The preparation and properties of some α-acyloxy- and α-carbamoyloxy-phosphonothionates

Article abstract of DOI:10.1080/10426500307878

New α-acyloxy and α-carbamoyloxy derivatives of dimethyl 2,2,2-trichloroethyl-phosphonothionate have been prepared, characterized, and screened for activity against free-living soil nematodes. Several of the more easily hydrolysable esters, and also the N-methylcarbamoyl derivative, were as active as the parent pesticide, dimethyl α-hydroxy2,2,2-trichloroethylphosphonothionate, after an induction period during which the active species is assumed to be released in vivo. It is concluded that the 2,2,2-trichloroethyl group is essential for activity in compounds of these types and that the presence of the N-methylcarbamoyl group does not in itself confer activity.

Full text of DOI:10.1080/10426500307878

This article was downloaded by: [Umeå University Library]
On: 17 November 2014, At: 22:47
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954 Registered office: Mortimer House,
37-41 Mortimer Street, London W1T 3JH, UK
Phosphorus, Sulfur, and Silicon and the Related
Elements
Publication details, including instructions for authors and subscription information:
http://www.tandfonline.com/loi/gpss20
The Preparation and Properties of Some α-Acyloxy- and
α-Carbamoyloxy-Phosphonothionates
Harry R. Hudson a , Zsuzsa M. Jászay a & Max Pianka a
a University of North London , London, United Kingdom
Published online: 27 Oct 2010.
To cite this article: Harry R. Hudson , Zsuzsa M. Jászay & Max Pianka (2003) The Preparation and Properties of Some
α-Acyloxy- and α-Carbamoyloxy-Phosphonothionates, Phosphorus, Sulfur, and Silicon and the Related Elements, 178:7,
1571-1582, DOI: 10.1080/10426500307878
To link to this article: http://dx.doi.org/10.1080/10426500307878
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained
in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the
Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and
should be independently verified with primary sources of information. Taylor and Francis shall not be liable for
any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever
or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of
the Content.
This article may be used for research, teaching, and private study purposes. Any substantial or systematic
reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any
form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http://
www.tandfonline.com/page/terms-and-conditions

Phosphorus, Sulfur, and Silicon, 178:1571–1582, 2003
C
Copyright Taylor & Francis Inc.
ISSN: 1042-6507 print
DOI: 10.1080/10426500390212988
THE PREPARATION AND PROPERTIES
OF SOME -ACYLOXY- AND
-CARBAMOYLOXY-PHOSPHONOTHIONATES
Harry R. Hudson, Zsuzsa M. Ja´szay,
and Max Pianka
University of North London, London, United Kingdom
(Received January 28, 2003)
New -acyloxy and -carbamoyloxy derivatives of dimethyl 2,2,2-
trichloroethyl-phosphonothionate have been prepared, characterized,
and screened for activity against free-living soil nematodes. Several of
the more easily hydrolysable esters, and also the N-methylcarbamoyl
derivative, were as active as the parent pesticide, dimethyl -hydroxy-
2,2,2-trichloroethylphosphonothionate, after an induction period dur-
ing which the active species is assumed to be released in vivo. It is con-
cluded that the 2,2,2-trichloroethyl group is essential for activity in com-
pounds of these types and that the presence of the N-methylcarbamoyl
group does not in itself confer activity.
Keywords: Acyloxy; carbamoyloxy; nematicidal activity; phosphonoth-
ionate
Phosphonic acids and their derivatives are of widespread interest as
biologically active molecules in the medical and agrochemical fields.1
One important application in the control of insect pests and parasites
is dependent on anticholinesterase activity for which it is a normal re-
quirement that a suitable leaving group (Y) should be attached to phos-
phorus (1, R1 and/or R2 = alkyl, alkoxy, dialkylamino; X = O or S; Y = F,
CN, p-O2NC6H4O, or other good leaving group).2 In the absence of such
a leaving, group activity may depend upon molecular rearrangement
We are grateful to British Technology Group for financial support and to Mr. Ian Cook
and Dr. Richard A’Court for helpful discussions and advice. We also thank Dr. Anne Terry
and Dr. Paul Matewele for biological screening.
Permanent address: Organic Chemical Technology Research Group of the Hungarian
Academy of Sciences, Budapest University of Technology and Economics, 1521 Budapest,
Hungary.
The late Professor Max Pianka, to whose memory this paper is dedicated.
Address correspondence to Harry R. Hudson, Emeritus Professor of Chemistry, Uni-
versity of North London, 166-220 Holloway Road, London N7 8DB, UK.
1571

