1- Hydroxypyrazole 2-oxides

In the absence of transition metal ions, the initially formed 2-hydroxypyrazole 1-oxide 106 reacts further with HONO to give diaza-pentalene 4,4 -dioxides 75. These can, however, be converted back to the... 

Bromo-3-penten-2-one oxime 111 is converted into 2-hydroxypyrazole 1-oxides 112, when treated first with copper sulfate using pyridine as the solvent and then with butyl nitrite and aq KOH (1994JHC281, 1994JHC1487) (Scheme 34). 

Hydroxypyrazole 1-oxides are chlorinated at C4 using N-chlorosuc-cinimide (NCS) (1980JOC76) to give 4-chloro derivatives 215 (Hal1 = Cl), which can be further chlorinated at C4 using a second equivalent of NCS or f-BuOCl (1980JOC76). 

Iodination of 2-hydroxypyrazole 1-oxides 214 with iodine leads to the 4-iodo-substituted derivatives 215 (Hal = I) (1980JOC76). 

Hydroxypyrazole 1-oxides devoid of 4-substituents 214 were nitrated at the 4-position by HONO or n-butyl nitrite giving rise to the... 

When 2-hydroxypyrazole 1-oxide 106, possessing a substituent at the 4-position, is reacted with acetic anhydride the acetoxy compound 219 is formed and can be isolated (1974JOC2663). Presumably, acetylation of the OH group of 106 is followed by nucleophilic addition of the liberated acetate ions followed by elimination of acetic acid. By heating 219 in diox-ane solution, the acetoxy group migrates to the 4-position giving rise to 220 (Scheme 63). 

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>. 

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 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). 

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). 

N-Hydroxypyrazoles are of interest as acylation and phosphorylation catalysts. Pyrazoles with strongly electron withdrawing groups (pKa < 9) 32 can be oxidized under buffered KHSO5 conditions to provide hydroxypyrazoles 33 in fair to good yields <96MC139>. 

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 . 

The diphenyl derivative 388, R = R = Ph, has an absorption band at 1495 cm S which has been assigned to the carbonyl group. This assignment could be questioned. The following chemical reactions of the compound 388, R = R = Ph, may be noted (a) Raney nickel desulfurization followed by oxidation with manganese dioxide yields dibenzyl ketone,(b) hydrazine yields 3,5-diphenyl-4-hydroxypyrazole (390), (c) phenylhydrazine yields PhCH2COCPh=NNHPh," (d)... 

Dichlorination was also observed when two molar equivalents of NCS or /-butyl hypochlorite reacted with 1-hydroxypyrazoles and their 2-oxides. One equivalent of NCS gave only the 4-monochloro derivative in high yield (80JOC76). When there was already a 4-substituent present, as with 3,4,5-trisubstituted pyrazole 2-oxides or 1-hydroxy-3,4,5-trisubsti-tuted pyrazole 2-oxides, the reaction products were 4-chloro-4// derivatives (77JOC3721). With 2 mol of /-butyl hypochlorite, 3,5-diphenylpyra-zole gave the unstable 1,4-dichloro derivative, which rearranged to form... 

Reaction with one equivalent of iodine transformed 1-hydroxypyrazoles and their 2-oxides into 4-iodo products (80JOC76). The iodative oxidation of pyrazolones has been discussed (87CC711). A 95% yield of 5-iodo-l-(p-tolylsulfonyl)pyrazole was made from the 5-lithium derivative (92PC1). 

Af-Hydroxypyrazoles 38 and their N -oxides 39 are converted by f-BuOCI to the 4-chloro-47/-pyrazoles 40 and 41, respectively25,26,56 (Scheme 14). Unlike Scheme 6, the reaction proceeds even when R1 and R are alkyl. When... 

Reduction of ketone (81) with zinc and acetic acid produced the 4-hydroxypyrazoles (87), whereas reaction with dithionite gave the corresponding 1,4-dihydroxypyrazoles (88). These compounds could be oxidized with Fremy s salt (potassium nitrosodisulfonate) to the 3,4-diazacyclopentadienone 3-oxides. 

Substituted pyrazole 1-oxides 74 can be prepared by N-oxidation of 1-substituted pyrazoles 89, by A/-alkylation of 1 -hydroxypyrazoles 90, or by cyclization of 1,3-oximimines, conjugated oximenamines, or conjugated 1,3-nitrosoimines. 

N-Alkylation of 1-hydroxypyrazoles 90 produces 2-substituted pyrazole 1-oxides 91 (Scheme 26). Competing O-alkylation of the... 

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