Towards the synthesis of substituted porphyrins by a pyridyl group bearing a reactive functionality

Article abstract of DOI:10.1142/S108842461000232X

Pyridyl-substituted porphyrins bearing a reactive functionality were prepared via Suzuki cross-coupling reactions and resulted in very good yields. These compounds are precursors of new porphyrin architectures able to coordinate two metals: one in the porphyrin core and the second around the pyridyl moiety. During the coupling reactions, a higher reactivity of a chloro picolyl group was evidenced compared to a bromo function on the same reacting molecule.

Full text of DOI:10.1142/S108842461000232X

Journal of Porphyrins and Phthalocyanines
J. Porphyrins Phthalocyanines 2010; 14: 469–480
DOI: 10.1142/S108842461000232X
Published at http://www.worldscinet.com/jpp/
Towards the synthesis of substituted porphyrins by a pyridyl
group bearing a reactive functionality
Maya El Ojaimi, Benoit Habermeyer, Claude P. Gros◊ and Jean-Michel Barbe*◊
ICMUB UMR 5260, Université de Bourgogne, 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France
Received 5 November 2009
Accepted 25 January 2010
ABSTRACT: Pyridyl-substituted porphyrins bearing a reactive functionality were prepared via Suzuki
cross-coupling reactions and resulted in very good yields. These compounds are precursors of new
porphyrin architectures able to coordinate two metals: one in the porphyrin core and the second around
the pyridyl moiety. During the coupling reactions, a higher reactivity of a chloro picolyl group was
evidenced compared to a bromo function on the same reacting molecule.
KEYWORDS: A3B-porphyrins, pyridyl substituted porphyrins, Suzuki coupling, meso-functionalization.
approach for the synthesis of porphyrins bearing from
INTRODUCTION
two to four meso-pyridyl groups [17]. It consists of the
Although porphyrins and their structural variants have
basic condensation of 1-acyldipyrromethanes in the pres-
been extensively studied by organic chemists, less atten-
tion has been devoted during the last decades to the syn-
thesis of unsymmetrical porphyrins functionalized by a
reactive group [1–12]. The lack of effective synthesis for
ence of magnesium bromide. This pathway allows for
easy access to trans-A2B2 and trans-A2-porphyrins [17].
However, mono-meso-pyridyl substituted porphyrins are
still difficult to obtain.
this type of compound may be one of the main reasons.
Here, we show that substituted porphyrins by a pyridyl
On the other hand, there has been an increasing demand
for unsymmetrical substituted porphyrins, i.e. chiral or
amphiphilic porphyrins for various applications in por-
group bearing a reactive functionality (Chart 1) can be
easily prepared in good yields by Suzuki coupling start-
ing from a A3B-porphyrin. The pyridine nucleus is an
phyrin-based biomimetic systems, biological studies,
ubiquitous structural motif in catalysis, supramolecular
catalysis, optics, molecular materials etc. [13–16] and
chemistry, and medicinal chemistry (…) [18–21]. The
despite a high demand, many applications are currently
search for efficient routes toward pyridine-containing
hampered due to their synthetic inaccessibility. Multi-
chiral structures is the key to the development of new
step syntheses are possible for selected types of substitu-
catalysts for a wide range of enantioselective transforma-
ents but still suffer in too many cases from acid-catalyzed
tions. Our goal here is to introduce a reactive group on
scrambling, making them too cumbersome for large-scale
the pyridyl ring in order to further functionalize the mole-
synthesis or industrial use.
In the particular case of meso-pyridyl substituted por-
phyrins, the main problem stems from acid-catalyzed
cule by a ligand allowing coordination of a second metal.
Indeed, it occurs to us that incorporation of one pyridyl
group bearing a reactive functionality at the meso-posi-
protocols which lead to the protonation of the pyridine
tion of the porphyrin macrocycle should offer an efficient
ring by the acid catalyst, thus inducing deactivation of
entry into novel molecular architectures (e.g. new flex-
the catalyst and also precipitation of the pyridinium salt
ible dyads, Scheme 1) by providing a third coordination
[5]. Lindsey and co-workers developed a step-by-step
site. This third metalation site should afford the means
by which the flexibility of the tweezer can be modulated
and should allow, at the same time, for the introduction
SPP full member in good standing
of a new factor to the physical studies (e.g. closing and
opening of the binding pocket).
*Correspondence to: Jean-Michel Barbe, email: Jean-Michel.
Barbe@u-bourgogne.fr, fax: +33 (0)3 80 39 61 17
Copyright © 2010 World Scientific Publishing Company

470
M.E. OJaIMI et al.
X = -CH2-OH, -CH2-Cl, -CHO, -CO2CH3
Mes
N
N
Reactive
functionality
N
X
M
M = Zn, 2H...
Mes
N
N
Mes
1st coordination site
2nd possible
coordination site
precursors to
new flexible
dyads
N
N
N
M1
N
H
N
N
N
N
M2
H
N
N
N
M1
N
3rd coordination site
Chart 1. Substituted porphyrin by a pyridyl group bearing a reactive functionality. Possible access to new flexible dyads allowing
three-metal coordination
CHO
HO
OH
+
+
+
N
N
N
N
N
N
Mes
Mes
H
H
H
H
N
N
H
H
Mes
Mes
H
H
N
N
Pathway #2a
Pathway #1
Pathway #2b
X
X
Mes
N
N
N
X
M
Mes
N
N
M = 2H or M = Zn,...
Mes
Pathway #3
Mes
CHO
CHO
+
Br
+
O
O
N
N
N
B
+
M
Mes
N
N
H
X
N
X
N
Mes
Scheme 1. Different synthetic routes to access the unsymmetrical A3B type porphyrin
porphyrins (e.g. involving pyrrole and two different
aldehydes) would, unfortunately, lead to a mixture of
six isomers (from A4-type to B4-type through A3B, A2B2,
AB3 substitutions, as statistically expected, see pathway
1 in Scheme 1) [22]. Such a mixed condensation reac-
tion often requires laborious and lengthy chromato-
graphic separation that affords only small quantities of
the desired porphyrin. Therefore, this approach was not
further considered.
RESULTS AND DISCUSSION
The structures of the studied functionalized porphy-
rins are described in Chart 2.
Different synthetic routes can be considered in order
to access the unsymmetrical A3B type porphyrins. Four
of them are presented in Scheme 1.
The synthesis of the less symmetric A3B-substituted
porphyrin requires the establishment of two types of
meso-carbon: one bearing the pyridyl substituent and
the other an aryl group (e.g. mesityl). A variation of
the well-known acid-catalyzed synthesis of TPP-like
Two main syntheses are classically used to pre-
pare A3B-porphyrins, involving either an A3-dipyrro-
methanedicarbinol and a B-dipyrromethane, or aA- and a
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 470–480

SynthESIS Of SubStItutED POrPhyrInS by a PyrIDyl grOuP
471
Mes
Mes
N
N
N
N
N
OHC
M
M
Mes
Mes
N
N
N
Cl
N
N
Mes
Mes
8: M = 2H
Zn-8: M = Zn
13: M = 2H
Zn-13: M = Zn
Mes
Mes
N
N
M
N
N
M
MeO2C
OHC
Mes
Mes
N
N
N
N
N
N
Mes
Mes
9: M = 2H
Zn-9: M = Zn
14: M = 2H
Zn-14: M = Zn
Br
Mes
Mes
N
N
N
N
N
N
N
M
Mes
M
Mes
N
N
HO
N
Mes
12: M = 2H
Mes
15: M = 2H
Zn-15: M = Zn
Zn-12: M = Zn
Chart 2. Structures of prepared compounds
B-dipyrromethane with an A-aldehyde (pathways 2a and
2b respectively, Scheme 1). Pathway 2a consists of the
condensation of a dipyrrolic compound carrying the link-
ing carbon in the form of a hydroxymesityl group with
the α-free substituted pyridyldipyrromethane [23]. Path-
way 2b, the acid-catalyzed condensation of two different
dipyrromethanes with mesitylaldehyde, is a variation of
the classical synthesis of 5,15-diphenylporphyrins. Path-
way 2a, when compared to 2b, has the intrinsic disad-
vantage of requiring additional synthetic steps, and the
hydroxymesityl derivatives, prepared generally by reduc-
tion of the parent carbonyl compounds, are known to be
very sensitive. Finally, the synthesis of the pyridyl-sub-
stituted porphyrin can be pursued by a Suzuki coupling
route (involving the preparation of a dioxaborolane-
porphyrin) to avoid the obvious potential complications of
condensation of pyrrole or dipyrromethane with the pyri-
dyl aldehyde derivative [24–33]. However, this synthesis
requires more reaction steps than the previous ones.
