Synthesis and structure of stable water-soluble phosphonium alkanoate zwitterions derived from 1,3,5-triaza-7-phosphaadamantane

Article abstract of DOI:10.1007/s11224-015-0618-4

1,3,5-triaza-7-phosphaadamantane (PTA) was shown to form phosphonium alkanoate zwitterions with unsaturated dicarboxylic acids in water in the absence of strong acids. Solid-state structures of the phosphonium salt (1) derived from maleic or fumaric acids and that of the zwitterionic product (2) of the reaction of PTA with citraconic and mesaconic acids were determined by single-crystal X-ray diffraction. DFT calculations gave insight into the mechanism of the reaction, including the relative reactivity of the four dicarboxylic acids, and revealed the reasons for the lack of phosphonium salt formation by PTA in strongly acidic aqueous solutions.

Full text of DOI:10.1007/s11224-015-0618-4

Struct Chem
DOI 10.1007/s11224-015-0618-4
ORIGINAL RESEARCH
Synthesis and structure of stable water-soluble phosphonium
alkanoate zwitterions derived from 1,3,5-triaza-7-
phosphaadamantane
1
2
1,2
•
Antal Udvardy1,2 Mihaly Purgel Tımea Szarvas Ferenc Joo
•
•
•
´
´
´
2
´
Agnes Katho
´
Received: 16 June 2015 / Accepted: 19 June 2015
Ó Springer Science+Business Media New York 2015
Abstract 1,3,5-triaza-7-phosphaadamantane (PTA) was
shown to form phosphonium alkanoate zwitterions with
unsaturated dicarboxylic acids in water in the absence of
strong acids. Solid-state structures of the phosphonium salt
(1) derived from maleic or fumaric acids and that of the
zwitterionic product (2) of the reaction of PTA with
citraconic and mesaconic acids were determined by single-
crystal X-ray diffraction. DFT calculations gave insight
into the mechanism of the reaction, including the relative
reactivity of the four dicarboxylic acids, and revealed the
reasons for the lack of phosphonium salt formation by PTA
in strongly acidic aqueous solutions.
Introduction
Phosphonium salts play important role in chemistry,
especially as precursors of phosphorus ylides in synthesis
of olefins via the Wittig reaction [1, 2]. Oxidative coupling
of phosphonium salts is another method for obtaining
alkenes [3]. In most cases the required phosphonium salts
are obtained from triphenylphosphane by heating it with
the appropriate alkyl or benzyl halide in dry solvents [1, 2,
4], although one-pot Wittig reactions in water, with no
isolation of the intermediate phosphonium salt or the ylide,
have also been reported [5–7]. The reaction of PPh3
with lactones or a,b-unsaturated carboxylic acids is
facilitated by addition of trifluoroacetic acid [8]. The
mechanochemical reaction of PPh3 and solid alkyl halides
allowed solvent-free synthesis of phosphonium salts at
room temperature [9].
Keywords 1,3,5-triaza-7-phosphaadamantane Á
Phosphonium salt Á Maleic acid Á Fumaric acid Á
Zwitterion Á Water-soluble
Aqueous organometallic catalysis receives much atten-
tion as an environment-friendly way of organic synthesis,
and a large part of the catalysts contain various phosphane
ligands [10]. The most well known of the latter are the
monosulfonated and trisulfonated triphenylphosphanes,
generally used as Na salts (mtppms and mtppts, respec-
tively; Scheme 1). It has been observed that in aqueous–
organic biphasic systems, these tertiary phosphanes react
with alkyl halides, activated olefin as well as acetylene
carboxylic acids, or acrylonitrile yielding the correspond-
ing phosphonium salts [11].
This paper is dedicated to Professor Magdolna Hargittai in
recognition of her outstanding achievements in inorganic and
structural chemistry.
Electronic supplementary material The online version of this
article (doi:10.1007/s11224-015-0618-4) contains supplementary
material, which is available to authorized users.
& Antal Udvardy
udvardya@unideb.hu
In contrast to the reaction of PPh3 and a,b-unsaturated
acids which is reversible in anhydrous solvents and
needs addition of strong acids to drive the reaction to
completion, in aqueous solution, the carbanionic inter-
mediate produced by the reaction of sulfonated phos-
phanes and activated olefins is protonated by H2O, and
no acid additive is required [11]. Similarly, aldehydes
´
´
& Agnes Katho
katho.agnes@science.unideb.hu
1
MTA-DE Homogeneous Catalysis and Reaction Mechanisms
Research Group, P.O.B. 7, Debrecen 10 4010, Hungary
2
Department of Physical Chemistry, University of Debrecen,
P.O.B. 7, Debrecen 10 4010, Hungary
123

Struct Chem
P
SO3Na
reaction of both urotropine and PTA with alkyl halides
yield N-alkylated (azonia) products [21]. This is in contrast
to the easy P-alkylation of alkyl phosphanes. In agreement
with these findings, phosphonium salt formation was not
observed in the reaction of olefinic acids (maleic, fumaric)
[24, 25] and with aldehydes [12] under conditions where
sulfonated triphenylphosphanes showed smooth reactions
(room temperature, 0.1 M aq. HCl as solvent). On this
basis, PTA was suggested as an innocent ligand (in com-
parison to sulfonated tertiary phosphanes) of complexes
applied as catalysts in hydrogenation, hydroformylation
and other catalytic reactions of activated olefins in aqueous
media [24, 25].
