Proton tautomerism

Clearly, in the case of (66) two amide tautomers (72) and (73) are possible, but if both hydroxyl protons tautomerize to the nitrogen atoms one amide bond then becomes formally cross-conjugated and its normal resonance stabilization is not developed (c/. 74). Indeed, part of the driving force for the reactions may come from this feature, since once the cycloaddition (of 72 or 73) has occurred the double bond shift results in an intermediate imidic acid which should rapidly tautomerize. In addition, literature precedent suggests that betaines such as (74) may also be present and clearly this opens avenues for alternative mechanistic pathways. 

Fig. 1. Combined proton tautomerism and 90° rotation of porphyrin molecule in the solid state, (a) Reduced scheme proposed by Frydman et al. (89JA7001). (b) Complete scheme according to Limbach et al. (94JA6593).

At its best, the study of solvent kies by the formalism given can be used to learn about proton content and activation in the transition state. For this reason it is known as the proton inventory technique. The kinetics of decay of the lowest-energy electronic excited state of 7-azaindole illustrates the technique.25 Laser flash photolysis techniques (Section 11.6) were used to evaluate the rate constant for this very fast reaction. From the results it was suggested that, in alcohol, a double-proton tautomerism was mediated by a single molecule of solvent such that only two protons are involved in the transition state. In water, on the other hand, the excited state tautomerism is frustrated such that two water molecules may play separate roles. Diagrams for possible transition states that can be suggested from the data are shown, where of course any of the H s might be D s. 

Khandogin J, Brooks CL III (2005) Constant pH molecular dynamics with proton tautomerism. Biophys J 89 141-157. 

We now turn to the question of sensitivity of chemical constitution to crystal-field effects. Here the distribution of the various possible species in a system will be determined by bond-breaking and -forming processes. Except for the case of proton tautomerism, which we will treat at the end of this section, these processes are of high energy. Nevertheless, a variety of systems showing such sensitivity have been encountered. 

On benzene and some other aromatic systems, the donor or acceptor nature of a substituent is critical for the MCD sign, whereas on others such as pyridine it is not, at least for weak substituents. Further, the MCD is helpful for the analysis of a wide field of chemical events such as conformational changes coupled with substitutions, proton tautomerism, proton dissociation on aromatics, or through-space interaction in bicyclic aromatic systems 299-318>. 

As with 5-alkyl-l,2,4-triazin-3-ones, so also 5-alkyl-l,2,4-triazine-3-thiones (42) display proton tautomerism between the alkyl group and a ring nitrogen, as shown by H NMR spectroscopy (68TL2747). 

Photochromism and thermochromism derived from proton tautomerism. 244... 

Dielectric properties derived from proton tautomerism in crystals. 252... 

Step 3 Removal and replacement of a proton (tautomerism) leads to the amide. 

There are some additional possibilities for proton tautomerism with adenine, guanine, and cytosine (Fig. 15.5), where one of the protons can move from one ring nitrogen atom to another one. This type of tautomerism is restricted to the free bases and cannot occur in the nucleosides where pyrimidine N(l) and purine N(9) are substituted by the furanose moiety. 

MNDO, AMI, and PM3 study (with full geometry optimization, in the gas and aqueous phases) of the protonation tautomerization and valence tautomerization equilibria of some pyrrole macromolecules is described in the work <2002JMT(589)43>. 

The aim of this review is to describe the essence of proton tautomerism, focusing on the potential profile of proton transfer along the reaction coordinate of the tautomerization in the solid state. In Section 2, proton tautomerism in an isolated system is discussed based on spectroscopic... 

Before describing the physical properties derived from proton tautomerism in the solid state, the intrinsic nature of proton tautomerism in isolated systems, such as in the gas phase or in a dilute solution, is discussed. 

Fig. 13 Co-rotating model of the proton tautomerism of porphine [18] combination of proton transfer and 90° rotation.

This section describes the characteristics of the photo- and thermochromism derived from proton tautomerization in crystals, using the photo- and thermochromic behaviour of 2-alkylisophthalaldehydes, salicylideneanilines, and dinitrobenzylpyridines as typical examples. 

From the viewpoint of the dielectric properties of organic molecular crystals, the proton tautomerism of the s-cis form of 3-hydroxyenone [40] is intriguing, because the horizontal component of the dipole moment of a tautomeric... 

The mechanism of the polarity inversion of tautomeric molecules is totally different from the orientation polarization of conventional organic dielectrics, such as camphor and poly(vinylidene fluoride), and the dielectric response of this new type of dielectric should be much faster. Furthermore, a significant contribution of the proton-tunnelling mechanism to the proton tautomerism is frequently observed. Consequently, the dielectric property derived from proton tautomerization should have a high chance of being related to quantum phenomena. 

Since the proton tautomerism of naphthazarin [13] or 9-hydroxy-phenalenone [6] can be investigated precisely in an isolated system, it is intriguing to see how these tautomeric molecules behave as dielectrics in the solid state. Incidentally, if the tautomers keep the centrosymmetry during the tautomerization process, the dielectric response cannot be detected, because the changing directions of the dipole moments coupled with the tautomerization, even though they invert, cancel. 

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