Oxidative cross-coupling of secondary phosphine chalcogenides with amino alcohols and aminophenols: aspects of the reaction chemoselectivity

Article abstract of DOI:10.1039/d1ob00287b

Secondary phosphine chalcogenides react with primary amino alcohols under mild conditions (room temperature, molar ratio of the initial reagents 1?:?1) in a CCl₄/Et₃N oxidizing system to chemoselectively deliver amides of chalcogenop

Full text of DOI:10.1039/d1ob00287b

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Biomolecular Chemistry
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Oxidative cross-coupling of secondary phosphine
chalcogenides with amino alcohols and
aminophenols: aspects of the reaction
chemoselectivity†
Cite this: DOI: 10.1039/d1ob00287b
Kseniya O. Khrapova, Anton A. Telezhkin, Pavel A. Volkov, Lyudmila I. Larina,
Dmitry V. Pavlov, Nina K. Gusarova and Boris A. Trofimov
*
Secondary phosphine chalcogenides react with primary amino alcohols under mild conditions (room
temperature, molar ratio of the initial reagents 1 : 1) in a CCl /Et N oxidizing system to chemoselectively
4
3
Received 16th February 2021,
Accepted 22nd March 2021
deliver amides of chalcogenophosphinic acids with free OH groups. Under similar conditions, mono-
cross-coupling between secondary phosphine chalcogenides and 1,2- or 1,3-aminophenols proceeds
only with the participation of phenolic hydroxyl to give aminophenylchalcogenophosphinic O-esters. The
yields of the synthesized functional amides or esters are 60–85%.
DOI: 10.1039/d1ob00287b
rsc.li/obc
phosphorylation of amines with dialkyl phosphites in the pres-
Introduction
8
ence of bases and CCl
4
. This reaction still draws attention of
9
In organoelement chemistry, the synthesis of fundamentally synthetic chemists as evidenced by numerous publications. In
new molecules and materials, including organophosphorus recent decades, the oxidative cross-coupling of secondary
ones, is becoming increasingly topical. Organophosphorus phosphine chalcogenides with various HN-, HO- and HS-com-
10
compounds bearing P–N or P–O bonds are attracting growing pounds has been successfully implemented and studied. At
1
–6
interest thanks to a wide range of their applications.
Some the same time, the data on the interaction of secondary phos-
of these compounds, namely amides and esters of chalcogen- phine chalcogenides with compounds containing simul-
ophosphinic acids, find application in the directed synthesis taneously different XH groups (where X = N, O, S) are limited
1
of biologically active molecules, such as chemotherapeutic to the publication on the cross-coupling of diphenylphosphine
1
a
1b
11
agents against Chagas disease,
acetylcholinesterase
4
or oxide with 2-aminoethanol or 3-aminopropanol in CCl /
1
c
HIV-1 non-nucleoside reverse transcriptase inhibitors, and CH Cl medium affording chalcogenophosphinic amides. The
anticancer drugs, and as ligands for metal complex cata- reaction occurs in the presence of 30–50% aq. NaOH that is
lysts, intermediates for the design of semiconductor nano- unacceptable for secondary phosphine sulfides and phosphine
materials, fluorescent labels for mercury ion determination,
2
2
1
e
2
3
4
selenides because of their disproportionation under the alka-
line conditions. Besides, we have recently received signal
5
6
12
flame retardants, and agrochemicals.
Traditional methods for the synthesis of chalcogenopho- information on the interaction of available (obtained from red
1
3
sphinic acid derivatives are not environmentally friendly phosphorus and styrene ) bis(2-phenylethyl)phosphine
because of the use of toxic phosphoryl halides sensitive to chalcogenides with 2-aminophenol in the CCl /Et N system
Therefore, the development of a chemoselectively leading to aminophenylchalcogenophosphi-
4
3
2
c,7
moisture and air oxygen.
new general and efficient methodology for the synthesis of nic O-esters.
chalcogenophosphinic acid derivatives, including functional Herein, for the first time we have conducted and studied
1
4
ones, is an urgent challenge. A simple and convenient the reaction of secondary phosphine sulfides and phosphine
approach to the preparation of chalcogenophosphinic acids selenides with amino alcohols in the CCl /Et N system, deter-
4
3
amides and esters is based on the Atherton–Todd reaction, mined its chemoselectivity and synthesized new functional
derivatives of chalcogenophosphinic acids. In addition, to
determine the generality and peculiarities of similar cross-
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian
couplings, we have carried out this reaction involving various
Academy of Sciences, 1 Favorsky St., 664033 Irkutsk, Russian Federation.
secondary phosphine oxides, phosphine sulfides, phosphine
E-mail: boris_trofimov@irioch.irk.ru; Fax: +7 395 241 9346
selenides and 1,2- and 1,3-aminophenols, including functional
†
Electronic supplementary information (ESI) available: Quantum chemical cal-
culations and copies of NMR spectra. See DOI: 10.1039/d1ob00287b
ones.
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Results and discussion
To obtain preliminary data on the possible direction of the
studied cross-coupling, we conducted a competitive reaction
among aliphatic amine, alcohol and secondary phosphine Scheme 2 Formation of chalcogenophosphinic anhydride 7.
chalcogenide. It turned out that stirring a mixture of 1-butyla-
mine, 1-butanol and bis(2-phenylethyl)phosphine sulfide 1a or
bis(2-phenylethyl)phosphine selenide 1b (all three reagents
were taken in an equal molar ratio) at room temperature (5 h, we have shown that a change in the ratio of the initial reagents
CCl /Et
N system) leads to the chemoselective formation of the (secondary phosphine selenide : amino alcohol = 2 : 1, r.t. or
In the example of bis(2-phenylethyl)phosphine selenide 1b
4
3
3
1
corresponding chalcogenophosphinic amides 2a and 2b ( P 50–55 °C) allows carrying out the cross-coupling simul-
NMR data). In this case, 1-butylamine completely wins the taneously on both functional groups of amino alcohol to
competition for phosphine chalcogenide (Scheme 1), the obtain the corresponding N,O-diselenophosphinate 6 in a
3
1
yields of amides 2a and 2b being 82–84%.
28–32% yield ( P NMR data). However, along with N,O-disele-
The oxidative cross-coupling between secondary phosphine nophosphinate 6, selenophosphinic amide 4f (20–39%) was
chalcogenides 1a–c and primary amino alcohols 3a and 3b detected in the reaction mixture (Scheme 3).
also proceeds chemoselectively under mild conditions
20–25 °C, 2–4 h, CCl /Et
N, 1 : 3 molar ratio = 1 : 1) to give tried to transfer this cross-coupling to secondary amino alco-
only chalcogenophosphinic amides 4a–f in up to 84% yield hols. However, the interaction between secondary phosphine
Table 1). Possible chalcogenophosphinic O-esters 5 and the chalcogenides 1a and 1b and 2-(benzylamino)-1-ethanol 8
To expand the substrate scope of the studied reaction, we
(
4
3
(
corresponding N,O-dichalcogenophosphinates
6
are not (50–55 °C, 6–9 h, CCl
4 3
/Et N), instead of the expected chalco-
formed under the reaction conditions.
genophosphinic amides, delivered chalcogenophosphinic
3
1
Hereinafter, the reactions were monitored by P NMR spec- O-esters 9a and 9b. This reaction with phosphine selenide 1b
troscopy until complete disappearance of peaks of the initial proceeded quite efficiently to give ester 9b in 73% yield. In the
secondary phosphine chalcogenides. In almost all cases, by- case of phosphine sulfide 1a, which is less reactive in this
products of these reactions were chalcogenophosphinic anhy- cross-coupling process, the yield of the target ester 9a was
drides 7 (up to 5%) formed from secondary phosphine chalco- 46%; a by-product, bis(2-phenylethyl)thiophosphinic anhy-
1
5
31
genides 1 according to the known data (Scheme 2).
dride 7a, was formed in a comparable amount (≈50%,
P
NMR data) (Scheme 4).
To further define the scope and chemoselectivity of this
protocol, we subjected aromatic compounds to oxidative cross-
coupling with secondary phosphine chalcogenides. To start
Scheme 1 A competitive reaction of 1-butylamine and 1-butanol with
a secondary phosphine chalcogenide.
Table 1 Reaction of secondary phosphine chalcogenides with primary
a
amino alcohols
Scheme 3 Reaction of secondary phosphine chalcogenide 1b with
amino alcohol 3b (1b : 3b molar ratio = 2 : 1).
a
Reagents and conditions: phosphine chalcogenides 1a–c (1.0 mmol),
amino alcohols 3a and 3b (1.0 mmol), Et
0–25 °C.
3
N (1.0 mmol), CCl
4
(3 mL), Scheme 4 Reaction of secondary phosphine chalcogenides with a sec-
2
ondary amino alcohol.
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with, we conducted a competitive reaction between aniline, ganylchalcogenophosphinic acids 12a–k in 60–85% yields
phenol and secondary phosphine chalcogenide 1b (rt, 1 h, (Table 2).
CCl
4
/Et
3
N, molar ratio of the reagents is 1 : 1 : 1).
