5,10-Diphenyltripyrrane, a useful building block for the synthesis of meso-phenyl substituted expanded macrocycles

Article abstract of DOI:10.1039/a704510g

Pyrrole and benzaldehyde were condensed under acidic conditions to produce a mixture of 5-phenyldipyrromethane and 5,10-diphenyltripyrrane; the tripyrrane was utilized in syntheses of meso-phenylsapphyrins, meso-diphenylpentaphyrin and meso-hexapnenylhexa

Full text of DOI:10.1039/a704510g

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5,10-Diphenyltripyrrane, a useful building block for the synthesis of
meso-phenyl substituted expanded macrocycles
Christian Bru¨ckner, Ethan D. Sternberg, Ross W. Boyle and David Dolphin*
Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, V6T 1Z1, Canada
Pyrrole and benzaldehyde were condensed under acidic
conditions to produce a mixture of 5-phenyldipyrromethane
and 5,10-diphenyltripyrrane; the tripyrrane was utilized in
syntheses of meso-phenylsapphyrins, meso-diphenylpenta-
phyrin and meso-hexaphenylhexaphyrin.
of heteroporphyrins.11 Tripyrrane 4 was obtained by us in yields
ranging typically from 10–20%, and, even when ground into a
powder, is stable in the solid form but could not, in our hands,
Ph
Ph
Expanded porphyrins1 are a diverse class of pyrrolic com-
pounds containing a larger macrocycle than that found in
porphyrins. They are being utilized in fields such as photody-
namic therapy (PDT),2 neutral substrate binding, anion recogni-
tion3 and annulene research.4 Although b-unsubstituted meso-
aryl substituted porphyrins are very prominent in the synthetic
porphyrin field,5 they are rarely found in expanded porphyr-
ins.6–8 This, perhaps, reflects the lack of a suitable building
block as well as the reduced stability of some of these systems,
as will be outlined below.
We report here the improved preparation of 5-phenyldi-
pyrromethane, itself an important building block for meso-
phenylporphyrinoids,8 the one-step synthesis of the novel
building block 5,10-diphenyltripyrrane and its use in 3 + 2- and
3 + 3-type syntheses to yield three meso-phenyl substituted
N
H
N
N
H
N
H
N
R1
R1
R2
R2
R3
R3
5 R1 = H, R2 = Et, R3 = Me
6 R1 = Ph, R2 = R3 = H
7 R1 = R2 = R3 = H
i
sapphyrins varying in their b-substituents,
a partially
4
+
5
b-substituted pentaphyrin and a fully b-unsubstituted meso-
N
H
N
H
OHC
CHO
hexaphenylhexaphyrin.
5-Phenyldipyrromethane 1 was synthesized by condensing
excess pyrrole 2 and benzaldehyde 3 in the presence of an acid
according to the procedures of Lee and Lindsey9 or Carrel,10
with the exception that generally 50% lower benzaldehyde to
pyrrole ratios were used and, most importantly, work-up
procedures were altered. The crude oils resulting from the
condensation were, after pre-purification by column chromat-
ography, transferred into a sublimation apparatus and heated
under high vacuum (Scheme 1). Under these conditions, 1
sublimed as a white crystalline material of analytical purity. The
reaction could be scaled up to provide up to 15 g (ca. 50% yield)
of 1 per run. The residue left in the bottom of the sublimation
apparatus hardened, upon cooling, into a red–orange glass.
Analysis of this glass proved that it contained ca. 95%
5,10-diphenyltripyrrane 4.† Lee and Lindsey9 and Vigmond
et al.11 have previously reported the occurrence of a small
ii
+ PhCHO
4
4
+
+
6
7
N
H
N
H
iii
N
H
N
H
OHC
CHO
4
+
NH HN
OHC
CHO
Ph
8
Ph
iv
N
H
NH
HN
1
amount of an unstable tailing component which, based on H
NMR spectroscopy, was provisionally assigned structure 4. In
subsequent work, Lee and co-workers synthesized this tri-
pyrrane in a multi-step procedure and utilized it in the formation
HN
NH
9
Scheme 2 Reagents and conditions: i, abs. EtOH (1 mm), O2 bubble, TsOH
(4 equiv.); evaporation of solvents in vacuo; column chromatography
(neutral alumina, activity I, 2.5% MeOH–CH2Cl2); ii, CH2Cl2, under N2,
BF3·Et2O (cat.), 1 h; chloranil, reflux, 30 min; evaporation of solvents in
vacuo; column chromatography (neutral alumina, activity I, 2.5% MeOH–
CH2Cl2); preparative TLC (alumina, 1:1 CH2Cl2–CCl4); iii, abs. EtOH (1
mm), O2 bubble, TsOH (4 equiv.); evaporation of solvents in vacuo;
trituration with CHCl3; preparative TLC (silica gel, 0.5% MeOH–CH2Cl2);
iv, CH2Cl2, TFA (cat.), 48 h, room temp., neutralisation with Et3N, then an
additional 36 h; column chromatography (neutral alumina, 1–3% MeOH–
Ch2Cl2); then preparative TLC (silica gel, CH2Cl2–20% EtOAc–1%
Et3N)
N
Ph
Ph
Ph
H
N
H
2
+
i–iv
+
NH
HN
NH
HN
OHC Ph
3
1
4
Scheme 1 Reagents and conditions: i, pyrrole, PhCHO (1 : 10) (neat), TFA
(5%), 1 h, under N2, or pyrrole, PhCHO (1:8), PhMe, reflux, TsOH (cat.),
under N2; ii, evaporation of solvents in vacuo; iii, flash chromatography
(silica gel, CH2Cl2); iv, sublimation at 130 °C at 1 torr, initial heating: 1 °C
min21
Chem. Commun., 1997
1689

