First synthesis of a conformationally restricted 2,2′-bipyrrole

Article abstract of DOI:10.1055/s-2002-19305

A seven-step procedure was developed for the preparation of the cyclooctadiene-annulated 2,2′-bipyrrole 14, starting from commercially available benzyl bromoacetate 6 and adiponitrile 7. Although all transformations carried out had to be sufficiently selective to produce the desired functionalities on both sites of the respective dipyrroles, acceptable to good yields were observed throughout the synthesis. The paper reports synthetic and spectroscopic details of the new compounds.

Full text of DOI:10.1055/s-2002-19305

PAPER
67
First Synthesis of a Conformationally Restricted 2,2’-Bipyrrole
Synthesis of
a
Conform
a
ationally R
r
estricted
t
2,2’-B
i
ipyrro
n
Institut für Anorganische Chemie, Universität Würzburg, Am Hubland, 97074 Würzburg, Germany
Fax +49(931)8884605; E-mail: Martin.Broering@mail.uni-wuerzburg.de
Received 17 September 2001; revised 23 October 2001
ligand binding strength is too low to balance the tension
induced by the helical twist of complexes 1, with the con-
sequence, that only a limited set of porphyrin-like metal-
lo-2,2’-bidipyrrins is available. To overcome these
Abstract: A seven-step procedure was developed for the prepara-
tion of the cyclooctadiene-annulated 2,2’-bipyrrole 14, starting
from commercially available benzyl bromoacetate 6 and adiponi-
trile 7. Although all transformations carried out had to be sufficient-
ly selective to produce the desired functionalities on both sites of the limitations we sought to prepare a conformationally re-
respective dipyrroles, acceptable to good yields were observed
stricted 2,2’-bidipyrrin, in which the ligand framework
throughout the synthesis. The paper reports synthetic and spectro-
ensures a complex geometry of the ML type.
scopic details of the new compounds.
Key words: 2,2’-bipyrroles, pyrroles, conformation, heterocycles,
ring closure
N
N
Zn
N
N
2,2’-Bipyrroles are long-known compounds found in na-
ture as structural subunits of the antibiotical, antimalarial,
cytotoxic, and immunosuppressive active prodigiosins.1
Although not suited for the synthesis of porphyrins due to
the direct pyrrole–pyrrole linkage, quite a number of por-
phyrinoid macrocycles2 and open-chain oligopyrroles3
were prepared in the past from these simple building
blocks. The accessibility of -alkyl substituted 2,2’-bipyr-
roles, for a long time the major limiting factor in their
chemistry, was greatly improved in 1994 by Sessler et al.,4
and ever since the number of reports dealing with the use
of 2,2’-bipyrroles as precursors – mainly for macrocyclic
oligopyrroles – has constantly increased. In the light of
conducting polymers, 2,2’-bipyrroles can be regarded as
the smallest oligomeric fragment of polypyrrole. Several
applications based on the advantageous material proper-
ties of oligo- and polypyrroles including supercapacitors,
electrochemical sensors, anti-static coating and drug de-
livery systems have been described,5 and a recent publica-
tion discusses the luminescence properties of 2,2’-
bipyrroles in the solid state, based on the molecular con-
formation.6
N
N
Ni
N
N
N
N
Zn
N
N
1
2
Figure Chemical structures of ML complex 1 and M2L2 complex 2
A literature survey on the conformationally restricted bi-
pyrroles revealed only derivatives of benzo[2,1-b:3,4-
b’]bipyrrole,10 from which 3 was chosen for a test reac-
tion. Indeed, the HBr induced double condensation of 3
with two equivalents of 3,4-diethyl-2-methylpyrrole (5)
gave a dark-green powder (Scheme 1). This compound,
however, was found to be a tripyrrolic prodigiosin deriv-
ative rather than the anticipated 2,2’-bidipyrrin 4. Most
probably, the annulated benzene ring induces a pro-
nounced indole-like character in 3, which inhibits the dou-
ble condensation with pyrrole 5. To enable sufficient
reactivity, a (CH2)n-bridged 2,2’-bipyrrole with n = 3–5
should be more suitable. Here we report on our recent suc-
cess in synthesizing the required 2,2’-bipyrrol 14 with
n = 4.
