6-Oxopyriphlorins

Article abstract of DOI:10.1039/c3ob41506f

Reaction of 2,6-pyridinedicarbaldehyde with a series of tripyrranes in the presence of trifluoroacetic acid, followed by oxidation of a pyriphlorin intermediate with silver(i) acetate, gave 6-oxopyriphlorins in moderate to good yields. The oxophlorin anal

Full text of DOI:10.1039/c3ob41506f

Organic &
Biomolecular Chemistry
View Article Online
View Journal | View Issue
PAPER
6-Oxopyriphlorins†
Cite this: Org. Biomol. Chem., 2013, 11,
Alexandra M. Young and Timothy D. Lash*
6841
Reaction of 2,6-pyridinedicarbaldehyde with a series of tripyrranes in the presence of trifluoroacetic acid,
followed by oxidation of a pyriphlorin intermediate with silver(I) acetate, gave 6-oxopyriphlorins in mode-
rate to good yields. The oxophlorin analogues were nonaromatic porphyrinoids that gave bright green
colored solutions. Protonation with TFA afforded species that were attributed to mono- and dicationic
structures. The proton NMR spectra in TFA–CDCl3 showed downfield shifts to the meso-protons and
upfield shifts to the interior NH resonances that indicated the presence of a weakly diatropic dicationic
species. Reaction of a 6-oxopyriphlorin with nickel(II) acetate in DMF or palladium(II) acetate in aceto-
nitrile afforded the corresponding metallo-derivatives.
Received 22nd July 2013,
Accepted 3rd September 2013
DOI: 10.1039/c3ob41506f
www.rsc.org/obc
recently, examples of pyriporphyrins (e.g. 8 and 9) have been
obtained9,10 and this system is reasonably stable so long as
meso-aryl substituents are present on each side of the pyridine
moiety. The coordination chemistry of pyriporphyrins has also
been investigated.9,11 In addition, due to increasing interest in
systems of this type, numerous examples of expanded12 and
contracted porphyrinoids13 with pyridine subunits have also
been reported in recent years.
Introduction
One approach to the modification of the porphyrin chromo-
phore involves the replacement of a pyrrole unit by another
ring system. This type of modification leads to many classes of
porphyrinoid systems, including heteroporphyrins1 and
carbaporphyrins.2–5 The insertion of a cross-conjugated ring
substantially reduces or negates the aromatic characteristics of
the macrocycle, and these changes can easily be witnessed by
the changes in the NMR and UV-visible spectra. For instance,
replacement of a pyrrole subunit with a benzene ring affords
benziporphyrins 1 that are essentially devoid of overall aro-
matic character.6,7 Initial attempts to prepare the related por-
phyrin system 2 with a pyridine subunit were unsuccessful.8
Condensation of 2,6-pyridinedicarbaldehyde (3) with tri-
pyrrane 4 in the presence of HBr gave an unstable dihydropyri-
porphyrin or pyriphlorin 5, but attempts to oxidize this system
to the fully conjugated pyriporphyrin were unsuccessful
(Scheme 1).8 When the crude intermediate was treated with
3 equiv. of p-chloranil, an oxophlorin analogue 6 was formed
in 5.9% yield. However, when 1 equiv. of p-chloranil was used,
an unstable pyriphlorin dimer 7 was generated in 4.5% yield
together with a small amount of oxopyriphlorin 6.8 More
Department of Chemistry, Illinois State University, Normal, Illinois 61790-4160,
USA. E-mail: tdlash@ilstu.edu
†Electronic supplementary information (ESI)
available. See DOI:
10.1039/c3ob41506f
Scheme 1 Synthesis of pyriphlorins and related macrocycles.
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 6841–6848 | 6841

View Article Online
Paper
Organic & Biomolecular Chemistry
porphyrinoid in the original study.8 For these reasons, we have
developed an efficient methodology for preparing this poorly
studied system.21
Results and discussion
The “3 + 1” variant on the MacDonald condensation has been
widely used in the preparation of porphyrin analogues,22
including N-confused porphyrins (NCPs).23,24 During investi-
gations into the synthesis of 2-substituted NCPs 15 by this
approach (Scheme 3), it was noted that silver(I) acetate could
be used to oxidize the initially formed N-confused phlorin 16
to give a lactam-type derivative 17.24 In addition, pyrazole-
containing phlorins 18 were similarly shown to be oxidized to
the corresponding oxophlorins 19 in the presence of silver(I)
acetate (Scheme 3).25 Based on these observations, we specu-
lated that this methodology could be used to obtain superior
yields of oxopyriphlorins 6 (Scheme 4). Tripyrranes 20a–c were
easily prepared by refluxing 2,5-diunsubstituted pyrroles 21a–c
with 2 equiv. of an acetoxymethylpyrrole 22 in refluxing acetic
acid–ethanol.26,27 Hydrogenolysis of the benzyl esters over 10%
Pd/C then afforded the corresponding dicarboxylic acids
Oxophlorins 10 are the keto tautomers of hydroxyporphyr-
ins 11 (Scheme 2).14 Interestingly, this tautomer is favored
even though the presence of a cross-conjugated carbonyl group
greatly diminishes the aromatic character of the macrocycle.15
Iron(II) complexes of oxophlorins are also implicated in heme
catabolism and the formation of biliverdin-IXα.16 Oxypyri-
porphyrins 12 are examples of robust pyridone-containing por-
phyrinoids that can be considered to be the keto-tautomers of
2-hydroxypyriporphyrins 13.6a,17–19 In this case, the keto form
is fully aromatic and only tautomer 12 is observed in solution.
