Porphyrins with exocyclic rings. Part 23: Synthesis of porphyrins with large exocyclic rings-cyclohexadeca[b]pyrroles and porphyrins therefrom

Article abstract of DOI:10.1016/j.tet.2007.09.060

Knorr-type condensation of cyclododecanone, cyclopentadecanone, and cyclohexadecanone with phenylhydrazones derived from acetoacetate esters in the presence of zinc dust at elevated temperatures gave the corresponding large ring cycloalka[b]pyrroles in excellent yields. A cyclohexadeca[b]pyrrole was reacted with lead tetraacetate to give an acetate derivative, and this condensed with α-unsubstituted pyrroles in the presence of p-toluenesulfonic acid in acetic acid to give a series of related dipyrrolic structures. Hydrogenolysis of the benzyl ester protective groups, followed by '2+2' condensations with dipyrrylmethane dialdehydes, gave unusual cycloalkanoporphyrins with 16-membered exocyclic rings. When an alkyl group is situated next to the carbocyclic ring, proton NMR spectroscopy indicates that the conformational mobility of the carbocyclic unit is severely restricted.

Full text of DOI:10.1016/j.tet.2007.09.060

Tetrahedron 63 (2007) 12343–12351
Porphyrins with exocyclic rings. Part 23: Synthesis of porphyrins
with large exocyclic rings—cyclohexadeca[b]pyrroles
and porphyrins therefrom*
*
Timothy D. Lash, Thomas G. Marron and Jolie A. Bastian
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, USA
Received 8 October 2006; revised 24 September 2007; accepted 25 September 2007
Available online 29 September 2007
Abstract—Knorr-type condensation of cyclododecanone, cyclopentadecanone, and cyclohexadecanone with phenylhydrazones derived from
acetoacetate esters in the presence of zinc dust at elevated temperatures gave the corresponding large ring cycloalka[b]pyrroles in excellent
yields. A cyclohexadeca[b]pyrrole was reacted with lead tetraacetate to give an acetate derivative, and this condensed with a-unsubstituted
pyrroles in the presence of p-toluenesulfonic acid in acetic acid to give a series of related dipyrrolic structures. Hydrogenolysis of the benzyl
ester protective groups, followed by ‘2+2’ condensations with dipyrrylmethane dialdehydes, gave unusual cycloalkanoporphyrins with
16-membered exocyclic rings. When an alkyl group is situated next to the carbocyclic ring, proton NMR spectroscopy indicates that the
conformational mobility of the carbocyclic unit is severely restricted.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
mixtures can be used as chemical markers in petroleum
exploration4 and have been investigated for environmental
applications in monitoring the origins of oil spills.5 We
have previously explored the syntheses of natural petropor-
phyrins and related ‘type II’ isomers starting from cyclic
ketones.6,7 Knorr-type condensations of oximes or phenyl-
hydrazones with cyclohexanone, cycloheptanone, or cyclo-
octanone afford the related cycloalka[b]pyrroles 4 in good
yields,8–10 and these can be taken onto dipyrrolic intermedi-
ates 5 that represent the southern half of the CAP structures
(Scheme 1).9–11 Following the removal of the ester protec-
tive groups, the dipyrroles can be condensed with dipyrryl-
methane dialdehydes 6 in the presence of an acid catalyst
to give, following the addition of zinc acetate and air oxida-
tion, the corresponding unnatural type II porphyrins 7.9–12
These porphyrins have proven to be useful model com-
pounds in their own right,13,14 but more stepwise routes
have been developed for the synthesis of the less symmetri-
cal naturally occurring petroporphyrins.15 However, Mac-
Donald-type ‘2+2’ route to CAPs is very versatile and has
been applied to the synthesis of porphyrins with gem-dime-
thylpropano subunits16 and porphyrins with five-membered
exocyclic rings.11,12 As these straightforward procedures al-
low access to diverse CAP structures, the synthesis of more
complex systems using the same type of methodology was
considered a worthwhile goal. Given the many applications
for porphyrin based materials, ranging from catalysis17 to
supramolecular assemblies,18 molecular electronics,19 and
molecular scale data storage,20 the formation of more com-
plex CAP systems offers the potential to generate new types
Naturally Occurring Cycloalkanoporphyrins:
Me
R
Me
R
Me
R
Et
Et
Et
Me
Me
Me
Me
Me
Me
N
N
N
N
N
N
N
N
N
N
N
N
M
M
M
Me
Me
Me
R1
H
H
R2
R1
R3
3
2
1
M = Ni or VO
M = Ni or VO
R = H, Me or Et
M = Ni or VO
R = H, Me or Et
R = H, Me or Et
R1 = Me or CH2OH
R1 = H, Me, Et or Pr
R2,R3 = H or Me
Cycloalkanoporphyrins (CAPs; e.g., 1–3) are commonly
found in metalated form in organic-rich sediments such as
oil shales and petroleum.1,2 These geoporphyrins are primar-
ily derived from the photosynthetic pigments of algae and
bacteria, and can provide insights into the geological origins
of sedimentary materials.3 In addition, petroporphyrin
*
For Part 22 of this series, see: Lash, T. D.; Li, W.; Quizon-Colquitt, D. M.
Tetrahedron 2007, 63, 12324–12342.
Keywords: Porphyrin synthesis; Cycloalkenopyrroles; Pyrrole chemistry;
MacDonald reaction; Knorr condensation.
* Corresponding author. Tel.: +1 309 438 8554; fax: +1 309 438 5538;
e-mail: tdlash@ilstu.edu
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.09.060

12344
T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
of porphyrin building blocks. For instance, porphyrins
linked via this type of carbocyclic unit could act as linkers
that enforce specific angle and distance connectivities be-
tween porphyrin within a larger assembly. In order to explore
the potential of this methodology, porphyrins with large
exocyclic rings were targeted for synthesis. The ability to
form CAPs of this type would demonstrate that far more
complex linkages can be introduced starting from simple
ketone precursors.
following precipitation in ice/water and recrystallization
from ethanol, pure cyclododeca[b]pyrrole 9a was obtained
in 33–37% yield.
Me
O
(CH2)n
Zn
AcOH
CH2
(CH2)n
CH2
O
O
Me
N
NH
O
CO2R
CH2
CH2
H2N
CO2R
Ph
a. n = 9
b. n = 12
c. n = 13
8
a. R = Et
b. R = Me
c. R = Bn
(CH2)n
Me
CO2R
R1
(CH2)n
Me
CO2R
Me
Me
O
33-62%
N
H
(CH2)n
Me
CO2R
CH2
(CH2)n
CH2
NH HN
RO2C
CO2R
4
n = 2-5
CH2
N
H
5
N
H
9
(CH2)n
1. p-TSA
2. [O]
a. n = 9; R = Et; b. n = 13; R = Et;
c. n = 13; R = Me; d. n = 13; R = Bn;
e. n = 12; R = Et; f. n = 12; R = Me ; g. n = 12; R = Bn
R1
Me
Me
CHO
Me
R2
Me
OHC
NH HN
NH
N
N
Scheme 2.
