Synthesis of 5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-2,3-dihydro-1H-pyrrol-3-ones

Article abstract of DOI:10.1023/A:1013196008180

Reactions of 2-(4-aryl-1,3-thiazol-2-yl)-3-oxo-4-chlorobutyronitriles with primary aromatic amines result in nucleophilic substitution of the chlorine atom by amino group, followed by intramolecular addition of the secondary amino group to the cyano group

Full text of DOI:10.1023/A:1013196008180

Russian Journal of Organic Chemistry, Vol. 37, No. 9, 2001, pp. 1323 1329. Translated from Zhurnal Organicheskoi Khimii, Vol. 37, No. 9, 2001,
pp. 1389 1394.
Original Russian Text Copyright
2001 by Volovenko, Volovnenko, Tverdokhlebov, Ryabokon’.
Synthesis of 5-Amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-
2,3-dihydro-1H-pyrrol-3-ones*
Yu. M. Volovenko1, T. A. Volovnenko1, A. V. Tverdokhlebov1, and I. G. Ryabokon’2
1
Taras Shevchenko Kiev National University, ul. Vladimirskaya 62, Kiev, 01033 Ukraine
e-mail: atver@mail.univ.kiev.ua
2
Ukrainian State University of Food Technologies, Kiev, Ukraine
Received May 5, 2000
Abstract Reactions of 2-(4-aryl-1,3-thiazol-2-yl)-3-oxo-4-chlorobutyronitriles with primary aromatic amines
result in nucleophilic substitution of the chlorine atom by amino group, followed by intramolecular addition
of the secondary amino group to the cyano group. The products are 5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-
2,3-dihydro-1H-pyrrol-3-ones which are structurally related to the known antiischemic drugs.
In the recent years, a number of compounds pos-
sessing high biological activity of various kinds
were found among heteryl-substituted pyrroles. For
example, pyridyl derivatives Ia and Ib (Scheme 1)
inhibit biosynthesis of cholesterol, and they can be
used for prevention and treatment of atherosclerosis
[1]; benzoxazolyl-substituted pyrrole II exhibits
antihelmintic properties [2], and tetrazolyl derivatives
IIIa IIId show antihypertensive activity [3]. Imid-
azolyl and thiazolyl derivatives IVa IVc inhibit
thrombosis and were recommended as antiischemic
remedies [4]. In particular, compound IVc is by
a factor of 3500 more potent than aspirin (as test com-
pound) in vitro and 200 times more potent ex vivo [4].
Scheme 1.
I, R = 2-pyridyl (a), 4-pyridyl (b); III, R = R = H (a); R = H, R = Cl (b); R = CF3, R = H (c); R = F, R = H (d); IV, X = NH,
R = H (a); X = S, R = H (b); X = S, R = CH3 (c).
____________
*
This study was financially supported by DuPont de Nemours.
1070-4280/01/3709-1323$25.00 2001 MAIK Nauka/Interperiodica

1324
VOLOVENKO et al.
Scheme 2.
V, VIII, XI, R = H; VI, IX, XII, R = Cl; VII, X, XIII, R = Br; Ar = Ph (a), 2-MeC6H4 (b), 3-MeC6H4 (c), 4-MeC6H4 (d),
2-MeOC6H4 (e), 3-MeOC6H4 (f), 4-MeOC6H4 (g), 2,4-F2C6H3 (h), 2-FC6H4 (i), 4-i-PrC6H4 (j), 2-F3COC6H4 (k), 3-F3CC6H4 (l),
4-piperidinophenyl (m), 4-PhOC6H4 (n), 4-EtOCOCH2C6H4 (o), 3,4-(CH2O)2C6H3 (p), 1-C10H7 (q), 2-C10H7 (r), 4-morpholino-
phenyl (s), 2,3-dihydro-1,4-benzodioxin-6-yl (t), 4-Me2NC6H4 (u), 4-ClC6H4 (v), 4-HOCOC6H4 (w), 4-Cl-2-MeC6H3 (x).
Taking the above into account, increasing interest
in heteryl-substituted pyrroles becomes clearly under-
stood. 2-Hetarylpyrroles were studied in sufficient
detail, while the information on their 3-substituted
analogs is much more scanty. The reason lies in dif-
ferent strategies of the synthesis of 2- and 3-hetaryl
derivatives. 2-Hetarylpyrroles are usually obtained
from readily accessible functionally substituted pyr-
roles, and heterocyclic fragment is built up on the
basis of functional substituent in position 2 [2 4].