Oxypyriporphyrins have been more widely investigated and
have been shown to form chelates with a number of transition
metal cations.17a,20 6-Oxopyriphlorin 6 can also be considered
to be the keto tautomer of 6-hydroxypyriporphyrin 14 and
this system is also likely to act as a macrocyclic ligand. Un-
fortunately, very little information was presented for this
Scheme 3 Silver(I) acetate promoted oxidation of phlorins to N-confused
Scheme 2 Tautomerization in oxophlorins and related systems.
6842 | Org. Biomol. Chem., 2013, 11, 6841–6848
lactams and pyrazolophlorins.
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
solution, but the “H series” version was particularly unstable
and decomposed rapidly to give a red colored solution. For
this reason, only limited characterization was carried out on
6c. The red colored decomposition product could not be
identified but it gave a distinctive UV-vis spectrum with a
strong band at 530 nm (see ESI†).
Oxopyriphlorins 6a–c gave similar proton NMR spectra that
were consistent with a non-aromatic macrocycle. For 6a, the
meso-protons gave rise to three 1H singlets at 6.21, 6.45 and
7.02 ppm (Fig. 1), while the pyridine subunit afforded two 1H
doublets of doublets at 7.81 and 8.17 ppm (J = 1.2, 7.8 Hz) and
a 1H triplet at 7.99 ppm. The internal pyrrolic NHs were
observed further downfield as two broad singlets at 9.10 and
9.56 ppm. The UV-visible spectra 6a–c gave a moderate Soret-
like band near 385 nm and a less intense absorption band
stretched between 600 and 700 nm (Fig. 2). These spectra are
similar to other nonaromatic porphyrinoids such as benzipor-
phyrin. The presence of a cross-conjugated carbonyl group was
confirmed by the presence of a peak at 1624 cm−1 in the IR
spectrum. In addition, the carbon-13 NMR spectrum gave a
resonance at 181.3 ppm that was consistent with a conjugated
ketone unit.28
Scheme 4 Synthesis of 6-oxopyriphlorins.
Protonation of 6-oxopyriphlorins 6 would be expected to
occur on the internal nitrogens. The addition of trace amounts
of TFA to a solution of 6a in CDCl3 gave proton NMR spectra
that were very broad and poorly resolved, indicating that two
or more species are in equilibrium. However, when 1 drop of
TFA was added, a new species emerged that gave a nicely
resolved proton NMR spectrum. Three NH resonances could
be observed and the meso-protons now appeared at 6.54, 7.02
and 7.50 ppm. The UV-visible spectra for 6a showed a clean
transformation to a new species with the addition of 100
equivalents of TFA (Fig. 2). A Soret-like band still appeared at
386 nm but the broad band at higher wavelengths shifted to
706 nm. Further addition of TFA gave rise to significant
changes in the UV-vis spectra and addition of 500 equiv. TFA
led to a diminution of the peak at 385 and the presence of a
4a–c.27 The unstable pyriphlorin intermediates 5 were gene-
rated by condensing 2,6-pyridinedicarbaldehyde (3) with tri-
pyrranes 4a–c in the presence of TFA. No attempts were made
to isolate the pyriphlorins but instead silver(I) acetate was
added to the reaction solutions and stirring was continued for
16 h. We were gratified to find that two of the targeted
oxidation products, 6a and 6b, were generated in good yields
(Scheme 4). Following extraction, column chromatography on
grade 3 basic alumina, and recrystallization from chloroform–
methanol, oxopyriphlorins 6a and 6b were obtained as dark
green crystals in 30–34% yield. However, when the central
pyrrole unit was unsubstituted, much poorer results were
obtained and tripyrrane 4c gave oxopyriphlorin 6c in only 12%
yield. All three compounds gave a rich vibrant green color in
Fig. 1 500 MHz proton NMR spectrum of 6-oxopyriphlorin 6a in CDCl3.
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 6841–6848 | 6843

View Article Online
Paper
Organic & Biomolecular Chemistry
monoprotonated species 23 and/or 24 would be formed
(Scheme 5), depending on whether protonation occurred on a
pyridine or pyrrolenine nitrogen. Both structures could be
stabilized by resonance delocalization of the positive charge
and it is not possible to distinguish between these two possibi-
lities with the available data. Further addition of TFA could
give dicationic species such as 25 and 26 (Scheme 5). Proto-
nation onto the carbonyl group in species 25 would allow for a
canonical form 25′ with an 18π electron delocalization pathway
and this could lead to a small macrocyclic ring current. In fact,
the chemical shifts for the meso-protons have moved further
downfield than would be expected from the effect of the posi-
tive charges on the ring system alone, and some of the NH reso-
nances have moved slightly upfield compared to the values
noted for the free base spectra (Table 1). However, further
addition of TFA leads to downfield shifts to the NH reso-
nances. Therefore, the possible presence of species like 25′ is
supported by the spectroscopic data. In the carbon-13 NMR
spectrum of 6a in TFA–CDCl3, the carbonyl resonance was
broadened and shifted upfield to 172.8 ppm, which is again
consistent with this type of structure. At higher concentrations
of acid, it is possible that triprotonated species can be gene-
rated, including the hydroxypyriporphyrin trication 27. This
Fig. 2 UV-vis spectra of oxopyriphlorin 6a in chloroform (red line, free base),
with 100 equiv. TFA (green line), with 500 equiv. TFA (blue line) and in 10%
TFA–CHCl3 (purple line).
minor band at 526 nm. In 10% TFA–chloroform, a broad band
was seen at 355 nm, together with a shoulder at 414 nm and a
very broad absorption at 683 nm (Fig. 2). Initially
Scheme 5 Mono-, di- and triprotonated oxopyriphlorins. Note: not every possible protonated species is shown and the resonance contributors are representative
rather than exhaustive.
