Synthesis of 1-Amino-2,5-dihydro-1H-phosphole 1-oxides and their N-phosphinoyl derivatives, bis(2,5-dihydro-1 H -phosphol-1-yl)amine P, P-dioxides

Article abstract of DOI:10.1055/s-0032-1316830

Depending on the molar ratio of the reactants and on the order of mixing, the reactions of a series of primary amines with 1-chloro-2,5-dihydro-1H- phosphole 1-oxides prepared in situ from the corresponding hydroxy- dihydrophosphole oxides afforded 1-amino-2,5-dihydro-1H-phosphole 1-oxides, or their N-phosphinoyl derivatives, bis(2,5-dihydro-1H-phosphol-1-yl)amine P,P-dioxides. The latter family of P-heterocycles could also be synthesized by the reaction of 1-amino-2,5-dihydro-1H-phosphole oxides with chloro-dihydrophosphole oxides.

Full text of DOI:10.1055/s-0032-1316830

PAPER
▌199
paper
Synthesis of 1-Amino-2,5-dihydro-1H-phosphole 1-Oxides and Their
N-Phosphinoyl Derivatives, Bis(2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxides
Amino-dihydrophosphole Oxides and Their N-Phosphinoyl Derivatives
Nóra Zsuzsa Kiss,a András Simon,b László Drahos,c Krzysztof Huben,d Stefan Jankowski,d György Keglevich*a
a
Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, Műegyetem rkp.3, 1521 Budapest,
Hungary
b
Department of Inorganic and Analytical Chemistry, Budapest University of Technology and Economics, Műegyetem rkp.3, 1521 Budapest,
Hungary
c
Hungarian Academy of Sciences, Chemical Research Center, Pusztaszeri út 59-67, 1525 Budapest, Hungary
d
Institute of Organic Chemistry, Faculty of Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Łódź, Poland
Fax +36(1)4633648; E-mail: gkeglevich@mail.bme.hu
Received: 29.10.2012; Accepted after revision: 29.11.2012
by the senior author of this paper and co-workers.22–24 The
Michael reaction of 1-phenyl-2,3-dihydrophosphole ox-
ide and diphenylphosphine oxide provides a 1-phosphino-
yl-2,3,4,5-tetrahydro-1H-phosphole oxide25 that is the
Abstract: Depending on the molar ratio of the reactants and on the
order of mixing, the reactions of a series of primary amines with 1-
chloro-2,5-dihydro-1H-phosphole 1-oxides prepared in situ from
the corresponding hydroxy-dihydrophosphole oxides afforded 1-
amino-2,5-dihydro-1H-phosphole 1-oxides, or their N-phosphinoyl precursor of LUPHOS.26 Complexation of LUPHOS with
platinum gave a cis-chelate complex.27
derivatives, bis(2,5-dihydro-1H-phosphol-1-yl)amine P,P′-diox-
ides. The latter family of P-heterocycles could also be synthesized
by the reaction of 1-amino-2,5-dihydro-1H-phosphole oxides with
chloro-dihydrophosphole oxides.
1-Amino-2,5-dihydrophosphole oxides are important in-
termediates.28–30 On one hand, the trichlorosilane reduc-
tion of such species furnishes valuable 1-chloro-2,5-
Key words: phosphorus, heterocycles, amides, phosphorylation,
spectroscopy
dihydro-1H-phospholes.28 On the other hand, their reac-
tion with dichlorocarbene results in the formation of
versatile
intermediates,
3-amino-3-phosphabicyc-
lo[3.1.0]hexane 3-oxides.29,30 A number of 1-amino-2,5-
dihydrophosphole oxide derivatives28,30–38 are known
from the literature. The basic method for the preparation
of these species involves the reaction of the corresponding
halogeno-dihydrophosphole oxides, almost exclusively
chlorides, with secondary amines,31–33 or with primary
amines.30,34–37 In this paper, the synthesis of new N-mono-
substituted 1-amino-2,5-dihydro-1H-phosphole 1-oxides
and their N-phosphinoyl derivatives, bis(2,5-dihydro-1H-
phosphol-1-yl)amine P,P′-dioxides is described. The lat-
ter series is a less studied family of compounds. Two anal-
ogous derivatives have been described, but no yields and
spectral characterization was provided.36
The 2,5-dihydro- or 2,3-dihydro-1H-phosphole 1-oxides
(2- and 3-phospholene 1-oxides), easily available by the
McCormack cycloaddition and subsequent functionaliza-
tion, form a representative group of P-heterocycles.1–4
Quin and Mathey were the first chemists to explore
systematically the field of phosphole derivatives.1,3
Pietrusiewicz et al. elaborated novel methods for the mod-
ification of dihydrophosphole oxides based on C-alkyl-
ation, annulation, and epoxidation.5–9 Yamashita
synthesized ‘phospha-sugars’ on the basis of 2,3- and 3,4-
dihydrophosphole oxides.10–13 Keglevich et al. developed
the ring opening of 2,5-dihydro-1H-phosphole oxides. Di-
chlorocarbene addition to the double bond of 2,5-dihydro-
1H-phosphole oxides afforded 6,6-dichloro-3-phosphabi-