Me
R2
HN
The success of this pilot study encouraged us to investigate
the use of even large rings. Cyclopentadecanone is readily
available, and 8-cyclohexadecenone is also reasonably inex-
pensive and accessible. The latter compound is easily hydro-
genated over 10% Pd/C to give cyclohexadecanone in
quantitative yields. The 16- and 15-membered ring ketones
were reacted with phenylhydrazones 8a–c under the condi-
tions developed for cyclododecanone (Scheme 2), and the
related cycloalka[b]pyrroles 9b–g were isolated in excellent
yields (40–68%). All six of these pyrroles were fully charac-
terized and were obtained as white crystals or powders.25
6
Me
R2
R2
7
Scheme 1.
2. Results and discussion
In our previous studies, we prepared cycloalka[b]pyrroles
using a variant on Knorr pyrrole condensation.6,21 In this
chemistry, an aminoketone is generated in situ by reducing
an oxime or phenylhydrazone with zinc dust in acetic acid
and this condenses with the cyclic ketone to give the required
porphyrin. Although oximes are more commonly used in
Knorr syntheses,21 phenylhydrazones give superior yields
in some cases.8–10,22 Phenylhydrazones 8 are easily prepared
by reacting benzenediazonium chloride with esters of aceto-
acetic acid,8,23 while oximes can be generated by nitrosation
of the same starting materials.6 In most Knorr-type reac-
tions, the chemistry is initiated at ca. 70–80 ꢀC, and the
zinc metal reductant and aminoketone precursor are added
simultaneously to the ketone in acetic acid while maintain-
ing the temperature at 80–100 ꢀC.24 For cyclic ketones
with six- to eight-membered rings, slightly higher tempera-
tures were employed but yields plummeted if the reaction
temperature was allowed to get too high.8–10 With these con-
cerns in mind, the same chemistry was attempted using inex-
pensive cyclododecanone and phenylhydrazone 8a derived
from ethyl acetoacetate (Scheme 2). Under conventional
conditions, no pyrrolic products could be detected and
most of the cyclic ketones could be recovered. However, if
the reaction was conducted at the boiling point of acetic
acid, trace amounts of the desired pyrrole product could be
detected by NMR spectroscopy. Although the initial results
were unexpected, they nonetheless suggested that still higher
temperatures might facilitate pyrrole formation. Propionic
acid was selected as the solvent due to its higher boiling
point. Following further investigations, the best results
were obtained using relatively dilute conditions with 3.0 g
of sodium acetate for every 10 mL of propionic acid. Tem-
peratures were maintained as high as possible during the
initial phases of the chemistry (typically 145–150 ꢀC), and
In order to access the viability of synthesizing porphyrins
with large exocyclic rings, cyclohexadeca[b]pyrrole 9d was
reacted with lead tetraacetate in 1:1 v/v acetic acid/dichloro-
methane to give the 17-acetoxy derivative 10 (Scheme 3).
The acetate was subsequently reacted with a-unsubstituted
pyrroles 11a–c to give the novel dipyrroles 12a–c in 52–
71% yield. These reactions proceeded without any compli-
cations, although the NMR spectra were complex due to
Me
N
BnO2C
H
9d
Pb(OAc)4
Me
OAc
10
N
BnO2C
H
H+
Me
CO2Bn
R
H
N
H
R
11
a. R = H
b. R = Me
c. R = Et
Me
Me
N
N
H
H
CO2Bn
BnO2C
12 a. R = H; b. R = Me; c. R = Et
Scheme 3.

T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
12345
the presence of a chiral center and the large number of chem-
ically similar methylene subunits. The bridging CH unit in
the b-unsubstituted product 12a was observed as a triplet
at 4.0 ppm, while the b-substituted dipyrroles showed this
resonance further downfield at 4.19 ppm. Hydrogenolysis
of the benzyl ester protective groups was easily accom-
plished over 10% Pd/C and the resulting dicarboxylic acids
13a–c were then used to synthesize porphyrins with 16-
membered exocyclic rings (Scheme 4).
porphyrins 14a and 14b gave a series of five 2H multiplets
between 1.8 and 2.6 ppm, a 4H multiplet at 1.7–1.8 ppm,
and a 10H multiplet near 1.5 ppm, while the meso-CH2
gave a 2H multiplet at nearly 5.0 ppm and the b-methylene
gave a 2H multiplet near 4.0 ppm. These data essentially
fall into the expected region for substituents attached to
a porphyrin ring system, and indicate that the carbocyclic
ring does not significantly fold back over the p-system.
The equivalent signals for the fully b-substituted porphy-
rins 14c and 14d showed significant differences, and the
resonances for the methylene units not directly connected
to the porphyrin system did not extend beyond 2.3 ppm.
In addition, at 25 ꢀC the meso-CH2 unit gave rise to two
separate 1H resonances at 4.9 and 5.2 ppm indicating
that steric crowding from the b-substituent introduces a sig-
nificant restriction to the conformational mobility of the
16-membered ring. However, these broadened resonances
coalesced as the temperature was raised to 50 ꢀC
(Fig. 1). Addition of a drop of TFA to the NMR tubes
gave the related dications 14H22+ and the resulting NMR
spectra were also well resolved and confirmed the dia-
tropic character. The four internal NHs gave rise to four
well separated resonances in these spectra, indicating
that there must be significant differences in their chemical
environment. The carbocyclic ring protons also showed
significantly different shifts, and in particular the meso-
CH2 unit for 14cH22+ and 14dH22+ no longer showed the
presence of diastereotopic protons. The meso-protons for
the dications of 14a and 14b showed a downfield shift
of 0.4–0.5 ppm, affording three resonances between
10.3 and 10.6 ppm; however, the b-pyrrolic proton shifted
upfield by ca. 0.2 ppm to give singlets at 9.09 and
9.07 ppm, respectively. Porphyrin dications generally
show an increased diatropic ring current,28 but any assess-
ment of the diatropic character must take into account the
associated positive charges. The latter effect should result
in some deshielding, even though the b-proton is shifted
upfield. The meso-protons for 14cH22+ and 14dH22+ are de-
shielded compared to the free base forms, but the effect is
smaller than the one observed for 14aH22+ and 14bH22+ re-
sulting in shifts of only 0.2–0.3 ppm with three 1H singlets
showing up between 10.05 and 10.25 ppm. The alkyl sub-
stituents on the porphyrin macrocycle can give a good in-
dication of the ring current without significant perturbation
by the dicationic character.29 For 14aH22+ and 14bH22+, the
methyl resonances fell into the range of 3.43–3.61 ppm
compared to value of 3.57–3.72 for the free base porphy-
rins. The upfield shifts for 14cH22+ and 14dH22+ were
even more significant, giving a series of singlets in the
range of 3.28–3.49 compared to 3.59–3.62 in the free
base compounds. Taken together, these data indicate that
the diatropicity is reduced in the dications, particularly
in the cases of 14c and 14d, and this is probably due to
the relief of steric interactions that are exacerbated by
the presence of four hydrogen atoms in the macrocyclic
cavity. Distortion of the porphyrin nucleus appears to re-
duce the crowding between the ring and the adjacent alkyl
substituent in 14c and 14d, thereby allowing increased mo-
bility to the carbocyclic unit. Carbon-13 NMR data for
porphyrins 14a–d in TFA/CDCl3 showed the three unsub-
stituted meso-carbons at typical values30 between 94.7 and
98.9 ppm, while the substituted meso-carbon was observed
near 126 ppm.
