Improved synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrroles a promising dye for organic electronic devices: An experimental and theoretical approach

Article abstract of DOI:10.1016/j.dyepig.2017.08.056

Pyrrolo-[3,2-b]pyrroles represent a class of promising materials for application in organic electronics with interesting optoelectronic properties and great synthesis versatility, but yields obtained from varied synthetic routes are still very low, hindering their effective application for industrial purposes. In this report, we present a method for the synthesis of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives by multicomponent reactions employing niobium pentachloride as a catalyst. The optical characterization of the products is also presented. Electronic structure calculations were performed to help the interpretation of the synthesis process, as well as the optical properties of the systems. Excellent yields and low reaction times were obtained, indicating that NbCl₅ is an efficient catalyst for such systems. The products show promising properties for optoelectronic applications that can be adjusted by the choice of benzaldehyde derivatives used in the synthesis.

Full text of DOI:10.1016/j.dyepig.2017.08.056

Accepted Manuscript
Improved synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrroles a promising dye for
organic electronic devices: An experimental and theoretical approach
Lucas Michelão Martins, Samuel de Faria Vieira, Gabriel Baldo Baldacim, Bruna
Andressa Bregadiolli, José Cláudio Caraschi, Augusto Batagin-Neto, Luiz Carlos da
Silva-Filho
PII:
S0143-7208(17)31351-7
10.1016/j.dyepig.2017.08.056
DYPI 6218
DOI:
Reference:
To appear in: Dyes and Pigments
Received Date: 13 June 2017
Revised Date: 14 August 2017
Accepted Date: 30 August 2017
Please cite this article as: Martins LucasMichelã, de Faria Vieira S, Baldacim GB, Bregadiolli
BA, Caraschi JoséClá, Batagin-Neto A, da Silva-Filho LC, Improved synthesis of tetraaryl-1,4-
dihydropyrrolo[3,2-b]pyrroles a promising dye for organic electronic devices: An experimental and
theoretical approach, Dyes and Pigments (2017), doi: 10.1016/j.dyepig.2017.08.056.
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ACCEPTED MANUSCRIPT
Improved synthesis of Tetraaryl-1,4-dihydropyrrolo[3,2-
b]pyrroles a promising dye for organic electronic devices: An
Experimental and Theoretical approach.
Lucas Michelão Martins,1 Samuel de Faria Vieira,2 Gabriel Baldo Baldacim,1
Bruna Andressa Bregadiolli,1 José Cláudio Caraschi,2 Augusto Batagin-Neto2
and Luiz Carlos da Silva-Filho1*
1
Laboratory of Organic Synthesis and Processes, Department of Chemistry, São Paulo State
University (UNESP) – School of Sciences, Av. Eng. Luiz Edmundo Carrijo Coube, 14-01,
17033-360 - Bauru, SP, Brazil.
2 São Paulo State University (UNESP), Campus Itapeva, Rua Geraldo Alckmin, 519, 18409-010
- Itapeva, SP, Brazil
* Corresponding author: E-mail: lcsilva@fc.unesp.br
Keywords: niobium pentachloride
•
heterocycles
•
fluorescence
•
multicomponent reactions • density functional calculations
Abstract: Pyrrolo-[3,2-b]pyrroles represent a class of promising materials for
application in organic electronics with interesting optoelectronic properties and
great synthesis versatility, but yields obtained from varied synthetic routes are
still very low, hindering their effective application for industrial purposes. In this
report, we present a method for the synthesis of tetraaryl-1,4-dihydropyrrolo-
[3,2-b]pyrrole derivatives by multicomponent reactions employing niobium
pentachloride as a catalyst. The optical characterization of the products is also
presented. Electronic structure calculations were performed to help the
interpretation of the synthesis process, as well as the optical properties of the
systems. Excellent yields and low reaction times were obtained, indicating that
NbCl5 is an efficient catalyst for such systems. The products show promising
1

