New synthesis of pyrrole-2-carboxylic and pyrrole-2,5-dicarboxylic acid esters in the presence of iron-containing catalysts

Article abstract of DOI:10.1134/S1070428010070158

Alkyl 1H-pyrrole-2-carboxylates and dialkyl 1H-pyrrole-2,5-dicarboxylates were synthesized in quantitative yield by reactions of 1H-pyrrole, 2-acetyl-1H-pyrrole, and 1-methyl-1H-pyrrole with carbon tetrachloride and aliphatic alcohols in the presence of iron-containing catalysts. A probable reaction mechanism was proposed, and the rate constants and energies of activation of particular steps were determined on the basis of experimental data.

Full text of DOI:10.1134/S1070428010070158

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 7, pp. 1053–1059. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © R.I. Khusnutdinov, A.R. Baiguzina, R.R. Mukminov, I.V. Akhmetov, I.M. Gubaidullin, S.I. Spivak, U.M. Dzhemilev, 2010, published
in Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 7, pp. 1054–1060.
New Synthesis of Pyrrole-2-carboxylic
and Pyrrole-2,5-dicarboxylic Acid Esters in the Presence
of Iron-Containing Catalysts
R. I. Khusnutdinov, A. R. Baiguzina, R. R. Mukminov, I. V. Akhmetov, I. M. Gubaidullin,
S. I. Spivak, and U. M. Dzhemilev
Institute of Petroleum Chemistry and Catalysis, Russian Academy of Sciences,
pr. Oktyabrya 141, Ufa, 450075 Bashkortostan, Russia
e-mail: ink@anrb.ru
Received July 13, 2009
Abstract—Alkyl 1H-pyrrole-2-carboxylates and dialkyl 1H-pyrrole-2,5-dicarboxylates were synthesized in
quantitative yield by reactions of 1H-pyrrole, 2-acetyl-1H-pyrrole, and 1-methyl-1H-pyrrole with carbon
tetrachloride and aliphatic alcohols in the presence of iron-containing catalysts. A probable reaction mechanism
was proposed, and the rate constants and energies of activation of particular steps were determined on the basis
of experimental data.
DOI: 10.1134/S1070428010070158
Pyrrolecarboxylic acids attract strong interest as
starting compounds for the synthesis of porphyrins and
biologically active substances [1, 2]. For instance,
pyrrole-2-carboxylic acid derivatives exhibit antiviral
activity, in particular against classical bird influenza
viruses [3], whereas 5-arylpyrrole-2-carboxylic acid
sodium salts were found to possess anticonvulsant
activity [4].
in electrophilic substitution reactions; as a result,
a new substituent enters position 4 rather than free
position 5 [6, 7]. Only in the reaction with tert-butyl
hypochlorite, the desired 5-chloro-1H-pyrrole-2-car-
boxylic acid was obtained; this reaction is a very rare
example of radical replacement in the pyrrole ring [8].
The goal of the present work was to develop a gen-
eral procedure for the introduction of a carboxy group
into compounds of the pyrrole series via reaction with
the system CCl4–MeOH–catalyst. We showed previ-
ously [9] that such reaction is successful with thio-
phene and its derivatives [9]. As model substrate we
used 2-acetyl-1H-pyrrole. We found that the reaction
of 2-acetyl-1H-pyrrole with carbon tetrachloride and
methanol in the presence of a catalyst is regioselective
and that the only product is methyl 5-acetyl-1H-pyr-
role-2-carboxylic acid (Ia). As catalysts we used Ni,
Cu, Mn, Pd, V, and Fe compounds and complexes
which are known to activate C–Cl bond in CCl4 mole-
cule [9, 10]. The highest catalytic activity was ob-
served for the following iron compounds: Fe(OAc)2,
Fe(C5H5)2, FeBr2, and Fe(acac)3. The optimal condi-
tions were temperature 115°C and reaction time 6 h; in
this case the conversion of initial 2-acetyl-1H-pyrrole
was complete, and the yield of ester Ia reached 98%
(Scheme 1).
