PAPER
Synthesis of Novel N-Thiazolo-1,3-oxathiol-2-imines
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13C NMR (100 MHz, CDCl3): d = 118.0, 126.3, 128.2, 128.4, 128.6,
128.8, 128.9, 129.3, 129.4, 129.4, 129.5, 129.6, 130.1, 132.0, 133.3,
133.4, 135.3, 140.5, 144.8, 165.5, 165.7.
HRMS–TOF (CI): m/z [M + H]+ calcd for C30H19N2OS2Cl2:
557.0315; found: 557.0314.
2-bromo-2-cyclohexyl-1-phenylethanone (1k) with po-
tassium thiocyanate–silica gel afforded 2k in 12% yield
along with recovered starting material (86%). On the oth-
er hand, reaction of 3-chloro-2-butanone (1l) with potas-
sium thiocyanate–silica gel gave thiocyanate 2l in almost
quantitative yield (Table 4, entries 10 and 11).
Anal. Calcd for C30H18N2OS2Cl2: C, 64.63; H, 3.25; N, 5.02; S,
11.50. Found: C, 64.59; H, 3.24; N, 4.85; S, 11.46.
In conclusion, N-thiazolo-1,3-oxathiol-2-imines have
been synthesized via reaction of various a-haloketones
with potassium thiocyanate–silica gel in toluene at 80 °C.
The heterocycles reported herein are important in the con-
text of the potent biological activities typically associated
with compounds incorporating this heterocyclic system.
N-{2-[4-(4-methylphenyl)-5-phenylthiazolo]}-4-phenyl-5-(4-
methylphenyl)oxathiol-2-imine (3c)
Yellow solid; mp 114 °C.
IR (neat): 3029, 1558, 1078, 756, 695 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.32 (3 H, s), 2.34 (3 H, s), 7.04–
7.15 (4 H, m), 7.28–7.46 (12 H, m), 7.48–7.54 (2 H, m).
13C NMR (100 MHz, CDCl3): d = 21.3, 21.4, 116.5, 125.1, 127.3,
127.8, 128.4, 128.7, 128.7, 128.9, 129.0, 129.2, 129.2, 129.4, 129.7,
130.0, 132.1, 132.6, 137.4, 139.6, 141.8, 146.1, 165.5, 166.1.
HRMS–TOF (CI): m/z [M + H]+ calcd for C32H25N2OS2: 517.1408;
found: 517.1413.
Melting points were determined using a Yanako Micro melting
point apparatus. IR spectra were obtained using a Thermo Electron
Nicolet 380 spectrometer. NMR spectra were recorded using a
JEOL JNM-GX400 or a JEOL JNM-ECX400 spectrometer [1H
NMR at 400 MHz using tetramethylsilane (d = 0) as the internal
standard and 13C NMR at 100 MHz using CDCl3 (d = 77.0) as the
internal standard]. High resolution TOF mass spectra were obtained
using an Agilent G1969 LC/MDS TOF spectrometer. Elemental
analysis data were recorded using a Yanako CHN corder MT-5.
Column chromatography was carried out on silica gel 60N (40–50
mm) from Kanto Chemical Co. Inc.
Anal. Calcd for C32H24N2OS2: C, 74.39; H, 4.68; N, 5.42; S, 12.41.
Found: C, 74.73; H, 4.60; N, 5.34; S, 12.53.
N-{2-[4-(4-Methoxyphenyl)-5-phenylthiazolo]}-4-phenyl-5-(4-
methoxyphenyl)oxathiol-2-imine (3d)
Yellow solid; mp 211–212 °C.
Potassium Thiocyanate–Silica Gel
IR (neat): 2931, 1610, 1539, 1254, 1031, 834 cm–1.
Silica gel [25.70 g, Wakogel C-200 (Wako Pure Chemical Ind.
Ltd.)] was added to a soln of KSCN (24.3 g, 250 mmol) in distilled
H2O and the mixture was stirred at r.t. for 0.5 h. The H2O was evap-
orated under reduced pressure at a temperature below 80 °C, and the
residue was dried in vacuo (10 mmHg) at r.t. for 2 h.
1H NMR (400 MHz, CDCl3): d = 3.80 (3 H, s), 3.81 (3 H, s), 6.80–
6.84 (4 H, m), 7.30–7.37 (3 H, m), 7.39–7.45 (9 H, m), 7.53–7.57 (2
H, m).