R1
R1
R1
R1
Me
CHO
Me
Me
Me
Me
Me
NH HN
a. R1 = Et; b. R = PMe
N
N
N
N
H
OHC
6
1. p-TSA
H
2. O2-Zn(OAc)2
CO2H
HO2C
H
H
N
N
Me
Me
R
R
14
13
a. R = H; R1 = Et b. R = H; R1 = PMe
c. R = Me; R1 = Et d. R = R1 = Et
a. R = H; b. R = Me; c. R = Et
PMe = CH2CH2CO2Me
Scheme 4.
Using MacDonald ‘2+2’ methodology,26 dipyrrole 13a was
reacted with dipyrrylmethane 6a or 6b in the presence of
p-toluenesulfonic acid (Scheme 4). Following the addition
of excess zinc acetate, the reaction mixture was allowed to
air oxidize for 2 days. These mild conditions have been
used to prepare porphyrins with five-, six-, seven- or eight-
membered exocyclic rings previously.8–12 However, the con-
formation of the intermediates can be a significant factor in
the efficiency of these cyclizations10 and the effect of large
rings on these reactions was not known. In the event, good
yields of the porphyrin products 14a and 14b could be iso-
lated following chromatography and recrystallization from
chloroform/methanol. In addition, similar results were ob-
tained when dipyrroles 13b and 13c were reacted with 6a un-
der the same conditions. Porphyrins 14a–d were fully
characterized by UV–vis, proton NMR and carbon-13
NMR spectroscopies, mass spectrometry, and combustion
analysis. Porphyrins gave the expected phyllo-type UV–vis
spectra27 in chloroform with Soret bands at 407–408 nm.
Addition of TFA generated the corresponding dications
14H22+ where Soret band shifts to 414–416 nm for 14a and
14b, and 417–418 nm for 14c and 14d. The slightly larger
bathochromic shifts observed for the two porphyrins 14c,d
with alkyl groups next to the carbocyclic ring may be due
to the steric crowding leading to a minor distortion to the
chromophore (see below).
The proton NMR data for the new porphyrins in CDCl3
showed that the large exocyclic ring did not significantly
affect the diatropic character for the macrocycle, and the
meso-protons were observed at typical downfield values
in the range of 9.78–10.06 ppm. The b-pyrrolic proton in
14a or 14b was also evident at 9.24 ppm, while the inter-
nal NHs gave upfield resonances between ꢁ2.8 and
ꢁ3.2 ppm. The carbocyclic ring for the b-unsubstituted

12346
T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
Figure 1. Partial 400 MHz proton NMR spectrum of meso-b-tridecanoporphyrin 14c in CDCl3 at 25 ꢀC showing two broad resonances for the diastereotopic
meso-CH2 unit. Inset A: spectrum at 35 ꢀC; inset B: spectrum at 50 ꢀC showing coalescence of the methylene resonances.
3. Conclusions
III neutral alumina (6 mL H2O for 100 g grade I alumina)
or 70–230 mesh silica gel; grade III silica was prepared by
shaking 100 g SiO2 with 10 mL of water. Melting points
were determined in open capillary tubes on a Mel-Temp
apparatus and are uncorrected. IR spectra were recorded
on a Perkin–Elmer 1600 Series FT-IR Spectrometer and
only selected absorptions (in reciprocal centimeters) are
listed, while UV–vis absorption spectra were run on a
Beckmann DU-40 spectrophotometer or a Varian Cary
Spectrophotometer. Proton and carbon-13 NMR data were
obtained on Varian Gemini 300 or 400 MHz FT-NMR Spec-
trometers. Mass spectral determinations were conducted at
the Mass Spectral Laboratory, School of Chemical Sciences,
University of Illinois at Urbana-Champaign. Elemental anal-
yses were obtained from Micro-Analysis, Inc., Wilmington,
DE 19808, or the School of Chemical Sciences Microanaly-
sis Laboratory at the University of Illinois.
A series of pyrroles fused to large carbocyclic rings are
easily prepared from cyclic ketones using Knorr-type
chemistry. A cyclohexadeca[b]pyrrole prepared by this
methodology was used to prepare dipyrrolic intermediates
that incorporate the fused carbocyclic ring. Following depro-
tection of the benzyl esters, these dipyrroles reacted with
dipyrrylmethane dialdehydes under MacDonald ‘2+2’ con-
ditions to afford novel porphyrins with tridecano-bridges.
The fused 16-membered rings appear to cause minor dis-
tortion to the porphyrin macrocycle due to steric crowding
and this effect was exacerbated by a proximal alkyl substit-
uent. Nevertheless, these results indicate that cycloalka[b]-
pyrroles can be used to synthesize complex porphyrin
systems.
4. Experimental
4.1. General
4.2. Synthetic procedures
4.2.1. Cyclohexadecanone. A solution of 8-cyclohexadece-
none (20.0 g) in acetone (150 mL) was shaken with 10% pal-
ladium/charcoal (200 mg) under a hydrogen atmosphere at
room temperature and 30 psi for 90 min. The catalyst was
removed by suction filtration and the solvent evaporated
under reduced pressure to give the cyclic ketone (20.0 g,
quantitative) as colorless crystals, mp 63–64 ꢀC (lit. mp
56 ꢀC,31a 62–63.5 ꢀC,31b 60 ꢀC31c); IR (Nujol mull): nC]O
Ethyl acetoacetate, methyl acetoacetate, 8-cyclohexadece-
none, cyclopentadecanone, cyclododecanone, lead tetra-
acetate, triethylamine, and p-toluenesulfonic acid were
purchased from Aldrich or Acros, and were used without fur-
ther purification. Benzyl acetoacetate was purchased from
TCI America. Chromatography was performed using grade

T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
12347
1714 cmꢁ1; 1H NMR (CDCl3): d 1.26–1.31 (22H, m), 1.63
(4H, quintet, J¼6.8 Hz), 2.40 (4H, t, J¼6.6 Hz); 13C NMR
(CDCl3): d 23.7, 28.8 (3), 27.2, 27.4, 27.9, 42.2, 212.5.
under the foregoing conditions. Recrystallization from hex-
anes gave benzyl ester (2.05 g, 5.03 mmol, 40%) as white
crystals, mp 171–171.5 ꢀC; IR (Nujol mull): n 3294 (NH
1
str.), 1661 (C]O str.) cmꢁ1; H NMR (CDCl3): d 1.2–
4.2.2. Ethyl 3-methylcyclohexadeca[b]pyrrole-2-carb-
oxylate (9a). A mixture of cyclohexadecanonone (3.00 g,
12.6 mmol), sodium acetate (18.0 g), and propionic acid
(60 mL) was placed in a 500 mL Erlenmeyer flask and
heated to 140 ꢀC on an oil bath. A solution of phenylhydr-
azone 8a8,23 (3.14 g, 13.4 mmol) in propionic acid (60 mL)
was added to the mixture while simultaneously adding
zinc dust (10 g) in small portions over a period of 1 h, main-
taining the temperature of the reaction above 150 ꢀC. Once
the addition was complete, the mixture was stirred for 1 h
at 120–140 ꢀC. The mixture was cooled to 70 ꢀC and poured
into ice/water (600 mL). The precipitate was filtered,
washed with water, and recrystallized from ethanol to give
the title compound (2.78 g, 8.01 mmol, 63%) as white crys-
tals, mp 139–140 ꢀC; IR (Nujol mull): n 3297 (s, NH str.),
1.45 (22H, m), 1.5–1.65 (2H, m), 2.27 (3H, s), 2.34 (2H, t,
J¼7 Hz), 2.50 (2H, t, J¼7 Hz), 5.28 (2H, s), 7.3–7.45 (5H,
m), 8.56 (1H, s); 13C NMR (CDCl3): d 11.0, 24.6, 25.7,
26.4, 26.6, 26.7, 26.8, 27.0, 27.7, 27.9, 28.1, 29.4, 30.2,
65.6, 116.9, 122.5, 127.7, 128.2, 128.3, 128.7, 134.9,
137.0, 161.6. Anal. Calcd for C27H39NO2: C, 79.17; H,
9.60; N, 3.42. Found: C, 78.68; H, 9.82; N, 3.69.
