Fast, efficient syntheses of linear poly(dipyrromethene)s

Article abstract of DOI:10.1139/v02-179

The synthesis of three octapyrrolic, 8-10, and four dodecapyrrolic, 15-18, oligomers is reported. They are linear poly(dipyrromethene)s and potential ligands as building blocks for supramolecular architectures through self-assembly. Octapyrrolic oligomers 8-10 were prepared in 90-95% yields by condensation of 2 equiv of a tripyrrolic compound 4 with 1 equiv of diformyldipyrrolic compounds 5-7. A similar procedure, involving the condensation of 2 equiv of a pentapyrrolic starting material 13 with 1 equiv of 5-7 or 14, was found to give rise to the corresponding dodecameric systems 15-18 in 41-56% yields.

Full text of DOI:10.1139/v02-179

1668
Fast, efficient syntheses of linear
poly(dipyrromethene)s
Qingqi Chen and David Dolphin
Abstract: The synthesis of three octapyrrolic, 8–10, and four dodecapyrrolic, 15–18, oligomers is reported. They are
linear poly(dipyrromethene)s and potential ligands as building blocks for supramolecular architectures through self-
assembly. Octapyrrolic oligomers 8–10 were prepared in 90–95% yields by condensation of 2 equiv of a tripyrrolic
compound 4 with 1 equiv of diformyldipyrrolic compounds 5–7. A similar procedure, involving the condensation of
2 equiv of a pentapyrrolic starting material 13 with 1 equiv of 5–7 or 14, was found to give rise to the corresponding
dodecameric systems 15–18 in 41–56% yields.
Key words: poly(dipyrromethene), linear polypyrroles, dipyrromethane, dipyrromethene.
Résumé : On rapporte la synthèse de trois oligomères octapyrroliques (8–10) et de quatre dodécapyrroliques (15–18).
Il s’agit de poly(dipyrrométhènes) linéaires et des ligands potentiels comme blocs pouvant servir à la construction
d’architectures supramoléculaires par le biais d’autoassemblages. Les oligomères octapyrroliques 8–10 ont été préparés
avec des rendements allant de 90 à 95% par le biais de condensations de deux équivalents d’un composé tripyrrolique
(4) avec un équivalent de composés diformylpyrroliques (5–7). Une procédure semblable impliquant la condensation de
deux équivalents d’un produit de départ pentapyrrolique (13) avec un équivalent de composés 5–7 ou 14 conduit à la
formation des systèmes dodécamères correspondant (15–18) avec des rendements allant de 41 à 56%.
Mots clés : poly(dipyrrométhène), polypyrroles linéaires, dipyrrométhane, dipyrrométhène.
[Traduit par la Rédaction] Chen and Dolphin 1675
Introduction
bis(dipyrromethene) ligand – CoII complex exists in a helical
conformation. Since then several crystal structures of
2:2 biladiene-ac ligand – MII complexes have been reported
where the 2:2 complex existed as a helix (10). Our group re-
examined these reactions (6) and explored the use of a
2,2-spacer between dipyrromethene units (such as III) and
the 3,3>- positions (such as IV) and hexapyrins (V)
(Scheme 1).
Like biladienes-ac (II), bis(dipyrromethenes) (III) and
hexapyrrins (V) reacted with ZnII to form a double stranded
helical complex (5), while the complex of the 3,3>-
bidipyrromethene IV (n = 0) with ZnII showed triangular ge-
ometry with the ligand linking the three metal centers in an
overlapping progressive fashion. For each ligand one
dipyrromethene binding domain lies above the averaged
plane of the molecule, while the other dipyrromethene lies
below this plane (Scheme 2).
Dipyrromethenes (I) are yellow colored and fully conju-
gated flat compounds containing 10-ꢀ-electrons and can be
precursors of chlorins; expanded, contracted, and isomeric
porphyrins (1); bilirubins (2); biliverdin (2); and many other
bile pigments (3). They have been extensively used in the
synthesis of porphyrins (1) and linear polypyrroles (4). Ow-
ing to their stable monoanionic nature, dipyrromethenes have
been found to be useful ligands for a variety of metal ions
(5). In addition, bile pigments containing dipyrromethene
moieties linked by a methylene group such as biladienes-ac
(II) are useful ligands for the formation of well-defined ar-
chitectures through self-assembly (6). A salient feature of
dipyrromethene superstructures is that counterions are not
required, since the dipyrromethene unit is a monoanionic
ligand and the complex will be neutral when chelated with
divalent metal ions. This is in contrast to bipyridine ligands,
the standard building blocks for supramolecular assemblies
used by Lehn and co-workers (7, 8).
To extend our work, we were interested in linear
polydipyrromethenes, which include 2,2>-linked (A), 3,3>-
linked (B), 3,3>- sulfur bridged (C), and 2,2- directly linked
intermediates (D). In this paper we will report on the synthe-
sis and characterization of novel ligands that contain multi-
ple dipyrromethene units.
The use of dipyrromethenes as novel ligands to build dou-
ble helical supramolecules was originally proposed by one
of us in 1965 (9), when it was suggested that a 2:2
Received 15 April 2002. Published on the NRC Research Press Web site at http://canjchem.nrc.ca on 17 December 2002.
Q. Chen1 and D. Dolphin.2 Department of Chemistry, The University of British Columbia, 2036 Main Mall, Vancouver, BC V6T 1Z1,
Canada.
1Present address: Synapse Technologies Inc., 6660 NW Marine Drive, Vancouver, BC V6T 1Z4, Canada.
