Synthesis and crystal structure analysis of thiourea-pendant pyridines

Article abstract of DOI:10.1007/s10870-008-9482-z

The crystal structures of pyridine containing thiourea moieties as substituents, (1) and (2), have been determined. The ortho-substituted pyridine (1) crystallized in monoclinic space group P2₁/c with a = 16.091(3) A, b=11.368(2) A, c = 7.4364(

Full text of DOI:10.1007/s10870-008-9482-z

J Chem Crystallogr (2009) 39:348–352
DOI 10.1007/s10870-008-9482-z
ORIGINAL PAPER
Synthesis and Crystal Structure Analysis of Thiourea-Pendant
Pyridines
Chomchai Suksai Æ Chaveng Pakawatchai Æ
Thawatchai Tuntulani
Received: 30 October 2007 / Accepted: 3 October 2008 / Published online: 21 October 2008
ꢀ Springer Science+Business Media, LLC 2008
Abstract The crystal structures of pyridine containing
thiourea moieties as substituents, (1) and (2), have been
determined. The ortho-substituted pyridine (1) crystallized
rodenticides [3, 4] and in connection with biomimetic
models [5]. Thiourea is well known as a good hydrogen
bond donor and has been used as anion recognition sites for
anion sensing using hydrogen bonding interactions [6, 7].
Furthermore, thiourea functionalities can form diverse
hydrogen-bonded networks, making them a powerful
building block for crystal engineering [8, 9].
˚
in monoclinic space group P21/c with a = 16.091(3) A,
˚
˚
b = 11.368(2) A, c = 7.4364(14) A, b = 100.489(4)8,
3
V = 1337.5(4) A , z = 4. In this structure an intramolecular
˚
N–HÁÁÁN hydrogen bond forms a pseudo-seven-membered
ring. The meta-substituted pyridine (2) crystallized in
˚
monoclinic space group P21/c with a = 14.5408(15) A,
In this work we present the synthesis and structural X-
ray analysis of two thiourea-pendant pyridines. The influ-
ence of the position of the substituents on the pyridine ring
regarding intra- and intermolecular hydrogen bonding
interactions between molecules in crystals has been
discussed.
˚
˚
b = 8.8508(9) A, c = 10.7959(11) A, b = 106.435(2)8,
3
V = 1332.6(2) A , z = 4. Crystal packing revealed that
˚
compounds (1) and (2) can form dimeric structures via
intermolecular H-bonding using N–HÁÁÁS and N–HÁÁÁN
interactions, respectively.
Keywords Pseudo-seven-membered ring Á
Experimental
Heterocyclic thiourea
General
Introduction
All reagents were of reagent grade and were used without
1
further purification unless stated otherwise. H-NMR, 13C-
Thioureas are of importance in medicinal chemistry due to
their biological activity [1] as anti-bacteria and anti-
microbial infection [2], as fungicides, herbicides, and
NMR spectra were record in DMSO-d6 on a BRUKER
AVANCE 400 NMR spectrometer. Elemental analyses for
C, H and N were performed on a Perkin-Elmer 2400 CHN
elemental analyzer.
C. Suksai (&)
Department of Chemistry, Faculty of Science, Burapha
University, Chonburi 20131, Thailand
e-mail: jomjai@buu.ac.th
Synthesis
Scheme 1
C. Pakawatchai
Department of Chemistry, Faculty of Science, Prince of Songkla
University, Songkhla 90112, Thailand
1-(4-Nitrophenyl)-2-pyridin-2-ylmethylthiourea (1)
To a well stirred solution of 2-picolylamine (0.16 mL,
1.64 mmole) in dry CH2Cl2 (10 mL) was slowly added a
solution of 4-nitrophenylisothiocyanate (0.44 g, 2.46 mmole)
T. Tuntulani
Department of Chemistry, Faculty of Science, Chulalongkorn
University, Bangkok 10330, Thailand
123

J Chem Crystallogr (2009) 39:348–352
349
NO2
NO2
SHELXL-97 [10] on WinGX package [11]. All non-
hydrogen atoms were refined with anisotropic thermal
parameters in the latter stage of refinement. All hydrogen
atoms (except H14 and H15) placed in geometrically ide-
alized positions and refined as riding atoms. Packing
diagrams were produced using Mercury [12]. The detailed
crystallographic data and structure refinement parameters
of (1) and (2) are summarized in Table 1.
