Synthesis of rigid polyaromatic dialdehydes

Article abstract of DOI:10.1081/SCC-200048397

Rigid polyaromatic dialdehydes: biphenyl-4,4′-dialdehyde and its longer analogues have been synthesized in high yields by using the Suzuki-Miyaura cross-coupling reaction. In addition, a novel procedure for a gram-scale preparation of biphenyl-4,4′-dicarbaldehyde from commercially available 4,4′-bis(chloromethyl)biphenyl has been developed.

Full text of DOI:10.1081/SCC-200048397

This article was downloaded by: [Umeå University Library]
On: 12 November 2014, At: 14:46
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of Rigid Polyaromatic
Dialdehydes
Michala Kozáková a , Miloš Buděšínský a & Jana
Hodačová a
a Institute of Organic Chemistry and Biochemistry ,
Flemingovo nám. 2, 166 10, Prague 6, Czech
Republic
Published online: 28 Jul 2007.
To cite this article: Michala Kozáková , Miloš Buděšínský & Jana Hodačová (2005)
Synthesis of Rigid Polyaromatic Dialdehydes, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 35:2,
161-167, DOI: 10.1081/SCC-200048397
To link to this article: http://dx.doi.org/10.1081/SCC-200048397
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any
losses, actions, claims, proceedings, demands, costs, expenses, damages,

and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communicationsw, 35: 161–167, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200048397
Synthesis of Rigid
Polyaromatic Dialdehydes
´
´
ˇ
ˇˇ´
´
ˇ
´
Michala Kozakova, Milos Budesınsky, and Jana Hodacova
Institute of Organic Chemistry and Biochemistry,
Prague, Czech Republic
Abstract: Rigid polyaromatic dialdehydes: biphenyl-4,40-dialdehyde and its longer
analogues have been synthesized in high yields by using the Suzuki–Miyaura cross-
coupling reaction. In addition, a novel procedure for a gram-scale preparation of
biphenyl-4,40-dicarbaldehyde from commercially available 4,40-bis(chloromethyl)bi-
phenyl has been developed.
Keywords: Rigid dialdehydes, Suzuki–Miyaura cross-coupling, terphenyl derivatives
INTRODUCTION
Rigid rodlike aromatic dialdehydes are important synthetic building blocks in
construction of large macrocycles, several types of supramolecular arrays, as
well as novel materials for electronics. The Suzuki–Miyaura cross-coupling
reaction[1] produces a series of polyphenyl aromatic dialdehydes while the
length of the molecule and its substitution can be systematically varied. We
present here several examples showing that polyphenyl dialdehydes can be
obtained in excellent yields by using this synthetic approach. Under the con-
ditions typical for the Suzuki–Miyaura cross-coupling reaction, (i.e., using
Pd(PPh3)4 as a catalyst and 1,2-dimethoxyethane as a solvent), biphenyl-
4,40-dicarbaldehyde 1 and three [1,10:40,100]terphenyl-4,400-dicarbaldehydes
2–4 were synthesized on the reaction of 4-formylphenylboronic acid with
Received in Poland October 21, 2004
Address correspondence to Jana Hodacova, Institute of Organic Chemistry and
ˇ
´
´
Biochemistry, Flemingovo nam. 2, 166 10, Prague 6, Czech Republic. E-mail:
hodacova@uochb.cas.cz

