SNAr Reaction Toward the Synthesis of Fluorinated Quinolino[2,3,4-at]porphyrins

Article abstract of DOI:10.1002/ejoc.202001347

An intramolecular S_NAr displacement of one o-fluorine atom of a meso-pentafluorophenyl-substituted porphyrin metal complex by a neighboring β-amino functionality generated the corresponding meso-fluorophenyl-substituted metallo-quinolino[2,3,4-at]porphyrins that are not accessible using established quinoline-annulation methodologies. The Cu(II), Ni(II), and Zn(II) complexes were thus prepared. The parent free base quinolino[2,3,4-at]porphyrin is accessible only by demetallation of the copper or zinc complexes. A strong through-space NMR-spectroscopic coupling between the remaining o-fluorine atoms on the annulated meso-aryl group and the β-hydrogen atom on the adjacent pyrrole moiety provide a clear spectroscopic signature for the annulation. Quinoline-annulation alters the optical properties significantly. On account of the presence of the β-amino functionality, all quinoline-annulated porphyrins show strong halochromic responses with Br?nsted acids and bases, the prerequisite for their potential use in chemosensing applications.

Full text of DOI:10.1002/ejoc.202001347

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: SNAr Reaction toward the Synthesis of Fluorinated
Quinolino[2,3,4-at]porphyrins
Authors: Damaris Thuita, Matthew J. Guberman-Pfeffer, and Christian
Brueckner
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202001347
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01/2020

10.1002/ejoc.202001347
European Journal of Organic Chemistry
FULL PAPER
SNAr Reaction toward the Synthesis of Fluorinated
Quinolino[2,3,4-at]porphyrins
Damaris Thuita[a], Matthew J. Guberman-Pfeffer[a,b], and Christian Brückner[a],*
Abstract: An intramolecular SNAr displacement of one o-fluorine atom
of a meso-pentafluorophenyl-substituted porphyrin metal complex by
a neighboring b-amino functionality generated the corresponding
meso-fluorophenyl-substituted metallo-quinolino[2,3,4-at]porphyrins
that are not accessible using established quinoline-annulation
methodologies. The Cu(II), Ni(II), and Zn(II) complexes were thus
prepared. The parent free base quinolino[2,3,4-at]porphyrin is
accessible only by demetallation of the copper or zinc complex. A
strong through-space NMR-spectroscopic coupling between the
remaining o-fluorine atoms on the annulated meso-aryl group and the
b-hydrogen atom on the adjacent pyrrole moiety provide a clear
spectroscopic signature for the annulation. Quinoline-annulation
alters the optical properties significantly. On account of the presence
of the b-amino functionality, all quinoline-annulated porphyrins show
strong halochromic responses with Brønsted acids and bases, the
prerequisite for their potential use in chemosensing applications.
