Strapped porphyrin rosettes based on the melamine-cyanuric acid motif. Self-assembly and supramolecular recognition

Article abstract of DOI:10.1016/j.tet.2004.07.072

This paper describes studies on the synthesis, self-assembly behavior, and complexing properties of several strapped porphyrin-incorporated melamine-cyanuric or melamine-barbiturate-based rosette supramolecules in chloroform-d. Strapped porpyrin cyanuric acid H₂1 and its Zn (II) complex Zn1 were designed and synthesized. Both H₂1 and Zn1 could combine melamine derivatives 11 or 12 to afford porphyrin rosettes, which are more stable than the model rosette initially reported by Whitesides due to the larger size of the porphyrin unit. The new porphyrin rosettes could efficiently complex tripyridyl derivative 13 through intermolecular, cooperative coordination between Zn (II) and pyridine. Two new pyridine-bearing barbiturates 18a and 18b were also synthesized. Mixing the identical amount of 18a or 18b with 11 or 12 in chloroform-d led to the formation of new isomeric rosettes as a result of different orientation of the pyridine unit of 18a or 18b in the rosettes. ¹H NMR study also revealed that porpyrin-bearing rosette Zn1₃·11₃ could complex pyridine-bearing rosette 11₃·18a₃, leading to the formation of new two-layer-typed supramolecular architectures.

Full text of DOI:10.1016/j.tet.2004.07.072

Tetrahedron 60 (2004) 9155–9162
Strapped porphyrin rosettes based on the melamine–cyanuric
acid motif. Self-assembly and supramolecular recognition
*
Xue-Bin Shao, Xi-Kui Jiang, Shi-Zheng Zhu and Zhan-Ting Li
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China
Received 27 May 2004; revised 16 July 2004; accepted 23 July 2004
Available online 27 August 2004
Abstract—This paper describes studies on the synthesis, self-assembly behavior, and complexing properties of several strapped porphyrin-
incorporated melamine–cyanuric or melamine-barbiturate-based rosette supramolecules in chloroform-d. Strapped porpyrin cyanuric acid
H21 and its Zn (II) complex Zn1 were designed and synthesized. Both H21 and Zn1 could combine melamine derivatives 11 or 12 to afford
porphyrin rosettes, which are more stable than the model rosette initially reported by Whitesides due to the larger size of the porphyrin unit.
The new porphyrin rosettes could efficiently complex tripyridyl derivative 13 through intermolecular, cooperative coordination between Zn
(II) and pyridine. Two new pyridine-bearing barbiturates 18a and 18b were also synthesized. Mixing the identical amount of 18a or 18b with
11 or 12 in chloroform-d led to the formation of new isomeric rosettes as a result of different orientation of the pyridine unit of 18a or 18b in
the rosettes. 1H NMR study also revealed that porpyrin-bearing rosette Zn13$113 could complex pyridine-bearing rosette 113$18a3, leading
to the formation of new two-layer-typed supramolecular architectures.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
The additional aliphatic strap, which connects two oppo-
sitely located phenyl groups, not only completely prevents
the atropisomerization of the corresponding porphyrins,28,29
but also ensures that any ligand can approach the porphyrin
metal ion only from the strap-free side, and consequently
can improves the selectivity of multi-component recog-
nition.30 In search for new generation of multi-component
porphyrin receptors, we had introduced a cyanuric acid
moiety to the strapped porphyrin skeleton. In this paper, we
report the self-assembly of a new series of hydrogen bonded
rosettes based on this strapped porphyrin-connected cyan-
uric acid and its recognition for tripyridyl and rosette guests.
