Investigations on 5-(2-aryl-2-oxo-ethylidene)-1,3-dimethylbarbituric and thiobarbituric acids: Reactions with thioureas and thioacetamide

Article abstract of DOI:10.1007/s10593-009-0365-9

Derivatives of 2-amino- and 2-methylthiazole have been synthesized by the reaction of 5-(2-aryl-2-oxoethylidene)-1,3-dimethylbarbituric and thiobarbituric acids with thioureas and thioacetamide, and also by a one-pot synthesis involving thiourea (or thioa

Full text of DOI:10.1007/s10593-009-0365-9

Chemistry of Heterocyclic Compounds, Vol. 45, No. 8, 2009
INVESTIGATIONS ON 5-(2-ARYL-2-OXO-
ETHYLIDENE)-1,3-DIMETHYLBARBITURIC
AND THIOBARBITURIC ACIDS: REACTIONS
WITH THIOUREAS AND THIOACETAMIDE
N. N. Kolos1*, L. L. Zamigaylo1, and V. I. Musatov2
Derivatives of 2-amino- and 2-methylthiazole have been synthesized by the reaction of 5-(2-aryl-
2-oxoethylidene)-1,3-dimethylbarbituric and thiobarbituric acids with thioureas and thioacetamide, and
also by a one-pot synthesis involving thiourea (or thioacetamide), arylglyoxals, 1,3-dimethyl-barbituric
(or thiobarbituric) acids. The mechanisms of the studied reactions are discussed.
Keywords: 5-(2-amino-4-arylthiazol-5-yl)-6-hydroxy-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones, 5-(2-
amino-4-arylthiazol-5-yl)-1,3-dimethylpyrimidine-2,4-diones, 5-(2-aryl-2-oxoethylidene)-1,3-dimethyl-
barbituric and 5-(2-aryl-2-oxoethylidene)thiobarbituric acids, thioacetamide, thioureas, one-pot
synthesis, cyclocondensation.
It is well known that heterocyclization involving α,β-unsaturated ketones and thioureas is a convenient
method of synthesis of 3,4-dihydropyrimidine-2-thiones [1-3]. However an alternative direction is also
mentioned in the literature for the interaction of α,β-unsaturated ketones with thioureas leading to the formation
of a dihydrothiazine ring. Nucleophilic addition of mercapto group with subsequent cyclization is characteristic
of cyclic unsaturated ketones [4, 5], and also on using N-arylthioureas in the reaction [6, 7].
Me
N
Ar
Ar
O
O
NH
O
Me
O
Me
O
N
N
N
O
N
O
R
Me
N
N
O
Me
Me
4
5
R = H, Ar
_______
* To whom correspondence should be addressed, e-mail: kolos@univer.kharkov.ua.
1Chemical Faculty V. N. Karazin Kharkiv National University, Kharkiv 61077, Ukraine.
2Institute for Single Crystals, National Academy of Sciences of Ukraine, Kharkiv 61001, Ukraine.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1220-1226, August, 2009. Original
article submitted May 29, 2008.
970
0009-3122/09/4508-0970©2009 Springer Science+Business Media, Inc.

The aim of the present investigation was the study of the reactivity of 5-(2-aryl-2-oxoethylidene)-1,3-di-
methylbarbituric or thiobarbituric acids 1a-e in relation to thioureas 2a,b and thioacetamide 3. Compounds 1
belong to the polarized olefins, the vinyl bond of which tests the effect of two electron-withdrawing fragments,
viz. a carbonyl group and a pyrimidinetrione (thioxopyrimidinedione), which generates intrigue on investigating
the direction of their interaction in reactions with 1,3-binucleophiles. It was established previously in [8], that
reactions with ureas in alcohols lead to spiropyrimidine 4, while N,N-dimethylurea under analogous
experimental conditions forms imidazolones 5.
The hypothesis has been expressed that a weak nucleophile (urea) initially attacks an exocyclic carbonyl
group of enones 1 while an increase in nucleophilicity of the reagent (N,N-dimethylurea) may change the
direction of the interaction. Such a hypothesis is in good agreement with the data obtained by us previously for
reactions of enones with a series of azabinucleophiles [9-11].
