Nitro derivatives of cyclic sulfoximides of the 1,2-benzoisothiazole series

Article abstract of DOI:10.1023/A:1020987628760

Nitro derivatives of 1-R-1,2-benzoisothiazol-3-one 1-oxide were synthesized by the reactions of 2-alkyl(phenyl)thio-4-nitro- and 4,6-dinitro-2-(phenylthio)benzamides with chlorine in 60% acetic acid. Analogous reactions of 2-(n-butylthio)-4-nitro- and 2-(tert-butylthio)-4-nitrobenzamides with chlorine afforded 2-butyl- and 2-H-1,2-benzoisothiazol-3-one 1-oxides, respectively. The proposed reaction mechanism includes the formation and subsequent transformations of S-alkyl-S-aryl- and S,S-diarylchlorosulfonium chlorides.

Full text of DOI:10.1023/A:1020987628760

Russian Chemical Bulletin, International Edition, Vol. 51, No. 8, pp. 1549—1555, August, 2002
1549
Nitro derivatives of cyclic sulfoximides
of the 1,2ꢀbenzoisothiazole series
E. A. Serebryakov and S. G. Zlotinꢀ
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences,
47 Leninsky prosp., 119991 Moscow, Russian Federation.
Fax: +7 (095) 135 5328. Eꢀmail: zlotin@cacr.ioc.ac.ru
Nitro derivatives of 1ꢀRꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxide were synthesized by the reacꢀ
tions of 2ꢀalkyl(phenyl)thioꢀ4ꢀnitroꢀ and 4,6ꢀdinitroꢀ2ꢀ(phenylthio)benzamides with chloꢀ
rine in 60% acetic acid. Analogous reactions of 2ꢀ(nꢀbutylthio)ꢀ4ꢀnitroꢀ and 2ꢀ(tertꢀbutylthio)ꢀ
4ꢀnitrobenzamides with chlorine afforded 2ꢀbutylꢀ and 2ꢀHꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone
1ꢀoxides, respectively. The proposed reaction mechanism includes the formation and subseꢀ
quent transformations of SꢀalkylꢀSꢀarylꢀ and S,Sꢀdiarylchlorosulfonium chlorides.
Key words: 1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxide, 1ꢀRꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxide,
alkanethiols, thiophenol, 2,4ꢀdinitrobenzamides, 2,4,6ꢀtrinitrobenzamides.
Scheme 1
Cyclic sulfoximides, particularly 1,2ꢀbenzoisothiazole
derivatives, possess various types of biological activity1
such as antisecretory,2 antihypertensive,3 and antiꢀ
spasmodic4 and can also reduce the sugar level in
blood.4 Such compounds are most commonly syntheꢀ
sized by reactions of orthoꢀ(alkylsulfinyl)benzoates with
HN3.1,5—7 However, this technique is inconvenient for
laboratory practice because of the risk of explosions.
Nitroꢀ1,2ꢀbenzoisothiazole sulfoximides remain unknown
so far.
Recently, we have developed a selective synthesis of
2ꢀRꢀ6ꢀnitroꢀ and 2ꢀRꢀ4,6ꢀdinitroꢀ1,2ꢀbenzoisothiazolꢀ
3ꢀone 1ꢀoxides from the corresponding nitro derivatives
of NꢀRꢀ2ꢀ(benzylthio)benzamide and chlorine in aqueꢀ
ous organic solvents.8 One could assume that analogous
reactions with 2ꢀRSꢀbenzamides containing no easily
leaving benzyl group would proceed with retention of
the C—S bond, yielding 1,2ꢀbenzoisothiazole sulfꢀ
oximides.
To verify this assumption, the oxidative chlorination
of 2ꢀRSꢀ4ꢀnitroꢀ and 2ꢀRSꢀ4,6ꢀdinitrobenzamides bearꢀ
ing Sꢀalkyl and Sꢀphenyl substituents was studied.
The starting benzamides 2a—h were prepared by reꢀ
actions of 2,4ꢀdinitroꢀ and 2,4,6ꢀtrinitrobenzamides
(1a,b) with the corresponding thiols in DMF in the presꢀ
ence of Na2CO3.9 The reactions are regioselective; the
reaction products recrystallized from PriOH are indiꢀ
vidual 2ꢀRSꢀnitrobenzamides 2a—h (1H NMR data)
(Scheme 1).
