Synthesis and characterization of novel 1-chloroacetyl derivatives of 2-pyrazolines

Article abstract of DOI:10.1515/HC.2011.013

Five novel acetyl derivatives of 2-pyrazoline 6-10 were synthesized by the reaction of chalcones 1-5 with hydrazine hydrate and chloroacetic acid in ethanol. The products were purified by silica gel chromatography and characterized by ESI-MS, FT-IR, UV, <

Full text of DOI:10.1515/HC.2011.013

Heterocycl. Commun., Vol. 17(1-2), pp. 61–63, 2011 • Copyright © by Walter de Gruyter • Berlin • Boston. DOI 10.1515/HC.2011.013
Synthesis and characterization of novel 1-chloroacetyl
derivatives of 2-pyrazolines
of the products were elucidated by UV, IR, ESI-MS, 1H NMR,
Pramod Singh, Jagmohan S. Negi, Geeta Joshi
Nee Pant* and Mohan S.M. Rawat
13C NMR and DEPT spectral methods. For example, the IR
spectra of compounds 6– 10 show a strong band at 1675–
Department of Chemistry, HNB Garhwal University,
Srinagar Garhwal-246174, Uttarakhand, India
1660 cm-1 for a carbonyl group. The bands at 1590–1440 cm-1
for C=N and 1090–1056 cm-1 for C-N moieties are also pres-
ent. The electronic spectra of 2-pyrazoline in the UV region
in methanol show three absorption bands in the regions of
318–291, 285–255 and 242–232 nm assignable to the respec-
*Corresponding author
e-mail: geeta_joshi4f54@rediffmail.com
1
tive n-π*, π-π* and n-σ* transitions. The H NMR and 13C
Abstract
NMR spectra of compounds 6– 10 are also highly informative.
In summary, a series of 2-pyrazolines bearing chloroacetyl
group at the N-1 atom were synthesized and characterized.
Biological assays of these compounds are under study.
Five novel acetyl derivatives of 2-pyrazoline 6–10 were syn-
thesized by the reaction of chalcones 1–5 with hydrazine
hydrate and chloroacetic acid in ethanol. The products were
purified by silica gel chromatography and characterized by
ESI-MS, FT-IR, UV, 1H NMR, 13C NMR and microanalysis.
Experimental
Melting points were determined in open capillary on a Metzer ap-
paratus and are uncorrected. The IR spectra were recorded in KBr
pellets on a Perkin Elmer FT-IR-RX-01 spectrophotometer. The UV
spectra were recorded on a λ-25 Perkin Elmer UV-Visible spectro-
Keywords: chalcones; chloroacetic acid; chromatography;
hydrazine hydrate; pyrazolines.
1
photometer in chloroform. The H and 13C NMR spectra were ob-
Introduction
tained in CDCl3 at 300 MHz and 75 MHz, respectively, on a Brucker
DPX spectrometer using TMS as the reference. Chalcones 1–5 were
prepared as reported previously (Rojas et al., 2002).
Pyrazoline derivatives are antiangiogenic (Abadi et al., 2003),
antifungal (Dawane et al., 2010), antidepressant (Rajendra et
al., 2005), immunosuppressive (Lombardino and Otterness,
1981), anticonvulsant (Ozdemir et al., 2007), antitumor (Congiu
et al., 2010), antiamoebic (Budakoti et al., 2006), antibacterial
(Zitouni et al., 2005), antimycotic (Nauduri and Reddy, 1998),
anti-inflammatory (Sharma et al., 2010), antiproliferative
(Kostakis et al., 2002) and antiviral (Manfredini et al., 1992),
agents. Pyrazolines have also been used extensively as use-
ful synthons in organic synthesis (Azarifar and Ghasemnejad,
2003). The reaction of chalcones and related α,β-unsaturated
ketones with hydrazine hydrate has been investigated under
various conditions (Mishriky et al., 1996; Pant et al., 2011).
Similar derivatives have also been synthesized by the reaction
of chromones with hydrazines (Sammour, 1964). The reaction
of exocyclic α,β-unsaturated ketones with diphenylmethane
has provided spiro-1-pyrazolines as stable products (Toth et
al., 1993; Neudeck, 1996; Levai et al., 2004). Carboxylic acid
derivatives of 2-pyrazolines have been synthesized by Levai
and Jeko (2007). The present paper deals with the synthesis of
novel 2-pyrazolines (Scheme 1) by the reaction of chalcones
with hydrazine hydrate in the presence of chloroacetic acid.
General method for the synthesis of 2-pyrazolines 6–10
A mixture of chalcone 1–5 (15 mmol) and chloroacetic acid
(15 mmol) was treated dropwise with a solution of hydrazine hydrate
(30 mmol) in ethanol (15 ml). The mixture was heated under reflux
for 24 h with constant stirring. Then the resultant solution was cooled
and poured onto crushed ice. The product 6–10 was separated by
either column or radial chromatography on silica gel eluting with
hexane/ethyl acetate (95:5). The fractions were visualized by TLC
on Kieselgel 60 F254 layer using the same eluent.
1-Chloroacetyl-3,5-diphenyl-2-pyrazoline (6) Pale yellow crystals
from ethyl acetate; yield 62%; mp 125–130°C; UV/VIS: λmax 305, 275,
238 nm; IR: ν 1660, 1443, 1142, 750 cm-1. 1H NMR: δ 3.21 (dd, 1H),
3.78 (dd, 1H), 4.64 (s, 2H), 5.56 (dd, 1H), 7.81-7.21 (m, 10H); 13C
NMR: δ 164.1, 155.6, 148.7, 131.0-125.8, 60.6, 42.4; ESI-MS: m/z 299
(M+H)+, 321 (M+Na)+, 337 (M+K)+. Anal. Calcd. for C17H15N2OCl:
C, 68.34; H, 5.02; N, 9.38. Found: C, 68.31; H, 5.00; N, 9.35.
1-Chloroacetyl-5-(4-chlorophenyl)-3-phenyl-2-pyrazoline
(7) Pale yellow crystals from ethyl acetate; yield 52%; mp 191–
193°C; UV/VIS: λmax 291, 255, 235 nm; IR: ν 1668, 1486, 1169,
1
552, 3315 cm-1; H NMR: δ 3.28 (dd, 1H), 3.81 (dd, 1H), 4.68 (s,
2H), 5.58 (dd, 1H), 7.82-7.21 (m, 9H); 13C NMR: δ 160.1, 155.6,
148.6, 130.9-123.9, 60.5, 42.3; ESI-MS: m/z 333 (M+H)+, 355
(M+Na)+, 371 (M+K)+. Anal. Calcd. for C17H14N2OCl2: C, 61.26;
H, 4.20; N, 8.40. Found: C, 61.24; H, 4.17; N, 8.38.
Results and discussion
Reaction of chalcones, hydrazine hydrate and chloroacetic acid
afforded 2-pyrazolines 6– 10 in moderate yields. The structures
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62 P. Singh et al.
O
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Acknowledgements
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Received April 23, 2011; accepted May 16, 2011
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