Preparation of some substituted terephthalic acids

Article abstract of DOI:10.1080/00397910600636675

We report in detail the preparation of two substituted terephthalic acids: 2-sulfomethylterephthalic acid (1) and 2-phosphonoterephthalic acid (2). Efficient, short syntheses have been developed for both compounds. They are potentially useful monomers for

Full text of DOI:10.1080/00397910600636675

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Preparation of Some Substituted Terephthalic
Acids
Susanna Branion a & Vladimir Benin a
a Department of Chemistry, University of Dayton, Dayton, Ohio, USA
Available online: 16 Feb 2007
To cite this article: Susanna Branion & Vladimir Benin (2006): Preparation of Some Substituted Terephthalic
Acids, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
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Synthetic Communicationsw, 36: 2121–2127, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600636675
Preparation of Some Substituted
Terephthalic Acids
Susanna Branion and Vladimir Benin
Department of Chemistry, University of Dayton, Dayton, Ohio, USA
Abstract: We report in detail the preparation of two substituted terephthalic acids:
2-sulfomethylterephthalic acid (1) and 2-phosphonoterephthalic acid (2). Efficient,
short syntheses have been developed for both compounds. They are potentially
useful monomers for construction of acid-pendant polymer chains.
Keywords: Acid-pendant polymers, arenephosphonic acids, arenesulfonic acids,
terephthalic acids
INTRODUCTION
Substituted terephthalic acids, with pendant acidic functional group, have
found increasing application in recent years. The best-known example
among them is 2-sulfoterephthalic acid, which has been employed in the prep-
aration of rigid-rod polymers,[1,2] polymers with enhanced solubility,[3]
dopants for electrically conductive polymers,[4] and enzyme inhibitors for
glaucoma treatment.[5]
Our recent attempts at preparation of sulfonic acid–pendant poly(benzimi-
dazole) (SPBI) demonstrated that conducting the polymerization at elevated
temperatures, necessary for satisfactory chain length, triggers an adverse
process of desulfonation and an accompanying loss of solubility of the
resultant polymer. Consequently, we focused our attention on the preparation
and employment of alternative acidic group–containing monomers. The
current report details our efforts to synthesize and characterize two particular
Received in the USA January 23, 2006
Address correspondence to Vladimir Benin, Department of Chemistry, University
of Dayton, 300 College Drive, Dayton, OH 45469-2357, USA. Tel.: 937-229-4762;
Fax: 937-229-2635; E-mail: vladimir.benin@notes.udayton.edu
2121

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S. Branion and V. Benin
compounds: 2-sulfomethylterephthalic acid (1) and 2-phosphonoterephthalic
acid (2) (Scheme 1). The former is a new compound, whose synthesis and
characterization we report for the first time, whereas 2-phosphonoterephthalic
acid has been previously reported in two patent sources from 1998.[6,7] For
reasons stated later, we found it necessary to develop a new synthetic
protocol for the preparation of 2, which is described in the current report.
RESULTS AND DISCUSSION
Preparation of 2-Sulfomethylterephthalic Acid (1)
The synthetic sequence employed in the preparation of compound 1 is shown
in Scheme 2. The challenge in the preparation of this material comes from the
fact that of the three C-atoms connected to the benzene ring, two are in the
form of carboxylic acid functional groups, and the third one is a benzylic
type carbon (i.e., the third center has a different degree of oxidation).
Therefore the carboxyl groups have to be introduced in the molecule as
such, rather than being generated at a later stage. The preparation starts,
therefore, with the dilithiation of 2,5-dibromotoluene with t-BuLi at –78 8C,
followed by reaction with dry ice and subsequent acidification, leading to
the introduction of the two carboxyl groups.[8] The resultant 2-methylter-
ephthalic acid (3) is esterified,[9] then side-chain brominated with NBS, to
produce dimethyl 2-bromomethylterephthalate (4).[9,10] Compound 4 is then
subjected to treatment with aqueous Na2SO3, in the presence of Bu4NBr as
catalyst, in a process of nucleophilic replacement of bromine by a sulfonate
anion.[11] The resultant sodium salt 5 is treated with conc. HCl to yield the
target acid 1.
Prepration of 2-Phosphonoterephtahlic Acid (2)
In previously published patent literature the preparation of 2 is described,
following two different methods. Method 1 relies on the introduction of a
phosphorus-containing moiety into the aromatic ring via aromatic electrophi-
lic substitution process involving p-xylene and thiophosphoryl trichloride,
Scheme 1.

