Pyrazoline sulfonation

Sulfonation of 2- and 3-pyrazolin-5-ones occurs at position 4. Thus 3-methyl-1-phenyl-pyrazolin-5-one with 20% oleum at 10-15 °C yields the corresponding 4-sulfonic acid (304) (64HC(20)l). Higher temperatures cause sulfonation not only of the heterocycle but also of the phenyl group. Antipyrine treated with sulfuric acid and acetic anhydride yields (305). 

The equilibrium in pyrazolin-5-ones, containing one or more carboxylate or sulfonate group, is extremely sensitive to the pH of the medium. For example, pyrazolinone 105c, which exists in D2O solution at pH 2 as an enol... 

In the presence of base, the sulfone 189 rearranges to the methylene-pyrazoline 190, whereas its regioisomer 191 shows no reaction (Scheme 65).57 This is the reverse of the type of thermal rearrangement shown in Scheme 25. 

The features of the electronic structure of aryl-substituted pyrazolines influence their chemical properties. For example, in the case of 3-substituted 7V-phenyl-pyrazolines 100 reactions of formylation, acylation, nitration, sulfonation, azocoupling and other electrophilic processes involve the para position of the 7V-phenyl ring, with formation of compounds 101 [103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113]. On the other hand, some electrophilic reactions, including nitration, bromination, chlorination, formylation and azocoupling, for 3-unsubstituted pyrazolines 102 occur at position 3, yielding heterocycles 103 and in some cases as a mixture with 104 [108, 114, 115] (Scheme 2.26). This fact provides evidence for orbital control of these reactions. 

Pyrazoline-3- or -5-carboxylic acids, their derivatives, and the derivatives of the corresponding sulfonic acids are oxidized by bromine to the corresponding pyrazoles in yields of 50-75%. 4,15S-402-484-506... 

Amino polystyrene pyrazolone linker resin 58 provided various amide products 59 with a high conversion rate and good purity under mild conditions the resin linker was stable under the reaction conditions, resistant to hydrolysis, and reused repeatedly without loss of activity <03TL8063>. The preparation of pyrazoline derivatives 61 was accomplished with traceless solid-phase sulfone linker 60 with phenylhydrazine <030L1067>. Aniline cellulose-bound enaminones 62 reacted with phenylhydrazine under microwave irradiation to produce pyrazolocarboxylic acid derivatives 63 in high yields <03JCO465>. 

The preparation of pyrazoline derivatives 595 was accomplished by reaction of phenylhydrazine with a traceless solid-phase sulfone linker 594 (Equation 121) <20030L1067>. 

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 only compounds of this kind which have been reported are 5-oxo-2-pyrazolin-4-sulfonic acids (Table XXXV). They are prepared by direct sulfonation, usually with fuming sulfuric acid.684,885,1671, 1672,1674 Sulfonation occurs at temperatures as low as 10-15°,684 but it takes place much more rapidly at higher temperatures. If an aryl... 

Oxo-3-pyrazolin-4-sulfonic acids (Table XXXVI) are prepared by direct sulfonation738,745 with sulfuric acid and acetic anhydride or by chlorosulfonation with chlorosulfonic acid, followed by hydrolysis to the acid.1248,1249 The reaction of 2,3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-sulfonyl chloride with urea forms a bis(5-oxo-2-pyrazolin-4-sulfonic acid) derivative,1249 the only such bis derivative reported. Reduction of the sulfonic acid chlorides with zinc and acid forms the corresponding mercapto compound.1249... 

Dimethyl-2-phenyl-3,4-pyrazolidinedione and its 1,5-diphenyI-2-methyl analog are the only compounds of their class known. The former has been synthesized by treatment of l-(2,3-dioxobutyryl)-l-phenyl-2-methyl-2-nitrosohydrazine hydrate with sodium bisulfite" and by methylation of 4-hydroxy-3-methyl-l-phenyl-2-pyrazolin-5-one.820 The latter compound has been prepared in the same way.1243 The dimethyl phenyl compound has also been isolated from urine as a metabolic product of 4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyra-zolin-5-one617 and it is formed by treatment of the same compound with sulfuric acid.618 The 4-thiono analog is also known. Reduction of 2-3-dimethyl-l-phenyl-5-oxo-3-pyrazolin-4-sulfonic acid using zinc in acid gives l,5-dimethyl-2-phenyl-4-thiono-3-pyrazolidinone.1249... 

TABLE XXXV. 2-Pyrazolin-5-ones. Sulfonic Acids ... 

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