Reactions of p-hydroxyphenylphosphine and functionally substituted bis(hydroxymethyl)phosphines with heterocumulenes

Article abstract of DOI:10.1023/B:RUGC.0000018643.28412.96

Reactions of p-hydroxyphenylphosphine, bis(hydroxymethyl)(p-hydroxyphenyl) phosphine, and bis(hydroxymethyl)(5-allyl-2-ethoxybenzyl)phosphine with nitrogen-containing heterocumulenes were studied. The competitive reactivity of the phenol, phosphine, and hydroxymethyl groups in these reactions was examined.

Full text of DOI:10.1023/B:RUGC.0000018643.28412.96

Russian Journal of General Chemistry, Vol. 73, No. 11, 2003, pp. 1691 1695. Translated from Zhurnal Obshchei Khimii, Vol. 73, No. 11, 2003,
pp. 1787 1792.
Original Russian Text Copyright
2003 by Baimukhametov, Zheltukhin, Ignat’eva, Balueva, Nikonov, Sinyashin.
Reactions of p-Hydroxyphenylphosphine
and Functionally Substituted Bis(hydroxymethyl)phosphines
with Heterocumulenes
F. Z. Baimukhametov, V. F. Zheltukhin, S. N. Ignat’eva,
A. S. Balueva, G. N. Nikonov, and O. G. Sinyashin
Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center,
Russian Academy of Sciences, Kazan, Tatarstan, Russia
Received July 23, 2001
Abstract Reactions of p-hydroxyphenylphosphine, bis(hydroxymethyl)(p-hydroxyphenyl)phosphine, and
bis(hydroxymethyl)(5-allyl-2-ethoxybenzyl)phosphine with nitrogen-containing heterocumulenes were studied.
The competitive reactivity of the phenol, phosphine, and hydroxymethyl groups in these reactions was examined.
Primary and secondary phosphines readily react
with various nitrogen-containing heterocumulenes
(carbodiimides, isocyanates, isothiocyanates), attack-
ing the C=N bond and yielding functionally substi-
tuted phosphines with amidine, carbamoyl, and thio-
carbamoyl groups [1 3]. Several examples of addition
of bis(hydroxymethyl)organylphosphines to aryl iso-
cyanates, to give the corresponding bis(urethanometh-
yl)organylphosphines, have been reported. However,
the reaction is accompanied by substantial polymeri-
zation of the starting isocyanates [4]. These experi-
ments were performed with the phosphines and bis-
(hydroxymethyl)phosphine that contained no addition-
al functional groups. There is only one reported ex-
ample of the reaction of a functionally substituted
secondary phosphine, (2-mercaptoethyl)phenylphos-
phine, with phenyl isothiocyanate; the addition occurs
via secondary phosphino group only [1].
In view of these facts, we studied in this work the
reaction of nitrogen-containing heterocumulenes with
p-hydroxyphenylphosphine and bis(hydroxymethyl)-
(p-hydroxyphenyl)phosphine. These reactions could
be a route to new polyfunctional phosphines and their
derivatives. Our goal was to compare the reactivity of
the P H and O H groups in reactions with hetero-
cumulenes.
p-Hydroxyphenylphosphine I used in this work was
prepared by the scheme based on the reaction of
p-bromophenyl acetate with triethyl phosphite in the
presence of nickel(II) chloride [5]:
(EtO)2P(O)
P(OEt)3
Br
Br
(CH3CO)2O
NiCl2
OH
OC(O)CH3
OC(O)CH3
P(CH2OH)2
H2P
LiAlH4
2CH2O
HO
OH
I
II
Phosphine I is a low-melting crystalline substance;
II was prepared by reaction of I with 2 equiv of para-
form at 100 120 C without of a solvent. Compound
II is a thermally unstable noncrystallizing viscous
liquid. Its 31P NMR spectrum consisted of a single
it was isolated by distillation and characterized by 31P
1
and H NMR spectroscopy.
