Pyrazinoporphyrins: Expanding a Pyrrolic Building Block in meso-Tetraphenylporphyrin by a Nitrogen Atom

Article abstract of DOI:10.1002/ejoc.201501436

Application of a variant of our "porphyrin breaking and mending strategy" to free base and Ni^II complexes of meso-tetraarylporphyrin-dihydroxylation, oxidative diol cleavage and reaction of the resulting seco-chlorin bis(aldehyde) with ammonia-generates pyrazinoporphyrins. Thus, a nitrogen atom was inserted between the two former β-carbon atoms, overall formally replacing a pyrrolic building block by a pyrazine moiety. Treatment of the initially formed pyrazine hemiaminals with alcohols converts them into the corresponding hemiaminal ethers. This stabilizes the chromophores significantly, but the free-base pyrazinoporphyrins still remain sensitive toward (acid-induced) degradation reactions. Free-base pyrazinoporphyrins possess slightly redshifted porphyrin-type UV/Vis spectra, while the spectra of the pyrazinoporphyrin Ni^II complexes resemble more those of metallochlorins.

Full text of DOI:10.1002/ejoc.201501436

DOI: 10.1002/ejoc.201501436
Full Paper
Pyrazine-Based Porphyrinoids
Pyrazinoporphyrins: Expanding a Pyrrolic Building Block in
meso-Tetraphenylporphyrin by a Nitrogen Atom
Michelle L. Head,[a][‡] Gloria Zarate,[a][‡] and and Christian Brückner*[a]
Abstract: Application of a variant of our “porphyrin breaking with alcohols converts them into the corresponding hemiami-
and mending strategy” to free base and NiII complexes of meso-
tetraarylporphyrin – dihydroxylation, oxidative diol cleavage
and reaction of the resulting seco-chlorin bis(aldehyde) with
ammonia – generates pyrazinoporphyrins. Thus, a nitrogen
atom was inserted between the two former ꢀ-carbon atoms,
overall formally replacing a pyrrolic building block by a pyrazine
moiety. Treatment of the initially formed pyrazine hemiaminals
nal ethers. This stabilizes the chromophores significantly, but
the free-base pyrazinoporphyrins still remain sensitive toward
(acid-induced) degradation reactions. Free-base pyrazinopor-
phyrins possess slightly redshifted porphyrin-type UV/Vis spec-
tra, while the spectra of the pyrazinoporphyrin NiII complexes
resemble more those of metallochlorins.
Introduction
The past two decades have seen an enormous increase in the
synthesis of porphyrin isomers,[1] porphyrin analogues contain-
ing more than four pyrrolic building blocks (the so-called ex-
panded porphyrins),[2] or non-pyrrolic building blocks.[1c,3] Their
study has contributed to the fundamental understanding of the
key concept of aromaticity, the chemical and photophysical
properties of porphyrins and chlorins, and it has provided
chromophores with unprecedented properties, particularly with
respect to long-wavelength absorption, anion recognition, and
metal coordination properties.
Among the porphyrinoids containing non-pyrrolic building
blocks are a number in which a ꢀ-carbon atom of the parent
porphyrin was replaced by a nitrogen atom,[3e] such as imid-
azoloporphyrins 1,[4] 2,[5] and 3.[4b] Two adjacent ꢀ-carbon at-
oms were replaced in triazoloporphyrin 4,[6] and related tria-
zole- and thiadiazole-substituted phthalocyanines.[7] N-Con-
fused porphyrin 5 is an example of a porphyrin isomer but can
also be interpreted as a carbaporphyrin with a ꢀ-nitrogen
atom.[8] Similarly, pyrazoloporphyrins[9] or pyrazole-containing
hexaphyrin analogues[10] are ꢀ,ꢀ′-dinitrogen carbaporphyrin de-
rivatives. In rare cases, a nitrogen atom was inserted between
two ꢀ,ꢀ′-carbon atoms, as shown in imide-functionalized por-
phyrin 6.[11]
Two fundamentally different approaches toward the synthe-
sis of porphyrinoids containing a non-pyrrolic building block
are available:[3e] The total synthesis of the macrocycles, as prac-
ticed for porphyrinoids 2, 4, and 5, or the stepwise conversion
of meso-tetraphenylporphyrin, a pathway used to access por-
phyrinoids 1, 3, and 6.
[a] Department of Chemistry, University of Connecticut
Storrs, CT 06368-3060, U.S.A.
E-mail: c.bruckner@uconn.edu
http://bruckner.research.uconn.edu
[‡] Equal contributions
A key aspect of our ongoing work is the systematic study of
the stepwise formal replacement of a pyrrolic building block in
porphyrins or chlorins by a non-pyrrolic building block.[3e] Im-
ide 6, for example, was prepared by a Beckmann rearrangement
of a porphyrin dione oxime, itself prepared in three steps from
Supporting information and ORCID(s) from the author(s) for this article
are available on the WWW under http://dx.doi.org/10.1002/
ejoc.201501436.
