An approach to pyrazoline-fused chlorins by dipolar [3 + 2]-cycloaddition of iminonitriles to Meso-Tetrakis(pentafluorophenyl)porphyrin: Synthesis of new PDT photosensitizers

Article abstract of DOI:10.1246/bcsj.20110408

Meso-Tetrakis(pentafluorophenyl)porphyrin reacts at higher temperature with unstable iminonitriles (RC≡N⁺-N^--Ar), affording pyrazoline-fused chlorins, according to dipolar [3 + 2]-cycloaddition pathway. The respective iminonitriles were in situ generated from the corresponding functionalized α-halogenohydrazine derivatives by 1,3-elimination of HX in the presence of base (NEt₃, DABCO). This method allows synthesis of very attractive moieties which may be of potential use as sensitizers in photodynamic therapy (PDT).

Full text of DOI:10.1246/bcsj.20110408

© 2012 The Chemical Society of Japan
Bull. Chem. Soc. Jpn. Vol. 85, No. 10, 1167-1174 (2012) 1167
An Approach to Pyrazoline-Fused Chlorins by Dipolar [3 + 2]-Cyclo-
addition of Iminonitriles to meso-Tetrakis(pentafluorophenyl)porphyrin:
Synthesis of New PDT Photosensitizers
Przemysław Wyrębek and Stanisław Ostrowski*
Institute of Chemistry, Uniwersytet Przyrodniczo-Humanistyczny w Siedlcach (formerly University of Podlasie),
ul. 3 Maja 54, 08-110 Siedlce, Poland
Received December 31, 2011; E-mail: stan@uph.edu.pl
¹
meso-Tetrakis(pentafluorophenyl)porphyrin reacts at higher temperature with unstable iminonitriles (R-C¸N+-N -
Ar), affording pyrazoline-fused chlorins, according to dipolar [3 + 2]-cycloaddition pathway. The respective iminonitriles
were in situ generated from the corresponding functionalized ¡-halogenohydrazine derivatives by 1,3-elimination of HX
in the presence of base (NEt3, DABCO). This method allows synthesis of very attractive moieties which may be of
potential use as sensitizers in photodynamic therapy (PDT).
[3 + 2]-Cycloaddition is a useful tool in the modification
of porphyrin skeleton and it has been well documented in the
recent literature in research articles, as well as in reviews.1-27
Reactions of 1,3-dipoles such as azomethine ylides,3-14 diazo-
alkanes,15-17 nitrones,18-20 nitrile N-oxides,21-26 or carbonyl
ylides27 with porphyrin derivatives gave the expected [3 + 2]-
cycloadducts. These products are very attractive chlorins and
bacteriochlorins which are sought as photosensitizers in photo-
dynamic cancer therapy (PDT).28-30
PDT is currently evaluated in multiple clinical trials with
promising results.31-34 It is a simple and relatively new
technique based on the administration of tumor-localizing
photosensitizers. They are subsequently activated by visible
light to destroy cancer cells, however their mode of action is
still not clear.
R
C6F5H
C6F5
N
N
H
Ar
NH
N
NH
N
N
N
C6F5
C6F5
F5C6
F5C6
HN
HN
C6F5
C6F5
Scheme 1.
also serve as 1,3-dipoles in this methodology. They are usually
generated in situ from ¡-halogenohydrazine derivatives 4
by 1,3-elimination of HX.37 The desired precursors 4 were
obtained according to Scheme 2.
The clinical use of PDT requires the presence of a photo-
sensitizing agent, oxygen, and light of a specific wavelength,
which matches the absorption characteristic of the photo-
sensitizer. This is a first step in the process leading to the
formation of toxic, short-lived species of oxygen (singlet 1O2),
which is thought to mediate cellular death.35
Iminonitriles could be also used as substrates in [3 + 2]-
cycloaddition to porphyrins, thus affording very attractive
pyrazoline-fused chlorins. In the recent past, Cavaleiro and
co-workers have published a paper36 concerning synthesis of
the above compounds, however the yields of the respective
products were very low. At the same time we were in the midst
of our investigations focused on the preparation of such
chlorins (Scheme 1). The results of these studies are presented
in this paper.
Iminonitriles 5 are very unstable and they readily enter into
dimerization.37-39 Thus, they were generated in situ in the
presence of dipolarophile (porphyrin, in this case). As a por-
phyrin partner for these reactions the highly active meso-
tetrakis(pentafluorophenyl)porphyrin (6) was selected, because
the bulk of porphyrins (bearing vinyl-like double bonds) are
dipolarophiles of moderate reactivity.
In the first experiment porphyrin 6 was preheated in boiling
toluene with 2-(chloro(phenyl)methylene)-1-phenylhydrazine
(4a) in the presence of NEt3 (Scheme 3). To supplement the
loss of the formed in situ iminonitrile new portions of precursor
4a and NEt3 were added every 9 h (the mixture was heated for
about 45 h). The desired chlorin 7a was formed in 29% yield
(yield for converted 6: 41%; 30% of the starting porphyrin
was recovered). Additionally, we isolated some amounts of by-
product 8a (12%). Its molecular mass Mr = 1168 determined
by MS (FD) is identical to Mr of chlorin 7a. The structure of
Results and Discussion
1
Synthesis of Chlorins. Many chlorins and bacteriochlorins
that may be of potential use as sensitizers in PDT were
synthesized by [3 + 2]-cycloaddition. As it was mentioned
above little use has been made of iminonitriles, which could
this compound was proposed on the basis of H NMR spec-
trum. At ¤ = 8.96 we found the diagnostic singlet originating
from ¢-proton of monosubstituted pyrrole ring. Another singlet
(¤ = 7.55) is probably a signal of NH-proton. This compound
Published on the web October 15, 2012; doi:10.1246/bcsj.20110408

1168 Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012)
Synthesis of New PDT Photosensitizers: Pyrazoline-Fused Chlorins
R'
C6F5
R'
O
H
H
N
N
O
(i) or (ii)
(iii)
H2N
R
N
+
H
NH
N
N
R
Cl
R
R"
R"
C6F5
F5C6
1
2
3
HN
R'
Cl
H
C6F5
N
N
(i): NEt3 / Et2O, 0°C
(ii): pyridine / ethyl acetate, reflux
(iii): PCl5 / Et2O, reflux to r.t., 16 h
6
R"
4
R'
+
–
base
solvent, Δt;
protected with CaCl2 tube
R'
R'
C
N
N
4
R
R"
+
–
–
+
base
C
N
N
C
N
N
R
R"
R
R"
4
(-HCl)
5
R'
R"
5
H
N
R
C6F5H
R
C6F5
N
a: R = C6H5, R',R" = H; b: R = p-CH3C6H4, R',R" = H;
R'
N
c: R = p-CH3OC6H4, R',R" = H; d: R = p-CH3C6H4, R' = C2H5, R" = H;
e: R = p-CH3OC6H4, R' = C2H5, R" = H; f: R = C6H5, R' = H, R" = NO2;
g: R = CH3, R' = NO2, R" = NO2; h: R = C6H5, R' = NO2, R" = NO2
N
H
NH
N
NH
N
N
N
R"
C6F5
C6F5
F5C6
F5C6
+
HN
HN
Scheme 2.
