Synthesis of aromatic dicarbaporphyrinoids from resorcinol and 2-methylresorcinol

Article abstract of DOI:10.1016/j.tetlet.2006.10.053

23-Carba-oxybenziporphyrins, a new group of dicarbaporphyrinoids, are easily prepared by reacting tripyrrane analogues derived from resorcinol or 2-methylresorcinol with an indene dialdehyde under MacDonald '3+1' conditions.

Full text of DOI:10.1016/j.tetlet.2006.10.053

Tetrahedron Letters 47 (2006) 8863–8866
Synthesis of aromatic dicarbaporphyrinoids from
resorcinol and 2-methylresorcinolI
Linlin Xu and Timothy D. Lash*
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, United States
Received 16 September 2006; revised 10 October 2006; accepted 11 October 2006
Available online 30 October 2006
Abstract—23-Carba-oxybenziporphyrins, a new group of dicarbaporphyrinoids, are easily prepared by reacting tripyrrane
analogues derived from resorcinol or 2-methylresorcinol with an indene dialdehyde under MacDonald ‘3+1’ conditions.
Ó 2006 Elsevier Ltd. All rights reserved.
Carbaporphyrinoids, porphyrin analogues with carbo-
cyclic rings in place of one of the usual pyrrole subunits,
were first reported in the mid-1990s.1,2 Oxybenziporph-
yrin 1, the first aromatic example of this type, retains
strongly diatropic characteristics in its proton NMR
spectrum, showing the internal CH upfield near
ꢀ7 ppm, as well as a porphyrin-like UV–vis absorption
spectrum.3–5 Subsequently, many additional aromatic
carbaporphyrinoids were reported, including benzocar-
baporphyrins 2.6–9 These systems show varying degrees
of aromatic character and give unusual chemistry,
including the ability to generate stable organometallic
derivatives under mild conditions.10–13 In addition, ke-
tals derivatives generated by the oxidation of carbapor-
phyrins with ferric chloride14 have been shown to
be active agents in the treatment of leishmaniasis.15
However, little work has been conducted to date on
dicarbaporphyrinoid systems, where two of the
usual pyrrole rings are replaced by carbocyclic rings.16,17
A dibenzodicarbaporphyrin 3 was prepared from
1,3-diformylindane and 3,4-diethylpyrrole in a one-pot
procedure,16 but this methodology does not have
general application for the synthesis of related macrocy-
cles. An example of a 23-carbaazuliporphyrin 4 was also
obtained using a stepwise route via an azulene analogue
of the tripyrranes.17 In addition, two types of related
doubly N-confused porphyrin systems, 5 and 6, have
also been reported.18,19 Carbaporphyrins provide a link
between the porphyrins and the annulenes,1,2 but also
show useful characteristics such as the ability to form
complexes with higher oxidation levels for transition
metal elements.11–13 Oxybenziporphyrins easily afford
silver(III) derivatives,12 while benzocarbaporphyrins 2
form both silver(III) and gold(III) organometallic deriv-
atives.11 N-confused porphyrins,20 and doubly N-con-
fused porphyrins 5 and 6, also share this ability giving
silver(III) and copper(III) derivatives.18–20 Hence, the
development of syntheses for other families of
dicarbaporphyrinoids has a considerable significance in
this rapidly developing field.
Recently, we reported the synthesis of tripyrrane ana-
logues 7 from resorcinol and 2-methylresorcinol.21 The
reaction of 2 equiv of acetoxymethylpyrrole 8 with the
dihydroxybenzene in dichloromethane with p-toluene-
sulfonic acid and calcium chloride as cocatalysts gave
‘benzitripyrranes’ 7 in 30–33% yields (Scheme 1). Depro-
tection of the benzyl esters gave the related dicarboxylic
acids 9. These were reacted with indene dialdehyde 1022
in TFA–dichloromethane for 16 h. The solutions were
washed with 0.1% ferric chloride solution to aid in the
oxidation of the porphyrinoid products. Subsequent
washing with aqueous sodium bicarbonate, followed
by the evaporation of the solvents on a rotary evapora-
tor, gave residues that were virtually insoluble in dichlo-
romethane or chloroform and these poor solubility
characteristics prevented us from purifying the products
by column chromatography. The crude product derived
from resorcinol tripyrrane 7a was recrystallized from
methanol to give brown crystals in a 40% yield. Further
recrystallization from chloroform–methanol gave the
q Part 41 in the series ‘Conjugated Macrocycles Related to the
Porphyrins’. For Part 40, see: El-Beck, J. A.; Lash, T. D. Org. Lett.,
in press.