1: R = H (a), NO2 (b)
2
a
b
c
d
R
H
H
H
H
R´
2
e
f
g
h
R
H
H
NO2
NO2
R´
Et
But
Ph
Et
Prn
Bun
nꢀC8H17
Ph
and 2ꢀphenylthioꢀ4ꢀnitrobenzamides 2a,b,d,f, as well as
4,6ꢀdinitroꢀ2ꢀphenylthiobenzamide (2h), react with chloꢀ
rine in 60% AcOH without cleavage of the C—S bond to
give the corresponding 1ꢀR´ꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone
1ꢀoxides 3a,b,d,f,h in 60—74% yields as the only reacꢀ
tion products. Chlorination of 2ꢀ(nꢀbutylthio)ꢀ4ꢀnitroꢀ
benzamide (2c) under the above conditions is accompaꢀ
nied by migration of the Bun group from the sulfur atom
to the N atom, affording 2ꢀ(nꢀbutyl)ꢀ6ꢀnitroꢀ1,2ꢀbenzoꢀ
isothiazolꢀ3ꢀone 1ꢀoxide (4c) in 72% yield. The major
products of the reactions of 2ꢀ(tertꢀbutylthio)ꢀ4ꢀnitroꢀ
benzamide (2e) with chlorine in 60% AcOH and in aqueꢀ
ous CH2Cl2 (water content is ∼5%) are 6ꢀnitroꢀ1,2ꢀ
benzoisothiazolꢀ3ꢀone 1,1ꢀdioxide (5) and 6ꢀnitroꢀ1,2ꢀ
benzoisothiazolꢀ3ꢀone 1ꢀoxide (6) in 36 and 34% yields,
respectively. Finally, chlorination of 2ꢀ(ethylthio)ꢀ4,6ꢀ
dinitrobenzamide (2g) in 60% AcOH gives sulfone 7
containing no isothiazole ring (Scheme 2).
It turned out that the oxidative chlorination of comꢀ
pounds 2a—h affords structurally different products, deꢀ
pending on the nature of the substituent at the S atom and
the number of nitro groups. Thus 2ꢀalkylthioꢀ (R´ ≠ Bu)
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1426—1431, August, 2002.
1066ꢀ5285/02/5108ꢀ1549 $27.00 © 2002 Plenum Publishing Corporation

1550
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Serebryakov and Zlotin
Scheme 2
Reagents and conditions: i. Cl2, 60% AcOH; ii. Cl2, CH2Cl2—H2O (5%).
Note. Substituents R and R´ in compounds 3a,b,d,f,h and 4c correspond to those for compounds 2 in Scheme 1.
The compounds obtained were characterized by IR
and 1H NMR spectra and elemental analysis data
(Tables 1—3). The structures of sulfoximides 3a,b,d,f,h
and oxide 4c were determined by comparing their physiꢀ
cochemical and spectral data with those of 2ꢀR´ꢀ1,2ꢀbenꢀ
zoisothiazolꢀ3ꢀone 1ꢀoxides 4a,c,d,f,h (Scheme 3) synꢀ
thesized from 2ꢀ(benzylthio)benzamides 9a,c,d,f,h acꢀ
cording to the known procedure.8
benzoisothiazolꢀ3ꢀone 1ꢀoxides 3a,b,d,f,h show less
intense CO absorption bands compared to those
for 2ꢀR´ꢀ6ꢀnitroꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxides
4a,c,d,f,h; in addition, these bands appear in the range
of longer wavelengths (∼1600 versus 1645—1715 cm–1),
which is characteristic of cyclic sulfimides.1 In the
1H NMR spectra of compounds 3a,b,d, signals for the
methylene protons are shifted upfield (δ ∼3.50) relative
to analogous signals for products 4a,c,d (δ 3.70—3.95),
which is usually observed while comparing N—CH2ꢀ and
S—CH2ꢀcontaining compounds.10 Note that the N–CH2
protons in 2ꢀR´ꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxides
4a,c,d are magnetically nonequivalent, whereas those in
1ꢀR´ꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxides 3a,b,d have the
same chemical shifts, probably because of a lower barrier
to the inversion of the S atom in compounds 3a,b,d
with the ylide structure.11 The methylene protons in
1ꢀR´ꢀisomers 3 are spatially closer to the annelated aroꢀ
matic ring than those in 2ꢀR´ꢀisomers 4; this was conꢀ
firmed by the nuclear Overhauser effect for the CH2 and
H(7) protons in compound 3a, which did not occur in
compound 4a.
Scheme 3
The product of oxidative chlorination of 2ꢀ(nꢀbutylꢀ
thio)ꢀ4ꢀnitrobenzamide (2c) proved to be identical with
compound 4c obtained independently from 9c, and
isothiazolones 5 and 6 are identical to authentic samples
synthesized according to the known method.8
Apparently, the oxidative chlorination of 2ꢀR´Sꢀbenzꢀ
amides 2a—h proceeds through the formation of chloroꢀ
sulfonium chlorides 10, whose subsequent reaction pathꢀ
ways depend on the nature of substituents R and R´
(Scheme 4). For R´ = Alk (R´ ≠ Bu) and R´ = Ph,
chlorides 10 are probably hydrolyzed with water conꢀ
Reagents and conditions: i. PhCH2SH—K2CO3, DMF. ii. Cl2,
CH2Cl2—H2O (5%).
Note. Substituents R and R´ in compounds 4, 8, and 9 correꢀ
spond to those for compounds 2 in Scheme 1.
