Russian Journal of General Chemistry, Vol. 74, No. 1, 2004, pp. 146 147. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 1, 2004,
pp. 159 160.
Original Russian Text Copyright
2004 by Erkin, Krutikov.
LETTERS
TO THE EDITOR
Formylation of 6-Aminouracil with Vilsmeier Reagent
A. V. Erkin and V. I. Krutikov
St. Petersburg Technological Institute, St. Petersburg, Russia
Received January 16, 2003
Oxopyrimidine-5-carbaldehydes I and some of their
derivatives (azomethines, hydrazones) show promise
as synthetic precursors of antitumor agents [1, 2].
Aldehydes I are usually synthesized by the Reimer
Tiemann reaction [3], controlled oxidation of 5-hy-
droxymethylpyrimidines [4], or Vilsmeier reaction.
The latter reaction can be accompanied by exchange
chlorination of oxo groups of the pyrimidine ring.
For example, heating of 6-aminouracil II with POCl3
in DMF yields 6-amino-2,4-dichloro-5-formylpyrimi-
dine [5]. At the same time, there are indications in the
literature [6] that Vilsmeier formylation of amine II
can be performed so as to leave the oxo groups intact.
dropwise with vigorous stirring to a suspension of
12.7 g of amine II in 25 ml of absolute DMF over a
period of 1 h, avoiding warm-up of the mixture above
20 C. After adding the whole amount of POCl , the
3
solidified mixture was crushed mechanically and
heated on a boiling water bath for 2 h. After cooling,
the mixture was transferred onto ice and ground to
obtain a suspension. The suspension was neutralized
with 40% aqueous NaOH at a temperature not exceed-
ing 20 C, and the precipitate was filtered off, washed
with water, and suspended in 5% aqueous NaOH.
The undissolved residue was filtered off, thoroughly
washed with water, suspended in 100 ml of water, and
acidified with concentrated HCl to pH 4 5. The pre-
cipitate was filtered off, washed with water, refluxed
successively with 100 ml of water and 100 ml of
ethanol, and vacuum-dried over sodium pentoxide at
To develop a procedure for preparing 6-aminoura-
cil-5-carbaldehyde III, we studied the reaction of
amine II with Vilsmeier reagent at 90 100 C:
O
O
80 C. Yield 6.5 g (42%), R 0.69, mp >300 C. IR
f
2
1
4
1
spectrum, , cm : 1739 (C =O), 1674 (C =O). H
HN
HN
O
POCl3
Me NCHO
NMR spectrum, , ppm: 7.36 s (1H, NH ), 9.19 s (1H,
2
2
O
N
NH2
O
N
H
NH2
NH ), 9.66 s (1H, CHO), 10.78, 10.83 d (2H, NH).
2
+
H
Mass spectrum, m/z (I , %): 155 [M] (52.5), 127
rel
+
+
[M
CHO] (100), 68 [M HCNO NH ] (84.5).
II
III
2
Found, %: C 38.58; H 2.97; N 26.44. C H N O .
5
5
3
3
Because of the low solubility of amine II in abso-
lute DMF, the reaction was performed in a hetero-
geneous system. In six experiments at a fixed contact
time (2 h), we obtained chromatographically identical
products identified by elemental analysis and spectros-
copy as 6-aminouracil-5-carbaldehyde III. The IR
spectrum of III contains stretching bands of the oxo
Calculated, %: C 38.71; H 3.22; N 27.09.
The IR spectrum was recorded on a Shimadzu
Hyper-IR spectrometer (mull in mineral oil). The H
NMR spectrum was recorded on a Bruker AMX-400
1
spectrometer (400 MHz, DMSO-d ) relative to residu-
6
al solvent protons. The mass spectrum was taken on
a Kratos MS-30 spectrometer (direct sample inlet,
ionizing electron energy 70 eV, ion source tempera-
ture 200 C). Elemental analysis was performed with
a Carlo Erba 1106 analyzer. The compound purity
was checked by TLC on Silufol UV-254 plates in
the system chloroform methanol, 3 : 1, with UV
development.
1
groups of the pyrimidine ring at 1739 1674 cm .
1
The H NMR spectrum contains a formyl proton sig-
nal at 9.66 ppm. The mass spectrum contains the
molecular peak.
6-Aminouracil-5-carbaldehyde III (general proce-
dure). Freshly distilled POCl (18.3 ml) was added
3
1
070-3632/04/7401-0146 2004 MAIK Nauka/Interperiodica
Erkin