S
CH2Cl2
NO2
N
N
NH2
+
H
H
N
N
SCN
(1)
S
CH2Cl2
NO2
N
N
NH2
+
H
H
N
N
SCN
(2)
Scheme 1 Preparation of 1-(4-Nitrophenyl)-2-pyridin-2-ylmethylthiou-
rea (1) and 1-(4-Nitrophenyl)-3-pyridin-3-ylmethylthiourea (2)
Table 1 Crystallographic data and final refinement of (1) and (2)
in dry CH2Cl2 (10 mL). The mixture was stirred for 3 days
under N2 leading to formation of a precipitate. The pale yel-
low product was isolated by filtration, washed with
dichloromethane and dried in vacuo (0.31 g, 66%). m.p.:
159–160ꢁC. 1H NMR (400 MHz, DMSO-d6) d;10.537 (s, 1H,
–NH–), 8.790 (s, 1H, –NH–), 8.570 (s, 1H, ArH), 8.202 (d,
J = 7.2 Hz, 2H, ArH), 7.940(d, J = 7.6 Hz, 2H, ArH), 7.805
(m, 1H, ArH), 7.410 (m, 1H, ArH), 7.318 (m, 1H, ArH), 4.860
(s, 2H, –CH2–). 13C NMR (100 MHz, DMSO-d6) d; 180.76,
157.22, 149.30, 146.83, 142.41, 137.30, 124.97, 122.89,
122.15, 120.99, 49.29. Anal. Calcd. for C13H12N4O2S C,
54.15; H, 4.20; N, 19.43. Found: C, 54.17; H, 4.18; N, 19.48.
(1)
(2)
CCDC Number
Formula
665445
665446
C13H12N4O2S
288.33
C13H12N4O2S
288.33
Formula weight
Temperature
Crystal system
Space group
293(2) K
Monoclinic
P21/c
293(2) K
Monoclinic
P21/c
˚
a (A)
16.091(3)
11.368(2)
7.4364(14)
100.489(4)
Colourless
14.5408(15)
8.8508(9)
10.7959(11)
106.435(2)
Colourless
˚
b (A)
˚
c (A)
b (8)
Color
1-(4-Nitrophenyl)-3-pyridin-3-ylmethylthiourea (2)
Size (mm)
0.222 9 0.18 9 0.088 0.254 9 0.13 9 0.111
3
˚
Volume (A )
1337.5(4)
4
1332.6(2)
4
To a well stirred solution of 3-picolylamine (0.16 mL,
1.64 mmol) in dry CH2Cl2 (10 mL) was slowly added a
solution of 4-nitrophenylisothiocyanate (0.44 g, 2.46 mmol)
in dry CH2Cl2 (10 mL). The mixture was stirred for 3 days
under N2 leading to formation of a precipitate. The pale
yellow product was isolated by filtration, washed with
dichloromethane and dried in vacuo (0.33 g, 70%). m.p.:
Z
qcalc (g cm-3
)
1.432
0.249
1.437
0.250
Absorption
coefficient
(mm-1
)
T
min, Tmax
0.962, 0.973
600
0.947, 0.978
600
F(000)
1
Theta range for
data collection
1.29 to 28.068
1.46 to 28.058
184–185ꢁC. H NMR (400 MHz, DMSO-d6) d; 10.356 (s,
1H, –NH–), 8.790 (s, 1H, –NH–), 8.674 (s, 1H, ArH), 8.597
(m, 1H, ArH), 8.188, (d, J = 8.4 Hz, 2H, ArH), 7.859 (d,
J = 8.4 Hz, 2H, ArH), 7.786 (d, J = 7.2 Hz, 1H, ArH),
7.380 (m, 1H, ArH), 3.488 (s, 2H, –CH2–).13C NMR
(100 MHz, DMSO-d6) d; 181.09, 149.40, 148.67, 146.67,
142.49, 135.89, 134.46, 124.93, 123.94, 121.29, 45.22. Anal.
