One-pot synthesis of 2,3,5-substituted 1H-pyrroles via the reaction of terminal acetylenes with nitriles and EtAlCl2 catalyzed by Сp2TiCl2

Article abstract of DOI:10.1016/j.tet.2019.01.006

A new one pot method for the synthesis of 2,3,5-substituted 1H-pyrroles in moderate to good yields (58–77%) based on multicomponent reaction of terminal acetylenes with nitriles and EtAlCl₂ in the presence of Сp₂TiCl₂ cata

Full text of DOI:10.1016/j.tet.2019.01.006

Accepted Manuscript
One-pot synthesis of 2,3,5-substituted 1H-pyrroles via the reaction of terminal
acetylenes with nitriles and EtAlCl catalyzed by Сp TiCl
2
2
2
Leila O. Khafizova, Mariya G. Shaibakova, Nikita A. Rikhter, Tatyana V. Tyumkina,
Usein M. Dzhemilev
PII:
S0040-4020(19)30018-3
https://doi.org/10.1016/j.tet.2019.01.006
TET 30058
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 3 November 2018
Revised Date: 30 December 2018
Accepted Date: 5 January 2019
Please cite this article as: Khafizova LO, Shaibakova MG, Rikhter NA, Tyumkina TV, Dzhemilev UM,
One-pot synthesis of 2,3,5-substituted 1H-pyrroles via the reaction of terminal acetylenes with nitriles
and EtAlCl catalyzed by Сp TiCl , Tetrahedron (2019), doi: https://doi.org/10.1016/j.tet.2019.01.006.
2
2
2
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ACCEPTED MANUSCRIPT
Graphical Abstract
Leave this area blank for abstract info.
One-pot synthesis of 2,3,5-substituted 1H-pyrroles
via the reaction of terminal acetylenes with nitriles
and EtAlCl2 catalyzed by Сp2TiCl2
Leila O. Khafizova, Mariya G. Shaibakova,
Nikita A. Rikhter, Tatyana V. Tyumkina,
Usein M. Dzhemilev

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ACCEPTED MANUSCRIPT
One-pot synthesis of 2,3,5-substituted 1H-pyrroles via the reaction of
terminal acetylenes with nitriles and EtAlCl2 catalyzed by Сp2TiCl2
Leila O. Khafizova,* Mariya G. Shaibakova, Nikita A. Rikhter,
Tatyana V. Tyumkina, Usein M. Dzhemilev
Institute of Petrochemistry and Catalysis of Russian Academy of Sciences,
141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
Abstract
A new one pot method for the synthesis of 2,3,5-substituted 1H-pyrroles in moderate to good
yields (58-77%) based on multicomponent reaction of terminal acetylenes with nitriles and
EtAlCl2 in the presence of Сp2TiCl2 catalyst and metallic magnesium has been developed
.
The possible mechanistic pathway to substituted pyrroles is discussed.
Keywords: Titanium catalysis, Terminal acetylenes, Nitriles, Ethylaluminum dichloride, 2,3,5-
Substituted 1H-pyrroles
1. Introduction
The pyrrole ring is part of many important biologically active natural products such as
hemoglobin, chlorophyll, bile pigments, and vitamin B12, that participate in the processes of
oxygen transfer in living organisms, fixation of solar energy in plants, oxygen transport
processes and other life-supporting reactions.1 It is also one of the structural units of the most
important drugs, having anticancer, antitumor, and antibacterial diseases properties.2 Several
pyrrole derivatives are cholesterol lowering agents (atorvastatin or lipitor Lipitor®)3a and HIV
fusion inhibitors.3b Pyrrole derivatives are also applied for the preparation of semiconducting and
fluorescence materials.4
In the literature, there is a sufficiently large number of publications concerning the
synthesis and study of the properties of pyrroles and its their derivatives. Traditional methods
for the pyrrole synthesis include thermal transformations of enolized ketazines in the presence of
Lewis acids (Piloty-Robinson reaction),5 condensation of 1,4-dicarbonyl compounds with
primary amines (Paal−Knorr reaction),6 as well as multicomponent condensation of aldehydes
* Corresponding author. Tel./fax: +7 347 2842750.
E-mail address: khafizovaleila@gmail.com (L.O. Khafizova).

