A novel and simple synthesis of 2-(trifluoromethyl)-4H-thiochromen-4-ones

Article abstract of DOI:10.1080/10426500590912259

Alkyl 2-mercaptophenyl ketones react with trifluoroacetic anhydride in the presence of triethylamine to give 2-(trifluoromethyl)-4H-thiochromen-4-ones, which are transformed into the corresponding pyrazoles by treatment with hydrazine hydrate and into 1,1

Full text of DOI:10.1080/10426500590912259

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Phosphorus, Sulfur, and Silicon
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A Novel and Simple Synthesis
of 2-(Trifluoromethyl)-4H-
thiochromen-4-ones
Boris I. Usachev a , Vyacheslav Ya. Sosnovskikh a ,
Mikhail A. Shafeev a & Gerd-Volker Röschenthaler b
a Department of Chemistry , Ural State University ,
Ekaterinburg, Russia
b Institute of Inorganic & Physical Chemistry ,
University of Bremen , Bremen, Germany
Published online: 16 Aug 2006.
To cite this article: Boris I. Usachev , Vyacheslav Ya. Sosnovskikh , Mikhail A.
Shafeev & Gerd-Volker Röschenthaler (2005) A Novel and Simple Synthesis of 2-
(Trifluoromethyl)-4H-thiochromen-4-ones, Phosphorus, Sulfur, and Silicon and the
Related Elements, 180:5-6, 1315-1319, DOI: 10.1080/10426500590912259
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Phosphorus, Sulfur, and Silicon, 180:1315–1319, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500590912259
A Novel and Simple Synthesis of
2-(Trifluoromethyl)-4H-thiochromen-4-ones
Boris I. Usachev
Vyacheslav Ya. Sosnovskikh
Mikhail A. Shafeev
Department of Chemistry, Ural State University, Ekaterinburg, Russia
¨
Gerd-Volker Roschenthaler
Institute of Inorganic & Physical Chemistry, University of Bremen,
Bremen, Germany
Alkyl 2-mercaptophenyl ketones react with trifluoroacetic anhydride in the pres-
ence of triethylamine to give 2-(trifluoromethyl)-4H-thiochromen-4-ones, which are
transformed into the corresponding pyrazoles by treatment with hydrazine hydrate
and into 1,1-dioxides by oxidation with H O in AcOH.
2
2
Keywords 2-(Trifluoromethyl)-4H-thiochromen-4-one and their 1,1-dioxides; alkyl
2-mercaptophenyl ketones; pyrazoles
INTRODUCTION
Chromones are one of the most widely distributed classes of natu-
ral compounds occurring in the plant kingdom. Many natural and
synthetic chromone derivatives exhibit various types of biological
activities and are used as substrates in the preparation of a variety of
rearranged products and new heterocyclic systems.1,2 The widespread
occurrence of the chromone system in a variety of biologically active
products has stimulated considerable interest in the development of
new synthetic methods for the construction of chromones and their thio
Received July 9, 2004; accepted October 5, 2004.
This work was financially supported by the Deutsche Forschungsgemeinschaft (Grant
No. 436 RUS 113/758/1-1) and by the U.S. Civilian Research and Development Foundation
and Russian Federation Ministry of Education (Grants EK-005-X1 and Y1-005-04). We
are very grateful to T. Du¨lcks, Institute of Organic Chemistry, University of Bremen,
Germany, for recording the mass spectra.
Address correspondence to Vyacheslav Ya. Sosnovskikh, Department of Chemistry,
Ural State University, 620083 Ekaterinburg, Russia. E-mail: vyacheslav.sosnovskikh@
usu.ru
1315

1316
B. I. Usachev et al.
analogues.3–6 We report a facile, new procedure for the preparation of
2-trifluoromethyl- and 2-trifluoromethyl-3-propyl-1-thiochromones
from readily available alkyl 2-mercaptophenyl ketones.7
RESULTS AND DISCUSSION
The chemistry of the 1-thiochromones is well known.4−6 However, there
has been only one paper on the synthesis of 1-thiochromones with a
polyfluoroalkyl group at the 2 position.8 To the best of our knowledge,
no reports of the synthesis of 3-alkyl-2-polyfluoroalkyl-1-thiochromones
have appeared in the literature. In continuation of our studies on
the synthesis and chemical properties of 2-polyfluoroalkylchromones,
which turned out to be highly reactive compounds in the reactions with
N-, S-, and C-nucleophiles,2 we now report our results on the prepa-
ration and reactivity of 2-trifluoromethyl-1-thiochromones 1a,b. These
compounds were synthesized as shown in Scheme 1.
SCHEME 1
We found that the modified Baker–Venkataraman reaction of alkyl
2-mercaptophenyl ketones, prepared from thiosalicylic acid and the cor-
responding alkyllithium, with trifluoroacetic anhydride in the presence
of triethylamine in boiling THF, produced 1-thiochromones 1a,b, which
are of much interest because of their synthetic potential. Compounds
1a,b were smoothly oxidized by treatment with H2O2 in glacial acetic
acid and gave thiochromone 1,1-dioxides 2a,b in high yields. The re-
action of 1a with hydrazine hydrate at room temperature yields the
expected pyrazole 3 (Scheme 2).
SCHEME 2

