Synthesis and reactions of 3-alkylsulfanyl-1,3-dihydro-2,1-benzisothiazole 2,2-dioxides

Article abstract of DOI:10.1016/j.tet.2005.07.015

Alkyl- and arylsulfanylation of 1,3-dihydro-2,1-benzisothiazole 2,2-dioxides (benzosultams) 1a-c and pyridosultam 1d with dialkyl and diaryl disulfides provides dithioacetals of 2-aminobenzaldehydes 6-13. 1,3-Dimethylbenzosultam 19 with disulfides forms 3-alkyl(aryl)sulfanyl-1,3- dimethylbenzosultams 20-22 that undergo thermal extrusion of SO₂ followed by a [1,5] sigmatropic hydrogen shift in the intermediate aza-ortho-xylylene leading to 1-arylvinyl sulfides 24-26. Tandem alkylation-sulfanylation of benzo- and pyridosultams 1a-d with 4-bromobutyl thiocyanate gives tetrahydrothiopyrano-spiro-benzosultams 27-30 that, after extrusion of SO₂ and [1,5] hydrogen shift, form 2-aryl-5,6-dihydro- 4H-thiopyrans 32-35. Alkylation of pyridosultam 1d with 3-chloropropyl thiocyanate leads directly to 2-pyrido-3,4-dihydrothiophene derivative 37.

Full text of DOI:10.1016/j.tet.2005.07.015

Tetrahedron 61 (2005) 8848–8854
Synthesis and reactions of 3-alkylsulfanyl-1,3-dihydro-2,1-
benzisothiazole 2,2-dioxides
*
Helena Modrzejewska and Krzysztof Wojciechowski
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, PO Box 58, 01-224 Warszawa 42, Poland
Received 19 May 2005; revised 28 June 2005; accepted 7 July 2005
Available online 26 July 2005
Abstract—Alkyl- and arylsulfanylation of 1,3-dihydro-2,1-benzisothiazole 2,2-dioxides (benzosultams) 1a–c and pyridosultam 1d with
dialkyl and diaryl disulfides provides dithioacetals of 2-aminobenzaldehydes 6–13. 1,3-Dimethylbenzosultam 19 with disulfides forms
3-alkyl(aryl)sulfanyl-1,3-dimethylbenzosultams 20–22 that undergo thermal extrusion of SO2 followed by a [1,5] sigmatropic hydrogen shift
in the intermediate aza-ortho-xylylene leading to 1-arylvinyl sulfides 24–26. Tandem alkylation–sulfanylation of benzo- and pyridosultams
1a–d with 4-bromobutyl thiocyanate gives tetrahydrothiopyrano-spiro-benzosultams 27–30 that, after extrusion of SO2 and [1,5] hydrogen
shift, form 2-aryl-5,6-dihydro-4H-thiopyrans 32–35. Alkylation of pyridosultam 1d with 3-chloropropyl thiocyanate leads directly to
2-pyrido-3,4-dihydrothiophene derivative 37.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Methods of introduction of thio substituents into position-a
to electron-withdrawing groups deal with reactions of the
corresponding carbanions with sulfanylating agents, such as
S-alkyl methanethiosulfonates,8–10 dialkyl disulfides,11 or
organic thiocyanates.12 Numerous reactions of this type
were performed under phase-transfer catalysis conditions
employing both solid–liquid10 and liquid–liquid12 systems.
Direct monosulfanylation of a-sulfonyl carbanions with
dimethyl disulfide in the presence of sodium hydride in
DMSO has also been described.13
Thermal extrusion of sulfur dioxide from 2,1-benzisothiazo-
line 2,2-dioxides (benzosultams)1 provides 6-methylene-
cyclohexa-2,4-dien-1-imines (ortho-quinone methide
imines, aza-ortho-xylylenes).2 These reactive 1-azadienes
undergo Diels–Alder reaction leading to 1,2,3,4-tetra-
hydroquinoline derivatives,3 undergo [1,5] sigmatropic
hydrogen shift leading to Schiff bases or 2-vinylanilines,4
or add nucleophiles to form 2-aminobenzyl derivatives.5,6
We were interested in how replacement of the hydrogen
atoms in the exocyclic methylene group with heteroatoms
would influence the reaction course of aza-ortho-xylylenes.
In one of our previous papers, we described the extrusion of
SO2 from 3,3-dichlorobenzosultams and trapping of the
generated 6-(dichloromethylene)cyclohexa-2,4-dien-1-
alkylimines with amines.7
Our attempts to employ these base-solvent systems to obtain
3-(phenylsulfanyl)benzosultam under analogous conditions
failed. In the reaction of equimolar amounts of benzosultam
1a and diphenyl disulfide in the presence of NaH in DMSO,
the starting materials were completely consumed and a
complex inseparable mixture of products, probably origi-
nating from mono- and di-sulfenylated benzosultams, was
formed.
In this paper, we present results of our studies on the
introduction of alkyl-(or aryl) thio substituents into the
3-position of benzosultams and the use of the obtained
products as precursors of practically unknown aza-ortho-
xylylenes bearing alkylsulfanyl substituents in the exocyclic
methylene group.
Attempts to obtain 3,3-di(phenylsulfanyl)benzosultam 3
from benzosultam 1a and 2 mol of diphenyl disulfide under
standard phase-transfer catalysis conditions [50% NaOH,
tetrabutylammonium bromide (TBAB)] were also unsuc-
cessful (Scheme 1). Similar results were obtained using
other base-solvent systems such as NaH in DMSO or
t-BuOK in DMF. In these instances GC–MS analysis of the
reaction mixture has revealed presence of products whose
molecular mass corresponded to an addition of diphenyl
Keywords: Benzosultams; Spiro compounds; Alkylsulfanylation; Extru-
sion; [1,5] Sigmatropic hydrogen shift; Aza-ortho-xylylenes; Dihydrothio-
pyrans; Phase-transfer catalysis; Sulfides; Disulfides.
