ROM polymerization-capture-release strategy for the chromatography-free synthesis of novel unsymmetrical porphyrazines

Article abstract of DOI:10.1021/jo047792q

(Chemical Equation Presented) Crossover-Linstead macrocyclization reactions of two norbornenyl-tagged diaminomaleonitriles with dipropylmaleonitrile gave access to crude mixtures of porphyrazines containing diamino-hexapropyl- porphyrazine magnesium compl

Full text of DOI:10.1021/jo047792q

ROM Polymerization-Capture-Release Strategy for the
Chromatography-Free Synthesis of Novel Unsymmetrical
Porphyrazines
Matthew J. Fuchter,† Benjamin J. Vesper,‡ Karen A. Murphy,† Hazel A. Collins,†
David Phillips,† Anthony G. M. Barrett,*,† and Brian M. Hoffman*,‡
Department of Chemistry, Imperial College London, London SW7 2AZ, U.K., and Department of
Chemistry, Northwestern University, Evanston, Illinois 60208
agmb@imperial.ac.uk; bmh@northwestern.edu
Received December 17, 2004
Crossover-Linstead macrocyclization reactions of two norbornenyl-tagged diaminomaleonitriles with
dipropylmaleonitrile gave access to crude mixtures of porphyrazines containing diamino-hexapropyl-
porphyrazine magnesium complexes. The mixtures were subjected to ring-opening metathesis
polymerization to yield the insoluble diaminoporphyrazine-functionalized polymers. Acid-mediated
cleavage from the polymer backbone followed by acylation of the resultant sensitive macrocyclic
diamines gave monoacetyl-, monotrifluoroacetyl-, and ditrifluoroacetyl-substituted porphyrazinedi-
amines. Conversion of these amido-porphyrazines to the corresponding zinc macrocycles and studies
of their electronic absorption and emission spectra, electrochemistry, and photophysics are described.
Introduction
the Linstead macrocyclization5 of acyclic maleonitriles is
still the only widely used method for porphyrazine
synthesis. Although it is hard to picture a faster or more
versatile route, the procedure is frequently plagued with
poor yields and difficulties with purification. In addition,
the selective synthesis of specific constitutional isomers
from the crossover macrocyclization of two different
maleonitriles (respectively functionalized by A and B) is
limited. For phthalocyanines, methods to achieve direct
synthesis of specific isomers include the linking of two
phthalonitrile units prior to macrocyclization,6,7 ring
expansion of a subphthalocyanine,8,9 solid-phase synthe-
sis,10,11 and the preparation of “half-phthalocyanine”
intermediates.12 For porphyrazines, the employment of
Porphyrazines are structural variants of porphyrins,
with meso nitrogen atoms replacing the meso carbon
atoms. Although the related porphyrins and phthalocya-
nines have received considerable interest and detailed
studies into their synthesis, properties, and applications
have been reported,1,2 porphyrazines have received sig-
nificantly less attention. Peripheral heteroatom func-
tionalization of the macrocycle results in significant
modulation of their physical and electronic properties.3
Barrett, Hoffman, and co-workers have published exten-
sively on the synthesis of porphyrazines bearing thiols,
amines, or alcohols as ring substituents and with the
conversion of these polydentate ligands to a variety of
coordination complexes.3,4 Since its development in 1952,
(4) Michel, S. L.; Baum, S.; Barrett, A. G. M.; Hoffman, B. M. In
Progress in Inorganic Chemistry; Karlin, K. D., Ed.; Wiley & Sons: New
York, 2001; Vol. 50, p 473.
(5) Linstead, R. P.; Whalley, M. J. Chem. Soc. 1952, 4839.
(6) Kobayashi, N.; Kobayashi, Y.; Osa, T. J. Am. Chem. Soc. 1993,
115, 10994.
† Imperial College London.
‡ Northwestern University.
(1) The Porphyrins; Dolphin, D., Ed.; Academic Press: New York,
1978-1979; Vol. 1-7.
(2) Phthalocyanines: Properties and Applications; Leznoff, C. C.,
Lever, A. B. P., Eds.; VCH Publishers: Weinheim, Germany, 1989-
1996; Vol. 1-4.
(7) Drew, D. M.; Leznoff, C. C. Synlett 1994, 623.
(8) Kobayashi, N.; Kondo, R.; Nakajima, S.-I.; Osa, T. J. Am. Chem.
Soc. 1990, 112, 9640.
(3) Stuzhin, P. A.; Ercolani, C. In The Porphyrin Handbook; Kadish,
K. M., Smith, K. M., Guilard, R., Eds.; Academic Press: New York,
2003; Vol. 15, p 263.
(9) Kobayashi, N.; Ishizaki, T.; Ishii, K.; Konami, H. J. Am. Chem.
Soc. 1999, 121, 9096.
(10) Leznoff, C. C.; Hall, T. W. Tetrahedron Lett. 1982, 23, 3023.
10.1021/jo047792q CCC: $30.25 © 2005 American Chemical Society
Published on Web 03/02/2005
J. Org. Chem. 2005, 70, 2793-2802
2793

Fuchter et al.
SCHEME 1
dinitriles bearing bulky groups (trans directors) to give
trans-A2B2 porphyrazines selectively has been demon-
strated.13 Statistical cyclization of two maleonitrile com-
ponents, resulting in a mixture of constitutional isomers,
is currently the only viable method for the synthesis of
unsymmetrical porphyrazines (A3B). Drawing on experi-
ence in ring-opening metathesis (ROM) polymerization14
and impurity annihilation,15 we sought to improve the
synthetic strategy for elaborating polyfunctional por-
phyrazines. Hanson and co-workers have recently dem-
onstrated the application of chemically tagged reagents
for the synthesis of o-alkylhydroxylamines, amines, and
alkyl hydrazines.16,17 The principle of employing a nor-
bornenyl-tagged reagent, with solution-phase Linstead
macrocyclization and subsequent selective capture of the
desired porphyrazine by ROM polymerization, is appeal-
ing. Cleavage of the macrocycle from the ROM polymer
should deliver the pure porphyrazine without the need
for extensive chromatography. Ruthenium alkene me-
tathesis catalysts, developed by Grubbs,18,19 have been
previously applied to the synthesis of polymeric por-
phyrazine structures20 and therefore should be ideal for
this application.
nesium butoxide used in the cyclization, which destroyed
the active catalyst. However, all attempts to neutralize
the residual base prior to polymerization using stoichio-
metric quantities of acetic acid, acid-washed Celite,
carboxylic acid-functionalized Amberlyst resin, or silica
gel failed to facilitate polymerization. Finally, rapid
filtration of the crude mixture through silica followed by
evaporation of the filtrate and reaction of the residue with
catalyst 10 resulted in the formation of ROM polymer 9
as an insoluble blue solid.
Results and Discussion
Norbornenyl-tagged dinitrile 5 was prepared in four
steps from diaminomaleonitrile and known tosylate 1,21
which was converted into aldehyde 2 by reaction with
cesium carbonate and 4-hydroxybenzaldehyde. Following
the procedure of Sheppard and co-workers,22 condensa-
tion of aldehyde 2 and diaminomaleonitrile gave imine
3, which was subsequently reduced with sodium boro-
hydride. Resultant maleonitrile 4, which was obtained
in 70% yield over two steps, was used directly without
further purification. Methylation using dimethyl sulfate
and sodium hydride gave tagged aminomaleonitrile 5 in
93% yield (Scheme 1).
Macrocyclization of aminomaleonitrile 5 and dipropyl-
maleonitrile 6 (9.9 equiv)23 gave a crude mixture of dyes
containing porphyrazines 7 and 8, as identified by FAB
mass spectrometry (Scheme 2). Unfortunately, treatment
of this mixture with Grubbs’ second-generation catalyst
1018,19 and cross-linker 11 under standard ROM polym-
erization conditions14 gave no polymeric products. This
was initially attributed to the presence of excess mag-
Treatment of ROM polymer 9 with TFA in dichlo-
romethane resulted in the simultaneous cleavage of the
linker and demetalation of the supported porphyrazine
to give the expected macrocycle 12 (Scheme 2). Under
optimum conditions, addition of a 10% solution of TFA
in dichloromethane to ROM polymer 9 followed by
stirring at ambient temperature for 1 h gave porphyra-
zine 12 (17% overall from 5) after filtration through silica.
