Synthesis of (4-hydroxy-3,5-di-tert-butylphenyl)- chloromethanediphenylphosphine oxide and its reactions with aprotic nucleophilic reagents

Article abstract of DOI:10.1134/S1070363214040094

Reaction of (4-hydroxy-3,5-di-tert-butylphenyl) chloromethanediphenylchlorophosphonium chloride with trimethyl orthoformate affords (4-hydroxy-3,5-di-tert-butylphenyl)chloromethanediphenylphosphine oxide. The latter undergoes dehydrochlorination under the

Full text of DOI:10.1134/S1070363214040094

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 4, pp. 654–657. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © M.B. Gazizov, R.K. Ismagilov, R.F. Karimova, L.P. Shamsutdinova, R.N. Burangulova, S.Yu. Ivanova, 2014, published in Zhurnal
Obshchei Khimii, 2014, Vol. 84, No. 4, pp. 574–577.
Synthesis of (4-Hydroxy-3,5-di-tert-butylphenyl)-
chloromethanediphenylphosphine Oxide
and Its Reactions with Aprotic Nucleophilic Reagents
M. B. Gazizov, R. K. Ismagilov, R. F. Karimova,
L. P. Shamsutdinova, R. N. Burangulova, and S. Yu. Ivanova
Kazan National Research Technological University, ul. K. Marksa 68, Kazan, Tatarstan, 420015 Russia
e-mail: mukattisg@mail.ru
Received July 15, 2013
Abstract―Reaction of (4-hydroxy-3,5-di-tert-butylphenyl)chloromethanediphenylchlorophosphonium chloride
with trimethyl orthoformate affords (4-hydroxy-3,5-di-tert-butylphenyl)chloromethanediphenylphosphine oxide.
The latter undergoes dehydrochlorination under the action of trimethyl orthoformate and O-methyl diethyl-
phosphinate, and with diphenylchloro- and triphenyl phosphines it gives the corresponding phosphonium salts.
Keywords: diphenylphosphine oxide, dehydrochlorination, phosphines, phosphonium salts, trimethyl orthoformate
DOI: 10.1134/S1070363214040094
It was found previously that the reaction of
equimolar amounts of 4-hydroxy-3,5-di-tert-butyl-
benzylidene chloride with diphenylchlorophosphine
led to the formation of (4-hydroxy-3,5-di-tert-butyl-
phenyl)chloromethanediphenylchlorophosphonium
chloride (I) [1]. This salt under the action of sulfur
dioxide or air moisture forms (4-hydroxy-3,5-di-tert-
butylphenyl)chloromethanediphenylphosphine oxide
(II). It is a promising starting reagent for the synthesis
of phosphorylated derivatives of sterically hindered
phenols which may exhibit antioxidant and biological
activity.
We have found that salt I reacts with trimethyl ortho-
formate III with heat evolution. The main product of
the reaction of equimolar amounts of compounds I and
III is phosphine oxide II. We presume that trimethyl
orthoformate substitutes the phosphorus-bound chlorine
atom with a methoxy group. Intermediate quasiphos-
phonium salt IV is stabilized by the formation of (4-
hydroxy-3,5-di-tert-butylphenyl)chloromethanediphenyl-
phosphine oxide (II) (Scheme 1).
With the purpose of synthesis of new phos-
phorylated derivatives of sterically hindered phenols
Scheme 1.
t-Bu
HO
t-Bu
t-Bu
+
+
− + [CH(OMe)2Cl]
Cl
Cl−
HO
t-Bu
CH
Cl
+ MeOCH(OMe)2
CH
Cl
PPh2
P(OMe)Ph2
Cl
III
I
IV
t-Bu
CH
Cl
+ 2MeCl + HC(O)OMe
HO
P(O)Ph2
t-Bu
II
654

