Synthesis of thiopyranochromen-2-ones, a new heterocyclic system

Full text of DOI:10.1007/s10593-011-0816-y

Chemistry of Heterocyclic Compounds, Vol. 47, No. 5, August 2011 (Russian original Vol. 47, No. 5, May, 2011)
SYNTHESIS OF THIOPYRANOCHROMEN-2-ONES,
A NEW HETEROCYCLIC SYSTEM
A. A. Shkel1*, O. A. Mazhukina1, and O. V. Fedotova1
Keywords: hydrogen sulfide, thiopyranochromen-2-ones, heterocyclization.
The reaction of 4-alkyl-4-hydroxychromen-2-ones with phosphorus pentasulfide leads to 2H-chro-
mene-2-thiones [1, 2]. We have shown that the reaction of 3-substituted 4-hydroxy-2H-chromen-2-ones with
hydrogen sulfide gives new condensed thiopyranochromene systems.
Thus, the action of hydrogen sulfide generated in situ from ZnS and HCl on 4-hydroxy-3-(3-oxo-
1,3-diphenylpropyl)-2H-chromen-2-one (1) in 3:1 acetic acid–acetic anhydride at 30°C gave 2,4-diphenyl-
4H-thiopyrano[3,2-c]chromen-5-one (3) in 70% yield. The reaction with chlorophenyl derivative 2 gave
2,4-di(4-chlorophenyl)-4H-pyrano[3,2-c]chromen-5-one (5) in 40% yield in addition to 2,4-di(4-chlorophenyl)-
4H-thiopyrano[3,2-c]chromen-5-one (4) obtained in 51% yield.
C6H4R
C6H4R
O
O
ZnS / HCl
O
O
C6H4R
C6H4R
C6H4R
O
O
O
O
OH
1, 2
C6H4R
O
O
O
+
C6H4R
O
S
C6H4R
5
3, 4
1, 3 R = H, 2, 4, 5 R = 4-Cl
_______________
*To whom correspondence should be addressed, e-mail: grigoryevaoa@mail.ru.
1
N. G. Chernyshevskii Saratov State University, Institute of Chemistry, 83 Astrakhanskaya Str., Saratov
410012 , Russia.
__________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 789–791, May, 2011. Original
article submitted March 29, 2011.
0009-3122/11/4705-0656©2011 Springer Science+Business Media, Inc.
656

HSQC heteronuclear correlation spectroscopy permitted assignment of the proton signals using cross
peaks: H-3 (H-3/C-3, 5.68–5.76/102–106 ppm) and H-4 (H-4/C-4, 4.57–4.66/34–36 ppm).
This reaction presumably proceeds initially through a mechanism featuring nucleophilic addition of
hydrogen sulfide at the most active carbonyl carbon atom of the aliphatic fragment in substrates 1 and 2 with
subsequent heterocyclization involving the thiol function and dehydration of cyclic sulfides to give compounds
3 and 4. This pathway has been reported for 1,5-dioxo compounds [3]. The electron-donor substituent in
compound 2 reduces the activity of the oxo group relative to nucleophilic attack, which leads to the competing
O-heterocyclization reaction giving pyranochromen-5-one 5.
O
C6H4R
C6H4R
O
O
H2S/H+
O