This yield is comparable to structurally similar free-base
porphyrazine 13, which was obtained after chromatog-
raphy in 19% yield.24 The analogous yields imply that
the lowest yielding step is the macrocyclization reaction,
with both polymerization and cleavage presumably oc-
curring efficiently. Porphyrazine 12 proved to be un-
stable, even when stored under argon at -18 °C. This
was presumably due to the increased electron donation
of the free amino functionality into the ring system,
leading to an electron-rich macrocycle prone to oxidative
degradation. It was therefore not straightforward to
determine the purity of porphyrazine 12, and only limited
characterization was achieved. However, porphyrazine
12 was successfully converted into other more robust
derivatives. Attempted methylation using methyl iodide
at reflux or dimethyl sulfate at room temperature under
basic conditions, central metalation of porphyrazine 12
using zinc acetate, or peripheral metalation using pal-
(11) Hirth, A.; Sobbi, A. K.; Wo¨hrle, D. J. Porphyrins Phthalocya-
nines 1997, 1, 275.
(12) Nolan, K. J. M.; Hu, M.; Leznoff, C. C. Synlett 1997, 593.
(13) Forsyth, T. P.; Williams, D. B. G.; Montalban, A. G.; Stern, C.
L.; Barrett, A. G. M.; Hoffman, B. M. J. Org. Chem. 1998, 63, 331.
(14) Barrett, A. G. M.; Hopkins, B. T.; Ko¨bberling, J. Chem. Rev.
2002, 102, 3301.
(15) Barrett, A. G. M.; Smith, M. L.; Zecri, F. Chem. Commun. 1998,
2317.
(16) Harned, A. M.; Hanson, P. R. Org. Lett. 2002, 4, 1007.
(17) Mukherjee, S.; Poon, K. W. C.; Flynn, D. L.; Hanson, P. R.
Tetrahedron Lett. 2003, 44, 7187.
(18) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18.
(19) Bielawski, C. W.; Grubbs, R. H. Angew. Chem., Int. Ed. 2000,
39, 2903.
(20) Montalban, A. G.; Steinke, J. H. G.; Anderson, M. E.; Barrett,
A. G. M.; Hoffman, B. M. Tetrahedron Lett. 1999, 40, 8151.
(21) Billet, E. H.; Fleming, I.; Hanson, S. W. J. Chem. Soc., Perkin
Trans. 1973, 1, 1661.
24
ladium(II) chloride or (PhCN)2PtCl2 resulted only in
(22) Begland, R. W.; Hartter, D. R.; Jones, F. N.; Sam, D. J.;
Sheppard, W. A.; Webster, O. W.; Weigert, F. J. J. Org. Chem. 1974,
39, 2341.
(24) Lange, S. J.; Nie, H.; Stern, C. L.; Barrett, A. G. M.; Hoffman,
B. M. Inorg. Chem. 1998, 37, 6435.
(23) Fitzgerald, J.; Taylor, W.; Owen, H. Synthesis 1991, 686.
2794 J. Org. Chem., Vol. 70, No. 7, 2005

Synthesis of Novel Unsymmetrical Porphyrazines
SCHEME 2
SCHEME 3
decomposition. The reaction of porphyrazine 12 with
benzoyl or acetyl chloride and zinc acetate in pyridine at
reflux, a solvent known to hinder oxidative degradation,25
was examined in an attempt to both metalate the
macrocycle and acylate the free amino group. Both
reactions gave amide 15 as the sole product. Presumably,
with benzoyl chloride, this arose from the formation of
benzoic acetic anhydride. When optimized, reflux of
macrocycle 12 and acetic anhydride in degassed pyridine
gave amide 15 (95%). Similarly, acylation of porphyrazine
12 with trifluoroacetic anhydride in pyridine at 0 °C gave
trifluoroacetamide 16 (65%) (Scheme 3).
In a modified procedure, porphyrazine 12 was allowed
to react with either acetic anhydride or trifluoroacetic
anhydride, with ScavengePore phenethyl piperidine added
to remove excess anhydride. The solvent was evaporated
under reduced pressure, and the product was filtered
through silica to remove decomposition products. In the
case of trifluoroacetylated product 15, an additional
aqueous workup was employed to remove residual salts,
which could not be precipitated out of solution, prior to
filtration. This gave porphyrazines 15 and 16 in >99 and
93% purity, respectively, as judged by HPLC. Porphyra-
zines 15 and 16 were readily converted to their zinc
derivatives (17 and 18) using standard methods (Scheme
3). Interestingly, the NMR spectra of zinc porphyrazines
17 and 18 had to be recorded in pyridine-d5 to avoid
severe broadening of the peaks. As noted for the seco-
pophryazines,25 this can be attributed to the formation
of dimer pairs via coordination of the amido oxygen atoms
(25) Montalban, A. G.; Lange, S. J.; Beall, L. S.; Mani, N. S.;
Williams, D. J.; White, A. J. P.; Barrett, A. G. M.; Hoffman, B. M. J.
Org. Chem. 1997, 62, 9284.
to the apical site of the square-pyramidal zinc(II) center
of the adjacent macrocycle.
J. Org. Chem, Vol. 70, No. 7, 2005 2795

Fuchter et al.
FIGURE 1. UV-vis spectra for porphyrazines 13-18 in CH2-
Cl2.
The electronic absorption spectra of porphyrazines 13-
18 are shown in Figure 1. Free-base porphyrazines 15
and 16 exhibit complex red-shifted Q bands in compari-
son to previously reported free-base A3B porphyrazine
13.25 The spectra contain qualitatively similar absor-
bances at 342, 549, 591, and 668 nm and 344, 540, 595,
and 670 nm, respectively. The broadened, complex Q
band is a result of the reduced symmetry of the macro-
cycles in accordance with Gouterman’s four-orbital model26
as well as the electronic decoupling of one of the periph-
eral nitrogen lone pairs from the macrocyclic core by the
electron-withdrawing acetyl or trifluoroacetyl groups. In
addition, underlying n-π* transitions of the remaining
lone pairs into a π* ring orbital complicate the spectra.4
The broadened transition for metalated A3B porphyrazine
1425 conceals the split of the Q band that is expected for
the lower (C2v) symmetry.26 Once again, macrocycles 17
and 18 display spectra with qualitatively similar absor-
bances at 342, 508, and 626 nm and 342, 490, and 630
nm, respectively, which are red-shifted compared to those
of structurally similar porphyrazine 14. As with the free-
base porphyrazines, substitution of the electronically
deactivating acetyl and trifluoroacetyl groups results in
desymmetrization of the π chromophore and subsequent
disruption of the Q band transitions. Representative
absorption and emission spectra of zinc porphyrazines
17 and 18 are shown in Figure 2.
The significant donation of electron density from the
peripheral amino groups into the macrocyclic ring system
has been previously demonstrated by cyclic voltamme-
try.4 Consequently, these porphyrazines are more easily
oxidized than the analogous phthalocyanines and por-
phyrins. However, substitution of an electronically with-
drawing acetyl or trifluoroacetyl group should result in
an increase in the oxidation potential of the resulting
porphyrazines, which leads to a macrocycle that is more
difficult to oxidize. Indeed, the first oxidation potentials
of 15 and 17 are 0.135 and 0.138 V, respectively, indi-
cating that the macrocycles are at least 265 mV more
FIGURE 2. Absorption and emission spectra of (a) 17 and
(b) 18 in toluene, λex ) 511 and 485, respectively.
difficult to oxidize than 13 (Figure 3, Table 1). Addition-
ally, trifluoroacetyl-functionalized porphyrazines 16 and
18 exhibit first oxidation potentials at 0.287 and 0.306
V, respectively, demonstrating that the macrocycles are
at least 417 mV more difficult to oxidize than 13 (Table
1). Free-base porphyrazines 15 and 16 also exhibit two
reversible ring-based reductions at -1.57, -1.99 and
-1.476, -1.89 V, respectively (Table 1). Although meta-
lation with the redox-inactive zinc appears not to influ-
ence the macrocycle-based ring properties greatly, the
second reduction potentials for porphyrazines 17 and 18
are shifted to potentials more negative than the window
of the experiment following metalation.
