Keto-phenol tautomers

Several other types of tautomerization are shown in Figure 3.7. In each case, the equilibrium lies well to the right. For keto-phenol tautomers, the favored phenol form is aromatic whereas the keto form is not. Enamines that have at least one hydrogen on the nitrogen are generally not stable and revert to the imine form. Aliphatic nitroso compoimds with a hydrogen attached to the adjacent carbon are also usually not stable and exist primarily as oximes. 

The compounds 2- (16) and 4-pyridone (38) undergo chlorination with phosphoms oxychloride however, 3-pyridinol (39) is not chlotinated similarly. The product from (38) is 4-chloropyridine [626-61-9]. The 2- (16) and 4-oxo (38) isomers behave like the keto form of the keto—enol tautomers, whereas the 3-oxo (39) isomer is largely phenolic-like, and fails to be chlotinated (38). 

A 13C-NMR spectroscopic study in solution of the tautomers of several anils derived from salicylaldehyde and from 2-hydroxynaphthalene-l-carbaldehyde having the same amino part (141-145, Scheme 17) has been reported.82 Variable-temperature NMR spectroscopy and comparison with appropriate models show that while salicylideneanilines exist as phenolic tautomers, naphthylidene-anilines exist as equilibrium mixtures containing appreciable amounts ofboth enol and keto tautomers, the latter being slightly predominant (Table 9). In fact, there is a negligible shift in the equilibrium on changing the electronic effect of the R substituent. 

The tautomerism of hydroxyarenes occupies a particular position among keto-enol tautomer transformations of various organic compounds because of the aforementioned loss of aromaticity. In contrast to carbonyl compounds (e.g. the keto form 1 is more energetically favored than the enol form 2 by 42 kJmoU , equation 1), the phenols 3 are much more stable than their keto tautomers (4 or 5) because the energy gained by... 

It should be noted that the keto-enamine tautomers of Schiff bases are observed always when the latter are derived from 2-hydroxynaphthaldehyde and aniline. However, in Schiff bases derived from salicylaldehyde and aniline, the new band at >400 nm in UV-Vis spectra was not observed in both polar and non-polar solvents, but it appeared in acidic media. In this workl which contains a quite good survey of the investigations of tautomerism in Schiff bases, the effects of the solvent polarity and acidic media on the phenol-imine keto-amine tautomeric equilibrium in systems 55 and 56 were reported. It was shown by H NMR and UV-Vis spectra that compound 55 is in tautomeric equilibrium of structures 55a and 55b in both polar and non-polar solvents (equation 17), whereas the tautomer 56b was not observed for compound 56 (equation 18) . ... 

The coordination of transition metals is known to influence the keto-enol tautomerism in the condensed phase" . The effect of coordination of bare Fe+ ions on the keto-enol equilibrium of phenol was investigated by means of generation of various cyclic [Fe,Cg, He, 0]+-isomers. These isomers were characterized by collisional activation (CA) and Fourier transform ion cyclotron resonance (FTICR) mass spectrometry" . It was shown that the energy difference between the phenol-iron complex 65 and the keto isomer 66 is not perturbed by the presence of the iron cation in comparison with the uncom-plexed isomers 3 and 4 (equation 25). Thus, the energy difference for both the neutral and the Fe+-coordinated systems amounts to ca 30 kJ moC in favor of the phenolic tautomer. 

The reaction that initially implicates a keto-enol tautom-erism eqniUbrium between B and C progresses with an intramolecular cycloaddition involving the CN group activated by the phenolic OH, followed by a tautomerization. The formation of the desired spiro derivatives 117 releases the catalyst 116, which begins another catalytic cycle. 

The nuclear magnetic resonance spectra of SchifF bases formed from primary amines and ortAo-hydroxy aldehydes and ketones show that the Schiff bases derived from l-hydroxy-2-acetonaphthone and from 2-hydroxy-1-naphthaldehyde exist as keto amines (7a) although their formation involves loss of most of the resonance energy of one of the aromatic rings When R is a phenyl group, the phenol-imine tautomer (7b) predominates Schiff bases derived from ortho-hydroxy aldehydes and ketones have the phenol-imine structure (8) . Evidently, in such compounds the keto-amine tautomer... 

