Chemical Properties of 6-Methyluracil-5-carbaldehyde Oxime

Article abstract of DOI:10.1134/S1070428019090045

Oxidative chlorination of 6-methyluracil-5-carbaldehyde oxime in a two-phase system gave 7V-hydroxy-6-methyluracil-5-carboximidoyl chloride, and its bromination afforded ipso-substitution products, 5-bromo-6-methyluracil and 5,5-dibromo-6-hydroxy-6-methyl-5,6-dihydrouracil. The reaction of the title compound with acetic anhydride led to the formation of 6-methyluracil-5-carbonitrile or O-acetyl derivative, depending on the temperature. 7V-Hydroxy-6-methyluracyl-5-carboximidoyl chloride reacted with acetic acid at 100°C or with potassium iodide in boiling acetone to produce uracil-5-hydroxamic acid which was converted with high yields into the corresponding methyl ester and hydroximic acid amide. Quaternary ammonium salts were obtained by reactions of N-hydroxy-6-methyluracil-5-carboximidoyl chloride with pyridine and 1-methyl-1H-imidazole.

Full text of DOI:10.1134/S1070428019090045

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2019, Vol. 55, No. 9, pp. 1287–1294. © Pleiades Publishing, Ltd., 2019.
Russian Text © The Author(s), 2019, published in Zhurnal Organicheskoi Khimii, 2019, Vol. 55, No. 9, pp. 1367–1375.
Chemical Properties of 6-Methyluracil-5-carbaldehyde Oxime
I. B. Chernikovaa,* S. L. Khursana, L. V. Spirikhina, and M. S. Yunusova
a Ufa Institute of Chemistry, Ufa Federal Research Center, Russian Academy of Sciences, Ufa, Bashkortostan, Russia
*e-mail: inna.b.chernikova@yandex.ru
Received February 11, 2019; revised February 28, 2019; accepted May 15, 2019
Abstract—Oxidative chlorination of 6-methyluracil-5-carbaldehyde oxime in a two-phase system gave
N-hydroxy-6-methyluracil-5-carboximidoyl chloride, and its bromination afforded ipso-substitution products,
5-bromo-6-methyluracil and 5,5-dibromo-6-hydroxy-6-methyl-5,6-dihydrouracil. The reaction of the title com-
pound with acetic anhydride led to the formation of 6-methyluracil-5-carbonitrile or O-acetyl derivative,
depending on the temperature. N-Hydroxy-6-methyluracyl-5-carboximidoyl chloride reacted with acetic acid at
100°C or with potassium iodide in boiling acetone to produce uracil-5-hydroxamic acid which was converted
with high yields into the corresponding methyl ester and hydroximic acid amide. Quaternary ammonium salts
were obtained by reactions of N-hydroxy-6-methyluracil-5-carboximidoyl chloride with pyridine and 1-methyl-
1H-imidazole.
Keywords: 6-methyluracil, 6-methyluracil-5-carbaldehyde oxime, halogenation, nucleophilic substitution,
cycloaddition.
DOI: 10.1134/S1070428019090045
Chemical modifications of pyrimidine bases are
important for the synthesis of biologically active com-
pounds. Synthetic transformations of pyrimidines gave
rise to new promising medicines. In recent years, the
chemistry of 5-substituted pyrimidines has developed
especially extensively. These compounds not only
exhibit physiological activity but also can be used as
starting materials for the synthesis of various pyrimi-
dine derivatives. Therefore, development of methods
of functionalization of uracil with the goal of obtaining
potentially biologically active compounds and study of
their chemical properties are important problems.
uracil-5-carbaldehyde oxime 1 [10] and chemical
transformations of the halogenation product with
a view to obtaining potential biologically active
compounds.