A specific feature of pyrrolecarboxylic acids is that
the carboxy group therein, regardless of its position,
can readily be replaced by other functional groups. Re-
placement of carboxy group by the action of electro-
philic reagents occurs more readily than replacement
of hydrogen [5, 6]. For example, nitration of pyrrole-
carboxylic acids with nitric acid in acetic anhydride
gives mixtures of nitropyrrolecarboxylic acids and
2-nitropyrrole. The carboxy group in pyrrole-2-carbox-
ylic acid is replaced most smoothly by halogen atoms.
Published data on the synthesis of pyrrolecarbox-
ylic acids, in particular of an important representative
of this series of compounds, 5-acetyl-1H-pyrrole-2-
carboxylic acid, are very few in number. Difficulties in
the synthesis of this acid are related to the effect of
a strong electron-withdrawing substituent (COOH,
COOCH3, COCH3) in position 2 of the pyrrole ring,
which changes the regioselectivity intrinsic to pyrrole
1053

KHUSNUTDINOV et al.
Special experiments showed that the examined
1054
Scheme 1.
reaction can be performed successfully with other
tetrahalomethanes such as CBr4 and BrCCl3 and that
chloroform, bromoform, and methylene chloride failed
to react. The reactions with CBr4 and BrCCl3 require
lower temperature (105°C) and are complete in 3 h.
Me
+ CCl4 + MeOH
N
H
O
Catalyst
115°C, 6 h
Me
OMe
N
–HCl
The following reaction mechanism seems to be the
most probable. Taking into account aromaticity of
2-acetyl-1H-pyrrole and the presence of a Lewis acid
(FeBr2), the formation of compound Ia via alkylation
with carbon tetrachloride, followed by methanolysis of
trichloromethyl derivative II, is possible (Scheme 2).
Although our attempts to detect intermediate com-
pound II in the reaction mixture were unsuccessful, its
participation provides the best rationalization for the
formation of methyl 5-acetyl-1H-pyrrole-2-carboxylate
(Ia). The proposed mechanism is detailed in Scheme 3.
H
O
O
Ia
Catalyst
Yield of Ia, %
Fe(C5H5)2
Fe(acac)3
Fe(OAc)2
FeBr2
98
95
90
87
The classical procedure for the preparation of com-
pound Ia by acylation of methyl 1H-pyrrole-2-car-
boxylate with acetic anhydride is not selective: as
a result, a mixture of ester Ia and isomeric methyl
4-acetyl-1H-pyrrole-2-carboxylate is formed. Further-
more, the latter is obtained as the major product (yield
73%) in the presence of AlCl3 as catalyst, while the
yield of Ia does not exceed 8% [11]. The reaction in
the presence of HClO4 gives an equimolar mixture of
ester Ia and methyl 4-acetyl-1H-pyrrole-2-carboxylate
[12]. Ethyl 5-acetyl-1H-pyrrole-2-carboxylate was
synthesized in 37% yield by reaction of ethyl 1H-pyr-
role-2-carboxylate with acetyl chloride in the presence
of ZnCl2 [13].
Scheme 2.