corresponding nitrogen atom in 3 is sp2-hybridized. All possess
significantly red-shifted optical spectra.[4b, 5d, 6] Compounds 2M
were also shown to have the ability to coordinate to transition
2b, 7]
metals, as shown for its Pd(II) complex (2Ni)2Pd.[2a,
Compound 3 showed unique photoacoustic properties and a
biocompatible derivative was utilized as a photoacoustic imaging
agent in a mouse tumor model.[8]
While there are multiple ways to introduce a b-amino group, a
common feature in all quinoline-annulated systems is that the
bond between the b-nitrogen atom and the flanking meso-aryl
group was formed via harsh, thermally induced, oxidative bond
formation conditions or SEAr reactions.[2a, 2b, 2d, 4b, 5]
R1
Ph
R2
N
N
R3
N
N
Pd
Ni
N
N
N
N
N
Introduction
Ar
M
Ar
N
O
Ph
2
H
Ph
(2Ni)2Pd
The introduction of functional groups to the periphery of
porphyrins and their analogues is an attractive approach to, for
example, generate chemosensors that take advantage of their
frequently bright fluorescence emission or strong UV-vis
absorbance.[1] In this context, the introduction of amino groups is
central since they can be flexibly converted to a range of
functionalities and their inherent ability to interact with metal ions
and protons.[2] Amino groups have been introduced to a range of
positions on the porphyrin,[3] often through nitration reactions or
the synthesis of porphyrins with nitrated components.[2b, 2d, 4]
One class of b-aminoporphyrins are the quinoline-annulated
porphyrins (quinolino[2,3,4-at]porphyrins), such as 1/1M through
3/3M.[2a, 2b, 2d, 4b, 5] Compound 1 and closely related compound 2
contain an sp3-hybridized b-amino group, whereby the
Ar
M = 2H, R3 = H,
1:
1Ni: M = Ni, R3 = H
1aNi: M = Ni, Ar = Ph, R1 = R2 = R3 = H
2:
M = 2H, Ar = Ph, R1 = R2 = H, R3 = -CHO, 2
F
F
F
F
O
N
O
OH
C6F5
N
N
N
N
N
N
N
N
Ph
C6F5
M
Ph
M
M = 2H, 3
M = Ni, 3Ni
M = 2H, 4
M = Ni, 4Ni
Ph
C6F5
[a] Prof. Dr. C. Brückner, D. Thuita, Dr. M.J. Guberman-Pfeffer
Department of Chemistry
Figure 1. Literature-known quinoline-annulated porphyrins (1 through 3) and
chromene-annulated chlorin 4.
University of Connecticut, Unit 3060
Storrs, CT 06268-3060, U.S.A.
E-mail: c.bruckner@uconn.edu
Homepage: http://bruckner.research.uconn.edu
We introduced chromene-annulated chlorin
4 and related
chromophores that were formed by an SNAr displacement of an
ortho-fluorine atom of a meso-pentafluorophenyl group by a
neighboring b-hydroxy functionality under relatively mild
conditions (warming in DMF).[9] The SNAr displacement of p- and
[b] Current address:
Department of Molecular Biophysics and Biochemistry and the
Microbial Science Institute
Yale University
New Haven CT 06520, U.S.A.
o-fluorine
atoms
of
meso-pentafluorophenyl-substituted
porphyrinoids by a range of N-, O-, or S-nucleophiles is well-
known,[10] and was used to introduce solubilizing groups,[11]
Supporting information for this article is given via a link at the end of
the document.
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10.1002/ejoc.202001347
European Journal of Organic Chemistry
FULL PAPER
though the utilization of this reaction for intramolecular
annulations is relatively rare.[9, 12]
generated by nitration of meso-tetrakis(pentafluorophenyl)-
porphyrinato metal complexes,[13] but with some variations in the
particular reduction conditions used (Scheme 1).[14] The crude
b-aminoporphyrin complexes 6M were then subjected to the
intramolecular SNAr-type annulation reaction by simply heating in
acetonitrile (b.p. = 82 °C). This quantitatively converted the
starting materials within 1 h to generate a major product 7M of
lower polarity, in 50% isolated yields (over two steps). All products
showed a composition (as per ESI– HR-MS) corresponding to the
starting materials less one equivalent of HF, as expected for the
annulated target compound.
We report here an addition to the number of methods known to
form quinolino[2,3,4-at]porphyrins using an intramolecular SNAr
displacement of an o-fluorine atom of a meso-pentafluorophenyl-
substituted porphyrin by a neighboring b-amino functionality. This
method is complementary to the existing methods in that it allows
the generation of meso-pentafluorophenyl-substituted quinoline-
annulated porphyrins hitherto not accessible using the traditional
methodologies.
This reaction was only suitable for the reasonably stable
b-aminoporphyrin metal complexes 6M. The use of the
corresponding free base b-aminoporphyrin failed to provide a
major product and, instead, generated a myriad of intractable
compounds. Thus, access to the free base annulated derivative
was possible only via acid-induced demetallation of the copper or
zinc complexes, 7Cu or 7Zn, respectively.