4.2.6. Ethyl 3-methylcyclopentadeca[b]pyrrole-2-carb-
oxylate (9e). Cyclopentadecanone (1.00 g, 4.46 mmol) and
phenylhydrazone 8a8,23 (1.10 g, 4.62 mmol) were reacted
under the foregoing conditions. Recrystallization from etha-
nol gave cyclopentadeca[b]pyrrole (0.742 g, 2.23 mmol,
50%) as white crystals, mp 139.5–140 ꢀC; IR (Nujol
1
mull): n 3306 (NH str.), 1665 (C]O str.) cmꢁ1; H NMR
1
1657 (s, C]O str.) cmꢁ1; H NMR (CDCl3): d 1.25–1.32
(CDCl3): d 1.25–1.50 (20H, m), 1.35 (3H, triplet overlap-
ping with previous multiplet), 1.58–1.67 (2H, m), 2.27
(3H, s), 2.34 (2H, t, J¼7.5 Hz), 2.52 (2H, t, J¼8 Hz), 4.30
(2H, q, J¼7.2 Hz), 8.85 (1H, br s); 13C NMR (CDCl3):
d 10.7, 14.8, 24.2, 25.6, 25.9, 26.1, 26.2, 26.3, 27.0, 27.1,
27.3, 27.5, 27.7, 28.6, 29.8, 59.7, 117.0, 122.2, 127.2,
134.7, 162.1. Anal. Calcd for C21H35NO2: C, 75.63; H,
10.58; N, 4.20. Found: C, 76.09; H, 10.12; N, 4.37.
(8H, m), 1.32–1.45 (14H, m), 1.34 (3H, t, J¼7 Hz), 1.55–
1.60 (2H, m), 2.27 (3H, s), 2.35 (2H, t, J¼7.4 Hz), 2.52
(2H, t, J¼8 Hz), 4.29 (2H, q, J¼7.2 Hz), 8.59 (1H, br s);
13C NMR (CDCl3): d 10.9, 14.8, 24.6, 25.6 (2), 26.4, 26.5,
26.6, 26.7, 27.0, 27.7, 27.9, 28.0, 28.1, 29.4, 30.5, 59.8,
117.3, 122.3, 127.1, 134.5, 162.0. Anal. Calcd for
C22H37NO2: C, 76.03; H, 10.73; N, 4.03. Found: C, 75.75;
H, 11.13; N, 4.28.
4.2.7. Methyl 3-methylcyclopentadeca[b]pyrrole-2-carb-
oxylate (9f). Cyclopentadecanone (1.00 g, 4.46 mmol) and
phenylhydrazone 8b8 (1.11 g, 5.04 mmol) were reacted
under the foregoing conditions. Recrystallization from etha-
nol gave pyrrole ester (0.97 g, 3.04 mmol, 68%) as white
crystals, mp 150–150.5 ꢀC; IR (Nujol): n 3310 (s, NH str.),
4.2.3. Ethyl 3-methylcyclododeca[b]pyrrole-2-carboxyl-
ate (9b). Cyclododecanone (9.10 g, 50.0 mmol) and phenyl-
hydrazone 8a8,23 (11.70 g, 50.0 mmol) were reacted under
the foregoing conditions. Recrystallization from ethanol
gave cyclododeca[b]pyrrole (5.46 g, 18.7 mmol, 37%) as
white crystals, mp 156–157 ꢀC; IR (Nujol mull): n 3301 (s,
1
1665 (s, C]O str.) cmꢁ1; H NMR (CDCl3): d 1.25–1.50
NH str.), 1657 (s, C]O str.) cmꢁ1
;
1H NMR (CDCl3):
(20H, m), 1.58–1.67 (2H, m), 2.27 (3H, s), 2.34 (2H, t,
J¼7.5 Hz), 2.52 (2H, t, J¼8 Hz), 3.82 (3H, s), 8.74 (1H,
br s); 13C NMR (CDCl3): d 10.7, 24.2, 25.6, 25.9, 26.0,
26.2, 26.3, 27.0, 27.1, 27.3, 27.4, 27.7, 28.6, 29.7, 51.0,
116.7, 122.3, 127.4, 134.8, 162.4. Anal. Calcd for
C20H33NO2: C, 75.19; H, 10.31; N, 4.38. Found: C, 75.61;
H, 10.23; N, 4.16.
d 1.21–1.28 (2H, m), 1.31–1.39 (6H, m), 1.35 (3H, t,
J¼7 Hz), 1.40–1.48 (4H, m), 1.56–1.63 (2H, m), 1.66–
1.74 (2H, m), 2.28 (3H, s), 2.41 (2H, t, J¼7.2 Hz), 2.55
(2H, t, J¼7.4 Hz), 4.29 (2H, q, J¼7.2 Hz), 8.60 (1H, br s);
13C NMR (CDCl3): d 11.1, 14.8, 21.4, 22.6, 22.8, 23.2,
24.4, 25.3, 25.4, 27.8, 28.2, 59.8, 117.8, 122.4, 127.2,
134.9, 162.0. Anal. Calcd for C18H29NO2: C, 74.18; H,
10.03; N, 4.81. Found: C, 74.18; H, 10.26; N, 5.01.
4.2.8. Benzyl 3-methylcyclopentadeca[b]pyrrole-2-carb-
oxylate (9g). Cyclopentadecanone (1.00 g, 4.46 mmol) and
phenylhydrazone 8c9c,23e (1.34 g, 4.53 mmol) were reacted
as previously. Recrystallization from ethanol gave 9g
(0.758 g, 1.92 mmol, 43%) as white crystals, mp 157.5–
158 ꢀC IR (Nujol): n 3307 (s, NH str.), 1669 (s, C]O
str.) cmꢁ1; 1H NMR (CDCl3): d 1.25–1.50 (20H, m), 1.58–
1.67 (2H, m), 2.30 (3H, s), 2.35 (2H, t, J¼7 Hz), 2.52 (2H,
t, J¼8 Hz), 5.31 (2H, s), 7.32–7.45 (5H, m), 8.73 (1H, s);
13C NMR (CDCl3): d 10.9, 24.2, 25.6, 25.9, 26.1, 26.2,
26.4, 27.0, 27.1, 27.3, 27.4, 27.7, 28.3, 29.7, 65.6, 116.6,
122.5, 127.8, 128.2, 128.3, 128.7, 135.0, 137.0, 161.6.
Anal. Calcd for C26H37NO2: C, 78.94; H, 9.43; N, 3.54.
Found: C, 78.92; H, 9.37; N, 3.24.
