Synthetic study of substituted arylsulfonylphenylbenzamides

Article abstract of DOI:10.1081/SCC-200046496

For the structure-activity relationship, a series of substituted arylsulfonyl-phenylbenzamides is reported.

Full text of DOI:10.1081/SCC-200046496

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Synthetic Study of Substituted
Arylsulfonylphenylbenzamides
Denghuang Gong a , Jinfeng Li a , Chengye Yuan a &
Junying Yuan b
a Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, Shanghai, China
b Department of Cell Biology, Harvard Medical
School, Boston, MA, USA
Available online: 05 Aug 2006
To cite this article: Denghuang Gong, Jinfeng Li, Chengye Yuan & Junying Yuan
(2005): Synthetic Study of Substituted Arylsulfonylphenylbenzamides, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 35:1, 55-66
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Synthetic Communicationsw, 35: 55–66, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200046496
Synthetic Study of Substituted
Arylsulfonylphenylbenzamides
*
Denghuang Gong, Jinfeng Li and Chengye Yuan
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai, China
*
Junying Yuan
Department of Cell Biology, Harvard Medical School, Boston, MA, USA
Abstract: For the structure-activity relationship, a series of substituted arylsulfonyl-
phenylbenzamides is reported.
Keywords: Aryl sulfones, benzomides, structure-activity relationship
INTRODUCTION
Aryl sulfones are important synthetic targets due to their chemical properties
and biological activities.[1–4] Some of them exhibit important biological
properties, such as antiulcer,[5] antitubercular,[6] anticholesteremic,[7] anti-
microbial,[8] and antibiotic[9] activities. Diaryl sulfones have been shown to
inhibit the HIV-1 reverse transcriptase and represent an emerging class of
substances able to address the toxicity and resistance problems of nucleoside
inhibitors.[10–12] A class of substituted arylsulfonylphenylbenzamides (known
as BH3I2s) was discovered by Junying Yuan’s group in high-throughput
fluorescence polarization screen of a 16 320-member small-molecule library
and had been recently reported to have a function similar to Bak BH3
Received in Japan August 19, 2004
*
These authors contributed equally.
*
Address correspondence to Chengye Yuan Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, Shanghai, China. Fax: þ86-21-6416-
6128; E-mail: yuancy@mail.sioc.ac.cn

56
D. Gong et al.
peptide (Figure 1). They induce apoptosis by disrupting interactions mediated
by the BH3 domain, between pro-apoptotic and anti-apoptotic members of the
Bcl-2 family,[13] and induce rapid damage to the inner mitochondria1
membrane prior to the cytochrome c release from mitochondria.[14] Synthesis
of aryl sulfones are well documented,[15–20] but the preparation of BH3I2s
are not found. In this paper, we wish to present a facile and convenient
synthesis of BH3I2 derivatives to investigate their biological activities.
RESULTS AND DISCUSSION
Our synthetic route leading to BH3I2 derivatives is based on the following
sequence of reactions as shown in Scheme 1.
Cuprous thiophenolates 1 were readily prepared from substituted thiophe-
nols with cuprous oxide in ethanol under refluxing, and reaction of cuprous
thiophenolates with substituted 3-bromonitrobenzene, quinoline, and
pyridine at about 2208C to give the corresponding aryl thiothers 2.[21] The
oxidation of sulfides is a general method for preparation of sulfones, and
here the complex of urea and hydrogen peroxide,[22] a safe, mild, and
efficient oxidizing agent, was used as the oxidant at room temperature in
this step, and the desired aryl sulfones 3 were obtained in high yields.
Reduction of the aryl sulfones 3 in the presence of iron powder and drops
of concentrated hydrochloric acid in ethanol under typical reduction
procedure[23] to give the corresponding substituted benzenesulfonyl anilines
4 in good yields. Chlorination of substituted salicylic acids by phosphorus tri-
chloride in nitrobenzene gave substituted 2-hydroxybenzoyl chlorides, and
Figure 1. Structure of BH3I2 family.

Synthetic Study of Substituted Arylsulfonylphenylbenzamides
57
Scheme 1.
they reacted with benzenesulfonyl anilines 4 to afford the desired products,
BH3I2 derivatives 5 in moderate yields (Table 1).
In conclusion, we have described a simple and convenient procedure for
the preparation of BH3I2 derivatives from substituted thiophenols. All the
1
new compounds were characterized by their HNMR, mass spectral data,
and elemental analyses. To the best of our knowledge, most of these
compounds have not been reported, and their biological activities are
currently under investigations.
