A reinvestigation of mono-and bis-ethynyl phosphonium salts: Structural and computational studies and new reactivity

Article abstract of DOI:10.1139/cjc-2017-0482

A series of mono-and bis-ethynyl phosphonium salts have been prepared via reaction of bromoacetylenes, Ph-C≡C-Br or Br-C≡C-C₆H₄-C≡C-Br, with various phosphines. Some of the derivatives reported are previously known, ([Ph-C≡C-PPh₃]Br, [Ph-C≡C-PMe₃]Br, [Ph-C≡C-PBu₃]Br, and [Ph₃P-C≡C-C₆H₄-C≡C-PPh₃][Br₂]), however typically these are missing complete spectroscopic characterization and many have been prepared using much more complicated methods. The derivative [Ph-C≡C-PPh₃]Br is capable of inhibiting the growth of tumour cells and has been shown crystallographically to have a significant interaction with the heat shock proteins (HSP70 or DnaK). Thus, solid state structures for all seven phosphonium salts prepared have been reported as they may be of interest to others in this field. Sterically encumbered phosphines such as Mes₃P did not react with Ph-C≡C-Br; however, (2,4,6-MeO-C₆H₂)₃P was found to slowly react at moderate temperature to give the expected alkynyl phosphonium salt. However, at higher temperatures, the alkynyl phosphonium undergoes an intramolecular cyclization to form a phosphonium analogue of a 1,4-oxazine. Finally, electronic structure calculations reveal the positive charge on the acetylenic β-carbon, a result of a significant contribution of other canonical structures. The flexibility of the P-C≡C bond has been investigated showing a low-energy barrier (<5 kcal/mol) for bending up to 40° from the optimized angle in the model [Ph-C≡C-PMe₃]⁺ cation. This ease of bending may be of significance in the development of other alkynyl phosphonium tumour cell growth inhibitors.

Full text of DOI:10.1139/cjc-2017-0482

Page 1 of 43
A reinvestigation of mono- and bis-ethynyl phosphonium salts: structural and
computational studies and new reactivity
Alex J. Veinot, Angela D. K. Todd, Katherine N. Robertson, and Jason D. Masuda*
The Atlantic Centre for Green Chemistry and the Department of Chemistry, Saint Mary’s
University, 923 Robie St., Halifax, Nova Scotia, Canada, B3H 3C3. Email: Jason.Masuda@smu.ca.

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ABSTRACT:
A series of mono- and bis-ethynyl phosphonium salts have been prepared via reaction of
bromoacetylenes, Ph-C≡C-Br or Br-C≡C-C6H4-C≡C-Br, with various phosphines. Some of the
derivatives reported are previously known, ([Ph-C≡C-PPh3]Br, [Ph-C≡C-PMe3]Br, [Ph-C≡C-
PBu3]Br, and [Ph3P-C≡C-C6H4-C≡C-PPh3][Br2]), however typically these are missing complete
spectroscopic characterization and many have been prepared using much more complicated
methods. The derivative, [Ph-C≡C-PPh3]Br is capable of inhibiting the growth of tumour cells
and has been shown crystallographically to have a significant interaction with the heat shock
proteins (HSP70 or DnaK). Thus, solid state structures for all seven phosphonium salts prepared
have been reported as they may be of interest to others in this field. Sterically encumbered
phosphines such as Mes3P did not react with Ph-C≡C-Br, however (2,4,6-MeO-C6H2)3P was
found to slowly react at moderate temperature to give the expected alkynyl phosphonium salt.
However at higher temperatures, the alkynyl phosphonium undergoes an intramolecular
cyclization to form a phosphonium analogue of a 1,4-oxazine. Finally, electronic structure
calculations reveal the positive charge on the acetylenic β-carbon; a result of a significant
contribution of other canonical structures. The flexibility of the P-C≡C bond has been
investigated showing a low-energy barrier (<5kcal/mol) for bending up to 40° from the
optimized angle in the model [Ph-C≡C-PMe3]+ cation. This ease of bending may be of
significance in the development of other alkynyl phosphonium tumour cell growth inhibitors.
Keywords: main group chemistry, phosphorus, phosphonium, X-ray crystallography
Introduction

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Since their initial discovery1, ethynylphosphonium salts continue to be popular and
extremely valuable building blocks in organic synthesis. These compounds have
classically been used as electrophiles allowing for the isolation of numerous
vinylphosphonium containing adducts2-9, but have also been used as intermediates in
the synthesis of functionalised coumarins10, and as monomer units in the formation of
ionic porous organic polymers.11 More recent interests lie in the potential for
(phenylethynyl)phosphonium salts to be used as therapeutic agents for cancer
treatment.12-14 Ethynyl-phosphonium salts of the type [R3PC≡CR”]X (R/R” = alkyl and/or
aryl) are uncommon in the literature and are most commonly synthesized via
quaternization of tertiary phosphines with alkynyl halides.2,3,15-18 Other routes are
known19,20, but have not seen extensive use. Modification of ethynylphosphonium salts
typically takes place at the acetylene R” position19,21, while structural diversity within the
ligands bound to phosphorus remains to be an underdeveloped area.
After examining the literature, it was found that despite their widespread use there is
relatively little structural data available for the simplest of ethynylphosphonium salts
(Scheme 1), and early spectroscopic data was determined to be incomplete (
).3,18,22
1
)3, or
two
scattered
throughout
the
literature
(
2
To
date,
only
phenyl(ethynylphosphonium) salts have been structurally characterised using X-ray
crystallography (317 and 46). Structural properties related to these compounds are
significant because it has been recently discovered that
2 is capable of inhibiting the
mammalian protein HSP70 its bacterial analogue DnaK by binding to C-terminal

Page 4 of 43
allosteric pockets via its phenylacetylene fragment.12 These proteins are important for
mediating a wide variety of cellular functions, particularly during periods of increased
cellular stress, and are essential for the survival of tumour cells. Recent studies have
demonstrated that the inhibition of these proteins with compound
2 is a promising
strategy for the treatment of cancers that heavily rely on heat shock proteins such as
multiple myeloma.12-14 Evidence that the phenylacetylene fragment of
2
interacts
significantly with DnaK was provided by protein crystallography with a resolution limit
3.45 Å.12 Although suitable for protein crystallography, at this resolution limit it becomes
impossible to elucidate any fine structural details of the inhibitor that could allow for the
fine-tuning of structural features. Some closely related compounds involving the
acetylenic fragment either σ- or π-bound to a metal23-25, or cationic phosphorus
heterocycles are known26-28, but these examples are too specific to provide
representative structural details that may be relevant for further studies on protein
binding.
The closely related bis(ethynylphosphonium) salts are much less common in the literature;
to the best of our knowledge, all known bis(ethynylphosphonium) salts separated by an organic
linker are shown in Scheme 2. Beyond demonstrating their syntheses these compounds have
received very little attention despite being likely to exhibit chemistry similar to their related
mono-substituted analogues. Their initially published synthesis required the
carbodiphosphorane Ph3P=C=PPh3, limiting the scope of these compounds to just phenyl
substituents attached to phosphorus.19 A more recent synthesis has also been reported20, but is