In the course of studies towards the coordination chemis-
try of the open-chain tetrapyrrolic ligand 2,2’-bidipyrrin7
it was recently found, that due to the free rotation around
the central bipyrrolic bond mainly two different complex
geometries are observed. Besides the porphyrin analogous
ML (metal–ligand) complexes of, e.g. Ni(II) and others as
depicted in 1,8 the binding of two metal centers like Zn(II)
through the cooperative action of two ligands yields M2L2
compounds of structure 2,9 depending on the metal ion in-
volved (Figure). It appears likely, that the latter coordina-
tion type is observed in those cases, where the metal–
t-Bu
t-Bu
t-Bu
, -2 H2O
t-Bu
+
N
H
5
N
H
N
H
OHC
CHO
N
H
N
H
∆ in HBr, MeOH
N
N
3
4
Synthesis 2002, No. 1, 28 12 2001. Article Identifier:
1437-210X,E;2002,0,01,0067,0070,ftx,en;T09101SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881
Scheme 1

68
M. Bröring, S. Link
PAPER
The synthesis of 14, starting from commercially available employed in this reaction (acetic acid or diethyl ether),
benzyl bromoacetate 6 and adiponitrile (7), makes use of only low yields were observed due to a surprisingly non-
well-known transformations in pyrrole chemistry, which selective chlorination of - and -situated alkyl groups.
were optimized mainly due to the poor solubility of the Hydrogenolytic debenzylation to 12 (92% yield) and de-
new intermediates 8–12 (Scheme 2). A double Blaise re- carboxylative iodination using iodine monochloride in
action of 6 and 7 using Zinc/Copper couple in boiling THF gave the diiodide 13 in 65% yield, which was finally
THF results in the di- -keto ester 8 as a colorless solid in coupled intramolecularly to the desired 2,2’-bipyrrole 14
37% yield. Compound 8 and acetylacetone were then used by copper powder in 87% yield, using a protocol recently
in a Knorr synthesis to produce the dipyrrolic 1,4-di(4- developed for this purpose.4 No intermolecular Ullmann
acetyl-2-benzyloxycarbonyl-5-methyl-3-pyrrolyl)butane
coupling leading to oligomeric or macrocyclic material
(9) (29% yield), which was reduced to the diethyl deriva- was observed.
tive 10 with diborane, produced in situ from boron triflu-
With respect to a different strategy known for the synthe-
oride diethyl etherate and sodium borohydride, in 92%
yield.
sis of dipyrroles with -(CH2)n joints like 9–13, i.e. a dou-
ble acylation sequence starting from -free pyrroles and
the respective alkane , -diacid dichlorides,11 the novel
route described here circumvents the problems arising
from intramolecular ring closure reactions during the acy-
lation processes, and therefore requires less steps.
NC
O
(1) Zn/Cu, THF
(2) HCl/H2O
BnO
2
+
OBn
(37%)
O
O
Br
2
7
8
6
CN
NMR spectra were obtained with a Bruker AMX 400 spectrometer.
Chemical shifts ( ) are given in ppm relative to TMS. Mass spectra
were recorded on a Finnigan 90 MAT instrument. m/z values are
given for the most abundant isotopes only. Melting points were
measured by DSC on a Thermoanalyzer DuPont 9000. Elemental
analyses (C,H,N) were performed at the microanalytical laboratory
of the Institut für Anorganische Chemie, Universität Würzburg.
4,4’-Di-tert-butyl-5,5’-diformylbenzo[2,1-b:3,4-b’]bipyrrole (3)10
and 3,4-diethyl-2-methylpyrrole (5)12 were prepared as previously
described.