*
Corresponding author. Tel.: C48 22 3432101; fax: C48 22 6326681;
e-mail: kris@icho.edu.pl
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.015

H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
8849
decomposition of relatively unstable a-alkylthiobenzyl
sulfones occurred at temperature 130–170 8C.13
The alkyl- and arylsulfanylation of the tertiary carbanion of
1,3-dimethylbenzosultam 19 with dimethyl and diaryl
disulfides in the presence of solid powdered NaOH in
dimethylsulfoxide proceeded smoothly, and the expected
3-methylsulfanyl- and 3-arylsulfanylbenzosultams (20–22)
were obtained (Scheme 3). Heating of 3-methyl-3-sulfanyl
derivatives in boiling chlorobenzene (140 8C) results in
extrusion of SO2 and the intermediate aza-ortho-xylylenes
23 undergo [1,5]-sigmatropic hydrogen shift to give
1-arylvinyl sulfides 24–26 in good yields.
Scheme 1.
disulfide to the intermediate azaxylylene. Results of these
attempts suggested low thermal stability of the expected
mono- and/or bis-sulfenylated products. When this reaction
was run in the presence of solid K2CO3 and tetrabutyl-
ammonium hydrogensulfate (TBAHS) as a phase-transfer
catalyst in boiling acetonitrile (80 8C), TLC analysis has
revealed the presence of one product. The reaction was
complete in 24 h, and the dithioacetal of 2-aminobenzalde-
hyde 6 was isolated in 37% yield. Other benzosultams
reacted similarly giving the dithioacetals 7–13 in moderate
to good yields.
Scheme 3.
We next, investigated alkylation–sulfanylation of the
sultams 1a–d with 4-bromobutyl thiocyanate under phase-
transfer catalysis conditions employing 50% aqueous NaOH
and tetrabutylammonium bromide (TBAB). The expected
spiro compounds 25–28 were obtained in good yields.
Thermal extrusion of SO2 from the spiro compounds
proceeded smoothly and the intermediate azaxylylenes 31
underwent [1,5] sigmatropic hydrogen shift to form novel
6-aryl-3,4-dihydro-2H-thiopyrans 32–35 in good yields
(Scheme 4).
Plausible routes for the formation of these products are
shown in the Scheme 2. The first one (A) involves extrusion
of SO2 from the initially formed 3-methylthio derivative 14
to form azaxylylene 15, which intercepts the alkylthiolate
anion generated from the disulfide. Another route (B) may
follow heterolytic fission of the C–SO2 bond leading to a
zwitterionic species 16 isomeric to benzoxathiazine 17.
Both 16 and 17 can intercept a thiolate anion, with a
consecutive elimination of SO2 to form dithioacetal 6. Both
of these routes involve thermal instability of the inter-
mediate monosulfanylated products. The reported thermal
Attempts to obtain analogous spiro compounds, spiro-2-
thietanes and spiro-2-tetrahydrothiophenes, in reactions of
benzosultams 1a–c with 2-chloroethyl and 3-chloropropyl
thiocyanates were unsuccesful. These reactions led to
complex mixtures of products, from which isolation of
expected spiro compounds proved impossible. Only in the
Scheme 2.

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H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
4. Experimental
4.1. General
Melting points are uncorrected. 1H and 13C NMR and
spectra were obtained on a Varian Mercury 400 BB (400
and 100 MHz, respectively) instrument in CDCl3 with TMS
as internal standard. Coupling constants J are given in Hz.
IR spectra were recorded with Perkin Elmer 2000 FTIR
instrument. Mass spectra (electron impact, 70 eV) were
obtained on AMD 604 (AMD Intectra GmbH, Germany)
instrument. HRMS were measured in the presence of
perfluorokerosene as the reference compound. Elemental
analyses were obtained using a Elementar Vario EL III
instrument. Column chromatography was performed using
silica gel 240–400 mesh (Merck). Benzosultams 1a–c and
19 were obtained from the corresponding N-alkyl-2-chloro-
N-(alkanesulfonyl)anilines following the known pro-
cedures.15,16 Pyridosultam 1d was prepared according to
the earlier described procedure.14
Scheme 4.
4.2. Reactions of benzosultams with disulfides. General
procedure
case of alkylation of pyridosultam 1d with 3-chloropropyl
thiocyanate dihydrothiophene derivative 37 was obtained in
moderate yield (Scheme 5). No intermediate spiro sultam 36
was isolated. This is probably due to an elimination of SO2
facilitated by an antiperiplanar configuration of the C–H and
C–SO2 bonds in the intermediate spiro compound 36.
Similar elimination was observed earlier during alkylation
of pyridosultam 1d with 1,2-bis(bromomethyl)benzene.14
Sultam 1a–d (1 mmol), disulfide 2 (1.1 mmol), K2CO3
(0.5 g, 4 mmol) and tetrabutylammonium hydrogensulfate
(34 mg, 0.1 mmol) were heated in acetonitrile (5 mL) at
reflux under an argon atmosphere until the starting material
disappeared (6–40 h, TLC control). The reaction mixture
was then poured into water (50 mL), and product was
extracted with dichloromethane (3!25 mL). The combined
extracts were washed with water, dried with Na2SO4 and
evaporated. Products were purified by column chromato-
graphy (silica gel–hexane/ethyl acetate 2:1 for 6–11 or
hexane/ethyl acetate 1:2 for 12 and 13). The following
products were obtained:
4.2.1. {2-[Bis-(methylsulfanyl)methyl]phenyl}methyl-
amine (6). Oil. 1H NMR (400 MHz): dZ2.08 (s, 6H),
2.89 (s, 3H), 4.50 (br s, 1H), 4.89 (s, 1H), 6.71 (d, JZ
8.1 Hz, 1H), 6.73 (ddd, JZ7.6, 7.4, 1.1 Hz, 1H), 7.23 (ddd,
JZ8.1, 7.4, 1.5 Hz, 1H), 7.30 (dd, JZ7.6, 1.5 Hz, 1H). 13C
NMR (100 MHz): dZ14.99, 30.70, 53.65, 111.09, 116.65,
121.48, 128.70, 129.01, 146.76. IR (KBr, cmK1) n: 3395,
2980, 2915, 2813, 1724, 1657, 1602, 1581, 1512, 1462,
1425, 1315, 1273, 1171, 1063, 1044, 961, 748. MS (EI
70 eV, m/z, %): 213 (MC, 9), 166 (70), 150 (7), 118 (100),
91 (34). HRMS for C10H15NS2 calcd 213.0646, found
213.0656. Elemental analysis for C10H15NS2 (213.36) calcd
C 56.30, H 7.09, N 6.56, found C 56.34, H 6.95, N 6.50.
