Meso-tetraphenylbenzoporphyrin-22,23-dicarboxylic anhydride: A platform to benzoporphyrin derivatives

Article abstract of DOI:10.1021/jo400948s

A method to synthesize meso-tetraphenylbenzoporphyrin-2²,2 ³-dicarboxylic anhydride is reported. This compound reacts with alkylamines and arylamines to afford the corresponding phthalimides in moderate to excellent yields. The reaction of the title compound with benzene-1,4-diamine or with benzene-1,3-diamine yields the corresponding N,N′-(phenylene)bisphthalimides, whereas with benzene-1,2-diamine or naphthalene-1,8-diamine it affords heterocyclic-fused porphyrins. Molecular mechanics simulations elucidates the multiplicity of signals observed in the NMR spectra of the N,N′-(1,4-phenylene)bisphthalimide 11. This molecule exhibits two preferential conformations corresponding to a coplanar and an almost perpendicular arrangement of the benzoporphyrin units relative to the central benzenic ring.

Full text of DOI:10.1021/jo400948s

Article
pubs.acs.org/joc
meso‑Tetraphenylbenzoporphyrin‑22,23‑dicarboxylic Anhydride: A
Platform to Benzoporphyrin Derivatives
Carla M. B. Carvalho,† Sergio M. Santos,‡ Maria G. P. M. S. Neves,*,† Augusto C. Tome,*,†
́
́
Artur M. S. Silva,† Joao Rocha,‡ and Jose A. S. Cavaleiro†
́
̃
†Department of Chemistry, QOPNA and Department of Chemistry, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal
‡
S
* Supporting Information
ABSTRACT: A method to synthesize meso-tetraphenylbenzoporphyrin-22,23-dicarboxylic anhydride is reported. This
compound reacts with alkylamines and arylamines to afford the corresponding “phthalimides” in moderate to excellent yields.
The reaction of the title compound with benzene-1,4-diamine or with benzene-1,3-diamine yields the corresponding N,N′-
(phenylene)bisphthalimides, whereas with benzene-1,2-diamine or naphthalene-1,8-diamine it affords heterocyclic-fused
porphyrins. Molecular mechanics simulations elucidates the multiplicity of signals observed in the NMR spectra of the N,N′-
(1,4-phenylene)bisphthalimide 11. This molecule exhibits two preferential conformations corresponding to a coplanar and an
almost perpendicular arrangement of the benzoporphyrin units relative to the central benzenic ring.
diester 3 as the main product.20 We have also been interested
INTRODUCTION
■
in developing new synthetic routes to pyrrolo[3,4-b]-
Porphyrins with π-extended conjugation have received much
porphyrins21 and recently demonstrated that N-methylpyrrolo-
attention within the scientific community in recent years. Such
[3,4-b]porphyrin 1 acts as a diene in Diels−Alder reactions
type of compounds display improved photophysical and
with singlet oxygen, leading to the formation of the
electrochemical properties and are particularly useful for
corresponding 1,3-dioxopyrrolo[3,4-b]porphyrin.22 We now
applications in medicine and materials sciences.1−4 The
demonstrate that pyrroloporphyrin 1 may be converted, in
extension of the macrocyclic π-system through β,β′-fused
aromatic rings typically causes significant red-shifts in the
absorption bands of these compounds, making them potential
candidates for use in photodynamic therapy,5−8 and lowering
the HOMO−LUMO energy gap, which is relevant for
application as light-harvesters for dye-sensitized solar cells.9
Recent methods for the synthesis of porphyrins bearing one
to four β,β′-fused benzo-, naphtho-, or other polycyclic
aromatic groups involve a cascade reaction based on the
Heck reaction of polybromoporphyrins,5,6,9,10 the allylation of
polybromoporphyrins followed by ring-closure metathesis and
oxidation,11 the use of dihydroisoindoles,12−16 the electro-
cyclization of butadienylporphyrins,17 and the reaction of 2-
formyl-5,10,15,20-tetraphenylporphyrin with aryl methyl ke-
tones and ammonium acetate in the presence of La(OTf)3.18
Some years ago, Smith and collaborators reported the Diels−
Alder reaction of pyrroloporphyrin 1a with dimethyl
acetylenedicarboxylate (DMAD).19,20 This reaction leads to
the formation of a mixture of two isomeric bisadducts of type 2
(Scheme 1), which by thermal decomposition in refluxing 1,2,4-
trichlorobenzene (1,2,4-TCB) affords the benzoporphyrin
good yield, into the corresponding benzoporphyrin-22,23-
dicarboxylic anhydride 5, which is an excellent platform to
synthesize a range of interesting benzoporphyrin derivatives.
RESULTS AND DISCUSSION
■
The synthetic route to the benzoporphyrin-22,23-dicarboxylic
anhydride 5 is outlined in Scheme 1. The first step involved the
reaction of pyrrolo[3,4-b]porphyrin 1 with an excess of DMAD
in refluxing toluene for 1 h. A drastic color change (from dark
green to dark red) was observed, and the TLC of the reaction
mixture revealed the absence of the starting porphyrin and the
formation of a single product (Rf smaller than that of porphyrin
1). The mass (m/z = 1007) and 1H NMR spectra (four singlets
corresponding to methyl ester groups at 3.64, 3.70, 3.76, and
3.82 ppm) of the new dark red compound are compatible with
a bisadduct structure. The latter also shows three singlets at
1.98 (N−CH3), 5.39 (N−CH), and 7.21 (CCH) ppm.
Received: May 1, 2013
© XXXX American Chemical Society
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Scheme 1
Scheme 2
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Scheme 3
Scheme 4
1
These data and the correlations (3J) observed in the H−13C
HMBC spectrum fully support the structure 2 (Supporting
Information).
anhydride. After the evaporation of the acetic anhydride under
reduced pressure, the residue was crystallized from CH2Cl2/
MeOH, and compound 5 was obtained in quantitative yield as a
dark green solid. However, because we wanted to react
“phthalic” anhydride 5 with amines (requiring the prior
removal of the acetic anhydride), the following alternative
procedure to generate anhydride 5 was developed. Heating a
1,2,4-TCB solution of diacid 4 at reflux for 1 h, in the presence
of powdered 4Å molecular sieves, led to the total conversion of
the starting compound into anhydride 5. The subsequent
The next step consisted of the thermal decomposition of
compound 2 in refluxing 1,2,4-TCB. Purification by column
chromatography (silica gel) afforded a major fraction identified
by MS and NMR as benzoporphyrin-22,23-dicarboxylic ester 3
(53% yield). The conversion of the diester 3 into anhydride 5
involved the hydrolysis of the ester groups to the “phthalic”
acid 4 (90% yield) followed by dehydration in refluxing acetic
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Figure 1. Predominant conformation 11|| adopted by compound 11 in chloroform. Both fused-ring fragments (containing the porphyrinic units) lie
on the same plane, with the central benzenic ring only slightly deviating (∼10°) from coplanarity to the porphyrinic plane. Color code: oxygen, red;
nitrogen, blue; carbon, gray; nickel, green; hydrogen, white. All hydrogens, apart from Hb and Hf (shown as white spheres), were omitted for sake of
clarity.
Figure 2. Predominant conformation 11⊥ adopted by compound 11 in chloroform. Both fused-ring fragments are perpendicular to each other, with
the central benzenic ring forming an interplanar angle of ca. 70° with each of the fused-ring frames. Coding as in Figure 1.
addition of amines to the in situ generated anhydride resulted in
the formation of the expected “phthalimides”. This new
procedure allowed a one-pot conversion of diacid 4 into a
range of imides (Schemes 2 and 3) and other heterocyclic-fused
benzoporphyrin derivatives (Scheme 4).
11 and 12 were obtained, albeit in low yields (Scheme 3). The
formation of these bisporphyrins was confirmed by their mass
spectra (m/z = 1652).
