Structural analogues of bioactive phosphonic acids: First crystal structure characterization of phosphonothioic and boranophosphonic acids

Article abstract of DOI:10.1080/10426500701852760

Phosphonothioic and boranophosphonic acids have been structurally characterized for the first time by single X-ray crystallography. These two functional groups, and the corresponding phosphonic acid, were all conveniently synthesized in high yields from t

Full text of DOI:10.1080/10426500701852760

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Structural Analogues of
Bioactive Phosphonic Acids:
First Crystal Structure
Characterization of
Phosphonothioic and
Boranophosphonic Acids
Yamina Belabassi a , Audra F. Gushwa a , Anne F.
Richards a & Jean-Luc Montchamp a
a Department of Chemistry , Texas Christian
University , Fort Worth, Texas, USA
Published online: 12 Aug 2008.
To cite this article: Yamina Belabassi , Audra F. Gushwa , Anne F. Richards & Jean-
Luc Montchamp (2008) Structural Analogues of Bioactive Phosphonic Acids: First
Crystal Structure Characterization of Phosphonothioic and Boranophosphonic Acids,
Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9, 2214-2228, DOI:
10.1080/10426500701852760
To link to this article: http://dx.doi.org/10.1080/10426500701852760
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Phosphorus, Sulfur, and Silicon, 183:2214–2228, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701852760
Structural Analogues of Bioactive Phosphonic Acids:
First Crystal Structure Characterization of
Phosphonothioic and Boranophosphonic Acids
Yamina Belabassi, Audra F. Gushwa, Anne F. Richards,
and Jean-Luc Montchamp
Department of Chemistry, Texas Christian University, Fort Worth,
Texas, USA
Phosphonothioic and boranophosphonic acids have been structurally characterized
for the first time by single X-ray crystallography. These two functional groups, and
the corresponding phosphonic acid, were all conveniently synthesized in high yields
from trityl H-phosphinic acid (Ph3CPO2H2). The resulting trityl-substituted series:
Ph3CP(O)(OH)2, Ph3CP(S)(OH)2, Ph3CP(O)(BH−)(OH)]LH+ (L = Lewis base) is
fully characterized by spectroscopic methods, and3the structural characteristics are
compared. The results indicate that boranophosphonic acids should be investigated
anytime a bioactive phosphonic acid has been identified. The solid state arrange-
ments of the synthesized compounds are also discussed.
Keywords Boranophosphonic acid; H-phosphinic acid; phosphonic acid; phosphonoth-
ioic acid; solid state; X-ray diffraction
INTRODUCTION
Phosphonic acids are an important class of organophosphorus com-
pounds. Numerous biologically-active molecules contain this moiety1
and various analogues have been evaluated as phosphonic acid replace-
ments in bioactive compounds. Both boranophosphonic acids2 and phos-
phonothioic (thiophosphonic) acids3 have potential or demonstrated
bioactivities; phosphonothioic acids have often been employed as phos-
phatase inhibitors, and recently boranophosphonic acids have been
Received 3 December 2007; accepted 9 December 2007.
Financial support of this research by The Robert A Welch Foundation (P0176, AFG,
AFR), and by the National Institute of General Medical Sciences/NIH (1R01GM067610,
YB, JLM) is gratefully acknowledged.
Address correspondence to Jean-Luc Montchamp, Department of Chemistry, TCU
Box 298860, Texas Christian University, Fort Worth, Texas 76129, USA. E-mail:
j.montchamp@tcu.edu
2214

