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Journal of Chemistry and Chemical Sciences, Vol.

5(7), 351-356, July 2015 ISSN 2229-760X (Print)


(An International Research Journal), www.chemistry-journal.org ISSN 2319-7625 (Online)

Synthesis Of Novel Pyrazole Derivatives Of Chalcones


Mustaqeem Mohammed A* and Juliet Miranda

Organic Research Laboratory, Department of Chemistry,


Royal College, Penkar Pada, Mira Road, Thane, Maharashtra, INDIA.
email: mustaqeem19@gmail.com and jpd_feb@redifmail.com

(Received on: July 7, 2015)

ABSTRACT

Numbers of chalcones were synthesized by reacting different substituted


aldehyde and acetophenone OR 2-acetyl thiophene prepared by claisen-schmidt
condensation reaction in NaOH solution in ethanol. Chalcones were reacted with
hydrazine hydrate to obtained pyrazole moiety. The synthesized heterocyclic were
characterized on the basis of physical, chemical tests and spectroscopic data and
were tested in vitro for the anti bacterial and anti fungal activity using cup plate
method using nutrient agar media. Evaluation of the compounds revealed
remarkable antibacterial and antifungal activity observed.
Keywords: 2-[2-(4-Chloro-phenyl)-acetyl]-benzoic acid, Acetophenone,
1-Thiophen-2-yl-ethanone, Hydrazine hydrate, pyrazole.

INTRODUCTION
Chalcones either natural or synthetic are known to exhibit various biological
activities. Chalcones were prepared by condensation of acetophenone with aromatic
aldehydes in presence of suitable condensing agent1,2. They undergo a variety of chemical
reactions that leads to many heterocyclic compounds3-6. Chalcones have been used as
intermediates for the preparation of compounds having therapeutic value7,8. Many reviews
reveal that chalcone derivatives exhibit diverse pharmacological activities, such as potential
Cytotoxic agents, antimicrobial agents, antiviral, anti-inflammatory, anesthetic, etc.9,10. In the
view of the varied biological and pharmacological applications, we have planned to
synthesize some heterocyclic derivatives of chalcone and test their antibacterial activity.
Whereas pyrazole is a class of organic compounds, which has many applications in different
field. One of the methods for the synthesis of such compound is from α, β-unsaturated
carbonyl by the cyclization with substituted hydrazines.
EXPERIMENTAL
Melting points of all synthesized compounds were determined in open capillary

July, 2015 | Journal of Chemistry and Chemical Sciences | www.chemistry-journal.org


352 Juliet Miranda, et al., J. Chem. & Cheml. Sci. Vol.5 (7), 351-356 (2015)
tubes on an electro thermal apparatus and are uncorrected. The progress of reaction was
monitored by thin layer chromatography on silica gel coated aluminum plates (Merck) as
adsorbent and UV light as visualizing agent. 1H NMR spectra were recorded on Varian 500
MHz NMR spectrophotometer using CDCl3/DMSO-d6 as solvent and TMS as an internal
standard (chemical shifts in δ ppm). C, H, N estimation was recorded on Carlo Erba 1108
(CHN) Elemental Analyzer.

METHODS

Synthesis of 2-[2-(4-Chloro-phenyl)-acetyl]-benzoic acid hydrazide (2)


Compound (1) (2.37 gm, 0.01 mole) and SOCl2 (2.17gm 0.03 mole), MDC in 100
mL round bottom flask were stirred for 30 min at room temperature to obtained acid chloride
of compound (1). Excess of reagent and solvents were distilled off.
Acid chloride and excess of hydrazine hydrate in dry methanol were transferred in
100 mL round bottom flask and refluxed for 4-5mins. After completion of the reaction
(monitored by TLC), the reaction mixture was cooled, poured on crushed ice, on
neutralization of the contents with sodium bicarbonate solution (20%) a solid mass separated
out, which was filtered, washed with water, dried and recrystallised from methanol to get (2).
(Yield 75 %, m.p. 224-226°C).
IR (cm-1): v 3350-3380 (NH-NH2), 1680 (C=O), 1630 (NH-NH2), 1600-1480(aromatic ring),
730-830 (disubstituted aromatic ring).
1
H NMR (500 MHz, DMSO-d6, ppm): 2.03 (s, 2H, NH2), 3.82 (s, 2H, CH2), 7.00 – 8.08 (m,
8H, ArH), 9.09 (s, 1H, NH).
Synthesis of 3-(substituted)phenyl-1-thiophen-2-yl-propenone (3a-d)
Benzaldehyde derivative (0.01 mol) and 1-Thiophen-2-yl-ethanone (0.01 mol) were
dissolved in ethanol (25 mL).Sodium hydroxide solution, 10% (25 mL) was added slowly
and the mixture stirred for 4 hrs then it was poured into 400 mL of water with constant
stirring and left overnight in Refrigerator. The precipitate obtained was filtered, washed and
recrystallized from ethanol.
Synthesis of 1-phenyl-3-(substituted)phenylpropenone (4a-d):
Benzaldehyde derivative (0.01 mol) and acetophenone (0.01 mol) were dissolved in
ethanol (25mL).Sodium hydroxide solution, 10% (25 mL) was added slowly and the mixture
stirred for 4 hrs then it was poured into 400 mL of water with constant stirring and left
overnight in Refrigerator. The precipitate obtained was filtered, washed and recrystallized
from ethanol.
Synthesis of pyrazolines derivatives
A mixture of compound (2) (0.0015 mol), chalcones (3&4) (0.001 mol) and sodium
hydroxide (0.001 mol) in (25 ml) ethanol was refluxed with stirring about (1-2 hrs.) until

