Synthesis of 2,4-difuryl-4H-3,1-benzothiazines via a furan ring migration reaction

Article abstract of DOI:10.1002/jhet.5570450227

(Chemical Equation Presented) A new simple synthetic approach to 2,4-difuryl-4H-3,1-benzothiazines from 2-isothiocyanoaryldifurylmethanes in the presence of acidic catalyst is described. This rearrangement is a new example of furan ring migration reaction

Full text of DOI:10.1002/jhet.5570450227

Mar-Apr 2008
475
Synthesis of 2,4-Difuryl-4H-3,1-benzothiazines via a Furan Ring
Migration Reaction
Vladimir T. Abaev [a], Fatima A. Tsiunchik [b], Andrey V. Gutnov [c]
and Alexander V. Butin* [b]
[a] North-Ossetian State University, Vatutina St. 46, Vladikavkaz, 362025, Russian Federation
[b] Kuban State University of Technology, Moskovskaya St. 2, Krasnodar, 350072, Russian Federation
alexander_butin@mail.ru
[c] ChiroBlock GmbH, Andresenstr. 1a, D-06766 Wolfen, Germany
Received June 25, 2007
R"
R"
R"
O
O
O
R
R
O
+
R
S
R"
S
R'
N
R'
O
N
R'
N
R"
O
H
C
H+
R"
S
A new simple synthetic approach to 2,4-difuryl-4H-3,1-benzothiazines from 2-isothiocyanoaryldifuryl-
methanes in the presence of acidic catalyst is described. This rearrangement is a new example of furan ring
migration reaction resulting from intramolecular attack with electrophilic carbon.
J. Heterocyclic Chem., 45, 475 (2008).
alkaloids by intramolecular alkylation of furans with
acyliminium ions [6].
INTRODUCTION
Among the five-membered aromatic heterocycles furan
holds leading positions due to unique diversity of its
chemical transformations. For example furan compounds
can undergo substitution reactions as aromatic
compounds, cycloaddition reactions as dienes, can serve
as convenient precursors of 1,4-diketones and undergo
oxidation reactions. All these transformations are widely
used in synthetic practice [1]. It should be noted that
reactivity of furan compounds strongly depends on the
substrate structure and reaction conditions. Presently,
three types of intramolecular reactions of furans with
electrophilic carbon are known: cyclization, electrophilic
ring opening, and ring transfer (Scheme 1).
Scheme 1
TYPE 1
C+
H
+
O
R
R
R
O
O
TYPE 2
C+
+
R
R
O
R
The first type, the electrophilic cyclization is probably
the common intramolecular furan-carbocation reaction. It
includes intramolecular alkylation, acylation and conden-
sation reactions leading to a new ring formation. Furan
compounds with alkene side chain are prone to acid
catalyzed intramolecular alkylation, and the reaction is
commonly used in natural products synthesis. In
O
H
O
TYPE 3
C+
O
C+
+
R
R
R
O
O
particular,
a
synthesis of furanosesquiterpenoid
Pallescensin A and its derivatives was reported [2] as well
as formal total syntheses of Aphidicolin [3] and
substances structurally related to natural Guaianolides
and Pseudoguaianolides [4]. Katritzky et al offered a
general and facile synthesis of furocarbazoles based on
the intramolecular furan alkylation with benzotriazole as a
leaving group [5]. Tanis et al synthesized furyl containing
Intramolecular acylation, which takes place in the
presence of acidic catalysts and leads to a new benzene
ring formation, is widely used in the synthesis of
naphthofuran [7] and benzofuran [8] skeletons. Similar
intramolecular electrophilic cyclizations are also
successfully used to build up naphthofuran [7f, 7g] and
benzofuran [9] heterocyclic systems. Recently we applied

476
V. T. Abaev, F. A. Tsiunchik, A. V. Gutnov and A. V. Butin
Vol 45
In this case the reaction does not proceed through a
classical electrophilic cyclization as initially thought but
is accompanied with furan ring transfer and it is therefore
a new example of transformations of such type. In the
present publication we describe results of detailed
investigation of this rearrangement.
the reaction to obtain a number of seven-membered
furoannelated carbocycles [10].
The second type, the electrophilic cleavage of furan
ring leading to α,β-unsaturated ketones is less known, but
represented in several publications. It is described as a
result of intramolecular reaction of furan ring with
carbenes which are generated from furyl α-diazoketones
under catalysis with Cu(II) [11] and Rh(II) [12] or from
furyl acetylenes under catalysis with PtCl2 [13]. Most
interesting is the synthesis of benzo[a]azulenyl- [14] and
azuleno[1,2-b]thienyl- [15] α,β-unsaturated ketones by
Yamamura et al based on the reaction of cycloheptatrienyl
cation which is connected with furan via benzene and
thiophene rings respectively.