Calcd. for C13H12N4O2S C, 54.15; H, 4.20; N, 19.43. Found:
C, 54.10; H, 4.24; N, 19.45.
Index ranges
-21 B h B 21
-14 B k B 15
-9 B l B 9
-18 B h B 19
-11 B k B 11
-14 B l B 14
15,544
Reflections collected 15,600
Independent
reflections
3,212
[R(int) = 0.0335]
3,237
[R(int) = 0.0394]
Absorption
correction
None
None
Data/restraints/
parameters
3,212/0/189
1.095
3,237/0/189
1.129
Crystal Structure Determination of (1) and (2)
Goodness-of-fit
on F2
X-ray quality crystals were obtained by slow evaporation
of acetonitrile solutions of (1) and (2). Crystallographic
data was collected on a BRUKER APEX CCD diffrac-
trometer (graphite-monochromated Mo-Ka radiation with
k = 0.71073 A). The structures were solved by direct
methods using the program SHELXS-97 and refined by
full-matrix least squares techniques against F2 using the
Final R indices
[I [ 2r(I)]
R1 = 0.0481
R1 = 0.0523
wR2 = 0.1118
wR2 = 0.1142
R1 = 0.0689
R indices (all data) R1 = 0.0618
wR2 = 0.118/8
wR2 = 0.1216
0.286 and -0.157
˚
Largest diff. peak
˚
and hole (e. A
0.232 and -0.231
-3
)
123

350
J Chem Crystallogr (2009) 39:348–352
Results and Discussion
Table 2 continued
C(2)–C(1)–N(1)
C(3)–C(2)–C(1)
C(2)–C(3)–C(4)
C(3)–C(4)–C(5)
C(3)–C(4)–N(2)
C(5)–C(4)–N(2)
C(6)–C(5)–C(4)
C(1)–C(6)–C(5)
N(3)–C(7)–N(2)
N(3)–C(7)–S(1)
N(2)–C(7)–S(1)
N(3)–C(8)–C(9)
119.2(2)
C(13)–C(9)–C(8)
C(11)–C(10)–C(9)
C(12)–C(11)–C(10)
N(4)–C(12)–C(11)
N(4)–C(13)–C(9)
O(1)–N(1)–O(2)
O(1)–N(1)–C(1)
O(2)–N(1)–C(1)
C(7)–N(2)–C(4)
C(7)–N(3)–C(8)
C(13)–N(4)–C(12)
120.39(17)
119.89(18)
118.97(19)
122.8(2)
The reactions of 2- and 3-picolylamine with phenylisothi-
ocyanate gave the corresponding heterocyclic thiourea
derivatives (1) and (2), respectively. Bond distances and
angles of compounds (1) and (2) are given in Table 2.
