Tautomeric shift

This equilibrium is followed by a rate-determining tautomeric shift (18 — 16 electrons) to give a coordinated alkyl group ... 

The aromaticity of the pyrimidine and purine ring systems and the electron-rich nature of their —OH and —NHg substituents endow them with the capacity to undergo keto-enol tautomeric shifts. That is, pyrimidines and purines exist as tautomeric pairs, as shown in Figure 11.6 for uracil. The keto tautomer is called a lactam, whereas the enol form is a lactim. The lactam form vastly predominates at neutral pH. In other words, pA) values for ring nitrogen atoms 1 and 3 in uracil are greater than 8 (the pAl, value for N-3 is 9.5) (Table 11.1). 

The Knoevenagel reaction between o-hydroxyaryl aldehydes and ketones and substituted acetonitriles affords high yields of 3-substituted coumarins in aqueous alkaline media <96H(43)1257>, whilst 4-hydroxycoumarins have been elaborated to pyrano [3,2-c]benzopyran-5-ones by reaction with aromatic aldehydes and malononitiile <96P148>. The imine (10) resulting from the complex reaction of o-hydroxyacetophenone with malononitrile undergoes a 1,5-tautomeric shift in solution <96JCS(P1)1067>. 

Exchange of the 5-H of uridine (72, Ri = H, Rg = OH, R3 = H, X = 0) in slightly basic D2O at 60° using 2-mercaptoethylamine as base has been reported. Similar exchange was also observed in deoxyuridine (72, Ri=R2 = Rs = H, X = 0) and uridine monophosphate (72, Ri = H, R2 = OH, R3 = PO3H2, X = 0), and a probable mechanism involves a Michael 1,4-addition across the double bond followed by a tautomeric shift and then elimination of the C-5 hydrogen and the nucleophile. Exchange of the 6-H or uridine in the presence of ammonium sulfite at 37° proceeds best at pH 9. The mechanism involves deprotonation of the bisulfite-uridine complex by the ammonia or added amines. ... 

Steady-state and time-resolved emission spectroscopy was used to study the interaction of E. colt PNP with its specific inhibitors formycin B, FA, and A -l-methylformycin A. Complexation was found to induce tautomeric shifts <2000BBA1467>. Carbocyclic analogues of formycin A and B have been recently synthesized <2004T8233>. The synthesis utilized 417 as starting material which was converted into 418 via a multistage synthesis. The latter could be converted into the formycin analogue (Scheme 36) <2004TL8233>. 

It may well be, as Buckingham points out [104], that, at room temperature, under neutral conditions, and for a limited number of structural types, such as phenylhydrazones, no tautomeric shift to azo compounds takes place. The experimental facts are, however, that, under forcing conditions, aliphatic hydrazones have indeed been converted into azo compounds although often only in modest yield. 

Members of the tetracyclic dibenzopyrrocoline alkaloid family can be prepared by the intramolecular ring closure of l-(o-halobcnzyl)-tetrahydroisoquinoline derivatives. (3.38.)47 The analogous transformation of dihydroisoquinolines (3.39.) proceeds probably through the isomeric enamine form obtained by the tautomeric shift of the double bond 48 The palladium-carbene catalyst system applied in these reactions was also effective in the preparation of indoline, indolizidine and pyrrolizidine derivatives 49... 

Before the polymerase moves on, the cytosine undergoes a tautomeric shift from C to C. The new nucleotide is now mispaired. 

The lactone 223 was isolated from 2-benzoyl-3-hydroxymethylquin-oxaline 1-oxide 221 on treatment with alkali and subsequent acidification, probably by intramolecular Cannizzaro reaction of 2-benzoyl-3-quinoxaline carboxyaldehyde (222), which in turn is obtained from 221 by a series of tautomeric shifts and 1,4-elimination.221... 

One additional aspect of complexity in defining the molecular structure of polyisocyanides arises, especially wherein the substituent R group is aralkyl and contains hydrogen on the benzylic a-carbon atom, as in poly(a-phenylethyl isocyanide). The possibility of tautomeric shift of the hydrogen atom on the a-carbon is reasonably likely (5), whereby the 7t-electrons of the original... 

Experimental evidence122 shows that 5-azacytosine and 5-azacytidine exist in the lactam-amine form, type 13. Unfortunately, the tautomeric properties of 3-methyl-5-azacytosine have not been studies, so it is difficult to decide whether 5-aza-substitution in 3-methylcytosine causes a tautomeric shift toward the imine form. 

The tautomeric studies of azacytosines are not so complete as those of cytosine itself. The contribution of other tautomeric forms of azacytosines to the tautomeric equilibrium has not been evaluated (because of lack of model tautomeric compounds). It appears that 6-aza-substi-tution causes a tautomeric shift from form 3 of cytosine toward its imine form, 6. Thus, upon 6-aza-substitution the contribution of the imine tautomers to the tautomeric equilibrium of cytosine increases, while that of tautomers 3 decreases. 

Substitution of a Hydroxy, Methoxy, or Amino Radical at the Amino Group of Cytosine Tautomeric Shift 2 — 6... 

Table VII contains the results of the CNDO/2 calculation158 on the energy of cytosine tautomers 2, 3 or 6 and of some derivatives. It can be seen that the calculated energy shifts are in agreement with the effect of substitution on the tautomeric equilibrium of cytosine discussed in Section II, B. Thus, a 5-fluoro substituent causes a small tautomeric shift toward forms 3 (dB i3F Cyt - di ,3t = 2.98 kcal/mole) or 6 (JB l8F Cyt — = 4.87 kcal/mole), while a 6-fluoro substituent...

Predicted tautomeric shifts also correlate satisfactorily with the experimental shifts observed in the cytosine, 2 T4-amino- and N -hydroxycytosine series. In accordance with the experimental evidence, the calculations predict a significant tautomeric shift toward imine form 6 upon amino or hydroxy substitution at the amino group of cytosine. Previously reported calculations3 also gave a satisfactory interpretation of the tautomeric shift caused by hydration of cytosine. 

Electron flow could induce long-range tautomeric shifts and initiate nucleophilic attack at peptidyltransferase or GTPase site... 

Examples of a tautomeric shift toward the imine form are relatively scarce among conjugated heterocycles. In our laboratory such calculations have been carried out, always by the CNDO/2 method, for two other cases, which seem worthwhile mentioning. 

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