An Example of Polynomial Expansion: The Reaction of 3(5)-Methyl-1H-Pyrazole with Chloroform and Characterization of the Four Isomers

Abstract

The reaction in phase-transfer catalyzed conditions of 3(5)-methyl-1H-pyrazole with chloroform affords four isomers 333, 335, 355 and 555 in proportions corresponding to the polynomial expansion (a + b)3, with a = 0.6 and b = 0.4, a and b being 3-methyl and 5-methyl proportions. The up (u) and down (d) conformation of the pyrazolyl rings with regard to the Csp3–H atom was established by X-ray crystallography and by 1H-, 13C- and 15N-NMR in solution combined with gauge-including atomic orbitals (GIAO)/B3LYP/6-311++G(d,p) calculations. A comparison with other X-ray structures of tris-pyrazolylmethanes was carried out.

A structural study of new tetrakis(1H-pyrazol-1-yl)methanes

“…3 J H4 = 2.6, 5 J Me = 0.5 H: 7.50 3 J H4 = 1.7, 5 J Me = 0.5 H: 6.21 3 J H5 = 1.6, 4 J Me = 0.8 5Me: 1.75 4 J H4 = 0.9, 5 J H3 = 0.4 a Also other solvents: acetone-d 6 , MeOD; no spin-spin coupling constants (SSCC) were provided. 5 a Very similar chemical shifts (but not SSCC) were reported in reference 12 .…”

“…8,9 Since the amounts we obtained clearly did not obey the polynomial coefficients (it works perfectly for the corresponding four trispyrazolylmethanes, a = 0.6, b = 0.4), 10 we decided to record the 1 H NMR spectrum of the crude reaction product in CDCl 3 and also in C 6 D 6 , because it is known that in this last solvent, the signals of the 3-methyl and 5-methyl groups are more different. 11 The very low global yield (8.2%) indicates that the crude reaction product contains many other compounds amongst them we have identified trispyrazolylmethanes (signals of Csp 3 H between 8.2 and 8.5 ppm), 12 which we have verified does not result from the presence of chloroform in our carbon tetrachloride or from tributylamine. 13 Since the yield to obtain trispyrazolylmethanes is always good, 4,5,6 it can be concluded that it is in the last steps when the reduction (hydrodechlorination) of the 1,1',1"-(chloromethanetriyl)tris(methyl-1H-pyrazoles) to tris(methyl-1H-pyrazol-1-yl)methanes (see Scheme 3) took place most probably via a radical mechanism (see Scheme 1).…”

“…The careful NMR study in solution was made necessary by the unexpected result that 3(5)methyl-1H-pyrazole ( 7) afforded a mixture of three derivatives where the number and positions (3 or 5) of the methyl groups were not evident. In particular there is a contradiction between isolating the 3333 isomer (9) but not the 5555 one (13) while we have isolated the 3555 isomer (12) and not the 3335 one (10). Taking into account what we have mentioned about the difficulty to obtain 2 being related to 5-methyl effect, it is normal to obtain the 3333 isomer (9) and not the 5555 one (13).…”

“…Taking into account what we have mentioned about the difficulty to obtain 2 being related to 5-methyl effect, it is normal to obtain the 3333 isomer (9) and not the 5555 one (13). The fact that we have not isolated the 3335 (10) isomer while we have isolated the 3555 (12) one is not related to their proportions in the crude but to the chromatographic separations.…”

“…X-ray structure B3LYP/6-311++G(d,p) optimized geometry In the case of 3(5)-methyl-1H-pyrazole (7) a much more complex result is expected because there are five possible isomers depending on the position of the methyl group at positions 3 or 5 in the resulting tetrakis derivatives: 3333 (9), 3335 (10), 3355 (11), 3555 (12) and 5555 (13). We repeated three times the syntheses followed by column chromatography.…”