2686 J. Agric. Food Chem., Vol. 58, No. 5, 2010
Table 1. Title Compounds 1a-1q
Liu et al.
Data for 5e: yield, 89.0%; mp, 177-178 °C; 1H NMR (CDCl3) δ 3.84
(s, 3H), 5.02 (s, 2H), 6.51 (s, 1H), 6.93 (d, J = 8.7 Hz, 2H), 7.69 (d, J =
8.7 Hz, 2H), 7.74-7.78 (m, 2H), 7.88-7.92 (m, 2H).
Data for 5f: yield, 97.0%; mp, 205-206 °C; 1H NMR (CDCl3) δ 1.33
(s, 9H), 5.03 (s, 2H), 6.54 (s, 1H), 7.44 (d, J = 8.4 Hz, 2H), 7.69 (d, J =
8.4 Hz, 2H), 7.74-7.78 (m, 2H), 7.88-7.92 (m, 2H).
Data for 5g: yield, 85.2%; mp, 152-154 °C; 1H NMR (CDCl3) δ 5.06
(s, 2H), 6.73 (s, 1H), 7.31 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.48 (d, J = 2.0 Hz,
1H), 7.64 (d, J = 8.4 Hz, 1H), 7.75-7.78 (m, 2H), 7.80-7.91 (m, 2H).
Data for 5h: yield, 86.0%; mp, 109-110 °C; 1H NMR (CDCl3) δ 1.24
(d, J = 6.9 Hz, 6H), 2.97-3.06 (m, 1H), 4.95 (s, 2H), 6.11 (s, 1H),
7.74-7.77 (m, 2H), 7.78-7.91 (m, 2H).
compd
R1
phenyl
R2
compd
R1
R2
1a
1b
1c
1d
1e
1f
MeS
i-Pr
1j
4-t-Bu-phenyl
4-t-Bu-phenyl
MeS
i-Pr
phenyl
2-Cl-phenyl
1k
1l
i-Pr
2,4-Cl2-phenyl
2,4-Cl2-phenyl
MeS
i-Pr
Data for 5i: yield, 70.0%; mp, 156-157 °C; 1H NMR (CDCl3) δ 4.99 (s,
2H), 6.36 (s, 1H), 7.73-7.79 (m, 2H), 7.79-7.92 (m, 2H).
4-Cl-phenyl
4-Cl-phenyl
MeS
i-Pr
1m
1n
1o
1p
1q
i-Pr
i-Pr
Br
MeS
i-Pr
General Synthetic Procedures for 6a-6i. To a suspension of
N-substituted phthalimide 5 (4 mmol) in ethanol (20 mL) was added
hydrazine hydrate (50%, 0.48 g, 4.8 mmol). The reaction mixture was
refluxed for 5 h and then cooled. The precipitated phthalylhydrazide was
filtered off and washed with ethanol, and then the filtrate was concentrated
under reduced pressure to give crude 6, which was utilized in the next
reaction without further purification.
2-OCH3-phenyl
2-OCH3-phenyl
4-OCH3-phenyl
4-OCH3-phenyl
MeS
i-Pr
1g
1h
1i
MeS
i-Pr
MeS
i-Pr
Br
Data for 4a: yield, 73.1%; mp, 87-89 °C (88 °C (14)); 1H NMR
(CDCl3) δ 4.51 (s, 2H), 6.63 (s, 1H), 7.42-7.47 (m, 3H), 7.78-7.81
(m, 2H).
Data for 4b: yield, 84.3%; oil; 1H NMR (CDCl3) δ 4.53 (s, 2H), 6.80
(s, 1H), 7.32-7.40 (m, 2H), 7.46-7.50 (m, 1H), 7.74 (dd, J = 7.2 Hz,
2.1 Hz, 1H).
1
Data for 6a: yield, 94.3%; mp, 61-62 °C (51-52 °C (17)); H NMR
(CDCl3) δ 1.64 (s, 2H), 4.01 (s, 2H), 6.45 (s, 1H), 7.43-7.46 (m, 3H),
7.77-7.80 (m, 2H).
Data for 6b: yield, 98.5%; oil; 1H NMR (CDCl3) δ 1.75 (s, 2H), 4.04
(s, 2H), 6.60 (s, 1H), 7.34-7.38 (m, 2H), 7.46-7.50 (m, 1H), 7.70-7.78
(m, 1H).
Data for 4c: yield, 60.7%; mp, 117-119 °C (118-120 °C (15));
1H NMR (CDCl3) δ 4.51 (s, 2H), 6.61 (s, 1H), 7.44 (d, J = 8.4 Hz,
2H), 7.73 (d, J = 8.4 Hz, 2H).