Bis(hydroxymethyl)(p-hydroxyphenyl)phosphine
signal,
23 ppm, which allowed us to use this
P
1070-3632/03/7311-1691$25.00 2003 MAIK Nauka/Interperiodica

1692
BAIMUKHAMETOV et al.
compound in further reactions without additional puri-
fication.
adding two more equivalents of the isocyanate to the
reaction mixture, the signals of the primary and sec-
ondary phosphines (
127.3 and 47.68 ppm) dis-
P
First, we studied addition of I to isocyanates. We
found that the reaction of I with 1 equiv of 1-naphthyl
appear, and only the signal of the tertiary phosphine
(
1.9 ppm) remains in the spectrum. Further heating
ofP the reaction mixture at 60 C for several hours
caused no changes in the 31P NMR spectrum. We
failed to isolate the phosphine pure. However, storage
of the reaction mixture at 4 7 C resulted in precipi-
tation of a small amount of a crystalline substance; its
IR spectrum contained absorption bands of the N H
isocyanate yields more than one product. The 31P
NMR spectrum of the reaction mixture consists of
three signals: that of the starting primary phosphine,
127.3 ppm; a strong signal of a secondary phos-
pPhine (probably, the product of addition of one
isocyanate molecule at the phosphino group),
P
1
1
(3284 cm ) and C=O (1636 cm ) bonds of the car-
bamoyl moiety and of the P=O group (1220 cm ).
The 31P NMR spectrum of this product consisted of a
47.68 ppm; and a signal of a tertiary phosphine
(probably, the product of addition of two or three
1
heterocumulene molecules),
1.9 ppm. The ratio of
P
1
the integral intensities of these signals was 2 : 3 : 1.
The reaction is accompanied by formation of a small
amount of a high-melting crystalline precipitate. The
31P NMR spectrum of this precipitate contains a sig-
single signal at 58 ppm, and the H NMR spectrum
contained only a complex multiplet of aromatic ring
protons at 6.76 8.3 ppm. The OH signal at 9 10 ppm
was absent. The analytical data correspond to the 1 : 3
(phosphine : naphthyl isocyanate) addition product.
These results allow us to identify this compound as
di(N-naphthylcarbamoyl)(4-naphthylurethanophenyl)-
phosphine oxide IV, product of oxidation of the ini-
tially formed tertiary phosphine.
nal with
14.43 ppm. The 31P NMR data in combi-
nation witPh analytical data allow us to identify this
substance as (N-naphthylcarbamoyl)(4-hydroxyphen-
yl)phosphinic acid III; it is presumably formed by
oxidation of the initially formed monoadduct. On
H
C10H7N=C=O
HO
P
HO
HO
PH2
C NHC10H7
[O]
O
2C10H7N=C=O
[O]
O
O
OH
O
O
P
C NHC10H7
C NHC10H7
O
P
C NHC10H7 C10H7NH CO
O
III
IV
1
1
Our results suggest that the first reaction step is
addition of one isocyanate molecule to the phosphino
group.
(1250 cm ) and C=O (1630 cm ) groups, and also
1
1
broad N H stretching bands (3320 cm ). The H
NMR spectrum contains no OH signals (9 10 ppm),
and the ratio of the integral intensities corresponds to
the presence of three benzylurethane fragments. The
analytical data also confirm this composition. Thus,
the isolated reaction product can be identified as di-
(benzylurethanomethyl)(4-benzylurethanophenyl)phos-
phine oxide V.
As the OH group in I is fairly reactive toward iso-
cyanates, in the experiments with bis(hydroxymethyl)-
(p-hydroxyphenyl)phoshine II we took 3 equiv of
heterocumulenes. We found that the reaction products
are readily oxidized with traces of oxygen, and only
the oxides were detected in the 31P NMR spectra.
