Reaction of red phosphorus with 4-methoxystyrene in KOH-DMSO system: One-pot synthesis of tris[2-(4-methoxyphenyl)ethyl]phosphane oxide

Article abstract of DOI:10.1080/10426507.2010.482546

Red phosphorus reacts with 4-methoxystyrene in the KOH-DMSO superbase system (130 °C, 3 h, Ar) in the presence of a small quantity of H ₂O to give tris[2-(4-methoxyphenyl)ethyl]phosphane oxide as the main product in 30% yield. Microwave activation of the reaction (600 W, 6 min) affords basically a mixture of the phosphane oxide and tris[2-(4-methoxyphenyl) ethyl]phosphane (in a ratio of 1:1). When the mixture is exposed to air (r.t., 24 h), the phosphane oxide is formed in 85% yield. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.482546

Phosphorus, Sulfur, and Silicon, 186:98–104, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.482546
REACTION OF RED PHOSPHORUS
WITH 4-METHOXYSTYRENE IN KOH-DMSO SYSTEM:
ONE-POT SYNTHESIS OF TRIS[2-(4-METHOXYPHENYL)
ETHYL]PHOSPHANE OXIDE
Nina K. Gusarova, Svetlana F. Malysheva,
Natal’ya A. Belogorlova, Alexander V. Artem’ev,
Vladimir A. Kuimov, and Boris A. Trofimov
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian
Academy of Sciences, Irkutsk, Russia
GRAPHICAL ABSTRACT
Pred
+
OMe
OMe
MeO
KOH/DMSO(H2O)
P
o
130 C, 3 h
30%
85%
O
or
MW, 6 min
OMe
Abstract Red phosphorus reacts with 4-methoxystyrene in the KOH-DMSO superbase sys-
tem (130 ◦C, 3 h, Ar) in the presence of a small quantity of H2O to give tris[2-(4-
methoxyphenyl)ethyl]phosphane oxide as the main product in 30% yield. Microwave activation
of the reaction (600 W, 6 min) affords basically a mixture of the phosphane oxide and tris[2-
(4-methoxyphenyl)ethyl]phosphane (in a ratio of 1:1). When the mixture is exposed to air (r.t.,
24 h), the phosphane oxide is formed in 85% yield.
Keywords 4-Methoxystyrene; microwave irradiation; phosphane oxide; red phosphorus; su-
perbase system
INTRODUCTION
One-pot phosphorylation of available electrophiles (e.g., aryl- and hetarylalkenes,
acetylenes, organic halides, alkene oxides) with red phosphorus in combination with
Received 4 March 2010; accepted 30 March 2010.
Financial support from the Russian Foundation for Basic Research (grant no. 08-03-00251) is gratefully
acknowledged.
Address correspondence to Nina K. Gusarova, A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch
of the Russian Academy of Sciences, 1 Favorsky Street, 664033, Irkutsk, Russia. E-mail: gusarova@irioch.irk.ru
98

RED PHOSPHORUS WITH 4-METHOXYSTYRENE
99
superbase systems such as KOH–nonhydroxylic polar solvent (DMSO, HMPA)–H2O rep-
resents one of the most convenient and promising approaches to the C P bond formation
and synthesis of fundamental organophosphorus compounds, in particular, phosphanes,
phosphane oxides, and phosphinic acids.1 The key steps of these phosphorylations include
likely the cleavage of P P bonds in the macromolecule of red phosphorus (probably oc-
curring in phosphorus nanoparticles) by hydroxide anions to form highly active P-centered
nucleophiles such as polyphosphide A and polyphosphinite B anions and their further
interaction with an electrophile1c (Scheme 1).
OH
Pred
P
+
P
OH
A
OH
- H2O
P
P
OH
O
B
Scheme 1
The essence of these reactions is a competition between the polyphosphide and
polyphosphinite anions for the electrophile. For example, red phosphorus reacts with
weak electrophilic alkenes such as styrene2 and 4-(tert-butyl)styrene3 in the KOH-
DMSO system under an argon blanket to deliver tris(2-phenylethyl)- and tris[4-(tert-
butylphenyl)ethyl]phosphane oxides (but not the corresponding phosphanes). Therefore,
in these processes, polyphosphinite anions B win the competition over polyphosphide
anions A (Scheme 2).
R
R
R
KOH/DMSO(H2O)
Ar
Pred
P
P
O
O
B
R = H (58%), tBu (77%)
R
Scheme 2
In these cases, DMSO does not act as an oxidizer, since under the conditions studied,
phosphane, which is easily generated from red phosphorus in KOH/H2O/toluene (or diox-
ane) medium,4,5 is added to styrene4,6 and 4-(tert-butyl)styrene5 in a KOH/DMSO system
to give the corresponding secondary or tertiary phosphanes.
At the same time, the literature is lacking data on the interaction of phosphorus-
centered nucleophiles with alkoxyvinylarenes. The realization of such reactions is prob-
lematic, because the presence of an electron-donating methoxy group in the 2- or 4-positions
of the benzene ring of alkoxyvinylbenzenes decreases electrophilicity of the double bond

