Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes with N-tosyl imines

Article abstract of DOI:10.1016/j.tet.2009.01.009

A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the porphyrinogen to porphyrin. The method was applied to the synthesis of trans-A₂B₂-tetraarylporphyrins and the products were obtained with only a trace amount of one scrambling product. The synthesis of two important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in '2+2' porphyrin formation reactions is presented.

Full text of DOI:10.1016/j.tet.2009.01.009

Tetrahedron 65 (2009) 2043–2050
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of meso-tetraphenyl porphyrins via condensation of dipyrromethanes
with N-tosyl imines
*
Baris Temelli, Canan Unaleroglu
Hacettepe University, Department of Chemistry, 06800 Ankara, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
A new synthetic route for the synthesis of 5,10,15,20-tetraphenyl porphyrins has been developed based
on the reaction of 5-substituted dipyrromethanes with N-tosyl imines in the presence of a metal triflate
catalyst. meso-Substituted tetraphenyl porphyrins were synthesized in a two-step process. The first step
of the method is the metal triflate-catalyzed condensation of 5-substituted dipyrromethanes with N-
tosyl imines to form a porphyrinogen intermediate and the second step is the oxidation of the por-
phyrinogen to porphyrin. The method was applied to the synthesis of trans-A2B2-tetraarylporphyrins and
the products were obtained with only a trace amount of one scrambling product. The synthesis of two
important building blocks for porphyrin synthesis, mono and di-sulfonamide alkylated 5-substituted
dipyrromethanes, was achieved by the addition of 5-substituted dipyrromethane to N-tosyl imine. The
application of mono and di-sulfonamide alkylated 5-substituted dipyrromethanes in ‘2þ2’ porphyrin
formation reactions is presented.
Received 15 September 2008
Received in revised form 2 December 2008
Accepted 5 January 2009
Available online 8 January 2009
Keywords:
Porphyrin
Dipyrromethane
Metal triflate
N-Tosyl imine
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
such as using clays10 and transition metal salts as catalyst,11 the
yields are low and there are still some purification problems.
Porphyrins are a class of naturally occurring macrocyclic com-
pounds, which play a very important role in the metabolism of
living organisms.1 Porphyrins and their metal complexes have been
the subject of various studies and find application as photosensi-
tizers in photodynamic therapy and boron neutron capture ther-
apy,2 catalysts,3 sensors4 and molecular electronic devices.5
Among the great variation of porphyrins with a specific pattern
of substituents, the most widely studied synthetic porphyrin group
encompasses the symmetrical 5,10,15,20-tetraarylporphyrins like
5,10,15,20-tetraphenylporphyrin (TPP) (A4-type porphyrin), be-
cause of their potential applications in materials chemistry.6 This
type of porphyrin was first synthesized by the condensation of
benzaldehyde and pyrrole in pyridine at high temperatures by
Rothemund.7 Adler later developed this method by using propionic
acid or acetic acid as solvent,8 however, the method fails with al-
dehydes bearing acid sensitive functional groups. This problem was
solved with a new method developed by Lindsey who used BF3-
etherate as a catalyst in the synthesis of porphyrinogen and oxi-
dized it to porphyrin with DDQ.9 Although some improvements
have been reported for the synthesis of meso-tetraarylporphyrins
meso-Substituted trans-A2B2-tetraarylporphyrins are also
important components found in many applications of biomimetic
and materials chemistry.12 The synthetic methods for trans-A2B2-
tetraarylporphyrins suffer from rearrangement of substituents on
porphyrins, the so-called ‘scrambling’, and the need for extensive
chromatography to isolate trans-A2B2-tetraarylporphyrins from the
mixture of porphyrins. Steric and electronic factors, reagent con-
centration and type of acid catalyst influence the formation of
scrambled products.13 Therefore, porphyrin synthesis without
scrambling is a challenge for synthetic chemists.
Aminomethylpyrrole and aminomethyl-dipyrromethane de-
rivatives have been used in porphyrin synthesis as in the self-con-
densation of aminomethylpyrroles14 or in the condensation of
bis(aminomethyl)dipyrromethanes or bis(aminomethyl)pyrroles
with pyrrole derivatives.15 The synthesis of meso-substituted por-
phyrins has been restricted to trans-AB and trans-A2 porphyrins
when Mannich reagents (CH2¼NR2X) are used for the synthesis of
aminomethylpyrrole and aminomethyl-dipyrromethane derivatives.
This limitation has directed us to investigate a new reaction route
allowing a possibility for the synthesis of meso-tetraarylporphyrins
through the reaction of 5-substituted dipyrromethanes with
N-tosyl imines. According to our knowledge, the only example
of aminomethylation reaction in A4-porphyrin synthesis is the
preparation of meso-tetraalkyl porphyrin derivatives in low yields
and very long reaction time by the reaction of pyrrole with
Schiff bases.16
* Corresponding author. Hacettepe University, Department of Chemistry, Beytepe
Campus, 06800 Ankara, Turkey. Tel.: þ90 312 297 7962; fax: þ90 312 299 2163.
