Chinese Chemical Letters  2013, Vol.24 Issue (12):1045-1048   PDF    
Citation
Kondapalli Venkata Gowri Chandra Sekhar, Thripuraribhatla Venkata Naga Varuna Tara Sasank, Hunsur Nagendra Nagesh, Narva Suresh, Kalaga Mahalakshmi Naidu, Amaroju Suresh.Synthesis of 3,5-diarylisoxazoles under solvent-free conditions using iodobenzene diacetate[J]. Chin. Chem. Lett., 2013,24(12): 1045-1048   
Study of oxidic and sulfided selective hydrodesulfurization catalysts for gasoline using Raman spectroscopy
Kondapalli Venkata Gowri Chandra Sekhara , Thripuraribhatla Venkata Naga Varuna Tara Sasankb, Hunsur Nagendra Nagesha, Narva Suresha, Kalaga Mahalakshmi Naidua, Amaroju Suresha Hui-Feng Lia, Li-Jun Lu a    
* Corresponding authors at:a Department of Chemistry, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Hyderabad 500 078, India;
b Department of Pharmacy, Birla Institute of Technology and Science, Pilani 333 031, India;
c Inner Mongolia Medical College, Hohhot 010059, China
Received:2013-3-28, Revised:2013-6-17, online:2013-12-26.
E-mail addresses:kvgcs@yahoo.com
Abstract:A simple and efficient method has been developed for conversion of chalcone oximes to 3,5-diaryl isoxazoles in excellent yields under solvent-free conditions. The synthesized compounds were characterized by infrared spectroscopy, 1H NMR, 13C NMR and HRMS.
Key words: Isoxazoles     Chalcones     Solid-state synthesis     Iodobenzene diacetate    
1. Introduction

Isoxazoles represent an important class of aromatic hetero- cycles,and are associated with a wide spectrum of biological activities,such as antiviral [1],antimicrobial [2],anti-inflammato- ry [3],anticonvulsant [4],antihyperglycemic [5],anticancer [6] activity,etc.

In general,isoxazoles are obtained by two major routes: [3+2] cycloaddition of alkenes/alkyneswith nitrile oxides,or the reaction of hydroxylamine with a three-carbon atom component [7, 8]. Recently,synthesis of 3,5- and 3,4-disubstituted isoxazoles through transition-metal-catalyzed [3+2] cycloaddition reactions was also reported [9]. To date,a variety of othermethods have also been reported for synthesis of isoxazoles [10].

3,5-Diarylisoxazoles are also synthesized regioselectively by the reaction of chalcones with hydroxylamine hydrochloride using K2CO3 as solid support undermicrowave conditions [11]. However, these methods usually are of limited scope and use harsh conditions. Recently,organic reactions under solvent-free condi- tions have received much attention due to advantages over the conventional methods in terms of time,yields and relatively benign conditions [12]. Presently,there is also a considerable interest in organohypervalent iodine reagents because of their versatile use in solid-state organic reactions [12]. These reagents are used in the synthesis of several heterocyclic compounds in liquid and solid state [13].

In view of the above interest in these compounds and in continuation of our studies on the cyclization of heterocyclic compounds [14] we undertook to develop an efficient and environmentally benign synthesis of 3,5-diarylisoxazoles that proceed under solvent-free conditions. Herein,we report results on the transformation of various substituted chalcone oximes to 3,5-diarylisoxazoles (Scheme 1) with iodobenzene diacetate that leads to the expeditious formation of the title compounds in very good yields. Chalcone oximes are prepared as per the literature protocol [10f, g]. To the best of our knowledge,there is no report on the synthesis of 3,5-diarylisoxazoles under solvent free conditions.

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Scheme 1. Synthesis of 3,5-diarylisoxazoles (2a-q).
2. Experimental

All startingmaterialswere purified by standardmethods before use. All yields refer to isolated products after purification. Melting points were determined in open capillaries using Bü chi 530 melting point apparatus without correction. The reactions were monitored and the purity of the compounds checked by ascending thin layer chromatography (TLC) on silica gel coated aluminium plates (Merck 60 F254,0.25 mm) using mixture of chloroform and methanol. The developed plates were visualized under ultra violet light at 254 and 366 nm. Infrared (IR) spectra were recorded as KBr discs on a Schimadzu IR Prestige-21 FT-IR spectrophotometer (cm-1). 1H NMR spectra were recorded on a Bruker DRX400 spectrometer using tetramethylsilane as internal standard,chemi- cal shifts in ppm. Mass spectra were recorded on a VG-70-S mass spectrometer.

