Heterocyclization of functionalized heterocumulenes with C,N-, C,O-, and C,S-binucleophiles: X. 1-Chloroalkyl isocyanates in the synthesis of new 5-aroyldihydropyrimidines

Article abstract of DOI:10.1134/S1070428009050182

Reactions of 1-chlorobenzyl isocyanates with N,S-aroylketene acetals depending on the conditions provide either 5-aroyl-6-methylsulfanyl-3,4- dihyropyrimidin-2(1H)-ones or 5-aroyldihyropyrimidine-2,4(1H,3H)-diones. 1-Aryl-2,2,2-trifluoro-1-chloroethyl iso

Full text of DOI:10.1134/S1070428009050182

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2009, Vol. 45, No. 5, pp. 755−761. © Pleiades Publishing, Ltd., 2009.
Original Russian Text © O.V. Kushnir, V.A. Sukach, M.V. Vovk, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 5, pp. 768−774.
Heterocyclization of Functionalized Heterocumulenes
with C,N- , C,O-, and C,S-Binucleophiles: X.
1-Chloroalkyl Isocyanates in the Synthesis of New
5-Aroyldihydropyrimidines
O. V. Kushnira, V. A. Sukachb, and M. V. Vovkb
aFed’kovich Chernovitsy National University,
bInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, 02094 Ukraine
e-mail: mvovk@i.com.ua
Received March 14, 2008
Abstract—Reactions of 1-chlorobenzyl isocyanates with N,S-aroylketene acetals depending on the conditions
provide either 5-aroyl-6-methylsulfanyl-3,4-dihyropyrimidin-2(1H)-ones or 5-aroyldihyropyrimidine-2,4(1H,3H)-
diones. 1-Aryl-2,2,2-trifluoro-1-chloroethyl isocyanates in a similar condensation gave 5-aroyl-6-methylsulfanyl-
2-trifluoromethyl-2,3-dihyropyrimidin-4(1H)-ones.
DOI: 10.1134/S1070428009050182
5-Acyl-3,4-dihyropyrimidin-4(1H)-one are far less
understood than their 5-alkoxycarbonyl-substituted
analogs [2, 3], although Kolosov et al. [4] regard them
as promising synthons for the preparation of pharmaco-
logically important compounds. In the classical version
of their synthesis by Biginelli three-component con-
densation from aldehydes, urea, and β-diketones only
acetylacetone [4–7] and benzoylacetone [6–8] were used.
Inasmuch as the pharmacological properties of
dihyropyrimidin-2-one systems are governed alongside
their heterocyclic scaffold also by the degree of the
functionalization [9–11] especially important are their
polyfunctional derivatives [2]. However in the series of
5-acyldihyropyrimidin-2-ones a deeper functionalization
is restricted by the acylation in the position 3 of the
heterocycle [4].
polyfunctional dihyropyrimidines. To this end in the present
study reactions were investigated between 1-chloro-
alkylisocyanates with available N,S-aroylketene acetals
that were widely applied to the preparation of various
types of heterocyclic compounds [15–18].
It was established that 1-chlorobenzyl isocyanates Ia–
Id reacted with N,S-ketene acetals IIa–IIe in anhydrous
toluene at room temperature providing 5-aroyl-6-
methylsulfanyl-3,4-dihyropyrimidin-2(1H)-ones IIIa–IIIh
in 48–65% yields. In reaction in the moist toluene (the
solvent not distilled over P2O5 or specially prepared by
adding 2 equiv of water) 5-aroyldihyropyrimidine-
2,4(1H,3H)-diones IVa–IVh were obtained, the
representatives of materially unknown 5-aroyl-5,6-
dihyrouracyls [19] (Scheme 1).
It was seemingly logical to assume that the formation
of compounds of IV type was due to the hydrolysis of
preliminary formed compounds III under the reaction
conditions. However independent experiments showed
that reagents IIIa and IIIb were stable against hydrolysis
in neutral, acid and alkaline media, and their MeS group
was not prone to the nucleophilic substitution. Therefore
we assumed the following scheme of reagents I and II
cyclocondensation. The process starts by the addition of
the nucleophilic β-carbon from the enamine fragment of
We formerly [12, 13] developed a procedure for the
dihyropyrimidine ring formation alternative to Biginelli
reaction consisting in the condensation of 1-chlorobenzyl
isocyanates with deactivated enamines. This approach
proved to be also efficient in the synthesis of 6-methyl-
sulfanyl-5-nitropyrimidines using as nucleophiles N,S-
nitroketene acetals [14].
It was purposeful to extend the synthetic opportunities
of the procedure to the preparation of other types of
755

KUSHNIR et al.
756
Scheme 1.
