An easy approach to the synthesis of new fused 3-aryl-5- trifluoromethyl-7,8-dihydro-6H-thieno [2,1-f] [1,2] thiazine 1-oxide system

Article abstract of DOI:10.2174/157017809787582726

A new series of 4-alkyl(aryl)-4-tetramethylenesulfoximide-1,1,1- trifluoroalk-3-en-2-ones has been prepared from the O,N-exchange reactions of 4-alkyl(aryl)-4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones with the cyclic S,Stetramethylenesulfoximide in absence of

Full text of DOI:10.2174/157017809787582726

Letters in Organic Chemistry, 2009, 6, 145-150
145
An Easy Approach to the Synthesis of New Fused 3-Aryl-5-
trifluoromethyl-7,8-dihydro-6H-thieno [2,1-f] [1,2] thiazine 1-Oxide Sys-
tem
Helio G. Bonacorso*, Renata P. Vezzosi, Roberta L. Drekener, Nilo Zanatta and Marcos A. P.
Martins
Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria,
97105-900 Santa Maria, RS, Brazil
Received March 18, 2008: Revised December 10, 2008: Accepted December 11, 2008
Abstract: A new series of 4-alkyl(aryl)-4-tetramethylenesulfoximide-1,1,1-trifluoroalk-3-en-2-ones has been prepared
from the O,N-exchange reactions of 4-alkyl(aryl)-4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones with the cyclic S,S-
tetramethylenesulfoximide in absence of solvent, in good yields. Subsequently, the easy preparation of a new series of a
fused heterocyclic system of 3-aryl-5-trifluoromethyl-7,8-dihydro-6H-thieno[2,1-f][1,2]thiazine 1-oxide derivatives (60-
85% yields) from intramolecular cyclization reactions of sulfoximide enones employing potassium t-butoxide in diethyl
ether at reflux is also reported.
Keywords: Sulfoximides, trifluoromethyl ketones, 1,2-thiazines, enaminoketones.
1. INTRODUCTION
nitrogen [7-11] or in sodium methoxide/ethanol [12] with
low yields in both cases.
Piroxicam, an N-heterocyclic carboxamide of 1,2-ben-
zothiazine 1,1-dioxide, was the first member of the family of
NSAIDs (Non-steroidal anti-inflammatory drugs) used as an
inhibitor of prostaglandin biosynthesis, but, as the other
NSAIDs, it showed gastrointestinal and renal toxicity. Also,
it is known that several 1,2-thiazines and their benzo deriva-
tives have been used as anti-pyretic and anti-inflammatory
agents [1]. Other 3,6-dihydrothiazines are precursors for the
stereoselective synthesis of vicinal amino alcohols, diamines
and highly functionalized amines [2, 3]. Sulfoximides, im-
portant from the biological view, can be also employed as
precursors for the synthesis of 1,2-thiazines 1-oxide [4].
Moreover, many patents have been issued claiming the use
of sulfoximides as defoliant, herbicide, antifungal agent,
antihypertensive, and CNS (Central nervous system) depres-
sant [5]. On the other hand, the introduction of a trifluoro-
methyl group into many bioactive molecules has sometimes
resulted in significant enhancement of their potency and du-
ration of their action due to the increase of lipophilicity [6].
In a previous study, a series of 4-dimethylsulfoximide-
1,1,1-trifluorobut-3-en-2-ones was prepared by the direct
reaction of 4-alkyl(aryl)-4-alkoxy-1,1,1-trifluorobut-3-en-2-
ones with S,S-dimethylsulfoximide, in 50 – 95 % yields. In
the same study, six 5-trifluoromethylated 3-alkyl or 3-aryl-1-
methyl-1,2-thiazines 1-oxide derivatives were synthesized in
40 – 76 % yields, by intramolecular cyclization reaction of
the respective dimethylsulfoximido enones when the reac-
tions were carried out in presence of sodium methoxide or
ethoxide in methanol or ethanol, respectively [13]. However
this method only allows the attainment of non fused-bicyclic
1,2-thiazines.
In 1993, several fused N-substituted thieno[1,2]thiazines
were reported to be very potent carbonic anhydrase inhibi-
tors, useful for treating conditions which derive from the
restriction of blood flow to the brain [14]. Thus, for biologi-
cal evaluations it seemed desirable to develop a general
method for the synthesis of new fused thieno[1,2] thiazines,
which allow for the introduction of trifluoromethyl, alkyl or
aryl substituents to this interesting aza heterocyclic family
with the isolation of enaminoketone intermediates (new
acyclic sulfoximides).
The synthesis of 1,2-thiazines has been relatively well
explored via [4+2] cycloadditions. In general, the most
common 1,2-thiazines either have an alkyl, aryl, acyl or a
sulfonyl moiety at the 2 position (N-substituents) and a very
stable hexavalent sulfur at the ring, as for example 1,1-
dioxides [7]. Examples of 1,2-thiazines 1-oxide have been
synthesized by intramolecular cyclization [8], however, the
reactions are usually carried out in dimethylsulfoxide or
N,N-dimethylformamide and sodium hydride under argon or
2. RESULTS AND DISCUSSION
In this study, an efficient method for the synthesis of a
series of new 4-alkyl(aryl)-4-tetramethylenesulfoximide-
1,1,1-trifluoroalk-3-en-2-ones (2a-k) from ꢀ-trifluoroacetyl-
ated enol ethers [15] or acetals [16, 17], and an interesting
synthetic application using intramolecular cyclization reac-
tions to give new cycloalkane geminated 1,2-thiazines 1-
oxide (3c-j), is reported (Scheme 1).
