Amidophenacylating reagents in synthesis of new derivatives of 1,3-oxazole- and 1,3-thiazole-4-sulfonyl chlorides and corresponding sulfonamides

Article abstract of DOI:10.1134/S1070363214040148

Derivatives of 4-benzylsulfanyl-1,3-oxazole and 4-benzylsulfanyl-1,3- thiazole were synthesized using available amidophenacylating reagents. By the oxidative chlorination compounds obtained were converted to 1,3-oxazole-4- sulfonyl and 1,3-thiazol-4-sulfo

Full text of DOI:10.1134/S1070363214040148

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 4, pp. 686–692. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © A.N. Kornienko, S.G. Pil’o, V.M. Prokopenko, V.S. Brovarets, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 4,
pp. 607–613.
Amidophenacylating Reagents in Synthesis of New Derivatives
of 1,3-Oxazole- and 1,3-Thiazole-4-sulfonyl Chlorides
and Corresponding Sulfonamides
A. N. Kornienko, S. G. Pil’o, V. M. Prokopenko, and V. S. Brovarets
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine,
ul. Murmanskaya 1, Kiev, 02660 Ukraine
e-mail: brovarets@bpci.kiev.ua
Received June 17, 2013
Abstract―Derivatives of 4-benzylsulfanyl-1,3-oxazole and 4-benzylsulfanyl-1,3-thiazole were synthesized
using available amidophenacylating reagents. By the oxidative chlorination compounds obtained were converted
to 1,3-oxazole-4-sulfonyl and 1,3-thiazol-4-sulfonyl chlorides. The latter were used to prepare the corresponding
sulfonamides.
Keywords: 1,3-thiazole, 1,3-oxazole, sulfonyl chlorides, sulfonamides
DOI: 10.1134/S1070363214040148
In the past decade, a significant number of natural
and synthetic biologically active compounds
containing 1,3-oxazole or 1,3-thiazole fragments were
prepared [1–5]. It stimulates the studies of reactivity
and search for the ways of heterocycles function-
nalization. In the present work we developed new
methods of the synthesis of 1,3-oxazole- and 1,3-
thiazole-4-sulfonyl chlorides as well as the cor-
responding sulfonamides.
Heating substrates II with the Lawesson’s reagent
in dioxane afforded the thiazole derivatives VIII
(Scheme 2). The latter were converted into 2-aryl-
(methyl)-5-phenyl-1,3-thiazole-4-sulfonyl chlorides IX
by the action of chlorine in acetic acid. Chlorides IX
were used to obtain
a
series of appropriate
sulfonamides X–XII. It should be noted that similar
1,3-thiazole-4-sulfonyl chlorides and 1,3-thiazole-4-
sulfonamides have been known [8–17], however 2,5-
disubstituted 1,3-thiazole-4-sulfonyl chlorides IX and
sulfonamides X–XII we prepared for the first time.
Available amidophenacylating reagents I, which
are convenient syntons for the preparation of a number
of functionally substituted oxazoles and thiazoles [6,
7], were used as starting substrates. 2-Aryl-5-phenyl-4-
benzylsulfanyl-1,3-oxazoles III were obtained through
simple sequence of the reactions I → II → III
(Scheme 1). The oxidative chlorination of these
compounds (Cl2, MeCOOH/H2O, 0°C) afforded 2-
aryl-5-phenyl-1,3-oxazole-4-sulfonyl chlorides IV.
The latter were purified by recrystallization from
aprotic solvents and stored for a long time without any
changes. Treating with excess aqueous ammonia,
primary or secondary amines in the presence of
triethylamine in dioxane resulted in high yields of the
corresponding sulfonamides V–VII. 1,3-Oxazole-4-
sulfonyl chlorides IV and 1,3-oxazole-4-sulfonamides
V–VII were synthesized for the first time.
