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Synlett 2012(6): 935-937  
DOI: 10.1055/s-0031-1290608
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 3-Trifluoromethyl-1,4-dihydropyridazines by the PTSA-Catalyzed Reaction of α,β-Unsaturated Aldehydes with (E)-1-Phenyl-2-(2,2,2-trifluoroethylidene)

Haibo Xie, Jiangtao Zhu, Zixian Chen, Shan Li, Yongming Wu*
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 LingLing Road, Shanghai 200032, P. R. of China
Fax: +86(21)54925192; e-Mail: ymwu@sioc.ac.cn;
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Publication History

Received 19 December 2011
Publication Date:
15 March 2012 (online)

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Abstract

A facile and efficient method for the synthesis 3-trifluoromethyl-1,4-dihydropyridazine from a variety of readily available α,β-unsaturated aldehyde and (E)-1-phenyl-2-(2,2,2-trifluoroethylidene)hydrazine was developed. The reaction proceeded under mild conditions and gave the expected 1,4-dihydropyridazine products in moderate to high yields.

Key words

pyridazine - 3,3-sigmatropic rearrangement - electro­cyclic rearrangement - hydrazine - heterocycles

    References and Notes

  • 1a Kolar P. Tiler M. In Advances in Heterocyclic Chemistry   Vol. 75:  Katritzky AR. Academic Press; San Diego: 2000.  p.167 
    Search in Google Scholar
  • 1b Brown DJ. In Chemistry of Heterocyclic Compounds   Vol. 57:  Taylor EC. Wipf P. Wiley; New York: 2000.  p.1 
    Search in Google Scholar
  • 1c Maes BUW. Lemière GLF. In Comprehensive Heterocyclic Chemistry   3rd ed., Vol. 8:  Aitken A. Elsevier; Amsterdam: 2008.  p.1 
    Search in Google Scholar
  • 2a Knorr L. Ber. Dtsch. Chem. Ges.  1885,  299 
  • 2b Fischer E. Justus Liebigs Ann. Chem.  1886,  147 
  • 2c Tauber E. Ber. Dtsch. Chem. Ges.  1895,  451 
  • 3a Tišler M. Stanovnik B. Adv. Heterocycl. Chem.  1968,  211 
  • 3b Hunston RN. Parrick J. Shaw CJG. In Rodd’s Chemistry of Carbon Compounds   Vol. 4:  Coffey S. Elsevier; Amsterdam: 1989.  p.1 
    Search in Google Scholar
  • 4a Mathew T. Keller M. Hunkler D. Pinzbach H. Tetrahedron Lett.  1996,  4491 
  • 4b Mathew T. Tonne J. Sedelmeier G. Grund C. Keller M. Hunkler D. Knothe L. Pinzbach H. Eur. J. Org. Chem.  2007,  2133 
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General Procedure for the Fluorination of 1,4-Dihydropyridazine
A Schlenk tube was charged with PTSA (19 mg, 0.1 mmol), evacuated and backfilled with nitrogen. Toluene (5.0 mL), cinnamaldehyde (132 mg, 1.0 mmol), and (E)-1-phenyl-2-(2,2,2-trifluoroethylidene)hydrazine (5, 188 mg, 1.0 mmol) was successively added. Then the reaction mixture was stirred at r.t. for 12 h. The mixture was partitioned between EtOAc and H2O, the organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by column chromatography on silica gel and crystallized from PE (boiling range 60-90 ˚C) to provide 7b. General Analytical Data of Compound 7b
¹H NMR (300 MHz, CDCl3): δ = 7.41-7.22 (m, 9 H), 7.15-7.11 (m, 1 H), 6.90 (d, J = 7.6 Hz, 1 H), 5.22 (dd, J 1 = 7.6 Hz, J 2 = 5.3 Hz, 1 H), 4.40 (d, J = 5.3 Hz, 1 H). ¹9F NMR (282 MHz, CDCl3): δ = -67.7 (s). ¹³C NMR (100 MHz, CDCl3): d = 143.6, 142.8, 132.9 (q, J = 34.2 Hz), 129.3, 128.9, 127.5, 124.6, 123.9, 121.5 (q, J = 275.3 Hz), 119.6, 116.2, 104.7, 36.5. IR (KBr): 3060, 2912, 2843, 1666, 1599, 1493, 1480, 1289, 1271, 1223, 1173, 1129, 1076, 983, 755, 697 cm-¹. MS (EI): m/z (%) = 302 (20)[M+], 225 (100), 205 (9), 105 (5), 77 (25). HRMS: m/z calcd for C17H13F3N2: 302.1031; found: 302.1030.