1 3,5-Dimethylpyrazole

3 5-Dimethylpyrazole (III) may be prepared from acetylacetone (I) and hydrazine (II) (produced from hydrazine sulphate and aqueous alkali). The reaction may be represented as  

Dissolve 65 g. of hydrazine sulphate in 400 ml. of 2 5. V sodium liyd i oxide solution contained in a 1-htre three-necked flask, equipped with a thermometer, mechanical stirrer and dropping funnel. Immerse the flask in an ice bath and when the temperature reaches 15° (some sodium sulphate 

Submitted by Richard H. Wiley and Peter E. Hexner.1 Checked by William S. Johnson and Robert J. Highet. 

The yield after drying in a vacuum desiccator containing paraffin chips is 35-37 g. (73-77%) (Note 5). 

Hydrazine sulfate supplied by the Eastman Kodak Company is satisfactory, or it may be prepared by a previously described procedure.2 

A precipitate of sodium sulfate may form at this point. 

Union Carbide and Carbon Corporation technical 2,4-pen-tanedione was used without purification. 

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Another example is a claim of possible industrial appHcation for preparing l-cyclohexyl-3,5-dimethylpyrazole [79580-49-7] (75) and similar compounds from 1,2,6-thiadiazine-l,1-dioxide (74) by extmsion of SO2 (eq. 20) (48). This process has the added advantage of not requiring hydrazine derivatives as reactants. 

Under alkaline conditions, alkyl nitrites nitrosate imidazoles which possess a free NH group in the 4-position (70AHC(12)103). Nitrosation of 3,5-dimethylpyrazole gives the 4-diazonium salt by further reaction of the nitroso compound with more NO". 5-Pyrazolinones are often nitrosated readily at the 4-position. 3-Alkyl-5-acetamidoisothiazoles undergo 4-nitrosation. 

Although the thermodynamic aspects of acylotropy are well documented, there have been few kinetic studies of the process. The activation barrier is much higher than for prototropy and only Castells et al. (72CC709) have succeeded in observing a coalescence phenomenon in H NMR spectra. At 215 °C in 1-chloronaphthalene the methyl groups of N-phenyl-3,5-dimethylpyrazole-l-carboxamide coalesce. The mechanism of dissociation-combination explains the reversible evolution of the spectra (Scheme 9). 

In a mixture of ether and tetrahydrofuran.In HMPT the same barrier is obtained for the 3,5-dimethylpyrazole. Tn DMSO. Pr TPP = tetrakis(p-isopropylphenyl)porphinate dianion. 

Niai) Dimethylbis(3,5 -dimethylpyrazol-1 -yl)gallate [GaMe2(DMPz)2] Complicated structure 80CJC1091 s... 

Cuai) l-Carboxamido-3,5-dimethylpyrazole (CDMPz) Cu(CDMPz)2 (220) 79JCS(D)1867 ... 

Mo(II) Methylbis(3,5-dimethylpyrazol-l-yl)hydroxygallate [GaMe(OH)(DMPz)2] Mo(CO)2(r) AC4H7) [GaMe(OH)(DMPz)2] 79CJC139 ... 

Mo(V) Hydrotris(3,5-dimethylpyrazol-l-yl)borate [BH(DMPz)3] MoOCl2-C6H5Cl[BH(DMPz)3] 82JCR(S)6 ... 

Another possibility is that both nitrogen atoms react with a double alkylating agent. In this way fused pyrazole derivatives (pyrazolo[l,2-a]pyrazoles) like (237) can be obtained by reaction of 3,5-dimethylpyrazole with 1,3-dichloropropane or l-chloro-3-propanol (69BSF2064). More surprising is the reaction with a-chlorocarbonylphenylketene which yields the paraionic compound (238) (80JA3971) which can also be obtained from 3,5-dihydroxy-4-phenylpyrazole and /3-dicarbonyl compounds (82JOC295). 

