2- Pyrazolin-5-ones oxidation

A-Oxidation with peracids (Section 4.04.2.1.3) and the transformation of pyrazoles into 4,4-dihalogeno-2-pyrazolin-5-ones (Section 4.04.2.1.4(v)) have already been discussed. Transformation of non-aromatic 2-pyrazolin-5-ones into the 4-oxo derivatives will be examined in Section 4.04.2.2.l(ii). 

The recently reported (757) conversion of 5-pyrazolones directly to a,j8-acetylenic esters by treatment with TTN in methanol appears to be an example of thallation of a heterocyclic enamine the suggested mechanism involves initial electrophilic thallation of the 3-pyrazolin-5-one tautomer of the 5-pyrazolone to give an intermediate organothallium compound which undergoes a subsequent oxidation by a second equivalent of TTN to give a diazacyclopentadienone. Solvolysis by methanol, with concomitant elimination of nitrogen and thallium(I), yields the a,)S-acetylenic ester in excellent (78-95%) yield (Scheme 35). Since 5-pyrazolones may be prepared in quantitative yield by the reaction of /3-keto esters with hydrazine (168), this conversion represents in a formal sense the dehydration of /3-keto esters. In fact, the direct conversion of /3-keto esters to a,jS-acetylenic esters without isolation of the intermediate 5-pyrazolones can be achieved by treatment in methanol solution first with hydrazine and then with TTN. 

Aroylhydrazines are readily oxidised in protic solvents. Benzoylhydrazine and 2-benzoylphenylhydrazine show anodic waves in an acetate buffer at +0.08 and +0.02 V vs. see respectively [147], The most studied member of this group, because of its importance as the photographic developer phenidone, is 1-phenyl-pyrazolin-3-one 33. Phenidone shows a one-electron oxidation wave at a rotating... 

Oxidation of ketone phenylhydrazones generates a radical-cation centre on the nitrogen atom adjacent to the benzene ring. The radical-cation is delocalised by both the hydrazone group and the phenyl ring. Reactions of 1,3,5-triphenyl-A -pyazolines illustrate the properties of these radical-cations. Two one-electron waves are seen at a rotating disc electrode in acetonitrile and for 1,3.5-triphenyl-pyrazoline, Ey. = 0.82 and 1.68 V vs. see [33]. The delocalised radical-cation is... 

The electrochemical oxidation of 4-dimethylaminoantipyrine (4-dimethyl-amino-2,3-dimethyl-l-phenyl-A3-pyrazolin-5-one) has been investigated in CH3CN-NaC104 at a glassy carbon electrode.421 The first step is a quasi-reversible electron transfer from the lone-pair electrons on the 4-dimethyl-amino nitrogen to form the radical-cation. The second-order disappearance of the radical-cation is presumably due to a disproportionation reaction. The oxidation at the potential of the plateau of the first wave gave the protonated 4-dimethylaminoantipyrine in 60% yield, but other products were not identified. 

It is evident that the pyrazol-3-one ring system is less reactive than other m-azadienophiles. This is attributed to the fact that the azo linkage in (47) is not so electron poor as those in (53) and (54). The degree of substitution in the pyrazoline ring does not appear to hinder the oxidation,... 

The reaction has proceeded satisfactorily with one or two benzoyl groups present,153,507 but a benzoyl group in position 1 has also been eliminated.153 The oxidation proceeds similarly when position 4 is substituted.608 Pyrazoline itself and monoalkyl- and monoaryl-pyrazolines give the corresponding pyrazoles only in small yield on oxidation with bromine.509,510 In the majority of cases bromination occurs together with oxidation, and often brominated products are the only ones isolated. Thus 1,3,5-triphenylpyrazoline yields a tribromide of unknown constitution.49 The hydro bromide of 4-bromopyrazole (43) was obtained almost quantitatively from 3-butoxy-J1-pyrazoline (42).611A mixture of 1,5-dimethylpyrazole and the 4-bromo compound... 

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>. 

L-f/ireo-glycerol-l-yl)-pyrazoline-5-one (49) when its solution in alkali was acidified with acetic acid (50). The reaction was further extended to other bis(arylhydrazones) (51), The structure of the phenyl analogue (49) was established by oxidation to the known 3-carboxy-l-phenyl-4-phenylazopyrazolin-5-one (50). Later, on the basis of NMR data (39), the structure of this group of compounds was formulated as the hydra-zones (51). Acylation of 51 aflForded the tri-O-acylated derivatives (51), while periodate oxidation of 51 gave 3-formyl-l-aryl-4,5-pyrazoledione-... 

The hydrogen atoms on C-4 of 2-pyrazolin-5-ones are readily attacked by mild oxidizing agents. The products of this reaction are bispyrazolinones (eq, 45) when such oxidizing agents as phenyl... 

The most widely used synthesis of 4,4 -bis(2-pyrazolin-5-ones) is mild oxidation of monocyclic 2-pyrazolin-5-ones, which has already been discussed in the section devoted to reactions of 2-pyrazolin-5-ones (eq. 45). These compounds can also be synthesized by reaction of a,a -diacylsuccinic esters with hydrazines (eq. 54).357.807.8i5 a number... 

Only a very few 4,4 -bis(2-pyrazolin-5-ones) linked by a double bond have been prepared. The parent compound of this series, 4-(3-methyl -1 -phenyl - 5 - oxo - 2 - pyrazolin - 4-ylidene)-3-methyl-l-phenyl-2-pyrazolin-5-one (XXII-D), is known as pyrazole blue.323,807,809,816, 1090,1091 was so nameci by Knorr because of its great resemblance to indigo blue. All these compounds are strongly colored. The usual synthesis is by ferric chloride oxidation of monomeric 2-pyrazolin-5-ones (eq. 61)296,809 or by oxidation of the corresponding bis compounds... 

Pyrazolin-5-ones react with concentrated nitric acid809,880,888, 992.1001 or an excess of nitrous acid984,992,1001 to form 4-nitro-3-pyxazolin-5-ones. Presumably the excess of nitrous acid first nitrosates and this product is oxidized to the nitro compound. 

The most widely used and certainly most general procedure for preparation of 4-hydroxy-2-pyrazolin-5-ones is that developed by Veibel, Linholt and Westoo.1525-1528 Usually oxidations of 2-pyrazolin-5-ones lead to formation of bispyrazolinones. These workers found that oxidation of l-substituted-2-pyrazolin-5-ones in alkaline solutions gave very good yields of the 4-hydroxy analogs (eq. 158). Oxidizing agents... 

A number of 4-arylmercapto-2-pyrazolin-5-ones have been prepared by reaction of a 2-pyrazolin-5-one with aryl mercaptans (eq. 163).27,28 It was concluded that the first reaction was oxidation of the... 

A few 4,4 -bis(2-pyrazolin-5-ones) in which the rings are linked by sulfur atoms are known. The linking group is almost always disulfide and is prepared by oxidation of 2-pyrazolin-5-ones substituted in the 4-position with mercaptoaryl groups.578 These compounds are listed in Table VII. 

The 4-amino-2-pyrazolin-5-ones react as do other amines. They can be alkylated with alkyl halides992 and react with aldehydes to form Schiff bases.633"2 Oxidation of these amino compounds with ferric chloride leads to the rubazonic acids (eq. 178) in which two 2-pyrazolin-... 

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