Selective synthesis of 1,2-benzisothiazol-3-one-1-oxide nitro derivatives

Article abstract of DOI:10.1055/s-2001-16764

A new selective synthesis of 1,2-benzisothiazol-3-one-1-oxide nitro derivatives by reaction of 2-benzylthio-4-nitro- and 2-benzylthio-4,6-dinitrobenzamides with gaseous chlorine in wet CH₂Cl₂ has been developed Reactions of N-unsubstituted 2-benzylthio-4-nitro- and 2-benzylthio-4,6-dinitrobenzamides with gaseous chlorine in 60% AcOH give, instead of the S-oxides, the appropriate 1,2-benzisothiazol-3-one-1,1-dioxide nitro derivatives.

Full text of DOI:10.1055/s-2001-16764

PAPER
1659
Selective Synthesis of 1,2-Benzisothiazol-3-one-1-Oxide Nitro Derivatives
S
ynthesis of 1,2
v
-Benzisothia
g
zol-3-one-1-
e
oxide
N
itro
n
Derivativesy A. Serebryakov, Pavel G. Kislitsin, Victor V. Semenov, Sergey G. Zlotin*
N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospekt, 47, 119991, Moscow, Russia
Fax +7(095)1355328; E-mail: zlotin@cacr.ioc.ac.ru
Received 21 March 2001; revised 25 April 2001
It is known that sulfoxides can be selectively synthesized
by reaction of thioethers with halogenating agents (Cl2,8a,b
Br2,8a,c NCS,8d NBS8e) in the presence of water. The
reactions probably pass through intermediate formation
Abstract: A new selective synthesis of 1,2-benzisothiazol-3-one-1-
oxide nitro derivatives by reaction of 2-benzylthio-4-nitro- and
2-benzylthio-4,6-dinitrobenzamides with gaseous chlorine in wet
CH2Cl2 has been developed. Reactions of N-unsubstituted 2-ben-
zylthio-4-nitro- and 2-benzylthio-4,6-dinitrobenzamides with gas- of S-halogen8a or (if NBS is used as a halogenating agent)
S-succinimido8d sulfonium salts followed by hydrolysis of
eous chlorine in 60% AcOH give, instead of the S-oxides, the
appropriate 1,2-benzisothiazol-3-one-1,1-dioxide nitro derivatives.
the salts to sulfoxides with water. Advantages of this
Key words: polynitrobenzamides, chlorine, 1,2-benzisothiazole-3-
one-1-oxides, 1,2-benzisothiazole-3-one-1,1-dioxides
method are experimental simplicity and the complete ab-
sence of “over oxidation” products – sulfones. However,
this method has not been used for synthesis of N-substitut-
ed 1,2-benzisothiazol-3-one-1-oxides up to now.
1,2-Benzisothiazole-3-one-1,1-dioxides (saccharine de-
rivatives) are widely investigated in recent years as
bactericides1,2 and compounds influencing metabolism in
living organisms.3,4 1,2-Benzisothiazole-3-one-1-oxides,
including those patented as enzyme inhibitors,5 are much
less studied. The general synthesis of such compounds is
through oxidation of 1,2-benzisothiazole-3-ones. “Over
oxidation” can be prevented by using an equimolar quan-
tity of m-CPBA as an oxidant6 or, in the case of other ox-
idants such as H2O2, by careful controlling of the
oxidation temperature.7a
Herein we report for the first time on selective synthesis
of 1,2-benzisothiazole-3-one-1-oxides by reaction of the
available 2-(benzylthio) benzamide 37b,9 and 1,2-ben-
zisothiazole-3-one 47a nitro derivatives with Cl2/H2O sys-
tem.
Compounds 3b,e,j and 4b,e,j were synthesized by known
methods.7a,b,9 The 2-(benzylthio)benzamides 3c,d,f,i,k,l
were obtained by reaction of nitrobenzamides 2c,d,f,i,k,l
with benzylthiolate ion (Scheme 1, Table 1). According
to 1H NMR data they were contaminated with 5–10% of
Scheme 1
Synthesis 2001, No. 11, 28 08 2001. Article Identifier:
1437-210X,E;2001,0,11,1659,1664,ftx,en;Z03401SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

1660
E. A. Serebryakov et al.
PAPER
the appropriate 4-(benzylthio) derivatives. The minor iso- The reaction probably includes cleavage of the S–C bond
mers can be completely removed by crystallization of the in compounds 3 by the action of chlorine,11 intramolecular
crude reaction products from i-PrOH.
