Prototropie tautomerism

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. 

For 3-acetylthiotetronic acid the same type of tautomerization process (90 91, 92 93 as a result of prototropy between internal tautomers 90, 91 92, 93, rotation of the side-chain group, between external tautomers) was observed as for the corresponding 3-acetyl-tetronic acids ( H NMR, NMR) [76JHC533 78BCJ651 79JCS (P2)1605],... 

Annular prototropie tautomerism of 1,2,3-triazole (v-triazole) and its C-substituted derivatives involves the equilibrium of three possible isomers 24a-24c. In the ease of the parent eompound (R = H), 24a and 24c are degenerate isomers (Seheme 11). 

Tautomeric rearrangements of transition-metal complexes with azole ligands are relatively scarce. The fluxional behavior of the rhodium complex 43 with a neutral 3,5-dimethylpyrazole was explained as the result of rapid processes of metallotropy and prototropy occurring simultaneously (Scheme 24) [74JOM(C)51],... 

Dihydro-2/7- 74 and -4//-l,2-oxazines and thiazines 75 are interrelated by prototropy, being enamines and imines, respectively. In the case of oxazines, the imine form 75 is favored, and there are several well established examples of this system, including the parent heterocycle 75 (X = O) [84MI2]. No tautomeric equilibrium between the 2H and 4H forms has been observed under normal conditions in solution or in the solid state. However, the formation of intermediate 2H isomers 77 was proposed both for the conversion of 3-phenyl-5,6-dihydro-4//-l,2-oxazine 76 (R = Ph, r = R = H) into 2-phenylpyrrole(89TL3471) under strong basic conditions and for thermal decomposition of cyclopentene-fused 1,2-oxazine 76... 

Tautomerism, strictly defined, could be used to describe the reversible interconversion of isomers, in all cases and under all conditions. In practice, the term has increasingly been restricted to isomers that are fairly readily interconvertible, and that differ from each other only (a) in electron distribution, and (b) in the position of a relatively mobile atom or group. The mobile atom is, in the great majority of examples, hydrogen, and the phenomenon is then referred to as prototropy. Familiar examples are / -ketoesters, e.g. ethyl 2-ketobutano-ate (ethyl acetoacetate, 23), and aliphatic nitro compounds, e.g. nitro-methane (24) ... 

There are two important types of tautomerism found for small and large rings valence bond tautomerism and (to a somewhat lesser extent) annular prototropy. 

Prototropy in hydroxybenzopyranones has been investigated. The hydroxychromone (241) does not undergo tautomerism to the dione (242 equation 7). The NMR spectrum of a CDC13 solution shows the methyl signal at S 2.50 and since this appears as a singlet, it would seem that the contribution of (242) is not significant. Solid state and chloroform solution IR spectra also support this conclusion (71MI22201). 

There are various forms of tautomerism which operate in the different purine species. (1) Prototropy which involves attachment of the proton to any one of the four ring nitrogen atoms (Scheme 5). Corresponding CH tautomers, for example (52), seem to be of little significance. (2) Amine-imine tautomerism which operates in the aminopurines such as adenine (Scheme 6). (3) Lactam-lactim tautomerism as in the hydroxypurines such as hypoxanthine (Scheme 7) and the related thioxo-thiol tautomerism (53) and (54) in the biologically imporfant mercaptopurines (Scheme 8). The subject has recently been discussed in some detail <76AHC(Si)502>. 

The tautomerism of 1,2,4-triazoles (see Chapter 4.01 and (76AHC(S1)i)) may involve one or more of the following possibilities annular prototropy, prototropy involving both the ring and substituents and tautomerism restricted to the substituent. Only the first two of these will be considered. 

In A -unsubstituted triazoles (1 or 2 R R = H) prototropy between nuclear N centres may occur. When R and R are different, the equilibrium in Scheme 8 is not only of theoretical importance but may affect alkylation, acylation, prototropy between ring and substituents, ligand properties and so on. Most experimental and theoretical considerations favour IH (1) (or 2H (21)) as the predominant or only tautomer the 4H tautomer may play a comparable role. The paradox arises from the all too common oversimplification of the problem the tautomeric status of a given triazole need not be the same in solution, melt, solid or gas phase. Variation of substituents, solvents, temperature and the often ignored variation of energy input by different analytical methods provide a field of results rather than a unanimous decision for or against a certain tautomer. 

Prototropy in triazoles is particularly complex when substituents such as OH, SH and NHR are available to donate protons to annular N. A detailed discussion of all possible sub-cases of this type is beyond the scope of this chapter, but the main aspects of this matter are reviewed in a broad critical context (76ahc(s1)i. p. 388, 4i4, 444) tabulating generalizations and their levels of reliability. The section on reactivity (Section 4.12.3) gives examples of the variability of tautomeric preference in some reactions. 

Tautomerism and prototropy Chapter Elguero, Marzin, Katritzky and Linda 76AHC(S1)502... 

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