Reaction of α-nitrocinnamic acid esters with pyrrole

Full text of DOI:10.1134/S1070428008060262

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 6, pp. 931–932. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © L.V. Baichurina, R.I. Baichurin, N.I. Aboskalova, G.A. Berkova, V.M. Berestovitskaya, 2008, published in Zhurnal Organicheskoi
Khimii, 2008, Vol. 44, No. 6, pp. 937–938.
SHORT
COMMUNICATIONS
Reaction of α-Nitrocinnamic Acid Esters with Pyrrole
L. V. Baichurina, R. I. Baichurin, N. I. Aboskalova, G. A. Berkova, and V. M. Berestovitskaya
Hertzen Russian State Pedagogical University, nab. r. Moiki 48, St. Petersburg, 191186 Russia
e-mail: kohrgpu@yandex.ru
Received February 15, 2008
DOI: 10.1134/S1070428008060262
Synthetically accessible α-nitrocinnamic acid esters
may be regarded as promising precursors of β-phenyl-
alanine and its substituted derivatives [1–4]. Undoubt-
edly, introduction into their molecules of pharmaco-
phoric structural fragments, e.g., pyrrole ring, attracts
interest. Pyrrole ring constitutes the key fragment of
porphyrin macroring which is the base of a number of
important natural compounds, such as hemoglobin,
chlorophyll, and cytochrome. Some medical agents,
e.g., Ketorolac (analgesic and antiinflammatory drug),
Atorvastatin (cholesterol-lowering agent) [5, 6], etc.,
contain a pyrrole ring in their molecules.
pounds IIa and IIc displayed absorption at 3450–
3465 cm–1 due to stretching vibrations of the pyrrole
N–H group.
1
In the H NMR spectrum of compound IIa we
observed two well-resolved doublets at δ 5.76 and
5.06 ppm, which belong to the HA and HB protons
(3JAB = 11.03 Hz); protons of the ethoxy group reso-
nated as a triplet and quartet at δ 0.88 and 3.96 ppm,
respectively. Signals in the regions δ 7.20–7.40 and
6.10–6.63 ppm were assigned to protons in the ben-
zene and pyrrole rings, and the NH proton gave
a downfield signal at δ 8.61 ppm. The 1H NMR spectra
of esters IIb and IIc contained doubled sets of signals,
indicating the presence of two diastereoisomers.
Initial ethyl α-nitrocinnamates Ia and Ib were
synthesized by reactions of ethyl nitroacetate [7] with
the corresponding Schiff bases or diacetals according
to the procedures described in [8–10] or by direct acid-
catalyzed alkenylation of ethyl nitroacetate with aro-
matic aldehydes according to the procedure proposed
previously for the preparation of geminal acylnitro-
ethenes [11–13].
We were the first to react α-nitrocinnamic acid
esters Ia and Ib with pyrrole and N-methylpyrrole. The
reactions were carried out with excess pyrrole reagent
at room temperature under solvent-free conditions in
the absence of catalyst, and the yields of the corre-
sponding addition products were 48–52%. Ethyl
3-aryl-2-nitro-3-(1H-pyrrol-2-yl)propanoates IIa–IIc
were isolated as slightly colored crystalline substances.
Compound IIa was isolated as a single diastereo-
isomer, while esters IIb and IIc were mixtures of
erythro and threo isomers.
Ethyl 2-nitro-3-phenyl-3-(1H-pyrrol-2-yl)propa-
noate (IIa). Pyrrole, 0.67 g (10 mmol), was added to
0.22 g (1 mmol) of ethyl 2-nitro-3-phenylprop-2-
enoate (Ia), and the mixture was left to stand at room
temperature in the dark. After 48 h, ethyl acetate and
water (4:1) were added to the mixture, the aqueous
The structure of the products was confirmed by
spectral data. The IR spectra of IIa–IIc contained
strong absorption bands due to stretching vibrations of
nonconjugated nitro (1565–1570, 1370–1375 cm–1)
and carbonyl groups (1750 cm–1); in addition, com-
N
R'
HA
NO2
COOEt
HB
COOEt
+
N
NO2
R
R
R'
Ia, Ib
IIa–IIc
I, R = H (a), MeO (b); II, R = R′ = H (a), R = H, R′ = Me (b), R = MeO, R′ = H (c).
931

