Hypervalent iodine in synthesis. 48. A one-pot convenient procedure for the synthesis of 2-mercaptothiazoles by cyclocondensation of ketones with [hydroxy(tosyloxy)iodo]-benzene and ammonium dithiocarbamate

Article abstract of DOI:10.1081/SCC-100000532

α-Tosyloxylation of ketones with [hydroxy(tosyloxy)iodo]-benzene (HTIB), followed by treatment with ammonium dithiocarbamate, provides a one-pot convenient procedure for the synthesis of 2-mercaptothiazoles with good yields.

Full text of DOI:10.1081/SCC-100000532

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HYPERVALENT IODINE IN SYNTHESIS. 48. A ONE-POT
CONVENIENT PROCEDURE FOR THE SYNTHESIS OF 2-
MERCAPTOTHIAZOLES BY CYCLOCONDENSATION OF
KETONES WITH [HYDROXY(TOSYLOXY)IODO]-BENZENE
AND AMMONIUM DITHIOCARBAMATE
a
b
Peng-Fei Zhang & Zhen-Chu Chen
a
Department of Chemistry , Zhejiang University (Xi-Xi Campus) , Hangzhou, 310028,
People's Republic of China
b
Department of Chemistry , Zhejiang University (Xi-Xi Campus) , Hangzhou, 310028,
People's Republic of China
Published online: 09 Nov 2006.
To cite this article: Peng-Fei Zhang & Zhen-Chu Chen (2001) HYPERVALENT IODINE IN SYNTHESIS. 48. A ONE-POT
CONVENIENT PROCEDURE FOR THE SYNTHESIS OF 2-MERCAPTOTHIAZOLES BY CYCLOCONDENSATION OF KETONES WITH
[HYDROXY(TOSYLOXY)IODO]-BENZENE AND AMMONIUM DITHIOCARBAMATE, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 31:3, 415-420, DOI: 10.1081/SCC-100000532
To link to this article: http://dx.doi.org/10.1081/SCC-100000532
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SYNTHETIC COMMUNICATIONS, 31(3), 415–420 (2001)
HYPERVALENT IODINE IN SYNTHESIS. 48.
A ONE-POT CONVENIENT PROCEDURE
FOR THE SYNTHESIS OF
2-MERCAPTOTHIAZOLES BY
CYCLOCONDENSATION OF KETONES
WITH [HYDROXY(TOSYLOXY)IODO]-
BENZENE AND AMMONIUM
DITHIOCARBAMATE
∗
Peng-Fei Zhang and Zhen-Chu Chen
Department of Chemistry, Zhejiang University (Xi-Xi
Campus), Hangzhou 310028, People’s Republic of China
ABSTRACT
α-Tosyloxylation of ketones with [hydroxy(tosyloxy)iodo]-
benzene (HTIB), followed by treatment with ammonium dithiocar-
bamate, provides a one-pot convenient procedure for the synthesis
of 2-mercaptothiazoles with good yields.
Thiazoles, particularly 2-mercaptothiazoles, have become increasingly im-
portant in pharmaceutical, biochemical, and technical fields (1–6). Recently,
Prakash and Saini (7) reported a useful synthesis of 2-mercaptothiazoles. The
approach involves hypervalent iodine oxidation of acetophenones with
∗
Corresponding author.
415
Copyright ꢀC 2001 by Marcel Dekker, Inc.
www.dekker.com

