Pyrazolidin-3-ones

A variety of mono- and bi-cyclic /3-lactams have also been prepared by oxidative ring contraction of pyrrolidine-2,3-diones (180) (75JOC2356), and by the photolysis of pyrazolidin-3-ones (181) (78T1731, 75JOC3510, 75JOC3502, 75CC725). 

Aziridinium ion-based click chemistry provides convenient access to pyrazolo[l,2-ajpyrazoles, active inhibitors of penicillin-binding proteins [58, 59]. Ring-opening of aziridinium ions 32 at the benzylic position with hydrazine, followed by intramolecular cyclization, gave pyrazolidin-3-ones 37 in excellent yields (Scheme 12.27). Heating of the hydrazides 37 with aromatic aldehydes at reflux in absolute... 

Synthesis of isomeric chiral protected (63 )-6-amino-hexahydro-2,7-dioxopyrazolo[l,2- ]pyrazole-l-carboxylic acid 280 is shown in Scheme 36. Crude vinyl phosphonate 275, obtained by treatment of diethyl allyloxycarbonylmethyl-phosphonate with acetic anhydride and tetramethyl diaminomethane as a formaldehyde equivalent, was used in the Michael addition to chiral 4-(f-butoxycarbonylamino)pyrazolidin-3-one 272. The Michael addition is run in dichloro-methane followed by addition of f-butyl oxalyl chloride and 2 equiv of Huning s base in the same pot to provide 276 in 58% yield. The allyl ester is deprotected using palladium catalysis to give the corresponding acid 277, which is... 

The 3-oxo-2-pyrazolidinium ylides 315, easily available by reaction of the corresponding pyrazolidin-3-one with aromatic aldehydes, function as 1,3-dipoles in cycloaddition reactions with suitable alkenes and alkynes to provide the corresponding products. When unsymmetrical alkynes are used, mixtures of both possible products 316 and 317 are usually obtained (Equation 45). The regioselectivity of cycloadditions of the reaction with methyl propiolate is influenced by the substituents on the aryl residue using several 2,6-di- and 2,4,6-trisubstituted phenyl derivatives only compound 316 is formed <2001HCA146>. Analogous reactions of 3-thioxo-l,2-pyrazolidinium ylides have also been described <1994H(38)2171>. 

Pyrazolopyrazoloquinoline derivatives can be prepared by treatment of pyrazolidin-3-one with 2-chloroquinoline-3-carbaldehyde, which gives firstly the zwitterionic compound 283. Reduction with sodium borohydride followed by ring closure in basic media gives the fused tricyclic heterocycles (Scheme 77) <1991T9599>. 

Proline-based palladium complex 106 has been shown to catalyze the Diels-Alder reaction of 1,2-dihydropyridine 85 and oxazolidinone 99 to give 103 in similar enantiomeric excess as the chromium(m) complex 102<2005TL5677>. Alteration of the dienophile to pyrazolidin-3-one 107 improves the enantioselectivity of the reaction and gives product 108 in 97% ee (Scheme 29). 

Pyrazol-5-ones are widely used in medicine, color photography, analytical chemistry, and agriculture. The tautomeric equilibria between the CFI, OH, and NH forms in a series of 4-substituted-l-phenyl-3-methyl-pyrazolin-5-ones 100-102 have been studied using ab initio calculations at various levels of theory and comparison made with the experimental results obtained from C NMR measurements <2001JP0566>. The tautomerism of 4-acyl-2-phenyl-2-pyrazolidin-3-ones 103 and 104 was studied by C NMR spectroscopy <1999CHE748>. The tautomerism of... 

Stereoselective Diels-Alder reactions have been reported in several cases. Enantioselective Diels-Alder reactions of l-phenoxycarbonyl-l,2-dihydropyridine with 1-alkylated acryloyl-pyrazolidin-3-ones using a chiral cationic palla-dium-phophinooxazolidine catalyst afforded chiral isoquinuclidines with excellent enantioselectivity <2005TL5677>. Bismuth(lll) chloride-mediated diasteroselective intramolecular [4-f2] cycloaddition reactions of A-allyl derivatives of pyrazole aldehydes led to fused sulfur-containing pyrazole heterocycles <2003SC3063>. A highly diastereoselective intramolecular hetero-Diels-Alder approach toward tetracyclic pyrazoles from 5-(3-methyl-2-butenylthio)-3-methyl-l-phenyl-4-pyrazolecarboxaldehyde has been reported <1997SL1155>. 

The enantioselective Diels-Alder cyclization of N-phenoxycarbonyl-1,2-dihydropyridine 129 with 1-alkylated acryloyl-pyrazolidin-3-ones (130) using chiral... 

Low yields of bicyclic bimanes are formed by treatment of pyrazolidin-3-ones with acetoacetates <80JA4983>. Much better yields are obtained with acetoacetates substituted at the position 2 with electron attracting substituents, for instance ester or acyl groups. a //-Isomers (337) are predominant products, 5yn-isomers (338) and pyrazolo[5,l-b][l,3]oxazines (339) are minor products (Equation (48)) <84CPB930>. 

Diaza-compounds. The pyrrolo-pyrazole derivative (705) is one of the products of the action of acids on the tosylhydrazone H2C=CMe(CH2)2CH=N—NHTos. The reaction of 2,5,5-trimethyl-l-pyr-roline iV-oxide (706) with the ketenimine Ph2C=C=NPh yields the pyrrolo-imidazole (707)/ Pyrazolidin-3-one and 3-chloropropanoyl chloride combine to form the dioxopyrazolopyrazole (708)/ Irradiation of l-(o-iodoben-zoyl)imidazole (709 R=H) produces the indolobenzimidazolinone (710) the... 

Photochemical ring contraction of the pyrazolidin-3-one (68) (93BMC2383) and the pyridone (70) (93CPB1885) gives the lactams (69) and (71) respectively. 

Pyrazoline heterocycles and specially dihydropyrazolones are widely used as dyes for various applications in food, textile, photography and cosmetics industries. Some of these heterocycles exhibit useful biological properties, and for example, phenazone was one of the first synthetic drugs. The corresponding saturated pyrazolidin-3-ones exhibit similar properties, as exemplified with the anti-inflammatory drug phenylbutazone. Moreover, this heterogeneous copper(I)-modified zeolite catalyst can be reused six times without significant loss of activity. 

Several oxo compounds are derived from pyrazolidine, a cyclic N,N -disubstituted hydrazine. Pyrazolidin-3-ones as well as pyrazolidin-4-ones are known [459]. The anti-inflammatory phenylbutazone (1) is a substituted pyrazolidine-3,5-dione. It is prepared by C-alkylation of l,2-diphenylpyrazolidin-3,5-dione. For the industrial synthesis, cyclocondensation of 1,2-diphenylhydrazine with diethyl 2-butylmalonate is preferred ... 

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