New chiral 1,4,2-oxazaphosphorinanes bearing a free hydroxy group

Article abstract of DOI:10.1007/s11172-021-3227-y

New chiral 3-aryl-2-hydroxy-2-oxo-5-R-1,4,2-oxazaphosphorinanes were obtained by a three-step one-pot synthesis, which included the preparation of imines from enantiopure (2R)-2-aminoalkan-1-ols, their phosphonylation and subsequent dealkylation of the P(

Full text of DOI:10.1007/s11172-021-3227-y

Russian Chemical Bulletin, International Edition, Vol. 70, No. 7, pp. 1383—1387, July, 2021
1383
New chiral 1,4,2-oxazaphosphorinanes bearing a free hydroxy group*
R. G. Zinnatullin, K. A. Nikitina, E. K. Badeeva, and K. E. Metlushka
Arbuzov Institute of Organic and Physical Chemistry,
Federal Research Center "Kazan Scientific Center of the Russian Academy of Sciences",
8 ul. Akad. Arbuzova, 420088 Kazan, Russian Federation.
Е-mail: metlushka@mail.ru
New chiral 3-aryl-2-hydroxy-2-oxo-5-R-1,4,2-oxazaphosphorinanes were obtained by
a three-step one-pot synthesis, which included the preparation of imines from enantiopure
(2R)-2-aminoalkan-1-ols, their phosphonylation and subsequent dealkylation of the
P(O)OEt-fragment. The major diastereomers of the compounds obtained were found to have
the (3R,5R)-configuration.
Key words: 1,4,2-oxazaphosphorinanes, triethyl phosphite, aromatic aldehydes, chiral
amino alcohols, phosphonates, amino phosphonic acids.
-Amino phosphonic acids, the isosteric analogs of
-amino carboxylic acids, are attracting close attention
of researchers. Currently, a large number of -amino
phosphonic acids and phosphono peptides based on them
is known, the compounds exhibiting antibacterial, antivi-
ral, antifungal, antitumor, and immunomodulatory activ-
ity.1—6 This family of compounds is mainly represented
by acyclic derivatives, while heterocycles containing
a phosphonic group are studied less. 1,4,2-Oxazaphos-
phorinanes represent a class of six-membered phosphorus-
containing heterocyclic compounds with the endocyclic
-amino phosphonic structural element.
Earlier, we have shown that 3-aryl-5-ethyl-1,4,2-oxaza-
phosphorinanes can be easily synthesized by a three-com-
ponent reaction of the imine derivative of 2-aminobutan-
1-ol, triethyl phosphite, and trifluoroacetic acid, followed
by treatment of the intermediately formed esters first with
bromotrimethylsilane and then with methanol (Scheme 1).7
This approach allows one to involve imines of hydroxy-
substituted benzaldehydes and to obtain final products
containing a hydroxy group in the aromatic substituent,
which is difficult to accomplish using other known meth-
ods for the synthesis of 1,4,2-oxazaphosphorinanes.8—13
In the present work, we expand this series of compounds
by using the imine prepared from salicylic aldehyde and
(R)-2-phenylglycinol (1a) as a reactant (Scheme 2). The
use of trifluoroacetic acid as a coelectrophile gave the
corresponding diastereomerically pure 1,4,2-oxazaphos-
phorinane 2a in 23% yield. Note that oxazaphosphorinane
synthesized earlier using (R)-2-(2-hydroxybenzyliden-
amino)butan-1-ol as a starting compound was isolated in
55% yield (see Scheme 1, Ar = 2-HOC6H4).7 Apparently,
the difference in the product yields can be explained by
the formation of large amounts of open-chain phosphonate
3a in the case of reactant 1a (see Scheme 2). In fact, the
31P NMR spectrum of the reaction mixture exhibits two
groups of signals with P = 13.2—14.9 (diastereomeric
cyclic phosphonates) and P = 16.51 and 16.96 (dia-
stereomeric open-chain phosphonates) with a ratio of peak
integral intensities equal to 2 : 1, respectively. We decided
to study the influence of the nature of the acid used in this
synthesis on the ratio of products. It turned out that the
use of trichloroacetic, monobromoacetic, or monochloro-
acetic acids instead of trifluoroacetic acid increases the
ratio of cyclic and open-chain phosphonates from 3 : 1 to
8 : 1 (see Scheme 2).
