Expedient Strategy for the Synthesis of 5-Acylethynylpyrrole-2-carbaldehydes

Article abstract of DOI:10.1080/00397911.2015.1034873

5-Acylethynylpyrrole-2-carbaldehydes have been synthesized from the protected pyrrole-2-carbaldehydes by their transition-metal-free topochemical mechanoactivated ethynylation with acylbromoacetylenes in a solid Al₂O₃ medium (room te

Full text of DOI:10.1080/00397911.2015.1034873

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Expedient Strategy for the Synthesis of
5-Acylethynylpyrrole-2-carbaldehydes
Denis N. Tomilina, Lyubov N. Sobeninaa, Marina V. Markovaa, Maxim
D. Gotskoa, Igor A. Ushakova, Vladimir I. Smirnova, Alexander V.
Vaschenkoa, Albina I. Mikhalevaa & Boris A. Trofimova
a A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences, Irkutsk, Russian Federation
Accepted author version posted online: 02 Apr 2015.Published
online: 02 Apr 2015.
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To cite this article: Denis N. Tomilin, Lyubov N. Sobenina, Marina V. Markova, Maxim D. Gotsko, Igor
A. Ushakov, Vladimir I. Smirnov, Alexander V. Vaschenko, Albina I. Mikhaleva & Boris A. Trofimov
(2015): Expedient Strategy for the Synthesis of 5-Acylethynylpyrrole-2-carbaldehydes, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
DOI: 10.1080/00397911.2015.1034873
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Synthetic Communications1, 0: 1–10, 2015
Copyright © Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397911.2015.1034873
EXPEDIENT STRATEGY FOR THE SYNTHESIS OF
5-ACYLETHYNYLPYRROLE-2-CARBALDEHYDES
Denis N. Tomilin, Lyubov N. Sobenina, Marina V. Markova,
Maxim D. Gotsko, Igor A. Ushakov, Vladimir I. Smirnov,
Alexander V. Vaschenko, Albina I. Mikhaleva, and
Boris A. Trofimov
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian
Academy of Sciences, Irkutsk, Russian Federation
GRAPHICAL ABSTRACT
Abstract 5-Acylethynylpyrrole-2-carbaldehydes have been synthesized from the protected
pyrrole-2-carbaldehydes by their transition-metal-free topochemical mechanoactivated
ethynylation with acylbromoacetylenes in a solid Al2O3 medium (room temperature, 6 h,
41–54% yields).
Keywords Acylbromoacetylenes; Al2O3; ethynylation; 5-ethynylpyrrole-2-carbaldehydes;
pyrrole-2-carbaldehydes
INTRODUCTION
The pyrrole ring is a key structural motif of many biologically important
natural compounds such as chlorophyll, hemoglobin, vitamin B12, alkaloids, and
antibiotics involved in the bioconversion of solar energy, oxygen transfer processes,
Received February 24, 2015.
Address correspondence to Boris A. Trofimov, A. E. Favorsky Irkutsk Institute of Chemistry,
Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation.
E-mail: boris_trofimov@irioch.irk.ru
Color versions of one or more of the figures in the article can be found online at www.tandfonline.
com/lsyc.
1

2
D. N. TOMILIN ET AL.
and other life-supporting reactions.[1] Among representatives of the pyrrole series,
ethynyl derivatives occupy an important place. Because of the presence of such
highly reactive counterparts as the pyrrole ring and the carbon-carbon triple bond
in one molecule, these compounds can be divergently used for the synthesis of vari-
ous functionalized heterocyclic systems as well as conjugated and fused pyrrolic
ensembles.[2] Ethynylpyrroles additionally functionalized with the aldehyde group
are of even greater biological and synthetic interest. The ethynylpyrrolecarbalde-
hydes have been employed as precursors for the synthesis of polyfunctional deriva-
tives of pyrrole and indole.[3] They are also used in a design of macrocycles, closely
related to natural ones, which possess important biological properties.[4]
In this regard, the search for efficient and facile approaches to preparation of
ethynylpyrrolecarbaldehydes represents a timely synthetic task.
