Tautomerism conformation

As evidenced from x-ray data, azoniaallene cations (61) adopt the less sterically demanding allylium valence tautomeric conformation (19) in accordance with Wurthwein s calculations <84CB3365,84JOC297l> which predict that this is the more stable conformation for amino substituted azoniaallene cations (Equation (1)). 

In the next chapter by Ibon Alkorta and Jose Elguero, applying computational approaches presents interrelations between aromaticity and chemical and physicochemical properties of heterocycles. The following problems and properties are considered tautomerism, conformation analysis, acid-base equilibria, H-bonding and proton transfer, energetics, reactivity, IR-, NMR-, and MW-spectroscopies. At the end is a discussion of problems related to supramolecules and macrocycles. 

A quantitative description of the influence of the solvent on the position of chemical equilibria by means of physical or empirical parameters of solvent polarity is only possible in favourable and simple cases due to the complexity of intermolecular solute/solvent interactions. However, much progress has recently been made in theoretical calculations of solvation enthalpies of solutes that can participate as reaction partners in chemical equilibria see the end of Section 2.3 and references [355-364] to Chapter 2. If the solvation enthalpies of all participants in a chemical equilibrium reaction carried out in solvents of different polarity are known, then the solvent influence on this equilibrium can be quantifled. A compilation of about a hundred examples of the application of continuum solvation models to acid/base, tautomeric, conformational, and other equilibria can be found in reference [231]. 

Durant and coworkers used FEP (BOSS 3.1) and ab initio 6-31G (Gaussian 90) calculations to determine the tautomeric/conformational equilibrium of histamine and (aR,pS)-aP-dimethylhistamine in neutral and proto-nated forms. The relative tautomerization free energy for the neutral species, tMc( e-N3H-histamine (g3H), tra s-N3H-histamine (t3H), and tra s-NlH-histamine (tlH) with respect to gawcfee-NlH-histamine (glH) was -1.94 0.19, -3.08 0.26, and -1.28 + 0.32 kcal/mol, respectively. The percentage in solution for neutral glH, g3H, t3H, and tlH was predicted to be 1%, 12%, 83%, and 4%, respectively. The authors concluded that the preference for t3H may be due to the large number of polar sites available for hydration. The relative tautomerization free energy for protonated t3H, tlH, and glH with... 

Theoretical study of the tautomeric/conformational equilibrium of aspartic acid zwitterions in aqueous solution "... 

Fig. 28 (a) The five more stable species of cytosine enol-amino trans (EAt), enol-amino cis (EAc), keto-amino (KA), keto-imino trans (Kit), keto-imino cis (KIc) given in order of stability according to MP2/6-311++G(d,p) ab initio calculations, (b) LA-MB-FTMW spectra for the li i-Oo,o rotational transition of the five species, (c) Theoretical simulation of the nuclear quadrupole hyperfine structure for the Iri-Oo o rotational transition. The differences among the various patterns act as fingerprints for tautomeric/conformational assignment. (From [169])... 

The use of molecular models gained special prominence in the middle of the 19th century as the chemical significance of three-dimensional molecular shape became recognized [Brock, 2000]. While such structures could be represented on paper, physical models gave an immediacy and an ease of visualization that sketches alone did not provide. They also provided a framework in which certain theoretical concepts such as steric hindrance, tautomerism, conformational changes, and chirality could be explored. Famously, the discovery of the double helical structme of DNA was aided by the manipulation of physical models, specifically with respect to the keto/eno tautomerism of the bases [Watson, 1968],... 

In cases of asymmetrically substituted heterocycles (see, e.g., [25,30,31,50,51]), the proton relocation modifies the dipole moment of the system, while the neutrality of the solute is preserved. Partition of the solute into a shghtly polar phase is generally more favorable with a smaller dipole moment. Thus, for a given molecule, the free energy changes in a solution through possible tau-tomeric/conformational transformations could be explored theoretically. Such studies would allow for the estimation of the tautomeric/conformational equilibrium constant in the selected solvents or miscible mixtures. However, from the point of view of the partition mechanism between the aqueous solution and a nonmixing solvent model of the lipophilic phase, interface studies are required, as mentioned above. 

The main appHcation of nmr in the field of pyrazolines is to determine the stereochemistry of the substituents and the conformation of the ring. For pyrazolones, nmr is useful in estabUshing the stmcture of the various tautomeric forms. Table 2 summarizes the chemical shifts of a few representative derivatives. 

Indolizine, hydroxy-conformations, 4, 451 GLC retention times, 4, 451 synthesis, 4, 121 tautomerism, 4, 198, 452 Indolizine, 2-hydroxy-synthesis, 4, 463 Indolizine, 8-hydroxy-conformation, 4, 452 Indolizine, 2-hydroxymethyl-synthesis, 4, 461 Indolizine, 3-hydroxymethyl-synthesis, 4, 461 Indolizine, 6-hydroxymethyl-synthesis, 4, 461 Indolizine, methyl-mass spectra, 4, 187, 450 NM 4, 448 Indolizine, 2-methyl-diazo coupling, 4, 454 mass spectra, 2, 529, 4, 450 nitration, 4, 50, 454 nitrosation, 4, 454 reaction with diaryl disulfide, 4, 460 reaction with nitroethane, 4, 460 Indolizine, 3-methyl-basicity, 4, 454 Indolizine, 5-methyl-acidity, 4, 461 synthesis, 4, 466 Indolizine, 6-methyl-mass spectra, 4, 450 Indolizine, l-methyl-2-phenyl-nitration, 4, 454 nitrosation, 4, 454, 455 Indolizine, 3-methyl-2-phenyl-reaction... 