The high chemoselectivity of this reaction also remained
To our surprise, only phenol reacted with phosphine sele- intact when a two-fold molar excess of secondary phosphine
nide 1b to yield the corresponding selenophosphinic O-ester chalcogenide with respect to aminophenol was used: neither
1
0 (Scheme 5), which was identified in the reaction mixture by products of the oxidative cross-coupling at the amino group
1
13
31
10c
H, C, and P NMR using an authentic sample. Even no nor dicoupling products (N,O-derivatives of chalcogenopho-
traces of amide, the product of the possible reaction of aniline sphinic acid) were detected in the reaction mixture ( P NMR
with selenide 1b, were formed ( P NMR data).
3
1
3
1
data) under similar conditions (20–25 °C, CCl
4 3
/Et N).
Next, we implemented phosphorylation of 3-aminophenol
To confirm the practicability and scalability of the process,
1
1a, 2-amino-5-nitrophenol 11b, and 2-amino-3-pyridinol 11c the gram-scale synthesis of compound 12j was successfully
by secondary phosphine chalcogenides 1a–h in the CCl /Et performed (Scheme 6). Phosphine selenide 1b (3 mmol) and
4
3
N
system. The oxidative cross-coupling of the initial reagents pro- aminophenol 11a (3 mmol) reacted facilely under the above
ceeded under mild conditions (20–25 °C, molar ratio 1 : 11 = conditions without any loss in the efficiency and
1
: 1). The reaction turned out to be strictly chemoselective: chemoselectivity.
1
6
only the OH function of aminophenols underwent phosphoryl-
Apparently, the reaction of secondary phosphine chalco-
ation to furnish the corresponding aminophenyl esters of dior- genides with amino alcohols and aminophenols starts with
deprotonation of secondary phosphine chalcogenide 1 by tri-
ethylamine (Scheme 7). According to the calculations (see also
the ESI, Table S2†), the barrier for this stage is +94–114 kcal
−
1
mol , so this is probably the rate-limiting step. The resulting
P,X-ambident chalcogenophosphinite-anion A participates in
single electron transfer (SET) with a molecule of CCl to give
4
the free radical of secondary phosphine chalcogenide B and
Scheme 5 A competitive reaction of phenol and aniline with a second- the anion radical C. The interaction of species B and C leads
ary phosphine chalcogenide.
to in situ generation of chalcogenophosphoryl chloride D and
CCl carbanion and does not affect the reaction rate, since it
3
−
proceeds in the cell and is energetically favorable in general
Table 2 The scope of the chemoselective phosphorylation of (ΔE −7.6–30.7 kcal mol− , see Fig. 1).
1
a
aminophenols
The trichloromethanide anion is protonated by the triethyl-
ammonium cation to regenerate Et N and form chloroform.
Chalcogenophosphoryl chloride D and chloroform have been
identified in the reaction mixture by H, C, and P NMR
spectroscopy.
3
1
13
31
The reaction between chloride D and primary amino
alcohol 3 in the presence of Et
3
N results in the target amides 4
(
Scheme 8). The chemoselective formation of chalcogenopho-
sphinic amides 4 at an equimolar ratio of the starting reagents
can be explained by a higher N-nucleophilicity of primary
Scheme 6 Gram-scale synthesis of 12j.
a
Reagents and conditions: phosphine chalcogenides 1a–h (1.0 mmol),
aminophenols 11a–c (1.0 mmol), Et
dioxane (1 mL), 20–25 °C.
3 4
N (1.0 mmol), CCl (3 mL), 1,4-
Scheme 7 A plausible reaction mechanism.
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phenylethyl)phosphoroselenoyl]oxy}-2,2,6,6-tetramethyl-
piperidine, thus completely preventing the formation of chlor-
ide D (see also the ESI† for the experiment details).
As observed from Tables 1, 2 and Scheme 4, the reaction
rate considerably depends on the nature of the chalcogen in
secondary phosphine chalcogenides. For secondary phosphine
oxides, in comparison with phosphine sulfides and selenides,
the barrier for the formation of radical B from anion A (ΔE
7–20 kcal mol− ) is smaller and the energetic effect of the for-
1
+
mation of chloride D is greater (Fig. 1).
However, despite the fact that the stage of the formation of
chalcogenophosphoryl chloride is thermodynamically more
favorable for phosphine oxides, analogous phosphine sulfides
and especially phosphine selenides turned out to be more
reactive in the studied process (e.g., compare Table 2, 12b, 12e,
and 12j). Apparently, the rate-determining step of the oxidative
cross-coupling is the stage of nucleophilic substitution of the
halogen atom at the phosphorus atom of the chalcogenopho-
sphoryl group in chloride D (Schemes 8 and 9). Extended cal-
culations for this stage are in progress and will be published
later.
Fig. 1 Energy profiles for the formation of chlorides D.
It is noteworthy that the reactivity order for secondary phos-
phine chalcogenides observed in this work (Table 2, Se > S >
Scheme 8 Formation of chalcogenophosphinic amides 4.
1
6d
O) is inverse to that previously published.
This is probably
due to differences in the nature of the substrates used in both
works.
amino alcohols compared to their O-nucleophilicity (similar to
the competitive reaction of 1-butylamine and 1-butanol with
secondary phosphine chalcogenide, Scheme 1). The observed
lower reactivity of the secondary amino group is apparently
due to the electron-withdrawing effect of the benzyl group and
steric hindrance created by bulky substituents at the nitrogen
atom in secondary amino alcohol 8 that decreases its
N-nucleophilicity.
Substituents at the phosphorus atom also have a significant
1
8
effect on the reaction progress. Bulkier (and less acidic ) bis
2-phenylethyl)phosphine oxide turned out to be less reactive
than diphenylphosphine oxide (compare Table 2, 12a and
2b). The longest reaction time (14 and 16 h) was observed for
phosphine chalcogenides with the bulkiest substituent, PhCH
Me)CH (Table 2, 12g,k), which clearly indicates the impor-
(
1
(
2
tance of steric shielding of the phosphorus atom.
The change in the cross-coupling chemoselectivity upon re-
placement of primary amino alcohols with aminophenols is
Among the studied aminophenols, 2-amino-3-pyridinol 11c
was the most active (Table 2, 12d,i) which is in accordance
with Scheme 9. Since pyridinols seem to be more acidic than
probably due to deprotonation of aminophenols by Et N
3
under the reaction conditions (Scheme 9). The resulting
phenolate anion has a considerably higher nucleophilicity
1
9
the corresponding phenols, they should generate phenolate
anions in a higher concentration.
1
7
than an aromatic amino group that allows directing the
process exclusively to the formation of O-esters 12.
The proposed reaction mechanism including the gene-
ration of the free radical of secondary phosphine chalcogenide
B (Scheme 7) has been confirmed experimentally. So, while
Conclusions
In conclusion, we have developed a convenient protocol for the
directed highly chemoselective synthesis of new prospective
functional derivatives of chalcogenophosphinic acids, amides
with a free hydroxyl function and esters with an amino group,
thus opening a way to their further modification, including
with pharmacophore groups.
stirring bis(2-phenylethyl)phosphine selenide 1b, Et
TEMPO (their molar ratio being 1 : 1 : 1) in CCl4 at r.t.
10 min), TEMPO quantitatively trapped selenophosphoryl rad-
3
N and
(
icals of type B to deliver the corresponding adduct, 1-{[bis(2-
Experimental
General information
All reactions were carried out under an argon atmosphere.
Amino alcohols, aminophenols, 1-butylamine, 1-butanol, and
Scheme 9 Formation of chalcogenophosphinic esters 12.
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diphenylphosphine oxide 1d are commercial reagents NCH
2
CH
2
CH
̲
2
); 1.40–1.47 (m, 2H, NCH
2
CH
̲
2
); 1.95 (br s, 1H,
(Aldrich). Secondary phosphine chalcogenides 1a–c,e–h were NH); 2.22–2.43 (m, 4H, CH P); 2.79–2.86 (m, 2H, CH N);
2 2
1
3
1
prepared from styrene, 4-chlorostyrene, α-methylstyrene and 2.93–3.09 (m, 4H, PhCH
2
); 7.22–7.34 (m, 10H, Ph). C{ H}
): δ 13.7 (Me); 19.8 (NCH CH );
was monitored using P NMR spectra by the disappearance of 29.1 (d, PhC ̲H , J = 2.3 Hz); 33.5 (d, NCH C ̲H , J = 7.7
2 PC 2 2
2
0
elemental phosphorus as previously described. The reaction NMR (100.62 MHz, CDCl
3
2
2 2
C̲H
PC
3
1
2
3
1
2
peaks of the initial secondary phosphine chalcogenides.
Hz); 34.9 (d, CH
The H, C, N, P, and Se NMR spectra were recorded Hz); 126.4 (C ); 128.3 (C
on Bruker DPX 400 and Bruker AV-400 spectrometers (400.13, Hz). N NMR (40.56 MHz, CDCl ): δ −334.7. P NMR
2
P, JPC = 54.7 Hz); 41.8 (d, CH
2
N, JPC = 4.2
1
13
15
31
77
3
p
m
); 128.6 (C ); 140.5 (d, C , JPC = 14.6
o
i
1
5
31
3
1
1
00.62, 40.56, 161.98, and 76.31 MHz, respectively) in CDCl
3
,
3
(161.98 MHz, CDCl ): δ 64.2 (+d-satellites, JPSe = 723.8 Hz).
