Synthesis of substituted 3,4-dihydropyrimidin-2(1H)-ones and pyrimidin-2(1H)-ones by the Biginelli reaction with 3,5-Di-tert-butyl-4- hydroxybenzaldehyde

Article abstract of DOI:10.1134/S1070428009100200

Three-component acid-catalyzed cyclocondensation of 3,5-di-tret-butyl-4- hydroxybenzaldehyde with urea and ethyl acetoacetate or α- nitroacetophenone (Biginelli reaction) under homogeneous conditions gave the corresponding 5-substituted 3,4-dihydropyrimid

Full text of DOI:10.1134/S1070428009100200

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 10, pp. 1535–1540. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © V.F. Sedova, V.P. Krivopalov, O.P. Shkurko, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 10,
pp. 1550–1555.
Synthesis of Substituted 3,4-Dihydropyrimidin-2(1H)-ones
and Pyrimidin-2(1H)-ones by the Biginelli Reaction
with 3,5-Di-tert-butyl-4-hydroxybenzaldehyde
V. F. Sedova, V. P. Krivopalov, and O. P. Shkurko
Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division, Russian Academy of Sciences,
pr. Akademika Lavrent’eva 9, Novosibirsk, 630090 Russia
e-mail: oshk@nioch.nsc.ru
Received November 25, 2008
Abstract—Three-component acid-catalyzed cyclocondensation of 3,5-di-tret-butyl-4-hydroxybenzaldehyde
with urea and ethyl acetoacetate or α-nitroacetophenone (Biginelli reaction) under homogeneous conditions
gave the corresponding 5-substituted 3,4-dihydropyrimidin-2(1H)-ones having in position 4 of the heteroring
an aryl substituent with sterically shielded hydroxy group. The condensation catalyzed by inorganic salts (Fe3+,
Co2+, Zn2+, Li+) was successful only with ethyl acetoacetate as initial methylene-active component. Under
analogous conditions, acetophenone and 4-fluoroacetophenone gave rise to 4,6-diarylpyrimidin-2(1H)-ones
which are capable of undergoing phenol–quinonemethide tautomerism.
DOI: 10.1134/S1070428009100200
3,4-Dihydropyrimidin-2(1H)-ones exhibit a broad
spectrum of biological activity, but the most interesting
is their ability to modulate calcium channels [1–3]. We
found that 4-aryl-5-nitro-6-phenyl-3,4-dihydropyrimi-
din-2(1H)-ones are low-toxic compounds and that they
exert an appreciable antiarrhythmic effect even at
a very low dose [4]. A usual technique in the design of
biologically active compounds with a broad spectrum
of biological activity is incorporation into a biological-
ly active molecule of one or several additional pharma-
cophoric groups with a different activity [5]. In this
connection, introduction into a 3,4-dihydropyrimidin-
2-one molecule of a phenol fragment having sterically
shielded hydroxy group could give rise to new prop-
erties, e.g., antiradical and antioxidant activity. Hetero-
cyclic compounds containing a 3,5-di-tert-butyl-4-hy-
droxyphenyl group have been reported to exhibit
antioxidant activity in combination with other kinds of
biological activity. Examples are calcium channel an-
tagonists of the 1,4-dihydropyridine [6] and thiazolidi-
none series [7], antisclerotic agents of the oxadiazole
series [8], and lipoprotein oxidation inhibitors of the
dihydropyrazole series [9]. Compounds possessing
antioxidant properties were found among 4-aryl-3,4-
dihydropyrimidin-2-one derivatives substituted at the
5-position with an alkoxycarbonyl group having both
simple and bulky alkyl radicals [10].
In the present work we tried to synthesize new
4-aryl-3,4-dihydropyrimidin-2(1H)-ones with a ster-
ically shielded hydroxy group in the aryl substituent.
For this purpose, we examined three-component cyclo-
condensation of 3,5-di(tert-butyl)-4-hydroxybenzalde-
hyde (I) with urea (IIa) or N-methylurea (IIb) and
various compounds having an activated methylene
group. As the latter, we used both traditional ethyl
acetoacetate and less reactive CH acids, α-nitroaceto-
phenone (III), acetophenone (IV), and 4-fluoroaceto-
phenone (V).