(1) NaNO2, THF, HOAc,
H2O
(2) Zn, NaOAc, acac
(29%)
BnO2C
HN
BnO2C
(1) NaBH4, BF3*Et2O,
THF
HN
(2) HOAc/H2O
(92%)
2
O
2
10
9
Dibenzyl 3,8-Dioxodecandioate (8)
Cu(OAc)2 H2O (6.4 g, 3.17 mmol) was suspended in glacial AcOH
(180 mL) and stirred for 5 min. Zinc powder (60 ; 58.8 g, 1.11 mol)
was added with vigorous stirring, and the suspension was stirred un-
til decolorization (about 1 min). The mixture was quickly filtered by
suction, the solids were washed successively with MeOH and Et2O,
then transferred into an argon-filled 1 L 3-neck round bottom flask,
equipped with a mechanical stirrer, reflux condenser, and dropping
funnel. The zinc/copper couple was suspended in anhyd THF (180
mL) and adiponitrile (7; 37.8 mL, 332 mmol) and refluxed under
N2. Heating was discontinued, and benzyl bromoacetate 6 (105.6
mL, 664 mmol) was added dropwise in a manner such that constant
boiling was maintained (about 30 min). After the addition, the re-
sulting slurry was refluxed for another 2 h, then cooled in an ice bath
and poured onto a mixture of crushed ice (90 g) and concd HCl (90
mL). After addition of further ice (90 g), the solids were filtered off,
the phases of the filtrate were separated and the aqueous layer was
washed with EtOAc (3 100 mL). All organic layers were com-
bined and evaporated at reduced pressure to leave a yellowish oil,
which crystallized upon addition of MeOH (100 mL). After filtra-
tion and excessive washing with MeOH, the title compound was ob-
tained as a colorless powder (50.4 g, 37%); mp 70 °C.
(1) SO2Cl2, CH2Cl2
(2) EtOH 98%
(74%)
BnO2C
HN
HO2C
HN
Pd/C, H2, THF
(92%)
EtO2C
EtO2C
2
2
12
11
ICl, NaOAc,
THF
(65%)
(1) Boc2O, DMAP,
CH2Cl2
(2) Cu, toluene
(3) 220°C
I
HN
EtO2C
N
H
N
(87%)
H
EtO2C
CO2Et
2
13
14
1H NMR (400 MHz, CDCl3): = 1.53 (m, 4 H, H-5,6), 2.47 (m, 4
H, H-4,7), 3.45 (s, 4 H, H-2,9), 5.16 (s, 4 H, CH2Ph), 7.35 (m, 10 H,
C6H5).
13C NMR (100.6 MHz, CDCl3): = 22.5 (C-5,6), 42.6 (C-4,7), 49.2
(C-2,9), 67.1 (CH2Ph), 128.4, 128.5, 128.6 (CHPh), 135.2 (Cipso),
167.0 (C-1,10), 202.1 (C-3,8).
Scheme 2
To set up this dipyrrole for the Ullmann coupling reaction,
a proper regiochemical arrangement of the pyrrolic 2- and
5-positions was achieved by selectively oxidizing the 5-
situated methyl groups with sulfuryl chloride in dichlo-
romethane and by concomitant hydrolysis/alcoholysis to
the tetraester 11 in 74% yield. If standard solvents were
MS (DCI, i-butane): m/z = 411 ([M + 1]+).
Anal. Calcd for C24H26O6: C, 70.23; H, 6.38. Found: C, 69.85; H,
6.11.
Synthesis 2002, No. 1, 67–70 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of a Conformationally Restricted 2,2’-Bipyrrole
69
1,4-Bis(4-acetyl-2-benzyloxycarbonyl-5-methyl-3-pyrrolyl)bu-
tane (9)
reduced pressure at r.t. The resulting red solid was treated with 98%
EtOH (240 mL), the mixture heated to reflux for 2 h and then al-
lowed to cool slowly to r.t. The product crystallized on cooling, and
was collected by suction filtration, washed with EtOH and dried at
60 °C to yield a colorless solid (43.1 g, 74%); mp 106 °C.
1H NMR (400 MHz, C6D6): = 0.88 (t, J = 7.4 Hz, 6 H, CH3CH2O),
1.24 (t, J = 7.4 Hz, 6 H, CH3CH2pyr), 1.78 (br s, 4 H, CH2CH2pyr),
2.85 (q, J = 7.4 Hz, 4 H, CH3CH2pyr), 2.89 (br s, 4 H, CH2CH2pyr),
3.97 (q, J = 7.4 Hz, 4 H, CH3CH2O), 5.08 (s, 4 H, CH2Ph), 7.00–
7.19 (m, 10 H, C6H5), 9.49 (br s, 2 H, NH).
13C NMR (100.6 MHz, C6D6): = 14.2 (CH3CH2O), 16.0
(CH3CH2pyr), 18.3 (CH3CH2pyr), 24.8 (CH2CH2pyr), 32.0
(CH2CH2pyr), 60.3 (CH3CH2O), 66.3 (CH2Ph), 121.5 (C-2), 122.0
(C-5), 128.4, 128.7, 128.8 (CHPh), 132.1 (C-3), 133.6 (C-4), 136.4
(C-Phipso), 160.4 (CO2Et), 160.5 (CO2Bn).
