Facile synthesis of meso-substituted dipyrromethanes and porphyrins using cation exchange resins

Article abstract of DOI:10.1016/S0040-4020(03)00245-X

The macroporosity and acidity of cation exchange resins play a crucial role in the synthesis of dipyrromethanes and porphyrins; for the first time, cation exchange resins have been used as heterogeneous solid acid catalysts to produce dipyrromethanes and porphyrins in good yields. The reaction, at room temperature, of substituted aromatic aldehydes with pyrrole catalysed by cation exchange resin afforded the corresponding meso-substituted dipyrromethane in yields ranging from 70 to 80%, indicating the broad scope of the reaction. Further, the condensation of meso-substituted dipyrromethane with similar or different substituted aromatic aldehydes, using cation exchange resins furnished meso-tetrakis-symmetrical and mixed porphyrins, respectively. One-pot synthesis of porphyrins can also be carried out directly from the aldehydes and pyrrole under the above conditions. Acidolysis of the dipyrromethane is negligible under the conditions of the porphyrin-forming reaction.

Full text of DOI:10.1016/S0040-4020(03)00245-X

Tetrahedron 59 (2003) 2207–2213
Facile synthesis of meso-substituted dipyrromethanes and
porphyrins using cation exchange resins
*
Rajan Naik, Padmakar Joshi, Sharada P. Kaiwar (nee Vakil) and Rajesh K. Deshpande
*
Department of Organic Chemistry (Synthesis), National Chemical Laboratory, Pune 411008, India
Received 1 November 2002; revised 21 January 2003; accepted 13 February 2003
Abstract—The macroporosity and acidity of cation exchange resins play a crucial role in the synthesis of dipyrromethanes and porphyrins;
for the first time, cation exchange resins have been used as heterogeneous solid acid catalysts to produce dipyrromethanes and porphyrins in
good yields. The reaction, at room temperature, of substituted aromatic aldehydes with pyrrole catalysed by cation exchange resin afforded
the corresponding meso-substituted dipyrromethane in yields ranging from 70 to 80%, indicating the broad scope of the reaction. Further, the
condensation of meso-substituted dipyrromethane with similar or different substituted aromatic aldehydes, using cation exchange resins
furnished meso-tetrakis-symmetrical and mixed porphyrins, respectively. One-pot synthesis of porphyrins can also be carried out directly
from the aldehydes and pyrrole under the above conditions. Acidolysis of the dipyrromethane is negligible under the conditions of the
porphyrin-forming reaction. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
sterically hindered or electron withdrawing groups have
been prepared by using BF3–etherate as the acid catalyst,
along with DDQ as oxidant in moderate yields.5 There have
been recent advances to improve the synthesis of
5,10,15,20-tetraaryl porphyrins, including solid state and
other modifications.6 However, these syntheses suffer from
purification problems and lead to low yields of the products.
One of the major disadvantages of the above methods is the
requirement of large amounts of corrosive, acidic and
environmentally harmful chlorinated solvents.
A multitude of structurally diverse porphyrins have been
synthesized as mimics for heme-dependent proteins during
the past three decades. The great majority of these are
embellished derivatives of the basic tetraphenylporphyrin
framework. Tetraphenylporphyrins have been widely
exploited in the development of porphyrin model systems.1
meso or 5-substituted dipyrromethanes are important
precursors for the synthesis of meso-substituted porphyrins,
expanded porphyrins and porphyrin analogues.2 These are
used as key building blocks in the synthesis of linear
porphyrin arrays. Several methods have been reported for
the synthesis of 5-substituted dipyrromethanes by the
condensation of an aldehyde and pyrrole using various
combinations of acids and solvents.3 All these reports claim
moderate yields of meso-substituted dipyrromethanes. Thus,
aldehydes and pyrrole readily undergo condensation using
homogeneous acid catalysts such as BF3·etherate, trifluoro-
acetic acid (TFA), propionic acid, etc., at room temperature
to yield meso-substituted dipyrromethanes along with
oligomeric by-products. The yields are reduced due to the
formation of oligomers and this calls for stringent
purification methods to remove the by-products.
In connection with our interest in the synthesis of porphyrins
we describe here for the first time, a facile efficient synthetic
strategy for preparing 5-substituted dipyrromethanes in
excellent yields using cation exchange resins as hetero-
geneous acid catalysts (Scheme 1). These dipyrromethanes
are subsequently transformed to symmetrical and mixed
porphyrins. We are also reporting here a simple, convenient
one-pot synthesis of symmetrical porphyrins by condensing
pyrrole with substituted aldehydes in the presence of cation
exchange resins as acid catalysts.