118.8(2)
120.91(19)
119.19(18)
117.21(17)
123.48(18)
119.68(19)
120.03(19)
112.55(16)
122.46(14)
124.93(14)
112.67(16)
124.79(19)
123.1(2)
˚
Table 2 Selected bond distances (A) and angles (ꢁ) of (1) and (2)
118.2(2)
Bond distances
118.7(2)
(1)
129.43(16)
125.52(16)
117.13(18)
C(1)–C(2)
1.374(2)
1.382(2)
1.461(2)
1.378(2)
1.411(2)
1.375(2)
1.336(2)
1.352(2)
1.6917(17)
1.463(2)
C(8)–C(9)
1.508(3)
1.339(2)
1.380(3)
1.381(3)
1.367(3)
1.371(3)
1.335(2)
1.215(2)
1.216(2)
C(1)–C(6)
C(9)–N(4)
C(1)–N(1)
C(9)–C(10)
C(10)–C(11)
C(11)–C(12)
C(12)–C(13)
C(13)–N(4)
N(1)–O(2)
N(1)–O(1)
C(2)–C(3)
C(4)–N(2)
C(5)–C(6)
˚
Table 3 Hydrogen bonds distances (A) and angles (ꢁ) for (1) and (2)
C(7)–N(3)
D–HÁÁÁA
D–H
HÁÁÁA
DÁÁÁA
D–HÁÁÁA
C(7)–N(2)
C(7)–S(1)
(1)
C(8)–N(3)
N(2)–H(14)…N(4)
N(3)–H(15)…S(1)i
(2)
N(2)–H(14)…N(4)ii 0.89(2) 2.02(2) 2.902(2)
N(3)–H(15)…N(4)ii 0.80(2) 2.69(2) 3.309(3)
N(3)–H(15)…S(1)iii 0.80(2) 2.84(2) 3.4429(17)
0.85(2) 1.98(2) 2.793(2)
162.2(19)
(2)
0.80(2) 2.58(2) 3.3459(17) 160.3(19)
C(1)–C(6)
1.370(3)
1.379(3)
1.458(3)
1.372(3)
1.389(3)
1.396(3)
1.401(2)
1.374(3)
1.340(2)
1.360(2)
1.6758(18)
C(8)–N(3)
C(8)–C(9)
1.452(2)
1.507(3)
1.382(3)
1.383(3)
1.374(3)
1.374(3)
1.333(3)
1.330(3)
1.218(3)
1.222(3)
C(1)–C(2)
171(2)
135(2)
134(2)
C(1)–N(1)
C(9)–C(10)
C(9)–C(13)
C(10)–C(11)
C(11)–C(12)
C(12)–N(4)
C(13)–N(4)
N(1)–O(1)
N(1)–O(2)
C(2)–C(3)
C(3)–C(4)
Symmetry transformations used to generate equivalent atoms: (i) -x,
-y, -z, (ii) -x, -y ? 2, -z, (iii) x, -y ? 5/2, z-1/2
C(4)–C(5)
C(4)–N(2)
C(5)–C(6)
C(7)–N(3)
C(7)–N(2)
C(7)–S(1)
Bond angles
(1)
C(2)–C(1)–C(6)
C(2)–C(1)–N(1)
C(6)–C(1)–N(1)
C(1)–C(2)–C(3)
C(2)–C(3)–C(4)
C(3)–C(4)–C(5)
C(3)–C(4)–N(2)
C(5)–C(4)–N(2)
C(6)–C(5)–C(4)
C(5)–C(6)–C(1)
N(3)–C(7)–N(2)
N(3)–C(7)–S(1)
N(2)–C(7)–S(1)
N(3)–C(8)–C(9)
(2)
122.22(15)
119.42(15)
118.36(16)
118.50(15)
120.32(16)
120.22(15)
117.67(15)
121.95(14)
119.75(15)
118.98(16)
115.50(15)
120.54(12)
123.89(13)
115.27(16)
N(4)–C(9)–C(10)
N(4)–C(9)–C(8)
C(10)–C(9)–C(8)
C(9)–C(10)–C(11)
C(12)–C(11)–C(10)
C(11)–C(12)–C(13)
N(4)–C(13)–C(12)
O(2)–N(1)–O(1)
O(2)–N(1)–C(1)
O(1)–N(1)–C(1)
C(7)–N(2)–C(4)
C(7)–N(3)–C(8)
C(13)–N(4)–C(9)
121.70(18)
115.30(16)
122.99(17)
118.81(19)
119.60(19)
118.3(2)
123.10(19)
123.01(18)
118.26(17)
118.73(18)
127.21(15)
127.16(15)
118.44(16)
Fig. 1 Molecular structure of (1). Thermal ellipsoids shown at 50%
possibility
Hydrogen bond distances and angles of those two com-
pounds are presented in Table 3. Compound (1) crystallized
in the monoclinic space group P21/c. A molecular diagram
of the H-bonded dimeric structure is shown in Fig. 2. It
should be noted that the compound (1) possesses an intra-
molecular N–HÁÁÁN hydrogen bond (H(14)ÁÁÁN(4) =
