Bis(pyrrol-2-yl)arylenes from the tandem bidirectional addition of vinyl grignard reagent to aryl diesters

Article abstract of DOI:10.1021/jo0510888

A practical three-step synthesis of bis(pyrrol-2-yl)arylenes has been accomplished, featuring a copper-catalyzed tandem bidirectional addition of vinylmagnesium bromide to aryldicarboxylates. Spectroscopic and cyclic voltammetric analyses revealed the inf

Full text of DOI:10.1021/jo0510888

Bis(pyrrol-2-yl)arylenes from the Tandem Bidirectional Addition
of Vinyl Grignard Reagent to Aryl Diesters
Karl A. Hansford, Sergio Andres Perez Guarin, W. G. Skene,* and William D. Lubell*
De´partement de Chimie, Universite´ de Montre´al, C.P. 6128, Succursale Centre Ville,
Montre´al, Que´bec, Canada H3C 3J7
lubell@chimie.umontreal.ca
Received May 31, 2005
A practical three-step synthesis of bis(pyrrol-2-yl)arylenes has been accomplished, featuring a
copper-catalyzed tandem bidirectional addition of vinylmagnesium bromide to aryldicarboxylates.
Spectroscopic and cyclic voltammetric analyses revealed the influence of the central aromatic core
and pyrrole substitution pattern on the electrochemical properties of these comonomers.
Introduction
monomer, and lead to more highly ordered polymers with
higher electrical conductivities in their doped form rela-
tive to their unsymmetrically substituted analogues.
Pyrrole-donor comonomers such as 1,4-bis(pyrrol-2-yl)-
benzene (1a) are particularly attractive because they are
more readily oxidized3 than their furan-donor and
thiophene-donor counterparts, providing electroactive
poly[1,4-bis(pyrrol-2-yl)arylene] polymers4 with polypyr-
role-like electrochromic properties that are useful for
biomedical applications.5
The synthesis of π-conjugated polymers is an intensive
area of research, owing to their unique properties and
commercial potential in a vast array of mechanical,
electrical, electrochemical, and optical applications.1
π-Conjugated polymers are typically prepared from the
electropolymerization of heterocyclic monomers; however,
polymer defects often arise from competing side reactions
such as overoxidation, â-coupling, and cross-linking, as
well as homopolymer formation due to mismatching of
monomer redox potentials. Monomers containing the
elements of the copolymer structure, so-called comono-
mers, have been employed to minimize such defects
leading to insoluble and infusible products and to provide
materials for accurate structure-property correlations.
Comonomers2 incorporating a central aromatic core (ac-
ceptor) sandwiched between electron-rich heterocycles
(donors) display high reactivity at the terminal positions,
have lower oxidation potentials relative to the parent
(2) (a) Soloducho, J.; Roszak, S.; Chyla, A.; Tajchert, K. New J.
Chem. 2001, 25, 1175-1181. (b) Tsuie, B.; Reddinger, J. L.; Sotzing,
G. A.; Soloducho, J.; Katritzky, A. R.; Reynolds, J. R. J. Mater. Chem.
1999, 9, 2189-2200. (c) Sotzing, G. A.; Reddinger, J. L.; Katritzky, A.
R.; Soloducho, J.; Musgrave, R.; Reynolds, J. R. Chem. Mater. 1997, 9,
1578-1587. (d) Geissler, U.; Hallensleben, M. L.; Rohde, N. Synth.
Met. 1997, 84, 173-174. (e) Pagani, G.; Berlin, A.; Canavesi, A.;
Schiavon, G.; Zecchin, S.; Zotti, G. Adv. Mater. 1996, 8, 819-823. (f)
Geissler, U.; Hallensleben, M. L.; Rohde, N. Macromol. Chem. Phys.
1996, 197, 2565-2576.
(3) Diaz, A. F.; Crowley, J.; Bargon, J.; Gardini, G. P.; Torrance, J.
B. J. Electroanal. Chem. 1981, 121, 355-361.
(4) (a) Larmat, F.; Soloducho, J.; Katritzky, A. R.; Reynolds, J. R.
