Synthesis of Phosphorus-Containing Podands―Analogs of Diglycolamide Based on Diphenyl- and Dibutylphosphorylmethanol under Phase Transfer Catalysis Conditions

Article abstract of DOI:10.1134/S107036321809013X

A convenient method for preparation of phosphorus-containing podands R₂P(O)CH₂OCH₂X, where X = C(O)NBu₂; P(O)R′₂, R = R′ = Ph, Bu, R = Ph, R′ = Bu via OH-alkylation of phosphorylmethanols under the ph

Full text of DOI:10.1134/S107036321809013X

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 9, pp. 1842–1849. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © A.V. Kharlamov, S.K. Belus, O.I. Artyushin, N.A. Bondarenko, 2018, published in Zhurnal Obshchei Khimii, 2018, Vol. 88, No. 9,
pp. 1498–1505.
Synthesis of Phosphorus-Containing Podands―
Analogs of Diglycolamide Based on Diphenyl-
and Dibutylphosphorylmethanol
under Phase Transfer Catalysis Conditions
A. V. Kharlamova, S. K. Belusa, O. I. Artyushinb, and N. A. Bondarenkoa*
a Institute of Chemicals and High Purity Compounds, National Research Center “Kurchatov Institute,”
Bogorodskii val 3, Moscow, 107076 Russia
*e-mail: bond039@mail.ru
b Nesmeyanov Institute of Organolement Compounds, Russian Academy of Sciences, Moscow, Russia
Received July 5, 2018
Abstract―A convenient method for preparation of phosphorus-containing podands R2P(O)CH2OCH2X, where
X = C(O)NBu2; P(O)R' , R = R' = Ph, Bu, R = Ph, R' = Bu via OH-alkylation of phosphorylmethanols under the
2
phase transfer conditions in the presence of Cs2CO3 was developed. Carbamoyl-substituted dimethyl ethers
were synthesized via transformation of phosphorylmethanols to phosphorylmethoxyacetic acids, followed by
amidation. Symmetrical bisphosphoryl substituted dimethyl ethers were obtained by reaction of
phosphorylmethanols with tosyl chloride in the presence of Cs2CO3. The synthesis of unsymmetrical
substituted ether in the presence of Cs2CO3 was complicated by transesterification of phosphorylmethyl
tosylate resulting in the formation of symmetrical dimethyl ethers as byproducts.
Keywords: OH-alkylation, phosphoryl-containing podands, phosphorylmethanols, phosphoryl-methyl
tosylates, phosphorylmethoxyacetic acids
DOI: 10.1134/S107036321809013X
Investigation of diglycolamides R2NC(O)CH2O·
CH2C(O)NR2 have demonstrated their high extraction
ability in nitric acid medium toward trivalent actinide
and lanthanide cations [1–6].
phosphonates and phosphine oxides to form complexes
with alkali metal cations [8] and data on successful
alkylation of the hydrophosphoryl compounds R2P(O)H
[9–11] and phosphoryl containing CH-acids [11]
without phase transfer catalyst.
Сomplexing ability of ligands containing phos-
phoryl group is known to be higher in a varying degree
than that of their carbamoyl analogs [7]. Therefore, to
study the dependence of complexing properties of
compounds with such structure on replacement in
ligands of one or two carbamoyl groups by phosphoryl
ones and on the nature of substituents at the
phosphorus atom we synthesized phosphoryl analogs
of diglycolamides―mono- and bis-phosphoryl-
substituted methyl esters 1–5 via OH-alkylation of
diphenyl- and dibutylphosphorylmethanol 6 and 7 in a
heterogeneous liquid–solid system in the absence of
phase transfer catalyst (starting and target phosphoryl
compounds played role of the latter). The main
prerequisites for the lastmentioned improvement were
the data on the ability of the phosphoryl group of
O
O
O
O
1
2
R2P
O
CNBu2
R2 P
O
PR2
1, 2
3−5
R = Ph (1), Bu (2); R1 = R2 = Ph (3), Bu (4); R1 = Ph, R2 =
Bu (5).
The synthesis of dimethyl ethers 1 and 2 with phos-
phoryl and carbamoyl groups (Scheme 1) was based on
phase transfer OH-alkylation of phosphinylmethyl
alcohols1 6 and 7 with methyl chloroacetate in the
1
Previously, a convenient method for synthesis of alcohols 6 and 7
by PH-alkylation of diphenyl- [12] and dibutylphosphinous [13]
acids with formaldehyde in the presence of aqueous alkali in
benzene or DMSO, respectively, was developed.
1842

SYNTHESIS OF PHOSPHORUS-CONTAINING PODANDS
1843
Scheme 1.