The increased oxidation potential of porphyrazine 17
is reflected in the chemical oxidation to corresponding
seco-porphyrazine 19 (Scheme 3). Treatment of porphyra-
zine 17 with potassium permanganate in dichloromethane
for 3 h resulted in only trace amounts of seco derivative
19. Previously, macrocycle 14 was converted to the
corresponding seco-porphyrazine in almost quantitative
yield using analogous conditions.25 Alternatively, aerobic
oxidation could be affected by stirring a dichloromethane
solution containing 17 for a total of 8 days, periodically
isolating small quantities of seco derivative 19.
The electronic absorption spectrum of seco derivative
19 exhibits the characteristic split Soret and Q bands
that are observed for the seco-porphyrazines, with ab-
sorbances at 341, 357, 572, and 651 nm, whereas the
emission spectrum (λex ) 566 nm) displays a maxima at
(26) Gouterman, M. In The Porphyrins; Dolphin, D., Ed.; Academic
Press: New York, 1978; Vol. 3, p 1.
2796 J. Org. Chem., Vol. 70, No. 7, 2005

Synthesis of Novel Unsymmetrical Porphyrazines
SCHEME 4
FIGURE 3. Cyclic voltammograms of porphyrazines 15 and
17.
TABLE 1. Electrochemical Study of Porphyrazines
15-18
comparison of half-wave potentials
(V vs Fc+/Fc)a, E1/2 (∆Ep, mV)
pz2+/pz+
pz+/pz
pz/pz1-
pz1-/pz2-
134
15
16
17
18
+0.43(66)
+0.584(88)
+0.781(82)
+0.572(72)
+0.660(88)
-0.13(70)
-1.39(76)
-1.84(94)
-1.99(120)
-1.89(116)
+0.135(86)
+0.287(86)
+0.138(84)
+0.306(264)
-1.570(116)
-1.476(128)
-1.565(82)
-1.532(164)
a Measured in dichloromethane with 0.1 M Bu4NPF6 as the
electrolyte and a Pt disk working electrode at a scan rate of 110
mV s-1
.
713 nm. The photophysical profiles of zinc derivatives 17
and 18 as well as seco-porphyrazine 19 were determined.
Previously, it has been suggested that because of the
minimal fluorescence or intersystem crossing observed
for porphyrazine 14 the dominant deactivation pathway
for the first excited singlet state is internal conversion
to the ground state followed by vibrational relaxation.27
The vibrational relaxation is aided by the strong coupling
of the nonbonding electron pairs of the peripheral nitro-
gen atoms to the macrocyclic core. Conversion of 14 to
the corresponding seco-porphyrazine, however, results in
decoupling of the lone-pair electrons from the ring, and
the subsequent macrocycle displays high quantum yields
for both intersystem crossing (ΦΤ ) 0.64) and quenching
(Φ∆ ) 0.54).27 The high quantum yield of triplet-state
formation is also attributed to the amido carbonyl groups,
which are known to promote intersystem crossing.28
Decoupling of the lone-pair electrons by the acetyl or
trifluoroacetyl groups in 17 and 18 should also hinder
vibrational relaxation, therefore promoting intersystem
crossing aided by the carbonyl groups. Indeed, macro-
cycles 17 and 18 display singlet-oxygen quantum yields
of 0.30 and 0.69, respectively. This reinforces the as-
sumption that decoupling of the nitrogen lone pairs from
the ring system facilitates intersystem crossing. Alter-
natively, the conformation of the amido functionality
could provide a steric barrier, preventing the lone-pair
electrons on the neighboring amino group from fully
conjugating with the ring system. Also, seco-porphyrazine
19 exhibits a singlet-oxygen quantum yield of 0.87, which
is the highest value recorded for the seco-porphyrazines
so far.29 Presumably, the newly formed imido functional-
ity efficiently aids intersystem crossing. In addition, the
fluorescence quantum yields for porphyrazines 17, 18,
and 19 are 0.01, 0.07, and 0.02, respectively, with
corresponding lifetimes of 0.91, 2.40, and 0.70 ns. There-
fore, for these macrocycles, relaxation via fluorescence
is only a minor deactivation pathway.
In an attempt to extend this methodology, doubly
tagged maleonitrile 22 was prepared in three steps from
aldehyde 2 and dinitrile 4. Condensation of aldehyde 2
and amine 4 in methanol with TFA catalysis gave imine
20, which was subsequently reduced with sodium boro-
hydride to give doubly tagged maleonitrile 21 in 89%
yield in two steps. This was used without further
purification. Methylation of dinitrile 21, as before, gave
doubly tagged dinitrile 22 in good yield (Scheme 4).
Crossover macrocyclization of aminomaleonitrile 22
and dipropylmaleonitrile 6 and ROM polymerization
using catalyst 10 and cross-linker 11 gave heavily cross-
linked ROM polymer 23 as a blue solid (Scheme 5).
Treatment of polymer 23 with 10% TFA in dichlo-
romethane failed to release any significant amount of
porphyrazinic products, whereas only decomposition was
observed at higher concentrations of TFA. In contrast,
polymer 23 was allowed to stand in dichloromethane
containing 1 M triflic acid and 2 M TFA for 1 h at room
(27) Montalban, A. G.; Meunier, H. G.; Ostler, R. B.; Barrett, A. G.
M.; Hoffman, B. M.; Rumbles, G. J. Phys. Chem. 1999, 103, 4352.
(28) Gilbert, G.; Baggott, J. Essentials of Molecular Photochemistry;
Blackwell: Cambridge, MA, 1991; p 126.
(29) Montalban, A. G.; Baum, S.; Hoffman, B. M.; Barrett, A. G. M.
J. Chem. Soc., Dalton Trans. 2003, 2093.
J. Org. Chem, Vol. 70, No. 7, 2005 2797

Fuchter et al.
SCHEME 5
temperature (Scheme 5) to release the unstable and
easily oxidized porphyrazine 24, which was used im-
mediately for further transformations. Interestingly, the
presence of triflic acid resulted in the standard purple
porphyrazine color being replaced by brown for the
duration of the cleavage, presumably due to protonation
of the meso nitrogen atoms and disrupted aromaticity.
Unfortunately, functionalization of porphyrazine 24
was also problematic, and attempts to prepare acetamide
derivatives were unsuccessful. Crude porphyrazine 24
was allowed to react with trifluoroacetic anhydride in
degassed pyridine at 0 °C to give a mixture of mono- and
diamido porphyrazines 25 and 26, which were separated
by chromatography. Monoamide 25 was reacylated to
yield additional diamido porphyrazine 26, which could
be isolated by filtration though silica in 5% yield in five
steps from maleonitrile 22 and with >99% purity as
judged by HPLC (Scheme 5). Porphyrazine 26 also
displayed broadening of the NMR spectra in deuterated
chloroform but displayed a clear NMR spectrum in
pyridine-d5. Reaction of porphyrazine 26 with zinc acetate
in DMF at 80 °C gave zinc derivative 27, which resulted
from concomitant metalation and partial deacylation.
