The reaction of 2-bromopyridine with a PH3/H2 system in the KOH/DMSO suspension: A short route to tris(2-pyridyl)phosphine

Article abstract of DOI:10.1002/hc.21030

The straightforward reaction of 2-bromopyridine with a PH ₃/H₂ system (generated from phosphorus red and aqueous alkali) in the superbasic KOH/DMSO/(H₂O) suspension under mild conditions (70°C, 1.5 h, atmospheric pressure) affords selectively and cleanly tris(2-pyridyl)phosphine in 50% yield; no admixtures of the expected primary and secondary pyridylphosphines were observed in the crude product.

Full text of DOI:10.1002/hc.21030

Heteroatom Chemistry
Volume 00, Number 0, 2012
T
he Reaction of 2-Bromopyridine with a
PH /H System in the KOH/DMSO Suspension:
3
2
A Short Route to Tris(2-pyridyl)phosphine
Boris A. Trofimov, Nina K. Gusarova, Alexander V. Artem’ev,
Svetlana F. Malysheva, Nataliya A. Belogorlova, and Anastasiya
O. Korocheva
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of
Sciences, 1 Favorsky Str., 664033 Irkutsk, Russian Federation
Received 18 January 2012; revised 14 May 2012
intermediates for syntheses of heteroatom and inor-
ABSTRACT: The straightforward reaction of 2-
ganic compounds [5] and medicine precursors [6].
bromopyridine with a PH
3
/H system (generated from
2
Among pyridylphosphines, (2-pyridyl)phosphines,
in particular, tertiary tris(2-pyridyl)phosphine, are
of special interest due to the geminal disposition of
such chemically and biologically important donor
heteroatoms as nitrogen and phosphorus [7], which
secures the cooperative chelating interaction with
different electron-deficient substrates [3]. Diverse
ligations of tris(2-pyridyl)phosphine led to numer-
ous novel and useful complexes [3,8], some of which
were explored as catalysts for such industrially
meaningful reactions as methoxycarbonylation of
alkynes [9], hydroformylation of alkenes [10], ethy-
lene polymerization [11], and Diels–Alder synthesis
phosphorus red and aqueous alkali) in the superbasic
KOH/DMSO/(H
2
O) suspension under mild conditions
◦
(70 C, 1.5 h, atmospheric pressure) affords selectively
and cleanly tris(2-pyridyl)phosphine in 50% yield; no
admixtures of the expected primary and secondary
pyridylphosphines were observed in the crude product.
ꢀ
2
C
2012 Wiley Periodicals, Inc. Heteroatom Chem 00:1–4,
012; View this article online at wileyonlinelibrary.com.
DOI 10.1002/hc.21030
INTRODUCTION
[
12].
Pyridylphosphines are widely used for the synthe-
sis of transition metal organic compounds [1] with
unusual coordination properties and catalytic ac-
tivity [2]. The affinity of such ligands toward cat-
alytically active transition metals makes them ideal
tools for constructing heteroatomic architectures
Pyridylphosphines are usually synthesized from
pyridyl metal derivatives (Li, Mg) and phosphorus
halides [3]. These syntheses require low temperature
(
mosphere to avoid isomerization and deterioration
of intermediates. For the isolation of the products
◦
−110 C for lithium derivatives [13]) and inert at-
[3]. Tris(pyridyl)phosphines were shown to be re-
(yields about 45%), laborious column chromatog-
warding building blocks for the diverse supramolec-
ular structures [4]. Besides, they were reported to be
raphy procedures are necessary [13]. Recently [14],
tris(2-pyridyl)- and tris(3-pyridyl)phosphines were
prepared in 70–75% yields via the Grignard route
◦
(
dry THF, −78 C). In the latter case, the target phos-
Correspondence to: B. A. Trofimov; e-mail: boris trofimov@
irioch.irk.ru.
Contract grant sponsor: Russian Foundation for Basic
Research.
phines were isolated by tedious extraction of the re-
sulting solid with a large amount of diethylamine,
because the Mg cations strongly increased the sol-
ubility of these phosphines in aqueous media [14].
2+
Contract grant number: 11-03-00286.
ꢀ
c 2012 Wiley Periodicals, Inc.
1