Scheme 1
Ar = Ph, 2-HOC6H4, 3-HOC6H4
The overall yield of products can be significantly in-
creased if to use the starting imine 1a as obtained in situ,
without its isolation in the pure form. It was also possible
to finally remove the ethyl group upon treatment with
Me3SiBr and MeOH in the same reaction vessel. Thus,
all the synthetic steps were successfully carried out as
Reagents and conditions: 1) P(OEt)3, CF3COOH/CH2Cl2;
2) Me3SiBr/CH2Cl2; 3) MeOH.
* Based on the materials of the II Scientific Conference "Dynamic
Processes in the Chemistry of Organoelement Compounds"
(November 11—13, 2020, Kazan, Russia).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp. 1383—1387, July, 2021.
1066-5285/21/7007-1383 © 2021 Springer Science+Business Media LLC

Zinnatullin et al.
1384
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 7, July, 2021
Scheme 2
on the nature of the starting compounds (the reaction
progress was monitored by TLC).
The major diastereomers of 3,5-disubstituted 1,4,2-ox-
azaphosphorinanes 4a—h were isolated in 45—69% over-
all yield. Unfortunately, the new compounds 4a—d,f—h
precipitated from the reaction mixtures as fine-crystalline
powders not suitable for X-ray diffraction studies. The
configuration of the chiral centers in the products was
established by 1H NMR spectroscopy. In fact, the vicinal
spin-spin coupling constants, which correlate with the
dihedral angles, can provide clear information on the
mutual arrangement of substituents (cis or trans) at the
atoms C(3) and C(5), i.e., on the configuration of chiral
centers in the "rigid" cyclic molecules under discussion.
It was shown14 that in the 1H NMR spectra (recorded in
acetone-d6 and CDCl3) of 2-R-2-oxo-3,5-diphenyl-1,4,2-
oxazaphosphorinanes (R = H or Ar) with the same relative
configuration of the atoms C(3) and C(5) structurally
similar to the studied objects, the constants 3JP,H (6) and
ax
3JP,H
are 2.1—3.6 Hz and 18.6—21.5 Hz, while the
Reagents and conditions: 1) P(OEt)3, RCO2H, CH2Cl2;
2) 020 C.
(6)
consteaqnts 3JH
and 3JH
are equal to
(5),H (6)
ax
(5),H (6)
10.5—10.9 Hzaaxnd 2.1—3.3 Hz, respectievqely. For 5-ethyl-
2-hydroxy-3-(2-hydroxyphenyl)-2-oxo-1,4,2-oxazaphos-
phorinane (R,R)-4e we obtained earlier (Fig. 1), the
ax
RCO2H
CF3CO2H
CCl3CO2H
2a : 3a
2 : 1
3 : 1
RCO2H
BrCH2CO2H
ClCH2CO2H
2a : 3a
6 : 1
8 : 1
3
3
constants JP,H
and JP,H
are 2.8 and 18.0 Hz,
(6) are 11.1 and 3.2 Hz
(6)
(6)
ax
eq
(5),H
while 3JH
(6) and 3JH
ax
(5),H
(the spectrum was recorded in D2eOq with the addition of
K2CO3 to increase solubility).7
ax
ax
a one-pot process. We involved in this process salicylic,
3-methoxysalicylic, 3,5-dibromosalicylic, and 5-nitro-
salicylic aldehydes, as well as (R)-2-aminobutan-1-ol and
(R)-2-phenylglycinol as the starting compounds and ob-
tained imines 1a—h (Scheme 3). 1,2-Dichloroethane was
chosen as the solvent instead of the dichloromethane used
earlier,7 which allowed us to carry out the step of imine
preparation at a higher temperature for 1—5 h, depending
a
N(4)
C(3)
C(5)
Scheme 3
O(1)
P(2)
C(6)
b
1, 2, 4
R
Ph
Ar
1, 2, 4
e
f
g
h
R
Et
Ar
a
b
c
d
2-HOC6H4
2-HOC6H4
Ph 2-HO-3-MeOC6H3
Ph 2-HO-3,5-Br2C6H2
Ph 2-HO-5-O2NC6H3
Et 2-HO-3-MeOC6H3
Et 2-HO-3,5-Br2C6H2
Et 2-HO-5-O2NC6H3
Fig. 1. Molecular structure of compound (R,R)-4e (a) and some
Reagents and conditions: i. MgSO4, ClCH2CH2Cl, ; ii. P(OEt)3,
ClCH2CO2H, 020 C; iii. Me3SiBr, 020 C; iv. MeOH.
spin-spin coupling constants (b): 3JH
= 3.2 Hz,
(5),H (6)
3JH
(6) = 11.1 Hz, 3JP,H (6) = 18.0 aHx z, 3JPeq,H (6) = 2.8 Hz.