O
O
Cl
COOMe, Cs2CO3, dioxane
R2P
O
COOMe
R2P
OH
60−65oC, 10 h
8, 9
6, 7
(1) NaOH, H2O
(2) HCl, H2O
O
O
O
(Bu2N)3P, toluene
R2P
O
COOH
R2P
O
CNBu2
110−115oC, 2 h
10, 11
1, 2
R = Ph (1, 6, 8, 10), Bu (2, 7, 9, 11).
Scheme 2.
O
O
O
O
O
Cs2CO3,dioxane
R2P
OH
R2P
O
PR2
R2P
OH + TsCl
R2P
12, 13
R = Ph (3, 12), Bu (4, 13).
OTs
100−105oC, 1−5 h
3, 4
6, 7
presence of Cs2CO3 (dioxane, 60–65°C, 10 h, reactant
ratio 1 : 2 : 2). Intermediate esters 8 and 9 formed in
90–95% yields (31P NMR data) were reacted without
isolation: alkaline hydrolysis followed by acidification
gave the corresponding phosphinylmethoxyacetic acids
10, 11 in 61–69% yields after recrystallization. Their
transformation into podands 1, 2 was performed via
previously described method10 using amidating agent
tris(dibutylamido)phosphite formed in situ from
phosphorus trichloride and dibutylamine in the
presence of triethylamine (Scheme 1).
the presence of K2CO3 (Scheme 3). The reaction was
completed after refluxing in acetone for 1 h. In the
case of diphenylphosphinylmethanol 6 ratio of the
starting reagents was 1 : 1 : 2, while to complete the
conversion of dibutylphosphinylmethanol 7 to the
corresponding tosylate 13 under the same conditions, a
twofold excess of tosyl chloride was required. Recrys-
tallization gave the target products in 70–80% yields.
The synthesis of unsymmetrical ether 5 was carried
out in a two-phase system via two ways (Scheme 4):
alkylation diphenylphosphinylmethanol 6 with dibutyl-
phosphinylmethyl tosylate 13 (path a) and alkylation
dibutylphosphinylmethanol 7 with diphenylphosphinyl-
methyl tosylate 12 (path b). It should be noted that
these reactions proceeded with complications. Thus,
the reaction of alcohol 6 with tosylate 13 (path a), in
the presence of Cs2CO3 (reagent ratio 1 : 1 : 2,
dioxane, 100–105°C, 5 h) resulted in a mixture of the
target unsymmetrical ether 5 (94%) and symmetrical
ones 3, 4 (3%). The 31P NMR spectrum of the reaction
mixture exhibited two signals attributed to the
phosphorus atoms of the target unsymmetrical ether 5
The single representative of bis-phosphoryl substituted
dimethyl ethers―α,α'-bis(diphenylphosphinyl)methyl
ether 3 was earlier prepared via phase transfer
alkylation of diphenylphosphinylmethanol 6 in the
presence of Cs2CO3 with diphenylphosphinylmethyl
tosylate 12 [15], prior obtained from alcohol 6 and
tosyl chloride in pyridine [16].
A more convenient one-pot phase transfer method
was developed by us for synthesis of symmetrical
ethers 3, 4 from phosphinylmethanols 6, 7 and tosyl
chloride in the presence of Cs2CO3 (reactant ratio 2 : 1–
1.15 : 4) (Scheme 2). In this case, tosylate 12 or 13
was formed in situ in the reaction medium. Refluxing
in dioxane for 1–5 h gave ethers 3 and 4 in 60% and
70% yields (after two recrystallizations).
Scheme 3.
O
O
K2CO3, acetone
R2P
OTs
R2P
OH + TsCl
For tosylates 12 and 13 used for synthesis of
unsymmetrical ether 5, a convenient preparative
method was developed by us: alcohols 6 and 7 were
reacted with tosyl chloride in a two-phase system in
55−60oC, 1 h
12, 13
6, 7
R = Ph (6, 12), Bu (7, 13).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1844
KHARLAMOV et al.
Scheme 4.
O
O
O
O
Ph2P OTs
Bu2P OTs
Bu2P
OH
Ph2P
OH
a
b
7
6
Cs2CO3, dioxane
100−105oC, 5 h
O
O
O
O
O
O
+
Ph2P
O
PPh2
Ph2P
O
PBu2
+
Bu2P
O
4
PBu2
3
5
a (3%), b (16%)
a (94%), b (68%)
a (3%), b (16%)
Scheme 5.
