Pyrazole —continued from hydrazines

Syntheses of fluoro-substituted pyrazoles continue to be of interest. Both 3- and 5-fluoropyrazoles (44 and 45, respectively) can be prepared from 43 <96JOC2763>. Treatment of 43 with hydrazine followed by N-alkylation provides 44, whereas reactions with monosubstituted hydrazines afford 45. The 4-(trifluoromcthyl)pyrazoles 47 are obtained from J-trifluoromethyl vinamidinium salt 46 <96TL1829>. The 5-trifluoromethyl-3-carboethoxypyrazoles 49 are obtained from the 1,3-dipolar cycloadditions of trifluoromethyl alkenes 48 with ethyl diazoacetate <96T4383>. 

In continuing efforts to develop more general and versatile methods for the synthesis of pyrazoles contained in natural products, and at the same time to use microwave irradiation, instead of conventional heating, particularly the solvent-free technique, because it provides the opportunity to work with open vessels, Yadav et al. [85] prepared a new class of optically pure 4-substituted pyrazoles 128 from 2-formyl glycols 127 and aryl hydrazines (Scheme 12.52). 

The same classification as in CHEC-I <84CHEC-I(5)167> is be followed. It is clear that two methods of preparing pyrazoles and their derivatives continue to dominate all other methods, in both the two nitrogen atoms come from one of the reagents, either hydrazine (see Section 3.01.10.1.2(ii) (CCC -f NN)) or a 1,3-dipole, diazoalkane, nitrilimine, etc. (see Section 3.01.10.1.2(h) CNN CC)).. The other methods are curiosities mostly discovered by hazard or variations of these two great principles. 

An important application of thermodynamic control occurs in the manufacture of Viagra 12, Pfizer s treatment for impotence.3 The NE corner of the molecule comes from the pyrazole acid 13 removal of the hydrazine portion reveals the one piece of continuous carbon skeleton 14. 1,3-Dicarbonyl disconnection gives an unenolisable diester (an oxalate) and an unsym-metrical ketone, pentan-2-one 15. 

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