These resins are the functional resins with a styrene
divinylbenzene copolymer matrix having sulfonic acid
groups. Macroporous (or macroreticular) functional resins
(present on the market mostly as polystyrene crosslinked
with divinylbenzene) are isotropic materials formed by
chemically interconnected polymer chains, normally
insoluble in any conceivable solvent. Each resin particle
can be viewed as a mini reactor (vide infra) filled with a
solution of functional polymer chains with pendant arms
bearing sulfonic acid groups.7 Functional synthetic cation
exchange resins serve as efficient industrial heterogeneous
catalysts, potentially useful in the area of fine chemical
Cyclocondensation of aryl aldehydes with pyrrole in
propionic acid is one of the most common methods for the
synthesis of symmetrical 5,10,15,20-tetraaryl porphyrins4 in
low yields. Porphyrins in which the phenyl rings bear
Keywords: porphyrins; cation exchange resin; condensation.
*
Corresponding authors. Tel./fax: þ91-20-5893153;
e-mail: rnaik@dalton.ncl.res.in
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00245-X

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R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
Scheme 1.
Table 2. Synthesis of meso-substituted dipyrromethanes
synthesis. They offer an environment for the catalytic
reaction quite different from that of a free solution or the
surface of conventional heterogeneous catalysts based on
inorganic supports. The mechanism of ion exchanger
catalysed reaction in a non-aqueous environment is similar
to that operating for conventional heterogeneous catalysts
(adsorption–surface reaction–desorption). An important
consequence of the catalysis being a multiplet of sulfonic
acid groups is that it shows more than a proportional
dependence of the reaction rate on the concentration of
acidic centres. In this connection, the environment of a
catalytic site embedded in the polymer network can almost
be considered as a micro reactor.8
Compound number
R1
R2 R3 Resin Time (h) Yield (%)
1a
1b
H
OCH3
H
H
H
H
In-130
In-130
T-63
12
15
10
15
10
15
10
10
10
10
10
80
65
72
66
71
75
77
73
77
71
61
1c
H
Cl
H
Cl In-130
T-63
H
1d
Cl
In-130
T-63
T-63
T-63
T-63
T-63
1e
1f
1g
1h
H
F
CH3
NO2
NO2
H
H
H
H
H
H
H
Most of the dipyrromethanes are stable for more than 2
months in the purified form, upon storage at 08C in the
absence of light.
2. Results and discussion
2.1. Synthesis of meso-substituted dipyrromethanes
The use of macroporous cation exchange resins has the
advantages of controlled acidity due to site isolation of
sulphonic acid groups, high selectivity and purity of the
product due to trace side reactions and easy work-up
procedures, which was evidently proven by the reduction of
oligomer formation and the production of excellent yields of
meso-substituted dipyrromethanes (70–80% yield) in pure
forms. This refined process enabled the straightforward
preparation of multi-gram batches of 5-substituted dipyrro-
methanes. The yields of dipyrromethanes obtained in our
method are also much better than those in the existing
methods where homogeneous acid catalysts have been
employed.
The condensation of pyrrole with benzaldehyde in the
presence of various cation exchange resins afforded very
good yields of meso-phenyldipyrromethane (Scheme 1,
Table 1). Among the different polymeric cation exchange
resins used, T-63 and Indion-130 resins were found to be
more suitable with respect to the product yields, batch-to-
batch consistency and clean work-up. These resins are of
macroreticular type, having a styrene divinylbenzene
co-polymer matrix (15–17% crosslinking) and the
exchange capacity is in the range of 4.5–4.7 mequiv./g.
Dipyrromethanes (1a–h) were prepared by condensation of
substituted aromatic aldehydes in neat excess pyrrole (1:20)
(Scheme 1, Table 2). Most of the dipyrromethanes were
readily crystallized after removal of pyrrole. The identity of
the products was confirmed by comparing melting points
and NMR spectra with that of the reported compounds.
2.2. Formation of symmetrical meso-substituted
porphyrins and mixed porphyrins
The ‘2þ2 synthesis’ using dipyrromethanes as inter-
mediates, forms the backbone of the building block
approach towards the synthesis of porphyrins. We have
further extended our strategy of using cation exchange
resins as acid catalysts in the preparation of symmetrical and
mixed porphyrins incorporating various functional groups
from aryldipyrromethanes. One of our objectives has been
to develop a set of porphyrin building blocks that can be
combined in a rational manner to form multi-porphyrin
arrays and related porphyrin model systems. The cation
exchange resin-catalysed condensation of the aryl dipyrro-
methanes (1a–h) with aromatic aldehydes give rise to
porphyrinogens, which subsequently get oxidized to the
corresponding meso-substituted porphyrins (2) by means
of p-chloranil. With aromatic aldehydes having the
substituents as in (1), dipyrromethane give symmetrical
Table 1. Synthesis of meso- phenyldipyrromethane (1a) using various
resins
Entrya
Resin
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
Amberlyst-15
IR-120
Tulsion T-40
Tulsion T-42
Tulsion T-63
Indion-130
12
15
17
15
10
11
20
20
90
71
69
72
91
89
65
58
Amberlyte IR-100
Zeocarb 225
a
Entries 1–8 are strongly acidic cation exchange resins (Hþ form) having
a matrix structure with a styrene divinylbenzene copolymer functiona-
lised with sulfonic acid groups.