The composition and structure of new compounds
were confirmed by elemental analysis (Table 1), IR, 1H
and 13C NMR spectra and by LC-MS spectrometry
(Table 2). The formation of azole rings as a result of
transformations II → III and II → VIII was proved
by the disappearance of the signals of >СНNH group
1
in H NMR spectra and intensive absorption bands in
the ranges of 1635–1649 (C=O), 1677–1686 (C=O),
and 3256–3396 cm–1 (N–H) in the IR spectra and by
appearance of the absorption bands at 1143–1384 cm–1
1
belonging to SO2 group. H and 13C NMR spectra of
the synthesized compounds contain all the necessary
signals. In GC-MS spectra there are peaks
corresponding to protonated molecular ions [M + 1]+.
686

AMIDOPHENACYLATING REAGENTS IN SYNTHESIS OF NEW DERIVATIVES
687
Scheme 1.
H
N
H
N
Cl
SBn
Ph
SBn
Ph
N
POCl3
BnSH/Et3N
R
R
Ph
R
Δ
O
O O
Iа−Ic
O O
IIа−IIc
IIIа, IIIb
Cl2/MeCOOH/H2O
SO2Cl
N
R2R3NH/Et3N
NH3 (exess)
R
Δ
Ph
O
IVа, б
Δ
R1NH2/Et3N
SO2NR2R3
Ph
SO2NHR1
SO2NH2
Ph
N
N
N
R
R
R
Ph
VIа−VId
O
O
O
Vа, Vb
VIIа−VIIf
R = Ph (Iа–VIIа, VIc, VIIc, VIIe), 4-MeC6H4 (Ib–VIIb, VId, VIId, VIIf), Me (Ic, IIc); R1NH = PhCH2NH (VIа, VIb),
PhNH (VIc, VId); R2R3N = Me2N (VIIа, VIIb), (CH2)5N (VIIc, VIId), O(CH2)4N (VIIe, VIIf).
Scheme 2.
SO2NH2
N
N
N
NH3 (exess)
R
R
R
IIа−IIc
Ph
Xа−Xc
S
RL
Δ
SO2Cl
SO2NHR1
SBn
Ph
N
N
Cl2/MeCOOH/H2O
R1NH2/Et3N
R
R
Ph
IXа−IXc
Ph
XIа−XIf
Δ
S
S
S
VIIIа−VIIIc
SO2NR2R3
R2R3NH/Et3N
Ph
XIIа−XIIh
Δ
S
R = Ph (IIа, VIIIа–XIIа, XId, XIIc, XIIf), 4-MeC6H4 (IIb, VIIIb–XIIb, XIe, XIId, XIIg), Me (IIc, VIIIc–XIc, XIf,
XIIe, XIIh); R1NH = PhCH2NH (XIа–XIc), PhNH (XId–XIf); R2R3N = Me2N (XIIа, XIIb), (CH2)5N (XIIc–XIIe),
S
P
S
S
OMe.
MeO
O(CH2)4N (XIIf–XIIh); RL =
P
S
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688
KORNIENKO et al.
Table 1. Yields, melting points, and elemental analyses of compounds II–XII
Found, %
Calculated, %
Comp.
no.
