3.5- Disubstituted pyrazoles, tautomerism

Two points must be stressed that a 3-R-pyrazole (199a) gives a 1,5-disubstituted derivative (200) and that often the less abundant tautomeric species (Section 4.04.1.5.1) is the more reactive. It is theoretically possible to use the tautomeric composition to direct the synthesis towards one or another derivative. For instance, if (199a) is the more abundant tautomer, the condition to obtain a large proportion of (200) is that The factors... 

After a paper devoted to GIAO/B3LYP calculations of 13 monosubstituted benzenes and 21 1-substituted pyrazoles [148] that allowed discussion of some structural problems (such as conformation, tautomerism, and structure of salts) we have continued to use this combination of experimental (in solution and in the solid state, CPMAS NMR) and calculated values as a very useful exploratory technique. For instance, we have used II, 13C, and 15NNMR spectroscopy to study compounds 149-154. In para-disubstituted derivatives 149,151,152,153, in the solid state (no free rotation) the signals of the ortho carbons are split (one is close to N2) and, thanks to the calculated values, they can be assigned [149],... 

The most important limitation to this synthetic route is that it can only be used for 3,3-disubstituted cyclopropenes. 3//-Pyrazoles that have hydrogen at C3 undergo an essentially irreversible tautomerization to give the 1//-pyrazole. 

---