Efficient One-Pot Synthesis of Mono- and Bis[di(2-pyridyl)phosphine Oxides] from Tris(2-pyridyl)phosphine

Article abstract of DOI:10.1055/s-0035-1562485

An efficient one-pot access to di(2-pyridyl)phosphine oxides Py₂P(R)=O and bis[di(2-pyridyl)phosphine oxides] Py₂P(O)-Z-P(O)Py has been developed based on the reaction of available tris(2-pyridyl)phosphine with various organic halides, followed by treatment of the resulting phosphonium salts with alkali in situ. The isolated yields of the phosphine oxides were in the range 40-96%.

Full text of DOI:10.1055/s-0035-1562485

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© Georg Thieme Verlag Stuttgart · New York
2016, 27, A–D
letter
A
S. F. Malysheva et al.
Letter
Synlett
Efficient One-Pot Synthesis of Mono- and Bis[di(2-pyridyl)phos-
phine Oxides] from Tris(2-pyridyl)phosphine
Svetlana F. Malysheva
Nina K. Gusarova
1) R-X
or
N
O
Ar(CH2Cl)2
N
N
R
P
Ar
or
Nataliya A. Belogorlova
Anastasiya O. Sutyrina
Yuriy I. Litvintsev
P
P
N
2) KOH
N
P
O
O
3
N
N
63–96%
40–96%
Alexander I. Albanov
Irina V. Sterkhova
Alexander V. Artem’ev*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch,
Russian Academy of Sciences, 1 Favorsky Str., 664033, Irkutsk,
Russian Federation
chemisufarm@yandex.ru
Received: 07.05.2016
Accepted after revision: 29.06.2016
Published online: 25.07.2016
terest as bridging ligands for the design of coordination
polymers.8 Py2P(Ph)=O is generally synthesized by H2O2 ox-
idation of the corresponding phosphine, which, in turn, is
generated by the reaction of either PhPCl2 with 2-pyridyl-
lithium at –90 °C (60% yield)9 or PhPLi2 with 2-chloropyri-
dine (83% yield).10 [(E)-alkenyl]bis(2-pyridyl)phosphine ox-
ides have recently been prepared in 45–56% yield by the re-
action of tris(2-pyridyl)phosphine with electron-deficient
alkynes in water.11
DOI: 10.1055/s-0035-1562485; Art ID: st-2016-b0324-l
Abstract An efficient one-pot access to di(2-pyridyl)phosphine oxides
Py2P(R)=O and bis[di(2-pyridyl)phosphine oxides] Py2P(O)–Z–P(O)Py2
has been developed based on the reaction of available tris(2-pyr-
idyl)phosphine with various organic halides, followed by treatment of
the resulting phosphonium salts with alkali in situ. The isolated yields of
the phosphine oxides were in the range 40–96%.
Here, we report an efficient one-pot synthesis of tertia-
ry bis(2-pyridyl)phosphine oxides and bis[di(2-pyr-
idyl)phosphine oxides] from the appropriate organic ha-
lides and tris(2-pyridyl)phosphine, which is now readily
available by the direct reaction of elemental phosphorus
with 2-bromopyridine.12
After a series of test experiments, we established that
the phosphonium salts 2a–g, prepared in situ by the reac-
tion of tris(2-pyridyl)phosphine (1) with organic halides
(1:10 molar ratio, 24–140 °C, 0.5–1.5 h, no solvent) reacted
readily with KOH (1:1.1 ratio, r.t., 0.5 h) to provide the cor-
responding bis(2-pyridyl)phosphine oxides 3a–f in 63–96%
preparative yield (Table 1).13 We also showed that the treat-
ment of the specially prepared intermediate phosphonium
salts 2a–g with alkali under similar conditions also led to
the phosphine oxides 3a–f in comparable yields (for details,
see the Supporting Information).14
The one-pot synthesis has a general character for organ-
ic chlorides, bromides, and iodides (Table 1) and permits
the synthesis of diverse bis(2-pyridyl)phosphine oxides
bearing alkyl (Table 1, entries 1–4) or benzylic substituents
(entries 5–7). Secondary and tertiary alkyl halides, e.g. i-PrI,
s-BuI, or t-BuBr, were ineffective in the reaction.
In the reaction of the phosphonium salts 2a–g with al-
kali (step ii), GC/MS analysis of the reaction mixture
showed that, in addition to potassium halides, pyridine and
2,2′-bipyridine were formed as byproducts of the reaction.
Key words dipyridylphosphine oxides, bisphosphine oxides, phospho-
nium salts, ligands, halo compounds, chemoselectivity
Pyridylphosphine oxides are currently attracting in-
creasing attention due to their importance in materials sci-
ence, catalysis, and coordination chemistry.1 Most studies
relate to tris(2-pyridyl)phosphine oxide, a useful ligand and
building block for functional materials.2 The closest ana-
logues of tris(2-pyridyl)phosphine oxide, the bis(2-pyr-
idyl)phosphine oxides Py2P(R)=O, have been much less ex-
plored, although they are of particular interest as intriguing
ligands for the assembly of unique metal complexes. For ex-
ample, Cu(I)3 and Ln(III)4 complexes based on bis(2-pyr-
idyl)phosphine oxides have been proposed as advanced
materials for light-emitting devices. In a series of works,5
Espinet and co-workers identified peculiarities in the dy-
namic behavior of Pd(II) and Pt(II) complexes of
Py2P(Ph)=O. Also, Rh(I)6 and Mo7 complexes that are cata-
lytically active in the hydrogenation of olefins were pre-
pared from this ligand.
The studies discussed above dealt only with phenyl-
bis(2-pyridyl)phosphine oxide; other bis(2-pyridyl)phos-
phine oxides Py2P(R)=O remain neglected because of their
unavailability. Bis[di(2-pyridyl)phosphine oxides] Py2P(O)–
Z–P(O)Py2 are virtually unknown, other than the com-
pound in which Z = (CH2)2,4a although they would be of in-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

