Reactions of α-Halo Ketones with 5-Benzyl-and 5-Phenoxymethyl-2H,3H-1,3,4-oxadiazole-2-thiones

Article abstract of DOI:10.1023/A:1013946509227

Alkylation of 5-substituted 2H,3H-1,3,4-oxadiazole-3-thiones with α-bromo ketones in alkaline solutions yields 5-substituted 2-aroylmethylthio-1,3,4-oxadiazoles; in acidic solutions these compounds re-arrange into 4-aryl-3-arylacetamido-2H,3H-1,3-thiazol-2-ones.

Full text of DOI:10.1023/A:1013946509227

Russian Journal of General Chemistry, Vol. 71, No. 11, 2001, pp. 1754 1758. Translated from Zhurnal Obshchei Khimii, Vol. 71, No. 11, 2001,
pp. 1852 1856.
Original Russian Text Copyright
2001 by Andrushko, Demchenko, Krasovskii, Rusanov, Chernega, Lozinskii.
Reactions of -Halo Ketones with 5-Benzyl-
and 5-Phenoxymethyl-2H,3H-1,3,4-oxadiazole-2-thiones
A. P. Andrushko, A. M. Demchenko, A. N. Krasovskii, E. B. Rusanov,
A. N. Chernega, and M. O. Lozinskii
Chernigov State University of Technology, Chernigov, Ukraine
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received January 13, 2000
Abstract Alkylation of 5-substituted 2H,3H-1,3,4-oxadiazole-3-thiones with -bromo ketones in alkaline
solutions yields 5-substituted 2-aroylmethylthio-1,3,4-oxadiazoles; in acidic solutions these compounds re-
arrange into 4-aryl-3-arylacetamido-2H,3H-1,3-thiazol-2-ones.
It is known that carboxylic acid hydrazides I react
with CS2 in alkaline solutions to give 5-R-2H,3H-
1,3,4-oxadiazole-2-thiones II, which react with -halo
ketones in alkaline solutions to form the correspond-
ing S-substituted compounds III [1 3]. We found that
the reaction pathway and the structure of the products
are largely influenced by pH, nature of the 5-substit-
uent in the substrate, and temperature. For example,
oxadiazoles IIa IIg, when heated in alkaline solutions
with -phenacyl bromides, yield 5-substituted 2-aroyl-
methylthio-1,3,4-oxadiazoles IIIa IIIh, whereas in
acidic solutions the rearrangement products, 4-aryl-
3-arylacetamido-2H,3H-1,3-thiazol-2-ones IVa IVm,
were obtained.
The structures of the rearrangement products was
proved by independent synthesis, and that of IVb, by
single crystal X-ray diffraction. For example, reaction
of potassium (N-phenylacethydrazido)formodithioates
Va and Vb with -halo ketones yielded 4-aryl-3-
arylacetamido-2H,3H-1,3-thiazole-2-thiones VIa VIc.
These compounds, as shown in [4, 5], when treated
with hydrogen peroxide, transform into compounds
1
IVb, IVc, and IVf. The H NMR and IR spectra of
the compounds obtained by different methods are
identical. The yields, constants, elemental analyses,
1
and IR and H NMR spectra of III, IV, and VI are
listed in Tables 1 and 2.
I, II, V, R1 = C6H5 (a), 4-CH3OC6H4 (b), 4-C2H5OC6H4 (c), 2,4-Cl2C6H3O (d), 4-BrC6H4O (e), 4-CH3OC6H4O (f),
5-phenyl-2H-1,2,3,4-tetrazolyl (g). III, R1 = C6H5 (a d), 4-CH3OC6H4 (e, f), 4-C2H5OC6H4 (g), 2,4-Cl2C6H3O (h);
R2 = F (a, h), Cl (b, g), Br (c, f), CH3O (d), H (e); R3 = H (a h). IV, R1 = C6H5 (a d, i), 4-CH3OC6H4 (e, f),
4-C2H5OC6H4 (g), 2,4-Cl2C6H3O (h, j), 4-BrC6H4O (k), 4-CH3OC6H4O (l), 5-phenyl-2H-1,2,3,4-tetrazolyl (m); R2 = F
(a, h), Cl (b, g, m), Br (c, f, k, l), CH3O (d), H (e, i); R3 = H (a e, h m), CH3 (g). VI, R1 = C6H5 (a, b), 4-CH3OC6H4
(c); R2 = Cl (a), Br (b, c); R3 = H (a c).
