3,5-dimethylpyrazoles

Scheme 4 shows in a general manner cyclocondensations considered to involve reaction mechanisms in which nucleophilic heteroatoms condense with electrophilic carbonyl groups in a 1,3-relationship to each other. The standard method of preparation of pyrazoles involves such condensations (see Chapter 4.04). With hydrazine itself the question of regiospecificity in the condensation does not occur. However, with a monosubstituted hydrazine such as methylhydrazine and 4,4-dimethoxybutan-2-one (105) two products were obtained the 1,3-dimethylpyrazole (106) and the 1,5-dimethylpyrazole (107). Although Scheme 4 represents this type of reaction as a relatively straightforward process, it is considerably more complex and an appreciable effort has been expended on its study (77BSF1163). Details of these reactions and the possible variations of the procedure may be found in Chapter 4.04. 

It is noteworthy that the only deiodinated product (4-nitro-1,3-dimethylpyrazole) was isolated in a 70% yield (86TH1) by cross-coupling phenylacetylene with 5-iodo-4-nitro-l,3-dimethylpyrazole (Scheme 44). 

To establish the nature of the chlorine migration (intramolecular or intermolec-ular), rearrangement of 54 was carried out in the presence of 4-(phenylethynyl)-1,3-dimethylpyrazole 55 (molar ratio of 54 55 = 2). About 40% of the chlorine migrates to the 5 position of the acceptor molecule 55 (Scheme 107). 

In the 4-substituted 1,3-dimethylpyrazoles with ethynyl group fixed in position 5, the acidity increases with a change in the character of substituents in the series H = NH2 < C CPh < I < Br = Cl. 

Compound (28) presents an unusual long range V( H— H) coupling constant between pyrazole H3 and =CH protons <87AP(320)115>. A systematic study of ortAo-benzylic coupling constants 7Me-c=c-H has been published <92JHC935> 1,3-dimethylpyrazole (—0.55 Hz), 1,4-dimethylpyrazole... 

Pavlik and Kurzweil further studied the phototransposition chemistry of 1-methylpyrazoles in which the various ring carbon atoms are systematically labeled with a second methyl group. The primary products shown in Table 2 and the results of deuterium labeling studies shown in Table 3 confirm that these dimethylpyrazoles undergo only pyrazole to imidazole phototransposition by as many as three distinct permutation pathways. Thus, whereas 1,5-dimethyl-pyrazole 16 transposes by the P4, Pg. and P7 pathways to yield a mixture of 1,5-, 1,2-, and 1,4-dimethylimidazoles 19, 17, and 18 respectively, 1,3-dimethylpyrazole 14 transposes only via the P4 and Pg pathways to form 1,2-and 1,4-dimethylimidazoles 17 and 18. Finally, 1,4-dimethylpyrazole 15 trans-... 

Whereas the condensation of o-iodonitrobenzene with copper acetylides is accompanied by cyclization into isatogens, neither 4-iodo-3-nitro- nor 5-iodo-4-nitro-1,3-dimethylpyrazole gives cyclized products in conditions of acetylide synthesis. Moreover, nitropyrazolylphenylacetylene, as compared with o-nitrotolane, does not undergo thermal, catalytic, or photochemical isomerization to give the fused five-membered rings. 

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