Synthesis of trichlorodimethoxybenzene-linked porphyrin-pyridine conjugate

Article abstract of DOI:10.1055/s-2000-7599

The synthesis of a trichlorodimethoxybenzene substituted Zn(II) metalloporphyrin-pyridine conjugate 12 is reported. The structures of the porphyrins were established by MS, ¹H NMR and elemental analysis. Protonation of the pyridine moiety leads to a strong reduction of fluorescence intensity of 12.

Full text of DOI:10.1055/s-2000-7599

PAPER
1543
Synthesis of Trichlorodimethoxybenzene-Linked Porphyrin-Pyridine
Conjugate
Takashi Arimura,*a Yasuhiro Suga,a Kochurani Jacob,a Hideki Sugihara,a Shigeo Murata,a Hirohisa Tsuzukib
a COE Laboratory, National Institute of Materials and Chemical Research, Tsukuba 305-8565, Japan
b Center of Environmental Analysis, Tohwa University, Fukuoka 815-8510, Japan
Fax +81298557357; E-mail:takashi@home.nimc.go.jp
Received 4 November 1999; revised 30 May 2000
CH3COOK
(CH3CO)2O
OCH3
CH=CHCOOH
OCH3
CHO
Abstract: The synthesis of a trichlorodimethoxybenzene substitut-
ed Zn(II) metalloporphyrin-pyridine conjugate 12 is reported. The
structures of the porphyrins were established by MS, 1H NMR and
elemental analysis. Protonation of the pyridine moiety leads to a
strong reduction of fluorescence intensity of 12.
H2
,
Pd/C
Cl
Cl
Cl
Cl
Cl
OCH3
Et2O
Cl
OCH3
(81%)
(85%)
1
2
Key words: porphyrin, pyridine, electron transfer, conjugation, su-
pramolecular chemistry
O
C
OCH3
CH2CH2COOH
OCH3
1.
SOCl2
Cl
Cl
R
Cl
Cl
N
H
Porphyrins are remarkable coordinating ligands since
they form metallocomplexes with almost all of the metals
of the periodic table.1 The considerable progress achieved
in porphyrin chemistry can be attributed to the extensive
studies carried out on the syntheses of variously substitut-
ed porphyrin derivatives.2 We are interested in designing
a series of donor-bridge-acceptor systems to give infor-
mation on how the nature of the spacer between the donor
and the acceptor influences the electron transfer process.3
In this paper, we report the synthesis of a porphyrin do-
nor-bridge-acceptor system. The donor and the acceptor
are zinc porphyrin and trichlorodimethoxybenzene,4 re-
spectively.
Cl
OCH3
Cl
OCH3
2. R-NH2
3
R =
4a (72%);
4b (86%);
N
NH2
NH2
R =
Scheme 1
similar manner. The syntheses of 12 and 13 are shown in
Scheme 3. Hydrolysis of 8 with NaOH in H2O/dioxane
followed by treatment with SOCl2 and 4a in CH2Cl2 af-
forded the target compound 12 in 53% yield. Compound
12 was verified by spectroscopic analyses including H
NMR and MALDI-TOF mass spectra. The porphyrin 13
was prepared from 4b and 8 in 76% yield.
In Scheme 1, the synthetic route to the functionalized
trichlorodimethoxybenzene 4 is shown. The starting com-
pound 1 was prepared in five steps from 2,5-dihydroxytol-
uene according to the reported methods.5 Perkin reaction
of 1 and acetic anhydride with potassium acetate gave the
cinnamic acid 2 in 81% yield. Reduction of 2 in the pres-
ence of palladium-on-charcoal afforded the propionic acid
3 in 85% yield. Chlorination of 3 with SOCl2 followed by
treatment with 2,6-diaminopyridine and 1,3-phenylenedi-
amine in Et2O gave 4a and 4b in 72% and 86% yields, re-
spectively.
1
The absorption spectra of the zinc complex 12 exhibited
Soret band (S2) at 407 nm and Q bands (S1) at 535 nm and
571 nm in CH2Cl2, while the absorption spectra of the zinc
complex 13 showed Soret band at 423 nm and Q bands at
550 nm and 588 nm in CH2Cl2, respectively. The fluores-
cence emission bands of 12 exhibited at 576 nm and 627
nm in CH2Cl2, and those of 13 showed at 600 nm and 648
nm in CH2Cl2. The absorption and fluorescence spectra of
12 and 13 are almost identical with the corresponding ref-
erence compounds 8 and 11, respectively, suggesting that
the attachment of the trichlorodimethoxybenzene to the
porphyrin moiety does not perturb its electronic property.
