3-Chloro-3-pyrazolin-5-ones

These are listed in Table XLVIII. The nitrosation of 3,5-pyrazoIi-dinediones has already been mentioned (Section 2). A second method of preparation of the 4-nitroso-3,5-pyrazolidinediones (which are usually considered to have the tautomeric oximino form) has been used by Michaelis and Kirstein.981 This involves treatment of 3-chloro-3-pyrazolin-5-ones with nitrous acid (eq. 260). A third method of syn-... 

Pyran, tetrahydro-, 3 chloro 2 methyl [2H Pyran, tetrahydro, 3 chloro-2-mcthyl ], cis, trans mixture, 55, 64 2-PYRAZOLIN-5-ONES, 3-alkyl-, 55, 73 2-Pyrazolin 5-one, 3-(l-propyl)-, 55, 73 Pyridine, 2-amino-, p-bromination of, 55, 23... 

The general method for the preparation of diphenylpyrazolines is shown in Scheme 11.8, in which X is a suitable leaving group, usually chloro but sometimes dialkylamino. This reaction normally proceeds readily, although pH control may be important. Preparation of the substituted ketone and hydrazine intermediates needed for the synthesis may involve lengthy and complicated sequences. Further reactions are often required to modify the substitution in ring B after formation of the pyrazoline ring. The preparation of compound 11.26 shown in Scheme 11.9 illustrates one of the simpler instances. 

Although it has not been possible to isolate the diazacyclopentadienone (47), indirect evidence for its involvement in this reaction has been obtained by trapping experiments. When an ether solution of 3,4-diphenyl-4-chloro-2-pyrazolin-5-one was treated with triethylamine in the presence of cyclopentadiene, an excellent yield was obtained of compound (51), which has been shown to be the Diels-Alder adduct. The unlikely possibility that (47) could have the alternative structure in which (51) acts as diene rather than dienophile can be excluded on the basis of the appearance of normal hydrazide carbonyl absorption. 

Reaction of 4-chloro-2-pyrazolin-5-ones with potassium carbonate proceeds along two pathways, leading to diketo derivatives of pyrazoIo[l,2-a]pyrazoIe (syn- and anti- dioxabimanes )- A mechanism involving the intermediate formation of diazacyclopen-tadienone (185) which reacts with its potential extended diazoalkane functionality in dipolar cycloaddition fashion to give syn-dioxabimanes (major product) and anri-dioxabimanes (minor product) has been proposed (Scheme 6) (80JA4983). 

The reaction of 2-pyrazolin-5-ones with phosphorus pentasulfide forms 2-pyrazolin-5-thiones (eq. 44).759 990,1343 The reactants are usually heated at the temperature of boiling xylene. A second method used in the preparation of such compounds is the reaction of 5-chloro-pyrazoles with potassium hydrogen sulfide (eq. 88).977,990,1003... 

The cyclization of a -phenylazo-oc,/9-unsaturated ester with hydrochloric acid has been reported by van Alphen1513-1514 to give a 4-chloro-2-pyrazolin-5-one. 

Malhotra et al. [33] described microwave-induced cyclocondensation of 3,5-diaryl-2-pyrazoline-l-carbaldehyde hydrazones (6) with chloroacetyl chloride to synthesize N-amino-3-chloro-4-(3,5-diaryl-2-pyrazoline-2-yl)-azetidine-2-one (7) (Scheme 4) however, the stereochemical aspect of the p-lactams was not considered. The antimicrobial evaluation of the resultant six p-lactams was performed against Escherichia coli, Proteus mlgaris, Klebsiella pneumoniae, and S. aureus. A few of these p-lactams showed moderate activity. 

SCHEME 4 Synthesis of N-amino-3-chloro-4-(3,5-diaryl-2-pyrazoline-2-yl-)-azetidine-2-ones. 

Bis[p-(dimethylamino)phenyl] hydroxymethyl]-4-chloro-3-methyl-1 -phenyl-2-pyrazolin-5-one, B-00319... 

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