Currently, ethynylpyrrolecarbaldehydes are obtained by cross-coupling of hardly
available and unstable halopyrrolecarbaldehydes with terminal acetylenes[3d–f,4]
(Sonogashira reaction) or their organometallic derivatives[5] in the presence of
palladium catalysts. However, the ethynylpyrrolecarbaldehydes containing electron-
acceptor functions in the acetylene substituent remain almost unknown. This approach
for electron-deficient functionalized acetylenes was stated to be of poor efficiency.[6]
Meanwhile, ethynylpyrrolecarbaldehydes with electron-withdrawing functions in
acetylene substitutents are desirable building blocks for the preparation of poly-
functional stable organic radicals and polyradicals, which attract intense interest as
paramagnetic organic components for the design of molecule-based magnets.[7]
The goal of this article is to elaborate an expedient strategy for the synthesis of
5-acylethynylpyrrole-2-carbaldehydes. For this, we have further developed the
transition-metal-free topochemical mechanoactivated ethynylation of the pyrrole
ring in a solid Al2O3 medium[8] and applied this reaction to pyrrole-2-carbaldehydes.
However, under usual conditions of such ethynylation (room temperature, 1 h),
pyrrole-2-carbaldehydes 1a,b prove to be incapable of reacting with acylbromoacety-
lenes 2a–c, likely due to the strong electron-withdrawing effect of the aldehyde
group, which decreases the pyrrole ring nucleophilicity. After a few unsuccessful
attempts, we have managed to circumvent this fundamental hurdle by the acetal
protection of the aldehyde function, thus decreasing its electron-withdrawing power.
Our preliminary single-example testing[9] of whether protected (as 2-(5,5-dimethyl-
1,3-dioxan-2-yl)-1H-pyrroles 3a,b) pyrroles can be ethynylated by acylbromoacety-
lenes in a solid Al2O3 medium under topochemical mechanoactivation appeared to
be positive and hence this strategy could be further developed to a general one.
Here we report a newly developed expedient strategy for the synthesis of
5-acylethynylpyrrole-2-carbaldehydes 4a–f using the acetal protection.
RESULTS AND DISCUSSION
Realization of the strategy starts from the reaction of pyrrole-2-carbaldehydes
1a,b with 2,2-dimethylpropanediol in the presence of para-toluene sulfonic acid
(PTSA) to give the corresponding cyclic acetals 3a,b. The latter are subjected to topo-
chemical mechanoactivated reaction with acylbromoacetylenes 2a–c in the alumina
medium without solvent, which leads to the expected ethynylated pyrroles 5a–f with
protected aldehyde function (Table 1). The deprotection has been implemented upon

SYNTHESIS OF 5-ACYLETHYNYLPYRROLE-2-CARBALDEHYDES
3
Table 1. Cross-coupling of pyrroles 1a,b with acylbromoacetylenes 2a–c with subsequent deprotection of
acetal 5a–f
Ethynylpyrroles 5a–f
Yield (%)
Ethynylpyrroles 4a–f
Yield (%)
54
77
41
43
54
50
41
87
75
84
81
89
stirring of acetals 5a–f in aqueous acetone at room temperature in the presence of
HCl, thus releasing the targeted ethynylated pyrrolecarbaldehydes 4a–f in 75–89%
total yields. Their general structure was proved by X-ray crystallographic analysis
of exemplar compound 4b (Fig. 1).
The key step of this strategy, the cross coupling of acetals 3a,b with acylbromoa-
cetylenes 2a–c, proceeds smoothly at room temperature for about 6 h on grinding the
reactants with Al2O3 powder. The synthesis is carried out in air and does not require

4
D. N. TOMILIN ET AL.
Figure 1. X-ray structure of 5-(3-(furan-2-yl)-3-oxoprop-1-ynyl)-1H-pyrrole-2-carbaldehyde (4b).
Thermal ellipsoids set at 50% probability.
Scheme 1. Possible side products 6–8.
argon protection. Conversion of reactants 2 and 3 and the extent of ethynylation
1
product 5 formation were monitored by H NMR spectroscopic analysis of the
CDCl3 extracts from the reaction mixture. Products 4a–f were isolated and purified
chromatographically. The solid reaction mixture was placed on the top of an
Al2O3-packed column and successively eluted with n-hexane and diethyl ether.
The reaction is chemo- and regioselective. The anticipated intermediates,[8b]
2-(1-bromo-2-acylethenyl)pyrroles 6, and side products 7 as well as 3-ethynylated
pyrroles 8 are not detected in the reaction mixtures (Scheme 1).
