Structural studies of N-2-(3-picolyl)- and N-2-(4-picolyl)-N′ -tolylthioureas

Article abstract of DOI:10.1023/A:1021136508168

Reactions of 2-aminopicolines with 2- and 4-tolyl isothiocyanates yielded N-2-(4-picolyl)-N′-4-tolylthiourea, 1, N-2-(3-picolyl)-N′ -4-tolylthiourea, 2, and N-2-(4-picolyl)-N′-2-tolylthiourea, 3. Compound 1 is monoclinic, of space group P2₁/c with a = 7.456(1) A, b = 13.135(3) A, c = 13.959(3) A, β = 104.99(3)°, and V = 1320.5(5) A³ with Z = 4, for d_calc = 1.294 g/cm ³. Compound 2 is triclinic, of space group P1 with a = 6.877(3) A, b = 7.590(5) A, c = 13.213(9) A, α = 78.38(2)°, β = 77.96(4)°, γ = 86.36(4)°, and V = 660.5(7) A ³ with Z = 2, for d_calc = 1.294 g/cm³. Compound 3 is monoclinic, of space group P2₁/c with a = 12.604(2) A, b = 15.592(3) A, c = 6.875(2) A, β = 91.05(2)°, and V = 1350.9(2) A³ with Z = 4, for d_calc = 1.265 g/cm³. The three thioureas are found in both solid state and solution in a conformation resulting from intramolecular N-H ... N hydrogen bonding. Compounds 1 and 3 present an intermolecular hydrogen bond involving the thione sulfur and the NH hydrogen, which is not present in 2 owing to the steric hindrance of the methyl group in the phenyl ring. The geometry of the molecule is affected by the position of the methyl groups on the pyridine and aryl rings.

Full text of DOI:10.1023/A:1021136508168

C
Journal of Chemical Crystallography, Vol. 32, No. 11, November 2002 ( 2002)
Structural studies of N-2-(3-picolyl)- and
N-2-(4-picolyl)-N0-tolylthioureas
Jesu´s Valde´s-Mart´ınez,(1) Simo´n Herna´ndez-Ortega,(1) Anne K. Hermetet,(2)
Lily J. Ackerman,(2) Carmina A. Presto,(2) John K. Swearingen,(2) Diantha R. Kelman,(3)
Karen I. Goldberg,(3) Werner Kaminsky,(3) and Douglas X. West(3)
Received August 10, 2001
Reactions of 2-aminopicolines with 2- and 4-tolyl isothiocyanates yielded N-2-(4-picolyl)-
N0-4-tolylthiourea, 1, N-2-(3-picolyl)-N0-4-tolylthiourea, 2, and N-2-(4-picolyl)-N0-2-
˚
tolylthiourea, 3. Compound 1 is monoclinic, of space group P21/c with a = 7.456(1) A,
3
˚
˚
˚
b = 13.135(3) A, c = 13.959(3) A, = 104.99(3) , and V = 1320.5(5) A with Z = 4,
3
¯
for dcalc = 1.294 g/cm . Compound 2 is triclinic, of space group P1 with a = 6.877(3)
˚
˚
˚
A, b = 7.590(5) A, c = 13.213(9) A, = 78.38(2) , = 77.96(4) , = 86.36(4) , and
V = 660.5(7) A with Z = 2, for dcalc = 1.294 g/cm3. Compound 3 is monoclinic, of space
3
˚
˚
˚
˚
group P21/c with a = 12.604(2) A, b = 15.592(3) A, c = 6.875(2) A, = 91.05(2) , and
V = 1350.9(2) A with Z = 4, for dcalc = 1.265 g/cm3. The three thioureas are found in
3
˚
both solid state and solution in a conformation resulting from intramolecular N H
N
hydrogen bonding. Compounds 1 and 3 present an intermolecular hydrogen bond involv-
ing the thione sulfur and the NH hydrogen, which is not present in 2 owing to the steric
hindrance of the methyl group in the phenyl ring. The geometry of the molecule is affected
by the position of the methyl groups on the pyridine and aryl rings.
KEY WORDS: Thiourea; pyridine; hydrogen bonding.
N0-arylthioureas3–6 show the presence of this in-
Introduction
tramolecular hydrogen bond. Also present in the
1
The H NMR spectra of 2-pyridyl thioureas
solid state is an intermolecular NH hydrogen bond
to a sulfur of a neighboring molecule (Fig. 1).
In order to study the influence of substituents
on the aryl and pyridyl rings on the geome-
try of the molecules and on the intra- and in-
termolecular hydrogen bonds, in this paper we
indicate the presence of an intramolecular hydro-
gen bond between N0H and the pyridyl nitrogen
in solution.1 The solid-state structures of 2-
pyridyl thiourea2 and substituted N-(2-pyridyl)-
1
(1) Instituto de Qu´ımica, Universidad Nacional Auto´noma de Me´xico
Circuito Exterior, Ciudad Universitaria, Coyoaca´n 04510, Cd.
Me´xico DF, Me´xico.
(2) Department of Chemistry, Illinois State University, Normal,
Illinois 61790-4160.
(3) Department of Chemistry, 351700, University of Washington,
Seattle, Washington 98195-1700.
To whom correspondence should be addressed. E-mail: jvaldes@
servidor.unam.mx.
present the H NMR spectra and crystal struc-
tures of N-2-(4-picolyl)-N0-4-tolylthiourea, 1, N-
2-(3-picolyl)-N0-4-tolylthiourea, 2, and N-2-(4-
picolyl)-N0-2-tolylthiourea, 3. In 1 the methyl
groups are away from the thiourea moieties, but in
2 and 3 there are methyl groups alpha to the carbon
bonded to the nitrogen on the pyridine ring (2) or
431
C
1074-1542/02/1100-0431/0 2002 Plenum Publishing Corporation

