Synthesis and Reactions of Some Heterocyclic Azacyanines
J . Org. Chem., Vol. 66, No. 4, 2001 1315
nines with base was employed with azacyanine 9a (400 mg,
6.68 mmol) was dissolved in 20 mL of a 10% methanolic KOH
solution and 2 mL of water, and a white precipitate formed
immediately. After 1 h of stirring, the solids were collected by
1
0 mmol) for 4 h to produce 12 as white needles (290 mg, 9.49
1
3 2
mmol, 99%): mp 193-195 °C; H NMR (300 MHz, CD CO D)
δ 6.60 (s, 2H), 6.91 (d, J ) 8 Hz, 1H), 7.34 (d, J ) 8 Hz, 1H),
filtration, washed with CH
white needles (260 mg, 0.57 mmol, 86%): mp 250-251 °C; H
NMR (400 MHz, CD CO D) δ 6.57 (s, 2H), 7.70 (m, 1H), 7.89
(m, 1H), 7.92 (m, 2H), 8.09 (m, 1H), 8.15 (m, 1H), 8.27 (s, 1H),
2 2
Cl , and dried to produce 15 as
1
7
1
.65 (m, 2H), 7.81 (m, 3H), 7.96 (m, 2H), 8.11 (d, J ) 8 Hz,
13
H), 8.43 (d, J ) 8 Hz, 1H), 8.52 d, J ) 8 Hz, 1H); C NMR
CO D) δ 61.0, 109.9, 113.6, 118.7, 124.9, 125.7,
3
2
(75 MHz, CD
3
2
1
3
1
1
1
26.9, 128.0, 128.0, 128.1, 129.7, 130.4, 131.8, 134.2, 135.5,
36.4, 137.6, 155.2, 164.1; IR (neat) 3310, 1653, 1624, 1331,
8.48 (d, J ) 8 Hz, 1H), 8.52 (s, 1H), 8.61 (d, J ) 8 Hz, 1H);
C
NMR (100 MHz, CD CO D) δ 64.0, 103.0, 107.2, 119.3, 125.4,
3
2
-
1
146, 752 cm . Anal. Calcd for C19
H
15
N
3
O; C, 75.73; H, 5.02;
126.3, 126.8, 127.1, 128.8, 129.1, 130.5, 131.5, 132.5, 134.9,
135.0, 136.0, 136.5, 151.2, 163.5; IR (neat) 3300, 1650, 1612,
N, 13.94. Found: C, 75.62; H, 5.03; N, 13.90.
-Br om o-1-(5-br om o-2-im in o-3-m eth yl-2H-p yr id in -1-yl-
-
1
5
1099, 916 cm ; UV-vis λmax/nm (log ꢀ) (methanol) 293 (3.97).
m eth yl)-3-m eth yl-1H-p yr id in -2-on e (13d ). The general pro-
cedure for the reaction of azacyanines with base was employed
with azacyanine 7d (0.429 g, 0.863 mmol). The mixture was
Anal. Calcd for C19 O: C, 50.03; H, 2.85; N, 9.15.
2 3
H13Br N
Found: C, 50.41; H, 2.99; N, 9.04.
9-Meth oxypypr idin -4-on e-6H-pyr ido[6,1-a :2′,1′-d][1,3,5]-
tr ia zin e (20). Haloazacyanine 14c (300 mg, 1.08 mmol) was
dissolved in 50 mL of a 10% methanolic KOH and 5 mL of
water and refluxed for 12 h. The solution was diluted with
warmed for 4 h to produce 13d as white crystals (230 mg, 590
1
mmol, 69%): mp 239-242 °C; H NMR (400 MHz, CD
3
CO
2
D):
δ 2.15 (s, 3H), 2.31 (s, 3H), 6.41 (s, 2H), 7.55 (s, 1H), 7.82(s,
H), 8.21 (s, 1H), 8.51 (s, 1H); 13C NMR (100 MHz, CD
CO D): δ 16.2, 16.9, 64.7, 101.3, 105.8, 126.7, 131.9, 135.2,
37.5, 142.9, 144.8, 153.9, 163.1; IR (neat) 3400, 1660, 1645,
1
3
-
water (50 mL) and extracted with CH
2
Cl
2
(4 × 10 mL). The
2
organic solution was dried (Na SO ), filtered, and evaporated
2
4
1
1
2
by rotatory evaporation. Purification by column chromatog-
raphy (10% MeOH; EtOAC) produced 20 as a clear oil (30 mg,
-
1
573, 1330, 1139, 886 cm ; UV-vis λmax/nm (log ꢀ) (CH
3
CO
2
H)
1
66 (2.67), 310 (3.91). Anal. Calcd for C13 O; C, 40.34;
H
13Br
2
N
3
0.13 mmol, 12%): H NMR (300 MHz, CDCl
3
) δ 3.70 (s, 3H),
H, 3.39; N, 10.86. Found: C, 39.96; H, 3.34; N, 10.57.