By contrast, 3-hetarylpyrroles are synthesized by
building up pyrrole ring from acyclic precursor having
a heterocyclic moiety in the desired position [1]. Such
precursors are much more difficultly accessible than
2-functionalized pyrroles.
by us previously [10] via C-acylation of accessible
4-arylthiazol-2-ylacetonitriles VIII X [11 13] with
chloroacetyl chloride in the presence of pyridine
(Scheme 2). Halogen-substituted nitriles V VII were
found to react with aromatic amines, affording
5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-2,3-di-
hydro-1H-pyrrol-3-ones XIb XId, XIh XIj, XIm
XIo, XIIa XIIh, XIIj, XIIk, XIIm XIIp, XIIr,
XIIs, XIIIa XIIIf, and XIIIk XIIIx. The reaction
scheme includes alkylation of aromatic amine with
formation of intermediate A which undergoes hetero-
cyclization via intramolecular addition of the secon-
dary amino group to cyano group. Analogs of inter-
mediates A were reported in [9].
The structure of thiazolylpyrroles XI XIII was
For many years, synthesis of 3-hetarylpyrroles was confirmed by spectral data and elemental analyses.
the subject for study in our laboratory: we have syn-
thesized pyrrole derivatives containing pyridyl [5, 6],
benzimidazolyl [5 9], and benzothiazolyl groups
[8, 9] in position 3. The present work continues the
research in this line; it was aimed at synthesizing
3-(2-thiazolyl)-substituted pyrroles since just thiazolyl
derivatives IV exhibit the strongest biological activity
among the known pyrrole compounds.
The target compounds were synthesized following
the above strategy according to which the pyrrole ring
was built up on the basis of acyclic precursors. The
required starting compounds, 2-(4-arylthiazol-2-yl)-
3-oxo-4-chlorobutyronitriles V VII were obtained
The IR spectra of XI XIII lack absorption in the
region 2180 2200 cm , which is typical of initial
1
halonitriles V VII [10]. Instead, two absorption bands
1
appear at 3300 3340 and 3100 3150 cm due to
stretching vibrations of the primary amino group. It
should be emphasized that we observed no carbonyl
absorption in the IR spectra of compounds XI XIII.
This is typical of -enaminoketone fragment and is
consistent with the known data [7 9, 14] for 5-amino-
2,3-dihydropyrrol-3-ones.
1
The H NMR spectra of thiazolyl derivatives XI
XIII, recorded in DMSO-d6, contain a two-proton
singlet from the methylene group at 4.1 4.5 ppm
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

SYNTHESIS OF 5-AMINO-1-ARYL-4-(4-ARYL-1,3-THIAZOL-2-YL)-. . .
1325
Table 1. Yields, melting points, and elemental analyses of 5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-2,3-dihydropyrrol-
3-ones XIb XId, XIh XIj, XIm XIo, XIIa XIIh, XIIj, XIIk, XIIm XIIp, XIIr, XIIs, XIIIa XIIIf, and XIIIk XIIx
Found, %
Calculated, %
Comp.
no.
