New iodo- and nitro-substituted pyrroles

Article abstract of DOI:10.1007/s11178-006-0013-0

Treating 2,5-dimethyl-4-ethoxycarbonyl- and 2,5-dimethyl-4-carboxypyrroles with iodine furnished 3-iodo-2,5-dimethyl-4-ethoxycarbonyl- and 3,4-diiodo-2,5-dimethylpyrroles. It was established that 3-iodo-2,5-dimethyl-4- ethoxycarbonylpyrrole reacted at heating with silver nitrite to afford 2,5-dimethyl-3-nitro-4-ethoxycarbonylpyrrole, and the same reagent oxidized 3,4-diiodo-2,5-dimethylpyrrole to give 3,4-diiodo-2-methyl-5-formylpyrrole. 2005 Pleiades Publishing, Inc.

Full text of DOI:10.1007/s11178-006-0013-0

Russian Journal of Organic Chemistry, Vol. 41, No. 11, 2005, pp. 1654-1656. Translated from Zhurnal Organicheskoi Khimii, Vol. 41, No. 11, 2005,
pp. 1688-1690.
Original Russian Text Copyright Ó 2005 by Mironov, Kharitonova, Efimkin, Solomentseva.
.
New Iodo- and Nitro-substituted Pyrroles
A.F. Mironov, O.V. Kharitonova, A.G. Efimkin, and T.A. Solomentseva
Lomonosov Moscow State Academy of Fine Chemical Processing, Moscow, 119571Russia
e-mail: httos.mitht@g23.relcom.ru
Received November 29, 2004
Abstract—Treating 2,5-dimethyl-4-ethoxycarbonyl- and 2,5-dimethyl-4-carboxypyrroles with iodine furnished 3-
iodo-2,5-dimethyl-4-ethoxycarbonyl- and 3,4-diiodo-2,5-dimethylpyrroles. It was established that 3-iodo-2,5-
dimethyl-4-ethoxycarbonylpyrrole reacted at heating with silver nitrite to afford 2,5-dimethyl-3-nitro-4-
ethoxycarbonylpyrrole, and the same reagent oxidized 3,4-diiodo-2,5-dimethylpyrrole to give 3,4-diiodo-2-methyl-
5-formylpyrrole.
Historically, the majority of investigations on the
porphyrin chemistry have been dedicated to the study,
synthesis, and evaluation of the biochemical character-
istics of the natural tetrapyrrole pigments (heme, chloro-
phyll), but in the last two decades considerable interest is
aroused by syntheses of unusual porphyrin systems and
their application as new materials. Porphyrins extended
by aromatic fragments function as highly modified
chromophores and therewith retain the properties inherent
to the porphyrin skeleton [1]. Highly conjugated por-
phyrins, e.g., benzoporphyrins and pyridinoporphyrins,
possess specific qualities usable in the field of medicine
or new materials for electronics [2, 3]. A new stage in
development of the chemistry of highly conjugated
porphyrins consisted in further modification of the
chromophore system of the porphyrin core by introducing
thereto more complicated aromatic and heteroaromatic
systems.At this stage alongside the traditional procedure
for expansion of the porphyrin macroring (building up of
an aromatic ring basing on a functionally substituted
porphyrin) a new more productive method was introduced
consisting in construction of a system of pyrrole and
aromatic fragment conjugated at the b-position of the
pyrrole ring with subsequent bringing of the system into
a porphyrin condensation [4–6]. The last approach
resulted in the synthesis of phenanthroporphyrins and
phenanthrolinoporphyrins, and also of thiadiazolo-
porphyrins which were taken up as molecular probes,
photosensitizers in the photodynamic therapy of cancer,
geochemical standards in the analysis of sedimentary
metalloporphyrins [6].
pyrrole containing various functional substituents in the
b-positions.
The present study concerns preparation of b-nitro-
and iodo-substituted pyrroles fit for further employment
in the [3+1] pyrrole condensation. We showed formerly
that direct pyrrole nitration was inefficient and frequently
led to the opening of the pyrrole ring. In the newly
developed synthesis we introduced the nitro group by
substituting halogen in the b-position by the nitro group
using silver nitrite. The reaction was performed by two
procedures: in one stage by treatment with silver nitrite
and iodine in acetonitrile, and in two stages involving first
introduction of a halogen followed by its replacement by
the nitro group.
The nitro group introduction by the first procedure
consisted in treating 2,5-dimethyl-4-ethoxycarbonyl-
pyrrole (I) in acetonitrile with a mixture of silver nitrite
and iodine; the yield of 2,5-dimethyl-3-nitro-4-ethoxy-
carbonylpyrrole (III) was 18%. Along the second way
we first prepared the b-halosubstituted pyrrole. The
iodination of 2,5-dimethyl-4-ethoxycarbonylpyrrole (I)
was carried out in aqueous methanol by the action of
iodine in the presence of KI and potassium carbonate,
and the yield of 3-iodo-2,5-dimethyl-4-ethoxycarbonyl-
pyrrole (II) reached 80%. The replacement of iodine for
nitro group was performed by boiling 3-iodo-2,5-dimethyl-
4-ethoxycarbonylpyrrole (II) with silver nitrite in
acetonitrile to get 2,5-dimethyl-3-nitro-4-ethoxycarbonyl-
pyrrole (III) in a 47% yield. Thus the second procedure
proved to be preferable for the overall yield along this
method was 37% against 18% by the one-stage process.
These systems were prepared by [3+1] synthesis
method [7]. This approach requires a preparation of
We planned to use the above method for preparation
of a b-halo-b-nitro-substituted pyrrole. To this end we
1070-4280/05/4111-1654Ó2005 Pleiades Publishing, Inc.