P
NaO3S
SO3Na
P
N
N
N
SO3Na
mtppts-Na3
mtppms-Na
PTA
Scheme 1 Water-soluble tertiary phosphanes used in studies of
phosphonium salt formation with a,b-unsaturated acids in aqueous
solution
yielded 1-hydroxyalkyl-phosphonium salts with mtppms,
and one of the products was characterized by single-
crystal X-ray diffraction [12]. In contrast, reaction of the
water-soluble P[(CH2)3OH]3 and 3-phenylpropanal (di-
hydrocinnamaldehyde) in aqueous solution yielded the
corresponding 1-hydroxyalkyl-phosphonium salt only in
the presence of HCl [13]. The reaction of cinnamic acid
(PhCH=CH2COOH) with the water-soluble phosphanes
P[(CH2)3OH]3 or P(CH2OH)3 in acetone solution resulted
A few P-alkylated products (phosphonium salts) of
PTA, however, are known. They can be obtained by ring-
closure reaction of [RP(CH2OH)3]? [R=CH3(CH2)n, n =
0–3] with NH3 and HCHO, and the solid-state structure of
7-methyl-1,3,5-triaza-7-phosphaadamantane-7-ium
-
in formation of [HO(CH2)n]3P?CH(Ph)CH2CO2 (n = 1,
3) phosphabetaines [14, 15].
tetrafluoroborate ([P-methyl-PTA]BF4), obtained by this
method, has been determined [26]. Furthermore, in the
Morita–Baylis–Hillman a-hydroxyalkylation of ethyl
acrylate, catalyzed by PTA, the corresponding phospho-
nium salt, 7-(2-carboxyethyl)-1,3,5-triaza-7-phosphoni-
atricyclo[3.3.1.13,7]decane (P-(2-carboxyethyl)-PTA) was
isolated (Figure S1) [27], and its solid-state structure was
determined [28]. To remove the apparent contradiction in
the literature, we decided to reinvestigate the formation of
phosphonium salts in the reaction of PTA with olefindi-
carboxylic acids in water in the absence of strong acids.
Here we report the results obtained with maleic, fumaric,
citraconic, and mesaconic acids, and the structures of the
resulting phosphabetaines. DFT calculations have also
been made to reveal some mechanistic features of the
formation of these phosphonium alkanoate zwitterions.
Earlier we investigated the possible effect of phospho-
nium salt formation on the kinetics of hydrogenations
of various olefin carboxylic acids catalyzed by [RhCl
(mtppms-Na)3] in 0.1 M aqueous HCl as solvent [16]. For
comparison, mtppms was titrated with the substrate olefinic
acids at room temperature; both reactants were dissolved in
0.1 M aqueous HCl solution. Reaction of mtppms with
maleic acid, leading to the corresponding phosphonium salt
(phosphabetaine), was fast and complete at a 1:1 molar
ratio, while with fumaric acid 25 % of mtppms remained
unreacted under the same conditions. With crotonic acid,
the reaction proceeded only to a negligible extent.
The sulfonated triphenylphosphanes, mtppms and mtppts,
-
are water-soluble due to the presence of –SO3 groups. In
contrast to the expectations, 1,3,5-triaza-7-phosphaadaman-
tane (PTA; 1,3,5-triaza-7-phosphatricyclo[3.3.1.13,7]decane,
Scheme 1) dissolves in water as well, despite having no ionic
substituents. It is cheap, easy to synthesize, and in contrast to
most other phosphanes, it is stable to air oxidation even in
aqueous solution [17, 18]. For these reasons, it is often used as
ligand in water-soluble transition metal complexes for cat-
alytic purposes as well as for studies on possible medical uses
of Ru(II)-PTA complexes [19].
Experimental
General
1,3,5-triaza-7-phosphaadamantane (PTA) [22] and [N-
methyl-PTA]CF3SO3 [29] were prepared as described in
the literature. All other reagents were commercially
available and were used as received. Distilled and deoxy-
genated water was used throughout.
From coordination chemistry viewpoint, 1,3,5-triaza-7-
phosphaadamantane is a small, water-soluble, caged
alkylphosphane, often compared to trimethylphosphane
[20]. Conversely, it is the phosphorus analog of 1,3,5,7-
tetraaza-adamantane (urotropine); indeed, urotropine may
serve as starting material for the synthesis of PTA [21, 22].
Among other properties, similarity of PTA to urotropine is
shown also by the finding that dilute aqueous acids pro-
tonate one of the nitrogen atoms of both compounds [23],
while no P-protonated PTA is known. Furthermore,
Progress of the reactions was followed by 31P NMR
measurements, and the products were characterized also by
1H, 13C, and 31P NMR spectroscopies. NMR measurements
1
were run on a BRUKER DRX 360 spectrometer; H and
13C NMR spectra were referenced to tetramethylsilane
(TMS) or sodium 2,2-dimethyl-2-silapentane-5-sulfonate
123

Struct Chem
(DSS) standards, while for 31P NMR measurements 85 %
H3PO4 was used as reference.
13C{1H} NMR (90 MHz, D2O, 25 °C)d 175.78 (s,
3
COO-), 169.79 (s, COOH), 70.62 (d, JCP = 9 Hz,
1
Elemental analyses were obtained using an Elemen-
tarVario Micro (CHNS) equipment.
