4-Nitro-3-pyrazolin-5-ones

Only a few 4-nitro-2-pyrazolin-5-ones are known. They are listed in Table XXIX. The best-known of these compounds is picrolonic acid, which is 4-nitro-3-methyl-l-(4-nitrophenyl)-2-pyrazolin-5-one. This compound is widely used to form salts of basic compounds for isolation or identification. The hydrogen atom at C-4 is acidic in the 4-nitro-2-pyrazolin-5-ones because of the two adjacent electron-withdrawing groups. This hydrogen is easily replaced by metals when treated with metal alkoxides1642 and reacts with diazomethane.478... 

The usual synthesis of the 4-nitro-2-pyrazolin-5-ones is by nitration of 2-pyrazolin-5-ones under mild conditions (eq. 2 1 4).61-872-690 1004-1683... 

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... 

Of the many substituted and functionalized alkenes that have been combined with diazo dipoles to give A -pyrazolines or products derived from them (i.e., A -pyrazolines, pyrazoles, cyclopropanes), only a selection will be mentioned. These include ot-alkylidene-cycloalkanones (62), -flavanones, -thioflavanones, -chroma-nones, and thiochromanones (63,64) a-arylidene-indanones and -indolones (65) diarylideneacetones (66) l-benzopyran-2(77)-ones (coumarins) (67,68) 4-nitro-1,2-oxazoles (69) 2-alkylidene-2-cyanoacetates (70) dimethyl 2,3-dicyanofuma-rate (71) tetracyanoethylene (72) tetraethyl ethylenetetracarboxylate (72) 1,4-quinones (35,73-75) 2-X-l,l,l-trifluoro-2-propene [X = Br, (76), SPh, SOPh, S02Ph (77)] nitroalkenes (78) including sugar nitroalkenes (79) 1-diethoxyphos-phoryl-1-alkenyl-sulfoxides (80) methyl 2-(acetylamino)cinnamate and -acrylate... 

The results of Katritzky and co-workers [74JCS(P2)382], who carried out an extended study of such systems, are shown in Fig. 10. These indicate that all six compounds studied reacted as the conjugate acid at high acidity. Three compounds also reacted as the conjugate acid at low acidity [3-methyl-4-nitro-l-phenylpyrazolin-5-one, 3-methyl-5-methoxy-4-nitro-l-phenyl pyrazole, and 3-methyl-5-methoxy-l-(4-nitrophenyl) pyr-azole]. The other three compounds [2,3-dimethyl-4-nitro-l-phenylpyraz-olin-5-one, 3-methyl-1-(4-nitrophenyl) pyrazolin-5-one, and 2,3-dimethyl-1-(4-nitrophenyl) pyrazolin-5-one] reacted as free bases at low acidity. 

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... 

The development of new and improved dyes based on pyrazolinone structures has likewise led to modem developments of no inconsiderable magnitude. The use of tartrazine as an approved color for foodstuffs is of significance. The development of pyrazolinone dyes for use as magenta couplers and sensitizers in color photography and in metal chelate dye structures has established a renewed, modem interest in these dyes. The chelating characteristics, which will be of continuing theoretical structure interest in coordination chemistry, have been used in developing picrolonates (salts of 3-methyl-4-nitro-l-p-nitrophenyl-2-pyrazolin-5-one) of possible utility in analytical procedures. 

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. 

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... 

Knorr 809 first prepared 4-oximino-2-pyrazolin-5-ones by treatment of 2-pyrazolin-5-ones with nitrous acid (eq. 208) and this has remained the standard method of preparation.25,413,446 818 1004,1549 If an excess of nitrous acid is used, the nitroso substituent introduced is oxidized further to a nitro substituent.992 Amyl nitrite9 and nitrogen trioxide355,406 have also been used as nitrosating agents, though not extensively. 

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... 

Two 4-nitro-5-imino-2-pyrazolines are listed in Table XII. One of these was prepared by permanganate oxidation of the 4-oximino compound1010 and the other by direct nitration.1656 These compounds were believed to be aminopyrazoles rather than 5-imino-2-pyrazolines. 

The 4-nitro-3-pyrazolin-5-ones are listed in Table XXVIII. They have been prepared most frequently by direct nitration of 3-pyrazolin-5-ones, usually with concentrated nitric acid.807,809,880,888,1001,1320 The oxidation of 4-nitroso-3-pyrazolin-5-ones to give the 4-nitro compounds has been mentioned in connection with reactions of the 4-nitroso compounds. Nitration of 3-pyrazolin-5-ones with nitrogen tetroxide has been accomplished.1491... 

The nitro group of 4-nitro-3-pyrazolin-5-ones is readily reduced to an amino group by metal-acid combinations.984,1001... 

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... 

Only half-a-dozen of these compounds are known (Table XLI) and at least this number of methods of preparing them have been reported. Borsche and Manteuffel125 have found that 2-pyrazolin-4,5-diones are formed as the by-products when oc-ketoesters are treated with aryl-diazonium salts. The principal products are 4-arylazo-2-pyrazolin-5-ones. Nitric acid oxidation of 3-methyl-l-phenyl-2-pyrazolin-5-one forms the corresponding 4,5-dione.809 Wislicenus and Gtiz1842 heated 4 -bromo - 4 - nitro -1 - (4 - bromophenyl) - 3 - methyl - 2 -pyrazolin - 5 - one in water and obtained the analogous 4-oxo compound. Acid hydrolysis of rubazonic acids, which are 4-imino-2-pyrazolin-5-ones, leads to 2-pyrazolin-4,5-diones.424 809 Oxidation of 4,4 -bis(2-pyrazolin-5-ones) or of rubazonic acids with nitric acid809 forms the 4,5-diones. 

TABLE XXVIII. 3-Pyrazolin-5-ones. Nitroso and Nitro Substituted Derivatives... 

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