Synthesis and characterization of alkyltris(2-pyridyl)phosphonium salts

Article abstract of DOI:10.1080/10426500500328871

Alkytris(2-pyridyl)phosphonium salts [(2-Py)₃PR]X 1 [1a, R = Et, X = Br; 1b, R = Pr, X = Br; 1c, R = Bu, X = Br; 1d, R = CH₂Ph, X = Br; 1e, R = CH₂Ph, X = Cl] were synthesised from (2-Py)₃P and an excess of RCl. 1c and 1e were found to rapidly decompose in hot acetone to 2,2′-bipyridinium(+1) bromide 2 and (2-Py)P(O)(CH₂Ph)C(OH) Me₂ 3, respectively. A reaction mechanism for both products is proposed. All compounds were fully characterized, including X-ray crystallography for 1a and 3 with 1a being the first representative of this class of compounds characterized by this technique. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500500328871

Phosphorus, Sulfur, and Silicon, 181:1403–1418, 2006
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500500328871
Synthesis and Characterization
of Alkyltris(2-pyridyl)phosphonium Salts
Richard J. Bowen
Manuel A. Fernandes
Patricia W. Gitari
Marcus Layh
Molecular Sciences Institute, School of Chemistry, University of the
Witwatersrand, Johannesburg, South Africa
Alkytris(2-pyridyl)phosphonium salts [(2-Py)3 PR]X 1 [1a, R = Et, X = Br; 1b, R =
Pr, X = Br; 1c, R = Bu, X = Br; 1d, R = CH2Ph, X = Br; 1e, R = CH2 Ph, X =
Cl] were synthesised from (2-Py)3 P and an excess of RCl. 1c and 1e were found
to rapidly decompose in hot acetone to 2,2ꢀ-bipyridinium(+1) bromide 2 and (2-
Py)P(O)(CH2 Ph)C(OH)Me2 3, respectively. A reaction mechanism for both products
is proposed. All compounds were fully characterized, including X-ray crystallogra-
phy for 1a and 3 with 1a being the first representative of this class of compounds
characterized by this technique.
Keywords 2-Pyridylphosphonium salts; α-hydroxyphosphine oxide; hydrolysis; X-ray
INTRODUCTION
The antitumor activity of a range of lipophilic cations including
Rhodamine-123,1 dequalinium1,2 AA1,3 bisquaternary ammo-
nium heterocycles,4 MKT-077,5 tetrahedral bidentate phosphine
Au(I) complexes,6 and alkyltriarylphosphonium salts7 has been
well established. An antimitochondrial mode of action as a re-
sult of their lipophilic cationic character and consequent uptake
into the mitochondria has been suggested. For several types of
lipophilic cations (e.g., Au(dnpype)+2 , n = 2–4, dnpype = 1,2-bis(di-n-
pyridylphosphino)ethane6; Ph4PCl8) it was demonstrated that the
Received April 22, 2005; accepted July 28, 2005.
The authors thank the Cancer Association of South Africa (CANSA), the Technology
and Human Resources for Industry (THRIP), the Claude Harris Leon Foundation, and
the University of the Witwatersrand for financial support.
Address correspondence to Marcus Layh, Molecular Sciences Institute, School of
Chemistry, University of the Witwaterstrand, Private Bag 3, Wits, Johannesburg, 2050
South Africa. E-mail: layhms@googlemail.com
1403

1404
R. J. Bowen et al.
selectivity of compounds for tumor cells was increased by modifying
the lipophilic/hydrophilic balance and increasing their hydrophilicity.
The replacement of phenyl groups in [Au(dppe)2]+ [dppe = 1,2-bis-
(diphenylphosphino)ethane]6 by hydrophilic pyridyl groups was found
to be particularly promising as the systematic variation of the position
of the N atom in the pyridyl ring modulated the lipophilicity and
increased the selectivity for tumor cells versus normal cells. The
lipophilic cation [Au(dppe)2]+ was in contrast found to be nonselective
and toxic to mitochondria of all cells,6 while the related hydrophilic ca-
tion [Au(dpmaa)2]+ [dpmaa = 1,2-bis(diphenyphosphino)maleic acid]9
showed a high water solubility and very limited activity. Following
the previously mentioned study on triarylalkylphosphonium salts
by Rideout et al.,7 we had previously synthesized a series of cyclic
phosphonium salts10 that were, however, found to be unstable in water
or biological fluids. It was therefore decided to investigate the potential
of tris(2-pyridyl)alkylphosphonium salts that so far have found very
limited interest in the chemical literature11 as anticancer drugs. This
manuscript describes the synthesis and characterization of a series of
tris(2-pyridyl)alkylphosphonium bromides.
SYNTHESIS AND PROPERTIES OF [(2-Py) PR]X
3
The reaction of (2-Py)3P11b with an excess of alkyl halide under reflux
conditions and reaction times of several hours yielded the pyridylphos-
phonium salts [(2-Py)3PR]X 1 ((i) in Scheme 1). In the case of the less
reactive PhBr, product formation was not observed, and extended re-
action times in the presence of air led instead to the formation of (2-
Py)3PO that was previously obtained from alkoxyphosphonium salts via
an Arbuzov reaction.12 In agreement with previous reports for tertiary
SCHEME 1 Synthesis of tris(2-pyridyl)phosphonium salts.