´ ´ ˇˇ´ ˇ ´
´
M. Kozakova, M. Budesınsky, and J. Hodacova
162
the corresponding aryl bromides in yields higher than 90% (Scheme 1). In the
attempt to prepare the longer analogue, [100,10:40,100:400,100]quaterphenyl-4,4000-
dicarbaldehyde, from 4,40-dibromobiphenyl and 4-formylphenylboronic
acid, the insoluble material was obtained.
Previously, several synthetic approaches to dialdehyde 1 have been
published. They use either the direct formylation of biphenyl,[2,3] the func-
tional group transformations of 4,40-disubstituted biphenyls,[4–8] or the
homo-coupling reactions of 4-chloro- or 4-bromo-benzaldehyde.[9–16] When
we were searching for a preparative method, only two procedures seemed to
be suitable for a practical gram-scale preparation of 1. The first is based on
the reaction of 4,40-dibromobiphenyl with n-butyllithium followed by
dimethylformamide giving 1 in 60% yield.[6,7] The second one uses the
reaction of 4,40-bis(bromomethyl)biphenyl with dimethylsulfoxide in the
presence of NaHCO3 producing dialdehyde 1 in 50% yield.[4] We have
developed an alternative preparative procedure based on the transformation
of 4,40-bis(chloromethyl)biphenyl (5), which is commercially available and
cheap, to 4,40-bis(hydroxymethyl)biphenyl (7) and its oxidation using pyridi-
nium chlorochromate (Scheme 2).
Attempt at the direct hydrolysis of 5 to 7 has been unsuccessful due to
insolubility of 5 in aqueous solution. For that reason, we transformed 5 to
acetate 6, whose hydrolysis processed smoothly.[17] The pyridinium chloro-
chromate oxidation of 7 gave 1 repeatedly in 75–90% yield. The reaction
does not require any special equipment and is fast enough. After the
reaction, the colored chromium-based compounds are removed by passing
the crude product through a silica gel column but no real chromatography
(i.e., fraction separation) is needed.
It is surprising that only little attention has been paid to the synthesis of
dialdehyde 2 in the past. It has been obtained from 4,40-bis(bromo-
methyl)[1,10:40,100]terphenyl either by Sommelet reaction in 47% yield[18,19]
or on the reaction with dimethylsulfoxide in the presence of NaHCO3 in
Scheme 1. Synthesis of dialdehydes 1–4 by Suzuki–Miyaura cross-coupling.

Synthesis of Rigid Polyaromatic Dialdehydes
163
Scheme 2. Preparative synthesis of 1.
28% yield.[4] We demonstrate here that the Suzuki–Miyaura cross-coupling is
superior over the previous synthetic methods. Moreover, substituents can be
easily introduced into the terphenyl skeleton by means of this synthetic
approach as it is shown on the syntheses of novel dialdehydes 3 and 4.
EXPERIMENTAL
The reactions were monitored by TLC on aluminium sheets coated with Silica
gel 60 F254 (Merck) using the UV detection. Preparative chromatographic sep-
arations were performed on Silica gel 60, 63–200 mm (Fluka). Melting points
were determined on a Kofler block and are uncorrected. The NMR spectra
were measured on a Bruker 500 instrument (1H at 500.13 MHz, 13C at
125.77 MHz) in CDCl3 or in d6-dimethylsulfoxide (d6-DMSO). The
chemical shifts are reported in ppm and are referenced to an internal tetra-
methylsilane (TMS) standard (dH ¼ 0 ppm) or to the signal of solvent
(CDCl3: dC ¼ 77.0 ppm; DMSO: dH ¼ 2.5 and dC ¼ 39.7 ppm). Coupling
constants J are given in Hz. Structural assignment of proton signals is based
on characteristic chemical shifts, multiplicity, and the intensity of individual
signals. Elemental analyses were performed on a Perkin–Elmer 2400
analyzer. Mass spectra were recorded on a ZAB-EQ (VG Analytical) instru-
ment using the electron impact ionization (70 eV) technique. Chemicals
were purchased from Aldrich and were used without further purification.
1,4-Dibromo-2,3,5,6-tetramethylbenzene[20] and 1,4-dibromo-2,3,5,6-tetra-
kis(methoxymethyl)benzene[21] were prepared according to the literature
procedures.
General Procedure for the Suzuki–Miyaura Cross-coupling
A solution of 4-formylphenylboronic acid (1.0 or 2.0 mmol) and arylbromide
or aryldibromide (1.0 mmol) in 1,2-dimethoxyethane (25 mL) was purged

