A 'push-pull' tropylium-fused aminoporphyrazine

Article abstract of DOI:10.1016/j.tet.2009.09.105

Crossover Linstead macrocyclization of cycloheptatrienylmaleonitrile and (dimethylamino)-maleonitrile gave access to an unsymmetrical (A₃B) porphyrazine bearing six peripheral amino substituents and a fused cycloheptatrienyl ring. Subsequent hy

Full text of DOI:10.1016/j.tet.2009.09.105

Tetrahedron 65 (2009) 9690–9693
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Tetrahedron
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A ‘push–pull’ tropylium-fused aminoporphyrazine
Andrea Ruggiero a, Matthew J. Fuchtera, Okanya J. Kokas a, Mihaela Negru a, Andrew J.P. White a,
,
Peter R. Haycock a, Brian M. Hoffman b, Anthony G.M. Barrett a
*
a Department of Chemistry, Imperial College, London SW7 2AZ, England, UK
b Department of Chemistry, Northwestern University, Evanston, IL 60208, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 July 2009
Accepted 24 September 2009
Available online 30 September 2009
Crossover Linstead macrocyclization of cycloheptatrienylmaleonitrile and (dimethylamino)-maleonitrile
gave access to an unsymmetrical (A3B) porphyrazine bearing six peripheral amino substituents and
a fused cycloheptatrienyl ring. Subsequent hydride abstraction gave a tropylium-fused aminoporphyr-
azine, which contains both strongly electron-donating and withdrawing groups and thus can be labelled
as a ‘push–pull’ macrocycle. Detailed structural studies of this novel porphyrazine are described.
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
bearing an electron-donating group on one side of the molecule
and an electron-withdrawing group on the other have been termed
Over the past few decades, considerable research in the field of
non-linear optics (NLO) has been reported1–3 due in part to the
applicability of NLO materials in telecommunications and optical
signal processing devices.2,3 Since the mid-1980s organic NLO
materials have emerged as important targets, since they exhibit
large and fast nonlinearities and are, in general, easy to process and
integrate into optical devices.4–6 Of particular importance is the fact
that fine-tuning of the NLO properties can be achieved by rational
modification of the chemical structure. Amongst the various po-
tential NLO chromophores, tetrapyrrolic macrocycles occupy
a unique position.7–9 Their ground state absorption is mostly con-
fined to a few narrow regions (Soret and Q bands) allowing high
transmission in the spectral window between these bands. More-
over, their optical properties can be readily varied by altering the
cavity metal, its oxidation state or axial ligands, or the nature of the
substituents at the periphery. While porphyrins and phthalocya-
nines have been extensively examined in this regard, the related
tetraazaporphyrins (porphyrazines, pz) have not.
‘push–pull’, and such systems have received special attention, due
to the need for a molecular dipole for efficient NLO properties.8,9
We considered that amino-porphyrazines ring fused to a tropylium
cation should be interesting targets with potential NLO properties
(see 1, Fig. 1).
2. Results and discussion
Our initial attempts to synthesize a ‘push–pull’ porphyrazine 1
bearing an unsubstituted tropylium ring (R2¼H), were largely un-
successful. During the course of this work however, Kobayashi and
co-workers published the synthesis of porphyrazine 2 (Fig. 1).20
Subsequent oxidation of porphyrazine 2 using DDQ was accom-
panied by spectroscopic changes (UV–vis, MS, MCD) consistent
with the formation of mono-tropylium species. In light of this
precedent, we examined the synthesis of porphyrazine 1 (R2¼Ph),
so as to fully characterize a porphyrazine tropylium cation. Cyclo-
hepatrienyl maleonitrile 11 was prepared by the Kobayashi route,20
Porphyrazines are porphyrin analogues, with meso nitrogen
atoms replacing the meso carbon atoms. Peripheral heteroatom
functionalization of the macrocycle by thiols, amines or alcohols
results in significant modulation of their physical and electronic
properties.10–13 Of particular note, porphyrazines containing pe-
ripheral amino substituents show strong electron donation into the
Ph
Ph
X
R2
R2
N
N
N
Ph
Ph
Ph
Ph
N
Mg
N
N
N
N
N
N
N
Mg
N
NR1
NR1
R12N
R12N
2
2
N
macrocyclic
p
-system11,13,14 and numerous structural analogues,15
metallic complexes,15c,16 charge transfer complexes,17 and seco-
porphyrazines have been prepared.18,19 Tetrapyrrolic macrocycles
N
N
N
2
1
R12N
NR1
2
Ph
Ph
* Corresponding author. Tel.: þ44 20 759 45767; fax: þ44 20 759 45805.