Se NMR (76.31 MHz, CDCl
7
7
1
DMSO-d , and acetone-d solutions and referenced to HMDS
6
6
3
): δ −316.2 (d, JPSe = 723.8 Hz).
1
13
15
31
77
(
H, C), MeNO2 ( N), H PO ( P), and Me Se ( Se). The IR (neat): νmax = 3061, 3026, 2955, 2929, 2866, 1602, 1494,
3
4
2
1
assignment of signals in H spectra was performed using the 1453, 1399, 1212, 1129, 1087, 1031, 950, 908, 845, 748, 700,
D homonuclear correlation method COSY. The resonance 579, 477 cm− . Anal. calcd for C20
H28NPSe: C 61.22; H 7.19; N
1
2
1
3
signals of C were assigned with the application of 2D hetero- 3.57; P 7.89; Se 20.12. Found: C 61.43; H 7.30; N 3.49; P 7.72;
nuclear correlation methods HSQC and HMBC. The values of δ Se 19.95.
1
5
1
15
N were measured through the 2D H– N HMBC experiment.
Reaction of secondary phosphine chalcogenides 1a–c with
FT-IR spectra were obtained with a Varian 3100 FT-IR spectro- amino alcohols 3a and 3b and 8: general procedure. To a solu-
meter. The C, H, N microanalyses were performed on a Flash tion of secondary phosphine chalcogenides 1a–c (1.0 mmol) in
EA 1112 Series elemental analyzer. The Cl, P, S, and Se con- CCl (3 mL), Et N (101 mg, 1.0 mmol) was added. The mixture
4 3
tents were determined by the combustion method. The opti- was stirred at 20–25 °C for 10 min. Then, amino alcohols 3a or
mized geometries and energies of the reactants were calculated 3b or 8 (1.0 mmol) were added and the reaction mixture was
at the B3LYP/6-311++G(d,p) level of theory using the Gaussian stirred at 20–25 °C for 2–6 h (see also Table 1 and Scheme 4).
2
1
31
0
9 program.
After the completion of the reaction ( P NMR monitoring),
the solvent was removed under reduced pressure. The residue
was purified by column chromatography on SiO , eluent –
2
Typical procedure and analytical data
A competitive reaction of 1-butylamine and 1-butanol with toluene/Et O (10 : 1). The obtained crude product was dried
2
secondary phosphine chalcogenides 1a and 1b: general pro- under vacuum to give amides 4a–f and 9a and 9b.
cedure. To a solution of secondary phosphine chalcogenide 1a
N-(2-Hydroxyethyl)-bis(2-phenylethyl)phosphinothioic amide
1
or 1b (1.0 mmol) in CCl (3 mL), Et N (101 mg, 1.0 mmol) was (4a). Yield: 233 mg (70%); waxy product. H NMR (400.13 MHz,
4
3
added. The mixture was stirred at 20–25 °C for 10 min. Then, a CDCl
solution of 1-butylamine (1.0 mmol) and 1-butanol (1.0 mmol) NH); 2.93–3.06 (m, 6H, PhCH
in CCl (1 mL) was added, and the reaction mixture was stirred = 5.2 Hz); 7.20–7.23 (m, 6H, H ); 7.28–7.32 (m, 4H, H ).
3
): δ 2.17–2.25 (m, 4H, CH
2
P); 2.41, 2.43 (br s, 2H, OH,
3
2
, NCH
2 2
); 3.66 (t, 2H, OCH , JHH
1
3
C
4
o,p
m
3
1
1
2
at 20–25 °C for 5 h. After the completion of the reaction ( P { H} NMR (100.62 MHz, CDCl
3
): δ 28.8 (d, PhC
2
̲H , JPC = 2.9
2
1
2
NMR monitoring), the solvent was removed under reduced Hz); 35.3 (d, CH
pressure. The residue was purified by column chromatography Hz); 63.0 (d, OCH , J = 6.2 Hz); 126.6 (C ); 128.4 (C ); 128.8
2
P, JPC = 63.3 Hz); 43.5 (d, NCH , JPC = 2.4
3
2
PC
p
o
3
15
on SiO
product was dried under vacuum to give amides 2a and 2b.
N-Butyl-bis(2-phenylethyl)phosphinothioic amide
Yield: 283 mg (82%); waxy product. H NMR (400.13 MHz, 1400, 1208, 1109, 1055, 952, 756, 700, 608, 553, 494 cm
2
, eluent – toluene/Et
2
O (10 : 1). The obtained crude (C
m
); 140.8 (d, C
i
,
J
PC = 14.2 Hz). N NMR (40.56 MHz,
3
1
CDCl
3
3
): δ −338.6. P NMR (161.98 MHz, CDCl ): δ 72.0. IR
(2a). (neat): νmax = 3287, 3059, 3026, 2924, 2863, 1603, 1495, 1451,
1
−1
.
3
CDCl
3
): δ 0.95 (t, 3H, Me, JHH = 7.2 Hz); 1.33–1.38 (m, 2H, Anal. calcd for C18
); 1.42–1.47 (m, 2H, NCH CH2); 1.98 (br s, 1H, 9.62. Found: C 64.99; H 7.32; N 4.25; P 9.07; S 9.39.
P); 2.82–2.89 (m, 2H, CH N); N-(3-Hydroxypropyl)-bis(2-phenylethyl)phosphinothioic amide
H24NOPS: C 64.84; H 7.26; N 4.20; P 9.29; S
NCH CH CH
̲
̲
2
2
2
2
NH); 2.16–2.27 (m, 4H, CH
.97–3.07 (m, 4H, PhCH ); 7.24–7.35 (m, 10H, Ph). C{ H} (4b). Yield: 257 mg (74%); waxy product. H NMR (400.13 MHz,
NMR (100.62 MHz, CDCl ): δ 13.7 (Me); 19.8 (NCH CH C
2
2
1
1
3
1
2
2
3
̲
= 5.9 Hz); 2.18–2.31
3
2
2
2
3
2
HH
2
3
2
8.5 (d, PhC
Hz); 34.6 (d, CH
Hz); 126.2 (C ); 128.2 (C ); 128.5 (C ); 140.8 (d, C , J = 14.4 (m, 4H, H ). C{ H} NMR (100.62 MHz, CDCl ): δ 28.7 (d,
̲H
2
, JPC = 2.9 Hz); 33.8 (d, NCH
2
C̲
2
, JPC = 7.3 (m, 6H, CH
2
P, OH, NH); 2.96–3.09 (m, 6H, PhCH
2
2
, NCH ); 3.74
1
2
3
2
P, JPC = 62.9 Hz); 41.0 (d, CH N, JPC = 3.4 (t, 2H, OCH , JHH = 5.7 Hz); 7.24–7.27 (m, 6H, Ho,p); 7.30–7.36
2
2
3
PC
31
13
1
p
m
o
m
3
1
5
2
3
Hz). N NMR (40.56 MHz, CDCl
3
): δ −334.9. P NMR PhC
̲
2
, JPC = 2.8 Hz); 33.8 (d, –CH
JPC = 63.0 Hz); 38.2 (d, NCH , JPC = 2.6 Hz); 59.9
2
2
–, JPC = 6.4 Hz); 35.0 (d,
1
2
(
161.98 MHz, CDCl
3
): δ 70.5. IR (neat): νmax = 3060, 3026, 2953, CH
2
P,
3
2
9
928, 2865, 1602, 1496, 1454, 1400, 1211, 1123, 1089, 1031, (OCH ); 126.5 (C ); 128.4 (C ); 128.7 (C ); 140.8 (d, C , J
=
2
p
o
m
i
PC
−
1
15
31
50, 906, 846, 749, 699, 611, 554, 496 cm . Anal. calcd for 14.4 Hz). N NMR (40.56 MHz, CDCl
3
): δ −335.2. P NMR
C
20
H
28NPS: C 69.53; H 8.17; N 4.05; P 8.97; S 9.28. Found: C (161.98 MHz, CDCl ): δ 71.3. IR (neat): νmax = 3284, 3060, 3027,
3
6
9.71; H 8.25; N 4.12; P 8.73; S 9.07.
2929, 2870, 1602, 1493, 1450, 1402, 1209, 1092, 1072, 1006,
N-Butyl-bis(2-phenylethyl)phosphinoselenoic amide (2b). 950, 859, 752, 700, 608, 554, 496 cm− . Anal. calcd for
1
1
Yield: 329 mg (84%); waxy product. H NMR (400.13 MHz,
CDCl ): δ 0.93 (t, 3H, Me, J
19
C H26NOPS: C 65.68; H 7.54; N 4.03; P 8.91; S 9.23. Found: C
3
= 7.3 Hz); 1.29–1.38 (m, 2H, 65.90; H 7.61; N 4.11; P 8.69; S 9.01.