´ ´ ˇˇ´ ˇ ´
´
M. Kozakova, M. Budesınsky, and J. Hodacova
164
with argon, and the reaction was carried out under the argon atmosphere.
Catalytic amount of Pd(PPh3)4 (50 mmol) and a solution of K2CO3 (6 mmol)
in water (2.5 mL) were added, and the mixture was refluxed for 6 h. After
cooling down to room temperature, the solvent was evaporated, and the
residue was subjected to column chromatography.
Biphenyl-4,40-dicarbaldehyde (1)
Prepared from 4-bromobenzaldehyde (0.14 g; 0.76 mmol). Chromatography
elution: toluene–ethyl acetate (from 0 to 10%). Yield 0.15 g (94%). M. p.
140–1428C. For C14H10O2 (210.23) calculated: 79.98% C, 4.79% H; found:
1
79.82% C, 4.77% H. H NMR (CDCl3): 7.81 m, 4H (H-2, 20, 6, 60); 8.01 m,
13
4H (H-3, 30, 5, 50); 10.09 s, 2H (2x CH55O). C NMR: 128.02 (C-2, 20, 6,
60); 130.36 (C-3, 30, 5, 50); 135.97 (C-1, 10); 145.55 (C-4, 40); 191.71 (2x
CH55O). MS: 210 (Mþ, 100%), 181 (8%), 152 (46%), 76 (12%).
[1,10:40,100]Terphenyl-4,400-dicarbaldehyde (2)
Prepared from 1,4-dibromobenzene (0.58 g; 2.45 mmol). White crystals were
formed in the course of the reaction. They were filtered, washed twice with
diethyl ether, and dried. Sample for analysis was crystallized from ethanol.
Yield 0.67 g (96%). M. p. 211–2138C. For C20H14O2 (286.32) calculated:
1
83.90% C, 4.93% H; found: 83.48% C, 4.92% H. H NMR (CDCl3): 7.77 s,
4H (H-20, 30, 50, 60); 7.82 m, 4H (H-2, 6, 200, 600); 7.99 m, 4H (H-3, 5, 300,
13
500); 10.08 s, 2H (2x CH55O). C NMR (CDCl3): 127.60 (C-2, 6, 200, 600);
127.97 (C-20, 30, 50, 60); 130.35 (C-3, 5, 300, 500); 135.46 (C-þ4, 400); 139.76
(C-10, 40); 146.23 (C-1, 100); 191.79 (2x CH55O). MS: 286 (M ; 100%), 228
(17%), 202 (6%), 142 (7%), 101 (8%), 57 (14%), 43 (14%).
20,30,50,60-Tetramethyl-[1,10:40,100]terphenyl-4,400-dicarbaldehyde (3)
Prepared from 1,4-dibromo-2,3,5,6-tetramethylbenzene[20] (0.19 g; 0.65
mmol). Chromatography elution: hexane-toluene (from 30 to 50%). Yield
0.20 g (91%). M. p. 248–2518C. For C24H22O2 (342.43) calculated: 84.18%
1
C, 6.48% H; found: 83.94% C, 6.32% H. H NMR (CDCl3): 1.94 s, 12H
(4x CH3); 7.37 m, 4H (H-2, 6, 200, 600); 7.98 m, 4H (H-3, 5, 300, 500); 10.10 s,
13
2H (2x CH55O). C NMR (CDCl3): 17.99 (4x CH3); 129.85 (C-3, 5, 300,
500); 130.24 (C-2, 6, 200, 600); 131.53 (C-20, 30, 50, 60); 134.94 (C-4, 40þ0);
140.53 (C-10, 40); 149.47 (C-1, 100); 192.00 (2x CH55O). MS: 342 (M ;
100%), 283 (10%), 253 (11%), 239 (10%), 115 (12%), 91 (19%), 85 (24%),
83 (38%).