100
N. K. GUSAROVA ET AL.
of these alkenes and, therefore, their reactivity towards nucleophiles. For example, 4-
methoxystyrene reacts with such nucleophiles as BuLi, tert-BuLi,7 or PhCH2NH2 and
8
Me2CHCN9 in the presence of superbase systems more slowly and under harsher condi-
tions than styrene.
In this article, based on the example of 4-methoxystyrene, we report for the first time
the addition of phosphorus-centered nucleophiles generated from red phosphorus in the
superbase system to the double bond of alkoxyvinylarenes.
RESULTS AND DISCUSSION
We have found that 4-methoxystyrene (1) reacts with red phosphorus in the KOH-
DMSO suspension in the presence of small quantity of H2O (as a proton donor) and hydro-
quinone as a radical process inhibitor at 130 ◦C for 3 h under an argon blanket to give tris[2-
(4-methoxyphenyl)ethyl]phosphane oxide (2) and 2-(4-methoxyphenyl)ethylphosphinic
acid (3) in 30% and 10% yields, respectively (Scheme 3).
MeO
OMe
OMe
HO
O
KOH/DMSO(H2O)
Ar, 130 oC, 3 h
Pred
+
P
P
+
O
H
OMe
OMe
3 (10%)
1
2 (30%)
Scheme 3
Styrene turns out to be more reactive in this reaction. The phosphorylation of
styrene with red phosphorus in the system КОН-DMSO(H2O) proceeds at 120◦C for
3 h to furnish tris(2-phenylethyl)phosphane oxide, bis(2-phenylethyl)phosphinic, and 2-
phenylethylphosphinic acids in up to 64% total yield. The yield of the main product,
tris(2-phenylethyl)phosphane oxide, is 59%.
Microwave-assisted reaction of red phosphorus with 4-мethoxystyrene not only short-
ens the process duration (by approx. 20 times), but noticeably affects on its chemoselectivity.
Thus, a microwave irradiation (600 W, 6 min) promoted version of the reaction (with the
same reactants ratio) delivers, along with the anticipated phosphane oxide 2, the corre-
sponding tertiary phosphane 4 in 88% total yield, the ratio of the products being 1:1 (31Р
NMR). In addition, the reaction gives bis[2-(4-methoxyphenyl)ethyl]phosphinic acid (5) in
small yield (7%) (Scheme 4).
The mixture of compounds 2 and 4 was exposed to air (r.t., 24 h) to afford phosphane
oxide 2 in 85% isolated yield.
The formation of phosphane 4 in the phosphorylation of styrene 1 with red phosphorus
in the KOH-DMSO system likely occurs via polyphosphide anions (A) (Scheme 5).
Accordingly, phosphane oxide 2 and phosphinic acids 3 and 5 in the reactions studied
are formed apparently with the participation of polyphosphinite anions (B) (Scheme 6).
In conclusion, the results obtained contribute fundamentally to phosphorus and ary-
lalkenes chemistry, as well as allow the novel tertiary phosphane oxide 2 to be synthesized
in up to 85% yield. Microwave-assisted reaction of red phosphorus with 4-methoxystyrene

