Reaction of secondary phosphine oxides with aromatic aldehydes

Article abstract of DOI:10.1023/B:RUGC.0000015976.82173.42

Nucleophilic addition of secondary phosphine oxides to aromatic aldehydes proceeds under mild conditions (20-60°C, 10-40 h) and provides [bis(2-organylethyl)](arylhydroxymethyl)phosphine oxides in high yields.

Full text of DOI:10.1023/B:RUGC.0000015976.82173.42

Russian Journal of General Chemistry, Vol. 73, No. 9, 2003, pp. 1354 1357. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 9, 2003,
pp. 1433 1436.
Original Russian Text Copyright
2003 by Ivanova, Reutskaya, Gusarova, Medvedeva, Afonin, Ushakov, Tatarinova, Trofimov.
Reaction of Secondary Phosphine Oxides
with Aromatic Aldehydes
N. I. Ivanova, A. M. Reutskaya, N. K. Gusarova, S. A. Medvedeva,
A. V. Afonin, I. A. Ushakov, A. A. Tatarinova, and B. A. Trofimov
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences, Irkutsk, Russia
Received December 13, 2003
Abstract Nucleophilic addition of secondary phosphine oxides to aromatic aldehydes proceeds under mild
conditions (20 60 C, 10 40 h) and provides [bis(2-organylethyl)](arylhydroxymethyl)phosphine oxides in
high yields.
Secondary and tertiary phosphine oxides are readily
available by direct reactions of elemental phosphorus
with electrophilic agents in the presence of strong
bases [1 3]. In the course of systematic reactivity
studies on these compounds we showed that diorganyl-
phosphine oxides readily add to heteroaromatic al-
dehydes, namely, of the imidazole and benzamidazole
series, to give in high yields new functionally sub-
stituted tertiary phosphine oxides. The latter are
known as highly reactive building blocks and inter-
mediate products for designing biologically active
compounds and polydentate ligands for metal-
complex catalysts, as well as as promising objects for
basic research in the area of theoretical coordination
chemistry [4 7].
Aiming at gaining further information on the re-
gularities in reactions of secondary phosphine oxides
with aldehydes and preparing polyfunctional tertiary
phosphine oxides, in the present work we focused on
the reactions of the available bis(2-phenylethyl)- and
bis[2-(2-pyridyl)ethyl]phosphine oxides [2, 3, 8] with
aromatic aldehydes, such as benzaldehyde (IIa),
vanillin (IIb), and syringaldehyde (IIc).
The reaction of bis(2-phenylethyl)phosphine oxide
(I) with aldehydes IIa IIc proceeds under mild condi-
tions (20 60 C, dioxane, 10 40 h) and, with equi-
molar reactant amounts, gives phosphine oxides IIIa
IIIc in yields of 62 82%.
R1
R1
R2
H
O
O
R2
R3
(1)
C
+
P
P
O
H
CH
R3
OH
IIIa IIIc
I
IIa IIc
R1 = R2 = R3 = H (IIa, IIIa); R1 = H, R2 = OH, R3 = OMe (IIb, IIIb); R1 = R3 = OMe, R2 = (IIc, IIIc).
The highest yield (82%) at the lowest temperature
and reaction time (20 C, 10 h) was obtained with
benzaldehyde.
IIIb and IIIc are 62 and 64%, respectively. It should
be noted that under the above conditions the starting
bis(2-phenylethyl)phosphine oxide is concurrently
oxidized to bis(2-phenylethyl)phosphinic acid [9].
Reactions (1) with aldehydes IIb and IIc require
higher temperatures and/or more time to occur: 18 h
(20 60 C) and 40 h (20 ), respectively. Under these
conditions, the yields of tertiary phosphine oxides
Bis[2-(2-pyridyl)ethyl]phosphine oxide (IV) reacts
with benzaldehyde slightly slower (20 C, 18 h, me-
thanol) than phosphine oxide I, providing tertiary
phosphine oxide V in 73% yield.