To verify the hypothesis we have studied the interaction of ketones 1 with thioureas 2. It was carried out
by briefly heating (30-45 min) the initial components in ethanol. The reaction products proved to be compounds
1
6a-i, light-yellow crystalline substances, readily soluble in polar organic solvents. In the H NMR spectra of
products 6a-e a six-proton singlet was observed for the methyl groups of the pyrimidine fragment, doublets for
the aromatic protons, and also broadened singlets in the region of 8.5 and 12.7 ppm, of intensity two and one
NH
R1
O
R1
O
N
S
N
H
R
X
Ar
R
O
HN
NH2
N
N
MeOH
Ar
+
O
O
S
–H2O
N
R
O
O
2a,b
1a–e
R
R1
NH
Ar
O
N
S
O
O
Me
R
X
N
Ar
MeOH
N
+
2a
+
O
N
O
O
N
OH
Me
7
8a,c
R
6a–i
Ar
N
O
Me
R
Me
NH2
MeOH
S
N
1a–e
+
S
X
N
R
OH
9a–e
3
MeOH
3
7
8a,b
+
+
1 a–e R = Me(Н), X = O(S); a Ar = Ph, b Ar = 4-BrC6H4, c Ar = 4-FC6H4, d Ar = 4-MeOC6H4,
e Ar = 2-thienyl; 2 a R1 = H, b R1 = 2-BrC6H4CO; 6 a–d R = Me, R1 = H, X = O, a Ar = Ph,
b Ar = 4-BrC6H4, c Ar = 4-FC6H4, d Ar = 4-MeOC6H4; e R = Me, R1 = 4-BrC6H4CO, Ar = 2-thienyl,
X = O; f–i R = H, X = S, f R1 = H, Ar = 4-BrC6H4, g R1 = H, Ar = 4-MeOC6H4, h R1 = 2-BrC6H4CO,
Ar = Ph, i 2-BrC6H4CO, Ar = 4-FC6H4; 8 a Ar = Ph, b Ar = 4-BrC6H4, c Ar = 4-FC6H4; 9 a–c R = Me, a–c X = O,
a Ar = Ph, b Ar = 4-BrC6H4, c Ar = 4-FC6H4; d, e R = H, X = S, d Ar = 4-MeOC6H4, e Ar = 2-thienyl
971

proton respectively, disappearing on carrying out deuterium exchange. In the IR spectra (KBr disks) of
compounds 6a,d,g two absorption bands of moderate intensity were seen at 3220 and 3320 cm-1, confirming the
presence of a primary amino group. In the mass spectra of compounds 6a,c,h peaks were displayed for the
molecular ions, and their fragmentation confirmed the formation of a thiazole ring.
The products of reacting enones 1 with thioureas 2 are therefore 5-(2-amino-4-arylthiazol-5-yl)-6-hydroxy-
1,3-dimethylpyrimidine-2,4-diones 6a-e or 5-(2-amino-4-arylthiazol-5-yl)-6-hydroxy-2-thioxo-2,3-dihydro-
pyrimidin-4(1H)-ones 6f-i. The synthesized compounds 6a-i and the imidazolin-2-ones 5 exist in DMSO-d6
solution in the 6-hydroxy form. In thiazoles 6a-d the clear influence is observed of conjugation of the
p-substituent in the aromatic nucleus on the chemical shift of the proton of the hydroxyl group (see
Experimental). However the introduction of electron-withdrawing groups into the molecule (6e,h,i) increases the
1
acidity of the 6-hydroxyl group. This does not appear in the H NMR spectra due to the rapid exchange with
water present in the DMSO-d6. Thiazoles 6a,c were also obtained by the one-pot method using acid 7,
arylglyoxals 8a,c and thiourea, however the reaction time doubled. In addition, in the case of the interaction in
stages the yields were 70-80%, while under one-pot conditions of synthesis the yield of product 6 was reduced
significantly (see Experimental). Thioacetamide 3 reacts analogously with ketones 1a-e forming thiazoles 9a-e.
1
The structure of compounds 9a-e was confirmed by spectral methods. In the H NMR spectra singlets
were present for the methyl groups of the pyrimidine and thiazole rings, and multiplets for the aromatic protons.
The signal of the 6-hydroxyl group of the uracil ring is in this case readily exchanged with water and is not seen
in the spectrum. In the mass spectrum of product 9b peaks were present for the molecular ion with m/z 407
(409).
The presence of the amino group in thiazoles 6 was additionally confirmed by an acylation reaction.
Boiling compounds 6a,b in acetic anhydride did not lead to the N-acetyl derivative, while reaction in the
presence of sulfuric acid (procedure for acylating difficultly acylable amines [12]) enabled amides 10a,b to be
synthesized.