NCH2N), 48.76 (d, JPC = 36 Hz, P?CH2N), 40.15 (m,
P?CH), 30.22 (m, CHCHDCOO) ppm (Figure S6).
31P{1H} NMR (145 MHz, D2O, 25 °C)d -37.4 (s) ppm
(Figure S7).
Synthesis of phosphonium salts
(c) Reaction of PTA and maleic anhydride in aqueous
solution
Synthesis of 3-carboxy-2-(1,3,5-triaza-7-
phosphoniatricyclo[3.3.1.13,7]dec-7-yl)propanoate (1)
This reaction was carried out at 1 °C as in (a), but maleic
anhydride (98 mg, 1.0 mmol) was used instead of maleic
acid. Yield of 1: 189 mg (69 %).
(a) Reaction of PTA and maleic acid in aqueous solution
In a Schlenk tube, PTA (157 mg, 1.0 mmol) was dissolved
in 1.5 mL water and cooled to 1 °C. A solution of maleic
acid (117 mg, 1.0 mmol) in 1.0 mL water was added with
vigorous stirring in 5 min, and the colorless reaction
mixture was further stirred at 1 °C for 3 h. The solvent was
removed at reduced pressure, and the product was washed
with methanol (2 9 10 mL), with chloroform (2 9
10 mL), finally with diethyl ether (20 mL) and dried.
White powder; yield 203 mg (74 %).
(d) Reaction of PTA and fumaric acid in aqueous
solution
This reaction was carried out as in (a) but using fumaric
acid (117 mg, 1.0 mmol) instead of maleic acid. After 8-h
stirring at room temperature, 31P NMR showed 16.4 %
conversion of PTA into 1. The product was not isolated.
Synthesis of 3-carboxy-2-methyl-2-(1,3,5-triaza-7-
phosphoniatricyclo[3.3.1.13,7]dec-7-yl)propanoate (2)
The same reaction was carried out also at 50 °C. After
2-h stirring, the reaction mixture was worked up as above.
Yield of 1: 190 mg (70 %).
In a Schlenk tube, PTA (157 mg, 1 mmol) was dissolved in
2.5 mL water, and then citraconic acid (130 mg, 1 mmol)
was added and the mixture was heated for 48 h at 70 °C.
The solvent was removed at reduced pressure, and the oily
product was dissolved in 10 mL methanol. Crystals of the
pure product separated in three days, and these crystals
were filtered, washed with methanol (10 mL), chloroform
(3 9 10 mL), with diethyl ether (5 9 10 mL), and air-
dried. Yield of 2: 114 mg (40 %).
Anal. calcd. for C10H16PN3O4 (M = 273.20): C, 43.96;
H, 5.90; N, 15.38 %. Found: C, 43.87; H, 5.97; N,
15.33 %.
1H NMR (360 MHz, D2O, 25 °C) d 4.34–4.73 (m, 13H,
P?CH, P?CH2N and NCH2N) 2.58–3.26 (m, 2H,
CHCH2COOH) ppm (Figure S2).
13C{1H} NMR (90 MHz, D2O, 25 °C) d 175.73 (s,
3
COO-), 169.75 (s, COOH), 70.62 (d, JCP = 9 Hz,
1
NCH2N), 48.76 (d, JPC = 36 Hz, P?CH2N), 40.19 (m,
The same product was obtained after 9 months from the
reaction of PTA (500 mg, 3.18 mmol) and citraconic acid
(413.9 mg, 3.18 mmol) in a mixture of water (3 mL) and
acetone (3 mL) at room temperature (workup as above).
Yield of 2: 281 mg (24 %).
P?CH), 30.42 (s, CHCH2COO) ppm (Figure S3).
31P{1H} NMR (145 MHz, D2O, 25 °C) d -37.5 (s) ppm
(Figure S4).
(b) Reaction of PTA and maleic acid in D2O (synthesis
Anal. calcd for C11H18N3O4P 9 0.5 H2O (M =
296.23): C, 44.59; H, 6.46; N, 14.18. Found: C, 44.42; H,
7.14; N; 13.77 %.
of 1-D)
At 50 °C, 157 mg (1 mmol) PTA was dissolved in 1.5 mL
deoxygenated D2O. A solution of 117 mg (1 mmol) maleic
acid in 1 mL D2O was added dropwise to this solution with
strong stirring in 5 min, and the reaction mixture was
further stirred for 3 h at 50 °C. The solvent was removed at
reduced pressure, and the off-white solid was washed onto
a glass frit using 10 mL methanol where it was washed
further with methanol (10 mL) and chloroform
(2 9 10 mL) in order to remove PTA oxide. Finally, the
white product washed with diethyl ether (20 mL) and air-
dried. Yield of 1-D: 186 mg (68 %).
1H{P} NMR (360 MHz, D2O, 25 °C) d 4.32–4.62 (m,
12H, P?CH2N, NCH2N), 2.52–2.97 (m, 2H, CH2COOH),
1.40 (s, 3H, P?C–CH3) ppm.
1H NMR (360 MHz, D2O, 25 °C) d 4.32–4.62 (m, 12H,
P?CH2N, NCH2N), 2.52–2.97 (m, 2H, CH2COOH), 1.40
3
(d, JPH = 18 Hz, 3H, P?C–CH3) ppm (Figure S8).