The analysis of the NMR spectra of the bisporphyrins 11 and
12 raised interesting conformational issues. As expected, the 1H
NMR spectrum of compound 12 is compatible with a
symmetric structure, showing a singlet at δ 7.52 ppm assigned
to the resonances of the four protons of the “phthalimide”
groups and a singlet and two doublets at δ 8.69, 8.70, and 8.78
ppm, respectively, ascribed to the 12 β-pyrrolic protons. The
13C NMR spectrum of the free base 12a shows only one signal
corresponding to the resonances of the four carbonyl carbons at
167.1 ppm.23 Surprisingly, the 1H NMR spectrum of
compound 11 is more complex than anticipated for such a
symmetrical structure, exhibiting three singlets at δ 7.41, 7.53,
and 7.65 ppm (ascribed to the four protons of the
“phthalimide” groups and the four protons of the p-phenylene
group) and a multiplet at δ 8.68−8.79 ppm due to the 12 β-
pyrrolic protons. Moreover, the 13C NMR spectrum shows two
peaks at 167.4 and 168.6 ppm attributed to the resonances of
the carbonyl carbons. Initially, we considered the possibility of
having a mixture of two compounds (in a ca. 1:1 ratio), but this
was ruled out on the basis of the TLC (one spot) and the mass
spectrum. The multiplicity of the NMR signals of compound
11 was then attributed to the presence of different conforma-
tional isomers, a hypothesis that was confirmed by molecular
mechanics simulations (vide infra).
The reaction of the in situ generated anhydride 5 with
alkylamines and arylamines afforded phthalimides 6−10 in
moderate to quantitative yields. The reaction with alkylamines
(4-aminobenzylamine and pyridin-4-ylmethylamine) was much
faster (3 h) than with arylamines (16−72 h), reflecting the
differences in the reactivity of these two types of compounds.
These different reactivities also account for the regioselective
formation of imide 6, whose structural identity was supported
1
by the presence of a singlet at δ 4.70 ppm in the H NMR
spectrum that correlates with a carbonyl carbon in the 1H−13C
HMBC spectrum.
The reaction of anhydride 5 with 4-aminophthalonitrile and
5-(4-aminophenyl)-10,15,20-triphenylporphyrin (H2N-TPP)
afforded the expected imides 8 and 9 in 62% yield in both
cases. The structures of the new compounds were confirmed by
their mass and NMR spectra.
The reaction of anhydride 5 with benzene-1,4-diamine,
benzene-1,3-diamine and benzene-1,2-diamine was also con-
sidered. When a large excess of benzene-1,4-diamine was used,
imide 10 was obtained in quantitative yield (Scheme 2).
However, using 0.5 equiv of benzene-1,4-diamine or benzene-
1,3-diamine, the anticipated symmetric bisporphyrin derivatives
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Figure 3. Maps of fused- and central-ring current contributions (top and bottom rows, respectively) to the Hb and Hf chemical shifts in
conformations 11|| and 11⊥ (left and right columns, respectively), according to the Haigh−Mallion model. Protons on blue areas experience chemical
shielding, whereas those on red areas sustain chemical deshielding. The color code is different on both rows (−0.5 to 0.5 ppm in the upper row and
−0.1 to 0.1 ppm in the lower) and the magnitude of the contributions is qualitative; a single porphyrinic fragment is shown, for the sake of clarity.
Remaining details are given in Figure 1.
Another interesting modification of 5 involved its reaction
with benzene-1,2-diamine and naphthalene-1,8-diamine in
refluxing 1,2,4-TCB; porphyrins 13 and 14 were obtained in
36% and 30% yield, respectively (Scheme 4). The mass spectra
of the resulting products (m/z = 863 and m/z = 913,
respectively) confirm that, after the formation of the imide, an
intramolecular condensation between the remaining amino
group and the spatially close carbonyl group occurred. The
NMR data are also in agreement with the proposed structures.
The formation of this type of heterocyclic compounds from the
reaction of phthalic anhydrides and benzene-1,2-diamines (or
naphthalene-1,8-diamines) is known in the literature.24,25
The demetalation of phthalimides 6−10 and 12 and
compounds 13 and 14 was carried out with H2SO4/CH2Cl2
(1:9) at room temperature. In almost all cases, the
corresponding free bases were obtained in quantitative yield.
Molecular Mechanics/Dynamics Simulations. In order
to elucidate the multiplicity of the NMR signals of bisporphyrin
11, molecular mechanics simulations were performed. These
studies revealed that compound 11 exhibits two preferential
conformations, characterized by the arrangement of the fused-
ring frames relative to the central benzenic ring: a coplanar
arrangement (Figure 1; henceforth denoted 11||), where both
fused-ring frames are almost coplanar to the central ring plane,
and an almost perpendicular arrangement (Figure 2; 11⊥),
where the two frames make a ca. 70° interplanar angle with the
central benzenic plane.
solution. All-atom molecular dynamics simulations of 11|| and
11⊥ in chloroform showed that both conformations coexist in
solution, with no significant 11|| ↔ 11⊥ interconversion being
observed during the course of the several 100 ns long
simulations (Figures S41 and S42 in the Supporting
Information). Interactions of the chloroform molecules with
the carbonyl oxygen atoms (via Cl3C−H···OC hydrogen
bonding) are responsible for locking rotations about the
Cbenzene-N bond in 11⊥, whereas intramolecular CO···H−
Cbenzene hydrogen bonds forming a rather stable six-membered
ring account for the stabilization of conformation 11||. Both
mechanisms, along with the bulkiness of the porphyrinic
fragments, lead to a very slow rotation of the different ring
fragments about the Cbenzene-N bonds. Therefore, we submit
that both conformations coexist in solution with an
interconversion rate that is slow on the NMR time scale.
Accordingly, the relative disposition of the aromatic moieties in
both conformations renders magnetically unequivalent the
protons of the central benzylidene ring of the phthalimide units.
Therefore, in order to qualitatively study the conformational
dependence of the proton chemical shifts of 11, the
semiempirical Haigh−Mallion model26 was employed. Despite
its simplicity, this model accurately describes the contribution
to the chemical shifts of induced ring currents in systems
ranging from proteins to inclusion complexes. A recent work by
Zonta et al.27 has shown that the Haigh−Mallion model
correlates very well with nucleus-independent chemical shifts
(NICS), currently the method of choice for the assessment of
ring current contributions to chemical shifts in organic
molecules.
The interconversion 11|| ↔ 11⊥ occurs freely in the gas phase
due to the absence of significant intramolecular stereochemical
impediments. Interestingly, a different situation occurs in
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Figure 4. Predominant conformation of compound 12 in chloroform. Each of the fused-ring fragments form an interplanar angle of ca. 70° with the
central benzenic ring. Coding as in Figure 1.
(except when indicated) and tetramethylsilane (TMS) as internal
Conformation 11|| presents, on average, the protons of the
central and benzo-fused groups (henceforth denoted Hb and
Hf, respectively) on the molecular plane, outside the shielding
cones originated by the neighbor aromatic units (Figure 3, left
column), whereas conformation 11⊥ has the Hb protons on a
plane nearly perpendicular to both fused-ring frames (Figure 3,
right column). Hence, the ring current effects due the fused
ring systems contribute differently to the Hb protons chemical
shifts, such that these are expected to be more deshielded in
conformation 11||. In a similar way, the contributions to the
central benzenic ring Hf chemical shifts are also expected to be
different, being also more deshielded in conformation 11||.
These results justify the break of symmetry patent in the
experimental spectra.
reference. The chemical shifts are expressed in δ (ppm) and the
1
coupling constants in hertz. Unequivocal H assignments were made
using 2D COSY and NOESY experiments (mixing time of 800 ms),
while 13C assignments were made on the basis of 2D HSQC and
HMBC experiments (delay for long-range J C/H couplings were
optimized for 7 Hz). Mass spectra and HRMS were recorded using
CHCl3 as solvent (except when indicated) and 3-nitrobenzyl alcohol
(NBA) as matrix. The UV−vis spectra were recorded using CHCl3 as
solvent. Column chromatography was carried in silica gel (230−400
mesh). Preparative thin-layer chromatography was carried out on 20
cm × 20 cm glass plates coated with silica gel (0.5 mm thick).