6844 | Org. Biomol. Chem., 2013, 11, 6841–6848
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
Table 1 Chemical shifts for the meso-protons and NHs in the proton NMR
spectra for 6a–c in CDCl3 (free base) or 1 drop TFA–CDCl3. The meso-proton reso-
nances for the metalated derivatives 28a and 28b are included for comparison
Oxopyriphlorin (solvent)
11-H
16-H
21-H
NHs
6a (CDCl3)
6a (TFA–CDCl3)
6b (CDCl3)
6b (TFA–CDCl3)
6c (CDCl3)
6c (TFA–CDCl3)
28a (CDCl3)
28b (CDCl3)
7.02
7.50
6.98
7.64
7.13
7.67
7.50
7.80
6.21
6.54
6.17
7.19
6.27
6.68
7.01
7.20
6.45
7.02
6.41
6.54
6.49
7.07
7.10
7.29
9.10, 9.56
8.33, 8.58, 9.52
9.07, 9.54
8.49, 8.51, 9.44
8.97, 9.49
8.61, 8.62, 9.55
—
—
Fig. 3 UV-vis spectra of metallo-6-oxopyriphlorins in chloroform. Nickel(II)
complex 28a (red line); palladium(II) complex 28b (purple line).
685 and 749 nm (Fig. 3). The proton NMR spectrum for 28b
showed the meso-protons and the pyridine resonances further
downfield than had been observed for 28a. The meso-protons
appeared as three 1H singlets at 7.12, 7.19 and 7.78 ppm
(Table 1), while the pyridine unit gave a 1H triplet at 8.32 ppm
and two 1H doublets of doublets at 8.38 and 8.82 ppm. These
data can be interpreted to suggest that the metallo-oxopyriph-
lorins 28a and 28b have some diatropic character which is
slightly enhanced for the palladium complex, possibly due to
canonical forms such as 28′. The increased diatropicity for
28b′ can be attributed to this structure taking on a more
planar conformation, as Pd(II) is a better fit for the macrocyclic
cavity than the smaller Ni(II) cation. In the carbon-13 NMR
Scheme 6 Synthesis of metalated oxopyriphlorins.
species might also take on an 18π electron delocalization spectrum for 28a and 28b in CDCl3, the carbonyl resonances
pathway, as illustrated for canonical form 27′ (Scheme 5). showed up at 179.8 and 181.4 ppm, respectively. Palladium(II)
Metalation studies were carried out with 6a using palla- complex 28b proved to be rather unstable in solution. Both of
dium(II) and nickel(II) acetate in order to investigate the capa- the metal complexes were unstable in acid and appeared to
bility of this system as a macrocyclic ligand (Scheme 6). The demetalate or decompose in the presence of TFA. The palla-
preparation of copper(II) and zinc complexes were also dium(II) complex was especially unstable and would immedi-
attempted, but these derivatives could not be isolated. The ately turn green in acidic solutions. Proton NMR spectra
nickel(II) complex 28a was obtained in 41% yield by refluxing for this green decomposition product indicated that a mixture
6-oxopyriphlorin 6a with nickel(II) acetate in DMF for 30 min. of starting material 6a and unidentified side products were
This complex could also be prepared using chloroform as a present.
solvent and carrying out the reflux overnight, but these con-
In conclusion, a series of 6-oxopyriphlorins were obtained
ditions gave slightly lower yields than were obtained with using MacDonald-type “3 + 1” conditions, followed by oxi-
DMF. The UV-visible spectrum of the dark green nickel(II) dation with silver(I) acetate. Although two of these compounds
complex was very different from that of the starting material. A were obtained in good yields, a version with an unsubstituted
slightly red shifted Soret band was present at 407 nm and a pyrrole ring proved to be rather unstable and could only be iso-
sharper band was seen at 755 nm (Fig. 3). The proton NMR lated in 12% yield. Protonation studies indicated that several
spectrum of 28a showed that the meso-protons had shifted different cationic species are generated and the proton NMR
downfield to give three 1H singlets at 7.01, 7.10 and 7.50 ppm spectra suggested that a weakly diatropic structure had been
(Table 1). The pyridine protons were also shifted slightly down- formed. Nickel(II) and palladium(II) metal complexes were
field to give resonances between 8.2 and 8.5 ppm. The related also obtained, demonstrating that oxopyriphlorins are effective
palladium(II) complex 28b was prepared by reacting 6a with macrocyclic ligands. Although these studies were limited by
palladium(II) acetate in refluxing acetonitrile. This complex the instability of some of these compounds, it is anticipated
gave red-brown colored solutions and the UV-vis spectrum pro- that meso-substituted oxopyriphlorins will prove to be more
duced a Soret-like band at 390 nm and broad absorptions at robust in solution.