432
Valde´s-Mart´ınez et al.
follows: 3, 189–191 C; 2, 116–118 C; and 1,
184–186 C. The 1H NMR spectra were recorded
in CDCl3 with a Bruker 300-MHz spectrometer
and the enthalpies of fusion were obtained with
approximately 3-mg samples at a heating rate
of 10 C/min using a Perkin-Elmer differential
scanning calorimeter, DSC7.
Crystals were grown by slow evaporation
of acetone–anhydrous ethanolic mixtures (1:1
by volume) at room temperature. The colorless
thiourea crystals were mounted in random ori-
entation on a glass fiber, and the structures were
solved by direct methods and missing atoms were
found by difference Fourier synthesis. The non-
hydrogen atoms were refined with anisotropic
temperature factors. Hydrogens attached to nitro-
gens and ring carbons were refined isotropically,
and the methyl hydrogens were allowed to ride
on their carbons and assigned a fixed isotropic
Fig. 1. Intra- and intermolecular hydrogen bonding found in
N-2-picolyl-N0-tolylthioureas.
the phenyl ring (3), and these may have a steric in-
fluence on the geometry of the molecule and, in 2
on the intermolecular hydrogen bonding (Fig. 2).
2
˚
temperature factor, U = 0.05 A . For 1, scatter-
Experimental
ing factors were taken from International Tables
for X-ray Crystallography (1974, Vol. IV)8 and
calculations were done with the SHELXTL PCTM
program package.9 Scattering factors for 3 and 2
are from Wassmaier and Kirfel,10 and calculations
were done by MaXus, version 2.0.11 Table 1 sum-
marizes the crystal data, collection information,
and refinement data for these thioureas.
2-Amino-3-picoline
and
2-amino-4-
picoline, as well as 2-tolyl- and 4-tolyl isoth-
iocyanate, were purchased from Aldrich and
used as received. 2-Aminopicoline was mixed
with a tolyl isothiocyanate in a 1:1 molar ratio
(e.g., 2 mmol) in 30 mL of 95% ethanol, and
the mixture was stirred with gentle warming
for a minimum of 1 h. On cooling and slowly
evaporating the reactant mixture (35 C), the
thioureas crystallized from solution. The crystals
were filtered, washed with cold 2-propanol, and
dried. The yields were approx. 70% for each
of the thioureas and the melting points are as
Results
The thermal ellipsoid plots of 1–3 are shown
in Fig. 3. Selected bond distances and angles are in
Table 2 and hydrogen-bonding geometries are in
Fig. 2. Drawings of (a) 1, (b) 2, and (c) 3.