HH
3
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N-(2-Hydroxyethyl)-bis[2-(4-chlorophenyl)ethyl]phosphinothioic (40.56 MHz, CDCl
Organic & Biomolecular Chemistry
3
1
3
): δ −337.1. P NMR (161.98 MHz, CDCl
3
):
1
1
77
amide (4c). Yield: 326 mg (81%); waxy product. H NMR δ 65.2 (+d-satellites, J
= 719.0 Hz). Se NMR (76.31 MHz,
PSe
1
(
400.13 MHz, CDCl
3
): δ 2.13–2.23 (m, 4H, CH
2
P); 2.88–3.00 (m, CDCl
3
): δ −315.0 (d, JPSe = 719.0 Hz). IR (neat): νmax = 3261,
6
H, PhCH , OH, NH); 3.06–3.11 (m, 2H, NCH
̲
2
2
); 3.69 (t, 2H, 3062, 3027, 2927, 2864, 1602, 1494, 1452, 1400, 1207, 1074,
3
−1
OCH , J = 4.9 Hz); 7.13–7.15 (m, 4H, H ); 7.26–7.28 (m, 4H, 1005, 911, 866, 738, 650, 577, 475 cm . Anal. calcd for
H
=
2
1
2
HH
o
13
1
2
m
). C{ H} NMR (100.62 MHz, CDCl
2.6 Hz); 34.8 (d, CH
.9 Hz); 62.7 (d, OCH , J = 6.3 Hz); 128.8 (C ); 129.3 (C );
32.2 (C
3
): δ 28.0 (d, PhC
P, JPC = 63.0 Hz); 43.4 (d, NCH
̲
2
, JPC
19
C H26NOPSe: C 57.87; H 6.65; N 3.55; P 7.85; Se 20.02. Found:
C 58.04; H 6.72; N 3.62; P 7.66; Se 19.87.
1
2
2
2
, JPC
=
3
O-[2-(Benzylamino)ethyl]-bis(2-phenylethyl)phosphinothioate
2
PC
o
m
3
15
1
p
); 139.0 (d, C
i
, JPC = 14.9 Hz). N NMR (40.56 MHz, (9a). Yield: 195 mg (46%); waxy product.
H
NMR
3
1
CDCl
3
): δ −340.1. P NMR (161.98 MHz, CDCl
3
): δ 71.5. IR (400.13 MHz, CDCl
3
): δ 2.17–2.31 (m, 4H, CH
2
P); 2.86 (t, 2H,
2CH2,
, JHH = 5.2 Hz,
3
(neat): νmax = 3299, 3097, 3035, 2928, 2869, 1648, 1491, 1445, NCH
2̲ CH2, JHH = 5.2 Hz); 2.93–3.02 (m, 5H, PhCH
̲
3
1
5
1
404, 1210, 1097, 1057, 1015, 953, 811, 772, 732, 655, 593, NH); 3.84 (s, 2H, NCH
2
Ph); 4.11 (dt, 2H, OCH
2
12 cm− . Anal. calcd for C18
1
H
22Cl
NOPS: C 53.74; H 5.51; Cl
2
JPH = 9.3 Hz); 7.18–7.34 (m, 15H, Ph).
13
C{ H} NMR
1
2
2
7.62; N 3.48; P 7.70; S 7.97. Found: C 53.91; H 5.60; Cl 17.47; (100.62 MHz, CDCl ): δ 28.8 (d, PhC
̲
3
2
2
PC
1
3
N 3.57; P 7.48; S 7.73.
(d, CH
2
P, JPC = 67.5 Hz); 48.9 (d, NC
̲
2
CH
2
, JPC = 7.1 Hz);
2
N-(3-Hydroxypropyl)-bis[2-(4-chlorophenyl)ethyl]phosphinothioic 53.4 (NC
̲
2
Ph); 64.0 (d, OCH
2
,
J
PC = 6.5 Hz); 126.5 (C ,
p
1
amide (4d). Yield: 341 mg (82%); waxy product. H NMR
P
̲
̲
̲
̲
̲
h
̲
); 128.34
2
p
2
o
2
3
(
400.13 MHz, CDCl
Hz); 2.18–2.33 (m, 4H, CH
.97–3.19 (m, 6H, PhCH , NCH ); 3.85 (t, 2H, OCH , J = 5.3
3
): δ 1.81 (quintet, 2H, –CH
2
–, JHH = 5.4 (C
, P
̲
̲
CH
2
); 128.6 (C
m
m
3
, P
̲
̲C H CH );
2
2
2
P); 2.50, 2.60 (br s, 2H, NH, OH); 139.4 (C
i
2
P
̲
̲
3
15
31
2
̲
P
NMR
2
2
2
HH
1
3
1
Hz); 7.24–7.26 (m, 4H, H
NMR (100.62 MHz, CDCl
o
); 7.37–7.39 (m, 4H, H
m
3
H30NOPS:
2
3
): δ 28.1 (d, PhC
̲H
2
3
1
3
3
3.8 (d, –CH –, J = 6.5 Hz); 34.8 (d, CH P, J = 63.0 Hz); 7.06; N 3.16; P 7.12; S 7.33.
2
PC
2
PC
2
8.4 (d, NCH
); 132.3 (C
40.56 MHz, CDCl ): δ −335.6. P NMR (161.98 MHz, CDCl3): (400.13 MHz, CDCl ): δ 2.36–2.46 (m, 4H, CH P); 2.88 (t, 2H,
2
, JPC = 2.8 Hz); 59.9 (OCH
2
); 128.8 (C
o
15
); 129.7
O-[2-(Benzylamino)ethyl]-bis(2-phenylethyl)phosphinoseleno-
3
1
(C
m
p
); 139.2 (d, C
i
3
,
JPC = 14.8 Hz). N NMR ate (9b). Yield: 343 mg (73%); waxy product. H NMR
1
(
3
3
2
3
δ 70.7. IR (neat): νmax = 3278, 3092, 3032, 2928, 2871, 1644, NCH
̲
2
CH
2 2 2
, JHH = 5.0 Hz); 2.93–3.03 (m, 5H, PhCH̲ CH , NH);
3
2
1
6
5
490, 1443, 1405, 1210, 1092, 1011, 950, 914, 811, 773, 732, 3.86 (s, 2H, NCH̲ Ph); 4.13 (dt, 2H, OCH , JHH = 5.0 Hz, JPH =
2
2
55, 593, 513 cm− . Anal. calcd for C H Cl NOPS: C 54.81; H 9.8 Hz); 7.20–7.38 (m, 15H, Ph). C{ H} NMR (100.62 MHz,
1
13
1
1
9
22
2
2
1
.81; Cl 17.03; N 3.36; P 7.44; S 7.70. Found: C 55.01; H 5.89; CDCl
3
): δ 29.3 (d, PhC
̲
2
CH
2
, JPC = 2.6 Hz); 37.4 (d, CH
2
P, JPC
Ph);
3
Cl 16.90; N 3.43; P 7.28; S 7.49.
= 57.7 Hz); 48.7 (d, NC
2
CH
2
, JPC = 7.2 Hz); 53.4 (NC
̲H
2
2
N-(2-Hydroxyethyl)-bis(2-phenylethyl)phosphinoselenoic amide 65.4 (d, OCH , J = 6.7 Hz); 126.6 (C , P
̲
̲
2
PC
p
2
2
p
1
(
4e). Yield: 308 mg (81%); waxy product. H NMR (400.13 MHz, NCH
CDCl ): δ 2.26–2.36 (m, 4H, CH P); 2.68 (br s, 1H, OH); (C , NCH
.88–3.03 (m, 7H, PhCH 140.4 (d, C , P
2
P
̲
̲
o
, NCH
2
P
̲
̲
, P
̲
̲
CH
2
3
2
m
2
P
̲
̲
m
3
, P
̲
̲
2
3
15
2
=
{
̲
, NCH , NH); 3.63 (t, 2H, OCH , J
4.9 Hz); 7.19–7.21 (m, 6H, Ho,p); 7.26–7.30 (m, 4H, H
̲
̲
2
2
2
HH
i
2
PC
1
3
31
m
).
C
CDCl
3
): δ −343.3. P NMR (161.98 MHz, CDCl
3
): δ 104.5 (+d-
): δ
1
2
1
77
H} NMR (100.62 MHz, CDCl
3
): δ 29.2 (d, PhC
̲
2
, JPC = 2.3 satellites, JPSe = 776.2 Hz). Se NMR (76.31 MHz, CDCl
3
1
2
1
Hz); 35.5 (d, CH P, J = 54.4 Hz); 44.1 (d, NCH , J = 3.1 −300.6 (d, J = 776.2 Hz). IR (neat): νmax = 3155, 3064, 3029,
Hz); 62.4 (d, OCH
2
PC
2
PC
PSe
3
2
, JPC = 6.7 Hz); 126.4 (C
p
o
); 128.3 (C ); 128.6 2924, 2854, 2251, 2221, 1636, 1604, 1495, 1455, 1213, 1134,
3
15
−1
(C
m
); 140.4 (d, C
i
3
,
JPC = 14.8 Hz). N NMR (40.56 MHz, 1031, 910, 735, 650, 581, 465 cm
.
Anal. calcd for
1
CDCl ): δ −340.4. P NMR (161.98 MHz, CDCl ): δ 66.5 (+d-sat- C H NOPSe: C 63.83; H 6.43; N 2.98; P 6.58; Se 16.78. Found:
ellites,
−
3
3
25 30
1
77
J
PSe = 718.9 Hz). Se NMR (76.31 MHz, CDCl
302.9 (d, JPSe = 718.9 Hz). IR (neat): νmax = 3273, 3060, 3026,
3
): δ C 63.99; H 6.50; N 3.05; P 6.42; Se 16.63.