Pathways 2a and 2b both start with the preparation of a
pyridyl dipyrromethane bearing a reactive functionality.
This latter is generally synthesized in a one-step proce-
dure from pyrrole [34–37] and, in our case, pyridine alde-
hyde. The key chloromethyl-pyrid-3-yl-carbaldehyde 5
of pathways 2a and 2b was prepared in a four-step proce-
dure starting from the diethyl ester (Scheme 2). The syn-
thetic route to 6-chloromethyl-pyrid-3-yl-carbaldehyde 5
began with reduction of diethyl pyridine-2,5-dicarboxy-
late 1 to ethyl 6-(hydroxy-methyl)-pyrid-3-yl-carboxylate
2 using sodium borohydride in 66% yield. The resulting
hydroxy derivative 2 was further converted to the chloro
by thionyl chloride to give 3 in 76% yield. Reduction of 3
with LiAlH4 finally gave the (6-chloromethyl-pyrid-3-yl)
methanol 4 (in 83% yield), which was further oxidized
to aldehyde 5 in 92% using 2-iodoxybenzoic acid in dry
dimethylsulfoxide at room temperature. The overall yield
for this four-step procedure is more than 38%.
Our first attempts to prepare the (chloromethyl)pyri-
dyldipyrromethane 6′ by a one-flask reaction of the pyri-
dine aldehyde 5 with pyrrole in the absence of any solvent
were unsuccessful (Scheme 2). The general procedure for
the preparation of a dipyrromethane usually requires the
presence of acid catalysts: TFA, HCl or mild Lewis acid
(i.e. BF3·OEt2, InCl3, MgBr2) [34–37]. The synthesis can
also be performed by heating at high temperature in the
absence of any acid but the yield is usually lower [23].
As reported in the literature, acidic medium for het-
erocyclic aldehydes (specially 2-, 3- or 4-pyridine-
carboxylate) is problematic [23]. The pyridylaldehyde 5
was dissolved in excess of pyrrole and heated at 85 °C for
8 h without any catalyst. The resulting dipyrromethane
was then purified by filtration through a pad of silica, fol-
1
lowed by recrystallization. H NMR spectrum showed
the disappearance of a peak at about 4.75 ppm (s, 2H,
-CH2-Cl) and the appearance of a singlet at 5.87 ppm. In
addition, two new doublets at 6.26 and 6.82 ppm corre-
sponding to a N-alkylated pyrrole ring were also observed.
We concluded that the chloro-leaving group has been
removed during the reaction, leading to an N-alkylated
(pyrrolo)pyridyldipyrromethane 6. ESI mass spectrom-
etry confirmed the presence of the N-alkylated pyrrole
(m/z = 303.17 [M + H]+ and m/z = 325.15 [M + Na]+).
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 471–480

472
M.E. OJaIMI et al.
OH
CO2Et
SOCl2
CO2Et
NaBH4
CO2Et
Cl
Cl
HO
LiAlH4
N
N
N
EtO2C
N
4
3
2
1
2-iodoxybenzoic
acid
N
N
H
N
N
H
H
H
CHO
16 h, 85 °C
+
N
N
N
Cl
H
N
6'
6: 38%
5
N
Cl
Mw = 271.74
Scheme 2. Tentative synthesis of a pyridyl dipyrromethane
Mw = 302.37
NH
NH
HN
HN
H
Mes-CHO
2 eq.
Mes
1 eq.
1 eq.
1) BF3·OEt2 (0.6 eq.)
CH2Cl2; 30 min
2) TEA (5 eq.),
DDQ (3 eq.), 1 h
Mes
Mes
Mes
NH
N
NH
N
NH
N
Mes
N
Mes
HN
N
N
Mes
HN
HN
Mes
Mes
Mes
Br
N
by-products
CHCl3, 30 min
O
O
(1 eq.)
O
O
Mes
Mes
Mes
B
H
(8 eq.)
O
B
O
Zn(OAc)2·2H2O (2 eq.)
NH
N
N
N
N
N
N
N
N
Br
Br
Zn
Zn
Mes
Mes
Mes
HN
N
N
CH2Cl2:MeOH (85:15)
NEt3 (3 eq.),
1 h, 85 °C
PdCl2(PPh3)2 (0.03 eq.)
DCE; reflux 90 min
Mes
Mes
Mes
Zn-7
Scheme 3. Synthesis of the dioxaborolane-porphyrin Zn-7
The nucleophilic substitution of the chloro leaving group
by a pyrrole ring clearly evidences the sensitivity of the
ortho-position of the pyridyl group and its instability in
acidic media. This unexpected result led us to focus on
pathway 3 detailed in Scheme 3.
The synthetic pathway leading to the porphyrin pre-
cursor for the Suzuki coupling is shown in Scheme 3.
Following the conditions described by Shultz et al. for
the synthesis of the trimesityl-porphyrin [38], a mixture
of three porphyrins was obtained. The resulting mixture
was then used in the following steps without any purifi-
cation. The bromination was carried out with a standard
method by treatment of the mixture with N-bromosuc-
cinimide (NBS) in chloroform at room temperature for
30 min. The bromo-porphyrins were further metalated
with Zn(OAc)2·2H2O to give the zinc complexes, which
were coupled with pinacolborane under PdCl2(PPh3)2
catalysis to yield a mixture of boronate-porphyrins and
tetramesityl porphyrin. The dioxaborolane-porphyrin 7,
previously described by Nocera et al. [25, 26], was then
easily separated from the others by column chromatogra-
phy affording Zn-7 in 14% overall yield.
The functionalized porphyrin Zn-8 was prepared in
high yields (85%) by a Suzuki coupling reaction of por-
phyrin Zn-7 and 6-bromo-pyridine-3-carbaldehyde using
a catalytic amount of Pd(OAc)2 and anhydrous Cs2CO3
in the presence of PPh3 in a mixture of DMF/toluene at
85 °C for 8 h (Scheme 4) [31–33, 38, 39].
The same experimental conditions were applied for
the preparation of Zn-9, starting from the dioxaborolane-
porphyrin Zn-7 and 5-bromo-pyridine-2-carbaldehyde but
this reaction required heating up to 105 °C for a longer
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 472–480

SynthESIS Of SubStItutED POrPhyrInS by a PyrIDyl grOuP
473
Isomer #1
Mes
Cs2CO3 (1.5 eq.)
Pd(OAc)2 (0.2 eq.)
Mes
O
O
N
N
N
N
N
N
B
OHC
Br +
OHC
OHC
Zn
Zn
Mes
Mes
N
N
PPh3 (0.6 eq.)
DMF/toluene 8 h, 85 °C
N
N
N
Mes
HCl (1M)
Mes
1.1 eq.
1 eq.
Zn-8
85%
Zn-7
Mes
NH
N
N
Mes
HN
Mes
85%
8
Isomer #2
Mes
Cs2CO3 (1.5 eq.)
Pd(OAc)2 (0.2 eq.)
Mes
O
O
N
N
N
N
N
N
B
OHC
Br +
OHC
OHC
Zn
Zn
Mes
Mes
N
N
PPh3 (0.6 eq.)
DMF/toluene 16 h, 105 °C
N
N
N
Mes
Mes
78%
1.1 eq.
1 eq.
HCl (1M)
Zn-9
Zn-7
Mes
NH
N
N
Mes
HN
Mes
88%
9
Scheme 4. Synthetic procedures for porphyrins 8 and 9
time (16 h). In both cases, the coupling reactions were
monitored by TLC and MALDI-TOF mass spectrometry.
