Hydrogen-bonding networks in heterocyclic thioureas

Article abstract of DOI:10.1007/s10870-007-9246-1

The synthesis of heterocyclic thioureas from heterocyclic amines with phenyl- or methylisothiocyanate or CS₂ is described. Seven new X-ray crystal structures are reported: In N-(3-pyridyl)-N'-phenylthiourea (Pna2 ₁, a = 10.1453(3), b

Full text of DOI:10.1007/s10870-007-9246-1

J Chem Crystallogr (2007) 37:755–764
DOI 10.1007/s10870-007-9246-1
ORIGINAL PAPER
Hydrogen-Bonding Networks in Heterocyclic Thioureas
Aakarsh Saxena Æ Robert D. Pike
Received: 31 July 2007 / Accepted: 30 August 2007 / Published online: 18 September 2007
ꢀ Springer Science+Business Media, LLC 2007
Abstract The synthesis of heterocyclic thioureas from
heterocyclic amines with phenyl- or methylisothiocyanate or
CS2 is described. Seven new X-ray crystal structures are
reported: In N-(3-pyridyl)-N0-phenylthiourea (Pna21, a =
10.1453(3), b = 17.6183(5), c = 6.4787(2), V = 1158.02(6),
Z = 4) hydrogen-bonding results in formation of a 3D net-
workconsisting ofhelices, whichformchannelsparallel to the
c-axis. In N-(4-pyridyl)-N0-phenylthiourea (P21/c, a =
16.9314(3), b = 10.3554(2), c = 13.5152(3), b = 106.5080
(10), V = 2271.96(8), Z = 4, two independent molecules)
hydrogen-bonding results in N–HꢀꢀꢀS bridged dimers and
N–HꢀꢀꢀPy chains, forming a 2D sheet network. In N-
(2-pyrimidyl)-N0-phenylthiourea (P21/c, a = 5.45900(10),
b = 13.8559(2), c = 14.3356(3), b = 94.9800(10), V =
1080.24(3), Z = 4) and N-(2-pyrimidyl)-N0-methylthiourea
(P21/c, a = 8.8159(5), b = 11.2386(5), c = 7.7156(4), b =
95.629(2), V = 760.76(7), Z = 4) pairs of intra- and inter-
molecular N–HꢀꢀꢀN interactions produce dimers. Dimer
formation through N–HꢀꢀꢀS occurs for N-(2-thiazolyl)-N0-
methylthiourea (C2/c, a = 17.9308(3), b = 7.78260(10),
c = 10.8686(2), b = 105.3740(10), V = 1462.42(4), Z = 8).
Two symmetrically disubstituted thioureas were examined:
N,N0-bis(2-pyridyl)thiourea (Fdd2, a = 15.1859(2), b =
30.1654(3), c = 9.44130(10), V = 4324.95(8), Z = 16)
forms intra- and intermolecular N–HꢀꢀꢀPy hydrogen-bonds,
forming a 1D zigzag chain and N,N0-bis(3-pyridyl)thiourea
(P21/c, a = 13.2461(2), b = 6.26170(10), c = 12.3503(2),
b = 96.0160(10), V = 1018.73(3), Z = 4) forms intermolec-
ular N–HꢀꢀꢀPy hydrogen-bonds, resulting in 2D sheets.
Keywords Heterocycle ꢀ Thiourea ꢀ Hydrogen-bonding ꢀ
Network ꢀ Conformer
Introduction
Ureas and thioureas are widely recognized for their ability
to hydrogen-bond. In addition, they can act as ligands in
coordination complexes. This combination has led to their
increasing use in an array of self-assembled network
materials [1, 2]. It is to be expected that incorporation of
heterocyclic rings into thiourea molecules will produce an
extended range of possible H-bonding interactions. A
number of heterocyclic thiourea crystal structures have
been determined [3–9]. However, virtually all of these
structures feature a 2-pyridyl or related ortho-substituted
nitrogen heterocycle. This heteroatom arrangement results
in a highly favorable intramolecular H-bond, as illustrated
in I. A few of the known structures show additional
H-bonding, as represented in II–V. The six known com-
pounds illustrated by II and III add to the ubiquitous
internal H-bond an N–HꢀꢀꢀS interaction, resulting in dimer
formation [3, 5–8]. The ‘‘hydrogen-bonded’’ NꢀꢀꢀS dis-
˚
tances in these species range from 3.256 to 3.379 A.