R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
2209
Scheme 2.
meso-porphyrins (Scheme 2, Table 3) and with different
aromatic aldehydes (mixed condensation) it furnishes trans
substituted mixed porphyrins (3) (Scheme 3, Table 4).
Table 3. Synthesis of 5,10,15,20-tetraarylporphyrins
Compound number
R1
R2
R3
Time (h)
Yield (%)
2a
2b
2c
2d
2e
2f
H
H
H
Cl
H
H
H
H
H
Cl
H
H
H
16
17
17
17
17
16
24
46
19
21
19
30
All the meso-substituted and mixed porphyrins have been
purified by column chromatography and characterized by
1H NMR, UV–vis and mass spectra.
OMe
H
Cl
F
CH3
2.3. One-pot synthesis of meso-substituted porphyrins
Cation exchange resin used is Indion-130.
One flask synthesis of porphyrins has also been carried out
Scheme 3.
without isolation of the dipyrromethane intermediate.
Reaction of pyrrole with substituted aromatic aldehydes
using cation exchange resin, in dichloromethane with
triethyl-orthoacetate gives meso-substituted porphyrins in
good yields (Scheme 4, Table 5). The procedure is mild,
clean and convenient.
Table 4. 5,15 Diaryl-10,20 diphenylporphyrins
Compound number
R1
R2
R3
Time (h)
Yielda (%)
3a
3b
3c
3d
3e
3f
OCH3
H
Cl
F
CH3
NO2
H
Cl
H
H
H
H
H
Cl
H
H
H
H
17
20
18
20
17
16
22
20
22
16
23
21
It has been observed that when the aldehyde contains an
electron donating substituent such as methoxy or methyl,
higher yields of porphyrins are obtained. However,
the reactions with aldehydes containing electron with-
drawing groups viz. 4-fluoro benzaldehyde, 2,6-dichloro
Cation exchange resin used is Indion-130.
a
Isolated yields.

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R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
Scheme 4.
Table 5. Synthesis of meso-tetrakis porphyrins (one-pot synthesis)
of analytical grade. Proton NMR spectra were recorded at a
frequency of AC 200 MHz with a Bruker instrument. Mass
spectra were obtained using a Finnigan Mat, 1020 Auto-
mated GC/MS with solid probe facility. For compounds
with higher molecular weights (800 and above), LSIMS
(FAB) spectra were obtained. Absorption spectra were
obtained using UV-1601 Shimadzu. Infra-red were obtained
using Shimadzu FTIR 8400 spectrophotometer. For Flash
Column Chromatography, SISCO silica gel (230–400
mesh) was used. TLC was performed with pre-coated
aluminium sheets with silica gel 60 F254. Cation-exchange
resins were procured from Thermax (India) Ltd., Pune and
Ion-Exchange India Ltd., Mumbai. The identities of all
known products were confirmed by comparison with their
physical and spectral data. Pyrrole was distilled at
atmospheric pressure from CaH2. CH2Cl2/CHCl3 were
distilled from K2CO3. The dipyrromethanes are easily
visualized upon exposure of thin layer chromatography
plates to Br2 vapour.
Compound number
R1
R2
R3
Time
(h)
Conc.
(mmol)
Yielda
(%)
2a
2b
H
H
H
H
H
16
16
17
17
17
17
17
17
16
6
10
6
10
10
6
10
10
10
33
64
46
60
22
18
23
20
68
OCH3
2c
2d
H
Cl
Cl
H
Cl
H
2e
2f
F
CH3
H
H
H
H
Cation exchange resin used is Indion-130.
a
Isolated yields.
benzaldehyde etc. result in lower yields of the product.
Similarly, as reported earlier,5b maximum yields are obtained
inone-pot condensationwhenthe reactionsarecarriedoutona
10 mmol scale. The workup is just mere filtration, removal of
the solvent and flash chromatography using silica gel.
4.2. General method for the preparation of meso-
substituted dipyrromethanes
It should be noted that the use of cation exchange resins as
heterogeneous catalysts is found to be superior to using
conventional, homogeneous acid catalysts in terms of purity
of the product, reduction in the amount of unwanted
polymeric by-products and ease of work-up.
A solution of benzaldehyde (10 mmol) and pyrrole
(200 mmol) was degassed by bubbling the mixture with
argon for 10 min. Cation exchange resin T-63 (5 g) was
added to this mixture. The solution was stirred at room
temperature. After the time indicated in Table 2, the
reaction mixture was diluted with CH2Cl2 (10 ml), 100 ml of
triethylamine was added to prevent acidolysis of the meso-
phenyl dipyrromethane and filtered. The filtrate was washed
with water and the organic layer was dried over Na2SO4.
The solvent was removed under reduced pressure and the
unreacted pyrrole was removed by vacuum distillation (5–
8 mm/30–358C). The resulting pale yellow amorphous solid
was purified by crystallization or flash chromatography
using pet. ether–ethylacetate–triethylamine (85:14:1) to
give dipyrromethanes as white crystals (70–80%).