1572
H. R. Hudson et al.
for activation or the presence in the molecule of some other source
of activity, e.g., a carbamate moiety.3 An important example involving
rearrangement of the parent molecule is provided by dimethyl 2,2,2-
trichloro-1-hydroxyethylphosphonate (2a) which finds application as a
low toxicity domestic insecticide (trichlorfon),4 and as an anthelmintic
agent (metrifonate) in the control of Schistosoma haematobium.5 The
molecule readily rearranges with the elimination of hydrogen chloride
in alkaline conditions (Scheme 1) to give dimethyl 2,2-dichlorovinyl
phosphate (3),6 otherwise known as the insecticide dichlorvos7 and it
is likely that a similar rearrangement occurs in vivo. The butanoic es-
ter (butonate, 2b)8 has also been reported as a propesticide which may
yield dichlorvos (possibly via the intermediate formation of trichlorfon)
by enzymic degradation.7
SCHEME 1
Other derivatives of trichlorfon claimed as agricultural insecticides9
include the N-substituted carbamates or urethans (2c) which also may
be expected to act as propesticides of dichlorvos, either via hydroysis
to give trichlorfon and subsequent rearrangement (Scheme 1), or by
direct rearrangement with concerted cleavage of the O CO and C Cl
bonds. Although the activity of these carbamates and of other analogous
dialkyl esters (R = Et, etc.)9 might alternatively be associated with the
carbamate moiety, it is normally only N-methyl- or (less frequently)
N,N-dimethyl-carbamates which are insecticidal.3

-Acyloxy- and -Carbamoyloxy-phosphonothionates
1573
The -carbamoyloximinoalkylphosphonates (4) constitute another
class of insecticidal phosphonates10,11 which do not have a conventional
leaving group attached directly to the phosphorus atom and for which
alternative activation sequences can be envisaged. In these cases also
the carbamoyl group (especially the N-methylcarbamoyl group or a suit-
able precursor of this group) might account for their activity as anti-
cholinesterases although the possibility of intramolecular rearrange-
ment to give an active organophosphate species cannot be excluded.
There is no evidence presently available to show whether such an
activation mechanism is involved in vivo but it is worth noting that
-hydroxyiminophosphonates are known to undergo Beckmann rear-
rangement, or to fragment with the elimination of alkyl cyanide ac-
cording to conditions,12 and that either of these processes could lead to
the formation of an active phosphorylating agent.
DISCUSSION
The purpose of this article is to report the preparation and prop-
erties of some new ester and carbamoyl derivatives of the thiono
analogue of trichlorfon, viz. dimethyl 2,2,2-trichloro-1-hydroxye-
thylphosphonothionate (5a).13 Thiono compounds may have practi-
cal advantages as insecticides over the oxygen analogues (to which
they are converted in vivo) because of their generally lower mam-
malian toxicities.2,3 Ester derivatives may provide for the con-
trolled release of the parent molecule in vivo. The only esters of
2,2,2-trichloro-1-hydroxyethylphosphonothionates reported in the lit-
erature are the acetates of diethyl and diisopropyl 2,2,2-trichloro-
1-hydroxyethylphosphonothionate (5b, 5c respectively). These com-
pounds were obtained during a study of the chemistry of O,O-dialkyl

1574
H. R. Hudson et al.
SCHEME 2
S-acetyl phosphorothioites, being formed by the interaction of the
latter with chloral.14 Their biological activity was not, however,
discussed.
In the present work, dimethyl 2,2,2-trichloro-1-hydroxyethylphos-
phonothionate (5a) was prepared as described13 by the base-catalyzed
interaction of dimethyl phosphonothionate (6a) with chloral, and was
then esterified by addition of the appropriate acyl halide (Scheme 2),
to give the acetate, mono-, di-, and trichloro-acetates, the triflu-
oroacetate, and the mixed methyl carbonate (7a–7f respectively).
The N-methylcarbamoyl (8a) and N-phenylcarbamoyl derivatives
(8b) were formed by reaction of the hydroxyphosphonate (5a) with
methyl or phenyl isocyanate in the presence of a catalytic quan-
tity of dibutyltin dilaurate (Scheme 3), as described elsewhere for
the carbamoylation of trichlorfon.15 For purposes of comparison, N-
methylcarbamoyl derivatives also are reported for related phospho-
nothionates in which the trichloromethyl group is replaced by t-butyl
(10a) or phenyl (10b), and for dimethyl -(N-methylcarbamoyloxy)-
2,4,6-trimethylbenzylphosphonate (10c). Products were purified by col-
umn chromatography on Kieselgel 60 and were characterized by a com-
bination of elemental analysis, nmr, and ir spectroscopy.
SCHEME 3

