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A.E. Ivanova et al. / Journal of Fluorine Chemistry 195 (2017) 47–56
3
4–8 h. Then the inorganic residue formed was filtered off and the
filtrate was concentrated. Compounds 3a-j and 2a,c,e,f,h-j were
obtained by column chromatography using chloroform as an
eluent. Pyrazoles 3b,d,g were isolated as individual substances.
Pyrazoles 3c,e,h-j were isolated as individual substances by
column chromatography using chloroform–hexane 2: 1 as an
eluent.
Method 2 (for pyrazole 1a). A mixture of pyrazole 1a (0.065 g,
0.3 mmol), MeI (0.085 g, 0.6 mmol), Cs2CO3 (0.196 g, 0.6 mmol) in
Me2CO (15 mL) was refluxed for 8 h. Then the inorganic residue was
filtered off and the filtrate was concentrated. Compounds 3a and 2a
were obtained by column chromatography using chloroform as an
eluent.
Method 3 (for pyrazole 1a). A mixture of pyrazole 1a (0.15 g,
0.71 mmol), Me2SO4 (0.189 g,1.5 mmol), K2CO3 (0.21 g,1.5 mmol) in
MeCN (15 mL) was refluxed for 8 h. Then the inorganic residue was
filtered off and the filtrate was concentrated.
Method 4 (for pyrazole 1a). A mixture of pyrazole 1a (0.15 g,
0.71 mmol), MeI (0.5 g, 3.55 mmol) in MeCN (15 mL) was refluxed
for 8 h. The solvent was removed under reduced pressure.
Method 5 (for pyrazole 1a). A mixture of pyrazole 1a (0.1 g,
0.53 mmol), Me2SO4 (0.189 g, 1.5 mmol) in MeCN (15 mL) was
refluxed for 8 h. The solvent was removed under reduced pressure.
Chloroform (20 mL) was added and the reaction mixture was
washed twice with 5% solution of NaHCO3. The solvent was
removed under reduced pressure.
d
= ꢁ114.2 (m, 2F, CF2), ꢁ85.8 (t, 3F, CF3, JF-F = 2.4 Hz). IR (FTIR):
1178–1198 (C-F) cmꢁ1. Analysis: Calc. for C7H7F5N2: C, 39.26; H,
3.30; N, 13.08; F, 44.36%. Found: C, 39.17; H, 3.23; N, 12.99%.
3-Ethyl-1-methyl-5-(1,1,2,2-tetrafluoroethyl)-1H-pyrazole
(2e). 1H NMR (500 MHz, CDCl3):
d
= 1.26 (t, 3H, Me, 3J = 7.6 Hz), 2.67
(q, 2H, CH2, 3J = 7.6 Hz), 3.97 (s, 3H, Me), 6.00 (tt, 1H, H(CF2)2, JH-
F = 53.7, 3JH-F = 2.6 Hz), 6.39 (s, 1H, H-4). 19F NMR (470 MHz, CDCl3):
2
d
= ꢁ134.6 (td, 2F, H(CF2)2, 2JF-H = 53,7 3JF-F = 5.4 Hz), ꢁ110.4 (m, 2F,
H(CF2)2). MS, m/z (%): 210 [M]+ (67), 195 [M-CH3]+ (100), 159 [M-
HCF2]+ (36), 51 [HCF2]+ (15).
5-Ethyl-1-methyl-3-(1,1,2,2-tetrafluoroethyl)-1H-pyrazole
(3e). Yellow oil; yield 20%; 1H NMR (500 MHz, CDCl3):
d
= 1.26 (t,
3H, Me, 3J = 7.6 Hz), 2.67 (q, 2H, CH2, 3J = 7.6 Hz), 3.97 (s, 3H, Me),
6.00 (tt, 1H, H(CF2)2, 2JH-F = 53.7, 3JH-F = 2.6 Hz), 6.39 (s, 1H, H-4). 19
F
3
2
NMR (470 MHz, CDCl3):
H = 4.4 Hz), ꢁ114.1 (dt, 2F, H(CF2)2, JF-H = 53.6, JF-F = 7.4 Hz). IR
(FTIR): 1476 (C N, C
C), 1110 (C-F) cmꢁ1. Analysis: Calc. for
d
= ꢁ137.4 (td, 2F, H(CF2)2, JF-F = 7.4, JF-
2 3
¼
¼
C8H10F4N2: C, 45.72; H, 4.80; F, 36.16; N, 13.33%. Found: C, 45.65; H,
4.79; N, 13.28%. MS, m/z (%): 210 [M]+ (23), 195 [M-CH3]+ (16), 159
[M-HCF2]+ (100).
