Pyrazoline nitration

A -Pyrazolines such as (410) are oxidized by iodine, mercury(II) acetate and trityl chloride to pyrazolium salts (411), and compound (410) even reduces silver nitrate to Ag° (69JOU1480). Electrochemical oxidation of l,3,5-triaryl-2-pyrazolines has been studied in detail (74BSF768, 79CHE115). They Undergo oxidative dimerization and subsequent transformation into the pyrazole derivative (412). 

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. 

The nitration of l,5-diphenyl-3-aryl-2-pyrazolines using potassium nitrate in sulfuric acid has been reported to give the product (31) in quantitative yield (84CHE787). 

With certain compounds, such as pyrazoline carboxylic acids and esters, potassium ferricyanide or silver nitrate has been used,509 and for those compounds unsubstituted on nitrogen, mercuric oxide or acetate.76 Lead dioxide has been successful for the oxidation of 1-alkyl-and 1-arylpyrazolines,9i 76,83 and in certain instances even chromic acid, but not hydrogen peroxide or silver oxide.76 See also L. Smith521 and Birkinshaw et al.b22... 

Many pyrazole-type compounds have been elaborated further. Zirconium(IV) nitrate was found to be a versatile oxidizing agent for the aromatization of 1,3,5-trisubstituted pyrazolines 30 to the corresponding pyrtizoles 31 in acetic acid at ambient temperature <03S1267>. 4-... 

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 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). 

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... 

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... 

Pyrazolin-5-ones form complexes with both inorganic and organic compounds much more readily than do the 2-pyrazolin-5-ones. The most extensive series of complexes is that formed with a variety of metallic salts. Antipyrine (2,3-dimethyl-l-phenyl-3-pyrazolin-5-one) forms a series of complexes with salts of divalent, trivalent and tetra-valent metals. Two molecules of antipyrine form a complex with one molecule of copper, cadmium, cobalt and zinc salts.266,866,1116 Complexes prepared from metallic nitrates are usually hydrated.1322 There also exists a series of complexes in which three molecules of antipyrine form a complex with one or two molecules of metallic salts. Such complexes form with two molecules of simple ferric salts272 or with one of complex iron cyanides.608 Nitrates of thorium, lanthanum, cerium and samarium also give such complexes.841 This ratio also occurs in some antipyrine complexes with cadmium and zinc thiocyanate.266 A number of salts of rare earths and iron which have complex anions such as thiosulfate, thiocyanate, dithionic acid and complex iron cyanides form complexes in which six molecules of antipyrine are present.405,408 608,841,950 Stannic chloride forms salts containing three or four molecules of antipyrine and hydrochloric acid.46... 

Aminopyrine (4-dimethylamino-2,3-dimethyl-l-phenyl-3-pyrazo-lin-5-one) forms complexes similar to those of antipyrine, but usually containing fewer molecules of the 3-pyrazolin-5-one. Complexes with mercury, cadmium, antimony, zinc and cobalt salts include only one molecule of aminopyrine. A number of complexes with cobalt, zinc and calcium salts have two molecules of aminopyrine, some also containing acid and water of hydration.736,1322 The complex with cerous nitrate contains three molecules of aminopyrine.1238 A few other substituted... 

Hurst <93AHC(58)215> has summarized the results of nitration of 1-phenyl-A -pyrazolines for instance, l,5-diphenyl-3-aryl-2-pyrazolines are nitrated by potassium nitrate in sulfuric acid to afford the 1-p-nitrophenyl derivative in quantitative yield. Thermal ring opening of A -pyrazolin-3-carboxylic acids has been used as a method of preparation of )8-aminonitriles <94T7543>, while base-promoted ring opening of 1,1 -disubstituted-3-amino-A -pyrazolinium salts affords either N,N-disubstituted hydrazines or a,)S-unsaturated amidrazones <86SC585>. 

Several interesting reactions of pyrazole or pyrazolines have been noted in the literature. Efficient aromatization of l,3,5-trisubstituted-2-pyrazolines 49 to pyrazoles 50 was achieved under microwave irradiation with silica-gel supported jV-bromosuccinimide and solvent-free conditions or with bismuth(iii) nitrate pentahydrate in acetic acid <0513(65)865, 05SC2581>. 

Copper nitrate on montmorillonite (Claycop) has been used with acetic anhydride to nitrate chlorobenzene in 100% yield, giving 13 85 orthdpara isomers.249 When an iron oxide pillared clay was used, 94% para-isomer was obtained.250 Claycop and its iron analogue have been used to oxidize a pyrazoline to a pyrazole (6.47) in 64-97% yields.251... 

A new acetylene synthesis involves the reaction of 3,4-disubstituted 4-haIo-2-pyrazolin-5-ones with aqueous sodium hydroxide and potassium ferricyanide. The reaction proceeds particularly well for arylacetylenes and is believed to involve the oxidation of an intermediate vinyl radical to a vinyl cation (Scheme 69). A similar reaction mechanism may be involved also in the thallium(iii) nitrate oxidation of pyrazolones prepared from -ketoesters and hydrazine. Full experimental details of this procedure have now been published with yields in the range 68—7-1 % (Scheme 70). 

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