Results and Discussion
Formation of Quinolino[2,3,4-at]porphyrins. The synthesis of
known b-aminoporphyrin complexes 6M (M = Cu(II), Ni(II), Zn(II))
proceeded as described previously via reduction of the
corresponding b-nitroporphyrin complexes 5M, themselves
F
F
F
F
H
C6F5
C6F5
NH2
NO2
N
NaBH4,
10% Pd/C, N2,
CH3CN/EtOH,
r.t.,10 min
CH3CN, 1h
Δ
N
N
N
N
N
N
N
N
N
N
N
C6F5
C6F5
C6F5
C6F5
M
M
M
N
C6F5
C6F5
C6F5
C6F5
C6F5
5M: M = Cu(II), Ni(II), Zn(II)
6M: M = Cu(II), Ni(II), Zn(II)
(not purified)
7M: M = Cu(II), Ni(II), Zn(II)
(50% isolated yields over two steps)
for 7Cu: TFA, conc. H2SO4
C6F5
F
F
F
F
N
N
N
N
H
H
C6F5
C6F5
N
H
N
N
N
N
8
H
C6F5
C6F5
C6F5
H
7H2
(88%)
C6F5
Scheme 1. Formation of title compounds 7M and 7H2 from the ultimate starting porphyrin, meso-tetrakis(pentafluorophenyl)porphyrin 8.
The facility of the intramolecular annulation reaction was already
presaged by the ESI– mass spectra of the precursor b-amino-
metalloporphyrins, as shown for the spectrum for 6Cu (Figure 2).
from the intramolecular loss of HF are not uncommon, but
frequently require more forcing tandem MS conditions.[15]
The aryl groups in meso-arylporphyrins are in idealized
Under standard MS conditions (100% CH3CN, 30 V cone voltage), perpendicular arrangements to the mean plane of the
the peak corresponding to the annulated product [M-H-HF]– is
more intense than the parent [M-H]– peak. The observation of
annulations of meso-fluoro-alkyl and -arylporphyrins resulting
porphyrin.[16] In contrast, the b-to-o-aryl bond formation forces the
meso-aryl group into much greater co-planarity with the porphyrin
ring.[17] This brings the o-fluorine atom on the annulated meso-aryl
group opposite of the annulation site into close proximity to the
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10.1002/ejoc.202001347
European Journal of Organic Chemistry
FULL PAPER
b-hydrogen atom on the adjacent pyrrole moiety. As we
discovered for chromene-annulated chlorins (like 4),[9a] this
proximity leads to a diagnostic strong coupling between these two
atoms, as seen in a strong correlation peak in the 1H-19F HOESY
spectra of the meso-fluoroaryl quinolino[2,3,4-at]porphyrins and
their diamagnetic metal complexes (as shown for 7Zn, Figure 3).
Figure 4. Computed relaxed potential energy scan relationship over the β-H–o-
F distance in 0.1 Å increments to shorter and longer lengths than the 2.31 Å
separation found in the minimum energy conformer, plotting relative energies
and 1H–19F nuclear spin-spin coupling constants (at the PBEPBE/def2-TZVP
level of theory), for the simplified model of 7Zn shown. B3LYP-D3/[SDD level of
theory for Zn and 6-31G(d) level for H, C, N, F; the conformationally little
restricted, non-annulated meso-aryl groups were omitted for simplicity; for
details, see ESI.
Figure 2. HR-MS (ESI–, 100% CH3CN, TOF) spectrum of 6Cu highlighting the
proposed origin of the [M-H-HF]– peak. The isotope patterns match those of the
compositions indicated, see ESI.
