Tautomerism base-catalysed

Alkylation of potentially tautomeric heteroaromatic systems under basic phase-transfer catalytic conditions normally occurs on the softer heteroatom [cf 57]. Thus, although 2- and 4-pyridones are alkylated on the annular nitrogen atom and the exocyclic oxygen atom, -alkylation of the 2-pyridones predominates to the extent of ca. 5 1 (or greater under soliddiquid reaction conditions [58]), whereas the relative predominance of A -alkylation of the 4-isomer is only ca. 3 1 [59] (Table 5.37 and 5.38). These ratios are comparable with those obtained for the base-catalysed alkylation of the pyridones by traditional methods and, not unexpectedly, S-alkyla-tion of the corresponding pyridthiones occurs to the total exclusion of A-alkylation [60]. Catalysed soliddiquid acylation has also been reported [58]. 

The intermediacy of enols or enolate anions may be demonstrated by hydrogen exchange reactions (see Section 4.11.2). Both acid-catalysed and base-catalysed tautomerism mechanisms involve removal... 

Base-catalysed hydrolysis. The hydroxide ion attacks the nitrile carhon, followed hy protonation on the unstable nitrogen anion to generate an imidic acid. The imidic acid tautomerizes to the more stable amide via deprotonation on oxygen and protonation on nitrogen. The base-catalysed amide is converted to carboxylic acid in several steps as discussed earlier for the hydrolysis of amides. 

X,Y=0,S,Se,Te], has been undertaken.628 The stabilities of different tautomeric forms of 4-hydroxycoumarins have been evaluated629 by MNDO calculations, and the four lowest-energy oxo-hydroxy tautomers of 5-fluorouracil have been studied630 using density functional methods. Semiempirical calculations have been carried out on the keto-enol tautomerism of triazolopyrimidines.631 A base-catalysed keto-enol tautomer-ism has been proposed632 to be responsible for the observed deuterium exchange of the hydrogens at the 3-position of diazepam when the molecule is treated with alkaline deuteriated methanol. 

Diallenylsulfone (76) and the thiophene dioxide (77) are intermediates in the base-catalysed conversion of bis(y-alkenylpropargyl)sulfones (75) to the corresponding dihydrothiophene dioxides (78). The slowest step in the multistep process is the propargyl to allenyl tautomerization.181... 

Fig. Base-catalysed mechanism for keto-enol tautomerism.

Acid-catalysed hydrogen-deuterium exchange in norcamphor has also been investigated by Werstiuk and Banerjee (1977) (DOAc—D20—DC1 medium). It was observed that exo-deuteron addition to the enol is also preferred, but with a slightly smaller selectivity (x 190). This would mean that, if torsional factors cause preferential base-catalysed exo-exchange, they also occur for acid-catalysed keto-enol tautomerism. However, the absence of important torsional strain effects on the rate constants of acid-catalysed enolisation of cyclic and bicyclic ketones contradicts this assumption. 

Unfortunately, this requirement for the presence of aqueous base may well represent a strong limitation to the use of supported gold catalysts, as various base catalysed side reactions such as keto-enol tautomerism or oxidative decarbonylation could diminish selectivities. 

Carbonyl (or keto) compounds are interconvertible with their corresponding enols. This rapid interconversion of structural isomers under ordinary conditions is known as tautomerism. Keto-enol tautomerism is catalysed by acids or bases. 

Thiophen Analogues of Indene.—Quantitative data for the base-catalysed tautomerization of the 4-methyl- to the 6-methyl-4 T-cyclopenta[c]thipphen have been obtained. The tautomerization was about 10 times slower than that of 1-methylindene. 107f-Indeno[l,2-Z>][l]benzothiophen has been prepared by treating 2-phenylbenzo[6]thiophen-3-carboxaldehyde with sodium methoxide in hot bis(2-methoxyethyl) ether. ... 

