454
P. V. Kazakov and S. N. Golosov
Amine V was synthesized as described elsewhere [2];
ane – ethyl ether system (3 : 1). The purity of fractions was
checked by TLC. Pure fractions were combined and dried
over calcined sodium sulfate. Finally, the solvent was dis-
tilled off at a reduced pressure to obtain 2.1 g (64%) of
Z -isomer IIIb.
terbinafine IIIa was obtained using an original method de-
scribed in [1].
(E )- and (Z )-1-chloro-6,6-dimethyl-2-hepten-4-ynes
(Ia, Ib). Rough 1-chloro-6,6-dimethyl-2-hepten-4-yne ob-
tained according to [4] comprising a mixture of (E )- and
(Z )-isomers, was separated by distillation at a reduced pres-
sure in a rectification column. The fraction collected at b.p.,
53 – 55°C/8 Torr contained (GC data) 95% of (Z )-1-chloro-
6,6-dimethyl-2-hepten-4-yne (Ib) and 2% of E-isomer (Ia),
while the fraction collected at b.p., 71 – 73°C/8 Torr con-
tains 95% of (E )-1-chloro-6,6-dimethyl-2-hepten-4-yne (Ia)
and 4% of Z-isomer (Ib).
1H NMR spectrum in CDCl (d, ppm): 1.34 (s, 9H,
3
C(CH ) ), 2.34 (s, 3H, CH N), 3.45 (dd, J 7.3 Hz and 1.5 Hz,
3 3
3
2H, NCH CH=), 4.0 (s, 2H, NCH C H ), 5.76 (dt, J 10.8 Hz
2
2
10
7
and 1.5 Hz, 1H, CH=CH–Cº), 6.11 (dt, J 10.8 Hz and
7.3 Hz, 1H, CH –CH=CH), 7.45 – 7.61 (m, 4H, arom H),
2
7.82 – 7.92 (m, 2H, arom H), 8.35 – 8.38 (m, 1H, arom H).
(E )-N,6,6-Trimethyl-N-(naphth-2-ylmethyl)hept-2-en-
4-yn-1-amine (VII). To a suspension of 2.7 g (0.016 mole)
of amine IV and 2.7 g (0.019 mole) of freshly calcined and
finely dispersed potassium carbonate in 20 ml of anhydrous
DMF was added with intensive stirring at room temperature
2.7 g (0.017 mole) of (E )-chloroheptenyne (Ia) in 5 ml of the
same solvent and the reaction mixture was stirred for 30 h at
20 – 22°C. Then, the suspension was poured into water
(50 ml) and extracted with carbon tetrachloride (3 ´ 50 ml).
The extracts were combined and dried over anhydrous so-
dium sulfate. The solvent were distilled off at reduced pres-
sure and the residue was purified as described above for
compound IIIb; yield of E -isomer VII, 3.9 g (74%).
Chromatographically pure N-methylnaphth-1-ylme-
thylamine (II). Rough amine II (7.3 g) synthesized accord-
ing to [2] was additionally purified by flash chromatography
in a gradient system chloroform – methanol – 25% aqueous
ammonia (10 : 1 : 0.1). the purity of fractions was checked
by TLC. Pure fractions were combined, solvents were dis-
tilled off under vacuum, and the residue was dissolved in
100 ml of diethyl ether, the solution was dried over calcined
sodium sulfate. Finally, the solvent was distilled off to obtain
6.1 g (83.6%) of chromatographically pure amine II.
1H NMR spectrum in CDCl (d, ppm): 1.45 (s, 1H,
3
H–N), 2.61 (s, 3H, CH –N), 4.25 (s, 2H, CH N), 7.47 – 7.65
1H NMR spectrum in CDCl (d, ppm): 1.27 (s, 9H,
3
2
3
(m, 4H, arom H), 7.84 – 7.88 (m, 1H, arom H), 7.93 – 7.97
(m, 1H, arom H), 8.21 – 8.25 (m, 1H, arom H)
C(CH ) ), 2.24 (s, 3H, CH N), 3.16 (dd, J 6.5 Hz and 1.3 Hz,
3 3
3
2H, NCH CH=), 3.68 (s, 2H, NCH C H ), 5.75 (dt,
N-Methylnaphth-2-ylmethylamine (IV). To a solution
of methylamine hydrochloride (1.9 g, 0.028 mole) and
triethylamine (2.85 g, 3.9 ml, 0.028 mole) in 25 ml of metha-
nol at room temperature was added a solution of 2-naphthal-
dehyde (4.0 g, 0.025 mole) in 20 ml of the same solvent and
the mixture was stirred for 8 h. To the resulting solution was
gradually added by small portions sodium borohydride
(1.1 g, 0.028 mole) and the suspension was stirred for 4 h.