*Address correspondence to this author at the Núcleo de Química de Hete-
rociclos (NUQUIMHE), Departamento de Química, Universidade Federal
de Santa Maria - 97105-900 - Santa Maria, RS - Brazil; Tel/Fax: +55 (55)
3220 8031; E-mail: heligb@base.ufsm.br
1570-1786/09 $55.00+.00
© 2009 Bentham Science Publishers Ltd.

146 Letters in Organic Chemistry, 2009, Vol. 6, No. 2
Bonacorso et al.
CF3
ii
S
R1
N
R1
O
R1
O
O
3c-j
60-85%
i
F3C
N
S
F3C
OR
65-97%
1a-k
O
2a-k
F3C
OH
ii
72%
(i) =S,S- tetramethylenesulfoximide, 100 °C, 2 hours.
(ii) = t-BuOK, Et2O, reflux, 3 hours.
S
R1
N
O
4k
1-4
R
a
b
c
d
e
f
g
h
i
j
k
Et Me Me
Me
Me
Me
Me
Me
Me
Me
Me
R1
H
Me Ph 4-MePh 4-OMePh 4-FPh 4-ClPh 4-BrPh 4-NO2Ph 4-4’-Biphenyl 1-Naphthyl
Scheme 1. Synthetic Route for thieno-thiazine system.
As a general procedure, firstly the trifluoromethyl enones
(1a-k) were treated with S,S-tetramethylenesulfoximide in
absence of solvent at 100 °C giving the new 4-alkyl(aryl)-4-
tetramethylene-sulfoximide-1,1,1-trifluoroalk-3-en-2-ones
(2a-k) in 65% to 95% yield. These new compounds (2a-k)
have been employed to obtain 3-aryl-5-trifluoromethyl-7,8-
dihydro-6H-thieno[2,1-f][1,2]thiazines 1-oxide (3c-j) by
intramolecular cyclization reaction, in good yields. The in-
novation in this synthetic route was the use of commercially
available potassium t-butoxide to substitute sodium methox-
ide or ethoxide in methanol or ethanol under reflux, respec-
tively, or to substitute sodium hydride in dimethylsulfoxide
or N,N-dimethylformamide under argon or nitrogen [7-12].
The reactions described here were easily carried out in the
presence of potassium t-butoxide in refluxing diethyl ether
without an argon or nitrogen atmosphere (Scheme 1). Sur-
prisingly, using this simple reaction condition, tetrahydrothi-
azine 4k was isolated as a pure compound from 2k.
protons (H-3) as a singlet in the range of 5.88-6.75 ppm. The
1H NMR spectrum for 2a showed a doublet at 8.27 ppm for
the olefenic proton H-4 and another doublet at 5.96 ppm for
1
the other olefinic proton H-3. The analysis of the H NMR
spectrum for 2a gives a coupling constant of 12 Hz for the
olefinic protons, which suggests an E configuration at the
olefinic bond [13, 18]. However, in the case of compounds
2i and 2k, which have substituents R1 = NO2 and 1-naphthyl,
respectively, there was a mixture of isomers E and Z at the
1
olefinic bond, with double signals in the H NMR and 13C
NMR spectra. In addition, compounds 2a-k showed the sig-
nals for the tetramethylene hydrogens H-5 and H-8 together
as a multiplet in the range of 3.31 - 3.64 ppm, and tetrame-
thylene protons H-6 and H-7 also together as a multiplet in
the range of 2.16 - 2.35 ppm. The 13C NMR spectra for com-
pounds 2a-k showed the carbonyl carbon (C-2) at an average
of 176.5 ppm as a quartet with JCF = 32 - 33 Hz, C-4 quater-
nary in the range of 155.8 - 189.2 ppm, CF3 group in the
range of 117.0 - 118.5 ppm as a quartet with JCF = 292 Hz,
C-3 chemical shifts at an average of 97.7 ppm and
tetramethylene carbons at an average of 56 ppm (C-5 and C-
8), 23.5 ppm (C-5 and C-8).
One can see that the problematic step in this synthetic
route, as outlined in the Scheme 1, was the intramolecular
cyclization of 2 to give respective thiazines 3 when the com-
pounds 2 are non-substituted or alkyl-substituted at carbon-4
(2a-b).
1
The 1,2-thiazines 1-oxide (3c-j) showed H NMR chemi-
cal shifts of the aromatic proton (H-4) as a singlet at an aver-
age of 6.52 - 6.71 ppm, tetramethylene protons as a multiplet
at an average of 3.75 ppm (H-8a), 3.47 ppm (H-8b), 3.35
ppm (H-6a), 3.20 ppm (H-6b), 2.57 ppm (H-7a) and 2.31
ppm (H-7b). The 13C NMR spectra of compounds 3c-j
showed chemical shifts of C-3 at an average of 152 ppm, C-5
at an average of 133 ppm as a quartet with JCF =33 Hz, CF3
in the range of 121.4 - 122.8 ppm as a quartet with JCF = 276
Hz, C-5a at an average of 105 ppm, C-4 at an average of 95
ppm, tetramethylene carbons at an average of 53.5 ppm (C-
8), 26.2 ppm (C-6) and 20.1 ppm (C-7).