Synth. Met. 2001, 124, 329-336. (b) Zotti, G.; Zecchin, S.; Schiavon,
G.; Berlin, A.; Pagani, G.; Borgonovo, M.; Lazzaroni, R. Chem. Mater.
1997, 9, 2876-2886. (c) Berlin, A.; Canavesi, A.; Pagani, G.; Schiavon,
G.; Zecchin, S.; Zotti, G. Synth. Met. 1997, 84, 451-452. (d) Sotzing,
G. A.; Reynolds, J. R.; Katritzky, A. R.; Soloducho, J.; Belyakov, S.;
Musgrave, R. Macromolecules 1996, 29, 1679-1684. (e) Reynolds, J.
R.; Katritzky, A. R.; Soloducho, J.; Belyakov, S.; Sotzing, G. A.; Pyo,
M. Macromolecules 1994, 27, 7225-7227.
(1) (a) Heeger, A. J. Angew. Chem., Int. Ed. 2001, 40, 2591-2611.
(b) Moliton, A.; Hiorns, R. C. Polym. Int. 2004, 53, 1397-1412. (c)
Roncali, J. Chem. Soc. Rev. 2005, 34, 483-495. (d) Shirota, Y. J. Mater.
Chem. 2000, 10, 1-25. (e) Shi, C.; Wu, Y.; Zeng, W.; Xie, Y.; Kaixia
Yang, Y. C. Macromol. Chem. Phys. 2005, 206, 1114-1125. (f) Morin,
J.-F.; Leclerc, M.; Ade`s, D.; Siove, A. Macromol. Rapid Commun. 2005,
26, 761-778.
10.1021/jo0510888 CCC: $30.25 © 2005 American Chemical Society
Published on Web 09/08/2005
7996
J. Org. Chem. 2005, 70, 7996-8000

Bis(pyrrol-2-yl)arylenes from Aryl Diesters
SCHEME 1. Synthesis of Bis(pyrrol-2-yl)arylenes 1a-ha
a Conditions: (a) vinylmagnesium bromide (6 equiv), CuCN (0.6 equiv), -78 to 0 °C; (b) (i) O3, CH2Cl2/MeOH, -78 °C, (ii) NaHCO3,
Me2S; (c) PdCl2, CuCl, O2, THF/H2O, ultrasound; (d) NH4CO2H or n-BuNH2, for conditions, see Experimental Section.
Practical synthetic strategies6 are desired which allow
for the ready incorporation of a variety of substituted
donor and acceptor subunits within the comonomer to
enable fine-tuning of the polymer band gap for optimal
conduction.7 Three strategies have been typically used
to construct bis(pyrrol-2-yl)arylenes 1: (a) construction
of the aromatic core from a flanked bispyrrole system,5a,8
(b) transition-metal-catalyzed attachment of preformed
pyrrole analogues to a suitably derivatized aromatic
core,2f,4b and (c) tandem pyrrole synthesis on the aromatic
core from linear precursors.2a-c,4d,e,9,10 Multiple steps,
relatively harsh conditions, and low yields have typically
limited bis(pyrrol-2-yl)arylene diversity with these ap-
proaches.
Recently, we described a practical protocol for synthe-
sizing homoallylic ketones by copper-catalyzed cascade
addition of vinyl Grignard reagent to carboxylic esters11a
and demonstrated its utility in a three-step synthesis of
substituted pyrroles.11b By applying this methodology in
a tandem fashion on aromatic diesters, we have now
developed a relatively concise synthesis of bis(pyrrol-2-
yl)arylenes (1). The influence of pyrrole regioalkylation
and the central aryl core on the spectroscopic and
electronic properties of 1a-h was determined using UV-
visible and fluorescence spectroscopy and cyclic voltam-
metry.
Results and Discussion
Bis(pyrrol-2-yl)arylenes 1a-h were prepared in three
steps from the corresponding aryldicarboxylates 2 by a
route featuring vinyl Grignard reagent addition, olefin
oxidation, and Paal-Knorr12 condensation (Scheme 1).
