A new bipyrrole coupling reaction

Article abstract of DOI:10.1002/jhet.5570440338

(Chemical Equation Presented). Pyrrole 8 was converted to 10 in 4 steps, and 10 was coupled directly to bipyrroles 1 in a Sonogashira reaction, respectively at the 3,3′ positions.

Full text of DOI:10.1002/jhet.5570440338

May-Jun 2007
739
A New Bipyrrole Coupling Reaction
Edward B. Nikitin, Michael J. Nelson and David A. Lightner*
Department of Chemistry, University of Nevada
Reno, NV 89557-0020
Received July 24, 2006
R
H
CO2C2H5
3
R
N
Pd[P(C6H5)3]2Cl2
4
2
2'
5'
10
CuI, (C2H5)3N
HC C X
5
N
3'
4'
C2H5O2C
C2H5O2C
R'
H
N
R
H
1a: R =
1b: R =
1c: R =
1d: R =
C
C
C
C
C
C
C
C
Si(CH3)3
CH2OH
CH2CH2OH
C6H5
8: R = CO2CH2C6H5, R' = CH3
10: R = R' = I
Pyrrole 8 was converted to 10 in 4 steps, and 10 was coupled directly to bipyrroles 1 in a Sonogashira
reaction, respectively at the 3,3ꢀ positions.
J. Heterocyclic Chem., 44, 739 (2007).
R
3
H
N
INTRODUCTION
R
2 3 2'
CO2C2H5
CO C H
5'
H
2
2 5
N
4
5'
Bipyrroles first appeared in Chemical Abstracts in
1914, with ~550 citations to the present. In contrast, there
have been ~70,000 citations for biphenyl since 1904.
Among the five possible isomers of bipyrrole, 2,2ꢀ-
bipyrroles appear in the literature more frequently than
any other, although they generally appear late and
infrequently in the first half of the twentieth century.
Successful directed syntheses of bipyrroles began to
appear in the 1950s, most often by an Ullmann-type
radical recombination coupling of 2-iodopyrroles [1-4] –
although other coupling methods, e.g., FeCl3 with ꢁ-H
pyrroles, have been used [1,5]. In the following, we show
a new method for coupling 2-iodopyrroles that also inserts
acetylene groups at 3,3ꢀ of the resultant bipyrrole.
2
2'
4
N
5
5 2
3' 3' 4'
4'
C2H5O2C
C H O C
N
5
H
2
H
R
R
1a: R =
1a: R =
C
C Si(CH )
C Si(CH3)33 3
C
C
C
C
1b: R1b
=
: R =
C
C
CH OH
C CH OH
2
2
1c: R =
C CH CH OH
C C CH CH OH
1c : R =
1d: R =
2
2
2
2
C
C6H5
C C H
1d: R =
C
6
5
Figure 1. The target 3,3'-diacetylene-substituted
Figure 1. The target 3,3'-diacetylene-substituted
2,2'-bipyrroles of this work.ork.
2,2'-bipyrroles of this w
recognizable products were obtained. Realizing that the
Sonogashira reaction conditions (absent the acetylene
component) did not induce bipyrrole formation from
either 5 or 10, we attempted to convert 10 to its 5-iodo-4-
acetylene derivative using trimethylsilylacetylene in a
Sonogashira reaction. Surprisingly, the product obtained
in high yield was bipyrrole 1a and not the expected
5-iodo-3-trimethylsilylacetylene monopyrrole. This
substitution-coupling reaction using other mono-
substituted acetylenes (Scheme 1) led to good yields of
1c-1d. Thus unexpectedly, we found a higher yield
synthesis of 1a, 1b, 1c and 1d, with overall yields from 8
of 34%, 25% 30% and 19%, respectively.
The mechanism of formation of 1 from 10 is unclear.