(5),H
ax ax
eq
ax

1,4,2-Oxazaphosphorinanes
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 7, July, 2021
1385
Table 1. Chemical shifts H(6) and characteristic spin-spin coupling constant in the 1H NMR
spectra of 1,4,2-oxazaphosphorinanes 4a—h*
Com-
pound

J/Hz
H
ax(6)
Heq(6)
3JH
3JH
3JP,H
3JP,H
(6)
eq
(5),H (6)
ax
(5),H (6)
eq
(6)
ax
ax
ax
4a
4b
4c
4d
4e
4f
4.42
4.43
4.39
4.45
4.09
4.08
4.09
4.07
4.18
4.19
4.19
4.24
4.18
4.18
4.17
4.18
11.3
11.1
11.5
10.9
11.1
11.0
11.4
11.5
3.0
2.8
2.8
2.9
3.2
3.2
2.9
2.7
2.6
18.4
18.5
17.9
17.6
18.0
17.8
18.3
18.1
2.6
2.6
2.4
2.8
3.1
2.9
2.5
4g
4h
* The spectra were recorded in D2O with the addition of 5 equiv. of K2CO3.
the wavelength range from 4000 to 400 cm–1 with an optical
resolution of 4 cm–1 ( denotes stretching vibrations,  denotes
bending vibrations). Electrospray ionization (ESI) mass spectra
were obtained on a Bruker AmazonX mass spectrometer with an
ion trap. The measurements were carried out in the positive ion
mode in the m/z range from 70 to 3000. The nebulizer capillary
voltage was –3500 V. Nitrogen with a temperature of 250 C and
a flow rate of 10 L min–1 was used as a drying gas. The analyzed
sample was dissolved in distilled water to a concentration of
~10–3 mg mL–1 with the addition of 5 equiv. (relative to
the sample) of K2CO3. Elemental analysis was performed on
a EuroEA3028-HT-OM analyzer (Eurovector SpA). Optical
rotation was measured on a Perkin Elmer polarimeter (model 341)
Thus, if the major diastereomers of compounds
4a—d,f—h have the same relative configuration of the
chiral centers, then it can be expected that the spin-spin
coupling constants between the nuclei P(1) and H(6), as
well as H(5) and H(6) should be close to the values
we gave earlier. In fact, it was shown that the con-
3
3
stants JP,H
and JP,H
for oxazaphosphorinanes
(6)
(6)
ax
eq
4a—d,f—h are 2.4—3.1 Hz and 17.6—18.5 Hz, while the
3
constants 3JH
and JH
are equal to
(5),H (6)
eq
(5),H (6)
ax
ax
ax
10.9—11.5 and 2.7—3.2 Hz, respectively (Table 1). The
established fact allows us to state that all the isolated by
crystallization 3-aryl-2-hydroxy-2-oxo-5-R-1,4,2-oxaza-
phosphorinanes 4a—h are diastereomers with cis-arrange-
ment of substituents at the atoms C(3) and C(5), i.e., have
the same (R,R)-configuration of the chiral atoms, taking
into account the configuration of the chiral center in the
starting amino alcohols used.
at 20 C (the molar ratio of oxazaphosphorinane : K2CO3
=
= 1 : 5). Melting points were determined on a BOETIUS melt-
ing point microscope.
The following commercially available reagents were used in
the work: salicylic aldehyde (99%, Acros Organics), 3-meth-
oxysalicylic aldehyde (99%, Alfa Aesar), 3,5-dibromosalicylic
aldehyde (98%, Acros Organics), 5-nitrosalicylic aldehyde (98%,
Alfa Aesar), (R)-(–)-2-aminobutan-1-ol (98%, Acros Organics),
(R)-(–)-2-phenylglycinol (98%, Acros Organics), triethyl phos-
phite (98%, Sigma-Aldrich), monochloroacetic acid (99%, J&K
Scientific), bromotrimethylsilane (97%, J&K Scientific).