cyclo[3.1.0]hexane 3-oxides that were converted into 1,2-
dihydrophosphinine oxides by thermolysis.14–16 1,2-Dihy-
drophosphinine oxides are versatile intermediates in the
preparation of more- and less-saturated phosphinine de-
rivatives.17,18 P-Heterocycles with a tervalent phosphorus
atom may be novel ligands in transition-metal complex-
es.19,20 These complexes may include optically active 2,5-
dihydro-1H-phosphole ligands,21 their precursors are the
corresponding optically active 2,5-dihydro-1H-phosphole
oxides obtained by resolution using methods developed
In the first step of our syntheses, 1-hydroxy-2,5-dihydro-
1H-phosphole 1-oxides 1 and 2 were converted into the
corresponding 1-chloro derivatives 3 and 4 by reaction
with thionyl chloride in dichloromethane at 26 °C for 24
hours.29 Adding one equivalent of the primary amine,
such as hexylamine, cyclohexylamine, or benzylamine, to
the equimolar mixture of chloro-dihydrophosphole oxide
3 and triethylamine in toluene resulted in a mixture con-
taining the expected 1-amino-2,5-dihydro-1H-phosphole
oxides 5c–e as minor products in 35–46% yields (with
δP = 60.7–63.5). The major components, obtained in 54–
65% yields, appeared at δP = 66.8–68.9 and proved to be
bis(2,5-dihydro-1H-phosphol-1-yl)amine P,P′-dioxides
6c–e after isolation and identification (Scheme 1). Next
we tried to influence the product composition by adding
the toluene solution of the chloro-dihydrophosphole oxide
SYNTHESIS 2013, 45, 0199–0204
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DOI: 10.1055/s-0032-1316830; Art ID: SS-2012-T0862-OP
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200
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3 to an equimolar mixture of the corresponding primary The reason for this phenomenon is that, in these cases, the
amine and triethylamine. This had a dramatic impact on P1, C2, C3, and C3–CH3 atoms of the two hetero rings are
the product composition and the expected 1-amino-2,5-di- chemically equivalent, but magnetically not equivalent.
hydro-1H-phosphole 1-oxides 5c–e were formed as al- Considering the natural abundance (1.1%) of the 13C at-
most exclusive products (Scheme 1). This method was oms, the multiplicity of these atoms may be described by
then applied to the synthesis of other amino-dihydrophos- the higher order spin system AA′X, where A is P, and X
phole oxides 5a and 5b by the reaction of chloro-dihydro- is C.39 The multiplets were simplified to singlets on 31P
phosphole oxide 3 with butylamine and isobutylamine decoupling. The appearance of the signals for C3 and C3-
(Scheme 1).
CH3 is shown in Figure 1, A. The multiplicity of the sig-
nals in the 13C NMR spectra of bis(dihydrophospho-
lyl)amine dioxides 6 including two 3-methyl-2,5,-
dihydro-1H-phosphol-1-yl units was similar, but the
peaks were doubled as a consequence of the P-chiral cen-
ters. The 31P decoupling again simplified the spectrum
(Figure 1, B). For more information, the multiplicity of C2
is also shown in Figure 1. The doublet became a singlet on
31P decoupling. As a consequence of the P-chirality, prod-
ucts 6 were obtained as 1:1 mixtures of the racemic
(RR/SS) and the meso (RS/SR) diastereomers. A good il-
lustration of the isomeric composition of bis(dihydro-
phospholyl)amine dioxides 6 is shown by the pair lines for
C2 and C3.
The 1-amino-2,5-dihydro-1H-phosphole 1-oxides 5a–e
were obtained in 76–88% yields after purification by col-
umn chromatography and were characterized by 31P, 13C,
and 1H NMR, as well as mass spectral data.
Me
R1
R1
Me
SOCl2
CH2Cl2
26 °C
P
P
O
Cl
O
OH
1 R1 = H
3 R1 = H
4 R1 = Me
2 R1 = Me
R2NH2
PhMe
Et3N
R1
Me
R1
Me
Me
R1 = H
(from 3)
4
1
P
3
5
4
5
3
2
2
1
P
NR2
P
O
O
O
NHR2
6 R1 = H
5a R2 = n-Bu
5b R2 = i-Bu
5c R2 = n-Hex
5d R2 = c-Hex
5e R2 = Bn
7 R1 = Me
5f R2 = PhCH2CH2
5g R2 = Ph
Scheme 1
Then we returned to the original method, in which the
amines, including also 2-phenylethylamine, aniline, and
4-methoxyaniline were added to a toluene solution of the
1-chloro-2,5-dihydro-1H-phosphole 1-oxide (3) and an
equivalent of triethylamine, but the quantity of the amine
was reduced to 0.5 equivalent. These experiments led to
bis(2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-oxides
6a–g as almost exclusive products (Scheme 1). The di-
methyl derivatives 7a and 7e were synthesized in a similar
way from chloro-dihydrophosphole oxide 4 (Scheme 1).
