Synthesis of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]chromen-4-ones and 2-(trifluoromethyl)-4H-thieno[2,3-c]chromen-4-ones from 2-trifluoromethylchromones and ethyl mercaptoacetate

Article abstract of DOI:10.1016/S0040-4020(03)00329-6

The redox reaction of 2-trifluoromethylchromones with ethyl mercaptoacetate in the presence of triethylamine results in the formation of 1,2-dihydrothieno[2,3-c]chromen-4-ones and diethyl 3,4-dithiadipate in high yields. Oxidation of the first compounds w

Full text of DOI:10.1016/S0040-4020(03)00329-6

Tetrahedron 59 (2003) 2625–2630
Synthesis of 2-(trifluoromethyl)-1,2-dihydro-4H-thieno[2,3-c]
chromen-4-ones and 2-(trifluoromethyl)-4H-thieno[2,3-c]
chromen-4-ones from 2-trifluoromethylchromones and
ethyl mercaptoacetate
a,*
a
Vyacheslav Ya. Sosnovskikh, Boris I. Usachev, Dmitri V. Sevenard
b
b
and Gerd-Volker R o¨ schenthaler
a
Department of Chemistry, Ural State University, Lenina 51, 620083 Ekaterinburg, Russian Federation
Institute of Inorganic and Physical Chemistry, University of Bremen, Leobener Strasse, 28334 Bremen, Germany
b
Received 17 December 2002; revised 5 February 2003; accepted 28 February 2003
Abstract—The redox reaction of 2-trifluoromethylchromones with ethyl mercaptoacetate in the presence of triethylamine results in the
formation of 1,2-dihydrothieno[2,3-c]chromen-4-ones and diethyl 3,4-dithiadipate in high yields. Oxidation of the first compounds with
nitrogen dioxide gave 1,2-dihydrothieno[2,3-c]chromen-3,4-diones which were converted into thieno[2,3-c]chromen-4-ones. q 2003
Elsevier Science Ltd. All rights reserved.
1. Introduction
1
,2
It is known that the interaction of ethyl mercaptoacetate
with a,b-unsaturated ketones proceeds via nucleophilic
addition of the mercapto group to an activated CvC bond
with further cyclization at the carbonyl group leading to the
corresponding thiophene derivatives. A similar reaction of
alkyl mercaptoacetates with esters of 3-methoxy-4,4,4-
3
4
trifluorocrotonic, a-fluoroalkyl acetic and fluoroalkyl
5
propiolic acids gives alkyl 3-hydroxy-5-fluoroalkylthio-
6
phene-2-carboxylates, and with b-chloroenones and
4
a-fluoroalkyl ketones alkyl 5-fluoroalkylthiophene-2-car-
7
,8
boxylates are formed. o-Hydroxychalcones
can also
participate in this reaction, but owing to ortho-hydroxyl
group reaction is accompanied by tandem cyclization–
dehydration to 2-aryl-1,2-dihydro-4H-thieno[2,3-c]chromen-
Scheme 1.
participation of both electrophilic centers of dihydropyrones
without ring cleavage to give derivatives of 2-oxa-7-
thiabicyclo[3.2.1]octane 3 (Scheme 1).
4
is incorporated into the cycle, as in the case of cyclohex-2-
-ones (dihydrothienocoumarins) 1. When the double bond
9
enone, the mode of interaction with methyl mercapto-
acetate is changed and the initial product of a Michael
addition undergoes a spontaneous cyclization with con-
comitant loss of methoxide to afford the diketone 2, existing
2
. Results and discussion
1
0
in the enolic form. At the same time we have recently
In view of the unique biological properties displayed by
1
studied the reaction of 3,3-dialkyl-6-trifluoromethyl-2,3-
dihydro-4-pyrones with methyl and ethyl mercaptoacetates
and found that in this case, the reaction occurs with
1
many fluorinated heterocyclic compounds and as an
extension of our continuing synthetic studies concerning
1
2,13
the reactivity of 2-polyfluoroalkylchromones,
started investigations of the possible use of 2-trifluoro-
we have
3
Keywords: CF -containing chromones, coumarins, sulfur heterocycles;
1
4
methylchromones in the reaction with ethyl mercapto-
7
ethyl mercaptoacetate; redox reaction.
,8,10
*
0
Corresponding author. Tel.: þ7-3432-61-68-24; fax: þ7-3432-61-59-78;
acetate. Taking into account the results of previous work
it might be expected that this reaction would proceed
e-mail: Vyacheslav.sosnovskikh@usu.ru
040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00329-6

2626
V. Ya. Sosnovskikh et al. / Tetrahedron 59 (2003) 2625–2630
identified as the second product of this transformation.