2
Trofimov et al.
H
P
PH /H2
N
Br
N
Br
3
N
Br KOH/DMSO/(H
O),
KOH/DMSO/(H O)
KOH/DMSO/(H O)
N
2
PH2
2
N
2
N
o
7
0 C, 1.5 h
A
B
not observed
not observed
3
1
31
(
P NMR)
(
P NMR)
N
N
N
P
1, 50%
SCHEME 1 Synthesis of tris(2-pyridyl)phosphine from 2-bromopyridine and phosphine.
–
Br
OH
N
OH
N
Br
1
H
N
P
H
N
N
P
N
–
–Br
PH
H
2
O
P
–Br
H
2
O
N
2
N
A
C
B
D
SCHEME 2 Plausible mechanism of 2-bromopyridine phosphination.
RESULTS AND DISCUSSION
matic substitution of the bromine atom in the 2-
bromopyridine ring with participation of all bulkier
phosphide-anions C and D (ionized phosphines A
and B) (Scheme 2).
Moreover, the repulsive interaction between
phosphorus-centered anions C, D, and nitrogen lone
electron pairs should additionally interfere with
the direct nucleophilic substitution. Apparently, all
these negative effects are excessively compensated
by the higher concentration of the intermediate an-
ions C and D. The latter is an expected result of the
augmented acidity of phosphines A and B.
In this article, we describe for the first time
a new simple and efficient synthesis of tris(2-
pyridyl)phosphine by the straightforward reaction
of 2-bromopyridine with a PH
3
/H mixture. The
2
process proceeds smoothly under mild conditions
◦
(
70 C, atmospheric pressure), when the PH
3
/H mix-
2
ture (∼1:1) is passed through (45–50 bubbles per
min) the superbasic suspension KOH/DMSO/(H O),
-bromopyridine gradually (1.5 h) being dropped to
2
2
the reaction medium (Scheme 1). The yield (not op-
timized) of tris(2-pyridyl)phosphine (1) is 50%. The
An alternative to this mechanism may be the
elimination–addition scheme (via dehydropyridine),
although the 100% regioselectivity of the reaction
seems to be not in keeping with this assumption.
Another alternative could involve the nucleophilic
substitution of bromine by hydroxide anion and a
further reaction of the 2-hyrdoxypyridine 2-pyridone
mixture with phosphines. However, these special
mechanistic issues are the subject of our further in-
vestigation.
PH
3
/H reagent is readily generated at the controlled
2
rate by slow addition of aqueous KOH (50%) to the
phosphorus red/toluene suspension at 75–80 C ac-
◦
cording to the protocol [15]. Here, the hydrogen
gas is likely to protect (against oxidation) the P(III)
species in the reaction process. The synthesis is fairly
selective and clean: Only tris(2-pyridyl)phosphine is
formed, and no admixtures of the expected primary
(
A) and secondary (B) phosphines as well as any po-
sition isomers are observed in the reaction mixture
Scheme 1).
Indeed, our failure to detect ( P NMR) inter-
(
31
CONCLUSION
mediates A and B in the resulting crude prod-
uct seems surprising, because every next step to-
ward the synthesis of final tris(2-pyridyl)phosphine
should be more sterically hindered as the formal aro-
In conclusion,
a one-pot synthesis of tris(2-
pyridyl)phosphine in 50% yield by the straightfor-
ward reaction of available 2-bromopyridine with the
Heteroatom Chemistry DOI 10.1002/hc

Reaction of 2-Bromopyridine with a PH /H System in the KOH/DMSO Suspension
3
3
2
PH
3
/H
2
system in the superbasic KOH/DMSO/(H
2
O)
dried in vacuo (1 Torr) to give pure phosphine 1
as microcrystalline powder. Yield: 2.8 g (50%), mp
◦
suspension under mild conditions (70 C, 1.5 h, at-
mospheric pressure) has been developed. The con-
trolled PH
◦
◦
115–116 C (i-PrOH), lit. 113 C [13]. IR (KBr): 3039,
2961, 2900, 1572, 1558, 1450, 1424, 1413, 1283,
1276, 1147, 1085, 1045, 987, 960, 907, 896, 774,
765, 743, 721, 712, 618, 548, 513, 503, 496, 426,
3
/H gas flow has been safely generated
2
by dosed addition of aqueous KOH to red phos-
phorus in toluene. An advantageous feature of the
synthesis is its high selectivity: No correspond-
ing primary and secondary phosphines as well as
their position isomers have been detected in the
crude reaction mixture. This new simple access
to tris(2-pyridyl)phosphine substantially expands its
application as a powerful tripodal ligand for de-
sign of metal complex catalysts and novel het-
eroatomic supramolecular architectures, potent syn-
thetic building block, and drug precursor.
−
1
1
407, 395 cm . H NMR (400.13 MHz, CDCl ): δ
3
3
= 7.18–7.23 (m, 3H, H-5), 7.41 (d, JHH = 7.0 Hz,
3
3H, H-3), 7.58–7.64 (m, 3H, H-4), 8.72 (d,
J
HH
=
13
3.70 Hz, H-6). C NMR (100.62 MHz, CDCl
3
): δ =
CP = 19.3 Hz, C-2), 135.6
CP = 2.6 Hz, C-4), 150.1 (d, CP = 19.3 Hz,
C-3), 161.5 (C-6). P NMR (161.98 MHz, CDCl ):
δ = −0.06. Anal. Calcd for C15 P: C, 67.92; H,
4.56; N, 15.84; p, 11.68. Found: C, 67.85; H, 4.41; N,
5.74; p, 11.50.
1
122.5 (C-5), 128.9 (d,
J
3
2
(d,
J
J
31
3
H
12
N
3
1
EXPERIMENTAL
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Heteroatom Chemistry DOI 10.1002/hc