4.2.4. Methyl 3-methylcyclohexadeca[b]pyrrole-2-carb-
oxylate (9c). Cyclohexadecanone (3.00 g, 12.6 mmol) and
phenylhydrazone 8b8 (2.77 g, 12.6 mmol) were reacted un-
der the foregoing conditions. Recrystallization from ethanol
gave cyclohexadeca[b]pyrrole (2.59 g, 7.77 mmol, 62%) as
white crystals, mp 141–142 ꢀC; IR (Nujol mull): n 3310 (s,
NH str.), 1668 (s, C]O str.) cmꢁ1 1H NMR (CDCl3):
;
d 1.2–1.5 (22H, m), 1.50–1.63 (2H, m), 2.27 (3H, s), 2.35
(2H, t, J¼7 Hz), 2.52 (2H, t, J¼8 Hz), 3.82 (3H, s), 8.83
(1H, br s); 13C NMR (CDCl3): d 10.8, 24.6, 25.5, 26.3,
26.4, 26.6, 26.7, 26.9, 27.7, 27.9, 28.0, 28.1, 29.4, 30.5,
51.0, 117.0, 122.3, 127.2, 134.8, 162.5. Anal. Calcd for
C21H35NO2: C, 75.63; H, 10.58; N, 4.20. Found: C, 75.88;
H, 10.35; N, 4.23.
4.2.9. Benzyl 17-acetoxy-3-methylcyclohexadeca[b]pyr-
role-2-carboxylate (10). In an oven dried 1 L round bottom
flask fitted with a calcium chloride drying tube, benzyl 3-
methylcyclohexadeca[b]pyrrole-2-carboxylate (9d, 5.00 g,
12.2 mmol) was placed in a mixture of dichloromethane
4.2.5. Benzyl 3-methylcyclohexadeca[b]pyrrole-2-carb-
oxylate (9d). Cyclohexadecanone (3.02 g, 12.7 mmol) and
phenylhydrazone 8c9c,23e (3.85 g, 13.0 mmol) were reacted

12348
T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
(330 mL) and glacial acetic acid (330 mL). Lead tetraacetate
(95%, 5.68 g, 12.2 mmol) was added over several minutes.
After stirring overnight, the mixture was poured into water
(200 mL). The organic phase was washed with saturated
sodium bicarbonate solution, then with water, dried over
sodium sulfate, filtered, and evaporated under reduced pres-
sure. The residue was recrystallized with petroleum ether
(60–80ꢀ) to yield the acetoxy pyrrole as white crystals
(4.766 g, 10.2 mmol, 84%), mp 85.5–86.5 ꢀC; IR (Nujol
mull): n 3319 (NH str.), 1736 (acetoxy C]O str.), 1668 (pyr-
carboxylate (12c). Prepared from 10 (0.961 g, 2.06 mmol)
and benzyl 4-ethyl-3-methylpyrrole-2-carboxylate33,34 (11c,
0.500 g, 2.06 mmol) by the procedure detailed for 12a.
Recrystallization from hexanes afforded the dipyrrole as
white crystals (0.753 g, 1.16 mmol, 56%), mp 136.5–
137.5 ꢀC; IR (Nujol mull): n 3357 (NH str.), 1686 (C]O
str.), 1644 (C]O str.) cmꢁ1 1H NMR (CDCl3): d 1.00
;
(3H, t, J¼7 Hz), 1.15–1.6 (22H, m), 2.0–2.2 (2H, m),
2.24 (6H, s), 2.4–2.55 (4H, m), 4.19 (1H, t, J¼7 Hz),
5.16–5.23 (4H, m), 7.20–7.30 (10H, m), 9.87 (1H, br
s), 10.06 (1H, br s); 13C NMR (CDCl3): d 11.0, 11.2,
15.8, 17.7, 24.6, 25.4, 25.5, 26.2, 26.6, 26.7, 26.9,
27.8, 28.1, 28.3, 30.7, 33.6, 34.0, 66.0, 66.1, 118.0,
122.2, 124.5, 127.8, 127.9, 128.1, 128.4, 128.6, 134.4,
135.4, 136.5, 162.2, 162.4. Anal. Calcd for C42H54N2O4:
C, 77.50; H, 8.36; N, 4.30. Found: C, 77.42; H, 8.38;
N, 4.48.
1
role ester C]O str.) cmꢁ1; H NMR (CDCl3): d 1.1–1.55
(22H, m), 1.72–1.95 (2H, m), 2.00 (3H, s), 2.26 (3H, s),
2.46–2.53 (2H, m), 5.32 (2H, s), 5.84 (1H, dd, J¼6.0,
8.2 Hz), 7.3–7.44 (5H, m), 8.91 (1H, br s); 13C NMR
(CDCl3): d 10.8, 21.2, 24.3, 24.4, 25.3, 26.3, 26.5, 26.9,
27.6, 28.0, 28.2, 30.6, 34.4, 65.9, 68.0, 118.8, 124.0,
126.9, 128.3, 128.7, 131.9, 136.6, 161.8, 170.2. Anal. Calcd
for C29H41NO4: C, 74.48; H, 8.84; N, 2.99. Found: C, 74.37;
H, 8.59; N, 3.00.
4.2.13. (5-Carboxy-3-methyl-2-pyrrolyl)-3-methylcyclo-
hexadeca[b]pyrrole-2-carboxylic acid (13a). Dibenzyl
ester 12a (502 mg, 0.807 mmol) was dissolved in methanol
(200 mL) in a hydrogenation vessel. Triethylamine of 10
drops was added and the solution was purged with nitrogen.
Palladium/charcoal (10%, 100 mg) was rinsed with a small
amount of methanol, and the reaction vessel was shaken
under an atmosphere of hydrogen (w40 psi) overnight. The
catalyst was filtered off, and the solvent was evaporated
under reduced pressure while maintaining the temperature
below 40 ꢀC. The residue was taken up in 5% ammonia
solution, and the catalyst was washed with 5% ammonia to
dissolve any remaining product. The combined aqueous
solutions were cooled to 0 ꢀC in a salt/ice bath and neutral-
ized to litmus with glacial acetic acid. After standing at 0 ꢀC
for 1 h, the precipitate was filtered, washed with liberal
amounts of water, and dried in vacuo. The product was
isolated as pink crystals (326 mg, 0.738 mmol, 91%), mp
4.2.10. Benzyl 17-(5-benzyloxycarbonyl-3-methyl-2-pyr-
rolyl)-3-methylcyclohexadeca[b]pyrrole-2-carboxylate
(12a). Acetoxycyclohexadeca[b]pyrrole 10 (2.16 g, 4.62 mmol)
and benzyl 3-methylpyrrole-2-carboxylate32 (11a, 1.00 g,
4.65 mmol) were dissolved in glacial acetic acid (40 mL).
p-Toluenesulfonic acid (100 mg) was added immediately, and
the mixture was stirred overnight at room temperature. The
solution was poured over an ice/water slurry (500 mL) and
allowed to stand for 1 h. The precipitate was filtered and recrys-
tallized from hexanes to give the title dipyrrole as white crystals
(1.53 g, 2.46 mmol, 53%), mp 173.5–174 ꢀC; IR (Nujol mull):
n 3349 (NH str.), 3301 (NH str.), 1693 (C]O str.), 1635 (C]O
1
str.) cmꢁ1; H NMR (CDCl3): d 1.1–1.5 (22H, m), 1.83–2.05
(2H, m), 2.24 (3H, s), 2.28 (3H, s), 2.3–2.5 (2H, m), 4.00
(1H, t, J¼7.4 Hz), 5.21–5.23 (4H, m), 5.92 (1H, d, J¼
2.4 Hz), 7.23–7.36 (10H, m), 9.07 (1H, br s), 9.16 (1H, br s);
13C NMR (CDCl3): d 11.2, 13.4, 24.6, 25.4, 25.6, 26.2, 26.6,
26.7, 26.9, 28.0, 28.2, 30.6, 34.0, 36.2, 65.89, 65.94, 110.6,
118.1, 118.5, 122.8, 127.6, 128.2, 128.7, 129.4, 134.4, 136.6,
136.7, 137.7, 161.8, 162.0. Anal. Calcd for C40H50N2O4: C,
77.14; H, 8.09; N, 4.50. Found: C, 76.73; H, 8.25; N, 4.60.
