Dodecasubstituted metallochlorins (metallodihydroporphyrins)

Article abstract of DOI:10.1039/a708766g

Regioseleclive bromination of 2-nitro-5,10,15,20-tetra-phenylporphyrin, cyclopropa[b]chlorins, or trans-bis-(dicyanomethyl)chlorms occurs in the pyrrole subunit opposite the substituted ring; exhaustive bromination of functionalized tetraphenylchlorins pr

Full text of DOI:10.1039/a708766g

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Dodecasubstituted metallochlorins (metallodihydroporphyrins)
Kalyn M. Shea, Laurent Jaquinod, Richard G. Khoury and Kevin M. Smith*†
Department of Chemistry, University of California, Davis, CA 95616, USA
Regioselective bromination of 2-nitro-5,10,15,20-tetra-
phenylporphyrin, cyclopropa[b]chlorins, or trans-bis-
(dicyanomethyl)chlorins occurs in the pyrrole subunit oppo-
site the substituted ring; exhaustive bromination of
functionalized tetraphenylchlorins provides a route to dode-
casubstitued dihydroporphyrins for the first time.
Treatment of 2-nitroTPP 1 (2 g scale) with 2.5 equiv. of NBS
in refluxing CHCl3 afforded 2-nitro-12,13-dibromoTPP 3 in
good yield (82%). Reaction of 3 (100 mg scale) with
malononitrile (10 equiv.) and K2CO3 in THF afforded the
cyclopropyl derivative 7 in 65% yield. The 1H NMR spectrum
of 7 displayed a singlet at d 5.08, characteristic of the reduced
pyrrole protons, and two doublets at d 8.43 and 8.71. Similar
treatment of 3 at 60 °C led to a second chlorin compound, 6, in
62% yield. This set of reactions reveals the bimodal reactivity of
2-nitroTPP: (i) nucleophilic attack at the double bond bearing
the nitro group and (ii) electrophilic regiospecific attack at the
antipodal double bond (Fig. 1). The molecular structure of
compound 6 was further confirmed by X-ray crystallography
[Fig. 2(a)].‡
The existence of nonplanar hydroporphyrins in photosynthetic
chromophores is increasingly evident in X-ray structures of
protein complexes.1 A series of synthetic nonplanar porphyrin
models, obtained by steric crowding of b- and meso-positions,
has established that such conformational variations can have
significant effects on the physical and chemical properties of
nonplanar porphyrins.2,3 Results show that the excited state
properties of some of these chromophores are exquisitely
sensitive to structural and vibrational variations.4 The synthesis
of such model systems often requires the relatively inaccessible
3,4-disubstituted pyrrole for condensation with aldehydes.5
Nonplanar b-brominated porphyrins, on the other hand, are
easily accessed via controlled bromination of porphyrins6 or
metalloporphyrins,7 and have since provided intermediates for a
range of nonplanar b-arylporphyrin syntheses.8 Extension of
these synthetic efforts to hydroporphyrin systems will allow
facile entry into highly nonplanar dihydroporphyrins (chlorins)
and thus provide a means to more effectively test the theoretical
predictions9 of the consequences of nonplanar distortions in this
biologically important class of compounds.
2-Nitro-5,10,15,20-tetraphenylporphyrins have been shown
to undergo nucleophilic attack at the b–bA bond bearing the nitro
group leading to a range of b-substituted porphyrins,10 and
more recently, work completed in our laboratory has provided
new methodology for the preparation of a wide range of highly
substituted dihydroporphyrin systems by way of nucleophilic
attack of 2-nitro-5,10,15,20-tetraphenylporphyrin 1 (2-ni-
troTPP), with ‘active’ methylene compounds.11 It has also been
shown that regiospecific functionalization of pyrrolic positions
on the porphyrin periphery occurs via fixation of the delocaliza-
tion pathway.12
Ph
NO2
Ph
NO2
N
N
N
N
NH
N
N
Cu
Ph
Ph
Ph
Ph
HN
Ph
Ph
1
2
NC
CN
Ph
Ph
NO2
CN
CN
NH
N
N
NH
N
N
Ph
Br
Ph
Ph
Ph
HN
HN
Br
Ph
Ph
4
3
NC
Here we show that either a nitro group or a reduced pyrrole
substituents directs the bromination to the antipodal pyrrolic
ring, leading to 12,13-dibromoporphyrin products. We also
demonstrate that, via hexabromination of metallated dihy-
droporphyrins, highly nonplanar dodecasubstitued dihydropor-
phyrins can be prepared for the first time.
CN
CN
CN
Ph
Ph
H
CN
CN
H
NH
N
N
NH
N
N
Ph
Br
Ph
Ph
Ph
HN
HN
Nucleophilic
Addition
Ph
NO2
Br
Br
Ph
Ph
5
6
NH
N
N
Ph
Ph
NO2
H
CN
CN
Ph
Ph
Br
Ph
Br
HN
H
NH
N
N
N
N
N
N
Cu
Ph
Br
Ph
Ph
Br
Ph
HN
Electrophilic
Substitution
Br
Br
Br
Ph
Ph
Fig. 1 Regioselective reactivity in 2-nitroTPP
7
8
Chem. Commun., 1998
759