Synthesis of Rigid Polyaromatic Dialdehydes
165
20,30,50,60-Tetrakis(methoxymethyl)[1,10:40,100]terphenyl-4,400-
dicarbaldehyde (4)
Prepared from 1,4-dibromo-2,3,5,6-tetrakis(methoxymethyl)benzene[21]
(0.13 g; 0.32 mmol). Chromatography elution: toluene–ethyl acetate (from 5
to 20%). Yield 0.14 g (93%). M. p. 128–1308C. For C28H30O6 (462.53) calcu-
1
lated: 72.71% C, 6.54% H; found: 72.51% C, 6.44% H. H NMR (CDCl3):
3.13 s, 12H (4x OCH3); 4.13 s, 8H (4x CH2O); 7.54 m, 4H (H-2, 6, 200, 600);
7.97 m, 4H (H-3, 5, 300, 500); 10.13 s, 2H (2x CH55O). 13C NMR (CDCl3):
58.43 (4x OCH3); 69.00 (4x CH2O); 128.85 (C-3, 5, 300, 500); 130.74 (C-2, 6,
200, 600); 135.35 (C-4, 400); 135.79 (C-20, 30, 50, 60); 143.84 (C-10, 40); 145.74
(C-1, 100); 192.13 (2x CH55O). MS: 462 (Mþ; 100%), 430 (95%), 326
(58%), 265 (32%), 105 (20%), 75 (46%), 45 (67%).
Preparative Procedure for Synthesis of 1
4,40-Bis(acetoxymethyl)biphenyl[17] (6)
To a solution of 4,40-bis(chloromethyl)biphenyl (13.29 g; 52.9 mmol) in
glacial acetic acid (150 mL) sodium acetate (16.40 g; 0.20 mol) was added,
and the resulting mixture was refluxed for 16 h. After cooling, it was poured
into water and stirred for 30 mins. White precipitate was filtered, washed
with water, and dried. The crude product was crystallized from diisopropyl
ether to yield 11.67 g (74%) of 6. M. p. 83–868C. For C18H18O4 (298.33) cal-
culated: 72.47% C, 6.08% H; found: 72.36% C, 6.14% H. 1H NMR (CDCl3):
2.12 s, 6H (2x CH3); 5.15 s, 4H (2x CH2O); 7.44 m, 4H (H-2, 20, 6, 60); 7.58 m,
4H (H-3, 30, 5, 50).13C NMR: 21.03 (2x CH3); 66.01 (2x CH2O); 127.70 (C-2,
20, 6, 60); 128.81 (C-3, 30, 5, 50); 135.13 (C-4, 40); 140.67 (C-1, 10); 170.90 (2x
C55O). MS: 298 (Mþ; 100%), 256 (17%), 239 (59%), 196 (10%), 178 (40%),
165 (27%), 149 (9%).
4,40-Bis(hydroxymethyl)biphenyl (7)
To a solution of 6 (11.67 g; 39.1 mmol) in methanol (220 mL) an aqueous
KOH was added (15.14 g; 0.27 mol; 60 mL), and the mixture was refluxed
for 8 h. After cooling to room temperature, the mixture was poured into
water and neutralized with diluted HCl. The precipitate was filtered, washed
with diethyl ether, and dried. Yield 8.07 g (96%). M. p. 190–1928C. For
C14H14O2 (214.26) calculated: 78.48% C, 6.59% H; found: 78.03% C,
1
6.16% H. H NMR (DMSO-d6): 4.53 d, 4H (2x CH2O); 5.20 t, 2H (2x
OH); 7.39 m, 4H (H-2, 20, 6, 60); 7.61 m, 4H (H-3, 30, 5, 50). 13C NMR
(CDCl3): 68.46 (2x CH2O); 127.35 (C-2, 6, 20, 60); 127.97 (C-3, 5, 30, 50);

´ ´ ˇˇ´ ˇ ´
´
M. Kozakova, M. Budesınsky, and J. Hodacova
166
136.47 (C-1, 10); 138.79 (C-4, 40). MS: 214 (Mþ; 100%), 197 (24%), 183
(20%), 165 (26%), 155 (78%), 77 (28%).
Biphenyl-4,40-dicarbaldehyde (1)
To a solution of pyridinium chlorochromate (32.47 g; 0.15 mol) in dichloro-
methane (70 mL) a solution of 7 (8.07 g; 37.7 mmol) in dichloromethane
(150 mL) was added, and the mixture was stirred for 2 hr at room temperature.
Solid was filtered off and washed with diethyl ether. The filtrates were
combined and the solvent removed. The residue was passed through a short
silica gel column in ethyl acetate to remove chromium salts. Upon the
solvent removal, 1 was obtained in 79% yield (6.25 g). M. p. 139–1418C.
For C14H10O2 (210.23) calculated: 79.98% C, 4.79% H; found: 79.58% C,
4.99% H. Spectra were identical with those given above.
ACKNOWLEDGMENTS
Financial support from the Academy of Sciences (project Z4 055 905) and
Grant Agency of the Czech Republic (203/03/0087) is gratefully
acknowledged.
REFERENCES
1. Suzuki, A.; Miyaura, N. Palladium-catalyzed cross-coupling reactions of organo-
boron compounds. Chem. Rev. 1995, 95, 2457–2483.
2. Hinkel, L. E.; Ayling, E. E.; Beynon, J. H. Studies on hydrogen cyanide. Part VII.
Aldehydes from aromatic hydrocarbons. J. Chem. Soc. 1936, 339–346.
3. Tanaka, M.; Fujiwara, M.; Ando, H.; Souma, Y. Synthesis of polynuclear aromatic
dialdehydes in HF-SbF5. J. Org. Chem. 1993, 58, 3213–3215.
4. Helms, A.; Heiler, D.; McLendon, G. Electron transfer in bis-porphyrin donor-
acceptor compounds with polyphenylene spacers shows a weak distance depen-
dence. J. Am. Chem. Soc. 1992, 114, 6227–6238.
5. Rossi, S.; Pirola, P.; Groppetti, A.; Zappia, M. L.; Maggi, R. Quaternary salts of
bis(O-dialkylaminoalkyl)dioximes with curariform activity. Farmaco Ed. Sci.
1966, 21, 751–774.
6. Shabtai, E.; Segev, O.; Beust, R.; Rabinovitz, M. Charged paracyclophanes behave
as annulenes with enhanced anisotropy. J. Chem. Soc. Perkin Trans. 2 2000,
1233–1241.
¨
7. Thulin, B.; Wennerstrom, O.; Somfai, I.; Chmielarz, B. A new synthesis of
[2.2.2.2]cyclophanetetraenes. Acta Chem. Scand., Ser. B 1977, 31, 135–140.
8. Ullmann, F.; Meyer, G. M.; Loewenthal, O.; Gilli, E. Ueber symmetrische Biphe-
nylderivate. Justus Liebigs Ann. Chem. 1904, 332, 38–81.
9. Colon, I.; Kelsey, D. R. Coupling of aryl chlorides by nickel and reducing metals.
J. Org. Chem. 1986, 51, 2627–2637.

