Pyrimidines can be made from 1,3-dicarbonyl compounds and amidines
المؤلف:
Jonathan Clayden , Nick Greeves , Stuart Warren
المصدر:
ORGANIC CHEMISTRY
الجزء والصفحة:
ص770-771
2025-07-15
587
Pyrimidines can be made from 1,3-dicarbonyl compounds and amidines
we met some compounds that interfere in folic acid metabolism and are used as antibacterial agents. One of them was trimethoprim and it contains a pyrimidine ring (black on the diagram). We are going to look at its synthesis briefly because the strategy used is the opposite of that used with the pyrimidine ring in Viagra. Here we disconnect a molecule of guanidine from a 1,3-dicarbonyl compound.
The 1,3-dicarbonyl compound is a combination of an aldehyde and an amide but is very similar to a malonic ester so we might think of making this compound by alkylation of that stable enolate with the convenient benzylic bromide.
The alkylation works fine but it turns out to be better to add the aldehyde as an rather than try to reduce an ester to an aldehyde. The other ester is already at the right oxidation level.
Condensation with ethyl formate (HCO2Et) and cyclization with guanidine gives the pyrimidine ring system but with an OH instead of the required amino group. Aromatic nucleophilic substitution.
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