The electronic absorption spectra for free-base 26 and
novel zinc derivative 27 are shown in Figure 4. The
spectra resemble the previously encountered spectra for
A3B porphyrazines 13 and 14 (Figure 1). The broadening
effect of the nitrogen nonbonding electrons (vide supra)
is no longer apparent, and both 26 and 27 display
sharpened, well-defined spectra. This has been observed
previously on decoupling of the nitrogen lone pairs from
the ring system following oxidation29 or peripheral meta-
FIGURE 4. UV-vis spectra for porphyrazines 26 and 27 in
CH2Cl2.
lation.24,30 Immediately, this suggests that the electroni-
cally deactivating trifluororacetyl groups prevent cou-
pling of the nitrogen lone-pair electrons to the macrocyclic
ring. Porphyrazine 26 exhibits a red-shifted, split Q band
with Qx and Qy absorbances at 585 and 616 nm. The
splitting can be assigned to the reduced symmetry of the
free-base macrocycle. Zinc derivative 27 displays a
broadened Q band centered around 617 nm with ad-
(30) Goldberg, D. P.; Michel, S. L.; White, A. J. P.; Williams, D. J.;
Barrett, A. G. M.; Hoffman, B. M. Inorg. Chem. 1998, 37, 2100.
2798 J. Org. Chem., Vol. 70, No. 7, 2005

Synthesis of Novel Unsymmetrical Porphyrazines
TABLE 2. Electrochemical Study of Porphyrazines 26
and 27
electrons with the ring system and the efficiency of
sensitization to produce singlet oxygen has been con-
firmed. Furthermore, novel trifluoroacetylated porphyra-
zine 27 exhibits an excellent singlet-oxygen quantum
yield (Φ∆ ) 0.88) and is the most potent porphyrazine
sensitizer synthesized to date. The synthetic flexibility
of this novel methodology for the synthesis of other
porphyrazine derivatives will be the subject of future
reports.
comparison of half-wave potentials
(V vs Fc+/Fc)a, E1/2 (∆Ep, mV)
pz2+/pz+
pz+/pz
+0.838(122) -1.184(102) -1.591(120)
27 +0.737(148) +0.237(72) -1.526(164)
pz/pz1-
pz1-/pz2-
26
a Measured in dichloromethane with 0.1 M Bu4NPF6 as the
electrolyte and a Pt disk working electrode at a scan rate of 110
mV s-1
.
Experimental Section
ditional shoulders at 572 and 644 nm. The emission
spectrum of porphyrazine 27 (λex ) 346 nm) displays a
maxima at 659 nm.
4-(Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzalde-
hyde (2). 4-Hydroxybenzaldehyde (1.32 g, 10.8 mmol) was
added to tosylate 121 (3.0 g, 10.8 mmol) and Cs2CO3 (5.27 g,
16.2 mmol) in DMF (20 mL) under N2. The mixture was heated
to 100 °C for 16 h, poured into H2O (50 mL), and extracted
with Et2O (3 × 50 mL). The combined organic extracts were
washed with saturated aqueous NH4Cl (3 × 50 mL), dried
(MgSO4), filtered, and rotary evaporated. Chromatography
(SiO2, hexanes/EtOAc, 9:1) gave aldehyde 2 (2.37 g, 96%) as a
colorless oil containing a mixture of isomers. Rf : 0.33 (hex-
anes/EtOAc, 9:1); IR (neat): 1692, 1640, 1510, 1256, 1159, 1015
Substitution of two electronically deactivating trifluo-
roacetyl groups onto the peripheral amino groups should
result in complete decoupling of the nonbonding elec-
trons, leading to an increase in the oxidation potential
of the resulting porphyrazines. Consequently, the first
oxidation potential of porphyrazine 26 is +0.838 V,
indicating that the macrocycle is 968 mV more difficult
to oxidize than free base 13 (Table 2). Impressively, this
compound is more difficult to oxidize than the octapropyl-
and octamethylthioporphyrazines, which display a re-
versible oxidation in the +0.65-0.70 V region.4 Free-base
porphyrazine 26 also exhibits two reversible ring-based
reductions at -1.18 and -1.59 V. (Table 2). Alternatively,
novel zinc derivative 27 displays vastly different redox
potentials than free-base 26. The first oxidation potential
of 27 is +0.237 V; it is 69 mV easier to oxidize than the
related monotrifluoroacetylated porphyrazine 18. In gen-
eral, the redox potentials for 27 mirror those of the
monoacetylated macrocycles (see Table 1).
The photophysical profile of zinc derivative 27 was
determined. As previously stated, decoupling of the lone-
pair electrons by the trifluoroacetyl groups hinders
vibrational relaxation, therefore promoting intersystem
crossing aided by the carbonyl groups (vide supra).
Curiously, macrocycle 27 displays an impressive singlet-
oxygen quantum yield of 0.88. This superb result is
comparable to seco-porphyrazine 19, and porphyrazine
27 therefore shows the highest photosensitizing ability
of any of the porphyrazine macrocycles reported to date.
The reason that novel derivative 27 has an increasing
sensitizing ability relative to monotrifluoroacetylated
porphyrazine 17 is yet to be established, and further
studies are underway. Porphyrazine 27 showed a fluo-
rescence quantum yield of 0.10 with a corresponding
lifetime of 2.70 ns.
cm-1 1H NMR (300 MHz, CDCl3, δ): 0.64 (app-d, J ) 10.0
;
Hz, 1H), 1.35 (m, 1H), 1.50 (m, 1H), 1.95 (m, 1H), 2.59 (br m,
1H), 2.88 (br m, 1H), 3.06 (br m, 1H), 3.65 (t, J ) 9.0 Hz, 1H),
3.80 (m, 1H), 5.97 (br m, 1H), 6.20 (m, 1H), 6.99 (d, J ) 9.0
Hz, 2H), 7.82 (d, J ) 9.0 Hz, 2H), 9.89 (s, 1H); 13C NMR (75
MHz, CDCl3, δ): 29.0, 38.5, 42.3, 43.9, 49.5, 71.9, 114.8, 129.7,
132.0, 132.2, 137.8, 164.3, 190.9; MS (CI) m/z: 229 [M + H]+;
HRMS (CI): [M + H]+ calcd for C15H17O2, 229.1229; found,
229.1224. Anal. Calcd for C15H16O2: C, 78.92; H, 7.06. Found:
C, 79.00; H, 7.00.
2-Amino-3-([4-(bicyclo[2.2.1]hept-5-en-2-ylmethoxy)-
benzylidene]amino)but-2-enedinitrile (3). Diaminomaleo-
nitrile (1.04 g, 9.6 mmol) and aldehyde 2 (2.20 g, 9.6 mmol) in
EtOH (10 mL) were heated to reflux overnight. The yellow
solid, which precipitated out of the solution, was filtered off
and washed with cold EtOH (5 mL). The filtrate was heated
to reflux for another 4 h, and the precipitated solid was filtered,
washed, and combined with the previous crop. This gave imine
3 (2.25 g, 73%) as a yellow solid containing a mixture of
isomers, which was used without further purification: mp
207-209 °C; IR (neat): 3411, 3297, 2245, 2205, 1606, 1249,
826 cm-1; 1H NMR (300 MHz, DMSO-d6, δ): 0.64 (app-d, J )
10.0 Hz, 1H), 1.31 (m, 1H), 1.50 (m, 1H), 1.95 (m, 1H), 2.50
(m, 1H, obscured by DMSO), 2.88 (br m, 1H), 3.06 (br m, 1H),
3.64 (t, J ) 9.0 Hz, 1H), 3.77 (m, 1H), 5.98 (br m, 1H), 6.21
(m, 1H), 6.99 (d, J ) 8.0 Hz, 2H), 7.76 (br s, 2H), 7.99 (d, J )
8.0 Hz, 2H), 8.20 (s, 1H); 13C NMR (125 MHz, DMSO-d6, δ):
28.7, 37.8, 41.7, 43.4, 49.0, 71.4, 103.1, 113.9, 114.6, 114.7,
125.9, 128.3, 131.0, 132.2, 137.5, 154.7, 161.6; MS (CI) m/z:
319 [M + H]+; HRMS (CI): [M + H]+ calcd for C19H19N4O,
319.1559; found, 319.1565.
