Three tautomerism

A-2-Thiazoline-4 one may exist in three tautomeric forms (174a. 174b. and 174c) (Scheme 90). 

A-2-Thiazoline-5-one may exist in three tautomeric forms (Scheme 108). The tautomeric equilibrium has been studied by H NMR (446. 453. 457. 464). infrared (453. 464-466). and ultraviolet (453, 464) spectros-... 

Together with pyridones, the tautomerism of pyrazolones has been studied most intensely and serves as a model for other work on tautomerism (76AHC(Sl)l). 1-Substituted pyrazolin-5-ones (78) can exist in three tautomeric forms, classically known as CH (78a), (DH (78b) and NH (78c). In the vapour phase the CH tautomer predominates and in the solid state there is a strongly H-bonded mixture of OH and HN tautomers (Section 4.04.1.3.1). However, most studies of the tautomerism of pyrazolones correspond to the determination of equilibrium constants in solution (see Figure 20). 

Aromatic pyrazoles and indazoles, in the broad sense defined in Sections 4.04.1.1.1 and 4.04.1.1.2, will be discussed here. Tautomerism has already been discussed (Section 4.04.1.5) and acid-base equilibria will be considered in Section 4.04.2.1.3. These two topics are closely related (Scheme 10) as a common anion (156a) or a common cation (156b) is generally involved in the mechanism of proton transfer (e.g. 78T2259). For aromatic pyrazoles with exocyclic conjugation there is also a common anion (157) for the three tautomeric forms... 

The position of the equilibrium is determined not only by ring size and polar and steric factors but also by the environment of the molecule. The experimental evidence for the existence of three tautomeric forms has been based on the study of their reactivity and, to a lesser degree, on physicochemical measurements 175-177). Often the existence of the corresponding carbinolamine or its acyclic tautomeric form in addition to the basic dehydrated form is quite important. 

However, a critical examination of the enormous amount of the experimental material that has piled up over more than 80 years leads to the conclusion that the three tautomeric forms postulated by Gada-mer have not been proven in one single case. The so-called evidence is based on chemical reactions, " which are noncompelling, or on physical constants that have been interpreted in a biased manner. For the simultaneous existence of both forms of the ring-chain proto-tropic system, i.e., the carbinolamine and the amino-aldehyde, evidence is available only for one single case. ... 

Monosubstituted hydrazones of isatin can exist in at least three tautomeric forms 124-126. According to spectroscopic data, only hydrazone 124 is present in solution (81JOC2764). 

The amino form 66a of 5-pyridylamino-l,2,4-triazole stabilized by two intramolecular hydrogen bonds is the only tautomer observed by the X-ray study of the crystal (90KGS1632). However in DMSO-dg, DMF-d7, and HMPA-di8 solutions, the equilibrium involves three tautomeric forms 66a-66c (Scheme 31) (90KGS1632). 

An amino group may take any of three possible positions in the five-membered isoxazole ring, giving rise to three tautomeric forms for 70 and 71 and four forms for 72 [76AHC(S1), pp. 416, 444, 445 84CHEC-I(5)1]. However, only amino structures 70a-72a have been detected using IR- or NMR-spectroscopic techniques (Scheme 33). 

As the alkaloid was extracted with hexane, acetone, and ethanol, subjected to column chromatography, acidified (AcOH) and then neutralized (NaOH), the cationic form was formulated as a hydroxide salt. However, only two OH groups were detectable on H NMR spectroscopy. Only slight differences were found in the UV spectra taken in methanol [kmax (loge) = 218 (4.68), 302 (4.39), 394 (4.08) nm] and methanol+NaOH [T-max (loge) = 228 (4.66), 310 (4.39) nm]. Three tautomeric forms can be formulated which are shown in Scheme 42. Two of them possess the isoquinolium-7-olate moiety. The H NMR data are presented in Table IV. They indeed unambiguously resemble the cationic species 112. 

These compounds can exist in the three tautomeric forms illustrated by structures 52-54, which will be referred to as the OH, CH, and... 

As early as 1895, Knorr realized that three types of derivatives could be formed for this type of compound, corresponding to the three tautomeric structures. Other early investigators assigned an 0X0 structure to these compounds on the basis of tenuous chemical evidence, while still others discussed the tautomerism without reaching any definite conclusions. ... 

The structural studies of isoxazol-5-ones have shown that these compounds can be found in one of the three tautomeric forms (45-47 59,90,96-98 establishcd that the 3-methyl-4-benzoyl... 

Three tautomeric structures (1,2-dihydro 27, 1,4-dihydro 28, and 3,4-dihydro 29) are possible for N-unsubstituted dihydroquinolines, which retain the aromatic benzene ring, and two structures 27 and 28 for N-substituted derivatives. No information on the tautomerism of such dihydroquinolines and stability of the possible tautomers was available when the earlier review (76AHCS1) was published. 

Fully unsaturated monocyclic 1,4-diazepines have been reported only recently. Representatives of the three tautomeric systems 1H-, 2H-, and 6//-l,4-diazepines are known, but 5//-l,4-di-azepines have not been described. 