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 6841–6848 | 6845

View Article Online
Paper
Organic & Biomolecular Chemistry
removed under reduced pressure and the residue purified by
column chromatography on grade 3 basic alumina, eluting
Experimental
Melting points are uncorrected. NMR spectra were recorded with dichloromethane. The solvent was removed under
using Bruker 400 or 500 MHz NMR spectrometers, and chemi- reduced pressure and the residue recrystallized from chloro-
cal shifts are reported in parts per million (ppm) relative to form–methanol to yield 6a (32 mg, 0.067 mmol, 30%) as dark
CDCl3 (1H residual CHCl3 δ 7.26, 13C CDCl3 triplet δ 77.23). 1H blue-green crystals, mp >300 °C; UV-vis (CHCl3): λmax (log10 ε)
NMR values are reported as chemical shifts δ, relative integral, 348 (4.63), 386 (4.73), 637 nm (4.12); UV-vis (100 eq. TFA–
multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multi- CHCl3): λmax (log10 ε) 319 (4.48), 386 (4.70), 706 nm (4.23); UV-
plet; dd, doublet of doublets; br, broad peak) and coupling vis (500 eq. TFA–CHCl3): λmax (log10 ε) 382 (4.53), 526 (3.76),
constant (J). Coupling constants were taken directly from the 710 nm (4.18); UV-vis (10% TFA–CHCl3): λmax (log10 ε) 355
1
spectra. 2D experiments were performed by using standard (4.63), 683 nm (4.27); H NMR (500 MHz, CDCl3): δ 1.24–1.30
1
software. NMR assignments were made with the aid of H–1H (12H, 4 overlapping triplets, 4 × CH2CH3), 2.32 (3H, s, 19-CH3),
COSY, HSQC, DEPT-135 and nOe difference proton NMR spec- 2.61 (3H, s, 8-CH3), 2.67–2.79 (6H, 3 overlapping quartets, 3 ×
troscopy. UV-vis spectra were collected on a Cary 100 Bio spec- CH2CH3), 2.88 (2H, q, J = 7.6 Hz, 9-CH2), 6.21 (1H, s, 16-H),
3
trophotometer, and IR spectra were obtained on a Perkin 6.45 (1H, s, 21-H), 7.02 (1H, s, 11-H), 7.81 (1H, dd, J = 7.8 Hz,
Elmer Spectrum 100 FT-IR spectrometer equipped with an 4J = 1.2 Hz, 2-H), 7.99 (1H, t, J = 7.8 Hz, 3-H), 8.17 (1H, dd, 3J =
attenuated total reflectance (ATR) diamond cell. High-resolu- 7.8 Hz, 4J = 1.2 Hz, 4-H), 9.10 (1H, br s), 9.56 (1H, br s)
1
tion mass spectra (HRMS) were carried out by using a double (2 × NH); H NMR (500 MHz, 1 drop TFA–CDCl3): δ 1.19–1.32
focusing magnetic sector instrument. 1H and 13C NMR spectra (12H, 4 overlapping triplets, 4 × CH2CH3), 2.41 (3H, s, 19-CH3),
for all new compounds are reported in the ESI.†
2.61 (3H, s, 8-CH3), 2.78–2.86 (6H, 3 overlapping quartets)
(3 × CH2CH3), 2.91 (2H, q, J = 7.7 Hz, 9-CH2), 6.54 (1H, s,
16-H), 7.02 (1H, s, 21-H), 7.50 (1H, s, 11-H), 8.33–8.36 (3H,
2,5-Bis-(5-benzyloxycarbonyl-3-ethyl-4-methyl-2-
pyrrolylmethyl)-3,4-dimethyl-1H-pyrrole (20b)
overlapping singlet and 2 doublets, 2,4-H and NH), 8.49 (1H, t,
1
3,4-Dimethylpyrrole (0.39 g, 4.1 mmol) and benzyl 5-acetoxy- J = 8.0 Hz, 3-H), 8.58 (1H, br s), 9.52 (1H, br s) (2 × NH); H
methyl-3-methyl-4-ethylpyrrole-2-carboxylate (2.56 g, 8.1 mmol) NMR (500 MHz, TFA–CDCl3): δ 1.19 (3H, t, J = 7.6 Hz),
were dissolved in absolute ethanol (30 mL) and acetic acid 1.22–1.29 (9H, 3 overlapping triplets, 3 × CH2CH3), 2.38 (3H, s,
(2 mL). The mixture was flushed with nitrogen and refluxed 19-CH3), 2.59 (3H, s, 8-CH3), 2.73–2.83 (6H, 3 overlapping
overnight under nitrogen. The solution was allowed to cool to quartets) (3 × CH2CH3), 2.86 (2H, q, J = 7.7 Hz, 9-CH2), 6.42
room temperature and then further cooled in an ice bath to (1H, s, 16-H), 6.90 (1H, s, 21-H), 7.41 (1H, s, 11-H), 8.22–8.25
complete precipitation. The solution was suction filtered and (3H, 2 overlapping doublets, 2,4-H), 8.43 (1H, t, J = 7.9 Hz,
rinsed with cold ethanol to remove traces of acid and the 3-H), 8.74 (1H, br s), 9.00, 9.80 (1H, br s) (3 × NH); 13C NMR
product dried by vacuum desiccation overnight to yield the tri- (CDCl3): δ 10.0, 12.5, 15.1, 16.0, 16.5, 17.2, 17.9, 18.1, 18.3,
pyrrane dibenzyl ester 20b (1.92 g, 3.17 mmol, 78%) as an off- 18.4, 89.7, 101.8, 108.0, 126.0, 128.7, 131.6, 131.8, 132.3, 133.9,
white powder, mp 168–169.5 °C; 1H NMR (500 MHz, CDCl3): 135.2, 136.4, 139.7, 140.3, 143.9, 146.2, 150.1, 152.9, 153.0,
δ 0.97 (6H, t, J = 7.5 Hz, 2 × CH2CH3), 2.00 (6H, s, 3,4-Me), 2.25 158.4, 167.9, 181.3; 13C NMR (TFA–CDCl3): δ 10.0, 11.9, 14.0,
(6H, s, 2 × pyrrole–Me), 2.35 (4H, q, J = 7.5 Hz, 2 × CH2CH3), 14.7, 15.3, 15.9, 18.0, 18.3, 18.6, 89.2, 98.9, 110.5, 128.1, 135.3,
3.54 (4H, s, 2 × bridge CH2), 4.41 (4H, br s, 2 × OCH2), 7.02 137.61, 137.65, 137.68, 141.0, 141.7, 142.0, 144.3, 144.5, 146.8,
(4H, d, J = 6.8 Hz, 4 × o-H), 7.21–7.27 (6H, m, m,p-H), 8.73 (1H, 150.2, 150.6, 151.0, 158.3, 160.8, 172.8 (br); IR: νCO 1624 cm−1
;
br s, 1-NH), 10.95 (2H, br s, 2 × NH); 13C NMR (CDCl3): δ 9.5, HR MS (ESI): Calc. for C31H34N4O + H: 479.2811. Found:
11.2, 15.9, 17.4, 22.4, 65.5, 112.7, 117.4, 123.0, 123.3, 126.7, 479.2813.
