Synthesis of 2-arylpyrroles via catalytic dehydrogenation of 2-aryl-1-pyrrolines in the presence of palladium-supported on alumina

Article abstract of DOI:10.1016/j.tet.2015.04.043

A convenient synthesis of 2-arylpyrroles from the catalytic dehydrogenation of 2-aryl-1-pyrrolines in the presence of commercial palladium-supported on alumina (Pd/Al₂O₃) is described. The reaction scope was tested for aryl substituents with different steric hindrances and electronic natures. The dehydrogenation reaction conditions such as temperature, reflux time and amount of catalyst, revealed to be highly dependent on the 2-aryl substituent group, moderate to high yields and selectivities being obtained in a reaction involving straightforward work-up and purification procedures. In addition, the synthesis of the corresponding 2-aryl-1-pyrroline starting materials, through the cyclisation reaction involving 4-chlorobutyronitrile and aryl Grignard reagents, is also reported.

Full text of DOI:10.1016/j.tet.2015.04.043

Accepted Manuscript
Synthesis of 2-arylpyrroles via catalytic dehydrogenation of 2-aryl-1-pyrrolines in the
presence of palladium-supported on alumina
Cláudia A. Figueira, Patrícia S. Lopes, Pedro T. Gomes
PII:
S0040-4020(15)00542-6
10.1016/j.tet.2015.04.043
TET 26646
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 16 March 2015
Revised Date: 13 April 2015
Accepted Date: 16 April 2015
Please cite this article as: Figueira CA, Lopes PS, Gomes PT, Synthesis of 2-arylpyrroles via catalytic
dehydrogenation of 2-aryl-1-pyrrolines in the presence of palladium-supported on alumina, Tetrahedron
(2015), doi: 10.1016/j.tet.2015.04.043.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Synthesis of 2-arylpyrroles via catalytic dehydrogenation of 2-aryl-1-pyrrolines in the
presence of palladium-supported on alumina
Cláudia A. Figueira, Patrícia S. Lopes and Pedro T. Gomes*
Centro de Química Estrutural, Departamento de Engenharia Química, Instituto Superior Técnico, Av.
Rovisco Pais, 1049-001 Lisboa, Portugal
Different 2-aryl-1-pyrrolines, obtained by cyclisation reaction of 4-chlorobutyronitrile with
aryl Grignard reagents, were dehydrogenated in the presence of a commercial palladium-
supported on alumina catalyst (Pd/Al2O3), giving rise to the corresponding 2-arylpyrroles in
moderate to high yields and selectivities.

ACCEPTED MANUSCRIPT
Synthesis of 2-arylpyrroles via catalytic dehydrogenation of
2-aryl-1-pyrrolines in the presence of palladium-supported
on alumina
Cláudia A. Figueira, Patrícia S. Lopes and Pedro T. Gomes*
Centro de Química Estrutural, Departamento de Engenharia Química, Instituto Superior
Técnico, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
Phone: (+351) 218419612; Fax: (+351) 218417246
E-mail: pedro.t.gomes@tecnico.ulisboa.pt
Abstract: A convenient synthesis of 2-arylpyrroles from the catalytic dehydrogenation of 2-
aryl-1-pyrrolines in the presence of commercial palladium-supported on alumina (Pd/Al2O3)
is described. The reaction scope was tested for aryl substituents with different steric
hindrances and electronic natures. The dehydrogenation reaction conditions such as
temperature, reflux time and amount of catalyst, revealed to be highly dependent on the 2-aryl
substituent group, moderate to high yields and selectivities being obtained in a reaction
involving straightforward work-up and purification procedures. In addition, the synthesis of
the corresponding 2-aryl-1-pyrroline starting materials, through the cyclisation reaction
involving 4-chlorobutyronitrile and aryl Grignard reagents, is also reported.
Keywords: dehydrogenation; heterogeneous catalysis; nitrogen heterocycles; palladium
2