Me
Me
[Fe]
+ CCl4
CCl3
N
N
–HCl
H
H
O
O
II
OMe
Me
MeOH
–HCl, –Me2O
N
H
O
O
Ia
We also derived a kinetic model for the formation
of methyl 5-acetyl-1H-pyrrole-2-carboxylate (Ia). The
kinetic model includes mathematical description as
nonlinear differential equations for concentrations of
compounds involved in the process. The laboratory
reactor was simulated by the ideal mixing model [14],
for which the material balance equations are given by
the system
The structure of compound Ia was determined by
1H and 13C NMR spectroscopy, including two-dimen-
sional correlation techniques (HSQC, HMBC). Signals
from directly coupled protons and carbon atoms in the
acetyl and methoxycarbonyl groups, as well as from
the endocyclic CH groups (δC 116.04, δ 6.84 ppm;
δC 115.58, δ 6.89 ppm), were unambiguously assigned
on the basis of H–13C heteronuclear correlation ex-
1
m
∂xi F − xi FN
i
periments (HSQC). The substitution pattern in the pyr-
role ring was reliably determined by analysis of the
HMBC heteronuclear correlation spectra. The most in-
formative was the signal from protons in the acetyl
group at δ 2.48 ppm which displayed geminal coupling
with the carbonyl carbon atom (C8) and vicinal cou-
pling with the C5 atom in the pyrrole ring. The C5
nucleus (δC 134.20 ppm) showed in turn a cross peak
with 4-H (δ 6.84 ppm). A considerably weaker correla-
tion between 4-H and C2 (δC 126.93 ppm) corresponds
to long-range vicinal heteronuclear interaction, which
confirms the position of the CO2CH3 and COCH3
groups at C2 and C5 of the pyrrole ring.
F = ν w
=
;
(1)
∑
i
ij
j
∂t
N
j=1
with the following entry conditions: at t = 0: xi = xio,
N = 1; here, N = c/c0 is the relative change in the
number of moles in the reaction mixture; c and c0 are
the molar density and its initial value; xi are the con-
centrations of the components (mole fractions); i = 1
(2-acetyl-1H-pyrrole), i = 2 (CCl4), i = 3 (2-acetyl-5-
trichloromethyl-1H-pyrrole), i = 4 (HCl), i = 5
(MeOH), i = 6 [2-acetyl-5-dichloro(methoxy)methyl-
1H-pyrrole], i = 7 [2-acetyl-5-chloro(dimethoxy)meth-
yl-1H-pyrrole], i = 8 (2-acetyl-5-trimethoxymethyl-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

NEW SYNTHESIS OF PYRROLE-2-CARBOXYLIC AND PYRROLE-2,5-DICARBOXYLIC
1055
Scheme 3.
Me
Me
+ CCl4
+ HCl
CCl3
N
N
H
H
O
O
II
E1 = 96.7 kJ/mol; k1 = 0.044 (105°C), 0.052 (110°C), 0.1 h–1 (115°C).
Me
Me
OMe
Cl
+ MeOH
+ HCl
CCl3
N
N
H
H
O
O
Cl
E2 = 7.96 kJ/mol; k2 = 0.015 (105°C), 0.016 (110°C), 0.017 h–1 (115°C).
Me
OMe
Cl
Me
OMe
OMe
+ MeOH
+ HCl
N
N
H
H
O
O
Cl
Cl
E3 = 7.58 kJ/mol; k3 = 0.013 (105°C), 0.014 (110°C), 0.015 h–1 (115°C).
Me
OMe
OMe
Me
OMe
OMe
+ MeOH
+ HCl
N
N
H
H
O
O
MeO
Cl
E4 = 7.75 kJ/mol; k4 = 0.0013 (105°C), 0.0014 (110°C), 0.0015 h–1 (115°C).
Me
OMe
OMe
Me
OMe
+ Me2O
N
N
H
H
O
MeO
O
O
Ia
E5 = 7.67 kJ/mol; k5 = 1.756 (105°C), 1.812 (110°C), 1.87 h–1 (115°C).
1H-pyrrole), i = 9 [methyl 5-acetyl-1H-pyrrole-2-car-
boxylate (Ia)], i = 10 (dimethyl ether).
experimental data. The kinetic constants were estimat-
ed by random search followed by parabolic descend at
a selected direction with an accuracy of 10–3 [17]. As
a result, we found several sets of constants which
equally conformed to the experimental data. To
remove ambiguity in the determination of the rate con-
stants, experimental data obtained at different tempera-
tures were treated. Correction of the rate constants at
different temperatures with the aid of the Arrhenius
equation allowed us to define a single set of constants
describing the entire experimental temperature range.
