The preparation of rigid linear Di- (and Tri-)catechol derivatives

Article abstract of DOI:10.1055/s-2000-7604

The aryl-bridged rigid rod-like di- and tricatechol ligands 1-5 were prepared by aryl-aryl coupling reactions. Hereby either Suzuki coupling strategies [starting with 2,3-dimethoxyphenylboronic acid (6) as an important building block] or oxidative couplin

Full text of DOI:10.1055/s-2000-7604

PAPER
1557
The Preparation of Rigid Linear Di- (and Tri-)catechol Derivatives
Markus Albrecht,* Matthias Schneider
Institut für Organische Chemie, Universität Karlsruhe, Richard-Willstätter-Allee, D-76131 Karlsruhe, Germany
Fax +49(721)698529; E-mail: albrecht@ochhades.chemie.uni-karlsruhe.de
Received 25 May 2000; revised 11 July 2000
Abstract: The aryl-bridged rigid rod-like di- and tricatechol ligands
1-5 were prepared by aryl–aryl coupling reactions. Hereby either
Suzuki coupling strategies [starting with 2,3-dimethoxyphenylbo-
ronic acid (6) as an important building block] or oxidative coupling
with methyltributylammonium permanganate were used to obtain
the desired compounds.
Key words: catechol, chelating ligands, Suzuki coupling, oxidative
coupling, ether cleavage
During the last 15 years the chemistry of double- and tri-
ple-stranded helicates has become an important field of
supramolecular research.1 Many different ligand systems
were tested for their ability to form linear oligonuclear co-
Figure 1 Structures of catechol ligands 1-3
ordination compounds in metal-directed self-assembly
processes. However, most of the ligands possess either
flexible spacers which connect the ligand moieties or the
helicity of the oligonuclear complex already is embodied
in a rigid ligand.2 There are few examples described,
where rigid linear ligands were used in the formation of
helicates.3
2,2’,3,3’-tetrol (1) is obtained in quantitative yield as a
yellow, slightly hygroscopic solid (Scheme 1).
The introduction of a p-phenylene spacer is achieved by
Suzuki coupling of the boronic acid 6 with 1,4-dibro-
mobenzene (9) [Pd(PPh3)4, Na2CO3]. The ligand precur-
sor 10 is obtained in 38% yield and by reaction with BBr3
in 91% is transformed into 1,1’:4’,1”-terphenyl-2,2”,3,3”-
tetrol (2).4 4,4’-Dibromo-1,1’-biphenyl (11) is coupled
with two equivalents of 6 to obtain the linear derivative 12
in 57% yield. Reaction of 12 with BBr3 leads to
1,1’:4’,1”:4”,1’”-quaterphenyl-2,2”’,3,3’”-tetrol (3) in
quantitative yield.
Recently we communicated the synthesis of the rigid p-
phenylene-bridged dicatechol ligand 2 which forms a tri-
ple-stranded helicate with titanium(IV) ions in the pres-
ence of an appropriate base.4,5 Herein we describe the
synthetic details for the preparation of 2 as well as of the
derivatives 1 and 3-5. In the compounds 1-3 the size of
the rigid system is systematically varied. The dicatechol 1
possesses a length of approximately 9.2 Å.6 The p-phe-
nylene-bridged compound 2 is 13.5 Å and the 4,4’-substi-
tuted 1,1’-biphenylene derivative 3 is 17.8 Å long (Figure
1). In 1,1’:4’,1”-terphenyl-2,2’,2”,3,3’,3”-hexol (4) three
catechol units are linearly connected. The compounds 1-
4 are all synthesized by Suzuki-coupling strategies, while
the ligand 5, which bears two additional methyl groups,
was prepared by symmetric oxidative coupling of two ar-
omatic moieties.
The tricatechol derivative 4 is obtained by reaction of bo-
ronic acid 6 with 1,4-dibromo-2,3-dimethoxybenzene
(13) (prepared from veratrole)9 in the presence of
Pd(PPh3)4 and sodium carbonate (Scheme 2). The double
Suzuki coupling yields 14 in 28%. The low yield of cou-
pling product 14 might be due to the close proximity of the
two coupling positions which are located at the same aro-
matic nucleus. Similar yields were observed for the prep-
aration of the analogous 10, while in the preparation of the
larger compound 12 a better yield of 57% is achieved.
