New synthetic pathway leading to oxospirochlorins

Article abstract of DOI:10.1039/c8ra02445f

In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and inverse electron demand Diels-Alder (iEDDA) cyc

Full text of DOI:10.1039/c8ra02445f

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New synthetic pathway leading to
oxospirochlorins†
Cite this: RSC Adv., 2018, 8, 21354
a
a
Justyna S´niechowska, Piotr Paluch,a Tomasz Pawlak,
Grzegorz D. Bujacz,b
*
Witold Danikiewiczc and Marek J. Potrzebowski
*
a
In this work we propose a completely new approach for the synthesis of spirochlorin derivatives based on
the use of an imino-keto intermediate formed in situ from 2-amino-5,10,15,20-tetraphenylporphyrins and
inverse electron demand Diels–Alder (iEDDA) cycloaddition with 3,6-di-2-pyridyl-1,2,4,5-tetrazine. The
mechanism of reaction was analyzed employing theoretical methods by comparing the difference in
energy of Frontier Molecular Orbitals (FMO) for appropriate reagents. Ground-state molecular
electrostatic (ESP) potential maps were employed as additional tools allowing explanation of the
reactivity of substrates. The new class of spirochlorin compounds was fully characterized by means of
mass spectrometry, IR, liquid and solid state NMR and X-ray crystallography. Correlation between
molecular structure and optical properties for the obtained title compounds is discussed.
Received 20th March 2018
Accepted 4th June 2018
DOI: 10.1039/c8ra02445f
rsc.li/rsc-advances
motivation for development of new methods of synthesis, which
may open routes to production of attractive chlorin derivatives
Introduction
with unique properties.
Porphyrinoids are a large group of macrocyclic heteroorganic
compounds ubiquitous in nature. They play very important
roles in multiple biological processes including cell respiration
(hemoglobin), detoxication of xenobiotics, oxygen transport
and the photosynthesis process.1 Chemical modications of
natural and synthetic porphyrinoids have been an area of
intense interest for a number of scientic groups. Development
of methods for structural transformations of the porphyrin
macrocycle can provide a wide spectrum of new functional
materials. Among the big family of porphyrinoid derivatives,
To the group of weakly recognized species with great appli-
cation potential belong the spiro derivatives of chlorins (Fig. 1)
which play key roles in nature. The naturally occurring chlorin
with a spiro motif integral to pyrroline ring is heme d, which
contains a spirolactone unit. During last decade signicant
efforts have been made toward the development of effective
methods for obtaining of this class of compounds. According to
the literature, most synthetic procedures leading to spiro-
chlorins are based on reactions with use of gem-dialkylgroups.4
Kenner and co-workers found that acetamidoethylporphyrins
can be converted into spirochlorins by phosphoryl chloride
treatment in pyridine.5 Smith and colleagues described that
spiroketochlorins can be obtained with high yields from
porphyrin bearing a butyramide group.6 Kai and Suzuki
chlorins (hydrochlorins) are
a very important class of
compounds due to their applicability in photodynamic therapy
and diagnostics, catalysis, materials science, electronics and
solar energy conversion.2 They have unique spectroscopic,
optical and electronic properties and absorb light strongly in
the near infrared part of the electromagnetic spectrum.3 From
a chemical point of view an important issue is the fact that the
physical features of porphyrinoids can be modied and tailored
by changing their molecular structure. Hence, there is still great
aCentre of Molecular and Macromolecular Studies, Polish Academy of Sciences,
Sienkiewicza 112, 90-363 Lodz, Poland. E-mail: jsniech@cbmm.lodz.pl; marekpot@
cbmm.lodz.pl
bInstitute of Technical Biochemistry, Lodz University of Technology, Stefanowskiego 4/
10, 90-924 Lodz, Poland
cInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224
Warsaw, Poland
† Electronic supplementary information (ESI) available: Characterization data for
new compounds: NMR, ESI-MS, IR spectra, UV-VIS, crystal and structure details
for 6a and supplementary theoretical studies. CCDC 1573589. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c8ra02445f
Fig. 1 Structures of some spiro derivatives of chlorins.