Ar1
N
O
Ar1
N C O
O
Ar1
NH
Cl
Cl
Ia_Id
Ar2
MeS
H2O
a
_HCl
+
N
O
O
O
Ar1
O
Ar3
IIIa_IIIh
Ar2
MeS
Ar2
MeS
N
Cl
H
O
O
Ar1
NH
NH
Ar3
IIa_IId
N
Ar3
O
Ar1
O
b
H2O
_MeSH
Ar2
Ar2
N
Cl
A
H
_HCl
N
O
HO
N
Ar3
Ar3
B
IVa_IVh
I,Ar1 = 2-FC6H4 (a), 3-BrC6H4 (b), 4-NO2C6H4 (c), 3,4-Cl2C6H3 (d); II,Ar2 = 4-ClC6H4,Ar3 = Ph (a), 4-ClC6H4 (b), 4-PhOC6H4
(c);Ar2 = 4-BrC6H4,Ar3 = Ph (d);Ar2 = 4-MeC6H4,Ar3 = 3,4-Me2C6H3 (e); III, IV,Ar1 = 4-NO2C6H4,Ar2 = 4-ClC6H4,Ar3 = Ph
(a), 4-ClC6H4 (b), 4-PhOC6H4 (c);Ar1 = 3-BrC6H4,Ar2 =Ar3 = 4-ClC6H4 (d);Ar2 = 4-BrC6H4,Ar3 = Ph,Ar1 = 3-BrC6H4 (e),
4-NO2C6H4 (f), 3,4-Cl2C6H3 (g);Ar1 = 2-FC6H4,Ar2 = 4-MeC6H4,Ar3 = 3,4-Me2C6H3 (h).
constants of 3.3–4.2 Hz, and also the singlet of protons
of MeS group at 1.68–1.78 ppm. The signals of atoms
C4 in the 13C NMR spectra were observed in the region
50–54 ppm characteristic of analogous 5,6-bifunctional
dihyropyrimidin-2-ones [14].
N,S-benzoylketene acetal II to the activated C=N bond
of N-chloroformylimine form [20] of 1-chlorobenzyl iso-
cyanate (I) along the diazadiene mechanism [21] leading
to the formation of intermediate A that undergoes
cyclization into target compound III (Scheme 1, path a).
In the presence in the reaction mixture of moisture and
HCl traces the nitrogen atom of the imino group of
intermediate A suffers a protonation that favors an easy
substitution of a methylmercapto for a hydroxy group to
form intermediate B which likewise converts into
compound IV (path b).
In the IR spectra of pyrimidin-2,4-diones IVa–IVh
the endocyclic C=O groups give rise to a single strong
band in the range 1660–1680 cm–1, and the bands of the
exocyclic C=O group are shifted to the region 1720–
1735 cm–1 due to the lack of conjugation with the C=C
bond.
1
In the H NMR spectra of compounds IVa–IVg
The homogeneity and the composition of compounds
IIIa–IIIh and IVa–IVh were confirmed by the data of
HPLC-MS and elemental analysis, and the structure, by
IR, 1H and 13C NMR spectra. Mass spectra of all com-
pounds contain strong peaks of molecular ions and weak
peaks of fragment ions indicating the stability of the
corresponding molecules.
attention is attracted by the presence of a spin system
AΒ with the coupling constant 6.9–7.6 Hz where the
upfield signal (5.13–5.32 ppm) corresponds to the proton
H6, and the downfield signal (5.53–5.64 ppm), to the
proton H5.
The analysis of spatial models showed that at the
axial position of these protons the torsion angle H5CCH6
was ∼170° and therefore according to the Karplus–
Conroy equation [22] it should correspond to the coupling
constant >10 Hz. Hence we suggested that the protons
take the equatorial-axial position with the torsional angle
∼70° and the coupling constant 6.5–7.5 Hz.
The IR spectra of pyrimidin-2-ones IIIa–IIIh con-
tained absorption bands in the region 1640–1655 cm–1
which could be reliably assigned to the C=O group of the
ureide fragment, and the bands at 1685–1705 cm–1, to
the C=O group of the exocyclic aroyl substituent. In the
1H NMR spectra of these compounds the most
characteristic signals are the doublets of protons H4
(5.15–5.38) and NH (8.03–8.59 ppm) with coupling
In the case of compound IVg containing in the position
6 a 2-fluorophenyl substituent the signals of protons H5
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HETEROCYCLIZATION OF FUNCTIONALIZED HETEROCUMULENES..: X
757
and H6 are superimposed and appear as a broadened
singlet at 5.23 ppm.
72.4–73.5 ppm indicate the presence in the structure of
the molecule of an aminal fragment N–C(CF3)Ar1–NH
[23, 24]. In the 13C NMR spectrum the signals of C2
atoms appeared at 75–80 ppm as a quartet with the
coupling constant 2JC–F 28–29 Hz.