Phosphonothioic and Boranophosphonic Acids
2215
SCHEME 1 Synthesis of compounds 2–5: (a) O3, MeOH, 0◦C, 82%; (b) N,O-
bis(trimethylsilyl)acetamide, THF, RT, 1h; (c) S8, RT, then MeOH; (d) BH.3Me2S,
RT, then MeOH; (e) BH.3EtNiPr2, then NH4OH, MeOH.
introduced in search of antiviral activity.2 Furthermore they might be
useful motifs in boron neutron capture therapy (BNCT).4 Considering
their importance it is surprising that, to the best of our knowledge, no
X-ray crystal structures have been reported for compounds containing
either functional group.5
RESULTS AND DISCUSSION
Synthesis
Herein, we report the synthesis, structural characterization, and com-
parison, of trityl phosphonic 2, phosphonothioic 3, and boranophospho-
nic acids 4 and 5. All four compounds are prepared from facile syn-
theses from the known trityl-H-phosphinic acid 16 in excellent yields
(Scheme 1). To enable structural comparisons and to allow the intro-
duction of various functionalities we employed a divergent synthetic
approach for all three functional groups from 1, thus providing addi-
tional examples of the utility of H-phosphinic acids in organophospho-
rus chemistry.7Simple oxidation of 1 with ozone8 delivered 2 cleanly.
Silylation of 1 and trapping of the resulting phosphonite with ele-
mental sulfur, or with borane-dimethylsulfide complex, followed by
methanolysis, afforded 3 and 4, respectively. The boranophosphonic
acid salt 5 was obtained analogously to 4, but using BH.3DIEA fol-
lowed by treatment with methanolic ammonium hydroxide.2 Trityl
phosphonic acid is typically made by reaction of triphenylmethanol with
PCl3 followed by hydrolysis.9,10 Phosphonothioic acids have been pre-
pared on occasion from H-phosphinic acids through silylation followed

2216
Y. Belabassi et al.
FIGURE 1 X-ray structure of Ph3CP(O)(OH)2 2. Selected bond distances
˚
(A) and angles (deg): P(1)-O(3), 1.5070(10); P(1)-O(1), 1.5386(10); P(1)-O(2),
1.5518(11); P(1)-C(1), 1.8588(14); O(3)-P(1)-O(1), 111.36(6); O(3)-P(1)-O(2),
112.41(6); O(1)-P(1)-O(2), 108.29(6); O(3)-P(1)-C(1), 110.73(6); O(1)-P(1)-C(1),
105.90(6).
by trapping with elemental ulphur,11 or more generally via multistep
pathways.12
The crystal structures of compounds 2–5 are shown in Figures 1–4.
Although phosphonic acid 2 is a well-known and widely used compound9
its crystal structure has not been reported and is included to allow struc-
tural comparisons to be drawn. Compound 2 has a P O bond length of
˚
˚
1.5070(10) and P OH bond lengths of 1.5386(10) A and 1.5518(11) A.
Although phosphonic acids have been structurally characterized, data
are limited. But these values compare well with those observed in t-
butyl phosphonic acid that has a P O bond length of 1.5083(16) and
13
˚
˚
˚
P OH bond lengths of 1.5544(17) A and 1.5448(16) A. Not surpris-
ingly, the P S bond in 3 is much longer (1.9513(9) A). The P-B bond

Phosphonothioic and Boranophosphonic Acids
2217
FIGURE 2 Crystal structure of Ph3CP(S)(OH)2 3, the first structurally char-
˚
acterized example of a thiophosphonic acid. Selected bond distances (A) and
angles (deg): P(1)-S(1), 1.9513(9); P(1)-O(1), 1.560(2); P(1)-O(2), 1.565(2); P(1)-
C(1), 1.884(3); O(1)-P(1)-O(2), 101.88(11); O(1)-P(1)-C(1), 105.76(11); O(2)-P(1)-
S(1), 113.44(8); C(1)-P(1)-S(1), 114.30(8).
˚
in 4 at 1.89(5) A is slightly longer than in a PhP(BH3)(OR)2 compound
14
˚
(1.851(6) A), and essentially the same as in the boranophosphates,
(MeO)2P(O)BH−/i-Pr2NH+ (1.887(3) A),
and (MeO)2P(BH3)OK
15
˚
3
2
(1.895(6) A).16 For all compounds, the P O single bonds are similar and
range from 1.560(2)-1.60(3) A. The P C bond lengths increase slightly
from 2 to 5 (1.8588(14)-1.9212(17) A). It is interesting to note that phos-
˚
˚
˚
phonothioic compound 3 exists in solution and in the crystalline state,
only as the thiono P( S)OH tautomer and not the thiolo P( O)SH tau-
tomer, consistent with the structure usually assumed to predominate
in this equilibrium when a C P bond is present.3
Compounds 2–5 were also fully characterized by IR, mass spectrom-
etry, and NMR spectroscopy. The 31P NMR chemical shifts in CDCl3
are: 1, 40.9 ppm; 2, 32.7 ppm; 3, 92.5 ppm; 4, 108.1 ppm (93.3 ppm in
water at pH 11.2, similar to other reported boranophosphonate salts2);
and 5, 108.0 ppm. The very large downfield shift in 3 versus 2 upon