-Acyloxy- and -Carbamoyloxy-phosphonothionates
1575
SCHEME 4
Spectroscopy
1H, 13C, and 31P nmr data for all compounds are shown in the Experi-
mental section. As noted previously for -hydroxyphosphonates,16 the
two alkoxy groups attached to phosphorus are anisochronous and give
rise to separate 1H and 13C signals by virtue of the presence of a chiral
-carbon atom. Thus, the methoxy groups for most compounds appear
as two overlapping doublets (1 H 0.01–0.02 ppm; JPOCH 13.8–14.7 Hz).
The largest chemical shift difference (1 H 0.32 ppm) is exhibited by the
methoxy groups of the -mesityl derivative (10c), while the -phenyl
derivatives (8b, 10b) are exceptional in that no separation of the signals
is observable. Chemical shift differences for the two methoxy groups in
the 13C spectra of all compounds are consistently in the range 1 C 0.3–
0.6 ppm (JPOCH 5.8–6.7 Hz).
The presence of P S in the compounds under investigation is con-
firmed by characteristic 31P nmr signals in the region
80–90 ppm.17
P
Infrared spectroscopy is less useful for the unambiguous identification
of this group for which stretching absorptions are usually relatively
1
weak.18 Absorption frequencies between 584 and 632 cm have been
reported for the P S bond in several phosphonothionates19 and a band
1
at 628 cm has been assigned to P S in diethyl and diisopropyl 1-
acetoxy-2,2,2-trichloroethylphosphonothionate (5b and 5c).14 Our com-
pounds, which are closely related to 5b and 5c, exhibit absorptions of
weak to medium intensity between 600 and 630 cm 1 which may be at-
tributed tentatively to the P S stretching vibration. Strong carbonyl
1
absorptions are exhibited in the range 1770–1805 cm by the car-
1
boxylic esters (7a–7f) and 1715–1758 cm by the carbamates (8a, 8b,
10a). The P O C linkage also gives rise to a characteristically strong
1
absorption for all compounds between 1030 and 1057 cm
.

1576
H. R. Hudson et al.
SCHEME 5
Biological Activity
Screening against free-living soil nematodes showed the pesticide
trichlorfon (2a) and its thiono analogue (5a) to be as active at 50 ppm
as the commercial nematicide, aldicarb (11). Under identical conditions
the acetate (7a) and monochloroacetate (7b) were inactive. However, the
di- and trichloroacetates (7c, 7d), the methoxycarbonyl derivative (7e),
and the N-methylcarbamoyl derivative (8a) showed similar activity to
that of the parent hydroxyphosphonate (5a) after an induction period of
24 h, indicating that the active species was being released gradually in
vivo. The triflouroacetate (7f), which hydrolyzed rapidly in water, imme-
diately showed similar activity to 5a. The total absence of nematicidal
activity in dimethyl 1-hydroxy-2,2,2-trimethylethylphosphonothionate
(9a) and in the N-methylcarbamoyl derivatives 10a, 10b, and 10c, con-
firms the requirement that the 2,2,2-trichloroethyl group should be
present and shows also that the N-methylcarbamoyl group does not
in itself give rise to activity in compounds of these types.† The N-
phenylcarbamate (8b) also was inactive.
EXPERIMENTAL
Starting Materials
General reagents and research chemicals were obtained from
Aldrich Chemical Company. Methyl isocyanate was kindly sup-
plied as a gift by Glaxo Research, Ware, Herts. Dimethyl 2,4,6-
trihydroxybenzylphosphonate (9c)20 was available in the laboratory
and was spectroscopically pure.
Analytical and Instrumental Methods
Microanalysis (for C, H, N, and S) was carried out on a Carlo Erba
1106 Elemental Analyser. 1H, 13C, and 31P NMR spectra were recorded
As a convenient and simple method of preliminary screening for nematicidal activity,
tests were made by visual observation under a microscope of free-living soil nematodes
in an aqueous environment. (Method devised by Dr. Anne Terry of this department.)
†Similar results have been obtained in studies of a series of P O analogues of the type
(MeO)2P(O)CR1R2OCONHMe, none of which showed activity except for the trichlorfon
derivative (R1 = H; R2 = CCl3) (R.O. Yusuf, unpublished).

