Pozharskii et al.
first yellow fraction was bromide 10 eluted as yellowish oil,
191 mg (94%). The product has spectral properties identical to those
reported in refs 7 and 10.
1,8-Bis(dimethylamino)-2-formylnaphthalene (4g). Yellow oil.
1H NMR (250 MHz, CDCl3): δ 2.77 (6H, s), 3.22 (6H, s), 7.01
(1H, dd, J ) 7.3, 1.2 Hz), 7.35 (5H, m), 7.67 (1H, d, J ) 8.5 Hz),
10.22 (1H, d, J ) 0.8 Hz). Anal. Calcd for C15H18N2O: C, 74.36;
H, 7.51; N, 11.58. Found: C, 74.42; H, 7.43; N, 11.52.
2-Benzoyl-1,8-bis(dimethylamino)naphthalene (4i). Brown-
yellow oil. 1H NMR (250 MHz, CDCl3): δ 2.66 (6H, s), 2.75 (6H,
s), 7.00 (1H, dd, J ) 6.4, 2.3 Hz), 7.25 (1H, d, J ) 8.5 Hz), 7.35-
7.43 (5H, m), 7.52 (1H, t, J ) 6.6 Hz), 7.67 (2H, m). Anal. Calcd
for C16H20N2O: C, 74.91; H, 7.86; N, 10.93. Found: C, 74.97; H,
7.82; N, 11.02.
General Procedures for Preparation of Ortho-mono- and
-disubstituted 1,8-Bis(dimethylamino)naphthalenes 4a-i. (A)
Organometallic Synthesis. The corresponding electrophile was
added to a solution of monolithium derivative prepared from 300
mg of 10 and BunLi (0.64 mL, 1 mmol) under Ar and at -20 °C.
The resulting mixture was kept at -20 °C for 30 min, allowed to
warm to rt, and poured into water. The ethereal layer was separated,
and the aqueous layer was extracted with Et2O (3 × 5 mL). The
combined organic extracts were evaporated, and the residue was
purified by PTLC on Al2O3 to give the desired compounds with
the yields indicated in Table 1.
B. LAH Reduction of ortho-Aldehydes and ortho-Ketones.
An 8-fold excess of a powdered LiAlH4 was added over a period
of 15 min by small portions to a solution of the corresponding
carbonyl derivative in dry Et2O or THF (10 mL). The mixture was
stirred at rt for 12 h and then quenched with water (5 mL). The
precipitate was filtered and washed with Et2O (3 × 5 mL). The
solvent was removed, and the residue was purified by PTLC on
Al2O3.
1,8-Bis(dimethylamino)-2,7-di(hydroxymethyl)naphthalene (5a).
Reduction of 5f (method B) gave 5a (90%) as yellow crystals, mp
113-114 °C (MeCN). 1H NMR (300 MHz, CDCl3): δ 2.95 (12H,
s), 4.85 (4H, s), 7.44 (2H, d, J ) 8.4 Hz), 7.57 (2H, d, J ) 8.4
1
Hz). H NMR (250 MHz, DMSO-d6): δ 2.89 (12H, s), 4.63 (4H,
d, J ) 5.6 Hz), 5.14 (2H, t, J ) 5.6 Hz), 7.51 (2H, d, J ) 8.5 Hz),
7.57 (2H, d, J ) 8.5 Hz). Anal. Calcd for C16H22N2O2: C, 70.07;
H, 8.03; N, 10.22. Found: C, 70.13; H, 8.09; N, 10.14.
1,8-Bis(dimethylamino)-2,7-di(r-hydroxyethyl)naphthalene (5b).
Pale-yellow crystals with mp 226-227 °C (acetone). 1H NMR (250
MHz, DMSO-d6): δ 1.38 (6H, m), 2.90 (12H, s), 5.01 (2H, m,
J ) 4.4 Hz), 5.11 (2H, m), 7.51 (2H, d, J ) 8.4 Hz), 7.61 (2H, d,
J ) 8.4 Hz). Anal. Calcd for C18H26N2O2: C, 71.49; H, 8.67; N,
9.26. Found: C, 71.57; H, 8.72; N, 9.19.
1,8-Bis(dimethylamino)-2-hydroxymethylnaphthalene (4a).