Analytical TLC was carried out on precoated sheets with silica gel (0.2
mm thick). All solvents and reagents were used without further
purification.
Tetramethyl 1-Methyl-7,12,17,22-tetraphenyl-3a,23b-dihy-
dro-1H-pyrrolo[3,2-a]benzoporphyrin-2,3,3a,4-tetracarboxy-
late Nickel(II) Complex, 2. Dimethyl acetylenedicarboxylate (500
μL) was added to a solution of pyrroloporphyrin 121 (500.0 mg, 0.690
mmol) in toluene (30 mL), and the reaction mixture was stirred at
reflux for 1 h. During the reflux, a drastic change in color (from dark
green to dark red) was observed, and at the end, the starting porphyrin
was not detected by TLC. After cooling, the toluene was evaporated
under reduced pressure, and the product was crystallized from
dichloromethane/light petroleum. Compound 2 was obtained in
quantitative yield (695.0 mg) as a dark red solid. 1H NMR (300 MHz;
CDCl3) δ 1.98 (s, 3H), 3.64, 3.70, 3.76, 3.82 (4s, 12H), 5.39 (s, 1H),
7.21 (s, 1H), 7.63−7.79 (m, 14H), 7.95−7.98 (m, 6H), 8.46 (d, 1H, J
= 5.1 Hz), 8.58 (d, 1H, J = 5.1 Hz), 8.64 (d, 1H, J = 5.1 Hz), 8.67 (d,
1H, J = 5.0 Hz), 8.69 (d, 1H, J = 5.0 Hz), 8.78 (d, 1H, J = 5.1 Hz); 13C
NMR (125 MHz, CDCl3) δ 31.9, 50.8, 51.3, 51.7, 51.8, 69.1, 104.3,
118.5, 119.1, 119.2, 124.8, 127.0, 127.2, 127.8, 127.9, 128.1, 128.2,
128.8, 129.1, 129.2, 131.7, 132.1, 132.2, 132.5, 132.6, 132.7, 132.8,
132.9, 133.2, 133.3, 133.4, 133.6, 133.7, 133.8, 136.6, 137.7, 138.9,
139.1, 139.9, 139.96, 139.97, 143.2, 143.3, 143.4, 143.55, 143.63,
143.9, 154.1, 154.2, 163.4, 164.7, 166.2, 171.0; HRMS (ESI-FTICR)
m/z [M]+• calcd for C59H43N5NiO8 1007.2460, found 1007.2458;
UV−vis (CHCl3) λmax (log ε) 436 (5.18), 548 (4.08), 590 (4.05) nm.
Dimethyl 5,10,15,20-Tetraphenylbenzoporphyrin-22,23-di-
carboxylate (Nickel(II) Complex and Free Base), 3 and 3a. A
solution of porphyrin 2 (40.0 mg, 39.7 μmol) in 1,2,4-trichlor-
obenzene (1,2,4-TCB) (5 mL) was heated at reflux for 48 h. After
cooling, the reaction mixture was submitted to column chromatog-
raphy (silica gel) using light petroleum and then dichloromethane as
eluents; the first fraction was benzoporphyrin 3 (35.0 mg, 53% yield).
The demetalation of compound 3 (10.0 mg) was carried out with
H2SO4/CH2Cl2 (1:9) (1 mL). After stirring at room temperature for 5
min, the mixture was neutralized with aqueous sodium carbonate and
extracted with dichloromethane. The organic phase was dried over
Na2SO4, and after evaporation of the solvent under reduced pressure,
A similar analysis was performed for compound 12. Although
a comparable discussion of the ring current contributions to the
Hb and Hf chemical shifts was carried out, compound 12 was
found to possess only one preferable conformation in
chloroform, one in which the central benzenic ring forms,
simultaneously, a ca. 70° interplanar angle with both
porphyrinic fragments (Figure 4; see also Figures S49 and
S50 in Supporting Information). Hence, both Hb and Hf
protons experience, essentially, a single magnetic environment
and, thus, exhibit no resonance splitting, in accord with the
experimental spectra.
CONCLUSION
■
A synthetic route to meso-tetraphenylbenzoporphyrin-22,23-
dicarboxylic anhydride was reported. As shown in Scheme 2,
this anhydride reacts with alkylamines and arylamines to afford
the corresponding N-substituted “phthalimides” in moderate to
excellent yields. The new “phthalimides” may be used in
subsequent transformations: for instance, compounds 6 and 10
may be further functionalized at the amino group, the pyridyl
group in 7 may be used for constructing supramolecular
systems or cationization, and 8 may be a precursor of
phthalocyanines bearing benzoporphyrin units.
Since the title compound reacts like phthalic anhydride, it is
expected that it may be used to decorate any primary amine, or
polyamines, with benzoporphyrin units.
EXPERIMENTAL SECTION
■
General Information. 1H and 13C NMR spectra were recorded in
two NMR spectrometers operating at 500.13 and 125.77 MHz or at
300.13 and 75.47 MHz, respectively. CDCl3 was used as solvent
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the residue was crystallized from CH2Cl2/MeOH. Porphyrin 3a was
obtained in quantitative yield (9.3 mg).
of 4-aminobenzylamine (42.0 μL, 10 equiv) in dry pyridine (3 mL)
was added to the reaction mixture, which was stirred at reflux (220 °C)
for 3 h. After cooling, the reaction mixture was neutralized with an
aqueous solution of citric acid, extracted with CH2Cl2, and evaporated
under reduced pressure. The product was submitted to column
chromatography (silica gel); light petroleum was used to remove the
1,2,4-TCB, and then CH2Cl2 was used to elute phthalimide 6, which
was obtained in quantitative yield (33.0 mg). The demetalation of
compound 6 (10.0 mg) was carried out with H2SO4/CH2Cl2 (1:9) (1
mL). After stirring at room temperature for 5 min, the mixture was
neutralized with aqueous sodium carbonate and extracted with
dichloromethane. The organic phase was dried over Na2SO4, and
after evaporation under reduced pressure, the residue was crystallized
from CH2Cl2/MeOH. Porphyrin 6a was obtained in quantitative yield
(9.3 mg).
3: 1H NMR (300 MHz; CDCl3) δ 3.87 (s, 6H), 7.39 (s, 2H), 7.66−
7.85 (m, 12H), 7.90−7.99 (m, 8H), 8.67−8.74 (m, 6H); HRMS (ESI-
FTICR) m/z [M]+• calcd for C52H36N4O4 836.1928, found 836.1948;
UV−vis (CHCl3) λmax (log ε) 432 (5.27), 545 (4.16), 578 (3.97) nm.
1
3a: H NMR (300 MHz; CDCl3) δ −2.67 (s, 2H), 3.90 (s, 6H),
7.39 (s, 2H), 7.75−7.93 (m, 12H), 8.17−8.23 (m, 8H), 8.71 (s, 2H),
8.87 (d, 2H, J = 5.0 Hz), 8.91 (d, 2H, J = 5.0 Hz); 13C NMR (125
MHz, CDCl3) δ 52.4, 118.0, 121.3, 125.9, 126.8, 127.86, 127.90, 128.1,
128.5, 129.0, 133.7, 134.1, 134.5, 141.7, 142.0, 143.1, 168.5; HRMS
+
(ESI-FTICR) m/z [M + H]+ calcd for C52H35N4NiO4 781.2809,
found 781.2790; UV−vis (CHCl3) λmax (log ε) 430 (5.53), 521 (4.40),
554 (3.60) (shoulder), 655 (3.04) nm.