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properties for optoelectronic applications that can be adjusted by the choice of
benzaldehyde derivatives used in the synthesis.
1.0 Introduction
Heteropentalenes belong to a class of heterocyclic compounds with two
fused pentagonal rings.[1] Derivatives with 10 π electrons are aromatic and have
been studied due to their potential use in electronic devices, such as solar
cells,[2] transistors,[3] and electrochromic devices.[4,5] Among the aromatic
heteropentalenes, those most frequently studied are the thieno[3,2-
b]thiophenes and thieno[3,2-b]pyrroles.[3,4,6-12]
In this context, dihidropyrrolo-[3,2-b]pyrrole derivatives have gained
increasing attention in recent years, mainly because of their high fluorescence
quantum yields and significant two-photon absorption (2PA) cross-sections.[13-15]
In addition, the pyrrolo[3,2-b]pyrrole structure has also been predicted as the
most efficient electron donor among the 10π electron systems, such as
thieno[3,2-b]thiophene and thieno[3,2-b]pyrrole.[16] Regarding optical properties,
it has been shown that some azapentalene derivatives present very broad
absorption spectra presenting colorations ranging from blue to red.[17-19]
Some works also show that the tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole
derivatives can be used as starting materials to synthesize other electron-rich
structures, including pentaaryl- and hexaaryl-1,4-dihydropyrrolo-[3,2-b]pyrroles,
diindolo[2,3-b:2’,3’-f]pyrrolo[3,2-b]pyrroles,
dihydropyrrolo[3,2-b]pyrroles and π-expanded
bis(areno)-1,4-
indolo[3,2-b]indoles.[20-27]
Recently, the technological relevance of pyrrolo[3,2-b]pyrrole derivatives has
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been demonstrated in applications such as the halocarbon detection
cartridges[28] and the organic resistive memory.[29] However, in the field of
photoelectronics, the pyrrolo[3,2-b]pyrrole derivatives are not yet studied, but
similar heteropentalenes such as thieno[3,2-b]thiophenes appear as dyes in
dye-sensitized solar cells (DSSC),[30, 31] as hole transporters in Perovskite solar
cells (PSC),[32] in organic light emitting diodes (OLED),[33] organic light emitting
transistors (OLET),[34] organic phototransistors (OPT)[35] and organic
photovoltaic cells (OPV).[36]
Pyrrolo[3,2-b]pyrrole derivatives can be synthesized via Knoevenagel
reaction between pyrrolo-2-carboxialdehydes and ethyl azidoacetate, with a
subsequent thermal cyclization.[37] Mukai and coworkers described the
preparation of these materials in multiple steps, but showed low yields.[38-40]
A
new method for their preparation was reported in 2013, consisting of a domino
reaction between an amine, an aldehyde and butane-2,3-dione in a 2:2:1
proportion and in glacial acetic acid at reflux. This reaction produces the
desired tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole derivatives; however, low
yields were still obtained (5-34%).[41] A relevant improvement in this method
was reported by the same research group in 2014, adding 10 mol% of p-toluene
sulfonic acid as a catalyst to the reaction, which led to yields between 22 and
49%.[42]
Janiga and coworkers suggest that the synthesis of tetraaryl-1,4-
dihydropyrrolo[3,2-b]pyrrole derivatives occurs by a Mannich multicomponent
reaction (MCR), with in situ generation of a Schiff base, which suffers the attack
of the enol form of the butane-2,3-dione, followed by a cyclization reaction to
3

