Reversal in tautomeric form

Causes of Reversal in Tautomeric Form Aromatic Resonance 3... 

The reaction of thioethers with ethyleneimine in the presence of acid yields sulfonium compounds. The reaction is reversible under alkaline conditions (125). Compounds in which double-bonded sulfur can exist in tautomerism with a form having a free SH group, such as thiourea (126,127), thiocarboxyhc acids (128), and thiophosphates (129), react to give aminoaLkylated products. The P-aminoethyl thiocarboxylate rearranges to give the amide. 

Also, (5-phenyl-l,3,4-oxadiazol-2-yl)-7-hydroxycoumarin is a tautomeric compound. In dilute solutions it is almost totally present in its protonated nitrogen tautomeric form. The deprotonation is a reversible process (Scheme 2). Quantum-mechanical calculations were carried out and correlated with experimental observations <2000SAA1773>. 

The NMR chemical shifts of the C=N carbon in the open tautomeric forms of 2-aryl-substituted 3,4-dihydro-277-1,3-benzoxazines 5 and l,4-dihydro-277-3,l-benzoxazines 6 exhibited a reverse dependence on the benzylidenic substituents X. Electron-withdrawing substituents caused shielding (the shift was reduced), while electron-donating ones caused deshielding <2003JOC2151>. 

The facility of 1H-azepines to form transition metal carbonyl complexes was realized soon after they were first synthesized. Variable temperature HNMR studies on the tricarbonyliron complex formed either by photolysis of 1-ethoxycarbonyl-l//-azepine with tricarbonyliron in THF, or by heating the azepine with nonacarbonyldiiron in hexane, demonstrated that it undergoes rapid reversible valence tautomerism and that there is considerable restricted rotation about the N—CO bond (B-69MI51600). The molecular geometry of the complex has been determined by X-ray analysis (see Section 5.16.2.2). 

For the particular case of 2- and 4-mercaptopyridines and 2-mercaptopyrimidines and by means of absorption UV-VIS spectroscopy, Stoyanov and collaborators122 have shown that polar solvents shift the thiol/thione tautomerism towards the thione form, while in dilute solutions of nonpolar solvents the thiol form predominates. However, one of the most significant contributions of this work122 is the observation of self-association. It also favors the thione forms and is followed by quantitative transformation of the thiol form into the corresponding symmetrical disulfides (see Scheme 6). More importantly thione-disulfide process is reversible in water, which can be of some relevance in biological systems. 

Similarly, the reversal of the thermochemical stability order upon one-electron oxidation has been demonstrated theoretically and experimentally for several heteroatom substituted carbonyl/enol pairs, e.g. esters [52,53] and acids [54,55]. A recent detailed evaluation of the substituent effect by Heinrich, Frenking and Schwarz using ab initio molecular orbital calculations [56] is summarized in Table 3. Both a- and 7t-donors X stabilize the two cationic tautomeric forms, but with Ji-donating groups (X F, OH, NHj) the enol radical cations are much more stable than the corresponding keto ions. On the other hand, with c-donor/rt-withdrawing substituents this thermochemical preference is less pronounced and in the case X BeH the order of relative stabilities of ionic keto/enol pairs is even reverted. 

When triethyl l,3,5-triazine-2,4,6-tricarboxylate is treated with acetimidamide hydrochloride7 or propionimidamide hydrochloride8,9 in dimethylformamide at 90-100°C the corresponding pyrimidines are formed in 80-85% yield. The reaction proceeds by reversible in-situ tautomerism of the amidine hydrochloride to the alkene-1,1-diamine and its participation in a [4 + 2] cycloaddition with the triazine. The cycloaddition is followed by a retro Diels-Alder reaction with loss of ammonia and ethyl cyanoformate. The thermal conditions (>80°C) required for effecting the retro-Diels-Alder reaction and the deliberate use of the amidine hydrochlorides facilitates the amidine tautomerism and seems to be essential for aromatization of the initially formed cycloadduct.7-9... 

Two groups have applied a reverse procedure and estimated quantitatively the difference in empirical resonance energy between two tautomeric forms by comparing the equilibrium of the heteroaromatic with that of a model for the hypothetical localized system. Scheme 2 illustrates the relationship for the pyridone system. 

Woodward and Evans [14, 17, 18] advanced solutions to this matter during the course of their studies. The second difficulty stemmed from the rapid equilibrium between the two tautomeric forms, 2a and 2b, of colchiceine (10-demethyl-colchicine), the free tropolone that is the final intermediate in all pre-1992 syntheses (Scheme 1). As a result of this equilibrium, O-methylation of colchiceine affords a ca. 1 1 mixture of colchicine and isocolchicine (3), the latter product differing from 1 in that the positions of the methoxy and carbonyl moieties (as well as the associated double-bonds) in ring-C are reversed. 

By breaking one bond in the phosphorus anion, for example, 1-2, 2-6 or 1-6 and forming 3-7, 3-5 or 5-7, the P atoms in the three-membered ring are successively interchanged with the three bridge P atoms (3.50). Each of the seven P atoms can end up in any of the possible positions by appropriate rearrangements, leading to 7/3 = 1680 identical valence tautomeric forms. At room temperature this reversible dynamic process is rapid compared to the NMR time scale (Chapter 13). 

Modulation of the pull-push conjugated n-electron system in cyanine dyes is demonstrated as an efficient approach to tuning the fluorescent emission profile. Speeifleally, the removable trigger moiety on the backbone of the polymethine n-eleetron system was implemented for the design of ratiomet-ric eyanine-based sensors. As illustrated in Figure 5.6, hydroxycyanine CyAE displayed remarkable blue shifts in absorption (-175 nm) and emission spectra (-115 nm) with reversible tautomeric forms of CyAE and CyAK or CyAD. 

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