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Scheme 1 Synthesis of compounds 3a–3f and 4a–4f.
prepared a spirochlorin by the reaction of tetracyanoetylene ESI MS measurements has been already observed in one of our
with bromovinylheptaetylporphyrin.7 Spirolactones can be ob- groups.16 Additional experiments showed that they are oxidized
tained in reaction of vinyl porphyrins with hydrobromic acid most likely by the atmospheric oxygen and the porphyrinoid
and subsequent ve-step procedure striving to intermolecular itself serves as the photosensitizer of this reaction.
cyclization of propionate side chain.8
Further proof conrming formation of compounds 3a–3f is
In this work we propose a new approach for the synthesis of found by testing their chemical reactivity, in particular in the
spirochlorin derivatives based on use of imino-keto interme- Diels–Alder (DA) cycloaddition. In this reaction the distribution
diate as reagent in inverse electron demand Diels–Alder reac- of electron densities for both reagents is crucial. In a DA with
tion (iEDDA). The starting point for development of our strategy normal electron demand, the dienophile typically bears an
is an observation reported over 30 years ago by Crossley and electron-withdrawing group (EWG), while the diene is electron-
King9 who found that 2-amino-5,10,15,20-tetraphenylporphyrin rich.17 Reversely, the iEDDA reaction is characterized by an
2a easily undergoes photo-oxidation forming compound 3a, electron-poor diene and an electron-rich dienophile.18
which further on silica gel immediately undergoes hydrolysis to Compounds 3a–3f fulll prerequisites expected for electron-rich
dioxochlorin 4a (Scheme 1).10 On the course of our studies we dienophiles.
have noticed that compounds 3a–3f can be obtained under mild
In our synthetic strategy the choice of diene is decisive. Very
conditions, they are relatively stable and can be thought as recently Mayer and Lang have reviewed the different aspects of
active in situ precursors in chemical reactions. To the best of our tetrazines in iEDDA cycloadditions and theirs applications in
knowledge to date this compound was not considered as synthesis of biological products.19 As reported 1,2,4,5-tetrazines
a substrate in chemical synthesis. In our researches, we report containing strong EWG substituents are reactive species,
the use of compounds 3a–3f in reaction with tetrazine to obtain commonly used in iEDDA.18–20 Due to their high reactivity these
new oxospirochlorins. The method reported herein is yield and compounds are still of synthetic interest to organic chemists.
efficient, can be employed for synthesis of novel functionalized Increase of the electron-withdrawing character of groups in 3,6
spiro derivatives with desired spectroscopic properties. Thus, position in 1,2,4,5-tetrazine (e.g. pyridyl, CO2Me etc.) increased
this reaction is a tool for preparing new dyes, scaffolds based on the reactivity of the diene. In this project we have used 3,6-di-2-
porphyrins and chlorins, molecular receptors and a biomimetic pyridyl-1,2,4,5-tetrazine 5 (Scheme 2), because it has an ability
models of heme or another systems imitating the active sites of to react as inverse electron demand diene. The compound 5 was
some enzymes.
synthesized from commercially available 2-pyridinecarbonitrile
and hydrazine hydrate in a two-step procedure.21 Treatment of
compounds 3a–3f generated in situ from 2a–2f solvent
dramatically vary the reaction course. Formation of the oxo-
spirochlorins 6a–6f was not observed when acetonitrile or
dichloromethane were used as a solvents. We cannot exclude
that in this case the high boiling point of toluene is critical
Results and discussion
Synthesis of oxospirochlorins
The starting material, b-nitro porphyrin derivatives 1a–1f were
obtained employing known procedure consisting several steps
which include the synthesis of porphyrins from appropriate
aldehyde and pyrrole;11 complexation reaction between
porphyrin and copper acetate;12 nitration at b-position with
copper(II) nitrate in mixture acetic acid/acetic anhydride.13 The
key step in synthesis of b-amino porphyrins 2a–2f is deme-
tallation reaction14 of 1a–1f and the reduction of nitro group
with SnCl2 in hydrochloric acid.10,15 The formation of 2a and 3a
were conrmed by mass spectrometry. The rst hint that b-
amino porphyrins 2a–2f are readily oxidized came from the
routine ESI mass spectrum of the amine 2a (R ¼ C6H5) recorded
in acetonitrile (Fig. 2). Together with expected m/z 630.5 peak
corresponding to the protonated amine 2a, an intense m/z 644.5
peak has been observed. An accurate mass measurement
revealed the molecular formula C44H30N5O, which differs from
the amine 2a by two lacking hydrogen atoms and one additional
Fig. 2 ESI mass spectrum of the acetonitrile solution of 2a. m/z 315.9
oxygen atom. Spontaneous oxidation of porphyrinoids during peak corresponds to the [M + 2H+]2+ ion of 2a.
