3- Pyrazolin-5-ones reduction

Only two topics are of importance for this section the reduction of pyrazolium salts and 3-pyrazolin-5-ones by complex hydrides, and the nucleophilic photosubstitution of pyrazoles and indazoles. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

Reduction of one or two double bonds in the azole ring gives nonaromatic systems. Historically, these derivatives have been described as azolines and azolidines, as illustrated by the pyrazole derivatives 25 and 26. In 3-pyrazoline 25 the 3 indicates the first ring atom associated with the double bond . In the older literature the position of the double bond is indicated by An, where n is the number of the first ring atom associated with the double bond, e.g., A3-pyrazoline 25. Alternatively, they are named as dihydro or tetrahydro derivatives of the parent azole (e.g., 2,5-dihydropyrazole 25) and this nomenclature is IUPAC-preferred nomenclature for rings with more than two heteroatoms . 

Alphen1513 it is also obtained by the reductive cyclization of a crotonic ester (eq. 56). The replacement of a 4-imino function in a 2-pyrazolin-5-one by a 2-pyrazolin-5-one lacking a 4-substituent also leads to a... 

The 3-pyrazolin-5-one ring is stable to mild catalytic reductions, such as reduction with low pressure hydrogen in the presence of platinum or palladium catalyst.532,860 However, under extremely drastic conditions, hydrogen at a pressure of 1000 atmospheres and a tem-... 

The methylation of 4-arylazo-2-pyrazolin-5-ones has already been mentioned.52 Nitration occurs with replacement of the 4-arylazo group.262 Reduction occurs readily but two different paths are followed. As mentioned earlier, 4-amino-2-pyrazolin-5-ones can be obtained by catalytic reduction670 and with zinc and hydrochloric acid.397 However, reduction with zinc and acetic acid leads to rubazonic acids (eq. 189). 

Most syntheses of tertiary amino-3-pyrazolin-5-ones are based on an alkylation by one means or another of the primary or secondary amino analogs. In some cases simultaneous reduction of a nitroso or nitro compound or of a Schiff base and alkylation of the amine so formed is carried out. 4-Dimethylamino-3-pyrazolin-o-ones (amino-... 

Reduction of 4-nitroso-2,3-dimethyl-l-phenyl-3-pyrazolin-5-one with zinc or iron and acid554,550 915 or catalytically561 in the presence of formaldehyde also gives aminopyrine. The analogous 4-nitro compound can also be reduced catalytically in the presence of formaldehyde... 

Arylazo-3-pyrazolin-5-ones have been used as dyes. They form complexes with chromium which have good dyeing properties.1060 Miehaelis, Kotelmann and Drews984 report the reduction of 4-aryl-azo-3-pyrazolin-5-ones having no 1-substituent to pyrazoles by use of phosphorus pentasulfide (eq. 202). Reaction of such azo compounds... 

The reduction of 4-nitroso-3-pyrazolin-5-ones has already been discussed in connection with the synthesis of 4-dialkylamino-3-pyra-zolin-5-ones. This reduction occurs readily to give the corresponding amine when catalytic hydrogenation or various chemical combina-tions461,092,1174 1175 are used. Oxidation of nitroso to nitro occurs in the presence of excess of nitrous acid or by use of nitric acid.984-992... 

The alkylation of 4-nitro-2-pyrazolin-5-ones at C-4 with diazomethane478 has already been mentioned. This hydrogen atom is also replaceable with bromine.1642 Reduction of the nitro group with stannous chloride forms the corresponding amine.478,480 Picrolonic acid condenses with itself to form a bis(2-pyrazolin-5-one) connected by a double bond at the 4,4 -position, with elimination of two moles of nitrous acid.690 Condensation also occurs in the presence of phenyl-hydrazine, but 4,4 -bis[3-methyl-l-(4-nitrophenyl)-2-pyrazolin-5-one] is formed.690... 

For purposes of classification the 4-aminopyrazoles are considered to be 4-imino-2-pyrazolines and analogs of 2-pyrazolin-4-ones. These compounds are listed in Table XL. Such compounds can be prepared by direct cyclization using ethyl diazoacetate and ethyl cyanoacetate.92 This is the same as eq. 243, except that the malonic ester is replaced by ethyl cyanoacetate. Purines can be hydrolyzed to 4-imino-2-pyrazolines by using strong acid.1210 1846 By far the most frequently used preparation is reduction of appropriately substituted pyrazoles, such as 4-nitro,368,812,819,1015,1019,1049 4-nitroso1165 or 4-aryl-azo.671 974,995 The hydrolysis of the carbethoxy 4-imino-2-pyrazolines derived from ethyl cyanoacetate and ethyl diazoacetate forms 4-imino-2-pyrazolin-3-carboxylic acid which is readily decarboxylated to the parent compound.92... 

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... 

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