N-methylpyrazole

Nguyen, D.H., J. W. Szewczyk, E.E. Baird, and P. B. Dervan. Alternative heterocycles for DNA recognition An N-methylpyrazole/N-methylpyrrole pair specifies for A-T/T-A base pairs. Bioorg. 

Further examples have accumulated. The reactions of oxazoles (257), selenophene (258), and N-methylpyrazole (261) with tetrazine (48) form (256) and (260), (259), and (262) respectively, partly after oxidation (Scheme 47) <88CZ17>. The reactions of 3,6-bis(trifluoromethyl)tetrazine with imidazoles, oxazoles, pyrazoles <89AP(322)415>, indole, and benzo[Z>]thiophene <87CZ8l,87JOC4610> have also been studied. 

On irradiation, pyrazoles rearrange to imidazoles and undergo ring-opening to P-aminoacrylonitriles. For these photoisomerizations, various mechanistic pathways have been discussed [431], as exemplified for the transformation of N-methylpyrazole leading to N-methyhmidazole (12) and the nitrile 14. 

Seitz G, Hoferichter R, Mohr R (1989) Imidazoles, oxazole and N-methylpyrazole as dieno-philes in the Diels-Adler-cycloaddition with inverse electron demand. Arch Pharm 322 415-417... 

Dimerizations of p-Rich N-Heteroaromatic Compounds and Xanthine Derivatives. Sekine, Toshikazu Higuchi, Yoshihiro Yamada, Tomoko Murakoshi, Isamu (Fac. Pharm. Sci., Chiba Univ., Chiba, Japan 260). Chem. Pharm. BuU. 1989, 37 (8) 1987-9 (Eng.). N-Methylimidazole, benzimidazole, and N-methylbenzimidazole condensed dehydrogenatively to afford the corresponding sym. dimers when heated in the presence of Pd-Pt/C catalyst and pyridine N-oxide. Imidazole, pyrazole, and N-methylpyrazole did not dimerize under the same conditions. The same reactions using caffeine and 1,7-dimethylhypoxanthine gave the eorresponding dimers. 

Pyrazole and its C-methyl derivatives acting as 2-monohaptopyrazoles in a neutral or slightly acidic medium give M(HPz) X, complexes where M is a transition metal, X is the counterion and m is the valence of the transition metal, usually 2. The number of pyrazole molecules, n, for a given metal depends on the nature of X and on the steric effects of the pyrazole substituents, especially those at position 3. Complexes of 3(5)-methylpyrazole with salts of a number of divalent metals involve the less hindered tautomer, the 5-methylpyrazole (209). With pyrazole and 4- or 5-monosubstituted pyrazoles M(HPz)6X2... 

Pyrimidine, 4-methoxy-2-( 5-methoxy-3-methylpyrazol-I-yl)-6-methyl-analgesic activity, 5, 294 Pyrimidine, 2-methoxy-5-methyI-rearrangement, 3, 93 Pyrimidine, 4-methoxy-6-methyl-N-oxides... 

The composition of the mixture of products of different structures depends on the diacetylene diazomethane ratio (68LA124). With a 1 1 ratio of butadiyne and diazomethane, 3(5)-ethynylpyrazole dominates (55%). The yields of isomeric 3- and 5-ethynyl-l-methylpyrazoles are 8 and 11%, respectively. The double excess of diazomethane leads mainly to a mixture of N-methylated isomers (81%), 10% of 3(5)-ethynylpyrazole, and a small amount (3%) of bipyrazole (68LA124) (Scheme 3). 

By the chlorination of 3-ethynyl-, 4-ethynyl-, and 5-ethynyl-l-methylpyrazole with KOCl the corresponding compounds were synthesized in 98%, 100%, and 94% yields. The typical procedure is as follows To an aqueous solution of KOX (0.64 N) in 12.5% KOH, prepared from the corresponding halogen and potassium hydroxide in water at 5-10°C, was added the terminal acetylene, followed by stirring at room temperature until the complete disappearance of the starting material. 

Each of the tautomeric forms of a substance may show electronic resonance tautomerism and resonance are not mutually exclusive. Let us discuss 5-methylpyrazole as an example. This substance exists in two tautomeric forms, A and B, differing in the position of the N-hydrogen atom. 

When protected with suitable N-substituents, pyrazoles undergo an a-metalation at the 5-position similar to that seen with pyrroles (Scheme 33)(790R1 88CHE117, 88KGS147). With 1-methylpyrazoles metalation... 

Brent J, McMartin K, Phillips S, Burkhart KK, Donovan JW, Wells M et al. Fomepizole for the treatment of ethylene glycol poisoning. Methylpyrazole for Toxic Alcohols Study Group. N Engl J Med 1999 340(11) 832-8. 

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