1
Reaction of secondary phosphine chalcogenides 1a–h with
2
8
5
925, 2862, 1602, 1495, 1450, 1398, 1208, 1107, 1054, 952, 913, aminophenols 11a–c: general procedure. To a solution of sec-
−
1
75, 750, 701, 577, 471 cm . Anal. calcd for C18
6.84; H 6.36; N 3.68; P 8.14; Se 20.76. Found: C 57.02; H 6.44; of CCl
1.0 mmol) was added. The mixture was stirred at 20–25 °C for
N-(3-Hydroxypropyl)-bis(2-phenylethyl)phosphinoselenoic amide 10 min. Then, aminophenols 11a–c (1.0 mmol) were added,
H
24NOPSe: C ondary phosphine chalcogenides 1a–h (1.0 mmol) in a mixture
4
(3 mL) and 1,4-dioxane (1 mL), Et N (101 mg,
3
N 3.75; P 7.92; Se 20.61.
1
(4f). Yield: 331 mg (84%); waxy product. H NMR (400.13 MHz, and the reaction mixture was stirred at 20–25 °C for 2–4 h (see
3
31
CDCl ): δ 1.68 (quintet, 2H, –CH –, J
= 5.9 Hz); 2.24–2.42 also Table 2). After the completion of the reaction ( P NMR
3
2
HH
(
(
2 2 2
m, 6H, CH P, OH, NH); 2.96–3.07 (m, 6H, PhCH̲ , NCH ); 3.73 monitoring), the solvent was removed under reduced pressure,
3
13
1
2
t, 2H, OCH , JHH = 5.7 Hz); 7.24–7.35 (m, 10H, Ph). C{ H} and 1,4-dioxane (3 mL) was added to the residue. The precipi-
2
NMR (100.62 MHz, CDCl ): δ 29.3 (d, PhC ̲H , J = 2.3 Hz); tated white solid (triethylammonium chloride) was filtered,
2 PC
3
3
3
3
1
3.6 (d, –CH
9.2 (d, NCH
2
–, JPC = 6.9 Hz); 35.5 (d, CH
, JPC = 3.2 Hz); 59.9 (OCH
2
P, JPC = 54.6 Hz); and the solvent was removed from the filtrate under reduced
); 126.6 (C ); 128.4 pressure. The residue obtained was reprecipitated from CHCl
2
2
2
p
15
3
3
(C ); 128.8 (C ); 140.5 (d, C , JPC = 14.5 Hz). N NMR to hexane (for compounds 12b,e,g,h,j,k) or washed with Et O
o
m
i
2
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2 mL × 7) (for 12a,c,d,f,i), and then dried under vacuum to
Paper
(
d
6
): δ 2.24–2.32 (m, 4H, CH ); 6.73
(br s, 2H, NH ); 6.79 (d, 1H, H , OPh, J = 9.1 Hz); 7.26 (d,
HH
2
P); 2.76–2.89 (m, 4H, PhCH
2
3
give esters 12a–k.
2
3
3
3
Gram-scale synthesis of compound 12j. To a solution of sec- 4H, H
ondary phosphine selenide 1b (964 mg, 3.0 mmol) in a 8.1 Hz); 7.87 (d, 1H, H
o
, P
̲
̲
, JHH = 8.1 Hz); 7.33 (d, 4H, H
m
, P
2
̲h ̲C H , JHH =
3
4
, OPh, JHH = 9.1 Hz); 8.08 (s, 1H, H ,
6
1
3
mixture of CCl (9 mL) and 1,4-dioxane (3 mL), Et N (304 mg, OPh). C{ H} NMR (100.62 MHz, DMSO-d ): δ 26.3 (d, PhC
̲
H ,
4
3
6
2
2
1
3
1
.0 mmol) was added. The mixture was stirred at 20–25 °C for
0 min. Then, aminophenol 11a (462 mg, 3.0 mmol) was 116.7 (C
CH ); 130.8 (C , P ̲h ̲
J
PC = 3.2 Hz); 29.0 (d, CH
, OPh); 123.5 (C , OPh); 128.3 (C
CH ); 135.1 (C , OPh); 135.3 (d, C , OPh,
2
P, JPC = 85.1 Hz); 113.2 (C
4
, OPh);
6
3
o
, P CH
̲
̲
2 m
); 130.0 (C ,
added, and the reaction mixture was stirred at 20–25 °C for 4 h
P
̲
̲
2
p
2
5
2
3
1
3
3
(
see also Scheme 6). After the completion of the reaction ( P
J
i
, P
̲
̲
2
, JPC = 15.6 Hz); 147.6 (C
): δ −306.1 (NH ); −9.6
pressure, and 1,4-dioxane (9 mL) was added to the residue. (NO2). P NMR (161.98 MHz, DMSO-d ): δ 60.1. IR (KBr): ν
1
,
1
5
NMR monitoring), the solvent was removed under reduced OPh). N NMR (40.56 MHz, DMSO-d
6
2
3
1
6
max
The precipitated white solid (triethylammonium chloride) was = 3181, 3060, 1633, 1593, 1511, 1403, 1315, 1220, 1193, 1047,
−
1
filtered, and the solvent was removed from the filtrate under 1087, 1012, 964, 902, 851, 806, 742, 685, 655, 514 cm . Anal.
reduced pressure. The residue obtained was reprecipitated calcd for C H Cl N O P: C 55.13; H 4.42; Cl 14.79; N 5.84; P
2
2
21
2 2 4
from CHCl
3
to hexane, and then dried under vacuum to give 6.46. Found: C 55.30; H 4.47; Cl 14.63; N 5.90; P 6.29.
O-(2-Aminopyridin-3-yl) bis(2-phenylethyl)phosphinothioate
-Amino-5-nitrophenyl diphenylphosphinate (12a). Yield: (12d). Yield: 314 mg (82%); white powder, mp 139–142 °C
ester 12j (yield: 1.19 g, 84%).
2
2
1
66 mg (75%); yellow powder, mp 205–206 °C (washed with (washed with Et
2
O). H NMR (400.13 MHz, acetone-d
6
+
1
Et
2
O). H NMR (400.13 MHz, DMSO-d
6
): δ 6.68 (br s, 2H, NH
= 8.9 Hz); 7.56–7.64 (m, 6H, Hm,p, PhCH̲ ); 5.69 (br s, 2H, NH ); 6.57 (dd, 1H, H , OPh, J = 7.8
2 2 5 HH
3
2 6 2
); DMSO-d ): δ 2.53–2.63 (m, 4H, CH P); 2.93–3.05 (m, 4H,
3
3
6
.78 (d, 1H, H , OPh, J
3
HH
3
PhP); 7.79 (d, 1H, H
4
, OPh, JHH = 8.9 Hz); 7.96–8.00 (m, 4H, Hz, JHH = 4.8 Hz); 7.18–7.31 (m, 10H, Ho,m,p, P
̲
̲
2
); 7.63 (d,
3
1
3
1
3
H
o
, PhP); 8.22 (s, 1H, H
6
, OPh). C{ H} NMR (100.62 MHz, 1H, H
6
13
, OPh, JHH = 7.8 Hz); 7.80 (d, 1H, H
4
3
1
DMSO-d ): δ 113.7 (C , OPh); 116.5 (d, C , OPh, J = 3.8 Hz); Hz). C{ H} NMR (100.62 MHz, acetone-d + DMSO-d ): δ 29.3
6
4
6
PC
6
6
3
2
1
1
22.5 (C
3
, OPh); 128.9 (d, C
PhP, JPC = 136.2 Hz); 131.5 (d, C
m
, PhP, JPC = 13.3 Hz); 130.0 (d, C
i
,
(d, PhC
, PhP, JPC = 10.7 Hz); 133.0 (C , OPh); 127.0 (C
d, C , PhP, J = 2.9 Hz); 134.9 (C , OPh); 135.4 (d, C , OPh, 129.0 (C , P CH ); 129.3 (C , P
̲
2
, JPC = 2.2 Hz); 36.7 (d, CH
, P CH ); 128.7 (d, C
CH ); 134.3 (d, C , OPh, J
2
P, JPC = 65.6 Hz); 112.9
1
2
3
o
5
p
̲
̲
2
6
, OPh, JPC = 4.0 Hz);
4
3
(
̲
̲
̲
̲
=
PC
p
PC
5
2
m
2
o
2
2
3
2
15
3
J
PC = 7.8 Hz); 147.1 (d, C
1
, OPh,
J
PC = 4.7 Hz). N NMR 10.0 Hz); 141.7 (d, C
i
, P
̲
3
1
2
15
(
(
40.56 MHz, DMSO-d ): δ −307.6 (NH
6
2
2 1
); −11.4 (NO ). P NMR 153.8 (d, C , OPh, J
3
1
161.98 MHz, DMSO-d ): δ 34.0. IR (KBr): ν
= 3189, 3058, acetone-d + DMSO-d ): δ −312.9 (NH ); −104.8 (N). P NMR
6
max
6
6
2
2
1
734, 1637, 1593, 1519, 1481, 1439, 1306, 1219, 1193, 1133, (161.98 MHz, acetone-d
088, 963, 900, 860, 821, 736, 694, 569, 528 cm . Anal. calcd 3136, 3063, 3029, 2960, 2930, 2864, 1630, 1601, 1561, 1482,
6
+ DMSO-d
6
): δ 109.4. IR (KBr): νmax =
−
1
for C H N O P: C 61.02; H 4.27; N 7.91; P 8.74. Found: C 1449, 1395, 1273, 1182, 1129, 1072, 1028, 925, 843, 783, 757,
1
8
15 2 4
696, 613, 500, 425 cm− . Anal. calcd for C21
1
H N OPS: C 65.95;
6
1.21; H 4.35; N 7.98; P 8.58.