127.0, 127.5, 128.3, 133.0, 137.2, 162.8; HR MS (EI): Calc.
for C38H43N3O4: 605.3254. Found: 605.3249. Anal. calcd for
9,18-Diethyl-8,13,14,19-tetramethyl-6-oxopyriphlorin (6b)
C38H43N3O4: C, 75.34; H, 7.15; N, 6.94. Found: C, 74.98; H, Tripyrrane dicarboxylic acid 23b (100 mg, 0.24 mmol) was
7.16; N, 6.90%.
reacted with 3 (32.0 mg, 0.24 mmol) under the foregoing con-
ditions. Following oxidation with silver(I) acetate (98 mg,
0.59 mmol), chromatography on grade 3 basic alumina and
9,13,14,18-Tetraethyl-8,19-dimethyl-6-oxopyriphlorin (6a)
Tripyrrane dicarboxylic acid 23a26,27 (100 mg, 0.22 mmol) was recrystallization from chloroform–methanol, oxopyriphlorin
stirred with TFA (1 mL) under nitrogen for 2 min. The mixture 41b (37.2 mg, 0.083 mmol, 34%) was obtained as dark blue-
was diluted with dichloromethane (99 mL) and 2,6-pyridinedi- green crystals, mp >300 °C; UV-vis (CHCl3): λmax (log10 ε) 348
carboxaldehyde 3 (30.0 mg, 0.22 mmol) was immediately (4.58), 385 (4.68), 635 nm (4.00); UV-vis (500 eq. TFA–CHCl3):
added in a single portion. The resulting solution was stirred λmax (log10 ε) 368 (4.48), 717 nm (3.13); UV-vis (1% TFA–
4 h under nitrogen, silver(I) acetate (92 mg, 0.55 mmol) was CHCl3): λmax (log10 ε) 342 (4.41), 526 (4.01), 703 nm (4.01); UV-
added, and stirring was continued overnight. The mixture was vis (10% TFA–CHCl3): λmax (log10 ε) 348 (4.58), 682 nm (4.19);
then washed with water, followed by saturated sodium bicar- 1H NMR (500 MHz, CDCl3): δ 1.25–1.28 (6H, 2 overlapping tri-
bonate (the aqueous solutions were back-extracted with chloro- plets), 2.23 (3H, s), 2.29 (3H, s), 2.31 (3H, s), 2.60 (3H, s), 2.72
form at each stage in the extractions). The solvent was (2H, q, J = 7.7 Hz), 2.87 (2H, q, J = 7.7 Hz), 6.17 (1H, s), 6.42
6846 | Org. Biomol. Chem., 2013, 11, 6841–6848
This journal is © The Royal Society of Chemistry 2013

View Article Online
Organic & Biomolecular Chemistry
Paper
(1H, s), 6.98 (1H, s), 7.78 (1H, dd, 3J = 7.8 Hz, 4J = 1.2 Hz), 7.97 water. The organic layer was separated, evaporated to dryness
3
4
(1H, t, J = 7.8 Hz), 8.16 (1H, dd, J = 7.8 Hz, J = 1.2 Hz), 9.07 and chromatographed on grade 3 basic alumina, eluting with
(1H, br s), 9.54 (1H, br s); 1H NMR (500 MHz, 1 drop TFA– dichloromethane, to give a dark brown band. The solvent was
CDCl3): δ 1.29 (3H, t, J = 7.7 Hz), 1.34 (3H, t, J = 7.7 Hz) evaporated to dryness and the residue recrystallized from
(2 × CH2CH3), 2.43 (3H, s, 14-CH3), 2.50 (3H, s, 19-CH3), 2.55 chloroform–methanol to yield the nickel(II) complex (8.1 mg,
(3H, s, 13-CH3), 2.71 (3H, s, 8-CH3), 2.87–2.96 (4H, 2 overlap- 0.015 mmol, 41%) as dark green crystals, mp >300 °C; UV-vis
ping quartets, 2 × CH2CH3), 6.72 (1H, s, 16-H), 7.19 (1H, s, (CHCl3): λmax (log10 ε) 407 (4.53), 755 nm (4.08); UV-vis (1%
1
21-H), 7.64 (1H, s, 11-H), 8.19 (1H, s, NH), 8.48–8.51 (3H over- TFA–CHCl3): λmax (log10 ε) 343 (4.47), 619 nm (3.64); H NMR
lapping singlet and 2 doublets, 2,4-H and NH), 8.60 (1H, t, J = (500 MHz, CDCl3): δ 1.29–1.35 (12H, 4 overlapping triplets,
