24
T.M. Sokolenko et al. / Journal of Fluorine Chemistry 136 (2012) 20–25
(qd, JCF = 254.1, 34.2 Hz, CF3), 118.2 (qd, JCF = 254.1, 34.2 Hz, CF3),
128.9, 129.7, 130.9, 134.6, 185.5. 19F NMR (188 MHz, CDCl3):
ꢀ81.4 (s, 3 F, CF3), ꢀ81.6 (s, 3 F, CF3), ꢀ148.5 (s, 1 F, CF). GC–MS: m/
z = 383 [M]+. Anal. calcd. for C11H6BrF7O2: C, 34.49; H, 1.58; Br,
20.86; found: C, 34.64; H, 1.71; Br, 20.72.
36.4 Hz, CF), 118.2 (qd, JCF = 290.0, 35.2 Hz, CF3), 127.8, 128.4,
128.7, 129.5, 132.7, 138.7, 161.6. 19F NMR (188 MHz, CDCl3):
ꢀ79.1 (s, 6 F, 2 CF3), ꢀ139.1 (s, 1 F, CF). GC–MS: m/z = 360 [M]+.
Anal. calcd. for C12H7F7N2OS: C, 40.01; H, 1.96; N, 7.78; S, 8.90;
found: C, 40.03; H, 2.06; N, 7.77; S, 8.99.
d
d
4.7. Typical procedure for the cyclization of acetophenones (4a–e)
4.8. Phenyl-[4-phenyl-5-(1,1,2,2-tetrafluoroethoxy)-thiazol-2-yl]-
with thiourea
amine (6)
The mixture of corresponding acetophenone 4a–e (2 mmol)
and thiourea (0.17 g, 2.2 mmol) was stirred at 25 8C for 8 h (48 h for
5e) in the mixture of dioxane (15 mL) and water (5 mL). The
solution of sodium bicarbonate (0.17 g, 2 mmol) in water (10 mL)
was added to the reaction mixture. The precipitate of product was
filtered off, washed with water and dried in vacuum.
The mixture of acetophenone 4a (0.50 g, 1.6 mmol) and N-
phenylthiourea (0.27 g, 1.8 mmol) was stirred at 25 8C for 8 h in the
mixture of dioxane (10 mL) and water (10 mL). The solution of
sodium bicarbonate (0.13 g, 1.6 mmol) in 10 mL of water was
added to the reaction mixture. The precipitate of the product was
filtered off, washed with water and dried in vacuum. Yield 0.56 g
(96%), white powder, mp 107 8C. 1H NMR (400 MHz, CDCl3):
d 5.87
4.7.1. 4-Phenyl-5-(1,1,2,2-tetrafluoroethoxy)-thiazol-2-ylamine (5a)
Yield 0.56 g (96%), white powder, mp 57 8C. 1H NMR (400 MHz,
(tt, JHF = 52.4, 2.4 Hz, 1 =, CHF2), 7.04 (t, JHH = 7.2 Hz, 1 =, Ar=),
7.22–7.38 (m, 8 = + N= + 7 Ar=), 7.78 (d, JHH = 7.6 Hz, 2 =, 2 Ar=).
DMSO-d6):
d
5.86 (tt, JHF = 52.4, 2.4 Hz, 1 =, CHF2), 7.22 (bs, 2 =,
13C NMR (125.75 MHz, DMSO-d6):
d 108.1 (tt, JCF = 249.2, 40.2 Hz,
N=2), 7.32 (t, JHH = 7.6 Hz, 1 =, p-Ar=), 7.41 (t, JHH = 7.6 Hz, 2 =, m-
CHF2), 117.1 (tt, JCF = 274.1, 28.9 Hz, CF2), 117.9, 122.4, 127.7,
128.7, 128.9, 129.1, 129.6, 132.5, 139.2, 141.0, 156.8. 19F NMR
Ar=), 7.76 (d, JHH = 7.6 Hz, 2 =, o-Ar=). 13C NMR (125.75 MHz,
DMSO-d6):
JCF = 274.1, 28.9 Hz, CF2), 127.3, 127.1, 128.3, 128.8, 132.8, 138.7,
161.8. 19F NMR (188 MHz, DMSO-d6):
ꢀ91.1 (s, 2 F, CF2), ꢀ137.1
(d, JFH = 52.2 Hz, 2 F, CHF2). GC–MS: m/z = 292 [M]+. Anal. calcd. for
11H8F4N2OS: C, 45.21; H, 2.76; N, 9.59; S, 10.97; found: C, 45.35;
d
108.1 (tt, JCF = 250.2, 40.2 Hz, CHF2), 117.1 (tt,
(188 MHz, CDCl3):
d
ꢀ90.9 (s, 2 F, CF2), ꢀ137.1 (d, JFH = 52.4 Hz, 2 F,
CHF2). GC–MS: m/z = 368 [M]+. Anal. calcd. for C17H12F4N2OS: C,
55.43; H, 3.28; N, 7.60; S, 8.70; found: C, 55.35; H, 3.35; N, 7.74; S,
8.57.