The higher reactivity observed during the preparation of
Zn-8 can be explained by the presence of the nitrogen
atom at the ortho-position of the bromo-leaving group in
the starting pyridine-carbaldehyde, which enhances the
reactivity of the bromo group. Demetalation of the zinc
porphyrins Zn-8 and Zn-9 using HCl 1 M at room tem-
perature afforded the free-base derivatives, porphyrins 8
and 9, in yields superior to 85%.
We further tried the reactivity of 5-bromo-2-chlorom-
ethyl-pyridine 11 with porphyrin Zn-7 using the same
Suzuki coupling conditions (Scheme 5). The 5-bromo-2-
chloromethyl-pyridine 11 was synthesized in two
steps by reduction of the aldehyde function of bromo-
picolinaldehyde using LiAlH4 in THF at 0 °C, followed
by nucleophilic substitution of the hydroxy-leaving
group by chloro using thionyl chloride in toluene.
Unexpectedly, after 7 h at 80 °C, the MALDI-TOF
mass spectrum did not exhibit the expected molecular
peak at m/z = 852.84 corresponding to porphyrin Zn-13
but a peak at m/z = 897.10 Daltons (way 2, Scheme 5).
The isotopic distribution confirmed the presence of a
zinc porphyrin bearing a bromine atom instead of the
expected chloride. Based on different assumptions, two
protocols (ways 1 and 2 in Scheme 5) can be considered
to explain the observed MALDI-TOF mass spectrum:
(i) the Suzuki coupling route could have occurred on
the chloro-leaving group rather than the bromo one,
or (ii) the bromine atoms released during the catalytic
reaction could lead to a nucleophilic substitution of the
chloro substituent.
A closer look at the 1H NMR spectrum of the isolated
porphyrin is informative (Fig. 1). The absence of any
singlet in the 4–5 ppm range and the presence of a sin-
glet at 6.59 ppm (2H) are in agreement with the structure
of porphyrin 12. Indeed, for comparison, the methylene
groups of either the 2,6-dibromomethylpyridine or the
5-bromo-2-chloromethylpyridine compounds appear at
δ = 4.70 ppm (s, 2H, -CH2-Br) [40] and δ = 4.63 ppm (s,
2H, -CH2-Cl) [40], respectively, whereas the methylene
groups of tetrabenzylporphyrin appear at δ = 6.34 ppm
(s, 8H, -CH2-Ph) [41]. Therefore, only the formation of
porphyrin 12 occurs in 90% yield using this synthetic
procedure and unfortunately the target porphyrin Zn-13
was present only as traces. It is also worthy to note on the
MALDI-TOF spectrum of the reaction mixture the pres-
ence of a peak at m/z = 1541.48 daltons. This peak can
be attributed to the formation of a dimer (Scheme 6) cor-
responding to the Suzuki coupling of the dioxaborolane-
porphyrin Zn-7 with the zinc bromopyridylporphyrin
Zn-12. This dimer was not further characterized.
Copyright © 2010 World Scientific Publishing Company
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474
M.E. OJaIMI et al.
Br
Br
Br
OHC
N
Mes
N
N
NH
N
N
LiAlH4
Mes
HN
Mes
12
Br
Br
HO
N
N
Mes
10
N
N
N
Zn
Way 2
Mes
SOCl2
N
Mes
Mes
Cs2CO3 (1.5 eq.)
Pd(OAc)2 (0.2 eq.)
85%
Zn-12
Way 1
Way 2
O
O
N
N
N
+
B
Cl
Zn
Mes
N
PPh3 (0.6 eq.)
DMF/toluene 7 h, 100 °C
Way 1
Mes
Mes
11
Zn-7
N
N
1 eq.
1 eq.
N
Zn
Mes
N
Cl
N
N
Mes
Zn-13
CsBr
100 °C
Mes
N
N
N
Zn
Mes
N
Br
Mes
Scheme 5. Porphyrin Zn-7 and Suzuki couplings
Fig. 1. HR-MS and 1H NMR spectra of porphyrin 12
Copyright © 2010 World Scientific Publishing Company
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SynthESIS Of SubStItutED POrPhyrInS by a PyrIDyl grOuP
475
Br
Cs2CO3 (1.5 eq.)
Pd(OAc)2 (0.2 eq.)
PPh3 (0.6 eq.)
Mes
Mes
Mes
N
N
Mes
O
O
N
N
N
N
N
N
Zn
B
N
Zn
Zn
N
N
N
N
+
Mes
N
N
N
N
Zn
DMF/toluene 7 h,
Mes
Mes
N
Mes
100 °C
Mes
Mes
Mes
Mes
Zn-7
Exact Mass: 1541.5667
Zn-12
Scheme 6. Formation of a dimer via Suzuki coupling
Mes
Mes
N
Cs2CO3 (1.5 eq.)
Pd(OAc)2 (0.2 eq.)
O
O
N
N
N
N
B
MeO2C
MeO2C
Br +
Zn
Zn
Mes
Mes
N
N
N
N
N
PPh3 (0.6 eq.)
DMF/toluene 30 h, 100 °C
Mes
Mes
67%
Zn-7
Zn-14
DiBAl-H (3 eq.)
THF, 1 h
Mes
Mes
SOCl2
NH
N
N
N
N
N
Zn
Mes
Mes
HN
N
Cl
toluene
N
HO
N
Mes
Mes
93%
98%
13
Zn-15
1M HCl
CH2Cl2, rt
Mes
NH
N
N
Mes
HN
HO
N
Mes
15
Scheme 7. Three-step procedure for the synthesis of porphyrin 13
This latter result led us to investigate a new three-step
procedure to synthesize porphyrin 13 (Scheme 7). Indeed,
the other possibility to obtain the porphyrin 13 consists
of the introduction of the chloromethyl functionality
after the Suzuki coupling reaction. This was successfully
performed by reacting methyl-5-bromopyridine-2-car-
boxylate with Zn-7 under the same Suzuki reaction con-
ditions as above (Scheme 7). Zn-14 was obtained in 67%
yield. The further reduction of the methyl ester group by
DiBAl-H, followed by chlorination of the alcohol deriva-
tive (Zn-15), led to 13 in quantitative yield.
spectra and accurate mass measurements (HR-MS) were
obtained on a Bruker Daltonics Ultraflex II spectrometer
in the MALDI-TOF reflectron mode using dithranol as
a matrix or on a Bruker micrOTOF-Q instrument in ESI
mode. Accurate mass measurements (HR-MS MALDI-
TOF) were carried out in the same conditions as before
using PEG ion series as internal calibrant. Both measure-
ments were made at PACSMUB. GC-MS analysis were
carried out on a Thermo Trace GC-Ultra-DSQII instru-
ment in EI ionization mode (using a Thermo TR-5MS
non-polar column, 0.25 mm × 30 m length). The melting
points were measured on a Büchi B-545 apparatus and
are uncorrected.
EXPERIMENTAL
Chemicals and reagents
Instrumentation
Absolute dichloromethane (CH2Cl2) was obtained
from Carlo Erba and used as received. Silica gel (Merck;
70–120 mm) and alumina (Merck; aluminum oxide 90
standardized) were used for column chromatography.
Analytical thin-layer chromatography was performed
using Merck 60 F254 silica gel (precoated sheets, 0.2 mm
thick). Reactions were monitored by thin-layer chroma-
tography, UV-visible spectroscopy, and MALDI-TOF
1H NMR and 13C NMR spectra were recorded on a
Bruker Avance 300 spectrometer at the “Plateforme
d’Analyse Chimique et de Synthèse Moléculaire de
l’Université de Bourgogne (PACSMUB)”; chemical
shifts are expressed in ppm relative to chloroform (7.26
ppm for 1H and 77 ppm for 13C). UV-visible spectra were
recorded on a Varian Cary 1 spectrophotometer. Mass
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 475–480

476
M.E. OJaIMI et al.
mass spectrometry. 5-mesityldipyrromethane was syn-
thesized as already described [42]. 6-bromo-pyridine-
3-carbaldehyde, 5-bromo-pyridine-2-carbaldehyde and
methyl-5-bromopyridine-2-carboxylate are commercialy
available and were used as received (Acros and Alfa
Aesar). The pyridyl precursors 1–4 were described in the
literature [43, 44].