In recent years, the self-assembly of small molecular units
into larger, ordered architectures has been intensively
investigated for the design of artificial receptors and novel
materials.1–16 Because of its unique feature of directionality,
specificity, and stability, hydrogen bonding has been one of
the most versatile non-covalent forces for the self-assembly
of well-defined supramolecular systems.17–21 Over the
years, a number of efficient triple and quadruple hydrogen
bonding modes have been developed.17–19 The triply
hydrogen bonded melamine–cyanuric acid motif has been
extensively studied for the formation of the so-called
‘rosette’ supramolecuar structures.22 Especially, a number
of elegant double rosettes have been assembled based on
calix[4]arene scaffolds bearing two melamine moieties.23 In
principle, introduction of additional binding or recognizing
units into this relatively stable and highly symmetric
supramolecular architectures might produce new generation
of artificial multi-component receptors or assemblies of
higher order. However, examples of this kind of rosette
receptors are very limited.24–26
2. Results and discussion
Compounds H21 and Zn1 have been used for the self-
assembly of the new porphyrin rosettes. The syntheses of
H21 and Zn1 are provided in Scheme 1. Thus, compound 2
was first treated with excessive dibromide 3 in hot DMF in
the presence of potassium carbonate to produce 4 in 65%
yield. Bromide 4 then reacted with phenol 5 under similar
conditions to afford compound 6 in 72% yield. A Mitsunobu
reaction of 6 with cyanuric acid in DMF gave precursor 7 in
36% yield. Compound 9 was then prepared in 90% yield
from the reaction of 8 and iso-pentyl bromide under the
conditions for preparation of 4. Treatment of 9 with pyrrole
in refluxing toluene under the catalysis of tosyl acid
produced 10 in 76% yield. Dipyrrole 10 was then reacted
with 7 in trifluoroacetic acid, followed by oxidation with
We have recently developed an efficient method to
synthesize strapped tetraphenylporphyrin derivatives.27
Keywords: Hydrogen bonding; Molecular recognition; Self-assembly;
Porphyrin; Heterocyclic compounds.
* Corresponding author. Tel.: C86-21-64163300; fax: C86-21-64166128;
e-mail: ztli@mail.sioc.ac.cn
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.07.072

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X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
14.79 ppm, respectively, for the H-1 of H21 (Fig. 1, the
numbering of the signals are shown in Fig. 2), clearly
showing that rosette structures (H21)3$113 and (H21)3$123
(Fig. 2), were generated.31,32 It had been reported that
melamines with substituents of smaller size, like 12, and
simple alkylated cyanuric acids could only generate infinite
tapes but not cyclic rosette motif.31 The formation of rosette
(H21)3$123 might be ascribed to the introduction of the large
porphyrin unit in H21, which prevents the formation of tape
structures due to enlarged steric hindrance.
Figure 1. Partial 1H NMR spectrum (400 MHz) in chloroform-d at 25 8C:
(a) H21 (10 mM), (b) H21C11 (1:1, 10 mM), (c) H21C11 (1:1, 1 mM), and
(d) H21C12 (1:1, 10 mM).
Scheme 1.
p-chloranil, to produce 1 in 15% yield. Treatment of
porphyrin 1 with zinc acetate in mixture of chloroform and
methanol afford Zn1 quantitatively. Compounds H21 and
Zn1 are highly soluble in common organic solvents such as
chloroform and dichloromethane. With porphyrins H21 and
Zn1 in hand, melamine derivatives 11 and 12 were prepared
according to the reported method.31
Figure 2. Porphyrin rosettes (H21)3$113 (RZt-Bu) and (H21)3$123 (RZn-
Bu) formed in chloroform-d.
Upon reducing the concentration to 1.0 mM, the signals of
the H-1 and H-2 of the 1:1 mixture of H21 with 11 or 12 in
chloroform-d showed very small upfield shifts
(%0.031 ppm) (Fig. 3), indicating that the rosette structures
were stable within the concentration range studied. Previous
study by Whitesides et al. had shown that the model rosette
motif formed from 11 and alkylated cyanuric acid became
unstable at the concentration of less than 4.0 mM in
chloroform.31 The present dilution experiments revealed
that the new rosettes assembled from H21 and 11 or 12 are
Although both 11 and 12 are insoluble in chloroform,
adding 1 equiv of 1 to the suspension of 11 or 12 in
chloroform-d led to the melamines to dissolve completely.
1H NMR spectrum displayed a singlet at dZ14.86 and

X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
9157
and ca. K1.3 ppm for the a-H, b-H, and CH2,
respectively) (Fig. 4). These results clearly indicated
that the supramolecular complex (Zn13$113)$13 was
formed.33 The signals of 13 in the mixture solution had
been assigned by changing the ratio of 13 and the
rosette. The H-1 and H-2 signals of the rosette was also
shifted upfield slightly upon complexation with 13.
