3- Hydroxypyrazoles

B = phenyl, pyridinyl, cyclohexene, or cyclopentene A = biaryl, tricyclic, bicyclic. 

ArB(OH)2 (Sequiv), K3PO4 (3equiv) PdCyOPPF) (8 mol%), DPPF(4mol%) 1,4-dioxane, 100 °C 71-92% 

An electrochemical study related to the electrooxidation of the 3-hydroxy and 3-methyl derivatives of l-phenyl-4-butyldithiocarboxylato-5-hydroxypyrazole in aqueous ethanol solutions covering a wide pH interval was performed 2000JEC46 . 

The most important contribution to pyrazolinone tautomerism is the inclusion of solvent elfects on the theoretical calculations 90JCS(P2)195, 93JA2352). Theoretical calculations of the relative stabilities of the four tautomers of pyrazolinone (3-hydroxypyrazole A (OH form), 3-pyrazolin-5-one B (NH form), 5-hydroxypyrazole C (OH-form), and 2-pyrazolin-5-one D (CH form)) have been considered a challenge to theory 93JA2352 theory predicts the order D A C B in the gas phase, which is different from the experimental results in solution 84CHEC-I(5)167 . 

Boulton 86JCS(P1)1249 has described the synthesis of 3-methoxyindazole from indazolinone and Aran 93JCS(P1)1119 has reported the transformation of sp/ro-indazolylio oxides into dimeric macrocycles (l-alkyl-3-alkyloxy-bisindazoles). 

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Azidopyridazine 2-oxides give on thermolysis either maleonitrile (19), /3-cyanoacrylate (20) or 2-cyano-l-hydroxypyrazole (21), dependent on the substituent at the 6-position (Scheme 4) <75CC703>. 

Diazo coupling is expected to occur only with highly reactive systems, and experiment bears this out. Diazonium ions couple with the anions of N-unsubstituted imidazoles at the 2-position (e.g. 125 yields 126) and with indazoles (127) in the 3-position. In general, other azoles react only when they contain an amino, hydroxyl, or potential hydroxyl group, e.g. the 4-hydroxypyrazole (128), the triazolinone (129) and the thiazolidinedione (130) (all these reactions occur on the corresponding anions). 

Sometimes compounds which exist predominantly in the hydroxyl form give products of N-methylation with diazomethane, for example 3-hydroxy-5-phenylisothiazole (63AHCi2)245) of course, the ambident anion (493) is an intermediate. 3-Hydroxypyrazoles, under rather severe conditions, can be converted into 3-chloropyrazoles with POCI3 <66AHQ6)347). 

The hydroxyl groups of 5-hydroxypyrazoles (498) are readily replaced by halogens by the action of phosphorus halides. 

NH form e.g. 505). Most 4- and 5-hydroxy compounds of types (500) and (502) exist largely in these non-aromatic azolinone forms, although the hydroxyl form can be stabilized by chelation e.g. 506). The derived ambident anions react with electrophiles at O or C. Replacement of the hydroxyl group is sometimes possible provided electron-withdrawing groups are present as, for example, in 5-substituted 4-hydroxypyrazoles. 

V-Hydroxy groups can be acetylated (AC2O) and O-alkylated in basic media by methyl iodide. 1-Hydroxypyrazole 2-oxides are quite strong acids. 

The problem of tautomerism is simpler in the case of 1-substituted pyrazolin-3-ones since only two forms, the OH (140a) and the NH (140b), are possible. The OH form is the more stable and is the only one present in the crystal (Section 4.04.1.3.1). In protic solvents, like water or methanol, the equilibrium position is much more evenly balanced between the OH and NH forms. Finally, 4-hydroxypyrazoles (141) exist as such. A CNDO/2 calculation justifies the result that 4-hydroxy tautomers are relatively more stable than... 

The 1-hydroxypyrazoles exist as the neutral structure (151a) and not in the iV-oxide form (151b), although in water there is a small percentage of the latter present. For tautomerism of 2-hydroxyindazole see (82JOC4323). 

In the case of 4-hydroxypyrazole, tautomer (159), although not abundant in the equilibrium mixture (Section 4.04.1.5.2), must be considered when discussing their reactivity. 

Photooxidation has also been used to transform pyrazolines into pyrazoles (74AJC2267) and 3-pyrazolidones into 3-hydroxypyrazoles (76CC685). 

From the results quoted in Section 4.04.2.1.3(x) the stability of acetyl derivatives of indazolone decreases in the order Af(l)-acetyl >A (2)-acetyl > 0(3)-acetyl. The reactivity of 3-hydroxypyrazoles is covered by Dorn s comprehensive review (80CHE1). Amongst the results reported there are the Claisen rearrangement of allyloxypyrazoles (475a) (475b)... 

The title compounds also undergo the Claisen rarrangement (5-allyloxypyrazoles 4-allyl-5-pyrazolones) and are readily transformed into 5-chloropyrazoles by means of phosphorus oxychloride (8OCHE1). In the presence of aluminum chloride 5-acyloxypyrazoles (481) undergo the Fries rearrangement affording 4-acyl-5-hydroxypyrazoles (482). 

Hydroxypyrazoles are amphoteric compounds which form salts with alkalies and with mineral acids (B-76MI40402). The 4-hydroxy group directs electrophilic substitution towards... 

The iV-hydroxypyrazoles (523 R = H) and the pyrazole iV-oxides (268 Section 4.04.2.1.3 (xiii)) have been reduced to pyrazoles by means of zinc in acetic acid and catalytic hydrogenation, respectively (75MI40402). 

Pigments derived from pyrazolones include Hansa Yellow R, l-phenyl-3-methyl-4-[(2,5-dichlorophenyl)azo]-5-hydroxypyrazole and Pigment Chrome Yellow, 1-phenyl-3-methyl-4-[(o-tolylazo]-5-hydroxypyrazole, as examples of monoazo compounds. 

Analytical applications of pyrazolones have been reviewed by Busev et al. (65RCR237). Organic bases are easily characterized by formation of highly crystalline salts with picrolonic acid (l-(4-nitrophenyl-3-methyl-4-nitro-5-hydroxypyrazole). The last-named compound is used as a reagent for alkaloids, tryptophan, phenylalanine and for the detection and estimation of calcium (B-76MI40404). 

Pontacyl Light Yellow GX [Acid Yellow 17, l-(2,5-dichloro-4-sulfophenyl]-3-methyl-4-(4-sulfophenylazo)-5-hydroxypyrazole di-Na Salt] [6359-98-4] M 551.3, Cl 18965, Xmax... 

Tlie major tautomer of 3-hydroxypyrazol-5-one is the dioxo form 215a, but in pyridine 215a exists in equilibrium with 215b (Scheme 72) [76AHC (SI), p. 450],... 

The chelated tautomeric forms shown are prepared for 4-ethoxycar-bonyl-l,2,3-thiadiazC le-5-one 250 and 3,5-dibenzoyl-4-hydroxypyrazole 251 [76AHC(S1), pp. 359,384]. 

Examples of the fixation of very minor prototropic tautomeric forms on complexation are known in the series of complexes of l-(2 -pyridyl)-5-hydroxypyrazoles 383 [76AHC(S1), p. 333 70ZOB1114] and 2-[2 -hydroxy (A-tosylaminophenyl)]benzazoles 385 (Scheme 142) (98ZOB496). 

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