In some case, insignificant deprotection (5–6%) of both pyrroleacetals 3a,b and
ethynylated products 5a–f occurs. This can be spotted during the ethynylation and
upon chromatographical isolation. In the example of acetal 3a, it was shown that
instead of Al2O3, solid K2CO3 can also be applied as an active surface, though the
yield of the target product was 20% less than that obtained with alumina.
CONCLUSION
In conclusion, an expedient transition-metal-free strategy for the synthesis of
inaccessible functionalized pyrroles with reactive substituents, 5-acylethynylpyrrole-
2-carbaldehydes, has been elaborated. The key step of the strategy is topochemical

SYNTHESIS OF 5-ACYLETHYNYLPYRROLE-2-CARBALDEHYDES
5
mechanoactivated ethynylation of acetal-protected pyrrole-2-carbaldehydes with
acylbromoacetylenes in a solid Al2O3 medium. The synthesized compounds represent
novel building blocks for the preparation of stable organic radicals and polyradicals,
paramagnetic organic components for the design of molecule-based magnets, and a
variety of pyrrolic systems.
EXPERIMENTAL
IR spectra were obtained with a Bruker Vertex 70 spectrometer (400–4000 cmꢀ1
,
KBr pellets). 1H (400.1 MHz) and 13C NMR (100.6 MHz) spectra were recorded with
a Bruker DPX-400 instrument. Elemental analyses were recorded with an EA FLASH
1112 series (CHNS Analyzer) instrument. The determination of the unit cell and the
data collection for 5-(3-(furan-2-yl)-3-oxoprop-1-ynyl)-1H-pyrrole-2-carbaldehyde
(4b) was performed on a Bruker D8 Venture Photon 100 CMOS diffractometer with
MoKa radiation (k ¼ 0.71073) at 100(2) K using the x–2h scan technique. A specimen
of C12H7N1O3, approximate dimensions 0.118 × 0.145 × 0.282 mm, was used for the
X-ray crystallographic analysis. The X-ray intensity data were measured. The inte-
gration of the data using a monoclinic unit cell with P21=n space group yielded a total
of 38567 reflections to a maximum h angle of 30.09° (0.71 Å resolution), of which 2894
were independent (average redundancy 13.327, completeness ¼ 99.9%, Rint ¼ 7.06%,
Rsig ¼ 3.47%) and 2162 (74.71%) were greater than 2r(F2). The final cell constants of
a ¼ 6.4543(3) Å, b ¼ 13.5519(7) Å, c ¼ 11.5474(5) Å, b ¼ 101.922(2)°, and volume
¼ 988.24(8) Å3 are based upon the refinement of the XYZ-centroids of 9923 reflec-
tions above 20 r(I) with 4.693° < 2h < 59.68°. Data were corrected for absorption
effects using the multiscan method (SADABS). The ratio of minimum to maximum
apparent transmission was 0.905. The calculated minimum and maximum trans-
mission coefficients (based on crystal size) are 0.9710 and 0.9880. The structure was
solved and refined using the Bruker SHELXTL software package.[10]
Pyrrole-2-carbaldehydes 1a,b are commercial products (Aldrich).
2-(5,5-Dimethyl-1,3-dioxan-2-yl)-1H-pyrroles 3a,b were obtained according
to the procedure reported earlier.[11] Acylbromoacetylenes 2a–c were obtained by
bromination[12] of acylacetylenes synthesized by the method.[13]
Synthesis of Ethynylpyrroles 5a–f: General Procedure
Acetal 3a,b (1.821 mmol) and acylbromoacetylene 2a–c (1.821 mmol) were
carefully ground together with alumina (10-fold amount by weight) for 5 min and
allowed to stay at rt for 6 h. Then the solid reaction mixture was placed on the
top of an Al2O3-packed column and successively eluted with n-hexane and systems
of n-hexane with diethyl ether (hexane=diethyl ether with gradient from 3:1, 1:1,
1:3) to afford ethynylpyrroles 5a–f.