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also undesirable because it requires multiple steps to complete and produces multiple
equivalents of toxic (n-Bu)3SnCN as waste.
Considering recent developments in the medicinal properties of these compounds
and their relevance in organic synthesis, we found it prudent to reinvestigate several of
these mono(ethynylphosphonium) salts to determine their structural features and to
consolidate the characterization data in the literature. Additionally, a simplified, greener
approach to the synthesis for bis(ethynylphosphonium) salts is reported to expand the
applications of these compounds that are potentially useful for organic synthesis.
Experimental
General Synthetic Procedures
All reactions were performed in dry, O2-free conditions under an atmosphere of N2
within an mBraun Labmaster SP inert atmosphere drybox or PTFE-sealed reaction vessels using
standard Schlenk techniques. Ph-C≡C-Br and Br-C≡C-C6H4-C≡C-Br were prepared following
literature procedures.29 All reagents were purchased from Sigma-Aldrich and used as received,
unless otherwise noted. Alumina and molecular sieves were pre-dried in a 150°C oven before
bring dried at 300°C in vacuo. Solvents were purified using an Innovative Technology solvent
purification system or purchased as ‘anhydrous’ from Sigma-Aldrich. Solvents were then dried
using KH and subsequently filtered through dry alumina and stored over previously dried 4Å
molecular sieves. Glassware was dried at 150°C overnight prior to experimentation. NMR

Page 6 of 43
spectra were recorded on a Bruker Avance 300MHz spectrometer. Trace amounts of non-
1
deuterated solvent were used as internal references for H NMR spectra and were referenced
relative to tetramethylsilane. The deuterated solvent was used as an internal reference for
13C{1H} NMR spectra and referenced relative to tetramethylsilane. Phosphoric acid was used as
an external standard for 31P NMR. Coupling constants are reported as absolute values. Melting
points were recorded on an Electrothermal MEL-Temp 3.0 using glass capillaries sealed under
inert conditions. Elemental analysis was performed by the Centre for Environmental Analysis
and Remediation (CEAR) facility at Saint Mary’s University using a Perkin Elmer 2400 II series
Elemental Analyser.
Synthesis of Phenylethynyl Tri(butyl)phosphonium Bromide 1
In a 20-mL scintillation vial, 2.00 g (11.0 mmol) of pale yellow coloured
bromophenylacetylene liquid were dissolved in 10 mL of pentane producing a pale yellow
coloured solution. To this solution, 2.24 g (2.76 mL, 11.1 mmol, 1.01 eq.) of colourless
tributylphosphine liquid were added dropwise, immediately producing a beige coloured
precipitate. Further addition of tributylphosphine produced a dark brown coloured viscous oil.
This mixture was left to stir overnight. The following day the stirring was stopped and the
pentane was decanted off, and contents of the flask were washed with a small amount of THF
and dried in vacuo, producing a dark brown coloured oil which crystallized upon standing
overnight. These crystals were not of suitable quality for X-ray diffraction, and so the brown
mixture of oil/crystals was triturated multiple times with ca. 5 mL of pentane, and dried in

Page 7 of 43
vacuo to produce a brown coloured powder. Attempts at producing crystals suitable for X-ray
diffraction from the brown powder using standard methods (evaporation, vapour diffusion,
solvent layering) were unsuccessful. Yield: 3.55 g (84%). m.p. (°C): 71.7–72.0. Anal. calc. for
C20H32PBr: C, 62.66; H, 8.41; N, 0.00%; Found: C, 61.15; H, 8.21; N, 0.02%. 31P{1H} NMR (121
MHz, CD2Cl2) δ: 21.5 ppm (s). 1H NMR (300 MHz, CD2Cl2) δ: 7.68–7.63 (m, 2H), 7.60 (tt, 3JHH = 7.5
Hz, 4JHH = 2.3 Hz, 1H), 7.48 ppm (t, 3JHH = 7.5 Hz, 2H), 2.87–2.78 (m, 6H), 1.69–1.66 (m, 6H), 1.57
(sextet, 3JHH = 7.4 Hz), 0.99 (t, 3JHH = 7.3 Hz). 13C{1H} NMR (75 MHz, CD2Cl2) δ: 133.2 (d, 4JCP = 2.2
Hz, ortho-(C6H5)), 132.7 (s, meta-(C6H5)), 129.3 (s, para-(C6H5)), 118.1 (d, 3JCP = 4.4 Hz, P-C≡C-C),
114.2 (d, 2JCP = 23.2 Hz, P-C≡C), 69.5 ppm (d, 1JCP = 149.5 Hz, P-C≡C), 24.7 (d, 2JCP = 5.5 Hz, CH2),
24.0 (d, 3JCP = 16.6 Hz, CH2), 22.6 (d, 1JCP = 53.3 Hz, CH2), 13.6 (s, CH3). IR (KBr pellet) ν: 3054 (w),
3013 (m), 2960 (vs), 2932 (vs), 2903 (s), 2869 (vs), 2179 (vs, C≡C), 1623 (w), 1489 (s), 1462 (s),
1446 (s), 1402 (m), 1382 (m), 1314 (w), 1283 (m), 1231 (m), 1206 (w), 1185 (w), 1158 (w), 1099
(s), 1027 (w), 1003 (w), 967 (w), 911 (s), 866 (s), 819 (m), 767 (vs), 726 (m), 695 (s), 635 (w), 540
(m), 466 (w), 446 cm-1 (w).
Synthesis of Phenylethynyl(triphenylphosphonium) Bromide 2
In a 100-mL round-bottomed flask, 4.00 g (22.1 mmol) of pale yellow coloured
bromophenylacetylene liquid were dissolved in 40 mL of pentane producing a pale yellow
coloured solution. To this solution, 5.80 g (22.1 mmol, 1.0 eq.) of colourless triphenylphosphine
granules were added, producing a pale yellow coloured mixture. This mixture was left to stir
overnight. The following day the stirring was stopped and the contents of the flask were