(R)-2-(2-Hydroxybenzylidenamino)-2-phenylethanol (1a) was
obtained by the reaction of salicylic aldehyde (1.22 g, 10 mmol)
and (R)-2-phenylglycinol (1.37 g, 10 mmol) in benzene (10 mL).
The reaction mixture was refluxed for 4 h with a Dean—Stark
trap, then concentrated. The residue was recrystallized from ethyl
acetate—hexane solvent mixture (3.5 mL and 8.5 mL, respec-
tively). The crystals formed were collected by filtration and dried
in vacuo of a water-jet pump. The yield was 1.8 g (75%), m.p.
In conclusion, we used a sequence of reactions includ-
ing preparation of imines, their phosphonylation and
dealkylation of the resulting esters without isolation of the
intermediate products to synthesize a series of new
1,4,2-oxazaphosphorinanes, potential biologically active
compounds containing an aryl substituent bearing a hydr-
oxy group at position 3 of the ring. Using 1H NMR spec-
troscopy, it was shown that the major diastereomers of the
oxazaphosphorinanes obtained have the same relative
configuration of the chiral centers.
Experimental
20
89—90 C (Ref. 15: 87—88 C), []D = +172.5 (c 1, CHCl3)
(Ref. 16: []D25 = +118 (c 0.4, CHCl3)). Found (%): C, 74.58;
H, 6.38; N, 6.02. C15H15NO2. Calculated (%): C, 74.67; H, 6.27;
N, 5.81. 1H NMR (DMSO-d6), : 3.64—3.74 (m, 2 H, CH2OH);
4.45 (dd, 1 H, CHPh, 3JH,H = 8.7 Hz, 3JH,H = 4.4 Hz); 5.05 (br.
dd, 1 H, CH2OH, 3JH,H = 5.8 Hz, 3JH,H = 5.5 Hz); 6.86—6.92
(m, 2 H, CaromH); 7.28—7.49 (m, 7 H, CaromH); 8.61 (s, 1 Н,
1H NMR spectra were recorded on a Bruker AVANCE-600
spectrometer (600.13 MHz) using the signals of the residual
proton of the deuterated solvent (D2O) as a reference for
chemical shifts, 31Р NMR spectra were recorded on a Bruker
AVANCE-600 spectrometer (242.94 MHz) using 85% aqueous
H3PO4 as an external standard. The sample solutions for NMR
spectroscopy were prepared with the addition of potassium car-
bonate to increase solubility (the molar ratio of oxazaphospho-
rinane : K2CO3 = 1 : 5). IR spectra were recorded on Bruker
Tensor 27 and Bruker Vector 22 spectrometers in KBr pellets in
CH=N); 13.54 (s, 1 Н, C6H4OH). IR (KBr, Vector 22), /cm–1
:
1626 (C=N), 1579 (C···C), 1274 (CH2), 1212 (Ph—ОН),
1044 (ОН).
Test reactions of (R)-2-(2-hydroxybenzylidenamino)-2-phen-
ylethanol (1a) with triethyl phosphite in the presence of haloacetic

Zinnatullin et al.
1386
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 7, July, 2021
acids. Imine 1a (0.12 g, 0.5 mmol) was placed in a flask to-
gether with dichloromethane (2 mL), and the reaction mixture
was cooled in a bath (ice with salt). Then, a solution of triethyl
phosphite (0.09 g, 0.55 mmol) in dichloromethane (1 mL) was
added with stirring, and after 10 min haloacetic acid was added
dropwise: trifluoroacetic acid (84 μL, 1.1 mmol in dichlorometh-
ane (0.5 mL)), trichloroacetic acid (0.18 g, 1.1 mmol), mono-
bromoacetic acid (0.15 g, 1.1 mmol), monochloroacetic acid
(0.1 g, 1.1 mmol). The resulting reaction mixtures were stirred
for 24 h and then analyzed by 31Р NMR spectroscopy.
Synthesis of 3,5-disubstituted 2-hydroxy-2-oxo-1,4,2-oxaza-
phosphorinanes 4a—h (procedures A and B). Salicylic aldehyde,
3-methoxysalicylic aldehyde, 5-nitrosalicylic aldehyde (6.9 mmol
(A)), 3,5-dibromosalicylic aldehyde (3.4 mmol (B)), as well as
(R)-(–)-2-aminobutan-1-ol (6.9 mmol (A) or 3.4 mmol (B)) or
(R)-(–)-2-phenylglycinol (6.9 mmol (A) or 3.4 mmol (B)) were
placed in flasks together with 1,2-dichloroethane (10 mL) and
anhydrous magnesium sulfate (6.9 mmol (A) or 3.4 mmol (B)).