E-mail address: canan@hacettepe.edu.tr (C. Unaleroglu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.01.009

2044
B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
Recently, our studies on the alkylation of pyrrole17 and synthesis
catalysts. The catalytic activity of metal triflates was first tested on
a model reaction (Scheme 2). The synthesis of meso-substituted
porphyrins from the reaction of 5-phenyldipyrromethane (1a) and
N-benzylidene-4-methylbenzenesulfonamide (2a) was examined
by taking 10 mM concentration of each reactant in the presence of
10 mol % of metal triflate catalyst in CH2Cl2 at room temperature.
The reaction was monitored with TLC and 5,10,15,20-tetraphe-
nylporphyrin (TPP) (3a) was purified by flash column chromato-
graphy after work-up. Gd, Yb and Zn-triflates were found inefficient,
while Y, La and Nd-triflates catalyzed the reaction but with low
yield (Table 1, entries 1–6). The highest yield of TPP was obtained
with Cu(OTf)2 catalyst as 44% (Table 1, entry 9). The effect of the
amount of Cu(OTf)2 (2–20 mol %) on the yield was then examined.
The yield was increased up to 44% with 10 mol % of the catalyst
(Table 1, entries 7–9). Higher amounts of Cu(OTf)2 resulted in lower
yields (Table 1, entries 10 and 11).
of 5-substituted dipyrromethanes18 by using N-tosyl imines
showed that metal triflates are attractive Lewis acid catalysts for
the preparation of porphyrinic macrocyles. Although several types
of metal triflate-catalyzed organic reactions have been published so
far,19 only a few examples in porphyrin synthesis have been
reported.20,21
Herein, we report a new route for the synthesis of 5,10,15,20-
tetraphenyl porphyrins and trans-A2B2-tetraarylporphyrins by the
reaction of 5-substituted dipyrromethanes with N-tosyl imines in
the presence of a metal triflate catalyst. A one-flask, two-step re-
action was chosen for the reaction protocol as in the Lindsey
method. The first step of the method is the metal triflate-catalyzed
condensation of 5-substituted dipyrromethanes with N-tosyl im-
ines to form porphyrinogen intermediate and the second step is the
oxidation of porphyrinogen to porphyrin (Scheme 1). The study
involves the determination of favourable reaction conditions for
condensation and oxidation steps by investigating the effects of
various parameters.
The effect of solvent was examined by performing the reaction in
different organic solvents, like CH3CN, acetone, THF, Et2O, DCM,
CHCl3 and toluene, in the presence of 10 mol % Cu(OTf)2 at room
R1
R1
R1
NH
N
HN
HN
N
Ts
NH
NH
N
[O]
M(OTf)x
R2
R2
R2
+
R2
C
R2
HN
NH
H
HN
R1
R1
Scheme 1.
Ts
H
N
C
N
NH
1) 10 mol% M(OTf)x, DCM
2) DDQ
+
NH HN
N
HN
1a
2a
3a
Scheme 2.
Table 1
Effects of metal triflates type and the amount of catalyst on the synthesis of 3aa
It is known that 5-substituted dipyrromethanes have been
used as important building blocks in the synthesis of porphyrins in
‘2þ2’ MacDonald synthesis, which is a useful strategy for preparing
less symmetrical porphyrins by the condensation of dissimilar
dipyrromethanes.22 In this work, we also present the metal triflate-
catalyzed preparation of mono and di-sulfonamide alkylated
5-substituted dipyrromethane intermediates and their application
in ‘2þ2’ porphyrin formation.
Entry
Catalyst
Amount of
Yieldb (%) of 3a
Catalyst (mol %)
1
2
3
4
5
6
7
8
Gd(OTf)3
Yb(OTf)3
Y(OTf)3
10
10
10
10
10
10
2
d
d
30
2
La(OTf)3
Zn(OTf)2
Nd(OTf)3
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
d
4
11
20
44
25
10
5
2. Results and discussion
9
10
11
10
15
20
We attempted to synthesize meso-substituted porphyrins by the
reaction of 5-phenyldipyrromethane (1a) with N-benzylidene-4-
methylbenzenesulfonamide (2a) in the presence of metal triflate
a
Reaction conditions: (1) 10 mM of 1a and 2a, CH2Cl2, rt, 2 h; (2) DDQ.
Yield refers to pure product after column chromatography.
b

B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
2045
Table 3
temperature. The yield was highest (44%) in DCM among all the
The synthesis of 3a by using different catalystsa
solvents. To investigate the effect of oxidant, the oxidation step of the
reaction was repeated by using p-chloranil and o-chloranil as oxi-
dants, and by refluxing the reaction mixture in open air without
oxidant, however, high TPPyieldscould not be obtained as with DDQ.