The equilibrium β-H–o-F distance was computed to be 2.31 Å at
the minimum energy point, correlating to a computed 18 Hz
coupling constant between these atoms. The experimental
coupling value for 7Zn is slightly lower, 14 Hz, suggesting that
either the computed coupling constant or the degree of
conformational distortion of the macrocycle are slightly over-
estimated. Using the computed Boltzmann-weighted average of
the coupling constants (15.6 Hz) over the thermally accessible
distances reduces the minor discrepancy down to insignficant
values. The experimental values for the nickel complex 7Ni are
11.3 Hz and for the free base 7H2 12 Hz, suggesting that the H-F
distances in these two compounds are larger than for the zinc
complex.
The computation of the model for 7Zn also suggests that the
annulation introduces a modest ruffling-type distortion to the
porphyrin macrocycle, with some minor saddling, doming and
waving contributions (see ESI). The conformation of nickel
porphyrins is, on account of the presence of the small square
planar coordinated, diamagnetic d8 nickel(II) ion, often dominated
by a strongly ruffled conformation.[18] In fact, the crystal structures
of the closely related, non-fluorinated meso-phenyl-substituted
nickel complex 1aNi (CCDC codes ERATIA and VIDRAC) show
these strongly ruffled conformations (see ESI),[2b, 2d] albeit the
distance between the β-C(H)–o-C(H) carbon atoms (of 3.07 Å) is
shorter than the corresponding computed carbon-carbon atom
distance in the model of 7Zn (3.17 Å).
Figure 3. 1H-19F HOESY (CDCl3) spectrum of 7Zn, showing the diagnostic
signal for the formation of b-to-o-aryl linkage in meso-pentafluorophenyl-derived
porphyrins in comparison to related correlations.
1
Since this H-19F correlation is diagnostic for the annulation and
might provide also a clear probe for the conformation of the
macrocycle, we performed a relaxed potential energy scan for a
1
simplified model of 7Zn (Figure 4). The distance-dependent H-
19F NMR spin coupling constant and relative energies were
determined (see computational details in the ESI).
In the previously investigated chromene-annulated chlorins,[9]
a
computed H–F distance of 2.5 Å corresponded to an experimental
coupling constant of 9.7 Hz; the value computed for this distance
we also (at 13 Hz), overestimated by the same 3-4 Hz as above,
but the general larger distance-smaller coupling constant
relationship holds.
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10.1002/ejoc.202001347
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We conclude from these analyses that while the >10 Hz β-H–o-F
coupling is a reliable indicator for the presence of an o-annulated
meso-pentafluorophenyl ring, a numerical interpretation of the
experimental coupling constant in terms of β-H–o-F distances or
even conformational modes is, in light of the small data set
available and in the absence of a thorough error analysis, as yet
tenuous.
Optical Properties of Quinolino[2,3,4-at]porphyrins. Similarly
2d]
to the non-fluorinated derivatives,[2b,
annulation leads to
significantly altered metalloporphyrin-like UV-vis spectra of the
quinolino[2,3,4-at]porphyrins 7M compared to those of the
corresponding 2-amino-porphyrins, as illustrated for the copper
complexes (Figure 5A) (see also ESI). Upon annulation, the Soret
band is markedly red-shifted (404 to 442 nm) but the longest
wavelengths of absorption (lmax) is red-shifted to a lesser degree
(599 to 622 nm). We attribute these shifts to the altered
conformation of the annulated chromophore and, to a smaller
extent, to the increased co-planarity (and associated greater π-
conjugation) of the annulated meso-aryl group. The optical
changes upon annulation of this all-sp2-hybridized porphyrinic
macrocycle are much more pronounced than upon annulation of
the chlorin precursor to 4,[9a, 19] suggesting that the conformational
changes imposed by the quinoline-annulation reaction of the
porphyrin are more extensive than upon chromene-annulation of
the chlorin.
The annulated free base 7H2 possesses a (red-shifted) porphyrin-
like UV-vis spectrum (Figure 5C). Remarkably, both the free base
7H2 (Figure 5C) and its metal complexes 7M (shown for 7Ni,
Figure 5B) show strong halochromic responses, both of which we
attribute to the presence of the C6F4-substituted b-amino
functionality. The response to strong base may set these
fluorinated derivatives apart from their non-fluorinated
2d]
congeners,[2b,
though their halochromic response was not
reported. We also note that we observe the formation of the M–
ions in the ESI mass spectra of the metallocomplexes that are
also most readily explained with the facile deprotonation of the b-
amino group.