BAICHURINA et al.
932
phase was separated in a separatory funnel, the organic
phase was washed with two portions of a saturated
solution of sodium chloride and dried over calcined
magnesium sulfate, the solvent was evaporated in air,
and the residue was treated with ethanol. Yield 0.139 g
(48%), off-white crystals, mp 128–130°C (from
EtOH). IR spectrum, ν, cm–1: 1570, 1370 (NO2); 1750
The IR spectra were recorded on a InfraLYuM FT-
02 spectrometer with Fourier transform using CHCl3
as solvent (concentration 40 mg/ml). The H NMR
spectra were measured on a Bruker WM-400 spec-
trometer from solutions in chloroform-d using hexa-
methyldisiloxane as internal reference.
1
1
(C=O); 3450 (NH). H NMR spectrum, δ, ppm: 0.88 t
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3
(3H, CH3); 3.96 q (2H, OCH23); 5.76 d (1H, HA, JAB
=
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11.03 Hz); 5.06 d (1H, HB, JAB = 11.03 Hz); 6.10,
6.12, and 6.63 (3H, pyrrole); 7.20–7.40 m (5H, Harom);
8.61 s (1H, NH). Found, %: N 9.92. C15H16N2O4. Cal-
culated, %: N 9.72.
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Compounds IIb and IIc were synthesized in a simi-
lar way; in the synthesis of IIc, the mixture was kept
for 72 h.
Ethyl 3-(1-methyl-1H-pyrrol-2-yl)-2-nitro-3-
phenylpropanoate (IIb). Yield 51%, colorless crys-
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1
cm–1: 1565, 1375 (NO2); 1750 (C=O). H NMR spec-
trum, δ, ppm: 6.04, 6.17, and 6.51 (3H, pyrrole); 7.20–
7.30 m (5H, Harom); diastereoisomer A: 0.89 t (CH3),
3
3.39 s (NCH3), 3.87 q (OCH2), 5.64 d (HA, JAB
=
3
11.77 Hz), 5.03 d (HB, JAB = 11.77 Hz); diastereoiso-
mer B: 1.15 t (CH3), 3.44 s (NCH3), 4.16 q (OCH2),
3
3
5.67 d (HA, JAB = 11.03 Hz), 4.97 d (HB, JAB
=
7. Radionov, V.M., Machinskaya, I.V., and Belikov, V.M.,
11.03 Hz); ratio A : B = 1 : 2. Found, %: N 9.53.
C16H18N2O4. Calculated, %: N 9.27.
Sintez Org. Soedin., 1950, vol. 1, p. 117.
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Garbalinskaya, M.S., and Bakhmutov, V.I., Izv. Akad.
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Ethyl 3-(4-methoxyphenyl)-2-nitro-3-(1H-pyr-
rol-2-yl)propanoate (IIc). Yield 52%, colorless crys-
tals, mp 106–108°C (from hexane). IR spectrum, ν,
cm–1: 1565, 1375 (NO2); 1750 (C=O); 3465 (NH).
1H NMR spectrum, δ, ppm: 5.99, 6.10, and 6.68 (3H,
pyrrole); 6.80–7.30 m (4H, Harom); diastereoisomer A:
1.00 t (CH3), 3.77 s (OCH3), 3.99 q (OCH2), 5.70 d
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3
3
(HA, JAB = 10.90 Hz), 5.05 d (HB, JAB = 10.90 Hz),
8.42 s (NH); diastereoisomer B: 1.18 t (CH3), 3.77 s
3
(OCH3), 4.19 q (OCH2), 5.67 d (HA, JAB = 11.03 Hz),
5.04 d (HB, 3JAB = 11.03 Hz), 8.52 s (NH); ratio A:B =
1:2. Found, %: N 8.84. C16H18N2O5. Calculated, %:
N 8.81.
Zh. Org. Khim., 1980, vol. 16, p. 2157.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 44 No. 6 2008