*
Corresponding author. Tel.: +1 309 438 8554; fax: +1 309 438
5538; e-mail: tdlash@ilstu.edu
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.10.053

8864
L. Xu, T. D. Lash / Tetrahedron Letters 47 (2006) 8863–8866
O
OH
N
Me
19
Et
Me
R
21
2
1
20
N
3
OH
18
R
Me
CO2R2
Et
R
Et
R
HO
4
N
H
N
22
17
5
H
p
-TSA
CaCl2
Me
25
HO
H
6
16
15
H
23
N
H
24
H
7
N
N
N
Et
Me
2
Me
Et
14
13
R
8
CO2R2
12
10
CH2
9
11
Et
R
AcO
Et
Me
1
N
2
H
7 R2 = Bn 9 R2 = H
Oxybenziporphyrin
Benzocarbaporphyrin
CO2Bn
8
a. R = H; b. R = Me
Me
Me
20
1. H+
2
1
CHOH
Et
Et
3
2. FeCl3
N
N
4
21
24
OHC
10
H
5
15
22
N
H
H
23
N
Me
Me
O
OH
Et
10
Et
Et
R
HO
R
Et
4
Me
3
Me
O
23-Carbaazuliporphyrin
opp-Dicarbaporphyrin
N
H
N
H
H
Ar
Ar
N
OEt
H
N
N
Et
Et
N
OR
Ar
N
N
Me
Me
H
11
11'
Ar
Ar
Ar
H
H
N
- H+
a. R = H b. R = Me
+ H+
N
N
H
N
H
O
OH
R
Et
Ar
Ar
Et
R
HO
5
6
Ar = C6F5
Me
H
Me
O
N
N
H
H
pure dicarbaporphyrinoid 11a in a 25% yield.23 The
product derived from methylresorcinol tripyrrane 7b
was similarly crystallized from methanol and then chlo-
roform methanol to give the related dicarbaporphyri-
noid 11b as a brown powder in an 18% yield.23
Porphyrins and their analogues usually dissolve to a
greater extent in chlorinated solvents such as CHCl3
than other organic solvents, and in cases where they
are sparingly soluble addition of TFA greatly improves
the solubility by generating the corresponding dications.
However, 11a and 11b were virtually insoluble in chloro-
form and the addition of TFA had no beneficial effect. It
should be noted, however, that this system does not
have the basic imine-type nitrogens found in porphyrins.
Fortunately, porphyrinoids 11a and 11b are sparingly
soluble in pyridine and to a slightly greater extent in
DMSO, and this allowed us to acquire proton NMR
data. DMSO is usually a poor solvent for porphyrinoid
systems, but the observed solubility of 11 is presumably
due to hydrogen bonding interactions to the resorcinol
subunit (Fig. 1). The proton NMR spectrum of 11b in
DMSO-d6 showed no plane of symmetry, indicating that
the interconversion between the 2 equiv hydroxy-
oxybenziporphyrinoid tautomers 11b and 11b0 is slow,
and four resonances were observed for the meso-bridge
protons at 9.56, 9.70, 9.98 and 10.02 ppm (Fig. 2A).
An additional resonance was observed for the OH at
10.42 ppm, confirming the hydrogen bonding interac-
tion depicted in Figure 1, while the 2-CH3 was present
at 2.44 ppm. The internal protons were all shifted up-
field, giving two singlets for the CHs at ꢀ5.11 and
ꢀ4.82 ppm, together with two NH resonances at
H
H
N
N
Et
Et
Me
Me
12
Scheme 1.
O
Et
R
3
21
2
19
1
20
18
Me
O
Me2S O
4
H
N
17
5
22
H
25
6
16
15
14
H
23
N
7
8
24
141
142
Et
12
13
131
10
9
11
Me
132
Figure 1. Structure of hydrogen bonded dicarbaporphyrinoids 11 in
DMSO showing the numbering system for the porphyrinoid
macrocycle.
ꢀ1.89 and ꢀ1.52 ppm. This highly diatropic character
confirms that the carbaporphyrinoid system is aromatic.