Eur. J. Org. Chem. 2016, 992–998
992
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
the corresponding porphyrin.[11] This “porphyrin breaking and
In a report on the electrochemical reduction of a number of
mending” strategy is further exemplified in Scheme 1, the ring- NiII complexes of porphyrins and porphyrin analogues, such as
expansion of meso-tetraphenylporphyrin 7a by an oxygen 9aNi and 10aNi, we included a pyrazinoporphyrin NiII complex,
atom.[12] An OsO4-mediated dihydroxylation reaction of 7a gen- though we did not report any details of its formation.[15] More-
erates dihydroxychlorin 8a.[12a] This diol is oxidatively cleaved, over, at that time, only the particularly stable NiII complex 9aNi
forming seco-chlorin bis(aldehyde) 9a.[13] Treatment with alco- was known, and the free-base seco-chlorin bis(aldehyde) 9a had
hol under acid catalysis led to a ring-closure reaction and sub- not yet become available. This has changed,[13c] and free-base
sequent double-acetal formation, generating morpholinochlor- seco-chlorin bis(aldehyde) 9a demonstrated its versatility in the
ins 10a/10aNi.[12] Other nucleophiles eliciting this morpholine- formation of a number of porphyrinoids containing non-pyr-
forming ring-closure reaction are known.[12d] The final products rolic heterocycles.[12b,13c,16] This prompted us to investigate its
are chlorin analogues possessing redshifted optical spectra.[12] reaction with ammonia with the goal of preparing the free-base
Not all nucleophiles provide the expected products, however. pyrazino derivatives. Free-base chromophores are frequently
For instance, the reaction of seco-chlorin bis(aldehyde) with fluorescent, potentially photosensitizers for singlet oxygen, and
hydrazine did not lead to the expected triazepin derivative. In- they allow the preparation of a wide variety of metal com-
stead, a porphyrin was formed by an N2-extrusion reaction.[14]
plexes.[17] The nickel complexes are often chemically very sta-
ble, but nonfluorescent, possess no photosensitization abilities,
and the removal of the NiII atom from the complexes requires
harsh conditions,[17] if it can be accomplished at all without the
destruction of the chromophore.[12a] The investigation of the
pyrazine-based porphyrinoids is hoped to further unravel the
correlation between non-pyrrolic moiety, conformation, confor-
mational flexibility, and optical properties.[11,12,18] Furthermore,
the pyrazine nitrogen atom that is part of the chromophore can
be potentially utilized for sensing applications, as shown for
other pyrrole-modified porphyrins with functionalities at their
chromophore.[19] This report presents our findings on the for-
mation and properties of the free base and NiII complexes of
pyrazinoporphyrins.
Results and Discussion
Reaction of Secochlorin 9aNi with Ammonia
Reaction of brown-yellow seco-chlorin 9aNi[12a] with aqueous
ammonia in THF in homogeneous solution generates immedi-
ately a bright green, very polar compound, 11aNi (Rf < 0.1,
alumina/CH2Cl2) (Scheme 2). The ESI+ HR-MS data of the parent
Scheme 1. Ring expansion of tetraphenylporphyrin by an oxygen atom.
Scheme 2. Formation of pyrazinoporphyrins.
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
993
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Scheme 3. Mechanism of formation of the pyrazinoporphyrins.
ion ([11aNi·H]+) suggested that, relative to the composition of 171.8 ppm) is also very prominent in the 13C NMR spectrum of
the starting material, an uptake of a nitrogen atom with con- 12aNi.
comitant loss of 1 equiv. of water had taken place. Prominent
in the mass spectrum of 11aNi was also a fragment ion peak
corresponding to the loss of another equivalent of water
([11aNi – H2O]+), suggesting the facile loss of a hydroxy group.
This, in turn, is indicative of the presence of a moiety that
greatly stabilizes a (carbo)cation.
The UV/Vis spectra of 11aNi and 12aNi are identical to each
other, and typical in overall shape and Q-band position (λmax
=
621 nm) for an NiII chlorin, as illustrated by comparison of the
spectrum for the diol chlorin NiII complex 8aNi (Figure 1). In
contrast, NiII porphyrin 7aNi possesses a λmax band at 525 nm.
However, the Soret band of pyrazinoporphyrin complex 12aNi
Treatment of crude 11aNi with MeOH and catalytic quanti- is bathochromically shifted by 22 nm relative to that of diol
ties of acid generated compound 12aNi of much reduced – chlorin nickel 8aNi. In comparison, the UV/Vis spectrum of the
albeit still significant – polarity (Rf = 0.40, alumina/CH2Cl2; Rf = NiII complex of imide 6 containing two sp2-hybridized ring
0.28, silica/2.5 vol.-% MeOH in CH2Cl2). The ESI+ HR-MS data of atoms in the non-pyrrolic moiety is redshifted as that of an
12aNi confirmed the replacement of a proton by a methyl NiII porphyrin (λSoret = 439 nm, λmax = 626 nm),[11] whereas
group. The major fragmentation was the loss of MeOH, result- morpholinochlorin 10aNi containing two sp3-hybridized ring
ing in the formation of the identical cationic species resulting atoms also possesses an NiII chlorin spectrum (λSoret = 430 nm,
from the loss of water from 11aNi. These data support the for- λmax = 640 nm).[12a]
mation of the pyrazinoporphyrin structures 11aNi and its me-
thoxy derivative 12aNi.
Based on precedent reactions of seco-chlorin bis(aldehydes)
with nucleophiles (Scheme 2),[12] the mechanism of the reaction
can be deduced in a straightforward manner (Scheme 3): Nu-
cleophilic attack of the amine on one aldehyde group of 9a
forms hemiacetal I. Two potential nucleophiles are now avail-
able for an intramolecular ring-closure reaction: the alcohol
functionality to form a morpholinochlorin or the amine func-
tionality to form a pyrazino derivative. Evidently, the higher nu-
cleophilicity of the amine wins, and the pyrazine intermediate
II is formed. Loss of water forms the α-hydroxy imine function-
ality in 11a with the double bond in conjugation with the por-
phyrinic chromophore. Note that elimination of 1 equiv. of wa-
Figure 1. UV/Vis spectra (CH2Cl2) of the nickel complexes indicated.
ter is not possible had a morpholinochlorin been formed. The
hemiacetal moiety is readily converted into a hemiacetal ether
12a as well as a stable carbocation under ESI+ MS conditions
Reaction of Free-Base seco-Chlorin 9a with Ammonia
(Scheme 2).
The NMR spectroscopic data of the pyrazinochlorin 12aNi
(and the free bases 11a/12a described below) suggest that
they are formed as racemic mixtures. For a detailed discussion
of the NMR spectra and the stereostructures of the pyrazinopor-
phyrins, see below.