3. Conclusion
Taking advantage of its macroporosity and acidity, a
versatile, novel, eco-friendly and simple protocol for the
synthesis of dipyrromethanes and porphyrins have been
achieved for the first time, using macroporous cation
exchange resins as catalysts.
4. Experimental
4.1. General
4.2.1. meso-Phenyldipyrromethane (1a).3e White crystals.
Yield 80%. Mp 1018C. 1H NMR (200 MHz, CDCl3):
d¼5.49 (s, 1H, mesoH), 5.92 (s, 2H), 6.18 (m, 2H), 6.72
All melting points are uncorrected. All chemicals used were

R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
2211
(m, 2H), 7.18–7.35 (m, 5H, ArH), 7.93 (brs, 2H, NH). MS
m/z (%): 222 (Mþ, 97), 194 (6), 179 (2), 165 (5), 154 (33),
145 (Mþ2C6H5, 100) 127 (14), 102 (7), 91 (19), 77 (20), 67
(15), 57 (25). Rf¼0.71 (0.5% MeOH in DCM).
(m, 2H). MS m/z (%): 267 (Mþ, 100), 251 (2), 236 (4), 220
(15), 201 (25), 191 (10), 163 (4), 154 (32), 145
(Mþ2C6H4NO2, 80), 127 (12), 117 (22), 104 (6), 89 (10),
75 (18), 67 (39). Rf¼0.62 (0.5% MeOH in DCM).
4.2.2. meso-(4-Methoxy)dipyrromethane (1b).3e Brownish-
white crystals. Yield 65%. Mp 98–998C. 1H NMR
(200 MHz, CDCl3): d¼3.78 (s, 3H, OCH3), 5.43 (s, 1H,
mesoH), 5.92 (m, 02H), 6.16 (dd, J¼2.9, 02.9 0Hz, 2H), 6.69
(m, 2H), 6.86 (AA BB0, m, 2H), 7.13 (AA BB , m, 2H), 7.92
(brs, 2H). MS m/z (%): 252 (Mþ, 94), 263 (7), 219 (6), 208
(10), 196 (7), 185 (14), 170 (38), 154 (19), 145
(Mþ2C7H7O, 100), 126 (17), 117 (30), 97 (23), 91 (46),
77 (36), 71 (55), 57 (100). Rf¼0.63 (0.5%MeOH in DCM).
4.2.3. meso-(2,6-Dichloro)dipyrromethane (1c).3e
Yellowish solid. Yield 66%. Mp 102–1038C. 1H NMR
(200 MHz, CDCl3): d¼6.06 (s, 1H, mesoH); 6.18 (dd,
J¼3.0, 3.0 Hz, 2H); 6.47 (s, 1H); 6.72–6.74 (m, 2H), 7.12
(t, J¼7.9 Hz, 2H), 7.32 (d, J¼7.9 Hz, 2H), 8.28 (bs, 2H,
NH). MS m/z (%): 290 (Mþ, 48), 264 (6), 253 (9), 238 (6),
224 (12), 188 (24), 174 (41), 159 (10), 145 (Mþ2C6H2Cl2,
100), 126 (15), 108 (23), 91 (12), 83 (65), 77 (32), 67 (45),
57 (30). Rf¼0.83 (0.5%MeOH in DCM).
4.3. General method for the synthesis of porphyrins 2a–f
and 3a–f
A mixture of meso-phenyl dipyrromethane (2 mmol) and
aldehyde (2 mmol) was stirred under a nitrogen atmosphere
in CH2Cl2 (50 ml) in presence of cation exchange resin (1 g)
at 258C for the corresponding time as mentioned in Tables 2
and 3. Chloranil (2 mmol) was then added and the reaction
mixture was further refluxed for 3 h, cooled and filtered. The
filtrate was concentrated and the crude product was
subjected to soxhlet purification using methanol. The
methanol insoluble product was then purified by flash
chromatography on silica gel to afford pink crystals of
porphyrins.
4.3.1. 5,10,15,20-Tetraphenylporphyrin (2a).6k Purple
crystals. Yield 24%. Mp .3008C. UV–vis (CH2Cl2) lmax
(nm) (1): 412 (90.0), 478 (8.1), 514 (42.2), 588 (12.9), 645
(10.7). 1H NMR (200 MHz, CDCl3): d¼-2.17 (s, 2H, NH),
7.74 (m, 12H, p- and m-Ph); 8.20 (d, J¼8.9 Hz, 8H, o-Ph);
8.84 (s, 8H, pyrrole-H). MS m/z (%): 614 (Mþ, 100), 538
(4), 458 (1), 308 (Mþ2C24H18, 11), 277 (3), 204 (1), 180
(6), 121 (12), 91 (19), 77 (14). Rf¼0.92 (0.5% MeOH in
DCM).