N-2-Picolyl-N0-tolylthioureas
433
Table 1. Crystallographic Data for 1, 2, and 3
Crystal data
1
2
3
CCDC no.
163123
163124
163125
Crystal color, habit
Empirical formula
Formula weight
Temperature, K
Crystal size, mm
Crystal system
Space group
Colorless, prism
C14H15N3S
257.35
Colorless, prism
C14H15N3S
257.35
Colorless, prism
C14H15N3S
257.35
293(2)
130(2)
293(2)
0.32 0.28 0.20
Monoclinic
P21/c
0.26 0.17 0.05
Triclinic
0.32 0.20 0.20
Monoclinic
P21/c
¯
P1 (No. 2)
˚
a, A
12.604(2)
15.592(3)
6.875(2)
90
91.05(2)
90
1350.9(6)
4
1.265
6.877(3)
7.590(5)
13.213(9)
78.38(2)
77.96(4)
86.36(4)
660.5(7)
2
7.456(1)
13.135(3)
13.959(3)
90
104.99(3)
90
1320.5(5)
4
1.294
˚
b, A
˚
c, A
, deg
, deg
, deg
Volume, A
3
˚
Z
Density (calcd.), Mg/m3
Absorption coefficients, mm
Diffractometer
range for data collection, deg
Reflections measured
1.294
0.230
1
0.225
2.047
Nonius MACH3
1.61–27.39
3249
Nonius Kappa CCD Siemens P4
5.16–21.95
2289
4.7–55.04
1701
Independent reflections (Rint
Observed reflections
Data/restraints/parameters
Extinction coefficient
Goodness of fit
)
2985 (0.0205)
1437 [I > 2.0 (I)] 628 [I > 2.0 (I)]
2985/0/202
0.00605
1.136
1416 (0.1413)
1550 (0.0433)
1295 [F > 3.0 (F)]
1550/0/170
0.0017(5)
1416/0/201
0
0.703
1.45
R, wR
R, wR (all data)
0.0589, 0.0963
0.1436, 0.1448
0.0530, 0.0950
0.1587, 0.1337
0.0462, 0.1306
0.0553, 0.1367
Table 3. The conformation of the thioureas is such
that the C2 of the pyridine ring and the S atom are
anti with respect to the N2 C7, and C8 from the
phenyl ring and the S atom are syn with respect
to C7 N3. An intramolecular hydrogen bond be-
tween N3 H and N1 is present in 1–3, with a
N3 N1 distance equal to 2.630(3), 2.631(8), and
C H
Fig. 4.
S interactions are present, as shown in
The DSC plots of these thioureas show a
sharp peak due to melting, followed immediately
by a broader peak representing decomposition.
The enthalpies of fusion are as follows: 1, 44.6
kJ/mol; 2, 22.5 kJ/mol; and 3, 53.7 kJ/mol.
˚
2.646(4) A, respectively (Fig. 4). The angle be-
tween the pyridine ring and the thiourea moiety
(N2 C7 S1 N3) in 1–3 is 4.5(1), 8.1(2), and
9.7(1) , respectively, and the angle between the
phenyl ring and the thiourea moiety is 21.7(1),
8.0(2), and 73.4(1) respectively.
Discussion
Compounds 1–3 were synthesized in good
yields from the reaction between the appropri-
ate 2-aminopicoline and tolyl isothiocyanate. The
1H NMR spectra of 1–3 show that N3H is
downfield from the rest of the signals, 13.477,
13.777, and 13.571 ppm, respectively, indicat-
ing its involvement in intramolecular hydrogen
bond.
The molecules in
1
and
3
form
self-complimentary
NH
= 3.438(3)
S
hydrogen
˚
x, y, z)
bonds, N2 S1(1
A
and
N2 S1(1
= 3.437(3) A, respectively. In
x, y,2 z)
˚
2 instead of this N H
S hydrogen bonds two

434
Valde´s-Mart´ınez et al.
Fig. 3. Thermal ellipsoid diagram showing intramolecular hydrogen
bonding for (a) 1, (b) 2, and (c) 3, with atom numbering scheme and
displacement ellipsoids at 30% probability level.

