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HRMS m/z: 283.9677 (Calcd for C10H8Cl2F2OS: 216.0420). IR (neat) cmϪ1
1245.
:
214 Hz), Ϫ30.5—Ϫ30.6 (1F, m), Ϫ32.3—Ϫ32.4 (1F, m). MS m/z (%): 336
(4, Mϩϩ1), 224 (100). HRMS m/z: 336.0820 (Calcd for C13H14F4N3OS:
336.0794). IR (KBr) cmϪ1: 3100. Anal. Calcd for C13H13F4N3OS: C, 46.56;
H, 3.91; N, 12.53. Found: C, 46.15; H, 3.87; N, 12.43.
2-[[[2-(2,4-Difluorophenyl)-2-oxiranyl]difluoromethyl]thio]ethyl acetate
(8l): Colorless oil. Yield 90%. 1H-NMR (CDCl3) d: 2.06 (3H, s), 2.95—3.00
(1H, m), 3.07 (2H, dd, Jϭ1.0, 6.8 Hz), 3.48—3.51 (1H, m), 4.24 (2H, t,
Jϭ6.4 Hz), 6.82—6.88 (1H, m), 6.90—6.96 (1H, m), 7.50—7.56 (1H, m).
19F-NMR (CDCl3) d: Ϫ4.3 (1F, dd, Jϭ10, 211 Hz), Ϫ5.9 (1F, dd, Jϭ5,
211 Hz), Ϫ31.1—Ϫ31.2 (1F, m), Ϫ33.1—Ϫ33.2 (1F, m). MS m/z (%): 324
(0.2, Mϩ), 205 (100). HRMS m/z: 324.0450 (Calcd for C13H12F4O3S:
324.0444). IR (neat) cmϪ1: 1745, 1230.
2-(2,4-Difluorophenyl)-2-[difluoro(phenylthio)methyl]oxirane (8n): Col-
orless oil. Yield 49%. 1H-NMR (CDCl3) d: 3.00—3.03 (1H, m), 3.50—3.52
(1H, m), 6.83—6.86 (1H, m), 6.87—7.00 (1H, m), 7.32—7.38 (3H, m),
7.39—7.44 (1H, m), 7.48—7.61 (2H, m). 19F-NMR (CDCl3) d: Ϫ5.1 (1F,
dd, Jϭ10, 213 Hz), Ϫ6.3 (1F, dd, Jϭ7, 213 Hz), Ϫ31.3—Ϫ31.4 (1F, m),
Ϫ33.0—Ϫ33.2 (1F, m). MS m/z: 314 (0.2, Mϩ), 91 (100). HRMS m/z:
314.0364 (Calcd for C15H10F4OS: 314.0388). IR (neat) cmϪ1: 1270.
2-[Difluoro[(4-methylphenyl)thio]methyl]-2-(2,4-difluorophenyl)oxirane
(8o): Colorless oil. Yield 52%. 1H-NMR (CDCl3) d: 2.35 (3H, s), 3.00—
3.05 (1H, m), 3.45—3.50 (1H, m), 6.82—6.88 (1H, m), 6.90—6.96 (1H, m),
7.16 (2H, d, Jϭ8.3 Hz), 7.44 (2H, d, Jϭ8.3 Hz), 7.54—7.60 (1H, m). 19F-
NMR (CDCl3) d: Ϫ4.5 (1F, dd, Jϭ10, 209 Hz), Ϫ5.5 (1F, dd, Jϭ7, 210 Hz),
Ϫ31.3—Ϫ31.4 (1F, m), Ϫ32.9—Ϫ33.0 (1F, m). MS m/z (%): 328 (74, Mϩ),
169 (100). HRMS m/z: 328.0533 (Calcd for C16H12F4OS: 328.0545). IR
(neat) cmϪ1: 1270.
2-(2,4-Difluorophenyl)-1,1-difluoro-1-propylthio-3-(1H-1,2,4-triazol-1-
yl)-2-propanol (9c): Colorless powder. mp 86.7 °C. Yield 32%. 1H-NMR
(CDCl3) d: 0.97 (3H, t, Jϭ7.3 Hz), 1.61—1.70 (2H, m), 2.80 (2H, t,
Jϭ7.3 Hz), 4.82 (1H, d, Jϭ14.2 Hz), 5.28 (1H, d, Jϭ14.2 Hz), 5.65 (1H, s),
6.70—6.77 (1H, m), 6.83—6.88 (1H, m), 7.70—7.77 (1H, m), 7.82 (1H, s),
8.09 (1H, s). 19F-NMR (CDCl3) d: Ϫ5.4 (1F, dd, Jϭ25, 211 Hz), Ϫ8.7 (1F,
dd, Jϭ16, 211 Hz), Ϫ30.2—Ϫ30.3 (1F, m), Ϫ32.0—Ϫ32.1 (1F, m). MS m/z
(%): 349 (1, Mϩ), 224 (100). HRMS m/z: 349.0887 (Calcd for
C14H15F4N3OS: 349.0871). IR (KBr) cmϪ1
: 3100. Anal. Calcd for
C14H15F4N3OS: C, 48.13; H, 4.33; N, 12.03. Found: C, 8.41; H, 4.34; N,
12.07.
