A Synthetic Methodology for Pyrroles from Nitrodienes

Article abstract of DOI:10.1002/ejoc.201701814

Palladium complexes containing the ligand 4,7-dimethoxy-1,10-phenanthroline have been used to catalyze the reductive cyclization of nitrodienes using carbon monoxide as the reductant to give pyrroles. Carbon dioxide was the only stoichiometric byproduct of the reaction. The yields were good and the starting materials can be easily synthesized in two steps by a cross-aldol condensation reaction followed by a Henry reaction. Different substitution patterns are tolerated by this novel synthetic strategy.

Full text of DOI:10.1002/ejoc.201701814

A Journal of
Accepted Article
Title: A novel synthetic methodology for pyrroles from nitrodienes
Authors: Mohamed A. EL-Atawy, Francesco Ferretti, and Fabio
Ragaini
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201701814
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10.1002/ejoc.201701814
European Journal of Organic Chemistry
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A novel synthetic methodology for pyrroles from nitrodienes
Mohamed A. EL-Atawy,[a,b] Francesco Ferretti,[a] and Fabio Ragaini*[a]
Abstract:
Palladium
complexes
with
4,7-dimethoxy-1,10-
context of conducting polymers, where polypyrroles have found
many useful applications.[13]
phenanthroline as ligand catalyze the reductive cyclization of
nitrodienes using carbon monoxide as the reductant to give pyrroles.
Carbon dioxide is the only stoichiometric byproduct. Yields are good
and the starting materials can be easily synthesized in two steps by
a cross-aldol condensation followed by a Henry reaction. Different
substitution patterns are possible with this novel synthetic strategy.
Consequently, many new synthetic methods have been
developed for the construction of pyrroles and their derivatives.
Classical methods for the synthesis of substituted pyrroles
include the Knorr reaction,[14] the Hantzsch reaction,[15] and the
Paal-Knorr condensation.[16] However, these methods have
some limitations with respect to the regioselectivity, the
substitution patterns that can be introduced, multistep synthetic
operations and harsh reaction conditions. Despite recent
Introduction
advances,
particularly
in transition
metal-catalyzed,[17]
multicomponent processes[18] and domino reactions,[19] still novel
and highly efficient chemical reaction that can be used to
construct the skeleton of pyrroles with readily accessible
substrates and in few steps remains an attractive goal. Over the
past several years, metal catalyzed reductive condensation of a
nitro and an olefin group for the construction of heterocyclic
rings has been shown to be an effective, promising, extremely
The pyrrole nucleus is one of the most important heterocyclic
moieties, abundantly found in bioactive natural molecules,
forming the characteristic subunit of heme,[1] chlorophyll,[2]
vitamin B12[3] as well as in melanin pigments.[4] 1,2,5-
Trisubstituted pyrroles display interesting biological properties,
such as anti-inflammatory,[5] antipsychotic,[6] spasmolytic,[7] and
radioprotective.[8] Two clinical examples of pyrroles displaying
powerful method.[20] [21]
Nitroarenes have exclusively been used
,
this
pattern
of
substitution
are
amtolmetin
and
as substrates for many years, but recently the use of
nitroalkenes bearing in the beta position an aryl[22] or thienyl[23]
moiety has been reported as an alternative strategy to construct
nitrogen heterocycles in which the pyrrole nucleus is fused with
the originally present aromatic ring (Scheme 1).
tolmetin.[9](nonsteroidal anti-inflammatory agents) (Chart 1).
Generally pharmaceuticals containing pyrroles are of high value
as biological agents such as sunitinib [10] (anti-tumour), keterolac
[11]
(analgesic) and the highly successful cholesterol-lowering
drug atorvastatin calcium (Lipitor), which is notable as the first
Scheme 1: Traditional and more recent approaches to the synthesis of N-
heterocycles by reduction of organic nitro compounds.
Inspired by the importance of pyrrole derivatives and as an
extension of our previous work, we report here our results on the
developed of a new, facile and efficient synthesis for some
pyrrole derivatives by reductive cyclization of nitrodienes, using
palladium/phenanthroline as the catalyst and carbon monoxide
as the reductant. The reaction proceeds through the activation of
a diene C-H bond in the delta position relative to the nitro group
and no aryl ring is directly involved in the reaction (Scheme 2).
Figure 1: Important pharmaceutical drugs containing the pyrrole nucleus.
drug to earn in excess of $1 billion of sales in its first year.[12]
The electronic properties of pyrrole are important in the
[a]
Dr .M. A. EL-Atawy , Dr. F. Ferretti, Prof. Dr. F. Ragaini
Dipartimento di Chimica
Università degli Studi di Milano
Via Golgi 19, 20133 Milano, Italy
E-mail: fabio.ragaini@unimi.it
http://www.unimi.it/chiedove/cv/ENG/fabio_ragaini.pdf?1516461529
646
Scheme 2. Synthesis of pyrroles from nitrodienes.
[b]
Dr .M. A. EL-Atawy
Chemistry Department, Faculty of Science
Alexandria University
We are not aware of previous report of transition metal
catalyzed reduction of nitrodienes by carbon monoxide to give
P.O. 426 Ibrahemia, Alexandria 21321 (Egypt)
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.201701814
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pyrroles. To our knowledge, only a single reaction has been
mentioned in which this cyclization was effected by use of a
stoichiometric amount of P(OEt)3 (a Cadogan-type reaction).[24]
It should be recalled that we previously reported a synthesis
of pyrroles by reduction of nitroarenes by CO in the presence of
a conjugated diene. Oxazines are formed as intermediates in
this
case
(Scheme
3,
Ar-BIAN
=
bis-
Scheme 5. Synthesis of 2-methyl-5-phenyl-1H-pyrrole (2a)
(arylimino)acenaphthene).[25] However, that strategy only affords
N-arylpyrroles, whereas the presently described reaction gives
N-unsubstituted compounds.
Encouraged by this result, we explored the scope of this
reaction by applying it to a variety of differently substituted 1-
nitro-1,3-butadienes (1a-1q, Table 1 and Scheme 6). Although
this screening is not to be considered exhaustive and other
substitution patterns are surely compatible with our protocol, it is
evident that 2,5-disubstituted or 2,3,5-trisubstituted pyrroles can
be obtained in moderate to good isolated yields (34-83%). Both
strongly electronwithdrawing (-CF3, 1g) and strongly
electrondonating (-NMe2, 1c, 1d) substituents are well tolerated.
The best result was obtained for the reductive cyclization of 1d
to 2d (Table 1). Reductive cyclization of compounds 1a-1l
afforded disubstituted pyrrole in
a good yield, whereas
Scheme 3. N-Arylpyrrole synthesis from nitroarenes and dienes.
cyclization to trisubstituted pyrrole 2m, 2n, 2o and 2p gave
lower and moderate yields. This can be correlated to the steric
hindrance of the three substituents in the latter case, which
hinders the cyclization step. Worth of note, the reaction is
compatible with the presence of a second pyrrole, furan, or
thiophene ring in the molecule (2i-2l, 2o, 2p). Such products
belong to compound classes that can find applications for their
optoelectronic properties.