The resulting mixtures were refluxed for 1—5 h (the reaction
progress was monitored by TLC). The cooled mixtures were
placed in cooling baths (ice with salt), followed by the addition
of a solution of triethyl phosphite (7.59 mmol (A) or 3.74 mmol
(B)) in 1,2-dichloroethane (5 mL) (A and B) with stirring, after
10 min monochloroacetic acid (15.18 mmol (A) or 7.48 mmol
(B)) was added. The resulting suspensions were stirred for 24 h,
then heated, the drying agent was filtered off and washed with
1,2-dichloroethane (2 mL) (A, B). The reaction mixtures were
allowed to cool, placed in cooling baths (ice with salt), and
a solution of bromotrimethylsilane (20.7 mmol (A) or 10.2 mmol
(B)) in 1,2-dichloroethane (8 mL) (A, B) was added with stirring.
The resulting reaction mixtures were stirred for 1 h with cooling,
kept at room temperature for 48 h, and concentrated.
C, 57.31; H, 5.41; N, 4.18; P, 9.24. 1H NMR (D2O with K2CO3),
: 3.82 (s, 3 H, OCH3); 4.19 (ddd, 1 H, C(6)Heq, 3JP,H = 18.5 Hz,
3
2JH,H = 11.7 Hz, JH,H = 2.8 Hz); 4.30 (dd, 1 H, C(5)H,
3
3JH,H = 11.1 Hz, JH,H = 2.8 Hz); 4.43 (ddd, 1 H, C(6)Hax
,
2JH,H = 11.7 Hz, 3JH,H = 11.1 Hz, 3JP,H = 2.6 Hz); 4.54 (d, 1 H,
C(3)H, 2JP,H = 12.9 Hz); 6.80—7.02 (m, 3 H, CaromH); 7.36—7.47
(m, 5 H, CaromH). 31P NMR (D2O with K2CO3), P: 13.02. IR
(KBr, Vector 22), /cm–1: 1610, 1593 (C···C), 1456 (CH2), 1225
(PO2), 1199 (Ph—ОН), 1038 (PO—C), 757 (P—C). MS
(ESI+), m/z (Irel (%)): 374.0 [M + K]+ (100), 336.1 [M + H]+ (24).
(R,R)-2-Hydroxy-3-(2-hydroxy-3,5-dibromophenyl)-2-oxo-
5-phenyl-1,4,2-oxazaphosphorinane (4c). The residue formed
after evaporation was dissolved in methanol (8 mL) and kept at
room temperature for 4 h, then allowed to stand at –15 C for
48 h. The precipitate formed was collected by filtration and dried
in vacuo of an oil pump. The yield was 1.05 g (67%), m.p.
248—250 C, []D20 = –37 (c 0.25, H2O with K2CO3). Found (%):
C, 38.65; H, 3.07; Br, 34.22; N, 3.21; P, 6.70. C15H14Br2NO4P.
Calculated (%): C, 38.91; H, 3.05; Br, 34.51; N, 3.02; P, 6.69.
1H NMR (D2O with K2CO3), : 4.19 (ddd, 1 H, C(6)Heq
,
3JP,H = 17.9 Hz, 2JH,H = 11.5 Hz, 3JH,H = 2.8 Hz); 4.30 (dd, 1 H,
3
3
C(5)H, JH,H = 11.0 Hz, JH,H = 2.8 Hz); 4.39 (br.ddd, 1 H,
3
3
C(6)Hax
,
2JH,H = 11.5 Hz, JH,H = 11.5 Hz, JP,H = 2.6 Hz);
2
4.76 (d, 1 H, C(3)H, JP,H = 13.5 Hz); 7.32—7.45 (m, 5 H;
CaromH); 7.51 (br.s, 1 H, CaromH); 7.57 (br.s, 1 H, CaromH).
31P NMR (D2O with K2CO3), P: 13.94. IR (KBr, Tensor 27),
/cm–1: 1617, 1586 (C···C), 1464 (CH2), 1232 (PO2), 1201
(Ph—ОН), 1038 (PO—C), 756 (P—C). MS (ESI+), m/z
(Irel (%)): 501.8 [M + K]+ (100), 463.9 [M + H]+ (90).