The reaction of ethyl acetoacetate with aldehyde I
and urea (IIa) under standard Biginelli conditions
(heating in boiling ethanol in the presence of a cata-
lytic amount of hydrochloric acid) gave ethyl 4-(3,5-di-
tert-butyl-4-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-
tetrahydropyrimidine-5-carboxylate (VIa) in 48%
yield (Scheme 1). The condensation in the presence of
inorganic salts, such as FeCl3·6H2O, CoCl2·6H2O,
and ZnCl2 (10 mol %) was characterized by appreci-
ably greater yield of compound VIa (77–88%) and
shorter reaction time. The yield of VIa reached 89%
when the reaction was carried out in acetonitrile using
LiBr as catalyst. The corresponding 1-methyl-substi-
tuted pyrimidine VIb was synthesized in high yield by
reaction of aldehyde I with ethyl acetoacetate and
1535

SEDOVA et al.
1536
Scheme 1.
O
Bu-t
t-Bu
HO
EtO
Me
N
O
O
O
HO
Catalyst
R
+
+
H2N
NHR
Me
OEt
HN
t-Bu
CHO
t-Bu
O
I
IIa, IIb
VIa, VIb
Ph
t-Bu
O2N
O
Catalyst
HO
NH
O
I
+
IIa
+
NO2
Ph
HN
t-Bu
III
t-Bu
HO
VII
C6H4R-4
t-Bu
C6H4R-4
O
Catalyst
Me
NH
O
HO
NH
O
I
+
IIa
+
[–2H]
HN
N
R
t-Bu
t-Bu
IV, V
VIII, IX
R = H (a), Me (b); VIII, R′ = H; IX, R′ = 4-F.
The structure of dihydropyrimidinones VIa, VIb,
and VII was confirmed by the analytical and spectral
data which were consistent with those reported for
other 5-alkoxycarbonyl- and 5-nitro-4-aryl-3,4-dihy-
dropyrimidin-2(1H)-ones. The mass spectra of VIa
and VIb contained all fragment ion peaks typical of
such compounds: [M]+, [M – C2H5]+, [M – COOC2H5]+,
[M – Ar]+, [M – Ar – C2H4]+, [M – C2H5OH]+, [M –
Ar – COOC2H5]+ [12]. Analogous fragmentation pat-
tern was observed for compound VII; it completely
coincided with the data reported for other 5-nitrodihy-
dropyrimidinones [4].
N-methylurea (IIb) in the presence of CoCl2·6H2O as
catalyst.
Under standard conditions (see above), aldehyde I
reacted with α-nitroacetophenone (III) and urea (IIa)
to give the expected condensation product, 4-(3,5-di-
tert-butyl-4-hydroxyphenyl)-5-nitro-6-phenyl-3,4-dihy-
dropyrimidin-2(1H)-one (VII) (Scheme 1). However,
the reaction occurred at a much lower rate; even after
heating for 24 h under reflux, the mixture contained
traces of initial aldehyde I, and the yield of compound
VII was 55%. Attempts to effect the condensation in
the presence of 10 mol % of CoCl2·6H2O were unsuc-
cessful: no cyclization product was detected after heat-
ing of the reaction mixture for 16 h under reflux. The
use of a larger amount of the catalyst was undesirable,
for it could favor side processes, including retro-Henry
reaction, which was observed by us previously [11].
In the condensations of aldehyde I with urea and
acetophenones IV and V having even less activated
methylene group than that in nitroacetophenone III,
instead of the expected diaryl-substituted 3,4-dihydro-
pyrimidin-2(1H)-one derivatives we isolated the corre-
Scheme 2.
