Synthesis and reactivity of (benzoxazol-2-ylmethyl)phosphonic acid

Article abstract of DOI:10.1021/ic101079b

An efficient three step synthesis of (benzoxazol-2-ylmethyl)phosphonic acid (6-H₂) is described along with IR, mass spectrometry (MS), and ¹H, ¹³C, and ³¹P NMR spectroscopic characterization data, and a single crystal X-ray diffraction structure determination. 6-H₂ is unstable in acidic aqueous solutions (pH < 4) undergoing ring-opening to give [(2-hydroxyphenylcarbamoyl)methyl] phosphonic acid (7-H₂) that is characterized by IR, MS, and NMR methods. The protonation constants (pK_a) for 7-H₂ have been measured, and crystal structure determinations for (NH₄)(7-H) and K(7-H) · DMF are described. Reactions of NaOH and KOH with 6-H₂ in MeOH/H₂O solutions led to isolation and crystal structure determinations of the salts [Na(6-H) · H₂O]₂, K(6-H), Na₃(6)(6-H) · H₂O, and [K ₂(6)]₂ · 3H₂O. The complexation reactions of 7-H₂ with La(III), Nd(III), and Gd(III), as a function of pH, were also examined by titrametric methods, and a model for the 1:1 anion binding with Ln(III) cations is proposed.

Full text of DOI:10.1021/ic101079b

Inorg. Chem. 2010, 49, 9369–9379 9369
DOI: 10.1021/ic101079b
Synthesis and Reactivity of (Benzoxazol-2-ylmethyl)phosphonic Acid
Sylvie Pailloux,† Cornel Edicome Shirima,† Karen Ann Smith,† Eileen N. Duesler,†
Robert T. Paine,*,† Neil J. Williams,‡ and Robert D. Hancock‡
†Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, New Mexico 87131, and
‡Department of Chemistry and Biochemistry, University of North Carolina-Wilmington, Wilmington,
North Carolina 28403
Received May 28, 2010
An efficient three step synthesis of (benzoxazol-2-ylmethyl)phosphonic acid (6-H2) is described along with IR, mass
spectrometry (MS), and 1H, 13C, and 31P NMR spectroscopic characterization data, and a single crystal X-ray diffraction structure
determination. 6-H2 is unstable in acidic aqueous solutions (pH < 4) undergoing ring-opening to give [(2-
hydroxyphenylcarbamoyl)methyl] phosphonic acid (7-H2) that is characterized by IR, MS, and NMR methods. The protonation
constants (pKa) for 7-H2 have been measured, and crystal structure determinations for (NH4)(7-H) and K(7-H) DMF are
3
described. Reactions of NaOH and KOH with 6-H2 in MeOH/H2O solutions led to isolation and crystal structure determinations of
the salts [Na(6-H) H2O]2, K(6-H), Na3(6)(6-H) H2O, and [K2(6)]2 3H2O. The complexation reactions of 7-H2 with La(III),
3
3
3
Nd(III), and Gd(III), as a function of pH, were also examined by titrametric methods, and a model for the 1:1 anion binding with
Ln(III) cations is proposed.
Introduction
In our group, while defining new coordination environments
for f-element ions using donor functionalized heterocyclic ring
platforms, we have reported efficient routes for the formation of
(phosphinoylalkyl)pyridine and pyridine N-oxide ligands.9-12
These neutral ligands form chelate interactions with lanthanide-
(III)9-11 and plutonium(IV)12 ions, and they function as useful
solvent extraction reagents for Ln(III)/An(III) ions in strongly
acidic aqueous solutions.13 During the course of this work, it was
observed that, in some cases, phosphonate ester derivatives of
alkyl and aryl (phosphinoylalkyl)pyridines and pyridine N-
oxides undergo hydrolysis in strongly acidic aqueous solutions.
Since the resulting phosphonic acids might be expected to
interfere in extraction performance, it has become important to
define the nature of the hydrolysis reactivity of the phosphonate
esters as well as the coordination chemistry displayed by the
resulting phosphonic acids with Ln(III) ions (Chart 1). In this
regard, we have previously reported formation of 3-D or 1-D
chain structures from lanthanides and 1-H2,14 2-H2,14 3-H2,15
and 4-H2.16
Phosphonate diesters, RP(O)(OR)2, are known to undergo
hydrolysis producing the corresponding phosphonic acids,
RP(O)(OH)2.1 Under gentle physiological conditions these
conversions are typically slow although rates may be en-
hanced by acid or base catalysis. This reactivity has attracted
wide attention in the context of elucidating the mechanisms
for phosphate diester hydrolysis and related enzyme cata-
lyzed hydrolysis of RNA and DNA.2-5 In inorganic and
materials chemistry, the coordination properties of phospho-
nic acids have also attracted notice. In combination with
p-, d-, and f-block metal ions, these species produce a wide
array of amorphous, microporous solids as well as intricate,
crystalline one-dimensional (1-D), two-dimensional (2-D),
and three-dimensional (3-D) framework solids.6 By variation
of the steric size and functionality in the R group, chemically
and physically diverse materials are generated that have
unique ion exchange, proton conduction, nonlinear optic
(NLO), sensor or catalyst properties.6-8
(9) Rapko, B. M.; Duesler, E. N.; Smith, P. H.; Paine, R. T.; Ryan, R. R.
Inorg. Chem. 1993, 32, 2164.
*To whom correspondence should be addressed. E-mail: rtpaine@unm.
edu.
(10) Gan, X.; Duesler, E. N.; Paine, R. T. Inorg. Chem. 2001, 40, 4420.
(1) Quin, L. D. In A Guide to Organophosphorus Chemistry; J. Wiley &
Sons: New York, 2000; pp 357-386.
(2) Engel, R. Chem. Rev. 1977, 77, 349 and references therein.
(3) Tsubouchi, A.; Bruice, T. C. J. Am. Chem. Soc. 1995, 117, 7399.
(4) Feng, G.; Tanifum, E. A.; Adams, H.; Hengge, A. C.; Williams, N. H.
J. Am. Chem. Soc. 2009, 131, 12771.
(5) Hilderbrand, R. L. In The role of phosphorus in living systems; CRC
Press: Boca Raton, FL, 1983; pp 97-104.
(6) Clearfield, A. Prog. Inorg. Chem. 1998, 47, 371 and references therein.
(7) Clearfield, A. Dalton Trans. 2008, 6089 and references therein.
(8) Mao, J.-G. Coord. Chem. Rev. 2007, 251, 1493 and references therein.
€
Gan, X.; Paine, R. T.; Duesler, E. N.; Noth, H. J. Chem. Soc., Dalton Trans.
2003, 153.
(11) Gan, X.; Rapko, B. M.; Duesler, E. N.; Binyamin, I.; Paine, R. T.;
Hay, B. M. Polyhedron 2005, 24, 469.
(12) Matonic, J. H.; Neu, M. P.; Paine, R. T.; Scott, B. L. J. Chem. Soc.,
Dalton Trans. 2002, 2388.
(13) Nash, K. L.; Lavallette, C.; Borkowski, M.; Paine, R. T.; Gan, X.
Inorg. Chem. 2002, 41, 5849.
(14) Gan, X.; Binyamin, I.; Rapko, B. M.; Fox, J.; Duesler, E. N.; Paine,
R. T. Inorg. Chem. 2004, 43, 2443.
r
2010 American Chemical Society
Published on Web 09/23/2010
pubs.acs.org/IC

9370 Inorganic Chemistry, Vol. 49, No. 20, 2010
Chart 1. Relevant Chemical Structures
Pailloux et al.
A sample of 10 (3.6 g, 10 mmol) was combined with distilled
water (200 mL) and stirred (5 min). A white solid rapidly formed
which was recovered by filtration, washed with CHCl3 (50 mL),
and dried leaving a white powder, [(HO)2P(O)CH2]C7H4NO
(6-H2): yield, 1.5 g (70%); mp 228-230 °C. IR(KBr, cm-1): 3436
(vs, br), 2925 (s), 2857 (m), 2358 (m), 1731 (m, sh), 1637 (sh,s),
1612 (s, vCN), 1568 (s), 1460 (s), 1398 (m), 1354 (m), 1310 (m),
1239 (vs, vPO), 1200 (s), 1132 (s), 1011 (s), 954 (vs), 852 (w), 809
(w), 746(m), 685(m), 650(m), 544(m), 506(s). NMR(DMSO-d6):
1H (250 MHz) δ 3.43 (d, 2H, JHP = 20.6 Hz, CH2), 7.2-7.4 (m,
2H, Ar), 7.6-7.7 (m, 2H, Ar), 10.29 (2H, OH); 13C{1H} (62.9
MHz) δ 29.8 (d, JCP = 129.9 Hz, CH2), 110.3, 119.1, 124.1,
124.5, 140.9, 150.3, 160.8 (O-CdN); 31P{1H} (101.2 MHz) δ
15.4. ESI-MS: Found (Calcd.) m/z = 212.0109 (212.0113) [M -
H]-, 447.0121 [(M - H)2 þ Na]-. Anal. Calcd. for C8H8NO4P:
C, 45.08; H, 3.78; N, 6.38. Found: C, 43.64; H, 3.96; N, 6.38.