However, since the Sonogashira conditions absent the
acetylene do not lead to bipyrrole formation, it seems
reasonable to assume the first step involves replacing the
4-iodo of 10 by the acetylene component, and the 5-iodo-
3-acetylene monopyrrole undergoes coupling to the
bipyrrole. Because ethyl 5-iodo-3-ethyl-4-methyl-
bipyrrole-2-carboxylate does not undergo coupling to a
RESULTS AND DISCUSSION
The target bipyrroles were 1a-1d (Figure 1), for which
we had devised a stepwise procedure (Scheme 1) from
pyrrole diester 8 that was synthesized by a Fischer-Knorr
condensation between ethyl butyrylacetate and benzyl
acetoacetate [6]. Two key steps were involved: Cu-
catalyzed bipyrrole formation (to 4) and a Sonogashira
reaction [7-9] to replace the 3,3ꢀ-diodo groups of 2 with
acetylene units that led to bipyrroles 1a, 1b and 1d in
overall yields of approximately 9%, 11% and 7%. The
low overall yields were viewed as unattractive and led us
to attempt to shorten the number of steps by going more
directly from 6 to 2 via the 4,5-diiodopyrrole 10 (Scheme
1). Thus, 6 was converted with conc. H2SO4 smoothly to
9, which provided 10 in 63% overall yield from 6 upon
treatment of 9 with iodine and potassium iodide in
aqueous bicarbonate. Attempted copper-catalyzed
coupling reaction of 10 failed to give 2, however, and no

740
E. B. Nikitin, M. J. Nelson and D. A. Lightner
Vol 44
Scheme 1 [a]
CO2CH2C6H5
ii
CO2C6H5
i
O
+
C2H5O2 C
C2H5O2C
N
H
C2H5O2C
O
8 (65%)
CO2CH2C6H5
CO2C6H5
R
R
C2H5O2C
C2H5O2C
iv
N
H
N
H
7: R = CHO
6: R = CO2H
5 (8 4%)
iii
iv
(78% from 8)
v
vi
R
R
H
N
CO2C2H5
C2H5O2C
R
N
H
N
H
C2H5O2C
R
9: R = COH
10: R = I
4: R = CO2CH2C6H5
3: R = CO2H
iv
vi
iv
2: R = I
(50% from 4)
[a] Reagents and conditions: i, HONO on ethyl butyrylacetate, then Zn/CH3CO2H/ꢃ while benzyl acetoacetate is added; ii, Br2/SO2Cl2/
CH3CO2H; iii, KMnO4/acetone; iv, I2, KI, NaHCO3; v, Cu/DMF; vi, conc. H2SO4; vii, Pd[P(C6H5)3]2Cl2/CuI/(C2H5)3N + HCꢄC-Si(CH3)3,
H-CꢄC-CH2OH, HCꢄC-CH2CH2OH or HCꢄCC6H5
and C-13 signal at 77.23 ppm unless otherwise noted. All GC-
MS spectra were obtained from a Varian CP-3800 mass
spectrometer. Melting points were taken on a Mel-Temp
capillary apparatus and are uncorrected. Combustion analyses
was performed by Desert Analytics, Tuscon, AZ. Infrared
spectra were recorded on a Perkin-Elmer FT-IR infrared
spectrophotometer model SPECTRUM 2000. All ultraviolet-
bipyrrole under Sonogashira reaction conditions, it
appears likely that the 4-acetylene group is necessary to
facilitate the coupling, perhaps by complexing with the
palladium reagent, thereby bringing it close to the 5-iodo
reaction center for bipyrrole formation.