Scheme 5.
3. Conclusion
In conclusion, the reaction course of the 2,1-benzisothiazo-
line 2,2-dioxides (benzosultams) with sulfanylating agents
depends on the structure of both starting materials. The
alkylsulfanylation of benzosultams with dialkyl and diaryl
disulfides in the presence of potassium carbonate in
acetonitrile leads directly to 2-aminobenzaldehyde dithio-
acetal derivatives. 3-Alkylbenzosultams undergo 3-alkyl-
(aryl)sulfanylation to form stable 3-alkyl-3-sulfanyl deriva-
tives, that can transform into 1-arylvinyl sulfides via thermal
extrusion of SO2 followed by a [1,5] hydrogen shift in the
intermediate aza-ortho-xylylene. Spirobenzosultams
obtained in the reaction of benzosultams with 1,u-haloalkyl
thiocyanates transform into 2-aryldihydrothiopyrans and
2-aryldihydrothiophenes.
4.2.2. {2-[Bis-(phenylsulfanyl)methyl]phenyl}methyl-
amine (7). Oil. 1H NMR (400 MHz): dZ2.93 (s, 3H),
4.60 (br s, 1H), 5.54 (s, 1H), 6.58 (dt, JZ7.4, 1.0 Hz, 1H),
6.71 (d, JZ7.4 Hz, 1H), 7.16–7.24 (m, 8H), 7.31–7.35
(m, 4H). 13C NMR (100 MHz): dZ30.93, 58.21, 111.27,
117.09, 122.14, 127.69, 128.80, 129.16, 129.33, 132.15,
134.51, 146.60. IR (KBr) n: 3363, 3072, 3057, 2813, 1656,
1603, 1580, 1510, 1479, 1463, 1438, 1425, 1315, 1170,
1086, 1066, 1024, 742, 689. MS (EI 70 eV, m/z, %): 337
(MC, 1), 228 (57), 150 (4), 118 (100), 91 (21). HRMS for
C20H19NS2 calcd 337.0959, found 337.0961. Elemental

H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
8851
analysis for C20H19NS2 (337.49) calcd C 71.18, H 5.67, N
4.15, found C 71.27, H 5.61, N 4.21.
4.2.7. {2-[Bis-(methylsulfanyl)methyl]pyridin-3-yl}-
methylamine (12). Colorless needles. Mp 72–73 8C (from
cyclohexane). H NMR (400 MHz): dZ2.10 (s, 6H), 2.89
1
(d, JZ5.1 Hz, 3H), 4.56 (br s, 1H), 5.01 (s, 1H), 6.96 (dd,
JZ8.2, 1.3 Hz, 1H), 7.13 (dd, JZ8.3, 4.7 Hz, 1H), 7.94 (dd,
JZ4.7, 1.3 Hz, 1H). 13C NMR (100 MHz): dZ13.72,
30.15, 56.52, 117.25, 123.50, 136.66, 142.28. IR (KBr) n:
3398, 2992, 2913, 2816, 1582, 1504, 1460, 1416, 1401,
1322, 1310, 1292, 1247, 1217, 1147, 1093, 964, 788, 762,
719, 652. MS (EI 70 eV, m/z, %): 214 (MC, 9), 167 (100),
151 (98), 132 (10), 119 (63), 92 (32). HRMS for C9H14N2S2
calcd 214.0598, found 214.0607. Elemental analysis for
C9H14N2S2 (214.34) calcd C 50.43, H 6.58, N 13.07, found
C 50.24, H 6.56, N 12.97.
4.2.3. {2-[Bis-(phenylsulfanyl)methyl]phenyl}isopropyl-
amine (8). Oil. 1H NMR (400 MHz): dZ1.29 (d, JZ
6.2 Hz, 6H), 3.72 (sept, JZ6.2 Hz, 1H), 4.35 (br s, 1H), 5.48
(s, 1H), 6.54 (dt, JZ7.4, 1.1 Hz, 1H), 6.71 (d, JZ8.0 Hz,
1H), 7.14 (ddd, JZ8.3, 7.4, 1.5 Hz, 1H), 7.20–7.26 (m, 7H),
7.32–7.36 (m, 4H). 13C NMR (100 MHz): dZ22.98, 44.14,
58.55, 112.25, 116.48, 122.00, 127.65, 128.80, 129.16,
129.37, 132.12, 134.80, 144.88. IR (KBr) n: 3353, 3059,
2965, 2928, 1601, 1582, 1511, 1479, 1461, 1438, 1383,
1365, 1316, 1259, 1176, 1086, 1067, 1052, 1025, 742, 689.
MS (EI 70 eV, m/z, %): 365 (MC, 0.5), 256 (42), 162 (3),
146 (100), 131 (24), 110 (4). HRMS for C22H23NS2 calcd
365.1272, found 365.1288. Elemental analysis for
C22H23NS2 (365.53) calcd C 72.28, H 6.34, N 3.83, found
C 72.25, H 6.46, N 3.83.
4.2.8. {2-[Bis-(phenylsulfanyl)-methyl]pyridin-3-yl}-
methylamine (13). Colorless plates. Mp 94–95 8C (from
1
cyclohexane). H NMR (400 MHz): dZ2.92 (s, 3H), 4.86
(br s, 1H), 5.87 (br s, 1H), 6.96 (d, JZ7.8 Hz, 1H), 7.09 (dd,
JZ7.8, 4.3 Hz, 1H), 7.20–7.26 (m, 6H), 7.39–7.45 (m, 4H),
7.75 (d, JZ4.3 Hz, 1H). 13C NMR due to dynamic
phenomena no legible spectrum recordable under standard
conditions. IR (KBr) n: 3362, 3339, 3054, 2817, 1583, 1437,
1425, 1321, 1292, 1250, 1162, 1086, 1023, 881, 794, 734,
688. MS (EI 70 eV, m/z, %): 338 (MC, 0.5), 229 (100), 195
(96), 119 (55), 110 (13), 92 (25). HRMS for C19H18N2S2
calcd 338.0911, found 338.0909. Elemental analysis for
C19H18N2S2 (338.35) calcd C 67.42, H 5.36, N 8.28, found
C 67.20, H 5.41, N 8.25.