Ar
Ar
N
N
O
O
H
N
NH2
Me
O
Me
O
(MeCO)2O
H2SO4
S
S
N
N
Me
N
OH
O
N
OH
Me
Me
10a,b
6a,b
6, 10 a Ar = Ph, b Ar = 4-BrC6H4
Consequently the ketones 1 investigated by us are characterized by a vinyl group with a large
π-deficiency in comparison with chalcones, which also leads to a regioselective interaction with 1,3-N,S-
binucleophiles. Thioureas and thioacetamide react with the electron-deficient C(2) atom of the vinylic bond of
ketones 1 via the sulfur atom with the highest nucleophilic strength. This enables convenient methods to be
developed for the synthesis of new derivatives of 2-amino- and 2-methylthiazole 6a-i and 9a-e respectively,
including a one-pot, starting from dimethylbarbituric (or thiobarbituric) acid, arylglyoxals and thioureas (or
thioacetamide).
EXPERIMENTAL
1
The IR spectra were obtained on a Specord IR-75 spectrometer in KBr disks. The H and 13C NMR
spectra were measured with a Varian VX-200 Mercury instrument (200 and 50 MHz respectively) in DMSO-d6,
internal standard was TMS. The mass spectra were obtained on a Hewlett-Packard LC/MSD 1100 instrument
972

with ionization by electron impact (voltage 70 eV). Elemental analysis was carried out on a LECO CHNS 900
instrument. Melting points were determined on a Koefler block. A check on the progress of reactions and the
purity of the obtained compounds was carried out by TLC on Silufol UV-254 plates in the system toluene–ethyl
acetate, 1:1, and toluene–hexane, 1:10 (visualization with iodine vapor).
5-(2-Amino-4-arylthiazol-5-yl)-6-hydroxy-1,3-dimethylpyrimidine-2,4-diones 6a-e, 5-(2-Amino-
4-arylthiazol-5-yl)-6-hydroxy-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones 6f-i (General Method). A.
Equimolar quantities of enone 1 and thiourea 2 (about 1 mmol) were boiled in ethanol (10 ml) for 30-45 min.
The resulting light-yellow solid was filtered off and crystallized from EtOH.
B. (one-pot). Arylglyoxal monohydrate 8 and thiourea 2 (about 1 mmol) were added to a solution of
compound 7 (1 mmol) in EtOH (10 ml). The reaction mixture was boiled for 30 min to 1 h until precipitation
from the hot solution of a solid, which was crystallized from EtOH.
5-(2-Amino-4-phenylthiazol-5-yl)-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione (6a). Yield
76% (A), 40% (B); mp 300-301oC (EtOH). IR spectrum, ν, cm-1: 1622 (C=C), 1665 (C=O), 1676 (C=O), 3220
s
as
(NH2 ), 3326 (NH2 ). 1H NMR spectrum, δ, ppm (J, Hz): 3.01 (6H, s, CH3); 7.26-7.36 (3H, m, p- + m-Ph); 7.42
(2H, d, J = 7.2, o-Ph); 8.55 (2H, s, NH2); 12.76 (1H, br. s, OH). 13C NMR spectrum, δ, ppm: 27.8 (2N–CH3);
78.0 (C-5 Pyr); 119.3 (C-5 thiazole); 132.0 (C-4 thiazole); 127.6, 128.6, 128.8, 131.6 (Ph); 153.1, 161.8, 168.5
(C=O); 167.0 (C-2 thiazole). Mass spectrum, m/z (Irel, %): 330 [M]+ (100), 331 [M+1]+ (8), 216 (100), 187 (8),
160 (8), 155 (10), 146 (37), 102 (13), 77 (13). Found, %: C 54.44; H 4.32; N 16.80. C15H14N4O3S. Calculated,
%: C 54.53; H 4.27; N 16.96.
5-[2-Amino-4-(4-bromophenyl)thiazol-5-yl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
1
(6b). Yield 64%; mp >300oC (EtOH). H NMR spectrum, δ, ppm (J, Hz): 3.01 (6H, s, CH3); 7.43 (2H, d,
J = 8.4, o-Ar); 7.52 (2H, d, J = 8.4, m-Ar); 8.55 (2H, s, NH2); 12.51 (1H, br. s, OH). Found, %: C 43.94; H 3.13;
N 13.76. C15H13BrN4O3S. Calculated, %: C 44.02; H 3.20; N 13.69.
