(3)°, and Z = 4. The unit cell of 5 has a monoclinic P2₁/c symmetry with the cell parameters a = 9.289(2), b = 14.057(4), c = 8.574(2) ?, β = 100.350(3)°, and Z = 4. The unit cell of 6 also has a monoclinic P2₁/c symmetry with the cell parameters a = 9.333(4), b = 14.034(5), c = 8.508(3) ?, β = 99.15(5)°, and Z = 4. Graphic Abstract: A series of 3-(2′-substituted benzyl)thiazolidin-2-cyanamide derivatives were efficiently synthesized via the reaction of benzyl bromide compounds with thiazolidin-2-cyanamide, of which the structures of the isomeric o-, m-, and p-fluoro derivatives were characterized by X-ray crystallography. [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10870-020-00827-4

Journal of Chemical Crystallography
https://doi.org/10.1007/s10870-020-00827-4
ORIGINAL PAPER
Syntheses and Crystal Structures of Benzyl Substituted
Thiazolidin‑2‑cyanamide Derivatives
Jun‑Ling Wang1 · Sen Ma1 · Ai‑Quan Jia1 · Qian‑Feng Zhang1
Received: 4 November 2019 / Accepted: 27 February 2020
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract
Reaction of thiazolidin-2-cyanamide and substituted benzyl bromide compounds in acetonitrile at room temperature aforded
the 3-(2′-substituted benzyl)thiazolidin-2-cyanamide derivatives 1–13 in good yields. Compounds 1–13 were characterized
by proton nuclear magnetic resonance (1H NMR) and infrared spectroscopies, of which the structures of the isomeric o-,
m-, and p-fuoro derivatives 4–6 were established by single crystal X-ray crystallography. Compound 4 crystallizes in the
monoclinic space group P21/n, with a=9.177(19), b=8.551(18), c=14.090(3) Å, β = 98.243(3)°, and Z=4. The unit cell
of 5 has a monoclinic P21/c symmetry with the cell parameters a=9.289(2), b=14.057(4), c=8.574(2) Å, β = 100.350(3)°,
and Z=4. The unit cell of 6 also has a monoclinic P21/c symmetry with the cell parameters a =9.333(4), b=14.034(5),
c=8.508(3) Å, β = 99.15(5)°, and Z=4.
Graphic Abstract
A series of 3-(2′-substituted benzyl)thiazolidin-2-cyanamide derivatives were efciently synthesized via the reaction of benzyl
bromide compounds with thiazolidin-2-cyanamide, of which the structures of the isomeric o-, m-, and p-fuoro derivatives
were characterized by X-ray crystallography.
Keywords Thiazolidin-2-cyanamide · Synthesis · Crystal structure · Hydrogen bond
Introduction
As known, thiacloprid (3-(6-chloropyridin-3-ylmethyl)-thi-
* Qian-Feng Zhang
azolidin-2-ylidene cyanamide) is a novel chlorinated broad-
spectrum nicotinic insecticide agent with high efciency and
low toxicity, developed in the 1990s by Bayer Agrochemical
Company of Germany and Bayer Agrochemical Company
zhangqf@ahut.edu.cn
1
Institute of Molecular Engineering and Applied Chemistry,
Anhui University of Technology, Ma’anshan 243002, Anhui,
People’s Republic of China
Vol.:(0123456789)
1 3

Journal of Chemical Crystallography
of Japan as a new type of bio-pesticide [1]. Therefore, how
to develop thiacloprid at a lower cost and how to modify
its structure to achieve drug improvement has become a
research hotspot at present [2, 3]. It is well known that thia-
zolidin-2-cyanamide is an important substrate in the synthe-
ses of thiacloprid and its derivatives [4]. For examples, the
compounds synthesized by the reaction of thiazolidin-2-cy-
anamide and acid chloride have good antifungal activity [5].