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1. Introduction
Pyrrole and their substituted derivatives are highly important and versatile N-heterocyclic
molecules. They are present in many natural products with biological properties, are
important intermediates in supramolecular chemistry (for the synthesis of porphyrins and
porphyrinoids) and can be applied in a diversity of areas such as ligands for coordination
chemistry, electrically conducting materials, optical sensors or light-emitting devices.1
In particular, the 2-arylpyrrole derivatives, in addition to their presence in natural
products and characteristic biological activity,2 are components of pharmaceutical and
medicinal agents,3 finding also applications in the synthesis of organogels,4 dyes,5 and
pesticides.6 Several methods to synthesise 2-arylpyrroles have been developed, the formers
including addition reactions followed by cyclisation7 or [3+2] cycloadditions,8 intramolecular
cyclisations,9 ring modifications (such as contraction or expansion),10 the most recent ones
employing visible-light and transition-metal photocatalysis.11 However, in a number of
examples, the 2-phenylpyrrole is the only product reported, owing to the very specific nature
of the starting materials employed. Additionally, some of those synthetic pathways are also
time-consuming and/or lead to low yields in the desired products.
Metal-catalysed cross-coupling reactions revealed to be an efficient method to introduce
aryl substituents in the C2 position of NH-pyrroles. Negishi coupling type reactions with in
situ generated pyrrol-1-ylzinc halides,12 Stille reactions with pyrrolyl tin compounds,13 or
Suzuki coupling reactions involving 2-bromopyrrole or 2-pyrroleboronic acid3c-e,5a-b were
some of the examples reported. Moderate to high yields are obtained, requiring though
homogeneous phosphine-palladium catalysts (e.g. [PdCl2(PPh3)2] or [Pd(PPh3)4]), their cost
and the need of separation from the reaction medium being possible disadvantages.
Additionally, these methods require activated and/or protected pyrroles, implying extra
reaction steps, and the reported yields are very often not reproducible when scaling-up these
reactions beyond the one millimole scale
.
The direct arylation of N-methyl pyrrole derivatives has been reported in the literature by
efficient methods, namely that described by Doucet and co-workers using very low loadings
of [Pd(OAc)2].2a,14 However, the direct C2 arylation of the NH-pyrrole has shown to be a
more challenging route to achieve 2-arylpyrroles. Some examples were reported, which
employed phosphine-free palladium catalysts, such as [Pd(OH)2/C],3g [Pd(OAc)2]15 or
[Pd(η3C3H5)Cl]2.16 Catalysts bearing other metals were also used, such as in situ formed aryl-
rhodium(III) complexes,17 iridium catalytic systems derived from the commercially available
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Crabtree’s catalyst,18 and also iron19 and cobalt20 based catalysts. Nevertheless, some of the
drawbacks mentioned for the metal-catalysed cross-coupling reactions are also observed.
The dehydrogenation reactions of the corresponding heterocyclic rings, total or partially
saturated, have been also considered as efficient processes to obtain pyrroles. In fact, several
heterogeneous palladium catalysts were patented for the dehydrogenation reaction of the NH-
pyrrolidine or pyrrolidines aliphatically substituted in any position of the heterocycle.21 In
addition, and in particular, 2-arylpyrroles were obtained from the corresponding 2-
arylpyrrolidines when a heterogeneous nickel catalyst22 or molecular sulphur23 were
employed. Activated carbon per se also revealed to be an efficient dehydrogenating agent.
Experiments with 2-phenyl-1-pyrroline24 and similar heterocycles (imidazolines,25 1,2,3,4-
tetrahydroquinolines or 1,2,3,4-tetrahydrocarbazoles26) yielded the corresponding
heteroaromatic compounds, although high amounts of activated carbon were required, the
process not being considered as catalytic. Good results were also obtained for the latter
substrates when palladium and activated carbon were combined in the form of a [Pd/C]
catalyst.26
In a preliminary communication, we reported the dehydrogenation reaction of the 2-
phenyl-1-pyrroline to 2-phenylpyrrole employing catalytic amounts of palladium-supported
on activated carbon, [Pd/C], or on alumina, [Pd/Al2O3].27 In the present work, we extend the
use of the latter catalyst to the synthesis of 2-arylpyrroles with different electronic and steric
natures, leading to reactions characterised by high yields and selectivities, and avoiding
difficult purification procedures. This work describes also the synthesis of the 2-aryl-1-
pyrroline starting materials obtained by cyclization reaction between the corresponding Grignard
reagents (aryl)MgBr and 4-chlorobutyronitrile.
2. Results and Discussion
The different 2-aryl-1-pyrroline starting materials were synthesised according to a
methodology adapted from literature.24,27,28 It consisted in the reaction of 4-
chlorobutyronitrile with different in situ prepared aryl Grignard reagents to generate the
corresponding intermediate addition products, which, upon ring cyclisation, gave rise to the
target 2-aryl-1-pyrrolines 1a-g (Table 1) in moderate yields.
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Table 1. Reaction of aryl Grignard reagents (in situ prepared) with 4-chlorobutyronitrile to give
the 2-aryl-1-pyrrolines 1a-g.
Aryl bromide
reagent
2-aryl-1-pyrroline
product
Yield
(%)
47
1a
51
1b
1c
47
20
1d
1e
59
52
54
1f
1g
Conditions: 1) Aryl bromide; Mg (excess); Solvent: diethyl
ether; T = 40 ºC, t = 2 h (24 h for 1e); 2) 4-chlorobutyronitrile
(equimolar); Solvent: diethyl ether; T = 40 ºC, t = 1.5 h (21 h
for 1e) and then solvent exchange to xylene; T = 110 ºC, t = 1
– 3 h (depending on the type and amount of substrate;
overnight for 1e).
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Whenever bulky substituents were present in the adjacent positions of the reactive aryl
bromide carbon (such as in compounds 1c-e), longer reaction times were required for the
syntheses of the respective Grignard reagents and 2-aryl-1-pyrrolines. Although the synthesis
of 2-mesityl-1-pyrroline and 2-anthracen-9-yl-1-pyrroline (1e) were already described using
1
13
this same procedure (though lower yields were obtained and no H and C NMR data were
disclosed),29 this is the first time that the 2-aryl-1-pyrrolines 1c and 1d are reported. It is
noteworthy that the other methods described in the literature for the synthesis of 2-aryl-1-
pyrrolines30 do not report pyrrolines containing bulky 2,6-substituted phenyl substituents.
The presence of electron-withdrawing substituents on the aryl ring led to different results.
For instance, when para-fluorophenyl bromide reagent was used, the expected product 1g was
obtained in moderate yields, but attempts to synthesise the 2-(3,5-ditrifluoromethylphenyl)-1-
pyrroline or the 2-pentafluorophenyl-1-pyrroline revealed to be unsuccessful.
The catalytic dehydrogenation of the 2-aryl-1-pyrrolines to the corresponding 2-
arylpyrroles herein reported had its origin in previous works about the aromatisation of 2-
phenyl-1-pyrroline to 2-phenylpyrrole, initially applying activated carbon only as
dehydrogenation agent,24 and more recently using different palladium-supported catalysts,
[10%-Pd/C] and [10%-Pd/Al2O3].27 The reaction usually presented a high selectivity in the
desired product but, when activated carbon was employed alone, very high amounts were
required, the process being considered as catalytic only when palladium was also used.
In the present work, the 2-aryl-1-pyrrolines (1a-g) were dissolved in the appropriate
solvent and the commercial catalyst [10%-Pd/Al2O3] suspended, the mixture being refluxed
under nitrogen until maximum conversion (Table 2).
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Table 2. Reaction data of the catalytic dehydrogenation of the 2-aryl-1-pyrrolines 1a-g to the
corresponding 2-arylpyrroles 2a-g in the presence of [10%-Pd/Al2O3]: conversions in 2-aryl-1-
pyrrolines, yields in 2-arylpyrroles, selectivities in 2-arylpyrroles, and catalyst activities.
TOF g
(min-1)
b
2-aryl-1-pyrroline 2-arylpyrrole
reagent product
n0,pyrroline
(mmol)
Pd c
Time Conv. d Yield e
(%) (%)
Select. f
(%)
(mol%) (h)
153.9
26.6
0.4
0.4
1.5
98
90 (79)
93 i
2.778
1.534
1a
2a
2.7
91
99
90
79 (68)
90 (66)
80 j
2b
2c
1b
1c
50.2
9.9
10.0
10.0
100
100
0.002
0.001
136
46
98
78
98 (53)
1d
1e
2d
2e
6.4
10.0
55 (28) h
70 k
0.003
13.0
13.0
0.4
2.0
3
97
89
83 (69)
89 (78)
86 l
1.347
0.008
1f
2f
92
100
1g
2g
a Conditions for a, b, f and g: Solvent: xylene; T = 150 ºC. Conditions for c-e: Solvent: 1,2,4-trichlorobenzene (TCB); T = 230 ºC. b n0,pyrroline
= initial moles of 2-aryl-1-pyrroline 1a-g. c mol% Pd = [nPd/n0,pyrroline]×100; nPd = moles of Pd in catalyst [10%-Pd/Al2O3]. d Conversion (%) of
e
2-aryl-1-pyrrolines 1a-g = 100×(npyrrole+nby-product)/n0,pyrroline; determined by 1H NMR spectroscopy. Yield (%) in 2-arylpyrroles 2a-g =
100×npyrrole/n0,pyrroline; determined by 1H NMR at the end of reaction; between parentheses, yield of isolated product after work-up (see text).
f
1
g
Selectivity (%) in 2-arylpyrroles 2a-g = 100×npyrrole/(npyrrole+nby-product); determined by H NMR. TOF = turnover frequency = (npyrrole+nby-
product)/(nPd×time). h Low yield after work-up due to a difficult purification. i By-product = 4-phenylbutan-1-amine (3a) (see Scheme 1). j By-
k
l
product = N-propyl-(3,5-dimethylphenyl)-1-formimine (3b) (see Scheme 2).
methoxyphenyl)butan-1-amine (3f) (see Scheme 1).
By-product = anthracene.
By-product = 4-(4-

