Tautomers form proportions

Hydroxya2o dyes vary in the proportion of tautomers present from pure a2o tautomer to mixtures of a2o and hydra2one tautomers, to pure hydra2one tautomer. Almost all a2ophenol dyes (11) exist totally in the a2o form, except for a few special cases (9). 

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). 

Identification of the product(s) resulting from the reaction of heterocyclic compounds with diazomethane has been used in attempts to elucidate their tautomeric composition (for summaries, see references 7 and 41). This work was based on the assumption that if a compound which is capable of existing in both an —NH and an —OH form produced only the =NMe derivative when it w as treated with diazomethane, it existed entirely in the =NH form. On the other hand, formation of the —OMe derivative was interpreted to mean that a finite amount of the compound existed in the —OH form. In some cases the tautomer present in the solid state w as concluded to be different from that present in solution for example, 41 42 gave a higher proportion of the 3,4-dimethoxy derivative when ethereal diaz-... 

Trihydroxypteridine exists predominantly in the dioxo-mono-hydroxy form 191(R = H), its ultraviolet spectrum closely resembling those of both the 1- and the 3-methyl derivatives and that of l,3-dimethyl-7-methoxypteridine-2,4-dione (191, R = Me). These spectra are quite different from those of 8-methyl- (192, R = H) and l,3,8-trimethyl-pteridine-2,4,7-trione (192, R = Me), which are similar to each other and to those of other 8-substituted pteridine-2,4,7-triones. However, the ultraviolet spectrum of 2,4,7-trihydroxypteri-dine does, indeed, show that a small proportion of the trioxo form is present at equilibrium. A somewhat larger proportion of the 6-methyl derivative exists in the trioxo form, although structure 193 predominates. The trioxo form (194) of 2,4,7 trihydroxy-l,3,6-trimethyl-pteridine is the most important tautomer, but the corresponding 6-carboxylic acid exists entirely in the monohydroxy-dioxo form 195. 

The electronic effect of the substituent X on the 2-phenyl ring proved to influence the ring-chain tautomeric equilibria of 2-aryl-l-hydroxy-l,4-dihydro-2//-3,l-benzoxazines 79. While the proportion of the cyclic tautomer B in CDCI3 was 90% for the unsubstituted (X = H) and 70% for the />-methoxy derivative (X = OMe), no cyclic form could be detected in the case of the -dimethylamino compound (X = NMc2). Independently of the substituent X, the tautomeric equilibria of the regioisomeric 2-aryl-3-hydroxy-3,4-dihydro-2//-l,3-benzoxazines likewise contained no detectable amounts of the cyclic forms <1997CJC1830, 1998CJC389>. 

Thus, while the 3-hydroxyisoquinoline-3-isoquinolinone equilibrium (80 81) and that of the cinnoline derivatives (82 83) favour the keto forms (81, 83), the proportion of hydroxy tautomers is considerably greater than in the corresponding unfused systems. The benzo-fusion in 2- and 4-quinolinone and in 1-isoquinolinone has the effect of reducing the aromaticity of the heterocyclic ring, and consequently of lowering the proportion of the hydroxy tautomers. 

The acyclic, enolic compounds 7 and 9 may exist in either cis or trans forms. Methyl ethers of 7 have been isolated in the cis form,8 but it is not known whether the trans forms, which must be acyclic, exist. The relative proportion of isomers is controlled by the geometry of the parent sugar enediol. Although the acyclic forms are readily interconvertible tautomers, it appears that, in acidic medium, further reaction occurs much more rapidly than any equilibrating reactions. Compound 7 undergoes rapid elimination of a second hydroxyl group to give 11. This acyclic product, also, may exist as either a cis or a trans isomer, both forms of which have been isolated.8 The loss of a third molecule of water per molecule occurs after, or simultaneously with, the cyclization of 11 (see Section II, 3 p. 171), and results in formation of 5-(hydroxymethyl)-2-furaldehyde (5). 

During the dehydration of pentoses in acidic solution, the cis and trans 2-enes (homologs of 44 and 46 see p. 177) react rapidly to form the 3-enes, 94a and 94b. Anet8 has presented evidence for the existence of cis and trans forms of the 6-carbon 2-enes. The relative proportion of the geometrical isomers 94a and 94b is controlled by the ratio of the cis and trans forms of the reacting 2-enes and by the rate of interconversion through the tautomer, 72. The trans form (94a) is unable to cyclize, whereas the cis isomer (94b) could readily cyclize to 28 and this could be dehydrated to 2-furaldehyde (27). Formed by extended enolization of 94, the diene 72 has the electronic arrangement needed for cyclization to afford 75a, a tautomer of re-... 

