Synthesis, crystal structural characterization and biological properties of thiosemicarbazones of schiff bases derived from 4-Acyl-2-pyrazoline-5-one

Article abstract of DOI:10.1155/2011/826392

A novel synthesis, single crystal and biological activity of 4-acylthiosemicarbazone-3-methyl-1-(4'-methylphenyl)-2-pyrazolin-5-one by condensation of 4-acyl-3-methyl-1-(4'-methylphenyl)-2-pyrazolin-5-one with thiosemicarbazide was carried out. The compou

Full text of DOI:10.1155/2011/826392

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
http://www.e-journals.net
2011, 8(4), 1820-1831
Synthesis, Crystal Structural Characterization and
Biological Properties of Thiosemicarbazones of Schiff
Bases Derived from 4-Acyl-2-pyrazoline-5-one
ARJUNSINH RANA*, NAYAN PAREKH§,
HARISH DABHI§, DIPAK BHOI# and NIRAJ KUMARI
*Department of Chemistry
Navajivan Science College, Dahod-389151, Gujarat, India
§Torrent Research Centre
Village Bhat, Ahmedabad-382428, Gujarat, India
#Department of Chemistry
J & J Science College, Nadiad-387001, Gujarat India
Banaras Hindu University (BHU), Varanasi -221005, India
dr.arjunshinrana@yahoo.co.in
Received 26 July 2010; Accepted 15 October 2010
Abstract: A novel synthesis, single crystal and biological activity of
4-acylthiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one
by condensation of 4-acyl-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one with
thiosemicarbazide was carried out. The compounds were characterized on the basis
of elemental analysis, IR, 1H NMR, Mass, DSC and 13C NMR spectral data. The
compounds were tested for their antibacterial activity against various gram +ve and
-ve bacteria. The results were compared with the marketed drugs. The crystal
structure was determined by single x-ray diffraction. 4-Acetyl thiosemicarbazone-
3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one(AcPTMP-ths) crystallizes in the
monoclinic system, space group P21/n with a=6.0828(7)Å, b=29.547(4)Å,
c=7.9101(15)Å, α=90°, β=95.602(15)°, γ=90°, V=1414.9(4) Å3, Z=4, Dc=1.429
mg/m3 and 4-Propionylthiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-
pyrazolin-5-one (PropPTMP-ths) crystallizes in the monoclinic system, space
group P21/c with a=13.5622(10)Å, b=13.3671(12)Å, c=22.151(2)Å, α=90°,
β=93.13(7)°, γ=90°, V=4010.1(6) Å3, Z=8, Dc=1.310 mg/m3. The compounds were
screened for antibacterial properties and exhibited potential activity.
Keywords: 4-Acyl-2-pyrazoline-5-one, Thiosemicarbazone, Biological activity, Single crystal.
Introduction
The chemistry of thiosemicarbazones has received considerable attention in view of their
variable bonding modes, promising biological implications and structural properties1-3.

1821
ARJUNSINH RANA et al.
The structure diversity of thiosemicarbazide based compounds is considerably increased not
only due to the condensation of the different carbonyls but also due to the alkylation of the
different part of the thiosemicarbazide4. Thiosemicarbazone usually act as chelating ligands
with transition metal ion, bonding through the sulphur and hydrazine nitrogen atom.
Thiosemicarbazones and their complexes have received considerable attention because of
their pharmacological activities5. The pyrazolone derivatives have attracted much attention
because of their interesting structural properties and application6-11
.
Thiosemicarbazones can coordinate to metal as neutral molecules or after
deprotonation, as anionic ligands and can adopt variety different coordination modes. The
possibility of their being able to transmit electronic effects between a reduce unit and metal
centre is suggested by the delocalization of the π bonds in the thiosemicarbazone chain12.
Thiosemicarbazone compounds can be converted in to complexes by reaction with metal
ions and the reaction product has very important uses13,6
.
There are different substituted amide bonds (-CONH-) in structure of these compounds,
therefore most of them have good biological activities and there are some reports about their
use as herbicides and bactericides14,24. In order to exploit new type of chetale extracting and
biological active compound, two type of 4-acyl-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-
5-one are used in present study to react with thiosemicarbazide and new compound of
4-acylthiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one are synthesized
and crystallization. Literature survey revels that few 4-acylthisemicarbazones are reported11-16
.