The bis(2,5-dihydro-1H-phosphol-1-yl)amine P,P′-diox-
ides 6a–g and 7a,e were obtained in 72–95% yields after
purification by chromatography. The structures of the
products were supported by 31P, 13C, and 1H NMR, as well
as mass spectral parameters.
In the 13C NMR spectra of bis(dihydrophospholyl)amine
dioxides 7 comprising two 3,4-dimethyl-2,5-dihydro-1H-
phosphol-1-yl moieties, the C3 and the C3–CH3 carbon at-
oms appeared as a special multiplet, where the intensity of
the middle peak was much lower than the other two peaks.
Figure 1 Segments from the 13C NMR spectra of bis(2,5-dihydro-
1H-phosphol-1-yl)amine P,P′-dioxides 6 and 7
It seemed to be reasonable to try to prepare bis(dihydro-
phospholyl)amine dioxides 6c–e by the reaction of 1-ami-
no-2,5-dihydro-1H-phosphole 1-oxides 5c–e with 1-
chloro-2,5-dihydro-1H-phosphole 1-oxide 3. In accord
with expectation, the reactions were complete after reflux
for four hours in toluene. The bis(dihydrophospho-
lyl)amine dioxides 6c–e were obtained in 58–83% yields
after workup including flash chromatography (Scheme 2).
Synthesis 2013, 45, 199–204
© Georg Thieme Verlag Stuttgart · New York

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Amino-dihydrophosphole Oxides and Their N-Phosphinoyl Derivatives
201
1-(Hexylamino)-3-methyl-2,5-dihydro-1H-phosphole 1-Oxide
Et3N
+
3
5c–e
6c–e
(5c)
PhMe
reflux, 4 h
Yellowish oil; yield: 2.0 g (82%).
IR (film): 2930, 1643, 1200, 1166, 768 cm–1.
Scheme 2
3
1H NMR (300 MHz, CDCl3): δ = 0.85 (t, J(HH) = 6.2 Hz, 3 H,
CH3CH2), 1.18–1.35 (m, 6 H, 3 CH2), 1.41–1.55 (m, 2 H, CH2),
1.76 (s, 3 H, C3–CH3), 2.18–2.57 (m, 5 H, 2 PCH2, NH), 2.81–2.96
(m, 2 H, NCH2), 5.48 (br d, 3J(PH) = 33.4 Hz, 1 H, CH=).
13C NMR (75.5 MHz, CDCl3): δ = 13.7 (CH3CH2), 20.4 (3J = 12.1
Hz, C3–CH3), 22.3 (CH3CH2), 26.2 (CH2), 31.2 (CH2), 31.8
(3J = 6.2 Hz, NCH2CH2), 31.9 (1J = 82.0 Hz, C5), 34.8 (1J = 85.5
Hz, C2), 40.4 (NCH2), 120.5 (2J = 9.6 Hz, C4), 136.4 (2J = 15.2 Hz,
C3).
31P, 13C, and 1H NMR spectra were collected on a Bruker Avance-
300 instrument operating at 121.5, 75.5, and 300 MHz, respectively.
1
31P, 13C, and H NMR spectra of compounds 6a and 7a were ob-
tained on a Bruker Avance-700 spectrometer at 283.4, 176, and 700
MHz, respectively, while 13C {1H,31P} decoupled NMR spectra
were recorded on a Bruker Avance-500 instrument at 125.8 MHz.
The exact mass measurements were performed using a Q-TOF Pre-
mier mass spectrometer in positive electrospray mode.
31P NMR (121.5 MHz, CDCl3): δ = 63.1.
HRMS (ESI): m/z [M + H]+ calcd for C11H23NOP: 216.1517; found:
1-Amino-3-methyl-2,5-dihydro-1H-phosphole 1-Oxide 5; Gen-
eral Procedure
216.1527.
To 1-hydroxy-3-methyl-2,5-dihydro-1H-phosphole 1-oxide (1, 1.5
g, 11.4 mmol) in anhyd CH2Cl2 (5 mL) was added SOCl2 (1 mL,
13.8 mmol) and the mixture was stirred at 26 °C for 24 h. The sol-
vent was evaporated and the volatile residues were removed under
high vacuum. The 1-chloro-3-methyl-2,5-dihydro-1H-phosphole 1-
oxide (3, 1.70 g, ~100%) so obtained was taken up in anhyd toluene
(3 mL) and the resulting soln was added dropwise to a mixture of
primary amine (BuNH2: 1.14 mL, i-BuNH2: 1.14 mL,
Me(CH2)5NH2: 1.5 mL, CyNH2: 1.4 mL, Ph(CH2)2NH2: 1.44 mL,
BnNH2: 1.3 mL, PhNH2: 1.0 mL, 4-MeOC6H4NH2: 1.32 mL; 11.4
mmol) and Et3N (1.6 mL, 11.4 mmol) in toluene (3 mL) at 60 °C.