Figure 5. UV-vis spectra of the compounds indicated in CH2Cl2 (black trace),
CH2Cl2 + 1% TFA (blue trace), and CH2Cl2 + 1% Et3N (red trace). Spectra for
7Ni and 7H2 under acidic and basic conditions in the range between 300 and
1100 nm included in the ESI.
Conclusions
We reported here the intramolecular SNAr reaction of a b-amino-
porphyrin with a flanking meso-pentafluorophenyl-group to form
quinolinometalloporphyrins in acceptable yields in two simple
steps from the corresponding meso-pentafluorophenyl-2-nitro-
metalloporphyrin. The free base is accessible via the
demetallation of the copper or zinc complexes. Clear
spectroscopic signatures for the annulation could be detected.
This method is complementary to existing methods of generating
quinoline-annulated porphyrinoids in that it allows the formation of
meso-pentafluorophenyl-substituted
systems
that
were
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10.1002/ejoc.202001347
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Quinolino[2,3,4-at]porphyrinato]Ni(II) (7Ni). Nitroporphyrin 5Ni (7.6 ×
10−5 mol, 82 mg) dissolved in CH3CN (10−15 mL) was reduced with 10%
Pd/C (0.10 g) and NaBH4 (1.0 × 10−2 mol, 390 mg) in EtOH (2−5 mL)
according to the general Step 1 procedure to produce crude 6Ni. Rf of 6Ni
= 0.38 (silica-40% hexane/CH2Cl2). Quinoline-annulated porphyrin 7Ni
was produced and isolated by chromatography (silica, 25%
hexane/CH2Cl2) as a green-coloured solid in 50% yield (3.8 × 10−5 mol, 39
unavailable along established routes that rely on oxidative
methods or SNAr reactions. This is important because meso-
pentafluorophenyl-substituted porphyrinoids were shown to be
most versatile in the generation of functionalized, water-soluble
and/or biologically active porphyrinoids.
mg) according to the general Step
2 procedure. Rf (silica−25%
hexane/CH2Cl2) = 0.88. 1H NMR (400 MHz, CDCl3, δ) 9.60 (s, 1H), 9.25
Experimental Section
3
(dd, J = 11.3, H-FJ = 5.0 Hz, 1H), 8.70 (q, 3J = 6.1 Hz, 4H), 8.64 (s, 1H),
8.13 (s, 1H) ppm. 13C NMR (101 MHz, CDCl3, δ): 147.5, 145.0, 143.0,
142.7, 142.1, 141.1, 140.2, 139.2, 138.8, 138.3, 136.4, 133.6, 133.1, 132.2,
131.85, 131.5, 130.9, 130.5, 114.6, 104.2, 102.7, 100.2, 99.3, 99.0 ppm.
19F NMR (376 MHz, CDCl3, δ): –136.08 to –137.52 (m, 6F), –137.67 (dt,
3J = 21.1, 4J = 10.4 Hz, 1F), –151.95 (q, 3J = 19.6 Hz, 3F), –154.16 (t, 3J =
20.7 Hz, 1F), –161.20 (s, 2F), –161.41 to –161.59 (m, 4F), –162.19 (dd, 3J
= 20.0, 4J = 9.8 Hz, 1F), –164.26 to –164.38 (m, 1F) ppm. UV-vis (CH2Cl2)
λmax (log ε): 425.1 (4.19), 550.9 (3.10), 619.0 (3.28) nm. FT-IR (neat,
diamond ATR): nN-H = 3436.5 cm–1. HR-MS (ESI–, 100% CH3CN, TOF):
m/z calc’d for C44H7F19N5Ni [M-H]– 1023.9757; found 1023.9792.
