Synthesis and self-assembling behavior of a porphyrin bearing multiple meso-conjugated barbiturates

Article abstract of DOI:10.1016/j.tetlet.2010.07.139

An efficient procedure through deprotection of 2,4,6-trimethoxypyrimidine derivative afforded porphyrinato zinc bearing multi-barbiturates acting as multiple hydrogen bonding sites at the meso positions. Addition of excess amphiphilic triaminopyrimidine derivative, as a complementary motif to the barbiturate, in an aqueous solution of porphyrin conjugated with multiple barbiturates at the meso positions resulted in precipitation. The cast film from the chloroform solution of the precipitate indicated the formation of a well-defined porphyrin assembly.

Full text of DOI:10.1016/j.tetlet.2010.07.139

Tetrahedron Letters 51 (2010) 5177–5180
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis and self-assembling behavior of a porphyrin bearing multiple
meso-conjugated barbiturates
Satoshi Arai, Toshiya Okamura, Shinji Takeoka *
Department of Life Science and Medical Bioscience, Faculty of Science and Engineering, Waseda University, TWIns 2-2 Wakamtsu-cho, Shinjuku-ku, Tokyo 162-8480, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient procedure through deprotection of 2,4,6-trimethoxypyrimidine derivative afforded porphyr-
inato zinc bearing multi-barbiturates acting as multiple hydrogen bonding sites at the meso positions.
Addition of excess amphiphilic triaminopyrimidine derivative, as a complementary motif to the barbitu-
rate, in an aqueous solution of porphyrin conjugated with multiple barbiturates at the meso positions
resulted in precipitation. The cast film from the chloroform solution of the precipitate indicated the for-
mation of a well-defined porphyrin assembly.
Received 14 July 2010
Accepted 23 July 2010
Available online 1 August 2010
Keywords:
Porphyrin
Hydrogen bonding
Self-assembly
Barbituric acid
Ó 2010 Elsevier Ltd. All rights reserved.
Recently, self-assembled porphyrins have received considerable
attention because of the wide range of potential applications, such
as the development of efficient catalysts and optical devices. In-
deed, there are successful reports on porphyrin-assemblies via
noncovalent interactions such as electrostatic interactions, hydro-
into meso positions function as direct hydrogen bonding units on
both sides of the porphyrin plane, thereby expanding the structural
dimension of the assembly. Moreover, from a synthetic viewpoint,
the design avoids the need to separate atropisomers.
In order to prepare the targeting porphyrin, 5-formylbarbituric
acid was synthesized according to a previous report (Scheme 1).7
The ring condensation with pyrrole and its formyl derivative was
carried out using the Lindsey and Adler methods, respectively.5
However, the desired meso-arylporphyrin could not be detected.
The failure of this procedure is due, at least in part, to the poor sol-
ubility of the barbiturate derivative in the organic solvent. Addi-
tionally, 5-formylbarbituric acid adopts an enol form as a result
of tautomerization, which might not be tolerated under acidic con-
1
phobic interactions, coordination bonding, and hydrogen bonding.
We have focused on hydrogen bonding as a desirable means of
assembling the molecular components because of their inherent
directionality and selectivity.2 In particular, we are able to
construct on-target porphyrin-assemblies using a well-known
complementary hydrogen bonding system between donor–accep-
,8
3,4
tor–donor (DAD) and acceptor–donor–acceptor (ADA).
In order to design a more sophisticated porphyrin-assembly,
three important factors need to be considered. (i) Multipoint
hydrogen bonding motifs should be incorporated into the porphy-
rin scaffold as a functional core for enthalpic reasons in order to
maintain a stable assembly. (ii) Entropic loss involved in bringing
molecules together into an assembly should be as low as possible.
Indeed, a previous report describes this entropic effect for porphy-
rin-assembly by incorporation of hydrogen bonding motifs at the
9
ditions. Therefore, the synthetic route through deprotection of the
methoxy groups of the pyrimidine was chosen because 2,4,6-tri-
methoxypyrimidine was expected to be converted to barbituric
acid as shown in Scheme 1.
2,4,6-Trimethoxypyrimidine (1) was obtained by the reaction of
2,4,6-trichloropyrimidine with sodium methoxide as a nucleo-
1
0
philic reagent. Following treatment of 1 with n-butyllithium,
the lithio derivative was precipitated. Reaction at À70 °C with
ethylformate as an electrophile then gave 5-formyl-2,4,6-trimeth-
5
meso positions. In this way, unfavorable entropic loss should be
minimized due to an increase in structural rigidity. (iii) Regulation
of atropisomers resulting from the free rotation of carbon–carbon
1
1
oxypyrimidine (2). The ring condensation succeeded at higher
concentrations of aldehyde-pyrrole (50 mM) than that of the Lind-
sey method using general conditions to give a 5,10,15,20-tetrakis-
(2,4,6-trimethoxy-pyrimidin-5-yl)-porphyrin (3) at 55% yield. The
methoxy groups of 3 were easily deprotected by iodotrimethylsi-
lane to generate meso-conjugated barbiturates porphyrin as a free
4
bonds at meso positions enhances the control of self-assembly.
To meet the above requirements a porphyrin bearing four barbitu-
rates at meso positions, which act as multipoint hydrogen bonding
sites, was designed. Indeed, this is, a well-known component of a
2
ADA type molecular assembly.6 Multi-barbiturates incorporated
1
2
base form. After insertion of zinc to the porphyrin by addition of
zinc chloride, purification was performed using Sephadex LH-20 to
give 5,10,15,20-tetrakis-(2,4,6-trioxo-hexahydro-pyrimidin-5-yl)-
*
Corresponding author. Tel./fax: +81 3 5369 7324.
E-mail address: takeoka@waseda.jp (S. Takeoka).
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.07.139

