J. Am. Chem. Soc. 1996, 118, 1567-1568
1567
11
in CH2Cl2 in the presence of BF3‚OEt2 at room temperature
led to a reproducible yield of 10.5% of 5,10,15,20-tetrakis(2′,6′-
dinitro-4′-tert-butylphenyl)porphyrin, H2TDNPP (4).12 In order
to scale up this reaction, we undertook the same condensation
with 12 g of aldehyde 3, pyrrole (3.3 mL), and BF3‚OEt2 (6
mL) in CH2Cl2 (480 mL), which gave, after column chroma-
tography and precipitation, porphyrin 4 (1.28 g, 9% yield). The
octanitro porphyrin H2TDNPP (4) was dissolved in CH2Cl2
saturated with concentrated HCl and reduced with excess
SnCl2‚2H2O at -4 °C for 8 days,6c,d,13 affording 65% of 5,10,
15,20-tetrakis(2′,6′-diamino-4′-tert-butylphenyl)porphyrin, H2-
TDAPP (8). An 88% yield is obtained if the reaction is carried
out for 3 weeks at -18 °C.14 We have been able to make octa-
substituted derivatives of 4. For example, treating 8 with excess
(R)-Mosher’s acid chloride15 resulted in the formation of the
highly soluble 5,10,15,20-tetrakis(4′-tert-butyl-2′,6′-bis((R)-R-
(trifluoromethyl)-R-methoxyphenylacetamido)phenyl)por-
phyrin (10) (45% yield). Similarly, H2TAPP (8) and (R)-R-
methoxyphenylacetyl chloride gave the soluble 5,10,15,20-
tetrakis(4′-tert-butyl-2′,6′-bis((R)-R-methoxyphenylacet-
amido)phenyl)porphyrin (11) in 45% yield.
Synthesis of Biomimetic Heme Precursors: The
“Double Picket Fence” 5,10,15,20-Tetrakis(2′,6′-
dinitro-4′-tert-butylphenyl)porphyrin
Eric Rose,* Alain Kossanyi, Me´lanie Quelquejeu,
Miche`le Soleilhavoup, Fre´de´ric Duwavran,
Nicolas Bernard, and Alexandra Lecas
Laboratoire de Synthe`se Organique et Organome´tallique
URA CNRS 408, Tour 44, 4 Place Jussieu
75230 Paris Cedex 05, France
ReceiVed August 1, 1995
The various atropisomers of tetrakis(o-aminophenyl)porphyrin
have served as synthons for the creation of many biomimetic
hemes for the preparation of kinetically stable Fe dioxygen
complexes1 and for the creation of shape-selective and chiral
porphyrin oxygenation catalysts.2a These otherwise useful
synthetic approaches have two principal limitations: the separa-
tion of the desired atropisomers2b and the problem of creating
chiral faces simultaneously on both sides of the porphyrin. An
obvious solution to these problems could be attained through
the symmetric octakis(o-aminophenyl)porphyrin. In fact, two
papers describe the synthesis of this substance.3 All attempts
to reproduce this synthesis have failed; mute testimony to these
failures is the fact that no functionalized derivatives of this
octaamino porphyrin have ever been applied to biomimetic
reactions. Herein we describe an efficient synthesis of a similar
octaamino porphyrin bearing a tert-butyl group in the para
position of each meso-phenyl substituent; we also report “double
picket fence” type derivatives of this new porphyrin which augur
well for the creation of a new family of functional heme
analogues.
We were pleasantly surprised to find that a single pocket
could be introduced in high yield and selectively by reaction
(11) Lindsey, J. S.; Wagner, R. W. J. Org. Chem. 1989, 54, 828.
(12) Byproducts have been isolated and fully characterized which
correspond to (4-tert-butyl-2,6-dinitrophenyl)dipyrrylmethane (5) (5-10%
yield) and the corrole derivative (6) (UV/vis: 416, 580, 617 nm). Similarly,
condensation of 3,5-dinitro-4-methylbenzaldehyde and pyrrole in AcOH
led to a 2.5% yield of 5,10,15,20-tetrakis(3′,5′-dinitro-4′-methylphenyl)-
porphyrin, H2TNMPP (7a). Condensation of 2,6-dinitro-4-((isopropyloxy)-
carbonyl)benzaldehyde and pyrrole in CH2Cl2 in the presence of BF3‚OEt2
gives a 5% yield of 5,10,15,20-tetrakis(2′,6′-dinitro-4′-((isopropyloxy)-
carbonyl)phenyl)porphyrin, H2TDNIOCPP (7b).
