G. Becker, F.R. Wurm / Tetrahedron 73 (2017) 3536e3540
3537
spectrometer operating with 300 MHz, 75 MHz and 121 MHz or a
Bruker AVANCE III 700 spectrometer operating with 700 MHz,
1
76 MHz and 283 MHz. All spectra were measured either in DMSO-
1
13
d
6
or CDCl
3
. H and C spectra were calibrated against the solvent
3
1
signal, P spectra used as conducted. Spectra were analyzed using
MestReNova 8 from Mestrelab Research S.L. for 1D spectra All
and P NMR spectra are H-decoupled.
13
C
31
1
2
2
.3. Synthesis
.3.1. 2-Chloro-1,3,2-dioxaphospholane (CP, 1a)
A flame-dried 500 mL three-neck flask, equipped with a drop-
ping funnel and a reflux condenser, was charged with phosphorus
trichloride (137.3 g, 1.000 mol) in dry dichloromethane (150.0 mL).
Ethylene glycol (62.07 g, 1.000 mol) was added drop-wise to the
stirred solution, while argon was bubbled through the solution to
remove the released hydrogen chloride. The Ar-stream with
released hydrogen chloride was passed through a NaOH-solution
for neutralization. The reaction was continued for additional 2 h.
Scheme 1. Application examples for 2-chloro-2-oxo-1,3,2-dioxaphospholane (COP) as
precursor.
Then, the solvent was removed and the residue purified by distil-
ꢀ
lation at reduced pressure to give
a
fraction at 72e78 C/
6
0
5e67 mbar, obtaining the clear, colorless, liquid product (84.15 g,
31
.670 mol, yield: 67%). NMR data matches literature values.
1
H NMR (700 MHz, CDCl
3
):
d
4.35e4.13 (m, 4H, O-CH
2
-CH
2
-O).
):
13
31
C NMR (176 MHz, CDCl
167.80.
3
):
d
65.29. P{H}-NMR (283 MHz, CDCl
3
d
Scheme 2. Typical reaction protocol for the preparation of COP.
2.3.2. 2-Chloro-2-oxo-1,3,2-dioxaphospholane (COP, 1)
routes, reported literature protocols include the use of dinitrogen
A flame-dried 500 mL three-neck flask, equipped with a reflux
28
29
tetroxide (N
2
O
4
)
or ozone (O
3
)
as oxidants, also resulting in
condenser, was charged with 2-chloro-1,3,2-dioxaphospholane
(20.00 g, 0.160 mol) dissolved in benzene (250.0 mL) and dry
poor yields in the case of N
2 4
O and challenging handling of reac-
ꢁ
4
tant. Also phosphorus oxychloride, ethylene glycol and catalytic
amounts of copper(I)chloride (CuCl) were reported to produce COP
in a one-step reaction, but several attempts of this protocol in our
CoCl (20.50 mg, 1.590*10 mol) was added. A stream of dried air
2
(passed through conc. H SO ) was passed through the solution for
2
4
ꢀ
3 h at 80 C and for 12h at room temperature (overnight). Subse-
quently, the solvent was removed in vacuo and the residue purified
by fractionated distillation at reduced pressure to give a fraction at
3
0
group did not produce COP in reasonable yields or purity.
There is a high demand in COP. Although commercially avail-
able, price, delivery time and purity of the commercial product are
often unsatisfactory. Therefore an efficient, inexpensive and safer
in-house preparation is indispensable. Herein, we present a facili-
tated synthesis protocol using the oxygen from air as oxidant,
instead of molecular oxygen from a gas bottle. Still used in excess,
large amounts of wasted unreacted molecular oxygen can be
avoided. Additionally, cobalt(II)chloride has been found to be an
efficient catalyst that accelerates the reaction from days to several
hours, resulting in COP with a very high purity and overall
acceptable yields of 70%.
ꢀ
66e74 C/0.13e0.15 mbar, obtaining the clear, colorless, liquid
product COP in high purity (15.82 g, 0.110 mol, yield: 70%, 99%
2
6 1
purity). NMR data matches literature values.
H NMR (300 MHz,
1
3
CDCl ):
3
d
d
4.61e4.44 (m, 4H, O-CH -CH -O), C{H}-NMR (176 MHz,
2
2
31
CDCl ):
3
3
66.54, P{H}-NMR (121 MHz, CDCl ): d 22.74.
2.3.3. Isolation of byproduct in entry 3
After fractionated distillation, 1.500 g of product with non-
phosphorus containing byproduct was stirred in 10 mL DCM with
5.000 g silica gel for 10 min. The silica gel was removed by filtration
and the solvent removed, obtaining the byproducts 1-(benzyl)-4-
methylbenzene and 1-(benzyl)-2-methylbenzene (180.0 mg,
2
. Experimental section
ꢁ
4
6
.420*10 mol, yield: 12%).
2
.1. Materials
Ratio 1-(benzyl)-4-methylbenzene: 1-(benzyl)-2-methylbenzene
1
from H NMR is 0.42: 0.57.
NMR data matches literature values32,33
methylbenzene: H NMR: d 7.29e7.09, 3.93, 2.30. C NMR: d
:
1-(benzyl)-4-
141.5,
138.2, 135.6, 130.4, 129.3, 129.0, 128.6, 126.0, 41.7, 21.1. 1-(benzyl)-2-
All reagents were used without further purification, unless
1
13
otherwise stated. Solvents, dry solvents (over molecular sieves) and
deuterated solvents were purchased from Acros Organics, Sigma-
Aldrich, Deutero GmbH (Germany) or Fluka. Ethylene glycol was
purchased from Sigma-Aldrich, dried prior to use with NaH,
1
13
methylbenzene: H NMR:
d 7.35e7.11, 4.03, 2.23. C NMR: d 140.8,
139.4, 137.1, 130.7, 130.4, 129.2, 128.8, 126.9, 126.4, 126.3, 39.9, 20.1.
3
distilled and stored over molecular sieves. PCl was purchased from
Acros Organics. Cobalt(II)chloride hexahydrate was purchased from
Sigma Aldrich, and dried at reduced pressure at ~500 C directly
prior to use.
2.3.4. 1-(benzyl)-2-methylbenzene
ꢀ
1
2 2
H NMR (300 MHz, CD Cl ): d 7.32e7.11 (m, 8H, aromatic pro-
13
tons), 3.94 (s, 2H, Ar-CH -Ar-CH ), 2.32 (s, 3H, Ar-CH -Ar-CH ).
2
3
2
3
C
{
H}-NMR (75 MHz, CD
2
2
Cl ): d 141.19, 138.86, 136.18, 130.79, 130.41,
2.2. Methods
129.33, 128.96, 126.95, 126.50, 126.44, 39.89, 19.98.
For nuclear magnetic resonance (NMR) analysis H, 13C and 31
1
P
2.3.5. 1-(benzyl)-4-methylbenzene
1
NMR spectra were recorded either on a Bruker AVANCE III 300
2 2
H NMR (300 MHz, CD Cl ): d 7.32e7.11 (m, 8H, aromatic