Unfortunately, poor yields or unidentified dark products
were obtained by NMR experiments when the intramolecular
cyclization reaction of the respective dimethylsulfoximido
enones 2a and 2b were carried out in presence of sodium
methoxide or ethoxide in methanol or ethanol under reflux,
respectively. Attempts to accomplish the synthesis of 2a-b
failed even when potassium hydroxide or sodium hydride
was used as base.
1
The unambiguous H and 13C NMR chemical shift as-
signments of enones 2a-k and the thiazines 3c-j were ob-
tained with the help of 1D- and DEPT 135-NMR experi-
ments and by comparison with NMR data of other 1,2-
thiazines 1-oxide formerly synthesized in our laboratory
[13].
3. CONCLUSION
In summary, the methodology described in this work al-
lows attainment in a single structure of the strong electron
withdrawing effect of the CF3 group, the high bioactive-
The aryl-tetramethylenesulfoximide enones (2b-k),
1
showed H NMR chemical shifts, in CDCl3, of the olefinic

An Easy Approach to the Synthesis of New Fused
Letters in Organic Chemistry, 2009, Vol. 6, No. 2
147
versatility of the sulfoximide group and a large scope for aryl
substituents in cyclic and acyclic new interesting molecules.
7.42 (m, 2H, Ar), 6.21 (s, 1H, H-3), 3.59 (m, 4H, H-5, H-8),
2.32 (m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 176.4 (q, 2J =
32, C-2), 164.5 (C-4), 139.8, 130.9; 128.3; 128.2; (6C, Ar),
1
117.1 (q, J = 292, CF3), 97.7 (C-3), 56.6 (C-5, C-8), 23.4
4. EXPERIMENTAL
(C-6, C-7). GC/MS (EI, 70 eV): m/z (%) for C14H14NO2SF3
(317.07): 317 (M+, 20), 55 (100), 248 (90), 116 (87), 77(60),
146 (40). IR (KBr, ꢁ cm-1): 1675 (C=O), 1060 (S=O). Anal.
Calcd. for C14H14NO2SF3 (317.07): C, 52.99; H, 4.45; N,
4.41%. Found: C, 52.59; H, 4.33; N, 4.45%.
Unless otherwise indicated, all common reagents and
solvents were used as obtained from commercial suppliers
without further purification. All melting points were deter-
mined on a Reichert Thermovar apparatus and were uncor-
1
rected. H and 13C NMR spectra were acquired on a Bruker
DPX 400 spectrometer (1H at 400.13 MHz and 13C at 100.62
MHz), 5 mm sample tubes, 298 K, digital resolution ±0.01
ppm, in CDCl3 or DMSO-d6 (4k) using TMS as internal ref-
erence. Mass spectra were recorded in a HP 5973 MSD con-
nected to a HP 6890 GC and interfaced by a Pentium PC.
The GC was equipped with a split-splitless, injector, auto
sampler, cross-linked HP-5 capillary column (30m 0.32 mm
of internal diameter), and helium was used as the carrier gas.
Infrared spectra were recorded as KBr discs using a Bruker
Tensor 27 spectrometer over the range 4000-400 cm-1. The
CHN elemental analyses were performed on a Perkin Elmer
2400 CHN elemental analyzer (São Paulo University-
USP/Brazil).
4-(4-Tolyl)-4-tetramethylenesulfoximide-1,1,1-trifluorobut-
3-en-2-one (2d)
This compound was obtained as yellow solid; yield 74%;
1
Mp. 121-123 °C. H NMR (CDCl3) ꢀ = 7.58 (m, 2H, Ar),
7.22 (m, 2H, Ar), 6.18 (s, 1H, H-3), 3.55 (m, 4H, H-5, H-8),
2.39 (s, 3H, CH3), 2.33 (m, 4H, H-6, H-7). 13C NMR (CD-
2
Cl3) ꢀ = 176.1 (q, J =32.5, C-2), 164.6 (C-4), 141.5; 136.7;
1
128.9; 128.3 (6C, Ar), 117.2 (q, J =292, CF3), 97.0 (C-3),
56.3 (C-5, C-8), 23.3 (C-6, C-7), 21.3 (CH3). GC/MS (EI, 70
eV): m/z (%) for C15H16NO2SF3 (331.09): 331 (M+, 25), 55
(100), 262 (100), 130 (95), 146 (56), 158 (43). IR (KBr, ꢁ
cm-1): 1682 (C=O), 1063 (S=O). Anal. Calcd. for
C15H16NO2SF3 (331.09): C, 54.37; H, 4.87; N, 4.23%.
Found: C, 53.97; H, 4.68; N, 4.37%.
