Molecular-orbital calculations tautomerism

Hydroxypyridine 1-oxide is insoluble in chloroform and other suitable solvents, and, although the solid-state infrared spectrum indicates that strong intermolecular hydrogen bonding occurs, no additional structural conclusions could be reached. Jaffe has attempted to deduce the structure of 4-hydroxypyridine 1-oxide using the Hammett equation and molecular orbital calculations. This tautomeric compound reacts with diazomethane to give both the 1- and 4-methoxy derivatives, " and the relation of its structure to other chemical reactions has been discussed by Hayashi. ... 

According to a molecular orbital calculation of Veber and Lwowski, isoindole should be favored over its tautomer, isoindolenine, by about 8 kcal/mole. However, the calculated electronic distribution is markedly different in the two oases, particularly at position 1, and it is to be expected that the nature and pattern of substituents will play an important role in determining the position of tautomeric equilibrium between these two species. 

Two independent molecular orbital calculations (HMO method) of delocalization energies for isoindole and isoindolenine tautomers agree that the isoindole form should possess the more resonance stabilization. The actual difference calculated for isoindole-isoindolenine is about 8 kcal/mole, but increases in favor of the isoindole with phenyl substitution at position 1 (Table VI).Since isoindole and isoindolenine tautomers have roughly comparable thermodynamic stabilities, the tautomeric proce.ss is readily obser-... 

Most electrophilic substitutions in benzimidazole (31 R = H) occur primarily in the 5-position. In multiple bromination the order followed, 5 > 7 > 6,4 > 2, parallels molecular orbital calculations. In benzimidazole itself the 4(7)- and 5(6)-positions are tautomerically equivalent. Fusion of a benzene ring deactivates C-2 to electrophilic attack to such an extent that it is around 5000 times less reactive than the 2-position of imidazole. Strong electron donors at C-5 direct halogenation to the 4-position, whereas electron-withdrawing groups favor C-4 or C-6 substitution (84MI21). 

These authors conclude that the problem of internal solvation is still an experimental and theoretical challenge GB measurements for this type of molecules of low volatility are not always in good agreement194. Molecular orbital calculations may help to solve the difficult experimental problems, but they have to take into account conformational isomerisms and the prototropic tautomerisms of the amidine and guanidine moieties. In light of the above discussion, the proton affinities deduced from the experimental GB values should be based on accurate estimations of the entropy of cyclization 86. 

For more semi-empirical molecular orbital calculations and comparison with experimental data, see Section 4.01.2. For MO calculations on aromaticity and tautomerization, see Section 4.01.3. 

Naphthalene 1,2-oxide (136), a non-K-region epoxide, shows low thermal stability. Anthracene 1,2-oxide, on the other hand, is stable at ambient temperatures for several weeks. Preparation of (+ )-(lR,2S)-anthracene 1,2-oxide (137), using the above method, constitutes the first example of preparation of an optically pure arene oxide. However, the non-K-region oxides of phenanthrene, namely, its 1,2- and 3,4-oxides (47 and 48), obtained from chiral precursors, racemize fast.66 Perturbational molecular orbital calculations indicate that epoxide-oxepin valence tautomerism is possible. However, the oxepin could not be detected by NMR. 

Studies of the tautomeric state of 1,2,4-thiadiazines have been more or less confined to the biologically active 1,2,4-benzothiadiazines. Ultraviolet spectroscopic studies suggest that the 4//-tautomer of 1,2,4-benzothiadiazines, e.g. 152, is preferred in ethanol (60JOC970) in alkali, the anion dominates. Extended Hiickel molecular orbital calculations (70MI2) and 13C-NMR studies (79T2151) confirm this view (Scheme 6). 

This reaction was extended to prepare 7-nitro- and 9-nitro derivatives of pyrido[l,2-a]pyrimidinone 119 (R = N02, R1 = H R = H, R1 = N02) when the appropriate starting material 118 was heated in boiling dichloro-methane in the presence of triethylamine or when it was stirred in aqueous sodium hydroxide at 20°C (92AJC1825) or treated with sodium azide in aqueous tetrahydrofuran (92AJC2037). Semiempirical molecular orbital calculations (AMI) indicated that the 2-hydroxy-4-oxo tautomeric forms 119 are more stable than the alternative 4-hydroxy-2-oxo tautomeric forms. 

Tautomerism has been observed for 2-(2 -pyridyl)indoles using NMR and UV-fluorescence techniques <1998JOG4055>. Molecular orbital calculations indicate that the indole is about 40 kcal mol more stable than its tautomer. 

Similarly, the reversal of the thermochemical stability order upon one-electron oxidation has been demonstrated theoretically and experimentally for several heteroatom substituted carbonyl/enol pairs, e.g. esters [52,53] and acids [54,55]. A recent detailed evaluation of the substituent effect by Heinrich, Frenking and Schwarz using ab initio molecular orbital calculations [56] is summarized in Table 3. Both a- and 7t-donors X stabilize the two cationic tautomeric forms, but with Ji-donating groups (X F, OH, NHj) the enol radical cations are much more stable than the corresponding keto ions. On the other hand, with c-donor/rt-withdrawing substituents this thermochemical preference is less pronounced and in the case X BeH the order of relative stabilities of ionic keto/enol pairs is even reverted. 

The structures of thio- and dithiocarboxylic acids have been studied extensively using IR, UV/Vis and NMR spectra, and molecular orbital calculations for many decades now [3, 7-9]. Thiocarboxylic acids are considered to exist as fast tautomeric equilibrium mixtures of thiol (I) and thioxo (II) forms... 

Similarly, tautomerism of 20 was studied by theoretical molecular orbital calculations with total and relative energies in the gas phase indicating that tautomers 20 and 21 are more stable than 22 and 23. The relative low stability and lower dipole moments of the latter pair should make 20 and 21 favored in aqueous media. Self-consistent reaction field calculations indicate 20 is more stable (9-12 kcal moP ) in water than 21 <1998H(48)1833>. 

The tautomeric equilibrium of 28 was studied in the gas phase using molecular orbital calculations following the ai initio method at the HE with the 6-31G basis set (HF/6-31G ). The tautomer 29 is quite unstable, whereas the keto form 28 is the most stable tautomer in the gas phase. Since the form 30 is more polar than the keto form, electrostatic stabilization in polar solvents or in the solid state could favor the OH tautomer, which is in agreement with experimental results <1999T12405>. 

CNDO molecular orbital calculations [11] were performed to calculate the 7t charge distribution in substituted anthraquinones. Geometry optimization through energy minimization was prohibited by the size of the anthraquinones, and thus standard molecular bond distances and angles [12] were employed. CNDO calculations were also performed on tautomeric structures of hydroxy-substituted anthraquinones and resonance structures of amino-substituted anthraquinones. 

---