5-[2-Amino-4-(4-fluorophenyl)thiazol-5-yl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
(6c). Yield 72% (A), 39% (B); mp >300oC (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 3.01 (6H, s, CH3); 7.17
(2H, t, J = 8.8, m-Ar); 7.41-7.49 (2H, m, o-Ar); 8.57 (2H, s, NH2); 12.62 (1H, br. s, OH). Mass spectrum, m/z
(Irel, %): 348 [M]+ (100), 349 [M+1]+ (16), 234 (100), 235 (12), 172 (12), 164 (64), 120 (13), 107 (7). Found,
%: C 51.64; H 3.70; N 15.99. C15H13FN4O3S. Calculated, %: C 51.72; H 3.76; N 16.08
5-[2-Amino-4-(4-methoxyphenyl)thiazol-5-yl)]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-
dione (6d). Yield 61%; mp >300oC (EtOH). IR spectrum, ν, cm-1: 1628 (C=C), 1668 (C=O), 1675 (C=O), 3225
s
as
1
NH2 ), 3323 (NH2 ). H NMR spectrum, δ, ppm (J, Hz): 3.01 (6H, s, CH3); 3.73 (3H, s, OCH3); 6.91 (2H, d,
J = 8.4, m-Ar); 7.37 (2H, d, J = 8.4, o-Ar); 8.57 (2H, s, NH2); 12.44 (1H, br. s, OH). Found, %: C 53.40; H 4.53;
N 15.49. C16H16N4O4S. Calculated, %: C 53.32; H 4.47; N 15.55.
N-[5-(6-Hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-(2-thienylthiazol-2-yl]-
1
2-bromobenzamide (6e). Yield 48%; mp >300oC (EtOH). H NMR spectrum, δ, ppm (J, Hz): 3.08 (6H, s,
CH3); 7.28-7.50 (3H, m, thienyl); 7.56-7.64 (3H, m, m-, p-BrC6H4); 7.72 (1H, d, J = 7.2, o-BrC6H4); 12.69 (1H,
s, NH). Found, %: C 46.35; H 2.83; N 10.84. C20H15BrN4O4S2. Calculated, %: C 46.25; H 2.91; N 10.79.
5-[2-Amino-4-(4-bromophenyl)thiazol-5-yl]-6-hydroxy-2-thioxo-2,3-dihydropyrimidin-4(1H)-one
(6f). Yield 3%; mp 298-299oC (EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 7.33 (2H, d, J = 8.4, o-Ar); 7.53 (2H,
d, J = 8.4, m-Ar); 8.39 (2H, s, NH2); 10.89 (2H, s, NH); 12.80 (1H, br. s, OH). Found, %: C 39.24; H 2.20;
N 14.19. C13H9BrN4O2S2. Calculated, %: C 39.30; H 2.28; N 14.10.
5-[2-Amino-4-(4-methoxyphenyl)thiazol-5-yl]-6-hydroxy-2-thioxo-2,3-dihydropyrimidin-4(1H)-
one (6g). Yield 57%; mp 281-282oC (EtOH). IR spectrum, ν, cm-1: 1195 (C=S), 1620 (C=C), 1667 (C=O), 3250
s
as
1
(NH2 ), 3350 (NH2 ). H NMR spectrum, δ, ppm (J, Hz): 3.73 (3H, s, CH3); 6.92 (2H, d, J = 8.4, o-Ar); 7.36
(2H, d, J = 8.4, m-Ar); 8.56 (2H, s, NH2); 10.82 (2H, s, NH); 12.82 (1H, br. s, OH). Found, %: C 48.34; H 3.56;
N 16.12. C14H12N4O3S2. Calculated, %: C 48.26; H 3.47; N 16.08.
973

N-[5-(6-Hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-phenylthiazol-2-yl]-2-bromo-
benzamide (6h). Yield 45%; mp >300oC (from EtOH). 1H NMR spectrum, δ, ppm (J, Hz): 7.24 (1H, m, p-Ph);
7.30-7.49 (4H, m, o- + m-Ph); 7.56-7.62 (3H, m, m-, p-BrC6H4); 7.72 (1H, d, J = 7.0, o-BrC6H4); 12.01 (2H, s,
NH); 12.71 (1H, s, NH). Mass spectrum, m/z (Irel, %): 500 [M]+ (50), 502 [M]+ (50), 421 (5), 201 (10), 185
(97), 179 (100), 157 (35), 105 (6). Found, %: C 47.84; H 2.69; N 11.12. C20H13BrN4O3S2. Calculated, %:
C 47.91; H 2.61; N 11.17.
