Novel synthesis and new chemistry of naphthochlorins

Article abstract of DOI:10.1039/a708765i

Reactions of 2-nitro-5,10,15,20-tetraphenylporphyrin with alkyl α-isocyanoacetates afford naphthochlorins (in addition to the expected pyrroloporphyrins) which undergo free radical dimerization; the X-ray structure of one such naphthochlorin dimer is repo

Full text of DOI:10.1039/a708765i

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Novel synthesis and new chemistry of naphthochlorins
Be´ne´dicte Krattinger, Daniel J. Nurco and Kevin M. Smith*†
Department of Chemistry, University of California, Davis, CA 95616, USA
Reactions of 2-nitro-5,10,15,20-tetraphenylporphyrin with
alkyl a-isocyanoacetates afford naphthochlorins (in addi-
tion to the expected pyrroloporphyrins) which undergo free
radical dimerization; the X-ray structure of one such
naphthochlorin dimer is reported.
able to reproduce the dimerization via the following methods. A
solution of naphthochlorin 5 in 1:1 CH2Cl2–MeOH (MeOH
optional) was stirred while exposed to the air. After 5 days the
presence of 5 was no longer detectable and naphthochlorin
dimer 14 was isolated in 37% yield. Alternatively, refluxing 5 in
dry benzene under argon with benzoyl peroxide (0.5 equiv.)
afforded 14 in 53% yield. The reaction presumably proceeds by
way of a p-stabilized radical on the non-aromatic b-carbon,
followed by a radical dimerization. There is ample precedent for
this type of reaction in the porphyrin literature; p-stabilized
radicals have been obtained from oxophlorins8 and some of
them dimerize9 by a mechanism similar to those involved in
phenolic chemistry.10
Tetrapyrrole macrocycles bearing fused aromatic rings have
attracted considerable attention, with examples including
benzoporphyrins,1 benzochlorins,2 pyrroloporphyrins,3a,b naph-
thoporphyrins,4 naphthochlorins5 and others.6 Many of these
possess long wavelength absorptions and are therefore potential
candidates as second generation photodynamic therapy photo-
sensitizers.7 The approaches to naphthochlorins described to
date have involved acid-catalyzed intramolecular cyclizations.
Thus, naphthochlorins were prepared from NiII and CuII
2-formyl-TPPs5b–d and from NiII 2-vinyl-TPPs.5a Herein we
report a novel base-promoted reaction which affords naphtho-
chlorins; we also show that naphthochlorins possess novel free-
radical chemistry wherein, in the presence of oxygen, a unique
covalently linked naphthochlorin dimer is obtained. This
naphthochlorin dimer represents the first example of a b–bA
linked bis(chlorin).
Nitroalkenes have been shown to react with a-isocyanoacet-
ates to give pyrroles.3c Treatment of nitroporphyrin 1 with
methyl or ethyl a-isocyanoacetate has been shown to afford
pyrroloporphyrins 2 and 3.3a,b Under similar reaction conditions
we have now discovered that reaction of 1 with tert-butyl
a-isocyanoacetate affords the expected pyrroloporphyrin 4‡ in
32% yield and an additional porphyrinic product, the naph-
thochlorin 5,‡ in 19% yield. Since our reaction conditions
involved basic rather than acidic conditions it is necessary to
postulate a new mechanistic route for naphthochlorin formation
(Scheme 1). We propose that addition of the tert-butyl a-
isocyanoacetate anion to nitroporphyrin 1 gives nitrochlorin 6
which eliminates HNO2 to afford porphyrin 7. Further reaction
of DBU with porphyrin 7 yields chlorin 8 which subsequently
undergoes two electrocyclic rearrangements (Scheme 1) to
afford naphthochlorin 5. Test reactions confirmed that naphtho-
chlorin 5 did not arise from pyrroloporphyrin 4. Further reaction
of nitroporphyrin 1 [refluxing 10:1 THF–EtOH, DBU (4
equiv.)] with ethyl a-isocyanoacetate (2 equiv.) yielded a
mixture of naphthochlorin 10 and pyrroloporphyrin 3; when
EtOH was replaced with BnOH a mixture of naphthochlorin 11
and pyrroloporphyrin 12 was obtained. A test reaction to
prepare naphthochlorin free of pyrroloporphyrin was under-
taken; isopropyl cyanoacetate (2 equiv.) was used instead of an
alkyl a-isocyanoacetate [refluxing 10:1 THF–PriOH, ni-
troporphyrin 1, DBU (4 equiv.)] and formation of naphtho-
chlorin 13 was observed. Although we were able to isolate
The identity of naphthochlorin dimer 14‡ was confirmed by
a crystal structure, as shown in Fig. 1. This structure is unique
among porphyrinoid crystal structures in that the dimeric
linkage features a direct Cb–CbA bond. The macrocycles are both
Ph
Ni
NO2
2
20
N
N
N
15
Ph
Ph
5
N
10
Ph
1
Ph
Ni
Ph
H
H
NH
CO2R
CO2R
N
N
N
N
N
N
Ni
Ph
Ph
Ph
N
N
Ph
Ph
2
3
4
R = Me
R = Et
5
R = But
10 R = Et
11 R = Bn
13 R = Pri
R = But
12 R = Bn
Ph
N
N
N
Ni
Ph
naphthochlorins 10, 11 and 13, yields for each were < 1% [lmax
/
N
Ph
Ph
nm (rel. int.) (CH2Cl2); 10: 440 (1), 604 (0.08), 662 (0.15); 11:
444 (1), 606 (0.08), 662 (0.18); 13: 440 (1), 604 (0.08), 668
(0.16); these optical data agree well with those of naphtho-
chlorin 5 (the structure of which has been confirmed by the
crystal structure of naphthochlorin dimer 14) and with those of
previously reported naphthochlorins5]. Full characterization of
naphthochlorins 10, 11 and 13 was not possible owing to the
scarcity and instability of these compounds.
N
ButO2C
H
Ph
Ni
N
N
N
Ph
H
CO2But
Attempted crystallization of naphthochlorin 5 from CDCl3–
MeOH afforded crystals of naphthochlorin dimer 14.‡ We were
14
Chem. Commun., 1998
757