2218
Y. Belabassi et al.
FIGURE 3 Crystal structure of 4, the first structurally characterized example
˚
of a boranophosphonic acid. Selected bond distances (A) and angles (deg): P(1)-
O(1), 1.53(3); P(1)-O(2) 1.60(3); P(1)-B(1) 1.89(5); P(1)-C(1), 1.91(4); B(1)-H(1),
1.2(6); O(1)-P(1)-O(2), 108.9(16); O(1)-P(1)-B(1), 115(2); O(2)-P(1)-B(1), 106(2);
O(1)-P(1)-C(1), 107.9(17); O(2)-P(1)-C(1), 104.4(16); B(1)-P(1)-C(1), 114(2).
replacement of the oxygen with sulfur is typical.17 The signals for bo-
ranophosphonates 4 and 5 are consistent with literature values indi-
cating phosphoryl character, and less as a bonding description as a
P(III) borane complex.14 The almost identical 31P NMR chemical shifts
observed with 4 and 5 support the solid-state structural analogy be-
tween the two compounds. Boranophosphonate 4 has a formally nega-
tively charged boron atom, as would be expected for the representation
RP(+)(BH−)(OH)2. Despite careful examination of the residual electron
density m3ap, locating the hydrogen for O(1) proved unsuccessful. It is
likely that the hydrogen atom is disordered or located between the phos-
phonate oxygen and lattice ethanol, with significant ionization of one
OH bond in 4 (Scheme 2). Indeed, one of the P O bond is shortened
significantly, and in the range of a formal phosphoryl P O group.18 To
clarify this, 5 was prepared and structurally characterized. The hydro-
gen atoms on the amine nitrogen N(1), and the phosphorus oxygen O(2),
were located from the difference map. Comparison of bond lengths and

Phosphonothioic and Boranophosphonic Acids
2219
˚
FIGURE 4 Crystal structure of 5. Selected bond distances (A) and angles
(deg): P(1)-O(1), 1.5218(12); P(1)-O(2), 1.5953(15); P(1)-B(1), 1.920(3); P(1)-
C(1), 1.9212(17); B(1)-H(4); 1.07(3); O(1)-P(1)-O(2), 108.55(8); O(1)-P(1)-B(1),
116.91(10); O(2)-P(1)-B(1), 106.13(11); O(1)-P(1)-C(1), 108.45(7); O(2)-P(1)-C(1),
102.17(8); B(1)-P(1)-C(1), 113.47(10); P(1)-B(1)-H(2), 108.8(17).
angles show excellent structural agreement with 4. This indicates that
RP(+)(BH−3 )(OH)2 is a much stronger acid than 2, and therefore 4 is
better represented as RP(O)(BH−3 )(OH)H+, where partial protonation
of lattice ethanol is probably occurring, and P O bond character is very
pronounced (Scheme 2). The P B bond in 4 is also intermediate be-
tween that of PhP(BH3)(OR)2 and (MeO)2P(O)BH−, but closer to the
3
latter.
M.p. The measured pKas for 2 are 5.6 and 9.8, and for 3 are 4.4 and
8.9, confirming the previously observed lower pKas for phosphonothioic
acids versus the corresponding phosphonic acids. The only measurable
pKa for 4 was 5.9. This was independently verified by titrating 5, sug-
gesting that the first pKa for boranophosphonates is much lower than
in 2 and 3, also in agreement with the X-ray data. Some decomposi-
tion of 4 (∼10%) leading to the H-phosphinate salt of 1 is observed
at high pH. Structural studies of boranophosphates15,16,20 have shown
that although the P B bond is much longer than in the correspond-
ing phosphate, the compounds are good phosphate mimics and capa-
ble of entering an enzyme active site, much like phosphonothioates.
Similarly, the structural data of boranophosphonate 4 indicate good
mimicry for a phosphonate, in spite of the long P-B bond. Therefore,