1
95 ꢀC, dec; H NMR (CDCl3): d 1.2–1.5 (22H, m), 1.64
(2H, quintet, J¼6.8 Hz), 1.8–2.2 (2H, m), 2.25 (3H, s),
2.28 (3H, s), 2.4–2.5 (2H, m), 4.10 (1H, t, J¼8 Hz), 5.92
(1H, s), 10.99 (1H, br s), 11.14 (1H, br s). Anal. Calcd for
C26H38N2O4: C, 70.56; H, 8.65; N, 6.33. Found: C, 70.88;
H, 9.01; N, 6.25.
4.2.11. Benzyl 17-(5-benzyloxycarbonyl-3,4-dimethyl-2-
pyrrolyl)-3-methylcyclohexadeca[b]pyrrole-2-carboxyl-
ate (12b). Acetoxycyclohexadeca[b]pyrrole 10 (1.00 g,
2.14 mmol) and benzyl 3,4-dimethylpyrrole-2-carboxyl-
ate33 (11b, 0.515 g, 2.25 mmol) were reacted under the fore-
going conditions. Recrystallization from hexanes gave the
title dipyrrole as white crystals (0.963 g, 1.51 mmol, 71%),
mp 125–126 ꢀC; IR (Nujol mull): n 3348 (NH str.), 1689
4.2.14. (5-Carboxy-3,4-dimethyl-2-pyrrolyl)-3-methyl-
cyclohexadeca[b]pyrrole-2-carboxylic acid (13b). Dicarb-
oxylic acid was prepared from 12b (500 mg, 0.79 mmol)
with 10% palladium/charcoal (50 mg) as a catalyst as de-
scribed above. The title compound was isolated as a pink
solid (360 mg, 0.79 mmol, 100%), mp 118 ꢀC, dec; 1H
NMR (CDCl3): d 1.1–1.6 (22H, m), 1.8–2.0 (2H, m), 2.02
(3H, s), 2.22 (3H, s), 2.25 (3H, s), 2.4–2.55 (2H, m), 4.18
(1H, br t), 11.2 (2H, br s).
(C]O str.), 1651 (C]O str.) cmꢁ1 1H NMR (CDCl3):
;
d 1.15–1.55 (22H, m), 1.98 (3H, s), 2.0–2.2 (2H, m), 2.21
(3H, s), 2.23 (3H, s), 2.37–2.52 (2H, m), 4.19 (1H, t,
J¼7 Hz), 5.16–5.21 (4H, m), 7.15–7.30 (10H, m), 9.88
(1H, br s), 9.97 (1H, br s); 13C NMR (CDCl3): d 9.3, 11.2,
11.3, 24.6, 25.4, 25.6, 26.2, 26.7, 27.0, 27.7, 28.0, 28.3,
30.7, 33.1, 34.1, 66.0, 117.6, 117.8, 118.0, 122.3, 127.9,
128.1, 128.3, 128.6, 134.8, 135.4, 136.5, 162.3. Anal. Calcd
for C41H52N2O4: C, 77.32; H, 8.23; N, 4.40. Found: C,
76.79; H, 8.21; N, 4.38.
4.2.15. (5-Carboxy-4-ethyl-3-methyl-2-pyrrolyl)-3-meth-
ylcyclohexadeca[b]pyrrole-2-carboxylic acid (13c). Di-
carboxylic acid was prepared from 12c (300 mg,
0.461 mmol) by the procedure described previously. The
title dipyrrole was isolated as pink powder (196 mg,
1
0.417 mmol, 90%), mp 114 ꢀC, dec; H NMR (CDCl3):
d 1.0–1.6 (22H, m), 1.9–2.1 (2H, m), 2.26 (6H, s), 2.4–2.6
(4H, m), 4.17 (1H, br t), 11.15 (1H, br s), 11.30 (1H, br s).
Anal. Calcd for C28H42N2O4$H2O: C, 68.82; H, 9.07; N,
5.73. Found: C, 69.12; H, 8.98; N, 6.08.
4.2.12. Benzyl 17-(5-benzyloxycarbonyl-4-ethyl-3-meth-
yl-2-pyrrolyl)-3-methylcyclohexadeca[b]pyrrole-2-

T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
12349
4.2.16. 3,5-Tridecano-13,17-diethyl-2,8,12,18-tetrame-
thylporphyrin (14a). A solution of p-toluenesulfonic acid
monohydrate (230 mg) in methanol (5 mL) was added to
a stirred solution of 13a (200 mg, 0.452 mmol) and 3,30-
diethyl-4,40-dimethyl-2,20-dipyrrylmethane-5,50-dicarbalde-
hyde9c (6a, 124 mg, 0.433 mmol) in dichloromethane
(50 mL) and methanol (5 mL). After few minutes, a deep
red-orange solution was formed. The mixture was stirred
at room temperature overnight in the dark, and a saturated
solution of zinc acetate in methanol (4.5 mL) was then
added. The resulting solution was allowed to stir in the
dark for two more days at room temperature. The mixture
was washed successively with water (100 mL), 5% hydro-
chloric acid solution (2ꢂ100 mL), 5% ammonia solution
(100 mL), and water (100 mL). The organic solution was
evaporated under reduced pressure, and the residue chro-
matographed on grade III alumina, eluting with dichloro-
methane. The colored fractions were evaporated under
reduced pressure and further purified on a grade 3 silica
gel column, eluting with toluene. The red band was collected
and recrystallized from chloroform/methanol to give the title
porphyrin as mauve crystals (61 mg, 0.101 mmol, 23%), mp
276 ꢀC, dec; UV–vis (1% Et3N/CHCl3, free base): lmax
(log10 3) 407 (5.33), 505 (4.31), 540 (4.06), 574 (4.08),
627 (3.83) nm; UV–vis (1% TFA/CHCl3, dication): lmax
(log10 3) 394 (infl, 4.89), 414 (5.57), 557 (4.35), 598 (infl,
J¼7.6 Hz), 2.00 (2H, quintet, J¼8 Hz), 2.19–2.27 (2H, m),
2.51–2.59 (2H, m), 3.24–3.30 (4H, two overlapping triplets),
3.59 (3H, s), 3.649 (3H, s), 3.654 (3H, s), 3.66 (3H, s), 3.67
(3H, s), 3.71 (3H, s), 3.96–4.01 (2H, m), 4.32 (2H, t,
J¼7.8 Hz), 4.41 (2H, t, J¼7.8 Hz), 4.92–4.97 (2H, m),
1
9.24 (1H, s), 9.86 (1H, s), 10.05 (1H, s), 10.06 (1H, s); H
NMR (TFA/CDCl3): d ꢁ3.58 (1H, s), ꢁ3.32 (1H, s),
ꢁ3.22 (1H, s), ꢁ2.55 (1H, s), 1.48–1.63 (10H, m), 1.69
(2H, quintet, J¼7 Hz), 1.76 (2H, quintet, J¼7 Hz), 1.89
(2H, quintet, J¼7.0 Hz), 2.09 (2H, quintet, J¼7.0 Hz),
2.27–2.35 (2H, m), 2.59–2.67 (2H, m), 3.10 (2H, t,
J¼7.8 Hz), 3.15 (2H, t, J¼7.8 Hz), 3.43 (3H, s), 3.57 (3H,
s), 3.59 (6H, s), 3.61 (6H, s), 3.63–3.68 (2H, m), 4.36–
4.42 (4H, two overlapping triplets), 4.89–4.94 (2H, m),
9.07 (1H, s), 10.42 (1H, s), 10.43 (1H, s), 10.56 (1H, s);
13C NMR (TFA/CDCl3): d 12.0, 12.2, 14.0, 21.7, 25.1,
26.1, 26.3, 26.7, 26.9, 27.1, 27.2, 28.8, 29.5, 30.1, 31.5,
35.54, 35.58, 39.1, 52.7, 96.9, 98.6, 98.9, 124.3, 125.5,
138.3, 139.5, 139.6, 139.7, 139.87, 139.95, 140.2, 141.1,
141.5, 141.7, 142.1, 142.3, 142.8, 143.0, 144.5, 175.0.
