Solvent-free synthesis of 4-chalcogenophosphorylpyridines via SN HAr reaction of pyridines with secondary phosphine chalcogenides

Article abstract of DOI:10.1016/j.mencom.2018.11.005

Solvent- and catalyst-free synthesis of 4-chalcogenophosphorylpyridines by oxidative regioselective cross-coupling of pyridines with secondary phosphine chalcogenides using 1,3-diphenylprop-2-yn-1-one as a trigger and oxidant under mild conditions (70–75°C, 5.5–7 h) is reported.

Full text of DOI:10.1016/j.mencom.2018.11.005

Mendeleev
Communications
Mendeleev Commun., 2018, 28, 582–583
Solvent-free synthesis of 4-chalcogenophosphorylpyridines
via SHNAr reaction of pyridines with secondary phosphine chalcogenides
Pavel A. Volkov, Nina I. Ivanova, Kseniya O. Khrapova, Anton A. Telezhkin,
Tatyana N. Borodina, Nina K. Gusarova and Boris A. Trofimov*
A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 664033
Irkutsk, Russian Federation. Fax: +7 3952 419 346; e-mail: boris_trofimov@irioch.irk.ru
DOI: 10.1016/j.mencom.2018.11.005
Ph
Ph
R
X
O
+
+
P
Ph
N
Ph
H
Solvent- and catalyst-free synthesis of 4-chalcogenophos-
phorylpyridines by oxidative regioselective cross-coupling
of pyridines with secondary phosphine chalcogenides using
1,3-diphenylprop-2-yn-1-one as a trigger and oxidant under
mild conditions (70–75 °C, 5.5–7 h) is reported.
R = H, Me
X = O, S
Ph
X
Ph
70–75°C, 5.5–7 h
P
R
+
no solvent
and catalyst
Ph
Ph
O
N
up to 77%
Solvent-free organic synthesis now attracts a special attention as
one of the most promising approaches toward waste prevention and
environmental protection.1–8 During the last years, the solvent-
free green methodology has been successfully used in the
organophosphorus chemistry for the C–P bond formation.8–14
Of particular note is a crucial role of the concentration effect
in the solvent-free version of alkenes,9–11,13,14 alkynes8,13 and
aldehydes12 phosphorylation with H-phosphines and their chalco-
genides.
pyridines 4a–c in 62–77% yield (Scheme 1).† The secondary
product in this process was the expected chalcone 5. This solvent-
free procedure not only makes this process environmentally
benign, but also significantly (by 5–8 times) shortens the reaction
time and in some cases increases the products yield (Table 1).
Under studied conditions, bis(2-phenylethyl)phosphine selenide
2c did not react properly with pyridine, although the expected
4-[bis(2-phenylethyl)phosphoroselenoyl]pyridine 4d was formed
when the reaction was carried out in MeCN15 (see Table 1, entry 4).
Recently, we have reported15 the nucleophilic substitution
(SHNAr reaction) of the hydrogen atom in pyridines under the
action of secondary phosphine chalcogenides, phosphorus-centered
nucleophiles, in the presence of ynones as initiators (triggers) and
oxidants. The reaction proceeded in organic solvent (acetonitrile)
at a prolonged heating (70–75 °C, 20–70 h) and led to 4-chalco-
genophosphorylpyridines in 36–71% yield, wherein the ynones
were reduced to the corresponding E-enones. The secondary
phosphine chalcogenides could be easily prepared from styrene
and red phosphorus.16
Table 1 Solvent-free cross-coupling of pyridines 1a,b with secondary
phosphine chalcogenides 2a–c in the presence of ynone 3 and the known
data for the similar syntheses in MeCN.a
Phosphine
chalcogenide 2 time/h
Reaction
Isolated
yield (%)
Entry Pyridine 1
Product 4
6.0b (50c) 4a
1
1a
1b
1a
1a
2a
2a
2b
2c
77b (68c)
62b (64c)
75b (71c)
tracesb (40c)
2
3
4d
7.0b (35c) 4b
5.5b (34c) 4c
5.0b (24c) 4d
Here we report the improved procedure of such a reaction
under solvent-free conditions. In fact, pyridines 1a,b easily react
with bis(2-phenylethyl)phosphine oxide 2a or bis(2-phenyl-
ethyl)phosphine sulfide 2b in the presence of 1,3-diphenylprop-
2-yn-1-one 3 under mild conditions (70–75°C, 5.5–7 h) to afford
the corresponding 4-[bis(2-phenylethyl)chalcogenophosphoryl]-
a Conditions: 70–75°C, 1 (1.1 mmol), 2 (1.0 mmol), 3 (1.1 mmol). bReaction
time and product yield for solvent-free process. cReported data15 for the
reaction in MeCN. dBis(3-oxo-1,3-diphenylprop-2-en-1-yl) selenide, formed
from bis(2-phenylethyl)phosphine selenide 2c and ynone 3,17 was detected
(77Se NMR) in the reaction mixture (conversion of 2c was ~100%).
The 1H, 13C, 15N, 31P NMR spectra were recorded on Bruker DPX 400
†
and BrukerAV 400 spectrometers (400.13, 100.62, 40.56 and 161.98 MHz,
respectively) in CDCl3 solutions and referenced to HMDS (1H, 13C),
MeNO2 (15N) and H3PO4 (31P). The C, H, N microanalyses were performed
on a Flash EA 1112 Series elemental analyzer. The P, S content was
determined by the combustion method.
