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Short Note

4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-carbonitrile

1
A.E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Science, 1 Favorsky St., 664033 Irkutsk, Russia
2
Biomedical Research and Technology Department of the Irkutsk Scientific Centre of the Russian Academy of Science, 283B Lermontov St., 664033 Irkutsk, Russia
*
Author to whom correspondence should be addressed.
Molbank 2023, 2023(1), M1547; https://doi.org/10.3390/M1547
Received: 21 December 2022 / Revised: 9 January 2023 / Accepted: 10 January 2023 / Published: 12 January 2023

Abstract

:
The title compound, 4-amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)- 1H-pyrrole-3-carbonitrile, was synthesized for the first time in a 40% yield by the reaction of N-benzyl-3-imino-5,6,7,8-tetrahydro-3H-pyrrolo[1,2-a]indol-1-amine and 1-chloroacetophenone in a K2CO3/MeCN system (reflux, 6 h). The product was characterized by 1H-NMR, 13C-NMR, IR spectroscopy, and elemental analysis.

1. Introduction

4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-car-bonitrile 1 belongs to the class of 2,2′-bipyrroles, which are of interest as basic building blocks for the synthesis of pyrrolic macrocycles and natural products, such as prodigiosins, promising biomolecules with many potential applications [1,2]. 2,2′-Bipyrroles are extensively employed for the design of many synthetic porphyrinoids [3,4], which are used as anion binding agents [5], ion chemosensors [6], antitumor agents [7,8], and photosentizers for the photodynamic therapy (PDT) [9] as well as for conducting polymers [10]. 2,2′-Bipyrroles with electron-withdrawing benzoyl groups are highly polarized, which induces dipole−dipole interaction, π−π stacking, and hydrogen-bonding interaction leading to unique self-assemblies to functional materials [3,11,12]. Such features of bipyrroles impart interesting properties to porphyrinoids [13], and therefore their synthesis attracts ever-growing interest of the synthetic community. The methods for the preparation of 2,2′-bipyrroles, including the most common Ullmann coupling of α-halogenated pyrroles, Lewis-acid-catalyzed pyrrolinone condensation, and oxidative dimerization of pyrroles, are summarized in the reviews [1,3,4].

2. Result

4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-car-bonitrile (1) was synthesized according to our previously developed method [14,15] by the reaction of easily available 1-benzyl-3-imino-5,6,7,8-tetrahydro-3H-pyrrolo-[1,2-a]indol-1-amine (2) and 1-chloroacetophenone in K2CO3/MeCN system (reflux, 6 h) (Scheme 1). These conditions were proved to be suitable for the synthesis of the target product and ensured its yield of 40%.
The mechanism of compound 1 formation can be rationalized as depicted in Scheme 2. Initially, 1-benzyl-3-imino-5,6,7,8-tetrahydro-3H-pyrrolo[1,2-a]indol-1-amine (2) is alkylated with 1-chloroacetophenone to form the corresponding ketone A. The latter undergo the proton abstraction from the active CH2 group, then carbanion B thus obtained intramolecularly attacks the nitrile’s electrophilic carbon with simultaneous the pyrrolizine ring-opening and formation of iminopyrroline C with chiral center. Its further aromatization via the proton transfer from asymmetric carbon atom to imino-group finishes this process.
The structure and composition of the synthesized 2,2′-bipyrrole 1 were confirmed by 1H, 13C NMR, IR spectroscopy (see Supplementary Materials). Elemental analysis establishes the chemical formula of compound 1.
Thus, we synthesized new 2,2′-bipyrrole, 4-amino-5-benzoyl-1-benzyl-2- (4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-carbonitrile, which, in addition to the benzoyl group, has amino and nitrile functions located in neighboring positions. The obtain polyfunctionalized bipyrrole represents a possible intermediate for the synthesis of novel purine analogs that can further expand synthetic application of this compound.