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For 5: lmax(CH2Cl2)/nm 444 (e 153000), 614 (11000), 662 (29000);
dH(CDCl3) 5.19 (s, 2 H, reduced pyrrole ring H); m/z (LSIMS) 782.3 (M+
100). C,H,N combustion analysis satisfactory. Cyclic voltammetric meas-
urements were carried out with a Cypress Systems CS-1087 computer
controlled potentiostat. Naphthochlorin 5 undergoes two one electron
oxidations at E1/2 = 21.14 and 0.74 V; a single compartment cell was used
with a platinum disk working electrode, Ag/AgCl reference electrode, and
silver wire auxiliary electrode. Measurements (scan rate 110 mV s21) were
made in CH2Cl2, with Bu4NPF6 as supporting electrolyte. Ferrocene was
added as an internal reference.
CN
CO2R
NO2
NO2
_
NC
CHCO2R
N
N
DBU
1
6
For 14: lmax(CH2Cl2)/nm 440 (e 109000), 668 (16500), 712 (6800).
Crystals of meso-14 (C100H70N8O4Ni2·3.4CHCl3·0.5MeOH) were grown
by the slow diffusion of MeOH into a CHCl3 solution of 5. The selected
H
H
H
NC
C(NC)(CO2R)
CHCO2R
¯
crystal (0.20 3 0.25 3 0.50 mm) had a triclinic unit cell, space group P1 and
N
N
cell dimensions a
= 14.925(3), b = 17.025(3), c = 18.395(3) Å,
a = 90.896(12), b = 99.902(13), g = 105.083(13)°, V = 4436.9(12) Å3
and Z 2 (FW 1987.0). Data were collected on a Siemens P4
=
=
diffractometer with a rotating anode [l(Cu-Ka) = 1.54178 Å] at 130(2) K
in q/2q scan mode to 2qmax = 112°. Of 12130 reflections measured
(+h,±k,±l) 11578 were independent (Rint = 0.090) and 8509 had I > 2s
(Tmin = 0.50, Tmax = 0.56, rcalc = 1.487 g cm23, m = 3.85 mm21). The
structure was solved by direct methods and refined (based on F2 using all
independent data except for two suppressed reflections) by full-matrix least-
squares methods with 1038 parameters (Siemens SHELXTL V. 5.03).
Hydrogen atom positions were generated by their idealized geometry and
refined using a riding model. An empirical absorption correction was
applied (ref. 13). All of the solvate molecules were disordered; further
description of the solvate disorder and how it was treated is given in the
supplementary material. Final R factors were R1 = 0.092 (observed data)
and wR2 = 0.25 (all data). CCDC 182/768.
8
7
H
H
H
H
CO2R
H
CO2R
CN
N
N
9
5
Scheme 1
1 P. S. Clezy and C. W. F. Leung, Aust. J. Chem., 1993, 46, 1705;
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2 R. T. Holmes, J. J. Lin, R. G. Khoury, C. P. Jones and K. M. Smith,
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3 (a) L. Jaquinod, C. Gros, M. M. Olmstead, M. Antolovich and
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R. G. Khoury, M. M. Olmstead and K. M. Smith, J. Porphyrins
Phthalocyanines, 1997, 1, 201; (c) D. H. R. Barton, J. Kervagoret and
S. Z. Zard, Tetrahedron, 1990, 46, 7587;
4
T. D. Lash and C. P. Denny, Tetrahedron, 1995, 51, 59.