N-[4-(4-Fluorophenyl)-5-(6-hydroxy-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)thiazol-2-yl]-
2-bromobenzamide (6i). Yield 49%; mp >300oC (EtOH). IR spectrum, ν, cm-1: 1193 (C=S), 1620 (C=C), 1655
(C=O), 1692 (C=O), 3403 (NH). 1H NMR spectrum, δ, ppm (J, Hz): 7.19 (2H, t, J = 8.4, o-Ar); 7.44-7.64 (5H,
m, m-Ar + m-, p-BrC6H4); 7.72 (1H, d, J = 6.6, o-BrC6H4); 12.17 (2H, s, NH); 12.76 (1H, s, NH). Found, %:
C 46.32; H 2.40; N 10.86. C20H12BrFN4O3S2. Calculated, %: C 46.25; H 2.33; N 10.79.
6-Hydroxy-1,3-dimethyl-5-(4-aryl-2-methylthiazol-5-yl)pyrimidine-2,4-(1H,3H)-diones 9a-c and 6-
Hydroxy-5-[4-aryl-2-methylthiazol-5-yl]-2-thioxo-2,3-dihydropyrimidin-4(1H)-ones
9d,e
(General
Method). A. A mixture of enone 1 (1 mmol) and thioacetamide 3 (1 mmol) in MeOH (10-15 ml) was boiled for
15-30 min. The finely crystalline white solid precipitated on cooling was filtered off and washed on the filter or
crystallized from MeOH.
B. (one-pot). Arylglyoxal monohydrate 8 (1 mmol) and thioacetamide 3 (1 mmol) were added to
compound 7 (1 mmol) in MeOH (10 ml). The reaction mixture was boiled for 1 h until precipitation of a white
solid from the hot solution. The solid was crystallized from MeOH.
6-Hydroxy-1,3-dimethyl-5-(2-methyl-4-phenylthiazol-5-yl)pyrimidine-2,4(1H,3H)-dione (9a). Yield
1
51% (A), 73% (B); mp 279-280oC (MeOH). IR spectrum, ν, cm-1: 1619 (C=C), 1670 (C=O), 1687 (C=O). H
NMR spectrum, δ, ppm (J, Hz): 2.77 (3H, s, CH3); 3.06 (6H, s, CH3); 7.27-7.38 (3H, p-, m-Ph); 7.51 (2H, d,
J = 6.8, o-Ph). Found, %: C 58.44; H 4.62; N 12.83. C16H15N3O4S. Calculated, %: C 58.34; H 4.59; N 12.76.
5-[4-(4-Bromophenyl)-2-methylthiazol-5-yl]-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
1
(9b). Yield 56% (A), 75% (B); mp 288-289oC (MeOH). H NMR spectrum, δ, ppm (J, Hz): 2.74 (3H, s, CH3);
3.06 (6H, s, CH3); 7.46 (2H, d, J = 8.7, o-Ar); 7.53 (2H, d, J = 8.7, m-Ar). Mass spectrum, m/z (Irel, %): 407
[M]+ (50), 409 [M]+ (50), 235 (12), 214 (100), 198 (28), 183 (21), 145 (9), 107 (7). Found, %: C 46.98; H 3.54;
N 10.34. C16H14BrN3O3S. Calculated, %: C 47.07; H 3.46; N 10.29.
6-Hydroxy-1,3-dimethyl-5-[2-methyl-4-(4-fluorophenyl)thiazol-5-yl]pyrimidine-2,4(1H,3H)-dione
1
(9c). Yield 39%; mp 251-252oC (MeOH). IR spectrum, ν, cm-1: 1621 (C=C), 1675 (C=O), 1689 (C=O). H
NMR spectrum, δ, ppm (J, Hz): 2.75 (3H, s, CH3); 3.06 (6H, s, CH3); 7.17 (2H, t, J = 8.8, m-Ar); 7.51-7.58 (2H,
m, o-Ar). Found, %: C 55.24; H 3.99; N 12.03. C16H14FN3O3S. Calculated, %: C 55.32; H 4.06; N 12.10.
6-Hydroxy-5-[2-methyl-4-(4-methoxyphenyl)thiazol-5-yl]-2-thioxo-2,3-dihydropyrimidin-4(1H)-
1
one (9d). Yield 55%; mp >300oC (MeOH). H NMR spectrum, δ, ppm (J, Hz): 2.75 (3H, s, CH3); 3.75 (3H, s,
OCH3); 6.93 (2H, d, J = 8.6, m-Ar); 7.44 (2H, d, J = 8.6, o-Ar); 11.49 (2H, s, NH). Found, %: C 51.78; H 3.83;
N 12.01. C15H13N3O3S. Calculated, %: C 51.86; H 3.77; N 12.10.