(1) NaH, dioxane, 20−30oC, 30 min
(2) tosylate 12, 100−105oC, 5 h
O
O
O
Ph2P
O
PBu2
Bu2P
OH
5
7
[δP 27.0 (Ph2P=O) and δP 46.2 ppm (Bu2P=O)], and
two signals attributed to the phosphorus atoms of the
symmetrical ethers 3 and 4 (δP 27.0 и 45.5 ppm,
Use of NaH instead of Cs2CO3 allowed to avoid the
formation of symmetrical products. In this case, a two-
step synthesis was carried out as a one-pot method
(Scheme 5): the conversion of the starting alcohol 7
into alcoholate (20–30°C, 30 min) and its subsequent
reaction with tosylate 12 (100–105°C, 5 h). According
to 31P NMR spectrum 100% conversion of alcohol 7
into ether 5 occurred. Recrystallization gave ether in
80% yield.
1
respectively). These data corresponded with the H
NMR spectrum of the treated reaction mixture. The
spectrum contained four doublet signals of methylene
protons of R2P(O)СН2-group: for one signal of
methylene protons of symmetrical ethers 3 (4.44 ppm,
2
2JРН =5.4 Hz) and 4 (δ 3.90 ppm, JРН = 6.7 Hz), and
two signals of the methylene protons of unsymmetrical
Structure and composition of the obtained com-
pounds were confirmed by the data of microanalysis
2
ether 5 [3.94 ppm, JРН = 6.4 Hz (R = Bu) and
4.39 ppm, 2JРН = 5.4 Hz (R=Ph)].
1
13
31
(Table 1) and H, C, and P spectroscopy (Table 2).
1
When less acidic dibutylphosphinylmethanol 7 was
used as the starting alcohol (Scheme 4, path b), the
content of each by-product 3, 4 in the reaction mixture
increased to 16%, and the yield of the target ether 5
was reduced to 68%. In this case, along with product 5
symmetrical ether 3 was isolated in 10% yield from the
reaction mixture. Its mixture with the sample obtained
via one-pot method from alcohol 6 and tosyl chloride
did not lead to the melting point depression.
The assignment of the proton signals in the Н NMR
spectra was performed using complete decoupling
from the 31Р nuclei, whereas the carbon signals were
assigned using НМВС and HSQC correlation spectra.
It was shown that the signals of both ether carbon
atoms in the obtained compounds 1–5, 10, and 11
(symmetrical and unsymmetrical) were split on the
3
phosphorus atom (1JCP and JCP via the oxygen atom),
and in the presence of the second phosphorus atom
(compounds 3–5) both carbon atoms exhibited the
same constants (Table 2); the spin system for each of
Formation of the symmetrical ethers 3 and 4 was
likely due to the appearance of tosylates 12 and 13 (in
reactions a and b, respectively) via transesterification
of the starting tosylates 13 and 12 with alcohols 6 and
7 under alkaline catalysis conditions. It is known that
the use of less acidic alcohol leads to an increase in
yield of transestherification product [17], causing a
decrease in yield of target unsymmetrical ether 5 in
reaction by path b.
13
them was the АМХ type (doublet of doublets). In C
NMR spectra of compounds 1, 2, 10, and 11, the ether
carbon atom signals were doublets with the spin-spin
1
3
interaction constants JCP = 70–80 and JCP = 8–10 Hz
(Table 2). To identify the phenyl meta-proton signals
and the doublet signals of the СН2Р groups with
phenyl and butyl substituents at the phosphorus atoms
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

SYNTHESIS OF PHOSPHORUS-CONTAINING PODANDS
1845
Table 1. Yields, melting points, and microanalysis data of compounds 1–5 and 10–13
Found, %
Calculated, %
H P
Comp.
no.
Formula
Yield, %
60
mp, °C (solvent)
С
H
P
C
a
1
71.5–72.5
68.93
8.03
7.75
C23H32NO3P2 68.81 8.03
7.71
(pentane–EtOAc)
2
3
73
60
Oilb
137.5–138.5d
63.19
–
11.27 8.46
C19H40NO3Pc 63.13 11.15 8.57
–
–
–
–
–
–
(EtOAc–benzene)
4
70
63
61
69
80
70
52–53
(pentane)
58.78
65.12
62.04
52.79
–
11.05 16.81
7.79 15.33
5.36 10.42
9.40 12.50
C18H40O3P2
C22H32O3P2
C15H15O4P
C11H23O4P
–
59.00 11.00 16.90
65.01 7.94 15.24
62.07 5.21 10.67
52.79 9.26 12.38
5
84.5–85.5
(hexane–EtOAc)
10
11
12
13
141.5–142.5
(methyl ethyl ketone)
88–89
(hexane–methyl ethyl ketone)
126.0–127.5e
(hexane–EtOAc)
–
–
–
–
–
55.5–57.0
55.75
7.94
9.04
C16H27O4PSf 55.47 7.86
8.94
(pentane–Et2O)
a
Found N, %: 3.50. Calculated N, %: 3.49. b Purified by column chromatography. c Found N, %: 3.81. Calculated N, %: 3.87. d mp 134–
136°C [15]. e mp 126.0–127.5°C [16]. f Found S, %: 9.21 Calculated S, %: 9.26
two-dimensional corrilation procedure (HMBC) was
used.
presence of Cs2CO3 without phase transfer catalyst
was developed. A simple and convenient method for
preparation of the tosylates from phosphorylmethanols
and tosyl chloride was developed.