Preparation of Some Substituted Terephthalic Acids
2123
Scheme 2.
followed by acid hydrolysis of the resultant 2,5-dimethylbenzenephospho-
nothioic dichloride and a high-pressure Co-catalyzed oxidation in an
autoclave of 2,5-dimethylphosphonic acid.[7] Such a method is inherently
complicated and difficult to apply in laboratory conditions, because of the
character of the necessary equipment. Method 2 employs palladium- or
nickel-catalyzed coupling of dimethyl 2-bromoterephthalate and triethyl
phosphite, followed by acid hydrolysis.[6] Our repeated attempts to
reproduce the latter chemistry led invariably to full recovery of the starting
material. Hence we undertook the development of a new synthetic
sequence, which would be easily applied in laboratory conditions, with repro-
ducible results. The synthesis is presented in Scheme 3 and is based on the
intermediate preparation of diethyl 2,5-dimethylbenzenephosphonate (6).
Earlier preparations of 6,[12,13] described in literature, rely on the introduction
of the phosphonate ester substructure via oxidative coupling of p-xylene with
triethylphosphite or diethylphosphite. This methodology, however, requires
substantial amounts of the relatively costly silver nitrate and also leads to gen-
eration of polyphosphonated species, as well as arene self-coupling by-
products. We found that compound 6 could be conveniently prepared from
2-bromo-p-xylene.[14] The latter can be either converted to the corresponding
Scheme 3.

2124
S. Branion and V. Benin
Grignard reagent (method A) or lithiated derivative (method B), followed
by reaction of the corresponding organometallic intermediate with diethyl
chlorophosphate. Compound 6, upon oxidation with KMnO4, yields the
dipotassium salt of 2-(diethylphosphonyl)terephthalic acid (7). Salt 7 is
treated with conc. HCl to yield the target compound 2.
CONCLUSIONS
In this work we have reported the preparation and characterization of two
2-substituted terephthalic acids, compounds 1 and 2, which are potentially
useful in the construction of functionalized polymer chains.
EXPERIMENTAL
1H and 13C spectra of intermediate and target compounds were recorded at
300 MHz and 75 MHz respectively and referenced to the solvent (CDCl3:
7.27 ppm and 77.0 ppm; DMSO-d6: 2.49 ppm and 39.5 ppm; D2O:
4.76 ppm). 31P NMR signals were indirectly referenced to 85% phosphoric
acid (d ¼ 0.0 ppm) via direct reference to P(OCH3)3 as an internal standard
(d ¼ þ141 ppm relative to 85% H3PO4). Elemental analysis was provided
by Atlantic Microlab, Norcross, GA. HRMS data was provided by the Mass
Spectrometry and Proteomics facility at the Ohio State University. 2,5-Dibro-
motoluene was purchased from the Aldrich Chemical Co. Compounds 3 and 4
were prepared following previously published procedures.[9] Compound 6,
although previously reported,[12,13] was prepared following a new approach.
Hence its synthesis and spectral data are reported in detail.
2-(Sulfomethyl)terephthalic Acid (1)
An aqueous solution of tetrabutylammonium bromide (0.008 g, 0.025 mmol
in 4 mL of water) was added to a round-bottom flask containing dimethyl
2-bromomethylterephthalate (0.28 g, 0.98 mmol), Na2SO3 (0.15 g,
1.15 mmol), and ethanol (4 mL). The resultant mixture was stirred at reflux
for 12 h and cooled to ambient temperature, and the solvent was removed
under reduced pressure. Methylene chloride (10 mL) was added to the
residual solid; the mixture was stirred for 15 min and then vacuum filtered.
The solid was washed with methylene chloride and dried to yield the
sodium salt 5 as white crystalline compound (0.20 g, 67%). 1H NMR
(D2O) d 3.90 (s, 3H), 3.91 (s, 3H), 4.64 (s, 2H), 7.89 (d, J ¼ 8.8 Hz, 1H),
8.01–8.04 (m, 2H). Sodium salt 5 (0.20 g, 0.64 mmol) was added to
4.0 mL of concentrated hydrochloric acid, and the resultant mixture was
stirred at reflux for 12 h. The mixture was then cooled to ambient