Page 8 of 43
allowed to settle, producing a pale yellow coloured solution over a tan coloured precipitate.
The pentane was decanted, and the residual solid was washed with pentane and dried in vacuo
to afford a pale yellow coloured powder which was recrystallized from dichloromethane
layered with pentane to afford pale yellow crystals.
Yield: 5.455 g (56 %). m.p. (°C): 209.6 – 210.2. Anal. calc. for C26H20PBr: C, 70.44; H, 4.55; N,
1
0.00%; Found: C, 70.25; H, 4.43; N, 0.02%. 31P{1H} NMR (121 MHz, CDCl3) δ: 6.5 ppm (s). H
NMR (300 MHz, CDCl3) δ: 7.97–7.79 (m, 17H), 7.66 (tt, 3JHH = 7.5 Hz, 4JHH = 2.3 Hz, 1H), 7.55 ppm
3
(t, JHH = 7.4 Hz, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ: 136.2 (d, 4JCP = 3.1 Hz, para-Ph3) 133.7 (d,
4JCP = 2.2 Hz, ortho-(C6H5)), 133.5 (s, meta-(C6H5)), 133.2 (d, 2JCP = 12.4 Hz, ortho-Ph3), 131.1 (d,
3JCP = 14.2 Hz, meta-Ph3), 129.4 (s, para-(C6H5)), 118.7 (d, 2JCP = 31.4 Hz, P-C≡C), 118.0 (d, 1JCP =
100.3 Hz, ipso-Ph3), 116.7 (d, 3JCP = 4.8 Hz, P-C≡C-Cipso), 69.0 ppm (d, 1JCP = 188.0 Hz, P-C≡C). IR
(KBr pellet) ν: 3046 (m), 3023 (m), 3014 (m), 2998 (m), 2985 (m), 2911 (w), 2584 (w), 2465 (w),
2167 (vs, C≡C), 2099 (m), 1810 (w), 1626 (w), 1584 (m), 1482 (m), 1317 (w), 1287 (w), 1261 (w),
1234 (w), 1185 (w), 1163 (w), 1113 (vs), 1025 (w), 997 (m), 930 (w), 871 (s), 840 (m), 803 (w,
br), 770 (s), 759 (s) 750 (m), 727 (vs), 701 (s), 687 (vs), 655 (m), 621 (w), 543 (s), 523 (vs), 495
(s), 460 cm-1 (w).
Synthesis of Phenylethynyl(tris(2,4,6-trimethoxyphenyl)-phosphonium) Bromide 5
In a 100-mL sealed reaction vessel, 0.882 g (1.66 mmol) of colourless tris(2,4,6-
trimethoxyphenyl)phosphine was suspended in 25 mL of heptane producing a colourless
suspension. To this suspension, 0.319 g (1.76 mmol, 1.06 eq.) of pale yellow coloured

Page 9 of 43
bromophenylacetylene was added, producing a pale yellow coloured mixture. This mixture was
warmed to 80 °C and left to stir for three days, monitoring by 31P{1H} NMR spectroscopy. The
reaction never reached completion after three days at 80 °C but a new signal appeared in the
31P{1H} NMR spectrum with an integration of 0.6:1 with respect to starting material. The stirring
was stopped and the contents of the flask were allowed to settle, producing a pale yellow
coloured mixture. The heptane was decanted off before suspending the contents of the flask in
ca. 10 mL of pentane and transferring to a vial. The pentane was decanted, and the residual
solid was washed with 3x15 mL portions of toluene and dried in vacuo to afford a colourless
powder. Yield: 0.099 g (8 %). Large colourless block-shaped crystals suitable for X-ray analysis
were obtained by dissolving the phosphonium salt in a 5:1 mixture of toluene and acetonitrile
and allowing the mixture to slowly evaporate. m.p.: 94.1-94.7 °C. Anal. calc. for C35H38O9PBr: C,
58.91; H, 5.37%. Found: C, 59.52; H, 5.70; N, 0.04%. 31P {1H} NMR (121 MHz, CD3CN) δ: -27.7
1
3
ppm (s). H NMR (300 MHz, CD3CN) δ: 7.56–7.48 (m, 3H, o-C6H4, p-C6H4), 7.46–7.40 (m, JHH
=
3
4
7.6 Hz, JHH = 6.8 Hz, 2H, m-C6H4), 6.28 (d, JHp = 5.8 Hz, 6H, m-ArH2), 3.88 (s, 9H, p-OCH3) 3.61
ppm (s, 18H, o-OCH3). 13C {1H} NMR (75 MHz, CD3CN) δ: 167.5 (s, p-ArC), 165.1 (d, 2JCP = 1.6 Hz,
o-ArC), 133.1 (d, 4JCP = 2.3 Hz, o-C6H5), 131.8 (s, p-C6H5), 129.9 (s, m-C6H5), 121.3 (d, 3JCP = 4.9 Hz,
i-C6H5), 102.9 (d, 2JCP = 36.6 Hz, P-C≡C), 93.0 (d, 3JCP = 7.5 Hz, m-ArC), 92.1 (d, 1JCP = 126.8 Hz, i-
ArC), 77.9 (d, 1JCP = 205.5 Hz, P-C≡C), 57.1 (s, o-OCH3), 56.7 ppm (s, p-OCH3). IR (KBr pellet) ν:
3181 (w), 3001 (m), 2940 (s), 2840 (m), 2186 (vs, C≡C), 2080 (w), 1937 (w), 1604 (vs), 1466 (vs),
1412 (vs), 1340 (vs), 1301 (m), 1234 (vs), 1208 (vs), 1161 (vs), 1127 (vs), 1098 (vs), 1024 (s), 949
(m), 917 (m), 858 (m), 816 (s), 762 (m), 735 (w), 693 (vs), 646 (w), 588 (w), 535 (m), 482 (vs),
444 cm-1 (m).