To a solution of 8 (100 g, 244 mmol) in THF (450 mL) was added
AcOH (500 mL). The solution was stirred and kept at r.t. by the aid
of a water bath, while a solution of NaNO2 (33.6 g, 487 mmol) in
H2O (100 mL) was added dropwise over a period of 2 h. The result-
ing mixture was stirred at r.t. for another hour before acetylacetone
(57.6 mL, 560 mmol) and AcOH (500 mL) were added. This solu-
tion was then heated to 80 °C and treated with a mixture of zinc
powder (65.4 g, 1 mol) and NaOAc (99.9 g, 1.22 mol) in small por-
tions to avoid a too vigorous reaction. After the addition was com-
plete, the slurry was heated to 100–110 °C for 2 h, stirred at r.t. for
another 12 h, filtered, and the cake washed carefully with MeOH.
The precipitate was again suspended in MeOH (500 mL), H2O (500
mL) was added to this suspension, and the product was again fil-
tered and washed with MeOH. Drying at 60 °C yielded pure product
as a colorless powder (40.2 g, 29%); mp 230 °C.
MS (EI, 70 eV): m/z = 656 (M+).
1H NMR (400 MHz, DMSO-d6): = 1.40 (br s, 4 H, CH2CH2pyr),
2.31 (s, 6 H, CH3CO), 2.45 (s, 6 H, CH3pyr), 2.93 (br s, 4 H,
CH2CH2pyr), 5.24 (s, 4 H, CH2Ph), 7.25–7.40 (m, 10 H, C6H5),
11.86 (br s, 2 H, NH).
13C NMR (100.6 MHz, DMSO-d6): = 14.7 (CH3pyr), 25.2
(CH2CH2pyr), 31.2 (CH3CO), 31.4 (CH2CH2pyr), 65.2 (CH2Ph),
117.0 (C-2), 122.1 (C-4), 128.0, 128.1, 128.6 (CHPh), 135.1 (C-3),
136.6 (C-Phipso), 139.3 (C-5), 160.7 (CO2Bn), 194.3 (COCH3).
Anal. Calcd for C38H44N2O8: C, 69.49; H, 6.75; N, 4.27. Found: C,
69.26; H, 6.73; N, 4.26.
1,4-Bis(2-carboxy-5-ethoxycarbonyl-4-ethyl-3-pyrrolyl)butane
(12)
To a solution of 11 (63.2 g, 96.1 mmol) in anhyd THF (800 mL) was
added Pd/C (10%, 7.0 g), and the mixture was hydrogenated at at-
mospheric pressure and r.t. for 12 h. The mixture was filtered and
the dark precipitate was carefully extracted with several small por-
tions of THF at 60 °C (1000 mL in total). After evaporation of the
solvent, the title compounds remained as a clean white solid (42.1
g, 92%); mp 253 °C.
MS (EI, 70 eV): m/z = 568 (M+).
Anal. Calcd for C34H36N2O6: C, 71.81; H, 6.38; N, 4.93. Found: C,
71.54; H, 6.29; N, 4.80.
1H NMR (400 MHz, DMSO-d6): = 1.01 (t, J = 7.4 Hz, 6 H,
CH3CH2pyr), 1.27 (t, J = 7.4 Hz, 6 H, CH3CH2O), 1.46 (br s, 4 H,
CH2CH2pyr), 2.60 (q, J = 7.4 Hz, 4 H, CH3CH2pyr), 2.66 (br s, 4 H,
CH2CH2pyr), 4.21 (q, J = 7.4 Hz, 4 H, CH3CH2O), 11.31 (br s, 2 H,
NH), 12.7 (br s, 2 H, CO2H).
13C NMR (100.6 MHz, DMSO-d6): = 14.4 (CH3CH2O), 16.0
(CH3CH2pyr), 17.6 (CH3CH2pyr), 24.0 (CH2CH2pyr), 31.4
(CH2CH2pyr), 60.1 (CH3CH2O), 121.1 (C-5), 122.6 (C-2), 130.2
(C-3), 132.5 (C-4), 160.4 (CO2Et), 162.1 (CO2H).