13C{1H} NMR (90 MHz, D2O, 25 °C) d 174.86 and
3
174.30 (s, COO-, COOH), 70.48 (d, JCP = 9 Hz,
1
NCH2N), 48.95 (d, JCP = 36 Hz, P?C), 48.28 (d,
1JCP = 33 Hz, P?CH2N), 39.04 (s, CH2COOH), 18.84 (s,
1H NMR (360 MHz, D2O, 25 °C)d 4.29–4.73 (m, 13H,
P?CH, P?CH2N and NCH2N) 2.42–3.10 (m, 1H,
CHCHDCOOH) ppm (Figure S5).
CCH3) ppm (Figure S9).
31P{1H} NMR (145 MHz, D2O, 25 °C) d -35.4 (s) ppm
(Figure S10).
123

Struct Chem
Single-crystal X-ray diffraction measurements
carried out using Gaussian 09’s default integral equation
formalism variant (IEFPCM) PCM model [36, 37]. Tran-
sition state was optimized by means of the synchronous
transit-guided quasi-Newton method [38, 39]. The lack of
imaginary frequencies in vibrational spectral calculations
were taken to verify that the calculated stationary points on
the potential energy surfaces (PES) represented true min-
ima as opposed to transition states (TS). The relative
energies are Gibbs free energies obtained by frequency
analysis at 298 K. NBO analysis was also performed to
determine the donor–acceptor interactions inside the reac-
tants and the products.
X-ray quality crystals were obtained by layering 2-propa-
nol on concentrated aqueous solutions of 1 and 2.
Diffraction measurements were taken on a Bruker-Nonius
MACH3 four-circle diffractometer equipped with a point
detector using graphite-monochromated Mo-Ka radiation
˚
(k = 0.7107 A) with the x-scan method. Structures were
solved by the SIR-92 program [30] and refined by full-
matrix least-squares method on F2. Non-hydrogen atoms
were refined with anisotropic thermal parameters using the
SHELXL-97 package [31] (Table 1). Publication material
was prepared using the WINGX-97 suite [32] and the
Mercury program.
Results and discussion
DFT calculations
Synthesis and general characterization of 1 and 2
DFT calculations were performed with M06 [33] hybrid
functional and with the 6-311?G(d,p) triple-f Pople-type
basis sets with one set of diffuse and polarization functions
[34]. For the calculations, the Gaussian 09 software pack-
age has been used [35]. Geometry optimizations were
31P NMR spectroscopy revealed a spontaneous reaction of
PTA and olefindicarboxylic acids in aqueous solution. In
the 31P NMR spectrum of a solution containing equivalent
amounts of PTA and maleic acid, a new signal was
Table 1 Crystallographic data
and structure refinement results
for 1 and 2
1
2
Empirical formula
C10H16N3O4P
273.23
C11H20N3O4P 9 H2O
305.27
Formula weight
Crystal size (mm)
T (K)
0.32 9 0.21 9 0.20
293(2)
0.43 9 0.3 9 0.25
293(2)
˚
k (A)
0.71073
Orthorhombic
Pbca
0.71073
Monoclinic
P21/n
Crystal system
Space group
Color, shape
Prism/colorless
10.133(1)
12.823(4)
18.114(7)
90
Block/colorless
6.465(2)
11.700(3)
17.434(6)
90
˚
a (A)
˚
b (A)
˚
c (A)
a (°)
b (°)
c (°)
90
93.39(3)
90
90
3
˚
V (A )
2353.7(12)
8
1316.4(7)
4
Z
q calcd (g cm-3
l (mm-1
)
1.542
1.54
)
0.25
0.23
H range (°)
Total reflns.
Unique reflns.
2.8–25.3
2579
2.9–25.3
2654
2085
2654
Data/restraints/parameters
Final R indices [I [ 2r(I)]
R indices (all data)
GOF
2085/1/168
0.097
2654/4/192
0.088
0.195
0.239
0.98
1.02
-3
)
˚
Dqmax/Dqmin (eA
0.36/-0.37
0.62/-0.48
123

Struct Chem
detected at d = -37.5 ppm already after 30 min at 1 °C,
the intensity of which gradually increased in time accom-
panied with the intensity decrease in the signal at
d = -90.1 ppm characteristic for the starting material
(Fig. 1). In 3 h, this latter signal completely disappeared,
and only the 31P resonance of the new compound (together
with that of 3 % PTA oxide at d = -2.2 ppm) was
detected.
oxide). Increasing the temperature to 50 °C resulted in
formation of 56 % yield of 1; however, this was accom-
panied by extensive oxidation of PTA (26 % PTA oxide).
The reactions of 2-methylmaleic (citraconic) and
2-methylfumaric (mesaconic) acids with PTA were found
to be very slow. When a solution of citraconic acid was
added to an aqueous solution of PTA and left to react for
9 months, phosphonium salt 2 was formed with 44 %
conversion of PTA (Scheme 3). Under the same condi-
tions, mesaconic acid and PTA yielded 2 with 8.5 %
conversion (Scheme 3; determined by 31P NMR spec-
troscopy). At higher temperatures, the reactions are faster
(e.g., 40 % yield of 2 at 70 °C in 48 h; Scheme 3); how-
ever, significant amounts of PTA oxide are formed.