Compounds 3a,d,f,h differ from isomeric isothiazoꢀ
slones 4a,d,f,h in melting points and retention factors Rf
(Tables 2, 3). The IR spectra of 1ꢀR´ꢀ6ꢀnitroꢀ1,2ꢀ

Nitro derivatives of cyclic sulfoximides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1551
Table 1. Yields, melting points, and elemental analysis data for compounds 2a—h, 3a,b,d,f,h, 4a,c,d,f,h, 8a,c,d,f, and
9a,c,d,f
Comꢀ
pound
Yield
(%)
M.p./°C
Found
Calculated
Molecular
formula
(%)
С
Н
N
S
2a
2b
2c
2d
2e
2f
90
80
80
76
62
72
75
64
68
79
65
71
69
84
72
61
68
74
54
83
69
75
72
82
74
78
193—197
178—180
137—141
121—125
154—158
195—197
171—178
238—243
152—154
119—121
100—102
144—147
160—162
172—176
113—115
58—60
47.92
47.78
50.27
49.99
52.10
51.95
58.29
58.04
52.16
51.95
57.26
56.93
40.03
39.85
48.99
48.90
44.85
45.00
47.01
47.24
55.38
55.54
54.20
54.16
47.00
46.85
45.15
45.00
49.42
49.25
55.76
55.54
54.46
54.16
46.94
46.85
45.27
45.19
49.60
49.44
55.98
55.72
54.30
54.36
61.02
60.74
62.93
62.77
66.16
65.97
66.21
65.92
4.40
4.45
4.97
5.03
5.68
5.55
7.00
7.14
5.49
5.55
3.80
3.67
3.41
3.34
2.75
2.84
3.26
3.36
4.05
3.96
6.14
6.21
2.88
2.80
2.21
2.12
3.20
3.36
4.40
4.51
6.32
6.21
2.93
2.80
2.08
2.12
3.71
3.79
5.02
4.90
6.63
6.55
3.25
3.16
5.01
5.10
5.92
5.85
6.94
7.05
4.55
4.43
12.53
12.38
11.40
11.66
10.88
11.02
8.89
14.02
14.17
13.15
13.34
12.30
12.61
9.98
10.33
12.47
12.61
11.43
11.69
11.71
11.82
9.88
10.04
13.40
13.35
12.79
12.61
10.27
9.88
10.95
11.12
9.84
C9H10N2O3S
C10H12N2O3S
C11H14N2O3S
C15H22N2O3S
C11H14N2O3S
C13H10N2O3S
C9H9N3O5S
C13H9N3O5S
C9H8N2O4S
C10H10N2O4S
C15H20N2O4S
C13H8N2O4S
C13H7N3O6S
C9H8N2O4S
C11H12N2O4S
C15H20N2O4S
C13H8N2O4S
C13H7N3O6S
C9H9N3O5
9.02
10.79
11.02
10.10
10.21
15.21
15.49
13.13
13.16
11.39
11.66
11.26
11.02
8.82
8.64
9.60
9.72
12.75
12.61
11.83
11.66
10.28
10.44
8.63
2g
2h
3a
3b
3d
3f
3h
4a
4c
4d
4f
9.62
13.13
13.35
12.14
11.95
10.05
9.88
10.97
11.12
9.45
8.64
9.55
9.72
211—213
235—240
198—200
122—125
107—110
195—199
168—170
133—135
110—112
155—158
4h
8a
8c
8d
8f
12.77
12.61
17.39
17.57
15.61
15.72
12.84
13.00
14.83
14.63
9.10
8.85
8.00
8.13
6.75
6.99
7.47
7.69
9.62
—
—
—
—
C11H13N3O5
C15H21N3O5
C13H9N3O5
9a
9c
9d
9f
9.89
10.13
9.52
9.31
7.73
8.00
9.04
8.80
C16H16N2O3S
C18H20N2O3S
C22H28N2O3S
C20H16N2O3S

1552
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Serebryakov and Zlotin
1
Table 2. H NMR spectra of nitrobenzamides 2a—h, 8a,c,d,f, and 9a,c,d,f
Comꢀ
pound
δ (J/Hz)
2a
2b
1.31 (t, 3 H, СН2СН3, J = 5.0); 3.02 (q, 2 H, СН2СН3, J = 8.0); 7.62 (d, 1 H, Н(6), J = 6.0); 7.63,
7.96 (both s, 1 H each, NH); 8.00 (d, 1 H, Н(5), J = 6.0); 8.08 (s, 1 H, Н(3))
1.07 (t, 3 H, СН2СН2СН3, J = 2.0); 1.32 (q, 2 H, СН2СН2СН3, J = 6.5); 3.05 (q, 2 H, СН2СН2СН3, J = 8.0);
7.59 (br.s, 1 H, NH); 7.67 (d, 1 H, Н(6), J = 4.5); 7.72 (br.s, 1 H, NH); 7.94 (d, 1 H, Н(5), J = 4.5);