4.2.4. meso-(4-Chloro)dipyrromethane (1d).3m Pale-
1
yellow solid. Yield 77%. Mp 1128C. H NMR (200 MHz,
CDCl3): d¼5.46 (s, 1H, mesoH), 5.88 (m, 2H), 6.24 (m,
2H), 6.83 (m, 2H), 7.30 (m, 4H), 7.97 (brs, 2H, NH). MS m/z
(%): 256 (Mþ, 43), 190 (30), 145 (Mþ2C6H4Cl, 100), 91
(7), 71 (20). Rf¼0.85 (0.5% MeOH in DCM).
4.3.2. 5,10,15,20-(4-Methoxy) tetraphenylporphyrin
(2b).6k Purple crystals. Yield 46%. Mp .3008C. UV–vis
(CH2Cl2) lmax (nm) (1): 420 (78.6), 454 (7.6), 518 (6.0),
554 (4.7), 592 (2.3), 648 (2.6). 1H NMR (200 MHz, CDCl3):
d¼22.47 (brs, 2H, NH); 4.15 (s, 12H, OCH3); 7.31 (d,
J¼8.3 Hz, 8H, m-Ph), 8.11 (m, 8H, o-Ph), 8.51 (m, 8H,
pyrrole-H). MS m/z (%): 735 (Mþ, 36), 551 (20), 523 (14),
460 (76), 443 (18), 307 (Mþ2C28H28O4, 47), 289 (20), 154
(84), 137 (100), 120 (18), 107 (26), 91 (15), 77 (28), 55 (11).
Rf¼0.82 (0.5%MeOH in DCM).
4.2.5. meso-(2-Nitro)dipyrromethane (1e).3m Yellow
1
coloured liquid. Yield 73%. H NMR (200 MHz, CDCl3):
d¼5.86 (s, 1H, mesoH), 6.10–6.20 (m, 4H), 6.68–6.71 (m,
2H), 7.26–7.56 (m, 3H), 7.86–7.90 (m, 1H), 8.17 (brs, 2H,
NH). MS m/z (%): 267 (Mþ, 100), 251 (2), 236 (4), 220 (15),
201 (25), 191 (10), 163 (4), 154 (32), 145 (Mþ2C6H4NO2,
80), 127 (12), 117 (22), 104 (6), 89 (10), 75 (18), 67 (39).
Rf¼0.67 (0.5% MeOH in DCM).
4.2.6. meso-(4-Fluoro)dipyrromethane (1f).3e White
crystals. Yield 77%. Mp 81–828C. H NMR (200 MHz,
4.3.3. 5,10,15,20-(2,6-Dichloro) tetraphenylporphyrin
(2c).9a Purple crystals. Yield 19%. Mp.3008C. UV–vis
(CH2Cl2) lmax (nm) (1): 423 (525.2), 489 (18.8), 519 (67.7),
1
CDCl3): d¼5.49 (s, 1H, mesoH), 5.93 (m, 2H), 6.20 (dd,
J¼2.8, 2.8 Hz, 2H), 6.74 (m, 2H), 7.04 (m, 2H), 7.94 (m,
2H), 8.18 (brs, 2H, NH). MS m/z (%): 240 (Mþ, 100), 212
(6), 197 (1), 174 (70), 159 (80), 145 (Mþ2C6H4F, 45), 130
(5), 117 (10), 108 (4), 91 (24), 86 (12), 77 (6), 67 (10).
Rf¼0.75 (0.5% MeOH in DCM).
4.2.7. meso-(4-Methyl)dipyrromethane (1g).3e Buff
coloured solid. Yield 71%. Mp 110–1118C. 1H NMR
(200 MHz, CDCl3): d¼2.32 (s, 3H, Ar–CH3), 5.44 (s, 1H,
mesoH), 5.91 (m, 2H), 6.15 (m, 2H), 6.68 (m, 2H), 7.11 (m,
4H), 7.91 (brs, 2H, NH). MS m/z (%): 236 (Mþ, 15), 221
(Mþ2CH3, 3), 208 (3), 181 (3), 170 (24), 155 (20), 136 (5),
119 (34), 105 (7), 91 (51), 77 (19), 65 (32), 56 (100).
Rf¼0.71 (0.5% MeOH in DCM).
1
557 (45.8), 593 (22.2), 650 (22.6). H NMR (200 MHz,
CDCl3): d¼22.57 (s, 2H, NH), 7.72–7.87 (m, 12H),
8.71 (m, 8H, pyrrole-H). MS m/z (%): 890 (Mþ, 5), 735
(62), 551 (32), 523 (22), 460 (72), 443 (14), 307
(Mþ2C24H11Cl8, 44), 289 (20), 155 (100), 137 (98), 120
(18), 107 (24), 91 (16), 77 (30), 55 (13). Rf¼0.79 (0.5%
MeOH in DCM).