With an activated C—C triple bond two successive additions can occur if the intermediate alkene is reactive enough. DMAD and 3,5-dimethylpyrazole give an initiaj fumarate (255) which reacts further at the other end to form regioselectively the succinates (256). On the other hand, methyl ethynyl ketone reacts twice at the same carbon atom with pyrazole to form 1,1-pyrazolylbutanone (258) (68ZC458). The probable intermediate, a pyrazolide vinylogue (257), can be prepared from methyl chlorovinyl ketone and pyrazole, in a reaction which is similar to acetylation (Section 4.04.2.1.3(x)). 

Phosphorus derivatives of different structures have been prepared including pyrazol-1-ylphosphines PPzs, PhPPz2 and Ph2PPz (Pz for pyrazolate anion (72CRV497,80MI40402)). By transamination with tris(dimethylamino)phosphine, pyrazoles and indazole are converted into (291) and (292), respectively (67CR(C)(265)1507). 3,5-Dimethylpyrazole reacts with amidodichlorophosphates to yield triamides (293) whereas 1-substituted pyrazolones yield amidophosphates (294) (71LA(750)39). 

Dimethylpyrazole (L) reacts with mercury(II) chloride to give complexes of the structure L2(HgCl2)3. In connection with metallotropy (Section 4.04.1.5.1) the behaviour of compounds (295) has been described. These phenylmercury derivatives were synthesized by the action of phenylmercury hydroxide on the appropriate pyrazole (71MI40400). 

In man, the metabolic pathways of mepirizole were distinct from those in experimental animals, since hydroxylation on each of the aromatic rings did not occur in man. Compound (752) was obtained by oxidation of the 3-methyl group to the carboxylic acid (a similar process occurs with 5-methylpyrazole-3-carboxylic acid, an active metabolite of 3,5-dimethylpyrazole). However, the carboxylic acid metabolite of mepirizole had no analgesic activity and did not decrease blood glucose. 

Acetophenone (6) 3 5 Dimethylpyrazole (580 mg, 6 mmol) was added to a suspension of Cr03 (600 mg 6 mrrx ) in CH2CI2 (20 mL) and the mixture was stirred at 20° under Ar for 15 min To this red solution ol 4 1 phenyiethanol 5 (263 mg 2 2 mmol) in CH2CI2 (2 mL) was added in one portion and the mixture was stirred for 30 min at 20° (GC imnitoring on Carbowax 20M) Evaporation, extraction with EI2O and evaporalion left a residue which was dissolved in pentane and filtered through silica Evaporation gave 280 mg of 6 (98%)... 

The first observation of the proton transfer in pyrazoles in the solid state was made for the intermolecular tautomerism in 3,5-dimethylpyrazole 10b (85JA5290). The degenerate rearrangement was recorded using the... 

Tautomeric rearrangements of transition-metal complexes with azole ligands are relatively scarce. The fluxional behavior of the rhodium complex 43 with a neutral 3,5-dimethylpyrazole was explained as the result of rapid processes of metallotropy and prototropy occurring simultaneously (Scheme 24) [74JOM(C)51],... 

Abbreviations acac, acetylacetonate Aik, alkyl AN, acetonitrile bpy, 2,2 -bipyridine Bu, butyl cod, 1,5- or 1,4-cyclooctadiene coe, cyclooctene cot, cyclooctatetraene Cp, cyclopentadienyl Cp, pentamethylcyclopenladienyl Cy, cyclohexyl dme, 1,2-dimethoxyethane dpe, bis(diphenyl-phosphino)ethane dppen, cis-l,2-bis(di[Atenylphosphino)ethylene dppm, bis(diphenylphosphino) methane dppp, l,3-bis(diphenylphosphino)propane eda,ethylenediamine Et,ethyl Hal,halide Hpz, pyrazole HPz, variously substituted pyrazoles Hpz, 3,5-dimethylpyrazole Me, methyl Mes, mesityl nbd, notboma-2,5-diene OBor, (lS)-endo-(-)-bomoxy Ph, phenyl phen, LlO-phenanthroline Pr, f opyl py, pyridine pz, pyrazolate Pz, variously substituted pyrazolates pz, 3,5-dimethylpyrazolate solv, solvent tfb, tetrafluorobenzo(5,6]bicyclo(2.2.2]octa-2,5,7-triene (tetrafluorobenzobanelene) THE, tetrahydrofuran tht, tetrahydrothicphene Tol, tolyl. 

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