4.2.4. {2-[Bis-(phenylsulfanyl)methyl]-4-methylphenyl}-
methylamine (9). Oil. H NMR (400 MHz): dZ2.14 (s,
1
3H), 2.89 (s, 3H), 4.40 (br s, 1H), 5.53 (s, 1H), 6.62 (d, JZ
8.1 Hz, 1H), 7.00 (dd, JZ8.1, 2.1 Hz, 1H), 7.03 (br s, 1H),
7.19–7.26 (m, 6H), 7.30–7.36 (m, 4H). 13C NMR
(100 MHz): dZ20.26, 31.13, 57.87, 111.49, 122.49,
127.58, 128.77, 129.36, 129.60, 129.74, 131.99, 134.70,
144.35. IR (KBr) n: 3366, 3057, 2917, 2873, 2810,
1653, 1616, 1579, 1513, 1478, 1438, 1310, 1227, 1168,
1086, 1066, 1024, 943, 808, 739, 689. MS (EI 70 eV, m/z,
%): 351 (MC, 2), 242 (86), 164 (4), 132 (100), 117 (27), 105
(13). HRMS for C21H21NS2 calcd 351.1115, found
351.1123.
4.3. Reactions of 1,3-dimethylbenzosultam 19 with
dialkyl(aryl) disulfides. General procedure
To a solution of 1,3-dimethylbenzosultam (400 mg,
2 mmol) and dialkyl(aryl) disulfide (2 mmol) in DMSO
(5 mL), powdered sodium hydroxide (1.0 g, 25 mmol) was
added in one portion. The reaction mixture was stirred under
argon for 30 min at room temperature. The reaction mixture
was then poured into water (50 mL) and extracted with ethyl
acetate (3!25 mL). The combined extracts were washed
with water and dried with Na2SO4. The products were
purified by column chromatography on silica gel (hexane/
ethyl acetate 4:1) and crystallized from ethanol. The
following compounds were obtained:
4.2.5. {2-[Bis-(methylsulfanyl)methyl]-4-methylphenyl}-
methylamine (10). Oil. H NMR (400 MHz): dZ2.09 (s,
1
6H), 2.26 (s, 3H), 2.87 (s, 3H), 4.87 (s, 1H), 6.63 (d, JZ
8.2 Hz, 1H), 7.04 (dd, JZ8.2, 1.8 Hz, 1H), 7.12 (d, JZ
1.8 Hz, 1H). 13C NMR (100 MHz): dZ15.02, 20.43, 30.97,
53.60, 111.39, 121.81, 125.92, 129.18, 129.41, 144.47.
IR (KBr) n: 3392, 3361, 2979, 2915, 2809, 1654, 1615,
1578, 1514, 1433, 1311, 1266, 1171, 960, 807. MS (EI
70 eV, m/z, %): 227 (12), 180 (65), 164 (7), 132 (100), 117
(33), 105 (16), 91 (4). HRMS for C11H17NS2 calcd
227.0802, found 227.0795. Elemental analysis for
C11H17NS2 (227.37) calcd C 58.10, H 7.53, N 6.16, found
C 58.11, H 7.43, N 6.22.
4.3.1. 1,3-Dimethyl-3-methylsulfanyl-1,3-dihydro-2,1-
benzisothiazole 2,2-dioxide (20). White solid. Mp
63–64 8C. 1H NMR (400 MHz): dZ1.94 (s, 3H), 2.09
(s, 3H), 3.17 (s, 3H), 6.75 (d, JZ8.0 Hz, 1H), 7.09 (dt, JZ
7.5, 1.0 Hz, 1H), 7.30–7.38 (m, 2H). 13C NMR (100 MHz):
dZ13.62, 22.53, 27.09, 69.05, 109.48, 122.46, 124.36,
125.17, 130.05, 140.20. IR (KBr) n: 2929, 1602, 1482, 1467,
1445, 1318, 1306, 1191, 1153, 1121, 1082, 1064, 1037, 847,
753. MS (EI 70 eV, m/z, %): 243 (MC, 8), 197 (1), 196 (1),
179 (10), 164 (100), 149 (6), 132 (11), 130 (11), 117 (13).
HRMS for C10H13NO2S2 calcd 243.0388, found 243.0376.
Elemental analysis for C10H13NO2S2 (243.34) calcd C
49.35, H 5.39, N 5.76, found C 49.58, H 5.27, N 5.75.
4.2.6. {2-[Bis-(methylsulfanyl)methyl]phenyl}isopropyl-
amine (11). Oil. 1H NMR (400 MHz): dZ1.26 (d, JZ
6.3 Hz, 6H), 2.07 (s, 6H), 3.69 (sept, JZ6.3 Hz, 1H), 4.29
(br s, 1H), 4.86 (s, 1H), 6.66 (ddd, JZ7.4, 7.4, 1.1 Hz, 1H),
6.72 (br d, JZ8.1 Hz, 1H), 7.18 (ddd, JZ8.1, 7.4, 1.5 Hz,
1H), 7.28 (dd, JZ7.4, 1.5 Hz, 1H). 13C NMR (100 MHz):
dZ14.97, 28.86, 44.07, 53.84, 112.17, 116.08, 121.13,
128.86, 129.06, 145.06. IR (KBr) n: 3378, 2967, 2916, 2869,
1601, 1582, 1513, 1458, 1435, 1383, 1365, 1319, 1261,
1209, 1176, 1156, 1053, 960, 871, 746. MS (EI 70 eV, m/z,
%): 241 (MC, 8), 211 (2) 194 (50), 169 (4), 146 (100), 136
(11), 131 (43), 117 (4), 105 (5). HRMS for C12H19NS2 calcd
241.0959, found 241.0970. Elemental analysis for
C12H19NS2 (241.41) calcd C 59.70, H 7.94, N 5.80, found
C 59.78, H 7.80, N 6.05.
