Aldehydes reaction with 3-pyrazolin-5-ones

Pyrazolones show a great variety of reactions with carbonyl compounds (B-76MI40402). For instance, antipyrine is 4-hydroxymethylated by formaldehyde and it also undergoes the Mannich reaction. Tautomerizable 2-pyrazolin-5-ones react with aldehydes to yield compound (324) and with acetone to form 4-isopropylidene derivatives or dimers (Scheme 8 Section 4.02.1.4.10). 

The one-pot three-component reaction of polyethylene glycol-supported acrylate 623 with aldehydes 621 and hydrazines 622 in the presence of chloramine-T followed by methanolysis afforded pyrazolines 624 in good yields and high purities (Scheme 77) <2003SL1467>. 1,3-Dipolar cycloaddition of resin-supported acrylic acid 625 with the nitrilimines generated in situ by oxidation of the aldehyde phenylhydrazones with (diacetoxy)iodobenzene under microwave irradiation gave 626, which was converted into l-phenyl-3-substituted-2-pyrazolinyl-5-carboxylates 627 (Scheme 78) <2004SC3521>. 

Aldehydes and ketones react with azolinones. The reaction between aldehydes and 2-phenyl-5-oxazolinone (131 Y = H), formed in situ from PhC0NHCH2C02H and AC2O, gives azlactones (131 Y = RCH). Similar reactions are given by 4-thiazolidinones, e.g. (132) gives (133) (79AHC(25)83), and 4-imidazolinones. In pyrazolin-5-ones the 4-position is sufficiently activated for condensation to occur with ketones in acidic media (Scheme 8) (66AH06)347). 

Diazoacetaldehyde dimethylacetal (12) has been used as a substitute for diazoacetaldehyde in 1,3-dipolar cycloadditions with l-benzopyran-2(//)-ones (40), styrene, methyl methacrylate, 1-cyanocyclopentene, and methyl cyclohexene-1-carboxylate (41). The resulting A -pyrazolines were readily transformed in two steps into cyclopropanecarbaldehydes [e.g., 13 —> 14 (Scheme 8.4)]. In a similar manner, 3-phenylcyclopropane-l,2-dicarbaldehyde was obtained from the reaction of 12 with dimethyleneketal of cinnamic aldehyde. 

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>. 

Pyrazolin-5-ones having 3- and 4-a-hydroxyalkyl substituents are prepared in a number of ways. Two of these, alkylation of the corresponding 2-pyrazolin-5-one at N-2 and reaction of 3-pyrazolin-5-ones with aliphatic aldehydes, have already been mentioned. The... 

Bis(3-pyrazolin-5-ones) in which the linking chain is not attached to the pyrazolinone nucleus by functional groups are listed in Tables XVI and XVII. Most of these compounds have as the linking chain an arylidene group and are prepared by the reaction of 3-pyrazolin-6-ones with aryl aldehydes,B66 e68,569,807,1001,1133 as shown in eq. 117 (p. 50). Some aliphatic aldehydes have also been used in this reaction.409 3-Pyrazolin-5-ones react with formaldehyde or formamide to form the corresponding bis compounds (eq. 142).910-1192 Under basic conditions... 

Presumably the linking group is >NCH—N<. Bisamides of l-(amino-phenyl)-2-pyrazolin-5-ones and of 3-amino-2-pyrazolin-5-ones have been used. l-(3-Aminophenyl)-3-methyl-2-pyrazolin-5-one reacts with many aldehydes and ketones to form polymers.964 Probably condensation occurs at C-4 and the amino group. The product of reaction of p-cresol with formaldehyde has been found to react with 1-(4-hydroxy -phenyl)-3-methyl-2-pyTazolin-5-one to give a polymer that must have the aromatic and pyrazolinone rings connected by ether linkages.1269... 

The reactions undergone by 5-imino-3-pyrazolidinones are in general very similar to those of 2-pyrazolin-5-ones. The hydrogen atoms at C-4 are active and this position is the reactive center in the nucleus of these molecules. Condensation with aldehydes and ketones occurs with formation of benzylidene644,1083 or 4,4 -benzylidenebis... 

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