3-(Dialkoxyphosphoryl)-N-confused phlorin and porphyrin. Synthesis, stereochemistry, and coordination properties

Article abstract of DOI:10.1021/jo302689d

A 3-phosphonated N-confused phlorin 3 was synthesized by the reaction of N-confused porphyrin 1 and trimethyl or triethyl phosphite 2 in the presence of acetic acid in good yield. The presence of hydrogen and aryl substituents in one of the meso positions (C5) generates a stereogenic center, resulting in configurationally stable enantiomers. The enantiomers were separated by HPLC and characterized by the circular dichroism method for the first time in the case of phlorin. Further oxidation of 3 by DDQ (2,3-dichloro-5,6-dicyano-1,4- benzoquinone) afforded the achiral 3-phosphonated N-confused porphyrin 4. Chiral chlorozinc 4-Zn and chlorocadmium 4-Cd, as well as achiral nickel(II) complexes 4-Ni were also characterized. For 4-Cd in the solid state, formation of a dimer consisting of heterochiral subunits joined by two H-bonds was established by a single crystal X-ray analysis. For 4-Cd, separation of enantiomers was achieved. Slow racemization of 4-Cd in solution prevented the absolute configuration determination by the X-ray method indicating the labile character of the complex. The relationship between circular dichroism and absolute configuration of 3a and 4-Cd was established on the basis of TD-DFT calculations.

Full text of DOI:10.1021/jo302689d

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3‑(Dialkoxyphosphoryl)-N-confused Phlorin and Porphyrin. Synthesis,
Stereochemistry, and Coordination Properties
Bin Liu,† Xiaofang Li,*,† Xin Xu,† Marcin Stępien,‡ and Piotr J. Chmielewski*,‡
́
†Key Laboratory of Theoretical Chemistry and Molecular Simulation of Ministry of Education, Hunan Province College Key
Laboratory of QSAR/QSPR, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology,
Xiangtan, Hunan 411201, China
‡Department of Chemistry, University of Wrocław, 14 F. Joliot-Curie Street, 50 383 Wrocław, Poland
S
* Supporting Information
ABSTRACT: A 3-phosphonated N-confused phlorin 3 was synthesized by the
reaction of N-confused porphyrin 1 and trimethyl or triethyl phosphite 2 in the
presence of acetic acid in good yield. The presence of hydrogen and aryl substituents
in one of the meso positions (C5) generates a stereogenic center, resulting in config-
urationally stable enantiomers. The enantiomers were separated by HPLC and
characterized by the circular dichroism method for the first time in the case of phlorin.
Further oxidation of 3 by DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) afforded
the achiral 3-phosphonated N-confused porphyrin 4. Chiral chlorozinc 4−Zn and
chlorocadmium 4−Cd, as well as achiral nickel(II) complexes 4−Ni were also
characterized. For 4−Cd in the solid state, formation of a dimer consisting of
heterochiral subunits joined by two H-bonds was established by a single crystal X-ray
analysis. For 4−Cd, separation of enantiomers was achieved. Slow racemization of
4−Cd in solution prevented the absolute configuration determination by the X-ray
method indicating the labile character of the complex. The relationship between circular dichroism and absolute configuration of 3a and
4−Cd was established on the basis of TD-DFT calculations.
observation of similar reactivity of carbaporpholactone.41 A related
INTRODUCTION
■
catalytic dialkoxyphosphorylation of β-carbons in a reaction of diethyl
2-Aza-21-carbaporphyrins (N-confused porphyrins, NCP, 1),
phosphite with bromoporphyrins has been very recently reported for
porphyrin isomers containing a pyrrole moiety incorporated to the
regular porphyrins,42 indicating a considerable interest in the
macrocyclic ring by meso-α and meso-β linkages, have attracted
phosphorylated porphyrin systems. Porphyrins with phosphine or
considerable attention in recent years1−3 because of their potential
phosphonate substituents at one or two meso positions have been
applications in catalysis4,5 and molecular sensing6−8 as well as in
shown to form oligomers or networks in which metalloporphyrin
supramolecular,9−12 materials,11,13,14 and medical chemistry.15−18
subunits are linked by P- or O-coordination to the metal ion.43 Thus,
Chemical modification of the macrocycle and coordination chemistry
introduction of such substituents allows not only for fine alteration of
are the two main directions in current research on NCPs. With some
the coordination properties of the macrocyclic interior but also
exceptions, the modifications focus on the confused pyrrole which has
provides an additional donor group on the perimeter.44−47
three main reaction sites, i.e., N2 (external nitrogen),19−23 C3
In our search for new and potentially useful optically active and
(external carbon),23−27 and C21 (internal carbon).28−35 The
reactivity of the C3−N2 bond on the periphery of NCP, which is
partially isolated from the macrocyclic conjugation pathway,
resembles that of a CN fragment in some aza-aromatic systems
configurationally stable systems, we focus on the nonplanar
derivatives of NCP and their complexes which are intrinsically
chiral.48 In this paper, we present for the first time the resolution of
the enantiomers of a chiral phlorin and of a chiral complex of a Group
(quinolines, isoquinolines). Previously, we have shown that in the
12 metal of the NCP derivative.
case of NCP such reactivity results in a regiospecific substitution at C3
by cyclic substrates containing active methylene.25 Formation of
RESULTS AND DISCUSSION
■
phlorin-type products involving N2 and meso-position C20 as targets
NCP (1) was reacted with trimethyl or triethyl phosphite in the
presence of acetic acid in refluxing anhydrous benzene to
produce the desired product 3 in moderate to good yields
(Scheme 1). The reaction also proceeded at room temperature,
though under such conditions a higher molar excess of the
for the 1,3-dipolar agents is also a consequence of that kind of
reactivity.36 Inspired by the known reactivity of pyridines or
isoquinolines toward trialkyl phosphites,37−39 which offers a
convenient route to phosphorylated derivatives, we have decided to
apply a similar protocol in the phosphorylation of NCP. Introduction
of phosphorus-bearing substituents to the position C3 and/or C21 by
the reaction of NCP or its trivalent silver complex with potassium
diphenylphosphide has been recently reported,40 following the
Received: December 10, 2012
Published: January 23, 2013
© 2013 American Chemical Society
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Scheme 1. Synthesis of 3-Phosphorylated N-Confused Phlorins
phosphite 2 was required (about 20-fold). The color of the
solution gradually changed from brown-green to blue-green. The
progress of the reaction was monitored by TLC, and the target
products were purified by flash column chromatography on silica
gel and identified as the 3-phosphorylated N-confused phlorin 3
on the basis of its mass, UV−vis, and NMR (1H, 13C, 31P, COSY,
HSQC, HMBC, NOESY) spectra.
The mass spectrum (MALDI-TOFMS) of 3a revealed the
molecular ion peak at m/z 781, consistent with the addition of a
dimethoxyphosphoryl group to NCP. The UV−vis spectrum of
3 (Figure 1), characterized by two major bands at ∼415 and
with coupling constants 3JHP = 11.5 Hz are those of methoxyls on
the phosphoryl fragment. The upfield shift of the pyrrole signals and
the downfield shift of the 21-CH, 22-NH, and 24-NH peaks indicate
the absence of a macrocyclic aromatic ring current in 3a. In the
13C NMR spectrum of 3a, two doublets at δC 52.9 and 53.1 ppm
(2JCP = 4.7 and 3.9 Hz, respectively) were assigned on the basis of
heteronuclear 2D experiments to the methoxyl carbons of the
phosphonate group and the singlet at δC 41.7 ppm was assigned to
the meso position C5, whereas the doublet at δC 104.8 ppm (4JCP
=
13.2 Hz) was assigned to the internal carbon C21. The 13C−1H
HMBC spectrum allowed an assignment of the C3 signal which is a
doublet centered at δC 112.7 ppm (1JCP = 225.2 Hz). The signal at δP
13.9 in the 31P{1H} NMR spectrum of 3a indicated the presence of a
phosphonate group, while the 31P−1H HMBC experiment
confirmed scalar couplings of phosphorus with neighboring protons.