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form an enamine intermediate. This enamine reacts with a second Schiff base,
followed by another cyclization and finally an oxidation (Scheme 1).[41]
H
O
O
H
H
O
O
H
NH2
N
H
N
H
N
H
O
O
H
N
- H2O
N
N
HO
O
O
OH
OH
N
N
- H+
HN
O
N
N
N
N
N
- H2O
[O]
N
N
Scheme 1. Mechanistic proposal for the synthesis of tetraaryl-1,4-
dihydropyrrolo[3,2-b]pyrrole derivatives.
Based on such mechanistic proposal, it is possible to point out niobium
pentachloride (NbCl5) as a promising candidate to promote the involved
pentacomponent reactions. As a matter of fact, niobium pentachloride was the
only Lewis acid capable of promoting the Mannich MCR between aniline,
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benzaldehyde and the acetophenone derivatives at room temperature with
great yields and good reaction times highlighting its powerful catalytic
properties.[43]
NbCl5 is highly electrophilic and therefore can act as a Lewis acid,
catalyzing several organic reactions and leading to excellent yields.[44-51] In
particular, good results have been obtained by using this material as catalyst in
several MCRs.[52-61] In this context, in the present report, we evaluate the use of
NbCl5 as catalyst in the synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole
derivatives by the pentacomponent reaction involving benzaldehyde, aniline and
β-diketone derivatives. Preliminary photophysical characterization of the
obtained products was also conducted. Electronic structure calculations were
carried out in order to interpret the results and also to propose derivatives with
optimized opto-electronic properties.
2.0 Experimental
2.1 materials and measurements
All reactions were performed using anhydrous Acetonitrile. All of the
chemicals were purchased from Sigma-Aldrich Chemical Co. (St. Louis, MO,
USA) and used without further purification. Thin-layer chromatography was
performed on 0.2 mm Merck 60 F254 silica gel aluminum sheets, which were
visualized
with
a
phosphomolybdic
acid/ammonium
cerium(IV)
sulfate/water/sulfuric acid mixture. Bruker DRX 400 spectrometer was used for
the NMR spectra (CDCl3 solutions) using tetramethylsilane as internal reference
1
for H and CDCl3 as an internal reference for 13C. A Jasco FTIR model 4600
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was used to record IR spectra (KBr pellets). HRMS analyses were recorded on
micrOTOF (Bruker), with ESI-TOF detector operating on positive mode. UV-Vis
spectra were recorded in an Agilent Technologies Cary 8454 and fluorescence
spectra in a SpectraMax M2, from Molecular Devices, both in room temperature
with a 10 mm quartz cuvette. Fluorescence emission spectra were obtained
using a Synergy2 Multi-Mode reader (BioTek, USA).
Quantum yields were analyzed by adjusting the solution absorption using
the UV-Vis to ca. 0.05 at 272 – 388 nm wavelength, the output was measured
using the luminescence spectrophotometer at the same wavelength and
comparing it to the known 9,10-diphenylanthracene standard using eq. 1:
ꢋ
ꢅ
ꢊ
Φꢀ
=
Φ
ꢁꢂꢃꢄ ꢅꢉ ꢉ ꢄ ꢊ
(1)
ꢆꢇꢈ
ꢋ
ꢆꢇꢈ
ꢆꢇꢈ
Φ is the fluorescence quantum yield, A is the absorption of the excitation
wavelength, F is the area under the emission curve, and n is the refractive index
of the solvents used. Subscript std denotes the standard. The compounds were
solubilized in ethanol and the concentration maintained at about 1,0x10-5 M to
follow the protocol for analysis.
2.2 Computational details
All the structures were optimized in a DFT approach employing B3LYP
(Becke, three parameter, Lee-Yang-Parr) exchange-correlation functional and
6-311G(d,p) basis set. The presence of the solvent (CH3CN) was simulated via
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polarizable continuum model (PCM) implemented in the Gaussian 09
computational package.[62]
2.3 Synthesis
2.3.1 General Procedure for the synthesis of tetraaryl-1,4-
dihydropyrrolo[3,2-b]pyrrole derivatives:
For a solution of niobium pentachloride (0.250 mmol) in 1.0 mL of
anhydrous acetonitrile, maintained at room temperature in a capped flask, we
added a solution of the benzaldehyde derivative (1a-j) (2.0 mmol), aniline
derivative (2a-e) (2.0 mmol) and β-diketone (3a-c) (1.0 mmol) in 5.0 mL of
anhydrous acetonitrile. After the addition was completed, stirring was continued
at room temperature until the end of the reaction. The reaction mixture was
quenched with water (3.0 mL). The mixture was extracted with dichloromethane
(10.0 mL). The organic layer was separated and washed with saturated sodium
bicarbonate solution (3 x 10.0 mL), saturated brine (2 x 10.0 mL), and then
dried over anhydrous magnesium sulfate. The solvent was removed under
vacuum and the resulting mixture was dissolved in boiling ethyl acetate (1.0 mL)
that, upon cooling, resulted in a red to yellow solid. This solid was recrystallized
in ethyl acetate to obtain a yellow to off-white solid, depending on the product.
1,2,4,5-Tetra-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole (4aaa): RMN-1H (400
MHz, CDCl3): δ(ppm) 7.19-7.16 (m, 8H), 7.11 (d, J=8.1 Hz, 4 H), 7.03 (d, J=8.3
Hz, 4H), 6.33 (s, 2H), 2.36 (s, 6H), 2.30 (s, 6H). RMN-13C (100 MHz, CDCl3):
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δ(ppm) 137.7 (2C), 135.7 (2C), 135.6 (2C), 135.1 (2C), 131.3 (2C), 131.0 (2C),
129.6 (4CH), 128.8 (4CH), 128.1 (4CH), 125.1 (4CH), 94.1 (2CH), 21.1 (2CH3),
21.0 (2CH3). IR (νmax/cm−1): 1734, 1610, 1513, 1475, 1373, 1135, 816. ESI-
HRMS: m/z calcd for C34H30N2 [M]+: 466.24090; found 466.2401.
2,5-Diphenyl-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole (4baa): RMN-
1H (400 MHz, CDCl3): δ(ppm) 7.22 (d, J=4.5 Hz, 10H), 7.16 (d, J=3.3 Hz, 8H),
6.38 (s, 2H), 2.37 (s, 6H). RMN-13C (100 MHz, CDCl3): δ(ppm) 137.6 (2C),
135.7 (2C), 135.3 (2C), 133.8(2C), 131.6 (2C), 129.7 (4CH), 128.2 (4CH), 128.1
(4CH), 126.0 (2CH), 125.1 (4CH), 94.5 (2CH), 21.0 (2CH3). IR (νmax/cm−1):
1596, 1515, 1470, 1383, 1141, 826. ESI-HRMS: m/z calcd for C32H26N2 [M]+:
438.20960; found 438.1365.
2,5-Bis-(4-methoxy-phenyl)-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4caa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.16-7.13 (m, 12H), 6.77 (d, J=8.8
Hz, 4H), 6.29 (s, 2H), 3.78, (s, 6H), 2.36 (s, 6H). RMN-13C (100 MHz, CDCl3):
δ(ppm) 158.1 (2C), 137.7 (2C), 135.2 (2C), 135.1 (2C), 130.9 (2C), 129.6
(4CH), 129.5 (4CH), 126.7 (2C), 125.0 (4CH), 113.6 (4CH), 93.7 (2CH), 55.2
(2CH3), 21.0 (2CH3). IR (νmax/cm−1): 1607, 1554, 1478, 1322, 1176, 1053, 798.
ESI-HRMS: m/z calcd for C34H30N2O2 [M]+: 498.23073; found 498.1479.
2,5-Bis-(4-chloro-phenyl)-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4daa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.19-7.12 (m, 16H), 6.35 (s, 2H),
2.38 (s, 6H). RMN-13C (100 MHz, CDCl3): δ(ppm) 137.2 (2C), 135.8 (2C), 134.8
(2C), 132.2 (2C), 131.9 (2C), 131.8 (2C), 129.9 (4CH), 129.2 (4CH), 128.4
(4CH), 125.1 (4CH), 94.6 (2CH), 21.0 (2CH3). IR (νmax/cm−1): 1513, 1466,
1410, 1374, 1089, 828, 546, 505. ESI-HRMS: m/z calcd for C32H24Cl2N2 [M]+:
506.13165; found 506.1319.
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2,5-Bis-(4-bromo-phenyl)-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4eaa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.33 (d, J=8.3 Hz, 4H), 7.19-7.13
(m, 8H), 7.07 (d, J=8.6 Hz, 4H), 6.35 (s, 2H), 2.38 (s, 6H). RMN-13C (100 MHz,
CDCl3): δ(ppm) 137.2 (2C), 135.8 (2C), 134.8 (2C), 132.6 (2C), 132.0 (2C),
131.3 (4CH), 129.9 (4CH), 129.5 (4CH), 125.1 (4CH), 120.0 (2C), 94.6 (2CH),
21.0 (2CH3). IR (νmax/cm−1): 1513, 1466, 1372, 1135, 1009, 819, 539. ESI-
HRMS: m/z calcd for C32H24Br2N2 [M]+: 594.03062; found 594.0309.
2,5-Bis-(4-tert-butyl-phenyl)-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4faa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.23 (d, J=8.6 Hz, 4H), 7.19 (d,
J=8.6 Hz, 4H), 7.15 (d, J=2.3 Hz, 4H), 7.13 (d, J=2.0 Hz, 4H), 6.34 (s, 2H), 2.38
(s, 6H), 1.29 (s, 9H). IR (νmax/cm−1): 2960, 1607, 1513, 1461, 1413, 1362, 1267,
1142, 829, 762. ESI-HRMS: m/z calcd for C40H42N2 [M]+: 550.33480; found
550.3344.
2,5-Bis-(4-methylsulfanyl-phenyl)-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-
b]pyrrole (4gaa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.15-7.09 (m, 16H), 6.34
(s, 2H), 2.46 (s, 6H), 2.37 (s, 6H). RMN-13C (100 MHz, CDCl3): δ(ppm) 137.5
(2C), 135.9 (2C), 135.4 (2C), 135.3 (2C), 131.7 (2C), 130.7 (2C), 129.8 (4CH),
128.4 (4CH), 126.3 (4CH), 125.1 (4CH), 94.2 (2CH), 21.0 (2CH3), 15.9 (2CH3).
IR (νmax/cm−1): 1512, 1466, 1410, 1373, 1139, 1097, 822, 753. ESI-HRMS: m/z
calcd for C34H30N2S2 [M]+: 530.18504; found 530.1954.
2,5-Bis-biphenyl-4-yl-1,4-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4haa): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.59 (d, J=8.3 Hz, 5H), 7.48 (d,
J=8.3 Hz, 5H), 7.33-7.29 (m, 8H), 7.24 (d, J=8.3 Hz, 4H), 7.19 (d, J=8.6 Hz,
4H), 6.44 (s, 2H), 2.39 (s, 6H). IR (νmax/cm−1): 1604, 1514, 1470, 1378, 1140,
843, 756. ESI-HRMS: m/z calcd for C44H34N2 [M]+: 590.27220; found 590.2719.
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1,4-Bis-(4-bromo-phenyl)-2,5-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4aba): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.46 (d, J=8.9 Hz, 4H), 7.14 (d,
J=8.6 Hz, 4H), 7.08 (q, J1=8.4 Hz, J2=5.6 Hz, 8H), 6.34 (s, 2H), 2.33 (s, 6H).
RMN-13C (100 MHz, CDCl3): δ(ppm) 139.1 (2C), 136.3 (2C), 135.8 (2C), 132.2
(4CH), 131.0 (2C), 130.4 (2C), 129.1 (4CH), 128.2 (4CH), 126.6 (4CH), 118.9
(2C), 94.9 (2CH), 21.2 (2CH3). IR (νmax/cm−1): 1586, 1530, 1489, 1401, 1373,
1134, 1072, 1008, 825, 765, 476. ESI-HRMS: m/z calcd for C32H24Br2N2 [M]+:
594.03062; found 594.0303.
1,4-Bis-(4-methoxy-phenyl)-2,5-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole
(4aca): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.21 (d, J=8.8 Hz, 4H), 7.10 (d,
J=8.3 Hz, 4H), 7.02 (d, J=8.3 Hz, 4H), 6.88 (d, J=8.8 Hz, 4H), 6.30 (s, 2H), 3.82
(s, 6H), 2.30 (s, 2H). RMN-13C (100 MHz, CDCl3): δ(ppm) 157.4 (2C), 135.8
(2C), 135.6 (2C), 133.4 (2C), 131.5 (2C), 131.0 (2C), 128.9 (4CH), 128.0 (4CH),
126.6 (4CH), 114.3 (4CH), 93.5 (2CH), 55.4 (2CH3), 21.1 (2CH3). IR
(νmax/cm−1): 1514, 1442, 1294, 1246, 1028, 822, 752. ESI-HRMS: m/z calcd for
C34H30N2O2 [M]+: 498,23073; found 498.2311.
2,5-Bis-(4-fluoro-phenyl)-1,4-bis-(4-methoxy-phenyl)-1,4-dihydro-
pyrrolo[3,2-b]pyrrole (4ica): RMN-1H (400 MHz, CDCl3): δ(ppm) 7.20-7.15 (m,
8H), 6.94-6.88 (m, 8H), 6.29 (s, 2H), 3.83 (s, 6H). RMN-13C (100 MHz, CDCl3):
δ(ppm) 162.7 (2C), 160.2 (2C), 157.7 (2C), 134.9 (2C), 133.0 (2C), 131.4 (2C),
129.8 (2CH), 129.7 (2CH), 126.6 (4CH), 115.2 (2CH), 115.0 (2CH), 114.4
(4CH), 93.6 (2CH), 55.5 (2CH3). IR (νmax/cm−1): 1514, 1460, 1296, 1250, 1213,
1032, 837, 767. ESI-HRMS: m/z calcd for C32H24F2N2O2 [M]+: 506.18058; found
506.1804.
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1,4-Diphenyl-2,5-di-p-tolyl-1,4-dihydro-pyrrolo[3,2-b]pyrrole (4ada): RMN-
1H (400 MHz, CDCl3): δ(ppm) 7.34 (d, J=7.3 Hz, 5H), 7.29 (d, J=7.3 Hz, 5H),
7.11 (d, J=8.1 Hz, 4H), 7.03 (d, J=8.1 Hz, 4H), 6.38 (s, 2H), 2.31 (s, 6H). RMN-
13C (100 MHz, CDCl3): δ(ppm) 140.2 (2C), 135.9 (2C), 135.7 (2C), 131.3 (2C),
130.9 (2C), 129.0(4CH), 128.9(4CH), 128.1 (4CH), 125.5 (2CH), 125.2 (4CH),
94.6 (2CH), 21.1 (2CH3). IR (νmax/cm−1): 1595, 1498, 1433, 1371, 1130, 816,
751, 694. ESI-HRMS: m/z calcd for C32H26N2 [M]+: 438.20960; found 438.2095.
Methyl
4-{2,4,5-tris[4-(methoxycarbonyl)phenyl]pyrrolo[3,2-b]pyrrol-1-
yl}benzoate (4jea): RMN-1H (400 MHz, CDCl3): δ(ppm) 8.06 (d, J=8.8 Hz, 4H),
7.91 (d, J=8.6 Hz, 4H), 7.32 (d, J=8.6 Hz, 4H), 7.27 (d, J=8.6 Hz, 4H), 6.56 (s,
2H), 3.94 (s, 6H), 3.90 (s, 6H). RMN-13C (100 MHz, CDCl3): δ(ppm) 166.8 (2C),
166.3 (2C), 143.4 (2C), 137.3 (2C), 135.8 (2C), 132.5 (2C), 130.9 (4CH), 129.7
(4CH), 128.0 (2C), 127.7 (4CH), 124.6 (4CH), 97.3 (2CH), 52.2 (2CH3), 52.1
(2CH3). IR (νmax/cm−1): 1727, 1685, 1577, 1502, 1437, 1391, 1284, 1203, 1107,
1013, 851, 809, 757, 686. ESI-HRMS: m/z calcd for C38H30N2O8 [M]+:
642.20022; found 642.2007.
3.0. Results and Discussion
3.1 Synthetic studies
The optimization studies of the synthesis of tetraaryl-1,4-dihydropyrrolo-
[3,2-b]pyrrole derivatives by MCR were made using tolualdehyde (1a), toluidine
(2a) and 2,3-butanodione (3a) in different solvents and varying the proportions
of NbCl5 catalyst (Scheme 2 and Table 1). From these tests, the best conditions
11