2220
Y. Belabassi et al.
SCHEME 2 Bonding representations and structural comparisons for 4 and 5.
boranophosphonates might be useful pharmacophores, although there
are limited studies currently available.2
Discussion of the Solid-State Arrangement of 2–5
Phosphinic and phosphonic acids are known to form strong hydrogen
bonds and can act simultaneously as proton donor and acceptor. Phos-
phinic acids usually dimerize20 or form one-dimensional polymers,21
while phosphonic acids typically crystallize as polymeric aggregates.22
In the solid state, the trityl phosphonic acid, 2, adopts a motif in which
the molecules are interlinked by hydrogen bonds to the solvent lattice
molecules, for example, H(8)-O(5) are H-bonded at a distance of 1.567,
and H(1)-O(4) at 1.675 (Figure 5). The phosphonothioic acid, 3, has a dif-
ferent packing arrangement compared with 2, 4 and 5. Here, H-bonding
to the acetone (solvent) occurs but no intermolecular phosphonic pack-
ing is observed (Figure 6).
M.p. Complexes 4 and 5 exhibit similar structural arrangements.
Each P O and P OH oxygen atoms participate in hydrogen bonding,
the P OH group H bonds to P O affording dimeric interactions as de-
picted in Figures 7–9. In 4 the lattice solvent molecules show little
intermolecular interaction with the phosphonic acid and are present to
fill the voids in the crystal lattice. However, in 5, the protonated amine
occupies a position between two phosphonic acid moieties allowing O(1)
(P O) to form a second hydrogen bond with the amine proton (N H).

Phosphonothioic and Boranophosphonic Acids
2221
FIGURE 5 Packing Diagram of 2.
This double hydrogen accepting of P O results in weaker hydrogen
bonding,23 which is confirmed through the O..O intermolecular separa-
tions of 4 and 5. The measured intermolecular O..O bond lengths and
O-H..O angles that characterize the H-bond strength are found to be
2.573/151.41 for 4 and 2.710 /151.41 for 5. These values are consistent
with corresponding literature values.13,24
FIGURE 6 Solid-State Arrangement of 3.

2222
Y. Belabassi et al.
FIGURE 7 Packing Diagram of 5.
EXPERIMENTAL
General Chemistry
1H NMR spectra were recorded on a Varian Mercury-300 spectrometer.
Chemical shifts for 1H NMR spectra are reported (in parts per million
[ppm]) relative to internal tetramethylsilane (Me4Si, δ = 0.00 ppm) with
CDCl3 or DMSO-d6 as solvent. 13C NMR spectra were recorded at 75
MHz. Chemical shifts for 13C NMR spectra are reported (in parts per
million) relative to CDCl3 (δ = 77.0 ppm) or to DMSO-d6 (δ = 40.0 ppm).
31P NMR spectra were recorded at 121 MHz on a Varian Mercury-300
spectrometer and chemical shifts reported (in parts per million) rela-
tive to external 85% phosphoric acid (δ = 0.0 ppm). Mass spectrometry
was provided by the the Mass Spectrometry Facility of the University
of South Carolina. Organic solutions of products were dried over anhy-
drous MgSO4.
Reagents and Solvents
Triphenylmethanol was purchased from TCI, N,O-bis(trimethylsilyl)
acetamide was purchased from Gelest, Inc., Borane-N, N-diisopropyl-
ethylamine complex was purchased from Aldrich, Borane-methyl

Phosphonothioic and Boranophosphonic Acids
2223
FIGURE 8 Diagram showing H-bonding between the ions in 5.
sulfide complex was purchased from Alrdich, aqueous hypophospho-
rous acid (50 wt.%) was obtained from Aldrich, and all were used as
received. Anhydrous THF was freshly distilled from NaH and benzophe-
none prior to use. All other reagents were used as received. Reagent or
HPLC grade solvents (toluene and MeOH) were used throughout this
study and were not dried prior to use.
Trityl H-Phosphinic Acid 1
A mixture of triphenylmethanol (100 g, 384 mmol), aqueous H3PO2
(845 mmol) and toluene (770 mL) was prepared at room temperature.
The resulting mixture was heated at reflux under N2 for 12 h with con-
tinuous water-removal using a Dean-Stark trap. The reaction was mon-
itored by 31P NMR. The reaction mixture was concentrated under vac-
uum, the residue was partitioned between CH2Cl2 and H2O, the organic
phase was separated and the aqueous layer was extracted with CH2Cl2.
The combined organic extracts were washed with brine, dried over
MgSO4 and concentrated. The resulting residue was diluted in EtOAc