Alkyltris(2-Pyridyl)phosphonium Salts
1405
phosphines,11,13a there was no significant quaternization at the nitro-
gen atom (there were only minor peaks in the 31P-NMR spectrum of the
crude products). Preferential quaternization at the nitrogen atom has
previously mainly been observed for primary phosphines RPH2 and in
cases were strong Brønsted acids (H+) were used as electrophiles.13 This
behavior is a reflection of the higher nucleophilicity of tertiary phos-
phines and the higher basicity of amines. Attempts to synthesise 3-Py
and 4-Py analogues of 1 under similar reaction conditions as described
for (2-Py)3P were unsuccessful. Monitoring by 31P-NMR spectroscopy
showed that reactions were slower for EtBr, and prolonged heating re-
sulted in a mixture of products that could not be separated. A similar
behavior was observed for the reaction of (3-Py)3P with PhCH2X (X =
Br, Cl), while in the case of (4-Py)3P and PhCH2Cl, a fast reaction re-
sulted in an unidentifiable green paste.
Phosphonium salts were colorless (1a, 1b) or yellow (1c–1e) solids
that were soluble in polar solvents such as acetone (not 1d, 1e) or
methanol (not 1e, due to rapid decomposition) and could be recrys-
tallized from a mixture of polar and nonpolar solvents. When 1c or 1e
were briefly heated in acetone to increase their solubility, they were
found to decompose rapidly to the 2,2ꢀ-bipyridinium(+1) bromide 2
((ii) in Scheme 1) and/or the phosphine oxide 3 ((iii) in Scheme 1),
SCHEME 2 Proposed reaction mechanism for the formation of 2 and 3 (c. f.
reference 16).

1406
R. J. Bowen et al.
respectively, which were both fully characterized including X-ray crys-
tallography (the crystal structure of 2 was reported in ref. 14). Uchida
et al.11d,12,15,16 have previously reported in closely related systems the
formation of bipyridines from (1) the reaction of 2-pyridylphosphines
or 2-pyridylphosphine oxides and chlorine followed by slow hydrolysis
in alcohol or water and (2) the slow reaction of pyridylphosphine ox-
ides or 1d with H2O (CH3OH) or H2O(CH3OH)/HCl, respectively. In
this work, the same authors proposed a reaction mechanism (Scheme
211d,16) that accounts for the formation of 2 and 3. It involves the nu-
cleophilic addition of water to the phosphonium salt to give a penta-
coordinate phosphorous intermediate ((i) in Scheme 2), followed by pro-
ton migration to the nitrogen atom of a pyridyl ring ((ii) in Scheme 2)
and reductive elimination of the bipyridine ((iii) in Scheme 2) to give
the phosphinic acid (2-Py)PR(OH) and its thermodynamically favored
tautomer (2-Py)P(O)(R)H ((iv) in Scheme 2). The isolation of 3 lends
further support to this reaction mechanism as phosphinous acids such
as (2-Py)P(O)(R)H are known to rapidly add to ketones and aldehydes
to yield α-hydroxyphosphine oxides ((v) in Scheme 2) (reference 17 and
references therein).
The hydrolytic instability of the phosphonium salts as evident from
the rapid reaction in wet acetone was further confirmed by NMR exper-
iments that showed that all compounds decomposed completely within
24 h in D2O or DMSO/foetal calf serum to a number of unidentified prod-
ucts. Phosphine oxides similar to 3 are likely to be major components
of the mixture based on signals in the 31P NMR spectrum (δ 31.1–39.2)
close to that of 3 (δ 39.0). This lack of stability precluded further biolog-
ical testing.
Table I summarizes selected NMR spectroscopic data of pyridyl
phosphorous compounds together with their phenyl analogues. The
13C NMR signals of the ipso-C atoms of the pyridyl compounds
were shielded in comparison to the phenyl derivatives as was ex-
pected from the available data for substituted pyridines and benzenes,
respectively.22 The 31P NMR values of the pyridyl derivatives were in
contrast deshielded by more than δ = 10 if compared to the phenyl
analogues. The coupling constant [1 J(CP), 2 J(HP)] of the alkyl sub-
stituents of the phosphonium salts were essentially the same in all
compounds and significantly smaller than those of corresponding aryl
groups. This has previously been attributed to the increased s char-
acter and electronegativity of the ipso-C atoms of the aryl substi-
tuents.20a,23 The latter argument may also explain the much higher
coupling constants of pyridyl derivatives (the presence of N should
increase the electronegativity of the ipso-C) as compared to phenyl
analogues.