5,10,15,20-Tetraphenylbenzoporphyrin-22,23-dicarboxylic
Acid (Nickel(II) Complex and Free Base), 4 and 4a. A solution of
KOH (550.0 mg) in methanol (7.5 mL) was added to a solution of
diester 3 (35.0 mg, 41.9 μmol) in THF (2 mL) and pyridine (150 μL).
The reaction mixture was stirred at reflux for 48 h. After this time, no
starting material was detected by TLC. After cooling, the reaction
mixture was neutralized with an aqueous solution of citric acid and
extracted with CH2Cl2. After evaporation under reduced pressure, the
product was submitted to column chromatography (silica gel) using
CH2Cl2 and then CH2Cl2/MeOH (9.5:0.5) as the eluents. The major
fraction was “phthalic” acid 4 (30.5 mg, 90% yield). The demetalation
of compound 4 (10.0 mg) was carried out with H2SO4/CH2Cl2 (1:9)
(1 mL). After stirring at room temperature for 5 min, the mixture was
neutralized with aqueous sodium carbonate and extracted with
dichloromethane. The organic phase was dried over Na2SO4, and
after evaporation under reduced pressure, the residue was crystallized
from CH2Cl2/MeOH. Porphyrin 4a was obtained in quantitative yield
(9.3 mg).
6: 1H NMR (300 MHz, CDCl3) δ 4.70 (s, 2H), 6.65 (d, 2H, J = 8.5
Hz), 7.29 (d, 2H, J = 8.5 Hz), 7.40 (s, 2H), 7.63−7.78 (m, 10H),
7.84−7.98 (m, 10H), 8.66−8.68 (m, 4H), 8.73 (d, 2H, J = 5.0 Hz);
13C NMR (75 MHz, CDCl3) δ 41.3, 115.5, 116.6, 119.5, 120.2, 127.1,
127.8, 128.0, 128.3, 129.1, 130.3, 132.1, 132.2, 132.6, 132.9, 133.5,
136.5, 139.98, 140.02, 141.7, 142.3, 143.3, 143.5, 168.2; MS (MALDI-
FTICR) m/z [M + H]+ calcd for C57H37N6NiO2 895.2326, found
895.2313; UV−vis (CHCl3) λmax (log ε) 445 (5.41), 552 (4.29), 587
(4.20) nm.
1
6a: H NMR (300 MHz, CDCl3) δ −2.67 (s, 2H), 4.72 (s, 2H),
6.61 (d, 2H, J = 9.0 Hz), 7.26−7.29 (m, 2H, overlapped with the
CHCl3 signal), 7.39 (s, 2H), 7.74−7.80 (m, 6H), 7.84−7.89 (m, 4H),
7.97−8.02 (m, 2H), 8.18−8.23 (m, 8H), 8.71 (s, 2H), 8.88 and 8.91
(AB system, 4H, J = 5.1 Hz); 13C NMR (75 MHz, CDCl3): 41.3,
115.0, 118.5, 119.9, 121.2, 126.9, 127.9, 128.0, 128.1, 128.5, 129.0,
129,1, 130.2, 133.7, 134.5, 138.6, 139.2, 141.6, 141.9, 145.5, 145.9,
168.4; HRMS (ESI-FTICR) m/z [M + H]+ calcd for C57H39N6O2
839.3129, found 839.3125; UV−vis (CHCl3) λmax (log ε) 441 (5.22),
526 (4.13), 562 (3.63), 604 (3.68), 662 (3.12) nm.
1
4: H NMR (300 MHz; DMSO-d6) δ 7.39 (broad s, 2H), 7.74−
7.86 (m, 12H), 7.93−7.99 (m, 8H), 8.70−8.75 (m, 6H); 13C NMR
(125 MHz, DMSO-d6) δ 116.0, 120.4, 127.6, 128.5, 129.2, 132.5,
132.6, 133.0, 133.4, 133.9, 136.7, 139.3, 139.5, 141.1, 141.2, 142.0,
143.7, 168.9; HRMS (ESI-FTICR) m/z [M]+• calcd for C50H32N4O4
808.1615, found 808.1623; UV−vis (CHCl3) λmax (log ε) 437 (5.13),
549 (4.04), 583 (3.88) nm.
5,10,15,20-Tetraphenyl-N-(pyridin-4-ylmethyl)-
benzoporphyrin-22,23-dicarboximide (Nickel(II) Complex and
Free Base), 7 and 7a. Powdered 4Å molecular sieves (7.0 mg) were
added to a solution of “phthalic” acid 4 (6.5 mg, 8.4 μmol) in 1,2,4-
TCB (0.7 mL), and the mixture was stirred at reflux for 1 h. After
cooling to rt, a solution of pyridin-4-ylmethylamine (100.0 μL) in dry
pyridine (0.7 mL) was added to the reaction mixture, which was
stirred at reflux (220 °C) for 3 h. After cooling, the reaction mixture
was neutralized with an aqueous solution of citric acid, extracted with
CH2Cl2, and evaporated under reduced pressure. The product was
submitted to column chromatography (silica gel); light petroleum was
used to remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
phthalimide 7, which was obtained in 33% yield (2.4 mg). The
demetalation of compound 7 (4.0 mg) was carried out with H2SO4/
CH2Cl2 (1:9) (0.4 mL). After stirring at room temperature for 5 min,
the mixture was neutralized with aqueous sodium carbonate and
extracted with dichloromethane. The organic phase was dried over
Na2SO4, and after evaporation under reduced pressure, the residue was
crystallized from CH2Cl2/MeOH. Porphyrin 7a was obtained in
quantitative yield (3.4 mg).
1
4a: H NMR (300 MHz; DMSO-d6) δ −2.77 (s, 2H), 7.60 (broad
s, 2H), 7.83−7.96 (m, 12H), 8.20−8.24 (m, 8H), 8.65 (s, 2H), 8.84
(d, 2H, J = 5.1 Hz), 8.94 (d, 2H, J = 5.1 Hz); 13C NMR (125 MHz,
DMSO-d6) δ 118.1, 121.3, 127.4, 128.4, 128.5, 129.3, 133.4, 134.4,
141.1, 141.4, 142.3, 169.0; HRMS (ESI-FTICR) m/z [M + H]+ calcd
for C50H31N4NiO4 753.2496, found 753.2486; UV−vis (CHCl3) λmax
(log ε) 434 (5.26), 525 (4.36), 601 (3.91), 660 (3.20) nm.
5,10,15,20-Tetraphenylbenzoporphyrin-22,23-dicarboxylic
Anhydride Nickel(II) Complex, 5. A solution of “phthalic” acid 4
(50.0 mg, 61.9 μmol) in acetic anhydride (15 mL) was stirred at reflux
for 1 h. After this time, no starting material was detected by TLC. The
acetic anhydride was evaporated under reduced pressure. (Note: small
amounts of toluene (15 mL) were added to the reaction mixture
during this process to facilitate the total evaporation of the acetic
anhydride). Compound 5 was obtained quantitatively (48.8 mg) as a
dark green solid after crystallization from CH2Cl2/MeOH. Alter-
natively, compound 5 can be prepared by refluxing a solution of
“phthalic” acid 4 (30.0 mg) in 1,2,4-TCB (3 mL) for 1 h in the
1
7: H NMR (300 MHz, CDCl3) δ 4.80 (s, 2H), 7.32−7.42 (broad
m, 2H), 7.45−7.61 (m, 2H), 7.64−7.81 (m, 12H), 7.86−7.99 (m,
10H), 8.68−8.70 (m, 4H), 8.76 (d, 2H, J = 5.0 Hz); 13C NMR (75
MHz, CDCl3) δ 39.9, 116.7, 119.9, 120.3, 127.1, 127.2, 128.0, 128.4,
129.1, 132.2, 132.4, 132.7, 133.0, 133.5, 136.3, 139.9, 140.0, 141.90,
142.5, 143.4, 143.5, 167.9; HRMS (ESI-FTICR) m/z [M + H]+ calcd
for C56H35N6NiO2 881.2169, found 881.2153.