1070-3632/01/7111-1754$25.00 2001 MAIK Nauka/Interperiodica

REACTIONS OF -HALO KETONES
1755
Table 1. Yields, constants, and elemental analyses of heterocyclic compounds IIIa IIIh, IVa IVm, and VIa VIc
Found, %
Calculated, %
Comp.
no.
Yield, %a
mp,
C
Formula
N
S
N
S
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IVa
IVb
IVc
IVd
IVe
IVf
IVg
IVh
IVi
IVj
IVk
IVl
78
69
74
74
68
73
70
82
124 125
106 107
120 121
123 124
116 117
130 130.5
98 99
129 131
158 159
220 221
241 242
176 177
143 144
164 165
149 150
217 218
185 186
241 242
227 228
212 213
214 215
209.5 211
228 229
198 199
8.43
8.09
7.15
8.19
8.18
6.65
7.17
6.75
8.50
8.08
7.24
8.18
8.21
6.65
7.24
6.73
8.59
5.73
5.87
6.45
20.44
7.71
6.90
6.45
9.68
9.26
8.22
9.37
9.36
7.62
8.21
7.74
9.78
9.34
8.25
9.40
9.43
7.68
8.29
7.78
9.91
6.63
6.72
7.39
7.72
17.84
15.87
14.78
C17H13FN2O2S
C17H13ClN2O2S
C17H13BrN2O2S
C18H16N2O3S
8.49
8.12
7.20
8.23
8.23
6.68
7.20
6.78
8.53
8.12
7.20
8.23
8.23
6.68
7.20
6.78
8.64
5.79
5.91
6.44
20.38
7.76
6.91
6.43
9.71
9.30
8.24
9.42
9.42
7.65
8.24
7.76
9.76
9.30
8.24
9.42
9.42
7.65
8.24
7.76
9.88
6.62
6.76
7.37
7.77
17.82
15.83
14.75
C18H16N2O3S
C18H15BrN2O3S
C19H17ClN2O3S
C17H11Cl2FN2O3S
C17H13FN2O2S
C17H13ClN2O2S
C17H13BrN2O2S
C18H16N2O3S
78, 80
80, 82, 72
86, 85, 75
62, 70
68, 76
80, 85, 77
76, 79
78, 81
79
C18H16N2O3S
C18H15BrN2O3S
C19H17ClN2O3S
C17H11Cl2FN2O3S
C18H16N2O2S
C17H12Br2N2O3S
C17H11BrCl2N2O3S
C18H15BrN2O4S
C18H13ClN6O2S
C17H13ClN2OS2
C17H13BrN2OS2
C18H15BrN2O2S2
82
85
82
75
62
74
71
IVm
VIa
VIb
VIc
a
Yields of compounds IV are given for synthesis procedures a, b, and c, respectively.
The structures of the synthesized compounds were
proved by H NMR and IR spectroscopy. For exam-
is shown in the figure, and its selected geometric
parameters are listed in Table 3.