Alkyltris(2-Pyridyl)phosphonium Salts
1407
TABLE I Selected NMR-Spectroscopic Data (ppm, Hz) of 2-Pyridyl
Phosphorous Compounds and Their Phenyl Analogues
Compound
δ (31P) δ (13C, ipso-Ar) 1 J[C(R)-P] 1 J[C(Ar)-P] 2 J(H-P)
[(2-Py)3PEt]Br
15.4
13.2
13.5
11.8
12.0
14.8
39.0
142.8
142.4
142.9
142.8
143.1
154.7
155.6
50.7
48.9
49.4
45.9
45.0
—
115.0
114.9
115.0
115.2
115.2
133.1
106.5
14.3
m
m
15.5
15.5
—
[(2-Py)3PPrn]Br
[(2-Py)3PBun]Br
[(2-Py)3P(CH2Ph)]Br
[(2-Py)3P(CH2Ph)]Cl
(2-Py)3PO
(2-Py)P(O)(CH2Ph)
58.4
13.6
CH(OH)Me2
[Ph3PEt]Br18
[Ph3PPrn]Br19
[Ph3PBun]Br18
3
26.8
24.1
25.8
23.6
23.2
29.3
117.3
118.3
117.9
—
118.5
132.8
51.0
50.0
49.8
—
47.2
—
85.9
—
85.9
—
85.6
103.5
12.6
—
—
—
—
[Ph3P(CH2Ph)]Br19a
[Ph3P(CH2Ph)]Cl20
Ph3PO21
—
SOLID STATE STRUCTURES OF 1A AND 3
Compound 1a is, to the best of our knowledge, the first example of a
crystallographically characterized tris(2-pyridyl)phosphonium salt. It
¯
crystallizes in the triclinic space group P1 with one ion pair in the asym-
metric unit (Figure 1). The coordination of the phosphorous atom in the
cation is essentially tetrahedral showing bond distances and angles
(Table II) that are comparable to those in related triphenylphospho-
nium salts such as [Ph3PEt]I3,24 [Ph3PCH2Ph]Br,25 [Ph3PMe]X (X =
BF4, ClO426, X = I3−),27 or [Ph4P]Br·H2O.28 In contrast to the latter
class of compounds, there are, however, in 1a additional intermolecular
. . .
close contacts (2 × C-H N) between cations and between the cation
. . .
and anion ( 4× C-H Br), resulting in a layer structure (Table III, Fig-
ure 2). Layers are further connected via two additional, slightly longer,
. . .
. . .
˚
. . .
˚
C-H Br contacts (C23-H23 Br 2.97 A, C25-H25 Br 2.99 A) result-
ing in a distorted octahedral arrangement around the Br atom and
thereby creating a three-dimensional network. C-H N and C-H Br
. . .
. . .
˚
. . .
˚
interactions with a mean bond distance of 2.64 A (CH ◦ N) and 2.75 A
. . .
. . .
(CH Br), respectively, and C-H X angles above 140 have been dis-
cussed in recent publications.29
The α-hydroxyphosphine oxide 3 crystallizes in P21/c and has one
molecule in the asymmetric unit. The coordination around phosphorous
is tetrahedral (Figure 3) with O-P-C angles that are slightly larger
than the C-P-C angles (Table II). Bond distances and angles com-
pare well to those of (2-Py)3PO30 or the related α-hydroxyphosphine