2Corresponding author (e-mail: ddolphin@qltinc.com).
Can. J. Chem. 80: 1668–1675 (2002)
DOI: 10.1139/V02-179
© 2002 NRC Canada

Chen and Dolphin
1669
Scheme 1.
Scheme 2.
methylpyrrole (1) via two steps, as shown in Scheme 3.
Briefly, the procedure involved first treatment of 1 with
pyrrole at reflux in a mixture of p-toluenesulfonic acid and
dichloromethane or at 40oC in acetic acid, followed by puri-
fication of the reaction mixture by direct crystallization from
dichloromethane–hexane. The asymmetric dipyrromethane 2
was obtained in 66% yield. Acid-catalyzed coupling of this
intermediate with 3,4,5-trimethyl-5-formylpyrrole (3) then
afforded the requisite hydrobromide salt of tripyrrole 4 in an
86% yield after crystallization.
Once 4 was in hand, the synthesis of the target com-
pounds 8–10 proved straightforward. After simple precipitat-
ing using anhydrous ether, the acid-catalyzed condensation
of 2 equiv of 4 and 1 equiv of 5–7 in methanol–dichloro-
methane was found to give the desired linear octapyrrins
8–10 as their corresponding tetrahydrobromide salts, in ex-
cellent yields. (detailed in Scheme 3).
Our synthetic procedure for dodecapyrrins 15–18 is out-
lined in Schemes 4 and 5. For this purpose, the key precursor
13 was required; this was prepared from 5-acetoxymethyl-
pyrrole 1a via two steps. The procedure involved first treat-
ing 1 with the 5-unsubstituted 2-formylpyrrole (11) at
50oC in acetic acid or at room temperature in a mixture of
dichloromethane and p-toluenesulfonic acid. Crystallization
from dichloromethane–hexane gave the asymmetric dipyrro-
Linear polypyrroles such as hexanornonapyrrin (11a),
decahydrohexapyrrin (11b–11d), and pentapyrrole (11e)
have been recently reported and characterized. However,
synthetic methods for linear oligopyrroles containing more
than three dipyrromethene units are not currently available.
The key precursor required for the synthesis of 8–9 was
tripyrrole 4. It was synthesized from the known 5-acetoxy-
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Can. J. Chem. Vol. 80, 2002
Scheme 3.
Scheme 4.
carbonylpyrrole (1a) (12), 3,4,5-trimethyl-2-formyl-pyrrole
(3) (13), bis(2,4-dimethyl-5-formyl-pyrrole-3-yl) sulfide (5)
(14), 5-methyl-2-benzoxycarbonylpyrrole (15), 5,5>-diformyl-
4,4>-dimethyl-3,3>-diethyl-dipyrromethane 7 (14), 3-methyl-
4-ethyl-2-formylpyrrole (11) (16), and 5,5>-diformylbi-
pyrrole (14) (15) were synthesized according to the previ-
ously reported procedures.
methane 12 in 72% yield. Condensation of 12 with tripyrrole
acid, generated in situ by treating 4 with trifluoroacetic acid
at room temperature for 20 min, afforded the desired inter-
mediate as the dihydrobromide salt 13 in 93% yield after pre-
cipitating with anhydrous ether. Acid-catalyzed condensation
between 14 and 2 equiv of 13 with 1 equiv of 5–7 gave, in
good yields, the desired dodecapyrrins 15–18 as their corre-
sponding hexahydrobromide salts.
5,5>-Bisethoxycarbony-2,2>-dimethyl-3,3>-
dipyrromethane
Paraformaldehyde (1.40 g, 47 mmol, 2.0 mol equiv) was
suspended in ethanol (300 mL) containing hydrochloric acid
(33%, 5 mL). The mixture was stirred with heating until all
Experimental section
5-Acetoxymethyl-4-ethyl-3-methyl-2-tert-butoxycarbonyl-
pyrrole (1) (12), 5-acetoxymethyl-3,4-dimethyl-2-tert-butoxy-
© 2002 NRC Canada

Chen and Dolphin
1671
Scheme 5.
the solid dissolved. After cooling to room temperature,
2-benzoxycarbonyl-5-methylpyrrole (20 g, 46.8 mmol) was
added. The mixture was allowed to stir at 40oC for 3 h. Af-
ter removal of solvent, the residue was crystallized from
methanol. The product was obtained as white crystals
(11.32 g, 55%); mp 222–224oC. 1H NMR (200 MHz,
CDCl3) (ppm) ꢁ: 2.20 (s, 6H, 2 CH3), 3.20 (s, 2H, CH2),
5.20 (s, 4H, 2OCH2), 6.60 (s, 2H, 2 pyrrolyl-H), 7.40 (m,
10H, 2 phenyl), 9.20 (s, 2H, 2NH). 13C NMR (50 MHz,
CDCl3) (ppm) ꢁ: 11.57 (CH3), 19.51 (s, CH2), 65.55
(OCH2), 113.13, 116.74, 119.38, 121.71, 128.12, 128.53,
130.76, 136.43, 162.55 (COO). LSIMS m/e: 443 ([M+ + 1]).
Anal. calcd. for C27H26N2O4: C 73.29, H 5.92, N 6.33;
found: C 73.02, H 5.90, N 5.98.
161.33 (COO). Anal. calcd. for C13H14N2O4: C 59.54, H 5.38,
N 10.68; found: C 59.33, H 5.28, N 10.39.