Compound 1 remained unchanged in the system
KCl/H2O2–20% H2SO4 at room temperature [5]. The
bromination of 1 with potassium bromide under
similar conditions gave ipso-substitution product,
5-bromo-6-methyluracil (2), in 85% yield. Compound
2 was also obtained by us previously in the bromina-
tion of 5-formyl- and 5-hydroxymethyl-6-methyl-
uracils [6]. In order to rule out the possibility of initial
formation of 6-methyl-5-formyluracil from compound
1, the reaction was carried out under similar conditions
in the absence of KBr. In this case, initial oxime 1 was
recovered from the reaction mixture. It is known that
oximes react with molecular halogens (Cl2, Br2) to
6-Methyluracil is a component of a number of
drugs, which possesses a broad spectrum of physio-
logical activity [1–4]. In continuation of our studies on
halogenation of 6-methyluracil and its derivatives
[5–9], herein we report the halogenation of 6-methyl-
Scheme 1.
O
O
O
Br
Br
i
ii
HN
HN
HN
Br
NOH
2
+
OH
O
N
H
Me
O
N
H
Me
O
N
H
Me
2
1
3
Reagents and conditions: i: KBr (2 equiv), 33% H2O2 (3 equiv), 20% H2SO4, room temperature, 5 h, (yield 85%);
ii: 10 or 38% HBr (3 equiv), 33% H2O2 (4 equiv), CH2Cl2, room temperature, 3 h; 2 (40–43%), 3 (38–51%).
1287

CHERNIKOVA et al.
1288
Scheme 2.
O
Cl
H+
i
HN
N
OH2
OH
–H+
O
Cl
O
Cl
O
NHOH
O
O
N
H
Me
HN
O
NOH
HN
NHOH
HN
OH
Me
–HCl
O
Cl
N
H
Me
O
N
H
O
N
H
Me
ii
H2O
4
5
HN
N
OH
I
O
N
H
Me
Reagents and conditions: i: AcOH/H2O 100°C, 1 h; ii: KI (3 equiv), Me2CO/H2O, reflux, 3 h.
give the corresponding hydroximoyl halides [11]; how-
ever, oxime 1 failed to react under these conditions.
For comparison, benzaldehyde oxime was reacted with
molecular chlorine at room temperature; as a result,
76% of benzoic acid was obtained. According to
published data [12], the chlorination at 0°C gives
benzohydroximoyl chloride (70%). The chlorination of
the latter with Cl2 at room temperature produced
benzoic acid (83%).
droximoyl chlorides [13], compound 4 failed to react
on heating in water in the absence of acetic acid.
Interestingly, hydroxamic acid 5 was also formed in
70% yield when compound 4 was heated with excess
potassium iodide in boiling acetone. A probable
mechanism of formation of 5 is shown in Scheme 2.
In order to obtain 6-methyluracil-5-carbonitrile
oxide and convert it to furoxan, compound 4 was
treated with a mixture of triethylamine and methanol at
room temperature. However, the product was hydrox-
imic acid methyl ester 6 (yield 80%; Scheme 3). When
the reaction was carried out in methanol containing no
triethylamine, the initial chloride was recovered from
the reaction mixture. Syntheses of hydroximic acid
methyl esters by reactions with sodium alkoxides
[14–15] or CaCO3 [16] or in a MeOH–H2O–dioxane
mixture at 160°C [17] have been reported; however,
these reactions are likely to follow different mecha-
nisms.
As we showed previously, the halogenation of 1
with HCl–H2O2 in methylene chloride at room tem-
perature in 3 h afforded 90% of N-hydroxy-6-methyl-
uracil-5-carboximidoyl chloride (4) [10]. However, the
bromination of 1 with 38 or 10% HBr in the presence
of 33% H2O2 in a two-phase system led to the forma-
tion of ipso-substitution products, 5-bromo-6-methyl-
uracil (2) and 5,5-dibromo-6-hydroxy-6-methyl-5,6-
dihydrouracil (3), in low yields (Scheme 1).
By treatment of chloride 4 with acetic acid at 100°C
(1 h) we obtained hydroxamic acid 5 in a good yield
(Scheme 2). In contrast to published data for hy-
The reaction of 4 with pyridine gave quaternary
pyridinium salt 7. Analogous benzimidazolium salt
Scheme 3.