4.3.4. 5,10,15,20-(4-Chloro) tetraphenylporphyrin (2d).6k
Purple crystals. Yield 21%. Mp .3008C. UV–vis (CH2Cl2)
l
max (nm) (1): 485 (19.9), 515 (106.6), 550 (44.8). 1H NMR
(200 MHz, CDCl3): d¼22.16 (brs, 2H, NH); 7.76 (d,
J¼8.2 Hz, 8H, m-Ph); 8.14 (d, J¼8.2 Hz, 8H, o-Ph); 8.83 (s,
8H, pyrrole-H). MS m/z (%): 752 (Mþ, 44), 717 (Mþ2Cl,
8), 664 (9), 647 (7), 604 (Mþ2C6H5Cl2, 32), 577 (27), 551
(14), 524 (6), 495 (7), 467 (8), 439 (10), 339 (14), 327 (4),
313 (10), 289 (6), 281 (13), 263 (11), 243 (6), 219 (10), 207
(16), 185 (8), 176 (12), 165 (19). Rf¼0.90 (0.5% MeOH in
DCM).
4.2.8. meso-(4-Nitro) dipyrromethane (1h).3e Yellowish-
1
white solid. Yield 61%. Mp 1608C. H NMR (200 MHz,
CDCl3): d¼5.57 (s, 1H, mesoH), 5.86 (m, 2H), 6.17 (m,
2H), 6.74 (m, 2H), 7.35 (m, 2H), 8.03 (brs, 2H, NH), 8.13

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R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
4.3.5. 5,10,15,20-(4-Fluoro) tetraphenylporphyrin (2e).
Purple crystals. Yield 19%. Mp .3008C. UV–vis (CH2Cl2)
lmax (nm) (1): 416 (194.3), 428 (1.7), 513 (7.7), 548 (3.1),
589 (2.4), 644 (1.5). FT-IR nmax (cm21): 3303 (nNH), 2964
(nCH), 2850, 1600 (nC–C), 1502, 1377 (nC–C)methine
4.3.10. 5,15-Bis(4-fluorophenyl)-10,20-diphenyl por-
phyrin (3d). Purple crystals. Yield 16%. Mp .3008C.
UV–vis (CH2Cl2) lmax (nm) (1): 418 (15.8), 541 (2.0), 515
(2.3), 343 (3.9). FT-IR nmax (cm21): 3309 (nNH), 2923
(nCH), 2854, 1596 (nC–C), 1504, 1367 (nC–C)methine
1
1
bridge, 1126 (dCH), 1074 (dCH), 979 (dNH), 702 (gNH). H
bridge, 1155 (dCH), 1070 (dCH), 966 (dNH), 698 (gNH). H
NMR (200 MHz, CDCl3): d¼22.70 (brs, 2H, NH), 7.85
(d, J¼8.2 Hz, 8H), 8.17 (d, J¼8.2 Hz, 8H), 8.83 (s, 8H,
pyrrole-H). MS m/z (%): 687 (Mþ, 49), 551 (15), 524 (18),
495 (34), 468 (48), 440 (66), 419 (26), 411 (39), 383 (40),
355 (14), 307 (Mþ2C24H16F4, 100), 289 (63), 272 (13), 257
(22), 242 (13), 229 (15), 197 (12), 183 (30), 166 (34).
Anal. calcd for C44H26N4F4: C, 76.96; H, 3.79; N, 8.16.
Found C, 76.75; H, 3.93; N, 8.21. Rf¼0.91 (0.5% MeOH in
DCM).
NMR (200 MHz, CDCl3): d¼22.50 (s, 2H), 7.42 (m, 10H,
m- and p-Ph), 7.77 (m, 4H), 8.20 (m, 4H), 8.85 (m, 8H,
pyrrole-H). MS m/z (%): 650 (Mþ, 14), 603 (13), 551 (20),
523 (14), 460 (Mþ2C12H8F2, 76), 443 (18), 307
(Mþ2C24H17F2, 47), 289 (20), 154 (84), 137 (100). Anal.
calcd for C44H28N4F2: C 81.23; H, 4.31; N, 8.61. Found C,
80.96; H, 4.40; N, 8.81. Rf¼0.82 (0.5%MeOH in DCM).
4.3.11. 5,15-Bis(4-methylphenyl)-10,20-diphenylpor-
phyrin (3e).9c Purple crystals. Yield 23%. Mp .3008C.
UV–vis (CH2Cl2) lmax (nm) (1): 646 (0.7) 543.0 (0.9), 542
4.3.6. 5,10,15,20-(4-Methyl) tetraphenylporphyrin (2f).5e
Purple crystals. Yield 30%. Mp .3008C. UV–vis (CH2Cl2)
lmax (nm) (1): 419 (86.8), 485 (4.2), 517 (11.0), 553 (6.4),
592 (4.1), 648 (3.2). 1H NMR (200 MHz, CDCl3): d¼22.17
(brs, 2H, NH), 2.70 (s, 12H, CH3), 7.54 (m, 8H), 8.08 (m,
8H), 8.84 (s, 8H, pyrrole-H). MS m/z (%): 670 (Mþ, 24),
551 (18), 460 (18), 418 (11), 391 (13), 353 (11), 333 (14),
307 (Mþ2C28H27, 100), 289 (71), 278 (14), 259 (16), 241
(17), 228 (22), 218 (17), 204 (16), 194 (21), 180 (29), 167
(37). Rf¼0.90 (0.5% MeOH in DCM).