The contents of the flask were stirred at reflux for 2 h. The amine
hydrochloride salt was removed by filtration and the filtrate evapo-
rated. The crude product was purified by column chromatography
(silica gel, 3% MeOH–CHCl3) to afford amino-dihydrophosphole
oxide 5.
1-(Cyclohexylamino)-3-methyl-2,5-dihydro-1H-phosphole
1-Oxide (5d)
Yellowish oil; yield: 2.1 g (85%).
IR (film): 2931, 1646, 1200, 1165, 765 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.76 (s, C3–CH3) overlapped by
1.02–2.00 (m, 5 CH2) (total 13 H), 2.15–2.60 (m, 5 H, NH, 2 PCH2),
2.94–3.14 (m, 1 H, CH), 5.48 (br d, 3J(PH) = 37.1 Hz, 1 H, CH=).
13C NMR (75.5 MHz, CDCl3): δ = 20.5 (3J = 12.1 Hz, C3–CH3),
24.9 (C3′)*, 25.2 (C4′), 33.1 (1J = 82.2 Hz, C5), 36.0 (1J = 85.7 Hz,
C2), 36.1 (3J = 4.0 Hz, C2′)*, 49.9 (C1′), 120.5 (2J = 9.7 Hz, C4),
136.4 (2J = 15.2 Hz, C3); * interchangeable.
31P NMR (121.5 MHz, CDCl3): δ = 60.7.
HRMS (ESI): m/z [M + H]+ calcd for C11H21NOP: 214.1361; found:
214.1369.
1-(Butylamino)-3-methyl-2,5-dihydro-1H-phosphole 1-Oxide
1-(Benzylamino)-3-methyl-2,5-dihydro-1H-phosphole 1-Oxide
(5a)
(5e)
Yellowish oil; yield: 1.8 g (85%).
Dense, yellowish oil; yield: 1.9 g (76%).
IR (film): 2932, 1644, 1201, 1161, 770 cm–1.
IR (film): 2935, 1640, 1206, 1160, 766 cm–1.
3
1H NMR (300 MHz, CDCl3): δ = 0.91 (t, J(HH) = 7.2 Hz, 3 H,
1H NMR (300 MHz, CDCl3): δ = 1.76 (s, 3 H, C3–CH3), 2.18–2.62
(m, 4 H, 2 PCH2), 3.01–3.16 (m, 1 H, NH), 4.08–4.20 (m, 2 H,
NHCH2), 5.51 (br d, 3J(PH) = 33.6 Hz, 1 H, CH=), 7.22–7.38 (m, 5
H, Ar).
CH3CH2), 1.28–1.42 (m, 2 H, CH2), 1.44–1.58 (m, 2 H, CH2), 1.79
(s, 3 H, C3–CH3), 2.12–2.60 (m, 5 H, 2 PCH2, NH), 2.86–3.00 (m,
2 H, NCH2), 5.51 (br d, 3J(PH) = 33.0 Hz, 1 H, CH=).
13C NMR (75.5 MHz, CDCl3): δ = 13.6 (CH3CH2), 19.8 (CH3CH2),
20.6 (3J = 12.1 Hz, C3–CH3), 32.1 (1J = 82.0 Hz, C5), 34.1 (3J = 6.2
Hz, NCH2CH2), 35.0 (1J = 85.5 Hz, C2), 40.3 (2J = 1.8 Hz, NCH2),
120.6 (2J = 9.7 Hz, C4), 136.6 (2J = 15.2 Hz, C3).
13C NMR (75.5 MHz, CDCl3): δ = 20.5 (3J = 12.1 Hz, C3–CH3),
32.2 (1J = 81.8 Hz, C5), 35.0 (1J = 85.3 Hz, C2), 44.2 (NCH2), 120.6
(2J = 9.8 Hz, C4), 127.3 (C2′,* C4′), 128.5 (C3′)*, 136.6 (2J = 15.3
Hz, C3), 139.6 (3J = 5.8 Hz, C1′); * interchangeable.
31P NMR (121.5 MHz, CDCl3): δ = 63.2.
31P NMR (121.5 MHz, CDCl3): δ = 63.5.
HRMS (ESI): m/z [M + H]+ calcd for C9H19NOP: 188.1204; found:
HRMS (ESI): m/z [M + H]+ calcd for C12H17NOP: 222.1048; found:
188.1210.
222.1051.
1-(Isobutylamino)-3-methyl-2,5-dihydro-1H-phosphole
1-Oxide (5b)
Bis(2,5-dihydro-1H-phosphol-1-yl)amine P,P′-Dioxides 6 and
7; General Procedure
Yellowish oil; yield: 1.9 g (88%).