With naphthyl isocyanate, polymerization prevailed,
and we failed to isolate phosphorus-containing prod-
ucts pure. With benzyl isocyanate, we obtained a
crystalline precipitate; its 31P NMR spectrum con-
A study of the reaction of II with diphenylcarbo-
diimide showed that the hydroxyphenyl group is less
reactive than the hydroxymethyl group. The IR spec-
trum of the crystalline precipitate isolated from the
reaction mixture contained the absorption bands of the
tained a signal with
33.7 ppm. The IR spectrum of
P
1
this compound contained absorption bands of the P=O
P=O group (1245 cm ), C=N bonds in the isourea
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

REACTIONS OF p-HYDROXYPHENYLPHOSPHINE
1693
HO
P(CH2OH)2
3PhCH2N=C=O
[O]
2PhN=C=NPh
[O]
NPh
CH2O C NHPh
CH2O C NHPh
NPh
O
O
P
O
O
P
CH2O C NHCH2Ph
CH2O C NHCH2Ph
O
HO
PhCH2NH CO
V
VI
1
1
moiety (1600 cm ), and N H bonds (3280 cm ).
only hydroxymethyl groups of II participate in the
reaction with carbodiimide.
The 31P NMR spectrum contained a signal with
34.32 ppm, and the H NMR spectrum contained,
P
1
Taking into account the fact that the reactions of
bis(hydroxymethyl)(p-hydroxyphenyl)phosphine II
with heterocumulenes were accompanied by fast oxi-
dation of trivalent phosphorus compounds, we per-
formed the reactions of isocyanates with a sterically
hindered substrate, (hydroxymethyl)(5-allyl-3-ethoxy-
benzyl)phosphine [6]. Its reaction with benzyl isocya-
nate, as monitored by 31P NMR spectrocsopy, is com-
along with a complex multiplet of aromatic protons
and a broad singlet originating from superposition of
the signals of the methylene and amine protons, also
a narrow singlet at 9.15 ppm belonging to the phenol
proton. The ratio of the signal intensities and analyti-
cal data suggest the presence of two N, N -diphenyl-
isourea fragments in the molecule. These data allow
the product to be identified as bis(1,3-diphenyliso-
ureomethyl)(4 -hydroxyphenyl)phosphine oxide VI,
an oxidation product of the initially formed adduct of
phosphine II with two carbodiimide molecules. Thus,
plete in 3 4 h. The 31P NMR spectrum of the reaction
mixture contains a signal with
24 ppm, apparently
P
corresponding to adduct VII:
X
OEt
OEt
CH2O C NH R
CH2P
2R N=C=X
CH2P(CH2OH)2
CH2O C NH R
All
E
All
X
VII, VIII
X
OEt
CH2O C NH R
E
CH2P
CH2O C NH R
X
All
VIIA, VIIIA
R = Bn (VII, VIIA), Ph (VIII, VIIIA); X = O (VII, VIIA), S (VIII, VIIIA); E = S (VIIA), O (VIIIA).
An attempt to isolate pure VII by precipitation
from hexane failed; only oxidation and decomposition
products were obtained. Therefore, the mixture con-
taining phosphine VI, after removing the solvent, was
treated with a solution of elemental sulfur in benzene.
The residue after removing excess sulfur and solvents
5-allyl-2-ethoxybenzyldi(benzylurethanomethyl)phos-
phine sulfide VIIA. The IR spectrum of VIIA con-
1
tained stretching bands of the N H (3256 cm ), C=O
1
1
(1728 cm ), and C=C (1596 cm ) bonds. The 31P
NMR spectrum consisted of a single signal with
42.47 ppm; the H NMR spectra was also consistent
P
1
1
was a viscous substance which, according to the H
with the suggested structure. The ratio of the integral
intensities of the signals corresponded to the presence
NMR, 31P NMR, and IR spectra, was identified as
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

1694
BAIMUKHAMETOV et al.
of one 5-allyl-2-ethoxybenzyl and two benzylure-
thanomethyl fragments in the molecule.
were distilled off, and the residue was fractionated.
Yield of p-bromophenyl acetate 74.5 g (67%), bp
114 C (10 mm). 1H NMR spectrum (CCl4),
,
The 31P NMR monitoring of the reaction of phenyl
isothiocyanate with bis(hydroxymethyl)(2-ethoxy-5-
allylbenzyl)phosphine showed that the signal of the
ppm (J, Hz): 2.16 s [3H, OC(O)CH3], 6.97 d (2H,
3
3
o-BrC6H4, JHH 9), 7.47 d (2H, m-BrC6H4, JHH 9).