In Scheme 2, the syntheses of 8 and 11 are shown. Previ-
ously published procedures were used for the syntheses of
3,3¢-dimethyl-4,4¢-diethyldipyrromethane (5)3b and ethyl
4¢-formyl-4-biphenylcarboxylate (6).6 The porphyrin 8
was prepared in 22% yield from the cross-condensation of
5, 6, and benzaldehyde (7). The porphyrin 8, however,
showed low solubility in the organic solvent, which made
the purification by silica gel column chromatography dif-
ficult and caused a low yield. Therefore, meso-(3,5-di-
tert-butylphenyl)-2,2¢-dipyrromethane (9)7 and 3,5-di-
tert-butylbenzaldehyde (10) were employed to provide
enhanced solubility to the porphyrin. The porphyrin 11
was synthesized from 6, 9, and 10 in a 28% yield in the
Bubbling of HCl through a CH2Cl2 solution of 12 fol-
lowed by treatment with Zn(OAc)2 led to a decrease in the
electronic absorption at 290 nm and the formation of a
new maximum at 320 nm, reflecting the protonation of the
pyridine ring, and that the fluorescence intensity of 12 was
strongly reduced. Moreover, changes in the absorption
Synthesis 2000, No. 11, 1543–1546 ISSN 0039-7881 © Thieme Stuttgart · New York

1544
T. Arimura et al.
PAPER
1. TCA, Chloranil
CH3CN
CO2Et
2. Zn(OAc)2
CH2Cl2-MeOH
N
N
N
Zn
CO2Et
+
+
N
H
N
N
H
CHO
(22%)
CHO
7
8
6
5
t-Bu
t-Bu
t-Bu
t-Bu
t-Bu
N
N
N
t-Bu
t-Bu
Zn
CO2Et
t-Bu
t-Bu
CHO
N
N
H
N
H
t-Bu
9
10
11
Scheme 2
1. aq NaOH , Dioxane
2. SOCl2 , CH2Cl2
3. 4a , CH2Cl2
H
N
H
MeO
Cl
Cl
Cl
OMe
N
N
N
N
N
Zn
C
O
C
O
8
N
(53%)
12
t-Bu
t-Bu
H
H
N
MeO
Cl
t-Bu
t-Bu
t-Bu
Cl
Cl
OMe
N
Zn
N
N
C
C
O
N
N
O
t-Bu
13
Scheme 3
spectrum and the fluorescence spectrum of 13 were not that the pyridine moiety might play an important role in
observed upon bubbling HCl into a CH2Cl2 solution of 13. the fluorescence quenching process.
Interestingly, the C=O stretching vibration (1690 cm-1) in
12 was shifted to a lower wavenumber region by about 30
Mps were determined with an electrothermal melting point appara-
cm-1, indicating the formation of two intramolecular hy-
tus in a sealed capillary and are uncorrected. UV-visible spectra
were obtained with a Shimadzu UV-3101PC spectrometer. Steady-
drogen bonds to the carbonyl oxygens (Figure). Although
the detailed quenching mechanism of 12 is not clear, one
might assume that the resulting conformation (12B)
caused a static quenching process. The present paper out-
lines the synthesis of trichlorodimethoxybenzene substi-
tuted Zn(II) metalloporphyrin-pyridine conjugate 12 and
state fluorescence spectra were taken on a Shimadzu RF-5301PC
spectrofluorimeter. H NMR spectra were measured on a Varian
XL-300 spectrometer, and the chemical shifts (d) are reported in
ppm, referenced to TMS as an internal standard. FAB and MALDI-
TOF mass spectra were recorded on JEOL-DX303 and PerSeptive
Biosystems JMS-ELITE, respectively. All chemicals were reagent
1
Synthesis 2000, No. 11, 1543–1546 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Trichlorodimethoxybenzene-Linked Porphyrin-Pyridine Conjugate
1545
3-[2,4,5-Trichloro-3,6-dimethoxybenzene]-N-(6-amino-2-py-
ridyl)propanamide (4a)
12
After a mixture of 3 (1.0 g, 3.20 mmol) and thionyl chloride
(0.60 g, 5.04 mmol) was stirred at 70 ∞C for 0.5 h, the excess thionyl
chloride was distilled in vacuo to afford the acid chloride as a yel-
low oil (verified by IR spectra). The yellow residue was dissolved
in Et2O (100 mL) and 2,6-diaminopyridine (0.70 g, 6.41 mmol) was
added. After stirring for 3 h, the mixture was washed with dilute
HCl and H2O, and dried (Na2SO4). Purification by column chroma-
tography on silica gel (CH2Cl2-hexane) gave 0.93g (72%) of 4a as
colorless flakes, mp: 60-62 ∞C.