1
ple, the IR spectra of compounds III contain charac-
teristic absorption bands of the stretching vibrations
1
(C=O) at 1670 1690 cm and (C=N) at 1590
1
1640 cm . In the spectra of compounds IV and VI
the NH stretching vibrations are observed at 2990
1
1
3030 and 3190 3240 cm (Table 2). The H NMR
spectra of oxadiazoles III contain, along with signals
of the aromatic protons, also two-proton singlets of
the methylene groups of the benzyl ( 4.15 4.24 ppm)
or phenoxymethyl ( 4.95 ppm) fragment. The two-
proton singlets of the methylene groups of the phen-
acyl residues are observed at 4.99 5.21 ppm, which
suggests existence of these compounds in the open
1
tautomeric form [6]. The H NMR spectra of IV and
VI contain a singlet of the methine proton of the thi-
azole ring at 6.58 7.31 ppm and an NH signal at
10.9 11.6 ppm (Table 2).
The structure of IVb was proved by single crystal
X-ray diffraction. The general view of the molecule
General view of the molecule of 4-(4-chlorophenyl)-3-
phenylacetamido-2H,3H-1,3-thiazol-2-one (IVb).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

1756
ANDRUSHKO et al.
Table 2. IR and 1H NMR spectra of IIIa IIIh, IVa IVm, and VIa VIc
1
IR spectrum, , cm
1H NMR spectrum, , ppm
Comp.
no.
(CO)
(CN)
(NH)
R1CH2
SCHR3
NH
ArH, m
other signals
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
1690
1670
1674
1678
1672
1670
1670
1640
1580
1610
1590
1610
1590
1592
4.24 s
4.24 s
4.24 s
4.24 s
4.15 s
4.16 s
4.15 s
5.05 s (2H)
5.03 s (2H)
5.04 s (2H)
4.99 s (2H)
5.04 s (2H)
5.03 s (2H)
5.04 s (2H)
7.29 8.11 (9H)
7.29 8.01 (9H)
7.31 7.96 (9H)
7.06 8.01 (9H) 3.86 s (3H, OCH3)
6.84 8.05 (9H) 3.73 s (3H, OCH3)
6.87 7.98 (8H) 3.73 s (3H, OCH3)
6.82 7.83 (8H) 3.95 q (2H, CH2),
1.31 t (3H, CH3)
IIIh
IVa
IVb
IVc
IVd
IVe
IVf
1678
1610
4.95 s
3.48 s
5.21 s (2H)
6.58 s (1H)
6.66 s (1H)
6.66 s (1H)
6.46 s (1H)
6.59 s (1H)
6.66 s (1H)
6.65 s (1H)
6.78 7.65 (7H)
7.04 7.38 (9H)
7.11 7.39 (9H)
7.03 7.55 (9H)
6.88 7.33 (9H) 3.78 s (3H, OCH3)
6.76 7.48 (9H) 3.72 s (3H, OCH3)
6.75 7.52 (8H) 3.73 s (3H, OCH3)
6.78 7.41 (8H) 3.98 q (2H, CH2),
1.32 t (3H, CH3)
1690, 1710 1620 3020, 3192
11.1
11.2
11.2
11.0
11.0
11.1
11.1
1688, 1712 1620 3020, 3192 3.49 q
1680, 1705 1600 3020, 3190 3.48 q
1680, 1692 1610 3020, 3200 3.48 q
1684, 1698 1620 3010, 3198
1690, 1710 1618 3008, 3200 3.39 q
1688, 1710 1640 2990, 3240 3.42 q
3.41 s
IVg
IVh
IVi
IVj
IVk
IVl
IVm
VIa
VIb
VIc
1690, 1708 1620 3018, 3220 4.81 q
1690, 1710 1638 3030, 3200 3.38 q
1688, 1710 1620 3020, 3190 4.68 q
1694, 1710 1618 3020, 3240 4.80 q