Reducing the concentration of the 1:1 mixture of
(Zn1)3$113 with 13 in chloroform-d from 10 to
0.8 mM did not cause notable change of the chemical
shifts of the signals of 13, indicating that no important
dissociation occurred. Attempt to quantitatively study
the binding stability of tri-component complex
[(Zn1)3$113]$13 with the UV–vis titration method did
not succeed since such titration needs the concentra-
tion of the porphyrin receptor to be on the scale of
ca. 10K5–10-6 M. At such low concentration, rosette
Zn13$113 would dissociate partially and could not be
treated as a single species. As expected, similar
supramolecular complex (Zn13$123)$13 was also
formed when the identical molar amount of rosette
(Zn13$113) and 13 was mixed in chloroform-d, which
Figure 3. Concentration-dependent changes of the chemical shifts of H-1
(C) and H-2 (;) of rosette (H21)3$113 and H-1 (&) and H-2 (:) of
rosette (H21)3$123 in chloroform-d at 25 8C.
obviously more stable than the model systems and
indicated that the large porphyrin moiety in H21
facilitated the formation of the rosette motif. 1H NMR
experiments revealed that similar rosettes (Zn1)3$113
and (Zn1)3$123 were also formed when the identical
amount of Zn1 and 11 or 12 were mixed in chloroform-
d. The H-1 signals of both rosettes moved upfield
slightly (K0.040 and K0.058 ppm) compared with the
corresponding Zn (II)-free rosettes. Lowering the
concentration of the 1:1 mixtures in chloroform-d to
1.0 ppm did not cause the H-1 signal to shift
pronouncedly (%K0.033 ppm). The results showed
that these two rosettes are also very stable and there
is no important coordination between the zinc ion of
Zn1 and the amino groups of 11 or 12.
1
had also been supported by the H NMR results.
Figure 4. Partial 1H NMR spectrum (400 MHz) of: (a) 13 (3.3 mM), (b) 13
(3.3 mM)C(Zn1)3$113 (3.3 mM) and (c) (Zn1)3$113 (3.3 mM) in chloro-
form-d at 25 8C.
The binding between different rosettes were also
investigated. Initially, we tried to prepare mono-(4-
pyridyl)methylated cyanuric acid as our precursor to
assemble pyridine-bearing rosette guest. Unfortunately,
the product was insoluble in chloroform even in the
presence of 11 or 12. We then prepared compounds 18a
and 18b as our assembling building blocks, as shown in
Scheme 3.
The complexation of rosette (Zn1)3$113 towards 13 was
then investigated in chloroform-d. Compound 13 was
prepared in 73% yield from 14 and cyanuric acid, as
shown in Scheme 2. Addition of 1 equiv of 13 to the
solution of rosette (Zn1)3$113 in chloroform-d caused
the purplish red color of the rosette solution to change
1
to dark purple. H NMR spectrum revealed remarkable
upfield shifts for all the signals of 13 (K6.73, K1.96,
Scheme 2.
Scheme 3.

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Figure 5. 1H NMR spectrum (400 MHz) in chloroform-d at 25 8C. (a)
113$18a3 (1:1, 3.4 mM), (b) (Zn13$113) (1.7 mM)C113$18a3 (1:1,
3.4 mM), (c) (Zn13$113) (3.4 mM)C113$18a3 (1:1, 3.4 mM), and (d)
(Zn13$113) (3.4 mM).
1H NMR spectrum in chloroform-d revealed that rosette
113$18a3 was also formed when the identical molar
amount of 11 and 18a was mixed (Fig. 5a). In principle,
there were two possible isomers depending on the
relative orientation of 18a in the rosette structure. The
fact that the NH of 18a displayed a broadened signal
1
indicates that the two isomers exchange slowly on the H
NMR time scale. Similar results were also observed
when mixing 11 with 18b or 12 with 18a or 18b in
chloroform-d, suggesting that isomeric rosettes were also
formed in these mixtures. Mixing a solution of 113$18a3
with a solution of Zn13$113 caused the NH signals of
both supramolecules to split into three sets of signals
of comparable integrated strength in the 1H NMR
spectrum in chloroform-d (Fig. 5b and c). The prunosus
color of the solution of rosette (Zn1)3$113 also turned to
dark purple after addition of 113$18a3. These results
clearly indicated that the two rosettes bound each
other to afford the new supramolecular complex
[(Zn1)3$113]$[113$18a3]. The splitting in the 1H NMR
spectrum can be attributed to different orientation of 18a
in the two-layer supramolecular complex. In principle,
there were at most four isomeric complexes formed
between the rosettes because the pyridine units of the
three 18a molecules could have four different patterns
of arrangement in the supramolecular complex: all-up,
up–up–down, up–down–down, and all-down. Unfortu-
nately, at the present stage, we could establish the
relative yields of the isomers. Similar result was also
obtained when rosettes 113$18b3 and Zn13$113 was
mixed, which afforded three sets of signals of the
hydrogen bonded NHs. This observation indicated that
the larger 3,5-di-tert-butylphenyl group did not function
to improve the selectivity of the self-assembly of
supramolecular complex [113$18b3]$[Zn13$113]. The
fact that stable complex [113$18b3]$[Zn13$113] could
be formed between two giant rosette assemblies indicates
that the complexation is a dynamic process and both
assemblies can adapt their conformation to produce a
supramolecular complex as stable as possible.
