Synthesis of a benzenethiol-derivatized porphyrin for self-assembly

Article abstract of DOI:10.1002/cjoc.201200345

The synthesis of a benzenethiol-derivatized porphyrin for flat-lying self-assembly on gold substrates is described. Acetyl protected thiol is not stable enough in Pd-catalyzed reactions. While acrylate derivatives protected thiol group shows good tolerance in Pd-catalyzed borylations and Suzuki-Miyaura coupling reactions and no catalyst poisoning was observed.

Full text of DOI:10.1002/cjoc.201200345

FULL PAPER
DOI: 10.1002/cjoc.201200345
Synthesis of a Benzenethiol-derivatized Porphyrin for
Self-assembly
Wan, Jicheng(万继成)
Sun, Huiqian(孙会谦)
Huang, Xuebin*(黄学斌)
School of Chemistry, Beijing Institute of Technology, Beijing 100081, China
The synthesis of a benzenethiol-derivatized porphyrin for flat-lying self-assembly on gold substrates is de-
scribed. Acetyl protected thiol is not stable enough in Pd-catalyzed reactions. While acrylate derivatives protected
thiol group shows good tolerance in Pd-catalyzed borylations and Suzuki-Miyaura coupling reactions and no cata-
lyst poisoning was observed.
Keywords porphyrin, thiol, self-assembly
Introduction
Experimental
Porphyrin derivatives as stable organic chromopho-
res that absorb visible light well and luminesce with
high efficiency are excellent candidates as photoelec-
tronic materials in sensors,[1] electronics,[2] organic solar
cells,[3] organic light-emitting diodes,[4] and photocata-
lysts.[5,6] The self-assembly of porphyrins especially
their self-assembled monolayers (SAMs) have attracted
many research interests in recent years.[7-9] In order to
prepare porphyrin SAMs on gold substrates, many por-
phyrin derivatives with thiol or acetyl-protected thiol
groups have been synthesized.[10-14]
The porphyrin SAMs are highly ordered, it is rea-
sonable that some of their properties are anisotropic.
Researchers have demonstrated that the electrical con-
ductivity of LB films of phthalocyanine polysiloxanes is
highly anisotropic.[15] This kind of anisotropy may
greatly affect their application in some devices. For
example, in organic field-effect transistors (OFETs), the
mobility of the phthalocyanine film increased by several
orders of magnitude by ordering in stacks, parallel to the
substrate.[16] Thus to obtain porphyrin SAMs with con-
trolled orientation is of great importance.
In the porphyrin SAMs, most of the porphyrin
molecules adopt an edge-on orientation through one
alkylthiol chain on gold substrates;[17,18] few adopt a
flat-lying orientation through more alkylthiol chains[19,20]
or through intermolecular axial coordination of metal-
loporphyrin to a pre-assembled small functional mole-
cule.[21] In this paper, we designed and synthesized a
benzenethiol-derivatized porphyrin (7) for flat-lying
self-assembly on gold substrates. The conjugated mac-
rocycle of the porphyrin may directly creep on the sub-
strate surface through two meta-positioned benzene-
thiols.
All air and water sensitive reactions were performed
under nitrogen atmosphere. 1H NMR spectra were
measured on a Bruker AVANCE 400 MHz spectrome-
ter using tetramethylsilane (δ 0) as an internal standard.
Mass spectra were measured on a Bruker Daltonics
BIFLEX III MALDI-TOF Analyzer using MALDI
mode. Elemental analyses were carried out using a
FLASH EA1112 elemental analyzer. Electrochemical
measurements were performed with CHI 660 (CH In-
strument, Inc., Austin, USA) electrochemical work-
station at (25±2) ℃, using saturated calomel electrode
(SCE) as the reference electrode, a glassy carbon elec-
trode as the counter electrode, and the porphyrin SAM
on the gold plate as the working electrode.
S-(3-Bromophenyl) ethanethioate (2)
To a
round-bottom-flask were added 3-bromobenzenethiol (1)
(3.8 g, 20 mmol), Mg(ClO4)2 (0.23 g, 1 mmol), Ac2O
(4.12 g, 40 mmol). After stirred at room temperature for
5 h, the reaction mixture was diluted with water and
extracted with dichloromethane. The organic layer was
separated and washed with saturated aqueous NaHCO3
and dried over anhydrous Na2SO4. After evaporation of
the solvent, the crude product was purified by flash
column chromatography (silica gel, petroleum ether) to
afford 2 (3.7 g, 80%) as a colorless crystalline solid. 1H
NMR (CDCl3, 400 MHz) δ: 2.43 (s, 3H), 7.26—7.30 (m,
1H), 7.34—7.36 (m, 1H), 7.52—7.55 (m, 1H), 7.57—
7.58 (m, 1H). Anal. calcd for C8H7BrOS: C 41.58, H
3.05; found C 41.70, H 3.09.