NEW IODO- AND NITRO-SUBSTITUTED PYRROLES
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synthesized b,b’-diiodopyrrole. This compound was
prepared in two stages. First 2,5-dimethyl-4-
ethoxycarbonylpyrrole (I) was subjected to hydrolysis by
boiling with 30% NaOH in methanol to obtain 2,5-di-
methyl-4-carboxypyrrole (IV) in a 65% yield; the iodina-
tion was performed in aqueous methanol by the action of
iodine in the presence of KI and potassium carbonate,
and the yield of 3,4-diiodo-2,5-di-methylpyrrole (V) was
45%. The substitution of iodine by nitro group was done
by the developed method of boiling 3,4-diiodo-2,5-
dimethyl-pyrrole (V) with silver nitrite in acetonitrile for
2 h or by keeping this mixture at room temperature for
24 h. However no substitution of iodine with nitro group
occurred. The main process consisted in oxidation of one
of the methyls into a formyl group. Apparently the silver
nitrite served as an oxidant. The oxidation product, 3,4-
diiodo-2-methyl-5-formylpyrrole (VI), was isolated as
a crystalline substance that fairly fast decomposed in air
thus preventing the measuring of the melting point. The
structure of compound VI was confirmed by spectral
methods. The IR spectrum contained a strong absorption
impact, 70 eV) and Kratos PC-Kompact MALDI 4
(evaporation with a lazer). The melting points were
measured on a Boetius heating block. Column chromato-
graphy was carried out on Silica gel 60 (Merck), the
solvents used were of “pure” and “extra pure” or Dried
grade. TLC was performed on Silufol UV-254 plates,
eluent hexane–ethyl acetate with different components
ratio. Development was carried out in iodine vapor, or by
heating to 120–140°C for 2–3 min, or under UV
irradiation.
..
3-Iodo-2,5-dimethyl-4-ethoxycarbonyl-pyrrole
(II). To a solution of 0.5 g (3 mmol) of 2,5-dimethyl-4-
ethoxycarbonylpyrrole (I) in 20 ml of methanol was added
dropwise at stirring a solution of 1.24 g (9 mmol) of K2CO3
in 20 ml of water, and the mixture was heated to 65°C.
At this temperature to the reaction mixture was added a
solution of 0.76 g (3 mmol) of I2 and 1.15 g (7 mmol) of
KI in 10 ml of water. The reaction mixture was stirred
for 20 min and then cooled. The precipitate was filtered
off and recrystallized from methanol. Yield 0.69 g (80%),
Rf 0.7 (hexane–ethyl acetate, 1:1), mp 116–120°C. IR
–1
–1
band of the C=O bond vibrations at 1670 cm . In the
spectrum,n, cm : 3256, 1675, 1217, 1099, 1029, 773.
1H NMR spectrum the singlet of the aldehyde proton
was observed at 9.35 ppm. The molecular ion in the mass
spectrum appeared at m/z 361.
1H NMR spectrum (CDCl3), d, ppm: 1.34 t (3H,
J 7.24 Hz), 2.22 s (3H), 2.47 s (3H), 4.26 q (2H,
J 7.24 Hz), 8.18 br.s (1H). 13C NMR spectrum (CDCl3),
d, ppm: 13.89 (2-CH3), 14.19 (3-CH3), 14.30
(OCH2CH3), 59.58 (C–I), 63.03 (CH2), 129.48 (C5),
129.55 (C4), 135.58 (C2), 164.62 (C=O). Mass spectrum,
m/z (Irel %): 293 (40), 279 (20), 264 (42), 248 (28), 219
(8), 127 (12),122 (25), 93 (30), 67 (35), 51 (55), 42 (100).
EXPERIMENTAL
IR spectra were recorded on a spectrophotometer
Shimadzu IR 435 from mulls in mineral oil. The 1H and
13C NMR spectra were registered on spectrometers
Bruker 200SY at operating frequencies 200 and 50 MHz
respectively and Bruker DPX-300 at operating
frequencies 300 and 75 MHz. Mass spectra were taken
on instruments Finnigan MAT INCOS 50 (electron
2,5-Dimethyl-3-nitro-4-ethoxycarbonyl-pyrrole
(III). To a solution of 0.4 g (1 mmol) of 3-iodo-2,5-
dimethyl-4-ethoxycarbonylpyrrole (II) in 5 ml of
acetonitrile was added 0.42 g (3 mmol) ofAgNO2 in 3 ml
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005

