Synthesis, Antiproliferative and Pro-Apoptotic Effects
Medicinal Chemistry, 2018, Vol. 14, No. 2 185
precipitate was washed with acetic acid (20 mL, 10%) and
water (20 mL). The product was then recrystallised from
methanol.
2.12. General Procedure 11: Preparation of 3-nitro-2-
phenyl-1,2-dihydroquinolines (148, 149)
To a mixture of 2-aminobenzaldehyde (1.2 mmol) and
the appropriate (E)-(2-nitrovinyl)benzene (1 mmol) (1 mmol,
0.149 g) in benzene (5 mL) was added DABCO (0.5 mmol,
56 mg) at room temperature. The reaction mixture was re-
2.14.1. 1-(4-Chloro-2-hydroxyphenyl)-3-(4-chlorophenyl)-
3-hydroxyprop-2-en-1-one (163)
o
Yield: 0.489 g (20%), Mp 154-157 C. IR
ꢁ
(film):
o
3078 (C-H), 1688 (C=C), 1594 (C=O), 1488 (C=Cm)a,x780 (C-
fluxed at 100 C for 10 h. The reaction was cooled and ex-
tracted with DCM (20 mL) and washed with 10 % HCl (2 x
5 mL). The organic extracts were washed with water and
brine, then dried over anhydrous Na2SO4, and solvent re-
moved in vacuo. The residue was purified by flash column
chromatography over silica gel (eluent: dichloromethane-
hexane, 3:1) and recrystallised from ethanol.
1
Cl). H NMR (400 MHz, DMSO-d6) ꢀ6.75 (s, 1 H, =CH),
6.92 (dd, 1 H, ArH, H5), 7.29 (s, 1 H, ArH, H3), 7.49 (d, 2
H, J = 8 Hz, 2 x ArH, H3’ & H5’), 7.71 (d, 1 H, J = 8 Hz,
ArH, H6), 7.89 (d, 2 H, J = 8.5 Hz, 2 x ArH, H2’ & H6’),
12.23 (s, 1 H, phenol OH), 15.42 (s, 1 H, enol OH). 13C
NMR (101 MHz, CDCl3) ppm 92.2 (=CH), 118.9, 119.8,
128.2, 128.4, 128.9, 129.2, 129.5, 131.7, 131.8, 138.9
(C4’/C4), 141.8 (C4’/C4), 163.2 (C2), 176.4 (C=C(OH)),
194.8 (CO). HRMS: calculated for C15H9Cl2O3 [M+-H]
306.9929: found 306.9931.
2.12.1. 4-(3-Nitro-1,2-dihydroquinolin-2-yl)phenol (149)
o
117 mg (40%), Mp 207-209 C, purple crystals, IR ꢁ
(KBr): 3356 (OH), 2917 (CH), 1603 (C=C), 1492, 13m3a5x
1
(NO2) cm-1. H NMR (400 MHz, DMSO-d6) ꢀ5.84 (s, 1 H,
H2), 6.53-6.58 (m, 2 H, 2 x ArH), 6.69 (d, J = 8.6 Hz, 2 H, 2
x ArH), 7.10-7.14 (m, 3 H, 3 x ArH), 7.31 (d, J = 7.5 Hz, 1
H, 1 x ArH), 8.15 (s, 1 H, H4), 9.48 (s, 1 H, OH). 13C NMR
(101 MHz, DMSO-d6) ppm 53.5 (C2), 113.3, 114.1, 115.3,
116.8, 127.3, 131.5, 131.9, 133.7, 134.2, 139.5 (C3), 145.7
(C8a), 157.4 (C4’). HRMS: calculated for C15H12N2O3Na
[M++Na] 291.0746: found 291.0736.
2.15. General Procedure 14: Preparation of 3-
nitroflavones (179-188)
To the appropriately substituted flavone (1.58 mmol) was
added of ammonium nitrate (5 mmol, 400 mg) followed by
dry dichloromethane (25 mL) and dry acetonitrile (25 mL).
Trifluoroacetic acid (8.49 mmol (1.2 mL) was then added
with cooling in an ice bath. The reaction mixture was heated
to 40 oC and allowed to react for 1.5 hours. The mixture was
neutralised with water (100 mL), extracted with dichloro-
methane(2 x 20 mL). The solvent was removed in vacuo and
the 3-nitroflavone was recrystallised from methanol.
2.13. General Procedure 12: Preparation of o-benzo-
yloxyacetophenones (152-160)
The appropriately substituted o-hydroxyacetophenone
(11.7 mmol, 2 g) was added to a solution of 4-chlorobenzoyl
chloride (16.4 mmol, 2.866 g) and pyridine (4 mL) and the
mixture was stirred for 30 min. The reaction mixture was
poured onto 100 mL of 1 M hydrochloric acid and 50 g of
crushed ice. The product was then filtered and washed with
water (20 mL) and ice-cold methanol (20 mL). The product
was then recrystallised from methanol.