Oxadiazine, tetrahydro-conformation, 3, 1054 ring-chain tautomerism, 3, 1056... 

Pyran-2-one, 5,6-dibromo-5,6-dihydro-reactions, 3, 735 Pyran-2-one, 5,6-dihydro-allylic bromination, 3, 799 dehydrogenation, 3, 724, 799 H NMR,3, 581 synthesis, 3, 841, 843 Pyran-2-one, 4,6-dimethyl-irradiation, 3, 677 photochemistry, 3, 678 Pyran-2-one, 5,6-dimethyl-chloromethylation, 3, 680 conformation, 3, 631 Pyran-2-one, 5-f ormyl-IR Spectra, 3, 595 Pyran-2-one, 6-formyl-IR spectra, 3, 595 Pyran-2-one, 5-halo-synthesis, 3, 799 Pyran-2-one, 3-hydroxy-IR spectra, 3, 595 Pyran-2-one, 4-hydroxy-methylation, 2, 57 3, 676 pyran-4-one synthesis from, 3, 816 reactions with phosphorus oxychloride, 2, 57 synthesis, 3, 792, 794, 795, 798 tautomerism, 2, 56 3, 642 Pyran-2-one, 4-hydroxy-6-methyl-methylation, 3, 692 reactions... 

Pyrazole, C-formyl-conformation, 5, 209 Pyrazole, fluoro-reactions, 5, 263, 267 Pyrazole, 4-fluoro-5-hydroxy-tautomerism, 5, 214 Pyrazole, 1-germyl-synthesis, 5, 236 Pyrazole, halo-halogenation by, 5, 54 reactions, 5, 104, 105, 266 reduction, S, 105, 106, 266 Pyrazole, 3-halo-1-phenyl-quaternary salts... 

N-alkylation, 4, 236 Pyrrole, 2-formyl-3,4-diiodo-synthesis, 4, 216 Pyrrole, 2-formyl-1-methyl-conformation, 4, 193 Pyrrole, 2-formyl-5-nitro-conformation, 4, 193 Pyrrole, furyl-rotamers, 4, 546 Pyrrole, 2-(2-furyl)-conformation, 4, 32 Pyrrole, 2-halo-reactions, 4, 78 Pyrrole, 3-halo-reactions, 4, 78 Pyrrole, 2-halomethyl-nucleophilic substitution, 4, 274 reactions, 4, 275 Pyrrole, hydroxy-synthesis, 4, 97 Pyrrole, 1-hydroxy-cycloaddition reactions, 4, 303 deoxygenation, 4, 304 synthesis, 4, 126, 363 tautomerism, 4, 35, 197 Pyrrole, 2-hydroxy-reactions, 4, 76 tautomerism, 4, 36, 198... 

Thiazolidine-2,4-dione, 2-dialkylamino-bisimide synthesis, 5, 129 Thiazolidine-2,4-diones IR spectroscopy, 6, 242 tautomerism, 6, 270 Thiazolidine-2,5-diones synthesis, 5, 138 Thiazolidine-4,5-diones synthesis, 5, 129 6, 316-317 Thiazolidine-2,4-dithiones tautomerism, 6, 270 Thiazolidines "C NMR, 6, 243 conformation, 6, 242, 247 dihydrothiazines from, 2, 93 hydrolysis, 6, 273 IR spectra, 6, 242 ring fission, 5, 80 synthesis, 5, 118 6, 316-321 Thiazolidines, imino-tautomerism, 6, 273 Thiazolidines, methyl-conformation, 6, 242 Thiazolidine-2-thione, 3-acyl-reduction, 1, 469 Thiazolidine-2-thione, 4-alkyl-synthesis, 6, 318... 

Thiazoline-2-thione, 3-(morpholinomethyl)-electrophilic substitution, 6, 290 4-Thiazoline-2-thione, 3,4,5-trialkyl-conformation, 6, 247 Thiazoline-2-thiones IR spectra, 6, 241 oxidation, 5, 103 reactions, 5, 102 2-Thiazoline-5-thiones tautomerism, 6, 249 4-Thiazoline-2-thiones... 

These cover the following topics (a) theoretical methods, with emphasis on the utility of such methods b) molecular dimensions, as determined by X-ray, electron diffraction and microwave spectra (c) molecular spectra, covering NMR, IR, UV, mass and photoelectron spectra [d) thermodynamic aspects, such as stability, ring strain, aromaticity, shape and conformation of saturated and partially saturated rings (c) tautomerism, including prototopic and ring-chain (/) betaine and other unusual structures. 

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. 

Uracil, thymine, and cytosine have been studied using this technique (89JA2308 and references therein). For uracil and thymine, the dioxo tautomer predominates in the case of cytosine (70), three tautomers were detected, 70a, 70b, and 70c, the last one being the least abundant. The gas-phase tautomeric equilibrium of 2-pyridone 15a and 2-hydroxypyridine 15b has been studied by MW spectroscopy (93JPC46) using both a conventional spectrometer and a jet-cooled millimeter-wave spectrometer. The relative abundances are 3 1 in favor of the hydroxy form 15b, which exists in the Z conformation shown (Scheme 23). 

The nonchelated structure that conforms to the hydroxy tautomeric form of the ligand 248a has been found in the hydrate 379 [96JOM(511)227]. 

No annular tautomeric equilibrium transformations in compounds of the diox-ane series have been reported yet recently (97JCC1392), however, the optimized geometries and total energies of unsubstituted isomeric 3,4-dihydro-1,2-dioxin 22 and 3,6-dihydro-1,2-dioxin 23 were calculated using ab initio 3-21G, 6-31G, and MP2/6-31G //6-31G methods. All the methods applied revealed that the total energies for half-chair conformations of 22 and 23 are approximately the same. 

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