Aiming at the synthesis of trifluoromethyl-containing
pyrimidinones, promising bioactive substances, we
involved into the condensation with N,S-thioketene acetals
IIc–IIf 1-aryl-2,2,2-trifluoro-1-chloroethyl isocyanates
Va–Vc. It was found that they reacted in dry benzene at
room temperature only in the presence of an organic base
(triethylamine) and formed in 56–73% yield not 5-aroyl-
6-methylsulfanyl-4-trifluoromethyl-3,4-dihydropyrimidin-
2(1H)-ones VI, but their structural isomers, 5-aroyl-6-
methylsulfanyl-2-trifluoromethyl-2,3-dihydropyrimidin-
4(1H)-ones VIIa–VIId (Scheme 2). This course of the
process is evidently due to the primary formation under
the action of the base of an anion of the ketene acetal on
whose β-carbon atom is directed the attack of the iso-
cyanate group. As a consequence an N-alkylidene-carb-
amoyl intermediate C forms that then undergoes cycliza-
tion into compound VIIa–VIId.
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
1
UR-20 from samples pelletized with KBr. H and
19F NMR spectra from solutions in DMSO-d6 were
registered on a spectrometer Varian-Gemini (299.94 and
188.14 MHz respectively), internal references TMC (1H)
and CCl3F (19F). 13C NMR spectra in DMSO-d6 were
registered on a spectrometer Bruker Arano DRX-500
(125.75 MHz), internal reference TMS. Chromatomass
spectra were measured on an instrument PE SCIEX API
150 EX [detectors UV (254 nm) and ELSD].
1-Chlorobenzyl isocyanates Ia–Id and 1-aryl-2,2,2-
trifluoro-1-chloroethyl isocyanates Va–Vc were obtained
by procedures [13] and [25] respectively.
Asimilar trend was formerly observed in the reaction
of isocycnates of V type with N-substituted amino-
crotonates [23].
5-Aroyl-1,4-diaryl-6-methylsulfanyl-3,4-dihyro-
pyrimidine-2(1H)-ones IIIa–IIIh and 5-aroyl-3,6-
diaryl-2,4(1H,3H)-diones IVa–IVh. To a solution of
2.8 mmol of S,N-ketene acetal IIa–IIe in 20 ml of
anhydrous (for compounds IIIa–IIIh) or containing
0.1 ml of water (for compounds IVa–IVh) toluene was
added 2.8 mmol of isocyanate Ia–Id, and the mixture
was left standing at room temperature for 24 h. Then to
The structure of compounds VIIa–VIId was
confirmed by physicochemical methods. In the IR spectra
of the substances the absorption bands of the C=O groups
appeared as broadened bands at 1650–1680 cm–1, and
those of NH groups, at 3250–3260 cm–1. These data and
also the 19F NMR spectra that contain the signals of the
fluorine atoms belonging to the trifluoromethyl groups at
Scheme 2.
1
O
Ar
CF3
NH
Ar2
O
MeS
O
N
Ar3
O
CF3
Ar2
Et3N
Ar1
N C O
+
VI
MeS
IIc_IIf
NH
Ar3
Cl
O
O
N
O
Ar1
Va_Vc
Ar2
NH
Ar1
CF3
Ar2
MeS
N
CF3
_HCl
MeS
NH
Ar3
VIIa_VIId
Ar3
C
II,Ar2 = 4-ClC6H4,Ar3 = 4-FC6H4 (f); V,Ar1 = 4-FC6H4 (a), 4-MeC6H4 (b), 4-MeOC6H4 (c); VII,Ar1 =Ar3 = 4-FC6H4,Ar2 =
4-ClC6H4 (a);Ar1 = 4-MeC6H4,Ar2 = 4-BrC6H4,Ar3 = Ph (b);Ar1 = 4-MeC6H4,Ar2 = 4-ClC6H4,Ar3 = 4-PhOC6H4 (c);Ar1 =
4-MeOC6H4,Ar2 = 4-MeC6H4,Ar3 = 3,4-Me2C6H3 (d).
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KUSHNIR et al.
758
5.16 d (1H, H4, J 3.6 Hz), 7.24–7.83 m (10Harom), 8.03 d
(2Harom), 8.46 d (1H, NH, J 3.6 Hz). 13C NMR spectrum,
δ, ppm: 17.54 (CH3S), 54.18 (C4), 119.51 (C5), 121.18,
121.78, 125.26, 128.12, 128.65, 130.89, 131.51, 132.13,
136.15, 137.05, 137.57, 141.00, 144.66 (Carom), 152.08
(C6), 192.29 (Ar2C=O). Found, %: N 5.26; S 6.03. M+ 549.
C24H17BrCl2N2O2S. Calculated, %: N 5.11; S 5.85.
M 548.8.
the reaction mixture 20 ml of hexane was added, the
precipitate was filtered off, dried, and crystallized from
ethanol.
