A simple procedure to ditertiary phosphinocarboxylic acids and their bisphosphine oxides

Article abstract of DOI:10.1080/10426507.2012.743133

A simple two-step route to a series of carboxylic acid functionalized ditertiary phosphine oxides is described, including the X-ray crystal structures of three representative examples namely {Ph₂P(O)CH₂} ₂N(CH₂)nCO₂H (n = 3-5). Strong intermolecular O-H···O H-bonding is observed in all cases leading to distinct packing arrangements.

Full text of DOI:10.1080/10426507.2012.743133

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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A Simple Procedure to Ditertiary
Phosphinocarboxylic Acids and Their
Bisphosphine Oxides
Mark R. J. Elsegood a , Thomas A. Noble a , Salem Talib a & Martin B.
Smith a
a Department of Chemistry, Loughborough University ,
Loughborough , Leicestershire , LE11 3TU , UK
Published online: 08 May 2013.
To cite this article: Mark R. J. Elsegood , Thomas A. Noble , Salem Talib & Martin B. Smith (2013) A
Simple Procedure to Ditertiary Phosphinocarboxylic Acids and Their Bisphosphine Oxides, Phosphorus,
Sulfur, and Silicon and the Related Elements, 188:1-3, 121-127, DOI: 10.1080/10426507.2012.743133
To link to this article: http://dx.doi.org/10.1080/10426507.2012.743133
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Phosphorus, Sulfur, and Silicon, 188:121–127, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2012.743133
A SIMPLE PROCEDURE TO DITERTIARY
PHOSPHINOCARBOXYLIC ACIDS AND THEIR
BISPHOSPHINE OXIDES
Mark R. J. Elsegood, Thomas A. Noble, Salem Talib,
and Martin B. Smith
Department of Chemistry, Loughborough University, Loughborough,
Leicestershire LE11 3TU, UK
GRAPHICAL ABSTRACT
Abstract A simple two-step route to a series of carboxylic acid functionalized ditertiary
phosphine oxides is described, including the X-ray crystal structures of three representative
examples namely {Ph2P(O)CH2}2N(CH2)nCO2H (n = 3−5). Strong intermolecular O−H···O
H-bonding is observed in all cases leading to distinct packing arrangements.
Keywords Tertiary phosphine oxides; ligands; hydrogen bonding; NMR spectroscopy; X-ray
crystallography
INTRODUCTION
Phosphine oxides are versatile compounds for diverse applications in organic syn-
thesis,1–3 photoinitiators for surface modification,4 preparation of quantum dots,5 coor-
dination chemistry,6 and industrial processes such as selective metal extraction.7 Some
Received 4 September 2012; accepted 18 October 2012.
We would like to thank Loughborough University and The Leverhulme Trust (S.T.) for funding.
Address correspondence to Dr. Martin B. Smith, Department of Chemistry, Loughborough University
Loughborough, Leicestershire LE11 3TU, UK. E-mail: m.b.smith@lboro.ac.uk
121