mp, °С (solvent for
recrystallization)
Yield, %
Formula
N
S
N
S
IIa
IIb
IIc
IIIa
IIIb
IVa
IVb
Va
85
83
80
70
70
75
72
80
81
86
85
85
84
79
80
84
84
87
87
70
70
65
74
74
67
80
80
72
85
85
80
83
83
80
80
82
85
85
80
86
87
80
122–123 (MеCN)
102–104 (EtOH)
134–135 (EtOH)
89–91 (EtOH)
3.95
3.68
4.55
4.00
3.89
4.21
4.12
9.39
8.93
7.21
6.99
7.41
7.19
8.42
8.11
7.56
7.27
7.58
7.31
3.81
3.55
4.75
4.02
3.35
5.02
8.91
8.52
11.04
6.92
6.70
8.21
7.16
6.84
8.37
8.10
7.75
7.11
7.07
8.57
7.19
7.09
8.60
8.81
8.51
10.73
9.36
8.95
9.94
C22H19NO2S
C23H21NO2S
C17H17NO2S
C22H17NOS
3.87
3.73
4.68
4.08
3.92
4.38
4.20
9.33
8.91
7.17
6.93
7.44
7.17
8.53
8.18
7.60
7.32
7.56
7.29
3.90
3.75
4.71
4.17
4.00
5.12
8.85
8.48
11.01
6.89
6.66
8.13
7.14
6.89
8.48
8.13
7.81
7.29
7.03
8.69
7.25
6.99
8.63
8.87
8.54
10.71
9.34
8.97
10.03
9.61
10.68
10.20
8.21
7.93
8.52
8.21
9.76
9.36
8.70
8.38
8.66
8.34
17.84
17.17
21.56
19.10
18.33
23.42
20.27
19.41
25.21
15.77
15.25
18.62
16.34
15.77
19.41
18.62
17.89
16.68
16.09
19.89
16.59
16.01
19.77
95–96 (EtOH)
C23H19NOS
147–148 (toluene)
102–103 (cyclohexane)
248–249 (MеCN)
254–256 (MеCN)
153–154 (MеCN)
175–176 (MеCN)
204–205 (MеCN)
213–214 (MеCN)
129–130 (EtOH)
126–127 (EtOH)
100–101 (EtOH)
142–143 (EtOH)
119–121 (EtOH)
122–123 (EtOH)
88–89 (MеCN)
105–106 (MеCN)
Oil
131–132 (cyclohexane)
121–122 (cyclohexane)
98–99 (hexane)
236–237 (MеCN)
264–265 (MеCN)
148 (EtOH)
135–136 (MеCN)
158–159 (MеCN)
174–175 (MеCN)
162–163 (MеCN)
171–172 (MеCN)
199–200 (MеCN)
174–175 (MеCN)
209–210 (MеCN)
135–136 (EtOH)
146–147 (MеCN)
131–132 (cyclohexane)
173–174 (MеCN)
132–133 (MеCN)
C15H10ClNO3Sа
C16H12ClNO3Sb
C15H12N2O3S
C16H14N2O3S
C22H18N2O3S
C23H20N2O3S
C21H16N2O3S
C22H18N2O3S
C17H16N2O3S
C18H18N2O3S
C20H20N2O3S
C21H22N2O3S
C19H18N2O4S
C20H20N2O4S
C22H17NS2
9.52
10.65
10.20
8.21
7.91
8.56
8.24
9.79
9.33
8.79
Vb
VIa
VIb
VIc
VId
VIIа
VIIb
VIIc
VIId
VIIe
VIIf
VIIIа
VIIIb
VIIIc
IXa
IXb
IXc
Xa
Xb
Xc
XIa
XIb
XIc
XId
XIe
8.33
8.64
8.31
17.86
17.25
21.52
19.00
18.25
23.38
20.21
19.33
25.21
15.81
15.20
18.57
16.31
15.76
19.44
18.66
17.87
16.72
16.04
19.93
16.59
16.00
19.71
C23H19NS2
C17H15NS2
C15H10ClNO2S2
C16H12ClNO2S2
C10H8ClNO2S2
c
d
e
C15H12N2O2S2
C16H14N2O2S2
C10H10N2O2S2
C22H18N2O2S2
C23H20N2O2S2
C17H16N2O2S2
C21H16N2O2S2
C22H18N2O2S2
C16H14N2O2S2
C17H16N2O2S2
C18H18N2O2S2
C20H20N2O2S2
C21H22N2O2S2
C15H18N2O2S2
C19H18N2O3S2
C20H20N2O3S2
XIf
XIIа
XIIb
XIIc
XIId
XIIe
XIIf
XIIg
XIIh
171–173 (toluene)
C14H16N2O3S2
a
b
c
Found Сl, %: 11.14. Calculated Сl, %: 11.09. Found Сl, %: 10.81. Calculated Сl, %: 10.62. Found Сl, %: 10.72. Calculated Сl, %:
10.56. d Found Сl, %: 10.27. Calculated Сl, %: 10.13. e Found Сl, %: 13.16. Calculated Сl, %: 12.95.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

AMIDOPHENACYLATING REAGENTS IN SYNTHESIS OF NEW DERIVATIVES
Table 2. Spectral data for compounds II–XII
689
Comp.
no.