2224
Y. Belabassi et al.
FIGURE 9 Packing diagram of 4.
and washed several times with EtOAc, afforded the H-phosphinic acid
(44 g, 37%) as a white powder by simple vacuum filtration. M.p. 207–
210◦C.
IR (KBr) 3420.4 (OH), 3086.5-3021.8 (CH), 1180.0 (P O), 980.4
1
(P OH) cm−1; H NMR (CDCl3) δ 10.37 (s, 1H), 7.48 (1 J = 572 Hz,
PH
1H), 7.3–7.1 (m, 15H, ArH); 13C NMR (75.45 MHz, CDCl3) δ 57.1, 126.5,
2
3
127.6, 128.5, 128.6, 129.7, 130.6 (d, J
= 28 Hz), 140.1(d, J
=
PCC
PCCC
13 Hz); 31P NMR δ 40.9 (d, 1 J = 572 Hz); HRMS (FAB) calcd. For
PH
C19H17O2P, (M) 308.0966, found 308.0959.
Tritylphosphonic Acid 2
Ozone was bubbled into a solution of trityl-H-phosphinic acid5 (500
mg, 1.62 mmol) in MeOH (25 mL), at 0◦C. After 3 h, the ice bath
was removed and N2 was bubbled into the reaction mixture for 2 h.
The white precipitate was removed via centrifugation. The filtrate was
concentrated in vacuo, and the residue partitioned between EtOAc and

Phosphonothioic and Boranophosphonic Acids
2225
brine. The aqueous layer was extracted with EtOAc (3x). The combined
organic extracts were dried over MgSO4 and concentrated to afford 2
(431 mg, 82%) as a white solid. M.p. 248–250◦C. IR (KBr) 2800.0 (OH),
1
1142.6 (P O), 965.7 (P OH) cm−1; H NMR (CDCl3) δ 7.26–7.18 (m,
15H, ArH), 4.12 (bs, 2H, OH); 13C NMR δ 61.2 (d, 1 J = 141 Hz),
PC
127.3, 128.2, 130.5 (d, 3 J
= 7 Hz), 141.2 (d, 2 J
= 5 Hz); 31P NMR
PCCC
PCC
δ 32.7 (s); HRMS (ES) calcd. For C19H17O3P, (M H) 323.0837, found
323.0843. Crystals of 2 were obtained from MeOH.
Trityl Phosphonothioic Acid 3
A solution of 1 (462 mg, 1.5 mmol) in anhydrous THF (15 mL) under
N2, was treated with BSA (1.85 mL, 7.5 mmol) at room temperature
(RT) for 1 h. Sulfur (96 mg, 3 mmol) was then added at RT, and the
mixture stirred for 1 h. After addition of MeOH (15 mL), the mixture
was stirred for 2 h, then concentrated in vacuo. The residue was diluted
in MeOH, giving a heterogeneous mixture. A precipitate was separated
from the yellowish filtrate via centrifugation. The filtrate was concen-
trated in vacuo, affording 3 (510 mg, 100%) as a pale yellowish solid.
M.p. 84–89◦C. IR (KBr) 3327.5 (OH), 3174.6 (OH), 949.8 (P OH), 700.1
1
(P S) cm−1; H NMR (DMSO-d6) δ 7.33–7.10 (m, 15H, ArH), 6.69 (bs,
2H, OH); 13C NMR δ 126.9, 127.9, 129.0, 129.7, 131.1 (d, 3 J
= 6
PCCC
Hz), 144.5 (d, 2 J
= 5 Hz); 31P NMR δ 92.5 (s); HRMS (ES) calcd.
PCC
For C19H17O2PS, (M-H) 339.0609, found 339.0616. Crystals of 3 were
obtained from toluene/CH2Cl2/MeOH (6:3:1).
Trityl Boranophosphonic Acid 4
A solution of 1 (308 mg, 1 mmol) in anhydrous THF (15 mL) was
treated with BSA (1.23 mL, 5 mmol) at RT for 1 h, under N2. A solution
of BH3.Me2S (1 mL, 2.0 M solution in THF) was then added at RT, and
the resulting mixture stirred for 1 h. After addition of MeOH (15 mL),
the mixture was stirred for 2 h, then concentrated in vacuo. The residue
was partitioned between CHCl3 and H2O and the organic phase was
washed with H2O (3x). The combined aqueous layers were concentrated
in vacuo, affording 4 (319 mg, 99%) as a white powder. M.p. 119–122◦C.
IR (KBr) 3421.1 (OH), 3173.9 (OH), 2356.3 (BH), 1040.4 (PO2H), 702.0
1
(P-B) cm−1; H NMR (DMSO-d6) δ 7.36–7.11 (m, 15H, ArH), 6.7 (bs,
2H, OH), 2.59 (bq, J = 7 Hz, 2H, CH ), 1.10 (bt, J = 7 Hz, 3H, CH );
2
3
13C NMR δ 125.9, 127.5, 131.5 (d, 3 J
= 4 Hz), 146.2; 31P NMR δ
PCCC
108.1 (bs). HRMS (ES) calcd. For C27H39BNO2P, (M-) 321.1216, found
321.1216. Crystals of 4 were obtained from CH2Cl2/EtOH.
Trityl Boranophosphonic Acid Diisopropylethylamine Salt 5
1 (481 mg, 1.56 mmol) in anhydrous THF (20 mL) was treated
with BSA (1.92 mL, 5 mmol) for 1 h at RT under N2. A solution of