122
M. R. J. ELSEGOOD ET AL.
Figure 1 Some examples of phosphine oxides.
representative examples of phosphine oxides used in these scenarios are illustrated in
Figure 1. Bis(phosphine) oxides are known2,8 and often incorporate a carbon connectiv-
ity between both –P(O)R2 groups (where R = Ph typically). Carboxylic acid bearing
ditertiary phosphines and their oxides are attractive targets, yet their ease of prepara-
tion and suitability to our program were inappropriate.2, 8 Phosphorus based Mannich
transformations are an extremely useful synthetic method for accessing new “hybrid” lig-
ands.9, 10 Keglevich and coworkers9 recently showed bis(phosphine) oxides of the type
{Ph2P(O)CH2}2N(R) are accessible via the microwave assisted double phospha-Mannich
reaction of HP(O)Ph2, (CH2O)n and various arylamines. Our research group10 is also in-
terested in P−C−N(R)−C−P based ligands and we required access to readily amenable
ditertiary phosphine bisoxides, bearing N-backbone functionality for further modification.
Herein we describe a simple, high yielding, two-step method for the synthesis of new
carboxylic acid modified ditertiary phosphine bisoxides derived from cheap, commercially
available, starting materials. The structures of {Ph2P(O)CH2}2N(CH2)nCO2H (n = 3 2c; n
= 4 2d, and n = 5 2e) have been determined by single crystal X-ray diffraction and reveal
different structural H-bonding motifs as a function of alkyl spacer chain length.
RESULTS AND DISCUSSION
Using a procedure similar to that recently developed by us10 for preparing novel
carboxylic acid functionalized ditertiary phosphines, reaction of two equivalents of
Ph2PCH2OH (readily preformed from equimolar amounts of [CH2O]n and Ph2PH)11 with
one equivalent of H2N(CH2)nCO2H (n = 1−5, 11) in refluxing CH3OH, gave the condensed
ligands {Ph2PCH2}2N(CH2)nCO2H 1a–f (Scheme 1). Compounds 1a–f were characterized
1
in situ by 31P{ H} NMR spectroscopy (Table 1). As demonstrated by the facile synthesis of
1a–f, this simple method unsurprisingly appears insensitive to alkyl chain length with no
1
significant amounts of other phosphorus species observed by 31P{ H} NMR spectroscopy.
Oxidation of 1a–f, under standard conditions (aq. H2O2/THF/r.t.)12 and subsequent work-
up, gave the corresponding ditertiary phosphine bisoxides 2a–f (Scheme 1) as colorless
1
solids. The unoptimized yields for 2a–f are in the range 60–77% (Table 1). The 31P{ H}
NMR data (Table 1) confirm oxidation of both phosphorus centers since only one singlet
31P resonance is observed at ca. δ(P) 30 ppm. Our data is in good agreement with those
of known phosphine oxides9 and, moreover, these 31P NMR resonances are some 50 ppm
downfield with respect to the trivalent precursors 1a–f. All compounds were further charac-
terized by 1H NMR, FT−IR and elemental analysis (see Experimental Section for selected
data). Compounds 2a–f are freely soluble in CH2Cl2, THF, and CH3OH, but show limited
solubility in CH3CN and H2O (the lower alkyl chain members are soluble in basic media).

BISPHOSPHINE OXIDES
123
Scheme 1 (i) 2 Ph2PCH2OH, CH3OH, reflux (ii) aq. H2O2, THF.
Suitable crystals of 2c, 2d, and 2e were obtained by vapor diffusion of diethyl
ether into a CDCl3 solution over the course of several days. The single crystal X-ray
structures13 of 2c (Figure 2), 2d, and 2e have been determined with selected bond lengths
and angles given in Table 2. In all cases, the X-ray structures confirm the presence of
both –P(O)Ph2 and –CO2H groups. The –P(O)Ph2 groups adopt an anti configuration
with respect to each other and the P O bond lengths [1.486(2)–1.499(3) Å] are in the
normal range.9 Furthermore, in all three structures, the central nitrogen atom is clearly
ꢀ
pyramidal as indicated by the [N(1) angles] of 337◦ (2c), 341◦ (2d), and 339◦ (2e).
The most unusual feature between all three X-ray structures, none of which incorporate
solvent cocrystallization, are the different packing arrangements on going from 2c (C3) to
2d (C4) to 2e (C5) (Figures 3a–c). In 2c, molecules are linked into a 1-D zig-zag chain
through strong O H···O intermolecular H-bonding [O(4)···O(2ꢁ) 2.621(4) Å, H(4)···O(2ꢁ)
1
Table 1 Selected experimental and 31P{ H} NMR data for 1a–f and 2a–f
Compound
Reaction time (h)
Yield (%)a
δ(P) (ppm)c
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
19
5b
−26.4
−27.8
−27.6
−27.8
−27.9
−27.7
29.5
30.0
30.0
30.6
30.2
21
19
20
16
1.5
1.5
1.5
1.5
4
77
70
61
62
60
60
4
30.1
a Yields for 1a−f not determined.
b Reaction conducted at r.t.
1
c 31P{ H)} NMR spectra were recorded (101.23, 161.97, or 202.46 MHz) in CH3OH/C6D6 (for 1a−f) and
CDCl3 (2a−f).