The formation of the free-base pyrazinoporphyrin proceeded in
a fashion similar to that described for the NiII complex. How-
ever, free-base seco-chlorins 9a and 9b were, because of their
chemical lability, freshly prepared and immediately used as
crude material.[13c] When the seco-chlorins were treated under
The NMR spectra of 12aNi also support the methoxy-substi- aerobic conditions with a stoichiometric excess of aq. concd.
tuted pyrazinoporphyrin connectivity. The 1H NMR spectrum ammonia in pyridine at slightly elevated temperatures (ca. 40–
shows a molecule lacking symmetry; six signals for ꢀ-protons 50 °C), the rapid formation of a polar (Rf = 0.5, silica/2.5 vol.-
can be made out, for example. Three singlets stand out: one at % THF in CHCl3) burgundy-brown product was observed. The
the high-field edge, at δ = 9.12 ppm (1 H), assigned to the reaction was completed, as monitored by TLC, after 20 min,
imine proton, one at the high-field edge of the aromatic CH and the products were isolated by preparative plate or column
protons, at δ = 6.78 ppm (1 H), assigned to the hydrogen atom chromatography. The products showed the expected composi-
on the ring sp3-carbon atom, and a signal at δ = 2.86 ppm tions, as per ESI+ HR-MS, and the diagnostic NMR signatures
(3 H) for the methoxy group. The imine carbon signal (δ = (nonsymmetric molecule; appearance of a diagnostic imine
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
994
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
hydrogen signal at δ = 9.25 ppm; inner NH signals at δ = pyrazinoporphyrins. Their extinction coefficients are signifi-
–1.6 ppm) expected for pyrazinoporphyrin hemiacetals 11a or cantly smaller than those of porphyrin 7a, likely a reflection of
11b, respectively. While the NiII complex 12aNi was stable even their presumed slight nonplanarity. Pyrazinoporphyrin imide 6
under acidic conditions, we noted that the free-base analogues also possessed a porphyrin-like optical spectrum.[11] This is in
were very sensitive to decomposition, particularly under acidic contrast to, for example, the chlorin-like spectra of the morphol-
or oxidative conditions (see also below).
inochlorins,[12b] such as 10a. This dichotomy seen in the UV/Vis
spectra within a compound class – the free base is porphyrin-
like, and the metal complex is metallochlorin-like – was noted
before for the optical properties of the porpholactones, porphy-
rinoids in which a porphyrin ꢀ,ꢀ′-bond was replaced by a lact-
one moiety.[16c] Reflecting the negligible influence of the alkyl
substituents on the meso-phenyl group, the UV/Vis spectra of
all free-base pyrazinoporphyrins 12a and 12b are nearly identi-
cal (see Supporting Information). Their two-band fluorescence
spectra (λemission = 670 and 750 nm, in a 1:0.44 intensity ratio)
are also porphyrin-like (see Supporting Information).
Nonetheless, conversion of hemiacetals 11a and 11b into
the brown (color on TLC) hemiacetal ethers 12a and 12b, re-
spectively, by using EtOH under neutral conditions or acid catal-
ysis (traces of TFA fumes applied by pipette) was possible. These
alkylated compounds are more readily isolated and handled
than the hydroxylated species primarily because of their relative
higher chemical stabilities, but also because of their lower po-
larities (Rf = 0.51, silica/2 vol.-% THF in CHCl3). We found it none-
theless necessary to neutralize the acidity of the preparative
silica gel TLC plates used to purify the free-base chromophores
in a chamber over Et3N for up to 1 week to significantly reduce
All other attempts to modify pyrazinoporphyrins 11a/b and
the decomposition of the pyrazinoporphyrins 12a/b during 12a/b failed (such as reduction reactions, oxidations, acid-in-
chromatography.
duced intramolecular ring fusions[12c,12d]) because of their pro-
nounced chemical lability.[21] For instance, protonation of the
pyrazinoporphyrins in a UV/Vis cell with traces of TFA generates
spectra with a broad λmax band at ca. 940 nm, but this protona-
tion is not reversible. Even immediate neutralization of the acid-
ified solution with NH4OH or Et3N does not recover the pyrazi-
noporphyrin spectra (see Supporting Information). Performance
of this acid-induced reaction at a preparative scale allowed the
isolation of two major chromophores that could, however, not
be characterized. MS suggested the uptake of one and two
oxygen atoms, and their UV/Vis spectra were typical for ring-
opened, biline-type chromophores, an interpretation also sup-
ported by the presence of D2O-exchangeable protons at the
The out-of-porphyrin-plane configuration of the ethoxy
group on the sp3-hybridized carbon atom is indicated by the
diastereotopic splitting of the two methylene signals.[12a–12c] All
other spectroscopic findings for the hemiacetal ethers 12a/b
are analogous to their corresponding hemiacetals 11a/b.
The UV/Vis spectra of free-base pyrazinoporphyrins 11a and
12a are essentially identical (Figure 2; see Supporting Informa-
tion for a direct comparison of the spectra of 11a and 12a).
Compared to the spectrum of the parent porphyrin 7a (λSoret
419 nm, λmax = 648 nm), they feature a broadened and red-
shifted Soret band (at 431 nm), with redshifted Q-bands (λmax
668 nm). The descending intensity of their Q-bands with in-
creasing wavelengths characterizes them as porphyrin-like
chromophores.[20] We therefore named these porphyrinoids
=
=
1
low-field edge of their H NMR spectra (data presented in the
Supporting Information).
Stereochemical Considerations
The NMR spectra of the free-base and nickel(II) pyrazinopor-
phyrins 12a, 12b, and 12aNi indicate the presence of only a
single compound. The sp3-hybridized pyrazine carbon atom is
chiral, hence we expect all compounds to be present as racemic
mixtures. However, our work on the stereostructure of the re-
lated morpholinochlorins suggests that the situation is likely
more complex:[12c,12d,22] It is well known that the small ion
nickel(II) induces a ruffled conformation in porphyrins.[13b] This
ruffling introduces a chiral helimeric axis into the molecule [en-
antiomers designated (M) and (P); idealized point group C2]
(Figure 3A). The ruffling is particularly pronounced in the seco-
chlorin nickel complexes, such as 9aNi and is largely preserved
in the resulting nickel morpholinochlorins, such as 10aNi,[13b]
but is also still present in the free-base morpholinochlorins,
such as 10a.[12d] Nonetheless, the presence of two chiral sp3-
carbon atoms in morpholinochlorins in combination with a chi-
ral axis did not result in the formation of a number of diastereo-
mers. Instead, the ruffling distortion orients the meso-phenyl
groups adjacent to the morpholine moiety in such a way that
sterically one of the two possible isomers [(R) or (S)] of the
flanking sp3-carbon atoms is fully blocked. Thus, the stereo-
Figure 2. UV/Vis spectra (CH2Cl2) of the free-base chromophores indicated.