cyclization of sulfenyl chlorides 6 into isothiazolones 4,7a
and reversible formation of chlorosulfonium salts 78a fol-
lowed by their hydrolysis to S-oxides 5 with water8b
(Scheme 2). In anhydrous conditions the equilibrium 4D7
is apparently shifted towards the isothiazolones 4. Forma-
tion of the isothiazolones 4 was proved by isolation of the
compounds 4a,c,d,f from reactions of the appropriate sul-
fides 3a,c,d,f with gaseous Cl2 in anhydrous CH2Cl2. Ad-
dition of water to chlorine saturated solutions of the
isothiazolones 4a,c,d,f in anhydrous CH2Cl2 presumably
shifted the equilibrium 4D7 towards the salts 7 due to
their hydrolysis to S-oxides 5a,c,d,f. Unlike the gaseous
Cl2, excess of sulfuryl chloride reacted with sulfides 3 in
CH2Cl2 to afford solutions of isothiazolones 4 that did not
convert to S-oxides 5 upon addition of water to the reac-
tion mixture. The probable explanation is rapid hydrolysis
of SO2Cl2 in the presence of water or its inability to chlo-
rinate S-atom of the isothiazolone ring.
1,2-Benzisothiazol-3-one 4g, that was not formed in the
reaction of the sulfide 3g with SO2Cl2, was synthesized by
oxidation of the sulfide 3g into sulfoxide 3g’ with H2O2
followed by Pummerer-type cyclization of the sulfoxide
3g’ into isothiazolone 4g by the action of trifluoroacetic
anhydride. This method was used earlier for the synthesis
of isothiazolones fused with aromatic10a and
heteroaromatic10b rings.
We have investigated reactions of the isothiazolones 4e,g
with halogenating agents (Cl2, Br2, NBS, DBI) in the pres-
ence of water and with 1 equivalent of m-CPBA. The re-
actions were carried out in CH2Cl2 at 20 °C. It was found
that the compounds 4e,g remained unchanged under the
action of Br2, but gave the appropriate S-oxides 5e,g with
other oxidants (Scheme 1, Method A, Table 2). Use of
chlorine was preferable: the reaction proceeded much
faster, the reaction mixture was not contaminated with
byproducts (succinimide, cyanuric acid, or m-chloroben-
zoic acid) and isolation of the pure compounds 5e,g was
achieved in 66% and 79% yields by simple crystallization
of the residue remaining after evaporation of the solvent.
According to TLC, S,S-dioxides were not presented in the
reaction solutions. S-Oxides 5f,j were synthesized from
the appropriate isothiazolones 4f,j in 74% and 76% yields,
respectively by reaction with Cl2/H2O under the same
conditions (Table 2, Method A).
Sulfonyl chlorides 8, that usually form in reactions of
sulfenyl chlorides with chlorine in water solutions,12a-c
and products of their cyclization 9 were not found in the
reaction mixtures. This fact can probably be explained by
lower rate of hydrolysis of the intermediates 6 in CH2Cl2
compared to the rate of their cyclization to isothiazolones
4. The ratio of rates is changed when the reaction is car-
ried out in AcOH that forms homogenous solutions with
H2O. Chlorination of the sulfide 3a in AcOH containing
~5% of H2O gave according to 1H NMR spectra a mixture
of S-oxide 5a and S,S-dioxide 9a (product of intramolec-
ular cyclization of sulfonyl chloride 8a) in a ratio of 1.4:1.
Chlorination of the sulfide 3b under the same conditions
afforded a mixture of 5b and 9b in a ratio of 1:2. Only
“nitrosaccharines” 9a,b were isolated in 45% and 48%
yields when the chlorination reactions were carried out in
60% AcOH (Table 2).
With regards to the formation of isothiazolones 4b,e,j in
reactions of sulfides 3b,e,j with SO2Cl2 (which often acts
similar to Cl2),7a we assumed that sulfides 3 would proba-
bly react with the system Cl2/H2O to afford S-oxides 5 “in
one-pot” without isolation of the intermediate isothiazolo-
nes 4. Indeed, chlorination of the compounds 3a–l with
gaseous chlorine in CH2Cl2 containing ~5% of water,
gave the appropriate isothiazolone S-oxides 5a–l in 56–
81% yields (Scheme 1, Table 2, Method B).