Results and Discussion
The starting nitrodienes were prepared by Henry
condensation of a nitroalkane with an α-β-unsaturated aldehyde.
The latter was in turn obtained by cross-aldol condensation
(Scheme 4. See the experimental part for details).
To test the relative ease of the present cyclization reaction
with respect to the classical cyclization of an o-nitrostyrene to
give
an
indole,
we
prepared
(1E,3E)-4-nitro-1-(2-
nitrophenyl)penta-1,3-diene (1q). This compound bears both a
nitro group on the diene moiety and one on the aryl group. Thus,
it may cyclize either by reduction of the former (to give pyrrole
2q) or by reduction of the latter (to give indole 3q). Both may
further cyclize to 2-methyl-1,4-dihydropyrrolo[3,2-b]indole
(Scheme 6). However, from the reaction mixture after the end of
the reaction, only indole 3q could be isolated (56% yield). Since
the slow step of this kind of reductive cyclization has been
shown to be the initial nitro group reduction in all the cases in
which the kinetic has been investigated,[21e, 26] this indicates that
the reduction of the nitro group bound to the aryl ring is faster
than that of nitrodiene. Moreover, no 1,4-dihydropyrrolo[3,2-
b]indole could be obtained even if isolated 3q was employed as
reagent for a second reaction under the same experimental
conditions of the first. The electron-rich nature of the indole
moiety is likely responsible for the lack of reactivity of 3q. Indeed
the initial reduction step of nitroarenes by metal complexes has
been shown to be an electron transfer from the metal complex to
the nitro group in all the cases in which this step has been
experimentally analyzed[27] and electrondonating substituents
are well known to make this reduction more difficult.
Scheme 4. Synthesis of the starting nitrodienes
Recently we reported an extensive work on the optimization
of a palladium catalytic system for the reductive cyclization of 1-
(thien-2-yl)-2-nitropropene
to
4H-5-methyl-thieno[3,2-
b]pyrrole.[23] The best experimental conditions were
[Pd(Phen)2][BF4]2 (2 mol%) as catalyst, 4,7-dimethoxy-1,10-
phenanthroline (16 mol%) as ligand, under 5 bar of CO and at
150 °C for 3 h, in the presence of Et3N (400 μl) and in
acetonitrile as the solvent. We tested the same conditions to
cyclize (1E,3E)-4-nitro-1-phenylpenta-1,3-diene (1a) into 2-
methyl-5-phenyl-1H-pyrrole (2b) and we were pleased to
observe that 1a was completely consumed, affording 2a in a
76% isolated yield (Scheme 5).
In this light, it should also be noted that the high yields
obtained in the case of substrates having
a
strongly
electrondonating substituent on the aryl ring (1c-1f) were initially
not expected. Indeed, for all reactions of this kind we previously
investigated employing nitroarenes as substrates, very poor
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Table 1. Substrate scope.[a]
Entry
Substrate
Product
Yield
(%)[b]
Scheme 6. Alternative reaction pathways for the reductive cyclization of
(1E,3E)-4-nitro-1-(2-nitrophenyl)penta-1,3-diene (1q)
yields or no reaction at all were observed when a methoxy or
dimethylamino group was directly connected to the
nitroarene.[20a] An intermediate outcome was observed when the
cyclization of β-nitrostyrenes was investigated, where an olefinic
bond is spacing the nitro and the aryl groups.[22b] Good results
were obtained when a methoxy group was present, but the yield
dropped in the presence of a dimethylamino substituent. In the
present case, two double bonds keep the electron rich ring far
from the nitro group. This is apparently enough to insulate the
two groups to the point that negative effects are not detected,
although it should also be considered that the use of the electron
rich 4,7(MeO)2Phen ligand surely plays a role in allowing the
reaction to run smoothly. The same combination of
spacing/electron rich ligand is responsible for the successful
cyclization of substrates containing the very electron rich pyrrole,
furan, and thiophene rings (substrates 1i-1l, 1o, 1p). Note that in
the case of the latter compounds, difficulties in isolating in a pure
form the quite reactive products surely account in part for the
lower isolated yields.
As far as the reaction mechanism is concerned, we propose
it to proceed similarly to what it occurs in other related transition-
metal catalyzed deoxygenation of organic nitro compounds by
carbon monoxide, leading to heterocycles (Scheme 7).
[a] Reaction conditions:
1 (0.5 mmol), [Pd(Phen)2][BF4]2 (0.01 mmol),
(MeO)2Phen (0.08 mmol), CH3CN (15 mL), Et3N (400 μl, 2.9 mmol), 150 °C,
PCO = 5 bar, for 3h. [b] Isolated yield.
Scheme 7. Proposed mechanism for the reductive cyclization of 1a to 2a.
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(E)-2-methyl-3-(thiophen-2-yl)acrylaldehyde,[37]
methylthiophen-2-yl)acrylaldehyde,[38]
yl)acrylaldehyde.[39] If not otherwise stated, all the other reagents were
purchased from Aldrich or Alfa-Aesar and used without further
purification. 1H, 13C and 2D (COSY, NOESY) NMR spectra were
recorded on a Bruker Avance DRX 300 or on a Bruker Avance DRX 400,
operating at 300 and 400 MHz respectively.
(E)-2-methyl-3-(5-
(E)-2-methyl-3-(thien-3-
The first step of this reaction pathway is the already
mentioned initial electron transfer from the metal complex to the
nitroarene. The formation of a delocalized radical anion and the
easy cis/trans isomerization of such a type of compound explain
why the cyclization occurs even if the orientation of the nitro
group in the starting material would not allow it to approach the
distal C=C double bond. The radical couple than collapses with
liberation of CO2 and formation of a nitrosodiene. The latter is
involved in the cyclization step to give a N-hydroxypyrrole. That
the cyclization reaction occurs at this stage and not from a
nitrene intermediate (or imido complex) generated by further
reduction of the nitroso compound, as often proposed in the
older literature, is strongly indicated by the isolation of N-hydroxy
Synthesis and characterization of substituted nitrodiene
Nitrodienes were prepared by Henry condensation between the
corresponding α,β-unsaturated aldehyde and the appropriate nitroalkane.
In a Schlenk flask, the aldehyde (10 mmol) and ammonium acetate (5
mmol) were dissolved in nitroethane (5 ml). The mixture was stirred at
reflux for 5 hours and the conversion of the aldehyde checked by TLC on
silica gel. The mixture was then allowed to cool to room temperature and
the solvent was evaporated. The residue was taken up with CH2Cl2 and
washed with water. The organic layer was dried (Na2SO4) and
evaporated in vacuo. Finally, purification over a short silica column with
EtOAc: hexane as the eluent afforded the olefin.[40]
derivatives (e.g. N-hydroxyindoles) during several similar
26, 28]]
reactions and by theoretical calculations.[21d,
Further
deoxygenation of the N-hydroxypyrrole by carbon monoxide
finally affords the product.