1
A low-temperature H−1H COSY spectrum (235 K, CDCl3)
confirmed scalar couplings between the “inner” and “outer” protons.
Two NH protons that are located within the macrocyclic ring and
resonate at δH 8.23 and 8.75 ppm correlate with two pairs of
β-pyrrole protons resonating at δH 6.82, 7.03 ppm and at δH 6.68,
6.71 ppm, respectively. The 2-NH located on the confused pyrrole
whose signal appears at δH 9.06 ppm correlates with 21-CH at δH
5.29 ppm. From the low-temperature 1H−1H NOESY experiment
(235 K, CDCl3) indicating through-space interaction between
21-CH and 22,24-NH their common intra-annular location can be
inferred. In addition, correlations of 5-CH with methoxy protons of
the phosphonate group observed in the NOESY map were vital for
the signal assignment and structure elucidation. Similar spectro-
scopic characteristics are displayed by the 3-diethylphosphonated
phlorin 3b and the 2-methylated derivative 3c, with obvious
differences related to the different substituent patterns.
NMR spectroscopy provides strong evidence for the non-
planarity of the macrocycle and its consequent chirality. It is
reflected in the first instance by the number of alkoxyl signals of the
phosphoryl group. The faces of the macrocycle are nonequivalent,
and thus, the methoxy signals are differentiated in the spectra of 3a
and 3c, while for the diethoxyphosphonated derivative 3b the
methylene signals of two magnetically inequivalent ethoxy groups
are diastereotopic. These spectral features unequivocally indicate
chirality of the phlorin systems.
Figure 1. UV−vis spectra of phlorin 3b (black solid line) and porphyrin
4b (blue solid line), and starting porphyrin 1a (red dotted line) in
dichloromethane.
696 nm, resembles those observed for N-confused phlorins,36
S-confused phlorin,49 or regular phlorins50−52 and considerably
differs from the spectrum of the starting NCP.
The 1H NMR spectrum of 3a is shown in Figure 2A along with
the partial signal assignments. The 1H NMR spectrum of 3a in
CDCl3 is characterized by six β-pyrrole proton signals in the
region of 6.55−6.96 ppm; thus, they are all shifted upfield with
respect to those in the spectrum of NCP (1a) in the same solvent.
The inner 21-CH signal of the confused pyrrole appearing in the
spectrum of 1a at about −5 ppm is remarkably shifted downfield to
δH 5.37 ppm in the spectrum of 3a. In the spectrum of 3a this signal
appears as a doublet of doublets due to scalar couplings with (a)
2-NH resonating at δH 9.05 ppm (4JHH = 2.4 Hz) and (b) the
phosphorus bound in the position 3 (4JHP = 4.4 Hz). The inner
22,24-NH proton signals of porphyrin 1a resonate around δH −2.5
ppm at low temperatures, whereas in the phlorin 3a appear in a
region of 8.2−8.8 ppm. The assignment of the NH signals was
confirmed by deuterium exchange experiments with D2O. Three
singlets at δH 2.22, 2.41, and 2.43 ppm are assigned to four methyls
of meso p-tolyl substituents. Two doublets at δH 3.38 and 3.81 ppm
The single-crystal X-ray diffraction analysis performed for 3b
confirms that the structural features derived from the solution
studies are also present in the solid state (Figure 3). Locations of
the phosphoryl group on C3 and the pyramidal carbon in the
meso-position 5 are apparent. The nonconfused pyrrole moieties
are essentially planar, and their structures are similar to those
observed in regular phlorins.51 Except for the C5 center, each of
the meso bridges is nearly coplanar with two adjacent pyrrole
rings. Nitrogen-bound hydrogens were identified in the difference
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1
Figure 2. H NMR spectrum (500 MHz, CDCl3) of 3a at 300 K (A), low-field part of the spectrum of 3a recorded at 235 K with a partial signal
assignment (A′), and 1H NMR spectrum (500 MHz, 300 K, CDCl3) of 4a (B). Expansions of indicated signals are shown in the insets.
density map at positions N2, N22, and N24. Due to the presence of a
stereogenic center at C5, the molecule is chiral. Nevertheless,
compound 3b crystallizes as a racemic phase in the centrosymmetric
that recorded for the faster-migrating enantiomer 1 allowing the
assignment of its configuration as R.
The reaction path leading from NCP to the phosphorylated
phlorin 3 (Scheme 2) involves activation of the porphyrin by an
acid, a step that was observed previously in several instances of
the reaction occurring at C3.24,25 In the case of NCP (1a), the
most likely activation process is protonation of the N2 position,
whereas for 1b, a similarly activated form can be obtained by
internal protonation of the macrocycle. Apparently, that
additional NH, once attached, stays with the macrocycle until
formation of the final phlorin 3 is completed, and unlike in the cases
of previously reported acid-catalyzed reactions,24,25 it is not
efficiently abstracted by atmospheric oxygen even when no effort
has been made to eliminate autoxidation. Instead of dehydrogen-
ation, an H-shift from C3 to C5 is operative upon attachment of the
phosphorus nucleophile. The acetate anion takes an important part
in the reaction mechanism as a dealkylating agent, converting the
cationic tris(alkoxy) moiety into a neutral dialkoxyposphoryl group.
̄
P1 space group, and thus the crystallographic unit cell consists of a
pair of symmetry-related enantiomers. Analysis of the nonbonding
distances in the crystal lattice reveals the occurrence of
intermolecular CH/π H-bonds53 between the unique p-tolyl
substituent at C5 and the π-conjugated system of the neighboring
molecule, mainly the pyrrole subunit comprising the N22 atom and
the confused pyrrole (Figure 4). Owing to that interaction, the crystal
lattice is organized into homochiral columns for both enantiomers.
Separation of the enantiomers of 3b was achieved by means of
HPLC on the chiral stationary phase. It resulted in an enantio-
merically pure fraction containing the faster migrating enantiomer,
while in the second fraction, the enantiomeric excess of the slower
migrating isomer was 90% because of a partial overlap of the
chromatographic bands (Figures 5A−C). The circular dichroism
spectra of these fractions are almost perfect mirror images to each
other, and both reveal two Cotton effects of opposite signs at the
wavelengths of the major bands of the optical spectrum of 3b
(Figure 5). The CD spectrum reflects the intrinsic chirality of the
phlorin ring, whose optical activity is extended on the whole
chromophore. To the best of our knowledge, this is the first example
of an optically active phlorin. To correlate the chirooptical response
of the enantiomers with their absolute configuration we calculated
the electronic transitions for the R enantiomer of phlorin 3b by
means of the time-dependent density functional theory (TD-DFT).
The calculated CD spectrum pattern is in very good agreement with
1
That was verified by means of the H NMR-monitored reaction
carried out for the 1a/P(OEt)3/AcOH system in C6D6 where
formation of the equivalent amount of ethyl acetate was observed
concurrently with the formation of 3b.
Although the phlorins 3 are relatively stable toward autoxidation
and their solutions can be handled in the presence of daylight and air,
they are slowly converted into other products by atmospheric
oxygen. One of these products can be efficiently obtained by the
reaction of 3 with a strong oxidant, e.g., 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ), followed by chromatographic workup
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Figure 3. Perspective view and atom numbering of the molecular
structure of 3b (R enantiomer, top). The cocrystallized chloroform
solvent molecule is omitted. In the bottom, the side views of both
enantiomers are presented. All hydrogen atoms and aryl substituents
except for that at C5 are omitted for clarity.
Figure 4. Lower box: Partial packing diagram for the crystal structure of
3b (30% probability ellipsoids) showing interatomic contacts between
overlapping parts of neighboring molecules. The nonbonding distances
(in Å) between non-hydrogen atoms and hydrogens at C57 (placed in
the idealized positions) are presented as green numbers. Upper box: A
space-filling representation of a fragment of the crystal lattice of 3b
showing spatial arrangement of enantiomeric columns. The green arrow
indicates a site of C57. Solvent molecules, ethyl substituents, and aryls in
the positions 10, 15, and 20 are omitted for clarity.