But single crystal and biological studies of 4-acetyl thiosemicarbazone-3-methyl-1-(4`-
methylphenyl)-2-pyrazolin-5-one (AcPTMP-ths), 4-Propionylthiosemicarbazone-3-methyl-1-
(4`-methylphenyl)-2-pyrazolin-5-one (PropPTMP-ths), which have never been reported.
The present study reports synthesis and single crystal study of AcPTMP-ths and
PropPTMP-ths in continuation of our earlier work. Several 4-acyl-3-methyl-1-phenyl-2-
pyrazolin-5-ones were prepared and applied for the separation of the metals14-20,21
.
Preparation of amine substituted of thiosemicarbazones of 4-acyl-3-methyl-(4`-methylphenyl)
-2-pyrazolin-5-ones and their metal complexes work is in progress.
The new compound of pyrazolone thiosemicarbazone (Figure 1) reported in our earlier
paper was synthesized13. As an extension of this work, we herein report the synthesis,
structural characterization and antibacterial activity of compound AcPTMP-ths and
PropPTMP-ths.
R
H3C
NH2
NH
N
S
N
O
N
R = -CH3 and -CH2-CH3
CH3
Figure 1. Pyrazolone thiosemicarbazone
Many 4-acyl derivatives of 1-phenyl-3-methyl-2-pyrazoline-5-one have been prepared
and applied for the metal complexes. The reaction pyrazolone with acetyl chloride and
propionyl chloride were carried out under the ordinary condition mentioned below.

Synthesis, Crystal Structural Characterization
1822
Reaction formulas are as follow in Scheme 1 and the reaction 4-acyl-2-pyrazoline-5-one
with thiosemicarbazide produce Schiff base11,21-23 was carried out in alcohol such as ethanol
or methanol at reflux temperature and crystallization by aqueous alcohol for purification as
shown Scheme 2. Reaction formulas are as follow in scheme 2 A yellow prismatic crystals
of the titled compounds obtained.
R
H3C
H3C
O
N
N
O
O
Calcium hydroxide
Dioxane & at reflux
N
N
R
Cl
+
O
R = -CH3 and -CH2-CH3
CH3
CH3
R = -CH3 and -CH2-CH3
Scheme 1
R
R
S
H3C
H3C
O
N
NH
NH2
S
N
N
O
O
Alcohol
N
N
H2N
NH
+
NH2
Heat at reflux
CH3
CH3
R = -CH3 and -CH2-CH3
R = -CH3 and -CH2-CH3
Scheme 2
Experimental
Reagent grade and pure (HPLC) grade solvents and chemicals were used during the
experiments. 1-(Phenyl-4-methyl)-3-methyl-2-pyrazoline-5-one (PTMP) was provided from
Prima chemicals (Ahmedabad, India) as free sample. Acetyl chloride, propionyl chloride,
calcium hydroxide, acetic acid, 4-methylphenyl hydrazine, methanol, strong hydrochloric
acid, thiosemicarbazide dioxane was purchased from s.d.fine chemicals (India). The
microorganism strains for antibacterial activity were purchased from Pathoteq Biological
Laboratories (India)). Nutrient media (Agar) was purchased from Hi-media
Measurments
The FT-IR spectra were recorded on a Perkin-Elmer infrared spectrophotometer Model 2000
in the range of 4000-400 cm-1 by using KBr pellets (Vaibhav Analytical, Ahmedabad,
India). Elemental analysis (C, H, N and S) was performed on a Perkin-Elmer Model-2400
elemental analyzer (SCICAR, vallabhvidhyanagar, Gujarat (India)). Nuclear magnetic resonance
spectra (1H NMR and 13C-NMR) were recorded on a Bruker -400 MHz, spectrometer using

1823
ARJUNSINH RANA et al.
DMSO-d6 as a solvent (CSMCRI Bhavnagar, India). Single crystal x-ray powder diffraction
analysis done at IIT, Powai, Mumbai.
Preparation of 4-acyl-2-pyrazoline-5-one
Preparation of 3-methyl-1-(4`-methylphenyl)-4-propyl-2-pyrazoline-5-one (PropPTMP)
1,4-Dioxane solution (250 mL) of 3-methyl-1-(4`-methylphenyl)-2-pyrazoline-5-one
(PTMP) (25.0 g) and propionyl chloride (13.25 mL) was refluxed for 2 h with calcium
hydroxide (13.97 g) and cooled to room temperature. Dilute hydrochloric acid (45 mL
o
conc. HCl in 200 mL water), added slowly to the reaction mass at below 25 C. Solid
light yellow to brown product was filtered and washed with water. 3-Methyl-1-(4-
methylphenyl)-4-propyl-2-pyrazoline-5-on (PTMPP) is light yellow powder and its
o
yield is 89%, m.p: 101.19 C.
