Thiocarbamoylation of 1,3,3-trimethyl-3,4-dihydroisoquinolines with benzoyl isothiocyanate

Full text of DOI:10.1134/S1070428015120349

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 12, pp. 1818–1819. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © A.G. Mikhailovskii, A.S. Yusov, O.V. Gashkova, 2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 12,
pp. 1851–1852.
SHORT
COMMUNICATIONS
Thiocarbamoylation of 1,3,3-Trimethyl-3,4-dihydroisoquinolines
with Benzoyl Isothiocyanate
A. G. Mikhailovskii, A. S. Yusov, and O. V. Gashkova
Perm State Pharmaceutical Academy, ul. Polevaya 2, Perm, 614090 Russia
e-mail: neorghim@pfa.ru
Received September 23, 2015
DOI: 10.1134/S1070428015120349
We previously studied reactions of enamines of the
,3-dialkyl-1,2,3,4-tetrahydroisoquinoline series with
N-[2-(3,3-Dimethyl-3,4-dihydroisoquinolin-1-yl)-
1-sulfanylideneethyl]benzamide (3). A solution of
1.2 mL (10 mmol) of benzoyl chloride in 15 mL of
acetone was added dropwise to a solution of 0.78 g
(10 mmol) of ammonium thiocyanate in 30 mL of hot
acetone, and the resulting suspension was added to
a solution of 1.73 g (10 mmol) of enamine 1 in 15 mL
of acetone. The mixture instantaneously turned yellow
and was cooled to 20°C and diluted with 200 mL of ice
water. An oily material separated and slowly crystal-
lized on cooling to ~0°C. The precipitate was filtered
off, dried, and recrystallized from propan-2-ol. Yield
3
phenyl isothiocyanate [1]. Reactions of these sub-
strates with acyl isothiocyanates have not been report-
ed so far. It is known that aroyl isothiocyanates can be
generated in situ from the corresponding aroyl chloride
and ammonium thiocyanate [2]. Aroyl isothiocyanates
are more reactive electrophiles than aryl isothiocya-
nates, and enamines 1 and 2 [3, 4] reacted with ben-
zoyl isothiocyanate in acetone at 20°C almost instanta-
neously with formation of compounds 3, 4.
Unlike enamino thioamides synthesized previously
2
.09 g (62%), yellow crystals, mp 211–213°C. IR
[
1], compounds 3 and 4 in solution exist as imino
–
1
1
spectrum, ν, cm : 3450 (NH, amide), 3275 (NH,
chelate), 1675 (C=O), 1615 (C=N). H NMR spectrum,
tautomers. Their H NMR spectra contained a singlet
1
from protons in the exocyclic CH group (δ 3.28 ppm)
2
δ, ppm: 1.33 s (6H, CH ), 2.95 s (2H, 4-H), 3.28 s (2H,
and two singlets at δ 9.96, 13.19 (3) and 9.51,
3.29 ppm (4) due to NH and SH protons of the two
tautomers. Thioamide–iminothiol tautomerism is typi-
cal of thioamides [5]; it is favored by the presence of
electron-withdrawing benzoyl group, which increases
the acidity of the NH proton.
3
1
1
-CH ), 7.33–7.91 m (9H, Harom), 9.96 (0.5H, NH),
3.19 s (0.5H, SH). Found, %: C 71.18; H 5.78;
1
2
N 8.42; S 9.35. C H N OS. Calculated, %: C 71.40;
20 20
2
H 5.99; N 8.33; S 9.53.
N-[2-(2,2-Dimethyl-1,2-dihydrobenzo[f]isoquin-
olin-4-yl)-1-sulfanylideneethyl]benzamide (4) was
synthesized in a similar way from 2.23 g (10 mmol) of
compound 2. Yield 2.32 g (60%), yellow crystals,
N-Benzoyl thioamides 3 and 4 attract interest as
intermediate products and potential biologically active
substances.
Me
Me
N
Me
Me
R
Me
Me
·
H
R
··
N
PhC(O)Cl, NH NCS
R
R
4
S
S
O
O
N
N
N
R
R
Ph
Ph
H
Me
, 2
1
3, 4
1
, 3, R = H; 2, 4, RR = benzo.
1
818

THIOCARBAMOYLATION OF 1,3,3-TRIMETHYL-3,4-DIHYDROISOQUINOLINES
1819
–
1
mp 151–153°C. IR spectrum, ν, cm : 3450 (NH,
REFERENCES
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1
1
. Surikova, O.V. and Mikhailovskii, A.G., Russ. J. Org.
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H NMR spectrum, δ, ppm: 1.53 s (6H, CH ), 3.05 s
3
(
2H, 1-H), 3.28 s (2H, 4-CH ), 7.51–8.23 m (11H,
2
Harom), 9.51 (0.5H, NH), 13.29 s (0.5H, SH). Found,
: C 74.47; H 5.63; N 7.34; S 8.24. C H N OS.
Calculated, %: C 74.58; H 5.74; N 7.25; S 8.30.
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%
2
4
22
2
1
The H NMR spectra were recorded on a Bruker-
3
. Shklyaev, V.S., Aleksandrov, B.B., Legotkina, G.I.,
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Chem. Heterocycl. Compd., 1983, vol. 19, p. 1242.
3
00 spectrometer (300 MHz) using DMSO-d as
6
solvent and HMDS as internal standard (δ 0.05 ppm).
The IR spectra were measured on a Specord M-80
spectrometer from solutions in chloroform. The purity
of the isolated compounds was checked by TLC on
Silufol UV-254 plates using acetone–ethanol–chloro-
form (1:3:6) as eluent; spots were visualized under
UV light or by treatment with iodine vapor.
4
5
. Aleksandrov, B.B., Shklyaev, V.S., and Shklyaev, Yu.V.,
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RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 12 2015