2226
Y. Belabassi et al.
DIPEA.BH3 (543 µL, 3.12 mmol) was then added at RT. After 1 h, conc.
NH4OH in MeOH (20 mL, 1:1, v/v) was added, stirring continued for
1 h, then concentrated in vacuo. The residue was partitioned between
CHCl3 and H2O, and the organic phase was washed with H2O (3x).
The combined organic layers were dried over MgSO4, filtered and con-
centrated in vacuo, affording 5 (660 mg, 94%) as a white powder. M.p.
104–107◦C. IR (KBr) 3440.2 (OH), 3379.3 (NH), 2371.5 (BH), 2329.7
1
(PO2), 1105.1 (C-N), 1032.8 (P OH), cm−1; H NMR (CDCl3) δ 7.46–
7.11 (m, 15H, ArH), 3.53 (sept, J = 7 Hz, 2H, CH(CH3)2), 2.83 (q, J=
7 Hz, 2H, CH ), 2.35 (s, OH), 1.26-1.21 (m, 15H, CH ); 13C NMR δ 12.2,
2
3
41.7, 53.0, 66.1 (d, 1 J = 29 Hz), 126.0, 127.5, 131.5 (d, 3 J
= 5
PC
PCCC
Hz), 144.8; 31P NMR δ 109 (q, J = 133 Hz); HRMS (ES) calcd. For
PB
C27H39BNO2P, (M-) 321.1216, found 321.1224. Crystals of 5 were ob-
tained from toluene/CH2Cl2/MeOH (6:3:1).
Crystallographic Parameters
Thermal Ellipsoids at 50% probability, H atoms on the phenyl groups
have been omitted for clarity. Crystal Data for complexes 2–5:25 (2)
˚
C21H25O5P (M = 388.38), T = 213(2) K, Triclinic, P-1, a = 9.0901(6) A,
◦
◦
˚
˚
b = 9.7482(6) A, c = 12.3042(7)A, α = 94.8300(10) , β = 108.3390(10) ,
γ = 105.2350(10)◦, Z = 2, Reflections Collected = 6210, Independent
reflections = 4416, R (int) = 0.0143, Final R indices [I > 2σ(I)] R1 =
0.0376, wR2 = 0.0996 (3) C25H29O4PS (M = 456.51), T = 213(2) K,
Monoclinic, P 21/n, a = 9.5308(11) b = 18.182(2) c = 14.0754(16) β =
◦
3
˚
93.703(2) V = 2434.1(5) A Z = 4, Reflections Collected = 15181, Inde-
pendent reflections = 5716 [R(int) = 0.0327], Final R indices [I > 2σ(I)]
R1 = 0.0582, wR2 = 0.1545 (4) C24H31BO4P, (M = 425.27), T = 213(2)
˚
˚
˚
K, triclinic, P-1, a = 9.5549(9) A, b = 10.7293(10) A, c = 12.7101(11) A,
◦
◦
◦
3
˚
α = 73.331(2) , β = 83.598(2) γ = 74.864(2) V = 1204.00(19) A Z = 2,
Reflections Collected = 10251, Independent reflections = 4322 [R(int) =
0.0229], Final R indices [I>2σ(I)] R1 = 0.0527, wR2 = 0.1462 (5)
C27H39BNO2P (M = 451.37), T = 213(2) K, Monoclinic, P 21/n, a =
◦
˚
˚
˚
15.737(2) A, b = 11.0004(16) A, c = 15.760(2) A, β = 111.509(2) , Z = 4,
Reflections Collected = 14562, Independent reflections = 4560 [R(int) =
0.0249], Final R indices [I > 2σ(I)] R1 = 0.0382, wR2 = 0.0970
Conclusions
In summary, we have characterized for the first time both a
phosphonothioic acid RP( S)(OH)2, and boranophosphonic acids
[RP(O)(BH−3 )(OH)]LH+ (where L is a Lewis base) by X-ray diffractom-
etry. The pKa measurements for 4 and 5 indicate that at physiological
pH, complete deprotonation would be achieved. All compounds were