1H NMR(400MHz, δ ppm, in DMSO-d6) 1.031-2.33(t, 5H, CH2CH3), 2.41(S, 3H,
PZ-CH3), 2.81(S, 2H, NH2), 7.2 ~7.5 (m, 5H,Ph). FTIR (KBr pellets, υ in cm-1) 3432(w)
(N-H), 3292(w)(O-H), 1621(s)(Pz-C=O),1553(s), 1512(s), 1441(s)Ph, 1404(m), 1364(m)
(Pz). Mass 245 M+. Elemental anal. C14H16N2O2; mol.wt: 244.29: calcd. C (68.83%),
H(6.60%), N(11.47%) and found C (68.71%), H(6.656%), N(11.48%). 3-Methyl-1-
(4`-methylphenyl)-4-acetyl-2-pyrazoline-5-one(AcPTMP) is light yellow powder and its
yield is 82%,m.p: 103.14 oC.
1H NMR(400MHz, δ ppm, in DMSO-d6) 2.33(s, 3H, CH3), 2.40(S, 3H, PZ-CH3),
2.39(S, 2H, NH2), 7.2 ~7.5 (m, 5H,Ph). FTIR (KBr pellets, υ in cm-1) 2924(w)(N-H),
2967(w)(O-H), 1635(s)(Pz-C=O), 1552(s), 1510(s), 1441(s)Ph, 1364(m)1369(m)(Pz). Mass
230.8. Elemenatl anal. C13H14N2O2 mol.wt: 230.26: calcd. C (67.81%), H(6.13%),
N(12.17%) and found C (67.67%), H(6.151%) and N(12.15%).
Preparation of 4-acylthiosemicarbazon-2-pyrazoline-5-one
Preparation of 4-propionylthiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-
pyrazolin-5-one (PropPTMP-ths)
Ethanol or methanol solution (250 mL) of 3-methyl-1-(4-methylphenyl)-4-propionyl-2-
pyrazoline-5-one (PropPTMP) (25.0 g, 1 mol) and thiosemicarbazide or N-4-methylthi-
osemicarbazide or 4,4-dimethyl thiosemicarbazide or 4,4-diphenyl thiosemicarbazide
(l.1 mol) was taken and to this reaction mass catalytic amount of acetic acid (~15-20 mL)
was added and refluxed for 3 to 5 h. Cooled to room temperature. Solid light yellow to
brown product was filtered and washed with methanol or ethanol. 4-Propionyl-
thiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one PropPTMP-ths) was
light yellow powder and its yield was 80%. Crystals of the compound was obtained
by slow diffusion from DMF/ methanol solution and was stable in the air for long
time. Attempt to grow crystals of the compound in many different solvents was
unsuccessful.
1H NMR(400MHz, δ ppm, in DMSO-d6): 1.31-2.2(m, 5H, CH2CH3), 2.33(S, 3H,
PZ-CH3), 2.80(S, 2H, NH2), 7.2 ~7.8 (m, 5H,Ph), 10.07(S, 1H, NH-tsc), 12.10(S, 1H,
Pz-NH). 13C NMR(400MHz, δ ppm, in DMSO-d6)164.66(C=S) 146.52(Pz-C=O)
129.03-118.54(Ph) 117.94-136.42(C-N) 18.45(pz- CH3) 14.08(C- CH3) 38.76-40.01(Ph-
CH3). FTIR (KBr pellets, υ in cm-1) 3426(w)(N-H), 3111..2867(br, m), 1627(s)(Pz-C=O),
1540(s), 1510(s), 1459(s)(Ph), 1387(m)(Pz), 1364(s), 1243(s), 822(m) (C=S). MASS: 316
M- Elem. Anal. (%), C15H19N5OS(317.4) : Calc. (%) C(56.76 %) H(6.03%) N(22.06%)
S(10.10%). found (%) C(56.13%) H(6.04%) N(22.65%) S(11.24%). M.p.: 178.88 oC.

Synthesis, Crystal Structural Characterization
1824
4-Acetylthiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-5-one (AcPTMP-ths),
was light yellow powder and its yield was 90%. Crystals of the compound was obtained by
slow diffusion from DMSO/ Methanol solution and was stable in the air for long time.
Attempt to grow crystals of the compound in many different solvents was unsuccessful.