EXPERIMENTAL
Melting points are uncorrected. IR spectra were taken on a Shimadzu-440
1
spectrometer. The H NMR spectra were recorded in CDCl3 solution on a

58
D. Gong et al.
Table 1. Preparation of Compounds 5
Compounds
R1
R2
R3
R4
R5
Yield (%)
5a
5b
5c
5d
5e
5f
H
H
H
H
H
H
Cl
Br
I
H
H
H
65
41
50
56
58
52
60
43
46
49
51
53
43
48
52
55
37
39
36
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
OH
H
H
Cl
Br
I
H
H
H
H
H
H
H
H
Cl
Br
I
Cl
Br
Cl
Br
I
5g
5h
5i
H
H
H
Cl
Cl
Cl
Cl
Cl
H
H
5j
H
5k
5l
H
H
H
Cl
Br
I
Cl
Br
Cl
Br
I
H
5m
5n
5o
5p
5q
5r
5s
Cl
Cl
Cl
Cl
Cl
Br
Br
H
H
H
H
Cl
Cl
Br
Cl
Cl
Cl
Br
Cl
Cl
Cl
Bruker AM-300 or Varian-360L instrument using TMS as an internal
standard. EIMS data were obtained on a HP5989A mass spectrometer.
HRMS were recorded on a Telsa FTMS spectrometer. The elemental
analyses were performed at the Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences. All solvents were dried prior to use by
standard procedures.
General Procedure for Synthesis of Compounds 2
A mixture of substituted 3-bromonitrobenzene (0.01 mol), cuprous thiopheno-
late (0.01 mol), pyridine (1.5 mL), and quinoline (10 mL) was heated with
stirring in an oil bath at about 2208C for 2h. The hot solution was then
poured into cracked ice and excess conc. hydrochloric acid, standing for
about 2h. The mixture was extracted with ethyl ether, and the combined
organic layers were dried with anhyd. MgSO4, concentrated under reduced
pressure and purified by column chromatography on silica gel (petroleum
ether) to afford the pure product.
1-Nitro-3-phenylthiobenzene (2a) Yellow solid; mp 43–448C (lit.[24]
1
42.58C); yield, 73%. H NMR (CDCl3) d 7.99–8.04 (m, 2H), 7.39–7.51

Synthetic Study of Substituted Arylsulfonylphenylbenzamides
59
(m, 7H). MS, m/e (%): 231 (Mþ, 100), 232 (Mþ þ 1, 18.76) 215 (5.12), 184
(76.61).
4-Chloro-1-nitro-3-phenylthiobenzene (2b) Yellow solid; mp 86–888C;
yield, 80%. IR (KBr) n: 3109, 1563, 1517, 1473, 1445, 1341, 1295,
1
1133 cm21. H NMR (CDCl3) d 7.90 (dd, 1H, J ¼ 2.7, 8.7 Hz), 7.50–7.58
(m, 7H). MS, m/e (%): 265 (Mþ ¼ , 70.55), 267 (Mþ þ 2, 28.64), 184
(100). HRMS calcd for C12H8ClNO2S: 264.9964. Found: 264.9984.
3-((4-Chlorophenyl)thio)-1-nitrobenzene (2c) Yellow solid; mp 70–
728C; yield, 78%. IR (KBr) n: 3105, 1604, 1473, 1350, 1307 cm21 1H
.
NMR (CDC13) d 8.03–8.06 (m, 2H), 7.27–7.52 (m, 6H). MS, m/e (%):
265 (Mþ, 100), 267 (Mþ þ 2, 38.02), 184 (87.01). HRMS calcd for
C12H8C1NO2S: 264.9964. Found: 264.9986.
4-Chloro-3-((4-chlorophenyl)thio)-1-nitrobenzene (2d) Yellow solid; mp
116–1188C; yield, 76%. IR (KBr) n: 1572, 1476, 1445, 1388, 1343,
1
1294 cm21. H NMR (CDCl3) d 7.94 (dd, 1H, J ¼ 2.4, 8.7 Hz), 7.64 (d, 1H,
J ¼ 3.0 Hz), 7.53 (d, 1H, J ¼ 8.4 Hz), 7.47–7.48 (m, 4H). MS, m/e (%):
300 (Mþ, 10.35), 301 (Mþ þ l, 49.05), 299 (Mþ 2 1, 71.86), 218 (100).
HRMS calcd for C12H7Cl2NO2S: 298.9575. Found: 298.9587.