-Acyloxy- and -Carbamoyloxy-phosphonothionates
1577
for solutions in CDCl3, using a Bruker AM250 FT spectrometer
1
operating at 250.133 or 62.896 MHz for H and 13C spectra respec-
tively. 31P spectra were recorded either on the Bruker AM250 instru-
ment operating at 101.256 MHz, or a Bruker WP80 FT spectrome-
ter operating at 32.292 MHz. Chemical shifts are reported relative to
1
TMS (internal reference) for H and 13C spectra and to 85% H3PO4
(external reference) for 31P spectra. Infrared spectra were obtained
for liquid films on a Bio-Rad FT S40 instrument. Electron impact
mass spectra were run on a Kratos Profile spectrometer operating at
70 eV.
Preparation of Intermediates
Dimethyl Phosphonothionate (6a)
Trimethyl phosphite (93.1 g, 0.75 mmol) was added to an excess of
liquefied hydrogen sulfide (ca. 40 ml) and N,N-diethylaniline (56 g,
0.38 mmol) in a stirred stainless steel autoclave and the mixture was
heated for 24 h at 53–54 C (pressure 12–3 atm.).21 After evaporation
of unreacted hydrogen sulphide and removal of by-product methanol
under reduced pressure, the residue was distilled to give the prod-
uct (46.7 g), b.p. 66 C at 20 mmHg (lit.22 52–53.5 C at 16.5 mmHg),
and a higher fraction (28.4 g), b.p. 66–76 C at 20 mmHg, containing
some diethylaniline. The latter was removed by washing a solution
in dichloromethane with dilute hydrochloric acid, followed by drying
(MgSO4) and redistilling to give a further quantity (17.9 g) of pure prod-
uct (total yield 68.4%) (Found: C, 19.08; H, 5.57. C2H7O2PS requires:
C, 19.04; H, 5.59%);
(d, 1H, P H, JPH651.8 Hz);
(CDCl3) 3.77 (d, 6H, MeO, JPOCH14.3 Hz), 7.72
H
(CDCl3) 52.5 (d, MeO, JPOC6.7 Hz);
C
P
(CDCl3) 75.0 (d sept, JPH 652.3 Hz, JPOCH 14.4 Hz).
Diethyl Phosphonothionate (6b)
Hydrogen sulphide gas was passed into an ice-cold solution23
of diethyl phosphorochloridite (prepared as described)24 (25.8 g,
0.165 mmol) and pyridine (13.2 g, 0.167 mmol) in petroleum (b.p. 60–
80 C) (160 ml). The temperature rose to 25 C. After 10 min the pre-
cipitate of pyridinium chloride was filtered off (17.5 g, 92%) and the
filtrate was concentrated and distilled to give the product (i) (9.6 g,
37.8%), b.p. 73–76 C at 25 mmHg and (ii) (5.1 g, 20.0%, b.p. 76–81 C
at 25 mmHg (lit.25 b.p. 80–81 C at 20 mmHg);
(CDCl3) 1.35 (t, 6H,
H
CH3CH2O, JHCCH 7.1 Hz), 4.0–4.2 (m, 4H, 2 x CH2O), 7.75 (d, 1H, P-
H, JPH647.4 Hz); (CDCl3) 16.2 (d, CH3CH2O, JPOCC 6.7 Hz), 62.3 (d,
C
CH3CH2O, JPOC 6.6 Hz); P (CDCl3) 69.1 (d quintet, JPH 647.8 Hz, JPOCH
10.8 Hz).

1578
H. R. Hudson et al.
1-Hydroxyphosphonates and
1-Hydroxyphosphonothionates
Dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonate (trichlorfon,
2a),6,26
(CDCl3) 17.5, and the corresponding phosphonothion-
C
ate (5a),13
(CDCl3) 92.1, were prepared as described by the
C
condensation of dimethyl phosphonate (6c) or dimethyl phospho-
nothionate (6a), respectively, with chloral. Condensation of dimethyl
phosphonothionate (6a) (0.03 mmol) and 2,2-dimethylpropanal
(0.03 mmol) in the presence of alumina27 gave dimethyl 1-hydroxy-
2,2-dimethylpropylphosphonothionate (9a) as a colourless oily liquid
(66% yield),
(m, 1H, -CH), 3.77 (d, 3H, MeO, JPOCH 13.0 Hz), 3.78 (d, 3H, MeO,
JPOCH13.2 Hz); (CDCl3) 26.8 (d, Me3C, JPCCC 5.8 Hz), 35.3 (d,
C, JPCC 6.0 Hz), 53.5 (d, MeO, JPOC 7.9 Hz), 53.6 (d, MeO, JPOC
(CDCl3) 1.09 (s, 9H, Me3C), 2.86 (br m, OH), 3.58
H
-
C
7.7 Hz), 79.9 (d, -C, JPC 116.1 Hz);
(CDCl3) 101.5; EI-MS m/z
P
(%) 213 (MH+, 43.8), 212 (M+, 43.5). Similarly, diethyl phosphonoth-
ionate (6b) (0.0052 mmol) and benzaldehyde (0.0052 mmol) gave di-
ethyl 1-hydroxybenzylphosphonothionate (9b) (62.8% yield), m.p. 41–
42 C from hexane,
(CDCl3) 1.12 (t, 3H, CH3CH2O, JHCCH 7.1 Hz),
H
1.30 (t, 3H, CH3CH2O, JHCCH 7.1 Hz), 3.17 (br s, 1H, OH), 3.7–3.9 (m,
2H, CH3CH2O), 3.9–4.2 (m, 2H, CH3CH2O), 4.95 (d, 1H, -CH, JPCH
7.1 Hz), 7.26–7.46 (m, 5H, Ar); C (CDCl3) 16.0 (d, CH3CH2O, JPOCC 6.6
Hz), 16.2 (d, CH3CH2O, JPOCC 6.7 Hz), 63.7 (d, CH3CH2O, JPOC 7.7 Hz),
64.3 (d, CH3CH2O, JPOC 7.6 Hz), 74.9 (d, -C, JPC 119.8 Hz), 127–136
(Ar);
(CDCl3) 93.4.
P
General Procedure for the Preparation of O-Acyl
Derivatives of Dimethyl 2,2,2-Trichloro-1-
hydroxyethylphosphonothionate
The acyl chloride (0.008 mmol) was added to a stirred solution of
phosphonothionate (1.36 g, 0.005 mmol) in dichloromethane (20 ml) at
10 to 20 C. Triethylamine (0.8 g, 0.008 mmol) was then added and
stirring was continued at room temperature until the reaction, moni-
tored by TLC, was complete (typically 2–3 h). Pentane was added as
necessary to complete the precipitation of triethylamine hydrochloride
which was filtered off. The oily residue was subjected to column chro-
matography using toluene/petroleum b.p. 60–80 C (95:5) to give the
purified product. The following new compounds were obtained as light
yellow oils:
Dimethyl
(69.8% yield) (Found: C, 23.05; H, 3.21; S, 9.95. C6H10Cl3O4PS re-
quires: C, 22.83; H, 317; S, 10.15%); (CDCl3) 2.28 (s, 3H, MeCO),
1-acetoxy-2,2,2-trichloroethylphosphonothionate
(7a)
H
3.82 (d, 3H, MeO, JPOCH 13.8 Hz), 3.84 (d, 3H, MeO, JPOCH 13.9 Hz),

