Preparation of phosphonoterephthalic acids via palladium-catalyzed coupling of aromatic iodoesters

Article abstract of DOI:10.1080/00397911.2012.673448

The current article reports in detail the preparation of two phosphonoterephthalic acids: 2-phosphonoterephthalic acid (1) and 2,5-diphosphonoterephthalic acid (2). Efficient, scalable syntheses have been developed for both compounds based on Pd-catalyzed

Full text of DOI:10.1080/00397911.2012.673448

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Preparation of Phosphonoterephthalic
Acids via Palladium-Catalyzed Coupling
of Aromatic Iodoesters
Nathaniel Ivan a , Vladimir Benin a & Alexander B. Morgan b
a Department of Chemistry, University of Dayton, Dayton, Ohio, USA
b Advanced Polymers Group, University of Dayton Research Institute,
Dayton, Ohio, USA
Accepted author version posted online: 04 Jan 2013.Version of
record first published: 04 Apr 2013.
To cite this article: Nathaniel Ivan , Vladimir Benin & Alexander B. Morgan (2013): Preparation of
Phosphonoterephthalic Acids via Palladium-Catalyzed Coupling of Aromatic Iodoesters, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:13, 1831-1836
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Synthetic Communications1, 43: 1831–1836, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2012.673448
PREPARATION OF PHOSPHONOTEREPHTHALIC ACIDS
VIA PALLADIUM-CATALYZED COUPLING OF
AROMATIC IODOESTERS
Nathaniel Ivan,1 Vladimir Benin,1 and Alexander B. Morgan2
1Department of Chemistry, University of Dayton, Dayton, Ohio, USA
2Advanced Polymers Group, University of Dayton Research Institute,
Dayton, Ohio, USA
GRAPHICAL ABSTRACT
Abstract The current article reports in detail the preparation of two phosphonoterephthalic
acids: 2-phosphonoterephthalic acid (1) and 2,5-diphosphonoterephthalic acid (2).
Efficient, scalable syntheses have been developed for both compounds based on Pd-
catalyzed coupling reactions of iodinated terephthalate esters. Phosphonoterephthalic acids
are potentially useful as flame-retardant additives or as monomers for the construction of
acid-pendant polymer chains.
Supplemental materials are available for this article. Go to the publisher’s online edition
of Synthetic Communications1 to view the free supplemental file.
Keywords Arenephosphonic acids; flame retardants; palladium-catalyzed coupling;
phosphonates; phosphonoterephthalic acids
INTRODUCTION
Phosphonic acids have been the subject of increasing interest in recent years. They
have been studied, both experimentally and theoretically,[1] for various applications,
such as protogenic groups in proton exchange membrance (PEM) separator materi-
als,[2,3] composite membranes,[4] and ologosiloxane-immobilized proton carriers.[5]
Phosphorous-based structures have found increasing use as both reactive and
additive flame retardants. Their share in the world flame-retardant market has been
gradually increasing, partly because of the steady reduction in use of halogenated
compounds, driven by environmental and health concerns. Phosphorous-based
Received October 4, 2011.
Address correspondence to Vladimir Benin, Department of Chemistry, University of Dayton,
Dayton, OH 45469-2367, USA. E-mail: vladimir.benin@notes.udayton.edu
1831