Phosphonothioic and Boranophosphonic Acids
2227
synthesized in excellent yields from the same H-phosphinic acid pre-
cursor. Since structural parameters are important to the design of bioac-
tive compounds, and compounds of the type 2–5 have demonstrated or
potential value for this purpose, this work provides sets of comparable
structural data, and thus should be useful to future medicinally-related
applications.
Crystal data for compounds 1–5 is available free of charge from the
CCDC, reference numbers: 664468 – 664472.
REFERENCES
[1] (a) F. R. Hartley, Ed. The Chemistry of Organophosphorus Compounds, (Wiley, New
York, 1996), Volume 4; (b) P. Savignac and B. Iorga Modern Phosphonate Chemistry
(CRC Press, Boca Raton, 2003).
[2] K. Barral S. Priet J. Sire J. Neyts J. Balzarini B. Canardnd K. Alvarez J. Med. Chem.,
49, 7799 (2006).
[3] K. Swierczek A. S. Pandey J. W. Peters and A. C. Hengge, J. Med. Chem., 46, 3703
(2003).
[4] R. F. Barth A. H. Soloway R. G. Fairchild and R. M. Brugger, Cancer, 70, 2995 (1992).
[5] Search of Cambridge Crystallographic Database, 2007. Available online at: http://
www.codc.cam.ac.uk (accessed October 19 2007).
[6] H. H. Hatt, J. Chem. Soc, 776 (1933).
[7] (a) J.-L. Montchamp, Specialty Chemicals Magazine, 26, 44 (2006); (b) J.-L.
Montchamp, J. Organomet. Chem., 690, 2388 (2005); (c) K. Sasse, Ed. Methoden der
Organischen Chemie (Houben-Weyl) (Thieme, Stuttgart, 1964), Band XII/1, pp. 294–
337; (d) M. Regitz, Ed. Methoden der Organischen Chemie (Houben-Weyl) (Thieme,
Stuttgart, 1982), Vol. E2.
[8] S. Gouault-Bironneau, S. Depre`le. A. Sutor J.-L. Montchamp Org. Lett., 7, 5909
(2005).
[9] (a) V. Baskar M. Shanmugam E. C. San˜udo M. Shanmugam D. Collison E. J. L.
McInnes Q. Wei and R. E. P. Winpenny Chem. Commun., 37 (2007); (b) M. Shi Y.
Okamoto and S. Takamuku, Bull. Chem. Soc. Jpn., 63, 453 (1990).
[10] D. R. Boydnd G. Chignell, J. Chem. Soc., Trans., 123, 813 (1923).
[11] (a) A. Gautier, G. Garipova, C. Salcedo, S. Balieu, and S. R. Piettre, Angew. Chem.
Int. Ed., 43, 5963 (2004); (b) C. Selvam, C. Goudet, N. Oueslati, J.-P. Pin, and F. C.
Acher, J. Med. Chem., 50, 4656 (2007).
[12] K. Swierczek, J. W. Peters, and A. C. Hengge Tetrahedron, 59, 595 (2003).
[13] M. Mehring, M. Schu¨rmann, and R. Ludwig, Chem. Eur. J., 9, 838 (2003).
[14] M. J. Johansson A. Bergh and K. Larsson, Acta Cryst., C60, o312 (2004).
[15] J. S. Summers D. Roe P. D. Boyle M. Colvin and B. R. Shaw, Inorg. Chem., 37, 4158
(1998).
[16] T. Imamoto E. Nagato Y. Wada H. Masuda K. Yamaguchi and T. Uchimaru, J. Am.
Chem. Soc., 119, 9925 (1997).
[17] L. D. Quin, A Guide to Organophosphorus Chemistry (Wiley, New York, 2000).
[18] D. E. C. Corbridge, Phosphorus World: Chemistry, Biochemistry & Technology (2005).
[19] (a) P. Li, Z. A. Sergueeva, M. Dobrikov, and B. R. Shaw, Chem. Rev., 107, 4746
(2007; B. R. Shaw, M. Dobrikov, X. Wang, J. Wan, K. He, J.-L. Lin, P. Li, V. Rait, Z.
A. Sergueeva, and D. Sergueev, Ann. N. Y. Acad. Sci., 1002, 12 (2003).