1
presence of powdered 4Å molecular sieves (30.0 mg). H NMR (300
MHz, CDCl3) δ 7.56 (s, 2H), 7.68−7.70 (m, 6H), 7.77−7.82 (m, 6H),
7.91−7.99 (m, 8H), 8.69−8.71 (m, 4H), 8.75−8.77 (m, 2H); 13C
NMR (125 MHz, CDCl3) δ 116.9, 120.5, 121.8, 125.8, 127.2, 128.1,
128.5, 129.3, 132.4, 132.60, 132.62, 133.2, 133.5, 135.6, 139.7, 139.8,
142.1, 142.7, 143.5, 144.2, 163.4; HRMS (ESI-FTICR) m/z [M]+•
calcd for C50H28N4NiO3 790.1509, found 790.1504; UV−vis (CHCl3)
λmax (log ε) 436 (4.37), 451 (5.27), 556 (4.21), 596 (4.17) nm.
N-(4-Aminobenzyl)-5,10,15,20-tetraphenylbenzoporphyrin-
22,23-dicarboximide (Nickel(II) Complex and Free Base), 6 and
6a. Powdered 4Å molecular sieves (30.0 mg) were added to a solution
of “phthalic” acid 4 (30.0 mg, 37.1 μmol) in 1,2,4-TCB (3 mL), and
the mixture was stirred at reflux for 1 h. After cooling to rt, a solution
7a 1H NMR (300 MHz, CDCl3) δ −2.66 (s, 2H), 4.83 (s, 2H), 7.32
(dd, 2H, J = 4.6 and 1.6 Hz), 7.44 (s, 2H), 7.73−7.81, 7.85−7.91,
7.97−8.03, 8.19−8.23 (4m, 20H), 8.54 (dd, 2H, J = 4.6 and 1.6 Hz),
8.72 (s, 2H), 8.90 and 8.92 (AB system, 4H, J = 5.1 Hz); 13C NMR
(75 MHz, CDCl3): 40.6, 118.6, 120.2, 121.3, 123.1, 126.9, 128.0,
128.1, 128.4, 128.6, 129.1, 133.7, 134.4, 134.5, 138.7, 139.1, 141.6,
141.8, 145.2, 145.7, 150.1, 168.1; MS (MALDI) m/z [M + H]+ calcd
for C56H37N6O2 825.3, found 825.3; UV−vis (CHCl3) λmax (log ε) 446
(5.36), 530 (4.31), 566 (3.87), 607 (3.89), 666 (3.36) nm.
G
dx.doi.org/10.1021/jo400948s | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
1
N-(3,4-Dicyanophenyl)-5,10,15,20-tetraphenylbenzopor-
phyrin-22,23-dicarboximide (Nickel(II) Complex and Free
Base), 8 and 8a. Powdered 4Å molecular sieves (8.5 mg) were
added to a solution of “phthalic” acid 4 (8.0 mg, 10.5 μmol) in 1,2,4-
TCB (1 mL), and the mixture was stirred at reflux for 1 h. After
cooling to rt, a solution of 4-aminophthalonitrile (25.0 mg, 174.7
μmol, ∼17 equiv) in dry pyridine (1 mL) was added to the reaction
mixture and it was stirred, at reflux (220 °C), for 24 h. After cooling,
the reaction mixture was neutralized with an aqueous solution of citric
acid, extracted with CH2Cl2 and evaporated under reduced pressure.
The product was submitted to column chromatography (silica gel);
light petroleum was used to remove the 1,2,4-TCB and then CH2Cl2
was used to elute phthalimide 8, which was obtained in 62% yield (6.0
mg). The demetalation of compound 8 (5.0 mg) was carried out with
H2SO4/CH2Cl2 (1:9) (0.5 mL). After stirring at room temperature for
5 min, the mixture was neutralized with aqueous sodium carbonate
and extracted with dichloromethane. The organic phase was dried over
Na2SO4 and, after evaporation under reduced pressure, the residue was
crystallized from CH2Cl2/MeOH. Porphyrin 8a was obtained in
quantitative yield (4.6 mg).
9a: H NMR (300 MHz, CDCl3) δ −2.76 (s, 2H), −2.59 (s, 2H),
7.60 (s, 2H), 7.76−7.82, 7.90−7.98, 8.04−8.09, 8.23−8.37 (4m, 40H),
8.75 (s, 2H), 8.86−8.99 (m, 12H); 13C NMR (75 MHz, CDCl3) δ
118.7, 119.0, 120.2, 120.6, 121.36, 124.44, 126.7, 126.9, 127.7, 128.0,
128.2, 128.4, 128.7, 129.2, 131.9, 133.8, 134.4, 134.6, 134.9, 138.8,
139.2, 141.6, 141.9, 142.2, 146.0, 148.3, 155.5, 167.9; HRMS (ESI-
FTICR) m/z [M + H]+ calcd for C94H59N9O2 1346.4870, found
1346.4865; UV−vis (CHCl3) λmax (log ε) 417 (5.43), 443 (5.38), 523
(4.38), 555 (3.97), 602 (3.90), 644 (3.53), 657 (3.30) nm.
N-(4-Aminophenyl)-5,10,15,20-tetraphenylbenzoporphyrin-
22,23-dicarboximide (Nickel(II) Complex and Free Base), 10
and 10a. Powdered 4Å molecular sieves (10.0 mg) were added to a
solution of “phthalic” acid 4 (10.0 mg, 12.4 μmol) in 1,2,4-TCB (1.2
mL), and the mixture was stirred at reflux for 1 h. A solution of
benzene-1,4-diamine (50.0 mg) in dry pyridine (1.2 mL) was added to
the reaction mixture, which was stirred at reflux (220 °C) for 16 h.
After cooling, the reaction mixture was neutralized with an aqueous
solution of citric acid, extracted with CH2Cl2, and evaporated under
reduced pressure. The product was submitted to column chromatog-
raphy (silica gel); light petroleum was used to remove the 1,2,4-TCB,
and then CH2Cl2 was used to elute phthalimide 10, which was
obtained in quantitative yield (10.7 mg). The demetalation of
compound 10 (10.0 mg) was carried out with H2SO4/CH2Cl2 (1:9)
(1 mL). After stirring at room temperature for 5 min, the mixture was
neutralized with aqueous sodium carbonate and extracted with
dichloromethane. The organic phase was dried over Na2SO4, and
after evaporation under reduced pressure, the residue was crystallized
from CH2Cl2/MeOH. Porphyrin 10a was obtained in quantitative
yield (9.2 mg).
1
8: H NMR (300 MHz, CDCl3) δ 7.53 (s, 2H), 7.66−7.72, 7.78−
7.83, 7.87−7.99 (3m, 21H), 8.08 (dd, 1H, J = 8.6 and 2.1 Hz), 8.20 (d,
1H, J = 2.1 Hz), 8.71 (m, 4H), 8.78 (d, 2H, J = 5.0 Hz); 13C NMR (75
MHz, CDCl3) δ 113.9, 115.2, 115.5, 117.1, 117.3, 120.9, 121.1, 126.3,
127.6, 128.6, 128.9, 129.5, 129.6, 129.9, 132.8, 133.05, 133.13, 133.6,
134.0, 134.5, 136.4, 137.4, 140.2, 140.4, 142.6, 143.1, 143.9, 144.3,
145.2, 166.5; HRMS (ESI-FTICR) m/z [M]+• calcd for
C58H31N7NiO2 915.1887, found 915.1878; UV−vis (CHCl3) λmax
(log ε) 452 (5.17), 555 (4.27), 596 (4.27) nm.