N-2-Picolyl-N0-tolylthioureas
435
˚
Table 2. Selected Bond Distances (A) and Angles (Deg) for 1, 2,
portant influence on the intermolecular hydrogen
bonding, as will be seeing.
and 3
Thioureas tend to form intermolecular
1
2
3
N H
S hydrogen bonds. In cyclic thioureas
S hydrogen bonds
Bond distances
S1 C7
the intermolecular N H
produce tapes and force molecules on one side
of the tape to reside in a plane that is parallel
1.683(3)
1.328(4)
1.349(4)
1.411(4)
1.369(4)
1.327(4)
1.431(4)
1.666(7)
1.319(7)
1.351(7)
1.400(7)
1.410(7)
1.334(7)
1.410(7)
1.680(3)
1.321(4)
1.338(4)
1.404(4)
1.368(4)
1.323(4)
1.417(4)
N1 C2
N1 C6
N2 C2
N2 C7
N3 C7
N3 C8
˚
to, but separated ( 1 A) from, the plane occu-
pied by the molecules on the other side of the
tape.13 In the crystal structure of 1, 2, and 3,
there are two molecules in parallel planes that
Bond angles
may form self-complimentary N H
actions, but in each one the step between the
S inter-
C2 N2 C7
C7 N3 C8
N1 C2 N2
N2 C2 C3
S1 C7 N2
S1 C7 N3
N2 C7 N3
N3 C8 C9
N3 C8 C13
129.7(3)
126.0(3)
118.5(3)
117.9(3)
118.9(3)
124.2(3)
116.8(3)
121.7(4)
117.0(4)
130.3(5)
133.1(6)
118.5(5)
117.3(6)
117.1(5)
128.8(5)
114.2(5)
125.9(6)
115.1(6)
130.9(3)
131.8(3)
118.1(3)
118.3(3)
117.3(2)
127.1(2)
115.6(3)
116.8(3)
125.2(3)
molecules is very different. In 1 the height of
˚
the step is 1.40 A, higher than that observed
in cyclic thioureas, but distances and angles are
within the accepted values for N H
gen bonds. In 2, owing to the steric hindrance of
S hydro-
the methyl group in the phenyl ring, the height
˚
of the step is 2.50 A, and no N H
formed; instead C H S hydrogen bonds are
present. In 3 the height of the step is only 0.35 A,
and the self-complimentary N H S as well as
C(3) H(3) S(1) are present, as shown in Fig. 5.
S bond is
The three thioureas reported here, like
other 2-pyridyl thioureas,2–6 are found in a con-
formation resulting from intramolecular hydro-
gen bonding. This result is in agreement with
Etter’s hydrogen-bond rules, which indicate that
intramolecular hydrogen-bonded six-membered
rings are favored as compared to rings with inter-
molecular hydrogen bond12. Because of this hy-
drogen bond, the angle between the pyridine ring
and the thiourea moiety mean planes is less than
15 .2–4,6,7 This hydrogen bond locks the pyridine
ring and it cannot rotate freely: this has an im-
˚
The present 2-pyridyl thioureas have simi-
lar bond distances and angles, with the most no-
table difference being the longer N2 C7 bond
distance for 2 and the shorter C7 N3 C8 and
S1 C7 N3 bond angles for 3. The previously re-
ported N-2-(3-picolyl)- and N-2-(4-picolyl)-N0-
2-phenylthioureas have bond distances and an-
gles similar to those found here.6 There is a
Table 3. Hydrogen Bond Parameters for 1, 2, and 3
˚
˚
˚
D
H
A
D
H (A)
H
A (A)
D
A (A)
D
H
A (deg)
Symmetry code
1
N3 H3A
N2 H2
N1
S1
0.81(3)
0.79(3)
1.95(3)
2.72(3)
2.630(4)
3.437(3)
141(3)
152(3)
1
x, y,
z
z
2
N3 H3N
C13 H13
C15 H15C
N1
S1
S1
0.8801
0.9506
0.9798
1.8570
2.8566
2.7921
2.631(7)
3.687(8)
3.752(7)
145.70
146.52
166.49
x, 1 + y, z
x, 2 y,
3
N3 H3A
N2 H2A
C(3) H(3)
N1
S1
S(1)
0.90(5)
0.88(3)
0.95(3)
1.88(4)
2.57(4)
2.84(3)
2.646(4)
3.437(3)
3.674(4)
142(4)
167(3)
147(2)
1
1
x, y, 2
x, y, 2
z
z

436
Valde´s-Mart´ınez et al.
Fig. 4. Intermolecular hydrogen bonding for (a) 1 and (b) 3.

N-2-Picolyl-N0-tolylthioureas
437
Fig. 5. Packing diagrams for (a) 1, (b) 2, and (c) 3.