(R,R)-2-Hydroxy-3-(2-hydroxy-3-nitrophenyl)-2-oxo-5-
phenyl-1,4,2-oxazaphosphorinane (4d). The residue formed after
evaporation was dissolved in methanol (10 mL) and kept at room
temperature for 4 h. After addition of propan-2-ol (10 mL), the
resulting solution was allowed to stand at –15 C for 48 h. The
precipitate formed was collected by filtration and dried in vacuo
of an oil pump. The yield was 1.54 g (64%), m.p. 283—284 C,
[]D20 = +156 (c 0.25, H2O with K2CO3). Found (%): C, 51.66;
H, 4.59; N, 7.83; P, 9.11. C15H15N2O6P. Calculated (%):
C, 51.44; H, 4.32; N, 8.00; P, 8.84. 1H NMR (D2O with K2CO3),
(R,R)-2-Hydroxy-3-(2-hydroxyphenyl)-2-oxo-5-phenyl-1,4,2-
oxazaphosphorinane (4a). The residue formed after evaporation
was dissolved in methanol (10 mL) and kept at room temperature
for 4 h, then again concentrated, and the resulting viscous mass
was dissolved in propan-2-ol (8 mL). The resulting solution was
allowed to stand at –15 C for 48 h. The precipitate formed was
collected by filtration and dried in vacuo of an oil pump. The
yield was 1.2 g (57%), m.p. 244—247 C, []D20 = –14 (c 0.25,
H2O with K2CO3). Found (%): C, 59.30; H, 5.57; N, 4.82;
P, 9.96. C15H16NO4P. Calculated (%): C, 59.02; H, 5.28; N, 4.59;
P, 10.15. 1H NMR (D2O with K2CO3), : 4.18 (ddd, 1 H,
3
2
: 4.24 (ddd, 1 H, C(6)Heq, JP,H = 17.6 Hz, JH,H = 11.7 Hz,
3JH,H = 2.9 Hz); 4.32 (dd, 1 H, C(5)H, JH,H = 10.9 Hz,
3
3JH,H = 2.9 Hz); 4.45 (ddd, 1 H, C(6)Hax
,
2JH,H = 11.7 Hz,
3JH,H = 10.9 Hz, JP,H = 2.4 Hz); 4.66 (d, 1 H, C(3)H,
3
2
3
3
C(6)Heq
,
3JP,H = 18.4 Hz, JH,H = 11.8 Hz, JH,H = 3.0 Hz);
2JP,H = 11.9 Hz); 6.52 (d, 1 H, CaromH, JH,H = 9.5 Hz);
3
3
4.30 (dd, 1 H, C(5)H, JH,H = 11.3 Hz, JH,H = 3.0 Hz); 4.42
7.35—7.47 (m, 5 H, CaromH); 7.99 (dd, 1 H, CaromH,
3
4
(ddd, 1 H, C(6)Hax
,
2JH,H = 11.8 Hz, JH,H = 11.3 Hz,
3JH,H = 9.5 Hz, JH,H = 2.6 Hz); 8.49 (br.s, 1 H, CaromH).
3JP,H = 2.6 Hz); 4.52 (d, 1 H, C(3)H, 2JP,H = 12.8 Hz); 6.82—6.87
(m, 2 H, CaromH); 7.19—7.48 (m, 7 H, CaromH). 31P NMR (D2O
with K2CO3), P: 14.09. IR (KBr, Vector 22), /cm–1: 1619,
1603 (C···C), 1457 (CH2), 1228 (PO2), 1210 (Ph—ОН), 1041
(PO—C), 755 (P—C). MS (ESI+), m/z (Irel (%)): 344.1
[M + K]+ (55), 306.2 [M + H]+ (100).
31P NMR (D2O with K2CO3), P: 13.58. IR (KBr, Vector 22),
/cm–1: 1617, 1592 (C···C), 1528 (asC—NO2), 1440 (CH2),
1346 (sC—NO2), 1232 (PO2), 1210 (Ph—ОН), 1038 (PO—C),
749 (P—C). MS (ESI+), m/z (Irel (%)): 389.0 [M + K]+ (100),
351.1 [M + H]+ (78).