Aryldicarboxylates 2a-c were treated with freshly pre-
pared vinylmagnesium bromide (600 mol %) in the
presence of CuCN (60 mol %) at -78 °C, warmed to 0 °C
for 1 h, quenched at -78 °C with MeOH, and poured onto
a rapidly stirred biphasic mixture of aqueous NaH2PO4
and Et2O. After isolation and chromatography over silica
gel, bis-homoallylic ketones 3a-c were isolated in yields
of 59, 68, and 59%, respectively (Scheme 1). Bis-1,4-keto
aldehydes 4 were prepared by ozonolysis of 3 in CH2Cl2/
MeOH at -78 °C, followed by treatment with excess
dimethyl sulfide in the presence of NaHCO3.13 After
extractive workup, bis-1,4-keto aldehydes 4 were used
without further purification and stored for >6 months
under argon at 0 °C without decomposition. Bis-1,4-
diketones 5 were best obtained using a modification14 of
the Tsuji-Wacker15 protocol employing PdCl2 (0.4 equiv)
and CuCl (2 equiv) in THF/H2O (4:1) under an atmo-
sphere of oxygen with ultrasound agitation (Scheme 1).
After aqueous workup, the crude ketones were suf-
ficiently pure for subsequent use.16 Bis-homoallylic ke-
tone 3b failed to react under similar conditions,17a
presumably due to complexation with palladium, while
attempts using its trifluoroacetate led to decomposition.17b
Bis(pyrrol-2-yl)arylenes 1 were prepared by tandem
ring closure on 1,4-dicarbonyl compounds 4 and 5 using
different Paal-Knorr12 reaction conditions contingent
(5) (a) Rivers, T. J.; Hudson, T. W.; Schmidt, C. E. Adv. Funct. Mater.
2002, 12, 33-37. (b) Cui, X. Y.; Lee, V. A.; Raphael, Y.; Wiler, J. A.;
Hetke, J. F.; Anderson, D. J.; Martin, D. C. J. Biomed. Mater. Res.
2001, 56, 261-272. (c) Collier, J. H.; Camp, J. P.; Hudson, T. W.;
Schmidt, C. E. J. Biomed. Mater. Res. 2000, 50, 574-584.
(6) (a) Roncali, J. Chem. Rev. 1997, 97, 173-205. (b) van Mullekom,
H. A. M.; Vekemans, J. A. J. M.; Havinga, E. E.; Meijer, E. W. Mater.
Sci. Eng. R. 2001, 32, 1-40. (c) Havinga, E. E.; Hoeve, W.; Wynberg,
H. Polym. Bull. 1992, 29, 119-126.
(7) (a) Meyers, F.; Heeger, A. J.; Bredas, J. L. Synth. Met. 1993, 57,
4308-4313. (b) Meyers, F.; Heeger, A. J.; Bredas, J. L. J. Chem. Phys.
1992, 97, 2750-2758.
(8) Merrill, B. A.; Legoff, E. J. Org. Chem. 1990, 55, 2904-2908.
(9) Engel, E.; Steglich, W. Angew. Chem., Int. Ed. Engl. 1978, 17,
676.
(12) (a) Knorr, L. Chem. Ber. 1885, 18, 299. (b) Paal, C. Chem. Ber.
1885, 18, 367.
(13) Schreiber, S. L.; Claus, R. E.; Reagan, J. Tetrahedron Lett. 1982,
23, 3867-3870.
(14) Jie, M. S. F. L. K.; Lam, C. K. Chem. Phys. Lipids 1996, 81,
55-61.
(15) Tsuji, J. Synthesis 1984, 369-384.
(16) Crude products contained ca. 5% of the corresponding bis-1,4-
(10) Lucchesini, F. Tetrahedron 1992, 48, 9951-9966.
(11) (a) Hansford, K. A.; Dettwiler, J. E.; Lubell, W. D. Org. Lett.
2003, 5, 4887-4890. (b) Hansford, K. A.; Zanzarova, V.; Dorr, A.;
Lubell, W. D. J. Comb. Chem. 2004, 6, 893-898.
keto aldehyde by 1H NMR analysis.
(17) (a) PdCl2 (0.2 equiv), 1,4-benzoquinone (0.9 equiv), THF/H2O
(4:1), ultrasound, 90 min. (b) PdCl2 (0.4 equiv), CuCl (1 equiv), TFA (1
equiv), O2, DMF/H2O (7:1), 72 h.