The constants ki (h–1) are some reduced quantities with
a dimension of reciprocal time, which are related to the
true constants Ki (l mol–1 h–1) by the equations ki =
Ki c0 (i = 1−4), k5 = K5. In keeping with the proposed
kinetic model, the rate-determining step is alkylation
of 2-acetyl-1H-pyrrole with carbon tetrachloride.
The right parts of system (1) look as follows:
F1 = –w1; F2 = –w1; F3 = w1 – w2; F4 = w1 + w2 + w3 + w4;
F5 = w2 – w3 – w4 ; F6 = w2 – w3; F7 = w3 – w4; F8 = w4 – w5;
F9 = w5; F10 = w5; F11 = FN = w5.
The developed model appropriately describes the
experimental findings: deviations between the calculat-
ed and experimental variations in the reactant concen-
trations do not exceed 7%. In this work we used
an informational analytical system of inverse problems
of chemical kinetics [15]. With the aid of mathematical
model (1) we solved the reverse kinetic problem and
determined the kinetic parameters (rate constants and
energies of activation of particular steps). There is no
universal method for the solution of inverse problem
[16]. In any way, it is solved by searching over a series
of primal problems according to a specified program to
minimize the deviation between the calculated and
Figures 1 and 2 compare the experimental (dark
circles, squares, and triangles) and calculated data
(continuous lines) on variation of the component con-
centrations x1 and x9 during the process. Excellent
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KHUSNUTDINOV et al.
methyl-1H-pyrrole (II)] were detected in the reaction
1056
1.0
mixture at any moment of time. On the other hand, the
formation of 2-acetyl-5-trichloromethyl-1H-pyrrole
(II) as intermediate is indirectly supported by the fact
that replacement of methanol by ethyl, propyl, and
isopropyl alcohols resulted in the formation of ethyl,
propyl, and isopropyl 5-acetyl-1H-pyrrole-2-carbox-
ylates Ib–Id, respectively, in fairly good yields
(Scheme 4). In addition, hydrogen chloride and di-
methyl ether were detected in the reaction mixture.
0.8
0.6
0.4
0.2
0.0
1
2
3
0
1
2
3
4
5
6
7
Time, h
According to the experimental data, the optimal
reactant ratio iron-containing catalyst–2-acetyl-1H-
pyrrole–CCl4–ROH is 1 : 100 :750 :6500. We made
an attempt to involve unsubstituted pyrrole and
N-methylpyrrole in analogous reaction with CCl4 and
CH3OH under the optimal conditions. Freshly distilled
pyrrole reacted quite readily to produce dimethyl
1H-pyrrole-2,5-dicarboxylate (IIIa) in quantitative
yield (Scheme 5). The reaction with pyrrole may be
catalyzed by the following iron compounds: Fe(acac)3,
Fe(OAc)2, and FeBr2. Ferrocene showed no catalytic
activity.
Fig. 1. Calculated and experimental data for the consumption
of 2-acetyl-1H-pyrrole at (1) 105, (2) 110, and (3) 115°C.
1.0
0.8
0.6
0.4
0.2
0.0
3
2
1
Analogous reaction with N-methylpyrrole gave rise
to a mixture of methyl 1-methyl-1H-pyrrole-2-carbox-
ylate (IVa) and dimethyl 1-methyl-1H-pyrrole-2,5-
dicarboxylate (IVb). In this case, the effect of the
catalyst nature was especially strong. The reaction in
the presence of FeBr2 afforded dimethyl 1-methyl-1H-
pyrrole-2,5-dicarboxylate (IVb) with high selectivity,
whereas methyl 1-methyl-1H-pyrrole-2-carboxylate
(IVa) was formed as the major product in the reaction
catalyzed by ferrocene (Scheme 6). When the reaction
was carried out at lower temperature (~85–105°C),
a more complex mixture was obtained due to forma-
tion of condensation products at the free 5-position of
the pyrrole ring [18].