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1H-pyrrol-2-yl]-1-phenylprop-2-
yn-1-one (5a)
Yield: 304 mg (54%); grey needles; mp 141–143 °C. Anal. calcd. for C19H19NO3:
C, 73.77; H, 6.19; N, 4.53%. Found: C, 73.48; H, 6.16; N, 4.51. IR (KBr): 3314 (NH),

6
D. N. TOMILIN ET AL.
1
2174 (CꢁC), 1625 (CO) cmꢀ1. H NMR (400.1 MHz, CDCl3): d ¼ 9.09 (1H, br. s,
NH), 8.18–8.16 (2H, m, Ho Ph), 7.63–7.59 (1H, m, Hp Ph), 7.52–7.48 (2H, m, Hm
Ph), 6.82 (1H, dd, J ¼ 2.7, 3.4 Hz, H-3), 6.29 (1H, dd, J ¼ 2.9, 3.4 Hz, H-4), 5.50
(1H, s, O-CH-O), 3.76 (2H, d, J ¼ 11.2 Hz, CH2), 3.64 (2H, d, J ¼ 11.2 Hz, CH2),
1.26 (3H, s, Me), 0.81 (3H, s, Me). 13C NMR (100.6 MHz, CDCl3): d ¼ 177.7
=
(C O), 137.0 (Ci), 134.6 (C-5), 134.0 (Cp), 129.5 (Co), 128.7 (Cm), 121.1 (C-3),
109.8 (C-2), 108.5 (C-4), 96.1 (O-CH-O), 91.9 (ꢁC), 88.1 (Cꢁ), 77.5 (CH2-O), 30.5
(Me2C), 23.1 (Me), 22.0 (Me).
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1H-pyrrol-2-yl]-1-(furan-2-yl)
prop-2-yn-1-one (5b)
Yield: 223 mg (41%); yellow crystals; mp 142–146 °C. Anal. calcd. for
C17H17NO4: C, 68.21; H, 5.72; N, 4.68%. Found: C, 68.48; H, 5.56; N, 4.61. IR
1
(KBr): 3206 (NH), 2174 (CꢁC), 1612 (CO) cmꢀ1. H NMR (400.1 MHz, C6D6): d
¼ 8.72 (1H, br. s, NH), 7.05 (1H, dd, J ¼ 0.7, 3.5 Hz, H-5 furan), 6.90 (1H, dd,
J ¼ 0.7, 1.7 Hz, H-3 furan), 6.66 (1H, dd, J ¼ 1.6, 3.6 Hz, H-3), 6.29 (1H, dd, J ¼ 1.7,
3.5 Hz, 1H, H-4 furan), 5.83 (1H, dd, J ¼ 1.6, 3.6 Hz, H-4), 5.09 (1H, s, O-CH-O),
3.39 (2H, d, J ¼ 10.8 Hz, CH2), 3.15 (2H, d, J ¼ 10.8 Hz, CH2), 1.05 (3H, s, Me),
0.33 (3H, s, Me). 13C NMR (100.6 MHz, C6D6): d ¼ 164.5 (C O), 153.9 (C-2 furan),
=
147.0 (C-5 furan), 135.1 (C-5), 120.8 (C-3 furan), 118.9 (C-3), 112.4 (C-4 furan),
110.0 (C-2), 108.5 (C-4), 96.3 (O-CH-O), 91.7 (ꢁC), 86.8 (Cꢁ), 77.0 (CH2-O), 30.1
(Me2C), 23.0 (Me), 21.6 (Me).
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1H-pyrrol-2-yl]-1-(thiophen-2-yl)
prop-2-yn-1-one (5c)
Yield: 247 mg (43%); yellow crystals; mp 141–143 °C. Anal. calcd. for
C17H17NO3S: C, 64.74; H, 5.43; N, 4.44; S, 10.17%. Found: C, 64.58; H, 5.66; N,
4.21; S, 10.01. IR (KBr): 3314 (NH), 2175 (CꢁC), 1605 (CO) cmꢀ1
.