1070-3632/03/7309-1354$25.00 2003 MAIK Nauka/Interperiodica

REACTION OF SECONDARY PHOSPHINE OXIDES
1355
rate of reaction (1) with aldehydes IIb and IIc can be
also associated with steric effects in intermediate A:
the stronger these effects, the less this intermediate
state is favored by energy and, therefore, the harder it
to form [10].
N
O
H
+ IIIa
P
P
N
N
The lower reactivity of phosphine oxide IV with
pyridine substituents as compared with phosphine
oxide I in the reaction with benzaldehyde can be ex-
plained by the fact that the electrophilic assistance of
the proton in the first case is suppressed by additional
and competing hydrogen bonding (intra- or intermole-
cular) with the highly basic pyridine nitrogen atom.
IV
V
O
(2)
CH
OH
N
Thus, the reaction of secondary phosphine oxides
with aromatic aldehydes is a convenient and efficient
synthetic route to new polyfunctional tertiary phos-
phine oxides.
1
The most characteristic signals in the H and 13C
NMR spectra of compounds IIIa IIIc and V are those
of the CH group in the fragment HOCHP=O:a doublet
at 5.0 5.1 ppm with the geminal coupling constant
31P H of 7 9 Hz (1H NMR) and a doublet near
EXPERIMENTAL
1
72 ppm (1JPC 60 Hz) (13C NMR). The observed non-
1
equivalence of signals of the two phenyethyl groups
The H and 13C NMR spectra were recorded on
in the H and 13C NMR spectra for phosphine oxides
Bruker DPX-400 and DPX-250 spectrometers for
CDCl3 and CD3OD solutions against internal HMDS.
1
IIIa IIIc is explained by the presence of a chiral
The 31P NMR spectra were obtained on a Bruker
DPX-400 spectrometer for the same solutions against
external 85% H3PO4. The structure of phosphine
oxides IIIa IIIc and V was confirmed by means of
1H and 31P NMR spectroscopy, and with compounds
IIIa IIIc, 1H 13C HSQC [11] and HMBC [12] correla-
tion techniques were applied.
carbon atom in the HOCHP=O fragment.
It can be inferred that reactions (1) and (2) proceed
via intermediate A and involve nucleophilic attack of
the three-coordinate phosphorus atom in the tauto-
meric forms of phosphine oxides I and IV on the
carbonyl carbon atom of aldehydes IIa IIc with elec-
trophilic assistance from the P OH proton of the
phosphine oxide.
[Bis(2-phenylethyl)](phenylhydroxymethyl)-
phosphine oxide (IIIa). A mixture of 0.24 g of bis-
(2-phenylethyl)phosphine oxide (I) and 0.11 g of al-
dehyde IIa in 2 ml of dioxane was stirred at room
temperature (24 25 C) for 10 h. Precipitate formation
was observed. The solvent was distilled off in a
vacuum, and the residue was washed with ether and
dried in a vacuum (1 2 mm) to obtain 0.31 g (82%)
H P
O
HO P
1
of phosphine oxide IIIa, mp 142 144 C (hexane). H
IIa IIc
NMR spectrum (CD3OD), , ppm: 7.55 m (2H, Hr,
PhCHOH), 7.43 m (2H, Hm, PhCHOH), 7.38 m (1H,
Hp, PhCHOH), 7.27 m (4H, Hm, PhCH2), 7.25 (2H,
Hr, PhCH2), 7.20 m (2H, Hp, PhCH2), 7.11 m (2H,
R1
+
:
P
>
+
R2
R3
O
<
O---H
2
Hr, PhCH2), 5.11 d (1H, CH, JPH 8.8 Hz), 4.80 br.s
(1H, HH), 2.95 m (2H, CH2Ph), 2.74 m (1H, CH2Ph),
2.53 m (1H, CH2Ph), 2.19 m (2H, CH2P), 1.96 m (2H,
CH2P). 13C NMR spectrum (CD3OD), C, ppm:
A
(3)
IIIa IIIc
3
142.68 d (2C, Ci, PhCH2, JPC 12.7 Hz), 138.71 s
Stability of this intermediate state depends on the
electron-acceptor power of the aryl substituent in the
aldehyde and should be decreased in the case of al-
dehydes IIb and IIc which have electron-donor sub-
stituents in their nuclei. This suggestion is consistent
with the observation of a higher reactivity of benzal-
dehyde in the reaction under study. The relatively low
(1C, Ci, PhCHOH), 129.66 s (2C, Cm, PhCH2),
129.61 s (2C, Cm, PhCH2), 129.42 s (2C, Cm,
PhCHOH), 129.25 s (2C, Co, PhCH2), 129.08 s (1C,
Cp, PhCHOH), 129.08 s (2C, Co, PhCH2), 127.82 s
(2C, Co, PhCHOH), 127.43 s (1C, Cp, PhCH2),
1
127.35 s (1C, Cp, PhCH2), 72.22 d (1C, CH, JPC
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 9 2003

1356
IVANOVA et al.