OH
O
OH
t-Bu
Bu-t
t-Bu
Bu-t
t-Bu
Bu-t
N
HN
HN
O
N
H
C6H4R-4
O
N
C6H4R-4
O
N
C6H4R-4
H
A
B
A'
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

SYNTHESIS OF SUBSTITUTED 3,4-DIHYDROPYRIMIDIN-2(1H)-ONES
1537
D
sponding dehydrogenation products, 6-phenyl- and
1
6-(4-fluorophenyl)-4-(3,5-di-tert-butyl-4-hydroxy-
phenyl)pyrimidin-2(1H)-ones VIII and IX. Their
formation is consistent with the behavior of other
aromatic aldehydes in such reactions [13]. The con-
densation was difficult to occur, and unreacted alde-
hyde I was present in the reaction mixture even after
24 h. The use of a catalytic amount of FeCl3·6H2O or
CoCl2·6H2O had no appreciable effect on the reaction
course.
1.0
0.5
0.0
2
2
300 350
400
450 500
550
600 λ, nm
Compounds VIII and IX displayed in the IR spec-
tra an absorption band at 1630 cm–1 which is typical of
stretching vibrations of the carbonyl group in diaryl-
pyrimidin-2(1H)-ones but is not characteristic of the
corresponding dihydro derivatives [14]. The mass
spectra of VIII and IX contained strong molecular ion
peaks [M]+ (Irel ≥ 50%) and [M – 15]+ ion peaks
(Irel 100%), in keeping with published data for struc-
turally related compounds [15]; also, other fragment
ion peaks with intensities below 10% were present.
Fig. 1. Electronic absorption spectra of compound VIII in
(1) ethanol, c = 1×10–4 M, l = 0.5 cm, and (2) dimethyl sulf-
oxide, c = 0.55×10–4 M, l = 1.0 cm.
in solvent polarity, were observed previously for Schiff
bases having a 3,4-di-tert-butylphenol fragment [16].
Comparison of the intensities of the absorption bands
at λmax ~354 nm in the spectra of compounds VIII and
IX in ethanol and DMSO shows that the fraction of
tautomer B for compound IX (Fig. 2) is larger than
that for VIII (Fig. 1). This may be due to +M effect of
fluorine atom in the para position, which enhances
electron-donating effect of the 6-(4-fluorophenyl) sub-
stituent (as compared to 6-phenyl) on the neighboring
endocyclic nitrogen atom; increased basicity of the
latter stabilizes the corresponding tautomer B to
a greater extent.
1
The H NMR spectra of VIII and IX confirmed the
assumed structure.
Electronic absorption spectra could provide addi-
tional information on the structure of the isolated com-
pounds. In the UV spectra of 5-ethoxycarbonyl deriva-
tives VIa and VIb we observed a strong absorption
band in the region λ 280–290 nm, while the corre-
sponding band in the spectrum of 5-nitro derivative
VII was displaced by ~60 nm toward longer wave-
lengths, which is typical of 5-nitrodihydropyrimidin-2-
ones [4, 14].
Thus the behavior of 3,5-di-tert-butyl-4-hydroxy-
benzaldehyde in the Biginelli reaction is generally
similar to the behavior of other aromatic aldehydes,
and some specificity of reactions with participation of
aldehyde I may be attributed to its reduced reactivity.
First 3,4-dihydropyrimidin-2(1H)-one derivatives hav-
ing a 3,5-di-tert-butyl-4-hydroxyphenyl group in posi-
As shown previously [13, 14], the long-wave ab-
sorption band in the UV spectra of 4,6-diarylpyrim-
idin-2(1H)-ones is located in the region λ 340–360 nm
(logε 4.0–4.5). Analogous absorption band is observed
at λ 354 nm (logε 4.3) in the UV spectra of compounds
VIII and IX. However, unlike other diarylpyrimidi-
nones, the electronic absorption spectra of VIII and IX
in ethanol contain an absorption band in the visible
region (λ ~480 nm; logε 2.52 and 2.25, respectively).
This band may be attributed to structure B appearing
as a result of phenol–quinonemethide tautomerism
A↔B (Scheme 2).