Triethyl phosphite (57.52 g) was added dropwise
with stirring over a period of 2 h in a weak Ar flow
to a mixture of 74.5 g of p-bromophenyl acetate and
1.73 g of nickel(II) chloride, heated to 170 C; the
released ethyl bromide was distilled off. Fractionation
of the reaction mixture yielded 27.99 g (29.66%)
of diethyl p-acetoxyphenylphosphonate, bp 154 C
starting phosphine ( 21 ppm) gradually disappeared,
P
and signals with
26.9 and 44 ppm appeared. These
P
signals can be tentatively assigned to oxides of the
starting compound and initial reaction products, which
could not be separated by reprecipitation. Oxidation
of the product mixture with aqueous H2O2 yielded a
solid high-melting precipitate. Its IR spectrum con-
(0.1 mm). 31P NMR spectrum:
17 ppm.
1
P
tained stretching bands of the P=O group (1220 cm ),
1
A solution of 12.24 g of diethyl p-acetoxyphenyl-
phosphonate in 60 ml of diethyl ether was added at
stirring and cooling with ice to a suspension of 3.2 g
(50% excess) of LiAlH4 in 156 ml of diethyl ether.
The mixture was stirred for 6 h and decomposed, at
cooling with ice, with 6.07 ml of water and 29.33 ml
of 18% HCl. The organic layer was separated and
dried overnight over magnesium sulfate. The solvent
was removed, and the residue was vacuum-distilled.
Yield of p-hydroxyphenylphosphine I 2.46 g (43%),
bp 137 C (0.08 mm); colorless liquid crystallizing
C=C bonds in aromatic fragments (1600 cm ), and
1
N H bonds (3200 cm ). The 31P NMR spectrum
consisted of a single signal with
38.39 ppm, and
P
1
the H NMR spectrum suggested the presence of two
phenylthiocarbamatomethyl fragments. Based on the
spectral ana analytical data, the product was identified
as bis(phenylthiocarbamatomethyl)(5-allyl-2-ethoxy-
benzyl)phosphine oxide VIIIA.
Thus, our results show that bis(hydroxymethyl)or-
ganylphosphines readily add across the C=N bonds of
not only isocyanates but also other nitrogen-contain-
ing heterocumulenes: isothiocyanates and carbodi-
imides. The phenolic group, if present in the starting
phosphine molecule, is less reactive toward hetero-
cumulenes.
1
at room temperature. H NMR spectrum (C6D6), ,
1
ppm (J, Hz): 4.27 d (2H, PH2, JPH 199.6), 5.08 br.s
3
(1H, OH), 6.86 d (2H, OC6H4-o, JHH 7.7), 7.58 d.d
3
3
(2H, OC6H4-m, JHH 7.7, JPH 6.37). 31P NMR spec-
trum:
126.28 ppm (1JPH 198 Hz).
P
EXPERIMENTAL
Bis(hydroxymethyl)( p-hydroxyphenyl)phos-
phine II. Paraform (0.39 g) was added to 0.82 g of
p-hydroxyphenylphosphine; the mixture was heated
on a water bath to homogenization, after which it was
The IR spectra (mulls in mineral oil) were recorded
on a Specord M-80 spectrometer. The 31P NMR spec-
tra were taken on Bruker CXP-100 (36.5 MHz) and
Bruker MSL-400 (161 MHz) spectrometers, and the
1H NMR spectra, on a Bruker WM-250 spectrometer
(250 MHz). Bis(hydroxymethyl)(5-allyl-2-ethoxyben-
zyl)phosphine was prepared according to [6] from
5-allyl-2-ethoxybenzylphosphine.
cooled. 31P NMR spectrum:
23 ppm.