For most simple phenols this equilibrium lies well to the side of the phenol, since only on that side is there aromaticity. For phenol itself, there is no evidence for the existence of the keto form. However, the keto form becomes important and may predominate (1) where certain groups, such as a second OH group or an N=0 group, are present (2) in systems of fused aromatic rings and (3) in heterocyclic systems. In many heterocyclic compounds in the liquid phase or in solution, the keto form is more stable, although in the vapor phase the positions of many of these equilibria are reversed. For example, in the equilibrium between 4-pyridone (118) and 4-hydroxypyridine (119), 118 is the only form detectable in ethanolic solution, while 119 predominates in the vapor phase. " In other heterocycles, the hydroxy-form predominates. 2-Hydroxypyridone (120) and pyridone-2-thiol (122) are in equilibrium with their tautomers, 121 and 123, respectively. In both cases, the most stable form is the hydroxy tautomer, 120 and 122. ... 

Whilst azo compounds prepared from diazonium salts and phenolic or keto-enol coupling components are often depicted in the hydroxyazo form (4.11), an alternative tautomeric structure can be drawn for such compounds (Scheme 4.19). This ketohydrazone tautomer (4.21) can, in cases where the azo and hydroxy groups are located on adjacent carbon atoms, exhibit hydrogen bonding between the two groups as shown. Similar pairs of structures, but without hydrogen bonding, can be drawn for p-hydroxyazo compounds. 

Table 8.6 shows that the equilibrium mixture consists of almost entirely keto form in the case of simple aliphatic and aromatic ketones, whereas significant amounts of enol tautomer are present in /J-diketones and /J-ketoesters. In these latter cases, the enol contains a conjugated tt electron system and an intramolecular hydrogen bond (30). Phenol exists entirely in the enol form, as the alter-... 

Ketenes have been detected as secondary photoproducts from the keto tautomers of 86 and 45. Formation of the ketene, observed from 86, implies that the keto tautomer of phenol is present, although below the limits of detection, during photolysis of 86 at 77 K.135... 

All unusual non-radical phenolic coupling has been observed in 4-substituted-2,6-diiodophenols.43 It is likely that the reaction which results in the liberation of iodine involves. S n2 attack by an ambident phenolate anion (5) on the a-iodo keto tautomer (6). 

It is also possible to examine the effect of oxygen substituents on the stability of arenonium ions. Wirz has studied keto-enol equilibria for phenol,151 naphthol (Wirz J, Personal communication), and anthrol.152,153 The tautomeric constants may be combined with p/y,s for protonation of the keto tautomer and ionization of the phenol to provide pifas f°r protonation of the aromatic ring of phenol and the phenoxide ion. As illustrated in Scheme 18 the unstable keto tautomer of phenol 22 was produced by photolysis of the bicyclooctene dione 21. Except in the case of the anthrone a pA a for protonation of the keto tautomer has not been measured directly. However, values can be estimated from the pfor protonation of the 4,4-dimethylated analog136 with a correction for the substituent effect of the methyl groups. 

The pifas for C-protonation of the phenols and phenoxide ions are compared with values for the unsubstituted aromatic molecules in Table 3. The focus on pKn rather than pAR is because the equilibrium constants for hydration of the keto tautomers of the phenols have not been measured or estimated. The values of Ap and ApKf show the magnitude of the oxygen substituent effects relative to the parent aromatic molecules. Again the substituent effects are large, and much larger for O (more then 20 log units) than OH ( 10 log units). At first, it is surprising that the effects are so similar for the benzene, naphthalene, and anthracene. Once more this arises because the pWa reflects the stability of... 

The enol tautomers of many ketones and aldehydes, carboxylic acids, esters and amides, ketenes, as well as the keto tautomers of phenols have since all been generated by flash photolysis to determine the pH rate profiles for keto-enol interconversion. Equilibrium constants of enolization, KB, were determined accurately as the ratio of the rate constants of enolization, kE, and of ketonization, kK, Equation (1). 

Arsaphenol shows strong phenolic properties 25>. It is more acidic than phenol. Unlike 4-hydroxypyridine, no significant amount of the keto tautomer 95 has been detected. 

The keto tautomer of phenol does not retain any of the resonance energy associated with the aromatic ring, while the keto tautomer of 2-hydroxypyridine does (compare with amide resonance). 

Pyrimidones exist as the amide tautomer 60 rather than the enol tautomer 59 unlike the case with phenols 61. The enol tautomer of a phenol 61 is aromatic but the keto tautomer 62 is not. 