Mass spectrum,
IR spectrum (KBr), ν, cm–1
1Н NMR spectrum (DMSO-d6)а, δ, ppm
m/z
2
3
IIа
IIb
IIc
1347, 1524; 1635 (С=О), 1686 3.86 d, 4.02 d (2Н, CH2S, JHH 13.0 Hz), 6.65 d (1Н, СН, JHH 362 [M + 1]+
(С=О); 3297 (NН)
3
7.8 Hz), 7.32–7.90 m (15Н, 3С6Н5), 9.25 d (1Н, NH, JHH
7.8 Hz)
1344,1485; 1649 (С=О), 1677 2.38 s (3Н, СН3), 3.86 d, 4.02 d (2Н, CH2S, 2JHH 13.0 Hz), 6.63 376 [M + 1]+
(С=О); 3396 (NН)
d (1Н, СН, 3JHH 7.8 Hz), 7.27–7.87 m (14Н, 2С6Н5, С6Н4), 9.14
d (1Н, NH, 3JHH 7.8 Hz)
1331, 1522; 1647 (С=О), 1684 1.97 s (3Н, СН3), 3.79 d, 3.94 d (2Н, CH2S, 2JHH 13.0 Hz), 6.44 300 [M + 1]+
3
(С=О); 3256 (NН)
d (1Н, СН, JHH 8.0 Hz), 7.28–7.82 m (10Н, 2С6Н5), 8.94 d
(1Н, NH, 3JHH 8.0 Hz)
IIIab 1482, 1552, 1600
4.38 s (2Н, СН2), 7.26–8.13 m (15Н, 3С6Н5)
344 [M + 1]+
IIIb
IVa
IVb
Va
1495, 1556, 1601
2.40 s (3Н, СН3), 4.36 s (2Н, СН2), 7.19–8.01 m (14Н, 2С6Н5, 358 [M + 1]+
С6Н4)
1170, 1384 (SO2); 1487, 1559, 7.28–8.19 m (10Н, 2С6Н5)
–
1606
1170, 1393 (SO2); 1498, 1564, –
–
1611
1157, 1353 (SO2); 1487, 1567; 7.55–8.11 m (12Н, NH2, 2С6Н5)
3206, 3336 (NН2)
301 [M + 1]+
315 [M + 1]+
391 [M + 1]+
Vb
1158, 1352 (SO2); 1496, 1568, 2.41 s (3Н, СН3), 7.42–8.00 m (11Н, NH2, С6Н5, С6Н4)
1612; 3198, 3325 (NН2)
VIa
VIb
VIc
VId
1155, 1336 (SO2); 1448, 1485, 4.27 s (2Н, СН2), 7.23–8.08 m (15Н, 3С6Н5), 8.77 s (1Н, NH)
1547; 3243 (NН)
1151, 1328 (SO2); 1448, 1493, 2.42 s (3Н, СН3), 4.27 s (2Н, СН2), 7.25–7.97 m (14Н, 2С6Н5, 405 [M + 1]+
1555, 1612; 3148 (NН)
С6Н4), 8.72 s (1Н, NH)
1152, 1343 (SO2); 1408, 1485, 7.05–8.04 m (15Н, 3С6Н5), 10.80 s (1Н, NH)
1554; 3269 (NН)
1158, 1339 (SO2); 1413, 1497, 2.39 s (3Н, СН3), 7.05–7.93 m (14Н, 2С6Н5, С6Н4), 10.78 s 391 [M + 1]+
377 [M + 1]+
1556, 1612; 3251 (NН)
(1Н, NH)
VIIаc 1150, 1338 (SO2); 1449, 1488, 2.94 s (6Н, 2СН3), 7.57–8.12 m (10Н, 2С6Н5)
329 [M + 1]+
1556
VIIb 1155, 1347 (SO2); 1449, 1499, 2.41 s (3Н, СН3), 2.93 s (6Н, 2СН3), 7.40–7.99 m (9Н, С6Н5, 343 [M + 1]+
1557, 1612
VIIc 1165, 1336 (SO2); 1447, 1488, 1.48–1.59 m (6Н, 3СН2, piperidine), 3.28–3.33 m (4Н, 2СН2, 369 [M + 1]+
1554 piperidine), 7.57–8.12 m (10Н, 2С6Н5)
