Tautomers compounds

The H NMR spectra of la-f and 3d-c, 3d-a, 3d-b, 3e-b, 3e-f proved that, in DMSO solution. Each set of compounds formed three-component ring-chain tautomeric mixtures, containing epimeric naphthoxazines together with the open-chain tautomer. Compounds displayed singlets at 8 5.40-6.32 due to NphCHArNH 8.41-8.73 due to NH = CHAr. 

Acylamino)benzamides give quinazolin-4(lff)-ones 7 in moderate yield on cyclization with phosphorus pentoxide. However, although reported as 1 //-tautomers, compounds 7 obviously exist as the corresponding 3//-tautomers (see p 9). 

Tautomers Compounds are structurally distinct, but are in rapid equilibrium. Usually, the... 

As a result of the observations discussed above, ethyldiazoacetate (EDAC) (30) has become a commonly used 1,3-dipole in the Pechmann pyrazole synthesis. In efforts toward the rational design of growth inhibitors of Mycobacterium tuberculosis, Kozikowski and co-workers used this strategy for the synthesis of 31. Treatment of a mixture of alkyne 29 and ED AC under microwave conditions resulted in the preparation of 31 as a mixture of 1 -H and 2-H tautomers. Compound 31 proved inactive in the anti-TB assay, thereby proving the importance of an isoxazole moiety for anti-TB activity, as previous work by these authors suggested. ... 

A second class of molecules with multiple representations are tautomers, compounds involved in an equilibrium of sin-gle/double bond shifts and hydrogen migration. Barbituric acid, 2,4,6-trihydroxypyrimidine, can be represented by the tautomeric forms (13), (14), (15), and (16) ... 

Of all the methods described for the synthesis of thiazole compounds, the most efficient involves the condensation of equimolar parts of thiourea (103) and a-haloketones or aldehydes to yield the corresponding 2-aminothiazoles (104a) or their 2-imino-A-4-thiazoline tautomers (104b) with no by-products (Method A, Scheme 46). 

The symmetrical disubstituted thioureas such as 137 do not give a thiazolic ring (Scheme 66), but give compounds of type 138 or 139, which are derived from the tautomer imino form of the 2-aminothiazole (86). 

Indole is a heteroaromatic compound consisting of a fused benzene and pyrrole ring, specifically ben2o[ ]pyrrole. The systematic name, IJT-indole (1) distinguishes it from the less stable tautomer 3JT-indole [271-26-1] (2). Iff-Indole [120-72-9] is also more stable than the isomeric ben2o[ ] pyrrole, which is called isoindole, (2H, (3) and IH (4)). A third isomer ben2o[i ]pyrrole is a stable compound called indoli2idine [274-40-8] (5). 

The compounds 2- (16) and 4-pyridone (38) undergo chlorination with phosphoms oxychloride however, 3-pyridinol (39) is not chlotinated similarly. The product from (38) is 4-chloropyridine [626-61-9]. The 2- (16) and 4-oxo (38) isomers behave like the keto form of the keto—enol tautomers, whereas the 3-oxo (39) isomer is largely phenolic-like, and fails to be chlotinated (38). 

Since polar solvents would be expected to stabilize polar forms, a retreat towards the hydroxy tautomer (71) would be predicted in solvents less polar than water, and in the vapour phase. This is borne out in practice at equilibrium both 2- and 4-hydroxypyridine (as well as the 3-hydroxy compound, which even in water exists as an approximate 1 1 mixture of OH and NH forms) exist as such, rather than as the pyridinones. However, the 2- and 4-quinolinones remain in the NH (keto) forms, even in the vapour phase. Hydrocarbon or other solvents of very low polarity would be expected to give results similar to those in the vapour phase, but intermolecular association by hydrogen bonding often leads to a considerably greater proportion of polar tautomers being present than would otherwise have been predicted (77ACR186, 78JOC177). 