6-Hydroxy-5-[2-methyl-4-(2-thienyl)thiazol-5-yl]-2-thioxo-2,3-dihydropyrimidin-4(1H)-one (9e).
1
Yield 37%; mp >300oC (MeOH). H NMR spectrum, δ, ppm (J, Hz): 2.64 (2H, s, CH3); 7.02 (1H, t, J = 3.8;
J = 4.6, β-thienyl); 7.27 (1H, d, J = 2.8, β-thienyl); 7.42 (1H, d, J = 4.6, α-thienyl); 12.01 (2H, s, NH). Found,
%: C 44.49; H 2.73; N 13.04. C12H9N3O2S3. Calculated, %: C 44.56; H 2.80; N 12.99.
N-[5-(6-Hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-4-phenylthiazol-2-yl]-
acetamide (10a). Conc. H2SO4 (2 drops) was added to a solution of compound 6a (1 mmol) in Ac2O (2 ml) and
the mixture was boiled for 30 min. The reaction mixture was poured onto ice and the obtained solid crystallized
1
from EtOH. Yield 76%; mp 280-282oC (EtOH). H NMR spectrum, δ, ppm, (J, Hz): 2.13 (3H, s, CH3); 3.15
(6H, s, CH3); 7.21-7.30 (3H, m, p-, m-Ph); 7.61 (2H, d, J = 6.8, o-Ph); 12.07 (1H, s, NH). Found, %: C 54.90;
H 4.30; N 14.97. C17H16N4O4S. Calculated, %: C 54.83; H 4.33; N 15.04.
974

N-[4-(4-Bromophenyl)-5-(6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl]thiazol-
1
2-yl)acetamide (10b) was obtained analogously. Yield 69%; mp 254-256oC (EtOH). H NMR spectrum, δ,
ppm, (J, Hz): 2.13 (3H, s, CH3); 3.14 (6H, s, 2CH3); 7.49 (2H, d, J = 8.0, o-Ar); 7.55 (2H, d, J = 8.0, m-Ar);
12.05 (1H, s, NH). Found, %: C 45.30; H 3.42; N 12.33. C17H15BrN4O4S. Calculated, %: C 45.24; H 3.35;
N 12.41.
REFERENCES
1.
2.
3.
4.
5.
6.
7.
8.
J. Joule and K. Mills, Chemistry of Heterocyclic Compounds [Russian translation], Mir, Moscow, 2004
M. R. Mahmound and H. M. F. Markour, Synth. Commun., 26, 3799 (1996).
H. H. Sayed, Indian J. Chem., 37B, 1054 (1998).
G. Osske, D. Szabo, and T. Lorand, Pharmazie, 43, 164 (1988).
P. Perjesi, G. Batta, and A. Foeldesi, Monatsh. Chem., 125, 433 (1994).
M. Augustin and P. Jechke, J. Prakt. Chem., 329, 626 (1987).
H. Singh, S. Kumar, and P. Singh, J. Chem. Res. (miniprint), 1641 (1984).
L. Gozalishvili, T. Beryozkina, I. Omelchenko, R. Zubatyuk, O. Shishkin, and N. Kolos, Tetrahedron,
64, 8759 (2008).
9.
N. N. Kolos, V. D. Orlov, E. Ya. Yuzefovskaya, F. G. Yaremenko, N. P. Vorob'eva, O. V. Shishkin,
Yu. T. Struchkov, and S. M. Ivkov, Khim. Geterotsikl. Soedin., 950 (1995). [Chem. Heterocycl. Comp.,
31, 827 (1995)].
10.
11.
12.
N. N. Kolos, V. D. Orlov, D. Arisa, O. V. Shishkin, Yu. T. Struchkov, and N. P. Vorob'eva, Khim.
Geterotsikl. Soedin., 87 (1996). [Chem. Heterocycl. Comp., 32, 78 (1996)].
N. N. Kolos, V. D. Orlov, V. A. Chebanov, O. V. Shishkin, V. P. Kuznetsov, and A. Yu. Kulikov, Khim.
Geterotsikl. Soedin., 978 (1996). [Chem. Heterocycl. Comp., 32, 838 (1996)].
K. Weygand and G. Hilgetag, Organisch-chemische Verkunst, Verlag, Berlin (1964). [Experimental
Methods in Organic Chemistry [Russian translation], Khimiya, Moscow (1968)].
975