C6F5
C6F5
may be an effect of ring-opening reaction of chlorin 7a or could
be a product of electrophilic substitution at the ¢-position in
porphyrin 6 with iminonitrile. One of the mesomeric structures
of the latter possesses positive charge localized at the carbon
atom (Schemes 1 and 2). Its participation should be consid-
erable thus allowing electrophilic attack.
By this method we synthesized several pyrazoline-fused
chlorins 7a-7e. Most of the reactions were carried out in
boiling toluene for 20 h. Manipulation in conditions (reaction
time, solvent) gave, in some cases, better results. For example,
the reaction carried out in boiling cyclooctane (NEt3, precursor
4a) allowed us to effectively shorten the reaction time, and
the yield was even higher (29%, Entry 3). When NEt3 was
exchanged for DABCO, the yield of 7a was similar (ca. 25%,
Entry 4) as compared to the NEt3/toluene system. But in the
case of chlorin 7b the yield was higher, 32% (60% for
converted substrate). However, the more important herein was
shortening of the reaction time (from 20/45 to 6 h).
7
8
a: R = C6H5, R',R" = H
b: R = p-CH3C6H4, R',R" = H
c: R = p-CH3OC6H4, R',R" = H h: R = C6H5, R' = NO2, R" = NO2
d: R = p-CH3C6H4, R' = C2H5, R" = H
f: R = C6H5, R' = H, R" = NO2
g: R = CH3, R' = NO2, R" = NO2
e: R = p-CH3OC6H4, R' = C2H5, R" = H
Scheme 3.
+
+
–
–
C
N
N
C
N
N
NO2
R
NO2
R
R'
R'
5f-h
Figure 1.
In the case of ortho-substituted N-aryl rings (R¤ = Et), the
yield dramatically decreased, probably due to steric hindrance
caused by this group. In consequence, the product of electro-
philic substitution prevailed, and it was formed in good yield
(8d, 43%; 8e, 32%).
On the other hand, the reaction is very sensitive to electronic
effects. Nitro-substitution in N-aryl ring (ortho- or para-
position), suppresses effectively this process. The NO2 group as
a very strong electron-withdrawing substituent, considerably
decreasing the negative charge at nitrogen atom (see resonance
structure in Figure 1), makes the system unreactive. Thus, none
of the product was formed. It is worth mentioning that the
positive charge on carbon atom could be decreased by the
resonance effect of OCH3 group occupying the para-position
in R-aryl substituents. However, we practically did not observe
this effect (compare Entries 2 and 7).
In some reactions, e.g., 6 with 4a, traces of product that
was formed due to double (cyclo)addition of iminonitrile 5a to
porphyrin were observed (by MS spectrometry; m/z = 1363,
[M + H]+). It must be a product in which the additional moiety
is incorporated outside the porphyrin ring. We deduced this
from the 1H NMR chemical shift of NH protons in the core ring
(¤ = ¹3.57). These data are characteristic for unchanged 22³-
electron porphyrin system. Thus, we proposed for this product
structure of dihydro-1,2,4-triazole derivative 9a as an result
of [3 + 2]-cycloaddition reaction to imine bond of compound
8a (Scheme 4).
Spectroscopic Confirmation of the Structures. All the
structures of chlorins 7a-7e were easily elucidated on the basis
1
of H NMR, UV-vis, and MS spectra. For example in com-
pound 7a signals of H¢ protons of pyrrole rings neighboring

P. Wyrębek et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012) 1169
H
(D)H
N
N
N
N
H
C6F5
+
–
C6F5
C6F5
N
N
C
N
N
NH
N
N
NH
N
N
NH
N
N
5a
C6F5
F5C6
C6F5
F5C6
C6F5
F5C6
toluene, Δt,
protected with CaCl2 tube
HN
HN
HN
Ph
H
N
Ph
C6F5
C6F5
C6F5
N
Ph
N
C6F5
N
8a
8b
10b
Ph
NH
N
Figure 3.
C6F5
F5C6
HN
N
C6F5
9a
Scheme 4.
Figure 4. HSQC spectrum of compound 8b.
inside the core ring (¤ = ¹2.76) also underwent the hydrogen-
deuterium exchange.
Additionally, we recorded for this product a two-dimen-
1
sional HSQC spectrum from which one-bond correlations H-
Wavelength/nm
13C are observed. For compound 10b we could expect five
aromatic correlations (Ph and Tol rings; in the region ¤ =
6.0-8.0) and one additional at ¤ = 7.55 (in this case, postulated
=CH). While in the spectrum recorded we found only five
correlations (¤ = 7.43/125.2 (Tol); 7.18/128.9 (Ph); 7.06/
128.9 (Tol); 6.89/113.2 (Ph); 6.83/120.3 (Ph). The proton at
¤ = 7.55 does not correlate with any carbon atom. Thus, it must
be NH proton, as we anticipated earlier, and the structure of
compound is 8b. The spectrum is shown in Figure 4.
Figure 2. UV-vis spectrum of chlorin 7a.
the chlorin ring were found as four doublets [¤ = 8.68, 8.31
(J = 5.0 Hz); and ¤ = 8.64, 8.24 (J = 5.0 Hz)]. The two
remaining ¢-protons from the five-membered ring opposite
to chlorin junction appeared as an AB system (¤ = 8.49 and
8.48, J = 5.0 Hz). Finally, the diagnostic chlorin protons were
observed as two doublets (¤ = 7.51 and 6.60, J = 8.5 Hz).
Two-dimensional COSY spectrum also confirms the structure.
The above NMR pattern is typical for all the synthesized
pyrazoline-fused chlorins.
In the UV-vis spectrum the last Q-band reveals character-
istic absorption enhancement as it is expected for chlorins (for
7a: -max = 657 nm, log ¾ = 4.41; Figure 2). Such properties
are sought for PDT therapy.
Also, to confirm structures 8a-8e, additional 1H NMR
spectra were recorded (for selected product 8b, Figure 3).