4-Chalcogenophosphorylpyridines 4a–c (general procedure). Pyridine
1a,b (1.1 mmol), secondary phosphine chalcogenide 2a,b (1.0 mmol)
and ynone 3 (1.1 mmol) were stirred under argon at 70–75°C for 5.5–7 h
(Table 1). After completion of the reaction (31P NMR monitoring), the
resulted mixture was purified by column chromatography on SiO2 (eluent
for 4a,b: ethylacetate; for 4c: toluene–Et2O, 1:2) to yield the individual
4-chalcogenophosphorylpyridine 4a–c as well as crude enone 5. The
latter was additionally purified by recrystallization from hexane.
1H, 13C, 15N and 31P NMR data for compounds 4a–c and 5 are in
accordance with the known data.15
Ph
R
O
X
70–75 °C
5.5–7 h
+
+
Ph
P
Ph
N
H
Ph
1a R = H
1b R = Me
2a X = O
2b X = S
3
2c X = Se
Ph
Ph
X
Ph
P
R
+
4a R = H, X = O
4b R = Me, X = O
4c R = H, X = S
4d R = H, X = Se
Ph
O
N
4a–d
Scheme 1
5
© 2018 Mendeleev Communications. Published by ELSEVIER B.V.
on behalf of the N. D. Zelinsky Institute of Organic Chemistry of the
Russian Academy of Sciences.
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Mendeleev Commun., 2018, 28, 582–583
not only to increase its environmental friendliness, but also to
significantly reduce the heating time. In this SNHAr reaction of
pyridines with secondary phosphine chalcogenides in the presence
of 1,3-diphenylprop-2-yn-1-one as a trigger and oxidant, the
corresponding chalcone is also formed. This enone is a valuable
building block for organic synthesis23 and biologically active
substances.24
N(1)
S(2)
P(1)
P(2)
S(1)
This study was performed using the facilities of the Baikal
Joint Analytical Center, Siberian Branch, Russian Academy of
Sciences.
N(2)
Figure 1 Compound 4c in thermal vibration ellipsoids at 50% probability.
References
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scopy, elemental analysis, and X-ray diffraction analysis {for
4-[bis(2-phenylethyl)phosphorothioyl]pyridine 4c, Figure 1}.‡
Compound 4c crystallizes in colourless prisms of the mono-
clinic system, P21/c centrosymmetric space group. The independent
part of the elementary crystal cell contains two molecules, differing
in spatial arrangement of the phenyl and pyridine rings. According
to X-ray analysis data (see Figure 1), P atom has a pyramidal
coordination, the length of the P–S bond is 1.9591(5) Å, and
those of the P–C bonds are 1.816(1)–1.824(1) Å. The valence angles
S–P–C [112.22(5)–114.10(5)°] and C–P–C [103.96(7)–106.28(7)°]
differ from the ideal tetrahedral angle (109.5°). The lengths of the
C–C alkyl bonds are 1.532(2)–1.539(2) Å, those of the C–C bonds
in the phenyl rings are 1.376(3)–1.395(2) Å. In the pyridine ring,
the lengths of the C–C bonds are 1.385(2)–1.395(2) Å and those
of the C–N bonds are 1.336(2)–1.341(2) Å.
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4-[Bis(2-phenylethyl)phosphoryl]pyridine 4a. Yield 258 mg (77%),
yellow powder, mp 80–81°C (lit.,15 mp 81–82°C). 31P NMR, d: 37.5.
Found (%): C, 75.39; H, 6.58; N, 4.09; P, 9.08. Calc. for C21H22NOP (%):
C, 75.21; H, 6.61; N, 4.18; P, 9.24.
4-[Bis(2-phenylethyl)phosphoryl]-3-methylpyridine 4b. Yield 217 mg
(62%), waxy product. 31P NMR, d: 39.6. Found (%): C, 75.58; H, 6.79;
N, 4.11; P, 8.73. Calc. for C22H24NOP (%): C, 75.62; H, 6.92; N, 4.01;
P, 8.86.
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4-[Bis(2-phenylethyl)phosphorothioyl]pyridine 4c.Yield 264 mg (75%),
crystalline compound (from hexane), mp 84–85°C (lit.,15 mp 83–84°C).
31P NMR, d: 45.7. Found (%): C, 71.63; H, 6.37; N, 3.92; P, 8.67; S, 8.89.
Calc. for C21H22NPS (%): C, 71.77; H, 6.31; N, 3.99; P, 8.81; S, 9.12.
‡
Crystal data for 4c. Data were collected on a Bruker D8Venture PHOTON
100 CMOS diffractometer with MoKa radiation (l = 0.71073 Å) using
the j- and w-scan techniques. The structures were solved and refined by
direct methods using SHELX.18 Data were corrected for absorption effects
using the multi-scan method (SADABS). All non-hydrogen atoms were
refined anisotropically using SHELX.18 The coordinates of the hydrogen
atoms were calculated from geometrical positions. The crystal of C21H22NPS
is monoclinic, space group P21/c, a = 38.2260(18), b = 9.0661(4) and
c = 10.8855(5) Å, b = 97.3460(10)°, V = 3741.5(3) Å3, Z = 8, reflections
collected 91206, of which 9010 unique reflections (Rint = 0.0400) were
used in all calculations. The final parameters are R1 = 0.0383, wR2 = 0.0951
[I > 2s(I)] and R1 = 0.0456, wR2 = 0.0992 (all data). GOOF = 1.076.
Completeness 99.8%.
CCDC 1837673 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via http://www.ccdc.cam.ac.uk.
Received: 15th May 2018; Com. 18/5578
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