D
2.0
1
1.5
1.0
0.5
0.0
2
2
In going from ethanol to strongly polar solvents
such as DMF and DMSO, the molar absorption coef-
ficient at the visible absorption maximum increases
approximately by an order of magnitude, indicating
that the above equilibrium is displaced toward
quinonemethide tautomer B (Figs. 1, 2). Analogous
variations in the spectral pattern, produced by increase
300
350
400
450
500
550
600 λ, nm
Fig. 2. Electronic absorption spectra of compound IX in
(1) ethanol, c = 1×10–4 M, l = 0.5 cm, and (2) dimethyl sulf-
oxide, c = 0.51×10–4 M, l = 1.0 cm.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

SEDOVA et al.
1538
tion 4 of the heteroring were synthesized. The use of
inorganic salts like Fe3+, Co2+, Zn2+, Li+ as catalysts
appreciably increases the yield of the cyclocondensa-
tion product obtained from ethyl acetoacetate rather
than from α-nitroacetophenone. The condensations
with acetophenone and 4-fluoroacetophenone lead to
the formation of only the corresponding oxidized
products, 4,6-diarylpyrimidin-2(1H)-ones, which give
rise to phenol–quinonemethide tautomeric equilibrium.
(Irel, %): 388 (38.3) [M]+, 373 (14.4) [M – Me]+, 359
(100) [M – Et]+, 331 (75.8) [M – t-Bu]+, 315 (57.2)
[M – COOEt]+, 183 (90.7) [M – C6H2(Bu-t)2OH]+, 155
(30.6), 137 (21.7) [M – Ar – EtOH]+, 110 (6.4) [M –
Ar – COOEt]+. Found, %: C 68.30; H 8.38; N 6.92.
[M]+ 388.2363 (HRMS). C22H32N2O4. Calculated, %:
C 68.01; H 8.30; N 7.21. M 388.2362.
b. A mixture of 1.56 g (12 mmol) of ethyl aceto-
acetate, 2.34 g (10 mmol) of aldehyde I, 1.20 g
(20 mmol) of urea, 30 ml of ethanol, and 0.28 g
(1 mmol) of iron(III) chloride hexahydrate was heated
for 4 h under reflux. After cooling, the precipitate was
filtered off and washed with ethanol. Yield 3.0 g
(77%), mp 247–248°C.
EXPERIMENTAL
The IR spectra were recorded in KBr on a Bruker
Vector 22 spectrometer. The electronic absorption
spectra in the UV and visible regions were measured
on a Specord M-40 spectrophotometer. The 1H and 13C
NMR spectra were obtained on Bruker AV-300 and
Bruker AM-400 instruments using DMSO-d6 as sol-
vent and reference (δ 2.50, δC 39.50 ppm). The mass
spectra (electron impact, 70 eV) were recorded on
a Finnigan MAT 8200 mass spectrometer with direct
sample admission into the ion source. The purity of the
isolated compounds was checked by TLC on Silufol
UV-254 plates using chloroform–ethanol (15:1) as
eluent.
c. A mixture of 1.56 g (12 mmol) of ethyl aceto-
acetate, 2.34 g (10 mmol) of aldehyde I, 1.20 g
(20 mmol) of urea, 30 ml of ethanol, and 0.24 g
(1 mmol) of cobalt(II) chloride hexahydrate was
heated for 5.5 h under reflux. Yield 3.1 g (80%),
mp 246.5–247.5°C.
d. A mixture of 0.78 g (6 mmol) of ethyl aceto-
acetate, 1.17 g (5 mmol) of aldehyde I, 0.60 g
(10 mmol) of urea, 15 ml of ethanol, and 0.10 g
(1 mmol) of zinc(II) chloride was heated for 20 h
under reflux. After cooling, the precipitate was filtered
off and washed with ethanol and water. Yield 1.70 g
(88%), mp 243–244°C (from EtOH).