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obtained were those using acetonitrile as solvent and the proportion of 0.250
mmol of NbCl5 as catalyst. It is interesting to note that no product formation is
observed in the acetic acid-based systems, differently from the systems
containing NbCl5. Another noteworthy result is that a high concentration of
NbCl5 (more than 0.250 mmol) does not improve the reaction yield, probably
due to the formation of by-products during the synthesis.
Scheme 2. Optimization reaction tests.
Table 1.
Optimization tests results.
Entry
Solvent
NbCl5 amount
(mmol)
0.250
Yield (%)
Reaction
time (min)
1
2
3
4
5
6
Acetic acid
Dichloromethane
Acetonitrile
-
120
50
40
20
10
10
0.250
0.125
0.250
0.500
50
70
82
82
65
Acetonitrile
Acetonitrile
Acetonitrile
1.000
Based on these results, several reactions involving different
benzaldehyde derivatives (1a-j), aniline derivatives (2a-e) and β-diketone
derivatives (3a-c) in the presence of 0.250 mmols of NbCl5 and using MeCN as
solvent were performed (see Scheme 3). The obtained results are shown in
Table 2.
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Scheme 3. MCR using aniline, benzaldehyde and β-diketone derivatives in the
presence of NbCl5, as catalyst.
Table 2.
Results of the synthesis of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives
by MRCs using NbCl5.
Reaction
Benzaldehyde
derivative
Aniline
derivative diketone
β-
Entry
Yield (%)
time
(min)
20
20
20
40
30
20
40
40
40
40
40
20
40
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1a
1b
1c
1d
1e
1f
1g
1h
1a
1a
1i
1a
1j
1i
1a
1h
1a
1i
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2c
2d
2e
2a
2a
2a
2b
2b
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3b
3b
3c
82 (4aaa)
85 (4baa)
98 (4caa)
95 (4daa)
92 (4eaa)
73 (4faa)
98 (4gaa)
83 (4haa)
80 (4aba)
77 (4aca)
59 (4ica)
68 (4ada)
96 (4jea)
--- (4iab)
--- (4aac)
--- (4hab)
--- (4abb)
--- (4ibc)
120
120
120
120
120
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Note that the substituents in para position of benzaldehyde or aniline
have small effects on the reaction yields or on their completion times. In
general, reactions employing 3b and 3c β-diketones do not lead to the
formation of the desired products. These results can be associated with sterical
hindrance in the second Schiff base attack due to the presence of alkyl groups
in 3b and 3c diketones, which prevents the formation of tetraaryl-1,4-
dihydropyrrolo-[3,2-b]pyrrole derivatives. Figure 1 illustrates the difference in the
volume of these compounds (data coming from electronic structure calculations)
reinforcing this hypothesis.
Fig 1.Total volume of 3a, 3b and 3c β-diketones.
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Comparing the results obtained in this work with others found in the
literature (Table 3), it is possible to verify the effectiveness of NbCl5 as catalyst
in the synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole derivatives.[41,42]
Table 3.
Comparison between the results presented in this report and the ones found in
the literature.
Catalyst
proportion (%)
12.5*
Product
Lewis acid
Time (min)
Yield (%)
4aaa
4aaa
4aaa
4baa
4baa
4baa
4caa
4caa
4aba
4aba
4aba
4aca
4aca
4ica
NbCl5
AcOH
TsOH
NbCl5
AcOH
TsOH
NbCl5
AcOH
NbCl5
AcOH
TsOH
NbCl5
AcOH
NbCl5
AcOH
20
210
210
20
210
210
20
210
40
210
210
40
82
34
34
85
33
34
98
15
80
15
22
77
-
Solvent
10
12.5*
Solvent
10
12.5*
Solvent
12.5*
Solvent
10
12.5*
Solvent
12.5*
210
40
210
59
07
4ica
Solvent
*0.250 mmols of NbCl5 were used, corresponding to 12.5 mol% to the aniline
derivative used.
The results show that niobium pentachloride can be considered an
efficient catalyst in comparison with other Lewis acids (regarding reaction time
and yield).
It is worth mentioning that compounds 4aca are obtained only in NbCl5
catalyzed reactions. We believe that the great oxophilicity of niobium
pentachloride explains that result, since the NbCl5 can bond to the oxygen of
15

