Ethyl acetoacetate reaction with phenylhydrazine

Some reactions of 2,3,4-trisubstituted isoxazolium salts (exemplified by 70) leading to ring transformations, are summarized in Scheme 14.180 Other active methylene compounds such as ethyl acetoacetate and cyano-acetamide give analogous results to those with diethyl malonate products of base-induced ring opening by ethoxide are also obtained. When the reaction with phenylhydrazine is carried out in the presence of sodium hydroxide in ethanol the product is 71, presumably formed via the im-inoketene 72. 

Constitution of the Esters of the (3-Ketocarboxylic Acids and of the P-Diketones.—Ethyl acetoacetate is taken as example. It reacts like a ketone with phenylhydrazine, bisulphite, and other ketone reagents on the other hand it shows an acid reaction, it dissolves in alkalis, and gives the colour reaction with ferric chloride characteristic of ends and also of phenols. From this double behaviour it was formerly concluded that it was either purely ketonic or purely enolic and that the reactions in the other form were to be attributed to a rearrangement caused by the reagents used. The true state of affairs was first disclosed by... 

Solid-phase synthesis of substituted pyrazolones 550 from polymer-bound /3-keto esters 549 has been described (Scheme 68) <2001EJ01631>. Trisubstituted pyrazole carboxylic acids were prepared by reaction of polymer-bound arylidene- or alkylidene-/3-oxo esters with phenylhydrazines <1999S1961>. 2-(Pyrazol-l-yl)pyrimi-dine derivatives were prepared by cyclocondensation of ethyl acetoacetate and (6-methyl-4-oxo-3,4-dihydropyrimi-din-2-yl)hydrazine with aromatic aldehydes <2004RJC423>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted-pyrazolin-5-ones <2002T3639>. Reactions of hydrazines with A -acetoacetyl derivatives of (45 )-4-benzyloxazolidin-2-one (Evans oxazolidinone) and (2R)-bornane-10,2-sultam (Oppolzer sultam) in very acidic media gave pyrazoles retaining the 3(5)-chiral moiety <1999S157>. 

The well-known German chemist, Ludwig Knorr, reported the preparation of the first pyrazolinone in 1883.805 This compound was 3-methyl-l-phenyl-2-pyrazolin-5-one prepared by the reaction of ethyl acetoacetate with phenylhydrazine. In the first publication no structure was proposed, but in a later publication806 structure (VI) was suggested. 

Polymer bound acrylic ester is reacted in a Baylis-Hillman reaction with aldehydes to form 3-hydroxy-2-methylidenepropionic acids or with aldehydes and sulfonamides in a three-component reaction to form 2-methylidene-3-[(arylsulfonyl)amino]propionic acids. In order to show the possibility of Michael additions, the synthesis of pyrazolones was chosen. The Michael addition was carried out with ethyl acetoacetate and BEMP as base to form the resin bound p-keto ester. This was then transformed into the hydrazone with phenylhydrazine hydrochloride in the presence of TMOF and DIPEA [28]. The polymer bound phenol was readily coupled to a variety of allyl halides by using the Pl- Bu to generate a reactive phenoxide [29]. 

---