A related phenyl oxazol-based neonicotinoid derivative with
thiazolidin-2-ylidene-cyanamide moiety is reported to have
moderate insecticidal activity against pea aphids, and favora-
ble fungicidal activities and anti-tumor activities [6]. Moreo-
ver, the phenyl furyl-based thiazolidin-2-cyanamide deriva-
tives showed bioactivity against type III secretion system of
Xanthomonas oryzae on rice [7]. Syntheses and structures
of N-[(Z)-3-(4-chlorobenzoyl)-1,3-thiazolidin-2- ylidene]
cyanamide and (Z)-N-[3-(4-bromobenzoyl)-1,3-thiazolidin-
2-ylidene]- cyanamide were also reported, showing that the
typical dihedral angle between the benzene and thiazolidine
rings is about 63.0° [8, 9]. Herein, we report the syntheses
of thiacloprid analogues by using various substituted ben-
zyl bromide compounds instead of chloromethylpyridine to
react with thiazolidin-2-cyanamide (see Scheme 1).
recorded on a Bruker AV400-MHz Advance NMR spec-
trometer at 400 MHz.
General Synthetic Route for Substituted Thiacloprid
Derivatives
Thiazolidin-2-ylidene-cyanamide (0.317 g, 2.50 mmol) in
acetonitrile (20 mL) was dropwise added to a stirred solution
of substituted benzyl bromide (2.5 mmol) and 14 mL NaOH
aqueous solution (1 M). The mixture is stirred at room tem-
perature for 8–10 h. The soild was collected by fltration,
washed with n-hexane and dried in vacuo.
3-(2-methylbenzyl)thiazolidin-2-ylidene-cyanamide (1)
1
white solid, yield: 0.494 g (85.4%), m.p.: 115–16 °C. H
NMR (400 MHz, CDCl3): δ (ppm) 2.34 (s, 3H, CH3), 3.32 (t,
J=7.6 Hz, 2H, NCH2), 3.74 (t, 2H, J=7.6 Hz, SCH2), 4.57
(s, 2H, CH2), 7.14–7.19 (m, 2H, Ph). IR (KBr disc, cm−1):
2918, w, ν(CH); 2182, s, 2160 sh, v(C≡N); 1573, s, v(C=N).
3-(3-methylbenzyl)thiazolidin-2-ylidene-cyanamide (2)
white solid, yield: 0.664 g (89.7%), m.p.: 126–128 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 3.37 (t, J=7.6 Hz, 2H,
NCH2), 3.82 (t, J=7.6 Hz, 2H, SCH2), 4.76 (s, 2H, CH2),
7.19–7.24 (m, 1H, Ph), 7.32–7.36 (m, 2H, Ph), 7.59–7.60
(m, 1H, Ph). IR (KBr disc, cm−1): 3012, w, ν(CH); 2181, s,
2152 sh, v(C≡N); 1573, s, v(C=N).
Experimental
3-(4-methylbenzyl)thiazolidin-2-ylidene-cyanamide (3)
white solid, yield: 0.529 g (87.4%), m.p.: 120–121 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 3.41 (t, J=7.6 Hz, 2H,
NCH2), 3.80 (t, J=7.6 Hz, 2H, SCH2), 4.65 (s, 2H, CH2),
7.52–7.49 (m, 1H, Ph), 7.55 (dd, J=5.7, 4.1 Hz, 2H, Ph),
7.65 (dt, J=7.3, 1.6 Hz, 1H, Ph). IR (KBr disc, cm−1): 2916,
w, ν(CH); 2182, s, 2146 sh, v(C≡N); 1570, s, v(C=N).
3-(2-fuorobenzyl)thiazolidin-2-ylidene-cyanamide (4)
white solid, yield: 0.492 g (83.6%), m.p.: 105–106 °C.
1HNMR (400 MHz, CDCl3): δ (ppm) 3.36–3.39 (t,
J=7.6 Hz, 2H, NCH2), 3.78 (t, J=7.6 Hz, 2H, SCH2), 4.61
(s, 2H, CH2), 6.96–7.06 (m, 3H, Ph), 7.26–7.37 (m, 1H,
Ph). IR (KBr disc, cm−1): 3056, w, ν(CH); 2182, s, 2151 sh
v(C≡N); 1568, s, v(C=N).
