Theoretical calculations tautomers

The comparison of the experimental mean values with the theoretically calculated ones for individual tautomers (Section 4.04.1.5.1) (76AHC(S1)1) or conformers (Section 4.04.1.4.3) has been used in the literature to determine equilibrium constants. Thus, the experimental value for l,l -thiocarbonylbis(pyrazole) (40) is 3.19 D and the vector sums of the simple group moments after addition of the extra mesomeric moments are shown in Figure 8. From these values Carlsson and Sandstrom (6SACS1655) concluded that conformation (40b) exerts the largest influence. 

Since the domain explored will always be a very small part of the possible cases of tautomerism, it is essential to have general rules for families of compounds, substituents, and solvents. This chemical approach is maintained in this chapter, although the importance of the calculations is recognized. The following discussion begins with calculation of tautomeric equilibrium constants, followed by the combined use of theoretical calculations and experimental results (an increasingly expanding field) and ends with the calculations of the mechanisms of proton transfer between tautomers. 

IR spectra in conjunction with theoretical calculations (B3LYP/6-31G ) indicate that the n /2ydro-(2-hydroxy-4-oxo-4//-pyrido[l, 2-n]pyrimidinium)-hydroxide form exists in solution and in the crystal, but the 2-hydroxy-4//-pyrido[l,2-n]pyrimidin-4-one tautomer dominates in the gas phase (00JCS(P2)2096). 

Benzotriazole can exist in two tautomeric forms, l-//-benzotriazole (6.46, R = H) and 2-/f-benzotriazole. If the aromatic ring contains a substituent, the 1- and 3-nitrogen atoms of the triazole are not equivalent, and therefore a 3-//-benzotri-azole derivative can also exist. The equilibrium between the 1 -H and 2-H tautomers of benzotriazoles is strongly on the side of the 1 -H tautomer, in contrast to triazole where the 2-H tautomer is dominant. Tomas et al. (1989) compared experimental data (enthalpies of solution, vaporization, sublimation, and solvation in water, methanol, and dimethylsulfoxide) with the results of ab initio theoretical calculations at the 6-31G level. 

For an understanding of many systems involved in biochemistry it is important to know details of their tautomeric and ionic equilibria. For example, moving a molecule from aqueous solution to a polar environment inside a receptor may result in a different tautomer dominating the equilibrium, with consequences for the activity. In this chapter we have outlined how theoretical calculations can be used to study these systems, with the all important solvent environment treated explicitly. 

G. A. Worth, P. M. King, and W. G. Richards, Theoretical calculation of tautomer equilibria in solution. (5-)-Methyl imidazole, Biochim. Biophys. Acta 993 134 (1989). 

Theoretical calculations for the dipole moment of the 1H- (la) and 4H-tautomers (lb) gave values for the IH-tautomer that were closely in agreement with the observed value of triazole, whereas the calculated values for the 4H-tautomer were much higher. Ab initio calculations made at the 6.3IG level gave a good agreement with the observed dipole moment of 2.7ID for 3,5 bis(trifluoro-methyl)triazole (see Section 4.02.4.5). 

Fig. 18. The carboxylaie-histidine-zinc triad represents indirect carboxylate-zinc interaction across bridging histidine. Both tautomers of histidine are observed, and the hydrogen bond stereochemistry with carboxylate (either aspartate or glutamate) is generally syn. Experimental results and theoretical calculations suggest that the carboxylate-histidine- zinc form may be in equilibrium with the carboxylic acid-histidinate- zinc form, as shown.

The spontaneous oxepin-benzene oxide isomerization proceeds in accordance with the Woodward-Hoffmann rules of orbital symmetry control and may thus be classified as an allowed thermal disrotatory electrocyclic reaction. A considerable amount of structural information about both oxepin and benzene oxide has been obtained from theoretical calculations using ab initio SCF and semiempirical (MINDO/3) MO calculations (80JA1255). Thus the oxepin ring was predicted to be either a flattened boat structure (MINDO/3) or a planar ring (SCF), indicative of a very low barrier to interconversion between boat conformations. Both methods of calculation indicated that the benzene oxide tautomer... 

Dithietanes 74 have been studied as appropriate sources for their valence tautomers 1,2-dithiones 75a, 75b (equation 79) and theoretical calculations have been carried... 

The gas-phase basicity (GB) of 3-thio-5-oxo 1, 5-thio-3-oxo 2, and 3,5-dithio 4 derivatives of 2,7-dimethyl-[l,2,4]-triazepine (Figure 1) has been measured by means of Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and complemented with theoretical calculations. The experimental FTICR results are discussed in Section 13.14.4.1.l(i). The structures and vibrational frequencies of all stable protonated tautomers and all transition states connecting them have been obtained by means of the B3LPY density functional method, together with 6-31G basis set expansion. The final energies were obtained at the B3LYP/6-311 + G(3df,-2p) level (2002JPC7383). 