VIId 1162, 1351 (SO2); 1442, 1498, 1.47–1.55 m (6Н, 3СН2, piperidine), 2.38 s (3Н, СН3), 3.27– 383 [M + 1]+
1561, 1614 3.37 m (4Н, 2СН2, piperidine), 7.41–8.00 m (9Н, С6Н5, С6Н4)
VIIe 1157, 1344 (SO2); 1448, 1487, 3.30–3.33 m (4Н, 2СН2, morpholine), 3.67–3.70 m (4Н, 2СН2, 371 [M + 1]+
1555 morpholine), 7.57–8.13 m (10Н, 2С6Н5)
1160, 1345 (SO2); 1455, 1497, 2.42 s (3Н, СН3), 3.31–3.34 m (4Н, 2СН2, morpholine), 3.66– 385 [M + 1]+
С6Н4)
VIIf
1556, 1615
3.69 m (4Н, 2СН2, morpholine), 7.41–8.00 m (9Н, С6Н5, С6Н4)
VIIIа 1436, 1451, 1465, 1497, 1595
VIIIbd 1413, 1450, 1468, 1493, 1596
4.49 s (2Н, СН2), 7.21–8.02 m (15Н, 3С6Н5)
360 [M + 1]+
2.39 s (3Н, СН3), 4.49 s (2Н, СН2), 7.29–7.90 m (14Н, 2С6Н5, 374 [M + 1]+
С6Н4)
IXа
1161, 1383 (SO2); 1441, 1464
7.51–8.03 m (10Н, 2С6Н5)
–
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

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KORNIENKO et al.
Table 2. (Contd.)
Comp.
no.
Mass spectrum,
IR spectrum (KBr), ν, cm–1
1Н NMR spectrum (DMSO-d6)а, δ, ppm
m/z
IXb
1157, 1372 (SO2); 1463
–
–
IXc
1168, 1384 (SO2); 1466, 1498
2.81 s (3Н, СН3), 7.48–7.53 m (5Н, С6Н5)
–
Xа
1146, 1334 (SO2); 1439, 1457, 7.49–8.03 m (12Н, NH2, 2С6Н5)
1470; 3222, 3333 (NН2)
317 [M + 1]+
Xb
1151, 1347 (SO2); 1455, 1472, 2.37 s (3Н, СН3), 7.38–7.92 m (11Н, NH2, С6Н5, С6Н4)
1566; 3192, 3350 (NН2)
331 [M + 1]+
255 [M + 1]+
407 [M + 1]+
421 [M + 1]+
345 [M + 1]+
393 [M + 1]+
407 [M + 1]+
331 [M + 1]+
Xc
1149, 1346 (SO2); 1442, 1469, 2.71 s (3Н, СН3), 7.43–7.55 m (7Н, NH2, С6Н5)
1492, 1555; 3282, 3346 (NН2)
XIа
XIb
XIc
XId
XIe
XIf
1145, 1325 (SO2); 1427, 1455, 4.29 s (2Н, СН2), 7.25–7.98 m (15Н, 3С6Н5), 8.62 s (1Н,
1469; 3294 (NН)
1143, 1340 (SO2); 1408, 1454, 2.41 s (3Н, СН3), 4.29 s (2Н, СН2), 7.21–7.87 m (14Н,
1470; 3308 (NН) 2С6Н5, С6Н4), 8.58 s (1Н, NH)
1145, 1338 (SO2); 1420, 1443, 2.67 s (3Н, СН3), 4.16 s (2Н, СН2), 7.22–7.52 m (10Н,
1499; 3290 (NН) 2С6Н5), 8.47 s (1Н, NH)
NH)
1148, 1349 (SO2); 1408, 1474, 7.15–7.92 m (15Н, 3С6Н5), 10.65 s (1Н, NH)
1502, 1598; 3241 (NН)
1149, 1348 (SO2); 1412, 1457, 2.38 s (3Н, СН3), 7.16–7.80 m (14Н, 2С6Н5, С6Н4), 10.62 s
