Regioselective synthesis of unsymmetrical 3,5-dialkyl-1-arylpyrazoles

Organic Letters

Volumn 2, Issue 20, 2000, Pages 3107-3109

  Wang, Xiao Jun ^a   Tan, Jonathan ^a   Zhang, Li ^a  

^a BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0000385688     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol0001822     Document Type: Article

References (14)

1. (a) Kost, A. N.; Grandberg, I. I. In Progress in Pyrazole Chemistry; Kartrizky, A. R., Boulton, A. J., Eds.; Advances in Heterocyclic Chemistry; Academic Press: New York, 1966; Vol. 6, p 347.
2. (b) Elguero, J. In Pyrazoles and their Benzo Derivatives; Katrizky, A. R., Rees, C. W., Eds.; Comprehensive Heterocyclic Chemistry; Pergamon Press: Oxford, 1984; Vol. 5, p 167.
3. Wang, X.-j.; Tan, J.; Grozinger, K.; Belageri, R.; Kirrane, T.; Proudfoot, J. R. Tetrahedron Lett. 2000, 41, 5321.
4. Malhotra, N.; Falt-Hansen, B.; Becher, J. J. Heterocycl. Chem. 1991, 28, 1837.
5. (a) Brunner, H.; Scheck, T. Chem. Ber. 1992, 125, 701.
6. (b) Luo, Y.; Potvin, P. G. J. Org. Chem. 1994, 59, 1761.
7. (c) Tarrago, G.; Ramdani, A. J. Heterocycl. Chem. 1980, 17, 137.
8. (d) Khan, M. A.; Lynch, B. M. J. Heterocycl. Chem. 1970, 7, 1237.
9. Pyrazoles 5-8 were made from condensation of their corresponding propargylic ketones with hydrazine and used directly without purification.
10. The structures of all regioisomers were supported by NOE experiments.
11. Elguero, J.; Gonzalez, E.; Jacquier, R. Bull. Soc. Chim. Fr. 1968, 707.
12. 3-tert-Butyl-5-ethylpyrzole (22) was subjected to the same N-arylation with 4-fluoronitrobenzene to give 1-(4-nitrophenyl)-3-tert-butyl-5-ethyl-pyrzole (23) as a single regioisomer.
13. Chavez, F.; Godinez, R. Synth. Commmun. 1992, 22, 159.
14. To support our rationale, N-arylation of 5 was carried out using KOt-Bu as base in the presence of 1 equiv of 18-crown-6 in refluxing THF. The reaction gave a 1:1 mixture of regioisomers 5a and 5b, in contrast with a 7:1 mixture obtained without 18-crown-6.