However, much better yields were described in the litera-
ture for Suzuki coupling reaction in related systems.5 The
ligand precursor 14 is deprotected quantitatively by reac-
tion with BBr3 to afford 1,1’:4’,1”-terphenyl-
2,2’,2”,3,3’,3”-hexol (4).
The dicatechol ligands 1-3 were prepared by Suzuki
coupling7 using the boronic acid derivative 6, which was
prepared according to a procedure described by Weiss et
al.8 Refluxing a mixture of 6, 2,3-dimethoxybromoben-
zene (7) (prepared from veratrole as described earlier),9
tetrakis(triphenylphosphane)palladium(0) (0.033 equiv)
and sodium carbonate in toluene leads to the formation of
2,2’,3,3’-tetramethoxy-1,1’-biphenyl (8). After chro-
matographic workup (silica gel, CH2Cl2), compound 8 is
obtained in 61% yield. The methyl ethers of 8 are cleaved
by reaction with BBr3 and the ligand 1,1’-biphenyl-
As an alternative for the preparation of tetrahydroxybi-
phenyl derivatives, an oxidative coupling reaction can be
applied. Hereby 2-methoxy-4-methylphenol (15) is oxi-
datively coupled, using methyltributylammonium per-
manganate (MTBAP)10 as the oxidizing reagent. The
Synthesis 2000, No. 11, 1557–1560 ISSN 0039-7881 © Thieme Stuttgart · New York

1558
M. Albrecht, M. Schneider
PAPER
Oxidative approach to the dicatechol derivative 5 (MTBAP = me-
thyltributylammonium permanganate)
Scheme 3
The dicatechol derivatives 1 and 5 possess a structural
moiety which also is found in the natural occurring masti-
gophorenes A and B (Figure 2). However, it is not known,
if the binding of the mastigophorenes to metal ions might
be important for their biological activity.11
Figure 2
Preparation of the dicatechol derivatives 1-3 by Suzuki coupling
In summary we have presented the synthesis of four rigid
rod-like dicatechol ligands 1-3 and 5 and of the linear tri-
catechol derivative 4. In the key step of the reaction se-
quences Suzuki coupling procedures were used to obtain
the linear di-, tri,- or tetraaryl systems or as an alternative
two building blocks were coupled oxidatively by use of
MTBAP. The reaction sequences which lead to the de-
sired oligocatechol ligands are short and allow the prepa-
ration of large amounts of the derivatives. The behavior of
1-5 in metal-directed self-assembly processes is currently
investigated in our laboratories.
Scheme 1
obtained ligand precursor 16 is used without purification
and 5,5’-dimethyl-1,1’-biphenyl-2,2’,3,3’-tetrol (5) is ob-
tained in 92% yield after ether cleavage with BBr3
(Scheme 3).
1H NMR and 13C NMR spectra were recorded on a Bruker DRX 500
spectrometer using DEPT techniques for the assignment of the mul-
tiplicity of carbon atoms. FT-IR spectra were recorded by diffuse
reflection (KBr) on a Bruker IFS spectrometer. UV-vis spectra were
recorded on a Perkin Elmer Lambda 2 spectrometer. Mass spectra
(EI, 70 eV) were taken on a Finnigan MAT 90 mass spectrometer.
Elemental analyses were obtained with a Heraeus CHN-O-Rapid
analyzer. Solvents were purified by standard methods. Melting
points: Büchi 535 (uncorrected). Air sensitive compounds were pre-
pared and handled under Ar using Schlenk techniques. 2,3-
Dimethoxyphenylboronic acid (6),8 3-bromoveratrole (7),9 and 3,6-
dibromoveratrole (13)9 were prepared by published procedures.