124
M. R. J. ELSEGOOD ET AL.
Figure 2 Crystal structure of 2c. Compounds 2d and 2e are ostensibly similar and not shown. All hydrogen
atoms except H(4) have been omitted for clarity.
1.68(2) Å; O(4)−H(4)···O(2ꢁ) 166(4)◦], whereas in 2d, strong O−H···O intermolecular
H-bonding O(4)···O(2ꢁ) 2.589(3) Å, H(4)···O(2ꢁ) 1.73(3) Å; O(4)−H(4)···O(2ꢁ) 164(3)◦]
leads to spirals (21 screw axis) that run along the crystallographic a axis.14 In 2e, molecules
form discrete dimer pair through P O···H−O hydrogen bonding [O(4)···O(1ꢁ) 2.585(2)
Å, H(4)···O(1ꢁ) 1.73(3) Å; O(4)−H(4)···O(1ꢁ) 167(3)◦]. This leads to formation of a large
24-membered ring as opposed to the more classical carboxylic acid-carboxylic acid head-
to-tail 8-membered ring through pairs of C O···H−O hydrogen bonds.10, 15 Furthermore,
additional weak intermolecular C−H···O contacts were observed in 2c–e. All attempts to
obtain suitable crystals of 2a, 2b, or 2f were unsuccessful.
Table 2 Selected bond lengths (Å) and angles (◦) for 2c–e
2c
2d
2e
P(1)−O(1)
P(2)−O(2)
1.489(3)
1.499(3)
1.202(5)
1.325(4)
112.0(3)
1.486(2)
1.4911(18)
1.213(3)
1.323(3)
111.2(2)
1.4962(15)
1.4902(16)
1.209(3)
1.325(2)
111.24(15)
C
C
O(3)
O(4)
C(1)−N(1)−C(2)

BISPHOSPHINE OXIDES
125
Figure 3 Packing diagrams of (a) 2c, (b) 2d, and (c) 2e. All hydrogen atoms except those on CO2H groups
have been omitted for clarity.
In summary, we have shown, new carboxylic acid modified ditertiary phosphine
bisoxides are readily accessible. This procedure should be tolerant to other reactive func-
tional groups, and current efforts are directed toward tagging these precursors onto biocon-
jugate and polymeric supports. Related hydroxyalkyl aminophosphonic acids have recently
been used to prepare novel composite films.16