General Procedure for the Preparation of 4-Alkyl(aryl)-
4-tetramethylenesulfoximide-1,1,1-trifluorobut-3-en-2-
ones (2a-k)
4-(4-Methoxyphenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2e)
This compound was obtained as yellow solid; yield 71%;
Mp. 114-116 °C. H NMR (CDCl3) ꢀ = 7.82 (m, 2H, Ar),
A stirred mixture of 4-alkoxy-1,1,1-trifluoro-3-buten-2-
ones (1a-k) (10 mmol) and S,S-tetramethylenesulfoximide
(10 mmol) was heated in an oil bath in absence of solvent for
2 h at 100 °C for 2b-k or 30 min for 2a. After cooling, the
solid residues 2a-k were recrystallized from ethanol.
1
6.91 (m, 2H, Ar), 6.17 (s, 1H, H-3), 3.87 (s, 3H, OCH3), 3.58
(m, 4H, H-5, H-8), 2.32 (m, 4H, H-6, H-7). 13C NMR (CD-
Cl3) ꢀ = 175.3 (q, 2J =32, C-2), 164.3 (C-4), 161.9 (1C, Ar),
117.5 (q,1J =292, CF3), 130.2, 113.2 (5C, Ar), 95.4 (C-3),
55.5 (C-5, C-8), 54.9 (OCH3), 23.0 (C-6, C-7). GC/MS (EI,
70 eV): m/z (%) for C15H16NO3SF3 (347.08): 347 (M+, 24),
146 (100), 278 (55), 174 (33), 55 (35). IR (KBr, ꢁ cm-1):
1664 (C=O), 1059 (S=O). Anal. Calcd. for C15H16NO3SF3
(347.08): C, 51.87; H, 4.64; N, 4.03%. Found: C, 51.39; H,
4.18; N, 3.93%.
(E)-4-Tetramethylenesulfoximide-1,1,1-trifluorobut-3-en-
2-one (2a)
This compound was obtained as white solid; yield 65%;
1
Mp.106-108 °C. H NMR (CDCl3) ꢀ = 8.27 (d, 1H, J =12,
H-4), 5.96 (d, 1H, J =12, H-3), 3.37 (m, 4H, H-5, H-8), 2.37
2
(m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 179.4 (q, J = 33,
C-2), 155.8 (C-4), 117.1 (q, 1J = 292, CF3), 103.3 (C-3), 54.1
(C-5, C-8), 23.5 (C-6, C-7). GC/MS (EI, 70 eV): m/z (%) for
C8H10NO2SF3 (241.04): 241 (M+, 16), 172 (100), 105 (39),
55 (60). IR (KBr, ꢁ cm-1): 1666 (C=O), 1077 (S=O). Anal.
Calcd. for C8H10NO2SF3 (241.04): C, 39.83; H, 4.18; N,
5.81%. Found: C, 39.71; H, 3.83; N, 5.69%.
4-(4-Fluorophenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2f)
This compound was obtained as yellow solid; yield 70%;
1
Mp.112-113 °C. H NMR (CDCl3) ꢀ = 7.71 (m, 2H, Ar),
7.08 (m, 2H, Ar), 6.17 (s, 1H, H-3), 3.58 (m, 4H, H-5, H-8),
2
2.29 (m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 176.3 (q, J
4-Tetramethylenesulfoximide-1,1,1-trifluoropent-3-en-2-
one (2b)
=33, C-2), 166.9 (C-4), 161.9, 135.4, 130.7, 115.0, (6C, Ar),
117.2 (q, 1J =292, CF3), 97.2 (C-3), 56.2 (C-5, C-8), 23.4 (C-
6, C-7). GC/MS (EI, 70 eV): m/z (%) for C14H13NO2SF4
(335.06): 355 (M+, 32), 55 (100), 266 (92), 134 (80), 146
(65), 162 (29). IR (KBr, ꢁ cm-1): 1666 (C=O), 1065 (S=O).
Anal. Calcd. for C14H13NO2SF4 (335.06): C, 50.15; H, 3.91;
N, 4.18%. Found: C, 50.07; H, 3.56; N, 4.21%.
This compound was obtained as white solid; yield 71%;
1
Mp.109-111 °C. H NMR (CDCl3) ꢀ = 5.88 (s, 1H, H-3),
3.54 (m, 2H, H-5), 3.35 (m, 2H , H-8), 2.45 (s, 3H, CH3),
2.33 (m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 177.1 (q, 2J =
1
32, C-2), 173.3 (C-4), 117.2 (q, J = 292, CF3), 98.4 (C-3),
53.3 (C-5, C-8), 24.6 (CH3), 23.7 (C-6, C-7). GC/MS (EI, 70
eV): m/z (%) for C9H12NO2SF3 (255.05): 255 (M+, 6), 55
(100), 186 (55), 82 (15). IR (KBr, ꢁ cm-1): 1660 (C=O), 1096
(S=O). Anal. Calcd. for C9H12NO2SF3 (255.05): C, 42.35; H,
4.74; N, 5.49%.Found: C, 42.23; H, 4.77; N, 5.44%.