1
(1.3), 517 (2.9), 419 (62.1). H NMR (200 MHz, CDCl3):
d¼22.80 (brs, 2H, NH), 2.70 (s, 6H, CH3), 7.53 (4H, d,
J¼7.8 Hz, 5,15 Ar-3,5H), 7.76 (6H, m, 10,20 Ar-3,4,5H),
8.11 (4H, m, 10,20-Ar-2,6H), 8.21 (4H, m, 5,15-Ar-2,6H)
and 8.83 (8H, m, pyrrole-H). MS m/z (%): 642 (Mþ, 7), 493
(2), 434 (2), 385 (4), 311 (9), 270 (14), 231 (9), 185 (11),
148 (16), 91 (Mþ2C39H27N4, 30), 77 (28), 51 (100).
Rf¼0.82 (0.5% MeOH in DCM).
4.3.12. 5,15-Bis(4-nitrophenyl)-10,20-diphenyl por-
phyrin (3f).9d Purple crystals. Yield 21%. Mp .3008C.
UV–vis (CH2Cl2) lmax (nm) (1): 416 (90.0), 514 (5.6), 548
4.3.7. 5,15-Bis(4-methoxyphenyl)-10,20-diphenylpor-
phyrin (3a).9b Purple crystals. Yield 22%. Mp .3008C.
UV–vis (CH2Cl2) lmax (nm) (1): 420 (112.9), 452 (17.8),
516 (6.7), 552 (3.8), 590 (2.1); 1H NMR (200 MHz, CDCl3):
d¼22.59 (s, 2H, NH), 4.16 (s, 6H, OCH3), 7.25 (m, 4H),
7.51–7.55 (m, 6H), 7.97 (m, 8H); 8.58 (s, 8H, pyrrole-H).
MS m/z (%): 674 (Mþ, 78), 307 (Mþ2C26H23O2, 33), 243
(6), 154 (100), 107 (26), 89 (25), 83 (10), 77 (28), 69 (17),
55 (24). Rf¼0.79 (0.5% MeOH in DCM).
1
(2.6), 590 (1.8), 648 (1.4). H NMR (200 MHz, CDCl3):
d¼22.56 (brs, 2H, NH), 7.76 (m, 10H), 8.19 (m, 8H), 8.84
(s, 8H, pyrrole-H). MS m/z (%): 704 (Mþ, 7), 664 (11), 647
(7), 313 (4), 281 (5), 252 (5), 227 (3), 207 (8), 165 (10), 154
(28), 133 (61), 105 (32), 91 (Mþ2C37H21N6O4, 45), 77
(60), 57 (100). Rf¼0.78 (0.5% MeOH in DCM).
4.4. General method for one-pot condensation of pyrrole
and aldehydes
4.3.8. 5,15-Bis(2,6-dichlorophenyl)-10,20-diphenyl-
porphyrin (3b).9c Purple crystals. Yield 20%. Mp
.3008C. UV–vis (CH2Cl2) lmax (nm) (1): 218 (4.3), 375
(7.7), 484 (1.0), 515 (5.9), 550 (2.0), 591 (1.7), 646 (1.0). 1H
NMR (200 MHz, CDCl3): d¼22.16 (brs, 2H, NH), 7.73–
7.78 (m, 12H, p- and m-Ph), 8.20 (m, 4H, o-Ph), 8.85 (s, 8H,
pyrrole-H). MS m/z (%): 752 (Mþ, 14), 683 (Mþ22Cl,
100), 615 (76), 566 (6), 492 (3), 444 (3), 380 (9), 342 (44),
306 (Mþ2C24H16Cl2, 21), 256 (11), 210 (14), 154 (17), 77
(34). Rf¼0.80 (0.5% MeOH in DCM).
To a degassed solution of dry DCM (400 ml) was added
aldehyde (10 mmol). After stirring for 10 min under
nitrogen, pyrrole (10 mmol) was added dropwise with
continuous stirring followed by cation exchange resin
T-63 (4.5 g) and triethylorthoacetate (10 mmol). After
16–17 h of stirring at room temperature, chloranil
(10 mmol) was added and the reaction mixture refluxed
for 2 h. The mixture was filtered and the filtrate con-
centrated. The crude product was purified by flash
chromatography using silica gel to obtain purple crystals
of porphyrins.
4.3.9. 5,15-Bis(4-chlorodiphenyl)-10,20-diphenylpor-
phyrin (3c). Purple crystals. Yield 21%. Mp .3008C.