4.3.2. 1,3-Dimethyl-3-phenylsulfanyl-1,3-dihydro-2,1-
benzisothiazole 2,2-dioxide (21). White solid. Mp 96–
1
97 8C. H NMR (400 MHz): dZ1.98 (s, 3H), 2.88 (s, 3H),
6.48 (d, JZ8.0 Hz, 1H), 7.05 (dt, JZ7.7, 1.1 Hz, 1H),

8852
H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
7.16–7.22 (m, 2H), 7.26 (dt, 7.7, 1.4 Hz, 1H), 7.29–7.34 (m,
2H), 7.37–7.39 (m, 2H). 13C NMR (100 MHz): dZ20.23,
26.92, 71.60, 109.37, 122.19, 124.38, 125.87, 128.31,
128.52, 129.95, 130.02, 137.39, 139.86. IR (KBr) n: 3072,
1602, 1470, 1437, 1317, 1281, 1185, 1156, 1122, 1084,
1025, 841, 825, 762, 743, 691. MS (EI 70 eV, m/z, %): 305
(MC, 6), 241 (30), 208 (5), 197 (14), 196 (31), 164 (100),
152 (11), 148 (19), 136 (11), 132 (62), 130 (22), 118 (20),
117 (32). HRMS for C15H15NO2S2 calcd 305.0544, found
305.0545. Elemental analysis for C15H15NO2S2 (305.41)
calcd C 58.99, H 4.95, N 4.59, found C 58.98, H 4.80, N
4.56.
70 eV, m/z, %): 241 (MC, 27), 164 (72), 149 (3), 132 (100),
131 (16), 130 (30), 117 (68), 115 (16), 105 (13), 99 (52).
HRMS for C15H15NS calcd 241.0925, found 241.0918.
4.4.3. {2-[1-(4-Chlorophenylsulfanyl)vinyl]phenyl}-
1
methylamine (26). Oil. H NMR (400 MHz): dZ2.84 (s,
3H), 4.60 (s, 1H), 5.22 (s, 1H), 5.31 (s, 1H), 6.54–6.75 (m,
2H), 7.05–7.30 (m, 6H). 13C NMR (100 MHz): dZ30.64,
109.88, 114.75, 116.20, 123.60, 129.19, 129.71, 130.06,
131.36, 134.58, 135.27, 143.71, 146.17. IR (KBr) n: 3424,
2916, 2815, 1629, 1600, 1575, 1513, 1475, 1424, 1388,
1314, 1260, 1170, 1093, 1012, 821, 747. MS (EI 70 eV, m/z,
%): 275 (MC, 28), 242 (7), 164 (46), 132 (100), 131 (11),
130 (20), 117 (37). HRMS for C15H14ClNS calcd 275.0536,
found 275.0539.
4.3.3. 1,3-Dimethyl-3-(4-chlorophenylsulfanyl)-1,3-di-
hydro-2,1-benzisothiazole 2,2-dioxide (22). White solid.
1
Mp 93–94 8C. H NMR (400 MHz): dZ1.98 (s, 2H), 2.89
(s, 3H), 6.50 (br d, JZ7.8 Hz, 1H), 7.07 (dt, JZ7.8, 1.0 Hz,
1H), 7.13–7.19 (m, 2H), 7.25–7.35 (m, 4H). 13C NMR
(100 Hz): dZ19.99, 26.81, 71.52, 109.41, 122.30, 124.31,
125.50, 126.97, 128.47, 130.24, 136.60, 138.54, 139.85. IR
(KBr) n: 3076, 2981, 2931, 1603, 1570, 1476, 1469, 1321,
1298, 1273, 1183, 1157, 1123, 1079, 1030, 1016, 832, 810,
770. MS (EI 70 eV, m/z, %): 339 (MC, 7), 275 (22), 196
(74), 164 (100), 148 (36), 132 (95), 130 (34), 117 (43), 109
(10). HRMS for C15H14NO2S2Cl calcd 339.0155, found
339.0163. Elemental analysis for C15H14NO2S2Cl (339.86)
calcd C 53.01, H 4.15, N 4.12, found C 52.97, H 4.19, N
4.09.
4.5. Synthesis of spiro compounds 27–30. General
procedure
Sultam 1a–d (2 mmol), 4-bromobutyl thiocyanate
(2.2 mmol), tetrabutylammonium bromide (32 mg,
0.1 mmol) in toluene (5 mL) were stirred vigorously with
50% aqueous NaOH (10 mL) at room temperature under
argon. The progress of the reaction was monitored by TLC
(30–90 min). Then the reaction mixture was poured into
water (50 mL) and the product was extracted with
dichloromethane (3!25 mL). The combined extracts were
washed with water and dried over Na2SO4. After
evaporation of solvent the product was purified by column
chromatography (hexane/ethyl acetate 2:1) and crystallized
from ethanol. The following compounds were obtained:
4.4. Extrusion of SO2 from 1,3-dimethyl-3-alkyl(aryl)
sulfanylbenzosultam. General procedure
Benzosultam (20–22, 1 mmol) was heated in chlorobenzene
(5 mL) at reflux. The progress of the reaction was monitored
by TLC (hexane/ethyl acetate 4:1, 1.5–6 h). The reaction
mixture was then subjected to column chromatography. The
chlorobenzene was eluted with hexane/ethyl acetate (50:1)
and then product with hexane/ethyl acetate 2:1. The
following compounds were obtained:
4.5.1. 1-Methyl-1,3-dihydro-2,1-benzisothiazole-3-spiro-
20-tetrahydrothiopyran 2,2-dioxide (27). White solid. Mp
122–123 8C. H NMR (400 MHz): dZ1.82–2.10 (m, 3H),
1
2.14–2.22 (m, 1H), 2.37 (ddd, JZ14.3, 13.2, 3.7 Hz, 1H),
2.55 (ddd, JZ14.0, 3.2, 2.9 Hz, 1H), 2.70 (ddd, JZ14.3,
3.1, 2.9 Hz, 1H), 3.19 (s, 3H), 3.57 (ddd, JZ13.5, 12.7,
2.7 Hz, 1H), 6.74 (br d, JZ8.0 Hz, 1H), 7.05 (ddd, JZ7.8,
7.7, 1.1 Hz, 1H), 7.28 (dd, JZ8.0, 1.4 Hz, 1H), 7.33 (ddd,
JZ8.0, 7.7, 1.4 Hz, 1H). 13C NMR (100 MHz): dZ22.78,
25.29, 27.57, 28.12, 31.45, 67.68, 109.86, 122.44, 124.37,
125.92, 130.20, 140.06. IR (KBr) n: 2943, 2922, 1603, 1483,
1470, 1311, 1190, 1152, 1134, 1066, 1029, 839, 752. MS
(EI 70 eV, m/z, %): 269 (MC, 0.5), 205 (53), 176 (49), 162
(12), 144 (38), 130 (100), 117 (17). HRMS for
C12H15NO2S2 calcd 269.0544, found 269.0557.