Synthesis of [(2-Hydroxyphenylcarbamoyl)methyl]phosphonic
Acid (7-H2). A sample of 10 (4.2 g, 12 mmol) was combined with
distilled water (200 mL) and stirred. A white solid (6-H2) formed
immediately; however, with continued stirring at 23 °C (3d), the
solid redissolved completely. The resulting solution was extracted
with CHCl3 (3 ꢀ 50 mL), and the aqueous phase filtered and
concentrated byvacuum evaporation. A white solid, [(HO)2P(O)-
CH2C(O)N(H)]C6H4(OH) 7-H2, was recovered: yield, 2.1 g (77%),
mp 180-182 °C. The solid was recrystallized from MeOH.
IR(KBr, cm-1): 3432 (s, br, vOH), 2250 (m), 2124 (m), 1675
(m, vCO), 1609 (w), 1535 (m), 1454 (m), 1380 (w), 1329 (w), 1246
(m, υPO), 1051 (vs), 1024 (vs), 824 (m), 762 (m), 623 (w). NMR
(DMSO-d6): 1H (250 MHz) δ 2.9 (d, JHP = 21 Hz, 2H, H3), 6.7
(m, 1H, H11), 6.8 (m, 1H, H9), 6.9 (m, 1H, H10), 7.4 (s, 3H, H1,
H2, H7) 7.9 (dd, JHH = 8 Hz, JHH = 1 Hz, 1H, H12), 9.2 (s, 1H,
H5); 13C{1H} (62.9 MHz) δ 38.5 (d, JCP = 125.5 Hz, C3), 114.9
(C9), 118.6 (C11), 120.5 (C12), 123.8 (C10), 126.3 (C8), 146.6 (C6),
164.1 (C4); 31P{1H} (101.2 MHz) δ 18.1. ESI-MS: Found
(Calcd.) m/z = 230.0190 (230.0218) [M - H]-. Anal. Calcd
for C8H10NO5P: C, 41.57; H, 4.36; N, 6.06. Found: C, 40.96; H,
4.24; N, 5.88.
Recently, we have also utilized additional heterocyclic plat-
forms to develop new ligand environments, and this includes
the formation of (phosphinoylmethyl)benzoxazoles, 5.17 In
the course of that study, we examined the hydrolytic stability
of phosphonate diester derivatives of 5 (R = OEt) and noted
the formation of the phosphonic acid 6-H2. We report here an
optimized synthesis of the phosphonic acid 6-H2, its neutral-
ization chemistry, the acid-promoted ring-opening of the
oxazole ring that produces 7-H2, the isolation and structural
characterization of several NH4þ, Naþ, and Kþ salts of 6-H2
and 7-H2, and initial characterization of the solution com-
plexation chemistry of 7-H2 with Ln(III) cations.
Ligand pKa and Complexation Constant Determinations. The
protonation constants of 7-H2 (pKn) and formation constants
(log K) for 7-H2 with La(III), Nd(III), and Gd(III) were
determined by UV-visible spectroscopy following procedures
similar to those described by Choppin et al.19 UV-visible
spectra were recorded by using a Varian 300 Cary 1E UV-
visible Spectrophotometer controlled by Cary Win UV Scan
Application version 02.00(5) software. A VWR sympHony
SR60IC pH meter with a VWR sympHony gel epoxy semimicro
combination pH electrode was used for all pH readings. These
were made in a thermostatted external titration cell, with N2
bubbled through the cell to exclude CO2. The pH meter was
calibrated prior to every titration by means of an acid-base
titration where measured potentials were fitted to calculated pH
values to yield a Nernstian slope and Eo for the cell. The cell
containing 50 mL of ligand/metal solution was placed in a
temperature regulated water bath (25.0 ( 0.1 °C), and a
peristaltic pump was used to circulate the solution through a
1 cm quartz flow cell situated in the spectrophotometer. The pH
was altered in the range 2 to 7 by additions to the external
titration cell of small amounts of HClO4 or NaOH as required
using a micropipet. After each adjustment of pH, the system was
allowed to mix by operation of the peristaltic pump for 15 min
prior to recording the spectrum.
Experimental Section
General Information. The 2-methylbenzoxazole (8) and other
organic reagents employed in the ligand syntheses were pur-
chased from Aldrich Chemical Co. and used without purifica-
tion. Organic solvents were purchased from VWR. Infrared
spectra were recorded on a Bruker Tensor 27 benchtop spectrom-
eter, and solution NMR spectra were measured on Bruker
FX-250 and Avance 500 spectrometers. The NMR standards
were TMS (1H, 13C) and 85% H3PO4 (31P), and downfield shifts
were assigned as þδ (ppm). Elemental analyses were obtained
from Galbraith Laboratory and mass spectra were recorded in
the UNM Mass Spectroscopy Facility.
Synthesis of (Benzoxazol-2-ylmethyl)phosphonic Acid (6-H2).
A sample of 2-[(diethoxyphosphinoyl)methyl]benzoxazole18 (9)
(1.9 g, 7.1 mmol) was combined with Me3SiBr (2.4 g, 15.6 mmol),
stirred (23 °C, 4 h), and the reaction progress followed by TLC
(EtOAc). Excess Me3SiBr was vacuum evaporated leaving a pale
pink oil, [(Me3SiO)2P(O)CH2]C7H4NO (10): yield, 2.4 g (92%).
NMR (CDCl3): 1H (250 MHz) δ 0.28 (s, 18H, Si(CH3)3), 3.60 (d,
2H, JHP = 22.3 Hz, CH2), 7.3 (m, 2H, Ar), 7.5 (m, 1H, Ar), 7.7 (m,
1H, Ar); 13C{1H} (62.9 MHz) δ 0.5 (Si(CH3)3), 29.7 (d, JCP
=
143.1 Hz, CH2), 109.7, 118.6, 123.9, 124.5, 139.5, 150.1, 159.0 (d,
J
CP = 11.3 Hz, O-CdN); 31P{1H} (101.2 MHz) δ -1.4.
7-H2 has fairly intense bands in its UV spectrum because of
π-π* transitions from the phenolic aromatic ring, and these
were used to monitor complex-formation in solution. The
variation of the spectra of 7-H2 in 0.1 M NaClO4 solutions as
a function of pH at 25 °C are displayed in Figure 1. Three
protonation constants were determined for 7-H2 (Table 1) by the
(15) Gan, X.; Rapko, B. M.; Fox, J.; Binyamin, I.; Pailloux, S.; Duesler,
E. N.; Paine, R. T. Inorg. Chem. 2006, 45, 3741.
(16) Gan, X.; Binyamin, I.; Rapko, B. M.; Fox, J.; Duesler, E. N.; Paine,
R. T. Polyhedron 2006, 25, 3387.
(17) Shirima, C. E. Ph.D. Thesis, University of New Mexico, Albuquerque,
NM, May, 2009 and references therein.
(18) Minami, T.; Isonaka, T.; Okada, Y.; Ichikawa, J. J. Org. Chem. 1993,
58, 7009.
(19) Xia, Y. X.; Chen, J. F.; Choppin, G. R. Talanta 1996, 43, 2073.

Article
Inorganic Chemistry, Vol. 49, No. 20, 2010 9371
used to confirm the metal:ligand complex stoichiometry. An attempt
was made to measure log K(MLH) for 7-H2 with Lu(III) as the
smallest of the Ln(III) ions, but precipitation of Lu(III) hydroxide
prevented determination of a reliable value of log K(MLH)
.
Phosphonic Acid Neutralization Reactions. NaOH þ (6-H2).
A sample of 6-H2 (0.13 g, 0.62 mmol) was dissolved in MeOH
(10 mL), and aqueous NaOH solution (0.1 M) was slowly added
until the solution reached pH 7. The solution was then allowed
to evaporate leaving a white powder, Na{[(HO)(O)2PCH2]C7H4-
NO} H2O, Na(6-H) H2O, that was rinsed with acetone and
3
3
allowed to dry: yield, 0.148 g (87%); mp >250 °C. NMR
(DMSO-d6): 31P{1H} δ 12.2. Anal. Calcd. for C8H9NO5PNa: C,
37.96; H, 3.58; N, 5.53. Found: C, 37.40; H, 2.76; N, 5.86.
NaOH þ (6-H2). In a second procedure, 6-H2 (0.208 g,
0.976 mmol) in MeOH (20 mL) was treated with NaOH solution
(0.1 M, 1.95 mmol) until the solution showed pH 12.7. The mixture
was stirred (12 h), and the solution evaporated to dryness.