8.0 Hz, 3-H), 9.44 (1H, s, NH); 1H NMR (500 MHz, TFA–CDCl3): 4 × CH2CH3), 2.43 (3H, s, 19-Me), 2.62 (3H, s, 8-Me), 2.86–2.93
δ 1.19 (3H, t, J = 7.6 Hz, 9-CH2CH3), 1.25 (3H, t, J = 7.7 Hz, (6H, 3 overlapping quartets), 2.95 (2H, q, J = 7.7 Hz)
18-CH2CH3), 2.32 (3H, s, 14-CH3), 2.39 (3H, s, 19-CH3), 2.45 (4 × CH2CH3), 7.01 (1H, s, 16-H), 7.10 (1H, s, 21-H), 7.50 (1H, s,
3
(3H, s, 13-CH3), 2.59 (3H, s, 8-CH3), 2.76 (2H, q, J = 7.6 Hz, 18- 11-H), 8.24 (1H, t, J = 7.5 Hz, 3-H), 8.30 (1H, dd, J = 7.7 Hz,
3
4
CH2), 2.81 (2H, q, J = 7.7 Hz, 9-CH2), 6.41 (1H, s, 16-H), 6.91 4J = 1.9 Hz, 2-H), 8.56 (1H, dd, J = 7.3 Hz, J = 1.9 Hz, 4-H);
(1H, s, 21-H), 7.40 (1H, s, 11-H), 8.23–8.27 (2H, 2 overlapping 13C NMR (CDCl3): δ 10.3, 12.0, 15.6, 16.4, 16.8, 17.2, 18.4, 18.5,
doublets, 2,4-H), 8.44 (1H, t, J = 7.8 Hz, 3-H), 8.67 (1H, br s), 18.6, 92.9, 102.3, 108.6, 126.5, 128.1, 132.69, 132.75, 134.3,
8.91 (1H, br s), 9.79 (1H, br s) (3 × NH); 13C NMR (CDCl3): 135.5, 135.6, 137.0, 137.5, 138.2, 139.2, 145.7, 146.7, 148.2,
δ 10.0, 10.3, 10.4, 12.6, 15.1, 16.4, 17.8, 18.0, 89.4, 101.9, 107.7, 148.4, 150.7, 152.5, 153.7, 179.8; HR MS (EI): Calc. for
126.0, 128.7, 131.5, 131.8, 132.3, 133.8, 134.6, 135.2, 136.3, C31H32N4NiO: 534.1930. Found: 534.1935.
139.6, 140.1, 143.9, 150.2, 152.8, 154.3, 158.5, 168.6, 181.3; 13C
NMR (TFA–CDCl3): δ 9.8, 10.1, 10.5, 11.9, 14.1, 15.4, 17.9, 18.2,
[9,13,14,18-Tetraethyl-8,19-dimethyl-6-oxypyriporphyrinato]-
palladium(II) (28b)
89.0, 98.8, 110.6, 127.9, 128.0, 134.3, 135.2, 136.4, 137.3, 137.5,
141.2, 142.4, 143.9, 144.2, 145.1, 146.7, 150.0, 151.1, 158.0,
160.8, 172.9; HR MS (ESI): Calc. for C29H30N4O + H: 451.2498.
Found: 451.2496.
Palladium(II) acetate (10 mg, 0.044 mmol) was added to a solu-
tion of 6-oxypyriporphyrin 6a (10 mg, 0.021 mmol) in aceto-
nitrile (20 mL), and the solution was refluxed with stirring
under nitrogen for 30 min. The solution was cooled, diluted
with chloroform, washed with 5% aqueous sodium bicarbon-
ate solution, and the organic layer separated and evaporated to
dryness. The residue was purified by column chromatography
on grade 3 basic alumina, eluting with chloroform, and the
product was collected as a reddish/brown band. The solvent
was evaporated to dryness affording the palladium(II) complex
(3.9 mg, 6.7 × 10−3 mmol, 32%) as dark red-purple crystals, mp
>300 °C; UV-vis (CHCl3): λmax (log10 ε) 390 (4.51), 481 (4.15),
541 (3.57), 685 (3.96), 749 nm (4.12); 1H NMR (500 MHz,
CDCl3): δ 1.36–1.44 (12H, 4 overlapping triplets, 4 × CH2CH3),
2.50 (3H, s, 19-Me), 2.75 (3H, s, 8-Me), 2.95 (2H, q, J = 7.6 Hz),
3.00–3.13 (6H, 3 overlapping quartets) (4 × CH2CH3), 7.20 (1H,
s, 16-H), 7.29 (1H, s, 21-H), 7.80 (1H, s, 11-H), 8.38 (1H, t, J =
7.6 Hz, 3-H), 8.46 (1H, dd, 3J = 7.7 Hz, 4J = 1.6 Hz, 2-H),
9,18-Diethyl-8,19-dimethyl-6-oxopyriphlorin (6c)
Tripyrrane dicarboxylic acid 23c17c (100 mg, 0.25 mmol) was
reacted with 3 (34.0 mg, 0.25 mmol) under the previous con-
dition and oxidized with silver acetate (104 mg, 0.62 mmol).