Yield, %
mp,
C
Formula
N
S
N
S
XIb
XIc
XId
XIh
XIi
XIj
XIm
XIn
XIo
52
59
64
56
54
50
61
58
49
65
62
68
64
60
59
64
57
49
61
69
59
59
64
60
64
50
56
58
51
62
53
61
64
53
54
59
48
57
50
46
59
51
59
42
48
268
208
291
219
221
273
310
257
198
294
307
252
302
294
234
303
>300
284
>300
>300
298
227
282
>300
>300
296
>300
249
298
288
239
>300
>300
>300
294
241
296
12.00
12.12
12.20
11.29
12.06
11.05
13.39
9.94
9.18
9.09
9.31
8.61
9.00
8.69
7.84
7.62
7.45
8.84
8.46
8.42
8.35
8.14
8.20
8.12
8.10
8.74
6.95
7.19
7.00
6.97
7.84
7.58
6.99
7.71
7.46
7.41
7.39
7.19
7.33
6.42
6.74
6.44
6.47
6.32
6.89
7.04
6.99
6.41
6.78
6.98
7.16
7.06
6.89
C20H17N3OS
C20H17N3OS
C20H17N3OS
C19H13F2N3OS
C19H14FN3OS
C22H21N3OS
C24H24N4OS
C25H19N3O2S
12.09
12.09
12.09
11.38
11.96
11.19
13.45
9.88
10.02
11.42
11.00
11.00
11.00
10.56
10.56
10.56
10.41
10.25
9.30
12.42
9.14
9.26
10.20
10.05
12.37
10.19
9.86
9.86
9.86
9.50
9.50
8.47
8.75
11.31
8.33
8.43
9.21
9.09
9.09
11.26
8.93
12.30
9.41
9.21
9.23
9.23
9.23
8.68
9.12
8.54
7.70
7.54
7.64
8.72
8.40
8.40
8.40
8.06
8.06
8.06
7.94
7.82
7.10
7.11
6.97
7.06
7.78
7.67
7.08
7.78
7.52
7.52
7.52
7.25
7.25
6.46
6.68
6.47
6.36
6.43
7.03
6.93
6.93
6.45
6.82
7.04
7.18
7.03
6.96
9.98
C23H21N3O3S
XIIa
XIIb
XIIc
XIId
XIIe
XIIf
XIIg
XIIh
XIIj
XIIk
XIIm
XIIn
XIIo
XIIp
XIIr
XIIs
XIIIa
XIIIb
XIIIc
XIIId
XIIIe
XIIIf
XIIIk
XIIIl
XIIIm
XIIIn
XIIIo
XIIIp
XIIIq
XIIIr
XIIIs
XIIIt
XIIIu
XIIIv
XIIIw
XIIIx
11.36
10.89
11.14
10.94
10.42
10.59
10.61
10.35
10.26
9.13
12.39
9.03
9.37
10.08
9.96
12.26
10.08
9.76
9.94
10.01
9.53
9.54
8.32
8.77
11.50
8.21
8.39
9.04
C19H14ClN3OS
C20H16ClN3OS
C2OH16ClN3OS
C20H16ClN3OS
C20H16ClN3O2S
C20H16ClN3O2S
C20H16ClN3O2S
C19H12ClF2N3OS
C22H20ClN3OS
C20H13ClF3N3O2S
C24H23ClN4OS
C25H18ClN3O2S
C23H20ClN3O3S
C20H14ClN3O3S
C23H16ClN3OS
C23H21ClN4O2S
C19H14BrN3OS
C20H16BrN3OS
C20H16BrN3OS
C20H16BrN3OS
C20H16BrN3O2S
C20H16BrN3O2S
C20H13BrF3N3O2S
C20H13BrF3N3OS
C24H23BrN4OS
C25H18BrN3O2S
C23H20BrN3O3S
C20H14BrN3O3S
C23H16BrN3OS
C23H16BrN3OS
C23H21BrN4O2S
C21H16BrN3O3S
C21H19BrN4OS
C19H13BrClN3OS
C20H14BrN3O3S
C20H15BrClN3OS
>300
>300
>300
>300
>300
227
9.11
8.94
11.14
8.99
12.27
9.46
>300
291
9.17
9.09
9.12
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

1326
VOLOVENKO et al.
Table 2. 1H NMR spectra of 5-amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-2,3-dihydropyrrol-3-ones XIb XId, XIh XIj,
XIm XIo, XIIa XIIh, XIIj, XIIk, XIIm XIIp, XIIr, XIIs, XIIIa XIIIf, and XIIIk XIIxa
Comp.
no.