5-(Heptafluoropropyl)-1-methyl-3-phenyl-1H-pyrazole (2f). Col-
orless oil; yield 60%; 1H NMR (500 MHz, CDCl3):
d
= 4.04 (s, 3H,
, Hm,p, Ph), 7.77-7.79 (m, 2
= ꢁ126.8 (m, 2F, CF2), ꢁ109.1
Me), 6.9 (s, 1H, H-4), 7.32-7.43 (m, 3
=
d
=,
Ho, Ph). 19F NMR (470 MHz, CDCl3):
3
(m, 2F, CF2), ꢁ81.1 (t, CF3, 3F, JF-F = 9.9 Hz). IR (FTIR): 3030, 3066
(CꢁꢁH), 1439 (C
13H9F7N2: C, 47.86; H, 2.78; F, 40.77; N, 8.59%. Found: C, 47.74; H,
2.79; N, 8.36%.
3-(Heptafluoropropyl)-1-methyl-5-phenyl-1H-pyrazole (3f). Col-
orless oil; yield 32%; 1H NMR (500 MHz, CDCl3):
= 3.95 (s, 3H,
Me), 6.58 (s, 1H, H-4), 7.42-7.51 (m, 5H, Ph). 19F NMR (470 MHz,
¼N, C¼
C), 1184–1233 (C-F) cmꢁ1. Analysis: Calc. for
Method 6. A mixture of pyrazoles 1a-j (1 mmol) and Me2SO4
(0.63 g, 5 mmol) was stirred at 80ꢀE for 8 h. Chloroform (20 mL)
was added and the reaction mixture was washed twice with 5%
solution of NaHCO3. The solvent was removed. Compounds 2a,c,e,f,
h-j and 3c,e,f,h-j were obtained by column chromatography using
chloroform as an eluent. Compound 2a was isolated as individual
substance. Compounds 2c,f,h-j were isolated as individual
substances from the mixture by column chromatography using
chloroform–hexane 2: 1 as an eluent.
C
d
CDCl3):
d
= ꢁ128.0 (m, 2F, CF2), ꢁ111.8 (m, 2F, CF2), ꢁ81.3 (t, CF3, 3F,
3JF-F = 9.6 Hz). Analysis: Calc. for C13H9F7N2: C, 47.86; H, 2.78; F,
40.77; N, 8.59%. Found: C, 47.73; H, 2.56; N, 8.49%.
1,5-Dimethyl-3-(heptafluoropropyl)-1H-pyrazole (3 g). Yellow
oil; yield 55%; spectral data and physicochemical properties were
in accordance with the literature [19].
The yields of compounds 2, 3 and their ratio are given in Tables 1
and 3.
1-Methyl-3-phenyl-5(-trifluoromethyl)-1H-pyrazole (2a). The 1H
and 19F NMR spectral data were in accordance with the literature
[5,23].
1-Methyl-4-[(4-methylphenyl)diazenyl]-5-trifluoromethyl-3-phe-
nyl-1H-pyrazole (2 h). Orange crystals, 69%, mp, 76–78 ꢀC; 1H NMR
(500 MHz, CDCl3):
J = 1.6 MHz, Me-1), 7.28–7.29 (m, 2
m,p, Ph); 7.71–7.73 (m, 2
NMR (470 MHz, CDCl3):
3058 ( -H),1485,1442 (C
for E18=15N4F3: 62.79,
d
= 2.42 (s, 3
=
,
E6=4Me), 4.14 (m, 3H,
, Hm, E6=4); 7.36-7.43 (m, 3H,
, Ho, Ph).19
*,
1-Methyl-5-phenyl-3-(trifluoromethyl)-1H-pyrazole (3a). The 1H
and 19F NMR spectral data were in accordance with the literature
[47].
=
H
=
, Ho, E6=4), 7.82-7.84 (m, 2
= ꢁ58.5 (m, J = 1.6 MHz, CF3). IR (DRA):
N, C
C),1145 (C-F) cmꢁ1. Analysis: Calc.
4.39, N 16.27, F, 16.55%. Found: C, 62.60;
=
F
d
1,5-Dimethyl-3-(trifluoromethyl)-1H-pyrazole (3b). Yield 60%;
spectral data and physicochemical properties were in accordance
with the literature [23,34].
E
¼
¼
=
H, 4.36; N, 16.18%. MS, m/z (%): 344 [M]+ (8), 91 [C7H7]+ (100), 89
[C7H5]+ (15), 77 [C6H5]+ (13), 51 [C4H3]+ (11), 43 [CH3N2]+ (12).