6-Methylsulfanyl-4-(4-nitrophenyl)-1-phenyl-5-
(4-chlorobenzoyl)-3,4-dihyropyrimidin-2(1H)-one
(IIIa). Yield 63%, mp 211–213°C. IR spectrum, cm–1:
1
3220 (NH), 1690 (C=O), 1640 (C=O). H NMR spec-
trum, δ, ppm: 1.78 s (3H, CH3S), 5.30 d (1H, H4, J 3.9 Hz),
7.28–7.49 m (6Harom), 7.67–7.84 m (5Harom), 8.27 d
(2Harom), 8.53 d (1H, NH, J 3.9 Hz). 13C NMR spectrum,
δ, ppm: 17.63 (CH3S), 51.87 (C4), 118.22 (C5), 123.77,
127.59, 128.05, 128.92, 129.78, 130.46, 134.38, 135.33,
137.17, 139.13, 143.14, 149.55 (Carom), 152.11 (C6), 152.34
(C2), 192.32 (Ar2C=O). Found, %: N 8.66; S 6.72.
M+ 480. C24H18ClN3O4S. Calculated, %: N 8.76; S 6.68.
M 480.0.
5-(4-Bromobenzoyl)-4-(3-bromophenyl)-6-
methylsulfanyl-1-phenyl-3,4-dihydropyrimidin-
2(1H)-one (IIIe). Yield 65%, mp 184–186°C. IR
spectrum, cm–1: 3220 (NH), 1695 (C=O), 1655 (C=O).
1H NMR spectrum, δ, ppm: 1.69 s (3H, CH3S), 5.15 d
(1H, H4, J 4.2 Hz), 7.19–7.56 m (9Harom), 7.66 d (2Harom),
7.72 d (2Harom), 8.45 d (1H, NH, J 4.2 Hz). 13C NMR
spectrum, δ, ppm: 17.55 (CH3S), 54.04 (C4), 118.99 (C5),
121.78, 125.23, 126.55, 127.62, 128.11, 129.22, 129.71,
130.57, 130.89, 131.58, 137.28, 137.62, 142.20, 144.88
(Carom), 152.31 (C6), 155.73 (C2=O), 192.59 (Ar2C=O)
Found, %: N 4.86; S 5.89. M+ 559. C24H18Br2N2O2S.
Calculated, %: N 5.02; S 5.74. M 558.3.
6-Methylsulfanyl-4-(4-nitrophenyl)-5-(4-chloro-
benzoyl)-1-(4-chlorophenyl)-3,4-dihyropyrimidin-
2(1H)-one (IIIb). Yield 61%, mp 249–250°C. IR
spectrum, cm–1: 3215 (NH), 1685 (C=O), 1645 (C=O).
1H NMR spectrum, δ, ppm: 1.72 s (3H, CH3S), 5.31 d
(1H, H4, J 3.9 Hz), 7.28–7.49 m (6Harom), 7.66 d (2Harom),
7.82 d (2Harom), 8.23 d (2Harom), 8.58 d (1H, NH,
J 3.9 Hz). 13C NMR spectrum, δ, ppm: 17.64 (CH3S),
54.16 (C4), 118.73 (C5), 123.87, 127.64, 128.06, 128.60,
130.51, 131.58, 132.16, 136.05, 137.10, 137.61, 142.18,
146.94 (Carom), 149.34 (C6), 151.96 (C2), 191.41
(Ar2C=O). Found, %: N 7.98; S 6.46. M+ 514.
C24H17Cl2N3O4S. Calculated, %: N 8.17; S 6.23. M 514.3.
5-(4-Bromobenzoyl)-6-methylsulfanyl-4-(4-nitro-
phenyl)-1-phenyl-3,4-dihydropyrimidin-2(1H)-one
(IIIf). Yield 63%, mp 194–196°C. IR spectrum, cm–1:
1
3225 (NH), 1705 (C=O), 1650 (C=O). H NMR spec-
trum, δ, ppm: 1.69 s (3H, CH3S), 5.28 d (1H, H4, J 3.9 Hz),
7.24–7.89 m (11Harom), 8.40 d (2Harom), 8.59 d (1H, NH,
J 3.9 Hz). 13C NMR spectrum, δ, ppm: 17.64 (CH3S),
54.08 (C4), 118.18 (C5), 123.85, 126.45, 127.58, 128.04,
128.59, 129.76, 130.56, 131.51, 137.17, 137.66, 143.25,
146.94 (Carom), 149.54 (C6), 152.10 (C2=O), 192.50
(Ar2C=O). Found, %: N 8.17; S 5.87. [M + 1]+ 525.
C24H18BrN3O4S. Calculated, %: N 8.01; S 6.11. M 524.4.
6-Methylsulfanyl-4-(4-nitrophenyl)-5-(4-chloro-
benzoyl)-1-(4-phenoxyphenyl)-3,4-dihydropyr-
imidin-2(1H)-one (IIIc). Yield 57%, mp 168–170°C.
IR spectrum, cm–1: 3225 (NH), 1705 (C=O), 1650 (C=O).