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N. IVAN, V. BENIN, AND A. B. MORGAN
structures act as flame retardants both in the vapor phase, by a radical mechanism
that interrupts the exothermic process and suppresses combustion, and in the
condensed phase, by promoting char formation.[6,7] Most of the phosphorus-based
structures that are commercially available are phosphate based, and while those
phosphates are easy to synthesize, they can have some hydrolytic instability and
durability problems when exposed to high humidity or recycling conditions.[8] There-
fore, there is a real need to develop new phosphorus-based flame retardants, which
have P-C bonds rather than P-O-C bonds. Further, the more phosphorus present in
a structure often translates into greater flame-retardant activity per unit weight.[9]
To that end, we have been studying the synthesis of new phosphorus-based flame
retardants with an emphasis on catalytic methods that may be industrially viable
vs. traditional molar reagent processes.
In a recent publication, we described the preparation of 2-phosphonoterephtha-
lic acid (1), through the intermediate formation of Grignard reagent (or organo-
lithium reagent) from 2-bromoxylene, which was subsequently reacted with diethyl
chlorophosphate, followed by oxidation and hydrolysis.[10] In an effort to avoid the
formation and use of organometallic intermediates, which demand inert conditions,
we have developed a palladium-catalyzed coupling approach, which has been
applied to the preparation of both the mono- and diphosphonoterephthalic acids
(compounds 1 and 2).
RESULTS AND DISCUSSION
The current report summarizes our efforts to develop a more general method
for the introduction of phosphonic ester=phosphonic acid unit(s) onto an aromatic
ring. The preparation of 1 has been described in two patent sources, following
two different methods.[11,12] Method 1 was based on the introduction of a phos-
phorus-containing moiety into the aromatic ring via aromatic electrophilic substi-
tution process involving p-xylene and thiophosphoryl trichloride, followed by acid
hydrolysis of the resultant 2,5-dimethylbenzenephosphonothioic dichloride and a
high-pressure Co-catalyzed oxidation in an autoclave of 2,5-dimethylphosphonic
acid.[11] Such a method is inherently complicated and difficult to apply in laboratory
conditions, because of the character of the necessary equipment. Method 2, on the
other hand, employed palladium- or nickel-catalyzed coupling of dimethyl 2-bromo-
terephthalate and triethyl phosphite, followed by acid hydrolysis.[12] Our repeated
attempts in the past, however, to reproduce the latter chemistry led invariably to full
recovery of the starting material. Consequently, several years ago, we developed and
published a protocol for the generation of 1 based on the conversion of bromo-p-
xylene into a Grignard (or organolithium) reagent, followed by reaction with diethyl-
chlorophosphate and a subsequent oxidation with KMnO4.[13] The inherent
drawbacks of such a method include incompatibility with certain functional groups,

PHOSPHONOTEREPHTHALIC ACIDS FROM IODOESTERS
1833
Scheme 1. Preparation of phosphonoterephthalic acid.
sensitive to Grignard or organolithium reagents, such carbonyl or ester groups, as
well as difficult polyfunctionalization (i.e., introduction of more than one phospho-
nate moiety), which would require the generation of di- or poly-Grignard reagent or
lithio derivative.
More recently, in our efforts to incorporate a phosphonate or boronate moiety
into an aromatic ring, we discovered that while transition-metal-catalyzed coupling
reactions of trialkyl or dialkyl phosphites with aromatic bromoesters did not
take place (as noted previously), the corresponding reactions with iodoesters
were quite facile. The reported preparations of compounds 1 and 2 are based on
the latter strategy.
Preparation of 2-Phosphonoterephthalic Acid (1)
The synthetic sequence employed in the preparation of compound 1 is shown in
Scheme 1. Dimethyl iodoterephthalate 3 was generated by diazotozation of dimethyl
2-aminoterephthalate, following a literature protocol,[14] followed by a reaction
with aqueous KI. Compound 3 was then reacted with excess trimethylphosphite,
in the presence of PdCl2, at elevated temperature, yielding the phosphonate ester
4.[12] The latter was successfully hydrolyzed to the target acid 1, using 3 M HCl at
80 ꢀC.
Scheme 2. Preparation of 2,5-diphosphonoterephthalic acid.