Conclusions
In this work, we have reported a novel palladium-catalyzed
reductive cyclization of nitrodienes employing carbon monoxide
as the reductant and affording carbon dioxide as the only
stoichiometric byproduct. The method is versatile and moderate
to good yields of the products can be obtained. Both strongly
electronwithdrawing (-CF3) and strongly electrondonating
(-NMe2) substituents are well tolerated. Because of our interests,
we mainly focused our synthetic attempts to some model
(1E,3E)-4-Nitro-1-phenylpenta-1, 3-diene (1a) [41]
Henry condensation between cinnamaldehyde and nitroethane. Yellow
solid, yield 67%. 1H NMR (400 MHz, CDCl3, 300 K): δ = 7.80 (d, J = 11.5
Hz, 1H, Hdiene), 7.57 – 7.52 (m, 2H, HPh), 7.46 – 7.35 (m, 3H, HPh), 7.12 (d,
J = 15.4 Hz, 1H, Hdiene), 6.92 (dd, J = 15.4, 11.5 Hz, 1H, Hdiene), 2.39 (s,
3H, CH3) ppm. 13C NMR (101 MHz, CDCl3, 300 K): δ = 143.93 (CH),
135.64 (C), 133.64 (CH), 130.06 (CH), 129.05 (CH), 127.77 (CH), 121.48
(CH), 13.17 (CH3) ppm. One quaternary carbon was not detected.
Spectral data of the compound are in accordance with those reported in
the literature. C11H11NO2 requires: C, 69.83; H, 5.86; N, 7.40%. Found: C,
70.20; H, 6.00; N, 7.05%.
substrates and to compounds containing
a second five-
membered ring. However, the reaction never failed in any of our
attempts and it is clear that it should work well even for a much
broader class of compounds. Worth of note, the starting
materials can be obtained in a simple way from cheap products
and without the need for expensive reagents at any stage of the
process. Thus, the synthesis is amenable to scale up even at
the production scale in an economically competitive way.
(1E,3E)-4-Nitro-1-phenylhexa-1,3-diene (1b)
Henry condensation between cinnamaldehyde and nitropropane. Yellow
solid, yield 53%. 1H NMR (300 MHz, CDCl3, 300 K): δ = 7.73 (d, J = 11.4
Hz, 1H, Hdiene), 7.59 – 7.30 (m, 5H, HPh), 7.12 (d, J = 15.5 Hz, 1H, Hdiene),
6.92 (dd, J = 15.5, 11.5 Hz, 1H, Hdiene), 2.84 (q, J = 7.4 Hz, 2H, CH2),
1.24 (t, J = 7.4 Hz, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3, 300 K): δ =
152.59 (C), 144.43 (CH), 136.12 (C), 133.55 (CH), 130.26 (CH), 129.38
(CH), 127.94 (CH), 121.36 (CH), 20.84 (CH2), 13.41 (CH3) ppm.
C12H13NO2 requires: C, 70.92; H, 6.45; N, 6.89%. Found: C 70.64; H
6.43; N 6.97 %
Experimental Section
Unless otherwise stated, all reactions were conducted under a dinitrogen
atmosphere. All the solvents used in catalytic reactions, were dried by
distillation over CaH2 and stored under a dinitrogen atmosphere. All
glassware and magnetic stirring bars were kept in an oven at 125 °C for
at least two hours and let to cool under vacuum before use. 1,10-
Phenanthroline (Phen), purchased as the hydrate, was dried over
Na2SO4 after dissolution in CH2Cl2, followed by filtration under a
dinitrogen atmosphere and evaporation of the solvent in vacuo. Then, it
was stored under dinitrogen. 4,7-Dimethoxy-1,10-phenathroline
((MeO)2Phen) was synthesized as reported in the literature.[29] Both
phenanthrolines can be weighed in the air, but must be stored in an inert
atmosphere to avoid water uptake. [Pd(Phen)2][BF4]2, was synthesized
following the procedure reported in the literature.[30] α,β-Unsaturated
aldehydes were prepared by cross aldol condensation.[31] They are all
known compounds and their spectroscopic characterization matched the
published data ((E)-3-(4-(trifluoromethyl)phenyl)acrylaldehyde,[32] (E)-3-
(4-fluorophenyl)acrylaldehyde,[33] (E)-3-(1H-pyrrol-2-yl)acrylaldehyde,[34]
N,N-Dimethyl-4-((1E,3E)-4-nitrohexa-1,3-dienyl)aniline (1c)
Henry condensation between 4-dimethylaminocinnamaldehyde and
nitropropane. Dark purple solid, yield 85%. 1H NMR (300 MHz, CDCl3): δ
= 7.78 (d, J = 11.2 Hz, 1H, Hdiene), 7.44 (d, J = 8.8 Hz, 2H, HAr), 7.04 (d, J
= 15.1 Hz, 1H, Hdiene), 6.72 (m, 3H, HAr and Hdiene), 3.06 (s, 6H, CH3),
2.80 (q, J = 7.4 Hz, 2H, CH2), 1.21 (t, J = 7.4 Hz, 3H, CH3) ppm. 13C
(E)-3-(fur-2-yl)acrylaldehyde,[35]
(E)-3-(thiophen-2-yl)acrylaldehyde,[36]
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10.1002/ejoc.201701814
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2
NMR (75 MHz, CDCl3) δ 151.68 (C), 149.11 (C), 145.02 (CH), 135.29
(CH), 129.37 (CH), 124.21 (C), 116.30 (CH), 112.06 (CH), 40.20 (CH3),
20.37 (CH2), 12.92 (CH3) ppm. C14H18N2O2 requires: C, 68.27; H, 7.37; N,
11.37%. Found: C, 68.43; H, 7.22; N, 11.20%.
147.70 (C), 141.62 (CH), 139.00 (C), 132.58 (CH), 131.36 (q, JC,F
=
31.71 Hz, C), 127.65 (CH), 125.88 (q,3JC,F = 3.6 Hz, CH), 124.85 (q, 1JC,F
= 270 Hz, CF3), 123.58 (CH), 13.18 (CH3) ppm. C12H10F3NO2 requires:
C, 56.04; H, 3.92; N, 5.45%. Found: C, 56.11; H, 3.98; N, 5.26%.
1-Fluoro-4-((1E,3E)-4-nitrohexa-1,3-dienyl)benzene (1h)
N,N-Dimethyl-4-((1E,3E)-4-nitropenta-1,3-dienyl)aniline (1d)
Henry condensation between 4-fluorocinnamaldehyde and nitropropane.
Orange solid, yield 74%. 1H NMR (600 MHz, CDCl3): δ = 7.71 (d, J =
11.6 Hz, 1H, Hdiene), 7.53 (dd, J = 8.8, 5.4 Hz, 2H, HAr), 7.15 – 7.05 (m,
3H, HAr and Hdiene), 6.84 (dd, J = 15.4, 11.6 Hz, 1H, Hdiene), 2.83 (q, J =
7.4 Hz, 2H, CH2), 1.23 (t, J = 7.5 Hz, 3H, CH3) ppm. 13C NMR (150 MHz,
Henry condensation between 4-dimethylaminocinnamaldehyde and
nitroethane. Dark purple solid, yield 87%. 1H NMR (300 MHz, CDCl3): δ =
7.83 (d, J = 11.7 Hz, 1H, Hdiene), 7.44 (d, J = 8.7 Hz, 2H, HAr), 7.04 (d, J =
15.2 Hz, 1H, Hdiene), 6.77 – 6.61 (m, 3H, HAr and Hdiene), 3.06 (s, 6H, CH3),
2.35 (s, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 151.37 (C),
145.29 (CH), 143.39 (C), 135.67 (CH), 129.54 (CH), 124.15 (C), 116.66
(CH), 112.20 (CH), 40.35 (CH3), 12.88 (CH3) ppm. C13H16N2O2 requires:
C, 67.22; H, 6.94; N, 12.06%. Found: C, 67.25; H, 6.71; N, 11.79%.