1-(Cyclopropylthio)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-tria-
1
zol-1-yl)-2-propanol (9d): Colorless powder. mp 102.1 °C. Yield 57%. H-
NMR (CDCl3) d: 0.65—0.70 (2H, m), 0.95—1.00 (2H, m), 2.00—2.05 (1H,
m), 4.81 (1H, d, Jϭ14.2 Hz), 5.28 (1H, d, Jϭ14.2 Hz), 5.68 (1H, s), 6.70—
6.75 (1H, m), 6.80—6.85 (1H, m), 7.70—7.75 (1H, m), 7.81 (1H, s), 8.09
(1H, s). 19F-NMR (CDCl3) d: Ϫ7.6 (1F, dd, Jϭ24, 214 Hz), Ϫ10.1 (1F, dd,
Jϭ22, 214 Hz), Ϫ30.6—Ϫ30.7 (1F, m), Ϫ32.3—Ϫ32.4 (1F, m). MS m/z
(%): 347 (4, Mϩ), 224 (100). HRMS m/z: 347.0710 (Calcd for
C14H13F4N3OS: 347.0715). IR (KBr) cmϪ1
: 3100. Anal. Calcd for
C14H13F4N3OS: C, 48.41; H, 3.77; N, 12.10; S, 9.23. Found: C, 48.62; H,
3.82; N, 12.09; S, 9.14.
2-[(Benzylthio)difluoromethyl]-2-(2,4-difluorophenyl)oxirane (8p): Col-
orless oil. Yield 99%. 1H-NMR (CDCl3) d: 2.97—3.00 (1H, m), 3.49—3.50
(1H, m), 4.07 (2H, s), 6.80—6.85 (1H, m), 6.86—6.92 (1H, m), 7.26—7.34
(5H, m), 7.50—7.55 (1H, m). 19F-NMR (CDCl3) d: Ϫ5.2 (1F, dd, Jϭ10,
213 Hz), Ϫ6.3 (1F, dd, Jϭ10, 213 Hz), Ϫ31.2—Ϫ31.3 (1F, m), Ϫ33.0—
Ϫ33.1 (1F, m). MS m/z: 328 (0.3, Mϩ), 91 (100). HRMS m/z: 328.0530
(Calcd for C16H12F4OS: 328.0545). IR (neat) cmϪ1: 1270.
1-(Butylthio)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-1-
yl)-2-propanol (9e): Colorless powder. mp 77.1 °C. Yield 61%. 1H-NMR
(CDCl3) d: 0.90 (3H, t, Jϭ7.3 Hz), 1.36—1.41 (2H, m), 1.57—1.64 (2H,
m), 2.82 (2H, t, Jϭ7.3 Hz), 4.82 (1H, d, Jϭ14.6 Hz), 5.28 (1H, d,
Jϭ14.6 Hz), 5.68 (1H, s), 6.71—6.77 (1H, m), 6.82—6.88 (1H, m), 7.70—
7.77 (1H, m), 7.81 (1H, s), 8.09 (1H, s). 19F-NMR (CDCl3) d: Ϫ5.8 (1F, dd,
Jϭ25, 211 Hz), Ϫ9.0 (1F, dd, Jϭ16, 211 Hz), Ϫ30.4—Ϫ30.6 (1F, m),
Ϫ32.3—Ϫ32.4 (1F, m). MS m/z (%): 364 (1, Mϩϩ1), 224 (100). HRMS
m/z: 364.1014 (Calcd for C15H18F4N3OS: 349.0871). IR (KBr) cmϪ1: 3100.
Anal. Calcd for C15H17F4N3OS: C, 49.58; H, 4.72; N, 11.56; S, 8.82. Found:
C, 49.68; H, 4.77; N, 11.54; S, 8.82.