13C NMR (100 MHz, CDCl3): d = 55.2, 55.3, 113.6, 113.9, 115.2,
120.4, 127.5, 127.6, 127.7, 128.7, 128.9, 128.9, 129.2, 129.4, 129.7,
130.1, 132.7, 141.6, 145.8, 159.0, 160.2, 165.4, 166.0.
N-Thiazolo-1,3-oxathiol-2-imines; General Procedure
A mixture of a-haloketone (1 mmol) and KSCN–SiO2 (5 mmol)
was stirred in toluene (5 mL) at 80 °C for 6 h, after which the sup-
ported reagent was removed by filtration. The filtrate was evaporat-
ed to leave a crude residue which was purified by column
chromatography using hexane–EtOAc (4:1) as eluent.
HRMS–TOF (CI): m/z [M + H]+ calcd for C32H25N2O3S2: 549.1306;
found: 549.1302.
Anal. Calcd for C32H24N2O3S2: C, 70.05; H, 4.41; N, 5.11; S, 11.69.
Found: C, 70.08; H, 4.23; N, 5.25; S, 11.72.
N-{2-[4-(1-Naphthyl)-5-phenylthiazolo]}-5-(1-naphthyl)-4-phe-
nyl-1,3-oxathiol-2-imine (3e)
Yellow solid; mp 186–187 °C.
N-[2-(4,5-Diphenylthiazolo)]-4,5-diphenyl-1,3-oxathiol-2-
imine (3a)
Yellow solid; mp 189–190 °C.
IR (neat): 3054, 2927, 1723, 1558, 1446, 1116, 773, 757 cm–1.
IR (neat): 3058, 1739, 1580, 1090, 1446, 763, 696 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.03–7.16 (10 H, m), 7.41–7.56 (8
H, m), 7.89–7.97 (5 H, m), 8.13 (1 H, d, J = 8.3 Hz).
1H NMR (400 MHz, CDCl3): d = 7.25–7.44 (16 H, m), 7.49–7.52 (2
H, m), 7.60–7.62 (2 H, m).
13C NMR (100 MHz, CDCl3): d = 120.2, 125.2, 125.3, 125.4, 125.8,
125.9, 126.0, 126.5, 126.6, 127.2, 127.3, 128.0, 128.2, 128.4, 128.4,
128.5, 128.6, 128.6, 128.7, 128.8, 129.3, 129.6, 130.8, 131.4, 131.8,
132.1, 132.2, 133.2, 133.7, 133.9, 141.4, 145.9, 165.4, 166.4.
HRMS–TOF (CI): m/z [M + H]+ calcd for C38H25N2OS2: 589.1408;
found: 589.1413.
13C NMR (100 MHz, CDCl3): d = 117.4, 127.3, 127.6, 127.9, 128.2,
128.5, 128.7, 128.8, 129.1, 129.1, 129.2, 129.3, 129.4, 129.7, 129.8,
132.4, 134.9, 141.5, 146.0, 165.5, 166.0.
HRMS–TOF (CI): m/z [M + H]+ calcd for C30H21N2OS2: 489.1095;
found: 489.1098.
Anal. Calcd for C30H20N2OS2: C, 73.74; H, 4.13; N, 5.73; S, 13.12.
Found: C, 73.82; H, 4.13; N, 5.70; S, 13.03.
Anal. Calcd for C38H24N2OS2: C, 77.52; H, 4.11; N, 4.76; S, 10.89.
Found: C, 77.21; H, 4.24; N, 4.75; S, 10.94.
N-{2-[4-(4-Chlorophenyl)-5-phenylthiazolo]}-4-phenyl-5-(4-
chlorophenyl)oxathiol-2-imine (3b)
Yellow solid; mp 102 °C.
IR (neat): 3058, 2925, 1572, 1475, 1093 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.24 (2 H, d, J = 8.7 Hz), 7.28 (2
H, d, J = 8.7 Hz), 7.33–7.39 (5 H, m), 7.43–7.46 (7 H, m), 7.53 (2
H, d, J = 8.7 Hz).
N-{2-[4-(2-Naphthyl)-5-phenylthiazolo]}-5-(2-naphthyl)-4-phe-
nyl-1,3-oxathiol-2-imine (3f)
Yellow solid; mp 206 °C.
IR (neat): 3052, 1561, 746, 697 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.31–7.34 (3 H, m), 7.42–7.45 (8
H, m), 7.48–7.52 (4 H, m), 7.68–7.82 (7 H, m), 8.12 (1 H, s), 8.18
(1 H, s).
Synthesis 2009, No. 24, 4113–4118 © Thieme Stuttgart · New York