1
81.3 Hz), 28.64 d (1C, CH2P, JPC 60.6 Hz), 28.24 s
phenylethyl)phosphine oxide ( 31 ppm) and bis-
P
(1C, CH2Ph), 28.26 s (1C, CH2Ph), 26.88 d (1C,
(2-phenylethyl)phosphinic acid (
54.3 ppm, iden-
H
1
CH2P, 1JPC 60.6 Hz). 31P NMR spectrum (CDCl3):
tified with a reference sample) in a 65:35 ratio. H
NMR spectrum (CD3OD), , ppm: 7.28 m (4H, Hm,
Ph), 7.23 m (2H, Ho, Ph), 7.14 m (2H, Hp, Ph), 7.11
m (2H, Ho, Ph), 6.80 s [2H, H2 (H6)], 5.03 d (1H, CH,
2JPH 7.3 Hz), 4.80 br.s (1H, OH), 4.61 br.s (1H, OH),
3.84 s (6H, OMe), 2.83 m (3H, CH2Ph), 2.55 m (1H,
P
47.9 ppm. Found, %: C 75.72; H 6.80; P 8.63.
C23H25O2P. Calculated, %: C 75.80; H 6.91; P 8.50.
Bis(2-phenylethyl)[hydroxy(4-hydroxy-3-meth-
oxyphenyl)methyl]phosphine oxide (IIIb). A mix-
ture of 0.5 g of phosphine oxide I and 0.27 g of
4-hydroxy-3-methoxybenzaldehyde (IIb) in 3 ml of
dioxane was stirred for 16 h at room temperature, and
then for 2 h at 60 C; the solvent was removed in a
vacuum, and the residue was washed with ether and
dried in a vacuum (1 2 mm) to obtain 0.77 g of a
viscous liquid. Its 31P NMR spectrum showed the
presence, in addition to the target phosphine oxide
IIIb ( 49.8 ppm), of bis(2-phenylethyl)phosphine
CH2Ph), 2.15 m (2H, CH2P), 2.00 m (2H, CH2P). 13
C
NMR spectrum (CD3OD), C, ppm: 149.35 s (1C, C3),
3
142.66 d (2C, Ci, JPC 13.0 Hz), 136.59 s (1C, C4),
129.62 s (4C, C , 129.23 s (2C, Co), 129.07 s (2C,
)
Co), 128.96 s (1C, C1), 127.42 s (2C, Cp), 105.17 d
3
1
[2C, C2(C6), JPC 4.5 Hz)], 72.33 d (1C, CH, JPC
84.7 Hz), 56.57 s (2C, OMe), 28.50 d (1C, CH2P,
1JPC 60.2 Hz), 28.29 s (1C, CH2Ph), 28.24 s (1C,
CH2Ph), 26.97 d (1C, CH2P, 1JPC 60.2 Hz). 31P NMR
oxide (P 31 ppm) and its oxidation product, bis(2-
P
spectrum (CDCl3):
47.3 ppm. Found, %: C 68.13;
phenylethyl)phosphonic acid ( 54.3 ppm, identified
P
P
H 6.74; P 6.99. C25H29O5P. Calculated, %: C 68.17;
H 6.64; P 7.03.
with a reference sample) in a ratio of 62:13:25.