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
995
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
structure of the three chiral elements are tightly coupled, and tion that the conformation of the chromophores are not drasti-
only a racemic pair is observed.[12d] We suspect a similar process cally altered as a result of the modification, but a slight ruffling,
to take place in the pyrazinoporphyrins, though we lack direct particularly for the nickel complexes, can be safely assumed.
(structural) evidence for this hypothesis. The nickel(II) complex While the NiII complex is reasonably stable, the further investi-
12b can reasonably be expected to be ruffled, thus exercising gation and potential utility of the free-base chromophores are
the same shielding on the flanking sp3 center. This would in- much hampered by their relatively high chemical instability,
duce the formation of only one stereoisomer at this carbon particularly in acidic environments.
atom, thus giving rise to the formation of only one racemic pair
[such as (M-R) and (P-S), but (M-S), for example, would not be
formed] (Figure 3B and C).
Experimental Section
Materials and Instrumentation: All solvents and reagents used
were reagent grade or better and were used as received. Dihydroxy-
chlorins 4aH2, 4aNi, and 4bH2,[16c,23] and seco-chlorin bis(alde-
and 5aNi[12a] were prepared as described in the
[13c]
hydes) 5aH2
literature. The analytical TLC plates used were Silicycle ultra pure
silica gel 60 (aluminum backed, 250 μm), and the preparative chro-
matography plates (500 μm or 1.0 mm silica gel on glass) used were
both provided by Scientific Adsorbents Inc., Atlanta, GA. The prepar-
ative chromatography plates were stored in a chamber over a bowl
of Et3N for up to 1 week prior to use. 1H and 13C NMR spectra were
recorded with Bruker 300 and 400 MHz instruments in the solvents
indicated and are referenced to residual solvent peaks. UV/Vis spec-
tra were recorded with a Cary 50 spectrophotometer, fluorescence
spectra with a Cary Eclipse fluorimeter, both Varian, Inc. High- and
low-resolution mass spectra were provided by the Mass Spectro-
metry Facility, Department of Chemistry, University of Connecticut.
Figure 3. (A) Pictorial representation of the (M) and (P) helimeric enantiomers
of ruffled nickel porphyrinoids, as known for morpholinochlorin nickel com-
plex 10aNi, and assumed for 12aNi. (B) Expression of only one of the two
possible diasteromers of a given macrocycle helicity if the macrocycle confor-
mation induces the formation of only one of the two possible stereoisomers.
(C) Two enantiomers assumed to be present in 11aNi, 12aNi. (D) Two enanti-
omers possible for planar pyrazinoporphyrins, as is possible for the free-base
chromophores.
[meso-Tetraphenylhydroxypyrazinoporphyrinato]NiII (11aNi): In
a 50 mL round-bottom flask equipped with a stir bar, seco-por-
phyrin bis(aldehyde) 9aNi (150 mg, 0.21 mmol) was dissolved in
THF (25 mL), and concd. NH4OH (0.25 mL) was added. The reaction
mixture was stirred for 20 min. When TLC had indicated the com-
plete consumption of the starting material, the reaction mixture
was filtered through a short plug of neutral alumina, and the sol-
vents were evaporated to dryness by rotary evaporation. The resi-
There are two scenarios for the free-base pyrazinoporphyr-
ins: one in which the macrocycle is also ruffled, mirroring the
situation of the nickel complex (and of free-base morpholino-
chlorins),[12d] and one in which the chromophore is planar. As
a result of this planarity, the meso-phenyl groups are in plane
and do not exercise any preference on the sp3 center. Thus, the
racemic mixture arises solely from the two possibilities at sp3
center (Figure 3D).
1
due was mainly composed of 11aNi. Rf < 0.1 (alumina/CH2Cl2). H
NMR (400 MHz, [D6]DMSO, 25 °C): δ = 9.05 (s, 1 H, CH=Npyrazine),
3
3
8.40 (br. d, JH,H = 7 Hz, 1 H, o-Ph-H), 8.38 (d, JH,H = 4.8 Hz, 1 H, ꢀ-
3
H), 8.27–8.35 (m, 3 H, ꢀ-H), 8.04 (d, JH,H = 4.8 Hz, 1 H, ꢀ-H), 7.90–
7.75 (br. m, 4 H, o-Ph-H), 7.70 (t, JH,H = 7 Hz, 1 H, m/p-Ph-H), 7.65–
7.50 (m, 12 H, Ph-H), 7.35 (t, JH,H = 7 Hz, 2 H, m/p-Ph-H), 6.88 (br.
3
3
d, 1 H, Npyrazine-CH) ppm. UV/Vis (CH2Cl2): λmax (rel. intensity) = 436
(1.0), 520 (sh), 570 (0.06), 621 (0.15) nm. MS (ESI+, 100 % CH3CN,
cone voltage = 30 V): m/z (%) = 701.9 (80) [M·H]+, 684.1 (100)
[M – H2O]+. HR-MS (ESI+, 100 % CH3CN, cone voltage = 30 V, TOF):
calcd. for C44H30N5NiO [M·H]+ 702.1798; found 702.1792.