J. Org. Chem, Vol. 70, No. 20, 2005 7997

Hansford et al.
TABLE 1. Cyclic Voltammetry Results of 1a-ha
TABLE 2. Spectroscopic Results of
Bis(pyrrol-2-yl)arylenes 1a-h
d
e
ꢀmax
(cm-1
∆λHOMO-LUMO
Eg
(eV/ kcal
mol-1
sam- λabs
λfl
τ
(ns)
(eV/kcal
ple (nm)a (nm)b Φc
M-1
)
mol-1
)
)
1a
1b
1c
1d
1e
1f
330
317
293
315
344
330
352
367
378 0.74 26 440 1.9
394 0.59 32 800 2.0
440 0.64 48 230 1.9
418 0.43 25 780 2.0
397 0.56 25 590 2.6
391 0.27 23 310 1.2
422 0.78 18 880 2.8
438 0.84 12 490 2.9
3.5/80.4
3.4/77.8
3.7/84.3
3.5/80.5
3.3/76.5
3.4/78.5
3.2/73.7
3.1/71.1
3.1/71.5
3.3/75.2
3.4/78.9
3.3/76.9
3.2/73.9
3.3/76.2
2.9/68.7
2.9/66.3
1g
1h
comonomerc
polymerc,d
1
2
1
sam- yield
Ep,a
Ep,a
∆E1
Ep,a
(mV)
a Absorption. b Fluorescence. c Quantum yield relative to bis-
(thiophene).21c d Absorption-emission intercept. e Spectroscopic
band gap.
ple
(%)b R1 R2
(mV)
(mV)
(mV)
1a 61 (36)
H
H
H
0 (644)
576 (1228) 576 -75 (569)
1b 59 (35) Me
-118 (496) 292 (771) 410
1c 63 (36)
H n-Bu 264 (851) 737 (1317) 473 146 (660)
their parent counterparts 1a,e, respectively, demon-
strated that pyrrole N-alkylation increased the oxidation
potential, making oxidative polymerization more difficult.
The smaller oxidation potential of analogue 1d, however,
indicated that the effect of N-alkylation was counterbal-
anced by C-5 alkylation. In all cases, smaller ∆E values
were observed relative to benchmark 1a, indicating that
N-alkylation decreased the overall stability of the
system20,21a (Table 1).
1d 65 (38) Me n-Bu 88 (692) 377 (1082) 289
1e 83 (46)
1f 68 (38)
1g 51 (24)
H
H
H
H
189 (792) 657 (1256) 468 378 (1022)
n-Bu 288 (875) 734 (1298) 446 1034 (1678)
H
H
-99 (316) 599 (813) 698 176 (820)
-172 (386) 25 (632) 197
1h 29 (17) Me
a Conditions: in deaerated anhydrous acetonitrile with 0.1 M
Bu4NPF6 measured against a saturated Ag/AgCl reference elec-
trode, silver working and platinum auxiliary electrodes, sweep rate
500 mV/s. The first and second anodic potentials are given.
b Isolated yield from 1,4-dicarbonyl precursor (yield over three
steps from starting diester in parentheses). c The oxidation po-
tentials are referenced to 1a, taken as 598 mV vs SCE by
referencing to ferrocene.21b Values in parentheses are relative to
Ag/AgCl. d Polymerization was achieved by repeated oxidation/
reduction cycles or continuous oxidation (ca. 5 min) at a potential
slightly more positive than the first oxidation peak (see the
Supporting Information).
The comonomer oxidation potential was also influenced
by the nature of the π-acceptor core. The electron-
deficient pyridine core destabilized the radical cation
product derived from comonomer 1e, as shown by the
increased anodic potential, making oxidation more dif-
ficult (Table 1). In contrast, incorporation of the electron-
rich thiophene moiety (analogue 1g) promoted both
monomer and polymer oxidation via a relatively more
stable radical cation intermediate, suggesting that this
analogue may be suitable for practical applications.
In the UV-visible spectra, 1a-h were observed to
undergo direct S0 f S1 absorption transitions (Table 2).
