2 -Pyrimidinones 1-alkoxy

Nucleophilic reagents can also react with 2- and 4-aminopyridines at the carbon atom which carries the amino group in a replacement reaction (e.g. 738 — 739) similar to, but far less facile than, that undergone by chloro and alkoxy compounds, etc. In this way aminopyrimidines can be converted into pyrimidinones by direct acidic or alkaline hydrolysis under rather vigorous conditions. 

Under conditions of the Hilbert-Johnson reaction, the 2,4-dialkoxypyrimidines (29) can furnish the following by-products uracil,13 1-alkyluracil,3-7 1,3-dialkyluracil,19 4-alkoxy-2(lIZ)-pyri-midinone,7 and l-alkyl-4-alkoxy-2(lH)-pyrimidinone.7,20 Thus, for example, 5-chloro-, 5-bromo-, and 5-iodouracil were isolated32- 33 as by-products in the Hilbert-Johnson reaction (in acetonitrile at 20°) of the corresponding 5-halo-2,4-dimethoxypyrimidines and 3,5-di-O-p-toluyl-2-deoxy-D-ribofuranosyl chloride. The formation of 1,3-dimethyluracil and 1,3,5-trimethyluracil as by-products has been observed quite recently19 when the reaction of 2,3,5-tri-O-benzoyl-D-ribofuranosyl chloride with 2,4-dimethoxypyrimidine and 5-methyl-2,4-dimethoxypyrimidine, respectively, was performed in toluene at 70°. 

The Isolation Technique Chromatography. Two alternatives are possible either to isolate the primary Hilbert-Johnson intermediates, i.e., l-peracylglycosyl-4-alkoxy-2(lH)-pyrimidinones, or to treat them with alcoholic hydrogen chloride or alcoholic ammonia and separate the corresponding A-l-glycosyl derivatives of uracil or cytosine. The latter alternative has been used by the earlier authors more frequently because of the higher crystallization ability of... 

In addition to the Hilbert-Johnson reaction, the so-called mercuri process,37 and, less frequently, the cyclization procedure of Shaw et a/.,53 64 have been used for the synthesis of nucleosides and their derivatives. l-Peracylglycosyl-4-alkoxy-2(l//)-pyrimidinones, the intermediates of the Hilbert-Johnson reaction, can be, in principle, prepared 56,56 also by the mercuri process, namely by reaction of 4-ethoxy-2(lZ/)-pyrimidinone chloromercuri salt with the corresponding halogenoses, but this method is of less importance because of the contamination of iV-l-glycosyl derivatives with the 0-2 isomers, namely, with 2-peracylglycosyloxy-4-alkoxypyrimidines. The advantageous features of the mercuri process in comparison with the Hilbert-Johnson reaction might be formulated as follows. 

Other synthons for 1,3-dicarbonyl compounds that have been successfully applied include p-chloro-a,P-unsaturated ketones and aldehydes, P-dimethylamino-a,P-unsaturated ketones (easily obtained from ketones by reaction with DMFDMA), P-alkoxy-enones"" and vinyl-amidinium salts."" Alkynyl-ketones react with 5-alkyl-isothioureas, giving 2-alkylthio-pyrimidines" and propiolic acid reacts with urea to give uracil directly in about 50% yield. "" 1,3-Keto-esters with formamidine produce 4-pyrimidinones"" and C-substituted formamidines with ethyl cyanoacetate give 2-substituted-6-amino -pyrimidinones. In analogy, pyrimidines fused to other rings, for example as in quinazolines, can be made from ortho-aminonitriles " and in general, from P-enamino esters. ... 

Pyrimidinones from l-alkoxy-3-siloxy-2-aza-l,3-dienes and nitriles via heterodiene synthesis... 

The zwitterionic pyridazines (201) and (202), on brief irradiation (quartz filter) in methanol, photo-rearrange to the pyrimidinones (203) and (204) respectively in high yields (60—70%) and (80—90%). " Prolonged irradiation of pyrim-idones (203) in alcoholic media promotes further rearrangement to the 3-alkoxy-l,6-diaza-4-oxo-spiro[4,5]dec-2-enes (205). Apparently, these reactions... 

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