Interestingly, the reaction conditions that successfully
provided a substituted bipyrrole from an ꢀ,ꢁ-diiodo-
pyrrole failed to convert 1,2-diiodobenzene to a biphenyl
and led only to disubstitution on the ring, as has been
shown previously [7-9]. Thus, reaction of 1,2-diiodo-
benzene with trimethylsilylacetylene yielded only 1,2-
bis(trimethyl(silylacetylenyl) benzene, and the product
from phenylacetylene was 1,2-di(phenyl-acetylenyl)
benzene. Apparently on the aromatic ring, the rate of
biphenyl coupling of the supposed mono-acetylene adduct
with an ortho iodine is slow compared to substitution with
the second acetylene group.
visible spectra were recorded on
a Perkin-Elmer ꢂ-12
spectrophotometer. Analytical thin layer chromatrography (tlc)
was carried out on J.T. Baker silica gel IB-F plates (125 μm
layer). For purification, radial chromatography was carried out
on Merck silica gel PF254 with calcium sulfate binder,
preparative layer grade. Flash column chromatography was
carried out using silica gel, 60-200 mesh (M. Woelm,
Eschwege). All solvents were reagent grade obtained from
Fisher or Acros, as was the ethyl butyrylacetate. Deuterated
chloroform, dichloro-methane and dimethylsulfoxide were from
Cambridge Isotope Laboratories.
Trimethylsilylacetylene,
propargyl alcohol, 3-butyn-1-ol and phenylacetylene were from
GFS Chemicals. Copper(I) iodide (Cu2I2, 98%, stock #26110, lot
#060674 was from Alfa Products. Copper powder (99% for
organic synthesis, batch #16920AB), Palladium(II) acetate and
bis(triphenyl-phosphine) palladium(II) chloride were from
Sigma Aldrich.
EXPERIMENTAL
All nuclear magnetic resonance (nmr) spectra were obtained
on a General Electric QE-300 or GN-300 at 300 MHz (proton)
and 75 MHz (C-13), respectively, in deuteriochloroform unless
otherwise indicated. Chemical shifts were reported in ppm
referenced to the residual chloroform proton signal at 7.26 ppm
Ethyl 4-carbobenzyloxy-5-methyl-3-n-propyl-1H-pyrrole-
2-carboxylate (8). A two liter three-necked round bottom flask
was equipped with a paddle stirrer, a dropping funnel and a
thermometer. Ethyl butyrylacetate (50.0 g, 0.316 moles) was

May-Jun 2007
A New Bipyrrole Coupling Reaction
741
added to 240 ml of glacial acetic acid and cooled in an ice bath
to 5°C. A solution of sodium nitrite (24.4 g, 0.32 moles) in
water (60 ml) was added dropwise over 1 hour. The solution
was then allowed to warm to room temperature and was stirred
for 4 hours. Benzyl acetoacetate (60.5 g, 0.315 moles) was
added all at once to the solution, followed by portions of zinc
dust (42 g, 0.64 g-atom total) with stirring. As the zinc was
added, the temperature of the flask slowly rose to 70°C. After
the addition was complete, the solution was kept between 65°C
and 75°C for 1.5 hours using a hot water bath. The solution was
then poured into 2 liters of ice water and stirred magnetically for
30 minutes. The precipitate was collected by vacuum filtration,
washed with water, and dissolved in dichloromethane. After
removal of the solvent under reduced pressure, the resulting
solid was recrystallized from ethanol to give 62.2 g, 0.319 mol
(65% yield) of the product as a colorless solid. It had mp 80-
81°C; GC-MS (m/z): 329 [M+•], 267, 238, 194, 192, 166; ir
(KBr): 3295, 2960, 2343, 1700, 1666, 1436, 1278, 1264, 1194,
1085, 698 cm-1; H nmr: 0.86 (t, 3H, J = 7.0 Hz), 1.36 (t, 3H, J =
7.0 Hz), 1.52 (m, 2H), 2.50 (s, 3H), 3.00 (t, 2H, J = 8.0 Hz), 4.32
(q, 2H, J = 7.0 Hz), 5.28 (s, 2H), 7.37 (m, 5H), 8.98 (brs, 1H)