Similar to 1, the elemental analysis is in agreement with
the formulation of 2 as a zwitterion. Crystals of 2 suitable
for single-crystal X-ray diffraction measurements were also
isolated by layering 2-propanol on top of concentrated
aqueous solutions of 2. The solid-state structure of 2
together with that of 1 is discussed later.
For comparison, reactions of [N-methyl-PTA]? with
maleic and fumaric acids were also attempted. In an NMR
tube, 10 mg (0.032 mmol) [N-methyl-PTA]CF3SO3 reac-
ted with equivalent amounts of maleic and fumaric acids as
well as with maleic anhydride first at 1 °C for 4 h and then
at 50 °C for 4 h in 0.5 mL deoxygenated D2O. However,
formation of N-methylated phosphonium salts was not
observed in either case, and the 31P NMR spectra displayed
only a signal at d = -84.9 ppm characteristic for the [N-
methyl-PTA]? cation.
Similar observations were made when maleic acid was
replaced by maleic anhydride (Scheme 2). In case of
maleic acid, an increase in the reaction temperature to
50 °C resulted in formation of 64 % phosphonium salt and
4 % of phosphane oxide in 30 min, and the reaction was
complete in 2 h (95 % 1 and 5 % phosphane oxide). The
oxide could be removed by washing the crude products
with methanol and chloroform. In D2O as solvent, the
same procedure resulted in formation of the monodeuter-
ated phosphabetaine (1-D) with 68 % isolated yield
(Scheme 2).
In 1 and 1D, one of the carboxyl functions is protonated,
while the other is deprotonated and serves as counter ion to
the positively charged phosphorus. The suggested compo-
sition of 1 (Scheme 2) is in agreement with the data of
elemental analysis. Upon layering 2-propanol onto an
aqueous solution of 1, good-quality crystals were obtained,
and the solid-state structure of 1 was determined by single-
crystal X-ray diffraction. The structure (see later) agrees
well with formulation of 1 as a phosphabetaine.
Interaction of PTA with fumaric acid also yields 1;
however, the reaction is slow. Under the same conditions
as with maleic acid (T = 1 °C, t = 3 h), no reaction was
observed. In contrast, at room temperature, 8.8 % conver-
sion to 1 was detected after 1 day, and it increased to
16.4 % after 8 days (accompanied by 4.7 % of PTA
1 and 2 are stable to air oxidation. Their aqueous solu-
tions were kept at 80 °C for 6 h with no change in the 31P
NMR spectrum, and similarly, no oxidation took place
during the same reaction time in their solutions made with
aqueous 5 % H2O2. In 0.1 M NaOH solutions under air, no
sign of oxidation was detected; however, when 1 was
dissolved in 1.0 M aqueous NaOH, the phosphabetaine was
oxidized gradually with conversions of 18 % in 1 h, 46 %
in 4 h, and 100 % in 6 h.
Solid-state structures of 1 and 2
Solid-state structures of 1 and 2 were determined by single-
crystal X-ray diffraction; ORTEP diagrams are shown of
Fig. 2.
In both compounds, the carboxylic functions closer to
the positively charged phosphorus are deprotonated, while
the other remains protonated. In the known P-alkylated
PTA derivatives {(P-methyl)-PTA [26] and P-(2-car-
boxyethyl)-PTA [28]}, the C1–P, C2–P, and C3–P bond
distances are significantly shorter than in PTA [40]. The
same is observed in case of 1 and 2; in general, the C1–,
C2–, C3–P bond distances are closer to those in P-methyl-
Fig. 1 31P NMR spectra of the aqueous reaction mixtures containing
equivalent amounts of PTA and maleic acid as a function of time.
Conditions: PTA (157 mg, 1.0 mmol) and maleic acid (117 mg,
1.0 mmol) in 2.5 mL water, T = 1 °C
123

Struct Chem
O
Scheme 2 Formation of
phosphonium alkanoate
zwitterion 1 from PTA and
maleic or fumaric acids
O
O
HOOC
COOH or
-OOC
-OOC
COOH
COOH
D
H
T = 1 °C, t = 3 h, yield: 74 %
P
HOOC
COOH
P
P
N
N
D2O
H2O
N
N
N
N
N
COOH
HOOC
T = 50°C, t = 3 h, yield: 68 %
N
N
PTA
1-D
R.T., t = 8 day, conv.: 16.4%
1
O
OH
corresponding data of PTA, and this can be explained by
the rigidity of the adamantane-like cage structure of PTA.
However, in contrast to the equal and relatively small C1–
P–C2, C1–P–C3, and C2–P–C3 bond angles in PTA
(96.06°), the same angles in 1 and 2 are larger and fall into
the range of 100.0°–102.2°. In case of [P-methyl-PTA]BF4,
the same angles are in the 101.5°–103.2° range, i.e., the
PTA moieties within 1, 2 and [P-methyl-PTA]? are virtu-
ally identical. Conversely, the C1–P–C12 and C2–P–C12
angles are smaller, while the C3–P–C12 angle is larger in 1
and 2 than in [P-methyl-PTA]? with the consequence that
the P-C12 bonds in 1 and 2 do not coincide with the same
bond in [P-methyl-PTA]? (Figure S11).