E-mail address: agm.barrett@imperial.ac.uk (A.G.M. Barrett).
Figure 1. Generic target porphyrazine 1 and Kobayashi’s system.20
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.105

A. Ruggiero et al. / Tetrahedron 65 (2009) 9690–9693
9691
N
N
Ph
Ph
d
3
2
a
c
N
N
N
N
P2O5
N N
Ph
Ph
2
NaMnO4
NH3
Ph
Ph
2
2
3
10
1
1
3
2
Δf
3
2
RO2C
CO2R
H2NOC
CONH2
NC
CN
7
NC
CN
3
6
11
N
N
N
M
N
4
:
R = H
HCl,
MeOHb
N2
NMe2
NMe2
g
Me2N
Me2N
Mg(OBu)2
N
N
5
: R = Me
NC
Me2N
CN
NMe2
c
N
N
NH3
H2O2
N
N
N N
Me2N
NMe2
12
Ethyl pyruvatee
13: M = Mg
14: M = 2H
EtO2C
CO2Et
8
AcOHh
9
Reagents and conditions:
(a) NaMnO4, NaOH, Δ, 12 h, 65%; (b) HCl, MeOH, rt, 12 h, 25%; (c) NH3, MeOH, rt, 4 d, 75-96%; (d) P2O5, reflux, 5 h, 54%;
n
(e) H2O2, Ethyl pyruvate, 30 min, 22%; (f) PhCl, Δ, 16 h, 36%; (g) Mg(O Bu)2, n-BuOH, Δ, 24 h, 9%; (h) AcOH, CH2Cl2, rt, 72%.
Scheme 1.
involving cycloaddition21 of 1,2-diphenylpropene (10)20,22 with
4,5-dicyanopyrazine (7). Oxidative cleavage of phthalazine (3)
furnished diacid 4 in moderate yield (65%).24 Following the pro-
cedure of Di Stefano et al.,23 esterification of 4 in the presence of HCl
and MeOH, followed by reaction with ammonia gave diamide 6.
Alternatively and more conveniently, radical carboxylation of pyr-
idazine (8)25 and amidation gave diamide 6. Dehydration of di-
amide 6 using phosphorus pentaoxide gave dicyanopyrazine 7 in
moderate yield (54%). Cycloaddition of dinitrile 7 with 1,2-diphe-
nylpropene (10)20,22 and nitrogen elimination21 gave maleonitrile
11 (Scheme 1).
Titration of porphyrazine 13 in dichloromethane and methanol
with Ph3CX (X¼BF4, PF6) resulted in notable changes in the UV–vis
spectrum (Fig. 2). The broad Q band centred around 710 nm11 un-
dergoes further broadening with a decrease in intensity. In addi-
tion, the small band at 550 nm, attributed to n–
*
p transitions of the
nitrogen lone pairs,11 disappears and the Soret band undergoes
a blue shift with a decrease in intensity. Of particular importance is
the development of a new peak around 811 nm that overlaps with
the Q band. In the DDQ oxidation of porphyrazine 2 by Kobayashi
and co-workers,20 a new peak was observed at 820 nm, and at-
tributed to expansion of the
p-system. Despite containing signifi-
A statistically-biased crossover Linstead macrocyclization11 of
maleonitriles 11 and 1226 in a 1:7 ratio, respectively, afforded the
crude target unsymmetrical (A3B) porphyrazine, amongst a mix-
ture of other porphyrazine constituents (A4, A2B2). Purification by
chromatography gave the A3B cyclohepatrienyl fused amino-
porphyrazine 13 in a relatively low yield (9%) (Scheme 1). It should
be noted however that this yield is comparable to other challenging
mixed macrocyclizations of the electron-rich amino maleoni-
triles.11 Demetallation of porphyrazine 13 proceeded unremarkably
to give free-base porphyrazine 14 in good yield (72%).