H+
H
N
H
N
H
N
MeO
Cl
Cl
Cl
OMe
+
N
N
N
Zn
C
O
C
O
N
1H NMR (300 MHz, CDCl3): d = 2.59 (t, 2H, J = 7.8 Hz, Ar-
CH2CH2), 3.21 (t, 2H, J = 7.8 Hz, Ar-CH2CH2), 3.87, 3.88 (s, each
3H, OCH3), 4.29 (br s, 2H, NH2), 6.26 (d, 1H, J = 8 Hz, pyridine-
H), 7.47 (t, 1H, J = 8 Hz, pyridine-H), 7.54 (br s, 2H, pyridine-H
and NHCO).
12A
MS (FAB): m/z = 404 (M+).
Anal. Calcd for C16H16Cl3N3O3: C, 47.49; H, 3.98; N, 10.38. Found:
C, 47.50; H, 3.69; N, 10.00.
N
Zn
N
N
Cl
N
MeO
Cl
3-[2,4,5-Trichloro-3,6-dimethoxybenzene]-N-(6-aminoben-
zene)propionamide (4b)
Compound 4b was prepared from 3 and 1,3-phenylenediamine in
the similar manner as for 4a.
OMe
Cl
O
O
+
C
C
N
H
N
N
H
H
Colorless needles, mp: 188-189 ∞C.
1H NMR (300 MHz, CDCl3): d = 2.58 (t, 2H, J = 8.1 Hz, Ar-
CH2CH2), 3.21 (t, 2H, J = 8.1 Hz, Ar-CH2CH2), 3.69 (br s, 2H,
NH2), 3.87 (s, 6H, OCH3), 6.41-6.44 (m, 1H, ArH), 6.64-6.67 (m,
1H, ArH), 7.07 (t, 1H, J = 8.4 Hz, ArH), 7.17 (br s, 1H, NHCO)
7.19 (br s, 1H, ArH).
12B
Figure Effect of protonation on hydrogen bonding orientation
MS (FAB): m/z = 403 (M+).
grade and used without further purification. THF was freshly dis-
tilled from Na/benzophenone ketyl, while CH2Cl2 was distilled over
CaH2. All reactions were carried out in a N2 atm.
Anal. Calcd for C17H17Cl3N2O3: C, 50.58; H, 4.24; N, 6.94. Found:
C, 50.58; H, 4.16; N, 6.79.
Zn(II) Complex of 5-Phenyl-15-(4-(4’-ethoxycarbonylbiphe-
nyl))-2,8,12,18-tetraethyl-3,7,13,17-tetramethylporphyrin (8)
To a stirred mixture of 3,3¢-dimethyl-4,4¢-diethyldipyrromethane
(5) (238 mg, 1 mmol), ethyl 4¢-formyl-4-biphenylcarboxylate (6)
(127 mg, 0.50 mmol), and benzaldehyde (7, 53 mg, 0.50 mmol) in
MeCN (10 mL) was added trichloroacetic acid (56 mg, 0.34 mmol).
The mixture was stirred overnight at r.t. in the dark. p-Chloranil
(400 mg, 1.63 mmol) dissolved in THF (20 mL) was added, and the
stirring was continued for 5 h, then the solution was poured into
H2O and extracted with CH2Cl2. To the organic extracts, sat.
