Pyrimidine hydroxy-, ethers

Extraction of soil with hexane acetone (1 1), centrifugation, separation of hexane from acetone/water layer. Extraction of acetone/water phase with chlorofornrdiethyl ether (1 1), solvent exchanged to methanol. Hexane layer contained diazinon, chloroform/diethyl ether fraction contained 2-isopropyl-4-methyl-6-hydroxy-pyrimidine. 

New types of acyclic nucleoside phosphonates (408-412) have been obtained using a multistep synthetic approach based on N-1, O- and S-alkylations of 4-and 2,4-substituted 6-hydroxy and 6-mercaptopyrimidines with diisopropyl 2-(chloroethoxy)methylphosphonate and (R) or (S) - [2-(diisopropylphos-phonyl)methoxy] propyl tosylate. Inhibitory activity against viruses of both the nucleoside phosphonates and the related phosphonic acids was investigated. It was found that the 6[2-(phosphonomethoxy)ethoxy]pyrimidines must bear an (unsubstituted) amino group concomitantly on both C-2 and C-4, or an amino on C-2 and an OH group on C-4, to display antiviral activity. Alkyl ethers are preferred over alkyl thioethers. The compounds of the 6-[2-(phos-phonomethoxy)ethoxy] and 6-[2-(phosphonomethoxy) propoxy]pyrimidine... 

When the vinyl ether 6 was the substrate, AD-mix (3 led to significant amounts of cleavage of the diol product. A change to the pyrimidine-based ligands, in particular the trimethoxy derivative 7 gave high selectivity for the formation of the desired a-hydroxy aldehyde 8 (Scheme 3.7) [255]. 

The reaction has special preparative importance for chlorine-substituted heterocycles. The hydrochloride of the corresponding hydroxy-N-hetero-cycle is usually heated under reflux for several hours with an excess of POCl3, then the excess of POCl3 is distilled off, the residue is decomposed with ice and made alkaline, and the chloro heterocycle is extracted in ether. In this way, 2-chloro-,1060 2-chloro-4-methyl-,1061 2-chloro-4,6-dimethyl-,1062 and 4,6-dichloro-2-methyl-pyrimidine,1063 and 2-chloro-4-methylquinoline,1064 inter alia, have been prepared. 

Additional examples of this fascinating chemistry are listed in Table 1 [9, 10]. For Entries 1-3, the initially formed m-chlorobenzoate product is methanolized to the methyl ether (not shown). Entry 3 represents an attractive synthesis of pyrrolo[3,2-d]pyrimidines [11]. Water is the nucleophile in Entry 4, not m-chlorobenzoate, in a sequence that provides pyrrolo[3,2-c]coumarins [12]. Entry 5 describes the preparation of pyrrolo[3,2-c] [1] benzothi-opyran-4-ones, which is a new ring system and where water has captured the intermediate 3-methylene-2-hydroxy indoline [13]. Entry 6 features the synthesis of pyrrolo[3,2-c]pyrones [14]. Entry 7 describes a similar rearrangement of A-alkyl-A-allenylmethylanihnes with magnesium monoperoxyphthalate (MMPP) to afford 2-vinylindoles [15], This reaction presumably follows the one described earlier, although none of the presumed intermediates could be isolated. 

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