organic phase was dried (Na2SO4) and concentrated. The residue
was purified by flash chromatography on silica gel (hexane/EtOAc
= 2/1) to afford 2 as a yellow solid (1.07 g, 80%). m.p: 96–98 ◦C;
IR (KBr, cm-1) 1664; 1H NMR (CDCl3, 300 MHz, 298 K) d 10.85
(1H, d, J = 3.3 Hz), 9.18 (1H, dd, J = 9.3, 2.7 Hz), 7.98–7.91
(2H, m), 7.66 (1H, ddd, J = 9.3, 4.8, 2.2 Hz), 7.33 (1H, dd, J = 9.2,
4.6 Hz), 4.06 (3H, s); 13C NMR (CDCl3, 75 MHz, 298 K) d 191.8,
164.1, 136.66, 133.1, 130.2, 130.1, 129.9, 127.1, 118.7, 116.8, 113.9,
56.8; MS (ESI): m/z 265.8.
further stirred for 8 h. The reaction mixture was diluted with
dichloromethane (100 mL), partitioned in 2% aqueous NaHCO3
solution (10 mL) and water. The organic layer was washed with
brine, dried over Na2SO4, and concentrated under reduced pres-
sure. The residue was purified by flash column chromatography
on silica gel (CH2Cl2/MeOH = 19/1) to afford 1 as a white solid
(153 mg, 40%). mp: 154–158 ◦C; IR (KBr, cm-1): 2223; 1H NMR
(CDCl3, 300 MHz, 298 K) d 8.62–8.59 (2H, m), 8.11 (1H, d, J =
1.5 Hz), 7.98 (1H, d, J = 8.9 Hz), 7.74 (1H, d, J = 8.9 Hz), 7.67 (2H,
doublet of triplet, J = 5.9, 1.8 Hz), 7.54 (1H, dd, J = 8.8, 1.7 Hz),
7.35 (1H, s), 7.32 (2H, d, J = 3.2 Hz), 7.28 (1H, s), 7.24–7.2 (2H,
m), 4.26 (2H, s), 3.91 (4H, s); 13C NMR (CDCl3, 75 MHz, 298 K) d
159.2, 157.7, 149.0, 137.2, 135.8, 134.8, 130.3, 127.6, 127.1, 123.8,
123.3, 122.7, 121.9, 120, 114.3, 105.6, 58.9, 50.3; HRMS FAB-(+):
m/z calcd for C24H21ON4 (M+): 381.1715, found. 381.1716.
5-Formyl-6-methoxynaphthalene-2-carbonitrile (3)
To a solution of compound 2 (532 mg, 2 mmol) in anhydrous
NMP (15 mL) was added copper(I) cyanide (269 mg, 3 mmol)
under argon. The mixture was heated at 135 ◦C for 8 h. After being
cooled to room temperature, the reaction mixture was poured into
an aqueous NH4Cl solution (25 mL), and it was stirred at room
temperature for 1 h. The mixture was then partitioned between
EtOAc and water. The organic layer was washed with brine and
dried over Na2SO4. Removal of the solvent under reduced pressure,
and the residue was purified by flash column chromatography on
silica gel (hexane/EtOAc = 1/1) to afford the desired compound 3
as a yellow solid (253 mg, 60%). mp: 234–238 ◦C; IR (KBr, cm-1):
2229, 1659; 1H NMR (DMSO-d6, 300 MHz, 298 K) d 10.73 (1H,
s), 9.18 (1H, d, J = 8.9 Hz), 8.58 (1H, s), 8.41 (1H, d, J = 9.2
Hz), 7.91 (1H, d, J = 8.9 Hz), 7.78 (1H, d, J = 9.2 Hz), 4.11 (3H,
s); 13C NMR (DMSO-d6, 75 MHz, 298 K) d 191, 165.8, 138.4,
134.7, 132.5, 130.1, 126.9, 125.1, 118.9, 115.8, 115.2, 106.8, 57.2;
HRMS FAB-(+): m/z calcd for C13H9O2N (M+): 211.0633, found
211.0634.
5-[(Bis-pyridin-2-ylmethyl-amino)-methyl]-6-methoxy-
naphthalene-2-carbonitrile (5)
Bis-(2-pyridylmethyl)amine (144 mL, 0.8 mmol) was added drop-
wise to a solution of 3 (211 mg, 1 mmol) in anhydrous CH2Cl2
(10 mL). The mixture was stirred for 2 h before treatment with
NaBH(OAc)3 (466 mg, 2.2 mmol), which was further stirred
for 8 h. The reaction mixture was diluted with dichloromethane
(80 mL), partitioned with 2% aqueous NaHCO3 solution (8 mL)
and water. The organic layer was washed with brine, dried
over Na2SO4, and concentrated under reduced pressure. The
residue was purified by flash column chromatography on silica
gel (CH2Cl2/MeOH = 20/1) to afford 8 as a yellow solid (217 mg,
55%). mp: 175–178 ◦C; IR (KBr, cm-1): 2222; 1H NMR (CDCl3,
300 MHz, 298 K) d 8.52–8.49 (2H, m), 8.09–8.06 (2H, m), 7.75
(1H, d, J = 9 Hz), 7.57 (2H, doublet of triplet, J = 7.8, 1.8 Hz),
7.48 (1H, dd, J = 9, 1.8 Hz), 7.33–7.26 (3H, m), 7.13 (1H, dd, J =
5.1, 1.2 Hz), 7.1 (1H, dd, J = 5.1, 1.2 Hz), 4.15 (2H, s), 3.95 (3H, s),
3.83 (4H, s); 13C NMR (CDCl3, 75 MHz, 298 K) d 160, 158.3, 149,
136.3, 135.9, 134.4, 130.3, 127.9, 126.5, 126.3, 123.5, 122.1, 120,
119.8, 114.4, 106.6, 61, 56.5, 48.4; HRMS FAB-(+): m/z calcd for
C25H22ON4 (M+): 394.4684, found. 394.4681.