Both the absorption and fluorescence spectra of 1a-h
revealed structureless ground- and excited-state geom-
etries, suggesting free aryl-aryl bond rotation was the
major pathway for excited-state deactivation. This was
supported by the observed monoexponential fluorescence
decays. The quantum yields (Φ) exhibited by 1a-h were
found to be higher than most other related22 electronically
active compounds, indicating a limited number of avail-
able quenching pathways for excited deactivation (Table
2). The LUMO lowering influence of the pyridyl and
thiophenyl cores was reflected in the bathochromic shifts
displayed by 1e,g in their UV-visible spectra, respec-
tively, consistent with an enhanced degree of ground-
state stabilization.
upon the substitution pattern (Scheme 1, Table 1). For
example, N-butylpyrroles 1c,d,f were readily prepared
by condensation of the appropriate 1,4-dicarbonyl com-
pound with n-butylamine in the presence of a 1:1 mixture
of NaOAc/HOAc (1 equiv w/w) in toluene at 60-70 °C.18a
On the other hand, attempts to prepare 1a,e using NH4-
CO2H and similar conditions led to significant polymer-
ization. In this case, best results were obtained by
treating bis-1,4-keto aldehydes 4a,b with NH4CO2H and
KOAc in a HOAc/CH3CN/H2O mixture (1:1:1) at 60-70
°C under argon.18b For the formation of bis-pyrroles
1b,g,h, improved yields were obtained by treatment10 of
the respective 1,4-dicarbonyl compounds with NH4CO2H
in NH4OH/EtOH at 60-70 °C under argon.18c
The cyclic voltammograms of 1a-h exhibited two
sequential one-electron oxidations corresponding to a
radical cation followed by cation formation. The oxidative
process was irreversible even at fast sweep rates, indicat-
ing the formation of highly reactive intermediates.2a,4a,b,e,19
A comparison of the comonomer oxidation potentials of
1a,b revealed that alkylation at the 5-position facilitated
oxidation but inhibited both 4,4′- and 5,5′-electropolym-
erization, even at prolonged oxidation times, due to stable
radical cation formation20 (Table 1). To improve solubility
properties in acetonitrile, we examined the N-alkylated
analogues 1c,d,f. A comparison of analogues 1c,f versus
In summary, a series of bis-(pyrrol-2-yl)arylene comono-
mers was prepared by a practical three-step synthesis
featuring treatment of aromatic diesters with excess
vinylmagnesium bromide in the presence of CuCN in
THF. The spectroscopic and redox properties of this
comonomer series were examined by UV-visible and
(21) (a) Organic Electrochemistry, 4th ed.; Lund, H., Hammerich,
O., Eds.; Marcel Dekker: New York, 2001. (b) The value for ferrocene
was taken as 395 mV vs SCE in acetonitrile. See: Connolly, N. G.
Chem. Rev. 1996, 2, 877-910. (c) Seixas de Melo, J.; Elisei, F.; Gartner,
C.; Aloisi, G. G.; Becker, R. S. J. Phys. Chem. 2000, 104, 6907-6911.
(22) (a) Miyata, Y.; Nishinaga, T.; Komatsu, K. J. Org. Chem. 2005,
70, 1147-1153. (b) Mikroyannidis, J. A.; Spiliopoulos, I. K.; Kulkarni,
A. P.; Jenekhe, S. A. Synth. Met. 2004, 142, 113-120.
(18) (a) Purified by chromatography over silica gel. (b) Purified by
chromatography over Florisil. (c) Purified by trituration (1b) or
preparative TLC over silica gel (1g,h).
(19) Hong, S. Y.; Marynick, D. S.; Macromolecules 1992, 25, 3591-
3595.
(20) Audebert, P.; Catel, J.-M.; Le Coustumer, G.; Duchenet, V.;
Hapiot, P.; J. Phys. Chem. 1995, 99, 11923-11929.
7998 J. Org. Chem., Vol. 70, No. 20, 2005

Bis(pyrrol-2-yl)arylenes from Aryl Diesters
General Procedure for the Preparation of Bis-1,4-
diketones (5). A two-necked flask was fitted with a septum
and a three-way stopcock connected to an oxygen-filled balloon.
