Pyrazolium salts

Base-catalyzed hydrogen exchange occurs at the 3- and 5-positions of 1,2-dimethyl-pyrazolium salts. 2-Unsubstituted 1,3-dithiolylium salts are easily deprotonated by nucleophilic attack of hydrogen. The intermediate carbene easily undergoes dimerization. Hydrogen exchange can also occur (Scheme 23) (80AHC(27)15l). 

Dithiolylium salts (483) may be converted into pyrazoles, pyrazolium salts and isothiazoles depending on the type and degree of substitution of the nitrogen source. 

The mesoionic compounds are derived from pyrazolium salts (22) when R is replaced by a negatively charged heteroatom, like the anhydro-4-hydroxypyrazolium hydroxide (28). According to Ollis and Ramsden (76AHC(l9)l) they belong to the mesoionic class B type. 

The behaviour under electron impact of IV- and C-trimethylsilylpyrazoles (mono-, di-and tri-substituted) has been studied by Birkofer et al. (740MS 8)347). Loss of a methyl radical followed by loss of HCN is the most common fragmentation feature of these compounds. When more than one trimethylsilyl group is present, a neutral fragment CaHgSi is expelled. Mass spectrometry of pyrazolium salts has been studied by Larsen etal. (8i OMS377, 830MS52). 

The general discussion (Section 4.02.1.4.1) on reactivity and orientation in azoles should be consulted as some of the conclusions reported therein are germane to this discussion. Pyrazole is less reactive towards electrophiles than pyrrole. As a neutral molecule it reacts as readily as benzene and, as an anion, as readily as phenol (diazo coupling, nitrosation, etc.). Pyrazole cations, formed in strong acidic media, show a pronounced deactivation (nitration, sulfonation, Friedel-Crafts reactions, etc.). For the same reasons quaternary pyrazolium salts normally do not react with electrophiles. 

Very little is known about nucleophilic attack on an unsubstituted carbon atom of pyrazoles and their aromatic derivatives (pyrazolones, pyrazolium ions). The SwAr reaction of halogenopyrazoles will be discussed in Section 4.04.2.3.7. Sulfur nucleophiles do not attack the ring carbon atoms of pyrazolium salts but instead the substituent carbon linked to nitrogen with concomitant dequaternization (Section 4.04.2.3.lO(ii)). The ring opening of pyrazolium salts by hydroxide ion occurs only if carbon C-3 is unsubstituted the exact mechanism is unknown and perhaps involves an initial attack of OH on C-3. 

Only two topics are of importance for this section the reduction of pyrazolium salts and 3-pyrazolin-5-ones by complex hydrides, and the nucleophilic photosubstitution of pyrazoles and indazoles. 

A mechanism has been proposed to rationalize the results shown in Figure 23. The relative proportion of the A -pyrazolines obtained by the reduction of pyrazolium salts depends on steric and electronic effects. When all the substituents are alkyl groups, the hydride ion attacks the less hindered carbon atom for example when = Bu only C-5 is attacked. The smaller deuterohydride ion is less sensitive to steric effects and consequently the reaction is less selective (73BSF288). Phenyl substituents, both on the nitrogen atom and on the carbon atoms, direct the hydride attack selectively to one carbon atom and the isolated A -pyrazoline has the C—C double bond conjugated with the phenyl (328 R or R = Ph). Open-chain compounds are always formed during the reduction of pyrazolium salts, becoming predominant in the reduction of amino substituted pyrazoliums. 

Figure 23 Reduction by complex hydrides of pyrazolones, thiopyrazolones, iminopyrazolines and pyrazolium salts...

Neither pyrazoles nor pyrazolium salts react by this mechanism which has been described for imidazoles and imidazolium salts (Section 4.01.1.7.4). As exchange rates show (Section 4.04.2.1.7(iii)), it is considerably more difficult to generate an ylide from a pyrazolium salt than from an imidazolium salt (at C-2). 

A -Pyrazolines such as (410) are oxidized by iodine, mercury(II) acetate and trityl chloride to pyrazolium salts (411), and compound (410) even reduces silver nitrate to Ag° (69JOU1480). Electrochemical oxidation of l,3,5-triaryl-2-pyrazolines has been studied in detail (74BSF768, 79CHE115). They Undergo oxidative dimerization and subsequent transformation into the pyrazole derivative (412). 