IR spectroscopy has been particularly helpful in detecting the presence of keto tautomers of the hydroxy heterocycles discussed in Section 3.01.6. Some typical frequencies for such compounds are indicated in Figure 4. Here again the doublets observed for some of the carbonyl stretching frequencies have been ascribed to Fermi resonance. 

Potential C-hydroxy compounds usually exist as the 0x0 tautomers, unless the hydroxy tautomer is appreciably stabilized by electron withdrawing or chelating substituents. The... 

Annular tautomerism (e.g. 133 134) involves the movement of a proton between two annular nitrogen atoms. For unsubstituted imidazole (133 R = H) and pyrazole (135 R = H) the two tautomers are identical, but this does not apply to substituted derivatives. For triazoles and tetrazoles, even the unsubstituted parent compounds show two distinct tautomers. Flowever, interconversion occurs readily and such tautomers cannot be separated. Sometimes one tautomeric form predominates. Thus the mesomerism of the benzene ring is greater in (136) than in (137), and UV spectral comparisons show that benzotriazole exists predominantly as (136). 

Compounds of types (286) and (287) are in tautomeric equilibria with 4- or 5-hydroxyazoles. However, the non-aromatic form is sometimes by far the most stable. Thus oxazolinone derivatives of type (287) have been obtained as optically active forms they undergo racemization at measurable rates with nucleophiles (77AHC(21)175). Reactions of these derivatives are considered under the aromatic tautomer. 

Only three systems belong to this group pyrazole (3), l//-indazole (4) and 2//-indazole (isoindazole 5). The fused carbon atoms in indazoles are numbered 3a and 7a. When R = H, annular tautomerism (76AHC(Si)i) makes the 3- and 5-positions of pyrazoles equivalent and thus the name 3(5)-R-pyrazole means that the compound is a mixture of tautomers with the substituent R in position 3 and in position 5. The same applies to TV-unsubstituted indazoles however, the numbering is identical in both tautomers and thus 3-R-indazole means either (4) or (5) (R or R = H). Since the indazole tautomer is largely predominant (Section 4.04.1.5.1), indazoles are usually represented by the formula (4). 

Following the classification of Chapter 4.01, three classes will be considered, (a) Compounds isomeric with aromatic compounds (6), (7) and (8). The quaternary, non-aromatic salts (Scheme 7, Chapter 4.01) will be discussed only in connection with protonation studies which lead to the conclusion of their non-existence. The carbonyl derivatives (9), (10), (13) and (14) will also be included here because it is possible to write an aromatic tautomer for each one, (9 )-(14 ), even if it is energetically unfavoured, (b) Dihydro compounds. In this class not only pyrazolines (15), (16) and (17) but also pyrazolidinones (18) and pyrazolinediones like (1) are included, (c) Tetrahydro compounds. Besides the pyrazolidines (19), the pyrazolidinetriones (2) are included here. 

Hi) Pyrazole rings containing carbonyl groups In this subsection compounds with a pyrazole C—O bond will be discussed independently of their aromatic character. In solution the tautomers of pyrazolinones, e.g. (78a), (78b) and (78c), are easily identified by their IR spectra (Figure 18) (76AHC(Sl)l). 

A parallel exists between the results of protonation and alkylation of pyrazolones since there is an alkyl derivative for each tautomer. The main difference is that the percentage of the different tautomers is thermodynamically controlled whereas that of alkyl derivatives is kinetically controlled. One has to remember that the alkyl derivatives thus obtained are the fixed compounds used in tautomeric studies. 

Analogously, pyrazolyl-aluminate and -indate ligands have been prepared <75JCS(D)749) and their chelating properties evaluated with cobalt, nickel, copper and zinc. Gallyl derivatives of pyrazoles and indazoles have been extensively studied by Storr and Trotter e.g. 75CJC2944) who determined several X-ray structures of these compounds. These derivatives exist in the solid state as dimers, such as (212) and (288). A NMR study in acetone solution showed the existence of a slow equilibrium between the dimer (212) and two identical tautomers (289) and (290) (Section 4.04.1.5.1) (81JOM(215)157). 