Conclusions
The “porphyrin breaking and mending strategy” can be used to
expand a pyrrole in meso-tetraarylporphyrins by a nitrogen
atom to produce a pyrazinoporphyrin. This is only the second
example, after imide 6,[11] in which a pyrrole of a porphyrin was
[meso-Tetraphenylmethoxypyrazinoporphyrinato]NiII (12aNi):
The entire batch of crude 11aNi prepared as described above was
dissolved in CHCl3 (20 mL), MeOH (0.5 mL), and a drop of concd.
aq. HCl was added. The reaction mixture was stirred for 10 min,
formally replaced by a pyrazine moiety. An independent strat- transferred to a separatory funnel, washed with satd. aq. NaHCO3
and water, the organic phase was isolated, dried with Na2CO3, and
chromatographed (silica/2.5 vol.-% MeOH in CH2Cl2) to provide
85 mg (56 mol-% yield over two steps from 9aNi) of 12aNi as a
green solid. Rf = 0.40 (alumina/CH2Cl2); Rf = 0.28 (silica/2.5 vol.-%
egy to accomplish this insertion was demonstrated here, gener-
ating a pyrazinoporphyrin with the pyrazine moiety in a lower
oxidation state. Nonetheless, because of the presence of one
sp2-hybridized ꢀ-carbon atom in the pyrazine moiety, the
chromophore of the free-base pyrazinoporphyrins possesses
typical, albeit ca. 20 nm red-shifted, porphyrin-type optical
spectra. In contrast, the NiII complexes exhibit metallochlorin-
type optical properties. This porphyrin/chlorin dualism was pre-
viously also observed for the spectra of the porpholactones.[16c]
1
MeOH in CH2Cl2). H NMR (400 MHz, CDCl3, 25 °C): δ = 9.15 (s, 1 H,
3
3
CH=Npyrazine), 8.45 (d, JH,H = 7.2 Hz, 1 H, o-Ph-H), 8.42 (d, JH,H
=
3
4.8 Hz, 1 H, ꢀ-H), 8.34–8.34 (m, 2 H, ꢀ-H), 8.35 (d, JH,H = 4.8 Hz, 1
H, ꢀ-H), 8.04 (d, JH,H = 4.8 Hz, 1 H, ꢀ-H), 7.97 (d, JH,H = 4.8 Hz, 1
3
3
3
H, ꢀ-H), 7.9 (br. s, 4 H, o-Ph-H), 7.74 (t, JH,H = 7.2 Hz, 1 H, m/p-Ph-
H), 7.63–7.56 (m, 12 H, Ph-H), 7.34 (t, 3JH,H = 7.2 Hz, 1 H, m/p-Ph-H),
3
The otherwise essentially regular UV/Vis spectra are an indica- 6.96 (d, JH,H = 7.2 Hz, 1 H, m/p-Ph-H), 6.66 (s, 1 H, Npyrazine-CH),
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
996
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2.86 (s, 3 H, OCH3) ppm. 13C NMR (100 MHz, CDCl3, 25 °C): δ =
Diol 8b (20 mg, 2.3 × 10–5 mol) was dissolved in CHCl3 (5 mL) at
171.5, 146.4, 143.7, 143.1, 142.1, 139.9, 139.8, 139.6, 137.9, 137.6, room temp. and stirred; Et3N (50 μL) and NaIO4/silica gel (1.0 g)
135.5, 134.0, 133.9, 133.85, 133.5, 133.4, 133.2, 131.6, 131.4, 131.3,
130.8, 128.6, 128.4, 128.35, 128.3, 128.2, 127.9, 127.7, 127.6, 124.5,
were added. As the solution changed color from burgundy to
brownish-yellow within 20 min, TLC control assured the complete
123.6, 116.0, 114.8, 86.8, 55.9 ppm. UV/Vis (CH2Cl2): λmax (log ε) = consumption of the diol; more NaIO4/silica was added as needed.
436 (5.22), 520 (sh), 570 (4.55), 621 (4.25) nm. MS (ESI+, 100 % After less than 15 min, the reaction had reached completion. The
CH3CN, cone voltage = 30 V): m/z (%) = 715 (20) [M]+, 684 (100) [M
– H2O]+. HR-MS (ESI+, 100 % CH3CN, cone voltage = 30 V, TOF):
calcd. for C45H31N5NiO [M+] 715.1882; found 715.2001.
formation of the seco-chlorin aldehyde is indicated by its diagnostic
UV/Vis spectrum;[13c] Rf = 0.07 (silica/2.5 vol.-% THF in CHCl3). The
mixture was filtered by using a glass frit (M) and the filtrate dried
by rotary evaporation. The resulting brown-yellow film of 9c (ca.
20 mg, 2.30 × 10–5 mol) was dissolved in freshly distilled pyridine
(ca. 20 mL), the solution was warmed to 40–50 °C, and concd.
NH4OH (2 mL) was added. As the brownish-yellowish solution
changed its color to brown-burgundy and was heated to reflux for
30 min, the reaction progress was monitored by TLC and UV/Vis
spectroscopy. Upon completion of the reaction, as per TLC, the solu-
tion was dried by rotary evaporation, and the crude material was
passed through a short column (silica/2.5 vol.-% THF in CHCl3; the
solvent was deacidified prior to use by passing it through a column
of basic alumina). Crude 11b: Rf = 0.5 (silica/2.5 vol.-% THF in CHCl3).
1H NMR (300 MHz, CDCl3, 25 °C): δ = 9.23 (s, 1 H, CH=Npyrazine), 8.74
meso-Tetraphenylhydroxypyrazinoporphyrin (11a): Freshly pre-
pared meso-tetraphenyl-seco-chlorin bis(aldehyde) 9a[13c] (50 mg,
7.7 × 10–5 mol) was dissolved in THF (ca. 5 mL), followed by concd.
NH4OH (3 mL) and stirred at ambient temperature. The reaction
mixture was monitored by TLC. Once the nonpolar, brown spot of
seco-chlorin 9a was consumed [Rf = 0.89 (silica/2.5 vol.-% THF in
CH2Cl2)], the reaction mixture was filtered through a glass frit (M),
the filtrate was transferred to a separatory funnel, CH2Cl2 (ca. 20 mL)
was added, and the solution was washed with distilled water (3 ×).
The concentrated organic phase was purified by preparative plate
chromatography to provide 11a in ca. 90 % yield as a film. Rf = 0.14
(silica/2.5 vol.-% THF in CH2Cl2). UV/Vis (CH2Cl2): λmax (rel. inten-
sity) = 429 (1), 532 (0.17), 568 (0.058), 611 (0.038), 667 (0.003) nm.
