Synthesis of diphenyl(nitroaryl)phosphine oxides via oxidative nucleophilic substitution of hydrogen in nitroarenes with diphenylphosphine anion

Article abstract of DOI:10.1055/s-0028-1087354

Potassium and sodium salts of diphenylphosphine add to nitroarenes in the position ortho and para to the nitro group. Subsequent oxidation of σ^H-adducts with potassium permanganate gave diphenyl(nitroaryl)phosphine oxides. Georg Thieme Verlag S

Full text of DOI:10.1055/s-0028-1087354

2938
LETTER
Synthesis of Diphenyl(nitroaryl)phosphine Oxides via Oxidative Nucleophilic
Substitution of Hydrogen in Nitroarenes with Diphenylphosphine Anion
Synthesis of
D
iphenyl(
i
nitroar
e
yl)phosphin
c
e
Oxide
s
v
z
ia
O
N
SH R
y
eaction sław Mąkosza,* Maciej Paszewski, Daniel Sulikowski
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax +48(22)6326681; E-mail: icho-s@icho.edu.pl
Received 4 September 2008
ammination agent of highly electron-deficient heteroare-
Abstract: Potassium and sodium salts of diphenylphosphine add to
nitroarenes in the position ortho and para to the nitro group. Subse-
quent oxidation of sH-adducts with potassium permanganate gave
diphenyl(nitroaryl)phosphine oxides.
nes, oxidative variant of the Chichibabin reaction.10b
Since liquid ammonia is an excellent solvent for genera-
tion and reactions of carbanions, we have used this system
for ONSH in nitroarenes with variety of carbanions.10 The
reaction proceeds satisfactorily with carbanions of high
nucleophilicity; hence sH-adducts thus formed are rela-
tively stable and can be subsequently oxidized.
Key words: phosphine oxides, nucleophilic aromatic substitution,
nitroarenes, carbanions
Taking into account the high nucleophilicity of diphe-
nylphoshine anion we expected that it should add to ni-
troarenes in positions ortho and para to the nitro group
giving sH-adducts and that addition should proceed com-
pletely. Subsequent oxidation of these sH-adducts should
give diphenyl(nitroaryl)phosphines or phosphine oxides,
products of the ONSH reaction.
Organophosphorus compounds have found wide applica-
tion as intermediates and reagents in organic synthesis.1
For instance, phosphines are key reagents in important
processes such as Mitsunobu,2,3 Wittig,3,4 Appel,3,5
Staudinger3,6 and many other reactions. Phosphines are in-
dispensable ligands for transition metal catalysts that pro-
mote a great variety of reactions.7 Due to this, a variety of
methods for the synthesis of substituted phosphines and
phosphinoxides have been developed.1,8
Indeed, addition of commercially available THF solution
of potassium salt of diphenylphosphine anion 1 to a solu-
tion of nitrobenzene 2 in liquid ammonia and treatment of
the resulting mixture after 15 minutes with potassium per-
manganate gave the expected diphenyl(nitrophenyl)phos-
phine oxide as a mixture of ortho- (2a) and para- (2b)
isomers in a total yield of almost 60% (Scheme 1,
Table 1). According to our previous observations,12d the
use of two equivalents of KMnO4 should assure complete
oxidation of sH-adduct and phosphine. Thus, after addi-
tion of the diphenylphosphine anion to nitrobenzene, two
oxidation processes proceeded consecutively, oxidation
of the sH-adducts to the corresponding nitrophenyl diphe-
nylphosphines and subsequent oxidation of the phos-
phines to phosphinoxides. One cannot exclude a priori an
alternative pathway, oxidation of the trivalent phospho-
rous in the sH-adduct to produce sH-adduct of diphe-
nylphosphinoxides followed by oxidation of the latter.
In spite of the great interest in synthesis of phosphines and
phosphinoxides, those containing nitroaryl substituents
are almost unknown. We have found very few papers re-
porting synthesis of diphenyl(nitrophenyl)phosphines and
their oxides. The reaction of alkyl diphenylphosphinite
with o-dinitrobenzene gave diphenyl-o-nitrophenylphos-
phinoxide in a kind of aromatic Michaelis–Becker reac-
tion.9 An alternative approach is direct or electrochemical
nitration of triphenylphosphine, which gives products of
mono- and dinitration.10
In this letter we report that diphenyl-[o(p)-nitroaryl]phos-
phinoxides can be synthesized via oxidative nucleophilic
substitution of hydrogen (ONSH) in nitroarenes with an-
ion of diphenylphosphine.