One of the most important reaction parameters of the porphyrin
formation reactions is the reactant concentrations. The reactant
concentrations were examined over the range from 1 mM to
100 mM (Table 2, entries 1–7). TPP yield increased with the in-
creasing concentration of reactants up to 10 mM and no formation
was observed at 1 mM. The maximum yield of TPP (44%) was
obtained when 10 mM of each reactants was used (Table 2, entry 4).
According to the literature knowledge, porphyrinogen forms
with a reversible process in the first step of the reaction.9a,b,23
Therefore, we next optimized the reaction time to reach the
maximum amount of porphyrinogen for subsequent oxidation to
porphyrin (Table 2, entries 8–12). The maximum chemical yield
(45%) was obtained in 1.5 h (Table 2, entry 10).
On the basis of these studies, the best conditions for porphyrin
formation have been determined as the condensation of 10 mM of
dipyrromethane and N-tosyl imine with 10 mol % Cu(OTf)2 in
dichloromethane for 1.5 h and then oxidation with DDQ at room
temperature. The critical role of the catalyst in porphyrin synthesis
prompted us to examine other well-known Lewis acids or protic
acids in our model reaction and compare their activities with metal
triflates (Table 3, entries 1–9). Four of the examined acids listed in
Table 3 (CuCl2, SnCl4, TiCl4 and BF3-etherate) did not provide TPP at
all. Trichloroacetic acid, HCl, AlCl3 and p-toluenesulfonic acid yiel-
ded the product with low yield (3–13%). Only trifluorosulfonic acid
among the examined acids catalyzed the reaction by providing 39%
yield of TPP (Table 3, entry 5).
Entry
Catalyst
Yieldb (%) of 3a
1
2
3
4
5
6
7
8
9
p-CH3C6H4SO3H
CuCl2
AlCl3
13
d
11
5
39
3
d
d
d
HCl
CF3SO3H
Cl3CCOOH
SnCl4
TiCl4
BF3-etherate
a
Reaction conditions: (1)10 mM of 1a and 2a, catalyst (10 mol %), CH2Cl2, rt, 1.5 h;
(2) DDQ.
b
Yield refers to pure product after column chromatography.
Cu(OTf)2 and trans-A2B2-tetraarylporphyrins (4a–e) were obtained
in 18–30% yield (Table 5). The compounds were characterized by
NMR, FTIR and UV spectroscopy. MALDI-TOF experiments have been
performed to detect the presence of scrambled porphyrins in the
condensation reactions. Trace quantity of meso-A3B-type porphyrin
was detected while no other scrambled porphyrins were observed.
MALDI-TOF spectrum of 5,15-bis-(4-chlorophenyl)-10,20-diphenyl-
porphyrin (4d) is shown as a representative in Figure 1.
After the synthesis of meso-substituted tetraarylporphyrins by
direct condensation of 5-substituted dipyrromethanes with N-tosyl
imines (Scheme 3, route A), we applied MacDonald’s-type ‘2þ2’
approaches to our system using routes B and C (Scheme 3).
For this purpose sulfonamidealkyldipyrromethane and
bis(sulfonamidealkyl)dipyrromethane, 5 and 6, were synthesized
by changing the ratio of reactants in the addition reaction of 5-
phenyldipyrromethane (1a) to N-benzylidene-4-methylbenzene-
sulfonamide (2a) in the presence of 10 mol % of Cu(OTf)2 (Scheme
4). When an excess amount of dipyrromethane was used at 0 ꢀC,
sulfonamidealkyldipyrromethane product 5 was obtained in 60%
yield. Besides the main product, a side product was isolated in 10%
yield and identified as meso-substituted bilane 7. A similar reaction
was performed with excess amount of N-tosyl imine at ꢁ20 ꢀC and
the reaction afforded bis(sulfonamidealkyl)dipyrromethane and
sulfonamidealkyldipyrromethane, 6 and 5, in 68% and 10% yields,
respectively.
Applying the optimum reaction conditions, various N-tosyl im-
ines and 5-substituted dipyrromethanes were reacted to give the
corresponding A4-type meso-substituted porphyrins as summa-
rized in Table 4. The yield of porphyrin was considerably affected by
the nature and position of the substituents. Higher yields were
obtained with electron donating 4-methoxy or 4-methyl sub-
stituents present at para positions to phenyl groups than with
electron withdrawing trifluoromethyl and halogens (Table 4, en-
tries 1, 2,
4 and 7–10). 2-Methoxy, 2-hydroxy and 4-nitro
The synthesized compounds 5 and 6 were subjected to conden-
sation reactions under optimized reaction conditions (Scheme 3).