The flask was charged with PdCl2 (0.2 equiv) and CuCl (2
equiv), diluted with THF/H2O (4:1; 15 mL per 1 mmol of 3),
evacuated and flushed with oxygen three times. After it was
stirred at room temperature for 1 h, the mixture was treated
via syringe with a solution of 3 (1 equiv) in THF/H2O (4:1;
5 mL per 1 mmol of 3) and the reaction flask was then
immersed in an ultrasound bath. After sonication for 90 min
the reaction mixture was treated with PdCl2 (0.2 equiv) and
sonication was continued for 90 min. The resultant mixture
was diluted with a small quantity of EtOAc, transferred to a
separatory funnel, and agitated with a solution of 28% NH4-
OH/brine (10:90). The phases were separated, and the aqueous
phase was extracted with EtOAc. The pooled extracts were
washed with a solution of pH 6.7 sodium phosphate buffer/
brine (1:1), dried, filtered, and evaporated to yield 5, which
was used without further purification.
fluorescence spectroscopy and cyclic voltammetry to
determine the influences of pyrrole alkylation and modi-
fication of the central aromatic core. Oxidation potentials
were lowered by C-5-alkylation and raised by N-alkyla-
tion. The thiophene core unit had the most desired effect
by lowering both monomer and polymer oxidation poten-
tials. This methodology should thus be of general use for
synthesizing a variety of substituted donor-acceptor
comonomers for the preparation of π-conjugated poly-
mers.
Experimental Section
General Procedure for the Preparation of Bis-Homo-
allylic Ketones (3). A teflon coated magnetic stirrer bar and
CuCN (0.6 equiv) were placed in a two-neck round-bottom flask
fitted with a septum and gas inlet. The flask and contents were
briefly flame-dried under a stream of argon and then cooled
to room temperature. The flask was briefly opened, and diester
2 (1.0 equiv) was added. The reaction mixture was diluted with
a quantity of THF, cooled to -78 °C, and treated with a so-
lution of freshly prepared vinylmagnesium bromide in THF
(6.0 equiv) over 15 min, giving a final concentration of ca. 0.15
M in 2. After rapid stirring for 1 h at -78 °C, the cooling bath
was replaced with an ice bath and stirring was continued for
1 h. The resultant dark slurry was recooled to -78 °C, treated
with the specified volume of MeOH, and poured onto a rapidly
stirred biphasic solution of ice-chilled 2 M NaH2PO4 and Et2O.
After ca. 1 h, the color disappeared, a white precipitate formed,
and the mixture was treated with the specified volume of 3 M
HCl solution. The phases were separated, and the aqueous
phase was extracted with EtOAc. The pooled extracts were
washed with brine, dried, filtered, and evaporated to give the
corresponding bis-homoallylic ketone 3, which was purified by
flash chromatography over silica gel (eluant: toluene or
toluene/Et2O).
1-(6-Pent-4-enoyl-pyridin-3-yl)pent-4-en-1-one (3b): yield
68% from 2b; 1H NMR (400 MHz, CDCl3) δ 2.43-2.55 (m, 4H),
3.10 (t, J ) 7.3 Hz, 2H), 3.33 (t, J ) 7.3 Hz, 2H), 4.95-5.04
(m, total width between outside lines 26.8 Hz, 2H) partly
overlapped with 5.04-5.12 (m, total width between outside
lines 23.4 Hz, 2H), 5.81-5.94 (m, 2H), 8.09 (d, J ) 8.2 Hz,
1H), 8.31 (dd, J ) 8.2, 2.1 Hz, 1H), 9.17 (br d, J ≈ 2 Hz, 1H);
13C NMR (100 MHz, CDCl3) δ 27.7, 27.8, 37.1, 38.4, 115.2,
115.8, 121.6, 134.1, 136.3, 136.5, 137.1, 148.8, 155.5, 197.7,
200.5; HRMS (ESI) calcd for C15H17NO2 [M + H+] 244.1332,
found 244.1339.