(Scheme 3). The product 4 was identified as 3-(dialkoxyphosphoryl)-
N-confused porphyrin, and it is apparently formed by dehydrogen-
ation of the positions 2 and 5 of the phlorin 3. Such reactivity is rare
among isolable phlorins49 because they usually comprise a
tetrahedral carbon with two non-hydrogen substituents in the
meso-position and their conversion into an aromatic macrocycle
such as porphyrin or chlorin is prevented.
The structures of the 3-phosphorylated NCP’s were confirmed
by high-resolution mass spectrometry, UV−vis, and multinuclear
NMR. In the ESI-MS spectra the molecular ion peaks at m/z
779.3145 (calcd 779.3146 for [M + H]+) for 4a and at 807.3444
(calcd 807.3459 for [M + H]+) for 4b indicate abstraction of two
hydrogen atoms from 3a or 3b, respectively. The UV−vis spectra
of 4a or 4b are characterized by six major bands at 290, 395, 452,
554, 600, and 770 nm. Their spectral pattern resembles that of the
starting porphyrin 1a, although all these bands are significantly red-
shifted in 4; the Soret band is shifted by 11 nm, and for the
Q-band appearing at the longest wavelength the red shift is about 40
nm (Figure 1). The 1H NMR spectra indicate an aromatic character
of the macrocycles consisting of 21-CH signal at
δH −4.33 ppm (4JHP = 2.3 Hz), a broad signal of the inner NHs
at δ −1.5 ppm, and signals of the β-pyrrole protons in the region of
8.3−8.9 ppm. A doublet at δH 3.52 ppm (3JHP = 11.0 Hz) in the
spectrum of 4a is that of the methoxy protons of the dimethyl-
phosphonate group, which are magnetically equivalent, unlike in
the case of the nonplanar phlorin 3a. Likewise, the methyl
protons of the ethoxy groups in the spectrum of 4b give rise to a
single triplet at δH 1.00 ppm. The methylene protons of the
ethoxy groups are diastereotopic, and two multiplets appear at δH
3.84 and 3.94 ppm. 1H−31P HMBC experiments reveal that 21-
CH as well as methylene and methyl protons of the substituents at
the phosphoryl fragment are scalar coupled to the phosphorus
resonating at δP 11.6 ppm.
To check whether the phosphoryl group at the position 3 can
alter the properties of the NCP coordination core we attempted
the insertion of nickel(II), zinc, and cadmium into 4 (Scheme 4).
In the case of nickel(II), the spectroscopic characteristics
indicate the formation of a square planar, diamagnetic species
1
(4−Ni) whose H NMR spectral pattern differs from that of
the unsubstituted NCP−nickel(II) complex by the absence of the 3-
CH signal and the presence of the ethoxyl signals (300 K, CD2Cl2).2
Methyl and methylene protons each give one signal at δH 1.19 and
3.87 ppm, respectively indicating magnetic equivalency of both
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(955.2110 calcd for [M + H]+), which indicates the presence of a
chloride ligand. Spectral characteristics of both complexes are
indicative of the coordination mode typical for adducts of the
Group 12 metals with NCP acting as a monoanion. Those
include proton signals of 2-NH (δH 9.08 ppm for 4−Zn and
9.38 ppm for 4−Cd) and 21-CH (δH 1.24 ppm for 4−Zn and
1.24 ppm for 4−Cd) appearing in the low- and high-field parts of
1
their H NMR spectra, respectively, and lack of the “internal”
NH’s. These protons are scalar coupled to each other as it can be
inferred from the COSY experiments. The position of the 21-CH
for 4−Zn is considerably shifted downfield (Δδ = 2−5 ppm)
with respect to those observed in the spectra of monomeric54 or
dimeric54,55 zinc complexes of NCP, which may be attributed to
the presence of the electron-withdrawing dialkylphosphoryl
substituent in position 3 of the confused pyrrole. A scalar
interaction of 21-CH with the 31P nucleus resonating at δP 8.9
and 5.4 ppm in the case of 4−Zn and 4−Cd, respectively, can be
1
deduced from the H−31P HMBC spectra for both complexes.
4
These interactions yield JHP coupling constants of 4.1 Hz for
4−Zn and 3.9 for 4−Zn. The scalar coupling to 31P is also observed
in the 13C NMR spectra for the C21 resonance (δC 72.5 ppm,
3JCP = 11.5 Hz for 4−Zn; δC 69.6 ppm, 3JCP = 10.5 Hz for 4−Cd).
The doublet corresponding to the C3 center, which is directly
bound to the phosphorus atom can be identified on the basis of
1H−13C HMBC experiment at δC 107.1 ppm (1JCP = 218 Hz) and
at δC 110.0 ppm (1JCP = 204 Hz) for the zinc and cadmium
derivatives, respectively. In each of the complexes, the macro-
cycle is nonplanar and its two faces are nonequivalent.
Consequently, the molecules of 4−Zn and 4−Cd are chiral,
which results in differentiation of H and 13C signals of alkyls
Figure 5. Top: Chiral-phase HPLC profiles (0.5 mg of solute, eluent
dichloromethane, flow 1 mL/min, detection at λ = 520 nm) of the
racemic 3b (A) and separated fractions 1 (B) and 2 (C). Bottom: UV−
vis and CD spectra of the separated fractions (dichloromethane
solutions). The gray bars represent electronic transitions calculated for
the R enantiomer (PCM-TD-B3LYP/6-311G**//6-31G**). The
spectra calculated for the enantiomer R are traced as green dashed lines.
1
attached to the phosphoryl group. Thus, there are two doublets
1
of phosphonate methyls in the H NMR spectrum of 4−Zn at
δH = 3.11 ppm (3JHP = 12.0 Hz) and 3.35 ppm (3JHP = 11.5 Hz)
and at δC = 53.0 ppm (2JCP = 6.1 Hz) and 54.2 ppm (2JCP = 4.2 Hz)
in the 13C NMR spectrum of this complex. In addition, methyls
of the ethoxy-subsituents in 4−Cd are magnetically inequivalent,
giving two triplets, while the two diasterotopic methylene
ethoxyls and, consequently, an effective planarity of the system. The
methylene signal is split into doublet of quartets with 2JHP = 7.8 Hz
and 3JHH = 7.1 Hz. Otherwise, the spectral features are indicative of
the coordination mode typical of NCP−nickel(II) complexes,2 and
those include the presence of a proton on the outer nitrogen N2
resonating at δH 10.61 ppm and a lack of any protons inside
the macrocyclic core as well as reduction of the aromaticity with
respect to that of the free base. Ethoxyl protons (both methylenes
1
fragments appear in the H NMR as four multiplets and in
13C NMR spectrum give two doublets at δC = 62.8 ppm (2JCP
=
5.3 Hz) and 64.0 ppm (2JCP = 4.0 Hz). In the case of 4−Cd, a
spin−spin coupling with 111,113Cd allows observation of “cadmium
satellites” associated with signals of certain protons in the 1H NMR
spectrum (Figure 7). For all β-pyrrole protons, the coupling constants
4JHCd ∼ 3.6−4.9 Hz confirm the coordination of the “regular” part of
the porphyrin,56 while in the case of 21-CH, the observed value of
1
and methyls) and 2-NH correlate in the H−31P HMBC with
J
HCd is 11 Hz. This value is close to that reported for dimeric cadmium
phosphorus resonating at δP 6.9 ppm. The presence of the nickel ion
can be derived from the HRMS (ESI-TOF) giving a molecular ion
peak at 863.2656 (calcd 863.2656 for [M + H]+). In the UV−vis
absorption spectrum of 4−Ni (Figure 6), the Soret region (250−
450 nm) resembles those of the unsubstituted or 2-alkylated NCP
nickel(II) complexes.2 However, Q-bands appearing at the longest
wavelengths are considerably red-shifted (50−80 nm) in 4−Ni.