TPP (3a) was obtained in 42% yield by self-condensation reaction of
sulfonamidealkyldipyrromethane 5 (Scheme 3, route B) and in 18%
yield by the condensation of bis(sulfonamidealkyl)dipyrromethane
6 with 5-phenyldipyrromethane (Scheme 3, route C). These results
have directed us to suggest that the porphyrin formation mecha-
nism in the reaction of dipyrromethanes with N-tosyl imines pro-
ceeds through the formation of sulfonamidealkyldipyrromethane
and its self-condensation in the reaction medium.
substituted dipyrromethanes did not yield the expected porphyrin
product. The products were purified by flash column chromatog-
raphy and characterized by NMR, FTIR and UV–vis spectroscopy. All
the spectroscopic data for 3a,b,d,h–j are in full agreement with the
structures of the porphyrin compounds.24
We also examined whether the condensation of dipyrro-
methanes and N-tosyl imines could be applied to unsymmetrical
porphyrins. Therefore, we extended our work to the synthesis of
trans-A2B2-tetraarylporphyrins. 5-Phenyldipyrromethane (1a) was
reacted with different N-tosyl imines in the presence of 10 mol %
Table 2
3. Conclusion
Effect of concentrations of reactants and reaction time on the synthesis of 3aa
Entry
Molarity [mM] of reactants
Reaction time (h)
Yieldb (%) of 3a
In conclusion, a new metal triflate-catalyzed, one-flask two-step
meso-substituted porphyrin synthesis has been achieved by the
reaction of 5-substituted dipyrromethanes and N-tosyl imines. This
method introduces an alternative route to the existing methodo-
logies by offering several advantages including (i) mild reaction
conditions, (ii) reasonably good yields and (iii) only trace amount of
scrambling product in trans-A2B2-tetraarylporphyrins. In addition,
two important building blocks, mono and dialkylated 5-substituted
dipyrromethanes, were also synthesized and used in different
MacDonald-type ‘2þ2’ condensation reactions. The convenient
availability of these intermediates makes possible to extend this
methodology also to the synthesis of tetraarylporphyrins with
different aryl groups for further studies.
1
2
3
4
5
6
7
8
1
3.2
5.6
10
17.8
31.6
100
10
10
10
10
10
2
2
2
2
2
2
2
0.5
1
0
23
30
44
29
23
11
24
32
45
38
26
9
10
11
12
1.5
2.5
3
a
Reaction conditions: (1) 10% Cu(OTf)2, CH2Cl2, rt; (2) DDQ.
Yield refers to pure product after column chromatography.
b

2046
B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
Table 4
Effect of the substituents on the synthesis of meso-tetraphenyl porphyrinsa
R1
R2
R1
Ts
R2
R2
N
C
NH
N
N
1) 10 mol% Cu(OTf)2, DCM
2) DDQ
R1
R1
R2
H
+
HN
R2
R1
HN
NH
R2
2a-j
1a-j
R1
3a-j
Entry
Compound
R1
R2
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
OCH3
H
CH3
H
NO2
CF3
F
H
H
OCH3
H
OH
H
H
H
H
H
45
44
d
35
d
d
25
13
31
29
Cl
Br
3j
a
Reaction conditions: (1) 10 mM of reactants, 10% Cu(OTf)2, CH2Cl2, rt, 1.5 h; (2) DDQ.
Yield refers to pure product after column chromatography.
b
4. Experimental
4.1. General
absorption spectra were measured using a Jasco V-530 UV–vis
spectrophotometer. Elemental analysis experiments were per-
formed by LECO CHNS. Melting points were recorded on Gallen-
kamp melting-point apparatus. Reactions were monitored by thin-
layer chromatography using 60F silica gel plates. Flash column
chromatography was performed on silica gel 60 F254 (230–400
Commercially available reagents and solvents were used with-
out further purification. 1H NMR (400 MHz) and 13C NMR
(100 MHz) spectra were recorded using SiMe4 as an internal ref-
erence with Bruker Ultrashield FT NMR spectrometer. Coupling
constants are expressed as J values in hertz. Infrared spectra were
taken by Unicam Mattson 1000 FTIR Spectrophotometer. Electronic
mesh). The spots were visualized with UV light (l¼254 nm). N-Tosyl
imines (2a–j) are synthesized in high yields by the reaction of p-
toluenesulfonamide and aldehydes in the presence of p-toluene-
sulfonic acid. 5-Substituted dipyrromethanes are synthesized
Table 5
The synthesis of meso-substituted-trans-A2B2-tetraarylporphyrinsa
Ts
N
NH
N
N
1) 10 mol% Cu(OTf)2, DCM
C
R
R
H
2) DDQ
+
HN
R
HN
NH
1a
4a-e
Entry
Compound
R
Yieldb (%)
1
2
3
4
5
4a
4b
4c
4d
4e
OCH3
CH3
NO2
Cl
22
30
18
27
30
Br
a
Reaction conditions: (1) 10 mM of reactants, 10% Cu(OTf)2, CH2Cl2, rt, 1.5 h; (2) DDQ.
Yield refers to pure product after column chromatography.
b

B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
2047
dichloromethane (3ꢂ10 mL). The combined organic phases were
dried over magnesium sulfate and the solvent was evaporated
under reduced pressure. The crude product was purified by col-
umn chromatography with dichloromethane.