Chemical shifts , ppm
XIb
XIc
XId
2.26 s (3H, CH3), 4.16 s (2H, CH2), 7.39 m (7H, 3-H, 4-H, 5-H, Harom), 7.67 s (1H, SCH), 7.92 d.d (2H, 2-H,
6-H, J = 7.0, 1.0 Hz), 8.30 br.s (2H, NH2)
2.36 s (3H, CH3), 4.31 s (2H, CH2), 7.36 m (7H, 3-H, 4-H, 5-H, Harom), 7.70 s (1H, SCH), 7.93 d.d (2H, 2-H,
6-H, J = 7.5, 1.5 Hz), 8.20 br.s (2H, NH2)
2.36 s (3H, CH3), 4.25 s (2H, CH2), 7.40 m (7H, 3-H, 4-H, 5-H, Harom), 7.65 s (1H, SCH), 7.92 d.d (2H, 2-H,
6-H, J = 8.0, 2.0 Hz), 8.20 br.s (2H, NH2)
XIh
XIi
4.47 s (2H, CH2), 7.48 7.51 m (6H, 3-H, 4-H, 5-H, Harom), 7.75 m (5H, NH2, 2-H, 6-H, SCH)
4.48 s (2H, CH2), 6.80 br.s (2H, NH2), 7.50 m (8H, 3-H, 4-H, 5-H, SCH, Harom), 7.78 d.d (2H, 2-H, 6-H, J =
7.0, 2.0 Hz)
XIj
1.23 d (6H, CH3, J = 10.0 Hz), 2.96 m (1H, HC), 4.25 s (2H, CH2), 7.41 m (7H, 3-H, 4-H, 5-H, Harom), 7.63 s
(1H, SCH), 7.91 d.d (2H, 2-H, 6-H, J = 7.5, 1.5 Hz), 8.25 br.s (2H, NH2)
XIm
1.61 m (6H, CH2CH2CH2), 3.17 t (4H, CH2NCH2, J = 6.0 Hz), 4.17 s (2H, CH2), 7.00 d (2H, 3-H, 5-H, J =
9.0 Hz), 7.36 m (5H, 3-H, 4-H, 5-H, 2-H, 6-H, J = 9.0 Hz), 7.64 s (1H, SCH), 7.90 d.d (2H, 2-H, 6-H, J =
8.0, 1.5 Hz), 8.06 br.s (2H, NH2)
XIn
XIo
4.29 s (2H, CH2), 7.11 m (5H, OPh), 7.41 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.48 m (3H, 3-H, 4-H, 5-H), 7.51 d
(2H, 2-H, 6-H, J = 9.0 Hz), 7.70 s (1H, SCH), 7.92 d.d (2H, 2-H, 6-H, J = 8.0, 1.5 Hz), 8.32 br.s (2H, NH2)
1.21 t (3H, CH3, J = 11.0 Hz), 3.72 s (2H, ArCH2CO2Et), 4.09 q (2H, OCH2, J = 11.0 Hz), 4.31 s (2H,
NCH2CO), 7.43 m (7H, 3-H, 4-H, 5-H, Harom), 7.70 s (1H, SCH), 7.93 d.d (2H, 2-H, 6-H, J = 7.0, 1.0 Hz),
8.40 br.s (2H, NH2)
XIIa
XIIb
XIIc
XIId
XIIe
4.33 s (2H, CH2), 7.53 m (5H, Harom), 7.69 s (1H, SCH), 7.71 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.92 d (2H, 2-H,
6-H, J = 9.0 Hz), 8.29 s (2H, NH2)
2.26 s (3H, CH3), 4.14 s (2H, CH2), 7.39 s (4H, Harom), 7.60 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.73 s (1H, SCH),
7.90 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.30 s (2H, NH2)
2.37 s (3H, CH3), 4.29 s (2H, CH2), 7.11 7.41 m (4H, Harom), 7.62 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.76 s (1H,
SCH), 7.91 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.30 s (2H, NH2)
2.36 s (3H, CH3), 4.25 s (2H, CH2), 7.34 s (4H, Harom), 7.60 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.72 s (1H, SCH),
7.89 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.15 s (2H, NH2)
3.84 s (3H, OCH3), 4.12 s (2H, CH2), 7.08 t.d (1H, 5-Harom, J = 7.0, 1.5 Hz), 7.22 d (1H, 3-Harom, J =
7.0 Hz), 7.45 m (2H, 4-H, 6-H, J = 7.0, 1.5 Hz), 7.61 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.77 s (1H, SCH),
7.90 d (2H, 2-H, 6-H, J = 8.5 Hz), 8.30 s (1H, HN), 9.00 s (1H, NH N)
XIIf
3.84 s (3H, OCH3), 4.33 s (2H, CH2), 6.97 m (2H, 4-H, 6-H), 7.10 d (1H, 2-H, J = 1.5 Hz), 7.44 t (1H, 5-H,