Ethyl6-chloromethyl-pyrid-3-yl-carboxylate(3).To
a solution of 2 (43.0 g, 237 mmol, 1 eq.) in toluene
(500 mL) was slowly added thionyl chloride (52 mL,
716 mmol, 3 eq.). The suspension was stirred at room
temperature for 3 h till complete dissolution.After all vol-
atiles were removed under reduced pressure, the residue
was dissolved in CH2Cl2 (100 mL), washed three times
with saturated hydrogen carbonate solution (1000 mL),
and then dried over magnesium sulfate. The compound
was purified through alumina column chromatography
using CH2Cl2 as eluent. The title compound was isolated
in 76% yield (35.7 g, 180 mmol) as a yellow powder; mp
Synthesis
Diethyl pyridine-2,5-dicarboxylate (1). To a suspen-
sion of 2,6-dipicolinic acid (60.0 g, 360 mmol, 1 eq.)
in ethanol (500 mL) was slowly added thionyl chloride
(200 mL, 2.75 mol, 7.6 eq.). The mixture was refluxed
for 14 h. After all volatiles were removed under reduced
pressure, the residue was dissolved in CH2Cl2, washed
three times with saturated hydrogen carbonate solution,
and then dried over magnesium sulfate. The title com-
pound was isolated in almost quantitative yields (98.9%,
79.5 g, 356 mmol) as a slightly yellow solid compound;
mp 46–47 °C. 1H NMR (300 MHz; CDCl3; 298 K): δ, ppm
1
42–43 °C. H NMR (300 MHz; CDCl3; 298 K): δ, ppm
1.40 (t, 3H, 3JH-H = 7.1 Hz, CH2-CH3), 4.41 (q, 2H, 3JH-H
=
7.1 Hz, CH2-CH3), 4.71 (s, 2H, CH2-Cl), 7.56 (d, 1H,
3
3JH-H = 8.1 Hz, Hmeta-pyridine), 8.32 (dd, 1H, JH-H = 8.1
4
4
Hz, JH-H = 1.9 Hz, Hpara-pyridine), 9.15 (d, 1H, JH-H
=
1.9 Hz, Hortho-pyridine). 13C NMR (75 MHz; CDCl3; 298
K): δ, ppm 14.2 (CH2-CH3), 46.1 (CH2-Cl), 61.5 (CH2-
CH3), 122.2 (C5-pyridine), 125.6 (C3-pyridine), 138.2
(C4-pyridine), 150.5 (C2-pyridine), 160.5 (C6-pyridine),
164.9 (CO).
1.45 (t, 3H, 3JH-H = 7.1 Hz, CH2-CH3), 1.48 (t, 3H, 3JH-H
=
7.1 Hz, CH2-CH3), 4.46 (q, 2H, 3JH-H = 7.1 Hz, CH2-CH3),
(6-chloromethyl-pyrid-3-yl)methanol (4). To a solu-
tion of LiAlH4 (204 mg, 5.4 mmol, 0.6 eq.) in dry tetra-
hydrofuran (40 mL) was added at 0 °C a solution of 3
(1.8 g, 9 mmol, 1 eq.) in dry tetrahydrofuran (30 mL).
The mixture was stirred at that temperature for 1 h and
then warmed to room temperature and quenched with
water (5 mL). After evaporation of the solvent in vac-
uum, the residue was extracted with CH2Cl2, washed with
water, dried over magnesium sulfate, and then filtered.
The title compound was isolated in 83% yield (1.37 g,
7.56 mmol) as a yellow powder; mp 59–60 °C. 1H NMR
(300 MHz; CDCl3; 298 K): δ, ppm 2.12 (br. s, 1H, OH),
4.67 (s, 2H, CH2-OH), 4.75 (s, 2H, CH2-Cl), 7.47 (d, 1H,
3JH-H = 8 Hz, Hmeta-pyridine), 7.76 (dd, 1H, 3JH-H = 8 Hz,
4JH-H = 2.2 Hz, Hpara-pyridine), 8.53 (d, 1H, 4JH-H = 2.2 Hz,
Hortho-pyridine). 13C NMR (75 MHz; CDCl3; 298 K): δ,
ppm 46.4 (CH2-Cl), 62.3 (CH2-OH), 122.7 (C5-pyridine),
135.8 (C3-pyridine), 138.7 (C4-pyridine), 148.1 (C2-pyri-
dine), 155.8 (C6-pyridine).
4.52 (q, 2H, 3JH-H = 7.1 Hz, CH2-CH3), 8.21 (dd, 1H, 3JH-H
=
=
8.1 Hz, 5JH-H = 0.8 Hz, Hmeta-pyridine), 8.45 (dd, 1H, 3JH-H
4
8.1 Hz, JH-H = 2.1 Hz, Hpara-pyridine), 9.33 (dd, 1H,
4JH-H = 2.1 Hz, 5JH-H = 0.8 Hz, Hortho-pyridine). 13C NMR
(75 MHz; CDCl3; 298 K): δ, ppm 14.2 (CH2-CH3), 14.3
(CH2-CH3), 61.9 (CH2-CH3), 62.4 (CH2-CH3), 124.6
(C3-pyridine), 128.8 (C5-pyridine), 138.2 (C4-pyridine),
150.8 (C2-pyridine), 151.1 (C6-pyridine), 164.4 (CO),
164.5 (CO). GC-MS (EI, 70 eV): m/z (%) 222.9 (100)
[M]+•, 223.08 calcd. for C11H13NO4.
Ethyl 6-(hydroxy-methyl)-pyrid-3-yl-carboxylate
(2). To a suspension of 1 (80.0 g, 360 mmol, 1 eq.) in
ethanol (1000 mL) was added pellets of sodium boro-
hydride (8.0 g, 210 mmol, 0.6 eq.) and the mixture was
refluxed for 14 h. After all volatiles were removed under
reduced pressure, the residue was dissolved in CH2Cl2,
washed three times with saturated hydrogen carbonate
solution, and then dried over magnesium sulfate. The
compound was purified through alumina column chro-
matography using CH2Cl2/MeOH (50/50) as eluents.
The title derivative was isolated in 66% yield (43.0 g,
6-chloromethyl-pyrid-3-yl-carbaldehyde (5). To a
solution of 4 (1.37 g, 7.56 mmol, 1 eq.) in dry dimethyl-
sulfoxide (20 mL) was added 2-iodoxybenzoic acid
(2.68 g, 9.56 mmol, 1.1 eq.). The mixture was stirred at
room temperature for 2 h, and then quenched with addi-
tion of sodium hydrogen carbonate (0.1 M). After evapo-
ration of the solvent in vacuum, the residue was extracted
with CH2Cl2, dried over magnesium sulfate, and then
filtered. The title compound was isolated in 92% yield
237 mmol) as a yellow powder; mp 50–51 °C. 1H NMR
3
(300 MHz; CDCl3; 298 K): δ, ppm 1.41 (t, 3H, JH-H
=
=
7.1 Hz, CH2-CH3), 2.85 (sl, 1H, OH), 4.41 (q, 2H, 3JH-H
7.1 Hz, CH2-CH3), 4.82 (s, 2H, CH2-OH), 7.39 (d, 1H,
3JH-H = 8.1 Hz, Hmeta-pyridine), 8.29 (dd, 1H, 3JH-H = 8.1
4
4
Hz, JH-H = 2.1 Hz, Hpara-pyridine), 9.14 (d, 1H, JH-H
=
2.1 Hz, Hortho-pyridine). 13C NMR (75 MHz; CDCl3;
298 K): δ, ppm 14.2 (CH2-CH3), 61.9 (CH2-CH3), 64.9
(CH2-OH), 120.0 (C5-pyridine), 124.9 (C3-pyridine),
138.2 (C4-pyridine), 149.9 (C2-pyridine), 163.6 (C6-pyri-
dine), 165.1 (CO). GC-MS (EI, 70 eV): m/z (%) 178.8
(100), 181.07 calcd. for C9H11NO3 (molecular peak not
visible).
