Chemoselective Cross-Coupling of Secondary Phosphine Chalcogenides with Aminophenols: Synthesis of Aminophenylchalcogenophosphinic Acids O-Esters

Article abstract of DOI:10.1134/S1070363218100341

Chemoselective reaction of secondary phosphine chalcogenides with 2-aminophenol under mild conditions (room temperature, 2–4 h, CCl₄–Et₃N) led to the formation of aminophenylchalcogenophosphinic acids O-esters in a yield of up to 80%

Full text of DOI:10.1134/S1070363218100341

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 10, pp. 2223–2226. © Pleiades Publishing, Ltd., 2018.
Original Russian Text © K.O. Khrapova, P.A. Volkov, N.I. Ivanova, A.A. Telezhkin, N.K. Gusarova, B.A. Trofimov, 2018, published in Zhurnal Obshchei
Khimii, 2018, Vol. 88, No. 10, pp. 1739–1742.
LETTERS
TO THE EDITOR
Chemoselective Cross-Coupling of Secondary Phosphine
Chalcogenides with Aminophenols:
Synthesis of Aminophenylchalcogenophosphinic Acids O-Esters
K. O. Khrapovaa, P. A. Volkova, N. I. Ivanovaa,
A. A. Telezhkina, N. K. Gusarovaa, and B. A. Trofimova*
a A.E. Favorskii Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
*e-mail: boris_trofimov@irioch.irk.ru
Received July 5, 2018
Abstract—Chemoselective reaction of secondary phosphine chalcogenides with 2-aminophenol under mild
conditions (room temperature, 2–4 h, CCl4–Et3N) led to the formation of aminophenylchalcogenophosphinic
acids O-esters in a yield of up to 80%.
Keywords: secondary phosphine chalcogenides, aminophenols, chemoselective oxidative cross-coupling
DOI: 10.1134/S1070363218100341
Oxidative cross-coupling reactions of secondary
phosphine chalcogenides with NH-, OH- and SH-
compounds in the presence of an oxidizing agent
(CCl4) [1] is a convenient approach to the synthesis of
amides [2–4], esters [5] and thioesters [6] of chalco-
genophosphinic acids, precursors of drugs [7–11],
ligands for metal complex catalysts of a new genera-
tion [12–14], and intermediates for the production of
modern innovative materials [15–17]. One of the
promising areas of development of these reactions is
the study of their chemoselectivity in the presence of
two or more competing protogenic sites. Typically
these are multifunctional compounds containing
several HN, HO, and HS groups in various combina-
tions. These studies open the way to new promising
derivatives of phosphinic acids.
The purpose of this work was to study the reaction
of secondary phosphine chalcogenides with amino-
phenols in the CCl4–Et3N system. We have previously
found that phenol [5] and aniline [4] react with
secondary phosphine selenides under mild conditions
(room temperature, 1 h, CCl4–Et3N) to form ester 1 or
amide 2 of selenophosphinic acid, respectively, in a
yield of 86–87% (Scheme 1). Chloroform and triethyl-
ammonium hydrochloride were also identified in the
reaction mixtures.
Using available (obtained from red phosphorus and
styrene [18]) bis(2-phenylethyl)phosphine oxide 3a,
phosphine sulfide 3b and phosphine selenide 3c, as
well as 2-aminophenol 4, we showed for the first time
that the oxidative cross-coupling of secondary phos-
Scheme 1.
OH
NH2
Se
Se
Ph
Ph
Ph
Se
P
Ph
Ph
P
P
+ CCl4 + Et3N
O
Ph
NH
20_25oC,
1 h
20_25oC,
1 h
H
2 (86%)
1 (87%)
2223

