866
E.E. Emelina et al. / Journal of Fluorine Chemistry 130 (2009) 861–869
resultant residue after removal of the solvent under reduced
pressure.
4.1.8. 3-(4-Chlorophenyl)-8-(trifluoromethyl)-6,7-dihydro-5H-
1,4,8a-triaza-s-indacene (4d)
Yield 87%; yellow solid; mp 210–212 8C. 1H NMR (CDCl3):
d 2.29
4.1.2. 1-(2-Ethoxycyclopent-1-enyl)-2,2,2-trifluoroethanone (3a)
(2H, qui, JHH = 7.5 Hz, H-6), 3.12 (2H, t, JHH = 7.5 Hz, H-5), 3.24 (2H,
tq, JHH = 7.5, 5JFH = 2.6 Hz, H-7), 7.38–7.95 (4H, m, C6H4), 8.37 (1H,
Yield 92%; bp 137 8C (8 Torr). 1H NMR (CDCl3):
d 1.35 (3H, t,
JHH = 7 Hz, CH3), 2.27 (2H, qui, JHH = 7.5 Hz, CH2), 3.08 (2H, t,
JHH = 7.5 Hz, CH2), 3.24 (2H, tq, CH2), 4.27 (2H, q, JHH = 7 Hz, OCH2).
s, H-2). 13C NMR (CDCl3): 23.39 (C-6), 28.59 (q, 4JFH = 2.7 Hz, C-7),
d
33.86 (C-5), 109.25 (C-3), 120.30 (q, 1JCF = 275.5, 8-CF3), 123.19 (q,
3JCF = 1.7 Hz, C-7a), 128.50 (q, 2JCF = 36.5 Hz, C-8), 142.13 (C-2),
145.27 (C-3a), 169.41 (C-4a), 127.46, 128.70, 129.84, 131.97 (Ar).
13C NMR (CDCl3): 14.90 (CH3), 23.90 (C-3), 29.10 (q, 4JCF = 2.9 Hz,
d
C-4), 34.24 (C-5), 67.82 (OCH2), 117.50 (q, 1JCF = 275.5, CF3), 95.67
(C-1), 172.41 (C-3), 176.63 (C55O). Anal. Calcd. for C9H11F3O2: C,
51.93; H, 5.33. Found: C, 51.75; H, 5.45.
19F NMR (CDCl3):
d
ꢁ60.96 (t, 5JFH = 2.6 Hz, CF3-8). Anal. Calcd. for
C16H11ClF3N3: C, 56.90; H, 3.28. Found: C, 56.55; H, 3.40.
4.1.3. 1-(2-Ethoxycyclohex-1-enyl)-2,2,2-trifluoroethanone (3b)
4.1.9. 2-Methyl-8-(trifluoromethyl)-6,7-dihydro-5H-1,4,8a-triaza-s-
indacene-3-carbonitrile (4e)
Yield 85%; bp 145 8C (10 Torr). 1H NMR (CDCl3):
d 1.37 (3H, t,
JHH = 7 Hz, CH3), 1.92, 3.10 (8H, m, 4CH2), 4.27 (2H, q, JHH = 7 Hz,
Yield 90%; yellow solid; mp 164 8C. 1H NMR (DMSO-
CH2). 13C NMR (CDCl3),
24.99 (q, JCF = 3.8 Hz, C-3), 24.78 (C-6), 67.82 (OCH2), 117.45 (q,
1JCF = 275.5 Hz, CF3), 92.67 (C-1), 174.41 (C-3), 179.63 (C55O). Anal.
Calcd for C10H13F3O2: C, 54.05; H, 5.90. Found: C, 53.90; H, 6.00.
d
, ppm: 14.64 (CH3), 21.99, 22.72 (C-4, C-5),
d6:CCl4 = 1:2, v/v): d 2.56 (s, 3H, CH3), 2.30 (2H, qui, JHH = 7.5 Hz,
H-6), 3.11 (2H, t, JHH = 7.5 Hz, H-5), 3.25 (2H, tq, JHH = 7.5,
4
5JFH = 2.6 Hz, H-7). 13C NMR (DMSO-d6:CCl4 = 1:2, v/v):
d 12.99
4
(CH3), 22.76 (C-6), 28.13 (q, JFH = 2.1 Hz, C-7), 33.43 (C-5), 81.45
(C-3), 112.02 (CN), 119.58 (q, 1JCF = 276.4 Hz, 8-CF3), 127.49 (q,
4.1.4. General procedure for preparation of 8-trifluoromethyl-6,7-
dihydro-5H-1,4,8a-triaza-s-indacene (4a–h) and 9-(trifluoromethyl)-
5,6,7,8-tetrahydropyrazolo[5,1-b]quinazolines (6a–h)
2JCF = 38.9 Hz, C-8), 150.44 (C-3a), 156.45 (C-2), 173.92 (C-4a). 19
F
5
NMR (CDCl3):
C
d
ꢁ60.44 (t, JFH = 2.6 Hz, CF3-8). Anal. Calcd. for
12H9F3N4: C, 54.14; H, 3.41. Found: C, 54.00; H, 3.62.