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Synthesis of ring closed phosphonium 1,4-oxazine 6a (C-H) and 6b (C-CH3)
Following the same procedure as for synthesis of 5 using instead toluene as the solvent, the
reaction was repeated at 105 °C using 0.300 g (1.66 mmol, 1 eq.) of 1-bromo-2-phenylacetylene
and 0.853 g (1.60 mmol, 0.96 eq.) of tris(2,4,6-trimethoxyphenyl)phosphine. The pale yellow
coloured reaction mixture was left to sit at 105 °C for three days without stirring. After this
time, a red coloured reaction mixture was present with red coloured crystals on the side of the
flask. These were analysed by X-ray diffraction and were revealed to be cyclised by-products.
The red coloured supernatant was decanted off, and the red coloured crystals were washed
with 3 x 15 mL portions of pentane and dissolved in 20 mL of acetonitrile. The red coloured
acetonitrile mixture was filtered through Celite, and the solvent was removed in vacuo to
produce a brown coloured semi-solid that was triturated with 10 mL of pentane to produce a
brown coloured powder containing a mixture of 3, 4a and 4b.
Yield: 0.76 g (in a 2.7:2.5:1 ratio from the 31P NMR spectrum for 5:6a:6b)
31P{1H} NMR (CD3CN): δ 6a -21.9 (s); 6b 0.0 ppm (s). These peaks were assigned based on the
similar ratio of 6a:6b in the single crystal X-ray structure.
Synthesis of Phenylethynyl(diphenyl(isopropyl)phosphonium) Bromide 7
In
a 100-mL sealed reaction vessel, 0.593 g (2.60 mmol) of colourless
diphenyl(isopropyl)phosphine were suspended in 25 mL of heptane. To this suspension, 0.437 g

Page 11 of 43
(2.41 mmol, 0.93 eq.) of pale yellow coloured bromophenylacetylene were added, producing a
pale yellow coloured mixture. This mixture was warmed to 95 °C and left to stir for six days to
ensure reaction completeness, but showed no visible changes after the first day. The stirring
was stopped and the contents of the flask were allowed to settle, producing a pale yellow
coloured mixture. The heptane was decanted off before suspending the contents of the flask in
ca. 10 mL of pentane and transferring to a vial. The pentane was decanted, and the residual
solid was washed with 3x15 mL portions of toluene and dried in vacuo to afford a colourless
powder. Yield: 0.320 g (32 %). Long needle-like colourless crystals suitable for X-ray analysis
were obtained by dissolving the phosphonium salt in a 5:1 mixture of toluene and acetonitrile
and allowing the mixture to slowly evaporate.
m.p.: 151.9–152.3°C. Anal. calc. for C23H22Br: C: 67.49; H, 5.42%. Found: C, 66.82; H, 5.25; N,
1
0.04%. 31P{1H} NMR (121 MHz, CD2Cl2): δ 24.0 ppm (s). H NMR (300 MHz, CD2Cl2): δ 8.35 (dd,
3
3
3JHP = 14.0 Hz, JHH = 7.6 Hz, 4H, o-C6H5), 7.86 (d, JHH = 7.6 Hz, 2H), 7.80–7.66 (m, 7H), 7.57 (t,
3
3
3JHH = 7.6 Hz 2H), 4.84 (oct, JHH = 7.0 Hz, 1H, CH(CH3)2), 1.39 ppm (dd, 2JHP = 21.5 Hz, JHH = 6.9
Hz, 6H, CH(CH3)2).13C{1H} NMR (121 MHz, CD2Cl2): δ 135.3 (d, 4JCP = 3.1 Hz, p-Ph2), 133.7 (d, 4JCP =
2.2 Hz, o-C6H5), 133.4 (s, p-C6H5) 133.1 (d, 2JCP = 11.8 Hz, o-Ph2), 130.6 (d, 3JCP = 13.8 Hz, m-Ph2),
3
129.5 (s, m-C6H5), 118.5 (d, 1JCP = 93.4 Hz, i-Ph2), 118.1 (d, 2JCP = 26.3 Hz, P-C≡C), 117.5 (d, JCP =
4.5 Hz, i-C6H5), 66.3 (d, 1JCP = 170.8 Hz, P-C≡C), 25.7 (d, 1JCP = 51.2 Hz, CH), 16.1 ppm (s, CH3).IR
(KBr pellet) ν: 3052 (m), 2974 (m), 2930 (m), 2834 (m), 2176 (vs, C≡C), 2098 (w), 1596 (m), 1485
(m), 1462 (m), 1439 (s), 1413 (w), 1388 (w), 1339 (w), 1265 (w), 1232 (m), 1208 (w), 1162 (m),
1110 (s), 1044 (w), 1025 (w), 997 (w), 871 (s), 811 (w), 762 (s), 725 (m), 692 (s), 626 (w), 542
(m), 519 (s), 480 cm-1 (w).

Page 12 of 43
Synthesis of 1,4-Bis((triphenylphosphonium)ethynyl)benzene dibromide 8
In a 20-mL scintillation vial, 0.166 g (0.584 mmol) of pale yellow coloured 1,4-
di(bromoethynyl)benzene powder were combined with 5 mL of acetonitrile producing a pale
yellow coloured mixture. To this mixture, 0.30 mL (1.20 mmol, 2.1 eq.) of colourless tributyl
phosphine were added via syringe to produce an orange coloured mixture. After ca. 10
minutes, the mixture turned black in colour and was left to stir overnight. The following day an
aliquot was removed for 31P{1H} NMR spectroscopy and showed multiple signals with a small
trace of the starting trinbutyl phosphine. Oily black coloured crystals suitable for X-ray
crystallography were obtained from a mixture of acetonitrile/diethyl ether (5 mL:5 mL) placed
in a -35 °C freezer overnight. Subsequent washings with pentane produced a black coloured
crystalline powder, however various by-products were still detected in the 31P{1H} NMR
spectrum.
Yield: 0.0646 g (16 %). m.p. (°C): 112.4–113.0. Anal. calc. for C34H58P2Br2: C, 59.31; H, 8.49; N,
0.00%; Found: C, 59.45; H, 8.54; N, 0.07%. 31P{1H} NMR (121 MHz, CD2Cl2) δ: 18.5 ppm (s, 2P).
1H NMR (300 MHz, CD2Cl2) δ: 7.73 (s, 4H, C6H4), 2.87–2.78 (m, 12H), 1.74–1.66 (m, 12H), 1.60–
3
1.48 (sextet, 3JHH = 7.3 Hz, 12H), 0.97 ppm (t, JHH = 7.3 Hz, 18H). 13C{1H} NMR (75 MHz, CD2Cl2)
δ: 133.5 (d, 4JCP = 2.2 Hz, ortho-(C6H4)), 121.5 (d, 3JCP = 4.4 Hz, ispo-(C6H4)), 111.5 (d, 2JCP = 22.7
Hz, P-C≡C), 73.5 (d, 1JCP = 146.1 Hz, P-C≡C), 24.5 (d, 2JCP = 6.1 Hz, CH2), 24.0 (d, 3JCP = 16.8 Hz,
CH2), 22.3 (d, 1JCP = 52.8 Hz, CH2), 13.5 ppm (s, CH3). IR (KBr pellet) ν: 2959 (vs), 2931 (vs), 2869
(vs), 2362 (w), 2182 (vs, C≡C), 1584 (m, br), 1498, (m), 1462 (s), 1402 (s), 1383 (s), 1344 (m),

