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Wang et al.
Synthesis of Compounds 6a-c. General Procedure
To a stirred mixture of 5a-c (0.01 mol) and paraformaldehyde (0.45 g, 0.015 mol) was added
3 ml of conc. hydrochloric acid (37%) at room temperature. Then, the mixture was stirred at
40◦C for 1 h, Water (10 ml) was then added and the mixture was extracted with petroleum
ether (4 × 10 ml), and the combined organic extracts were washed with brine. The solution
was dried over Na2SO4 and concentrated in vacuo to afford desired compounds which were
used in the next step without further purification.
Compound 6a,7 yellow oil, 90% yield.
1H NMR (500 MHz,CDCl3): δ 4.69 (s,2H), 3.89 (s,3H),3.86 (s,3H), 3.84 (s,3H), 2.26
(s,3H).
Compound 6b,10 yellow oil, 96% yield
1H NMR (300 MHz, CDCl3): δ 4.70 (s,2H), 3.90 (s, 3H), 3.88(s, 3H), 3.87 (s, 3H),
2.46 (s, 3H).
Compound 6c,7 yellow oil, 97% yield.
1H NMR (500 MHz, CDCl3): δ 4.68(s, 2H), 3.92 (s, 3H), 3.91 (s, 3H), 3.89 (s, 3H),
3.78 (s, 3H), 2.28 (s, 3H).
Synthesis of Compounds 7a-c. General Procedure
A suspension of 6a-c (10 mmol), N-benzylpiperazine (1.76 g, 10 mmol) and K2CO3 (1.65 g,
12 mmol) in CH2Cl2 (10 ml) were heated at 40◦C for 2 h; the progress of the reaction was
monitored by TLC. Water was added and the mixture was extracted with CH2Cl2 (30 ml)
washed with brine, dried over Na2SO4 and concentrated in vacuo. Then the concentrated oil
was dissolved in methanol and conc. HCl was added dropwise until the pH of the solution
at 1∼2. The white precipitate that formed immediately was collected and recrystallized
from methanol to afford the hydrochloride salts 7a-c.
Compound 7a, white solid, mp. 226-228◦C, 89% yield.
1H NMR (300 MHz, MeOD): δ 7.65 (s, 2H), 7.54-7.53 (m, 3H), 6.76 (s, 1H), 4.52
(s,2H), 4.46 (s, 2H), 4.01 (s, 3H), 3.86 (s, 3H), 3.83 (s, 3H), 3.75 (br, s, 8H), 2.47 (s, 3H).
13C NMR (75 MHz, MeOD): δ 156.9, 154.2, 140.9, 136.8, 132.7 (2C), 131.6, 130.5
(2C), 129.3, 113.3, 111.1, 61.9, 61.3, 56.5, 20.2. TOF-MS: m/z 371 (M++H). Calcd for
C22H31O3N2: 371.2334. Found: 371.2329.
Anal. Calcd for C22H32Cl2N2O3: C, 59.59; H. 7.27; N. 6.32. Found: C, 59.64; H, 7.29;
N, 6.34.
Compound 7b, white solid, mp. 221-222◦C, 88% yield.
1H NMR (300 MHz, MeOD): δ 7.69-7.65(m,2H), 7.52-7.51(s,2H), 4.60(s,2H), 4.55
(s,2H), 4.03 (s,3H), 3.92(s,3H), 3.91(s,3H), 3.80(br,s,4H), 3.75(br,s,4H),2.57(s,3H).
13CNMR(75 MHz, MeOD): 154.9, 154.3, 145.9, 136.5, 132.7(2C), 131.6, 130.5(2C),
129.4, 118.2, 116.9, 62.1, 61.7, 61.3, 54.7,21.2. TOF-MS: m/z 449 (M++H). Calcd for
C22H31BrN2O3:449.1440. Found: 449.1443.
Anal. Calcd for C22H31BrCl2N2O3: C, 50.59; H, 5.98; N, 5.36. Found: C, 50.63; H,
6.00; N, 5.35.
Compound 7c, white solid, mp. 202–204◦C, yield 92%.
1H NMR (300 MHz,CDCl3):
δ
7.66-7.64(m,2H),7.53-7.51(m,3H),4.53(s,2H),
4.50(s,2H), 3.96(s,3H), 3.91(s,3H), 3.80(s,3H),3.79(br,s,4H),3.72(br,s,4H),2.36(s,3H).