ACCEPTED MANUSCRIPT
the methoxy group in the 4-anisaldehyde, thus stabilizing the molecule, which
does not occur in the presence of the acetic acid.
In order to better understand some essential features of the mechanisms
involved in the synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole
derivatives, the local softness of each of the 1, 2 and 3 components were
calculated. The tendency of atoms interactions was evaluated via HSAB (hard-
soft acid-base) principle.
The local softness (s+ and s–) was obtained via Condensed-to-atoms
Fukui indexes (CAFI). Despite being obtained via a very simplified approach,
these descriptors have been successfully employed to understand and predict
reactivity features of distinct molecules and polymers.[63-67] Given the nature of
the involved reactions, only CAFIs associated with nucleophilic (f+) and
electrophilic (f–) agents were calculated.
ꢎ
ꢐ
ꢒ
ꢐ ꢒ
ꢌ = ꢏꢍ ꢑ + 1 − ꢏꢍ ꢑ
(2)
(3)
ꢍ
ꢓ
ꢐ ꢒ
ꢐ
ꢒ
ꢌ = ꢏꢍ ꢑ − ꢏꢍ ꢑ − 1
ꢍ
where qi(N+1), qi(N) and qi(N−1) represent the electronic population in
the i-th atom of anionic, cationic and neutral species of the system under study,
respectively. The Hirshfeld partition method was employed to estimate the
electronic populations in order to avoid negative CAFI values.[68]
The electronic descriptors s+ and s– were obtained from the multiplication
of CAFIs with the global softness of the compounds (S=1/(IP-EA)):
ꢔꢍꢕ = ꢖ. ꢌꢕ,
fork = + or –
(4)
ꢍ
where IP and EA represent, respectively, the ionization potential and the
electron affinity of the species estimated via Eq. 5 and 6.
ꢐ
ꢒ
ꢐ ꢒ
ꢗꢘ = ꢙ ꢑ − 1 − ꢙ ꢑ ,
(5)
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ꢐ ꢒ
ꢐ
ꢒ
ꢙꢚ = ꢙ ꢑ − ꢙ ꢑ + 1 ,
(6)
with E(M) representing the total energy of the chemical species with M
electrons.
According to the HSAB principle, electrophile/nucleophile interactions are
favored when the involved atoms present similar softness.[69,70] In this sense, it
was possible to propose specific reactions occurring during the synthesis
process.
Figure 2 illustrates the local softness of i) compound 1 for reactions
toward nucleophiles (s+) and ii) compounds 2 and 3 for reactions toward
electrophiles (s–).
Fig 2. Local softness of compounds 1 (s+), 2 (s–) and 3 (s–).
As it can be noticed, the interaction between C7 of compound 1 (yellow
circle) and N7 of compound 2 (yellow square) is favored, given the major
similarity of the relative softness of these atoms. An effective interaction
17