4-Chloro-3-((4-bromophenyl)thio)-1-nitrobenzene (2e) Yellow solid; mp
120–1218C; yield, 66%. R (KBr) n: 1575, 1513, 1475, 1444, 1386, 1344,
1
1293 cm21. H NMR (CDCl3) d 7.96 (dd, 1H, J ¼ 2.7, 9.0 Hz), 7.39–7.67
(m, 6H). MS, m/e (%): 345 (Mþ, 20.93), 343 (Mþ 2 1, 16.06), 299 (35.31),
265 (24.98), 218 (100), 184 (81.47). HRMS calcd for C12H7BrClNO2S:
342.9069. Found: 342.9082.
General Procedure for Synthesis of Compounds 3
To a solution of urea hydrogen peroxide (0.06 mol), trifluoroacetic anhydride
(0.04 mol) and acetonitrile (5 mL) was added with stirring the mixture of
compound 2 (0.01 mol) and acetonitrile (5 mL). The progress of the reaction
was monitored by TLC. After completion of oxidation, water (10 mL) was
added to the reaction solution, and the aqueous phase was extracted with
dichloromethane. The combined organic layers were washed with water,
then dried with anhyd. MgSO4, concentrated under reduced pressure and
purified by column chromatography on silica gel (petroleum ether : ethyl
acetate ¼ 10 : 1) to afford the pure product.
1-Nitro-3-benzenesulfonylbenzene (3a) White solid; mp 81–828C (lit.[25]
1
79–818C); yield, 91%. H NMR (CD3COCD3) d 8.73 (d, 1H, J ¼ 1.5 Hz),
8.51–8.55 (m, 1H), 8.42 (dd, 1H, J ¼ 0.9, 8.1 Hz), 8.09 (d, 2H, J ¼ 7.8 Hz),
7.96 (t, 1H, J ¼ 7.8 Hz), 7.65–7.75 (m, 3H). MS, m/e (%): 263 (Mþ, 100),
264 (Mþ þ 1, 14.62), 170 (81.90), 77 (83.19).
4-Chloro-1-nitro-3-benzenesulfonylbenzene (3b) White solid; mp
166–1688C (lit.[26] 1748C); yield, 93%. 1H NMR (CD3COCD3) d 9.11

60
D. Gong et al.
(d, 1H, J ¼ 2.7 Hz), 8.55 (dd, 1H, J ¼ 2.7, 8.4 Hz), 8.08 (dd, 2H, J ¼ 1.2,
8.4 Hz), 7.92 (d, 1H, J ¼ 9.0 Hz), 7.78 (d, 1H, J ¼ 7.5 Hz), 7.65–7.71
(m, 2H). MS, m/e (%): 297 (Mþ, 26.05), 204 (18.11), 77 (100).
3-(4-Chlorobenzenesulfonyl)-1-nitrobenzene (3c) White solid; mp 137–
1398C (lit.[26] 139–1408C); yield, 90%. 1H NMR (CD3COCD3) d 8.61
(t, 1H, J ¼ 1.8 Hz), 8.40–8.43 (m, 1H), 8.30 (dd, 1H, J ¼ 1.2, 7.8 Hz), 7.98
(dd, 2H, J ¼ 1.5, 9.0 Hz), 7.82–7.87 (m, 1H), 7.57 (dd, 2H, J ¼ 1.5,
9.0 Hz). MS, m/e (%): 297 (Mþ, 52.34), 170 (30.31), 159 (37.97), 127 (100).
4-Chloro-3-(4-chlorobenzenesulfonyl)-1-nitrobenzene (3d) White solid;
mp 152–1548C; yield, 96%. IR (KBr) n: 3091, 1598, 1577, 1530, 1479,
1
1394, 1346, 1163 cm21. H NMR (CD3COCD3) d 8.97 (d, 1H, J ¼ 2.7 Hz),
8.43 (dd, 1H, 2.7, 8.4 Hz), 7.97 (d, 2H, J ¼ 8.7 Hz), 7.80 (d, 1H,
J ¼ 8.7 Hz), 7.59 (d, 2H, J ¼ 9.0 Hz). MS, m/e (%): 331 (Mþ, 22.63), 333
(Mþ þ 2, 15.39), 175 (25.41), 159 (35.99, 127 (100), 111(86.34). HRMS
calcd for C12H7Cl2NO4S: 330.9473. Found: 330.9482.
4-Chloro-3-(4-bromobenzenesulfonyl)-1-nitrobenzene (3e) White solid;
mp 122–1238C; yield, 88%. IR (KBr) n: 3092, 1599, 1572, 1529, 1474,
1
1392, 1344, 1162 cm21. H NMR (CD3COCD3) d 9.10 (d, 1H, J ¼ 2.7 Hz),
8.56 (dd, 1H, J ¼ 2.7, 8.7 Hz), 8.10 (d, 1H, J ¼ 8.7 Hz), 8.02 (dd, 1H,
J ¼ 2.1, 8.4 Hz), 7.94 (d, 1H, J ¼ 8.7 Hz), 7.86–7.89 (m, 1H), 7.72 (d, 1H,
J ¼ 8.4 Hz). MS, m/e (%): 376 (Mþ, 3.01), 377 (Mþ þ 1, 26.78), 331
(13.26), 219 (19.36), 171 (53.86), 75 (100). HRMS calcd for
C12H7BrC1NO4S: 374.8968. Found: 374.8972.