Reduction of 4g (method B) gave 4a (90%) as light-yellow oil. 1H
NMR (300 MHz, CDCl3): δ 2.74 (6H, s), 3.0 (6H, s), 4.87 (2H,
s), 7.13 (1H, dd, J ) 7.0, 0.8 Hz), 7.30 (1H, t, J ) 7.7 Hz), 7.39
(1H, d, J ) 8.4 Hz), 7.43 (1H, dd, J ) 7.6, 0.8 Hz), 7.52 (1H, d,
Reduction of ketone 5g (method B) gave 69% of alcohol 5b,
which was identical in its properties to the sample synthesized
according to method A.
1
J ) 8.4 Hz). H NMR (300 MHz, DMSO-d6): δ 2.67 (6H, s),
2.89 (6H, s), 4.62 (2H, d, J ) 5.6 Hz), 5.1 (1H, t, J ) 5.6 Hz),
7.01 (1H, d, J ) 7.3 Hz), 7.24 (1H, t, J ) 7.7 Hz), 7.38 (1H, d,
J ) 7.9 Hz), 7.46 (1H, d, J ) 8.4 Hz), 7.51 (1H, d, J ) 8.5 Hz).
Anal. Calcd for C15H20N2O: C, 73.74; H, 8.25; N, 11.47. Found:
C, 73.78; H, 8.21; N, 11.35.
1,8-Bis(dimethylamino)-2,7-di(r-hydroxybenzyl)naphtha-
lene (5c). Pale-yellow crystals with mp 190-191 °C (MeCN). 1H
NMR (250 MHz, CDCl3): δ 2.96 (12H, s), 6.30 (2H, s), 7.29-
1
7.40 (12H, m), 7.56 (2H, d, J ) 8.5 Hz). H NMR (250 MHz,
DMSO-d6): δ 2.98 (12H, s), 5.79 (2H, d, J ) 4.5 Hz), 6.13 (2H,
d, J ) 4.5 Hz), 7.21 (2H, d, J ) 8.4 Hz), 7.27-7.32 (10H, m),
7.56 (2H, d, J ) 8.4 Hz). Anal. Calcd for C28H30N2O2‚1/2MeCN:
C, 77.91; H, 7.10; N, 7.83. Found: C, 78.06; H, 7.12; N, 7.62.
Reduction of ketone 5h (method B) gave 73% of alcohol 5c,
which had properties identical to those of the pattern synthesized
according to method A.
1,8-Bis(dimethylamino)-2-(r-hydroxyethyl)naphthalene (4b).
Colorless crystalline powder with mp 54-56 °C (acetone). 1H NMR
(250 MHz, CDCl3): δ 1.57 (3H, d, J ) 6.3 Hz), 2.63 (3H, s), 2.78
(3H, s), 2.99 (6H, s), 5.35 (1H, q, J ) 6.3), 7.19 (1H, d, J ) 7.3
Hz), 7.30 (1H, t, J ) 7.7 Hz), 7.46 (1H, d, J ) 7.7 Hz), 7.50 (1H,
1
d, J ) 8.4 Hz), 7.57 (1H, d, J ) 8.4 Hz). H NMR (250 MHz,
DMSO-d6): δ 1.33 (3H, d, J ) 6.5 Hz), 2.68 (6H, br s), 2.90 (6H,
s), 5.00 (1H, d, J ) 3.9 Hz), 5.18 (1H, m), 7.12 (1H, d, J ) 6.8
Hz), 7.26 (1H, t, J ) 7.6 Hz), 7.42 (1H, d, J ) 6.8 Hz), 7.53 (1H,
d, J ) 8.4 Hz), 7.57 (1H, d, J ) 8.4 Hz). Anal. Calcd for
C16H22N2O: C, 74.38; H, 8.58; N, 10.84. Found: C, 74.27; H, 8.51;
N, 10.90.
1,8-Bis(dimethylamino)-2,7-di(r-hydroxyisopropyl)naphtha-
lene (5d). Light-beige crystals with mp 123-125 °C (acetone). 1H
NMR (300 MHz, CDCl3): δ 1.76 (12H, s), 2.91 (12H, s), 6.19
1
(2H, s), 7.37 (2H, d, J ) 8.7 Hz), 7.48 (2H, d, J ) 8.7 Hz). H
NMR (250 MHz, DMSO-d6): δ 1.63 (12H, s), 2.82 (12H, s), 6.72
(2H, s), 7.45 (2H, d, J ) 8.6 Hz), 7.51 (2H, d, J ) 8.6 Hz). Anal.
Calcd for C20H30N2O2: C, 72.73; H, 9.09; N, 8.48. Found: C, 72.79;
H, 9.18; N, 8.40.