HRMS (EI) calcd for C45H58N4O4: 718.4458, found:
718.4465. Anal. Calcd for C45H58N4O4: C, 75.17; H, 8.13;
N, 7.79. Found: C, 75.02; H, 8.28; N, 7.82.
4.2.18. 3,5-Tridecano-13,17-diethyl-2,7,8,12,18-pentameth-
ylporphyrin (14c). The title porphyrin was prepared from
13b (100 mg, 0.219 mmol) and dipyrrylmethane dialdehyde
6a9c (60 mg, 0.210 mmol) as described previously. Recrys-
tallization from chloroform/methanol afforded the desired
porphyrin as dark maroon crystals (42 mg, 0.068 mmol,
33%), mp 270 ꢀC, dec; UV–vis (1% Et3N/CHCl3, free
base): lmax (log10 3) 407 (5.45), 507 (4.45), 540 (4.19),
575 (4.19), 627 (3.95) nm; UV–vis (1% TFA/CHCl3, dica-
tion): lmax (log10 3) 417 (5.66), 561 (4.46), 602 (4.15) nm;
1H NMR (CDCl3, 25 ꢀC): d ꢁ2.86 (2H, br s), 1.45–1.63
(10H, m), 1.65–1.71 (2H, m), 1.73–1.80 (2H, m), 1.81–
1.86 (6H, two overlapping triplets), 1.8–2.0 (4H, m), 2.27
(2H, quintet, J¼8 Hz), 3.59 (3H, s), 3.60 (3H, s), 3.61 (6H,
s), 3.62 (3H, s), 3.96–4.06 (6H, m), 4.85–5.04 (1H, m),
5.14–5.32 (1H, m), 9.80 (1H, s), 10.05 (1H, s), 10.06 (1H,
1
4.02) nm; H NMR (CDCl3): d ꢁ3.13 (2H, br s), 1.5–1.65
(10H, m), 1.70–1.81 (4H, m), 1.84 (3H, t), 1.86 (3H, t),
1.82–1.93 (2H, m), 2.21–2.29 (2H, m), 2.53–2.61 (2H, m),
3.57 (3H, s), 3.64 (3H, s), 3.66 (3H, s), 3.72 (3H, s), 3.96–
4.02 (4H, m), 4.08 (2H, q, J¼7.6 Hz), 4.95–4.99 (2H, m),
1
9.25 (1H, s), 9.86 (1H, s), 10.05 (1H, s), 10.06 (1H, s); H
NMR (TFA/CDCl3): d ꢁ3.91 (1H, s), ꢁ3.64 (1H, s),
ꢁ3.48 (1H, s), ꢁ2.80 (1H, s), 1.48–1.64 (10H, m), 1.69
(3H, t, J¼7.8 Hz), 1.74 (3H, t, J¼7.8 Hz), 1.70–1.82 (4H,
m), 1.89 (2H, quintet, J¼7.0 Hz), 2.10 (2H, quintet,
J¼7.6 Hz), 2.27–2.35 (2H, m), 2.59–2.68 (2H, m), 3.44
(3H, s), 3.56 (3H, s), 3.59 (3H, s), 3.60 (3H, s), 3.64–3.69
(2H, m), 4.01–4.09 (4H, two overlapping quartets), 4.90–
4.95 (2H, m), 9.09 (1H, s), 10.31 (1H, s), 10.44 (1H, s),
10.45 (1H, s); 13C NMR (TFA/CDCl3): d 11.82, 11.84,
12.1, 14.0, 16.2, 16.3, 20.14, 20.16, 25.1, 26.1, 26.3, 26.7,
26.9, 27.1, 27.2, 28.9, 30.1, 311.5, 35.6, 39.1, 96.0, 98.4,
98.7, 124.2, 125.5, 138.2, 138.7, 138.8, 140.0, 140.1, 141.4,
141.5, 141.8, 141.9, 142.0, 143.1, 143.3, 144.0, 144.1,
144.3. HRMS (EI) calcd for C41H54N4: 602.4348, found:
602.4349; HRMS (FAB) calcd for C41H54N4+H: 603.4430,
found: 603.4407. Anal. Calcd for C41H54N4$1/4H2O:
C, 81.07; H, 9.04; N, 9.22. Found: C, 80.84; H, 9.00; N,
9.19.
1
s); H NMR (TFA/CDCl3): d ꢁ3.60 (1H, s), ꢁ3.53 (1H,
s), ꢁ2.69 (1H, s), ꢁ2.57 (1H, s), 0.96–1.48 (12H, m), 1.67
(3H, t, J¼7.6 Hz), 1.70 (3H, t, J¼7.6 Hz), 1.73–1.83 (4H,
m), 2.04 (2H, quintet, J¼7.6 Hz), 2.15–2.24 (2H, m),
2.48–2.56 (2H, m), 3.28 (3H, s), 3.30 (3H, s), 3.32 (3H, s),
3.42–3.47 (2H, m), 3.488 (3H, s), 3.493 (3H, s), 3.97 (4H,
q, J¼7.7 Hz), 4.92–4.96 (2H, m), 10.08 (1H, s), 10.248
(1H, s), 10.253 (1H, s); 13C NMR (TFA/CDCl3): d 11.7,
12.1, 12.2, 14.6, 16.18, 16.22, 20.0, 25.0, 26.0, 26.6, 26.7,
27.0, 28.8, 29.4, 29.9, 31.3, 33.8, 38.1, 94.8, 98.12, 98.15,
126.0, 133.3, 137.0, 138.6, 138.7, 141.0, 141.4, 141.5,
141.6, 142.4, 143.0, 143.5, 143.6, 143.75, 143.78. HRMS
(FAB) calcd for C42H56N4+H: 617.4587, found: 617.4570.
Anal. Calcd for C42H56N4$1/4H2O: C, 81.18; H, 9.16; N,
9.01. Found: C, 81.00; H, 9.36; N, 9.00.
4.2.17. 3,5-Tridecano-13,17-bis-(2-methoxycarbonyl-
ethyl)-2,8,12,18-tetramethylporphyrin (14b). Dipyrrole
13a (100 mg, 0.226 mmol) was condensed with dialdehyde
6b35 (86 mg, 0.214 mmol) under the foregoing conditions.