B
S. F. Malysheva et al.
Letter
Synlett
Table 1 One-Pot Synthesis of Phosphine Oxides 3a–f from Tris(2-pyridyl)phosphinea
R
N
O
N
N
N
N
ii. KOH·0.5H2O
i. R-X
P
X
R
N
P
– K-X
– Py
P
N
N
3a–f (63–96%)
1
2a–g
Entry
Conditions for quaternization of phosphine 1 [step (i)]
Product
Yieldb (%)
RX
MeI
Temp (°C)
Time (h)
1
2
3
4
5
6
7c
24–25
45
0.5
0.5
1
3a
3b
3c
3d
3e
3e
3f
96
63
75
88
74
78
65
EtI
BuI
70
Me(CH2)8I
BnCl
140
140
140
140
1
1.5
1.5
1
BnBr
1-NaphCH2Cl
a Reaction conditions: i. phosphine 1 (0.5 mmol), RX (5.0 mmol), stirring, inert atmosphere; ii. KOH·0.5H2O (0.55 mmol), r.t., 0.5 h, stirring.
b Isolated yield.
c A 1:1 molar ratio of 1 to 1-(chloromethyl)naphthalene was used with DMF (3 mL) as solvent.
Interestingly, decompositions of similar salts in acetone in
the absence of alkali gave 2,2′-bipyridine hydrobromide,
along with PyP(R)(O)C(Me2)OH.15 Apparently, the forma-
tion of the phosphine oxides 3a–f occurs through nucleop-
hilic substitution of one of the pyridyl groups in the or-
ganyl[tris(2-pyridyl)]phosphonium cation by a hydroxide
anion. In all the above cases, the reaction is strictly chemo-
selective in terms of the leaving group on the phosphorus
atom in 2a–g: no alternative nucleophilic substitution of a
benzyl or 2-naphthylmethyl group (or of an alkyl group) by
HO– was observed. However, 9-fluorenyl, a better leaving
group, was replaced by the hydroxide anion more easily
than the 2-pyridyl unit. Thus, the phosphonium salt 2h,
prepared from phosphine 1 and 9-bromo-9H-fluorene (65%
yield), reacted with alkali in a 1:1.1 molar ratio to give
tris(2-pyridyl)phosphine oxide and 9H-fluorene in nearly
quantitative yield (Scheme 1).14 The expected (9H-fluoren-
9-yl)bis(2-pyridyl)phosphine oxide was not identified
among the reaction products.
To prepare the previously unknown bis[di(2-pyr-
idyl)phosphine oxides] 5, we extended the substrate scope
of our approach to organic dihalides (Table 2). The reaction
of tris(2-pyridyl)phosphine (1) with bis(chloromethyl)-
substituted aromatics (2:1 molar ratio, DMF, 150 °C, 1 h),
and subsequent treatment of the resulting bis(phosphoni-
um) salts 4a–d with KOH in situ (1:2.2 molar ratio, EtOH,
r.t., 0.5 h) gave the corresponding bis(phosphine oxides)
5a–d in moderate to high yields (Table 2, entries 1–4).14
DMF was used as a solvent because both reactants were sol-
ids. Bis(phosphine oxides) 5a–d are promising ligands for
the design of functional coordination polymers and supra-
molecular structures of a new generation. The intermediate
salts 4a–d were optionally isolated in 54–85% yield,14 with
the exception of 4b, which readily converted into 5b upon
handling.
N
Br
1
N
P
DMF, 150 °C, 1 h
N
Br
2h (65%)
N
KOH/EtOH
r.t., 0.5 h
O
+
P
N
N
91%
90%
Scheme 1 Synthesis of phosphonium salt 2h and its reaction with alkali
Figure 1 X-ray crystal structure of phosphine oxide 3e
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