Analogous to the oxidation of hydrazones to azo compounds, A-unsubstituted pyrazolidines are oxidized to A -pyrazolines. For example, the blcyclic pyrazolidine (415) when treated with silver oxide yields the pyrazoline (416) (65JA3023). Pyrazolidine (417) is transformed into the perchlorate of the pyrazolium salt (411) by reaction with mercury(II) acetate in ethanol followed by addition of sodium perchlorate (69JOU1480). 

The acidic character of the hydrogen atoms of C-methyl groups linked to the pyrazolium ring (Figure 22 Section 4.04.2.1.1(11)) facilitates a number of reactions difficult to carry out with neutral pyrazoles. Since efficient methods of dealkylation have been described (Section 4.04.2.3.lO(ii)), the synthesis via the pyrazolium salt is a useful alternative. The same behaviour is observed for indazolium salts, for example, nucleophilic addition to aromatic aldehydes (78JOC1233). 

Derivatives like (491 R = Me) can be de-5-methylated by Raney nickel in ethanol or concentrated hydrochloric acid. Acid hydrolysis of (491 R = acyl) also affords 5-mercap-topyrazoles, whereas alkaline hydrolysis of the pyrazolium salt (495) furnishes methanethiol and antipyrine. 

Owing to their particular interest two individual reactions will now be discussed separately. The reaction of methoxycarbonylhydrazine and 3-bromo-2,4-pentanedione affords, in addition to the expected pyrazole (608), a pyrazolium salt (609), the structure of which was established by X-ray crystallography (74TL1987). Aryldiazonium salts have been used instead of arylhydrazines in the synthesis of pyrazolines (610) and pyrazoles (611) (82JOC81). These compounds are formed by free radical decomposition of diazonium salts by titanium(n) chloride in the presence of a,/3-ethylenic ketones. 

Pyrazolino[2,3-c][l,2,3]triazoles, 5, 702 Pyrazolium hydroxide, l,2-dimethyl-3,5-diphenylanhydro-4-hydroxy-IR spectra, 5, 201 Pyrazolium salts dequatemization, 5, 269 H NMR, 5, 185 hydrogen exchange at ring carbon, 5, 245 mesoionic compounds, 5, 171 nitrodebromination, 5, 237 reactivity, 5, 217 reduction, 5, 68, 243 synthesis, 5, 156 UV spectra, 5, 199 Pyrazolium salts, amino-reactions, 5, 262 Pyrazolium salts, bromo-nucleophilic displacements, 5, 266 Pyrazolium salts, 1,2-dimethyl-deuteration, 5, 175, 245 hydrogen exchange, 5, 71 acid-catalyzed, 5, 239 reactions... 

Another type of diazafulvalenes was obtained by the condensation of sodium cyclopentadienide with l,2-dimethyl-3,5-dimethoxy- and -3,5-bis(methylsulfanyl)pyrazolium salts (94AP385). Under mild conditions displacement of MeZ groups in each case led to the diazafulvalenes 58. A... 

Table 15 Furo[2,3-c]pyrazolium and thieno[2,3-c]pyrazolium salts...

In pyrazolium salts a ring chlorine can be displaced by the more nucleophilic bromide, and nucleophilic substitutions of diazonium groups by halogen are also relatively common (especially for fluorination) with yields frequently 80% or higher [61CB1036 66CB3350 90JAP(K)02/304064],... 

In pyrazolium salts chlorine can be displaced quite readily by iodide (77BSF171), and Sandmeyer reactions have found application in the preparation of iodopyrazoles from their diazonium salts [90AHC(48)65 90JAP(K)02/304064]. 

Dithiolylium salts may be converted into pyrazoles, pyrazolium salts and isothiazoles (see Section 3.4.1.6.2.ii). For example, 3-phenyl-1,2-thiolylium salt (74) with hydrazine, methylhydrazine or phenylhydrazine yielded the corresponding pyrazoles (75). 3,4-Dimethyl-1,2-dithiolylium perchlorate (76) with ammonia gave 4,5-dimethylisothiazole (77). 

Two structures, cyclic and chain, have been found for the pyrazolio-radical 118 that are able to explain the electrochemistry of pyrazolium salts... 

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