1-(tert-Butylthio)-2-(2,4-difluorophenyl)-1,1-difluoro-3-(1H-1,2,4-triazol-
1-yl)-2-propanol (9f): Colorless powder. mp 142.7 °C. Yield 42%. 1H-NMR
(CDCl3) d: 1.46 (9H, s), 5.28 (1H, d, Jϭ14.7 Hz), 5.28 (1H, d, Jϭ14.7 Hz),
5.78 (1H, s), 6.70—6.78 (1H, m), 6.81—6.86 (1H, m), 7.68—7.74 (1H,m),
7.77 (1H, s), 8.09 (1H, s). 19F-NMR (CDCl3) d: Ϫ1.9 (1F, dd, Jϭ25,
211 Hz), Ϫ6.7 (1F, dd, Jϭ17, 211 Hz), Ϫ30.1—Ϫ30.2 (1F, m), Ϫ32.6—
Ϫ32.7 (1F, m). MS m/z (%): 363 (0.8, Mϩ), 224 (100). HRMS m/z:
363.1020 (Calcd for C15H17F4N3OS: 363.1028). IR (KBr) cmϪ1: 3100. Anal.
Calcd for C15H17F4N3OS: C, 49.58; H, 4.72; N, 11.56. Found: C, 49.80; H,
4.80; N, 11.70.
2-[Difluoro[(4-methoxybenzyl)thio]methyl]-2-(2,4-difluorophenyl)oxi-
1
rane (8q): Colorless oil. Yield 71%. H-NMR (CDCl3) d: 2.97—3.00 (1H,
m), 3.48—3.50 (1H, m), 3.78 (3H, s), 4.04 (2H, s), 6.80—6.85 (1H, m), 6.83
(2H, d, Jϭ8.8 Hz), 6.86—6.93 (1H, m), 7.22 (2H, d, Jϭ8.8 Hz), 7.45—7.55
(1H, m). 19F-NMR (CDCl3) d: Ϫ5.3 (1F, dd, Jϭ10, 214 Hz), Ϫ6.5 (1F, dd,
Jϭ5, 214 Hz), Ϫ31.3—Ϫ31.4 (1F, m), Ϫ33.1—Ϫ33.2 (1F, m). MS m/z (%):
358 (34, Mϩ), 121 (100). HRMS m/z: 358.0681 (Calcd for C17H14F4O2S:
358.0650). IR (neat) cmϪ1: 1250.
General Procedure for the Synthesis of 1,1-Difluoro-1-(substituted
thio)-3-(1H-1,2,4-triazol-1-yl)-2-propanol (9) 1,2,4-Triazole (2.2 mmol)
and K2CO3 (1.1 mmol) were added to a solution of 8 (2 mmol) in dimethyl-
formamide (DMF) (30 ml). The mixture was warmed at 65 °C for 5 h. After
addition of aqueous NaHCO3, the mixture was extracted with AcOEt. The
organic extract was washed with water and brine, dried over MgSO4, and
evaporated under reduced pressure. The residue was chromatographed on a
silica gel column using CHCl3–MeOH [98 : 2 (v/v)] as a mobile phase to
give 9.
Resolution of (؎)-9 into (؉)-9 and (؊)-9 Compound (Ϯ)-9 (50 mg)
was subjected to preparative HPLC (CHIRALCEL OD with pre-column
CHIRALCEL OD), using n-hexane–2-propanol [3 : 1 (v/v)] as a mobile
phase. The more mobile isomer is (Ϫ)-9 and the less mobile isomer is (ϩ)-
9. Their optical yields are measured by HPLC (CHIRALCEL OD with pre-
column CHIRALCEL OD) using n-hexane–2-propanol [1 : 1 (v/v)] as a mo-
bile phase (flow rate: 0.5 ml/min, column temperature: 21 °C).
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(pentylthio)-3-(1H-1,2,4-triazol-1-
yl)-2-propanol (9g): Colorless powder. mp 59 °C. Yield 58%. 1H-NMR
(CDCl3) d: 0.90 (3H, t, Jϭ7.3 Hz), 1.17—1.80 (6H, m), 2.82 (2H, t,
Jϭ7.3 Hz), 4.82 (1H, d, Jϭ14.6 Hz), 5.28 (1H, d, Jϭ14.6 Hz), 5.68 (1H, s),
6.71—6.77 (1H, m), 6.82—6.88 (1H, m), 7.70—7.77 (1H, m), 7.81 (1H, s),
8.09 (1H, s). 19F-NMR (CDCl3) d: Ϫ5.8 (1F, dd, Jϭ25, 211 Hz), Ϫ9.0 (1F,
dd, Jϭ16, 211 Hz), Ϫ30.4—Ϫ30.6 (1F, m), Ϫ32.3—Ϫ32.4 (1F, m). MS m/z
(%): 378 (1, Mϩϩ1), 224 (100). HRMS m/z: 378.1242 (Calcd for
C16H20F4N3OS: 378.1263). IR (KBr) cmϪ1
: 3100. Anal. Calcd for
2-(2,4-Difluorophenyl)-1,1-difluoro-1-(methylthio)-3-(1H-1,2,4-triazol-1-
yl)-2-propanol (9a): Colorless powder. mp 122.2 °C. Yield 72%. 1H-NMR
(CDCl3) d: 2.27 (3H, s), 4.82 (1H, d, Jϭ14.2 Hz), 5.28 (1H, d, Jϭ14.2 Hz),
5.76 (1H, s), 6.71—6.75 (1H, m), 6.76—6.88 (1H, m), 7.71—7.77 (1H, m),
7.80 (1H, s), 8.09 (1H, s). 19F-NMR (CDCl3) d: Ϫ9.4 (1F, dd, Jϭ25,
211 Hz), Ϫ11.8 (1F, dd, Jϭ15, 211 Hz), Ϫ30.4—Ϫ30.5 (1F, m), Ϫ32.2—
Ϫ32.3 (1F, m). MS m/z (%): 321 (1, Mϩ), 224 (100). HRMS m/z: 321.0546
(Calcd for C12H11F4N3OS: 321.0559). IR (KBr) cmϪ1: 3100.
