PAPER
Synthesis of 9-Trifluoromethylated [1,2,4]Triazolo[1,5-a]azepine Derivatives
353
IR (neat): 2953, 1517, 1254, 1176, 1143 cm 1.
CF ), 123.5, 129.1, 129.9, 130.3, 131.6, 131.7, 132.2, 137.1, 137.2,
3
1H NMR (CDCl3): = 1.67 2.49 (m, 8 H, 4 CH ), 3.07 (m, Z), 3.46
142.9 (Ar), 160.4, 162.4 (C=N).
2
(
m, E) (1 H, CHCF3).
Anal. Calcd for C H Cl F N Sb: C, 31.13; H, 2.24; N, 5.19.
21
18
9
3
3
Found: C, 31.30; H, 2.29; N, 5.09.
3
c: yield, 92%; dark-red oil.
IR (neat): 2950, 1529, 1252, 1174, 1144 cm 1.
6d: Yield: 90%; white needles (MeOH MeCN, 1:1); mp 224
2
26 °C.
1
H NMR (CDCl3): = 1.72 2.42 (m, 8 H, 4 CH ), 3.09 (m, Z),
2
IR (KBr): 2940, 1558, 1268, 1186 cm 1.
3
.45 (m, E) (1 H, CHCF ), 7.39 8.43 (m, 4 H, 4-NO C H ).
3
2
6
4
1
H NMR (CD CN): = 1.81 2.54 (m, 6 H, 3 CH ), 4.35 (m, 2 H,
3
2
3
d: yield, 94%; yellow oil.
NCH ), 4.52 (m, 1 H, CHCF ), 7.64 7.86 (m, 5 H, C H ), 8.03 (s,
2
3
6
5
IR (neat): 2950, 1769, 1252, 1175 cm 1.
2
H, Cl C H ).
3
6
2
1
H NMR (CDCl3): = 1.43 (t, 3 H, J = 7.2 Hz, CH ), 1.63 2.27 (m,
13
3
C NMR (CD CN): = 24.4, 25.8, 27.3 (CH ), 44.8 (q, J = 29.6
3 2
8
H, 4 CH ), 3.00 (m, Z), 3.18 (m, E) (1 H, CHCF ), 4.46 (q, 2 H,
2
3
Hz, CHCF ), 50.4 (CH N), 125.7 (q, J = 277.7 Hz, CF ), 125.2,
3
2
3
J = 7.2 Hz, OCH2).
129.6, 132.1, 135.5 (C H ), 123.3, 131.0, 131.2, 137.0, 137.3, 143.0
6
5
(
Cl C H ), 160.2, 160.9 (C=N).
3 6 2
Preparation of 9-Trifluoromethyl-6,7,8,9-tetrahydro-5H-
1,2,4]triazolo[1,5-a]azepine Derivatives 6a–j and
the Picrates 8a,b: General Procedure
Anal. Calcd for C H Cl F N Sb: C, 30.17; H, 2.03; N, 5.28.
Found: C, 30.24; H, 2.04; N, 5.15.
2
0
16
9
3
3
[
To a soln of 3 (10 mmol) and the corresponding nitrile (12 mmol)
in anhyd CH Cl (15 mL) was added dropwise a soln of SbCl (3.60
6e: Yield: 90%; white needles (MeOH); mp 192 °C.
IR (KBr): 2943, 1558, 1277, 1180 cm–1.
2
2
5
g, 12 mmol) in CH Cl (10 mL) at a temperature of about 70 °C.
2
2
1
H NMR (CD CN): = 1.81 2.46 (m, 6 H, 3 CH ), 2.69 (s, 3 H,
After stirring at this temperature for 1 h, the mixture was allowed
gradually warm to 30 °C (bath temperature) and stirred additional
3
2
CH ), 4.34 4.41 (m, 3 H, CH N, CHCF ).