8.08 (s, 1 H, Н(3))
2c
2d
2e
0.88 (t, 3 H, СН2СН2СН2СН3, J = 6.0); 1.30—1.43 (m, 2 H, СН2СН2СН2СН3); 1.58—1.71 (m, 2 H, СН2СН2СН2СН3);
3.05 (t, 2 H, СН2СН2СН2СН3, J = 6.5); 7.61 (br.s, 1 H, NH); 7.62 (d, 1 H, Н(6), J = 6.0); 7.79 (br.s, 1 H, NH);
7.89 (d, 1 H, Н(5), J = 6.0); 7.92 (s, 1 H, Н(3))
0.88 (t, 3 H, (СН2)7СН3, J = 3.5); 1.31 (br.s, 8 Н, (СН2)3(СН2)4СН3); 1.46 (m, 2 H, (СН2)2СH2(СН2)4СН3);
1.68 (m, 2 H, СН2СH2CH2(СН2)4СН3); 2.98 (t, 2 H, СН2(СH2)2(СН2)4СН3, J = 7.0); 7.44 (br.s, 1 H, NH);
7.67 (d, 1 H, Н(6), J = 9.0); 7.81 (br.s, 1 H, NH); 7.97 (d, 1 H, Н(5), J = 9.0); 8.03 (s, 1 H, Н(3))
1.28 (s, 9 Н, С(СН3)3); 7.64 (d, 1 H, Н(6), J = 7.5); 7.67, 7.79 (both br.s, 1 H each, NH);
7.85 (d, 1 H, Н(5), J = 7.5); 7.92 (s, 1 H, Н(3))
2f
2g
7.58 (m, 5 H, Ph); 7.78 (d, 1 H, Н(6), J = 8.5); 7.86 (s, 1 H, Н(3)); 8.05 (d, 1 H, Н(5), J = 8.5); 8.28 (br.s, 2 H, NH2)
1.31 (t, 3 H, СН2СН3, J = 5.0); 3.19 (q, 2 H, СН2СН3, J = 5.5); 7.88, 8.06 (both s, 1 H each, NH2);
8.33 (s, 1 H, Н(5)); 8.54 (s, 1 H, Н(3))
2h
8a
7.42—7.62 (m, 5 H, Ph); 7.78 (s, 1 H, NH); 7.87 (s, 1 H, H(5)); 8.07 (s, 1 H, NH); 8.54 (s, 1 H, H(3))
1.18 (t, 3 H, СН2СН3, J = 2.0); 3.31 (quint, 2 H, СН2СН3, J = 3.5); 7.83 (d, 1 H, Н(6), J = 5.5);
8.56 (d, 1 H, Н(5), J = 5.5); 8.73 (s, 1 H, Н(3)); 8.75 (br.s, 1 H, NH)
8c
8d
0.96 (t, 3 H, СН2СН2СН2СН3, J = 8.5); 1.42 (q, 2 H, СН2СН2СН2СН3, J = 8.5);
1.56 (q, 2 H, СН2СН2СН2СН3, J = 8.5); 3.29 (q, 2 H, СН2СН2СН2СН3, J = 7.5); 7.82 (d, 1 H, Н(6), J = 7.5);
8.58 (d, 1 H, Н(5), J = 7.5); 8.60 (s, 1 H, Н(3)); 8.73 (br.s, 1 H, NH)
0.88 (t, 3 H, (СН2)7СН3, J = 3.5); 1.22—1.41 (m, 10 Н, СН2СН2(СН2)5СН3);
1.56 (q, 2 H, СН2СН2(СН2)5СН3, J = 7.5); 3.26 (q, 2 H, СН2СН2(СН2)5СН3, J = 7.5);
7.82 (d, 1 H, Н(6), J = 9.5); 8.58 (d, 1 H, Н(5), J = 9.5); 8.72 (s, 1 H, Н(3)); 8.75 (br.s, 1 H, NH)
7.11 (d, 1 H, pꢀН (Ph), J = 7.0); 7.33 (t, 2 H, mꢀН (Ph), J = 7.0); 7.62 (d, 2 H, oꢀН (Ph), J = 7.5);
8.03 (d, 1 H, Н(6), J = 9.0); 8.67 (d, 1 H, Н(5), J = 9.0); 8.82 (s, 1 H, Н(3)); 10.70 (br.s, 1 H, NH)
1.15 (t, 3 H, СН2СН3, J = 3.5); 3.28 (quint, 2 H, СН2СН3, J = 10.0); 4.29 (s, 2 H, СН2);
7.24 (d, 1 H, pꢀН (Ph), J = 2.5); 7.32 (t, 2 H, mꢀН (Ph), J = 6.5); 7.39 (d, 2 H, oꢀН (Ph), J = 5.5);
7.59 (d, 1 H, Н(6), J = 6.5); 8.00 (d, 1 H, Н(5), J = 6.5); 8.12 (s, 1 H, Н(3)); 8.42 (br.s, 1 H, NH)
0.91 (t, 3 H, СН2СН2СН2СН3, J = 7.0); 1.40 (q, 2 H, СН2СН2СН2СН3, J = 4.5);
1.56 (q, 2 H, СН2СН2СН2СН3, J = 6.5); 3.28 (q, 2 H, СН2СН2СН2СН3, J = 2.0); 4.25 (s, 2 H, СН2);
7.21 (d, 1 H, pꢀН (Ph), J = 3.5); 7.28 (t, 2 H, mꢀН (Ph), J = 7.5); 7.38 (d, 2 H, oꢀН (Ph), J = 7.5);
7.56 (d, 1 H, Н(6), J = 9.5); 7.97 (d, 1 H, Н(5), J = 9.5); 8.09 (s, 1 H, Н(3)); 8.24 (br.s, 1 H, NH)
0.62 (t, 3 H, (СН2)7СН3, J = 4.5); 1.20—1.42 (m, 10 H, СН2СН2(СН2)5СН3);