1473, 1494, 1597; 3241 (NН)
(1Н, NH)
1155, 1356 (SO2); 1426, 1487, 2.67 s (3Н, СН3), 7.03–7.46 m (10Н, 2С6Н5), 10.49 s (1Н,
1595; 3127 (NН)
NH)
XIIа
XIIbe
1145, 1352 (SO2); 1440, 1459
1145, 1352 (SO2); 1460
2.95 s (6Н, 2СН3), 7.51–8.07 m (10Н, 2С6Н5)
2.41 s (3Н, СН3), 2.92 s (6Н, 2СН3), 7.38–7.89 m (9Н,
С6Н5, С6Н4)
345 [M + 1]+
359 [M + 1]+
XIIc
XIId
1166, 1334 (SO2); 1440, 1455, 1.50–1.58 m (6Н, 3СН2, piperidine), 3.30–3.34 m (4Н,
385 [M + 1]+
399 [M + 1]+
1470
2СН2, piperidine), 7.51–8.00 m (10Н, 2С6Н5)
1.52–1.57 m (6Н, 3СН2, piperidine), 2.40 s (3Н, СН3),
3.29–3.33 m (4Н, 2СН2, piperidine), 7.40–7.89 m (9Н,
С6Н5, С6Н4)
1158, 1343 (SO2); 1473
XIIe
XIIf
XIIg
1146, 1344 (SO2); 1442, 1470, 1.47–1.53 m (6Н, 3СН2, piperidine), 2.72 s (3Н, СН3),
323 [M + 1]+
387 [M + 1]+
401 [M + 1]+
1500
3.17–3.33 m (4Н, 2СН2, piperidine), 7.46–7.50 m (5Н, С6Н5)
3.27–3.31 m (4Н, 2СН2, morpholine), 3.65–3.68 m (4Н,
2СН2, morpholine), 7.52–8.01 m (10Н, 2С6Н5)
2.40 s (3Н, СН3), 3.30–3.34 m (4Н, 2СН2, morpholine),
3.67–3.70 m (4Н, 2СН2, morpholine), 7.38–7.89 m (9Н,
С6Н5, С6Н4)
1157, 1356 (SO2); 1442, 1458
1158, 1356 (SO2); 1452
XIIh
1157, 1350 (SO2); 1451, 1499
2.74 s (3Н, СН3), 3.18–3.22 m (4Н, 2СН2, morpholine),
3.60–3.64 m (4Н, 2СН2, morpholine), 7.46–7.51 m (5Н,
С6Н5)
325 [M + 1]+
a
1Н NMR spectra of IVа, IXа, IXc were recorded in CDCl3. b 13С NMR spectrum (DMSО-d6), δC, ppm: 37.59 (SСН2), 125.61, 126.65,
c
126.68, 127.63, 127.69, 128.85, 128.92, 129.33, 129.70, 130.41, 131.54, 138.21, 147.89 (C4, oxazoline), 159.76 (C2, oxazoline). 13С
NMR spectrum (DMSО-d6), δC, ppm: 38.46 [N(СН3)2], 126.00, 126.15, 127.06, 128.97, 129.12, 129.78, 131.06, 132.19, 134.34 (C4,
d
oxazoline), 151.95, 159.71 (C2, oxazoline). 13С NMR spectrum (DMSО-d6), δC, ppm: 21.51 (CH3), 37.86 (SСН2), 126.39, 127.55,
e
128.72, 128.83, 128.99, 129.33, 130.36, 130.42, 130.95, 131.67, 138.65, 141.13, 144.14 (C4, oxazoline), 165.26 (C2, oxazoline). 13С
NMR spectrum (DMSО-d6), δC, ppm: 21.54 (CH3), 38.65 [N(СН3)2], 126.66, 128.89, 129.57, 130.10, 130.53, 141.94, 142.06, 146.62,
155.41 (C4, oxazoline), 166.35 (C2, oxazoline).