438
Valde´s-Mart´ınez et al.
considerable difference in the angle between the
phenyl ring and the thiourea moiety in 3 as com-
pared to that in 1 and 2, 3 being the most dis-
torted molecule. Among the 2-pyridyl thioureas
with methyl groups on one or both rings,2–4,6,7
2 is the least distorted and N-(2-pyridyl)-N0-3-
tolylthiourea is the most distorted.6 In 3 and N-
(2-pyridyl)-N0-3-tolylthiourea the distortion may
be due to the steric hindrance of the methyl group
in the phenyl ring. The tilt of the phenyl ring in 3
affects the way the molecules pack in the crystal,
as shown in Fig. 5.
Acknowledgments
We acknowledge the Camille and Henry Dreyfus
Foundation, the Donors of the Petroleum Research
Fund, administered by the American Chemical Soci-
ety, the National Science Foundation, the Universidad
Nacional Auto´noma de Me´xico for the partial support
of this research.
References
1. Kascheres, A.; Ueno, M. J. Heterocycl. Chem. 1991, 28, 2057.
2. West, D.X.; Hermetet, A.K.; Ackerman, L.J.; Valde´s-Mart´ınez,
J.; Herna´ndez-Ortega, S. Acta Crystallogr., Sect. C 1999, 55,
811.
Conclusions
3. Valde´s-Mart´ınez, J.; Herna´ndez-Ortega, S.; West, D.X.;
Ackerman, L.J.; Swearingen, J.K.; Hermetet, A.K. J. Mol.
Struct. 1999, 478, 219.
4. West, D.X.; Swearingen, J.K.; Hermetet, A.K.; Ackerman, L.J.;
Presto, C. J. Mol. Struct. 2000, 522, 27.
5. Sudbeck, E.A.; Jennissen, J.D.; Venkatachalam, T.K.; Uckun,
F.M. Acta Crystallogr., Sect. C 1999, 55, 2122.
6. Valde´s-Mart´ınez, J.; Herna´ndez-Ortega, S.; Espinosa-Pe´rez, G.;
Presto, C. A.; Hermetet, A.K.; Haslow, K.D.; Ackerman, L.J.;
Szczepura, L.F.; Goldberg, K.I.; Glesen, J.M.; Kaminsky, W.;
West, D.X. J. Mol. Struct. 2002, 608, 77.
The methyl groups on the aryl and pyridyl
rings have no influence on the intramolecular
bond between N3 H and N1. This intramolec-
ular hydrogen bond is favored in comparison to
intermolecular hydrogen bond, and is present in
solution and in the solid state. The methyl substi-
tution on the pyridyl ring causes the N2 H bond
to become considerably less polar in solution. The
methyl group alpha to the carbon bonded to the
7. Hermetet, A.K.; Ackerman, L.J.; Swearingen, J.K.; Presto, C.;
Kelman, D.R.; Giesen, J.M.; Goldberg, K.I.; Kaminsky, W.;
West, D.X. J. Chem. Cryst. 2002, 32, 17.
nitrogen affects the intermolecular N2H
S hy-
8. International Tables for X-ray Crystallography; Kluwer
Academic Publishers: Dordrecht, The Netherlands, 1995;
Vol. C.
drogen bond and the geometry of the molecule.
9. Siemens. SHELXTL PCTM, Release 4.1 for Siemens Crystal-
lographic Research System; Siemens Analytical X-ray Instru-
ments, Inc.: Madison, WI, 1990.
Supplementary material
10. Wassmaier, D.; Kirfel, A. Acta Crystallogr., Sect. A 1995, 51,
416.
Crystallographic data (excluding structure
factors) for the structures reported in this paper
have been deposited with the Cambridge Crystal-
lographic Data Center. Copies of available ma-
terial can be obtained, free of charge, on appli-
cation to the Director, CCDC, 12 Union Road,
Cambridge CB21EZ, UK (Fax: +44-(0) 1223-
336033 or e-mail: deposit@ccdc.cam.ac.uk).
11. Mackay, S.; Edwards, C.; Henderson, A.; Gilmore, C.; Stewart,
N.; Shankland, K.; Donald, A; Mackay, S.; Edwards, C.; M.
Tremayne, M.; Stewart, N.; Shankland, K.; Gilmore, C. MaXus,
A Computer Program for the Solution and Refinement of Crys-
tal Structures and Diffraction Data; University of Glasgow:
Scotland, UK (Nonius BV, Delft, the Netherlands, MacScience
Co. Ltd., Yokohama, Japan), 1998.
12. Etter, M.C. J. Phys. Chem. 1991, 95, 4601.
13. McBride; M.T., Luo, T.-J. M.; Palmore, G.T.R. Crysto. Grow
Des. 2001, 1, 39.