4 -Pyrimidone

Flucytosine. Flucytosine (17) or 5-fluorocytosine (4-amino-5-fluoro-2-pyrimidone, 5-FC), C H FN O, is a pyrimidine derivative, that is efficient against Candida albicans Cryptococcus neoformans and Torulopsis glabrata. 

Repeat your analysis for tautomeric equilibria between 4-hydroxypyridine and 4-pyridone, 2-hydroxypyrimidine and 2-pyrimidone and 4-hydroxypyrimidine and 4-pyrimidone. For each, identify the favored (lower-energy) tautomer, and then use equation (1) to calculate the ratio of tautomers present at equilibrium. Point out any major differences among the four systems and rationalize what you observe. (Hint Compare dipole moments and electrostatic potential maps of the two pyridones and the two pyrimidones. How are these related to molecular stability )... 

Dichloro-2-pyrimidone reacts readily with thiourea. ... 

The ethoxycarbonyl derivative 11 is converted into derivatives 12 of 2-pyrimidone by the action of primary aliphatic amines.291 The products 12cyclize to the 5-aminopyrimido[4,5-/>][l,5]ben-zodiazepinones 13 on heating with ethanolic triethylamine.292... 

A. Mononucleotides.—A new journal has appeared in the past year consisting of abstracts of papers published in the nucleotide and nucleic acid fields. The use of nucleosides and nucleotides as potential therapeutic agents has been reviewed. Nucleotides which have been prepared recently using conventional methods of phosphorylation include those derived from 6-methylthiopurine ribonucleoside (la), 5-methylsulphonyluridine (lb), l-(jS-D-ribofuranosyl)-2-pyrimidone (Ic), 3-(jS-D-ribofuranosyl)-4-pyrimidone (Id), and various thionucleosides. - O-Phosphorylated 3 -amino-3 -deoxythymidine (2a) and 5 -amino-5 -deoxythymidine (2b)... 

The reaction of 2-pyrimidone (PMOH " CT) (15) with di-iodine in a molar ratio of 1 1 resnlted to the formation of [LOHJ CTl (37) complex. 

Aminopyrimidines have been studied by Albert et al. (1948), and, by relying on the pAj-values at 20° of aminopyridines, there is no doubt that the 4-amino-derivative is protonated on the ring nitrogen N-1 (pAj = 5 69, as compared with pA = 1-23 for unsubstituted pyrimidine). The 2-amino-derivative is a weaker base (pAg = 3 45) and the 5-amino-derivative is weaker still (p/Cg = 2-60). An interesting ultraviolet spectral correlation has recently been pointed out (Albert and Taguchi, 1973) between compounds containing the 2-aminopyrimidinium and 2-pyrimidone structures ([59] and [60]). 

Quaternary salts having structure 51 have been isolated R, and R2 are amino, alkoxy, and thioalkoxy substituents. Except in the case of 2-amino products, dealkylation to give a 2-pyrimidone takes place readily under alkaline conditions.158... 

The luminescence properties of uracil and some of its derivatives confirmed the diketo structure of uracil. Longworth ef al.3i2 have studied the fluororescence342a and phosphorescence of uracil and some of its derivatives. Both 4-ethoxy-2-pyrimidone and 2,4-dimethoxy-pyrimidine have a strong fluorescence at room temperature, and phos-... 

Note that several of these examples produce pyrimidones, analogous to the pyridones previously encountered in Chapter 5. A representative mechanism is shown for the preparation of 2-pyrimidone 10.19, and is simply two consecutive condensations. 

For instance, nitration of 2-pyrimidone 10.20 affords nitropyrimidone 10.21. With doubly-activated systems such as 10.22, nitration to give 10.23 can occur without heating. 

The overall electronic distribution of 2-pyrimidone has a considerable contribution from mesomer 10.20a. 

Cytosine (257) loses ammonia in a two-electron reduction298 with the formation of 2-pyrimidone (258), which, as other pyrimidones,200 is reduced in a one-electron reaction with dimerization. 

Smith et al. have developed a very elegant route to complex polyol structures by sequential dithiane-epoxide coupling reactions (Scheme 7) [16]. Following the work of Tietze [17], 2-silyl-1,3-dithianes 42 are deprotonated with /BuLi in ether and converted into the stable lithium alk-oxides 43 with enantiomerically pure epoxides. A fast 1,4-Brook rearrangement occurs only after the addition of 0.3 equivalents of hexamethyl-phosphoramide (HMPA) or 1,3-dimethylhexahy-dro-2-pyrimidone (DMPU) to the reaction mixture. A new lithiated dithiane 44 that can undergo... 

Pofy-l-vinyluradl (poly-VUr, 10) was also obtained by a free-radical polymerization6). In this case, it should be noted that the formation of substituted dihydrouradl rings occurred via a cydopolymerization mechanism11). y-Ray induced solid-state polymerization of the monomer (9) in high concentration and at low temperature excluded cydopolymerization completely12). Poly-VUr was also prepared by a free-radical polymerization of 2-ethoxy-4-l-vinyl-pyrimidone (ii)8) or 4-ethoxy-l-vinyl-2-pyrimidone (13)iy> followed by acid hydrolysis of the resulting polymers (12) or (14) (Scheme 2). 

The reaction of polymer 31 with the sodium salt of adenine affords stereoregular polyMAOA and the reaction of 31 with theophylline the theophylline derivative 32. Stereoregular polyMAOU was obtained by the reaction of 3/ with the sodium salt of 4-ethoxy-2-pyrimidone followed by add hydrolysis of the resulting polymer 33. The results of the polymer reactions are listed in Table 3. 

The reaction of 2-pyrimidone with vinyl epoxide 16 also takes place under neutral conditions, as oxidative addition of 16 to palladium(O) generates an alkoxide that is sufficiently basic to deprotonate 2-pyrimidone22. In contrast, allyl ester (lS,4/ )-18 demands the use of the potassium phthalimide salt for C-N bond formation33. Similar to the purine /V-allylations with 16 and 18, only the depicted isomers 26 and (15,4f )-27 result. Potassium phthalimide thus represents another ammonia equivalent in palladium(0)-catalyzed allylic substitutions66. 

Similarly, reaction of anti-amino ketoximes with phosgene results in the formation of intermediate 2-pyrimidone Ai-oxide derivatives [785] ... 

Dipolar cycloaddition of the 2-pyrimidone Ai-oxide (10.9) to its tautomer (10.10) results in a spiro compound [785] ... 

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