Preparation of Some Substituted Terephthalic Acids
2125
temperature and left in a refrigerator for 18 h. The solid was vacuum filtered
and dried in a drying pistol (60 8C at 1 mm Hg for 12 h) to yield 0.17 g (98%)
of acid 1. Mp 290–292 8C. 1H NMR (D2O) d 4.66 (s, 2H), 7.91
(d, J ¼ 8.0 Hz, 1H), 8.00–8.04 (m, 2H); 1H NMR (DMSO-d6) d 4.26
(s, 2H), 7.72 (d, J ¼ 8.1 Hz, 1H), 7.84 (dd, J1 ¼ 8.1 Hz, J2 ¼ 1.8 Hz, 1H),
7.97 (d, J ¼ 1.8 Hz, 1H); 13C NMR (DMSO-d6) d 54.1, 127.2, 129.6,
132.2, 133.4, 134.7, 136.7, 166.8, 168.6. HRMS (FABþ) m/z calcd. for
C9H8O7S [M þ Na]þ 282.9888, found 282.9893. Anal. calcd. for
.
C9H8O7S H2O: C, 38.85; H, 3.62; S, 11.52. Found: C, 38.71; H, 3.72;
S, 11.38.
Diethyl 2,5-Dimethylbenzenephosphonate (6)
Method A
A suspension of Mg (1.42 g, 58.42 mmol) in anhydrous THF (100 mL) was
brought to reflux. Several drops of 1,2-dibromoethane were added, followed
by dropwise addition of 2-bromo-p-xylene (9.01 g, 48.68 mmol, 6.72 mL) at
a rate to maintain reflux of the reaction mixture. When the addition was
complete, the mixture was stirred for additional 1 h at 60 8C, cooled to
ambient temperature, and added dropwise to a stirred solution of diethyl chlor-
ophosphate (8.40 g, 48.68 mmol, 7.00 mL) in anhydrous THF (20 mL) at 0 8C.
The resultant mixture was stirred at ambient temperature for 1 h, followed by
12 h at 60 8C. It was then poured into an aqueous solution of NH4Cl, and the
organic layer was separated. The aqueous fraction was saturated with NaCl,
and the organic layer was separated. The combined organic fraction was
dried (MgSO4), the solvent removed under reduced pressure, and the
residue passed through a short silica-gel column, which was eluted succes-
sively with hexane–CH2Cl2 ¼ 1 : 1 (400 mL), hexane–EtOAc ¼ 1 : 3
(400 mL), and EtOAc (200 mL). The second and third fractions were
combined, and the solvent was removed under reduced pressure to yield the
target as a colorless oil (7.10 g, 60%). 1H NMR (CDCl3) d 1.32
(t, J ¼ 7.5 Hz, 6H), 2.34 (s, 3H), 2.52 (s, 3H), 4.02–4.19 (m, 4H), 7.14 (dd,
J1 ¼ 7.7 Hz, J2 ¼ 5.9 Hz, 1H), 7.23 (d, J ¼ 7.7 Hz, 1H), 7.75 (dd,
J1 ¼ 14.7 Hz, J2 ¼ 1.6 Hz, 1H); 13C NMR (CDCl3) d 16.3 (d, J ¼ 6.5 Hz),
20.6 (d, J ¼ 3.4 Hz), 20.7 (s), 61.8 (d, J ¼ 5.4 Hz), 126.4 (d, J ¼ 182.6 Hz),
131.1 (d, J ¼ 15.8 Hz), 133.1 (d, J ¼ 3.2 Hz), 134.5 (d, J ¼ 10.5 Hz), 134.9
(d, J ¼ 15.0 Hz), 138.5 (d, J ¼ 9.9 Hz); 31P NMR (proton-decoupled)
(CDCl3) d 19.9 (s).
Method B
t-BuLi (10.80 mmol, 6.36 mL of 1.7 M soln. in pentane) was added dropwise
to a solution of 2-bromo-p-xylene (2.00 g, 10.80 mmol, 1.50 mL) in anhydrous