The third type of furan-carbocation reactions is
accompanied with furan ring transfer and as we known it
is represented by a single publication. It was reported that
treatment of aminoalcohols 1 with trifluoroacetic acid led
to the cyclization product 2 with low yield in only one
case. The major products of the reaction were identified
RESULTS AND DISCUSSION
Isothiocyanates 7 were the starting compounds for our
synthesis of 4H-3,1-benzothiazine derivatives (Scheme 3,
Table 1). 2-Nitroaryldihetarylmethanes 5 were prepared
by condensation of 2-nitrobenzaldehydes 4 with furans
and 2-methylthiophene in CH2Cl2 in the presence of
polyphosphoric acid trimethylsilyl ether (Si-PPA) at r.t.,
the method earlier reported by our group [20]. The
compounds 5 were reduced to corresponding amines 6
with hydrazine hydrate in the presence of Raney nickel. 2-
Isothiocyanoaryldihetarylmethanes 7 were synthesized by
treatment of amines 6 with thiophosgene in CH2Cl2/aq.
NaHCO3 biphasic system.
as isomeric tetrahydrofuro[3,2-c]pyridines
3
which
resulted from rearrangement and furan ring transfer to
Scheme 3
carbocation A (Scheme 2) [16].
R"
Scheme 2
CHO
NO2
X
R
X
Si-PPA
CH2Cl2
R"
+
R'
R'
R
R'
X
R'
R"
R"
R"
R"
4
R'
NO2
5a-i
TFA
+
HO
R"
R"
+
O
R
R
NMe
NMe
NMe
O
R
X
X
O
A
1
R
R
CSCl2
NaHCO3
X
X
Ni-Ra
R"
R"
NH2NH2
R'
NCS
R'
R'
NH2
6a-i
NMe
R
R"
7a-i
O
Treatment of 2-isothiocyanoaryldifurylmethanes 7a-h
with 70% HClO4 in 1,4-dioxane at r.t. leads to 2,4-difuryl-
4H-3,1-benzothiazine derivatives 8a-h in with 57-70%
yield (Scheme 4, Table 2). Alkyl substituents (methyl,
ethyl, t-butyl) in the position 5 of furan ring do not
influence the course of the reaction. The reaction follows
the same reaction pathway with comparable rates and is
completed within 5 hours in average. Fluctuations in
yields are caused most likely by isolation procedures for a
particular compound.
Replacement of alkyl group in the position 5 of furan
ring by aromatic group in the compound 7d also leads to
benzothiazine 8d after rearrangement, with the only
difference being an increase in the reaction time to 3 days
at r.t. Elevated temperatures resulted in noticeable
decomposition of the reaction mixture and lower yields of
the target compound.
R"
R
NMe
R'
O
3
2
Isothiocyanates are well known reagents for Friedel-
Crafts reaction with aromatic and heterocyclic compounds
to give thioamides in the presence of acidic catalysts [17],
and isothiocyano carbon atom is acting as electrophile in
the aromatic substitution. Similar intramolecular cycli-
zation reactions are also known for compounds with
isothiocyano group bound with aromatic and hetero-
aromatic rings via alkyl spacers [18].
In a preliminary communication [19], we reported two
examples of perchloric acid catalyzed transformation of 2-
isothiocyanoaryldifurylmethanes into corresponding 2,4-
difuryl-4H-3,1-benzothiazine derivatives in 1,4-dioxane.

Mar-Apr 2008
Synthesis of 2,4-Difuryl-4H-3,1-benzothiazines via a Furan Ring Migration Reaction
477
Table 1
Yields of Compounds 5, 6 and 7
Entry
R
R’
OCH2O
OCH2O
OCH2O
OCH2O
OCH2CH2O
OMe
R”
Me
X
O
O
O
O
O
O
O
O
S
Yield of 5 (%)
Yield of 6 (%)
Yield of 7 (%)
a
b
c
d
e
f
83
85
82
43
91
87
60
84
57
92
90
95
85
94
88
78
81
93
77
79
83
85
82
75
75
78
85
Et
t-Bu
p-BrC6H4
Me
OMe
H
Me
g
h
i
Br
Me
H
H
Me
H
H
Me
Scheme 4
did not change in this case, but the reaction time could be
also reduced to 4 hours for compound 7d and 30-60 min
for the rest of the substrates.
R"
X
R"
X
HClO4
R
R
X
S
R"
R'
N
R'
NCS
7a-i
X
8a-i
R"
Table 2
Yields of the Compounds 8
Entry
R
R’
R”
Me
X
O
O
O
O
O
O
O
O
S
Yield of 8 (%)
a
b
c
d
e
f
OCH2O
OCH2O
OCH2O
OCH2O
65
64
57
48
65
68
59
70
45
Et
Figure 1. ORTEP diagram of 8e.
t-Bu
p-BrC6H4
Me
A plausible mechanism for the rearrangement of 7 to 8
is proposed as shown in Scheme 5. We believe that
isothiocyano group activated with proton or AlCl3 is able
OCH2CH2O
OMe OMe
Br
Me
Me
g
h
i
H
H
H
H
H
Me
Me
Scheme 5
2,4-Difuryl-4H-3,1-benzothiazine derivatives 8a-h were
fully characterized by spectral methods. For unambiguous
proof of structure X-Ray analysis was performed for 8e
(Figure 1) [21].
R"
R"
X
X
R"
X
+
R
X
R
To extend the scope of the reaction, rearrangement to
2,4-dithienyl-4H-3,1-benzothiazine was investigated.