Zinc(II) and cadmium(II) derivatives of 4 were obtained
under very mild conditions by stirring the ligand with an excess of
the corresponding anhydrous metal chloride in dichloromethane
(Scheme 4) followed by separation of the complex from the
inorganic salt by washing with water (in the case of 4−Zn) or
filtration and crystallization (4−Cd). ESI mass spectra confirm
coordination of metals by the presence of fragmentation peaks at
m/z 841.2272 (841.2281 calcd [M − Cl]+ for 4−Zn) and at m/z
919.2361 (919.2350 calcd [M − Cl]+ for 4−Cd) and, in the case
of 4−Cd, also by molecular ion peak at m/z = 955.2100
complexes of NCP (12 Hz)55 but it is considerably higher than that
observed for other systems consisting of side-on η1 or η2 coordinated
aromatic CH such as cadmium complexes of benziporphyrins (7.5 Hz
for m- and 4.4 Hz for p-benziporphyrin).57,58
Single-crystal X-ray diffraction analysis of 4−Cd (Figure 8)
unequivocally confirmed the structure of the complex, indicating
the presence of cadmium inside the macrocycle, coordination of
the “internal” nitrogens (distances Cd1−N(22−24): 2.267(4),
2.221(4), 2.258(4) Å), and an apical chloride (distance Cd1−Cl1
2.3995(16) Å) as well as a weak interaction of a side-on π-
bonding type between metal and C21 (distance Cd1−C21
2.579(5) Å). All these distances are shorter than those reported
for the analogous complex of S-confused porphyrin.49 The confused
pyrrole is considerably tipped out of the mean porphyrin plane P21
defined by 21 heavy atoms of the macrocyclic ring (i.e., all except for
N2, C3, and C21). A dihedral angle between the mean plane of the
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Scheme 2. Proposed Mechanism of the Formation of 3-Phosphorylated Phlorins
Scheme 3. Synthesis of 3-Phosphorylated NCP
Scheme 4. Insertion of Metal Ions into 4
confused pyrrole and P21 is 52.5°. The distances of Cd, C21, N2, and
C3 atoms from the mean plane are +0.95, −0.26, +1.44, and
+1.43 Å, respectively. The mean displacement of the atoms defining
P21 is 0.21 Å. The β-pyrrole carbons C7, C8, C17, and C18 lie 0.43−
0.5 Å under the plane, while C12, C13 lie about 0.3 Å over P21.
Because of the nonplanarity, the molecule is chiral, but as it was in
the case of crystals of 3b, crystallization in a centrosymmetric space
group C2/c indicates racemic character of the 4−Cd crystal phase.
The crystal unit cell consists of four pairs of the symmetry-related
enantiomers. Within the unit cell the crystal network is organized by
many weak interactions of a CH/π H-bond character,53 but the
strongest intermolecular interaction appears to be a double N−
H···OP hydrogen bond involving N2 and O1 of two molecules
related by an inversion center (Figure 8). Thus, effectively the crystal
lattice is constituted by the heterochiral dimeric assemblies where
intermolecular H-bonds (A···H 1.68 Å, D−A 2.694(5) Å, D−H···A
164.0°). In the case of the zinc complexes of regular 3-dialkyl-
phosphorylporphyrin, formation of dimers was also observed,42
although they consisted of homochiral subunits linked by
coordination of phosphoryl oxygens to the metal centers. On the
other hand, likely due to an unfavorable orientation of the PO
moiety, no intermolecular interactions involving the phosphoryl
group are observed in the crystal structure of phlorin 3b, despite the
presence of the hydrogen on N2 that could potentially form an
analogous H-bond bridge to that observed in the crystal of 4−Cd.
the enantiomers are held together by forming a ring N2−H2···O1′−
P1′−C3′−N2′−H2′···O1−P1− C3 comprising two relatively short
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Figure 6. Optical spectra of 4−Ni (black), 4−Zn (red), and 4−Cd
(green) in dichloromethane.
Separation of the enantiomers of 4−Cd was achieved by
HPLC performed on a chiral stationary phase with dichloro-
methane/ethyl acetate as the mobile phase. Despite the expected
lability that could result in demetalation on the chromatographic
column, the complex turned out to be stable. As it was for the
phlorin 3a, in the case of 4−Cd the bands consisting of
enantiomers overlapped, and thus separation of the slower
migrating stereoisomer was incomplete, though the faster band
contained pure enantiomer 1 (Figure 9). The optical activity of
the fraction was confirmed by the CD spectra showing the most
intense Cotton effect near 470 nm, that is at the wavelength of
the Soret band in the UV−vis spectrum of 4−Cd (Figure 9).
The absolute configuration of stereoisomers of 4−Cd was
assigned on the basis of a theoretically predicted CD spectrum of
the S enantiomer. The sign of the Cotton effect at 470 nm
observed for the slower migrating enantiomer 2 is the same as
that of the calculated CD spectrum; thus, configuration S can be
assigned to this stereoisomer. An analogous relation between the
absolute configuration and CD response has been observed
Figure 8. Top: Molecular structure and atom numbering of 4−Cd (the
S enantiomer is shown). Bottom: a pair of enantiomers interacting by
two hydrogen bonds. The para-tolyl substituents in the meso positions
of both molecules are omitted for clarity.
Figure 7. 1H NMR spectrum (600 MHz, CDCl3, 300 K) of 4−Cd. The inset on the left consists of extension of two β-pyrrole signals showing a satellite
pattern of scalar coupling with 111,113Cd. The inset on the right presents extension of the region where the signal of 21-CH occurs but which is partially
obscured by the signal of one of the methyls at 300 K (lower trace) and can be easily observed at 213 K (higher trace).
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CONCLUSION
■
We have shown that position 3 of NCP can be activated by a
weak acid toward reaction with phosphorus-containing nucleo-
philes under very mild conditions. The reaction of NCP with
trialkylphosphites is regiospecific as the substitution by
dialkylphosphoryl occurred solely at position 3 but also because
the hydrogen is attached in only one site, i.e., meso-position 5.
The formed phlorins 3 are chiral and relatively stable but can be
easily converted to the appropriate achiral porphyrins. Thus, the
reaction with phosphites is also a facile method of phosphor-
ylation of NCP. The phosphonate-bearing phlorins or
porphyrins as well as their metal complexes can interact with
other molecules by means of the −PO(OR)2 group and/or
macrocyclic core and thus can form supramolecular complexes
and that ability can be potentially applied in chiral recognition.
Relations between absolute configurations and CD response
established for 3 and 4−Cd can be also useful in the analysis of
stereocontrolled processes of coordination or supramolecular
assembling of other structurally related systems. This will be the
subject of our further study.
EXPERIMENTAL SECTION
■
General Methods. All of the reagents from commercial suppliers
were used without further purification. All of the solvents were freshly
distilled from the appropriate drying agents before use. The analytical
TLC was performed with silica gel 60 F254 plates. Column chroma-
tography was carried out by using silica gel 60 (200−300 mesh). The
NMR spectra were recorded on a spectrometer operating at 500 or
600 MHz for 1H, 125.6 or 150 MHz for 13C, and 202.4 or 243 MHz for
31P. TMS was used as an internal reference for 1H and 13C chemical shifts
Figure 9. Top: Chiral-phase HPLC profiles (0.5 mg of solute, eluent
dichloromethane/ethyl acetate 50/50, flow 2 mL/min, detection at λ =
520 nm) of the racemic 4−Cd (A) and separated fractions 1 (B) and 2
(C). Bottom: CD spectra of the separated fractions (dichloromethane
solutions). The gray bars represent electronic transitions calculated for
the enantiomer S and the calculated CD spectrum for this enantiomer is
drawn as a green dashed line.
and CDCl3 was the solvent. 31P signals were measured in presence of an
inset containing 85% H3PO4 as the external reference. Mass spectra were
recorded using matrix-assisted laser desorption ionization-time-of-flight
(MALDI-TOF) or electrospray ionization-time-of-flight (ESI-TOF)
methods and calibrated by means of internal standards. 2D experiments
were performed using standard pulse sequences. The low-temperature
NOESY spectra were recorded with 2048 × 512 data blocks and with a
400 ms mixing time. Resolution of stereoisomers was performed at room
temperature on a Chirex 3010 analytical column (25 cm length, 4.6 mm
i.d.) packed with 5 μm silica gel coated with covalently bound (S)-valine
and dinitroaniline. The HPLC-grade solvents were applied.