These products can be viewed as resulting from a redox
reaction between chromones 6 and ethyl mercaptoacetate,
and no trace of an expected compounds 4 and 5 was
observed (Scheme 2).
The mechanism for the redox formation of coumarins 7 is
not obvious, but it is most likely that, as in the cases with
1
0
3
7
,3-dialkyl-6-trifluoromethyl-2,3-dihydro-4-pyrones and
1
6
-polyfluoroalkylnorkhellins, the reaction initially gives
benzo derivative of 2-oxa-7-thiabicyclo[3.2.1]octane 4,
which undergoes reductive ring-opening to ester 8 under
the action of ethyl mercaptoacetate. The latter compound is
oxidized to diethyl 3,4-dithiadipate and further two
intramolecular cyclizations of the intermediate ester 8
give dihydrothienocoumarins 7 (Scheme 2).
The substitutions on the phenyl ring did not effect the
synthetic results, but this reaction is typical only for
2
2
-trifluoromethylchromones and does not proceed with
-difluoromethyl-, 2-(1,1,2,2-tetrafluoroethyl)-, 2-trichloro-
methyl- and 2-methylchromones. The structures of the
coumarins 7 compare well with the results of elemental
1
13
19
analysis, H, C, F NMR and IR spectroscopy and mass
spectrometry. Furthermore, an X-ray diffraction analysis of
7
b was performed, proving the regiochemistry of the
1
5
1
reaction. The H NMR spectra of these compounds
showed signals for the aromatic protons and a characteristic
ABX-system ranging between 3.6–4.4 and 4.3–5.2 ppm for
the aliphatic protons of the CH2 and CH groups,
2
respectively; the coupling constants were JAB¼17.7–
Scheme 2.
3
3
1
9.2 Hz, J ¼10.3–12.3 Hz, and JBX¼2.6–4.5 Hz.
AX
either without opening of the pyrone ring to give benzo
derivatives of 2-oxa-7-thiabicyclo[3.2.1]octane 4 or with
ring opening. In the latter case, the reaction can be
accompanied by cyclization and dehydration stages to
yield thieno[2,3-c]coumarins 5 (Scheme 1).
The ready accessibility of dihydrothienocoumarins 7 have
made them useful substrates for constructing highly
functionalized biologically and medicinally important
products. Selective sulfur oxidation of these compounds to
sulfoxides or to sulfones is the more attractive route to
increase their reactivity. Indeed, we have recently
reported that the oxidation of compounds 7 in glacial
acetic acid containing an excess of aqueous hydrogen
peroxide (30%) selectively gives sulfones, 2-(trifluoro-
methyl)-1,2-dihydrothieno[2,3-c]chromen-3,3,4-triones,
which are transformed into 3-hydrazino-6-(2-hydroxyaryl)-
pyridazines under the action of hydrazine hydrate in
ethanol. This reaction is undoubtedly of interest since
7
,8
Here we describe our findings on the successful application
of this reaction to the preparation of trifluoromethyl-
containing coumarin derivatives (preliminary communi-
cation see Ref. 15). We found that the interaction of
1
7
2
a molar ratio of 1:3 at 808C in the presence of Et N as a
-trifluoromethylchromones 6 with ethyl mercaptoacetate in
3
catalyst afforded dihydrothienocoumarins 7a–k in 66–93%
yields. Also diethyl 3,4-dithiadipate was isolated and
Scheme 3.

V. Ya. Sosnovskikh et al. / Tetrahedron 59 (2003) 2625–2630
2627
measured on an IKS-29 instrument as suspensions in
vaseline oil. Mass spectra (electron impact, 70 eV) were
carried out on a MAT 8200 spectrometer. Elementary
analyses were performed at the Microanalysis Services of
the Institute of Organic Synthesis, Ural Branch, Russian
Academy of Sciences. Melting points are uncorrected. The
starting chromones 6 were prepared by condensation of the
appropriate 2-hydroxyacetophenones with ethyl trifluoro-
Scheme 4.
2
1
acetate according to described procedure. Assignment of
1
3
several derivatives of 3-hydrazinopyridazine exhibit
different types of biological activity as chemotherapeutics,
anti-inflammatory agents, CNS depressants and stimulants,
the signals in C NMR spectra was performed on the basis
2
2
of a gradient selected 2D HMBC spectrum and of data in
Ref. 23.
1
8
and anti-hypertensives (Scheme 3).
3
.1.1. Dihydrothienocoumarins 7a–k; general pro-
cedure. A mixture of chromone 6 (4.7 mmol), ethyl
mercaptoacetate (2.0 g, 17 mmol) and Et N (0.5 ml) with-
In this work, we were unable to selectively convert
dihydrothienocoumarins 7 to the corresponding sulfoxides
3
9
using a stoichiometric amount of the H O –AcOH system
2
out solvent was heated at 808C for 12 h. After cooling, the
reaction mixture was diluted with 5 ml of ethanol and the
crystalline material was isolated by filtration and washed
with ethanol to give 7 as a colourless or light yellow
crystals. After recrystallization from ethanol, the melting
point did not change.