cantly less conjugation than 2, the new peak of 13 is only slightly
blue-shifted in comparison. This is a result of the previously
reported influence of the strongly electron-donating peripheral
amino substituents, which strongly modulate the Q band shift.11
Analogous titration studies performed on H2[pz(A3B)] 14 (see
Supplementary data) reveal a slight blue shift and broadening of
the Soret band, with a decrease in intensity of the bands at 539 nm
and 719 nm and a new peak emerging at 820 nm.
While our titration studies compared favourably with Kobaya-
shi’s result, we were keen to unequivocally characterize tropylium
porphyrazines instead of just relying upon UV–vis, MS, and MCD
studies.20 Slow evaporation of a THF and dichloromethane (1:1)
solution of porphyrazine 13 with triphenylmethyl hexa-
fluorophosphate under anhydrous, anaerobic conditions, provided
crystals suitable for an X-ray crystallographic study (Fig. 3). This is
the first example an X-ray crystallographic structure of a tropylium
cation fused to any macrocycle of the porphyrin/phthalocyanine/
porphyrazine class. Curiously the structure revealed the free-base
We considered that, although Kobayashi20 and Latos–Gra-
zynski27 utilized DDQ for the oxidation of cycloheptatriene-por-
phyrazine
2 and carbocyclic porphyrin analogues to the
corresponding tropylium species, respectively, hydride abstraction
of porphyrazine 13 or 14 using triphenylmethyl tetrafluoroborate or
hexafluorophosphate28 would be more convenient, in that it should
directly provide tropylium-fused porphyrazines with a chemically
inert, non-coordinating counterion, which should aid product iso-
lation and characterization (Scheme 2).
23
Ph
Ph
X
32
31
22
21
3
2
N
N
N
M
N
-
X
Ph3C+
NMe2
NMe2
Me2N
Me2N
13 or 14
N
N
N
N
X = BF4, PF6
Me2N
NMe2
15: M= Mg
16: M = 2H
Scheme 2.
Figure 2. UV–vis changes upon Ph3CBF4 addition to porphyrazine 13.

9692
A. Ruggiero et al. / Tetrahedron 65 (2009) 9690–9693
Since tropylium porphyrazine 16 was designed as a ‘push–pull’
system, it is reasonable to expect to see shortening of the N–C(pz)
bond lengths, corresponding to a slight increase in bond order, due
to the electron density from the nitrogen (NMe2) lone pairs
‘pushing’ into the ring. Indeed, statistically significant shortening of
the C(pz)–N bond lengths (0.016–0.042 Å) are visible for three of
the six dimethylamino groups (Table S1): N(53)–C(19), N(44)–
C(13), and N(38)–C(8). This effect is partially reflected in changes
throughout the porphyrazine skeleton. As can be seen in Figure 3,
the N(38), N(44) and N(53)-bound NMe2 units of 16 are approxi-
mately co-planar with respect to their parent pyrrole, whilst the
others are significantly inclined. It is therefore possible to correlate
the bond shortening, and thus electron donation, to the dimethy-
lamino groups whose lone pairs are co-planar with the
p system.
We have previously demonstrated, that due to conflicting non-
bonding interactions, both dimethylamino groups on a single pyr-
role unit cannot be co-planar and thus both efficiently donate
electron density simultaneously.30 It is therefore not surprising that
in structure 16 (Fig. 3b), only three of the possible six amino sub-
stituents appear to be involved in electron donation.
An analytically pure sample of porphyrazine 16 was isolated by
chromatography and characterized by NMR spectroscopy. Com-
parison of the 1H NMR spectra of porphyrazines 13 and 16 dem-
onstrated a downfield shift of the olefinic protons (21, 31, see
Schemes 1 or 2 for numbering) from 9.26 ppm in 13 to 10.09 ppm in
16, supporting an increase in p-conjugation. While the methylene
protons (23, see Schemes 1 or 2 for numbering, 4.21 ppm) in 13 were
absent in the spectrum of 16, the location of the corresponding
methine proton was not immediately apparent but shown to be at
8.8 ppm in a 1D TOCSY experiment (see Supplementary data).