3-Ethylhexyl 3-((3-bromophenyl)thio)propanoate
(3) To a solution of 3-bromobenzenethiol (1) (5.7 g,
30 mmol) in THF (60 mL) were added 2-ethylhexyl
acrylate (5.5 g, 30 mmol) and tetrabutylammonium
fluoride (30 mL, 30 mmol, 1 mol/L in THF). After
*
E-mail: huangxb@bit.edu.cn
Received April 9, 2012; accepted May 10, 2012.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201200345 or from the author.
Chin. J. Chem. 2012, 30, 1841—1844 © 2012 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Wan, Sun & Huang
FULL PAPER
stirred at ambient temperature for 15 h, the mixture was
poured into EtOAc (50 mL) and water (30 mL). The
aqueous layer was extracted with EtOAc (50 mL) and
the combined organic phase was concentrated to dry-
ness. The crude product was purified by flash column
chromatography (silica gel, petroleum ether/ethyl ace-
tate (100/1)) to afford 3 (10.1 g, 90%) as a slightly yel-
backfilled with nitrogen three times. Toluene (5 mL)
was added via syringe, through the septum, followed by
the addition of 4 (252 mg, 0.5 mmol), n-butanol (1 mL),
and water (0.8 mL) in a like manner. The reaction mix-
ture was stired at 80 ℃ for 14 h under nitrogen and
cooled to room temperature. The mixture was poured
into water and the aqueous layer was extracted with di-
chloromethane and the combined organic layer was
concentrated to dryness. The crude product was washed
by methanol, and then purified by column chromatog-
raphy [silica gel, petroleum ether/dichloromethane (1/1)]
1
lowish oil. H NMR (CDCl3, 400 MHz) δ: 0.80—0.92
(m, 6H), 1.15—1.58 (m, 9H), 2.65 (t, J＝7.3 Hz, 2H),
3.19 (t, J＝7.3 Hz, 2H), 4.03 (d, J＝5.8 Hz, 2H), 7.14—
7.18 (m, 1H), 7.27—7.29 (m, 1H), 7.32—7.34 (m, 1H),
7.49—7.50 (m, 1H). Anal. calcd for C17H25BrO2S: C
54.69, H 6.75; found C 54.90, H 6.69.
1
to afford 7 (137 mg, 62%) as a purple solid. H NMR
(CDCl3, 400 MHz) δ: 0.75—0.90 (m, 30H), 1.99—1.21
(m, 138H), 2.80 (t, J＝7.2 Hz, 4H), 3.33 (t, J＝7.2 Hz,
4H), 4.01 (d, J＝6.0 Hz, 4H), 4.08 (t, J＝6.4 Hz, 8H),
4.30 (t, J＝6.8 Hz, 4H), 7.43 (s, 4H), 7.65—7.69 (m,
2H), 7.76 (d, J＝7.6 Hz, 2H), 8.05 (d, J＝7.6 Hz, 2H),
8.19 (s, 2H), 8.93 (d, J＝4.8 Hz, 4H), 9.07 (d, J＝4.8 Hz,
4H). MS (MALDI-TOF) calcd for C138H212N4O10S2Zn
2213, found 2214 (MH+). Anal. calcd for C138H212N4-
O10S2Zn: C 74.77, H 9.64; found C 74.92, H 9.83.
3-Ethylhexyl 3-((3-(4,4,5,5-tetramethyl-1,3,2-di-
oxaborolan-2-yl)phenyl)thio)propanoate (4) A dried
three-necked flask possessing a rubber septum was
charged with PdCl2(CH3CN)2 (42 mg, 2.0%) and Sphos
(L) (272 mg, 8.0%). The mixture was then evacuated
and backfilled with nitrogen three times. 1,4-Dioxane
(4.8 mL) was added via syringe, through the septum,
followed by the addition of 3 (3.08 g, 8 mmol), NEt3 (5
mL) and pinacol borane (1.77 g, 13.8 mmol) in a like
manner. The reaction mixture was stirred at 100 ℃ for
5 h under nitrogen and cooled to room temperature. The
reaction mixture was filtered through a thin pad of
Celite (eluting with ethyl acetate), and the eluent was
concentrated under reduced pressure. The crude product
so obtained was purified via flash chromatography (sil-
ica gel, petroleum ether/ethyl acetate (20/1)) to afford 4
Results and Discussion
The Suzuki-Miyaura reaction has become one of
the most valuable synthetic processes for the construc-
tion of carbon-carbon bonds. meso-Substituted por-
phyrins can be synthesized by modifying the meso-
position of porphyrins through this method conveniently.