2
and the use of well-known conventional oxidants such as
Na Cr O –H SO and ClO –CHCl , lead to complex
reaction mixtures. However, as representative examples,
we converted sulfides 7a,b to sulfoxides 9a,b in chloroform
with an excess of NO at room temperature over four days in
2
2
7
2
4
2
3
2
high yields and with quite complete chemoselectivity
1
(
characteristic AMX-system for the aliphatic protons of the
Scheme 3). The H NMR spectra of 9a,b showed a
The filtrate obtained after removal of 7a was distilled in
vacuo to give diethyl 3,4-dithiadipate, yield 43%, bp 135–
2
3
20
D
24
CH and CH groups with J ¼18.7 Hz, J ¼8.9 Hz, and
1408C (5 mmHg), n
¼1.4962 (lit., bp 112–1168C/
2
AM
AX
3
25
21
JMX¼3.6–3.7 Hz. It is worth mentioning that coumarin 7k
gave nitrosulfoxide 9k under the same conditions
Scheme 4).
0.3 mmHg, n
(400 MHz, CDCl
(2H, s, CH
S), 4.22 (2H, q, J¼7.1 Hz, CH
D
1.4950); nmax (neat) 1720 (CvO) cm
;
d
) 1.30 (3H, t, J¼7.1 Hz, Me), 3.58
H
3
(
2
2
O).
Note that sulfoxides 9a,b, in contrast to corresponding
sulfones did not react with hydrazine hydrate, but with 9a,b
in hand we were able to prepare thieno[2,3-c]coumarins
3.1.2. 2-(Trifluoromethyl)-1,2-dihydro-4H-thieno
[2,3-c]chromen-4-one (7a). Yield 85%, mp 146–1478C;
(Found: C, 52.84; H, 2.64. C12H F O S requires C, 52.94;
7 3 2
H, 2.59%); nmax 1720 (CvO), 1610, 1560w (CvC,
5
a,b using the Pummerer rearrangement followed by
arom.) cm2 ; d
1
(250.1 MHz, CDCl
¼3.78, d
BX¼4.5 Hz, CH
) 3.66–3.85 (2H,
aromatization. Thus, heating for a short time (1–2 min) of
sulfoxides 9a,b with acetic anhydride in the presence of a
catalytic amounts of H SO cleanly afforded thieno[2,3-c]
H
3
2
AB-part of ABX-system, d
¼3.73,
), 4.37–4.53
(1H, m, CH), 7.28–7.40 (3H, m, H , H , H ), 7.51 (1H, ddd,
J
AB
¼
A
B
3
3
18.3 Hz,
J
AX¼10.3 Hz,
J
2
4
2
1
6
8
9
coumarins 5a,b in 84–90% yields. The H NMR spectrum
of 5a in CDCl displayed no signals for CH and CH
7
JH7;H6¼8.6 Hz, JH7;H8¼6.9 Hz, JH7;H9¼2.0 Hz, H ); d
3
2
C
4
3
protons; however, a quartet at d 7.96 with JH,F¼0.9 Hz
(50.3 MHz, CDCl
3
) 35.72 (q, JC,F¼2.3 Hz, CH
2
), 47.80
),
44.97 (vC–S), 152.95 (vC–O), 156.08 (CvO), 116.92,
2
1
assigned to the thiophene proton was observed.
(q, JC,F¼31.6 Hz, CH), 125.54 (q, JC,F¼277.8 Hz, CF
3
1
In conclusion, the reaction of 2-trifluoromethylchromones
with ethyl mercaptoacetate provides a simple and con-
venient one-pot process from the readily available starting
117.43, 123.92, 124.93, 126.34, 130.86; d
3
F
(188.3 MHz,
); MS (70 eV,
CDCl
, CFCl
2008C), m/z (Irel (%)): 272 [M] (100), 253 [M2F] (3),
) 275.28 (d, JF,H¼8.6 Hz, CF
3
3
3
þ
þ
þ
þ
materials to CF -containing 1,2-dihydrothieno[2,3-c]chro-
3
244 [M2CO] (3), 203 [M2CF
3
]
(23), 175 [M2CO–
þ
(45), 115 [HSvCH–
þ
þ
men-4-ones 7 in high yields, which are expected to be
1
biologically active and can be used as optical brightening
CF
CF
3
3
]
(3), 159 [M2CO
þ
2
–CF
3
]
9
þ
þ
] (41), 69 [CF
] (4), 45 [HC;S] (5), 28 [CO] (15).