O
N
O
NH2
NOH
O
X
Cl–
iv
i–vi
HN
NOH
HN
HN
NOH
4
91%
O
N
H
Me
O
N
H
Me
O
N
H
Me
6–10
7
9
N
N
N
N
Cl–
6, X = MeO; 7, X =
; 8, X =
; 9, X = H2N; 10, X =
.
Cl–
Me
Reagents and conditions: i: Et3N (2 equiv), MeOH, room temperature, 6 h (6, yield 80%); ii: pyridine, room temperature, 6 h (7,
82%); iii: N-methylimidazole, room temperature, 6 h (8, 77%); iv: 29% aq. NH3, room temperature, 2 h (9, 70%); v: piperidine, room
temperature, 6 h (10, 70%); vi: pyridine (2 equiv), MeOH, room temperature, 6 h (7, 83%).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

CHEMICAL PROPERTIES OF 6-METHYLURACIL-6-CARBALDEHYDE OXIME
1289
Scheme 4.
O
NH2
NOH
NH3
HN
O
Cl
O
O–
O
O
N
H
Me
N
O–
R3N
9
6
HN
N
HN
–Cl–
–R3NH
O
OMe
O
N
H
Me
O
N
H
Me
MeOH
4a
HN
NOH
N
H
Me
4
O
N
Pyridine
–C5H5N·HCl
Pyridine
C5H5N·HCl
O–
4a
7
HN
N
O
N
Me
H
4b
8 was formed in a solution of 4 in 1-methyl-1H-
imidazole. Treatment of 4 or 7 with aqueous ammonia
for 2 h afforded amide oxime 9, and amide oxime 10
was obtained in the reaction of 4 with piperidine
(Scheme 3).
tions with primary and secondary amines were re-
ported to produce amide oximes [18]. Presumably, the
only known example of reactions with nitrogen-con-
taining aromatic compounds is the reaction of amino-
pyridine with carboxyethylhydroxamoyl chloride,
which gave a bicyclic compound [20]. Although the
path of product formation was not discussed, the reac-
tion obviously involves intermediate nitrile oxide.
It should be noted that, unlike the reaction of 4 with
triethylamine and methanol leading to methyl ester 6,
compound 4 reacted with 2 equiv of pyridine in metha-
nol at room temperature to produce ammonium salt 7.
The structure of all isolated compounds was deter-
Our mechanistic views were confirmed by theore-
tical modeling of the observed transformations. The
most favorable structures and energies of the initial
reactants, transition states, and final products of reac-
tions i and vi in Scheme 3 were calculated in the
TPSSTPSS/6-311+G(d,p) approximation including
solvent effect (MeOH) in terms of the IEFPCM-SMD
polarized continuum model. The energy profile of
these transformations is shown in Fig. 1. The rate
constants of the elementary steps outlined in Fig. 1
were estimated using the Eyring equation, and the
competing reaction rate ratios (Py vs. MeOH, Et3N vs.
MeOH) were calculated. Under the v conditions, nitrile
1
mined by NMR spectroscopy, including H–1H COSY,
13C–1H HSQC and HMBC, and 15N–1H HSQC and
HMBC experiments. The experimental data were also
confirmed by theoretical calculations.
Obviously, compounds 6–10 are formed through
intermediate nitrile oxide 4a, which is typical of
hydroximoyl chlorides in alkaline medium [18]. The
described reactions are likely to follow the mechanism
outlined in Scheme 4. Nitrile oxide 4a is capable of
undergoing dimerization to furoxan (this process gen-
erally accompanies to a greater or lesser extent the
formation of nitrile oxides [19] or reacting with a nu-
cleophile present in the reaction mixture (methanol,
pyridine, N-methylimidazole, ammonia, piperidine).
However, our results suggest that under the given con-
ditions dimerization of 4a to furoxan does not occur.
oxide 4a reacts exclusively with pyridine, wPy/wMeOH
=
3.1×105. Zwitterion ZW1 thus formed (Fig. 1) is fairly
stable: the change of the Gibbs free energy in the
reversible decomposition of ZW1 into pyridine and
uracil 4a is 54.3 kJ/mol, which is sufficiently high for
the reversible reaction to be incapable of competing
with the fast, obviously diffusion-controlled, protona-
tion of ZW1 leading to compound 7 (Scheme 4).