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with β-ketoesters in the presence of ammonia (Hantzsch reaction)7. It should be noted that, along
with the procedures listed, in the literature,8 various modifications of these methods are
presented.
Despite numerous publications devoted to various aspects of the synthesis and use of
pyrroles, interest in these studies is not weakened, and the development of efficient methods for
the synthesis of practically important pyrroles based on the use of available starting reagents and
catalysts is one of the important and promising directions of research.
Methods for the preparation of pyrroles using zirconium and titanium-containing reagents
are also known.9 Titanium-mediated reactions have been shown to be highly efficient for the
formation of carbon-carbon or carbon-heteroatom bonds, and therefore titanocycles are
important intermediates for further selective transformations.
Here, we report the one-pot and efficient synthesis of 2,3,5-substituted 1H-pyrroles via a
multicomponent reaction between terminal acetylenes and organic nitriles in the presence of
EtAlCl2, metallic Mg and the Cp2TiCl2 catalyst in moderate to good yields (58-77%).
2. Results and Discussion
Recently, we have shown that the reaction between substituted acetylenes, ЕtAlCl2, and
carboxylic acid esters in the presence of metallic Mg and the Cp2TiCl2 catalyst leads to the
formation of tetrasubstituted furans.910 In continuation of this research, as well as to investigate
into the possibilities of the above reaction, we have studied the reaction between terminal
acetylenes, EtAlCl2 and organic nitriles under Cp2TiCl2 catalysis.
Preliminary experiments have shown that the model reaction of oct-1-yne with EtAlCl2
and benzonitrile in the presence of metallic Mg (chloride ion acceptor a reducing agent) and the
Cp2TiCl2 catalyst under reaction conditions (oct-1-yne : [Al] : benzonitrile : Mg : [Ti] = 1 : 4 : 2 :
o
4 : 0.1, THF, 0 C, 8 h) affords 3-hexyl-2,5-diphenyl-1H-pyrrole 1a in 50% yield (based on the
initial benzonitrile) after alkaline hydrolysis of the reaction mixture (Scheme 1). Along with 1a,
we have identified tetraphenylpyrazine 2 (25%), which is formed as a result of the competing
reaction between benzonitrile and EtAlCl2 under Cp2TiCl2 catalysis.1011
Together with 1a and 2,
small amounts of 1,3,5-trihexylbenzene (1,3,5-THB) 3 were formed in the yield that did not
exceed 8% (based on the initial acetylene).

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Scheme 1. Reaction of oct-1-yne with benzonitrile and EtAlCl2 catalyzed by Cp2TiCl2 in
tetrahydrofuran
To improve the selectivity of the above reaction, we have estimated the effect of the
solvent nature, catalyst concentration, and temperature of the reaction on the yield and content of
the products formed in the reaction. It is interesting to note that the use of a mixture of solvents
(tetrahydrofuran-hexane) allowed increasing the yield of 3-hexyl-2,5-diphenyl-1H-pyrrole 1a.
Thus, in a 3:1 mixture of THF/hexane, the yield of 1a increased to 75%, and tetraphenylpyrazine
2 was detected only in trace amounts (Scheme 2). The amount of the catalyst has a significant
effect on the yield of pyrrole 1a. Thus, the highest yield of 1a occurred at Cp2TiCl2
concentration of 10 mol% at ~ 0 °C. As the catalyst concentration decreases to 1 mol%, the yield
of 1a is reduced to 10%, which is probably due to a decrease in the concentration of catalytically
active centres in the reaction mass. With increase in catalyst concentration (more than 10 mol%),
the yield of the main reaction product remained unchanged.
Scheme 2. Reaction of oct-1-yne with benzonitrile and EtAlCl2 catalyzed by Cp2TiCl2 in a
mixture of THF-hexane (3:1)
The structure of the resulting 3-hexyl-2,5-diphenyl-1H-pyrrole 1a was determined using
spectroscopic analysis (13C and 1H NMR, IR) and mass spectrometry. In the 13C NMR spectrum,
the signals, assigned to the carbon atoms of the trisubstituted pyrrole ring, appear at 123.8, 129.3,