Treatment of (2-isothiocyanoaryl)dithienylmethane 7i
with 70% HClO4 in 1,4-dioxane at 80-85 °C for 8 hours
furnished the corresponding 2,4-dithienyl-4H-3,1-benzo-
thiazine 8i in with 45% yield (Scheme 4, Table 2). The
moderate yield of the product stimulated us to explore
other reaction conditions. It was found that the catalyst
of choice is anh. AlCl3 (1.5 eq.) in 1,2-dichloroethane at
r.t. The product 8i was obtained in 72% yield under
these conditions and the reaction time was reduced to
40 min. The same conditions were applied to the
rearrangement of aryldifurylmethanes 7a-h. The yields
R"
R'
R'
S
N
H
N
C
H+
B
S
7
R"
R"
X
X
R
+
R
S
S
X
R'
N
R'
N
R"
X
H
8
R"

478
V. T. Abaev, F. A. Tsiunchik, A. V. Gutnov and A. V. Butin
Vol 45
6-Bis[5-(tert-butyl)-2-furyl]methyl-1,3-benzodioxol-5-yl
isothiocyanate (7c). This compound was obtained according to
the general method in 83% yield as pale beige solid (hexane),
mp 126-127 °C; ir (potassium bromide): 2127, 1504, 1483,
1461, 1369, 1297, 1249, 1193, 1180, 1124, 1070, 1039, 1018,
to attack the α-position of heterocycle followed by C-C
bond cleavage and carbocation B formation. Therefore,
the first step of the reaction is the transfer of heterocycle
from one carbon to another. Subsequent nucleophilic
attack of the thioamide sulfur atom to the carbocationic
center furnishes the formation of the thiazine cycle.
In conclusion, a new synthetic approach to 2,4-difuryl-
4H-3,1-benzothiazine derivatives has been developed
based on a novel intramolecular furan ring migration
reaction as a key step. It was shown that the rearrange-
ment can be extended to the 2,4-dithienyl-4H-3,1-benzo-
thiazine derivatives.
1
979, 939, 871, 784 cm-1; H nmr (200 MHz, deuteriochloro-
form): δ 1.26 (s, 18H, t-Bu), 5.61 (s, 1H, CH), 5.88 (d, J = 3.2
Hz, 2H, 4-HFur), 5.92 (d, J = 3.2 Hz, 2H, 3-HFur), 5.98 (s, 2H,
CH2), 6.62 (s, 1H, HAr), 6,74 (s, 1H, HAr). Anal. Calcd. for
C25H27NO4S: C, 68.63; H 6.22; N, 3.20. Found: C, 68.78; H
6.17; N, 3.34.
6-Bis[5-(4-bromophenyl)-2-furyl]methyl-1,3-benzodioxol-
5-yl isothiocyanate (7d). This compound was obtained
according to the general method in 85% yield as pale green solid
(hexane), mp 142 °C; ir (potassium bromide) 2125, 2102, 1502,
1477, 1467, 1377, 1242, 1197, 1072, 1033, 1006, 827, 800, 781
EXPERIMENTAL
1
cm-1; H nmr (200 MHz, deuteriochloroform): δ 5.89 (s, 1H,
Melting points are uncorrected. 1H NMR and 13C NMR
spectra were recorded in CDCl3 and DMSO-d6 on a Bruker AC
200, Bruker AM 300 and Bruker AM 360 spectrometers.
Chemical shifts are reported in ppm relative to tetramethylsilane
as an internal standard and coupling constants (J) are given in
absolute values in Hz to the nearest 0.1 Hz. Mass spectra were
recorded on a Kratos MS-30 instrument with 70 eV electron
impact ionization at 200ºC. IR spectra were recorded on
InfraLUM FT-02 and InfraLUM FT-801. Column chroma-
tography was carried out using silica gel KSK (5-40 µm)
manufactured by LTD Sorbpolymer. A single crystal of 8e
suitable for X-Ray crystallography was grown from AcOEt-
hexane. Compounds 5 were synthesized according published
method [20], compounds 6 were synthesized as described [10e].
General procedure for the synthesis of isothiocyanates
7a-i. To a stirred solution of the compound (6) (5 mmol) in
CH2Cl2 (15 ml) solutions of CSCl2 (0.5 ml, 6.6 mmol) in CH2Cl2
(5 ml) and NaHCO3 (1.5 g, 18 mmol) in water (50 ml) were
added simultaneously at r.t. At the end of the reaction
(monitored by TLC) the mixture was poured into water (200 ml)
and stirred for 6 hours. The organic layer was extracted with
CH2Cl2 (2 × 40 ml), separated and dried over anhydrous Na2SO4.
The solvent was evaporated and the oily residue was dissolved
in hot hexane and filtered through a pad of silica gel (5-40 µm).
The solution was concentrated and left for crystallization.
CH), 6.09 (s, 2H, CH2), 6.41 (d, J = 3.2 Hz, 2H, HFur), 6.82 (s,
1H, HAr), 6.99 (d, J = 3.2 Hz, 2H, HFur), 7.19 (s, 1H, HAr), 7.59
(s, 8H, HAr). Anal. Calcd. for C29H17Br2NO4S: C, 54.83; H, 2.70;
N, 2.20. Found: C, 54.70; H, 2.57; N, 2.35.