Recrystallization from chloroform/methanol gave porphyrin
(35 mg, 0.049 mmol, 23%) as purple crystals, mp 248 ꢀC,
dec; UV–vis (1% Et3N/CHCl3, free base): lmax (log10 3)
408 (5.36), 506 (4.30), 541 (4.01), 574 (4.04), 628
(3.74) nm; UV–vis (1% TFA/CHCl3, dication): lmax
(log10 3) 396 (infl, 4.88), 416 (5.58), 559 (4.29), 598 (infl,
4.2.19. 3,5-Tridecano-7,13,17-diethyl-2,8,12,18-tetrameth-
ylporphyrin (14d). Porphyrin 14d was prepared by the
same procedure from 13c (200 mg, 0.425 mmol) and dialde-
hyde 6a9c (116 mg, 0.405 mmol). Recrystallization with
chloroform/methanol yielded the title porphyrin as dark ma-
roon crystals (75 mg, 0.12 mmol, 29%), mp 235 ꢀC, dec;
UV–vis (1% Et3N/CHCl3, free base): lmax (log10 3) 408
1
3.89) nm; H NMR (CDCl3): d ꢁ3.18 (1H, s), ꢁ3.11 (1H,
s), 1.5–1.64 (10H, m), 1.68–1.82 (4H, m), 1.88 (2H, quintet,

12350
T. D. Lash et al. / Tetrahedron 63 (2007) 12343–12351
7. (a) Lash, T. D. Org. Geochem. 1989, 14, 213; (b) Lash, T. D.;
Balasubramaniam, R. P.; Catarello, J. J.; Johnson, M. C.;
May, D. A., Jr.; Bladel, K. A.; Feeley, J. M.; Hoehner, M. C.;
Marron, T. G.; Nguyen, T. H.; Perun, T. J., Jr.; Quizon,
D. M.; Shiner, C. M.; Watson, A. Energy Fuels 1990, 4, 668;
(c) Lash, T. D.; Quizon-Colquitt, D. M.; Shiner, C. M.;
Nguyen, T. H.; Hu, Z. Energy Fuels 1993, 4, 668.
8. Lash, T. D.; Bladel, K. A.; Shiner, C. M.; Zajeski, D. L.;
Balasubramaniam, R. P. J. Org. Chem. 1992, 57, 4809.
9. (a) Lash, T. D.; Balasubramaniam, R. P. Tetrahedron Lett. 1990,
31, 7545; (b) Lash, T. D. Tetrahedron Lett. 1988, 29, 6877; (c)
Lash, T. D. Tetrahedron 1998, 54, 359.
10. (a) Lash, T. D.; Johnson, M. C. Tetrahedron Lett. 1989, 30,
5697; (b) Lash, T. D.; Perun, T. J., Jr. Tetrahedron Lett. 1987,
28, 6265; (c) Bastian, J. A.; Lash, T. D. Tetrahedron 1998,
54, 6299.
11. Lash, T. D.; Catarello, J. J. Tetrahedron 1993, 49, 4159.
12. Hu, Z.; Lash, T. D. Synlett 1994, 909.
(5.26), 507 (4.27), 541 (4.02), 576 (4.02), 628 (3.78) nm;
UV–vis (1% TFA/CHCl3, dication): lmax (log10 3) 418
(5.46), 561 (4.27), 604 (3.99) nm; 1H NMR (CDCl3,
21 ꢀC): d ꢁ2.88 (1H, br s), ꢁ2.81 (1H, br s), 1.46–1.68
(12H, m), 1.75–1.85 (2H, m), 1.79 (3H, t, J¼7.4 Hz), 1.84
(6H, t, J¼7.6 Hz), 1.9–2.0 (4H, m), 2.27 (2H, quintet,
J¼8 Hz), 3.59 (3H, s), 3.60 (3H, s), 3.61 (6H, s), 3.95–
4.07 (6H, m), 4.86–5.02 (1H, m), 5.04–5.17 (1H, m), 9.78
(1H, s), 10.04 (1H, s), 10.05 (1H, s); 1H NMR (TFA/
CDCl3): d ꢁ3.51 (2H, s), ꢁ2.57 (1H, s), ꢁ2.54 (1H, s),
1.37 (3H, t, J¼7.4 Hz), 1.45–1.65 (12H, m), 1.65–1.71
(3H, two overlapping triplets), 1.72–1.82 (4H, m), 2.02
(2H, quintet, J¼8 Hz), 2.13–2.21 (2H, m), 2.47–2.58 (2H,
m), 3.29 (6H, s), 3.42–3.48 (2H, m), 3.476 (3H, s), 3.481
(3H, s), 3.63–3.71 (2H, m), 3.95 (4H, q, J¼7.7 Hz), 4.87–
4.92 (2H, m), 10.05 (1H, s), 10.22 (1H, s), 10.23 (1H, s);
13C NMR (TFA/CDCl3): d 117, 11.8, 12.0, 15.5, 16.1,
20.0, 21.1, 24.7, 25.9, 26.4, 26.6, 26.9, 27.0, 28.8, 29.4,
29.8, 31.2, 33.6, 38.6, 94.7, 97.8, 98.3, 125.7, 136.1,
137.0, 138.7, 138.8, 141.1, 141.2, 141.6, 141.7, 142.2,
142.3, 143.6, 143.8. HRMS (FAB) calcd for C43H58N4+H:
631.4744, found: 631.4760. Anal. Calcd for C43H58N4: C,
81.85; H, 9.26; N, 8.88. Found: C, 81.74; H, 9.59; N, 8.93.
13. (a) Rankin, J. G.; Czernuszewicz, R. S.; Lash, T. D. Org.
Geochem. 1995, 23, 419; (b) Czernuszewicz, R. S.; Rankin,
J. G.; Lash, T. D. Inorg. Chem. 1996, 35, 199; (c) Rankin,
ꢀ
J. G.; Cantu, R.; Czernuszewicz, R. S.; Lash, T. D. Org.
Geochem. 1999, 30, 201.
14. (a) Freeman, D. H.; Saint Martin, D. C.; Boreham, C. J. Energy
Fuels 1993, 7, 194; (b) Laycock, J. D.; Yost, R. A.; Wang, L.;
Quirke, J. M. E. Energy Fuels 1995, 9, 1079.
Acknowledgements
15. (a) Li, W.; Lash, T. D. Tetrahedron Lett. 1998, 39, 8571; (b)
Zhang, B.; Lash, T. D. Tetrahedron Lett. 2003, 44, 7253.
16. Shiner, C. M.; Lash, T. D. Tetrahedron 2005, 61, 11628.
17. (a) Crossley, M. J.; Burn, P. L. J. Chem. Soc., Chem. Commun.
1991, 1569; (b) Wagner, R. W.; Lindsey, J. S. J. Am. Chem. Soc.
1994, 116, 9759; (c) Chou, J.-H.; Kosal, M. E.; Nalwa, H. S.;
Rakow, N. A.; Suslick, K. S. The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic:
San Diego, CA, 2000; Vol. 6, pp 43–131.
This work was supported by the Petroleum Research Fund,
administered by the American Chemical Society, and the
National Science Foundation under Grant No. CHE-
0616555.
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