Calculations. Density functional theory (DFT and TD-DFT)
calculations were performed using Gaussian 09.60 DFT geometry
optimizations were carried out in unconstrained C1 symmetry, using
refined X-ray coordinates as starting geometries. DFT geometries were
refined to meet standard convergence criteria, and the existence of a
local minimum was verified by a normal-mode frequency calculation.
DFT calculations were performed using the hybrid functional
B3LYP,61−63 combined with the 6-31G(d,p) and LANL2DZ64−66
basis sets (3b and 4−Cd, respectively). The electronic and CD spectra
were simulated by means of time-dependent density functional theory
(TD-DFT). In each case 15 states were calculated. For these calculations,
the polarizable continuum model of solvation was used (PCM,
dichloromethane), and, in the case of 4−Cd, the basis set was expanded
to 6-311G(d,p). The electronic transitions, UV/vis, and CD spectra were
analyzed by means of the GaussSum program.67 The transitions were
convoluted by Gaussian curves with 2000 cm−1 and 0.25 eV half line widths
for the UV/vis and CD spectra, respectively.
recently for other derivatives comprising a chirality plane, such as
21-alkylated or 21-alkoxylated NCP.48 Our attempt to crystallize
the separated enantiomers for both fractions resulted in racemic
phases which were isostructural with that already obtained when
started from the racemic 4−Cd. For both enantiomers about
50% decay of the Cotton effect intensities was observed in the
CD spectra after 20 h at room temperature, while the UV−vis
spectra remained unaltered. These observations indicate slow
racemization of 4−Cd, which is possible due to a labile character
of this type of complexes,59 allowing configuration changes that
may result in racemization or enantiomerization in the presence
of a chiral anionic ligand.
Dimerization of 4−Cd in the solid state prompted us to analyze
whether an analogous dimer could also be detected in solution.
However, in the 1H NMR spectra we did not observe any features
indicative for the closeness of the porphyrin molecules, such as up/
downfiled shift of certain signals or spectral pattern alteration upon
up to 80-fold dilution (10.0−0.12 mM) of the 4−Cd complex
solutions in C6D6 or in CDCl3. It may indicate monomeric rather
than dimeric character of the complex in solution since upon the
concentration change a monomer/dimer equilibrium would cause
changes in the chemical shifts of the signals of some protons
localized in the vicinity of the bridging moieties.24 As the dimeric
assembly in the solid state consists of heterochiral units, one can
expect differences in the spectral properties of the separated
enantiomers and the racemic mixture if such a dimer would exist in
Syntheses of Precursors. Starting porphyrins 1a and 1b were
synthesized as previously described.68,69
3-(Dialkoxyphosphoryl)-5H-5,10.15.20-tetrakis(p-tolyl)-2-
aza-21-carbaphlorins 3. In a typical synthesis of 3, a solution
containing 67 mg (0.1 mmol) of NCP (1) and 60 mg (0.5 mmol) of
trimethyl phosphite or 80 mg (0.5 mmol) of triethylphosphite and 30 mg
(0.5 mmol) of acetic acid in 25 mL of anhydrous and deareated benzene
was stirred and heated to reflux for 1.5 h under nitrogen. After that time,
TLC showed no NCP reactant left. The solvent was then evaporated, and
1
the solution. Apparently, both H NMR and optical spectra of
enantiomerically pure and racemic solutions are identical
indicating the lack of that kind of dimerization.
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the residue was chromatographed on a silica gel column with
dichloromethane/methanol mixture (v/v = 100:3) as an eluent. The
blue-green colored product fractions were combined together, followed
by removal of solvent to afford derivative 3 as a blue powder. Yields: 62 mg
(79%) for 3a, 57 mg (70%) for 3b, 57 mg (70%) for 3c.
separated by the silica gel column with a dichloromethane/methanol
mixture (v/v = 100:5) as an eluent. The brown fraction contained 4,
which precipitated as a red-brown powder upon addition of hexane.
Yields: 25 mg (65%) for 4a, 24 mg (60%) for 4b.
Selected data for 4a: 1H NMR (500 MHz, CDCl3, 298 K) δH = −4.33
(d, 4JHP = 2.3 Hz, 1H, 21-CH), 2.67 (s, 3H, −CH3), 2.68 (s, 6H, −CH3),
2.69 (s, 3H, −CH3), 3.52 (d, 3JHP = 11.0 Hz 6H, −OCH3), 7.54 (t, J = 9.0
Hz, 4H, ArH), 7.61 (d, J = 7.5 Hz, 2H, ArH), 8.03 (d, J = 7.5 Hz, 2H,
ArH), 7.97 (d, J = 7.5 Hz, 2H, ArH), 8.02 (d, J = 7.5 Hz, 2H, ArH),
8.25−8.28 (m, 4H, ArH), 8.39−8.44 (m, 4H, pyrrH), 8.75 (d, J = 4.5 Hz,
1H, pyrrH), 8.87 (d, J = 4.5 Hz, 1H, pyrrH); 13C NMR (125 MHz,
CDCl3, 298 K) δC = 21.5, 21.56, 21.64, 53.3 (d, JCP = 6.8 Hz), 93.2,
116.7, 118.8, 125.2, 126.7, 126.8, 127.86, 127.93, 128.0, 128.8, 130.1,
131.4, 133.1, 133.4, 134.66, 134.72, 135.2, 136.7, 136.8, 137.5, 137.6,
138.3, 138.4, 138.5, 138.59, 138.64, 141.6, 142.7, 146.6, 146.9, 148.3,
157.3, 158.8; 31P NMR (202.4 MHz, CDCl3, H3PO4, 298 K) δP = 13.6;
UV−vis (CHCl3) λmax/nm (log ε) 395 (4.56), 452 (5.13), 554 (3.95),
601 (3.86), 773 (4.16); HRMS (ESI-TOF) m/z = 779.3145 (obsd),
779.3146 (calcd for C50H44N4O3P [M + H]+), ΔM/M = 0.1 ppm.
Selected data for 4b: 1H NMR (500 MHz, CDCl3, 298 K) δH = −4.40
Selected data for 3a: 1H NMR (500 MHz, CDCl3, 298 K) δH = 2.22
(s, 3H, −CH3), 2.41 (s, 6H, −CH3), 2.43 (s, 3H, −CH3), 3.78 (d, 3JHP
=
7.0 Hz, 3H, −OCH3), 3.81 (d, 3JHP = 7.0 Hz, 3H, −OCH3), 5.37 (dd,
4J = 2.5 Hz, 4JHP = 4.3 Hz 1H, 21-CH), 6.28 (s, 1H, 5-CH), 6.52 (d, J =
4.5 Hz, 1H, pyrrH), 6.57−6.59 (m, 2H, pyrrH), 6.73 (d, J = 5.5 Hz, 1H,
pyrrH), 6.84 (d, J = 4.5 Hz, 1H, pyrrH), 6.89 (d, J = 8.0 Hz, 1H, ArH),
6.92 (d, J = 5.5 Hz, 1H, pyrrH), 6.97 (d, J = 8.0 Hz, 2H, ArH), 7.19−7.22
(m, 8H, ArH), 7.30−7. 33(m, 3H, ArH), 8.32 (br, 1H, 24-NH), 8.79 (br,
1H, 22-NH), 8.85 (br, 1H, 2-NH); 1H NMR (500 MHz, CDCl3, 235 K)
δ 2.27 (s, 3H, −CH3), 2.45 (s, 6H, −CH3), 2.48 (s, 3H, −CH3), 3.31 (d,
J = 11.5 Hz, 3H, −OCH3), 3.93 (d, J = 11.5 Hz, 3H, -OCH3), 5.29
(s, 1H, 21-CH), 6.29 (s, 1H, 5-CH), 7.24−7.34 (m, 8H, ArH),7.38−
7.43 (m, 3H, ArH), 7.72 (d, J = 7.5 Hz, 1H, ArH), 8.24 (br, 1H, 24-NH),
8.75 (br, 1H, 22-NH), 9.06 (br, 1H, 2-NH);13C NMR (125 MHz,
CDCl3, 298 K) δC = 20.9, 21.3, 21.4, 41.7, 52.9 (d, JCP = 8.1 Hz), 53.1 (d,
JCP = 8.1 Hz), 104.9 (d, JPC = 14.3 Hz), 109.3, 112.5, 111.6, 112.7 (d, JCP
= 225.6 Hz), 122.8, 127.3, 127.7, 128.0, 128.3, 128.6, 129.0, 129.2, 129.6,
131.0 (d, JCP = 15.7 Hz), 131.2, 132.1, 133.6, 133.8, 134.9, 135.5, 136.18,
136.5, 137.0 (d, JCP = 12.4 Hz), 137.17, 137.19, 137.80, 137.84, 138.0,
139.5, 143.1, 146.1, 151.2, 166.5; 31P NMR (202.4 MHz, CDCl3,
H3PO4, 298 K) δP = 13.9; UV−vis (CHCl3) λmax/nm (log ε) 415 (3.75),
643 (3.27), 696 (3.46); HRMS (ESI-TOF) 781.3305 (obsd), 781.3302
(calcd for C50H46N4O3P [M + H]+), ΔM/M = −0.4 ppm.
