Synthesis of 2-(N-benzoylimino)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl) thiazoles

Full text of DOI:10.1007/s10593-014-1437-z

Chemistry of Heterocyclic Compounds, Vol. 49, No. 12, March, 2014 (Russian Original Vol. 49, No. 12, December, 2013)
SYNTHESIS OF 2-(N-BENZOYLIMINO)-N-(9,10-DIOXO-
9,10-DIHYDROANTHRACEN-1-YL)THIAZOLES
M. V. Stasevych1*, V. I. Zvarych1, O. V. Stan'ko1, M. V. Vovk2, and V. P. Novikov1
Keywords: 9,10-anthraquinone, anthracenylbenzoyliminothiazoles, N-benzoylthioureas, α-bromoacetone.
N-Aroylthioureas hold a significant promise for the synthesis of such heterocycles as imidazolidine-
2-thiones [1, 2], 2-aroyliminothiazolines [3-5], 1,2,4-triazoles [6], 1,3-thiazines [7], and indeno[1,2-d]-
[1,3]thiazepines [8]. Of particular interest are 2-iminothiazolines, which are characterized by a wide range of
biological properties [9-11]. For example, the thiazol-2-imine fragment is a structural fragment in muscarinic
agonists, as well as antifungal, hypolipidemic, antidiabetic, anti-inflammatory, analgesic, and anti-shistosomiasis
compounds [5]. Thiazoline derivatives are also used as insecticides and plant growth regulators [5].
The reaction of N,N'-disubstituted thioureas with α-bromo ketones has been described in the literature
[5, 12], and it provides access to various N-substituted 2-iminothiazoles. However, 2-iminothiazoles with
9,10-dioxo-9,10-dihydroanthracenyl substituents at position 3 of the heterocycle remain hitherto unknown. The
pronounced biological properties of anthraquinone derivatives [13-15] motivate the search for hybrid structures
that include both anthraquinone and thiazole ring systems.
Based on these considerations, we treated our previously described N-benzoyl-N'-(9,10-dioxo-
9,10-dihydroanthracen-1-yl)thioureas 1а-е [16] with in situ generated α-bromoacetone in the presence of
triethylamine and obtained the 2-(N-benzoylimino)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thiazoles 2а-е in
48-68% yields. The formation of 2-(N-benzoyl)imine type thiazoles through a cyclocondensation with the
participation of aminoanthracene nitrogen atom was in agreement with the recently described reactions of
N-aryl-N'-aroylthioureas with α-halo ketones [4, 12, 13].
1
The Н NMR spectra of compounds 2а-е contained thiazole H-5 proton singlets at 6.89-7.01 ppm and
methyl group singlets at 1.97-2.04 ppm, besides the CH signals of the aromatic rings. The formation of a thiazole
ring was also clearly confirmed by the 13С spectra containing the characteristic С-4 singlets at 106.1-107.2 ppm, С-5
singlets at 139.3-144.9 ppm, and С-2 singlets at 168.2-169.7 ppm. The 13C signals of the thiazole 4-СН3 substituent
were found at 13.7-14.2 ppm, which is typical for 3-aryl-2-benzoylimino-4-methyl-1,3-thiazolines [4, 5].
Thus, we have prepared new 2-(N-benzoylimino)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thiazoles
by a novel route, starting from N-benzoyl-N'-(9,10-dioxo-9,10-dihydroanthracen-1-yl)thioureas.
_______
*To whom correspondence should be addressed, e-mail: vnovikov@polynet.lviv.ua.
1Lviv'ska Polytechnica National University, 12 S. Bandery St., Lviv 79013, Ukraine.
2Institute of Organic Chemistry, National Academy of Sciences of Ukraine, 5 Murmanska St., Kyiv 02094,
Ukraine; e-mail: mvovk@ioch.kiev.ua.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1976-1978, December, 2013.
Original article submitted November 7, 2013.
0009-3122/14/4912-1831©2014 Springer Science+Business Media New York
1831

S
O
S
Me
O
N
H
O
O
O
HN
N
Ph
N
R1
Br2, Me2CO
Et3N, 2 h
R1
Ph
R2
1a–e
R3
O
R2
2a–e
R3
a R1 = R2 = R3 = H; b R1 = Me, R2 = R3 = H; c R1 = R3 = H, R2 = NH2;
d R1 = R2 = H, R3 = NH2; e R1 = R3 = H, R2 = NHCOPh
IR spectra were recorded on a Specord М80 spectrometer in KBr pellets. 1Н and 13С NMR spectra were
acquired on a Varian Mercury 400 instrument (400 and 100 MHz, respectively) at 25°C in DMSO-d6, with TMS
as internal standard. Chromatography with mass spectrometry was performed on an Agilent 1100 Series
chromatograph, equipped with an Agilent LC/MSDSL mass selective detector. A Zorbax SB-C18 column (1.8 μ,
4.6×15 mm) was used with a mobile phase gradient from acetonitrile–water–0.1% TFA (system A) to water–0.1%
TFA (system B). Chemical ionization was used at ambient pressure. The reaction progress was monitored by
TLC on Silufol UV-254 plates with a 6:1 benzene–acetonitrile mobile phase. The elemental analysis was
performed on a Thermo Finnigan Flash EA 1112 instrument.
