Structural and spectral studies of thiosemicarbazones derived from 3- and 4-formylpyridine and 3- and 4-acetylpyridine

Article abstract of DOI:10.1016/S0022-2860(00)00729-8

Crystal structures of thiosemicarbazones prepared from 3- and 4-formylpyridine and 3- and 4-acetylpyridine are included along with their UV spectra. 4-Formylpyridine thiosemicarbazone has the following structural properties: monoclinic, P2₁÷n, a = 7.2420(5), b = 13.961(1), c = 8.415(1) A?, β = 90.90(1)°, V = 850.7(1) A?³ and Z = 4; for 3-formylpyridine thiosemicarbazone: monoclinic, C2÷c, a = 13.661(2), b = 7.1120(4), c = 19.046(2) A?, β = 107.71(1)°, V = 1762.8(3) A?³ and Z = 8; for 4-acetylpyridine thiosemicarbazone: triclinic, P-1, a = 8.104(3), b = 8.512(2), c = 8.708(3) A?, α = 83.85(0), β = 66.66(0), γ = 62.87(0)°, V = 488.9(3) A?³ and Z = 2; for 3-acetylpyridine thiosemicarbazone monoclinic, P2₁÷a, a = 8.408(1), b = 11.853(2), = c = 9.777(3) A?, β = 97.66(2)°, V = 985.7(4) A?³ and Z = 4. Intramolecular and intermolecular hydrogen bonding are both present. There is a difference in the angles between the mean planes of the pyridine ring and thiosemicarbazone moiety in the two series.

Full text of DOI:10.1016/S0022-2860(00)00729-8

Journal of Molecular Structure 559 (2001) 355–360
www.elsevier.nl/locate/molstruc
Structural and spectral studies of thiosemicarbazones derived from
3- and 4-formylpyridine and 3- and 4-acetylpyridine
a
a
a
a,
b
c
*
I.C. Mendes , L.R. Teixeira , R. Lima , H. Beraldo , N.L. Speziali , D.X. West
a
´
Departamento de Quımica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG Brazil
b
´
Departamento de Fısica, Universidade Federal de Minas Gerais, 31270-901, Belo Horizonte, MG Brazil
cDepartment of Chemistry, Illinois State University, Normal, IL 61790-4160, USA
Received 18 April 2000; accepted 17 August 2000
Abstract
Crystal structures of thiosemicarbazones prepared from 3- and 4-formylpyridine and 3- and 4-acetylpyridine are included
along with their UV spectra. 4-Formylpyridine thiosemicarbazone has the following structural properties: monoclinic, P21/n,
ꢀ
ꢀ 3
a ˆ 7:2420ꢀ5†; b ˆ 13:961ꢀ1†; c ˆ 8:415ꢀ1† A; b ˆ 90:90ꢀ1†Њ; V ˆ 850:7ꢀ1† A and Z ˆ 4; for 3-formylpyridine thiosemicar-
ꢀ
ꢀ 3
bazone: monoclinic, C2/c, a ˆ 13:661ꢀ2†; b ˆ 7:1120ꢀ4†; c ˆ 19:046ꢀ2† A; b ˆ 107:71ꢀ1†Њ; V ˆ 1762:8ꢀ3† A and Z ˆ 8; for
ꢀ
4-acetylpyridine thiosemicarbazone: triclinic, P-1, a ˆ 8:104ꢀ3†; b ˆ 8:512ꢀ2†; c ˆ 8:708ꢀ3† A; a ˆ 83:85ꢀ0†; b ˆ 66:66ꢀ0†;
ꢀ 3
g ˆ 62:87ꢀ0†Њ; V ˆ 488:9ꢀ3† A and Z ˆ 2; for 3-acetylpyridine thiosemicarbazone monoclinic, P21/a, a ˆ 8:408ꢀ1†;
ꢀ
ꢀ 3
b ˆ 11:853ꢀ2†; ˆ c ˆ 9:777ꢀ3† A; b ˆ 97:66ꢀ2†Њ; V ˆ 985:7ꢀ4† A and Z ˆ 4: Intramolecular and intermolecular hydrogen
bonding are both present. There is a difference in the angles between the mean planes of the pyridine ring and thiosemi-
carbazone moiety in the two series. ᭧ 2001 Elsevier Science B.V. All rights reserved.
Keywords: Heterocyclic thiosemicarbazones; 3-substituted; 4-substituted; Crystal structures
1. Introduction
heteroaromatic ring often causes a decrease in activity
presumably due to a lesser ability for coordination [3].
Nevertheless, the literature contains examples of
biologically important bidentate thiosemicarbazones:
p-acetamidobenzaldehyde thiosemicarbazone, known
as thiacetazone, is employed in the clinical treatment
of tuberculosis [4,5]. Therefore, it is important to
continue to prepare and characterize additional thio-
semicarbazones. Here we report the UV spectra and
crystal structures of 3-formyl- and 4-formylpyridine
thiosemicarbazone, H3Fo4DH and H4Fo4DH,
respectively, and 3-acetyl- and 4-acetylpyridine thio-
semicarbazone, H3Ac4DH and H4Ac4DH, respec-
tively (Fig. 1). A structural report of H4Fo4DH
appeared some time ago [6] and our crystal structure
Thiosemicarbazones,
a
class of compounds
possessing a wide spectrum of potential medicinal
applications, have been studied for their antitumor,
antiviral, antibacterial, antimalarial, antifungal, anti-
inflammatory and anti-HIV activities [1,2]. The 2-
heterocyclic thiosemicarbazones have been the
subject of extensive investigation [1, and references
therein]. Changing the point of attachment of the thio-
semicarbazone moiety to the 3- or 4- position on the
* Corresponding author. Tel.: ϩ55-31-3499-5740; fax: ϩ55-31-
3499-5700.
E-mail address: beraldo@apolo.qui.ufmg.br (H. Beraldo).
0022-2860/01/$ - see front matter ᭧ 2001 Elsevier Science B.V. All rights reserved.
PII: S0022-2860(00)00729-8