4-(4-Chlorophenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2g)
This compound was obtained as yellow solid; yield 90%;
1
Mp. 148-150 °C. H NMR (CDCl3) ꢀ = 7.66 (m, 2H, Ar),
7.35 (m, 2H, Ar), 6.16 (s, 1H, H-3), 3.59 (m, 4H, H-5, H-8),
4-Phenyl-4-tetramethylenesulfoximide-1,1,1-trifluorobut-3-
en-2-one (2c)
2
2.29 (m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 176.5 (q, J
=32, C-2), 162.7 (C-4), 138.3, 137.1, 129.6, 129.3, 128.8,
This compound was obtained as yellow solid; yield 97%;
128.3 (6C, Ar), 117.1 (q, 1J =292, CF3), 97.3 (C-3), 56.7 (C-
1
Mp. 136-138 °C. H NMR (CDCl3) ꢀ = 7.73 (m, 2H, Ar),

148 Letters in Organic Chemistry, 2009, Vol. 6, No. 2
Bonacorso et al.
5), 54.5 (C-8), 23.4 (C-6, C-7). GC/MS (EI, 70 eV): m/z (%)
for C14H13ClNO2SF3 (351.03): 351 (M+, 18), 55 (100), 282
(77), 150 (53) 146 (55), 178 (16). IR (KBr, ꢀ cm-1): 1670
(C=O), 1063 (S=O). Anal. Calcd. for C14H13ClNO2SF3
(351.03): C, 47.80; H, 3.42; N, 3.98%. Found: C, 47.69; H,
3.44; N, 3.98%.
7). GC/MS (EI, 70 eV): m/z (%) for C18H16NO2SF3 (367.09):
367 (M+, 20), 166 (100), 298 (38), 270 (20), 194 (25), 146
(35), 127 (50), 55 (45). IR (KBr, ꢀ cm-1): 1676 (C=O), 1059
(S=O). Anal. Calcd. for C18H16NO2SF3 (367.09): C, 58.85;
H, 4.39; N, 3.81%. Found: C, 58.78; H, 4.20; N, 3.62%.
4-(4-Bromophenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2h)
General Procedure for the Preparation of 3-Aryl-5-
trifluoromethyl-7,8-dihydro-6H-thieno [2,1-f] [1,2] thia-
zines 1-oxide (3c-j) and 3-(1-Naphthyl)-5-trifluormethyl-
5-hidroxy-5a,6,7,8-tetrahydro-5H-thieno [2,1-f] [1,2] thi-
azine 1-oxide (4k)
This compound was obtained as yellow solid; yield 73%;
1
Mp. 159-161 °C. H NMR (CDCl3) ꢁ = 7.54 (m, 4H, Ar),
6.17 (s, 1H, H-3), 3.59 (m, 4H, H-5, H-8), 2.30 (m, 4H, H-6,
2
H-7). 13C NMR (CDCl3) ꢀ = 176.6 (q, J =32, C-2), 162.7
Compounds 4-aryl-4-tetramethylenesulfoximide-1,1,1-
trifluoro- but-3-en-2-ones (2c-j) (2 mmol) were dissolved in
15 ml of dry diethyl ether. Potassium t-butoxide (2.2 mmol)
was added in one portion. The resulting slurry solutions were
stirred under reflux for 3 h. The products were acidified by
the addition of 1 ml of acetic acid followed by 10 ml of wa-
ter. The organic phase was washed with brine, dried over
Na2SO4, and concentrated under reduced pressure. The solid
residues (3c-j) and (4k) were recrystallized from ethanol.
1
(C-4), 138.9, 131.4, 129.8 (6C, Ar), 117.1 (q, J =292, CF3),
97.6 (C-3), 56.7 (C-5, C-8), 23.5 (C-6, C-7). GC/MS (EI, 70
eV): m/z (%) for C14H13BrNO2SF3 (396.98): 397 (M+, 10), 55
(100), 328 (53), 196 (30), 146 (52), 224 (10). Anal. Calcd.
for C14H13BrNO2SF3 (396.98): C, 42.44; H, 3.31; N, 3.54%.
Found: C, 41.94; H, 3.12; N, 3.69%.
4-(4-Nitrophenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2i)
3-Phenyl-5-trifluoromethyl-7,8-dihydro-6H-thieno [2,1-f]
[1,2] thiazine 1-oxide (3c)
This compound was obtained as brown solid; yield 80%;
Mp.130-132 °C. Data is from the mixture of isomers E and Z
(1: 0.7, from NMR). 1H NMR (CDCl3) ꢁ = 8.22 (m, 4H, Ar),
7.88 (m, 2H, Ar), 7.53 (m, 2H, Ar), 6.22, 6.13 (s, 2H, H-3),
3.64 (m, 8H, H-5, H-8), 2.35 (m, 8H, H-6, H-7). 13C NMR
This compound was obtained as brown solid; yield 85%;
1
Mp.107-109 °C. H NMR (CDCl3) ꢁ = 7.91 (m, 2H, Ar),
7.43 (m, 3H, Ar), 6.65 (s, 1H, H-4), 3.78 (m, 1H, H-8a), 3.49
(m, 1H, H-8b), 3.35 (m, 1H, H-6a), 3.20 (m, 1H, H-6b), 2.57
(m, 1H, H-7a), 2.32 (m, 1H, H-7b). 13C NMR (CDCl3) ꢀ =
2
(CDCl3) ꢀ = 176.6 (q, J =33, C-2), 167.9, 160.8 (C-4),
149.0, 148.2, 145.3, 144.8, 129.3, 129.0, 123.4, 123.1 (12C,
Ar), 117.1 (q, 1J =292, CF3), 98.7, 98.1 (C-3), 56.9, 53.3 (C-
5, C-8), 23.8, 23.4 (C-6, C-7). GC/MS (EI, 70 eV): m/z (%)
for C14H13N2O4SF3 (362.05): 362 (M+, 10), 55 (100),
293(84), 189 (5), 161 (18), 146 (24). IR (KBr, ꢀ cm-1): 1658
(C=O), 1060 (S=O). Anal. Calcd. for C14H13N2O4SF3
(362.05): C, 46.41; H, 3.62; N, 7.73%. Found: C, 46.55; H,
3.37; N, 7.59%.