8f
9a
9c
9d
1.52 (q, 2 H, СН2СН2(СН2)5СН3, J = 6.5); 3.21 (q, 2 H, СН2СН2(СН2)5СН3, J = 6.5);
4.06 (s, 2 H, СН2); 7.25 (d, 1 H, pꢀН (Ph), J = 5.5); 7.29 (t, 2 H, mꢀН (Ph), J = 7.5);
7.39 (d, 2 H, oꢀН (Ph), J = 5.0); 7.56 (d, 1 H, Н(6), J = 5.0); 7.99 (d, 1 H, Н(5), J = 5.0);
8.12 (s, 1 H, Н(3)); 8.38 (br.s, 1 H, NH)
9f
4.32 (s, 2 H, СН2); 7.05—7.49 (m, 10 H, 2 Ph); 7.78 (d, 1 H, Н(6), J = 9.0); 8.09 (d, 1 H, Н(5), J = 9.0);
8.19 (s, 1 H, Н(3)); 10.42 (br.s, 1 H, NH)
tained in the solvent into Sꢀoxides 11. The latter are
either oxidized into sulfone 7 (R = NO2, R´ = Et) or
chlorinated at the carbamoyl N atom to give Nꢀchloroꢀ
amines 12, which undergo cyclization into sulfoximides
3a,b,d,f,h according to the known scheme.12 The formaꢀ
tion of intermediate Sꢀoxides 11 was confirmed by the
synthesis of compound 11a from amide 2a and MCPBA
followed by its conversion into sulfoximide 3a under the
action of Cl2 in 60% AcOH. Unlike Sꢀoxide 11a, sulfone
13 obtained by oxidation of amide 2a with an excess of
MCPBA does not yield sulfoximide 3a upon chlorinaꢀ
tion under these conditions.
Presumably, the direction of the reactions of Sꢀoxꢀ
ides 11 with chlorine depends on the relative nucleophiꢀ
licity of the N and S atoms. Thus for R = H, the more
nucleophilic N atom is chlorinated to give compounds
3a,b,d,f; for R = NO2 and R´ = Alk, chlorination of the
S atom yields sulfone 7.
(tertꢀButyl) chlorosulfonium chloride (10e) containꢀ
ing the easily leaving But group seems to eliminate
tertꢀbutyl chloride,13 giving products 5 and 6 according
to the known scheme.8
The available data are insufficient to explain the S→N
migration of the Bun group in the reaction of comꢀ

Nitro derivatives of cyclic sulfoximides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1553
Table 3. Retention factors (Rf), IR, and 1H NMR data for the nitro derivatives of 1ꢀR´ꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxides
3a,b,d,f,h and 2ꢀR´ꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxides 4a,c,d,f,h
Comꢀ Rf
IR, ν/cm–1
δ (J/Hz)
pound
С=О S=O (s) NO2 (s)
3a
3b
0.38 1600 w 1140
1360
1.29 (t, 3 H, СН2СН3, J = 2.0); 3.53 (q, 2 H, СН2СН3, J = 2.5);
8.44 (d, 1 H, Н(4), J = 7.5); 8.69 (d, 1 H, Н(5), J = 7.5); 8.75 (s, 1 H, Н(7))
1.08 (t, 3 H, СН2СН2СН3, J = 1.5); 1.78 (m, 2 H, СН2СН2СН3);
3.49 (t, 2 H, СН2СН2СН3, J = 6.5); 8.42 (d, 1 H, Н(4), J = 9.0);
8.71 (d, 1 H, Н(5), J = 9.0); 8.75 (s, 1 H, Н(7))
1160
0.36 1600 w 1130
1150
1540
1350
1540
3d
0.44 1600 w 1120
1155
1345
1540
0.88 (t, 3 H, (СН2)7СН3, J = 1.5); 1.27 (br.s, 8 H, (СН2)3(СН2)4СН3);
1.46 (br.s, 2 H, (СН2)2СH2(СН2)4СН3); 1.73 (br.s, 2 H, СН2СH2CH2(СН2)4СН3);
3.47 (t, 2 H, СН2(СН2)6СН3, J = 2.5); 8.42 (d, 1 H, Н(4), J = 6.0);
8.64 (d, 1 H, Н(5), J = 6.0); 8.68 (s, 1 H, Н(7))