Fig. 1 Molecular structure of naphthochlorin dimer 14;‡ esters, non-fused
phenyl rings and hydrogen atoms (with the exception of those associated
with the direct dimer link) have been omitted for clarity
5 (a) M. A. Faustino, M. G. P. M. S. Neves, M. G. H. Vicente,
A. M. S. Silva and J. A. S. Cavaleiro, Tetrahedron Lett., 1995, 36, 5977;
(b) Y. V. Ishkov and Z. I. Zhilina, Zh. Org. Khim., 1995, 31, 136; (c)
L. Barloy, D. Dolphin, D. Dupre and T. P. Wijesekera, J. Org. Chem.,
1994, 59, 7976; (d) H. J. Callot, E. Schaeffer, R. Cromer and F. Metz,
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Acta, 1980, 45, L161.
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1, 1993, 2369; D. Dolphin, Can. J. Chem., 1994, 72, 1005.
8 R. G. Khoury, L. Jaquinod, A. M. Shachter, N. Y. Nelson and
K. M. Smith, Chem. Commun., 1997, 215; J.-H. Fuhrhop, S. Besecke
and J. Subramanian, J. Chem. Soc., Chem. Commun., 1973, 1;
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significantly ruffled11 with 0.33 and 0.36 Å mean deviations of
the macrocyclic atoms from their least-squares planes (calcu-
lated based upon the 24 core carbon and nitrogen atoms); the
average Ni–N bond length was 1.914(6) Å. The two macro-
cycles were nearly coplanar and exhibited an interplanar angle
of 30.1°, a mean plane separation of 3.70(14) Å, and a metal to
metal distance of 5.68 Å. Macrocyclic overlap was limited to
one pyrrolic subunit of each naphthochlorin monomer. A lateral
shift of 4.54 Å and a slip angle of 53(13)° were observed; in this
regard this structure bears a marked similarity to the bacterial
PRC ‘special pair’ which exhibits an overall geometry which is
generally similar and a lateral shift of ca. 6.6 Å.12
9 R. G. Khoury, L. Jaquinod, D. J. Nurco, R. K. Pandey and K. M. Smith,
Angew. Chem., Int. Ed. Engl., 1996, 35, 2496.
10 M. L. Mihailovic and C. Cekovic, in The Chemistry of the Hydroxyl
Group, Part 1, ed. S. Patai, Wiley, New York, 1971, pp. 505–592.
11 D. J. Nurco, C. J. Medforth, T. P. Forsyth, M. M. Olmstead and
K. M. Smith, J. Am. Chem. Soc., 1996, 118, 10918.
This work was supported by grants from the National Science
Foundation (CHE-96-23117) and the National Institutes of
Health (HL-22252). We thank Dr Timothy P. Forsyth for
carrying out the cyclic voltammetry experiments.
12 T. E. Clement, D. J. Nurco and K. M. Smith, Inorg. Chem., in the
press.
Notes and References
13 S. R. Parkin, B. Moezzi and H. Hope, J. Appl.Crystallogr., 1995, 28,
53.
† E-mail: kmsmith@ucdavis.edu
‡ Selected data for 4: lmax(CH2Cl2)/nm 444 (e 182000), 538 (9400), 558
(9800), 606 (14200); m/z (LSIMS) 809.3 (M+ 100%). C,H,N combustion
analysis satisfactory.
Received in Corvallis, OR, USA, 4th December 1997; 7/08765I
758
Chem. Commun., 1998