K.-J. Kim, K. Kim / Tetrahedron 63 (2007) 5014–5018
5017
separated and dried over MgSO . After removal of solvent in
4
vacuo, the product 11 (1.62 g, 96%) was obtained as a oil and
used in the next step without further purification: dH
4.2.6. 3,4-Diacetyl-1,2,5-thiadiazole (7). Compound 7 was
obtained as an oil from compound 14 according to Swern
oxidation procedure: d (80 MHz, CDCl ) 2.69 (s, 6H);
nmax (neat/cm ) 2924 (w), 2912 (m), 1702 (s), 1593 (m),
1484 (m), 1443 (m), 1401 (m), 1350 (m), 1248 (m), 1142
7
H
3
ꢂ1
(
(
80 MHz, CDCl ) 1.48 (d, J¼7 Hz, 3H), 2.38 (s, 3H), 3.72
3
1
2
d, J¼9 Hz, 1H), 4.74–5.16 (m, 1H), 6.02 (s, 1H).
(m), 1014 (m), 944 (m), 748 (m), 697 (s), 627 (m). Anal.
Calcd for C H N O S: C, 42.34; H, 3.55; N, 16.46; S,
18.84. Found: C, 42.28; H, 3.60; N, 16.42; S, 18.78.
4
.2.3. 3-(1-Acetyloxyethyl)-5-methylisoxazole (12). To
6
6 2 2
a solution of compound 11 (1.59 g, 12.5 mmol) in pyridine
20 mL) was added acetic anhydride (2.16 g, 21.2 mmol)
(
dropwise at room temperature, which was stirred for 12 h.
The reaction mixture was poured on ice (30 g) and extracted
with CH Cl (50 mLꢁ2). The organic layer was separated
4.2.7. 3,4-Diacetyl-1,2,5-thiadiazole dioxime (15). To a
solution of compound 7 (75 mg, 0.44 mmol) at refluxing
methanol (15 mL) was added H NOH$HCl (250 mg,
2
2
2
and dried over MgSO . After removal of solvent in vacuo,
3.62 mmol), which was refluxed for 1 h. After cooled to
room temperature, the reaction mixture was quenched with
water (30 mL) and extracted with ethyl acetate (50 mLꢁ2).
4
the residue was chromatographed on a silica gel column
(
70–230 mesh, 2.5ꢁ5.0 cm). Elution with a mixture of
n-hexane and ethyl acetate (5:1, 100 mL) gave pure 3-(1-
acetyloxyethyl)-5-methylisoxazole (12) (1.74 g, 82%) as
an oil: d (80 MHz, CDCl ) 1.57 (d, J¼7 Hz, 3H), 2.08 (s,
Theorganiclayer was separated and dried over MgSO . After
4
removal of solvent, product 15 (76 mg, 86%) was obtained as
an oil and used in the next reaction without further purifica-
tion: d (80 MHz, CDCl ) 2.26 (s, 6H), 8.33 (br, 2H); n
max
H
3
ꢂ1
(neat/cm )
max
3
H), 2.39 (s, 3H), 5.76–6.18 (m, 2H); n
H
3
ꢂ1
3
136 (w), 2976 (w), 1744 (s), 1603 (m), 1446 (m), 1369
(neat/cm ) 3312 (s), 3024 (w), 2912 (m), 1484 (w), 1443
(m), 1363 (w), 1017 (s), 940 (w), 905 (w), 841 (w), 752
(m), 697 (s).
(
(
w), 1232 (s), 1145 (w), 1062 (w), 1033 (w), 940 (w), 896
w), 851 (w), 800 (w). Anal. Calcd for C H NO : C,
8
11
3
5
6.80; H, 6.55; N, 8.28. Found: C, 56.75; H, 6.58; N, 8.33.
0 0 00
.2.8. 3,3 :4 ,3 -Ter-1,2,5-thiadiazole (16). To a solution of
4
4
(
1
.2.4. 3-Acetyl-4-(1-acetyloxyethyl)-1,2,5-thiadiazole
13). A solution of compound 12 (400 mg, 2.36 mmol) and
(1.14 g, 2.36 mmol) in toluene (30 mL) was heated at
ꢀ
compound 15 (48 mg, 0.24 mmol) in toluene (10 mL) was
added 1 (260 mg, 0.54 mmol), which was heated at
100 C. A spot corresponding to oxime disappeared on
ꢀ
1
00 C for 1 h. The reaction mixture was cooled to room
TLC (R ¼0.05, CCl /CHCl ¼2:1) after 0.5 h and the reac-
f
4
3
temperature when a spot corresponding to compound 12
had disappeared completely on TLC (R ¼0.05, CCl /
tion mixture was cooled to room temperature followed by fil-
tration to remove toluene-insoluble solids. After removal of
toluene in vacuo, the residue was chromatographed on a sil-
ica gel column (70–230 mesh, 1.5ꢁ7.0 cm). Elution with n-
hexane (50 mL) gave a trace amount of sulfur. Elution with
a mixture of CCl and CHCl (1:1, 50 mL) gave pure product
f
4
CHCl ¼2:1). The reaction mixture was filtered to remove
3
the toluene-insoluble solids. After removal of toluene in va-
cuo, the residue was chromatographed on a silica gel column
(70–230 mesh, 2.5ꢁ5.0 cm). Elution with n-hexane (50 mL)
gave a trace amount of sulfur. Elution with a mixture of CCl
and CHCl (2:1, 50 mL) gave unreacted S N (less than
4
4
3
ꢀ
16 (8 mg, 13%) as a pale yellow solid: mp 132–134 C; d
(300 MHz, CDCl ) 9.15 (s, 2H); n
4
H
ꢂ1
(KBr/cm ) 1126
(w), 1040 (w), 886 (s), 832 (m), 768 (m), 527 (m), 499
3
4
3
max
1
(
0 mg). Elution with a mixture of n-hexane and ethyl acetate
4:1, 30 mL) gave pure product 13 (170 mg, 34%) as an oil:
d (80 MHz, CDCl ) 1.61 (d, J¼8 Hz, 3H), 2.07 (s, 3H),
+
(m); MS (m/z) 254 (M , 100), 227 (29.3), 196 (16.8), 168
(4.73), 143 (21.3), 116 (21.4), 84 (8.24), 64 (30.5). Anal.