5-tert-Butoxycarbonyl-4-methyl-3-
methoxycarbonylmethyl-2,2>-dipyrromethane (2)
Method A
A 500 mL three-necked, round-bottomed flask equipped
with magnetic stirrer bar and a nitrogen inlet was charged
with 5-acetoxymethyl-4-ethyl-3-methyl-2-tert-butoxycarbonyl-
pyrrole (1, 10.0 g, 35.5 mmol) and acetic acid (250 mL). Af-
ter 20 min of stirring under nitrogen, pyrrole (2.86 g,
42.7 mmol, 1.2 mol equiv) and p-toluenesulfonic acid
monohydrate (330 mg) were added. The reaction mixture
was stirred at 40oC overnight. The solvent was removed un-
der vacuum. The residue was taken into dichloromethane
(500 mL) and washed successively by water (2 × 100 mL),
aqueous saturated sodium bicarbonate (2 × 100 mL), and
saturated brine (100 ml). After drying over anhydrous so-
dium sulfate and removing solvent under vacuum, the resi-
due was crystallized from dichloromethane–hexane to give
the product (3.33 g, 32%).
1,2-Bis(5-carboxy-2,4-dimethyl-pyrrole-3-yl)methane
1,2-Bis(5-benzoxycarbonyl-2-methylpyrrole-3-yl)methane
(20 g, 63 mmol) was dissolved in tetrahydrofuran (400 mL).
Palladium on carbon (10%, 1.0 g) and triethylamine (1 mL)
were added to this solution. The mixture was stirred for 20 h
under hydrogen at atmospheric pressure and room tempera-
ture. The catalyst was removed by filtration. After removal
of solvent, the residue was dried under vacuum. The product
was obtained as a white powder (16 g, 98%), which was
used directly for the next step without further purification.
An analytical sample was purified by twice repeating the
following procedure: the crude product (100 mg) was dis-
solved in aqueous saturated sodium bicarbonate (5 mL); the
mixture was then filtrated to remove any insoluble materials
and carefully adjusted to pH 4 with glacial acetic acid. The
white precipitate was collected by suction filtration; mp
220oC (decomposition temperature (dec.)). 1H NMR
(200 MHz, DMSO-d6) (ppm) ꢁ: 2.10 (s, 6H, 3 CH3), 3.30 (s,
2H, CH2), 6.40 (s, 2H, 2 pyrr-H), 11.02 (s, 2H, 2 COOH),
11.85 (s, 2H, 2 NH). 13C NMR (50 MHz, DMSO-d6) (ppm)
ꢁ: 9.30 (CH3), 19.20 (CH2), 119.90, 127.55, 131.44, 137.55,
Method B
A 500 mL three-necked, round-bottomed flask equipped
with a magnetic stirrer, nitrogen inlet, and reflux condenser
was charged with 5-acetoxymethyl-4-ethyl-3-methyl-2-tert-
butoxycarbonylpyrrole (1, 18.6 g, 66 mmol), pyrrole
(4.6 mL, 66 mmol, 1.0 mol equiv), and dichloromethane
(200 mL). The mixture was stirred at room temperature for
30 min while nitrogen was bubbled through the solution. p-
Toluenesulfonic acid monohydrate (250 mg) was then added
in one portion. The solution immediately turned yellow-red.
The mixture was stirred under reflux for 30 min. TLC then
showed the reaction was complete (CH2Cl2, 5-acetoxy-
methylpyrrole Rf = 0.4, product Rf = 0.5, and pyrrole Rf =
0.9). The product dipyrromethane turned yellow-red, pyrrole
© 2002 NRC Canada

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Can. J. Chem. Vol. 80, 2002
turned to brown-black, and the starting 5-acetoxymethyl-
pyrrole remained unchanged upon contacting the TLC plate
over bromine vapor. After cooling to room temperature,
triethylamine (1 mL) in methanol (5 mL) was added to neu-
tralize the acid. Solvent was completely removed under vac-
uum (first rotovapor, then high vacuum). The yellow semi-
solid was mixed with aqueous methanol (90%, 30 mL) and
ultrasonicated to aid solidification. The crude material was
immediately collected by suction filtration to yield the ex-
pected product (11.6 g, 61%), which was pure enough for
5,5>-Diformyl-2,2>-dimethyl-3,3>-dipyrromethane (6)
5,5>-Dicarboxy-2,2>-dimethyl-3,3>-dipyrromethane (3.0 g,
11 mmol) was suspended in trifluoroacetic acid (15 mL).
The mixture was stirred at 40oC until all the solid had
dissolved. The mixture was then cooled to –5oC using an
ice–salt bath. Trimethyl orthoformate (4.5 mL) was added
dropwise over 5 min and the mixture was allowed to stir
another 10 min before being poured into a solution of 10%
ammonia (100 mL), which was pre-cooled to 0oC. The
yellow-brown precipitated was collected by filtration and
washed with water. After drying under vacuum and crystal-
lizing from dichloromethane–hexane, the title compound
was obtained (2.1 g, 80%); mp 210–212oC. 1H NMR
(200 MHz, CDCl3) (ppm) ꢁ: 1.90 (s, 6H, 2 CH3), 3.30 (s,
2H, CH2), 6.35 (s, 2H, 2 pyrr-H), 9.40 (s, 2H, 2 CHO),
10.50 (s, 2H, 2NH). 13C NMR (50 MHz, CDCl3) (ppm) ꢁ:
9.50 (CH3), 19.50 (CH3), 121.44, 126.78, 130.45, 136.55,
177.55 (CHO). LSIMS m/e: 231 ([M+ + 1]). Anal. calcd.
for C13H14N2O2: C 67.81, H 6.13, N 12.17; found: C 67.51,
H 5.90, N 11.89.