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AMIDOPHENACYLATING REAGENTS IN SYNTHESIS OF NEW DERIVATIVES
691
Some 1,3-thiazole-4-sulfonamides were screened
for anticancer activity within the International
Scientific Program of the National Cancer Institute
(USA) [18–21]. The screening was performed in vitro
at 60 cancer cell lines under the action of the substance
in a concentration of 1×10–5 M, whereby the cancer
cells growth index (GI) was determined in comparison
with reference (100%). Among the investigated
compounds, sulfonamide XIb showed moderate
activity as inhibitor of the growth of leukemia cell
lines (K-562, GI = 43.77%; MOLT-4, GI = 44.21%),
prostate cancer (PS-3, GI = 40.44%), breast cancer
(T-47D, GI = 42.51%); sulfonamide XId showed
moderate activity as inhibitor of the growth of
leukemia cell lines (RPMI, GI = 48.16%), lung cancer
(A549/ATCC, GI = 48.18%), intestines cancer (HCT-
116, GI = 31.46%), breast cancer (T-47D, GI =
46.42%) and a significant activity against renal cancer
lines (UO-31 , GI = –56.83%).
precipitate was filtered off, dried, and purified by
recrystallization.
2-Aryl-4-benzylsulfanyl-5-phenyl-1,3-oxazoles
(IIIa, IIIb). A solution of 0.025 mol of compound IIa
or IIb in 30 mL of POCl3 was refluxed for 5 h, then
maintained at 20–25°C for 12 h and poured into ice.
The formed precipitate was filtered off, dried, and
purified by recrystallization.
2-Aryl-5-phenyl-1,3-oxazole-4-sulfonyl chlorides
(IVa, IVb). To a solution of 0.01 mol of compound
IIIa or IIIb in 30 mL of 95% acetic acid was bubbled
at stirring Cl2 for 0.5 h maintaining the reaction
temperature in the range of 0–5°C. Then the mixture
was maintained at this temperature for 12 h and poured
into ice. The formed precipitate was filtered off, dried
in a vacuum desiccator over phosphorus pentoxide and
purified by recrystallization.
2-Aryl-5-phenyl-1,3-oxazole-4-sulfonamides (Va,
Vb). To a solution (50 mL) of 25% aqueous ammonia
while stirring and cooling with ice water was added
dropwise a solution of 0.005 mol of compound IVa or
VIb in 15 mL of anhydrous dioxane. The slurry was
stirred at 20–25°C for 0.5 h. The formed precipitate
was filtered off, dried, and purified by recrystallization.
In summary, starting from available amido-
phenacylating reagents we have developed new
methods for the synthesis of 1,3-oxazole- and 1,3-
thiazole-4-sulfonyl chlorides and sulfonamides, which
are potential bioactive compounds.
EXPERIMENTAL
2-Aryl-N-benzyl(phenyl)-5-phenyl-1,3-oxazole-4-
sulfonamides (VIa–VId). To a solution of 0.005 mol
of sulfonyl chloride IVa or IVb in 15 mL of an-
hydrous dioxane was added 0.005 mol of the appro-
priate amine (benzylamine or aniline) and 0.005 mol of
Et3N. The mixture was refluxed for 2 h, and then
maintained at 20–25°C for 12 h. The solvent was
removed in a vacuum, and the residue was treated with
water. The formed precipitate was filtered off, dried,
and purified by recrystallization.