P
(N-Naphthylcarbamoyl)(4-hydroxyphenyl)phos-
phinic acid III and di(N-naphthylcarbamoyl)(4-
naphthylurethanophenyl)phosphine oxide IV. A
solution of 0.29 g of naphthyl isocyanate in 3 ml of
THF was added to a solution of 0.22 g of p-hydroxy-
phenylphosphine I in 5 ml of THF. The mixture was
refluxed for 30 min; the precipitate was filtered off.
Yield of III 0.2 g (38%), mp >260 C. 31P NMR spec-
All manipulations with phosphines were performed
in an inert atmosphere.
p-Hydroxyphenylphosphine I. Five drops of con-
centrated H2SO4 were added to a mixture of 90.42 g
of p-bromophenol and 58.69 g of acetic anhydride.
The mixture was heated for 3 h on a water bath,
cooled, and poured with stirring into ice-cold water.
A clotted precipitate formed (mp 21.5 C), which, after
decanting the liquid, was dissolved in toluene. The
aqueous phase was neutralized to weakly alkaline
reaction by adding sodium carbonate and extracted
with toluene; the combined organic layers were dried
over calcium chloride. The low-boiling components
trum (DMF):
14.43 ppm. Found, %: C 62.28; H
P
4.31; N 4.24; P 9.74. C17H14NO4P. Calculated, %:
C 62.38; H 4.28; N 4.28; P 9.48.
An additional 0.58-g portion of naphthyl isocya-
nate in 3 ml of THF was added to the filtrate; the
mixture was refluxed for 4 h. On standing, a precipi-
tate formed, which was filtered off and washed with
diethyl ether. Yield of IV 0.02 g (2%), mp 276 C. IR
1
spectrum (mull in mineral oil), , cm : 678, 770
1
(CHar), 1212 (P=O), 1556, 1636 (CO), 3284 (NH). H
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 73 No. 11 2003

REACTIONS OF p-HYDROXYPHENYLPHOSPHINE
1695
NMR spectrum (C6D6), , ppm (J, Hz): 6.76 8.3 m
(25H, C6H4 + C10H7). 31P NMR spectrum (DMF):
58 ppm. Found, %: C 74.05; H 4.76; N 7.24; P
4P.74. C39H28N3O4P. Calculated, %: C 73.93; H 4.42;
N 6.64; P 4.89.
filtered off. The filtrate was evaporated in a vacuum
(0.1 mm); the liquid oily residue was bis(benzyl-
urethanomethyl)(5-allyl-2-ethoxybenzyl)phosphine
sulfide VIIA. Yield 0.04 g (19%). IR spectrum (film
1
from CHCl3), , cm : 1536 (NH), 1596 (C=Car),
1
1728 (CO), 3256 (NH). H NMR spectrum (CDCl3),
Di(benzylurethanomethyl)(4-benzylurethano-
phenyl)phosphine oxide V. A solution of 0.25 g of
benzyl isocyanate in 3 ml of THF was added to a
solution of 0.12 g of bis(hydroxymethyl)(p-hydroxy-
phenyl)phosphine in 5 ml of THF. The mixture was
refluxed for 6 h, the solvent was removed in a vacuum,
and the residue was crystallized from diethyl ether.
Yield of V 0.06 g (16%), mp 128 130 C. IR spectrum
3
, ppm (J, Hz): 1.26 t (3H, CH3CH2O, JHH 6), 3.0
3.5 m (4H, PCH2Ar + NCH2CH=CH2), 3.55 4.8 m
(12H, PCH2O + OCH2CH3 + NCH2Ph + NH), 4.9
5.15 m (2H, CH2=CH), 5.7 6.0 m (1H, CH2=CH),
6.5 7.6 m (13H, C6H5 + C6H3). 31P NMR spectrum
(CH3CN):
42.47 ppm.