In principle, introducing pyridine unit to melamine might
lead to its corresponding rosette with Zn1 to be more stable
as a result of additional intermolecular coordination. To
detect this possibility, compound 19 was prepared from the
reaction of compound 20 and 21, followed by treatment of
the intermediates with ammonia gas and 4-pycolyl amine,
consecutively, as shown in Scheme 4. As expected, mixing
the identical molar amount of Zn1 and 19 in chloroform-d
1
generated rosette (Zn1)3$193, as indicated by the H NMR
spectrum (Fig. 6), which displayed the characteristic
hydrogen bonded NH signals in the downfield area. Due
to the unsymmetrical feature of the melamine skeleton, the
1H NMR spectrum displayed multiple sets of signals for the
hydrogen bonded NH of the rosette. This result indicated
that the rosette, in which the three 19 molecules were
arranged completely in one-direction pattern, was not
generated exclusively, although such an arrangement should
facilitate the formation of three intermolecular coordi-
nations between the Zn (II) of Zn1 and the pyridine of 19
and in principle the corresponding rosette should be more
stable than other rosette isomers.34,35

X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
9159
chloroform-d forced 11 to release from the rosette,
obviously due to the formation of more stable complexes
between Zn1 and 19. The release of 11 as insoluble solid
was completed when 1 equiv of 19 was added, as evidenced
by the 1H NMR spectrum (Fig. 6c), which was actually very
close to that of the 1:1 mixture of Zn1 and 19 (Fig. 6d) of the
identical concentration. This observation showed that
rosette (Zn1)3$193 was remarkably more stable than
(Zn1)3$113 as a result of the additional inter-component
coordination in the former assembly.
Scheme 4.
3. Conclusion
We have demonstrated that, by introducing additional
strapped porphyrin unit to the cyanuric acid moiety, the
hydrogen bonded melamine–cyanuric acid-motif-based
rosette assemblies could be utilized as new generation of
supramolecular receptors for binding relatively larger
Adding 19 to the solution of rosette (Zn1)3$113 in
Figure 6. Partial 1H NMR spectrum (400 MHz) in chloroform-d at 25 8C: (a) Zn13$113 (1:1, 3.3 mM), (b) Zn1 (10 mM)C11 (10 mM)C19 (5 mM), (c) Zn1
(10 mM)C11 (10 mM)C19 (10 mM), and (d) Zn13$193 (3.3 mM).

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X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
molecular or supramolecular guests. Although the binding
selectivity needs to be improved further, the interaction
between two discrete rosettes represents a new approach to
the construction of new two-layer-typed supramolecular
architectures. The next step will be introducing two
cyanuric acid units to the opposite phenyl groups of the
porphyrin moiety, which would produce new building block
for assembling two-layer-typed porphyrin boxes for new
molecular or supramolecular encapsulation.
Anal. Calcd for C23H28O8: C, 63.88; H, 6.53. Found: C,
64.07; H, 6.57.
4.1.3.