2224
KHRAPOVA et al.
Scheme 2.
HO
X
O
X
Et3N_CCl4
Ph
Ph
Ph
Ph
+
P
P
_CHCl3
_[Et3NH]Cl
H
H2N
H2N
5а_5c (59_80%)
3а−3c
X = O, S, Se.
phine chalcogenides with aminophenols occurred in
CCl4–Et3N system at room temperature in 2–4 h with
the chemoselective formation of O-esters of amino-
phenylchalcogenophosphinic acids 5a–5c in 59–80%
yield (Scheme 2).
hydroxyl substituent and the nitrogen atom in 2-amino-
phenol [21], which greatly reduces the basicity (and
nucleophilicity) of the amino group.
In summary, the oxidative cross-coupling of
secondary phosphine chalcogenides with aminophenols
easily proceeds under mild conditions (room tem-
perature, 2–4 h, CCl4–Et3N system) with the chemo-
selective formation of O-esters of aminophenylchalco-
genophosphinic acids.
Full conversion of secondary phosphine chalco-
genides 3a–3c was achieved in 4, 3, and 2 h,
respectively, i.e., their reactivity increases in the series:
phosphine oxide 3a < phosphine sulfide 3b <
phosphine selenide 3c, which is consistent with known
data [19]. As side compounds in these processes the
corresponding bis(2-phenylethyl)phosphinic, -thiophos-
phinic and -selenophosphinic acid anhydrides were
formed (detected by 31P NMR using authentic samples
as reference [20]). In addition, preliminary results were
obtained (to be published later) that the reaction
between bis(2-phenylethyl)phosphine selenide and
3-aminophenol proceeded under similar conditions
(20–25°С, 7 h, CCl4–Et3N) also to form chemoselec-
tively O-(3-aminophenyl) bis(2-phenylethyl)phosphino-
selenoate.
The reactions were carried out in an inert atmo-
sphere (argon). The reaction progress was monitored
by 31P NMR method.
Cross-coupling reactions of secondary phos-
phine chalcogenides 3a–3c with 2-aminophenol 4.
To a solution of the secondary phosphine chalcogenide
3a–3c (1.0 mmol) in a mixture of CCl4 (3 mL) and 1,4-
dioxane (1 mL) was added Et3N (1.0 mmol). The
resulting mixture was stirred at 20–25°C for 10 min,
then 2-aminophenol 4 (1.0 mmol) was added and
stirring continued at room temperature (20–25°C) for
2–4 h. The solvent was evaporated at a reduced
pressure, 1,4-dioxane (3 mL) was added to the residue.
The precipitate (triethylammonium hydrochloride) was
removed by filtration, the filtrate was evaporated. The
viscous residue was washed with hexane (7 × 2 mL)
and dried at a reduced pressure.
The plausible mechanism of oxidative cross-
coupling involves the formation of halide A in the first
stage [4], which then reacts with 2-aminophenol
chemoselectively involving of the hydroxyl group of
the latter (Scheme 3).
2-Aminophenyl bis(2-phenylethyl)phosphinate (5a).
Yield 219 mg (60%), viscous liquid. 1Н NMR
spectrum (CDCl3), δ, ppm: 1.87–2.00 m (4Н, СН2Р),
The almost complete inactivity of the amino group
in this process can apparently be ascribed to the well-
known existence of a hydrogen bond between the
Scheme 3.
H2N
, Et3N
X
O
X
X
Ph
Ph
Ph
Ph
Ph
Ph
CCl4
HO
P
P
P
_CHCl3
_[Et3NH]Cl
H
Cl
3
A
5
H2N
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 10 2018

CHEMOSELECTIVE CROSS-COUPLING OF SECONDARY PHOSPHINE CHALCOGENIDES
2225
2.80–2.92 m (4Н, PhСН2), 6.71–7.01 m (3Н, H3–5
,
meters (400.13, 100.62, 40.56, 161.98, and 76.31 MHz,
OPh), 7.09–7.11 m, 7.14–7.16 m and 7.19–7.21 m
respectively) using HMDS (1H, 13C), MeNO2 (15N),
Me2Se (77Se) as internal reference and 85% H3PO4
(31P) as external reference. The signal assignment in
(11Н, Ph + H6, OPh). 13C NMR spectrum (CDCl3), δC,
1
ppm: 28.4 (PhСН2), 31.5 d (СН2Р, JPС = 89.5 Hz),
116.9 (C3, OPh), 119.6 (C5, OPh), 121.8 (C6, OPh),
the H NMR spectra was carried out using the 2D
1
123.9 (C4, OPh), 126.1 (Сp), 128.0 (Сo), 128.5 (Сm),
homonuclear COSY correlation method. The signals of
carbon atoms were assigned basing on the analysis of
the 2D heteronuclear HSQC and HMBC correlation
methods.
2
138.0 d (C1, OPh, JPС = 6.5 Hz), 140.6 d (C2, OPh,
3
3JPС = 3.4 Hz), 141.6 d (Cipso, JPС = 14.0 Hz). 31P
NMR spectrum (CDCl3): δP 56.2 ppm. Found, %: С
72.56; Н 6.73; N 3.76; Р 8.25. С22Н24NO2P. Calculated,
%: С 72.31; Н 6.62; N 3.83; Р 8.48.
ACKNOWLEDGMENTS
O-(2-Aminophenyl) bis(2-phenylethyl)phosphino-
thioate (5b). Yield 225 mg (59%), viscous liquid. Н
This work was supported by the Russian
Foundation for Basic Research (grant no. 18-33-00120
mol_a) using the equipment of the Baikal Analytical
Center for Joint Use of the Siberian Branch of the
Russian Academy of Sciences.
1
NMR spectrum (CDCl3), δ, ppm: 2.36–2.54 m (4Н,
СН2Р), 2.92–3.11 m (4Н, PhСН2), 6.73 d. d (1Н, H5,
OPh, 3J5–4 ≈ 3J5–6 = 7.7 Hz), 6.80 d (1Н, H3, OPh, 3JHH
=
7.7 Hz), 7.01 d. d (1Н, H4, OPh, 3J4–3 ≈ 3J4–5 = 7.7 Hz),
7.18–7.20 m, 7.22–7.26 m and 7.30–7.33 m (11Н,
Ph + H6, OPh). 13C NMR spectrum (CDCl3), δC, ppm:
CONFLICT OF INTERESTS
No conflict of interests was declared by the authors.
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1
29.1 d (PhСН2, JPС = 2.8 Hz), 36.4 d (СН2Р, JPС
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(Сm), 138.7 d (C1, OPh, JPС = 10.1 Hz), 139.2 d (C2,
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