Zn(OAc)2/MeOH solution (5 mL) was added and the solution was
refluxed for 2 h. The mixture was washed with H2O, dried
(Na2SO4), and evaporated in vacuo to leave a residue, which was
purified by silica gel column chromatography (CH2Cl2-hexane) to
afford 92 mg (22%) of 8 as purple prisms, mp: > 300 ∞C.
2,4,5-Trichloro-3,6-dimethoxycinnamic Acid (2)
After a mixture of 1 (2.01 g, 7.46 mmol), potassium acetate (0.69 g,
6.98 mmol) and acetic anhydride (12.85 g, 125.9 mmol) was stirred
at 130 ∞C for 3 h, it was diluted with H2O. Na2CO3 was added to the
aqueous suspension. After filtration, concd HCl was added to the
filtrate. The precipitate was filtered off and washed with H2O to
give 1.88 g (81%) of 2 as white needles, mp: 214-216 ∞C.
1H NMR (300 MHz, CDCl3): d = 3.80, 3.90 (s, each 3H, OCH3),
6.90 (d, 1H, J = 16.2 Hz, Ar-CH = CH), 7.95 (d, 1H, J = 16.2 Hz,
Ar-CH = CH), 12.84 (br s, 1H, COOH).
MS (FAB): m/z = 311 (M+).
Anal. Calcd for C11H9Cl3O4: C, 42.38; H, 2.89. Found: C, 42.30; H,
2.73.
1H NMR (300 MHz, CDCl3): d = 0.84 (t, 3H, J = 6.9 Hz,
CO2CH2CH3), 1.76 (m, 12H, pyrrole-CH2CH3), 2.44, 2.54 (s, each
6H, pyrrole-CH3), 3.77 (q, 2H, J = 6.9 Hz, CO2CH2CH3), 3.98 (m,
8H, pyrrole-CH2CH3), 6.89-8.25 (m, 13H, ArH), 10.14 (s, 2H,
meso-H).
3-[2,4,5-Trichloro-3,6-dimethoxybenzene]propionic Acid (3)
A mixture of 2 (0.90 g, 2.89 mmol), palladium-on-charcoal (0.3 g),
and Et2O (60 mL) was stirred vigorously for 3 h under H2 pressure,
then filtered through Celite. The filtrate was evaporated to afford
0.77 g (85%) of 3 as colorless needles, mp: 149-151 ∞C.
1H NMR (300 MHz, CDCl3): d = 2.63 (t, 2H, J = 8.4 Hz, Ar-
CH2CH2), 3.14 (t, 2H, J = 8.4 Hz, Ar-CH2CH2), 3.86, 3.88 (s, each
3H, OCH3).
MS (FAB): m/z = 841 (M+).
Anal. Calcd for C53H52N4O2Zn∑0.5H2O: C, 74.77; H, 6.27; N, 6.58.
Found: C, 74.53; H, 6.12; N, 6.43.
MS (FAB): m/z = 313 (M+).
Compound 11
Anal. Calcd for C11H11Cl3O4∑0.3H2O: C, 41.34; H, 3.68. Found: C,
41.39; H, 3.19.
Compound 11 was prepared from 6, 9, and 10 in the similar manner
as for 8.
Purple powder, mp: > 300 ∞C.
Synthesis 2000, No. 11, 1543–1546 ISSN 0039-7881 © Thieme Stuttgart · New York

1546
T. Arimura et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 0.92 (t, 3H, J = 7.3 Hz,
CO2CH2CH3), 1.53 (m, 54H, t-Bu), 4.45 (q, 2H, J = 7.3 Hz,
CO2CH2CH3), 7.80 (t, 3H, J = 2 Hz, ArH), 8.02 (m, 4H, biphenyl-
H), 8.10 (m, 6H, ArH), 8.25 (d, 2H, J = 8.1 Hz, biphenyl-H), 8.35
(d, 2H, J = 8.1 Hz, biphenyl-H), 9.02 (m, 8H, pyrrole-H).
Compound 13
Compound 13 was prepared from 4b and 8 in the similar manner as
for 12.
Purple powder, mp: 229-231 ∞C.