1H NMR
(400.1 MHz, CDCl3): d ¼ 8.97 (1H, br. s, NH), 7.94 (1H, dd, J ¼ 1.2, 3.8 Hz, H-3 thio-
phene), 7.70 (1H, dd, J ¼ 1.2, 4.9 Hz, H-5 thiophene), 7.18 (1H, dd, J ¼ 3.8, 4.9 Hz,
1H, H-4 thiophene), 6.79 (1H, dd, J ¼ 2.4, 3.8 Hz, H-4), 6.28 (1H, dd, J ¼ 2.4,
3.8 Hz, H-3), 5.49 (1H, s, O-CH-O), 3.75 (2H, d, J ¼ 10.8 Hz, CH2), 3.63 (2H, d,
J ¼ 10.8 Hz, CH2), 1.26 (3H, s, Me), 0.81 (3H, s, Me). 13C NMR (100.6 MHz, CDCl3):
=
d ¼ 168.6 (C O), 144.0 (C-2 thiophene), 133.8 (C-5 thiophene), 133.7 (C-3 thiophene),
133.6 (C-5), 127.4 (C-4 thiophene), 120.0 (C-3), 108.7 (C-2), 107.4 (C-4), 95.0 (O-CH-
O), 90.2 (ꢁC), 86.0 (Cꢁ), 76.5 (CH2-O), 29.5 (Me2C), 22.1 (Me), 21.0 (Me).
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1-ethyl-1H-pyrrol-2-yl]-1-
phenylprop-2-yn-1-one (5d)
Yield: 331 mg (54%); yellow crystals; mp 70–72 °C. Anal. calcd. for
C21H23NO3: C, 74.75; H, 6.87; N, 4.15%. Found: C, 74.62; H, 6.98; N, 4.18. IR
(KBr): 2171 (CꢁC), 1624 (CO) cmꢀ1
.
1H NMR (400.1 MHz, CDCl3): d ¼ 8.17
(2H, m, Ho Ph), 7.63–7.59 (1H, m, Hp Ph), 7.52–7.49 (2H, m, Hm Ph), 6.78 (1H,
d, J ¼ 4.0 Hz, H-3), 6.30 (1H, d, J ¼ 4.0 Hz, H-4), 5.47 (1H, s, O-CH-O), 4.39 (2H,

SYNTHESIS OF 5-ACYLETHYNYLPYRROLE-2-CARBALDEHYDES
7
q, J ¼ 7.2 Hz, NCH2), 3.78 (2H, d, J ¼ 10.8 Hz, CH2), 3.62 (2H, d, J ¼ 10.8 Hz, CH2),
1.48 (3H, t, J ¼ 7.2 Hz, MeCH2), 1.30 (3H, s, Me), 0.81 (3H, s, Me). 13C NMR
=
(100.6 MHz, CDCl3): d ¼ 177.4 (C O), 137.3 (Ci), 134.4 (C-5), 133.8 (Cp), 129.3
(Co), 128.7 (Cm), 120.4 (C-3), 113.5 (C-2), 109.8 (C-4), 97.1 (O-CH-O), 94.8 (ꢁC),
87.5 (Cꢁ), 78.0 (CH2-O), 41.7 (NCH2), 30.3 (Me2C), 23.3 (Me), 22.0 (Me), 16.7
(MeCH2).
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1-ethyl-1H-pyrrol-2-yl]-1-(furan-2-
yl)prop-2-yn-1-one (5e)
Yield: 298 mg (50%); yellow crystals; mp 68–70 °C. Anal. calcd. for C19H21NO4:
C, 69.71; H, 6.47; N 4.28%. Found: C, 69.79; H, 6.67; N, 4.20. IR (KBr): 2177 (CꢁC),
1626 (CO) cmꢀ1. 1H NMR (400.1 MHz, CDCl3): d ¼ 7.65 (1H, dd, J ¼ 0.7, 1.7 Hz, H-5
furan), 7.32 (1H, dd, J ¼ 0.7, 3.5 Hz, H-3 furan), 6.75 (1H, d, J ¼ 3.4 Hz, H-3),
6.59 (1H, dd, J ¼ 1.7, 3.5 Hz, H-4 furan), 6.28 (1H, d, J ¼ 3.4 Hz, H-4), 5.46 (1H, s,
O-CH-O), 4.36 (2H, q, J ¼ 7.0 Hz, NCH2), 3.77 (2H, d, J ¼ 10.8Hz, CH2), 3.63
(2H, d, J ¼ 10.8 Hz, CH2), 1.46 (3H, t, J ¼ 7.0 Hz, MeCH2), 1.30 (3H, s, Me), 0.81
13
=
(3H, s, Me). C NMR (100.6 MHz, CDCl3): d ¼ 164.6 (C O), 153.4 (C-2 furan),
147.5 (C-5 furan), 134.5 (C-5), 120.3 (C-3), 119.3 (C-3 furan), 113.3 (C-2), 112.6
(C-4 furan), 109.8 (C-4), 97.1 (O-CH-O), 93.9 (ꢁC), 86.6 (Cꢁ), 78.0 (CH2-O), 41.6
(NCH2), 30.3 (Me2C), 23.3 (Me), 22.0 (Me), 16.7 (CH2Me).