Some metals show such a pronounced tendency to adopt rj4-butadi-ene coordination that this may override the driving force to aromaticity. Selected complexes of d8 M(CO)3 (M = Fe, Ru) fragments illustrating this point are included in Figure 6.29. Phenol is far more stable than its keto tautomer (cyclohexadienone), which may be stabilized, however, by... 

The naphthylamines may be prepared by reduction of the corresponding nitro compound, but they are readily accessible from naphthois by the Bucherer reaction The naphthol is heated, preferably under pressure in an autoclave, with ammonia and aqueous sodium hydrogen sulfite solution, when an addition-elimination sequence occurs. The detailed mechanism is not completely elucidated, but the Bucherer reaction is restricted to those phenols that show a tendency to tautomerize to the keto form, such as the naphthois and 1,3-dihydroxybenzene (resorcinol). Using 1-naphthol for illustration, the first step is addition of the hydrosulfite across the 3,4-double bond of either the enol or keto tautomer (Scheme 12.9). Nucleophilic attack by ammonia at the carbonyl group... 

More than 100 years ago Thiele and Lapworth put forward the hypothesis that the exclusive substitution of phenol at the ortho- and para-positions might be attributed to rapid equihbration of phenol 3 with the transient keto forms 4 and 5. Since that time, the keto-enol equilibrium ratio in phenol itself has been estimated repeatedly and by application of various research methods. Thus, ab initio 6-31G basis set calculations were recently carried out on the structures of phenol 3, and its keto tautomers 2,4-cyclohexadienone 4 and 2,5-cyclohexadienone 5 . Energy calculations were carried out by using the all-electron ab initio Hartree-Fock formalism (RHF) as well as 2nd-order Moller-Plesset formalism (MP2) on the RHF-optimized geometries. It was shown that phenol 3 is significantly more stable than dienones 4 and 5 by 47.4 and 42.5 kJ mor (RHF) as well as 72.5 and 70.6 kJ moH (MP2), respectively. An equilibrium constant 3 4 was estimated as 1.98 x 10, i.e. in excellent agreement with experimental results as shown below. 

The two keto tautomers of phenol 3, i.e. 4 and 5, were generated by flash photolysis of polycyclic precursors 6-8 in aqueous solution, and the pH-rate profiles of their 4 3 and 5 3 enolization reactions were measured. The rates of the reverse reactions, 3 4 and 3 5, were determined from the rates of acid-catalyzed hydrogen exchange at the ortho- and para-positions of phenol 3 (equation 3). 

The keto tautomers of monohydric phenols are frequently invoked as reactive intermediates in many reactions, such as the Reimer-Tiemann and Kolbe-Schmitt reactions , electrophilic substitution (e.g. bromination i) s well as the photo-Fries rearrangement (see Section IV.D and also Refs. 16-18 cited in Reference 7). In certain cases the keto... 

Such a phenol keto-tautomer equivalent strategy was used for conjugate reduction of cyclic enones (equation 5). The quinone monoketals 9 and para-quinol ethers 10 were used as precursors to keto-tautomer equivalents of substituted phenols, namely enones 11, which were prepared by action of bis(2,6-di-fert-butyM-methylphenoxy)methylaluminium (MAD), followed by addition of lithium tri-iec-butyl borohydride (L-Selectride). The enones 11 obtained are reasonably stable at a freezer temperature without aromatization. ... 

The tautomeric properties of hydroxynaphthalenes show in the most unambiguous manner that the naphthalene system is less aromatic than that of benzene. The benzoannelation appreciably destabilizes the aromatic tautomers not only among phenols but also in the arene series . Therefore, even the monohydroxy naphthalenes display in their chemical reactions properties typical for the tautomeric keto form. 

It was shown recently that K-region arene oxides can rearrange to phenols in two steps (i) rapid rearrangement of the arene oxide 28 forming the positionally isomeric keto tautomers 29 of the K-region phenols 30, followed by slow enolization to 30 (equation 11). 

An interesting situation arises when a tendency of ketodiene tautomer to transform into phenol results in a disturbance of the conjugation system in the whole structure in which this tautomer is a fragment. Thus, in the series of porphyrinoids 74 containing a semiquinone moiety, the macrocycle achieves the aromatization by undergoing a keto-enol tautomerization, whereby the phenolic subunit in structure 73 is transformed in such a way that the inner three carbon atom moiety becomes part of the 18 jt-electron... 

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