Reaction of (2-methoxyprop-2-yl)diphenylphosphine oxide with alkyl bromides

Article abstract of DOI:10.1016/j.mencom.2018.05.020

Treatment of (2-methoxyprop-2-yl)diphenylphosphine oxide with alkyl bromides affords alkyl(diphenyl)phosphine oxides in good yields.

Full text of DOI:10.1016/j.mencom.2018.05.020

Mendeleev
Communications
Mendeleev Commun., 2018, 28, 290–291
Reaction of (2-methoxyprop-2-yl)diphenylphosphine oxide
with alkyl bromides
Vasilii P. Morgalyuk,*a Tatyana V. Strelkova,a Nikolai D. Kagramanov,a
Alexander V. Artem’evb and Valery K. Brela
a A. N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences,
119991 Moscow, Russian Federation. Fax: +7 495 135 6549; e-mail: morgaliuk@mail.ru
b A. V. Nikolaev Institute of Inorganic Chemistry, Siberian Branch of the Russian Academy of Sciences,
630090 Novosibirsk, Russian Federation
DOI: 10.1016/j.mencom.2018.05.020
O
O
R
Ph
Ph
Me
Me
PPh2
Treatment of (2-methoxyprop-2-yl)diphenylphosphine oxide
with alkyl bromides affords alkyl(diphenyl)phosphine oxides
in good yields.
RBr
+
P
OMe
43–77%
R = n-C7H15, PhCH2, XC(O)CH2
The Michaelis–Arbuzov and Michaelis–Becker reactions are
widely used in the synthesis of organophosphorus compounds.1
However, the Michaelis–Arbuzov reaction requires the use of
trivalent phosphorus derivatives sensitive to hydrolysis and oxida-
tion,1(a),(b) whereas the Michaelis–Becker reaction comprises
application of strong bases.1(c) Therefore, the search for alternative
methods to form P–C bond remains urgent. We found previously2
that trimethylsilyl diphenylphosphinite, a potentially valuable
precursor for the Michaelis–Arbuzov reaction, can be prepared
quickly and in high yield by silylation of stable (2-hydroxyprop-
2-yl)diphenylphosphine oxide in 1,4-dioxane at 100°C. The use
of (2-hydroxyprop-2-yl)diphenylphosphine oxide in the syntheses
provided higher yields of the products compared with similar
syntheses based on ethyl diphenylphosphinite.3
Therefore, it was of interest to test methyl ether of the above-
mentioned (2-hydroxyprop-2-yl)diphenylphosphine oxide, namely,
(2-methoxyprop-2-yl)diphenylphosphine oxide 1.4 We found
that compound 1 did not react with silylating agents such as
hexamethyldisilazane, N,N-diethyl-N-(trimethylsilyl)amine, and
bis(trimethylsilyl)acetamide at 100–130°C. However, phosphine
oxide 1 reacted at 150–160°C in diglyme with n-heptyl bromide
2a and benzyl bromide 2b to furnish heptyl(diphenyl)phosphine
oxide 3a and benzyl(diphenyl)phosphine oxide 3b, respectively
(Scheme 1).† In case of n-heptyl bromide 2a, 2,2-bis(diphenyl-
phosphoryl)propane 4 isolated in 10% yield was also formed as
a by-product.
(dialkoxymethyl)phosphine oxides upon their lithiation5] along
with 2-methoxyprop-2-enium cation B (see Scheme 1). Phosphinite
anion A reacts further with alkyl halides 2 to form phosphine
oxides3. Incaseoflessreactiven-heptylbromide2a, replacement
of methoxy group in compound 1 also occurs to afford bis-phos-
phine dioxide 4.
To increase the reactivity of anion A by the separation the ion
pair A and B, tetrabutylammonium bromide (10 mol%) was added
O
Me
Me
Me
Me
Me
PPh2
OMe
150–160°C
diglyme
Ph2P–O
+
O
1
B
A
– Br–
O
Br–
RBr
2a–e
Me
Me
Ph
Yield
of 3 (%)
R
+
O
MeBr
P
R
Ph
a
b
c
d
e
n-C7H15
PhCH2
CH2CO2Et
CH2C(O)NEt2
CH2C(O)Ph
66
77
47
57
43
3a–e
O
PPh2
Me
Me
in case of 2a
+
PPh2
O
4 (10%)
Scheme 1
The observed reactivity of compound 1 can be explained by
its propensity to thermal cleavage of the phosphorus–carbon
bond to give diphenylphosphinite anion A [similarly to diphenyl-
(2-Methoxyprop-2-yl)diphenylphosphine oxide 1. 2,2-Dimethoxypropane
(5.18 g, 49.81 mmol, 10% excess) was added to diphenylphosphinous
chloride (5 g, 45.35 mmol) in heptane (20 ml) with stirring. After 2–3 min,
an exothermic reaction began with gas evolution. With the external cooling,
the temperature of the reaction medium was maintained at 25–30°C.
After another 10–15 min, product 1 began to precipitate, and after 1 h gas
evolution almost ceased. The reaction mixture was left at 20°C for 18 h.
The precipitate 1 was filtered off and washed with heptane (2×5 ml).
Drying in air and then in a desiccator at 14 Torr afforded 5.84 g (94%) of
compound 1 as colourless needles, mp 151–152°C (lit.,4(b) mp 151–153°C).
31P NMR, d: 32.14 (s). 1H NMR, d: 7.97–7.92 (m, 4H, o-H, 2Ph), 7.37–7.28
(m, 6H, m,p-H, 2Ph), 3.13 (s, 3H, OMe), 1.30 (d, 6H, 2Me, 3JP,H 14.1 Hz).
Found (%): C, 69.94; H, 7.20; P, 11.26. Calc. for C16H19O2P (%): C, 70.06;
H, 6.98; P, 11.29.
†
1H and 31P NMR (d/ppm) spectra were recorded in CDCl3 on a Bruker
Avance 400 spectrometer operating at 400.13 and 161.98 MHz, respec-
tively. Chloroform-d was distilled over P2O5 and stored over K2CO3 at
0°C in the dark. All syntheses were performed in inert atmosphere. Alkyl
bromides 2a–d were used after distillation; phenacyl bromide 2e was
recrystallized from heptane; bis(diphenylphosphoryl)bromomethane 5 was
used as received. Column chromatography was carried out on silica gel
0.060–0.200 mm, 60 Å (Acros Organics). The mass spectra were measured
on a Finnigan Polaris Q spectrometer with an ion trap (EI, 70 eV). We
failed to obtain molecular ion for 2,2-bis(diphenylphosphoryl)propane 4,
therefore we performed elemental C, H, P analysis for this compound.
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
– 290 –