3-Bromobenzenethiol (1) and dibromoporphyrin (5)
were chosen as the starting materials for the targeting
benzenethiol-derivatized porphyrin (7).
1
(2.35 g, 70%). H NMR (CDCl3, 400 MHz) δ: 0.79—
0.96 (m, 6H), 1.15—1.60 (m, 21H), 2.62 (t, J＝7.6 Hz,
2H), 3.18 (t, J＝7.6 Hz, 2H), 4.01 (d, J＝5.2 Hz, 2H),
7.26—7.31 (m, 1H), 7.46 (d, J＝7.6 Hz, 1H), 7.65 (d,
J ＝ 7.2 Hz, 1H), 7.81 (s, 1H). Anal. calcd for
C23H37BO4S: C 65.71, H 8.87; found C 65.66, H 8.67.
Compound 6 A dried three-necked flask possess-
ing a rubber septum was charged with PdCl2(PPh3)2 (12
mg, 0.017 mmol) and porphyrin 5 (232 mg, 0.13 mmol).
The mixture was then evacuated and backfilled with
nitrogen three times. 1,2-Dichloroethane (10 mL) was
added via syringe through the septum, followed by ad-
dition of NEt3 (0.5 mL) and pinacol borane (333 mg, 2.6
mmol) in a like manner. The reaction mixture was stired
at 90 ℃ for 45 min under nitrogen, then cooled to
room temperature, quenched with 30% aq KCl (30 mL),
and washed with water. After evaporation of the sol-
vent , the residue was purified by column chromatogra-
phy (silica gel, petroleum ether/dichloromethane (1/3))
Scheme 1 Protection of thiol
Ac2O
Br
SAc
2 (80%)
Mg(ClO4)2, r.t.
Br
SH
1
2-ethylhexyl acrylate
TBAF, THF, r.t.
Br
SR
3 (90%)
O
R =
O
The synthetic route to the targeting compound (7) is
shown in Schemes 1—3. Dibromoporphyrin (5) was
synthesized according to our previous work by acid-
catalyzed condensation of benzaldyhyde and pyrrol fol-
lowed by bromation reaction with NBS.[22] Free thiols
cannot be used directly in Pd-catalyzed reactions for
their poisoning effect on the catalysts. Protection of
thiol 1 was carried out through two methods (Scheme 1).
Thiol 1 afforded compound 2 by reacting with acetic
anhydride under room temperature in 80% yield; af-
forded compound 3 by reacting with 2-ethylhexyl acry-
1
to afford 6 as a purple solid (208 mg, 85%). H NMR
(CDCl3, 400 MHz) δ: 0.80—0.90 (m, 18H), 1.15—1.70
(m, 120H), 1.84 (s, 24H), 4.09 (t, J＝6.4 Hz, 8H), 4.31
(t, J＝6.4 Hz, 4H), 7.50 (s, 4H), 9.18 (d, J＝4.8 Hz 4H),
9.91 (d, J＝4.4 Hz, 4H). MS (MALDI-TOF) calcd for
C116H186B2N4O10Zn 1881, found 1882 (MH+).
Compound 7 A three-necked flask possessing a
rubber septum was charged with Pd(PPh3)4 (52 mg,
0.045 mmol), Cs2CO3 (520 mg, 1.6 mmol) and 5 (178
mg, 0.1 mmol). The mixture was then evacuated and
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Chin. J. Chem. 2012, 30, 1841—1844

Synthesis of a Benzenethiol-derivatized Porphyrin for Self-assembly
late under room temperature in 90% yield.
The PdCl2(CH3CN)2/Sphos (L) catalyst system is highly
efficient in the borylation of a range of aryl and hetero-
aryl bromides.[25] When the above catalyst system is
used, a higher yield 70% was realized. Compound 6 is
readily obtained via borylation of dibromoporphyrin 5
using PdCl2(PPh3)2 as the catalyst in 85% yield.[26]
Scheme 3 illustrates the Suzuki-Miyaura coupling
reaction between aryl bromides and boronates. When
porphyrin boronate 6 was used, neither protected thiol 2
nor 3 afforded the desired product with Pd(PPh3)4 as
catalyst and K2CO3 as base in DME or in DMF/toluene
at 85 ℃. This can be explained by unstable thiol pro-
tecting group and low activity of the bromide respec-
tively.