Addition of D2O to NMR sample of 8b during NMR mea-
surement allowed us to observe fast hydrogen-deuterium
exchange (for signal ¤ = 7.55). This is expected for NH proton
in the above compound 8b, while rather not for vinylic =CH
proton in another possible isomer 10b, which could be a
product of ring-opening reaction. Thus, the latter structure was
definitively rejected. In this NMR experiment the NH protons
Conclusion
We presented herein an approach to fused pyrazoline-type
chlorins by dipolar [3 + 2]-cycloaddition of unstable iminoni-
triles to meso-tetrakis(pentafluorophenyl)porphyrin. Synthesis
this type of compounds is of significant importance because
the products obtained are potentially attractive and versatile
intermediates for the further derivatization of meso-arylchlorins
designed as second generation photosensitizers28 in PDT. They
exhibit properties similar to isoxazoline-fused chlorins,21-26
however their last Q-bands (in UV-vis spectrum) reveal much
stronger absorption of the light (-max µ 660 nm; Figure 2) as
compared to the latters. Additionally, the fused pyrazoline ring
conceivably may be easily cleaved40 to polar functionalities.
Such chlorins are sought and could be practically applied as
photosensitizers in antitumor PDT because in their structures
all the desired properties are deposited: they absorb low-energy

1170 Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012)
Synthesis of New PDT Photosensitizers: Pyrazoline-Fused Chlorins
UV-vis light, and subsequently may be easily converted to
soluble in physiological milieu moieties.
3H, CH2CH3). 13C NMR (CDCl3, 100 MHz): ¤ 167.6 (C=O),
145.3, 142.6, 129.4, 129.3, 129.2, 128.3, 127.1, 126.7, 121.2,
112.4, 23.5, 21.4, 13.2. Elemental Anal. Found: C, 73.09; H,
7.23; N, 10.56%. Calcd for C16H18N2O1¢1/2H2O: C, 72.98; H,
7.27; N, 10.64%.
Experimental
General. NMR spectra were recorded with a Varian MR-
1
400 spectrometer operating at 400 MHz for H and 100 MHz
N¤-(2-Ethylphenyl)-4-methoxybenzhydrazide (3e): Mp
for 13C. Coupling constants J are expressed in hertz (Hz).
Mass spectra were measured with a MARINER (ESI-TOF)
PerSeptive Biosystems spectrometer (ESI method) and GCT
Premier (FD-TOF) Waters spectrometer (FD method); m/z
intensity values for peaks are given as % of relative intensity.
UV-vis spectra were measured with a Beckman DU-68
spectrometer. TLC analysis was performed on aluminium foil
plates precoated with silica gel (60F 254, Merck); the products
have lower Rf values as compared to the starting porphyrin
6 (TLC: CHCl3). The products synthesized were isolated by
column chromatography (silica gel, 230-400 mesh; Merck
AG). Analytically pure samples were obtained via repeated
chromatography on preparative TLC plates.
155-156 °C (MeOH). H NMR (CDCl3, 400 MHz): ¤ 8.11 (s,
1
1H, NH), 7.79 (d, J = 8.4 Hz, 2H, H-ArOMe), 7.16-7.06 (m,
2H, H-Ar(Et)), 6.95 (d, J = 7.9 Hz, 1H, H-Ar(Et)), 6.93-6.85
(m, 3H, 2H of H-ArOMe and 1H of H-Ar(Et)), 6.39 (s, 1H,
NH), 3.85 (s, 3H, OCH3), 2.65 (q, J = 7.3 Hz, 2H, CH2CH3),
1.30 (t, J = 7.3 Hz, 3H, CH2CH3). 13C NMR (CDCl3, 100
MHz): ¤ 167.2 (C=O), 162.7, 145.4, 129.2, 129.0, 128.3,
126.7, 124.5, 121.2, 113.9, 112.5, 55.4, 23.6, 13.2. Elemental
Anal. Found: C, 69.94; H, 6.73; N, 10.03%. Calcd for
C16H18N2O2¢1/4H2O: C, 69.92; H, 6.78; N, 10.19%.
Synthesis of N-Phenylbenzohydrazonyl Chloride Deriv-
atives.
Derivatives 4a-4h were obtained according to
modified procedure described in the previous literature:41 To
a stirred solution (or suspension) of hydrazide 3a-3h (20.0
mmol) in a dry diethyl ether (15 mL), PCl5 (5.0 g, 24.0 mmol)
was added dropwise over a period of ca. 15 min. The reaction
mixture was heated in reflux for 1 h, then it was cooled to
room temperature and continued for the next 15 h. A solution
of phenol (5.0 g, 53.0 mmol) in diethyl ether (5 mL) was
added and after 15 min methanol (15 mL) was carefully added
dropwise.
Molecular formulas of the compounds were confirmed by
elemental analysis, HR-MS (ESI and FD) and by comparing
the isotope molecular patterns (theoretical and experimental).
Melting points are uncorrected.
All the phenylhydrazine derivatives and carboxylic acid
chlorides used were commercial products.
Synthesis of N¤-Phenylbenzhydrazide Derivatives. Hy-
drazides 3a-3c and 3f-3h were synthesized according to pro-
1
cedures described in the previous papers.41,42 Their H NMR
Isolation of Benzohydrazonyl Chlorides 4a-4e.
The
spectra and melting points were in agreement with those
reported earlier in the literature: N¤-phenylbenzhydrazide (3a);42
N¤-phenyl-4-methylbenzhydrazide (3b);43,44 N¤-phenyl-4-me-
thoxybenzhydrazide (3c);43,44 N¤-(4-nitrophenyl)benzhydrazide
(3f);41,45 N¤-(2,4-dinitrophenyl)acetohydrazide (3g);46,47 N¤-
(2,4-dinitrophenyl)benzhydrazide (3h).48,49 In a case of com-
pound 3b the additional data are given here for more detailed
and accurate characterization of the product.
reaction mixture was poured into 100 mL of water and the
product was extracted with chloroform (3 © 25 mL). The
combined organic layers were washed with water (ca. 50 mL)
and dried over anhydrous MgSO4. After evaporating the
solvent the products were isolated by column chromatography
(eluent: CHCl3/n-hexane, 1:1 for 4a; CHCl3 for 4b-4e).
Isolation of Benzohydrazonyl Chlorides 4f-4h.
The
precipitate was filtered on a Büchner funnel, washed several
times with cold water and recrystallized from methanol/
acetone mixture.
The analytically pure products were obtained: 4a,42,50 2.72 g
(59%); 4b,51,52 2.26 g (46%); 4c,52 1.57 g (30%); 4d, 1.59 g
(29%); 4e, 2.33 g (40%); 4f,53 2.17 g (39%); 4g,54 2.08 g (40%);
4h,48,54 5.60 g (87%).