The addition of a drop of TFA to the NMR solution
gave a similar but somewhat simplified proton NMR
spectrum that showed a plane of symmetry and only
two 2H resonances for the meso-protons (Fig. 2B). This
indicates, as was expected, that the presence of acid in-
creases the rate at which tautomers 11b and 11b0 inter-
convert. However, the protonated species 12b may also

L. Xu, T. D. Lash / Tetrahedron Letters 47 (2006) 8863–8866
8865
sulted in a sharper Soret band that was blue shifted to
448 nm and a strong Q band was observed at 622 nm
(these differences are consistent with the formation of
a protonated species 12). The UV–vis data for in pyri-
dine were also similar, showing the Soret absorption at
455 nm and a Q band at 599 nm. Addition of 1%
DBU to solutions of 11a in methanol–chloroform also
showed distinctive changes in the UV–vis spectrum with
the Soret band shifting to 446 nm, suggesting the forma-
tion of the anionic species. Similar results were obtained
for 11b, although the spectra were generally of a lower
quality due to aggregation effects.
Figure 2. Partial 400 MHz proton NMR spectra of 24-carba-oxy-
benziporphyrin 11b showing the upfield and downfield regions. (A)
Spectrum in DMSO-d6 showing the absence of a plane of symmetry in
addition to the highly diatropic character of this porphyrinoid species.
(B) Spectrum in TFA–DMSO-d6 showing the apparent symmetrical
nature of the structure under these rapid exchange conditions. The tail
end of a broad peak centred on 6.8 ppm, that corresponds to the TFA,
can also be seen.
Dicarbaporphyrinoids 11a and 11b have very different
solubility characteristics from any porphyrin analogue
system that we have investigated previously. Although
we have not as yet been able to metalate these structures,
these unusual macrocyclic systems still show highly dia-
tropic proton NMR spectra and porphyrin-like UV–vis
spectra. This new group of dicarbaporphyrinoids dem-
onstrates that highly modified benziporphyrins can re-
tain aromatic character. However, it remains to be
seen if related tri or tetracarbaporphyrinoids systems
can be prepared or whether they will still retain porphy-
rin-like characteristics.
be present as well (Scheme 1). The proton NMR spec-
trum of 11b in pyridine-d5 also showed only two 2H
singlets for the meso-protons at 9.87 and 10.85 ppm,
while the internal CHs appeared at ꢀ4.24 and
ꢀ3.99 ppm and the NHs gave a 2H resonance at
ꢀ1.50 ppm. These data also suggests that the tautomers
interconvert more rapidly in the presence of a basic sol-
vent, although anionic species may also be present in
solution. A carbon-13 NMR spectrum of 11b was ob-
tained in TFA–DMSO-d6 and this showed the carbonyl
resonance at 175.3 ppm. Similar proton NMR data were
obtained for 11a, which also showed asymmetry in
DMSO-d6 but took on the appearance of a plane of
symmetry in TFA–DMSO-d6 or pyridine-d5.
Acknowledgments
This material is based upon work supported by the
Donors of the Petroleum Research Fund, administered
by the American Chemical Society and the National
Science Foundation under Grant Nos. CHE-0134472
and CHE-0616555.
The IR spectra for 11a and 11b showed carbonyl
stretching (mC@O) at 1594 cmꢀ1 and an OH absorption
at approximately 3430 cmꢀ1. This compares to the val-
ues of 1611 (mC@O) and 3440 cmꢀ1 (mOH) for a related
3-hydroxyoxybenziporphyrin.5 The UV–vis spectra of
11a and 11b were porphyrin-like, showing the presence
of strong Soret bands near 450 nm, although there were
significant variations depending upon the solvent used.
In addition, the quality and intensity of the spectra
varied due to aggregation in solution. For instance,
the UV–vis spectrum of 11a in chloroform gave a Soret
band at 458 nm but in 50% methanol–chloroform the
Soret band shifted to 451 nm and a clearer Q band
was noted at 602 nm (Fig. 3). The addition of TFA re-
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tetlet.
2006.10.053.
References and notes
1. Lash, T. D. Synlett 2000, 279.
2. Lash, T. D. In The Porphyrin Handbook; Kadish, K. M.,
Smith, K. M., Guilard, R., Eds.; Academic Press: San
Diego, 2000; Vol. 2, pp 125–199.
3. Lash, T. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 2533.
4. Lash, T. D.; Chaney, S. T.; Richter, D. T. J. Org. Chem.
1998, 63, 9076.
5. Richter, D. T.; Lash, T. D. Tetrahedron 2001, 57, 3659.
6. (a) Lash, T. D.; Hayes, M. J. Angew. Chem., Int. Ed. 1997,
36, 840; (b) Lash, T. D. Chem. Commun. 1998, 1683.