P
Bis(phenylthiocarbamatomethyl)(2-ethoxy-5-
allylbenzyl)phosphine oxide VIIIA. Paraform
(0.62 g) was added to 2.15 g of 5-allyl-2-ethoxyben-
zylphosphine. The mixture was heated to homogeniza-
tion and dissolved in 3 ml of THF; a solution of
2.71 g of phenyl isothiocyanate in 3 ml of THF was
added. The mixture was stirred for 6 h, and 5 ml of
hexane was added. After mixing, an emulsion formed,
which was allowed to separate. The lower layer was
evaporated in a vacuum, the residue was dissolved in
acetone, and a mixture of 0.5 g of 30% H2O2 and 2 ml
of acetone was added. The precipitate that formed
after standing for 24 h was filtered off. Yield of
VIIIA 0.02 g (6%), mp 187 C. IR spectrum (mull in
1
(mull in mineral oil), , cm : 1250 (P=O), 1580
1
(C=Car), 1630 (C=O), 3320 (NH). H NMR spectrum
(DMF-d7), , ppm (J, Hz): 4.1 4.5 m (PCH2O),
4.35 s (NCH2Ph) (total intensity 10H), 6.5 7.8 m
(22H, C6H5 + C6H4 + NH). 31P NMR spectrum
(DMF):
33.7 ppm. Found, %: C 63.17; H 5.10; N
P
7.02; P 6.48. C32H32N3O7P. Calculated, %: C 63.89;
H 5.32; N 6.98; P 6.15.
Bis(1,3-diphenylisoureomethyl)(4 -hydroxy-
phenyl)phosphine oxide VI. A solution of 0.25 g of
diphenylcarbodiimide in 3 ml of THF was added to a
solution of 0.08 g of bis(hydroxymethyl)(p-hydroxy-
phenyl)phosphine in 5 ml of THF. The mixture was
refluxed for 6 h, the solvent was evaporated, and the
residue was crystallized from diethyl ether. Yield of
VI 0.13 g (39%), mp 146 150 C. IR spectrum (mull
1
mineral oil), , cm : 688 (CHar), 1220 (P=O), 1376,
1552 (NH), 1600 (C=Car), 3050 3200 (NH). 1H NMR
spectrum (DMF-d7), , ppm (J, Hz): 1.42 t (3H,
3
CH3CH2O, JHH 6), 3.1 3.5 m (4H, PCH2Ar +
1
in mineral oil), , cm : 1245 (P=O), 1600 (C=N),
NCH2CH=CH2), 3.6 4.75
m
(6H, PCH2O
+
1
3280 (NH). H NMR spectrum (DMF-d7), , ppm
OCH2CH3), 4.85 5.1 m (2H, CH2=CH), 5.8 6.1 m
(1H, CH2=CH), 6.5 7.6 m (13H, C6H5 + C6H3). 31P
(J, Hz): 4.2 br.s (6H, PCH2O + NH), 6.55 7.87 m
(24H, C6H4 + C6H5), 9.15 s (1H, OH). 31P NMR
NMR spectrum (DMF):
38.39 ppm. Found, %: C
60.73; H 5.85; N 5.45;P P 5.70. C27H31N2O4PS2.
Calculated, %: C 59.77; H 5.71; N 5.17; P 5.71.
spectrum (DMF):
34.32 ppm. Found, %: C 70.73;
P
H 5.85; N 9.45; P 7.70. C34H30N4O3P. Calculated, %:
C 71.20; H 5.23; N 9.77 P 8.30.
REFERENCES
Bis(benzylurethanomethyl)(5-allyl-2-ethoxyben-
zyl)phosphine sulfide VIIA. Paraform (0.41 g) was
added to 1.43 g of 5-allyl-2-ethoxybenzylphosphine.
The mixture was heated to homogenization, after
which it was dissolved in 3 ml of THF, and a solution
of 1.83 g of benzyl isocyanate in 3 ml of THF was
added. The mixture was refluxed for 4 h. After cool-
ing, 5 ml of hexane was added; the emulsion obtained
after mixing was allowed to separate in two layers.
The upper layer was separated and evaporated in a
vacuum; a solution of 0.12 g of sulfur in benzene was
added to the residue. The mixture was heated for 4 h,
the solvent was removed, the residue was dissolved in
acetonitrile, and the precipitate of excess sulfur was
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