3
2
0
agents, dispersed fluorescent and laser dyes. Moreover,
these compounds are useful substrates for constructing
biologically and medicinally important products.
3.1.3. 8-Methyl-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7b). Yield 79%, mp 181–
1
5
828C; (Found: C, 54.36; H, 3.15. C H F O S requires C,
13 9 3 2
4.54; H, 3.17%); n
1
1710 (CvO), 1610, 1570 (CvC,
max
2
3
. Experimental
arom.) cm ; d (250.1 MHz, CDCl ) 2.42 (3H, s, Me),
H 3
2
3
J
.65–3.84 (2H, ABX, d ¼3.76, d ¼3.72, J ¼18.4 Hz,
A
B
AB
3
3
3
.1. General
AX¼11.0 Hz,
J
BX¼3.8 Hz, CH
2
), 4.36–4.52 (1H, m,
9
o
6
CH), 7.13 (1H, br s, H ), 7.25 (1H, d, J¼8.3 Hz, H ), 7.31
1
o
m
7
H NMR spectra were recorded on a Bruker WM-250 and
Bruker DRX-400 spectrometers operating at 250.13 or at
(1H, dd, J¼8.3 Hz, J¼1.7 Hz, H ); d
CDCl 20.85 (Me), 35.75 (CH ), 47.80 (q,
C,F¼277.9 Hz, CF ),
144.89 (vC–S), 151.20 (vC–O), 156.30 (CvO),
116.68, 117.21, 123.75, 126.22, 131.86, 134.76; d
C
(90.6 MHz,
)
3
2
2
1
4
00.13 MHz in CDCl or DMSO-d solutions with TMS as
3
J
C,F¼31.7 Hz, CH), 125.58 (q,
J
3
6
13
1
9
the internal standard. F and C NMR spectra were
recorded on a Bruker DPS-200 spectrometer operating at
F
3
1
88.3 and 50.3 MHz, respectively. IR spectra were
(188.3 MHz, CDCl
3
, CFCl
3
) 275.30 (d,
J
F,H¼8.6 Hz,

2628
V. Ya. Sosnovskikh et al. / Tetrahedron 59 (2003) 2625–2630
þ
CF ); MS (70 eV, 2008C), m/z (I (%)): 286 [M] (100),
3
130.58; dF (188.3 MHz, DMSO-d , CFCl ) 274.40 (d,
6 3
rel
þ
89 [M2CO–CF ] (4), 173 [M2CO –CF ] (27), 115
þ
þ
3
2
1
[
67 [M2F] (2), 258 [M2CO] (4), 217 [M2CF ] (16),
3
JF,H¼8.6 Hz, CF ); MS (70 eV, 2008C), m/z (I (%)): 306
3
rel
þ
þ
þ
þ
þ
[M2CO –CF ] (18), 158 [M2CO –CF –Cl] (15), 69
þ
[M] (100), 278 [M2CO] (4), 237 [M2CF ] (20), 193
3
3
2
3
þ
þ
þ
þ
HSvCH–CF ] (7), 69 [CF ] (3), 45 [HC;S] (4), 28
3
3
2
3
2
3
þ
þ
þ
þ
[
CO] (13).
[CF ] (6), 45 [HC;S] (4), 28 [CO] (15).
3
3
.1.4. 8-Methoxy-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7c). Yield 93%, mp 185–
868C; (Found: C, 51.60; H, 2.97. C H F O S requires C,
13 9 3 3
3.1.8. 8-Bromo-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7g). Yield 83%, mp 196–
1978C; (Found: C, 41.14; H, 1.69. C H BrF O S requires
1
5
12
6
3 2
1.66; H, 3.00%); n
1
1710 (CvO), 1620, 1570 (CvC,
C, 41.05; H, 1.72%); n
21
1710 (CvO), 1600, 1550 (CvC,
max
max
2
arom.) cm ; dH (250.1 MHz, CDCl ) 3.63–3.83 (2H,
3
arom.) cm ; dH (250.1 MHz, CDCl ) 3.63–3.83 (2H,
3
2
3
2
3
ABX, d ¼3.76, d ¼3.70, J ¼18.3 Hz, J ¼10.7 Hz,
ABX, d ¼3.75, d ¼3.70, J ¼18.3 Hz, J ¼11.1 Hz,
A
B
AB
AX
A
B
AB
AX
3
3
o
o
J
¼4.5 Hz, CH ), 3.86 (3H, s, MeO), 4.37–4.52 (1H, m,
J
¼3.8 Hz, CH ), 4.38–4.54 (1H, m, CH), 7.26 (1H, d,
BX
2
m
BX
2
9
o
6
m
9
CH), 6.75 (1H, d, J¼2.8 Hz, H ), 7.06 (1H, dd, J¼9.1 Hz,
J¼8.8 Hz, H ), 7.47 (1H, d, J¼2.0 Hz, H ), 7.58 (1H, dd,
m
7
o
6
m
7
J¼2.8 Hz, H ), 7.30 (1H, d, J¼9.1 Hz, H ); d
J¼8.8 Hz, J¼2.0 Hz, H ).