(1.36 g, 8.79 mmol) as yellow oil; mp 52–53 °C. H
1
NMR (300 MHz; CDCl3; 298 K): δ, ppm 4.75 (s, 2H,
CH2-Cl), 7.68 (d, 1H, 3JH-H = 8.1 Hz, Hmeta-pyridine), 8.22
3
4
(dd, 1H, JH-H = 8.1 Hz, JH-H = 2.0 Hz, Hpara-pyridine),
9.03 (d, 1H, 4JH-H = 2.0 Hz, Hortho-pyridine), 10.12 (s, 1H,
CHO). 13C NMR (75 MHz; CDCl3; 298 K): δ, ppm 46.0
(CH2-Cl), 123.7 (C5-pyridine), 130.5 (C3-pyridine), 135.9
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 476–480

SynthESIS Of SubStItutED POrPhyrInS by a PyrIDyl grOuP
477
(C4-pyridine), 150.2 (C2-pyridine), 160.3 (C6-pyridine),
189.9 (CHO).
(250 mL) and triethylamine (3.64 mL) was added. The
mixture was treated with 4,4,5,5-tetramethyl-1,2,3-diox-
aborolane (2.45 mL) in the presence of trans-dichloro-
bis(triphenylphosphine)palladium(II) (42 mg). After 1 h
at 85 °C, the mixture was cooled to room temperature and
the reaction was quenched with aqueous solution of KCl
(30%). The mixture was then washed three times with
water, dried over magnesium sulfate, and then the sol-
vent was evaporated under reduced pressure. The residue
obtained was chromatographed using CH2Cl2/heptane
(first 50/50, then 70/30, and finally 90/10). Chromatogra-
phy afforded mainly two products: the fast-moving zinc
tetra-mesitylporphyrin and the slow-moving title com-
pound. The second red band was collected, affording after
evaporation of the solvent under reduced pressure 1.11
g of the title compound Zn-7 (1.31 mmol, 14% yield);
mp > 300 °C. 1H NMR (300 MHz; CDCl3; 298 K): δ, ppm
1.81 (s, 12H, CH3-pinacol), 1.85 (s, 18H, CH3-mesityl),
2.64 (s, 9H, CH3-mesityl), 7.27 (s, 6H, Hmeta-mesityl),
{[(2-methyl)-pyrrol-1-yl]-pyrid-5-yl}-2,2′-dipyrryl-
methane (6). Under nitrogen and shielding from light,
aldehyde 5 (1.69 g, 10.9 mmol) was mixed with pyr-
role (20 mL), and the mixture was heated at 85 °C for
16 h. After cooling to room temperature and filtration,
the excess pyrrole was evaporated in vacuo with slight
heating on a rotary evaporator to yield a dark oil. The oil
was taken up in minimal dichloromethane, washed three
times with an aqueous solution of NaHCO3 (100 mL),
dried over magnesium sulfate, and then evaporated. The
oil was dried overnight in vacuo at 55 °C to give the title
1
compound in 38% yield (1.25 g, 4.14 mmol). H NMR
(300 MHz; CDCl3; 298 K): δ, ppm 5.45 (s, 1H, CH-
pyridine), 5.87 (m, 2H, H-dipyrromethane), 6.02 (s, 2H,
CH2-pyrrole), 6.15 (m, 2H, H-dipyrromethane), 6.26 (2d,
3
2H, JH-H = 4.3 Hz, H-pyrrole), 6.71 (m, 2H, H-dipyr-
3
romethane), 6.82 (2d, 2H, JH-H = 4.3 Hz, H-pyrrole),
7.12 (d, 1H, 3JH-H = 8.0 Hz, Hmeta-pyridine), 7.42 (dd, 1H,
8.68 (d, 2H, JH-H = 4.6 Hz, Hβ-porphyrin), 8.71 (d, 2H,
3
4
3JH-H = 8.0 Hz, JH-H = 2.3 Hz, Hpara-pyridine), 8.03 (sl,
3JH-H = 4.6 Hz, Hβ-porphyrin), 8.88 (d, 2H, 3JH-H = 4.7 Hz,
Hβ-porphyrin), 9.81 (d, 2H, 3JH-H = 4.7 Hz, Hβ-porphyrin).
UV-vis (CH2Cl2): λmax, nm (ε × 10-3 M-1.cm-1) 419 (453),
550 (13), 594 (2). MS (MALDI-TOF): m/z 852.32 [M]+•,
852.35 calcd. for C53H53BN4O2Zn. HR-MS (ESI): m/z
853.3600 [M + H]+, 853.3631 calcd. for C53H54BN4O2Zn,
875.3430 [M + Na]+, 875.3451 calcd. for C53H53BN4-
NaO2Zn (in agreement with literature data [25, 26]).
5-(5-formylpyrid-2-yl)-10,15,20-trimesitylpor-
phinato-Zn(II) Zn-(8). Under argon and shielding from
light, borolanyl porphyrin 7 (160 mg, 0.187 mmol, 1 eq.),
6-bromopyridine-3-carbaldehyde (38.1 mg, 0.206 mmol,
1.1 eq.) and Cs2CO3 (106.6 mg, 0.28 mmol, 1.5 eq.) were
dissolved in a mixture of anhydrous DMF (12 mL) and
distilled toluene (21 mL). Pd(OAc)2 (8.4 mg, 0.037 mmol,
0.2 eq.). P(Ph)3 (29.3 mg, 0.11 mmol, 0.6 eq.) were
then added and the mixture was heated at 85 °C for 8 h.
After cooling the mixture to room temperature, dichlo-
romethane (150 mL) was added. The mixture was washed
three times with NaHCO3, dried over magnesium sulfate,
and concentrated. The residue obtained was chromato-
graphed on silica (CH2Cl2/MeOH first 100/0 then 98/2).
The red-pink fraction was isolated and the solvent was
removed under reduced pressure to give the title com-
pound in 85% yield (132.2 mg, 0.159 mmol); mp >
300 °C. UV-vis (CH2Cl2): λmax, nm (log ε) 425 (5.42),
555 (4.11), 600 (3.48). HR-MS (MALDI-TOF): m/z
831.2951 [M]+•, 831.2916 calcd. for C53H45N5OZn.
4
2H, NH-dipyrromethane), 8.40 (d, 2H, JH-H = 2.3 Hz,
Hortho-pyridine). GC-MS (EI, 70 eV): m/z (%) 302.4 (48)
[M]+•, 302.15 calcd. for C19H18N4, 236.3 (29) [M - CH2-
pyrrole]+ 145.1 (100) [M - (pyridine-CH2-pyrrole)]+,
302.15 calcd. for C19H18N4. HR-MS (ESI): m/z 303.1717
[M + H]+, 303.1610 calcd. for C19H19N4, 325.1606 [M +
Na]+, 325.1429 calcd. for C19H18N4Na.
5,10,15-trimesityl-20-(4′,4′,5′,5′-tetramethyl-
[1′,3′,2′]dioxaborolan-2′-yl)-porphyrinatoZn(II)(Zn-7).
Under nitrogen and shielding from light, the meso-
unsubstituted dipyrromethane (1.33 g, 9 mmol, 1 eq.),
mesityldipyrromethane (2.38 g, 9 mmol, 1 eq.) and mesi-
tylaldehyde (2.67 g, 18 mmol, 2 eq.) were dissolved in
dichloromethane (1800 mL). After 5 min, BF3·OEt2 (0.66
µL, 5.4 mmol, 0.6 eq.) was added and the mixture was
stirred at room temperature for 30 min. Triethylamine
(6.3 mL, 45 mmol, 5 eq.) and 2,3-dichloro-5,6-dicyano-
1,4-benzoquinone, (DDQ, 6.13 g, 27 mmol, 3 eq.) were
then added under stirring. After 1 h, the reaction mix-
ture was concentrated, filtered over a pad of silica using
dichloromethane as eluent, and then evaporated under
reduced pressure. Following a general procedure, the
residue was redissolved in chloroform (1000 mL) and
an excess of N-bromosuccinimide (NBS, 386 mg) was
added to the mixture. The mixture was stirred at room
temperature for 30 min, concentrated and then filtered
over a pad of silica using dichloromethane as eluent.