-Amino-5-nitrophenyl bis(2-phenylethyl)phosphinate (12b). H 6.06; N 7.32; P 8.10; S 8.38. Found: C 66.11; H 6.13; N 7.38; P
Yield: 246 mg (60%); yellow powder, mp 139–141 °C (reprecipi- 7.94; S 8.11.
23 2
2
1
tated from CHCl
3
to hexane). H NMR (400.13 MHz, CDCl
3
): δ
O-(2-Amino-5-nitrophenyl) bis(2-phenylethyl)phosphinothio-
2
2
P
.14–2.23 (m, 4H, CH P); 2.90–2.99 (m, 4H, PhCH ); 3.10 (br s, ate (12e). Yield: 328 mg (77%); yellow powder, mp 127–129 °C
2
2
3
1
H, NH ); 6.74 (d, 1H, H , OPh, J = 8.8 Hz); 7.16 (d, 4H, Ho, (reprecipitated from CHCl to hexane). H NMR (400.13 MHz,
2
3
HH
3
3
̲
h
̲
CH
2
,
J
HH = 8.2 Hz); 7.21–7.25 (m, 4H, H
, P CH ); 7.93 (dd, 1H, H , OPh, JHH
= 2.6 Hz); 7.97 (dd, 1H, H , OPh, J
m
, P
̲
̲
2
); CDCl
3
): δ 2.38–2.46 (m, 4H, CH
2
P); 2.94–3.04 (m, 4H, PhCH
̲
2
);
3
3
7
.28–7.33 (m, 2H, H
p
̲
̲
2
4
=
4.57 (br s, 2H, NH
2
); 6.70 (d, 1H, H
CH ); 7.90 (dd, 1H, H , OPh, J
HH
3
, OPh, JHH = 8.8 Hz);
4
4
3
8
J
.8 Hz, J
= 2.6 Hz, 7.15–7.30 (m, 10H, Ho,m,p, P ̲h ̲
HH
6
HH
2
4
4
13
1
4
4
HH = 1.4 Hz). C{ H} NMR (100.62 MHz, CDCl
3
): δ 28.0 (d, = 8.8 Hz, JHH = 2.3 Hz); 8.02 (dd, 1H, H
6
, OPh, JHH = 2.3 Hz,
HH = 1.6 Hz). C{ H} NMR (100.62 MHz, CDCl ): δ 29.1 (d,
H , J = 2.6 Hz); 36.5 (d, CH P, J = 63.3 Hz); 114.8 (C3,
2
1
4
13
1
PhC
̲H
2
, JPC = 3.0 Hz); 29.9 (d, CH
2
P, JPC = 85.5 Hz); 115.1 (C
4
,
J
3
3
2
1
OPh); 118.0 (d, C , OPh, J = 4.0 Hz); 122.9 (C , OPh); 126.9 PhC
̲
6
PC
3
2
PC
2
PC
3
(C
p
, P
̲
h
̲
CH
2
); 128.2 (C
o
, P
̲
̲
2
); 128.9 (C
m
, P
̲
̲
2
); 136.4 (d, OPh); 118.2 (d, C
6
, OPh, JPC = 3.9 Hz); 122.8 (C
4
, OPh); 126.9
); 136.5 (d,
CH ,
3
C
2
, OPh, JPC = 9.7 Hz); 138.3 (C
5
, OPh); 140.0 (d, C
i
15
, P CH (C , P CH ); 128.4 (C
2
,
p
̲
̲
2
o
, P CH ); 129.0 (C , P CH
̲
̲
2
m
̲
̲
2
3
2
3
JPC = 13.7 Hz); 146.0 (d, C , OPh, JPC = 2.8 Hz). N NMR C , OPh, J = 10.1 Hz); 138.4 (C , OPh); 139.8 (d, C , P
̲h
̲
1
2
PC
5
i
15
2
31
3
2
(
(
40.56 MHz, CDCl
161.98 MHz, CDCl
3
): δ −316.6 (NH
): δ 60.7. IR (neat): νmax = 3202, 3065, 3027, (40.56 MHz, CDCl
2
); −10.8 (NO
2
). P NMR
J
PC = 14.7 Hz); 146.2 (d, C
1
, OPh, JPC = 3.3 Hz). N NMR
3
1
3
3
): δ −316.3 (NH
2
); −11.4 (NO
2
). P NMR
2
1
923, 1629, 1595, 1512, 1495, 1452, 1401, 1312, 1199, 1082, (161.98 MHz, CDCl ): δ 108.2. IR (neat): ν
= 3202, 3064,
3
max
028, 965, 907, 858, 786, 740, 703, 641, 495, 451 cm− . Anal. 3027, 2923, 2857, 1620, 1588, 1513, 1455, 1397, 1309, 1199,
1
−1
calcd for C22
C 64.56; H 5.72; N 6.89; P 7.37.
H
23
N
2
O
4
P: C 64.38; H 5.65; N 6.83; P 7.55. Found: 1150, 1083, 1030, 960, 899, 843, 752, 700, 620 cm . Anal.
calcd for C H N O PS: C 61.96; H 5.44; N 6.57; P 7.26; S 7.52.
2
2
23 2 3
2
-Amino-5-nitrophenyl bis[2-(4-chlorophenyl)ethyl]phosphi- Found: C 62.15; H 5.51; N 6.64; P 7.08; S 7.35.
nate (12c). Yield: 398 mg (83%); brown powder, mp
O-(2-Amino-5-nitrophenyl) bis[2-(4-chlorophenyl)ethyl]phos-
1
1
31–133 °C (washed with Et O). H NMR (400.13 MHz, DMSO- phinothioate (12f). Yield: 366 mg (74%); yellow powder, mp
2
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Paper
96–198 °C (washed with Et
Organic & Biomolecular Chemistry
1
1
3
1
2
O). H NMR (400.13 MHz, DMSO- Hz); 37.6 (d, CH
2
P, JPC = 56.3 Hz); 108.6 (d, C
3
, OPh, JPC = 4.5
3
d ): δ 2.53–2.67 (m, 4H, CH P); 2.79–2.98 (m, 4H, PhCH
̲
); 6.67 Hz); 111.5 (d, C , OPh, J = 4.4 Hz); 112.2 (C , OPh); 126.7
6
2
2
6
PC
4
3
(
br s, 2H, NH
2
); 6.80 (d, 1H, H
3
, OPh, JHH = 9.0 Hz); 7.28 (d, (C
p
, P
̲
̲
2
); 128.4 (C
o
, P
̲
̲
2
); 128.8 (C
m
, P
̲
̲
2
); 130.2 (C
5
,
3
3
3
4
8
8
H, H
o
, P
̲h
̲C H
2
, JHH = 8.2 Hz); 7.35 (d, 4H, H
m
, P
̲
̲
2
, JHH
=
OPh); 140.3 (d, C
i
2
, P
̲
̲
PC = 15.8 Hz); 147.8 (C
2
, OPh);
3
4
15
.2 Hz); 7.87 (dd, 1H, H , OPh, J
= 9.0 Hz, J
= 2.6 Hz); 151.8 (d, C , OPh, J = 9.9 Hz). N NMR (40.56 MHz, CDCl3):
HH 1 PC
4
HH
4
4
13
1
31
.16 (dd, 1H, H
6
, OPh, JHH = 2.6 Hz, JHH = 1.5 Hz). C{ H} δ −322.0 (NH
2
). P NMR (161.98 MHz, CDCl
PSe = 798.0 Hz). Se NMR (76.31 MHz, CDCl ): δ
3
): δ 103.8 (+d-sat-
77
NMR (100.62 MHz, acetone-d
6
1
+ DMSO-d
6
): δ 28.4 (d, PhC
̲
2
,
ellites,
3
2
1
JPC = 2.6 Hz); 36.0 (d, CH P, J = 65.4 Hz); 114.3 (C , OPh); −243.4 (d, J = 798.0 Hz). IR (neat): νmax = 3216, 3059, 3027,
2
PC
3
PSe
3
1
18.6 (d, C
6
, OPh, JPC = 4.3 Hz); 123.0 (C
4
, OPh); 129.1 (C
o
,
2923, 2855, 1611, 1491, 1458, 1398, 1316, 1280, 1210, 1146,
1072, 970, 909, 849, 742, 695, 580, 466 cm− . Anal. calcd for
1
P
̲
h
̲
CH ); 130.8 (C
2
m
, P CH ); 132.0 (C , P
̲
̲
2
p
̲
̲
2
); 136.1 (d, C
2
,
=
3
3
OPh, J = 9.7 Hz); 136.3 (C , OPh); 140.5 (d, C , P
̲
̲
C22H24NOPSe: C 61.68; H 5.68; N 3.27; P 7.23; Se 18.43. Found:
PC
5
i
2
PC
2
15
1
6.7 Hz); 148.7 (d, C
1
, OPh,
J
PC = 3.5 Hz).