Although relatively weak, these thiocarbonyl H-bonding
interactions are fairly common when the C=S is part of a
resonance delocalized system and therefore is relatively
˚
long ([ca. 1.65 A) [10]. Compounds VI and V make use of
pendant heteroatom groups to form H-bonded chains, with
the latter incorporating an H-bonded water molecule into
the chain [6, 9]. Nevertheless, seven compounds that are
closely related to IV, having pendant furan, thiophene,
2-methylpiperidine, and pyrrolidinone groups, adopt an
internal H-bonding only structure, as illustrated by I [6]. As
part of a study of metal network complexes, we set out to
A. Saxena ꢀ R. D. Pike (&)
Department of Chemistry, College of William and Mary,
Williamsburg, VA 23187-8795, USA
e-mail: rdpike@wm.edu
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Synthesis
synthesize and crystallographically characterize a variety
of heterocyclic thioureas for use as ligands. The aim of the
current study was to identify organic networking patterns
resulting from H-bonding.
N-(3-Pyridyl)-N0-phenylthiourea (1). 3-Aminopyridine
(4.71 g, 50.0 mmol) was dissolved in 60 mL EtOH. Phenyl
isothiocyanate (6.76 g, 50.0 mmol) was added, forming a
clear, colorless solution. The mixture was stirred overnight
under N2 leading to formation of a precipitate. The white
product was isolated by vacuum filtration, was washed with
pentane, and was dried in vacuo (9.62 g, 83.9%). m.p.:
156–158 ꢁC. 1H NMR (400 MHz, CDCl3) d 8.50 (d,
J = 2.4 Hz, 1H, HPy-2), 8.47 (d, J = 4.7 Hz, 1H, HPy-4), 8.07
(d, J = 8.6 Hz, 1H, HPy-6), 7.94 (s, 1H, NH) 7.62 (s, 1H, NH),
7.50 (7, J = 7.8 Hz, 2H, HPh-m), 7.36 (m, 4H, HPy-5, HPh-o,p).
13C{1H} NMR (100 MHz, CDCl3) d 180.76, 146.19, 145.51,
138.29, 136.07, 132.05, 129.28, 126.23, 124.88, 123.25.
Anal. Calcd. for C12H11N3S C, 62.86; H, 4.84; N, 18.33.
Found: C, 62.97; H, 4.87; N, 18.39. IR: 3150 (s, br), 2977
(m, br), 2872 (m, br), 1535 (s), 1511 (s), 1489 (m), 1379 (m),
1231 (m), 1198 (m), 1099 (w), 1024 (m), 735 (m), 710 (m),
691 (m), 647 (m), 615 (m).
Experimental
General
All reagents were purchased from Aldrich or Acros and
were used as received. Melting point data were recorded
on a MelTemp apparatus and are reported uncorrected. C,
H, N analyses were carried out by Atlantic Microlabs
(Norcross, GA). NMR data were recorded on a Varian
Mercury 400 instrument (s = singlet, d = doublet,
t = triplet, br = broad, v br = very broad, J = coupling
constant; Py = pyridyl, Pym = 2-pyrimidyl, Thz = 2-
thiazolyl; for numbering of heterocycles see 1–7). IR
spectra were recorded using a Digilab FTS-7000 series
FTIR as KBr pellets (s = strong intensity, m = medium,
w = weak, br = broad).
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N-(4-Pyridyl)-N0-phenylthiourea (2). 4-Aminopyridine
(1.88 g, 20.0 mmol) was dissolved in 20 mL pyridine.
Phenyl isothiocyanate (3.38 g, 25.0 mmol) was added,
forming a clear, yellow solution. The mixture was stirred
overnight under N2 leading to formation of a precipitate.
The white product was isolated by vacuum filtration,
stirred in water overnight to remove residual 4-amino-
pyridine, and was dried in vacuo (3.54 g, 77.1%). m.p.:
(m), 1426 (m), 1359 (w), 1333 (w), 1213 (m), 1143 (w),
1051 (m), 818 (m), 792 (m), 644 (m).
N-(2-Thiazolyl)-N0-methylthiourea (5). 2-Aminothiazole
(2.50 g, 25.0 mmol) was dissolved in 25 mL pyridine.
Methyl isothiocyanate (2.19 g, 30.0 mmol) was added,
forming a clear, brown solution. The mixture was stirred
overnight under N2. The brown solution was evaporated,
leaving a viscous brown oil which solidified under vacuum.
