M. Chhibber et al. / Bioorg. Med. Chem. 14 (2006) 8086–8098
8095
1H) 13C NMR (CDCl3): d 32.8, 117.3, 121.1, 121.4,
126.5, 128.2, 130.2, 130.7, 134.8, 143.6, 146.8, 150.5.
Anal. Calcd for C13H9Cl3O2 : C, 51.43; H, 2.99. Found:
C, 51.81; H, 3.07; Electrospray-MS: m/z 301.1 [MꢀH]+.
4.4.9. 4-(20,40-Dichlorophenoxy)-3-methoxybenzaldehyde
(8). To compound 7 (450 mg, 1.4 mmol) in H2O (10 ml)
were added K2Cr2O7 (500 mg, 1.7 mmol), Na2CO3
9.8 (br s, 1H). 13C NMR (CDCl3): d 64.4, 115.6,
118.5, 119.2, 119.7, 125.4, 128.0, 128.9, 130.3, 137.8,
142.4, 147.1, 151.2. Anal. Calcd for C13H10Cl2O3: C,
54.76; H, 3.54. Found: C, 54.63; H, 3.64; Electrospray-
MS: m/z 307.0 [M+Na]+.
4.4.13. 4-(20,40-Dichlorophenoxy)-3-methoxybenzoic acid
(12). Following the procedure detailed for 6, starting
with compound 8, compound 12 was isolated and puri-
fied using SiO2 column chromatography and solvent
(toluene/ethyl acetate = 80:20) to afford a white solid
(30 mg,
0.3 mmol)
and
18-crown-6
(7 mg,
0.02 mmol).The reaction mixture was refluxed for 8 h.
After cooling to room temperature and confirming the
completion of reaction (TLC monitoring), it was filtered
through Celite, extracted with ethyl acetate (3· 20 ml),
and dried over Na2SO4. Evaporation of the organic sol-
vent gave crude product which was purified and SiO2
column chromatography and solvent (toluene/ethyl ace-
tate = 98:02) to afford yellow oil 8 in 98% (440 mg) yield.
1H NMR (400 MHz, CDCl3): d 3.9 (s, 3H), 6.8 (d,
J = 8.0 Hz, 1H), 6.9 (d, J = 8.8 Hz, 1H), 7.2 (dd,
J = 8.8 Hz, 1H), 7.4 (dd, J = 8.0 Hz, 1H), 7.48 (d,
J = 2.4 Hz, 1H), 7.53 (d, J = 1.6 Hz, 1H). 13C NMR
(CDCl3): d 56.2, 110.9, 117.2, 121.5, 125.5, 128.2,
129.9, 130.1, 130.6, 132.8, 150.2, 150.6, 150.8, 190.7.
Anal. Calcd for C14H10Cl2O3: C, 56.59; H, 3.39. Found:
C, 56.42; H, 3.46; Electrospray-MS: m/z 319.0 [M+Na]+.
1
12 in 57.0% (120 mg, mp 146–147 ꢁC) yield. H NMR
(400 MHz, CDCl3): d 3.9 (s, 3H), 6.8 (d, J = 8.4 Hz,
1H), 6.9 (d, J = 8.8 Hz, 1H), 7.2 (dd, J = 8.4 Hz, 1H),
7.4 (d, J = 2.8 Hz, 1H), 7.7 (m, 2H), 11.6 (br s, 1H).
13C NMR (CDCl3): d 56.2, 114.2, 117.6, 121.0, 124.0,
125.3, 126.3, 128.1, 129.8, 130.5, 149.9, 150.1, 150.6,
171.4. Anal. Calcd for C14H10Cl2O3: C, 53.70; H, 3.22.
Found: C, 53.67; H, 3.29; Electrospray-MS: m/z 335.0
[M+Na]+.
4.4.14. 4-(20,40-Dichlorophenoxy)-3-hydroxybenzoicacid
(13). Following the procedure detailed for 6, starting
with compound 12, compound 13 was isolated and puri-
fied using SiO2 column chromatography and solvent
(toluene/ethyl acetate = 70:30) to afford a white solid
in 64% (mp 152–153 ꢁC) yield. 1H NMR (300 MHz,
CDCl3): d 6.8 (d, J = 8.0 Hz, 2H), 7.1 (m, 1H), 7.5 (m,
2H), 7.7 (s, 1H), 9.1 (br s, 1H). 13C NMR (CDCl3): d
118.2 (Intense), 119.1, 121.1, 124.4, 127.2, 127.6, 128.7,
129.4, 146.0, 147.3, 150.9, 168.5. Anal. Calcd for
C13H8Cl2O4: C, 52.20; H, 2.70. Found: C, 52.35; H,
2.81; Electrospray-MS: m/z 321.0 [M+Na]+.
4.4.10.