Page 13 of 43
1315 (w), 1230 (s, br), 1128 (w), 1096 (vs), 1006 (m), 967 (m), 916 (vs), 851 (vs), 815 (s), 725 (s),
560 (m), 477 cm-1 (m, br).
Synthesis of 1,4-Bis((tributylphosphonium)ethynyl)benzene dibromide 9
In a 20-mL scintillation vial, 0.352 g (1.24 mmol) of pale yellow coloured 1,4-
di(bromoethynyl)benzene powder were dissolved in 10 mL of dichloromethane producing a
pale yellow coloured solution. To this solution, 0.651 g (2.48 mmol, 2.00 eq.) of colourless
triphenylphosphine granules were added, producing a pale yellow coloured mixture. After ca.
10 minutes, the mixture changes to a blue coloured solution. The reaction was analyzed by 31P
NMR spectroscopy when the sample is blue and it shows only starting material and product
present in solution. This mixture was left to stir overnight. The following day an orange
coloured solution remained. To this orange coloured solution, 10 mL of pentane were added to
facilitate the precipitation of the product. After stirring for ca. 10 minutes, the solvent was
decanted and the solid was dried in vacuo to afford the product as a yellow coloured powder
which was recrystallized from dichloromethane (3 mL) layered with pentane (15 mL) to produce
pale yellow coloured crystals.
Yield (crude): 0.9707 g (97 %). m.p. (°C): 106.0–106.8 (slight darkening), 210 (turns black,
decomposes).ii Anal. calc. for C34H58P2Br2: C, 68.33; H, 4.24; N, 0.00%; Found: C, 67.93; H, 4.17;
1
N, 0.02%. 31P{1H} NMR (121 MHz, CD2Cl2) δ: 7.1 ppm (s, 2P). H NMR (300 MHz, CD2Cl2) δ: 8.23
3
3
(s, 4H), 7.95–7.88 (m, 9H), 7.86 (t, JHH = 2.0 Hz, 1H), 7.42–7.39 (m, 2H), 7.26 ppm (t, JHH = 7.8
Hz, 1H). 13C{1H} NMR (75 MHz, CD2Cl2) δ: 136.5 (d, 4JCP = 3.2 Hz, para-Ph3) 134.7 (d, 4JCP = 2.2 Hz,
ortho-(C6H4)), 133.8 (d, 2JCP = 12.4 Hz, ortho-Ph3), 131.2 (d, 3JCP = 14.0 Hz, meta-Ph3), 121.5 (d,

Page 14 of 43
3JCP = 4.7 Hz, P-C≡C-C), 117.9 (d, 1JCP = 100.1 Hz, ipso-Ph3), 116.2 (d, 2JCP = 30.3 Hz, P-C≡C), 72.7
ppm (d, 1JCP = 184.0 Hz, P-C≡C). IR (KBr pellet) ν: 3046 (m), 3004 (m), 2687 (w), 2580 (w), 2465
(w), 2317 (w), 2177 (vs, C≡C), 1615 (m, br), 1582 (m), 1480 (m), 1438 (vs), 1400 (w), 1360 (m),
1312 (w), 1282 (m), 1238 (w), 1184 (w), 1109 (vs), 1018 (w), 996 (m), 934 (w), 857 (vs), 754 (s),
727 (vs), 688 (vs), 616 (w), 561 (m), 526 cm-1 (vs).
X-ray Crystallography
Crystals of compounds 1,2 and 5-9 were mounted from Paratone-N oil on an
appropriately sized MiTeGen MicroMount. The data were collected on a Bruker APEX II charge-
coupled-device (CCD) diffractometer, with an Oxford 700 Cryocool sample cooling device and
all samples were cooled to 125 K. The instrument was equipped with graphite-monochromated
Mo Kα radiation (λ = 0.71073 Å; 30 mA, 50 mV), with MonoCap X-ray source optics. For data
collection, four ω-scan frame series were collected with 0.5° wide scans, 5 to 60 second frames
depending on the sample and 366 frames per series at varying φ angles (φ = 0°, 90°, 180°,
270°). Data collection, unit cell refinement, data processing and multi-scan absorption
correction were applied using the Bruker APEX II or APEXIII software packages. The structures
were solved using SHELXT30 and all non-hydrogen atoms were refined anisotropically using a
combination of shelXle31 and OLEX232 graphical user interfaces and SHELXL.33 Unless otherwise
noted, all hydrogen atom positions were idealized and rode on the atom to which they were
attached. The final refinement included anisotropic temperature factors on all non- hydrogen
atoms. Details of crystal data, data collection, and structure refinement are listed in Table 1. All

Page 15 of 43
figures were made using ORTEP-3 for Windows.34 During the refinement of 5, one molecule was
present along a three-fold axis. This caused disorder in the phenyl ring. This was modelled by
fixing the site occupancies of C36, C37, and C38 to 0.3333, and 0.5000 for C39 and C40. The
atoms P2, Br1, and Br3 were also part of this disorder and their occupancies were fixed at
0.3333, 0.1667, and 0.1667, respectively. Toluene had co-crystallized with 3 and also exhibited
disorder along a three-fold axis. C51, C52, and C53 were part of this disorder and were
modelled using the PART-1 command. The site occupancy for C53 was fixed to 0.3333. The
thermal ellipsoids of C10, O1, and C15 were restrained to be approximately isotropic using the
ISOR command. During the refinement of 6a+b, substitutional disorder was encountered in the
atoms attached to C1 (either H1 or C35). This was modelled using the PART command and the
site occupancies were found to give the best refinement with a 0.75 occupancy for H1 and a
0.25 occupancy for the C35 methyl group. Disorder was also modelled for some of the methoxy
substituents using the PART command, with site occupancies freely refined with a 0.923
occupancy for C16a and 0.076 occupancy for C16b, and a 0.886 occupancy for C25a and 0.114
occupancy for C25b. The anisotropic displacement paramters of C16a, C16b, C1, and C35 were
constrained using the EADP command. During the refinement of 8, it was noted that the butyl
groups C1-C4, C5-C8 and C9-C12 exhibited two component disorder and the different
components of the disorder were separated using the PART command. Site occupancies were
allowed to freely refine to give a 0.800 occupancy for C1a-C4a and 0.200 occupancy for C1b-
C4b, a 0.601 occupancy for C5a-C8a and a 0.399 occupancy for C5b-C8b, and a 0.157 occupancy
for C9a-C12a and a 0.843 occupancy for C9b-C12b. Rigid bond restraints were applied using the
RIGU command. The thermal ellipsoid of C7B was restrained to be approximately isotropic

