Ketones tautomers

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

The one-electron chemistry of enols has been intensively studied by Schmit-tel [108]. He has shown that the thermodynamic stability order of the ketone tautomer and the enol tautomer in the solution phase is inverted upon one-electron oxidation [109, 110]. Therefore enols are much more easily oxidized than the corresponding ketone tautomer. Supposing that the enolization is faster than the electron transfer, it ought to be possible to oxidize the enol present in small amounts beside the ketone in the equilibrium mixture. The following cyclization reactions are as useful approach to the chemistry of enol radical cations and can be considered as the a-umpolung of ketones. 

In addition Levin et al. (70MI3) formulated a hydrogen-bridged analog of 30d and a ketone tautomer (7-oxo-6,7-dihydro-TP). Zwitterionic structures for 30a (60JA605), 30b (59JOC779), and the N-alkyl derivatives (68T2839) were also considered. 

Eberbach and coworkers have made an extensive study of the thermal chemistry and photochemistry of ethenyloxiranes (81CB1027 and refs, therein). Thermal isomerization can involve mainly either C—O (Scheme 8) or C—C (Scheme 9) cleavage. The reluctance of (11) to generate an ylide may be due to the fact that allowed, conrotatory opening would give a strained species (12) (cf. OEO-cycloheptene). The photoisomerization of ethenyloxiranes can involve either C—O (Scheme 10) or C—C (Scheme 11) cleavage. Photolysis of (13) led to the synthesis of the ketone tautomer (14) of a phenol (Scheme 12) (80TL463). 

III,D, 1). In spite of this, differences in the spectra of 5-anilino-3-hydroxy- and 3-alkoxy-5-anilino-l,2,4-thiadiazoles suggest that ketonic tautomers of the hydroxy compound contribute to the resultant absorption curve. Similar observations are made with 3-hydroxy-5-phenyl-l,2,4-thiadiazole.122 The spectra of 4-methylpyrimid-2-one and 2-methoxy-4-methylpyrimidine led to similar conclusions.170... 

With perfluoroquinoline, fluorine is replaced by hydrolysis in the 2- and 4-positions, likewise giving the ketonic tautomers pcrfluoroquinolin-2( 1 //)-one (8) and perfluoroquinolin-4(l H)-one (9).5 3... 

Aromatic enols, that is, phenols, are generally more stable than their ketone tautomers. The pH-rate profile for the enolization reaction of 2,4-cyclohexadienone to parent phenol is shown in Fig. V.44 The rate constant kK of the reverse reaction was determined at pH = 1 by measuring the rate of isotopic exchange and correcting for isotope effects to determine the enolization constant Kb = = 5.4 x 1012, pA E = -12.73. The dashed line in... 

In a retrosynthetic sense, formal hydrolysis of the carbon-nitrogen bond of 1.21 reveals enol 1.22 which would exist as the more stable ketone tautomer 1.23. Note that in the hydrolytic disconnection step the carbon becomes attached to a hydroxy group and the nitrogen to a hydrogen atom - there is no change in the oxidation levels of carbon or nitrogen. 

Anklam, E., Ghaffari-Tabrizi, R., Hombrecher, H., Lau, S., and Margaretha, P. (1984) Synthesis and photochemistry of 2,2-dimethyl-3(2H)-fhiophenone, a ketonic tautomer of 3-hydroxythiophene. Helvetica Chimica Acta, 67, 1402-1405. 

To complete the tautomerizatton, it is necessary only for a base, such as water, to remove the proton on the oxygen. The tautomerization is fast in both directions, but the equilibrium greatly favors the ketone tautomer. 

How can one use this thermochemical effect for a preparative route to enol radical cation intermediates in solution Since one usually has to start with the ketone tautomer, two possibilities are conceivable at first from Fig. 2 (1) direct oxidation of the ketone to the ketone radical cation followed by a 1,3-hydrogen migration to provide the enol radical cation, or (2) selective one-electron oxidation of the enol that is present in the equilibrium situation under fast enolization conditions. 

Enols are much more easily oxidized than the corresponding ketone tautomers, however, their tendency to ketonize rapidly has precluded extensive electrochemical and other one-electron oxidation studies so far. Hence, oxidation potentials were only determined of few relatively stable enols of fi-dicarbonyl compounds or a-cyano ketones, where the enol content may be as... 