General Procedure for Synthesis of Compounds 4
A solution of compound 3 (0.001 mol), iron powder (0.0045 mol), ethanol
(2 mL), water (0.5 mL), and three drops of conc. hydrochloric acid was
refluxed for about 3h, and the progress of the reaction was monitored by
TLC. After completion of reduction, water (10 mL) was added to the
reaction solution, and pH was adjusted to 8 by potassium carbonate. The
aqueous phase was extracted with dichloromethane. The combined organic
layers were washed with water, then dried with anhyd. MgSO4, concentrated
under reduced pressure and purified by column chromatography on silica gel
(petroleum ether : ethyl acetate ¼ 5 : 1) to afford the pure product.
1-Amino-3-benzenesulfonylbenzene (4a) White solid; mp 115–1168C
1
(lit.[27] 1178C); yield, 73%. H NMR (CD3COCD3) d 7.92–7.95 (m, 2H),
7.59–7.65 (m, 3H), 7.22–7.27 (m, 2H), 7.12–7.16 (m, 1H), 6.87–6.91
(m, 1H), 5.22 (s, 2H, NH2). MS, m/e (%): 233 (Mþ, 100), 234 (Mþ þ l,
14.79), 169 (15.99), 125 (20.35).
4-Chloro-1-amino-3-benzenesulfonylbenzene (4b) White solid; mp 180–
1818C; yield, 82%. IR (KBr) n: 3467, 3381, 1626, 1597, 1584, 1471, 1450,
1
1310, 1158 cm21. H NMR (CD3COCD3) d 7.92–7.95 (m, 2H), 7.59–7.70

Synthetic Study of Substituted Arylsulfonylphenylbenzamides
61
(m, 4H), 7.17 (dd, 1H, J ¼ 1.8, 8.7 Hz), 6.91 (dd, 1H, J ¼ 3.0, 8.7 Hz), 5.41
(s, 2H, NH2). MS, m/e (%): 267 (Mþ, 100), 269 (Mþ þ 2, 37.16), 203
(5.60), 125 (34.91). HRMS calcd for C12H10C1NO2S: 267.0121. Found:
267.0107.
3-(4-Chlorobenzenesulfonyl)-1-aminobenzene (4c) White solid; mp 135–
1368C[28] yield, 75%. 1H NMR (CD3COCD3) d 7.93 (dd, 2H, J ¼ 2.1, 6.9 Hz),
7.63 (dd, 2H, J ¼ 2.1, 6.9 Hz), 7.27 (d, 1H, J ¼ 7.8 Hz), 7.24 (d, 1H,
J ¼ 1.8 Hz), 7.12–7.16 (m, 1H), 6.90–6.93 (m, 1H), 5.23 (s, 2H, NH2).
MS, m/e (%): 267 (Mþ, 100), 269 (Mþ þ 2, 37.75), 203 (24.54).
4-Chloro-3-(4-chlorobenzenesulfonyl)-1-aminobenzene (4d) White solid;
mp 176–1788C; yield, 76%. IR (KBr) n: 3486, 3383, 1616, 1597, 1584, 1474,
1
1423, 1307, 1283, 1160, 1149 cm21. H NMR (CD3COCD3) d 7.81 (dd, 2H,
J ¼ 2.1, 6.6 Hz), 7.53 (dd, 2H, J ¼ 2.1, 6.6 Hz), 7.50 (d, 1H, J ¼ 3.0 Hz), 7.05
(d, 1H, J ¼ 8.4 Hz), 6.80 (dd, 1H, J ¼ 2.7, 8.4 Hz), 5.30 (s, 2H, NH2). MS, m/e
(%): 302 (Mþ, 15.43), 303 (Mþ þ 1, 68.51), 301 (Mþ 2 1, 100), 159 (35.94).
HRMS calcd for C12H9Cl2NO2S: 300.9731. Found: 300.9717.
4-Chloro-3-(4-bromobenzenesulfonyl)-1-aminobenzene (4e) White solid;
mp 174–1758C; yield, 70%. IR (KBr) n: 3484, 3382, 1617, 1597, 1560, 1472,
1
1390, 1310, 1281, 1159, 1148 cm21. H NMR (CD3COCD3) d 7.80–7.88
(m, 3H), 7.63–7.65 (m, 2H), 7.18 (d, 1H, J ¼ 8.4 Hz), 6.94 (dd, 1H,
J ¼ 2.7, 8.4 Hz), 5.44 (5.2H, NH2). MS, m/e (%): 346 (Mþ, 12.66), 347
(Mþ þ 1, base), 345 (Mþ 2 1,77.50), 301 (68.81), 203 (22.12). HRMS
calcd for C12H9BrClNO2S: 344.9226. Found: 344.9243.