1692, 1708 1620 3020, 3220 4.58 q
1680, 1690 1610 3020, 3200 5.76 q
6.64 s (1H)
2.05 s (3H)
6.71 s (1H)
6.70 s (1H)
6.75 s (1H)
6.72 s (1H)
7.14 s (1H)
7.17 s (1H)
7.31 s (1H)
11.2
10.9
11.3
11.2
11.2
11.6
11.6
11.6
11.6
6.72 7.58 (7H)
6.92 7.45 (10H)
6.79 7.61 (8H)
6.72 7.65 (7H)
6.78 8.01 (8H) 3.71 s (3H, OCH3)
7.40 8.10 (9H)
7.14 7.40 (9H)
7.06 7.55 (9H)
6.78 7.82 (8H) 3.74 s (3H, OCH3)
1690
1690
1690
1618 3020, 3200 3.42 q
1620 3020, 3200 3.51 q
1620 3020, 3198 3.39 q
Table 3. Selected bond lengths (d, ) and bond angles ( , deg) in the molecule of IVb
Bond
Cl1 C7
S1 C1
S1 C3
O1 C3
O2 C10
N1 N2
N1 C3
d
Angle
Bond
d
Angle
1.729(6)
1.727(6)
1.770(7)
1.194(6)
1.224(5)
1.375(6)
1.383(7)
C1S1C3
N2N1C3
N2N1C2
C3N1C2
C10N2N1
S1C1C2
N1C2C1
91.6(3)
119.5(3)
122.6(4)
116.3(5)
120.6(5)
113.7(4)
111.4(5)
N1 C2
1.410(6)
1.333(6)
1.319(7)
1.493(7)
1.481(8)
C1C2C4
N1C2C4
O1C3N1
S1C3O1
129.3(5)
119.3(5)
126.5(6)
126.7(5)
106.8(5)
120.2(5)
125.2(5)
114.6(5)
N2 C10
C1 C2
C10 C11
C11 C12
S1C3N1
O2C10N2
O2C10C11
N2C10C11
The thiazoline ring S1N1C1 3 is planar within
0.026(3) , and the O1, N2, and C4 atoms deviate
the S1 C3 bond [1.770(7) ], and the length of
the formally ordinary N1 C3 bond [1.383(7) ],
owing to the n(N1) *(C3=O1) conjugation, is notice-
ably smaller than the common values for N(sp2)
C(sp2) bonds (1.43 1.45 ) [10, 11]. Similarly,
the n(N2) *(C10=O2) conjugation results in shorten-
from this plane by 0.072(8), 0.183(7), and 0.044(8)
,
respectively. The geometry of this ring is usual. As in
other thiazoline systems [7 9], in the molecule of IVb
the S1 C1 bond [1.727(6) ] is somewhat shorter than
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

REACTIONS OF -HALO KETONES
1757
ing of the N2 C10 bond to 1.333(6) . The N1 and N2
atoms have a practically trigonal planar configuration,
with the bond angle sums amounting to 358.4 and
358.6 , respectively. Owing to steric interactions,
the benzene ring C4 9 is turned by 55.0 relative
to the thiazoline ring plane. The N1N2C10H2N is
almost orthogonal to the thiazoline ring (the corre-
sponding dihedral angle is 81.6 ), which may be due
not only to steric interactions, but also to repulsion
between the lone electron pairs of the N1 and N2
atoms. In the crystal of IVb, the molecules are
linked in infinite chains by fairly strong [12, 13] in-
termolecular hydrogen bonds N2 H2N O2. The main
geometric parameters of these hydrogen bonds are as
follows: N2 O2 2.766(5), N2 H2N 0.76(4), H2N O2
2.035(4) ; N2H2NO2 angle 165.6(3) .