Page 16 of 43
using the ISOR command. For the butyl groups, P-C bond lengths, 1,2-distances, and 1,3-
distances were restrained appropriately using the DFIX command. During the refinement of 9,
disorder was encountered in a molecule of co-crystallized dichloromethane. Different
components of the disorder were separated using the PART command. Site occupancies were
allowed to freely refine to give occupancies of 0.936 and 0.064 for each component. Distances
between C-Cl were restrained to be approximately equal using the SADI command. Tables of
bond lengths and angles are given in the Supporting Information. CCDC 1526619–1526625
contain the supplementary crystallographic data for complexes 1,2 and 5–9. These data can be
obtained free of charge from the Cambridge Crystallographic Database Centre via
https://summary.ccdc.cam.ac.uk/structure-summary-form.
Electronic structure calculations
Calculations on the model cations [Ph-C≡C-PPh3]+ and [Ph-C≡C-PMe3]+ were performed using
Gaussian09W.35 Structures were optimized at the B3LYP/6-31g(d) level of theory36-39 and
stationary points were verified using frequency calculations. For the scan of the P-C≡C angles of
the model compound [Ph-C≡C-PMe3]+, the angle was locked at 1° intervals over a 75° range
from the optimized angle of 179.57° and at each step, the rest of the molecule was allowed to
optimize.
Results and discussion
Mono(ethynyl)phosphonium salts

Page 17 of 43
Reaction between bromophenylacetylene and tri(butyl)phosphine) or triphenylphosphine in
pentane yielded the previously known phenylethynylphosphonium bromides 1 and 2 in high to
moderate yields (84% and 56%, respectively). Pentane was chosen as the reaction medium to
facilitate direct precipitation of the product. This worked well for 2, however 1 produced an oil
that required multiple triturations with pentane before yielding a fine brown coloured powder.
1
To the best of our knowledge, 1 has only been characterized by H NMR spectroscopy with
vague peak assignments, IR spectroscopy with only the acetylenic vibration reported, melting
point, and by elemental analysis.3 It has not been previously characterised by 13C{1H} and
31P{1H} NMR spectroscopy or structurally by X-ray crystallography, and no cyclic voltammetry
has been attempted. Taking into consideration that publication standards have changed, and
that the objective of the earlier reports was to evaluate the kinetics of the formation of 1, it
seemed appropriate to revaluate and expand upon the characterization data available.
Compound 2 has more characterization data available; 1H, 13C{1H}, and 31P{1H} NMR
spectroscopic properties have been studied18,22, and have often been supplemented by IR
spectroscopy and melting point3,18,22, and cyclic voltammetry studies have been done as well.40
These data will be combined and compared to our own but will not be discussed in detail.
Discussion will be limited only to the new structural information obtained through single crystal
X-ray diffraction. 31P and 13C NMR chemical shifts and coupling constants, IR C≡C stretches, and
P-C≡C bond angles for compound 1, 2, 5-9 have been compiled in Table 1.

Page 18 of 43
1
The H NMR spectrum of 1 was collected in CD2Cl2 displayed no unusual characteristics
and was similar to previous reports in CDCl3.3 The sample was collected in CD2Cl2 to compare
spectroscopic properties with the related trimethylphosphine derivative 3 which was also
measured in CD2Cl2.17 The methylene bound directly to phosphorus was detected as a multiplet
1
2
in the H NMR spectrum (δ 2.87–2.78 ppm, JHP = 14.6 Hz) and is similar to that of the methyl
2
groups found in 3 (δ 2.57 ppm, JHP = 15.2 Hz).17 The remaining methylene resonances appear
as a multiplet (δ 1.79–1.65 ppm), and as a sextet (δ 1.56 ppm, 3JHH = 7.2 Hz) while the terminal
methyl group was identified as a triplet (δ 0.99 ppm, 3JHH = 7.2 Hz). In the aromatic region the o-
ArH (δ 7.65 ppm, 3JHH = 7.8 Hz), m-ArH (δ 7.48 ppm, 3JHH = 7.5 Hz), and p-ArH (δ 7.59 ppm, 3JHH
=
7.6 Hz) resonances are visible as multiplets and appear in a 2:1:2 ratio. These were assigned on
the basis of their integration values as well as the degree of coupling observed. The 13C{1H}
NMR spectrum exhibited the acetylenic carbon resonances appear as two sets of doublets (δ
2
1
114.2 ppm, JCP = 23.2 Hz and 69.5 ppm, JCP = 149.5 Hz), and are similar to other reported
ethynylphosphonium salts.17,22 The remaining signals were assigned on the based on the
magnitude of their JCP values22, and using the 13C{1H} DEPTQ experiment. The 31P{1H} NMR
spectrum of 1 displayed a singlet resonance (δ 21.5 ppm). Other phosphorus-containing
impurities could be seen near the baseline, but could not be identified on the basis of their 31P
chemical shifts. The acetylenic vibration (ν: 2179 cm-1) matches the literature3, while the
melting point (71.7–72 °C) was considerably higher than previously reported (57–59 °C).
In the powder form, 1 could not be recrystallized using routine techniques. Crystals of 1
were instead obtained by slow reagent diffusion in pentane (see Experimental section for
details). Compound 1 crystallizes in the monoclinic space group P21/c as colourless rectangular

Page 19 of 43
blocks, and features only one molecule in the asymmetric unit (Figure 1). The structure of 1 is
consistent with the observed spectroscopic data and features a tetra-coordinated phosphorus
cation with a bromide counter anion nested between three butyl groups. The P1-C1 and C1-C2
bond lengths were found to be 1.739(2) Å and 1.197(3) Å respectively and are similar to the
measurements found in 3 (1.739(3) Å and 1.202(4) Å respectively)17, and 4 (1.719(2) Å and
1.190(2) Å).6
Crystals of 2 were obtained by layering a concentrated dichloromethane solution with pentane.
Compound 2 crystallizes in the orthorhombic space group Pbca as colourless rectangular blocks,
and features only one molecule in the asymmetric unit (Figure 2). The structure of 2 is also
consistent with spectroscopic data and is structurally similar to 1. The P1-C1 and C1-C2 bond
lengths were found to be 1.727(2) Å and 1.200(3) Å. As previously mentioned, recent evidence
suggests that the phenylacetylene fragment of 2 is responsible for anticancer activity,12-14 so
the overall length of the phenylacetylene fragment determined by the distance between P1-C6
was measured and found to be 7.106(2) Å. When the same measurement is done for 1 it is
found that the distance between P1-C6 is 7.045(3) Å, indicating that modification of the groups
attached to phosphorus causes a change in the overall P-C≡C-Ph length.
Several attempts were made at expanding the library of known derivatives of 2 with
varied aryl substituents, however these were unsuccessful. Reactions involving sterically
hindered or electron deficient phosphines (PMes3, (Mes = 2,4,6-trimethylphenyl), P(o-Tol)3 (o-
Tol = 2-methyl-phenyl), and P(C6F5)3) were attempted at 60 °C in either toluene or heptane, and