1H NMR (400 MHz, [D7]DMF, 25 °C): δ = 9.13 (s, 1 H, CH=Npyrazine),
3
3
(d, JH,H = 5 Hz, 1 H, ꢀ-H) overlapping with 8.70 (d, JH,H = 5 Hz, 1
H, ꢀ-H), 8.65–8.55 (m, 2 H, ꢀ-H), 8.53–8.30 (m, 4 H, ꢀ-H), 7.9–7.7 (m,
3
8 H, o,m-Ph-H), 7.62 (d, JH,H = 8 Hz, 2 H, o,m-Ph-H), 7.58–7.40 (m,
3
3
8.80 (d, JH,H = 5.2 Hz, 1 H, ꢀ-H), 8.77 (d, JH,H = 5.2 Hz, 1 H, ꢀ-H)
8.45–8.65 (m, 6 H, 2 o-Ph-H + 4 ꢀ-H), 7.75–8.0 (m, 12 H, Ph-H), 7.7
6 H, o,m-Ph-H), 7.3 (br. s, 1 H, Npyrazine-CH), 2.5 (m, 4 H, CHMe2), 1.1
(m, CH3, 12 H), –1.6 (br. s, 2 H, NH) ppm. HR-MS (ESI+, 100 % CH3CN,
cone voltage = 70 V): m/z = 870 [MH+], 852 [M – H2O]+. 1H NMR:
see Supporting Information. Crude product 11b was immediately
dissolved in EtOH (ca. 20 mL), shielded from light with aluminum
foil, and stirred at ambient temperature. The color of the solution
remained brown as a low-polarity product formed. Upon comple-
tion as per TLC (after up to 2 h), the solution was concentrated to
dryness by rotary evaporation and the residue purified by prepara-
tive plate chromatography (silica/1.25 vol.-% THF in CHCl3) to pro-
vide 12b as a purple-brown solid (12 mg, 58 % from diol 8c). Rf =
0.51 (silica/2.5 vol.-% THF in CHCl3). UV/Vis (CH2Cl2): λmax (log ε) =
432 (4.87), 538 (3.74), 573 (3.60), 613 (3.41) 668 (3.12) nm. Fluores-
cence (CH2Cl2, λexcitation = 433 nm): λmax = 675 nm. 1H NMR
(300 MHz, CDCl3, 25 °C): δ = 9.2 (s, 1 H, CH=Npyrazine), 8.74 (br. s, 1
H, ꢀ-H), 8.68 (br. s, 1 H, ꢀ-H), 8.62–8.55 (m, 2 H, ꢀ-H), 8.5–8.4 (m, 4
H, ꢀ-H, o,m-Ph-H), 8.2–8.0 (br. s, 2 H, o-Ph-H), 7.9–7.8 (m, 2 H, o,m-
Ph-H), 7.8–7.7 (m, 5 H, o,m-Ph-H), 7.7–7.6 (m, 1 H, o,m-Ph-H), 7.6–
7.5 (m, 2 H, o,m-Ph-H), 7.5–7.4 (m, 2 H, o,m-Ph-H), 7.04 (s, 1 H,
3
(m, 2 H, Ph-H), 7.55 (br. s, 2 H, Ph-H), 7.23 (d, JH,H = 4.0 Hz, 1 H,
Npyrazine-CH), 6.19 (d, JH,H = 4.0 Hz, 1 H, OH, exchangeable with
3
D2O), –1.6 (br. s, 2 H, NH, exchangeable with D2O) ppm. 13C NMR
(100 MHz, [D7]DMF, 25 °C): δ = 167.9, 154.6, 153.3, 152.2, 142.4,
141.4, 141.3, 141.2, 140.4, 139.5, 138.0, 136.9, 136.8, 136.0, 134.3,
134.1, 134.0, 133.4, 132.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2,
127.8, 127.7, 127.6, 127.5, 127.4, 125.4, 123.4, 121.5, 119.4, 119.0,
67.5 ppm. MS (ESI+, 100 % CH3CN, cone voltage = 5 V): m/z (%) =
647 (65) [M·H]+, 628 (100) [M – H2O]+. HR-MS (ESI+, 100 % CH3CN,
cone voltage = 30 V, TOF): calcd. for C44H32N5O+ [M·H]+ 646.2601;
found 646.2890.
meso-Tetraphenylethoxypyrazinoporphyrin (12a): Prepared in
up to 75 % yield (15 mg) from 8a (20 mg, 3.0 × 10–5 mol) according
to the procedure described for 12b or from crude 11a in THF
(20 mL) and EtOH (1 mL). Fumes of TFA, taken from the headspace
of a bottle, were puffed into the flask to catalyze the final step,
whereby too much acid reduced the yield on expense of the forma-
tion of an unknown green product (see Supporting Information).
Purified by preparatory plate TLC (silica/2.5 vol.-% THF in CH2Cl2).