(R,R)-5-Ethyl-2-hydroxy-3-(2-hydroxyphenyl)-2-oxo-1,4,2-
oxazaphosphorinane (4e). The residue formed after evaporation
was dissolved in methanol (6 mL) and kept at room temperature
for 4 h, followed by the addition of propan-2-ol (6 mL). The
resulting solution was allowed to stand with cooling (–15 C) for
48 h. The precipitate formed was collected by filtration and dried
in vacuo of an oil pump. The product (1.1 g, 55%) was obtained
as a solvate with methanol. Physical characteristics agree with
those described earlier.7
(R,R)-2-Hydroxy-3-(2-hydroxy-3-methoxyphenyl)-2-oxo-
5-phenyl-1,4,2-oxazaphosphorinane (4b). The residue formed
after evaporation was dissolved in methanol (10 mL) and kept at
room temperature for 4 h, then again concentrated, and the
resulting viscous mass was dissolved in 96% aqueous ethanol
(8 mL). The resulting solution was allowed to stand at –15 C
for 48 h. The precipitate formed was collected by filtration and
dried in vacuo of an oil pump. The yield was 1.59 g (69%), m.p.
254—256 C, []D20 = –20 (c 0.25, H2O with K2CO3). Found (%):
C, 57.14; H, 5.28; N, 4.28; P, 9.37. C16H18NO5P. Calculated (%):
(R,R)-5-Ethyl-2-hydroxy-3-(2-hydroxy-3-methoxyphenyl)-
2-oxo-1,4,2-oxazaphosphorinane (4f). The residue formed after

1,4,2-Oxazaphosphorinanes
Russ. Chem. Bull., Int. Ed., Vol. 70, No. 7, July, 2021
1387
evaporation was dissolved in methanol (6 mL) and kept at room
temperature for 4 h. This was again concentrated, and the result-
ing viscous mass was dissolved in propan-2-ol (8 mL). The result-
ing solution was allowed to stand with cooling (+5 C) for 48 h.
The precipitate formed was collected by filtration and dried
in vacuo of an oil pump. The yield was 0.85 g (45%), m.p.
269—270 C, []D20 = –7 (c 0.25, H2O with K2CO3). Found (%):
C, 50.34; H, 6.50; N, 4.78; P, 10.51. C12H18NO5P. Calculat-
ed (%): C, 50.18; H, 6.32; N, 4.88; P, 10.78. 1H NMR (D2O
The authors gratefully acknowledge the Spectral-
Analytical Center of Shared Facilities for Study of Struc-
ture, Composition and Properties of Substances and
Materials of Federal Research Center of Kazan Scientific
Center of the Russian Academy of Sciences for providing
necessary facilities to carry out this work.
This paper does not contain descriptions of studies on
animals or humans.
3
with K2CO3), : 0.91 (t, 3 H, CH2CH3, JH,H = 7.5 Hz);
The authors declare no competing interests.
1.38—1.45 (m, 2 H, CH2CH3); 3.00—3.07 (m, 1 H, C(5)H);
3.81 (s, 3 H, OCH33); 4.08 (ddd, 1 H, C(6)Hax, 2JH,H = 11.5 Hz,
References
3JH,H = 11.0 Hz, JP,H = 3.1 Hz); 4.18 (ddd, 1 H, C(6)Heq
,
3JP,H = 17.8 Hz, 2JH,H = 11.5 Hz, 3JH,H = 3.2 Hz); 4.36 (d, 1 H,
C(3)H, 2JP,H = 13.2 Hz); 6.77—6.99 (m, 3 H, CaromH). 31P NMR
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(D2O with K2CO3), P: 13.84. IR (KBr, Vector 22), /cm–1
:
1609, 1593 (C···C), 1487 (CH2), 1251 (PO2), 1209 (Ph—ОН),
1050 (PO—C), 781 (CH2(Et)), 740 (P—C). MS (ESI+), m/z
(Irel (%)): 326.0 [M + K]+ (100), 288.1 [M + H]+ (46).