1
CDCl3): δ = 162.81 (d, JCF = 237.1 Hz, CF), 152.42 (C), 142.61 (CH),
3
133.35 (CH), 132.23 (C), 129.43 (d, JCF = 8.2 Hz, CH), 120.73 (CH),
2
116.22 (d, JCF = 21.8 Hz, CH), 20.38 (CH2), 12.94 (CH3) ppm.
C12H12FNO2 requires: C, 65.15; H, 5.47; N, 6.33%. Found: C, 65.08; H,
5.42; N, 6.14%.
1-Methoxy-4-((1E,3E)-4-nitrohexa-1,3-dienyl)benzene (1e) [42]
2-((1E,3E)-4-Nitropenta-1,3-dienyl)-1H-pyrrole (1i)
Henry
condensation
between
4-methoxycinnamaldehyde
and
nitropropane. Orange solid, yield 89%. 1H NMR (400 MHz, CDCl3): δ =
7.71 (d, J = 11.6 Hz, 1H, Hdiene), 7.48 (d, J = 8.6 Hz, 2H, HAr), 7.04 (d, J =
15.3 Hz, 1H, Hdiene), 6.91 (t, J = 9.5 Hz, 2H, HAr), 6.78 (dd, J = 15.2, 11.7
Hz, 1H, Hdiene), 3.85 (s, 3H, CH3), 2.80 (q, J = 7.4 Hz, 2H, CH2), 1.21 (t, J
= 7.4 Hz, 3H, CH3) ppm. 13C NMR (101 MHz, CDCl3): δ = 161.05 (C),
150.79 (C), 144.04 (CH), 133.99 (CH), 129.24 (CH), 128.69 (C), 118.75
(CH), 114.46 (CH), 55.31 (CH3), 20.38 (CH2), 12.97 (CH3) ppm. Spectral
data of the compound are in accordance with those reported in the
literature. C13H15NO3 requires: C, 66.94; H, 6.48; N, 6.00%. Found: C,
67.09; H, 6.44; N, 5.96%.
Henry condensation between (E)-3-(1H-pyrrol-2-yl)acrylaldehyde and
nitroethane. Violet crystals, yield 83%. 1H NMR (600 MHz, CDCl3): δ =
8.74 (br s, 1H, NH), 7.80 (d, J = 11.7 Hz, 1H, Hdiene), 6.96 (m, 2H, Hdiene,
and Hpyrrole ), 6.59 (s, 1H, Hpyrrole), 6.49 (dd, J = 15.3, 11.8 Hz, 1H, Hdiene),
6.32 (br s, 1H, Hpyrrole), 2.34 (s, 3H, CH3) ppm. 13C NMR (150 MHz,
CDCl3): δ = 143.90 (C), 135.34 (CH), 133.79 (CH), 130.31 (C), 122.75
(CH), 115.89 (CH), 113.88 (CH), 111.53 (CH), 13.02 (CH3) ppm.
C9H10N2O2 requires: C, 60.66; H, 5.66; N, 15.72%. Found: C, 60.82; H,
5.64; N, 15.57%.
(1E,3E) 4-Nitro-1-fur-2-ylpenta-1,3-diene (1J)
1-Methoxy-4-((1E,3E)-4-nitropenta-1,3-dienyl)benzene (1f) [42]
Henry condensation between (E)-3-(fur-2-yl)acrylaldehyde and
nitroethane. Yellow solid, yield 70%. 1H NMR (300 MHz, CDCl3, 300 K): δ
= 7.72 (d, J = 9.8 Hz, 1H, Hdiene), 7.50 (br s, 1H, Hfuran), 6.91 – 6.71 (m,
2H, Hdiene), 6.57 (d, J = 3.4 Hz, 1H, Hfuran), 6.50 (dd, J = 3.4, 1.8 Hz, 1H,
Hfuran), 2.35 (s, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3, 300 K): δ =
152.42 (C), 146.61 (C), 144.89 (CH), 133.81 (CH), 130.31 (CH), 119.96
(CH), 113.92 (CH), 113.02 (CH), 13.42 (CH3) ppm. C9H9NO3 requires: C,
60.33; H, 5.06; N, 7.82%. Found: C, 60.56; H, 4.93; N, 7.86%.
Henry condensation between 4-methoxycinnamaldehyde and nitroethane.
Orange solid, yield 54%. 1H NMR (300 MHz, CDCl3): δ = 7.80 (d, J =
11.6 Hz, 1H, Hdiene), 7.49 (d, J = 8.7 Hz, 2H, HAr), 7.06 (d, J = 15.4 Hz,
1H, Hdiene), 6.94 (d, J = 8.7 Hz, 2H, HAr), 6.78 (dd, J = 15.3, 11.6 Hz, 1H,
Hdiene), 3.87 (s, 1H, OCH3), 2.37 (s, 3H, CH3) ppm. 13C NMR (100 MHz,
CDCl3): δ = 161.09 (C), 145.26 (C), 143.83 (CH), 134.41 (CH), 129.19
(CH), 128.64 (C), 119.13 (CH), 114.41 (CH), 55.29 (OCH3), 13.07 (CH3)
ppm. Spectral data of the compound are in accordance with those
reported in the literature. C12H13NO3 requires: C, 65.74; H, 5.98; N,
6.39%. Found: C, 65.70; H, 5.98; N, 6.31%.
(1E,3E) 4-Nitro-1-fur-2-ylhexa-1,3-diene (1k)
Henry condensation between (E)-3-(fur-2-yl)acrylaldehyde and
nitropropane. Orange solid, yield = 66 %. 1H NMR (300 MHz, CDCl3): δ
7.65 (d, J = 9.6 Hz, 1H, Hdiene), 7.50 (br s, 1H, Hfuran), 6.93 – 6.68 (m, 2H,
Hdiene), 6.55 (d, J = 3.4 Hz, 1H, Hfuran), 6.49 (dd, J = 3.2, 1.7 Hz, 1H,
Hfuran), 2.79 (q, J = 7.4 Hz, 2H, CH2), 1.19 (t, J = 7.4 Hz, 3H, CH3) ppm.
13C NMR (75 MHz, CDCl3): δ = 152.47 (C), 152.20 (C), 144.90 (CH),
133.34 (CH), 130.32 (CH), 119.60 (CH), 114.05 (CH), 112.94 (CH),
20.75 (CH2), 13.32 (CH3) ppm. C10H11NO3 requires: C, 62.17; H, 5.74; N,
7.25%. Found: C, 62.03; H, 5.71; N, 7.11%.