General procedure for synthesis of 3,5-diarylisoxazoles (2 a-q):A mixture of chalcone oxime (1 mmol) and iodobenzene diacetate (1.2 mmol) was ground thoroughly in a pestle andmortar. After 2- 3 min,an exothermic reaction ensued while in some cases slightly warming to ~40℃ for 2 min was required to initiate the reaction. The residue was washed with hexane and then recrystallized,or filtered through a small pad of silica gel,to afford analytically pure products. All the known compounds were identified by comparison of their melting points, 1H NMR,13C NMR data with the literature data.

5-(4-Chlorophenyl)-3-(4-nitrophenyl) isoxazole (2e): 1H NMR (400 MHz,CDCl3):δ 7.98-8.07 (m,4H),7.48-7.53 (m,4H),6.81 (s, 1H);13 CNMR (100 MHz,CDCl3): d 169.8,162.3,151.2,139.1,134.3, 129.3,128.9,128.6,127.8,124.3,99.7. HRMS calcd. for C15H9ClN2O3: 300.0302,found: 300.0301. IR (KBr,cm-1 ):υ 813 and 828 (OOP para substituent),1618 (C=N).

3-(4-Chlorophenyl)-5-(3-nitrophenyl) isoxazole (2i): 1 H NMR (400 MHz,CDCl3): δ 8.68-7.89 (m,4H),7.78-7.46 (m,4H),6.67 (s,1H); 13 C NMR (100 MHz,CDCl3): δ 168.4,162.6,145.2,133.5, 131.6,130.6,129.8,128.9,127.8,124.3,123.5,122.7,96.5. HRMS calcd. for C15H9ClN2O3 300.0302,found 300.0299. IR (KBr,cm-1 ):υ 816,782 and 703 (OOP para substituent),1611 (C=N).

5-(2,6-Dichlorophenyl)-3-(4-methylphenyl) isoxazole (2m): 1H NMR (400 MHz,CDCl3):δ 8.52-8.54 (d,2H),7.88-7.84 (s,1H), 7.63-7.61 (d,2H),7.48-7.46 (d,2H),6.92 (s,1H),2.6 (s,3H); 13 C NMR (100 MHz,CDCl3):δ 170.9,168.1,151.4,146.3,140.3,132.7, 130.2,129.1,128.8,126.9,124.5,115.6,94.5,22.9. HRMS calcd. for C16H11Cl2NO304.1706,found 304.1729. IR (KBr,cm-1 ): υ 823 (OOP para substituent),1623 (C=N).

5-(2,3-Dichlorophenyl)-3-(4-methylphenyl) isoxazole (2n): 1 H NMR (400 MHz,CDCl3): δ 8.61-8.67 (m,1H),7.82-7.78 (m,1H), 7.76 (m,1H),7.58-7.56 (d,2H),7.39-7.37 (d,2H),6.83 (s,1H),2.3 (s,3H); 13 C NMR (100 MHz,CDCl3): δ 169.8,164.2,149.4,138.3, 132.1,129.6,125.2,121.3,119.8,116.3,115.5,113.2,98.7,24.3. HRMS calcd. for C16H11Cl2NO: 304.1706,found: 304.1711. IR (KBr, cm1 ): υ 799 (OOP para substituent),1629 (C=N).

5-(2,4-Dichlorophenyl)-3-(4-methylphenyl) isoxazole (2o): 1 H NMR (400 MHz,CDCl3): δ8.72-8.69 (s,1H),8.02-8.05 (d,1H), 7.87-7.89 (d,1H),7.57-7.59 (d,2H),7.48-7.51 (d,2H),6.97 (s,1H), 2.37 (s,3H); 13 C NMR (100 MHz,CDCl3): δ 167.4,165.2,148.7, 135.3,131.8,129.1,127.6,126.5,125.7,122.5,121.2,115.3,96.5, 25.3. HRMS calcd. for C16H11Cl2NO: 304.1706,found: 304.1734. IR (KBr,cm-1 ): υ 806 (OOP para substituent),1627 (C=N).