SYNTHESIS OF (4-HYDROXY-3,5-DI-tert-BUTYLPHENYL)…
655
Scheme 2.
t-Bu
+
(MeO)2CHOMe
H O
t-Bu
CH
Cl
P(O)Ph2
II
t-Bu
O
CH
P(O)Ph2 + MeCl + HC(O)OMe + MeOH
t-Bu
V
Scheme 3.
t-Bu
O
t-Bu
OH
+ Cl−[Me−O−P+Ph2]
Et2(MeO)P=O + H
CH
Cl
O
CH P(O)Ph2
P(O)Ph2
t-Bu
t-Bu
II
VI
V
t-Bu
O
CH
P(O)Ph2 + MeCl + Et2P(O)OH
t-Bu
V
phosphine oxide II was involved in the reaction with a
series of aprotic nucleophilic reagents like trimethyl
orthoformate, O-methyl diethylphosphinate, diphenyl-
chlorophosphine, and triphenylphosphine.
experimentally. Refluxing a suspension of salt I in
benzene with trimethyl orthoformate in 1 : 15 molar
ratio for 2.5–3 h gives 4-(diphenylphosphinylme-
thylene)-2,6-di-tert-butylcyclohexadien-2,5-one (V) in
a good yield.
We have found that trimethyl orthoformate III in
the reaction with compound II shows a dehydro-
chlorinating activity. Heating of phosphine oxide II
with a large excess of orthoester III at 110–120°C for
2.5–3 h leads to the formation of 4-(diphenyl-
phosphinylmethylene)-2,6-di-tert-butylcyclohexadien-
2,5-one (V) (Scheme 2).
Compound V was prepared also by the reaction of
phosphine oxide II with O-methyldiethylphosphinate
VI (Scheme 3).
Formerly, we discovered dehydrohalogenating re-
activy of P(IV) acid esters on an example of inter-
action of compound IV with polybromoethanes [3].
The result of the reaction between compounds II
and III is a rare example of dehydrochlorinating reactivity
of trialkyl orthoformates. Formerly, we discovered this
property of the orthoethers on the examples of their
interaction with tetra- and pentabromoethanes to form
tri- and tetrabromoethylenes [2].
We have also studied the reactions of prosphine
oxide II with diphenylchlorophosphine and triphenyl-
phosphine, the compounds exhibiting nucleophilic
properties [1, 4, 5]. Diphenylchlorophosphine adds
compound II to give salt VII. Treating phosphine
oxide II with trimethyl orthoformate results in the
formation of 4-hydroxy-3,5-di-tert-butylphenylme-
thanebis(diphenylphosphine oxide) (VIII) (Scheme 4).
The sequence of chemical transformations
presented above suggests that compound V may be
synthesized by a direct reaction of salt I with a large
excess of trimethyl orthoformate. This we confirmed
Triphenylphosphine quarternizes phosphine oxide
II to give (4-hydroxy-3,5-di-tert-butylphenyl)(diphenyl-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

656
GAZIZOV et al.
Scheme 4.
t-Bu
HO
t-Bu
t-Bu
HO
t-Bu
P(O)Ph2 Cl−
PPh2Cl
VII
CH
P(O)Ph2 + Ph2PCl
CH
+
Cl
II
t-Bu
HO
t-Bu
HC(OMe)3
CH[P(O)Ph2]2 + MeCl + HC(O)OMe
VIII
Scheme 5.
t-Bu
HO
t-Bu
t-Bu
CH
HO
t-Bu
CH
+
P(O)Ph2
PPh3 Cl−
IX
P(O)Ph2 + PPh3
Cl
II
2
phosphinyl)methanetriphenylphosphonium chloride in
a high yield (Scheme 5).
ppm: 1.48 s [18H, C(CH3)3], 5.45 d (1H, CHP, JPH
6.5 Hz), 7.12 d (2H, C6H2, 3JHH 2 Hz), 7.40–8.20 m (10H,
C6H5). 31P NMR spectrum (acetonitrile): δP 28.96 ppm.
The structure of compounds II, V, VIII was
confirmed by the identity of the IR spectra of the
compounds obtained to those of authentic samples, and
also by the absence of the melting point depression in
the case of mixed samples.
4-(Diphenylphosphinylmethylene)-2,6-di-tert-
butylcyclohexadien-2,5-one (V). a. A mixture of
1.14 g (0.0025 m) of phosphine oxide II and 3.98 g
(0.0375 mol) of orthoester III was boiled for 3 h at
110–120°C. After cooling of the reaction mixture
crystals were formed. They were filtered off to obtain
0.87 g (83.6%) of product V, mp 219–221°C (iso-
octane–toluene) (219–221°C [6]). IR spectrum, ν, cm–1:
EXPERIMENTAL
1H NMR spectra were recorded on a Tesla BS-
567A (100 MHz) instrument. 31P NMR spectra were
obtained on a CXP-100 (36.5 MHz) spectrometer.
Chemical shifts of hydrogen are given with respect to
TMS, and of phosphorus, to 85% phosphoric acid.
1
1650, 1630 (C=O), 1590 (C=CH), 1250 (P=O). H
NMR spectrum (CCl4 + CDCl3), δ, ppm: 1.30 s [18H,
C(CH3)3], 6.45 d (1H, CHP, 2JPH 22.5 Hz), 6.83 s, 8.30 s
(2H, HC=C), 7.62 m (10H, C6H5).
IR spectra were recorded on a Perkin Elmer
Spectrum 65 spectrometer from KBr pellets or mulls in
mineral oil.
b. While pouring of 7.96 g (0.075 mol) of ortho-
ester III to 2.55 g (0.005 mol) of the salt I warming up
of reaction mixture to 30°C took place. At the sub-
sequent heating of the reaction mixture to 90–100°C
the starting salt dissolved for 15–25 min with the
liberation of gaseous methyl chloride. The reaction
mixture was boiled for 2.5–3 h, cooled, and 1.45 g of
precipitated crystals of product V was isolated, yield
69.4%, mp 219–221°C (isooctane–toluene).
(4-Hydroxy-3,5-di-tert-butylphenyl)chloromethane-
diphenylphosphine oxide (II). A mixture of 4.18 g
(0.008 mol) of salt I and 0.87 g (0.008 mol) of
orthoester III was refluxed for 30 min in 25 mL of
benzene until complete dissolution of the starting salt
I. After removing volatile products in a vacuum 3.03 g
(81.8%) of compound II was obtained, mp 182–185°C
(from toluene). IR spectrum, ν, cm–1: 3410 br (OH),
c. A solution of 1.82 g (0.04 mol) of phosphine
oxide II and 0.54 g (0.04 mol) of O-methyl diethyl-
1
1239 (P=O). H NMR spectrum (CCl4 + CDCl3), δ,
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 4 2014