2-[2-(2-{2-[2-(2-Formyl-phenoxy)-ethoxy]-
ethoxy}-ethoxy)-ethoxy]-5-(2,4,6-trioxo-[1,3,5]triazinan-
1-ylmethyl)-benzaldehyde (7). To a stirred solution of 6
(2.16 g, 5.00 mmol), triphenylphosphine (1.97 g, 7.50 mmol),
and cyanuric acid (1.94 g, 15.0 mmol) in DMF (80 mL) was
added dropwise a solution of DEAD (1.5 equiv, 40% in
toluene) in DMF (10 mL) at room temperature. The solution
was stirred for 60 h and the solvent was evaporated in
vacuo. The resulting residue was washed with water
thoroughly and dried to give a crude product, which was
purified by column chromatography (CH2Cl2/EtOAc/
MeOH, 3:3:0.3) to afford 7 as a white solid (1.02 g, 36%).
1H NMR (400 MHz, CDCl3): d 3.67–3.73 (m, 8H), 3.89 (t,
JZ4.5 Hz, 4H), 4.20 (q, JZ4.7 Hz, 4H), 4.80 (s, 2H), 6.85–
6.99 (m, 3H), 7.49–7.55 (m, 2H), 7.77–7.83 (m, 2H), 9.69
(br, 2H), 10.38 (s, 1H), 10.46 (s, 1H). MS (EI): m/z 427
[MKC3H4N2O3]C. Anal. Calcd for C26H29N3O10: C, 57.45;
H, 5.38; N, 7.73. Found: C, 57.29; H, 5.21; N, 7.52.
4. Experimental
4.1. General methods
1
The H NMR spectra were recorded on 400 or 300 MHz
spectrometers in the indicated solvents. Chemical shifts are
expressed in parts per million (d) using residual solvent
protons as internal standards. Chloroform (d 7.26 ppm) was
used as an internal standard for chloroform-d. Elemental
analysis was carried out at the SIOC Analytical Center.
Unless otherwise indicated, all commercially available
materials were used as received. All solvents were dried
before use following standard procedures. All reactions
were carried out under an atmosphere of nitrogen.
4.1.4. 4-Formyl-benzoic acid 3-methyl-butyl ester (9).
This compound was synthesized in 90% yield as colorless
oil by using the procedure described for preparation of
compound 4. 1H NMR (300 MHz, CDCl3): d 0.99 (d, d, J1Z
1.8 Hz, J2Z6.1 Hz, 6H), 1.66–1.86 (m, 3H), 4.40 (t, JZ
6.6 Hz, 2H), 7.96 (d, JZ7.8 Hz, 2H), 8.20 (d, JZ7.8 Hz,
2H), 10.11 (s, 1H). MS (EI): m/z 220 [M]C. Anal. Calcd for
C13H16O3: C, 70.89; H, 7.32. Found: C, 70.92; H, 7.51.
4.1.1. 2-(2-[2-[2-(2-Bromeothoxy)-ethoxy]-ethoxy]-
ethoxy)-benzaldehyde (4). To a mixture of salicaldehyde
2 (8.50 mL, 80.0 mmol) and potassium carbonate (20.0 g,
0.15 mol) in DMF (100 mL) was added dibromide 3 (60.0 g,
0.19 mol). The mixture was stirred at 100 8C for 5 h and
then concentrated under reduced pressure. The resulting
residue was triturated with ether (500 mL) and the organic
layer washed with diluted sodium hydroxide solution, water,
brine, and dried over sodium sulfate. After evaporation of
the solution in vacuo, the crude product was purified by
column chromatography (petroleum ether/EtOAc, 2.5:1) to
afford the title compound as colorless oil (18.8 g, 65%). 1H
NMR (300 MHz, CDCl3): d 3.47 (5, JZ6.3 Hz, 2H), 3.68–
3.76 (m, 8H), 3.81 (t, JZ6.3 Hz, 2H), 3.93 (t, JZ5.0 Hz,
2H), 4.26 (t, JZ4.7 Hz, 2H), 6.89–7.06 (m, 2H), 7.54 (d, d,
J1Z1.8 Hz, J2Z8.0 Hz, 1H), 7.84 (d, d, J1Z1.8 Hz, J2Z
7.7 Hz, 1H), 10.49 (s, 1H). MS (EI): m/z 281 [MKBr]C.
Anal. Calcd for C15H21Bro5: C, 49.88; Br, 22.12; H, 5.86.
Found: C, 49.71; Br, 22.29; H, 5.86.