356
I.C. Mendes et al. / Journal of Molecular Structure 559 (2001) 355–360
1
results are in excellent agreement. The H NMR and
IR spectra of these thiosemicarbazones were reported
recently [7,8].
2. Experimental
The thiosemicarbazones were prepared by refluxing
a solution of the desired aldehyde or ketone with thio-
semicarbazide (all starting materials were purchased
from Aldrich) in ethanol. The crystals were obtained
by slow evaporation of the preparative solutions. The
melting points (ЊC) are as follows: H3Fo4DH: 237–
238; H4Fo4DH: 253–254; H3Ac4DH: 219–221;
H4Ac4DH: 194–196. UV spectra were recorded as
DMSO solutions with a Hewlett–Packard 8453
spectrometer.
2.1. X-ray data collection, structure solution and
refinement
Crystals were mounted on glass fibers and reflec-
tions were collected with a Siemens P4 diffractometer,
MoKa ꢀl ˆ 0:71073 A†: The structures were solved
Fig. 1. Representations of the 3- and 4-formyl- and 3- and 4-acetyl-
pyridine thiosemicarbazones.
ꢀ
Table 1
Crystal data and structure refinement for H4Fo4DH, H3Fo4DH, H4Ac4DH and H3Ac4DH
Compound
H4Fo4DH
H3Fo4DH
H4Ac4DH
H3Ac4DH
Empirical formula
Color; habit
Crystal size (mm)
Crystal system
Space group
C7H8N4S
C7H8N4S
C8H10N4S
C8H10N4S
Yellow, prism
0.40 × 0.30 × 0.10
Monoclinic
Yellow, prism
0.35 × 0.30 × 0.15
Monoclinic
Yellow-orange, prism
0.40 × 0.35 × 0.15
Triclinic
Yellow-orange, prism
0.45 × 0.35 × 0.10
Monoclinic
P21/n (#14)
C2/c (#15)
P-1 (#2)
P21/a (#14)
Unit cell dimensions
˚
a (A)
7.2420(5)
13.961(1)
8.415(1)
90.00
90.90(1)
90.00
13.661(2)
7.1120(4)
19.046(2)
90.00
107.71(1)
90.00
8.104(3)
8.512(2)
8.708(3)
83.85(0)
66.66(0)
62.87(0)
488.9(3)
2
8.408(1)
11.853(2)
9.777(3)
90.00
97.66(2)
90.00
˚
b (A)
˚
c (A)
a (Њ)
b (Њ)
g (Њ)
3
˚
Volume (A )
850.7(1)
4
1762.8(3)
8
985.7(4)
4
Z
Formula weight
180.23
1.407
0.327
180.23
1.358
0.316
194.26
1.320
0.290
194.26
1.336
0.294
Density calculated (g/cm3)
Absorption coefficient (mmϪ1
)
F(000)
376
752
204
408
R
wR2
Goodness-of-fit
R1 ˆ 0.0444
0.0993
2.183
R1 ˆ 0.0413
R1 ˆ 0.0551
R1 ˆ 0.0519
0.1094
1.522
0.1042
0.1345
1.110
2.416
Largest differential peak/hole
0.268/Ϫ0.425
0.192/Ϫ0.178
0.395/Ϫ0.428
0.305/Ϫ0.303
Ϫ3
˚
(eA
)