Calcd for C H N S : C, 28.34; H, 0.79; N, 33.05; S,
37.82. Found: C, 28.35; H, 0.81; N, 33.01; S, 37.77.
H
3
ꢂ1
(neat/cm ) 2992
max
2
.74 (s, 3H), 6.41 (q, J¼8 Hz, 1H); n
6 2 6 3
(
1
(
w), 2912 (w), 1734 (s), 1692 (s), 1596 (w), 1443 (w),
360 (m), 1241 (s), 1084 (s), 1052 (m), 1024 (m), 937
m), 834 (m), 748 (m), 695 (m), 611 (m). Anal. Calcd for
C H N O S: C, 44.85; H, 4.70; N, 13.08; S, 14.97. Found:
4.3. Synthesis of 16 from diethyl acetylenedicarboxylate
8
10 2 3
C, 44.89; H, 4.73; N, 13.02; S, 15.02.
4.3.1. 3,4-Diethoxycarbonyl-1,2,5-thiadiazole (18). A
mixture of compound 17 (1.65 g, 9.70 mmol) and S N
4
4
4
.2.5. 3-Acetyl-4-(1-hydroxyethyl)-1,2,5-thiadiazole (14).
(920 mg, 5.00 mmol) in toluene (40 mL) was heated at re-
flux for 6 h. After removal of solvent in vacuo, the residue
was chromatographed on a silica gel column (70–230
mesh, 2.5ꢁ10 cm). Elution with n-hexane gave a mixture
of sulfur and a trace amount of 3,5-diethoxycarbonyl-
1,2,4-thiadiazole. Elution with a mixture of n-hexane and
ethyl acetate (15:1) gave 4,5-diethoxycarbonyl-1,3,6,2,7-tri-
thiadiazine (186 mg, 7%) and 4-ethoxycarbonyl-1,3,6,2,5,7-
trithiatriazine (93 mg, 4%). Further elution with the same
To a solution of compound 13 (170 mg, 0.79 mmol) in meth-
anol (10 mL) was added NaOH (40 mg, 1.00 mmol) at room
temperature, which was stirred for 0.5 h. After quenched
with saturated NH Cl solution (50 mL), the reaction mixture
4
was extracted with ethyl acetate (50 mLꢁ2). The organic
layer was separated and dried over MgSO . After removal
4
of solvent, the residue was chromatographed on a silica
gel column (70–230 mesh, 1.5ꢁ10 cm). Elution with a mix-
ture of n-hexane and ethyl acetate (5:1, 50 mL) gave pure
product 14 (120 mg, 88%) as an oil: d (80 MHz, CDCl )
8
solvent (10:1) gave pure product 18 (1.23 g, 55%).
H
3
1
5
.62 (d, J¼7 Hz, 3H), 2.80 (s, 3H), 4.31 (br, 1H), 5.09–
4.3.2. 3-Acetyl-4-ethoxycarbonyl-1,2,5-thiadiazole (19).
To a solution of compound 18 (500 mg, 2.17 mmol) in ether
ꢂ1
.47 (m, 1H); n
(neat/cm ) 3456 (s), 3024 (w), 2912
max
(
1
m), 1686 (s), 1593 (w), 1484 (w), 1443 (m), 1056 (w),
020 (w), 953 (w), 899 (w), 848 (w), 752 (s), 697 (s).
Anal. Calcd for C H N O S: C, 41.85; H, 4.68; N, 16.27;
(15 mL, dried over sodium) was added CH MgI (801 mg,
3
4.82 mmol) dropwise at ꢂ78 C under nitrogen atmosphere.
ꢀ
The reaction mixture turned to deep yellow color and was
stirred for 10 min after addition. After warmed to 0 C, the
6
8 2 2
ꢀ
S, 18.62. Found: C, 41.88; H, 4.70; N, 16.21; S, 18.69.