O
HO
-OOC
COOH
conv.: 40 %
T=70°C, t=48h
P
H2O/acetone
P
N
N
N
r.t t= 9 month,
conv.: 8.5 %
N
N
N
PTA
O
2
HO
OH
O
Scheme 3 Formation of phosphonium alkanoate zwitterion 2 from
PTA and citraconic or mesaconic acids
PTA than to those in P-(2-carboxyethyl)-PTA (Table 2).
The C12–P distances in 1 and 2 are larger than in P-methyl-
PTA and close to that in P-(2-carboxyethyl)-PTA, and this
bond is longer in 1 than in 2; both observations are in
agreement with the reduced electron density on C12 due to
carboxylate substitution. The bond distance date refers to
P?–C(sp3) type bonds. The C=C bond distances in maleic
The crystals of 1 and 2 show layered structures built up
by layers of the apolar PTA moieties as well as by those of
the polar carboxylic acid residues.
An important finding is in that in the crystals of 1, there
is a strong hydrogen bond interaction between the C3
carbon and the O42 oxygen of the closer carboxylate group
˚
[dC3-H…O42 = 2.941(11) A]. In addition, strong hydrogen
bonds are formed between the protonated and deprotonated
˚
acid are 1.45 A [41]; for the phosphonium salts formed
with PTA, the C12–C13 distances were determined as
carboxylic/carboxylate groups [dO41-H…O12 = 2.480(10)
˚
A]. This leads to formation of molecular chains which are
˚
˚
1.499(10) A (1) and 1.508(12) A (2). This again shows the
presence of C(sp3)–C(sp3) single bonds in these
compounds.
packed into layers within the crystal. Weak H-bonding
interactions can be found between O11–C2, O11–C12, and
˚
Most of the bond distances and bond angle data of the
phosphonium salts 1 and 2 are close to those of the
O12–C3, too [dC2-H…O11 = 3.168 A, dC12-H…O11
=
˚
˚
3.194(12) A, and dC3-H…O12 = 3.104(11) A]. The H-bond
Fig. 2 ORTEP views of 1 and 2
at the 50 % probability level
with atom numbering. Selected
bond lengths and angles are
shown in Table 2
123

Struct Chem
Table 2 Selected bond
distances and bond angles in 1,
2, PTA [40], [P-methyl-
PTA]BF4 [26] and P-(2-
carboxyethyl)-PTA [28]
(1)
(2)
PTA
[P-methyl-PTA]-BF4a P-(2-carboxyethyl)-PTAa
˚
Bond distances (A)
C1–P
1.819(9)
1.810(9)
1.819(9)
1.826(8)
1.822(8)
1.789(8)
1.811(8)
1.818(9)
1.856(5) 1.812(3)
1.856(4) 1.811(3)
1.856(5) 1.808(3)
1.832(2)
1.831(2)
1.824(2)
1.807(2)
1.518(2)
N/A
C2–P
C3–P
Cl2–P
N/A
1.772(2)
N/A
C12–C13
C12–C15
Bond angles (°)
C1–P–C2
C1–P–C3
C2–P–C3
C1–P–C12
C2–P–C12
C3–P–C12
a
1.499(10) 1.508(12) N/A
N/A
1.532(12) N/A
N/A
101.6(4)
102.3(4)
100.4(4)
113.8(4)
112.6(4)
123.3(4)
100.0(4)
100.9(4)
102.2(4)
113.2(4)
115.1(4)
122.3(4)
96.06
96.06
96.06
N/A
101.5
101.8
103.2
115.9
115.0
117.3
99.6(9)
100.1(9)
102.4(9)
121.2(9)
105.9(9)
121.2(9)
N/A
N/A
For the numbering scheme of these compounds see Figure S1
Fig. 3 H-bond network and
layered structure of crystals of 1
network and the layered structure of the crystals of 1 are
shown in Fig. 3.
mentioned here that crystals of P-(2-carboxyethyl)-PTA
[25] also contain lattice water molecules, and these par-
ticipate in the hydrogen bond network by establishing an
Crystal structure of 2 is also influenced by the presence
of lattice water molecules. Similar to the case of 1, strong
hydrogen bonds are formed between the protonated and
˚
H-bond (d = 2.942 A) to one of the nitrogen atoms of the
PTA moiety. Such an interaction is obviously missing in
the crystal of 1 containing no lattice water. An even weaker
hydrogen bonding is observed between O12 and C3
deprotonated carboxylic/carboxylate groups [dO41-H…O12
=
˚
2.512(10) A]. There are strong hydrogen bonds also
between the O11 oxygen and the O1W lattice water oxygen
˚
[dC3-H…O11 = 3.001(11) A]; however, note that this dis-
˚
[dO1W-H…O11 = 2.798(10) A]. A somewhat weaker inter-
action is detected between the N3 nitrogen of PTA and
tance is shorter than the corresponding one in 1. The
H-bond network and the layered structure of the crystals of
2 are shown in Fig. 4.