1H NMR(400MHz, δ ppm, in DMSO-d6): 2.29(s, 3H, CH3), 2.5(S, 3H, PZ-CH3), 2.6(S, 2H,
NH2), 7.18 ~7.85(m, 5H,Ph), 10.03(S, 1H, NH-tsc), 12.10(S, 1H, Pz-NH). 13C NMR
(400MHz, δ ppm, in DMSO-d6) 164.82(C=S) 147.73(Pz-C=O) 129.61-118(Ph) 118.51-137.05
(C-N) 17.31(pz- CH3) 14.82(C- CH3) 39.32-40.57(Ph- CH3). FTIR (KBr pellets, υ in cm-1)
3747(w)(N-H), 3214..2865(br, m), 1624(s)(Pz-C=O),1540(s), 1511(s), 1472(s)Ph, 1364(m)
(Pz), 1324(s), 1208(s), 827(m) (C=S). MASS: 304 M+. Elem. Anal. (%), C14H17N5OS
(303.38): Calc. (%) C(55.42%) H(5.65%) N(23.08%) S(10.57%). found C(55.4%) H(5.63%)
N(23.04%) S(10.98%). DSC: 205.28 oC.
Above all ligands are in crystalline form as per X-RPD pattern done on X’pert PRO
Panalytical using Cu, Generator setting-45 kV / 40 m A; Goniometer (Pw3050/60(θ/ θ),
240 mm Gonoimeter radius.
Results and Discussion
The new Schiff base 4-acyl thiosemicarbazone-3-methyl-1-(4`-methylphenyl)-2-pyrazolin-
5-one would be good precursors for metal complexes like lanthanide series and others
metals like Co, Cr, Mn, Mg, Pd, Ni, Fe, Zn, Ca, Hg and As in bidentet or tridentate
1
respectively. We disclosed analytical data like elemental analysis, H NMR, 13C NMR, IR,
Mass spectra, DSC and x-ray powder diffraction for new Schiff base ligands formation
confirmation. The single crystal preparation and biological activity of metal complexes
synthesized from above ligands is in progress.
Structural determination
Chemical shift of hydrogen in the IR spectrum, the υ(N-H) spectral region is broad,
showing the existence of N-H-O hydrogen bond. The band for υ(C=O) at 1628 cm-1 is at
lower wave number than that usually found for carbonyls, reflecting the involvement in
hydrogen bonding with NH of the thiosemicarbazone and pyrazol-5-one compound. In
1H NMR N(1) is easily distinguished from that of N(2) because the latter (7.161 ppm)
appears as a doublet due to that the two hydrogen atom on N(2) are nonequivalent because
one of them is involved in hydrogen bonding, which is consistent with the crystal structure
analysis. The single peak at 8.3 ppm is assignable to the N(1)-H. The single of 10.2 ppm is
not a unit because N(5) share the same hydrogen with O on the neighboring molecule.
Suitable x-ray quality crystals of the compounds AcPTMP-ths & PropPTMP-ths were
grown from dimethylsulfoxide(DMSO) and methanol solvent mixture at room temperature,
and x-ray crystallographic data are recorded by mounting a single-crystal of compound
PropPTMP-ths (0.23x0.21x0.18) mm3 and compound AcPTMP-ths (0.26x0.19x0.15) mm3
on glass fibers. Oxford diffraction XCALIBUR-S CCD area detector diffractometer
equipped with an LN-2 low-temperature attachment was used for the cell determination and
intensity data collection. Appropriate empirical absorption corrections were applied using
multi-scan programs. Monochromated Mo Kα radiation (λ = 0.71073 Å) was used for the
measurements. The crystal structures were solved by direct methods and refined by full
matrix least squares SHELXL-97. Crystallographic data are presented in Table 1 where as
bond length and bond angles are summarized in Table 2. A computational program
PLATON24 was used to study the involvement of weak interactions and corresponding
distances are summarized in Table 3.

1825
ARJUNSINH RANA et al.