In conclusion, a method for the synthesis of a tropylium-fused
aminoporphyrazine 15 has been described. An X-ray crystallo-
graphic study and NMR spectroscopy of the free-base derivative 16,
as compared to the starting material from which it is derived, gave
unambiguous confirmation of the proposed structure, and also
indicated electron donation from three of the six peripheral amino
substituents. This confirms the proposition of porphyrazine 15 as
a ‘push–pull’ macrocycle.
Figure 3. The molecular structure of porphyrazines (a) 14 and (b) 16þ
.
(not magnesium) tropylium porphyrazine salt 16 crystallized from
the mixture. Further isolation studies (vide infra) confirmed that
exposure of magnesium porphyrazine 13 to triphenyl carbonium
salts results in partial demetallation and subsequent decomposition
of the macrocycle. As a point of comparison, we also determined the
X-ray crystal structure of the neutral porphyrazine 14 (Fig. 3).
On oxidation of the porphyrazine 14 to the tropylium porphyr-
azine 16, the change in the fused seven- and five-membered ring
system is clearly visible (Fig. 3). The C(23) methylene group in 14
has become a methine in 16,29 resulting in a near planar geometry
for the 10-membered ring in 16, with C(22), C(23) and C(24) lying
only ca. 0.07, 0.18 and 0.11 Å, respectively, out of the plane of the
other seven atoms. This contrasts with the significantly folded ge-
ometry seen for the 10-membered ring in 14, where C(22), C(23)
and C(24) lie ca. 0.43, 1.27 and 0.40 Å out of the plane of the
remaining seven atoms. Whilst the pattern of bonding within the
10-membered ring system of both structures possess approximate
C2 symmetry about the N(2)/C(23) axis, the effect of the change in
the bonding at C(23) between 14 and 16 can be seen almost
throughout the 10-membered ring. The overall effect on going from
14 to 16 is one of increasing delocalization; the C(2)–C(3)/C(5)–C(4)
bonds become ca. 0.02 Å shorter, the C(3)–C(21)/C(4)–C(25) bonds
become ca. 0.06 Å shorter, the C(21)–C(22)/C(24)–C(25) bonds be-
come ca. 0.05 Å longer, and the C(22)–C(23)/C(25)–C(23) bonds
become ca. 0.10 Å shorter (see Table S1 in Supplementary data). The
C(3)–C(4) bond, common to the seven- and five-membered ring
systems that are fused together, is ca. 0.05 Å longer, whilst the
bonds to N(2) are unchanged.
3. Experimental
3.1. General
3.1.1. Mg[pz(A3B)] (13). A slurry of Mg (180 mg, 7.4 mmol) and I2
(ca. 2 crystals) in n-BuOH (20 mL) was heated to reflux for 24 h. The
mixture was allowed to cool to room temperature when dinitriles
12 (492 mg, 3.0 mmol) and 11 (126 mg, 0.43 mmol) in n-BuOH
(12 mL) were added and the mixture heated to reflux for a further
24 h. The mixture was filtered through Celite and the solids washed
with CH2Cl2. The mixture was purified by triple chromatography
(MeOH:CHCl3:Et2O 0.3:70:70); (MeOH:CH2Cl2 1:30); (MeOHE-
t2O:CH2Cl2 1:4:30) to give porphyrazine 13 (30 mg,) as a blue solid:
Rf 0.33 (MeOH:CH2Cl2 1:10); IR (neat) 3583, 3355, 3195, 1662, 1580,
1449, 1378, 1308, 1260, 1208, 1003 cmꢀ1; UV–vis (CH2Cl2) lmax
(log 3 d 3.82
) 356 (4.53), 690 (4.30); 1H NMR (500 MHz, py-d5)
(s, 12H), 3.97 (s, 12H), 4.13, (s, 12H), 4.21 (s, 2H), 7.44 (m, 2H), 7.58
(m, 4H), 8.23 (d, J¼7.5 Hz, 4H), 9.26 (s, 2H); 13C NMR (125 MHz, py-d5)
d
35.0, 43.0, 44.9, 45.5, 55.1, 122.4, 127.6, 127.9, 129.4, 131.7, 132.3,
138.0, 138.8, 142.4, 152.6, 152.7, 156.8, 157.8; MS (MALDI) m/z 812
[MþH]þ; HRMS (MALDI) calcd for C45H51MgN14: [MþH]þ, 812.28,
found: [MþH]þ, 812.96. Anal. Calcd for C45H50MgN14: C, 66.62; H,
6.21; N, 24.17. Found: C, 66.70; H, 6.30; N, 24.05.