3f
0.31 1610 w 1140
1170
0.31 1610 w 1135
1165
0.18 1645 s 1135
1155
1360
1540
1355
1540
1350
1540
7.67—7.89 (m, 3 H, pꢀН + mꢀН (Ph)); 8.11 (d, 2 H, oꢀН (Ph), J = 10.0);
8.43 (d, 1 H, Н(4), J = 8.5); 8.69 (d, 1 H, Н(5), J = 8.5); 8.91 (s, 1 H, Н(7))
7.75 (t, 2 H, mꢀН (Ph), J = 7.5); 7.93 (d, 1 H, pꢀН (Ph), J = 8.0);
8.23 (d, 2 H, oꢀН (Ph), J = 7.5); 9.21 (s, 1 H, Н(5)); 9.49 (s, 1 H, Н(7))
1.36 (t, 3 H, СН2СН3, J = 4.0); 3.83 (dt, 1 H, СН2, J1 = 6.5, J2 = 5.0);
3.93 (dt, 1 H, СН2, J1 = 6.5, J2 = 5.0); 8.18 (d, 1 H, Н(4), J = 3.5);
8.62 (d, 1 H, Н(5), J = 3.5); 9.08 (s, 1 H, Н(7))
3h
4a
4c
4d
0.19 1645 s 1140
1150
1350
1540
0.93 (t, 3 H, СН2СН2СН2СН3, J = 4.0); 1.48 (q, 2 H, СН2СН2СН2СН3, J = 5.0);
1.72 (q, 2 H, СН2СН2СН2СН3, J = 5.0); 3.78 (dt, 1 H, СН2, J1 = 6.0, J2 = 7.0);
3.84 (dt, 1 H, СН2, J1 = 6.0, J2 = 7.0); 8.20 (d, 1 H, Н(4), J = 8.0);
8.66 (d, 1 H, Н(5), J = 8.0); 9.08 (s, 1 H, Н(7))
0.86 (t, 3 H, (СН2)7СН3, J = 3.5); 1.21—1.42 (m, 10 H, СН2СН2(СН2)5СН3);
1.68—1.80 (m, 2 H, СН2СН2(СН2)5СН3); 3.74 (dt, 1 H, СН2, J1 = 5.0, J2 = 5.5);
3.85 (dt, 1 H, СН2, J1 = 5.0, J2 = 5.5); 8.18 (d, 1 H, Н(4), J = 7.5);
8.61 (d, 1 H, Н(5), J = 7.5); 9.08 (s, 1 H, Н(7))
0.22 1645 s 1130
1150
1345
1540
4f
0.18 1700 s 1120
1170
0.16 1715 s 1105
1150
1540
1350
1350
1560
7.48—7.62 (m, 5 H, Ph); 8.25 (d, 1 H, Н(6), J = 4.5); 8.65 (d, 1 H, Н(5), J = 4.5);
9.18 (s, 1 H, Н(7))
7.50—7.69 (m, 5 H, Ph); 9.15 (s, 1 H, Н(5));
4h
9.47 (s, 1 H, Н(7))
Scheme 4
Reagents and conditions: i. Cl2. ii. H2O. iii. Cl2—H2O. iv. MCPBA, CH2Cl2. v. Cl2, AcOH—H2O.

1554
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
Serebryakov and Zlotin
solvent was removed in vacuo. Cold PriOH was added, and the
precipitate that formed was filtered off, dried in air, and recrysꢀ
tallized from PriOH to give dioxide 5 (0.15 g, 36%), m.p.
281—282 °C (cf. Ref. 8: m.p. 281—283 °C).
6ꢀNitroꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1ꢀoxide (6). Gaseous
chlorine was passed for 20 min through a solution of amide 2e
(0.51 g, 2 mmol) in a mixture of CH2Cl2 (10 mL) and water
(0.5 mL). The reaction mixture was stirred at ∼20 °C for 15 min,
and the solvent was removed in vacuo. Cold PriOH was added,
and the precipitate that formed was filtered off, dried in air,
and recrystallized from PriOH to give oxide 6 (0.14 g, 34%),
m.p. 244—247 °C (cf. Ref. 8: m.p. 244—247 °C).
pound 2c with chlorine in 60% AcOH, which afꢀ
fords 2ꢀ(nꢀbutyl)ꢀ6ꢀnitroꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone
1ꢀoxide (4c).
Hence, a detailed study of the reactions of nitro deꢀ
rivatives of 2ꢀalkylthioꢀ and 2ꢀphenylthiobenzamides with
chlorine in aqueous organic solvents made it possible to
develop the new convenient synthesis of cyclic sulfꢀ
oximides of the 1,2ꢀbenzoisothiazole series.
