Stable tautomer

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). 

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

Anions derived from cyclic imides may, of course, be named by the foregoing principles, but it is often desirable to name them so as to emphasize their functional character. To do so, the -imide name is changed to -imidide . Such anions are obviously mesomeric, but for nomenclature purposes they are considered to be derived from the more stable tautomer, the imide form, as shown in (201). 

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. 

Pteridines which carry a hydroxyl group are appreciably acidic and react rapidly with, diazomethane to yield 0-methyl derivatives this, of course, means that the alternative NH form must be still more strongly acidic because the most stable tautomer is always the weakest acid. 

Generally the name of a compound should correspond to the most stable tautomer (76AHCS1, p. 5). This is often problematic when several tautomers have similar stabilities, but is a simple and reasonable rule whose violation could lead to naming phenol as cyclohexadienone. Different types of tautomerism use different types of nomenclature. For instance, in the case of annular tautomers both are named, e.g., 4(5)-methylimidazole, while for functional tautomerism, usually the name of an individual tautomer is used because to name all would be cumbersome. In the case of crystal structures, the name should reflect the tautomer actually found therefore, 3-nitropyrazole should be named as such (97JPOC637) and not as 3(5)-nitropyrazole. 

High barrier is the barrier from the most stable tautomer to the less stable one. Intramolecular proton transfer. 

This technique provides quantitative information about tautomeric equilibria in the gas phase. The results are often complementary to those obtained by mass spectrometry (Section VII,E). In principle, gas-phase proton affinities, as determined by ICR, should provide quantitative data on tautomeric equilibria. The problem is the need to correct the measured values for the model compounds, generally methyl derivatives, by the so-called N-, 0-, or S-methylation effect. Since the difference in stability between tautomers is generally not too large (otherwise determination of the most stable tautomer is trivial) and since the methylation effects are difficult to calculate, the result is that proton affinity measurements allow only semi-quantitative estimates of individual tautomer stabilities. This is a problem similar to but more severe than that encountered in the method using solution basicities (76AHCS1, p. 20). 

Likewise for 4-aminopyrazoles 46 and 5-aminopyrazoles 47 (Scheme 28), the most stable tautomer possesses either the amino structure 46a [76AHC(S1), pp. 425, 445 98H(49)157]-or 47a [76AHC(S1), pp. 420, 444 84CHEC-I(5)167 96CHEC-II(3)1], X-Ray structural analysis revealed that the parent 4-aminopyrazole exists in the solid state in two polymorphic forms of amino tautomer 46a these forms differ only by the conformation of the NH2 group [98H(49)157j. 

MO studies (AMI and AMI-SMI) on the tautomerism and protonation of 2-thiopurine have been reported [95THE(334)223]. Heats of formation and relative energies have been calculated for the nine tautomeric forms in the gas phase. Tire proton affinities were determined for the most stable tautomers 8a-8d. Tire pyrimidine ring in the thiones 8a and 8b has shown a greater proton affinity in comparison with the imidazole ring, or with the other tautomers. In solution, the thione tautomers are claimed to be more stabilized by solvent effects than the thiol forms, and the 3H,1H tautomer 8b is the most stable. So far, no additional experimental data or ab initio calculations have been reported to confirm these conclusions. 

The reaction of l-dialkylaminobut-l-en-3-ynes 100 with 1,2-diaminoethane (80°C, H" ", 2 h) leads to a mixture of 5-methyl-2,3-dihydro-l,4-diazepine tautomers (4) (the most stable tautomers are shown) (83ZOR1541). 

In aqueous solution 133d is more stable than 133c and 133f is more stable than 133e (Scheme 89). In both cases the 2-keto-4-thio 133a form is the most stable tautomer. Thiouracils 132-134 behave as moderate bases in the gas phase, 134 being the most basic one. 

The structures of pyrrolo[l,2-c]pyrimidine 139 and its N-protonated form 140 were obtained from MP2/6-31G calculations (Scheme 92) [99JOC7788]. Proton affinities computed at the same level reveal that N-protonation is slightly preferred over protonation at the C7 position. The most stable tautomers of 2-substituted 5-methyl-7-hydroxy-l,2,4-tiiazolo[l,5-a]pyrimidine 141 were... 

