(t, J = 5.9, 2H), 7.08 (d, J = 2.4, 1H), 7.15 (dd, J = 2.4, 9.0, 1H),
7.20–7.34 (m, 5H), 7.47 (dd, J = 1.9, 8.8, 1H), 7.56 (d, J = 8.8, 1H),
7.61 (d, J = 9.0, 1H), 7.89 (d, J = 1.9, 1H); 13C NMR (CDCl3) d
41.0, 53.0, 53.7, 57.1, 63.0, 106.7, 117.0, 120.0, 127.0, 128.2, 128.3,
128.4, 129.2, 129.56, 129.60, 130.0, 133.0, 138.1, 157.0.
7.29–7.47 (m, 7H); 13C NMR (D2O) d 25.4, 32.0, 48.9, 49.4, 56.2,
56.8, 61.7, 115.1, 122.6, 127.1, 129.0, 129.3, 130.4, 140.7, 157.5;
MS (ESI) m/z 325 ([M - HCl2]+), 319, 293, 282, 236; HRMS
(ESI) calcd for C21H29N2O [M - HCl2]+ 325.2280, found 325.2281.
1-(3-Phenylpropyl)-4-[2-(4-propylphenoxy)ethyl]piperazine dihy-
drochloride (3n). White crystalline powder (1700 mg, 77%); mp
193–197 ◦C; Anal. Calcd for C24H34N2O¥2HCl¥1/3H2O: C 64.71,
1-Benzyl-4-[2-(2,6-dimethylphenoxy)ethyl]piperazine dihydro-
chloride (3f). White crystalline powder (1100 mg, 55%); mp
◦
1
205–209 C; Anal. Calcd for C21H28N2O¥2HCl¥2 H2O: C 62.07,
H 8.30, N 6.29. Found: C 64.76, H 8.66, N 6.54%; IR (KBr)
H 7.69, N 6.89. Found: C 62.34, H 7.95, N 7.23%; IR (KBr)
1
n
max/cm-1 1609, 1510, 1450, 1374, 1237; H NMR (DMSO-d6) d
1
n
max/cm-1 1478, 1454, 1431, 1412, 1373, 1330, 1195; H NMR
0.87 (t, J = 7.3, 3H), 1.55 (m, 2H), 2.06 (m, 2H), 2.49 (m, 2H), 2.66
(t, J = 7.7, 2H), 3.44–3.91 (m, 12H), 4.42 (d, J = 4.5, 2H), 6.93
(AA¢XX¢, J = 8.4, 2H), 7.12 (AA¢XX¢, J = 8.4, 2H), 7.17– 7.35 (m,
5H), 12.34 (bs, 2H); 13C NMR (DMSO-d6) d 13.4, 24.2, 24.6, 31.8,
36.3, 47.8, 48.5, 54.5, 55.2, 62.2, 114.5, 126.0, 128.1, 128.3, 129.1,
134.9, 140.4, 155.4; MS (ESI) m/z 367 ([M - HCl2]); HRMS (ESI)
calcd for C24H35N2O [M - HCl2]+ 367.2749, found 367.2763.
(D2O) d 2.20 (s, 6H), 3.63–3.90 (m, 10H), 4.19 (t, J = 4.9, 2H),
4.47 (s, 2H), 6.97–7.07 (m, 3H), 7.51 (s, 5H); 13C NMR (D2O) d
16.1, 48.3, 49.6, 57.1, 61.0, 65.3, 125.5, 127.8, 129.6, 129.9, 131.2,
131.3, 131.7, 155.0; MS (ESI) m/z 325 ([M - HCl2]+), 196, 158,
141, 77; HRMS (ESI) calcd for C21H29N2O [M - HCl2]+ 325.2280,
found 325.2274.
1-Benzyl-4-[2-(phenylthio)ethyl]piperazine dihydrochloride (3g).
◦
White crystalline powder (1000 mg, 52%); mp 188–192 C, dec.;
1,5-bis{4-[2-(4-Bromophenoxy)ethyl]piperazin-1-yl}pentane tet-
rahydrochloride (3o). Off-white crystalline powder (975 mg,
62%); mp 235–242 ◦C, dec.; Anal. Calcd for C29H42Br2N4O2¥
4HCl¥H2O: C 43.41; H 6.03; N 6.98. Found: C 43.21, H 5.85,
N 7.00%; IR (KBr) nmax/cm-1 1490, 1459, 1447, 1413, 1373, 1235;
1H NMR (D2O) d 1.45 (m, 2H), 1.82 (m, 4H), 3.30 (t, J = 8.1,
4H), 3.55–3.90 (m, 20H), 4.38 (t, J = 4.8, 4H), 6.94 (AA¢XX¢, J =
9.0, 4H), 7.49 (AA¢XX¢, J = 9.0, 4H); 13C NMR (D2O) d 23.1,
23.3, 49.0, 49.4, 56.1, 56.9, 62.1, 114.1, 117.0, 132.9, 156.8; MS
(ESI) m/z 641, 639, 637 ([M - H3Cl4]+), 355, 353, 321, 320, 319;
HRMS (ESI) calcd for C29H43Br2N4O2 [M - H3Cl4]+ 637.1753,
found 637.1752.
Anal. Calcd for C19H24N2S¥2HCl: C 59.21, H 6.80, N 7.27. Found:
C 58.98, H 6.99, N 7.20%; IR (KBr) nmax/cm-1 1581, 1482, 1439,
1
1402, 1372; H NMR (D2O) d 3.36 (m, 2H), 3.47 (m, 2H), 3.67
(m, 8H), 4.50 (s, 2H), 7.35–7.63 (m, 10H); 13C NMR (D2O) d
27.8, 48.4, 49.2, 55.9, 60.9, 127.8, 128.4, 129.9, 130.1, 131.1, 131.3,
131.7, 132.8; MS (ESI) m/z 313 ([M - HCl2]+); HRMS (ESI) calcd
for C19H25N2S [M - HCl2]+ 313.1738, found 313.1747.
2-{[2-(4-Benzylpiperazin-1-yl)ethyl]thio}benzo[d]thiazole dihy-
drochloride (3h). White crystalline powder (365 mg, 17%); mp
191–195 ◦C; IR (KBr) nmax/cm-1 1457, 1428, 1403, 1372; 1H NMR
(D2O) d 3.52–3.73 (m, 12H), 4.42 (s, 2H), 7.33 (t, J = 7.6, 1H),
7.39–7.56 (m, 6H), 7.69 (d, J = 8.0, 1H), 7.79 (d, J = 8.0, 1H); 13
C
1-Benzyl-4-ethylpiperazine dihydrochloride (3j). A mixture of
1b (1.23 g, 5 mmol) and NaBH4 (0.39 g, 10 mmol) in diglyme
(10 mL) was stirred for 6 h under reflux. A sample of the reaction
NMR (D2O) d 48.5, 49.4, 56.1, 60.90, 60.94, 121.1, 122.2, 125.6,
127.2, 127.7, 129.9, 131.1, 131.7, 135.3, 152.2, 166.9; MS (ESI)
m/z 370 ([M - HCl2]+), 203, 196, 158, 141, 113; HRMS (ESI)
calcd for C20H24N3S2 [M - HCl2]+ 370.1406, found 370.1402.
1
mixture was analyzed with H NMR and HPLC to determine
the ratio of 3j and toluene (4j) formed. The reaction mixture was
diluted with water (80 mL), extracted with ethyl acetate (60 mL),
washed with water (3 ¥ 50 mL), the organic phase was back
extracted with 0.5 M HCl(aq) (25 mL) and this aqueous solution
evaporated in vacuo. The residue was recrystallized from ethanol
to give a white crystalline solid (525 mg, 41%): mp 247–250 ◦C
(lit.25 250 ◦C, dec.); IR (KBr) nmax/cm-1 1638 (br), 1474, 1457,
2-[2-(4-Benzylpiperazin-1-yl)ethyl]isoindoline-1,3-dione dihydro-
chloride (3i). Gray crystalline powder (920 mg, 44%); mp 196–
199 ◦C; IR (KBr) nmax/cm-1 1710, 1435, 1421, 1402, 1389; H
1
NMR (D2O) d 3.53–3.86 (m, 10H), 4.05 (t, J = 5.8, 2H), 4.42 (s,
2H), 7.45 (m, 5H), 7.75 (s, 4H); 13C NMR (D2O) d 32.6, 48.4, 49.3,
55.1, 60.9, 124.1, 127.7, 129.9, 131.1, 131.5, 131.7, 135.5, 170.3;
MS (ESI) m/z 350 ([M - HCl2]+), 196, 158, 141; HRMS (ESI)
calcd for C21H24N3O2 [M - HCl2]+ 350.1869, found 350.1866.
1
1449, 1441, 1420; H NMR (D2O) d 1.40 (t, J = 7.3, 3H), 3.40
(q, J = 7.3, 2H), 3.46–3.95 (m, 8H), 4.54 (s, 2H), 7.59 (m, 5H);
13C NMR (D2O) d 9.0, 48.5, 48.6, 52.8, 60.9, 127.9, 129.9, 131.1,
131.7.
1-Allyl-4-(2-phenoxyethyl)piperazine
dihydrochloride
(3l).
White crystalline powder (600 mg, 38%); mp 193–198 ◦C; IR
(KBr) nmax/cm-1 1599, 1495, 1444, 1416, 1401; 1H NMR (D2O) d
3.60–3.91 (m, 10H), 3.95 (d, J = 6.9, 2H), 4.46 (t, J = 4.8, 2H),
5.69 (m, 2H), 5.96 (m, 1H), 7.09 (m, 3H), 7.42 (m, 2H); 13C NMR
(D2O) d 48.2, 49.5, 56.2, 59.3, 61.7, 115.1, 122.6, 124.8, 128.6,
130.4, 157.5; MS (ESI) m/z 247 ([M - HCl2]+), 205, 164, 99;
HRMS (ESI) calcd for C15H23N2O [M - HCl2]+ 247.1810, found
247.1820.
1-Benzyl-4-(2-methoxyethyl)piperazine dihydrochloride (3k).
A mixture of 1b (1.23 g, 5 mmol) and NaOCH3 (0.55 g, 10 mmol)
in diglyme (10 mL) was stirred for 4 h at 140 ◦C. A sample of the
1
reaction mixture was analyzed with H NMR. The product was
isolated as described above to give a white crystalline solid (920
mg, 60%): mp 193–196 ◦C, dec.; IR (KBr) nmax/cm-1 1604, 1498,
1455, 1379; 1H NMR (D2O) d 3.41 (s, 3H), 3.54 (t, J = 5.0, 2H),
3.62–3.79 (m, 8H), 3.82 (t, J = 5.0, 2H), 4.52 (s, 2H), 7.56 (m, 5H);
13C NMR (D2O) d 48.3, 49.2, 56.3, 58.9, 60.9, 65.5, 127.9, 129.9,
131.1, 131.7; MS (ESI) m/z 235 ([M - HCl2]+), 214, 196, 158, 141;
HRMS (ESI) calcd for C14H23N2O [M - HCl2]+ 235.1810, found
235.1800.
1-(2-Phenoxyethyl)-4-(3-phenylpropyl)piperazine dihydrochlo-
ride (3m). White crystalline powder (1183 mg, 41%); mp
203–206 ◦C; IR (KBr) nmax/cm-1 1597, 1497, 1452, 1292, 1246;
1H NMR (D2O) d 2.12 (m, 2H), 2.77 (t, J = 7.4, 2H), 3.31 (m,
2H), 3.62–3.92 (m, 10H), 4.44 (t, J = 4.8, 2H), 7.04–7.16 (m, 3H),
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The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 1300–1310 | 1307
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