1,4-Bis(2-benzyloxycarbonyl-4-ethyl-5-methyl-3-pyrrolyl)bu-
tane (10)
In a 2 L 3-neck round bottom flask, equipped with an efficient me-
chanical stirrer, thermometer, and dropping funnel, 1,4-di(4-acetyl-
2-benzyloxycarbonyl-5-methyl-3-pyrrolyl)butane (9; 93.2 g, 164
mmol) and NaBH4 (22.7 g, 601 mmol) were suspended in anhyd
THF (500 mL) under a blanket of argon, and cooled in an ice bath.
BF3 OEt2 (103 mL, 820 mmol) was added dropwise at such a rate as
to maintain the temperature at or below 5 °C (about 1 h). After the
addition, the mixture was warmed to r.t. and stirred for an additional
hour. The mixture was cooled to 10 °C and hydrolized carefully
with AcOH (110 mL), and then with H2O (620 mL) maintaining the
temperature below 15 °C. The resulting slurry was stirred at r.t.
overnight, then filtered by suction and the precipitated product care-
fully washed with H2O. Drying at 60 °C yielded the title compound
as a colorless powder (81.5 g, 92%); mp 188 °C.
1H NMR (400 MHz, DMSO-d6): = 0.92 (t, J = 7.4 Hz, 6 H,
CH3CH2), 1.38 (br s, 4 H, CH2CH2pyr), 2.10 (s, 6 H, CH3pyr), 2.23
(q, J = 7.4 Hz, 4 H, CH3CH2), 2.55 (br s, 4 H, CH2CH2pyr), 5.18 (s,
4 H, CH2Ph), 7.25–7.38 (m, 10 H, C6H5), 11.07 (br s, 2 H, NH).
13C NMR (100.6 MHz, DMSO-d6): = 11.0 (CH3pyr), 16.1
(CH3CH2), 16.8 (CH3CH2), 24.9 (CH2CH2pyr), 31.7 (CH2CH2pyr),
64.4 (CH2Ph), 115.0 (C-2), 122.4 (C-4), 127.9, 128.0, 128.5 (CHPh),
130.7 (C-5), 131.5 (C-3), 137.2 (C-Phipso), 160.6 (CO2Bn).
MS (EI, 70 eV): m/z = 476 (M+).
Anal. Calcd for C24H32N2O8: C, 60.49; H, 6.77; N, 5.88. Found: C,
60.41; H, 6.81; N, 5.74.
1,4-Bis(5-ethoxycarbonyl-4-ethyl-2-iodo-3-pyrrolyl)butane (13)
Compound 12 (20.0 g, 42.0 mmol) and NaOAc (20.6 g, 252 mmol)
were suspended in anhyd THF (400 mL) and heated under a blanket
of argon to 70 °C. The resulting suspension was treated dropwise
with a solution of ICl (26.6 g, 164 mmol) in anhyd THF (200 mL),
whereupon an almost clear, dark brown solution was formed. This
solution was stirred at 70 °C for 24 h, then cooled to r.t. and decol-
orized by the addition of aq Na2S2O3. The contents of the flask were
extracted with CH2Cl2 (3 200 mL), the combined organic layers
dried (Na2SO4) and evaporated to leave a brownish-yellow solid.
The solid was dissolved in cold EtOH (100 mL), stirred for 10 min,
filtered under suction, and the product was washed with EtOH until
colorless (17.5 g, 65%); mp 187 °C (dec.).
MS (EI, 70 eV): m/z = 540 (M+).
Anal. Calcd for C34H40N2O4: C, 75.53; H, 7.46; N, 5.18. Found: C,
74.94; H, 7.54; N, 5.07.
1H NMR (400 MHz, CDCl3): = 1.10 (t, J = 7.4 Hz, 6 H,
CH3CH2pyr), 1.33 (t, J = 7.4 Hz, 6 H, CH3CH2O), 1.49 (br s, 4 H,
CH2CH2pyr), 2.37 (br s, 4 H, CH2CH2pyr), 2.72 (q, J = 7.4 Hz, 4 H,
CH3CH2pyr), 4.30 (q, J = 7.4 Hz, 4 H, CH3CH2O), 8.90 (br s, 2 H,
NH).
13C NMR (100.6 MHz, CDCl3): = 14.4 (CH3CH2O), 15.6
(CH3CH2pyr), 18.8 (CH3CH2pyr), 26.3 (CH2CH2pyr), 30.6
(CH2CH2pyr), 60.1 (CH3CH2O), 73.2 (C-2), 123.2 (C-5), 129.8 (C-
3), 133.3 (C-4), 160.4 (CO2Et).