Experimental
2ꢀEthylsulfonylꢀ4,6ꢀdinitrobenzamide (7). Gaseous chlorine
was passed at 20 °C for 10 min through a solution of amide 2g
(0.54 g, 2 mmol) in 60% AcOH (7 mL). The reaction mixture
was stirred for 15 min. The solvent and the excess of chlorine
were removed in vacuo. The resulting oil was treated with cold
PriOH, and the precipitate that formed was filtered off, dried
in air, and recrystallized from PriOH to give compound 7 (0.45 g,
70%), m.p. 175—178 °C. Found (%): C, 35.47; H, 3.03;
N, 13.74, S, 10.46. C9H9N3O7S. Calculated (%): C, 35.65;
H, 2.99; N, 13.86; S, 10.57. 1H NMR, δ: 1.29 (t, 3 H, CH3CH2,
J = 7.5 Hz); 3.63 (q, 2 H, CH3CH2, J = 7.5 Hz); 7.96,
8.24 (both br.s, 1 H each, NH); 8.88 (s, 1 H, H(3)); 9.09
(s, 1 H, H(5)).
NꢀAlkyl(aryl)ꢀ2,4ꢀdinitrobenzamides 8a,c,d,f (general proꢀ
cedure). Thionyl chloride (0.44 mL, 0.72 g, 6 mmol) and DMF
(one to two drops) were added to a suspension of 2,4ꢀdinitroꢀ
benzoic acid (0.42 g, 1.98 mmol) in anhydrous benzene (5 mL),
and the reaction mixture was refluxed for 3 h. The solvent and
the excess of SOCl2 were removed at a reduced pressure. Anhyꢀ
drous benzene (3—4 mL) was added, and the solvent was reꢀ
moved again. The 2,4ꢀdinitrobenzoyl chloride obtained was
dissolved in anhydrous benzene (5 mL) and stirred at 15 °C
while gradually adding an amine (4.2 mmol) (for 8d,f) or an
amine hydrochloride (2.1 mmol) and aqueous Na2CO3 (0.44 g,
4.2 mmol) (for 8a,c). The reaction mixture was stirred at 5 °C
for 30 min. The precipitate that formed was filtered off, washed
with distilled water (2×2 mL), dried in air, and recrystallized
from PriOH—acetone. The characteristics of compounds
8a,c,d,f are given in Tables 1 and 2.
2ꢀEthylsulfinylꢀ4ꢀnitrobenzamide (11a). A mixture of 60%
MCPBA (0.54 g, 2 mmol) and amide 2a (0.45 g, 2 mmol) in
CH2Cl2 (7 mL) was stirred at –70 °C for 4 h. The precipitate
that formed was filtered off, and the organic layer was washed
with water (4×5 mL) and dried over anhydrous MgSO4. The
solvent was removed in vacuo; the residue was triturated with
cold hexane and crystallized from PriOH to give compound
11a (0.26 g, 50%), m.p. 140—142 °C. Found (%): C, 44.78;
H, 4.31; N, 11.35; S, 13.11. C9H10N2O4S. Calculated (%):
C, 44.62; H, 4.16; N, 11.56; S, 13.24. 1H NMR, δ: 1.21 (t, 3 H,
CH3CH2, J = 6.5 Hz); 2.75, 3.29 (both m, 1 H each, CH2);
7.78 (s, 1 H, NH); 8.18 (d, 1 H, H(6), J = 6.0 Hz); 8.38 (s,
1 H, NH); 8.41 (d, 1 H, H(5), J = 6.0 Hz); 8.76 (s, 1 H, H(3)).
2ꢀEthylsulfonylꢀ4ꢀnitrobenzamide (13). A mixture of 60%
MCPBA (1.08 g, 4 mmol) and amide 2a (0.45 g, 2 mmol) in
CH2Cl2 (7 mL) was stirred at 20 °C for 4 h. The precipitate
that formed was filtered off, and the organic layer was washed
with water (4×5 mL) and dried over anhydrous MgSO4. The
solvent was removed in vacuo; the residue was triturated with
cold hexane and crystallized from PriOH to give compound 13
1
H NMR spectra were recorded on a Bruker AMꢀ300 specꢀ
trometer (300.13 MHz) in DMSOꢀd6 with Me4Si as the interꢀ
nal standard. Thinꢀlayer chromatography was carried out on
Silpearl UVꢀ250 silica gel in CCl4—acetone (4 : 1).
4,6ꢀDinitroꢀ and 2,4,6ꢀtrinitrobenzamides were prepared
according to the known procedure.14 NꢀPhenylꢀ2,4,6ꢀtriꢀ
nitrobenzamide 8h and Nꢀphenylꢀ2ꢀbenzylthioꢀ4,6ꢀdinitroꢀ
benzamide 9h were synthesized as described in Ref. 9.
2ꢀAlkylthio(arylthio)ꢀ4ꢀnitroꢀ and ꢀ4,6ꢀdinitrobenzamides
2a—h and 9a,c,d,f (general procedure). A corresponding thiol
(2.2 mmol) and Na2CO3 (0.24 g, 2.2 mmol) were added sucꢀ
cessively to a solution of amide 1a,b or 8a,c,d,f (2 mmol) in
DMF (8 mL). The reaction mixture was stirred at 20 °C for
5—8 h (in the case of thiophenol, the reaction was carried out
in an atmosphere of nitrogen) until the starting amide was
completely consumed (TLC) and then acidified with 0.05 M
HCl (15 mL). The precipitate that formed was filtered off,
washed with water (2×5 mL), dried in air, and recrystallized
from PriOH. The yields, melting points, and elemental analysis
data for the compounds obtained are given in Table 1. Their
1H NMR spectra are presented in Table 2.