To 1-hydroxy-3-methyl-2,5-dihydro-1H-phosphole 1-oxide (1, 0.5
g, 3.8 mmol) in anhyd CH2Cl2 (3 mL) was added SOCl2 (0.35 mL,
4.7 mmol) and the mixture was stirred at 26 °C for 24 h. Then sol-
vent was evaporated and the volatile components were removed un-
der vacuum. The 1-chloro-3-methyl-2,5-dihydro-1H-phosphole 1-
oxide (3, 0.57 g, ~100%) so obtained was taken up in anhyd toluene
(5 mL) and Et3N (0.53 mL, 3.8 mmol) was added. Then the primary
amine (BuNH2: 0.19 mL, i- BuNH2: 0.19 mL, Me(CH2)5NH2: 0.25
mL, CyNH2: 0.22 mL, Ph(CH2)2NH2: 0.24 mL, BnNH2: 0.20 mL,
PhNH2: 0.17 mL, 4-MeOC6H4NH2: 0.22 mL; 1.9 mmol) was added
and the contents of the flask were stirred at reflux for 6 h. The amine
hydrochloride salt was removed by filtration and the filtrate evapo-
rated. The crude product so obtained was purified by column chro-
matography (silica gel, 3% MeOH–CHCl3) to afford bis(2,5-
IR (film): 2931, 1643, 1200, 1164, 768 cm–1.
3
1H NMR (300 MHz, CDCl3): δ = 0.89 [d, J(HH) = 6.7 Hz, 6 H,
CH(CH3)2], 1.63–1.70 (m, 1 H, CH), 1.76 (s, 3 H, C3–CH3), 2.22–
2.56 (m, 5 H, 2 PCH2, NH), 2.67–2.74 (m, 2 H, NCH2), 5.49 (br d,
3J(PH) = 33.5 Hz, 1 H, CH=).
13C NMR (75.5 MHz, CDCl3): δ = 19.8 [CH(CH3)2], 20.6 (3J = 12.1
Hz, C3–CH3), 30.0 (3J = 6.2 Hz, CH), 32.1 (1J = 82.0 Hz, C5), 34.9
(1J = 85.5 Hz, C2), 48.1 (2J = 2.0, NCH2), 120.6 (2J = 9.7 Hz, C4),
136.6 (2J = 15.2 Hz, C3).
31P NMR (121.5 MHz, CDCl3): δ = 63.6.
HRMS (ESI): m/z [M + H]+ calcd for C9H19NOP: 188.1204; found:
188.1205.
© Georg Thieme Verlag Stuttgart · New York
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202
N. Z. Kiss et al.
PAPER
dihydro-1H-phosphol-1-yl)amine derivatives 6. The dimethyl de-
rivatives 7 were prepared in a similar way, starting from 1-hydroxy-
3,4-dimethyl-2,5-dihydro-1H-phosphole 1-oxide (2, 0.55 g, 3.8
mmol) via intermediate 1-chloro-3,4-dimethyl-2,5-dihydro-1H-
phosphole 1-oxide (4).
Cyclohexylbis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (6d)
Slightly yellowish oil; yield: 0.48 g (78%).
IR (film): 2932, 1648, 1231, 1182, 802 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.01–1.34 (m, 4 H, CH2), 1.70–
1.85, 1.81 (s, C3–CH3), overlapped by 1.70–1.85 (m, CH2) (total 10
H), 2.30–2.88 (m, 11 H, 4 PCH2, NCH, CH2), 5.56 (br d,
3J(PH) = 36.5 Hz, 2 H, 2 CH=).
13C NMR (75.5 MHz, CDCl3): δ = 20.6 (m, C3–CH3), 24.8 (C4′′),
27.0 (C3′′), 33.1 (t, 3J = 7.3 Hz, C2′′), 35.3 (d, 1J = 78.5 Hz, C5), 37.9
(d, 1J = 78.5 Hz, C2), 58.4 (C1′′), 120.6 (m, C4), 136.7 (m, C3).
The following products were thus prepared:
Butylbis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (6a)
Slightly yellowish oil; yield: 0.54 g (95%).
IR (film): 2935, 1648, 1225, 1183, 781 cm–1.
3
1H NMR (700 MHz, CDCl3): δ = 0.90 (t, J(HH) = 7.4 Hz, 3 H,
31P NMR (121.5 MHz, CDCl3): δ = 64.6.
HRMS (ESI): m/z [M + H]+ calcd for C16H28NO2P2: 328.1595;
CH3CH2), 1.21–1.32 (m, 2 H, CH2), 1.58–1.70 (m, 2 H, CH2), 1.81
(s, 6 H, 2 C3–CH3), 2.41–2.79 (m, 8 H, 4 PCH2), 3.04–3.15 (m, 2 H,
NCH2), 5.57 (br d, 3J(PH) = 35.9 Hz, 2 H, 2 CH=).
found: 328.1606.
13C NMR (176 MHz, CDCl3) {1H}: δ = 13.9 (CH3CH2), 20.4
Benzylbis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (6e)
(CH3CH2), 20.8 (m, C3–CH3), 34.2 (NCH2CH2), 34.55 (d, 1J = 80.0
1
1
Hz) and 34.61 (d, J = 80.0 Hz) (C5), 37.27 (d, J = 83.6 Hz) and
37.32 (d, 1J = 83.6 Hz) (C2), 44.2 (NCH2), 120.8 (m, C4), 136.9 (m,
C3).