1
subsequent use, as judged by H NMR. Note that this com-
pound is not very stable and should be stored in the dark and
1
at low temperature. mp 120–122oC. H NMR (200 MHz,
CDCl3) (ppm) ꢁ: 1.05 (t, J = 7.32 Hz, 3H, CH3), 1.50 (s, 9H,
3 CH3), 2.20 (s, 3H, CH3), 2.30 (q, J = 7.32 Hz, 2H, CH2),
3.80 (s, 2H, CH2), 5.80 (s, 1H, pyrrole-H), 6.05 (s, 1H,
pyrrole-H), 6.60 (s, 1H, pyrrole-H), 7.60 (s, 1H, NH), 8.60
(s, 1H, NH). 13C NMR (50 MHz, CDCl3) (ppm) ꢁ: 10.23
(CH3), 14.55 (CH3), 24.44 (CH2), 28.33 (CH2), 29.35 (CH3),
86.88 (OCMe3), 113.44, 114.55, 116.77, 123.55, 124.56,
o
125.44, 127.44, 128.33, 161.20 (COO). EI-MS (150 C) m/z
(%): 288 ([M+], 52), 232 (40), 165 (100), 147 (25). Anal.
calcd. for C17H24N2O2: C 70.80, H 8.39, N 9.71; found: C
70.60, H 8.61, N 8.53.
General procedure for 8–10
Tripyrrole (4, 100 mg, 0.20 mmol) was suspended in
trifluoroacetic acid (5 mL), and stirred at room temperature
until all solid had dissolved. To this brown-red mixture 5, 6,
or 7 (0.10 mmol, 0.5 mol equiv) was added under continu-
ous stirring. After 10 min, a mixture of dichloromethane
(20 mL), methanol (20 mL), and hydrogen bromide (48% in
acetic acid) was added. The red mixture was stirred at room
temperature and anhydrous ether (100 mL) was added. The
suspension was then allowed to stir for another 30 min. The
red solid was collected by suction filtration and washed with
anhydrous ether. The crude product was suspended in meth-
anol (50 mL) containing 5 drops of hydrogen bromide (45%
in glacial acid) and stirred at room temperature for 30 min.
The solid was collected by filtration to afford the expected
product. An analytic sample was obtained by repeating the
following procedure three times: The crude product
1-tert-Butoxycarbonyl-2-methyl-3-ethyl-12,13,14-tri-
methyl-4,5-dihydro-tripyrrin hydrogen bromide salt (4)
A 250 mL round-bottomed flask equipped with magnetic
stirrer bar was charged with 2-tert-butoxycarbonyl-3-methyl-
4-methoxycarbonylmethyl-dipyrromethane (2) (1.0 g,
3.47 mmol), 3,4,5-trimethyl-2-formyl-pyrrole (3) (0.48 g,
3.47 mmol, 1.0 mol equiv), dichloromethane (50 mL), and
methanol (20 mL). Hydrogen bromide (48% in glacial acetic
acid, 3 mL) was added with stirring. The red mixture was al-
lowed to stir for 2 h at room temperature. Anhydrous ether
(50 mL) was added and the suspension was allowed to stir
for another 30 min. The red solid was collected by suction
filtration and washed with anhydrous ether. The crude prod-
uct was suspended in methanol (50 mL) containing 5 drops
of hydrogen bromide (45% in glacial acid) and stirred for
30 min. The solid was collected by filtration (1.46 g, 86%).
An analytical sample was obtained as follows: crude product
was dissolved in a minimum amount of dichloromethane,
and methanol (~1 mL) containing a drop of hydrogen bro-
mide (45% in glacial acid) was added, followed by anhy-
drous ether to precipitate the product. The red solid was
collected by suction filtration; mp 220 (dec.). UV–Vis
(CH2Cl2) (nm): ꢂmax(ꢃ) = 483 (80 400). 1H NMR (200 MHz,
CDCl3) (ppm) ꢁ: 1.05 (t, J = 7.35 Hz, 3H, CH3), 1.55 (s, 9H,
3CH3), 2.00 (s, 3H, CH3), 2.20 (s, 6H, 2 CH3), 2.40 (q, J =
7.35 Hz, 2H, CH2), 2.60 (s, 3H, CH3), 4.25 (s, 2H, CH2),
6.30 (s, 1H, pyrrole-H), 7.00 (s, 1H, -CH=), 7.05 (s, 1H,
pyrrole-H), 10.05 (s, 1H, NH), 13.10 (s, 1H, NH), 13.20 (s,
1H, NH). 13C NMR (50 MHz, CDCl3) (ppm) ꢁ: 8.89 (CH3),
10.29 (CH3), 13.55 (CH3), 15.55 (CH3), 17.28 (CH3), 24.77
(CH2), 28.71 (CH3), 30.05 (CH2), 80.20 (OCMe3), 114.93,
119.57, 123.57, 124.13, 125.83, 126.11, 126.39, 127.33,
128.28, 133.13, 144.65, 152.49, 159.68 (C=N), 160.91
(COO). FAB-MS m/e: 408 ([M+ + 1]), 334. Anal. calcd. for
C25H33N3O2·HBr: C 61.47, H 7.02, N 8.60, Br 16.31; found:
C 61.58, H 7.10, N 8.32, Br 16.25.