7. Lash, T. D.; Hayes, M. J.; Spence, J. D.; Muckey, M. A.;
Ferrence, G. M.; Szczepura, L. F. J. Org. Chem. 2002, 67,
4860.
8. Liu, D.; Lash, T. D. J. Org. Chem. 2003, 68, 1755.
9. For related carbachlorins, see: Hayes, M. J.; Lash, T. D.
Chem. Eur. J. 1998, 4, 508.
10. (a) Graham, S. R.; Ferrence, G. M.; Lash, T. D. Chem.
Commun. 2002, 894; (b) Lash, T. D.; Colby, D. A.;
Figure 3. Electronic absorption spectra of 11a in 50% methanol–
chloroform (red line) or 1% TFA in 50/50 methanol–chloroform (blue
line).

8866
L. Xu, T. D. Lash / Tetrahedron Letters 47 (2006) 8863–8866
Graham, S. R.; Ferrence, G. M.; Szczepura, L. F. Inorg.
Chem. 2003, 42, 7326.
11. (a) Muckey, M. A.; Szczepura, L. F.; Ferrence, G. M.;
Lash, T. D. Inorg. Chem. 2002, 41, 4840; (b) Lash, T. D.;
Colby, D. A.; Szczepura, L. F. Inorg. Chem. 2004, 43,
5258.
12. Lash, T. D.; Rasmussen, J. M.; Bergman, K. M.; Colby,
D. A. Org. Lett. 2004, 6, 549.
13. Bergman, K. M.; Ferrence, G. M.; Lash, T. D. J. Org.
Chem. 2004, 69, 7888.
14. (a) Hayes, M. J.; Spence, J. D.; Lash, T. D. Chem.
Commun. 1998, 2409; (b) Lash, T. D.; Muckey, M. A.;
Hayes, M. J.; Liu, D.; Spence, J. D.; Ferrence, G. M. J.
Org. Chem. 2003, 68, 8558.
15. Kamowski, E. M.; Passini, J.; Jones, M. A. ; Lash, T. D.
Book of Abstracts for the 227th National ACS Meeting,
Anaheim CA, 2004, MEDI 58.
16. Lash, T. D.; Romanic, J. L.; Hayes, M. J.; Spence, J. D.
Chem. Commun. 1999, 819.
17. Graham, S. R.; Colby, D. A.; Lash, T. D. Angew. Chem.,
Int. Ed. 2002, 41, 1371.
MeOH–CHCl3): kmax (log10 e) 368 (4.41), 451 (4.91), 557
(3.95), 602 (4.26), 713 nm (3.29); UV–vis (5% Et3N in 50/
50 MeOH–CHCl3): kmax (log10 e) 376 (4.53), 450 (4.90),
544 (4.00), 593 nm (4.13); UV–vis (1% TFA in 50/50
MeOH–CHCl3): kmax (log10 e) 368 (4.35), 465 (4.83), 531
(3.71), 574 (4.00), 622 nm (4.51); IR (KBr): m 3430 (mOH),
1594 cmꢀ1 (mC@O); 1H NMR (DMSO-d6): d ꢀ5.13 (1H, s),
ꢀ4.84 (1H, s), ꢀ1.92 (1H, s), ꢀ1.54 (1H, s), 1.58 (6H, m),
3.3 (6H, s, obscured by solvent), 3.78 (4H, m), 7.62 (2H,
m), 7.9 (1H, br), 8.77 (2H, m), 9.56 (1H, s), 9.70 (1H, s),
9.98 (1H, s), 10.02 (1H, s), 10.42 (1H, s); 1H NMR (TFA–
DMSO-d6): d ꢀ4.92 (1H, s), ꢀ4.64 (1H, s), ꢀ1.49 (2H, s),
1.57 (6H, t, J = 7.4 Hz), 3.31 (6H, s), 3.76 (4H, q,
J = 7.2 Hz), 7.62 (2H, m), 7.9 (1H, obscured by solvent),
8.75 (2H, m), 9.58 (2H, s), 9.96 (2H, s); 1H NMR
(pyridine-d5): d ꢀ4.26 (1H, s), ꢀ4.05 (1H, s), ꢀ1.65 (2H,
s), 1.55 (6H, t, J = 7.4 Hz), 3.22 (6H, s), 3.75 (4H, q,
J = 7.6 Hz), 7.82–7.85 (2H, m), 8.94–8.98 (2H, m), 9.90
(2H, s), 10.83 (2H, s); HRMS (FAB): Calcd for
C33H30N2O2: 486.2307. Found 486.2306.