Oxidative nucleophilic substitution of hydrogen in ni-
troarenes and other electron-deficient arenes is presently a
well-developed method for introduction of nitrogen, oxy-
gen and carbon substituents into electron-deficient aro-
matic rings.11,12a The reaction proceeds via addition of
respective nucleophiles: ammonia,12b hydroxyl anion,12c
carbanions12d–12g or Grignard reagents12h,i to nitroaromatic
rings in positions occupied by hydrogen followed by oxi-
dation of the produced sH-adducts with external oxidants.
For ONSH a variety of solvent–oxidant systems can be
used.13 Particularly efficient is a solution of potassium
permanganate in liquid ammonia that serves as efficient
To clarify this point we have oxidized the sH-adduct of
diphenylphosphine with an insufficient quantity of potas-
sium permanganate and obtained a mixture of the corre-
sponding phosphine and phosphinoxide. This result
suggest that oxidation of the sH-adducts to diphenyl(ni-
troaryl)phosphines is the initial process.
Under identical conditions other nitroarenes reacted with
1 producing the expected diphenyl(nitroaryl)phosphine
oxides (Scheme 1, Table 1).14,15
The reaction of nitrobenzene and ortho and meta substi-
tuted nitrobenzenes with potassium diphenylphosphide
always gave mixtures of p- and o-nitroaryldiphenylphos-
phinoxides that were very difficult to separate by conven-
SYNLETT 2008, No. 19, pp 2938–2940
x
x
.x
x
.2
0
0
8
Advanced online publication: 12.11.2008
DOI: 10.1055/s-0028-1087354; Art ID: G29806ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Diphenyl(nitroaryl)phosphine Oxides via ONSH Reaction
2939
It is known that diphenylphosphine salts can be obtained
by direct cleavage of triphenylphosphine with lithium, so-
dium or potassium.16 We have therefore attempted to per-
form one-pot reaction starting with Ph3P. Treatment of
triphenylphosphine with sodium in liquid ammonia gave
a dark solution containing undoubtedly sodium salt of
diphenylphosphine that upon addition of an excess of ni-
trobenzene followed by oxidation with potassium per-
manganate gave the expected product, a mixture of 2a and
2b in 45% yield (Scheme 2).17
Z
NO2
–
–
NO2
NO2
H
2–10
liq NH3
PPh2
Z
Z
H
PPh2
Ph2P–K+
1
KMnO4
NO2
NO2
NO2
O
NO2
NO2
NO2
PPh2
PPh2
1)
KMnO4
Na
Ph2P–Na+
Ph3P
+
+
Z
Z
liq NH3
2) KMnO4
liq NH3
Z
PPh2
Z
PPh2
PPh2
O
O
2a–10a
2a, 2b
2b–10b
Scheme 2
Scheme 1 Reaction of potassium diphenylphosphide with nitroar-
enes.
In this communication we have presented a new method
for the synthesis of diphenyl(nitroaryl)phosphine oxides
utilizing oxidative nucleophilic substitution of hydrogen
in nitroarenes with diphenylphosphine salts, that could be
extended on other electron-deficient arenes.
Table 1 Results of ONSH in Nitroarenes with Diphenylphosphine
Anion
Entry Nitroarenes
Z
Products
Regioisomer Overall
ratioa
yield (%)
References and Notes
1
2
3
4
5
6
7
8
9
H
2
3
2a/2b
3a/3b
4a/4b
5a/5b
6b
87:13
83:17
91:9
58
60
33
70
37
54
35
41
41
(1) (a) Quin, L. D. A Guide to Organophosphorus Chemistry;
John Wiley & Sons: New York, 2000. (b) The Chemistry of
Organophosphorus Compounds; Hartley, F. R., Ed.; Vol. 1,
John Wiley & Sons: New York, 1992. (c) The Chemistry of
Organophosphorus Compounds; Hartley, F. R., Ed.; Vol. 2,
John Wiley & Sons: New York, 1992.
2-Cl
2-Br
3-Cl
3-Br
3-F
4
5
80:20
100:0
6
(2) (a) Mitsunobu, O. Synthesis 1981, 1. (b) Mitsunobu, O.
Org. React. (N. Y.) 1992, 42, 335.
(3) Cadogan, J. I. G. Organophosphorus Reagents in Organic
Chemistry; Academic Press: London, 1979.
(4) (a) Hoffmann, R. W. Angew. Chem. Int. Ed. 2001, 40, 1411.
(b) Johnson, A. W. Ylides and Imines of Phosphorus; John
Wiley & Sons: New York, 1993.
(5) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
(6) Staudinger, H.; Meyer, J. Helv. Chim. Acta 1919, 2, 635.
(7) Borner, A. Phosphorus Ligands in Asymmetric Catalysis;
Wiley-VCH: Weinheim, 2008.