I.C. Mendes et al. / Journal of Molecular Structure 559 (2001) 355–360
357
Table 2
small difference in the two series; the average C7–
N2 bond is 1.279(2) and 1.287(3) A for the formyl-
˚
Selected bond distances (A) and angles (Њ) for H4Fo4DH,
H3Fo4DH, H4Ac4DH and H3Ac4DH
˚
pyridine and acetylpyridine derivatives, respectively.
˚
The average N2–N3 bond is 1.369(2) A for the
Bond
H4Fo4DH H3Fo4DH H4Ac4DH H3Ac4DH
˚
formylpyridine thiosemicarbazones and 1.386(3) A
C8–S
1.677(3)
1.279(2)
1.371(2)
1.358(2)
1.323(2)
1.693(2)
1.278(2)
1.367(2)
1.357(3)
1.311(3)
1.697(2)
1.290(2)
1.390(2)
1.372(2)
1.330(2)
1.697(2)
1.284(3)
1.384(3)
1.354(3)
1.311(3)
for the acetylpyridine thiosemicarbazones. The small
differences are attributable to the different electronic
effects of the aldehyde hydrogen and ketone methyl
group.
C7–N2
N2–N3
N3–C8
C8–N4
The formylpyridine thiosemicarbazones have
higher melting points compared to the corresponding
acetyl analogues, probably due to the fact that the
angle between the mean plane of the pyridine ring
and the plane involving C(7)–N(2)–N(3)–C(8) is
much smaller in the formylpyridine thiosemicarba-
zones (H3Fo4DH, 9.34(9)Њ; H4Fo4DH, 18.36(8)Њ)
than in the corresponding acetylpyridine thiosemi-
carbazones (H3Ac4DH, 46.3(1)Њ; H4Ac4DH,
50.04(8)Њ). The smaller angle favors molecular
stacking leading to higher density and melting point.
In fact, the calculated densities (H3Fo4DH, 1.358 g/
cm3; H4Fo4DH, 1.407 g/cm3; H3Ac4DH, 1.320 g/
cm3 and H4Ac4DH, 1.336 g/cm3) are in agreement
with closer packing for the formylpyridine thiosemi-
carbazones.
Angle
C7–N2–N3 116.6(1)
N2–N3–C8 118.6(1)
N3–C8–N4 117.0(1)
N3–C8–S
N4–C8–S
116.5(2)
119.4(2)
117.0(2)
119.1(2)
123.9(2)
116.5(5)
118.6(1)
117.5(2)
119.1(1)
123.4(1)
118.2(2)
117.9(2)
117.9(2)
119.2(2)
122.9(2)
119.5(1)
123.5(1)
by direct methods [9] and subsequent difference
Fourier maps, which revealed the position of all
non-hydrogen atoms, and refined on F2 by a full-
matrix least-squares procedure using anisotropic
displacement parameters [10]. Hydrogens on nitro-
gens were located by difference Fourier maps and
refined isotropically and hydrogens attached to
carbons were located in their calculated positions
˚
(C–H 0.93–0.97 A) and refined using a riding
model. Atomic scattering factors were taken from
the International Table for X-ray Crystallography
[11].
Table 3 contains the distances and angles for the
hydrogen bonding of the four thiosemicarbazones.
Three intermolecular hydrogen bonds are observed
for H3Fo4DH, H4Ac4DH and H3Ac4DH and only
two for H4Fo4DH. Taking into consideration the
intermolecular hydrogen bonding, H3Fo4DH,
H4Ac4DH and H3Ac4DH present each a N3–
H3N…S bond and H4FoDH presents no such a
bond, indicating that the melting points are not
much affected by the presence of those interactions.
Of note is the different mode of hydrogen bonding by
the N4H2 function in H3Fo4DH, which is the most
planar of these four thiosemicarbazones.
3. Results and discussion
3.1. Structural characterization
Table 1 has summaries of crystal data and X-ray
data collection, data reduction and structure refine-
ment results for H4Fo4DH, H3Fo4DH, H4Ac4DH
and H3Ac4DH. Selected bond distances and angles
for the four thiosemicarbazones are listed in Table
2. Perspective views for H4Fo4DH, H3Fo4DH,
H4Ac4DH and H3Ac4DH are shown in Fig. 2a–d.
Intramolecular and intermolecular hydrogen bonding
parameters are presented in Table 3 and the mean
plane data are compiled in Table 4.
3.2. Spectral characterization
1
The H NMR spectra, reported previously [7,8],
showed two signals for N4H2 due to one hydrogen
interacting with N2 in each of the compounds. N3H
is found in the 11.65 region for the formylpyridine
thiosemicarbazones, but at ca. d ˆ 10:35 for the acet-
ylpyridine thiosemicarbazones, which is consistent
with hydrogen bonding to DMSO [12] in both cases.
As would be expected, there are not large differ-
ences in the bond distances of the thiosemicarbazone
moieties. However, the imine C7–N2 and, possibly
the N2–N3 bonds, would be expected to show a

358
I.C. Mendes et al. / Journal of Molecular Structure 559 (2001) 355–360
Fig. 2. Perspective view with atom numbering scheme and displacement ellipsoids at 50% probability level of (a) of H4Fo4DH; (b) H3Fo4DH;
(c) H4Ac4DH; (d) H3Ac4DH.

