Optimization of Phosphoramidates Synthetic Conditions

Article abstract of DOI:10.1134/S1070363218030271

An optimized catalytic oxidative cost effective process of dehydrogenative coupling of diisopropyl phosphite with arylamines led to formation of the corresponding phosphoramidates. Structures of products were elucidated from NMR and ESI-MS data.

Full text of DOI:10.1134/S1070363218030271

ISSN 1070-3632, Russian Journal of General Chemistry, 2018, Vol. 88, No. 3, pp. 564–565. © Pleiades Publishing, Ltd., 2018.
1
Optimization of Phosphoramidates Synthetic Conditions
N. D. Khan* and H. Khan**
Department of Chemistry, University of Science and Technology Bannu, Khyber Pakhtunkhwa, 28100 Pakistan
e-mail: *ndkhan37@yahoo.com; **hizbmarwat@gmail.com
Received October 29, 2017
Abstract—An optimized catalytic oxidative cost effective process of dehydrogenative coupling of diisopropyl
phosphite with arylamines led to formation of the corresponding phosphoramidates. Structures of products
were elucidated from NMR and ESI-MS data.
Keywords: oxidative cross coupling, diisopropyl phosphite, arylamine, catalysis, conditions optimization
DOI: 10.1134/S1070363218030271
INTRODUCTION
native methods for phosphoramidates synthesis were
of considerable importance. The coupling reaction
leading to the synthesis of phosphoramidates could not
proceed without a catalyst. Dehydrogenative cross
coupling under transition metal catalysis was con-
sidered to be one of most promising approaches to
phosphoramidates.
Preparation of organophosphorus compounds via
transition metal catalysed oxidative dehydrogenative
coupling reaction has recently attracted close attention
[
1, 2]. Phosphoramidates are usually synthesized by
the Atherton–Todd reaction was applied to synthesize
phosphoramidates. However, the most obvious draw-
back of the method is stoichiometric amount of CCl4
involved in it [1]. Therefore, development of alter-
Generally, the method applied in the current study
can be expressed as follows:
H
O
O
O
5
mol % Cu catalyst
R
R
R
NH +
P
P
+
2
N N
O
EtOAc, room temperature,
22 h
O
O
R
NH
Phosphoramidate
Diazo
RESULTS AND DISCUSSION
tested in the range of temperature 0–60°C, in the
atmosphere of N2 and O . According to the
2
Specifically, the current study was devoted to the
reaction of diisopropyl phosphite with aniline and its
substituted derivatives, 4-floroaniline, 4-chloroaniline,
experimental data, CuBr catalyst, ethyl acetate media,
at 20°C in the aerobic environment were determined to
be the most efficient giving high yields of the products
along with small amounts of side products (Tables 1, 2).
2
-bromoaniline, 4-methoxy aniline, and 4-methyl-
aniline. The process led to formation of the cor-
responding products 1–6.
1
Structures of products were elucidated from H and
P NMR, and ESI-MS spectral data.
3
1
The products were insoluble in water and readily
soluble in methanol and acetone.
EXPERIMENTAL
Diisoproyl phosphites, arylamines and catalysts
Optimization of the reaction conditions. In the
model reaction 1 equiv of diisopropyl phosphite was
added over the period of 30 min to p-toluidine
were purchased from Sigma-Aldrich and used without
further purification. All solvents were analytical grade
and used without purification. NMR spectra were
measured on a Bruker AM 400 plus spectrometer in
(
1.5 equiv). In the absence of a catalyst no desired
product was detected beyond the diazo compounds
formed as side products. Various copper catalysts were
CDCl using TMS as the internal standard. Mass
3
spectra were measured on an Agilent 6890-5973N
GCMS-EI spectrometer.
1
The text was submitted by the authors in English.
5
64