Data for 6c: yield, 82.7%; mp, 79-81 °C (81 °C (18)); 1H NMR
(CDCl3) δ 1.58 (s, 2H), 4.02 (s, 2H), 6.43 (s, 1H), 7.42 (d, J = 8.4 Hz, 2H),
7.72 (d, J = 8.4 Hz, 2H).
Data for 4d: yield, 95.1%; 1H NMR(CDCl3) δ 3.90 (s, 3H), 4.52 (s, 2H),
6.84 (s, 1H), 6.98-7.08 (m, 2H), 7.43 (td, J = 7.8 Hz, 1.8 Hz, 1H), 7.89
(dd, J = 7.8 Hz, 1.8 Hz, 1H).
Data for 6d: yield, 95.0%; oil; 1H NMR (CDCl3) δ 1.87 (s, 2H), 3.85
(s, 3H), 3.98 (s, 2H), 6.61 (s, 1H), 6.94-7.02 (m, 2H), 7.37 (t, J = 7.6 Hz,
1H), 7.82 (d, J = 7.6 Hz, 1H).
Data for 4e: yield, 60.0%; mp, 86-87 °C; 1H NMR (CDCl3) δ 3.86
(s, 3H), 4.50 (s, 2H), 5.58 (s, 1H), 6.97 (d, J = 8.7 Hz, 2H), 7.73 (d, J =
8.7 Hz, 2H).
Data for 6e: yield, 92.0%; mp, 111-112 °C;1H NMR (CDCl3) δ 1.58
(s, 2H), 3.85 (s, 3H), 4.01 (s, 2H), 6.40 (s, 1H), 6.97 (d, J = 8.8 Hz, 2H),
7.73 (d, J = 8.8 Hz, 2H).
Data for 4f: yield, 62.0%; mp, 75-76 °C; 1H NMR (CDCl3) δ 1.35
(s, 9H), 4.50 (s, 2H), 6.61 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H), 7.72 (d, J =
8.4 Hz, 2H).
Data for 6f: yield, 95.7%; mp, 65-67 °C; 1H NMR (CDCl3) δ 1.35
(s, 9H), 1.62 (s, 2H), 4.02 (s, 2H), 6.43 (s, 1H), 7.47 (d, J = 8.4 Hz, 2H),
7.73 (d, J = 8.4 Hz, 2H).
1
Data for 4g: yield, 90.1%; mp, 57-59 °C (61-62 °C (12)); H NMR
Data for 6g: yield, 97.2%;1H NMR (CDCl3) δ 1.59 (s, 2H), 4.05 (s, 2H),
6.60 (s, 1H), 7.33 (dd, J = 8.4 Hz, 2.0 Hz, 1H), 7.50 (d, J = 2.0 Hz, 1H),
7.67 (d, J = 8.4 Hz, 1H).
(CDCl3) δ 4.53 (s, 2H), 6.68 (s, 1H), 7.35 (dd, J = 8.4 Hz, 2.1 Hz, 1H), 7.52
(d, J = 2.1 Hz, 1H), 7.71 (d, J = 8.4 Hz, 1H).
Data for 4h: yield, 78.4%; oil; 1H NMR (CDCl3) δ 1.28 (d, J = 6.9 Hz,
6H), 3.01-3.09 (m, 1H), 4.44 (s, 2H), 6.20 (s, 1H).
Data for 6h: yield, 97.0%; oil;1H NMR (CDCl3) δ 1.27 (d, J = 6.9 Hz,
6H), 1.60 (s, 2H), 3.01-3.08 (m, 1H), 3.93 (s, 2H), 6.01 (s, 1H).
Data for 6i: yield, 95.6%; oil;1H NMR (CDCl3) δ 1.57 (s, 2H), 3.94 (s,
2H), 6.21 (s, 1H).
Synthetic Procedure for 4i (16). A solution of dibromoformaloxime
(4.1 g, 20 mmol) in dichloromathane (20 mL) was added over 5 h to a
stirred solution of propargyl bromide (2.86 g, 24 mmol), potassium
bicarbonate (2.5 g, 30 mmol), dichloromethane (100 mL), and water
(10 mL). After 2 h, water (50 mL) was added. The organic layer was
separated and dried over anhydrous magnesium sulfate, filtered, and
concentrated in vacuo. The residue was purified by flash chromatography
on a silica gel to afford compound 4i as a colorless oil, yield 50.0%: 1H
NMR (CDCl3) δ 4.44 (s, 2H), 6.41 (s, 1H).
General Synthetic Procedures for the Title Compounds 1a-1q.