Synthesis of Rigid Polyaromatic Dialdehydes
167
10. Howarth, J.; James, P.; Dai, J. The coupling of aryl halides in the ionic liquid
[bmim]PF6. Tetrahedron Lett. 2000, 41, 10319–10321.
11. Iyoda, M.; Otsuka, H.; Sato, K.; Nisato, N.; Oda, M. Homocoupling of aryl halides
using nickel(II) complex and zinc in the presence of Et4NI. An efficient method for
the synthesis of biaryls and bipyridines. Bull. Chem. Soc. Jpn. 1990, 63, 80–87.
12. Kuroboshi, M.; Waki, Y.; Tanaka, H. Palladium-catalyzed tetrakis(dimethyl-
amino)ethylene-promoted reductive coupling of aryl halides. J. Org. Chem.
2003, 68, 3938–3942.
13. Leadbeater, N. E.; Resouly, S. M. The use of Ni(CO)2(PPh3)2 in aryl and pyridyl
coupling reactions. Tetrahedron Lett. 1999, 40, 4243–4246.
14. Qafisheh, N.; Mukhopadhyay, S.; Sasson, Y. Highly selective Pd-catalyzed
reductive coupling of substituted haloarenes with supported phase-transfer
catalyst using Zn as the reducing agent. Adv. Synth. Catal. 2002, 344, 1079–1083.
15. Semmelhack, M. F.; Helquist, P.; Jones, L. D.; Keller, L.; Mendelson, L.;
Ryono, L. S.; Smith, J. G.; Stauffer, R. D. Reaction of aryl and vinyl halides
with zerovalent nickel—preparative aspects and the synthesis of alnusone.
J. Am. Chem. Soc. 1981, 103, 6460–6471.
16. Shirakawa, E.; Murota, Y.; Nakao, Y.; Hiyama, T. Homocoupling of organo-
stannanes catalyzed by iminophosphine-palladium. Synlett 1997, 1143–1144.
17. Reynolds, D. D.; Dunham, K. R. Polycarbonates from 4,40-Bis(hydroxymethyl)bi-
phenyl Bis(alkyl or aryl carbonates). US Patent 2,789,969, April 23, 1957.
18. Drefahl, G.; Thalman, K. p-Terphenyl derivatives. J. Prakt. Chem. 1963, 20,
56–61.
¨
19. Wulff, G.; Lauer, M.; Disse, B. Uber die synthese von monomeren zur einfu¨hrung
von aminogruppen in polymere in definiertem Abstand. Chem. Ber. 1979, 112,
2854–2865.
20. Sohmiya, H.; Kimura, T.; Fujita, M.; Ando, T. Solid-state organic reactions pro-
ceeding by pulverization: oxidation and halogenation with Iodosobenzene and
inorganic solid-supports. Tetrahedron 1998, 54, 13737–13750.
¨
¨ ¨
21. Hopff, H.; Doswald, P.; Manukian, B. K. Uber pyromellitsaure- und cumidinsaure-
derivate. Helv. Chim. Acta 1961, 44, 1231–1237.