4.2.1. 5,10,15,20-Tetraphenylporphyrin (3a)
Purple crystals; mp >300 ꢀC; yield: 138 mg, 45%; spectroscopic
data are identical to that reported in the literature.24a
4.2.2. 5,10,15,20-Tetrakis(4-methoxyphenyl)porphyrin (3b)
Purple crystals; mp >300 ꢀC; yield: 162 mg, 44%; spectroscopic
data are identical to that reported in the literature.24a
4.2.3. 5,10,15,20-Tetrakis(4-methylphenyl)porphyrin (3d)
Purple crystals; mp >300 ꢀC; yield: 117 mg, 35%; spectroscopic
data are identical to that reported in the literature.24a
4.2.4. 5,10,15,20-Tetrakis(4-trifluoromethylphenyl)porphyrin (3g)
Purple crystals; mp >300 ꢀC; yield: 111 mg, 25%; Rf 0.95
(CH2Cl2); UV–vis lmax (CH2Cl2) (log 3): 416 (3.9), 512 (4.4), 546 (3.9),
Figure 1. MALDI-TOF spectrum of 5,15-bis-(4-chlorophenyl)-10,20-diphenyl-porphy-
rin (4d).
588 (3.8), 644 (3.6); IR (KBr): 3312, 3044, 2929, 1614, 1557, 1477,
1405, 1322, 1165, 1125, 1067, 1019, 967, 854, 796, 727, 680,
according to the literature procedure.18 MALDI-TOF spectra were
recorded on Applied Biosystems Voyager DE Pro by using 2,5-
dihydroxybenzoic acid matrix.
605 cmꢁ1
;
1H NMR (400 MHz, CDCl3):
d
ꢁ2.70 (br s, 2H, NH), 8.08
(d, J¼8.2, 8H, m-PhH), 8.37 (d, J¼8.0, 8H, o-PhH), 8.85 (s, 8H, pyr-
role-H); 13C NMR (100 MHz, CDCl3):
d
119.0, 123.8 (q, JC–F¼3.6),
3
124.5 (q, 1JC–F¼270.5), 130.4 (q, 2JC–F¼32.5), 131.3 (br s), 134.6, 145.5.
Anal. Calcd for C44H30N4: C, 65.02; H, 2.96; N, 6.32. Found: C, 65.38;
H, 2.75; N, 6.43.
4.2. General procedure for the synthesis of meso-substituted
porphyrins 3a–j and 4a–e
A
solution of N-tosyl imine (1 mmol) and metal triflate
4.2.5. 5,10,15,20-Tetrakis(4-fluorophenyl)porphyrin (3h)
Purple crystals; mp >300 ꢀC; yield: 45 mg, 13%; spectroscopic
data are identical to that reported in the literature.24a
(0.1 mmol) in dichloromethane (50 mL) was stirred for 30 min at
room temperature under nitrogen atmosphere. A solution (50 mL)
of dipyrromethane (1 mmol) in dichloromethane was added
dropwise into the reaction mixture shielded from light with alu-
minium foil. After 1.5 h, DDQ (1.5 mmol) was added and the re-
action mixture was further stirred for 2 h. Water (10 mL) was
added to the mixture and aqueous phase was extracted with
4.2.6. 5,10,15,20-Tetrakis(4-chlorophenyl)porphyrin (3i)
Purple crystals; mp >300 ꢀC; yield: 117 mg, 31%; spectroscopic
data are identical to that reported in the literature.24a
Route A
Ts
N
+
C
H
Route B
Route C
HN
NH
1a
2a
1) 10% Cu(OTf)2
2) DDQ
HN
NH
HN
NH
1)
10% Cu
2) DDQ
2
HN
Ts
NH
Ts
HN
Ts
(OTf)
2
5
6
1) 10% Cu(OTf)
2) DDQ
+
HN
NH
NH
N
N
HN
3a
Scheme 3.

2048
B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
3 equiv. 1a
NH HN
HN
HN
NH
+
0 °C
HN
Ts
NH
HN
NH
5
7
1a
10% Cu(OTf)2
+
Ts
H
N
C
3 equiv. 2a
-20 °C
+
HN
NH
NH
HN
NH
2a
HN
Ts
HN
Ts
Ts
6
5
Scheme 4.
4.2.7. 5,10,15,20-Tetrakis(4-bromophenyl)porphyrin (3j)
Purple crystals; mp >300 ꢀC; yield: 135 mg, 29%; spectroscopic
data are identical to that reported in the literature.24b
NMR (100 MHz, CDCl3): d 117.6, 119.4, 125.7, 125.9, 126.8, 129.8 (br
s), 133.5, 134.5, 139.5, 140.9. MALDI-TOF-MS m/z [MþH]þ calcd for
C44H28Cl2N4: 683.2, found: 683.1.