ppm; C-13 nmr: 14.0, 14.3, 14.4, 24.5, 27.6, 60.3, 65.6, 112.6,
117.8, 128.0, 128.3, 128.5, 135.9, 136.5, 139.5, 161.8, 165.0
ppm. Anal. Calcd for C19H23NO4 (329.4): C, 69.30; H, 6.99; N,
4.26. Found: C, 69.15; H, 7.16; N, 4.41.
7.0 Hz), 1.39 (t, 3H, J = 7.0 Hz), 1.40 (m, 2H), 2.97 (t, 2H, J =
6.8 Hz), 4.37 (q, 2H, J = 7.0 Hz), 5.43 (s, 2H), 7.44 (m, 5H),
10.30 (brs, 1H) ppm; C-13 nmr (dimethylsulfoxide-d6): 13.6,
14.0, 23.8, 26.4, 60.1, 66.1, 118.3, 120.9, 127.2, 128.0, 128.1,
128.3, 131.7, 135.8, 159.9, 160.9, 164.3 ppm. Anal. Calcd for
C19H21NO6 (359.4): C, 63.51; H, 5.85; N, 3.90. Found: C,
63.60; H, 5.85; N, 3.86.
Ethyl 4-benzyloxycarbonyl-5-iodo-3-propyl-1H-pyrrole-2-
carboxylate (5). In a 600 ml beaker, 10.2 g (28.4 mmoles) of 3-
benzyloxycarbonyl-5-ethoxycarbonyl-4-propyl-1H-pyrrole -2-
carboxylic acid (6) was dissolved in 100 ml of hot ethanol.
Sodium bicarbonate (8.66 g) and 100 ml of water were added
carefully to the mixture. The mixture was then heated to 70°C
on a hot plate. Potassium iodide (13.8 g) and iodine (8.01 g)
were dissolved in 85 ml of water. The iodine mixture was then
added drop wise at such a rate as to minimize the gas evolution.
The endpoint was slightly purple colored. The contents of the
flask were cooled to 50°C and the precipitate was collected by
vacuum filtration. The precipitate was dissolved in chloroform
and dried over sodium sulfate. The sodium sulfate was removed
by gravity filtration, and the solvent was evaporated under
reduced pressure. The product was recrystallized from ethanol
to give 9.76 g (78%) as colorless needles with mp 154-155°C; H
nmr: 0.83 (3H, t, J = 7 Hz), 1.37 (3H, t, J = 7 Hz), 1.49 (2H,
sex., J = 8 Hz), 3.00 (2H, t, J = 8 Hz), 4.33 (2H, q, J = 7 Hz),
5.31 (2H, s), 7.41 (5H, m), and 9.26 (1H, br.s) ppm. C-13 nmr:
13.9, 14.3, 24.4, 27.7, 60.8, 66.2, 124.9, 128.2, 128.5, 128.6,
138.8 (135.76), 135.8 (135.5), 160.3, and 163.2 ppm. Anal.
Calcd for C18H20NIO4 (441.3): C, 49.00; H, 4.57; N, 3.17.
Found: C, 49.48; H, 4.71; N, 3.21.
