Reaction of indigo malonic ester with dimethyl sulfate

Full text of DOI:10.1134/S1070428012080179

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 8, pp. 1131−1132. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.N. Andin, A.D. Sokolov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 8, pp. 1131−1132.
SHORT
COMMUNICATIONS
Reaction of Indigo Malonic Ester with Dimethyl Sulfate
A. N. Andin and A. D. Sokolov
Far-Eastern State University, Vladivostok, 690950 Russia
e-mail: andin@chem.dvgu.ru
Received November 26, 2010
DOI: 10.1134/S1070428012080179
Indigo malonic ester (I), the product of indigo conden-
sation with malonic ester, a representative of the class of
6,13-dioxopyrido[1,2-a;3,4-b]diindoles, has been known
since the beginning of the previous century; it has been
first obtained in 1926 alongside the product of indigo
condensation with phenylacetic acid and its N-acyl de-
rivatives [1]. The chemical properties of these compounds
were not practically further examined. Yet the pyrido[1,2-
a;3,4-b]diindole system is the structural skeleton of a
series of marine alkaloids of a high biological action, e.g.,
fascaplysin from the sponge Fascaplysinopsis sp. [2].
tially presumed that the indigo malonic ester being an
ambidente nucleophile would form a mixture of N- and
O-methylation products. However unexpectedly along-
side the product of the N-methylation II we isolated
a substituted pyrido[3,4-b]indole III (Scheme 1).
We failed to convert fully compound II into III, and
increasing the reaction duration and the excess of di-
methyl sulfate did not affect the yield of compound III.
The sequence of transformations leading to compound
III may be rationalize as follows. Evidently first the am-
bidente anion originating from initial pyridodiindole I at
the action of sodium hydride suffers the O-methylation.
The product of the О-methylation in the presence of ex-
cess dimethyl sulfate is methylated again at the nitrogen
We examined the reaction of indigo malonic ester
(I) with dimethyl sulfate. The reaction was carried out
in DMF in the presence of sodium hydride. It was ini-
Scheme 1.
O
O
O
O
O
O
EtO
EtO
EtO
N
N
N
Me2SO4, NaH
DMF
+
N
N
N
O
H
O
O
OMe
Me
II
Me
III
I
Scheme 2.
O
O
O
O
O
O
EtO
EtO
EtO
N
N
N
OH _
_H+
Me2SO4
Me2SO4
I
III
N
N+
Me
N
_O
OMe
OMe
OMe
Me
1131