General Procedure for the Preparation of Bis-1,4-keto
Aldehydes (4). A solution of 3 (1 equiv) in the specified
MeOH/CH2Cl2 mixture was treated with ozone at -78 °C until
a blue color persisted. The -78 °C reaction mixture was purged
with a stream of argon to remove excess ozone and then
treated successively with solid NaHCO3 (8 equiv) and dimethyl
sulfide (10 equiv). Stirring was continued overnight, after
which time the bath temperature had warmed to room
temperature. The solvent was removed by rotary evaporation,
and the residue was partitioned between CH2Cl2 and H2O. The
phases were separated, and the aqueous phase was extracted
with CH2Cl2. The pooled extracts were dried, filtered, and
evaporated to yield 4, which was used without further puri-
fication and stored under argon at 0 °C for >6 months without
decomposition.
4-Oxo-4-[6-(4-oxobutyryl)-pyridin-3-yl]butyraldehyde
(4b): prepared from 3b in MeOH/CH2Cl2 (1:3); crude yield 82%
from 3b; 1H NMR (400 MHz, CDCl3) δ 2.91 (t, J ) 6.3 Hz,
2H), 2.97 (t, J ) 6.1 Hz, 2H), 3.31 (t, J ) 6.1 Hz, 2H), 3.54 (t,
J ) 6.3 Hz, 2H), 8.08 (d, J ) 8.1 Hz, 1H), 8.33 (dd, J ) 8.1,
2.1 Hz, 1H), 9.20 (br d, J ≈ 2 Hz, 1H), 9.85, 9.86 (two partly
overlapped s, total area 2H); 13C NMR (100 MHz, CDCl3) δ
30.7, 31.4, 37.3, 37.6, 121.6, 133.9, 136.4, 148.8, 155.2, 196.3,
198.9, 199.8, 200.4; HRMS (ESI) calcd for C13H13NO4 [M +
H+] 248.0917, found 248.0918.
1-[4-(4-Oxopentanoyl)phenyl]pentane-1,4-dione (5a):
crude yield 74% from 3a; mp 152-153 °C; 1H NMR (400 MHz,
CDCl3) δ 2.23 (s, 6H), 2.88 (t, J ) 6.2 Hz, 4H), 3.25 (t, J ) 6.2
Hz, 4H), 8.01 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 30.0, 32.7,
36.9, 128.2, 139.7, 198.0, 207.0; HRMS (ESI) calcd for C16H18O4
[M + H+] 275.1278, found 275.1279.
General Procedure for the Preparation of Pyrroles
(1a,e). A stock solution was prepared containing KOAc (∼0.7
g, ∼7 mmol) and HOAc (∼0.5 mL, ∼8 mmol) in CH3CN (0.5
mL) and H2O (0.5 mL). In a round-bottom flask a mixture of
bis-1,4-keto aldehyde 4a or 4b (100 mol %) and ammonium
formate (1000 mol %) was suspended in a quantity of the stock
solution (10 mL per 1 mmol of 4). The reaction flask was
evacuated and flushed with argon three times, and the
contents were heated to 60-70 °C with stirring. After it was
cooled to room temperature, the reaction mixture was parti-
tioned between saturated NaHCO3 solution and EtOAc. The
phases were separated, and the aqueous phase was extracted
with EtOAc. The pooled extracts were washed with brine,
dried, filtered, and evaporated to afford the corresponding
pyrrole. The resulting pyrroles were purified by a successive
sequence of chromatography over Florisil (eluant: CHCl3 or
CHCl3/acetone) and trituration (1:1 Et2O/pentane).
2,5-Bis(1H-pyrrol-2-yl)pyridine (1e): yield 83% from 4b;
mp 281-286 °C dec; 1H NMR (400 MHz, d6-acetone) δ 6.21
(dt, J ) 5.9, 2.6 Hz, 2H), 6.92-6.96 (m, 2H), 6.73-6.76 (m,
1H), 6.60-6.63 (m, 1H), 7.65 (dd, J ) 8.4, 0.6 Hz, 1H), 7.93
(dd, J ) 8.4, 2.4 Hz, 1H), 8.78 (m, 1H), 10.52-10.84 (br s, 2H);
13C NMR (100 MHz, d6-acetone) δ 106.9, 107.8, 110.3, 110.4,
118.5, 120.5, 120.9, 126.7, 129.6, 131.9, 132.4, 145.0, 149.1;
HRMS (ESI) calcd for C13H12N3 [M + H+] 210.1026, found
210.1031.