C6H4–R
OH
1, 2
C6H4R
O
O
O
:
SH
C6H4R
O
C6H4R
O
O
O
–2 H2O
C6H4R
S
C6H4R
S
OH
OH
3, 4
The IR spectra were taken on an FSM 1201 Fourier spectrometer for KBr pellets. The 1H NMR spectra
and HSBQ spectra were taken on a Varian 400 spectrometer at 400 MHz in CDCl3 at 25°C with TMS as the
internal standard.
4-Hydroxy-3-(3-oxo-1,3-diphenylpropyl)-2H-chromen-2-one (1) and 4-Hydroxy-3-[1,3-di(4-chloro-
phenyl)-3-oxopropyl]-2H-chromen-2-one (2). A mixture of 4-hydroxy-2H-chromen-2-one (1.0 g, 6.0 mmol)
and 1,3-diphenyl- (1.25 g, 6.0 mmol) or 1,3-di(4-chlorophenyl)-2-propen-1-one (1.45 g, 6.0 mmol) in ethanol
(30 ml) was stirred at reflux and maintained for 14 h. The crystalline precipitate was filtered off, washed with
ethanol, and dried to give 1.06 g (48%) 4-hydroxyoxopropylchromen-2-one 1; mp 152–153°C. IR spectrum, ,
1
cm–1: 1717 (C=O lact), 1689 (C=O), 3280 (OH). H NMR spectrum, , ppm, (J, Hz): 3.78 (1H, dd, J2a,3 = 2.0,
J2a,2b = 19.0, CH2); 4.47 (1H, dd, J2b,3 = 10.0, J2b,2a = 19.0, CH2); 4.94 (1H, dd, J3,2a = 2.0, J3,2b = 10.0, CH); 7.17–
8.08 (14H, m, Ar); 9.84 (1H, s, OH). Found, %: C 78.27; H 4.61%. C24H18O4. Calculated, %:
C 77.82; H 4.90%.
The yield of chromen-2-one 2 was 1.31 g (50%); mp 156–157°C. IR spectrum, , cm–1: 1720 (C=O
lact.), 1686 (C=O), 3320 (OH). 1H NMR spectrum, , ppm (J, Hz): 3.47 (1H, dd, J2a,3 = 3.0, J2a,2b = 18.0, CH2);
4.43 (1H, dd, J2b,3 = 11.0, J2b,2a = 18.0, CH2); 4.97 (1H, dd, 3,2a = 3.0, J3,2b = 11.0, CH); 7.76–8.03 (12H, m, Ar);
9.61 (1H, s, OH). Found, %: C 65.57; H 3.48; Cl 15.98. C24H16Cl2O4. Calculated, %: C 65.62; H 3.67; Cl 16.14.
2,4-Diphenyl-4H-thiopyrano[3,2-c]chromen-5-one (3). Acetic anhydride (10 ml) and glacial acetic
acid (20 ml) were added to a mixture of compound 1 (1.26 g, 3.4 mmol) and zinc sulfide (0.36 g, 4.1 mmol) and
stirred at 70–80°C until the reagents dissolved. The mixture was cooled and hydrochloric acid (6 ml, 19.6 mmol,
 = 1.19 g/ml) was added dropwise at 20–30°C to give 0.87 g (70%) thiopyranochromen-5-one 3; mp 131–
1
132°C. IR spectrum, , cm–1: 1650 (C=C), 1710 (C=O lact). H NMR spectrum, , ppm (J, Hz): 4.66 (1H, d,
J = 4.0, CH); 5.76 (1H, d, J = 4.0, HC=); 7.14–8.00 (14H, m, Ar). Found, %: C 78.09; H 4.35; S 8.76.
C24H16O2S. Calculated, %: C 78.24; H 4.38; S 8.70.
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2,4-Di-(4-chlorophenyl)-4H-thiopyrano[3,2-c]chromen-5-one (4) and 2,4-Di(4-chlorophenyl)-4H-
pyrano[3,2-c]chromen-5-one (5) were obtained analogously. The crystalline precipitate was filtered off to give
0.57 g (40%) of pyranochromenone 5; mp 120–121°C. IR spectrum, , cm–1: 1650 (C=C), 1705 (C=O lact.), 560
1
(C–Cl). H NMR spectrum, , ppm (J, Hz): 4.62 (1H, d, J = 4.0, CH); 5.75 (1H, d, J = 4.0 HC=); 7.24–7.98
(13H, m, Ar). Found, %: C 68.34; H 3.64; Cl 16.57. C24H14Cl2O3. Calculated, %: C 68.43; H 3.35; Cl 16.83.
The filtrate was treated with water. The precipitate was isolated to give 0.76 g (51%) thiopyrano-
1
chromen-5-one 4; mp 135–136°C. IR spectrum, , cm–1: 1645 (C=C), 1715 (C=O lact.), 565 (C–Cl). H NMR
spectrum, , ppm (J, Hz): 4.57 (1H, d, J = 4.0, CH); 5.68 (1H, d, J = 4.0, HC=); 7.11–8.00 (13H, m, Ar). Found,
%: C 65.66; H 3.60; Cl 15.98; S 7.58. C24H14Cl2O2S. Calculated, %: C 65.91; H 3.23; Cl 16.21; S 7.33.
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