2.15.1. 7-Chloro-2-(4-chlorophenyl)-3-nitrochromen-4-one
(181)
o
Yield: 109 mg (33%), Mp 197-199 C. IR
ꢁ
(KBr):
3068 (C-H), 1660 (C=O), 1613 (C=C), 1599 (Nm-Oax), 1426
(C=C), 794 (C-Cl) cm-1. H NMR (400 MHz, DMSO-d6)
1
ꢀ7.51-7.58 (m, 3 H, 3 x ArH, H3’ H5’ & H6), 7.66-7.71 (m,
3 H, 3 x ArH, H2’, H6’ & H8), 8.27 (d, 1 H, J = 8 Hz, ArH,
H5). 13C NMR (101 MHz, CDCl3) ppm 118.1 (C7), 121.4,
125.9, 127.1, 127.4, 128.7 (C3’ & C5’), 129.4 (C2’ & C6’),
139.4, 141.2 (C3), 154.9 (C8a), 158.9 (C2), 167.5 (C4).
HRMS: calculated for C15H7Cl3NO4 [M++Cl] 369.9441:
found 369.9428. 3-Nitro-2-(3,4,5-trimethoxy-2-nitrophenyl)
chromen-4-one (185) was obtained as a minor product , 36
mg (7%). IR ꢁmax (film): 2947 (C-H), 1671 (C=O), 1532 (N-
2.13.1. 4-Chlorobenzoic Acid 2-acetyl-5-chlorophenyl Ester
(155)
Yield: 2.93 g (76%), Mp 93-95 oC, colourless crystals. IR
ꢁ
max
(film): 3095 (CH), 1741 (C=O), 1595 (C=C), 1261 (C-
1
O), 752 (C-Cl) cm-1. H NMR (400 MHz, DMSO-d6) ꢀ 2.54
(s, 3 H, CH3), 7.29 (s, 1 H, ArH, H3), 7.38(d, 1 H, J = 8 Hz,
ArH, H5), 7.53 (d, 2 H, J = 8.5 Hz, 2 x ArH, H3’, H5’), 7.84
(d, 1 H, J = 8.5 Hz, ArH, H6), 8.14 (d, 2 H, J = 8 Hz, 2 x
ArH, H2’, H6’). 13C NMR (101 MHz, CDCl3) ppm 29.1
(CH3), 124.1, 126.2, 126.9, 128.4, 128.7, 128.8, 131.0,
131.3, 138.7 (C4’), 140.2 (C4), 149.4 (C2), 163.6(CO-O),
195.7(CO). HRMS: calculated for C15H10Cl2O3Na [M++Na]
330.9905: found 330.9904.
1
O), 1464 (C=C), 1375 (C-O) cm-1. H NMR (400 MHz,
DMSO-d6) ꢀ3.95 (s, 3 H, OCH3), 4.02 (s, 3 H, OCH3), 4.10
(s, 3 H, OCH3) 6.92 (s, 1 H, ArH, H6’), 7.49 (d, 1 H, J = 8.5
Hz, ArH, H8), 7.53-7.56 (m, 1 H, ArH, H6), 7.78-7.84 (m, 1
H, ArH, H7), 8.31(d, 1 H, J = 7.5 Hz, ArH, H5). 13C NMR
(101 MHz, CDCl3) ppm 55.9 (2 x OCH3 on C3’ & C5’), 60.6
(OCH3 on C4’), 106.9, 117.5, 117.9 (C7), 123.1, 126.1,
126.4, 135.1, 145.6 (C3), 147.9, 154.8 (C8a), 155.3, 156.7
(C2), 167.9 (CO). HRMS: calculated for C18H14N2O9Na
[M++Na] 425.0597: found 425.0583.
2.14. General Procedure 13: Preparation of 3-hydroxy-3-
phenylprop-2-en-1-ones (161-169)
The appropriately substituted o-benzoyloxyacetophenone
(15.8 mmol) was dissolved in dry pyridine (15 mL) in a
o
2.16. X-Ray Crystallography
pressure flask and heated to 50 C. Potassium hydroxide (25
o
mmol, 1.42 g), (powdered and preheated at 100 C), was
Data for samples 35, 54, 68, 94 and 118 were collected
on a Bruker APEX DUO using Mo Kꢀ radiation (ꢁ =
0.71073 Å) using a Mitegen cryoloop and at 100(2) K (Ox-
ford Cobra Cryosystem). Bruker APEX [22] software was
o
then added and the mixture was heated at 50 C for 20 min.
The reaction mixture was then cooled and acidified with
acetic acid (21 mL, 10%). The mixture was then filtered and