Tautomerism and isomerization

Oxidation of 3-methoxycarbonyl-A -pyrazoline with lead tetraacetate yield a complex mixture of compounds amongst them the A, A -derivative (161). 

Pyrazolines have been used as models of intramolecular dyotropy by Mackenzie et al. 87T598i, 93JCS(P2)i2ii . In a series of beautiful experiments, which combine primary deuterium kinetic isotope effects and x-ray crystallography, Mackenzie shows that in convenient polycyclic systems, like (162) there is a double proton transfer to (163) which take place by simple heating (for instance, melting). 

Transformation of A -pyrazolines bearing a benzenesulfonyl group at position 3 occurs to give pyrazoles by reaction with KOH/MeOH with loss of the S02Ph group 92T8101 . 

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Infrared spectra were used for investigations on tautomerism and isomerism. The frequencies of the carbonyl stretching bands seem to depend on mesomerism and inductive effects with respect to the positions of the carbonyl group and the substituents at the triazolopyrimidine system [77HC(30)179]. 

Tautomerism and Isomerism Syntheses of the Pyrazole Ring General Reactions of Pyrazole Compounds Chemistry of Pyrazole Compounds Introduction [to Reduced Pyrazoles] Pyrazoline Syntheses Chemistry of the Pyrazolines Pyrazolidine Chemistry... 

The interactions of the electron spin S with the spins of the nuclei In and an external magnetic field B lead to the EPR spectmm [748-750]. Due to the sensitivities of the connected parameters it presents an important tool to obtain information about the geometrical arrangements, the electronic stmcture (e.g. spin distribution) and tautomeric and isomeric forms of a radical under consideration. However, since the relations are not clear-cut, such information can only be gained from investigations in which theory and experiment closely interact. An overview of different aspects of modem EPR spectroscopy offers a recent themed issue in PCCP [751]. 

Fast transient studies are largely focused on elementary kinetic processes in atoms and molecules, i.e., on unimolecular and bimolecular reactions with first and second order kinetics, respectively (although confonnational heterogeneity in macromolecules may lead to the observation of more complicated unimolecular kinetics). Examples of fast thennally activated unimolecular processes include dissociation reactions in molecules as simple as diatomics, and isomerization and tautomerization reactions in polyatomic molecules. A very rough estimate of the minimum time scale required for an elementary unimolecular reaction may be obtained from the Arrhenius expression for the reaction rate constant, k = A. The quantity /cg T//i from transition state theory provides... 

Tautomerism has been discussed in Section 4.04.1.5.2. It concerns prototropic tautomerism and the decreasing order of stability is (hydrazone) >A (azo)> A (enehydrazine). The isomerization A -> A occurs via a A -pyrazoline (65BSF769). Pyrazolidones and amino-A -pyrazolines exist as such. The only example of non-prototropic tautomerism deals with the isomerization (403) —> (404) (74CJC3474). This intramolecular process is another example (Section 4.04.1.5) of the thermodynamic analogy between prototropy and metallotropy. 

The same arguments can be applied to other energetically facile interconversions of two potential reactants. For example, many organic molecules undergo rapid proton shifts (tautomerism), and the chemical reactivity of the two isomers may be quite different It is not valid, however, to deduce the ratio of two tautomers on the basis of subsequent reactions that have activation energies greater than that of the tautomerism. Just as in the case of conformational isomerism, the ratio of products formed in subsequent reactions will not be controlled by the position of the facile equilibrium. 

Nuclear magnetic resonance spectra of all four parent compounds have been measured and analyzed.The powerful potentialities of NMR as a tool in the study of covalent hydration, tautomerism, or protonation have, however, as yet received no consideration for the pyridopyrimidines. NMR spectra have been used to distinguish between pyrido[3,2-d]pyrimidines. and isomeric N-bridgehead compounds such as pyrimido[l,2- ]pyrimidines and in several other structural assignments (cf. 74 and 75). 

Tautomers are defined as isomers which are readily interconvertible. It is clear that the distinction between tautomerism and ordinary isomerism is very vague indeed, and that it depends on the interpretation of the adverb readily. It is customary to designate as tautomers those isomers whose half-lives (with respect to interconversion) are under ordinary circumstances less than the times required for laboratory operations to be carried out (some minutes or hours), so that the separation of the isomers from the equilibrium mixtures is difficult. The distinction between tautomers and ordinary isomers has no molecular significance whatever, since it is dependent on the accidental ordinary rate of human activity. 

