AN EXPERIMENTAL APPROACH TO THE MILLS-NIXON EFFECT - TAUTOMERISM OF 3(5),4-POLYMETHYLENEPYRAZOLES

The tautomerism of polymethylenepyrazoles provides an experimental acc ess to the Mills-Nixon effect. The equilibrium constants have been det ermined for three pyrazoles with saturated five, six and seven-membere d fused rings using C-13 NMR spectroscopy: 5 2/98, 6 60/40 and 7 38/62 (the first value corresponds to the tautomer with a formal double bon d in the ring fusion). N-15 NMR chemical shifts are consistent with th ese tautomeric ratios. The Mills-Nixon effect is responsible for the l arge energy difference between both tautomers in the case of 3(5)-meth yl-4,5(3)-trimethylenepyrazole 5. Semi-empirical (MNDO, AM1, PM3) and ab initio calculations (STO-3G) have been carried out on these pyrazol es and on 3(5)-methyl-4,5(3)-dimethylenepyrazole 4. Semi-empirical met hods are unable to describe the behavior of the largest cycle 3(5)-met hyl-4,5(3)-pentamethylenepyrazole 7 correctly, while STO-3G//STO-3G ca lculations conveniently reproduce the experimental evidence.