As a result, a new selective synthesis of 1,2-benzisothiaz-
ole-3-one-1-oxides nitro derivatives by the reaction of
2-benzylthio-4-nitro- and 2-benzylthio-4,6-dinitrobenza-
Scheme 2
Synthesis 2001, No. 11, 1659–1664 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,2-Benzisothiazol-3-one-1-oxide Nitro Derivatives
1661
Table 1 Compounds 2–4 Prepared
Producta Yield (%) Mp (°C)
Rf (CCl4–
1H NMR (DMSO-d6)
acetone, 4:1) , J (Hz)
2c
2d
2f
75
63
61
212–214
214–217
205–208
0.05
0.16
0.18
3.32 (s, 3 H, CH3), 7.88 (d, J = 7.0, 1 H), 8.54 (d, J = 7.0, 1 Harom), 8.80 (s, 1 Harom),
8.89 (br s, 1 H, NH)
4.50 (d, J = 6.5, 2 H, CH2), 7.25–7.41 (m, 5 H, C6H5), 7.89 (d, J = 8.5, 1 Harom), 8.65
(d, J = 8.5, 1 Harom), 8.75 (s, 1 Harom), 9.42 (br s, 1 H, NH)
3.71 (s, 3 H, OCH3), 4.08 (d, J = 6.5, 2 H, CH2), 7.89 (d, J = 7.5, 1 Harom), 8.62 (d, J
= 7.5, 1 Harom), 8.77 (s, 1 Harom), 9.41 (t, J = 7.5, 1 H, NH)
2g
2h
66
50
248–249
201–204
0.08
0.16
3.69 (3, 3 H, OCH3), 4.11 (d, J = 7.0, 2 H, CH2), 9.11 (s, 2 Harom), 9.52 (br s, 1 H, NH)
4.83 (d, J = 4.5, 2 H, CH2), 7.56 (t, J = 7.5, 2 Harom), 7.68 (t, J = 7.5, 1 Harom), 7.97 (d,
J = 7.5, 1 H, HAr), 8.04 (d, J = 7.5, 2 Harom), 8.64 (d, J = 7.5, 1 Harom), 8.78 ( s, 1 Harom),
9.28 (br s, 1 H, NH)
2i
42
61
76
67
75
59
232–234
243–245
197–201
140–146
229–231
111–113
0.20
0.13
0.43
0.10
0.30
0.37
7.52 ( d, J = 7.5, 2 Harom), 7.63 (d, J = 7.5, 2 Harom), 8.07 ( d, J = 7.5, 1 Harom), 8.67 (d,
J = 7.5, 1 Harom), 8.83 (s, 1 Harom), 10.89 (s, 1 H, NH)
2k
2l
2.31 (s, 3 H, CH3), 7.15 (d, J = 7.0, 2 Harom), 7.52 (d, J = 7.0, 2 Harom), 8.02 (d, J = 6.5,
1 Harom), 8.66 (d, J = 6.5, 1 Harom), 8.81 (s, 1 Harom), 10.61 (s, 1 H, NH)
2.32 (s, 3 H, CH3), 7.18 (d, J = 6.5, 2 Harom), 7.42 (d, J = 6.5, 2 Harom), 9.16 (s, 1 Harom),
10.88 (s, 1 H, NH)
3c
3d
3f
2.76 (s, 3 H, CH3), 4.33 (s, 2 H, CH2), 7.21–7.52 (m, 5 H, C6H5), 7.61 (d, J = 8.0, 1
Harom), 8.03 (d, J = 8.0, 1 Harom), 8.12 (s, 1 Harom), 8.48 (br s, 1 H, NH)
4.34 (s, 2 H, CH2), 4.48 (d, J = 4.0, 2 H, CH2), 7.21–7.42 (m, 10 H, 2 C6H5), 7.64 (d,
J = 7.5, 1 Harom), 8.06 (d, J = 7.5, 1 Harom), 8.17 (s, 1 Harom), 8.48 (br s, 1H, NH)
3.66 (s, 3 H, OCH3), 3.98 (d, J = 6.5, 2 H, CH2), 4.30 (s, 2 H, CH2), 7.17–7.48 (m, 5