2-Amino-3-[4-(bicyclo[2.2.1]hept-5-en-2-ylmethoxy)ben-
zylamino]but-2-enedinitrile (4). NaBH4 (0.36 g, 9.5 mmol)
was added in portions to a suspension of imine 3 (1.01 g, 3.17
mmol) in dry THF (15 mL) and MeOH (10 mL) under N2. The
slurry was stirred for 2 h, during which the mixture turned
homogeneous. The solution was poured into ice/H2O (150 mL),
the resultant cream solid was filtered off, and the residual H2O
was removed by azeotrope with PhMe (2 × 30 mL). This gave
amine 4 (0.97 g, 96%) as a brown solid containing a mixture
of isomers, which was used without further purification: mp
163-165 °C; IR (neat): 3329, 2218, 2204, 1618, 1510, 1379,
Conclusions
The development and application of a new ROM
polymerization-release strategy for the selective syn-
thesis of novel A3B amino porphyrazines has been
described. Acetyl or trifluoroacetyl substitution of the
peripheral amino groups resulted in profound differences
in the electronic structure of each macrocycle. All of the
amido-functionalized porphyrazines showed increased
oxidation potentials compared to the corresponding di-
alkylamino-substituted porphyrazines as a result of the
reduced electron donation into the macrocycle by the
nitrogen-centered substituents. Additionally, the rela-
tionship between the coupling of the nitrogen nonbonding
1
1238 cm-1; H NMR (300 MHz, DMSO-d6, δ): 0.59 (app-d, J
) 11.0 Hz, 1H), 1.29 (m, 2H), 1.87 (m, 1H), 2.50 (m, 1H,
obscured by DMSO), 2.86 (br m, 1H), 2.96 (br m, 1H), 3.51 (t,
J ) 9.0 Hz, 1H), 3.67 (m, 1H), 4.14 (d, J ) 5.0 Hz, 2H), 5.62
(br m, 3H), 5.95 (m, 1H), 6.19 (m, 1H), 6.89 (d, J ) 8.0 Hz,
2H), 7.18 (d, J ) 8.0 Hz, 2H); 13C NMR (125 MHz, DMSO-d6,
J. Org. Chem, Vol. 70, No. 7, 2005 2799

Fuchter et al.
δ): 28.7, 37.8, 41.7, 43.4, 48.4, 48.9, 71.0, 107.6, 108.2, 114.4,
115.8, 116.7, 128.6, 130.9, 132.1, 137.3, 157.9; MS (CI) m/z:
338 [M + NH4]+; HRMS (CI): [M + NH4]+ calcd for C19H24N5O,
338.1981; found, 338.1986.
added, and the resulting suspension was heated at reflux for
1 h. After rotary evaporation, Et2O (20 mL) was added to the
residue, the mixture was filtered, and the filtrate was evapo-
rated under reduced pressure. The product in hexanes/EtOAc
(7:3) was filtered through silica to give amide 15 as a purple/
blue solid (7.6 mg, 95%). Rf : 0.23 (hexanes/EtOAc, 6:4);
HPLC: PHPLC ) 100%, tR ) 16.5 min; IR (neat): 3311, 1669,
1603, 1463, 1146 cm-1; UV-vis (CH2Cl2) λmax (log ꢀ) 342 (4.08),
549 (3.50), 591 (3.61), 617 (3.59), 668 (3.56) nm; 1H NMR (500
MHz, CDCl3, δ): -1.60 (br s, 2H), 1.20 (t, J ) 3 Hz, 3H), 1.25
(m, 15H), 2.19 (s, 3H), 2.31 (m, 12H), 3.78 (m, 7H), 3.92 (m,
8H), 4.14 (s, 6H); 13C NMR (125 MHz, CDCl3, δ): 14.5, 14.7,
14.8, 22.9, 25.3, 25.4, 25.5, 27.7, 28.0, 28.1, 28.2, 29.7, 39.2,
43.2, 117.7, 139.8, 141.2, 142.2, 142.6, 144.3, 144.9, 145.0,
145.2, 148.1, 148.5, 153.3, 159.4, 160.5, 162.6, 174.0; MS (FAB)
m/z: 681 [M+•]; HRMS (FAB): [M+•] calcd for C39H56N10O,
680.4639; found, 680.4643.
2-([4-(Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzyl]meth-
ylamino)-3-(dimethylamino)-but-2-enedinitrile (5). Dini-
trile 4 (0.86 g, 2.7 mmol) in dry THF (10 mL) was added to
NaH (0.54 g, 13.5 mmol, 60% suspension in mineral oil) in
dry THF (20 mL) at -30 °C under N2. The mixture was allowed
to warm to -10 °C, and dimethyl sulfate (1.28 mL, 13.5 mmol)
was added over 30 min, after which the mixture was allowed
to warm to 20 °C and stirred for 18 h. After rotary evaporation,
aqueous 2 M NaOH (50 mL) was added, and the suspension
was stirred for 1 h to remove residual dimethyl sulfate followed
by the addition of Et2O (50 mL). The layers were separated,
and the aqueous layer was washed with Et2O (50 mL). The
combined organic extracts were washed with H2O (30 mL),
dried (MgSO4), filtered, and rotary evaporated. Chromatog-
raphy (SiO2, hexanes/EtOAc, 7:3) gave dinitrile 5 (0.91 g, 93%)
as a viscous yellow oil containing a mixture of isomers. Rf :
0.55 (hexanes/EtOAc, 7:3); IR (neat): 2183, 1596, 1512, 1245,
7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(N-meth-
yltrifluoroacetamido)porphyrazine (16). Trifluoroacetic
anhydride (0.2 mL, 1.4 mmol) was added to porphyrazine 12
(8 mg, 0.013 mmol) in degassed pyridine (2 mL) at 0 °C under
Ar, and the mixture was stirred for 1 h at 0 °C. The mixture
was allowed to warm to 20 °C, ScavengePore phenethyl
piperidine (0.7-1.5 mmol/g) (1 g) was added, and then the
resulting suspension was stirred at 20 °C for 1 h. After rotary
evaporation, the residue was extracted with Et2O (20 mL) and
filtered, and then the filtrate was washed with H2O (30 mL),
saturated aqueous NaHCO3 solution (30 mL), saturated aque-
ous NH4Cl solution (30 mL), and brine (30 mL). The organic
layer was dried (MgSO4), filtered, and rotary evaporated. The
product in hexanes/EtOAc (95:5) was filtered through silica
to give amide 16 (6.2 mg, 65%) as a blue solid. Rf : 0.43
(hexanes/EtOAc, 8:2); HPLC: PHPLC ) 93%, tR ) 8.7 min; IR
(neat): 1704, 1607, 1463, 1381, 1199, 1154 cm-1; UV-vis (CH2-
Cl2) λmax (log ꢀ) 344 (4.35), 540 (3.65), 595 (3.93), 670 (3.83)
1
1026 cm-1; H NMR (400 MHz, CDCl3, δ): 0.63 (m, 1H), 1.32
(app-d, J ) 11.8 Hz, 1H), 1.47 (m, 1H), 1.91 (m, 1H), 2.54 (m,
1H), 2.68 (s, 3H), 2.78 (s, 6H), 2.84 (m, 1H), 3.03 (m, 1H), 3.54
(t, J ) 9.1 Hz, 1H), 3.69 (m, 1H), 4.05 (s, 2H), 5.97 (m, 1H),
6.17 (m, 1H), 6.84 (d, J ) 11.5 Hz, 2H), 7.13 (d, J ) 11.5 Hz,
2H); 13C NMR (125 MHz, CDCl3, δ): 29.1, 38.4, 40.2, 42.1, 42.2,
43.9, 49.4, 57.9, 71.6, 114.3, 114.6, 114.8, 114.9, 120.4, 128.4,
129.9, 132.3, 137.6, 158.9; MS (CI) m/z: 363 [M + H]+; HRMS
(CI): [M + H]+ calcd for C22H27N4O, 363.2185; found, 363.2189.