1,4-Bis(2-benzyloxycarbonyl-5-ethoxycarbonyl-4-ethyl-3-
pyrrolyl)butane (11)
Under a blanket of argon, compound 10 (48.0 g, 88.8 mmol) was
suspended in anhyd CH2Cl2 (240 mL), and SO2Cl2 (43.3 mL, 533
mmol) was slowly added while keeping the contents of the flask at
r.t. by the aid of a water bath. After the addition, the solution was
kept at r.t. for another 4 h before all volatiles were evaporated under
Synthesis 2002, No. 1, 67–70 ISSN 0039-7881 © Thieme Stuttgart · New York

70
M. Bröring, S. Link
PAPER
(2) (a) For an overview, see: Sessler, J. L.; Weghorn, S. J.
MS (EI, 70 eV): m/z = 640 (M+).
Expanded, Contracted & Isomeric Porphyrins; Elsevier:
Oxford, 1997. (b) Setsune, J.-i.; Maeda, S. J. Am. Chem.
Soc. 2000, 122, 12405. (c) Wytko, J. A.; Michels, M.;
Zander, L.; Lex, J.; Schmickler, H.; Vogel, E. J. Org. Chem.
2000, 65, 8709.
Anal. Calcd for C22H32I2N2O4: C, 41.27; H, 4.72; N, 4.38. Found: C,
41.65; H, 4.72; N, 4.31.
3,3’-(1,4-Butandiyl)-5,5’-diethoxycarbonyl-4,4’-diethyl-2,2’-
bipyrrole (14)
(3) (a) Drews, A.; Schönemeier, T.; Seggeweis, S.; Breitmaier,
E. Synthesis 1998, 749. (b) Vogel, E.; Bröring, M.;
Weghorn, S. J.; Scholz, P.; Deponte, R.; Lex, J.; Schmickler,
H.; Schaffner, K.; Braslavsky, S. E.; Müller, M.; Pörting, S.;
Fowler, C. J.; Sessler, J. L. Angew. Chem., Int. Ed. Engl.
1997, 36, 1651; Angew. Chem. 1997, 109, 1725.
(c) Morosini, P.; Scherer, M.; Meyer, S.; Lynch, V.; Sessler,
J. L. J. Org. Chem. 1997, 62, 8848. (d) Vogel, E.; Binsack,
B.; Hellwig, Y.; Erben, C.; Heger, A. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2612; Angew. Chem. 1997, 109, 2725.
(e) Sessler, J. L.; Weghorn, S. J.; Lynch, V.; Fransson, K. J.
Chem. Soc., Chem. Commun. 1994, 1289. (f) Sepulveda-
Boza, S.; Breitmaier, E. Liebigs Ann. Chem. 1983, 894.
(g) Kazlauskas, K.; Marwood, F. F.; Murphy, P. T.; Wells,
R. J. Aust. J. Chem. 1982, 35, 215. (h) Dolphin, D.; Grigg,
R.; Johnson, A. W.; Leng, J. J. Chem. Soc. 1965, 1460.
(i) Grigg, R.; Johnson, A. W. J. Chem. Soc. 1964, 3315.
(j) Bullock, E.; Grigg, R.; Johnson, A. W.; Wasley, J. W. F.
J. Chem. Soc. 1963, 2326. (k) Johnson, A. W.; Kay, I. T.;
Rodrigo, R. J. Chem. Soc. 1963, 2336.
Compound 13 (18.5 g, 28.9 mmol) and di-tert-butyl dicarbonate
(13.8 g, 63.1 mmol) were suspended in anhyd CH2Cl2 (190 mL) and
treated with 4-dimethylaminopyridine (185 mg) at r.t. for 2 h. Silica
gel (20 g) was added to destroy excess anhydride, and after stirring
for 1 h, the mixture was filtered, the cake carefully washed with
CH2Cl2, and the combined organic washings were evaporated to
leave a yellowish semi-solid. This solid was dissolved in anhyd tol-
uene (270 mL), copper powder (22.4 g, 353 mmol) was added and
the slurry was refluxed for 3 d. Copper was filtered off over Celite
and the solids washed carefully with additional toluene. The com-
bined toluene solutions were washed with H2O (2 200 mL), dried
(Na2SO4), and evaporated to a brown, heavy oil. This was pyrolyzed
at 200 °C/20 mbar for 1 h, cooled to r.t., and treated with hexane in
a sonic bath for 15 min, whereupon the title compound solidified.