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108.3 and 131.5 ppm for the C(2), C (3), C(4), and C(5) atoms, respectively. The assignments
were made on the basis of homonuclear (COSY) and heteronuclear correlation (HSQC, HMBC)
experiments. Thus, based on the literature data,1112 the signal at δс 108.3 ppm was attributed to
the β-unsaturated carbon atom in the nitrogen-containing heterocyclic skeleton. The HSQC
spectrum demonstrates that there exists the correlation between this signal and the doublet at 6.5
ppm attributed to pyrrole ring proton. The spin-spin coupling constant, equal to 4.0 Hz, indicates
the existence of a long-range interaction with proton at the nitrogen atom, which is characteristic
for strongly bound states of aromatic systems. The long-range spin-spin coupling constant is also
observed in the COSY spectrum. Reliable signal assignments for С(3) and C(5) carbon atoms
were performed from the HMBC experiment, since the HMBC spectra contain cross peaks
between hydrogen and carbon atoms for H(4) − (3), H(4) − C (5), H(1ꞌ) – C(2) and H(1ꞌ) – C(4).
Fig. 1. Main COSY, HMBC correlation for 1a.
In analogous fashion, other terminal acetylenes (hex-1-yne, hept-1-yne, dec-1-yne,
phenylacetylene,
but-3-yn-1-yl-benzene),
as
well
as
cyclopropylacetylene
and
cyclopentylacetylene react with EtAlCl2 and benzonitrile in the presence of metallic Mg and the
o
Cp2TiCl2 catalyst (THF-hexane (3:1), 0 C) to afford the corresponding 2,3,5-substituted
pyrroles 1b-h in 67-77% yield (Scheme 3).
Scheme 3. Synthesis of 2,3,5-substituted 1H-pyrroles by the reaction of terminal acetylenes
with benzonitrile and EtAlCl2 catalyzed by Сp2TiCl2.

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The reaction is of a general nature, since, Other nitriles, for example, 2-
methylbenzonitrile, 4-methoxyphenylacetonitrile or 1-phenylcyclopropanecarbonitrile also
give 2,3,5-substituted pyrroles 3-5 (Scheme 4).
Me
Hex
CN
N
H
Me
Me
75%
58%
3
4
Hex
MeO
CN
MeO
OMe
Hex
Mg, Cp2TiCl2
THFꢀHexane
+
EtAlCl2
N
H
CN
Hex
N
H
5
72%
Scheme 4. Synthesis of 2,3,5-substituted 1H-pyrroles by the reaction of oct-1-yne with
aromatic nitriles and EtAlCl2 catalyzed by Сp2TiCl2.
On the basis of the data available in the literature, as well as our own experimental results,
we assume that the sequence of transformations to give substituted pyrroles (1a-h, 3-5) in the
reaction between terminal acetylenes, benzonitrile and EtAlCl2 catalyzed by Cp2TiCl2 initially
includes the formation of titanocene "Cp2Ti" 6 from Cp2TiCl2 and titanacyclopropene
intermediate 7.1213 The subsequent insertion of two molecules of the original nitrile into the
active Ti-C bonds in complex 7 yields diaminotitanacycloheptatriene 8. Transmetallation of the
intermediate 8 with EtAlCl2 results in diaminoaluminacycloheptatriene 9 with simultaneous
regeneration of the original catalyst Cp2TiCl2. Finally, hydrolysis and subsequent intramolecular
rearrangement of intermediate 9 lead to 2,3,5-substituted 1H-pyrroles 1a-h, 3-5 (Scheme 5).

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Scheme 5. Possible pathway for the formation of 2,3,5-substituted 1H-pyrroles from
terminal acetylenes, nitriles and ethylaluminum dichloride in the presence of the
Cp2TiCl2 catalyst.
3. Conclusion
Thus, we have developed a new efficient one-pot method for the synthesis of 2,3,5-
substituted 1H-pyrroles in moderate to good yields (58-77%). This approach allows producing
hard accessible and significant five-membered heterocycles in one preparative stage under
o
optimized reaction conditions (0 C, THF-hexane (3:1)) from terminal acetylenes and organic
nitriles in the presence of EtAlCl2 and the Cp2TiCl2 catalyst. Since the starting materials and
reagents required for this reaction are commercially available, the present synthesis is preferable
from a practical point of view. Further investigations into preparation of new heterocyclic
compounds using the developed method are currently in progress.
4. Experimental
4.1. General
Chromatographic analysis was performed on a Shimadzu GC-9A instrument using a 2000×2
mm column, the SE-30 (5 %) stationary phase on Сhromaton N-AW-HMDS (0.125-0.160 mm),