Diethyl 3,3ꢀ-bis(benzyloxycarbonyl)-4,4ꢀ-dipropyl-2,2ꢀ-
bipyrrole-3,3ꢀ,5,5ꢀ-tetracarboxylate (4). In a 100-ml round
bottom flask, 9.66 g 21.9 mmoles) of 4-benzyl 2-ethyl 5-iodo-3-
propyl-pyrrole-2,4-dicarboxylate (5) was dissolved in 60 ml of
dry dimethylformamide. Activated copper (9.0 g) [10] was
added to the flask, which was then stoppered, covered with
aluminum foil, and stirred for 15 h. Chloroform (100 ml) was
then added to the mixture, and the unreacted copper was
removed by vacuum filtration and rinsed with 100 ml of
chloroform. The combined organic solutions were washed with
1 N aqueous hydrochloric acid (2 x 60 ml), brine (60 ml), and
saturated aqueous sodium bicarbonate (60 ml). The solution
was then dried over sodium sulfate, removed from the mixture
by gravity filtration and evaporated under reduced pressure to
yield a solid that was recrystallized from ethanol to give 3.78 g
(55%) of 4 as colorless needles. It had mp 165-166°C; H nmr:
0.72 (6H, t, J = 7 Hz), 1.42 (6H, t, J = 7 Hz), 1.43 (4H, sex., J =
8 Hz), 3.00 (4H, t, J = 8 Hz), 5.37 (4H, q, J = 7 Hz), 7.40 (10H,
m), and 14.2 (2H, br. s) ppm. C-13 nmr: 13.9, 14.3, 24.7, 28.0,
60.4, 67.5, 112.8, 119.8, 128.5, 128.6, 129.1, 129.9, 135.3,
136.6, 160.8 and 168.0 ppm. Anal. Calcd. C36H40N2O8 (628.7):
C, 68.79; H, 6.37; N, 4.46. Found: C, 68.83; H, 6.66; N, 4.54.
Diethyl 3,3ꢀ-diiodo-4,4ꢀ-dipropyl-2,2ꢀ-bipyrrole-5,5ꢀ-di-
carboxylate (2). Tetraester 4 (0.97 g) was carefully added in
portions to 10 ml of concentrated sulfuric acid at 50°C and stirred
for 5 minutes. The solution was then poured into 200 ml of ice
water and was stirred vigorously for 10 minutes. The precipitate
(0.70 g), collected by vacuum filtration, was used without further
purification. In a 50-ml beaker, 0.70 g of crude 5,5ꢀ-diethoxy-
carbonyl-4,4ꢀ-dipropyl-2,2ꢀ-bipyrrole-3,3ꢀ-dicarboxylic acid (3)
was dissolved in 10 ml hot ethanol. Sodium bicarbonate (0.7 g)
and 10 ml of water were carefully added to the mixture. The
3-Benzyloxycarbonyl-5-ethoxycarbonyl-4-propyl-1H-pyrrole-
2-carboxylic acid (6). Mixed diester 8 (24.6 g, 74.8 mmoles)
was added to 100 ml of glacial acetic acid in a three-neck round
bottom flask. The contents were stirred mechanically and
cooled to 10°C in an ice bath. Bromine (3.7 ml, 74 mmoles)
was added to the solution all at once. Freshly distilled sulfuryl
chloride (18.9 ml, 226 mmoles) was then added dropwise over
1.5 hours. During the addition, care was used to ensure that the
mixture was stirred vigorously (the contents of the flask will
precipitate massively during addition). After all of the sulfuryl
chloride has been added, the solution was allowed to reach room
temperature and was stirred for 4.5 hours. Water (40 ml) was
then added dropwise. After the addition was complete, the
solution was heated on a hot water bath at 60°C for 30 minutes.