); −9.9 (NO
161.98 MHz, DMSO-d ): δ 108.6. IR (KBr): ν = 3200, 3033, ate (12i). Yield: 365 mg (85%); purple powder, mp 150–152 °C
N NMR C 61.90; H 5.75; N 3.35; P 7.09; Se 18.29.
3
1
(40.56 MHz, DMSO-d
6
): δ −310.1 (NH
2
2
). P NMR
O-(2-Aminopyridin-3-yl) bis(2-phenylethyl)phosphinoseleno-
(
6
max
1
2
1
933, 2858, 1619, 1589, 1505, 1491, 1442, 1408, 1306, 1192, (washed with Et
2
O). H NMR (400.13 MHz, DMSO-d
6
): δ
147, 1087, 1016, 955, 839, 809, 745, 655, 514 cm− . Anal. 2.64–2.79 (m, 4H, CH
1
P); 2.83–3.00 (m, 4H, PhCH ); 6.05 (br s,
2
2
3
calcd for C H Cl N O PS: C 53.34; H 4.27; Cl 14.31; N 5.66; P 2H, NH ); 6.53 (dd, 1H, H , OPh, J = 7.6 Hz, J = 4.9 Hz);
2
2
21
2
2
3
2
5
HH
HH
3
6
6
.25; S 6.47. Found: C 53.54; H 4.33; Cl 14.17; N 5.73; P 6.08; S 7.19–7.32 (m, 10H, Ho,m,p, P
.28. 7.6 Hz); 7.77 (d, 1H, H
O-(2-Amino-5-nitrophenyl) bis(2-phenylpropyl)phosphi- (100.62 MHz, DMSO-d ): δ 28.7 (d, PhC
nothioate (12g). Yield: 295 mg (65%); waxy product. The (d, CH
product is a mixture of three stereoisomers in a ratio of 127.9 (d, C
̲
̲
2
3
6
); 7.57 (d, 1H, H , OPh, JHH =
13
1
4
, OPh, JHH = 4.9 Hz). C{ H} NMR
2
̲H , J = 2.2 Hz); 36.2
2 PC
6
1
2
P, JPC = 54.8 Hz); 111.6 (C
5
, OPh); 126.3 (C
, OPh, JPC = 4.3 Hz); 128.3 (C , P CH ); 128.5 (C
P ̲h ̲C H ); 132.9 (d, C , OPh, J = 10.3 Hz); 140.4 (d, C , P ̲h ̲C H ,
2 2 PC i
3 15
p 2
, P ̲h ̲C H );
3
6
m
̲
̲
2
o
,
1
31
1
3
9
.3 : 8.9 : 1 ( H and P NMR data). H NMR (400.13 MHz,
2
3
3
CDCl
3
): δ 1.15, 1.24, 1.32, 1.42 (4 d, Me, JHH = 6.9 Hz, JHH
=
J
PC = 17.1 Hz); 143.6 (C
HH = 6.9 Hz); 1.44–1.50, 1.98–2.06, (40.56 MHz, DMSO-d
.18–2.44 (3 m, 4H, CH P); 3.14–3.22, 3.29–3.42 (2 m, 2H, (161.98 MHz, DMSO-d ): δ 111.2 (+d-satellites, JPSe = 805.2
4
1
, OPh); 152.9 (C , OPh). N NMR
3
3
31
6
.8 Hz,
JHH = 6.8 Hz,
J
6
): δ −312.7 (NH ); −104.7 (N). P NMR
2
1
2
2
6
3
77
1
PhCH
̲
); 4.03 (br s, 2H, NH
2
); 6.55, 6.61 (2 d, 1H, H
3
, OPh, JHH Hz). Se NMR (76.31 MHz, DMSO-d
6
): δ −249.0 (d,
J
PSe
=
=
8.7 Hz); 7.13–7.35 (m, 10H, Ho,m,p, P
̲
̲
3
4
dd, 1H, H , OPh, J
= 8.7 Hz, J
= 2.0 Hz); 7.98–8.01 (m, 1555, 1481, 1452, 1393, 1337, 1271, 1178, 1128, 1072, 1026,
4
HH
HH
1
3
1
−1
1
H, H
6 3
, OPh). C{ H} NMR (100.62 MHz, CDCl ): δ 24.5, 24.6, 926, 842, 754, 725, 703, 670, 575, 470 cm . Anal. calcd for
3
3
3
2
5.0, 25.2 (4 d, Me, JPC = 13.6 Hz, JPC = 15.3 Hz, JPC = 14.5
21 23 2
C H N OPSe: C 58.75; H 5.40; N 6.52; P 7.21; Se 18.39.
Found: C 58.96; H 6.47; N 6.58; P 7.03; Se 18.25.
O-(2-Amino-5-nitrophenyl) bis(2-phenylethyl)phosphinose-
3
2
Hz, J = 13.5 Hz); 34.8, 35.4, 35.6, 35.9 (3 d, s, PhC
̲
=
PC
PC
2
2
4
.2 Hz, JPC = 3.5 Hz, JPC = 2.2 Hz); 42.3, 43.0, 43.8, 44.0 (4 d,
1
1
1
1
2
CH P, JPC = 66.6 Hz, JPC = 63.4 Hz, JPC = 62.6 Hz, JPC = 64.6 lenoate (12j). Yield: 374 mg (79%); yellow powder, mp
1
Hz); 114.0, 114.2, 114.4 (C , OPh); 117.9, 118.2 (3 d, C , OPh, 136–138 °C (reprecipitated from CHCl3 to hexane). H NMR
4
6
3
3
J
PC = 3.9 Hz,
27.0 (C , P
29.0 (C , P
J
PC = 4.0 Hz); 122.3, 122.4 (C
̲h ̲C H); 127.2, 127.3, 127.5 (C , P ̲h ̲C H); 128.8, 128.9, 4H, PhCH̲ ); NH was not detected due to broadening; 6.74 (d,
CH); 136.2, 136.4 (2 d, C , OPh, J = 10.3 Hz); 1H, H , OPh, JHH = 8.9 Hz); 7.20–7.34 (m, 10H, Ho,m,p,
3
, OPh); 126.8, (400.13 MHz, CDCl
3
): δ 2.55–2.63 (m, 4H, CH
2
P); 2.99–3.09 (m,
1
1
1
p
o
2
2
3
3
̲
h
̲
m
2
PC
3
3
4
38.1, 138.3 (C
5
, OPh); 145.1, 145.2, 145.9, 146.0 (4 d, C
P ̲h ̲C H, JPC = 14.1 Hz, JPC = 15.5 Hz, JPC = 12.9 Hz, JPC = 15.3 8.05 (dd, 1H, H , OPh, JHH = 2.4 Hz, JHH = 1.7 Hz). C{ H}
6
Hz); 145.9, 146.0 (2 d, C , OPh, J = 3.8 Hz, J = 4.8 Hz). NMR (100.62 MHz, CDCl ): δ 29.7 (d, PhC
i
,
P
̲
̲
2
4
); 7.95 (dd, 1H, H , OPh, JHH = 8.9 Hz, JHH = 2.4 Hz);
3
3
3
3
4
4
13
1
2
2
2
̲
1
PC
PC
3
2
PC
1
5
31
1
N NMR (40.56 MHz, CDCl
3
): δ −318.9 (NH
2
); −11.4 (NO
2
).
P
37.8 (d, CH
2
P, JPC = 53.8 Hz); 114.9 (C
, OPh); 127.0 (C
CH ); 136.7 (d, C , OPh, J = 10.1
3
, OPh); 118.3 (d, C
3
NMR (161.98 MHz, CDCl
3
): δ 105.7, 107.9, 108.6. IR (neat): OPh, JPC = 3.9 Hz); 122.9 (C
4
, P CH ); 128.5
νmax = 3202, 3065, 3028, 2964, 2924, 2874, 1619, 1589, 1510, (C , P
̲
̲
̲
̲
o
2
m
2
3
1
7
453, 1395, 1309, 1200, 1154, 1086, 1051, 1005, 963, 908, 846, Hz); 138.5 (C
64, 737, 703, 635, 623, 536 cm
5
2
, OPh); 139.6 (d, C
i
, P
̲
̲
2
, JPC = 14.7 Hz); 146.1
): δ
−1
15
.
Anal. calcd for (d, C
1
3
1
C H N O PS: C 63.42; H 5.99; N 6.16; P 6.81; S 7.05. Found: −317.3 (NH ); −10.8 (NO ). P NMR (161.98 MHz, CDCl ): δ
2
4
27
2
3
2
2
1
77
C 63.62; H 6.06; N 6.23; P 6.64; S 6.86.
O-(3-Aminophenyl) bis(2-phenylethyl)phosphinoselenoate CDCl
108.3 (+d-satellites, JPSe = 809.0 Hz). Se NMR (76.31 MHz,
1
3
): δ −237.4 (d, JPSe = 809.0 Hz). IR (neat): νmax = 3198,
H NMR 3064, 3027, 2922, 2858, 1619, 1589, 1510, 1451, 1397, 1310,
P); 2.95–3.14 (m, 1268, 1198, 1151, 1085, 1005, 960, 905, 842, 750, 701, 640, 581,
1
(
(
4
8
12h). Yield: 351 mg (82%); waxy product.
