Surface-mediated synthesis of O-alkyl 2-methoxyethyl alkylphosphonates under solvent free conditions: Potential marker of nerve agents

Article abstract of DOI:10.1080/10426500903496705

This article describes rapid and efficient surface mediated synthesis of O-alkyl 2-methoxyethyl alkylphosphonates from alkylphosphonic acids and alcohols using dicyclohexyl carbodiimide (DCC)-Celite as a solid support. These compounds are markers of nerve agents. 2-Methoxyethyl methylphosphonic acids (2a-d) were reacted with various alcohols to yield O-alkyl 2-methoxyethyl alkylphosphonates (AMEAPs, 3a-m). This synthetic method has advantages over other methods in terms of selectivity, shorter reaction time, high yield, and easy work-up. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500903496705

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Phosphorus, Sulfur, and Silicon and the
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Surface-Mediated Synthesis of O-Alkyl
2-Methoxyethyl Alkylphosphonates
Under Solvent Free Conditions: Potential
Marker of Nerve Agents
Rajesh Kumar a , A. K. Gupta a & M. P. Kaushik a
a Process Technology Development Division , Defence R & D
Establishment , Gwalior, India
Published online: 24 Sep 2010.
To cite this article: Rajesh Kumar , A. K. Gupta & M. P. Kaushik (2010) Surface-Mediated Synthesis
of O-Alkyl 2-Methoxyethyl Alkylphosphonates Under Solvent Free Conditions: Potential Marker of
Nerve Agents, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:10, 2064-2075, DOI:
10.1080/10426500903496705
To link to this article: http://dx.doi.org/10.1080/10426500903496705
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Phosphorus, Sulfur, and Silicon, 185:2064–2075, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903496705
SURFACE-MEDIATED SYNTHESIS OF O-ALKYL
2-METHOXYETHYL ALKYLPHOSPHONATES UNDER
SOLVENT FREE CONDITIONS: POTENTIAL MARKER
OF NERVE AGENTS
Rajesh Kumar, A. K. Gupta, and M. P. Kaushik
Process Technology Development Division, Defence R & D Establishment,
Gwalior, India
This article describes rapid and efficient surface mediated synthesis of O-alkyl
2-methoxyethyl alkylphosphonates from alkylphosphonic acids and alcohols using
dicyclohexyl carbodiimide (DCC)-Celite as a solid support. These compounds are markers
of nerve agents. 2-Methoxyethyl methylphosphonic acids (2a–d) were reacted with various
alcohols to yield O-alkyl 2-methoxyethyl alkylphosphonates (AMEAPs, 3a–m). This
synthetic method has advantages over other methods in terms of selectivity, shorter reaction
time, high yield, and easy work-up.
Keywords Chemical warfare agents; Chemical Weapons Convention; DCC-Celite; nerve
agents; phosphonates
INTRODUCTION
Chemical Weapons Convention (CWC) is an international disarmament treaty that
came into force in 1997, to which more than 183 countries including India are parties. The
treaty prohibits development, stockpiling, and alleged use of chemical weapons.1 However
after the incident of September 11, 2001, the threat from chemical weapons of mass
destruction has evolved into a serious matter of concern to both military as well as civilian
people. An international organization, known as Organization for Prohibition of Chemical
Weapons (OPCW), is responsible for implementation of the treaty by executing its strict
verification program.1–7 The OPCW is maintaining a network of designated laboratories to
verify the presence of CWC-related chemicals and their markers in the samples collected
by the inspectors from suspected and declared sites.8 Due to the internationally sensitive
nature of the verification process, the analytical performance of designated laboratories
and laboratories seeking designation is periodically evaluated by OPCW by conducting the
official proficiency tests (OPTs).9,10
Thus for successful performance in PTs and for off-site analysis of real samples, the
availability of spectral data is a primary requirement. Consequently, a great deal of work
Received 9 April 2009; accepted 8 November 2009.
The authors thank Ms. Mamta Sharma and Avik Mazumder for NMR analysis.
Address correspondence to M. P. Kaushik, Defence R & D Establishment, Jhansi Road, Gwalior-474002,
(MP), India. E-mail: mpkaushik@rediffmail.com
2064