General Procedure
All solvents were purifed by routine procedures and distilled
under an atmosphere of dry nitrogen before use. 2-Meth-
ylbenzyl bromide, 3-methylbenzyl bromide, 4-methylben-
zyl bromide, 2-cyanobenzyl bromide, 3-cyanobenzyl bro-
mide, 4-cyanobenzyl bromide, 2-fluorobenzyl bromide,
3-fuorobenzyl bromide, 4-fuorobenzyl bromide, 2-bro-
mobenzyl bromide, benzylbromide and 4-chlorobenzyl bro-
mide were purchased from Alfa Aesar Ltd. and used without
further purifcation. Thiazolidin-2-ylidene-cyanamide was
synthesized according to literature methods [10, 11]. The
infrared spectra were recorded on a Digilab FTS-40 spectro-
photometer with use of pressed KBr pellets. For IRs, labels
with s (strong), m(medium), w (weak), sh (shoulder), br
(broad) are reported for each band. 1H-NMR spectra were
3-(3-fuorobenzyl)thiazolidin-2-ylidene-cyanamide (5)
yellow solid, yield: 0.494 g (84.9%), m.p.: 101–102 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 3.35 (t, J=7.6 Hz, 2H,
NCH2), 3.75 (t, J=7.6 Hz, 2H, SCH2), 4.58 (s, 2H, CH2),
7.05 (m, 2H, Ph), 7.22–7.29 (m, 1H, Ph), 7.29–7.24 (m, 1H,
Ph). IR (KBr disc, cm−1): 2987, w, ν(CH); 2178, s, 2149 sh
v(C≡N); 1571, s, v(C=N).
3-(4-fuorobenzyl)thiazolidin-2-ylidene-cyanamide (6)
yellow solid, yield: 0.528 g (87.2%), m.p.: 109–110 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 3.35 (t, J=7.6 Hz, 2H,
NCH2), 3.75 (t, J=7.6 Hz, 2H, SCH2), 4.68 (s, 2H, CH2),
7.01–7.09 (m, 2H, Ph), 7.28–7.24 (m, 2H, Ph). IR (KBr disc,
Scheme 1 Structure of thiacloprid
1 3

Journal of Chemical Crystallography
Table 1 Crystallographic data
and details for compounds 4, 5
and 6 with estimated standard
deviations in parentheses
Compound
4
5
6
Empirical formula
Formula weight
Crystal system
Space group
a (Å)
b (Å)
c (Å)
C11H10N3FS
235.28
Monoclinic
P21/n
9.177 (19)
8.551 (18)
14.090 (3)
98.243 (3)
1094.3 (4)
4
C11H10N3FS
235.28
Monoclinic
P21/c
9.289 (2)
14.057 (4)
8.574 (2)
100.350 (3)
1101.4 (5)
4
C11H10N3FS
235.28
Monoclinic
P21/c
9.333 (4)
14.034 (5)
8.508 (3)
99.15 (5)
1100.2 (7)
4
β (°)
V(Å3)
Z
Dcalc (Mg m−3
)
1.428
1.419
1.420
Crystal size (mm3)
Temperature (K)
F(000)
0.11×0.14×0.16
0.10×0.13×0.18
0.12×0.14×0.19
296 (2)
488
0.283
296 (2)
488
0.281
296 (2)
488
0.282
μ(Mo-Kα) (mm−1
Total refn
)
6504
6577
6704
Independent refn, I>2σ
Rint
2470, 1868
0.0250
2481, 1632
0.0307
2503, 1596
0.0352
Parameters
145
145
145
R1a, wR2b (I>2σ(I))
R1, wR2 (all data)
GoFc
0.0419, 0.1122
0.0558, 0.1213
1.055
0.0426, 0.0941
0.0731, 0.1082
1.008
0.0433, 0.1029
0.0754, 0.1187
1.045
aR1=|||Fo|–|Fc||/|Fo|
2
2
2 2 1/2
bwR2=[w(|Fo |–|Fc |)2/w|Fo | ]
cGoF=[w(|Fo|–|Fc|)2/(Nobs–Nparam)]1/2
Scheme 2 Synthesis of
3-(2′-substituted benzyl)thiazo-
lidin-2-cyanamide derivatives
1 3

Journal of Chemical Crystallography
Fig. 1 a Structure of 4, showing
the atom-labelling scheme of
one molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at 30% probability
level and H atoms are shown as
small spheres of arbitrary radii.