Synthesis of 2-(Trifluoromethyl)-4H-thiochromen-4-ones
1317
In conclusion, the reaction of alkyl 2-mercaptophenyl ketones with
trifluoroacetic anhydride provides a simple process from readily avail-
able starting materials to 2-trifluoromethyl-1-thiochromones, which
may be considered as useful RF-containing substrates for the synthesis
of a wide variety of heterocyclic compounds with potential biological
activity.
EXPERIMENTAL
1H (200 or 400 MHz) and 19F (188 MHz) NMR spectra were recorded
on a Bruker DPS-200 and Bruker DRX-400 spectrometers in CDCl3
solution with TMS as the internal standard. Mass spectra were ob-
tained at 70 eV, 200◦C on a MAT 8200 spectrometer. The IR spec-
tra were measured on an IKS-29 instrument as suspensions in Nujol.
o-Mercaptoacetophenone was obtained from thiosalicylic acid and
methyllithium according to known method.7
1-(2-Sulfanylphenyl)pentan-1-one
A mixture of thiosalicylic acid (6.0 g, 0.039 mol) and finely dispersed LiH
(0.80 g, 0.10 mol) in anhydrous THF (20 ml) was refluxed for 0.5 h. Then
the mixture was cooled to rt and 100 ml of 1 M (0.10 mol) butyllithium in
Et2O was added under a nitrogen atmosphere. The mixture was allowed
to stand at rt for 4 h. It was then poured into water (100 ml), the aqueous
layer was saturated with ammonium chloride, and the organic phase
was separated. After removal of the solvent under reduced pressure,
the residual oil was distilled to give the fraction with bp 153–165◦C
(11 Torr). The crude product was treated with 15 ml of pentane at −30◦C
and the crystalline material was isolated by filtration to give the title
compound as colorless crystals. Yield 5.05 g (67%), mp 46–47◦C; IR
(Nujol) 1665 (C O), 1585, 1550 cm−1 (Ar); 1H NMR (400 MHz, CDCl3,
J/Hz) δ 0.95 (t, 3H, Me, J = 7.3), 1.41 (sext, 2H, CH2, J = 7.4), 1.73
(quint, 2H, CH2, J = 7.5), 2.97 (t, 2H, CH2, J = 7.4), 4.36 (s, 1H, SH),
7.18–7.22 (m, 1H, Ar), 7.29–7.32 (m, 2H, Ar), 7.88 (d, 1H, H-6, J = 7.8).
o
Anal. calcd. for C11H14OS: C, 68.00; H, 7.26. Found: C, 67.91; H, 7.17.
2-(Trifluoromethyl)-4H-thiochromen-4-one (1a)
Triethylamine (11.1 g, 0.11 mol) was added to a solution of
o-mercaptoacetophenone (4.0 g, 0.026 mol) and trifluoroacetic anhy-
dride (8.0 g, 0.038 mol) in anhydrous THF (15 ml). After the initial
exothermic reaction had subsided (approximately 10 min), the reac-
tion mixture was refluxed for 10 min. Then, diluted HCl (3 ml of water
and 9 ml of concentrated HCl) was added at heating and the resulting

