3- Pyrazolin-5-ones halogenation

The salicylaldehydes commonly used have nitro, alkoxy, or halogen substituents, and need no further comment. Some unusual ones have cationic substituents 3-, 4- and 5-methylthio- and dimethylaminosalicylaldehydes have been prepared and methylated to the corresponding dimethylsulfonium and trimethylammonium salicylaldehydes. 1012 The salicylaldehyde substituted in the 4-position with a 3,5-diphenyl-2-pyrazolin-l-yl group gives a series of BIPS and spiro(dipyrans) having highly fluorescent spiro forms and nonfluorescent open forms, which is the reverse of the usual situation. 13... 

Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones undergo substitution at C-4 in an aromatic fashion. Halogenation, nitration and coupling with diazonium salts occur readily. In 2-pyrazolin-5-ones such reactions... 

The alkylation of 2-pyrazolin-5-ones at C-4 occurs readily (eq. 31) ii3, i32i wjih compounds having reactive halogen atoms. An example... 

Westoo has reported the synthesis of complex bispyrazolinones which he has called furlones.1608,1610,1611 These have two 2-pyrazolin-5-one rings connected through a dihydrofuran ring which in turn is fused with a pyrazole ring. These were prepared by condensation of 4-halogenated-2-pyrazolin-5-ones, together, with l-aryl-2-pyrazolin-5-ones, or with pyrazole blue (XXII-D) in the presence of a base and copper sulfate (eq. 87). These compounds are listed in Table X. 

The vast majority of reactions undergone by 3-pyrazolin-5-ones occur at the 4-position. These pyrazolinones react by direct substitution, very much as do activated benzene rings. Such reactions as halogenation, nitrosation, sulfonation, acylation, the Mannich reaction and many others give 4-substituted-3-pyrazolin-5-ones. 

The reaction of phosphorus oxychloride with 3-pyrazolin-5-ones is rather similar to the reaction with 2-pyrazolin-5-ones in that oxygen is replaced by halogen. In those cases in which there is no substitution at N-l and aryl substitution occurs at N-2, chloropyrazoles are formed,... 

Iodo- and 4,4-di-iodo-2-pyrazolin-5-ones can be prepared by treatment of 2-pyrazolin-5-ones with iodine-potassium iodide in an alkaline solution.1307 Here, again, either the mono or the dihalogeno product is formed, depending upon the amount of halogen used. 

Extremely good yields have been reported in these halogenations.1605 4-Alkyl-2-pyrazohn-5-ones react with halogens readily, but even with an excess only monohalogenated products have been obtained.1605 Smith and co-workers1309 have found that l,3-dimethyl-2-pyrazolin-5-one reacts with bromine to give both the expected 4-bromo product and also l-bromo-3-methyl-2-pyrazolin-5-one. This same compound was obtained by bromination of 3-methyl-2-pyrazolin-5-one with A-bromo-succinimide.1309 4-Bromo-2-pyrazolin-5-ones have been prepared by bromination of 2-nitroso-3-pyrazolin-5-ones1209 (eq. 205) with... 

Some halogenated 2-pyrazolin-5-ones have been prepared by cyclization of various aliphatic compounds. Darapsky, Berger and Neuhaus353 have treated a /J-hydrazino hydrazide with bromine to achieve cyclization, oxidation and halogenation in one step (eq. 207). 

The 4,4-dichloro-2-pyrazolin-5-ones are reduced with hydriodic acid to the corresponding monochloro compound.1605 The 4-mono-halogenated-2-pyrazolin-5-ones react readily with another mole of the same compound or with unhalogenated 2-pyrazolin-5-ones to give bis(2-pyrazolin-5-ones). In the former case the two rings are linked by a double bond,1307 and in the latter by a single bond.1528... 

Only two halogenated bis(2-pyrazolin-5-ones) have been reported (Table VI). One of these is prepared by bromination of 4,4 -methylidyne-bis(3-methyl-l-phenyl-2-pyrazolin-5-one) with bromine to give the 4-bromo analog.1682 In the second case1109 bromine is added to a diolefinic system connecting two 2-pyrazolin-5-one rings. 

The halogen in these 3-pyrazolin-5-ones is readily replaced with hydrogen by catalytic reduction697,698 or by treatment with acetone.793... 

---