4-(20,40-Dichlorophenoxy)-3-hydroxybenzalde-
hyde (3). Following the procedure detailed for 6, com-
pound 3 was isolated and purified using SiO2 column
chromatography and solvent (toluene/ethyl ace-
tate = 95:5) to afford a white solid (mp 61–62 ꢁC) in
1
61% yield. H NMR (300 MHz, CDCl3): d 5.9 (br s,
1H), 6.7 (d, J = 8.7 Hz, 1H), 7.1 (d, J = 9.0 Hz, 1H),
7.3 (m, 2H), 7.5 (d, J = 2.7 Hz, 1H), 7.6 (d, J = 1.8 Hz,
1H), 9.9 (s, 1H). 13C NMR (CDCl3): d 115.5, 116.5,
122.7, 123.5, 127.3, 128.5, 130.9, 131.3, 132.8, 146.7,
149.1, 149.2, 190.9. Anal. Calcd for C13H8Cl2O3 : C,
55.15; H, 2.85. Found: C, 55.26; H, 2.74; HRMS: m/z
282.9928 [M+H]+. Found: 282.9937.
4.4.15.
3-Methoxy-4-(40-nitrophenoxy)-benzaldehyde
(14). Following the procedure detailed for 4, compound
14 was isolated in 90% yields. 1H NMR (300 MHz;
CDCl3) d 3.9 (s, 3H), 7.0 (d, J = 6.9 Hz, 2H), 7.2 (d,
J = 8.1 Hz, 1H), 7.5 (m, 2H), 8.2 (d, J = 6.9 Hz, 2H),
10.0 (s, 1H); 13C NMR (CDCl3) d 56.8, 111.7, 115.9,
118.8, 122.7, 124.9, 140.5, 141.8, 143.2, 151.6, 161.4,
189.7. Anal. Calcd for C14H11NO5: C, 61.54; H, 4.06;
N, 5.13. Found: C, 61.48; H, 4.16; N, 5.16; Electro-
spray-MS: m/z 296.0 [M+Na]+.
4.4.11. 4-(20,40-Dichlorophenoxy)-3-methoxybenzylalco-
hol (10). Following the procedure detailed for 5, com-
pound 10 was isolated and purified using SiO2 column
chromatography and solvent (toluene/ethyl ace-
tate = 90:10) to afford a viscous oily liquid in 77% yield.
1H NMR (300 MHz, CDCl3): d 3.8 (s, 3H), 4.6(s,
2H), 5.7 (br s, 1H), 6.7 (d, J = 8.7 Hz, 1H), 6.8 (d,
J = 8.4 Hz, 1H), 6.9 (dd, J = 8.0 Hz, 1H), 7.0 (d,
J = 1.8 Hz, 1H), 7.1 (dd, J = 8.7 Hz, 1H), 7.4 (d,
J = 2.1 Hz, 1H). 13C NMR (CDCl3): d 56.0, 64.1, 113.2,
119.0, 119.9, 121.2, 125.0, 127.7, 128.3, 130.2, 134.6,
144.6, 150.8, 151.8. Anal. Calcd for C14H12Cl2O3: C,
56.21; H, 4.04. Found: C, 56.13; H, 3.96; Electrospray-
MS: m/z 321.1 [M+Na]+.
4.4.16. 3-Methoxy-4-(40-nitrophenoxy) benzyl alcohol
(15). Following the procedure detailed for 5, compound
15 was isolated in 91% (99–100 ꢁC) yield. 1H NMR
(300 MHz; CDCl3) d 3.8 (s, 3H), 4.7 (s, 1H), 6.9 (m,
3H), 7.1 (m, 2H), 8.2 (d, J = 8.1 Hz, 2H), 11.9 (br s,
1H) 13C NMR (CDCl3) d 55.8, 64.8, 111.7, 115.7,
119.6, 122.4, 125.7, 139.8, 141.9, 142.3, 151.6, 163.5.
Anal. Calcd for C14H13NO5: C, 61.09; H, 4.76; N,
5.09. Found: C, 61.12; H, 4.81; N, 5.11; Electrospray-
MS: m/z 298.0 [M+Na]+.
4.4.12. 4-(20,40-Dichlorophenoxy)-3-hydroxybenzylalco-
hol (11). Following the procedure detailed for 6, com-
pound 11 was isolated and purified using SiO2 column
chromatography and solvent (toluene/ethyl ace-
tate = 90:10) to afford a viscous oily liquid in 52%
yield. 1H NMR (300 MHz, CDCl3): d 4.5 (s, 2H),
6.7(d, J = 8.7 Hz, 1H), 6.8–6.9 (m, 1H), 7.0 (d,
J = 8.0 Hz, 1H), 7.1 (m, 2H), 7.4 (d, J = 2.0 Hz, 1H),
4.4.17. 3-Methoxy-4-phenoxy benzyl alcohol (16). To a
suspension of compound 2 (4.5 g, 16.3 mmol) in reflux-
ing H2O (100 ml) were added Fe (9.1 g, 162.9 mmol)
and FeSO4Æ7H2O (9.0 g, 32.4 mmol). The reaction mix-
ture was refluxed for 8 h. After cooling to room temper-
ature, it was filtered through Celite, washed thoroughly
with CH2Cl2, and dried over Na2SO4. The evaporation