Synthesis and characterization of O,O-dimethyl-N-(2,2,2-trichloro-1- arylaminoethyl) phosphoramidothioates

Article abstract of DOI:10.1080/10426500802453807

Several novel trichloromethyl-containing O,O-dimethyl phosphoramidothioate derivatives have been synthesized by the reaction of O,O-dimethyl phosphoramidothioate with chloral imines. The latter were prepared in good yields by refluxing the dichloroethane

Full text of DOI:10.1080/10426500802453807

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Synthesis and Characterization
of O,O-Dimethyl-N-(2,2,2-
trichloro-1-arylaminoethyl)
Phosphoramidothioates
Baolei Wang a , Xinghai Liu a & Zhengming Li a
a Elemento-Organic Chemistry Institute, State-Key
Laboratory of Elemento-Organic Chemistry , Nankai
University , Tianjin, China
Published online: 04 Sep 2009.
To cite this article: Baolei Wang , Xinghai Liu & Zhengming Li (2009) Synthesis
and Characterization of O,O-Dimethyl-N-(2,2,2-trichloro-1-arylaminoethyl)
Phosphoramidothioates, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:9, 2281-2287
To link to this article: http://dx.doi.org/10.1080/10426500802453807
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Phosphorus, Sulfur, and Silicon, 184:2281–2287, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500802453807
Synthesis and Characterization of
O,O-Dimethyl-N-(2,2,2-trichloro-1-arylaminoethyl)
Phosphoramidothioates
Baolei Wang, Xinghai Liu, and Zhengming Li
Elemento-Organic Chemistry Institute, State-Key Laboratory of
Elemento-Organic Chemistry, Nankai University, Tianjin, China
Several novel trichloromethyl-containing O,O-dimethyl phosphoramidothioate
derivatives have been synthesized by the reaction of O,O-dimethyl phosphorami-
dothioate with chloral imines. The latter were prepared in good yields by refluxing
˚
the dichloroethane solution of chloral and substituted anilines using 3 A molecular
sieves as dehydrating agent. Structures of title compounds were confirmed by IR,
1
31
H NMR, P NMR, and FT-MS studies.
Keywords Phosphoramidothioate; synthesis; trichloromethyl
INTRODUCTION
Organophosphorus compounds, being ubiquitous in nature, have found
many applications. Phosphoramidothioates, bioisosteres of natural
amino acids—α-aminophosphorothioates,1 have been found to exhibit a
wide range of biological activities, such as herbicides, insecticides, and
fungicides.2–5 As a consequence, the interest of organic chemists in the
synthesis of new phosphoramidothioate derivatives remains high. Also
various trichloromethyl-containing compounds are associated with
fungicidal, insecticidal, and plant growth regulatory activities.6–8
There are many reports on the synthesis and biological activities
of organophosphorus compounds during the last 20 years,9,10 but very
Received 9 July 2008; accepted 5 September 2008.
This work was kindly supported by Specialized Research Fund for the Doctoral
Program of Higher Education (No. 20070055044), Tianjin Natural Science Foundation
(No.08JCYBJC00800), and National Natural Science Foundation Project of China (No.
20432010 and 20872069).
Address correspondence to Baolei Wang and Zhengming Li, Elemento-Organic Chem-
istry Institute, Nankai University, Tianjin 300071, China. E-mail: wangbaolei@126.com;
nkzml@vip.163.com
2281

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B. Wang et al.
few reports about the synthesis of phosphoramidothioates. In contin-
uation of our efforts towards the synthesis of various biologically im-
portant compounds, we were interested in the preparation of phos-
phoramidothioates with a trichloromethyl substituent, as it can serve
as a masked carboxylic acid equivalent,11 it can be replaced by other
groups,12,13 and it can also be transformed into a chlorovinyl group.14
To our surprise, there was no general method available for the syn-
thesis of such phosphoramidothioates bearing a trichloromethyl group
at the α-C position, though Drach et al.15 reported the addition of N-
dialkoxyphosphonyltrichloroethylidenimines and amines in 1969. We
herein report a simple and efficient preparation of various chloral
imines and their application in the synthesis novel trichloromethyl-
containing O,O-dimethyl phosphoramidothioate derivatives. The syn-
thetic route of compounds is shown in Scheme 1.
SCHEME 1
RESULTS AND DISCUSSION
Synthesis
We utilized a molecular-sieves–catalyzed method reported by Michiko
et al.16 and Garcia et al.17 for the condensation of arylamine and ketone,
and thus chloral imines were prepared successfully. Initially, a solution
of anhydrous chloral in dichloroethane was treated with aniline at 0–
5◦C and then stirred at room temperature for 10 h or refluxed for 4 h.
The TLC analysis indicated plenty of undehydrated aminol 1 and a
small amount of imine 2 produced, which was further confirmed by
GC-MS. However, we were able to prepare the required chloral imines
2 by continuing to reflux the reaction mixture in the presence of 3 Å
molecular sieves as a dehydrating agent with the removal of the water