(~20 mg) was dissolved in
a minimum amount of
trifluoroacetic acid. To this red mixture, dichloromethane
(1 mL) and methanol (1 mL) containing a drop of HBr (48%
in acetic acid) were added, followed by anhydrous ether to
precipitate the product. The red solid was collected by suc-
tion filtration.
Octapyrrin tetrahydrobromide salt (8)
Yield 95%, mp 300oC (dec.). UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 544 (110 600), 505 (97 700), 444 (81 000).
1H NMR (CDCl3/TFA-d, 9:1 (v/v), 200 MHz) (ppm) ꢁ: 1.05
(t, J = 7.35 Hz, 6H, 2CH3), 2.00 (s, 6H, 2CH3), 2.15 (s, 6H,
2CH3), 2.20 (s, 6H, 2CH3), 2.30 (s, 6H, 2CH3), 2.50 (q, J =
7.35 Hz, 4H, CH2), 2.60 (s, 6H, 2CH3), 2.70 (s, 6H, 2CH3),
4.50 (s, 4H, 2CH2), 6.40 (s, 2H, 2CH), 7.20 (s, 2H, 2CH),
7.26 (m, 4H, 4 pyrrole-H), 11.80–12.05 (m, 8H, 8NH).
1H NMR (CDCl3/TFA-d, 9:1 (v/v), 400 MHz) (ppm) ꢁ: 1.05
(t, J = 7.6 Hz, 6H, 2 CH3), 2.05 (s, 6H, 2CH3), 2.25 (s, 6H,
2CH3), 2.29 (s, 6H, 2CH3), 2.36 (s, 6H, 2CH3), 2.53 (q, J =
7.6 Hz, 4H, 2CH2), 2.64 (s, 6H, 2CH3), 2.66 (s, 6H, 2CH3),
4.52 (s, 4H, 2 CH2), 6.42 (s, 2H, 2 -CH=), 7.24 (m, 4H, 4
pyrrolyl-H), 12.10–12.40 (m, 8H, 8 NH). 13C NMR
(CDCl3/TFA-d, 9:1 (v/v), 100 MHz) (ppm) ꢁ: 8.78 (CH3),
© 2002 NRC Canada

Chen and Dolphin
1673
10.14 (CH3), 10.27 (CH3), 11.25 (CH3), 13.33 (CH3), 13.49
(CH3), 14.15 (CH3), 17.11 (CH2), 25.42 (CH2), 115.48,
119.22, 121.55, 124.14, 126.36, 126.51, 127.67, 127.84,
128.17, 129.74, 132.12, 145.06, 145.94, 147.44, 148.08,
151.48, 156.69 (C=N), 162.46 (C=N). FAB-MS m/z: 1017
([M+ + 1 + 2HBr]), 937 ([M+ + 2 + HBr]), 855 ([M+ + 1]).
HR-MS (LSIMS, matrix: thioglycerol) for C54H63N8S calcd.:
855.48964; found: 855.48906. Anal. calcd. for C54H62N8S·4HBr:
C 55.02, H 5.64, N 9.51; found: C 55.33, H 5.86, N 9.38.
865.56457. Anal. calcd. for C57H68N8·4HBr: C 57.59, H 6.10,
N 9.43; found: C 57.43, H 6.31, N 9.21.
5-tert-Butoxycarbonyl-3,4-dimethyl-5>-formyl-4>-ethyl-3>-
methyl-2,2>-dipyrromethane (12)
Method A
A 250 mL three-necked, round-bottomed flask equipped
with a magnetic stirrer bar and a nitrogen inlet was charged
with 5-acetoxymethyl-3,4-dimethyl-2-tert-butoxycarbonylpyrrole
(3.44 g, 12.5 mmol) and acetic acid (100 mL). Nitrogen was
bubbled through the solution with stirring, and after 20 min
2-formyl-3-ethyl-4-methylpyrrole (1.71 g, 12.5 mmol,
1.0 mol equiv) was added. The reaction mixture was stirred
at 50oC overnight. The solvent was removed under vacuum
(rotovapor). The residue was taken up in dichloromethane
(200 mL) and washed successively with water (2 × 100 mL),
aqueous saturated sodium bicarbonate (2 × 100 mL), and
saturated brine (100 ml). After drying over anhydrous so-
dium sulfate and removing solvent (rotovapor), the solid was
crystallized from dichloromethane–hexane, yielding 0.85 g
(20%).
Octapyrrin tetrahydrobromide salt (9)
Yield 93%; mp 320oC (dec.). 1H NMR (CDCl3/TFA-d, 9:1
(v/v), 200 MHz) (ppm) ꢁ: 1.05 (t, J = 7.35 Hz, 6H, 2CH3),
2.00 (s, 6H, 2CH3), 2.18 (s, 6H, 2CH3), 2.20 (s, 6H, 2CH3),
2.45 (q, J = 7.35 Hz, 4H, CH2), 2.55 (s, 6H, 2CH3), 2.60 (s,
6H, 2CH3), 3.70 (s, 4H, 2CH2), 4.00 (s, 4H, 2CH2), 6.45 (s,
2H, 2CH), 7.05 (s, 2H, 2CH), 7.10–7.20 (m, 4H, 4 pyrrole-
H), 7.80 (s, 2H, 2 pyrrole-H), 11.80–12.05 (m, 8H, 8NH).