OPTIMIZATION OF PHOSPHORAMIDATES SYNTHETIC CONDITIONS
565
Table 1. Optimization of reaction conditions (solvents and
catalysts)
Table 2. Optimization of temperature
Temperature, °C
0
Yield, %
Solvent
Catalyst, 5 mol %
Yield, %
19
7
49
78
73
46
31
17
5
Acetone
Acetone
Acetone
Acetone
EtOAc
CuCl
CuO
CuBr
1
2
3
4
0
0
0
0
11
49
CuBr
CuCl
CuI
2
2
2
32
23
EtOAc
14
50
60
EtOAc
CuBr
CuBr
CuCl
CuI
78
EtOAc
53
7
8
0
0
Toluene
Toluene
Toluene
Toluene
5
0
3
CuBr
CuBr
29
3
1
d.d.d (2H, J = 8.1, 1.4, 0.5 Hz). P NMR spectrum, δ,
17
+
ppm: 0.05. ESI-MS, m/z: 293 [M + H] .
Diisopropyl-N-(2-bromophenyl)phosphoramidate
4). mp 31°C. H NMR spectrum, δ, ppm: 1.33–1.35 d
12H), 1.22 d (J = 6.3 Hz), 4.67–4.76 s (2H, J = 6.3 Hz),
.58–6.63 (2H), 6.99 d.d.d (J = 7.9, 7.7, 1.3 Hz), 7.05
d.d.d (J = 7.8, 1.3, 0.5 Hz)), 7.07–7.09 d.d.d (1H, J =
Coupling of diisopropyl phosphite with aryl-
amines. To a mixture of an arylamine (1.5 mmol) with
CuBr (0.05 mmol, 5 mol %) were added EtOAc
1
(
(
6
(
1 mL) and diisopropyl phosphite (1 mmol) drop wise
in 30 min. The reaction mixture was stirred on a
magnetic stirrer for 22 h at 20°C under the atmosphere
of the air. The following dilution with ethyl acetate
7
0
.8, 7.7, 1.6 Hz), 7.11–7.38 d.d.d (1H, J = 7.9, 1.6,
3
1
.5 Hz). P NMR spectrum, δ, ppm: 0.12. ESI-MS,
+
m/z: 337 [M + H] .
(
20 mL) and washing with brine (30 mL) led to
formation of the organic layer which was separated
and dried over Na SO . The solvent was distilled off
under reduced pressure. The residue was separated by
column chromatography using DCM and n-hexane (1 : 3)
as an eluent. Finally, MeOH was passed through the
column to elute the remaining traces of phosphoramidate.
Diisopropyl-N-(4-methoxyphenyl)phosphoramidate
5). mp 51°C. H NMR spectrum, δ, ppm: 1.20–1.38 d
12H), 1.22 d (J = 6.3 Hz), 2.26 s (3H), 4.62–4.70 sept
2
4
1
(
(
(
2H, J = 6.3 Hz), 6.86 d.d.d (2H, J = 8.1, 1.3, 0.5 Hz),
31
7
.03 d.d.d (2H, J = 8.1, 1.4, 0.5 Hz). P NMR
+
spectrum, δ, ppm: 0.21. ESI-MS, m/z: 287 [M + H] .
Diisopropyl-N-phenylphosphoramidate (1). mp
1
–
1
6
(
0
3°C. H NMR spectrum, δ, ppm: 1.23–1.37 d (12H),
.22 d (J = 6.3 Hz), 4.45–4.63 s (2H, J = 6.3 Hz), 6.39–
.87 d.d.d (3H, J = 8.1, 1.3, 0.5 Hz), 7.03–7.16 d.d.d
Diisopropyl-N-(4-methylphenyl)phosphoramidate
1
(6). mp 39°C. H NMR spectrum, δ, ppm: 1.21–1.38 d
(12H), 1.22 d (J = 6.3 Hz), 2.26 s (3H), 4.63–4.71 s
(2H, J = 6.3 Hz), 6.384–6.86 d.d.d (2H, J = 8.1,
3
1
2H, J = 8.1, 1.4, 0.5 Hz). P NMR spectrum, δ, ppm:
.04. ESI-MS, m/z: 257 [M + H] .
+
31
0.5 Hz), 7.02–7.04 d.d.d (2H, J = 8.1, 1.4, 0.5 Hz). P
NMR spectrum, δ, ppm: 0.17. ESI-MS, m/z: 271
+
Diisopropyl-N-(4-fluorophenyl)phosphoramidate
[
M + H] .
1
(
(
2). mp –2°C. H NMR spectrum, δ, ppm: 1.28–1.38 d
12H), 1.22 d (J = 6.3 Hz), 4.05–4.20 s (2H, J = 6.3 Hz),
REFERENCES
6
.92–6.93 d.d.d (2H, J = 8.1, 1.3, 0.5 Hz), 7.13–7.15
3
1
d.d.d (2H, J = 8.1, 1.4, 0.5 Hz). P NMR spectrum, δ,
ppm: 0.05. ESI-MS, m/z: 275 [M + H] .
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+
Diisopropyl-N-(4-chlorophenyl)phosphoramidate
1
(
3). mp 67°C. H NMR spectrum, δ, ppm: 1.22–1.30 d
(12H), 1.22 d (J = 6.3 Hz), 4.63–4.71 s (2H, J = 6.3 Hz),
6
.88–6.90 d.d.d (2H, J = 8.1, 1.3, 0.5 Hz), 7.17–7.20
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 88 No. 3 2018