1-((1E,3E)-4-Nitropenta-1,3-dienyl)-4-(trifluoromethyl)benzene (1g)
Henry condensation between 4-trifluoromethylcinnamaldehyde and
nitroethane. Yellowsolid, yield 93%. 1H NMR (600 MHz, CDCl3): δ = 7.78
(d, J = 11.5 Hz, 1H, Hdiene), 7.67 (d, J = 8.5 Hz, 2H, HAr), 7.64 (d, J = 8.3
Hz, 2H, HAr), 7.12 (d, J = 15.5 Hz, 1H, Hdiene), 6.99 (dd, J = 15.5, 11.4 Hz,
1H, Hdiene), 2.41 (s, 3H, CH3) ppm. 13C NMR (150 MHz, CDCl3): δ =
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10.1002/ejoc.201701814
European Journal of Organic Chemistry
FULL PAPER
(300 MHz, CDCl3, 300 K): δ = 7.79 (s, 1H, Hdiene), 7.02 (d, J = 3.7 Hz, 1H,
Hthioph), 6.94 (s, 1H, Hdiene), 6.79 (dd, J = 3.7, Hz, 1H, Hthioph), 2.55 (s, 3H,
CH3), 2.45 (s, 3H, CH3), 2.27 (s, 3H, CH3) ppm. 13C NMR (75 MHz,
CDCl3, 300 K): δ = 145.66 (C), 144.44 (C), 139.48 (CH), 137.92 (C),
133.84 (CH), 131.69 (CH), 127.45 (C), 126.21 (CH), 18.16 (CH3), 15.92
(CH3), 14.75 (CH3) ppm. C11H13NO2S requires: C, 59.17; H, 5.87; N,
6.27%. Found: C, 59.21; H, 5.86; N, 6.20%.
2-((1E,3E)-4-Nitrohexa-1,3-dienyl)thiophene (1l)
Henry condensation between (E)-3-(thien-2-yl)acrylaldehyde and
nitropropane. Red oil, yield 88%. 1H NMR (600 MHz, CDCl3): δ = 7.67 (d,
J = 11.7 Hz, 1H, Hdiene), 7.39 (d, J = 5.0 Hz, 1H, Hthiop), 7.23 – 7.19 (m,
2H, Hthioph and Hdiene), 7.08 (dd, J =5.0, 3.4 Hz, 1H, Hthioph), 6.68 (dd, J
=15.2, 11.7 Hz, 1H, Hdiene), 2.79 (q, J = 7.4 Hz, 2H, CH2), 1.22 (t, J = 7.4
Hz, 3H, CH3) ppm. 13C NMR (150 MHz, CDCl3): δ = 151.68 (C), 141.33
(C), 136.39 (CH), 133.07 (CH), 129.85 (CH), 128.36 (CH), 128.07 (CH),
120.43 (CH), 20.52 (CH2), 13.08 (CH3) ppm. C10H11NO2S requires: C,
57.39; H, 5.30; N, 6.69%. Found: C, 57.68; H, 5.42; N, 6.39%.
(1E,3E)-4-Nitro-1-(2-nitrophenyl)penta-1,3-diene
Henry condensation between o-nitrocinnamaldehyde and nitroethane.
Yellow solid, yield = 92%. 1H NMR (300 MHz, CDCl3, 300 K): δ = 8.06 (d,
J = 8.1 Hz, 1H, Hdiene), 7.80 (d, J = 11.6 Hz, 1H, Hdiene), 7.67 – 7.50 (m,
4H, HAr), 6.86 (dd, J = 15.2, 11.6 Hz, 1H, Hdiene), 2.40 (s, 3H, CH3). 13C
NMR (75 MHz, CDCl3, 300 K): δ = 158.62 (C), 148.47 (C), 138.62 (CH),
133.80 (CH), 132.65 (CH), 131.85 (C), 130.15 (CH), 128.96 (CH), 126.36
(CH), 125.61 (CH), 13.60 (CH3) ppm. C11H10N2O4 requires: C, 56.41; H,
4.30; N, 11.96%. Found: C, 56.52; H, 4.23; N, 12.00%.
(1E,3E)-2-Methyl-4-nitro-1-phenylpenta-1,3-diene (1m)
Henry condensation between trans-α-methylcinnamaldehyde and
nitroethane. Yellow solid, yield 52%. 1H NMR (400 MHz, CDCl3, 300 K): δ
= 7.77 (s, 1H, Hdiene), 7.49 – 7.31 (m, 5H, HAr), 6.85 (s, 1H, Hdiene), 2.47 (s,
3H, CH3), 2.20 (s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 300 K): δ =
146.43 (C), 139.27 (CH), 138.34 (CH), 136.18 (C), 131.29 (C), 129.49
(CH), 128.48 (CH), 128.14 (CH), 17.80 (CH3), 14.34 (CH3) ppm.
C12H13NO2 requires: C, 70.92; H, 6.45; N, 6.89%. Found: C, 71.16; H,
6.33; N, 6.83%.
Typical Catalytic Reaction
The catalyst, [Pd(Phen)2][BF4]2 (0.01 mmol), the ligand, (MeO)2Phen
(0.08 mmol), and the nitrodiene (0.50 mmol) were weighed in the air in a
glass liner and then placed inside a Schlenk tube with a wide mouth
under a dinitrogen atmosphere. The solvent, CH3CN (15 mL), and Et3N
(400 μl, 2.9 mmol), were added by volume and the liner was closed with
a screw cap having a glass wool-filled open mouth that allows gaseous
reagents to exchange. The resulting solution was stirred for 10 minutes
and then the Schlenk tube was immersed in liquid nitrogen until the
solvent froze and evacuated and filled with dinitrogen for three times. The
liner was rapidly transferred to a 200 mL stainless steel autoclave
equipped with magnetic stirring. The autoclave was then evacuated and
filled with dinitrogen three times. CO, 5 bar, was charged at room
temperature and the autoclave was immersed in an oil bath preheated at
150 °C and stirred at this temperature for 3h.. At the end of the reaction,
the autoclave was quickly cooled with an ice bath, and vented. The
substrate scope was investigated by isolating the products by column
chromatography (gradient elution from hexane to hexane/AcOEt 9:1 with
the addition of 1% Et3N).
(1E,3E)-2-Methyl-4-nitro-1-phenylhexa-1,3-diene (1n)
Henry condensation between α-methylcinnamaldehyde and nitropropane.
Yellow oil, yield 44%. 1H NMR (300 MHz, CDCl3, 300 K ): δ = 7.71 (s, 1H,
Hdiene), 7.51 – 7.32 (m, 5H, HAr), 6.86 (s, 1H, Hdiene), 2.92 (q, J = 7.4 Hz,
2H, CH2), 2.18 (s, 3H, CH3), 1.25 (t, J = 7.4 Hz, 3H, CH3) ppm. 13C NMR
(75 MHz, CDCl3, 300 K): δ = 152.35 (C), 139.07 (CH), 138.27 (CH),
136.69 (C), 131.62 (C), 129.79 (CH), 128.84 (CH), 128.47 (CH), 21.55
(CH2), 17.85 (CH3), 13.71 (CH3) ppm. C13H15NO2 requires C, 71.87; H,
6.96; N, 6.45%. Found: C, 72.17; H, 7.15; N, 6.05%.