Phosphine oxide IIIb was washed out from the start-
ing and by-products with several portions of ether
(5 0.5 ml) and dried in a vacuum to obtain 0.46 g
(62%) of phosphine oxide IIIb, mp 148 150 C
(hexane). 1H NMR spectrum (CD3OD), , ppm:
7.25 m (4H, Hm, Ph), 7.22 m (2H, Ho, Ph), 7.12 m
Bis[2-(2-pyridyl)ethyl][hydroxy(phenyl)methyl]-
phosphine oxide (V). A mixture of 0.18 g of phos-
phine oxide IV and 0.07 g of benzaldehyde (IIa) in
2 ml of methanol was stirred at room temperature for
30 h. The solvent was distilled off, the residue was
washed with ether (5 0.5 ml), and dried in a vacuum
to obtain 0.18 g (73%) of phosphine oxide V as a
(2H, Hp, Ph), 7.11 m (2H, Ho, Ph), 7.11 s (1H, H2),
3
6.95 d (1H, H6, JH H 8.1 Hz), 6.84 d (1H, H5),
5
6
2
1
5.01 d (1H, CH, JPH 7.1 Hz), 4.83 br.s (2H, OH),
yellow oily substance. H NMR spectrum (CDCl3), ,
3.84 s (3H, OMe), 2.84 m (3H, CH2Ph), 2.58 m (1H,
CH2Ph), 2.12 m (2H, CH2P), 1.98 m (2H, CH2P). 13C
NMR spectrum (CD3OD), C, ppm: 149.05 s (1C, C3),
ppm: 2.07 2.35 m (4H, HCH2), 2.55 m, 2.75 m,
2
2.95 m, 3.25 m (4H, PyCH2), 5.20 d (1H, CH, JPH
6.8 Hz), 7.00 7.70 m (11H, pyridine H3, H4, and H5;
3
147.72 s (1C, C4), 142.64 d (2C, Ci, JPC 13.0 Hz),
3
Ph), 8.05 d (2H, pyridine H2, JH H 7.2 Hz),
2
3
129.69 s (1C, C1), 129.65 s (4C, Cm), 129.22 s (2C,
Co), 129.09 s (2C, Co), 127.41 s (1C, Cp), 127.35 s
10.00 br.s (1H, OH). 31P NMR spectrum (CDCl3):
P
3
57.4 ppm. Found, %: C 68.37; H 6.29; N 7.69; P 8.23.
C21H23N2O2P. Calculated, %: C 68.84; H 6.33; N
7.65; P 8.45.
(1C, Cp), 120.69 d (1C, C6, JPC 4.6 Hz), 116.11 s
(1C, C5), 111, 56 d (1C, C2, 3JPC 3.5 Hz), 72.23 d (1C,
1
CH, JPC 82.8 Hz), 56.37 s (1C, OMe), 27.27 d (1C,
1
CH2P, JPC 60.2 Hz), 28.33 s (1C, CH2Ph), 28.24 s
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(1C, CH2Ph), 25.81 d (1C, CH2P, JPC 60.2 Hz). 31P
NMR spectrum (CDCl3):
70.20; H 6.60; P 7.25. C24H27O4P. Calculated, %: C
70.23; H 6.63; P 7.55.
49.8 ppm. Found, %: C
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residue (0.19 g) contained signals of unreacted bis(2-
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REACTION OF SECONDARY PHOSPHINE OXIDES
1357
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