July, 2015 | Journal of Chemistry and Chemical Sciences | www.chemistry-journal.org


Juliet Miranda, et al., J. Chem. & Cheml. Sci. Vol.5 (7), 351-356 (2015) 353
complete the reaction which was monitored by TLC and the formation of ppt. of the
pyrazoline products (5&6). The ppt. was isolated by suction filtration, washed with ethanol
and water to neutralize, dried and purified by recrystallization from ethanol. The physical
properties of the prepared pyrazolines (5&6) were summarized in table (1).
Table (1): Some physical properties for the prepared pyrazolines (5&6)
Compound R Molecular Molecular Melting Yield Colours
Formula weight point (°C) (%)
5a 4-Cl C28H20Cl2N2O2S 518 110-112 75 White
5b 2-OH C28H21ClN2O3S 500.5 114-116 74 Yellow
5c 4-CH3 C29H23ClN2O2S 498.5 115-116 76 Cream yellow
6a 4-Cl C30H22Cl2N2O2 512 180-182 72 Light yellow
6b 4-OH C30H23ClN2O3 494.5 186-188 71 Yellow
6c H C30H23ClN2O2 478.5 178-180 72 White
6d 3-NO2 C30H22ClN3O4 523.5 200-202 73 Light green
*Satisfactory C, H and N analysis were obtained for all the compounds.

SPECTRAL INTERPRETATION
2-(4-Chloro-phenyl)-1-{2-[3-(4-hydroxy-phenyl)-5-thiophen-2-yl-4,5-dihydro-pyrazole-
1-carbonyl]-phenyl}-ethanone 5b
IR (cm-1): v (OH) 3384; v (CH) 2984; v (C=O) 1705; v (C=O) 1675; v (N-N=C) 1238.
1H NMR d (ppm): 2. 0 (d, 2H, CH2); 3.80 (s, 2H, CH2); 4.9 (t, 1H, CH); 5.2 (s, 1H, OH);
7.05- 8.3 (m, 15H, Ar-H);
13 C NMR d ppm: 38.25 (CH2); 42.23 (CH2); 40.32 (CH2); 122-149 (Ar-C); 156-158
(-C=N,); 168.4 (C=O); 196.4 (C=O); MS: 500.5 (M+)
2-(4-Chloro-phenyl)-1-[2-(5-thiophen-2-yl-3-p-tolyl-4,5-dihydro-pyrazole-1-carbonyl)-
phenyl]-ethanone 5c
IR (cm-1): v (CH) 2980; v (C=O) 1700; v (C=O) 1680; v (N-N=C) 1231.
1H NMR d (ppm): 1.9 (s, 3H, CH3); 2. 0 (d, 2H, CH2); 3.80 (s, 2H, CH2);4.9 (t, 1H, CH);
7.05- 8.3 (m, 15H, Ar-H);
13 C NMR d ppm: 22.25 (CH3); 37.28 (CH2); 43.21 (CH2); 40.32 (CH2); 123-148 (Ar-C);
156-158 (-C=N,); 168.8 (C=O); 195.5 (C=O); MS: 498.5 (M+)
2-(4-Chloro-phenyl)-1-{2-[3-(4-chloro-phenyl)-5-phenyl-4,5-dihydro-pyrazole-1-
carbonyl]-phenyl}-ethanone 6a:
IR (cm-1): v (CH) 2980; v (C=O) 1700; v (C=O) 1680; v (N-N=C) 1231.
1H NMR d (ppm): 2. 1 (d, 2H, CH2); 3.85 (s, 2H, CH2);4.8 (t, 1H, CH); 7.05- 7.6 (m, 15H,
Ar-H);
13 C NMR d ppm: 38.28 (CH2); 42.21 (CH2); 40.72 (CH2); 118-145 (Ar-C); 156-158
(-C=N,); 168.8 (C=O); 195.5 (C=O); MS: 512 (M+)