4.1.5. 4-[Bis-(1H-pyrrol-2-yl)-methyl]-benzoic acid 3-
methyl-butyl ester (10). A solution of 9 (14.1 g, 64.0 mmol)
and pyrrole (43.0 g, 0.64 mol) in toluene (250 mL) was
degassed by a stream of nitrogen for 30 min. Then, hot
saturated tosyl acid solution in toluene (1 mL) was added in
one portion. The solution was heated under reflux for 1.5 h
and then cooled to room temperature. The solution was
washed with potassium carbonate solution (2 N, 50 mL),
water (50 mL), brine (50 mL), and dried over potassium
carbonate. After the solvent was evaporated under reduced
pressure, the resulting oily residue was purified by column
chromatography (chloroform) to afford compound 10 as a
1
white solid (16.5 g, 76%). H NMR (400 MHz, CDCl3): d
0.97 (d, JZ6.6 Hz, 6H), 1.64–1.83 (m, 3H), 4.34 (t, JZ
6.5 Hz, 3H), 5.52 (s, 1H), 5.89 (s, 2H), 6.16 (q, JZ3.0 Hz,
2H), 6.71 (s, 2H), 7.28 (d, JZ8.1 Hz, 2H), 7.97 (d, JZ
8.1 Hz, 4H). MS (EI): m/z 336 [M]C. Anal. Calcd for
C21H24N2O2: C, 74.97; H, 7.19; N, 8.33. Found: C, 74.76;
H, 7.32; N, 8.08.
4.1.2. 2-[2-(2-[2-[2-(2-Formyl-phenoxy)-ethoxy]-ethoxy]-
ethoxy)-ethoxy]-5-hydroxymethyl-benzaldehyde (6). A
mixture of 3 (7.60 g, 50.0 mmol), 4 (15.6 g, 43.4 mmol),
potassium carbonate (13.0 g, 94.0 mmol) and tetrabutylam-
monium iodide (0.74 g, 2.00 mmol) in DMF (100 mL) was
stirred at 80 8C for 4 h. The solvent was removed under
reduced pressure and the resulting residue was triturated
with dichloromethane (300 mL). The organic phase was
washed with diluted sodium hydroxide solution, water,
brine, and dried over sodium sulfate. After evaporation
under reduced pressure, the residue was subjected to column
chromatography (CH2Cl2/EtOAc, 80:1) to afford 6 as oily
solid (13.6 g, 72). 1H NMR (300 MHz, CDCl3): d 3.68–3.75
(m, 8H), 3.91–3.94 (m, 4H), 4.23–4.27 (m, 4H), 4.65 (s,
2H), 6.97–7.05 (m, 3H), 7.51–7.59 (m, 2H), 7.79–7.84 (m,
2H), 10.49 (s, 1H), 10.50 (s, 1H). MS (EI): m/z 432 [M]C.
4.1.6. Porphyrin H21. Compounds 7 (2.17 g, 4.00 mmol)
and 10 (2.69 g, 8.00 mmol) were dissolved in dichloro-
methane (850 mL). The solution was degassed with nitrogen
for 30 min and then trifluoroacetic acid (1 mL) was added in
one portion. The solution was stirred at room temperature
for 12 h and a solution of 4-chloranil (2.00 g) in THF
(50 mL) was added. The mixture was stirred at room
temperature for another 2 h and then concentrated in vacuo
to afford a solid residue, which was purified by column
chromatography (CH2Cl2/AcOEt/MeOH, 15:10:1). The
desired compound was obtained as a purple solid (0.68 g,
1
15%). Mp 182–182.5 8C. H NMR (400 MHz, CDCl3): d

X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
9161
K2.79 (s, 2H), K0.47- K0.42 (m, 4H), 0.78–0.83 (m, 4H),
1.05 (d, JZ6.3 Hz, 12H), 1.80 (q, JZ6.7 Hz, 4H), 1.88–
1.97 (m, 2H), 2.73–2.79 (m, 2H), 3.71 (t, JZ3.5 Hz, 2H),
3.78 (t, JZ3.5 Hz, 2H), 4.53 (t, JZ6.7 Hz, 4H), 4.95 (s,
2H), 6.99 (d, JZ8.0 Hz, 1H), 7.18 (d, JZ7.5 Hz, 1H), 7.45
(t, JZ7.5 Hz, 1H), 7.64 (d, d J1Z8.0 Hz, J2Z1.5 Hz, 1H),
7.73 (d, d, J1Z8.0 Hz, J2Z1.5 Hz, 1H), 8.19–8.47 (m,
12H), 8.73–8.93 (m, 8H). MS (ESI): m/z 1174 [MCH2O]C.