Investigation of the extraction ability of the
podands 1–5 showed that successive replacement of
C(O)NAlk2 groups in the molecule of diglycolamide
by P(O)Ph2 ones led to an increase in the extraction
efficiency of Ln(III) from hydrochloric acid medium
when toluene was used as the diluent. Phosphoryl-con-
taining podand 2 possessed a higher extraction ef-
ficiency toward Ln(III) than tetraoctyldiglycolamide.
A considerable synergistic effect was observed for the
lanthanides(III) extraction in the presence of 4-benzoyl-
3-methyl-1-phenylpyrazol-5-one in the organic phase
containing neutral organophosphorus ligands 1 and 2
[18].
EXPERIMENTAL
1
13
31
The H, C, and P NMR spectra of the obtained
compounds were recorded in CDCl3 on a Bruker
Avance III NanoBay 300 and Bruker Avance 400
spectrometers operating at 300.28 and 400.13, 75.50,
and 100.61, 121.56, and 161.97 MHz, respectively.
The residual proton (7.28 ppm) and carbon atom
(76.91 ppm) signals from the deuterated solvent were
31
used as the internal standard. For the P spectra, 85%
solution of Н3РО4 in D2O was used as external
standard. Melting points were measured by shortened
Anschütz thermmeters in a special block using
capillaries.
In summary, in search for new diglycolamide
analogues exhibiting complexing and extraction ability
some phosphoryl-containing dimethyl ethers were
prepared via successive replacement of the carbamoyl
groups by phosphoryl ones. A simple method for OH-
alkylation of diphenyl- and dibutylphosphinylmethanol
with methyl chloroacetate and phosphorylmethyl-
tosylates in a heterogeneous liquid–solid system in the
The solvents were dried according to the known
procedures [19]. Powder K2CO3 and Cs2CO3 were
dried in vacuo (1 Torr) at 150°C for 3 h. Silica gel
(130–270 mesh, 60 Å, Aldrich) was used for column
chromatography.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1846
KHARLAMOV et al.
Table 2. 31Р, 1Н, and 13С NMR spectra (CDCl3) of compounds 1–5 and 10–13
Comp.
no.
δР, ppm
δ, ppm (J, Hz)
δС, ppm (J, Hz)
0.90–1.12 m (6H, CH3), 1.21–1.41 m (4H,
13.62 and 13.73 (СН3), 19.88 and 20.09 (CH2Me),
28.2
1
CH2Me), 1.43–1.61 m (4H, CH2Et), 3.07 t (2HA, 29.56 and 30.74 (CH2Et), 45.39 and 46.35
АВ-system, NCH2, 3JHH 7.5), 3.34 t (2HB, АВ-
system, NCH2, 3JHH 7.5), 4.35 s (2H,
(NCH2), 69.28 d (PCH2O, 1JCP 86.4), 71.09 d
(ОСH2С=O, 3JCP 9.5), 128.48 d (m-СH, 3JCP 12.1),
OCH2C=O), 4.50 d (2H, PCH2O, 2JPH 5.0), 7.48– 130.74 d (ipso-С, 1JCP 99.3), 131.40 d (o-СH, 2JCP
7.70 m (6H, m,p-СН), 7.84 d. d. d (4H, o-СН, 3JHH
8.3, 4JHH 1.7, 3JHP 12.1)
9.5), 132.06 d (p-СH, 4JCP 3.0), 167.70 (С=О)
0.92–1.10 m (12H, Me), 1.28–1.93 m (20H,
NCH2CH2CH2 + PCH2CH2CH2), 3.17 t (2HA,
АВ-system, NCH2, 3JHH 7.5), 3.35 t (2HB, АВ-
system, NCH2, 3JHH 7.5), 3.94 d (2H, PCH2O,
2JPH 6.4), 4.28 s (2H, OCH2C=O)
13.48 [CH3(CH2)3P], 13.64 and 13.70 [CH3(CH2)3N],
19.94 and 20.08 [MeCH2(CH2)2N], 23.06 d
[MeCH2(CH2)P, 3JCP 4.3], 24.09 d (EtCH2CH2P,