4
(d, JHP = 2.3 Hz, 1H, 21-CH), 1.01 (t, J = 7.0 Hz, 6H, −CH3), 2.65
(s, 3H, −CH3), 2.66 (s, 3H, −CH3), 2.67 (s, 6H, −CH3), 3.84 (m, 2H,
−OCH2−), 3.94 (m, 2H, −OCH2−), 7.52 (d, J = 7.5 Hz, 2H, ArH), 7.53
(d, J = 7.4 Hz, 2H, ArH), 7.58 (d, J = 7.9 Hz, 2H, ArH), 7.64 (d, J = 7.7
Hz, 2H, ArH), 7.97 (d, J = 7.9 Hz, 2H, ArH), 8.01 (d, J = 7.4 Hz, 2H,
ArH), 8.23 (d, J = 7.4 Hz, 2H, ArH), 8.25 (d, J = 7.6 Hz, 2H, ArH), 8.38
(d, J = 5.0 Hz, 1H, pyrrH), 8.41 (d, J = 4.8 Hz, 1H, pyrrH), 8.43 (d, J =
4.6 Hz, 1H, pyrrH), 8.44 (d, J = 4.6 Hz, 1H, pyrrH), 8.73 (d, J = 4.9 Hz,
1H, pyrrH), 8.89 (d, J = 4.9 Hz, 1H, pyrrH); 13C NMR (125 MHz,
CDCl3, 298 K) δC = 21.49, 21.51, 21.65, 62.7 (d, JCP = 6.5 Hz), 94.1,
116.7, 118.6, 125.2, 126.7, 126.8, 127.8, 127.9, 128.6, 130.0, 131.2, 133.3,
133.5, 134.6, 134.7, 135.1, 136.7, 136.9, 137.5, 137.6, 137.7, 138.1, 138.2,
138.49, 138.52, 138.6, 138.7, 141.4, 142.4, 146.7, 147.0, 157.2, 158.5; 31P
NMR (202.4 MHz, CDCl3, H3PO4, 298 K) δP = 11.7. UV−vis (CH2Cl2)
λmax/nm (log ε) 261 (4.32), 291 (4.37), 394 (sh), 451 (5.25), 516
(sh), 551 (4.03), 599 (3.89), 707 (3.74), 771 (4.20); HRMS ESI-TOF)
m/z = 807.3444 (obsd), 807.3459 (calcd for C52H48N4O3P [M + H]+),
ΔM/M = 1.8 ppm.
Selected data for 3b: 1H NMR (500 MHz, CDCl3, 298K) δH = 1.09
(t, J = 7.5 Hz, 3H, −CH3), 1.38 (t, J = 7.5 Hz, 3H, −CH3), 2.24 (s, 3H,
−CH3), 2.43 (s, 6H, −CH3), 2.45 (s, 3H, −CH3), 3.58−3.63 (m, 1H,
−OCH2), 3.86−3.90 (m, 1H, −OCH2), 4.14−4.19 (m, 1H, −OCH2),
4.22−4.27 (m, 1H, −OCH2), 5.43 (dd, 4J = 2.6 Hz, 4JHP = 4.5 Hz 1H, 21-
CH), 6.36 (s, 1H, 5-CH), 6.53 (d, J = 4.5 Hz, 1H, pyrrH), 6.59 (d, J = 3.5
Hz, 1H, pyrrH), 6.61 (d, J = 3.5 Hz, 1H, pyrrH), 6.73 (d, J = 5.5 Hz, 1H,
pyrrH), 6.85 (d, J = 4.5 Hz, 1H, pyrrH), 7.21−7.24 (m, 7H, ArH), 7.32−
7.35(m, 4H, ArH), 8.37 (br, 1H, 24-NH), 8.89 (br, 1H, 22-NH), 8.92
(br, 1H, 2-NH); 13C NMR (125 MHz, CDCl3, 298 K) δC = 15.98, 16.04,
16.38, 16.44, 20.9, 21.27, 21.35 41.7, 62.5 (d, JCP = 8.1 Hz), 62.6 (d, JCP
=
(3-(Diethoxyphosphoryl)-5,10.15.20-tetrakis(p-tolyl)-2-aza-
21-carbaporphyrinato)nickel(II) (4−Ni). To a deareated solution of
4b (20 mg, 0.024 mmol) in dichloromethane (10 mL) was added a
solution of nickel diacetate tetrahydrate (30 mg, 0.12 mmol) in ethanol
(5 mL), and the mixture was heated under reflux for 2 h in the
atmosphere of nitrogen. The solvent was then removed, and the solid
residue was dissolved in dichloromethane and passed down a short silica
gel column with dichloromethane as an eluent. The fastest moving green
band was collected, solvent was partially evaporated, and compound 4−
Ni was precipitated by addition of hexane. The olive powder was
collected by filtration. Yield: 12 mg (55%).
8.1 Hz), 105.1 (d, JCP = 13.6 Hz), 108.2, 109.2, 111.5, 111.7, 114.4 (d,
JCP = 224.3 Hz), 122.8, 127.3, 127.6, 127.9, 128.2, 128.5, 128.9, 129.0,
129.6, 130.3 (d, JCP = 16.3 Hz), 131.2, 132.1, 133.5, 133.7, 135.0, 135.4,
136.1, 136.5, 136.6 (d, JCP = 11.7 Hz), 137.2, 137.8, 137.9, 138.0, 139.7,
143.0, 146.1, 151.1, 166.5; 31P NMR (202.4 MHz, chloroform-d,
H3PO4, 298 K) δP = 10.9; UV−vis (CHCl3) λmax/nm (log ε) 417 (3.73),
649 (3.25), 698 (3.44); HRMS (ESI-TOF) 809.3618 (obsd), 809.3615
(calcd for C52H50N4O3P [M + H]+), ΔM/M = −0.4 ppm.