4.2.8. 5,15-Bis-(4-methoxyphenyl)-10,20-diphenyl-porphyrin (4a)
Purple crystals; mp >300 ꢀC; yield: 74 mg, 22%; Rf 0.80 (CH2Cl2);
4.2.12. 5,15-Bis-(4-bromophenyl)-10,20-diphenyl-porphyrin (4e)
Purple crystals; mp >300 ꢀC; yield: 116 mg, 30%; Rf 0.94
UV–vis lmax (CH2Cl2) (log
647 (3.8); IR (KBr): 3305, 3047, 2924, 2851, 1702, 1596, 1503, 1465,
1345, 1215, 1155, 966, 792, 726, 697 cmꢁ1 1H NMR (400 MHz,
3
): 420 (4.0), 516 (4.4), 552 (4.1), 592 (3.9),
(CH2Cl2); UV–vis lmax (CH2Cl2) (log
590 (3.8), 645 (3.7); IR (KBr): 3440, 2924, 2851, 1633, 1594, 1552,
1472, 1345, 1172, 1068, 1011, 965, 796, 722 cmꢁ1 1H NMR
(400 MHz, CDCl3):
3): 418 (4.6), 514 (4.4), 549 (4.0),
;
;
CDCl3):
d
ꢁ2.73 (br s, 2H, NH), 4.02 (s, 6H, OCH3), 7.21 (d, J¼8.5, 4H),
d
ꢁ2.90 (br s, 2H, NH), 7.61–7.72 (m, 6H), 7.78 (d,
7.64–7.69 (m, 6H), 8.05 (d, J¼8.4, 4H), 8.14 (m, 8H, pyrrole-H); 13C
J¼8.1, 4H), 7.98 (d, J¼8.1, 4H), 8.12 (d, J¼6.4, 4H), 8.73 (d, J¼4.6, 4H,
NMR (100 MHz, CDCl3):
d 117.5, 117.6, 119.4, 121.4, 125.7, 126.8,
pyrrole-H), 8.78 (d, J¼4.6, 4H, pyrrole-H); 13C NMR (100 MHz,
128.9, 129.9 (br s), 133.5, 134.8, 140.0, 140.9. MALDI-TOF-MS m/z
CDCl3): d 117.6, 119.4, 121.4, 125.7, 126.8, 128.9, 129.9 (br s), 133.5,
[MþH]þ calcd for C44H30N4: 675.3, found: 675.0.
134.8, 140.0, 140.9. MALDI-TOF-MS m/z [MþH]þ calcd for
C44H28Br2N4: 771.1, found: 771.9.
4.2.9. 5,15-Bis-(4-methylphenyl)-10,20-diphenyl-porphyrin (4b)
Purple crystals; mp >300 ꢀC; yield: 96 mg, 30%; Rf 0.94 (CH2Cl2);
UV–vis lmax (CH2Cl2) (log 3): 418 (3.5), 515 (4.0), 550 (3.6), 590 (3.4),
4.3. The synthesis of 4-methyl-N-(phenyl(5-(phenyl(1H-
pyrrol-2-yl)methyl)-1H-pyrrol-2-yl)methyl)benzene
sulfonamide (5) and 5,50-(phenylmethylene)bis(2-(phenyl(1H-
pyrrol-2-yl)methyl)-1H-pyrrole) (7)
646 (3.3); IR (KBr): 3321, 3008, 2689, 2605, 1814, 1591, 1558, 1471,
1347, 1214, 1182, 964, 800, 787, 735, 700 cmꢁ1; 1H NMR (400 MHz,
CDCl3):
7.65–7.70 (m, 6H), 8.01 (d, J¼8.1, 4H), 8.12 (d, J¼7.5, 4H), 8.74–8.79
(m, 8H, pyrrole-H); 13C NMR (100 MHz, CDCl3):
21.6, 120.0, 120.3,
d
ꢁ2.66 (br s, 2H, NH), 2.60 (s, 6H, CH3), 7.45 (d, J¼7.6, 4H),
d
N-Benzylidene-4-methylbenzenesulfonamide (0.5 mmol) and
Cu(OTf)2 (0.05 mmol) were dissolved in THF (10 mL) at 0 ꢀC and
5 mL solution of 5-phenyldipyrromethane (1.5 mmol) in THF was
added dropwise after 30 min. The reaction was monitored with TLC
and 5 mL of H2O was added to the reaction mixture when the re-
action completed. The aqueous layer was extracted with 2ꢂ10 mL
of ether. The organic phase was dried over anhydrous MgSO4. The
solvent was then removed under reduced pressure and crude
product was purified by flash column chromatography (1:6 EtOAc/
hexane).
126.7, 127.5, 127.7, 131.1 (br s), 134.6, 137.4, 139.3, 142.3. MALDI-TOF-
MS m/z [MþH]þ calcd for C46H34N4: 643.3, found: 643.2.
