3- Pyrazolin-5-ones addition reactions

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. 

A synthesis of the 17/3-[3-pyrrolin-2-on-4-yl]androstane (361) from acetyl-digitoxigenin (339) has been reported. The conversion of the iV-acetyl compound (362) into dihydrosolacongestidine (363) was improved by use of BU2AIH and thereby improved the synthesis of solacongestidine (364). Addition of diarylnitrilimines to a series of 17-substituted androst-16-enes gave the [16a,17o -f ]-2 -pyrazolines (365) or, when R = OAc, the [16,17-rf]-pyrazoles (366). The pyrazolines (367) were synthesized from 3/3-acetoxy-21-benzylidenepregn-5-en-20-one by reaction with phenyl- or p-methoxyphenyl-hydrazine. " Reaction of cholest-4-en-6-one with hydrazines and o-phenylenediamine led to the heterocyclic structures (368) and (369)... 

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 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>. 

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... 

The reaction of zinc with 2,3-dimethyl-l-phenyl-3-pyrazolin-5-one has been reported by Knorr807 to give benzene, aniline and unidentified products. Heymons and Rohland647 treated l,2-diphenyl-3-methyl-3-pyrazolin-5-one with metallic sodium, obtaining addition of sodium at the 1,4-position of the conjugated system present (eq. 132). 

Pyrazolin-5-ones react with salts of various metals to form compounds in which the pyrazolinone has reacted in its enolic form with replacement of the enolic hydrogen to give a salt and having semipolar bonds formed by donation of electrons to the metal by the nitrogen atoms393 394 Usually these compounds contain the number of pyrazolinone residues corresponding to the valence of the metal atom. Such salts as cuprous iodide, ferric iodide, cobaltous iodide, silver iodide and silver diiodide participate in such reactions.393,394 In addition, complexes may be formed in which there has been no elimination of a small molecule between the reactants and no formation of ionic bonds.432... 

The reaction of 2-phenyl-4-benzylidene-5-oxazolone with hydrazine forms 4-benzamido-5-phenyl-3-pyrazolidinone.319,1342 Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones have been reduced catalytically to 3-pyrazolidinones.1491,1592 Heymons and Rohland647 have treated 3-methyl-l,2-diphenyl-3-pyrazolin-5-one with sodium and carbon dioxide and claimed to have obtained a carboxylic acid, presumably by intermediate addition of sodium to the double bond (eq. 246). A number of... 

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