Page 20 of 43
with or without silver triflate added to abstract the bromide, but were unsuccessful in
producing the desired ethynylphosphonium salts; reactivity was observed but the products
could
not
be
unambiguously
identified.
The
electron-rich
tris(2,4,6-
trimethoxyphenyl)phosphine (TMPP) also did not react at room temperature in toluene,
however reactivity was observed at elevated temperatures. When TMPP was combined with 1-
bromo-2-phenylacetyelene in heptane and heated to 80 °C for 3 days, the ethynylphosphonium
salt 5 was obtained in only 8% isolated yield (Scheme 3). Compound 5 was characterised by
multinuclear NMR and IR spectroscopies, melting point determination, and X-ray
crystallography (Figure 3). Analogous to triarylphosphines, the 31P{1H} chemical shift of 5 is
considerably lower in frequency than related ethynylphosphonium salts, appearing as a singlet
1
(
Δ
-27.7 ppm
)
when measured in CD3CN. Collectively, the resonances in the H NMR spectrum
attributed to the TMPP moiety are shifted to a slightly higher frequency than the parent
phosphine41, while the acetylenic carbon resonances appear as two sets of doublets (δ 102.9
1
ppm, 2JCP = 37.0 Hz and 77.9 ppm, JCP = 205.5 Hz). Further evidence for a carbon-carbon triple
bond is given by a strong signal in the IR spectrum (ν: 2186 cm-1), which is only slightly higher in
energy than 2 (ν: 2167 cm-1), showing a significant alteration in the C≡C bond strength due to
the TMPP.
It was speculated that poor solubility was the reason for such a slow conversion, so in an
attempt to accelerate the reaction toluene was chosen as the reaction medium for its higher
boiling point and solvent polarity. When the same reaction was performed in toluene at 105 °C
for 3 days, the initial formation of the ethynylphosphonium salt 5 occurred and partially

Page 21 of 43
underwent an intramolecular cyclization to form two additional products. The
phosphoniapyrans 6a and 6b were first identified crystallographically and co-crystallized in a
3:1 ratio, and were later identified with similar ratios (2.5:1) using 31P and 31P {1H} NMR
spectroscopies (6a δ -21.9 ppm, 6b δ 0.0 ppm). The most probable source of 6b is the initial
formation of 5, followed by an intramolecular cyclization via nucleophilic attack at the β-carbon
of the acetylene by a methoxy group in the ortho position, before finally undergoing a 1,3-shift
of the methyl group to the vinylic position. Attempts at elucidating the pathway leading to the
formation of 6a have been unsuccessful thus far; an initial hypothesis was that 6a formed after
an intermediate reacted with the solvent. To test this, the reaction was repeated in deuterated
toluene, however no deuterium incorporation was evident thereby eliminating this as a
possibility. A careful analysis of a solution of 5 in toluene-d8 heated for 5 days in a sealed NMR
tube did not reveal any methane, ethane, or ethene that may form from the lost CH2 fragment
in 6a. A pure sample of 5 was heated in toluene-d8 and the cyclization did occur, proving that
this is indeed the intermediate to the cyclization product 6a/6b and that the starting materials
or reaction intermediates are not needed to promote the reaction.
Structurally 6a and 6b differ by only a hydrogen atom or methyl group attached to C1 and
co-crystallize in the monoclinic space group P21/n as yellow rectangular blocks (Figure 4). The
phosphorus centre deviates significantly from an ideal tetrahedral geometry, with the most
acute angles being between C1-P1-C27 (101.42(13)°) and C1-P1-C9 (105.87(13)°). The
phosphorus-carbon bond lengths are all similar, however a slight shortening was noted for P1-

Page 22 of 43
C1 (1.763(3) Å) and P1-C27 (1.766(3) Å) when compared to P1-C9 (1.798(3) Å) and P1-C18
(1.790(3) Å) of the non-cyclized aryl rings. These measurements are similar to those found in
the only other structurally characterised phosphoniapyran in the literature.42
Finally, the mixed alkyl/aryl phosphine, P(iPr)Ph2 was reacted with bromophenylaceytylene
over several days in heptane at 95°C. Upon workup, the ethynylphosphonium salt 7 was
isolated in moderate yield. The 31P NMR chemical shift (δ 24.0 ppm) is similar to that of the
2
tributyl derivative 1 and the ethynyl signals in the 13C NMR spectrum (δ 118.1 ppm, JCP = 26.3
1
Hz and 66.3 ppm, JCP = 170.8 Hz) are similar to those in 1 and 2. The ethynyl signal in the IR
spectrum appears at 2176 cm-1 and is in line with the other derivatives.
Compound 7 crystallizes in the orthorhombic space group Pbca as long colourless needles
and contains three molecules in the asymmetric unit in an alternating head-to-tail arrangement
(Figure 5). Since all three entities in the asymmetric unit are similar, discussion will be limited to
one. The P-C(sp) bond length of 1.733(3) Å is between the corresponding distances in 1 and 2.
The P-C≡C fragment in all three molecules vary from ca. 167° to 175°, implying that this angle in
alkynylphosphonium salts is highly dependent on crystal packing and less dependent on the
electronic structure of the molecule. Electronic structure calculations confirm this vida infra.
Bis(ethynyl)phosphonium salts