The solution was then poured into one liter of ice water and
stirred. The precipitate was collected by vacuum filtration and
washed with water. The precipitate was dissolved in saturated
aqueous sodium bicarbonate. The undissolved aldehyde (7) was
collected by vacuum filtration and the filtrate was acidified with
dilute hydrochloric acid. The resulting precipitate was collected
by vacuum filtration, washed with water, and dried. Acid (6)
was recrystallized from 2-propanol to afford 11.25 g, 43.4
mmol. Aldehyde (7) (the side product from this reaction) was
dissolved in 150 ml of reagent acetone and a solution of
potassium permanganate (5 g in 200 ml of acetone/water (1:1))
was added over 1 hours. After 10 hours of stirring at room
temperature, the purple solution was poured into 250 ml of 10%
aqueous NaHSO3, and the mixture was extracted with
chloroform (3 x 200 ml). The combined chloroform extracts
were washed with water (2 x 200 ml) and with saturated aqueous
sodium chloride (1 x 200 ml, dried over sodium sulfate, filtered,
and evaporated, leaving crude resulting acid which was also
recrystallized from 2-propanol. The combined yield of 3-
benzyloxy-carbonyl-5-ethoxy-carbonyl-4-propyl-1H-pyrrole-2-
carboxylic acid (6) was 21.3 g, 59.4 mmol, (79%). It had mp
133-134°C; ir (KBr): 3261, 1737, 1695, 1492, 1443, 1269,
1011, 764 cm-1; H nmr (dimethylsulfoxide-d6): 0.76 (t, 3H, J =

742
E. B. Nikitin, M. J. Nelson and D. A. Lightner
Vol 44
mixture was then heated to 65°C on a hot plate. Potassium iodide
(2.20 g) and iodine (1.26 g) were dissolved in 15 ml of water and
used to treat the diacid as described for 5 above. The product (2)
was recrystallized from 2-propanol-water to give 0.44 g (47% from
4 as colorless needles with mp 151-152°C, H nmr: 1.00 (6H, t, J =
7 Hz), 1.39 (6H, t, J = 7 Hz), 1.57 (4H, m), 2.75 (4H, t, J = 8 Hz)
4.36 (4H, q, J = 7 Hz) and 10.06 (2H, br. s) ppm; C-13 nmr: 13.9,
14.3, 23.5, 30.1, 60.6, 69.3, 119.7, 126.0, 135.3 and 160.2 ppm.
Anal. Calcd for C20H26I2N2O6·H2O (630.3): C, 38.11; H, 4.16; N,
4.44. Found: C, 38.14; H, 4.22 N, 4.49.
Ethyl 4,5-diiodo-3-propyl-1H-pyrrole-2-carboxylate (10).
3-Benzyloxycarbonyl-5-ethoxycarbonyl-4-propyl-2-carbox-
ylic acid (6) (20 g, 55.65 mmoles) was carefully added in
portions to 150 ml of concentrated sulfuric acid at 50°C and was
stirred for 5 minutes. The solution was then poured into 1000
ml of ice water and was stirred vigorously for 10 minutes. The
precipitate was then collected by vacuum filtration. The crude
product was sensitive toward decarboxylation and was used in
the next step without further purification. It had mp 134-135°C
(dec.); ir (KBr): 3447, 3261, 2594, 1737, 1693, 1623, 1268,
1011, 811 cm-1; H nmr (dimethylsulfoxide-d6): 0.85 (t, 3H, J =
7.4 Hz), 1.27 (t, 3H, J = 7.2 Hz), 1.47 (m, 2H), 2.76 (t, 2H, J =
7.4 Hz), 4.24 (q, 2H, J = 7.2 Hz), 12.51 (s, 1H), 13.37 (s, 1H);
C-13 nmr (dimethylsulfoxide-d6): 13.8, 14.0, 23.8, 26.5, 60.2,
118.5, 121.4, 127.4, 133.4, 159.9, 101.0, 167.0.
In a 1000 ml beaker, 10 g (37.1 mmoles) of crude 5-
ethoxycarbonyl-4-propyl-1H-pyrrole-2,3-dicarboxylic acid (9)
was dissolved in 70 ml of hot ethanol. Sodium bicarbonate (31.2
g, 371 mmoles) in 200 ml of water was carefully, in portions
added to the mixture. The mixture was then heated to 65°C on a
hot plate. Potassium iodide (18.4 g, 111 mmoles) and iodine (22.6
g, 178 mmoles) were dissolved in 350 ml of water at 50-55°C.
The iodine mixture was then added dropwise only as quickly as it
was decolorized to minimize (CO2) gas evolution. The endpoint
was colored slightly purple. The contents of the flask were cooled
to 50°C, and the precipitate was collected by vacuum filtration.