4.4.1. Methyl-[2-(1-methylsulfanylvinyl)phenyl]amine
1
(24). Oil. H NMR (400 MHz): dZ2.23 (s, 3H), 2.85 (s,
3H), 5.17 (s, 1H), 5.24 (s, 1H), 6.62 (br d, JZ8.2 Hz, 1H),
6.68 (dt, JZ7.5, 1.0 Hz, 1H), 7.10 (dd, JZ7.5, 1.5 Hz, 1H),
7.23 (ddd, JZ8.2, 7.5, 1.5 Hz, 1H). 13C NMR (100 MHz):
dZ15.31, 30.62, 109.75, 109.85, 116.23, 124.72, 129.54,
129.65, 144.19, 146.17. IR (KBr) n: 3420, 2982, 2917, 2814,
1605, 1589, 1578, 1511, 1460, 1425, 1315, 1290, 1259,
1212, 1169, 1077, 1038, 858, 747. MS (EI 70 eV, m/z, %):
179 (MC, 33), 164 (100), 149 (10), 132 (27), 130 (26),
117 (39), 103 (7). HRMS for C10H13NS calcd 179.0769,
found 179.0772. Elemental analysis for C10H13NS (179.28)
calcd C 66.99, H 7.31, N 7.81, found C 66.96, H 7.35, N
7.61.
4.5.2. 1,5-Dimethyl-1,3-dihydro-2,1-benzisothiazole-3-
spiro-20-tetrahydrothiopyran 2,2-dioxide (28). Pale
1
yellow solid. Mp 110–111 8C. H NMR (400 MHz): dZ
1.75–2.20 (m, 4H), 2. 34 (s, 3H), 2. 36 (ddd, JZ16.9, 13.2,
3.5 Hz, 1H), 2.50–2.57 (m, 1H), 2.69 (dt, JZ14.2, 3.2 Hz,
1H), 3.17 (s, 3H), 3.57 (ddd, JZ13.4, 12.8, 2.9 Hz, 1H),
6.65 (d, JZ8.1 Hz, 1H), 7.09 (dd, JZ1.7, 0.7 Hz, 1H), 7.13
(ddd, JZ8.1, 1.7, 0.7 Hz, 1H). 13C NMR (100 MHz): dZ
20.97, 22.78, 25.35, 28.09, 28.11, 31.41, 67.75, 110.07,
124.86, 125.93, 130.66, 132.22, 137.87. IR (KBr) n: 2944,
2919, 2862, 1614, 1492, 1464, 1445, 1428, 1312, 1186,
1162, 1132, 839, 819. MS (EI 70 eV, m/z, %): 283 (MC, 4),
219 (62), 204 (12), 190 (66), 176 (15), 158 (34), 144 (100),
130 (12), 115 (11). HRMS for C13H17NO2S2 calcd
283.0701, found 283.0693. Elemental analysis for
4.4.2. Methyl-{2-[1-(phenylsulfanyl)vinyl]phenyl}amine
(25). Oil. 1H NMR (200 MHz): dZ2.87 (s, 3H), 4.60 (br s,
1H), 5.16 (s, 1H), 5.29 (s, 1H), 6.50–6.70 (m, 2H), 7.12–
7.55 (m, 7H). 13C NMR (100 MHz): dZ23.69, 102.85,
106.82, 109.17, 121.47, 122.07, 122.56, 123.02, 124.96,
127.33, 132.24, 139.25. IR (KBr) n: 3425, 3059, 2917, 2814,
1721, 1602, 1577, 1512, 1477, 1460, 1439, 1425, 1315,
1260, 1207, 1169, 1075, 1039, 1024, 872, 744, 691. MS (EI

H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
8853
C13H17NO2S2 (283.39) calcd C 55.09, H 6.04, N 4.94, found
C 54.97, H 6.38, N 4.98.
analysis for C12H15NS (205.31) calcd C 70.19, H 7.36, N
6.82, found C 70.28, H 7.30, N 6.68.
4.6.2. [2-(5,6-Dihydro-4H-thiopyran-2-yl)-4-methyl-
phenyl]methylamine (33). White solid. Mp 63–65 8C. H
4.5.3. 1-Isopropyl-1,3-dihydro-2,1-benzisothiazoline-3-
spiro-20-tetrahydrothiopyran 2,2-dioxide (29). White
solid. Mp 108–109 8C. H NMR (400 MHz): dZ1.53 (d,
1
1
NMR (400 MHz): dZ2.02–2.09 (m, 2H), 2.23 (s, 3H),
2.29–2.34 (m, 2H), 2.83 (s, 1H), 2.97–3.02 (m, 2H), 4.30 (br
s, 1H), 5.73 (t, JZ4.4 Hz, 2H), 6.53 (d, JZ8.2 Hz, 1H),
6.92 (d, JZ2.2 Hz, 1H), 7.01 (dd, JZ8.2, 2.2 Hz, 1H). 13C
NMR (100 MHz): dZ20.20, 21.76, 24.52, 27.76, 31.07,
110.19, 121.30, 125.62, 126.17, 129.61, 130.39, 130.48,
144.35. IR (KBr) n: 3412, 2908, 1632, 1612, 1579, 1515,
1473, 1443, 1431, 1401, 1313, 1276, 1265, 1168, 1128,
1070, 973, 848, 800. MS (EI 70 eV, m/z, %): 219 (MC, 81),
204 (11), 190 (49), 176 (13), 158 (42), 144 (100), 130 (12),
115 (12). HRMS for C13H17NS calcd 219.1082, found
219.1091. Elemental analysis for C13H17NS (219.33) calcd
C 71.18, H 7.81, N 6.39, found C 71.04, H 7.92, N 6.36.