Then, the solvent was distilled at a reduced pressure, the resi-
due was dissolved in 20 ml water, and the solution was triply
extracted with ethyl ether. The organic phases were com-
bined, the solvent was distilled off, and the residue was puri-
fied by flash chromatography as described above for com-
pound II. Yield of chromatographically pure amine IV, 34 g
(78%).
2
2
10
7
J 15.8 Hz and 1.3 Hz, 1H, CH=CH–Cº), 6.15 (dt, J 15.8 Hz
and 6.5 Hz, 1H, CH –CH=CH), 7.42 – 7.53 (m, 3H, arom
2
H), 7.74 (s, 1H, arom H), 7.78 – 7.86 (m, 3H, arom H).
(Z )-N,6,6-Trimethyl-N-(naphth-2-ylmethyl)hept-2-en-
4-yn-1-amine (VIII). To a suspension of 2.7 g (0.016 mole)
of amine IV and 2.7 g (0.019 mole) of freshly calcined and
finely dispersed potassium carbonate in 20 ml of anhydrous
DMF was added with intensive stirring at room temperature
2.7 g (0.017 mole) of (Z )-chloroheptenyne (Ia) in 5 ml of the
same solvent. Then, the reaction mixture was treated as de-
scribed above for compound VII; yield of Z -isomer VIII,
3.2 g (61%).
1H NMR spectrum in CDCl (d, ppm): 1.27 (s, 9H,
3
C(CH ) ), 2.29 (s, 3H, CH N), 3.32 (dd, J 6.9 Hz and 1.3 Hz,
3 3
3
1H NMR spectrum in CDCl (d, ppm): 1.72 (s, 1H, HN),
2H, NCH CH=), 3.70 (s, 2H, NCH C H ), 5.67 (dt, J
3
2
2
10
7
2.51 (s, 3H, CH N), 3.93 (s, 2H, CH N), 7.44 – 7.52 (m, 3H,
10.8 Hz and 1.3 Hz, 1H, CH=CH–Cº), 6.11 (dt, J 10.8 Hz
3
2
arom H), 7.77 (s, 1H, arom H), 7.81 – 7.87 (m, 3H, arom H).
(Z )-N,6,6-Trimethyl-N-(naphth-1-ylmethyl)hept-2-en-
4-yn-1-amine (IIIb). To a solution of 2.1 g (0.015 mole) of
potassium carbonate in 8.6 ml water was added with inten-
sive stirring 1.71 g (0.01 mole) of N-methylnaphth-1-ylme-
thylamine and 1.72 g (0.01 mole) of (Z )-chloroheptenyne
(Ib) and the mixture was stirred at 60°C for 9 h and cooled to
room temperature. The reaction mass was extracted with
benzene (3 ´ 30 ml), the organic phases were combined, and
the solvent was distilled off at reduced pressure. The residue
(2.8 g) was purified by flash chromatography in a hex-
and 6.5 Hz, 1H, CH –CH=CH), 7.42 – 7.53 (m, 3H, arom
2
H), 7.76 (s, 1H, arom H), 7.79 – 7.85 (m, 3H, arom H).
REFERENCES
1. P. V. Kazakov and S. N. Golosov, Khim.-Farm. Zh., 38(4),
34 – 36 (2004).
2. P. V. Kazakov, Khim.-Farm. Zh., 37(11), 23 – 25 (2003).
3. N. R. Chapman and Y. W. Yanas, J. Chem. Soc., No. 6,
1865 – 1868 (1953).
4. A. Stutz and G. Petranyi, J. Med. Chem., 27, 1539 – 1543 (1984).