In cases of new compounds and known compounds but
characterized partially in the earlier literature the additional
data are given below for more detailed and accurate character-
ization of these intermediates.
N¤-Phenyl-4-methylbenzhydrazide (3b):
Known com-
pound; mp 168-169 °C (MeOH), lit.44 167-168 °C. 13C NMR
(CDCl3, 100 MHz): ¤ 167.7 (C=O), 148.1, 142.7, 129.4, 129.3,
129.1, 127.1, 121.3, 113.8, 21.5 (CH3).
N¤-(2-Ethylphenyl)-4-methylbenzhydrazide (3d) and N¤-
(2-Ethylphenyl)-4-methoxybenzhydrazide (3e). To a stirred
suspension of 2-ethylphenylhydrazine hydrochloride (2d ©
HCl; 3.80 g, 22.0 mmol) in diethyl ether (50 mL), NEt3 (7.7 mL,
55.2 mmol) was added dropwise. The reaction mixture was
stirred at 0 °C over 2 h, then the solution of carboxylic acid
chloride (1b or 1c, 20.0 mmol) in diethyl ether (10 mL) was
added dropwise. After 30 min of stirring the precipitate was
filtered on a Büchner funnel, washed with cold water, and
recrystallized from methanol to give the desired product: N¤-(2-
ethylphenyl)-4-methylbenzhydrazide (3d), 3.51 g (69%) or N¤-
(2-ethylphenyl)-4-methoxybenzhydrazide (3e), 3.68 g (68%).
N-Phenyl-4-methylbenzohydrazonyl
Chloride
(4b):
Known compound; mp 134-135 °C (CHCl3), lit.51 136-
1
137 °C. H NMR (CDCl3, 400 MHz): ¤ 8.00 (s, 1H, NH), 7.83
(apparent d, J = 8.2 Hz, 2H, H-Tol), 7.32 (apparent t, J =
7.9 Hz, 2H, H-Ph), 7.24-7.16 (m, 4H, 2H of H-Tol and 2H of
H-Ph), 6.95 (apparent t, J = 7.3 Hz, 1H, H-Ph), 2.40 (s, 3H,
CH3-Tol).
N¤-(2-Ethylphenyl)-4-methylbenzhydrazide (3d):
Mp
169-170 °C (MeOH). 1H NMR (CDCl3, 400 MHz): ¤ 8.32
(s, 1H, NH), 7.71 (d, J = 7.8 Hz, 2H, H-Tol), 7.20 (d, J =
7.8 Hz, 2H, H-Tol), 7.15-7.05 (m, 2H, H-Ar(Et)), 6.94 (appar-
ent d, J = 8.0 Hz, 1H, H-Ar(Et)), 6.89 (apparent t, J = 7.4 Hz,
1H, H-Ar(Et)), 6.44-6.35 (m, 1H, NH), 2.64 (q, J = 7.5 Hz,
2H, CH2CH3), 2.40 (s, 3H, CH3-Tol), 1.29 (t, J = 7.5 Hz,
N-Phenyl-4-methoxybenzohydrazonyl Chloride (4c):
Known compound; mp 130-131 °C (Et2O), lit.52 126-128 °C.
1H NMR (CDCl3, 400 MHz): ¤ 7.96 (s, 1H, NH), 7.88 (appar-
ent d, J = 8.8 Hz, 2H, H-ArOMe), 7.33 (apparent t, J = 7.8 Hz,
2H, H-Ph), 7.19 (apparent d, J = 8.0 Hz, 2H, H-Ph), 7.00-6.91
(m, 3H, 2H of H-ArOMe and 1H of H-Ph), 3.86 (s, 3H, OCH3).

P. Wyrębek et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012) 1171
Products and Yields/%a)
Table 1. [3 + 2]-Cycloaddition Reaction of Porphyrin 6 with Iminonitriles
Iminonitrile precursor
Conditions
1
2
3
4
5
6
7
8
9
10
11
12
13
4a
4a
4a
4a
4b
4b
4c
4d
4d
4e
4f
NEt3, toluene, reflux, 45 h
NEt3, toluene, reflux, 20 h
NEt3, cyclooctane, 150 °C, 8 h
7a, 29 (41); 8a, ca. 12 (17)
7a, 23 (31); 8a, 12 (16)
7a, 29 (40); 8a, 8 (11)
7a, ca. 25 (60); 8a, 10 (24)
7b, 23 (27); 8b, 15 (18)
7b, 32 (60); 8b, 5 (9)
7c, 19; 8c, 12
7d, 7; 8d, 43
DABCO, cyclooctane, 150 °C, 6 h
NEt3, toluene, reflux, 20 h
DABCO, cyclooctane, 150 °C, 6 h
NEt3, toluene, reflux, 20 h
NEt3, toluene, reflux, 20 h
NEt3, cyclooctane, 150 °C, 8 h
NEt3, toluene, reflux, 20 h
NEt3, toluene, reflux, 20 h
NEt3, toluene, reflux, 20 h
NEt3, toluene, reflux, 20 h
7d, 7 (16); 8d, 10 (23)
7e, 3 (5); 8e, 32 (52)
®
4g
4h
®
®
a) In brackets: yields for the recovered substrate.
N-(2-Ethylphenyl)-4-methylbenzohydrazonyl Chloride
(4d): Mp 46-47 °C (CHCl3). H NMR (CDCl3, 400 MHz): ¤
transferred quantitatively to a separatory funnel filled with
100 mL of water. The product was extracted with chloroform
(4 © 25 mL). The combined organic layers were washed with
brine (100 mL) and dried over anhydrous MgSO4. After
evaporating the solvent the products were isolated by column
chromatography (eluent: CHCl3/n-hexane, 1:1). Yields: chlorin
7a 34.0 mg, 29% (41% for converted 6); porphyrin 8a
contaminated with 9a 13.9 mg, ca. 12%. Additionally, 29.6
mg of substrate 6 was recovered (30%).