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4
16
ZHANG AND CHEN
O
OH
O
PhI
R
N
NH CSSNH (2)
OTs
CH CN, reflux
2
4
RCCH R1
RCCHR1
OTs
2
SH
CH CN + H O, reflux
3 2
3
R1
S
(1)
(3)
Scheme 1.
[hydroxy(tosyloxy)iodo]benzene, followed by treatment with potassium thiocy-
anate to offer corresponding α-thiocyanatoacetophenones and cyclization of α-
thiocyanatoacetophenones using NH2C(S)NH2/HCl. Although it offers a superior
alternative to the existing synthesis (8–21), which contain the use of lachrymatory
and toxic α-halogenoketones, the overall yield is low. For example, the yield of
4-(p-chlorophenyl)-2-mercaptothiazole is only 20%.
In connection with our programs to utilize hypervalent iodine compounds in
organic synthesis (22), we found that α-tosyloxyketones, generated from ketones
by the oxidation with [hydroxy(tosyloxy)iodo]benzene, can react with ammonium
dithiocarbamate directly to give 2-mercaptothiazoles. Now we would like to report
our result, a one-pot procedure for the synthesis of 2-mercaptothiazoles starting
from ketones. α-Tosyloxylation of ketones with [hydroxy(tosyloxy)iodo]benzene
in acetonitrile, followed by treatment with ammonium dithiocarbamate, afforded
2-mercaptothiazolesin40–58%overallyieldswithoutisolationofanyintermediate
(
Sch. 1). The results are summarized in Table 1.
This one-pot methodology proved quite efficient irrespective of the ketones
used; acetophenones, aliphatic ketones, and β-diketones were successfully em-
ployed. All acetophenones with different substituents in the para position of aro-
matic ring (Entries 2–5) gave the expected products.
1
The structures of the products were confirmed by m.p., microanalysis, H-
NMR-spectral, IR-spectral, and mass-spectral data. The mass spectra showed the
+
correct M peaks and peaks of the fragments. Compound 3a is taken as an example
to describe the general fragmentation mechanism of the thiazole ring, which is
proposed in Scheme 2.
In conclusion, the present study provides a one-pot procedure for the syn-
thesis of 2-mercaptothiazoles, which has the advantages of avoiding the use of
lachrymatory and toxic α-halogenoketones, and higher yields than the method
previously reported (7).
EXPERIMENTAL
All products were recrystallized by EtOH. The m.p. values were measured on
aX4-Datamicroscopicmeltingpointapparatusandareuncorrected. Microanalyses

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HYPERVALENT IODINE. 48
417
Table 1. One-Pot Synthesis of 2-Mercaptothiazoles
Ammonium
Entry
1
Ketones
dithiocarbamate
2-Mercaptothiazoles
Yield (%)
46
N
COCH3
H2N
SH
+
−
S
H
S
1a
1b
H4N S
2
2
2
2
2
2
3a
F
N
COCH3
COCH3
COCH3
COCH3
SH
F
H
S
2
3
4
5
6
3b
57
40
42
43
58
Br
N
SH
3c
Br
H
S
1c
CH3
N
SH
3d
CH3
H
S
1d
Cl
N
SH
3e
Cl
H
S
1e
N
COCH2COCH3
SH
CH3CO
S
1f
3f
CH3
N
CH3COCH2COCH3
SH
3g
CH3CO
S
1
g
7
8
2
2
48
55
CH3CH2
CH3
N
CH3CH2COCH2CH3
1h
SH
3h
S
Ph
N
Ph
H
N
S
2
C H
−
−
SH
e
−HSCN
SH Ph
−S
−
C2H2
PhC
CH
C
C
H
H
S
S
m/e 193
m/e 134
m/e 102
m/e 77
m/e 51
Scheme 2.