RED PHOSPHORUS WITH 4-METHOXYSTYRENE
101
OMe
OMe
HO
O
KOH/DMSO(H2O)
MW, Ar
2
P
Pred
+
P
+
+
OMe
MeO
OMe
OMe
4
5 (7%)
1
Scheme 4
MeO
1/
OH/ H2O
1/
OH/ H2O
1/H2O
4
P
P
P
A
MeO
Scheme 5
OMe
MeO
MeO
MeO
OH/1/H2O
OH/1/H2O
1/H2O
P
P
P
2
O
O
O
B
OH/H2O
OH/H2O
5
3
Scheme 6
affects the chemoselectivity of the process and increases its rate. This approach opens a
straightforward route to phosphane oxide, and hence, the corresponding phosphane bears
electron-rich alkoxyaryl substituents. Such types of phosphorus compounds are of special
importance and are used as ligands for the design of new catalytic systems for cross-
coupling reactions,10 the C H bond activation reactions,11 ester hydrogenation,12 addition
of arylboronic acids to aldehydes,13 cyanosilylation and cyanocarbonation of carbonyl
compounds,14 and aminocarbonylation of alkyl iodides.15
EXPERIMENTAL
IR spectra were measured with a Bruker IFS 25 instrument in microlayer or KBr
(cm−1). 1H, 13C, and 31P NMR spectra were recorded on a Bruker DPX-400 spectrometer
(at 400.13, 100.61, and 161.98 MHz, respectively) in CDCl3 solutions and referenced to
internal HMDS (1H), CHCl3 (13C) and external 85% H3PO4 (31P). Two-dimensional homo-
and heteronuclear NMR correlation experiments (NOESY, HSQC) were used to assign the
signals in 1Н and 13C NMR spectra. Microwave irradiation was performed in multimode,

102
N. K. GUSAROVA ET AL.
modified microwave oven, Samsung M181DNR (max. power level 850 W) equipped with
a reflux condenser. We used an open vessel microwave technology (atmospheric pressure).
The reaction of red phosphorus with styrene was performed in a round bottom flask (Pyrex).
A 500 mL one-necked flask was placed into the multimode reactor [impulse magnetron
OM75P(31), power 1.25 MW/2.45 GHz] and was equipped with a reflux condenser, which
was brought out via a special hole. Red phosphorus from KSAN “SIA” was employed. 4-
Methoxystyrene was synthesized according to the literature.16 All reactions were conducted
under an argon atmosphere.
Synthesis of Tertiary Phosphine Oxide 2
A mixture of red phosphorus (11 mmol), styrene 1 (13.3 mmol), KOH·0.5H2O (13
mmol), water (0.07 mL), DMSO (15 mL), and hydroquinone (0.01 g) was stirred for 3
◦
h at 130 C, diluted with water (25 mL), and extracted with CHCl3 (3 × 20 mL). The
chloroform extract was washed with a 20% aq solution of KCl (3 × 15 mL) and dried
over K2CO3. The solvent and unreacted 4-methoxystyrene (1.02 g, 43% conversion) were
removed under reduced pressure. The residue was washed with hexane (3 mL) and dried in
vacuum to furnish 0.27 g (30%) phosphane oxide 2. The aqueous layer was acidified with
a 35% aq НCl up to рН 4–5 (to neutralize 4-MeOC6H4CH2CH2PH(O)OK) and extracted
with chloroform (3 × 20 mL). The chloroform extract was washed with water (3 × 15 mL)
and dried over CaCl2. Then the solvent was removed, and the residue was dried in vacuum
to give 0.11 g (10%) of phosphinic acid 3.
Tris[2-(4-methoxyphenyl)ethyl]phosphane oxide 2. Colorless powder, 1.04
g (85%) yield, mp 129–131◦C (hexane). 1H NMR (CDCl3), δ (ppm), J (Hz): 1.92–2.00 (m,
6H, CH2P), 2.79–2.86 (m, 6H, CH2C6H4), 3.76 (m, 9H, ОMe), 6.86–7.06, and 7.06–7.08
(m, 12H, C6H4); 13C NMR (CDCl3), δ (ppm), J (Hz): 26.91 (CH2C6H4), 31.40 (d, 1JPC
61.5 Hz, CH2P), 55.28 (Me), 114.10 (C-oC6H4), 129.02 (C-mC6H4), 132.75 (d, JPC
=
3
=
12.4 Hz, C-iC6H4), 158.56 (C-pC6H4); 31P NMR (CDCl3), δ (ppm): 47.01. IR (KBr), ν,
cm−1: 3058, 3016, 2955, 2932, 2908, 2870, 2836, 1610, 1583, 1512, 1461, 1440, 1301,
1273, 1180, 1161, 1129, 1099, 1033, 948, 851, 832, 817, 788, 751, 722, 661, 637, 541,
525, 469. Anal. Calcd for C27H33O4P: C, 71.66; H, 7.35; P, 6.84. Found: C, 71.57; H, 7.33;
P, 6.70.
2-(4-Methoxyphenyl)ethylphosphinic acid 3. Colorless crystalline powder,
0.11 g (10%) yield, mp 229–232◦C (ethanol). 1H NMR (D2O), δ (ppm), J (Hz): 1.80–1.88
1
(m, 2Н, CH2P), 2.75–2.82 (m, 2H, CH2C6H4), 3.83 (s, 3H, OMe), 6.94 (d, 1H, JPH
=
505.7 Hz, PH), 6.94 and 7.48 (m, 4Н, C6H4), 8.02 (br. s, 1H, OH); 13C NMR (CDCl3), δ
(ppm), J (Hz): 25.94 (CH2C6H4), 32.72 (d, 1JPC = 94.2 Hz, CH2P), 54.95 (OMe), 113.80
(C-оC6H4), 129.01 (C-mC6H4), 134.27 (C-iC6H4), 147.61 (C-pC6H4); 31P NMR (D2O), δ
1
(ppm), J (Hz): 30.18 (d, JPH = 505.8 Hz); IR (KBr), ν, cm−1: 3436, 2956, 2935, 2837,
2295, 2100, 2600, 1629, 1613, 1585, 1514, 1465, 1443, 1421, 1302, 1250, 1210, 1176,
1129, 1057, 1036, 938, 919, 903, 847, 817, 783, 736, 637, 620, 581, 549, 520, 490, 474,
442. Anal. Calcd for C9H13O3P: C, 54.00; H, 6.55; P, 15.47. Found: C, 54.27; H, 6.73; P,
15.76.
Phosphorylation of 4-Methoxystyrene with Red Phosphorus
Under Microwave Irradiation
A mixture of red phosphorus (11 mmol), styrene 1 (13.3 mmol), hydroquinone
(0.01 g), КОН·0.5H2O (13 mmol), water (0.07 mL), and DMSO (15 mL) was irradiated in