Anal. Calcd for C68H67N7O12$H2O: C, 68.50; H, 5.84; N,
8.23. Found: C, 68.67; H, 5.84; N, 8.05.
washed with water, brine, and dried over sodium sulfate.
After evaporation of the solvent and column chromato-
graphy (CH2Cl2/EtOAc, 15:1), the crude product 17a was
obtained as oil (3.71 g, 35%). To a solution of sodium
ethoxide (3.40 g, 50.0 mmol) in ethanol (50 mL) was added
urea (0.63 g, 10.5 mmol). Then, the above 17a was added
one portion. The reaction mixture was heated under reflux
for 12 h and then concentrated in vacuo. The resulting
residue was subjected to column chromatography (CH2Cl2/
MeOH, 15:1) to give a crude product. After recrystallization
from ethanol, pure 18a was obtained as a white solid
(1.03 g, 33%). Mp 244–246 8C. 1H NMR (400 MHz,
DMSO-d6): d 0.83 (d, JZ6.5 Hz, 6H), 0.96–1.03 (m, 2H),
1.44–1.48 (m, 1H), 1.94–1.20 (m, 2H), 3.14 (s, 2H), 6.70 (d,
JZ5.4 Hz, 2H), 8.47 (d, JZ5.4 Hz, 2H), 11.50 (s, 1H). MS
(EI): m/z 289 [M]C. Anal. Calcd for C15H19N3O3: C, 62.27;
H, 6.62; N, 14.52. Found: C, 62.20; H, 6.54; N, 14.56.
4.1.7. Porphyrin Zn1. This compound was prepared
quantitatively form H21 after stirring with zinc acetate
(2 equiv) in chloroform and THF at room temperature for
12 h. Mp O200 8C. 1H NMR (400 MHz, CDCl3): d K0.47
to K0.42 (m, 4H), 0.78–0.83 (m, 4H), 1.05 (d, JZ6.3 Hz,
12H), 1.80 (q, JZ6.7 Hz, 4H), 1.88–1.97 (m, 2H), 2.73–
2.79 (m, 2H), 3.71 (t, JZ3.5 Hz, 2H), 3.78 (t, JZ3.5 Hz,
2H), 4.53 (t, JZ6.7 Hz, 4H), 4.95 (s, 2H), 6.99 (d, JZ
8.0 Hz, 1H), 7.18 (d, JZ7.5 Hz, 1H), 7.44 (t, JZ7.5 Hz,
1H), 7.64 (d, d, J1Z8.0 Hz, J2Z1.5 Hz, 1H), 7.73 (d, d,
J1Z8.0 Hz, J2Z1.5 Hz, 1H), 8.19–8.47 (m, 12H), 8.73–
8.93 (m, 8H). MS (ESI): m/z 1237 [MCH]C. Anal. Calcd
for C68H65N7O12Zn: C, 65.99;, 5.29; N, 7.92. Found: C,
65.69; H, 5.14; N, 7.81.
4.1.10. 5-(3,5-Di-tert-butyl-benzyl)-5-pyridin-4-ylmethyl-
pyrimidine-2,4,6-trione (18b). This compound was pre-
pared as a white solid following the procedures described
for 18a. Mp 266 8C. 1H NMR (400 MHz, DMSO-d6): d 1.22
(s, 9H), 3.27–3.33 (m, 4H), 6.86 (d, JZ1.8 Hz, 2H), 7.03 (d,
JZ5.9 Hz, 2H), 7.23 (s, 1H), 8.47 (d, JZ5.9 Hz, 2H). MS
(EI): m/z 421 [M]C. Anal. Calcd for C25H31N3O3: C, 71.23;
H, 7.41; N, 9.97. Found: C, 71.35; H, 7.54; N, 9.65.