O-ALKYL 2-METHOXYETHYL ALKYLPHOSPHONATES
2065
O
OH
OH
O
OCH2CH2OCH3
R P
R P
OR1
O
R P
OH
X
O
OCH2CH2OCH3
OCH2CH2OCH3
O
OCH2CH2OCH3
OR1
R P
R P
R= CH3, R1= (CH3)2CHO, X=F (Sarin); R= CH3, R1= (CH3)3CCH(CH3) O, X=F( Soman);
R= CH3, R1= C2H5O, X= SC2H4N (i-C3H7)2 (VX)
Figure 1 Major neutralized products of sarin, soman, and VX by DS-2 solution.
is devoted to developing the spectral database of CRCs.11–13 In spite of global efforts, only
limited spectra of scheduled chemicals are available in various libraries.14 The chemicals
relevant to the convention (CRCs) not only include the popular chemical warfare agents,
but precursors and degradation products are also included in CWC text, which makes the
list of CRCs very exhaustive.
Among the various chemical warfare agents (CWAs), nerve agents such as sarin,
soman, VX, tabun, and their homologues are extremely toxic in nature. In general, DS-2
solution (diethylene tetra amine 78%, methoxy ethanol 20%, and NaOH 2%) is accepted
for their detoxification from the contaminated surfaces. However, when nerve agents (sarin,
soman, VX, and their homologues) are neutralized with DS-2 solution, the major prod-
ucts of decontamination have been identified as O-alkyl 2-methoxyethyl alkylphospho-
nates (AMEAPs), 2-methoxyethyl alkylphosphonic acids (MEAPs), bis(2-methoxyethyl)
alkylphosphonates (BMEAPs), and their alkylphosphonic acids (APAs) (Figure 1).
Since the inception of the project, 24,000 compounds from the sarin and soman
family and 40,000 compounds from the VX family have been estimated for the list of CWC
text.15 Hence, these nerve agents will also give more or less same number of AMEAPs.
Because of this reason, AMEAPs have been considered as important markers of these
nerve agents and are listed in scheduled 2B4 class of the CWC text.1 Probably this is the
reason that they have been spiked quite often in OPTs. The synthesis of their degradation
products (in pure form) by reported methods and including their spectroscopic data in the
database will be a difficult task. In order to resolve such problems, there is a need to develop
efficient and rapid synthetic procedures, which should provide the pure compounds with
minimum effort and time. Rapid synthesis of AMEAPs in pure form is essential to confirm
the structures of analytes revealed by their spectroscopic (e.g., GC-MS, 31P NMR, and GC-
FTIR) data. The perfect match of spectra with synthesized compounds is one of the unique
ways to report the results of analysis, as it does not require much expertise to interpret the
spectra. Furthermore, the spectra and chromatographic data collected by synthesis of pure
compounds are also helpful in on-site and off-site analysis of real samples.7–9
Several methods are reported in the literature for the synthesis of phosphonates;
however the reported methods have several drawbacks such as long reaction times, use
of carcinogenic solvents, harsh reaction conditions, tedious work-up, and the use of chro-
matographic techniques to obtain the pure compounds.16–32