2JCP 14.5), 26.00 d (PrCH2P, 1JCP 65.1), 29.58 and
30.85 (EtCH2CH2N), 45.40 and 46.37 (CH2N),
66.93 d (PCH2O, 1JCP 79.4), 70.85 d (OСH2С=O,
3JCP 11.0), 167.53 (С=О)
47.5
2
3
4.44 d (4H, PCH2O, 2JPH 5.5), 7.32–7.48 m (8H, 71.98 d. d (PCH2O,1JCP 85.3, 3JCP 9.8), 128.75 d
27.1
46.0
m-СН), 7.50–7.60 m (4H, p-СН), 7.63 d. d. d
(m-СH, 3JCP 12.1), 130.64 d (ipso-С, 1JCP 100.4),
131.54 d (o-СH, 2JCP 9.8), 132.41 d (p-СH, 4JCP
1.5 Hz)
(8H, o-СН, 3JHH 8.4, 4JHH 1.5, 3JHP 12.8)
0.91 t (12H, Me, 3JHH 7.1), 1.32–1.80 m (24H,
PCH2CH2CH2), 3.89 d (4H, PCH2O, 2JPH 6.3)
13.47 (CH3), 23.14 d (MeCH2, 3JCP 4.3), 24.12 d
(EtCH2, 2JCP 14.3), 26.20 d (PrCH2P, 1JCP 65.4),
69.45 d. d (PCH2O,1JCP 77.1, 3JCP 10.2)
4
5
27.6 (PhPO) 0.90 t (6H, Me, 3JHH 7.2), 1.25–1.72 m (12H,
13.43 (CH3), 22.93 d (MeCH2, 3JCP 4.3), 24.02 d
PCH2CH2CH2), 3.96 d (2H, BuPCH2, 2JPH 6.6), (EtCH2, 2JCP 14.4), 25.97 d (PrCH2P, 1JCP 65.1),
4.42 d (2H, PhPCH2, 2JPH 5.3), 7.50–7.71 m (6H, 69.03 d. d (OCH2PBu,1JCP 76.2, 3JCP 10.4), 71.36
m-СН + p-СН), 7.76 d. d. d (4H, o-СН, 3JHH 8.4, d. d (PhPCH2O, 1JCP 84.8, 3JCP 10.6), 128.59 d
46.9 (BuPO)
(m-СH, 3JCP 11.8), 130.33 d (ipso-С, 1JCP 100.3),
131.21 d (o-СH, 2JCP 9.4), 132.33 d (p-СH, 4JCP 2.7)
4JHH 1.5, 3JHP 11.5)
4.25 s (2H, OCH2C=O), 4.58 d (2H, PCH2O, 2JHP 68.75 d (OCH2P, 1JCP 85.8), 70.06 d (OCH2C=O,
31.7
52.9
25.7
10
11
12
3
4.7), 7.50–7.70 m (6Н, m-СН + p-СН), 7.81 d. d. JCP 10.2), 128.67 d (m-СH, 3JCP 12.3), 129.19 d
3
d (4Н, o-СН, JHH 8.4, 4JHH 1.6, 3JHP 11.9), 8.91 (ipso-С, 1JCP 100.8), 131.50 d (o-СH, 2JCP 9.7),
s (1Н, OH)
132.56 d (p-СH, 4JCP 2.9), 171.40 (C=O)
0.96 t (6Н, СH3, 3JHH 7.3), 1.40–1.52 m (4H,
PCH2CH2CH2), 1.56–1.70 m (4H, PCH2CH2),
1.80–1.98 m (4H, PCH2), 4.02 d (2H, PCH2O,
13.45 (CH3), 22.80 d (MeCH2, 3JCP 4.4), 23.97 d
(EtCH2, 2JCP 14.3), 25.28 d (PrCH2P, 1JCP 65.2),
65.74 d (PCH2O, 1JCP 80.9), 69.72 d (OCH2C=O,
1
2JHP 5.5), 4.14 s (2H, CH2C=O), 8.50 s (1Н, OH) JCP 12.2), 171.27 (C=O)
2.43 s (3H, CH3), 4.60 d (2H, PCH2, 2JHP 7.2),
7.26 d (2Н, m-СНSArMe, 3JHH 8.1), 7.42–7.53 m
21.68 (CH3), 64.78 d (PCH2O, 1JCP 82.0), 128.17
(o-СНSArMe), 128.80 d (m-СНPh, 3JCP 12.3), 129.14
d (ipso-СPh, 1JCP 104.0), 129.98 (m-СНSArMe),
131.20 (ipso-CSO3), 131.50 d (o-СНPh, 2JCP 9.7),
132.81 d (p-СНPh, 4JCP 2.8), 145.52 (ipso-CMe)
(4Н, m-СНPh), 7.55–7.64 m (4Н, o-СНSArMe
+
p-СНPh), 7.72 d. d. d (4Н, o-СН, 3JHH 8.4, 4JHH
1.6, 3JHP 12.0)
0.86 t (6Н, CH3, 3JHH 7.1), 1.28–1.84 m (12H,
13.39 (CH3), 21.59 (CH3C6H4), 22.65 d (MeCH2,
45.9
13
PCH2CH2CH2), 2.44 s (3H, CH3C6H4), 4.11 d
3JCP 4.8), 23.93 d (EtCH2, 2JCP 14.4), 26.08 d
(2H, PCH2O, 2JHP 7.5), 7.36 d (2H, m-СН, 3JHH (PrCH2P, 1JCP 66.7), 62.10 d (PCH2O, 1JCP 73.3),
8.3), 7.77 d (2H, o-СН, 3JHH 8.3)
128.12 (o-СН), 130.06 (m-СН), 131.15 (ipso-
CSO3), 145.76 (ipso-CMe)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

SYNTHESIS OF PHOSPHORUS-CONTAINING PODANDS
1847
Diphenylphosphorylmethoxyacetic acid (10).