1H NMR (CDCl3/TFA-d, 9:1 (v/v), 300 MHz) (ppm) ꢁ: 1.10
(t, J = 7.5 Hz, 6H, 2CH3CH2), 2.00 (s, 6H, 2 CH3), 2.25 (s,
6H, 2 CH3), 2.28 (s, 6H, 2 CH3), 2.50 (q, J = 7.5 Hz, 4H,
2CH3CH2), 2.60 (s, 6H, 2 CH3), 2.70 (s, 6H, 2 CH3), 3.60 (s,
2 H, -CH2-Bridge-), 4.40 (s, 4H, 2 CH2 -Bridge-), 6.50 (s,
2H, 2 pyrrolyl-H), 7.00–7.30 (m, 8H, 4 -CH=, 4 pyrrolyl-H),
11.80–12.30 (m, 8H, 8 NH). 13C NMR (CDCl3/TFA-d, 9:1
(v/v), 75 MHz) (ppm) ꢁ: 8.60 (CH3), 9.86 (CH3), 10.14
(CH3), 12.83 (CH3), 13.37 (CH3), 14.10 (CH3), 17.08 (CH2),
21.75 (CH2), 25.18(CH2), 115.48, 124.12, 124.86, 126.60,
127.63, 127.85, 128.01, 129.73, 131.77, 132.49, 134.90,
144.69, 145.71, 147.68, 149.36, 150.01, 154.90 (C=N),
162.98 (C=N). FAB-MS m/z: 809 ([M+ + 1]). HR-MS
(LSIMS: matrix: thioglycerol) for C53H61N8 calcd.:
809.50192, found: 809.50203. UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 538 (111 400), 504 (81 800), 444 (108 400). Anal.
calcd. for C53H60N8·4HBr·0.5H2O: C 54.97, H 5.62, N 9.68;
found: C 55.16, H 5.83, N 9.36.
Method B
A 250 mL three-necked, round-bottomed flask equipped
with a magnetic stirrer, nitrogen inlet, and a reflux con-
denser was charged with 5-acetoxymethyl-3,4-dimethyl-2-
tert-butoxycarbonylpyrrole (1.94 g, 7.30 mmol), 4-methyl-3-
ethyl-2-formylpyrrole (1.0 g, 7.30 mmol, 1.0 mol equiv),
and dichloromethane (150 mL). The mixture was stirred at
room temperature for 30 min while nitrogen was bubbled
through the solution. p-Toluenesulfonic acid monohydrate
(150 mg) was then added in one portion. The solution turned
yellow-red immediately. The mixture was stirred under re-
flux for 30 min. TLC showed the reaction was complete
(CH2Cl2, 5-acetoxymethylpyrrole Rf = 0.4, product Rf = 0.5,
and pyrrole Rf = 0.9). The product dipyrromethane turned
red, the pyrrole turned brown-black, and the starting 5-
actoxymethylpyrrole remained unchanged upon contacting
the TLC plate over bromine vapor. After cooling to room
temperature, triethylamine (1 mL) in methanol (5 mL) was
added to neutralize the acid. Solvent was completely re-
moved under vacuum (first rotovapor, then high vacuum).
The yellow semi-solid was mixed with aqueous methanol
(90%, 30 mL) and ultrasonicated to aid solidification. The
suspension was kept at 0oC for 4 h. The solid was collected
by suction filtration to yield the product (1.80 g, 72%), mp
Octapyrrin tetrahydrobromide salts (10)
Yield 91%; mp 310oC (dec.). UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 555 (71 200), 499 (107 900), 445 (88 300), 380
(27 300). 1H NMR (CDCl3/TFA-d, 9:1 (v/v), 200 MHz)
(ppm) ꢁ: 1.05 (t, J = 7.35 Hz, 6H, 2CH3), 2.05 (s, 6H,
2CH3), 2.20 (s, 6H, 2CH3), 2.30 (s, 6H, 2CH3), 2.35 (s, 6H,
2CH3), 2.45 (q, J = 7.35 Hz, 4H, CH2), 3.60 (s, 6H, 2CH3),
4.50 (s, 4H, 2CH2), 4.80 (s, 2H, CH2), 7.20 (m, 8H,
4 pyrrole-H, 4 -CH=), 11.80–12.00 (m, 8H, 8 NH). 1H NMR
(CDCl3/TFA-d, 9:1 (v/v), 300 MHz) (ppm) ꢁ: 0.95 (m, 12H,
4 CH3CH2), 2.05 (s, 6H, 2 CH3), 2.25 (s, 6H, 2 CH3), 2.33
(s, 6H, 2 CH3), 2.40 (s, 6H, 2 CH3), 2.45 (m, 8 H, 4 CH3CH2),
4.50 (s, 4H, 2 -CH2-bridge), 4.70 (s, 2H, -CH2-bridge), 7.22
(s, 2H, 2 pyrrolyl-H), 7.35 (s, 2H, 2 pyrrolyl-H), 7.45 (s, 4H,
4 –CH=), 11.80–12.00 (m, 8H, 8 NH). 13C NMR (CDCl3/TFA-d,
9:1 (v/v), 75 MHz) (ppm) ꢁ: 8.60 (CH3), 9.97 (CH3), 9.99
(CH3), 10.13 (CH3), 13.44 (CH3), 13.83 (CH3), 13.97 (CH3),
17.07 (CH2), 17.33 (CH2), 24.88 (-CH2-bridge), 25.78
(CH2-bridge), 119.96, 121.99, 124.45, 124.92, 127.74,
127.80, 128.05, 128.24, 129.87, 131.31, 144.78, 145.20, 145.33,
147.45, 148.46, 148. 88, 150.84 (C=N), 162.36 (C=N).