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S. F. Malysheva et al.
Letter
Synlett
Table 2 One-Pot Synthesis of Bis(phosphine oxides) 5a–d from Tris(2-pyridyl)phosphine (1)a
Cl
Cl
N
N
i. Z(CH2Cl)2
P
1
Z
P
DMF, 150 °C,
1 h
N
N
N
N
4a–d
ii. KOH·0.5H2O
N
N
P
Z
P
EtOH, r.t., 0.5 h
O
O
N
N
5a–d (40–96%)
Entry
1
ClCH2–Z–CH2Cl
1,2-(ClCH2)2C6H4
Product
Yieldb (%)
40
N
N
N
N
P
P
O
O
(5a)
2
3
1,3-(ClCH2)2C6H4
75
96
N
N
N
P
P
N
O
O
O
(5b)
1,4-(ClCH2)2C6H4
N
P
N
O
N
N
P
(5c)
4
[4-(ClCH2)C6H4]2
67
N
O
P
N
N
N
P
O
(5d)
a Reaction conditions: i. phosphine 1 (0.5 mmol) , ClCH2–Z–CH2Cl (0.25 mmol), DMF (3 mL), 150 °C, 1 h, stirring; ii. KOH·0.5H2O (1.1 mmol), r.t., 0.5 h, stirring.
b Isolated yield.
The phosphine oxides 3a–f and 5a–d are air-stable crys-
tals or oils, readily soluble in common organic solvents and
almost insoluble in water. All the synthesized compounds
(including the intermediate phosphonium salts) were fully
characterized by NMR (1H, 13C, and 31P), Fourier-transform
IR spectroscopy, and elemental analysis. For compound 3e,
the structure was also determined by X-ray crystallography
(Figure 1).16
In summary, we have elaborated an efficient one-pot
access to di(2-pyridyl)phosphine oxides 3 and bis[di(2-pyr-
idyl)phosphine oxides] 5 from tris(2-pyridyl)phosphine,
which is now available.11 Quaternization of tris(2-pyr-
idyl)phosphine with organic mono- or dihalides and subse-
quent treatment of the resulting phosphonium salts with
alkali in situ gave the corresponding phosphine oxides in up
to 96% isolated yield. The products might be useful as li-
gands for the design of functional metal complexes, as po-
tential extractants for rare-earth metals, and as one-step
© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D

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S. F. Malysheva et al.
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Synlett
precursors to pyridylphosphines. We have synthesized a se-
ries of complexes {Cu2(μ-I)2(3a–f)} that exhibited a strong
yellow photoluminescence at room temperature (these re-
sults will be published elsewhere).
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Acknowledgment
The authors are grateful to the Baikal Analytical Center for the spec-
tral measurements.
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1562485.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
References and Notes
A mixture of tris(2-pyridyl)phosphine (1; 133 mg, 0.5 mmol)
and the appropriate organic halide (5.0 mmol) was stirred at
24–140 °C for 0.5–1.5 h (see Table 1). When the reaction was
complete (31P NMR), the mixture was cooled to 20–25 °C and
powdered KОН·0.5 H2O (36 mg, 0.55 mmol) was added. The
mixture was stirred for another 30 min at this temperature
until the 31P NMR resonance from the phosphonium salts 2a–g
disappeared. CHCl3 (5 mL) was then added to the resulting mix-
ture, the undissolved residue was removed by filtration, and the
filtrate was concentrated. The residue was mixed with anhyd
Et2O (3 mL) and the mixture was filtered. The volatiles were
evaporated from the filtrate and the residue was dried in vacuo
(1 Torr).
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Methylbis(2-pyridyl)phosphine Oxide (3a)
Yellow-brown oil; yield: 105 mg (96%). FT-IR (film): 3048, 2992,
2918, 2854, 1661, 1575, 1455, 1426, 1292, 1197, 1133, 1084,
1045, 990, 885, 761, 706, 618, 513 cm–1. 1H NMR (400.13 MHz,
CDCl3): δ = 2.20 (d, 2JPH = 13.6 Hz, 3 H, Me), 7.34–7.38 (m, 2 H, H-
3 in Py), 7.76–7.81 (m, 2 H, H-4 in Py), 8.04–8.07 (m, 2 H, H-5 in
Py), 8.77 (d, 3J6–5 = 4.5 Hz, 2 H, H-6 in Py). 13C NMR (100.62 MHz,
CDCl3): δ = 13.57 (d, 2JPC = 76.6 Hz, Me), 125.42 (d, 4JPC = 1.9 Hz
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2
3
C-5 in Py), 127.12 (d, JPC = 19.8 Hz, C-3 in Py), 136.11 (d, JPC
=
8.5 Hz, C-4 in Py), 150.33 (d, 3JPC = 19.1 Hz, C-6 in Py), 156.55 (d,
1JPC = 127.6 Hz, C-2 in Py). 31P NMR (161.98 MHz, CDCl3): δ =
32.28; Anal. Calcd for C11H11N2OP: С, 60.55; Н, 5.08; N, 12.84.
Found: С, 60.47; Н, 5.16; N, 12.65.
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© Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, A–D