0
1
2
3
4
5
6
7
Time, h
Fig. 2. Calculated and experimental data for the formation
of methyl 5-acetyl-1H-pyrrole-2-carboxylate (Ia) at (1) 105,
(2) 110, and (3) 115°C.
agreement is observed between the calculated and
experimental data at any temperature: 105, 110, and
115°C. The energies of activation of the elementary
steps decrease in the following order: E1 = 96.7 > E2 =
7.96 > E4 = 7.75 > E5 = 7.67 > E3 = 7.58 kJ/mol. The
energy of activation of the first elementary step
exceeds those of the other steps by more than order of
magnitude. Presumably, this is the reason why no in-
termediate products [in particular, 2-acetyl-5-trichloro-
To conclude, we have developed a general proce-
dure for the introduction of a carboxy group into the
Scheme 4.
Me
Me
Me
OMe
Fe(C5H5)2
–HCl
MeOH
+ CCl4
CCl3
N
N
N
–3 HCl, –Me2O
H
H
H
O
O
O
O
II
Ia
Fe(C5H5)2
115°C, 6 h
Me
O
Me
OR
+ CCl4 + ROH
N
N
H
H
O
O
Ia–Id
R = Me (a, yield 98%), Et (b, 97%), Pr (c, 81%), i-Pr (d, 62%).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

NEW SYNTHESIS OF PYRROLE-2-CARBOXYLIC AND PYRROLE-2,5-DICARBOXYLIC
1057
Scheme 5.
Catalyst
110°C, 6 h
MeO
OMe
+ CCl4 + MeOH
N
N
H
–HCl
H
O
O
IIIa
Catalyst = Fe(acac)3 (yield of IIIa 99%), Fe(OAc)2 (97%), FeBr2 (95%).
Scheme 6.
OMe
MeO
OMe
Fe(C5H5)2, 110°C, 3 h
Conversion 100%
+
N
N
O
O
O
Me
Me
IVa
10:1
IVb
+ CCl4 + MeOH
N
Me
MeO
OMe
FeBr2, 110°C, 8 h
Conversion 100%
N
O
O
Me
IVb, 95%
pyrrole ring using unsubstituted pyrrole, 2-acetyl-1H-
pyrrole, and 1-methyl-1H-pyrrole as examples. Prob-
able reaction mechanism was studied with the aid of
mathematical simulation.
(0.45 mmol) of 2-acetyl-1H-pyrrole, 0.34 ml
(3.5 mmol) of carbon tetrachloride, and 29 mmol of
the corresponding alcohol (1.2 ml of methanol, 1.7 ml
of ethanol, 2.2 ml of propan-1-ol, or 2.2 ml of propan-
2-ol). The ampule was sealed and placed into a high-
pressure reactor which was hermetically capped and
heated for 6 h at 115°C under continuous stirring.
When the reaction was complete, the reactor was
cooled to 20°C, the ampule was opened, the reaction
mixture was filtered through a layer of silica gel (2 g),
the sorbent was washed with hexane–diethyl ether
(1:1), the solvent was distilled off, and the residue was
recrystallized from benzene–hexane.
EXPERIMENTAL
1
The H and 13C NMR spectra were recorded on
Bruker Avance-400 (400.13 and 100.62 MHz, respec-
tively) and Jeol FX-90Q (90 and 22.5 MHz, respec-
tively) spectrometers using CDCl3 as solvent; the
chemical shifts are given relative to tetramethylsilane.
The mass spectra (electron impact, 70 eV) were ob-
tained on a Finnigan MAT-112S GC–MS system.
Chromatographic analysis was performed on
a Shimadzu GC-9A instrument (2-m×3-mm column
packed with 5% of SE-30 on Chromaton N-AW-
HMDS; oven temperature programming from 50 to
270°C at a rate of 8 deg/min; carrier gas helium, flow
rate 47 ml/min).
Methyl 5-acetyl-1H-pyrrole-2-carboxylate (Ia).