1H NMR spectrum, δ, ppm: 1.73 s (3H, CH3S), 5.29 d
(1H, H4, J 4.0 Hz), 6.96–7.52 m (11Harom), 7.69 d
(2Harom), 7.81 d (2Harom), 8.23 d (2Harom), 8.57 d (1H,
NH, J 4.0 Hz). 13C NMR spectrum, δ, ppm: 17.68
(CH3S), 54.11 (C4), 117.50 (C5), 118.04, 119.11, 123.93,
127.63, 128.26,128.63, 128.87, 130.11, 131.43, 132.12,
133.32, 135.01, 137.42, 143.34, 146.96, 149.57 (Carom),
152.25 (C6), 156.10 (C2=O), 192.43 (Ar2C=O). Found,
%: N 7.29; S 5.39. M+ 572. C30H22ClN3O5S. Calculated,
%: N 7.35; S 5.61. M 572.0.
5-(4-Bromobenzoyl)-4-(3,4-dichlorophenyl)-6-
methylsulfanyl-1-phenyl-3,4-dihyropyrimidin-
2(1H)-one (IIIg). Yield 58%, mp 241–242°C. IR
spectrum, cm–1: 3235 (NH), 1690 (C=O), 1655 (C=O).
1H NMR spectrum, δ, ppm: 1.68 s (3H, CH3S), 5.16 d
(1H, H4, J 4.2 Hz), 7.20–7.38 m (6Harom), 7.59–7.73 m
(6Harom), 8.47 d (1H, NH, J 3.9 Hz). 13C NMR spectrum,
δ, ppm: 17.59 (CH3S), 53.58 (C4), 118.23 (C5), 126.56,
127.68, 128.15, 128.56, 130.29, 130.68, 130.94, 131.12,
131.60, 132.85, 137.22, 137.59, 142.63, 143.31 (Carom),
150.28 (C6), 152.21 (C2), 192.58 (Ar2C=O). Found, %:
N 5.25; S 6.07. [M + 1]+ 549. C24H17BrCl2N2O2S.
Calculated, %: N 5.11; S 5.85. M 548.3.
4-(3-Bromophenyl)-6-methylsulfanyl-5-(4-
chlorobenzoyl)-1-(4-chlorophenyl)-3,4-dihydro-
pyrimidin-2(1H)-one (IIId). Yield 59%, mp 177–
179°C. IR spectrum, cm–1: 3215 (NH), 1700 (C=O), 1655
1-(3,4-Dimethylphenyl)-5-(4-methylbenzoyl)-6-
methylsulfanyl-4-(2-fluorophenyl)-3,4-dihyro-
1
(C=O). H NMR spectrum, δ, ppm: 1.72 s (3H, CH3),
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HETEROCYCLIZATION OF FUNCTIONALIZED HETEROCUMULENES..: X
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pyrimidine-2(1H)-one (IIIh). Yield 48%, mp 195–
197°C. IR spectrum, cm–1: 3230 (NH), 1700 (C=O), 1640
(C=O). 1H NMR spectrum, δ, ppm: 1.73 s (3H, CH3S),
5.38 d (1H, H4, J 3.3 Hz), 7.03–7.34 m (9Harom), 7.60 d
(2Harom), 8.03 d (1H, NH, J 3.3 Hz). 13C NMR spectrum,
δ, ppm: 17.91 (CH3S), 18.91, 19.27, 21.06 (3CH3), 50.69
(C4), 119.52 (C5), 124.81, 127.11, 128.10, 128.60, 128.81,
128.97, 129.15, 129.92, 129.97, 130.68, 135.14, 135.19,
135.54, 135.85, 137.56, 143.38 (Carom), 152.37 (C6),
160.36 (C2), 192.56 (Ar2C=O). Found, %: N 6.11; S 7.09.
[M + 1]+ 461. C27H25FN2O2S. Calculated, %: N 6.08;
S 6.96. M 460.6.
C 56.79; H 3.15; N 8.85. M+ 484. C23H15Cl2N3O5.
Calculated, %: C 57.04; H 3.12; N 8.68. M 484.3.
6-(4-Nitrophenyl)-3-(4-phenoxyphenyl)-5-(4-
chlorobenzoyl)dihyropyrimidine-2,4(1H,3H)-dione
(IVd). Yield 45%, mp 228–230°C. IR spectrum, cm–1:
1
3270 (NH), 1735 (C=O), 1680 (C=O). H NMR
spectrum, δ, ppm: 5.31 d (1H, H6, J 6.9 Hz), 5.57 d (1H,
H5, J 6.9 Hz), 7.01–7.15 m (7Harom), 7.38 d (2Harom),
7.54 d (2Harom), 7.79 d (2Harom), 8.04 d (2Harom), 8.23 d
(2Harom), 8.66 s (1H, NH). 13C NMR spectrum, δ, ppm:
51.96 (C6), 54.97 (C5), 119.10, 123.83, 123.89, 128.72,
129.03, 130.12, 130.23, 130.58, 130.72, 131.48, 132.88,
134.01, 134.37, 139.20, 145.84, 147.39 (Carom), 152.46
(C2), 166.85 (C4), 193.46 (Ar2C=O). Found, %: C 64.01;
H 3.59; N 7.90. [M – 1]+ 540. C29H20ClN3O6. Calculated,
%: C 64.27; H 3.72; N 7.75. M 541.9.