2
152.9 (C-3), 137.4 (1C, Ar), 133.0 (q, J=33, C-5), 129.8,
128.5, 127.3 (5C, Ar), 122.8 (q, 1J =276, CF3), 105.9 (C-5a),
95.7 (C-4), 53.6 (C-8), 26.2 (C-6), 20.2 (C-7). GC/MS (EI,
70 eV): m/z (%) for C14H12NOSF3 (299.06): 299 (M+, 73),
237 (100), 224 (72), 251 (60), 154 (55), 77 (40), 51 (46). IR
(KBr, ꢀ cm-1): 1049 (S=O). Anal. Calcd. for C14H12NOSF3
(299.06): C, 56.18; H, 4.04; N, 4.68%. Found: C, 56.09; H,
3.91; N, 4.63%.
4-(4,4’-Biphenyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2j)
3-(4-Tolyl)-5-trifluoromethyl-7,8-dihydro-6H-thieno [2,1-f]
[1,2] thiazine 1-oxide (3d)
This compound was obtained as yellow solid; yield 81%;
Mp.98-100 °C. 1H NMR (CDCl3) ꢁ = 8.00 (m, 2H, Ar), 7.64
(m, 4H, Ar), 7.42 (m, 3H, Ar), 6.75 (s, 1H, H-3), 3.52 (m,
4H, H-5, H-8), 2.24 (m, 4H, H-6, H-7). 13C NMR (CDCl3) ꢀ
This compound was obtained as brown solid; yield 73%;
1
Mp.117-119 °C. H NMR (CDCl3) ꢁ = 7.80 (m, 2H, Ar),
7.22 (m, 2H, Ar), 6.62 (s, 1H, H-4), 3.75 (m, 1H, H-8a), 3.47
(m, 1H, H-8b), 3.35 (m, 1H, H-6a), 3.18 (m, 1H, H-6b), 2.56
(m, 1H, H-7a), 2.30 (m, 1H, H-7b). 13C NMR (CDCl3) ꢀ =
2
= 189.2 (C-4), 177.2 (q, J =32, C-2), 145.2, 139.8, 136.9,
1
128.8, 128.7, 128.0, 127.1, 127.0 (12C, Ar), 121.2 (q, J
2
=278, CF3), 104.3 (C-3), 55.8 (C-5, C-8), 23.1 (C-6, C-7).
GC/MS (EI, 70 eV): m/z (%) for C20H18NO2SF3 (393.1): 393
(M+, 28), 181 (100), 324 (1), 289 (28), 152 (67), 55 (62).
Anal. Calcd. for C20H18NO2SF3 (393.10): C, 61.06; H, 4.61;
N, 3.56%. Found: C, 61.43; H, 4.48; N, 3.54%.
152.9 (C-3), 140.1, 134.6 (2C, Ar), 132.9 (q, J =33, C-5),
129.2, 127.1 (4C, Ar), 121.5 (q, 1J =276, CF3), 105.4 (C-5a),
95.2 (C-4), 53.6 (C-8), 26.2 (C-6), 21.2 (CH3), 20.1 (C-7).
GC/MS (EI, 70 eV): m/z (%) for C15H14NOSF3 (313.07): 313
(M+, 57), 251 (100), 238 (48), 264 (44), 168 (28), 91 (18). IR
(KBr, ꢀ cm-1): 1098 (S=O). Anal. Calcd. for C15H14NOSF3
(313.07): C, 57.50; H, 4.50; N, 4.47%. Found: C, 57.40; H,
4.32; N, 4.46%.