4.1.8. 1,3,5-Tris-pyridin-4-ylmethyl-[1,3,5]triazinane-
2,4,6-trione (13). To a stirred solution of cyanuric acid
(0.13 g, 1.00 mmol), triphenylphosphine (1.30 g, 5.00 mmol)
and 14 (0.55 g, 5.00 mmol) in DMF was added DEAD
(5.00 mmol, 40% in toluene) at room temperature. Stirring
was continued at room temperature for another 5 h, and then
the solvent was removed under reduced pressure. The
resulting residue was triturated with chloroform (100 mL),
and the organic phase was washed with water, brine, and
dried over sodium sulfate. After evaporation of the solvent
in vacuo, the residue was purified by column chromato-
graphy to afford 13 as a white solid (0.29 g, 73%). Mp 198–
200 8C. 1H NMR (400 MHz, CDCl3): d 5.05 (s, 6H), 7.31 (s,
6H), 8.60 (s, 6H). MS (EI): m/z 402 [M]C. Anal. Calcd for
C21H18N6O3$0.5H2O: C, 61.30; H, 4.66; N, 20.43. Found:
C, 61.44; H, 4.51; N, 20.58.
4.1.11.
N-(4-Butyl-phenyl)-N0-pyridin-4-ylmethyl-
[1,3,5]triazine-2,4,6-triamineA (19). A solution of 4-tert-
butylaniline 21 (0.50 g, 3.30 mmol) in THF (5 mL) was
added dropwise over 5 min to an ice-cooled solution of
cyanuric chloride (0.62 g, 3.30 mmol) and DIPEA (2 mL) in
THF (10 mL). The reaction mixture was stirred for 2 h, and
then allowed to warm to room temperature. Ammonia gas
was then bubbled to the solution for 3 h and then hexane
(40 mL) was added. The precipitate resulted was filtered and
washed with hexane to yield a crude product which was
used for next step directly: A suspension of this precipitate,
DIPEA (3 mL) and 4-picolyamine (2 mL) in chloroform and
THF (10 mL, 1:1) was refluxed for 15 h and then
concentrated in vacuo. The resulting residue was triturated
with chloroform (50 mL) and the organic phase washed with
water, brine, and dried over sodium sulfate. After removal
of solvent, the residue was purified by column chromato-
graphy (CHCl2/MeOH 20:1) to give 19 as a yellow solid
(0.46 g, 40%). Mp 113–114 8C. 1H NMR (400 MHz,
CDCl3): d 1.30 (s, 9H), 4.61 (d, JZ6.0 Hz, 2H), 4.95 (s,
2H), 5.59 (br, 1H), 7.02 (s, 1H), 7.23–7.41 (br, m, 8H), 8.56
(d, JZ6.0 Hz, 2H). MS (EI): m/z 349 [M]C. Anal. Calcd for
C19H23N7: C, 65.31; H, 6.63; N, 28.06. Found: C, 65.19; H,
6.69; N, 28.14.
4.1.9. 5-(3-Methyl-butyl)-5-pyridin-4-ylmethyl-pyrimi-
dine-2,4,6-trione (18a). To a stirred solution of diethyl
malonate (8.00 g. 50.0 mmol) in dry DMF (200 mL) was
added sodium hydride (60%, 1.60 g, 40.0 mmol). After
stirring for 30 min, iso-pentyl bromide (5.65 g, 40.0 mmol)
was added in one portion and the reaction mixture was
stirred at room temperature for 3 h. The mixture was con-
centrated in vacuo to afford a oily residue which was tri-
turated with ether (200 mL). The organic phase was washed
with diluted hydrochloric acid, water, brine, and dried with
sodium sulfate. After evaporation of the solvent, the residue
was purified by column chromatography (CHCl3/MeOH,
20:1) to give the desired intermediate in ca. 80% yield. To a
solution of this product (ca. 33 mmol) in dry DMF (100 mL)
was added sodium hydride (60%, 2.80 g, 70.0 mmol) in
portions. After stirring at room temperature for 30 min,
4-(chloromethyl)pyridine (4.17 g, 35.0 mmol) in DMF
(50 mL) was added. The mixture was stirred at 80 8C for
3 h and then concentrated in vacuo. The residue was
triturated with ether (300 mL) and the organic phase was
Acknowledgements
We thank the Ministry of Science and Technology (No.
G2000078101), the National Natural Science Foundation,
and the State Laboratory of Bioorganic and Natural
Products Chemistry of China for financial support. We
also thank Prof. Min Shi for helpful discussion.

9162
X.-B. Shao et al. / Tetrahedron 60 (2004) 9155–9162
22. Whitesides, G. M.; Simanek, E. E.; Mathias, J. P.; Seto,
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