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helium carrier gas (30 mL/min), temperature programming from 50 to 300 оС at a 8 оС/min rate.
The 1Н and 13С 31P NMR spectra were measured in CDCl3 on a Bruker Avance-400 spectrometer
1
(100.62 MHz for 13C, 400.00 MHz for H). Elemental analysis (C, H) of the samples was
performed using an elemental analyzer (KCarlo Erba, model 1106). The mass spectra were
recorded on a Finnigan 4021 instrument (HP-5 glass capillary column, 50 000 х 0.25 mm; carrier
gas helium; oven temperature programming from 50 to 300 °C at a rate of 5 deg/min, evaporator
temperature 280 °C, the temperature of the ion source 250 °C [EI, 70 eV]). TLC was performed
on Silufol UV-254 plates with hexane–ethyl acetate (100:3-10) mixture as the eluent and I2 for
visualization. For column chromatography, Acros silica gel (0.060–0.200 mm) was used.
Reactions with organometallic compounds were performed in a dry argon flow. The solvents
were dried and distilled immediately prior to use. Commercially available terminal acetylenes,
Cp2TiCl2 and Et2AlCl2 (Aldrich) were used.
4.2.Reaction of terminal acetylenes with nitriles and EtAlCl2 catalyzed by Cp2TiCl2 (general
procedure)
A 100 mL glass reactor equipped with a magnetic stirrer under a dry argon atmosphere at 0
○C, was charged under stirring with THF (45 mL), EtAlCl2 (5,6 mL, 40 mmol), Mg (0,96 g, 40
mmol, powdered) and the Cp2TiCl2 catalyst (0,248 g, 1.0 mmol). After 1 h, hexane (15 mL),
acetylene (5 10 mmol) and nitrile (10 20 mmol) were added. The mixture was stirred for
additional 7 h. After the addition of Et2O (15 mL), the mixture was treated with 0.1 M aq NaOH
(10 mL). The organic layer was separated, and the aqueous layer was extracted with Et2O (3 x 25
mL). Сombined organic layers were dried over MgSO4. Solvent was evaporated and the residue
was purified by column chromatography on silica gel using a mixture of hexane and ethyl acetate
as eluent.
4.2.1. 3-Hexyl-2,5-diphenyl-1H-pyrrole (1a)
Rf 0.56, (hexanes/EtOAc = 100:3), yellow oil (yield 75 %, 1136 mg). IR (neat): 3442,
1
3059, 2954, 2925, 2856, 1606, 1519, 1456, 1265, 758, 695cm-1. H NMR (400 MHz, CDCl3): δ
0.91 (t, J = 8 Hz, 3H, CH3), 1.33-1.42 (m, 6H, CH2), 1.69 (pent guint, J = 8 Hz, 2H, CH2), 2.67
(t, J = 8 Hz, 2H, CH2), 6.52 (d, J = 4 Hz, 1H, CH), 7.23-7.54 (m, 10H, CH(Ar)), 8.28 (s, 1H, NH).
13C NMR (400 MHz, CDCl3): δ 14.11, 22.67, 26.58, 29.37, 31.11, 31.78, 108.33, 123.61,
123.77, 126.11, 126.33, 126.77, 128.77, 128.89, 129.31, 131.54, 132.57, 133.56. MS, m/z: 303
(М+). Anal. Calcd for C22H25N: C 87.08, H 8.30, N 4.62. Found: C 87.03, H 8.21.