To a stirring mixture of 9.2 g (39.4 mmol) of methanol
6 [12] and 25.7 g (78.8 mmol) of Cs2CO3 in 50 mL of
dioxane 8.6 g (78.8 mmol) of methylchloroacetate was
added dropwise at 60–65°C. The mixture was stirred at
60–65°C for 10 h, the precipitate was filtered off and
washed with CHCl3 (2×10 mL). Combined filtrate was
concentrated in vacuo. A solution of 4.7 g
(117.5 mmol) of NaOH in H2O (8 mL) was added to
the residue. The mixture was refluxed for 15 min,
extracted with CHCl3 (2×20 mL) and acidified with
conc. HCl to pH 2. Precipitated oil was extracted with
CHCl3 (2×20 mL). The brown extract was dried over
anhyd. Na2SO4, decolorized by shaking up with silica
gel (3×1.0 g) followed by filtration, and concentrated
in vacuo. The pale yellow crystalline crude product
(10.0 g, 88%, mp 137.0–140.5°C) was twice recrys-
tallized from methyl ethyl ketone to give acid 10 as
colorless crystalline solid; yield 7.0 g (61%). Micro-
analysis and NMR data are given in Tables 1 and 2.
of methanol 7, 27.2 g (83.3 mmol) of Cs2CO3, 9.0 g
(83.3 mmol) of methyl chloroacetate, and 20 mL of
dioxane. The crude product (9.1 g, 83.7%) was twice
recrystallized from hexane–methyl ethyl ketone
mixture to give acid 11 as colorless crystalline solid;
yield 7.6 g (69%). Microanalysis and NMR data are
given in Tables 1 and 2.
α-Dibutylphosphoryl-α'-dibutylcarbamoyl dimethyl
ether (2) was prepared according to the known
procedure [14] from 2.08 g (8.3 mmol) of acid 11,
0.57 g (4.2 mmol) of PCl3, 1.60 g (12.6 mmol) of
Bu2NH, 1.26 g (12.6 mmol) of Et3N, and 20 mL of
toluene. The crude product was purified by column
chromatography (CHCl3–MeOH, 40 : 1) to give ether
2 as pale yellow oil; yield 2.19 g (73%). Microanalysis
and NMR data are given in Tables 1 and 2.
α,α'-Bis(diphenylphosphoryl) dimethyl ether (3).
A mixture of 2.2 g (9.6 mmol) of methanol 6 [12],
0.9 g (4.8 mmol) of TsCl, and 6.2 g (19.2 mmol) of
Cs2CO3 in 10 mL of dioxane was refluxed with stirring
for 1 h. The mixture was diluted with 15 mL of CHCl3
and 10 mL of H2O, the organic layer was separated,
successively washed with 5 mL of H2O, 5 mL of
diluted HCl (1 : 2), H2O (3×5 mL), 5 mL of saturated
aqueous solution of NaHCO3, 5 mL H2O, dried over
anhyd. Na2SO4 and concentrated in vacuo. The crude
product (2.1 g, 98%) was twice recrystallized from
EtOAc–benzene mixture to give ether 3 as colorless
crystalline solid; yield 1.3 g (60%). Microanalysis and
NMR data are given in Tables 1 and 2.