ACCEPTED MANUSCRIPT
between these sites leads to the formation of specific intermediates, which are
necessary for the production of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole
derivatives (see Scheme 1). However, the results presented in Fig. 2 indicate
that effective interactions can also occur between C7 of compound 1 (yellow
circles) and oxygen atoms of compound 3 (cyan and yellow triangles),
suggesting a possible competing route for the formation of compounds 4 that
could explain the small yield differences presented in Table 3.
Figure 3 illustrates the correlation between ꢛꢜꢝꢞꢔꢟꢎꢠ ꢒ − ꢔꢢꢓꢐꢣ /ꢣ ꢒꢞꢥ (that is
ꢐ
ꢤ
ꢡ
ꢡ
a measure of the difference between the local softness of the C7 of compound 1
and O5, or O7, of compound 3) and the experimental yields. It is possible to
observe that a linear relation is obtained, indicating that systems with lower
probability of direct interactions between compounds 1 and 3 present higher
yields, which is compatible with the mechanism proposed in Scheme 2.
Compound 4ica was identified as a possible outlier, which can be associated
with the higher proximity between the s– indexes of N7 of compound 2c and O5
(O7) of compound 3 (in comparison with 2a, 2b, 2d and 2e).
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Fig 3. Correlation between total yields and the similarity between the local
softness of C7 of compound 1 and O5 (or O7) of compound 3.
These results suggest that there are two competing mechanisms
occurring during the synthesis process related to the interaction between C7 of
compound 1 and N7 of compound 2 (a desired route) and C7 of compound 1
and O5 (or O7) of compound 3 (undesired one). The balance between these
routes can be (at some degree) adjusted by an appropriate choice of R1 and R2
ligands (excluding steric effects). Additional linear regressions reinforce this
hypothesis (see Supplementary Information for details).
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3.2 Photophysical studies
Considering the potential applications of tetraaryl-1,4-dihydropyrrolo-[3,2-
b] pyrroles in organic electronics, a preliminary photo-physical characterization
of the obtained compounds was performed. The optical properties were
evaluated in dichloromethane and in the UV-Vis region. Figures 4 and 5, and
Table 4 present the main results obtained.
Table 4.
Summary of the main optical data of the compounds.
Compound λabs (nm) λemi (nm) Stokes shift (nm) ε (L.M-1.cm-1) Φ[a]
4aaa
4baa
4caa
4daa
4eaa
4faa
4gaa
4haa
4aba
4aca
4ica
348
349
343
360
361
351
344
382
348
346
336
349
294
418
418
418
420
420
420
434
460
460
417
415
420
430
70
69
75
60
59
69
90
78
112
71
79
71
136
1,6 x 105
3,6 x 105
2,3 x 105
4,2 x 105
5,2 x 105
3,3 x 105
4,0 x 105
4,9 x 105
3,5 x 105
4,2 x 105
3,7 x 105
2,6 x 105
4,6 x 104
0.45
0.56
0.07
0.83
0.06
0.11
0.87
0.90
0.03
0.22
0.42
0.38
0.03
4ada
4jea
Determined using 9,10-diphenylanthracene in ethanol (1,0x10-5 M) as
[a]
standard.
20