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In the previous study of the catalytic dehydrogenation of 2-phenyl-1-pyrroline 1a to 2-
phenylpyrrole 2a,27 we concluded that the best experimental conditions were the use of 0.4
mol% Pd of the [10%-Pd/Al2O3] catalyst in relation to the substrate and 1.5‒2 h of reaction
time. Herein, we attempted the synthesis of other 2-arylpyrroles using the same optimised
conditions, the reaction of 1a to 2a being also reported in Table 2 for comparison. For the 2-
aryl-1-pyrrolines 1b and 1f, containing electron-releasing substituents at the meta- or para-
positions of the aryl ring, the optimal conditions employed for 1a were applicable and the
results obtained were similar (see Table 2 and Figure 1).
Figure 1. Yield in 2-arylpyrroles 2a, 2b and 2f versus reaction time for the catalytic dehydrogenation
of the corresponding 2-aryl-1-pyrrolines (1a, 1b and 1f).
For the 2-aryl-1-pyrrolines containing electron-withdrawing substituents on the aryl ring (1g),
bulky substituents at the ortho-positions of the aryl ring (1c,d) or sterically hindered aryl rings
(1e), the reaction conditions had to be adjusted in order to obtain the corresponding pyrrole
products. In the first case, an amount of catalyst five times higher was required and the
reaction time had to be extended for ca. 4 days, in order to attain high yields in the desired
product. Conversely, in the remaining cases, significant increases in the amount of catalyst,
reaction time and temperature (10% of Pd and 230 ºC, using 1,2,4-trichlorobenzene (TCB) as
solvent) were required (see Table 2 and Figure 2), reflecting the higher steric constraints of
these bulky pyrrolines.

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Figure 2. Yield in 2-arylpyrroles 2c-e and 2g versus reaction time for the catalytic dehydrogenation of
the corresponding 2-aryl-1-pyrrolines (1c-e and 1g).
For the pyrrolines containing unhindered and donor 2-aryl substituents (such as 1a, 1b and
1f), it was observed that, along with the dehydrogenation reaction leading to 2a, 2b or 2f,
respectively, the heterocyclic ring also undergoes a reductive ring-opening transformation
giving rise to a single by-product in each of the reactions, respectively 3a, 3b and 3f
(Schemes 1 and 2), which were identified by 1H NMR spectroscopy (see Figures S15-S17 in
Supplementary Material). The formation of by-products 3a, 3b and 3f possibly occurs by a
Pd-catalysed hydrogenolysis (making use of the molecular H2 formed), leading however to
different ring-opening regioselectivities of the pyrroline rings. For 1a and 1f, 4-arylbutan-1-
amines are formed, whereas an N-propyl(arylformimine) by-product arises for the case of the
meta-disubstituted 2-aryl-1-pyrroline 1b. Nevertheless, these reactions have selectivities over
80% on the dehydrogenation products, the formed by-products being easily separated from
the desired 2-arylpyrroles by a simple washing with n-hexane (for 2a,b,g) or other solvents
(CH2Cl2/n-hexane (1:4) for 2c, and diethyl ether for 2f). Although very convenient, this
simple and fast purification procedure leads to considerable losses in the isolated products,
giving lower final yields (values between parentheses in column 7 of Table 2), owing to
partial dissolution of the 2-arylpyrroles in these solvents.
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Scheme 1. Formation of amines 3a and 3f as by-products of the dehydrogenation reactions of 1a and
1f, by reductive ring-opening of the pyrroline N-heterocycle.
Scheme 2. Formation of N-propyl-(3,5-dimethylphenyl)-1-formimine as by-product of the
dehydrogenation reaction of 1b, by reductive ring-opening of the pyrroline N-heterocycle.
For the case of 1g, despite its low bulkiness, the presence of the electron-withdrawing fluorine
atom inhibited this type of reaction and no by-products were observed. Similarly, for the case
pyrrolines substituted with bulky 2,6-dialkylaryl rings (1c and 1d), the heterocycle
unsaturated bond is protected, no side-reactions being observed. Nevertheless, for 1e, the
harsher reaction conditions required for the dehydrogenation also induced the decomposition
of the substrate, free anthracene being detected in the reaction medium (and separated by
column chromatography), thus decreasing the selectivity in 2e.
Crystals suitable for single-crystal X-ray diffraction were obtained for compounds 1c,d
and 2c-f. Their molecular structures are represented respectively in Figures 3 and 4 and the
corresponding selected bond distances and angles are listed in Tables S1 and S2 in the
Supplementary Data. The molecular structure of 1a was previously reported by us, as the first
example of a totally planar monosubstituted 1-pyrroline.31 Unlike 1a, compound 1c (Figure
3a) presents not only a considerably less planar heterocycle (with deviation of ca. 0.089 Å for
atoms C4 and C5), but also a totally different conformation between both rings, now
perpendicular with a dihedral angle of 89.2(2)º, owing to the presence of the two ortho-
methyl substituents. In compound 1d (Figure 3b), the heterocyclic ring has a more
pronounced distortion due to the presence of the bulky ortho-isopropyl substituents on the
phenyl ring, with deviations from planarity between 0.128 and 0.157 Å for atoms C3-5, but
showing a smaller dihedral angle of 69.75(10)º with the aryl ring.
10

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Figure 3. ORTEP III diagram top (left) and side (right) views of 2-aryl-1-pyrrolines (a) 1c and (b) 1d.
Hydrogen atoms were omitted for clarity.
The molecular structures of the 2-arylpyrroles 2c-f exhibit similar characteristics, the main
difference being related once again to the influence of the aryl ring on the conformation
between the aryl and pyrrole moieties (Figure 4). In the case of 2c (Figure 4a), which contains
two independent molecules, A and B, the dihedral angles between the aryl and pyrrole rings
are nearly perpendicular (88.42(10)º and 85.28(10)º, respectively), due to the presence of the
methyl groups in positions 2 and 6 of the phenyl ring. Similarly, the isopropyl groups in
positions 2 and 6 of the phenyl ring of 2d (Figure 4b) also induces a high dihedral angle of
80.60(17)º. The anthracen-9-yl ring in 2e (Figure 4c) gives rise to a less sterically crowded
neighbourhood and a lower dihedral angle is observed (63.30(11)º), whereas 2f (Figure 4d) is
characterised by a quasi-planar geometry, with a dihedral angle of 12.2(3)º.
11