The light brown product was washed with diethyl ether, and
1
139–141 ꢁC. H NMR (400 MHz, CDCl3) d 9.44 br (s,
1H, NH), 8.76 (br s, 1H, NH), 8.46 (d, J = 4.7 Hz, 2H,
1
was dried in vacuo (3.24 g, 76.9%). m.p.: 164–166 ꢁC. H
H
Py-3,5), 7.71 (d, J = 4.7 Hz, 2H, HPy-2,6), 7.48, (d,
NMR (400 MHz, CDCl3) d 11.00 (br s, 1H, NH), 10.81 (br
s, 1H, NH), 7.32 (d, J = 3.5 Hz, 1H, HThz-5), 6.85 (d,
J = 3.5 Hz, 1H, HThz-4), 3.26 (d, J = 4.7 Hz, 3H, CH3).
13C{1H} NMR (100 MHz, CDCl3) d 178.61, 162.11,
137.80, 111.52, 32.27. Anal. Calcd. for C5H7N3S2 C, 34.66;
H, 4.07; N, 24.25. Found: C, 34.95; H, 4.11; N, 24.06. IR:
3157 (m, br), 3103 (m), 3061 (m, br), 2968 (m, br), 1594 (s),
1561 (s), 1517 (s), 1459 (m), 1359 (w), 1242 (s), 1163 (m),
1112 (w), 1076 (w), 1053 (m), 691 (m), 607 (w).
J = 8.6 Hz, 2H, HPh-o), 7.38 (t, J = 7.4 Hz, 2H, HPh-m),
7.23 (t, J = 7.4 Hz, 1H, HPh-p). 13C{1H} NMR (100 MHz,
CDCl3) d 150.75, 130.61, 129.87, 128.35, 127.42, 125.63,
125.53, 116.49. Anal. Calcd. for C12H11N3S C, 62.86; H,
4.84; N, 18.33. Found: C, 63.05; H, 4.87; N, 18.05. IR:
3160 (s, br), 2992 (m, br), 2951 (m, br), 2926 (m, br),
1593 (s), 1533 (s), 1511 (s), 1485 (s), 1413 (s), 1364 (s),
1287 (m), 1226 (m), 1190 (s), 1004 (w), 777 (s), 692 (m),
642 (m), 628 (m).
N,N0-Bis(2-pyridyl)thiourea
(6).
2-Aminopyridine
N-(2-Pyrimidyl)-N0-phenylthiourea (3). 2-Aminopyrim-
idine (4.76 g, 50.0 mmol) was dissolved in 20 mL
pyridine. Phenyl isothiocyanate (8.12 g, 60.0 mmol) was
added, forming a clear, yellow solution. The mixture was
stirred overnight under N2 leading to formation of a pre-
cipitate. The white product was isolated by vacuum
filtration, washed with diethyl ether, and was dried in
vacuo (4.82 g, 41.9%). m.p.: 188–191 ꢁC. 1H NMR
(400 MHz, CDCl3) d 12.99 (s, 1H, NH), 9.95 (s, 1H, NH),
8.79 (s, 2H, HPym-3,5), 7.67 (d, J = 7.8 Hz, 2H, HPh-o), 7.43
(7, J = 7.4 Hz, 2H, HPh-m), 7.30 (t, J = 6.3 Hz, 1H, HPym-
4), 7.05 (d, J = 4.7 Hz, 1H, HPh-p). 13C{1H} NMR
(100 MHz, CDCl3) d 179.03, 157.64, 138.70, 129.02,
126.75, 125.15, 115.67. Anal. Calcd. for C11H10N4S C,
57.37; H, 4.38; N, 24.33. Found: C, 57.58; H, 4.33; N,
24.30. IR: 3209 (m, br), 3173 (m, br), 3028 (m, br), 1593
(m), 1546 (s), 1518 (s), 1443 (m), 1416 (s), 1350 (w), 1195
(m), 1559 (m), 800 (m), 692 (m).
(4.71 g, 50.0 mmol) was dissolved in 20 mL pyridine.
Carbon disulfide (7.71 g, 100 mmol) was added, forming a
clear, yellow solution. The mixture was refluxed overnight
under N2. The solution was concentrated and cooled, pro-
ducing a precipitate. The off-white product was isolated by
vacuum filtration, stirred in water overnight to remove
residual 2-aminopyridine, and was dried in vacuo (4.02 g,
1
69.8%). m.p.: 155–158 ꢁC. H NMR (400 MHz, CDCl3) d
9.4 (v br s, 2H, NH), 8.6 (v br s, 2H, HPy-3), 8.40 (br s, 2H,
H
Py-4), 7.72 (br s, 2H, HPy-6), 7.07 (br s, 2H, HPy-5). 13C{1H}
NMR (100 MHz, CDCl3) d 176.28, 151.52, 146.96 &
145.37 (partially coalesced), 136.79 (coalesced, br), 119.24
& 117.86 (partially coalesced), 115.60 & 111.53 (partially
coalesced). Anal. Calcd. for C11H10N4S1 C, 57.37; H, 4.38;
N, 24.33. Found: C, 57.65; H, 4.29; N, 24.50. IR: 3462 (s,
br), 3235 (m), 1601 (s), 1561 (s), 1524 (s), 1471 (s), 1421
(s), 1351 (s), 1182 (m), 1146 (m), 771 (m).