6-(4-Nitrophenyl)-3-phenyl-5-(4-chlorobenzoyl)-
dihyropyrimidine-2,4(1H,3H)-dione (IVa). Yield
61%, mp 243–245°C. IR spectrum, cm–1: 3280 (NH),
1725 (C=O), 1670 (C=O). 1H NMR spectrum, δ, ppm:
5.30 d (1H, H6, J 7.3 Hz), 5.58 d (1H, H5, J 7.3 Hz),
7.18–7.38 m (5Harom), 7.56 d (2Harom), 7.81 d (2Harom),
8.03 d (2Harom), 8.29 d (2Harom), 8.68 s (1H, NH).
13C NMR spectrum, δ, ppm: 51.92 (C6), 54.97 (C5),
123.83, 127.98, 128.67, 128.69, 128.98, 129.03, 130.74,
134.33, 135.37, 139.20, 145.87, 147.38 (Carom), 152.40
(C2), 164.37 (C4), 191.45 (Ar2C=O). Found, %: C 61.63;
H 3.72; N 9.26. [M – 1]+ 448. C23H16ClN3O5. Calculated,
%: C 61.41; H 3.59; N 9.34. M 449.8.
5-(4-Bromobenzoyl)-6-(3-bromophenyl)-3-
phenyldihyropyrimidine-2,4(1H,3H)-dione (IVe).
Yield 55%, mp 287–289°C. IR spectrum, cm–1: 3250
(NH), 1720 (C=O), 1660 (C=O). 1H NMR spectrum, δ,
ppm: 5.13 d (1H, H6, J 6.9 Hz), 5.53 d (1H, H5, J 6.9 Hz),
7.12 d (2Harom), 7.23–7.68 m (9Harom), 7.92 d (2Harom),
8.57 s (1H, NH). 13C NMR spectrum, δ, ppm: 51.92 (C6),
55.00 (C5), 121.83, 126.24, 127.94, 128.42, 128.68,
128.91, 130.04, 130.71, 130.84, 131.22, 131.98, 134.75,
135.42, 141.05 (Carom), 152.38 (C2), 166.99 (C4), 193.92
(Ar2C =O). Found, %: C 52.56; H 2.87; N 5.39. M+ 528.
C23H16Br2N2O3. Calculated, %: C 52.30; H 3.05; N 5.30.
M 528.2.
6-(3-Bromophenyl)-5-(4-chlorobenzoyl)-3-(4-
chlorophenyl)dihyropyrimidine-2,4(1H,3H)-dione
(IVb). Yield 47%, mp 218–219°C. IR spectrum, cm–1:
1
3275 (NH), 1720 (C=O), 1665 (C=O). H NMR
spectrum, δ, ppm: 5.15 d (1H, H6, J 7.2 Hz), 5.54 d (1H,
H5, J 7.2 Hz), 7.17–7.56 m (9Harom), 7.69 s (1Harom),
8.00 d (2Harom), 8.61 C (1H, NH). 13C NMR spectrum,
δ, ppm: 51.88 (C6), 54.85 (C5), 123.77, 127.64, 128.60,
130.83, 131.58, 132.58, 132.21, 134.32, 136.05, 137.10,
137.51, 139.18, 142.15, 145.65 (Carom), 151.91 (C2),
166.65 (C4), 192.22 (Ar2C=O). Found, %: C 53.05;
H 3.05; N 5.28. M+ 518. C23H15BrCl2N2O3. Calculated,
%: C 53.31; H 2.92; N 5.41. M 518.2.
5-(4-Bromobenzoyl)-6-(4-nitrophenyl)-3-phenyl-
dihyropyrimidine-2,4(1H,3H)-dione (IVf). Yield 64%,
mp 268–270°C. IR spectrum, cm–1: 3250 (NH), 1725
(C=O), 1680 (C=O). 1H NMR spectrum, δ, ppm: 5.31 d
(1H, H6, J 7.1 Hz), 5.56 d (1H, H5, J 7.1 Hz), 7.18 d
(2Harom), 7.39 m (3Harom), 7.68 d (2Harom), 7.81 d (2Harom),
7.97 d (2Harom), 8.25 d (2Harom), 8.68 s (1H, NH).