A mechanistic study of acetophenone keto-enol tautomerism has been reported, and intramolecular and external factors determining the enol-enol equilibria in the cw-enol forms of 1,3-dicarbonyl compounds have been analysed. The effects of substituents, solvents, concentration, and temperature on the tautomerization of ethyl 3-oxobutyrate and its 2-alkyl derivatives have been studied, and the keto-enol tautomerism of mono-substituted phenylpyruvic acids has been investigated. Equilibrium constants have been measured for the keto-enol tautomers of 2-, 3- and 4-phenylacetylpyridines in aqueous solution. A procedure has been developed for the acylation of phosphoryl- and thiophosphoryl-acetonitriles under phase-transfer catalysis conditions, and the keto-enol tautomerism of the resulting phosphoryl(thiophosphoryl)-substituted acylacetonitriles has been studied. The equilibrium (388) (389) has been catalysed by acid, base and by iron(III). Whereas... 

Scheme 5.21 also shows the three pathways for keto enol tautomerization which, depending on pH, are catalysed by acid or base. The uncatalysed pathway is attributed to... 

The experimental basis of this theory is that many tautomeric changes that are catalysed by bases, say pyridine, do not occur in the presence of pyridine in a solvent that has been freed from impurities that might function as acids, but do occur when acidic im purities are present. The most striking example is the mutarota-tion of tetramethylglucose which is brought about by tautomeric... 

The experiments conclusively prove that the addition of hydrogen to C-4 of the coenzyme occurs at the Si face of the Schiff base. Evidence has already been provided for the syn nature of the tautomeric process in the reaction catalysed by pyridoxamine-pyruvate aminotransferase [107]. If the same precedent is extended to aspartate aminotransferase it then follows that the bond to C that is formed and broken in this case must also be located on the Si face at C-4, in the catalytic complex, as shown in structure 2 (Fig. 53). In other words, the alternative arrangement for syn proton transfer shown in 1 (Fig. 53) is precluded by these experiments. The direction of hydrogen addition to C-4 of the coenzyme in the half-reaction has also been studied using several other L-amino add requiring aminotransferases and in every case the medium hydrogen was shown to add to the Si face at C-4 (Table 5). These experiments have led to the generaUsed view that in B -dependent reactions... 

For example, n-p-hydroxyphenylglydne, a key intermediate in the synthesis of semisynthetic cephalosporins and penicillins, is currently manufactured on a multi-thousand ton scale. The hydantoinase-catalysed reaction is also suitable for the production of unnatural D-amino acids, although the in situ racemization of the remaining substrate via keto-enol tautomerization is generally slow. To facilitate the stereoinversion, base or hydantoin racemase of Pseudomonas and Arthrobacter strains is often used. 

A combination of a reversible reduction-oxidation system catalysed by iridium (see Scheme 5.28) and tautomerization of an aldehyde achieves a two-step racem-ization of a beta-chiral alcohol. This two-step racemization was applied to the DKR based on lipase-catalysed acylation using 2-phenylpropanal as a substrate (Scheme 5.21) [65]. 

We must now consider the kinetic analysis of catalysed reactions involving two proton transfers. These include the so-called prototropic isomerizations, notably keto-enol tautomerism. The simplest mechanisms for catalysis by acids and bases are as follows ... 

The complexes with hexadentate cage-like ligands result from tautomeric conversion of conjugated n systems of quadridentate macrocycles catalysed by bases due to the migration of protons of two secondary amino groups to y-carbon atoms, followed by coordination of the two C=N groups produced (Scheme 4-14). Poten-... 

Several papers have appeared on tautomerism in pyrimidines, including the parent molecule, pyrimidyl-2- and -4-cyanoacetic esters, and AT-substituted 4-aminopyrazolo[3,4-< ]pyrimidines. The last-mentioned system (5) is in equilibrium with (6) in aqueous solution. Interconversion is catalysed by acid and base, and proceeds via either an intermediate cation that is common to both neutral tautomers or through the anion. Other studies of condensed systems include... 

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