Preparation of N-[3-(9,10-Dioxo-9,10-dihydroanthracen-1-yl)-4-methyl-1,3-thiazol-2(3H)-ylidene]-
benzamides 2а-е (General Method). A solution of bromine (0.0384 ml, 0.749 mmol) in acetone (10 ml) was
added with stirring over 15 min to a suspension of N-benzoylthiourea 1а-е (0.749 mmol) and triethylamine
(0.104 ml, 0.749 mmol) in acetone (30 ml). The reaction mixture was maintained at the room temperature for
2 h, the precipitate that formed was filtered off, washed with acetone, then with water, dried, and crystallized
from toluene.
N-[3-(9,10-Dioxo-9,10-dihydroanthracen-1-yl)-4-methyl-1,3-thiazol-2(3H)-ylidene]benzamide (2а).
Yield 68%; mp 210-211°C. IR spectrum, ν, cm-1: 1680, 1631 (С=О quinone), 1685 (С=О amide), 1471 (C=N).
1H NMR spectrum, δ, ppm (J, Hz): 1.99 (3Н, s, СН3); 6.92 (1Н, s, СН=); 6.94-7.02 (3Н, m, H Ar); 7.68-7.70
(3Н, m, H Ph); 7.91-8.05 (2Н, m, H Ph); 8.15-8.28 (3Н, m, H Ar); 8.53 (1Н, d, J = 8.4, H Ar). 13C NMR
spectrum, δ, ppm: 14.2 (CH3СН=); 106.7 (CН=); 126.8, 127.3, 127.5, 128.4 (C Ar); 128.7, 129.1, 129.3,
(C Ph); 131.5 (С Ar); 132.4 (C Ph); 133.5, 133.6, 134.4, 134.9, 135.2 (C Ar); 135.8 (C Ph); 137.8 (C–N);
143.3 (CH3СН=); 168.5 (C=N); 173.5 (COPh); 181.8 (CO); 182.5 (CO). Mass spectrum, m/z (Irel, %): 425
[M+H]+ (69). Found, %: С 70.64; Н 3.87; N 6.71; S 7.59. C25H16N2O3S. Calculated, %: С 70.74; Н 3.80;
N 6.60; S 7.55.
N-[4-Methyl-3-(2-methyl-9,10-dioxo-9,10-dihydroanthracen-1-yl)-1,3-thiazol-2(3H)-ylidene]benzami-
de (2b). Yield 51%; mp 206-207°C. IR spectrum, ν, cm-1: 1681, 1623 (С=О quinone), 1670 (С=О amide), 1397
1
(C=N). H NMR spectrum, δ, ppm (J, Hz): 1.99 (3Н, s, СН3); 2.17 (3Н, s, СН3); 7.01 (1Н, s, СН=); 7.24-7.27
(2Н, m, H Ph); 7.31-7.40 (1Н, m, H Ph); 7.67-7.74 (2Н, m, H Ph); 7.85-7.90 (2Н, m, H Ar); 8.02 (1Н, d,
13
J = 7.5, H Ar); 8.14 (1Н, d, J = 7.5, H Ar); 8.21 (1Н, d, J = 7.5, H Ar); 8.44 (1Н, d, J = 7.6, H Ar). C NMR
spectrum, δ, ppm: 13.9 (CH3СН=); 17.7 (CH3); 106.1 (CН=); 126.8, 127.3, 127.6, 128.5 (C Ar); 128.8, 128.9,
129.0, 129.1 (C Ph); 131.8 (С Ar); 132.8 (C Ph); 133.7, 133.9, 134.0, 135.0, 135.1 (C Ar); 135.2 (C Ph); 137.1
(C Ar); 137.3 (C–N); 144.9 (CH3СН=); 168.7 (C=N); 173.1 (COPh); 182.1 (CO); 182.4 (CO). Mass spectrum, m/z
(Irel, %): 439 [M+H]+ (97). Found, %: С 71.31; Н 4.01; N 6.41; S 7.59. C26H18N2O3S. Calculated, %: С 71.22;
Н 4.14; N 6.39; S 7.31.
N-[3-(4-Amino-9,10-dioxo-9,10-dihydroanthracen-1-yl)-4-methyl-1,3-thiazol-2(3H)-ylidene]benz-
amide (2с). Yield 50%; mp 296-297°С. IR spectrum, ν, cm-1: 3365, 3307 (NH2), 1683, 1625 (С=О quinone),
1
1650 (С=О amide), 1450 (C=N). H NMR spectrum, δ, ppm (J, Hz): 1.98 (3Н, s, СН3); 6.89 (1Н, s, СН=);
7.20-7.31 (3Н, m, H Ar, NH2); 7.38-7.41 (2Н, m, H Ar); 7.49-7.57 (3Н, m, H Ph); 7.73-7.81 (2Н, m,
1832

H Ph); 7.87-7.91 (2Н, m, H Ar); 8.23 (1Н, d, J = 7.6, H Ar). 13C NMR spectrum, δ, ppm: 13.7 (CH3СН=); 107.2
(CН=); 114.5, 125.3, 126.1, 127.2 (C Ar); 128.1, 128.2, 129.3, 129.4 (C Ph); 130.1 (C–N); 130.9, 131.3 (C Ar);
132.3 (C Ph); 133.1, 133.2, 133.5, 133.8 (C Ar); 136.1 (C Ph); 139.8 (CH3СН=); 147.8 (C–NH2); 169.7 (C=N);
174.5 (COPh); 183.1 (CO); 184.3 (CO). Mass spectrum, m/z (Irel, %): 440 [M+H]+ (73). Found, %: С 68.41;
Н 4.01; N 9.69; S 7.37. C25H17N3O3S. Calculated, %: С 68.32; Н 3.90; N 9.56; S 7.30.
N-[3-(5-Amino-9,10-dioxo-9,10-dihydroanthracen-1-yl)-4-methyl-1,3-thiazol-2(3H)-ylidene]benz-
1
amide (2d). Yield 69%; mp 232-233°С. H NMR spectrum, δ, ppm (J, Hz): 1.97 (3Н, s, СН3); 6.92 (1Н, s,
СН=); 7.15-7.26 (5Н, m, H Ar); 7.34-7.46 (2Н, m, H Ph); 7.63-7.72 (3Н, m, H Ph, NH2); 7.83-7.91(1Н, m,
H Ar); 8.13-8.16 (1Н, m, H Ar); 8.53 (1Н, d, J = 8.4, H Ar). 13C NMR spectrum, δ, ppm: 13.8 (CH3СН=); 106.8
(CН=); 111.9, 115.4, 120.1, 122.2, 123.7 (C Ar); 128.1, 129.2, 129.3, 129.4, 132.4 (C Ph); 132.9, 133.4, 135.0,
135.3, 135.7 (C Ar); 136.1 (C Ph); 138.2 (C–N); 139.3 (CH3СН=); 151.8 (C–NH2); 168.2 (C=N); 174.5
(COPh); 183.6 (CO); 184.4 (CO). Mass spectrum, m/z (Irel, %): 440 [M+H]+ (82). Found, %: С 68.38; Н 3.95;
N 9.62; S 7.35. C25H17N3O3S. Calculated, %: С 68.32; Н 3.90; N 9.56; S 7.30.
N-[3-(4-Benzamido-9,10-dioxo-9,10-dihydroanthracen-1-yl)-4-methyl-1,3-thiazol-2(3H)-ylidene]benz-
amide (2е). Yield 48%; mp 198°С. IR spectrum, ν, cm-1: 3345 (N–H), 1683, 1625 (С=О quinone), 1650, 1661
(С=О amide), 1450 (C=N). 1H NMR spectrum, δ, ppm (J, Hz): 2.04 (3Н, s, СН3); 6.95 (1Н, s, СН=); 7.31-7.40
(1Н, m, H Ar); 7.72-8.27 (11Н, m, H Ph, H Ar); 8.83-8.92 (2Н, m, H Ar); 9.29-9.41 (2Н, m, H Ar); 13.30 (1Н,
13
s, NH). C NMR spectrum, δ, ppm: 14.1 (CH3СН=); 106.3 (CН=); 118.2, 125.1, 126.5 (C Ar); 127.2, 127.3,
128.0, 128.1, 128.8, 128.9, 129.3, 129.4 (C Ph); 129.5, 130.3 (C Ar); 132.4, 132.5 (C Ph); 133.0 (C Ar); 133.2
(C–NH); 133.3 (C Ph); 133.4, 133.7, 134.3, 136.2 (C Ar); 136.0 (C Ph); 138.2 (C–N); 138.8 (CH3СН=); 165.7
(CO); 167.8 (C=N); 174.4 (COPh); 182.6 (CO); 184.5 (CO). Found, %: С 70.76; Н 3.96; N 7.68; S 5.87.
C32H21N3O4S. Calculated, %: С 70.70; Н 3.89; N 7.73; S 5.90.
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