July, 2015 | Journal of Chemistry and Chemical Sciences | www.chemistry-journal.org


354 Juliet Miranda, et al., J. Chem. & Cheml. Sci. Vol.5 (7), 351-356 (2015)
2-(4-Chloro-phenyl)-1-{2-[3-(4-hydroxy-phenyl)-3-phenyl-4,5-dihydro-pyrazole-1-
carbonyl]-phenyl}-ethanone 6b:
IR (cm-1): v (OH) 3330, v (CH) 2990; v (C=O) 1678; v (C=O) 1720, v (aromatic ring)
1630-1410; v (C-N) 1185;
IR (cm-1): v (CH) 2985; v (C=O) 1710; v (C=O) 1685; v (N-N=C) 1241.
1H NMR d (ppm): 2.1 (d, 2H, CH2); 3.82 (s, 2H, CH2);4.8 (t, 1H, CH); 5.5 (s, 1H, OH);
7.05- 7.7 (m, 15H, Ar-H);
13 C NMR d ppm: 37.28 (CH2); 43.21 (CH2); 40.32 (CH2); 120-149 (Ar-C); 155-158
(-C=N,); 169.7 (C=O); 196.5 (C=O);MS: 494.5 (M+)
Reaction Scheme
O O

OH
NHNH2
O
1) SOCl2 / MDC stirr RT O

2) NH2NH2.H2O / CH3OH

Cl
(2) Cl
(1)

O
H
C CH
S R HC CH
O R

(3) (4)

R N N R
S N N

O
O
O
O

Cl
Cl (6)
(5)

Antimicrobial and antifungal activities


All the newly synthesized pyrazoles derivative were evaluated for their antibacterial
activity against Gram-negative bacteria, E. coli and P.putide, Gram-positive bacteria,

July, 2015 | Journal of Chemistry and Chemical Sciences | www.chemistry-journal.org


Juliet Miranda, et al., J. Chem. & Cheml. Sci. Vol.5 (7), 351-356 (2015) 355
B.subtilis, and S.lactis, Fungi A.niger and P.Sp.& Yeast C.albicans using disc diffusion
method. The zone of inhibition was measured in mm and the activity was compared with
standard drug. The results of antibacterial screening studies are reported in Table-2.

Table-2: Antibacterial in vitro activity of compounds 3a-g

Inhibition Zone (mm) *

Compds Gram-negative Gram-positive Fungi Yeast

E.coli P.putide B.subtilis S.lactis A.niger P.Sp. C.albicans

5a 17 16 16 18 15 17 10

5b 15 14 17 18 16 12 11

5c 16 18 19 19 17 9 10

6a 17 16 18 17 19 10 9

6b 14 16 17 20 16 9 9

6c 16 17 16 20 18 11 10

6d 14 14 17 21 15 12 10

DMSO 0 0 0 0 0 0 0

Ampicilin® 24 20 19 22 24 14 14
E.coli. = Escherichia coli; P.putide = Pseudomonas Putide; B. subtilis = Bacillus Subtilis; S.
lactis = Sterptococcus lactis; A. niger = Aspergillus niger; P. Sp. = Penicillium Sp; C. albicans =
candida Albicans.
The sensitivity of microorganisms to the tested compounds is identified in the following manner*;
Highly Sensitive = Inhibition zone: 15-20 mm
Moderately Sensitive = Inhibition zone: 10-15 mm
Slightly Sensitive = Inhibition zone: 5-10 mm
Not Sensitive = Inhibition zone: 0 mm
* Each result represents the average of triplicate readings.
* N.B. Concentration selected was 100 µg/ml and DMSO was used as the solvent.

CONCLUSION
The synthesized pyrazolines 5a-c & 6a-d all are novel. Compounds with electron
releasing groups such as hydroxyl, methoxy and compounds having pharmacophores such as
chloro groups and all these groups are present in moiety exhibited good antimicrobial
activity. The synthesized compounds 5a-c & 6a-d showed convincing activity against Fungi,

July, 2015 | Journal of Chemistry and Chemical Sciences | www.chemistry-journal.org


356 Juliet Miranda, et al., J. Chem. & Cheml. Sci. Vol.5 (7), 351-356 (2015)
Yeast, Gram positive and Gram negative organisms. The data reported in this article may be
helpful guide for the medical chemists who are working in this area.

ACKNOWLEDGEMENT

Authors are thankful to the Principal A. E. Lakdawala and Management of Royal


College, Mira Road, Thane for constant encouragement and providing necessary facilities.
Authors are also thankful to, The Director, TIFR Mumbai for spectral data.

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