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Figure 4. ORTEP III diagram top (left) and side (right) views of 2-arylpyrroles (a) 2c, (b) 2d, (c) 2e
and (d) 2f. Hydrogen atoms, with exception of the NH, were omitted for clarity.
As expected, the molecular structures of pyrrolines 1c,d are quite similar to those of the
corresponding pyrroles 2c,d. The main difference is associated with the pyrroline
aromatisation in the latter compounds, the N-heterocycles becoming now fully planar rings
(atom deviations below 0.002 Å) with concomitant contraction of all ring bonds. In the case
of the bulky 2,4,6-triisopropylphenyl substituent, its conformation in relation to the
heterocycle moiety was also influenced by the aromatisation, the highest difference in the
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dihedral angles of the pyrroline and its corresponding pyrrole being observed (69.75(10)º vs.
80.60(17)º).
The differences observed in the experimental conditions required to achieve the
maximum reaction conversion (i.e. the different activation energies) are connected with the
structural features of reagents and products presented above. Because these reactions are
performed under heterogeneous catalytic conditions, the hydrogen abstraction by the catalyst
occurs when the pyrroline ring approaches the catalyst active sites on the support surface. For
instance, the 2-aryl-1-pyrrolines 1a,b,f can be envisaged to sit on the surface of the catalyst in
a planar fashion, its structure being more favourable towards dehydrogenation due to an
efficient interaction with the Pd atoms of the surface active sites. Conversely, the bulkiness of
the ortho-substituents in the aryl ring of pyrrolines 1c-e imposes a perpendicular
conformation and harsher reaction conditions are required for that interaction.
We believe that a mechanism similar to that proposed for the dehydrogenation of the 2-
phenyl-1-pyrroline27 may be also operating for the present 2-aryl-1-pyrrolines (Scheme 3).
Reagents 1 and the active Pd sites (S) of the catalyst surface are involved in a pre-equilibrium,
generating adsorbed pyrroline (1S), which undergoes irreversible dehydrogenation to give the
main products 2 and releasing an equivalent of molecular H2. The H2 formed plays different
roles: on the one hand, it can be involved in an adsorption equilibrium with the surface Pd
sites, dissociating to form palladium hydride species and, on the other hand, it can participate
in a reductive ring-opening reaction of the heterocyclic rings, originating by-products (3a,b,f)
via a Pd-catalysed hydrogenolysis.
Scheme 3. Proposed mechanism for the dehydrogenation reaction of 2-aryl-1-pyrrolines (1) to the
corresponding 2-arylpyrroles (2) in the presence of the Pd/Al2O3 catalyst.
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3. Conclusions
A new method is described for the preparation of 2-arylpyrroles via the catalytic
dehydrogenation reaction of the corresponding 2-aryl-1-pyrrolines (obtained by the
cyclisation reaction of 4-chlorobutyronitrile with aryl Grignard reagents, also described in the
present work), employing a commercial Pd/Al2O3 heterogeneous catalyst. The reaction
conditions (temperature, time and amount of catalyst), required to achieve efficient
dehydrogenations, were dependent upon the electronic and steric nature of the 2-aryl
substituents used. Optimization of the reaction conditions led to moderate to high yields in the
desired products after a simple work-up, with exception of 2-(anthracen-9-yl)pyrrole 2e,
which requires purification by column chromatography.
4. Experimental
4.1. General information
All reagents were acquired from commercial suppliers and used without further purification.
Heterogeneous catalyst [10%-Pd/Al2O3] (Fluka) was used without any additional treatment. All
solvents were pre-dried with 4 Å molecular sieves and purified by refluxing over a suitable drying
agent followed by distillation under nitrogen. Diethyl ether, toluene and xylene were dried over
sodium/benzophenone and n-hexane over calcium hydride. Deuterated chloroform was dried with 4 Å
molecular sieves. Compounds 1e and 2e were purified by column chromatography using silica gel 60
A (0.035-0.070 mm). Purification was monitored by thin layer chromatography (TLC) using silica gel
60 ADAMANTTM on TLC plates with fluorescent indicator 254 nm. Nuclear Magnetic Resonance
(NMR) spectra were recorded on Bruker Avance III 300 (1H, 300.130 MHz; 13C, 75.468 MHz; 19F,
282.404 MHz) or Bruker Avance III 400 (1H, 400.130 MHz; 13C, 100.613 MHz) spectrometers.
Spectra were referenced internally using the residual protio-solvent (1H) or solvent (13C) resonances
relative to tetramethylsilane (δ=0), or externally using the CFCl3 (19F) resonance (δ=0). All resonances
were characterised by its chemical shifts (δ), quoted in ppm, and coupling constants (J), given in Hz.
Multiplicities were abbreviated as follows: broad (br), singlet (s), doublet (d), doublet of doublets (dd),
triplet (t), quintet (quin), heptet (hept) and multiplet (m). Elemental analyses were performed in a
Fisons Instrument Mod EA-1108, at Laboratório de Análises (IST).
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4.2. General procedure for the synthesis of 2-aryl-1-pyrrolines
This procedure was adapted from the literature.28 Unless stated otherwise, the Grignard reagent was
prepared by adding dropwise the corresponding aryl bromide to a suspension of excess of magnesium
turnings and a few iodine crystals in diethyl ether. The solution was kept for 2 h at 40 ºC. The heating
was turned off and a solution of an equimolar amount of 4-chlorobutyronitrile in diethyl ether was
added dropwise to the in situ prepared Grignard reagent. The reaction mixture was refluxed for 1.5 h
and the temperature was then increased up to 110 ºC to distil off the diethyl ether while xylene was
added to keep the total volume constant. The mixture was allowed to cool to room temperature, and a
saturated aqueous solution of NH4Cl was added, which caused phases separation. The aqueous phase
was repeatedly washed with diethyl ether and the combined organic phases were acidified with a 10%
HCl aqueous solution. After extraction, the aqueous acidic solution was neutralised with a NaOH 1M
aqueous solution, in an ice bath. Diethyl ether was added and the organic layer extracted and washed
with distilled water. After drying over anhydrous MgSO4, the diethyl ether was removed under
vacuum and the remaining product purified by trap-to-trap distillation, column chromatography or
recrystallization in the appropriate solvent.
4.2.1. 2-phenyl-1-pyrroline (1a). The phenyl Grignard reagent was prepared from bromobenzene (39.5
mL, 375 mmol) and magnesium turnings (9.24 g, 380 mmol) in diethyl ether (250 mL). Addition of a
solution of 4-chlorobutyronitrile (23.2 mL, 375 mmol) in diethyl ether (250 mL) and subsequent
reaction afforded a dark-brown oil, which was purified by trap-to-trap distillation (80 ºC and 10-1
mbar). The resulting light yellow oil was stored at 4 ºC, yielding 25.8 g (47%) of 1a as colourless
crystals. 1H NMR (300 MHz, CDCl3): δ = 7.83-7.80 (m, 2H, Ph-Hortho), 7.38-7.35 (m, Ph-Hmeta and Ph-
Hpara), 4.09-4.03 (m, 2H, H5 pyrr), 2.97-2.90 (m, 2H, H3 pyrr), 2.08-1.96 (m, 2H, H4 pyrr) ppm.
4.2.2. 2-(3,5-dimethylphenyl)-1-pyrroline (1b). The 3,5-dimethylphenyl Grignard reagent was
prepared from 1-bromo-3,5-dimethylbenzene (7.1 mL, 53 mmol) and magnesium turnings (1.34 g, 55
mmol) in diethyl ether (35 mL). Addition of a solution of 4-chlorobutyronitrile (5.0 mL, 53 mmol) in
diethyl ether (25 mL) and subsequent reaction afforded an orange oil, which was purified by trap-to-
trap distillation (75 ºC and 7×10-3 mbar). The resulting colourless oil was stored at -20 ºC, yielding
1
4.75 g (51%) of 1b as microcrystalline aggregate crystals. H NMR (300 MHz, CDCl3):
δ = 7.44 (s,
3
3
2H, Ph-Hortho), 7.02 (s, 1H, Ph-Hpara), 4.01 (t, JHH = 7.3 Hz, 2H, H5 pyrr), 2.88 (t, JHH = 8.1 Hz, 2H,
H3 pyrr), 2.32 (s, 6H, CH3), 2.02-1.92 (m, 2H, H4 pyrr) ppm. 13C NMR (75 MHz, CDCl3):
= 173.5
δ
(C2 pyrr), 137.8 (Ph-Cmeta), 134.4 (Ph-Cipso), 131.9 (Ph-Cpara), 125.3 (Ph-Cortho), 61.3 (C5 pyrr), 34.8
(C3 pyrr), 22.6 (C4 pyrr), 21.1 (CH3) ppm. Anal. Calcd. for C12H15N: C 83.19; H 8.73; N 8.08. Found:
C 83.58; H 7.87; N 8.16.
15