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4.2.2. 3-Butyl-2,5-diphenyl-1H-pyrrole (1b).
Rf 0.45, (hexanes/EtOAc = 100:4), yellow oil (yield 74%, 1017 mg). IR (neat): 3442,
1
3059, 2955, 2927, 2857, 1606, 1493, 1455, 1264, 1073, 757, 694 cm-1. H NMR (400 MHz,
CDCl3): δ 0.96 (t, J = 8Hz, 3H, CH3), 1.42-1.47 (m, 2H, CH2), 1.68 (pent guint, J = 8 Hz, 2H,
CH2), 2.68 (t, 2H, J = 8 Hz, 2H, CH2), 6.53 (s, 1H, CH), 7.23-7.54 (m, 10H, CH(Ar)), 8.28 (s, 1H,
NH). 13C NMR (400 MHz, CDCl3): δ 14.04, 22.74, 26.27, 33.34, 108.35, 123.60, 123.71,
126.12, 126.34, 126.77, 128.77, 128.89, 129.32, 131.54, 132.56, 133.56. MS, m/z: 275 (М+).
Anal. Calcd for C20H21. N: C 87.23, H 7.69, N 5.09. Found: C 87.12, H 7.77.
4.2.3. 3-Pentyl-2,5-diphenyl-1H-pyrrole (1c).
Rf 0.50, (hexanes/EtOAc = 100:3), slight yellow oil (yeild 77%, 1113 mg). IR (neat):
1
3441, 3060, 2954, 2926, 2856, 1670, 1606, 1493, 1455, 1262, 759, 695 cm-1. H NMR (400
MHz, CDCl3): δ 0.92 (t, J = 8Hz, 3H, CH3), 1.28, (m, 2H, CH2), 1.38 (m, 2H, CH2), 1.70 (pent
guint, J = 8 Hz, 2H, CH2), 2.67 (t, J = 8 Hz, 2H, CH2), 6.53 (s, 1H, CH), 7.23-7.54 (m, 10H,
CH(Ar)), 8.29 (s, 1H, NH). 13C NMR (400 MHz, CDCl3): δ 14.10, 22.61, 26.55, 30.83, 31.91,
108.33, 123.61, 123.75, 126.11, 126.33, 126.77, 128.76, 128.88, 129.53, 131.62, 132.56, 133.47.
MS, m/z: 289 (М+). Anal. Calcd for C21H23N: C 87.15, H 8.01, N 4.84. Found: C 87.04, H 7.89.
4.2.4. 3-Octyl-2,5-diphenyl-1H-pyrrole (1d).
Rf 0.55, (hexanes/EtOAc = 100:3), yellow oil (yield 72 %, 1191 mg). IR (neat): 3437,
1
3060, 2924, 2853, 1605, 1493, 1455, 1287, 759, 695 cm-1. H NMR (400 MHz, CDCl3): δ 0.91
(m, 3H, CH3), 1.24-1.42 (m, 10H, CH2), 1.69 (m, 2H, CH2), 2.68 (t, J = 8 Hz, 2H, CH2), 6.53 (s,
13
1H, CH), 7.21-7.54 (m, 10H, CH(Ar)), 8.29 (s, 1H, NH). C NMR (400 MHz, CDCl3): δ 14.13,
22.70, 26.58, 29.32, 29.53, 29.70, 31.15, 31.92, 108.34, 123.62, 123.77, 126.11, 126.33, 126.78,
128.77, 128.89, 129.32, 131.64, 132.58, 133.58. MS, m/z: 331 (М+). Anal. Calcd for C24H29N: C
86.96, H 8.82, N 4.23. Found: C 86.72, H 8.39.
4.2.5. 3-Cyclopropyl-2,5-diphenyl-1H-pyrrole (1e).
Rf 0.55, (hexanes/EtOAc = 100:1), yellow oil (yield 74%, 958 mg). IR (neat): 3440, 3058,
2956, 2925, 2855, 1668, 1605, 1495, 1455, 1263, 760, 695 cm-1. 1H NMR (400 MHz, CDCl3): δ
0.70 (m, 2H, CH2), 0.94 (m, 2H, CH2), 1.99 (m, 1H, CH), 6.29 (s, 1H, CH), 7.23-7.67 (m, 10H,
13
CH(Ar)), 8.32 (s, 1H, NH). C NMR (400 MHz, CDCl3): δ 8.18, 8.24, 105.50, 123.66, 125.16,
126.24, 126.43, 126.75, 128.90, 130.22, 131.53, 132.46, 133.31. MS, m/z: 259 (М+). Anal. Calcd
for C19H17N: C 87.99, H 6.61, N 5.40. Found: C 87.85, H 6.50.

