5-Pyrazolones hydrazones

When ethyl acetoacetate is warmed with an equivalent quantity of phenyl-hydrazine, the compound (I), which is not a true hydrazone, is first formed this undergoes ring formation (II) with loss of ethyl alcohol upon further heating. The product (II) is N or l-phenyl-3-methyl-5-pyrazolone. 

Condensation of Selenated Alkylidene or Benzylidene Hydrazones or Pyrazolones with p-nitroso Dialkyanilines... 

Despite the inconveniences, a certain number of studies have been carried out, particularly concerning dyes containing azomethine groups. Such as hydrazones, pyrazolones, formazans, and selenazoles quinoids. Saturated heterocycles, that is, selenazolines and selenazolidines. have also been tackled. Selenium derivatives for pharmacological or physiological applications are little developed by comparison with their thiazole homologs. 

The most important synthesis of pyrazolones involves the condensation of a hydrazine with a P-ketoester such as ethyl acetoacetate. Commercially important pyrazolones carry an aryl substituent at the 1-position, mainly because the hydrazine precursors are prepared from readily available and comparatively inexpensive diazonium salts by reduction. In the first step of the synthesis the hydrazine is condensed with the P-ketoester to give a hydrazone heating with sodium carbonate then effects cyclization to the pyrazolone. In practice the condensation and cyclization reactions are usually done in one pot without isolating the hydrazone intermediate. 

Preparation of thiadiazoles via the Hurd-Mori cyclization has led to the synthesis of a variety of biologically active and functionally useful compounds. Discussion of reactions prior to 1998 on the preparation of thiadiazoles have been compiled in a review by Stanetty et al Recent syntheses of thiadiazoles as intermediates for useful transformations to other heterocycles have appeared. For example, the thiadiazole intermediate 36 was prepared from the hydrazone 35 and converted to benzofuran upon treatment with base. Similarly, the thiadiazole acid chloride 38 was converted to the hydrazine 39 which, upon base treatment, provided the pyrazolone, which can be sequentially alkylated in situ to provide the product 40. ... 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

Michael-type condensation of cyanoacetohydrazide (NCCH2CONHNH2, CAH) with 1,3-dicarbonyl compounds gave pyrazolo[3,4-b]pyridines under certain conditions. With l,l,l-trifluoropentane-2,4-dione in the presence of piperidine a 1 3 mixture of pyrazolone 92a and the expected aminopyridone 91a was obtained.15 The bicycle was also obtained from hydrazone (90) or by thermal reaction between its two precursors.32 Reaction of CAH and / -keto aldehydes gave good yields of only bicyclic products 92b,20 whereas ethyl benzoylacetate in the presence of piperidine gave bicycle 92c (Ar = Ph)... 

No isomers were detected in the copper and nickel complexes of the strongly polarized o,o -dihydroxyazobenzene (89), the l-(2-hydroxyphenylazo)-2-naphthols (90), or the 1-phenyl-3-methyl-4-(2-hydroxyphenylazo)-5-pyrazolones (91). These compounds exist predominantly in the quinone hydrazone (92 and 93) and ketone hydrazone (94) forms, respectively (Section... 

The hydrazone then loses C2H6OH and forms l-phenyl-3-raethyl pyrazolon ... 

The group of Tietze has described syntheses of variously substituted pyrazolones 20 starting from solid-phase-bound p-keto esters. Single or iterative alkylation of the dianion of immobilized acetoacetate with allyl-, benzyl- or alkyl halides produced a set of y-substituted ketoesters 18 that could be transformed to the phenyl-hydrazones 19. Treatment of these intermediates in toluene at 100 °C produced 1-phenylpyrazolone derivatives 20 in 40-75% yield (Scheme 6) [14]. 

The same group reported an approach to trisubstituted pyrazolones beginning with a solution-phase acylation of Meldrum s acid 21 and resin-capturing of the intermediates 22 with the add-stable resin 27. The products 23 were a-alky-lated using tetrabutylammonium fluoride (TBAF) and primary alkyl halides under strict exclusion of moisture, as otherwise the yields dropped dramatically. Treatment of the products 24 with phenyUiydrazines produced the corresponding hydrazones 25, which were cleaved from the solid phase by cyclization using 2% TFA in acetonitrile at room temperature to form pyrazolones 26 [15[ (Scheme 7). 

Due to the presence of two functional groups, there is a wide range of possible postmodifications. One possibility is the conversion of the double bond, as in the Michael addition of amines leading to 1,3-amino-alcohols [19], by epoxidation or a Michael addition of a P-ketoester to form pyrazolones [23] after the conversion into hydrazones, followed by an intramolecular cyclization. 

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]. 

In the presence of a catalytic amount of Sc(OTf)3, benzoylhy-drazones react with ketene silyl acetals to afford the corresponding adducts, 8-lV-benzoylhydrazino esters, in high yield (eq 10). Several benzoylhydrazones including those derived from aromatic, aliphatic, a,/3-unsaturated aldehydes, and glyoxylate work well. The reactions of polymer-supported hydrazones with silyl enolates are also catalyzed by Sc(OTf)3 to produce pyrazolone derivatives after base treatment. ... 

For ketoester the substrate, the hydrazone forms exclusively between the hydrazine and with more active ketone. The corresponding hydrazone-ester then cyclizes to produce the pyazolone. Mechanistically, the more basic and less substituted hydrazine amine condenses with the ketone. The resultant hydrazine-ester then cyclizes to the pyrazolol, which could also tautomerize to the corresponding pyrazolone. 

To reduce this disadvantage while keeping the advantage of the positive characteristics such as non-bleeding character, studies of syntheses of Naphthol AS series polymeric azo dyes (l) and Pyrazolone polymeric azo dyes containing polymerizable group in diazo component (2) have been carried out. It was proved that the influence of polymerization to light fastness of the dyes was correlated with azo-hydrazone tautomerism of azo dye, and that the influence was not observed in the azo dye such as equilibrium shifted to hydra-zone form. 

A suspension of l,3-diphenyl-4-methyl-4-(4 -chlorophenylazo)-5-pyrazolone in glacial acetic acid treated with Zn-dust during 5 min., and stirring continued for 5 min. 4-chlorophenylhydrazine (Y 79% as the hydrazone of 4-nitrobenz-aldehyde) and l,3-diphenyl-4-methyl-5-pyrazolone (Y 75%). F. e. s. W. Pelz et al., Ang. Gh. 72, 967 (I960). 

Pyrazolones from y -ketocarboxylic acid amides via y -ketocarboxylic acid amide hydrazones... 

Methoxyphenylhydrazine hydrochloride added to acetoacetamide and aq. NHg, stirred 1 hr., acidified with HGl to pH 3, and stirred 30 min. at 50° l-(4-methoxyphenyl)-3-methyl-5-pyrazolone. Y 97%.—In an acid medium, hydrazones of acetoacetamide have a higher activity than other derivatives of acetoacetic acid, such as esters, whereas in alkaline medium they have the lowest activity. F. e. s. P. A. Levin, Zh. Prik. Khim. 3A, 2803 (1961) G. A. 56, 12871g. 

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