1-Methyl-4-[(4-methylphenyl)diazenyl]-3-trifluoromethyl-5-phe-
nyl-1H-pyrazole (3 h). Yield 55%; spectral data and physicochemical
properties were in accordance with the literature [48].
1-Methyl-5-(pentafluoroethyl)-3-phenyl-1H-pyrazole (2c). Color-
less oil; yield 46%; 1H NMR (500 MHz, CDCl3):
d
= 4.05 (s, 3H, Me),
, Hm,p, Ph), 7.76-7.78 (m, 2 , Ho,
= ꢁ111.5 (br. s, 2F, CF2), ꢁ85.0 (t,
N, C C),
6.89 (s, 1H, H-4), 7.34-7.43 (m, 3
=
=
Ph). 19F NMR (470 MHz, CDCl3):
d
3
CF3, 3F, JF-F = 2.9 Hz). IR (FTIR): 3069 (CꢁꢁH), 1439 (C
¼
¼
1,3-Dimethyl-4-[(4-methylphenyl)diazenyl]-5-trifluoromethyl-
1213 (C-F) cmꢁ1. Analysis: Calc. for C12H9F5N2: C, 52.18; H, 3.28; F,
34.39; N, 10.14%. Found: C, 51.99; H, 3.25; N, 10.28%. MS, m/z (%):
276 [M]+ (99), 207 [M-CF3]+ (100), 77 [C6H5]+ (19).
1H-pyrazole (2i). Orange crystals, 48%, mp, 58–60 ꢀC; 1H NMR
(500 MHz, CDCl3):
d
= 2.42 (s, 3
=,
E6=4Me); 2.48 (s, 3
=, c, Me-3);
4.01 (3.90) (m, 3H, J = 1.1, Me-1); 7.27–7.29 (m, 2
=
, Hm, E6=4);
1-Methyl-3-(pentafluoroethyl)-5-phenyl-1H-pyrazole (3c). Color-
7.73–7.75 (m, 2
=
, Ho, E6=4). 19F NMR (470 MHz, CDCl3):
d
= ꢁ58.3
less oil; yield 37% 1H NMR (400 MHz, CDCl3):
d
= 3.94 (s, 3H, Me),
(-59.7) (m, J = 1.1, CF3). IR (DRA): 3036 (CꢁꢁH), 1129 (C-F) cmꢁ1
.
6.58 (s, 1H, H-4), 7.41-7.51 (m, 5H, Ph). 19F NMR (3760 MHz, CDCl3):
Analysis: Calc. for E13=13N4F3: E 55.32; = 4.64; N 19.85; F, 20.19%.
3
d
= ꢁ114.0 (br. s, 2F, CF2), ꢁ85.6 (t, CF3, 3F, JF-F = 2.3 Hz). MS, m/z
Found: C, 55.51; H, 4.71; N, 20.09%. MS, m/z (%): 282 [M]+ (8), 163
[M-C7H7N2]+ (19), 91 [C7H7]+ (100), 51 [C4H3]+ (24), 43 [CH3N2]+
(75)
(%): 276 [M]+ (43), 207 [M-CF3]+ (100), 77 [C6H5]+ (11). IR (FTIR):
3066 (CꢁꢁH), 1469 (C
¼N, C¼
C), 1189–1215 (C-F) cmꢁ1. Analysis:
Calc. for C12H9F5N2: C, 52.18; H, 3.28; F, 34.39; N, 10.14%. Found: C,
52.03; H, 3.25; N, 10.05%. MS, m/z (%): 276 [M]+ (43), 207 [M-CF3]+
(100), 77 [C6H5]+ (11).
1,5-Dimethyl-4-[(4-methylphenyl)diazenyl]-3-trifluoromethyl-
1H-pyrazole (3i). Orange crystals, 63%, mp, 119–120 ꢀC; 1H NMR
(500 MHz, CDCl3):
3); 3.88 (3.68) (s, 3H, Me-1); 7.27–7.29 (m, 2
7.75 (m, 2
, Ho, E6=4). 19F NMR (470 MHz, CDCl3):
(-62.55) (s, CF3). IR (DRA): 3032 (CꢁꢁH), 1425, 1448 (C
d
= 2.42 (2.33) (s, 3
=,
E6=4Me); 2.62 (s, 3
, Hm, E6=4); 7.73–
= ꢁ62.6
N, C C),
=, Me-
1,5-Dimethyl-3-(pentafluoroethyl)-1H-pyrazole (3d). Colorless
=
oil; yield 45%; 1H NMR (400 MHz, CDCl3):
d
= 2.31 (s, 3H, Me-5),
=
d
3.84 (s, 3H, Me-1), 6.30 (s, 1H, H-4). 19F NMR (376 MHz, CDCl3):
¼
¼