The most widely known reaction of nitrile oxides is
[3+2]-cycloaddition. Much less data are available for
their reactions with nucleophiles. In particular, reac-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

CHERNIKOVA et al.
1290
TS3
MeOH
133.6
MeOH···Py
125.8
115.9
MeOH···NEt3
TS2
104.1
TS1
94.5
ZW2
84.5
ZW1
40.2
0.0
0.0
Et3N + 4a
0.0
MeOH + 4a
6
Py + 4a
–7.2
Pyridine
Triethylamine
Methanol
Fig. 1. Gibbs free energy profiles for the reactions of nitrile oxide 4a with nucleophiles according to TPSSTPSS/6-311+G(d,p)/
IEFPCM-SMD calculations. For the reaction with methanol, energies of transition states are given with account taken of association
of methanol with pyridine and triethylamine, as well as for unassociated methanol; ZW1 is a zwitterion derived from pyridine and 4a
(4b), ZW2 is a zwitterion derived from triethylamine and 4a (like 4b), and TS is a transition state.
A different situation is observed under the i condi-
tions. Though the ratio of the reaction rates of 4a with
Et3N and MeOH favors the reaction with the former,
with N-benzylmaleimide was much simpler. This reac-
tion, as well as the reaction of 4a with methanol, is
exothermic and hence virtually irreversible, ΔG1 =
91.7 kJ/mol, ΔrG = –60.3 kJ/mol; the calculated struc-
tures and energies of all species involved in the reac-
tion are available from the authors. The ratio of the
rates of the competing reactions, w[3+2]/wMeOH = 104,
indicates that the [3+2]-cycloaddition predominates
over the reaction of 4a with the solvent, which is con-
sistent with the experimental data.
w
Et3N/wMeOH = 120, zwitterion ZW2 thus formed is
thermodynamically unstable. The reverse decomposi-
tion of ZW2 is characterized by a low ΔG value,
19.6 kJ/mol (Fig.1), and hence by a high rate constant,
k = 2.3×109 s–1 (estimated by the Eyring equation).
Obviously, the rate of diffusion-controlled stabilization
of ZW2 should be considerably lower that the rate of
its reversible decomposition, and the main direction of
the irreversible transformation of 4a should be its
reaction with methanol to produce ester 6, which is
observed experimentally.
According to [21], oxime 1 in boiling acetic anhy-
dride was converted to 5-cyano-6-methyluracil (12).
However, by heating compound 1 in acetic anhydride
at 70–80°C we obtained O-acetyl derivative 13
(Scheme 6). As we showed previously, oxime 1 readily
undergoes acylation [10], which is typical of the syn
isomer. The fact that the reaction of 1 with acetic anhy-
dride at 70–80°C afforded O-acetyl oxime 13 in a good
yield is likely to be related to its syn configuration.
The reaction of 4 with N-benzylmaleimide in the
presence of triethylamine gave [3+2]-cycloaddition
product 11 (Scheme 5). The results suggest that nitrile
oxide 4a is a weak dienophile. Theoretical DFT
analysis of competing processes in the reaction of 4a
Scheme 5.
Scheme 6.
O
O
O
O
N
O
CN
Me
i
i
ii
HN
HN
HN
NOAc
4
1
N
87%
56%
85%
Ph
O
N
H
O
N
H
Me
O
N
H
Me
O
12
13
11
Reagents and conditions: i: Et3N (2 equiv), N-benzylmale-
Reagents and conditions: i: Ac2O, reflux, 0.5 h;
ii: Ac2O, 70–80°C, 1 h.
imide (2 equiv), MeOH, room temperature, 5 h.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

CHEMICAL PROPERTIES OF 6-METHYLURACIL-6-CARBALDEHYDE OXIME
1291
(a)
(b)
Fig. 2. Most stable isomers of compounds (a) 1 and (b) 4 (b) according to TPSSTPSS/6-311+G(d,p)/IEFPCM-SMD calculations with
methanol as solvent.