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Analysis of cycloaddition employing theoretical calculations
In the previous section we presented intuitive arguments which
enable us to assume that reaction under investigation is clas-
sied as iEDDA despite that the substrates 3a–3f can be also
thought as an electron decient dienophile (double bond C]
NH conjugated with a C]O group) and the 3,6-di-2-pyridyl-
1,2,4,5-tetrazine 5 looks like an electron rich diene. In this
section we provide proofs, based on theoretical approach which
conrm our hypothesis. One of the main differences between
classical DA and iEDDA reaction is dened trough analysis of
frontier molecular orbitals (FMOs).22 In the iEDDA cycloaddi-
tion the azadiene has a highly stabilized HOMO orbital with
energy below HOMO of dienophile (it is reverse situation
comparing to nonpolarized DA reaction). It leads to decrease of
energy gap between LUMO diene orbital and HOMO dienophile
and signicant electron delocalization from the dienophile to
the azadiene with concomitant energy stabilization. This single
FMO interaction is assumed to more than compensate for the
increase in the forward FMO energy gap between the azadiene
HOMO and the dienophile LUMO. Trough analysis of our
computational data shown in Fig. 3 and Table 2 the mechanism
of interaction between 3a–3d and 5 can be dened as iEDDA
reaction. As seen HOMO dienophile-LUMO diene gap marked
by dashed line arrows is signicantly lower compared to
opposite situation. Lack of formation of product in case of
sample 3e can be explained on the ground of FMO. The situa-
tion with 3f is more complicated because the unfavorable steric
effect of 2,6-diuorophenyl group most likely exceeds adequate
character of HOMO–LUMO gap.
Another fast and convenient approach for analysis of the
preference for cycloaddition is taking into account electrostatic
potential (ESP) maps of studied models and evaluating the
relative electron population of the atoms in imino-keto inter-
mediates 3a–3f involved in bond formation during the reac-
tion.23 Fig. 4 displays ESP maps for studied models which may
be used to qualitative prediction the reactivity of the active sites
of compounds 3a–3f. This strategy provides a useful device of
relative wave function amplitude and electron density. Molec-
ular ESPs are also advantageous because they are generally not
highly computational method and basis set dependent. The
electrostatic potentials at the surface are illustrated by different
colors. While the yellow to red color parts point out the regions
of negative electrostatic potential, the blue sites represent the
Scheme 2 Synthesis of oxospirochlorins 6a–6f.
Table 1 Comparative reactivity and product yields of b-amino meso-
tetraarylporphyrins 2a–2f with tetrazine 5
Porphyrin
Tetrazine
Product
Yield [%]
2a
2b
2c
2d
2e
2f
5
5
5
5
5
5
6a
6b
6c
6d
6e
6f
50
38
32
25
—
—
parameter. Moreover, we tested the reactivity of compound 4a
in the iEDDA reaction. Reaction of with equimolar amount of
tetrazine 5 in reuxing toluene for 5 hours gave oxospiro-
chlorins in 25–50% yields. Obtained products were isolated and
puried by column chromatography. It has to be stressed that
change of the 4a with tetrazine 5 carried out boiling toluene
does not lead to the new product.
To test a generality of this process, we carried out reaction
under the same conditions as mentioned above, using
porphyrins containing different substituted aryl rings in meso
position (Table 1). Steric and electronic character of groups in
meso position inuence the reactivity of the porphyrins as
dienophile. The use of porphyrin, which is sterically hindered in
reactive site, gave no product of reaction, even with longer
heating time.
A plausible mechanism for the cycloaddition reaction is
proposed in Scheme 3. The imino-keto intermediates 3 react
with tetrazine 5 to give a transition state A and form the highly
strained intermediate B. It has not been observed, because it
instantly undergo a retro Diels–Alder step, which is responsible
for the elimination of dinitrogen. The termination step of the
reaction is hydrogen shi from compound C and compound D
are formed.
Scheme 3 Plausible mechanism.
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Fig. 3 Comparison of FMO Energies for studied pair of diene (5) and dienophiles 3a (a), 3b (b), 3c (c), 3d (d), 3e (e) and 3f (f).
for electrophilic attack (reactive site of dienophile in the iEDDA
cycloaddition).
Table 2 Numerical results of calculated FMO energies (HOMO and
LUMO)
Finally we wish to comment the last stage of synthetic
pathway, leading from C to D (see Scheme 3) related with pro-
totropic migration and formation of new thermodynamically
stable tautomer. The question about reversibility of this process
is justied. Our theoretical calculations of ground state energy
for C and D shows signicant difference between both forms.