Mendeleev Commun., 2018, 28, 290–291
O
O
O
5, we obtained methylenebis(diphenylphosphine) dioxide 6, a
O
PPh2
PPh2
PPh2
product of degradation of thermally unstable expected tris(di-
phenylphosphoryl)methane (Scheme 2).‡ Attempted reactions
of alkyl bromides 2c–e and 5 at 150–160°C in the absence of
Bu4NBr led to complex mixtures.
1, Bu4NBr
Br
Ph2P
100–110°C
PPh2
O
PPh2
PPh2
O
O
5
6 (54%)
In summary, we have proposed a new alternative to the
Arbuzov–Michaelis reaction, which enables the one-stage syn-
thesis of alkyl(diphenyl)phosphine oxides from available and
stable (2-methoxyprop-2-yl)diphenylphosphine oxide 1. The results
herein obtained allow one to consider compound 1 as a hidden
form of diphenylphosphinite anion A. The starting compound 1
can be easily synthesized in an analytically pure form by a modi-
fied method4(b) in 94% yield by the interaction of commercially
available 2,2-dimethoxypropane with diphenylphosphinous chlo-
ride Ph2PCl.
Scheme 2
to the reaction system (cf. ref. 6). The use of Bu4NBr additive
allowed us to decrease reaction temperature to 100–110°C and
to involve a-functionalized alkyl bromides 2c–e into the reaction
(see Scheme 1). In this manner, functional derivatives 3c–e were
accessed.‡ On moving to bis(diphenylphosphoryl)bromomethane
Compounds 3a and 4 (general procedure). n-Heptyl bromide 2a (0.78 g,
4.36 mmol, 20% excess) was added to compound 1 (1 g, 3.65 mmol)
in diglyme (4 ml). The mixture was heated at 150–160°C for 2 h, with
evolved acetone being distilled off. The mixture was cooled to 20°C,
diluted with CH2Cl2 (10 ml), washed with water (2×10 ml), and dried
with MgSO4. The drying agent was separated by filtration, washed with
CH2Cl2 (2×5 ml), and the filtrate was concentrated. Column chromato-
graphy on silica gel in chloroform–acetone eluent (10:1 and next 5:1)
gave products 3a and 4 in yields of 0.72 g (66%) and 0.15 g (10%),
respectively.
Heptyl(diphenylphosphine) oxide 3a, mp 61–62°C, (lit.,7(a) 61–62°C).
31P NMR, d: 32.57 (s). 1H NMR, d: 7.82–7.67 (m, 4H, o-HPh), 7.49–7.40
(m, 6H, m,p-HPh), 2.25–2.12 (m, 2H, P–C1H2), 1.63–1.53 (m, 2H, C2H2),
1.38–1.31 (m, 2H, C3H2), 1.24–1.15 (m, 6H, C4H2 +C5H2 +C6H2), 0.81
(t, 3H, Me, 3JH,H 7.0 Hz) [cf. ref. 7(b)]. MS, m/z: 300 [M]+.
2,2-Bis(diphenylphosphoryl)propane 4, semihydrate, mp 265–267°C,
(lit.,8 mp 270–271°C for anhydrous form). 31P NMR, d: 29.97 (s). 1H NMR,
d: 7.73–7.77 (m, 8H, o-HPh), 7.52–7.42 (m, 12H, m,p-HPh), 2.14 (s, 1H,