Procedure B: A solution of meso-tetrakis(pentafluorophen-
yl)porphyrin (6; 97.5 mg, 0.100 mmol), iminonitrile precursor
4a-4h (0.40 mmol), and NEt3 (61 mg, 0.60 mmol) in a dry
toluene (3 mL) was heated at reflux in a flask equipped with a
reflux condenser protected at the top with a CaCl2 tube over a
period of ca. 20 h. The new portions of precursor 4 (0.40 mmol)
and NEt3 (61 mg, 0.60 mmol) were added via microsyringe
(septum) every 5 h (3 times). The reaction mixture was cooled
to room temperature and transferred quantitatively to a sepa-
ratory funnel filled with 100 mL of water. The product was
extracted with chloroform (4 © 25 mL). The combined organic
layers were washed with brine (100 mL) and dried over
anhydrous MgSO4. After evaporating the solvent the products
were isolated by column chromatography (eluent: CHCl3/
n-hexane, from 1:1 to 2:1). Yields: chlorin 7a 27 mg, 23%
(31% for converted 6) and porphyrin 8a 14 mg, 12% (16%);
chlorin 7b 27 mg, 23% (27%) and porphyrin 8b 18 mg, 15%
(18%); chlorin 7c 23 mg, 19%, and porphyrin 8c 14 mg, 12%;
chlorin 7d 9 mg, 7%, and porphyrin 8d 52 mg, 43%; chlorin 7e
4 mg, 3% (5%) and porphyrin 8e 39 mg, 32% (52%).
1
8.08 (s, 1H, NH), 7.87 (apparent d, J = 8.2 Hz, 2H, H-Tol),
7.60 (d, J = 8.1 Hz, 1H, H-Ar(Et)), 7.31-7.22 (m, 3H, 2H of H-
Tol and 1H of H-Ar(Et)), 7.19 (d, J = 7.4 Hz, 1H, H-Ar(Et)),
6.96 (apparent td, J = 7.4, 0.8 Hz, 1H, H-Ar(Et)), 2.70 (q, J =
7.5 Hz, 2H, CH2CH3), 2.43 (s, 3H, CH3-Tol), 1.37 (t, J =
7.5 Hz, 3H, CH2CH3). 13C NMR (CDCl3, 100 MHz): ¤ 140.7,
139.4, 131.8, 129.1, 128.4, 127.2, 126.9, 126.4, 125.6, 120.8,
113.5, 23.7, 21.2, 13.2. Elemental Anal. Found: C, 70.49; H,
6.35; N, 10.32; Cl, 12.96%. Calcd for C16H17Cl1N2: C, 70.45;
H, 6.28; N, 10.27; Cl, 13.00%.
N-(2-Ethylphenyl)-4-methoxybenzohydrazonyl Chloride
1
(4e): Mp 44-45 °C (CHCl3). H NMR (CDCl3, 400 MHz): ¤
7.99 (s, 1H, NH), 7.91-7.85 (part of AA¤XX¤, 2H, H-ArOMe),
7.54 (d, J = 8.0 Hz, 1H, H-Ar(Et)), 7.23 (apparent t, J = 7.7
Hz, 1H, H-Ar(Et)), 7.15 (d, J = 7.4 Hz, 1H, H-Ar(Et)), 6.96-
6.88 (m, 3H, 2H of H-ArOMe and 1H of H-Ar(Et)), 3.86 (s,
3H, OCH3), 2.66 (q, J = 7.6 Hz, 2H, CH2CH3), 1.34 (t, J = 7.6
Hz, 3H, CH2CH3). 13C NMR (CDCl3, 100 MHz): ¤ 160.6,
140.8, 128.4, 127.9, 127.2, 126.9, 125.5, 120.7, 113.8, 113.4,
55.4, 23.7, 13.2. Elemental Anal. Found: C, 66.58; H, 5.88; N,
9.72; Cl, 12.32%. Calcd for C16H17Cl1N2O1: C, 66.55; H, 5.93;
N, 9.70; Cl, 12.28%.
N-(4-Nitrophenyl)benzohydrazonyl
Chloride
(4f):
Known compound;53 1H NMR (DMSO-d6, 400 MHz):
¤
10.72 (s, 1H, NH), 8.18 (apparent d, J = 9.2 Hz, 2H, H-
Ar(NO2)), 8.00-7.92 (m, 2H, H-Ar(NO2)), 7.55-7.46 (m, 5H,
H-Ph).
Cycloaddition Reactions of Iminonitriles to meso-Tetra-
kis(pentafluorophenyl)porphyrin (Table 1). Procedure A:
To a solution of meso-tetrakis(pentafluorophenyl)porphyrin
(6; 98 mg, 0.101 mmol), N-phenylbenzohydrazonyl chloride
(4a; 116 mg, 0.503 mmol) in a dry toluene (2 mL) a solution
of NEt3 (0.4 mL, solution 1.8 mol L¹1) in toluene (2 mL) was
added. Then, the reaction mixture was heated to reflux in a flask
equipped with a reflux condenser protected at the top with a
CaCl2 tube. The new portions of precursor 4a (116 mg, 0.503
mmol; in 2 mL of toluene) were added, followed by addition of
NEt3 (0.4 mL, 1.8 mol L¹1; in 2 mL of toluene) every 9 h. After
45 h the reaction mixture was cooled to room temperature and
Procedure C: A solution of meso-tetrakis(pentafluorophen-
yl)porphyrin (6; 97.5 mg, 0.100 mmol), iminonitrile precursor
4a and 4b (0.40 mmol), and DABCO (45 mg, 0.40 mmol) in
cyclooctane (3 mL) was heated at reflux (under argon) over a
period of ca. 3 h. Then, new portions of iminonitrile precursor
(0.40 mmol) and DABCO (45 mg, 0.40 mmol) were added, and
the reaction was continued for the next 3 h. The products were
isolated as in Procedure B. Yields: chlorin 7a 29 mg, 25% (60%
for converted 6) and porphyrin 8a 12 mg, 10% (24%); chlorin
7b 38 mg, 32% (60%) and porphyrin 8b 6 mg, 5% (9%).
Procedure D:
A solution of meso-tetrakis(pentafluoro-
phenyl)porphyrin (6; 97.5 mg, 0.100 mmol), iminonitrile pre-

1172 Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012)
Synthesis of New PDT Photosensitizers: Pyrazoline-Fused Chlorins
cursor 4a and 4d (0.40 mmol), and NEt3 (120 mg, 1.19 mmol)
in cyclooctane (3 mL) was heated at reflux (under argon) over a
period of ca. 4 h. Then, new portions of iminonitrile precursor
(0.40 mmol) and NEt3 (120 mg, 1.19 mmol) were added, and
the reaction was continued for the next 4 h. The products were
isolated as in Procedure B. Yields: chlorin 7a 34 mg, 29% (40%
for converted 6) and porphyrin 8a 9 mg, 8% (11%); chlorin 7d
9 mg, 7% (16%) and porphyrin 8d 12 mg, 10% (23%).
of CH2CH3), 1.32 (apparent sextet, J µ 14.6, 7.5 Hz, 1H of
CH2CH3), 0.30 (t, J = 7.5 Hz, 3H, CH2CH3), ¹1.80 (s, 1H,
NH), ¹1.82 (s, 1H, NH). NMR-COSY (CDCl3, 400 MHz): ¤
(diagnostic 1H-1H correlations) = ca. 8.68/8.31 (2H¢), ca.