The crystal structure of (b),
viewed along the a axis. Dashed
lines indicate C–H…F hydrogen
bonds
cm−1): 2963, w, ν(CH); 2180, s, 2143 sh v(C≡N); 1580, s,
v(C=N).
3-(3-cyanobenzyl)thiazolidin-2-ylidene-cyanamide (8)
white solid, yield: 0.498 g (86.1%), 128–129 °C. 1H NMR
(400 MHz, CDCl3): δ (ppm) 2.35 (s, 3H, CH3), 3.34 (t,
J=7.6 Hz, 2H, NCH2), 3.73–3.77 (t, J=7.6 Hz, 2H, SCH2),
4.56 (s, 2H, CH2), 7.03–7.27 (m, 4H, Ph). IR (KBr disc,
cm−1): 2917 w, ν(CH); 2180, s, 2147 sh v(C≡N); 1590, s,
v(C=N).
3-(2-cyanobenzyl)thiazolidin-2-ylidene-cyanamide (7)
white solid, yield: 0.496 g (85.7%), m.p.: 132–133 °C. 1H
NMR (400 MHz, CDCl3): δ (ppm) 2.30 (s, 3H, CH3), 3.33
(t, J = 7.6 Hz, 2H, NCH2), 3.67 (t, J = 7.6 Hz, 2H, SCH2),
4.62 (s, 2H, CH2), 7.14–7.28 (m, 4H, Ph). IR (KBr disc,
cm−1): 2918, w, ν(CH); 2180, s, 2143 sh v(C≡N); 1591,
s, v(C=N).
3-(4-cyanobenzyl)thiazolidin-2-ylidene-cyanamide (9)
white solid, yield: 0.514 g (87.3%), 138–139 °C. 1H NMR
(400 MHz, CDCl3): δ (ppm) 3.36 (t, J=7.5 Hz, 2H, NCH2),
1 3

Journal of Chemical Crystallography
Fig. 2 a Structure of 5, showing
the atom-labelling scheme of
one molecule in the asymmetric
unit. Displacement ellipsoids
are drawn at 30% probability
level and H atoms are shown as
small spheres of arbitrary radii.
The crystal structure of (b),
viewed along the c axis. Dashed
lines indicate C–H…N hydrogen
bonds
3.83–3.87 (t, J = 7.5 Hz, 2H, SCH2), 4.67 (s, 2H, CH2),
7.04–7.20 (m, 2H, Ph), 7.29–7.42 (m, 2H, Ph). IR (KBr
disc, cm−1): 2944, w, ν(CH); 2181, s, 2150 sh v(C≡N); 1590,
s, v(C=N).
