Pyrazole sulfonation

As with nitration, sulfonation proceeds only with difficulty due to cation formation. Knorr sulfonated 3-methylpyrazole in the 4-position by heating it at 100° for 6 hours in 20% oleum.208 Pyrazole sulfonic... 

Pyrazoles 171 were sulfonated with concentrated sulfuric acid in the presence of acetic anhydride to give pyrazole-sulfonic acids 172 (Equation 26) <1997CHE532>. 

Chou used an alternative route to a number of pyrazole sulfones starting from the dihydrothiophene 31 (Scheme 26) <93JOC493 93H(35)2839>. The same dihydrothiophene was also used as the starting point for isoxazole <92TL8121> and pyrrole <92CC549> fused sulfones as precursors for the respective o-quinodimethanes (Scheme 26). 

Amination at an azole ring nitrogen is known for Af-unsubstituted azoles. Thus 4,5-diphenyl-1,2,3-triazole with hydroxylamine-O-sulfonic acid gives approximately equal amounts of the 1- (104) and 2-amino derivatives (105) (74AHC(16)33). Pyrazole affords (106) and indazole gives comparable amounts of the 1- and 2-amino derivatives. 

In azole chemistry the total effect of the several heteroatoms in one ring approximates the superposition of their separate effects. It is found that pyrazole, imidazole and isoxazole undergo nitration and sulfonation about as readily as nitrobenzene thiazole and isothiazole react less readily ica. equal to m-dinitrobenzene), and oxadiazoles, thiadiazoles, triazoles, etc. with great difficulty. In each case, halogenation is easier than the corresponding nitration or sulfonation. Strong electron-donor substituents help the reaction. 

Azolesulfonic acids frequently exist as zwitterions. The usual derivatives are formed, e.g. pyrazole-3-, -4- and -5-sulfonic acids all give sulfonyl chlorides with PCI5. The sulfonic acid group can be replaced by nucleophiles under more or less vigorous conditions, e.g. by hydroxyl in imidazole-4-sulfonic acids at 170 °C, and by hydroxyl or amino in thiazole-2-sulfonic acids. 

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. 

Pyrazolesulfonic acids, like (493), have high melting points (Table 24) and probably exist as the zwitterions (497). They are very stable to hydrolysis and only afford pyrazolones at high temperatures. The replacement of the SO3H group by bromine has also been reported (B-76MI40402). Pyrazole-3-, -4- and -5-sulfonic acids react with phosphorus pentachloride to form sulfonyl chlorides. 

Anthra[l,9]pyrazol-6(2//)-one (735) dyes have also been described in the literature (B-70MI40403). TTiesc compounds result by acid ring closure of 1-anthraquinonyl hydrazine or its V-sulfonic acid. 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

The following compounds have been obtained from thiete 1,1-dioxide Substituted cycloheptatrienes, benzyl o-toluenethiosulfinate, pyrazoles, - naphthothiete 1,1-dioxides, and 3-subst1tuted thietane 1,1-dioxides.It is a dienophile in Diels-Alder reactions and undergoes cycloadditions with enamines, dienamines, and ynamines. Thiete 1,1-dioxide is a source of the novel intermediate, vinylsulfene (CH2=CHCH=SQ2). which undergoes cyclo-additions to strained olefinic double bonds, reacts with phenol to give allyl sulfonate derivatives or cyclizes unimolecularly to give an unsaturated sultene. - Platinum and iron complexes of thiete 1,1-dioxide have been reported. 

Bis(alkynyl)-l//-pyrazoles are also obtained by the same procedure. The reaction of (Z)-enediyne sulfones with diazomethane gives bis(alkynyl)-3//-... 

Similar peculiarities had been noted previously on nitration of phenylpyridines - and pyrazoles as well as on sulfonating phenylpyrazoles. ... 

Recently, the pyrazole group containing bisphenols have been synthesized from activated aromatic dihalides and 3,5-bis (4-hydroxy phenyl)-4-phenyl pyrazole or 3,5-bis(4-hydroxy phenyl)-1,4-diphenyl pyrazole. A novel synthesis of imido aryl containing bisphenols has been reported [32]. N-substituted l,4-bis(4-hydroxy phenyl)-2,3-naphthalimides were prepared from phenolphthalein and copolymerized with aromatic sulfone or ketone difluorides to obtain the poly(imidoaryl ether) sulfones/ ketones. 

Metalation of 2 with lithium diisopropylamide (LDA) generates diazo(trimethyl-silyl)methyl hthium (3), which reacts with a,p-unsaturated nitrile 36 and phenyl-sulfones (37) to form 3(or 5)-trimethylsilyl-l//-substituted pyrazole 4 that can be desilylated to furnish pyrazoles 5 (Scheme 8.3). 

In addition to those methods described in CHEC(1984) and CHEC-II(1996) (primarily alkylation and acylation reactions), Vicentini <1996T7179> has shown that 5-methylimidazo[4,5-f]pyrazole 28 can undergo electrophilic attack on nitrogen by hydroxylamine 0-sulfonic acid to yield the 4-amino species 29 (Equation 1). 

---