H, C6H5), 7.66 (d, J = 8.0, 1 Harom), 8.03 (d, J = 8.0, 1 Harom), 8.13 (s, 1 Harom), 9.01
(br s, 1 H, NH)
3g
3h
77
70
158–160
135–140
0.20
0.49
3.63 (s, 3 H, OCH3), 4.09 (d, J = 7.0, 2 H, CH2), 4.49 (s, 2 H, CH2), 7.20–7.54 (m, 5
H, C6H5), 8.41 (s, 1 Harom), 8.59 (s, 1 Harom), 9.30 (br s, 1 H, NH)
4.32 (s, 2 H, CH2), 4.78 (d, J = 6.5, 2 H, CH2), 7.21–7.39 (m, 6 H, C6H5 and 1 Harom),
7.42 (d, J = 7.5, 2 Harom), 7.56 (t, J = 7.5, 2 Harom), 7.66 (d, J = 7.5, 1 Harom), 7.75 (d,
J = 7.5, 1 Harom), 8.04 (s, 1 Harom), 8.06 (d, J = 8.0, 1 H, NH)
3i
73
61
68
149–158
179–182
153–156
0.50
0.60
0.66
4.33 (s, 2 H, CH2), 7.20–7.35 (m, 4 Harom), 7.38 (d, J = 8.0, 2 Harom), 7.48 (d, J = 8.0,
2 Harom), 7.68 (d, J = 7.5, 1 Harom), 7.70 (d, J = 7.5, 1 Harom), 8.08 (d, J = 7.5, 1 Harom),
8.19 (s, 1 Harom), 10.56 (br s, 1 H, NH)
3k
3l
2.31 (s, 3 H, CH3), 4.35 (s, 2 H, CH2), 7.11 (d, J = 6.5 , 2 Harom), 7.22–7.43 (m, 5 H,
C6H5), 7.57 (d, J = 7.0, 2 Harom), 7.65 (d, J = 7.0, 1 Harom), 8.07 (d, J = 7.0, 1 Harom),
8.19 (s, 1 Harom), 10.37 (br s, 1 H, NH)
2.32 (s, 3 H, CH3), 4.47 (s, 2 H, CH2), 7.14 (d, J = 6.5, 2 Harom), 7.22–7.39 (m, 3 Harom),
7.42 (d, J = 7.0, 2 Harom), 7.49 (d, J = 7.0, 2 Harom), 8.47 (s, 1 Harom), 8.63 (s, 1 Harom),
10.59 (s, 1 H, NH)
4a
4c
4d
62
64
84
275–280
222–225
158–161
0.29
0.31
0.37
8.06 (d, J = 9.0, 1 Harom), 8.16 (d, J = 9.0, 1 Harom), 8.94 (s, 1 Harom)
3.41 (s, 3 H, CH3), 8.05 (d, J = 3.5, 1 Harom), 8.19 (d, J = 3.5, 1 Harom), 9.00 (s, 1 Harom
)
5.08 (s, 2 H, CH2), 7.30–7.41 (m, 5 H, C6H5), 8.10 (d, J = 3.5, 1 Harom), 8.21 (d, J =
3.5, 1 Harom), 8.95 (s, 1 Harom
)
4f
88
167–170
0.37
3.70 (s, 3 H, CH3), 4.72 (s, 2 H, CH2), 8.09 (d, J = 7.5, 1 Harom), 8.20 (d, J = 7.5, 1
Harom), 9.02 (s, 1 Harom
)
4g
94
121–126
0.20
3.75 (s, 3 H, CH3), 4.76 (s, 2 H, CH2), 8.64 (s, 1 Harom), 9.29 (s, 1 Harom
)
a Satisfactory microanylyses obtained: C 0.29, H 0.15, N 0.26.
Synthesis 2001, No. 11, 1659–1664 ISSN 0039-7881 © Thieme Stuttgart · New York

1662
E. A. Serebryakov et al.
Table 2 Compounds 5, 9 Prepared
Prod- Yield (%) Yield (%) Mp (°C)
PAPER
filtered off, washed with H2O (2 2 mL), dried in the air, and re-
crystallized from a mixture of i-PrOH–acetone to afford 2,4 dini-
trobenzamides 2c,d,f,h,i,k as pale yellow crystals.
