1-phenyl-3-methyl-5-pyrazolone

After quinine was isolated by French chemists P. Peletier and J. Cavantou in 1820, attempts to synthesize this compound began from the bark of a quinine tree. By the middle of the XIX century, some details of the structure of this alkaloid became known, in particular, Hans Skraup found out that quinine contains a quinoline cycle. After these works, many chemists began to synthesize various simple quinoline derivatives in order to verify the pharmaceutical effect of the resulting preparations. Among the many unsuccessful attempts at certain luck in 1883, the German chemist Ludwig Knorr , who worked with synthesized phenylhydrazine recently at that time, made it. He suggested that the reaction of phenylhydrazine with acetoacetic ester should give a quinoline derivative, which he called "dimethylquinicin" ^[1] :

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The resulting compound turned out to be insoluble in water, but this problem was solved by methylation . The soluble methyl derivative was called “ antipyrine ” and proved to be an effective antipyretic drug that exceeded quinine in this respect, but did not have any therapeutic effect on malaria , although it was noted that it has an effect on neuralgic pains. The difference in physiological action made Knorr doubt the correctness of the initial formula and conduct additional studies of the structure of the resulting compound. Additional studies showed that the studied compound does not belong to quinolines and is a five-membered heterocycle - phenylmethylpyrazolone, and the correct cyclization reaction should be written as follows ^[1] :

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White or light yellow crystalline substance. Soluble in alcohol, methanol, solutions of mineral acids, acetic acid, alkalis. Slightly soluble in boiling water. Insoluble in cold water, ether, petroleum ether. Melting point - 127 ° C, boiling point - 287 ° C (265 mm Hg) ^{[2] [3] [4]} .

Obtained by the interaction of phenylhydrazine:

• with acetoacetamide, then the reaction product is cyclized ^[3] ;
• with methyl or ethyl ether of acetoacetic acid in one stage with the release of 90-95% ^{[5] [6]} .

Used for the synthesis of pyrazolone dyes, phenazone ^[3] .

Since the late 1980s, edaravone has been used to treat acute ischemic stroke ; since 2009, it has been included in the Japanese guideline for the management of acute ischemic stroke (grade B) ^{[7] [8]} .

In May 2017, the U.S. Food and Drug Administration (FDA) allowed the use of the drug to treat amyotropic lateral sclerosis following similar decisions in Japan and South Korea. Later, edaravone received a similar permit in Italy and Canada ^{[9] [10]} .

The substance is a purple diffusing color-forming component. In the process of color photographic manifestation, dyes with a maximum spectral absorption in the range of 509–566 nm are formed from 1-phenyl-3-methyl-5-pyrazolone and its derivatives ^[11] . In practice, the substance was used for this purpose in the early versions of the Kodachrome process ^[12] ; it was also proposed by N. Agokas for tinting black and white papers during development ^[13] .

In analytical chemistry, it is used for the quantitative determination of cyanides; it is also used as a reagent for vitamin B ₁₂ ^[4] .

In histochemistry of enzymes - as a reagent for the detection of cytochrome oxidase ^[4] .

Causes an allergy ^[3] .

• Agokas N.N. Toning in the process of manifestation // Soviet Photo : Journal. - 1971. - October ( No. 10 ). - S. 38 .
• Berkenheim A.M. Workshop on synthetic medicinal and aromatic substances and photoreactive. - M., L .: State Scientific and Technical Publishing House of Chemical Literature, 1942.
• Vasina A. Pyramidon // Chemistry and Life: Journal. - 1965. - No. 7-8 . - S. 174-178 .
• 1-Phenyl-3-methyl-5-pyrazolone: ​​article // Chemical Encyclopedic Dictionary / Ch. ed. Knunyants I.L. - M .: Sov. Encyclopedia, 1983.- S. 613.- 792 p.
• Freistat D.S. Reagents and preparations for microscopy. - M .: Chemistry, 1980 .-- 480 p.
• Cheltsov V.S. , Bongard S.A. Color manifestation of three-layer photosensitive materials. - M .: Art, 1958.

• Klimov S. A., Tarasov V. F., Gordon E. P., Sorokina O. V. RF patent №2106345: Method for producing 1-phenyl-3-methyl-5-pyrazolone (neopr.) . JSC "Caustic". Date of treatment June 4, 2017.
• FDA Approves Edaravone as a Treatment for ALS . ALS Research Forum . Date of treatment June 4, 2017.
• Godowsky jr. L., Mannes LD, Wilder LS US Patent US2252718: Reversal process of color photography . Eastman Kodak Company. Date of treatment June 4, 2017.