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4.2.6. 3-Cyclopentyl-2,5-diphenyl-1H-pyrrole (1f).
Rf 0.50, (hexanes/EtOAc = 100:3), orange oil (yield 76%, 1091 mg). IR (neat): 3438,
1
3059, 2958, 2926, 2857, 1670, 1604, 1494, 1456, 1265, 758, 694 cm-1. H NMR (400 MHz,
CDCl3): δ 1.65-1.75 (m, 4H, C2,3,4,5HaHb),* 1.82-1.90 (m, 2H, C3,4HaHb), 2.02-2.10 (m, 2H,
C2,5HaHb), 3.15-3.22 (m, 1H, C1H), 6.57 (d, J = 4 Hz, 1H, CH), 7.22-7.54 (m, 10H, CH(Ar)), 8.24
(s, 1H, NH). 13C NMR (400 MHz, CDCl3): δ 25.64, 35.41, 37.00, 105.74, 123.62, 126.12,
126.52, 127.34, 127.84, 128.74, 128.87, 129.55, 131.83, 132.52, 133.65. MS, m/z: 287 (М+).
Anal. Calcd for C21H21N: C 87.76, H 7.36, N 4.87. Found: C 87.55, H 7.30.
*Diastereaotopic protons of the cyclopentyl substituent are designated as Ha (which exhibit
upfield signals) and Hb (which exhibit downfield signals). The numbering of carbons are given in
Supplementary materials.
4.2.7. 3-Phenyl-2,5-diphenyl-1H-pyrrole (1g).
Rf 0.65, (hexanes/EtOAc = 100:5), white solid, mp 126–128 °C, (yield 76 %, 1121 mg).
IR (neat): 3435, 3059, 3023, 2923, 2851, 1949, 1666, 1606, 1486, 1467, 1261, 1217, 1072, 955,
757, 696, 587 cm-1. 1H NMR (400 MHz, CDCl3): δ 6.75 (s, 1H, CH), 7.24-7.38 (m, 9H, CH(Ar)),
7.42-7.46 (m, 4H, CH(Ar)), 7.58-7.60 (m, 2H, CH(Ar)), 8.48 (s, 1H, NH). 13C NMR (400 MHz,
CDCl3): δ 108.61, 123.82, 124.03, 125.97, 126.55, 127.00, 127.52, 128.36, 128.44, 128.74,
129.01, 129.34, 132.25, 133.10, 134.92, 136.38. MS, m/z: 295 (М+). Anal. Calcd for C22H17N: C
89.46, H 5.80, N 4.74. Found: C 89.23, H 5.67.
4.2.8. 2,5-Diphenyl-3-(2-phenylethyl)-1H-pyrrole (1h).
Rf 0.58, (hexanes/EtOAc = 100:4), yellow solid, mp 136 –137 °C, (yeild 67 %, 1082 mg).
IR (neat): 3437, 3059, 3025, 2920, 2851, 1958, 1669, 1604, 1493, 1453, 1265, 1211, 1073,
1
907,804, 758, 696, 519 cm-1. H NMR (400 MHz, CDCl3): δ 3.01 (s, 4H, CH2), 6.57 (d, J = 4
Hz, 1H, CH), 7.23-7.34 (m, 9H, CH(Ar)), 7.39-7.45 (m, 4H, CH(Ar)), 7.53-7.55 (m, 2H, CH(Ar)),
8.32 (s, 1H, NH). 13C NMR (400 MHz, CDCl3): δ 28.77, 37.40, 108.21, 122.65, 123.66, 125.85,
126.23, 126.51, 126.83, 128.32, 128.49, 128.81, 128.94, 129.61, 131.66, 132.50, 133.35, 142.33.
MS, m/z: 323 (М+). Anal. Calcd for C24H21N: C 89.12, H 6.54, N 4.33. Found: C 89.01, H 6.39.
4.2.9. 2,3,5,6-Tetraphenylpyrazin (2).
Rf 0.54 (hexanes/EtOAc = 100:3), white solid, mp 247–248 °C,[10] (yeild 25 %, 240 mg). IR
(neat): 3460, 3445, 3083, 3059 2850, 1958, 1600, 1493, 1454, 1404, 1218,1128, 1075, 1028,
1
733, 695, 598 cm-1. H NMR (400 MHz, CDCl3): δ 7.28-7.36 (m, 12H, CH(Ar)), 7.68-7.65 (m,

