Reaction of perfluorocarboxylic anhydrides with 2-(4-chlorophenyl)-1-(3,4- dimethoxyphenyl)-8,9-dimethoxypyrrolo[2,1-a]isoquinoline [6]

Full text of DOI:10.1134/S1070363207020247

ISSN 1070-3632, Russian Journal of General Chemistry, 2007, Vol. 77, No. 2, pp. 319 320.
Original Russian Text A.E. Krivoshein, D.V. Krivorotov, M.V. Vorob’ev, M.L. Petrov, V.A. Polukeev, 2007, published in Zhurnal Obshchei Khimii,
2007, Vol. 77, No. 2, pp. 347 348.
Pleiades Publishing, Ltd., 2007.
LETTERS
TO THE EDITOR
Reaction of Perfluorocarboxylic Anhydrides
with 2-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-8,9-di-
methoxypyrrolo[2,1-a]isoquinoline
A. E. Krivosheina, D. V. Krivorotova, M. V. Vorob’eva,
M. L. Petrova, and V. A. Polukeevb
a St. Petersburg State Institute of Technology,
Moskovskii pr. 26, St. Petersburg, 190013 Russia
e-mail: den@orgchem.spb.ru
b Vekton Ltd., St. Petersburg, Russia
Received July 6, 2006
DOI: 10.1134/S1070363207020247
In the recent years, pyrrolo[2,1-a]isoquinolines of
the papaverine series attract attention as potential
biologically active substances [1 3]. Syntheses of
these compounds are based on reaction of papaverine
with -halo carbonyl compounds [1 4]; depending
on the structure of the latter, different substituents can
be introduced into positions 2 and 3 of the pyrrolo-
[2,1-a]isoquinoline molecule [1, 3, 4]. Despite ap-
parent simplicity of that synthetic approach, we pro-
pose an alternative route to the preparation of hitherto
unknown 3-perfluoroacylpyrrolo[2,1-a]isoquinolines
of the papaverine series via acylation of 2-(4-chloro-
phenyl)-1-(3,4-dimethoxyphenyl)-8,9-dimethoxypyr-
rolo[2,1-a]isoquinoline (I, pyrrolo[2,1-a]papaverine)
[4] with perfluorinated carboxylic anhydrides. As the
latter we used trifluoroacetic and perfluorosuccinic
anhydrides. We have found that the reaction of I with
perfluorocarboxylic anhydrides in N,N-dimethylform-
amide at room temperature is complete in several
hours to give 1-[2-(4-chlorophenyl)-1-(3,4-dimethoxy-
phenyl)-8,9-dimethoxypyrrolo[2,1-a]isoquinolin3-yl]-
2,2,2-trifluoroethan-1-one (IIa) and 4-[2-(4-chloro-
phenyl)-1-(3,4-dimethoxyphenyl)-8,9-dimethoxypyr-
rolo[2,1-a]isoquinolin-3-yl]-2,2,3,3-tetrafluoro-4-
oxobutanoic acid (IIb), respectively, in excellent yield.
Alkaline cleavage of trifluoroacetyl derivative
IIa (like haloform reaction) recovered initial pyrrolo-
[2,1-a]papaverine I, presumably as a result of de-
carboxylation of intermediate pyrrolo[2,1-a]isoquino-
lin-3-carboxylic acid.
O
O
CF3
MeO
MeO
O
;
F
O
O
O
CF3
N
N
MeO
MeO
MeO
R
O
MeO
NaOH, R = CF3
MeO
Cl
MeO
Cl
I
IIa, IIb
R = CF3 (a), CF2CF2COOH (b).
Thus we have demonstrated the possibility for fun-
ctionalization of pyrrolo[2,1-a]isoquinolines of the
papaverine series at the 3 position with perfluorocar-
boxylic anhydrides. It should be emphasized that the
synthesis of compounds IIa and IIb according to the
known schemes [1 4] would require difficultly ac-
319