The white solid residue was washed with MeOH (10 mL) and
acetone (10 mL) and allowed to dry in air leaving a white
Figure 1. Absorption spectra of2.00ꢀ 10-5 M 7-H2 in0.1 M NaClO4 as
a function of pH. The variation of absorbance as a function of pH can be
fitted20 to yield the three protonation constants reported in Table 1.
powder, Na3(6)(6-H) H2O. NMR (DMSO-d6): 31P{1H} δ 13.1.
3
KOH þ (6-H2). A sample of 6-H2 (0.11 g, 0.52 mmol) was
dissolved in MeOH (20 mL) and slowly combined with aqueous
KOH solution (0.1 M, 2.0 mmol). The mixture was stirred (12 h,
23 °C) and allowed to evaporate leaving a solid residue. This was
dissolved in MeOH/CH3CN, filtered and evaporated. The
residue was extracted with dimethylformamide (DMF), the
insoluble fraction recovered and recrystallized from hot MeOH
leaving crystalline [K2(6)]2 3H2O. The DMF filtrate was
3
evaporated, and the residue recrystallized from MeOH/DMF
giving K(6-H).
KOH þ (6-H2). In a 2:1 stoichiometric combination, a sample
of 6-H2 (0.21 g, 0.98 mmol) in MeOH (25 mL) was combined
with KOH (0.1 g, 1.95 mmol) in MeOH (15 mL), and the clear
solution stirred under dry nitrogen (12 h). The final solution
(pH 8) was allowed to slowly evaporate leaving a brown solid:
yield, 0.22 g (44%, based on [K2(6)]. NMR (DMSO-d6): 31P{1H}
δ 11.9. Anal. Calcd for C16H18N2O11P2K4: C, 30.38; H, 2.87; N,
4.43. Found: C, 30.69; H, 2.96; N, 4.43.
Figure 2. Absorption spectra of 2.00 ꢀ 10-5 M 7-H2 plus 2 ꢀ 10-5
M
Gd(III) in 0.1 M NaClO4 as a function of pH. The initial spectrum was
recorded at pH 1.85(lower spectrum), and the final pH was 10.97 (upper
spectrum).
NH4OH þ (7-H2) (2:1). A sample of 7-H2 (0.25 g, 1.1 mmol)
was dissolved in water (15 mL) resulting in a pH 1.5 solution.
Aqueous 0.1 M NH4OH solution was added dropwise until the
mixture showed pH 9.2. The solution was then evaporated
slowly leaving colorless needles, NH4 (7-H). NMR (DMSO-d6):
31P{1H} δ 13.6.
KOH þ (6-H2). In a 1:1 stoichiometric combination a sample
of 6-H2 (0.13 g, 0.62 mmol) in MeOH (20 mL) was combined
with KOH (0.035 g, 0.62 mmol) in water (100 mL), and the clear
solution stirred (12 h) resulting in a pH 4 solution. This was
allowed to evaporate leaving a white solid residue, K(7-H): yield
0.156 g (93%); mp 140-141 °C. The solid was washed with
DMF and recrystallized from MeOH by slow evaporation. The
Table 1. Protonation Constants, and log K(MLH) Values for 7-H2 (LH3) with
Lanthanide Ions, in 0.1 M NaClO4 (25.0 ( 0.1 °C)
cation
Hþ
equilibria
log K
L3- þ Hþ / LH2-
10.22(6)
7.39(3)
2.2(4)
10.14(5)
6.5(1)
LH2- þ Hþ / LH2
-
LH2 þ Hþ / LH3
-
La(III)
Nd(III)
Gd(III)
LaL þ Hþ / [LaLH]þ1
La3þ þ LH2- / [LaLH]þ1
NdL þ Hþ / [NdLH]þ1
Nd3þ þ LH2- / [NdLH]þ1
GdL þ Hþ / [GdLH]þ1
Gd3þ þ LH2- / [GdLH]þ1
9.71(5)
6.5(1)
10.08(5)
6.2(1)
crystals were shown by X-ray crystallography to be K(7-H)
3
DMF. IR (KBr, cm-1): 3440 (s, br, vOH), 2248 (m), 2121 (m),
1665 (m), 1536 (w), 1454 (w), 1382 (w), 1242 (w), 1044 (vs, vPO),
823 (m), 762 (m), 573 (m). NMR (DMSO-d6): 1H (250 MHz) δ
2.56 (d, JPH = 18.7 Hz, 2H, CH2), 4.46 (br, 4H), 6.60 (m),
6.79 (m), 7.81 (m), 7.88 (m), 10.07. 31P{1H} (101.3 MHz) δ 12.5.
Anal. Calcd for C11H16KN2O6P: C, 38.59; H, 4.71; N, 8.18.
Found: C, 37.78; H, 4.83; N, 7.69.
variation in absorbance as a function of pH at five different
wavelengths. Fitting of theoretical absorbance versus pH curves
was accomplished using the SOLVER module of EXCEL.20 The
standard deviations given in Table 1 were obtained using the
SOLVSTAT macro.20
Formation constants with La(III), Nd(III), and Gd(III) as
representative lanthanide (Ln) ions were measured by repeating
the titrations with 7-H2 in the presence of 1 equiv of the Ln(III)
ion. The spectra of the 1:1 7-H2/Gd(III) system as a function of
pH are shown in Figure 2. From the displacement of the
protonation equilibria to lower pH values, the formation con-
stants were calculated21 and the resulting values are displayed in
Table 1. A continuous variation analysis (Job’s method) was
X-ray Diffraction Analyses. Crystals were placed in glass
capillaries and mounted on a Bruker X8 Apex2 CCD-based
X-ray diffractometer with a normal focus Mo-target X-ray tube
˚
(λ = 0.71073 A), operated at 1500 W (50 kV, 30 mA), and an
Oxford Cryostream 700 low temperature device. Full spheres of
data were collected, and the frames integrated with the Bruker
SAINT software package.22 The data was processed with
(20) Billo, E. J. EXCEL for Chemists; Wiley-VCH: New York, 2001.
(21) Martell, A. E.; Motekaitis, R. J. The Determination and Use of
Stability Constants; VCH Publishers: New York, 1989.
(22) Sheldrick, G. M. SAINTPlus, v.7.01; Bruker Analytical X-ray: Madison,
WI, 2003.

9372 Inorganic Chemistry, Vol. 49, No. 20, 2010
Pailloux et al.
