Tautomerism acid-catalysed

The reaction shows a first-order dependence on substrate concentration but, except at very low concentration, is zero-order with respect to oxidant moreover, the zero-order rate coefficient is the same as that observed with oxidations by iodine, cupric chloride and silver nitrate. The reaction is acid-catalysed. The oxidation is completely analogous to the halogenation of ketones and involves a slow tautomeric equilibrium followed by rapid oxidation, viz. 

Enolization and ketonization kinetics and equilibrium constants have been reported for phenylacetylpyridines (85a), and their enol tautomers (85b), together with estimates of the stability of a third type of tautomer, the zwitterion (85c). The latter provides a nitrogen protonation route for the keto-enol tautomerization. The two alternative acid-catalysed routes for enolization, i.e. O- versus Af-protonation, are assessed in terms of pK differences, and of equilibrium proton-activating factors which measure the C-H acidifying effects of the binding of a proton catalyst at oxygen or at nitrogen. 

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... 

The amino groups are replaced with oxygen. Although here a biochemical reaction, the same can be achieved under acid-catalysed hydrolytic conditions, and resembles the nucleophilic substitution on pyrimidines (see Section 11.6.1). The first-formed hydroxy derivative would then tautomerize to the carbonyl structure. In the case of guanine, the product is xanthine, whereas adenine leads to hypoxanthine. The latter compound is also converted into xanthine by an oxidizing enzyme, xanthine oxidase. This enzyme also oxidizes xanthine at C-8, giving uric acid. 

Internal alkynes undergo acid-catalysed addition of water in the same way as alkenes, except that the product is an enol. Enols are unstable, and tautomer-ize readily to the more stable keto form. Thus, enols are always in equilibrium with their keto forms. This is an example of keto-enol tautomerism. 

Fig. Acid-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. 

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. 

Methoxy- and 2-acetoxy-furans are available from 2,5-dimethoxy- and 2,5-diacetoxy-2,5-dihydro-furans (18.1.1.4) via acid-catalysed elimination. They undergo Diels-Alder cycloadditions the adducts can be further transformed into benzenoid compounds by acid-catalysed opening. 3,4-Dihydroxyfuran is undetectable in tautomeric equilibria between mono-enol and dicarbonyl forms the dimethyl ether behaves as a normal furan, undergoing easy a-electrophilic substitution, mono- or dilithiation at the a-position(s), and Diels-Alder cycloadditions. 2,5-Bis(trimethylsilyloxy)furan is synthesised from succinic anhydride it too undergoes Diels-Alder additions readily. Both furan-2- and -3-thiols can be obtained by reaction of lithiated furans with sulfur in each case the predominant tautomer is the thiol form. ... 

A further study, by the same workers, using the cyclic enones 199 ( = 1 or 2) showed that the addition occurs regioselectively across the carbonyl group ". The addition of phenylphosphonous acid (through its tautomeric phosphinic acid form) to 189 (R = Me, R = Ph) occurs in boiling benzene to give the dihydro-l,2-oxa-4-phosph(V)olene 201 (R = Me), produced by acid-catalysed cyclization within 200. When R = Ph, a linear product (202) is the result of 1,4-addition, and is again accompanied by the product 201 (R = Ph) of the cyclization of the l,2-adduct ... 

The oxygen-substituted 1,3-azoles exist in their carbonyl tautomeric forms. That there is little aromatic character left in such systems is nicely illustrated by the acid-catalysed dimerisation of imidazol-2-one, which acts as an enamide in the process. 

A full paper describes the photoaddition of N-nitrosopiperidine to cyclo-octa-1,5-diene. An intermediate adduct (57), after tautomerization, can undergo acid-catalysed cyclization to give bridged hydroxylamines (58). Adducts with nitrosyl chloride have similarly been reported, and evidence of the formation of bridged nitroxides has been given. Photodecomposition of the AT-chloro-amide... 

Actually, a diol is not formed. The intermediate (an enol) undergoes acid-catalysed rearrangement to give a ketone (Following fig.). This process is called a keto-enol tautomerism. 

The mechanism involves acid-catalysed conversion of the keto form of the cyclic P-diketone into the enol form, which is able to attack the protonated enone. The mechanistic detail is precisely analogous to the attack of an enolate the only difference is that both reactants are protonated. The product is the enol form of the triketone, which rapidly tautomerizes to the more stable keto form. 

Acid-catalysed dealkylation gave the corresponding dihydroxythiophen systems. The predominant tautomeric structure was determined by spectroscopic methods. 5-Substituted 2-cyano-3-hydroxythiophens, prepared through ring-closure reactions, were shown to exist as intramolecu-larly hydrogen-bonded hydroxy-forms. ... 

Another example of 1,3-thiazine formation is afforded by the acid-catalysed ring-opening and ring-closure of a 3,6-dihydro-2(li/)-pyrimi-dinethione to the isomeric 2-amino-4fr-l,3-thiazine thus, in hydrochloric acid solution the thione (32) is smoothly converted into (33), which appears to exist predominantly in the amino tautomeric form (u.v. and i.r. evidence). The sequence of reactions in Scheme 7 is suggested to account for the formation of (33). 

Potentially tautomeric pyrimidines and purines are /V-alkylated under two-phase conditions, using tetra-n-butylammonium bromide or Aliquat as the catalyst [75-77], Alkylation of, for example, uracil, thiamine, and cytosine yield the 1-mono-and 1,3-dialkylated derivatives [77-81]. Theobromine and other xanthines are alkylated at N1 and/or at N3, but adenine is preferentially alkylated at N9 (70-80%), with smaller amounts of the N3-alkylated derivative (20-25%), under the basic two-phase conditions [76]. These observations should be compared with the preferential alkylation at N3 under neutral conditions. The procedure is of importance in the derivatization of nucleic acids and it has been developed for the /V-alkylation of nucleosides and nucleotides using haloalkanes or trialkyl phosphates in the presence of tetra-n-butylammonium fluoride [80], Under analogous conditions, pyrimidine nucleosides are O-acylated [79]. The catalysed alkylation reactions have been extended to the glycosidation of pyrrolo[2,3-r/]pyrimidines, pyrrolo[3,2-c]pyridines, and pyrazolo[3,4-r/]pyrimidines (e.g. Scheme 5.20) [e.g. 82-88] as a route to potentially biologically active azapurine analogues. 

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... 

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. 

The hydroniumm ion-catalysed vinyl alcohol-acetaldehyde isomerization has been investigated627 via ab initio MO calculations, and the results have supported the stepwise mechanism shown in Scheme 125. A theoretical study of the tautomeric rearrangements in mono- and di-chalcogenide analogues of formic acid, [HC(X)YH ... 

It has been established that zinc-catalysed decarboxylation of (3-keto-acids involves a preliminary metal-promoted keto-enol tautomerism, as shown.272... 

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