-Acyloxy- and -Carbamoyloxy-phosphonothionates
1579
5.94 (d, 1H, -CH, JPCH 8.5 Hz);
(CDCl3) 20.6 (MeCO) 54.0 (d, MeO,
C
JPOC 6.7 Hz), 54.5 (d, MeO, JPOC 6.4 Hz), 79.8 (d, -C, JPC 136.4 Hz),
94.6 (d, CCl3, JPCC 7.5 Hz), 168.5 (d, C O, JPCOC 3.7 Hz);
(CDCl3)
P
80.5; IR ( , cm 1) 1771 (s) (C O), 1052 (s), 1029 (s) (P O C), 621(m),
600(w) (P S); EI-MS m/z (%) 314 (M+ for 35Cl3, 18).
Dimethyl
1-chloroacetoxy-2,2,2-trichloroethylphosphonothionate
(7b) (66.7% yield) (Found: C, 20.38; H, 2.65; S, 8.95. C6H9Cl4O4PS re-
quires: C, 20.57; H, 2.57; S, 9.14%); H (CDCl3) 3.83 (d, 3H, MeO, JPOCH
14.0 Hz), 3.85 (d, 3H, MeO, JPOCH 14.1 Hz), 4.29 (s, 2H, CH2Cl), 5.95
(d, 1H, -CH, JPCH 7.9 Hz); C (CDCl3) 40.4 (CH2Cl) 54.0 (d, MeO, JPOC
6.2 Hz), 54.6 (d, MeO, JPOC 6.2 Hz), 80.8 (d, -C, JPC 135.1 Hz), 93.9 (d,
CCl3, JPCC 6.2 Hz), 168.4 (d, C O, JPCOC 3.2 Hz);
(CDCl3) 82.7; IR
P
( , cm 1) 1784 (s) (C O), 1051 (s), 1026 (sh) (P O C), 625 (m) (P S).
Dimethyl 1-dichloroacetoxy-2,2,2-trichloroethylphosphonothionate
(7c) (57.2% yield) (Found: C, 18.98; H, 2.07; S, 8.25. C6H8Cl5O4PS re-
quires: C, 18.73; H, 2.08; S, 8.32%); H (CDCl3) 3.84 (d, 3H, MeO, JPOCH
14.0 Hz), 3.86 (d, 3H, MeO, JPOCH 14.1 Hz), 5.92 (d, 1H, -CH, JPCH
8.2 Hz), 6.15 (s, 1H, CHCl2); C (CDCl3) 54.2 (d, MeO, JPOC 6.0 Hz), 54.6
(d, MeO, JPOC 6.0 Hz), 63.4 (CHCl2), 81.5 (d, -C, JPC 134.5 Hz), 93.6
(d, CCl3, JPCC 6.5 Hz), 162.4 (d, C O, JPCOC 3.6 Hz); P (CDCl3) 81.0; IR
( , cm 1) 1789 (s), 1772 (s) (C O), 1050 (sh), 1036 (s) (P O C), 626 (m),
608 (m) (P S).
Dimethyl 1-trichloroacetoxy-2,2,2-trichloroethylphosphonothionate
(7d) (14.3% yield) H (CDCl3) 3.86 (d, 3H, MeO, JPOCH 14.0 Hz), 3.87 (d,
3H, MeO, JPOCH 14.2 Hz), 5.91 (d, 1H, -CH, JPCH 7.9 Hz);
(CDCl3)
C
54.2 (d, MeO, JPOC 6.3 Hz), 54.6 (d, MeO, JPOC 5.8 Hz), 83.1 (d, -C, JPC
1
134.3 Hz), 93.3 (CHCCl3), 160.0 (C O);
(CDCl3) 80.0; IR ( , cm )
P
1786(s) (C O), 1049(sh), 1035(s) (P O C), 623(w), 607(m) (P S); EI-
MS m/z(%) 409 (0.9), 407 (4.0), 405 (8.4), 403 (10.6), 401 (5.3) ([M-15]+,
Cl isotope cluster).
Dimethyl 1-trifluoroacetoxy-2,2,2-trichloroethylphosphonothionate
(7e) (94.7% yield, not chromatographed) (Found: C, 19.49; H, 2.03; S,
8.85. C6H7Cl3F3O4PS requires: C, 19.49; H, 1.89; S, 8.66%); H (CDCl3)
3.85 (d, 3H, MeO, JPOCH 14.0 Hz), 3.86 (d, 3H, MeO, JPOCH 14.0 Hz), 5.93
(d, 1H, -CH, JPCH 7.8 Hz); (CDCl3) 54.3 (d, MeO, JPOC 6.4 Hz), 54.7
C
(d, MeO, JPOC 6.2 Hz), 82.1 (d, -C, JPC 133.3 Hz), 93.0 (d, CCl3, JPCC
5.5 Hz), 114.3 (quart., CF3, JFC 285.3 Hz), 155.6 (d quart., C O, JFCC
44.7 Hz, JPCOC 3.3 Hz);
(CDCl3) 79.8; IR ( , cm 1) 1805 (s) (C O),
P
1053(sh), 1035(s) (P O C), 629(w), 612(m) (P S).
Dimethyl 1-methoxycarbonyloxy-2,2,2-trichloroethylphosphonothio-
nate (7f) (42.2% yield) (Found: C, 22.08; H, 3.07; S, 9.75. C6H10Cl3O5PS
requires: C, 19.49; H, 1.89; S, 8.66%);
(CDCl3) 3.84 (d, 3H, MeOP,
H
JPOCH 14.7 Hz), 3.85 (d, 3H, MeOP, JPOCH 14.0 Hz), 3.94 (s, 3H, MeOCO),

