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Synlett 2006(11): 1765-1767  
DOI: 10.1055/s-2006-944200
LETTER
© Georg Thieme Verlag Stuttgart · New York

A Novel, One-Pot, Three-Component Synthesis of 1,2,4-Oxadiazoles under Microwave Irradiation and Solvent-Free Conditions

Mehdi Adib*a, Mohammad Mahdavia, Niusha Mahmoodia, Hooshang Pirelahia, Hamid Reza Bijanzadehb
a School of Chemistry, University College of Science, University of Tehran, Tehran, Iran
Fax: +98(21)66495291; e-Mail: madib@khayam.ut.ac.ir;
b Department of Chemistry, Tarbiat Modarres University, Tehran, Iran
Further Information

Publication History

Received 19 February 2006
Publication Date:
04 July 2006 (online)

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Abstract

A novel synthesis of 3,5-disubstituted 1,2,4-oxadiazoles is described from a one-pot, three-component reaction between ­nitriles, hydroxylamine, and Meldrum’s acids under microwave ­irradiation and solvent-free conditions in good to excellent yields.

Key words

Meldrum’s acids - nitriles - 1,2,4-oxadiazoles - three-component reaction - solvent-free synthesis

    References and Notes

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9

The experiments were performed using a microwave oven (ETHOS 1600, Milestone) with a power of 600 W specially designed for organic synthesis.

11

Preparation of 5-Methyl-3-phenyl-1,2,4-oxadiazole ( 5a); General Procedure.
A mixture of benzonitrile (0.21 g, 2 mmol), NH2OH 50% (0.13 g, 2 mmol), and a catalytic amount of AcOH was irradiated with microwaves at 100 °C for 1 min. After nearly complete conversion to the corresponding amidoxime as was indicated by TLC, Meldrum’s acid (0.29 g, 2 mmol) was added to the reaction mixture and it was irradiated at 150 °C for a further 2 min. After cooling to r.t., the solid residue was sublimated and 5a obtained as colorless crystals. In the case of the products 5d-h, the obtained crude solid were purified by recrystallization from 95% EtOH, and the products 5b,c,i-n were purified by column chromatography (4:1 n-hexane-EtOAc as eluent, Merck silica gel 60 mesh).
Selected Data.
Compound 5a: colorless crystals. 1H NMR (500.1 MHz, CDCl3): δ = 2.60 (3 H, s, CH3), 7.45 (3 H, m, 3 × CH), 8.04 (2 H, dd, J = 7.8 Hz and J = 1.7 Hz, 2 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 12.30 (CH3), 124.01 (C), 127.32, 128.80, and 131.05 (3 × CH), 168.38 (NCN), 176.29 (NCO).
Compound 5d: colorless crystals. 1H NMR (500.1 MHz, CDCl3): δ = 2.36 (3 H, s, PhCH3), 2.58 (3 H, s, CH3), 7.23 (2 H, d, J = 7.8 Hz, 2 × CH), 7.92 (2 H, d, J = 7.8 Hz, 2 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 12.25 (CH3), 21.44 (PhCH3), 124.00 (C), 127.21 and 129.48 (2 × CH), 141.31 (C), 168.32 (NCN), 176.27 (NCO).
Compound 5e: colorless crystals. 1H NMR (500.1 MHz, CDCl3): δ = 2.62 (3 H, s, CH3), 7.37 (1 H, t, J = 7.9 Hz, CH), 7.43 (1 H, dd, J = 8.1 Hz and J = 1.1 Hz, CH), 7.91 (1 H, d, J = 7.7 Hz, CH), 8.03 (1 H, s, CH). 13C NMR (125.8 MHz, CDCl3): δ = 12.30 (CH3), 125.36 and 127.45 (2 × CH), 128.58 (C), 130.11 and 131.09 (2 × CH), 134.92 (C), 167.41 (NCN), 176.78 (NCO).
Compound 5j: colorless oil. 1H NMR (500.1 MHz, CDCl3): δ = 1.40 (3 H, t, J = 7.6 Hz, CH2CH 3), 2.35 (3 H, s, CH3), 2.91 (2 H, q, J = 7.6 Hz, CH2), 7.22 (2 H, d, J = 8.0 Hz, 2 × CH), 7.92 (2 H, d, J = 8.0 Hz, 2 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 10.78 (CH2 CH3), 20.27 (CH2), 21.45 (PhCH3), 124.21 (C), 127.29 and 129.48 (2 × CH), 141.26 (C), 168.22 (NCN), 180.51 (NCO).
Compound 5l: colorless crystals. 1H NMR (500.1 MHz, CDCl3): δ = 1.42 (3 H, t, J = 7.6 Hz, CH3), 2.94 (2 H, q, J = 7.6 Hz, CH2), 7.42 (2 H, d, J = 8.5 Hz, 2 × CH), 7.98 (2 H, d, J = 8.5 Hz, 2 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 10.78 (CH3), 20.30 (CH2), 125.51 (C), 128.69 and 129.11 (2 × CH), 137.15 (C), 167.46 (NCN), 180.91 (NCO).
Compound 5n: colorless crystals. 1H NMR (500.1 MHz, CDCl3): δ = 1.44 (3 H, t, J = 7.6 Hz, CH3), 2.97 (2 H, q, J = 7.6 Hz, CH2), 7.60 (2 H, d, J = 8.5 Hz, 2 × CH), 7.94 (2 H, d, J = 8.5 Hz, 2 × CH). 13C NMR (125.8 MHz, CDCl3): δ = 10.81 (CH3), 20.33 (CH2), 125.59 and 125.98 (2 × C), 128.91 and 132.11 (2 × CH), 167.59 (NCN), 180.98 (NCO).