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S. Arai et al. / Tetrahedron Letters 51 (2010) 5177–5180
Scheme 1. Synthesis of meso-conjugated barbiturates porphyrin. Reagents and conditions: (a) KOH, CHCl
3
; (b) NaOMe, toluene at reflux; (c) n-BuLi, Et
at 50 °C.
2
O at À30 °C; (d)
ethylformate, at À70 °C; (e) pyrrole, BF (OEt) at rt, p-chloranil, CH Cl , at reflux; (f) (i) (CH SiI, at 45 °C; (ii) ZnCl
3
2
2
2
)
3 3
2
porphyrinato zinc, that is, meso-conjugated barbiturates porphyri-
nato zinc (ZnBarP) in 90% yield. The infrared spectrum of ZnBarP
(
KBr) gave peaks corresponding to the stretching vibration of the
À1
carbonyl groups at 1698 and 1573 cm , which are in agreement
with those of typical barbituric acid derivatives.13 The N–H-
À1
stretching vibration was also observed around 3200 cm in a sim-
ilar manner to that of barbituric acid.
We obtained absorption spectra of ZnBarP in three different
solvents, that is, DMSO, methanol, and water. From a structural
viewpoint, the hydroxy form of barbituric acid dominates over
the oxo form in an aqueous solution.14 ZnBarP exhibited the high-
er solubility in water (more than 50 mg/ml) than in organic sol-
vents such as methanol (ca. less than 0.1 mg/ml) and DMSO (ca.
less than 1.0 mg/ml) because the hydroxy form existed as a mix-
ture of mono- and dianionic states. As shown in Figure 1, the
UV–vis spectrum of ZnBarP displays an absorption band around
2
50 nm, suggesting that ZnBarP is present as a mixture of mono-
1
4
and dianionic forms of barbituric acid at the meso positions.
Interestingly, the DMSO solution showed the larger red shift of
the Soret band (450 nm) than water (426 nm) and methanol
(
429 nm). It was assumed that the barbiturate moiety would take
an oxo form having the proton at the C5 position of the barbiturate
in DMSO, which might cause steric repulsion with the protons at
pyrrolic b positions resulting in the distortion of the porphyrin
plane.
Figure 1. UV–vis spectra of ZnBarP (10 lM) in methanol, water and DMSO.
In order to investigate the self-assembling property of ZnBarP,
-(2-{2-[2-(2-octyloxy-ethoxy)-ethoxy]-ethoxy}-ethyl)-pyrimidine-
centrifuged to isolate the precipitate. The composition of the pre-
cipitate was then characterized by H NMR in CDCl and UV–vis
3
1
5
2
,4,6-triamine (C8EO4TAP) as a 2DAD type having both hydro-
spectra (see the Supplementary data). Interestingly, the molar ratio
philic and hydrophobic moieties was synthesized as described in
a previous report. When aqueous solutions of ZnBarP (1 mM)
and C8EO4TAP were mixed at different molar ratios (1:1, 1:2,
of ZnBarP/C8EO4TAP was 1:4 even if excess C8EO4TAP was added
to the ZnBarP aqueous solution (Fig. 2).
1
5
16
The interaction of ZnBarP with C8EO4TAP was characterized by
IR spectroscopy using a KBr sample of the precipitate. A peak cor-
responding to vibration of the carbonyl groups appeared at
1
:3, 1:4, and 1:8, respectively), the amount of precipitate gradually
increased as the proportion of C8EO4TAP increased. After the
mixed solution was allowed to stand for 48 h at room temperature,
the amount of precipitate was saturated. The suspension was
À1
1645 cm after complexation of ZnBarP with C8EO4TAP (cf. peak
À1
of the unbound carbonyl group at 1698 cm ). The mechanism of