Table 4. Atomic coordinates ( 104) and their equivalent
2
isotropic thermal parameters Ueq
of IVb
(
103) in the molecule
Atom
x
y
z
Ueq
Cl1
S1
1644(2)
786(1)
7331(1)
194(1)
240(3)
2280(3)
1624(4)
2081(4)
1632(5)
2281(5)
456(5)
3524(4)
4120(5)
5290(5)
5868(5)
5288(5)
4129(5)
2447(4)
3085(6)
3487(7)
2955(9)
3329(14)
4245(17)
4742(11)
4371(7)
2249(29)
3937(2)
3695(2)
3460(4)
5860(4)
3478(4)
3550(5)
3789(6)
3668(5)
3530(5)
3715(6)
4839(6)
4923(7)
3856(7)
2707(7)
2642(6)
4769(5)
4653(6)
6003(7)
6576(9)
7816(13)
8474(14)
7920(12)
6685(8)
2868(41)
110(1)
68(1)
72(1)
61(1)
44(1)
47(1)
60(2)
47(1)
54(2)
47(1)
61(2)
72(2)
66(2)
68(2)
55(2)
44(1)
74(2)
75(2)
108(3)
172(6)
198(12)
170(7)
103(3)
1(11)
O1
2545(3)
3134(2)
2061(3)
2939(3)
563(4)
O2
N1
N2
C1
C2
1284(4)
1958(5)
1363(4)
1138(4)
1226(5)
1527(4)
1734(4)
1656(4)
3424(4)
4294(4)
4844(5)
5658(6)
6152(7)
5866(12)
5070(12)
4557(7)
3087(24)
C3
C4
C5
C6
EXPERIMENTAL
C7
C8
The IR spectra of III, IV, and VI (KBr pellets)
C9
1
were taken on a UR-20 spectrophotometer. The H
C10
C11
C12
C13
C14
C15
C16
C17
H2N
NMR spectra were measured on a Bruker-300 spec-
trometer with a working frequency of 300 MHz (solu-
tions in DMSO-d6, internal reference TMS). The mass
spectra were recorded on a Varian MAT-311A spec-
trometer.
Single crystal X-ray diffraction study of IVb was
performed at room temperature on an Enraf Nonius
CAD-4 automatic four-circle diffractometer (MoK
radiation, graphite monochromator, scanning rate ratio
/2 1.2,
22 , sphere segment 0
h
15, 0
k
12, 10max
l
10). The unit cell parameters and
a chain of hydrogen bonds and refined isotropically).
The structure was refined to R1(F) 0.0618 and
RW(F2 ) 0.1360, GOF 1.087. The residual electron
density from the differential Fourier series was 0.20
and 0.23 e/ 3. The atomic coordinates are listed in
Table 4.
the orientation matrix of the crystal of IVb (0.2
0.3 0.55 mm) were determined from 22 reflec-
tions with 12 < < 13 . A total of 2082 reflections
were measured, including 1991 unique reflections
(averaging R factor 0.029). Crystal data: monoclinic,
a 14.557(3), b 11.759(2), c 9.690(2)
;
100.48(3) ,
5-Substituted 2-aroylmethylthio-1, 3, 4-oxadi-
azoles IIIa IIIh. A solution of 10 mmol of -halo
ketone in 20 ml of ethanol was added to a solution of
10 mmol of oxadiazole IIa IIg in 40 ml of aqueous
ethanol, containing 10 mmol of KOH. The mixture
was allowed to stand for 10 15 h at room tempera-
ture, after which 50 60 ml of water was added, and
the colorless precipitate was filtered off, washed with
water, and recrystallized from ethanol.
3
1
V 1631.0(6) 3, Z 4, dcalc 1.40 g cm , 0.372 mm ,
F(000) 712, space group P21/c (no. 14). The struc-
ture was solved by the direct method and refined by
full-matrix least-squares in the anisotropic approxima-
tion using the SHELXS and SHELXL 93 programs
[14, 15]. In the refinement we used 1267 reflections
with I > 2 (I) {212 refined parameters, 5.98 reflec-
tions per parameter, weight scheme = 1/[ (Fo2) +
2
(0.0684P)2 + 0.2635P], P = (Fo2 + 2Fc2)/3, ratio of
the maximal/average shift to the error in the last cycle
0.024/0.002)}. Correction was made for anomalous
scattering; corrections for absorption were not in-
troduced. All hydrogen atoms were revealed and re-
4-Aryl-3-arylacetamido-2H,3H-1,3-thiazol-2-ones
IVa IVm. a. A mixture of 10 mmol of 2H,3H-1,3,4-
oxadiazole-2-thione Ia Ig and 10 mmol of -halo
ketone in 20 30 ml of 2-propanol was refluxed for
2 3 h, cooled, and filtered; the colorless precipitate
was recrystallized from ethanol.
fined with fixed positional and thermal parameters
2
Uiso = 0.08
(except the H2N atom involved in
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 71 No. 11 2001

1758
ANDRUSHKO et al.