Table 1. Summary of crystallographic data for compounds PropPTMP-ths & AcPTMP-ths
Parameters
Formula
M
Crystal system
Temperature
Space group
a/ Å
PropPTMP-ths
C34H50N10O4S4
791.08
Monoclinic, P 21/c
AcPTMP-ths
C14H18N5OS
304.39
Monoclinic
150(2) K
P 21/n
6.0828(7)
29.547(4)
7.9101(15)
90
150(2) K
P 21/c
13.5622(10)
13.3671(12)
b/ Å
c/ Å
α (°)
22.151(2)
90
β (°)
93.013(7)
90
4010.1(6)
95.602(15)
90
1414.9(4)
4
1.429
8708
2494
0.1002
γ (°)
V/ Å3
Z
8
Dc/ mg·m-3
Reflns. collected
Reflns. unique
R(int)
1.310
28743
7054
0.1555
Index ranges
-16<=h<=16
-15<=k<=14
-26<=l<=26
Full-matrix, least squares on F2
0.2059
-7<=h<=7
-35<=k<=35
-9<=l<=9
Refinement method
wR2
0.1531
0.0706
0.900
R1
GoF
0.0846
1.103
Table 2. Selected bond lengths and bond distances for complexes PropPTMP-ths & AcPTMP-ths
PropPTMP-ths
S(1)-C(1)
O(1)-C(6)
N(1)-C(1)
N(1)-H(1N)
N(2)-C(1)
N(2)-N(3)
1.682(6) C(1)-N(1)-H(1N) 115(4)
1.246(6) C(1)-N(2)-N(3) 121.3(4)
O(1)-C(6)-N(4)
O(1)-C(6)-C(5)
N(4)-C(6)-C(5)
N(6)-C(16)-N(7)
N(6)-C(16)-S(2)
N(8)-C(17)-C(18)
O(2)-C(21)-N(9)
N(9)-C(21)-C(20)
126.2(5)
129.1(5)
104.8(4)
117.8(5)
123.7(5)
119.2(5)
125.8(4)
104.9(4)
1.332(7) N(3)-N(2)-H(2)
119.3
0.93(6) C(6)-N(4)-N(5)) 111.9(4)
1.348(7) C(6)-N(4)-C(9) 128.0(4)
1.394(6) C(16)-N(6)-H(2N) 126(4)
S(222)-O(222) 1.484(4) C(17)-N(8)-N(7) 121.3(4)
S(222)-C(333) 1.775(7) C(21)-N(9)-C(24) 128.2(4)
N(4)-N(5)
N(4)-C(9)
1.411(6) N(1)-C(1)-S(1) 123.7(5) O(111)-S(111)-C(111) 106.0(3)
1.422(6) N(2)-C(1)-S(1) 119.0(4) O(111)-S(111)-C(222) 104.8(3)
C(12)-C(14) 1.383(7) N(3)-C(2)-C(5) 116.7(4) C(111)-S(111)-C(222) 97.9(3)
N(7)-N(8)
1.404(6) C(5)-C(2)-C(3) 124.8(5) O(222)-S(222)-C(333) 103.9(3)
AcPTMP-ths
S(1)-C(1)
O(1)-C(5)
N(1)-C(1)
N(2)-N(3)
N(2)-H(2N)
N(4)-N(5)
N(5)-C(6)
C(2)-C(3)
C(14)-H(14)
1.672(5) C(1)-N(1)-H(1N`) 115(4)
1.249(5) H(1N`)-N(1)-H(1N) 122(5)
N(5)-N(4)-C(8))
N(1)-C(1)-S(1)
N(2)-C(1)-S(1)
O(1)-C(5)-N(4)
O(1)-C(5)-C(4)
N(5)-C(6)-C(4)
C(8)-C(9)-C(10)
C(8)-C(9)-H(9)
118.2(3)
123.7(4)
119.4(3)
126.1(4)
129.0(4)
111.5(4)
119.4(4)
120.3
1.331(6)
1.387(5) N(3)-N(2)-H(2N) 135.7(4)
0.96(5) C(2)-N(3)-N(2) 120.4(4)
C(1)-N(2)-N(3) 122.4(4)
1.396(5) C(2)-N(3)-H(3N) 121(3)
1.305(5) N(2)-N(3)-H(3N) 116(3)
1.494(6) C(5)-N(4)-N(5) 112.2(3)
0.9500
C(5)-N(4)-C(8) 129.6(4) H(12A)-C(12)-H(12B)
109.5

Synthesis, Crystal Structural Characterization
1826
Table 3. Selected parameters for weak interactions in complexes 1 & 2
D-H···A
D-H(Å) H···A (Å) D···A(Å) DHA(°) symmetry code
PropPTMP-ths
N(1)-H(1)N'···N(10)
N(1)-H(1)N···S(2)
N(2)-H(2)···O(111)
N(6)-H(2)N···N(5)
N(6)-H(2)N'···S(1)
N(7)-H(7)···O(222)
C(8)-H(8)C···O(2)
C(10)-H(10)···O(1)
C(111)-H(11A)···O(111)
C(111)-H(11B)···O(2)
C(222)-H(22C)···O(222)
C(25)-H(25)···S(2)
C(444)-H(44A)···S(2)
C(444)-H(44C)···O(111)
AcPTMP-ths
0.75(7) 2.27(7) 3.020(7) 175(4)
0.93(7) 2.48(7) 3.394(6) 169(5)
--
x, -1 + y, z
x, 3/2 -y, -½+z
--
x, 1+y, z
1-x, 2-y, 1-z
--
0.88
0.89
0.89
0.88
0.98
0.95
0.98
0.98
0.98
0.95
0.98
0.98
2.13
2.784(6)
131
2.14(7) 2.985(7) 158(6)
2.13(5) 3.417(5) 175(4)
2.06
2.52
2.44
2.31
2.45
2.50
2.41
2.81
2.58