(8) (a) Sasse, K. In Houben–Weil, Vol. 12/1; Müller, E., Ed.;
Thieme: Stuttgart, 1963, 17–65, 135–168. (b) Engel, R.
Synthesis of Carbon–Phosphorus Bonds; CRC Press: Boca
Raton, 1988. (c) Pietrusiewicz, K. M.; Zabłocka, M. Chem.
Rev. 1994, 94, 1375. (d) Helmchen, G. In Houben–Weil,
Vol. E21e; Mikołajczyk, M.; Drabowicz, J.; Kiełbasiński,
P., Ed.; Thieme: Stuttgart, 1995, 5701–5732.
7
7a1/7a2/7b 58:33:9
4-Cl
4-F
8
8a
0:100
0:100
94:6
9
9a
1-NNb
10
10a/10b
a Isomer ratio (para/ortho) was determined using 31P NMR spectros-
copy.
b 1-NN: 1-nitronaphthalene.
tional chromatographic techniques. Attempts to change
solvents, temperature and oxidants resulted in lower
yields of the nitroarylated phosphines and did not affect
regioselectivity of the reaction.
(9) Cadogan, J. I. G.; Sears, D. J.; Smith, D. M. J. Chem. Soc. C
1969, 1314.
On the other hand, the reaction of p-fluoro- and p-chloro-
nitrobenzene with 1 gave exclusively single products of
the ONSH, diphenyl(o-nitroaryl)phosphine oxides. It
should be stressed that even when p-fluoronitrobenzene
was used in this reaction, we did not find in the reaction
mixture diphenyl(p-nitrophenyl)phosphine oxide, product
of SNAr of fluorine.
(10) (a) Maccarone, E.; Passerini, A.; Passerini, R.; Tassone, G.
Gazz. Chim. Ital. 1989, 119, 545. (b) Fagdar-Cosma, G.;
Fagdar-Cosma, E.; Taranu, I. Rev. Roum. Chim. 2005, 291.
(11) (a) Chupakin, O. N.; Charushin, V. N.; Van der Plas, H. C.
Nucleophilic Aromatic Substitution of Hydrogen; Academic
Press: San Diego, 1994. (b) Terrier, F. Nucleophilic
Aromatic Displacement: The Influence of the Nitro Group.
Synlett 2008, No. 19, 2938–2940 © Thieme Stuttgart · New York

2940
M. Mąkosza et al.
LETTER
Organic Nitro Chemistry Series; Wiley: New York, 1991.
(c) Mąkosza, M.; Paszewski, M. Pol. J. Chem. 2005, 79,
163.
isomer): d = 149.9 (d, J = 3 Hz), 140.3 (d, J = 98 Hz), 133.2
(d, J = 11 Hz), 132.6 (d, J = 3 Hz), 132.0 (d, J = 10 Hz), 128.8
(d, J = 12 Hz), 128.6, 123.3 (d, J = 12 Hz). 31P NMR (162
MHz, CDCl3): d = 27.70 (s, para isomer), 28.39 (s, ortho
isomer). MS (EI, 70 eV): m/z (%) = 323 (48) [M+], 322
(100), 277 (26), 201 (12), 77 (13).
(12) (a) Mąkosza, M.; Staliński, K. Pol. J. Chem. 1999, 73, 151.
(b) Van der Plas, H.; Woźniak, M. Croat. Chim. Acta 1986,
59, 33. (c) Kolesnichenko, G. A.; Malyklin, E. V.;
Shteingarts, V. D. Zh. Obshch. Khim. 1986, 22, 806.
(d) Makosza, M.; Staliński, K. Chem. Eur. J. 1997, 3, 2025.
(e) Mąkosza, M.; Kamieńska-Trela, K.; Paszewski, M.;
Bechcicka, M. Tetrahedron 2005, 61, 11952. (f) Mąkosza,
M.; Surowiec, M.; Szczepanska, A.; Sulikowski, D.;
Maltsev, O. Synlett 2007, 470. (g) Florio, S.; Mąkosza, M.;
Lorusso, P.; Troisi, L. Arkivoc 2006, (vi), 59. (h) Bartoli, G.
Acc. Chem. Res. 1984, 17, 109. (i) Mąkosza, M.; Surowiec,
M. J. Organomet. Chem. 2001, 624, 167.
(13) (a) Kienzle, F. Helv. Chim. Acta 1978, 61, 449. (b) Bartoli,
G.; Bosco, M. Synthesis 1980, 616. (c) Bartoli, G.; Bosco,
M.; Dalpozzo, R.; Todesco, P. E. J. Org. Chem. 1986, 56,
3694. (d) Nilson, M.; Ullenius, C.; Wennerstrom, O.