Selected data for 3c: 1H NMR (500 MHz, CDCl3, 298 K) δH = 2.24
(s, 3H, −CH3), 2.41 (s, 3H, −CH3), 2.43 (s, 3H, −CH3), 2.45 (s, 3H,
−CH3), 3.13 (s, 3H, NCH3), 3.38 (d, JHP = 11.5 Hz, 3H, −OCH3), 3.67
(d, JHP = 11.5 Hz, 3H, −OCH3), 5.05 (d, JHP = 4.5 Hz, 1H, 21-CH), 6.50
(d, J = 4.5 Hz, 1H, pyrrH), 6.61 (d, J = 3.0 Hz, 1H, pyrrH), 6.67 (d, J =
3.0 Hz, 1H, pyrrH), 6.78 (d, J = 5.0 Hz, 1H, pyrrH), 6.85 (d, J = 4.5 Hz,
1H, pyrrH), 6.93 (d, J = 9.0 Hz, 3H, ArH+5-CH), 6.99 (d, J = 8.0 Hz,
2H, ArH), 7.21−7.24 (m, 10H, ArH), 7.32 (d, J = 7.0 Hz, 2H, ArH), 7.63
(br, 1H, 24-NH), 8.07 (br, 1H, 22-NH), 8.82 (br, 1H, 2-NH); 13C NMR
Selected data for 4−Ni: mp >300 °C; 1H NMR (600 MHz, CD2Cl2,
300 K) δH = 1.19 (t, J = 7.1 Hz, 6H, −CH3), 2.51 (s, 6H, −CH33), 2.53
3
(s, 3H, −CH3), 2.55(s, 3H, −CH3), 3.86 (dq, JHP = 7.8 Hz, JHH
=
7.1 Hz, 4H, −OCH2−), 7.25 (d, J = 8.4 Hz, 2H, ArH), 7.34 (d, J = 8.4
Hz, 2H, ArH), 7.35 (d, 3JHH = 5.1 Hz, 1H, pyrrH), 7.36 (d, J = 8.5 Hz,
2H, ArH), 7.45 (d, 3JHH = 5.1 Hz, 1H, pyrrH), 7.47 (d, J = 7.8 Hz, 2H,
ArH), 7.51 (d, 3JHH = 5.1 Hz, 1H, pyrrH), 7.54 (d, J = 8.0 Hz, 2H, ArH),
7.55 (d, J = 8.0 Hz, 2H, ArH), 7.58 (d, J = 8.0 Hz, 2H, ArH), 7.61 (d,
3JHH = 4.8 Hz, 1H, pyrrH), 7.64 (d, 3JHH = 4.8 Hz, 1H, pyrrH), 7.69 (d,
J = 8.2 Hz, 2H, ArH), 7.76 (d, 3JHH = 5.1 Hz, 1H, pyrrH), 10.61 (br, 1H,
2-NH); 13C NMR (150 MHz, CD2Cl2, 300 K) δC = 15.4 (d, JCP = 6.8 Hz,
−CH3), 20.62, 20.63, 20.67, 20.71, 62.5 (d, JCP = 5.5 Hz, −OCH2−),
110.8, 116.9, 117.5, 119.3, 124.5, 126.0, 127.49, 127.54, 128.2, 129.0,
129.2, 131.9, 132.1, 132.2, 132.4, 132.5, 133.3, 134.3, 135.9, 136.8, 137.1,
137.2, 138.2, 145.5, 148.0, 150.0, 150.7, 154.6, 155.7, 156.7; 31P NMR
(243 MHz, CD2Cl2, H3PO4, 298 K) δP = 6.9; UV−vis (CH2Cl2) λmax/nm
(log ε) 366 (4.41), 431 (4.51), 462 (4.39), 525 (3.35), 566 (3.75), 627
(3.68), 783 (3.26), 871 (3.26); HRMS (ESI-TOF) m/z = 863.2656
(obsd), 863.2656 (calcd for C52H46N4O3PNi [M + H]+), ΔM/M =
0.0 ppm.
(125 MHz, CDCl3, 298 K) δC = 21.0, 21.3, 21.4, 34.7, 41.6, 52.3 (d, JCP
=
6.1 Hz), 52.5 (d, JCP = 6.1 Hz), 102.9 (d, JCP = 14.4 Hz), 109.4, 110.5,
112.1, 113.2 (d, JCP = 221.5 Hz), 123.3, 127.2, 127.8, 128.96, 127.98,
128.50, 128.8, 129.6, 130.0, 131.5, 132.1, 133.2, 133.8, 135.4, 135.8,
136.47, 136.55, 136.9, 137.0, 137.1, 137.21, 137.71, 137.79, 137.84,
139.6, 141.0, 144.6, 145.3, 150.7, 166.3; 31P NMR (202.4 MHz, CDCl3,
H3PO4, 298 K) δP = 13.9; UV−vis (CHCl3) λmax/nm (log ε) 418 (3.68),
633 (3.25), 685 (3.44); HRMS (ESI-TOF) m/z = 795.3455 (obsd),
795.3459 (calcd for C51H48N4O3P [M + H]+), ΔM/M = 0.5 ppm.
3-(Dialkoxyphosphoryl)-5,10.15.20-tetrakis(p-tolyl)-2-aza-
21-carbaporphyrins 4. In the typical preparation, to a dichloro-
methane solution of 3 (40 mg, 0.05 mmol) was added 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (30 mg, 14 mmol), and the mixture was
stirred for 5 min. After evaporation of the solvent, the components were
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(3-(Dimethoxyphosphoryl)-5,10,15,20-tetrakis(p-tolyl)-2-
aza-21-carbaporphyrinato)zinc Chloride (4−Zn). A mixture of 4a
(30 mg, 0.038 mg) and zinc(II) chloride (30 mg, 22 mmol) in CH2Cl2
(10 mL) was stirred at room temperature for 40 min. Then the reaction
mixture was washed three times with water. The organic layer was dried
with anhydrous Na2SO4, and the solvent was removed under reduced
pressure to give the crude product. The crude product was recrystallized
from a mixture of toluene/hexane to afford 4−Zn in 95% yield (32 mg).
Selected data for 4−Zn: 1H NMR (500 MHz, CDCl3, 298 K) δH =
1.24 (dd, 4J = 1.8 Hz, 4JHP = 4.0 Hz 1H, 21-CH), 2.53 (s, 6H, −CH3),
2.57 (s, 3H, −CH3), 2.58 (s, 3H, −CH3), 3.11 (d, J = 12.0 Hz, 3H,
-OCH3), 3.35 (d, J = 12.0 Hz, 3H, −OCH3), 7.34 (d, J = 9.0 Hz, 4H,
ArH), 7.43 (d, J = 7.5 Hz, 2H, ArH), 7.49−7.54 (m, 6H, ArH), 7.62 (br,
2H, ArH), 7.74 (d, J = 9.0 Hz, 2H, pyrrH), 7.81 (m, 2H, pyrrH), 7.96
(d, J = 5.0 Hz, 1H, pyrrH), 8.10 (d, J = 5.0 Hz, 1H, pyrrH), 9.08 (br, 1H,
2-NH); 1H NMR (500 MHz, CDCl3, 243 K) δH = 1.23 (dd, 4J = 2.1 Hz,
4JHP = 4.0 Hz 1H, 21-CH), 2.56 (s, 6H, −CH3), 2.60 (s, 6H, −CH3),
X-ray quality crystals of 3b were obtained by slow evaporation of
chloroform from the solution. Crystal data for 3b: C52H49N4O3P·
CHCl3, Mr = 928.29, T = 100(2) K, CuKα radiation, triclinic, space
̄
group P1, a = 9.708(3) Å, b = 15.036(2) Å, c = 16.375(4) Å, α = 91.37
(2)°, β = 97.32(2)°, γ = 91.43(2)°, V = 2368.3(9) Å3, Z = 2, Dc = 1.302
Mg m−3, λ = 1.54178 Å, μ = 2.449 mm−1, diffractometer with CCD
detector, 2.72 ≤ θ ≤ 59.00°, 15769 collected reflections, 6745
independent reflections, 590 parameters, R1(F) = 0.1156, wR2(F2) =
0.3018, S = 1.553, largest difference peak and hole 0.471 and −0.510
e·Å−3. The asymmetric unit consists of one molecule of 3b and one
molecule of chloroform. One of the ethyl substituents is disordered over
two equally occupied positions. The low quality of the crystal, which was
caused by partial loss of the cocrystallized chloroform solvent, was
responsible for the weak diffraction observed for θ > 59°, resulting in
relatively low precision of the crystal data and structural parameters.
Unfortunately, other attempts to grow X-ray quality crystals were not
successful.