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be further purified without retrieving it as an unstable oil. We
attribute this, in part, to the presence of three stereoisomers in 4.
This route to tripyrrane 4 is comparatively simple given that the
syntheses of b-alkyltripyrranes generally involve many reaction
steps from starting materials which are not commercially
available, unlike pyrrole and benzaldehyde. It is anticipated that
the ease of preparation of 4 will encourage its use as a synthetic
building block.
expanded macrocycles pentaphyrin and hexaphyrin exhibit a
significantly decreased stability when compared with their
b-alkyl analogues. This stability trend has been observed
before,8 and, if this is a general trend, may limit the extent to
which meso-phenyl substituted analogues of other known
expanded macrocycles can be made.
This work was supported by the Natural Sciences and
Engineering Council of Canada.
With the novel 5,10-diphenyltripyrrane 4 in hand, we had the
opportunity to prepare meso-diphenyl substituted sapphyrins 5
and 7‡ and, in a four-component Rothemund-type condensa-
tion, meso-tetraphenylsapphyrin 6 (Scheme 2). Recently, Sess-
ler et al. published the synthesis of 5 via a multi-component
condensation under Lindsey-type conditions6 and Chmielewski
et al. published the isolation of sapphyrin 6 as a side-product
from a Rothemund synthesis of tetraphenylporphyrin.7 Both
procedures, however, produce the particular sapphyrins in low
yields (ca. 10 and 1.1%, respectively) and both require
extensive chromatographic work-up. The syntheses presented
here using the preformed tripyrrolic precursor are short,
produce up to 39% yield in the final sapphyrin condensation (for
5) and, due to the absence of any other porphyrinic by-products,
require only minimal chromatographic work-up. The inversion
of one pyrrolic unit in 7 upon protonation–deprotonation as
observable by NMR spectroscopy is analogous to that described
before for 6.7 The meso-positions flanking the ‘flipping’
pyrrolic unit do not participate in this inversion.
A TFA catalysed 3 + 2-type condensation of tripyrrane 4 and
dipyrromethane 8 in the presence of nitrogen, followed by
treatment with base and then by chromatography, produced the
orange meso-diphenyltetra-b-alkyl pentaphyrin 9 in 13% yield
(Scheme 2). The pentaphyrin was characterized by 1H NMR
spectroscopy, mass spectrometry and UV-VIS spectroscopy.§
Its optical properties are similar to those of previously reported
b-alkyl pentaphyrins.13 The strongly solvent-dependent 1H
NMR spectrum can be rationalized in terms of inversions of
pyrrolic units similar to those observed in sapphyrins. However,
unlike the stable b-alkyl pentaphyrins, this macrocycle ex-
hibited poor stability even in the solid state and decomposed
when exposed to air, with a half-live of several days. It remains
to be seen whether the macrocycle can be stabilized by metal
complexation.14
Footnotes and References
* E-mail: david@dolphin.chem.ubc.ca
† Selected data for 4: 1H NMR (200 MHz, CD2Cl2): d 5.35 (s, 2 H), 5.78 (d,
J = 4, 2 H), 5.89 (s, 2 H), 6.14 (m, 2 H), 6.66 (m, 2 H), 7.15–7.38 (m, 10
H), 7.75 (br s, 1 H), 7.88 (br s, 2 H); HRMS (EI, 200 °C) C26H23N3 requires