Materials and Instruments:
All solvents and reagents (Sigma-Aldrich, St. Louis, MO, USA and Acros,
Fair
Lawn,
NJ,
USA)
were
used
as
received.
meso-
Tetrakis(pentafluorophenyl)porphyrin was either synthesized according to
the literature procedure[20] or obtained commercially. meso-
Tetrakis(pentafluorophenyl)-2-nitro-porphyrins 5Cu, 5Ni, and 5Zn were
synthesized according to literature procedures.[13]
Aluminum-backed, silica gel 60, 250 μm thickness analytical plates were
used for analytical TLC; Either 20 ´ 20 cm, glass-backed, silica gel 60,
500 µm thickness preparative TLC plates or standard grade, 60 Å, 32-63
µm flash column silica gel were used for the chromatographic purification
of the products.
Quinolino[2,3,4-at]porphyrinato]Zn(II) (7Zn). Nitroporphyrin 5Zn (4.42 ×
10−5 mol, 48 mg) dissolved in CH3CN (10 mL) was reduced with 10% Pd/C
(0.10 g) and NaBH4 (1.0 × 10−2 mol, 390 mg) in EtOH (2−5 mL) according
to the general Step 1 procedure to produce crude known 6Zn.[21] Rf of 6Zn
= 0.22 (silica-40% hexane/CH2Cl2). Quinoline-annulated porphyrin 7Zn
was produced and isolated by chromatography (silica, 25%
hexane/CH2Cl2) a green-coloured solid in 50% yield 2.9 × 10−5 mol, 30 mg)
according to the general Step 2 procedure. Rf (silica−25% hexane/CH2Cl2)
1H and 19F NMR spectra were recorded on a Bruker 400 MHz instrument
in the solvents indicated, and were referenced to residual solvent peaks.
All UV-vis spectra were recorded on Cary 50 or 100 UV-vis spectrometers
(Varian). FT_IR spectra were recorded on a Bruker Alpha ATR instrument
with diamond window. High-resolution mass spectra were recorded from
CH3CN solutions (~10-6 M) using an AB Sciex QStar Elite Quadrupole-TOF
mass spectrometer at the Mass Spectrometry Facility, Department of
Chemistry, University of Connecticut.
= 0.42. 1H NMR (400 MHz, CDCl3, δ): 9.49 (s, 1H), 9.24 (dd, 3J = 13.7, H-F
J
= 4.2 Hz, 1H), 8.91 (dd, 3J = 7.5, 4J = 4.5 Hz, 3H), 8.85 (d, 3J = 4.5 Hz, 1H),
8.70 (d, 3J = 4.4 Hz, 1H), 8.27 (s, 1H) ppm. 13C NMR (126 MHz, CDCl3, δ):
151.0, 150.8, 150.5, 150.4, 150.1, 147.8, 147.6, 147.1, 146.0, 145.6, 143.0,
141.0, 140.0, 138.6, 137.15, 136.6, 132.4, 132.3, 132.2, 132.0, 131.8,
131.6, 131.5, 131.1, 131.0, 130.2, 130.0, 129.0, 128.7, 116.6, 105.1, 105.0,
3
99.2 ppm. 19F NMR (376 MHz, CDCl3, δ): –136.72 (s, 1F), –136.96 (d, J
Step 1: General Procedure for the Formation of 2-Aminometallo-
porphyrins (6M) via Reduction of 2-Nitrometalloporphyrins (5M).
Reduction method adopted from the literature:[14] In a 50 ml three-neck
round bottom flask equipped with a stir bar and capped with septa, a
nitrogen inlet and outlet, 10% Pd/C was stirred in ethanol (EtOH) and the
suspension was purged with dry N2. NaBH4 was dissolved in EtOH and
added slowly to the solution via syringe and the reaction mixture was kept
under an inert atmosphere using a N2-filled balloon. Nitroporphyrin 5M was
dissolved in acetonitrile (CH3CN) and solution added dropwise over ∼10
min to the reductant mixture via syringe. A noticeable color change from
magenta to deep green took place during this time. Once no starting
material could be detected by TLC, the organic phase was filtered through
a short plug of diatomaceous earth (Celite®), and the filter cake rinsed with
CH3CN. The volume of the solution was reduced by rotary evaporation and
the solution of the crude 2-aminometalloporphyrin 6M was immediately
used as is for the annulation step.