Ethyl 4-(3,5-di-tert-butyl-4-hydroxyphenyl)-6-
methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
boxylate (VIa). a. A mixture of 1.56 g (12 mmol) of
ethyl acetoacetate, 2.34 g (10 mmol) of aldehyde I,
1.20 g (20 mmol) of urea, 20 ml of ethanol, and 1.5 ml
of concentrated hydrochloric acid was heated for 8.5 h
under reflux. Additional portions of urea, 0.50 g
(8 mmol), and concentrated hydrochloric acid, 0.3 ml,
were added, and the mixture was heated for 8.5 h more
under reflux. After cooling, the precipitate was filtered
off and washed in succession with ethanol, a saturated
solution of NaHCO3, water, and ethanol again. Yield
1.67 g (48%), mp 247–248°C (from EtOH). UV spec-
trum (EtOH), λmax, nm (logε): 206 (4.41), 283 (4.04).
IR spectrum, ν, cm–1: 3612 (OH); 3238, 3110 (NH);
2955 (C–H in t-Bu); 1711, 1696 (C=O); 1227 (C–O).
1H NMR spectrum (400 MHz), δ, ppm: 1.13 t (3H,
e. Lithium bromide, 50 mg (0.57 mmol), was added
to a mixture of reactants prepared as described above
in d in 5 ml of acetonitrile, and the mixture was heated
for 10 h under reflux. The mixture was cooled, and the
precipitate was filtered off and washed with ethanol
and water. Yield 1.73 g (88%).
Ethyl 4-(3,5-di-tert-butyl-4-hydroxyphenyl)-1,6-
dimethyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-car-
boxylate (VIb). A mixture of 0.78 g (6 mmol) of ethyl
acetoacetate, 1.17 g (5 mmol) of aldehyde I, 0.74 g
(10 mmol) of N-methylurea (IIb), 15 ml of ethanol,
and 0.12 g (0.5 mmol) of cobalt(II) chloride hexahy-
drate was heated for 6 h under reflux. After cooling,
the precipitate was filtered off and washed with etha-
nol and water. Yield 1.55 g (77%), mp 190–191°C
(from EtOH). UV spectrum (EtOH), λmax, nm (logε):
204 (4.52), 285 (3.99). IR spectrum, ν, cm–1: 3605
(OH), 3381 (NH), 2965 (C–H in t-Bu), 1705 and 1680
3
CH3CH2, J = 7.2 Hz), 1.35 s (18H, t-Bu), 2.21 s (3H,
3
6-Me), 4.01 q (2H, CH2O, J = 7.2 Hz), 5.05 d (1H,
4-H, 3J = 3.2 Hz), 6.82 s (1H, OH), 7.04 s (2H, Harom),
7.55 br.s (1H, 3-H), 9.06 s (1H, 1-H). 13C NMR spec-
trum (100 MHz), δC, ppm: 14.18 (CH3CH2), 17.67
(6-CH3), 30.29 [(CH3)3C], 34.43 [(CH3)3C)], 53.92
(C4), 59.14 (CH2O), 100.14 (C5), 122.31 (C9, C11),
136.18 (C7), 138.89 (C8, C12), 147.59 (C6), 152.52 and
152.94 (C2, C10), 165.53 (5-CO). Mass spectrum, m/z
1
(C=O), 1611, 1240 (C–O). H NMR spectrum
(400 MHz), δ, ppm: 1.16 t (3H, CH3CH2, 3J = 7.0 Hz),
1.34 s (18H, t-Bu), 2.43 s (3H, 6-CH3), 3.11 s (3H,
3
1-CH3), 4.05 q (2H, CH2O, J = 7.0 Hz), 5.05 d (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

SYNTHESIS OF SUBSTITUTED 3,4-DIHYDROPYRIMIDIN-2(1H)-ONES
1539
4-H, 3J = 3.6 Hz), 6.86 s (1H, OH), 6.99 s (2H, Harom),
7.78 d (1H, 3-H). 13C NMR spectrum (100 MHz), δC,
ppm: 14.19 (CH3), 16.01 (6-CH3), 29.63 (1-CH3),
30.32 [(CH3)3C], 34.54 [(CH3)3C], 52.46 (C4), 59.58
(CH2O), 103.95 (C5), 122.06 (C9, C11), 135.42 (C7),
139.07 (C8, C12), 149.60 (C6), 153.05 and 153.70 (C2,
C10), 165.82 (5-CO). Mass spectrum, m/z (Irel, %): 402
(31.5) [M]+, 387 (15.9) [M – Me]+, 373 (85.1) [M –
Et]+, 345 (23.3) [M – Bu]+, 329 (51.4) [M – COOEt]+,
197 (100) [M – Ar]+, 169 (26.8), 151 (28.5) [M – Ar –
EtOH]+, 124 (9.4) [M – Ar – COOEt]+. Found, %:
C 68.96; H 8.66; N 6.83. [M]+ 402.2524 (HRMS).
