Carbon bisulfide in synthesis of thiazolo[3,4-a]quinoxalines based on 3-(α-chlorobenzyl)quinoxalin-2-(1H)-ones [8]

Full text of DOI:10.1023/B:COHC.0000023785.83340.ac

Chemistry of Heterocyclic Compounds, Vol. 40, No. 1, 2004
CARBON DISULFIDE IN SYNTHESIS OF
THIAZOLO[3,4-a]QUINOXALINES BASED ON
3-(α-CHLOROBENZYL)QUINOXALIN-2-(1H)-ONES
A. A. Kalinin and V. A. Mamedov
Keywords: xanthogenates, carbon disulfide, thiazolo[3,4-a]quinoxalines, quinoxalines, thiazoles.
A widely used method for obtaining thiazole derivatives is the Cook–Heilbron synthesis [1], in which
C–S and C–C–N moieties are used to construct the ring in condensation of carbon disulfide with α-amino nitriles
and α-amino amides, leading to 5-aminothiazole derivatives that are either unsubstituted or substituted in the
position 4. We have found that 3-(α-chlorobenzyl)quinoxalin-2-(1H)-ones 1 [2], because of the
α-chlorobenzylimine moieties which function as a triatomic synthon C+–C–N–, when reacted with hydrogen
disulfide yield condensed thiazole derivatives: thiazolo[3,4-a]quinoxalines 2, 3. Since the reactions are carried
out in the presence of KOH in methanol solution, formation of a thiazoloquinoxaline system probably occurs via
xanthogenates 4, which then undergo intramolecular cyclocondensation. In order to confirm this hypothesis, we
synthesized the xanthogenates 4a,b and showed that they can undergo ring closure to form thiazolo[3,4-a]-
quinoxalines under conditions of not only base catalysis but also acid catalysis, and the latter variant is preferred.
Depending on both the reaction conditions and the nature of the aryl group of the substituent at the position 3,
1-thioxo (2) or 1-oxo (3) derivatives of thiazolo[3,4-a]quinoxalines are formed. The best yields of
thiazolo[3,4-a]quinoxalines are achieved when the reactions are carried out in CF3COOH; in this case, boiling
solutions of xanthogenates 4a,b in CF3COOH for two hours leads exclusively to 1-oxothiazolo[3,4-a]-
quinoxalines 3a,b, while boiling for half an hour makes it possible, when Ar = Ph, to obtain the 1-thioxo
X
S
Ar
O
N
N
MeOH, KOH, CS2, ∆, 7 h
Ar
Cl
N
H
N
H
O
1
MeOH,
KOH, CS2
2 (X = S)
3 (X = O)
+
H
Ar
O
S
N
S
OMe
N
H
4a,b
4 a Ar = Ph, b Ar = 2,4-Cl2C6H3
__________________________________________________________________________________________
A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Science Center, Russian Academy of
Sciences, Kazan 420088; e-mail: mamedov@iopc.kcn.ru. Translated from Khimiya Geterotsiklicheskikh
Soedinenii, No. 1, pp. 133-135, January, 2004. Original article submitted July 23, 2003.
0009-3122/04/4001-0129©2004 Plenum Publishing Corporation
129