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Fig 4. UV-Vis absorption spectra of the studied compounds.
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Fig 5. Fluorescence spectra of the studied compounds.
Most of the compounds present significant absorbance between 294 and
382 nm, suggesting that these materials can be employed as sensitizing dyes in
optoelectronic devices.
In general, it is possible to observe that the presence of the chlorine,
bromine and phenyl groups in the benzaldehyde p-position leads to a
bathochromic effect in the spectra. Such red-shift can be associated with the
extension of the conjugation length promoted by the presence of the phenyl
group, as well as halogen inductive effects that stabilize the excited state. On
the other hand, a small hypsochromic shift is observed in the spectra when the
fluorine group is present in aniline, and methoxy is present in the benzaldehyde
22

ACCEPTED MANUSCRIPT
derivative. Such effect can be associated with the strong electronegative effect
induced by the fluorine atom that, in turn, destabilizes the excited state.
Regarding fluorescence, it is observed that most of the compounds
present maximum emission, about 420 nm. Compounds 4haa and 4aba
present the highest red shift, with the main emission peak close to 460 nm for
both products. In relation to the quantum yields, it is observed that compounds
4caa, 4eaa, 4aba and 4jea present very low efficiencies (?? < 0.1), while
compounds 4daa, 4gaa and 4haa present the highest values (?? > 0.8). The
low ?? values associated with compounds containing bromine atoms (4eaa and
4aba) can be associated to the heavy atom effect [71], however such effect is not
present in chlorine-containing systems (4daa).
In order to better evaluate the transitions involved, theoretical absorption
spectra were carried out for all the products obtained (compounds 4aaa–4jea
are presented in Table 3). In addition, 90 new derivatives obtained from varied
combinations of distinct R1 (H, 4-CH3, Br, Cl, 4-OCH3, 4-NO2) and R2 (H; 4-Cl;
4-Br; 4-F; 4-NO2; 4-OCH3; 4-CH3; 4-C(CH3)3; 4-N(CH3)2; 4-SCH3; 4-Ph 2,4-OH;
3-OCH3; 4-OH; 2,4,6-CH3) ligands were evaluated so as to propose compounds
with improved optoelectronic properties.
The theoretical absorption spectra of the compounds were calculated in a
time-dependent DFT (TD-DFT) approach with B3LYP functional and 6-
311G(d,p) basis set. The presence of the solvent (CH2Cl2) was simulated using
the PCM. All the calculations were performed with the aid of the Gaussian
computational package.[62]
Figure 6 illustrates the relation between experimental and predicted
optical absorption main peak position. As it can be noticed, a linear relationship
23

ACCEPTED MANUSCRIPT
is observed for most derivatives. Compound 4jea was identified as a possible
outlier. Compounds 4ica and 4gaa present not so dissonant results.
Fig 6. Relationship between theoretical and experimental optical absorption
main peak position of the compounds. The linear fit is based only on the black
points. Red points were identified as possible outliers.
The absorption spectra of the compounds are in general composed by
two or three main peaks (see Figure 4) that can be associated with π-π*
transitions (see Supplementary Information). It is noticed that the presence of
the distinct ligands changes the balance between the amplitude of these peaks.
Particularly, the spectrum of the 4jea compound does not present the transition
24