Table 2. Crystallographic Data
6-H2
[Na(6-H) (H2O)]2
3
Na3(6)(6-H) H2O
3
K(6-H)
[K2(6)]2 3H2O
3
NH4(7-H)
K(7-H) DMF
3
empirical formula
formula weight
crystal system
C8H8NO4P
213.12
orthorhombic triclinic
C16H18N2Na2O10P2 C8H7.5NNa1.5O4.5P C8H7KNO4P
C16H18K4N2O11P2 C8H13N2O5P C11H16KN2O6P
632.66
506.24
255.10
monoclinic
P2(1)/c
251.22
monoclinic
P2(1)/c
248.17
monoclinic
P2(1)/c
342.33
orthorhombic
Pbca
orthorhombic
Aba2
space group
unit cell dimensions
Pca2(1)
P1
˚
a, A
19.883(2)
5.6194(6)
7.814(1)
90
4.8192(3)
14.0855(7)
15.6805(9)
80.514(3)
81.492(3)
85.122(3)
1036.3(1)
2
16.9793(9)
5.4083(3)
21.628(1)
90
15.2517(7)
4.6921(2)
14.1701(7)
90
34.134(2)
9.7662(6)
7.1209(4)
90
19.8602(9)
7.1524(3)
8.1497(3)
90
7.4875(5)
14.2950(8)
28.810(2)
90
˚
b, A
˚
c, A
R, deg
β, deg
γ, deg
volume
Z
T, K
90
90
98.723(3)
90
98.359(2)
90
90
90
97.563(2)
90
90
90
873.1(2)
4
228(2)
1963.1(2)
8
183(2)
1003.28(8)
4
228(2)
2373.8(2)
4
1147.58(8)
4
3083.6(3)
8
228(2)
1.622
0.311
228(2)
1.770
0.946
228(2)
1.436
0.248
228(2)
1.475
0.475
density, g cm-3
absorption coeff, mm-1 0.301
1.621
1.726
0.345
1.663
0.680
min/max transmission
reflection collected
independent
0.850/0.970
21435
2969[0.0239]
0.8881/0.9789
33065
7917[0.0363]
0.890/0.972
42064
6805[0.0298]
0.834/0.944
34844
4403[0.0204]
0.6751/0.9446
36250
4527[0.0226]
0.8711/0.9875 0.8276/0.9474
26858
3477[0.0284]
62611
4724[0.0280]
reflections [Rint
final R indices
[I > 2σ(I)]
]
R1 (wR2)
final R indices
(all data) R1(wR2)
0.0243(0.0674) 0.0373(0.0950)
0.0248(0.0679) 0.0554(0.1037)
0.0496(0.1454)
0.0564(0.1489)
0.0265(0.0727) 0.020190.0467)
0.0324(0.0797) 0.0208(0.0470)
0.0340/0.0937 0.0516/0.1332
0.0418/0.0997 0.0644/0.1424
SADABS,23 and the structures solved and refined with the
Bruker SHELXTL software package.24 Data collection and
lattice parameters are summarized in Table 2. Specific com-
ments related to each structure follow. 6-H2: Colorless prism
(0.55 ꢀ 0.46 ꢀ 0.09 mm) recrystallized from MeOH/MeCN. The
structure was solved and refined in the chiral orthorhombic
space group Pca2(1). The presence of the P atom permitted
determination of the absolute configuration (Flack x =
0.06(6)). All non-hydrogen atoms were refined anisotropically,
and ring H atoms were placed in ideal positions with fixed
increase of R1 by 5%. The H-atom on O4 was allowed to vary
in position and Uiso. [K2(6)2]2 3H2O: Colorless plates (0.45 ꢀ
3
0.26 ꢀ 0.06 mm) recrystallized from hot MeOH. All non-hydrogen
atoms were refined anisotropically, and H-atoms on ring C-atoms
placed in idealized positions with fixed Uiso = 1.2Uequiv of the
parent atom. The H-atoms on C8 were placed in idealized positions
with Uiso = 1.5Uequiv of C8. The H-atoms on the water molecules
were allowed to vary in position and Uiso. NH4(7-H): Colorless
plate (0.57 ꢀ 0.37 ꢀ 0.05 mm) recrystallized from H2O/MeOH. All
non-hydrogen atoms were refined anisotropically, and the H-atoms
Uiso = 1.2 Uequiv of the parent atom. H3 on O3 was placed in an
ideal position with fixed Uiso = 1.5Uequiv of O3. H2 on O2 and H1a
and H1b on C1 were allowed to vary in position andUiso. [Na(6-H)
H2O]2: Colorless needles (0.39 ꢀ 0.09 ꢀ 0.07 mm) recrystal-
lized from MeOH. All non-hydrogen atoms were refined aniso-
tropically and H-atoms on C-atoms were placed in idealized
positions with fixed Uiso = 1.2 Uequiv of the parent atom. H-atoms
on O-atoms were allowed to vary in position and Uiso. The initial
assignment of the ring N and O atoms was tested by reversing the
on all of the C-atoms were placed in idealized positions with Uiso =
1.2Uequiv of the parent atom. The H-atoms on the N1, O2, and O5
atoms were allowed to vary in position and Uiso. K(7-H) DMF:
Colorless plate (0.41 ꢀ 0.39 ꢀ 0.16 mm) recrystallized from
MeOH/DMF. The solvent DMF molecule was disordered over
two sites with relative occupancies 72/28%. All non-hydrogen
atoms except the minor site atoms C9A, C10A, and C11A were
refined anisotropically. The H-atoms on the ring C-atoms were
included in idealized positions with Uiso = 1.2Uequiv of the parent
atom. The H-atoms on C8 were placed in idealized positions with
3
3
atom types. This led to increased Rfactors by 2-3%. Na3(6)(6-H)
3
H2O: Colorless plate (0.34 ꢀ 0.28 ꢀ 0.07 mm) recrystallized
from MeOH. All non-hydrogen atoms were refined anisotropi-
cally, and H-atoms on C-atoms placed in idealized positions with
Uiso = 1.2Uequiv of the parent atom. The H-atom on O8 was
located in a difference map, and it was allowed to vary in position
and Uiso. The positions of H-atoms on O9 were deduced based on
the likely H-bonding scheme: O9 has close approaches to N1[x, y, z]
and O6[x, y-1, zþ1]. The positions were fixed with O9-H 0.85
Uiso = 1.5Uequiv of C8. The H-atoms on the O1, O3, and N1 atoms
were allowed to vary in position and Uiso
.
Results and Discussion
The synthesis of the target (benzoxazol-2-ylmethyl)phos-
phonic acid (6-H2) employed a three-step sequence starting
with commercially available 2-methyl benzoxazole (8) as
summarized in Scheme 1. The conversion of 8 to 2-[(diethoxy-
phosphinyl)methyl] benzoxazole (9) has been previously
described by Minami et al.18 and others.25 The Minami pro-
cedure was adopted in toto except it was performed with a
˚
Aand Uiso =1.5Uequiv of O9. K(6-H):Colorless prism (0.28 ꢀ 0.16 ꢀ
0.09 mm) recrystallized from MeOH/DMF. All non-hydrogen
atoms were refined anisotropically, and H-atoms on C-atoms
were placed in idealized positions with fixed Uiso = 1.2 Uequiv of the
parent atom. There is a small disorder in the N1/O1 positions:
primary positions 86.5%; secondary positions 13.5%. The atom
assignments of N1 and O1 were interchanged resulting in an
(25) An alternative Arbusov synthesis of 9 has been reported involving the
combination of 2-(bromomethyl)-1,3-benzoxazole and P(OEt)3 at 150 °C. In
our hands this synthesis was not as predictable as the approach described
by Minami.18Kosaka, T.; Wakabayashi, T. Heterocycles 1995, 41, 1995.
Anthony, N. D.; et al. J. Med. Chem. 2007, 50, 6116; Another alternative route
may exist based upon a reaction involving alcohol elimination and subsequent
condensation between R(R0O)P(O)CH2CH(OR00)2 and 2-aminophenol: Razumov,
A. I.; Gurevich, P. A.; Liorber, B. G. Zhur. Obsh. Khim. 1969, 39, 392.
(23) Sheldrick, G. M. SADABS, Program for Empirical Absorption
€
€
Correction of Area Detector Data, v.2.10; University of Gottingen: Gottingen,
Germany, 2003.
(24) Sheldrick, G. M. SHELXTL, v.6.12; Bruker Analytical X-ray: Madison,
WI, 2001.

Article
Inorganic Chemistry, Vol. 49, No. 20, 2010 9373
Scheme 1
10-fold scale-up. At that scale, 9 is obtained in 73% yield
(81% lit.) as a colorless oil. Mass spectroscopic and 1H NMR
data are similar to data provided in the literature,18 and addi-
tional IR and NMR spectra, recorded in the present study,
are consistent with the proposed structure of 9.26
to the N = C-O unit of the oxazole fragment that closely com-
pares with δ 158.2 (JCP = 10 Hz) for the related carbon atom
in 9. The 1H and 13C{1H} NMR resonances for the methylene
group separating the P atom and benzoxazole ring in 10 appear
at δ 3.60 (JPH = 22.3 Hz) and δ 29.7 (JCP = 143.1 Hz), respec-
tively, and these data are similar to NMR data for 9: 1H δ 3.57
(JPH = 21.7 Hz), 13C{1H} δ 27.6 (JCP = 139.2 Hz). As ex-
pected for a silyl phosphonate ester,14-16,28 the 31P resonance
for 10, δ -1.4, is significantly upfield of the resonance in the
ethyl ester 9, δ 20.0.26 The 31P resonance for 10 is also upfield of
the shifts recorded for (Me3SiO)2P(O)CH2C(O)NEt2, δ 2.828
and [(Me3SiO)2P(O)CH2]2, δ 11.6.33
The subsequent aqueous hydrolysis of 10 is rapid and
quantitative providing 6-H2 as a white solid. This compound
was quickly recrystallized from cold water and recovered in
70% yield. The compound displays a parent ion species [M -
H]-1, as well as a dimer-sodium ion complex [(M - H)2 þ
Na]-1 in its negative ion mode ESI-MS. The infrared spectrum
contains strong bands at 1612 and 1239 cm-1 that are tenta-
tively ascribed to vCN and vPO, respectively, based upon IR data
for 9.17,18,26 There is also a broad, strong band centered at 3436
cm-1 that is assigned to PO-H stretching modes that are not
present in the spectra for the diesters 9 and 10. As expected, the
silyl group NMR resonances that were present in the 1H and
13C NMR spectra of 9 are now absent in 6-H2; however,
resonances for the methylene group, 1H δ 3.4 (JPH = 20.6 Hz),
13C{1H} δ 29.8 (JCP = 129.9 Hz) and the N = C-O unit,
13C{1H} δ 160.8, confirm the retention of the benzoxazole ring
structure. In addition, a 1H NMR resonance at δ 10.29 appears
for the phosphonic acid protons. The 31P{1H} resonance for
6-H2 in DMSO-d6 appears at δ 15.4. This is slightly upfield
from the value of δ 23.6 (CDCl3) observed for 2-[(HO)2P-
(O)CH2]C5H4NO (11)14 and downfield from the value of δ17.9
(CD3CN/H2O) in (HO)2P(O)CH2C(O)NEt2.28 It is noted that
the 31P NMR shifts for all of these compounds are very solvent
and pH sensitive.