J = 8.5 Hz), 7.63 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.76 s (1H, SCH), 7.92 d (2H, 2-H, 6-H, J = 8.5 Hz), 8.33 s
(2H, NH2)
XIIg
XIIh
XIIj
XIIk
3.81 s (3H, OCH3), 4.21 s (2H, CH2), 7.05 d (2H, 3-H, 5-H, J = 9.5 Hz), 7.41 d (2H, 2-H, 6-H, J = 9.5 Hz),
7.60 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.70 s (1H, SCH), 7.88 d (2H, 2-H, 6-H, J = 8.5 Hz), 8.10 s (2H, NH2)
4.20 s (2H, CH2), 7.20 7.52 m (3H, Harom), 7.62 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.78 s (1H, SCH), 7.94 d (2H,
2-H, 6-H, J = 8.5 Hz), 8.30 s (2H, NH2)
1.25 d (6H, CH3, J = 10.0 Hz), 2.95 m (1H, HC), 4.30 s (2H, CH2), 7.40 s (4H, Harom), 7.63 d (2H, 3-H, 5-H,
J = 9.0 Hz), 7.77 s (1H, SCH), 7.91 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.27 s (2H, NH2)
4.35 s (2H, CH2), 7.61 m (6H, 3-H, 5-H, Harom), 7.76 s (1H, SCH), 7.93 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.43 s
(2H, NH2)
XIIm 1.61 m (6H, CH2CH2CH2), 3.18 t (4H, CH2NCH2, J = 6.0 Hz), 4.17 s (2H, CH2), 7.00 d (2H, 3-H, 5-H, J =
9.5 Hz), 7.30 d (2H, 2-H, 6-H, J = 9.5 Hz), 7.61 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H, SCH), 7.89 d
(2H, 2-H, 6-H, J = 9.0 Hz), 7.98 s (1H, NH2)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

SYNTHESIS OF 5-AMINO-1-ARYL-4-(4-ARYL-1,3-THIAZOL-2-YL)-. . .
Chemical shifts , ppm
1327
Table 2. (Contd.)
Comp.
no.
XIIn
4.26 s (2H, CH2), 7.02 7.24 m (5H, OPh), 7.41 d (2H, 3-H, 5-H, J = 9.5 Hz), 7.50 d (2H, 2-H, 6-H, J =
9.5 Hz), 7.60 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.72 s (1H, SCH), 7.89 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.20 s
(2H, NH2)
XIIo
1.21 t (3H, CH3, J = 11.0 Hz), 3.71 s (2H, ArCH2CO2Et), 4.17 q (2H, OCH2, J = 11.0 Hz), 4.28 s (2H,
NCH2CO), 7.42 s (4H, Harom), 7.61 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.72 s (1H, SCH), 7.90 d (2H, 2-H, 6-H,
J = 8.5 Hz), 8.30 s (2H, NH2)
XIIp
XIIr
XIIs
4.21 s (2H, CH2), 6.09 s (2H, OCH2O), 6.99 m (2H, 5-H, 6-H), 7.12 d (1H, 2-H, J = 1.5 Hz), 7.62 d (2H,
3-H, 5-H, J = 9.0 Hz), 7.73 s (1H, SCH), 7.90 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.15 s (2H, NH2)
4.39 s (2H, CH2), 7.41 7.64 m (6H, 3-H, 5-H; SCH; 3-H, 6-H, 7-Harom), 7.88 8.10 m (6H, 2-H, 6-H; 1-H,
4-H, 5-H, 8-Harom), 8.45 s (2H, NH2)
3.33 t (4H, CH2NCH2, J = 7.0 Hz), 3.75 t (4H, CH2OCH2, J = 7.0 Hz), 4.19 s (2H, CH2), 7.05 d (2H, 3-H,
5-H, J = 9.5 Hz), 7.34 d (2H, 2-H, 6-H, J = 9.5 Hz), 7.61 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H, SCH),
7.88 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.20 s (1H, NH), 8.91 s (1H, NH N)
XIIIa 4.30 s (2H, CH2), 7.48 m (7H, 3-H, 5-H, Harom), 7.70 s (1H, SCH), 7.94 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.26 s
(2H, NH2)
XIIIb 2.26 s (3H, CH3), 4.13 s (2H, CH2), 7.39 s (4H, Harom), 7.47 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H, SCH),