ACCEPTED MANUSCRIPT
4.2.3. 2-(2,6-dimethylphenyl)-1-pyrroline (1c). The 2,6-dimethylphenyl Grignard reagent was prepared
from 1-bromo-2,6-dimethylbenzene (30.0 mL, 225 mmol) and magnesium turnings (5.59 g, 230
mmol) in diethyl ether (140 mL). Addition of a solution of 4-chlorobutyronitrile (21.6 mL, 225 mmol)
in diethyl ether (100 mL) and subsequent reaction afforded a yellow oil, which was purified by trap-
to-trap distillation (70 ºC and 8×10-3 mbar). The resulting product was isolated as a white crystalline
solid that was recrystallised in diethyl ether at -20 ºC, yielding 18.24 g (47%) of 1c as colourless
crystals. 1H NMR (300 MHz, CDCl3):
Hmeta), 4.10-4.05 (m, 2H, H5 pyrr), 2.74-2.67 (m, 2H, H3 pyrr), 2.21 (s, 6H, CH3), 2.10-1.99 (m, 2H,
H4 pyrr) ppm. 13C NMR (75 MHz, CDCl3):
= 176.8 (C2 pyrr), 137.0 (Ph-Cipso), 134.9 (Ph-Cortho),
δ
= 7.16-7.11 (m, 1H, Ph-Hpara), 7.03 (d, 3JHH = 7.6 Hz, 2H, Ph-
δ
127.9 (Ph-Cpara), 127.5 (Ph-Cmeta), 61.8 (C5 pyrr), 39.4 (C3 pyrr), 23.1 (C4 pyrr), 19.5 (CH3) ppm.
Anal. Calcd. for C12H15N: C 83.19; H 8.73; N 8.08. Found: C 83.05; H 8.79; N 8.06.
4.2.4. 2-(2,4,6-triisopropylphenyl)-1-pyrroline (1d). The 2,4,6-triisopropylphenyl Grignard reagent
was prepared from 1-bromo-2,4,6-triisoproylbenzene (8.9 mL, 35 mmol) and magnesium turnings
(1.72 g, 71 mmol) in diethyl ether (50 mL). Addition of a solution of 4-chlorobutyronitrile (3.4 mL, 35
mmol) in diethyl ether (50 mL) and subsequent reaction afforded a brown oil, which was purified by
trap-to-trap distillation (90 ºC and 10-1 mbar). The resulting product was isolated as a white yellowish
solid that was recrystallised in n-hexane at -20 ºC, yielding 1.88 g (20%) of 1d as colourless crystals.
3
1H NMR (300 MHz, CDCl3):
δ
= 6.99 (s, 2H, Ph-Hmeta), 4.07 (t, JHH = 7.1 Hz, 2H, H5 pyrr), 2.89
3
(hept, JHH = 6.9 Hz, 1H, para-CH(CH3)2), 2.75-2.67 (m, 4H, ortho-CH(CH3)2 and H3 pyrr), 2.03
(quin, 3JHH = 6.0 Hz, 2H, H4 pyrr), 1.25 (d, 3JHH = 6.0 Hz, 6H, para-CH(CH3)2), 1.21 (d, 3JHH = 6.0 Hz,
12H, ortho-CH(CH3)2) ppm. 13C NMR (75 MHz, CDCl3):
δ = 176.7 (C2 pyrr), 148.8 (Ph-Cipso), 145.6
(Ph-Cortho), 132.3 (Ph-Cpara), 120.9 (Ph-Cmeta), 61.9 (C5 pyrr), 41.9 (C3 pyrr), 34.4 (para-CH(CH3)2),
30.9 (ortho-CH(CH3)2), 24.6 (para-CH(CH3)2), 24.2 (ortho-CH(CH3)2), 23.2 (C4 pyrr) ppm. Anal.
Calcd. for C19H29N: C 84.07; H 10.77; N 5.16. Found: C 83.83; H 10.77; N 5.07.
4.2.5. 2-(anthracen-9-yl)-1-pyrroline (1e). Due to the nature of the brominated reagent, the anthracen-
9-yl Grignard reagent was prepared by adding magnesium wire (0.378 g, 15.76 mmol) to a solution of
9-bromoanthracene (2.0 g, 7.78 mmol) in diethyl ether (25 mL). A few drops of ethyl bromide were
added instead the iodine crystals and the Grignard reaction was maintained over 24 h. After addition
of the solution of 4-chlorobutyronitrile (0.75 mL, 7.78 mmol) in diethyl ether (30 mL), the reaction
was kept for an additional period of 21 h. After solvent exchange to xylene, the final reaction mixture
was kept overnight at 145 ºC. The dark-yellow oily-gel product formed was purified by column
chromatography with a mixture of ethyl acetate:n-hexane (1:1) as eluent. Removal of all volatiles
1
yielded 0.291 g (59%) of 1e as an orange solid. H NMR (400 MHz, CDCl3):
δ
= 8.45 (s, 1H, H13),
3
8.04-8.01 (m, 2H, H8), 7.86-7.84 (m, 2H, H11), 7.48-7.46 (m, 4H, H9 and H10), 4.39 (t, JHH = 7.0
16

