3.5- Dimethyl-l-phenylpyrazole

Equimolar amounts of acetylmethylacetylene and phenylhydrazine refluxed 3 hrs. in alcohol containing some HCl 3,5-dimethyl-l-phenylpyrazole. Y 15-85%. F. e., also isomers in different ratios depending on the solvent, s. G. Coispeau, J. Elguero, and R. Jacquier, Bl. 1970, 689 pyrazoles from hydrazines, review, s. ibid. 1970, 2717. 

Biquard and Grammaticakis demonstrated in 1941 that the ultraviolet spectra of 3-methyl- and 3,4-dimethyl-l-phenylpyrazol-5-one were intermediate between those of methylated derivatives of the CH (i.e., 55, R = R — Me) and NH forms (i.e., 56, R = Me, R — H or Me) of the compounds, concluding that the potentially tautomeric compounds exist as mixtures of these forms. However, they did not consider the possible occurrence of an OH form. Other ultraviolet... 

In nitric acid sulfuric acid, 3-methyl-1-phenylpyrazole yields the l-(4-nitrophenyl) derivative (96%), and 5-methyl-1-phenylpyrazole the l-(4-nitro-phenyl) derivative (98%). l-(2-Methylphenyl)- and 3,5-dimethyl-1-phenylpyrazole give low yields (up to 33%) of the 4-nitrophenyl products, but l-(2,6-dimethylphenyl) pyrazole gives l-(2,6-dimethyl-3-nitrophenyl) pyrazole (92%). The l-methyl-2-phenyl and 5-methyl-1-phenylpyrazolium cations are markedly less reactive than the 1-phenylpyrazolium cation, presumably because of steric hindrance to coplanarity of the rings. 

Nitration in acetic anhydride of 3-methyl-l-phenylpyrazole yields the 4-nitro product. 5-Methyl-1-phenylpyrazole gives a mixture of 5-methyl-3-nitro (75%) and 5-methyl-4-nitro-1-phenylpyrazole (25%). 3,5-Dimethyl-, l-(2-methylphenyl)-, and l-(2,6-dimethylphenyl)pyrazole each give the 4-nitro products in 42 and 65% and in unspecified yield, respectively [72JCS(P2)1654]. 

Reaction of the A-nitrosoglycine (394) with acetic anhydride gave the anhydro-5-hydroxy-l,2,3-oxadiazolium hydroxide (395). Reaction with DMAD resulted in formation of the intermediate 1 1 cycloadduct (396) which was not isolated and which lost CO2 under the thermal reaction conditions to give dimethyl l-phenylpyrazole-3,4-dicarboxylate (397) (83MI40300). This reaction is capable of considerable variation in terms of the substituents... 

A number of complexes with ligands related to amides, lactams and antipyrine (2,3-dimethyl-l-phenylpyrazol-5-one), as well as complexes with dicarboxylic acid amides are also known (Table 36), but little structural information is available for them. The diantipyrylmethane complex, UI4-4L-2H20, is probably ionic, [UL4]I4-2H20. 

Table 36 Complexes of Actinide(IV) Compounds with Lactams, Antipyrine (2,3-Dimethyl-l-phenylpyrazol-5-one, ATP) and its Derivatives, and Dicarboxylic Acid Amides...

Synthesis of (53) and (54) proceeds with ease on mixing the relevant reagents (Expts 8.14 and 8.15). /V-Methylation of (54) with dimethyl sulphate in the presence of alkali gives 2,3-dimethyl-l-phenylpyrazol-5-one (antipyrin), which was one of the earliest synthetic antipyretics. 

The parent compound (1) was discovered in 1891 by Tauber, who called it diphenyleneazone, and later phenazone. Unfortunately, the latter name was at one time also used for 2,3-dimethyl-l-phenylpyrazol-5-one (anti-pyrine). More recently 1 has been called 3,4-benzocinnoline and now benzo-[c]cinnoline, using Chemical Abstracts nomenclature. The numbering shown is that currently used Beilstein s Handbuch employed numbering analogous to that used for phenanthrene. 

Abarbi et al. (OOJOC4618) reacted 3-bromopropene and 2-bromomethylacrylic acid ethyl ester with the Grignard reagent derived from 1,5-dimethyl-3//-5-iodo-2-phenylpyrazol-3-one and diisopropyl magnesium, and obtained the corresponding 4-allyl-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one and 2-(l, 5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-17/-pyrazol-4-ylmethyl)acrylic acid ethyl ester, respectively. 

We can now review the use of imidates in place of amides. 2-Aminobenzo-nitrile and methyl JV-methylacetimidate [MeC(NMe)OMe] were boiled with phosphoric oxide in xylene, giving a moderate yield of 2,3-dimethyl-4-imino-3,4-dihydroquinazoline (see 1 and 103), which underwent the Dimroth arrangement to the 4-methylamino isomer when warmed with 1 N sodium hydroxide.130 The imidate (104), obtained by the action of diazomethane on 3-cyanomethyl-4-cyano-5-ethoxalylamino-l-phenylpyrazole (see 15), gave 4-amino-3-cyanomethyl-6-ethoxycarbonylpyrazolo[3,4-d]pyrimidine (see 16) in excellent yield when stirred with cold ethanolic ammonia.131 Similarly, 3-amino-4-cyanopyrazole, refluxed with benzyl thioacetimidate, gave a good yield of 4-amino-6-methylpyrazolo[3,4-d]pyrimidine other thio-imidates reacted similarly.132... 

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