Page 23 of 43
For reasons previously stated, current synthetic routes for bis(ethynylphosphonium)
salts are undesirable as they are somewhat convoluted. An alternative, atom-economical
approach was found by reacting the tertiary phosphines P(n-Bu)3 and PPh3 with 1,4-
(dibromoethynyl)benzene in either acetonitrile or dichloromethane, giving the new
bis(ethynylphosphonium) salts 1,4-[(R3PC2)2C6H4]Br2 (R = n-Bu, 8; Ph, 9) in 16% and 97% isolated
yields respectively. Both 8 and 9 were fully characterised using multinuclear NMR spectroscopy,
IR spectroscopy, X-ray crystallography, cyclic voltammetry, melting point determination, and
elemental analysis. These molecules displayed similar spectroscopic properties and structural
parameters as their analogous monophenylethynyl derivatives 1 and 2.
All attempts at the synthesis of 8 using dichloromethane as a solvent produced a
complex mixture of phosphorus-containing products that could not be identified on the basis of
their 31P NMR chemical shifts. Employing acetonitrile as a solvent produced a similar mixture of
products, although with higher amounts of 8. These impurities could not be completely
removed by multiple pentane washings or by recrystallization and efforts to obtain high purity
material severely impacted the isolated yield. The 31P{1H} NMR spectrum displayed a singlet
1
resonance (δ 18.5 ppm) in CD2Cl2, highlighting the symmetrical nature of 8. In the H NMR
spectrum, the symmetrical nature of the molecules is highlighted by the central aromatic
exhibiting a singlet resonance (δ 7.79 ppm). The n-butyl methylene resonances displayed
2
complex multiplet patterns (δ 2.87–2.78 ppm, JHP = 14.6 Hz, 1.74–1.62 ppm, and 1.60–1.48
3
ppm) and a characteristic triplet (δ 0.96 ppm, JHH = 7.2 Hz) was observed for the terminal
methyl groups. The integration values for these peaks did not match the expected structure and

Page 24 of 43
this is most likely caused from the multiple impurities clearly present in both the 1H and 31P{1H}
NMR spectra. The butyl groups could still be assigned reliably based on characteristics similar to
1b. The acetylenic carbons were identified by two doublets in the 13C{1H} NMR spectrum (δ
111.5 ppm, 2JCP = 22.7 Hz and 73.5 ppm, 1JCP = 146.1 Hz), and also by a strong vibration in the IR
spectrum (ν: 2182 cm-1) and are consistent with those measured in the monophosphonium
analogue 1.
Long, yellow coloured needle-shaped crystals of 8 suitable for X-ray diffraction were
obtained by dissolving the black coloured powder in a 1:1 mixture of acetonitrile and diethyl
ether and storing in a -35 °C freezer overnight (Figure 6). Compound 8 crystallizes in the
monoclinic space group P21/c and features one half of the molecule in the asymmetric unit.
Considerably more disorder was encountered in the n-butyl groups of 8 relative to 1. The P1-
C13 and C13-C14 bond lengths were found to be 1.735(6) Å and 1.208(6) Å respectively, and are
similar to the related monoethynyl species 1 and 2, and those of the literature.6,17 No
structurally characterised bis(ethynyl-phosphonium) salts were available for comparison in the
literature, however these parameters were found to be similar to 9 (vide infra).
The synthesis of 9 was much more straightforward and allowed for the use of
dichloromethane as the solvent followed by the addition of pentane to facilitate precipitation
of the bisphosphonium salt. Spectroscopically 9 is similar to 8 with a strong diagnostic
acetylenic vibration in the IR spectrum (ν: 2177 cm-1). The 13C{1H} NMR spectrum (δ 116.2 ppm,

Page 25 of 43
1
2JCP = 30.3 Hz and 72.7 ppm, JCP = 184.0 Hz), while a singlet is observed in the 31P{1H} NMR
1
spectrum (δ 7.1 ppm). The bridging aromatic ring was clearly visible as a singlet in the H NMR
spectrum (δ 8.23 ppm), again highlighting the symmetric nature of the molecule.
Crystals of 9 suitable for X-ray diffraction were obtained by layering a concentrated
dichloromethane solution with pentane (Figure 7). Compound 9 crystallizes in the monoclinic
space group P21/c and features one half of the molecule in the asymmetric unit. The P1-C1 and
C1-C12 bond lengths were found to be 1.743(5) Å and 1.196(7) Å respectively, and are similar to
the other derivatives.
Electronic Structure Calculations
In the report of the ethynyl phosphonium salt, [Ph-C≡C-PMe3]Br by Schuster and
Schmidbaur17, the canonical structures shown in Scheme 4 were discussed as possibly having an
impact on the properties of the molecules. In our investigation of this class of molecules we
performed some electronic structure calculations to see the distribution of charge in these
molecules. Natural population analysis (NPA) calculations on the [Ph-C≡C-PPh3] cation show
that there is a significant contributions of both the left and middle canonical structures
(Scheme 4), where the positive charge is located on the phosphorus atom (left) or the positive
charge is located on the acetylenic β-carbon (right).

Page 26 of 43
We also noted a significant deviation of the P-C≡C angle in the solid state structures of
the ethynyl phosphonium salts; these angles range from 163.1(2)° for 1 to 175.9(3)° for 7 and
even in the solid state structure for compound 7, the three independent molecules in the
asymmetric unit have P-C≡C angles that range from 167.1(3)° to 175.9(3)°. This prompted us to
investigate the energetic impact of the P-C≡C angle when it deviates from linearity. A scan of
the P-C≡C angles in the model caꢀon, [Ph-C≡C-PMe3]+, shows that decreasing the P-C≡C angle
from the fully optimized angle of 179.57° to 139.57 (40° total) there is only a 4.7 kcal/mol
energetic penalty for this deviation, again reinforcing that in the solid state, these angles are
impacted by crystal packing forces (Figure 8).
Conclusions
The ethynylphosphonium salts 1 and 2 were reinvestigated and the newly reported
structural information indicated that exchanging alkyl and aryl groups bound to phosphorus
leads to significant structural differences in the phenylacetylene fragment. Several attempts at
diversifying the steric or electronic properties of the phosphorus were also made, but were
mostly unsuccessful in producing the desired ethynylphosphonium salts. When the electron-
rich, sterically hindered tris(2,4,6-trimethoxyphenyl)phosphine was used reactivity was only
observed at elevated temperatures, however this produced only a minimal amount of 5 in
heptane, or a mixture of 5 with the cyclized by-products 6a,b. IR spectroscopy demonstrated
similarities in the energy of the acetylenic vibrations between 2 and 5, indicating that

Page 27 of 43
modification of the aryl rings with electron-donating substituents also produced only minor
changes in the acetylene fragment.
A new, more sustainable, synthetic route to the related bis(ethynylphosphonium) salts
has also been discovered and the newly synthesized derivatives 8 and 9 have been reported.
These compounds exhibit similar spectroscopic and structural properties to their related mono-
substituted derivatives, and are the first bis(ethynylphosphonium) salts to be structurally
characterised using X-ray crystallography.
Acknowledgements
We thank the Natural Sciences and Engineering Research Council of Canada (through the
Discovery Grants Program to JDM). JDM acknowledges support from the Canadian Foundation
for Innovation and the Nova Scotia Research and Innovation Trust Fund as well as various
support from Saint Mary’s University during the sabbatical in which this manuscript was
written.
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