400.13 MHz, CDCl ): δ 2.49–2.61 (m, 4H, CH
); 3.89 (br s, 2H, NH ); 6.53 (d, 1H, H
3
2
3
−1
H, PhCH
̲
2
2
4
, OPh, JHH
=
23 2 3
467 cm . Anal. calcd for C22H N O PSe: C 55.82; H 4.90; N
4
.0 Hz); 6.57 (s, 1H, H , OPh); 6.58 (d, 1H, H , OPh, J = 8.2 5.92; P 6.54; Se 16.68. Found: C 55.99; H 4.96; N 5.98; P 6.36;
2
6
HH
3
3
Hz); 7.12 (dd, 1H, H
5
, OPh,
CH
C{ H} NMR (100.62 MHz, CDCl ): δ 29.5 (d, PhC
J
HH = 8.0 Hz,
); 7.32–7.36 (m, 4H, H
J
HH = 8.2 Hz); Se 16.53.
7
.22–7.29 (m, 6H, Ho,p, P
̲
̲
2
m
, P
̲
̲
2
).
O-(2-Amino-5-nitrophenyl) bis(2-phenylpropyl)phosphinose-
1
3
1
2
̲
3
2
PC
Org. Biomol. Chem.
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Organic & Biomolecular Chemistry
is a mixture of three stereoisomers in a ratio of 2.5 : 1.6 : 1 ( H
Paper
1
(d) Ł. Joachimiak and K. M. Błażewska, J. Med. Chem., 2018,
61, 8536–8562; (e) Á. Tajti and G. Keglevich, in
Organophosphorus Chemistry, ed. G. Keglevich, Boston: De
Gruyter, Berlin, 2018, pp. 53–65.
3
1
1
and P NMR data). H NMR (400.13 MHz, CDCl ): δ 1.16, 1.25,
3
3
3
3
1
.32, 1.44 (4 d, Me, JHH = 7.0 Hz, JHH = 6.9 Hz, JHH = 7.0 Hz,
3
JHH = 7.0 Hz); 1.49–1.55, 2.07–2.16, 2.34–2.71 (3 m, 4H,
CH P); 3.17–3.26, 3.33–3.50 (2 m, 2H, PhCH
̲
2 (a) Y. K. Kim, T. Livinghouse and Y. Horino, J. Am. Chem.
Soc., 2003, 125, 9560–9561; (b) D. Cauzzi, C. Graiff,
R. Pattacini, G. Predieri, A. Tiripicchio, S. Kahlal and
J.-Y. Saillard, Eur. J. Inorg. Chem., 2004, 1063–1072;
(c) D. B. G. Williams, S. J. Evans, H. de Bod,
M. S. Mokhadinyana and T. Hughes, Synthesis, 2009, 3106–
3112; (d) C. Popovici, I. Fernández, P. Oña-Burgos,
L. Roces, S. García-Granda and F. López Ortiz, Dalton
Trans., 2011, 40, 6691–6703.
3 (a) X. Song and M. Bochmann, J. Chem. Soc., Dalton Trans.,
1997, 2689–2692; (b) P. Oña Burgos, I. Fernández,
M. J. Iglesias, S. García-Granda and F. López Ortiz, Org.
Lett., 2008, 10, 537–540; (c) R. H. Crampton, S. El Hajjaji,
M. E. Fox and S. Woodward, Tetrahedron: Asymmetry, 2009,
20, 2497–2503.
4 B. Tang, B. Ding, K. Xu and L. Tong, Chem. – Eur. J., 2009,
15, 3147–3151.
5 (a) C.-S. Cho, S.-C. Fu, L.-W. Chen and T.-R. Wu, Polym. Int.,
1998, 47, 203–209; (b) Z. Jiang, D. Xu, X. Ma, J. Liu and
P. Zhu, Cellulose, 2019, 26, 5783–5796.
6 (a) F. Orsini, G. Sello and M. Sisti, Curr. Med. Chem., 2010,
17, 264–289; (b) P. Jeschke, Pest Manag. Sci., 2016, 72, 210–
225.
2
3
(3 br s, 2H, NH
2
); 6.52, 6.55, 6.61 (3 d, 1H, H
3
, OPh, JHH = 8.8
Hz); 7.16–7.37 (m, 10H, Ho,m,p, P
̲ ̲
HH
CH); 7.83, 7.85, 7.87, 7.88 (4
3
4
dd, 1H, H , OPh, J = 8.8 Hz, J = 2.5 Hz); 7.93, 8.02, 8.04
4
HH
4
4
(
(
6
3 dd, 1H, H , OPh, JHH = 2.5 Hz, JHH = 1.5 Hz). C{ H} NMR
100.62 MHz, CDCl
3
): δ 24.4, 24.5, 25.0, 25.2 (4 d, Me, JPC
3
3
3
1
3
1
5
6
C
3.9 Hz, J = 15.2 Hz, J = 13.5 Hz, J = 14.2 Hz); 35.4,
PC
PC
PC
2
2
6.0, 36.1, 36.3 (4 d, PhC
̲
2
.5 Hz, JPC = 1.0 Hz); 43.1, 44.2, 44.9, 45.1 (4 d, CH
1
1
1
6.5 Hz, J = 52.9 Hz, J = 52.1 Hz, J = 54.3 Hz, J
PC
PC
PC
4
4.6 Hz); 114.0, 114.2, 114.4 (C , OPh); 116.6, 117.8, 118.1 (3 d,
3
3
3
6
, OPh, JPC = 5.0 Hz, JPC = 4.2 Hz, JPC = 4.4 Hz); 122.2,
1
22.4 (C , OPh); 126.9, 127.1, 127.2, 128.4 (C , P
3
1
1
1
1
27.3, 127.5 (C
o
, P
, OPh,
̲
h
̲
CH); 128.9, 129.0, 129.1 (C
3
36.5 (2 d, C
2
J
PC = 9.9 Hz); 137.8, 138.0 (C
2
2
44.9, 145.1 (2 d, C , OPh, J = 4.3 Hz, J = 5.3 Hz); 145.6,
1
PC
PC
3
i
45.7, 145.9, 146.0 (4 d, C , P ̲h ̲C H, JPC = 14.5 Hz, JPC = 14.1
3
3
15
Hz,
JPC = 12.3 Hz,
J
PC = 15.7 Hz). N NMR (40.56 MHz,
3
1
CDCl ): δ −316.6 (NH ); −9.6 (NO ). P NMR (161.98 MHz,
CDCl
3
2
2
1
3
): δ 106.2 (+d-satellites, JPSe = 804.6 Hz); 109.7 (+d-satel-
1
1
lites, JPSe = 807.9 Hz); 110.0 (+d-satellites, JPSe = 804.1 Hz).
7
7
Se NMR (76.31 MHz, CDCl ): δ −227.9 (d, J
3
1
1
−
217.3 (d, JPSe = 804.6 Hz); −211.2 (d, JPSe = 804.1 Hz). IR
(
1
8
neat): νmax = 3198, 3065, 3027, 2964, 2924, 2874, 1618, 1588,
7 (a) D. V. Aleksanyan, V. A. Kozlov, Y. V. Nelyubina,
K. A. Lyssenko, L. N. Puntus, E. I. Gutsul, N. E. Shepel,
A. A. Vasil’ev, P. V. Petrovskii and I. L. Odinets, Dalton
Trans., 2011, 40, 1535–1546; (b) G. M. Dobrikov,
V. Valcheva, M. Stoilova-Disheva, G. Momekov,
P. Tzvetkova, A. Chimov and V. Dimitrov, Eur. J. Med.
Chem., 2012, 48, 45–56; (c) G. Bianchini, G. Strukul,
D. F. Wass and A. Scarso, RSC Adv., 2015, 5, 10795–10798.
508, 1452, 1393, 1309, 1198, 1153, 1086, 1051, 1005, 962, 908,
−1
45, 759, 736, 704, 643, 530, 487 cm . Anal. calcd for
PSe: C 57.49; H 5.43; N 5.59; P 6.18; Se 15.75.
24 27 2 3
C H N O
Found: C 57.68; H 5.50; N 5.66; P 6.00; Se 15.59.
Conflicts of interest
8
F. R. Atherton, H. T. Openshaw and A. R. Todd, J. Chem.
Soc., 1945, 660–663.
There are no conflicts to declare.
9
(a) S. S. Le Corre, M. Berchel, H. Couthon-Gourvès,
J.-P. Haelters and P.-A. Jaffrès, Beilstein J. Org. Chem., 2014,
Acknowledgements
1
0, 1166–1196; (b) Y. Ou, Y. Huang, Z. He, G. Yu, Y. Huo,
X. Li, Y. Gao and Q. Chen, Chem. Commun., 2020, 56, 1357–
360.
The main results were obtained using the equipment of the
Baikal Analytical Center for Collective use SB RAS. The
quantum chemical calculations were performed on the compu-
tational cluster “Academician V.M. Matrosov” of Irkutsk
Supercomputer Center SB RAS.
1
1
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