Scheme 2 presents borylation reaction of aryl bro-
mides including dibromoporphyrin 5. Borylation of
acetyl-protected thiol 2 proved to be unsuccessful, no
desired product was separated. It should be explained
that acetyl-protected thiols are not stable enough under
aqueous basic conditions and the Pd-catalysts are deac-
tivated by the free thiols produced under the reaction
condition.[23] 2-Ethylhexyl acrylate is found to be a
good protecting group for arylthiols, which demon-
strates good tolerance in Pd-catalyzed coupling reac-
tions under aqueous or anhydrous basic conditions, and
it could be removed via β-elimination reaction.[24]
Scheme 2 Borylation of aryl bromides
Scheme 3 Synthesis of the thiol-derivatized porphyrins
OC12H25
Pinacolborane
SR
C12H25
O
OC12H25
O
B
Pd(PPh3)2Cl2, NEt3
O
3
ClCH2CH2Cl, 100oC
4 (20%)
O
N
N
N
N
Pd(PPh3)4, K2CO3
DMF/toluene, 85 oC
Zn
4 + 5
R =
O
Pinacolborane
RS
SR
PdCl2(CH3CN)2 : L, NEt3
4 (70%)
3
Dioxane,100 oC
C12H25
O
OC12H25
OC12H25
7 (10%)
PCy2
OMe
L =
MeO
Br
O
R =
OC12H25
C12H25
C12H25
C12H25
O
O
N
N
N
N
Zn
OC12H25
OC12H25
O
Pd(PPh3)4, Cs2CO3
4 + 5
7 (62%)
O
PhMe, n-BuOH, H2O
Br
Pd(PPh3)4-catalyzed coupling reaction between bo-
ronate 4 and dibromoporphyrin 5 was carried out under
different conditions. When the commonly used base
K2CO3 was used, the desired product 7 was obtained in
low yield (10%).[27] When Cs2CO3 was used as the base,
a higher 62% yield was obtained.[28] Because of the low
solubility of dibromoporphyrin 5, the Pd-catalyzed cou-
pling reactions have to be performed with dilute solu-
tions, and need a greater proportion of aryl boronate
ester, catalyst and base.
Aromatic thiols are usually unstable, easily oxidized,
and proved difficult to be used in actual surface deposi-
tion experiments.[29,30] So we tried to use the protected
thiol-derivatized porphyrin 7 to prepare SAMs, and pre-
liminary electrochemical results show that stable SAMs
of 7 on gold electrodes have been obtained. Figure 1
presents cyclic voltmmograms of (a) a SAM of porphy-
rin 7 on Au and (b) bare Au in CH2Cl2/0.1 mol/L
[n-Bu4N]＋[PF6]－ solution. Three reduction peaks ap-
peared for the Au electrode after immersion in a chlo-
5
Pinacolborane
Pd(PPh3)2Cl2, Et3N
ClCH2CH2Cl, 100 oC
O
O
B
C12H25
O
OC12H25
OC12H25
OC12H25
N
N
N
N
C
12H25O
Zn
C12H25
O
B
O
O
6 (85%)
Borylation of aryl bromide 3 using PdCl2(PPh3)2 as
the catalyst afforded compound 4 in low yield (20%).
Chin. J. Chem. 2012, 30, 1841—1844
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1843

Wan, Sun & Huang
FULL PAPER
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Figure 1 Cyclic voltammograms of (a) a SAM of porphyrin 7
on Au and (b) bare Au in CH2Cl2/0.1 mol/L [n-Bu4N]＋[PF6]－.
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Conclusions
In summary, we successfully synthesized a novel
porphyrin containing two rigid thiol groups which may
make the porphyrin molecules directly creep on the
substrate surface and minimize the distance between the
macrocycle and the gold surface when used for prepar-
ing SAMs. Preliminary electrochemical results show
that porphyrin 7 can form stable SAMs on gold elec-
trodes. We hope our work will be helpful in the con-
struction and application of porphyrin-based SAMs.
[22] Huang, X. B.; Zhu, C. L.; Zhang, S. M.; Li, W. W.; Guo, Y. L.;
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Acknowledgement
This work was supported by the NSFC (Nos.
50973011 and 20702004).
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