S. Arai et al. / Tetrahedron Letters 51 (2010) 5177–5180
5179
precipitation would be as follows: units of barbituric acid specifi-
cally interact with triaminopyrimidine units to generate the com-
plex with the hydrophobic parts of C8EO4TAP located toward
the outside. Thus, the precipitate was highly soluble in organic sol-
vents such as chloroform but not in water. Moreover the solution
displayed a high level of viscosity. The UV–vis spectrum of the vis-
cous chloroform solution was determined using a thin cell with a
0
.1 mm pathlength. A slight blue-shift was detected indicating H-
aggregation of a face-to-face type as shown in Figure 3.
This spectrum agreed with the behavior of the hydrogen-
bonded face-to-face dimer as reported previously.4 The peak
half-width of the complex of ZnBarP with C8EO4TAP was broad-
ened in comparison with the isolated state of ZnBarP in water,
suggesting an accumulation of porphyrin at high density. In addi-
tion, the UV–vis spectra of the mixture of ZnBarP and C8EO4TAP
gave the similar Q-band with the monomeric ZnBarP in water,
indicating that the amino and pyrimidinyl groups of C8EO4TAP
should not coordinate to the zinc core of ZnBarP.
We observed a film cast from the viscous chloroform solution of
ZnBarP and C8EO4TAP using a polarized optical microscope (POM)
as shown in Figure 4.
When C8EO4TAP alone was cast from aqueous or chloroform
solutions on a glass plate, no anisotropy was observed. By contrast,
the polarized microscopic image of a mixture of ZnBarP and
C8EO4TAP did show anisotropy that was different from the texture
of the ZnBarP crystal. If the composition ratio of ZnBarP and
C8EO4TAP in the assembly changed during an evaporation process
involved in cast from the chloroform solution onto the glass, the
POM image arising from ZnBarP (crystal) or C8EO4TAP (isotropy)
alone as shown in Figure 4 would be observed in the mixed sample
with ZnBarP and C8EO4TAP. We can conclude that the composi-
tion ratio of the assembly on the solid surface should be 1–4,
reflecting the ratio determined in the solution state as shown in
Figure 2. When the film consists of ZnBarP and C8EO4TAP was
analyzed by X-ray diffraction, the peak of 3 nm ascribed to the
packing of the alkyl chain was observed (see the Supplementary
data). Noncovalent interactions presumably promote the adoption
of a face-to-face arrangement of the porphyrin where the hydro-
phobic alkyl chains are positioned on the outside, resulting in a
highly ordered structure via the packing of the alkyl chain. Future
optimization of the length and flexibility of the chains using
triaminopyrimidine derivatives will improve the stability of the
rod-like structure and facilitate the construction of highly ordered
arrays via chain packing.
Figure 2. Analysis of the precipitation composed of ZnBarP and C8EO4TAP.
In conclusion, we have demonstrated an efficient synthetic
route to a water-soluble porphyrin bearing multi-barbituric acids
(ZnBarP) and discuss the complementary 2DAD type self-assem-
bling possibilities induced by amphiphilic triaminopyrimidine
Figure 3. UV–vis spectra of ZnBarP–C8EO4TAP solution 1 mM using thin cell
0.1 mm).
derivatives. Although some previous reports describe porphyrins
(
bearing heterocyclic compounds at the meso positions,8 this is
Figure 4. Polarlized microscope images of ZnBarP, C8EO4TAP, and ZnBarP–C8EO4TAP on a glass plate.

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S. Arai et al. / Tetrahedron Letters 51 (2010) 5177–5180
the first such report to use barbituric acid. ZnBarP is a promising
candidate for synthetic strategies where introduction of multiple
barbiturate moieties is required for construction of supramolecular
assemblies based on other hydrophobic functional molecules, such
as phthalocyanines or triphenylenes. The film composed of a por-
phyrin assembly, based on the complementary system of barbitu-
rate and triaminopyrimidine, has a dense array of aligned active
sites provided by the central metals of the porphyrin. Such an
assembly can be used in a variety of applications (e.g., catalysts,
membranes or novel functional materials), especially if different
metals are inserted into the porphyrin ring system.
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Supplementary data
Supplementary data (General experimental method, experi-
mental details, and characterization data for compounds 1–3, and
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sion, at doi:10.1016/j.tetlet.2010.07.139.
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