N,N0-Bis(3-pyridyl)thiourea
(7).
3-Aminopyridine
N-(2-Pyrimidyl)-N0-methylthiourea (4). 2-Aminopyrim-
idine (2.38 g, 25.0 mmol) was dissolved in 25 mL
pyridine. Methyl isothiocyanate (2.56 g, 35.0 mmol) was
added, forming a clear, yellow solution. The mixture was
stirred overnight under N2. The red-brown solution was
concentrated and cooled, producing a precipitate. The off-
white product was isolated by vacuum filtration, was
washed with diethyl ether, and was dried in vacuo (3.24 g,
(4.71 g, 50.0 mmol) was dissolved in 20 mL pyridine.
Carbon disulfide (7.71 g, 100 mmol) was added, forming a
clear, yellow-brown solution. The mixture was stirred
overnight under N2 leading to formation of a precipitate.
The white product was isolated by vacuum filtration,
washed with diethyl ether, and was dried in vacuo (4.36 g,
1
75.7%). m.p.: 169–172 ꢁC. H NMR (400 MHz, CDCl3) d
10.10 (s, 2H, NH), 8.63 (d, J = 2.7 Hz, 2H, HPy-2), 8.36 (d,
J = 3.6 Hz, 2H, HPy-4), 7.95 (d, J = 8.2 Hz, 2H, HPy-6),
7.39 (dd, J = 8.2, 4.7 Hz, 2H, HPy-5). 13C{1H} NMR
(100 MHz, CDCl3) d 180.64, 145.32, 145.27, 135.82,
131.38, 123.07. Anal. Calcd. for C11H10N4S1 C, 57.37; H,
4.38; N, 24.33. Found: C, 57.61; H, 4.39; N, 24.29. IR:
3208 (w), 3166 (w), 3208 (w), 2978 (s, br), 2936 (m, br),
2787 (w, br), 1599 (m), 1582 (m), 1535 (m), 1473 (w),
1
76.9%). m.p.: 212–214 ꢁC. H NMR (400 MHz, CDCl3) d
11.12 (s, 1H, NH), 9.99 (s, 1H, NH), 8.77, (br s, 2H, HPym-
3,5) 7.00 (t, J = 4.7 Hz, 1H, HPym-4), 3.29 (t, J = 4.7 Hz,
3H, CH3). 13C{1H} NMR (100 MHz, CDCl3) d 180.78,
157.88, 115.37, 32.66. Anal. Calcd. for C6H8N4S C, 42.84;
H, 4.79; N, 33.31. Found: C, 42.94; H, 4.83; N, 33.15. IR:
3230 (m, br), 3165 (w, br), 3071 (m, br), 1578 (s), 1529
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1417 (s), 1314 (m), 1276 (s), 1254 (m), 1024 (w), 762 (w),
719 (s), 640 (w).
of phenyl- or methylisothiocyanate with various amino-
heterocycles (ArNH2) according to reaction (1) [2, 8,
15–17]. In all cases, good yields were realized. The two
homo-substituted thioureas, 6 and 7 were produced by the
reaction of aminopyridines with carbon disulfide in pyri-
dine according to reactions (2) and (3) [17, 18]. While
2- and 3-aminopyridine produced compounds 6 and 7, the
attempted reaction with 4-aminopyridine produced a yel-
low solid that was provisionally identified based upon
NMR data as 4-aminopyridinium N-(4-pyridyl)dithiocar-
bamate [16]. Thus, reaction (3) failed to occur presumably
due to relatively weak nucleophilicity of 4-aminopyridine.
X-ray Crystallography
X-ray quality crystals were grown by slow evaporation or
diethyl ether layering of acetone solutions. Crystals were
mounted on glass fibers. All measurements were made
using graphite-monochromated Cu Ka radiation on a
Bruker-AXS three-circle diffractometer, equipped with a
SMART APEX II CCD detector. Initial space group
determination was based on a matrix consisting of 120
frames. The data were reduced using SAINT+ [11], and
empirical absorption correction applied using SADABS
[12].
ArNH2 þ RN¼C¼S ! ArNHCð¼SÞNHR
PyNH2 þ CS2 ! PyNHCð¼SÞSH
ð1Þ
ð2Þ
ð3Þ
Structures were solved using direct methods. Least-
squares refinement for all structures was carried out on F2.