Recently, the hydroxy derivatives of furan, thiophene, and selenophene have been studied with regard to their physical properties and reactions. These compounds are tautomeric and if the oxygen function is placed in the 2-position they exist as unsaturated lactones and undergo carbon-carbon rearrangement, whereas the 3-hydroxy derivatives form oxo-enol tautomeric systems. By NMR the structures of the different tautomeric forms have been determined as well as the position of the tautomeric equilibrium and the rate of isomerization. 

Also termed ethyl acetoacetate, or CH3COCH2COOC2-H5. As an ester, it can be hydrolyzed under certain conditions to acetoacetic acid (CH3COCH2COOH) as a ketone, it reacts with reagents for the carbonyl (C = O) group. Peculiarly, it also behaves like a hydroxyl (OH-) compound. It is the prototype of the phenomenon of tautomerism, and its isomeric forms are termed the keto and the enol forms. 

Protonation of the alkyne produces the more favourable secondary vinyl cation, which is then attacked by water, since water is the predominant nucleophile available. Loss of a proton from this produces an enol, which is transformed into a more stable isomeric form, the ketone. This transformation is termed tautomerism, and we shall meet it... 

There is a distinct relationship between keto-enol tautomerism and the iminium-enamine interconversion it can be seen from the above scheme that enamines are actually nitrogen analogues of enols. Their chemical properties reflect this relationship. It also leads us to another reason why enamine formation is a property of secondary amines, whereas primary amines give imines with aldehydes and ketones (see Section 7.7.1). Enamines from primary amines would undergo rapid conversion into the more stable imine tautomers (compare enol and keto tautomers) this isomerization cannot occur with enamines from secondary amines, and such enamines are, therefore, stable. 

Of particular interest is the syn-l,6-imino-8,13-methano[14]annulene (59) which represents the first authenticated example of a stable 1H-azepine with a free NH group (80AG(E)1015). The annulene with aluminum oxide undergoes a remarkable isomerization to the anti isomer (61). Investigation shows that the isomerization is not a thermal reaction but involves alumina-catalyzed proto tropic shifts via the 3/7-azepine tautomer (60). This system is unique in that it is the first example of a 3H -> 1H azepine tautomerism, and is a consequence of the high degree of strain in the anti-Bredt 3iT-azepine (60). 

If, on the other hand, the resonance integral is very small, it may be convenient to refer to the substance as containing tautomeric or isomeric molecules, with electronic structures that are represented essentially by I or II alone. The relation of resonance to tautornerism and the distinction between tautornerism and isomerism are discussed in the last chapter of this book. 

Compounds which exhibit photochromism are classified according to the mode of their photochromic reaction, because changes in colour can arise as a result of heterolytic cleavage, homolytic cleavage, isomerization, tautomerization and oxidation. 

Often more complex situations arise in which additional tautomers or other forms arise via pH-independent reactions. These can all be related back to the reference ionic species by additional ratios R, which may describe equilibria for tautomerization, hydration, isomerization, etc. (Eq. 6-82).76 In the case illustrated, only one of the ratios, namely R2 or R3, is likely to be a tautomerization constant because, as a rule, H2P and P will not have tautomers. Equations analogous to Eqs. 6-76 to 6-82 can be written easily to derive Kc, K0 and any other microscopic constants desired from the stoichiometric constants plus the ratios R, to R4. While it is easy to describe tautomerism by equations such as Eqs. 6-76 and 6-82 it is often difficult... 

Enols are isomers of molecules containing C=0 double bonds. Both isomers equilibrate, and even small amounts of acid or base serve as a catalyst. The mechanism of acid-catalyzed iso-merizations will be presented Figure 12.4. Isomers existing in a dynamic equilibrium of this kind are referred to as tautomers the respective isomerism is termed tautomerism, and the isomerization of tautomers is called tautomerization. 

Enols tend to be unstable and isomerize to the ketone form. As shown next, this isomerization involves the shift of a proton and a double bond. The (boxed) hydroxyl proton is lost, and a proton is regained at the methyl position, while the pi bond shifts from the C = C position to the C=O position. This type of rapid equilibrium is called a tautomerism. The one shown is the keto-enol tautomerism, which is covered in more detail in Chapter 22. The keto form usually predominates. 

This type of isomerization, occurring by the migration of a proton and the movement of a double bond, is called tautomerism, and the isomers that interconvert are called tautomers. Don t confuse tautomers with resonance forms. Tautomers are true isomers (different compounds) with their atoms arranged differently. Under the right circumstances, with no catalyst present, either individual tautomeric form may be isolated. Resonance forms are different representations of the same structure, with all the atoms in the same places, showing how the electrons are delocalized. 

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