2.762(6)
3.308(6)
3.308(6)
2.286(7)
3.136(7)
3.220(8)
2.943(6)
3.749(7)
3.342(9)
136
138
115
172
127
130
116
161
135
--
1-x,1 -y, 1-z
x,-1+ y, z
1-x,1 -y, 1-z
--
1-x,2 -y, 1-z
1-x,1 -y, 1-z
N(1)-H(1)N···S(1)
N(1)-H(1)N···N(3)
N(1)-H(1)N···O(1)
N(2)-H(2)N···O(1)
C(3)-H(3A)···N(4)
C(9)-H(9)···N(5)
0.79(5) 2.84(5) 3.449(5) 136(5)
0.79(5) 2.38(5) 2.693(6) 105(5)
0.79(6) 2.23(6) 2.951(6) 152(5) ½+x, ½ -y, ½+z
-1+x, y, z
--
0.88(5) 2.08(6) 2.947(5) 170(5)
1+x, y, z
1+ x, y, z
0.98
0.95
0.95
2.59
2.38
2.30
3.478(6)
2.742(6)
2.932(5)
151
102
124
--
--
C(14)-H(14)···O(1)
The molecular structure along with the crystallographic numbering scheme of
PropPTMP-ths is given in Figure 2. The compound crystallizes in monoclinic crystal system
with space group P21/c. Each unit consists of two asymmetric molecules of ligand along
with two molecules of co-crystallized solvent DMSO molecule. The pyrazolone ring
(N5-N4-C6-C5-C7) and phenyl (C9-C10-C11-C12-C14-C15) rings do not lie in the same
plane and deviate with dihedral angle of 27.34°. The bond length of C6–O1 1.246(6)Å and
S(1)-C(1) 1.682(6)Å is in good agreement with a carbon–oxygen and carbon-sulphur double
bond respectively. The bond length between C9-C10 = 1.398(7)Å is quite close to that
obtained for aromatic ring system whereas, N(3)-C(2) 1.346(7)Å and N(5)-C(7) 1.316(7)
consists well with a carbon–nitrogen double bond. Pertinent bond lengths and angles for
compound PTMPP-THSC are listed in Table 2 and are lying in the reported range.
Figure 2. Molecular structure of compound PropPTMP-ths

1827
ARJUNSINH RANA et al.
Weak force studies reveal that fourteen hydrogen bonds are formed in the molecular
packing of this compound. Six hydrogen bonds are conventional hydrogen bonds whereas
remaining eight bonds are non-conventional hydrogen bonds. The non-conventional
hydrogen bonds involve C-H unit as donor groups, whereas, acceptors are oxygen, nitrogen
and sulphur atoms (Table 3).
Crystal packing of compound PropPTMP-ths involving six intermolecular hydrogen
bonding is as shown in Figure 3 which consists of 18-membered pseudo cavity formed by
hydrogen binding.
Figure 3. Packing of PropPTMP-ths forming cavity
The molecular structure along with the crystallographic numbering scheme of AcPTMP-ths
is depicted in Figure 4. The compound crystallizes in monoclinic crystal system with space
group P21/n. Each unit consists of four molecules of the compouns. The molecule is almost
coplanar and the central pyrazolone ring (N5-N4-C5-C4-C6) slightly deviate from phenyl ring
with dihedral angle of 2.65°. Carbon-oxygen and carbon-sulphur double are found to be
C5–O1 1.249(5)Å and S(1)-C(1) 1.672(5)Å respectively which are in good agreement with the
reported literature values. Carbon–nitrogen double bond N(3)-C(2) 1.341(7)Å and N(5)-C(6)
1.305(5) consists well and the bond length between C14-C13 = 1.382(6)Å is quite close to that
obtained for aromatic ring system. All other bond lengths and angles for compound
AcPTMP-ths are listed in Table 2 and are lying in the reported range.