Dense, slightly yellowish oil; yield: 0.60 g (95%).
IR (film): 2936, 1647, 1232, 1183, 779 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.76 (s, 6 H, 2 C3–CH3), 2.40–
2.82 (m, 8 H, 4 PCH2), 4.30–4.63 (m, 2 H, NCH2), 5.55 (br d,
3J(PH) = 36.3 Hz, 2 H, 2 CH=), 7.24–7.38 (m, 5 H, Ar).
13C NMR (125.8 MHz, CDCl3) {1H, 31P}: δ = 13.9 (CH3CH2), 20.4
(CH3CH2), 20.8 (C3–CH3), 34.2 (NCH2CH2), 34.55 and 34.61 (C2),
37.27 and 37.32 (C5), 44.2 (NCH2), 120.76 and 120.80 (C4), 136.88
and 136.92 (C3).
31P NMR (283.4 MHz, CDCl3): δ = 66.97 and 66.99.
HRMS (ESI): m/z [M + H]+ calcd for C14H26NO2P2: 302.1439;
3
13C NMR (75.5 MHz, CDCl3): δ = 20.4 (m, J = 13 Hz, C3–CH3),
33.94 (1J = 79.5 Hz) and 33.97 (1J = 79.4 Hz) (C5), 36.66 (1J = 83.1
Hz) and 36.70 (1J = 83.1 Hz) (C2), 46.18 (NCH2), 120.43 and
120.50 (m, 2J = 11 Hz, C4), 126.5 (C2′′)*, 127.5 (C4′′), 128.6 (C3′′)*,
136.6 (m, 2J = 17 Hz, C3), 138.0 (C1′′); * interchangeable.
found: 302.1448.
31P NMR (121.5 MHz, CDCl3): δ = 68.85 and 68.87.
HRMS (ESI): m/z [M + H]+ calcd for C17H24NO2P2: 336.1282;
Isobutylbis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (6b)
Slightly yellowish oil; yield: 0.30 g (53%).
found: 336.1288.
IR (film): 2937, 1647, 1229, 1184, 779 cm–1.
Bis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)(phenyl-
ethyl)amine P,P′-Dioxide (6f)
Slightly yellowish oil; yield: 0.61 g (93%).
IR (film): 2936, 1647, 1231, 1182, 763 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.81 (s, 6 H, 2 C3–CH3), 2.36–
2.78 (m, 8 H, 4 PCH2), 2.94–3.04 (m, 2 H, NCH2CH2), 3.18–3.42
(m, 2 H, NCH2), 5.57 (br d, 3J(PH) = 36.2 Hz, 2 H, 2 CH=), 7.13–
7.34 (m, 5 H, Ar).
3
1H NMR (300 MHz, CDCl3): δ = 0.93 [d, J(HH) = 6.7 Hz, 6 H,
(CH3)2CH], 1.81 (s, 6 H, 2 C3–CH3), 1.90–2.02 (m, 1 H, CH), 2.35–
2.84 (m, 8 H, 4 PCH2), 2.93–3.08 (m, 2 H, NCH2), 5.57 (br d,
3J(PH) = 36.0 Hz, 2 H, 2 CH=).
13C NMR (75.5 MHz, CDCl3): δ = 19.7 [CH(CH3)2], 20.4 (m,
3J = 13 Hz, C3–CH3), 29.1 (CH), 34.25 (1J = 80.1 Hz) and 34.34
(1J = 80.2 Hz) (C5), 36.98 (1J = 83.8 Hz) and 37.07 (1J = 83.8 Hz)
(C2), 50.7 (NCH2), 120.3 (m, 2J = 11 Hz, C4), 136.3 (m, 2J = 16 Hz,
C3).
3
13C NMR (75.5 MHz, CDCl3): δ = 20.3 (m, J = 13 Hz, C3–CH3),
34.18 (1J = 79.6 Hz) and 34.21 (1J = 79.5 Hz) (C5), 36.82 (1J = 83.4
Hz) and 36.86 (1J = 83.3 Hz) (C2), 38.0 (NCH2CH2), 45.5 (NCH2),
31P NMR (121.5 MHz, CDCl3): δ = 67.04 and 67.07.
HRMS (ESI): m/z [M + H]+ calcd for C14H26NO2P2: 302.1439;
2
120.37 and 120.41 (m, J = 11 Hz, C4), 126.6 (C4′′), 128.5 (C2′′)*,
128.7 (C3′′)*, 136.45 and 136.49 (m, 2J = 16 Hz, C3), 138.0 (C1′′);
found: 302.1447.
* interchangeable.
31P NMR (121.5 MHz, CDCl3): δ = 67.6.
HRMS (ESI): m/z [M + H]+ calcd for C18H26NO2P2: 350.1439;
found: 350.1447.
Hexylbis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (6c)
Slightly yellowish oil; yield: 0.34 g (54%).