Preparation of the tricatechol derivative 4 by Suzuki coupling
Scheme 2
Synthesis 2000, No. 11, 1557–1560 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
The Preparation of Rigid Linear Di- (and Tri-)catechol Derivatives
1559
2,2’,3,3’-Tetramethoxy-1,1’-biphenyl (8)
13C NMR (CDCl3): d = 153.2 (C), 146.7 (C), 137.0 (C), 135.7 (C),
129.0 (CH), 124.1 (CH), 122.7 (CH), 111.5 (CH), 60.7 (CH3), 56.0
(CH3).
3-Bromoveratrole (7;9 650 mg, 3.0 mmol) and Pd(PPh3)4 (120 mg,
0.01 mmol) were dissolved in toluene (20 mL) and successively 2
M aq Na2CO3 solution (3.5 mL) and 2,3-dimethoxyphenylboronic
acid (6; 560 mg, 3.07 mmol) in EtOH (5 mL) were added. After re-
fluxing overnight the mixture was washed with aq Na2CO3 solution,
dried (MgSO4) and solvent was removed under vacuum. The crude
product of 8 was purified by column chromatography (silica gel,
CH2Cl2); yield: 508 mg (61%); yellow solid; mp 98 °C (CH2Cl2).
IR (KBr): n = 3447, 3104, 3007, 2841, 1597, 1579, 1480, 1427,
1398, 1268, 1228, 1017, 1005, 838, 754, 652 cm-1.
UV/vis (MeOH): l (e) = 204 (53800), 266 nm (25600).
MS: m/z (%) = 350 (100) [M]+.
HRMS (EI, 70 eV): C22H22O4 (350.4): m/z calcd: M 350.1518;
1H NMR (CDCl3): d = 7.09 (t, J = 7.9 Hz, 2 H), 6.95 (dd, J = 7.9,
1.5 Hz, 2 H), 6.89 (dd, J = 7.9, 1.5 Hz, 2 H), 3.92 (s, 6 H), 3.68 (s,
6 H).
13C NMR (CDCl3): d = 152.8 (C), 146.8 (C), 132.9 (C), 123.3 (CH),
123.2 (CH), 111.7 (CH), 60.6 (CH3), 55.8 (CH3).
found M+ 350.1530.
C22H22O4 (350.4)
calcd
found
C 75.41
75.83
H 6.33
6.44
2,2”’,3,3’”-Tetramethoxy-1,1’:4’,1”:4”,1’”-quaterphenyl (12)
Yield: 57%; yellow solid; mp 156 °C (CH2Cl2).
1H NMR (CDCl3): d = 7.72 (d, J = 8.1 Hz, 4 H), 7.66 (d, J = 8.1 Hz,
4 H), 7.14 (dd, J = 8.1, 7.8 Hz, 2 H), 7.02 (dd, J = 7.8, 1.6 Hz, 2 H),
6.95 (dd, J = 8.1, 1.6 Hz, 2 H), 3.93 (s, 6 H), 3.64 (s, 6 H).
13C NMR (CDCl3): d = 153.2 (C), 146.7 (C), 139.5 (C), 137.2 (C),
135.5 (C), 129.7 (CH), 126.7 (CH), 124.1 (CH), 122.6 (CH), 111.6
(CH), 60.7 (CH3), 56.0 (CH3).
IR (KBr): n = 2999, 2958, 1591, 1578, 1465, 1420, 1294, 1141,
1006, 764, 664 cm-1.
UV/vis (MeOH): l (e) = 204 (46000), 277 nm (3500).
MS: m/z (%) = 274 (14) [M]+, 138 (100).
HRMS (EI, 70 eV): C16H18O4 (274.3): m/z calcd: M 274.1205;
found M+ 274.1215.
IR (KBr): n = 2946, 2834, 1598, 1423, 1315, 1259, 1229, 1171,
C16H18O4 (274.3)
calcd
found
C 70.06
69.96
H 6.61
6.70
854, 788, 750, 641 cm-1.
UV/vis (MeOH/qualitative): l = 209, 287 nm.
MS: m/z (%) = 426 (100) [M]+.