Although some phosphonate esters undergo partial hydro-
lysis under relatively mild conditions,14,16 more forcing con-
ditions, for example, 6 M HCl with reflux,27 are typically
required for complete conversion. Such conditions are dele-
terious to the benzoxazole ring, vide infra; therefore, another
synthetic approach was required to obtain 6-H2. We15,28 and
others29-32 have reported that treatment of organyl phos-
phonate esters with Me3SiCl or Me3SiBr under mild condi-
tions usually leads to formation of the corresponding silyl
ester, and subsequent aqueous hydrolysis provides the de-
siredphosphonic acid. In the present case, treatment of9 with
a slight excess of Me3SiBr at 23 °C results in formation of a
faintly pink oil, (benzoxazol-2-ylmethyl) phosphonic acid
bis-(trimethylsilyl) ester, (10) in 92% yield. It is noted that the
silylation reaction does not occur at a useful rate with Me3SiCl.
Compound 10 displays a strong IR band at 1240 cm-1, that is
tentatively assigned to the vPO stretching mode.17 Several broad,
overlapping adsortions appear in the region 1650-1500 cm-1
,
but confident assignment of one of these to vCN of an intact
benzoxazole ring is not possible. The 1H and 13C{1H} NMR
spectra, however, provide ample evidence for the survival of the
oxazole ring. For example, the 13C{1H} NMR spectrum con-
tains a doublet resonance at δ 159.0 (JCP = 11.3 Hz) assigned
(26) Additional characterization data for 9. IR(KBr, cm-1): 2984(m),
2921(m), 1689(w), 1613(m, vCN), 1570(m), 1485(m), 1397(w), 1256(s, vPO),
1164(m), 1107(m), 1028(s), 967(s), 752(m), 653(w), 545(2), 507(w). 1H NMR
(250 MHz, CDCl3): δ 1.31(t, JHH = 7.2 Hz, 6H, OCH2CH3), 3.57(d, JHP
=
21.7 Hz, 2H, PCH2), 4.15(q, JHH = 6.4 Hz, 4H, OCH2), 7.28(m, 2H, Ar),
7.66(m, 1H, Ar), 7.68(m, 1H, Ar). 13C{1H} NMR (62.9 MHz, CDCl3): δ
15.8(d, JCP = 5.8 Hz, C1), 27.6(d, JCP = 139.2 Hz, C3), 62.5(d, JCP = 6.4 Hz, C2),
110.0(s), 119.4(s), 123.9(s), 124.5(s), 140.8(d, JCP = 1.3 Hz), 150.6(s),
158.2(d, JCP = 10 Hz, C4). 31P{1H} NMR (101.2 Hz, CDCl3): δ 20.0
(27) Engel, R. E. Synthesis of Carbon-Phosphorus Bonds; CRC Press: Boca
Raton, FL, 1988; p 21.
(28) Conary, G. C.; McCabe, D. J.; Caudle, L. J.; Duesler, E. N.; Paine,
R. T. Inorg. Chim. Acta 1993, 207, 213.
(29) Morita, T.; Okamoto, Y.; Sakurai, H. Bull. Chem. Soc. Jpn. 1978, 51,
2169.
(30) McKenna, C. E.; Higa, M. T.; Cheng, N. H.; McKenna, M.
Tetrahedron Lett. 1977, 155.
(31) Rabinowitz, R. J. Org. Chem. 1963, 38, 2975.
(32) Neff, G. A.; Page, C. J.; Meintjes, E.; Tsuda, T.; Pilgrim, W.-C.;
Roberts, N.; Warren, W. W., Jr. Langmuir 1996, 12, 238.
The spectroscopically deduced molecular structure of 6-H2
was confirmed by a single crystal X-ray diffraction structure
determination. A view of the molecule is shown in Figure 3,
and selected bond lengths are provided in Table 3. As ex-
pected, the structure contains a 2-methyl benzoxazole frag-
ment bonded to a -P(O)(OH)2 unit. The P1-C1 bond length,
ꢀ
(33) Pudovik, M. A.; Terenteva, S. A.; Kibardina, L. K.; Pudovik, A. N.
Russ. J. Gen. Chem. 2006, 76, 714.

9374 Inorganic Chemistry, Vol. 49, No. 20, 2010
Pailloux et al.
resonance at δ 14 that disappears as the solid is consumed by
hydrolysis. While the bulk of the solid is present, a resonance
at δ 17 appears and increases in intensity as 7-H2 is produced.
The rate of this conversion reaction is increased with increas-
ing temperature and decreasing aqueous solution pH caused
by addition of a small amount of HCl.
Compound 7-H2 displays a parent ion [M - H]- in its
negative ion mass spectrum that confirms the addition of H and
OH to 6-H2. The infrared spectrum for 7-H2 has several of the
same fingerprint features as 6-H2; however, the disappearance
of a very strong bond at 1612 cm-1, tentatively assigned to vCN
in 6-H2, and appearance of a strong, sharp band at 1675 cm-1
,
Figure 3. Molecular structure of [(HO)2P(O)CH2]C7H4NO, (6-H2)
(20% thermal ellipsoids).
tentatively assigned to vCO in 7-H2, are consistent with the
formation of the open ring structure.17 The 13P{1H} NMR
spectrum of 7-H2 in DMSO-d6 consists of a single resonance,
δ18.1, that is downfield of the resonance for 6-H2 in DMSO-d6,
δ 15.4, and both chemical shifts are solvent and pH dependent.
The 31P NMR resonance for 7-H2 is upfield of the resonance for
the structurally related phosphonate diester, (EtO)2P(O)CH-
(CH3)C(O)N(H)Ph, δ 23.8.41 The 1-D 1H and 13C{1H}, 2-D
˚
1.818(1) A, is similar to the P-C bond length in the related
2-[(diphenylphosphinoyl)methyl] benzoxazole, 2-[(Ph)2P-
(O)CH2]C7H4NO (12), 1.823(1) A.17 The PdO bond length
˚
˚
in 6-H2, P1-O1, 1.4894(9) A, is significantly shorter than the
˚
P-OH bond lengths, P1-O2, 1.5371(8) A, and P1-O3,
˚
1.5387(9) A; however, it is similar to the PdO bond length
˚
in 12, 1.4831(8) A. The twist of the phosphonate PdO bond
COSY, DEPT, 1H - 13C HMQC, 1H - 13C HMBC, 1H - 15
N
vector relative to the methyl benzoxazole fragment is indi-
cated by the angle between the planes P1O1C1 and
C1C2N1C8C7C6C5C4C3O4, 96.9°, and this can be com-
pared with the related angle in 12, 56.8°. The difference may,
in part, result from the hydrogen bonding that takes place
in 6-H2 where the phosphonic acid H-atoms interact with
a ring N atom and a phosphoryl O-atom in neighboring
molecules.34
HMQC, and 1H - 15N HMBC NMR experiments42 provide for
complete assignments for the ring-opened structure, and rep-
resentative spectra are included in the Supporting Informa-
tion. It is noted that the 1H and 13C NMR resonances for the
methylene group (C3), 1H δ 2.9; 13C 38.5, are shifted from the
values displayed by 6-H2.
Attempts to grow X-ray diffraction quality crystals of 7-H2
failed. However, crystals of ammonium [(2-hydroxyphenylcar-
bamoyl)methyl]hydrogen phosphonate, [NHþ4 ][(HO)P(O)2-
CH2C(O)N(H)(C6H4OH)-], NH4(7-H), were obtained from
the 1:1 reaction of NH4OH and 7-H2 in water, and the
molecular structure was determined by X-ray diffraction meth-
ods. A view of the molecule is shown in Figure 4, and selected
bond distances are listed in Table 3. The structure determina-
tion confirms the ring-opened structure with bonding param-
eters similar to those reported for [NH2C(CH3)2CH2-
C(O)CH2C(CH3)2þ][(HO)(O)2PCH2C(O)NEt-4 ] (13).28 The
phosphorus atom adopts a pseudotetrahedral geometry with
While attempting to determine the pKa’s and examining
stoichiometric neutralization reactions of 6-H2 it was noted
that the compound, under some conditions, is subject to ring-
opening chemistry that results in the formation of a white
solid, [(2-hydroxyphenylcarbamoyl)methyl]phosphonic acid,
7-H2, in variable amounts. This was not entirely unexpected
based upon literature reports of ring-opening for other
benzoxazole compounds.35-39 Therefore, an effort was made
to devise an optimized synthesis for 7-H2. As depicted in
Scheme 2, extending the reaction time for aqueous hydrolysis
of 10 provides a suitable condition for obtaining 7-H2 in high
yield with analytical purity.40 Conversion of 10 to 6-H2, as
noted above, is very rapid as evidenced by immediate forma-
tion of a precipitate when water is added to neat samples of
10. However, continued rapid stirring of the mixture over
several days results in dissolution of the precipitate and
formation of a clear solution from which 7-H2 is isolated in
good yield.