IR (film): 2930, 1646, 1233, 1184, 779 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.86 (t, J(HH) = 6.6 Hz, 3 H,
CH3CH2), 1.20–1.29 (m, 6 H, CH2), 1.56–1.72 (m, 2 H, CH2), 1.81
(s, 6 H, 2 C3–CH3), 2.36–2.81 (m, 8 H, 4 PCH2), 2.98–3.18 (m, 2 H,
NCH2), 5.57 (br d, 3J(PH) = 35.9 Hz, 2 H, 2 CH=).
3
Bis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)phenylamine
P,P′-Dioxide (6g)
Slightly yellowish oil; yield: 0.44 g (72%).
IR (film): 2935, 1650, 1231, 1186, 774 cm–1.
13C NMR (75.5 MHz, CDCl3): δ = 13.7 (CH3CH2), 20.4 (m, C3–
CH3), 22.3 (CH3CH2), 26.4 (CH2), 31.0 (CH2), 31.6 (NCH2CH2),
1H NMR (300 MHz, CDCl3): δ = 1.66 (s, 6 H, 2 C3–CH3), 2.42–
2.82 (m, 8 H, 4 PCH2), 5.40 (br d, 3J(PH) = 34.9 Hz, 2 H, 2 CH=),
7.29–7.44 (m, 5 H, Ar).
1
34.16 (d, J = 80.0 Hz) and 34.20 (d, 1J = 80.0 Hz) (C5), 36.87 (d,
1J = 83.6 Hz) and 36.91 (d, 1J = 83.6 Hz) (C2), 44.0 (NCH2), 120.4
3
(m, C4), 136.5 (m, C3).
31P NMR (121.5 MHz, CDCl3): δ = 66.67 and 66.68.
HRMS (ESI): m/z [M + Na]+ calcd for C16H29NO2NaP2: 352.1571;
found: 352.1573.
13C NMR (75.5 MHz, CDCl3): δ = 20.2 (m, J = 13 Hz, C3–CH3),
33. 4 (1J = 82.2 Hz) (C5), 36.1 (1J = 85.9 Hz) (C2), 120.3 (m, 2J = 12
3
Hz, C4), 128.3 (br s, C4′′), 128.8 (t, J = 3.0 Hz, C2′′), 130.0 (br s,
C3′′), 136.4 (m, 2J = 18 Hz, C3), 139.1 (br s, C1′′).
31P NMR (121.5 MHz, CDCl3): δ = 65.8.
Synthesis 2013, 45, 199–204
© Georg Thieme Verlag Stuttgart · New York

PAPER
Amino-dihydrophosphole Oxides and Their N-Phosphinoyl Derivatives
203
HRMS (ESI): m/z [M + H]+ calcd for C16H22NO2P2: 322.1126;
found: 322.1130.
Acknowledgment
This project was supported by the Hungarian Scientific and Re-
search Fund (OTKA K83118).
Butylbis(3,4-dimethyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (7a)
Slightly yellowish oil; yield: 0.66 g (94%).
IR (film): 2932, 1611, 1235, 1186, 788 cm–1.
References
3
1H NMR (700 MHz, CDCl3): δ = 0.89 (t, J(HH) = 7.4 Hz, 3 H,
(1) Quin, L. D. The Heterocyclic Chemistry of Phosphorus:
System Based on the Phosphorus–Carbon Bond; Wiley:
New York, 1981, 30.
(2) Quin, L. D. In Comprehensive Heterocyclic Chemistry II;
Vol. 2; Katritzky, A. R.; Rees, C. W.; Scriven, E. F. V., Eds.;
Pergamon/Elsevier: Oxford, 1996, Chap. 2.15, 826.
(3) Phosphorus–Carbon Heterocyclic Chemistry: The Rise of a
New Domain; Mathey, F., Ed.; Pergamon: Amsterdam,
2001, 195.
(4) Quin, L. D. A Guide to Organophosphorus Chemistry;
Wiley & Sons: New York, 2000, 249.
(5) Bodalski, R.; Pietrusiewicz, K. M.; Koszuk, J. Tetrahedron
1975, 31, 1907.
CH3CH2), 1.19–1.34 (m, 2 H, CH2), 1.55–1.66 (m, 2 H, CH2), 1.72
(s, 12 H, 2 C3–CH3, 2 C4–CH3), 2.42–2.82 (m, 8 H, 4 PCH2), 3.00–
3.17 (m, 2 H, NCH2).
13C NMR (176 MHz, CDCl3) {1H}: δ = 13.8 (CH3CH2), 16.7 (m,
C3–CH3), 20.4 (CH3CH2), 34.2 (NCH2CH2), 39.3 (d, 1J = 82.5 Hz)
(C2), 44.4 (NCH2), 128.0 (m, C3).
13C NMR (125.8 MHz, CDCl3) {1H, 31P}: δ = 13.8 (CH3CH2), 16.7
(C3–CH3), 20.4 (CH3CH2), 34.2 (NCH2CH2), 39.3 (C2), 44.4
(NCH2), 128.0 (C3).
