Jul-Aug 2002
1,8-Naphthyridine-2,7-Dicarboxaldehyde into Novel 2,7-Dimethylimine Derivatives
831
to yield a tan paste that was washed with water (100 mL), fil-
tered, and dried in vacuo to yield 3.159 g (84%) of beige powder.
Recrystallization was effected from either methanol/water to
yield fluffy beige microcrystals, or hot methyl tert-butyl ether to
yield off-white needles; mp 159-160°; ir (Nujol): 2925, 2854,
(40 mL). To the stirring solution was added 1,8-naphthyridine-
2,7-dicarboxaldehyde, (0.500 g, 2.686 mmol) to produce a yel-
low solution from which a copious solid deposited within min-
utes. After 2 hours the solid was collected by filtration, washed
with methanol (10 mL), and dried in vacuo to yield off-white
microcrystalline solid 1d (0.892 g, 73%). A portion of this com-
pound was recrystallized from hot acetone to yield cream-colored
needles; mp 308-310°; ir (Nujol): 2924, 2854, 1639 (C=N), 1604,
1505, 1458, 1377, 1306, 1138, 1115, 1090, 1033, 984, 862, 816,
1642 (C=N), 1598, 1536, 1505, 1461, 1377, 1150, 1078, 958,
-1 1
888, 862, 811, 722 cm ; H nmr (CDCl ): δ 1.37-1.84 (m, 11H, -
3
CH -cyclohexyl), 8.19 (d, 1H, 3-napH, J = 8.3 Hz), 8.25 (d, 1H,
2
4-napH, J = 8.3 Hz), 8.59 (s, 1H, N=C-H); ms: (70 eV, electron
impact) m/z 348 (molecular ion), 305, 265.
-1
1
724 cm ; H nmr (CDCl ): δ 1.74 (s, 6H, -CH ), 1.86 (s, 6H, -
3
2
CH ), 2.19 (s, 3H, -CH), 8.19 (s, 1H, 3-napH, J = 8.2 Hz), 8.30
Anal. Calcd. for C
H N : C, 75.82; H, 8.10; N, 16.08.
2
22 28 4
(d, 1H, 4-napH, J = 8.2 Hz), 8.57 (s, 1H, N=C-H); ms: (70 eV,
electron impact) m/z 452 (molecular ion), 425, 135.
Found: C, 75.62; H, 8.24; N, 15.86.
(syn, syn)-2,7-Bis(N-benzylmethylimino)-1,8-naphthyridine
(1b).
Anal. Calcd. for C
H N : C, 79.61; H, 8.01; N, 12.38.
30 36 4
Found: C, 79.72; H, 7.79; N, 12.34.
In a 250 mL Erlenmeyer flask equipped with a stir bar was
charged a suspension of methanol (80 mL) and 1,8-naphthyri-
dine-2,7-dicarboxaldehyde, (3.505 g, 18.8 mmol). A solution of
benzylamine (4.096 g, 38.23 mmol) in methanol (10 mL) was
introduced in one shot, and within seconds a clear brown solution
formed. A crystalline solid precipitated within minutes, and the
reaction mixture was allowed to stir over night. Next day, a tan
solid was collected by filtration, washed with methanol (20 mL),
and air-dried to yield 4.708 g (69%) of product. A portion of this
compound was recrystallized by evaporation from acetone to
yield white needles; mp 154-155°; ir (potassium bromide): 3085,
3062, 3028, 2924, 2851, 1644 (C=N), 1602, 1580, 1495, 1452,
(syn, syn)-2,7-Bis(N-2-ethylthioethylmethylimino)-1,8-naph-
thyridine (1e).
In a 50 mL round-bottom flask equipped with a stir bar was
charged methanol (30 mL) and 1,8-naphthyridine-2,7-dicarbox-
aldehyde, (0.200 g, 1.07 mmol). To the stirring suspension was
added 2-(ethylthio)ethylamine hydrochloride (0.380 g, 2.68
mmol) followed by sodium carbonate (0.284 g; 2.68 mmol). The
mixture was stirred at room temperature for four hours, then the
solvent removed in vacuo to yield a solid yellow paste to which
was added water (20 mL) to precipitate an ecru solid; this was
allowed to air dry to furnish 0.27 g (70%) of compound 1e. A
portion of this solid was recrystallized from acetone to produce
large pale-yellow plates; mp 100-102°; ir (potassium bromide)
2990, 2910, 2724, 1647 (C=N), 1603, 1536, 1506, 1468, 1377,
-1
1
1378, 1342, 1260, 1218, 1075, 1027, 800, 752 cm ; H nmr
(CDCl ): δ 4.98 (s, 2H, -CH -), 7.36 (m, 5H, phenyl), 8.20 (d,
3
2
1H, 3-napH, J = 8.4 Hz), 8.32 (d, 1H, 4-napH, J = 8.4 Hz), 8.70
(s, 1H, N=C-H); ms: (70 eV, electron impact) m/z 364 (molecular
ion), 287, 273, 244.