Tetrahedron Lett. 1971, 29, 2713. (e) Fukazawa, Y.;
Kurata, Y.; Saito, N.; Takeda, Y.; Usui, S. J. Org. Chem.
1989, 54, 2982.
(14) Representative Procedure: To a stirred solution of
nitrobenzene (246 mg, 2.00 mmol) in liquid ammonia (ca.
10 mL), at –78 °C was added dropwise a solution of
diphenylphosphine potassium salt (0.5 M solution in THF,
2.0 mL, 1.0 mmol). After 15 min, solid potassium
permanganate (396 mg, 2.00 mmol) was added. The dark
mixture was stirred for further 5 min, and treated with excess
of solid ammonium chloride. After evaporation of ammonia
the residue was suspended in EtOAc (20 mL), stirred for 10
min and filtered through a small pad of celite. The organic
phase was washed once with H2O, dried with anhyd Na2SO4
and evaporated. Column chromatography on silica gel
(EtOAc) gave a mixture of o- and p-nitrophenyl
Compound 6b: 159–161 °C (heptane). 1H NMR (400 MHz,
CDCl3): d = 8.50 (m, 1 H), 8.18 (ddd, J = 8.6, 2.1, 1.4 Hz,
1 H), 7.69–7.77 (m, 4 H), 7.60–7.76 (m, 3 H), 7.45–7.59 (m,
4 H). 31P NMR (162 MHz, CDCl3): d = 29.59 (s). MS (EI, 70
eV): m/z (%) = 402 (100)[M+], 356 (20), 322 (22), 201 (43),
77 (23).
Compound 8a: mp 210–211 °C (MeOH). 1H NMR (400
MHz, CDCl3): d = 8.07–8.11 (m, 2 H), 7.63–7.80 (m, 5 H),
7.54–7.62 (m, 2 H), 7.33–7.53 (m, 4 H). 13C NMR (100
MHz, CDCl3): d = 149.2, 140.5 (d, J = 13 Hz), 136.3 (d,
J = 7.5 Hz), 133.0 (d, J = 2.1 Hz), 132.3 (d, J = 2.5 Hz), 131.6
(d, J = 10 Hz), 131.5, 128.6 (d, J = 13 Hz), 126.5 (d, J = 5
Hz). 31P NMR (162 MHz, CDCl3): d = 29.50 (s). MS (ESI+):
m/z = 358 [M + H]+.
Compound 9a: mp 162–163 °C (MeOH). 1H NMR (400
MHz, CDCl3): d = 8.12–8.30 (m, 1 H), 7.63–7.81 (m, 5 H),
7.55–7.62 (m, 3 H), 7.36–7.53 (m, 4 H). 13C NMR (100
MHz, CDCl3): d = 132.6 (d, J = 3 Hz), 132.2, 131.9 (d,
J = 10 Hz), 130.2, 129.0 (d, J = 13 Hz), 128.5 (d, J = 9 Hz),
128.4 (d, J = 9 Hz), 124.1 (dd, J = 8, 26 Hz), 120.3 (m), 120.0
(m). 31P NMR (162 MHz, CDCl3): d = 30.01 (s). MS (ESI+):
m/z = 342 [M + H]+.
(16) (a) Kashibawara, K.; Jung, M.; Fujita, J. Bull. Chem. Soc.
Jpn. 1991, 64, 2373. (b) Al-Benna, S.; Sarsifield, M. J.;
Thornton-Pett, M.; Ormsby, D. L.; Maddox, P. J.; Bres, P.;
Bochmann, M. J. Chem. Soc., Dalton Trans. 2000, 23, 4247.
(17) One-Pot Procedure: To a suspension of triphenylphosphine
(262 mg, 1.00 mmol) in liquid ammonia at –78 °C, sodium
metal was added (26 mg, 1.10 mmol). The resulting mixture
was stirred for 1 h and to the dark red solution nitrobenzene
(369 mg, 3.00 mmol) in THF (1 mL) was added. After 15
min the mixture was treated with solid KMnO4, and after 5
min solid ammonium chloride was added. Workup as in ref.
14 gave a mixture of 2a and 2b (138 mg, 45% yield).
diphenylphosphinoxide (178 mg, 58% yield) as an oil.
(15) Selected analytical data:
Mixture 2a/2b: light orange oil. 1H NMR (400 MHz, CDCl3;
para isomer): d = 8.30 (dd, J = 2.1, 8.8 Hz, 2 H), 7.89 (dd,
J = 11.0, 8.8 Hz, 2 H), 7.63–7.74 (m, 4H), 7.55–7.63 (m,
2H), 7.46–7.55 (m, 4 H). 13C NMR (100 MHz, CDCl3; para
Synlett 2008, No. 19, 2938–2940 © Thieme Stuttgart · New York