IR spectra were recorded on a Vertex 70 instrument
1
from KBr pellets. H and 13С NMR spectra were
obtained on
a
Bruker AVANCE DRX-500
spectrometer operating at 500 and 125 MHz,
respectively, internal reference TMS. LC-MS spectra
were registered on an Agilent 1100 Series HPLC
chromatograph equipped with a diode array with a
mass selective detector Agilent LC\MSD SL. GC-MS
analysis parametersare as follows: column Zorbax SB-
C18, 1.18 μm, 4.6 × 15 mm (PN 821975-932); aceto-
nitrile–water (95 : 5), 0.1% aqueous trifluoroacetic
acid, flow rate of the eluent 3 mL min–1, injection
volume 1 μL; UV detecting at 215, 254, 285 nm;
chemical ionization at atmospheric pressure (APCI),
scan range m/z 80–1000. Melting points were
measured on a Fisher-Johns instrument.
2-Aryl-N,N-dimethyl-5-phenyl-1,3-oxazole-4-sulfon-
amides (VIIa, VIIb). To 50 mL of 40% aqueous
dimethylamine with stirring and cooling with ice water
was added a solution of 0.005 mol of compound IVa
or IVb in 15 mL of anhydrous dioxane. The slurry was
stirred at 20–25°C for 0.5 h, and the formed precipitate
was filtered off, dried and purified by recrystallization.
2-Aryl-N,N-R1R2-5-phenyl-1,3-oxazole-4-sulfon-
amides (VIIc-–VIIf) were prepared similarly to
compounds VIa–VId from IVa or IVb and mor-
pholine or piperidine.
Carboxylic acids N-(1-benzylsulfanyl-2-oxo-2-
phenylethyl)amides (IIa–IIc). To a solution of
0.05 mol of compound Ia–Ic [6, 22] in 200 mL of
anhydrous acetonitrile were added benzylthiol
(0.05 mol) and Et3N (0.05 mol). The mixture was
refluxed and then maintained at 20–25°C for 12 h. To
the solution was added 400 mL of water. The
2-Aryl(methyl)-4-benzylsulfanyl-5-phenyl-1,3-
thiazoles (VIIIa–VIIIc). A mixture of 0.025 mol of
compound IIa–IIc and 0.025 mol of the Lawesson’s
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

692
KORNIENKO et al.
6. Belyuga, A.G., Brovarets, V.S., and Drach, B.S., Russ.
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reagent in 120 mL of anhydrous dioxane was refluxed
for 8 h, and then maintained at 20–25°C for 12 h. The
solvent was removed in a vacuum. The residue was
treated with 5% aqueous sodium hydroxide solution.
The precipitate was filtered off and dried. Compounds
VIIIa, VIIIb were purified by recrystallization.
Compound VIIIc was extracted with chloroform, the
extract was dried over anhydrous magnesium sulfate
and concentrated in a vacuum to afford VIIIc which
was used in the next steps without further purification.
2-Aryl(methyl)-5-phenyl-1,3-thiazole-4-sulfonyl
chlorides (IXa–IXc) were prepared similarly to
compounds IVa, IVb from corresponding thiazoles
VIIIa–VIIIc.
2-Aryl(methyl)-5-phenyl-1,3-thiazole-4-sulfonamides
(Xa–Xc) were prepared similarly to compounds Va,
Vb from corresponding sulfonyl chlorides IXa–IXc
and aqueous ammonia solution.
2-Aryl(methyl)-N-benzyl(phenyl)-5-phenyl-1,3-
thiazole-4-sulfonamides (XIa–XIf) were prepared
similarly to compounds VIa–VId from corresponding
sulfonyl chlorides IXa–IXc and benzylamine or aniline.
12. Harry, R. and Howard, J., USA Patent US5703065,
1997.
2-Aryl-N,N-dimethyl-5-phenyl-1,3-thiazole-4-
sulfonamides (XIIa, XIIb) were prepared similarly to
compounds VIIa, VIIb from corresponding sulfonyl
chlorides IXa, IXb and dimethylamine aqueous solution.
2-Aryl(methyl)-N,N-R1R2-5-phenyl-1,3-thiazole-
4-sulfonamides (XIIc–XIIh) were prepared similarly
to compounds VIa–VId from corresponding sulfonyl
chlorides IXa–IXc and piperidine or morpholine.
13. Campbell, J.A. and Good, A.C., WO Patent
2003/099316, 2003.
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