Rf (CCl4–
ucta
5a
5b
5c
Method A
Method B
acetone, 4:1)
2,4,6-Trinitrobenzamides 2g,l ; General Procedure
To a stirred solution of 2,4,6-trinitrobenzoyl chloride7b (1b; 0.56 g,
2.00 mmol) in anhyd benzene (6 mL) was gradually added glycine
methyl ester hydrochloride (0.28 g, 2.20 mmol) or 4-methylaniline
(0.47g, 0.49 ml, 4.40 mmol) at 5 °C. In the case of 2g, a solution of
Na2CO3 (0.44g, 4.20 mmol) in H2O (2 mL) was added afterwards.
The mixture was stirred for 20 min. The solid precipitate was fil-
tered off, washed with H2O (2 2 mL), dried in the air, and recrys-
tallized from a mixture of i-PrOH–acetone to afford compounds
2g,l as pale yellow crystals.
–
–
–
–
70
64
63
75
60
244–247
262–263
177–180
129–131
138–143
0.13
0.26
0.21
0.21
0.30
5d
5e
66
(55b, 71,c 65d)
5f
74
62
68
164–166
173–175
0.52
0.28
2-Benzylthio-4-nitro and 2-Benzylthio-4,6-dinitrobenzamides
3c,d,f–i,k,l; General Procedure
5g
79
To a stirred solution of amide 2c,d,f–i,k,l (2.00 mmol) in DMF (3
mL) were successively added the benzyl mercaptan (0.28 g, 0.27
mL, 2.20 mmol), and Na2CO3 (0.24 g, 2.20 mmol). The mixture was
stirred for 5–6 h at r.t. until the starting material disappeared (TLC
monitoring) and quenched with 0.05 M HCl (15 mL). Precipitated
solid was filtered off, washed with H2O (2 5 mL), dried in the air,
and recrystallized from i-PrOH.
(51,b, 60,c 74d)
5h
5i
–
69
56
69
81
74
45
48
168–170
253–256
222–224
193–194
208–214
281–283
267–270
0.48
0.33
0.15
0.24
0.46
0.06
0.13
–
5j
76
–
5k
5l
2-Benzylsulfonyl-N-(methoxycarbonylmethyl)-4,6-dinitro-
benzamide (3g’)
–
To a solution of the amide 3g’ (0.81 g, 2.00 mmol) in glacial AcOH
(4 mL) was added 50% H2O2 (0.57 mL, 10.00 mmol) and the mix-
ture was stirred at 35–40 °C for 3 h. The solvent was evaporated un-
der reduced pressure. The oily residue was solidified by the addition
of H2O (5 mL), filtered, dried in the air and recrystallized from
i-PrOH.
9a
9b
–
–
a Satisfactory microanalyses obtained: C 0.31, H 0.19, N 0.22.
b Oxidant: NBS/H2O.
c Oxidant: DBI/H2O.
d Oxidant: m-CPBA.
6-Nitro- and 4,6-Dinitro-1,2-benzisothiazol-3-ones 4a,c,d,f;
General Procedures
Reaction with SO2Cl2: To a stirred suspension of 3a,c,d,f (2.0
mmol) in anhyd CH2Cl2 (6 mL) was added SO2Cl2 (0.50 g, 0.30 mL,
2.80 mmol). The mixture was stirred at 15–20 °C for 30 min and di-
luted with hexane (10 mL). Precipitated yellow solid was filtered
off, and recrystallized from a mixture of i-PrOH–acetone.
mides with gaseous chlorine in wet CH2Cl2 has been de-
veloped. It is worth to mention that the starting
benzamides are easily available from 2,4-di- and 2,4,6-
trinitrotoluenes7b,13 and the proposed method can be con-
sidered as a method for synthetic utilization of the explo-
Reaction with Cl2: A stirred suspension of 3a,c,d,f (2.00 mmol) in
anhyd CH2Cl2 (6 mL) was saturated with gaseous Cl2 for 5 min. The
sive aromatic polynitro compounds (including solvent and excess of Cl2 were evaporated under reduced pressure
trinitrotoluene see also Ref.14a–c).
and the solid residue was recrystallized from a mixture of i-PrOH–
acetone.