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ZHANG AND CHEN
1
were obtained using Carlo-Erba 1106. HNMR spectra were measured on a JEOL
PMX60SI spectrometer using TMS as an interal standard. IR spectra were recorded
with a Perkin Elmer 683 spectrometer. MS spectra were measured on a HP5989B
spectrometer.
Preparation of 2-Mercaptothiazoles 3a–h (General Procedure). To a
solid of HTIB (0.392 g, 1 mmol) was added a solution of ketones
1(a–h, 1 mmol) in dry acetonitrile (10 mL). After the addition was completed,
refluxing was continued for 45 min (suspended solution changes clear). Then wa-
ter (10 mL) and ammonium dithiocarbamate (0.22 g, 2 mmol) were added to it. The
mixture was refluxed for 2.5 hr. Diluting with water (10 mL) and HCl (1 mL), the
solution was extracted with diethyl ether (10 mL × 2). The extracts were dried with
Na2SO4 and the solvent was distilled off in vacuo. The residue was recrystallized
using ethanol to give pure compound.
◦ ◦
-Mercapto-4-Phenylthiazole (3a): m.p. 170–172 C (lit. (9) 172–173 C);
2
−1
−1
−1
−1
IR (KBr): 3100 cm (m, sharp), 2530 cm (vw), 1490 cm (s), 1460 cm
−
1
1
(
(
s), 1060 cm (vs); H NMR (CD3COCD3-d6) δ 7.20–8.20 (1H, m), 7.20–7.62
+
.
5H, m), 6.90 (1H, s). MS: 193 (M , 100), 134 (55.80), 102 (7.16), 89 (16.42),
7
7 (7.75), 51 (7.03).
◦
4
-(p-Fluorophenyl)-2-Mercaptothiazole (3b): m.p. 190–192 C; IR (KBr):
− −1 −1 −1
1
3
1
6
120 cm (m, sharpen), 2580 cm (vw), 1510 cm (s), 1450 cm (s),
060 cm (vs); H NMR (CD3COCD3-d6) δ 7.92 (1H, s), 7.22–7.88 (4H,m),
−1
1
+.
.98 (1H, s); MS: 211 (M , 100), 152 (60.20), 134 (13.23), 133 (10.89), 102
(
2.77), 89 (20.66), Anal. calcd for C9H6FNS2 : C, 51.17; H, 2.86; N, 6.63. Found:
C, 51.93; H, 2.48; N, 6.71.
-(p-Bromophenyl)-2-Mercaptothiazole (3c): m.p. 219–221 C (lit. (15)
◦
4
◦
−1
−1
−1
2
20–222 C); IR (KBr): 3100 cm (m, sharpen), 2600 cm (w), 1530 cm
− −1
1
1
(
s), 1375 cm (s), 1050 cm (vs); H NMR (CD3COCD3-d6) δ 8.0 (1H, s),
+
.
7
(
.47–7.95 (4H, m), 7.15 (1H, s); MS: 271 (M , 34.11), 273 (M + 2, 36.45), 212
4.73), 214 (4.71), 193 (100), 134 (54.40), 102 (5.50), 89 (20.56).
-Mercapto-4-(p-Methylphenyl)thiazole (3d): m.p. 188–190 C (lit. (15)
◦
2
◦
−1
−1
−1
−1
1
90 C); IR (KBr): 3110 cm (m, sharp), 2980 cm , 2950 cm (s), 2610 cm
−1
−1
−1
1
(
vw), 1545 cm (s), 1455 cm (s), 1060 cm (vs); H NMR (CD3COCD3-d6)
+
·
δ 8.02 (1H, s), 7.18–7.66 (4H, m), 7.03 (1H, s), 2.20 (3H, s); MS: 207 (M , 100),
1
92 (11.88), 134 (31.67), 102 (3.20), 89 (25.12).
◦
4
-(p-Chlorophenyl)-2-Mercaptothiazole (3e): m.p. 208–210 C (lit. (15)
◦ −1 −1 −1
2
1
7
1
10–212 C); IR (KBr): 3105 cm (m, sharp), 2540 cm (vw), 1470 cm (s),
−1
−1
1
355 cm (s), 1070 cm vs); H NMR (CD3COCD3-d6) δ 7.92 (1H, s), 7.45–
+
.
.85 (4H, m), 6.85 (1H, s); MS: 229 (M+2, 44.73), 227 (M , 100), 170 (13.97),
69 (7.94), 168 (33.39), 134 (20.08), 133 (20.33), 102 (3.09), 89 (21.69).
◦
5
-Acetyl-2-Mercapto-4-Phenylthiazole (3f): m.p. 148–150 C; IR (KBr):
− −1 −1 −1 −1
1
2980 cm (s), 2685 cm (vw), 1665 cm (vs), 1580 cm (s), 1475 cm (s),

ORDER
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HYPERVALENT IODINE. 48
419
355 cm 1 (s), 1085 cm (s), H NMR (CD3COCD3-d6) δ 7.80 (1H, s), 6.60–7.60
−
−1
1
1
(
+
.
4H, m), 2.72 (3H, s); MS: 235 (M , 100), 220 (59.32), 192 (21.23), 43 (77.11)
Anal. calcd for C11H9NOS2: C, 56.15; H, 3.86; N, 5.95. Found: C, 55.89; H, 3.57;
N, 6.02.
◦
5-Acetyl-2-Mercapto-4-Methylthiazole (3g): m.p. 209–211 C (lit. (21)
◦
−1
−1
−1
−1
210–211 C);IR(KBr):2990cm (s), 2620cm (vw), 1660cm (vs), 1460cm
− −1
1
1
(
s), 1355 cm (s), 1090 cm (s); H NMR (CD3COCD3-d6) δ 4.61 (1H, s),
+
.
2.55 ((3H, s), 2.33 (3H, s); MS: 173 (M , 100), 158 (51.65), 130 (19.19), 43
(
86.39).
-Ethyl-2-Mercapto-5-Methylthiazole (3h): m.p. 178–180 C; IR (KBr):
◦
4
−1
−1
−1
−1
−1
2
970–2940 cm (s), 2650 cm (vw), 1495 cm (s), 1390 cm (s), 1035 cm
1
(
vs); H NMR (CD3COCD3-d6) δ 3.10 (1H, s), 2.45 (2H, q), 2.04 (3H, s), 1.10
+
(
3H, t); MS: 159 (M , 100), 144 (34.23), 100 (8.99), 85 (26.80), 53 (2.71), Anal.
calcd for C6H9NS2: C, 45.25; H, 5.69; N, 8.79. Found: C, 45.52; H, 5.34; N,
8.86.
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Received in Japan January 6, 2000

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