For D energy is lower ca. 74 kJ molꢀ1. Thus we can conclude that
this process is irreversible.
Energy [kJ molꢀ1
HOMO
]
Compound
LUMO
5
ꢀ23.49
ꢀ20.30
ꢀ19.78
ꢀ19.40
ꢀ22.35
ꢀ23.61
ꢀ21.11
ꢀ9.50
3a
3b
3c
3d
3e
3f
ꢀ10.56
ꢀ10.19
ꢀ10.03
ꢀ12.50
ꢀ13.71
ꢀ11.18
Spectral and structural analysis of oxospirochlorins in the
liquid and solid phases
regions of positive electrostatic potential and the parts with
green color indicate the regions of close zero potential. In the
ESP maps, one of the most negative region is located on the ]
N–H group which can be considered as the most preferred site
The obtained title derivatives are new class of compounds hence
their structure had to be proved in a doubtless manner. In the
rst approach, for structure analysis we employed techniques:
NMR spectroscopy, UV-VIS and high-resolution mass
spectrometry.
The absorption spectra of synthesized oxospirochlorins 6a–
6d were measured in dichloromethane at room temperature.
Fig. 5 shows the spectra and the band maxima of absorption
and log excitation coefficients (see Table 3). Similarly to others
porphyrinoids, in the absorption spectrum it can be indicated
Soret band and Q-bands. The position of the Soret bands and Q
bands are nearly identical with each other. The slightly bath-
ochromically shied Soret bands for 6b and 6c, and hyp-
sochromatically shied for 6d have higher excitation
coefficients (log 3l ¼ 5.58; 5.49 and 5.52, respectively) as
max
compared to oxospirochlorin 6a (log 3l ¼ 5.29). The spectra of
max
synthesized compounds 6a–6d are different from spectrum of
a typical tetraarylchlorin. For each sample the intensity of the
red absorption band is much smaller than observed for chlor-
ins. The difference in the absorption prole is associated with
the existence of being of p-electron conjugation with the
carbonyl group. This b-functionalization of chlorins renders the
absorption spectrum neither chlorin-like. This electronic
Fig. 4 Comparison of ground-state molecular electrostatic potentials
(ESPs) for studied models 3a (a), 3b (b), 3c (c), 3d (d), 3e (e), 3f (f) and 5
(g) plotted from ꢀ0.03 (red) to +0.3 (blue) Hartree. Violet arrows
marked the reaction sites for imino-keto intermediates.
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conrmed by 1D and 2D NMR measurements. The 1H NMR
spectrum contains two broad singlets near ꢀ2 ppm for the NH
protons in typical for porphyrinoids region. In the 13C NMR
spectrum (Fig. 6a) of compound 6a the most diagnostic and
characteristic signals for the carbonyl carbon atom is observed
at 202 ppm and the spiro carbon atom at 68 ppm. Moreover, the
1H–15N HSQC spectrum displays a singlet at 141.5 ppm corre-
sponding to the imino NH group. These results conrm the
structure of obtained compound 6a. The low symmetry of
compound 6a removes the equivalency of the four meso-phenyl
rings. In the 1H–13C HSQC spectrum not equivalent pyridyl
rings are seen and recognized.
As in the case of almost all porphyrin derivatives, the ob-
tained spirochlorins are solid. Testing the precipitated sample
of 6a by means of 13C solid state NMR spectroscopy we were
rather surprised by the quality of spectrum (Fig. 6c). Relatively
sharp 13C signals suggest the signicant contribution of crys-
talline phase in whole sample. Fig. 6 shows 13C NMR spectra
with clearly seen characteristic resonances.
Fig. 5 UV-VIS absorption spectra (CH2Cl2) at room temperature of
obtained oxospirochlorins 6a–6d. lexcitation ¼ lSoret
.
Table 3 Excitation coefficients of the oxospirochlorins 6a–6d
This promising observation, proving tendency of sample for
crystallization, prompted us to focus on growing the single
crystals with quality suitable for X-ray crystallographic studies.