31P NMR (283.4 MHz, CDCl3): δ = 59.7.
HRMS (ESI): m/z [M + H]+ calcd for C16H30NO2P2: 330.1752;
(6) Pakulski, Z.; Kwiatosz, R.; Pietrusiewicz, K. M.
Tetrahedron Lett. 2003, 44, 5469.
found: 330.1751.
(7) Pakulski, Z.; Kwiatosz, R.; Pietrusiewicz, K. M.
Tetrahedron 2005, 61, 1481.
(8) Pakulski, Z.; Koprowski, M.; Pietrusiewicz, K. M.
Tetrahedron 2003, 59, 8219.
(9) Pakulski, Z.; Pietrusiewicz, K. M. Tetrahedron: Asymmetry
2004, 15, 41.
(10) Haritha, B.; Reddy, V. K.; Oshikawa, T.; Yamashita, M.
Tetrahedron Lett. 2004, 45, 1923.
(11) Yamada, M.; Yamashita, M.; Suyama, T.; Yamashita, J.;
Asai, K.; Niimi, T.; Ozaki, N.; Fujie, M.; Maddali, K.;
Nakamura, S.; Ohnishi, K. Bioorg. Med. Chem. Lett. 2010,
20, 5943.
(12) Reddy, V. K.; Haritha, B.; Oshikawa, T.; Yamashita, M.
Tetrahedron Lett. 2004, 45, 2851.
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Haritha, B.; Suzuki, K.; Takahashi, M.; Oshikawa, T.
Tetrahedron Lett. 2003, 44, 3455.
Benzylbis(3,4-dimethyl-2,5-dihydro-1H-phosphol-1-yl)amine
P,P′-Dioxide (7e)
Dense, slightly yellowish oil; yield: 0.62 g (90%).
IR (film): 2930, 1605, 1238, 1195, 763 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.68 (s, 12 H, 4 C3–CH3), 2.36–
2.78 (m, 8 H, 4 PCH2), 4.38–4.52 (m, 2 H, NCH2), 7.23–7.38 (m, 5
H, Ar).
3
13C NMR (75.5 MHz, CDCl3): δ = 16.4 (m, J = 16 Hz, C3–CH3),
38.8 (1J = 81.9 Hz) C2, 46.5 (NCH2), 126.5 (C2′′)*, 127.5 (C4′′),
127.8 (m, C3), 128.7 (C3′′)*, 138.2 (C1′′); * interchangeable.
31P NMR (121.5 MHz, CDCl3): δ = 62.2.
HRMS (ESI): m/z [M + H]+ calcd for C19H28NO2P2: 364.1595;
found: 364.1605.
Bis(3-methyl-2,5-dihydro-1H-phosphol-1-yl)amineP,P′-Oxides
6c–e by the Phosphinoylation of 1-Amino-3-methyl-2,5-di-
hydro-1H-phosphole 1-Oxides 5c–e; General Procedure
To 1-hydroxy-3-methyl-2,5-dihydro-1H-phosphole 1-oxide (1,
0.50 g, 3.8 mmol) in anhyd CH2Cl2 (3 mL) was added SOCl2 (0.35
mL, 4.7 mmol) and the mixture was stirred at 26 °C for 24 h. The
solvent was evaporated and the volatile components were removed
under vacuum. The 1-chloro-3-methyl-2,5-dihydro-1H-phosphole
1-oxide (3, 0.57 g, ~100%) so obtained was taken up in anhyd tolu-
ene (3 mL) and Et3N (0.53 mL, 3.79 mmol) was added. Then the
soln of 1-amino-3-methyl-2,5-dihydro-1H-phosphole 1-oxides (5c:
0.82 g, 5d: 0.82 g, 5e: 0.84g; 3.8 mmol) in anhyd toluene (2 mL)
was added. The contents of the flask were stirred at reflux for 4 h.
Then the amine hydrochloride salt was removed by filtration and
the filtrate evaporated. The crude product was purified by column
chromatography (silica gel, 3% MeOH–CHCl3) to afford bis(2,5-di-
hydro-1H-phospholyl)amine derivatives 6c–e.
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Asymmetry 2007, 18, 2965.
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6c
Yield: 0.6 g (58%).
31P NMR (121.5 MHz, CDCl3): δ = 67.38 and 67.40.
6d
Yield: 1.0 g (83%).
31P NMR (121.5 MHz, CDCl3): δ = 66.9.
6e
(27) Pietrusiewicz, K. M.; Flis, A.; Ujj, V.; Körtvélyesi, T.;
Drahos, L.; Pongrácz, P.; Kollár, L.; Keglevich, G. Heteroat.
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Yield: 0.63 g (81%).
31P NMR (121.5 MHz, CDCl3): δ = 69.1.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 199–204

204
N. Z. Kiss et al.
PAPER
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Synthesis 2013, 45, 199–204
© Georg Thieme Verlag Stuttgart · New York