Synthesis, characterisation and crystal structure of 3,5-dimethylpyrazole-1-carbothioic acid amide

Article abstract of DOI:10.1016/j.mencom.2007.11.012

3,5-Dimethylpyrazole-1-carbothioic acid amide was obtained (along with acetyl thiosemicarbazide) by the condensation of acetylacetone with thiosemicarbazide and characterised through X-ray diffraction and spectral studies.

Full text of DOI:10.1016/j.mencom.2007.11.012

Mendeleev
Communications
Mendeleev Commun., 2007, 17, 335–336
Synthesis, characterisation and crystal structure
of 3,5-dimethylpyrazole-1-carbothioic acid amide
Sukhvinder K. Chawla,* Simrat Kaur, Nidhi Gupta and Geeta Hundal
Department of Chemistry, Guru Nanak Dev University, Amritsar, 143005 Punjab, India. Fax: +91 183 225 8820;
e-mail: sukhwinder.c@rediffmail.com
DOI: 10.1016/j.mencom.2007.11.012
3,5-Dimethylpyrazole-1-carbothioic acid amide was obtained (along with acetyl thiosemicarbazide) by the condensation of
acetylacetone with thiosemicarbazide and characterised through X-ray diffraction and spectral studies.
Thiosemicarbazones and their metal complexes have attracted
considerable attention because of their pharmacological applica-
tions.1 Monothiosemicarbazones (monotsc) (RR1)C=N–NH–
C(=S)NH2 (where R and R1 are H, substituted or non-sub-
stituted alkyl or aryl) have been synthesised by a reaction of
thiosemicarbazide (tsc) with a desired aldehyde or ketone.2
However, attempts to prepare dithiosemicarbazones (ditsc) of
1,3-dicarbonyls through similar reactions were unsuccessful.
A mixture of products (acyl thiosemicarbazide, monotsc, ditsc
and pyrazole derivative) were formed,3 which were poorly
characterised because of their low solubility.
S
S
+
O
excess
OH
OH
H2NNH
H2NNH
C
NH2
N
N
C
NH2
1
S
O
S
+
O
C
NH2
Me
C
NH
C
NHNH2
2
excess
Scheme 1
After two days, the intensity of a new signal at d 2.41 was
significantly enhanced at the expense of original Me protons.
However, total methyl protons to olefinic proton ratio is
retained at 6:1. Finally, during the period of one week, both
the methyl signals merge into the central signal, strongly
indicating the equivalence of both the methyl protons.
We reinvestigated the reaction of acetylacetone with tsc.
Earlier, Gingras and coworkers3 identified only acetylthiosemi-
carbazide 2 from the same reaction. The product is expected to
be formed from the cleavage of acetylacetone. However, no
mono, ditsc or pyrazole derivative could be obtained. Simply
by reversing the mode of mixing of reactants, we isolated two
products: new cyclic five-membered 1 and already known 2
(Scheme 1)† from the reaction of acetylacetone with tsc. These
compounds were characterised by elemental and spectral analysis.
The structure of 1 was confirmed by X-ray crystallography.
The hot solution of tsc in dilute HCl on addition to a
methanolic solution of acetylacetone gave white crystalline
It is expected that 1 undergoes hydrolysis to pyrazole deriva-
tive 3 and HNCS on long standing in solution (Scheme 2). The
S
+
HCSN
N
N
C
NH2
N
NH
1
3
Scheme 2
1
product, mp 160 °C. As studied by H NMR (CDCl3) 1 was
found to hydrolyse in solution to 3 (Scheme 2). A freshly
prepared solution of 1 exhibits two singlets at d 2.18 (3H, Me)
and 2.73 (3H, Me), one singlet at d 5.99 (1H, =CH) along
with two exchangable broad singlets at d 7.26 and 8.62 due to
NH2 protons in its H NMR spectrum. The H NMR spectrum
of this compound changes on long standing. A new singlet also
appeared in the centre of two methyl signals at d 2.41 (< 3%).
formation of HNCS from tsc is already known.4 The cleavage
of tsc to a pyrazole derivative has also been observed earlier.
The reaction of 1,3-diphenyl-1,3-propanedione with tsc yields
3,5-diphenylpyrazole along with monotsc.3 Similarly, pyrazoles
are also obtained from the reaction of 1,3-dicarbonyl compounds
with semicarbazides.3,5
It was shown by X-ray diffraction analysis of 1‡ that there
are two crystallographically independent molecules in the unit
cell. They slightly differ from each other in bond distances and
bond angles, specially, for C–S and C–N (amine) distances.
1
1
†
Synthesis of 1. A hot solution of tsc (0.92 g, 10 mmol) in dilute HCl
(2 M, 10 ml) was slowly added to a methanolic solution (10 ml) of acetyl-
acetone (0.51 ml, 5.0 mmol). White crystalline X-ray quality product
separated out after standing overnight in a refrigerator, which was filtered
at the pump washed with cold water and ethanol and dried in a vacuum.
C(11)
C(5)
1
C(9)
C(3)
Yield 40%, mp 160 °C. H NMR (CDCl3) d: 2.18 (s, 3H, Me), 2.73 (s,
3H, Me), 5.99 (s, 1H, =CH), 7.26 (1H, NH, exchanges with D2O) and
8.62 (1H, NH, exchanges with D2O). IR (KBr, n/cm–1): 3386, 3242 and
3153 (N–H stretching), 1598, 1571 (νC=C, νC=N and δN–H), 800 (νC=S).