3
3
= 17.4 Hz, 4F), –137.22 (dd, J = 23.5, 4J = 6.9 Hz, 2F), –152.58 (q, J =
22.4 Hz, 3F), –155.02 (t, 3J = 20.6 Hz, 1F), -161.71 (td, 3J = 22.3, 4J = 6.6
Hz, 2F), –161.99 to –162.15 (m, 4F), -163.29 (d, 3J = 11.9 Hz, 1F), –165.04
(t, 3J = 21.4 Hz, 1F) ppm. UV-vis (CH2Cl2): λmax (log ε) 407.1 (5.18), 441.9
(5.42), 561.0 (4.31), 603.0 (4.30), 627.9 (4.57) nm. FT-IR (neat, diamond
ATR): nN-H = 3414.4 cm–1. HR-MS (ESI–, 100% CH3CN, TOF): m/z calc’d.
for C46H12F19N5O65Zn– [M-H]– 1075.9852; found 1075.9836; C44H7F19N5Zn
[M-H]– 1029.9696; found 1029.9753.
Quinolino[2,3,4-at]porphyrinato]Cu(II) (7Cu). Nitroporphyrin 5Cu (9.10
× 10−5 mol, 98 mg) dissolved in CH3CN (10 mL) was reduced with 10%
Pd/C (0.10 g) and NaBH4 (1.0 × 10−2 mol, 390 mg) in EtOH (4 mL)
according to the general Step 1 procedure to produce crude known
6Cu.[13b] Rf of 6Cu
= 0.58 (silica-50% hexane/CH2Cl2). Quinoline-
annulated porphyrin 7Cu was produced and isolated by chromatography
(silica, 25% hexane/CH2Cl2) as a green-coloured solid in 50% yield (4.6 ×
10−5 mol, 47 mg) according to the general Step 2 procedure. Rf (silica−50%
hexane/CH2Cl2) = 0.30. UV-vis (CH2Cl2) λmax (log ε): 403.0 (4.80), 442.0
Step 2: General Procedure for the Annulation of 2-Aminometallo-
porphyrins (6M). The crude product from Step 1 was diluted with CH3CN
(to 25 ml) and transferred to a 50 ml round-bottom flask equipped with stir
bar and condenser. The reaction mixture was stirred and heated to reflux.
The reaction monitored by TLC. Upon consumption of the starting material
after ~1 h, the reaction was allowed to cool to ambient temperature and
diluted with CH2Cl2 (25 ml). The reaction mixture was transferred into a
separatory funnel, the solution was washed with water (25 ml), dried over
anhyd. Na2SO4, and evaporated to dryness using rotary evaporation. The
residue was purified by flash column or preparative plate chromatography.
(5.06), 554.9 (3.96), 622.0 (4.17) nm. FT-IR (neat, diamond ATR): nN-H
3415.3 cm–1 HR-MS (ESI–, 100% CH3CN, TOF): m/z calc’d for
C44H7CuF19N5 [M-H]– 1028.9700; found 1028.9856.
=
.
Quinolino[2,3,4-at]porphyrin (7H2). In a 25 ml round-bottom flask, crude
[quinolinoporphyrinato]Cu(II) (7Cu) (prepared from 9.10 × 10−5 mol 5Cu)
was dissolved in trifluoracetic acid (CF3CO2H, 2–4 ml). Concentrated
H2SO4 (2 mL) was then added dropwise to the solution. Alternatively,
crude [quinolinoporphyrinato]Zn(II) (7Zn) (prepared from 4.42 × 10−5 mol
5Zn) was dissolved in CF3CO2H (2–4 ml) and chloroform (CHCl3, 5 ml).