3-[5-(5,5-Dimethyl-1,3-dioxan-2-yl)-1-ethyl-1H-pyrrol-2-yl]-1-
(thiophen-2-yl)prop-2-yn-1-one (5f)
Yield: 256 mg (41%); yellow crystals; mp 88–90 °C. Anal. calcd. for
C19H21NO3S: C, 66.45; H, 6.16; N 4.08; S, 9.34%. Found: C, 66.18; H, 6.12; N,
4.20; S, 9.02. IR (KBr): 2175 (CꢁC), 1610 (CO) cmꢀ1
.
1H NMR (400.1 MHz,
CDCl3): d ¼ 7.92 (1H, dd, J ¼ 1.2, 3.8 Hz, H-3 thiophene), 7.69 (1H, dd, J ¼ 1.2,
4.9 Hz, H-5 thiophene), 7.17 (1H, dd, J ¼ 3.8, 4.9 Hz, H-4 thiophene), 6.77 (1H, d,
J ¼ 3.8 Hz, H-3), 6.29 (1H, d, J ¼ 3.8 Hz, H-4), 5.46 (1H, s, O-CH-O), 4.38 (2H, q,
J ¼ 7.0 Hz, NCH2), 3.78 (2H, d, J ¼ 10.8 Hz, CH2), 3.63 (2H, d, J ¼ 10.8 Hz, CH2),
1.48 (3H, t, J ¼ 7.0 Hz, MeCH2), 1.30 (3H, s, Me), 0.81 (3H, s, Me). 13C NMR
=
(100.6 MHz, CDCl3): d ¼ 169.2 (C O), 145.1 (C-2 thiophene), 134.5 (C-3 thiophene),
134.4 (C-5), 133.8 (C-5 thiophene), 128.3 (C-4 thiophene), 120.4 (C-3), 113.2 (C-2),
109.8 (C-4), 97.0 (O-CH-O), 94.0 (ꢁC), 86.0 (Cꢁ), 77.9 (CH2-O), 41.6 (NCH2),
30.3 (Me2C), 23.2 (Me), 21.9 (Me), 16.8 (CH2Me).
Synthesis of 5-Ethynylpyrrole-2-carbaldehydes 4a–f: General
Procedure
A solution of pyrrole 5a–f (2.295 mmol) in acetone (30 ml) was added to a 4 M
solution of HCl (9.5 ml) in acetone (20 ml) and the mixture was stirred at room
temperature for 1 h. Then diethyl ether was added (50 ml) and resulting solution
was washed twice by saturated NaCl and 5% NaHCO3 solutions and then dried over
K2CO3. Residue after removing solvent was purified by flash chromatography on
Al2O3 (eluents: n-hexane, hexane=diethyl ether with gradient from 3:1, 1:1, 1:3) to
give pyrroles 4a–f.

8
D. N. TOMILIN ET AL.
5-(3-Oxo-3-phenylprop-1-ynyl)-1H-pyrrole-2-carbaldehyde (4a)
Yield: 394 mg (77%); grey solid; mp 197–199 °C. Anal. calcd. for C14H9NO2:
C, 75.33; H, 4.06; N, 6.27%. Found: C, 75.56; H, 4.19; N, 6.09. IR (KBr): 3230
1
(NH), 2194 (CꢁC), 1662 (HCO), 1630 (COPh) cmꢀ1. H NMR (400.1 MHz, acet-
=
one-d6): d ¼ 12.06 (1H, br. s, NH), 9.66 (1H, s, HC O), 8.22–8.21 (2H, m, Ho Ph),
7.72–7.69 (1H, m, Hp Ph), 7.59–7.56 (2H, m, Hm Ph), 7.09 (1H, dd, J ¼ 2.7,
3.4 Hz, H-4), 6.98 (1H, dd, J ¼ 2.9, 3.4 Hz, H-3). 13C NMR (100.6 MHz, acetone-
=
=
d6): d ¼ 180.5 (HC O), 177.5 (C O), 137.7 (Ci), 136.8 (C-2), 135.4 (Cp), 130.3 (Co,
C-3), 129.9 (Cm), 121.7 (C-4), 120.6 (C-5), 91.6 (ꢁC), 85.3 (Cꢁ).