7.93 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.30 s (2H, NH2)
XIIIc 2.37 s (3H, CH3), 4.30 s (2H, CH2), 7.20 m (3H, 4-H, 5-H, 6-Harom), 7.33 s (2H, 2-Harom), 7.50 d (2H, 3-H,
5-H, J = 9.0 Hz), 7.75 s (1H, SCH), 7.98 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.31 s (2H, NH2)
XIIId 2.35 s (3H, CH3), 4.25 s (2H, CH2), 7.35 s (4H, Harom), 7.48 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.71 s (1H, SCH),
7.95 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.17 s (2H, NH2)
XIIIe 3.84 s (3H, OCH3), 4.10 s (2H, CH2), 7.07 t.d (1H, 5-Harom, J = 7.0, 1.5 Hz), 7.20 d.d (1H, 3-Harom, J = 7.0,
1.5 Hz), 7.40 d.d (1H, 6-Harom, J = 7.0, 1.5 Hz ), 7.43 t.d (1H, 4-Harom, J = 7.0, 1.5 Hz ), 7.48 d (2H, 3-H,
5-H, J = 8.5 Hz), 7.70 s (1H, SCH), 7.94 d (2H, 2-H, 6-H, J = 8.5 Hz), 8.30 s (1H, NH), 9.00 s (1H,
NH N)
XIIIf
3.82 s (3H, OCH3), 4.33 s (2H, CH2), 6.96 m (2H, 4-H, 5-Harom), 7.10 d (1H, 2-Harom, J = 1.0 Hz), 7.49 d
(1H, 6-Harom, J = 9.0 Hz), 7.50 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.78 s (1H, SCH), 7.98 d (2H, 2-H, 6-H, J =
9.0 Hz), 8.40 s (2H, NH2)
XIIIk 4.31 s (2H, CH2), 7.52 m (6H, 3-H, 5-H, Harom), 7.73 s (1H, SCH), 7.97 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.38 s
(2H, NH2)
XIIIl
4.39 s (2H, CH2), 7.50 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.72 m (3H, 4-H, 5-H, 6-Harom), 7.80 s (1H, SCH),
7.88 s (1H, 2-Harom), 8.00 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.52 s (2H, NH2)
XIIIm
1.60 m (6H, CH2CH2CH2), 3.20 t (4H, CH2NCH2, J = 5.0 Hz), 4.18 s (2H, CH2), 7.01 d (2H, 3-H, 5-H, J =
9.5 Hz), 7.30 d (2H, 2-H, 6-Harom, J = 9.5 Hz), 7.48 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H, SCH), 7.94 d
(2H, 2-H, 6-H, J = 9.0 Hz), 8.30 s (2H, NH2)
XIIIn 4.27 s (2H, CH2), 7.13 7.35 m (5H, OPh), 7.41 d (2H, 3-H, 5-H, J = 10.0 Hz), 7.48 d (2H, 3-H, 5-H, J =
9.0 Hz), 7.50 d (2H, 2-H, 6-Harom, J = 10.0 Hz), 7.72 s (1H, SCH), 7.96 d (2H, 2-H, 6-H, J = 9.0 Hz),
8.20 s (2H, NH2)
XIIIo 1.21 t (3H, CH3, J = 10.0 Hz), 3.72 s (2H, ArCH2CO2Et), 4.17 q (2H, OCH2, J = 10.0 Hz), 4.31 s (2H,
NCH2CO), 7.43 s (4H, Harom), 7.50 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.78 s (1H, SCH), 7.97 d (2H, 2-H, 6-H,
J = 9.0 Hz), 8.35 s (2H, NH2)
XIIIp 4.20 s (2H, CH2), 6.09 s (2H, OCH2O), 6.98 m (2H, 5-H, 6-Harom), 7.11 d (1H, 2-Harom, J = 0.5 Hz), 7.48 d
(2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H, SCH), 7.94 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.12 s (2H, NH2)
XIIIq 4.29 s (2H, CH2), 7.46 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.58 7.79 m (5H, SCH, 2-H, 3-H, 6-H, 7-Harom), 7.96 d
(2H, 2-H, 6-H, J = 9.0 Hz), 8.01 m (3H, 4-H, 5-H, 8-Harom), 8.14 s (2H, NH2)
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 37 No. 9 2001

1328
VOLOVENKO et al.
Table 2. (Contd.)
Comp.
no.
