1542
C.-F. Lin et al. / Bioorg. Med. Chem. 13 (2005) 1537–1544
broad. MS spectra were measured with an HP 5995 GC–
MS instrument. The UV spectra were recorded on a Shi-
madzu UV-160A UV–vis recording spectrophotometer
as methanolic solutions. Elemental analyses (C, H, N)
were performed on a Perkin–Elmer 2400 Series II
CHNS/O analyzer and the results were within ±0.4%
of the calculated values.
4.1.5. 1-[3-(Benzyloxy)phenyl]ethanone (21). Yield, 75%;
MS (EI, 70 eV): m/z 226 (M ); Found: C, 79.57; H,
+
6.14. C H O requires: C, 79.65; H, 6.19; UV k
1
5
14
2
max
(loge): 216.0 (4.60), 249.0 (4.12), 305.0 (3.62); IR
ꢀ
1 1
(KBr): 1685 (C@O) cm ; H NMR (200 MHz, CDCl ):
3
d 2.60 (s, 3H), 5.12 (s, 2H), 7.19 (ddd, 1H, J = 8.2, 2.4,
1.1 Hz), 7.30–7.49 (m, 6H), 7.54–7.60 (m, 2H);
1
3
C
NMR (50 MHz, CDCl ): d 26.53, 69.95, 113.32,
3
4
.1. Preparation of substituted benzyloxybenzenes (17–31)
120.07, 121.11, 127.36, 127.93, 128.44, 129.42, 136.27,
1
38.27, 158.74, 197.71.
Substituted phenols (1–12) (0.1 mol) was dissolved in
THF (100 mL). To the solution was added substituted
benzyl chlorides (13–16) (0.13 mol), K CO (20 g), and
KI (26 g). The resulting mixture was stirred under reflux
for 6 h. The solvent was removed in vacuo. Water
4.1.6. 1-[4-(Benzyloxy)phenyl]ethanone (22). Yield, 93%;
+
mp 89–90 ꢁC; MS (EI, 70 eV): m/z 226 (M ); Found:
2
3
C, 79.62; H, 6.10. C H O requires: C, 79.65; H,
6.19; UV kmax (loge): 211.0 (4.46), 269.0 (4.57); IR
1
5
14
3
ꢀ
1 1
(KBr): 1678 (C@O) cm ; H NMR (200 MHz, CDCl ):
(
CHCl , dried over MgSO , and evaporated. The residue
100 mL) was added and the mixture was extracted with
3
d 2.56 (s, 3H), 5.14(s, 2H), 7.02 (d, 2H, J = 8.9 Hz),
7.37–7.45 (m, 5H), 7.95 (d, 2H, J = 8.9 Hz); C NMR
3
4
13
was purified by column chromatography over silica gel,
eluting with n-hexane/EtOAc to yield the corresponding
substituted benzyloxybenzenes (17–31) (Table 1).
(50 MHz, CDCl ): d 26.12, 69.90, 114.32, 127.24,
3
128.02, 128.47, 130.38, 130.48, 135.95, 162.39, 196.54.
8
4
4
7
.1.1. 2-(Benzyloxy)benzaldehyde (17). Yield, 87%; mp
4.1.7. Methyl 2-(benzyloxy)benzoate (23). Yield, 87%;
MS (EI, 70 eV): m/z 242 (M ); Found: C, 74.18; H,
+
+
8–49 ꢁC; MS (EI, 70 eV): m/z 212 (M ); Found: C,
9.17; H, 5.54. C H O requires: C, 79.25; H, 5.66;
5.74. C H O requires: C, 74.30; H, 5.78; UV k
1
4
12
2
15 14
3
max
UV kmax (loge): 215.4 (4.46), 253.6 (4.00), 318.2 (3.89);
(loge): 211.0 (4.60), 294.0 (4.60); IR (KBr): 1728
ꢀ
1
1
ꢀ1
1
IR (KBr): 1685 (C@O) cm
;
H NMR (200 MHz,
(C@O) cm ; H NMR (200 MHz, CDCl ): d 3.92 (s,
3
CDCl ): d 5.20 (s, 2H), 7.01–7.09 (m, 2H), 7.35–7.48
3H), 5.19 (s, 2H), 6.97–7.04(m, 2H), 7.32–7.54(m,
6H), 7.85 (dd, 1H, J = 8.0, 2.0 Hz);
3
1
3
(
1
m, 5H), 7.54(ddd, 1H, J = 8.2, 7.6, 1.9 Hz), 7.87 (dd,
H, J = 8.0, 2.0 Hz), 10.58 (s, 1H);
C NMR
(50 MHz, CDCl ): d 51.79, 70.35, 113.67, 120.36,
1
3
C
NMR
3
(
1
1
50 MHz, CDCl ): d 70.24, 112.82, 120.80, 124.96,
27.08, 128.06, 128.23, 128.52, 135.70, 135.86, 160.84,
89.54.
120.55, 126.59, 127.55, 128.32, 131.55, 133.19, 136.56,
156.90, 166.78.