C23H34N2O4. Calculated, %: C 68.63; H 8.51; N 6.96.
M 402.2518.
C15, C16, C17, C18); 133.12 (C7); 139.36 (C8, C12);
149.14 (C6); 150.48 (C10); 153.64 (C2). Mass spectrum,
m/z (Irel, %): 423 (22.4) [M]+, 406 (100) [M – OH]+,
378 (17.0) [M – OH – CO]+, 377 (62.6) [M – NO2]+,
376 (7.2) [M – HNO2]+, 361 (31.6), 334 (24.9), 292
(17.3), 218 (39.6) [M – Ar]+, 171 (22.6) [M – Ar –
HNO2]+, 104 (12.9) [PhC=NH]+, 77 (6.1) [Ph]+.
Found, %: C 67.29; H 6.90; N 9.38. [M]+ 423.2148
(HRMS). C24H29N3O4 ·0.5C2H5OH. Calculated, %:
C 67.24; H 7.22; N 9.41. M 423.2158.
4-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-phenyl-
pyrimidin-2(1H)-one (VIII). A mixture of 0.72 g
(6 mmol) of acetophenone, 1.2 g (5 mmol) of aldehyde
I, 0.6 g (10 mmol) of urea, 10 ml of ethanol, and
0.8 ml of concentrated hydrochloric acid was heated
for 13 h under reflux. Additional portions of urea, 0.2 g
(3.3 mmol), and concentrated hydrochloric acid,
0.2 ml, were added, and the mixture was heated for
10 h more under reflux. The mixture was cooled to
room temperature, and the precipitate was filtered off
and washed in succession with ethanol, a saturated
aqueous solution of sodium hydrogen carbonate, water,
and ethanol again. Yield 0.6 g (32%), mp 355–356°C
(from EtOH). Electronic absorption spectrum, λmax, nm
(logε): in EtOH: 203 (4.63), 251 (4.13), 354 (4.32),
483 (2.52); in DMSO: 354 (4.08), 490 (3.58). IR spec-
trum, ν, cm–1: 3628 (OH), 3282, 3186 (NH), 2951
4-(3,5-Di-tert-butyl-4-hydroxyphenyl)-5-nitro-
6-phenyl-3,4-dihydropyrimidin-2(1H)-one (VII).
A mixture of 1.98 g (12 mmol) of nitroacetophenone
(III), 2.34 g (10 mmol) of aldehyde I, 1.20 g
(20 mmol) of urea, and 26 ml of ethanol was stirred,
1.5 ml of concentrated hydrochloric acid was added,
and the mixture was heated for 5 h under reflux. A 0.6-
g (10-mmol) portion of urea was added, the mixture
was heated for 5 h under reflux, 0.3 g (5 mmol) of urea
and 0.5 ml of concentrated hydrochloric acid in 8 ml of
ethanol were added, the mixture was heated under
reflux, and the last portion of urea (0.3 g) and 6 ml of
ethanol were added in 19 h after the mixture began to
boil. The progress of the reaction was monitored by
TLC. When the initial aldehyde disappeared (overall
reaction time 24 h), the yellow–orange transparent
mixture was cooled to room temperature and was left
to stand for several hours. The precipitate was filtered
off, washed with a small amount of 90% ethanol,
water, and ethanol again, and dried on a filter. Yield
2.2 g. The filtrate was kept in a refrigerator to isolate
an additional portion (0.15 g) of compound VII. Over-
all yield 2.35 g (55%), mp 243–244°C (from EtOH).