C
(90.6 MHz, DMSO-d þCDCl ) 35.32 (CH ), 46.89 (q,
2
J J
C,F C,F
6
3
2
1
¼31.2 Hz, CH), 55.32 (MeO), 125.32 (q,
¼
3.1.9. 6,8-Dibromo-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7h). Yield 69%, mp 194–
1968C; (Found: C, 33.56; H, 0.86. C H Br F O S requires
2
1
77.7 Hz, CF ), 106.41, 117.05, 117.33, 117.91, 125.40,
3
45.20, 146.67, 155.47, 155.76; d (188.3 MHz, DMSO-
F
12
5
2 3 2
3
d þCDCl , CFCl ) 274.90 (d, J ¼8.6 Hz, CF ); MS
C, 33.52; H, 1.17%); n
21
1725 (CvO), 1615, 1545 (CvC,
max
6
3
3
F,H
3
þ
2), 274 [M2CO] (22), 272 [M2CH O] (100), 259
þ
(
(
[
70 eV, 2008C), m/z (I (%)): 302 [M] (87), 283 [M2F]
rel
arom.) cm ; dH (400.1 MHz, DMSO-d ) 3.89–4.03 (2H,
6
þ
M2CO–CH ] (8), 233 [M2CF ] (23), 205 [M2CO–
þ
2
3
ABX, d ¼3.99, d ¼3.94, JAB¼19.2 Hz, JAX¼3.4 Hz,
2
A
B
þ
þ
3
J
¼10.9 Hz, CH ), 5.11–5.21 (1H, m, CH), 7.99 (1H, d,
3
3
BX
2
þ
þ
þ
(8), 159 [M2CH O–CO –CF ]
m
9
m
7
CF3] (5), 203 [M2CH O–CF ] (16), 189 [M2CO –
2
J¼2.2 Hz, H ), 8.12 (1H, d, J¼2.2 Hz, H ).
3
2
þ
CF3]
[
(35), 115
þ
2
2
3
þ
þ
HSvCH–CF ] (29), 69 [CF3] (6), 45 [HC;S] (4),
3.1.10. 7,9-Dimethyl-2-(trifluoromethyl)-1,2-dihydro-
4H-thieno[2,3-c]chromen-4-one (7i). Yield 89%, mp
3
þ
2
8 [CO] (46).
165–1668C; (Found: C, 56.26; H, 3.74. C H F O S
requires C, 56.00; H, 3.69%); n
1600 (CvC, arom.) cm ; dH (250.1 MHz, CDCl ) 2.37
3
14 11 3 2
3.1.5. 7-Methoxy-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7d). Yield 91%, mp 172–
1720 (CvO), 1620,
max
2
1
7
9
1
738C; (Found: C, 51.62; H, 2.93. C H F O S requires C,
3 9 3 3
(3H, s, Me ), 2.61 (3H, s, Me ), 3.89–4.04 (2H, ABX,
2
1
3
5
(
1.66; H, 3.00%); n
1
1710 (CvO), 1620, 1605, 1550
CvC, arom.) cm ; dH (250.1 MHz, CDCl ) 3.61–3.81
d ¼4.01, d ¼3.95,
JAB¼18.2 Hz,
JAX¼11.3 Hz,
max
A
B
2
3
J
¼3.6 Hz, CH ), 4.29–4.45 (1H, m, CH), 6.90 (1H, s,
3
BX
2
2
8
6
(2H,
3
ABX,
d ¼3.73,
d ¼3.67,
JAB¼18.3 Hz,
H ), 7.02 (1H, s, H ); d (90.6 MHz, CDCl ) 21.28 (Me),
C
A
B
3
3
2
JAX¼10.4 Hz, J ¼4.2 Hz, CH ), 3.87 (3H, s, MeO),
22.83 (Me), 39.85 (CH ), 47.36 (q, J ¼31.2 Hz, CH),
BX
2
2
C,F
6
1
4
.34–4.50 (1H, m, CH), 6.86 (1H, br s, H ), 6.88 (1H, dd,
125.64 (q, J ¼278.1 Hz, CF ), 144.82 (vC–S), 154.21
C,F 3
o
m
8
o
J¼8.1 Hz, J¼2.4 Hz, H ), 7.25 (1H, dd, J¼8.1 Hz,
(vC–O), 156.27 (CvO), 115.07, 115.92, 125.68, 129.25,
133.86, 141.25; d (188.3 MHz, CDCl , CFCl ) 275.42 (d,
p
9
J¼0.7 Hz, H ).