X-ray quality crystals of 4−Cd were obtained by slow diffusion of the
benzene solution of 4−Cd into hexane at room temperature. Crystal
data for 4−Cd: C52H46CdClN4O3P, Mr = 953.75, T = 100(2) K, MoKα
radiation, monoclinic, space group C2/c, a = 28.913(1) Å, b =
11.6762(4) Å, c = 31.837 (2) Å, α = 90.00°, β = 104.692(4)°, γ = 90.00°,
V = 10396.7(8) Å3, Z = 8, Dc = 1.219 Mg m−3, λ = 0.71073 Å, μ = 0.544
mm−1, diffractometer with CCD detector, 2.74 ≤ θ ≤ 27.00°, 26730
collected reflections, 11195 independent reflections, 558 parameters,
R1(F) = 0.071, wR2(F2) = 0.1612, S = 1.063, largest difference peak and
hole 1.301 and −1.107 e·Å−3. One of the ethyl substituents is disordered
over two equally occupied positions.
3.12 (d, J = 11.5 Hz, 3H, −OCH3), 3.68 (d, J = 11.5 Hz, 3H, −OCH3),
7.34−7.41 (m, 4H, ArH), 7.47−7.55 (m, 8H, ArH + pyrrH), 7.56 (d, J =
5.0 Hz, 1H, pyrrH), 7.59 (d, J = 5.0 Hz, 1H, pyrrH), 7.75 (d, J = 7.5 Hz,
2H, ArH), 7.78 (d, J = 7.5 Hz, 2H, ArH),7.84 (d, J = 7.0 Hz, 2H, ArH),
8.01 (d, J = 5.0 Hz, 1H, pyrrH), 8.03 (d, J = 5.0 Hz, 1H, pyrrH), 9.16 (br,
1H, 2-NH); 13C NMR (125 MHz, CDCl3, 298 K) δC = 21.4, 21.5, 53.0
(d, JCP = 8.1 Hz), 54.1 (d, J = 8.1 Hz), 72.5 (d, JCP = 11.0 Hz), 107.1
(d, JCP = 215.3 Hz), 117.0, 117.39, 127.6, 128.0, 128.9, 129.3, 132.4,
133.1, 133.3, 133.8, 133.9, 134.0, 134.2, 134.5, 135.28, 135.35, 135.5,
137.1, 137.6, 137.7, 137.9, 138.9, 140.1, 153.1, 158.5, 159.1, 164.7,
165.5; 31P NMR (202.4 MHz, CDCl3, H3PO4, 298 K) δP = 8.9. UV−vis
(CHCl3) λmax/nm (log ε) 327 (4.44), 381 (4.32), 465 (5.02), 759
(4.01), 842 (4.41); HRMS (ESI-TOF) m/z = 841.2272 (obsd),
841.2281 (calcd for C50H42N4O3PZn [M − Cl]+), ΔM/M = 1.1 ppm.
(3-(Diethoxyphosphoryl)-5,10,15,20-tetrakis(p-tolyl)-2-aza-21-
carbaporphyrinato)cadmium Chloride (4−Cd). A mixture of 4b
(30 mg, 0.037 mg) and anhydrous cadmium chloride (30 mg, 16 mmol)
in CH2Cl2 (10 mL) was stirred at room temperature for 12 h. The
reaction mixture was then filtered on a sintered glass microfilter, solvent
was evaporated, the solid residue was dissolved in 5 mL of benzene, and
the solution was filtered by means of polystyrene microfilter. The
complex 4b formed dark green crystals upon addition of an equal
volume of hexane. Yield: 28 mg (80%).
ASSOCIATED CONTENT
■
S
* Supporting Information
Crystallographic data (CIF), calculation details (Table S1), Cartesian
coordinates for the optimized structures (Table S2 and S3),
calculated electronic transitions (Table S4 and S5), 1D and 2D
NMR, and mass spectra. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
1
Corresponding Author
*E-mail: lixiaofang@iccas.ac.cn, piotr.chmielewski@chem.uni.
wroc.pl.
Selected data for 4−Cd: mp >250 °C dec; H NMR (500 MHz,
CDCl3, 298 K) δH = 0.87 (t, J = 7.0 Hz, 3H, −CH3), 1.13 (t, J = 7.1 Hz,
3H, −CH3), 1.14 (m, 1H, 21-CH), 2.52 (s, 3H, −CH3), 2.52 (s, 3H,
−CH3), 2.55 (s, 3H, −CH3), 2.57 (s, 3H, −CH3), 3.45 (m, 1H,
−OCH2−), 3.63 (m, 2H, −OCH2−), 3.87 (m, 1H, −OCH2−), 7.33 (d,
J = 8.0 Hz, 3H, ArH), 7.39 (d + dd, 3JHH = 4.9 Hz, 4JHCd = 4.0 Hz, 1H,
Notes
The authors declare no competing financial interest.
pyrrH), 7.41 (d, J = 7.8 Hz, 2H, ArH), 7.45 (d + dd, 3JHH = 4.7 Hz, 4JHCd
=
3.6 Hz, 1H, pyrrH), 7.499 (d, 2H, J = 7.3, ArH), 7.503 (d + dd, 3JHH = 4.9
Hz, 4JHCd = 4.0 Hz, 1H, pyrrH), 7.53 (d + dd, 3JHH = 4.9 Hz, 4JHCd = 4.9 Hz,
1H, pyrrH), 7.60 (br, 2H, ArH), 7.72 (d, J = 7.7 Hz, 2H, ArH), 7.79 (d, J =
8.1 Hz, 2H, ArH), 7.87 (d + dd, 3JHH = 4.8 Hz, 4JHCd = 4.3 Hz, 1H, pyrrH),
7.90 (d + dd, 3JHH = 4.9 Hz, 4JHCd = 4.9 Hz, 1H, pyrrH), 9.32 (br, 1H, 2-
NH); 13C NMR (125 MHz, CDCl3, 298 K) δC = 15.9 (d, JCP = 7.0 Hz,
−CH3), 16.0 (d, JCP = 7.0 Hz, −CH3), 21.4, 21.5, 62.8 (d, JCP = 5.7 Hz, −
OCH2), 64.0 (d, JCP = 3.9 Hz, -OCH2), 69.8 (d, JCP = 12.5 Hz, C21), 110.2
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (Grant No. 20971041), the Key Project of
Chinese Ministry of Education (Grant No. 210146), the Open
Project Program of Key Laboratory of Theoretical Chemistry
and Molecular Simulation of Ministry of Education, Hunan
University of Science and Technology, and the Polish National
Science Center (Grant No. 2012/04A/ST5/00593). Quantum
chemical calculations were performed in the Wrocław Center for
Networking and Supercomputing.
(d, JCP = 211.5 Hz, C3), 118.1, 118.5, 127.8, 128.0, 129.5, 129.6 (d, JCP
=
13.2 Hz), 132.8, 133.3, 133.9, 134.2, 134.3, 134.4, 134.6, 134.7, 134.9, 135.0,
135.3, 135.5, 137.02, 137.05, 137.9, 138.1, 138.3, 138.9, 140.1, 153.5, 153.6,
160.3, 161.9, 165.0, 165.9; 31P NMR (243 MHz, CD2Cl2, H3PO4, 298 K)
δP = 5.4. UV−vis (CH2Cl2) λmax/nm (log ε) 216 (4.25), 328 (4.47), 3.89
(sh), 469 (4.99), 560 (sh), 611 (3.35), 676 (sh), 777 (sh), 859 (4.45);
HRMS (ESI-TOF) m/z = 919.2361 (obsd), 919.2350 (calcd for
C52H46N4O3PCd [M − Cl]+), ΔM/M = −1.2 ppm, 955.2100 (obsd),
955.2110 (calcd for C52H47N4O3PClCd [M + H]+), ΔM/M =1.0 ppm.
Crystallographic Data. The structures were solved by direct
methods using the SHELXS program.70 All non-hydrogen atoms were
refined anisotropically by full matrix least-squares with SHELXL-97.70
All H atoms, including those located in the difference density map, were
placed in calculated positions and refined as the riding model with
Uiso(H) = 1.2Ueq(C).
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