General Procedure for Synthesis of Compounds 5
A solution of substituted salicylic acid (0.5 mmol) and PCl3 (0.25 mmol) in
chlorobenzene (1.5 mL) was refluxed for 30 min and then cooled to 40 8C.
Compound 4 (0.5 mmol) in chlorobenzene (1.5 mL) was added and the
mixture was refluxed for 5h. Solvent was removed under reduced pressure
and the resulting residue was recrystallized from ethanol to give pure product.
N-(3-phenylsulfonyl)phenylbenzamide (5a) White solid; mp 140–1418C.
IR (KBr) n: 3340, 3060, 1677, 1656, 1596, 1535, 1479, 1447, 1420, 1304,
1152 cm21 1H NMR (CD3COCD3) d 9.91 (s, 1H, NH), 8.63 (t, 1H,
.
J ¼ 1.8 Hz), 8.13–8.17 (m, 1H), 7.99–8.05 (m, 4H), 7.73–7.76 (m, 1H),
7.47–7.65 (m, 7H). MS, m/e (%): 337 (Mþ, 34.99), 338 (Mþ þ 1, 8.15),
220 (14.70), 205 (59.27), 105 (100). Anal. Calcd for C19H15NO3S (337.40):
C, 67.64; H, 4.48; N, 4.15. Found: C, 67.70; H, 4.42; N, 3.87.
2-hydroxy-N-(3-phenylsulfony)phenylbenzamide (5b) White solid; mp
158–1598C. IR (KBr) n: 3304, 3075, 1650, 1631, 1617, 1594, 1554, 1477,
1
1456, 1423, 1321, 1233, 1151 cm21. H NMR (CD3COCD3) d 11.87 (s, 1H,
OH), 10.18 (s, 1H, NH), 8.47 (t, 1H, J ¼ 1.8 Hz), 8.00–8.10 (m, 4H), 7.76–
7.80 (m, 1H), 7.61–7.70 (m, 4H), 7.47–7.53 (m, 1H), 6.94–7.00 (m, 2H).

62
D. Gong et al.
MS, m/e (%): 353 (Mþ, 46.04), 354 (Mþ þ 1, 10.27), 233 (100), 121 (67.26).
Anal. Calcd for C19H15NO4S (353.40): C, 64.58; H, 4.28; N, 3.96. Found: C,
64.93; H, 4.23; N, 3.73.
3,5-dichloro-2-hydroxy-N-(3-phenylsulfonyl)phenylbenzamide (5c) White
solid; mp 168–1708C. IR (KBr) n: 3364, 3071, 1700, 1647, 1600, 1580,
1541, 1481, 1449, 1355, 1328, 1305, 1244, 1154cm21
.
1H NMR
(CD3COCD3) d 10.19 (s, 1H, NH), 8.44 (t, 1H, J ¼ 2.1 Hz), 7.99–8.08
(m, 4H), 7.79–7.82 (m, 1H), 7.60–7.66 (m, 5H). MS, m/e (%): 422 (Mþ,
4.18), 421 (Mþ 2 1, 14.62), 233 (100), 189 (26.74). Anal. Calcd for
C19H13Cl2NO4S (422.29): C, 54.04; H, 3.10; N, 3.32. Found: C, 53.80; H,
3.36; N, 2.93.
3,5-dibromo-2-hydroxy-N-(3-phenylsulfonyl)phenylbenzamide (5d) White
solid; mp 187–1898C. IR (KBr) n: 3481, 3333, 1650, 1596, 1478, 1446,
1
1427, 1404, 1354, 1305, 1255, 1186, 1148cm21. H NMR (CD3COCD3)
d 12.85 (s, 1H, OH), 10.22 (s, 1H, NH), 8.42 (s, 1H), 8.22 (d, 1H,
J ¼ 2.1 Hz), 8.08 (dd, 1H, J ¼ 0.9, 8.7 Hz), 7.99–8.03 (m, 2H), 7.96–7.97
(m, 1H), 7.81–7.85 (m, 1H), 7.62–7.71 (m, 4H). MS, m/e (%): 511 (Mþ,
7.34), 513 (Mþ þ 2, 4.02), 279 (18.65), 233 (100). HRMS calcd for
C19H13Br2NO4S: 508.8927. Found: 508.8855.
3,5-diiodo-2-hydroxy-N-(3-phenylsulfonyl)phenylbenzamide (5e) White
solid; mp 126–1278C. IR (KBr) n: 3503, 3064, 1644, 1596, 1544, 1478,
1447, 1427, 1397, 1351, 1303, 1256, 1183, 1146 cm21
.