Synthesis of Phosphoramidothioates
2283
formed in the reaction. Moreover, the chloral imine 2 was also prepared
directly by refluxing a mixture of anhydrous chloral and aniline in
dichloroethane with the removal of water using 3 Å molecular sieves.
Chloral imines 2a–2g were prepared by this method in good yields.
Most of these imines were highly moisture sensitive and reverted to
the aminols. Imines 2a–2g were further reacted with O,O-dimethyl
phosphoramidothioate via nucleophilic addition in dry benzene under
refluxing conditions to give the phosphoramidothioate derivatives 3a–
3g.
There are methods available for the construction of the various sub-
stituted phosphoramidothioates. However, a widely used method is via
a nucleophilic substitution reaction between phosphonothionic chloride
and amine.18,19 Moreover, there are numerous reports on the phos-
phonylation of Schiff’s base with dialkyl phosphate, which provides
a useful method for access to various substituted phosphoramidates,
in particular, α -aminophosphonate.20,21 In our experiments, referring
to this method, the nucleophilic addition for preparation of the title
phosphoramidothioates occurred smoothly. It can be inferred that a
trichloromethyl group of the imines will increase the susceptibility of
the CH=N group of the Schiff’s base chloral imine towards nucleophilic
attack and make the reaction take place more easily. The mechanism
of the reaction is suggested to be as is shown Scheme 2, according to
the literature.15,22
SCHEME 2
Infrared Spectra
The infrared spectrum of phosphoramidothioate derivatives 3 showed
absorption bands at 3419–3296 cm−1 for N-H stretching. The character-
istic stretching vibrations ν (P-N-C) and ν (P S) appears at 1031–1025
cm−1, 827–787 cm−1, and 753–681 cm−1, respectively.
1H NMR Spectra
In the 1H NMR spectra of 3, the -NH proton signals were observed at δ
3.79–3.84 ppm as a multiplet (S P-NH-CH) and δ 4.16–4.36 ppm as a

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B. Wang et al.
doublet (CH-NH-Ar), respectively. The CH proton appeared at δ 5.47–
5.61 ppm as a quartet due to the influences of both NH protons and “P”
splitting, which indicated the conversion of -CH N- group (CH proton
signal of intermediates 2 was observed at δ 7.86–7.96 ppm as a singlet)
to >CH-NH- group. The methoxyl protons [(CH3O)2P S] appeared at
δ 3.60–3.66 ppm as two doublets due to “P” splitting. The other peaks
observed were the aromatic protons at δ 6.74–7.31 ppm and an addi-
tional singlet at δ 2.26 ppm and δ 2.21 ppm in compounds 3g and 3f,
respectively, due to -CH3 group attached to phenyl ring.
31P NMR Spectra
All the synthesized phosphoramidothioate compounds 3a–3g were
characterized by the downfield 31P NMR signal at δ 74.34–76.83 ppm
due to the induction effect of the trichloromethyl group.23
EXPERIMENTAL
Melting points were determined using a Taike X-4 apparatus and were
uncorrected. Refractive indexes were determined using a WZS-1 Abbe
refractometer. Infrared spectra were recorded on a Nicolet 570 spec-
trophotometer as KBr discs. 1H NMR spectra were measured on a
Bruker AV-300 instrument (300 MHz) using TMS as an internal stan-
dard and CDCl3 as solvent. 31P NMR spectra were measured on a
Varian Mercury Plus 400 instrument (400 MHz) using TMS as an in-
ternal standard and CDCl3 as solvent. HRMS data was obtained on a
FTICR-MS instrument (Ionspec 7.0T).
Synthesis of Substituted-N-(2,2,2-trichloroethylidene) Aniline
(2)
To a stirred solution of chloral (30 mmol) in anhydrous ethylene dichlo-
ride (1 5 mL), substituted aniline (30 mmol) in dry EDC (5 mL) was
added slowly at 0–5◦C, and the reaction mixture was then allowed to
warm to room temperature and stirred for 30 min. It was then refluxed
for 5–8 h with the removal of water using molecular sieves (3 Å). The
reaction mixture was then cooled and concentrated under vacuum to
give the crude product, which was purified by column chromatography
using petroleum ether and ethyl acetate as solvents (volume ratio 30:1)
to yield the chloral imine 2.
2a: Pale yellow oil, yield 73%, n2D8 1.5596; 1H NMR (CDCl3, 400 MHz):
7.93(s, 1H, CH), 7.21–7.45(m, 5H, Ph-H).