1
10: H NMR (300 MHz, CDCl3) δ 6.75 (d, 2H, J = 8.6 Hz), 7.19
1
8a: H NMR (300 MHz, CDCl3) δ −2.64 (s, 2H), 7.50 (s, 2H),
(d, 2H, J = 8.6 Hz), 7.47 (s, 2H), 7.66−8.00 (m, 20H), 8.69 (s, 2H),
8.70 (d, 2H, J = 4.9 Hz), 8.77 (d, 2H, J = 4.9 Hz); 13C NMR (75 MHz,
CDCl3) δ 115.1, 116.6, 119.8, 120.3, 122.6, 127.1, 127.4, 127.6, 128.0,
128.4, 129.1, 132.1, 132.3, 132.7, 132.9, 133.5, 136.5, 139.96, 140.02,
141.7, 142.4, 143.5, 143.6, 146.1, 167.8; HRMS (ESI-FTICR) m/z [M
+ H]+ calcd for C56H35N6NiO2 881.2169, found 881.2158; UV−vis
(CHCl3) λmax (log ε) 446 (5.20), 552 (4.16), 590 (4.09) nm.
10a: 1H NMR (300 MHz; CDCl3) δ −2.63 (s, 2H), 6.75 (d, 2H, J =
8.6 Hz), 7.20 (d, 2H, J = 8.6 Hz), 7.46 (s, 2H), 7.76−7.80 (m, 6H),
7.84−7.89 (m, 4H), 7.95−8.00 (m, 2H), 8.20−8.24 (m, 8H), 8.72 (s,
2H), 8.91 (AB system, 4H, J = 5.2 Hz); HRMS (ESI-FTICR) m/z [M
+ H]+ calcd for C56H37N6O2 825.2973, found 825.2967; UV−vis
(CHCl3) λmax (log ε) 443 (5.18), 527 (4.07), 563 (3.60), 604 (3.63),
663 (3.07) nm.
7.76−7.83 (m, 6H), 7.85 (d, 1H, J = 8.5 Hz), 7.88−7.93 (m, 4H),
8.01−8.04 (m, 2H), 8.07 (dd, 1H, J = 8.5 and 2.1 Hz), 8.20−8.25 (m,
9H), 8.74 (s, 2H), 8.93 and 8.96 (AB system, 4H, J = 5.1 Hz); 13C
NMR (75 MHz, CDCl3) δ 113.3, 114.8, 115.1, 116.6, 118.7, 121.0,
121.5, 126.9, 126.9, 127.0, 127.9, 128.0, 128.1, 128.2, 128.8, 128.9,
129.2, 129.4, 133.7, 134.0, 134.5, 137.0, 138.9, 139.1, 141.4, 141.7,
146.2, 147.6, 155.7, 166.3; HRMS (ESI-FTICR) m/z [M + H]+ calcd
for C58H33N7O2 860.2769, found 860.2764; UV−vis (CHCl3) λmax
(log ε) 449 (5.17), 529 (4.28), 567 (3.92), 608 (3.88), 665 (3.37) nm.
N-[4-(10,15,20-Triphenylporphyrin-5-yl)phenyl]-5,10,15,20-
tetraphenylbenzoporphyrin-22,23-dicarboximide (Nickel(II)
Complex and Free Base), 9 and 9a. Powdered 4Å molecular
sieves (9.0 mg) were added to a solution of “phthalic” acid 4 (8.9 mg,
11.0 μmol) in 1,2,4-TCB (1 mL) and the mixture was stirred at reflux
for 1 h. After cooling to rt, a solution of H2N-TPP28 (7.0 mg, 1 equiv)
in dry pyridine (1 mL) was added to the reaction, and the mixture was
stirred at reflux (220 °C) for 72 h. After cooling, the reaction mixture
was neutralized with an aqueous solution of citric acid, extracted with
CH2Cl2, and evaporated under reduced pressure. The product was
submitted to column chromatography (silica gel); light petroleum was
used to remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
dyad 9, which was obtained in 62% yield (9.6 mg). The demetalation
of compound 9 (3.0 mg) was carried out with H2SO4/CH2Cl2 (1:9)
(0.3 mL). After stirring at room temperature for 5 min, the mixture
was neutralized with aqueous sodium carbonate and extracted with
dichloromethane. The organic phase was dried over Na2SO4, and after
evaporation under reduced pressure, the residue was crystallized from
CH2Cl2/MeOH. Porphyrin 9 was obtained in quantitative yield (2.8
mg).
Bisporphyrin 11. Powdered 4Å molecular sieves (9.0 mg) were
added to a solution of “phthalic” acid 4 (7.9 mg, 9.8 μmol) in 1,2,4-
TCB (1 mL), and the mixture was stirred at reflux for 1 h. A solution
of benzene-1,4-diamine (0.53 mg, 4.9 μmol, 0.5 equiv) in dry pyridine
(1 mL) was added to the reaction mixture, which was stirred at reflux
(220 °C) for 16 h. After cooling, the reaction mixture was neutralized
with an aqueous solution of citric acid, extracted with CH2Cl2, and
evaporated under reduced pressure. The product was submitted to
column chromatography (silica gel); light petroleum was used to
remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
1
phthalimide 11 (2.0 mg, 12% yield). H NMR (300 MHz; CDCl3)
δ 7.41 (s, 2H), 7.53 (s, 3H), 7.65 (s, 3H), 7.67−7.72 (m, 12H), 7.76−
7.87 (m, 8H), 7.95−8.01 (m, 20H), 8.68−8.79 (m, 12H); 13C NMR
(126 MHz, CDCl3) δ 116.6, 116.7, 119.4, 120.1, 120.3, 126.3, 127.1,
127.8, 128.0, 128.3, 128.4, 129.1, 129.2, 132.1, 132.2, 132.26, 132.33,
132.7, 132.9, 133.0, 133.5, 136.4, 136.5, 140.0, 141.7, 141.8, 142.38,
142.44, 143.3, 143.6, 143.7, 167.4, 168.6; HRMS (ESI-FTICR) m/z
[M]+• calcd for C106H60N10Ni2O4 1652.3501, found 1652.3483; UV−
vis (CHCl3) λmax (log ε) 387 (4.58), 450 (5.53), 554 (4.49), 592
(4.46) nm.
Bisporphyrins 12 and 12a. Powdered 4Å molecular sieves (9.5
mg) were added to a solution of “phthalic” acid 4 (10.5 mg, 13.0
μmol) in 1,2,4-TCB (1 mL), and the mixture was stirred at reflux for 1
h. A solution of benzene-1,3-diamine (0.70 mg, 6.5 μmol, 0.5 equiv) in
dry pyridine (1 mL) was added to the reaction mixture, which was
stirred at reflux (220 °C) for 16 h. After cooling, the reaction mixture
1
9: H NMR (300 MHz, CDCl3) δ −2.78 (s, 2H), 7.60 (s, 2H),
7.67−7.79 (m, 16H), 7.83−7.95 (m, 8H), 7.99−8.03 (m, 8H), 8.21−
8.25 (m, 6H), 8.34 (d, 2H, J = 8.3 Hz), 8.72−8.74 (m, 4H), 8.83 (d,
2H, J = 5.0 Hz), 8.86−8.93 (m, 8H); 13C NMR (75 MHz, CDCl3) δ
116.8, 119.0, 120.2, 120.3, 120.36, 124.42, 126.7, 127.1, 127.2, 127.7,
128.0, 128.5, 129.2, 131.8, 132.2, 132.4, 132.8, 133.0, 133.6, 134.6,
134.9, 136.4, 140.0, 140.1, 141.6, 141.9, 142.1, 142.5, 143.6, 143.7,
167.6; HRMS (ESI-FTICR) m/z [M + H]+ calcd for C94H58N9NiO2
1402.4067, found 1402.4084; UV−vis (CHCl3) λmax (log ε) 417
(5.59), 446 (5.38), 513 (4.46), 550 (4.53), 589 (4.46), 645 (3.96) nm.