Solid state NMR was found to be a tool supporting optimization
of crystallization process.26 It has to be stressed that to date
deposited X-ray structures for spirochlorins do not exist in
available crystallographic data bases.
log 3l
in dichloromethane
max
Compound
lmax [nm]
6a
6b
6c
6d
429
430
432
426
5.29
5.58
5.49
5.52
Testing different approaches we have found that the best
option for growing 6a crystals is recrystallization of compound
by isothermal evaporation of dichloromethane at room
temperature. The crystal structure and molecular packing of 6a
is shown in Fig. 7. The structural information are attached as
ESI.† The compound 6a crystallizes in triclinic form in centro-
inuence of the carbonyl group is also observed in the UV-VIS of
dioxochlorins 4a.24 Despite of broadened Q-bands the
compound 4a was classied as chlorin.24b,25
The obtained compounds were also characterized by mass
spectrometry and NMR spectroscopy (see ESI† for original
spectra). The ESI-MS spectra of 6a show the molecular ion peak
at m/z 852.5 [M + H+]+ together with [M + H+ ꢀ H2O]+ and [M +
H+ ꢀ CO]+ fragment peaks. The presence of the carbonyl group
in 6a is conrmed by 1725 cmꢀ1 absorption band in the IR
spectrum. The structure of oxospirochlorin 6a was further
ꢀ
symmetric P1 space group. The independent unit contains one
molecule of 6a and one molecule of crystallization solvent,
dichloromethane. Two independent units related by center of
symmetry ll unit cell. The molecules of 6a interact in crystal
lattice mostly by hydrophobic contacts. The two solvent mole-
cules are located in cage created by network of 6a. They are
related by symmetry and interact with each other. The contacts
with host molecule are by weak hydrogen bond between carbon
hydrogen and ketone oxygen atoms and van der Waals contact
of disordered C7 atom with disordered phenyl ring. In both
positions carbon hydrogen atoms of dichloromethane with
fractional occupancy are able to create contacts.
In the unit cell, molecule of 6a contains two main approxi-
mately planar systems perpendicular to each other. One of them,
the chlorin ring, is connected with the other the 1,2,4-triazine ring,
by a spiro C7 atom. The tetra phenyl chlorin moiety is slightly
bound around the axis passing through the N2, N4 unprotonated
nitrogen atoms. Two of four phenyl rings connected to the chlorin
ring located in the vicinity of the modied pyrrole ring are
perpendicular to it, while the other two, more distant from the
modication, are angular. The disordered phenyl is parallel to the
1,2,4-triazine ring and the short distance between these two
aromatic systems allows p–p interaction. One of the two pyridin-2-
yl rings connected to the triazine ring is approximately coplanar
with it and the other is slightly twisted. Only two nitrogens of the
Fig. 6 13C NMR spectra for sample 6a. (a) liquid sample dissolved in
chloroform-d, (b) amorphous solid sample recorded employing 13C
CP/TOSS MAS technique with spinning rate 8 kHz. (c) Precipitated solid
sample recorded employing 13C CP/TOSS MAS technique with spin-
ning rate 8 kHz.
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Fig. 7 Crystal structure of obtained compound 6a (left) and unit cell (right).
chlorin ring are protonated the positions of them were found from methods.21 b-Nitro porphyrins 1a and 1b were prepared
experimental data. The low no restricted isotropic thermal following the reported procedures.11–15a,27
parameters and stabile position during renement indicate that NMR experiments were run on a 600 MHz Bruker Avance III
even at room temperature external proton exchange between spectrometer equipped with BBOF probhead operating at
1
nitrogen atoms doesn't occurs in a crystal.
600.13, 564.69, 150.92 MHz for H, 19F and 13C nuclei, respec-
tively and 500 MHz Bruker AVANCE DRX. The following
abbreviations were used to describe peak splitting patterns
when appropriate: s ¼ singlet, d ¼ doublet, t ¼ triplet, dd ¼
doublet of doublets, ddd ¼ doublet of doublet of doublets and
m ¼ multiplet. Coupling constants J are reported in Hz.
UV-VIS spectra were obtained on Specord S600 “Analytyk
Jena”. Mass spectra of obtained compounds were registered by
MALDI-TOF Mass Spectrometer – PerSeptive Biosystems and,
additionally, on Synapt G2S HDMS (Waters) and 4000 Q TRAP
(Sciex) mass spectrometers.