1H NMR
(CD3COCD3) d 12.94 (s, 1H, OH), 10.10 (s, 1H, NH), 8.27 (d, 1H,
J ¼ 1.8 Hz), 8.20 (d, 1H, J ¼ 1.8 Hz), 8.14 (d, 1H, J ¼ 1.8 Hz), 7.86–7.94
(m, 3H), 7.67–7.71 (m, 1H), 7.48–7.57 (m, 4H). MS, m/e (%): 605 (Mþ,
16.08), 373 (22.32), 233 (100). Anal. Calcd for C19H13I2NO4S (605.19): C,
37.71; H, 2.17; N, 2.31. Found: C, 37.80; H, 2.78; N, 2.13.
5-chloro-2-hydroxy-N-(3-phenylsulfonyl)phenylbenzamide (5f) White
solid; mp 186–1888C. IR (KBr) n: 3203, 3064, 1645, 1607, 1594, 1550,
1477, 1448, 1422, 1359, 1330, 1309, 1244, 1153, 1107 cm21 1H NMR
.
(CD3COCD3) d 11.86 (s, 1H, OH), 10.14 (s, 1H, NH), 8.47 (t, 1H,
J ¼ 2.1 Hz), 7.99–8.08 (m, 4H), 7.79 (dd, 1H, J ¼ 0.8, 8.1 Hz), 7.62–7.70
(m, 4H), 7.49 (dd, 1H, J ¼ 2.7, 9.0 Hz), 7.02 (dd, 1H, J ¼ 2.4, 8.7 Hz). MS,
m/e (%): 387 (Mþ, 19.28), 233 (100), 155(32.76). Anal. Calcd for
C19H14ClNO4S (387.84): C, 58.84; H, 3.64; N, 3.61. Found: C, 58.81; H,
3.71; N, 3.37.
5-bromo-2-hydroxy-N-(3-phenylsulfonyl)phenylbenzamide (5g) White
solid; mp 188–1898C. IR (KBr) n: 3403, 3189, 1645, 1594, 1485, 1477,
1
1447, 1420, 1330, 1300, 1219, 1152, 1101 cm21. H NMR (CD3COCD3) d
11.90 (s, 1H, OH), 10.15 (s, 1H, NH), 8.47 (t, 1H, J ¼ 2.1 Hz), 8.17 (d, 1H,
J ¼ 2.1 Hz), 7.99–8.08 (m, 3H), 7.78–7.81 (m, 1H), 7.61–7.70 (m, 5H),
6.97 (d, 1H, J ¼ 8.7 Hz). MS, m/e (%): 432 (Mþ, 2.84), 433 (Mþ 2 1,
12.64), 431 (Mþ þ 1, 12.59), 233 (100). Anal. Calcd for C19H14BrNO4S
(432.30): C, 52.79; H, 3.26; N, 3.24. Found: C, 53.03; H, 3.73; N, 3.06.

Synthetic Study of Substituted Arylsulfonylphenylbenzamides
63
3,5-dichloro-2-hydroxy-N-((4-chloro-3-phenylsulfonyl)phenyl) benzamide
(5h) White solid; mp 269–2718C. IR (KBr) n: 3368, 1650, 1586, 1527, 1467,
1
1446, 1390, 1356, 1308, 1253, 1157, 1140cm21. H NMR (CD3COCD3) d
12.64 (s, 1H, OH), 10.43 (s, 1H, NH), 8.78 (d, 1H, J ¼ 3.0 Hz), 8.19 (dd, 1H,
J ¼ 1.8, 8.7 Hz), 8.12 (d, 1H, J ¼ 2.4 Hz), 7.98–8.01 (m, 2H), 7.73–7.75
(m, 2H), 7.61–7.69 (m, 3H). MS, m/e (%): 456 (Mþ, 1.74), 457 (Mþ þ 1,
7.65), 455 (Mþ 2 1, 7–44), 267 (100), 189 (35.78). HRMS calcd for
C19H12Cl3NO4S: 454.9547. Found: 454.9522.
3,5-dibromo-2-hydroxy-N-((4-chloro-3-phenylsulfonyl)phenyl) benzamide
(5i) White solid; mp 262–2638C. IR (KBr) n: 3388, 1648, 1583, 1526, 1467,
1
1442, 1390, 1353, 1307, 1253, 1184, 1156cm21. H NMR (CD3COCD3)
d 8.78 (dd, 1H, J ¼ 1.2, 2.7 Hz), 8.13–8.15 (m, 1H), 8.03–8.08 (m, 1H),
7.85–7.88 (m, 3H), 7.48–7.56 (m, 4H). MS, m/e (%): 545 (Mþ, 6.39), 267
(100). HRMS calcd for C19H12Br2ClNO4S: 542.8537. Found: 542.8444.