7-Bis(5-methyl-2-furyl)methyl-2,3-dihydro-1,4-benzodiox-
in-6-yl isothiocyanate (7e). This compound was obtained
according to the general method in 82% yield as pale beige
needles (hexane), mp 101-102 °C; ir (potassium bromide): 2021,
1506, 1458, 1378, 1309, 1251, 1216, 1199, 1182, 1064, 1022,
939, 891, 804, 796, 786 cm-1; 1H nmr (200 MHz, deuteriochloro-
form): δ 2.26 (s, 6H, CH3), 4.24 (s, 4H, CH2CH2), 5.55 (s, 1H,
CH), 5.89 (d, J = 3.2 Hz, 2H, 4-HFur), 5.95 (d, J = 3.2 Hz, 2H, 3-
HFur), 6.69 (s, 1H, HAr), 6.80 (s, 1H, HAr). Anal. Calcd. for
C20H17NO4S: C, 65.38; H, 4.66; N, 3.81. Found: C, 65.45; H,
4.81; N, 3.74.
2-Bis(5-methyl-2-furyl)methyl-4,5-dimethoxyphenyl iso-
thiocyanate (7f). This compound was obtained according to the
general method in 75% yield as pale beige solid (hexane), mp 88
°C; ir (potassium bromide): 2002, 1604, 1522, 1444, 1351, 1300,
1
1208, 1116, 1010, 922, 837, 794, 776 cm-1; H nmr (300 MHz,
deuteriochloroform): δ 2.26 (s, 6H, CH3), 3.79 (s, 3H, OCH3),
3.87 (s, 3H, OCH3), 5.60 (s, 1H, CH), 5.90 (d, J = 3.2 Hz, 2H, 4-
HFur), 5.96 (d, J = 3.2 Hz, 2H, 3-HFur), 6.69 (s, 1H, HAr), 6.77 (s,
1H, HAr). Anal. Calcd. for C20H19NO4S: C, 65.02; H, 5.18; N
3.79. Found: C, 65.16; H, 5.25; N 3.66.
6-Bis(5-methyl-2-furyl)methyl-1,3-benzodioxol-5-yl iso-
thiocyanate (7a). This compound was obtained according to the
general method in 77% yield as pale beige cubes (hexane), mp
78-79 °C; ir (potassium bromide): 2056, 1618, 1561, 1502,
1483, 1386, 1296, 1249, 1212, 1076, 1023, 938, 882, 832, 776
5-Bromo-2-bis(5-methyl-2-furyl)methylphenyl isothio-
cyanate (7g). This compound was obtained according to the
general method in 75% yield as pale beige solid (hexane), mp
61-62 °C; ir (potassium bromide): 2057, 1909, 1583, 1558,
1475, 1465, 1392, 1378, 1261, 1216, 1166, 1149, 1020, 1000,
1
1
cm-1; H nmr (200 MHz, deuteriochloroform): δ 2.27 (s, 6H,
964, 950, 881, 827, 792, 783, 727 cm-1; H nmr (200 MHz,
CH3), 5.60 (s, 1H, CH), 5.90 (d, J = 3.2 Hz, 2H, 4-HFur), 5.97 (d,
J = 3.2 Hz, 2H, 3-HFur), 5.98 (s, 2H, CH2), 6.67 (s, 1H, HAr), 6.74
(s, 1H, HAr). Anal. Calcd. for C19H15NO4S: C, 64.58; H, 4.28; N,
3.96. Found: C, 64.35; H, 4.40; N, 4.05.
deuteriochloroform) δ 2.26 (s, 6H, CH3), 5.61 (s, 1H, CH), 5.91
(d, J = 3.2 Hz, 2H, 4-HFur), 5.96 (d, J = 3.2 Hz, 2H, 3-HFur), 7.07
(d, J = 8.4 Hz, 1H, HAr), 7.35 (dd, J = 2.0, 8.4 Hz, 1H, HAr), 7.43
(d, J = 2.0 Hz, 1H, HAr). Anal. Calcd. for C18H14BrNO2S: C,
55.68; H, 3.63; N, 3.61. Found: C, 55.75; H, 3.57; N, 3.52.
2-Bis(5-methyl-2-furyl)methylphenyl isothiocyanate (7h).
This compound was obtained according to the general method in
78% yield as pale beige solid (hexane), mp 59 °C; ir (potassium
bromide): 2122, 1613, 1563, 1451, 1216, 1022, 936, 779, 751,
713 cm-1; 1H nmr (300 MHz, deuteriochloroform) δ 2.26 (s, 6H,
CH3), 5.67 (s, 1H, CH), 5.91 (d, J = 3.1 Hz, 2H, 4-HFur), 5.96 (d,
J = 3.1 Hz, 2H, 3-HFur), 7.20-7.27 (m, 4H, HAr). Anal. Calcd. for
C18H15NO2S: C, 69.88; H, 4.89; N, 4.53. Found: C, 69.95; H,
4.76; N, 4.63.
6-Bis(5-ethyl-2-furyl)methyl-1,3-benzodioxol-5-yl isothio-
cyanate (7b). This compound was obtained according to the
general method in 79% yield as pale yellow oil; ir (Nujol): 2123,
1679, 1620, 1560, 1504, 1481, 1242, 1038, 937, 830, 780 cm-1;
1H nmr (360 MHz, deuteriochloroform): δ 1.20 (t, J = 7.6 Hz,
6H, CH2CH3), 2.59 (q, J = 7.6 Hz, 4H, CH2CH3), 5.60 (s, 1H,
CH), 5.90 (d, J = 3.2 Hz, 2H, HFur), 5.95 (s, 2H, CH2), 5.96 (d, J
= 3.2 Hz, 2H, HFur), 6.63 (s, 1H, HAr), 6.72 (s, 1H, HAr). Anal.