UV spectrum (EtOH), λmax, nm (logε): 206 (4.64), 236
(4.15), 348 (3.74). IR spectrum, ν, cm–1: 3630 (OH),
3370, 3215 (NH), 2959 (C–H in t-Bu), 1701 (C=O),
1
(C–H in t-Bu), 1628 (C=O), 1231 (C−O). H NMR
spectrum (400 MHz), δ, ppm: 1.45 s (18H, t-Bu),
7.24 s (1H, 5-H), 7.51–7.64 m (4H, Harom, OH), 7.74 s
3
(2H, Harom), 8.11 d (2H, Harom, J = 6.8 Hz), 11.59 br.s
(1H, NH). Mass spectrum, m/z (Irel, %): 376 (50.5)
[M]+, 361 (100) [M – Me]+, 345 (5.6) [M – 31]+, 104
(5.8) [PhC=NH]+, 77 (4.2) [Ph]+. Found, %: C 76.32;
H 7.40; N 7.28. [M]+ 376.2148 (HRMS). C24H28N2O2.
Calculated, %: C 76.56; H 7.50; N 7.44. M 376.2151.
4-(3,5-Di-tert-butyl-4-hydroxyphenyl)-6-(4-
fluorophenyl)pyrimidin-2(1H)-one (IX) was synthe-
sized in a similar way. Yield 0.63 g (32%), mp 355–
356.5°C (from EtOH). Electronic absorption spectrum,
λmax, nm (logε): in EtOH: 203 (4.63), 252 (4.01), 354
1
1628, 1499 and 1321 (NO2), 1246. H NMR spectrum
(4.31), 479 (2.20); in DMSO: 356 (4.19), 488 (3.67).
IR spectrum, ν, cm–1: 3629 (OH), 3402, 3279 (NH),
2955 (C–H in t-Bu), 1630 (C=O), 1231 (C−O).
1H NMR spectrum (300 MHz), δ, ppm: 1.47 s (18H,
t-Bu), 7.27 s (1H, 5-H), 7.36 d.d (2H, Harom, 3JHF = 8.6,
3JHH = 8.4 Hz), 7.55 s (OH), 7.71 s (2H, Harom),
3
(400 MHz), δ, ppm: 1.07 t (1.5H, CH3CH2OH, J =
7.0 Hz), 1.42 s (18H, t-Bu), 3.45 q (1H, CH3CH2OH,
3J = 7.0 Hz), 5.55 d (1H, 4-H, 3J = 3.7 Hz), 6.99 s (1H,
OH), 7.21 s (2H, Harom), 7.38 m (2H, Harom), 7.50 m
(3H, Harom), 8.22 br.s (1H, 3-H), 10.0 s (1H, 1-H).
13C NMR spectrum (100 MHz), δC, ppm: 18.41
(CH3CH2OH); 30.23 [(CH3)3C]; 34.46 [(CH3)3C];
54.24 (C4); 56.00 (CH3CH2OH); 122.30 (C5); 122.43
(C9, C11); 127.46, 128.45, 129.77, 132.61 (C13, C14,
3
4
8.23 d.d (2H, Harom, JHH = 8.0, JHF = 5.6 Hz), 12.0 s
(1H, NH). Mass spectrum, m/z (Irel, %): 394 (47.4)
[M]+, 379 (100) [M – Me]+, 363 (5.8) [M – 31]+, 122
(8.9) [FC6H4C=NH]+, 95 (3.3) [FC6H4]+. Found, %:
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 10 2009

SEDOVA et al.
1540
C 72.87; H 6.81; F 5.00; N 7.11. [M]+ 394.2052
(HRMS). C24H27FN2O2. Calculated, %: C 73.07;
H 6.90; F 4.82; N 7.10. M 394.2056.
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pp. 2715; ibid., p. 2719.
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ev, V.M., and Allakhverdiev, M.A., Zh. Prikl. Khim.,
2006, vol. 79, p. 796.
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