2,4-Di- and 2,4,6-trinitrobenzoic acids were prepared by known
methods7b,11 and 2,4,6-trinitrobenzoyl chloride 1b according to the
literature.7b Following compounds were synthesized by reported
methods: compounds 2a and 3a,9 compounds 2b,e,j and 3b,e,j,7b
and 4b,e,j.7a
2-Methoxycarbonylmethyl-4,6-dinitro-1,2-benzisothiazole-3-
one (4g)
To a stirred solution of the amide 3g’ (0.84 g, 2.00 mmol) in anhyd
CH2Cl2 (10 mL) was slowly added (CF3CO)2O (0.46 g, 0.31 mL,
2.20 mmol) at 5 °C. The mixture was stirred for 1 h at the same tem-
perature and poured into a solution of NaHCO3 (0.37 g, 4.40 mmol)
in H2O (5 mL). Organic layer was separated and the aqueous solu-
tion was extracted with CHCl3 (5 mL). The combined organic layers
were dried (MgSO4), the solvent was evaporated and the solid resi-
due was recrystallized from i-PrOH.
2,4-Dinitrobenzamides 2c,d,f,h,i,k; General Procedure
To a suspension of 2,4-dinitrobenzoic acids (0.42 g, 1.98 mmol) in
anhyd benzene (5 mL) were added SOCl2 (0.72 g, 0.44 mL, 6.00
mmol) and DMF (1 drop) successively. The mixture was refluxed
for 3 h, benzene and the excess of SOCl2 were evaporated under re-
duced pressure. Benzene (3 mL) was added to the oily residue and
the solvent was evaporated again to remove the traces of SOCl2. The
residue was dissolved in benzene (3 mL) and to this solution of 2,4-
dinitrobenzoyl chloride 1c,d,f,h,i,k was added gradually the appro-
priate amine (4.20 mmol) at 5 °C under vigorous stirring [in the case
of 2c 25% aq solution of MeNH2 was used, in the case of 2f and 2h
glycine methyl ester hydrochloride and 2-aminoacetophenone hy-
drochloride, respectively, were added first and a solution of Na2CO3
(0.44 g, 4.20 mmol) in H2O (2 mL) afterwards]. The precipitate was
6-Nitro- and 4,6-Ninitro-1,2-benzisothiazol-3-one-1-oxides
5a–l; General Procedure
Method A: A solution of 4e,f,g,j (2.00 mmol) in a mixture of
CH2Cl2 (10 mL) and H2O (0.50 ml) was saturated with gaseous Cl2
for 5 min. The mixture was stirred for 10 min at r.t., the solvent and
excess of Cl2 were removed in vacuo, and the solid residue was re-
crystallized from i-PrOH.
Method B: A suspension of amide 3a–l (2.00 mmol) in a mixture of
CH2Cl2 (10 mL) and H2O (0.50 mL) was saturated with gaseous Cl2
Synthesis 2001, No. 11, 1659–1664 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of 1,2-Benzisothiazol-3-one-1-oxide Nitro Derivatives
1663
Table 3 Spectroscopic Data for Compounds 5, 6
Product
1H NMR (DMSO-d6)
, J (Hz)
EI-MS
m/z (%)
5a
8.13 (d, J = 7.0, 1 Harom), 8.64 (d, J = 7.5, 1 Harom), 9.04 (s, 1
Harom), 11.79 (br s, 1 H, NH)
212 (48), 196 (4), 182 (2), 166 (73), 136 (5), 120 (19), 103
(77), 75 (100)
5b
5c
9.13 (s, 1 Harom), 9.35 (s, 1 Harom
)
257 (10), 211 (13), 194 (38), 148 (18), 74 (100)
3.33 (s, 3 H, CH3), 8.17 (d, J = 7.5, 1 Harom), 8.62 (d, J = 7.5, 1 226 (45), 197 (14), 166 (100), 120 (9)
Harom), 9.09 (s, 1 Harom
)
5d
4.88 (d, J = 14.5, 1 H, CH2), 5.20 (d, J = 14.5, 1 H, CH2), 7.25– 302 (22), 274 (2), 197 (100), 120 (9)
7.49 (m, 5 H, C6H5), 8.20 (d, J = 9.5, 1 Harom), 8.62 (d, J = 9.5, 1
Harom), 9.12 (s, 1 Harom