F
3
3
3
JF,H¼8.6 Hz, CF ); MS (70 eV, 2008C), m/z (I (%)): 300
þ þ þ
[M] (100), 281 [M2F] (3), 272 [M2CO] (5), 231
[M2CF ] (24), 203 [M2CO–CF ] (13), 187 [M2CO –
3
(58), 172 [M2CO –CF –CH ]
2
[HSvCH–CF ] (15), 69 [CF3] (5), 45 [HC;S] (5),
28 [CO] (9).
3
rel
3
.1.6. 8-Amino-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7e). Yield 72%, mp 202–
048C; (Found: C, 50.06; H, 2.67; N, 4.90. C H F NO S
þ
þ
3
2
þ
þ
2
CF3]
(20), 115
þ
1
2
8
3
2
3
3
þ
þ
requires C, 50.18; H, 2.81; N, 4.88%); nmax 3390 (NH ),
2
3
2
1
þ
1
(
3
710 (CvO), 1630, 1570 (CvC, arom.) cm ; dH
2
400.1 MHz, DMSO-d ) 3.66 (1H, dd, J¼18.7 Hz,
6
2
3
J¼3.5 Hz, CHH), 3.93 (1H, dd, J¼18.7 Hz, J¼10.6 Hz,
3.1.11. 2-(Trifluoromethyl)-2,3-dihydro-11H-benzo-
[h]thieno[2,3-c]chromen-11-one (7j).
3
3
3
CHH), 5.06 (1H, quint d,
3
J
¼ J ¼9.0 Hz,
J
¼
H,H
H,F
H,H
m
.4 Hz, CH), 5.30 (2H, s, NH ), 6.68 (1H, d, J¼2.6 Hz,
2
9
o
m
7
H ), 6.84 (1H, dd, J¼8.9 Hz, J¼2.6 Hz, H ), 7.18 (1H, d,
o
6
J¼8.9 Hz, H ).
3.1.7. 8-Chloro-2-(trifluoromethyl)-1,2-dihydro-4H-
thieno[2,3-c]chromen-4-one (7f). Yield 80%, mp 181–
1
C, 47.00; H, 1.97%); n
828C; (Found: C, 47.15; H, 1.79. C H ClF O S requires
12 6 3 2
1710 (CvO), 1610, 1565 (CvC,
max
arom.) cm2 ; dH (400.1 MHz, CDCl ) 3.67–3.81 (2H,
1
3
Yield 74%, mp 212–2138C; (Found: C, 59.93; H, 2.87.
C H F O S requires C, 59.63; H, 2.81%); n
2
3
ABX, d ¼3.76, d ¼3.70, J ¼18.2 Hz, J ¼10.9 Hz,
1715
max
A
B
AB
AX
16
9
3
2
3
o
o
21
J
¼4.3 Hz, CH ), 4.41–4.51 (1H, m, CH), 7.32 (1H, d,
(CvO), 1630w, 1600, 1560w, 1510w (CvC, arom.) cm
;
BX
2
6
m
9
J¼8.9 Hz, H ), 7.33 (1H, d, J¼2.4 Hz, H ), 7.45 (1H, dd,
dH (250.1 MHz, CDCl ) 3.74–3.89 (2H, ABX, d ¼3.83,
3
A
m
7
2
3
3
J¼8.9 Hz, J¼2.4 Hz, H ); d (90.6 MHz, DMSO-d )
d ¼3.78,
J
¼18.4 Hz,
J
¼2.7 Hz,
J
BX
¼12.3 Hz,
C
6
B
AB
AX
2
o
3
1
5.43 (CH ), 46.83 (q, J ¼30.5 Hz, CH), 126.10 (q,
CH ), 4.39–4.55 (1H, m, CH), 7.31 (1H, d, J¼8.5 Hz,
2
C,F
2
5
7
8
o
JC,F¼277.5 Hz, CF ), 145.99 (vC–S), 151.04 (vC–O),
H ), 7.58–7.65 (2H, m, H , H ), 7.68 (1H, d, J¼8.5 Hz,
H ), 7.82–7.86 (1H, m, H ), 8.45–8.49 (1H, m, H ); d
C
3
4
6
9
1
55.25 (CvO), 118.24, 118.54, 124.59, 125.96, 128.93,

V. Ya. Sosnovskikh et al. / Tetrahedron 59 (2003) 2625–2630
2629
3
(
50.3 MHz, CDCl ) 36.04 (q, J ¼2.0 Hz, CH ), 47.98 (q,
requires C, 51.66; H, 3.00%); n 1710 (CvO), 1620,
max
3
C,F
2
2
1
21
JC,F¼31.7 Hz, CH), 125.61 (q,
J
C,F
¼278.2 Hz, CF ),
1565 (CvC, arom.) cm ; d (400.1 MHz, CDCl ) 2.47
H 3
3
2
3
1
1
1
2
(
[
46.05 (vC–S), 149.95 (vC–O), 156.12 (CvO),
13.00, 119.89, 122.24, 122.98, 125.14, 125.65, 127.58,
27.87, 128.49, 134.12; d (188.3 MHz, CDCl , CFCl )
(3H, s, Me), 3.65 (1H, dd, J¼18.7 Hz, J¼3.6 Hz, CHH),
3
3
H,H H,F H,H
3
4.08 (1H, quint d, J ¼ J ¼9.2 Hz, J ¼3.6 Hz, CH),
2
3
4.21 (1H, dd, J¼18.7 Hz, J¼8.9 Hz, CHH), 7.36 (1H, d,
F
3
3
3
o
6
m
9
75.21 (d, J ¼8.6 Hz, CF ); MS (70 eV, 2008C), m/z
J¼8.5 Hz, H ), 7.39 (1H, d, J¼0.9 Hz, H ), 7.55 (1H, dd,
F,H
3
þ
þ
M2CF ] (5), 225 [M2CO–CF ] (5), 209 [M2CO2–
o
m
7
Irel (%)): 322 [M] (74), 294 [M2CO] (11), 253
J¼8.5 Hz, J¼1.9 Hz, H ).