3
2
3
3
0 min to make sure that the rearrangement was complete. Precipi-
13
C NMR (CD CN): = 13.6 (CH ), 24.0, 25.3, 27.2 (CH ), 44.6 (q,
3
3
2
tation was induced by careful addition of Et O. The crystalline
2
J = 29.6 Hz, CHCF ), 51.1 (CH N), 125.6 (q, J = 277.7 Hz, CF ),
3
2
3
product was collected by filtration and dried in vacuo (CaCl ). Re-
2
138.3, 141.6, 143.6, 145.1, 147.2, 148.6 (C F ), 160.9, 162.3
6 5
crystallization from appropriate solvent [MeOH MeCN, (1:1),
MeOH, or CH Cl ] provided the analytically pure 9-trifluoro-
(C=N).
2
2
Anal. Calcd for C H Cl F N Sb: C, 25.00; H, 1.68; N, 5.83.
1
5
12
6
8
3
methyl-6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[1,5-a]azepinium
hexachloroantimonates 6a h.
Found: C, 25.17; H, 1.76; N, 5.81.
f: Yield: 97%; white crystals (MeOH MeCN, 1:1); mp 198 °C.
IR (KBr): 2949, 1555, 1276, 1180 cm 1.
1H NMR (CD
CN): = 1.44 (t, J = 7.47, 3 H, CH
6 H, 3 CH ), 2.49 (q, J = 7.47, 2 H, CH Me), 4.34 4.41 (m, 3 H,
CH N, CHCF ).
6
6
a: Yield: 89%; white crystals (MeOH MeCN, 1:1); mp 210
2
12 °C.
IR (KBr): 2948, 1557, 1265, 1181 cm 1.
), 1.82 2.45 (m,
3
3
1
2
2
H NMR (CD CN): = 1.77 2.49 (m, 6 H, 3 CH ), 2.62 (s, 3 H,
3
2
2
3
CH ), 4.27 (m, 2 H, NCH ), 4.45 (m, 1 H, CHCF ), 8.05 (s, 2 H,
3
2
3
13C NMR (CD
44.8 (q, J = 29.6 Hz, CHCF
CN): = 10.8 (CH
), 50.9 (CH
2
), 21.2, 24.0, 25.3, 27.3 (CH
),
2
Cl C H ).
3
3
3
6
2
1
3
3
N), 125.7 (q, J = 277.7 Hz,
C NMR (CD CN): = 13.6 (CH ), 24.5, 25.8, 27.3 (CH ), 44.8 (q,
3
3
2
CF ), 138.4, 141.8, 143.8, 145.2, 147.3, 148.7 (C F ), 161.1, 166.2
3
6 5
J = 29.6 Hz, CHCF ), 50.7 (CH N), 125.7 (q, J = 277.7 Hz, CF ),
3
2
3
(C=N).
1
23.6, 131.8, 137.0, 137.1, 142.9 (Cl C H ), 160.3, 161.4 (C=N).
3 6 2
Anal. Calcd for C H Cl F N Sb: C, 26.16; H, 1.92; N, 5.72.
Found: C, 26.27; H, 2.08; N, 5.77.
1
6
14
6
8
3
Anal. Calcd for C H Cl F N Sb: C, 24.54; H, 1.92; N, 5.72.
Found: C, 24.55; H, 1.99; N, 5.77.
1
5
14
9
3
3
6
g: Yield, 94%; white crystals (CH Cl ); mp 158 160 °C.
2
2
6
1
b: Yield: 87%; white crystals (MeOH MeCN, 1:1); mp 176
78 °C.
IR (KBr): 2949, 1550, 1270, 1189 cm 1.
1H NMR (CD
CN): = 1.91 2.52 (m, 6 H, 3 CH
N, CHCF ), 5.56 (s, 2 H, CH Cl ), 7.67 7.89 (m, 5 H,
IR (KBr): 2946, 1558, 1267, 1183 cm 1.
