Phosphorus pentasulfide and Lawesson reagent in synthesis of 1,3-thiazole-4-thiol derivatives

Article abstract of DOI:10.1007/s11176-005-0024-5

Available S-amidophenacylation products of thiols and sulfanylphenols on treatment with phosphorus pentasulfide or, which is better, Lawesson reagent convert into the corresponding 1,3-thiazole-4-thiol derivatives that are easily oxidized with hydrogen pe

Full text of DOI:10.1007/s11176-005-0024-5

Russian Journal of General Chemistry, Vol. 74, No. 9, 2004, pp. 1418 1422. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004,
pp. 1529 1533.
Original Russian Text Copyright
2004 by Belyuga, Brovarets, Drach.
Phosphorus Pentasulfide and Lawesson Reagent
in Synthesis of 1,3-Thiazole-4-thiol Derivatives
A. G. Belyuga, V. S. Brovarets, and B. S. Drach
Institute of Bioorganic and Oil Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received October 28, 2002
Abstract Available S-amidophenacylation products of thiols and sulfanylphenols on treatment with phos-
phorus pentasulfide or, which is better, Lawesson reagent convert into the corresponding 1,3-thiazole-4-thiol
derivatives that are easily oxidized with hydrogen peroxide. The latter reaction was used to introduce a series
of alkyl- or arylsulfonyl groups in the 4 position of the thiazole ring. This general approach significantly
extends the limited range of synthetic procedures for 1,3-thiazole-4-thiol derivatives.
We have already used adducts of carboxamides and
phenylgyoxal and its analogs I to prepare a series of
functional derivatives of azoles and azines [1 3]. In
the present work we showed that available reagents I
pentasulfide or Lawesson reagent, whose application
field has been considered in detail in the reviews [4,
5]. The III
IV transition involves not only sul-
furization of the S-amidophenacylation products, but
also their cyclization. Evidence for this conclusion
comes from the disappearance from the IR spectra of
by means of a simple sequence I
II
III
IV
presented in Scheme 1 can be converted into novel
derivatives of 1,3-thiazole-4-thiol. The key stage of
the process is the reaction of S-amidophenacylation
products and similar compounds with phosphorus
1
two strong bands at 1620 1660 and 1660 1700 cm ,
belonging to stretching vibrations of different car-
bonyl groups in compounds III. The formation of the
Scheme 1.
H
H
R2
O
OH
Cl
O
NH2
O
N
N
H
SOCl2
R2
R2
R1
R1
R1
O
O
O
O
Ia Id, Ih Ik, Im Io
IIa IId, IIh IIk, IIm IIo
R3SH, Et3N
H
3
SR3
SR3
SO2R
N
N
N
P4S10 or RL
H2O2
R2
R2
R1
R1
R2
R1
S
S
O
O
IIIa IIIo
IVa IVo
Va Vf, Vk
R1 = H, R2 = 4-CH3C6H4 (a); R1 = CH3, R2 = C6H5 (b); R1 = CH3, R2 = 4-CH3C6H4 (c); R1 = R2 = C6H5 (d g); R1 =
C6H5; R2 = 4-CH3C6H4 (h); R1 = C6H5, R2 = 2-thienyl (i); R1 = 4-ClC6H4, R2 = 4-FC6H4 (j); R1 = 4-CH3OC6H4, R2 =
C6H5 (k, l); R1 = 2-furyl, R2 = C6H5 (m); R1 = 2-furyl, R2 = 2-thienyl (n); R1 = 2-thienyl, R2 = C6H5 (o); R3 = C2H5
(IIId Vd), C6H5CH2 (IIIm, IIIo, IVm, IVo), C6H5 (IIIe, IIIk Ve, Vk), 4-ClC6H4 (IIIa, IIIb, IIIf, IIIh IIIj, IIIl, IIIo,
IVa, IVa, IVf, IVh IVj, IVl, IVn, Va, Va, Vf), 4-CH3C6H4 (IIIc, IIIg, IVc, IVg, Vc);
S
S
RL = CH3O
P
S
P
OCH3.
S
1070-3632/04/7409-1418 2004 MAIK Nauka/Interperiodica