3.1.2. H2[pz(A3B)] (14). AcOH (0.26 mL, 4.6 mmol) was added at
0 ꢁC to Mg-porphyrazine 13 (37 mg, 46
The mixture stirred at room temperature for 16 h, poured into
mmol) in CH2Cl2 (11 mL).

A. Ruggiero et al. / Tetrahedron 65 (2009) 9690–9693
9693
aqueous NaOH (1 M; 20 mL) and extracted with CH2Cl2 (3ꢂ10 mL)
References and notes
until the aqueous layer was colourless. The combined organic
extracts were dried (MgSO4), filtered and rotary evaporated.
Chromatography (MeOH:CH2Cl2 1:40) gave porphyrazine 14
(26 mg, 72%) as a purple solid: Rf 0.87 (MeOH:CH2Cl2 1:20); IR
(neat) 3583, 3356, 3193, 1658, 1631, 1596, 1424, 1379, 1311, 1207,
1. Boyd, R. W. Nonlinear Optics; Academic: San Diego, CA, 1992.
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Williams, D., Eds.; J. Wiley: New York, NY, 1991.
1081, 874 cmꢀ1; UV–vis (CH2Cl2) lmax (log
3
) 341 (4.44), 539 (4.25),
719 (4.20) nm; 1H NMR (500 MHz, py-d5)
d
3.73 (s, 12H), 3.90 (s,
12H), 4.07 (s, 12H), 4.20 (s, 2H), 7.44 (m, 2H), 7.58 (m, 4H), 8.23 (d,
6. Nonlinear Optics of Organic Molecules and Polymers; Nalwa, H. S., Miyata, S., Eds.;
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J¼7.4 Hz, 4H), 9.12 (s, 2H); 13C NMR (125 MHz, py-d5)
d 14.3, 23.0,
29.6, 30.0, 32.1, 35.1, 43.4, 45.0, 121.8, 127.7, 128.2, 129.3, 129.4, 131.7,
132.1,139.0,141.9,142.1,155.4; MS (MALDI) m/z 790 [MþH]þ; HRMS
(MALDI) calcd for C45H53N14: [MþH]þ, 789.99, found: [MþH]þ,
´
´
´
7. de la Torre, G.; Vazques, P.; Agullo-Lopez, F.; Torres, T. J. Mater. Chem. 1998, 8,
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´
´
´
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789.88. C45H52N14
.
Crystal data for 14: C45H52N14$MeCN,
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M¼830.06, triclinic, P1 (no. 2), a¼12.9108(4), b¼13.4537(5),
c¼13.6153(4) Å,
a
¼89.983(3),
b
¼68.104(3),
g
¼86.542(3)ꢁ,
V¼2189.72(13) Å3, Z¼2, Dc¼1.259 g cmꢀ3
,
m
(Cu-K
a
)¼0.626 mmꢀ1
,
Chem; Karlin, K. D., Ed.; J. Wiley
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& Sons: New York, NY, 2001; Vol. 50,
T¼173 K, deep purple blocks, Oxford Diffraction Xcalibur PX Ultra
diffractometer;
8355
independent
measured
reflections
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(Rint¼0.0361), F2 refinement, R1(obs)¼0.047, wR2(all)¼0.131, 5174
independent
observed
absorption-corrected
reflections
[jFoj>4
s
(jFoj), 2qmax¼143ꢁ], 621 parameters. CCDC 7,37,182.