Chemical shifts , ppm
XIIIr 4.40 s (2H, CH2), 7.49 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.57 7.73 m (4H, SCH, 3-H, 6-H, 7-Harom), 7.90 8.10 m
(6H, 2-H, 6-H; 1-H, 4-H, 5-H, 8-Harom), 8.39 s (2H, NH2)
XIIIs
XIIIt
3.17 t (4H, CH2NCH2, J = 7.0 Hz), 3.77 t (4H, CH2OCH2, J = 7.0 Hz), 4.20 s (2H, NCH2O), 7.05 d (2H, 3-H,
5-H, J = 9.5 Hz), 7.35 d (2H, 2-H, 6-Harom, J = 9.5 Hz), 7.49 d (2H, 3-H, 5-H, J = 9.0 Hz), 7.70 s (1H,
SCH), 7.95 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.20 s (1H, NH), 8.91 s (1H, NH N)
4.22 s (4H, OCH2CH2O), 4.28 s (2H, NCH2CO), 6.95 m (3H, Harom), 7.47 d (2H, 3-H, 5-H, J = 9.0 Hz),
7.69 s (1H, SCH), 7.94 d (2H, 2-H, 6-H, J = 9.0 Hz), 8.20 s (2H, NH2)
XIIIu 2.95 s (6H, NCH3), 4.15 s (2H, CH2), 6.81 d (2H, 3-H, 5-H, J = 9.5 Hz), 7.28 d (2H, 2-H, 6-Harom, J =
9.5 Hz), 7.47 d (2H, 3-H, 5-H, J = 8.5 Hz), 7.67 s (1H, SCH), 7.93 d (2H, 2-H, 6-H, J = 8.5 Hz), 8.20 s
(2H, NH2)
XIIIv 4.28 s (2H, CH2), 7.50 m (6H, 3-H, 5-H, Harom), 7.67 s (1H, SCH), 7.94 d (2H, 2-H, 6-H, J = 8.0 Hz), 8.20 s
(2H, NH2)
XIIIw 4.37 s (2H, CH2), 7.49 m (4H, 3-H, 5-H, 2-H, 6-Harom), 7.70 s (1H, SCH), 7.95 m (4H, 2-H, 6-H, 3-H, 5-H),
8.50 s (2H, NH2), 11.23 s (1H, OH)
XIIIx 2.25 s (3H, CH3), 4.16 s (2H, CH2), 7.49 m (2H, 3-H, 5-H, Harom), 7.79 s (1H, SCH), 8.00 d (2H, 2-H, 6-H,
J = 9.0 Hz), 8.08 s (2H, NH2)
a
Protons of the Ar substituent are denoted as Harom; the other numbers refer to the RC6H4 ring.
and a one-proton singlet in the region 7.6 7.8 ppm;
the latter belongs to proton in position 5 of the
thiazole ring. The amino group gives a signal in the
procedure). Appropriate aromatic amine, 0.003 mol,
was added to a solution of 0.003 mol of 2-(4-aryl-
thiazol-2-yl)-3-oxo-4-chlorobutyronitrile V VII and
0.4 ml (0.003 mol) of triethylamine in 10 15 ml of
dioxane, heated to the boiling point. The mixture was
refluxed for 3 h until initial compound V VII disap-
peared (according to the TLC data). The mixture was
cooled, and the precipitate was filtered off, thoroughly
washed with water, dried, and recrystallized from
1-butanol (compounds XIh, XIo, XIId, XIIj, XIIk,
XIIIa, XIIIf, XIIIk, XIIIs, and XIIIx) or dioxane
(XIb XId, XIi, XIj, XIm, XIn, XIIa XIIc,
XIIe XIIh, XIIm XIIp, XIIr, XIIs, XIIIb XIIIe,
XIIIl XIIIr, and XIIIt XIIIw). The yields of prod-
ucts XI XIII are given in Table 1.
region
8.0 9.0 ppm; it appears as either two
broadened one-proton singlets (due to nonequivalence
of the NH2 protons, one of which is involved in intra-
molecular hydrogen bond) or one broadened two-
proton singlet. In both cases these signals disappear
on addition of D2O. Proton signals of the aryl substit-
uents on the nitrogen atom of the pyrrole ring and in
position 4 of the thiazole ring are located as usually.
Thus, according to the spectral data, thiazolylpyrroles
XI XIII exist as enaminoketone tautomers.
The yields, melting points, and elemental analyses
of compounds XI XIII are given in Table 1, and
Table 2 contains their 1H NMR spectral parameters.
REFERENCES
EXPERIMENTAL
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The progress of reactions was monitored by TLC
on Silufol UV-254 plates using chloroform methanol
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a Pye Unicam SP3-300 spectrometer from samples
pelleted with KBr. The 1H NMR spectra were obtained
on a Bruker WP-100SY instrument (100 MHz).
5-Amino-1-aryl-4-(4-aryl-1,3-thiazol-2-yl)-2,3-di-
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SYNTHESIS OF 5-AMINO-1-ARYL-4-(4-ARYL-1,3-THIAZOL-2-YL)-. . .
1329
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