1318
B. I. Usachev et al.
solution was refluxed for an additional 15 min. The cooled mixture was
quenched by addition of water (100 ml) and extracted with pentane (3 ×
20). After removal of the solvent under reduced pressure, the residual
oil was distilled to give the fraction with bp 90–95◦C (0.5 Torr). The
crude product was treated with 15 ml of 70% ethanol at −30◦C and
the crystalline material was isolated by filtration, washed with aque-
ous ethanol, and dried to give the title compound as colorless crystals.
Yield 2.65 g (44%), mp 52–53◦C (lit.8 mp 50–52◦C); MS m/z [Irel (%)]
230 [M]+ (89), 202 (100), 183 (34), 136 (61), 108 (44), 69 (29), 28 (50).
3-Propyl-2-(trifluoromethyl)-4H-thiochromen-4-one (1b)
This compound was obtained in a similar way to 1a in 23% yield as a
colorless solid; mp 73–74◦C; IR (Nujol) 1625 (C O), 1590, 1550 cm−1
(C C, Ar); 1H NMR (400 MHz, CDCl3, J/Hz) δ 1.04 (t, 3H, Me, J = 7.4),
5
1.51–1.61 (m, 2H, CH2), 2.83 (tq, 2H, CH2, J = 8.0, J = 1.7), 7.58
H,F
(ddd, 1H, H-6, J = 8.1, 6.7, J = 1.6), 7.62 (ddd, 1H, H-8, J = 8.1, J =
o
m
o
m
1.6, Jp = 0.6), 7.66 (ddd, 1H, H-7, J = 8.1, 6.7, J = 1.5), 8.50 (ddd, 1H,
o
m
H-5, J = 8.1, J = 1.5, Jp = 0.6). Anal. calcd. for C13H11F3OS: C, 57.34;
o
m
H, 4.07. Found: C, 57.63; H, 4.41.
2-(Trifluoromethyl)-1λ6-thiochromene-1,1,4-trione (2a)
A mixture of thiochromone 1a (0.50 g, 2.2 mmol), 33% H2O2 (3 ml), and
AcOH (6 ml) was heated in a water bath for 1 h and then cooled to room
temperature. The reaction mixture was diluted with water (20 ml) and
the crystalline product that precipitated was filtered off, washed with
water, dried, and recrystallized from methylcyclopentane. Yield 0.24 g
1
(42%) as a yellow powder; mp 135–136◦C; H NMR (200 MHz, CDCl3,
J/Hz) δ 7.08 (s, 1H, CH), 7.82 (td, 1H, H-6, J = 7.6, J = 1.2), 7.95 (td,
o
m
1H, H-7, J = 7.6, J = 1.3), 8.08 (dd, 1H, H-8, J = 7.9, J = 1.2), 8.19
o
m
o
m
(dd, 1H, H-5, J = 7.9, J = 1.3); 19F NMR (188 MHz, CDCl3, CFCl3)
o
δ −61.6 (d, CF3, 4 J =m1.0 Hz); MS m/z [Irel (%)] 262 [M]+ (20), 193
F,H
[M–CF3]+ (44), 136 (24), 104 (100), 76 (49), 50 (21); HRMS calcd. for
C10H5F3O3S (M+) 261.9912. Found: 261.9913.
3-Propyl-2-(trifluoromethyl)-1λ6-thiochromene-1,1,4-trione
(2b)
This compound was obtained in a similar way to 2a in 89% yield as a
colorless powder, mp 86–87◦C; 1H NMR (400 MHz, CDCl3, J/Hz) δ 1.04
(t, 3H, Me, J = 7.4), 1.56 (sext, 2H, CH2, J = 7.4), 2.74 (tq, 2H, CH2,
J = 8.0, 5 J = 1.5), 7.79 (td, 1H, H-6, J = 7.6, J = 1.2), 7.91 (td, 1H,
H,F
o
m

Synthesis of 2-(Trifluoromethyl)-4H-thiochromen-4-ones
1319
H-7, J = 7.6, J = 1.3), 8.06 (ddd, 1H, H-8, J = 7.9, J = 1.2, Jp =
o
m
o
m
0.4), 8.19 (ddd, 1H, H-5, J = 7.9, J = 1.3, Jp = 0.4); MS m/z [Irel (%)]
o
m
304 [M]+ (4), 171 (45), 104 (100), 76 (63); HRMS calcd. for C13H11F3O3S
(M+) 304.0381. Found: 304.0382.
3(5)-(2-Mercaptophenyl)-5(3)-trifluoromethylpyrazole (3)
A mixture of thiochromone 1a (0.20 g, 0.87 mmol) and 80% hydrazine
hydrate (0.5 ml) was stirred at room temperature for 20 min and then
20% HCl (7 ml) was added. The crystalline product that precipitated
was filtered off, washed with water, dried, and recrystallized from cy-
clohexane. Yield 0.13 g (62%) as yellow crystals; mp 92–94◦C; 1H NMR
(200 MHz, CDCl3) δ 3.62 (s, 1H, SH), 6.84 (s, 1H, CH), 7.27–7.54 (m,
4H, arom.), 11.3 (br.s, 1H, NH); 19F NMR (188 MHz, CDCl3, CFCl3)
δ −63.2 (s, CF3); MS m/z [Irel (%)] 244 [M]+ (100), 225 (14), 147 (39),
121 (17), 69 (14); HRMS calcd. for C10H7F3N2S (M+) 244.0282. Found:
244.0270.
REFERENCES
[1] G. P. Ellis, Chromenes, Chromanones, and Chromones, in The Chemistry of Hetero-
cyclic Compounds (Wiley: New York, 1977), Vol. 31.
[2] V. Ya. Sosnovskikh, Russ. Chem. Rev., 72, 489–516 (2003).
[3] C. Riva, C. De Toma, L. Donadel, C. Boi, R. Pennini, G. Motta, and A. Leonardi,
Synthesis, 195–201 (1994).
[4] T. Patonay, W. Adam, A. Le´vai, P. Ko¨ve´r, M. Ne´meth, E.-M. Peters, and K. Peters,
J. Org. Chem., 66, 2275–2280 (2001).
[5] A. Le´vai and Z. Szabo´, Bull. Soc. Chim. Fr., 128, 976–978 (1991).
[6] C. H. Chen, G. A. Reynolds, H. R. Luss, and J. H. Perlstein, J. Org. Chem., 51, 3282–
3289 (1986).
[7] M. Topolski, J. Org. Chem., 60, 5588–5594 (1995).
[8] K. Tamura, T. Ishihara, and H. Yamanaka, J. Fluorine Chem., 68, 25–31 (1994).