A mixture of 7a (or 7b) (1.35 mmol) and crude 6 (1.45 mmol) in ethanol
(20 mL) was refluxed for 2 h and then evaporated under reduced pressure
to give crude product. The residue was purified by flash chromatography
on a silica gel to afford the title compounds.
Data for 1a: yield, 98.3%; mp, 86-88 °C;1H NMR (CDCl3) δ 1.21
(t, 3JHH = 7.2 Hz, 3H, CH3), 2.72 (s, 3H, SCH3), 3.58 (q, 3JHH = 7.2 Hz,
2H, OCH2), 3.71 (t, 3JHH = 5.1 Hz, 2H, CH2O), 4.33 (t, 3JHH = 5.1 Hz,
2H, CO2CH2), 4.97 (d, 3JHH = 6.0 Hz, 2H, CH2N), 6.51 (s, 1H, isoxazole),
7.46-7.48 (m, 3H, Ph), 7.78-7.80 (m, 2H, Ph), 10.41 (s, 1H, NH). Anal.
Calcd for C19H21N3O4S: C, 58.90; H, 5.46; N, 10.85. Found: C, 58.88; H,
5.30; N, 10.68.
General Synthetic Procedures for 5a-5i. To a solution of 4
(6 mmol) in N,N-dimethylformamide (10 mL) was added potassium
phthalimide (6 mmol) in portions. After the mixture was stirred at room
temperature for 5 h, water (50 mL) was added, and the precipitate was
collected by filtration and washed with water. After recrystallization from
ethanol, N-substituted phthalimide 5 was obtained as a white crystal.
Data for 5a: yield, 98.5%; mp, 162-164 °C; 1H NMR (CDCl3) δ 5.04
(s, 2H), 6.57 (s, 1H), 7.41-7.43 (m, 3H), 7.74-7.77 (m, 4H), 7.88-7.92
(m, 2H).
Data for 1b: yield, 90.5%; mp, 88-89 °C;1H NMR (CDCl3) δ 1.22
(t, JHH = 7.2 Hz, 3H, CH3), 1.44 (d, JHH = 7.2 Hz, 6H, C(CH3)2),
3
3
3
3.19-3.22 (m, 1H, CH), 3.58 (q, JHH = 7.2 Hz, 2H, OCH2), 3.71 (t,
3JHH = 5.1 Hz, 2H, CH2O), 4.31 (t, 3JHH = 5.1 Hz, 2H, CO2CH2), 4.77 (d,
3JHH = 6.0 Hz, 2H, CH2N), 6.53 (s, 1H, isoxazole), 7.47-7.48 (m, 3H,
Ph), 7.78-7.80 (m, 2H, Ph), 10.68 (s, 1H, NH). Anal. Calcd for
C21H25N3O4: C, 65.51; H, 6.37; N, 11.09. Found: C, 65.78; H, 6.57;
N, 10.96.
Data for 5b: yield, 84.0%; mp, 120-121 °C; 1H NMR (CDCl3) δ 5.06
(s, 2H), 6.74 (s, 1H), 7.26-7.48 (m, 3H), 7.68 (d, J = 7.2 Hz, 1H),
7.74-7.78 (m, 2H), 7.88-7.92 (m, 2H).
Data for 5c: yield, 96.3%; mp, 173-175 °C; 1H NMR (CDCl3) δ 5.03 (s,
2H), 6.54 (s, 1H), 7.39 (d, J = 8.4 Hz, 2H), 7.68 (d, J = 8.4 Hz, 2H),
7.74-7.78 (m, 2H), 7.88-7.91 (m, 2H).
Data for 1c: yield, 87.3%; mp, 64-65 °C;1H NMR (CDCl3) δ 1.21
(t, JHH = 7.2 Hz, 3H, CH3), 1.45 (d, JHH = 7.2 Hz, 6H, C(CH3)2),
3
3
Data for 5d: yield, 98.2%;mp, 149-151 °C;1H NMR (CDCl3) δ 3.87 (s,
3H), 5.03 (s, 2H), 6.78 (s, 1H), 6.95-7.02 (m, 2H), 7.38 (t, J = 6.8 Hz, 1H),
7.72-7.76 (m, 2H), 7.81 (dd, J = 6.8 Hz, 4.6 Hz, 1H), 7.87-7.90 (m, 2H).
3
3.19-3.22 (m, 1H, CH), 3.58 (q, JHH = 7.2 Hz, 2H, OCH2), 3.70 (t,
3JHH = 4.8 Hz, 2H, CH2O), 4.30 (t, 3JHH = 4.8 Hz, 2H, CO2CH2), 4.78 (d,
3JHH = 6.4 Hz, 2H, CH2N), 6.69 (s, 1H, isoxazole), 7.35-7.44 (m, 2H,