Vol. 27, No. 4 (2015)
Synthesis of Piperazine Derivatives 1301
-
1
ν
1
8
max, cm ): 3444, 3042, 2940, 2814, 1649, 1599, 1481, 1229,
011; Anal. Calcd. for C18 Cl: C, 65.36; H, 5.79; N,
.47. Found: C, 65.30; H, 5.78; N, 8.43. MS (ESI) m/z: 330.84
General procedure for the synthesis of compounds (6a-
6i): To a solution of (E) hex-2-enoic acid 5 (0.01 mol) and
H
19
N O
2 2
different N-substituted benzyl piperazine (0.01 mol) in CH
2
Cl
2
+
[
M] .
(20 mL) was added ethyldiisopropylamine (0.02 mol), 1-(3-
dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride
(0.04 mol). The mixture was stirred at room temperature over-
night. The reaction mixture was partitioned between water and
(
E)-1-[4-(2-Methylbenzyl)piperazin-1-yl]-3-(furan-2-
yl)prop-2-en-1-one (4d): Yield: 96.7 ꢀ; m.p.: 243-245 °C;
H NMR (CDCl , 600 MHz) δ: 6.57 (d, 1H, furan-H), 6.44 (d,
H, =CH), 6.81 (d, 1H, =CH), 7.55 (s, 2H, furan-H), 7.52-
.63 (m, 2H, Ar-H), 7.34-7.47 (m, 2H, Ar-H), 3.62 (s, 2H,
1
3
1
7
CH
CH
CH
hydrochloric acid, aqueous NaHCO
over anhydrous MgSO . The solvent was evaporated to give
2
2
Cl . The organic layer was washed with 10 ꢀ aqueous
3
and brine and then dried
2
), 3.82 (s, 4H, pip), 2.69-2.75 (s, 4H, pip), 2.39 (s, 3H,
4
-1
3
); IR (KBr, νmax, cm ): 3426, 2924, 2522, 2432, 1645,
: C, 73.52;
the crude product. The obtained residue was purified by
recrystallized ethanol.
1
605, 1423, 1229, 1007;Anal. Calcd. for C19
H
22
N O
2 2
H, 7.14; N, 9.03. Found: C, 73.46; H, 7.06; N, 8.97. MS (ESI)
m/z: 310.39 [M] .
(E)-1-[4-(2-Chlorobenzyl)piperazin-1-yl]hex-2-en-1-
+
1
one (6a): Yield: 96.4 ꢀ; m.p.: 93-95 °C; H NMR (CDCl
3
,
(
E)-1-[4-(3-Methylbenzyl)piperazin-1-yl]-3-(furan-2-
600 MHz) δ: 7.22-7.41 (m, 4H,Ar-H), 6.81-6.83 (d, 1H, =CH),
1
yl)prop-2-en-1-one (4e): Yield: 95.8 ꢀ; m.p.: 221-224 °C; H
NMR (CDCl , 600 MHz) δ: 6.57 (d, 1H, furan-H), 6.45 (d, 1H,
CH), 6.81 (d, 1H, =CH), 7.57 (s, 2H, furan-H), 7.54-7.67 (m,
H, Ar-H), 7.38-7.45 (m, 2H, Ar-H), 3.62 (s, 2H, CH ), 4.08 (s,
H, pip), 2.72-2.92 (s, 4H, pip), 2.37 (s, 3H, CH ); IR (KBr,
max, cm ): 3412, 2974, 2522, 2404, 1715, 1477, 1371, 1271,
111; Anal. Calcd. for C19 : C, 73.52; H, 7.14; N, 9.03.
Found: C, 73.62; H, 7.18; N, 9.16. MS (ESI) m/z: 310.39 [M] .
E)-1-[4-(4-Methylbenzyl)piperazin-1-yl]-3-(furan-2-
6.17-6.21 (d, 1H, =CH), 3.61 (s, 2H, CH
2
), 3.56 (s, 2H, CH
2
),
),
3
3.38 (s, 4H, pip), 2.46 (s, 4H, pip), 1.32-2.24 (d, 2H, CH
2
-1
=
0.92-1.16 (m, 3H, CH
3
); IR (KBr, νmax, cm ): 2897, 2736, 1752,
OCl: C, 66.55;
2
4
ν
2
1615, 1394, 1068, 974;Anal. Calcd. for C17
H
23
N
2
3
H, 7.56; N, 9.13. Found: C, 66.62; H, 7.51; N, 9.24. MS
-1
+
(ESI) m/z: 306.83 [M] .
1
H
22
N O
2 2
(E)-1-[4-(3-Chlorobenzyl)piperazin-1-yl]hex-2-en-1-
+
1
one (6b): Yield: 95.3 ꢀ; m.p.: 97-98 °C; H NMR (CDCl
3
,
(
600 MHz) δ: 7.13-7.35 (m, 4H,Ar-H), 6.82-6.91 (d, 1H, =CH),
1
yl)prop-2-en-1-one (4f): Yield: 97.4 ꢀ; m.p.: 261-263 °C; H
NMR (CDCl , 600 MHz) δ: 6.58 (d, 1H, furan-H), 6.44 (d,
H, =CH), 6.81 (d, 1H, =CH), 7.57 (s, 2H, furan-H), 7.51-7.64
m, 2H, Ar-H), 7.35-7.46 (m, 2H, Ar-H), 3.62 (s, 2H, CH ),
); IR (KBr,
max, cm ): 3428, 2924, 2522, 2446, 1649, 1607, 1423, 1229,
011;Anal. Calcd. for C19 : C, 73.52; H, 7.14; N, 9.03.
6.17-6.24 (d, 1H, =CH), 3.63 (s, 2H, CH
3.42 (s, 4H, pip), 2.43 (s, 4H, pip), 1.42-2.29 (d, 2H, CH
2
), 3.51 (s, 2H, CH
2
),
),
3
2
-
1
1
(
4
ν
1
1.03-1.21 (m, 3H, CH
1614, 1421, 1057, 936; Anal. Calcd. for C17
3
); IR (KBr, νmax, cm ): 2907, 2851, 1748,
OCl: C,
2
H
23
N
2
.14 (s, 4H, pip), 2.72 (s, 4H, pip), 2.35 (s, 3H, CH
3
66.55; H, 7.56; N, 9.13. Found: C, 66.57; H, 7.61; N, 9.19.
-1
+
MS (ESI) m/z: 306.83 [M] .
H
22
N O
2 2
(E)-1-[4-(4-Chlorobenzyl)piperazin-1-yl]hex-2-en-1-
+
1
Found: C, 73.59; H, 7.21; N, 9.11. MS (ESI) m/z: 310.39 [M] .
E)-1-[4-(2-Fluorobenzyl)piperazin-1-yl]-3-(furan-2-
yl)prop-2-en-1-one (4g): Yield: 96.3 ꢀ; m.p.: 134-137 °C;
one (6c): Yield: 94.6 ꢀ; m.p.: 86-87 °C; H NMR (CDCl
3
,
(
600 MHz) δ: 7.22-7.30 (m, 4H,Ar-H), 6.80-6.89 (d, 1H, =CH),
6.16-6.21 (d, 1H, =CH), 3.66 (s, 2H, CH
3.45 (s, 4H, pip), 2.40 (s, 4H, pip), 1.42-2.19 (d, 2H, CH
2
), 3.52 (s, 2H, CH
2
),
),
1
H NMR (CDCl , 600 MHz) δ: 6.58 (d, 1H, furan-H), 6.44 (d,
H, =CH), 6.80 (d, 1H, =CH), 7.55 (s, 2H, furan-H), 7.51-
.64 (m, 2H, Ar-H), 7.25-7.46 (m, 2H, Ar-H), 3.42 (s, 2H,
3
2
-
1
1
7
0.88-0.93 (m, 3H, CH
1684, 1433, 1152, 956; Anal. Calcd. for C17
3
); IR (KBr, νmax, cm ): 2915, 2795, 1763,
OCl: C,
H
23
N
2
CH
2
), 3.82-4.14 (d, 4H, pip), 2.46 (d, 4H, pip); IR (KBr, νmax
,
66.55; H, 7.56; N, 9.13. Found: C, 66.51; H, 7.49; N, 9.22.
MS (ESI) m/z: 306.83 [M] .
-1
+
cm ): 3436, 3024, 2937, 2801, 1649, 1601, 1423, 1229, 1011;
Anal. Calcd. for C18 F: C, 68.77; H, 6.09; N, 8.91.
Found: C, 68.82; H, 6.15; N, 9.02. MS (ESI) m/z: 314.35 [M] .
E)-1-[4-(3-Fluorobenzyl)piperazin-1-yl]-3-(furan-2-
yl)prop-2-en-1-one (4h): Yield: 97.1 ꢀ; m.p.: 163-165 °C;
H
19
2
N O
2
(E)-1-[4-(2-Methylbenzyl)piperazin-1-yl]hex-2-en-1-
+
1
one (6d): Yield: 92.4 ꢀ; m.p.: 85-87 °C; H NMR (CDCl
3
,
(
600 MHz) δ: 7.19-7.26 (m, 4H,Ar-H), 6.80-6.90 (d, 1H, =CH),
6.19-6.23 (d, 1H, =CH), 3.68 (s, 2H, CH ), 3.53 (s, 2H, CH ),
3.49 (s, 4H, pip), 2.42 (s, 4H, pip), 2.41 (s, 3H, Ph-CH ), 1.43-
2.19 (d, 2H, CH ), 0.89-0.94 (m, 3H, CH ); IR (KBr, νmax, cm
): 2879, 2716, 1746, 1631, 1408, 1034, 949; Anal. Calcd. for
O: C, 75.48; H, 9.15; N, 9.78. Found: C, 75.51; H,
2
2
1
H NMR (CDCl
3
, 600 MHz) δ: 6.57 (d, 1H, furan-H), 6.44 (d,
3
-
1
7
H, =CH), 6.81 (d, 1H, =CH), 7.57 (s, 2H, furan-H), 7.43-
.57 (m, 2H, Ar-H), 7.23-7.34 (m, 2H, Ar-H), 3.43 (s, 2H,
2
3
1
CH
2
), 3.81-4.12 (d, 4H, pip), 2.83 (d, 4H, pip); IR (KBr, νmax
,
C
18
H
26
N
2
-
1
+
cm ): 3436, 3115, 2932, 2827, 1649, 1601, 1423, 1229, 1011;
Anal. Calcd. for C18 F: C, 68.77; H, 6.09; N, 8.91.
Found: C, 68.86; H, 6.24; N, 8.99. MS (ESI) m/z: 314.35 [M] .
E)-1-[4-(4-Fluorobenzyl)piperazin-1-yl]-3-(furan-2-
9.19; N, 9.83. MS (ESI) m/z: 286.41 [M] .
H
19
2
N O
2
(E)-1-[4-(3-Methylbenzyl)piperazin-1-yl]hex-2-en-1-
+
1
one (6e): Yield: 93.1 ꢀ; m.p.: 79-81 °C; H NMR (CDCl
3
,
(
600 MHz) δ: 7.16-7.28 (m, 4H,Ar-H), 6.80-6.91 (d, 1H, =CH),
6.19-6.24 (d, 1H, =CH), 3.67 (s, 2H, CH ), 3.56 (s, 2H, CH ),
3.49 (s, 4H, pip), 2.42 (s, 4H, pip), 2.59 (s, 3H, Ph-CH ), 1.45-
2.21 (d, 2H, CH ), 0.81-0.93 (m, 3H, CH ); IR (KBr, νmax, cm ):
2913, 2707, 1774, 1682, 1396, 1146, 953; Anal. Calcd. for
O: C, 75.48; H, 9.15; N, 9.78. Found: C, 75.56; H,
1
yl)prop-2-en-1-one (4i): Yield: 98 ꢀ; m.p.: 96-98 °C; H NMR
CDCl , 600 MHz) δ: 6.58 (d, 1H, furan-H), 6.44 (d, 1H, =CH),
.81 (d, 1H, =CH), 7.59 (s, 2H, furan-H), 7.22-7.48 (m, 2H,
Ar-H), 7.01-7.15 (m, 2H, Ar-H), 3.47 (s, 2H, CH ), 3.62-3.71
2
2
(
6
3
3
-1
2
3
2
-1
(
3
d, 4H, pip), 2.43 (d, 4H, pip); IR (KBr, νmax, cm ): 3436,
C
18
H
26
N
2
+
126, 2932, 2814, 1649, 1599, 1423, 1229, 1011;Anal. Calcd.
9.23; N, 9.84. MS (ESI) m/z: 286.41 [M] .
for C18
H
19
N
2
O
2
F: C, 68.77; H, 6.09; N, 8.91. Found: C, 68.59;
(E)-1-[4-(4-Methylbenzyl)piperazin-1-yl]hex-2-en-1-
+
1
H, 6.10; N, 8.87. MS (ESI) m/z: 314.35 [M] .
one (6f): Yield: 93.8 ꢀ; m.p.: 90-91 °C; H NMR (CDCl
3
,