1,1’-Biphenyl-2,2’,3,3’-tetrol (1)
The tetramethoxy derivative 8 (198 mg, 0.72 mmol) was dissolved
in CH2Cl2 (20 mL) and BBr3 (3.5 mL, 1 M in CH2Cl2) was added at
0 °C. The mixture was stirred overnight at r.t. and after addition of
MeOH (5 mL) the solvent was removed under vacuum. The residue
was dissolved in Et2O (30 mL), washed with H2O (3 × 30 mL),
dried (MgSO4) and the solvent was removed in vacuum; yield: 172
mg (quant); light brown solid; mp 214 °C (dec., Et2O).
1H NMR (CD3OD): d = 6.81 (dd, J = 7.5, 2.5 Hz, 2 H), 6.79 (t,
J = 7.5 Hz, 2 H), 6.76 (dd, J = 7.5, 2.5 Hz, 2 H).
13C NMR (CD3OD): d = 147.4 (C), 142.9 (C), 128.3 (C), 123.1
(CH), 121.6 (CH), 115.2 (CH).
HRMS (EI, 70 eV): C28H26O4 (426.5): m/z calcd: M 426.1831;
found M+ 426.1810.
C28H26O4 (426.5) calcd
found
C 78.85
78.28
H 6.14
6.18
2,2’,2”,3,3’,3”-Hexamethoxy-1,1’:4’,1”-terphenyl (14)
Yield: 28%; white solid; mp 126 °C (CH2Cl2).
1H NMR (CDCl3): d = 7.11 (t, J = 7.9 Hz, 2 H), 7.03 (s, 2 H), 6.95
(m, 4 H), 3.92 (s, 6 H), 3.72 (s, 6 H), 3.68 (s, 6 H).
13C NMR (CDCl3): d = 152.8 (C), 150.8 (C), 146.9 (C), 132.9 (C),
132.4 (C), 125.4 (CH), 123.5 (CH), 123.3 (CH), 111.7 (CH), 60.7
(CH3), 60.6 (CH3), 55.9 (CH3).
IR (KBr): n = 3454, 3328, 1622, 1595, 1465, 1374, 1217, 1072,
965, 746, 724 cm-1.
IR (KBr): n = 3444, 2962, 2837, 1601, 1476, 1399, 1269, 1225,
1140, 1010, 833, 785 cm-1.
UV/vis (MeOH): l (e) = 213 (37500), 249 (10800), 286 nm (4500).
MS: m/z (%) = 218 (100) [M]+.
UV/vis (MeOH): l (e) = 217 (62300), 249 nm (17100).
MS: m/z (%) = 410 (100) [M]+.
HRMS (EI, 70 eV): C12H10O4 (218.2): m/z calcd: M 218.0579;
found M+ 218.0570.
HRMS (EI, 70 eV): C24H26O6 (410.5): m/z calcd: M 410.1729;
found M+ 410.1749.
C12H10O4∑1/3 H2O (224.2) calcd
C 64.28 H 4.80
64.29 4.76
found
C24H26O6 (410.5) calcd
found
C 70.23
70.01
H 6.38
6.45
Suzuki Coupling of Dibromides 9, 11, and 13 with 2,3-
Dimethoxyphenylboronic Acid (6); General Procedure
The aryl dibromide (9, 11, or 138; 3.5 mmol) and Pd(PPh3)4 (0.17
mmol) were dissolved in toluene and 2 M aq Na2CO3 solution (3.5
mL) was added. Boronic acid 6 (2 equiv, 7 mmol dissolved in a
small amount of EtOH) was added and the mixture was heated to re-
flux overnight. After cooling to r.t. the solution was washed with
H2O, dried (MgSO4) and the solvent was removed in vacuum. The
crude product was purified by column chromatography (silica gel,
CH2Cl2).
1,1’:4’,1”-Terphenyl-2,2”,3,3”-tetrol (2)
Ether cleavage was performed as described for the preparation of 1.
Yield: 91%; yellow solid; mp 163 °C (Et2O).
1H NMR (CD3OD): d = 7.59 (s, 4 H), 6.82 (dd, J = 7.6, 2.0 Hz, 2 H),
6.79 (dd, J = 7.6, 2.0 Hz, 2 H), 6.76 (t, J = 7.6 Hz, 2 H).
