SHORT PAPER
Preparation of Thioflavones
31
Table 1 Conversion of Various 1-(2-Hydroxyphenyl)-3-arylpro-
Column chromatography was performed using silica gel (Spectro-
chem 230–400 mesh) and TLC was carried out using Merck 25 DC-
Alufolien Kieselgel GF254 silica gel plates. Melting points were
obtained using a Scientific MP-DS melting point apparatus. IR
spectra were recorded on a Thermo Electron FTIR- 6700 spectrom-
pane-1,3-diones into Thioflavonesa
OH
O
O
O
R
PSCl3, H2O, Et3N
R
1
eter. H NMR (400 MHz) and 13C NMR (100 MHz) spectra were
S
obtained using a Bruker Avance DPX instrument with CDCl3 as the
solvent. Low-resolution electron impact (EI) mass spectra were re-
corded using an Agilent 5975C spectrometer. Elemental analyses
were obtained using an Elementar vario Micro cube instrument.
Entry
R
Time (min)b Yield (%)c Ref.
1
2
3
4
5
6
7d
8
9
Ph
90
90
88
83
81
83
78
82
69
94e
52
2c
2g
2e
2e
2c
2e
2h
2e
–
Thioflavones; General Procedure
4-ClC6H4
Et3N (5 mmol) was added slowly to a stirred mixture containing
H2O (5 mmol) and PSCl3 (5 mmol) at 30 °C. The resulting mixture
was heated at 60 °C for 5 min, the b-diketone (5 mmol) added, and
the mixture stirred at 80 °C for 15 min. At this point, cyclodehydra-
tion was complete and partial thionation of the flavone had also oc-
curred (TLC, hexane–EtOAc, 8:2). To complete the thionation
reaction, additional PSCl3 (5 mmol) and H2O (5 mmol) were added
followed by dropwise addition of Et3N (7.5 mmol), and heating was
continued at 80 °C. On completion of the reaction (indicated by
TLC), silica gel (ca. 1 g) was added and the mixture was purified by
silica gel column chromatography (hexane–EtOAc, 9:1) to afford
the expected thioflavone as a colored solid.
4-MeC6H4
90
4-FC6H4
90
4-MeOC6H4
4-O2NC6H4
3.4.5-(MeO)3C6H2
2,5-(O2N)2C6H3
2-thienyl
90
90
110
100
90
a Reactions were carried out under solvent-free conditions on 5 mmol
scale.
2-(Thiophen-2-yl)-4H-chromene-4-thione (Entry 9, Table 1)
Dark green crystals; mp 126–127 °C.
IR (KBr): 1598, 1553, 1506, 1420, 1382, 1170, 727 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.56 (dd, J1 = 1.6 Hz, J2 = 6.8 Hz,
1 H), 7.77 (dd, J1 = 1.2 Hz, J2 = 0.8 Hz, 1 H), 7.70–7.66 (m, 1 H),
7.63–7.61 (m, 2 H), 7.50 (d, J = 8.0 Hz, 1 H), 7.41–7.37 (m, 1 H),
7.23–7.17 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 201.31, 151.18, 150.40, 134.76,
134.05, 131.21, 129.79, 129.23, 128.90, 128.74, 126.21, 119.30,
118.21.
b Reactions were monitored by TLC (SiO2, hexane–EtOAc, 8:2).
c Yield of isolated product.
d Reaction facilitated by addition of MeNO2 (500 ml).
e Conversion determined by GC–MS.
bination was required and the reaction was continued at
the same temperature until complete.
The applicability of this protocol with other aryl-substitut-
ed 1,3-diketones was studied. After careful adjustments of
the reaction parameters, a range of 1,3-diketones with
functionalities such as halide, nitro, alkyl, alkoxy and
thienyl was found undergo this transformation (Table 1).
No significant difference in the reactivities of substrates
containing electron-donating or electron-withdrawing
groups was observed. However, the bulky substrate 1-(2-
hydroxyphenyl)-3-(3,4,5-trimethoxyphenyl)propane-1,3-
dione (entry 7, Table 1) required a longer reaction time,
with enhanced side product formation resulting in a lower
overall yield. A few drops of nitromethane were added to
this particular reaction in order to maintain efficient mix-
ing of the reagents. Only a moderate 52% yield of 2-
(thiophen-2-yl)-4H-chromene-4-thione (entry 9, Table 1)
was obtained. Further efforts to optimize the reaction con-
ditions for such substrates were not undertaken. All the
products gave satisfactory IR, NMR and mass spectral
data and were in accord with those reported in the litera-
ture.
MS (EI, 70 eV): m/z = 244 [M+], 200, 171, 126, 108, 100, 69.
Anal. Calcd for C13H8OS2: C, 63.90; H, 3.30; S, 26.25. Found: C,
64.04; H, 3.14; S, 26.33.
Acknowledgment
The authors thank Dr. R. Vijayaraghavan, Director, DRDE for his
keen interest and encouragement.
References
(1) (a) Razdan, R. K.; Bruni, R. J.; Mehta, A. C.; Weinhardt, K.
K.; Papanastassiou, Z. B. J. Med. Chem. 1978, 21, 643.
(b) Mughal, E. U.; Ayaz, M.; Hussain, Z.; Hasan, A.; Sadiq,
A.; Riaz, M.; Malik, A.; Hussain, S.; Choudhary, M. I.
Bioorg. Med. Chem. 2006, 14, 4704. (c) Ba, L. T.; Seth, M.
C. Chem. Commun. 2006, 203. (d) Dao, T. T.; Tuyen, T. N.;
Park, H. Arch. Pharm. Res. 2005, 28, 652.
(2) (a) Schonberg, A.; Nickel, S. Ber. Dtsch. Chem. Ges. 1931,
64, 2323. (b) Baker, W.; Harborne, J. B.; Ollis, W. J. Chem.
Soc. 1952, 1303. (c) Baker, W.; Clarke, G. G.; Harborne, J.
B. J. Chem. Soc. 1954, 998. (d) Levai, A. Heterocycl.
Commun. 1999, 5, 419. (e) Mughal, E. U.; Hasan, A.;
Rashid, L. Heterocycl. Commun. 2005, 11, 445. (f) Dudley,
K. H.; Miller, H.; Corley, R. C.; Wall, M. E. J. Med. Chem.
1967, 10, 985. (g) Witczak, Z.; Krolikowska, M. Pol. J.
Chem. 1981, 55, 763. (h) Briggs, M. T.; Duncan, G. L. S.;
Thornber, C. W. J. Chem. Res. 1982, 9, 2461.
In conclusion, we have developed a simple convenient
one-pot strategy for the preparation of thioflavones via cy-
clodehydration of b-diketones and subsequent thionation
of the intermediate flavones. The thiophosphoryl chlo-
ride–water–triethylamine (PSCl3–H2O–Et3N) reagent
system has been utilized as a dual purpose reagent for both
the cyclization and thionation steps.
Synthesis 2011, No. 1, 30–32 © Thieme Stuttgart · New York