Then it was dissolved in dichloromethane and dried over
anhydrous sodium sulfate. The sodium sulfate was removed by
vacuum filtration, and the solvent was evaporated under reduced
pressure. The product was recrystallized from 2-propanol/water
(50/50, by volume) to give 15.2 g, 35 mmoles of diiodide 10 (63%
from (6)) as a white solid. It had mp 154-155°C; ir (KBr): 3245,
2978, 1694, 1669, 1422, 1264, 1231, 1182, 781 cm-1; H nmr: 0.95
(t, 6H, J = 7.5 Hz), 1.38 (t, 6H, J = 7.0 Hz), 1.56 (m, 4H), 3.06 (t,
4H, J = 7.5 Hz), 4.34 (q, 4H, J = 7.0 Hz), 9.18 (brs, 2H) ppm; C-
13 nmr: 14.1, 14.6, 23.7, 31.5, 60.9, 82.1, 84.2, 124.5, 136.6,
160.6 ppm. Anal. Calcd. for C10H13I2NO2 (433.0): C, 27.74; H,
3.03; N, 3.23. Found: C, 27.50; H, 2.74; N, 3.39.
Diethyl 3,3ꢀ-Bis(trimethylsilylethynyl)-4,4ꢀ-di-propyl-2,2ꢀ-
bipyrrole-5,5ꢀ-dicarboxylate (1a). Diiodopyrrole 10 (0.3 g, 0.7
mmoles), bis(tri-phenylphosphine)palladium(II) dichloride (0.05
g, 0.07 mmoles), cuprous iodide (0.03 g, 0.14 mmoles) and
(trimethylsilyl)acetylene (0.21 g, 0.3 ml, 2.1 mmoles) were
dissolved in 15 ml of freshly distilled triethylamine. The mixture
was heated at 60°C and stirred under nitrogen overnight. After
cooling, the solvent was evaporated at reduced pressure, and the
crude product was redissolved in dichloromethane then vacuum
filtered through a pad of silica gel. The solvent was evaporated to
yield product 1a, which was purified by radial chromatography
(CH2Cl2 eluent). The yield of (1b) was 0.27 g, 0.49 mmol (70%).
It had mp 123-124°C; ir (KBr): 3248, 2958, 2164, 1676, 1456,
1263, 1105, 884 cm-1; H nmr: 0.33 (s, 18H), 0.95 (t, 6H, J = 7.5
Hz), 1.37 (t, 6H, J = 7.2 Hz), 1.63 (m, 4H), 2.83 (t, 4H, J = 7.5
Hz), 4.36 (q, 4H, J = 7.2 Hz), 10.28 (brs, 2H) ppm; C-13 nmr:
0.26, 14.1, 14.8, 23.8, 27.8, 60.5, 99.5, 101.5, 104.3, 119.1, 128.6,
136.1, 160.7 ppm. Anal. Calcd. for C30H44N2O4Si2 (552.9):
C, 65.18; H, 8.02; N, 5.07. Found: C, 65.15; H, 7.91; N, 4.72.
Diethyl 3,3ꢀ-bis(3-hydroxyprop-1-ynyl)-4,4ꢀ-di-n-propyl-
2,2ꢀ-bipyrrole-5,5ꢀ-dicarboxylate (1b). Diiodopyrrole 10 (0.3
g. 0.7 mmoles), bis(triphenyl-phosphine)palladium(II) dichloride
(0.05 g, 0.07 mmoles), cuprous iodide (0.03 g, 0.14 mmoles) and
propargyl alcohol (0.16 g, 0.16 ml, 2.8 mmoles) were treated as
above the syntheses of 1a. The yield of (1b) was 0.17 g, 0.36
mmol (51%). It had mp 130-131°C; ir (KBr): 3450, 1675, 1454,
1278, 1140, 780 cm-1; H nmr: 0.94 (t, 6H, J = 7.4 Hz), 1.35 (t,
6H, J = 7.1 Hz), 1.54 (m, 4H), 2.70 (t, 4H, J = 5.9 Hz), 3.01 (t,
4H, J = 7.4 Hz), 3.85 (t, 4H, J = 5.9 Hz), 4.32 (q, 4H, J = 7.1
Hz), 9.50 (brs, 2H), 13.5 (brs, 2H) ppm; C-13 nmr: 14.1, 14.5,
23.7, 30.4, 51.7, 60.9, 77.9, 93.5, 120.3, 120.6, 132.2, 135.12,
160.1 ppm. Anal. Calcd. for C26H32N2O6 (468.6): C, 66.65; H,
6.88; N, 5.98. Found: C, 66.43; H, 7.24; N, 6.11.