1408
R. J. Bowen et al.
FIGURE 1 Molecular structure of [(2-Py)3PEt]Br 1a. Thermal ellipsoids are
drawn on the 50% probability level. H atoms have been drawn at an arbitrary
radius.
oxides PhP(O)(CH2PH)C(Me)(Ph)OH,31 PhP(O)(Et)C(Me)(Ph)OH,32
Ph2P(O)C(OH)Me2,33 and PhPa(O)C(Me)(CH2)2CbH2(Pa-Cb).34 The
phosphorous atom of 3 is chiral (c.f., the two methyl groups are in-
equivalent in the 1H-NMR spectrum), and the two enantiomers form a
◦
˚
TABLE II Selected Bond Distances (A) and Angles ( ) for 1a and 3
[(2-Py)3PEt]Br 1a
(2-Py)P(O)(CH2Ph)CH(OH)Me2 3
P-Xa
P-C11
1.791 (2)
1.805 (2)
1.487 (1)
1.817 (2)
P-C21
1.810 (2)
1.812 (2)
P-C31
1.807 (2)
1.853 (2)
X-P-C11
X-P-C21
X-P-C31
C11-P-C21
C11-P-C31
C21-P-C31
111.55 (9)
108.68 (9)
109.33 (9)
107.17 (9)
109.88 (8)
110.20 (8)
110.81 (7)
113.34 (7)
111.50 (7)
105.11 (7)
109.01 (7)
106.76 (7)
aX = C1 (compound 1a), O1 (compound 3).

Alkyltris(2-Pyridyl)phosphonium Salts
1409
◦
˚
TABLE III Intermolecular Parameters (A, ) for
Compound 1a
. . .
. . .
. . .
. . .
D-H
A
D-H
H
A
D
A
D-H
A
a
. . .
C1-H1B N32
. . .
0.99
0.95
0.99
0.95
0.95
0.95
0.95
0.95
2.51
2.55
2.73
2.88
2.86
2.84
2.99
2.97
3.380 (2)
3.368 (3)
3.593 (2)
3.704 (2)
3.782 (2)
3.787 (2)
3.756 (2)
3.707 (2)
146
b
C26-H26 N12
144
146
146
163
174
139
135
. . .
C1-H1A Br
c
. . .
C14-H14 Br
d
. . .
C15-H15 Br
. . .
C16-H16 Br
e
. . .
C23-H23 Br
f
. . .
C25-H25 Br
Symmetry codes: (a) 1 − x, 1 − y, −z; (b) −x, 1 − y, −z; (c)
−1 + x, y, z; (d) 1 − x, −y, 1 − z; (e) 1 − x, −y, −z; (f) −1 + x,
y, −1 + z.
centrosymmetric, racemic dimer via hydrogen bonds (graph set R22(10))
between the oxygen atom O1 of the phosphine oxide and the hydroxy
functionality (Figure 4, Table IV), resulting in a molecular conforma-
tion where O1 and O2 are pointing approximately in the same direc-
tion [torsion angle O1-P-C31-O2 69.8(1)◦]. This is the first example
of such a structural motif in α-hydroxyphosphine oxides. Previously,
FIGURE 2 Intermolecular contacts in [(2-Py)3PEt]Br 1a.

1410
R. J. Bowen et al.
FIGURE 3 Molecular structure of (2-Py)P(O)(CH2Ph)C(OH)Me2 3. Thermal
ellipsoids are drawn on the 50% probability level. H atoms (except CH2 and
OH) have been omitted for clarity.
only H-bonding resulting in infinite linear chains with O-P-C-O tor-
sion angles in the range of 175 to 180◦ was observed for this class of
compounds.
EXPERIMENTAL
Synthesis
Solvents were used directly as purchased from Sigma Aldrich and not
dried. Deuterated solvents were degassed by freeze-drying and kept un-
der argon and molecular sieves. NMR spectra were recorded in CDCl3
◦
˚
TABLE IV H-bonding (A, ) in compound 3
. . .
. . .
. . .
. . .
A
D-H
A
D-H
0.84
H
A
D
A
D-H
163
a
. . .
O2-H2 O1
1.89
2.703(2)
Symmetry code: (a) −x, −y + 1, −z + 1.