8.68/8.18 (2H¢), 8.53/8.51 (2H¢), 7.40/ca. 7.20 (H-Tol), ca.
7.20/ca. 7.08 (H-Ar(Et)), ca. 7.20/7.03 (H-Ar(Et)), ca. 7.12/
6.71 (2H-chlorin). UV-vis (CHCl3): -max (log ¾) 286 (4.55),
408.5 (5.25, Soret), 507.5 (4.23), 535 (3.78), 603.5 (3.68),
657 nm (4.47). MS (FD), m/z: 1213 (6), 1212 (20), 1211
(64), 1210 (100%) [isotope M+]. HR-MS (FD): M+, found
1210.1868; C60H26N6F20 requires 1210.1900.
1
Chlorin 7a; Mp >300 °C. H NMR (CDCl3, 400 MHz): ¤
8.68 (d, J = 5.0 Hz, 1H, H¢), 8.64 (d, J = 5.0 Hz, 1H, H¢), 8.49
and 8.48 (AB, J µ 5.0 Hz, 2H, 2 © H¢), 8.31 (d, J µ 5.0 Hz,
1H, H¢), 8.24 (d, J µ 5.0 Hz, 1H, H¢), 7.51 (d, J = 8.5 Hz,
1H, CH-chlorin), 7.32-7.22 (m, 3H, H-Ph), 7.15-7.07 (m, 5H,
H-Ph), 6.88 (apparent d, J = 7.3 Hz, 2H, H-Ph), 6.60 (d, 1H,
J = 8.5 Hz, 1H, CH-chlorin), ¹1.54 (s, 2H, 2 © NH). NMR-
COSY (CDCl3, 400 MHz): ¤ (diagnostic 1H-1H correla-
tions) = 8.68/8.31 (2H¢), 8.64/8.24 (2H¢), 7.51/6.60 (2H-
chlorin), ca. 7.10/6.88 (H-Ph). NMR-HSQC (CDCl3, 400/
100 MHz): ¤ (diagnostic 1H-13C correlations) = 7.51/76.6
(CH-chlorin), 6.60/62.6 (CH-chlorin). UV-vis (CHCl3): -max
(log ¾) 409 (5.17, Soret), 508 (4.17), 534 (3.75), 604 (3.65),
657 nm (4.41). MS (ESI): m/z 1172 (9), 1171 (30), 1170 (74),
1169 (100%) [isotope (M + H)+]. HR-MS (ESI): (M + H)+,
found 1169.1533; C57H21N6F20 requires 1169.1508.
1
Chlorin 7e; Mp >300 °C. H NMR (CDCl3, 400 MHz): ¤
8.67 (apparent d, J = 4.9 Hz, 2H, 2 © H¢), 8.52 and 8.50 (AB,
J = 4.7 Hz, 2H, 2 © H¢), 8.30 (d, J = 4.9 Hz, 1H, H¢), 8.18
(d, J = 4.9 Hz, 1H, H¢), 7.43 (apparent d, J = 8.6 Hz, 2H,
H-ArOMe), 7.22-7.16 (m, 1H, H-Ar(Et)), 7.14-7.06 (m, 3H,
2H of H-Ar(Et) and CH-chlorin), 7.02 (d, J = 7.5 Hz, 1H, H-
Ar(Et)), 6.91 (d, J = 8.6 Hz, 2H, H-ArOMe), 6.68 (d, J = 8.3
Hz, 1H, CH-chlorin), 3.93 (s, 3H, OCH3), 1.51-1.36 (m, 2H,
CH2CH3), 0.31 (t, J = 7.5 Hz, 3H, CH2CH3), ¹1.79 (s, 1H,
NH), ¹1.80 (s, 1H, NH). NMR-COSY (CDCl3, 400 MHz): ¤
1
(diagnostic H-1H correlations) = 8.67/8.30 (2H¢), 8.67/8.18
(2H¢), 7.43/6.91 (H-ArOMe), ca. 7.19/ca. 7.09 (H-Ar(Et)),
ca. 7.19/7.02 (H-Ar(Et)), ca. 7.12/ca. 7.09 (H-Ar(Et)), ca.
7.11/6.68 (2H-chlorin), ca. 1.47/0.31 (CH2CH3), ca. 1.39/0.31
(CH2CH3). UV-vis (CHCl3): -max (log ¾) 407.5 (5.45, Soret),
506.5 (4.33), 534 (3.86), 600 (3.78), 653 nm (4.75). MS (FD):
m/z 1229 (7), 1228 (22), 1227 (63), 1226 (100%) [isotope
M+]. HR-MS (FD): M+, found 1226.1906; C60H26N6F20O
requires 1226.1849.
1
Chlorin 7b; Mp >300 °C. H NMR (CDCl3, 400 MHz): ¤
8.66 (d, J = 5.0 Hz, 1H, H¢), 8.63 (d, J = 4.9 Hz, 1H, H¢), 8.48
and 8.47 (AB, J µ 5.0 Hz, 2H, 2 © H¢), 8.30 (d, J = 5.0 Hz,
1H, H¢), 8.23 (d, J = 4.9 Hz, 1H, H¢), 7.46 (d, J = 8.4 Hz,
1H, CH-chlorin), 7.30-7.23 (m, 2H, H-Ph), 7.13-7.06 (m, 3H,
H-Ph), 6.92 (apparent d, J = 8.0 Hz, 2H, H-Tol), 6.78 (apparent
d, J = 8.0 Hz, 2H, H-Tol), 6.57 (d, J = 8.4 Hz, 1H, CH-
chlorin), 2.28 (s, 3H, CH3-Tol), ¹1.56 (s, 2H, 2 © NH). UV-
vis (CHCl3): -max (log ¾) 288 (4.40), 408.5 (5.19, Soret), 508
(4.14), 534.5 (3.68), 603.5 (3.56), 656.5 nm (4.43). MS (FD):
m/z 1185 (5), 1184 (18), 1183 (61), 1182 (100%) [isotope M+].
HR-MS (FD): M+, found 1182.1628; C58H22N6F20 requires
1182.1587.