For example, addition of 2 equivalents of a nonnucleophilic base, 2,6-di-tert-butylpyridine, to the reaction system almost totally suppressed the reaction (Table 9). This proposes that acid catalyzed enolization is important for the a-Umpolung. In support of mechanism 1 the yields of the a-methoxylated products increased with decreasing oxidation strength of the oxidant (Table 10), since endergonic oxidation of the ketone 70 is slowed down (Fig. 2). On the other hand, in the presence of stronger aminium salts the ketone tautomer is oxidized which however does not lead to deprotonation in the benzylic position... 

Compound (127 R = OH) exists in solution as a mixture with its red enamino-ketone tautomer and gives [127 R = CH=C(OAc)a] by further reaction... 

Studies of simple furan-3-ol derivatives are still sparse. The ketonic tautomers are better known in the sense that 2,2-disubstitution stabilizes them not only against isomerization but also against oxidation. These non-enolizable ketones are considered very briefly. 

Oxadiazoles," 1,3,4-oxadiazoles" and 1,2,5-oxadiazoles are well known, but the 1,2,3-oxadiazole system, which calculations indicate to be unstable relative to its ring-open diazo-ketone tautomer," is known only as a benzo-fused derivative (in solution) and in mesoionic substances, known as sydnones ," which have been well investigated. Furoxans ," which are formed by the dimerisation of nitrile oxides, have also been extensively studied. 1,2,3-Thiadiazoles, 1,2,4-thiadiazoles, 1,3,4-thiadiazoles" and... 

When pyruvate kinase transfers the phosphoryl group from phosphoenolpyruvate to ADP, the remaining enediol reminant, enolpyruvate, is much more unstable than its ketone tautomer, pyruvate. This enol-ketone tautomerization drives the overall reaction toward ATP formation by removing the enolpyruvate by converting it to pyruvate. 

After the protonation of the ketone, one of the methyl groups is deprotonated, resulting in the formation of a ketone tautomer with a tetraenol structure. 

Of tie potential tautomeric forms of 5-hydroxyisothiazole, the ketonic tautomers predominate in the solid state, as shown by spectral data the hydrojy-form makes but a small contribution in solution (see ref. 38, below ... 

Notice that enamines are the nitrogen counterpart of enols (p. 448). Now comes an important question Why doesn t the iminium ion formed from primary amines or ammonia (Fig. 16.49) also lose a proton from carbon to give an enamine Why is imine formation preferred when there is a choice (Fig. 16.55) The answer is extraordinarily simple Just as the ketone tautomer is more stable than the enol, the imine is more stable than the enamine and so is preferred when possible. It is only in cases where imine formation is not possible, as when secondary amines are used, that enamines are formed. We hope you have noticed that the imine- and enamine-forming reactions are reversible. The reactions work best under slightly acidic conditions with heat applied to drive off water. If water is added to an imine or enamine, the reverse reaction occurs to yield the carbonyl compound and an amine. 

Keto-enol-enolate rate and equilibrium constants have been reported for N-methylindoline-2-one (90), its 2-thione, and its 2-selone, i.e. a lactam, a thiolactam, and a selenolactam. As an example, the ketone tautomer of the thione has an acidity constant of 8.93, and that of its enoT is 4.05, giving a tautomerization constant, pACe. of 4.88. 

There are many aromatic compounds that are in equilibrium with their tautomers. Therefore, it is possible to target the tautomers as direct RCM products for the synthesis of aromatic compounds. Scheme 26.19 shows an RCM/tautomerization sequence used to synthesize naphthol 68 by van Otterlo et al. [25]. The direct product by RCM of diene 66, which contains a carbonyl group, was ketonic tautomer... 

Stannyl enol ethers are prepared typically from the corresponding metal enolates and tin electrophiles. A convenient protocol is the reaction of enol carboxylate with tin alkoxide (Scheme 3-190). In contrast to silyl enol ethers, stannyl enol ethers usually exist as mixtures of C-Sn (ketone) and O-Sn (enol ether) forms. For example, acetone and carboxylate esters exist mostly as a C-Sn (ketone) form. In general, the 0-Sn (enol ether) tautomers are more nucleophilic to react with electrophiles faster than the C-Sn (ketone) tautomers. 

The formulation of 2,l-benzisothiazolin-3-one as ketonic tautomers (see Vol. 3, p. 558) has been confirmed by the preparation of its N- and O-alkylated derivatives, by unambiguous routes, and examination of their u.v. spectra. The same conclusions have been reached about 5-chloro-2,l-benzisothiazolin-3-one. Other nucleophilic displacements of the 3-halogen in 3-chloro- and 3,5-dichloro-2,1-benzisothiazole have been reported the auxin analogue (72 R = CHgCOaH) was obtained in the course of this work. The results of a comparative study of the rates of A -methylation are included under isothiazoles (p. 344). 

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