þ
þ
3
3
þ
þ
þ
þ
4
CF ] (9), 115 [HSvCH–CF ] (18), 86 (100), 69 [CF ]
3
3.2.3. 6-Nitro-2-(trifluoromethyl)-1,2-dihydro-3l -ben-
zo[ f]thieno[2,3-c]chromen-3,4-dione (9k). Yield 52%,
mp 210–2128C; (Found: C, 50.04; H, 2.10; N, 3.32.
C H F NO S requires C, 50.14; H, 2.10; N, 3.65%); n
max
3
3
þ
(
9), 45 [HC;S] (6), 28 [CO] (66).
3.1.12. 2-(Trifluoromethyl)-1,2-dihydro-4H-benzo[ f]th-
ieno[2,3-c]chromen-4-one (7k).
1
6
8
3
5
1725 (CvO), 1620, 1580, 1515 (CvC, arom.), 1545
(NO ) cm ; dH (400.1 MHz, DMSO-d ) 4.34 (1H, m,
2
2 6
1
o
CHH), 4.93 (2H, m, CHH, CH), 7.90 (1H, ddd, J¼8.2,
m
9
10
o
7
7
.0 Hz, J¼0.9 Hz, H or H ), 7.99 (1H, ddd, J¼8.5,
m
10
9
o
.0 Hz, J¼1.4 Hz, H or H ), 8.18 (1H, dd, J¼8.5 Hz,
m
8
7
o
J¼1.2 Hz, H ), 8.51 (1H, s, H ), 8.71 (1H, d, J¼8.7 Hz,
1
1
H ).
Yield 66%, mp 228–2298C; (Found: C, 59.37; H, 2.88.
C H F O S requires C, 59.63; H, 2.81%); n 1720
max
3.3. Thienocoumarins 5a,b; general procedure
1
6
9
3
2
(
arom.) cm ; dH (250.1 MHz, CDCl ) 4.23–4.38 (2H,
CvO), 1620w, 1600w, 1580w, 1540w, 1515w (CvC,
2
A mixture of sulfoxide 9 (3.0 mmol), Ac
drop of conc. H SO was refluxed for 1–2 min, the reaction
was cooled, and the solid residue was isolated by filtration,
washed with AcOH (100 ml), and dried.