ACCEPTED MANUSCRIPT
at higher wavelengths, which can suggest possible problems in the formation of
an extended π-conjugated system during the synthesis process.
Figure 7 illustrates the most relevant Kohn-Sham orbitals involved in the
main optical transitions of the compound 4aaa. HOMO, LUMO, HOMO-n and
LUMO-m represent, respectively, the highest occupied molecular orbital, the
lowest unoccupied molecular orbital, the n-th energy level below the HOMO and
the m-th energy level above the LUMO. Very similar results were obtained for
the other 12 compounds and are presented in detail in the Supplementary
Information.
Fig 7. Relevant Kohn-Sham orbitals involved in the main optical transitions of
the compound 4aaa.
As it can be observed, the main absorption peak is associated with a
HOMO→LUMO (H-L) transition. In this context, given the HOMO distribution
and the high relative oscillator strength (fosc) of H-L transition, it is possible to
consider that the optical responses of compounds 4 are more highly regulated
by substitutions in R1 than in R2. Secondary significant transitions involving
25

ACCEPTED MANUSCRIPT
HOMO-1→LUMO (H1-L) and HOMO→LUMO+4 (H-L4) are also observed,
which in some cases involve orbitals located at the aniline-based ring (R2 ring).
However, the associated fosc values are quite small for these transitions,
indicating that they have no significant effect on the overall spectra.
Despite of being very difficult to interpret the varied factors that can
influence the photoluminescence of the compounds in solution, the analysis of
Figure 7 and Figures S2-S13 (see Supplementary Information) suggest that the
obtained quantum yields depends on the spatial distribution of the LUMO on the
structure of the compounds. In general it is observed that compounds with low
quantum yields present a significant part of the LUMO located on the R2 rings.
This feature are more evident in the compounds with very low quantum yields,
as 4caa, 4aba and 4jea (with an exception to compound 4eaa in which heavy
atom effect apparently dominates the optical response) and it is absent in
compounds with the highest yields (4daa, 4gaa and 4haa) and could be
associated with non-radiative routes. However, more studies are still necessary
for an in deep analysis, which are not in the scope of the present work.
Aiming at better evaluating the influence of the ligands on the optical
properties of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrroles, the optical absorption
spectra of 90 distinct derivatives were (only theoretically) assessed. These
compounds were designed considering typical substitutions that could be
promoted in R1 and R2 positions (R1 = H, 4-CH3, Br, Cl, 4-OCH3, 4-NO2 / R2 =
H; 4-Cl; 4-Br; 4-F; 4-NO2; 4-OCH3; 4-CH3; 4-C(CH3)3; 4-N(CH3)2; 4-SCH3; 4-Ph
2,4-OH; 3-OCH3; 4-OH; 2,4,6-CH3). Figure 8 illustrates the influence of each
ligand, R1 and R2, on the main peak position of the derivatives (details regarding
26

ACCEPTED MANUSCRIPT
the optical properties of these compounds can be found in the Supplementary
Information).
Fig 8. Influence of the R1 (a) and R2 (b) substituents on the main peak position
of the tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives absorption spectra.
The results reinforce our previous considerations, indicating that the main
optical properties of the derivatives are indeed related to the R1 substituent. In
particular, absorptions in the range of 500-600 nm are observed for R1=NO2,
while absorptions at lower wavelengths are observed for R1=H and 4-CH3. Very
weak dependence on the nature of R2 substituent is observed. In general,
absorptions at lower wavelengths are obtained for R2=4-Ph, while R2=NO2
leads to absorptions at higher wavelengths than when R1=OCH3.
These results suggest that compounds with improved optical properties
can be obtained via an appropriate choice of R1 substituents. Additional
statistical studies are currently underway in order to propose and test guided
routes for the production of materials with improved optoelectronic properties.
4.0 Conclusions
27

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The objective of the present study was to show a new methodology for
the synthesis of tetraaryl-1,4-dihydropyrrolo[3,2-b]pyrrole derivatives by a
multicomponent reaction between benzaldehyde, aniline and butane-2,3-dione
derivatives, promoted by niobium pentachloride. Excellent yields and low
reaction times were obtained under mild conditions. Electronic structure
calculations indicate the existence of competing mechanisms occurring during
the synthesis process that can be modulated, in some degree, by an
appropriate choice of the benzaldehyde and aniline derivatives.
The optical characterization of the obtained tetraaryl-1,4-dihydropyrrolo-
[3,2-b]pyrrole derivatives point out that such compounds can be employed as
sensitizer dyes in organic electronic devices.[8,72] By means of theoretical
studies, it was possible to assess relevant information on the optical properties
of these materials. Above all, it was possible to identify that the main features of
the absorption spectra of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives
are controlled by the nature of the benzaldehyde derivatives employed in the
MCR process.
Acknowledgements
The authors would like to acknowledge the Fundação de Amparo à
Pesquisa do Estado de São Paulo (FAPESP) (Proc. 16/01599-1), Conselho
Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Proc.
302753/2015-0, Proc. 448310/2014-7), Coordenadoria de Aperfeiçoamento de
Pessoal do Nível Superior (CAPES) and Pró-Reitoria de Pesquisa da UNESP
(PROPe-UNESP, PROPe-UNESP-PIBIC-Reitoria-Proj. 40037) for their financial
28

ACCEPTED MANUSCRIPT
support. The authors would also like to thank the Companhia Brasileira de
Metalurgia e Mineração (CBMM) for supplying the niobium pentachloride. This
research was also supported by resources provided by the Center for Scientific
Computing (NCC/GridUNESP) of São Paulo State University (UNESP).
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