˚
two shorter P-O bond lengths, P1-O1 1.4944(9) A and P1-
˚
˚
O3 1.5046(9) A, and a longer P1-O2 bond length, 1.581(1) A.
The last belongs to the protonated P-OH group. Similar P-O
and P-OH bond lengths appear in 13. The P1-C1, C1-C2,
C2-O4, and C2-N1 bond lengths in NH4(7-H) 1.814(1),
˚
1.508(2), 1.243(1), and 1.338(2) A also are similar to the related
parameters in 13: (1.799(4) A, 1.500(7) A, 1.224(6) A, and
˚
˚
˚
The conversion of 6-H2 to 7-H2 was followed by 31P NMR.
In water, 6-H2 is only slightly soluble, but it displays a single
˚
1.340(6) A. As expected, however, C2-N1 in NH4(7-H) is
˚
significantly longer than C2-N1 in 6-H2 1.294(1) A, and
C2-O4 is much shorter than in 6-H2, 1.355(1) A.43 There are
˚
several hydrogen bonding interactions in the molecule that
involve either the hydrogen phosphonate proton or the
(34) Hydrogen bonding interactions in 6-H2 include O2-H2 N1A: O2-
H2 0.77(2) A, N1A H2 1.81(2) A, O2 N1A 2.560(1) A, O2-H N1A
3 3 3
˚
˚
˚
3 3 3
3 3 3
3 3 3
˚
˚
ammonium protons with the shortest being, O2-H2 O3A
163(3)°; O3-H3 O1B: O3-H3 0.83 A, O1B H3 1.67 A, O3 O1B
3 3 3
3 3 3 3 3 3 3 3 3
˚
2.473(1) A, O3-H3 O1B 162.1°.
3 3 3
(35) Bruylants, A.; deMedicis, E. F. Cleavage of the Carbon-nitrogen
double bond. In The Chemistry of the Carbon-Nitrogen Double Bond; Patai,
S., Ed.; J. Wiley: New York, 1970.
(41) Tay, M. K.; Abont-Jaudet, E.; Collignon, N.; Savignac, P. Tetra-
hedron 1989, 45, 4415.
(42) The long-range 1H-15N heteronuclear shift correlation NMR experi-
ments using natural abundance 15N were aided by literature reports:
(a) Besse, P.; Combourieu, B.; Boyse, G.; Sancelme, M.; DeWever, H.; Deloit,
A.-M. Appl. Environ. Microbiol. 2001, 67, 1412. (b) Barnwal, R. P.; Rout, A. K.;
Chang, K. V. R.; Atreya, H. S. J. Biomol. NMR 2007, 39, 259.
(36) Werstiuk, N. H.; Ju, C. Can. J. Chem. 1989, 67, 812.
(37) Ono, M.; Yamakawa, K.; Kobayashi, H.; Itoh, I. Heterocycles 1988,
27, 881.
(38) Cole, E. R.; Crank, G.; Sumantu Aust. J. Chem. 1986, 39, 295.
(39) Hirota, T.; Koyama, T.; Basho, C.; Nauba, T.; Sasaki, K.; Yamato,
M. Chem. Pharm. Bull. 1977, 25, 3056.
(40) Bookser, B. C.; Dong, Q.; Reddy, K. R. World Pat. Appl. WO 01/
66553 A2. This document suggests that 7-H2 may be obtained by combina-
tion of 2-hydroxyaniline and diethylphosphonoacetic acid with EDC/HOBT
in DMF.
(43) Examination of 79 structures listed in the Cambridge Crystallo-
graphic Data files that contain the benzoxazline fragment, reveals that 18
˚
have the C-O bond length (C2-O4) in the range 1.360-1.369 A and 25 in the
˚
range 1.370-1.379 A. In addition, 32 structures have a CdN (C2-N1) bond
˚
length in the range 1.290-1.299 A.

Article
Inorganic Chemistry, Vol. 49, No. 20, 2010 9375

9376 Inorganic Chemistry, Vol. 49, No. 20, 2010
Pailloux et al.
Figure 4. Molecular structure of [NHþ4 ][(HO)(O)2PCH2C(O)N(H)-
(C6H4OH)-] NH4(7-H) (20% thermal ellipsoids).
Scheme 2
Figure 5. Molecular structure of Na{[(HO)(O)2PCH2]C7H4NO} H2O}2
3
[Na(6-H) H2O]2 (20% thermal ellipsoids).
3
˚
(O2
O3, 2.52(1) A). Additional hydrogen bond D
A
3 3 3
3 3 3
˚
approaches in the range 2.75-3.05 A are listed in the Support-
ing Information.
The Bronsted acidity of 7-H2 was evaluated by recording its
absorption spectra in aqueous NaClO4 solution as a function of
pH, and representative spectra are shown in Figure 1. The
protonation constants (pK) for 7-H2, summarized in Table 1,
are much as would be expected from the structure of the ligand,
and the values are comparable with those reported for 3-hydroxy-
phenylphosphonic acid: pK’s = 10.03, 7.24, and 1.8.45 The
first pKvalue for 7-H2 at 10.08 corresponds to deprotonation of
the phenolic hydroxyl group, and the remaining two pK values,
7.39 and 2.2, are assigned to the deprotonation of the hydroxyl
groups of the phosphonic acid fragment. The assignment of
the pK value of 10.08 for to the phenolic proton is supported by
the fact that this protonation equilibrium is accompanied by a
large change in the electronic spectrum (Figure 1). This is to be
expected since the phenolic hydroxyl is directly attached to the
aromatic ring whose π-π* transitions are being monitored in
Figure 1. The protons of the phosphonic acid group that are
involved in the second and third ionization processes are more
distant from the aromatic ring, and so, as expected, they
produce a much smaller change in the electronic spectrum.
Since we are also interested in having a water-soluble,
storable salt form of 6-H2 and 7-H2 for subsequent metal
coordination chemistry studies, we explored stoichiometric
neutralization reactions of these phosphonic acids with
NaOH and KOH in mixed MeOH/H2O solutions and in
MeOH. The reactions were performed in a manner analo-
gous to a titration experiment by addition of aqueous base
solution (0.1 M) to a MeOH solution of 6-H2 or 7-H2 or by
combination of the reactantsin MeOH solution. The reaction
mixtures were stirred at 23 °C, and the products isolated by
Figure 6. Molecular structure of Na3{[O3PCH2]C7H4NO}{[(HO)-
(O)2PCH2]C7H4NO} [Na3(6)(6-H)].
vacuum evaporation of the solvent followed by recrystalliza-
tion of the residues in various solvent combinations. Ele-
mental analyses of the residues indicate that the products are
not obtained in analytically pure form. This is due in part to
the dibasic ionization equilibria, the formation of loose
solvates, and the competing ring-opening chemistry. Unfor-
tunately, 31P NMR spectroscopy does not provide a reliable
probe for the compositional character of the salts because of
the pH dependence of the chemical shifts. The species (6-H)-
and (6)2- show similar chemical shifts (δ 11-13 ppm) that
are concentration and solvent dependent, and these are only
slightly upfield from 6-H2 in DMSO, δ 15.4. Furthermore,
the shifts for (7-H-) and (72-) fall in the same region, δ
12.5-14 ppm. Nonetheless, single crystals of the salts [Na(6-
H) H2O]2, Na3(6)(6-H) H2O, K(6-H), [K2(6)]2 3H2O, and
3
3
3
K(7-H) DMF were isolated and structurally characterized by
3
X-ray diffraction methods. The syntheses and structural data
for these compounds are discussed sequentially below. Views
of the molecules are provided in Figures 5-9, and selected
bond length data are listed in Table 3.
(44) A catalogue of structures in the Cambridge Crystallographic Data
2
˚
files provided 870 Na-N-sp bond distances that fall in a range 1.280-3.115 A
˚
For the 1:1 reactions of 6-H2 with NaOH in a mixed solvent
MeOH/H2O 3-5/1, the compound Na(6-H) was obtained in
good yield. IR spectroscopic data suggest that (6-H-) remains
in the closed-benzoxazole ring form, and the single crystal X-ray
diffraction analysis confirms this conclusion. The asymmetric
with a mean value, 2.480 A. A similar collection structure files provided 549
K-Nsp bond distances that appear in the range 2.420-3.35 A with a mean
2
˚
˚
value, 2.844 A.
(45) Martell, A. E.; Smith, R. M. Critical Stability Constant Database,
No. 46; National Institute of Science and Technology (NIST): Gaithersburg, MD,
2003.