FAB-MS m/z: 865 ([M+ + 1]), 665, 439. HR-MS (LSIMS,
matrix: thioglycerol) for C57H69N8 calcd.: 865.56452; found:
1
189–191oC. H NMR (200 MHz, CDCl3) (ppm) ꢁ: 1.02 (t,
J = 7.32 Hz, 3H, CH3), 1.45 (s, 9H, 3 CH3), 1.70 (s, 3H,
CH3), 1.75 (s, 3H, CH3), 1.95 (s, 3H, CH3), 2.50 (q, J =
7.32 Hz, 2H, CH2), 3.80 (s, 2H, CH2), 9.25 (s, 1H, CHO),
9.85 (s, 1H, NH), 10.80 (s, 1H, NH). 13C NMR (50 MHz,
CDCl3) (ppm) ꢁ: 8.85 (CH3), 9.00 (CH3), 10.67 (CH3), 16.49
(CH3), 17.35 (CH2), 28.58 (OC(CH3)3), 80.18(OCMe3),
116.88, 117.35, 119.33, 126.22, 127.55, 127.99, 137.40,
140.53, 161.35 (COO), 176.49 (CHO). EI-MS m/e (%): 402
(2), 344 ([M]+, 80), 288 (90), 271 (20), 259 (20), 244 (30),
149 (100). Anal calcd. for C20H28N2O3: C 69.74, H 8.19,
N 8.13; found: C 69.26, H 8.27, N 7.94.
© 2002 NRC Canada

1674
Can. J. Chem. Vol. 80, 2002
Anal calcd. for C84H98N12S·6HBr: C 56.25, H 5.80, N 9.37;
found: C 56.87, H 6.07, N 9.00.
Pentapyrrole (13)
Starting tripyrrole (4) (300 mg, 0.61 mmol) was suspended
in trifluoroacetic acid (10 mL) and stirred at room tempera-
ture for 10 min until all the solid had dissolved. A solution
of 5-tert-butoxycarbonyl-3,4-dimethyl-5>-formyl-4-ethyl-3-
methyl-2,2>-dipyrromethane (12) (211 mg, 0.61 mmol,
1.0 mol equiv) in dichloromethane (20 mL) was added to the
brown-red solution under continuous stirring. After 10 min,
a mixture of methanol (20 mL) and hydrogen bromide
(2 mL, 48% in acetic acid) was added. The red mixture was
allowed to stir for 3 h at room temperature. Anhydrous ether
(100 mL) was then added and the suspension was stirred for
another 30 min. The red solid was collected by suction fil-
tration and washed with anhydrous ether to afford the prod-
uct (450 mg, 93%); mp 252oC (dec.). UV–Vis (CH2Cl2)
(nm): ꢂmax(ꢃ) = 525 (71 800), 447 (62 800). 1H NMR
(CDCl3, 200 MHz) (ppm) ꢁ: 0.95 (t, J = 7.35 Hz, 3H, CH3),
1.00 (t, J = 7.35 Hz, 3H, CH3), 1.50 (s, 9H, 3 CH3), 1.80 (s,
6H, 2 CH3), 2.20 (m, 9H, 3 CH3), 2.40 (s, 6H, 2 CH3), 2.60
(q, J = 7.32 Hz, 2H, -CH2-), 3.40 (q, J = 7.32 Hz, 2H, -CH2-),
4.20 (s, 2H, -CH2-), 4.80 (s, 2H, -CH2-), 6.80 (s, 2H, 2 –CH=),
6.90 (s, 2H, 2 pyrrole-H), 7.20 (m, 2H, 2 pyrrole-H), 10.40
(s, 1H, NH), 13.20 (s, 2H, 2 NH), 13.40 (s, 2H, 2 NH).
FAB-MS m/z: 634 ([M+ + 1]), 425, 199. HR-MS (LSIMS,
matrix: thioglycerol) for C40H52N5O2, calcd.: 634.41210;
found: 634.41180. Anal calcd. for C40H51N5O2·2HBr·H2O:
C 59.04, H 6.84, N 8.61, Br 19.64; found: C 58.89, H 6.64,
N 8.66, Br 19.30.
Dodecapyrrin hexahydrobromide salt (16)
Yield 45%, mp 280oC (dec.). 1H NMR (CDCl3/TFA-d, 9:1
(v/v), 200 MHz) (ppm) ꢁ: 0.95 (t, J = 7.6 Hz, 6H, 2CH3),
1.05 (t, J = 7.6 Hz, 6H, 2CH3), 1.60 (s, 6H, 2 CH3), 1.90 (s,
6H, 2 CH3), 2.20 (m, 26H, 6 CH3, 4 CH2), 2.60 (m, 18H, 6
CH3), 3.40 (s, 2H, -CH2-bridge), 4.9–5.10 (m, 4H, 2 -CH2-
bridge), 7.30 (m, 12H, 6 pyrrole-H, 6 -CH=), 13.20–13.40
(m, 12H, 12 NH). LSIMS (matrix: thioglycerol) m/z: 1262
([M+ + 2]), 1064. HR-MS (LSIMS, thioglycerol) for
C83H97N12 calcd.: 1261.78809; found: 1261.79638. UV–Vis
(CH2Cl2) (nm): ꢂmax(ꢃ) = 554 (258 000), 486 (242 000), 442
(173 700), 369 (57 000). Anal. calcd. for C87H106N12·6HBr·H2O:
C 56.46, H 5.90, N 9.52; found: C 56.32, H 6.09, N 9.11.