RED PHOSPHORUS WITH 4-METHOXYSTYRENE
103
microwave oven (600 W) at 180◦C for 6 min (real time of magnetron action was 3 min). The
reaction mixture was cooled and analyzed by 31Р NMR. The mixture contained phosphine
oxide 2 (47.01 ppm) and phosphine 4 (–28.13 ppm) in the ratio of 1:1. The mixture was
exposed to air for 24 h, diluted with water (25 mL). Unreacted phosphorus was filtered
off and washed with water (30 mL) up to neutral pH, and dried on air to recover 0.104 g
of red phosphorus (conversion 69%). The filtrate was extracted with CHCl3 (3 × 25 mL),
then the chloroform extract was washed with a 20% aq solution of KCl (3 × 10 mL) and
dried over K2CO3. The solvent and unreacted 4-methoxystyrene (0.82 g, 64% conversion)
were removed under reduced pressure. The residue (1.1 g) was precipitated from CHCl3 (5
mL) with hexane (40 mL), and the precipitate was dried in vacuum to give 1.04 g (85%) of
phosphine oxide 2. The aqueous layer was acidified with a 35% aq НCl up to рН 4–5 (to
neutralize (4-MeOC6H4CH2CH2)2P(O)OK) and extracted with chloroform (3 × 20 mL).
The chloroform extract was washed with water (3 × 15 mL) and dried over CaCl2. Then the
solvent was removed, and the residue was dried in vacuum to give 0.1 g (7%) of phosphinic
acid 5.
Bis[2-(4-methoxyphenyl)ethyl]phosphinic acid 5. Colorless crystalline pow-
der, 0.1 g (7%) yield, mp 237–241◦C (ethanol). 1H NMR (D2O), δ (ppm), J (Hz): 1.50–1.70
(m, 4Н, CH2P), 2.50–2.72 (m, 4H, CH2C6H4), 3.69 (s, 6H, OMe), 6.83 and 7.08 (m, 8Н,
C6H4), 7.87 (br. s, OH); 13C NMR (D2O), δ (ppm), J (Hz): 27.64 (CH2C6H4), 31.68 (d,
1JPC = 80.1 Hz, CH2P), 55.43 (OMe), 114.02 (C-оC6H4), 129.36 (C-mC6H4), 135.34 (d,
3JPC = 14 Hz, C-iC6H4), 157.15 (C-pC6H4); 31P NMR (D2O), δ (ppm), J (Hz): δ 44.73; IR
(KBr), ν, cm−1: 3440, 2956, 2937, 2856, 2838, 2600, 2200, 1632, 1614, 1585, 1556, 1514,
1465, 1454, 1417, 1405, 1335, 1303, 1249, 1215, 1178, 1135, 1120, 1099, 1035, 938, 872,
853, 824, 785, 753, 699, 667, 636, 618, 558, 444. Anal. Calcd for C18H23O4P: C, 64.66; H,
6.93; P, 9.26. Found C, 64.57; H, 6.85; P, 9.47.
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