1580
H. R. Hudson et al.
5.70 (d, 1H, -CH, JPCH 8.2 Hz); C (CDCl3) 54.2 (d, MeOP, JPOC 6.2 Hz),
54.5 (d, MeOP, JPOC 5.8 Hz), 56.3 (MeOCO)83.5 (d, -C, JPC 136.1 Hz),
94.2 (d, CCl3, JPCC 7.7 Hz), 154.3 (d, C O, JPCOC 4.7 Hz);
(CDCl3)
P
82.5; IR ( , cm 1) 1770(s) (C O), 1049(sh), 1030(s) (P O C), 628(m),
611(m) (P S).
Preparation of N-Methyl and N-Phenylcarbamoyl
Derivatives of 1-Hydroxyphosphonates and
1-Hydroxyphosphonothionates
Dimethyl 2,2,2-trichloro-1-(N-methylcarbamoyloxy)ethylphosphon-
othionate (8a) Dimethyl 2,2,2-trichloro-1-hydroxyethylphosphonothi-
onate (5a) (2.73 g, 0.01 mmol) was dissolved in toluene (2 ml). A cat-
alytic amount (one drop) of di-n-butyltin dilaurate was added, followed
by methyl isocyanate (0,63 g, 0.11 mmol), and the mixture was heated
in a sealed ampoule (4 h at 95–100 C). Removal of the toluene un-
der reduced pressure gave an oily residue [ P, 92.7 (starting mate-
rial), 89.7, and 83.7 (desired product)] which was heated again (6 h
at 110 C) with similar quantities of catalyst and methyl isocyanate
to give further reaction). Toluene was removed and the oily residue
(2.65 g) was subjected to column chromatography, using toluene/acetone
(9:1) as eluent, to give a main fraction consisting of dimethyl 2,2,2-
trichloro-1-(N-methylcarbamoyloxy)ethylphosphonothionate (8a) (1.3 g,
39%) as a colorless oil (Found: C, 22.09; H, 3.23; N, 4.37; S, 9.70.
C6H11Cl3NO4PS requires: C, 21.79; H, 3.33; N, 4.24; S, 9.69%);
H
(CDCl3) 2.92 (d, 3H, MeN, JHNCH 4.9 Hz), 3.81 (d, 3H, MeO, JPOCH
13.8 Hz), 3.83 (d, 3H, MeO, JPOCH 13.9 Hz), 5.84 (d, 1H, -CH,
JPCH 9.4 Hz);
C, JPC 138.8 Hz), 95.1 (d, CCl3, JPCC 10.9 Hz), 154.4 (d, C O,
JPCOC 4.2 Hz);
(CDCl3) 83.7; IR ( , cm 1) 1750 (sh), 1735 (s)
(CDCl3) 28.1 (MeN), 54.0 (m, MeO), 80.3 (d,
-
C
P
(C O), 1049 (s), 1027 (s) (P O C), 624 (m), 609 (m) (P S); EI-MS
m/z (%) 335 (9), 333 (24.5), 331 (41.0), 329 (40.8) (M+, Cl isotope
cluster).
General Procedure for the Preparation of
N-Methylcarbamoyl Derivatives of 1-Hydroxy-
phosphonates and Phosphonothionates
The 1-hydroxyphosphonate or phosphonothioate (0.01 mmol), methyl
isocyanate (0.011 mmol), and di-n-butyltin dilaurate (1 drop) were dis-
solved in toluene (4 ml) and heated in a sealed ampoule (8–18 h at
100–110 C), the reaction being monitored by TLC and/or NMR until
complete. After removal of toluene under reduced pressure, the prod-
uct was purified by column chromatography using toluene/aceone (9:1)
as eluent, to give:

-Acyloxy- and -Carbamoyloxy-phosphonothionates
1581
Dimethyl 1-(N-methylcarbamoyloxy)-2,2-dimethylpropylphosphono-
thioate (10a) as a colorless oil (26% yield) (Found: C, 40.33; H, 7.76;
N, 5.15; S, 12.05. C9H20NO4PS requires: C, 40.15; H, 7.43; N, 5.20; S,
11.90%); H (CDCl3) 1.10 (s, 9H, Me3C), 2.85 (d, 3H, MeN, JHNCH 4.9 Hz),
3.73 (d, 6H, MeO, JPOCH 13.4 Hz), 5.06 (d, 1H, -CH, JPCH 8.0 Hz);
C
(CDCl3) 27.0 (d, Me3C, JPCCC 6.0 Hz), 27.8 (MeN), 52.9 (d, MeO, JPOC
6.7 Hz), 53.2 (d, MeO, JPOC 7.0 Hz), 79.5 (d, -C, JPC 129.5 Hz), 156.3
(d, C O, JPCOC 4.5 Hz);
(CDCl3) 93.1; IR ( , cm 1) 1738(sh), 1715(s)
P
(C O), 1057(sh), 1033(s) (P O C), 634(m), 615(m) (P S); EI-MS m/z
(%) 269 (M+, 45.8).
Diethyl -(N-methylcarbamoyloxy)benzylphosphonothioate (10b) as
a white crystalline solid, m.p. 65–68 C (56.7% yield) (Found: C, 49.13;
H, 6.62. C13H20NO4PS requires: C, 49.20; H, 6.35%);
(CDCl3) 1.17
H
(t, 3H, CH3CH2O, JHCCH 7.0 Hz), 1.27 (t, 3H, CH3CH2O, JHCCH 7.0 Hz),
2.79 (d, 3H, MeN, JHNCH 4.9 Hz), 3.8–4.2 (m, 4H, 2 x CH2O), 5.03 (br
s, 1H, NH), 6.11 (d, 1H, -CH, JPCH 11.8 Hz), 7.3–7.5 (m, 5H, Ar);
C
(CDCl3) 16.1 (m, CH3CH2O), 27.7 (MeN), 63.7 (m, CH3CH2O), ca. 80
( -C, overlapping solvent peaks), 128–134 (Ar), 155.5 (d, C O, JPCOC
10.2 Hz);
(CDCl3) 87.4.
P
Dimethyl -(N-methylcarbamoyloxy)-2,4,6-trimethybenzylphosphon-
ate (10c) as a white crystalline solid, m.p. 120–123 C (79.3% yield)
(Found: C, 53.40; H, 7.06; N, 4.36; C14H23NO4P requires: Found: C,
53.33; H, 7.03; N, 4.44%);
(CDCl3) 2.23 (s, 2,6-Me2), 2.58 (s, 4-Me),
H
2.75 (d, 3H, MeN, JHNCH 2.8 Hz), 3.46 (d, 3H, MeO, JPOCH 10.5 Hz),
3.78 (d, 3H, MeO, JPOCH 10.7 Hz), 5.30 (br s, 1H, NH), 6.52 (d, 1H,
-CH, JPCH 18.6 Hz), 6.8 (2H, Ar);
(CDCl3) 20.53 (4-Me), 20.89
C
(2,6-Me2), 27.7 (MeN), 53.3 (d, MeO, JPOC 6.5 Hz), 53.5 (d, MeO, JPOC
7.2 Hz), 68.2 (d, -C, JPC 173.7 Hz), 127–138 (Ar), 155.7 (d, C O, JPCOC
12.2 Hz);
(CDCl3) 22.6.
P
Similarly, the interaction of phenyl isocyanate with dimethyl 2,2,2-
trichloro-1-hydroxyethylphosphonothionate gave:
Dimethyl 2,2,2-trichloro-1-(N-phenylcarbamoyloxy)ethylphosphono-
thionate (8b) (2.4 g, 81.5%), H (CDCl3) 3.82 (d, 6H, MeO, JPOCH 13.8 Hz),
5.93 (d, 1H, -CH, JPCH 9.4 Hz), 7.3–7.5 (5H, Ar);
(CDCl3) 54.0
C
(d, MeO, JPOC 6.7 Hz), 54.3 (d, MeO, JPOC 6.4 Hz), 80.1 (d, -C, JPC
137.3 Hz), 94.8 (d, CCl3, JPCC 10.4 Hz), 154.4 (d, C O, JPCOC 4.2 Hz),
129–136 (Ar), 150.6 (C O);
(CDCl3) 83.7; IR ( , cm 1) 1758(s),
P
1741(sh) (C O), 1054(s), 1030(s) (P O C), 620(m) (P S).
REFERENCES
[1] A. Kalir and H. H. Kalir, Biological Activity of Phosphonic and Phosphinic Acids,
Chapter 9 in Volume 4 of The Chemistry of Organophosphorus Compounds,