The non-hydrogen atoms were refined anisotropically. All
hydrogen atoms in each structure were located by standard
difference Fourier techniques and were refined with iso-
tropic thermal parameters. Structure solution, refinement
and the calculation of derived results were performed using
the SHELXTL package of computer programs [13].
Packing diagrams were produced using Mercury [14].
Details of the X-ray experiments and crystal data are
summarized in Table 1. Selected bond lengths and bond
angles are given in Table 2, a summary of hydrogen-bonds
is provided in Table 3, and a summary of interplanar
angles is found in Table 4.
PyNH2 þ PyNHCð¼SÞSH ! ðPyNHÞ2C¼S þ H2S
N-(3-Pyridyl)-N0-phenylthiourea, 1 and N-(4-Pyridyl)-
N0-phenylthiourea, 2
In contrast to the intramolecular H-bonding behavior uni-
formly encountered for ortho-heterocylic thioureas,
placement of the pyridine nitrogen at the 3- or 4-position
produced only intermolecular hydrogen-bonds, resulting in
the formation of extended networks. Compound 1 crystal-
lizes in the non-centrosymmetric orthorhombic space
group Pna21 (Flack parameter = 0.022(18)). A molecular
diagram is shown in Fig. 1 and a packing diagram
emphasizing the 3D H-bonding network is shown in Fig. 2.
As is the case with each of the compounds described
herein, the molecular structure of 1 is unremarkable. Also,
like all but one of the disubstituted thiourea structures
reported herein, one thiourea substituent (the phenyl ring)
is oriented toward the thiocarbonyl carbon and the other
toward the sulfur (EZ conformation). The two ring planes
lie at fairly large angles to one another and also to the plane
defined by the thiourea core (NC(S)N), see Table 4. The
bond lengths and angles within the thiourea core are rela-
tively symmetrical. Two intermolecular H-bonds are seen
in 1: N1–HꢀꢀꢀN3 (TuꢀꢀꢀPy, Tu = thiourea) and N2–HꢀꢀꢀS1
(TuꢀꢀꢀTu) (see Table 3 for H-bonding distances). The rel-
atively long NꢀꢀꢀS distances encountered for compounds 1,
2, and 5 are facilitated by resonance lengthening of C=S
(see Table 2), [10] and are similar to those of previously
determined thiourea dimers [3, 5–8]. Helices, consisting of
six H-bonded molecules were found to propagate parallel
to the c-axis forming channels. The phenyl rings lie within
Results and Discussion
Synthesis
The five heterocyclic-substituted thioureas, 1–5 were syn-
thesized through the reactions
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a
˚
Table 2 Selected bond distances (A) and angles (ꢁ)
1
2
3
4
5
6
7
C1–S1
1.6990(19)
1.332(3)
1.6950(14), 1.6985(14)
1.3505(18), 1.3565(17)
1.3481(18), 1.3375(18)
1.4144(18), 1.4101(17)
1.4234(18), 1.4301(18)
117.30(12), 116.68(12)
123.11(10), 123.60(10)
119.54(10), 119.69(10)
125.48(12), 125.21(12)
129.43(12), 128.30(12)
1.6813(14)
1.3807(17)
1.3350(18)
1.3900(18)
1.4264(17)
116.66(12)
119.57(10)
123.76(10)
129.64(12)
125.36(12)
1.6858(13)
1.3878(16)
1.3181(17)
1.3842(16)
1.4557(16)
117.40(11)
118.66(9)
1.6932(15)
1.375(2)
1.6736(13)
1.3501(16)
1.3737(16)
1.4010(15)
1.4045(18)
114.59(12)
126.99(10)
118.42(9)
1.6763(14)
1.3644(18)
1.3654(18)
1.4175(18)
1.4123(18)
111.55(12)
124.52(11)
123.93(11)
124.41(13)
123.73(12)
C1–N1
C1–N2
1.344(2)
1.325(2)
N1–C2
1.435(2)
1.379(2)
N2–CX
1.424(2)
1.452(2)
N1–C1–N2
N1–C1–S1
N2–C1–S1
C2–N1–C1
CX–N2–C1
a
118.66(18)
121.96(15)
119.36(15)
122.11(16)
127.85(19)
117.14(13)
119.00(11)
123.86(12)
127.09(13)
123.57(14)
123.94(9)
129.54(11)
124.06(11)
131.16(12)
130.69(11)
CX = C7 for 1, 2, 6, and 7; C6 for 3 and 4; C5 for 5
˚
Table 3 Hydrogen-bond distances (A) and Angles (ꢁ)
Compound D–HꢀꢀꢀA
HꢀꢀꢀA dist. DꢀꢀꢀA dist. D–HꢀꢀꢀA angle
1
N2–H2ꢀꢀꢀS1a
2.47(2)
3.329(2)
164.7(19)
N1–H1ꢀꢀꢀN3b
2.14(2)
2.936(2)
159(2)
2
N1–H1NꢀꢀꢀN6c 2.109(19) 2.8305(17) 154.1(17)
N2–H2NꢀꢀꢀS1d 2.527(19) 3.3434(12) 162.0(16)
N4–H4NꢀꢀꢀN3 2.059(19) 2.8498(17) 156.6(16)
N5–H5NꢀꢀꢀS2e 2.449(19) 3.3274(12) 165.2(15)
Fig. 1 Molecular structure of 1. Thermal ellipsoids shown at 50%
3
4
5
6
7
N1–H1ꢀꢀꢀN4f
N2–H2ꢀꢀꢀN3
2.265(19) 3.0824(16) 177.8(16)
1.926(19) 2.6399(16) 140.7(17)
these channels. The helices are tiled together with pairs of
molecules producing junctions between them. Curiously,
the oxygen analog of 1, N-(3-pyridyl)-N0-phenylurea
reveals a ZZ conformation in the crystal structure and
shows no H-bonding [19].