A solution of the mixture of brominated and tetramesi-
tyl porphyrins in chloroform/MeOH was treated with
Zn(OAc)2·2H2O (1.5 g) and the mixture was heated at
75 °C. The reaction was monitored by TLC, UV-visible
and MALDI-TOF mass spectrometry. After 2 h, CH2Cl2
was added and the mixture was washed three times with
water (300 mL), one time with NaHCO3, and then dried
over magnesium sulfate. The zinc porphyrins are finally
dissolved under argon in anhydrous 1,2-dichloroethane
5-(5-formylpyrid-2-yl)-10,15,20-trimesitylpor-
phyrin (8). Shielding from light, a solution of the zinc
porphyrin Zn-8 (113.87 mg, 0.137 mmol) in dichlo-
romethane (40 mL) was stirred vigorously with a 1 M
HCl solution (40 mL). After separation of the two phases,
the organic layer was washed two more times with HCl
1 M, then washed three times with water (3 × 50 mL),
dried over magnesium sulfate, filtered and evaporated.
The residue was purified by chromatography (silica,
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 477–480

478
M.E. OJaIMI et al.
dichloromethane/MeOH 98/2). The red fraction was col-
lected and then evaporated to give the title compound in
85% yield (89.5 mg, 0.116 mmol); mp > 300 °C. 1H NMR
(300 MHz; CDCl3; 298 K): δ, ppm -2.49 (br. s, 2H, NH),
1.91 (s, 18H, CH3-mesityl), 2.67 (s, 9H, CH3-mesityl),
7.33 (s, 6H, Hmeta-mesityl), 8.05 (s, 1H, Hmeta-pyridine),
8.46 (s, 1H, Hpara-pyridine), 8.73 (s, 4H, Hβ-porphyrin),
8.82 (s, 4H, Hβ-porphyrin), 9.67 (s, 1H, Hortho-pyridine),
10.51 (s, 1H, aldehyde). UV-vis (CH2Cl2): λmax, nm (log
ε) 419 (5.34), 514 (3.84), 552 (3.84), 591 (3.84), 648
(3.70). MS (MALDI-TOF): m/z 770.34 [M + H]+, 769.38
calcd. for C53H47N5O. HR-MS (ESI): m/z 770.3858
[M + H]+, 770.3859 calcd. for C53H48N5O, 792.3679 [M +
Na]+, 792.3678 calcd. for C53H47N5NaO.
5-(6-formylpyrid-3-yl)-10,15,20-trimesitylpor-
phinato-Zn(II) Zn-(9). Porphyrin Zn-9 was prepared in
78% (485 mg, 0.582 mmol) as a purple compound using
the procedure described above for Zn-8, starting from
5-bromopyridine-2-carbaldehyde (138 mg, 0.755 mmol,
1.1 eq.), Cs2CO3 (424 mg, 1.12 mmol, 1.5 eq.), Pd(OAc)2
(33.4 mg, 0.149 mmol, 0.2 eq.) and P(Ph)3 (116.8 mg,
0.447 mmol, 0.6 eq.), the reaction mixture was heated
5-bromo-2-chloromethyl-pyridine (11). This com-
pound, isolated as a liquid at room temperature, was pre-
pared in 94% (890 mg, 4.34 mmol) using the procedure
described for 3, starting from 10 (864 mg, 4.62 mmol, 1
eq.) and thionyl chloride (1.0 mL, 13.86 mmol, 3 eq.).
1H NMR (300 MHz; CDCl3; 298 K): δ, ppm 4.63 (s, 2H,
CH2-Cl), 7.38 (d, 1H, 3JH-H = 8.3 Hz, Hmeta-pyridine), 7.85
(dd, 1H, 3JH-H = 8.3 Hz, 4JH-H = 2.4 Hz, Hpara-pyridine), 8.63
(d, 1H, 4JH-H = 2.4 Hz, Hortho-pyridine). 13C NMR (75 MHz;
CDCl3; 298 K): δ, ppm 45.9 (CH2-Cl), 120.1 (C5-pyridine),
124.1 (C3-pyridine), 139.7 (C4-pyridine), 150.5 (C6-pyri-
dine), 155.2 (C2-pyridine). GC-MS (EI, 70eV): m/z (%)
204.9 (38) [M]+•, 204.93 calcd. for C6H5BrClN, 169.9.0
(60) [M - Cl]+, 169.96 calcd. for C6H5BrN.
5-(5-bromo-picol-2-yl)-10,15,20-trimesitylporph-
inato-Zn(II) Zn-(12). Porphyrin Zn-12 was prepared
in 78% (284 mg, 0.317 mmol) as a purple compound
using the procedure described for Zn-8, starting from
5-bromo-2-chloromethyl-pyridine 11 (86 mg, 0.42 mmol,
1 eq.), Cs2CO3 (239.5 mg, 0.63 mmol, 1.5 eq.), Pd(OAc)2
(18.9 mg, 0.0084 mmol, 0.2 eq) and P(Ph)3 (65.84 mg,
0.252 mmol, 0.6 eq.), the reaction mixture being heated
at 105 °C for 16 h. mp > 300 °C. UV-vis (CH2Cl2): λmax
,
at 80 °C for 7 h. mp > 300 °C. UV-vis (CH2Cl2): λmax,
nm (log ε) 426 (5.39), 555 (4.08), 601 (3.40). HR-MS
(MALDI-TOF): m/z 831.2897 [M]+•, 831.2916 calcd. for
C53H45N5OZn.
nm (log ε) 422 (5.35), 552 (4.04), 589 (3.40). HR-MS
(MALDI-TOF): m/z 895.2176 [M]+•, 895.2228 calcd. for
C53H46BrN5Zn.
5-(6-formylpyrid-3-yl)-10,15,20-trimesitylporphy-
rin (9). Porphyrin 9 was prepared in 88% (394.19 mg,
0.512 mmol) as a purple compound using the procedure
described above for 8, starting from porphyrin Zn-9 (485
5-(5-bromo-picol-2-yl)-10,15,20-trimesitylporphy-
rin (12). Porphyrin 12 was prepared in 90% (238 mg,
0.285 mmol) as a purple compound using the procedure
described for 8, starting from porphyrin Zn-12 (284 mg,
0.317 mmol). mp > 300 °C. 1H NMR (300 MHz; CDCl3;
298 K): δ, ppm -2.44 (br. s, 2H, NH), 1.88 (s, 18H, CH3-
mesityl), 2.66 (s, 9H, CH3-mesityl), 6.59 (s, 2H, CH2-
1
mg, 0.582 mmol). mp > 300 °C. H NMR (300 MHz;
CDCl3; 298 K): δ, ppm -2.52 (br. s, 2H, NH), 1.87 (s,
18H, CH3-mesityl), 2.64 (s, 9H, CH3-mesityl), 7.31 (s,
3
5
3
6H, Hmeta-mesityl), 8.43 (dd, 1H, JH-H = 7.9 Hz, JH-H
pyridine), 6.64 (d, 1H, JH-H = 8.5 Hz, Hmeta-pyridine),
3
3
= 0.8 Hz, Hmeta-pyridine), 8.69 (d, 6H, JH-H = 4.8 Hz,
7.31 (s, 6H, Hmeta-mesityl), 8.65 (d, 4H, JH-H = 4.9 Hz,
Hβ-porphyrin), 8.72 (dd, 1H, 3JH-H = 7.9 Hz, 4JH-H = 2.0 Hz,
Hpara-pyridine), 8.78 (d, 2H, 3JH-H = 4.8 Hz, Hβ-porphyrin),
Hβ-porphyrin), 8.70 (dd, 1H, 3JH-H = 8.5 Hz, 4JH-H = 2.4 Hz,
Hpara-pyridine), 8.78 (d, 2H, 3JH-H = 4.9 Hz, Hβ-porphyrin),
8.82 (d, 1H, 4JH-H = 2.4 Hz, Hortho-pyridine), 9.42 (d, 2H,
3JH-H = 4.9 Hz, Hβ-porphyrin). UV-vis (CH2Cl2): λmax, nm
(log ε) 418 (5.37), 516 (4.08), 549 (3.70), 593 (3.40), 650
(3.40). MS (MALDI-TOF): m/z 834.31 [M + H]+, 833.31
calcd. for C53H48BrN5. HR-MS (ESI): m/z 834.3166 [M +
H]+, 834.3171 calcd. for C53H49BrN5.