SYNTHESIS OF (4-HYDROXY-3,5-DI-tert-BUTYLPHENYL)…
657
1
phosphinate in 5 mL of benzene was boiled for 5 h.
Filtering off the crystalline product which precipitated
after cooling and after removing of solvent from the
mother liquor gave 1.62 g (91%) of compound V, mp
218–220°C (isooctane–toluene).
obtained, 1.02 g (79%), mp 239–241°C. H NMR
spectrum (CCl4 + CDCl3), δ, ppm: 1.38 s [9H, C(CH3)3,
5.12 s (1H, OH), 7.15–8.25 m (25H, C6H5), 8.30–8.57
2
2
m (2H, C6H2), 8.75 d.d (1H, CH, JPH 7.23 Hz, JPH
4.05 Hz). Found, %: P 8.65, 8.95: Cl 5.05, 5.10.
C45H47O2P2Cl2. Calculated, %: P 8.64, Cl 4.95.
(4-Hydroxy-3,5-di-tert-butylphenyl)(diphenyl-
phosphinyl)methanediphenylchlorophosphonium
chloride (VII). A solution of 1.14 g (0.0025 mol) of
phosphine oxide II and 0.55 g (0.0025 mol) of
diphenylchlorophosphine in 20 mL of benzene was
boiled for 6 h. The residue after removing off benzene
in a vacuum was ground to powder to give 1.69 g of
salt VII, mp 58–63°C. 31P NMR spectrum (aceto-
nitrile), δP, ppm: 27.67 (P-phosphine oxide), 34.05 (P-
phosphonium). Found, %: Cl 10.65, 10.78; P 9.54,
9.39. C39H42O2P2Cl2. Calculated, %: Cl 10.52, P 9.19.
ACKNOWLEDGMENTS
The work was carried out with the financial support
of the Russian Foundation for Basic Research (grant
no. 13.03-97098/2013).
REFERENCES
1. Gazizov, M.B., Ismagilov, R.K., Shamsutdinova, L.P.,
Karimova, R.F., Musin, R.Z., Nikitina, K.A., Bash-
kirtsev, A.A., and Sinyashin, O.G., Russ. J. Gen. Chem.,
2012,vol. 82, no. 9, p. 1587.
2. Gazizov, M.B., Chernova, O.M., Karimova, R.F.,
Gazizov, K.M., Khazeeva, E.R., and Sinyashin, O.G.,
Russ. J. Gen. Chem., 2006, vol. 76, no. 7, p. 1170.
(4-Hydroxy-3,5-di-tert-butylphenyl)methanebis-
(diphenylphosphine oxide) (VIII). A mixture of
1.69 g (0.0025 mol) of salt VII and 0.27 g (0.0025 mol)
of orthoester III was boiled in 20 mL of benzene. In
the course of 1 h a gradual dissolution of starting salt
VII and liberation of methyl chloride was observed.
After removing of volatile products in a vacuum 1.08 g
(69.7%) of bisphosphine oxide VIII was obtained, mp
258–262°C (toluene) (263–266°C [7]).
3. Gazizov, M.B., Chernova, O.M., Karimova, R.F.,
Gazizov, K.M., Pudovik, M.A., and Sinyashin, O.G.,
Russ. J. Gen. Chem., 2006, vol. 76, no. 7, p. 1172.
4. De’Ath, N.J., Miller, J.A., and Nunn, M.J., Tetrahedron
Lett., 1973, no. 52, p. 5191.
5. Andriyashin, V.V., Bakhtiyarova, Yu.V., Cherkasov, R.A.,
Galkin, V.I., and Galkina, I.V., Russ. J. Org. Chem.,
2012, vol. 48, no. 12, p. 1574.
[(4-Hydroxy-3,5-di-tert-butylphenyl)(diphenyl-
phosphinyl)methane]triphenylphosphonium chlo-
ride (IX). A solution of 0.82 g (0.0018 mol) of
phosphine oxide II and 0.47 g (0.0018 mol) of
triphenylphosphine in 25 mL of benzene was boiled
for 20 min and allowed to stand for 24 h at room
temperature. Colorless crystals of compound IX were
6. Ismagilov, R.K., Moskva, V.V., Arkhipov, V.P.,
Ivantsov, A.E., and Kopylova, L.Yu., Zh. Obshch.
Khim., 1991, vol. 61, no. 9, p. 387.
7. Gasisov, M.B., Ismagilov, R.K., Shamsutdinova, L.P.,
Karimova, R.F., Bashkirtsev, A.A., and Sinyashin, O.G.,
Russ. J. Gen. Chem., 2010, vol. 80, no. 3, p. 533.
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