Yield 98%, mp 112.5°C; published data: mp 109–
1
110 [11], 110–111.5°C [12]. H NMR spectrum, δ,
ppm: 2.48 s (3H, CH3CO), 3.90 s (3H, OCH3), 6.80–
13
6.95 m (2H, 3-H, 4-H), 9.89 br.s (1H, NH). C NMR
spectrum, δC, ppm: 25.85 (COCH3), 52.04 (OCH3),
115.58 (C3), 116.04 (C4), 134.18 (C2), 155.50 (C5),
161.50 (COOCH3), 188.59 (COCH3). Mass spectrum,
m/z (Irel, %): 167 (96) [M]+, 43 (25), 53 (15), 64
(12), 92 (24), 118 (20), 120 (100), 136 (45), 152 (80),
153 (100).
Commercially available 2-acetyl-1H-pyrrole, pyr-
role, N-methylpyrrole, methanol, ethanol, propan-1-ol,
propan-2-ol, and carbon tetrachloride were distilled
prior to use. Tris(acetylacetonato)iron(III), iron(II)
acetate, ferrocene, and iron(II) bromide (from Acros)
were recrystallized and dried in a vacuum desiccator
prior to use. The reactions were carried out under
continuous stirring in a glass 10-ml ampule which was
placed into a 17-ml stainless steel high-pressure
reactor maintained at a required temperature.
Ethyl 5-acetyl-1H-pyrrole-2-carboxylate (Ib).
Yield 98%, mp 59–60°C; published data: mp 54–57
1
[13], 60–60.5°C [19]. H NMR spectrum, δ, ppm:
1.38 t (3H, CH3CH2, J = 6.8 Hz), 2.48 s (3H, COCH3),
4.36 q (2H, OCH2, J = 7.2 Hz), 6.75–6.95 m (2H, 3-H,
4-H), 9.81 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
14.32 (CH2CH3), 25.85 (COCH3), 61.15 (OCH2),
115.48 (C3), 116.05 (C4), 134.18 (C2), 155.52 (C5),
161.68 (COO), 188.65 (COCH3).
Alkyl 5-acetyl-1H-pyrrole-2-carboxylates Ia–Id
(general procedure). An ampule was charged under
argon with 0.001 g (0.0045 mmol) of Fe(C5H5)2, 0.05 g
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KHUSNUTDINOV et al.
1058
13
Propyl 5-acetyl-1H-pyrrole-2-carboxylate (Ic).
(3H, OCH3), 6.10–7.10 m (2H, 3-H, 4-H). C NMR
spectrum, δC, ppm: 36.26 (NCH3), 50.46 (OCH3),
107.58 (C4), 117.56 (C3), 129.31 (C2), 127.54 (C5),
161.26 (C=O). Mass spectrum, m/z (Irel, %): 139
(60) [M]+, 45 (15), 53 (28), 80 (25), 94 (15), 108 (100),
124 (4).
1
Yield 81%, mp 42–44°C. H NMR spectrum, δ, ppm:
3
1.02 t (3H, CH3CH2, J = 7.2 Hz), 1.7–1.9 m (2H,
CH3CH2), 2.42 s (3H, CH3CO), 4.26 t (2H, OCH2, 3J =
6.8 Hz), 6.80–7.28 m (2H, 3-H, 4-H), 9.89 br.s (1H,
NH). 13C NMR spectrum, δC, ppm: 9.76 (CH3CH2),
21.48 (CH3CH2), 25.68 (COCH3), 66.55 (OCH2),
115.44 (C3), 116.07 (C4), 127.34 (C2), 146.19 (C5),
160.46 (COO), 188.61 (COCH3).
Dimethyl 1-methyl-1H-pyrrole-2,5-dicarboxylate
(IVb). Yield 95%, mp 78–80°C; published data [22]:
mp 80–80.5°C. 1H NMR spectrum, δ, ppm: 4.16 s (3H,
NCH3), 3.75 s (6H, OCH3), 6.8 s (2H, 3-H, 4-H).