13C NMR (CD3OD): d = 146.7 (C), 143.7 (C), 138.0 (C), 130.1 (C),
129.9 (CH) 122.3 (CH), 120.7 (CH), 115.0 (CH).
IR (KBr): n = 3491, 3328, 1616, 1470, 1357, 1301, 1262, 845, 779,
2,2”,3,3”-Tetramethoxy-1,1’:4’,1”-terphenyl (10)
Yield: 38%; yellow solid; mp 181-182 °C (CH2Cl2).
1H NMR (CDCl3): d = 7.62 (s, 4 H), 7.13 (t, J = 7.9 Hz, 2 H), 7.03
(dd, J = 7.9, 1.5 Hz, 2 H), 6.94 (dd, J = 7.9, 1.5 Hz, 2 H), 3.93 (s, 6
H), 3.64 (s, 6 H).
715 cm-1.
UV/vis (MeOH): l (e) = 203 (57900), 269 nm (24500).
MS: m/z (%) = 294 (100) [M]+.
HRMS (EI, 70 eV): C18H14O4 (294.3): m/z calcd: M 294.0892;
found M+ 294.0879.
Synthesis 2000, No. 11, 1557–1560 ISSN 0039-7881 © Thieme Stuttgart · New York

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M. Albrecht, M. Schneider
PAPER
C18H14O4 (294.3) calcd
found
C 73.46
73.02
H 4.79
4.76
13C NMR (CD3OD): d = 147.0 (C), 140.4 (C), 131.1 (C), 128.1 (C),
123.3 (CH), 116.0 (CH), 21.0 (CH3).
1,1’:4’,1”:4”,1’”-Quaterphenyl-2,2”’,3,3’”-tetrol (3)
Ether cleavage was performed as described for the preparation of 1.
IR (KBr): n = 3371, 2916, 1602, 1420, 1345, 1279, 1251,, 836, 734
cm-1.
Yield: quantitative; yellow solid; mp 264 °C (dec., Et2O).
UV-vis (MeOH): l (e) = 216 (35700), 252 (10100), 292 nm (4200).
MS: m/z (%) = 246 (100) [M]+.
1H NMR (CD3OD): d = 7.70 (d, J = 8.6 Hz, 4 H), 7.67 (d, J = 8.6
Hz, 4 H), 6.83 (dd, J = 7.5, 2.0 Hz, 2 H), 6.80 (dd, J = 7.5, 2.0 Hz,
2 H), 6.76 (t, J = 7.5 Hz, 2 H).
13C NMR (CD3OD): d = 146.7 (C), 143.8 (C), 140.4 (C), 139.2 (C),
130.8 (CH), 129.8 (C), 127.4 (CH), 122.2 (CH), 120.7 (CH), 115.1
(CH).
HRMS (EI, 70 eV): C14H14O4 (246.3): m/z calcd: M 246.0892;
found M+ 246.0887.
C14H14O4•1/3 H2O (252.26):
calcd
found
C 66.66 H 5.86
66.71 5.68
IR (KBr): n = 3535, 3481, 3034, 1622, 1498, 1470, 1344, 1268,
1244, 1003, 758, 736 cm-1.
Acknowledgement
UV/vis (MeOH): l (e) = 209 (79800), 289 nm (39600).
MS: m/z (%) = 370 (100) [M]+.
This work was supported by the Fonds der Chemischen Industrie
and the Deutsche Forschungsgemeinschaft.
HRMS (EI, 70 eV): C24H18O4 (370.4): m/z calcd: M 370.1205;
found M+ 370.1192.
References
C24H18O4•1/4 H2O (374.9) calcd
found
C 76.89
76.83
H 4.79
4.87
(1) (a) Scarrow, R. C.; White, D. L.; Raymond, K. N. J. Am.
Chem. Soc. 1985, 107, 6540.
(b) Lehn, J.-M.; Rigault, A.; Siegel, J.; Harrowfield, J.;
Chevrier, B.; Moras, D. Proc. Natl. Acad. Sci. USA 1987, 84,
2565.