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3.1.3. {2H[pz(A3B)]}PF6 (16). Ph3CPF6 (9.57 mg, 1 equiv) in CH2Cl2
(1 mL) was added to Mg[pz(A3B)] 13 (20 mg, 0.024 mmol) in CH2Cl2
(1 mL) and the reaction mixture was stirred at ambient tempera-
ture for 1 h in the dark (N2). After rotary evaporation, the residue
was triturated with dry hexane (5ꢂ1 mL). Double chromatography
(CH2Cl2:MeOH 30:1), (CHCl3:MeOH 30:1) gave H2[pz(A3B)]þPF6ꢀ 16
(5 mg, 22%) as a blue solid: Rf 0.45 (MeOH:CHCl3 110); UV–vis
(CH2Cl2) lmax 316, 544, 660, 744, 820 nm; 1H NMR (500 MHz, py-d5)
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d
3.35 (s, 12H), 3.62 (s, 12H), 3.95 (s, 12H), 7.65 (m, 2H), 7.75 (m, 4H),
8.11 (d, J¼7.5 Hz, 4H), 8.88 (s, 1H), 10.09 (s, 2H); 13C NMR (125 MHz,
py-d5)
d 30.0, 43.1, 44.3, 44.9, 45.2, 79.0, 128.0, 128.2, 128.4, 128.9,
130.1; MS (MALDI) m/z 788 [M]þ. Crystal data for 16:
(C45H51N14)(PF6)$C4H8O, M¼1005.07, triclinic, P1 (no. 2), a¼9.4257(2),
b¼15.8772(5),
c¼16.4032(5) Å,
a
¼79.931(2),
b
¼78.654(2),
g
¼86.405(2)ꢁ, V¼2368.74(12) Å3, Z¼2, Dc¼1.409 g cmꢀ3
, m(Cu-
K
a
)¼1.185 mmꢀ1, T¼173 K, very dark platy needles, Oxford Dif-
fraction Xcalibur PX Ultra diffractometer; 9067 independent
measured reflections (Rint¼0.0603), F2 refinement, R1(obs)¼0.044,
wR2(all)¼0.117, 4764 independent observed absorption-corrected
reflections [jFoj>4
s
(jFoj),
2
qmax¼143ꢁ], 678 parameters. CCDC
7,37,183.
19. (a) Montalban, A. G.; Baum, S.; Hoffman, B. M.; Barrett, A. G. M. Dalton Trans.
2003, 2093–2102; (b) Fuchter, M. J.; Hoffman, B. M.; Barrett, A. G. M. J. Org.
Chem. 2006, 71, 724–729.
Acknowledgements
20. Kobayashi, N.; Nonomura, T.; Nakai, K. Angew. Chem., Int. Ed. 2001, 40,
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We thank GlaxoSmithKline for the generous endowment (to
A.G.M.B.), the Wolfson Foundation for establishing the Wolfson
Centre for Organic Chemistry in Medical Sciences at Imperial Col-
lege, the Engineering and Physical Sciences Research Council and
the National Science Foundation for generous support of our
studies.
21. Turchi, S.; Giomi, D.; Capaccioli, C.; Nesi, R. Tetrahedron 1997, 53, 11711–11720.
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Supplementary data
General experimental methods, additional experimental pro-
cedures, compound characterization data, copies of spectra and
chromatograms, and crystallographic information files (CIFs) are
available. Supplementary data associated with this article can be
found in the online version at doi:10.1016/j.tet.2009.09.105.
29. The hydrogen atoms on C(21), C(23) and C(25) in the structures of both 14 and
16 were found in the positions shown in Figure 3 (see the Supplementary data
for more details).
30. Baum, S.; Trabanco, A. A.;Montalban, A. G.; Micallef, A. S.; Zhong, C.; Meunier, H. G.;
Suhling,K.; Philips, D.; White, A. J.P.;Williams, D. J.; Barrett,A. G.M.;Hoffman, B.M.
J. Org. Chem. 2003, 68, 1665–1670.