Article
Inorganic Chemistry, Vol. 49, No. 20, 2010 9377
˚
˚
Na1-N2 2.505(1) A and Na2-N1 2.510(1) A, and five O
˚
atoms contributed by two water molecules, Na1-O9 2.448(1) A,
˚
˚
Na1-O9 (#2) 2.440(1) A, Na2-O10 2.385(1) A, Na2-O10
˚
˚
(#2) 2.540(1) A, two phosphonate groups, Na1-O7 2.319(1) A,
˚
˚
Na1-O7 (#1) 2.328(1) A, Na2-O3 2.333(1) A, Na2-O3
˚
(#4) 2.397(1) A and a bridging P-O(H) group Na1-O2
˚
˚
2.530(1) A and Na2-O6 (#5) 2.669(1) A. The Na-N distances
˚
are slightly longer than the mean distance, 2.480 A, derived
from a large collection of compounds containing sodium-sp2-
nitrogen atom interactions.44 The benzoxazole rings are planar
with identical related bond lengths in the two ring fragments,
and these are little changed from the bond lengths in the parent
acid, (6-H2). Most notable, the C2-N1and C8-N1 bond
˚
˚
lengths, 1.292(2) A and 1.401(2) A, are identical to the respec-
tive values in the parent acid. The phosphonate groups have an
asymmetric tetrahedral geometry with short, sodium coordi-
Figure 7. Molecular structure of K{[(HO)(O)2PCH2]C7H4NO} K(6-H)
(20% thermal ellipsoids).
˚
nated P-O bond lengths, P1-O3 1.487(1) A and P2-O7
˚
1.486(1) A, longer, terminal P-O bond lengths P1-O1
˚
˚
1.500(1) A and P2-O5 1.503(1) A, and P-O(H) bond lengths
˚
˚
P1-O2 1.577(1) A and P2-O6 1.586(1) A. TheP-O(H) group
is also involved in the bridge bond between the monomer units
making up the dimer.
The 2:1 reaction of aqueous NaOH solution (0.1 M) with
6-H2 in MeOH was expected to produce Na2(6). This com-
pound may form, but the only material that crystallized was
found to be Na3(6)(6-H) H2O in which the deprotonation of 6-
3
H2 is incomplete. The structure (Figure 6) contains three
unique Naþ cations, a (benzoxazole-2-ylmethyl) hydrogen
phosphonate monoanion, (6-H-), a (benzoxazole-2-ylmethyl)
phosphonate dianion, (62-), and a water molecule. Each Naþ
cation resides in a distorted octahedral coordination environ-
ment. In the cases of Na1 and Na3, the polyhedral vertices are
all occupied by oxygen atoms while for Na2 there are five
oxygen atoms and a nitrogen atom in the vertex positions. The
O-atoms surrounding Na1 are provided by an O-atom from
one (62-) ligand, Na1-O1, an O-atom from each of two (6-
H-) anions, Na1-O6 and Na1-O7 #1, two O-atoms from an
asymmetric bidentate P, O, O bonded (6-H-) anion, Na1-O6
#2 and Na1-O8 #2(H), and an O-atom from a water molecule,
Na1-O9, that bridges this unit to Na3. For Na3, the O-atoms
are provided by the bridging water molecule O9, two O-atoms
from a symmetric bidentate P, O, O bonded (6-H-) anion,
Na3-O7 #2 and Na3-O8 #2(H), and three O-atoms from
three (62-) dianions, Na3-O2, Na3-O3 #3 and Na3 #01 #5.
The Na-O (water) bond lengths are quite different: Na1-O9
Figure 8. Molecular structure of [K2{[O3PCH2]C7H4NO}]2 3H2O
3
[K2(6)]2 3H2O (20% thermal ellipsoids).
3
˚
˚
2.501(2) A and Na3-O9 2.345(2) A. The Na-O(P) bond
˚
lengths fall in the ranges Na1 2.306(2)-2.413(2) A (avg. 2.363
˚
˚
˚
A) and Na3 2.327(2)-2.821(2) A (avg. 2.485 A). The Na-
O(H)P bond lengths, as expected, are longer: Na1-O8 #2(H)
Figure 9. Molecular structure of [Kþ][(HO)(O)2PCH2C(O)N(H)-
˚
˚
(C6H4OH)-], K(7-H) DMF (20% thermal ellipsoids).
2.957(2) A and Na3-O8 #2(H) 2.856(2) A. The O-atoms
3
coordinated to Na2 originate from P-O groups in four (62-
)
unit (Figure 5) contains two Naþ cations, two water molecules,
and two bidentate chelating hydrogen phosphonate anions,
(6-H)-. The chelate interaction employs one phosphonate
oxygen atom and the N atom of the intact benzoxazole ring
fragment. The unit cell is composed of infinite chains of dimers
formed along the b axis via Na-O(H)P-O(molecule 1)-Na-
(molecule 2) linkages. These chains are weakly associated
above and below via hydrogen bonding of water molecules
along the a axis. The Naþ cations have distorted six coordinate
coordination polyhedra with the polyhedron around Na2 more
distorted than that around Na1. The vertices of the polyhedra
are occupied by one N atom from a benzoxazole fragment,
dianions and a P-O(H) group O-atom in a (6-H-) ligand. The
last coordination position is provided by the N-atom of a
-
˚
bidentate (6-H ) anion. The Na2-N2 distance, 2.586(2) A, is
longer than the value in [Na(6-H) H2O]2 suggestive of only a
3
weak sodium-benzoxazole ring N-atom interaction.44 The
˚
range of Na2-O(P) bond lengths is 2.303(2)-2.588(2) A
(avg. 2.430 A). The benzoxazole ring fragments in (62-) and
˚
(6-H-) are planar and each phosphorus atom is pseudo-
tetrahedral. The P-O and P-C bond lengths in the (6-H-)
anion of Na3(6)(6-H) H2O are similar to those found in the 1:1
3
˚
[Na(6-H) H2O]2 structure: P2-O6 1.504(2) A, P2-O7
1.497(2) A, P2-O8(11) 1.580(2) A and P2-C9 1.818(2) A.
3
˚
˚
˚

9378 Inorganic Chemistry, Vol. 49, No. 20, 2010
Pailloux et al.
There are distinct changes, however, in the (62-) fragment. Two
and O3), one bidentate O, O bound (62-) dianion (O1 #2 and
O4 #2), one O bound (62-) dianion, and a water molecule. It is
noted that the benzoxazole ring O-atom, which is normally
coordination silent in complexes formed with transition metal
of the P-O bond lengths are essentially identical to the shorter
-
˚
˚
distances in (6-H ):P1-O1 1.514(2) A and P1-O2 1.508(2) A,
˚
but the third P-O bond length, P1-O3 1.548(2) A, is much
shorter as a result of the loss of the proton. Lastly, the P1-C1
and lanthanide cations, is 3.105(1) A from a Kþ cation. This
˚
˚
bond length, 1.861(2) A, is significantly elongated compared to
may indicate a very weak K-Oring interaction. The nearest
neighbors around K2 are provided by one bidentate phos-
phonate ligand (O2 and O3), one water molecule, and mono-
dentate interactions with three additional (62-) dianions.
During the course of the studies of the KOH/6-H2 neu-
tralization reactions it was noted that combination of the
reagents under more dilute conditions (final solution pH ∼4)
led to a crystalline solid following recrystallization from
DMF. Subsequent single crystal X-ray diffraction analysis
P2-C9.
Stoichiometric 1:1 reactions of KOH and 6-H2 in MeOH/
H2O mixtures and in pure MeOH, performed by slow
combination of the reactants, produce solid residues that
display a single 31P NMR resonance at δ 12.4 in MeOH.
Unfortunately, single crystals were not obtained from these
samples. The 2:1 combinations of KOH and 6-H2 were then
explored in MeOH/H2O solvent mixtures. Solid residues
were obtained following solvent evaporation, and these were
dissolved in MeOH/CH3CN solution, filtered, and allowed
to slowly evaporate. Crystals were not obtained; however,
extraction of the solids with DMF led to partial dissolution.
The soluble fraction was evaporatedto dryness, recrystallized
from MeOH/DMF mixtures and single crystals were ob-
tained. X-ray diffraction analysis revealed that this com-
pound is the salt K(6-H). A view of the environment around
K1 is shown in Figure 7. The asymmetric unit contains a Kþ
cation and a 6-H- anion and the Kþ cation resides in a
distorted octahedral coordination environment with vertices
occupied by five oxygen atoms (O3, O4, O2 #1, O2 #2, O3 #3)
and a nitrogen atom (N1 #1). The O2 #1 and N1 #1 atoms are
provided by a molecule of 6-H- that binds in a bidentate
revealed formation of another salt, K(7-H) DMF. A view of
3
the molecule is shown in Figure 9. The starting (benzoxazol-
2-ylmethyl)phosphonic acid 6-H2 has undergone ring-opening
in a fashion noted earlier, vide supra. The Kþ can be considered
to reside in a distorted monocapped trigonal prismatic
coordination polyhedron. The trigonal face positions are
˚
occupied by the oxygen atoms O1(H) (K1-O1 3.180(2) A),
˚
˚
O1#1(H) (K1-O1#1 3.170(2) A), O4(P) (K1-O4 2.762(2) A)
˚
and O6 #1(K1-O6 #1 2.750(2) A). The O6 and O6 #1 atoms
originate from the disordered DMF solvent molecules. The
˚
seventh O atom, O3#2 (K1-O3#2 2.831(2) A), belongs to a
P-O(H) group in a third molecule of (7-H-). The relatively
long K1-O1 and K1-O1 #1 distances areconsistent with the
phenol group acting only as a very weak donor toward the
potassium cation.
