4.6- Dimethyl-2 -pyrimidinone, solution

After selective generation of the syn- or anH -enolate of an amide, it is usually reacted with a haloalkane, often the iodide. Allylic and benzylic bromides also react satisfactorily, and dimethyl and diethyl sulfate have also been used in some cases. A solution of the alkylating agent in an ethereal solvent, usually tetrahydrofuran, is added to the enolate, usually at low temperature. A polar, aprotic cosolvent, such as hexamethylphosphoric triamide, is frequently used as an additive in the alkylation step. The use of this suspected carcinogen is prohibited in some countries, which limits the usefulness of many of the reactions described below. However, similarly effective in many cases are some ureas, such as the commercially available 1,3-dimethyl-3,4,5,6-tetrahydro-2(l//)-pyrimidinone (DMPU)12. 

The effect of a 5-substituent on the tautomeric equilibrium of 4-pyrimidinones 53 (R1 = Me R2 = H, Me, MeO, COOEt, CONH2, CN R3 = H) was studied using their acidic and basic ionization constants and the results were confirmed by UV spectroscopy (74CPB1239). It was shown that all these compounds exist in aq. solution as an almost equimolar mixture of two oxo forms with the fraction of the hydroxy form not exceeding 4%. 4,6-Dimethyl-2(l//)-pyrimidinone and 6-methyl-4-pyrimidinone exist predominantly in the lactam form in solution (80JST(62)47, 84H(22)2591). 

A problem with this methodology is that only one of the three alkyl groups is transferred to the unsaturated carbonyl compound. A solution to this uses the radical generated from the boronic ester, itself derived from hydroboration with catecholb-orane 8. Treatment of the boronic ester with oxygen and 1,3-dimethyl-hexahydro-2-pyrimidinone (DMPU) in the presence of the a,3-unsaturated aldehyde or ketone gives the desired radical addition product, with transfer of the S-alkyl group. Thus, cyclohexene was converted to l-cyclohexyl-3-pentanone 24 using this chemistry (5.38). 

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