377.1892. Found: 377.1881.
‡ Selected data for 7: 1H NMR (400 MHz, CDCl3): d 21.52 (s, 2 H), 20.1
(br s, 1 H), 7.15–7.20 (m, 1 H), 7.25–7.30 (m, 1 H), 7.60 (t, 3J 7, 2 H), 7.85
(t, 3J 8, 4 H), 8.49 (br s, 4 H), 9.24 (d, 3J 4.5, 2 H), 9.43 (d, 3J 4.5, 2 H), 9.60
(d, 3J 4.5, 2 H), 10.20 (d, 3J 5.0, 2 H), 10.27 (s, 2 H); lmax/nm (CH2Cl2–trace
Et3N) (log e) 478 (4.86), 506 (4.71), 626 (3.67), 686 (3.97), 708 (sh), 786
(3.62); HRMS (EI, 180 °C) C36H25N5 requires 527.21100. Found:
527.21015. For 7·2HCl: lmax/nm (CH2Cl2–trace HCl) (log e) 482 (5.47),
656 (4.13), 682 (4.13), 724 (sh), 758 (4.70) nm.
§ Selected data for 9: 1H NMR (400 MHz, CDCl3–TFA): d 23.6 (br s, 1 H),
2.9 (br s, 2 H), 2.12 (t, 3J 8.2, 6 H), 4.08 (s, 6 H), 4.56 (br q, 3J 8, 4 H), 7.5
(br m, 10 H), 8.1 (m, 4 H), 8.6 (br s, 2 H), 11.4 (s, obscured by TFA signal),
11.5 (s, obscured by TFA signal); lmax/nm (CH2Cl2–TFA) (log e) 492
(1.21), 682 (0.072), 742 (0.046); HRMS (LSIMS, thioglycerol) C43H40N5
requires 626.32837. Found: 626.32756.
¶ Selected data for 10: lmax/nm (CH2Cl2) (rel. intensity) 385 (0.95), 466
(0.46), 520 (0.5) 636 (1.0); HRMS (EI, 350 °C) C66H44N6 requires
920.36273. Found: 920.36550.
1 J. L. Sessler and S. J. Weghorn, Expanded, Contracted, and Isomeric
Porphyrins, Pergamon, N.Y., 1997; A. Jasat and D. Dolphin, Chem.
Rev., 1997, in the press.
2 D. Dolphin, Can. J. Chem., 1994, 72, 1005; R. Bonnett, Chem. Soc.
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5 J. B. Kim, A. D. Adler and F. R. Longo, in The Porphyrins, ed. D.
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Lindsey, S. Prathapan, T. E. Johnson and R. W. Wagner, Tetrahedron,
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On the other hand, a 3 + 3-type condensation reaction
employing 4 and benzaldehyde 3 furnished, after oxidation with
chloranil and chromatography, a blue product which could be
identified by its mass and UV-VIS spectra as the meso-
hexaphenylhexaphyrin 10.¶ Its 1H NMR was complex and
Ph
Ph
N
H
N
N
Ph
Ph
9 C.-H. Lee and J. S. Lindsey, Tetrahedron, 1994, 50, 11427.
10 T. Carell, Ph.D. Thesis, Ruprechts-Karl-Universita¨t, Germany, 1993.
See footnotes of: G. Shipps, Jr. and J. Rebek, Jr., Tetrahedron Lett.,
1994, 35, 6823.
11 S. J. Vigmond, M. C. Chang, K. M. R. Kallury and M. Thompson,
Tetrahedron Lett., 1994, 35, 2455.
N
HN
Ph
N
Ph
12 P.-Y. Heo, K. Shin and C.-H. Lee, Tetrahedron Lett., 1996, 37, 197;
P. Y. Heo and C.-H. Lee, Bull. Korean Chem. Soc., 1996, 17, 515.
13 H. Rexhausen, and A. Gossauer, J. Chem. Soc., Chem. Comm., 1983,
275; R. E. Dansodanquah, L. Y. Xie and D. Dolphin, Heterocycles,
1995, 41, 2553.
10
largely depended on pH and the nature of the solvent. This may
reflect its non-static conformation. Such flexibility of the
macrocycle has also been observed for b-alkyl hexaphyrins.
Further studies of this macrocycle were hampered by its
instability.
14 A. K. Burrell, G. Hemmi, V. Lynch, and J. L. Sessler, J. Am. Chem. Soc.,
1991, 113, 4690.
The above examples prove the synthetic utility of 4. It also
emerges that the meso-phenyl substituted versions of the larger
Received in Corvallis, OR, USA, 26th February 1997; revised manuscript
received, 26th June 1997; 7/04510G
1690
Chem. Commun., 1997