d
C
H, 2.92; N, 9.49; S, 11.10.
4.9. [3-Methyl-4-phenyl-5-(1,1,2,2-tetrafluoroethoxy)-3H-thiazol-2-
ylidene]-phenyl-amine (7)
4.7.2. 4-Phenyl-5-(2-chloro-1,1,2-trifluoroethoxy)-thiazol-2-ylamine
(5b)
The mixture of acetophenone 4a (0.50 g, 1.6 mmol) and N-
methyl-N0-phenylthiourea (0.30 g, 1.8 mmol) was stirred at 80 8C
for 6 h in the mixture of dioxane (20 mL) and water (10 mL). The
solution of sodium bicarbonate (0.13 g, 1.6 mmol) in 10 mL of
water was added to the reaction mixture. The precipitate of the
product was filtered off, washed with water and dried in vacuum.
Yield 0.61 g (100%), white powder, mp 99 8C. 1H NMR (400 MHz,
Yield 0.61 g (99%), white powder, mp 64 8C. 1H NMR (400 MHz,
DMSO-d6):
d
7.30–7.48 (m, 6 =, NH2 + 3 ArH + CHClF), 7.78 (d,
95.2
JHH = 7.6 Hz, 2 =, o-Ar=). 13C NMR (125.75 MHz, DMSO-d6):
d
(dt, JCF = 247.9, 39.1 Hz, CHClF), 119.0 (td, JCF = 273.5, 25.2 Hz, CF2),
127.6, 127.8, 128.5, 128.8, 132.3, 138.2, 162.0. 19F NMR (188 MHz,
DMSO-d6):
GC–MS: m/z = 310 [M (37Cl)]+, 308 [M (35Cl)]+. Anal. calcd. for
11H8ClF3N2OS: C, 42.80; H, 2.61; Cl, 11.48; N, 9.07; S, 10.39;
d
ꢀ86.2 (s, 2 F, CF2), ꢀ155.3 (d, JFH = 46.2 Hz, 1 F, CHClF).
CDCl3):
7.00–7.09 (m, 3 =, 3 Ar=), 7.29–7.35 (m, 4 =, 4 Ar=), 7.40–7.52 (m,
3 =, 3 Ar=). 13C NMR (125.75 MHz, DMSO-d6):
33.3 (s, E=3), 107.6
d 3.21 (s, 3 =, E=3), 5.57 (tt, JHF = 52.4, 2.4 Hz, 1 =, CHF2),
C
found: C, 43.00; H, 2.80; Cl, 11.49; N, 9.22; S, 10.22.
d
(tt, JCF = 249.2, 40.2 Hz, CHF2), 117.2 (tt, JCF = 274.1, 28.9 Hz, CF2),
4.7.3. 4-Phenyl-5-trifluoromethoxy-thiazol-2-ylamine (5c)
118.9, 121.4, 123.9, 127.2, 129.3, 130.1, 130.2, 130.3, 132.6, 151.2
Yield 0.50 g (96%), white powder, mp 80 8C. 1H NMR (400 MHz,
154.1. 19F NMR (188 MHz, CDCl3):
d
ꢀ90.8 (s, 2 F, CF2), ꢀ137.7 (d,
DMSO-d6):
7.45 (t, JHH = 7.6 Hz, 2 =, m-Ar=), 7.75 (d, JHH = 7.6 Hz, 2 =, o-Ar=).