Characterization of pyrroles
(1E,3E)-2-Methyl-4-nitro-1-thien-2-ylpenta-1,3-diene (1o)
Henry condensation between (E)-2-methyl-3-(thien-3-yl)acrylaldehyde
and nitroethane. Yellow oil, yield = 53%. 1H NMR (300 MHz, CDCl3, 300
K ): δ = 7.79 (s, 1H, Hdiene), 7.48 (d, J = 5.0 Hz, 1H, Hthioph), 7.22 (d, J =
3.6 Hz, 1H, Hthioph), 7.12 (dd, J = 5.0, 3.6 Hz, 1H, Hthioph), 7.01 (s, 1H,
Hdiene), 2.47 (s, 3H, CH3), 2.30 (s, 3H, CH3) ppm. 13C NMR (75 MHz,
CDCl3): δ = 146.30 (C), 140.04 (C), 138.92 (CH), 132.75 (CH), 131.09
(CH), 129.09 (C), 128.86 (CH), 127.99 (CH), 18.47 (CH3), 14.93 (CH3)
ppm. C10H11NO2S requires: C, 57.39; H, 5.30; N, 6.69%. Found: C,
57.49; H, 5.35; N, 6.45;
2-Methyl-5-phenyl-1H-pyrrole (2a) [43]
White solid, yield 76%. 1H NMR (300 MHz, CDCl3, 300 K ): δ = 8.13 (br s,
exchangeable, 1H, NH), 7.46 (d, J = 7.9 Hz, 2H, HAr), 7.37 (t, J = 7.7 Hz,
2H, HAr), 7.19 (t, J = 7.3 Hz, 1H, HAr), 6.43 (br s, 1H, Hpyrrole), 5.99 (br s,
1H, Hpyrrole ), 2.37 (s, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3, 300 K): δ
= 133. 53 (C), 131.20 (C), 129.42 (C), 129.21 (CH), 126.05 (CH), 123.74
(CH), 108.36 (CH), 106.61 (CH), 13.58 (CH3) ppm. C11H11N requires: C,
84.04; H, 7.05; N, 8.91%. Found: C, 84.18; H, 6.69; N, 8.60%. Spectral
data of the compound are in accordance with those reported in the
literature
(1E,3E)-2-Methyl-4-nitro-1-(5-methylthien-2-yl)penta-1,3-diene (1p)
Henry condensation between (E)-2-methyl-3-(5-methylthiophen-2-
yl)acrylaldehyde and nitroethane. Orange solid, yield = 32%. 1H NMR
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10.1002/ejoc.201701814
European Journal of Organic Chemistry
FULL PAPER
2-Ethyl-5-phenyl-1H-pyrrole (2b) [44]
White solid, yield 69%. 1H NMR (300 MHz, CDCl3): δ = 8.02 (br s,
exchangeable, 1H, NH), 7.38 (d, J = 8.8 Hz, 2H, HAr), 6.92 (d, J = 8.8 Hz,
2H, HAr), 6.30 (t, J = 3.0 Hz, 1H, Hpyrrole), 5.98 - 5.94 (m, 1H, Hpyrrole), 3.84
(s, 3H, CH3), 2.35 (s, 3H, CH3) ppm.13C NMR (75 MHz, CDCl3): δ =
158.10 (C), 130.83 (C), 128.36 (C), 126.30 (C), 124.80 (CH), 114.30
(CH), 107.66 (CH), 105.15 (CH), 55.45 (CH3), 13.37 (CH3) ppm.
C12H13NO requires: C, 76.98; H, 7.00; N, 7.48%. Found: C, 77.07; H,
6.73; N, 7.32%. Spectral data of the compound are in accordance with
those reported in the literature
1
White solid, yield 72%. H NMR (400 MHz, CDCl3, 300 K): δ = 8.14 (br s,
exchangeable, 1H, NH), 7.47 (d, J = 7.9 Hz, 2H, HAr), 7.37 (t, J = 7.7 Hz,
2H, HAr), 7.19 (t, J = 7.3 Hz, 1H, HAr), 6.45 (br s, 1H, Hpyrrole), 6.02 (br s,
1H, Hpyrrole). 2.72 (q, J = 7.6 Hz, 2H, CH2), 1.33 (t, J = 7.6 Hz, 3H, CH3)
ppm. 13C NMR (100 MHz, CDCl3, 300 K): δ = 135.62 (C), 133.21 (C),
130.70 (C), 128.82 (CH), 125.79 (CH), 123.34 (CH), 106.38 (CH), 106.00
(CH), 21.09 (CH2), 13.71 (CH3) ppm. C12H13N: requires: C, 84.17; H,
7.65; N, 8.18%. Found: C, 84.11; H, 7.76; N, 8.05%. Spectral data of the
compound are in accordance with those reported in the literature
2-Methyl-5-(4-(trifluoromethyl)phenyl)-1H-pyrrole (2g) [47]
White solid, yield 79%. 1H NMR (400 MHz, CDCl3): δ = 8.20 (br s,
exchangeable, 1H, NH), 7.60 (d, J = 8.2 Hz, 2H, HAr), 7.52 (d, J = 8.2 Hz,
2H, HAr), 6.54 (t, J = 3.0 Hz, 1H, Hpyrrole), 6.03 (m, 1H, Hpyrrole), 2.38 (s, 3H,
CH3) ppm. 19F NMR (376 MHz, CDCl3): δ = -62.24. (s, CF3). 13C NMR
(101 MHz, CDCl3): δ = 136.21 (C), 130. 69 (C), 129.40 (C), 127.29 (q,
4-(5-Ethyl-1H-pyrrol-2-yl)-N,N-dimethylaniline (2c)
White solid, yield 76%. 1H NMR (300 MHz, CDCl3): δ = 8.04 (br s,
exchangeable, 1H, NH), 7.39 (d, J = 8.9 Hz, 2H, HAr), 6.80 (d, J = 8.9 Hz,
2H, HAr), 6.36 – 6.28 (m, 1H, Hpyrrole), 6.02 (m, 1H, Hpyrrole), 3.01 (s, 6H,
N(CH3)2), 2.73 (q, J = 7.5 Hz, 2H, CH2), 1.35 (t, J = 7.6 Hz, 3H, CH3)
ppm.13C NMR (75 MHz, CDCl3): δ = 149.15 (C), 134.28 (C), 131.68 (C),
124.94 (CH), 122.31 (C), 113.19 (CH), 105.73 (CH), 104.15 (CH), 40.66
(CH3), 21.04 (CH2), 13.70 (CH3) ppm. C14H18N2 requires: C, 78.46; H,
8.47; N, 13.07%. Found: C, 78.84; H, 8.41; N, 12.90.