Calcd. for C21H19NO4S: C, 66.12; H, 5.02; N, 3.67. Found: C,
66.19; H, 4.91; N, 3.74.

Mar-Apr 2008
Synthesis of 2,4-Difuryl-4H-3,1-benzothiazines via a Furan Ring Migration Reaction
479
2-Bis(5-methyl-2-thienyl)methylphenyl isothiocyanate (7i).
This compound was obtained according to the general method in
85% yield as pale beige solid (hexane), mp 62 °C; ir (potassium
bromide): 2092, 1575, 1479, 1465, 1450, 1377, 1224, 1164,
6,8-Bis[5-(tert-butyl)-2-furyl]-8H-[1,3]dioxolo[4,5-g][3,1]-
benzothiazine (8c). This compound was obtained according to
the general method A in 57% yield as yellow solid (CH2Cl2–
hexane), mp 68 °C; ir (potassium bromide): 1621, 1544, 1479,
1
1033, 935, 802, 757 cm-1; H nmr (300 MHz, deuteriochloro-
1
1366, 1245, 1034, 936, 887, 791, 704 cm-1; H nmr (200 MHz,
form): δ 2.44 (s, 6H, CH3), 6.01 (s, 1H, CH), 6.60 (d, J = 2.2 Hz,
2H, 4-HTh), 6.63 (d, J = 2.2 Hz, 2H, 3-HTh), 7.21-7.27 (m, 3H,
HAr), 7.30-7.34 (m, 1H, HAr). Anal. Calcd. for C18H15NS3: C,
63.31; H, 4.43; N, 4.10. Found: C, 63.39; H, 4.58; N, 3.98.
General procedure for the synthesis of 4H-3,1-benzo-
thiazines 8a-i. Method A. To a solution of isothiocyanate 7 (3
mmol) in 1,4-dioxane (10 mL), HClO4 (70%, 1.0 ml) was added.
The reaction mixture was stirred for 5 hours at r.t. (monitored by
TLC), then poured into water solution NaHCO3 (1%, 50 ml) and
extracted with CH2Cl2 (3 × 30 ml). The organic layer was
separated, dried over anhydrous Na2SO4, the solvent was
evaporated to quarter of volume and diluted with hexane. The
resulting solution was filtered through a pad of silica gel (5-40
µm). The solvent was evaporated and residue was recrystallized
from CH2Cl2–hexane (1:10).
Method B. To a solution of isothiocyanate 7 (3 mmol) in 1,2-
dichloroethane (10 ml), AlCl3 (0.6 g, 4.5 mmol) was added. The
reaction mixture was stirred for 30-60 min at r.t. (monitored by
TLC), then poured into water (200 ml) and extracted with CH2Cl2
(3 × 40 ml). The organic layer was separated, dried over anhydrous
Na2SO4, the solvent was evaporated to quarter of volume and
diluted with hexane. The resulting solution was filtered through a
pad of silica gel (5-40 µm). The solvent was evaporated and
residue was recrystallized from CH2Cl2–hexane (1:10).
6,8-Bis(5-methyl-2-furyl)-8H-[1,3]dioxolo[4,5-g][3,1]benzo-
thiazine (8a). This compound was obtained according to the
general method A in 65% yield as yellow solid (CH2Cl2–
hexane), mp 137-138 °C; ir (potassium bromide): 1548, 1477,
1369, 1248, 1149, 1031, 933, 855, 771 cm-1; 1H nmr (200 MHz,
deuteriochloroform): δ 2.24 (s, 3H, CH3), 2.42 (s, 3H, CH3),
5.18 (s, 1H, CH), 5.74 (d, J = 3.0 Hz, 1H, 3-HFur), 5.76 (d, J =
3.0 Hz, 1H, 4-HFur), 6.00 (s, 2H, CH2), 6.12 (d, J = 3.3 Hz, 1H,
4-HFur), 6.61 (s, 1H, HAr), 6.97 (d, J = 3.3 Hz, 1H, 3-HFur), 7.07
(s, 1H, HAr); 13C nmr (50 MHz, deuteriochloroform): δ 13.7,
14.2, 39.2, 101.6, 106.7, 106.8, 108.1, 108.7, 109.2, 114.4,
117.0, 139.0, 145.7, 146.7, 148.0, 149.6, 150.3, 152.5, 156.7;
ms: m/z 353 (M+, 91), 323 (24), 311 (20), 310 (100), 308 (19),
295 (16), 227 (18), 125 (56), 57 (23), 46 (19), 45 (24), 44 (45),
43 (53), 41 (21), 39 (15). Anal. Calcd. for C19H15NO4S: C, 64.58;
H, 4.28; N, 3.96. Found: C, 64.66; H, 4.19; N, 4.03.