1
This assumption was verified by TPSSTPSS/
6-311+G(d,p)/IEFPCM-SMD calculations of the Gibbs
free energies of all possible isomers of 1 and 4 in three
solvents with different polarities (pyridine, methanol,
water). In fact, the overall population of the syn
isomers was 0.96 (H2O), 0.98 (MeOH), and ~1 (Py);
the structures of the most stable isomers with a popula-
tion higher than 0.93 (1) and 0.88 (4) are shown in
Fig. 2. The oxime group in compound 1 is coplanar to
the pyrimidine ring, whereas the NOH group of 4 is
turned through an angle of 68° with respect to the
pyrimidine ring plane. These findings rationalize the
high yield of 13 in the acetylation of 6-methyluracil-5-
carbaldehyde oxime.
determined from the F1 projection of the H–15N
HMBC spectra and are given relative to ammonia. The
mass spectra were obtained on a Shimadzu LCMS-
2010 EV quadrupole spectrometer [samples were dis-
solved in acetonitrile–chloroform and introduced with
a syringe pump; eluent acetonitrile–water (95:5), flow
rate 0.1 mL/min); positive and negative ion detection
at a capillary voltage of 4.5 and –3.5 kV, respectively];
atmospheric pressure chemical ionization mass spectra
were recorded at an interface capillary voltage of 25 to
–25 V; interface temperature 250°C, heater tempera-
ture 200°C, vaporizer temperature 230°C; nebulizer
gas nitrogen, flow rate 2.5 L/min. Elemental analyses
were performed with a Euro 3000 analyzer. The
melting points were measured in glass capillaries.
Analytical TLC was performed using Sorbfil plates
(Russia); eluent chloroform–methanol (9:1); spots
were detected by treatment with a solution of 4-me-
thoxybenzaldehyde.
Thus, the oxidative bromination of oxime 1 gives
ipso-substitution products, 5-bromo-6-methyluracil (2)
and 5,5-dibromo-6-hydroxy-6-methyl-5,6-dihydro-
uracil (3). The reaction of hydroximoyl chloride 4 with
methanol in the presence of triethylamine yields
methyl ester 6, quaternary salts 7 and 8 are readily
formed in the reactions of 4 with pyridine and
N-methylimidazole, and amide oximes 9 and 10 are
products of the reactions of 4 with aqueous ammonia
and piperidine, respectively. Amide 9 is also formed in
the reaction of 7 with aqueous ammonia. The reaction
of oxime 1 with acetic anhydride leads to the forma-
tion of nitrile 12 or O-acetyl derivative 13, depending
on the temperature.
Bromination of oxime 1. Oxime 1, 0.20 g
(1.2 mmol), was dissolved in 2.00 mL of methylene
chloride, 0.56 mL of 38% HBr (3.6 mmol) or 2.70 mL
of 10% HBr (3.6 mmol) was added with stirring at
room temperature, and 0.48 mL of 33% H2O2
(4.8 mmol) was then added dropwise. The mixture was
stirred for 3 h at room temperature, and the precipitate
was filtered off, washed with distilled water, and dried.
We thus isolated 0.10 g (43%) or 0.09 g (40%) of
5-bromo-6-methyluracil (2) whose physicochemical
characteristics were consistent with those given in [5].
The filtrate was evaporated to obtain 0.14 g (40%) or
0.13 g (38%) of 5,5-dibromo-6-hydroxy-6-methyl-5,6-
dihydrouracil (3) [5].
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded at
298 K from solutions in DMSO-d6 on a Bruker
Avance-III 500 spectrometer operating at 500.13 (1H),
125.76 (13C), or 50.68 MHz (15N) using a PABBO
5-mm Z-gradient probe. The 15N chemical shifts were
N-Hydroxy-6-methyl-2,4-dioxo-1,2,3,4-tetrahy-
dropyrimidine-5-carboxamide (5). A suspension of
0.20 g (1.0 mmol) of hydroximoyl chloride 4 in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 55 No. 9 2019

CHERNIKOVA et al.