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13
8H, CH(Ar)). C NMR (400 MHz, CDCl3): δ 128.23, 128.60, 129.89, 138.44, 148.42. MALDI
TOF/ TOF, m/z 385.1707 [M+H]+, Сalcd for C28H21N2 [M+H]+ 385.1711.
4.2.10. 3-Hexyl-2,5-bis(2-methylphenyl)-1H-pyrrole (3).
Rf 0.55, (hexanes/EtOAc = 100:3), white oil (yield 75 %, 1241 mg). IR (neat): 3442,
1
2925, 2855, 1949, 1606, 1519, 1456, 1286, 805, 695 cm-1. H NMR (400 MHz, CDCl3): δ 0.87
(t, J = 8Hz, 3H, CH3), 1.27-1.31 (m, 6H, CH2), 1.58 (pent guint, J = 8 Hz, 2H, CH2), 2.34 (s, 3H,
CH3), 2.42 (t, J = 8 Hz, 2H, CH2), 2.55 (s, 3H, CH3), 6.34 (d, J = 4 Hz, 1H CH), 7.18-7.42 (m,
8H, CH(ar)), 7.95 (s, 1H, NH). 13C NMR (400 MHz, CDCl3): δ 14.10, 20.33, 21.60, 22.67, 26.20,
29.18, 31.11, 31.73, 109.74, 122.93, 125.57, 126.02, 126.09, 126.31, 127.35, 127.67, 128.29,
130.23, 130.29, 131.01, 131.18, 132.84, 133.23, 134.48, 137.47. MS, m/z: 331 (М+). Anal. Calcd
for C24H29N: C 86.96, H 8.82, N 4.23. Found: C 86.75, H 8.70.
4.2.11. 3-Hexyl-2,5-bis(4-methoxybenzyl)-1H-pyrrole (4).
Rf 0.42, (hexanes/EtOAc = 100:10), yellow oil (yield 58 %, 1134 mg). IR (neat): 3440,
2922, 2855, 2830, 1950, 1612, 1520, 1455, 1284, 804, 696 cm-1. 1H NMR (400 MHz, CDCl3): δ
0.91 (t, J = 8Hz, 3H, CH3), 1.33-1.42 (m, 6H, CH2), 1.69 (pent guint, J = 8 Hz, 2H, CH2), 2.67 (t,
J = 8 Hz, 2H, CH2), 3.62 (s, 4H, CH2Ph), 3.82 (s, 36H, CH3), 6.52 (d, J = 4 Hz, 1H, CH), 6.88
(m, 4H, CH(ar)), 7.11 (m, 4H, CH(ar)), 7.28 (1H, NH). 13C NMR (400 MHz, CDCl3): δ 14.51,
22.67, 26.68, 29.37, 31.11, 31.82, 33.45, 55.75, 114.29, 126.35, 131.07, 132.36, 138.74, 143.90,
146.82, 159.76. MS, m/z: 391 (М+). Anal. Calcd for C26H33NО2: C 79.76, H 8.50, О 8.17, N
3.58. Found: C 79.57, H 8.37.
4.2.12. 3-Hexyl-2,5-bis(1-phenylcyclopropyl)-1H-pyrrole (5).
Rf 0.60, (hexanes/EtOAc = 100:2), yellow oil (yield 72 %, 1379 mg). IR (neat): 3460,
3443, 3084, 3059, 3007, 2955, 2927, 2855, 1682, 16060, 1495, 1462, 1379, 1261, 1026, 799,
1
699 cm-1. H NMR (400 MHz, CDCl3): δ 0.88 (t, J = 8Hz, 3H, CH3), 1.23-1.30 (m, 14H, CH2
(4CH2 cyclopropyl, 3CH2 alkyl)), 1.49 (pent guint, J = 8 Hz, 2H, CH2), 2.41 (t, J = 8 Hz, 2H, CH2),
13
5.77 (d, J = 4Hz, 1H, CH), 7.10-7.51 (m, 10H, CH(ar)), 7.99 (s, 1H, NH). C NMR (400 MHz,
CDCl3): δ 14.10, 16.68, 17.43, 21.03, 22.64, 23.59, 26.04, 29.53, 30.60, 31.77, 104.99, 122.38,
125.13, 125.25, 126.13, 127.91, 128.09, 128.37, 130.89, 134.03, 144.52, 146.07. MS, m/z: 383
(М+). Anal. Calcd for C28H33N: C 87.68, H 8.67, N 3.65. Found: C 87.50, H 8.58.
5. Acknowledgements

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This work was financially supported by the Russian Foundation for Basic Research (Grant
No. 17-43-020676). The structural studies were performed with the use of unique equipment in
“Agidel” Collective Usage Centre at the Institute of Petrochemistry and Catalysis of RAS.
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