Porphyrin 8a; Mp >300 °C. 1H NMR (CDCl3, 400 MHz):
¤ 9.02 and 9.00 (AB, J = 4.9 Hz, 2H, 2 © H¢), 8.96 (s, 1H,
H¢), 8.91-8.85 (m, 3H, 3 © H¢), 8.79 (d, J = 4.9 Hz, 1H, H¢),
7.55 (s, 1H, NH), 7.43 (apparent d, J = 7.0 Hz, 2H, H-Ph),
7.29-7.14 (m, 5H, H-Ph), 6.92 (apparent d, J = 8.0 Hz, 2H,
H-Ph), 6.85 (apparent t, J = 7.3 Hz, 1H, H-Ph), ¹2.76 (s, 2H,
2 © NH). UV-vis (CHCl3): -max (log ¾) 364.5 (4.67), 416
(5.47, Soret), 509 (4.26), 589 nm (3.77). MS (ESI): m/z 1173
(4), 1172 (11), 1171 (30), 1170 (71), 1169 (100%) [isotope
(M + H)+]. The molecular formula was confirmed by compar-
ing the theoretical and experimental isotope patterns for the
(M + H)+ ion (C57H21N6F20); it was found to be identical
within the experimental error limits.
Porphyrin 8b; Mp >300 °C. 1H NMR (CDCl3, 400 MHz):
¤ 9.02 and 9.00 (AB, J = 4.9 Hz, 2H, 2 © H¢), 8.96 (s, 1H, H¢),
8.91-8.85 (m, 3H, 3 © H¢), 8.79 (d, J = 4.9 Hz, 1H, H¢), 7.55
(s, 1H, NH), 7.49-7.39 (m, 2H, H-Tol), 7.18 (apparent t, J = 7.9
Hz, 2H, H-Ph), 7.06 (d, J = 8.0 Hz, 2H, H-Tol), 6.89 (apparent
d, J = 8.0 Hz, 2H, H-Ph), 6.83 (apparent t, J = 7.3 Hz, 1H,
H-Ph), 2.34 (s, 3H, CH3-Tol), ¹2.76 (s, 2H, 2 © NH); signal
of ¤ = 7.55 quickly disappeared after addition of D2O. NMR-
COSY (CDCl3, 400 MHz): ¤ (diagnostic 1H-1H correlations) =
ca. 7.43/7.06 (H-Tol), 7.18/6.89 (H-Ph), 7.18/6.83 (H-Ph).
NMR-HSQC (CDCl3, 400/100 MHz): ¤ (diagnostic 1H-13C
correlations) = ca. 9.01/ca. 130.4 (CH¢), 8.96/135.8 (CH¢),
ca. 8.88/ca. 130.0 (CH¢), 8.79/130.4 (CH¢), 7.43/125.2 (CH-
Tol), 7.18/128.9 (CH-Ph), 7.06/128.9 (CH-Tol), 6.89/113.2
(CH-Ph), 6.83/120.3 (CH-Ph), 2.34/21.0 (CH3-Tol). UV-vis
(CHCl3): -max (log ¾) 358.5 (4.82), 416 (5.50, Soret), 509
1
Chlorin 7c; Mp >300 °C. H NMR (CDCl3, 400 MHz): ¤
8.67 (d, J = 5.0 Hz, 1H, H¢), 8.64 (d, J = 5.0 Hz, 1H, H¢), 8.48
and 8.47 (AB, J = 4.7 Hz, 2H, 2 © H¢), 8.30 (d, J = 5.0 Hz,
1H, H¢), 8.25 (d, J = 4.9 Hz, 1H, H¢), 7.50 (d, J = 8.4 Hz, 1H,
CH-chlorin), 7.28 (apparent t, J = 7.8 Hz, 2H, H-Ph), 7.13 (d,
J = 7.9 Hz, 2H, H-Ph), 7.08 (t, J = 7.4 Hz, 1H, H-Ph), 6.80
(apparent d, J = 8.7 Hz, 2H, H-ArOMe), 6.61 (apparent d,
J = 8.7 Hz, 2H, H-ArOMe), 6.52 (d, 1H, J = 8.4 Hz, 1H, CH-
chlorin), 3.72 (s, 3H, OCH3), ¹1.52 (s, 2H, 2 © NH). UV-vis
(CHCl3): -max (log ¾) 287 (4.57), 408.5 (5.28, Soret), 508
(4.25), 534.5 (3.79), 603.5 (3.66), 657.5 nm (4.50). MS (FD):
m/z 1201 (6), 1200 (20), 1199 (64), 1198 (100%) [isotope M+].
HR-MS (FD): M+, found 1198.1494; C58H22N6F20O requires
1198.1536.
1
Chlorin 7d; Mp >300 °C. H NMR (CDCl3, 400 MHz): ¤
8.70-8.65 (m, 2H, 2 © H¢), 8.53 and 8.51 (AB, J = 4.6 Hz,
2H, 2 © H¢), 8.31 (d, J = 4.7 Hz, 1H, H¢), 8.18 (d, J = 4.8 Hz,
1H, H¢), 7.40 (apparent d, J = 8.0 Hz, 2H, H-Tol), 7.23-7.15
(m, 3H, 2H of H-Tol and 1H of H-Ar(Et)), 7.14-7.05 (m, 3H,
2H of H-Ar(Et) and CH-chlorin), 7.03 (apparent d, J = 7.5 Hz,
1H, H-Ar(Et)), 6.71 (d, 1H, J = 8.4 Hz, CH-chlorin), 2.48
(s, 3H, CH3-Tol), 1.49 (apparent sextet, J µ 14.6, 7.5 Hz, 1H

P. Wyrębek et al.
Bull. Chem. Soc. Jpn. Vol. 85, No. 10 (2012) 1173
(4.32), 589 (3.87), 646.5 nm (3.25). MS (FD): m/z 1185 (5),
1184 (20), 1183 (63), 1182 (100%) [isotope M+]. HR-MS (FD):
M+, found 1182.1553; C58H22N6F20 requires 1182.1587.
References
W. Lei, F. Yaqing, Z. Bing, X. Jinqiang, L. Yukun, Prog.
Chem. 2008, 20, 713.
1
1
Porphyrin 8c; Mp >300 °C. H NMR (CDCl3, 400 MHz),
2
A. C. Tomé, M. G. P. M. S. Neves, J. A. S. Cavaleiro,
¤ 9.03 and 9.01 (AB, J = 4.7 Hz, 2H, 2 © H¢), 8.96 (s, 1H,
H¢), 8.91-8.85 (m, 3H, 3 © H¢), 8.80 (d, J = 5.0 Hz, 1H, H¢),
7.49 (s, 1H, NH), 7.49-7.44 (m, 2H, H-ArOMe), 7.20-7.14 (m,
2H, H-Ph), 6.88 (d, J = 7.7 Hz, 2H, H-ArOMe), 6.85-6.76 (m,
3H, H-Ph), 3.79 (s, 3H, OCH3), ¹2.76 (s, 2H, 2 © NH). UV-
vis (CHCl3): -max (log ¾) 300.5 (4.47), 367 (4.72), 416 (5.51,
Soret), 509 (4.32), 589 (3.84), 655 nm (3.34). MS (FD): m/z
1201 (4), 1200 (17), 1199 (58), 1198 (100%) [isotope M+].