1H NMR (300 MHz, CDCl3): d = 1.53 (s, 54H, t-Bu), 2.65 (t, 2H,
J = 8.4 Hz, Ar-CH2CH2), 3.25 (t, 2H, J = 8.4 Hz, Ar-CH2CH2), 3.91
(s, 6H, OCH3), 7.00-7.30 (m, 4H, ArH), 7.53 (br s, 2H, NH), 7.80
(d, 3H, J = 1.8 Hz, ArH), 8.05 (d, 4H, J = 8 Hz, biphenyl-H), 8.10
(m, 6H, ArH), 8.37 (d, 4H, J = 8 Hz, biphenyl-H), 9.02, 9.03 (s,
each 4H, pyrrole-H).
MS (FAB): m/z = 1162 (M+).
Anal. Calcd for C77H84N4O2Zn∑H2O: C, 78.32; H, 7.34; N, 4.74.
Found: C, 78.06; H, 7.57; N, 4.30.
Compound 12
MS (FAB): m/z 1520 (M+).
After a mixture of 8 (200 mg, 0.24 mmol), NaOH (40 mg,
1.0 mmol), and dioxane (20 mL) was refluxed for 2 h, the solution
was poured into H2O containing concd HCl, extracted with CHCl3,
and neutralized with aqueous NaHCO3. To the organic extracts, sat.
Zn(OAc)2/MeOH solution (5 mL) was added and the solution was
refluxed for 1 h. The mixture was washed with H2O and evaporated
in vacuo to afford the porphyrin carboxylic acid (verified by IR
spectra). After a mixture of the porphyrin carboxylic acid and thio-
nyl chloride (0.5 g, 4.2 mmol) was stirred at 80 ∞C for 0.5 h, the ex-
cess thionyl chloride was distilled in vacuo. The residue dissolved
in CH2Cl2 (10 mL) was added to a solution of the propionamide 4a
(100 mg, 0.25 mmol) in CH2Cl2 (30 mL). The solution was stirred
for 3 h, and evaporated in vacuo to leave the residue, which was
worked up as described for the preparation of 8 to afford 153 mg
(53%) of 12 as purple prisms, mp: > 300 ∞C.
1H NMR (300 MHz, CDCl3): d = 1.90 (m, 12H, pyrrole-CH2CH3),
2.45, 2.55 (s, each 6H, pyrrole-CH3), 2.66 (t, 2H, J = 7.2 Hz, Ar-
CH2CH2), 2.95 (t, 2H, J = 7.5 Hz, Ar-CH2CH2), 3.76, 3.79 (s, each
3H, OCH3), 4.03 (m, 8H, pyrrole-CH2CH3), 6.51 (d, 1H, J = 6.2 Hz,
pyridine-H), 6.69-8.32 (m, 15H, pyridine-H and ArH), 10.09,
10.17 (s, each 1H, meso-H).
Anal. Calcd for C92H95Cl3N6O4Zn∑0.5CHCl3: C, 70.31; H, 6.09; N,
5.32. Found: C, 70.09; H, 6.13; N, 5.09.
References
(1) Guilard, R.; Lecomte, C.; Kadish, K. M. Struct. Bonding
1987, 64, 205.
(2) Dolphin, D. The Porphyrins; Academic: New York, 1978.
(3) a) Arimura, T.; Brown, C. T.; Springs, S. L.; Sessler, J. L.
Chem. Commun. 1996, 2293.
b) Arimura, T.; Ide, S.; Sugihara, H.; Murata, S.; Sessler, J. L.
New J. Chem. 1999, 23, 977.
(4) Osuka, A.; Zhang, R. P.; Maruyama, K.; Yamazaki, I.;
Nishimura, Y. Bull. Chem. Soc. Jpn. 1992, 65, 2807.
(5) Wallenfels, K.; Hofmann, D.; Kern, R. Tetrahedron 1965, 21,
2231.
(6) Craig, J. C.; Loder, J. W. J. Chem. Soc. 1965, 100.
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Article Identifier:
1437-210X,E;2000,0,11,1543,1546,ftx,en;F07099SS.pdf
MS (MALDI-TOF): 1073.13 (M-2OCH3-Zn).
Anal. Calcd for C67H62Cl3N7O4Zn∑H2O: C, 66.02; H, 5.29; N, 8.04.
Found: C, 65.84; H, 4.99; N, 7.98.
Synthesis 2000, No. 11, 1543–1546 ISSN 0039-7881 © Thieme Stuttgart · New York