General Procedure for the Preparation of Pyrroles
(1c,d,f). A mixture of 1,4-dione 4a or 5a (100 mol %),
n-butylamine (400 mol %), and NaOAc/HOAc (prepared by
mixing equimolar quantities of NaOAc and HOAc; 1 equiv w/w)
in toluene (10 mL per 1 mmol of 1,4-dione) was heated to 60-
70 °C with stirring. After it was cooled to room temperature,
the reaction mixture was partitioned between Et2O/CH2Cl2 (2:
1) and aqueous HCl solution (1 M). The phases were separated,
and the aqueous phase was extracted with Et2O/CH2Cl2 (2:1).
The pooled extracts were washed with pH 6.8 phosphate
buffer, dried, filtered, and evaporated to afford the correspond-
ing pyrrole. The resulting pyrroles were purified by chroma-
tography over silica gel (eluant: toluene).
1-Butyl-2-[4-(1-butyl-1H-pyrrol-2-yl)phenyl]-1H-pyr-
role (1c): yield 63% from 4a; mp 72-74 °C; 1H NMR (400
MHz, d6-acetone) δ 0.80 (t, J ) 7.4 Hz, 6H), 1.14-1.25 (m,
4H), 1.57-1.66 (m, 4H), 4.04 (t, J ) 7.3 Hz, 4H), 6.11 (t, J )
3.1 Hz, 2H), 6.15 (dd, J ) 3.5, 1.8 Hz, 2H), 6.85 (t, J ) 2.4 Hz,
2H), 7.44 (s, 4H); 13C NMR (100 MHz, d6-acetone) δ 13.8, 20.3,
34.2, 47.5, 108.5, 109.5, 123.4, 129.3, 133.1, 134.3; HRMS (ESI)
calcd for C22H29N2 [M + H+] 321.2325, found 321.2327.
J. Org. Chem, Vol. 70, No. 20, 2005 7999

Hansford et al.
General Procedure for the Preparation of Pyrroles
(1b,g,h). A mixture of 1,4-dione 4c, 5a, or 5c (100 mol %) and
ammonium formate (1000 mol %) was suspended in a solution
of 28% NH4OH/EtOH (1:25; 30 mL per 1 mmol of 1,4-dione).
The reaction flask was evacuated and flushed with argon three
times, and the contents were heated to 60-70 °C with stirring.
After it was cooled to room temperature, the reaction mixture
was partitioned between EtOAc and brine. The phases were
separated, and the aqueous phase was extracted with EtOAc.
The pooled extracts were dried, filtered, and evaporated to
afford the corresponding pyrrole. Pyrrole 1b was purified by
trituration (1:1 MeOH/pentane). Pyrroles 1g,h were purified
by a successive sequence of preparative TLC (eluant: 60:40
petroleum ether/Et2O or 30:70 Et2O/CHCl3, respectively) fol-
lowed by trituration (1:1 Et2O/pentane).
(dd, J ) 2.6, 1.4 Hz, 2H), 6.98 (s, 2H); 13C NMR (100 MHz,
d4-MeOH) δ 106.6, 109.9, 119.5, 121.5, 127.8, 134.8; HRMS
(ESI) calcd for C12H11N2S [M + H+] 215.0637, found 215.0632.
Acknowledgment. We acknowledge financial sup-
port from the NSERC of Canada, the FQRNT, and
equipment made possible from the Canada Foundation
for Innovation.
Supporting Information Available: Text giving detailed
1
experimental procedures and figures giving H and 13C NMR
spectra of all compounds, absorption and fluorescence spectra
of 1a-h, and cyclic voltammograms of 1a-h and of the
corresponding polymers derived from 1a,c,e-g. This material
is available free of charge via the Internet at http://pubs.acs.org.
2,5-Bis(1H-pyrrol-2-yl)thiophene (1g): yield 51% from
4c; mp 197-207 °C dec; 1H NMR (400 MHz, d4-MeOH) δ 6.13
(dd, J ) 3.3, 2.9 Hz, 2H), 6.28 (dd, J ) 3.4, 1.4 Hz, 2H), 6.77
JO0510888
8000 J. Org. Chem., Vol. 70, No. 20, 2005