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10.1002/ejoc.202001347
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Concentrated HCl (2 mL) was then added dropwise to the solution. The
reactions were stirred at room temperature for ~1.5 h after which the
mixture was poured onto water (100 mL). The water phase was extracted
with CH2Cl2 (5 × 5 mL). The combined organic layers were washed with
water (2 × 25 mL) and dried over anhydrous Na2CO3 and evaporated to
dryness by a rotary evaporation. The residue was purified by flash column
or preparative plate chromatography (silica, 50% hexane/CH2Cl2) to
produce 7H2 as a dark brown-coloured solid in 88% yield (77 mg, 7.97 ×
10−5 mol). Rf (silica−25% hexane/CH2Cl2) = 0.75. 1H NMR (400 MHz,
CDCl3, δ): 9.95 (s, 1H), 9.43 (dd, 3J = 4.4, H-FJ = 12 Hz, 1H), 8.96 (s, 2H),
8.78 (t, J = 4.9 Hz, 2H), 8.71 (d, J = 4.8 Hz, 1H), 8.36 (s, 1H), –1.85 (s,
2H) ppm. 13C NMR (126 MHz, CDCl3, δ): 147.5, 145.6, 143.3, 141.3,
137.5, 136.6, 132.4, 130.0, 128.2. 19F NMR (376 MHz, CDCl3, δ): –135.85
(dd, 3J = 21.5, 4J = 9.7 Hz, 1F), –136.59 (dd, 3J = 23.6, 4J = 7.9 Hz, 4F), –
136.87 (dd, 3J = 23.5, 4J = 7.9 Hz, 2F), –151.75 to –152.04 (m, 3F), –
154.35 (t, 3J = 20.3 Hz, 1F), –161.31 (td, 3J = 22.1, 4J = 7.0 Hz, 2F), –
161.64 (qd, 3J = 21.6, 4J = 6.5 Hz, 4F), –162.92 (s, 1F), –164.65 to –164.76
(m, 1F) ppm. UV-vis (CH2Cl2) λmax (log ε): 412.0 (6.40), 414.5 (6.39), 536.5
(5.35), 575.0 (5.24), 603.0 (5.15), 657.5 (5.09) nm. FT-IR (neat, diamond
ATR): nN-H = 3426 cm–1. HR-MS (ESI-, 100% CH3CN, TOF): m/z calc’d for
C44H9F19N5- [M–H]– 968.0560; found 968.0663.
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Acknowledgments
Funding for this work was provided by the U.S. National Science
Foundation (NSF) through grant CHE-1800361 and the UConn
Vice President for Research through the Research Excellence
Program. We thank Hayley Piepho and Bionca Feagin for
preliminary experiments.
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Keywords: Porphyrinoids • SNAr Reaction • b-Aminoporphyrin •
Annulation reaction
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Entry for the Table of Contents (Please choose one layout)
FULL PAPER
Porphyrin Modification*
F
F
F
Damaris Thuita, Matthew J. Guberman-
Pfeffer, and Christian Brückner*
H
C6F5
NO2
F
N
N
N
N
M
N
N
N
N
Page No. – Page No.
2 steps
C6F5
C6F5
C6F5
M
C6F5
N
SNAr Reaction Toward the Synthesis
of Fluorinated Quinolino[2,3,4-
at]porphyrins
Text for Table of Contents (about 350 characters)
C6F5
C6F5
An intramolecular SNAr displacement reaction of an o-fluorine atom on a meso-pentafluorophenyl group by the b-amino-group in
meso-tetrakis(pentafluorophenyl)-2-amino-metalloporphyrin (M = Cu(II), Ni(II), Zn(II)) provides a novel pathway toward quinoline-
annulated metalloporphyrins. The corresponding free base chromophore is available by demetallation.
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