44 
CHEMISTRY: JOHNSON, HILL AND CASE Proc. N. A. S. 
THE ACTION OF DIAZOMETHANE ON URACIL 
By Treat B. Johnson, Arthur J. Hill and Francis H. Case 
Department of Chemistry, Yale University 
Communicated Jan. 25, 1922 
In the course of work now in progress on the determination of consti- 
tution 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 bio- 
chemical research and which gives promise of proving extremely helpful 
in the solution of our problem is the very reactive aliphatic reagent, 
diazomethane : 
II >CH2 
We now find that pyrimidines of the type of uracil interact smoothly 
with this reagent in ether solution at ordinary temperature. The reac- 
tion is productive of nitrogen-alkyl derivatives and in the case of the 
pyrimidine uracil leads to the formation of 1,3 -dime thy luracil in good 
yield. The interaction of uracil and diazomethane may be expressed, 
therefore, as follows: 
NH CO CHsN CO 
I i II 
CO CH + 2N2CH2 = CO CH + 2N2 
I II I II 
NH CH CH3N CH 
The reaction in question is applied by suspending dry, pulverized 
uracil in dry ether containing an excess (4-6 moles) of diazomethane and 
allowing the mixture to stand at ordinary temperature until the uracil com- 
pletely dissolves. The reaction is complete in about 4 days when working 
with uracil in units of one gram. The dimethyl uracil is obtained in the 
form of slender colorless prisms which melt at 121.5° C. (Nitrogen de- 
termination: calculated, 20.03%; found, 19.87%.) 
The study of the behavior of thymine and cytosine is now in progress. 
The results thus far obtained by alkylation with this reagent indicate 
that we may be able to use it with success for the detection of replaceable 
hydrogens in the more complicated pyrimidine and purine glucosides. 