α-Diphenylphosphoryl-α'-dibutylcarbamoyl di-
methyl ether (1) was prepared according to the known
procedure [14] from 2.17 g (7.5 mmol) of acid 10,
0.51 g (3.7 mmol) of PCl3, 1.44 g (11.2 mmol) of
Bu2NH, 1.13 g (11.2 mmol) of Et3N, and 20 mL of
toluene. The crude product was twice recrystallized
from pentane–EtOAc mixture to give ether 1 as
colorless crystalline solid; yield 1.80 g (60%). Micro-
analysis and NMR data are given in Tables 1 and 2.
Dibutylphosphorylmethanol (7). A solution of
2.9 g (52.1 mmol) of KOH in 3 mL of H2O and then
34% aqueous solution of 1.6 g (52.1 mmol) of CH2O
were added dropwise with stirring at 20–45°C to a
solution of 10.0 g (52.1 mmol) of dibutylphosphinous
acid [13] in 10 mL of DMSO. After stirring for 1 h at
50°C, the reaction mixture was diluted with 50 mL of
H2O and extracted with CHCl3 (3×20 mL). The extract
was dried over anhyd. Na2SO4 and evaporated in
α,α'-Bis(dibutylphosphoryl) dimethyl ether (4) was
prepared similarly to ether 3 from 1.8 g (9.4 mmol) of
methanol 7, 1.0 g (5.4 mmol) of TsCl, and 6.1 g
(18.8 mmol) of Cs2CO3 in 10 mL of dioxane for 5 h.
The crude product (1.7 g, 100%) was twice recrys-
tallized from pentane to give ether 4 as hydroscopic
colorless crystalline solid; yield 1.2 g (70%). Micro-
analysis and NMR data are given in Tables 1 and 2.
1
vacuo. Yield 8.2 g (82%); plate yellow oil. H NMR
3
Diphenylphosphorylmethyl ester of p-toluene-
sulfonic acid (12). To a stirring refluxing mixture of
4.8 g (20.7 mmol) of methanol 6 [12] and 5.7 g
(41.4 mmol) of K2CO3 in 20 mL of acetone a solution
of 4.0 g (20.7 mmol) of TsCl in 15 mL of acetone was
added dropwise. The reaction mixture was refluxed
with stirring for 1 h, the precipitate was filtered off,
and washed with acetone (2×10 mL). Combined
filtrate was concentrated in vacuo. The crude product
(10.0 g, 100%) was recrystallized from a hexane–
EtOAc mixture to give tosylate 12 as colorless
spectrum, δ, ppm: 0.88 t (6Н, CH3, JHH = 7.3 Hz),
1.31–1.44 m (4H, PCH2CH2CH2), 1.45–1.61 m (4H,
PCH2CH2), 1.63–1.80 m (4H, PCH2), 3.82 d (2H,
2
PCH2O, JHP = 2.0 Hz), 5.53 s (1Н, OH). 13C NMR
spectrum, δС, ppm: 13.68 (СН3), 23.42 d (CH3CH2,
3JCP = 3.8 Hz), 24.34 d (CH3CH2CH2, 2JCP = 13.6 Hz),
25.42 d (CH2P, 1JCP = 37.7 Hz), 58.58 d (CH2O, 1JCP
75.8 Hz). 31P{1H} NMR spectrum: δР 50.4 ppm.
=
Dibutylphosphorylmethoxyacetic acid (11) was
prepared similarly to acid 10 from 8.0 g (41.7 mmol)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 9 2018

1848
KHARLAMOV et al.
crystalline solid, yield 8.0 g (80%). Microanalysis and
NMR data are given in Tables 1 and 2.
a boiling hexane–EtOAc mixture (1 : 1) and cooled
down to ambient temperature. Mother liquor then was
cooled to 0°C, second portion of precipitate (1.50 g)
was filtered off. The first portion of precipitate was
twice recrystallized from EtOAc–benzene mixture to
give ether 3, yield 0.33 g (10%), mp 137.5–138.5°C.
1Н NMR spectrum, δ, ppm: 4.42 d [4H, P(O)CH2,
2JPH = 5.5 Hz], 7.30–7.45 m (8H, m-CH ), 7.50–7.60 m
(4H, p-CH), 7.65–7.70 m (8H, o-CH). 31P NMR
spectrum: δP 27.7 ppm.
Dinutylphosphorylmethyl ester of p-toluene-
sulfonic acid (13) was prepared similarly to tosylate
12 from 1.7 g (8.7 mmol) of methanol 7, 3.3 g
(17.4 mmol) of TsCl, 4.8 g (34.8 mmol) of K2CO3, and
20 mL of acetone. The crude product (2.8 g, 93%) was
twice recrystallized from pentane–Et2O mixture to give
tosylate 13 as colorless crystalline solid; yield 2.1 g
(70%). Microanalysis and NMR data are given in
Tables 1 and 2.
