Knorr pyrazolone

Fig. 4.13. illustrates how to apply carbon-13 NMR for analysis of tautomerism in heterocyclic chemistry 3-Methyl-5-oxo-l-phenyl-4,5-dihydropyrazole (the Knorr-pyrazolone ) is shown to exist as the CH tautomer B with a CH2 carbon at 43.1 ppm in chloroform solution (Fig. 4.13(a)), while the OH tautomer A predominates (90%) in hexadeuteriodimethyl sulfoxide (Fig. 4.13(b) [73 i]. 

Knorr reported the first pyrazole derivative in 1883. The reaction of phenyl hydrazine and ethylacetoacetate resulted in a novel stmcture identified in 1887 as l-phenyl-3-methy 1-5-pyrazolone 9. His interest in antipyretic compounds led him to test these derivatives for antipyretic activity which led to the discovery of antipyrine 10. He introduced the name pyrazole for these compounds to denote that the nucleus was derived from the pyrrole by replacement of a carbon with a nitrogen. He subsequnently prepared many pyrazole analogs, particularly compounds derived from the readily available phenyl hydrazine. The unsubstituted pyrazole wasn t prepared until 1889 by decarboxylation of liT-pyrazole-3,4,5-tricarboxylic acid. ... 

Reaction of hydrazine or substituted hydrazine with 1,3-dicarbonyl compounds to provide the pyrazole or pyrazolone ring system. Cf. Paal-Knorr pyrrole synthesis (page 333). 

Knorr, L. Ber Dtsch. Chem. Ges. 1883, 16, 2597. Ludwig Knorr (1859—1921) was bom near Munich, Germany. After studying under Volhard, Emil Fischer, and Bunsen, he was appointed professor of chemistry at Jena. Knorr made tremendous contributions in the synthesis of heterocycles in addition to discovering the important pyrazolone drug, pyrine. 

This reaction was first reported by Knorr in 1883. It is the preparation of pyrazole derivatives from 1,3-dicarbonyl compounds and hydrazines. Similarly, pyrazole derivatives can also be prepared from hydrazines and equivalent molecules of 1,3-dicarbonyl compounds, such as a-ethoxymethylene a-phenylacetone. In a special case, -carbonyl aldehyde reacts with a simple hydrazine to afford tautomers of 3- and 5-substituted pyra-zoles, of which the proton oscillates rapidly back and forth between two nitrogen atoms. These two tautomers are distinguishable only at sufficiently low temperatures." It should be pointed out that the reaction of hydrazine with j8-carbonyl ester leads to the formation of pyrazolone. ... 

Ludwig Knorr (Munich, 2 December 1859-Jena, 5 June 1921), a pupil of Baeyer, Bunsen, and Emil Fischer, was associate professor in Wurzburg (1888) and professor in Jena (1889). much work on pyrazolones... 

---