In azo couplings with carbonyl compounds, three tautomeric products are possible, compared with only two for phenols and aromatic amines (discussed in Section 12.1). The ketohydrazone 12.75 is most often dominant, but for easily enolizable 1,3-dicarbonyl compounds (X=CO-R and similar structures) the azoenol 12.76 is the major product. The azoketone 12.77 is often postulated as primary product, but has rarely been identified in an unambiguous fashion using modern methods. The CH2 group should be easily detectable in the lH NMR spectrum. 

For the diazine 52 there are three tautomeric forms conceivable. When R = C02Et, 53, the situation is complicated by the possibility of an additional pathway for tautomerism. The IR results for this system are in fact ambiguous, and the investigators mention the possibility of cooperative intermolecular proton transfer being responsible for broad bands in the spectrum (111). 

A -Acylhydrazones of 1,3-dicarbonyl compounds can exist in three tautomeric forms enhydrazine 75A, hydrazone 75A, and 5-hydroxypyrazoline... 

Selected computed structural data on the three tautomeric forms of protonated NNtM, DNNtM and NDNtM are depicted in Figure 33. Only the most stable oxime isomers are presented. As long as only two functional groups are attached to the central methanide carbon, the entire molecule remains planar due to resonance stabilization, whereas introduction of a third group, either NO or NO2, results in rotation of at least one group, preferably the nitro group. Flowever, the CN3 moiety in the nonplanar species remains... 

The 1,2,5-oxadiazole ring is a stable system and annular-group tautomerism is not favored. Although three tautomeric forms can be drawn for 3-hydroxyfurazans (Scheme 3) IR and NMR data for chloroform solutions show only the presence of the hydroxy compound. Ring-chain tautomerism is an important feature of furoxan chemistry and the equilibration between the isomeric furoxans is discussed in detail later in this chapter (Section 4.05.5.2.1). 

Hydroxy-l,2,4-thiadiazoles can exist in three tautomeric forms (Scheme 5). Chemical evidence suggests that the OH form (8) predominates. However, UV data suggest that the lactam form (9) is the major tautomer in ethanol (84CHEC-I(6)463>. 

It is well known that l,3-thiazine-4,6-diones can exist in three tautomeric forms <1960CB671, 1976KGS1042>. Cycloaddition of chlorocarbonyl ketenes with thioamides has been reported to produce only the 4-hydroxy-l,3-thiazin-6-ones, whereas the same reaction with amides gives either 4-hydroxy-1,3-oxazin-6-ones or a mixture of tautomers depending on the substituents on the starting materials <2005ARK(xv)88>. 

From the second formula it is clear that three tautomeric structures are possible, according as both hydrogen atoms are ionisable (as in the formula), or one or both atoms are absorbed into the complex, being attached by co-valencies to either a sulphur or an oxygen atom. 

In the case of thiazine-4,6-diones, in contrast to the spectrum of the unsubstituted compound 92 (C=0,1640 cm ), there are three absorption bands. One is at 1640 cm-1, corresponding to the enol form, and two are at 1690 and 1730 cm"1, corresponding to the diketo form. In this example, the H-NMR spectrum suggests the presence of three tautomeric forms 93,94 and 95. In conclusion, we record a few absorptions bands for two thiazine-2-thiones (96) [82JCS(P1)2149]. 

The aromatic 3-substituted 1,2,3-triazole 1-oxides are represented by the formula 456 (Scheme 130). The parent compound 344 is one of the three tautomeric forms shown in Scheme 101. 

The parent 2-hydroxyselenophene possesses in principle three tautomeric forms (15, 16, 17) but the oxo form (17) predominates. In the 2-hydroxy-1-ben-zoselenophene (18) and l-hydroxy-2-benzoselenophene (20), where loss of heterocyclic ring resonance energy on tautomerism to 19 and 21 will be much less than for the non-annelated heterocycle, the latter oxo tautomers are preferred (Scheme 2) [26],... 

Presumably the NH-tetrazoles with no functional substituents on the endocyclic carbon can exist in three tautomeric forms, which are the 1H-, 2H-, and 5//-tautomcrs 24, 106, and 127, respectively (Equation 5). 

Azapurines are important compounds, if only because of the involvement of some of them in cancer chemotherapy. From the viewpoint of this review they present, moreover, the interesting possibility of another tautomeric form with the proton fixed at N-8 of the pentagonal ring. Very recent experimental isolation of the N-methylated derivatives of the three tautomeric forms, N(7)H,... 

The Gadamer system of three tautomeric components does not necessarily take for granted the simultaneous action of all three tautomeric equilibria, but rather it assumes two consecutive equilibria with the carbinolamine form (B) as an intermediate. 

A-2-Thiazoline-5-one may exist in three tautomeric forms (Scheme 108). The tautomeric equilibrium has been studied by H NMR (446. 453. 457. 464), infrared (453. 464-466). and ultraviolet (453, 464) spectroscopies 13C NMR data would be very instructive since model compounds for the three tautomers are now available. Polar solvents favor the enolic (211b) and the mesoionic (211c) forms (Table VII-12), the later being even more favored by high dilution (464). The percentage of the enol... 

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