C16H19F4N3OS: C, 50.78; H, 5.33; N, 11.10; S, 8.47. Found: C, 50.92; H,
5.07; N, 11.13; S, 8.50.
1,1-Difluoro-1-(methylthio)-2-phenyl-3-(1H-1,2,4-triazol-1-yl)-2-
propanol (9h): Colorless powder. mp 135.8 °C. Yield 38%. 1H-NMR
(CDCl3) d: 2.19 (3H, s), 4.82 (1H, d, Jϭ14.7 Hz), 4.87 (1H, d, Jϭ14.7 Hz),
6.03 (1H, s), 7.30—7.35 (3H, m), 7.55—7.58 (2H, m), 7.69 (1H, s), 7.88
(1H, s). 19F-NMR (CDCl3) d: Ϫ8.7 (1F, d, Jϭ211 Hz), Ϫ11.4 (1F, d,
Jϭ211 Hz). MS m/z (%): 285 (5, Mϩ), 188 (100). HRMS m/z: 285.0734
(Calcd for C12H13F2N3OS: 285.0748). IR (KBr) cmϪ1: 3100. Anal. Calcd for
C12H13F2N3OS: C, 50.52; H, 4.58; N, 14.73; S, 11.24. Found: C, 50.70; H,
4.56; N, 14.77; S, 11.34.
1,1-Difluoro-2-(4-fluorophenyl)-1-(methylthio)3-(1H-1,2,4-triazol-1-yl)-
2-propanol (9i): Colorless powder. mp 123.6 °C. Yield 70%. 1H-NMR
(CDCl3) d: 2.23 (3H, s), 4.75 (1H, d, Jϭ14.2 Hz), 4.88 (1H, d, Jϭ14.2 Hz),
5.55 (1H, s), 7.00—7.05 (2H, m), 7.50—7.55 (2H, m), 7.81 (1H, s), 7.92
(1H, s). 19F-NMR (CDCl3) d: Ϫ8.7 (1F, dd, Jϭ7, 214 Hz), Ϫ6.7 (1F, dd,
Jϭ11, 214 Hz), Ϫ35.8 (1F, s). MS m/z (%): 303 (2, Mϩ), 206 (100). HRMS
m/z: 303.0658 (Calcd for C12H12F3N3OS: 303.0653). IR (KBr) cmϪ1: 3100.
(ϩ)-9a: Colorless powder, mp 154—156 °C, e.e. 99.2%, [a]D25: 64.6°
(cϭ0.5, acetone), retention time (min): 9.23.
(Ϫ)-9a: Colorless powder, mp 154—156 °C, e.e. 99.2%, [a]D25: Ϫ65.0°
(cϭ0.5, acetone), retention time (min): 8.80.
2-(2,4-Difluorophenyl)-1-(ethylthio)-1,1-difluoro-3-(1H-1,2,4-triazol-1-
yl)-2-propanol (9b): Colorless powder. mp 110.7 °C. Yield 85%. 1H-NMR
(CDCl3) d: 1.30 (3H, t, Jϭ7.3 Hz), 2.85 (2H, q, Jϭ7.3 Hz), 4.82 (1H, d,
Jϭ14.2 Hz), 5.28 (1H, d, Jϭ14.2 Hz), 5.71 (1H, s), 6.71—6.77 (1H, m),
6.82—6.88 (1H, m), 7.70—7.77 (1H, m), 7.81 (1H, s), 8.09 (1H, s). 19F-
NMR (CDCl3) d: Ϫ5.9 (1F, dd, Jϭ25, 214 Hz), Ϫ9.3 (1F, dd, Jϭ12,