Anal. Calcd for C22H26N4O: C, 72.90; H, 7.23; N, 15.46.
Found: C, 73.20; H, 7.20; N, 15.26.
7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(meth-
ylamino)porphyrazine (12). Mg (0.22 g, 9.0 mmol), I2 (2
crystals), and 1-butanol (20 mL) were heated to reflux for 24
h under N2. The mixture was allowed to cool when dinitrile 5
(0.22 g, 0.6 mmol) and dipropylmaleonitrile 623 (0.97 g, 5.96
mmol) in 1-butanol (10 mL) were added and the was mixture
heated to reflux for another 24 h. The solvent was evaporated
under reduced pressure and formed an azeotrope with PhMe
(2 × 50 mL). The residue was preabsorbed onto silica, and the
solids were extracted with hexanes/EtOAc (8:2) until the
intensity of the initial blue color had decreased and elution of
a purple pigment had begun. The combined extracts were
rotary evaporated, and the residue was dissolved in degassed
CH2Cl2 (2 mL) under N2. Cross-linker 11(15.3 mg, 0.07 mmol)
in CH2Cl2 (0.5 mL) was added followed by catalyst 10 (5.0 mg,
6.0 µmol), and the mixture was heated to 40 °C for 12 h. CH2-
Cl2 (2 mL), MeCN (1 mL), and ethyl vinyl ether (1 mL) were
added, and the mixture was heated to 40 °C for 1 h. The gel
was filtered and washed sequentially with CH2Cl2 (3 × 20 mL)
and further extracted with CH2Cl2 (Soxhlet) for 12 h. This left
the insoluble ROM polymer (9, 0.11 g) as a blue solid. A
degassed solution of 10% trifluoroacetic acid in CH2Cl2 (5 mL)
was added to a suspension of ROM polymer 9 (0.11 g) under
Ar, and the suspension was shaken for 1 h. The resulting
mixture was filtered into H2O (20 mL), and the resulting layers
were separated. The organic layer was washed with saturated
aqueous NaHCO3 (30 mL), dried (MgSO4), filtered, and rotary
evaporated. The solution of the cleavage product was filtered
though silica with further extraction (hexanes/EtOAc, 9:1) to
give diamine 12 (61 mg, 16%) as an unstable purple solid,
which was used immediately. Rf : 0.80 (hexanes/EtOAc, 1:1.5);
UV-vis (hexanes/EtOAc, 9:1) λmax 338, 549, 595, 625, 652 nm;
MS (FAB) m/z: 638 [M+•]; HRMS (FAB): [M+•] calcd for
C37H54O10, 638.4533; found, 638.4502.
1
nm; H NMR (500 MHz, CDCl3, δ): -1.61 (br s, 2H), 1.16-
1.33 (m, 18H), 2.30 (m, 12H), 3.76 (m, 4H), 3.93 (m, 11H), 4.14
(s, 6H); 13C NMR (125 MHz, CDCl3, δ): 14.5, 14.7, 25.2, 25.3,
25.4, 25.5, 27.7, 28.0, 28.1, 28.2, 29.7, 41.6, 43.2, 112.6, 115.7,
118.2, 139.6, 141.0, 142.0, 142.4, 144.0, 144.4, 144.6, 145.3,
145.3, 147.4, 149.5, 153.4, 159.9, 160.1, 161.4, 163.6; MS (FAB)
m/z: 735 [M+•]; HRMS (FAB): [M+•] calcd for C39H53F3N10O,
734.4356; found, 734.4371.
[7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(N-
methylacetamido)porphyrazinato]zinc(II) (17). A mixture
of porphyrazine 15 (2.2 mg, 0.003 mmol) and Zn(OAc)2‚2H2O
(1 mg, 0.005 mmol) in dry DMF (2 mL) was heated to 80 °C
for 16 h under N2. Rotary evaporation and chromatography
(SiO2, hexanes/EtOAc, 1:1) gave porphyrazine 17 (2.0 mg, 83%)
as a turquoise solid. Rf : 0.47 (hexanes/EtOAc, 1:1); IR
(neat): 1674, 1603, 1463, 1148, 1082 cm-1; UV-vis (CH2Cl2)
λmax (log ꢀ) 342 (4.55), 508 (3.73), 626 (4.25) nm; 1H NMR (500
MHz, pyridine-d5, δ): 1.28-1.39 (m, 18H), 2.35 (s, 3H), 2.48
(m, 12H), 3.94-4.12 (m, 21H); 13C NMR (125 MHz, pyridine-
d5, δ): 14.8, 15.0, 23.1, 25.9, 26.0, 28.4, 28.7, 39.2, 42.8, 106.4,
118.2, 142.5, 143.2, 143.6, 144.0, 144.2, 144.9, 148.6, 151.2,
156.7, 157.0, 158.9, 159.5, 160.4, 173.2; MS (FAB) m/z: 744
[M+•]; HRMS (FAB): [M+•] calcd for C39H54N10OZn, 742.3773;
found, 742.3768.
[7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(meth-
yltrifluoroacetamido)porphyrazinato]-zinc(II) (18). Por-
phyrazine 16 (6.0 mg, 0.0082 mmol), Zn(OAc)2‚2H2O (2.5 mg,
0.011 mmol), and dry DMF (2 mL) were heated to 80 °C for
16 h under N2. The solvent was rotary evaporated, and the
product was chromatographed (SiO2, hexanes/EtOAc, 7.5:2.5)
to give porphyrazine 18 (5.0 mg, 76%) as a turquoise solid.
Rf : 0.79 (hexanes/EtOAc, 7:3); IR (neat): 1703, 1678, 1597,
1462, 1210, 1152 cm-1; UV-vis (CH2Cl2) λmax (log ꢀ) 342 (4.20),
490 (3.26), 630 (3.94) nm; 1H NMR (500 MHz, pyridine-d5, δ):
1.29-1.38 (m, 18H), 2.44 (m, 12H), 3.91-4.14 (m, 21H); 13C
NMR (125 MHz, pyridine-d5, δ): 14.8, 15.0, 25.8, 26.0, 28.3,
28.6, 41.9, 42.9, 112.6, 142.5, 143.2, 143.6, 144.2, 145.0, 156.8,
7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(N-meth-
ylacetamido)porphyrazine (15). Ac2O (0.05 mL, 0.53 mmol)
was added to porphyrazine 12 (7.5 mg, 0.012 mmol) in
degassed pyridine (2 mL) under N2, and the mixture was
heated at reflux for 18 h. The mixture was allowed to cool,
ScavengePore phenethyl piperidine (0.7-1.5 mmol/g) (1 g) was
2800 J. Org. Chem., Vol. 70, No. 7, 2005

Synthesis of Novel Unsymmetrical Porphyrazines
157.0, 159.1, 159.6, 160.5; MS (FAB) m/z: 796 [M+•]; HRMS
(FAB): [M+•] calcd for C39H51F3N10OZn, 796.3491; found,
796.3528.
