Tautomerism pyrazolone

The tautomerism shown by the pyrazolones is of considerable interest. Thus the above methyl"-phenyl pyrazolone when fused or in solution can exist in the tautomeric forms (C), (D), and (E). 

The main appHcation of nmr in the field of pyrazolines is to determine the stereochemistry of the substituents and the conformation of the ring. For pyrazolones, nmr is useful in estabUshing the stmcture of the various tautomeric forms. Table 2 summarizes the chemical shifts of a few representative derivatives. 

Pyrazolones. The 0x0 derivatives of pyrazolines, known as pyrazolones, are best classified as follows 5-pyrazolone, also called 2-pyrazolin-5-one [137-44-0] (36) 4-pyrazolone, also called 2-pyrazolin-4-one [27662-65-3] (37) and 3-pyrazolone, also called 3-pyrazolin-5-one [137-45-1] (38). Within each class of pyrazolones many tautomeric forms are possible for simplicity only one form is shown. 

Substitution at decreases the possible number of tautomers for 3-pyrazolones, two tautomeric forms are possible, (39) and (40), which in nonpolar solvents are both present in about the same ratio. 5-Pyrazolones exhibit similar behavior. 

The tautomeric character of the pyrazolones is also illustrated by the mixture of products isolated after certain reactions. Thus alkylation normally takes place at C, but on occasion it is accompanied by alkylation on O and N. Similar problems can arise during acylation and carbamoylation reactions, which also favor C. Pyrazolones react with aldehydes and ketones at to form a carbon—carbon double bond, eg (41). Coupling takes place when pyrazolones react with diazonium salts to produce azo compounds, eg (42). 

In mordant dyes, phenols, naphthols, and enolizable carbonyl compounds, such as pyrazolones, are generally the couplers. As a rule, 2 1 metal complexes are formed ia the afterchroming process. A typical example of a mordant dye is Eriochrome Black T (18b) which is made from the important dyestuff iatermediate nitro-l,2,4-acid, 4-amiQO-3-hydroxy-7-nitro-l-naphthalenesulfonic acid [6259-63-8]. Eriochrome Red B [3618-63-1] (49) (Cl Mordant Red 7 Cl 18760) (1, 2,4-acid — l-phenyl-3-methyl-5-pyrazolone) is another example. The equiUbrium of the two tautomeric forms depends on the nature of the solvent. 

Together with pyridones, the tautomerism of pyrazolones has been studied most intensely and serves as a model for other work on tautomerism (76AHC(Sl)l). 1-Substituted pyrazolin-5-ones (78) can exist in three tautomeric forms, classically known as CH (78a), (DH (78b) and NH (78c). In the vapour phase the CH tautomer predominates and in the solid state there is a strongly H-bonded mixture of OH and HN tautomers (Section 4.04.1.3.1). However, most studies of the tautomerism of pyrazolones correspond to the determination of equilibrium constants in solution (see Figure 20). 

Hydrogen bonding plays a major role in pyrazolone tautomerism, and the formation of a chelate structure can shift the equilibrium towards the chelated form. Structures (135) and (136) are two representative examples of such stabilized tautomers. Structure (137) is a hypothetical example of stabilization of the NH tautomer. 

A theoretical, comparative study of the tautomerism of 56 five-membered heterocyclic rings announced in (76AHC(Sl)l) has appeared (81MI40402). The stabilities of the three forms for 5-pyrazolones, 5-pyrazolethiones and 5-aminopyrazoles have been calculated by a simple Hiickel o) iterative method. The relative energies and the substituent and solvent effects are in agreement with the experimental results. 

A parallel exists between the results of protonation and alkylation of pyrazolones since there is an alkyl derivative for each tautomer. The main difference is that the percentage of the different tautomers is thermodynamically controlled whereas that of alkyl derivatives is kinetically controlled. One has to remember that the alkyl derivatives thus obtained are the fixed compounds used in tautomeric studies. 

The acetyl transfer reactions of acetylated pyrazolones (acylotropy) have been carefully studied by Arakawa and Miyasaka (74CPB207,74CPB214) (Section 4.04.2.1.3(x)). Methylation of 3-methyl-l-phenyl-4-phenylazo-5-pyrazolone (402) yields, depending on the experimental conditions, the N- and the O-methylated derivatives (483) and (484) (66BSF2990). These derivatives have been used as model compounds in a study of the tautomerism of (402) (structure 139 Section 4.04.1.5.2). 

X-Ray crystal structure determinations of l-(aminocarbonyl)-3-methyl-4-methoxy-l//-pyrazol-5(2H)-one 107 (R = H) and l-(phenylaminocar-bonyl)-3-methyl-4-methoxy-l//-pyrazol-5(2H)-one 107 (R = Ph) demonstrated that both molecules exist in the crystal exclusively as NH-CO tautomers (97T5617). The tautomeric form similar to 104b is realized in the crystal of 4,4-dichloro-substituted pyrazolone 108 (93BSB735). 

Another type of tautomerization was observed in the complexation reaction of 5-oxo tautomers of pyrazolone with metal chlorides 362 (89ZNK 2966). 

Where keto-enol tautomerism is possible, not surprisingly the keto form is preferred. Thus of three possible tautomeric structures 100,1,8 IR and UV data favor 100c.120 Likewise, rearrangement of the 4-hydroxy-4//-pyrazoles 101 gives the pyrazolones 103 via the enols 102 (Scheme 37).133... 

The tautomerism of 4//-pyrazolones has been discussed.62 Of the three forms 54-56 that might exist in equilibrium, there is no spectroscopic evidence for 55 or 56.32 Likewise 24 does not appear to be in equilibrium with its dihydroxy tautomer.35... 

The situation in the pyrazolone-azo dye series is more complex. In contrast to former assumptions the dyes are inaccurately described as azo compounds and in fact exist exclusively in a tautomeric phenylhydrazone form. The simple pyrazolone dye (116 R=H) absorbs at 398 nm in ethanol (67BCJ1239). In this instance the pyrazolone heterocyclic ring... 

Fig. 4.13. illustrates how to apply carbon-13 NMR for analysis of tautomerism in heterocyclic chemistry 3-Methyl-5-oxo-l-phenyl-4,5-dihydropyrazole (the Knorr-pyrazolone ) is shown to exist as the CH tautomer B with a CH2 carbon at 43.1 ppm in chloroform solution (Fig. 4.13(a)), while the OH tautomer A predominates (90%) in hexadeuteriodimethyl sulfoxide (Fig. 4.13(b) [73 i]. 

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