Pyrazolin-5-ones, addition

The addition of diazomethane to 17j -hydroxy-5a-androst-l-en-3-one (7) gives the A -pyrazoline (8) in which the C=N bond is conjugated with the 3-keto group. °°... 

The present method9 affords the methyl ester directly in high yields from 2-pyrazolin-5-ones, which are readily prepared in nearly quantitative yields from readily accessible, /3-keto-esters. In addition, the reaction is simple to carry out, conditions are mild, and the product is easily isolated in a high state of purity. A limitation of the reaction is that only the methyl ester can be made, as other alcohols have been found to give poor yields and undesirable mixtures of products. Table I illustrates other examples of the reaction.10... 

A solution of methylhydrazine in methanol was added dropwise to a solution of dimethyl methoxymethylenemalonate in methanol. The initial reaction was exothermic, and the rate of addition was controlled to achieve reflux. The reaction mixture was kept boiling for an additional 4 hr to give pyrazolecarboxylate (1327) in 81% yield (88JOC810). Arylhydrazono-methylenemalonates gave l-aryl-2-pyrazolin-5-ones in boiling aqueous sodium hydroxide for 12 hr (87GEP3617554). 

IV-Alkyl-substituted phthalimides 9 were easily transformed into mono-, di- or trisubslituted pyrazoles 10 via a one-pot addition/decyclization/cyclocondensation sequence <02JCS(P1)207>. 5-Silylpyrazoles can be prepared from condensation of silylalkynones with hydrazines <02T4975>. Reactions of acylated diethyl malonates with hydrazine monohydrochloride in ethanol afforded 3,4-disubstituted pyrazolin-5-ones <02T3639>. 

The Cl sequence introduced in Chap. 2.2 represents a mild and catalytic access to chalcones. l,3-Diarylprop-2-en-l-ones are bifunctional electrophilic Michael-systems and per se important three-carbon building blocks in synthetic heterocyclic chemistry [33]. Among many classes of five-, six-, and seven-membered heterocycles the underlying principle is always the Michael-addition-cyclocondensation sequence of chalcones and bifunctional nucleophiles [176-181, 222-229]. Furthermore, chalcones can also participate in cycloadditions, as dienophiles and dipolar-ophiles and furnish in the case of 1,3-dipolar cycloadditions with diazo alkanes pyrazolines [230, 231], with azides triazolines [232], with nitrones isoxazolidines [233] with azomethinylides pyrrolidines [234], or with nitriloxides isoxazolines [235]. Therefore, the mild, catalytic access to chalcones by the CIR excellently sets the stage for the development of consecutive MCRs based upon cyclocondensation strategies. 

The photochemical products indicated that ( /Z)-isomerization, intramolecular cyclization, and solvent addition (acetonitrile) occurred. A density functional study of the radical reactions of 3-methyl-l-phenyl-2-pyrazolin-5-one was carried out <1997JPC3769>. 

The tautomeric composition in solution of 4-(arylmethyl)isoxazol-5-one derivatives has been determined on the basis of H NMR and infrared (IR) data. The CH form was predominant in chloroform solution, while the NH and OH forms are more common in polar solvents and in the solid state <1996T1443>. 5-Hydroxy- and 5-amino-2-isoxazo-lines show different tautomeric forms in solution. The presence of cyclic hemiacetal or hemiaminal moieties in such molecules allows the easy cleavage of the C-5-0 bond to form linear structures. Subsequent intramolecular addition of nucleophiles to the C=N bond gives rise to cyclic structures. Compounds 20 exist, in the crystalline state, as the isoxazoline form A. In solution, a ring-ring tautomeric equilibrium was observed between the isoxazoline form A and the pyrazoline form C. The tautomeric ratio depended on steric factors and on the solvent used. The tautomeric equilibrium was established after several days (Scheme 2) <2000CHE722>. 

Addition reactions of diazoalkanes, especially diazomethane, diazopropane, diphenyl-diazomethane and ethyl diazoacetate, onto olefins, substituted with one or two electron-withdrawing groups take place very smoothly affording pyrazolines which upon heating or photolysis can give rise to the corresponding substituted cyclopropanes by elimination of nitrogen. 

If a,j8-unsaturated ketones are condensed with 2-pyrazolin-5-ones the reaction is a Michael addition (eq. 30)686 721 resulting in alkylation. 

As already mentioned, it is possible for 2-pyrazolin-5-ones to react with alkylating agents at N-2 and at the oxygen atom in addition to C-4. If there is no substituent at N-l, this position can also be alkylated. Most alkylations give a mixture of the possible products. However, by alkylation at temperatures of 100-130°, with or without basic catalysts, 2-pyrazolin-5-ones can be converted to 2-alkyl-3-pyrazolin-5-ones in excellent yields (eq. 42). This reaction has been extensively studied... 

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