N2–H2NꢀꢀꢀN3 1.966(19) 2.6578(16) 139.3(18)
N1–H1NꢀꢀꢀN4g 2.302(17) 3.0943(16) 171.1(13)
3.3184(14) 169.2(18)
N1–H1NꢀꢀꢀS1h 2.52(2)
N2–H2NꢀꢀꢀN3 2.000(19) 2.6911(18) 140.9(17)
2.234(19) 3.0779(14) 170.3(16)
N2–H2ꢀꢀꢀN3i
N1–H1ꢀꢀꢀN4
1.87(2)
N2–H2NꢀꢀꢀN4j 2.13(2)
2.6534(16) 144.7(18)
2.9526(18) 167.5(17)
3.0728(18) 163.7(16)
a
N1–H1NꢀꢀꢀN3k 2.28(2)
Symmetry transformations used to generate equivalent atoms: –x, –
b
y + 1, z + 1/2; x + 1/2, –y + 1/2, z; x,y–1,z; –x, –y + 1, –z + 2; –
c
d
e
x + 1, –y + 2, –z + 1; –x + 1, –y + 2, –z + 1; g–x + 1, –y, –z;
f
h
–
x + 2, y, –z + 3/2; x + 1/4, –y + 3/4, z–1/4; x, –y + 3/2, z–1/2; kx,
y + 1, z
i
j
Compound 2 crystallizes in the monoclinic space group
P21/c. A molecular diagram is shown in Fig. 3 and a
packing diagram with H-bonding emphasized is shown in
Fig. 4. Two independent molecules are present in structure.
In similar fashion to 1, compound 2 forms a symmetrical
thiourea core with an EZ conformation (pyridyl is oriented
toward sulfur in this case) and shows large interplanar
angles between the various combinations of the rings and
the thiourea core (Table 4). Pairs of intermolecular
H-bonds are formed, one pair for each independent mole-
cule: N1–HꢀꢀꢀN6, N4–HꢀꢀꢀN3 (TuꢀꢀꢀPy) and N2–HꢀꢀꢀS1,
N5–HꢀꢀꢀS2 (TuꢀꢀꢀTu). All H-bonds are roughly coplanar,
producing a flat 2D sheet structure. The sheets are
Table 4 Interplanar angles (ꢁ)
Compound Ring 1–ring 2a Ring 1–NC(S)Na Ring 2–NC(S)Na
1
2
51.09(6)
86.22(6)
64.62(6)
88.58(5),
82.15(5)
46.09(6),
55.62(4)
58.59(4),
48.87(6)
3
4
5
6
7
a
68.48(3)
–
5.91(6)
1.94(6)
5.23(7)
20.91(5)
57.73(4)
66.22(3)
–
–
–
24.16(6)
72.21(4)
8.03(7)
56.99(4)
Ring 1 is the heterocyclic ring in 1–5. Ring 2 is the phenyl in 1–3
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J Chem Crystallogr (2007) 37:755–764
761
N-(2-Pyrimidyl)-N0-Phenylthiourea, 3, N-(2-
Pyrimidyl)-N0-Methylthiourea, 4, and N-(2-Thiazolyl)-
N0-Methylthiourea, 5
Each of these heterocyclic thioureas features an ortho-
nitrogen. As a result each compound displays an internal
H-bond, such as has been seen for related species (see
above). Since intramolecular H-bonding requires an E
conformation, all three molecules crystallize as EZ con-
formers. In contrast to most of the known ortho-
heterocyclic thioureas, 3–5 all form H-bonded dimers.
