0-Hydroxypyrazoles, synthesis

Synthesis of some pyrazole derivatives from amidoximes was reviewed by Karbonits and Horvath. It has been shown that acrylophenone or methacrylophenone oximes (110) on treatment with BuONO in the presence of pyridine and copper(II) sulfate, and with subsequent interaction with dilute NaOH and acidification, gives 3(5)-phenyl-1-hydroxypyrazole 2-oxide or 4-methyl-3(5)-phenyl-l-hydroxypyrazole 2-oxide (111), respectively (equation 47) ... 

Similar synthesis of l-hydroxypyrazole-2-oxides was realized in the presence of Co(II) ions or HN02 as nitrosating agent. Pyrazole-Af-oxides were successfully obtained from 1,3-dioximes and SOCI2 . 

Synthesis of model systems analogous to histamine led to the pharmacologically interesting aminoethylpyrazoles.32-34 Dimethyl-carbamates and dialkylphosphates of 5-hydroxypyrazoles have been used practically as choline esterase inhibitors.35-41 Such compounds as Isolan (2), Pyrolan (3), and Pyrazoxon (4), which are too toxic for pharmacology, are used as systemic insecticides. There is evidence that 3,5-dimethylpvrazole has a stimulating action on plants.42... 

Sequential functionalization of pyrazole-l-oxides via regioselective metallation led to the synthesis of 3,4,5-trisub-stituted-l-hydroxypyrazoles <2002JOC3904>. 3-Acylated-2-(4-methoxybenzyl)-2//-pyrazole 1-oxides were formed by the reaction between a 3-magnesium 2//-pyrazole-l-oxide and acid chlorides <2002J(P1)428>. 3-Arylated-l-hydroxypyrazoles were synthesized from 3-metallated-pyrazole 1-oxides <2001JOC8654>. The reaction between hexafluorobenzene and the anion of 1-hydroxypyrazole affords a mixture of the products of bis-, tetrakis-, and hexakis-substitution <2004ARK100>. In the case of hexakis(bromomethyl)benzene, its reaction with 1-hydroxy-pyrazole leads to the hexakis-substituted product. 

Concerning the synthesis of iV-hydroxypyrazoles and A -oxides of pyrazole, the authoritative publication of Begtrup <92ACS972> should be consulted. 

The synthesis of pyrazolines and pyrazoles by a [CCNN + C] process has not made significant advances since <84CHEC-I(5)167>. A new method to prepare 1-hydroxypyrazole 2-oxides by nitro-sation of acrylophenone oxime, [CCCN + A] has been reported <93JHCl 163>. 

The reaction of 4,5-diamino-3-hydroxypyrazole (24) with pyruval-dehyde (MeCOCHO) afforded a mixture of compounds 25 and 26 in a ratio of 3 1. This is the only example of a synthesis of this ring system starting from an unsymmetrical dicarbonyl compound. Condensation of the... 

Interest continues to be shown in the photodecomposition of diazonium salts,and aryldiazonium tetrafluoroborates have been recommended as potential photoaffinity labelling reagents for proteins.The key step in a recent synthesis of pyrazofurin involves the photodecomposition of the diazopyrazole (158) to give the hydroxypyrazole (159). ° 2-Azahypoxanthine (160) is the major... 

Schemes 4.4.2 and 4.4.3 show the synthesis of pyrazolynate. 1,3-Dimethyl-5-pyrazolon (9) and 2,4-dichlorobenzoyl chloride (10) react in the presence of calcium hydroxide in isopropanol to give 4-(2,4-dichlorobenzoyl)-l,3-dimethyl-5-hydroxypyrazole (8) [3].

Standard methods involving glycosyl halide or ester derivatives in reaction with protected heterocycles have been applied to the synthesis of various glycosyl derivatives of 5-fluoro-uracil and -cytosine, a number of nitro-imidazoles and -pyrazoles, thiadiazines and oxadiazolo-thiadiazines, and 5-methylthio derivatives of -uracil, -4-thiouracil, and -cytosine,/3-D-ribofuranosyl derivatives of 2-thio-6-azauracil, diethyl 4-hydroxypyrazole-3,5-dicarboxylate, 5-acetyl-uraeil, 2,4- and 2,5-thiazolidinediones, 4-thiomethyl-2-azapurine, 2-hydroxypurine, 3-deaza-adenine-8- C, l-deaza-8-azaguanine, imidazo-(l,2- )l,3,5-triazenes, e.g., (5), //n-benzo-guanosine, -inosine, and -xanthosine (6), and a derivative of lV-2-(i3-D-ribopyranosyl)benzotriazoie. Likewise 2-0-... 

The biselectrophilic reactivity motif of alkynones is also present in 3-substituted alkyl propiolates 2. Utilizing the previously described Michael addition/cyclocondensation approach with various binucleophiles allows the introduction of oxo/hydroxyl substituents to the heterocycle. An example of the concept is the copper(I)-catalyzed carboxylation of terminal alkynes, which allows the convenient synthesis of 3-substituted alkyl propiolates 2 a by trapping the intermediary carboxylate with methyl iodide. This one-pot procedure can be expanded to a three-component process by adding binucleophiles such as amidines 36 and hydrazines 20 to furnish the corresponding 2,6-disubstituted pyrimidin-4(3fl)-ones 54 and 1,5-disubsti-tuted 3-hydroxypyrazoles 55 in a one-pot fashion. The incorporation of nontoxic, abundant and economical carbon dioxide provides an environmentally benign access to interesting heterocyclic structures (Scheme 33) (2014ASC(356)3135). 

Both compound classes can be obtained in moderate to good yields. In the case of 2,6-disubstituted pyrimidin-4(3fl)-ones 54 electroneutral and electron-rich amidine hydrochlorides 36 are favorable as well as electroneutral and electron-deficient terminal alkynes 5. For the synthesis of the 1,5-disubstituted 3-hydroxypyrazoles 55 alkyl-substituted hydrazine hydrochlorides 20 generally provide higher yields. 

Shavnya A, Sakya SM, Munich ML, Rast B, DeMello KL, Jaynes BH (2005) Efficient fluoride-mediated synthesis of 5-alkyl amino- euid ether-substituted pyrazoles. Tetrahedron Lett 46 6887-6891. For the regioselective synthesis of 1-alkyl-5-fluoroalkyl-3-hydroxypyrazoles, see Hamper BC, Kurtzweil ML, Beck JP (1992) Cyclocondensation of alkylhydrazines and p-substituted acetylenic esters Synthesis of 3-hydroxypyrazoles. J Org Chem 57 5680-5686... 

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