O (3 ml) and 1
2
1
3
2
4
2
3
ABX, d ¼4.31, d ¼4.26, JAB¼17.7 Hz, JAX¼2.6 Hz,
A
B
3
o
o
J
¼11.9 Hz, CH ), 4.43–4.59 (1H, m, CH), 7.47 (1H, d,
BX
2
6
o
9
J¼9.1 Hz, H ), 7.58 (1H, t, J¼7.5 Hz, H ), 7.68 (1H, td,
m
10
o
7
J¼7.7 Hz, J¼1.2 Hz, H ), 7.92 (2H, d, J¼8.7 Hz, H ,
3.3.1. 2-(Trifluoromethyl)-4H-thieno[2,3-c]chromen-4-
one (5a). Yield 84%, mp 169–1708C; (Found: C, 53.23;
H, 1.83. C12H F O S requires C, 53.34; H, 1.87%); nmax
5 3 2
8
o
11
H ), 8.24 (1H, d, J¼8.5 Hz, H ); d (50.3 MHz, CDCl )
C
3
3
2
4
0.81 (q, J ¼2.0 Hz, CH ), 47.75 (q, J ¼31.4 Hz,
C,F
2
C,F
1
CH), 125.60 (q, J ¼278.2 Hz, CF ), 144.63 (vC–S),
3105 (vCH), 1725 (CvO), 1625, 1605w, 1560w (CvC,
2
C,F
3
1
o
1
1
53.31 (vC–O), 156.04 (CvO), 113.08, 117.44, 123.80,
25.94, 127.39, 128.11, 128.61, 129.73, 131.22, 132.45; dF
arom.) cm ; d
m
H
(250 MHz, CDCl
8
3
) 7.39 (1H, ddd, J¼7.8,
o
m
7.2 Hz, J¼1.2, H ), 7.47 (1H, dd, J¼8.4 Hz, J¼1.0 Hz,
3
6
o
m
7
(188.3 MHz, CDCl , CFCl ) 275.33 (d, JF,H¼8.6 Hz,
CF ); MS (70 eV, 2008C), m/z (I (%)): 322 [M] (100),
94 [M2CO] (5), 253 [M2CF ] (42), 225 [M2CO–
þ
CF ] (6), 209 [M2CO –CF ] (7), 115 [HSvCH–CF ]
3
H ), 7.56 (1H, ddd, J¼8.4, 7.2 Hz, J¼1.6 Hz, H ), 7.83
3
3
þ
o
m
9
(1H, dd, J¼7.8 Hz, J¼1.2 Hz, H ), 7.96 (1H, q,
3
rel
þ
þ
4
1
2
J
H,F¼0.9 Hz, H ).
3
þ
þ
3
2
3
þ
þ
þ
(
5), 86 (64), 69 [CF ] (8), 45 [HC;S] (3), 28 [CO] (29).
3.3.2. 8-Methyl-2-(trifluoromethyl)-4H-thieno[2,3-c]
chromen-4-one (5b). Yield 90%, mp 247–2488C;
3
3
.2. Sulfoxides 9a,b,k; general procedure
(Found: C, 54.84; H, 2.41. C13
H, 2.48%); n 3135, 3105 (vCH), 1725 (CvO), 1620w,
H F O S requires C, 54.93;
7 3 2
max
1590w, 1555w (CvC, arom.) cm2 ; d
1
(400 MHz, DMSO-
7
A solution of dihydrothienocoumarin 7 (3.0 mmol) in
chloroform (10 ml) saturated by NO was kept at room
temperature for four days. After evaporation of CHCl the
3
residue was diluted with water (20 ml) and the crystalline
materials was isolated by filtration, washed with water
H
6
d
6
dq,
4
) 2.43 (3H, s, Me), 7.44–7.49 (2H, m, H , H ), 8.13 (1H,
m
2
4
9
J¼2.1 Hz,
J
H,Me¼0.6 Hz, H ), 8.80 (1H, q,
1
J
H,F¼1.0 Hz, H ).
(
100 ml), dried, and recrystallized from toluene.
Acknowledgements
4
3.2.1. 2-(Trifluoromethyl)-1,2-dihydro-3l -thieno[2,3-c]
chromen-3,4-dione (9a). Yield 85%, mp 208–2098C;
This work was financially supported by the Russian
Foundation for Basic Research (grant N 02-03-32706)
and, in part, by the US Civilian Research and Development
Foundation (grant REC-005). Dr T. D u¨ lcks, Institute of
Organic Chemistry, University of Bremen, Germany, is
thanked for recording the mass spectra.
(
H, 2.45%); n
Found: C, 50.18; H, 2.32. C H F O S requires C, 50.00;
12 7 3 3
1725 (CvO), 1620, 1570 (CvC,
arom.) cm ; d (400.1 MHz, CDCl ) 3.67 (1H, dd,
max
2
1
H
3
2
3
3
3
J¼18.7 Hz, J¼3.7 Hz, CHH), 4.10 (1H, quint d, J
¼
H,H
3
J
2
¼9.2 Hz,
J
¼3.7 Hz, CH), 4.24 (1H, dd,
H,F
H,H
3
o
J¼18.7 Hz, J¼8.9 Hz, CHH), 7.45 (1H, ddd, J¼7.4,
m
8
o
6
8
(
7
.0 Hz, J¼1.0 Hz, H ), 7.47 (1H, d, J¼8.5 Hz, H ), 7.63
o
m
9
o
1H, dd, J¼7.9 Hz, J¼1.5 Hz, H ), 7.76 (1H, ddd, J¼8.6,
m
7
.4 Hz, J¼1.6 Hz, H ).
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4
3
.2.2. 8-Methyl-2-(trifluoromethyl)-1,2-dihydro-3l -
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1
1
3 9 3 3

2630
V. Ya. Sosnovskikh et al. / Tetrahedron 59 (2003) 2625–2630
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