5-(2,4-Dichlorophenyl)-3-(2-methoxyphenyl) isoxazole (2p): 1 H NMR (400 MHz,CDCl3): δ 8.57-8.52 (s,1H),7.93-7.98 (d,1H), 7.61-7.68 (d,1H),7.26-7.29 (m,2H),7.15-7.18 (m,1H),7.05-7.08 (m,1H),6.81 (s,1H),3.42 (s,3H); 13 C NMR (100 MHz,CDCl3): δ 169.1,165.8,150.7,142.6,138.3,133.3,130.1,129.3,127.9,126.8, 125.7,123.5,121.2,118.3,94.1,57.3. HRMS calcd. for C16H11Cl2NO2: 300.0302,found: 300.0299. IR (KBr,cm-1 ): υ763 (OOP ortho substituent),1123 & 1186 (C-O),1621 (C5=N).

5-(2,3-Dichlorophenyl)-3-(2-methoxyphenyl) isoxazole (2q): 1 H NMR (400 MHz,CDCl3): δ 8.62-8.65 (m,1H),8.12-8.17 (m,1H), 7.83-7.87 (m,1H),7.32-7.35 (m,2H),7.19-7.23 (m,1H),7.02-7.07 (m,1H),6.76 (s,1H),3.36 (s,3H); 13 C NMR (100 MHz,CDCl3): δ 168.8,164.1,149.7,139.3,136.2,132.6,129.4,128.9,127.7,126.3, 125.7,123.3,122.7,119.3,95.2,53.7. HRMS calcd. for C16H11Cl2NO2: 300.0302,found: 300.0299. IR (KBr,cm-1 ):υ779 (OOP ortho substituent),1082 & 1167 (C-O),1619 (C=N).

3. Results and discussion

This conversion simply involves a thorough mixing of substrates with iodobenzene diacetate at room temperature (slightly warming in some cases) via an exothermic reaction. Chalcone oximes forma yellowish eutecticmelt with iodobenzene diacetate upon mixing prior to the occurrence of a mildly exothermic reaction. This is in accordance with the postulated model for such solid-solid reactions [14b, 15].

The IR spectrum of compound 2e showed an absorption at υmax = 827-832 cm-1 (aromatic C-H OOP bending {para}),1344 and 1510 cm-1 (aromatic nitro),1618 cm-1 (C=N stretch). In the 1 H NMR spectrum,the only proton of the isoxazole nucleus resonated as a sharp singlet at δ 6.81 and the aromatic protons were seen as a multiplet at δ 7.48-8.07. In the 13 C NMR,signals appeared at δ 169.8,162.3,151.2,139.1,134.3,129.3,128.9,128.6, 127.8,124.3,99.7. The high resolution mass spectra of this compound exhibited the molecular ion peak at m/z 300.0301 which is in agreement with the calculated value 300.0302.

Under optimized conditions,syntheses of 3,5-diarylisoxazoles, 2a-q,were undertaken. All the melting points of synthesized compounds (Table 1) were in agreement with the melting points found in the literature [16]. The plausible mechanism for the formation of the product is outlined in Scheme 2.

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Scheme 2.. The plausible mechanism for the formation of the product.

Table 1
Physical properties of 3,5-diarylisoxazoles (2a-q).
4. Conclution

In conclusion,we have developed a simple,benign and expeditious synthesis of biologically significant 3,5-diarylisoxa-zoles in good yields under solvent-free conditions and fully characterized the products.

5. Acknowledgments

The financial assistance provided by DST (under Fast Track scheme: SR/FT/CS-076/2009),New Delhi,India is gratefully acknowledged. Authors are thankful to SAIF,CDRI,Lucknow,India and the SAIF,Punjab University,Chandigarh,India for analytical and spectral data.

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