LAH reduction of ketone 4h (method B) gave 74% of alcohol
4b, which was identical in properties to the pattern synthesized
according to method A.
The second yellow fraction gave 1,8-bis(dimethylamino)-2-(R-
1,8-Bis(dimethylamino)-2-(r-hydroxybenzyl)naphthalene (4c).
1
1
hydroxyisopropyl)-naphthalene (4d) as a brownish-yellow oil. H
Brownish-yellow oil. H NMR (250 MHz, CDCl3): δ 2.65 (3H,
NMR (250 MHz, CDCl3): δ 1.67 (6H, s), 2.67 (6H, s), 2.94 (6H,
s), 7.32-7.43 (3H, m), 7.53-7.60 (2H, m), 10.72 (1H, s). 1H NMR
(250 MHz, DMSO-d6): δ 1.59 (6H, s), 2.64 (6H, s), 2.84 (6H, s),
7.36-7.48 (2H, m), 7.56-7.71 (3H, m), 8.46 (1H, s). Anal. Calcd
for C17H24N2O: C, 74.96; H, 8.88; N, 10.28. Found: C, 75.00; H,
8.83; N, 10.32.
s), 2.72 (3H, s), 2.85 (6H, s), 6.25 (1H, s), 7.16-7.54 (10H, m).
1H NMR (250 MHz, DMSO-d6): δ 2.61 (3H, s), 2.75 (3H, s), 2.85
(6H, s), 5.75 (1H, d, J ) 4.5 Hz), 6.16 (1H, d, J ) 4.5 Hz), 7.12-
7.19 (2H, m), 7.25-7.32 (5H, m), 7.41-7.52 (3H, m). Anal. Calcd
for C21H24N2O: C, 78.71; H, 7.55; N, 8.74. Found: C, 78.79; H,
7.52; N, 8.67.
1,8-Bis(dimethylamino)-2,7-diformylnaphthalene (5f). Orange-
yellow crystals with mp 78-79 °C (CHCl3). 1H NMR (300 MHz,
CDCl3): δ 3.17 (12H, s), 7.10 (2H, d, J ) 8.4 Hz), 7.67 (2H, d,
J ) 8.4 Hz), 9.97 (2H, s). Anal. Calcd for C16H18N2O2: C, 71.11;
H, 6.69; N, 10.38. Found: C, 71.03; H, 6.74; N, 10.36.
The second yellow fraction gave 1,8-bis(dimethylamino)-2-
formylnaphthalene (4g) as a yellow oil, identical in properties to
the aldehyde described above.
2,7-Diacetyl-1,8-bis(dimethylamino)naphthalene (5g). Pale-
yellow crystals with mp 116-117 °C (CHCl3). 1H NMR (250 MHz,
CDCl3): δ 2.52 (6H, s), 2.93 (12H, s), 7.23 (2H, d, J ) 8.3 Hz),
7.32 (2H, d, J ) 8.3 Hz). Anal. Calcd for C18H22N2O2: C, 72.46;
H, 7.43; N, 9.39. Found: C, 72.35; H, 7.49; N, 9.32.
Reduction of ketone 4i (method B) gave 71% of alcohol 4c,
which was identical in properties to the compound synthesized
according to method A.
1,8-Bis(dimethylamino)-2-(r-hydroxy-r-phenylethyl)naph-
thalene (4f). Colorless crystals with mp 191-193 °C (CHCl3). 1H
NMR (300 MHz, CDCl3): δ 1.93 (3H, s), 2.24 (3H, s), 2.4 (3H,
s), 2.62 (3H, s), 2.83 (3H, s), 7.14-7.47 (7H, m), 7.57 (1H, dd,
J ) 7.7, 1.5 Hz), 7.68 (2H, br s), 9.55 (1H, s). 1H NMR (250 MHz,
DMSO-d6): δ 1.8 (3H, s), 2.3 (3H, s), 2.36 (6H, br s), 2.67 (3H,
s), 7.10-7.41 (7H, m), 7.62 (1H, dd, J ) 7.5, 1.7 Hz), 7.72 (1H,
d, J ) 8.6), 7.77 (1H, d, J ) 8.9 Hz), 8.07 (1H, s). Anal. Calcd for
C22H26N2O: C, 79.04; H, 7.78; N, 8.38. Found: C, 79.12; H, 7.71;
N, 8.30.
3018 J. Org. Chem., Vol. 72, No. 8, 2007