4
5
9.64 (dd, 1H, JH-H = 2.0 Hz, JH-H = 0.8 Hz, Hortho-pyri-
dine), 10.48 (s, 1H, aldehyde). UV-vis (CH2Cl2): λmax, nm
(log ε) 420 (5.32), 516 (3.95), 551 (3.30), 592 (3), 648
(3). MS (MALDI-TOF): m/z 770.41 [M + H]+, 769.38
calcd. for C53H47N5O. HR-MS (ESI): m/z 770.3927 [M +
H]+, 770.3859 calcd. for C53H48N5O.
(5-bromo-pyrid-2-yl)methanol (10). This compound
was prepared in 86% (864 mg, 4.62 mmol) using the pro-
cedure described for 4, starting from 5-bromopicolinal-
dehyde (1.00 g, 5.37 mmol, 1 eq.) and LiAlH4 (122 mg,
3.22 mmol, 0.6 eq.). mp 59–60 °C. 1H NMR (300 MHz;
CDCl3; 298 K): δ, ppm 4.72 (br. s, 1H, OH), 5.22 (s, 2H,
CH2-OH), 7.18 (d, 1H, 3JH-H = 8.3 Hz, Hmeta-pyridine), 7.81
(dd, 1H, 3JH-H = 8.3 Hz, 4JH-H = 2.3 Hz, Hpara-pyridine), 8.63
(d, 1H, 4JH-H = 2.3 Hz, Hortho-pyridine). 13C NMR (75 MHz;
CDCl3; 298 K): δ, ppm 63.9 (CH2-OH), 121.7 (C5-pyri-
dine), 128.8 (C3-pyridine), 139.3 (C4-pyridine), 149.7
(C6-pyridine), 151.1 (C2-pyridine). GC-MS (EI, 70eV):
m/z (%) 187.0 (9) [M]+•, 186.96 calcd. for C6H6BrNO,
156.0 (15) [M - CH2OH]+, 155.94 calcd. for C5H3BrN.
5-(6-methylcarboxylate-pyrid-3-yl)-10,15,20-tri-
mesitylporphinato-Zn(II) (Zn-14). Porphyrin Zn-14
was prepared in 67% (202 mg, 0.235 mmol) as a pur-
ple compound using the procedure described for Zn-8,
starting from methyl-5-bromopyridine-2-carboxylate (82
mg, 0.38 mmol, 1.1 eq.), Cs2CO3 (119 mg, 0.525 mmol,
1.5 eq.), Pd(OAc)2 (15.7 mg, 0.007 mmol, 0.2 eq.) and
P(Ph)3 (54.8 mg, 0.21 mmol, 0.6 eq.), the reaction mix-
ture being heated at 100 °C for 30 h. mp > 300 °C. UV-
vis (CH2Cl2): λmax, nm (log ε) 422 (5.37), 553 (4.04), 593
(3.48). MS (MALDI-TOF): m/z 862.29 [M + H]+, 861.30
calcd. for C54H47N5O2Zn. HR-MS (ESI): m/z 861.2992
[M]+•, 861.3021 calcd. for C54H47N5O2Zn, 884.2884
[M + Na]+, 884.2919 calcd. for C54H47N5NaO2Zn.
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 478–480

SynthESIS Of SubStItutED POrPhyrInS by a PyrIDyl grOuP
479
5-(6-hydroxymethyl-pyrid-3-yl)-10,15,20-trimesi-
HR-MS (ESI): m/z 790.3619 [M + H]+, 790.3676 calcd.
for C53H49ClN5, 812.3422 [M + Na]+, 812.3496 calcd. for
C53H48ClN5Na, 828.3174 [M + K]+, 828.3235 calcd. for
C53H48ClKN5.
tylporphinato-Zn(II) (Zn-15). Under nitrogen and
shielding from light, a solution of porphyrin Zn-14 (200
mg, 0.23 mmol, 1 eq.) in dry THF (25 mL) was treated
with DiBAl-H (0.69 mL, 0.69 mmol, 3 eq.). After 1 h at
room temperature (TLC analysis showed that the reaction
was complete), the reaction was quenched with water (5
mL). The mixture was concentrated to dryness. The resi-
due was dissolved in dichloromethane and washed with
NaHCO3 and then dried over magnesium sulfate. The
residue obtained was chromatographed (silica, dichlo-
romethane/MeOH 100/0 first, then 90/10), affording
the title compound in 98% yield as a purple solid (188
CONCLUSION
The desired porphyrins were obtained without statis-
tical reactions and the approach described here should
prove to be useful for the preparation of a broad vari-
ety of substituted porphyrins by a pyridyl group bearing
different reactive functionalities. The functionalization
of the pyridyl moiety by reactive groups allows for the
preparation of new porphyrin ligands able to coordi-
nate two metals in close proximity. Further work in this
direction and towards more sophisticated structures (e.g.
new flexible dyads allowing three-metal coordination) is
under investigation by our group and will be published in
a forthcoming paper.
mg, 0.225 mmol); mp > 300 °C. UV-vis (CH2Cl2): λmax
,
nm (log ε) 422 (5.46), 552 (4.11). MS (MALDI-TOF):
m/z 834.29 [M + H]+, 834.31 calcd. for C53H47N5OZn.
HR-MS (ESI): m/z 834.3088 [M + H]+, 834.3150 calcd.
for C53H48N5OZn, 856.2922 [M + Na]+, 856.2970 calcd.
for C53H47N5NaOZn.
5-(6-hydroxymethyl-pyrid-3-yl)-10,15,20-trimesi-
tylporphyrin (15). Porphyrin 15 was prepared in 75%
(130 mg, 0.168 mmol) as a purple compound using the
procedure described for 8, starting from porphyrin Zn-15
(188 mg, 0.225 mmol). mp > 300 °C. H NMR (300
MHz; CDCl3; 298 K): δ, ppm -2.54 (br. s, 2H, NH), 1.87
(s, 18H, CH3-mesityl), 2.65 (s, 9H, CH3-mesityl), 4.41
Acknowledgements
The Centre National de la Recherche Scientifique
(ICMUB, UMR CNRS 5260) and the Burgundy Council
are gratefully thanked for financial support. The French
Ministry of Research (MENRT) is acknowledged for
scholarships (M. E.).
1
(br. s, 1H, OH), 5.10 (s, 2H, CH2-OH), 7.31 (s, 6H, Hmeta
-
3
mesityl), 8.51 (d, 1H, JH-H = 8.0 Hz, Hmeta-pyridine),
8.68 (d, 4H, 3JH-H = 4.9 Hz, Hβ-porphyrin), 8.74 (m, 5H,
Hβ-porphyrin + Hpara-pyridine), 9.30 (s, 1H, Hortho-pyri-
dine). UV-vis (CH2Cl2): λmax, nm (log ε) 419 (5.57), 515
(4.20), 550 (3.78), 594 (3.70), 647 (3.48). MS (MALDI-
TOF): m/z 772.36 [M + H]+, 771.40 calcd. for C53H49N5O.
HR-MS (ESI): m/z 772.4010 [M + H]+, 772.4015 calcd.
for C53H50N5O, 794.3779 [M + Na]+, 794.3835 calcd. for
C53H49N5NaO.
REFERENCES
1. Rao PD, Dhanalekshmi S, Littler BJ and Lindsey
JS. J. Org. Chem. 2000; 65: 7323–7344.