Gen er a l Meth od for th e Rea ction of Ha loa za cya n in es
5.84 (s, 2H), 5.87 (d, J ) 7 Hz, 1H), 6.12 (d, J ) 9 Hz, 1H),
6.66 (d, J ) 3 Hz, 1H), 6.83 (d, J ) 10 Hz, 1H), 7.17 (dd, J )
7
b,c,d w ith Ba se. The haloazacyanine (0.5-2.0 g scale) was
10, 3 Hz, 1H), 7.31 (m, 1H); 13C NMR (75 MHz, CDCl
) δ 56.4,
3
mixed with 10% methanolic KOH (20 mL containing 2 mL of
water). The slurry was magnetically stirred at room temper-
ature, and formation of the orange product with disappearance
of the highly fluorescent starting material were monitored by
TLC (7:3 MeOH: EtOAc). The reaction is normally finished
within 2 h, however, warming the alcoholic solution (50 °C)
leads to product in 5-10 min. The solution is diluted with
57.1, 98.1, 110.2, 114.8, 123.4, 133.7, 139.1, 142.4, 147.7, 148.9,
-
1
161.6; IR (neat) 1637, 1579, 1497, 778 cm
.
9-P h en ylp yr d in -4-on e-6H -p yr id o[6,1-a :2′,1′-d ][1,3,5]-
tr ia zin e (21). A 250 mL round-bottom flask equipped with a
magnetic stir bar was charged with halo-azacyanine 14c (40
mg, 0.14 mmol), DME (10 mL), phenylboronic acid (140 mg,
1.2 mmol), Pd(PPh
2 M K CO . This solution was slowly refluxed for 2 h and
quenched with 5 mL or water. The organic layer was sepa-
rated, dried with Na SO , filtered, concentrated, and purified
3 4
) (90 mg, 0.081 mmol), and 0.70 mL of a
water (80 mL) and extracted with CH
2
Cl
2
(4 × 10 mL). The
2
3
yellow orange CH Cl solution is dried (Na
2
2
2
SO ), filtered, and
4
evaporated to give an orange solid which was recrystallized
from ethyl acetate.
2
4
by flash column chromatography (20% methanol in ethyl
9
-Ch lor op yr id in -4-on e-6H -p yr id o[6,1-a :2′,1′-d ][1,3,5]-
acetate) to afford 21 as red needles (25 mg, 0.091 mmol, 65%):
1
tr ia zin e (14b). The general procedure for the reaction of
haloazacyanines with base was employed with azacyanine 7b
1 g, 2.63 mmol; 2 d) to produce 14b (200 mg, 860 mmol, 33%):
R
f
) 0.35; H NMR (300 MHz, CDCl
3
) δ 5.92 (s, 2H), 6.17 (d,
J ) 9 Hz, 1H), 6.90 (d, J ) 9 Hz, 1H), 7.39 (m, 8H), 7.59 (dd,
J ) 9, 2 Hz, 1H); 13C NMR (75 MHz, CDCl
) δ 56.6, 98.5, 110.7,
122.1, 124.9, 125.6, 128.3, 129.3, 129.3, 131.63 135.0, 138.2,
(
R
(
6
3
1
f
) 0.25; mp 257-258 °C; H NMR (300 MHz, CDCl
3
) δ 5.80
-1
s, 2H), 5.91, (dd, J ) 8, 1 Hz, 1H), 6.19 (dd, J ) 9, 1 Hz, 1H),
142.2, 150.0, 161.5; IR (neat) 1643, 1558, 1498, 1477, 758 cm .
1
3
.75 (d, J ) 9 Hz, 1H), 7.27 (m, 3H); C NMR (75 MHz, CDCl
3
)
3,9-Dip h en yl-6H-d ip yr id o[1,2-a :2′,1′-d ][1,3,5]tr ia zin -5-
iu m (22). Azacyanine 7c (90 mg, 0.2 mmol) was dissolved in
DME (10 mL), phenylboronic acid (280 mg, 2.4 mmol), Pd-
δ 56.3, 98.9, 111.8, 117.2, 123.1, 131.9, 139.2, 142.2, 147.0,
49.3, 161.3; IR (neat) 1641, 1550, 1495, 1137, 769 cm-1. Anal.