), 4.42 4.50 (m,
2
3
1
3 H, CH
C H ).
2
3
2
2
H NMR (CD CN): = 1.40 (t, J = 7.6 Hz, 3 H, CH ), 1.77 2.49
3
3
6
5
(m, 6 H, 3 CH ), 2.83 (q, J = 7.6 Hz, 2 H, CH ), 4.27 (m, 2 H,
2
2
13C NMR (CD
Hz, CHCF ), 55.3 (CH
CF ), 123.8, 129.9, 131.1, 135.5, 138.3, 141.9, 143.6, 145.5, 147.1,
CN): = 24.1, 25.4, 27.4 (CH ), 44.9 (q, J = 29.6
2
CH N), 4.45 (m, 1 H, CHCF ), 8.05 (s, 2 H, Cl C H ).
3
2
3
3
6
2
1
3
3
2
Cl ), 51.1 (CH N), 125.6 (q, J = 277.7 Hz,
2
2
C NMR (CD CN): = 10.9 (CH ), 21.2, 24.5, 25.8, 27.2 (CH ),
3
3
2
3
4
4.8 (q, J = 29.6 Hz, CHCF ), 50.5 (CH N), 125.7 (q, J = 277.7 Hz,
3 2
1
48.9 (Ar), 161.0, 165.2 (C=N).
Anal. Calcd for C20 Sb CH
.84. Found: C, 29.50; H, 1.99; N, 4.91.
CF ), 123.6, 131.9, 137.0, 137.1, 142.9 (Cl C H ), 160.4, 165.3
3
3
6
2
(C=N).
H14Cl
6
F
8
N
3
Cl : C, 29.07; H, 1.86; N,
2 2
4
Anal. Calcd for C H Cl F N Sb: C, 25.69; H, 2.16; N, 5.62.
1
6
16
9
3
3
Found: C, 25.42; H, 2.10; N, 5.56.
6h: Yield, 94%; white crystals (MeOH MeCN, 1:1); mp 220 °C.
IR (KBr): 2956, 1597, 1536, 1268, 1187 cm 1.
6
c: Yield: 89%; white crystals (MeOH MeCN, 1:1); mp 150 °C.
IR (KBr): 2946, 1556, 1273, 1182 cm 1.
1H NMR (CD
CH CN), 4.30 4.35 (m, 2 H, CH
.55 7.74 (m, 5 H, C H ), 8.02 8.64 (m, 4 H, 4-NO C H ).
CN): = 1.91 2.49, (m, 6 H, 3 CH
N), 4.49 4.54 (m, 1 H, CHCF
3
), 2.07 (s, 3 H,
3
2
1
3
2
),
H NMR (CD CN): = 1.76 2.50 (m, 6 H, 3 CH ), 4.21 4.48 (m,
3
2
7
6
5
2
6
4
5
H, CH N, CHCF , CH Ph), 7.22 7.43 (m, 5 H, C H ), 8.05 (s, 2
2 3 2 6 5
13C NMR (CD
CN): = 24.4, 25.2, 27.1 (CH
N), 125.6 (q, J = 277.7 Hz, CF
27.6, 130.0, 130.1, 130.8, 131.9, 132.1, 134.4, 135.0, 135.3, 136.1
Ar), 158.6, 159.9 (C=N).
), 44.3 (q, J = 29.6
H, Cl C H ).
3
2
3
6
2
1
3
Hz, CHCF
3
), 50.6 (CH
2
3
), 124.2,
C NMR (CD CN): = 24.4, 25.7, 27.2 (CH ), 33.7 (CH Ph), 44.8
3
2
2
1
(
(
q, J = 29.6 Hz, CHCF ), 50.5 (CH N), 125.6 (q, J = 277.7 Hz,
3 2
Synthesis 2002, No. 3, 349–354 ISSN 0039-7881 © Thieme Stuttgart · New York