Synthesis of Phosphoramidothioates
2285
2b: Yellow oil, yield 96%, n2D8 1.5537; H NMR (CDCl3, 400 MHz):
1
7.93 (s, 1H, CH), 7.10–7.26 (m, 4H, Ph-H).
2c: Yellow oil, yield 75%, n28 1.5879; H NMR (CDCl3, 400 MHz):
1
7.92 (s, 1H, CH), 7.39 (d, J = D8.4 Hz, 2H, Ph-H), 7.18 (d, J = 8.4 Hz,
2H, Ph-H).
2d: Yellow oil, yield 84%, n2D8 1.5805; H NMR (CDCl3, 400 MHz):
1
7.92 (s, 1H, CH), 7.10–7.38 (m, 4H, Ph-H).
2e: Colorless crystals, yield 83%, mp 84–86◦C; 1H NMR (CDCl3, 400
MHz): 7.94 (s, 1H, CH), 7.23 (d, J = 8.0 Hz, 2H, Ph-H), 7.16 (d, J = 8.0
Hz, 2H, Ph-H), 2.39 (s, 3H, CH3).
2f: Yellow oil, yield 88%, n2D8 1.5645; H NMR (CDCl3, 400 MHz):
1
7.86 (s, 1H, CH), 6.94–7.26 (m, 4H, Ph-H), 2.35(s, 1H, CH3).
2g: Yellow oil, yield 95%, n2D8 1.6083; H NMR (CDCl3, 400 MHz):
1
7.96 (s, 1H, CH), 7.03–7.39 (m, 9H, Ph-H).
Synthesis of O,O-Dimethyl-N-(2,2,2-trichloro-1-
arylaminoethyl) Phosphoramidothioates (3)
To a stirred solution of chloral imine (2, 2 mmol) in dry benzene, a
solution of O,O-dimethyl phosphoramidothioate (93% purity, 1.5 mmol)
in dry benzene was added dropwise. The reaction mixture was then
refluxed under nitrogen atmosphere for 16–20 h. Then it was cooled
and concentrated to give a red sticky oil, which was purified by column
chromatography using petroleum ether and ethyl acetate as solvents
(volume ratio 20:1) to yield the title compound 3.
O,O-Dimethyl-N-(2,2,2-trichloro-1-phenylaminoethyl)
Phosphoramidothioate (3a)
Red oil, yield 46%, n2D8 1.6108; IR: 3367(NH), 1603, 1510, 1499, 1456
(benzene ring), 1028 (P-N-C), 827, 751 (P S); 1H NMR (300 MHz):
6.82–7.24 (m, 5H, Ph-H), 5.57 (q, J = 9.9 Hz, 1H, CH), 4.27 (d, J =
10.2 Hz, 1H, Ph-NH), 3.81 (m, 1H, NHP=S), 3.64 (d, JP−H = 13.8 Hz,
3H, OCH3), 3.60 (d, JP−H = 13.8 Hz, 3H, OCH3); 31P NMR (400 MHz):
74.45(P S); ESI-FTMS for C10H14Cl3N2O2PS [M-H]−: Calcd. 360.9506,
Found 360.9502.
O,O-Dimethyl-N-[2,2,2-trichloro-1-(4-flurophenylamino)ethyl]
Phosphoramidothioate (3b)
Red oil, yield 39%, n2D8 1.6160; IR: 3355, 3330(NH), 1611, 1511, 1456
(benzene ring), 1025 (P-N-C), 820, 752 (P S); 1H NMR (400 MHz): 6.85–
6.97 (m, 4H, Ph-H), 5.47 (q, J = 9.6Hz, 1H, CH), 4.18 (d, J = 9.6 Hz, 1H,
Ph-NH), 3.80 (m, 1H, NHP=S), 3.65 (d, JP−H = 14.0 Hz, 3H, OCH3),