Compound 3 crystallizes in P21/c. A molecular diagram of
the H-bonded dimer, shown in Fig. 5, reveals both an
internal H-bond, N2–HꢀꢀꢀN3 (TuꢀꢀꢀPym) and an intermo-
lecular H-bond, N1–HꢀꢀꢀN4 (TuꢀꢀꢀPym). An analogous
dimeric structure is exhibited by 4, which crystallizes in
P21/c, see Fig. 6. Dimers are also formed by 5, which
crystallizes in the monoclinic space group C2/c. However,
in contrast to compounds 3 and 4 which form dimers
through N–HꢀꢀꢀN interactions, compound 5 forms dimers
through N2–HꢀꢀꢀS2 (TuꢀꢀꢀTu), see Fig. 7. The expected
internal N1–HꢀꢀꢀN3 (TuꢀꢀꢀThz) H-bond is also present. In
addition, there is a close interaction between S1 and S2 of
Fig. 2 Hydrogen bonding network and packing diagram for 1.
Hydrogen atoms omitted for clarity
˚
3.6279(5) A. Compound 5 fails to form H-bonds to either
of the thiazole ring heteroatoms. Its dimeric structure is
very closely related to that of the known thiazole- and
benzothiazole-substituted thioureas, III [3, 7].
Compounds 3–5 stand apart from the other thioureas
reported herein with respect to their core bond lengths. As
is revealed by the data in Table 2, pairs of thiourea C1–N1
and C1–N2 bonds are of very different lengths in com-
Fig. 3 Molecular structure of 2. Thermal ellipsoids shown at 50%
˚
pounds 3–5 (1.375–1.388 vs. 1.318–1.335 A). In addition,
the N1–C2 and N2–CX (CX = C6 for 3 and 4, CX = C5
for 5) bonds are inequivalent (1.379–1.390 vs. 1.426–1.456
˚
A). Finally, it will be noted from the data in Table 4 that
Fig. 4 Hydrogen bonding network and packing diagram for 2.
Hydrogen atoms omitted for clarity
composed of tiled hexagonal rings constructed from
six 2 molecules. The sheets run parallel to the crystallo-
graphic b-axis and the a,c-diagonal. The analogous urea,
N-(4-pyridyl)-N0-phenylurea, exhibits a Z, Z conformation
and shows only a single N–HꢀꢀꢀN (ureaꢀꢀꢀPy) H-bond,
resulting in a chain structure [19].
Fig. 5 Molecular structure and hydrogen bonding dimer for 3.
Thermal ellipsoids shown at 50%
123

762
J Chem Crystallogr (2007) 37:755–764
N,N0-Bis(2-Pyridyl)thiourea, 6, and N,N0-Bis(3-Pyridyl)
thiourea, 7
These symmetrical dipyridylthioureas both form extended
network structures via H-bonding interactions. Compound
6 crystallized in the non-centrosymmetric orthorhombic
space group Fdd2 (Flack parameter = 0.033(10)). A
molecular diagram is shown in Fig. 8 and a packing dia-
gram emphasizing the 2D H-bonding network is shown in
Fig. 9. A fairly symmetrical thiourea core is connected to
the pyridyl substituents in EZ conformation. Compound 6
shows the expected intramolecular H-bond: N1–HꢀꢀꢀN4
(TuꢀꢀꢀPy). A second, intermolecular, H-bond, N2–HꢀꢀꢀN3
(TuꢀꢀꢀPy) produces a zigzag chain which propagates par-
allel to the a,c diagonal. Compound 6 is the only species
studied herein that has an ortho-substituent on each ring
and therefore can form an intramolecular H-bond with
either ring. This situation should produce equilibrium
1
between EZ and ZE conformers. Indeed, the H and 13C
NMR signals (except for those of the thiocarbonyl and ipso
ring carbons) are greatly broadened at room temperature,
indicating that interchange between the conformers is
occurring at an intermediate rate in solution at room
temperature.
Fig. 6 Molecular structure and hydrogen bonding dimer for 4.
Thermal ellipsoids shown at 50%
Compound 7 crystallized in P21/c, forming a H-bonded
sheet which propagates parallel to the b,c-plane. The
molecular diagram for 7, shown in Fig. 10, reveals the only
ZZ molecular conformation reported herein. The packing
diagram, highlighting H-bonding networking, is shown in
Fig. 11. The 2D network structure of 7 results from two
sets of TuꢀꢀꢀPy interactions analogous to those that produce
a 1D chain in 6: N1–HꢀꢀꢀN3 and N2–HꢀꢀꢀN4. However, in
the case of 7 both H-bonding interactions are geometrically
forced to form intermolecularly and propagate in mutually
perpendicular directions: parallel to the b- and c-axes. The
sheets in 7 are not flat since the individual molecules
are oriented at an angle of about 70ꢁ to the sheet plane.