˚
fashion; the K1-O2 #1 bond length, 2.6995(7) A, is the
shortest of the K-donor atom bond lengths. The K1-N1 #1
The lanthanide ion coordination chemistry of 6-H2 and
7-H2 is of interest, and numerous attempts were made to
isolate and crystallize 1:1 and 2:1 ligand/Ln(III) complexes.
Although it is apparent that complexes form, none were
obtained analytically pure or as X-ray diffraction quality
single crystals. However, titration of 1:1 mixtures of 7-H2 and
La(III), Nd(III), and Gd(III) in 0.1 M NaClO4 solution as a
function of pH were performed, and complex formation was
monitored by UV-vis spectrophotometry (Figure 2). The
spectra resemble those obtained from the free ligand alone
(Figure 1). In particular, it is observed that the first proton-
ation constant of 7-H2, in the presence of Ln(III) ions, is
essentially unchanged. Therefore, it is concluded that the
phenolic oxygen atom is probably not coordinating or only
weakly coordinating to the Ln(III) ions. This is consistent with
bond length is 2.8874(9) A.44 A second 6-H- anion bonds to
˚
the Kþ as an asymmetric bidentate phosphonate with
˚
˚
K1-O3 2.8961(7) A and K1-O4 2.850(8) A. The remaining
two O-atoms in the coordination sphere are O2 #2 and O3 #3,
˚
˚
with K-O bond lengths of 2.7228(8) A and 2.8453(8) A,
respectively. The P-atom geometries in the benzoxazole
fragments are distorted tetrahedral with P-O bond lengths
in the range 1.4918(7)-1.5678(7) A. The benzoxazole rings
are planar, and the bond lengths are similar to those in
˚
[Na(6-H) H2O]2.
3
The DMF insoluble fraction from the 2:1 KOH/6-H2
reaction was dissolved in hot MeOH, and the solution allowed
to slowly cool. This provided single crystals of a second
complex, and X-ray diffraction analysis revealed the structure
of the expected 2:1 potassium complex, [K2(6)]2 3H2O. A view
the structure of K(7-H) DMF described above. In contrast,
3
3
of the molecule is shown in Figure 8. The asymmetric unit
contains two Kþ cations, one phosphonate dianion (62-), and
11/2 water molecules. Each Kþ can be considered to reside
in a highly distorted octahedral coordination environment in
which the vertices for K1 are N1, O3, O1 #2, O4 #2, O6 #3, and
O2 #1 and for K2 are O2, O3, O4 #2, O2 #4, O3 #5, and O5 #6.
The range of K-O bond lengths involving K1, 2.676(9)-
the equilibrium corresponding to the second protonation
constant (pK2) of the ligand is moved to lower pH as a result of
competition between the proton and the metal ion for the
anionic form of the ligand. From these equilibria, the formation
constants were calculated, and the log K(MLH) values are
summarized in Table 1.21 A continuous variation analysis
(Job’s method) was also performed by varying the ratio of La3þ
to 7-H2 at pH 6.0 with{[La3þ] þ [L]} = 2 ꢀ 10-5 M, and this
confirmed the proposed 1:1 metal/ligand complex stoichio-
metry. It is of interest that the log K(MLH) values for the
formation of the Ln(LH)þ1 complexes (LH2- = 72-) are very
similar or decrease slightly going from La(III) to Gd(III). This
is rather unusual since the stability of most lanthanide com-
plexes increase significantly progressing from the lighter, larger
ions to the heavier, smaller ions.45
˚
˚
3.105(9) A (avg. 2.828 A) is slightly greater than the range of
˚
K-O bond lengths around K2: 2.714(9)-2.944(9) A (avg.
˚
˚
2.721 A). The K1-N1 bond length is fairly long, 3.016(9) A,
but still within the range observed in a collection of structures
containing K-Nsp2 interactions.44 The longest K1-O bond
˚
length, K1-O6 #3, 3.105(9) A, involves a potassium-water
interaction. If this water is removed from the coordination
sphere, leaving a five coordinate K1, then the range and
average K-O distances about K1 and K2 become nearly
identical. The six nearest neighbor atoms around K1 are
provided by one bidentate N, O bound (62-) dianion (N1
Since we were unable to grow single crystals of Ln(III)
complexes containing 7-H- or 72-, one can only speculate
on the structures of complexes based upon related systems.

Article
Inorganic Chemistry, Vol. 49, No. 20, 2010 9379
For example, lanthanum(III) complexes with phenylphosphonic
acid and benzylphosphonic acid, [ArP(O)(OH)2], have been
isolated and structurally characterized.46 The complexes,
La[O3PAr][O2(HO)PAr], contain both a dianionic ligand
and a monoanionic ligand each bonded in a bidentate mode
to La(III) through two of the phosphonic acid oxygen atoms.
This results in four-membered La-O-P-O chelate rings.
A rule of ligand design47 indicates that four-membered chelate
rings have a minimum steric strain with the largest metal ions.
One could thus speculate that the small change in log K from
La(III) to Gd(III) reflects a balancing of decreasing metal ion
size and increasing steric requirements of the four-membered
chelate ring formed by the anionic ligand. As mentioned
above, the log K values obtained for the Ln(III) ions with
7-H2 (Table 1) suggest that the phenolic group of the ligand is
not coordinated to the metal ion, or at best is only weakly
coordinated. This suggestion was examined further for a 1:1
complex fragment, [La(7)þ1], by MM (molecular mechanics)
calculation48 using the program HyperChem.49 Such calcula-
tions using the default MM parameters, which include param-
eters for La(III), indicate a very high strain structure if the
phenolic oxygen is coordinated to the Ln(III) ion. This is not
unexpected as such coordination would involve formation of
an energetically unfavorable 7-membered chelate ring, re-
quiring considerable distortion of the 7-H2 ligand. The
calculated low strain structure generated by MM calculation
formed with a non-coordinating and protonated phenolate
group is shown in Figure 10. This structure features an
asymmetric tripodal chelate interaction on La(III) by a 72-
ligand binding through two La-O-P interactions and a
La-OdC amide bond. Completion of charge neutralization
might occur with a 7-H- ligand (bound or unbound with
La(III)) or by an appropriate simple anion, for example,
ClO4- or NO3-. The inner sphere coordination polyhedron
of the computed cationic species was completed by addition
Figure 10. Proposed structure of a 1:1 complex [La(7)]þ1 {[LLH]þ1 in
Table1}.
of water molecules. Lastly, it is noted that attempts to mea-
sure log K(MLH) for the formation of the Lu(III) complex with
7-H2 were prevented by precipitation of Lu(OH)3 before
significant complex-formation had occurred. This supports
the idea that log K(MLH) for Lu(III) with 7-H2 is even lower
than for the larger Ln(III) ions such as La(III), Nd(III), and
Gd(III).
Conclusion
A convenient three step synthesis for the (benzoxazol-2-yl
methyl)phosphonic acid, 6-H2, has been developed, and its
subsequent ring-opening to give [(2-hydroxyphenylcarbamoyl)
methyl]phosphonic acid, 7-H2, has been observed. Both phos-
phonic acids provide interesting possibilities as multifunctional
ligands toward p-, d-, and f-block metal cations. It was desired
to have well-defined Group 1 salts of 6-H2 as reagents for meta-
thetical syntheses of metal complexes; therefore, the neutraliza-
tion reactions of 6-H2 with NaOH and KOH were examined.
These reactions revealed that the anions (6-H-) and (62-) form
complicated extended structures with Naþ and Kþ cations.
Further work is in progress that will reveal the coordination
features of the phosphonates in complexes formed with alkaline
earth, heavy p-block and f-block cations.
(46) Wang, R.-C.; Zhang, Y.; Hu, H.; Frausto, R. R.; Clearfield, A.
Chem. Mater. 1992, 4, 864.
(47) Hancock, R. D.; Martell, A. E. Chem. Rev. 1989, 89, 1875.
(48) Hancock, R. D. Acc. Chem. Res. 1990, 26, 875.
(49) HyperChem program, version 7.5; Hypercube, Inc.: Waterloo, Ontario,
N2l 3X2, Canada.
Supporting Information Available: Selected NMR spectra for
7-H2 and CIF files for the crystal structures. This material is
available free of charge via the Internet at http://pubs.acs.org.