2286
B. Wang et al.
3.60 (d, JP−H = 14.0 Hz, 3H, OCH3); 31P NMR (400 MHz): 74.55 (P S);
ESI-FTMS for C10H13Cl3FN2O2PS [M-H]− : Calcd. 378.9412, Found
378.9410.
O,O-Dimethyl-N-[2,2,2-trichloro-1-(4-chlorophenylamino)ethyl]
Phosphoramidothioate (3c)
Red oil, yield 58%, n2D8 1.6522; IR: 3361(NH), 1599, 1504, 1456 (ben-
1
zene ring), 1029 (P-N-C), 819, 683 (P S); H NMR(300 MHz): 7.20 (d,
J = 8.7 Hz, 2H, Ph-H), 6.83 (d, J = 8.7 Hz, 2H, Ph-H), 5.52 (q, J = 9.9
Hz, 1H, CH), 4.29 (d, J = 9.6 Hz, 1H, Ph-NH), 3.82 (m, 1H, NHP=S),
3.66(d, JP−H = 14.1 Hz, 3H, OCH3), 3.62(d, JP−H = 14.1 Hz, 3H, OCH3);
31P NMR (400 MHz): 74.50 (P S); ESI-FTMS for C10H13Cl4N2O2PS
[M-H]− : Calcd. 394.9117, Found 394.9123.
O,O-Dimethyl-N-[2,2,2-trichloro-1-(3-chlorophenylamino)ethyl]
Phosphoramidothioate (3d)
Red oil, yield 54%, n2D8 1.6461; IR: 3360(NH), 1599, 1510, 1483 (ben-
zene ring), 1029 (P-N-C), 825, 681 (P S); 1H NMR (300 MHz): 6.74–7.18
(m, 4H, Ph-H), 5.53 (q, J = 9.9 Hz, 1H, CH), 4.36 (d, J = 9.9 Hz, 1H, Ph-
NH), 3.82 (m, 1H, NHP=S), 3.66 (d, JP−H = 14.1 Hz, 3H, OCH3), 3.64
(d, JP−H = 14.1 Hz, 3H, OCH3); 31P NMR (400 MHz): 74.34(P S); ESI-
FTMS for C10H13Cl4N2O2PS [M-H]−: Calcd. 394.9117, Found 394.9109.
O,O-Dimethyl-N-[2,2,2-trichloro-1-(4-methylphenylamino)
ethyl] Phosphoramidothioate (3e)
Yellow solid, yield 49%, mp 70–72◦C; IR: 3359, 3319(NH), 1617, 1591,
1521, 1495 (benzene ring), 1026 (P-N-C), 797, 744 (P S); 1H NMR (300
MHz): 7.04 (d, J = 8.4 Hz, 2H, Ph-H), 6.79 (d, J = 8.4 Hz, 2H, Ph-H),
5.52 (m, 1H, CH), 4.16 (br, 1H, Ph-NH), 3.79 (m, 1H, NHP=S), 3.64
(d, JP−H = 13.8 Hz, 3H, OCH3), 3.61 (d, JP−H = 13.8 Hz, 3H, OCH3),
2.26 (s, 3H, CH3); 31P NMR (400 MHz): 74.50 (P S); ESI-FTMS for
C11H16Cl3N2O2PS [M-H]− : Calcd. 374.9663, Found 374.9667.
O,O-Dimethyl-N-[2,2,2-trichloro-1-(2-methylphenylamino)
ethyl] Phosphoramidothioate (3f)
Red oil, yield 46%, n2D8 1.6251; IR: 3419, 3296(NH), 1607, 1588, 1548,
1
1456 (benzene ring), 1029 (P-N-C), 787 (P S); H NMR (400 MHz):
6.77–7.20 (m, 4H, Ph-H), 5.61 (q, J = 9.6 Hz, 1H, CH), 4.29 (d, J =
9.6 Hz, 1H, Ph-NH), 3.84 (m, 1H, NHP=S), 3.65 (d, JP−H = 14.0 Hz,
3H, OCH3), 3.63 (d, JP−H = 14.0 Hz, 3H, OCH3), 2.21 (s, 3H, CH3);
31P NMR (400 MHz): 76.83 (P S); ESI-FTMS for C11H16Cl3N2O2PS
[M-H]− : Calcd. 374.9663, Found 374.9666.

Synthesis of Phosphoramidothioates
2287
O,O-Dimethyl-N-[2,2,2-trichloro-1-(4-phenoxyphenylamino)
ethyl] Phosphoramidothioate (3g)
Red oil, yield 41%, n2D8 1.6514; IR: 3334(NH), 1598, 1508, 1488, 1456
(benzene ring), 1031 (P-N-C), 827, 753 (P S); 1H NMR (400 MHz): 6.88–
7.31 (m, 9H, Ph-H), 5.51 (q, J = 9.2 Hz, 1H, CH), 4.21 (d, J = 7.6Hz, 1H,
Ph-NH), 3.81 (m, 1H, NHP=S), 3.66 (d, JP−H = 14.8 Hz, 3H, OCH3), 3.62
(d, JP−H = 14.8 Hz, 3H, OCH3); 31P NMR (400 MHz): 74.50 (P S); ESI-
FTMS for C16H18Cl3N2O3PS [M-H]−: Calcd. 452.9769, Found 452.9764.
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