1292
2.00 mL of acetic acid was stirred for 1 h at 100°C.
Alternatively, a suspension of 0.20 g (1.0 mmol) of 4
in 2.00 mL of acetone containing 0.50 g (3.0 mmol) of
potassium iodide was refluxed for 5 h. The mixture
was evaporated, and the residue was repeatedly
washed with chloroform, dried, and recrystallized from
methanol. Yield 0.15 g (83%) or 0.13 g (70%), white
139.76 (C7), 144.54 (C2′, C6′), 148.23 (C4′), 149.99
(C2), 158.65 (C6), 162.46 (C4). 15N NMR spectrum, δN,
ppm: 146.27 (N1), 156.90 (N3), 209.60 (NOH), 354.90
(N1′). Found, %: C 43.81; H 4.02; Cl 11.85; N 18.79.
C11H11ClN4O3·H2O. Calculated, %: C 43.94; H 4.36;
Cl 11.79; N 18.63. M 300.70.
3-[(Hydroxyimino)(6-methyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)methyl]-1-methyl-1H-
imidazol-3-ium chloride (8). A suspension of 0.2 g
(1.0 mmol) of 4 in 2.0 mL of N-methylimidazole was
stirred for 6 h at room temperature. The precipitate was
filtered off, washed with a 1% aqueous solution of
potassium carbonate (pH 8), distilled water, and
acetone, dried, and recrystallized from methanol. Yield
0.23 g (77%), white crystals, mp 224–226°C (decomp.;
1
crystals, mp >290°C (decomp., MeOH). H NMR
spectrum, δ, ppm: 2.14 s (3H, CH3), 9.73 s (1H, NOH),
11.19 s (1H, 1-H), 11.29 s (1H, 3-H). 13C NMR spec-
trum, δC, ppm: 17.83 (CH3), 105.58 (C5), 150.51 (C4),
155.53 (C7), 161.61 (C2), 163.21 (C6). Mass spectrum,
m/z (Irel, %): 184 (87) [M – H]–, 166 (100) [M –
H – H2O]–. Found, %: C 38.79; H 3.75; N 22.79.
C6H7N3O4. Calculated, %: C 38.92; H 3.81; N 22.70;
M 185.14.
1
from MeOH). H NMR spectrum, δ, ppm: 2.17 s (3H,
CH3), 3.88 s (3H, NCH3), 7.70 d (1H, 5′-H, J =
7.8 Hz), 7.99 d (1H, 4′-H, J = 7.8 Hz), 9.70 s (1H,
2′-H), 11.44 s (2H, 1-H, 3-H), 13.05 s (1H, NOH).
13C NMR spectrum, δC, ppm: 17.65 (CH3), 36.90
(NCH3), 102.00 (C5), 122.66 (C5′), 123.44 (C4′), 134.27
(C2′), 138.58 (C7), 151.14 (C2), 158.36 (C6), 163.52
(C4). 15N NMR spectrum, δN, ppm: 143.10 (N1),
166.90 (N3), 173.90 (N3′), 183.90 (NOH), 349.00 (N1′).
Found, %: C 39.37; H 4.36; Cl 11.75; N 23.17.
C10H12ClN5O3·H2O. Calculated, %: C 39.55; H 4.65;
Cl 11.67; N 23.06; M 303.70.