3
1
2JC,F = 32.5 Hz, C), 126.00 (q, JC,F = 3.9 Hz, CH), 124.52 (q, JC,F
=
270.8 Hz, CF3), 123.08 (CH), 108.76 (CH), 108.27 (CH), 13.32 (CH3)
ppm. C12H10F3N requires: C, 64.00; H, 4.48; N, 6.22%. Found: C, 63.82;
H, 4.45; N, 6.12%. Spectral data of the compound are in accordance with
those reported in the literature
2-Ethyl-5-(4-fluorophenyl)-1H-pyrrole (2h)
N,N-Dimethyl-4-(5-methyl-1H-pyrrol-2-yl)aniline (2d)
White solid, yield 68%. 1H NMR (600 MHz, CDCl3): δ = 8.06 (br s,
exchangeable,1H, NH), 7.41 (dd, J = 8.8, 5.2 Hz, 2H, HAr), 7.07 (t, J = 8.7
Hz, 2H, HAr), 6.37 (t, J = 2.9 Hz, 1H, Hpyrrole), 6.01 (t, J = 2.9 Hz, 1H,
Hpyrrole), 2.71 (q, J = 7.7 Hz, 2H, CH2), 1.32 (q, J = 7.7 Hz, 3H, CH3) ppm.
19F NMR (376 MHz, CDCl3): δ = -117.01 (s, F) ppm. 13C NMR (150 MHz,
White solid, yield 83%. 1H NMR (300 MHz, CDCl3): δ = 7.99 (br s,
exchangeable, 1H, NH), 7.36 (d, J = 8.9 Hz, 2H, HAr), 6.77 (d, J = 8.9 Hz,
2H, HAr), 6.27 (t, J = 3.0 Hz, 1H, Hpyrrole), 5.96 (t, J = 3.0 Hz, 1H, Hpyrrole),
2.99 (s, 6H, N(CH3)2), 2.36 (s, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3):
δ = 148.93 (C), 131.59 (C), 127.75 (C), 124.70 (CH), 122.28 (C), 113.04
(CH), 107.44 (CH), 104.05 (CH), 40.84 (CH3), 13.17 (CH3) ppm.
C13H16N2 requires: C, 77.96; H, 8.05; N, 13.99 %. Found: C, 77.93; H,
7.64; N, 13.56.
1
CDCl3): δ = 161.22 (d, JC,F = 244.9 Hz, CF), 135.62 (C), 129.81 (C),
129.45 (C), 125.02 (d, 3JCF = 7.5 Hz, CH), 115.71 (d, 2JCF = 22.5 Hz, CH),
106.27 (CH), 105.90 (CH), 20.98 (CH2), 13.59 (CH3) ppm. C12H12FN
requires: C, 76.17; H, 6.39; N, 7.40%. Found: C, 75.93; H, 6.26; N,
7.22%.
2-Ethyl-5-(4-methoxyphenyl)-1H-pyrrole (2e) [45]
5-Methyl-1H,1'H-2,2'-bipyrrole (2i) [48]
White solid, yield 72%. 1H NMR (300 MHz, CDCl3): δ = 8.07 (br s,
exchangeable, 1H, NH), 7.41 (d, J = 8.8 Hz, 2H, HAr), 6.94 (d, J = 8.8 Hz,
2H, HAr), 6.35 (t, J = 2.9 Hz, 1H, Hpyrrole), 6.01 (t, J = 2.9 Hz, 1H, Hpyrrole),
3.86 (s, 3H, CH3), 2.72 (q, J = 7.6 Hz, 2H, CH2), 1.33 (t, J = 7.6 Hz, 3H,
CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 157.78 (C), 135.01 (C),
130.83 (C), 126.39 (C), 125.00 (CH), 114.43 (CH), 106.11 (CH), 104.74
(CH), 55.33 (CH3), 21.16 (CH2), 13.66 (CH3) ppm. C13H15NO requires: C,
77.58; H, 7.51; N, 6.96%. Found: C, 77.41; H, 7.47; N, 6.92%. Spectral
data of the compound are in accordance with those reported in the
literature
White solid (it turns into greenish white immediately if exposed to the air),
yield 34%. The low yield in this case is mainly due to the instability of the
product and its difficult isolation from the silica gel of the column, 1H NMR
(400 MHz, CDCl3): δ = 8.21 (br s, exchangeable, 1H, NH), 7.95 (br s,
exchangeable, 1H, NH), 6.76 (d, J = 1.0 Hz, 1H, Hpyrrole), 6.25 (dd, J = 5.6,
2.8 Hz, 1H, Hpyrrole), 6.18 (s, 1H, Hpyrrole), 6.10 (t, J = 2.8 Hz, 1H, Hpyrrole),
5.91 (s, 1H, Hpyrrole), 2.32 (s, 3H, CH3) ppm. 13C NMR (101 MHz, CDCl3):
δ = 127.67 (C), 126.22 (C), 124.62 (C), 117.21 (CH), 109.30 (CH),
107.02 (CH), 103.60 (CH), 102.90 (CH), 13.02 (CH3) ppm. C9H10N2
requires: C, 73.94; H, 6.89; N, 19.16%. Found: C, 73.81; H, 6.73; N,
19.12%. Spectral data of the compound are in accordance with those
reported in the literature
2-(4-Methoxyphenyl)-5-methyl-1H-pyrrole (2f) [46]
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10.1002/ejoc.201701814
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2-(Fur-2-yl)-5-methyl-1H-pyrrole (2j) [49]
Colorless oil, yield 43%. 1H NMR (300 MHz, CDCl3, 300 K): δ = 7.85 (br s,
exchangeable, 1H, NH), 7.55 – 7.34 (m, 4H, HAr), 7.34 – 7.20 (m, 1H,
HAr), 5.91 (s, 1H, Hpyrrole), 2.69 (q, J = 7.6 Hz, 2H, CH2), 2.29 (s, 3H, CH3),
1.32 (t, J = 7.6 Hz, 3H, CH3) ppm. 13C NMR (75 MHz, CDCl3, 300 K): δ =
134.59 (C), 134.46 (C), 129.04 (CH), 126.67 (C), 126.37 (CH), 125.87
(CH), 116.66 (C), 108.99 (CH), 21.26 (CH2), 14.00 (CH3), 12.95 (CH3).
C13H15N requires: C, 84.28; H, 8.16; N, 7.56%. Found: C, 84.59; H, 8.40;
N, 7.30%. Spectral data of the compound are in accordance with those
reported in the literature.
Colorless oil, yield 62%. 1H NMR (400 MHz, CDCl3): δ = 8.23 (br s,
exchangeable, 1H, NH), 7.35 (d, J = 1.4 Hz, 1H, Hfuran), 6.44 (dd, J = 3.3,
1.8 Hz, 1H, Hfuran), 6.34 (t, J = 2.9 Hz, 1H, Hpyrrole), 6.30 (d, J = 3.3 Hz, 1H,
Hfuran), 5.95 (m, 1H, Hpyrrole), 2.34 (s, 3H, CH3) ppm. 13C NMR (100 MHz,
CDCl3, 300 K): δ = 148.57 (C), 139.91 (CH), 128.39 (C), 122.73 (C),
111.42 (CH), 107.55 (CH), 105.63 (CH), 101.32 (CH), 13.04 (CH3) ppm.
