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Synlett 2003(7): 1064-1066
DOI: 10.1055/s-2003-39322
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 1,2,4-Oxadiazolines on Soluble Polymer Support

Yong-Jia Shang, Wang-Ge Shou, Yan-Guang Wang*
Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
Fax: +86(571)87951512; e-Mail: orgwyg@css.zju.edu.cn;
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Publication History

Received 7 April 2003
Publication Date:
20 May 2003 (online)

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Abstract

A general method for the liquid-phase syntheses of 1,2,4-oxadiazolines through a 1,3-dipolar cycloaddition is described. The poly(ethylene glycol) (PEG)-supported imines reacted with nitrile oxides generated in situ from aldoximes, and then the adducts were cleaved from the PEG, to give 1,2,4-oxadiazolines in high yields and excellent purities.

Key words

poly(ethylene glycol) (PEG) - oxadiazolines - imines - cycloaddition - liquid-phase

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19

The polymer supported aldehyde was characterized by 500 MHz 1H NMR analysis in CDCl3:δ = 8.19 (s, 1 H), 8.12 (d, J = 8.3 Hz, 2 H), 7.71 (d, J = 8.3 Hz, 2 H), 4.53 (t, J = 4.7 Hz, 2 H, -PEGOCH2CH 2CO), 3.70-3.90 (m, PEG) ppm. The polymer supported imine 2c (R = p-FC6H4) was characterized by 500 MHz 1H NMR analysis in CDCl3: δ = 8.51 (s, 1 H), 8.15 (d, J = 8.1 Hz, 2 H), 7.96 (d, J = 8.1 Hz, 2 H), 7.26 (m, 2 H), 7.11 (m, 2 H), 4.51 (t, J = 4.7 Hz, 2 H, -PEGOCH2CH 2CO), 3.50-3.78 (m, PEG) ppm.

20

Typical Procedure for the Synthesis of 1,2,4-Oxadiazolines: N-Chlorosuccinimide (NCS, 2 mmol) was stirred in a flask containing dry CH2Cl2 (5 mL). The oxime (2 mmol) was added at 25 °C in one portion.The polymer-supported acrylate (0.25 mmol) was added in one portion after the chlorination was over. Usually after ca 30 min, Et3N (0.14 mL in 2 mL of CH2Cl2) was added drop by drop over ca 2 h. The reaction mixture was stirred overnight at r.t. To this was added a five fold excess of dry benzene and the resulting triethylamine hydrochloride was removed by filtration. The solution was concentrated and Et2O was added to afford the polymer-supported 1,2,4-oxadiazolines 3. The resin 3 is then cleaved with CH3ONa/CH3OH at r.t. to give the desired 1,2,4-oxadiazolines 4. Compound 3a:
1H NMR (500 MHz, CDCl3): δ = 8.13 (d, J = 8.0 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 2 H), 6.80-7.10 (m, 5 H), 6.54 (s, 1 H), 4.25 (t, J = 4.7 Hz, 2 H, -PEGOCH2CH 2CO), 3.80 (s, 3 H), 3.50-3.78 (m, PEG) ppm. Compound 4a: 1H NMR (500 MHz, CDCl3): δ = 8.11 (d, J = 8.0 Hz, 2 H), 7.67 (d, J = 8.0 Hz, 2 H), 7.53 (d, J = 8.5 Hz, 2 H), 7.18 (d, J = 8.4 Hz, 2 H), 6.80-7.10 (m, 5 H), 6.54 (s, 1 H), 4.11 (s, 3 H), 3.88 (s, 3 H) ppm. GC/MS: m/z = 388 (M+).