Methyl N-hydroxy-6-methyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidine-5-carboximidate (6). Triethyl-
amine, 0.28 mL (2.0 mmol), was added in one portion
to a mixture of 0.20 g (1.0 mmol) of 4 and 2.00 mL of
methanol, and the mixture was stirred for 6 h at room
temperature. The mixture was evaporated, the viscous
residue was ground with chloroform, and the precip-
itate was filtered off, repeatedly washed with chloro-
form, dried, and recrystallized from methanol. Yield
0.16 g (80%), white crystals, mp 195–197°C (decomp.;
1
from MeOH). H NMR spectrum, δ, ppm: 2.05 s (3H,
N-Hydroxy-6-methyl-2,4-dioxo-1,2,3,4-tetrahy-
dropyrimidine-5-carboximidamide (9). A suspension
of 0.20 g (1.0 mmol) of 4 or of 0.20 g (0.7 mmol) of 7
in 2.00 mL of 29% aqueous ammonia was stirred for
2 h at room temperature. The precipitate was filtered
off, washed with distilled water and acetone, dried, and
recrystallized from methanol. Yield 0.13 g (70%) or
0.11 g (91%), white crystals, mp > 220°C (decomp.;
CH3), 3.50 s (3H, OCH3), 9.75 s (1H, NOH), 11.10 s
(1H, 1-H), 11.40 s (1H, 3-H). 13C NMR spectrum, δC,
ppm: 17.40 (CH3), 55.37 (OCH3), 102.55 (C5), 150.33
(C6), 150.98 (C2), 155.04 (C7), 163.36 (C4). Mass spec-
trum, m/z (Irel, %): 198 (100) [M – H]–, 166 (25) [M –
H – CH3OH]–. Found, %: C 42.09; H 4.35; N 21.20.
C7H9N3O4. Calculated, %: C 42.21; H 4.55; N 21.10.
M 199.16.
1
from MeOH). H NMR spectrum, δ, ppm: 1.98 s (3H,
1-[(Hydroxyimino)(6-methyl-2,4-dioxo-1,2,3,4-
tetrahydropyrimidin-5-yl)methyl]pyridin-1-ium
chloride (7). A suspension of 0.20 g (1.0 mmol) of 4 in
2.00 mL of pyridine or in 2.00 mL of methanol
containing 0.16 mL (2.0 mmol) of pyridine was stirred
for 6 h at room temperature. The precipitate was
filtered off, washed with a 1% aqueous solution of
potassium carbonate (pH 8), distilled water, and
acetone, dried, and recrystallized from methanol. Yield
0.24 g (82%) or 0.25 g (83%), white crystals, mp 185–
CH3), 9.15 s (3H, NOH, NH2), 10.99 s (2H, 1-H, 3-H).
13C NMR spectrum, δC, ppm: 17.27 (CH3), 106.08
(C5), 147.19 (C7), 151.07 (C2), 152.55 (C6), 163.33
(C4). Mass spectrum, m/z (Irel, %): 183 (100) [M – H]–,
165 (12) [M – H – H2O]–, 166 (9) [M – H – NH3]–.
Found, %: C 39.02; H 4.26; N 30.51; C6H8N4O3. Cal-
culated, %: C 39.13; H 4.38; N 30.42. M 184.15.
5-[(Hydroxyimino)(piperidin-1-yl)methyl]-6-
methylpyrimidine-2,4(1H,3H)-dione (10). A suspen-
sion of 0.20 g (1.0 mmol) of 4 in 2.00 mL of piperidine
was stirred for 6 h at room temperature. The precipitate
was filtered off, washed with a 1% aqueous solution of
potassium carbonate (pH 8), distilled water, and
acetone, dried, and recrystallized from methanol. Yield
0.17 g (70%), white crystals, mp 176–178°C (decomp.;
1
187°C (decomp.; from MeOH). H NMR spectrum, δ,
ppm: 2.42 s (3H, CH3), 8.28 t (2H, 3′-H, 5′-H, J =
7.2 Hz), 8.79 t (1H, 4′-H, J = 7.2 Hz), 9.20 d (2H,
2′-H, 6′-H, J = 7.2 Hz), 11.50 s (1H, 1-H), 11.90 s (1H,
3-H), 13.31 s (1H, NOH). 13C NMR spectrum, δC,
ppm: 17.55 (CH3), 100.53 (C5), 127.24 (C3′, C5′),
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CHEMICAL PROPERTIES OF 6-METHYLURACIL-6-CARBALDEHYDE OXIME
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1
from MeOH). H NMR spectrum, δ, ppm: 1.44 s (4H,
8.33 s (1H, 7-H), 11.41 s (1H, 1-H), 11.53 s (1H, 3-H).