Theoretical calculations depicted in Section 13.14.2.1.1 (i) were complemented with experimental measurements of UV-Vis spectroscopy to determine which of the different tautomers of 3,5-dithio-2,7-dimethyl-[l,2,4]-triazepine 4 (Figure 1) are present in different solvents and ambient conditions <2005SAA875>. The results showed that in nonpolar solvents (MeCN), the most stable tautomeric forms seem to be the dithione form 4 followed by the isomers 6 and 7. The experimental spectrum showed three parts the first was located between 350 and 450 nm, log e 2.72 at 400 nm and log 3.37 at 360 nm, and appears to be composed of one or two mt bands. The second part of the spectrum located between 250 and 350 nm was a jtjt band, log e 4.46 at 290 nm. The third region below 250 nm was composed of two 7t7t bands located ca. 230 and 210nm, log s 3.92 at 230 nm and log s 4.17 at 210nm, respectively. 

Theoretical calculations on the 3-H tautomer of l-hydroxy-4-phenyl-5-carboxylic acid 443 (R4 = Ph, R5 = COOH) have been performed using the B3LYP/6-31G(d) (2005RJOC591) method. 

Claramunt et al. [22] used a H and 13C NMR to study the tautomer-isim of omeprazole in solution. The tautomeric equilibrium constant, KT = 0.59 in tetrahydrofuran at 195 K, is in favor of the 6-methoxy tautomer. The assignment of the signals was made by comparison with its two N-methyl derivatives in acetone-d6 and through theoretical calculations of the absolute shieldings (GIAO/DFT/6-3111++G ). 

Theoretical calculations (B3LYP/6-31G ) indicated that in their 13C NMR spectra C(2) and C(9) carbons of anhydro-(2-hydroxy-4-oxo-4H-pyrido[ 1,2-a]pyrimidinium)hydroxide mesoionic forms appeared at significantly higher field (ca. 159-160 ppm and 115-116 ppm, respectively), than in the 2-hydroxy-4/7-pyrido[l,2-a]pyrimidin-4-one tautomers (ca. 169— 173 ppm and 130 ppm, respectively) (00JCS(P2)2096). C(8) carbon of mesoions (pyridine-)/ type carbon) appeared at lower field (144-146 ppm) than 6-C (140 ppm, pyridine-a type carbon), as is typical of pyridinium compounds. 

Unlike all the porphyrin isomers discussed above (including porphyrin itself), hemiporphycene 31 possesses two nonequivalent /ran.v-protonated tautomers, even in the case of symmetrical peripheral substitution. The two tautomers 31a-l (22H,24H) and 31a-2 (21/7,23//) were identified in the II NMR spectrum recorded at low temperatures, with a concentration ratio of 7 1. This was in agreement with theoretical calculations, which predicted a marginally higher energy for tautomer 31a-2. 

Leszczynski et al. have shown interest in comparing experimental (matrix isolation) and calculated (B3LYP) IR data (frequency and intensity) to discuss the tautomerism of benzo-annelated pyridonone, pyrazinone, and pyrimidinone (144-148). These equilibria were well reproduced by theoretical calculations carried out at the QCISD and QCISD(T) levels. The combined experimental and theoretical results reveal links between aromaticity and tautomerism. Moreover, a UV-induced phototautomeric reaction transforming the oxo forms into the hydroxy tautomers was observed for all (except 3-hydroxyisoquinoline) studied compounds [144], The interest of Leszczynski in problems related to tautomerism, aromaticity, and proton transfer is also apparent in a study of (lH-aza-hetero-2-ylidene)-acetaldehyde and 2-azahetero-2-yl-ethanol tautomeric pairs [145],... 

A time-dependent DFT method was utilized for calculating the electronic transition energies of a series of 5-aryl-NH-tetrazoles in solution, and the calculated absorption bands were compared with experimental data <2003CPH65>. However, Sadlej-Sosnowska et al. compared the theoretically calculated spectra of 2//-tautomcrs with the spectra measured in solutions where the prevalence of l //-tautomers was well known. 

Whatever be the difficulties in dealing satisfactorily with the problem of the lactam-lactim tautomerism in hydroxypurines, the predominance of the lactam tautomer granted, there remains the problem of the detailed structure of the most probable lactam form for each isomer. The problem is essentially that of the site of location of the imidazole proton. From that point of view forms 34-38 have to be considered for 2-hydroxypurine, forms 39—42 for 6-hydroxypurine (hypoxanthine), and forms 43-45 for 8-hydroxypurine. There are, in addition, some betaine tautomeric forms but these are probably of low stability and will not be considered further. Before describing the results of theoretical calculations, it may be useful to indicate that from the experimental point of view we may, in this respect, turn again for significant evidence to infrared spectroscopy... 

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