320
KRIVOSHEIN et al.
cessible and unstable (under the reaction conditions)
2-bromo-1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-
dione and 5-bromo-6-(4-chlorophenyl)-2,2,3,3-tetra-
fluoro-4,6-dioxohexanoic acid, respectively.
(3C, OCH3), 105.09 (1C), 106.42 (1C), 109.16,
117.82, 122.94 (2C, CF2CF2), 110.92 (1C), 113.99
(1C), 114.31 (1C), 118.57 (1C), 121.70 (1C), 123.75
(1C), 123.99 (1C), 126.01 (1C), 126.66 (1C), 126.87
(2C), 131.99 (3C), 133.18 (1C), 134.31 (1C), 137.41
(1C), 148.22 (1C), 148.68 (1C), 149.19 (1C), 150.70
(1C), 158.84 (1C, COOH), 175.39 (1C, C=O). 19F
NMR spectrum, F, ppm: 120.51 s (2F, CF2),
110.67 s (2F, CF2). Found, %: C 59.32; H 4.05;
N 2.55. C32H24ClF4NO7. Calculated, %: C 59.50, H
3.74; N 2.17.
Reactions of 2-(4-chlorophenyl)-1-(3,4-dime-
thoxyphenyl)-8,9-dimethoxypyrrolo[2,1-a]isoquino-
line (I) with trifluoroacetic and tetrafluorosuccinic
anhydrides. The corresponding perfluorinated an-
hydride, 0.012 mol, was added under stirring (using a
magnetic stirrer) to a solution of 0.01 mol of 2-(4-chlo-
rophenyl)-1-(3,4-dimethoxyphenyl)-8,9-dimethoxy-
pyrrolo[2,1-a]isoquinoline (I) [4] in 20 ml of anhyd-
rous DMF. The mixture was stirred for 2 h under
argon and poured into 400 ml of water, and the pre-
cipitate was filtered off.
Reaction of 1-[2-(4-chlorophenyl)-1-(3,4-di-
methoxyphenyl)-8,9-dimethoxypyrrolo[2,1-a]iso-
quinolin-3-yl]-2,2,2-trifluoroethan-1-one (IIa) with
a solution of sodium hydroxide. Compound IIa,
0.01 mol, was added to a mixture of 100 ml of water,
200 ml of alcohol, and 0.10 mol of sodium hydroxide.
The mixture was stirred for 24 h at 70 C, and the
colorless precipitate was filtered off and recrystallized
from acetonitrile. We thus isolated compound I in
95% yield, mp 191 192 C [4].
1-[2-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-
8,9-dimethoxypyrrolo[2,1-a]isoquinolin-3-yl]-2,2,2-
trifluoroethan-1-one (IIa). Yield 95%, mp 245
1
247 C (from toluene). H NMR spectrum, , ppm:
3.30 s (3H, OCH3), 3.65 s (3H, OCH3), 3.76 s (3H,
OCH3), 3.91 s (3H, OCH3), 6.76 m (2H, Harom),
6.91 m (2H, Harom), 7.24 m (4H, Harom), 7.36 s (1H,
Harom), 7.42 d (1H, Harom, J 7 Hz), 9.55 d (1H,
Harom, J 7 Hz). 13C NMR spectrum, C, ppm: 54.88
(1C, OCH3), 55.58 (3C, OCH3), 104.96 (1C), 106.39
(1C), 110.80 (1C), 114.18 (1C), 114.31 (1C), 116.87
(1C), 118.46 (1C), 121.64 (1C), 123.64 (2C), 125.86
(1C), 126.47 (1C), 126.82 (2C), 131.94 (3C), 133.23
(1C), 134.15 (1C), 137.63 (1C), 148.25 (1C), 148.68
(1C), 149.22 (1C), 150.65 (1C), 113.55 119.30 127.79
128.62 (1C, CF3), 169.54 d.d (1C, C=O). 19F NMR
spectrum, F, ppm: 68.62 s (3F, CF3). Found, %:
C 63.32; H 4.00; N 2.45. C30H23ClF3NO5. Calculated,
%: C 63.22; H 4.07; N 2.46.
1
The H, 13C, and 19F NMR spectra were recorded
from 1% solutions in DMSO-d6 on a Bruker AM-500
1
spectrometer (500 MHz for H and 125 MHz for 13C
and 19F). The elemental compositions were deter-
mined on a Perkin Elmer 240 analyzer. The melting
points were measured on an NMK Kofler hot stage.
The progress of reactions was monitored by TLC on
Silufol UV-254 plates using hexane acetone diethyl
ether (10:2:1) as eluent.
REFERENCES
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4-[2-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-
8,9-dimethoxypyrrolo[2,1-a]isoquinolin-3-yl]-2,2,
3,3-tetrafluoro-4-oxobutanoic acid (IIb). Yield 73%,
2. Mamyrbekova, Zh.A., Soldatova, S.A., Abelentsev, V.I.,
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1
mp 140 142 C (from diethyl ether). H NMR spec-
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3.75 s (3H, OCH3), 3.89 s (3H, OCH3), 4.39 s (1H,
OH), 6.76 d (1H, Harom, J 8 Hz), 6.81 s (1H, Harom),
6.85 s (1H, Harom), 6.92 d (1H, Harom, J 8 Hz),
7.25 d.d (4H, Harom), 7.35 s (1H, Harom), 7.39 d (1H,
Harom, J 8 Hz), 9.38 d (1H, Harom, J 8 Hz). 13C
NMR spectrum, C, ppm: 54.96 (1C, OCH3), 55.63
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RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 77 No. 2 2007