1582
H. R. Hudson et al.
edited by F. R. Hartley (John Wiley and Sons Ltd., Chichester, 1996), pp. 767–
780.
[2] M. Eto, Organophosphorus Pesticides: Organic and Biological Chemisty (CRC Press,
Cleveland, Ohio, 1974).
[3] R. J. Cremlyn, Agrochemicals—Preparation and Mode of Action (John Wiley and
Sons Ltd., Chichester, 1991), p. 140.
[4] The Pesticide Manual—a World Compendium, edited by C. D. S. Tomlin (British
Crop Protection Council, Farnham, Surrey, 1997), 11th edition.
[5] Martindale, The Complete Drug Reference, edited by Sean C. Sweetman (Pharma-
ceutical Press, London, 2002), 33rd edition, p. 103–102.
[6] W. Lorenz, A. Henglein, and G. Schrader, J. Am. Chem. Soc., 77, 2554 (1955).
[7] R. J. Cremlyn, Agrochemicals—Preparation and Mode of Action (John Wiley and
Sons Ltd., Chichester, 1991), pp. 112–113.
[8] B. W. Arthur and J. E. Casida, J. Agric. Fd. Chem., 6, 360 (1958).
[9] G. Schrader (to Farbenfabriken Bayer AG), Belg. 632, 366 (1963); Chem. Abstr., 61,
3149a (1964).
[10] W. M. Dixon and M. Kirkwood (to Monsanto Company), U. S. Pat. 3,819,751 (1974).
[11] A. Hartmann, I. Hamman, and B. Homeyer (to Bayer AG), Ger. Offen. 25 53 442
(1977).
[12] E. Breuer, A. Schlossman, M. Safadi, D. Gibson, M. Chorev, and H. Leader, J. Chem.
Soc. Perkin Trans. 1, 3263 (1990).
[13] R. Coelln, W. Sirrenberg, W. Behrenz, and W. Stendel (to Bayer AG), Ger. Offen.
2,512,375 (1975); Chem. Abstr., 86, 90018 (1977).
[14] V. A. Al’fonsov, D. A. Pudovik, E. S. Batyeva, and A. N. Pudovik, Zh. Obshch. Khim.,
58, 1740 (1988).
[15] G. K. Kohn (to California Research Corp.), U.S. Pat. 3,069,312 (1962); Chem. Abstr.,
59, 665a (1963).
[16] H. R. Hudson, M. McPartlin, R. W. Matthews, H. Powell, R. O. Yusuf, Z. M. Ja´szay,
G. Keglevich, I. Petneha´zy, and L. To¨ke, Phosphorus, Sulfur, and Silicon, 79, 239
(1993).
[17] Handbook of Phosphorus-31Nuclear Magnetic Resonance Data, edited by J. C.
Tebby, (CRC Press, Inc., Boca Raton, Fl., 1991), pp. 18, 329.
[18] L. J. Bellamy, The Infrared Spectra of Complex Molecules (Methuen, London, 1958)
2nd edition, p. 321.
[19] R. R. Shagidullin, F. S. Mukhametov, R. B. Nigmatullina, V. S. Vinogradova, and
A. V. Chernova, Atlas IK-Spektrov Fosfororganicheskikh Soedinenii, edited by A. N.
Pudovik (Nauka, Moscow, 1977), p. 15.
[20] R. O. Yusuf, Ph.D. thesis (CNAA), The Polytechnic of North London (1991).
[21] R. Schliebs, Z. Naturforsch. B, 25, 111–112 (1970).
[22] M. I. Kabachnik and T. A. Mastryukova, Izv. Akad. Nauk SSSR, Ser. Khim., 727
(1952); Chem. Abstr., 47, 9909a (1953).
[23] Z. Pelchowicz, J. Chem. Soc., 241 (1961).
[24] H. G. Cook, J. D. Ilett, B. C. Saunders, G. J. Stracey, H. G. Watson, I. G. E. Wilding,
and S. J. Woodcock, J. Chem. Soc., 2921 (1949).
[25] J. Michalski and T. Modro, Rocz. Chem., 38, 123 (1964).
[26] W. F. Barthel, P. A. Giang, and S. A. Hall, J. Am. Chem. Soc., 76, 4186 (1954).
[27] F. Texier-Boulett and A. Foucaud, Synthesis, 165 (1982).