13C NMR spectrum, δC, ppm: 34.12 (NCH3), 51.18
(OCH3), 116.07 (C3, C4), 127.63 (C2, C5), 161.07
(C=O). Mass spectrum, m/z (Irel, %): 197 (72) [M]+, 45
(18), 69 (10), 79 (10), 97 (8), 108 (10), 120 (14), 138
(8), 152 (15), 166 (100), 182 (5).
Isopropyl 5-acetyl-1H-pyrrole-2-carboxylate
(Id). Yield 62%, mp 67°C. 1H NMR spectrum, δ, ppm:
3
1.36 d [6H, (CH3)2CH, J = 6 Hz], 2.42 s (3H,
CH3CO), 4.95–5.5 m (1H, OCH), 6.80–7.72 m (2H,
3-H, 4-H), 9.83 br.s (1H, NH). 13C NMR spectrum, δC,
ppm: 21.92 [(CH3)2CH], 25.84 (COCH3), 68.86
(OCH), 115.39 (C3), 116.09 (C4), 124.56 (C2), 134.53
(C5), 159.92 (COO), 188.65 (COCH3).
Dimethyl 1H-pyrrole-2,5-dicarboxylate (IIIa).
An ampule was charged under argon with 0.0016 g
(0.0045 mmol) of Fe(acac)3, 0.03 g (0.45 mmol) of
pyrrole, 0.54 g (3.5 mmol) of CCl4, and 0.94 g
(29 mmol) of MeOH. The reaction was carried out,
and the reaction mixture was treated, as described
above for compounds Ia–Id. Yield 99%, mp 129–
130°C; published data [20]: mp 132°C. 1H NMR spec-
trum, δ, ppm: 3.93 s (6H, OCH3), 6.89 s (2H, 3-H,
4-H), 9.64 br.s (1H, NH). 13C NMR spectrum, δC, ppm:
34.12 (NCH3), 51.96 (OCH3), 115.56 (C3, C4), 119.69
(C2, C5), 162.00 (COO).
Kinetic study on the formation of methyl
5-acetyl-1H-pyrrole-2-carboxylate (Ia). A series of
experiments on the synthesis of compound (Ia) from
2-acetyl-1H-pyrrole were performed according to the
above described procedure with variation of the reac-
tion time (2.5, 3, 3.5, 4, 4.5, 5, 6 h) and temperature
(105, 110, 115°C). The conversion of initial 2-acetyl-
1H-pyrrole and the yield of methyl 5-acetyl-1H-pyr-
role-2-carboxylate (Ia) were determined by GLC using
decane as internal standard.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 09-03-00472) and by the Ministry of Education
and Science of the Russian Federation (project
no. NSh 2349.2008.3).
Methyl 1-methyl-1H-pyrrole-2-carboxylate (IVa)
and dimethyl 1-methyl-1H-pyrrole-2,5-dicarbox-
ylate (IVb). An ampule was charged under argon with
0.001 g (0.0045 mmol) of Fe(acac)2 (in the synthesis
of IVa) or 0.001 g (0.0045 mmol) of FeBr2 (in the syn-
thesis of IVb), 0.036 g (0.45 mmol) of N-methylpyr-
role, 0.54 g (3.5 mmol) CCl4, and 0.94 g (29 mmol) of
MeOH. The ampule was sealed and placed into a high-
pressure reactor, and the reactor was hermetically
closed and heated at 110°C for 3 (IVa) or 8 h (IVb)
under continuous stirring. When the reaction was
complete, the reactor was cooled to 20°C, the ampule
was opened, the reaction mixture was filtered through
a layer of silica gel (2 g), the sorbent was washed with
hexane–diethyl ether (1:1), and the solvent was dis-
tilled off. Compound IVa was distilled under reduced
pressure, while compound IVb was recrystallized from
benzene–hexane (1:1).
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