1ꢀAlkyl(aryl)ꢀ4ꢀnitroꢀ and 4,6ꢀdinitroꢀ1ꢀphenylꢀ1,2ꢀbenzoꢀ
isothiazolꢀ3ꢀone 1ꢀoxides 3a,b,d,f,h (general procedure). Gasꢀ
eous chlorine was passed at 20 °C for 10 min through a solution
of an amide (2a,b,d,f,h or 11a) (2 mmol) in 60% AcOH (7 mL),
and the reaction mixture was stirred for 10 min. The solvent
and the excess of chlorine were removed in vacuo. Cold PriOH
(3—5 mL) was added, and the precipitate that formed was
filtered off, dried in air, and recrystallized from PriOH. The
yields, melting points, and elemental analysis data for comꢀ
pounds 3a,b,d,f,h are given in Table 1. Their retention factors,
1H NMR and IR spectra are presented in Table 3.
2ꢀAlkyl(aryl)ꢀ4ꢀnitroꢀ and 4,6ꢀdinitroꢀ2ꢀphenylꢀ1,2ꢀbenzoꢀ
isothiazolꢀ3ꢀone 1ꢀoxides 4a,c,d,f,h (general procedure). Gasꢀ
eous chlorine was passed at 20 °C for 10 min through a solution
of an amide (9a,c,d,f,h) (2 mmol) in a mixture of CH2Cl2
(10 mL) and water (0.5 mL), and the reaction mixture was
stirred for 15 min. The solvent and the excess of chlorine were
removed in vacuo. Cold PriOH (3—5 mL) was added, and the
precipitate that formed was filtered off, dried in air, and recrysꢀ
tallized from PriOH. The yields, melting points, and elemental
analysis data for compounds 4a,c,d,f,h are given in Table 1.
1
Their retention factors, H NMR and IR spectra are presented
in Table 3.
6ꢀNitroꢀ1,2ꢀbenzoisothiazolꢀ3ꢀone 1,1ꢀdioxide (5). Gaseous
chlorine was passed for 15 min through a vigorously stirred
solution of amide 2e (0.51 g, 2 mmol) in 60% AcOH (7 mL).
The reaction mixture was stirred at ∼20 °C for 25 min, and the

Nitro derivatives of cyclic sulfoximides
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 8, August, 2002
1555
(0.33 g, 61%), m.p. 152—155 °C. Found (%): C, 41.75; H, 3.98;
N, 10.98; S, 12.62. C9H10N2O5S. Calculated (%): C, 41.86;
H, 3.90; N, 10.85; S, 12.42. 1H NMR, δ: 1.36 (t, 3 H, CH3CH2,
J = 6.5 Hz); 3.82 (q, 2 H, CH3CH2, J = 7.0 Hz); 7.78 (s, 1 H,
NH); 8.18 (d, 1 H, H(6), J = 6.0 Hz); 8.38 (s, 1 H, NH); 8.41
(d, 1 H, H(5), J = 6.0 Hz); 8.76 (s, 1 H, H(3)).
8. E. A. Serebryakov, P. G. Kislitsin, V. V. Semenov, and
S. G. Zlotin, Synthesis, 2001, 1659.
9. S. G. Zlotin, P. G. Kislitsin, A. V. Samet, E. A. Serebryakov,
L. D. Konyushkin, V. V. Semenov, A. C. Buchanan, III,
and A. A. Gakh, J. Org. Chem., 2000, 65, 8430.
10. A. Gordon and R. Ford, Chemist´s Companion. A Handbook
of Practical Data, Techniques, and References, Wiley Interꢀ
science, New York—London—Toronto, 1972.
11. K. SchaffnerꢀSabba, H. Tomaselli, B. Henrici, and
H. Renfroe, J. Org. Chem., 1977, 42, 952.
References
1. P. D. Kennewell and J. B. Taylor, Chem. Soc. Rev.,
1975, 4, 189.
12. D. Carr, T. Siden, and R. Turner, Tetrahedron Lett.,
1969, 477.
2. P. Stoss and G. Satzinger, Chem. Ber., 1972, 105, 2575.
3. Belg. Pat. 814400, Ger. Offen 2,321,786 (1974); Chem. Abstr.,
1975, 82, 73035.
4. DE 1914016 1970; Chem. Abstr., 1971, 74, 22822.
5. T. Williams and D. Cram, J. Org. Chem., 1973, 38, 20.
6. T. Williams and D. Cram, J. Am. Chem. Soc., 1971, 93, 7333.
7. P. Stoss and G. Satzinger, Angew. Chem., Int. Ed. Engl.,
1971, 10, 76.
13. M. Chan and M. Garst, J. Chem. Soc., Chem. Commun.,
1991, 540.
14. A. J. Gerasyuto, S. G. Zlotin, and V. V. Semenov, Syntheꢀ
sis, 2001, 300.
Received December 13, 2001;
in revised form March 11, 2002