30 min. The mixture was allowed to warm to 20 °C, stirred
for 18 h, and rotary evaporated. NaOH (2 M, 50 mL) was
added, and the suspension was stirred for 1 h to hydrolyze
residual dimethyl sulfate. Et2O (50 mL) was added, the layers
were separated, and then the aqueous layer was washed with
Et2O (50 mL). The combined organic extracts were washed
with H2O (30 mL), dried (MgSO4), filtered, and rotary evapo-
rated. Chromatography (SiO2, hexanes/EtOAc, 8:2) gave dini-
trile 22 (1.67 g, 76%) as a viscous orange oil containing a
mixture of isomers. Rf : 0.40 (hexanes/EtOAc, 8:2); IR (neat):
2184, 1597, 1512, 1247, 1175, 1023 cm-1; 1H NMR (500 MHz,
CDCl3, δ): 0.62 (m, 2H), 1.22-1.31 (m, 2H), 1.49 (m, 2H), 1.92
(m, 2H), 2.54 (m, 2H), 2.69 (s, 6H), 2.85 (m, 2H), 3.04 (m, 2H),
3.54 (t, J ) 9.2 Hz, 2H), 3.69 (m, 2H), 4.11 (s, 4H), 5.96 (m,
2H), 6.18 (m, 2H), 6.82 (m, 4H), 7.05 (m, 4H); 13C NMR (125
MHz, CDCl3, δ): 29.1, 38.4, 40.1, 42.2, 43.9, 49.4, 58.1, 71.6,
114.7, 114.9, 117.6, 127.9, 129.7, 132.3, 137.6, 158.9; MS (FAB)
m/z: 561 [M+•]; HRMS (FAB): [M+•] calcd for C36H40N4O2,
560.3151; found, 560.3194.
[7,8,12,13,17,18-Hexapropyl-2-(dimethylamino)-3-(meth-
ylacetamido)-2-seco-2,3-dioxoporphyrazinato]zinc(II) (19).
Porphyrazine 17 (2.0 mg, 2.7 µmol) in CH2Cl2 (40 mL) was
stirred in air for 3 days. Rotary evaporation and chromatog-
raphy (SiO2, hexanes/EtOAc, 1:1) gave seco-porphyrazine 19
(1.1 mg) and unreacted porphyrazine 17 (0.9 mg). Recovered
porphyrazine 17 was resubjected to the reaction conditions for
another 5 days, and then the solution was rotary evaporated
and chromatographed (SiO2, hexanes/EtOAc, 1:1). In total, this
gave seco-porphyrazine 19 (1.8 mg, 86%) as a magenta solid.
Rf : 0.61 (hexanes/EtOAc, 1:1); IR (neat): 1706, 1673, 1600,
1492, 1461, 1259, 1081 cm-1; UV-vis (CH2Cl2) λmax (log ꢀ) 341
(4.10), 357 (4.09), 572 (3.86), 651 (3.98) nm; 1H NMR (500 MHz,
pyridine-d5, δ): 0.89 (m, 6H), 1.17-1.50 (m, 22H), 1.71 (m,
2H), 2.21 (m, 1H), 2.46 (m, 3H), 2.81 (s, 3H), 3.45 (s, 3H), 3.77
(m, 1H), 3.97 (m, 6H), 4.20 (s, 3H), 3.39 (m, 4H); 13C NMR
(125 MHz, pyridine-d5, δ): 11.1, 14.2, 14.8, 15.0, 23.2, 24.1,
25.8, 26.0, 27.3, 28.0, 28.5, 28.6, 29.2, 30.0, 30.7, 34.0, 35.2,
39.1, 39.5, 68.3, 129.3, 131.5, 133.2, 141.7, 142.1, 143.0, 143.2,
145.1, 145.3, 152.3, 155.1, 156.0, 156.7, 157.0, 157.3, 167.9,
169.7, 171.2, 174.4; MS (FAB) m/z: 774 [M+•]; HRMS (FAB):
[M+H] calcd for C39H55N10O3Zn, 775.3750; found, 775.3778.
7,8,12,13,17,18-Hexapropyl-2,3-bis(N-methyltrifluoro-
acetamido)porphyrazine (26). Mg (0.12 g, 5.1 mmol), I2 (2
crystals), and 1-butanol (20 mL) were heated to reflux for 24
h under N2. The mixture was allowed to cool, dinitrile 22 (0.19
g, 0.34 mmol) and dipropylmaleonitrile 623 (0.55 g, 3.40 mmol)
in 1-butanol (10 mL) were added, and then the mixture was
heated to reflux for another 24 h. The solvent was removed
by rotary evaporation and subsequent azeotrope with PhMe
(2 × 50 mL). The residue was preabsorbed onto silica and
added to additional silica, which was washed extensively with
hexanes/EtOAc (8:2) until the intensity of the initial blue color
had decreased and elution of a purple pigment had begun.
After rotary evaporation, the residue was dissolved in degassed
CH2Cl2 (2 mL) under N2, cross-linker 11 (10.0 mg, 0.038 mmol)
in CH2Cl2 (0.5 mL) was added followed by catalyst 10 (3.0 mg,
3.4 µmol), and then the mixture was heated to 40 °C for 12 h.
CH2Cl2 (2 mL), MeCN (1 mL), and ethyl vinyl ether (1 mL)
were added, and the mixture was further heated to 40 °C for
1 h. The gel was filtered off and washed sequentially with CH2-
Cl2 (3 × 20 mL) and further extracted with CH2Cl2 (Soxhlet)
for 12 h to leave the insoluble ROM polymer (23, 70 mg) as a
blue solid. Degassed 1 M trifluoromethanesulfonic acid and 2
M trifluoroacetic acid in CH2Cl2 (3 mL) were added to a
suspension of ROM polymer 23 (70 mg) under Ar, which was
shaken at 20 °C for 1 h. The resulting mixture was filtered
into H2O (20 mL), and the resulting layers were separated.
The organic layer was washed with saturated aqueous NaH-
CO3 solution (30 mL), dried (MgSO4), filtered, and rotary
evaporated to give diamine 24 as a crude, unstable purple
solid, which was used immediately. Trifluoroacetic anhydride
(0.05 mL, 0.35 mmol) was added to porphyrazine 24 in
degassed pyridine (2 mL) at 0 °C under Ar and stirred for 10
min at 0 °C. The mixture was poured into saturated aqueous
NH4Cl solution (20 mL) and extracted with EtOAc (30 mL).
The organic layer was washed with saturated aqueous NH4Cl
solution (3 × 20 mL) to remove the pyridine and was dried
(MgSO4), filtered, and rotary evaporated. Chromatography
(SiO2, hexanes/EtOAc, 9:1) gave a mixture of monosubstituted
porphyrazine 25 and disubstituted porphyrazine 26. Por-
phyrazine 25:(6.2 mg). Rf : 0.33 (hexanes/EtOAc, 9:1); IR
(neat): 1697, 1650, 1463, 1193, 1144, 1086 cm-1; UV-vis (CH2-
2-[4-(Bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzylamino]-
3-([4-(bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzylidene]-
amino)but-2-enedinitrile (20). TFA (2 drops) was added to
amine 4 (1.71 g, 5.3 mmol) and aldehyde 2 (1.27 g, 5.3 mmol)
in MeOH (10 mL). After 2 h, the yellow precipitate was filtered
off and washed with Et2O (10 mL) to give imine 20 (2.53 g,
90%) as a yellow solid containing a mixture of isomers, which
was insoluble in most organic solvents and was used without
further purification: mp 177-179 °C; IR (neat): 2229, 2199,
1
1602, 1512, 1250, 1165 cm-1; H NMR (500 MHz, DMSO-d6,
δ): 0.58 (m, 2H), 1.24 (m, 2H), 1.37 (m, 2H), 1.87 (m, 2H), 2.50
(m, 2H, obscured by DMSO), 2.80 (m, 2H), 2.94 (m, 2H), 3.50
(t, J ) 9.0 Hz, 1H), 3.59 (t, J ) 9.0 Hz, 1H), 3.65 (m, 1H), 3.75
(m, 1H), 4.48 (d, J ) 6.4 Hz, 2H), 5.93 (m, 2H), 6.17 (m, 2H),
6.90 (d, J ) 9.0 Hz, 2H), 6.98 (d, J ) 9.0 Hz, 2H), 7.23 (d, J )
9.0 Hz, 2H), 7.95 (d, J ) 9.0 Hz, 2H), 8.20 (m, 1H), 8.43 (m,
1H); 13C NMR (125 MHz, DMSO-d6, δ): 28.6, 38.1, 41.6, 43.4,
48.4, 48.9, 71.1, 71.3, 103.6, 113.3, 113.7, 114.6, 114.7, 127.0,
128.1, 128.4, 130.4, 131.0, 132.1, 137.4, 155.0, 158.1, 161.7;
MS (FAB) m/z: 531 [M+•]; HRMS (FAB): [M+•] calcd for
C34H34N4O2, 530.2682; found, 530.2678.