6,8-Bis(5-ethyl-2-furyl)-8H-[1,3]dioxolo[4,5-g][3,1]benzo-
thiazine (8b). This compound was obtained according to the
general method A in 64% yield as yellow solid (CH2Cl2–
hexane), mp 138-139 °C; ir (potassium bromide): 1549, 1477,
1368, 1247, 1192, 1148, 1031, 991, 935, 887, 799, 771 cm-1; 1H
nmr (360 MHz, deuteriochloroform): δ 1.19 (t, J = 7.5 Hz, 3H,
CH2CH3), 1.30 (t, J = 7.5 Hz, 3H, CH2CH3), 2.59 (q, J = 7.5 Hz,
2H, CH2CH3), 2.78 (q, J = 7.5 Hz, 2H, CH2CH3), 5.19 (s, 1H,
CH), 5.77 (d, J = 3.0 Hz, 1H, 3-HFur), 5.79 (d, J = 3.0 Hz, 1H, 4-
HFur), 6.00 (s, 2H, CH2), 6.13 (d, J = 3.4 Hz, 1H, 4-HFur), 6.60 (s,
1H, HAr), 6.99 (d, J = 3.4 Hz, 1H, 3-HFur), 7.07 (s, 1H, HAr); 13C
nmr (50 MHz, deuteriochloroform): δ 11.9, 12.0, 21.4, 21.8,
39.3, 101.6, 105.1, 106.8, 107.0, 108.1, 109.0, 114.5, 116.7,
139.1, 145.8, 146.7, 147.9, 149.5, 150.2, 158.1, 162.3; ms: m/z
381 (M+, 100), 324 (85), 322 (16), 139 (37), 59 (23), 45 (30), 44
(32), 42 (38), 39 (15). Anal. Calcd. for C21H19NO4S: C, 66.12; H,
5.02; N, 3.67. Found: C, 66.01; H, 5.13; N, 3.55.
deuteriochloroform): δ 1.24 (s, 9H, t-Bu), 1.35 (s, 9H, t-Bu),
5.20 (s, 1H, CH), 5.77 (s, 2H, HFur), 6.00 (s, 2H, CH2), 6.11 (d, J
= 3.4 Hz, 1H, 4-HFur), 6.60 (s, 1H, HAr), 6.97 (d, J = 3.4 Hz, 1H,
3-HFur), 7.03 (s, 1H, HAr); 13C nmr (50 MHz, deuteriochloro-
form): δ 29.0 (3C), 29.1 (3C), 32.7, 33.2, 39.4, 101.6, 102.9,
105.1, 106.7, 108.1, 108.6, 114.6, 115.8, 139.2, 146.4, 146.6,
147.8, 149.6, 150.0, 164.4, 168.2; ms: m/z 437 (M+, 100), 422
(38), 352 (68), 350 (18), 55 (22), 45 (30), 44 (24), 43 (38), 39
(15). Anal. Calcd. for C25H27NO4S: C, 68.63; H 6.22; N, 3.20.
Found: C, 68.70; H 6.37; N, 3.11.
6,8-Bis[5-(4-bromophenyl)-2-furyl]-8H-[1,3]dioxolo[4,5-g]-
[3,1]benzothiazine (8d). This compound was obtained
according to the general method A in 48% yield as yellow solid
(CH2Cl2–hexane), mp 180-181 °C; ir (potassium bromide):
1543, 1475, 1369, 1245, 1072, 1027, 924, 886, 825, 791, 771
1
cm-1; H nmr (200 MHz, dimethyl sulfoxide-d6): δ 5.85 (s, 1H,
CH), 6.01 (d, J = 3.1 Hz, 1H, HFur), 6.10 (s, 2H, CH2), 6.82 (d, J
= 3.1 Hz, 1H, HFur), 6.99 (s, 1H, HAr), 7.04 (s, 1H, HAr), 7.22 (d,
J = 3.5 Hz, 1H, HFur), 7.29 (d, J = 3.5 Hz, 1H, HFur), 7.50 (d, J =
8.7 Hz, 2H, HAr), 7.56 (d, J = 8.7 Hz, 2H, HAr), 7.67 (d, J = 8.6
Hz, 2H, HAr), 7.76 (d, J = 8.6 Hz, 2H, HAr); 13C nmr (50 MHz,
deuteriochloroform): δ 39.2, 101.8, 106.7, 107.0, 108.0, 108.3,
110.5, 113.6, 117.0, 121.3, 122.6, 125.3 (2C), 126.2 (2C), 128.7,
129.4, 131.9 (2C), 132.0 (2C), 139.0, 145.2, 147.1, 148.3, 150.7,
152.5, 153.0, 155.9; ms: m/z 637/635/633 (M+, 2/4/2), 605/603/
601 (61/100/64), 452/450 (90/91), 265 (15), 185/183 (21/29), 46
(16), 45 (35), 42 (35), 40 (46). Anal. Calcd. for C29H17Br2NO4S:
C, 54.83; H, 2.70; N, 2.20. Found: C, 54.69; H, 2.78; N, 2.15.
