Structures of the Tautomers

In 1975, Weis and Mamaev153 showed that the 6-methyl-2,4-diphenyl dihydropyrimidine (MDHP) (20), which was obtained by condensation of benzylidene, acetone, and benzamidine, exists in solution in a tautomeric equilibrium of 6-methyl-2,4-diphenyl-1,4-dihydropyrimidine (20a) and 6-methyl-2,4-diphenyl-3,4-dihydropyrimidine (20b) [although the systematic nomenclature for structure 20b would be 4-methyl-2,6-diphenyl-1,6-dihy-dropyrimidine (see Section 111,8), we have retained the original nomenclature to provide a convenient comparison of the two tautomers]. This tautomerism was detected by spectral studies (NMR, IR, and UV) of solutions of 20. Thus the NMR spectra of the two individual tautomeric structures can be observed in dipolar aprotic solvents such as dimethyl sulfoxide (DMSO) and hexamethylphosphoramide (HMPA).153 

However, when the IR and UV spectra of 20 were recorded, using solid samples (KBr), only one tautomer was present, but the final assignment of its 

The combined X-ray, NMR, IR, and UV data enabled definite spectroscopic assignments for each of the tautomers of compound 20. Thus the IR vmax band at 1700 cm-1 was attributed to the stretching mode of the C=C— NH—C=N fragment of 20a, whereas the new band at 1645 cm-1, which appears in solution, is due to the C=C—N=C—NH fragment of 20b. The relative intensities of these absorption maxima, which depend on solvent polarity, give a qualitative estimate of the relative concentrations of each tautomer in a given solvent. 

Usefulness of IR and NMR data in assigning tautomer structure was further validated by structural elucidation of dihydropyrimidine 19 based on Silversmith s data.144 Its structure was assigned as the 1,6-tautomer 19b, based on a reinvestigation of its IR band at 1652 cm-1, similar to the IR spectra of 20b. This was later confirmed by X-ray analysis.23 

The infrared spectra of a series of these compounds were of particular interest. They showed a minimum of three important absorption bands at 1550-1620 (vc=c), 1600-1700 (vc=N), and 3200-3500 (vN H) cm-1. How- 

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The structures and energies of the tautomers of the bases of the nucleic acids have been subject to numerous computational studies. Since DNA is found in the aqueous environment of the cell interior, it is essential that the base tautomers, and the base pairs, be computed in the aqueous phase. In this section, we discuss the structures of the tautomers of each of the four DNA bases and uracil, found in RNA, focusing on the differences in the gas and solution phases. We then take on the structure of the base pairs in solution. 

Let us start the analysis of the influence of the hydration on the nonplanarity phenomena from the nonplanarity of the first type. There are two important observations here. First of all one may see that the nonplanarity of the first type (sp- hybradization of the amino group) does not depend significantly either on chemical structure of the tautomers or on the interaction with water molecules in the case of guanine and cytosine. 

T5993). Treatment of carboxylic acid 106 with thionyl chloride led to the formation of 107 via a cyclization and subsequent tautomerization of the furan ring the desired product 108 was not observed. The structure of the tautomer 107 was confirmed unambigously by X-ray crystallography. 

Complex tautomerism for azoles with heteroatoms in the 1,2-positions occurs for pyrazoles which are not substituted on nitrogen. Scheme 10 shows the four important tautomeric structures (148)-(151) for 3-methylpyrazolin-5-one, and (152) and (153) as examples of other possible structures. A detailed investigation of this system disclosed that in aqueous solution (polar medium) the importance of the tautomers is (149) > (151) (150) or (148), whereas in cyclohexane solution (non-polar medium) (151) > (148) (149) or (150). 

Figure 21 Structure of the most stable tautomers of difunctional pyrazoles...

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

The imbalance between and NMR studies in the solid state (Section VI,F) partly reflects the fact that it is easier to introduce N than into heterocyclic compounds, particularly azoles (DNMR in the solid state usually requires isotopic enrichment). Compared to solution studies, solid-state intermolecular proton transfer between tautomers has the enormous advantage that the structure of the species involved is precisely defined. 