MIRONOV et al.
1656
of acetonitrile. The reaction mixture was boiled for 2 h
and left standing at room temperature in the dark for
2 days. The separated precipitate was filtered off , and
the product was subjected to column chromatography on
silica gel, eluent ethyl ether–petroleum ether, 1:2. Yield
0.1 g (47%), Rf 0.5 (hexane–ethyl acetate, 1:1), mp 110–
(6H), 8.01 br.s (1H). Mass spectrum, m/z (Irel %): 347
(100).
3,4-Diiodo-2-methyl-5-formylpyrrole (VI).
A mixture of 0.6 g (1.7 mmol) of 3,4-diiodo-2,5-
dimethylpyrrole (V), 7.5 ml of acetonitrile, and 0.63 g
(4 mmol) of silver nitrite was boiled for 2 h. The
acetonitrile was evaporated in a vacuum, the reaction
mixture was diluted with acetone and filtered from silver
salts. The reaction products were subjected to column
chromatography on silica gel, eluent petroleum ether–
ethyl acetate, 1:1. Yield 0.12 g (19%), Rf 0.64 (hexane–
–1
112°C. IR spectrum, n, cm : 3300, 1720, 1680, 1600.
1H NMR spectrum (CDCl3), d, ppm: 1.35 t (3H,
J 7.1 Hz), 2.35 s (3H), 2.48 s (3H), 4.32 q (2H, J 7.1 Hz),
8.91 br.s (1H). Mass spectrum, m/z (Irel %): 212 (19),
166 (40), 122 (43), 92 (45), 66 (28), 54 (19), 42 (100).
2,5-Dimethyl-4-carboxypyrrole (IV). A mixture
of 5 g (30 mmol) of 2,5-dimethyl-4-ethoxycarbonylpyrrole
(I), 36 ml of methanol, and 18 ml of 30% solution of
NaOH was boiled for 9 h, then cooled, and neutralized
with concn. HCl. The separated precipitate was filtered
off and dried in air. Yield 2.7 g (65%), Rf 0.8 (hexane–
ethyl acetate, 1:1), mp 180–184°C(decomp.). IR spectrum,
–1
ethyl acetate, 5:1). IR spectrum, n, cm : 3351, 1670.
1H NMR spectrum (CDCl3), d, ppm: 2.46 s (3H), 9.35 s
(1H), 10.13 br.s (1H). Mass spectrum, m/z (Irel %): 361
(100), 360 (60), 235 (21), 127 (47).
REFERENCES
–1
n, cm : 3260, 3000–2500, 1639. 1H NMR spectrum
1. Lash, T.D. and Novak B.H., Tetrahedron Lett., 1995, vol. 36,
p. 4381.
(D2O), d, ppm: 1.92 s (3H), 2.21 s (3H), 5.81 s (1H).
2. Lash, T.D., Chandrasekar, P., Osuma,A.T., Chaney, S.T., and
Spence, J.D., J. Org. Chem., 1998, vol. 63, p. 8455.
3. Vicente, M., Jaquinod, L., Khoury, R., Mandrona, A.,
Smith, K.M., Tetrahedron Lett., 1999, vol. 40, p. 8763.
4. Lin, Y. and Lash, T.D., Tetrahedron Lett., 1995, vol. 36,
p. 9441.
5. Novak, B.H. and Lash, T.D., J. Org. Chem., 1998, vol. 63,
p. 3998.
6. Lash, T.D., Wijesinghe, C., Osuma, A.T., and Patel, J.R.,
Tetrahedron Lett., 1997, vol. 38, p. 2031.
3,4-Diiodo-2,5-dimethylpyrrole (V). To a disper-
sion of 0.5 g (3.6 mmol) of 2,5-dimethyl-4-carboxypyrrole
(IV) in 20 ml of methanol was added dropwise at stirring
a solution of 1.24 g (9 mmol) of K2CO3 in 20 ml of water,
and the mixture was heated to 65°C. At this temperature
to the reaction mixture was added a solution of 0.76 g
(3 mmol) of I2 and 1.15 g (7 mmol) of KI in 10 ml of
water. The reaction mixture was stirred for 20 min and
then cooled. The precipitate was filtered off, washed with
water, and recrystallized from methanol. Yield 0.56 g
(45%), Rf 0.8 (hexane–ethyl acetate, 3:1), mp 116–120°C
(decomp.). 1H NMR spectrum (CDCl3), d, ppm: 2.28 s
7. Evtigneeva, R.P., Mironov,A.F., and Fleiderman, L.I., Dokl.
Akad. Nauk SSSR, 1973, vol. 210, p. 1090.
RUSSIAN JOURNALOF ORGANIC CHEMISTRY Vol. 41 No. 11 2005