ACCEPTED MANUSCRIPT
3
Hz, 2H, H5 pyrr), 3.03 (t, JHH = 8.0 Hz, 2H, H3 pyrr), 2.33-2.26 (m, 2H, H4 pyrr) ppm. 13C NMR
(101 MHz, CDCl3): = 176.0 (C2 pyrr), 131.9 (Cipso), 131.4 (C7 and C12), 128.8 (C8), 127.5 (C13),
δ
126.2 (C9), 125.4 (C10), 125.3 (C11), 62.7 (C5 pyrr), 41.9 (C3 pyrr), 23.5 (C4 pyrr) ppm. Anal.
Calcd. for C18H15N: C 88.13; H 6.16; N 5.71. Found: C 88.25; H 6.17; N 5.70.
4.2.6. 2-(4-methoxyphenyl)-1-pyrroline (1f). The 4-methoxyphenyl Grignard reagent was prepared
from 1-bromo-4-methoxybenzene (6.3 mL, 50 mmol) and magnesium turnings (1.96 g, 81 mmol) in
diethyl ether (35 mL). Addition of a solution of 4-chlorobutyronitrile (4.8 mL, 50 mmol) in diethyl
ether (25 mL) and subsequent reaction afforded a light yellow oil, which was purified by trap-to-trap
distillation (60 ºC and 7×10-3 mbar). The resulting product was isolated as a white crystalline solid that
1
was recrystallised in diethyl ether at -20 ºC, yielding 4.52 g (52%) of 1f as colourless crystals. H
3
3
NMR (400 MHz, CDCl3):
δ
= 7.79 (d, JHH = 8.8 Hz, 2H, Ph-Hortho), 6.91 (d, JHH = 8.8 Hz, 2H, Ph-
3
3
Hmeta), 4.03 (t, JHH = 7.3 Hz, 2H, H5 pyrr), 3.84 (s, 3H, CH3), 2.91 (t, JHH = 8.2 Hz, 2H, H3 pyrr),
2.06-1.98 (m, 2H, H4 pyrr) ppm. 13C NMR (101 MHz, CDCl3):
δ = 172.7 (C2 pyrr), 161.4 (Ph-Cpara),
129.3 (Ph-Cortho), 127.7 (Ph-Cipso), 113.9 (Ph-Cmeta), 61.5 (C5 pyrr), 55.5 (CH3), 35.0 (C3 pyrr), 22.9
(C4 pyrr) ppm. Anal. Calcd. for C11H13NO: C 75.40; H 7.48; N 7.99. Found: C 75.24; H 8.03; N 8.00.
4.2.7. 2-(4-fluorophenyl)-1-pyrroline (1g). The 4-fluorophenyl Grignard reagent was prepared from 1-
bromo-4-fluorobenzene (5.5 mL, 50 mmol) and magnesium turnings (1.34 g, 55 mmol) in diethyl
ether (35 mL). Addition of a solution of 4-chlorobutyronitrile (4.8 mL, 50 mmol) in diethyl ether (25
mL) and subsequent reaction afforded a red brownish solid, which was subsequently extracted with n-
hexane. Concentration to 1/3 of the solution at -20 ºC yielded 4.38 g (54%) of 1g as a light yellow
crystalline solid. 1H NMR (300 MHz, CDCl3):
Hortho), 7.08 (t, 3JHH = 8.7 Hz, 2H, Ph-Hmeta), 4.05 (t, 3JHH = 7.3 Hz, 2H, H5 pyrr), 2.92 (t, 3JHH = 8.2 Hz,
2H, H3 pyrr), 2.04 (m, 2H, H4 pyrr) ppm. 13C NMR (75 MHz, CDCl3):
= 172.2 (C2 pyrr), 164.2 (d,
1JCF = 250.2 Hz, Ph-Cpara), 131.1 (Ph-Cipso), 129.7 (d, 3JCF = 8.5 Hz, Ph-Cortho), 115.5 (d, 2JCF = 21.7 Hz,
Ph-Cmeta), 61.7 (C5 pyrr), 35.1 (C3 pyrr), 22.9 (C4 pyrr) ppm. 19F{1H} NMR (282 MHz, CDCl3):
= -
δ
= 7.85-7.81 (dd, 3JHH = 8.7 Hz, 4JHF = 5.6 Hz, 2H, Ph-
δ
δ
110.38 ppm. Anal. Calcd. for C10H10FN: C 73.60; H 6.18; N 8.58. Found: C 73.22; H 6.28; N 8.52.
4.3. General procedure for the synthesis of 2-arylpyrroles
A solution of the corresponding 2-aryl-1-pyrroline was prepared in an appropriate solvent (xylene or
1,2,4-trichlorobenzene (TCB)). The [10%-Pd/Al2O3] catalyst was added and the mixture refluxed
under nitrogen (at 150 or 230 ºC, respectively for xylene or TCB solvents). The conversion was
1
monitored by H NMR by collecting aliquots of the reaction medium. After reaching the maximum
conversion, the reflux was stopped. The reaction medium was allowed to cool, the mixture filtered and
17