5-[3-(Furan-2-yl)-3-oxoprop-1-ynyl]-1H-pyrrole-2-carbaldehyde (4b)
Yield: 425 mg (87%); yellow crystals; mp 168–170 °C. Anal. calcd. for
C12H7NO3: C, 67.61; H, 3.31; N, 6.57%. Found: C, 67.29; H, 3.07; N, 6.34. IR
(KBr): 3240 (NH), 2207 (CꢁC), 1658 (HCO), 1628 (CO) cmꢀ1
.
1H NMR
=
(400.1 MHz, CDCl3): d ¼ 9.69 (1H, br. s, NH), 9.61 (1H, s, HC O), 7.72 (1H, dd,
J ¼ 0.8, 1.7 Hz, H-5 furan), 7.43 (1H, dd, J ¼ 0.8, 3.6 Hz, H-3 furan), 6.98 (1H, dd,
J ¼ 2.5, 4.0 Hz, H-4), 6.85 (1H, dd, J ¼ 2.4, 4.0 Hz, H-3), 6.64 (1H, dd, J ¼ 1.7,
13
=
3.6 Hz, H-4 furan). C NMR (100.6 MHz, CDCl3): d ¼ 179.5 (HC O), 163.0
=
(C O), 153.1 (C-2 furan), 148.4 (C-5 furan), 134.9 (C-2), 121.2 (C-3 furan), 120.8
(C-3), 120.4 (C-4), 117.2 (C-5), 113.0 (C-4 furan), 91.0 (ꢁC), 82.9 (Cꢁ).
5-[3-Oxo-3-(thiophen-2-yl)prop-1-ynyl]-1H-pyrrole-2-carbaldehyde (4c)
Yield: 394 mg (75%); yellow solid; mp 185 °C. Anal. calcd. for C12H7NO2S:
C, 62.87; H, 3.08; N, 6.11; S, 13.99%. Found: C, 62.69; H, 3.11; N, 6.24; S, 14.15.
IR (KBr): 3251 (NH), 2195 (CꢁC), 1658 (HCO), 1617 (CO) cmꢀ1
.
1H NMR
(400.1 MHz, acetone-d6): d ¼ 12.02 (1H, br. s, NH), 9.65 (1H, s, H-CO), 8.17
(1H, dd, J ¼ 1.0, 3.8 Hz, H-3 thiophene), 8.02 (1H, dd, J ¼ 1.0, 4.9 Hz, H-5 thio-
phene), 7.28 (1H, dd, J ¼ 3.8, 4.9 Hz, H-4 thiophene), 7.09 (1H, d, J ¼ 3.9 Hz,
H-4), 6.94 (1H, d, J ¼ 3.9 Hz, H-3). 13C NMR (100.6 MHz, acetone-d6): d ¼ 180.5
=
=
(HC O), 169.4 (C O), 145.6 (C-2 thiophene), 137.0 (C-3,5 thiophene), 136.8
(C-2), 129.7 (C-4 thiophene), 121.6 (C-3), 120.5 (C-4), 117.3 (C-5), 90.9 (ꢁC),
83.7 (Cꢁ).
1-Ethyl-5-(3-oxo-3-phenylprop-1-ynyl)-1H-pyrrole-2-carbaldehyde (4d)
Yield: 484 mg (84%); yellow solid; mp 84–86 °C. Anal. calcd. for C16H13NO2:
C, 76.48; H, 5.21; N, 5.57%. Found: C, 76.19; H, 5.30; N, 5.21. IR (KBr): 2183
(CꢁC), 1662 (HCO), 1634 (CO) cmꢀ1
.
