Direction of hydrolysis of esters of some pyrimidine-5-carboxylic acids

Full text of DOI:10.1007/s10593-007-0228-1

Chemistry of Heterocyclic Compounds, Vol. 43, No. 11, 2007
DIRECTION OF HYDROLYSIS
OF ESTERS OF SOME PYRIMIDINE-
5-CARBOXYLIC ACIDS
S. F. Yan, A. Yu. Ivanov, D. V. Dar'in, P. S. Lobanov, and A. A. Potekhin*
Keywords: pyrimidine-5-carboxylic acids, rearrangement.
Since the first report on the rearrangement of an ester of pyrimidine-5-carboxylic acid [1], this reaction
has been repeatedly described. The alkaline hydrolysis of esters of pyrimidine-5-carboxylic acids 1 may proceed
to give trivial products (pyrimidine-5-carboxylic acids 2) [2, 3] or with rearrangement to give
acetylpyrimidines 3 [4-6].
Me
Me
O
O
CO2Et
CO2H
H2O + NaOH
EtOH
N
N
HN
Me
R
N
R
N
R
N
1a,b
2a,b
3a,b
1–3 a R = Me, b R = NH2
Acids 2 or ketones 3 are formed under similar conditions, while the melting points and spectral
characteristics of acid 2a and ketone 3a as well as of acid 2b and ketone 3b are extremely similar. Schenone et
al. [2] demonstrated the structure of acids 2a,b by their decarboxylation to the corresponding disubstituted
pyrimidines. On the other hand, the evidence for the structure of ketones 3a,b given by various workers [4-6] is
not entirely convincing.
We carried out the hydrolysis of ester 1 under the conditions described by both groups of authors. When
the hydrolysis was carried out in water as described by Schenone et al. [2], we obtained a compound with
mp 150-152°C (154-155°C [2]). When the hydrolysis was carried out in ethanol as described by Danagulyan et
al. [5], we obtained a compound with mp 148-150°C (146-148°C [5]). These two compounds proved identical
with identical NMR spectra. The NMR spectra of a mixture of the two preparations contained one set of signals.
The NMR spectra of our samples were similar to the spectra described in previous work [2, 5]. According to the
13C NMR spectral data (δ, ppm: 24.7, 26.5, 122.1, 159.3, 167.1, 168.5, 169.9), this compound is acid 2a rather
than ketone 3a. A signal for the carbonyl carbon atom in ketone 3a would have been expected at 195-210 ppm.
For example, the signal for the carbonyl carbon atom is found at 201.7 ppm in the 13C NMR spectrum of
5-acetyl-4,6-dichloropyrimidine synthesized in our laboratory according to the procedure of Clark et al. [7].
_______
* Deceased.
__________________________________________________________________________________________
St. Petersburg State University, St. Petersburg 198504, Russia; e-mail: pslob@mail.ru. Translated from
Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1735-1736, November, 2007. Original article submitted
October 5, 2007.
0009-3122/07/4311-1479©2007 Springer Science+Business Media, Inc.
1479

Decarboxylation of the compound obtained in the present work as described by Schenone et al. [2] gave
2,4-dimethylpyrimidine. Judging from the 13C NMR spectrum for the compound given by Danagulyan et al. [5]
(the signal for the carbonyl carbon atom is at 168 ppm), these authors also obtained acid 2a, which was
erroneously assigned the structure of ketone 3a.
13
Analogously, we studied the hydrolysis of ester 1b and obtained only acid 2b, mp >300°C. C NMR
spectrum, δ, ppm: 25.1, 112.7, 162.1, 164.6 167.3, 170.7.
Thus, we may conclude that the rearrangement of esters of pyrimidine-5-carboxylic acids in basic
medium is not general in nature and, at least in the two cases studied in our laboratory, does not occur.
1
The H and 13C NMR spectra were taken on a Bruker DPX 300 spectrometer at 300 and 75 MHz,
respectively, in DMSO-d6 with residual signals as the internal standard at 2.50 ppm for DMSO-d5 in the
1H NMR spectra and 39.7 for DMSO-d6 in the 13C NMR spectra.
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