13C NMR spectrum, δ, ppm: 51.87 (C6), 54.98 (C5),
123.78, 127.93, 128.43, 128.61, 128.73, 128.92, 130.73,
131.94, 134.60, 135.33, 145.84, 147.37 (Carom), 152.34
(C2), 166.61 (C4), 193.64 (Ar2C=O). Found, %: C 56.11;
H 3.17; N 8.36. [M – 1]+ 493. C23H16BrN3O5. Cal-
culated, %: C 55.89; H 3.26; N 8.50. M 494.3.
6-(4-Nitrophenyl)-5-(4-chlorobenzoyl)-3-(4-
chlorophenyl)dihyropyrimidine-2,4(1H,3H)-dione
(IVc). Yield 70%, mp 255–257°C. IR spectrum, cm–1:
1
3275 (NH), 1720 (C=O), 1665 (C=O). H NMR
spectrum, δ, ppm: 5.32 d (1H, H6, J 7.2 Hz), 5.61 d (1H,
H5, J 7.2 Hz), 7.24 d (2Harom), 7.45 d (2Harom), 7.56 d
(2Harom), 7.76 d (2Harom), 8.01 d (2Harom), 8.22 d (2Harom),
8.73 s (1H, NH). 13C NMR spectrum, δ, ppm: 51.93 (C6),
54.86 (C5), 121.43, 123.82, 128.72, 129.01, 130.69, 130.87,
132.62, 134.24, 134.35, 139.22, 145.68, 147.39 (Carom),
152.18 (C2), 166.72 (C4), 193.36 (Ar2C=O). Found, %:
5-(4-Bromobenzoyl)-6-(3,4-dichlorophenyl)-3-
phenyldihyropyrimidine-2,4(1H,3H)-dione (IVg).
Yield 62%, mp 231–233°C. IR spectrum, cm–1: 3250
(NH), 1720 (C=O), 1660 (C=O). 1H NMR spectrum, δ,
ppm: 5.16 d (1H, H6, J 7.6 Hz), 5.56 d (1H, H5, J 7.6 Hz),
7.12 d (2Harom), 7.39–7.72 m ( 8Harom), 7.95 d (2Harom),
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 45 No. 5 2009

KUSHNIR et al.
760
1H NMR spectrum, δ, ppm: 1.63 s (3H, CH3S), 2.21 s
(3H, CH3), 7.04 d (2Harom), 7.25–7.41 m (5Harom), 7.55 d
(4Harom), 7.70 d (2Harom), 9.02 s (1H, NH). 13C NMR
spectrum, δ, ppm: 16.97 (CH3S), 20.37 (CH3), 78.15 q
(C2, J 29.2 Hz), 114.21 (C5), 119.71 q (CF3, J 290.5 Hz),
126.59, 127.51, 127.80, 128.20, 128.59, 129.62, 130.81,
131.22, 131.55, 136.82, 138.09, 140.98 (Carom), 151.99
(C4), 159.42 (C6), 189.57 (Ar2C=O). 19F NMR spectrum,
δ, ppm: –73.45 s (3F, CF3). Found, %: F 10.27; N 4.76.
[M + 1]+ 562. C26H20BrF3N2O2S. Calculated, %: F 10.15;
N 4.99. M 561.4.
8.52 s (1H, NH). 13C NMR spectrum, δ, ppm: 51.43 (C6),
54.75 (C5), 126.54, 128.10, 128.91, 129.72, 130.14, 131.10,
131.55, 134.76, 135.35, 137.19, 137.57, 139.41, 142.63,
143.21 (Carom), 152.28 (C2), 166.85 (C4), 193.76
(Ar2C=O). Found, %: C 53.42; H 3.08; N 5.17. [M – 1]+
517. C23H15BrCl2N2O3. Calculated, %: C 53.31; H 2.92;
N 5.41. M 518.2.
3-(3,4-Dimethylphenyl)-5-(4-methylbenzoyl)-6-
(2-fluorophenyl)dihyropyrimidine-2,4(1H,3H)-
dione (IVh). Yield 41%, mp 215–217°C. IR spectrum,
1
cm–1: 3245 (NH), 1720 (C=O), 1675 (C=O). H NMR
spectrum, δ, ppm: 2.26 s (6H, 2 CH3), 2.41 s (3H, CH3),
5.23 br.s (2H, H6 + H5), 6.90–7.51 m (9Harom), 7.95 d
(2Harom), 8.41 s (1H, NH). 13C NMR spectrum, δ, ppm:
46.85 (C6), 54.11 (C5), 124.92, 125.41, 125.51, 126.06,
128.01, 128.81, 129.45, 129.54, 129.59, 130.37, 130.45,
130.48, 132.82, 133.10, 135.99, 136.51, 144.81 (Carom),
152.72 (C2), 167.05 (C4), 194.12 (Ar2C=O). Found, %:
C 71.83; H 5.28; N 6.32. M+ 430. C26H23FN2O3.
Calculated, %: C 72.54; H 5.39; N 6.51. M 430.5.