3,5-diiodo-2-hydroxy-N-((4-chloro-3-phenylsulfonyl)phenyl)benzamide (5j)
White solid; mp 262–2648C. IR (KBr) n: 3373, 1643, 1581, 1521, 1466, 1436,
1
1390, 1350, 1315, 1306, 1278, 1154 cm21. H NMR (CD3COCD3) d 13.01
(s, 1H, OH), 10.38 (s, 1H, NH), 8.74 (d, 1H, J ¼ 2.7 Hz), 8.38 (d, 1H,
J ¼ 2.1 Hz), 8.30 (d, 1H, J ¼ 1.5 Hz), 8.16 (dd, 1H, J ¼ 3.0, 9.0 Hz),7.98–8.01
(m, 2H), 7.60–7.75 (m, 4H). MS, m/e (%): 639 (Mþ, 5.50), 513 (10.83), 373
(16.85), 267 (100). Anal. Calcd for C19H12ClI2NO4S (639.64): C, 35.68; H,
1.89; N, 2.19. Found: C, 35.65; H, 2.19; N, 2.05.
5-chloro-2-hydroxy-N-((4-chloro-3-phenylsulfonyl)phenyl)benzamide (5k)
White solid; mp 230–2328C. IR (KBr) n: 3379, 1653, 1607, 1585, 1527,
1
1473, 1448, 1316, 1281, 1155cm21. H NMR (CD3COCD3) d 11.75 (s, 1H,
OH), 10.30 (s, 1H, NH), 8.66 (dd, 1H, J ¼ 1.5, 2.7 Hz), 8.03–8.07 (m, 1H),
7.98 (t, 1H, J ¼ 2.1 Hz), 7.85–7.89 (m, 2H), 7.37–7.59 (m, 5H), 6.92 (dd,
1H, J ¼ 1.5, 8.7 Hz). MS, m/e (%): 422 (Mþ, 1.58), 421 (Mþ 2 1, 7.11), 267
(100). Anal. Calcd for C19H13Cl2NO4S (422.29): C, 54.04; H, 3.10; N, 3.32.
Found: C, 53.54; H, 3.27; N, 3.14.
5-bromo-2-hydroxy-N-((4-chloro-3-phenylsulfonyl)phenyl)benzamide (5l)
White solid; mp 228–2308C. IR (KBr) n: 3358, 1651, 1606, 1582, 1527,
1
1480, 1448, 1315, 1307, 1155cm21. H NMR (CD3COCD3) d 11.73 (s, 1H,
OH), 10.16 (s, 1H, NH), 8.66 (dd, 1H, J ¼ 0.9, 2.7 Hz), 8.02–8.09 (m, 2H),
7.85–7.89 (m, 2H), 7.45–7.59 (m, 5H), 6.88 (dd, 1H, J ¼ 0.9, 8.7 Hz). MS,
m/e (%): 467 (Mþ, 1.58), 465 (Mþ 2 2, 7.63), 267(100). HRMS calcd for
C19H13BrClNO4S: 464.9437. Found: 464.9442.
3,5-dichloro-2-hydroxy-N-(3-(4-chlorophenylsulfonyl)phenyl)benzamide
(5m) White solid; mp 215–2168C. IR (KBr) n: 3347, 1653, 1592, 1539, 1477,
1
1448, 1357, 1317, 1305, 1145 cm21. H NMR (CD3COCD3) d 10.12 (s, 1H,
NH), 8.31 (t, 1H, J ¼ 2.1 Hz), 7.87–7.95 (m, 4H), 7.68–7.73 (m, 1H),
7.53–7.58 (m, 4H). MS, m/e (%): 457 (Mþ, 15.71), 455 (Mþ 2 2, 15.43),
313 (17.56), 267 (100), 189 (47.09). HRMS calcd for C19H12Cl3NO4S:
454.9547. Found: 454.9470.

64
D. Gong et al.
3,5-dibromo-2-hydroxy-N-(3-(4-chloropheny1sulfonyl)phenyl)benzamide
(5n) White solid; mp 236–2388C. IR (KBr) n: 3347, 1653, 1592, 1539, 1477,
1
1448, 1357, 1317, 1305, 1145 cm21. H NMR (CD3COCD3) d 12.69 (s, 1H,
OH), 10.12 (s, 1H, NH), 8.30 (d, 1H, J ¼ 1.8 Hz), 8.07 (d, 1H,
J ¼ 2.7 Hz),7.93–7.96 (m, 1H), 7.87–7.90 (m, 2H), 7.79–7.82 (m, 1H),
7.68–7.72 (m, 1H), 7.52–7.58 (m, 3H). MS, m/e (%): 545 (Mþ, 11.93),
311 (12.52), 279 (35.28), 267 (100). HRMS calcd for C19H12Br2ClNO4S:
542.8537. Found: 542.8522.
3,5-diiodo-2-hydroxy-N-(3-(4-chlorophenylsulfonyl)phenyl)benzamide (5o)
White solid; mp 226–2278C. IR (KBr) n: 3346, 1647, 1591, 1573, 1530, 1476,
1
1394, 1316, 1278, 1147 cm21. H NMR (CD3COCD3) d 13.06 (s, 1H, OH),
10.25 (s, 1H, NH), 8.41 (t, 1H, J ¼ 2.1 Hz), 8.32 (d, 1H, J ¼ 1.8 Hz), 8.27
(d, 1H, J ¼ 2.1 Hz), 7.92–8.08 (m, 3H), 7.81–7.86 (m, 1H), 7.65–7.71
(m, 3H). MS, m/e (%): 639 (Mþ, 11.74), 623 (1.46), 373 (34.60), 267 (100),
254 (64.35). Anal. Calcd for C19H12ClI2NO4S (639.64): C, 35.68; H, 1.89; N,
2.19. Found: C, 35.58; H, 2.13; N, 2.00.
5-chloro-2-hydroxy-N-(3-(4-chlorophenylsulfonyl)phenyl)benzamide (5p)
White solid; mp 222–2248C. IR (KBr) n: 3246, 1643, 1618, 1597, 1561,
1
1475, 1430, 1392, 1323, 1279, 1157cm21. H NMR (CD3COCD3) d 11.85
(s, 1H, OH), 10.14 (s, 1H, NH), 8.41 (t, 1H, J ¼ 1.8 Hz), 8.00–8.10 (m, 4H),
7.7–7.82 (m, 1H), 7.66–7.71 (m, 3H), 7.50 (dd, 1H, J ¼ 2.4, 9.0 Hz), 7.03
(dd, 1H, J ¼ 2.1, 9.0 Hz). MS, m/e (%): 422 (Mþ, 4.59), 423 (Mþ þ 1,
14.69), 421 (Mþ 2 1, 20.70), 311 (12.51), 267 (100), 155 (68.31). Anal.
Calcd for C19H13Cl2NO4S (422.29): C, 54.04; H, 3.10; N, 3.32. Found: C,
54.15; H, 3.26; N, 3.16.
3,5-dichloro-2-hydroxy-N-((4-chloro3-(4-chlorophenylsulfonyl)phenyl)-
benzamide (5q) White solid; mp 278–2808C. IR (KBr) n: 3354, 1664, 1574,
1
1523, 1466, 1430, 1313, 1175 cm21. H NMR (CD3COCD3) d 12.62 (s, 1H,
OH), 10.35 (s, 1H, NH), 8.78 (dd, 1H, J ¼ 1.5, 2.7 Hz), 8.18–8.22 (m, 1H),
8.19 (dd, 1H, J ¼ 1.2, 2.1 Hz), 8.00–8.03 (m, 2H), 7.63–7.74 (m, 4H). MS,
m/e (%): 491 (Mþ, 11.25), 493 (Mþ þ 2, 5.81), 301 (100), 189 (8.27).
HRMS calcd for C19H11Cl4NO4S: 488.9157. Found: 488.9107.
3,5-dichloro-2-hydroxy-N-((4-chloro3-(4-bromophenylsulfonyl)phenyl)-
benzamide (5r) White solid; mp 232–2338C. IR (KBr) n: 3352, 1654, 1576,
1
1523, 1465, 1436, 1309, 1229, 1179 cm21. H NMR (DMSO-d6) d 8.73
(d, 1H, J ¼ 2.1 Hz), 8.10 (dd, 2H, J ¼ 2.1, 8.4 Hz), 7.83 (s, 2H), 7.73 (dd,
2H, J ¼ 2.1, 6.9 Hz), 7.68 (dd, 2H, J ¼ 2.1, 8.1 Hz). MS, m/e (%):535 (Mþ,
12.76), 537 (Mþ þ 2, 8.74), 347 (73.77), 301 (46.35), 189 (100). HRMS
calcd for C19H11BrCl3NO4S: 532.8652. Found: 532.8671.
3,5-dibromo-2-hydroxy-N-((4-chloro3-(4-bromophenylsulfonyl)phenyl)-
benzamide (5s) White solid; mp 284–2858C. IR (KBr) n: 3356, 1653, 1575,
1
1523, 1470, 1440, 1317, 1278, 1149 cm21. H NMR (DMSO-d6) d 8.70
(d, 1H, J ¼ 1.8 Hz), 8.15 (dd, 2H, J ¼ 1.8, 8.7 Hz), 7.76–7.87 (m, 6H). MS,
m/e (%): 625 (Mþ, 8.15), 623 (Mþ 2 2, 6.75), 391 (13.60), 347 (100), 301

Synthetic Study of Substituted Arylsulfonylphenylbenzamides
65
(42.65), 279 (72.57). HRMS calcd for C19H11Br3ClNO4S: 620.764. Found:
620.7601.
ACKNOWLEDGMENT
This project was supported by Chinese Academy of Sciences (KGCX-2-SW-
209)(to Junying Yuan).
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