ANDIN, SOKOLOV
1132
Scheme 3.
N+
N+
O
N+
O
N
Cl _
Cl _
N
N
O_
H
O
H
H
OMe
IV
V
VI
atom forming a quaternary salt. At further quenching of
the reaction mixture with water a hydroxide anion adds to
the cation followed by the cleavage of the С13–С13а bond
and the formation of the final product III (Scheme 2).
III was extracted with ethyl acetate (2 × 30 ml), the
extracts were washed with water, dried with anhydrous
sodium sulfate, the solvent was distilled off, the residue
was washed with cold ethanol. Yield 0.07 g (31%).
Yellow-orange crystals, mp 217–218°С. IR spectrum
(KBr), ν, cm–1: 1728 (COOEt), 1707 (COOMe), 1669
(С=О of α-pyridone). 1Н NMR spectrum (CDCl3), δ,
ppm: 1.44 t (3Н, СН3, J 7.1 Hz), 3.59 s (3Н, NCH3), 3.72 s
This result demonstrates the fundamental possibility to
pass virtually in two stages from indigo to the functional
derivatives of the marine alkaloid reticulatine (IV) iso-
lated from the sponge Fascaplysinopsis reticulata [3].An
analogous opening of the five-membered ring was earlier
described in the literature. It was shown that fascaplysin
(V) at treatment with alkali formed zwitter-ion VI [4]
(Scheme 3).
(3Н, ОСН3), 4.54 q (2Н, СН2, J 7.1 Hz), 7.11 t (1Нarom
J 7.6 Hz), 7.17 d (1Нarom, J 8.3 Hz), 7.41 d (1Нarom
,
,
J 7.7 Hz), 7.49 s (1Н, СН), 7.56 t (1Нarom, J 7 Hz),
7.57 t (1Нarom, J 7.1 Hz), 7.70 t (1Нarom, J 7.4 Hz), 8.13 d
(2Нarom, J 7.9 Hz). 13С NMR spectrum (CDCl3), δ, ppm:
14.7, 29.7, 52.8, 61.9, 108.8, 113.2, 118.7, 119.2, 119.7,
126.5, 128.1, 129.0, 129.2, 129.4, 131.8, 132.0, 133.8,
137.9, 141.7, 147.6, 158.4, 165.6, 167.2. Mass spectrum:
m/z 405 [M + H]+. Found, %: С 68.10; H 5.13; N 7.02.
C23H20N2O5. Calculated, %: С 68.31; H 4.98; N 6.93.
M 404.42.
Ethyl 12-methyl-6,13-dioxo-12,13-dihydro-6Н-
pyrido[1,2-a;3,4-b]diindole-7-carboxylate (II). In 4 ml
of anhydrous DMF was dissolved at stirring 0.2 g (0.56
mmol) of compound I, 0.04 g (1.67 mmol) of sodium
hydride was added, the mixture was stirred for 10 min and
afterwards a solution of 0.3 ml (3.17 mmol) of dimethyl
sulfate in 1 ml of DMF was added, and the strring at room
temperature was continued for 10 min more. The reaction
mixture was poured into 100 ml of diluted water solution
of NaCl, the precipitate was filtered off and dried. Yield
0.09 g (43%). Red-violet crystals, mp 257–258°С. IR
spectrum (KBr), ν, cm–1: 1722 (COOEt), 1639 (С=О of
IR spectra were recorded from pellets with KBr on a
spectrophotometer Perkin Elmer Spectrum BX. 1Н NMR
spectra were registered on a spectrometer BrukerAC-400
(operating frequency 400 MHz). Internal reference TMS.
Mass spectra were taken on a GC-MS instrument Agi-
lent 1200 Series LC/MSD (chemical ionization mode),
column Zorbax XDB C18, 2.1 × 150 mm, grains of
sorbent 3.5 μm, eluent methanol–water, 70:30, detector
temperature 50°С. The reaction progress was monitored
by TLC on Sorbfil plates, eluent ethyl acetate.
1
α-pyridone), 1604 (С=О). Н NMR spectrum (DMSO-
d6), δ, ppm: 1.26 t (3Н, СН3, J 7.1 Hz), 3.60 s (3Н,
NCH3), 4.17 q (2Н, СН2, J 7.1 Hz), 7.23 t (1Н, Нarom
,
J 7.6 Hz), 7.40–7.48 m (2Нarom), 7.60–7.68 m (2Нarom),
7.75 t (1Нarom, J 7.6 Hz), 7.97 d (1Нarom, J 7.3 Hz), 8.61 d
(1Нarom, J 7.9 Hz). 13С NMR spectrum (DMSO-d6), δ,
ppm: 14.8, 35.1, 63.0, 111.7, 118.1, 118.5, 118.9, 120.3,
122.8, 124.5, 124.7, 125.1, 127.5, 127.6, 134.0, 137.0,
141.1, 146.3, 146.7, 150.8, 163.5, 185.8. Mass spectrum:
m/z 373 [M + H]+. Found, %: С 70.73; H 4.53; N 7.64.
C22H16N2O4. Calculated, %: С 70.96; H 4.33; N 7.52.
M 372.38.
REFERENCES
1. Posner, T., Ber., 1926, vol. 59, p. 1814.
2. Roll, D.M., Ireland, C.M., Lu, H.S., and Clardy, J., J. Org.
Chem. 1988, vol. 53, p. 3276.
3. Jimenez, C., Quinoa, E., and Crews P., Tetrahedron Lett.
1991, vol. 32, p. 1843.
4. Fretz, H., Ucci-Stoll, K., Hug, P., Schoepfer, J., and Lang,
M., Helv. Chim. Acta. 2001, vol. 84, p. 867.
Ethyl 2-(2-carbomethoxyphenyl)-9-methyl-3-oxo-
2,3-dihydro-9Н-pyrido[3,4-b]-indole-4-carboxylate
(III). Filtrate obtained after the precipitation of compound
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 8 2012