Following chromatography on grade 3 basic alumina, eluting
with dichloromethane, and evaporation of the solvent, 6c
(12.7 mg, 0.030 mmol, 12%) was obtained as a dark green
solid, mp >300 °C; 1H NMR (500 MHz, CDCl3): δ 1.26–1.30
(6H, 2 overlapping triplets), 2.33 (3H, s), 2.61 (3H, s), 2.74 (2H,
q, J = 7.6 Hz), 2.89 (2H, q, J = 7.6 Hz), 6.27 (1H, s), 6.49 (1H, s),
7.03 (1H, d, J = 4.4 Hz), 7.13 (1H, s), 7.38 (1H, d, J = 4.4 Hz),
3
4
7.85 (1H, dd, J = 7.8 Hz, J = 1.2 Hz), 8.02 (1H, t, J = 7.8 Hz),
8.18 (1H, dd, 3J = 7.8 Hz, 4J = 1.3 Hz), 8.97 (1H, br s), 9.49 (1H,
br s); 1H NMR (500 MHz, TFA–CDCl3): δ 1.22 (3H, t, J = 7.7 Hz),
1.27 (3H, t, J = 7.7 Hz), 2.43 (3H, s), 2.62 (3H, s), 2.80 (2H, q,
J = 7.7 Hz), 2.86 (2H, q, J = 7.7 Hz), 6.68 (1H, s), 7.07 (1H, s),
7.34 (1H, d, 5.3 Hz), 7.67 (1H, s), 7.74 (1H, d, J = 5.3 Hz),
8.34–8.38 (2H, 2 overlapping doublets), 8.51 (1H, t, J = 8.0 Hz),
3
4
8.86 (1H, dd, J = 7.4 Hz, J = 1.6 Hz, 4-H); 13C NMR (CDCl3):
δ 10.4, 12.7, 15.7, 16.5, 17.0, 17.5, 18.5, 18.7, 18.8, 92.3, 103.3,
109.7, 128.4, 132.3, 132.4, 134.1, 134.3, 135.3, 136.4, 136.9,
137.9, 138.2, 144.3, 145.0, 145.6, 147.3, 148.9, 150.3, 152.7,
181.4; HR MS (ESI): Calc. for C31H32N4OPd: 582.1611. Found:
582.1619.
8.61–8.62 (2H,
2 overlapping singlets), 9.55 (1H, br s);
13C NMR (CDCl3): δ 9.8, 12.3, 14.9, 16.2, 17.6, 17.8, 92.4, 101.7,
112.7, 126.1, 128.7, 130.2, 131.5, 131.8, 132.1, 134.0, 135.2,
136.2, 137.0, 139.5, 149.7, 152.6, 154.2, 158.1, 168.0, 181.5; HR
MS (ESI): Calc. for C31H34N4O + H: 423.2185. Found: 423.2180.
[9,13,14,18-Tetraethyl-8,19-dimethyl-6-oxypyriporphinato]-
nickel(II) (28a)
Acknowledgements
Nickel(II) acetate tetrahydrate (26 mg, 0.104 mmol) was added This work was supported by the National Science Foundation
to a solution of 6-oxopyriphlorin 6a (18 mg, 0.037 mmol) in under grant nos. CHE-0911699 and CHE-1212691, and the
DMF (50 mL), and stirred under reflux for 30 min. The solu- Petroleum Research Fund, administered by the American
tion was cooled, diluted with chloroform, and washed with Chemical Society.
This journal is © The Royal Society of Chemistry 2013
Org. Biomol. Chem., 2013, 11, 6841–6848 | 6847

View Article Online
Paper
Organic & Biomolecular Chemistry
D. Kim and J. L. Sessler, J. Am. Chem. Soc., 2012, 134,
4076.
References
1 (a) A. W. Johnson, in Porphyrins and Metalloporphyrins, ed. 13 (a) R. Mysliborski, L. Latos-Grazynski, L. Szterenberg and
K. M. Smith, Elsevier, Amsterdam, 1975, pp. 729–754;
(b) L. Latos-Grazynski, in The Porphyrin Handbook, ed.
K. M. Kadish, K. M. Smith and R. Guilard, Academic Press,
T. Lis, Angew. Chem., Int. Ed., 2006, 45, 3670; (b) S. Neya,
M. Suzuki, T. Matsugae and T. Hoshino, Inorg. Chem.,
2012, 51, 3891.
San Diego, 2000, vol. 2, pp. 361–416; (c) I. Gupta and 14 P. S. Clezy, in The Porphyrins, ed. D. Dolphin, Academic
M. Ravikanth, Coord. Chem. Rev., 2006, 250, 468; Press, New York, 1978, vol. 2, pp. 103–130.
(d) Y. Matano, T. Nakabuchi and H. Imahori, Pure Appl. 15 A. H. Jackson, G. W. Kenner and K. M. Smith, J. Chem. Soc.
Chem., 2010, 82, 583; (e) K. Singh, A. Sharma and
S. Sharma, Adv. Heterocycl. Chem., 2012, 106, 111.
2 T. D. Lash, in The Porphyrin Handbook, ed. K. M. Kadish,
C, 1968, 294. For examples of related systems, see:
(a) T. D. Lash and Y. L. S.-T. Armiger, J. Heterocycl. Chem.,
1991, 28, 965; (b) T. D. Lash, J. Org. Chem., 1992, 57, 4312.
K. M. Smith and R. Guilard, Academic Press, San Diego, 16 (a) A. L. Balch, Coord. Chem. Rev., 2000, 200–202, 349–377;
2000, vol. 2, pp. 125–199.
3 (a) T. D. Lash, Synlett, 2000, 279; (b) T. D. Lash, Eur. J. Org.
Chem., 2007, 5461.