H
dx.doi.org/10.1021/jo400948s | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
was neutralized with an aqueous solution of citric acid, extracted with
CH2Cl2, and evaporated under reduced pressure. The product was
submitted to column chromatography (silica gel); light petroleum was
used to remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
dimer 12 (4.0 mg, 19% yield). The demetalation of compound 12 (8.0
mg) was carried out with H2SO4/CH2Cl2 (1:9) (1 mL). After stirring
at room temperature for 5 min, the mixture was neutralized with
aqueous sodium carbonate and extracted with dichloromethane. The
organic phase was dried over Na2SO4, and after evaporation under
reduced pressure, the residue was crystallized from CH2Cl2/MeOH.
Porphyrin 12a was obtained in quantitative yield (7.3 mg).
was neutralized with an aqueous solution of citric acid, extracted with
CH2Cl2, and evaporated under reduced pressure. The product was
submitted to column chromatography (silica gel); light petroleum was
used to remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
porphyrin 14 (6.0 mg, 30%). The demetalation of compound 14 (5.0
mg) was carried out with H2SO4/CH2Cl2 (1:9) (0.5 mL). After
stirring at room temperature for 5 min, the mixture was neutralized
with aqueous sodium carbonate and extracted with dichloromethane.
The organic phase was dried over Na2SO4, and after evaporation under
reduced pressure, the residue was crystallized from CH2Cl2/MeOH.
Porphyrin 14a was obtained in 96% yield (4.5 mg).
1
1
12: H NMR (300 MHz, CDCl3) δ 7.52 (s, 4H), 7.55−7.59 (m,
14: H NMR (300 MHz, CDCl3) δ 7.41−7.55 (m, 5H), 7.60 (s,
3H), 7.65−7.71, 7.76−7.83, 7.86−7.91, 7.95−8.01 (4m, 41H), 8.69 (s,
4H), 8.70 (d, 4H, J = 4.9 Hz), 8.78 (d, 4H, J = 4.9 Hz); MS (MALDI-
FTICR) m/z [M + H]+ calcd for C106H61N10Ni2O4 1653.3579, found
1653.3560; UV−vis (CHCl3) λmax (log ε) 448 (5.03), 560 (4.17), 597
(4.18) nm.
1H), 7.66−7.71 (m, 6H), 7.79 (s, 1H), 7.82−7.88 (m, 4H), 7.94−8.01
(m, 10H), 8.51 (d, 1H, J = 7.5 Hz), 8.68−8.70 (m, 4H), 8.75−8.78
(m, 2H); 13C NMR (75 MHz, CDCl3) δ 109.4, 116.2, 116.4, 118.3,
119.9, 120.3, 120.4, 121.9, 122.8, 125.0, 126.4, 127.1, 127.7, 128.0,
128.5, 128.9, 129.1, 131.9, 132.1, 132.7, 132.8, 132.85, 132.92, 133.5,
134.1, 136.7, 139.7, 140.1, 140.2, 140.3, 142.2, 143.4, 143.67, 143.72,
149.1, 164.8; HRMS (ESI-FTICR) m/z [M + H]+ calcd for
C60H35N6NiO 913.2220, found 913.2211; UV−vis (CHCl3) λmax
(log ε) 447 (5.14), 555 (4.43), 596 (4.60) nm.
1
12a: H NMR (300 MHz, CDCl3) δ −2.61 (s, 4H), 7.52 (s, 4H),
7.58−7.62 (m, 3H); 7.75−7.82, 7.89−7.93, 7.98−8.04, 8.23−8.27
(4m, 41H); 8.74 (s, 4H), 8.94 (s, 8H); 13C NMR (75 MHz, CDCl3) δ
118.7, 120.5, 121.3, 123.4, 124.9, 126.9, 127.9, 128.1, 128.1, 128.2,
128.6, 129.2, 132.6, 133.7, 134.3, 134.6, 138.7, 139.2, 141.6, 141.8,
145.9, 148.6, 155.6, 167.1; HRMS (ESI-FTICR) m/z [M + H]+ calcd
for C106H65N10O4 1541.5190, found 1541.5176; UV−vis (CHCl3) λmax
(log ε) 446 (5.54), 527 (4.47), 564 (4.03), 605 (4.05), 662 (3.44) nm.
Compounds 13 and 13a. Powdered 4Å molecular sieves (18.0
mg) were added to a solution of “phthalic” acid 4 (17.6 mg, 13.0
μmol) in 1,2,4-TCB (1.8 mL), and the mixture was stirred at reflux for
1 h. A solution of benzene-1,2-diamine (2.4 mg, 1 equiv) in dry
pyridine (1.5 mL) was added to the reaction mixture, which was
stirred at reflux (220 °C) for 16 h. After cooling, the reaction mixture
was neutralized with an aqueous solution of citric acid, extracted with
CH2Cl2, and evaporated under reduced pressure. The product was
submitted to column chromatography (silica gel); light petroleum was
used to remove the 1,2,4-TCB, and then CH2Cl2 was used to elute
porphyrin 13 (7.0 mg; 36% yield). The demetalation of compound 13
(5.0 mg) was carried out with H2SO4/CH2Cl2 (1:9) (0.5 mL). After
stirring at room temperature for 5 min, the mixture was neutralized
with aqueous sodium carbonate and extracted with dichloromethane.
The organic phase was dried over Na2SO4, and after evaporation under
reduced pressure, the residue was crystallized from CH2Cl2/MeOH.
Porphyrin 13a was obtained in 96% yield (4.5 mg).
1
14a: H NMR (300 MHz, CDCl3) δ −2.81 (s, 2H), 6.98−7.06,
7.13−7.18, 7.23−7.28 (3m, 5H), 7.51 (s, 1H), 7.67 (s, 1H), 7.75−7.81
(m, 6H), 7.92−7.99 (m, 4H), 8.04−8.10 (m, 2H), 8.15 (d, 1H, J = 6.8
Hz), 8.22−8.28 (m, 8H), 8.70 (s, 2H), 8.88−8.91 (AB system, 4H, J =
5.0 Hz); 13C NMR (75 MHz, CDCl3) δ 108.8, 118.1, 118.2, 118.4,
118.7, 120.2, 121.2, 121.6, 122.1, 124.5, 125.3, 126.9, 127.0, 127.2,
127.4, 127.9, 128.1, 128.2, 128.9, 129.0, 129.3, 131.7, 133.5, 133.7,
133.8, 134.1, 134.6, 138.4, 139.3, 141.7, 142.1, 144.6, 145.2, 148.9,
164.7; HRMS (ESI-FTICR) m/z [M + H]+ calcd for C60H36N6O
857.3029, found 857.3025; UV−vis (CHCl3) λmax (log ε) 442 (5.22),
528 (4.42), 573 (4.39), 604 (4.11), 663 (3.24) nm.
