4- 3-oxobutanoate

Ethoxy carbonyl)-7-nitro Ethyl 2-niethyl-3-oxobutanoate PPA 78 [5]... 

Acetyl-5-chloro-3-phenyl Ethyl 2-benzyl-3-oxobutanoate Cone. H Cl 50-90 [7]... 

Fluorophenyl)-2-(methoxycarbonyl)-5- methyl Methyl 2-(4-fluorophenyl)-3-oxobutanoate 58 [8]... 

NaBFI pellets (10-12 eq.) were added to TFA (25 ml) over 30 min. Hthyl 4-[I-(phcnylsulfonyl)indol-3-yl]-4-oxobutanoate (1.5 mmol) was then added as... 

The systematic lUPAC name of ethyl acetoacetate is ethyl 3 oxobutanoate The presence of a ketone carbonyl group is indicated by the designation oxo along with the appro priate locant Thus there are four carbon atoms m the acyl group of ethyl 3 oxobutanoate C 3 being the carbonyl carbon of the ketone function... 

Conjugate base of ethyl 3 oxobutanoate (weaker base)... 

Carbon is alkylated ia the form of enolates or as carbanions. The enolates are ambident ia activity and can react at an oxygen or a carbon. For example, refluxing equimolar amounts of dimethyl sulfate and ethyl acetoacetate with potassium carbonate gives a 36% yield of the 0-methylation product, ie, ethyl 3-methoxy-2-butenoate, and 30% of the C-methylation product, ie, ethyl 2-methyl-3-oxobutanoate (26). Generally, only one alkyl group of the sulfate reacts with beta-diketones, beta-ketoesters, or malonates (27). Factors affecting the 0 C alkylation ratio have been extensively studied (28). Reaction ia the presence of soHd Al O results mosdy ia C-alkylation of ethyl acetoacetate (29). 

The product described here, 4-(4-chlorophenyl)butan-2-one, was previously prepared in the following ways a) by reduction of the corresponding benzalacetone, b) by catalyzed decarbonylation of 4-chlorophenylacetaldehyde by HFeiCO) in the presence of 2,4-pentanedione, - c) by reaction of 4-chlorobenzyl chloride with 2,4-pentanedione under basic catalysis (K2CO3 in EtOH), d) by reaction of 4-chlorobenzyl chloride with ethyl 3-oxobutanoate under basic catalysis (LiOH), - and e) by reaction of 3-(4-chlorophenyl )-propanoic acid with methyl lithium. - ... 

Conjugate base of Hydronium ion Ethyl 3-oxobutanoate Water... 

To a solution of methyl 3-oxobutanoate 127 (580 mg, 5 mmol) and l-methyl-2-methylthio-l//-imidazole-5-carboxaldehye 128 (390 mg, 2.5 mmol) in 5 mL of absolute methanol was added a solution of ammonium hydroxide (25%, 0.4 mL). The reaction was heated at reflux overnight before cooling to room temperature and removing the solvent. The crude product was purified by preparative TLC to afford 526 mg of dimethyl l,4-dihydro-2,6-dimethyl-4-(l-methyl-2-methylthio-5-imidazolyl)-3,5-pyridine-dicarboxylate 129 (60%) as a solid, mp = 200-201 °C (MeOH). 

Comprehensive work in this field has been done by Slovak authors (98MI1, 95M1359, 96CCC269, 96CCC371, 97CCC99). They prepared 2-substituted (H, Me, Ph) 4-, 5-, 6-, and 7-nitrobenzoxazoles, which were then reduced to amines (not isolated) and subjected to subsequent nucleophilic substitution with activated enol ethers such as alkoxymethylene derivatives of malonic acid esters and nitrile, 3-oxobutanoic acid esters, pentanedione, or cyanoacetic acid esters to yield aminoethylenes 8. 

Katritzky and co-workers studied the mechanism of this reaction in detail. His work involved a NMR study of 16 reactions of methyl-, phenyl-, 1,2-dimethyl-, and l-methyl-2-phenylhydrazine with /3-keto esters. In many cases starting materials, intermediates, and products were detected simultaneously. Most reactions proceed by nucleophilic addition of the less hindered hydrazine nitrogen atom to the keto carbon of the keto ester. For example, the pathway given in Scheme 3 for the reaction of methyl 3-oxobutanoate 9 with methyl- or phenyUiydrazine 2 (R = Me or Ph) was found to be dominant. The initially formed addition product 10 dehydrates to hydrazone 11, which then isomerizes to hydrazone 12. Intermediate 12 then cyclizes to pyrazol-3-one 13, which tautomerizes to the kinetically more stable pyrazol-3-otie 14 [87JCS(P2)969]. 

Copper(Il) complexes 18a-f of methyl or ethyl 3-oxobutanoate la, 2-bromo-3 oxobutanoate lb, 2-(anilinocarbonyl)-3-oxobutanoate Ic, 3-oxo-3- rfienylpro-panoate Id, 2-bromo-3-oxo-3-phenylpropanoate le, or 3-aniHno-2-benzoyl-3-oxopropanoate If were reacted with phenylhydrazine hydrochloride and sodium ( )... 

Benzyl or n-propyl)-5-methyl-3W-pyrazole-3,4-dione 4-oximes 31a,b were prepared by two routes. Thus, efliyl 3-oxobutanoate 27 was eiflier heated wifli... 

A -benzyl or W-propyl-/V-nitrosohydrazir es 28a,b at 50 C for 6 days ot nitrosated to ethyl 2-(hydroxyimino)-3-oxobutanoate 29 which was then heated with benzyl-hydrazine 30a OT n-propylhydrazine 30b in ethanol (87JOU1773) (Scheme 8). 

Krohn and Stenns reacted ethyl 3-oxobutanoate with l-(4-methoxyphenyl)hy-drazine 32 and managed to obtain pyrazol-3-one 33 and pyrazole 34 in 65 and 20% yield, respectively (89AP351) (Scheme 9). 

Hydrazones that are formed by heating the y3-keto ester and the hydrazine in an alcohol usually require more vigorous conditions in order to cyclize to pyrazol-3-ones. Thus, hydrazone 52, obtained by heating oxobutanoate 51 and phenylhy-drazine in ethanol, required heating under reflux in benzene ccMitaining phosphorus pentoxide in order to cyclize into l,2-dihydropyrazol-3-one 53 (66JOU1103) (Scheme 16). 

The reaction of ethyl 3-oxobutanoate with 4-aryltetrahydropyridazine-3,6-di(Mie 3-hydrazones 60a-d afforded the corresponding hydrazonobutanoates 61a-d. When heated with ethanolic sodium ethoxide, compounds 618-d cyclized to the sodium derivatives 62a-d which, upon acidification, gave the respective pyrazol-3-one derivatives 63a-d (97JHC389) (Scheme 19). 

A widely used approach is the condensation of (amino, methylamino, or ethyl-amino)benzohydrazides 73a with ethyl 3-oxobutanoate in boiling ethanol... 

In the reaction of arylhydrazides 73a, benzylhydrazide 73b, aryloxymethylhy-drazides 73c, or 1 -styrylhydrazide 73d with ethyl 3-oxobutanoate in boiling diox-ane, the corresponding hydrazones 86a-d were obtained in good yields. The latter... 

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