3-(2-bromobenzyl)thiazolidin-2-ylidene-cyanamide (10)
white solid, yield: 0.511 g (84.3%), 122–123 °C. 1H NMR
(400 MHz, CDCl3): δ (ppm) 3.42 (t, J=7.5 Hz, 2H, NCH2),
3.94 (t, J=7.5 Hz, 2H, SCH2), 4.83 (s, 2H, CH2), 7.38–7.78
1 3

Journal of Chemical Crystallography
Table 2 Selected bond lengths (Å) and angles (°) for compound 4
with estimated standard deviations in parentheses
S(1)–C(1)
F(1)–C(11)
N(1)–C(3)
N(2)–C(1)
1.743(17)
1.358(2)
1.457(2)
S(1)–C(2)
N(1)–C(1)
N(1)–C(5)
N(2)–C(4)
1.798(2)
1.331(2)
1.458(2)
1.320(3)
1.307(2)
N(3)–C(4)
1.146(3)
92.35(9)
122.74(15)
111.77(16)
125.55(14)
175.0(2)
C(1)–S(1)–C(2)
C(1)–N(1)–C(5)
C(1)–N(2)–C(4)
N(2)–C(1)–S(1)
N(3)–C(4)–N(2)
C(1)–N(1)–C(3)
C(3)–N(1)–C(5)
N(2)–C(1)–N(1)
N(1)–C(1)–S(1)
116.55(16)
120.43(16)
121.74(16)
112.71(13)
Table 3 Selected bond lengths (Å) and angles (°) for compound 5
with estimated standard deviations in parentheses
S(1)–C(1)
F(1)–C(10)
N(1)–C(3)
N(2)–C(1)
1.739(2)
1.349(3)
1.461(2)
1.323(2)
S(1)–C(2)
N(1)–C(1)
N(1)–C(5)
N(2)–C(4)
1.808(2)
1.323(2)
1.463(3)
1.323(2)
N(3)–C(4)
1.148(3)
C(1)–S(1)–C(2)
C(1)–N(1)–C(5)
C(1)–N(2)–C(4)
N(2)–C(1)–S(1)
N(3)–C(4)–N(2)
91.14(10)
122.78(16)
116.78(17)
124.64(15)
174.8(2)
C(1)–N(1)–C(3)
C(3)–N(1)–C(5)
N(2)–C(1)–N(1)
N(1)–C(1)–S(1)
115.49(16)
121.11(16)
122.10(18)
113.26(14)
Table 4 Selected bond lengths (Å) and angles (°) for compound 6
with estimated standard deviations in parentheses
S(1)–C(1)
F(1)–C(9)
N(1)–C(3)
N(2)–C(1)
1.746(2)
1.362(3)
1.454(2)
1.315(3)
S(1)–C(2)
N(1)–C(1)
N(1)–C(5)
N(2)–C(4)
1.804(3)
1.324(2)
1.470(2)
1.329(3)
N(3)–C(4)
1.144(3)
C(1)–S(1)–C(2)
C(1)–N(1)–C(5)
C(1)–N(2)–C(4)
N(2)–C(1)–S(1)
N(3)–C(4)–N(2)
91.04(10)
122.86(17)
117.19(19)
124.85(16)
174.6(3)
C(1)–N(1)–C(3)
C(3)–N(1)–C(5)
N(2)–C(1)–N(1)
N(1)–C(1)–S(1)
115.72(17)
120.74(17)
122.08(19)
113.05(15)
Fig. 3 a Structure of 6, showing the atom-labelling scheme of one
molecule in the asymmetric unit. Displacement ellipsoids are drawn
at 30% probability level and H atoms are shown as small spheres of
arbitrary radii. The crystal structure of (b), viewed along the c axis.
Dashed lines indicate C–H…N and C–H…F hydrogen bonds
(t, J=7.6 Hz, 2H, NCH2), 3.76 (t, J =7.6 Hz, 2H, SCH2),
4.57(s, 2H, CH2), 7.19 (d, J = 8.4 Hz, 2H, Ph), 7.34–7.40
(m, 2H, Ph). IR (KBr disc, cm−1): 2950, w, ν(CH); 2181, s,
2140 sh v(C≡N); 1583, s, v(C=N).
3-benzylthiazolidin-2-ylidene-cyanamide (12) white
1
(m, 4H, Ph).IR (KBr disc, cm−1): 2940, w, ν(CH); 2182, s,
2149 sh v(C≡N); 1582, s, v(C=N).
solid, yield: 0.580 g (78.2%), 110–111 °C. H NMR
(400 MHz, CDCl3): δ (ppm) 3.28 (t, J=7.6 Hz, 2H, NCH2),
3.69 (t, J=7.6 Hz, 2H, SCH2), 4.54 (s, 2H, CH2), 7.18–7.44
(m, 5H, Ph). IR (KBr disc, cm−1): 2878, w, ν(CH); 2178, s,
2142, sh v(C≡N); 1583, s, v(C=N).