13C NMR (125.75 MHz, DMSO-d6):
120.9 (q, JCF = 259.0 Hz, CF3),
d
7.33 (bs, 2 =, N=2), 7.35 (t, JHH = 7.6 Hz, 1 =, p-Ar=),
JFH = 52.4 Hz, 2 F, CHF2). GC–MS: m/z = 382 [M]+. Anal. calcd. for
C18H14F4N2OS: C, 56.54; H, 3.69; N, 7.33; S, 8.39; found: C, 56.63; H,
3.75; N, 7.40; S, 8.39.
d
127.6, 127.8, 128.6, 129.0, 132.6, 139.4, 161.8. 19F NMR (188 MHz,
DMSO-d6):
d
ꢀ61.2 (s, CF3). GC–MS: m/z = 260 [M]+. Anal. calcd. for
4.10. Cyclization of acetophenone (4a) with benzoimidazole-2-thione
C
10H7F3N2OS: C, 46.15; H, 2.71; N, 10.76; S, 12.32; found: C, 46.33;
H, 2.88; N, 10.77; S, 12.29.
The mixture of acetophenone 4a (0.50 g, 1.6 mmol) and
benzoimidazole-2-thione (0.24 g, 1.6 mmol) in dioxane (20 mL)
was stirred at 90 8C for 18 h. The solution of sodium bicarbonate
(0.13 g, 1.6 mmol) in 20 mL of water was added to the reaction
mixture. The aqueous phase was extracted with EtOAc (5ꢁ 25 mL).
The combined organic layers were washed with brine (25 mL),
dried with MgSO4 and evaporated to dryness in vacuum to give 8a
(0.61 g, 100%) as a yellowish powder. Alcohol 8a was dissolved in
CH2Cl2 (15 mL) and SOCl2 (0.21 g, 1.8 mmol) was added to the
solution. The reaction mixture was stirred at reflux for 1 h, cooled
to r.t., washed with 5% aqueous sodium bicarbonate solution
(5 mL) and then with water (2ꢁ 5 mL). The organic layer was dried
with MgSO4 and evaporated to dryness in vacuum to give
compound 8b (0.64 g, 100%) as a colorless solid. The solution of
KOH (0.1 g, 1.8 mmol) in 10 mL of ethanol was added to
chlorotiazoline 8b and the mixture was stirred for 1 h at 25 8C.
The solvent was evaporated to dryness in vacuum. Ether (20 mL)
was added to the residue and the organic solution was washed
4.7.4. 4-Phenyl-5-pentafluoroethoxy-thiazol-2-ylamine (5d)
Yield 0.62 g (100%), white powder, mp 90 8C. 1H NMR (400 MHz,
DMSO-d6):
=, m-Ar=), 7.70 (d, JHH = 7.6 Hz,
(125.75 MHz, DMSO-d6): 113.9 (tq, JCF = 275.4, 41.9 Hz, CF2),
116.1 (qt, JCF = 284.9, 43.3 Hz, CF3), 125.6, 127.1, 128.2, 128.4,
d
7.32–7.38 (m, 3 =, p-Ar= + N=2), 7.43 (t, JHH = 7.6 Hz,
2
2
=, o-Ar=). 13C NMR
d
132.1, 139.5, 161.7. 19F NMR (188 MHz, DMSO-d6):
d
ꢀ85.6 (s, 3 F,
CF3), ꢀ90.5 (s, 2 F, CF2). GC–MS: m/z = 310 [M]+. Anal. calcd. for
C
11H7F5N2OS: C, 42.59; H, 2.27; N, 9.03; S, 10.33; found: C, 42.65;
H, 2.32; N, 9.02; S, 10.44.
4.7.5. 4-Phenyl-5-heptafluoroisopropyloxy-thiazol-2-ylamine (5e)
Yield 0.71 g (99%), white powder, mp 98 8C. 1H NMR (400 MHz,
DMSO-d6):
7.42 (t, JHH = 7.4 Hz, 2 =, m-Ar=), 7.71 (d, JHH = 7.4 Hz, 2 =, o-Ar=).
13C NMR (125.75 MHz, DMSO-d6):
102.3 (d sept, JCF = 254.2,
d 7.30 (bs, 2 =, N=2), 7.34 (t, JHH = 7.4 Hz, 1 =, p-Ar=),
d