Conclusions
In conclusion, novel and efficient synthesis of a series of oxo-
spirochlorin derivatives has been achieved via the iEDDA reac-
tion from b-substituted porphyrins and 1,2,4,5-tetrazine in
reasonable yield. We revealed, that yield of reaction depends on
the structure of substrates, position of the substituents in the
meso ring and theirs electronic characters. The experimental
data were explained by means of theoretical methods
comparing the difference in energy of Frontiers Molecular
Orbitals (FMO) for appropriate substrates. Ground-state
molecular electrostatic (ESP) potential maps were employed as
an additional tools allowing to describe the reactivity of
substrates. Our experimental and computer results revealed
that placing of atoms or groups in ortho position due to steric
effect obstructs reactivity of system and in consequence the
desired spiro product is not formed. The obtained compounds
were fully characterized by spectroscopic methods. This reac-
tion can be an excellent tool for preparing a novel chlorin
derivatives. The method discovered in this work allows access to
the libraries of compounds containing a tetrapyrrolic systems.
Theoretical calculations
All calculations in this work have been performed using Gaussian
16 (G16) program package.28 Starting geometries of molecules
were generated de novo and minimized in vacuo using the hybrid
Hartree–Fock/density functional theory (HF/DFT) method
PBE1PBE (named also as PBE0)29 and the 6-311+G(d,p) basis set.30
The geometry was always optimized without any symmetry
restrictions. Each stationary point was characterized by calcu-
lating the harmonic vibration frequencies in order to verify that
they have no imaginary frequency. The distributions and energy
levels of HOMO and LUMO orbitals as well as molecular elec-
trostatic potential (ESP) map properties of the studied
compounds are calculated using the same methodology.
For optimized structures the energy gaps was also calculated
using LC-uHPBE functional (which is recommended version of
the long-range-corrected uPBE functional by G16),31 and aug-cc-
Experimental
Materials and methods
The compounds were prepared using chemicals which were pVTZ basis set.32 Such choice was made because it is well known
purchased from Sigma Aldrich, TCI and used without further that in DFT calculations, with common approximations used in
purication. Reagent grade solvents were purchased from the functionals is oen not useful in practice. In other hand
Polish Chemicals Reagents and were distilled prior to use. Silica DFT is a compromise which allows for a treatment of quite large
gel columns for chromatography were prepared with silica systems what would not be allowed using computationally more
(Kieselgel 60, 200–400 mesh). 5,10,15,20-tetraphenylporphyrin demanding methods.33 Recent papers shown that this weakness
and
5,10,15,20-tetra(pentauorophenyl)porphyrin
were can be restored by using long-range corrected hybrid func-
purchased from PorphyChem. 3,6-di-2-pyridyl-1,2,4,5-tetrazine tionals where the HOMO and LUMO eigen values obtained from
5 is known compound which was prepared according previous this new class of functionals have been demonstrated to be very
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accurate. It is found that tuned LC-uPBE provides very small TOF) m/z 990.8 [M + H]+; compound 2f MS (MALDI TOF) m/z
error that clearly improve upon standard exchange-correlation 774.6 [M + H]+.
functionals.34 The results for LC-uHPBE functional and aug-
cc-pVTZ are presented in ESI† and shows the same tendencies
as for PBE1PBE/6-311+G(d,p) level.
General procedure for synthesis of oxospirochlorins
In round bottom ask a toluene (15 mL) solution of the b-amino
porphyrin 2a–2f (0.18 mmol) and 3,6-di-2-pyridyl-1,2,4,5-
tetrazine 5 (0.18 mmol, 0.043 g) was heated at reux for 5 h
with TLC monitoring (eluent: CHCl3). Aer being cooled to
room temperature and evaporated, the reaction mixture was
applied on the top of a silica gel column. Purication of the
purple-brown coloured product using column chromatography
and CHCl3 as eluent afforded the desired oxospirochlorin
product as a dark purple colored solid.
Single crystal X-ray measurements
Single crystal diffraction experiments for 6a were carried out on
Oxford SuperNova single-crystal diffractometer with micro
source CuKa radiation (l ¼ 1.5418 A) and a Titan detector. The
˚
plate crystal of dimensions 0.18 ꢁ 0.09 ꢁ 0.02 was glued do
a glass capillary by epoxy glue and measured at room temper-
ature. The absorption correction was performed based on the
crystal shape, orientation and absorption coefficient. Diffrac-
tion data collection, cell renement, data reduction, and
absorption correction were performed using the CrysAlis PRO
program (Oxford Diffraction). The structure was solved by direct
methods SHELXS and rened using full-matrix least-squares
methods SHELX 2015 implemented in OLEX2 package.35 The
hydrogen atoms ware set geometrically and rened as riding
with the thermal parameter equal to 1.2 of the thermal vibration
of the parental atom. The two hydrogen atoms connected with
internal nitrogen atoms of the chlorin ring were found on the
difference Fourier map and rened without any geometrical
restrains with isotropic thermal parameters. Two disordered
moieties were detected in the structure: the phenyl ring in the
vicinity of 1,2,4-triazine ring and a solvent dichloromethane
molecule. Both disordered fragments were modeled in two
positions with the fractional occupation factors summing to
one. The vibration of phenyl ring can be described as a swing of
the pendulum in the ring plane. The dichloromethane molecule
oscillates around the axis passing thought the Cl1 atom and the
middle of the C60–Cl2 bond. The structure was validated by
CheckCif (http://checkcif.iucr.org) and deposited to the Cam-
bridge Crystallographic Data Centre (CCDC) under accession
number 1573589.