˚
O1W [dO1W-H…N3 = 2.970(10) A]. For comparison, it is
123

Struct Chem
Fig. 4 H-bond network and the
layered structure of the crystals
of 2
Theoretical investigations
reactivity toward the acid monoanions (entries 1, 5, 9 or 2,
6, 10). Protonation of the carboxylate anion (i.e., reaction
with undissociated carboxylic acid) is similarly less
favorable (entries 1 vs 3; 5 vs 7; 9 vs 11), and the inter-
mediates are strongly destabilized in the reaction of
undissociated acids with protonated or N-methylated PTA
(PTAH and PTA-Me, respectively) as shown, for example,
by entries 7 and 11. The DG values of Table 2 are in
agreement with the experimentally observed higher reac-
tivity of maleic acid, in comparison with that of fumaric
acid. The dP–C distances increase with the increasing rel-
ative Gibbs free energies reflecting the weaker interactions
between the PTA phosphorus and the appropriate carbon
atoms of the unsaturated acids. Conversely, the increased
charge on PTA brought about by N-protonation or
N-methylation results in the decrease in the dP–O distances
(e.g., entries 1 vs 5 or 2 vs 6) due to the donor–acceptor
interaction of the anti-bonding orbital of the P–C1 bond
with the lone pair of one of the carboxylate oxygens. This
effect is largely eliminated by the protonation of the car-
boxylate oxygen (entries 5 vs 7 or 6 vs 8), and in the cases
of PTAH ? fumaric acid or PTAH ? maleic acid both the
dP–C and the dP–O, values are even larger than in the
PTA ? fumarate or PTA ? maleate systems (Table 4).
Reactions of half-deprotonated methylmaleic (citra-
conic) and methylfumaric (mesaconic) acids yield ener-
getically less favorable intermediates than maleate and
fumarate (entries 13, 14 vs 1, 2). The major reason for this
destabilization is that in the mesaconate and citraconate
monoanions, the carbon atom next to the methyl group
(i.e., one C atom of the C=C bond) is more positively
charged than in fumarate or maleate. In addition to this
unfavorable electronic effect, the steric requirement of the
methyl group should also be considered. However, in the
citraconate monoanion, the carboxylate group closer to the
methyl is perpendicular to the plane defined by the C=C
In order to get an insight into the formation as well as into
the structural and energetical properties of phosphonium
salts from PTA and unsaturated dicarboxylic acids, quan-
tum chemical (DFT) calculations were carried out. In
general the geometrical parameters, e.g., the C–P–C angles
of the PTA-based phosphonium salts are in good agreement
with the X-ray data (Figure S12 and Table S1.)
NBO calculations revealed significant donor–acceptor
interactions within the PTA molecule. Namely, the lone
electron pairs of the nitrogen atoms (N) are donated to the
unoccupied P–C and C–N bonds leading to increased sta-
bility of the molecule. It is known that on the action of
strong acids (such as HCl) PTA is protonated on one of its
nitrogen atoms [23]. According to the calculations, proto-
nation of PTA on N1 results in distortion in the electron
density distribution and the donor–acceptor interactions of
the protonated nitrogen disappear (Table 3).
The formation of phosphonium salts is a two-step pro-
cess. In the first step, one of the carbon atoms of the
ethylene unit of the unsaturated acid interacts with the PTA
molecule yielding a carbanionic intermediate. In the sec-
ond step, this intermediate is protonated on the other car-
bon atom of the ethylene unit. The calculated structures of
the intermediates formed from fumarate with PTA or
PTAH? are shown in Fig. 5.
The feasibility of phosphonium salt formation in reac-
tions of PTA, PTAH?, and N-methyl-PTA with several
unsaturated dicarboxylic acids or their monoanions was
assessed by calculation of relative Gibbs free energies of
the intermediates formed in the first step of the reactions.
The results, together with the relevant dP–C and dP–O dis-
tances, are shown in Table 4 (see also Fig. 5).
The data in Table 4 show unambiguously that both
protonation and methylation of PTA result in loss of
123

Struct Chem
Table 3 Selected donor–
acceptor interactions of PTA
and its derivatives
Molecule
Donor NBO
Acceptor NBO
DE (kcal/mol)
PTA
LP (N1)
LP (N1)
LP (N1)
LP (N2)
LP (N2)
LP (N2)
LP (N3)
LP (N3)
LP (N3)
LP (N2)
LP (N2)
LP (N2)
LP (N3)
LP (N3)
LP (N3)
LP (N2)
LP (N2)
LP (N2)
LP (N3)
LP (N3)
LP (N3)
LP (N1)
LP (N1)
LP (N1)
LP (N2)
LP (N2)
LP (N2)
LP (N3)
LP (N3)
LP (N3)
LP1 (O)
LP2 (O)
LP (N2)
LP (N2)
LP (N2)
LP (N3)
LP (N3)
LP (N3)
LP1 (O)
LP2 (O)
BD* (C4–N2)
BD* (C5–N3)
BD* (P–C1)
BD* (C4–N1)
BD* (C6–N3)
BD* (P–C2)
BD* (C5–N1)
BD* (C6–N2)
BD* (P–C3)
BD* (C4–N1)
BD* (C6–N3)
BD* (P–C5)
BD* (C5–N1)
BD* (C6–N2)
BD* (P–C3)
BD* (C4–N1)
BD* (C6–N3)
BD* (P–C2)
BD* (C5–N1)
BD* (C6–N2)
BD* (P–C3)
BD* (C4–N2)
BD* (C5–N3)
BD* (P–C1)
BD* (C4–N1)
BD* (C6–N3)
BD* (P–C2)
BD* (C5–N1)
BD* (C6–N2)
BD* (P–C3)
BD* (P–C1)
BD* (P–C1)
BD* (C4–N1)
BD* (C6–N3)
BD* (P–C2)
BD* (C5–N1)
BD* (C6–N2)
BD* (P–C3)
BD* (P–C1)
BD* (P–C1)
9.8
9.8
PTA
PTA
10.0
9.8
PTA
PTA
9.8
PTA
10.0
9.8
PTA
PTA
9.8
PTA
PTA(N1)H?