3. Materials and Methods

NMR spectra were recorded on a Bruker DPX-400 spectrometer (Bruker, Billerica, MA, USA) (400.1 MHz for 1H and 100.6 MHz for 13C) in CDCl3. The internal standards were HMDS (for 1H) and the residual solvent signals (for 13C). Coupling constants (J) were measured from one-dimensional spectra, and multiplicities were abbreviated as follows: s (singlet), br. s (broad singlet), d (doublet), and m (multiplet). IR spectra were recorded on a two-beam Bruker Vertex 70 spectrometer (Bruker, Billerica, MA, USA), in a KBr pellet. Elemental analyses (C, H, N) were performed on an EA FLASH 1112 Series (CHN Analyzer) instrument (Thermo Finnigan, Italy). Melting points (uncorrected) were measured using a Stuart Scientific melting point SMP3 apparatus.
Synthesis of 4-amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)- 1H-pyrrole-3-carbonitrile (1). The mixture of 1-benzyl-3-imino-5,6,7,8-tetrahydro-3H-pyrrolo[1,2-a]indol-1-amine (2) (154 mg, 0.51 mmol), K2CO3 (95 mg, 0.61 mmol) and 1-chloroacetophenone (106 mg, 0.77 mmol) in MeCN (8 mL) was refluxed for 6 h. After cooling the reaction mixture to room temperature, the precipitate was filtered off and washed with MeCN (3 × 3 mL). The filtrate was concentrated under reduced pressure. By column chromatography of the residue (Al2O3, eluent n-hexane and systems of n-hexane/diethyl ether gradient from 4:1 to 1:4) 2,2′-bipyrrole 1 was obtained (84 mg, 40%) as yellow crystals, mp 198–200 °C (n-hexane). IR spectrum (KBr), ν, cm−1: 3476, 3414, 3339, 3229, 3080, 2923, 2849, 2218, 1601, 1570, 1499, 1463, 1430, 1367, 1293, 1237, 1148, 1076, 1004, 809, 738, 698. 1H NMR (CDCl3, ppm): δ 8.27 (br. s, 1H, NH), 7.49–7.45 (m, 3H, Ho,p, COPh), 7.41–7.37 (m, 2H, Hm, COPh), 7.21–7.18 (m, 3H, Hm,p, CH2Ph), 6.80–6.79 (m, 2H, Ho, CH2Ph), 6.26 (d, J = 2.1 Hz, 1H, H-3), 5.39 (s, 2H, CH2, CH2Ph), 4.51 (br. s, 2H, NH2), 2.57–2.54 (m, 2H, CH2-7), 2.47–2.44 (m, 2H, CH2-4), 1.82–1.76 (m, 2H, CH2-6), 1.74–1.68 (m, 2H, CH2-5). 13C NMR (CDCl3, ppm): 184.2 (C=O), 147.2 (C-4), 140.4 (Ci, PhCO), 140.2 (Cp), 137.5 (Ci, PhCH2), 132.3 (C-7a), 131.4 (Cp, PhCO), 128.9 (2C, m, PhCO), 128.7 (2C, m, PhCH2), 127.9 (2C, o, PhCO), 127.5 (Cp, PhCH2), 126.1 (2C, o, PhCH2), 119.8 (C-3a), 116.8 (CN), 116.7 (C-5), 115.8 (C-2′), 112.5 (C-3′), 80.9 (C-3), 51.2 (CH2Ph), 23.4, 23.0, 22.8, 22.7 (CH2-4,5,6,7). Anal. calcd. for C27H24N4O (%): C, 77.12; H, 5.75; N, 13.32. Found (%): C, 77.28; H, 5.57; N, 13.46.

Supplementary Materials

The followings can be downloaded online. Copies of 1H NMR, 13C NMR, IR spectra.

Author Contributions

Conceptualization, B.A.T. and L.N.S.; methodology, O.V.P. and V.V.K.; formal analysis, I.A.U.; data curation, L.N.S.; writing—original draft preparation, L.N.S. and O.V.P.; writing—review and editing, O.V.P., I.A.U. and L.N.S.; supervision, B.A.T. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funding by the Ministry of Education and Science of Russian Federation (State Registration No. 121021000199-6).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank the Baikal Analytical Centre of collective use.

Conflicts of Interest

The authors declare no conflict of interest.

References

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Scheme 1. Synthesis of 4-amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)- 1H-pyrrole-3-carbonitrile (1).
Scheme 1. Synthesis of 4-amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)- 1H-pyrrole-3-carbonitrile (1).
Molbank 2023 m1547 sch001
Scheme 2. Possible mechanism of 2,2′-bipyrrole 1 formation.
Scheme 2. Possible mechanism of 2,2′-bipyrrole 1 formation.
Molbank 2023 m1547 sch002
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MDPI and ACS Style

Petrova, O.V.; Ushakov, I.A.; Sobenina, L.N.; Kireeva, V.V.; Trofimov, B.A. 4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-carbonitrile. Molbank 2023, 2023, M1547. https://doi.org/10.3390/M1547

AMA Style

Petrova OV, Ushakov IA, Sobenina LN, Kireeva VV, Trofimov BA. 4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-carbonitrile. Molbank. 2023; 2023(1):M1547. https://doi.org/10.3390/M1547

Chicago/Turabian Style

Petrova, Olga V., Igor A. Ushakov, Lyubov N. Sobenina, Victoriya V. Kireeva, and Boris A. Trofimov. 2023. "4-Amino-5-benzoyl-1-benzyl-2-(4,5,6,7-tetrahydro-1H-indol-2-yl)-1H-pyrrole-3-carbonitrile" Molbank 2023, no. 1: M1547. https://doi.org/10.3390/M1547

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