The mixture of 5(3)-aminopyrazole 1a–h and 1-(2-ethoxycy-
cloalk-1-enyl)-2,2,2-trifluoroethanone (2a,b) (5.5 mmol) in acet-
onitrile (10 ml) or chloroform (10 ml) was stirred at room
temperature for 1 h, whereupon refluxed for 1 h. After removal
of the solvent under reduced pressure, the resultant solid was
recrystallized from boiling ethanol.
4.1.10. 2-Methyl-3-phenyl-8-(trifluoromethyl)-6,7-dihydro-5H-
1,4,8a-triaza-s-indacene (4f)
Yield 90%; yellow solid; mp 151–153 8C. 1H NMR (CDCl3):
d
2.26
(2H, qui, JHH = 7.5 Hz, H-6), 3.07 (2H, t, JHH = 7.5 Hz, H-5), 3.24 (2H,
tq, JHH = 7.5, 5JFH = 2.8 Hz, H-7), 2.66 (3H, s, CH3), 7.31–7.70 (5H, m,
Ph). 13C NMR (CDCl3):
d
14.13 (CH3), 23.39 (C-6), 28.48 (q, 4JCF
4.1.5. 2-Methyl-8-trifluoromethyl-6,7-dihydro-5H-1,4,8a-triaza-s-
2.7 Hz, C-7), 33.80 (C-5), 109.33 (C-3), 120.53 (q, 1JCF = 274.7 Hz, 8-
CF3), 122.57 (C-7a), 128.60 (q, 2JCF = 36.5 Hz, C-8), 146.61 (C-3a),
indacene (4a)
Yield 93%; pale yellow solid, mp 89 8C. 1H NMR (CDCl3):
d
2.24
152.40 (C-2), 168.63 (C-4a), 126.46, 128.44, 128.93, 131.65 (Ph). 19
F
(2H, qui, JHH = 7.6 Hz, H-6), 2.53 (3H, s, CH3), 3.03 (2H, t,
NMR(CDCl3):
d
ꢁ60.91(t,5JFH = 2.7 Hz,CF3-8).HRMS(ESI):m/zcalcd
5
JHH = 7.6 Hz, H-5), 3.20 (2H, tq, JHH = 7.6 Hz, JFH = 2.7 Hz, H-7),
for C17H15F3N3 (M+H)+: 318.1218; found 318.1186 (100%). Anal.
Calcd. for C17H14F3N3: C, 64.35; H, 4.45. Found: C, 64.40; H, 4.50.
6.43 (1H, s, H-3). 13C NMR (CDCl3):
d
14.64 (CH3), 23.32 (C-6), 28.48
4
1
(q, JCF 2.7, C-7), 33.63 (C-5), 95.83 (C-3), 120.50 (q, JCF 274.7, 8-
CF3), 121.37 (C-7a), 128.15 (q, 2JCF 36.8, C-8), 149.90 (C-3a), 154.90
4.1.11. 2-Methyl-3-(4-chlorophenyl)-8-(trifluoromethyl)-6,7-
(C-2), 168.32 (C-4a). 19F NMR (CDCl3):
d
ꢁ60.95 (t, JFH = 2.7 Hz,
dihydro-5H-1,4,8a-triaza-s-indacene (4g)
5
CF3-8). Anal. Calcd for C11H10F3N3: C, 54.77; H, 4.18. Found: C,
54.60; H, 4.32.
Yield 88%; yellow solid; mp 210 8C. 1H NMR (CDCl3):
d 2.26 (2H,
qui, JHH = 7.5 Hz, H-6), 2.63 (3H, s, CH3), 3.07 (2H, t, JHH = 7.5 Hz, H-
5), 3.24 (2H, tq, JHH = 7.5 Hz, 5JFH = 2.7 Hz, H-7), 7.43–7.63 (4H, m,
4.1.6. 2-(4-Methylphenyl)-8-trifluoromethyl-6,7-dihydro-5H-1,4,8a-
triaza-s-indacene (4b)
Ar). 13C NMR (CDCl3):
d 14.68 (CH3), 23.93 (C-6), 29.03 (q,
4JCF = 2.7 Hz, C-7), 34.35 (C-5), 108.67 (C-3), 120.99 (q,
1JCF = 275.8 Hz, 8-CF3), 122.81 (C-7a), 128.64 (q, 2JCF = 37.0 Hz,
Yield 88%; greenish-yellow solid; mp 199 8C. 1H NMR
(CDCl3:DMSO-d6 = 1:1, v/v):
d
2.28 (2H, qui, JHH = 7.7 Hz, H-6),
C-8), 147.11 (C-3a), 152.76 (C-2), 169.50 (C-4a), 129.15, 130.61,
5
2.42 (3H, s, CH3), 3.08 (2H, t, JHH = 7.7 Hz, H-5), 3.20 (2H, tq,
JHH = 7.7 Hz, 5JFH 2.8, H-7), 6.92 (1H, s, H-3), 7.26–7.92 (4H, m, Ar).