0.5H2O), 2.00 (d, 6H, 2Me, 3JP,H 13.0 Hz). Found (%): C, 71.60; H, 6.32;
P, 13.35. Calc. for C27H26P2O2 ·0.5H2O (%): C, 71.51; H, 6.00; P, 13.66.
Benzyl(diphenyl)phosphine oxide 3b was obtained similarly, the eluent
was chloroform–acetone, 10:1. Yield 77%, mp 191–193 °C (lit.,9(b)
mp 192–193°C). 31P NMR, d: 29.31 (s) (cf. ref. 9).1H NMR, d: 7.69–7.65
(m, 4H, o-H, 2PhP), 7.51–7.47 (m, 2H, p-H, 2PhP), 7.44–7.39 (m, 4H,
m-H, PhP), 7.18–7.15 (m, 3H, m,p-H, CH2Ph), 7.10–7.07 (m, 2H, o-H,
CH2Ph), 3.64 (t, 2H, CH2Ph, 2JP,H 13.8 Hz) (cf. ref. 9). MS, m/z: 292 [M]+.
The contribution of Center for Molecular Composition Studies
of A. N. Nesmeyanov Institute of Organoelement Compounds,
Russian Academy of Sciences is gratefully acknowledged.
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‡
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Ethyl 2-(diphenylphosphoryl)acetate 3c. Yield 47%, mp 73–76°C,
(lit.,2 mp 75–77°C). 31P NMR, d: 24.64 (s). 1H NMR, d: 7.77–7.52
(m, 4H, o-HPh), 7.50–7.42 (m, 6H, m,p-HPh), 3.94 (q, 4H, OCH2Me,
3JH,H 5.3 Hz), 3.44 (d, 2H, PCH2, 2JP,H 11.3 Hz), 0.97 (t, 3H, OCH2Me,
3JH,H 5.3 Hz) (cf. refs. 2, 10). MS, m/z: 288 [M]+.
N,N-Diethyl-2-(diphenylphosphoryl)acetamide 3d.Yield 57%, mp 172–
175°C (lit.,11 mp 173–175°C). 31P NMR, d: 28.30 (s). 1H NMR, d:
7.88–7.83 (m, 4H, o-H, 2Ph), 7.52–7.43 (m, 6H, m,p-H, 2Ph), 3.54 (d,
2H, PCH2, 2JP,H 15.7 Hz), 3.39 (q, 2H, NCH2, 3JH,H 7.1 Hz), 3.23 (q, 2H,
3
3
NCH2, JH,H 7.1 Hz), 1.11 (t, 3H, Me, JH,H 7.1 Hz), 0.89 (t, 3H, Me,
3JH,H 7.1 Hz) (cf. ref. 11). MS, m/z: 305 [M]+.
2-Diphenylphosphoryl-1-phenylethan-1-one 3e.Yield 43%, mp 137–140°C
(lit.,12(a) mp 138–140°C). 31P NMR, d: 27.05 (s). 1H NMR, d: 7.98–7.96
[m, 2H, o-H, PhC(O)], 7.82–7.77 (m, 4H, o-H, 2PhP), 7.52–7.49 [m,
3H, m,p-H, PhC(O)], 7.47–7.40 (m, 6H, m,p-H, 2PhP), 4.13 (d, 2H,
CH2, 2JP,H 15.4 Hz) [cf. ref. 12(b)]. MS, m/z: 320 [M]+.
Methylenebis(diphenylphosphine) dioxide 6 was obtained similarly to
compounds 3c–e from compound 1 and bis(diphenylphosphoryl)bromo-
methane 5. Yield 54%, mp 180–182°C (lit.,2 mp 180–182°C). 31P NMR,
d: 24.69 (s). 1H NMR, d: 7.77–7.72 (m, 8H, o-H, 2Ph), 7.46–7.42
(m, 4H, p-H, 2Ph), 7.38–7.34 (m, 8H, m-H, 2Ph), 3.54 (t, 2H, CH2,
2JP,H 14.8 Hz) (cf. refs. 2, 13). MS, m/z: 416 [M]+.
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Received: 13th October 2017; Com. 17/5374
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