The reaction is very common in pyrazolone chemistry. Since alkoxypyrazoles and tautomerizable pyrazolones undergo this reaction and 3-pyrazolin-5-ones, like antipyrine, do not, it is assumed that the reaction takes place at C-4 of the OH tautomer. Pyrazolone diazo coupling is an important industrial reaction since the resulting azo derivatives are used as dyestuffs. For instance, tartrazine (Section 4.04.4.1.3) has been prepared this way. 3,5-Pyrazolidinediones react with aryldiazonium salts resulting in the introduction of a 4-arylazo group. As has been described in Section 4.04.2.1.4(v), diazonium salts couple in the 3-position with indazole to give azo compounds. 

One of the best methods of synthesis of isothiazoles is by direct oxidation of y- iminothiols (169) or their tautomers. The reaction is capable of many ramifications and is represented by the general equation shown in Scheme 27. The substituents represent a wide range of groups. Thus, iminothioamides (169 R = NH2) are oxidized to give 3-alkyl-5-aminoisothiazoles (170 = NH2), amidines (169 R = NH2) produce 3-amino compounds,... 

Bis(3,4-diethyl-2-pyrrolylmethyl)-3,4-dietliyl-l//-pyrrole (2), prepared in situ from the di-t-butylester of the 5,5 -dicarboxylic acid (/), reacts with 4//-1,2,4-triazole-3,5-dialdehyde (3) in di-chloromethane in the presence of trifluoroacetic acid and 2,3-dichloro-5,6-dicyano-/)-benzoquino-ne as an oxidation reagent. Dark blue crystals are obtained after chromatographic purification. The dark violet chloroform solution fluoresces purple at 360 nm and gives the NMR experiments 39. Which compound and which tautomer of it has been formed ... 

Carbanions derived from carbonyl compoimds are often referred to as etiolates. This name is derived from the enol tautomer of carbonyl compounds. The resonance-stabilized enolate anion is the conjugate base of both the keto and enol forms of carbonyl... 

The study of the chemistry of carbonyl compounds has shown that they can act as carbon nucleophiles in the presence of acid catalysts as well as bases. The nucleophilic reactivity of carbonyl compounds in acidic solution is due to the presence of the enol tautomer. Enolization in acidic solution is catalyzed by O-protonation. Subsequent deprotonation at carbon gives the enol ... 

Although nitrosation of (l-dicarbonyl compounds becomes increasingly more facile upon successive replacement of the a alkyl groups with perfluoroalkyl groups because of the increased ionization of the perfluorinated enolate (equation 7), the stability of the nitrosodiketone tautomers decreases Thus, 1,1,1-trifluoro pentane-2,4-dione and 1,1,1,5,5,5-hexafluoropentane 2,4 dione mtrosate much faster than penta-2,4 dione but yield ketoximes, which decompose upon workup... 

Another series includes the cyc/o-metaphos-phimic acids, which are tautomers of the cyclO polyphospha/enc hydroxides (p. 541). Similarly, halogen atoms in PX3 or other P- X compounds can be successively replaced by the iscx lcctronic groups -NH . -NHR, -NR2, etc., and sometimes a pair of halogens can b>e replaced by - NH or -NR. These, in turn, can be used to prepare a large number of other derivatives as indicated schematically opposite for P(NMe2)3 ... 

Many heterocyclic compounds exist as mixtures of tautomers. For example, 2-hydroxypyridine exists in equilibrium with 2-pyridone. 

Protons bound to heteroatoms in heterocyclic compounds are likely to be very mobile in solution and, where two or more heteroatoms are present in a structure, different isomers (tautomers) may be in equilibrium. As a case in point, consider the nucleotide bases (indicates the point of attachment to the sugar-phosphate backbone). 

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