Dodecapyrrin hexahydrobromide salt (17)
Yield 56%, mp 288oC (dec.). UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 569 (70 800), 539 (72 500), 498 (63 700), 450
1
(53 800), 377 (32 000). H NMR (CDCl3/TFA-d, 9:1 (v/v),
200 MHz) (ppm) ꢁ: 0.85 (t, J = 7.35 Hz, 6H, 2CH3), 1.05 (t,
J = 7.35 Hz, 6H, 2CH3), 1.20 (t, J = 7.35 Hz, 6H, 2CH3),
2.00 (m, 18H, 6 CH3), 2.30 (m, 26H, 6 CH3, 4 CH2), 2.60
(m, 10H, 2 CH3, 2 CH2), 4.50–4.80 (m, 10H, 5 CH2), 7.30
(m, 10H, 4 pyrrole-H, 6 -CH=), 12.00–12.40 (m, 12H, 12
NH). FAB-MS (matrix: 3-NBA) m/z: 1558 ([M+ + 3HBr]),
1399 ([M+ + HBr]), 1318 ([M+ + 2]), 1119, 878, 651, 465.
HR-MS (LSIMS, thioglycerol) for C87H106N12 calcd.:
1318.86634; found: 1318.86809. Anal calcd. for
C87H106N12·6HBr: C 57.59, H 6.15, N 9.32, Br 26.60; found:
C 57.61, H 6.00, N 9.07, Br 26.30.
General procedure for 15–18
The pentapyrrole (13, 100 mg, 0.125 mmol) was sus-
pended in trifluoroacetic acid (5 mL) and stirred at room
temperature for 10 min until all the solid had dissolved. To
this brown-red solution was added a solution of 5, 6, 7, or 14
(0.0625 mmol, 0.5 mol equiv) in dichloromethane (20 mL)
under continuous stirring. After 10 min, a mixture of metha-
nol (20 mL) and hydrogen bromide (2 mL, 48% in acetic
acid) was added. The red mixture was stirred for 3 h at room
temperature. Anhydrous ether (100 mL) was added and the
suspension was allowed to stir for another 30 min. The red
solid was collected by suction filtration and washed by an-
hydrous ether containing a few drops of HBr (48% in acetic
acid) to afford the expected product. An analytic sample was
obtained by repeating the following procedure three times:
the crude product (~20 mg) was dissolved in dichloro-
methane (1 mL), and methanol (1 mL) containing a few
drops of HBr (48% in acetic acid) was added, followed by
the addition of anhydrous ether to precipitate the product.
The red solid was collected by suction filtration.
Dodecapyrrin hexahydrobromide salt (18)
Yield 47%, mp 320oC (dec.). UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 585 (88 900), 515 (137 000), 475 (113 000), 446
(114 300). 1H NMR (CDCl3/TFA-d, 9:1 (v/v), 200 MHz)
(ppm) ꢁ: 0.95 (t, J = 7.6 Hz, 6H, 2CH3), 1.20 (t, J = 7.6 Hz,
6H, 2 CH3), 2.00 (s, 6H, 2 CH3), 2.05 (s, 6H, 2 CH3), 2.10
(s, 6H, 2 CH3), 2.20 (s, 6H, 2 CH3), 2.30 (s, 6H, 2 CH3),
2.36 (s, 6H, 2 CH3), 2.40 (q, J = 7.6 Hz, 2H, CH2), 2.50 (s,
6H, 2 CH3), 2.60 (q, J = 7.6 Hz, 2H, CH2), 4.60 (s, 2H,
CH2), 4.70 (s, 2H, CH2), 7.20 (m, 14H, 8 pyrrole-H, 6 -CH=),
12.00–12.40 (m, 12H, 12 NH). LSIMS (matrix: thioglycerol)
m/z: 1219 ([M+ + 1]). HR-MS (LSIMS, thioglycerol) for
C80H90N12 calcd.: 1218.74114; found: 1218.74182. Anal
calcd. for C80H90N12·6HBr·2H2O: C 55.17, H 5.75, N 9.65;
found: C 55.19, H 5.86, N 9.16.
Dodecapyrrin hexahydrogen bromide salt (15)
Yield 41%, mp 300oC (dec.). UV–Vis (CH2Cl2) (nm):
ꢂmax(ꢃ) = 565 (211 100), 543 (209 100), 494 (142 700), 448
(142 700), 376 (47 900). H NMR (CDCl3/TFA-d, 9:1 (v/v),
Conclusion
1
200 MHz) (ppm) ꢁ: 0.90 (br s, 6H, 2CH3), 1.40 (br s, 6H,
2CH3), 1.80 (s, 12H, 4 CH3), 2.00 (s, 12H, 4 CH3), 2.40 (m,
26H, 6 CH3, 4 CH2), 2.60 (m, 12H, 4 CH3), 5.00 (s, 4H,
2 CH2), 5.10 (s, 4H, 2 CH2), 7.20 (m, 10H, 4 pyrrole-H,
6 -CH=), 13.20–13.40 (m, 12H, 12 NH). FAB-MS (matrix:
3-NBA) m/z: 1308 ([M+ + 2]). HR-MS (LSIMS, thioglycerol)
for C84H99N12S calcd.: 1307.78364; found: 1307.78342.
In summary, we have developed a fast, highly efficient
synthetic methodology that appears to be of versatile utility
in terms of allowing for the construction of linear
polypyrromethenes. The resulting compounds are stable and
exist as the corresponding hydrobromide salts. Self-
assembly of those novel ligands with transition metal ions is
currently being studied.
© 2002 NRC Canada

Chen and Dolphin
1675
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Acknowledgment
This work was supported by Natural Sciences and Engi-
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© 2002 NRC Canada