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(a)
(b)
chlorins, providing the first route to dodecasubstituted dihydro-
porphyrins. Dropwise addition of bromine (10 equiv.) in CHCl3
to 9 and 10 (100 mg scale) produced 11 and 12 in 88 and 84%
yields, respectively. Hexabromination of 11 resulted in a 26 nm
red shift of the Soret band (lmax 414 to 440 nm) and a 56 nm
1
shift for the Q band (lmax 604 to 660 nm). The H NMR
spectrum of 11 displayed two doublets at d 3.52 and 4.83,
characteristic of the trans chlorin functionality, and no peaks in
the aromatic b proton region. The molecular structure of
compound 11 was further confirmed by X-ray crystallography
(Fig. 2).‡ The macrocycle exhibits a ruffled-type conformation
with a mean deviation of 0.536 Å for the 24 core atoms from
their least-squares plane, and is significantly more nonplanar
than dibromochlorin 6 [Fig. 2(a)].
N(6)
N(8)
N(5)
N(6)
Br(1)
Br(2)
N(5)
N(7)
N(1)
N(7)
N(2)
N(3)
N(1)
N(4)
N(2)
Ni(1)
N(4)
N(3)
Br(6)
This work was supported by grants from the National Science
Foundation (CHE-96-23117) and the National Institutes of
Health (HL-22252).
Br(1)
Br(3)
Br(5)
Br(2)
Br(4)
Notes and References
Fig. 2 Molecular structure of (a) 6 (below: from top; above: edge-on view)
and (b) 11 (below: from top; above: edge-on view). Hydrogen atoms have
been omitted for clarity.
† E-mail: kmsmith@ucdavis.edu
‡ Crystal data for 6: C50H30Br2N8·(CHCl3·0.25MeOH), MW = 1030.0,
monoclinic, a
=
33.329(5), b
=
= 10.193(3), c = 27.787(4) Å, b
=
103.28(3)°, V
9187(3) Å3 (by least-square refinement on dif-
fractometer angles for 40 centered reflections), l = 1.54178 Å, space group
C2/c, Z = 8, Dc = 1.489 g cm23, F(000) = 4148. The single, purple
parallelipiped crystal with cell dimensions 0.36 3 0.04 3 0.02, m = 4.215
mm21, was collected on a Siemens P4 rotating anode diffractometer, scan
type 2q–q, T = 130(2) K, 2qmax = 112°, 10227 data, 6074 unique
[R(int) = 0.079], 4030 > 2s(I). The number of parameters was 529. Final
R factors were wR (all data) = 0.2206 and R (obs. data) = 0.085; the
A second route leading to dibromochlorin compounds
involves initial formation of the chlorin chromophore.11 In this
case, the reduced pyrrole functionality induces a favored
delocalization pathway, via thermodynamically more stable
N(22)H–N(24)H tautomerism, allowing regiospecific bromi-
nation to take place. Treatment of 5 (200 mg scale) with 2.5
equiv. of NBS in CHCl3 at 65 °C afforded 7 quantitatively.
Dropwise addition of bromine (2.5 equiv. in CHCl3) to 4
afforded the desired brominated product 6 in 91% yield. A
characteristic 10 nm red shift of the Soret band was observed