Rf = 0.40 (silica/3.3 vol.-% THF in CH2Cl2). UV/Vis (CH2Cl2): λmax (ε) =
3
3
Npyrazine-CH), 3.78 (dq, JH,H = 7.2, 9.4 Hz, 1 H), 3.27 (dq, JH,H = 7.2,
9.4 Hz, 1 H), 2.62 (m, 4 H, CHMe2), 1.2 (m, 12 H, CH3), 0.93 (m, 6 H),
–1.55 (br. s, 2 H, exchangeable with D2O, NH) ppm. 13C NMR
(125 MHz, CDCl3, 25 °C): δ = 169.8, 155.0, 153.5, 151.4, 151.0, 150.9,
150.9, 150.8, 148.6, 140.5, 139.4, 138.7, 138.5, 137.4, 138.1, 137.3,
137.3, 137.2, 136.4, 134.4, 134.3, 134.1, 134.1, 133.4, 132.6, 128.4,
128.2, 126.7, 127.6, 124.5, 124.2, 124.1, 124.1, 124.0, 123.5, 121.3,
120.0, 118.6, 83.4, 63.5, 46.2, 35.1, 31.9, 15.6 ppm. IR (neat, ATR): see
Supporting Information. HR-MS (ESI+, 100 % CH3CN, cone voltage =
30 V, TOF): calcd. for C62H68N5O [M·H]+ 898.5424; found 898.5453.
1
429 (4.84), 532 (3.70), 568 (3.55), 611 (3.39), 667 (3.11) nm. H NMR
(400 MHz, [D6]DMSO, 25 °C): δ = 8.96 (s, 1 H, CH=Npyrazine), 8.70 (d,
3
3JH,H = 4 Hz, 1 H, ꢀ-H), 8.66 (d, JH,H = 4 Hz, 1 H, ꢀ-H), 8.5–8.3 (m, 7
3
H, ꢀ-H and o-Ph-H), 7.9–7.6 (m, 18 H), 7.46 (br. d, JH,H = 4 Hz, 1 H,
o,m-Ph-H), 6.8 (s, 1 H, Npyrazine-CH), 3.54 (m, 1 H, OCHAHBCH3) 3.06
3
(m, 1 H, OCHAHBCH3), 0.75 (t, JH,H = 8 Hz, 3 H, OCH2CH3), –1.7 (s, 2
H, NH) ppm. 13C NMR (100 MHz, [D6]DMSO, 25 °C): δ = 168.9, 154.4,
153.1, 151.9, 148.8, 141.8, 140.9, 140.7, 140.7, 139.8, 139.7, 137.5,
137.1, 136.7, 136.6, 136.1, 134.4, 134.3, 133.8, 132.7, 129.1, 129.0,
128.74, 128.65, 128.5, 128.1, 128.0, 127.69, 127.65, 125.4, 123.5,
121.6, 119.4, 118.8, 83.1, 63.3 ppm. MS (ESI+, 100 % CH3CN, cone
voltage = 30 V): m/z = 674 [M·H]+, 628 [M – EtOH]+. HR-MS (ESI+,
100 % CH3CN, cone voltage = 30 V, TOF): calcd. for C46H36N5O
[M·H]+ 674.2914; found 674.2908.
Acknowledgments
This work was supported by the National Science Foundation
(NSF) (grants CHE-0517782 and CHE-1465133).
meso-Tetrakis(4-tert-butylphenyl)ethoxypyrazinoporphyrin
(12b) (from Dihydroxychlorins without Isolation/Purification of
the Intermediate seco-Chlorin or Hydroxypyrazinoporphyrin):
Keywords: Porphyrins · Porphyrinoids · Pyrazines · Ring-
expansion · UV/Vis spectroscopy
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
997
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[1]
[2]
[12] a) C. Brückner, S. J. Rettig, D. Dolphin, J. Org. Chem. 1998, 63, 2094–2098;
b) J. R. McCarthy, H. A. Jenkins, C. Brückner, Org. Lett. 2003, 5, 19–22; c)
H. W. Daniell, C. Brückner, Angew. Chem. Int. Ed. 2004, 43, 1688–1691;
Angew. Chem. 2004, 116, 1720; d) C. Brückner, D. C. G. Götz, S. P. Fox, C.
Ryppa, J. R. McCarthy, T. Bruhn, J. Akhigbe, S. Banerjee, P. Daddario, H. W.
Daniell, M. Zeller, R. W. Boyle, G. Bringmann, J. Am. Chem. Soc. 2011, 133,
8740–8752.
[13] a) C. Brückner, E. D. Sternberg, J. K. MacAlpine, S. J. Rettig, D. Dolphin, J.
Am. Chem. Soc. 1999, 121, 2609–2610; b) C. Brückner, M. A. Hyland, E. D.
Sternberg, J. MacAlpine, S. J. Rettig, B. O. Patrick, D. Dolphin, Inorg. Chim.
Acta 2005, 358, 2943–2953; c) J. Akhigbe, C. Ryppa, M. Zeller, C. Brückner,
J. Org. Chem. 2009, 74, 4927–4933.
[14] J. Akhigbe, L. Samankumara, C. Brückner, Tetrahedron Lett. 2012, 53,
3524–3526.
[15] C. J. Campbell, J. F. Rusling, C. Brückner, J. Am. Chem. Soc. 2000, 122,
6679–6685.
[16] a) J. R. McCarthy, M. A. Hyland, C. Brückner, Org. Biomol. Chem. 2004, 2,
1484–1491; b) K. K. Lara, C. K. Rinaldo, C. Brückner, Tetrahedron 2005, 61,
2529–2539; c) C. Brückner, J. Ogikubo, J. R. McCarthy, J. Akhigbe, M. A.
Hyland, P. Daddario, J. L. Worlinsky, M. Zeller, J. T. Engle, C. J. Ziegler, M. J.
Ranaghan, M. N. Sandberg, R. R. Birge, J. Org. Chem. 2012, 77, 6480–
6494.
[17] J. W. Buchler in Synthesis and Properties of Metalloporphyrins, vol. 1 (Ed.:
D. Dolphin), Academic Press, New York, 1978, pp. 389–483.
[18] a) D. C. G. Götz, A. C. Gehrold, S. J. Dorazio, P. Daddario, L. Samankumara,
G. Bringmann, C. Brückner, T. Bruhn, Eur. J. Org. Chem. 2015, 3913–3922;
b) E. Meehan, R. Li, M. Zeller, C. Brückner, Org. Lett. 2015, 17, 2210–2213;
c) L. P. Samankumara, S. J. Dorazio, J. Akhigbe, R. Li, A. Nimthong-Roldán,
M. Zeller, C. Brückner, Chem. Eur. J. 2015, 21, 11118–11128.
[19] a) Y. Xie, T. Morimoto, H. Furuta, Angew. Chem. Int. Ed. 2006, 45, 6907–
6910; Angew. Chem. 2006, 118, 7061; b) G. E. Khalil, P. Daddario, K. S. F.
Lau, S. Imtiaz, M. King, M. Gouterman, A. Sidelev, N. Puran, M. Ghande-
hari, C. Brückner, Analyst 2010, 135, 2125–2131; c) J. L. Worlinsky, G.
Zarate, M. Zeller, M. Ghandehari, G. Khalil, C. Brückner, J. Porphyrins
Phthalocyanines 2013, 17, 836–849; d) J. L. Worlinsky, S. Halepas, C.
Brückner, Org. Biomol. Chem. 2014, 12, 3991–4001; e) J. L. Worlinsky, S.
Halepas, M. Ghandehari, G. Khalil, C. Brückner, Analyst 2015, 140, 190–
196.
a) Y.-D. Wu, K. W. K. Chan, C.-P. Yip, E. Vogel, D. A. Plattner, K. N. Houk, J.