Alkyltris(2-Pyridyl)phosphonium Salts
1411
FIGURE 4 H-bonded dimer of (2-Py)P(O)(CH2Ph)C(OH)Me2 3.
at 298 K using the following Bruker instruments: AVANCE 300 (1H,
300.13 MHz; 13C, 75.5 MHz; 31P 121.5 MHz), AVANCE DRX 400 (1H,
400.13 MHz; 13C, 100.6 MHz; 31P, 161.9 MHz) and referenced internally
to residual solvent resonances (data in δ) in the case of 1H and 13C spec-
tra. The 31P spectra were referenced externally to 85% H3PO4. All NMR
1
spectra other than H were proton decoupled. Hydrogen atoms in the
pyridyl rings were labelled according to their respective position in the
1
ring for an assignment of H-NMR spectra. The first order analysis
was used to assign the spectra. Melting points were recorded in un-
sealed capillaries and are uncorrected. Elemental analysis (empirical
formulae shown) was determined by the Institute for Soil, Climate and
Water, Pretoria, South Africa. The following abbreviations were used

1412
R. J. Bowen et al.
throughout the experimental section: d = doublet, m = multiplet, q =
quartet, s = singlet, and t = triplet. Coupling constants (J) are given
in Hz.
Ethyltris(2-Pyridyl)phosphonium Bromide 1a
Ethyl bromide (10 mL, 133.98 mmol) was added to tris(2-pyridyl)-
phosphine (0.50 g, 1.88 mmol). The mixture was refluxed at 40◦C for 70
h. The excess ethyl bromide was removed in vacuo, and a white solid
was obtained. The compound was recrystallized from methanol/ether
at −20◦C to give colorless crystals (0.32 g, 48%). m.p. (dec.): 177–178◦C.
Found: C, 55.7; N, 11.4; H, 4.8%; calc. for C17H17BrN3P: C, 54.6; N, 11.2;
H, 4.6%. 1H NMR (CDCl3, 300.13 MHz): δ 1.35 (m, CH3), 3.56 [overlap-
ping qd, CH2, 2 J(HP) 14.3 Hz, 3 J(HH) 7.5 Hz], 7.68 (m, H5-py, 3H),
8.08 (m, H4-py, 3H), 8.23 (m, H3-py, 3H) and 8.83 [d, H6-py, 3H, 4 J(HP)
4.6 Hz]. 31P NMR (CDCl3, 161.9 MHz): δ 15.4. 13C NMR (CDCl3, 75.5
MHz): δ 6.2 [d, CH3, 2 J(CP) 5.7 Hz], 14.8 [d, CH2, 1 J(CP) 50.7 Hz], 128.2
[d, p-py, 4 J(CP) 3.6 Hz], 132.3 [d, o-py, 2 J(CP) 22.7 Hz], 138.1 [d, m-py,
3 J(CP) 9.8 Hz], 142.8 [d, ipso-C, 1 J(CP) 115.0 Hz] and 151.6 [d, CN,
3 J(CP) 19.8 Hz].
Propyltris(2-Pyridyl)phosphonium Bromide 1b
Propyl bromide (10 mL, 110.08 mmol) was added to tris(2-pyridyl)-
phosphine (0.50 g, 1.88 mmol). The mixture was refluxed at 70◦C for
8 h. The excess propyl bromide was removed in vacuo, and a white solid
was obtained. The compound was recrystallized from acetone/hexane
at −20◦C to give white needle-shaped crystals (0.42 g, 58%). m.p. (dec.):
59–61◦C. 1H NMR (CDCl3, 400.13 MHz): δ 1.15 (m, CH3), 1.78 (m,
CH2), 3.62 (m, CH2), 7.67 (m, H5-py, 3H), 8.12 (m, H4-py, 3H), 8.42 (m-
4
H3, py, 3H) and 8.86 [d, H6-py, 3H, J(HP) 4.7 Hz]. 31P NMR (CDCl3,
161.9 MHz): δ 13.2. 13C NMR (CDCl3, 75.5 MHz): δ 14.7 [d, CH2, 2 J(CP)
3
1
16.9 Hz], 15.3 [d, CH3, J(CP) 4.6 Hz], 21.8 [d, CH2, J(CP) 48.9 Hz],
127.9 [d, p-py, 4 J(CP) 3.6 Hz], 131.6 [d, o-py, 2 J(CP) 22.6 Hz], 137.7 [d,
m-py, J(CP) 9.9 Hz], 142.4 [d, ipso-C, J(CP) 114.9 Hz] and 151.3 [d,
CN, 3 J(CP) 19.7 Hz].
3
1
Butyltris(2-Pyridyl)phosphonium Bromide 1c
Butyl bromide (10 mL, 93.12 mmol) was added to tris(2-pyridyl)-
phosphine (0.50 g, 1.88 mmol). The mixture was refluxed at 100◦C for
1.5 h. The excess butyl bromide was removed in vacuo, and a sticky