NMR spectral evidence for the presence of the valence tautomeric thianorcaradiene (benzene episulfide) form (analogous to the arene oxide tautomer of an oxepin) has yet to be observed. The latter negative evidence, however, does not exclude the possibility of a rapid thiepin-thianorcaradiene equilibration since the number of monocyclic thiepins which have to date been synthesized is very small, and since the examples examined by NMR probably owe their stability to the very low proportion of benzene episulfide tautomer present. 

Although iV-hydroxypyrroles possess in principle several tautomeric forms, e.g. (76), (77) and (78), only the A-hydroxy form (76) has been observed for l-hydroxy-2-cyanopyrrole (73JOC173). In the case of 1-hydroxyindoles, where the potential loss of aromatic resonance energy will be much less, both tautomers (79) and (80) coexist in solution with the relative proportions being dependent on the solvent... 

Nonaqueous Lactam-amine (2) spectroscopy, p X measurements IR, UV spectroscopy more stable than tautomer 6, alkylaminocyto-sines exist in form 2 Change of the proportions of... 

Importantly, TV-carbamoyl derivatives of primary amines obtained from photolabile benzoins exist in varying proportions as cyclic hydroxyoxazolidinone tautomers. Therefore, the preparation of TV-carbamoyl derivatives of benzoins is applicable only for secondary amines and TV-alkylated amino acids. 244 At basic pH unsymmetrical benzoins, such as 3,5-dimethoxybenzoin, their mixed carbonate and carbamate derivatives, tend to equilibrate to the isomeric forms. Nevertheless, in TFA and aqueous solutions at pH 8 the structural integrity is fully maintained. 244 Preparation of 3,5-dimethoxybenzoin-derived carbamates of secondary amines and amino acids can be mediated by either CDI/methyl triflate in ni-tromethane 246 or 4-nitrophenyl chloroformate/DMAP in dry THF. 244 ... 

The solvent, temperature, and substituent (R and R1) -dependent ring-chain tautomerism of 2-pyridylaminomethylenemalononitriles (167 168) was studied (86JOC2988). 2-Pyridylaminomethylenemalo-nonitriles were prepared in the reaction of 2-aminopyridines and 2-(l-ethoxyalkylidene)malononitrile in ethanol at room temperature or in a melt at 120°C, and in a one-pot reaction, starting from 2-aminopyridines, a triethyl orthoester, and malononitrile at 110°C for 10 minutes. The content of the equilibrium mixture of 2-pyridylaminomethylenemalononitrile 167 (R = R1 = H) is shown in Table X. Elevation of the temperature increased the proportion of the chain tautomer. The ratio between the two tautomeric forms 167 and 168 is influenced primarily by the steric properties of substituents R and R1 in positions 6(6) and 3(9), respectively,... 

The ratio of 33A and 33B proved to be slightly solvent-dependent (Table V). The reactions of 3-amino-l,2-propanediol with substituted aromatic aldehydes in CDC13 resulted in five-component ring-chain tautomeric equilibria. Besides the open-chain form 34A, two epimeric oxazolidines (34B and 34B ) and two epimeric tetrahydro-l,3-oxazines (34C and 34C ) were identified in the tautomeric mixture. The proportions of the tautomers in the equilibrium for X = p-NC)2 were [34A] [34B] [34B ] [34C] [34C ] = 40.7 7.0 5.9 9.7 36.7 (94MI1, 94MI2). 

In complete agreement with the deductions from infrared data, the calculations estimate the tautomers 37, 40, and 43 as the most stable forms of 2-hydroxypurine, 6-hydroxypurine, and 8-hydroxypurine, respectively, followed very closely, however, by tautomers 34 and 39 for the first two isomers. Their existence as mixtures of tautomeric forms in comparable proportions seems therefore highly probable. On a relative scale the most stable of the three isomers should be the 8-hydroxy one (certainly because of the high content of its 77-electronic delocalization), which should, in fact, be appreciably more stable than the 2- or 6-isomers, which are predicted to be of comparable stability. 

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