130.73, 132.81 (Ar). 19F NMR (CDCl3):
d
ꢁ60.89 (t, JFH = 2.7 Hz,
CF3-8). HRMS (ESI): m/z calcd for C17H14ClF3N3 (M+H)+: 352.0828;
found 352.0717 (100%). Anal. Calcd. for C17H13ClF3N3: C, 58.05; H,
3.73. Found: C, 57.80; H, 3.87.
13C NMR (CDCl3):
d
21.23 (CH3), 23.28 (C-6), 28.55 (q, 4JCF = 2.7 Hz,
1
C-7), 33.65 (C-5), 92.72 (C-3), 120.48 (q, JCF = 275.3 Hz, 8-CF3),
2
122.07 (C-7a), 128.47 (q, JCF = 37.6 Hz, C-8), 150.27 (C-3a), 155.99
(C-2), 168.51 (C-4a), 126.34, 129.29, 129.67, 138.87 (Ar). Anal.
Calcd. for C17H14F3N3: C, 64.35; H, 4.45. Found: C, 64.15; H, 4.55.
4.1.12. 8-(Trifluoromethyl)-6,7-dihydro-5H-1,4,8a-triaza-s-
indacene-3-carbonitrile (4h)
Yield 89%; yellow solid; mp 176 8C. 1H NMR (CDCl3):
d
2.35 (2H,
4.1.7. 2-(4-Chlorophenyl)-8-trifluoromethyl-6,7-dihydro-5H-1,4,8a-
qui, JHH = 7.5 Hz, H-6), 3.19 (2H, t, JHH = 7.5 Hz, H-5), 3.30 (2H, tq,
5
triaza-s-indacene (4c)
JHH = 7.5, JFH = 2.8 Hz, H-7), 8.34 (s, 1H, H-2). 13C NMR (CDCl3):
d
Yield 90%; yellow solid; mp 205 8C. 1H NMR (CDCl3):
d
2.28 (2H,
23.22 (C-6), 28.57 (q, 4JCF = 2.7 Hz, C-7), 34.02 (C-5), 83.05 (C-3),
111.97 (CN), 119.78 (q, 1JCF = 275.8 Hz, 8-CF3), 125.92 (C-7a), 129.58
(q, 2JCF = 37.0 Hz, C-8), 146.56 (C-3a), 150.51 (C-2), 174.28 (C-4a).
qui, JHH = 7.5 Hz, H-6), 3.08 (2H, t, JHH = 7.5 Hz, H-5), 3.24 (2H, tq,
5
JHH = 7.5, JFH = 2.7 Hz, H-7), 6.91 (1H, s, H-3), 7.42–7.90 (4H, m,
Ar). 13C NMR (CDCl3):
d
23.32 (q, 4JCF = 1.1 Hz, C-6), 28.62 (q,
4JCF = 2.9 Hz, C-7), 33.73 (C-5), 93.05 (C-3), 120.42 (q,
1JCF = 276.1 Hz, 8-CF3), 122.60 (q, 3JCF 2.2 Hz, C-7a), 128.61 (q,
2JCF = 37.5 Hz, C-8), 150.35 (C-3a), 154.72 (C-2), 168.95 (C-4a),
4.1.13. 2-Methyl-9-(trifluoromethyl)-5,6,7,8-
tetrahydropyrazolo[5,1-b]quinazoline (6a)
Yield 87%; yellow solid; mp 87 8C. 1H NMR (CDCl3):
d
1.85, 3.04
(8H, m, 4CH2), 2.52 (3H, s, CH3), 6.40 (1H, s, H-3). 13C NMR (CDCl3):
14.59 (CH3), 21.41, 22.12 (C-6, C-7), 24.38 (q, 5JCF = 3.1 Hz, C-8),
33.93 (C-5), 95.13 (C-3), 117.07 (C-8a), 121.12 (q, 1JCF = 277.9 Hz,
127.72, 128.78, 131.02, 134.78 (Ar). 19F NMR (CDCl3):
5JFH = 2.7 Hz, CF3-8). Anal. Calcd. for C16H11ClF3N3: C, 56.90; H,
d
ꢁ60.85 (t,
d
3.28. Found: C, 56.65; H, 3.36.