JZ7.0 Hz, 3H), 1.59 (d, JZ6.9 Hz, 3H), 1.75–2.20 (m, 4H),
2.36 (ddd, JZ14.1, 13.2, 3,6 Hz, 1H), 2.50 (ddd, JZ13.7,
3.3, 3.0 Hz, 1H), 2.68 (ddd, JZ14.1, 3.5, 3.2 Hz, 1H), 3.53
(ddd, JZ13.4, 12.8, 2.8 Hz, 1H), 4.36 (dq, JZ7.0, 6.9 Hz,
1H), 6.89 (br d, JZ8.1 Hz, 1H), 7.02 (ddd, JZ7.7, 7.6,
1.0 Hz, 1H), 7.25–7.31 (m, 2H). 13C NMR (100 MHz): dZ
19.51, 21.52, 22.85, 25.36, 28.17, 31.46, 47.78, 67.35,
112.01, 122.02, 124.76, 126.56, 129.77, 138.28. IR (KBr) n:
2979, 2935, 1600, 1476, 1311, 1262, 1166, 1142, 1017, 887,
762, 749. MS (EI 70 eV, m/z, %): 297 (MC, 5), 233 (79),
218 (71), 204 (22), 190 (100), 184 (11), 162 (66), 158 (38),
157 (25), 156 (26), 148 (22), 144 (37), 130 (31, 115 (17).
HRMS for C14H19NO2S2 calcd 297.0857, found 297.0852.
Elemental analysis for C14H19NO2S2 (297.43) calcd C
56.53, H 6.44, N 4.71, found C 56.23, H 6.40, N 4.56.
4.6.3. [2-(5,6-Dihydro-4H-thiopyran-2-yl)phenyl]iso-
1
propylamine (34). Oil. H NMR (400 MHz): dZ1.23 (d,
JZ6.3 Hz, 6H), 2.02–2.09 (m, 2H), 2.32–2.37 (m, 2H),
2.99–3.00 (m, 2H), 3.64 (sept, JZ6.3 Hz, 1H), 4.50 (br s,
1H), 5.74 (dd, JZ4.4, 4.3 Hz, 1H), 6.60–6.74 (m, 2H),
7.05–7.20 (m, 2H). 13C NMR (100 MHz): dZ21.44, 21.82,
22.79, 24.56, 27.72, 111.95, 116.43, 121.71, 128.32, 129.01,
130.13, 130.45, 144.44. IR (KBr) n: 3398, 2963, 2932, 1598,
1579, 1508, 1462, 1453, 1382, 1364, 1317, 1266, 1176,
1124, 1048, 974, 875, 745. MS (EI 70 eV, m/z, %): 233
(MC, 91), 218 (67), 200 (11), 190 (100), 184 (16), 170 (11),
162 (57), 158 (50), 157 (38), 156 (35), 144 (52), 130 (39),
115 (22), 87 (80). HRMS for C14H19NS calcd 233.1238,
found 233.1232. Elemental analysis for C14H19NS (233.37)
calcd C 72.05, H 8.21, N 6.00, found C 72.01, H 8.28, N
5.80.
4.5.4. 1-Methyl-1,3-dihydroisothiazolo[4,3-b]pyridine-3-
spiro-20-tetrahydrothiopyran 2,2-dioxide (30). White
solid. Mp 108–109 8C. 1H NMR (200 MHz): dZ1.80–
1.96 (m, 2H), 2.05–2.21 (m, 2H), 2.60–2.78 (m, 3H), 3.21
(s, 3H), 3.54 (ddd, JZ15.4, 12.7, 2.8 Hz, 1H), 7.03 (dd, JZ
8.1, 1.3 Hz, 1H), 7.27 (dd, JZ8.1, 5.0 Hz, 1H), 8.26 (dd,
JZ5.0, 1.3 Hz, 1H). 13C NMR (100 MHz): dZ22.36,
25.05, 27.20, 27.75, 29.30, 68.49, 116.73, 124.72, 136.56,
143.21, 144.81. IR (KBr) n: 2933, 1585, 1575, 1472, 1437,
1312, 1244, 1230, 1200, 1175, 1159, 1131, 1032, 839, 798.
MS (EI 70 eV, m/z, %): 270 (MC, 6), 206 (89), 205 (18),191
(37), 177 (57), 173 (54), 163 (30), 159 (60), 146 (40), 145
(100), 131 (36), 119 (21). HRMS for C11H14N2O2S2 calcd
270.0497, found 270.0485. Elemental analysis for
C11H14N2O2S2 (270.38) calcd C 48.86, H 5.22, N 10.36,
found C 48.96, H 5.47, N 10.19.
4.6.4. [2-(5,6-Dihydro-4H-thiopyran-2-yl)pyridin-3-yl]
methylamine (35). Yellow needles. Mp 134–135 8C. H
1
NMR (200 MHz): dZ2.06–2.14 (m, 2H), 2.34–2.40
(m, 2H), 2.84 (s, 3H), 3.02–3.07 (m, 2H), 4.63 (br s, 1H),
6.01 (t, JZ4.4 Hz, 1H), 6.90 (dd, JZ8.2, 1.3 Hz, 1H), 7.11
(dd, JZ8.2, 4.7 Hz, 1H), 7.95 (dd, JZ4.7, 1.3 Hz, 1H). 13C
NMR (50 MHz): dZ21.64, 24.32, 27.41, 30.21, 116.87,
122.96, 123.66, 130.21, 136.63, 142.79, 143.34. IR (KBr) n:
3355, 2919, 2811, 1579, 1494, 1424, 1317, 1258, 1162, 969,
795, 755. MS (EI 70 eV, m/z, %): 206 (MC, 77), 191 (23),
177 (39), 173 (46), 163 (28), 159 (57), 146 (9100), 131 (37),
119 (21). HRMS for C11H14N2S calcd 206.0878, found
207.0886. Elemental analysis for C11H14N2S (206.30) calcd
C 64.04, H 6.84, N 13.58, found C 63.84, H 7.08, N 13.39.