2228
Y. Belabassi et al.
[20] (a) M. E. Druyan, A. H. Reis, Jr., E. Gebert, S. W. Peterson, G. W. Mason, and D.
F. Peppard, J. Am. Chem. Soc., 98, 4801 (1976); (b) A. H. Reis, Jr., S. W. Peterson,
M. E. Druyan, E. Gebert, G. W. Mason, and D. F. Peppard, Inorg. Chem., 15, 2748
(1976); (c) E. Urnezius and J. D. Protasiewicz, Main Group. Chem., 1, 369 (1996);
(d) B. Twamley, C.-S. Hwang, N. J. Hardman, and P. P. Power, J. Organomet. Chem.,
609, 152 (2000).
[21] (a) D. Fenske, R. Mattes, J. Lo¨ns, and K. F. Tebbe, Chem. Ber., 106, 1139 (1973); (b)
N. K. Skvortsov, S. V. Toldov, and V. K. Bel’skii, Russ. J. Gen. Chem., 64, 550 (1994);
(c) L. A. Aslanov, S. S. Sotman, V. B. Rybakov, L. G. Elepina, and E. E. Nifant’ev, Zh.
Strukt. Khim., 20, 758 (1979).
[22] (a) V. A. Uchtman and R. A. Gloss, J. Phys. Chem., 76, 1298 1972; (b) G. Ohms, K.
Kru¨ger, A. Rabis, and V. Kaiser Phosphorus, Sulfur, Silicon, Relat. Elem., 114, 75
(1996); (c) K. J. Langley, P. J. Squattrito, F. Adani, and E. Montoneri, Inorg. Chim.
Acta, 253, 77 (1996); (d) T. J. R. Weakley, Acta Crystallogr., B32, 2889 (1976); (e)
V. V. Tkachev, L. O. Atovmyan, B. V. Timikhin, O. A. Bragina, G. V. Ratovskii, and
¨
L. M. Sergienko, Zh. Strukt. Khim., 27, 121 (1986); (f) R. K. Chadha, G. Osapay,
Acta Crystallogr., C51, 2340 (1995); (g) D. DeLaMatter, J. J. McCullough, and C.
Calvo, J. Phys. Chem., 77, 1146 (1973); (h) S. W. Peterson, E. Gebert, A. H. Reis,
Jr., M. E. Druyan, G. W. Mason, and D. F. Peppard, J. Phys. Chem., 81, 466 (1977);
(i) E. Gebert, A. H. Reis, Jr., M. E. Druyan, S. W. Peterson, G. W. Mason, and D. F.
Peppard, J. Phys. Chem., 81, 471 (1977).
[23] H. Guo and M. Karplus J. Phys. Chem., 98, 7104 (1994).
[24] K. Merz and A. Knu¨fer Acta Crystallogr., C58, o187 (2002).
[25] G. M. Sheldrick, SHELXS-97, Program for the solution of crystal structures; Pro-
gram for the refinement of crystal structures (University of Go¨ttingen, Go¨ttingen,
Germany, 1997).