-1
1
1262, 1016, 976, 924, 866, 814, 761 cm ; H nmr (CDCl ): δ
3
1.25 (t, 3H, -CH ), 2.58 (q, 2H, -CH S-), 2.91 (t, 2H, S-CH -),
3
2
2
3.95 (t, 2H, -CH N=), 8.21 (d, 1H, 3-napH), 8.25 (d, 1H, 4-
Anal. Calcd. for C
H N : C, 79.10; H, 5.53; N, 15.37.
2
24 20 4
napH), 8.59 (s, 1H, N=C-H); ms: (70 eV, electron impact) m/z
360 (molecular ion), 345, 286, 213, 157.
Found: C, 79.30; H, 5.23; N, 16.23.
(syn, syn)-2,7-Bis(N-1,1-dimethylethylmethylimino)-1,8-naph-
thyridine (1c).
Anal. Calcd. for C H N S : C, 59.96; H, 6.71; N, 15.54.
18 24
4 2
Found: C, 60.36; H, 6.90; N, 15.22.
In a 1000 mL round-bottom flask equipped with a stir bar was
charged methanol (200 mL) and 1,8-naphthyridine-2,7-dicarbox-
aldehyde, (5.550 g, 29.81 mmol). To the stirring solution was
added tert-butylamine (6.950 g, 95.03 mmol) and stirring was
maintained overnight. Next day, the solution was concentrated to
dryness to yield a microcrystalline orange solid (8.60 g). Of this,
1.27 g was dissolved in hot cyclohexane, filtered, and allowed to
cool to yield 0.89 g (68%) of white crystals upon filtration and
drying. A further 1.27 g of the crude product was heated in vacuo
to sublime a white powder (0.73 g, 56%) that was dissolved in
hot cyclohexane, and allowed to stand to yield beautiful white
crystals; mp 227-228°; ir (potassium bromide): 2923, 2854, 1646
Results and Discussion.
The synthesis of the 2,7-dimethyl-1,8-naphthyridine "synthon"
using sulfo-mix was improved in several useful ways: one was the
use of 30% oleum in the preparation of sulfo-mix as opposed to
20%, as cited previously [3]. It is found that miscibility of sulfo-
mix with water is reliably achieved within 2 hours with our
improvement, whereas the literature method with 20% oleum
appeared unpredictable, and could take up to several days. The
second improvement simply arose from our order of addition:
since the Skraup reaction classically involves conjugate bond for-
mation between aromatic amine and the alkenyl portion of croton-
aldehyde, we gave this reaction a chance to occur prior to addition
of sulfo-mix. From tlc, we observed the complete conversion of
starting 2-amino-6-methylpyridine into a highly fluorescent lower
spot within three hours at room temperature. We then added
sulfo-mix, which would presumably drive ring closure, subse-
quent loss of water, and aromatization during heating; the reaction
was then quenched over ice, and worked up to produce a crys-
talline solid after basification from which we could sublime or
recrystallize the dimethyl compound in much improved yield.
The literature [3] cites addition of crotonaldehyde to an already
formed solution of amine and sulfo-mix at 110°; in our hands this
method gave a best yield of 15%, whereas our improved method
(C=N), 1604, 1538, 1506, 1459, 1377, 1339, 1209, 1169, 1108,
-1 1
958, 906, 866, 816, 774 cm ; H nmr (CDCl ): δ 1.34 (s, 9H, -
3
C H ), 8.18 (d, 1H, 3-napH, J = 8.4 Hz), 8.27 (d, 1H, 4-napH, J =
4
9
8.4 Hz), 8.57 (s, 1H, N=C-H); ms: (70 eV, electron impact) m/z
297 (molecular ion + 1), 281, 240, 213, 157.
Anal. Calcd. for C
H N : C, 72.94; H, 8.16; N, 18.90.
18 24 4
Found: C, 72.99; H, 7.96; N, 18.76.
(syn, syn)-2,7-Bis(N-1-adamantylmethylimino)-1,8-naphthyri-
dine (1d).
In a 125 mL Erlenmeyer flask equipped with a stir bar was dis-
solved 1-adamantanamine (0.8124 g, 5.371 mmol) in methanol