Second portion of precipitate was twice recrys-
tallized from hexane–EtOAc mixture to give ether 5,
O-Alkylation of methanols 6 and 7 with tosylates
12 and 13 in the presence of Cs2CO3 (general
procedure). A mixture of 7.4 mmol of appropriate
methanol 6 or 7, 7.4 mmol of tosylate 12 or 13 and
14.8 mmol of Cs2CO3 in 15 mL of dioxane was
refluxed with stirring for 5 h. The mixture was diluted
with 15 mL of CHCl3 and 10 mL of H2O, the organic
layer was separated, successively washed with 5 mL of
H2O, 5 mL of diluted HCl (1 : 2), H2O (3 × 5 mL),
5 mL of saturated aqueous solution of NaHCO3, 5 mL
of H2O, dried over anhyd. Na2SO4 and concentrated in
vacuo.
1
yield 0.90 g (30%), mp 84.5–85.5°С. Н NMR spec-
3
trum, δ, ppm: 0.92 t (6H, Me, JHH = 7.2 Hz), 1.28–
1.70 m (12H, PCH2CH2CH2), 4.00 d (2H, BuPCH2,
2
2JPH = 6.6 Hz), 4.40 d (2H, PhPCH2, JPH = 5.3 Hz),
7.50–7.75 m (6H, m-CH + p-CH), 7.80–7.90 m (4H,
31
o-CH). P NMR spectrum, δP, ppm: 27.6 (PhP), 47.0
(BuP).
α-Dibutylphosphoryl-α'-diphenylphosphoryl di-
methyl ether (5). To a stirring solution of 0.71 g
(3.7 mmol) of methanol 7 in 10 mL dioxane 0.15 g
(3.7 mmol) of NaH (as 60% suspension in mineral oil)
was added, and the mixture was stirred at 20–25°С for
30 min, 1.42 g (3.7 mmol) tosylate 12 was then added
and mixture was refluxed with stirring for 5 h. The
reaction mixture was diluted with10 mL of CHCl3 and
5 mL of H2O, the organic layer was separated, washed
with H2O (3×5 mL), dried over anhyd. Na2SO4, and
concentrated in vacuo. The crude product (1.40 g,
93%) was three times recrystallized from a hexane-
EtOAc mixture to give ether 5 as colorless crystalline
solid, yield 0.95 g (63%). Microanalysis and NMR
data are given in Tables 1 and 2.
О-Alkylation of diphenylphosphorylmethanol 6
with tosylate 13. A mixture of 1.7 g (7.4 mmol) of
methanol 6, 2.6 g (7.4 mmol) of tosylate 13, and 4.8 g
(17.8 mmol) of Cs2CO3 in 15 mL of dioxane was
heated under the condition described in the general
procedure. According to 31P NMR data residue isolated
from organic layer contained 3% of ether 3 (δP
27.6 ppm), 94% of ether 5 (δP 27.9, 47.4 ppm), and 3%
of ether 4 (δP 46.7 ppm). The residue was four times
recrystallized from pentane–Et2O mixture to give ether
5 as colorless crystalline solid; yield 1.2 g (40%); mp
1
84.5–85.5°C. Н NMR spectrum, δ, ppm: 0.90 t (6H,
NMR spectroscopy studies were performed at
Center for Collective Usage, National Research Center
“Kurchatov Institute” and at Center for Study of
Molecules Structure, Nesmeyanov Institute of Organo-
element Compounds, RAS.
Me, 3JHH = 7.2 Hz), 1.30–1.70 m (12H, PCH2CH2CH2),
2
3.96 d (2H, BuPCH2, JPH = 6.6 Hz), 4.42 d (2H,
2
PhPCH2, JPH = 5.3 Hz), 7.50–7.70 m (6H, m-CH +
31
p-CH), 7.75–7.90 m (4H, o-CH). P{1H} NMR spec-
trum, δР, ppm: 27.6 (PhP), 46.9 (BuP).
CONFLICT OF INTERESTS
О-Alkylation of dibutylphosphorylmethanol 7
with tosylate 12. A mixture of 1.42 g (7.4 mmol) of
methanol 7, 2.86 g (7.4 mmol) of tosylate 12, and 4.82 g
(17.8 mmol) of Cs2CO3 in 5 mL of dioxane was heated
under the condition described in the general procedure.
According to 31P NMR data residue isolated from
organic layer contained 16% of ether 3 (δP 27.3 ppm),
68% of ether 5 (δP 27.5, 46.9 ppm), and 16% of ether 4
(δP 46.2 ppm). The residue was dissolved in 10 mL of
No conflict of interests was declared by the authors.
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