PHOSPHORUS PENTASULFIDE AND LAWESSON REAGENT
1419
thiazole ring was also confirmed by the disappearance
Scheme 2.
of the broad band of stretching vibrations of associ-
Ts
1
KOH,
t-BuOH
ated N H bond at 3240 3415 cm . Comparison of
R
N
1
S
the H NMR spectra of a series of related pairs of
O
O
R
S
N=C +
Ts
compounds III and IV reveals disappearance of the
>CH NH group as a result of intramolecular cyclo-
condensation that proceeds more directionally when
Lawesson reagent is used instead of phosphorus
pentasulfide. Finally, note that a heterocyclization like
S
R = Ar, 2-furyl [9].
Ts
R
N
NaH
N=C=S
N=C +
RNH
Ts
A
B has already been observed with analogs of
S
compounds III bearing no functional substituents
R = Alk, Ar [10].
ArSO2
to the amide residue [6, 7].
ArSO2
N
N
CH3COSH,
ZnCl2
or RL
R
NaSH
R
R
R
S
N
HN
>
>
>
>
>
>
>
>
>
>
>
>
S
Cl Cl
R = C6H5, (CH3)C [11].
S
O
O
A
B
RSO2
RSO2
Cl
N
N
S=C(NH2)2,
R = H, Alk, Ar, Ht.
Ph
Cl
Ph
Cl Cl
ArSO2
Cl
Thus, the fact that the reactions of compound III
with phosphorus pentasulfide and Lawesson reagent
provide 1,3-thiazole derivatives casts no doubts. The
scope of application of the cyclization III IV proved
to be rather wide, as seen from the structures of the
starting S-amidophenacylation products and their
analogs (Table 1), as well as of the corresponding
1,3-thiazole derivatives containing various alkylsul-
fanyl and arylsulfanyl groups in the 4 position of the
ring (Table 2). Previously 4-arylsulfanyl substitution
of the thiazole fragment was effected via the sequence
R = Alk, Ar [12].
ArSO2
N
N
HX, :B
Cl
X
C
S
Cl
S
X = AlkO, AlkS, ArS, AlkNH, Alk2N, ArNH,
HtNH, etc. [13].
C
D
E [8].
X = AlkO, AlkS, ArS, AlkNH, Alk2N, ArNH, HtNH,
etc [13].
SAr
ArSH,
Et3N
HN
S
HN
S
>
>
>
Cyclization products IV are easily oxidized by
hydrogen peroxide, which was used to prepare a series
of 4-alkyl(aryl)sulfonyl-substituted thiazoles V. In-
spite of the fact that five approaches for introducing
alkyl- or arylsulfonyl groups in the 4 position of the
thiazole ring have been developed, they all, as seen
from Scheme 2, are not universal and fail to provide
most of substituted thiazoles V presented in Table 3.
>
>
>
Cl
Cl
Cl
Cl
C
D
SAr
N
Et3N
>
>
>
S
E
Consequently, the whole sequence I
II
III
IV V studied in this work contributes significantly
into the range of approaches to introducing sulfur-
containing groups in the 4 position of the thiazole ring.
It is quite evident that this approach has a much
narrower application field compared to the cyclization
III IV, since only a few N-(2,2-dichloroethenyl)-
amides of aromatic thiocarboxylic acids are available;
moreover, these compounds can only be used for
preparing substituted 2-aryl-1,3-thiazole-4-thiols. At
EXPERIMENTAL
The IR spectra were measured on a Specord M-80
1
the same time, the transformation III
IV makes
spectrometer in KBr pellets. The H NMR spectra
possible synthesis of 1,3-thiazole-4-thiol derivatives
bearing the hydrogen in the 2 position, as well as
various alkyl, aryl, and heteryl substituents.
were measured on a Varian VXR-300 spectrometer in
DMSO-d6 against internal TMS. The yields, constants,
and elemental analyses are listed in Tables 1 3, and
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

1420
BELYUGA et al.
Table 1. Constants, yields, and elemental analyses of S-amidophenacylation products and their analogs III
Found, %
N
Calculated, %
N
Comp. Yield,
mp, Ca
Formula
no.
%
Cl
S
Cl
S
IIIa
IIIb
IIIc
IIId
IIIe
IIIf
IIIg
IIIh
IIIi
IIIj
IIIk
IIIl
IIIm
IIIn
IIIo
72
86
84
74
78
80
83
88
82
88
72
85
78
72
80
90 92
113 114
136 138
107 109
116 118
114 116
128 130
106 108
110 112
149 151
112 113
115 117
110 112
140 142
146 148
10.06
11.03
4.25
4.34
4.15
4.43
3.78
9.28
10.30
10.68
10.48
10.02
9.72
9.21
8.22
16.78
7.32
8.28
C16H14ClNO2S
C16H11ClNO2S
C17H17NO2S
C17H17NO2S
C21H17NO2S
C21H16ClNO2S
C22H19NO2S
C22H18ClNO2S
C19H14ClNO2S
C21H14Cl2FNO2S
C22H19NO3S
C22H18ClNO3S
C20H17NO3S
C17H12ClNO3S2
C20H17NO2S2
11.09
11.19
4.38
4.42
4.68
4.68
4.03
10.03
10.12
10.71
10.71
9.23
9.75
8.87
8.01
16.53
7.38
8.49
7.78
9.12
16.97
17.45
8.14
9.28
3.17
3.88
8.29
8.92
16.13
8.95
9.14
16.33
3.56
3.87
3.79
3.71
3.99
3.81
8.52
9.24
7.86
8.87
17.15
17.31
8.61
9.38
a
After crystallization from ethanol.
Table 2. Constants, yields, and elemental analyses of substituted 1,3-thiazole-4-thiols IV
Found, %
Calculated, %
N
Comp.
no.
Yield,
%
mp, Ca
Formula
Cl
N
S
Cl
S
b
IVa 61
9.55
10.86
17.95
20.12
18.09
21.13
18.34
17.18
17.93
15.84
24.93
14.87
17.60
15.74
19.23
24.92
26.41
C16H12ClNS2
C16H12ClNS2
C18H17NS2
C17H15NS2
C21H15NS2
11.15
11.15
20.17
20.17
20.59
21.56
18.56
16.89
17.84
16.28
24.92
14.83
17.07
15.64
18.35
25.59
26.32
IVb 54 (82)c
IVc 59
46 48
4.28
4.41
b
IVd 58
IVe 50 (76)
54 56
116 118
98 100
85 87
111 113
125 127
146 147
94 96
130 132
56 58
104 106
79 81
4.37
3.89
3.43
3.86
3.37
3.58
3.01
3.42
8.31
3.92
3.26
3.71
4.71
4.05
3.69
3.90
3.56
3.63
3.24
3.75
3.42
4.01
3.73
3.83
IVf
51
9.12
C21H14ClNS2
C22H17NS2
9.33
IVg 56 (87)
IVh 69
8.64
9.02
15.98
C22H16ClNS2
C19H12ClNS2
C21H12Cl2FNS2
C22H17NOS2
C22H16ClNOS2
C20H15NOS2
C17H10ClNOS3
C20H15NS3
9.00
9.19
16.40
IVi
IVj
55
62 (90)
IVk 58
IVl
57 (84)
3.07
9.34
8.65
9.43
IVm 52
IVn 54
IVo 57
a
b
c
From ethanol. The compound was isolated as an oil and used in further transformations without additional purification. Here and
hereinafter, parenthesized are the yields of the reactions with Lawesson reagent.
1
the H NMR spectra are presented in Table 4.
N-[2-Aryl(heteryl)-1-alkylsulfanyl(arylsulfanyl)-
2-oxoethyl]carboxamides IIIa IIIo. To a solution
of 0.006 mol of compounds IIa IId, IIh IIk, IIm
IIp in 100 ml of anhydrous acetonitrile, 0.066 mol of
triethylamine and 0.066 mol of the corresponding
thiol were added in succession. The resulting mixture
N-[2-aryl(heteryl)-1-hydroxy-2-oxoethyl]carbox-
amides Ia Id, Ih Ik, Im Io and N-[2-aryl(heteryl)-1-
chloro--2-oxoethyl]carboxamides IIa d, IIh IIk,
IIn IIp were prepared by published procedures [1].
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

PHOSPHORUS PENTASULFIDE AND LAWESSON REAGENT
1421
Table 3. Constants, yields and elemental analyses of 4-alkyl(aryl)sulfonyl-substituted 1,3-thiazoles V
Found, %
Calculated, %
Comp. Yield,
mp, Ca
Formula
no.
%
N
S
N
S
Va
Vb
Vc
Vd
Ve
Vf
78
82
92
86
89
90
82
157 159
120 122
134 136
104 106
102 104
118 120
142 144
3.90
3.86
4.02
4.14
3.62
3.34
3.42
18.10
18.62
18.32
19.42
16.65
15.42
15.74
C16H12ClNO2S2
C16H12ClNO2S2
C18H17NO2S2
C17H15NO2S2
C21H15NO2S2
C21H14ClNO2S2
C22H17NO2S2
4.00
4.00
4.08
4.25
3.71
3.40
3.44
18.33
18.33
18.67
19.47
16.99
15.57
15.74
Vk
a
From DMF water, 10:1.
Table 4. 1H NMR spectra of compounds III V
Comp. no.
, ppm (CDCl3)
3
3
IIIb
2.1 s (3H, CH3), 6.60 d (1H, CH, JHH 13.9 Hz), 6.78 d (1H, NH, JHH 13.9 Hz), 7.18 7.93 m (9H, C6H4,
C6H5)
3
IIIf
IIIg
IIIl
6.80 d (1H, CH, JHH 10.8 Hz), 7.20 8.00 m (15H, C6H4, 2C6H5, NH)
2.35 s (3H, CH3), 6.78 d (1H, CH, JHH 10.7 Hz), 7.08 8.03 m (15H, C6H4, 2C6H5, NH)
3
3
3
3.80 s (3H, CH3O), 7.00 d (1H, CH, JHH 11.3 Hz), 7.03 8.03 m (13H, 2C6H4, C6H5), 9.20 d (1H, NH, JHH
11.3 Hz)
IVa
IVb
IVc
IVd
IVe
IVi
2.39 s (3H, CH3), 7.19 7.48 m (8H, 2C6H4), 8.77 s (1H, C2H, thiazole fragment)
2.71 s (3H, CH3), 7.11 7.64 m (9H, C6H5, C6H4)
2.27 s (3H, CH3), 2.36 s (3H, CH3), 2.68 s (3H, CH3), 7.02 7.48 m (8H, 2C6H4)
1.33 s (3H, CH3), 3.24 s (2H, CH3), 7.36 7.95 m (10H, 2C6H5)
3.82 s (3H, OCH3), 7.00 7.92 m (14H, 2C6H5, C6H4)
7.13 7.90 m (12H, C6H4, C6H5, 2-thienyl)
IVl
IVm
Vd
3.85 s (3H, OCH3), 6.90 7.85 m (13H, 2 C6H4, C6H5)
4.45 s (2H, CH2), 7.25 7.97 m (13H, 2C6H5, 2-furyl)
1.26 s (3H, CH3), 3.48 q (2H, CH2), 7.45 7.98 m (10H, 2C6H5)
3.83 s (3H, OCH3), 7.08 7.95 m (14H, 2C6H5, C6H4)
Vk
was left to stand for 12 h at 20 25 C, 50 ml of water
was added, the precipitate that formed was filtered off,
dried, and purified by crystallization.
of anhydrous toluene was heated at 110 C with
stirring for 3 h, and then left to stand for 12 h at 20
25 C. The solvent was removed in a vacuum, and the
residue was treated with 15 ml of 10% aqueous
sodium hydroxide, filtered off, and purified by crys-
tallization from ethanol. Mixed sample of the products
obtained by procedures a and b showed no melting
point depression, and their IR spectra were also
identical.
4-Alkylsulfanyl(arylsulfanyl)-2-R1-5-R2-1,3-
thiazoles IVa IVo. a. A mixture of 0.003 mol of
compound IIIa IIIo, 0.67 g of phosphorus pentasul-
fide, and 30 ml of chlorobenzene was stirred for 2 h
at 100 C. The solvent was removed in a vacuum, after
which 15 ml of 10% aqueous sodium hydroxide and
40 ml of chloroform were added in succession. The
organic layer was separated, dried with anhydrous
magnesium sulfate, the solvent was removed in a
vacuum, and the residue was purified by crystalliza-
tion.
4-Alkylsulfonyl(arylsulfonyl)-2-R1-5-R2-1,3-
thiazoles Va Vf and Vk. To a solution of 0.001 mol
of compound IVa IVf, or Vk in 10 ml of glacial
acetic acid heated to 100 C, 10 ml of 30% hydrogen
peroxide was added in 2-ml portions over the course
of 20 30 min. The resulting mixture was left to stand
for 1 h at 20 25 C. The precipitate that formed was
b. A mixture of compound IIIb, IIIe, IIIg, IIIj,
or IIIl, 0.005 mol of Lawesson reagent [5], and 50 ml
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

1422
BELYUGA et al.
filtered off, washed with water, and purified by crys-
tallization.
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8. Vinogradova, T.K., Turov, V.V., and Drach, B.S., Zh.
Org. Khim., 1990, vol. 26, no. 6, p. 1302.
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