2,4-Bis(5-methyl-2-furyl)-7,8-dihydro-4H-[1,4]dioxino[2,3-g]-
[3,1]benzothiazine (8e). This compound was obtained
according to the general method A in 65% yield as yellow solid
(CH2Cl2–hexane), mp 139-140 °C; ir (potassium bromide):
1573, 1545, 1490, 1310, 1248, 1204, 1063, 1010, 879, 795, 749
1
cm-1; H nmr (200 MHz, deuteriochloroform): δ 2.24 (s, 3H,
CH3), 2.42 (s, 3H, CH3), 4.28 (s, 4H, CH2CH2), 5.20 (s, 1H,
CH), 5.75 (d, J = 3.0 Hz, 1H, 3-HFur), 5.77 (d, J = 3.0 Hz, 1H, 4-
HFur), 6.11 (d, J = 3.4 Hz, 1H, 4-HFur), 6.64 (s, 1H, HAr), 6.97 (d,
J = 3.4 Hz, 1H, 3-HFur), 7.12 (s, 1H, HAr); 13C nmr (50 MHz,
deuteriochloroform): δ 13.7, 14.2, 38.8, 64.4, 64.5, 106.7, 108.6,
109.1, 114.8, 115.3, 116.2, 116.7, 138.0, 142.9, 143.7, 145.9,
149.8, 150.6, 152.4, 156.6; ms: m/z 367 (M+, 100), 336 (17), 324
(41), 268 (18), 125 (22), 44(26), 43(32), 40(16). Anal. Calcd. for
C20H17NO4S: C, 65.38; H, 4.66; N, 3.81. Found: C, 65.43; H,
4.78; N, 3.86.
6,7-Dimethoxy-2,4-bis(5-methyl-2-furyl)-4H-3,1-benzothi-
azine (8f). This compound was obtained according to the
general method A in 68% yield as yellow solid (CH2Cl2–
hexane), mp 154-155 °C; ir (potassium bromide): 1609, 1552,
1508, 1459, 1349, 1257, 1227, 1118, 1016, 951, 868, 789, 748,
725 cm-1; 1H nmr (300 MHz, deuteriochloroform): δ 2.24 (s, 3H,
CH3), 2.43 (s, 3H, CH3), 3.88 (s, 3H, OCH3), 3.95 (s, 3H,
OCH3), 5.23 (s, 1H, CH), 5.68 (d, J = 3.0 Hz, 1H, 3-HFur), 5.77
(d, J = 3.0 Hz, 1H, 4-HFur), 6.12 (d, J = 3.3 Hz, 1H, 4-HFur), 6.64
(s, 1H, HAr), 6.97 (d, J = 3.3 Hz, 1H, 3-HFur), 7.14 (s, 1H, HAr);
13C nmr (50 MHz, deuteriochloroform): δ 13.7, 14.2, 38.9, 56.1
(2C), 106.7, 108.7, 109.1, 109.8, 111.0, 112.5, 116.8, 137.7,
145.5, 148.3, 149.1, 149.7, 150.9, 152.4, 156.6; ms: m/z 369

480
V. T. Abaev, F. A. Tsiunchik, A. V. Gutnov and A. V. Butin
Vol 45
(M+, 90), 354 (15), 338 (100), 326 (56), 268 (21), 244 (16), 243
(22), 125 (58), 95 (33), 46 (17), 45 (20), 43 (36), 42 (23). Anal.
Calcd. for C20H19NO4S: C, 65.02; H, 5.18; N 3.79. Found: C,
64.93; H, 5.30; N 3.65.
[d] Kappe, C. O.; Murphree, S. S.; Padwa, A. Tetrahedron 1997,
14179; [e] Ciufolini, M. A.; Hermann, C. Y. W.; Dong, Q.; Shimizu,
T.; Swaminathan, S.; Xi, N. Synlett 1998, 105; [f] Butin, A. V.;
Abaev, V. T.; Stroganova, T. A.; Gutnov, A. V. In Targets in
Heterocycl. Systems: Chemistry and Properties, Attanasi, O. A.;
Spinelli, D. Ed, Italian Society of Chemistry, Roma, 2001, Vol 5, pp
131-165; [g] Zubkov, F. I.; Nikitina, E. V.; Varlamov, A. V. Usp.
Khim. 2005, 74, 707; Russ. Chem. Rev. (Engl. Transl.) 2005, 74,
639.
[2a] Gimimo, G.; De Stefano, S.; Guerriero, A.; Minale, L.
Tetrahedron Lett. 1975, 1425; [b] Matsumoto, T.; Usui, S. Chem.
Lett. 1978, 105; [c] Nasipuri, D.; Das, G. J. Chem. Soc., Perkin
Trans 1. 1979, 2776.