4.2.10. 5,15-Bis-(4-nitrophenyl)-10,20-diphenyl-porphyrin (4c)
Purple crystals; mp >300 ꢀC; yield: 63 mg, 18%; Rf 0.83 (CH2Cl2);
UV–vis lmax (CH2Cl2) (log 3): 420 (5.0), 516 (4.2), 551 (3.9), 590 (3.7),
646 (3.6); IR (KBr): 3450, 3316, 2957, 2918, 1594, 1515, 1344, 1261,
1104,1015, 965, 844, 799, 724, 700 cmꢁ1; 1H NMR (400 MHz, CDCl3):
d
ꢁ2.87 (br s, 2H, NH), 7.59–7.72 (m, 6H), 8.14 (d, J¼7.2, 4H), 8.32 (d,
J¼8.2, 4H), 8.57 (d, J¼8.3, 4H), 8.68 (d, J¼4.7, 4H, pyrrole-H), 8.84 (d,
J¼4.6, 4H, pyrrole-H); 13C NMR (100 MHz, CDCl3):
d 116.1,120.9,121.0,
4.3.1. 4-Methyl-N-(phenyl(5-(phenyl(1H-pyrrol-2-yl)methyl)-1H-
pyrrol-2-yl)methyl) benzene sulfonamide (5)
Brown viscous oil; yield: 144 mg, 60%; Rf 0.24 (1:3 EtOAc/hex-
ane); IR (KBr): 3429, 2924, 2845, 1720, 1645, 1488, 1452, 1322, 1281,
1156, 1085, 1023, 808, 769, 699, 666, 561 cmꢁ1; 1H NMR (400 MHz,
123.3,125.8,127.0,129.4,133.5,134.1,140.6,146.8,147.9. MALDI-TOF-
MS m/z [MþH]þ calcd for C44H28N6O4: 705.2, found: 705.1.
4.2.11. 5,15-Bis-(4-chlorophenyl)-10,20-diphenyl-porphyrin (4d)
Purple crystals; mp >300 ꢀC; yield: 92 mg, 27%; Rf 0.94 (CH2Cl2);
CDCl3):
d
2.39 (br s, 3H, CH3), 5.36 (d, J¼6.68, 1H, HNSO2), 5.53–5.58
UV–vis lmax (CH2Cl2) (log
645 (3.6); IR (KBr): 3441, 3310, 3025, 1555, 1470, 1440, 1347, 1092,
1017, 965, 799, 715, 697 cmꢁ1 1H NMR (400 MHz, CDCl3):
3): 415 (3.8), 514 (4.3), 549 (3.9), 589 (3.8),
(m, 3H, 2ꢂCH, pyrrole-H), 5.70 (br s, 1H, pyrrole-H), 5.89 (br s, 1H,
pyrrole-H), 6.13 (br s, 1H, pyrrole-H), 6.64 (br s, 1H, pyrrole-H),
7.12–7.57 (m, 10H, Ar–H), 8.03 (br s, 1H, NH), 8.36 (br s, 1H, NH); 13C
;
d
ꢁ2.90
(br s, 2H, NH), 7.61–7.70 (m, 10H), 8.03 (d, J¼8.1, 4H), 8.12 (d, J¼7.2,
NMR (100 MHz, CDCl3):
d 21.5, 44.0, 55.9, 107.2, 107.3, 108.3, 108.4,
4H), 8.72 (d, J¼4.4, 4H, pyrrole H), 8.77 (d, J¼4.4, 4H, pyrrole-H); 13C
117.3, 126.9, 127.3, 127.7, 128.4, 128.6, 129.5, 130.1, 132.5, 133.8, 137.1,

B. Temelli, C. Unaleroglu / Tetrahedron 65 (2009) 2043–2050
2049
138.8, 142.1, 143.3. Anal. Calcd for C29H27N3O2S: C, 72.32; H, 5.65; N,
8.72; S, 6.66. Found: C, 71.97; H, 5.72; N, 8.53; S, 6.81.
temperature under N2 atmosphere. The solution of compound 6
(0.1 mmol) in 5 mL of dichloromethane was added to the mixture.
DDQ was added to this solution after 1.5 h. Water (5 mL) was added
to the mixture after 2 h and the aqueous phase was extracted with
dichloromethane (3ꢂ10 mL). After removing the solvent under
reduced pressure, the crude product was purified by flash column
chromatography (CH2Cl2).
4.3.2. 5,50-(Phenylmethylene)bis(2-(phenyl(1H-pyrrol-2-
yl)methyl)-1H-pyrrole) (7)
Brown viscous oil; yield: 27 mg, 10%; Rf 0.36 (1:3 EtOAc/hex-
ane); IR (KBr): 3429, 2924, 2857, 1695, 1627, 1488, 1451, 1286, 1158,
1113, 1068, 875, 769, 716, 700 cmꢁ1 1H NMR (400 MHz, CDCl3):
;
d
5.31 (br s, 1H, CH), 5.38 (br s, 2H, CH), 5.73–5.75 (m, 4H, pyrrole-
Acknowledgements
H), 5.88 (br s, 2H, pyrrole-H), 6.16 (br s, 2H, pyrrole-H), 6.69 (br s,
2H, pyrrole-H), 7.17–7.52 (m, 11H, Ar–H), 7.74 (br s, 2H, NH), 7.92 (br
s, 2H, NH), 8.11–8.15 (m, 4H, Ar–H); 13C NMR (100 MHz, CDCl3):
The authors thank Hacettepe University for financial support
(BAP projects 0302601004 and 01G014). The authors would also
like to thank Prof. Dr. B. Salih and O. Celikbicak for MALDI-TOF mass
measurements.