Alkyltris(2-Pyridyl)phosphonium Salts
1413
brown solid was obtained. The compound was recrystallized from ace-
tone/hexane at −20◦C to yield yellow crystals (0.25 g, 33%). m.p. (dec.):
101–103◦C. Found: C, 55.0; N, 10.0; H, 5.3%; calc. for C19H21BrN3P: C,
1
55.5; N, 10.2; H, 5.4%. H NMR (CDCl3, 400.13 MHz): δ 0.84 [t, CH3,
3 J(HH) 7.2 Hz], 1.50 (m, CH2), 1.62 (m, CH2), 3.62 (m, CH2), 7.57 (m,
H5-py, 3H), 8.02 (m, H4-py, 3H), 8.25 (m, H3-py, 3H) and 8.75 [d, H6-py,
3H, 4 J(HP) 4.6 Hz]. 31P NMR (CDCl3, 161.9 MHz): δ 13.5. 13C NMR
(CDCl3, 75.5 MHz): δ 13.2 (s, CH3), 20.2 [d, CH2, 1 J(CP) 49.4 Hz], 23.6
2
4
[d, CH2, J(CP) 12.0 Hz], 23.7 (s, CH2), 128.2 [d, p-py, J(CP) 3.5 Hz],
132.2 [d, o-py, 2 J(CP) 22.7 Hz], 138.1 [d, m-py, 3 J(CP) 9.8 Hz], 142.9 [d,
ipso-C, 1 J(CP) 115.0 Hz] and 151.7 [d, CN, 3 J(CP) 19.8 Hz].
Benzyltris(2-Pyridyl)phosphonium Bromide 1d (c.f. [16])
Benzyl bromide (5 mL, 42.03 mmol) was added to tris(2-pyridyl)-
phosphine (0.42 g, 1.58 mmol). The mixture was refluxed at 140◦C
for 3 h. The excess benzyl bromide was removed in vacuo to yield a
yellow solid. The compound was recrystallized from methanol/ether
at −20◦C to give yellow crystals (0.60 g, 87%). m.p. (dec.): 163◦C.
Found: C, 60.1; N, 9.4; H, 4.4%; calc. for C22H19BrN3P(H2O)1/2 (based
1
1
on the H-NMR spectrum 1d crystallizes with /2 equivalent of H2O):
C, 60.6; N, 9.6; H, 4.4%. 1H NMR (CDCl3, 300.13 MHz): δ 5.16 [d,
CH2, 2 J(HP) 15.5 Hz], 7.07–7.13 (multiple multiplets, Ph, 5H), 7.64
(m, H5-py, 3H), 8.03 (m, H4-py, 3H), 8.33 (m, H3-py, 3H) and 8.80 [d,
H6-py, 3H, 4 J(HP) 4.0 Hz]. 31P NMR (CDCl3, 161.9 MHz): δ 11.8. 13C
NMR (CDCl3, 75.5 MHz): δ 27.7 [d, CH2, 1 J(CP) 45.9 Hz], 126.7 [d,
o-Ph, 3 J(CP) 8.2 Hz], 127.4 [d, ipso-C, Ph, 2 J(CP) 69.7 Hz], 128.2 [d,
m-Ph, 4 J(CP) 3.6 Hz], 128.7 [d, p-Ph, 5 J(CP) 3.3 Hz], 130.5 [d, p-py,
2
3
4 J(CP) 5.8 Hz], 133.1 [d, o-py, J(CP) 22.6 Hz], 138.0 [d, m-py, J(CP)
9.9 Hz], 142.8 [d, ipso-C, py, 1 J(CP) 115.2 Hz] and 151.4 [d, CN, 3 J(CP)
20.1 Hz].
Benzyltris(2-Pyridyl)phosphonium Chloride 1e
Benzyl chloride (10 mL, 86.89 mmol) was added to tris(2-pyridyl)-
phosphine (0.42 g, 1.58 mmol). The mixture was refluxed at 120◦C for
6 h. The excess benzyl chloride was removed in vacuo, and a yellow
solid was obtained. The compound was triturated with acetone to give a
fine pale yellow powder (0.45 g, 62%). m.p. (dec.): 107–108◦C. 1H NMR
(CDCl3, 300.13 MHz): δ 5.28 [d, CH2, 2 J(HP) 15.5 Hz], 6.99 (broad s,
4
Ph, 5H), 7.60 (broad s, H5-py, 3H), 8.01 (d, H4-py, 3H, J(HP) 5.8 Hz),
3
4
8.42 [d, H3-py, 3H, J(HP) 5.7 Hz], 8.76 [d, H6-py, J(HP) 3.5 Hz]. 31P
NMR (CDCl3, 161.9 MHz): δ 12.0. 13C NMR (CDCl3, 100.6 MHz): δ 27.5