ACCEPTED MANUSCRIPT
the remaining catalyst further extracted with fresh xylene. The solvent was removed under vacuum
and the solid washed with cold n-hexane.
4.3.1. 2-phenylpyrrole (2a). A solution of 1a (22.35 g, 153.9 mmol) in xylene (80 mL) was refluxed in
the presence of [10%-Pd/Al2O3] (0.660 g, 0.62 mmol Pd) for 2 h, at 150 ºC, affording 17.44 g (79%)
1
of 2a as a white solid. H NMR (300 MHz, CDCl3):
δ = 8.44 (br, s, 1H, NH), 7.50-7.47 (m, 2H, Ph-
Hortho), 7.40-7.34 (m, 2H, Ph-Hmeta), 7.24-7.18 (m, 1H, Ph-Hpara), 6.88-6.86 (m, 1H, H5 pyrr), 6.55-
6.52 (m, 1H, H3 pyrr), 6.32-6.29 (m, 1H, H4 pyrr) ppm. Anal. Calcd. for C10H9N: C 83.88; H 6.34; N
9.78. Found: C 83.48; H 6.45; N 9.70.
4.3.2. 2-(3,5-dimethylphenyl)pyrrole (2b). A solution of 1b (4.60 g, 26.6 mmol) in xylene (50 mL) was
refluxed in the presence of [10%-Pd/Al2O3] (0.113 g, 0.106 mmol Pd) for 2.5 h, at 150 ºC, affording
3.08 g (68%) of 2b as a white solid. 1H NMR (300 MHz, CDCl3):
Ph-Hortho), 6.88 (s, 1H, Ph-Hpara), 6.85-6.83 (m, 1H, H5 pyrr), 6.53-6.51 (m, 1H, H3 pyrr), 6.32-6.29
(m, 1H, H4 pyrr), 2.36 (s, 6H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
= 138.5 (Ph-Cmeta), 132.8
δ = 8.40 (br, 1H, NH), 7.12 (s, 2H,
δ
(Ph-Cipso), 132.5 (C2), 128.1 (Ph-Cpara), 122.0 (Ph-Cortho), 118.6 (C5 pyrr), 110.1 (C4 pyrr), 105.9 (C3
pyrr), 21.5 (CH3) ppm. Anal. Calcd. for C12H13N: C 84.17; H 7.65; N 8.18. Found: C 83.80; H 7.81; N
8.16.
4.3.3. 2-(2,6-dimethylphenyl)pyrrole (2c). A solution of 1c (8.69 g, 50.2 mmol) in 1,2,4-TCB (30 mL)
was refluxed in the presence of [10%-Pd/Al2O3] (5.47 g, 5.01 mmol Pd) for 91 h, at 230 ºC. The crude
product was solubilised in CH2Cl2, the solution was concentrated and n-hexane (1:4) was added with
stirring at -20 ºC. Filtration and removal of the volatiles gave 5.65 g (66%) of 2c as a crystalline brown
solid. Colourless crystals of product were obtained together with the crude during the evaporation of
1,2,4-TCB, which were characterised by X-ray diffraction. 1H NMR (300 MHz, CDCl3):
δ = 7.91 (br,
3
1H, NH), 7.19-7.16 (m, 1H, Ph-Hpara), 7.11 (d, JHH = 7.4 Hz, 2H, Ph-Hmeta), 6.86 (br, 1H, H5 pyrr),
6.34-6.31 (m, 1H, H3 pyrr), 6.09 (br, 1H, H4 pyrr), 2.17 (s, 6H, CH3) ppm. 13C NMR (75 MHz,
CDCl3):
δ = 138.8 (Ph-Cortho), 133.8 (Ph-Cipso), 129.6 (C2 pyrr), 128.01 (Ph-Cpara), 127.4 (Ph-Cmeta),
117.1 (C5 pyrr), 108.7 (C4 pyrr), 108.3 (C3 pyrr), 20.8 (CH3) ppm. Anal. Calcd. for C12H13N: C 84.17;
H 7.65; N 8.18. Found: C 83.83; H 7.60; N 8.20.
4.3.4. 2-(2,4,6-triisopropylphenyl)pyrrole (2d). A solution of 1d (2.68 g, 9.9 mmol) in 1,2,4-TCB (50
mL) was refluxed in the presence of [10%-Pd/Al2O3] (1.052 g, 0.989 mmol Pd) for 136 h, at 230 ºC.
Due to its high solubility, the crude product was extracted with n-hexane at room temperature and
stored at -20 ºC, yielding 1.42 g (53%) of 2d as a crystalline brown solid. White crystals of product
were obtained together with the crude during the evaporation of 1,2,4-TCB, which were characterised
18

ACCEPTED MANUSCRIPT
by X-ray diffraction. 1H NMR (400 MHz, CDCl3):
δ = 7.95 (br, 1H, NH), 7.08 (s, 2H, Ph-Hmeta), 6.85
3
(br, 1H, H5 pyrr), 6.33-6.31 (m, 1H, H3 pyrr), 6.10 (br, 1H, H4 pyrr), 2.96 (hept, JHH = 6.8 Hz, 1H,
3
3
para-CH(CH3)2), 2.74 (hept, JHH = 6.9 Hz, 2H, ortho-CH(CH3)2), 1.32 (d, JHH = 6.0 Hz, 6H, para-
3
CH(CH3)2), 1.15 (d, JHH = 6.0 Hz, 12H, ortho-CH(CH3)2) ppm. 13C NMR (101 MHz, CDCl3):
δ =
149.8 (Ph-Cpara), 149.3 (Ph-Cortho), 129.2 (C2 pyrr), 128.9 (Ph-Cipso), 120.7 (Ph-Cmeta), 116.7 (C5 pyrr),
109.1 (C3 pyrr), 108.4 (C4 pyrr), 34.5 (para-CH(CH3)2), 30.7 (ortho-CH(CH3)2), 24.7 (para-
CH(CH3)2), 24.2 (ortho-CH(CH3)2) ppm. Anal. Calcd. for C19H27N: C 84.70; H 10.10; N 5.20. Found:
C 84.30; H 10.00; N 5.06.
4.3.5. 2-(anthracen-9-yl)pyrrole (2e). A solution of 1e (1.58 g, 6.4 mmol) in 1,2,4-TCB (30 mL) was
refluxed in the presence of [10%-Pd/Al2O3] (0.685 g, 0.644 mmol Pd) for 46 h, at 230 ºC. The crude
was purified by column chromatography with n-hexane:ethyl acetate (3:1) as eluent, two fractions
being obtained, which were evaporated to dryness. The first fraction corresponded to anthracene and
the second one was constituted by pure 2e. The latter product was further solubilised in n-hexane at
-20 ºC, filtered and 0.436 g (28%) of 2e were obtained as an orange solid after solvent evaporation and
drying under vacuum. Slow solvent evaporation at room temperature also afforded red crystals
1
suitable for X-ray diffraction. H NMR (400 MHz, CDCl3):
δ = 8.48 (s, 1H, H13), 8.31 (br, 1H, NH),
3
3
8.03 (d, JHH = 8.4 Hz, 2H, H8), 7.93 (d, JHH = 8.7 Hz, 2H, H11), 7.49-7.39 (m, 4H, H9 and H10),
7.07 (br, 1H, H5 pyrr), 6.55-6.53 (m, 1H, H3 pyrr), 6.51 (br, 1H, H4 pyrr) ppm. 13C NMR (101 MHz,
CDCl3):
δ = 131.9 (C12), 131.5 (C7), 128.7 (Cipso), 128.5 (C8), 127.5 (C13), 127.4 (C2 pyrr), 126.8
(C11), 125.9 (C10), 125.4 (C9), 118.2 (C5 pyrr), 111.5 (C4 pyrr), 109.1 (C3 pyrr) ppm. Anal. Calcd.
for C18H13N: C 88.86; H 5.39; N 5.76. Found: C 89.13; H 5.55; N 5.59.
4.3.6. 2-(4-methoxyphenyl)pyrrole (2f). A solution of 1f (2.28 g, 13.0 mmol) in xylene (30 mL) was
refluxed in the presence of [10%-Pd/Al2O3] (0.055 g, 0.052 mmol Pd) for 3 h, at 150 ºC. The solution
was filtered still hot and the residue washed with cold diethyl ether, affording 1.55 g (69%) of 2f as a
white crystalline solid. Recrystallization in diethyl ether at room temperature also gave colourless
1
crystals suitable for X-ray diffraction. H NMR (400 MHz, CDCl3):
δ = 8.34 (br, 1H, NH), 7.41 (d,
3
3JHH = 8.7 Hz, 2H, Ph-Hortho), 6.92 (d, JHH = 8.6 Hz, 2H, Ph-Hmeta), 6.83 (br, 1H, H5 pyrr), 6.42 (br,
13
1H, H3 pyrr), 6.30-6.28 (m, 1H, H4 pyrr), 3.83 (s, 3H, CH3) ppm. C NMR (101 MHz, CDCl3):
δ =
158.4 (Ph-Cpara), 132.3 (C2 pyrr), 126.1 (Ph-Cipso), 125.4 (Ph-Cortho), 118.3 (C5 pyrr), 114.5 (Ph-Cmeta),
110.1 (C4 pyrr), 105.0 (C3 pyrr), 55.5 (CH3) ppm. Anal. Calcd. for C11H11NO: C 76.28; H 6.40; N
8.09. Found: C 76.27; H 6.47; N 8.11.
4.3.7. 2-(4-fluorophenyl)pyrrole (2g). A solution of 1g (2.12 g, 13.0 mmol) in xylene (30 mL) was
refluxed in the presence of [10%-Pd/Al2O3] (0.277 g, 0.26 mmol Pd) for 92 h, at 150 ºC, affording
19

