156
S.L. Jeon et al. / Journal of Fluorine Chemistry 128 (2007) 153–157
are given in Hertz. Infrared spectra were determined on a
Mattson Genesis series FT High Resolution Spectrophot-
ometer. Mass spectra were obtained by using GC/MS-Qp1000-
Shimadzu (EI, 70 eV). Melting points were determined in open
capillary tubes and are unconnected.
Anal. Calcd. for C17H10ClF3N2: C, 61.00; H, 3.01. Found: C,
60.87; H, 2.98.
5.3. 4-Trifluoromethyl-2,5,6-triphenylpyrimidine (4a)
Commercially available reagents were purchased from
Aldrich, Lancaster, Tokyo Kasei and Fluorochem. All solvents
were dried by general purification method. Flash chromato-
graphy was performed on 40–60 mm silica gel (230–400 mesh).
A 2 mL microwave reactor was charged with 3c (0.033 g,
0.1 mmol), Pd(PPh3)4 (5 mol%) and 1.5 mL of dry CH3CN.
After bubbling with air gas, phenylstannane (0.048 g,
0.13 mmol) was added into the reactor. The reactor was heated
at 180 8C for 1 h. After quenching with 10% KF solution at
room temperature, the reaction mixture was extracted with
CH2Cl2 twice. The CH2Cl2 solution was dried over anhydrous
MgSO4 and chromatographed on SiO2 column. Elution with a
mixture of hexane and ethyl acetate (9:1) provided 0.035 g of
4a in 93% yield. 4a: mp 127–128 8C: 1H NMR (CDCl3) d 8.68–
8.59 (m, 2H), 7.57–7.49 (m, 3H), 7.42–7.17 (m, 10H); 19F
NMR (CDCl3, internal standard CFCl3) d À63.30 (s, 3F); MS,
m/z (relative intensity) 376 (M+, 51), 375 (100), 355 (8), 168
(13), 151 (12), 77 (20); IR (KBr) 3062, 2929, 1554, 1402, 1196,
1144 cmÀ1. Anal. Calcd. for C23H15F3N2: C, 73.40; H, 4.02.
Found: C, 73.25; H, 4.08.
5. Representative experimental procedures
5.1. 2,3-Dichloro-4,4,4-trifluoro-1-phenyl-2-buten-1-one
(1a)
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with 3,3,3-trifluoropropyne
(1.128 g, 12.0 mmol) and THF at À78 8C and then n-BuLi
(12.0 mmol) was added. After the reaction mixture was stirring
at À78 8C for 30 min, N-methoxy-N-methylbenzamide
(1.815 g, 11.0 mmol) was added into the mixture at À78 8C
and then slowly warmed to 0 8C, followed by quenching with
trifluoromethanesulfonyl chloride (7.37 g, 44.0 mmol). The
reaction mixture was extracted with diethyl ether twice. The
diethyl ether solution was dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with a mixture of
hexane and ethyl acetate (19:1) provided 1.909 g of 1a (E/
Z = 37/63) in 65% yield. 1a: oil: 1H NMR (CDCl3) d 7.97–7.87
(m, 2H), 7.75–7.65 (m, 1H), 7.60–7.50 (m, 2H): 19F NMR
(CDCl3, internal standard CFCl3) d À63.43 (s, 3F, E-isomer),
À62.86 (s, 3F, Z-isomer); MS, m/z (relative intensity) 270
(M+ + 2, 1), 268 (M+, 2), 217 (10), 105 (100), 77 (71), 69 (35);
5.4. 4-Chloro-3-trifluoromethyl-N-methyl-5-
phenylpyrazole (6b)
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to
an argon source was charged with 1a (0.135 g, 0.5 mmol) and
1,4-dioxane. Methylhydrazine (0.051 g, 1.1 mmol) was added
into the mixture and then the reaction was stirred at room
temperature for 5 h. After quenching with water, the reaction
mixture was extracted with diethyl ether twice. The diethyl
ether solution was dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with a mixture
of hexane and ethyl acetate (1:2) provided 0.137 g of 6b in
IR (neat) 3069, 1691, 1598, 1312, 1255, 1195, 1079 cmÀ1
.
Anal. Calcd. for C10H5Cl2F3O: C, 44.64; H, 1.87. Found: C,
44.55; H, 1.85.
1
95% yield. 6b: oil: H NMR (CDCl3) d 7.86–7.81 (m, 2H),
7.48–7.36 (m, 3H), 4.04 (s, 3H); 19F NMR (CDCl3, internal
standard CFCl3) d À59.46 (s, 3F); MS, m/z (relative intensity)
262 (M+ + 2, 14), 260 (M+, 41), 191 (13), 167 (21), 149 (56),
125 (15), 111 (11), 97 (19), 83 (34), 69 (72), 57 (70), 43 (100);
IR (neat) 3066, 2058, 1444, 1271, 1132, 1089 cmÀ1. Anal.
Calcd. for C11H8ClF3N2: C, 50.07; H, 3.01. Found: C, 49.91;
H, 3.04.
5.2. 5-Chloro-4-trifluoromethyl-2,6-diphenylpyrimidine
(3c)
A 25 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with 1a (0.135 g, 0.5 mmol) and 1,4-
dioxane-CH3CN. Bezamidine generated from the neutraliza-
tion of benzamidineÁHClÁH2O (0.172 g, 1.1 mmol) with
K2CO3 was added into the mixture and then the reaction
was heated to reflux for 12 h. After quenching with water, the
reaction mixture was extracted with diethyl ether twice. The
diethyl ether solution was dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with a mixture of
hexane and ethyl acetate (9:1) provided 0.159 g of 3c (E/
Z = 37/63) in 95% yield. 3c: mp 114–115 8C: 1H NMR
(CDCl3) d 8.55–8.49 (m, 2H), 7.95–7.86 (m, 2H), 7.61–7.44
(m, 6H); 19F NMR (CDCl3, internal standard CFCl3) d À67.91
(s, 3F); MS, m/z (relative intensity) 336 (M+ + 2, 30), 334 (M+,
89), 299 (49), 231 (14), 162 (53), 127 (38), 103 (100), 77 (29);
Acknowledgment
This work was supported by Korea Research Foundation
Grant (KRF-2003-041-C00199) and the Maeji Institute of
Academic Research (2004–2005), Yonsei University.
References
[1] J.F. Liebman, A. Greenberg, W.R. Dolbier Jr., Fluorine-Containing
Molecules, VCH, New York, 1988.
[2] R.E. Banks, B.E. Smart, J.C. Tatlow, Organofluorine Chemistry – Prin-
ciple and Commercial Applications, Plenum, New York, 1994.
[3] I. Ojima, J.R. McCarthy, J.T. Welch, Biomedical Frontiers of Fluorine
Chemistry, ACS, Washington, DC, 1996.
IR (KBr) 3065, 2926, 1544, 1373, 1226, 1175, 1046 cmÀ1
.