1414
R. J. Bowen et al.
[d, CH2, 1 J(CP) 45.0 Hz], 126.9 [d, o-Ph, 3 J(CP) 8.3 Hz], 128.4 [ipso-
2
C, Ph, J(CP) 53.4 Hz], 128.7 (s, m-Ph), 129.2 (s, p-Ph), 130.6 [d, p-py,
2
3
4 J(CP) 5.8 Hz], 133.1 [d, o-py, J(CP) 22.6 Hz], 138.0 [d, m-py, J(CP)
9.9 Hz], 143.1 [d, ipso-C, py, 1 J(CP) 115.2 Hz] and 151.3 [d, CN, 3 J(CP)
20.0 Hz].
2,2ꢀ-Bipyridinium(+1) Bromide 2
Butyltris(2-pyridyl)phosphonium bromide 1c was dissolved in hot ace-
tone/hexane to yield yellow crystals at −20◦C (0.27 g, 56%). m.p. (dec.):
1
75◦C. H NMR (CDCl3, 400.13 MHz): δ 7.79 [d, py-H, 3 J(HH) 0.8 Hz,
1H], 7.80–7.83 (m, py, 3H), 8.31–8.35 (m, py, 3H), 8.93 [d, py-H, 3 J(HH)
8.1 Hz, 1H) and 9.04 [dd, N-H, py, 4 J(HH) 0.8 Hz, 3 J(HH) 5.2 Hz, 1H].
13C NMR (CDCl3, 100.6 MHz): δ 124.4 (s, p-py), 126.5 (s, o-py), 142.2 (s,
m-py), 146.4 (ipso-C) and 148.0 (s, CN).
Compound 3
Benzyltris(2-pyridyl)phosphonium chloride 1e was dissolved in hot ace-
tone/hexane to yield yellow crystals (0.12 g, 29%) at 0◦C. 1H NMR
(CDCl3, 400.13 MHz): δ 1.41 [d, CH3, 3H, 3 J(HP) 13.1 Hz], 1.61 [d,
3
2
CH3, 3H, J(HP) 13.6 Hz], 3.51 [dd, CH2, 1H, J(HH) 14.4 Hz,2 J(HP)
16.9 Hz], 3.75 [dd, CH2, 1H, 2 J(HP) 9.2 Hz, 1H, 2 J(HH) 14.4 Hz], OH not
observed, 7.00–7.03 (multiple multiplets, Ph, 5H), 7.13–7.14 (multiple
multiplets, py, 1H), 7.41–7.70 (multiple multiplets, py, 2H) and 8.70 [d,
py-H, (1H), J(HP) 4.8 Hz]. 31P NMR (CDCl3, 161.9 MHz): δ 39.0. 13C
2
NMR (CDCl3, 100.6 MHz): δ 23.4 [d, CH3, 2 J(CP) 2.8 Hz], 25.6 [d, CH3,
2 J(CP) 8.5 Hz], 31.5 [d, CH2, 1 J(CP) 58.4 Hz], 71.7 [d, C-OH, 1 J(CP)
76.0 Hz], 125.6 [d, Ph, J(CP) 2.9 Hz], 126.4 [d, Ph, J(CP) 2.9 Hz], 128.2
[d, Ph, J(CP) 2.3 Hz], 129.8 [d, p-py, 4 J(CP) 4.7 Hz], 131.4 [d, o-py,
2 J(CP) 8.6 Hz], 136.7 [d, m-py, 3 J(CP) 7.8 Hz], 148.5 [d, CN, py, 3 J(CP)
15.4 Hz] and 155.6 [d, ipso-C (py), 1 J(CP) 106.5 Hz]; ipso-C, Ph not
observed.
Tris(2-Pyridyl)phosphine Oxide
Bromobenzene (10 mL, 86.89 mmol) was added to tris(2-pyridyl)-
phosphine (0.42 g, 1.56 mmol). The mixture was refluxed at 120◦C
for 8 days. The excess bromobenzene was removed in vacuo, and a
yellow solid was obtained. Colorless crystals (0.20 g, 38%) were ob-
tained from methanol at −60◦C. m.p.: 200◦C. Found: C, 64.5; N, 14.9; H,
4.4%; calc. for C15H12N3PO: C, 64.1; N, 14.9; H, 4.3%. 1H NMR (CDCl3,