Compound 6a. 0.083 g, yield: 50%, 1H NMR (600 MHz,
CDCl3): d ꢀ2.08 (s, 1H), ꢀ1.86 (s, 1H), 6.66–6.72 (m, 1H), 7.02 (d,
J ¼ 4.4 Hz, 1H), 7.12 (d, J ¼ 7.3 Hz, 1H), 7.23 (dd, J ¼ 18.5,
11.0 Hz, 1H), 7.36–7.29 (m, 1H), 7.43 (t, J ¼ 7.5 Hz, 1H), 7.47–
7.71 (m, 17H), 7.91 (t, J ¼ 18.6 Hz, 1H), 8.08–8.22 (m, 6H), 8.55–
8.64 (m, 5H), 8.78 (d, J ¼ 4.6 Hz, 1H), 9.59 (s, 1H). 13C NMR (151
MHz, CDCl3): d 68.4, 114.6, 115.8, 120.4, 121.4, 121.7, 123.3,
123.4, 125.4, 126.6, 126.6, 126.6, 126.7, 126.9, 126.9, 127.2,
127.3, 127.4, 127.6, 127.8, 127.8, 127.9, 127.9, 132.4, 132.9,
133.1, 133.7, 133.8, 134.1, 134.2, 134.2, 134.3, 134.4, 135.7,
136.6, 136.7, 137.3, 139.7, 140.6, 141.2, 141.4, 141.9, 141.9,
142.3, 144.2, 146.0, 146.7, 148.1, 149.6, 153.3, 153.7, 154.7,
161.9, 201.9. HRMS (ES+/TOF) m/z: [M + H]+ calcd for C56H38N9O
852.3199; found 852.3200, MS (MALDI TOF) m/z 853.1 [M + H]+.
Compound 6b. 0.058 g, yield: 38%, 1H NMR (600 MHz,
CDCl3): d ꢀ2.10 (s, 1H), ꢀ1.88 (s, 1H), 6.61–6.69 (m, 1H), 6.88–
6.99 (m, 3H), 7.20–7.59 (m, 10H), 7.62–7.87 (m, 4H), 7.87–8.02
(m, 3H), 8.05 (d, J ¼ 27.9 Hz, 1H), 8.52–8.69 (m, 5H), 8.77 (dd, J
¼ 4.8, 1.4 Hz, 1H), 9.57 (s, 1H). 13C NMR (151 MHz, CDCl3):
d 68.4, 114.3, 115.7, 120.3, 121.3, 121.5, 123.2, 123.3, 125.2,
126.7, 126.5, 127.1, 127.2, 127.4, 127.5, 127.6, 127.8, 128.0,
132.2, 132.7, 131.0, 133.5, 133.5, 133.9, 134.1, 134.3, 136.5,
136.6, 136.7, 136.7, 137.2, 137.3, 137.4, 137.5, 138.2, 139.0,
140.5, 141.4, 142.3, 144.1, 145.9, 146.6, 147.9, 149.6, 153.2,
153.6, 154.7, 161.8, 202.1. HRMS (ES+/TOF) m/z: [M + H]+ calcd
General procedure for synthesis of b-amino porphyrins 2a–2f
b-Amino porphyrins 2a–2f were prepared in accordance to for C60H46N9O 908.3825; found 908.3833, MS (MALDI TOF) m/z
a previously described method,15a with slight modication. b- 909.2 [M + H]+.