derivative 2a. We do not get good results if instead of CF3COOH we use AcOH or 6.1 M HCl, in which
thiocyanate and diphenylisothioureide analogs of compound 4a readily undergo intramolecular cyclization to
form 1-iminothiazoloquinoxalines [3]: we can obtain thiazoloquinoxaline 2a only if we boil xanthogenate 4a
for 4 h.
In the 1H NMR spectrum of thiazoloquinoxalines 2, 3, there is a diagnostic doublet signal [3-5] from the
H(9) proton of the azolo[a]quinoxalines, which resonates downfield (8.8-10.5 ppm), in contrast to other protons
of the aromatic rings.
3-Phenyl-1-thioxothiazolo[3,4-a]quinoxalin-4(5H)-one (2a). A. KOH (0.20 g, 3.6 mmol) and CS2
(0.9 ml) were dissolved in methyl alcohol (10 ml). Quinoxaline 1a (0.40 g, 1.5 mmol) was added to the solution
and it was boiled for 7 h. The precipitated crystals were filtered out and washed with methanol. Yield 30 mg
(6.5%).
B. A solution of compound 4a (0.60 g, 1.8 mmol) in AcOH (10 ml) was boiled for 4 h and allowed to
stand overnight. The precipitated crystals were filtered out and washed with 2-propanol. Yield 60 mg (11%).
C. A solution of compound 4a (0.30 g, 0.9 mmol) in CF3COOH (5 ml) was boiled for 40 min and
allowed to stand overnight. The precipitated crystals were filtered out and washed with 2-propanol. Yield 0.11 g
(40%); mp 300-302°C. IR spectrum (vaseline oil), ν, cm-1: 689, 738, 1075, 1130, 1165, 1224, 1398, 1489, 1606,
1
1687, 2500-3220. H NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 7.13-7.63 (8H, m, C6H5, H(6-8)); 10.48 (H, d,
J = 8.33, H(9)); 11.55 (1H, br. s, NH). Found, %: C 61.85; H 3.07; N 9.18; S 20.84. C16H10N2OS2. Calculated, %:
C 61.91; H 3.25; N 9.03; S 20.66.
3-Phenylthiazolo[3,4-a]quinoxaline-1,4(5H)-dione (3a). A solution of compound 4a (0.30 g,
0.9 mmol) in CF3COOH (5 ml) was boiled for 2 h. The precipitated crystals was filtered out and washed with
2-propanol. Yield 0.11 g (40.5%); mp 313-315°C (AcOH). The characteristics of 3a match those described in [3].
3-(2,4-Dichlorophenyl)thiazolo[3,4-a]quinoxaline-1,4(5H)-dione (3b). Obtained as for tricycle 3a
from quinoxaline 4b. Yield 41%; mp >360°C (DMSO). IR spectrum (vaseline oil), ν, cm-1: 478, 587, 756, 814,
1
842, 878, 1097, 1226, 1317, 1435, 1496, 1578, 1633, 1689, 2500-3220. H NMR spectrum (DMSO-d6), δ, ppm
(J, Hz): 7.16-7.24 (2H, m, H(6) or H(7), H(8)); 7.31 (1H, dd, J = 8.04, J = 6.68, H(6) or H(7)); 7.51 (1H, dd, J = 8.70,
J = 2.00, H(5) in C6H3Cl2); 7.59 (1H, d, J = 8.70, H(6)); 7.73 (1H, d, J = 2.00, H(3) in C6H3Cl2); 8.83 (1H, d,
J = 8.04, H(9)); 11.28 (1H, br. s, NH). Found, %: C 52.99; H 2.38; N 7.63; S 8.69; Cl 19.32. C16H8Cl2N2O2S.
Calculated, %: C 52.91; H 2.22; N 7.71; S 8.83; Cl 19.52.
3-(α-Methoxythiocarbonylthiobenzyl)quinoxalin-2(1H)-one (4a). KOH (0.40 g, 7.1 mmol) and CS2
(1.0 ml) were dissolved in methyl alcohol (30 ml) and then the mixture was stirred for 0.5 h. Quinoxaline 1a
(1.00 g, 3.7 mmol) was added to the solution and it was stirred for 4 h and allowed to standard overnight. The
crystals were filtered out and washed with 2-propanol. Yield 1.13 g (90%); mp 165-167°C (i-PrOH).
1
IR spectrum (vaseline oil), ν, cm-1: 698, 755, 1075, 1101, 1280, 1492, 1560, 1612, 1663, 2500-3220. H NMR
spectrum (DMSO-d6), δ, ppm (J, Hz): 4.14 (3H, s, CH3); 6.63 (1H, s, PhCH); 7.25-7.38 (5H, m); 7.55-7.65 (3H,
m); 7.84 (1H, d, J = 8.20, H(5)), 12.45 (1H, br. s, NH). Found, %: C 59.47; H 4.21; N 8.25; S 18.74.
C17H14N2O2S2. Calculated, %: C 59.63; H 4.12; N 8.18; S 18.72.
3-(α-Methoxythiocarbonylthio-2,4-dichlorobenzyl)quinoxalin-2(1H)-one (4b). Obtained as for
compound 4a from quinoxaline 1b. Yield 89%; mp 217-219°C (acetone). IR spectrum (vaseline oil), ν, cm-1:
1
469, 577, 749, 855, 891, 946, 1058, 1100, 1235, 1432, 1559, 1612, 1660, 2500-3220. H (DMSO-d6) NMR
spectrum, δ, ppm (J, Hz): 4.14 (3H, s, CH3); 6.93 (1H, s, ArCH); 7.28-7.39 (2H, m); 7.42 (1H, dd, J = 8.58,
J = 2.38, H(5) in C6H3Cl2); 7.52-7.62 (2H, m); 7.68 (1H, d, J = 2.38, H(3) in C6H3Cl2); 7.78 (1H, dd, J = 8.10,
J = 0.95, H(8)); 12.64 (1H, br. s, NH). Found, %: C 49.68; H 2.88; N 6.67; S 15.97; Cl 17.32. C17H12Cl2N2O2S2.
Calculated, %: C 49.64; H 2.94; N 6.81; S 15.59; Cl 17.24.
This work was done with the financial support of the Russian Foundation for Basic Research (grant
No. 03-03-32865).
130

REFERENCES
1.
2.
3.
C. Roussel, in: Thiazole and Its Derivatives (J. V. Metzger, ed.), Wiley, New York (1979), Pt. 2, p. 393.
V. A. Mamedov, I. A. Nuretdinov, and F. G. Sibgatullina, Izv. Akad. Nauk, Ser. Khim., 1412 (1988).
V. A. Mamedov, A. A. Kalinin, A. T. Gubaidullin, I. A. Litvinov, and Ya. A. Levin, Khim. Geterotsikl.
Soedin., 1664 (1999).
4.
5.
V. A. Mamedov, A. A. Kalinin, I. Kh. Rizvanov, N. M. Azancheev, Yu. Ya. Efremov, and Ya. A. Levin,
Khim. Geterotsikl. Soedin., 1279 (2002).
G. W. H. Cheeseman and B. Tuck, J. Chem. Soc. (C), 13, 1164 (1967).
ERRATUM
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The authors of the article "1H and C NMR Spectra of 9H-Pyrimido[4,5-b]indoles", Vol. 39, No. 10,
pp. 1348-1354, are V. P. Borovik, M. M. Shakirov, and O. P. Shkurko. The paper was presented of and on
behalf of N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry.
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