Alkyltris(2-Pyridyl)phosphonium Salts
1415
300.13 MHz): δ 7.38 (m, H5-py, 3H), 7.81 (m, H4-py, 3H), 8.20 (m,
H3-py, 3H) and 8.78 [d, H6-py, 4 J(HP) 4.5 Hz]. 31P NMR (CDCl3,
161.9 MHz): δ 14.8. 13C NMR (CDCl3, 75.5 MHz): δ 125.5 [d, p-py,
2
3
4 J(CP) 3.3 Hz], 128.8 [d, o-py, J(CP) 21.2 Hz], 135.9 [d, m-py, J(CP)
9.5 Hz], 150.4 [d, CN, 3 J(CP) 19.3 Hz] and 154.7 [d, ipso-C, 1 J(CP)
133.1 Hz].
TABLE V Crystal Data and Refinement for Compounds 1a and 3
Compound
1a
3
Empirical formula
M
C17H17BrN3P
374.22
C15H18NO2P
275.27
T(K)
Wavelength (A)
Crystal system
173 (2)
0.71073
293 (2)
˚
0.71073
Monoclinic
P21/c
8.4196 (9)
17.2945 (19)
10.3595 (11)
90
106.796 (2)
90
1444.1 (3)
4
Triclinic
¯
Space group
P1
˚
a (A)
9.442 (1)
9.549 (1)
10.776 (1)
94.523 (2)
114.379 (2)
97.412 (2)
868.1 (2)
2
˚
b (A)
˚
c (A)
α (◦)
β (◦)
γ (◦)
3
˚
U (A )
Z
D (calc.) Mg/m3
1.432
2.459
1.266
0.188
µ (mm−1
)
F (000)
380
584
Crystal size (mm3)
Theta range for data
collection (◦)
0.37 × 0.36 × 0.11
0.33 × 0.28 × 0.15
2.10 to 28.27
2.36 to 28.31
Index ranges
−12 < = h< = 9
−12 < = k< = 12
−14 < = l < = 13
5926
−11 < = h< = 11
−23 < = k< = 17
−13 < = l < = 13
9601
Reflections collected
Independent reflections
Completeness to theta
Absorption correction
Max. and min. transmission
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices
4191 [R(int) = 0.017]
3568 [R(int) = 0.028]
97.0
99.3
Semi-empirical from equivalents None
0.7736 and 0.4631
4191/0/200
1.043
R1 = 0.028
0.9724 and 0.9406
3568/0/178
1.043
R1 = 0.038
[I > 2sigma(I)]
wR2 = 0.068
R1 = 0.035
wR2 = 0.095
R1 = 0.063
R indices (all data)
wR2 = 0.072
0.474 and −0.375
wR2 = 0.105
0.187 and −0.294
Large−s3t diff. peak and hole
˚
(eA
)

1416
R. J. Bowen et al.
Crystallography
Intensity data for crystal structures were collected on a Bruker
SMART 1K CCD area detector diffractometer with graphite
monochromated Mo Kα radiation (50 kV, 30 mA). The collection method
involved ω-scans of width 0.3◦. Data reduction was carried out using
35
the program SAINT+ and the data was processed further with the
program SADABS.35b Structures were solved by direct methods using
SHELXTL.36 Non-hydrogen atoms were first refined isotropically fol-
lowed by anisotropic refinement by full matrix least-squares calcula-
tions based on F2 using SHELXTL. Hydrogen atoms (except H2 of 3)
were located from the difference map and then positioned geometrically
and allowed to ride on their respective parent atoms. H2 was located
from the difference map and allowed to refine freely. Further crystal-
lographic data are summarized in Table V. Diagrams and publication
material were generated using SHELXTL,36 and PLATON,37 ORTEP,37
and SCHAKAL.38
Full crystallographic data (CCDC No. 267675 for compound 1a and
267676 for compound 3) have been deposited at the Cambridge Crystal-
lographic Database Centre and are available on request from the Direc-
tor, CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK (Fax: +44-1223-
336-033; E-mail:deposit@ccdc.cam.ac.uk or http://www.ccdc.cam.ac.uk).
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