ACCEPTED MANUSCRIPT
δ
1.63 g (78%) of 2g as a white solid. 1H NMR (400 MHz, CDCl3): = 8.34 (br, 1H, NH), 7.43 (dd, 3JHH
4
3
= 8.6 Hz, JHF = 5.3 Hz, 2H, Ph-Hortho), 7.07 (t, JHH = 8.6 Hz, 2H, Ph-Hmeta), 6.86 (br, 1H, H5 pyrr),
13
6.46 (br, 1H, H3 pyrr), 6.31-6.29 (m, 1H, H4 pyrr) ppm. C NMR (101 MHz, CDCl3):
δ = 161.6 (d,
1JCF = 245.5 Hz, Ph-Cpara), 131.5 (C2 pyrr), 129.3 (d, 4JCF = 3.2 Hz, Ph-Cipso), 125.7 (d, 3JCF = 7.9 Hz,
Ph-Cortho), 119.0 (C5 pyrr), 116.0 (d, 2JCF = 21.7 Hz, Ph-Cmeta), 110.3 (C4 pyrr), 106.0 (C3 pyrr) ppm.
19F{1H} NMR (282 MHz, CDCl3): δ = -116.30 ppm. Anal. Calcd. for C10H8FN: C 74.52; H 5.00; N
8.69. Found: C 75.00; H 5.07; N 8.63.
4.4. Crystallographic data
Crystallographic and experimental details of crystal structure determinations are listed in Tables S3
and S4 in the Supporting Information. Crystals of compounds 1c,d and 2c-f were covered with
polyfluoroether oil and mounted on a nylon loop. Crystallographic data were collected using graphite
monochromated Mo-Kα radiation (λ=0.71073Å) on a Bruker AXS-KAPPA APEX II diffractometer
equipped with an Oxford Cryosystem open-flow nitrogen cryostat, at 150 K. Cell parameters were
retrieved using Bruker SMART software and refined using Bruker SAINT on all observed reflections.
Absorption corrections were applied using SADABS.32 Structure solution and refinement were
performed using direct methods with the programs SIR92,33 or SIR2004,34 both included in the
software package WinGX-Version 2013.335 and SHELXL-2013.36 All non-hydrogen atoms were
refined anisotropically and the hydrogen atoms, except the NH protons, were inserted in idealised
positions and allowed to refine riding on the parent carbon atom. The NH protons were located in the
electron density map. DFIX restraints were made in the NH bonds for compounds 2e and 2f.
Additionaly, the crystals of 2f were of poor quality, though the structure refined to a perfect
convergence. Figures of the molecular structures were generated using ORTEP-337 software available
at the Cambridge Crystallographic Data Centre (CCDC). The data were deposited in CCDC under the
deposit numbers 1043390 for 1c, 1043391 for 1d, 1043392 for 2c, 1043393 for 2d, 1043394 for 2e
and 1043395 for 2f. CCDC-1043390 to 1043395 contain the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
The authors thank the Fundação para a Ciência e Tecnologia for financial support (Projects
PTDC/EQU-EQU/110313/2009, UID/QUI/00100/2013 and RECI/QEQ-QIN70189/2012) and
for fellowships to C.A.F. (SFRH/BD/47730/2008) and P.S.L. (SFRH/BD/88639/2012).
20

ACCEPTED MANUSCRIPT
Supplementary data
1
13
1
Copies of H and C NMR spectra for all products, H NMR spectra for the reactions with
formation of by-products (3a, 3b and 3f), and crystallographic data for 2-aryl-1-pyrrolines
(1c,d) and for 2-arylpyrroles (2c-f) are available in supplementary data. Supplementary data
associated with this article can be found in the online version, at
http://dx.doi.org/10.1016/j.tet.2015. … .
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Supplementary Material for
Synthesis of 2-arylpyrroles via catalytic dehydrogenation of
2-aryl-1-pyrrolines in the presence of palladium-supported on alumina
Cláudia A. Figueira, Patrícia S. Lopes and Pedro T. Gomes*
Centro de Química Estrutural, Departamento de Engenharia Química, Instituto Superior Técnico,
Universidade de Lisboa, Av. Rovisco Pais, 1049-001 Lisboa, Portugal
* Corresponding Author; e-mail: pedro.t.gomes@tecnico.ulisboa.pt

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Contents
Page
S3
NMR spectra for the 2-aryl-1-pyrrolines and 2-arylpyrroles synthesised
NMR spectra for the reactions with formation of by-products (3a, 3b and 3f)
Crystallographic data for 2-aryl-1-pyrrolines (1c,d) and for 2-arylpyrroles (2c-f)
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NMR spectra of the 2-aryl-1-pyrrolines and 2-arylpyrroles synthesised
Figure S1 1H NMR (CDCl3, 300 MHz) spectrum of 2-phenyl-1-pyrroline (1a).
Figure S2a 1H NMR (CDCl3, 300 MHz) spectrum of 2-(3,5-dimethylphenyl)-1-pyrroline (1b).
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Figure S2b 13C{1H} NMR (CDCl3, 75 MHz) spectrum of 2-(3,5-dimethylphenyl)-1-pyrroline (1b).
Figure S3a 1H NMR (CDCl3, 300 MHz) spectrum of 2-(2,6-dimethylphenyl)-1-pyrroline (1c).
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Figure S3b 13C{1H} NMR (CDCl3, 75 MHz) spectrum of 2-(2,6-dimethylphenyl)-1-pyrroline (1c).
Figure S4a 1H NMR (CDCl3, 300 MHz) spectrum of 2-(2,4,6-triisopropylphenyl)-1-pyrroline (1d).
S5