Prototropic tautomerization

For further details and examples of prototropic tautomerism in pyridazines and condensed pyridazines, see (63AHC(1)339, B-76MI21200). 

After the publication of a book on the prototropic tautomerism of aromatic heterocycles (76AHC(Sl)l) which covered the literature up to 1975, the study of the tautomerism of pyrazoles has not made great strides. In this section the main conclusions of this earlier review will be summarized and comments on a few recent and significant references added. 

An account of non-prototropic tautomerism (mainly annular metallotropy) and nonaromatic functional tautomerism will also be included. 

A well-known example of non-prototropic tautomerism is that of azolides (acylotropy). The acyl group migrates between the different heteroatoms and the most stable isomer (annular or functional) is obtained after equilibration. In indazoles both isomers are formed, but 2-acyl derivatives readily isomerize to the 1-substituted isomer. The first order kinetics of this isomerization have been studied by NMR spectroscopy (74TL4421). The same publication described an experiment (Scheme 8) that demonstrated the intermolecular character of the process, which has been called a dissociation-recombination process. 

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. 

Prototropic tautomerism of isoxazole derivatives has been well studied over a number of years and has recently been reviewed in context with similar behavior in other five-membered heterocycles (70C134, 76AHC(Sl)l, 79AHC(25)147, p. 202). Several generalizations are summarized below. 

Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

General accounts of prototropic tautomerism have been presented by Ingold and Baker" these include an outline of the historical development of the subject in which heteroaromatic compounds are discussed incidentally, and, therefore, such a historical account will not be given here. Of historical interest are Eistert s book on tautomerism and mesomerism which was published in 1938, a review on — NH-CO— tautomerism by Arndt and Eistert published in 1938, and Heller s account of heterocyclic tautomerism which appeared in 1925. Although more recent works on heterocyclic chemistry (e.g., references 9-11) have dealt incidentally with tautomerism, no unified... 

Prototropic Tautomerism of Heteroaromatic Compounds I, General Discussion and Methods of Study... 

Prototropic Tautomerism of Heteroaromatic Compounds II. Six-Membered Rings... 

Prototropic Tautomerism of Heteroaromatic Compounds III. Five-Membered Rings and One Hetero Atom A. R. Katritzky and J. M. Lagowski... 

Prototropic Tautomerism of Heterparomatic Compounds IV. Five-Membered Rings with Two or More Hetero Atoms... 

The phenomenon of tautomerism comprises many different types of which the prototropic tautomerism that we consider here is only one. Prototropic tautomerism exists when the two tautomers differ only in the position of a proton (this is, of course, an approximation there are other differences between two tautomers, for example, in precise bond lengths). Other important types of tautomerism include the following (1) anioniotropy, where the two tautomers differ only in the position of an anion, which moves from one place to another in the molecule (2) cationiotropy, where the two tautomers differ in the position of a cation (other than a proton), which moves from one place to another in the molecule (3) ring-chain tautomerism and (4) bond-valence tautomerism. 

There has been some interest in comparing prototropic tautomerism to other equilibria where the migrating entity is not the proton. A significant... 

Prototropic tautomerism differs from all other types (methyltropy, metallotropy, acylotropy, halogenotropy, etc.) because the proton is very small, and therefore insensitive to steric effects, and also that it forms hydrogen bonds (HBs), which can considerably affect both the equilibrium and the rate of the process. 

Vibrational spectroscopy (IR and Raman, Section VII,B) is a field where theoretical calculations have revolutionized the method two groups have made essential contributions to prototropic tautomerism ... 

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