- Since the use of N, N-diethylaniline hydrochloride in the chlorination
of uric acid with phosphoryl chloride seems to promote the
reaction, a study of the effect of other salts of nitrogenous bases in
the chlorination of uric acid was undertaken. When N, N-diethylaniline
hydrochloride was used in lieu of the free base, the yield of
2, 6, 8-trichloropurine ranged from 41-51%. To further test the use
of amine salts, triethylamine hydrochloride was tested as the amine
hydrochloride. Under completely anhydrous conditions, the yield of
2, 6, 9-trichloropurine ranged from a trace to 1.5%. When known
amounts of water were introduced into the reaction mixture, the
yield of 2, 6, 8-trichloropurine showed a marked increase. The
yields of 2, 6, 8-trichlorpurine ranged from 26.2% when 10 microliters
of water was added to 41.0% when 0.7 milliliters of water was
introduced. In all cases where water was added to the reaction mixture no
uric acid was recovered from the reaction products. Also, in no case
was the water present as such but reacted immediately with the phosphoryl
chloride to yield "pyrophosphoryl chloride."
The results from previous experiments using N, N-diethylaniline
hydrochloride strongly indicated that either the presence or
absence of water had a marked effect on the yield of trichloropurine.
Thus when water was introduced into the chlorination reaction with
uric acid, phosphorus oxychloride, and N, N-diethylaniline hydrochloride,
the yield of 2, 6, 8-trichloropurine dropped to 23.9% with
no recovered uric acid.
Other amine hydrochlorides were tried in the chlorination
reaction with some being made in situ. N, N-dimethyl-p-toluidine
hydrochloride gave only 28.3% of trichloropurine whereas N, N-dimethylaniline
gave a 43.3%yield of 2, 6, 8-trichloropurine.
In general it was found that anhydrous tertiary aromatic amine
hydrochlorides definitely increase the yield of 2, 6, 8-trichloropurine
and aliphatic tertiary amine hydrochlorides with known amounts of
water added also give relatively high yields of trichloropurine. In
all cases, the reaction was much cleaner and free from colored side
products which appear when the free amine is used in the chlorination
of uric acid.