Diethyl 3,3ꢀ-Bis(4-hydroxybut-1-ynyl)-4,4ꢀ-di-propyl-2-2ꢀ-
bipyrrole-5,5ꢀdicarboxylate (1c). Diiodopyrrole 10 (0.3 g, 0.7
mmoles), bis(triphenyl-phosphine)palladium(II) dichloride (0.05
g, 0.07 mmoles), cuprous iodide (0.03 g, 0.14 mmoles) and 3-
butyn-1-ol (0.2 g, 0.21 ml, 2.8 mmoles) were treated as above
for 1a. The yield of (1c) was 0.21 g, 0.43 mmol (62%). It had
mp 139-140°C; ir (KBr): 3415, 3249, 2957, 2150, 1677, 1454,
1277, 1140, 793 cm-1; H nmr: 0.94 (t, 6H, J = 7.4 Hz), 1.35 (t,
6H, J = 7.1 Hz), 1.54 (m, 4H, 2.70 (t, 4H, J = 7.1 Hz), 9.50 (brs,
2H) ppm; C-13 nmr: 14.0, 14.2, 24.2, 24.5, 27.5, 60.2, 60.8,
73.8, 94.4, 118.6, 119.9, 121.3, 134.6, 160.9 ppm. Anal. Calcd.
for C28H36N2O6 (496.6): C, 67.72; H, 7.31; N, 5.64. Found: C,
67.74; H, 7.38; N, 5.69.
Diethyl 3,3ꢀ-Bis(phenyl-1-ethynyl)-4,4ꢀ-di-propyl-2-2ꢀ-bi-
pyrrole-5,5ꢀdicarboxylate (1d).Diiodopyrrole 10 (0.3 g, 0.7
mmoles), bis(tri-phenyl-phosphine)palladium(II) dichloride
(0.05 g, 0.07 mmoles), cuprous iodide (0.03 g, 014 mmoles) and
phenylacetylene (0.36 g, 0.38 ml, 3.5 mmoles) were dissolved in
15 ml freshly distilled triethylamine and treated as above for 1a.
The yield of (1d) was 0.15 g, 0.27 mmole (38%). It had mp
124-125°C; ir (KBr): 3246, 2249, 1705, 1675, 1456, 1263,
1105, 692 cm-1; H nmr (d2-dichloromethane): 0.95 (t, 6H, J = 7.4
Hz), 1.37 (t, 6H, J = 7.14 Hz), 1.57 (m, 4H), 3.05 (t, 4H, J = 7.4
Hz), 4.32 (q, 4H, J = 7.14 Hz), 7.39 (m, 6H), 7.54 (m, 4H), 9.44
(brs, 2H) ppm; C-13 nmr: 14.2, 14.6, 23.9, 27.8, 60.6, 83.5,
95.9, 104.3, 119.4, 123.3, 128.3, 128.6, 128.7, 131.7, 135.9,
160.7 ppm. Anal. Calcd. for C36H36N2O4 (560.7): C, 77.12; H,
6.47; N, 5.00. Found: C, 76.97; H, 6.47; N, 5.00.
Acknowledgments. We thank the National Institutes of
Health (NICHD 17779) for generous support. E.N. was an R.C.
Fuson Graduate Assistant.
REFERENCES AND NOTES
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