Condensation of pyrrole and 2,6-dinitro- or 2,6-diaminoben-
zaldehyde did not succeed in our hands.3 We thought that a
solubility problem could explain this failure, so we decided to
use substituted alkyl, alkoxy, or alkoxycarbonyl 2,6-dinitroben-
zaldehydes. For example, we prepared 4-tert-butyl-2,6-dini-
trotoluene (1) (Chart 1) by nitration of 4-tert-butyltoluene (75%
yield).9 Bromination with NBS yielded 1-(bromomethyl)-2,6-
dinitro-4-tert-butylbenzene (2) in 90% yield. Oxidation of 2
10
by (Py)4Co(HCrO4)2 gave aldehyde 3 in 60% yield. Con-
densation of 2,6-dinitro-4-tert-butylbenzaldehyde (3) and pyrrole
(1) Momenteau, M.; Reed, C. A. Chem. ReV. 1994, 94, 659.
(2) (a) Collman, J. P.; Zhang, X.; Lee, V. G.; Uffelman, E. S.; Brauman,
J. I. Science 1993, 261, 1404. (b) Collman, J. P.; Gagne, R. R.; Reed, C.
A.; Halbert, T. R.; Lang, G.; Robinson, W. T. J. Am. Chem. Soc. 1975, 97,
1427.
(3) In the literature, two groups described at approximatively the same
time the condensation of 2,6-dinitrobenzaldehyde and pyrrole (0.75% yield
with CF3CO2H as catalyst4 and 2-13% yield with BF3‚OEt2 as catalyst).5
We and others6 were unfortunately not able to reproduce the preparation
of these interesting 5,10,15,20-tetrakis(2′,6′-dinitro- and -diaminophenyl)-
porphyrins.6
(4) Drain, C. M.; Corden, B. B. Inorg. Chem. 1989, 28, 4374.
(5) Quintana, C. A.; Assink, R. A.; Shelnutt, J. A. Inorg. Chem. 1989,
28, 3421.
(13) Lecas, A.; Boitrel, B.; Rose, E. Bull. Soc. Chim. Fr. 1991, 128,
407.
(14) (a) If reduction was undertaken at room temperature, overreduction
readily occurred, giving dihydroporphyrin 9 as a minor product with an
intense band at 656 nm characteristic of a chlorin band14b and adjacent
tetrahydroporphyrin: 5,10,15,20-tetrakis(2′,6′-diamino-4′-tert-butylphenyl)-
2,3,7,8-tetrahydroporphyrin with a double Soret band at 389 and 408 nm
and a characteristic Q band at 599 nm.
(6) (a) Collman, J. P.; Gagne, R. R.; Reed, C. A.; Halbert, T. R.; Lang,
G.; Robinson, W. T. J. Am. Chem. Soc. 1975, 97, 1427. (b) Momenteau,
M.; Mispelter, J.; Loock, B.; Lhoste, J. M. J. Chem. Soc., Perkin Trans. 1
1985, 221. (c) Rose, E.; Quelquejeu, M.; Pochet, C.; Kossanyi, A.; Julien,
N.; Hamon, L. J. Org. Chem. 1993, 58, 5030. (d) Rose, E.; Cardon-Pilotaz,
A.; Quelquejeu, M.; Bernard, N.; Kossanyi, A.; Desmazie`res, B. J. Org.
Chem. 1995, 60, 3919. (e) Rose, E.; Boitrel, B.; Quelquejeu, M.; Kossanyi,
A. Tetrahedron Lett. 1993, 34, 7267.
(7) Condensation of 2,6-diacetamidobenzaldehyde8a and pyrrole did not
give tetrakis(aryl)porphyrins. We reported previously that condensation
of 2,6-diacetamidobenzaldehyde and dipyrrylmethane did not afford the
5,15-bis(aryl)porphyrin.8b
(8) (a) Lecas, A.; Levisalles, J.; Mariacher, C.; Renko, Z.; Rose, E. Can.
J. Chem. 1984, 62, 2054. (b) Lecas, A.; Boitrel, B.; Rose, E. Tetrahedron
Lett. 1992, 33, 481.
(b) The Porphyrins, Structure and Synthesis; Dolphin, D., Ed.; Academic
Press, Inc.: New York, 1978; Part B, Vol. II, p 63.
(15) Le Maux, P.; Bahri, H.; Simonneaux, G. J. Chem. Soc., Chem.
Commun. 1991, 1350.
(9) (a) Verley, A. Bull. Soc. Chim. Fr. 1898, 19, 67. (b) Battegay, M.;
Heffely, P. Bull. Soc. Chim. Fr. 1924, 35, 981.
(10) Hu, Y.; Hu, H. Synth. Commun. 1992, 22, 1491.
0002-7863/96/1518-1567$12.00/0 © 1996 American Chemical Society