PTA(N1)H?
PTA(N1)H?
PTA(N1)H?
PTA(N1)H?
PTA(N1)H?
10.0
16.1
9.6
9.3
16.1
9.6
9.3
N1-methyl-PTA
N1-methyl-PTA
N1-methyl-PTA
N1-methyl-PTA
N1-methyl-PTA
N1-methyl-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
Fumarate-PTA(N1)H?
17.2
9.5
9.1
17.2
9.5
9.1
9.75
9.8
9.0
9.7
9.7
9.9
9.7
9.7
9.4
1.1
4.6
16.0
9.5
9.8
16.1
9.5
8.8
2.5
11.3
LP lone pair, BD* = unoccupied bond
bond (Fig. 6) which may result in stronger P–O interaction
facilitating the formation of the intermediate. In the case of
mesaconate, however, such an out-of-plane torsion of the
carboxylate group is not significant (Fig. 6); therefore, this
carboxylate is not able to act as an anchor during the for-
mation of the intermediate. This is in good agreement with
the relative energies of the intermediates of citraconate and
mesaconate (entries 13, 14).
These results of the calculations agree well with the
experimental findings in that citraconic acid reacts with
PTA much slower than maleic or fumaric acid (44 %
conversion in 9 months), while mesaconic acid shows
hardly any reactivity (8.5 % conversion in 9 months).
The second step of phosphonium salt formation is the
protonation of the intermediate carbanion. Synthesis of the
deuterated phosphobetaine, 1-D, using D2O as solvent
123

Struct Chem
Fig. 5 Structures of the
intermediates of the fumarate-
PTA (left) and the fumarate-
PTAH? reactions (right)
Table 4 Calculated relative
Gibbs free energies, dP–C and
dP–O distances of the
intermediates formed in the
PTA/PTAH—unsaturated
dicarboxylic acid/dicarboxylate
systems
Entry
Reactants
DG (kJ/mol)
dP–C (pm)
dP–O (pm)
1
PTA ? fumarate
75.8
71.6
184.4
184.3
184.8
185.3
188.4
187.0
189.2
186.3
188.3
186.8
190.6
189.2
186.4
196.5
265.4
262.9
288.4
283.3
239.8
231.4
275.4
279.1
239.8
231.3
273.5
270.7
260.8
259.2
2
PTA ? maleate
3
PTA ? fumaric acid
PTA ? maleic acid
PTAH ? fumarate
PTAH ? maleate
83.0
4
63.9
5
98.8
6
101.9
124.6
124.5
102.5
94.4
7
PTAH ? fumaric acid
PTAH ? maleic acid
PTA-Me ? fumarate
PTA-Me ? maleate
PTA-Me ? fumaric acid
PTA-Me ? maleic acid
PTA ? mesaconate
PTA ? citraconate
8
9
10
11
12
13
14
130.7
107.2
90.2
83.8
process are presented in the Supporting Information
(Table S2). It can be seen that coordination sphere around
phosphorus is more symmetric in the products due to the
disappearance of the large conjugated electron system upon
protonation of the intermediates.
Fig. 6 Structures of the citraconate (left) and mesaconate (right)
monoanions
Conclusion
Although in anhydrous solvents the reaction of PPh3 with a,b-
unsaturated carboxylic acids is facilitated by addition of tri-
fluoroacetic acid, and sulfonated triphenylphosphanes
(mtppms, mtppts) also react readily with activated olefins in
strongly acidic aqueous solutions, under the same conditions no
formation of phosphonium salts was observed when mtppms or
mtppts was replaced by 1,3,5-triaza-7-phosphaadamantane
(PTA). In contrast to these earlier observations PTA was shown
to form phosphonium salts (phosphonium alkanoate zwitteri-
ons) with unsaturated dicarboxylic acids in aqueous solutions
provides evidence for the solvent acting as deuterium (or
proton) source. Protonation may happen from the solvent
molecules either directly or by a carboxylate-assisted proton
transfer. The activation barriers of this step were found in the
wide range of 30–100 kJ/mol, largely depending on the
orientation of the solvent molecules yielding products in a
strongly exergonic pathway. As an example, a water-assisted
proton transfer from the carboxylic unit to the C=C bond has
the following calculated parameters: DG= = ?31.2 kJ/mol
and DGr = -112.9 kJ/mol. The transition states of this
123

Struct Chem
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in the absence of strong acid additives. Although the reactions
were slow, high yield of the corresponding phosphonium salt
(1) could be obtained in reaction of PTA with maleic acid or
fumaric acid. Methylmaleic (citraconic) and methylfumaric
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Acknowledgments This research was supported by the European
Union and the State of Hungary, co-financed by the European Social
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ments. The participation of Henrietta Molnar in the initial experiments
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is gratefully acknowledged. The research was supported by the EU and
co-financed by the European Social Fund under the project ENVIKUT
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