2. Feng XD and Senge MO. J. Chem. Soc. Perkin
Trans. 1 2001: 1030–1038.
3. Brinas RP and Bruckner C. Tetrahedron 2002; 58:
4375–4381.
4. Shi BL and Boyle RW. J. Chem. Soc. Perkin Trans.
1 2002: 1397–1400.
5. Gryko DT and Tasior M. Tetrahedron Lett. 2003;
44: 3317–3321.
6. Hatscher S and Senge MO. Tetrahedron Lett. 2003;
44: 157–160.
7. Shi BL, Scobie M and Boyle RW. Tetrahedron Lett.
2003; 44: 5083–5086.
8. Carcel CM, Laha JK, Loewe RS, Thamyongkit P,
Schweikart K-H, Misra V, Bocian DF and Lindsey
JS. J. Org. Chem. 2004; 69: 6739–6750.
9. Ryppa C, Senge MO, Hatscher SS, Kleinpeter E,
Wacker P, Schilde U and Wiehe A. Chem. Eur. J.
2005; 11: 3427–3442.
10. Senge MO. Acc. Chem. res. 2005; 38: 733–743.
11. Zaidi SHH, Fico FM and Lindsey JS. Org. Process.
Res. Dev. 2006; 10: 118–134.
5-(6-chloromethyl-pyrid-3-yl)-10,15,20-trimes-
itylporphyrin (13). Shielding from light, a solution of
porphyrin 15 (125 mg, 0.15 mmol, 1 eq.) in toluene (15
mL) was reacted with thionyl chloride (0.4 mL). The
reaction was monitored by TLC. After 2 h at room tem-
perature, the reaction mixture was concentrated. The
residue was dissolved in dichloromethane, washed three
times with aqueous NaHCO3, and then dried over mag-
nesium sulfate. The crude product was chromatographed
(silica, dichloromethane) to give the title compound as
a purple powder in 93% yield (110 mg, 0.139 mmol);
1
mp > 300 °C. H NMR (300 MHz; CDCl3; 298 K): δ,
ppm -2.52 (br. s, 2H, NH), 1.89 (s, 18H, CH3-mesityl),
2.65 (s, 9H, CH3-mesityl), 5.09 (s, 2H, CH2-Cl), 7.32 (s,
6H, Hmeta-mesityl), 7.94 (d, 1H, 3JH-H = 8.1 Hz, Hmeta-pyri-
3
dine), 8.57 (d, 1H, JH-H = 8.1 Hz, Hpara-pyridine), 8.58
3
3
(d, 4H, JH-H = 4.9 Hz, Hβ-porphyrin), 8.76 (d, 4H, JH-H
= 4.9 Hz, Hβ-porphyrin), 9.44 (s, 1H, Hortho-pyridine).
UV-vis (CH2Cl2): λmax, nm (log ε) 418 (5.58), 515 (4.20),
548 (3.78), 591 (3.70), 646 (3.48). MS (MALDI-TOF):
m/z 790.34 [M + H]+, 790.3676 calcd. for C53H49ClN5.
12. Dahms K, Senge MO and Bakri Bakar M. Eur. J.
Org. Chem. 2007: 3833–3848.
13. Chambron J-C, HeitzV and Sauvage J-P. In The Por-
phyrin Handbook, Vol. 6, Kadish KM, Smith KM
Copyright © 2010 World Scientific Publishing Company
J. Porphyrins Phthalocyanines 2010; 14: 479–480

480
M.E. OJaIMI et al.
and Guilard R. (Eds.) Academic Press: New York,
2000; pp 1–42.
29. Miyaura N,Yanagi T and SuzukiA. Synth. Commun.
1981; 11: 513–519.
14. Chou J-H, Kosal ME, Nalwa HS, Rakow NA and
Suslick KS. In The Porphyrin Handbook, Vol. 6,
Kadish KM, Smith KM and Guilard R. (Eds.)
Academic Press: New York, 2000; pp 44–131.
15. Ogoshi H, Mizutani T, Hayashi T and Kuroda Y.
In The Porphyrin Handbook, Vol. 6, Kadish KM,
Smith KM and Guilard R. (Eds.) Academic Press:
New York, 2000; pp 280–340.
16. Smith KM. In The Porphyrin Handbook, Vol. 1,
Kadish KM, Smith KM and Guilard R. (Eds.)
Academic Press: New York, 2000; pp 1–43.
17. Dogutan DK, Ptaszek M and Lindsey JS. J. Org.
Chem. 2008; 73: 6187–6201.
30. Tremblay-Morin J-P, Ali H and Van Lier JE.
Tetrahedron Lett. 2006; 47: 3043–3046.
31. Peng X, Komatsu N, Kimura T and Osuka A. J. Am.
Chem. Soc. 2007; 129: 15947–15953.
32. Yamaguchi S, Katoh T, Shinokubo H and Osuka A.
J. Am. Chem. Soc. 2007; 129: 6392–6393.
33. Yamaguchi S, Katoh T, Shinokubo H and Osuka A.
J. Am. Chem. Soc. 2008; 130: 14440–14441.
34. Laha JK, Dhanalekshmi S, Taniguchi M, Ambroise
A and Lindsey JS. Org. Process Res. Dev. 2003; 7:
799–812.
35. Lee C-H and Lindsey JS. Tetrahedron 1994; 50:
11427–11440.
18. Chelucci G and Thummel RP. Chem. Rev. 2002;
102: 3129–3170.
19. Cragg PA. A practical guide to supramolecular
chemistry; Wiley & Sons: New York, NJ, 2005
20. Laird T. Org. Process Res. Dev. 2006; 10: 851–852
and references therein.
21. Steed JW and Atwood JL. Supramolecular Chemis-
try, Wiley & Sons: New York, NJ, 2000.
22. Adler AD, Longo FR, Finarelli JD, Goldmacher J,
Assour J and Korsakoff L. J. Org. Chem. 1967; 32:
476.
36. Littler BJ, Miller MA, Hung C-H, Wagner RW,
O’Shea DF, Boyle PD and Lindsey JS. J. Org.
Chem. 1999; 64: 1391–1396.
37. Rohand T, Dolusic E, Ngo TH, Maes W and Dehaen
W. ARKIVOC 2007: 307–324.
38. Shultz DA, Gwaltney KP and Lee H. J. Org. Chem.
1998; 63: 769–774.
39. Sazanovich IV, Balakumar A, Muthukumaran
K, Hindin E, Kirmaier C, Diers JR, Lindsey JS,
Bocian DF and Holten D. Inorg. Chem. 2003; 42:
6616–6628.
23. Gryko D and Lindsey JS. J. Org. Chem. 2000; 65:
2249–2252.
24. Aratani N and Osuka A. Org. Lett. 2001; 3:
4213–4216.
25. Chang CJ, Chng LL and Nocera DG. J. Am. Chem.
Soc. 2003; 125: 1866–1876.
26. Chng LL, Chang CJ and Nocera DG. J. Org. Chem.
2003; 68: 4075–4078.
40. Del Rio I, Gossage RA, Hannu MS, Lutz M, Spek
AL and Van Koten G. Can. J. Chem. 2000; 78:
1620–1626.
41. Lindsey JS, Prathapan S, Johnson TE and Wagner
RW. Tetrahedron 1994; 50: 8941–8968.
42. Brückner C, Posakony JJ, Johnson CK, Boyle RW,
James BR and Dolphin D. J. Porphyrins Phthalo-
cyanines 1998; 2: 455–465.
27. Hata H, Shinokubo H and Osuka A. J. Am. Chem.
Soc. 2005; 127: 8264–8265.
28. Hyslop AG, Kellett MA, Iovine PM and Therien
MJ. J. Am. Chem. Soc. 1998; 120: 12676–12677.
43. Bisel P, Gies J-P, Schlewer G and Wermuth CG.
Biooorg. Med. Chem. Lett. 1996; 6: 3025–3028.
44. N’Goka V, Stenbol TB, Krogsgaard-Larsen P and
Schlever G. Eur. J. Med. Chem. 2004; 39: 889–895.
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