Figure 4. Molecular structure of compound AcPTMP-ths

Synthesis, Crystal Structural Characterization
1828
Weak force studies reveal the presence of seven hydrogen bonds in the molecular packing
of this compound. Four hydrogen bonds are conventional hydrogen bonds whereas remaining
three bonds are non-conventional hydrogen bonds. The non-conventional hydrogen bonds
involve C-H unit as donor groups, whereas, acceptors are oxygen, nitrogen and atoms (Table 3).
Chemical shift of hydrogen in the IR spectrum, the υ(N-H) spectral region is broad,
showing the existence of N-H-O hydrogen bond. The band for υ(C=O) at 1628 cm-1 is at
lower wave number than that usually found for carbonyls, reflecting the involvement in
hydrogen bonding with NH of the thiosemicarbazone and pyrazol-5-one compound. In
1H NMR N(1) is easily distinguished from that of N(2) because the latter (7.161 ppm)
appears as a doublet due to that the two hydrogen atom on N(2) are nonequivalent because
one of them is involved in hydrogen bonding, which is consistent with the crystal structure
analysis. The single peak at 8.3 ppm is assignable to the N(1)-H. The single of 10.2 ppm is
not a unit because N(5) share the same hydrogen with O on the neighboring molecule.
The x-ray structural investigation of AcPTMP-ths shows that in this compound has a
stair form packing arrangement. An ORTEP plot along with the atom numbering scheme of
AcPTMP-ths is given in Figure 4 and 5. The figure also describes arrangement of the
molecules in the unit cell with intermolecular content through atoms with other atoms of
AcPTMP-ths. The bond lengths and angles for compound AcPTMP-ths are listed in Table 2.
Figure 5. Packing of AcPTMP-ths showing parallel chains linked through hydrogen bonding
Synthesis of Novel 4-acylthiosemicarbazon-2-pyrazoline-5-one
The reaction of 3-methyl-1-(4`-methylphenyl)-2-pyrazoline-5-one (PTMP) with acetyl
chloride or propionyl chloride were carried out under the ordinary condition. The reaction
4-acyl-2-pyrazoline-5-one with thiosemicarbazide produce Schiff base as carried out in
alcohol such as ethanol or methanol at reflux temperature and crystallization by aqueous
alcohol for purification. A yellow prismatic crystal of the titled compounds obtained. The
formation of 4-acylthiosemicarbazon-2-pyrazoline-5-one was confirmed by spectral data viz.
1H NMR, 13C NMR and FTIR.
Antibacterial activity investigation
In the present study, the antibacterial activities of the AcPTMP-ths, PropPTMP-ths and
standard drugs were tested by the agar-cup method in DMF solvent (at concentration of
5000 µg/mL as well as 2500 µg/mL) and were checked against Gram negative bacteria
Escherichia coli MTCC-739), Pseudomonas aeruginosa (MTCC-741), Salmonella typhi (MTCC-

1829
ARJUNSINH RANA et al.
733), Proteus vulgaris (MTCC-1771) and Klebsiella pneumoniae (MTCC-109) and Gram positive
bacteria Staphylococcus aureus (MTCC-96) and Bacillus subtilis (MTCC-619). Table 3 shows
that AcPTMP-ths and PropPTMP-ths compounds have good antibacterial activities against these
bacteria. The results (Table 4) showed that almost all compounds showed nearly better activity. It
is interesting to note that due to the presence of pyrazolone group, these compounds were found to
be efficient antibacterial agents. Use of these ligands system now covers a full of areas ranging
from general consideration of metal-sulphur bonding and electron delocalization in transition
metal complexes to potential biological activity work is under analysis.
Table 3. Antibacterial activities of AcPTMP-ths and PropPTMP-ths with drugs.