4-(1-Naphthyl)-4-tetramethylenesulfoximide-1,1,1-
trifluorobut-3-en-2-one (2k)
This compound was obtained as white solid; yield 84%;
Mp.134-136 °C. Data is from the mixture of isomers E and Z
3-(4-Methoxyphenyl)-5-trifluoromethyl-7,8-dihydro-6H-
thieno [2,1-f] [1,2] thiazine 1-oxide (3e)
1
(1: 0.5). H NMR (CDCl3) ꢁ = 7.85 (m, 6H, Ar), 7.44 (m,
8H, Ar), 6.37, 5.93 (s, 2H, H-3), 3.31-3.05 (m, 8H, H-5, H-
8), 2.16 (m, 8H, H-6, H-7). 13C NMR (CDCl3) ꢀ = 176.1 (q,
2J =32, C-2), 168.9, 165.5 (C-4), 137.4, 136.6, 133.2, 130.3,
129.9, 129.7, 128.8, 128.3, 126.7, 126.5, 126.2, 125.9, 125.2,
124.7, 124.5, 124.0 (20C, Ar), 113.9 (q, J =293, CF3),
102.9, 101.2 (C-3), 55.3, 53.3 (C-5, C-8), 23.2, 23.0 (C-6, C-
This compound was obtained as brown solid; yield 70%;
Mp.122-124 °C. H NMR (CDCl3) ꢁ = 7.85 (m, 2H, Ar),
6.93 (m, 2H, Ar), 6.57 (s, 1H, H-4), 3.85 (s, 3H, OCH3), 3.75
(m, 1H, H-8a), 3.46 (m, 1H, H-8b), 3.31 (m, 1H, H-6a), 3.18
(m, 1H, H-6b), 2.57 (m, 1H, H-7a), 2.31 (m, 1H, H-7b). 13C
NMR (CDCl3) ꢀ = 161.0 (1C, Ar), 152.6 (C-3), 132.9 (q,
1
1

An Easy Approach to the Synthesis of New Fused
Letters in Organic Chemistry, 2009, Vol. 6, No. 2
149
1
2
2J=33, C-5), 129.9, 128.7 (3C, Ar), 122.8 (q, J =275, CF3),
113.8 (2C, Ar), 104.8 (C-5a), 94.6 (C-4), 55.2 (OCH3), 53.5
(C-8), 26.1 (C-6), 20.1 (C-7). GC/MS (EI, 70 eV): m/z (%)
for C15H14NO2SF3 (329.07): 329 (M+, 85), 267 (100),
253(66), 280 (35), 184 (18). IR (KBr, ꢀ cm-1): 1035 (S=O).
Anal. Calcd. for C15H14NO2SF3 (329.07): C, 54.70; H, 4.28;
N, 4.25%. Found: C, 54.90; H, 4.08; N, 4.29%.
=149.7 (C-3), 148.2, 143.3 (2C, Ar), 132.6 (q, J =33, C-5),
127.7, 123.6 (4C, Ar), 122.5 (q, 1J =276, CF3), 108.9 (C-5a),
97.3 (C-4), 53.4 (C-8), 26.2 (C-6), 20.2 (C-7). GC/MS (EI,
70 eV): m/z (%) for C14H11N2O3SF3 (344.04): 344 (M+, 49),
295 (100), 222 (77), 283 (53), 269 (32), 249 (27), 153 (22).
IR (KBr,
ꢀ
cm-1): 1068 (S=O). Anal. Calcd. for
C14H11N2O3SF3 (344.04): C, 48.84; H, 3.22; N, 8.14%.
Found: 48.60; H, 3.16; N, 7.92%.
3-(4-Fluorophenyl)-5-trifluoromethyl-7,8-dihydro-6H-
thieno [2,1-f] [1,2] thiazine 1-oxide (3f)
3-(4,4’-Biphenyl)-5-trifluoromethyl-7,8-dihydro-6H-thieno
[2,1-f] [1,2] thiazine 1-oxide (3j)
This compound was obtained as brown solid; yield 82%;
Mp.122-124 °C. H NMR (CDCl3) ꢁ = 7.89 (m, 2H, Ar),
1
This compound was obtained as brown solid; yield 77%;
Mp.168-170 °C. H NMR (CDCl3) ꢁ = 7.71-7.42 (m, 9H,
Ar), 6.57 (s, 1H, H-4), 3.68 (m, 2H, H-8a e H-8b), 3.39 (m,
1H, H-6a), 3.05 (m, 1H, H-6b), 2.48 (m, 1H, H-7a), 2.07 (m,
1H, H-7b). 13C NMR (CDCl3) ꢀ = 142.8 (C-3), 142.5 (1C,
Ar), 139.9 (q, 2J=34, C-5), 139.8, 135.6, 129.3, 128.9, 127.9,
1
7.01 (m, 2H, Ar), 6.58 (s, 1H, H-4), 3.77 (m, 1H, H-8a), 3.47
(m, 1H, H-8b), 3.31 (m, 1H, H-6a), 3.19 (m, 1H, H-6b), 2.57
(m, 1H, H-7a), 2.32 (m, 1H H-7b). 13C NMR (CDCl3) ꢀ =
2
161.4 (1C, Ar), 151.8 (C-3), 133.6 (1C, Ar), 132.6 (q, J
1
=33, C-5), 129.3, 115.6 (4C, Ar), 122.8 (q, J=276, CF3),
1
106.1 (C-5a), 95.4 (C-4), 53.6 (C-8), 26.2 (C-6), 20.2 (C-7).
GC/MS (EI, 70 eV): m/z (%) for C14H11FNOSF3 (317.05):
317 (M+, 58), 255 (100), 243 (67), 172 (62), 270 (49), 95
(33). IR (KBr, ꢀ cm-1): 1098 (S=O). Anal. Calcd. for
C14H11NOSF4 (317.05): C, 52.99; H, 3.49; N, 4.41%. Found:
C, 51.55; H, 3.47; N, 4.26%.