1,1’:4’,1”-Terphenyl-2,2’,2”,3,3’,3”-hexol (4)
Ether cleavage was performed as described for the preparation of 1.
Yield: quantitative; beige solid; mp 273 °C (dec., Et2O).
1H NMR (CD3OD): d = 6.92 (s, 2 H), 6.83 (s, 6 H).
13C NMR (CD3OD): d = 142.2 (C), 143.8 (C), 143.0 (C), 128.0 (C),
127.1 (C), 123.7 (CH), 123.1 (CH), 121.6 (CH), 115.3 (CH).
(2) Reviews:
(a) Piguet, C.; Bernardinelli, G.; Hopfgartner, G. Chem. Rev.
1997, 97, 2005.
(b) Albrecht, M. Chem. Soc. Rev. 1998, 27, 281.
(3) (a) Baxter, P. N. W.; Lehn, J.-M.; Rissanen, K. Chem.
Commun. 1997, 1323.
(b) Kersting, B.; Meyer, M.; Rowers, R. E.; Raymond, K. N.
J. Am. Chem. Soc. 1996, 118, 7221.
(4) Preliminary communication:
Albrecht, M.; Schneider, M.; Fröhlich, R. New. J. Chem.
1998, 753.
(5) For the synthesis of linear oligo p-phenylene derivatives by
Suzuki coupling, see e.g.:
IR (KBr): n = 3892, 3310, 2925, 1624, 1500, 1447, 1445, 1377,
1361, 994, 801, 725 cm-1.
UV/vis (MeOH): l (e) = 219 (47300), 267 nm (24400).
MS: m/z (%) = 326 (100) [M]+.
HRMS (EI, 70 eV): C18H14O6 (326.31): m/z calcd: M 326.0790;
found M+ 326.0773.
C18H14O6•1/4 H2O (330.81):
calcd
found
C 65.35
65.51
H 4.42
4.65
(a) Rehahn, M.; Feast, W. J.; Wegner, G.; Schlüter, A.-D.
Polymer 1989, 30, 1060.
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(6) AM1 calculations: PC Spartan Plus, Wavefunction, Inc.
1997.
(7) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh,
M.; Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314.
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62, 2186.
(9) Albrecht, M. Synthesis 1996, 230.
(10) Margues, F. A.; Simonelli, F.; Oliveira, A. R. M.; Gohr, G. L.;
Leal, P.C. Tetrahedron Lett. 1998, 39, 943.
(11) Fukuyama, Y.; Asakawa, Y. J. J. Chem. Soc., Perkin Trans. 1
1991, 2737.
3,3’-Dimethoxy-5,5’-dimethyl-1,1’-biphenyl-2,2’-diol (16)
2-Methoxy-4-methylphenol (15; 414 mg, 3.00 mmol) was dis-
solved in CH2Cl2 (10 mL) and a CH2Cl2 solution of freshly prepared
methyltributylammonium permanganate (MTBAP)10 (480 mg, 1.50
mmol) was added at 0 °C. H2O (10 mL) was added after 15 min and
the mixture was stirred for further 10 min. The organic phase was
separated, dried (MgSO4) and solvent was removed in vacuum to
obtain crude 16 which was used without further purification; yield:
334 mg (81%); beige solid.
1H NMR (CDCl3): d = 6.82 (d, J = 1.8 Hz, 2 H), 6.71 (d, J = 1.8 Hz,
2 H), 3.98 (s, 6 H), 2.31 (s, 6 H).
5,5’-Dimethyl-1,1’-biphenyl-2,2’,3,3’-tetrol (5)
Ether cleavage was performed as described for the preparation of 1.
Yield: 92%; beige solid; mp 209 °C (dec., Et2O).
1H NMR (CD3OD): d = 6.65 (d, J = 1.6 Hz, 2 H), 6.58 (d, J = 1.6
Hz, 2 H), 2.24 (s, 6 H).
Article Identifier:
1437-210X,E;2000,0,11,1557,1560,ftx,en;H03800SS.pdf
Synthesis 2000, No. 11, 1557–1560 ISSN 0039-7881 © Thieme Stuttgart · New York