(R,R)-5-Ethyl-2-hydroxy-3-(2-hydroxy-3,5-dibromophenyl)-
2-oxo-1,4,2-oxazaphosphorinane (4g). The residue formed after
evaporation was dissolved in methanol (6 mL) and kept at room
temperature for 4 h. Propan-2-ol (6 mL) was added, and the
resulting solution was allowed to stand at –15 C for 48 h. The
precipitate formed was collected by filtration and dried in vacuo
of an oil pump. The yield was 0.86 g (61%), m.p. 279—280 C,
20
[]D = –3 (c 0.25, H2O with K2CO3). Found (%): C, 31.72;
H, 3.14; Br, 38.34; N, 3.61; P, 7.18. C11H14Br2NO4P. Calculat-
ed (%): C, 31.83; H, 3.40; Br, 38.51; N, 3.37; P, 7.46. 1H NMR
(D2O with K2CO3), : 0.93 (t, 3 H, CH2CH3, 3JH,H = 7.6 Hz);
1.39—1.46 (m, 2 H, CH2CH3); 3.07—3.13 (m, 1 H, C(5)H);
4.09 (br.ddd, 1 H, С(6)Hax, 2JH,H = 11.4 Hz, 3JH,H = 11.4 Hz,
3JP,H = 2.9 Hz); 4.17 (ddd, 1 H, C(6)Heq 3JP,H = 18.3 Hz,
,
2JH,H = 11.4 Hz, 3JH,H = 2.9 Hz); 4.46 (d, 1 H, C(3)H, 2JP,H
=
9. V. A. Alfonsov, Ch. E. McKenna, E. V. Bayandina, B. A.
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6<529::AID-CHIR41>3.0.CO;2-3.
= 13.3 Hz); 7.48 (br.s, 1 H, CaromH); 7.59 (br.s, 1 H, CaromH).
31P NMR (D2O with K2CO3), P: 14.21. IR (KBr, Tensor 27),
/cm–1: 1610 (C···C), 1464 (CH2), 1235 (PO2), 1212 (Ph—ОН),
1045 (PO—C), 769 (CH2(Et)), 731 (P—C). MS (ESI+), m/z
(Irel (%)): 453.8 [M + K]+ (100), 415.9 [M + H]+ (75).
(R,R)-5-Ethyl-2-hydroxy-3-(2-hydroxy-5-nitrophenyl)-2-
oxo-1,4,2-oxazaphosphorinane (4h). The residue formed after
evaporation was dissolved in methanol (10 mL) and kept at room
temperature for 4 h. This was again concentrated, and the result-
ing viscous mass was dissolved in 96% aqueous ethanol (7 mL).
The resulting solution was allowed to stand at –15 C for 48 h.
The precipitate formed was collected by filtration and dried
in vacuo of an oil pump. The yield was 1.08 g (52%), m.p.
20
274—275 C, []D = +15 (c 0.25, H2O with K2CO3). Found (%):
C, 43.46; H, 5.19; N, 9.18; P, 10.13. C11H15N2O6P. Calculat-
ed (%): C, 43.72; H, 5.00; N, 9.27; P, 10.25. 1H NMR (D2O
3
with K2CO3), : 0.89 (t, 3 H, CH2CH3, JH,H = 7.7 Hz);
1.35—1.42 (m, 2 H, CH2CH3); 2.99—3.05 (m, 1 H, C(5)H);
4.07 (br.ddd, 1 H, С(6)Hax, 2JH,H = 11.5 Hz, 3JH,H = 11.5 Hz,
3JP,H = 2.5 Hz); 4.18 (ddd, 1 H, С(6)Heq
,
3JP,H = 18.1 Hz,
3
2JH,H = 11.5 Hz, JH,H = 2.7 Hz); 4.43 (d, 1 H, C(3)H,
16. M. Enamullah, J. Coord. Chem., 2012, 65, 911; DOI: 10.1080/
00958972.2012.664639.
3
2JP,H = 12.1 Hz); 6.51 (d, 1 H, CaromH, JH,H = 9.5 Hz); 7.97
3
4
(dd, 1 H, CaromH, JH,H = 9.5 Hz, JH,H = 2.3 Hz); 8.39 (br.s,
1 H, CaromH). 31P NMR (D2O with K2CO3), P: 15.00. IR (KBr,
Vector 22), /cm–1: 1619, 1594 (C···C), 1535 (asC—NO2), 1448
(CH2), 1346 (sC—NO2), 1231 (PO2), 1209 (Ph—ОН), 1041
(PO—C), 772 (CH2(Et)), 753 (P—C). MS (ESI+), m/z
(Irel (%)): 341.0 [M + K]+ (100), 303.1 [M + H]+ (62).
Received January 14, 2021;
in revised form February 11, 2021;
accepted February 15, 2021