Reaction with pyrazolones

Amino and sulfur analogues of pyrazolones also yield the aromatic quaternary salt (231 X = NH or S). If the pyrazole bears a substituent with a second pyridine-like nitrogen atom, an intramolecular bridge can be formed by reaction with a dihalogenoalkane. Thus pyrazol-I -ylpyridines react with 1,2-dibromoethane to form (233) (81JHC9). 

The reaction has been extended to indazole (67BSF2619) from which both isomers have been obtained, and to pyrazolones (68BSF5019). In the latter system N-, O- and C-aryl and even diaryl derivatives have been isolated from the reaction with l-fluoro-2,4-dinitrobenzene. 

Pyrazolones show a great variety of reactions with carbonyl compounds (B-76MI40402). For instance, antipyrine is 4-hydroxymethylated by formaldehyde and it also undergoes the Mannich reaction. Tautomerizable 2-pyrazolin-5-ones react with aldehydes to yield compound (324) and with acetone to form 4-isopropylidene derivatives or dimers (Scheme 8 Section 4.02.1.4.10). 

However, when 3,5-diphenyl-4//-pyrazol-4-one, a reagent that undergoes Diels- Alder reactions with inverse-electron demand, is used, addition of the 2,4-diene part of oxepin to one of the two C-N double bonds of the pyrazolone is observed to give 4.232... 

It is known that certain coumarins are transformed into 5-(2-hydroxy-phenyl)-3H-pyrazol-3-ones by reaction with hydrazines [10]. Upon appUca-tion of this method, the expected pyrazolones 25 were synthesized starting from 3-nitrocoumarins [11] as known in (Scheme 6). 

Many of the modifications of the pyrazolone antiinflammatory agents are intended to increase the limited hydrophilicity of the parent molecules. Reaction of aminopyrine (157) with formaldehyde and sodium hydrogen sulfite affords dipyrone (158). The first step can be rationalized as an Eschweiler-Clark type N-methylation reaction, with bisulfite acting as the reducing agent. The resulting mono N-methyl analogue of 157 then apparently forms the sulfite adduct of the carbinolamine of formaldehyde. 

Another sequence involving an anionic and a Pd-catalyzed step was described by the groups of Rossi and Arcadi [477]. These authors prepared substituted tetrahy-dro-2H-pyrrolo[3,2-c]pyrazolones 2-934 starting from hydrazones 2-932 and aryl-halides or alkenyl triflates 2-933 (Scheme 2.208). The first step is the formation of a pyrazolone. There follows cleavage of the urea moiety with piperidine and an inter-as well as an intramolecular Heck-type reaction with 2-933. 

The reaction of pyrazolones (207) with 3-oxo-esters gives mainly the pyrazolo[l,2-a]pyrazol-l,5-(lff,5//) diones (208). However, with 207 (R = Ph), only oxazines 209 are obtained. Thermal and photochemical isomerization of 204 gives 209 (84CPB930, 84JAP59128384). Phenace-tylpyrazole (210) is cyclized to 211 with thiophosgene (84JOC3672). 

Euro[3,4-/ ]pyridine diones undergo condensation reactions with a variety of active methylene compounds such as 3-thiophenacetonitrile, creatinine, and pyrazolone to afford 7-substituted furo[3,4-3]pyridinones in excellent yields (70-88%) <1999SC3773>. 

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). 

NaOH addition to water solution, multiple-step extraction on Extrelut QE columns with CHC13, H2S04 addition, evaporation. H2S04 addition, dia-zotization, and coupling reaction with R-salt or pyrazolone for aniline. 

The reaction of pyrazolone bearing a /3-ketoester moiety with aliphatic dibasic functional reagents in EtOH afforded binary ring heterocycles. Whereas when using an excess of a dibasic reagent, dipyrazolo[3,4-z 3, 4 -/][l,2]di-azepine derivatives were obtained <2001SC1335>. 

The product of the reaction of 3-methyl-l-phenyl-5-pyrazolone with chloride 21c in ethanol in the presence of sodium ethoxide was assigned structure 232 (83MI1). Neither spectral nor elemental analysis data were given to support such an ambiguous assignment, however. As the 5-pyrazolone derivative is an active methylene compound, its reaction with hydrazonoyl halides 21c is expected to give pyrazolo[3,4-c]pyrazole derivative 233, not 232. 

Reaction of chlorosulfonic acid with mono- [141] or disazo dyes [142] yields sulfonyl chlorides, which can then be transformed into cationically substituted sulfonamides by reaction with dialkylaminoalkylamines. The coupling product of diazotized 2-anisidine with 2-hydroxynaphthoic acid arylide upon such treatment dyes paper red, and the azo dye from tetrazotized dianisidine and l-phenyl-3-methyl-5 -pyrazolone gives yellowish orange shades. 

Numerous cationic azo dyes are prepared by the action of /V-hydroxymcthyl-chloroacetamide on azo dyes in sulfuric acid medium, followed by displacement of the reactive chloro substituent by pyridine or trialkylamine. Of special significance for dyeing paper are dyes that are prepared by coupling of diazotized 2-(4 -aminophenyl)-5-methylbenzothiazole to acetoacetaiylides, pyrazolones, naphthols [143], or barbituric acid derivatives [144], followed by reaction with N-hydroxymethylchloro-acetamide and pyridine. The azo dye obtained by oxidative dimerization of 2-(4 -aminophenyl)-5-methylbenzothiazole may also be subjected to this conversion [145], Dye 51 colors paper yellow. 

---