Carbonyl groups tautomers

The keto tautomer (211a) is involved in the high electrophilic reactivin-of the C-5 carbonyl group. Thus ring opening has been reported u ith various amino nucleophilic reagents. 

Hi) Pyrazole rings containing carbonyl groups In this subsection compounds with a pyrazole C—O bond will be discussed independently of their aromatic character. In solution the tautomers of pyrazolinones, e.g. (78a), (78b) and (78c), are easily identified by their IR spectra (Figure 18) (76AHC(Sl)l). 

Although the conversion of an aldehyde or a ketone to its enol tautomer is not generally a preparative procedure, the reactions do have their preparative aspects. If a full mole of base per mole of ketone is used, the enolate ion (10) is formed and can be isolated (see, e.g., 10-105). When enol ethers or esters are hydrolyzed, the enols initially formed immediately tautomerize to the aldehydes or ketones. In addition, the overall processes (forward plus reverse reactions) are often used for equilibration purposes. When an optically active compound in which the chirality is due to an asymmetric carbon a to a carbonyl group (as in 11) is treated with acid or base, racemization results. If there is another asymmetric center in the molecule. 

The carbonyl groups that participate in the alkyne-addition process have not been limited to those that can form enol tautomers. For example, amides have been used as nucleophiles in a one-pot reaction sequence for the preparation of 2,3-disubstituted furanopyridones using Pd catalysis (Equation (96)).343 Furopyridines have also been obtained from the reaction of iodopyridones with alkynes under Pd catalysis,344 and alkynyl pyrimidones have been converted into 2-substituted furanopyrimidones under the influence of an AgN03 catalyst.345... 

In 2-hydroxyfuran (Scheme 12), tautomerism always involves loss of aromatic stabilization, but the energy loss is far less here. Moreover, favorable interaction in the carbonyl tautomers offsets part of this loss, and the higher bond energy of the carbonyl group means that the carbonyl form is favored for... 

This enediol can be regarded as a common enol tautomer for two different keto structures. In other words, there are two ways in which this enediol can tautomerize back to a keto form, and the reaction thus appears to shift the position of the carbonyl group. The reaction is enzyme catalysed, which allows the normal equilibrium processes to be disturbed. 

Abstraction of a proton from solvent will thus ultimately result in production of the more favourable keto tautomer, and restoration of the carbonyl group. 

We have seen that 2- and 4-hydroxypyridines exist primarily in their tautomeric amide-like pyridone forms (see Section 11.4.3). This preference over the phenolic tautomer was related to these compounds still retaining their aromatic character, with further stabilization from the carbonyl group. 3-Hydroxypyridine cannot benefit from this additional stabilization. In contrast, 2-aminopyridine and 4-aminopyridine exist almost entirely as the amino... 

Table 11 summarizes the main results on the tautomerism of mono-hydroxy-, -mercapto-, -amino- and -methyl-azines and their benzo derivatives, in water. At first sight the equilibrium between 2-hydroxypyridine (71) and pyridin-2-one (72) is one between a benzenoid and a non-benzenoid molecule respectively (71a 72a). However, the pyridinone evidently has a continuous cyclic p- orbital system, containing six it- electrons, the usual aromatic count, if the carbonyl group contributes none. This assumption implies the formula (72b), from which by redistribution of electrons we arrive at (72c), which has the same benzenoid system as (71a). Further canonical forms (71b, 71c) can be drawn of (71) which correspond to the non-benzenoid forms of (72). The elusive property of aromaticity is therefore possessed by both tautomers, although not necessarily by both equally. When the carbonyl oxygen of (72) is replaced by less electronegative atoms, as in the imine tautomers of amino heterocycles, or the methylene tautomers of methyl derivatives, the tendency towards polarization in forms corresponding to (72b) and (72c) is considerably less, and the amino and methyl tautomers are therefore favoured in most instances. 

In the majority of dehydration reactions, heterocyclic compounds are formed, rather than carbocyclic compounds. Many possibilities for formation of carbocyclic compounds exist, but these are important only if (a) the heterocyclic or acyclic tautomers cannot undergo further elimination reactions, or (b) the conditions of reaction greatly favor the formation of an acyclic tautomer capable of affording only the carbocyclic compound. Both five- and six-membered carbocyclic compounds have been isolated, with reductic acid being the compound most frequently reported. Ring closure occurs by an inter-molecular, aldol reaction that involves the carbonyl group and an enolic structure. Many examples of these aldol reactions that lead to formation of carbocyclic rings have been studied.47 As both elimination and addition of a proton are involved, the reaction occurs in both acidic and basic solutions. As examples of the facility of this reaction, pyruvic acid condenses spontaneously to a dibasic acid at room temperature in dilute solution, and such 8-diketones as 29 readily cyclize to form cyclohexenones, presumably by way of 30, either in acid or base. 

A compound that includes a carbonyl group on the imidazoline ring is described as sedative. Treatment of the guanidyl substituted amino acid creatine (87-1) with hydrochloric acid results in cyclization to the iminoimidazolinone creatinine (87-2). Condensation of that intermediate with meta-chlorophenylisocyanate (87-3) leads to the formation of a urea by condensation of the reactive function with the imidazole as its amino tautomer. There is thus obtained fenobam (87-4) [92]. 

The second main aspect of reactions of carbonyl compounds is one we have already touched upon in Chapter 3. The carbonyl group increases the acidity of C—H bonds on a carbon directly attached to it by many powers of ten over an unactivated carbon-hydrogen bond. Removal of such a proton leaves the conjugated ambident enolate ion (29), which can be reprotonated either at the carbon, to give back the original keto tautomer, or at oxygen to give the enol (Equation 8.61).135 Acid also promotes interconversion between enol and keto... 

The 9-formyl- and 9-benzoyltetrahydro-47/-pyrido[l,2-a]pyrimidin-4-ones derivatives exist predominantly as the 1,6,7,8-tetrahydro tautomer stabilized by an internal hydrogen bridge between N(l) and the 9-carbonyl group [83JCS(P2)1153 85JHC593]. 

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