Found (%): C, 46.4; H, 5.2; N, 26.6. Calc for C6H9N3S (%): C, 46.5; H,
5.8; N, 27.1.
Synthesis of 2. Reversing the mode of addition of the reactants under
analogous conditions resulted in the formation of 2, mp 181 °C. IR
(KBr, n/cm–1): 3384–3134 (br., νN–H), 1640–1620 (νC=O),6 817 (νC=S),
1545 (νC=C and νC=N). Found (%): C, 27.3; H, 5.7; N, 31.9. Calc. for
C3H7N3OS (%): C, 27.1; H, 5.3; N, 31.5.
C(8)
N(2)
N(1)
C(4)
S(1)
C(2)
C(1)
N(5)
N(4)
C(7)
C(6)
N(3)
C(12)
C(10)
N(6)
1A
1B
Figure 1 ORTEP drawing of two independent molecules of 1 showing
their labelling scheme.
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© 2007 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2007, 17, 335–336
Table 1 Important H-bonding interactions in compound 1.
a
b
Type of interaction
X···Y
H···Y
ÐX–H···Y
N(3)–H(31)···N(2)
N(6)–H(61)···N(5)
N(3)–H(31)···N(5i)
N(6)–H(61)···N(2i)
N(3)–H(32)···S(2ii)
N(6)–H(62)···S(2iii)
2.594(5)
2.618(4)
3.178(4)
3.158(4)
3.459(4)
3.441(3)
2.04
2.21
2.56
2.34
2.64
2.55
119
105
127
139
158
164
Figure 3 Formation of N(6)···S(2) H-bonded centrosymmetric layers and
a cavity down the c axis.
Molecule 1A (lower atom numbers, Figure 1) has a C–S bond
length 0.02 Å shorter and a C–N bond length 0.01 Å longer
than the corresponding distances in molecule 1B (higher atom
numbers, Figure 1). All bond distances and bond angles are
within the expected ranges. The two molecules are rotated by
almost 50° with respect to each other. The heterocyclic rings in
both the molecules are planar and make dihedral angles of 8°
and 12° with their respective thioamide groups.
In the unit cell, the molecules of 1 are held to each other by
strong inter- and intramolecular H-bonding interactions. Both
the thioamide nitrogens N(3) and N(6) act as H-bond donors
whereas S(2), N(2) and N(5) are behaving as H-bond acceptors
(Figure 1). The amine nitrogen N(3) of molecule 1A acts as a
triple H-bond donor forming one intramolecular H-bond with
the ring nitrogen N(2) and two intermolecular H-bonds with N(5)
and S(2) of molecule 1B (Figure 2, Table 1). Similarly, the amine
nitrogen N(6) of molecule 1B is behaving as a triple H-bond
donor with one intramolecular bond to its ring nitrogen N(5) and
one intermolecular H-bond to N(2) of molecule 1A. However,
its second intermolecular H-bond is also with the sulfur atom
S(2) of its own thioamide group. Thus, S(1) of molecule 1A is
not undergoing any H-bonding interaction except for a weak
intramolecular C(6)–H(6A)···S(1) interaction. The corresponding
C(12)···S(2) interaction is also present there. These interactions
[except for N(6)···S(2)] give rise to the formation of layers
down the c axis. These layers are held to each other by the
N(6)–H(62)···S(2) intermolecular interaction (Figure 3). In the
centre of each layer, an H-bonded cavity is formed. Apart from
these H-bonding interactions, two centrosymmetrically related
molecules 1A show face-to-face π–π interactions between them
with a centre-to-centre distance of 3.77 Å. The closest distance
between two centrosymmetric molecules 2 is 4.93 Å.
Therefore, the addition of acetylacetone to the hot solution
provides a facile method for the synthesis of pyrazole-1-carbo-
thioic acid amide.
Simrat Kaur and Nidhi Gupta are indebted to Guru Nanak
Dev University for providing financial assistance.
References
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Figure 2 Important H-bonding interactions down the a axis.
‡
X-Ray diffraction data for 1. At 293 K crystals of C6H9N3S (M =
= 155.22) are triclinic, space group PI, a = 8.461(5), b = 9.393(5) and
c = 10.994(5) Å, a = 69.70(5)°, b = 73.21(5)° and g = 76.85(5)°, V =
= 776.6(7) Å3, Z = 2, dcalc = 1.328 g cm–3; m = 0.343 mm–1. Crystal size,
0.15×0.19×0.10 mm. The data were collected on a Siemens P4 diffracto-
meter with graphite monochromated MoKα radiation (l = 0.71609 Å),
2.03 < q < 25.0°, 0 < h < 9, –10 < k < 10. The structure was solved by
direct methods and subsequent difference Fourier syntheses and refined
by full-matrix least-squares on F2 with SHELXLTL.7 Lorentz and polariza-
tion corrections were applied, but no absorption correction was applied.
All hydrogens were attached geometrically and were not refined. An
anisotropic refinement for all the non-hydrogen atoms finally converged
with a R factor of 0.0511 for observed and 0.0573 for all reflections. The
H-bonding calculations, torsion and dihedral angles and plane were
calculated using PARSI.8
CCDC 611159 contains the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
For details, see ‘Notice to Authors’, Mendeleev Commun., Issue 1, 2007.
Received: 14th March 2007; Com. 07/2890
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