Calcd for C11 ClN O; C, 56.54; H, 3.45; N, 17.98. Found: C,
6.34; H, 3.48; N, 17.60.
-Br om op yp r id in -4-on e-6H-p yr id o[6,1-a :2′,1′-d ][1,3,5]-
1
H
8
3
(PPh
This solution was refluxed for 4h and quenched with 5 mL or
water. The organic layer was, separated, dried with Na
filtered, and concentrated. The solid was washed with CH
Cl and acetone to produce 22 (60 mg, 0.13 mmol 68%): mp
3 4 2 3
) (180 mg, 0.162 mmol), and 1.40 mL of a 2 M K CO .
5
9
2
SO4,
tr ia zin e (14c). The general procedure for the reaction of halo-
azacyanines with base was employed with azacyanine 7c (1.80
g, 3.84 mmol; 12 h), and flash column chromatography (20%
methanol in ethyl acetate) afforded 14c as orange crystals (840
mg, 3.0 mmol, 79%): mp 261-263 °C; H NMR (300 MHz,
CDCl
Hz, 1H), 6.71 (d, J ) 10 Hz, 1H), 7.23 (m, 3H); C NMR (75
MHz, CDCl ) δ 56.2, 98.9, 102.8, 111.9, 123.3, 134.1, 141.1,
42.1, 147.0, 149.3, 161.3; IR (neat) 1635, 1564, 1490, 1134,
2
-
2
1
361-363 °C; H NMR (400 MHz, DMSO-d ) δ 6.52 (s, 2H), 7.34
6
(d, J ) 9 Hz, 2H), 7.44 (m, 2H), 7.53 (m, 4H), 7.74 (m, 4H),
1
13
8.38 (dd, J ) 9, 2 Hz, 2H), 8.52 (d, J ) 2 Hz, 2H); C NMR
3
) δ 5.78 (s, 2H), 5.87 (d, J ) 8 Hz, 1H), 6.17 (d, J ) 9
6
(100 MHz, DMSO-d ) δ 65.9, 122.0, 126.8, 129.0, 129.5, 130.1,
1
3
134.7, 135.8, 142.5, 151.0; IR (neat) 1532, 1480, 1330, 1318,
-
1
1
3
823 cm . Anal. Calcd for C23
N, 8.90. Found: C, 58.52; H, 3.93; N, 8.71.
H
18IN
3
2 2
‚ / H O C, 58.49; H, 4.05;
1
7
(
-
1
76 cm ; UV-vis λmax/nm (log ꢀ) (methanol) 281 (4.07), 358
BrN O: C, 47.51; H,
.90; N, 15.11. Found: C, 47.64; H, 2.97; N, 15.10.
-Br om o-1,11-d im eth yl-p yp r id in -4-on e-6H-p yr id o[6,1-
4.14), 436 (4.18). Anal. Calcd for C11
H
8
3
Ack n ow led gm en t. We are grateful to the Cystic
Fibrosis Foundation and the National Science Founda-
tion for financial support of this research. The 400 and
2
9
a :2′,1′-d ][1,3,5]tr ia zin e (14d ). The general procedure for the
reaction of haloazacyanines with base was employed with
azacyanine 7d (0.429 g, 0.863 mmol). The mixture was refluxed
until the solution turned colored and purified by flash column
3
00 MHz NMR spectrometers used in this study were
funded in part by a grant from NSF (CHE-9808183).
M.J .H. is grateful to the American University of Beirut
for a Sabbatical leave at the University of California,
Davis.
chromatography (30% methanol in ethyl acetate) to afford 14d
1
as a colorless oil (50 mg, 0.20 mmol, 19%): R
300 MHz, CDCl
.92 (d, J ) 7 Hz, 1H), 7.17 (m, 3H); 13C NMR (75 MHz, CDCl
δ 17.0, 17.8, 56.8, 99.0, 101.9, 121.3, 131.7, 132.4, 138.3, 139.9,
45.1, 148.8, 161.3; IR (neat) 1635, 1558, 1491, 777 cm-1
-Br om o-2-(4-b r om o-1-im in o-3-1H -isoq u in olin -2-yl-
m eth yl)-2H-isoqu in olin -1-on e (15). Azacyanine 9b (380 mg,
f
) 0.35; H NMR
(
5
3
) δ 2.09 (s, 3H), 2.19 (s, 3H), 5.77 (s, 2H),
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR,
3
)
13
1
C NMR, and IR for compound 11/14d /21 and H NMR and
IR for compound 20. This material is available free of charge
via the Internet at http://pubs.acs.org.
1
.
4
J O001484K