3. Sasaki, T., Ohno, M., Ito, E., and Asai, K., Tetra-
b. A solution of 10 mmol of 5-substituted 2-aroyl-
hedron, 1984, vol. 40, no. 14, pp. 2703 2709.
methylthio-1,3,4-oxadiazole IIa IIh in 40 ml of eth-
anol was refluxed for 1 h with 5 ml of concd. HCl,
cooled, and filtered; the precipitate was recrystallized.
4. JPN Patent 80-89272, 1980, Chem. Abstr., 1981,
vol. 94, no. 30743.
5. Ege, G., Arnold, P., and Noronha, R., Lieb. Ann.,
c. A 10-mmol portion of 4-aryl-3-arylacetamido-
2H,3H-1,3-thiazole-2-thione VIa VIc was dissolved
in 30 ml of 2 N aqueous NaOH, and 13 ml of 20%
aqueous hydrogen peroxide was added with cooling
on a water ice bath. The mixture was allowed to stand
at room temperature for 10 h and neutralized with
2 N HCl. The precipitate was filtered off, washed with
water, and recrystallized.
1979, no. 5, pp. 656 674.
6. Krasovskii, A.N., Roman, A.B., Klyuev, N.A., Kal-
mazan, T.I., Soroka, I.I., and Klyuev, S.M., Khim.
Geterotsikl. Soedin., 1982, no. 4, pp. 774 777.
7. Shin, W. and Kin, Y.Ch., J. Am. Chem. Soc., 1986,
vol. 108, no. 22, pp. 7078 7082.
8. Dolling, W., Kischkies, K., Stroehl, D., Heine-
mann, F., and Hartung, H., Phosphorus, Sulfur, Sil-
icon, 1992, vol. 69, no. 2, pp. 267 271.
4-Aryl-3-arylacetamido-2H,3H-1,3-thiazole-2-thi-
ones VIa VIc. A solution of 1.12 g of KOH in 10 ml
of water and 20 mmol of CS2 were added at 0 5 C to
a solution of 20 mmol of phenylacetic (Ia) or phen-
oxyacetic (Ib) acid hydrazide in 50 ml of methanol.
The mixture was stirred for 2 h at 5 C, after which
a solution of 20 mmol of -halo ketone in 25 ml of
methanol was added. The resulting mixture was al-
lowed to stand for 10 h at room temperature. Then
5 ml of concentrated HCl was added, the mixture was
refluxed for 1 h, and, after cooling, the colorless pre-
cipitate was filtered off and recrystallized from ethan-
ol or glacial acetic acid.
9. Heinemann, F., Dolling, W., and Hartung, H., Acta
Crystallogr., Sect. C, 1992, vol. 48, no. 2,
pp. 305 307.
10. Alder, R.W., Goode, N.C., King, T.J., Mellor, J.M.,
and Miller, B.W., Chem. Commun., 1976, no. 5,
pp. 173 174.
11. Burke-Laing, M. and Laing, M., Acta Crystallogr.,
Sect. B, 1976, vol. 32, no. 12, pp. 3216 3224.
12. Kuleshova, L.N. and Zorkii, P.M., Acta Crystallogr.,
Sect. B, 1981, vol. 37, no. 7, pp. 1363 1366.
13. Bertolasi, V., Gilli, P., Ferretti, V., and Gilli, G.,
Acta Crystallogr., Sect. B, 1995, vol. 51, no. 6,
pp. 1004 1015.
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