3- hydroxy-, tautomers

Diethyl methyloxalacetate (106J, R = Me) adds to tetrahydropyridine and forms a new pyrroledione ring, but diethyl oxalacetate gives a product which is shown to be the enol form of the corresponding dione [2744]. The 1,2-double bond of 3A/-indoles undergoes a cycloaddition on treatment at ambient temperature with either diethyl oxalacetate or oxalopropionate. When R = H, the product may exist as its 2-hydroxy tautomer [3394]. Successive N- and... 

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). 

The O-alkyl derivatives of those A-oxides, which exist partly or entirely as (V-hydroxy tautomers, may be made by primary synthesis (as above) or by alkylation. Thus, 5,5-diethyl-1-hydroxybarbituric acid (936 R = H) with methyl iodide/sodium ethoxide gives the 1-methoxy derivative (936 R = Me) or with benzenesulfonyl chloride/ethoxide it gives the alkylated derivative (936 R = PhS02) (78AJC2517). 

AT-Oxidation is very sensitive to steric effects, since 1-substituted lumazines and pterins give only 5-oxides and the presence of bulky substituents at position 7 also directs oxidation to N-5. The pteridine 5-oxide (52) and 8-oxide (53) and the 5,8-dioxide (55) contain the AT-oxide groups as such, even when the possibility of AT-hydroxy tautomers exists, as in (53) i(54). 

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

The problem of tautomerism is simpler in the case of 1-substituted pyrazolin-3-ones since only two forms, the OH (140a) and the NH (140b), are possible. The OH form is the more stable and is the only one present in the crystal (Section 4.04.1.3.1). In protic solvents, like water or methanol, the equilibrium position is much more evenly balanced between the OH and NH forms. Finally, 4-hydroxypyrazoles (141) exist as such. A CNDO/2 calculation justifies the result that 4-hydroxy tautomers are relatively more stable than... 

No definite experiments have been carried out with regard to the relative stability of the tautomers of 2-substituted indazolones 111. On the basis of basicity arguments, (he hydroxy tautomer 111a was considered to be preferred [96JCS(P2)2263],... 

In the prototropic equilibrium, 3-hydroxybenzisoxazole exists exclusively as hydroxy tautomer 136a (Scheme 51) [76AHC(S1), p. 310]. 

A well-studied case of tautomerism is that of l,2-diazepin-4-ones tautomers 47a and 47b were characterized by NMR, the former being the most stable (85JOC2141). 3,5-Dihydro-4//-2,3-benzodiazepin-4-ones exist as 48a and not as 4-hydroxy tautomers 48b (74JHC401). 

Wentrup s paper [98JCS(P2)2247] contains one of the very few contributions to the tautomerism of functionalized 1,3-diazepines. l,3-Dihydro-l,3-diazepin-2-ones (49a) exist as such and not as hydroxy tautomers 49b ( H and NMR in DMSO solution and IR in the solid state). 

It is believed (54IZV47 72JPR353) that in the first stage the intermediate 282 is formed due to the addition of the CH acid to the enamine moiety with subsequent elimination of amine. The enol form of the intermediate 282 undergoes cyclization in two fashions, depending on the nature of substituent X. In the case of the ester (X = OMe) the attack is directed to the cyano group to form substituted 3-methoxycarbonyl-I//-pyridin-2-one (283) or its tautomer (2-hydroxy-3-methoxycarbonylpyridine). With the amide (X = NH2) intramolecular condensation leads to 3-cyano-l//-pyridin-2-one and its hydroxy tautomer (284). 

For most simple phenols this equilibrium lies well to the side of the phenol, since only on that side is there aromaticity. For phenol itself, there is no evidence for the existence of the keto form. However, the keto form becomes important and may predominate (1) where certain groups, such as a second OH group or an N=0 group, are present (2) in systems of fused aromatic rings and (3) in heterocyclic systems. In many heterocyclic compounds in the liquid phase or in solution, the keto form is more stable, although in the vapor phase the positions of many of these equilibria are reversed. For example, in the equilibrium between 4-pyridone (118) and 4-hydroxypyridine (119), 118 is the only form detectable in ethanolic solution, while 119 predominates in the vapor phase. " In other heterocycles, the hydroxy-form predominates. 2-Hydroxypyridone (120) and pyridone-2-thiol (122) are in equilibrium with their tautomers, 121 and 123, respectively. In both cases, the most stable form is the hydroxy tautomer, 120 and 122. ... 

The 3-OH substituent of the 3-hydroxy tautomer of the pyridazino[6,l-A]quinazoline 22 was exchanged for a Cl group on treatment with POCI3 and the chloro group was replaced on reaction with secondary and primary amines and with alkoxides <2000HC0147>. 

One representative of the oxazolo[4,5-/][ 1,6]naphthyridine system, viz. the ester 62, is produced in four steps by annulation of 2-(dicthy lam ino)oxazolo[4,5- pyridine (Scheme 20). Whether the final product exists mainly as the hydroxy tautomer or as the 9//-6-one cannot be deduced from the spectral data presented alkylation occurs either at the oxygen or at N-9, and gives either 63 or 64 <1993SC2931>. 

In contrast to the azaquinones 1 and 3, there is no literature report on the isomeric azaquinone 2. Reported hydroxy azaquinone 17 obtained by oxidation of 2,3,4-pyridinetriol can be considered to be its 2,3-dioxo-4-hydroxy tautomer (Scheme 5) (1883JPR257). In addition, this compound was identified only as its solvate with the alcohol of crystallization, which suggests the possibility of structure 18 instead [73AG(E)139]. 

Karelson et al. [268] used the AMI D02 method with a spherical cavity of 2.5 A, radius to study tautomeric equilibria in the 3-hydroxyisoxazole system (the keto tautomer 13 is referred to as an isoxazolone). AMI predicts 13 to be 0.06 kcal/mol lower in energy than 14 in the gas phase. However, the AMI dipole moments are 3.32 and 4.21 D for 13 and 14, respectively. Hydroxy tautomer 14 is better solvated within the D02 model, and is predicted to be 2.6 kcal/mol lower in energy than 13 in a continuum dielectric with e = 78.4. Karelson et al. note, however, that the relative increase in dipole moment upon solvation is larger for 13 than for 14 (aqueous AMI dipole moments of 5.05 and 5.39 D, respectively). This indicates that the relative magnitude of gas-phase dipole moments will not always be indicative of which tautomer will be better solvated within a DO solvation approach — the polarizability of the solutes must also be considered. In any case, the D02 model is consistent with the experimental observation [266] of only the hydroxy tautomer in aqueous solution. 

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