(lmax 408 to 418 nm) as a result of this reaction. As expected,
reaction of a Ni–chlorin 7 with 2.5 equiv. of bromine led to a
mixture of brominated products.12
maximum residual electron density was 0.883 e Å23
For 11: C50H24Br6N8Ni.2(CHCl3), MW
.
=
1513.68, triclinic,
a
= 12.911(3), b = 13.085(3), c = 18.383(4) Å, a = 75.47(3)°,
b = 71.60(3)°, g = 65.27(3)°, V = 2651.03(1) Å3 (by least-squares
refinement on diffractometer angles for 29 centered reflections),
¯
l
=
0.71073 Å, space group P1, Z
= 2, Dc = ,
1.896 g cm23
F(000) 1468. The single, purple parallelipiped crystal with cell
=
dimensions 0.50 3 0.30 3 0.20, m = 5.236 mm21, was collected on a
Siemens R3m/V diffractometer, scan type w, T = 130(2) K, 2qmax = 55°,
12887 data, 12269 unique [R(int) = 0.039], 9104 > 2s(I). The number of
parameters was 658. Final R factors were wR (all data) = 0.1939 and R (obs.
Reaction of the metal-free nitroporphyrin 1 with excess NBS
(or chlorin 4, with excess bromine, 10 equiv.) afforded only
dibrominated products 3 (or 6). In contrast, subjecting metal-
lated 2-nitroTPP and metallated dihydroporphyrins to excessive
bromination conditions produced the desired hexabrominated
products. When Cu-nitroTPP 2 was allowed to react with 16
equiv. of NBS in refluxing 1,2-dichloroethane, hexabromo-
2-nitroTPP 8 was produced in 70% yield.
data) = 0.067; the maximum residual electron density was 1.358 e Å23
.
Both structures 6 and 11 were solved by direct methods and refined (based
on F2 using all independent data) by full-matrix least-squares methods
(Siemens SHELXTL ver. 5.03). Hydrogen atom positions were located by
their idealized geometry and refined using a riding model. An absorption
correction was applied using XABS2 (ref. 13). CCDC 182/769.
Initial preparation of NiII–chlorins 9 and 10,11 followed by
excessive bromination, afforded the desired hexabromo-
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82, 105.
NC
NC
CN
CN
CN
CN
CN
CN
Br
Ph
Ni
Ph
Ni
3 J. A. Shelnutt, X. Song, W. Jentzen and C. J. Medforth, Chem. Soc. Rev.,
1998, in the press.
Br
Ph
Br
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59, 4433.
N
N
N
N
N
N
Ph
Br
Ph
Ph
N
N
Br
Br
Br
Ph
Ph
11
9
CO2Me
CO2Me
CO2Me
CO2Me
Ph
Ph
Ni
Br
Ph
Br
N
N
N
N
N
N
N
N
11 K. M. Shea, L. Jaquinod and K. M. Smith, submitted for publication;
L. Jaquinod, C. Gros, R. G. Khoury and K. M. Smith, Chem Commun.,
1996, 2581.
12 M. J. Crossley, P. L. Burn, S. S. Chew, F. B. Cuttance and I. A. Newsom,
J. Chem. Soc., Chem. Commun., 1991, 1564.
Ph
Ph
Ph
Br
Ni
13 S. R. Parkin, B. Moezzi and H. Hope, J. Appl. Cryst., 1995, 28, 53.
Br
Br
Ph
Ph
12
10
Received in Corvallis, OR, USA, 4th December 1997; 7/08766G
760
Chem. Commun., 1998