C9H9NO requires: C, 73.45; H, 6.16; N, 9.52%. Found: C, 73.17; H, 6.27;
N, 9.35%. Spectral data of the compound are in accordance with those
reported in the literature.
3,5-Dimethyl-2-(thien-2-yl)-1H-pyrrole (2o)
2-(Fur-2-yl)-5-ethyl-1H-pyrrole (2k)
Colorless oil, yield 46%. 1H NMR (300 MHz, CDCl3, 300 K): δ = 7.79 (br s,
exchangeable, 1H, NH), 7.17 (dd, J = 5.1, 1.1 Hz, 1H, Hthioph.), 7.05 (dd, J
= 5.1, 3.6 Hz, 1H, Hthioph), 6.95 (dd, J = 3.6, 1.1 Hz, 1H, Hthioph).5.81 (s,
1H, Hpyrrole), 2.29 (s, 3H, CH3), 2.21 (s, 3H, CH3) ppm. 13C NMR (75 MHz,
CDCl3, 300 K ): δ = 131.54 (C), 128.02 (C), 127.75 (CH), 122.48 (CH),
121.99 (C), 121.44 (CH), 117.66 (C), 110.54 (CH), 13.34 (CH3), 12.76
(CH3) ppm. C10H11NS requires: C, 67.76; H, 6.25; N, 7.90%. Found: C,
68.01; H, 6.35; N, 7.63%.
Yellow oil, yield 49%. 1H NMR (400 MHz, CDCl3): δ = 8.25 (br s,
exchangeable, 1H, NH), 7.37 (dd, J = 1.8, 0.5 Hz 1H, Hfuran), 6.45 (dd, J =
3.3, 1.8 Hz, 1H, Hfuran), 6.38 (t, J = 3.0 Hz, 1H, Hpyrrole), 6.33 (d, J = 3.3
Hz, 1H, Hfuran), 6.05 – 5.94 (m, 1H, Hpyrrole), 2.70 (q, J = 7.6 Hz, 2H, CH2),
1.32 (t, J = 7.6 Hz, 3H, CH3) ppm. 13C NMR (101 MHz, CDCl3): δ =
148.64 (C), 139.92 (CH), 134.96 (C), 122.67 (C), 111.60 (CH), 106.10
(CH), 105.49 (CH), 101.40 (CH), 21.08 (CH2), 14.01(CH3) ppm.
C10H11NO requires: C, 74.51; H, 6.88; N, 8.69%. Found: C, 74.73; H,
6.99; N, 8.48%.
3,5-Dimethyl-2-(5-methylthien-2-yl)-1H-pyrrole (2p)
2-Ethyl-5-(thien-2-yl)-1H-pyrrole (2l) [44]
Yellow oil, yield %. 1H NMR (400 MHz, CDCl3, 300 K): δ = 7.73 (br s,
exchangeable, 1H, NH), 6.74 (d, J = 3.5 Hz, 1H, Hthioph.), 6.70 (m, 1H,
Hthioph.), 5.80 (br s, 1H, Hpyrrole), 2.51 (s, 3H, CH3), 2.28 (s, 3H, CH3), 2.22
(s, 3H, CH3) ppm. 13C NMR (100 MHz, CDCl3, 300 K): δ = 136.86 (C),
134.14 (C), 127.60 (C), 125.79 (CH), 121.20 (CH), 119.90 (C), 116.56
(C), 110.10 (CH), 15.20 (CH3), 13.09 (CH3), 12.44 (CH3) ppm. C11H13NS
requires: C, 69.07; H, 6.85; N, 7.32%. Found: C, 69.38; H, 7.12; N,
7.11%.
Yellow oil, yield 48%. 1H NMR (400 MHz, CDCl3): δ = 8.01 (br s,
exchangeable, 1H, NH), 7.20 – 7.07 (m, 1H, Hthioph), 7.03-6.97 (m, 2H,
Hthioph), 6.43 (t, J = 3.0 Hz, 1H, Hpyrrole), 5.98 (t, J = 3.0 Hz, 1H, Hpyrrole),
2.69 (q, J = 7.6 Hz, 2H, CH2), 1.31 (t, J = 7.6 Hz, 3H, CH3) ppm. 13C
NMR (100 MHz, CDCl3): δ = 136.68 (C), 135.33 (C), 127.56 (CH), 125.17
(C), 122.02 (CH), 120.11 (CH), 106.81 (CH), 106.13 (CH), 20.93 (CH2),
13.58 (CH3) ppm. C10H11NS requires: C, 67.76; H, 6.25; N, 7.90%.
Found: C, 68.10; H, 6.50; N, 7.68%. Spectral data of the compound are
in accordance with those reported in the literature
(E)-2-(2-Nitroprop-1-en-1-yl)-1H-indole[51]
Yellow solid, yield 56%. 1H NMR (300 MHz, CDCl3, 300 K): δ = 8.37 (br s,
exchangeable, 1H, NH), 8.13 (s, 1H, alkenyl H), 7.71 (d, J = 8.0 Hz, 1H,
HAr), 7.45 (d, J = 8.2 Hz, 1H, HAr), 7.34 (t, J = 7,6 Hz, 1H, HAr), 7.20 (t, J =
7.6 Hz, 1H, HAr), 6.99 (s, 1H, Hpyrrole), 2.66 (s, 3H, CH3) ppm. Spectral
data of the compound are in accordance with those reported in the
literature.
3,5-Dimethyl-2-phenyl-1H-pyrrole (2m) [50]
Colorless oil, yield 52%.1H NMR (400 MHz, CDCl3, 300 K): δ = 7.83 (br s,
exchangeable, 1H, NH), 7.43 (s, 4H, HAr), 7.23 (m, 1H, HAr), 5.87 (s, 1H,
Hpyrrole), 2.33 (s, 3H, CH3), 2.28 (s, 3H, CH3) ppm. 13C NMR (101 MHz,
CDCl3, 300 K): δ = 133.90 (C), 128.65 (CH), 127.49 (C), 126.75 (C),
125.92 (CH), 125.46 (CH), 116.49 (C), 110.30 (CH), 12.98 (CH3), 12.49
(CH3) ppm. C12H13N requires: C, 84.17; H, 7.65; N, 8.18%. Found: C,
84.30; H, 7.55; N, 8.01%. Spectral data of the compound are in
accordance with those reported in the literature.
Acknowledgements
We acknowledge the Ministero dell’Università e della Ricerca
(MiUR) for financial support (PRIN 20154X9ATP). The authors
thank Prof. Dr. Alessandro Caselli for fruitful discussions and Mr.
Pasquale Illiano and Mr. Mario Rosa for excellent analytical
assistance. F.F. and M.E. thanks the University of Milano for a
postdoctoral fellowship.
5-Ethyl-3-methyl-2-phenyl-1H-pyrrole (2n) [44]
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10.1002/ejoc.201701814
European Journal of Organic Chemistry
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Keywords: C–H amination • Nitrogen heterocycles •
Nitroalkenes • Palladium • Carbonylation
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