Chinese Chemical Letters  2014, Vol.25 Issue (01):146-148   PDF    
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Poovan Shanmugavelan, Murugan Sathishkumar, Sangaraiah Nagarajan, Alagusundaram Ponnuswamy.An efficient and facile synthesis of novel 1,2,3-triazolyl-N-acylpyrazoline hybrids[J]. Chin. Chem. Lett., 2014,25(01): 146-148   
An efficient and facile synthesis of novel 1,2,3-triazolyl-N-acylpyrazoline hybrids
Poovan Shanmugavelan, Murugan Sathishkumar, Sangaraiah Nagarajan, Alagusundaram Ponnuswamy     
* Corresponding authors at:Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625021, India
Received:2013-6-9, Revised:2013-9-22, online:2013-11-8.
E-mail addresses:ramradkrish@yahoo.co.in
Abstract: An efficient and facile synthesis of a library of hitherto novel 1,2,3-triazolyl-N-acetyl/N-propionylpyrazoline hybrids (16 examples) in excellent yields (90%-96%) has been accomplished from easily accessible 1,2,3-triazolyl chalcone precursors.
Key words: Facile     Efficient     1,2,3-Triazole     Pyrazolines     Hybrids     1,2,3-Triazolyl-N-acylpyrazolines    
1. Introduction

Recently, considerable attention has been focused on pyrazolines and substituted pyrazolines due to their interesting biological activities. They possess anti-microbial [1], anti-fungal [2], antidepressant [3], anti-convulsant [4], anti-inflammatory [5], etc. properties. Moreover, N-acetyl pyrazoline derivatives exhibit important pharmaceutical profiles [6, 7, 8]. Hence, the pyrazoline framework represents an interesting template for combinatorial [9] as well as medicinal chemistry [10, 11]. On the other hand, 1,2,3-triazoles have received much attention due to their interesting bioactivity profile such as anti-biotic, anti-fungal [12], anti-cancer [13], anti-HIV [14], anti-microbial [15], etc. properties. Also, they serve as potential chemotherapeutic agents for various diseases [16].

In connection with the above and in continuation of our earlier work on environmentally benign, green synthesis of 1,2,3-triazolyl chalcone hybrids [17], we decided to attempt the synthesis of molecules containing both of the two pharmacologically active moieties mentioned above in a single frame. Thus, we disclose the synthesis of 1,2,3-triazolyl-N-acylpyrazoline hybrids from easily accessible 1,2,3-triazolyl chalcones, the details of which are presented vide infra.

Chalcones, belonging to the flavonoids family, are convenient synthons for the synthesis of five [18], six [19] and seven membered [20] heterocyclic compounds. With regard to pyrazoline derivatives, several methods have been employed for their synthesis, including the condensation of chalcones with hydrazine, hydrazine derivatives [21, 22, 23, 24] and thiosemicarbazide [25] under acidic [21, 22] or basic [25] conditions, and the cycloaddition of nitrilimines, generated in situ from the corresponding hydrazonoyl halides by the action of a suitable base, to carbon-carbon double bonds of a dipolarophile [26, 27, 28, 29]. Hence, considerable interest has been focused on the synthesis of pyrazolines from chalcones.

2. Experimental

Typical procedure: To a solution of (E)-1-(1-benzyl-5-methyl- 1H-1,2,3-triazol-4-yl)-3-(4-methylphenyl)prop-2-en-1-one [18] (1e, 1.0 equiv.) and hydrazine hydrate (2.0 equiv.) in acetic acid (5 mL) was refluxed for 3 h. Then, the reaction mixture was poured onto ice-water to afford the 1,2,3-triazolyl-N-acetylpyrazoline hybrid (2e) in 96% yield as a white solid, which was filtered and recrystallized from ethanol.

1-(3-(1-Benzyl-5-methyl-1H-1,2,3-triazol-4-yl)-5-(4-methylphenyl)- 4,5-dihydro-1H-pyrazol-1-yl)ethanone (2e): Mp: 150- 151 ℃; 1H NMR (300 MHz, CDCl3): δ 7.11-7.37 (m, 9H, ArH), 5.54 (s, 2H, NCH2), 5.50 (dd, 1H, J = 4.8 & 12.0 Hz, CH), 3.87(dd, 1H, J = 12.0 & 18.6 Hz, CH2), 3.44 (dd, 1H, J = 4.8 & 18.6 Hz, CH2), 2.51(s, 3H, COCH3), 2.32 (s, 3H, CH3), 2.29 (s, 3H, ArCH3); 13C NMR (75 MHz, CDCl3): δ 168.46, 149.47, 138.68, 138.24, 137.19, 134.25, 132.80, 129.41, 129.08, 128.53, 127.25, 125.65, 58.69, 51.95, 43.25, 21.79, 21.00, 9.41; Mass (ES/MS): m/z 396.58 [M+Na]+; Anal. Calcd. for C22H23N5O: C 70.76, H 6.21, N 18.75. Found: C 70.70, H 6.22, N 18.78.

3. Results and discussion

Perusal of literature indicates a lack of reports on the synthesis of N-acylpyrazolines linked with a 1,2,3-triazole core. In this regard, we herein report synthesis of novel 1,2,3-triazolyl-Nacylpyrazoline hybrids in a facile and efficient manner starting from chalcones [17].

For the purpose of optimization, synthesis of N-acetylpyrazoline (3a) was attempted (Scheme 1) under different conditions viz. (i) reaction through conventional heating (ii) reaction under microwave irradiation. The details are presented below.

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Scheme 1.Optimization for the synthesis of 1,2,3-triazole-N-acetylpyrzoline hybrid (3a).
A mixture of 1,2,3-triazolyl chalcone (1a, 1.0 equiv.) and hydrazine hydrate (2.0 equiv.) in acetic acid was conventionally heated to reflux. It was noted that the yield of N-acetylpyrazoline (2a) was increased and reached 95% in three hours. However, by changing the source of heating to microwave irradiation, a comparable yield of the product could not be obtained (Table 1). Thus, conventional heating was found to be the best methodology for the target compounds.

Table 1
Optimization for the synthesis of 1,2,3-triazole-N-acetylpyrzoline hybrid (3a).
Following optimization, the broad scope of the present protocol was established via the synthesis of a library of novel 1,2,3- triazolyl-N-acetyl/N-propionylpyrazoline hybrids (2a-p, Scheme 2) in excellent yields (90%-96%, Table 2), and it was noted that the reaction involving acids with long alkyl chains such as butyric acid, pentanoic acid, etc. was not satisfactory.

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Scheme 2.Synthesis of 1,2,3-triazolyl-N-acetyl/N-propionylpyrzolines (2).

Table 2
Synthesis of 1,2,3-triazolyl-N-acetyl/N-propionylpyrazoline hybrids (2a–p).
All the synthesized compounds were completely characterized by IR, NMR (1D & 2D) and mass spectral techniques. The feasible mechanism is presented vide Scheme 3.

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Scheme 3.A feasible mechanism for N-acylatedpyrazolines.
4. Conclusion

In conclusion, we have achieved an efficient and facile synthesis of a library of hitherto novel 1,2,3-triazolyl-N-acetyl/N-propionylpyrazoline hybrids in excellent yields via easily accessible chalcones.

Acknowledgments

The authors wish to thank IRHPA, DST for providing 300 MHz NMR facility and UGC (BSR)-India for giving financial support as JRF & SRF.

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