Systematic investigations have deary demonstrated that in the presence of metal ions the conjugated hexahydroporphyrin forms are thermodynamically favored by complexation whereas in the absence of metal ions the porphyrinogen form with isolated aromatic pyrrole rings is the thermodynamically stable tautomer. 

A,A-Diethylcarbamoyl)methylene]-l-methyl-3,4-dihydro-2( l/f)-quinoxalinethione 178-183, IR, MS (stable tautomer) 65... 

DFT results suggested that the delocalized QMs 2a-4a (Scheme 2.10) and their related E isomers (2b-4b) are by far the most stable tautomers in the series.19 The structures that come next, the less delocalized /)-QMs 2c-4c in vacuum, and the quinones 2d-4d (Qs) are less stable by several kcal per mole in aqueous solution. 

These DFT data provide a consistent picture for the tautomerization equilibria involving the dimers 2-4, which highlight the extended quinone methides 2a, 3a, and 4a as the most stable tautomers for all biindolyl quinones investigated. 

For neutral guanine two stable tautomers are based on the keto form, labeled guanine I in Figure 5. The remaining three stable structures are based on the hydroxy form, guanine II. In the gas phase, guanine is found in a mixture dominated by the keto forms. In solution, the relative stability of the... 

Parchment et al. [271] have provided more recent calculations on the 3-hydroxypyrazole equilibrium at the ab initio level. They noted that tautomer 9, which was not considered by Karelson et al. [268], is the lowest-energy tautomer in the gas phase at levels of theory (including AMI) up to MP4/6-31G //HF/3-21G [271], Although 8 is the dominant tautomer observed experimentally in aqueous solution, in the gas phase 8 is predicted to be nearly 9 kcal/mol less stable than 9 at the MP4 level [271], Using a DO model with an unphysically small cavity radius of 2.5 A, Parchment et al. [271] were able to reproduce at the ab initio level the AMI-DO prediction of Karelson et al. [268], namely that 8 is the most stable tautomer in aqueous solution. With this cavity, though, 8 is predicted to be better solvated than 9 by -22.2 kcal/mol [271], This result is inconsistent with molecular dynamics simulations with explicit aqueous solvation [271], and with PCM and SCME calculations with more reasonable cavities [271] these predict that 8 is only about 3 kcal/mol better solvated than 9. In summary, the most complete models used by Parchment et al. do not lead to agreement with experiment... 

Physicochemical properties rather than reactivities were also explored. Molecular electrostatic potential (MEP) was calculated for the [l,2,4]triazolo[4,3- ]pyridine fragment 23, according to the CHELPG algorithm. This afforded a prediction of its H-bond acceptor ability in view of the synthesis of p38 MAP kinase inhibitors <2005JME5728>. Tautomerism was also examined for compound 24, also postulated as two possible acyclic structures. The ab initio self-consistent field (SCF)-calculated energies support 24a as the most stable tautomer <1999MRC493>. 

Enol esters are distinct from other esters not because of a particular stability or lability toward hydrolases, but due to their hydrolysis releasing a ghost alcohol (an enol), which may immediately tautomerize to the corresponding aldehyde or ketone. A well-studied example is that of vinyl acetate (CH3-C0-0-CH=CH2), a xenobiotic of great industrial importance that, upon hydrolysis, liberates acetic acid (CH3-CO-OH) and acetaldehyde (CH3-CHO), the stable tautomer of vinyl alcohol [25], The results of two studies are compiled in Table 7.1, and demonstrate that vinyl acetate is a very good substrate of carboxylesterase (EC 3.1.1.1) but not of acetylcholinesterase (EC 3.1.1.7) or cholinesterase (EC 3.1.1.8). The presence of carboxylesterase in rat plasma but not in human plasma explains the difference between these two preparations, although the different experimental conditions in the two studies make further interpretation difficult. 

In those cases where tautomeric structures are possible, the exclusive or predominant tautomer will be shown (Fig. 6.1). Thus, 1 is predicted to be the most stable tautomer in the gas phase and in solution. It is the only tautomer observed experimentally in solution and will be used to represent 4(5//)-oxazo-lones. The tautomeric mesoionic anhydro-4-hydroxyoxazolium hydroxide lb has not been observed spectroscopically but has been trapped in cycloaddition reactions.The amino tautomer 2 has been shown to be the exclusive and/or... 

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