(b) P. R. Ortez De Montellano and K. Auclair, in
The Porphyrin Handbook, ed. K. M. Kadish, K. M. Smith and
R. Guilard, Elsevier, San Diego, 2003, vol. 12, pp. 183–210.
4 T. D. Lash, in Handbook of Porphyrin Science – With Appli- 17 (a) T. D. Lash and S. T. Chaney, Chem.–Eur. J., 1996, 2, 944;
cations to Chemistry, Physics, Material Science, Engineering,
Biology and Medicine, ed. K. M. Kadish, K. M. Smith and
R. Guilard, World Scientific Publishing, Singapore, 2012,
vol. 16, pp. 1–329.
(b) D. Liu and T. D. Lash, Chem. Commun., 2002, 2426;
(c) D. Liu, G. M. Ferrence and T. D. Lash, J. Org. Chem.,
2004, 69, 6079; (d) T. D. Lash and K. M. Bergman, J. Org.
Chem., 2012, 77, 9774.
5 L. Latos-Grazynski, in Handbook of Porphyrin Science – With 18 (a) K. R. Adams, R. Bonnett, P. J. Burke, A. Salgado and
Applications to Chemistry, Physics, Material Science, Engineer-
ing, Biology and Medicine, ed. K. M. Kadish, K. M. Smith
and R. Guilard, World Scientific Publishing, Singapore,
2010, vol. 2, pp. 103–192.
6 (a) T. D. Lash, S. T. Chaney and D. T. Richter, J. Org. Chem.,
1998, 63, 9076; (b) D. T. Richter and T. D. Lash, Tetra-
hedron, 2001, 57, 3659; (c) T. D. Lash, J. T. Szymanski and
M. A. Valles, J. Chem. Soc., Perkin Trans. 1, 1997, 1769;
(b) A. N. Kozyrev, J. L. Alderfer, T. J. Dougherty and
R. K. Pandey, Angew. Chem., Int. Ed., 1999, 38, 126.
19 (a) C. Ryppa, D. Niedzwiedzki, N. L. Morozowich,
R. Srikanth, M. Zeller, H. A. Frank and C. Brückner,
Chem.–Eur. J., 2009, 15, 5749; (b) S. Banerjee, M. Zeller and
C. Brückner, J. Porphyrins Phthalocyanines, 2012, 16, 576.
G. M. Ferrence, J. Org. Chem., 2007, 72, 6481; (d) T. D. Lash 20 (a) H. Eguchi, Y. Ohgo, A. Ikezaki, S. Neya and
and V. R. Yant, Tetrahedron, 2009, 65, 9527.
7 (a) M. Stepien and L. Latos-Grazynski, Chem.–Eur. J., 2001,
7, 5113; (b) M. Stepien and L. Latos-Grazynski, Acc. Chem.
Res., 2005, 38, 88.
M. Nakamura, Chem. Lett., 2008, 768; (b) S. Neya,
M. Suzuki, H. Ode, T. Hoshino, Y. Furutani, H. Kandori,
H. Hori, K. Imai and T. Komatsu, Inorg. Chem., 2008, 47,
10771.
8 K. Berlin and E. Breitmaier, Angew. Chem., Int. Ed. Engl., 21 These results were presented, in part, at the 235th National
1994, 33, 219.
Meeting of the American Chemical Society, New Orleans,
LA, April 2008 (A. M. Young and T. D. Lash, Abstracts of
Papers, ORGN 375).
9 R. Mysliborski, L. Latos-Grazynski and L. Szterenberg,
Eur. J. Org. Chem., 2006, 3064.
10 T. D. Lash, K. Pokharel, J. M. Serling, V. R. Yant and 22 T. D. Lash, Chem.–Eur. J., 1996, 2, 1197.
G. M. Ferrence, Org. Lett., 2007, 9, 2863. See also: E.-K. Sim, 23 T. D. Lash, D. T. Richter and C. M. Shiner, J. Org. Chem.,
S.-D. Jeong, D.-W. Yoon, S.-J. Hong, Y. Kang and C.-H. Lee,
Org. Lett., 2006, 8, 3355.
1999, 64, 7973.
24 T. D. Lash and A. L. Von Ruden, J. Org. Chem., 2008, 73,
11 R. Mysliborski, K. Rachlewicz and L. Latos-Grazynski,
Inorg. Chem., 2006, 45, 7828.
12 (a) F. H. Carré, R. J. P. Corriu, G. Bolin, J. J. E. Moreau and
9417.
25 A. M. Young, A. L. Von Ruden and T. D. Lash, Org. Biomol.
Chem., 2011, 9, 6293.
C. Vernhet, Organometallics, 1993, 12, 2478; (b) S.-D. Jeong, 26 J. L. Sessler, M. R. Johnson and V. Lynch, J. Org. Chem.,
S.-J. Hong, K. J. Park, S. Ham, J. L. Sessler, V. Lynch and 1987, 52, 4394.
C.-H. Lee, J. Org. Chem., 2007, 72, 6232; (c) J. Setsune and 27 T. D. Lash, J. Porphyrins Phthalocyanines, 1997, 1, 29.
K. Watanabe, J. Am. Chem. Soc., 2008, 130, 2404; 28 In the earlier work,8 the carbonyl resonance in the
(d) J.-i. Setsune and K. Watanabe, J. Porphyrins Phthalo-
cyanines, 2012, 16, 508; (e) Z. Zhang, J. M. Lim, M. Ishida,
V. V. Roznyatovskiy, V. M. Lynch, H.-Y. Gong, X. Yang,
carbon-13 NMR spectrum for 6a in CDCl3 was reported to
be present at 167.7 ppm. However, our results consistently
show this peak at values of >180 ppm.
6848 | Org. Biomol. Chem., 2013, 11, 6841–6848
This journal is © The Royal Society of Chemistry 2013