126
M. R. J. ELSEGOOD ET AL.
EXPERIMENTAL
The following method was used for the synthesis of 2a. To the solids Ph2PCH2OH
(0.513 g, 2.37 mmol) and H2NCH2CO2H (0.085 g, 1.13 mmol) was added oxygen-free
CH3OH (20 mL). The solution was refluxed for 19 h under a N2 atmosphere. The solvent
was evaporated to dryness under reduced pressure to afford 1a. THF (15 mL) was added
followed by H2O2 (1.5 mL, 27.5 wt% solution in water) and the solution stirred at r.t. for
1.5 h. The solvent was evaporated to dryness, the residue taken up in CH2Cl2 (30 mL)
and washed with H2O (30 mL). The organic layer was dried over anhydrous MgSO4, the
solvent reduced to ca. 5 mL and Et2O (30 mL) added. Yield: 0.46 g, 77%. Selected data for
2a: 1H NMR [CDCl3, 298 K]: δ = 7.76−7.34 (m, 20H, arom-H), 3.76 (d, 2JPH = 4.9 Hz,
4H, PCH2), 2.97 (t, 2H, CH2). FT−IR (KBr): 1715 cm−1 (νCO). Calcd. for C28H27NO4P2:
1
C, 66.80; H, 5.42; N, 2.78. Found: C, 66.46; H, 5.75; N, 2.40. Selected data for 2b: H
NMR [CDCl3, 298 K]: δ = 7.73−7.36 (m, 20H, arom-H), 3.79 (s, 4H, PCH2), 3.23 (s, 2H,
CH2), 2.53 (s, 2H, CH2). FT−IR (KBr): 1717 cm−1 (νCO). Calcd. for C29H29NO4P2: C,
67.30; H, 5.66; N, 2.71. Found: C, 66.92; H, 5.60; N, 2.74. Selected data for 2c: 1H NMR
2
[CDCl3, 298 K]: δ = 7.86−7.32 (m, 20H, arom-H), 3.76 (d, JPH = 3.6 Hz, 4H, PCH2),
2.97 (t, 2H, CH2), 2.15 (t, 2H, CH2), 1.69 (m, 2H, CH2). FT−IR (KBr): 1715 cm−1 (νCO).
Calcd. for C30H31NO4P2: C, 67.78; H, 5.89; N, 2.64. Found: C, 67.12; H, 5.84; N, 2.67.
1
Selected data for 2d: H NMR [CDCl3, 298 K]: δ = 7.74−7.25 (m, 20H, arom-H), 3.66
2
(d, JPH = 4.0 Hz, 4H, PCH2), 2.89 (t, 2H, CH2), 2.21 (t, 2H, CH2), 1.39 (m, 2H, CH2),
1.31 (m, 2H, CH2). FT−IR (KBr): 1716 cm−1 (νCO). Calcd. for C31H33NO4P2: C, 68.24;
H, 6.11; N, 2.57. Found: C, 67.83; H, 5.93; N, 2.59. Selected data for 2e: 1H NMR [CDCl3,
298 K]: δ = 7.87−7.32 (m, 20H, arom-H), 3.75 (d, 2JPH = 4.4 Hz, 4H, PCH2), 2.97 (t, 2H,
CH2), 2.22 (t, 2H, CH2), 1.52 (m, 2H, CH2), 1.34 (m, 2H, CH2), 1.08 (m, 2H, CH2). FT−IR
(KBr): 1700 cm−1 (νCO). Calcd. for C32H35NO4P2: C, 68.68; H, 6.32; N, 2.50. Found: C,
67.68; H, 6.15; N, 2.60. Selected data for 2f: 1H NMR [CDCl3, 298 K]: δ = 7.80−7.37 (m,
20H, arom-H), 3.76 (d, 2JPH = 4.4 Hz, 4H, PCH2), 2.97 (t, 2H, CH2), 2.36 (t, 2H, CH2),
1.69−1.06 (m, 18H, CH2). FT−IR (KBr): 1718 cm−1 (νCO). Calcd. for C38H47NO4P2: C,
70.89; H, 7.37; N, 2.18. Found: C, 70.93; H, 7.37; N, 2.32.
Crystal data for 2c: C30H31NO4P2, M = 531.50; monoclinic, P21/n, a = 7.7628(7), b
= 35.747(3), c = 10.2069(9) Å, β = 108.2102(17)◦, V = 2690.5(4) Å3; Z = 4, ρcal 1.312 g
cm−3; μ(Mo-Kα) = 0.198 mm−1; λ = 0.71073 Å, T = 150(2) K; 19529 reflections were
collected on a Bruker SMART 1000 CCD diffractometer13 using narrow ω-scans, 4743 of
which were independent (Rint = 0.0785). The structure was solved by direct methods and
refined on F2 values to give a final R1 = 0.0577 for 2837 data with F2>2σ (F2); wR2 =
0.1497 for all data.17, 18 Crystal data for 2d: C31H33NO4P2, M = 545.52; orthorhombic,
P212121, a = 7.9895(5), b = 16.9972(10), c = 20.1654(12) Å, V = 2738.4(3) Å3; Z = 4, ρcal
1.323 g cm−3; μ(Mo-Kα) = 0.197 mm−1; λ = 0.71073 Å, T = 150(2) K; 24123 reflections
were collected on a Bruker SMART 1000 CCD diffractometer using narrow ω-scans, 6677
of which were independent (Rint = 0.0532). The structure was solved by direct methods
and refined on F2 values to give a final R1 = 0.0507 for 4723 data with F2 > 2σ (F2); wR2
= 0.1044 for all data. Flack x = 0.01(10). Crystal data for 2e: C32H35NO4P2, M = 559.55;
monoclinic, P21/n, a = 7.9659(5), b = 17.8259(11), c = 20.7005(13) Å, β = 96.0029(11)◦,
V = 2923.3(3) Å3; Z = 4, ρcal 1.271 g cm−3; μ(Mo-Kα) = 0.186 mm−1; λ = 0.71073 Å, T =
150(2) K; 25371 reflections were collected on a Bruker SMART 1000 CCD diffractometer
using narrow ω-scans, 6995 of which were independent (Rint = 0.0398). The structure was
solved by direct methods and refined on F2 values to give a final R1 = 0.0448 for 4762

BISPHOSPHINE OXIDES
127
data with F2>2σ (F2); wR2 = 0.1181 for all data. A complete set of X-ray crystallographic
structural data for compounds 2c–e (CCDC numbers 897295, 897296, and 214336) are
available at the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge,
CB2 1EZ, UK (fax: +44 1223 336 033; e-mail: deposit@ccdc.ac.uk) on request, quoting
the deposition number.
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