HR-MS (FD): M+, found 1198.1489; C58H22N6F20O requires
1198.1536.
J. Porphyrins Phthalocyanines 2009, 13, 408.
3
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4
M. Gałeꢀzowski, D. T. Gryko, J. Org. Chem. 2006, 71,
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Santos, A. C. Tomé, M. G. P. M. S. Neves, J. A. S. Cavaleiro,
Tetrahedron 2008, 64, 7937; and references cited therein.
7
M. Obata, S. Hirohara, R. Tanaka, I. Kinoshita, K. Ohkubo,
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A. P. J. Maestrin, A. O. Ribeiro, A. C. Tedesco, C. R. Neri,
Porphyrin 8d; Mp >300 °C. 1H NMR (CDCl3, 400 MHz):
¤ 9.04 and 9.03 (AB, 2H, J = 5.1 Hz, 2 © H¢), 9.01 (s, 1H,
H¢), 8.95-8.86 (m, 3H, 3 © H¢), 8.81 (d, J = 4.9 Hz, 1H, H¢),
7.89 (s, 1H, NH), 7.78 (apparent d, J = 8.1 Hz, 1H, H-Ar(Et)),
7.41-7.33 (m, 2H, H-Tol), 7.32 (apparent td, J = 7.7, 1.2 Hz,
1H, H-Ar(Et)), 7.03 (apparent d, J = 8.2 Hz, 2H, H-Tol), 6.92-
6.87 (m, 1H, H-Ar(Et)), 6.83 (apparent td, J = 7.3, 0.9 Hz, 1H,
H-Ar(Et)), 2.34 (s, 3H, CH3-Tol), 1.71 (q, J = 7.5 Hz, 2H,
CH2CH3), 0.42 (t, J = 7.5 Hz, 3H, CH2CH3), ¹2.74 (s, 2H,
8
F. S. Vinhado, O. A. Serra, P. R. Martins, Y. Iamamoto, A. M. G.
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P. Saravanan, A. R. Suresh Babu, R. Raghunathan, Synth.
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10 A. M. G. Silva, A. C. Tomé, M. G. P. M. S. Neves, J. A. S.
Cavaleiro, D. Perrone, A. Dondoni, Synlett 2005, 857.
11 H. Hata, Y. Kamimura, H. Shinokubo, A. Osuka, Org. Lett.
2006, 8, 1169.
12 J.-Y. Shin, H. Furuta, K. Yoza, S. Igarashi, A. Osuka, J. Am.
Chem. Soc. 2001, 123, 7190.
13 E. Hao, E. Friso, G. Miotto, G. Jori, M. Soncin, C. Fabris,
M. Sibrian-Vazquez, M. G. H. Vicente, Org. Biomol. Chem. 2008,
6, 3732.
14 A. M. G. Silva, P. S. S. Lacerda, A. C. Tomé, M. G. P. M. S.
Neves, A. M. S. Silva, J. A. S. Cavaleiro, E. A. Makarova, E. A.
Lukyanets, J. Org. Chem. 2006, 71, 8352.
15 A. M. G. Silva, A. C. Tomé, M. G. P. M. S. Neves, J. A. S.
Cavaleiro, Synlett 2002, 1155.
16 A. Desjardins, J. Flemming, E. D. Sternberg, D. Dolphin,
Chem. Commun. 2002, 2622.
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ARKIVOC 2003, Part xiv, 107.
1
2 © NH). NMR-COSY (CDCl3, 400 MHz): ¤ (diagnostic H-
1H correlations) = 7.78/7.32 (H-Ar(Et)), ca. 7.38/7.03 (H-
Tol), 7.32/6.83 (H-Ar(Et)), ca. 6.90/6.83 (H-Ar(Et)). UV-vis
(CHCl3): -max (log ¾) 367 (4.67), 415.5 (5.49, Soret), 508.5
(4.28), 588.5 (3.83), 642.5 nm (3.11). MS (FD): m/z 1213 (4),
1212 (20), 1211 (65), 1210 (100%) [isotope M+]. HR-MS
(FD): M+, found 1210.1858; C60H26N6F20 requires 1210.1900.
Porphyrin 8e; Mp >300 °C. 1H NMR (CDCl3, 400 MHz):
¤ 9.04 and 9.03 (AB, J = 5.2 Hz, 2H, 2 © H¢), 9.01 (s, 1H,
H¢), 8.92-8.86 (m, 3H, 3 © H¢), 8.82 (d, J = 4.9 Hz, 1H, H¢),
7.83 (s, 1H, NH), 7.75 (d, J = 8.2 Hz, 1H, H-Ar(Et)), 7.50-7.35
(m, 2H, H-ArOMe), 7.34-7.28 (m, 1H, H-Ar(Et)), 6.91-6.86
(m, 1H, H-Ar(Et)), 6.82 (apparent td, J = 7.0, 0.5 Hz, 1H, H-
Ar(Et)), 6.76 (apparent d, J = 8.7 Hz, 2H, H-ArOMe), 3.78
(s, 3H, OCH3), 1.70 (q, J = 7.5 Hz, 2H, CH2CH3), 0.42 (t, J =
7.5 Hz, 3H, CH2CH3), ¹2.75 (s, 2H, 2 © NH). NMR-COSY
1
(CDCl3, 400 MHz): ¤ (diagnostic H-1H correlations) = 7.75/
ca. 7.30 (H-Ar(Et)), ca. 7.40/6.76 (H-ArOMe), ca. 7.30/6.82
(H-Ar(Et)), ca. 6.90/6.82 (H-Ar(Et)). UV-vis (CHCl3): -max
(log ¾) 367 (4.82), 416 (5.64, Soret), 509 (4.40), 588.5 (3.89),
644.5 nm (2.99). MS (FD): m/z 1229 (6), 1228 (22), 1227
(64), 1226 (100%) [isotope M+]. HR-MS (FD): M+, found
1226.1880; C60H26N6F20O requires 1226.1849.
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1
1
on the basis of MS and H NMR spectra. H NMR (CDCl3,
400 MHz): ¤ (diagnostic chemical shift) = ¹3.57 (s, 2H, 2 ©
NH). MS (ESI): m/z 1365 (41), 1364 (82), 1363 (100%)
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and No. N N204 135438 (2010-2011).

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