Contributions in this section are important because they provide structural information (geometries, dipole moments, and rotational constants) of individual tautomers in the gas phase. The molecular structure and tautomer equilibrium of 1,2,3-triazole (20) has been determined by MW spectroscopy [88ACSA(A)500].This case is paradigmatic since it illustrates one of the limitations of this technique the sensitivity depends on the dipole moment and compounds without a permanent dipole are invisible for MW. In the case of 1,2,3-triazole, the dipole moments are 4.38 and 0.218 D for 20b and 20a, respectively. Hence the signals for 20a are very weak. Nevertheless, the relative abundance of the tautomers, estimated from intensity measurements, is 20b/20a 1 1000 at room temperature. The structural refinement of 20a was carried out based upon the electron diffraction data (Section V,D,4). 

Compound 6 crystallizes from cyclohexane as colorless needles which have no definite melting point there is a change of color to yellow at 128-134 C and the compound then melts sharply at 187-189 r C. When the colorless form is kept for a long time or recrystallized from pyridine or dimethyl sulfoxide it is changed into the yellow modification of mp 187-189 C recrystallization from cyclohexane reverses the process. It has been suggested that the yellow stable form has structure 6A and that the colorless metastable compound is the tautomer 2-methyl-l//-pyrido[2,3-6][l, 4]diazepin-4(5//)-one (6B). There is evidence from 1H NMR spectroscopy that the isomeric pyridodiazepin-2-one, yellow crystals, mp 195—197 " C, exists as an inseparable mixture of the tautomers 4-methyl-l//-pyrido[2,3-6][l,4]diazepin-2(3//)-one (7 A) and 4-methyl-l H-pyrido[2,3-6][l, 4Jdiazepin-2(5//)-one (7B) in the ratio 1 3. 

The structures of the a-D-aldo-pento and -hexo-pyranose monosaccharides are shown in Pig. 1. In all cases, these sugars will be studied as the six-membered-ring tautomer, as shown. 

The occurrence of a 5a-C-centered tocopherol-derived radical 10, often called chromanol methide radical or chromanol methyl radical, had been postulated in literature dating back to the early days of vitamin E research,12 19 which have been cited or supposedly reconfirmed later (Fig. 6.5).8,20-22 In some accounts, radical structure 10 has been described in the literature as being a resonance form (canonic structure) of the tocopheroxyl radical, which of course is inaccurate. If indeed existing, radical 10 represents a tautomer of tocopheroxyl radical 2, being formed by achemical reaction, namely, a 1,4-shift of one 5a-proton to the 6-oxygen, but not just by a shift of electrons as in the case of resonance structures (Fig. 6.5). In all accounts mentioning... 

One qualitative result of particular interest arises in the study of 3-hydroxypyrazole. The electronic structure of the oxo tautomer 8 may be thought of as having two mesomeric (i.e., resonance) contributors 8a and 8b, as illustrated... 

They also defined a state of metaionie in which no structural formula for the so-called tautomers corresponds to the "real" structure of the reacting molecule. The Kekule forms of benzene are examples of metaionie. 74... 

The aminomethylenemalonates (1 and 2) may exist in imine or enamine tautomeric forms of R1 or R2 is a hydrogen atom. In some early papers, the imine tautomer (see below) was given for the structure of the products, usually without any explanation or evidence (e.g., 1885CB319 37JCS867 49JIC171 88KGS931). 

The most powerful method currently available for the quantitative determination of ring-chain equilibrium constants is H-NMR spectroscopy. Often, two pairs of indicator signals of both tautomeric forms have been used, thereljy increasing the accuracy of equilibrium-constant determination. For structural analysis of the tautomers and quantitative measure-... 

SB. Actually, these tautomeric equilibria are more complex because each of these three forms can exist as two geometric isomers ( and Z for 75A and 75A) or two conformers (rotamers E and Z for 75B). When + H, two diastereomers cis and trans and R ) are possible for the cyclic tautomer 75B. These equilibria have been thoroughly investigated (88TH2) by means of electronic, IR, H-, and C-NMR spectroscopy. The structure of the solid 5-hydroxypyrazoline 74B- (R = Me R = H R = Ph R" = i-Pr) was confirmed by X-ray diffraction (87MI5). An approximate generalization of the influence of the structural factor on these equilibria is shown in Table X. 

The literature listed in Table 2 gives numerous examples of calculated bond lengths and angles with optimized geometry for the tetrazole tautomers. The electronic structures of the substituted 4,5-dihydrotetrazoles (14) have been investigated by MNDO and AM 1 calculations to explain their photoelectron spectra <88CB1213>. Their electronic structure resembles that of the c -2-tetrazene group and is characterized by three occupied n molecular orbitals and two n molecular... 

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