C(6)–C(1)–C(2)
C(6)–C(1)–N(1)
121.38(19)
119.4(2)
C(10)–C(9)–C(13)
C(10)–C(9)–C(8)
116.44(18)
123.17(17)
˚
1.98(2) A and N(2)–H(14)ÁÁÁN(4) = 162.2(19)ꢁ) forming a
pseudo-seven-membered ring, thus locking the molecular
123

J Chem Crystallogr (2009) 39:348–352
351
conformation and eliminating conformational flexibility
(Fig. 1). The crystal structure of (1) also shows intermo-
lecular interactions of the N–HÁÁÁS bonds (H(15)ÁÁÁS(1)i =
i
˚
2.58(2) A and N(3)–H(15)ÁÁÁS(1) = 160.3(19)ꢁ) generating
a dimeric structure along the crystallographic ‘a’-axis
(Fig. 2).
Compound (2) also crystallized in monoclinic space
group P21/c, Fig. 3. However, there is no intramolecular
hydrogen bonding in the structure. The structure of (2) had
a different intermolecular hydrogen bonding pattern when
compared to (1). There are pairs of intramolecular hydro-
gen bond between the nitrogen pyridine and NH thioureas
(H(14)ÁÁÁN(4) = 2.02(2) A and N(2)–H(14)ÁÁÁN(4)ii =
Fig. 4 The N–HÁÁÁN intramolecular hydrogen bonding in the dimeric
structure of (2)
ii
˚
ii
˚
171(2)8 and H(15)ÁÁÁN(4) = 2.69 A and N(3)–H(15)ÁÁÁ
N(4)ii = 135(2)8), Fig. 4.
The packing is not only stabilized by hydrogen bonding,
175.51(18)ꢁ for (1) and (2), respectively. This is due to the
formation of a pseudo-seven-membered ring in compound
(1).
but also by p–p packing interactions in the distance of
˚
˚
3.683 A (PhenylÁÁÁPhenyl) and 3.718 A (PyridineÁÁÁPyri-
dine) responsible for the crystal packing of (1). It should be
mentioned that the relatively long NÁÁÁS distances
encountered for both compounds are facilitated by reso-
nance lengthening of C=S [13] and are similar to those of
previously determined thiourea dimers [14–16]. Moreover,
the torsion angles of N2–C7–N3–C8 are -11.8(3)ꢁ and
From the structural features described above it is clear
that the intramolecular hydrogen bonding has been found
in the ortho-pyridine substituted thiourea derivatives. In
addition, the supramolecular aggregation in both structures
are due to N–HÁÁÁN, N–HÁÁÁS and pÁÁÁp intermolecular
interactions.
Supplementary Material
Supplementary crystal data are available from the CCDC,
12 Union Road, Cambridge, CB2 1EZ, UK (fax: ?44-
1223-336033; e-mail: deposit@ccdc.cam.ac.uk or www:
http://www.ccdc.cam.ac.uk) on request, quoting the depo-
sition numbers: CCDC 665445 and 665446 for compounds
(1) and (2), respectively.
Acknowledgements Financial support from the Thailand Research
Fund (MRG5080149 and RTA5080006) and the Center of Excellence
for Innovation in Chemistry (PERCH-CIC), Commission on Higher
Education, Ministry of Education are gratefully acknowledged.
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