3-(4-chlorobenzyl)thiazolidin-2-ylidene-cyanamide (11)
white solid, yield: 0.548 g (80.2%), 112–113 °C. 1H NMR
(400 MHz, CDCl3): δ (ppm) 2.01–2.08 (s, 9H, (CH3)3), 3.34
1 3

Journal of Chemical Crystallography
Table 5 Hydrogen-bonding
system for compounds 4, 5
and 6 with estimated standard
deviations in parentheses
Compound
D–H⋅⋅⋅A
d(D–H) (Å)
d(H⋅⋅⋅A) (Å)
d(D⋅⋅⋅A) (Å)
∠(DHA) (deg)
4
5
C(5)–H(5B)⋅⋅⋅F(1)i
C(3)–H(3B)⋅⋅⋅N(3)ii
C(11)–H(11)⋅⋅⋅N(3)ii
C(3)–H(3A)⋅⋅⋅N(3)iii
C(5)–H(5B)⋅⋅⋅F(1)iv
0.97
0.97
0.93
0.97
0.97
2.56
2.66
2.69
2.58
2.48
3.277(2)
3.434(3)
3.546(3)
3.383(3)
3.440(3)
130.5
137.4
153.7
140.5
170.3
6
Symmetry codes: (i) –x+1, –y+1, –z+2; (ii)x, y, z–1; (iii)x, y, z‒1; (iv) –x, y+½, –z+3/2
3-(4-tert-butylbenzyl)thiazolidin-2-ylidene-cyanamide
the typical NCH2Ar protons appeared as singlet in the range
of 4.57–4.83 ppm. In the IR spectra of compounds 1–13,
the two peaks (a shoulder peak on the main peak) around
2190–2140 cm−1 could be assigned to the C≡N stretch-
ing vibration due to the possible syn-anti isomerism about
the C=N bond [18]. While the characteristic C=N stretch-
ing vibrations are shown as strong absorptions at around
1580 cm−1.
1
(13) white solid, yield: 0.533 (84.7%), 124–125 °C. H
NMR (400 MHz, CDCl3): δ (ppm) 3.29 (t, J = 7.6 Hz, 2H,
NCH2), 3.68 (t, J = 7.6 Hz, 2H, SCH2), 4.51 (s, 2H, CH2),
7.11–7.22 (m, 2H, Ph), 7.23–7.44 (m, 2H, Ph). IR (KBr
disc, cm−1): 2987, w, ν(CH); 2178, s, 2149 sh v(C≡N);
1585, s, v(C=N).
X‑Ray Crystallography
Molecular structures of compounds 4, 5 and 6 were fur-
ther confrmed by single crystal X-ray crystallography, as
shown in Figs. 1a, 2a, and 3a, respectively. Selected bond
lengths and angles are accordingly given in Tables 2, 3, 4.