UV–vis (CH2Cl2) lmax (nm) (1): 215 (11.6), 591 (4.1), 550
(5.7), 576 (13.5), 487 (2.7). FT-IR: nmax (cm21): 3319
(nNH), 3018 (nCH), 2927, 2399, 1596 (nC–C), 1350 (nC–
C)methine bridge, 1180 (dCH), 1089 (dCH), 966 (dNH), 700
4.4.1. meso-Tetraphenyl porphyrin (2a).6k Purple crys-
tals. Yield 33% when 6-mmol batch was performed. Purple
crystals. Yield 64% when 10-mmol batch was performed.
1
(gNH). H NMR (200 MHz, CDCl3): d¼22.55 (brs, 2H,
NH), 7.72–7.76 (m, 6H, m- and p-Ph), 7.97–8.01 (m, 4H,
o-Ph), 8.12–8.23 (m, 4H), 8.59 (m, 4H), 8.85 (s, 8H,
pyrrole-H). MS m/z (%): 684 (Mþ, 23), 649 (Mþ2Cl, 36),
495 (7), 460 (10), 329 (6), 307 (Mþ2C24H18Cl2, 24), 289
(13), 259 (8), 217 (94), 154 (100), 136 (75), 107 (27), 90
(26), 77 (28), 53 (8). Anal. calcd for C44H28N4Cl2: C, 77.31;
H, 4.10; N, 8.20. Found C, 77.24; H, 4.36; N, 8.05. Rf¼0.83
(0.5%MeOH in DCM).
4.4.2. meso-Tetrakis (4-methoxy) phenylporphyrin
(2b).6k Purple crystals. Yield 46% when 6-mmol batch
was performed. Purple crystals. Yield 60% when 10-mmol
batch was performed.
4.4.3. meso-Tetrakis (2,6-dichloro) phenylporphyrin
(2c).9a Purple crystals. Yield 22% when 10-mmol batch
was performed.

R. Naik et al. / Tetrahedron 59 (2003) 2207–2213
2213
4.4.4. meso-Tetrakis (4-chloro) phenylporphyrins (2d).6k
Purple crystals. Yield 18% when 6-mmol batch was
performed. Purple crystals. Yield 23% when 10-mmol
batch was performed.
Chem. Ber. 1994, 127, 223–229. (m) Vigmond, S. J.; Chang,
M. C.; Kallury, K. M. R.; Thompson, M. Tetrahedron Lett.
1994, 35, 2455–2458. (n) Nishino, N.; Wagner, R. W.; Lindsey,
J. S. J. Org. Chem. 1996, 61, 7534–7544. (o) Wijesekera, T. P.
Can. J. Chem. 1996, 74, 1868–1871. (p) Setsune, J.;
Hashimoto, M.; Shiozawa, K.; Hayakawa, J.; Ochi, T.; Masuda,
R. Tetrahedron 1998, 54, 1407–1424.
4.4.5. meso-Tetrakis (4-fluoro) phenylporphyrin (2e).
Purple crystals. Yield 20% when 10-mmol batch was
performed.
4. (a) Adler, A. D.; Longo, F. R.; Shergalis, W. D. J. Am. Chem.
Soc. 1964, 86, 3145–3149. (b) Adler, A. D.; Longo, F. R.;
Finarelli, J. D.; Goldnacher, J.; Assour, J.; Korsakoff, L. J. Org.
Chem. 1967, 32, 476. (c) Adler, A. D.; Saklar, L.; Longo, F. R.;
Finarelli, J. D.; Finurelli, G. M. J. Heterocycl. Chem. 1968, 5,
669–678. (d) Kim, J. B.; Adler, A. D.; Longo, F. R. J. Am.
Chem. Soc. 1972, 94, 3986–3992.
4.4.6. meso-Tetrakis (4-methyl) phenylporphyrin (2f).5e
Purple crystals. Yield 68% when 10-mmol batch was
performed.
Acknowledgements
5. (a) Lindsey, J. S.; Schreiman, I. C.; Hsu, H. C.; Kearney, P. C.;
Marguerettaz, A. M. J. Org. Chem. 1987, 52, 827–836.
(b) Lindsey, J. S.; Schreiman, I. C. Tetrahedron Lett. 1986,
27, 4969–4970. (c) Lindsey, J. S.; Wagner, R. W. J. Org. Chem.
1989, 54, 828–836. (d) Swanson, K. L.; Snow, K. M.;
Jeyakumar, D.; Smith, K. M. Tetrahedron 1991, 47,
685–696. (e) Rocha Gonsalves, A. M. A.; Varejo, M. T. B.;
Pereira, M. M. J. Heterocycl. Chem. 1991, 28, 685–695.
(f) Drain, C. M.; Gong, X. J. Chem. Commun. 1997,
2117–2118.
We are grateful to Dr K. N. Ganesh for his encouragement.
We thank Thermax (India) Ltd. and Ion Exchange (India)
Ltd., Mumbai, for the supply of cation exchange resins. We
are also thankful to DST, New Delhi, for financial support.
SPK is grateful to CSIR, New Delhi, for senior research
associateship.
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