)
5e
5f
4.85 (d, J = 14.5, 1 H, CH2), 5.15 (d, J = 14.5, 1 H, CH2), 7.23– 347 (11), 178 (14), 148 (15), 120 (14), 105 (100), 91 (94), 77
7.86 (m, 5 H, C6H5), 9.09 (s, 1 Harom), 9.36 (s, 1 Harom (24), 65 (29)
)
3.71 (s, 3 H, OCH3), 4,70 (d, J = 9.5, 1 H, CH2), 4.88 (d, J = 9.5, 284 (34), 225 (60), 197 (84), 166 (100), 151 (34), 75 (52)
1 H, CH2), 8.21 (d, J = 8.5, 1 Harom), 8.65 (d, J = 8.5, 1 Harom),
9.11 (s, 1 Harom
)
5g
5h
3.73 (s, 3H, OCH3), 4.56 (d, J = 12.5, 1 H, CH2), 4.80 (d, J =
329 (15), 270 (90), 254 (28), 194 (100), 148 (33)
12.5, 1 H, CH2), 9.16 (s, 1 Harom), 9.42 (s, 1 Harom
)
5,43 (d, J = 12.0, 1 H, CH2), 5.61 (d, J = 12.0, 1 H, CH2), 7.59 330 (2), 284 (11), 256 (5), 197 (100), 148 (33)
(t, J = 7.5, 2 Harom), 7.72 (t, J = 7.5, 1 Harom), 8.08 (d, J = 7.5, 2
Harom), 8.25 (d, J = 7.5, 1 Harom), 8.69 (d, J = 7.5, 1 Harom), 9.16
(s, 1 Harom
)
5i
7.49 (d, J = 7.5, 2 Harom), 7.77 (d, J = 7.5, 2 Harom), 8.27 (d, J = 366 (64), 350 (29), 302 (49), 256 (42), 75 (100)
7.5, 1 Harom), 8.69 (d, J = 7.5, 1 Harom), 9.18 (s, 1 Harom
)
5j
7.49 (d, J = 7.5, 2 Harom), 7.77 (d, J = 7.5, 2 Harom), 9.19 (s, 1
Harom), 9.45 (s, 1 Harom),
412 (13), 395 (3), 381 (3), 332 (5), 268 (37), 90 (100)
302 (21), 286 (2), 238 (61), 192 (9), 75 (100)
5k
5l
2.41 (s, 3 H, CH3), 7.33–7.42 (m, 4 Harom), 8.23 (d, J = 8.0, 1
Harom), 8.58 (d, J = 8.0, 1 Harom), 9.13 (s, 1 Harom
)
2.41 (s, 3 H, CH3), 7.36–7.42 (m, 4 Harom), 9.16 (s, 1 Harom), 9.42 347 (100), 317 (7), 253 (34), 225 (19), 179 (54)
(s, 1 Harom
)
9a
9b
8.11 (d, J = 7.5, 1 Harom), 8.34 (d, J = 7.5, 1 Harom), 8.56 (s, 1
229 (28), 165 (58), 149 (51), 103 (61), 75 (100)
273 (20), 209 (28), 74 (100)
Harom
)
8.70 (s, 1 Harom), 8.92 (s, 1 Harom
)
for 5 min, and stirred for 10 min at r.t. Workup procedure is the
same as described in Method A.
6-Nitro- and 4,6-Dinitro-1,2-benzisothiazol-3-one-1,1-dioxides
9a,b; General Procedure
A solution of the amide 3a,b (2.00 mmol) in 60% AcOH (6 mL) was
saturated with gaseous Cl2 for 5 min. The mixture was kept at r.t for
10 min, the solvent evaporated under reduced pressure and the oily
residue was purified by recrystallization from i-PrOH.
Reaction of Isothiazolones 4e,g with N-Bromoamides in the
Presence of Water; General Procedure
To a solution of 4e,g (2.00 mmol) in a mixture of CH2Cl2 (10 mL)
and H2O (0.50 mL) was added NBS or DBI (2.40 mmol) and the
mixture was stirred at r.t. for 24 h. The precipitate formed was fil-
tered off, the organic solution was washed with H2O (3 5 mL) and
dried (MgSO4). The solvent was evaporated under reduced pres-
sure, the remaining viscous oil was washed with hexane (3 mL) and
recrystallized from i-PrOH to afford the S-oxides 5e,g.
References
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r.t. for 4 h. Workup procedure was the same as described for the re-
action with N-bromoamides.
Synthesis 2001, No. 11, 1659–1664 ISSN 0039-7881 © Thieme Stuttgart · New York

1664
E. A. Serebryakov et al.
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Synthesis 2001, No. 11, 1659–1664 ISSN 0039-7881 © Thieme Stuttgart · New York