The crystals of 5 and 6 are isomorphous. In the structures of
compounds 4‒6, the C(4)−N(3) bond lengths are 1.146(3),
1.148(3) and 1.144(3) Å, respectively, which indicate their
predominantly triple-bond character. The C(4)–N(2),
C(1)–N(2) and C(1)–N(1) bond lengths being of 1.320(3),
1.307(2), and 1.331(2) Å, respectively in 4, 1.323(2) Å in 5,
and according 1.329(3), 1.315(3), and 1.324(2) Å in 6, infer
their partial double bonds. Moreover, the N(3)–C(4)–N(2)
bond angles are 175.0(2)o for 4, 174.8(2)o for 5 and 174.6(3)o
for 6, indicatives of the typical N≡C–N=C(SCH2CH2)–N
group of thiazolidin-2-cyanamide compounds. The solid
states of compounds 4‒6 all adopt syn-isomerism about the
C=N bond, which are also observed in related thiazolidin-
2-cyanamide compounds [6, 8, 9, 19]. The dihedral angles
between the benzene and thiazolidine rings of compounds
4‒6 are 86.7(2)°, 75.5(2)°, and 77.1(2)°, respectively, which
are larger than those in benzoyl substituted related com-
pounds (ca. 63.0°) [8, 9]. The packing views of compounds
4–6 are shown in Figs. 1b, 2b, 3b, respectively. Crystal
packing in molecules 4–6 are governed by the weak inter-
molecular C–H⋅⋅⋅N and C–H⋅⋅⋅F hydrogen-bonding interac-
tions (see Table 5). The separations of C⋅⋅⋅N/F in molecules
4–6 are in the range of 3.277(2)‒3.546(3) Å, similar to the
C⋅⋅⋅N distance in (Z)-N-[3-(4-bromobenzoyl)-1,3-thiazoli-
din- 2-ylidene]cyanamide (3.281(5) Å) [9]. The bond angles
of C–H⋅⋅⋅N in molecules 2 and 3 are ranging from 137.4(1)°
to 153.7(2)°, while C–H⋅⋅⋅F bond angles are 130.5(1)° in
compound 4 and 170.3(2)° in compound 6. Moreover, H-pi
interactions (3.06 Å) of the phenyl groups exist in compound
4, and pi-pi interactions (3.79 Å) of the phenyl groups was
observed in compound 5.
A summary of crystallographic data and experimental details
for 3-(2-fuorobenzyl)thiazolidin-2-ylidene cyanamide (4),
3-(3-fuorobenzyl)- thiazolidin-2-ylidene cyanamide (5) and
3-(4-fuorobenzyl)thiazolidin-2-ylidene cyanamide (6) are
summarized in Table 1. Intensity data were collected on
a Bruker SMART APEX 2000 CCD difractometer using
graphite-monochromated Mo-Kα radiation (λ=0.71073 Å)
at 296(2) K. The collected frames were processed with the
software SAINT [12]. The data was corrected for absorption
using the program SADABS [13]. Structures were solved by
the direct methods and refned by full-matrix least-squares
on F2 using the SHELXTL software package [14, 15]. All
non-hydrogen atoms were refned anisotropically. The posi-
tions of all 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 fnal cycle of least-squares
refnement.
Results and Discussion
As shown in Scheme 2, the target compounds 1–13 were
conveniently synthesized by treatment of substituted benzyl
bromide compound with thiazolidin-2-ylidene-cyanamide in
acetonitrile at room temperature in good yields (80–90%). In
the 1H NMR spectra of compounds 1–13, the peaks in the
range of 6.96–7.78 ppm are attributed to the protons of the
aryl moiety. The triplet in the range of 3.20–3.50 ppm may
be attributed to the NCH2 proton and the signal in the range
of 3.65–3.98 ppm may be assigned to the proton of SCH2
with coupling constant being about 7.6 Hz, which agree well
to those in the known compounds [16, 17]. Chemical shift of
1 3

Journal of Chemical Crystallography
In summary, a new series of thiazolidin-2-cyanamide
derivatives containing various substituted benzyl moieties
were synthesized in good yields by an efcient method,
of which three compounds were further characterized by
single crystal X-ray crystallography, displaying the solid
states being of syn-isomerism characteristic of the C=N
bonds. There are weak C−H⋅⋅⋅N and C–H⋅⋅⋅F hydrogen
bonds in the crystal packing of compounds 4‒6 with
the separation of H⋅⋅⋅N/F being about 2.48‒2.69 Å (see
Figs. 1b, 2b and 3b).
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Acknowledgements This project was supported by the National Natu-
ral Science Foundation of China (Grant No. 21372007).
Publisher’s Note Springer Nature remains neutral with regard to
jurisdictional claims in published maps and institutional afliations.
Compliance with Ethical Standards
Conflict of interest The authors declare that they have no confict of
interest.
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