6-Methylsulfanyl-2-(4-methylphenyl)-2-tri-
fluoromethyl-1-(4-phenoxyphenyl)-5-(4-chloro-
benzoyl)-2,3-dihyropyrimidin-4(1H)-one (VIIc).
Yield 73%, mp 199–201°C. IR spectrum, cm–1: 3220
1
(NH), 1660 (C=O). H NMR spectrum, δ, ppm: 2.05 s
(3H, CH3S), 2.38 s (3H, CH3), 6.90–7.61 m (17Harom),
9.56 s (1H, NH). 13C NMR spectrum, δ, ppm: 15.39
(CH3S), 18.51 (CH3), 79.54 q (C2, J 28.8 Hz), 113.53
(C5), 122.79 q (CF3, J 288.2 Hz), 120.36, 123.68, 128.57,
128.75, 128.79, 130.06, 130.32, 132.19, 135.85, 136.11,
138.01, 133.55, 139.25, 139.67, 142.87, 144.51 (Carom),
155.40 (C4), 161.23 (C6), 189.94 (Ar2C=O). 19F NMR
spectrum, δ, ppm: –72.7 s (3F, CF3). Found, %: F 9.47;
N 4.76. M+ 608. C32H24ClF5N2O3S. Calculated, %: F 9.36;
N 4.60. M 609.0.
5-Aroyl-1,2-diaryl-6-methylsulfanyl-2-tri-
fluoromethyl-2,3-dihydropyrimidin-4(1H)-ones
VIIa–VIId. To a solution of 4 mmol of S,N-ketene acetal
IIc–IIf in 20 ml of dry benzene was added dropwise at
stirring 0.56 ml (4 mmol) of triethylamine, then within 30
min was added 4 mmol of isocyanate Va–Vc. The reaction
mixture was stirred for 12 h, the precipitate was filtered
off, the filtrate was evaporated, and the residue was
crystallized from a mixture benzene–hexane, 1: 1, and
then from ethanol.
1-(3,4-Dimethylphenyl)-5-(4-methylbenzoyl)-6-
methylsulfanyl-2-(4-methoxyphenyl)-2-trifluoro-
methyl-2,3-dihydropyrimidin-4(1H)-one (VIId). Yield
56%, mp 187–188°C. IR spectrum, cm–1: 3230 (NH),
1
6-Methylsulfanyl-2-trifluoromethyl-1,2-bis(4-
fluorophenyl)-5-(4-chlorobenzoyl)-2,3-dihydro-
pyrimidin-4(1H)-one (VIIa). Yield 63%, mp 208–
209°C. IR spectrum, cm–1: 3250 (NH), 1650 (C=O).
1H NMR spectrum, δ, ppm: 2.03 s (3H, CH3S), 7.13–
7.79 m (12Harom), 9.63 br.s (1H, NH). 13C NMR spec-
trum, δ, ppm: 15.47 (CH3S), 78.99 q (C2, J 28.9 Hz),
118.89 (C5), 120.32 q (CF3, J 289.7 Hz), 128.68, 129.19,
129.23, 130.34, 131.11, 131.36, 131.42, 133.02, 133.12,
136.03, 136.74, 136.77, 136.88, 138.17 (Carom), 155.06
(C4), 162.08 (C6), 189.09 (Ar2C=O). 19F NMR spectrum,
δ, ppm: –73.0 s (3F, CF3), –111.7 s (1F, CF), –113.03 s
(1F, CF). Found, %: F 17.38; N 5.11. [M – 1]+ 538.
C25H16ClF5N2O2S. Calculated, %: F 17.63; N 5.20.
M 538.9.
1680 (C=O). H NMR spectrum, δ, ppm: 2.02 s (3H,
CH3S), 2.21 s (6H, 2CH3), 2.34 s (3H, CH3), 3.82 s (3H,
CH3O), 6.89–7.31 m (9Harom), 7.64 d (2Harom), 9.49 s
(1H, NH). 13C NMR spectrum, δ, ppm: 15.10 (CH3S),
18.96, 19.21, 21.12 (3CH3), 55.36 (CH3O), 79.28 q (C2,
J 28.0 Hz), 113.53 (C5), 121.14 q (CF3, J 284.0 Hz),
120.36, 124.11, 125.87, 127.14, 127.83, 128.70, 128.87,
129.31, 129.54, 130.05, 134.66, 136.58, 138.16, 143.54
(Carom), 154.49 (C4), 160.31 (C6), 190.49 (Ar2C=O).
19F NMR spectrum, δ, ppm: –72.44 s (3F, CF3). Found,
%: F 10.75; N 5.03. [M + 1]+ 541. C29H27F3N2O3S.
Calculated, %: F 10.54; N 5.18. M 540.6.
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dihyropyrimidin-4(1H)-one (VIIb). Yield 65%, mp
233–234°C. IR spectrum, cm–1: 3260 (NH), 1675 (C=O).
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