Nitro porphyrin 1a–1f (0.22 mmol) was dissolved in a concen-
Compound 6c. 0.045 g, yield: 32%, 1H NMR (600 MHz,
trated HCl (15 mL) at room temperature. Aerwards, SnCl2- CDCl3): d ꢀ2.09 (s, 1H), ꢀ1.87 (s, 1H), 3.97–4.09 (m, 15H), 6.60–
$2H20 (1 mmol, 0.226 g) was added. The resultant dark green 6.80 (m, 2H), 6.94–7.01 (m, 4H), 7.07–7.48 (m, 1H), 7.30–7.32
coloured mixture was heated at 65 ꢂC for 2 h with stirring. The (m, 5H), 7.48–7.56 (m, 3H), 7.67 (dd, J ¼ 8.3, 2.1 Hz, 1H), 7.79–
mixture was then cooled to room temperature and H2O was 7.83 (m, 4H), 7.96–8.25 (m, 9H), 8.53–8.64 (m, 6H), 8.76–8.77
added. The aqueous layer was extracted with CH2Cl2. The (m, 1H), 9.59 (s, 1H). 13C NMR (151 MHz, CDCl3): d 68.4, 111.7,
combined organic layers were washed with saturated 112.1, 112.3, 112.3, 112.7, 113.9, 115.3, 120.3, 121.2, 121.3,
NaHCO3(aq), before being dried over anhydrous K2CO3/MgSO4, 123.0, 123.2, 125.3, 126.3, 126.4, 127.4, 127.8, 132.0, 132.9,
ltered and concentrated to dryness in vacuo. The dark purple 133.3, 133.5, 133.5, 133.9, 134.3, 134.7, 135.0, 135.2, 135.6,
colored solid was used without purication. The formation of 136.6, 136.8, 137.4, 140.8, 141.7, 142.3, 144.2, 145.9, 146.6,
described compounds were conrmed by mass spectrometry. 147.9, 149.6, 153.2, 153.8, 154.9, 159.0, 159.2, 159.4, 159.5,
The attempts to isolation of compounds 2a–2f no give a pure 161.9, 202.2. HRMS (ES+/TOF) m/z: [M + H]+ calcd for
products. Compound 2a: MS (MALDI TOF) m/z 630.8 [M + H]+;
C66H46N9O5 972.3622; found 972.3629, MS (MALDI TOF) m/z
compound 2b MS (MALDI TOF) m/z 686.8 [M + H]+; compound 973.1 [M + H]+.
2c MS (MALDI TOF) m/z 750.7 [M + H]+; compound 2d MS
Compound 6d. 0.032 g, yield: 25%, 1H NMR (600 MHz,
(MALDI TOF) m/z 902.7 [M + H]+; compound 2e MS (MALDI CDCl3): d ꢀ2.18 (s, 1H), ꢀ1.98 (s, 1H), 6.67 (ddd, J ¼ 7.2, 5.0,
21360 | RSC Adv., 2018, 8, 21354–21362
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1.0 Hz, 1H), 6.94 (d, J ¼ 4.4 Hz, 1H), 7.15 (dd, J ¼ 14.2, 7.2 Hz,
1H), 7.20–7.36 (m, 2H), 7.42 (m, 1H), 7.52 (ddd, J ¼ 15.7, 9.8,
1.7 Hz, 2H), 7.70 (d, J ¼ 6.5 Hz, 1H), 7.75–7.85 (m, 5H), 7.92–8.03
(m, 6H), 8.12–8.30 (m, 6H), 8.46 (d, J ¼ 4.6 Hz, 1H), 8.51–8.55
(m, 3H), 8.60 (d, J ¼ 4.3 Hz, 1H), 8.71 (dd, J ¼ 4.9, 1.5 Hz, 1H),
9.64 (s, 1H). 13C NMR (151 MHz, CDCl3): d 68.1, 113.6, 114.6,
120.3, 120.4, 121.1, 121.9, 123.5, 123.5, 123.6, 123.7, 123.9,
123.9, 124.0, 124.2, 124.4, 125.3, 125.4, 125.5, 125.6, 126.6,
126.7, 127.7, 128.0, 128.2, 129.0, 132.5, 133.0, 133.3, 133.8,
134.0, 134.0, 134.2, 134.3, 136.1, 136.2, 136.7, 136.9, 137.9,
140.1, 140.8, 141.7, 143.0, 144.3, 144.5, 145.1, 145.1, 146.1,
146.6, 148.3, 149.0, 152.8, 153.4, 154.3, 161.9, 201.4. HRMS
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Conflicts of interest
There are no conicts to declare.
Acknowledgements
This research has been nancially supported by the Polish
National Center of Sciences (Grant No. 2013/11/N/ST5/02040).
The computational resources were partially provided by the
Polish Infrastructure for Supporting Computational Science in
the European Research Space (PL-GRID).
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