3
8
4
.1.8. 2-(Benzyloxy)benzamide (24). Yield, 95%; mp
8
+
4
5
7
.1.2. 3-(Benzyloxy)benzaldehyde (18). Yield, 92%; mp
114–115 ꢁC; MS (EI, 70 eV): m/z 227 (M ); Found: C,
+
7–58 ꢁC; MS (EI, 70 eV): m/z 212 (M ); Found: C,
74.08; H, 5.65; N, 6.14. C H NO requires: C, 74.00;
H, 5.73; N, 6.17; UV kmax (loge): 210.0 (4.57), 290.0
1
4
13
2
9.20; H, 5.59. C H O requires: C, 79.25; H, 5.66;
1
4
12
2
ꢀ
1 1
(4.43); IR (KBr): 1647 (C@O) cm ; 3406 (NH ); H
UV kmax (loge): 215.0 (4.57), 251.0 (4.46), 311.0 (3.92);
IR (KBr): 1685 (C@O) cm
CDCl ): d 5.13 (s, 2H), 7.23–7.32 (m, 1H), 7.34–7.49
(
0
1
2
ꢀ
1
1
;
H NMR (200 MHz,
NMR (200 MHz, CDCl ): d 5.19 (s, 2H), 6.08 (br,
3
1H), 7.05–7.14(m, 2H), 7.38–7.52 (m, 6H), 7.75 (br,
1H), 8.25 (dd, 1H, J = 7.8, 1.9 Hz);
3
1
3
13
C NMR
(50 MHz, CDCl ): d 71.06, 112.45, 120.92, 121.29,
m, 8H), 9.98 (s, 1H); C NMR (50 MHz, CDCl ): d
3
.01, 113.07, 121.97, 123.45, 127.32, 127.99, 128.46,
29.90, 136.09, 137.61, 159.10, 191.85.
3
127.64, 128.49, 128.75, 132.46, 133.12, 135.34, 156.90,
1
66.78.
8
4
6
7
.1.3. 4-(Benzyloxy)benzaldehyde (19). Yield, 92%; mp
+
7–68 ꢁC; MS (EI, 70 eV): m/z 212 (M ); Found: C,
4.1.9. 2-(Benzyloxy)-3-methoxybenzaldehyde (25). Yield,
+
9.13; H, 5.56. C H O requires: C, 79.25, H, 5.66;
89%; mp 58–59 ꢁC; MS (EI, 70 eV): m/z 242 (M );
1
4
12
2
UV kmax (loge): 214.0 (4.60), 252.0 (4.23), 315.0 (3.91);
IR (KBr): 1685 (C@O) cm
CDCl ): d 5.16 (s, 2H), 7.09 (d, 2H, J = 8.8 Hz), 7.35–
Found: C, 74.21; H, 5.83. C H O requires: C, 74.36;
H, 5.82; UV kmax (loge): 207.0 (4.44), 259.6 (4.42); IR
15
14
3
ꢀ
1
1
;
H NMR (200 MHz,
ꢀ
1 1
(KBr): 1693 (C@O) cm ; H NMR (200 MHz, CDCl ):
3
3
7
.47 (m, 5H), 7.85 (d, 2H, J = 8.8 Hz), 9.89 (s, 1H);
C NMR (50 MHz, CDCl ): d 70.05, 114.93, 127.26,
28.11, 128.51, 129.91, 131.78, 135.73, 163.52, 190.57.
d 3.94(s, 3H), 5.18 (s, 2H), 7.10–7.20 (m, 2H), 7.33–7.40
1
3
13
(m, 6H), 10.23 (s, 1H); C NMR (50 MHz, CDCl ): d
3
3
1
56.01, 76.28, 117.98, 118.99, 124.26, 128.53, 128.59,
1
28.67, 130.29, 136.34, 151.05, 153.06, 190.32.
8
4
.1.4. 1-[2-(Benzyloxy)phenyl]ethanone (20).
Yield,
+
7
Found: C, 79.58; H, 6.11. C H O requires: C, 79.65,
H, 6.19; UV kmax (loge): 211.0 (4.57), 246.0 (4.10),
3
(
7
2
1
1
0%; mp 41–42 ꢁC; MS (EI, 70 eV): m/z 226 (M );
4.1.10. 2-(Benzyloxy)-4-methoxybenzaldehyde
(26).
Yield, 84%; mp 65–66 ꢁC; MS (EI, 70 eV): m/z 242
1
5
14
2
+
(M ); Found: C, 74.12; H, 5.81. C H O requires: C,
15
14
3
ꢀ
1 1
05.0 (3.80); IR (KBr): 1665 (C@O) cm ; H NMR
74.36; H, 5.82; UV kmax (loge): 208.0 (4.65), 273.5
ꢀ
1 1
200 MHz, CDCl ): d 2.63 (s, 3H), 5.17 (s, 2H), 7.02–
(4.56), 312.0 (4.41); IR (KBr): 1675 (C@O) cm ; H
3
.06 (m, 2H), 7.39–7.50 (m, 6H), 7.78 (dd, 1H, J = 8.0,
NMR (200 MHz, CDCl ): d 3.85 (s, 3H), 5.17 (s, 2H),
3
1
3
.0 Hz); C NMR (50 MHz, CDCl ): d 31.98, 70.40,
6.52 (d, 1H, J = 2.2 Hz), 6.57 (dd, 1H, J = 8.6, 0.6 Hz),
7.38–7.45 (m, 5H), 7.85 (d, 1H, J = 8.6 Hz), 10.39 (s,
3
12.58, 120.66, 127.38, 128.05, 128.42, 128.51, 130.27,
33.47, 135.98, 157.82, 199.76.
1
3
1H); C NMR (50 MHz, CDCl ): d 55.40, 70.21,
3