I.C. Mendes et al. / Journal of Molecular Structure 559 (2001) 355–360
359
Table 3
Hydrogen bonding interactions
Compound
H4Fo4DH
D–H…A
d(D–H)
d(H…A)
d(D–H…A)
(D–H…A)
N4–H4B–N2
N4–H4B –N1
0.77(2)
0.77(2)
0.963(6)
2.29(2)
3.064(6)
2.541(6)
2.615(2)
3.530(9)
3.495(7)
107(2)
122(2)
170(2)
N4–H4A–S
H3Fo4DH
H4Ac4DH
H3Ac4DH
N4–H4B–N2
N4–H4A –N1
N3–H3N– S
N4–H4B–S
0.83(3)
2.31(3)
2.624(2)
2.938(6)
3.394(8)
3.448(6)
103(2)
174(2)
167(2)
137(1)
0.889(6)
0.889(6)
0.834(5)
2.052(5)
2.522(6)
2.792(7)
N4–H4B–N2
N4–H4B –N1
N3–H3N– S
N4–H4A–S
0.95(3)
2.33(3)
2.656(2)
3.044(6)
3.530(8)
3.493(7)
99(2)
158(2)
171(2)
171(1)
0.952(7)
0.907(6)
0.945(5)
2.138(6)
2.631(8)
2.557(6)
N4–H4B–N2
N4–H4B –N1
N3–H3N– S
N4–H4A–S
0.99(3)
2.25(3)
2.618(3)
2.951(6)
3.671(6)
3.451(7)
101(2)
157(2)
177(1)
164(2)
0.993(6)
0.857(3)
0.846(6)
2.011(6)
2.815(7)
2.630(3)
The lower field signal indicates a higher acidity for
N(3)H in the formylpyridine thiosemicarbazones.
This same effect has been observed in pyruvaldehyde
bis(thiosemicarbazones), the ketone moiety having a
significantly lower d for the corresponding proton, ca.
9.9, than the aldehyde arm, ca. 11.1 [13].
The UV–visible spectra of all four thiosemicarba-
zones are very similar. An absorption at ca.
36 000 cmϪ1 is assigned to a ring p–pء transition
and the bands in the 30 000–31 500 and 27 000–
28 000 cmϪ1 ranges, are assigned to n–pء transitions
within the thiosemicarbazone moiety, involving mainly
CyN(1) and CyS, respectively [14]. The transition
energies of the formyl thiosemicarbazones are lower
than found for the corresponding acetyl analogues,
probably due to a smaller angle between the thiosemi-
carbazone moiety and the pyridine ring which favors
delocalization in the former (see Table 4).
Supplementary material: Crystallographic data
(excluding structure factors) for the structures
reported in this article have been deposited with
Cambridge Crystallographic Data Centre as supple-
mentary publications numbers 143285 to 143288.
Copies of available material can be obtained on appli-
cation to the Director, CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK.
Table 4
Mean plane deviations and angles between mean planes hydrogen bonding interactions
Plane
Mean deviation
Largest deviation
Angle with previous plane
H4Fo4DH
H3Fo4DH
H4Ac4DH
H3Ac4DH
N1–C2–C3–C4–C5–C6
C7–N2–N3–C8–S–N4
0.0016
0.0313
0.0025 (C6)
0.0569 (N3)
18.36(8)
9.34(9)
50.04(8)
46.3(1)
N1–C2–C3–C4–C5–C6
C7–N2–N3–C8–S–N4
0.0059
0.0115
0.0098 (C3)
0.0172 (N3)
N1–C2–C3–C4–C5–C6
C7–N2–N3–C8–S–N4
0.0102
0.0797
0.0145 (C4)
0.1566 (N2)
N1–C2–C3–C4–C5–C6
C7–N2–N3–C8–S–N4
0.0037
0.0625
0.0051 (C6)
0.1142 (N2)

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I.C. Mendes et al. / Journal of Molecular Structure 559 (2001) 355–360
[6] F.E. Anderson, J.C. Duca, J.W. Scudi, J. Chem. Soc. (1951)
Acknowledgements
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[8] I.C. Mendes, L.R. Teixeira, R. Lima, T.G. Carneiro, H.
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The authors acknowledge the support for their work
from CNPq, Capes and Fapemig.
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