2126
S. Branion and V. Benin
THF (10 mL) at –78 8C (dry ice–acetone) in inert atmosphere. The reaction
mixture was stirred for one hour at –78 8C then gradually warmed up to 0 8C
over a 0.5 h period. The resultant solution was added dropwise to a solution of
diethyl chlorophosphate (1.86 g, 10.80 mmol, 1.55 mL) in anhydrous THF
(5 mL) at 0 8C, and stirring was continued for 12 h at ambient temperature.
The resultant mixture was added to an aqueous solution of ammonium
chloride (2.00 g in 50 mL of water) followed by addition of ether (50 mL).
After stirring for 5 min, the layers were separated, the organic layer was
dried (MgSO4), and the solvent removed under reduced pressure. The crude
product was further purified on a silica-gel column (hexane–ethyl
acetate ¼ 1 : 1). The solvents were removed to yield the product as a clear
oil (2.05 g, 78%). Spectral data of the product were analogous to those
reported under method A.
2-Phosphonoterephthalic Acid (2)
A mixture of compound 6 (5.40 g, 22.31 mmol), water (90 mL), and t-butanol
(10 mL) was heated to reflux. Potassium permanganate (14.00 g, 89.16 mmol)
was added in small portions, and the mixture was left stirring at reflux for 2 h.
The temperature was then reduced to 80 8C, and stirring continued for 12 h.
The mixture was then cooled to ambient temperature and vacuum filtered
on a fritted funnel. The filtrate was concentrated under reduced pressure and
then acidified with concentrated hydrochloric acid, while controlling the
temperature with an ice bath. The mixture was kept for an additional 3 h at
0 8C, and the resultant precipitate was vacuum filtered. It was then
suspended in water (10 mL), heated to reflux, cooled, vacuum filtered, and
dried to yield 3.33 g (61%) of white solid. Mp 295–297 8C (lit.[6,7] 298 8C,
1
288–290 8C). H NMR (D2O) d 7.67 (dd, J1 ¼ 8.0 Hz, J2 ¼ 4.0 Hz, 1H),
7.93 (dt, J1 ¼ 8.0 Hz, J2 ¼ 1.0 Hz, 1H), 8.27 (dd, J1 ¼ 15.0 Hz, J2 ¼ 1.0 Hz,
1
1H); H NMR (DMSO-d6) d 7.87 (dd, J1 ¼ 8.1 Hz, J2 ¼ 4.8 Hz, 1H), 8.02
(dt, J1 ¼ 8.1 Hz, J2 ¼ 1.5 Hz, 1H), 8.42 (dd, J1 ¼ 13.8 Hz, J2 ¼ 1.5 Hz, 1H);
13C NMR (DMSO-d6) d 130.8 (d, J ¼ 11.6 Hz), 131.5 (s), 132.3
(d, J ¼ 12.5 Hz), 133.6 (d, J ¼ 12.1 Hz), 135.9 (s), 140.2 (d, J ¼ 9.0 Hz),
167.0 (s), 169.4 (d, J ¼ 5.0 Hz); 31P NMR (proton-decoupled) (DMSO-d6) d
10.8 (s). Anal. calcd. for C8H7O7P: C, 39.04; H, 2.87. Found: C, 39.31;
H, 3.08.
ACKNOWLEDGMENTS
Partial funding for this project was provided by a Challenge Grant from the
Ohio Board of Regents. S. Branion thanks the University of Dayton
Research Council for summer financial support.

Preparation of Some Substituted Terephthalic Acids
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