Org. Chem. 1997, 62, 9240–9250; b) J. L. Sessler, A. Gebauer, E. Vogel in
Porphyrin Isomers, vol. 2 (“Heteroporphyrins, Expanded Porphyrins and
Related Macrocycles”) (Eds.: K. M. Kadish, K. M. Smith, R. Guilard), Aca-
demic Press, San Diego, 2000, pp. 1–54; c) T. D. Lash, J. Porphyrins Phthalo-
cyanines 2012, 15, 423–433.
a) J. L. Sessler, A. Gebauer, S. J. Weghorn in Expanded Porphyrins, vol. 2
(Eds.: K. M. Kadish, K. M. Smith, R. Guilard), Academic Press, San Diego,
2000, pp. 55–124; b) J. L. Sessler, J. M. Davis, Acc. Chem. Res. 2001, 34,
989–997; c) J. L. Sessler, A. E. Vivian, D. Seidel, A. K. Burrell, M. Hoehner,
T. D. Mody, A. Gebauer, S. J. Weghorn, V. Lynch, Coord. Chem. Rev. 2001,
216–217, 411–434; d) T. K. Chandrashekar, S. Venkatraman, Acc. Chem.
Res. 2003, 36, 676–691; e) J. L. Sessler, E. Tomat, Acc. Chem. Res. 2007,
40, 371–379; f) R. Misra, T. K. Chandrashekar, Acc. Chem. Res. 2008, 41,
265–279; g) Z. S. Yoon, A. Osuka, D. Kim, Nat. Chem. 2009, 1, 113–122;
h) Y. Pareek, M. Ravikanth, T. K. Chandrashekar, Acc. Chem. Res. 2012, 45,
1801–1816; i) S. Saito, A. Osuka, Angew. Chem. Int. Ed. 2011, 50, 4342–
4373; Angew. Chem. 2011, 123, 4432.
a) L. Latos-Grazynski in Core-Modified Heteroanalogues of Porphyrins and
Metalloporphyrins, vol. 2 (“Heteroporphyrins, Expanded Porphyrins and
Related Macrocycles”) (Eds.: K. M. Kadish, K. M. Smith, R. Guilard), Aca-
demic Press, San Diego, 2000, pp. 361–416; b) P. J. Chmielewski, L. Latos-
Grazynski, Coord. Chem. Rev. 2005, 249, 2510–2533; c) I. Gupta, M. Ravi-
kanth, Coord. Chem. Rev. 2006, 250, 468–518; d) T. D. Lash, Eur. J. Org.
Chem. 2007, 5461–5481; e) C. Brückner, J. Akhigbe, L. Samankumara in
Syntheses and Structures of Porphyrin Analogues Containing Non-pyrrolic
Heterocycles, vol. 31 (Eds.: K. M. Kadish, K. M. Smith, R. Guilard), World
Scientific, River Edge, NY, 2014, pp. 1–276.
[3]
[4]
[5]
a) J. Akhigbe, G. Peters, M. Zeller, C. Brückner, Org. Biomol. Chem. 2011,
9, 2306–2313; b) J. Akhigbe, J. P. Haskoor, J. A. Krause, M. Zeller, C. Brück-
ner, Org. Biomol. Chem. 2013, 11, 3616–3628.
S. Kai, M. Suzuki, Y. Masaki, Tetrahedron Lett. 1998, 39, 4063–4066.
[6] R. Böhme, E. Breitmaier, Synthesis 1999, 2096–2102.
[7] a) M. Nicolau, B. Cabezón, T. Torres, J. Org. Chem. 2001, 66, 89–93; b) F.
Fernandez-Lazaro, A. Sastre, T. Torres, J. Chem. Soc., Chem. Commun.
1994, 1525–1526; c) M. Nicolau, B. Cabezón, T. Torres, Coord. Chem. Rev.
1999, 190–192, 231–243.
[8] a) M. Toganoh, H. Furuta in Synthesis and Metal Coordination of N-Con-
fused and N-Fused Porphyrinoids, vol. 2 (Eds.: K. M. Kadish, K. M. Smith,
R. Guilard), World Scientific, Singapore, 2010, pp. 295–367; b) M. To-
ganoh, H. Furuta, Chem. Commun. 2012, 48, 937–954.
[9] a) T. D. Lash, A. M. Young, A. L. Von Ruden, G. M. Ferrence, Chem. Com-
mun. 2008, 6309–6311; b) A. M. Young, A. L. Von Ruden, T. D. Lash, Org.
Biomol. Chem. 2011, 9, 6293–6305.
[10] a) L. K. Frensch, K. Proepper, M. John, S. Demeshko, C. Brückner, F. Meyer,
Angew. Chem. Int. Ed. 2011, 50, 1420–1424; Angew. Chem. 2011, 123,
1456; b) L. K. Blusch, Y. Hemberger, K. Pröpper, B. Dittrich, F. Witterauf,
M. John, G. Bringmann, C. Brückner, F. Meyer, Chem. Eur. J. 2013, 19,
5868–5880.
[20] M. Gouterman in Optical Spectra and Electronic Structure of Porphyrins
and Related Rings, vol. 3 (Ed.: D. Dolphin), Academic Press, New York,
1978, pp. 1–165.
[21] a) G. Zarate, MS Thesis, University of Connecticut, 2010; b) M. L. Dean,
Ph. D. thesis, University of Connecticut, 2011.
[22] L. P. Samankumara, S. Wells, M. Zeller, A. M. Acuña, B. Röder, C. Brückner,
Angew. Chem. Int. Ed. 2012, 51, 5757–5760; Angew. Chem. 2012, 124,
5856.
[23] J. K. MacAlpine, R. Boch, D. Dolphin, J. Porphyrins Phthalocyanines 2002,
6, 146–155.
Received: November 14, 2015
[11] J. Akhigbe, C. Brückner, Eur. J. Org. Chem. 2013, 3876–3884.
Published Online: January 20, 2016
Eur. J. Org. Chem. 2016, 992–998
www.eurjoc.org
998
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim