A convenient procedure for introducing arylsulfanyl and heterylsulfanyl groups into the 5 position of the oxazole ring

Article abstract of DOI:10.1007/s11176-005-0023-6

Available (2-aryl-5-mesyl-1,3-oxazol-5-yl)triphenylphosphonium salts readily react with sodium thiophenolates and their heterocyclic analogs by way of substitution of the mesyl group by an arylsulfanyl or a heterylsulfanyl group. Treatment of the products

Full text of DOI:10.1007/s11176-005-0023-6

Russian Journal of General Chemistry, Vol. 74, No. 9, 2004, pp. 1414 1417. Translated from Zhurnal Obshchei Khimii, Vol. 74, No. 9, 2004,
pp. 1524 1528.
Original Russian Text Copyright
2004 by Golovchenko, Brovarets, Drach.
A Convenient Procedure for Introducing Arylsulfanyl
and Heterylsulfanyl Groups
into the 5 Position of the Oxazole Ring
A. V. Golovchenko, V. S. Brovarets, and B. S. Drach
Institute of Bioorganic and Oil Chemistry, National Academy of Sciences of Ukraine, Kiev, Ukraine
Received August 13, 2002
Abstract Available (2-aryl-5-mesyl-1,3-oxazol-5-yl)triphenylphosphonium salts readily react with sodium
thiophenolates and their heterocyclic analogs by way of substitution of the mesyl group by an arylsulfanyl or
a heterylsulfanyl group. Treatment of the products with sodium hydroxide results in their mild dephosphoryla-
tion, which was used for preparative synthesis of a series of 2-aryl-5-arylsulfanyl(heterylsulfanyl)-1,3-
oxazoles.
Previously we found that substituted vinylphos-
phonium salts of the general formula Cl2C=C
(NHCOR)+PPh3An regioselectively react with sodium
sulfide to form stable mesomeric ylide betaines I and
used the latter to success for preparing a series of
5-alkylsulfanyl-2-R-1,3-oxazoles [1 3]. In the present
work, as seen from the scheme below, we studied the
conversions of ylide betaines I, leading not only to
S-methylation products II, but also to substituted
oxazoles III VII. The most important of the products
were found to be new available reagents III containing
adjacent mesyl and triphenylphosphonium groups in
the oxazole ring. They readily and selectively reacted
with sodium thiophenolates or their heterocyclic
analogs, and this reaction proved to be a key step in
(2-aryl-5-chloro-1,3-oxazol-4-yl)triphenylphospho-
nium chlorides. Therefore, in the synthesis of phos-
phonium salts V, we considered it expedient to
replace them by the available and analytically pure
reagents III.
In summary it can be said that the assignment of
compounds I VIII to 1,3-dioxazole derivatives casts
no doubts, since the structure of one of the first
members of the series of ylide betaines I with R = H,
as well as its reaction product with methyl iodide was
rigorously proved by X-ray diffraction analysis [5].
Moreover, successive treatment of ylide betaine Ia
with hydrogen peroxide and sodium hydroxide gave
2-phenyl-1,3-dioxazole which was also synthesized
by independent methods [2]. In addition, the modifica-
tion of the 5-substituent was followed, as seen from
the synthetic sequence III
V
VI
VII. As a
result, we could introduce into the 5 position of the
oxazole ring four types of sulfur-containing groups:
ArS, HtS, ArSO2, and HtSO2. Furthermore, the
4-Ph3P+ group could be replaced by hydrogen. The
application scope of this convenient synthetic ap-
proach to 5-mercapto-1,3-oxazole derivatives is not
restricted by the examples in the scheme below, since
1
Table 1, by H NMR spectroscopy which gave evi-
dence for the conversion of the methylsulfanyl group
into mesyl in the course of the nucleophilic substitu-
tion reaction II
phenylphosphonium group by the alkaline cleavage
VI. It is interesting that related phosphonium
V and the elimination of the tri-
V
salts V and VII differently react with alkalis. In the
first case, the major process is C P bond cleavage and
in the second, dephosphorylation is attended with C S
bond cleavage. Therefore, 5-arylsulfonyl-2-R-1,3-
oxazoles should be prepared using the sequence V
each of the steps of the sequence I
II
III
V
is obviously rather general in nature. Moreover, this
approach, even though it involves many steps, offers
advantages over other known syntheses of a few
representatives of phosphonium salts V, such as con-
densation of reagent IV and its analogs with thiols
[3, 4] or reaction of ylide betaines I with arenedia-
zonium salts [3]. The latter method has a fairly
narrow field of uses and, in addition, is insufficiently
VI
VII.
EXPERIMENTAL
The IR spectra were obtained on a Specord M-80
selective. The condensation IV
more selectively, but the chlorination of ylide betaines
I is complicated [3, 4] and fails to provide isolable
V occurs much
instrument in KBr pellets. The 1H NMR spectra were
measured on a Varian VXR-300 spectrometer in
CDCl3 or (CD3)2SO, internal reference TMS (Table 1).
1070-3632/04/7409-1414 2004 MAIK Nauka/Interperiodica

A CONVENIENT PROCEDURE FOR INTRODUCING ARYLSULFANYL
+PPh3
1415
...
N
.
.
1) MeI; 2) NaClO4
Cl2
.
.
.
.
..
.
S
R
R = Ph
O
Ia, Ib
+
+
+
PPh3ClO4
PPh3ClO4
PPh3ClO4
N
N
N
H2O2
R
SMe
R
SO2Me
R
Cl
O
O
O
IV
IIa, IIb
IIIa, IIIb
R SNa
+
PPh3ClO4
1) R SNa
Et3N;
R SNa
N
2) NaClO4
R
SR
O
Va Vh
NaOH
H2O2
+
PPh3ClO4
N
N
O
N
NaOH
H2O2
Ph
SO2R
R
SR
R
SO2R
O
O
VIIa, VIIb, VIId VIIf
VIIIa, VIIIb, VIIId VIIIe
VIa, VIb, VId VIh
R = C6H5 (Ia IIIa, Va, Vc, VIa VIIIa), 4-CH3C6H4 (Ib IIIb, Vb, Vd Vh, VIb, VId VIg, VIIb, VIId VIIf, VIIIe,
VIIIg); R = C6H5 (Vb VIIb), 4-ClC6H4 (Va, Vd VIIa, VIId, VIIIa), 4-CH3C6H4 (Vc, Ve, VIe VIIIe), benzotriazol-2-
yl (Vf VIIf), 5-(4-bromophenyl)-1,2,4-triazol-3-yl (Vg, VIg, VIIIg), 4-hydroxy-6-methylpyrimidin-2-yl (Vh, VIh).
Table 1. 1H NMR spectra of the synthesized compounds
Comp. no.
, ppm (CDCl3)
IIa
2.63 s (3H, CH3S), 7.56 8.10 m (20H, 4C6H5)
IIIa
IIIb
Vb
3.35 s (3H, CH3SO2), 7.65 8.12 m (20H, 4C6H5)
2.46 s (3H, CH3), 3.34 s (3H, CH3SO2), 7.42 8.15 m (19H, 3C6H5, C6H4)
2.42 s (3H, CH3), 7.25 7.96 m (24H, 4C6H5, C6H4)
Vd
2.41 s (3H, CH3), 7.26 7.94 m (23H, 3C6H5, 2C6H4)
Ve
Vf
2.34 s (3H, CH3), 2.41 s (3H, CH3), 7.20 8.05 m (23H, 3C6H5, 2C6H4)
2.43 s (3H, CH3), 7.27 8.02 m (23H, 3C6H5, 2C6H4)
Vg
Vh
2.41 s (3H, CH3), 7.29 7.95 m (24H, 3C6H5, 2C6H4, NH)
2.31 s (3H, CH3), 3.41 s (3H, CH3), 7.27 7.96 m (21H, 3C6H5, CH)a
7.22 8.09 m (9H, C6H5, C6H4), 7.49 s (1H, C4 H)
VIa
VIb
VId
VIe
VIf
VIg
VIIa
VIIb
VIId
VIIe
VIIf
2.40 s (3H, CH3), 7.21 7.93 m (9H, C6H5, C6H4), 7.45 s (1H, C4 H)
2.40 s (3H, CH3), 7.20 7.95 m (8H, 2C6H4), 7.45 s (1H, C4 H)
2.31 s (3H, CH3), 2.40 s (3H, CH3), 7.10 7.92 m (8H, 2C6H4), 7.40 s (1H, C4 H)
2.45 s (3H, CH3), 7.26 8.10 m (8H, 2C6H4), 7.67 s (1H, C4 H)
2.44 s (3H, CH3), 3.26 s (3H, CH3), 7.33 d, 8.00 d (4H, C6H4), 7.26 s, 7.81 s (2H, CH, C4 H)a
7.45 8.05 m (9H, C6H5, C6H4), 7.85 s (1H, C4 H)
2.41 s (3H, CH3), 7.27 8.12 m (9H, C6H5, C6H4), 7.83 s (1H, C4 H)
2.42 s (3H, CH3), 7.26 8.14 m (8H, 2C6H4), 7.83 s (1H, C4 H)
2.41 s (3H, CH3), 2.44 s (3H, CH3), 7.26 7.92 m (8H, 2C6H4), 7.79 s (1H, C4 H)
2.41 s (3H, CH3), 7.26 8.24 m (8H, 2C6H4), 8.08 s (1H, C4 H)
VIIIe 2.44 s (3H, CH3), 2.46 s (3H, CH3), 7.27 7.98 m (23H, 3C6H5, 2C6H4)
a
Signal of the N H proton was not found.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

1416
GOLOVCHENKO et al.
Table 2. Constants, yields, and elemental analyses of phosphorylated oxazoles II, III, V, and VIII
Found, %
P
Calculated, %
P
Comp. Yield,
mp, Ca
Formula
no.
%
Cl
S
Cl
S
IIa
IIb
IIIa
IIIb
Va
Vb
Vc
Vd
Ve
Vf
Vg
Vh
VIIIa
VIIIe
VIIIg
95
97
90
88
73
75
70
71
78
83
64
66
78
75
60
234 235
6.33
6.15
5.94
5.79
10.85
5.49
5.53
10.31
5.49
5.06
4.37
5.52
5.35
5.22
5.09
4.63
4.80
4.83
4.57
4.68
4.40
3.89
4.52
4.39
4.49
3.60
5.68
5.56
5.39
5.28
4.89
5.05
5.02
4.75
4.81
9.25
4.02
4.77
4.62
4.65
3.92
C28H23ClNO5PS
C29H25ClNO5PS
C28H23ClNO7PS
C29H25ClNO7PS
C33H24Cl2NO5PS
C34H27ClNO5PS
C34H27ClNO5PS
C34H26Cl2NO5PS
C35H29ClNO5PS
C35H26ClN2O5PS2
C36H27BrClN4O5PS
C33H27N3O6PS
6.42
6.26
6.07
5.93
10.93
5.64
5.64
10.70
5.52
5.17
4.58
5.37
10.42
5.26
4.40
5.61
5.46
5.30
5.19
4.78
4.93
4.93
4.66
4.82
4.52
4.00
4.69
4.52
4.59
3.84
5.81
5.66
5.49
5.37
4.94
5.11
5.11
4.84
4.99
9.36
4.14
4.86
4.71
4.76
3.98
195 198
242 244
220 221
169 171
180 182
151 152
182 184
150 152
162 163
196 198
245 246 (decomp.) 5.26
151 152
150 152
251 253
10.24
5.12
4.32
C33H24Cl2NO7PS
C35H29ClNO7PS
C36H27BrClN4O7PS
a
After recrystallization from methanol.
Table 3. Constants, yield, and elemental analyses of substituted oxazoles VI and VII
Found, %
Calculated, %
Comp. Yield,
mp, Ca
Formula
no.
%
N
S
N
S
VIa
VIb
VId
VIe
84
80
83
75
60
91
65
71
70
68
60
75
63 64
76 78
78 80
92 93
136 137
195 196
270 271 (decomp.)
152 154
160 161
169 170
126 127
170 171
4.72
5.18
4.61
4.89
8.62
7.68
14.14
4.29
4.64
4.05
4.34
7.78
11.03
12.02
10.70
11.38
19.67
13.60
10.82
9.94
10.63
9.49
10.15
17.81
C15H10ClNOSb
C16H13NOS
4.87
5.24
4.64
4.98
8.63
7.76
14.04
4.38
4.68
4.20
4.46
7.86
14.14
11.99
10.62
11.40
19.77
13.56
10.71
10.03
10.71
9.61
C16H12ClNOSc
C17H15NOS
VIf
C17H12N2OS2
C18H13BrN4OSd
C15H13N3O2S
C15H10ClNO3Se
C16H13NO3S
C16H12ClNO3S
C17H15NO3S
C17H12N2O3S2
VIg
VIh
VIIa
VIIb
VIId
VIIe
VIIf
10.23
17.99
a
b
c
After recrystallization from methanol. Found Cl, %: 12.26. Calculated Cl, %: 12.32. Found Cl, %: 11.66. Calculated Cl, %:
d
e
f
11.74. Found Br, %: 19.18. Calculated Br, %: 19.33. Found Cl, %: 11.02. Calculated Cl, %: 11.09. Found Cl, %: 10.54.
Calculated Cl, %: 10.62.
The constants, yields, and elemental analyses of newly
synthesized compounds are given in Tables 2 and 3.
0.01 mol of compound Ia or Ib in 30 ml of methanol,
the mixture was heated at 35 40 C for 5 min until the
precipitate had dissolved completely and cooled to
20 25 C, after which 5 ml of saturated aqueous
sodium perchlorate and 10 ml of water were added.
The precipitate was filtered off and washed with
water. Compounds IIa and IIb were purified by re-
crystallization.
2-Aryl-4-(triphenylphosphonio)-1,3-oxazole-5-thio-
lates Ia and Ib were prepared as described in [2].
[5-(Methylsulfanyl)-2-aryl-1,3-oxazol-4-yl]tri-
phenylphosphonium perchlorates IIa and IIb. Me-
thyl iodide, 0.03 mol, was added to a suspension of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004

A CONVENIENT PROCEDURE FOR INTRODUCING ARYLSULFANYL
1417
1
(2-Aryl-5-mesyl-1,3-oxazol-4-yl)triphenylphos-
phonium perchlorates IIIa and IIIb. Hydrogen per-
oxide, 30 ml of 30% aqueous solution, was added
over the course of 0.5 h to a solution of 0.01 mol of
compound IIa or IIb in 20 ml of glacial acetic acid,
heated to 100 C. The mixture was refluxed for 2 h
and cooled to 20 25 C, after which 10 ml of saturated
aqueous sodium perchlorate and 20 ml of water were
added. The precipitate was filtered off and washed
with water. Compounds IIIa and IIIb were purified
by recrystallization.
lization. Compound VIh: IR spectrum, , cm : 1660
(C=O), 3050 3150 (NH assoc.)
5-Arylsulfonyl-2-phenyl(p-tolyl)-1,3-oxazoles
VIIa, VIIb, VIId, and VIIe. Hydrogen peroxide,
30 ml of 30% aqueous solution, was added in three
portions over the course of 3 h to a solution of
0.001 mol of compound VIa, VIb, VId, or VIe in 10
ml of glacial acetic acid, heated to 100 C. The mix-
ture was cooled to 20 25 C and diluted with 5 ml of
water. The precipitate that formed was filtered off and
recrystallized.
[5-Arylsulfanyl(heterylsulfanyl)-2-phenyl(p-
tolyl)-1,3-oxazol-4-yl)triphenylphosphonium per-
chlorates Va Vh. a. Sodium (arylsulfanyl)phenolate
or its heteryl analog, 0.0011 mol, was added to a
suspension of 0.001 mol of phosphonium salt IIIa or
IIIb in 10 ml of absolute methanol. The mixture was
stirred at 20 25 C for 48 h, the precipitate that formed
was filtered off, and compounds Va Vh were purified
by recrystallization. Compound Vh: IR spectrum, ,
(5-Benzothiazol-2-yl)sulfonyl-2-p-tolyl-1,3-
oxazole (VIIf) was prepared from compound VIf as
described above.
[5-Arylsulfonyl-2-phenyl(p-tolyl)-1,3-oxazol-4-
yl)triphenylphosphonium perchlorates VIIIa and
VIIIe were prepared like compounds IIIa and IIIb by
oxidation of phosphonium salts Va and Vb with
hydrogen peroxide.
1
cm : 1655 (C=O), 3000 3130 (NH assoc.)
[[5-(4-Bromophenyl)-1,2,4-triazol-3-yl]sulfonyl-
2-p-tolyl-1,3-oxazol-4-yl]triphenylphosphonium
perchlorate (VIIIg) was prepared like compounds
IIIa and IIIb from phosphonium salt Vg. IR spec-
b. p-Thiocresol, 0.0021 mol, and 1 ml of pyridine
were added to a suspension of 0.002 mol of phos-
phonium salt IIIb in 15 ml of dry dioxane. The mix-
ture was refluxed for 8 h and, after addition of 3 ml
of 30% aqueous sodium perchlorate, allowed to stand
for 12 h. The precipitate was filtered off, washed with
water and methanol, and dried at 100 C in an oil-
pump vacuum. Compound Ve: yield 65 68%, mp
150 152 C (from methanol). Mixed sample of com-
pound Ve prepared by procedures a and b gave no
melting point depression.
1
trum, , cm : 3050 3150 (NH assoc.).
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Obshch. Khim., 1983, vol. 53, no. 9, p. 2015.
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tolyl)-1,3-oxazoles VIa, Vb, and Vd Vg. Saturated
aqueous sodium hydroxide, 0.5 ml, was added to a
suspension of 0.001mol of phosphonium salt Va, Vb,
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fluxed for 10 min, and the precipitate that formed was
filtered off. The products were purified by recrystal-
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 74 No. 9 2004