8,19-Diethyl-4-hydroxy-3,9,18-trimethyl-24-carbabenzo[m]-
oxybenziporphyrin (11b). Using the foregoing procedure,
methylresorcinol tripyrrane analogue 9b (75.0 mg) was
reacted with indene dialdehyde 10 (28.4 mg). Following
evaporation of the solvent, the residue was recrystallized
from methanol and then chloroform–methanol to give 11b
(14.8 mg; 18%) as a brown powder, mp>300 °C; UV–vis
(DMSO): kmax (log10 e) 377 (4.56), 451 (4.77), 523 (4.32),
595 (4.28), 719 (3.75), 778 nm (3.48); UV–vis (10% TFA–
DMSO): kmax (log10 e) 453 (4.70), 468 (4.70), 521 (4.27),
579 (4.20), 626 nm (4.37); IR (KBr): m 3425 (mOH),
1595 cmꢀ1 (mC@O); 1H NMR (DMSO-d6): d ꢀ5.11 (1H,
s), ꢀ4.82 (1H, s), ꢀ1.89 (1H, s), ꢀ1.52 (1H, s), 1.60 (6H,
m), 2.44 (3H, s), 3.31 (6H, s), 3.80 (4H, m), 7.63 (2H, m),
8.77 (2H, m), 9.56 (1H, s), 9.70 (1H, s), 9.98 (1H, s), 10.02
(1H, s), 10.42 (1H, s); 1H NMR (TFA–DMSO-d6): d
ꢀ4.89 (1H, s), ꢀ4.61 (1H, s), ꢀ1.46 (2H, s), 1.57 (6H, t,
J = 7.4 Hz), 2.42 (3H, s), 3.31 (6H, s), 3.76 (4H, q,
J = 7.2 Hz), 7.62 (2H, m), 8.75 (2H, m), 9.57 (2H, s), 9.95
(2H, s); 1H NMR (pyridine-d5): d ꢀ4.24 (1H, s), ꢀ3.99
(1H, s), ꢀ1.50 (2H, s), 1.54 (6H, t, J = 7.4 Hz), 3.10 (3H,
s), 3.23 (6H, s), 3.75 (4H, q, J = 7.6 Hz), 9.87 (2H, s),
10.85 (2H, s) (benzo-protons obscured by solvent); 13C
NMR (TFA–DMSO-d6): d 10.7, 11.4, 17.4, 19.7, 98.2,
104.6, 112.3, 113.5, 115.0, 120.7, 121.5, 127.4, 130.8, 134.5,
136.3, 141.6, 142.2, 175.3; HRMS (FAB): Calcd for
C34H32N2O2: 500.2464. Found 500.2464.
18. (a) Araki, K.; Winnischofer, H.; Toma, H. E.; Maeda, H.;
Osuka, A.; Furuta, H. Inorg. Chem. 2001, 40, 2020; (b)
Ogawa, T.; Furuta, H.; Morino, A.; Takahashi, M.; Uno,
H. Organomet. Chem. 2000, 611, 551.
19. Maeda, H.; Osuka, A.; Furuta, H. J. Am. Chem. Soc.
2003, 125, 15690.
20. (a) Furuta, H.; Ogawa, T.; Uwatoko, Y.; Araki, K. Inorg.
Chem. 1999, 38, 2676; (b) Furuta, H.; Maeda, H.; Osuka,
A. Chem. Commun. 2002, 1795.
21. Miyake, K.; Lash, T. D. Chem. Commun. 2004, 178.
22. Arnold, Z. Collect. Czech. Chem. Commun. 1965, 30, 2783.
23. 8,19-Diethyl-4-hydroxy-9,18-dimethyl-24-carbabenzo[m]oxy-
benziporphyrin (11a). Resorcinol tripyrrane analogue 9a
(75.0 mg) was stirred under nitrogen with TFA (1 mL) in a
250 mL pear shaped flask for 2 min. Dichloromethane
(200 mL) was added, followed immediately by diformyl
indene 10 (29.3 mg), and the resulting mixture stirred in
the dark under nitrogen for 16 h. The mixture was shaken
with 0.1% w/v aqueous ferric chloride solution (200 mL)
for 5 min, and then washed with water, sodium bicarbon-
ate solution and water. The aqueous phases were back
extracted with chloroform at each stage. The solvent was
removed under reduced pressure and the resulting brown
residue recrystallized from methanol and then chloro-
form–methanol to give the dicarbaporphyrin (20.3 mg,
25%) as a dark purple powder, mp >300 °C; UV–vis (50%