Tautomerism in pyrimidines

Several papers have appeared on tautomerism in pyrimidines, including the parent molecule, pyrimidyl-2- and -4-cyanoacetic esters, and AT-substituted 4-aminopyrazolo[3,4-< ]pyrimidines. The last-mentioned system (5) is in equilibrium with (6) in aqueous solution. Interconversion is catalysed by acid and base, and proceeds via either an intermediate cation that is common to both neutral tautomers or through the anion. Other studies of condensed systems include... 

No data on tautomerism of dihydropyiimidines were available at the time of the early summary (76AHCS1), but much has been done since then. The results of tautomeric studies carried out during the period between 1976 and 1984 were reviewed comprehensively in [85AHC(38)l,pp. 63-77]. Later, Weis and vanderPlas published an excellent review on the synthesis, structure, and tautomerism of dihydropyrimidines [86H(24)1433], where the tautomeric interconversions of these compounds were discussed in detail. In a more recent review on dihydropyrimidines (94MI1), the question of tautomerism in partially hydrogenated pyrimidines was also included. 

Hydroxy, thiol, and amino groups in pyrimidine exist in tautomeric equilibria with their oxo, thioxo, and imino forms. An amino group in an electrophilic position exists predominantly as such, and the compound is named as an amine. Pyrimidines with a hydroxy or thiol group in an electrophilic position are dominated by the oxo or thioxo forms and are named as such, or with -one or -thione suffixes, if these are the principal groups. In the benzenoid 5-position, these derivatives are mainly present in the hydroxy, thiol, or amino forms and are named as such. Similar considerations apply to the nomenclature of quinazolines and perimidines <1996CHEC-II(6)93>. 

The ultraviolet absorption spectra of l,2,4-triazolo[4,3-a]pyrimidines have been studied. Amide-imidic add tautomerism in l,2,4-triazolo[4,3-ajpyrimidinones has also been studied using this tool [59JOC779 77HC(30)179], The spectra of the 5-oxo-l,2,4-triazolo[4,3-a]pyrimidines (158) exhibited three absorption bands at -230,260, and 310 nm (87T2497). The 7-oxo congeners (18), in contrast, revealed only one band at 230 nm (87T2497). 

The present volume encompasses a wide range of heterocyclic chemistry. Syntheses of heterocycles from thioureas are reviewed by T. S. Criffin, T. S. Woods, and 1). L. Klayman, while S. W. Schneller describes the chemistry of benzothiins and their derivatives (thiochromans, thiochromones, and thio-chromanones). Developments in chrom-3-ene chemistry are reviewed by L. Merlini. F. D. Popp contributes a chapter on the isatins. A discussion of theoretical aspects of the tautomerism of pyrimidines, by J. S. Kwiatkowski and B. Pullman, follows up a corresponding earlier contribution (Vol. 13) on tautomeric purines. In the final chapter P. and D. Cagniant describe the natural occurrence and synthesis of the benzofurans. 

The tautomerism of pyrimidines was discussed in Chapter 2, Section A,6. The tautomeric forms shown in Fig. 5-1 predominate. However, it is possible that minor tautomers such as the following are sometimes preferentially bound into active sites of enzymes where the dielectric... 

The UV spectra of 9-(phenylamino)tetrahydro-4f/-pyrido[ 1,2-a] pyrimidin-4-ones 23 indicated the presence of an imine-enamine type of tautomerism in solution. A carboxyl or ester group in position 3 (R1 = COOR3 R3 = H, Et) and a methyl group in position 6 (R = Me) shifted the equilibrium toward the enamine form in a polar solvent [85JCS(P1) 1015]. For the imine tautomer, UV maxima at 235-250 nm and 280-300 nm and for the enamine absorbances at 260-265 nm and 355— 365 nm are characteristic. 

Irreversible lactim-lactam tautomerization was recognized a long time ago and is generally achieved by either heat or catalysts. One of the synthetic applications was reported by Knorr as early as 1897. Later, this reaction was first applied to the synthesis of pyrimidine nucleoside by Johnson and Hilbert, thus being called the Hilbert-Johnson reaction (HJR). The reaction has been employed as one of protocols for the preparation of pyrimidine nucleosides. The biological and medicinal interest in pyrimidine affords further impetus to prepare new types of derivatives. Because of the synthetic utility of the HJR for synthesis of pyrimidine nucleosides, a more sophisticated version of the HJR has been developed by Vorbriiggen (the silyl HJR VHJR) employ-... 

The first of these questions has, of course, to be considered, in a broader way, for the probability of tautomerism in both the purines and the pyrimidines. In this respect, the general theoretical prediction, made by us on the basis of simpler calculations as early as 1962178 and confirmed later by other authors (e.g., Danilov179) and by the present refined calculations, is that it is the guanine and cytosine constituents of the nucleic acids which should have the greatest tendency to exist in their respective (lactim and imine) rare forms. These are therefore the bases which should have the greatest probability of being involved in spontaneous mutations insofar as tauto-merization may be considered as a cause of such mutations. The transformation G-C -> A-T should thus be more frequent than the reverse one. 

Studies of tautomerism, in which the spectra of aminopurines and their substituted-amino analogs were compared, show clearly that the amino and not the imino form predominates.8 Confirmation has been supplied by infrared13 and by nuclear magnetic resonance studies on adenosine and guanosine.14,15 Alkylation of the pyrimidine ring nitro-... 

Stolarski R, Remin M, Shugar D (1977) Studies on prototropic tautomerism in neutral and monoanionic forms of pyrimidines by nuclear magnetic resonance spectroscopy. Z Naturforsch C 32 894—900... 

The parent compound, perhydropyrrolo[l,2-a]pyrimidine (428), is obtained by the reaction between 4-chlorobutanal and 1,3-diaminopropane in the presence of potassium carbinate (83TLI559). A study of ring-chain tautomerism in such systems shows that in neutral aqueous solutions 428 predominates [84ACS(B)526]. 6-Propyl and 6-heptyl derivatives (430) were prepared by reduction of429 with LiAIH4. Hydroxyethylation of 430 with 50% excess ethylene oxide gives rise to 431 (76URP527433). 

Table 10. Investigation of lactam-lactim and thione thiole tautomerism in the pyrimidine rings of inosine and 9-(p-D-ribo-furanosyl)purine-6-thione from C-6 chemical-shift data ...

With different substituents in the /f-dicarbonyl compounds, the substitution pattern of the products is compatible with the 6-amino nitrogen condensing with the carbonyl group which is least tautomerized in the enol form. The orientation in condensations with ix,/l-unsaturated carbonyl compounds results from the addition of C5 of the pyrimidin-6-amine to the Michael system.254... 

The keto-enol and thione-thiol tautomerisms in pyridine and pyrimidine derivatives were already discussed in Chapter 6. Azo-hydrazo tautomerisril, CH—N=N C=N—NH, has been studied by Burawoy and co-workers34. Another type of tautomerism has been identified in the case of carbohydrates. The proportions of the ring and open structures of carbohydrates have been determined by measuring the intensity of the 280 mp carbonyl band. Pacsu and Hiller have shown that D-glucose exists almost completely in the ring form in neutral solution and to the extent of 0T per cent in the open chain form in acid solution. 

XXV. A Basic Set of Parameters for the Investigation of Tautomerism in Purines Established from Carbon-13 Magnetic Resonance Studies Using Certain Purines and Pyrrolo[2,3-d] -pyrimidines. 

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