d
44.1, 44.2, 107.3, 107.4, 108.4, 117.2, 126.5, 126.8, 126.9, 128.3, 128.4,
128.5, 128.6, 129.4, 129.7, 130.2, 132.2, 132.3, 132.5, 133.7, 142.1.
4.4. The synthesis of N,N0-(5,50-(phenylmethylene)bis(1H-
pyrrole-5,2-diyl)bis(phenylmethylene))bis(4-
methylbenzenesulfonamide) (6)
References and notes
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2000, 4, 414–417.
N-Benzylidene-4-methylbenzenesulfonamide (1.5 mmol) and
Cu(OTf)2 (0.15 mmol) were dissolved in THF (10 mL) at ꢁ20 ꢀC. A
solution (5 mL) of dipyrromethane (0.5 mmol) in THF was added
dropwise into the reaction mixture after 30 min. The reaction was
monitored with TLC and 5 mL of H2O was added when the reaction
completed. The aqueous layer was extracted with 2ꢂ10 mL of ether.
Combined organic phase was dried over anhydrous MgSO4 and the
solvent was evaporated under reduced pressure. The product was
purified by flash column chromatography (1:4 EtOAc/hexane) and
was obtained as a diastereoisomeric mixture.
4.4.1. N,N0-(5,50-(Phenylmethylene)bis(1H-pyrrole-5,2-
diyl)bis(phenylmethylene))bis(4-methylbenzenesulfonamide) (6)
Brown viscous oil; yield: 252 mg, 68%; Rf 0.23 (1:3 EtOAc/hex-
ane); IR (KBr): 3379, 3269, 2922, 2851, 1598, 1493, 1453, 1426, 1323,
1157, 1092, 1026, 909, 809, 731, 699, 664, 563 cmꢁ1 1H NMR
;
(400 MHz, CDCl3): d 2.24 (s, 6H, CH3), 2.25 (s, 6H, CH3), 5.18 (s, 1H),
5.23 (s, 1H), 5.24 (br s, 1H), 5.31 (br s, 1H), 5.35–5.41 (m, 5H), 5.46–
5.59 (m, 6H), 5.78 (br s, 1H), 6.37 (d, J¼9.6, 1H), 6.44 (d, J¼9.6, 1H),
7.00–7.23 (m, 38H, Ar–H), 7.23–7.50 (m, 8H, Ar–H), 8.25 (br s, 2H,
2ꢂNH), 8.42 (br s, 1H, NH), 8.47 (br s, 1H, NH); 13C NMR (100 MHz,
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d 20.4, 20.5, 43.0, 43.1, 54.9, 55.0, 55.1, 106.2, 106.3, 106.4,
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106.7, 107.2, 107.5, 107.6, 107.7, 125.7, 125.8, 125.9, 126.1, 126.2, 126.3,
126.4, 126.6, 126.7, 126.8, 127.2, 127.3, 127.4, 127.5, 128.3, 128.4,
128.5, 129.0, 129.2, 129.9, 130.3, 132.3, 132.5, 133.3, 135.9, 136.0,
136.2, 136.3, 136.8, 136.9, 137.5, 137.6, 140.6, 140.7, 140.8, 142.2,
142.3,142.4. Anal. Calcd for C43H40N4O4S2: C, 69.70; H, 5.44; N, 7.56;
S, 8.66. Found: C, 69.45; H, 5.47; N, 7.91; S, 8.37.
4.5. The synthesis of 5,10,15,20-tetraphenylporphyrin (3a) via
self-condensation of sulfonamidealkyldipyrromethane 5
Cu(OTf)2 (0.02 mmol) was added to the solution of compound 5
(0.2 mmol) in 20 mL of dichloromethane under N2 atmosphere. The
mixture was stirred for 1.5 h and the solution of 0.3 mmol DDQ in
dichloromethane was added to the reaction mixture. After 2 h,
water (5 mL) was added to the mixture and aqueous phase was
extracted with dichloromethane (3ꢂ10 mL). After removing the
solvent under reduced pressure, the crude product was purified by
flash column chromatography (CH2Cl2).
4.6. The synthesis of 5,10,15,20-tetraphenylporphyrin (3a) via
condensation of bis(sulfonamidealkyl)dipyrromethane 6 with
5-phenyldipyrromethane (1a)
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5-Phenyldipyrromethane (1a) (0.1 mmol) and Cu(OTf)2
(0.01 mmol) were dissolved in 5 mL of dichloromethane at room
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2050
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