1H NMR (400.1 MHz, CDCl3): d ¼ 9.65
(1H, s, H-CO), 8.18–8.16 (2H, m, Ho Ph), 7.68–7.64 (1H, m, Hp Ph), 7.56–7.52
(2H, m, Hm Ph), 6.95 (1H, d, J ¼ 4.0 Hz, H-4), 6.81 (1H, d, J ¼ 4.0 Hz, H-3), 4.62
(2H, q, J ¼ 7.2 Hz, CH2), 1.45 (3H, t, J ¼ 7.2 Hz, CH3). 13C NMR (100.6 MHz,
=
=
CDCl3): d ¼ 179.8 (HC O), 177.2 (C O), 136.8 (Ci), 134.5 (Cp), 133.6 (C-2), 129.5
(Co), 128.9 (Cm), 123.2 (C-3), 120.8 (C-5), 119.7 (C-4), 94.9 (ꢁC), 83.0 (Cꢁ), 42.7
(CH2), 16.6 (CH3).

SYNTHESIS OF 5-ACYLETHYNYLPYRROLE-2-CARBALDEHYDES
9
1-Ethyl-5-[3-(furan-2-yl)-3-oxoprop-1-ynyl]-1H-pyrrole-2-
carbaldehyde (4e)
Yield: 448 mg (81%); yellow solid; mp 82–84 °C. Anal. calcd. for C14H11NO3: C,
69.70; H, 4.60; N, 5.81%. Found: C, 69.58; H, 4.88; N, 5.47. IR (KBr): 2178 (CꢁC),
1
1659 (HCO), 1620 (CO) cmꢀ1. H NMR (400.13 MHz, CDCl3): d ¼ 9.63 (1H, s,
H-CO), 7.71 (1H, dd, J ¼ 0.7, 1.7 Hz, H-5 furan), 7.38 (1H, dd, J ¼ 0.7, 3.5 Hz, H-3
furan), 6.93 (1H, d, J ¼ 4.2 Hz, H-4), 6.77 (1H, d, J ¼ 4.2 Hz, H-3), 6.63 (1H, dd,
J ¼ 1.7, 3.5 Hz, H-4 furan), 4.59 (2H, q, J ¼ 7.2 Hz, CH2), 1.42 (3H, t, J ¼ 7.2 Hz,
13
=
=
CH3). C NMR (100.6 MHz, CDCl3): d ¼ 179.7 (HC O), 164.0 (C O), 153.1 (C-2
furan), 148.2 (C-5 furan), 133.6 (C-2), 123.1 (C-3), 120.6 (C-5), 120.4 (C-4), 119.6
(C-3 furan), 113.0 (C-4 furan), 94.0 (ꢁC), 82.2 (Cꢁ), 42.6 (CH2), 16.6 (CH3).
1-Ethyl-5-[3-oxo-3-(thiophen-2-yl)prop-1-ynyl]-1H-pyrrole-2-
carbaldehyde (4f)
Yield: 525 mg (89%); yellow solid; mp 90–92 °C. Anal. calcd. for C14H11NO2S:
C, 65.35; H, 4.31; N, 5.44; S, 12.46%. Found: C, 65.21; H, 4.28; N, 5.15; S, 12.08. IR
(KBr): 2181 (CꢁC), 1663 (HCO), 1604 (CO) cmꢀ1. 1H NMR (400.13 MHz, CDCl3):
d ¼ 9.65 (1H, s, H-CO), 7.96 (1H, dd, J ¼ 1.0, 3.8 Hz, H-3 thiophene), 7.77 (1H, dd,
J ¼ 1.0, 4.9 Hz, H-5 thiophene), 7.22 (1H, dd, J ¼ 3.8, 4.9 Hz, H-4 thiophene), 6.94
(1H, d, J ¼ 4.2 Hz, H-4), 6.79 (1H, d, J ¼ 4.2 Hz, H-3), 4.61 (2H, q, J ¼ 7.2 Hz,
CH2), 1.44 (3H, t, J ¼ 7.2 Hz, CH3). 13C NMR (100.6 MHz, CDCl3): d ¼ 179.7
=
=
(HC O), 168.7 (C O), 144.5 (C-2 thiophene), 135.6 (C-3 thiophene), 134.6 (C-5
thiophene), 133.5 (C-2), 128.6 (C-4 thiophene), 123.1 (C-3), 120.6 (C-5), 119.7 (C-
4), 94.3 (ꢁC), 81.6 (Cꢁ), 42.6 (CH2), 16.6 (CH3).
FUNDING
The work was carried with financial support of the Russian Foundation of
Basic Research (Project No 14-03-32042)
SUPPLEMENTAL MATERIAL
Supplemental data for this article can be accessed on the publisher’s website.
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