2,3-Bis-[4-(bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzyl-
amino]but-2-enedinitrile (21). NaBH4 (0.47 g, 12.4 mmol)
was added in portions to a suspension of imine 20 (2.2 g, 4.15
mmol) in dry THF (23 mL) and MeOH (15 mL) under N2. The
slurry was stirred for 2 h and poured into ice/H2O (150 mL),
and then the sticky residue was filtered, redissolved in THF
(30 mL), and washed through the filter with additional THF.
After rotary evaporation, residual H2O was removed by
azeotrope with PhMe (2 × 30 mL) to leave diamine 21 (2.18 g,
99%) as a brown oil containing a mixture of isomers, which
was used without further purification. IR (neat): 2203, 1607,
1512, 1247, 1175 cm-1; 1H NMR (500 MHz, DMSO-d6, δ): 0.58
(m, 2H), 1.24 (m, 2H), 1.37 (m, 2H), 1.87 (m, 2H), 2.50 (m, 2H,
obscured by DMSO), 2.80 (br s, 2H), 2.95 (br s, 2H), 3.49 (t, J
) 9.0 Hz, 2H), 3.65 (m, 2H), 4.15 (d, J ) 6.0 Hz, 4H), 4.48 (m,
2H), 5.94 (m, 2H), 6.18 (m, 2H), 6.85 (d, J ) 8.6 Hz, 4H), 7.12
(d, J ) 8.6 Hz, 4H); 13C NMR (125 MHz, DMSO-d6, δ): 28.7,
37.8, 41.7, 43.4, 48.4, 48.9, 71.0, 109.8, 114.4, 115.4, 128.7,
131.0, 132.1, 137.3, 158.0; MS (FAB) m/z: 533 [M+•]; HRMS
(FAB): [M-H]+ calcd for C34H35N4O2, 531.2760; found, 531.2763.
1
Cl2) λmax: 344, 586, 680 nm; H NMR (500 MHz, pyridine-d5,
δ): -1.15 (s, 2H), 1.01 (t, J ) 7.5 Hz, 3H), 1.25-1.38 (m, 15H),
2.15 (sextet, J ) 7.5 Hz, 2H), 2.41 (m, 10H), 3.68 (d, J ) 5.3
Hz, 3H), 3.76 (t, J ) 7.5 Hz, 2H) 3.88-4.01 (m, 10H), 4.10 (s,
3H), 9.48 (q, J ) 5.3 Hz, 1H); 13C NMR (125 MHz, pyridine-
d5, δ): 14.5, 14.7, 15.0, 25.7, 25.8, 25.9, 27.5, 27.9, 28.3, 28.5,
30.0, 30.5, 41.5, 139.9, 141.9, 142.0, 142.7, 144.0, 144.9, 145.3,
145.7, 146.7, 147.0, 161.8, 163.9; MS (FAB) m/z: 720 [M+•];
HRMS (FAB): [M+•] calcd for C38H51F3N10O, 720.4199; found,
720.4199. Disubstituted porphyrazine 26 (7.3 mg): Rf : 0. 78
(hexanes/EtOAc, 9:1); HPLC: PHPLC ) 100%, tR ) 7.1 min; IR
(neat): 1704, 1463, 1263, 1151, 1081 cm-1; UV-vis (CH2Cl2)
2,3-Bis-{[4-(bicyclo[2.2.1]hept-5-en-2-ylmethoxy)benzyl]-
methylamino}but-2-enedinitrile (22). Dinitrile 21 (2.1 g,
3.94 mmol) in dry THF (20 mL) was added to NaH (0.4 g, 9.85
mmol, 60% suspension in mineral oil) in dry THF (50 mL) at
-30 °C under N2. The mixture was allowed to warm to -10
°C, and dimethyl sulfate (0.82 mL, 8.67 mmol) was added over
J. Org. Chem, Vol. 70, No. 7, 2005 2801

Fuchter et al.
λmax (log ꢀ) 340 (4.16), 546 (3.55), 586 (4.08), 616 (4.01) nm; 1H
NMR (500 MHz, pyridine-d5, δ): -2.24 (s, 2H), 1.32-1.39 (m,
18H), 2.46 (m, 12H), 3.91-4.10 (m, 18H); 13C NMR (125 MHz,
pyridine-d5, δ): 14.9, 15.0, 25.8, 28.2, 28.5, 28.7, 39.9, 68.2,
116.3, 118.6, 129.3, 131.5, 142.7, 143.7, 145.6, 147.2, 148.1,
28.6, 30.7, 41.6, 142.3, 143.1, 143.8, 144.2, 144.9, 156.4, 156.6,
158.2, 158.6, 159.1, 160.7; MS (FAB) m/z: 784 [M+•]; HRMS
(FAB): [M+•] calcd for C38H49F3N10OZn, 782.3334; found,
782.3309.
158.6, 166.8; MS (FAB) m/z: 817 [M+•]; HRMS (FAB): [M+•
]
Acknowledgment. We thank Glaxo SmithKline for
the generous endowment (to A.G.M.B.), the Royal
Society and the Wolfson Foundation for a Royal Society
Wolfson Research Merit Award (to A.G.M.B.), the Wolf-
son Foundation for establishing the Wolfson Centre for
Organic Chemistry in Medical Sciences at Imperial
College, the Engineering and Physical Sciences Re-
search Council, the National Science Foundation, and
Schering AG for generous support of our studies. We
additionally thank Dr. Klaus Suhling and Miss Carolyn
Jones for the loan of the equipment and assistance in
the measurement of the fluorescence decays.
calcd for C40H50F6N10O2, 816.4022; found, 816.4016. Porphyra-
zine 25 (6.2 mg) was resubjected to the above reaction
acylation conditions for 1 h at 0 °C. Following an analogous
workup and filtration through silica (hexanes/EtOAc, 9:1),
additional porphyrazine 26 (6.6 mg) was isolated. In total, this
gave porphyrazine 26 (13.9 mg, 5%) as a violet solid.
[7,8,12,13,17,18-Hexapropyl-2-(methylamino)-3-(meth-
yltrifluoroacetamido)porphyrazinato]-zinc(II) (27). Por-
phyrazine 26 (10.3 mg, 0.0126 mmol), Zn(OAc)2‚2H2O (3.9 mg,
0.018 mmol), and dry DMF (2 mL) were heated to 80 °C for
16 h under N2. Rotary evaporation and chromatography (SiO2,
hexanes/EtOAc, 8:2) gave porphyrazine 27 (8.0 mg, 72%) as a
turquoise solid. Rf : 0.35 (hexanes/EtOAc, 8:2); IR (neat): 1698,
1633, 1462, 1248, 1149, 1018 cm-1; UV-vis (CH2Cl2) λmax (log
1
ꢀ) 341 (4.62), 572 (4.05), 617 (4.46), 644 (4.29) nm; H NMR
Supporting Information Available: General experimen-
tal procedures and structural data for all new compounds. This
material is available free of charge via the Internet at
http://pubs.acs.org.
(500 MHz, pyridine-d5, δ): 1.04 (t, J ) 7.3 Hz, 3H), 1.24-1.37
(m, 15H), 2.22 (sextet, J ) 7.3 Hz, 2H), 2.49 (m, 10H), 3.73 (d,
J ) 5.3 Hz, 3H), 3.80 (t, J ) 7.3 Hz, 2H) 3.91-4.05 (m, 10H),
4.09 (s, 3H), 9.17 (q, J ) 5.3 Hz, 1H); 13C NMR (125 MHz,
pyridine-d5, δ): 14.6, 14.8, 15.0, 25.7, 25.9, 26.0, 28.1, 28.3,
JO047792Q
2802 J. Org. Chem., Vol. 70, No. 7, 2005