5-Formyl-6-hydroxynaphthalene-2-carbonitrile (4)
To a solution of compound 3 (422 mg, 2 mmol) in anhydrous
CH2Cl2 (20 mL) was added dropwise 1.0 M BBr3 in CH2Cl2 (3 mL,
◦
3 mmol) at 0 C under argon. The resulting mixture was stirred
at 0 ◦C for 1 h, and then the temperature was raised to room
temperature and it was further stirred for 8 h. To the mixture at
0
◦C was added a 5% aqueous NaHCO3 solution (10 mL), and
then the mixture was warmed to room temperature with stirring
for 30 min and then partitioned between CH2Cl2 and water. The
organic layer was washed with brine, dried over Na2SO4, and
concentrated under reduced pressure. The residue was purified
by flash column chromatography on silica gel (hexane/CH2Cl2 =
1/9) to afford 4 as a yellow solid (217 mg, 55%). mp: 217–220 ◦C;
IR (KBr, cm-1): 2225, 1630; 1H NMR (CD2Cl2, 300 MHz, 298 K)
d 13.34 (1H, d, J = 3.3 Hz), 10.8 (1H, d, J = 3.2 Hz), 8.46 (1H,
d, J = 8.8 Hz), 8.2 (1H, s), 8.06 (1H, d, J = 9.2 Hz), 7.79 (1H,
dd, J = 8.8, 1.5 Hz), 7.28 (1H, d, J = 9.2 Hz); 13C NMR (CD2Cl2,
75 MHz, 298 K) d 193.8, 167.3, 139.4, 135.5, 135.4, 130.6, 127.4,
121.8, 120.6, 119.1, 111.8, 108.7; HRMS FAB-(+): m/z calcd for
C12H8O2N (M+): 197.0477, found 197.0476.
1·Zn(II)
To a solution of DPA 1 (57.2 mg, 0.15 mmol) in MeOH (5 mL) was
added Zn(NO3)2·6H2O (44.6 mg, 0.15 mmol), and the resulting
mixture was stirred overnight. Solvent was removed under vacuum
and the obtained sticky solid was recrystallized twice from
MeOH/CH2Cl2 (9/1) to give the complex 1·Zn(II) as white solid
(54 mg, 81%). 1H NMR (CD3OD, 300 MHz, 298 K) d 8.63 (2H,
d, J = 4.5 Hz), 8.24 (1H, d, J = 9 Hz), 8.08 (1H, d, J = 1.5 Hz), 7.80
(2H, dt, J = 7.8, 1.8 Hz), 7.65 (1H, dd, J = 9, 1.8 Hz), 7.55 (1H, d, J
= 9 Hz), 7.48–7.43 (2H, m), 7.12 (1H, d, J = 7.8 Hz), 6.87 (1H, d, J
= 1.5 Hz), 4.34, 4.16 (2 ¥ 2H, AB type, J = 16.2 Hz), 4.23 (2H, s);13C
NMR (CD3OD, 75 MHz, 298 K) d 156.7, 149.4, 142.2, 137, 136.1,
133, 129.2, 129, 126.3, 125.1, 124.4, 121.2, 120.2, 115.4, 107.6, 60.2,
51; HRMS FAB-(+): m/z calcd for C24H19ON4Zn (M+): 443.0850,
found 443.0853.
5-{[Bis(pyridin-2-ylmethyl)amino]methyl}-6-hydroxy-
naphthalene-2-carbonitrile (1)
Bis(2-pyridylmethyl)amine (144 mL, 0.8 mmol) was added drop-
wise to a solution of 4 (197 mg, 1 mmol) in anhydrous CH2Cl2
(10 mL). The mixture was stirred for 2 h before NaBH(OAc)3
(699 mg, 3.3 mmol) was added, and the resulting mixture was
1·Cu(II)
This copper(II) complex was prepared similarly as above by
addition of Cu(NO3)2·2.5H2O to a solution of DPA 1 in MeOH at
7778 | Org. Biomol. Chem., 2011, 9, 7774–7779
This journal is
The Royal Society of Chemistry 2011
©