The sheets are comprised of bowl-shaped four-molecule
H-bonded units which are tiled together.
Fig. 7 Molecular structure and hydrogen bonding dimer for 5.
Thermal ellipsoids shown at 50%
the heterocyclic rings in 3–5 are nearly coplanar with the
thiourea core. These observations, taken together, are almost
certainly the result of contributions from resonance forms
30–50. Such resonance contributions are facilitated by the
presence of an intramolecular H-bond in each compound.
A monohydrate of 6 (6•H2O) has previously been
reported [9]. It shows an EZ conformation. Interestingly,
and in contrast to all of the diarylthioureas reported herein
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J Chem Crystallogr (2007) 37:755–764
763
Fig. 8 Molecular structure of 6. Thermal ellipsoids shown at 50%
Fig. 11 Hydrogen bonding network and packing diagram for 7.
Hydrogen atoms omitted for clarity
consisting of both intra- and intermolecular H-bonding.
However, the latter connects the thiourea nitrogen to the
water of hydration, and a second intermolecular H-bond
connects the water to a pyridyl ring. Thus, a zigzag chain
results, in somewhat analogous fashion to 6. Like structures
6 and 6•H2O, N,N0-bis(2-pyridyl)urea exists in the EZ
conformation and has an internal H-bond [20]. However, in
contrast to 6 and 6•H2O, it forms dimers via intermolecular
N–HꢀꢀꢀO (ureaꢀꢀꢀurea), instead of producing a chain. Like
the thiourea 7, N,N0-bis(3-pyridyl)urea adopts a ZZ con-
formation [21]. Although the interplanar angle between the
two rings in the urea is only about 12.2ꢁ (versus 72.21(4)ꢁ
for 7), nevertheless, like the 7 molecules, the ureas form
two sets of ureaꢀꢀꢀPy H-bonds running in roughly perpen-
dicular directions. These interactions result in formation of
a sheet structure closely related to that of 7. The urea
molecules lie at an angle of about 45ꢁ to the overall
H-bonded sheet.
Fig. 9 Hydrogen bonding network and packing diagram for 6.
Hydrogen atoms omitted for clarity
Conclusions
The use of 3- or 4-pyridyl groups in thioureas serves to
produce 1D, 2D or 3D networked products through
intermolecular hydrogen-bonding. 2-Pyridyl, 2-pyrimidyl,
and 2-thiazolyl groups lead to the formation of
dimers containing both intra- and intermolecular hydro-
gen bonds.
Supplementary Material
Fig. 10 Molecular structure of 7. Thermal ellipsoids shown at 50%
Tables of atomic coordinates for each structure are
available as supplementary material. CCDC 655874–
655880 contain the crystallographic data for this paper.
These data can be obtained free of charge by e-mailing
(see Table 4), both rings and the thiourea core in 6•H2O
are virtually coplanar (\5ꢁ interplanar angles). The
H-bonded structure of 6•H2O is analogous to that of 6,
123

764
J Chem Crystallogr (2007) 37:755–764
(c) Kaminsky W, Goldberg KI, West DX (2002) J Mol Struct
605:9
6. Venkatachalam TK, Sudbeck E, Uckun FM (2004) J Mol Struct
687:45
7. Tellez F, Cruz A, Lopez-Sandoval H, Ramos-Garcia I, Gayosso
M, Castillo-Sierra RN, Paz-Michel B, Noth N, Flores-Parra A,
Contreras R (2004) Eur J Org Chem 4203
8. Tsogoeva SV, Hateley MJ, Yalalov DA, Meindl K, Weckbecker
C, Huthmacher K (2005) Bioorg Med Chem 13:5680
9. Zhong H-P, Long L-S, Huang R-B, Zheng L-S, Ng SW (2003)
Acta Crystallogr Sect C 59:o1596
data_request@ccdc.cam.ac.uk or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge, CB2 1EZ UK; Fax +44(0)1223-336033;
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgement This research was supported in part by donors
of the American Chemical Society Petroleum Research Fund (44891-
B3). We are indebted to NSF (CHE-0443345) and the College of
William and Mary for the purchase of the X-ray equipment.
10. Allen FH, Bird CM, Rowland RS, Raithby PR (1997) Acta
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