Molecular Modeling. Parameters for compounds 11 and 12 were
taken from the GAFF force field29 using Antechamber,30 whereas
chloroform was described with parameters taken from Fox et al.;31
atomic RESP32,33 fitted partial charges for 11 and 12 were obtained
from HF/6-31G* level calculations using Gaussian 09.34
Simulation boxes (ca. 55 × 55 × 55 Å3 after equilibration) were
constructed from one molecule of solute (11 or 12) inside a cubic box
containing 1270 chloroform molecules. Simulations began with an
initial solvent minimization procedure for the removal of close
contacts between solute and solvent molecules, with the solute placed
under strong positional restrains. The restrains were then removed,
and the whole system was allowed to relax. Subsequently, a weak
positional restrain was applied to the solute, and the system was heated
to 300 K in the NVT ensemble for 0.5 ns, using the “velocity rescaling
with stochastic term” thermostat (τcoupling = 2.0 ps), and equilibrated
under the NPT ensemble during 1.5 ns using the Berendsen barostat
(τcoupling = 5.0 ps) until the density of the system was brought to a
plateau. The positional restraints used throughout both heating and
equilibration procedures were definitely removed during the data
collection period (100 ns in the NPT ensemble for each system). The
LINCS algorithm35 was used to constrain all hydrogen involving bond
distances at their equilibrium values; periodic boundary conditions,
along with a 12 Å nonbonded cutoff were used; long-range
electrostatic interactions were calculated with the particle mesh
Ewald (PME) method.36
1
13: H NMR (300 MHz, CDCl3) δ 7.26−7.33 (m, 2H, overlapped
with CHCl3 signal), 7.40 (s, 1H), 7.48 (s, 1H), 7.64−7.71 (m, 6H),
7.72−7.78 (m, 2H), 7.80−7.85 (m, 4H), 7.89−7.99 (m, 10H), 8.66−
8.69 (m, 4H), 8.76 (d, 1H, J = 5.0 Hz), 8.71 (d, 1H, J = 5.0 Hz); 13C
NMR (75 MHz, CDCl3): 112.5, 116.3, 116.9, 118.1, 120.1, 120.3,
121.2, 122.3, 124.9, 126.0, 127.1, 127.5, 128.0, 128.4, 129.0, 129.2,
129.9, 131.0, 132.1, 132.3, 132.7, 132.8, 132.9, 133.5, 136.3, 136.8,
140.0, 140.1, 141.4, 141.8, 141.9, 142.4, 142.5, 143.7, 144.1, 149.6,
156.9, 161.2; HRMS (ESI-FTICR) m/z [M + H]+ calcd for
C56H33N6NiO 863.2064, found 863.2052; UV−vis (CHCl3) λmax
(log ε) 453 (4.99), 554 (4.07), 595 (4.11) nm.
13a: 1H NMR (500 MHz, CDCl3) δ −2.60 (s, 2H), 7.28−7.32 (m,
2H, overlapped with the CHCl3 signal), 7.40 (s, 1H), 7.49 (s, 1H),
7.72−7.80 (m, 8H), 7.88−7.95 (m, 4H), 8.01−8.07 (m, 2H), 8.21−
8.25 (m, 8H), 8.71 (s, 2H), 8.87−8.91 (m, 4H); 13C NMR (75 MHz,
CDCl3): 112.5, 118.3, 118.8, 121.1, 121.3, 121.3, 122.8, 124.8, 126.0,
126.9, 127.9, 128.1, 128.2, 128.6, 128.8, 129.1, 129.2, 130.0, 132.0,
133.79, 133.84, 134.2, 134.3, 134.6, 141.60, 141.64, 141.7, 141.8,
141.9, 149.6, 157.1, 161.5, 164.3; HRMS (ESI-FTICR) m/z [M + H]+
calcd for C56H35N6O 807.2867, found 807.2864; UV−vis (CHCl3)
λmax (log ε) 455 (5.11), 529 (4.18), 566 (3.89), 606 (3.78), 662 (3.26)
nm.
Compounds 14 and 14a. Powdered 4Å molecular sieves (18.0
mg) were added to a solution of “phthalic” acid 4 (17.5 mg; 21.7
μmol) in 1,2,4-TCB (1.8 mL), and the mixture was stirred at reflux for
1 h. A solution of naphthalene-1,8-diamine (1.6 mg, 1 equiv) in dry
pyridine (1.8 mL) was added to the reaction mixture, which was
stirred at reflux (220 °C) for 16 h. After cooling, the reaction mixture
Calculations of ring current contributions to proton chemical (δH)
shifts were performed according to the Haigh−Mallion26 model (δH =
iBG(r), where i and B are constants characteristic of the ring and G(r)
is a structural factor describing the position of the probe proton
relative to the ring), using i = 1.0 and B = 5.455 × 10−6 Å, with a
homemade Python program.
The principal components analysis of the solute molecules, shown
in Supporting Information, was performed (for each system) as
follows: (i) the 50,000 generated conformations during the 100 ns
collection runs were fitted to the first structure of the set, in order to
remove degrees of freedom due to molecular rotation and translation;
the fit was performed through minimization of the mean square root
deviation (rmsd) between heavy atoms; (ii) the covariance matrix (in
I
dx.doi.org/10.1021/jo400948s | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Cartesian coordinates space) was calculated for the fitted set; (iii) the
eigenvectors and associated eigenvalues were then obtained upon
diagonalization of the covariance matrix. In the case of compound 11,
the first principal component (PC1) accounts for 80% of its overall
motion, whereas in compound 12 it accounts for 65%.
(18) Moura, N. M. M.; Faustino, M. A. F.; Neves, M. G. P. M. S.; Paz,
F. A. A.; Silva, A. M. S.; Tome, A. C.; Cavaleiro, J. A. S. Chem.
́
Commun. 2012, 48, 6142.
(19) Vicente, M. G. H.; Jaquinod, L.; Khoury, R. G.; Madrona, A. Y.;
Smith, K. M. Tetrahedron Lett. 1999, 40, 8763.
(20) Liu, W.; Fronczek, F. R.; Vicente, M. G. H.; Smith, K. M.
Tetrahedron Lett. 2005, 46, 7321.
(21) Silva, A. M. G.; Faustino, M. A. F.; Tome, A. C.; Neves, M. G. P.
́
M. S.; Silva, A. M. S.; Cavaleiro, J. A. S. J. Chem. Soc., Perkin Trans. 1
2001, 2752.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H, 13C, and 2D NMR spectra of compounds 2−14 and
representations of molecular mechanics/dynamics simulations
for compounds 11 and 12. This material is available free of
charge via the Internet at http://pubs.acs.org.
́
(22) Carvalho, C. M. B.; Neves, M. G. P. M. S.; Tome, A. C.; Paz, F.
A. A.; Silva, A. M. S.; Cavaleiro, J. A. S. Org. Lett. 2011, 13, 130.
(23) The low solubility of the Ni complex 12 prevented the
acquisition of a well resolved 13C NMR spectrum.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gneves@ua.pt; actome@ua.pt.
Notes
(24) Mamada, M.; Per
2011, 13, 4882.
́
ez-Bolívar, C.; Anzenbacher, P., Jr. Org. Lett.
■
(25) Zhang, Y.; Hanifi, D.; Alvarez, S.; Antonio, F.; Pun, A.;
Klivansky, L. M.; Hexemer, A.; Ma, B.; Liu, Y. Org. Lett. 2011, 13,
6528.
(26) Haigh, C. W.; Mallion, R. B. J. Chem. Phys. 1982, 76, 4063.
(27) Zonta, C.; De Lucchi, O. Eur. J. Org. Chem. 2006, 449.
(28) Luguya, R.; Jaquinod, L.; Fronczek, F. R.; Vicente, M. G. H.;
Smith, K. M. Tetrahedron 2004, 60, 2757.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Thanks are due to Fundaca
̧
o para a Cien
̃
̂
cia e a Tecnologia
(29) Wang, J. M.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case,
D. A. J. Comput. Chem. 2004, 25, 1157.
(FCT), European Union, QREN, FEDER and COMPETE for
funding the QOPNA research unit (project PEst-C/QUI/
UI0062/2011), CICECO (PEst-C/CTM/LA0011/2011), the
Project PTDC/QUI/74150/2006, and the Portuguese National
NMR Network. C.M.B.C. and S.M.S. thank FCT for their
grants SFRH/BD/38611/2007 and SFRH/BPD/64752/2009,
respectively.
(30) Wang, J. M.; Wang, W.; Kollman, P. A.; Case, D. A. J. Mol.
Graphics Modell. 2006, 25, 247.
(31) Fox, T.; Kollman, P. A. J. Phys. Chem. B 1998, 102, 8070.
(32) Bayly, C. I.; Cieplak, P.; Cornell, W. D.; Kollman, P. A. J. Phys.
Chem. 1993, 97, 10269.
(33) Cornell, W. D.; Cieplak, P.; Bayly, C. I.; Kollman, P. A. J. Am.
Chem. Soc. 1993, 115, 9620.
(34) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, Jr., J. A.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
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Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
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