13C NMR spectrum, δC, ppm: 19.65 (C10), 19.85 (C9),
100.31 (C5), 150.48 (C6), 152.22 (C7), 156.98 (C2),
163.22 (C4), 168.79 (C8). Found, %: C 45.41; H 4.15;
N 19.99. C8H9N3O4. Calculated, %: C 45.50; H 4.30;
N 19.90. M 211.17.
3′-H, 5′-H), 1.47 s (2H, 4′-H), 1.90 s (3H, CH3),
2
3
2.96 d.d (2H, 2′-H, 6′-H, J = 12.8, J = 4.3 Hz),
3.03 d.d (2H, 2′-H, 6′-H, 2J = 12.8, 3J = 5.2 Hz), 9.02 s
(1H, NOH), 11.02 s (2H, 1-H, 3-H). 13C NMR spec-
trum, δC, ppm: 17.00 (CH3), 24.70 (C4′), 25.50 (C3′,
C5′), 46.88 (C2′, C6′), 104.08 (C5), 150.52 (C6), 151.40
(C7), 153.22 (C2), 161.91 (C4). Found, %: C 52.28;
H 6.11; N 22.38. C11H16N4O3. Calculated, %: C 52.37;
H 6.39; N 22.21. M 252.27.
ACKNOWLEDGMENTS
The spectral studies and DFT calculations were
performed using the facilities of the “Chemistry” joint
center, Ufa Institute of Chemistry, Ufa Federal
Research Center, Russian Academy of Sciences.
5-Benzyl-3-(6-methyl-2,4-dioxo-1,2,3,4-tetrahy-
dropyrimidin-5-yl)-3aH-cyclopenta[d][1,2]oxazole-
4,6(5H,6aH)-dione (11). Triethylamine, 0.24 mL
(1.7 mmol), was added in one portion to a mixture of
0.17 g (0.8 mmol) of 4 and 0.30 g (1.6 mmol) of
N-benzylmaleimide in 4.00 mL of methanol. The
mixture was stirred for 5 h at room temperature, and
the precipitate was filtered off, washed with distilled
water, dried, and recrystallized from water. Yield
0.27 g (87%), white crystals, mp > 300°C (from
Me2CO–H2O). 1H NMR spectrum, δ, ppm: 1.82 s (3H,
CH3), 4.53 d and 4.58 d (1H each, CH2Ph, J =
14.9 Hz), 5.15 d and 5.63 d (1H, each, 4′-H, J =
9.4 Hz), 7.17 d (2H, o-H, J = 7.0 Hz), 7.27 t (1H, p-H,
J = 7.0 Hz), 7.30 t (2H, m-H, J = 7.0 Hz), 11.50 s (2H,
1-H, 3-H). 13C NMR spectrum, δC, ppm: 17.30 (CH3),
41.90 (CH2Ph), 56.50 (C3′), 79.90 (C4′), 98.10 (C5),
127.63 (Co), 127.84 (Cp), 128.66 (Cm), 135.60 (Ci),
149.80 (C7), 150.28 (C2), 154.30 (C6), 162.40 (C4),
171.30 (C5′), 173.20 (C2′). 15N NMR spectrum, δN,
ppm: 142.30 (N1), 156.39 (N3), 178.70 (N1′), 373.60
(N7′). Mass spectrum: m/z 353 (Irel 100%) [M – H]–.
Found, %: C 57.51; H 3.79; N 15.94. C17H14N4O5. Cal-
culated, %: C 57.63; H 3.98; N 15.81. M 354.32.
FUNDING
This study was performed in the framework of state
assignment of the Ministry of Science and Higher
Education of the Russian Federation (project
no. AAAA-A17-117011910025-6) and under financial
support by the Russian Foundation for Basic Research
(project no. 18-53-41004 Uzb_t).
CONFLICT OF INTERESTS
The authors declare the absence of conflict of
interests.
SUPPLEMENTARY INFORMATION
Supplementary information to this article is
available from the authors.
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