1834
N. IVAN, V. BENIN, AND A. B. MORGAN
Preparation of 2,5-Diphosphonoterephthalic Acid (2)
p-Xylene was diiodinated using periodic acid=iodine, in a mixture of acetic acid,
sulfuric acid, and water, to yield 2,5-diiodo-p-xylene 5 (Scheme 2).[15] Compound 5
was subjected to oxidation, using KMnO4 in a t-butanol=water solvent mixture, fol-
lowed by acidification, to yield 2,5-diiodoterephthalic acid 6. Attempts to conduct the
oxidation in purely aqueous medium were not successful, as they led to the partial
sublimation of 5 and consequently very poor yields of the acid 6. The published litera-
ture protocol suggested conversion of the diiodoacid 6 into the dimethyl ester 7 in a
two-step sequence, involving the intermediate generation of the diacid chloride. We
managed to accomplish the synthesis of 7 in a single step, employing Fischer esterifi-
cation of the acid 6 in excess methanol, with sulfuric acid as a catalyst. Compound 7
was then subjected to a reaction with trimethyl phosphite in the presence of PdCl2.
The resultant diphosphonic ester 8 was hydrolyzed in conditions analogous to the
ones described for the preparation of 1.
CONCLUSIONS
In this work we have reported the preparation and characterization of two
phosphonoterephthalic acids, compounds 1 and 2, using Pd-catalyzed coupling to
prepare the corresponding phosphonate esters. This protocol could be extended
further and utilized as a general methodology in the preparation of other aromatic
phosphonic acids, potentially useful as either flame retardants or for other chemical
research and synthetic needs.
EXPERIMENTAL
1H and 13C NMR 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; D2O: 4.76 ppm). 13C NMR spectra in D2O were indirectly referenced
to acetone-d6 in D2O (literature chemical shift value d 33.0 ppm for the CD3
signal).[16] Elemental analysis was provided by Atlantic Microlab, Norcross, GA.
Dimethyl aminoterephthalate was purchased from Acros Organics.
Preparation of Phosphonoterephthalic Esters (4, 8)
A mixture of iodoester (3 or 7) (1 eqv.), trimethyl phosphite (4 eqv. per iodine
site), and PdCl2 (0.1 eqv. per iodine site) was purged with nitrogen and then stirred
for 5 h at 150 ꢀC in a nitrogen atmosphere. Water and 1,2-dichloroethane were added
after cooling to ambient temperature. The organic layer was separated, washed two
times with water, and dried (MgSO4), and the volatile components were removed
under reduced pressure.
Dimethyl (dimethylphosphono)terephthalate (4)[12]. Purified on a silica-
gel column, using methylene chloride, followed by CH2Cl2–EtOAc ¼ 3:1, followed
1
by pure EtOAc. Colorless oil (81% yield). H NMR (CDCl3) d 3.83 (d, J ¼ 11.4 Hz,
6H), 3.96 (s, 3H), 3.97 (s, 3H), 7.79 (dd, J1 ¼ 4.9 Hz, J2 ¼ 8.0, 1H), 8.25 (dt,
J1 ¼ 1.5 Hz, J2 ¼ 8.0 Hz, 1H), 8.56 (dd, J1 ¼ 1.6 Hz, J2 ¼ 14.3 Hz, 1H).

PHOSPHONOTEREPHTHALIC ACIDS FROM IODOESTERS
1835
Dimethyl 2,5-bis(dimethylphosphono)terephthalate (8). Purified by
1
recrystallization from toluene. White solid (60% yield). Mp 129–131 ꢀC. H NMR
(CDCl3) d 3.84 (d, J ¼ 11.3 Hz, 12H), 3.98 (s, 6H), 8.28 (dd, J1 ¼ 13.5 Hz,
J2 ¼ 5.0 Hz, 2H); 13C NMR (CDCl3) d 53.3 (s), 53.5 (t, J ¼ 2.9 Hz), 131.2 (dd,
J1 ¼ 187.8 Hz, J2 ¼ 2.9 Hz), 134.4 (t, J ¼ 10.7 Hz), 137.9 (t, J ¼ 11.0 Hz), 166.7 (t,
J ¼ 3.1 Hz). Anal. calcd. for C14H20O10P2: C, 40.99; H, 4.91. Found: C, 41.12; H, 4.93.
Preparation of Phosphonoterephthalic Acids (1, 2)
The phosphonoterephthalate ester (4 or 8) (1.50 mmol) was suspended in
30 mL of 3 M HCl. The resultant mixture was stirred at 80 ꢀC for 24 h. The solution
was concentrated to dryness and tetrahydrofuran (THF) (10 mL) was added to the
solid. The resultant suspension was stirred for 10 min and vacuum filtered to yield
the product as a white solid.
2-Phosphonoterephthalic acid (1)[11–13]. Yield: 86%. Mp 296–298 ꢀC (lit.[12]
298 ꢀC). 1H 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, 1H).
1
2,5-Diphosphonoterephthalic acid (2). Yield: 95%. Mp 310 ꢀC (dec). H
NMR (D2O) d 8.27 (dd, J1 ¼ 13.0 Hz, J2 ¼ 5.0 Hz, 2H); 13C NMR (D2O, indirectly
referenced to acetione-d6 in D2O) d 136.0 (t, J ¼ 10.4 Hz), 137.6 (dd, J1 ¼ 176.2 Hz,
J2 ¼ 2.7 Hz), 139.4 (t, J ¼ 10.6 Hz), 173.5 (t, J ¼ 2.7 Hz). Anal. calcd. for
C8H8O10P2 ꢁ H2O: C, 27.92; H, 2.93. Found: C, 27.76; H, 3.17.
Complete experimental details are available online in the Supporting
Information.
ACKNOWLEDGMENTS
Funding for this project was provided by the National Institute of Standards
and Technology, Building and Fire Research Laboratory (NIST-BFRL), Fire
Research Grant No. 70NANB9H9183. Nathaniel Ivan thanks the Department of
Chemistry at the University of Dayton for summer financial support.
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