The fine, greenish powder was filtered with suction, washed with
hexane, and dried in vacuo to yield 9.71 g (87%) of 14; mp 177 °C.
1H NMR (400 MHz, CDCl3): = 1.11 (t, J = 7.4 Hz, 6 H,
CH3CH2pyr), 1.32 (t, J = 7.4 Hz, 6 H, CH3CH2O), 1.72 (br s, 4 H,
CH2CH2pyr), 2.59 (br s, 4 H, CH2CH2pyr), 2.72 (q, J = 7.4 Hz, 4 H,
CH3CH2pyr), 4.28 (q, J = 7.4 Hz, 4 H, CH3CH2O), 9.11 (br s, 2 H,
NH).
13C NMR (100.6 MHz, CDCl3): = 14.4 (CH3CH2O), 15.4
(CH3CH2pyr), 18.2 (CH3CH2pyr), 22.5 (CH2CH2pyr), 26.6
(CH2CH2pyr), 60.1 (CH3CH2O), 118.7 (C-5), 123.2 (C-3), 125.5
(C-2), 133.9 (C-4), 161.7 (CO2Et).
(4) Sessler, J. L.; Hoehner, M. C. Synlett 1994, 211.
(5) (a) Scrosati, B. Applications of Electroactive Polymers;
Chapman & Hall: London, 1993. (b) Rodriguez, J.; Grande,
H. J.; Otero, T. F. In Handbook of Organic Conductive
Molecules and Polymers; Nalwa, H. S., Ed.; Wiley: New
York, 1997, 415.
(6) Che, C.-M.; Wan, C.-W.; Lin, W.-Z.; Zhou, Z.-Y.; Lai, W.-
Y.; Lee, S.-T. Chem. Commun. 2001, 721.
MS (EI, 70 eV): m/z = 386 (M+).
Anal. Calcd for C22H32N2O4: C, 68.37; H, 7.82; N, 7.25. Found: C,
68.36; H, 7.74; N, 7.13.
(7) (a) Johnson, A. W.; Price, R. J. Chem. Soc. 1960, 1649.
(b) Bröring, M. Synthesis 2000, 1291. (c) Bröring, M.;
Griebel, D.; Hell, C.; Pfister, A. J. Porphyrins
Phthalocyanines 2001, 5, 708.
Acknowledgement
(8) (a) Dolphin, D.; Harris, R. L. N.; Huppatz, J. L.; Johnson, A.
W.; Kay, I. T.; Leng, J. J. Chem. Soc. (C) 1966, 98.
(b) Bröring, M.; Brandt, C. D.; Lex, J.; Humpf, H.-U.; Bley-
Escrich, J.; Gisselbrecht, J.-P. Eur. J. Inorg. Chem. 2001,
2549.
This work was funded by the Deutsche Forschungsgemeinschaft
(Emmy-Noether-Programm) and the Fonds der Chemischen Indu-
strie. The authors thank Professor H. Werner for his continuing sup-
port. Help with the NMR spectroscopic characterization by R.
Bertermann is gratefully acknowledged.
(9) Zhang, Y.; Thompson, A.; Rettig, S. J.; Dolphin, D. J. Am.
Chem. Soc. 1998, 120, 13537.
(10) (a) Vogel, E. Pure Appl. Chem. 1993, 65, 143. (b) Berlin,
A.; Bradamante, S.; Ferraccioli, R.; Pagani, G. A.;
Sannicolò, F. J. Chem. Soc., Chem. Commun. 1987, 1176.
(11) Paine, J. B. III.; Dolphin, D. Can. J. Chem 1978, 56, 1710.
(12) Tang, J.; Verkade, J. G. J. Org. Chem. 1994, 59, 7793.
References
(1) For a recent overview, see: Fürstner, A.; Fürstner, A.;
Grabowski, J.; Lehmann, C. W.; Kataoka, T.; Nagai, K.
ChemBioChem. 2001, 2, 60 and Ref. 4,9a,10cited therein.
Synthesis 2002, No. 1, 67–70 ISSN 0039-7881 © Thieme Stuttgart · New York