Antibacterial activity (Zone size in mm)
Compounds
Gram negative
Gram positive
Bs Sa
Ec
Pa
St
Kp
Pv
AcPTMP-ths
A1=18 A1=17 A1=14 A1=19 A1=12 A1=20 A1=26
A2=14 A2=15 A2=12 A2=16 A2=09 A2=23 A2=22
A3=08 A3=08 A3=08 A3=08 A3=08 A3=08 A3=08
PropPTMP-ths
B1=18 B1=17 B1=17 B1=17 B1=12 B1=13 B1=27
B2=13 B2=13 B2=10 B2=13 B2=09 B2=10 B2=21
B3=08 B3=08 B3=08 B3=08 B3=08 B3=08 B3=08
Ampicillin (20mcg)
Cefotaxim(30mcg)
Gentamicin(10mcg)
Levofloxacin (5mcg) 20
Gatifloxacin (10mcg) 14
Amikacin (30mcg)
Chloramphenicol
(30mcg)
17
23
18
11
13
11
28
25
21
16
16
15
17
18
17
22
16
14
11
23
06
10
20
18
18
18
13
14
19
20
17
08
18
17
18
20
18
16
09
14
19
19
21
19
20
18
20
Ofloxacin (5mcg)
08
24
22
17
16
19
20
Ec-Escherichia coli (MTCC-739),
Pa-Pseudomonas aeruginosa (MTCC-741), St-
Salmonella typhi (MTCC-733), Pv-Proteus vulgaris (MTCC-1771), Kp-Klebsiella
pneumoniae (MTCC-109), Sa-Staphylococcus aureus (MTCC-96) and Bs-Bacillus subtilis
(MTCC-619).
A1, B1, - 5000 µg/mL concentration of respective compound
A2, B2, - 2500 µg/mL concentration of respective compound
A3, B3, – As solvent (DMF) control
Discussion here is restricted only to O, S and N Containing ligands, especially
thiosemicarbazide and its amine substitution like 4-methyl thiosemicarbazide, 4-phenyl
thiosemicarbazide, 4,4-dimethyl thiosemicarbazide and 4,4-diphenyl thiosemicarbazide.
Method
The antibacterial activities of AcPTMP-ths and PropPTMP-ths were studied by standard cup-
plate-agar diffusion method using Mueller-Hinton agar (Himedia, Bombay)25.
The measured quantity of the fresh culture of the respective test organism (0.5 mL) was added
to each heated (nearly < 40 ◦C) agar media tubes. The tubes were shaken well and the
inoculated media were poured in the sterilized petri dishes (10 cm diameter) and then allowed
to set for 30 min. The test solutions of 5000 µg/mL and 2500 µg/mL dilutions of the respective
AcPTMP-ths and PropPTMP-ths (5000 µg/mL and 2500 µg/mL) were prepared in Dimethyl-

Synthesis, Crystal Structural Characterization
1830
formamide (DMF) .The concentrations of tested compounds were decided by MIC (Minimal
Inhibitory concentration) method and selection of test cultures was decided by performing
ditch method. Four cups of 5 mm diameter were cut in the culture media on the petridishes. A
50 micro liter (µL) solution of particular diluted compound (5000 µg/mL or 2500 µg/mL) was
filled with micropipette in the four cups of one of the Petri dishes. All the petri dishes were
allowed to remain in the refrigerator maintained at < 10 ◦C for < 1 h to allow diffusion of the
respective solutions. The petridishes were then transferred to an incubator maintained at < 37 oC
and kept for nearly 24 h. The zones of inhibition appeared were measured with vernier
calipers. The control of DMF showed slight activity. The activities of all compounds are
represented by size of the diameter of zone of inhibition in millimeter.
The antibacterial activity of standard antibiotics was performed by following standard
Kirby-Bayer method (combi-disc method, purchased from Pathoteq Biological Laboratories
(India)). The antibacterial activity of all known antibiotics is represented by size of the
diameter of zone of inhibition in millimeter.
Conclusion
A number of multi-functionalized 4-acylthiosemicarbazone-2-pyrazoline-5-ones were
conveniently prepared by literature method. Investigation of biological activities of this type
of ligands and their metal complexes have identified them as promising potential
antibacterial agent against Gram-positive as well as Gram-negative bacteria. They have
broad-spectrum activity and were found as competitive as marketed known antibiotics drugs.
Acknowledgment
We are grateful to Dahod Anaj Mahajam Sarvajanic Education Society and Principal,
Navajivan Science College, Dahod for the Laboratory facilities, Prof. Hasmukh Modi
Department of Life science, Gujarat University for analysis (biological acivity), Pradeep
Mathur for single crystal x-Ray Powder diffraction analysis done at IIT, powai Mumbai and
Kamlesh Modi (Prima Chemicals) for providing free pyrazolone-5-one intermediate.
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