7-Bromo-2,4-bis(5-methyl-2-furyl)-4H-3,1-benzothiazine
(8g). This compound was obtained according to the general
method A in 59% yield as yellow solid (CH2Cl2–hexane), mp
114 °C; ir (potassium bromide): 1547, 1488, 1360, 1241, 1178,
1
1079, 1024, 924, 759, 733 cm-1; H nmr (200 MHz, deuterio-
chloroform): δ 2.24 (s, 3H, CH3), 2.49 (s, 3H, CH3), 5.27 (s, 1H,
CH), 5.73 (d, J = 3.0 Hz, 1H, 3-HFur), 5.79 (d, J = 3.0 Hz, 1H, 4-
HFur), 6.15 (d, J = 3.5 Hz, 1H, 4-HFur), 7.02 (d, J = 8.2 Hz, 1H,
HAr), 7.06 (d, J = 3.5 Hz, 1H, 3-HFur), 7.38 (dd, J = 1.9, 8.2 Hz,
1H, HAr), 7.74 (d, J = 1.9 Hz, 1H, HAr); 13C nmr (50 MHz,
deuteriochloroform): δ 13.7, 14.3, 38.9, 106.8, 109.0, 109.5,
118.0, 120.2, 122.1, 128.6, 130.1, 130.4, 145.1, 149.2, 149.5,
149.8, 152.8, 157.5; ms: m/z 389/387 (M+, 27/27), 346/344
(15/15), 308 (100), 265 (18), 125 (38), 57 (72), 45 (22), 43 (24),
42 (21). Anal. Calcd. for C18H14BrNO2S: C, 55.68; H, 3.63; N,
3.61. Found: C, 55.81; H, 3.54; N, 3.69.
2,4-Bis(5-methyl-2-furyl)-4H-3,1-benzothiazine (8h). This
compound was obtained according to the general method A in
70% yield as yellow solid (CH2Cl2–hexane), mp 97-98 °C; ir
(potassium bromide): 1604, 1545, 1508, 1446, 1191, 1022, 950,
905, 853, 780, 761, 745 cm-1; 1H nmr (300 MHz, deuteriochloro-
form): δ 2.24 (s, 3H, CH3), 2.44 (s, 3H, CH3), 5.31 (s, 1H, CH),
5.71 (d, J = 3.0 Hz, 1H, 3-HFur), 5.77 (d, J = 3.0 Hz, 1H, 4-HFur),
6.14 (d, J = 3.4 Hz, 1H, 4-HFur), 7.04 (d, J = 3.4 Hz, 1H, 3-HFur),
7.13-7.17 (m, 1H, HAr), 7.23-7.31 (m, 1H, HAr), 7.37-7.45 (m,
1H, HAr), 7.55-7.59 (m, 1H, HAr); 13C nmr (50 MHz, deuterio-
chloroform): δ 13.7, 14.2, 39.3, 106.7, 108.8, 109.3, 117.3,
121.2, 127.3, 127.5, 127.7, 128.9, 143.7, 147.8, 149.7, 150.4,
152.5, 156.9; ms: m/z 309 (M+, 100), 266 (96), 223 (37), 57 (25),
45 (28), 42 (48). Anal. Calcd. for C18H15NO2S: C, 69.88; H,
4.89; N, 4.53. Found: C, 69.95; H, 4.73; N, 4.61.
2,4-Bis(5-methyl-2-thienyl)-4H-3,1-benzothiazine (8i). This
compound was obtained according to the general method A in
45% yield as yellow solid (CH2Cl2–hexane), mp 76 °C; ir
(potassium bromide): 1547, 1440, 1373, 1203, 1052, 894, 805,
761 cm-1; 1H nmr (300 MHz, deuteriochloroform): δ 2.37 (s, 3H,
CH3), 2.54 (s, 3H, CH3), 5.47 (s, 1H, CH), 6.46 (d, J = 2.2 Hz,
1H, 4-HTh), 6.52 (d, J = 2.2 Hz, 1H, 3-HTh), 6.78 (d, J = 2.3 Hz,
1H, 4-HTh), 7.17-7.20 (m, 1H, HAr), 7.24-7.29 (m, 1H, HAr),
7.37-7.42 (m, 1H, HAr), 7.48-7.51 (m, 1H, HAr), 7.55 (d, J = 2.3
Hz, 1H, 3-HTh); 13C nmr (50 MHz, deuteriochloroform): δ 15.4,
16.0, 41.8, 123.5, 124.8, 125.7, 126.3, 126.9, 127.3, 127.6,
128.8, 130.4, 140.3, 141.2, 142.5, 143.5, 146.3, 151.9; ms: m/z
341 (M+, 100), 326 (57), 308 (37), 57 (17), 55 (16), 46 (17), 45
(29), 44 (48), 43 (38), 41 (16). Anal. Calcd. for C18H15NS3: C,
63.31; H, 4.43; N, 4.10. Found: C, 63.42; H, 4.33; N, 4.04.
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Acknowledgement. Financial support was provided by the
Russian Foundation of Basic Research (grant 07-03-00352-a)
and Bayer HealthCare AG (Germany). The authors would like to
emphasis their special thanks to Dr. V. E. Zavodnik for the
accomplishment of X-ray analysis.
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[21] Crystal data of compound 8e: C20H17NO4S, triclinic, space
group P-1; a = 8.311(2) Å, b = 10.194(2) Å, c = 11.232(2) Å, α =
90.02(3)o, β = 98.44(3)o, γ = 112.23(3)o, V = 869.7(3) Å3, Z = 2,
Dcalcd = 1.403 Mg/m3, F(000) = 384; 2894 reflections collected, 2249
unique (Rint = 0.0125); final R indices (2249 observed collections I >
2σI): R1 = 0.0280, wR2 = 0.0793; final R indices (all data): R1 =
0.0280, wR2 = 0.0793. Crystallographic data (excluding structure
factors) for the structure in this article have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication number CCDC 642230. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax; +44(0)-1223-336033 or e-mail:
deposit@ccdc.cam.ac.uc]. Each request should be accompanied by
the complete citation of this paper.