4.6. Synthesis of 2-aryl-5,6-dihydro-4H-thiopyrans
32–35. General procedure
Spiro compound 27–30 (1 mmol) was heated at reflux in 1,
2-dichlorobenzene (3 mL) for 30–60 min (TLC control).
The reaction mixture was then subjected to column
chromatography. The dichlorobenzene was eluted with
hexane/ethyl acetate (50:1) and then product with hexane/
ethyl acetate 2:1. The following compounds were obtained:
4.6.1. [2-(5,6-Dihydro-4H-thiopyran-2-yl)phenyl]methyl-
1
amine (32). Oil. H NMR (400 MHz): dZ2.02–2.09 (m,
4.6.5. [2-(4,5-Dihydrothiophen-2-yl)pyridin-3-yl]methyl-
amine (37). Pyridosultam 1d (200 mg, 1 mmol) 3-chloro-
propyl thiocyanate (145 mg, 1.1 mmol), tetrabutyl-
ammonium bromide (32 mg, 0.1 mmol) in toluene (5 mL)
were stirred vigorously with 50% aqueous NaOH (10 mL) at
room temperature under argon. After 1 h the reaction
mixture was poured into water (50 mL) and the product was
extracted with dichloromethane (3!25 mL). The combined
extracts were washed with water and dried over Na2SO4.
After evaporation of solvent the product was purified by
column chromatography (hexane/ethyl acetate 2:1) and
crystallized from ethanol. Yield 106 mg (55%). Orange
2H), 2.28–2.32 (m, 2H), 2.84 (s, 3H), 2.99–3.01 (m, 2H),
4.50 (br s, 1H), 5.74 (t, JZ4.4 Hz, 1H), 6.60 (dd, JZ8.1,
1.0 Hz, 1H), 6.66 (dt, JZ7.4, 1.0 Hz, 1H), 7.08 (dd, JZ7.4,
1.6 Hz, 1H), 7.20 (ddd, JZ8.1, 7.5, 1.6 Hz, 1H). 13C NMR
(100 MHz): dZ21.71, 24.50, 27.71, 30.69, 109.82, 116.38,
121.41, 126.03, 129.14, 129.75, 130.40, 146.52. IR (KBr) n:
3419, 2918, 2833, 2813, 1598, 1579, 1514, 1460, 1427,
1316, 1267, 1168, 1070, 973, 960, 871, 853, 747. MS (EI
70 eV, m/z, %): 205 (MC, 62), 190 (7), 176 (50), 162 (13),
144 (41), 130 (100), 117 (18), 103 (5), 91 (7). HRMS for
C12H15NS calcd 205.0925, found 205.0929. Elemental

8854
H. Modrzejewska, K. Wojciechowski / Tetrahedron 61 (2005) 8848–8854
solid. Mp 119–120 8C. 1H NMR (400 MHz): dZ2.86
(d, JZ5.0 Hz, 3H), 3.01–3.07 (m, 2H), 3.31–3.36 (m,
2H), 4.56 (br s, 1H), 6.07 (t, JZ3.0 Hz, 1H), 6.92 (dd, JZ
8.3, 1.3 Hz, 1H), 7.09 (dd, JZ8.3, 4.7 Hz, 1H), 7.97 (dd,
JZ4.7, 1.3 Hz, 1H). 13C NMR (100 MHz): dZ30.32,
31.94, 37.09, 116.72, 121.92, 123.45, 137.18, 138.82,
141.34, 143.07. IR (KBr) n: 3319, 2924, 2886, 2860,
2811, 1580, 1496, 1451, 1422, 1406, 1316, 1263, 1225,
1161, 1124, 1017, 946, 793, 753. MS (EI 70 eV, m/z, %):
192 (100, MC), 177 (16), 175 (8), 164 (57), 159 (18), 149
(28), 145 (54), 133 (53), 132 (78), 131 (44), 118 (15), 104
(7). Elemental analysis for C10H12N2S (192.28) calcd C
62.47, H 6.29, N 14.57, found C 62.26, H 6.03, N 14.44.
5. Letulle, M.; Guenot, P.; Ripoll, J.-L. Tetrahedron Lett. 1991,
32, 2013–2016.
6. Danikiewicz, W.; Wojciechowski, K.; Olejnik, M.
Tetrahedron Lett. 1995, 36, 1099–1102.
7. Wojciechowski, K.; Siedlecka, U.; Modrzejewska, H.;
´
Kosinski, S. Tetrahedron 2002, 58, 7583–7588.
8. Mikołajczyk, M.; Midura, W. H.; Wladislaw, B.; Biaggio,
F. C.; Marzorati, L.; Wieczorek, M. W.; BŁaszczyk, J.
Tetrahedron 1997, 53, 2959–2972.
9. Wladislaw, B.; Marzorati, L.; Biaggio, F. C. J. Org. Chem.
1993, 58, 6132–6134.
10. Wladislaw, B.; Bueno, M. A.; Marzorati, L.; Vitta, C. D.;
Zukerman-Schpecto, J. J. Org. Chem. 2004, 69, 9296–9298.
11. Wladislaw, B.; Marzorati, L.; Uchoa, R. B.; Viertel, H.
Synthesis 1985, 553–555.
´
12. Ma˛kosza, M.; Fedorynski, M. Synthesis 1974, 274–276.
13. Wladislaw, B.; Marzorati, L.; Uchoa, R. B. Synthesis 1986,
964–965.
References and notes
´
14. Kosinski, S.; Wojciechowski, K. Eur. J. Org. Chem. 2000,
1263–1270.
1. For a review see: Wojciechowski, K. Heterocycles 2002, 57,
1717–1740.
15. Bunnett, J. F.; Kato, T.; Flynn, R. R.; Skorcz, J. A. J. Org.
Chem. 1963, 28, 1–6.
2. For a review see: Wojciechowski, K. Eur. J. Org. Chem. 2001,
3587–3605.
16. Skorcz, J. A.; Suh, J. T. J. Heterocycl. Chem. 1972, 9,
219–222.
3. Wojciechowski, K. Tetrahedron 1993, 49, 7277–7286.
4. Wojciechowski, K. Tetrahedron 1993, 49, 10017–10026.