Pyrazole-4-sulfonic acid

The corresponding 4-halopyrazoles are produced by the action of chlorine or bromine in acetic acid. Nitrating acid yields 4-nitropyrazoles and, dependent on the substituents in the pyrazole ring, reaction takes place either with pyrazole itself or the pyrazolium ion. Sulfonation involves the pyrazolium ion. For this reason, heating in oleum is necessary, which leads to pyrazole-4-sulfonic acid. Pyrazoles with substituents in the 1-position yield pyrazole-4-carbaldehyde in the Vilsmeier-Haack formylation and are amenable to Friedel-Crafts acylation. 4- and 5-aminopyrazoles can be diazotized. 

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

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. 

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. 

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. 

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). 

Pyrazoline-3- or -5-carboxylic acids, their derivatives, and the derivatives of the corresponding sulfonic acids are oxidized by bromine to the corresponding pyrazoles in yields of 50-75%. 4,15S-402-484-506... 

The molecule contains a sulfonamide and a benzene ring as well as the part that interests us most—a bicydic aromatic heterocyclic system of a pyrazole fused to a pyrimidine. We shall discuss in detail how Pfizer made this part of the molecule and just sketch in the rest. The sulfonamide can be made from the sulfonic acid that can be added to the benzene ring by electrophilic aromatic sulfonation (Chapter 22). 

Strong oxidation (e.g., by RMnO. ) forms a sulfonic acid or betaine as, for example, in the pyrazole (750 751), imidazole, thiazole, and tetrazole series. 

C. Coupling of Pyrazol-3-ones with 4-Diazo-3-oxo-3, 4-Dihydronaphthalene-1-Sulfonic Acid... 

Coupling of pyrazole-3-ones 223a-d with 4-diazo-3-oxo-3,4-dihydronaphthalene-1-sulfonic acid 224 in aqueous ethanol with sodium hydrogen carbonate afforded the requisite 4-dihydronaphthalenehydrazonopyrazol-3-ones 225a-d in excellent yield and purity in the majority of cases (01JMC3730) (Scheme 71). 

Flavazin L has already been described as a textile dye derived from pyrazolone. Tartrazine 5 is one of the few synthetic dyes which are approved for colouring foodstuffs and cosmetics. The yellow compound, which is the trisodium salt, is produced by coupling 2,4-dihydro-3//-pyrazol-3-ones with diazo-tized sulfanilic acid. The required pyrazole is accessible from diethyl 2-oxobutanedioate and 4-hydrazinobenzene-1-sulfonic acid. 

Sodium (antipyrinylmethylamino) methanesulfonate monohydrate Methane-sulfonic acid, [(2, 3-dihydro-l, 5-dimethyl-3-oxo-2-phenyl-lH-pyrazol-4-yl) methylamino]-, sodium salt, monohydrate Analginum Metamizol Amino-pyrine-sulphonate sodium ... 

The first report of the use of cellulose beads as support for microwave-assisted SPOS was published in 2003 and described the generation of a library of pyrazoles and isoxazoles [49]. The synthesis was performed using commercially available amino cellulose (Perloza VT-100) containing aminoaryl ethyl sulfone groups in flexible chains (Scheme 16.27). Initially, the solid support was treated with excess formyl imidazole and the corresponding yS-keto compounds to generate cellulose-bound enaminones in a one-pot Bredereck-type condensation. The reaction was catalyzed by (+)-camphor-10-sulfonic acid (CSA) and performed under microwave-irradiation conditions in an open vessel to enable the methanol formed to be removed from the reaction equilibrium [49]. 

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