127.4, 127.0 (11C, Ar), 121.4 (q, J =274, CF3), 111.1 (C-
5a), 101.8 (C-4), 54.4 (C-8), 27.7 (C-6), 21.1 (C-7). GC/MS
(EI, 70 eV): m/z (%) for C20H16NOSF3 (375.09): 375 (M+,
98), 326 (100), 230 (96), 309 (94), 283 (52), 202 (51), 313
(46), 257 (34), 152 (32). Anal. Calcd. for C20H16NOSF3
(375.09): C, 63.99; H, 4.30; N, 3.73%. Found: C, 63.73; H,
4.15; N, 4.02%.
3-(4-Chlorophenyl)-5-trifluoromethyl-7,8-dihydro-6H-
thieno [2,1-f] [1,2] thiazine 1-oxide (3g)
3-(1-Naphthyl)-5-trifluoromethyl-5-hidroxy-5a,6,7,8-
tetrahydro-5H-thieno [2,1-f] [1,2] thiazine 1-oxide (4k)
This compound was obtained as brown solid; yield 81%;
Mp.113-115 °C. H NMR (CDCl3) ꢁ = 7.76 (m, 2H, Ar),
7.30 (m, 2H, Ar), 6.52 (s, 1H, H-4), 3.68 (m, 1H, H-8a), 3.37
(m, 1H, H-8b), 3.25 (m, 1H, H-6a), 3.07 (m, 1H, H-6b), 2.47
(m, 1H, H-7a), 2.21 (m, 1H, H-7b). 13C NMR (CDCl3) ꢀ =
151.5 (C-3), 132.8 (q, 2J =33, C-5), 135.8, 128.6, 128.4, (6C,
1
This compound was obtained as brown solid; yield 72%;
Mp.168-170 °C. H NMR (DMSO-d6) ꢁ = 8.32 (m, 1H, Ar),
1
7.92 (m, 2H, Ar), 7.52 (m, 4H, Ar), 6.67 (s, 1H, H-4), 5.05
(s, 1H, OH), 3.88 (m, 1H, H-5a), 3.51 (m, 1H, H-8a), 3.44
(m, 1H, H-8b), 2.27 (m, 2H, H-6a e H-6b), 2.14 (m, 1H, H-
7a), 1.78 (m, 1H, H-7b). 13C NMR (DMSO-d6) ꢀ = 147.5 (C-
3), 138.1, 133.1, 130.3, 128.3, 128.0, 125.8, 125.7, 125.6,
125.1 (10C, Ar), 124.9 (q, 1J=286, CF3), 94.3 (C-4), 72.2 (q,
2J=29, C-5), 57.1 (C-5a), 51.7 (C-8), 24.7 (C-6), 18.4 (C-7).
1
Ar), 122.7 (q, J =276, CF3), 106.6 (C-5a), 95.6 (C-4), 53.5
(C-8), 26.2 (C-6), 20.1 (C-7). GC/MS (EI, 70 eV): m/z (%)
for C14H11ClNOSF3 (333.02): 333 (M+, 58), 271 (100), 259
(58), 287 (57), 111 (12). IR (KBr, ꢀ cm-1): 1085 (S=O). A-
nal. Calcd. for C14H11ClNOSF3 (333.02): C, 50.38; H, 3.32;
N, 4.20%. Found: C, 50.36; H, 3.24; N, 4.15%.
IR (KBr,
ꢀ
cm-1): 1061 (S=O). Anal. Calcd. for
C18H14NOSF3 (367.1): C, 58.85; H, 4.39; N, 3.81%. Found:
C, 58.61; H, 4.10; N, 4.18%
3-(4-Bromophenyl)-5-trifluoromethyl-7,8-dihydro-6H-
thieno [2,1-f] [1,2] thiazine 1-oxide (3h)
ACKNOWLEDGEMENT
This compound was obtained as brown solid; yield 80%;
Mp.123-125 °C. H NMR (CDCl3) ꢁ = 7.78 (m, 2H, Ar),
1
The authors are thankful for financial support from the
Conselho Nacional de Desenvolvimento Científico e Tecno-
lógico-CNPq (Process N° 473.864/2006-1) for financial sup-
port. Fellowship from Coordenação de Aperfeiçoamento de
Pessoal de Nível Superior-CAPES (for R.P.V.) is also ack-
nowledged.
7.55 (m, 2H, Ar), 6.61 (s, 1H, H-4), 3.81 (m, 1H, H-8a), 3.48
(m, 1H, H-8b), 3.36 (m, 1H, H-6a), 3.18 (m, 1H, H-6b), 2.59
(m, 1H, H-7a), 2.35 (m, 1H, H-7b). 13C NMR (CDCl3) ꢀ =
2
151.6 (C-3), 136.3 (1C, Ar), 132.9 (q, J=33, C-5), 131.6,
128.7, 124.3 (5C, Ar), 122.7 (q, 1J =276, CF3), 106.6 (C-5a),
95.7 (C-4), 53.6 (C-8), 26.2 (C-6), 20.2 (C-7). GC/MS (EI,
70 eV): m/z (%) for C14H11BrNOSF3 (378.21): 378 (M+, 49),
315 (100), 75 (78), 51 (68), 303 (61), 330 (60). IR (KBr, ꢀ
cm-1): 1073 (S=O). Anal. Calcd. for C14H11BrNOSF3
(378,21): C, 44.46; H, 2.93; N, 3.70%. Found: C, 44.75; H,
2.81; N, 3.71%.
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