The Action of Diazomethane on Uracil.

In the course of work now in progress on the determination of constitution of nucleic acid and its primary hydrolytic products-neucleotides and neucleosides-it has finally become necessary to develop and utilize a new method for introducing methyl radicals into pyrimidine and purine combinations. The alkylation methods generally employed for bringing about such changes, namely, by interaction of alkali or silver salts with methyl iodide and dimethyl sulphate, have not proven satisfactory, and it has become necessary to turn to a reagent that will interact directly with the pyrimidine nucleus at a low temperature and in other solvents than water or alcohol. A reagent which has found little use thus far in biochemical research and which gives promise of proving extremely helpful in the solution of our problem is the very reactive aliphatic reagent, diazomethane: N 11>CH2 N We now find that pyrimidines of the type of uracil interact smoothly with this reagent in ether solution at ordinary temperature. The reaction is productive of nitrogen-alkyl derivatives and in the case of the pyrimidine uracil leads to the formation of 1,3-dimethyluracil in good yield. The interaction of uracil and diazomethane may be expressed, therefore, as follows: NH-CO CH3N CO I I CO CH + 2N2CH2= CO CH + 2N2 I 11 11 NH-CH CH3N CH