2066
R. KUMAR ET AL.
In recent years, the use of organic–inorganic hybrid immobilized solid support
reagents has received great interest. Such reagents not only simplify the purification process
but are also environmentally friendly.33–40 However, reactions under solvent-free conditions
are some of the more promising alternatives and have recently attracted attention due to leg-
islative enforcement.41,42 The main advantages of such reactions are that they are simpler in
operation and they save energy. The absence of solvent in organic synthesis also makes the
reactions cleaner, prevents solvent wastes, and reduces hazards and toxicity. Furthermore,
from the synthetic viewpoint, these reactions significantly reduce the reaction time, and
workup is also easy.42–48 Efficiency of dicyclohexyl carbodilmide (DCC) and Celite under
operationally simple conditions has prompted us to explore the possibility of this reagent
for the synthesis of AMEAPs.49
RESULTS AND DISCUSSION
In continuation of our ongoing program to develop new reagents and synthetic pro-
cedures for the synthesis of organophosphorus compounds,28,50,51 we report in this arti-
cle a convenient method for the synthesis of O-alkyl 2-methoxyethyl alkylphosphonates
(AMEAPs) by exploiting surface-mediated synthesis at the appropriate temperature. Ini-
tially 2-methoxyethyl alkylphosphonic acids 2a–d were synthesized by DCC-Celite (molar
ratio 1:2)–mediated condensation reaction of the corresponding alkylphosphonic acid and
◦
2-methoxyethanol in a molar ratio of 1:1 at 50–80 C for 60–90 min. The reaction was
monitored by 31P NMR spectroscopy. The 31P NMR results showed quantitative conversion
of the alkylphosphonic acids to the corresponding 2-methoxyethyl alkylphosphonic acids
(MEAPs). After completion of the reaction, the mixture was extracted with ether to yield
crude 2a–d product (Scheme 1).
O
P
O
P
OH
OH
OCH2CH2OCH3
CH3OCH2CH2OH
DCC-Celite
R
R
OH
2a-d
1a-d
i
R = CH3, C2H5, n-C3H7, C3H7
Scheme 1
Compounds 2a–d were reacted with various alcohols in the presence of fresh DCC-
celite by following the same molar ratio and at 100◦C. The reactions were monitored by
TLC and 31P NMR spectroscopy. After completion of the reaction, the reaction mixture
was extracted with ether, and the ether layer was washed with dilute aqueous solution of
sodium carbonate to remove traces of unreacted acid. AMEAPs (3a–m) were obtained in
very good yield (68–80%) (Scheme 2).
The purity of the compounds was checked on silica TLC plate using a chloro-
form/acetone mixture (8:2). Compounds 3a–m were distilled under vacuum and character-
ized by IR, NMR spectroscopy, GC-MS, and elemental analysis. The results are summarized
in Table I.

O-ALKYL 2-METHOXYETHYL ALKYLPHOSPHONATES
Table I Synthesis of O-alkyl 2-methoxyethyl alkylphosphonates 3a–m
2067
Reaction time
(min.)
Yield
(%)a
Bp
31P NMR
(δ ppm)b
3
a
Product
(◦C/mm Hg)
70
85
90
45
55
60
85
95
100
76.5
73.4
72.5
80.5
77.6
69.7
70.8
73.5
77.3
145/0.5
147/0.5
160/0.5
142/0.5
145/0.5
150/0.5
150/0.5
162/0.5
165/0.5
31.4
31.2
31.2
35.8
35.3
34.7
34.9
34.3
35.6
b
c
d
e
f
g
h
i
j
110
110
71.6
68.4
Oil
Oil
33.0
32.7
k
l
120
120
70.5
70.3
Oil
Oil
32.3
32.2
m
aIsolated yield.
b31P NMR spectra were recorded in CDCl3 at 162 MHz.

2068
R. KUMAR ET AL.
O
OCH2CH2OCH3
OR1
R1OH and DCC-Celite
R
P
2a-d
3a-m
R = CH3, C2H5, n-C3H7, iC3H7
R1 = CH3, C2H5, n-C3H7, iC3H7, C4H9,
iC4H9, C5H11, C6H11, C6H13
Scheme 2
CONCLUSION
In conclusion, we have developed a rapid and efficient method for the synthesis of O-
alkyl 2-methoxyethyl alkylphosphonates 3a–m with excellent yields. The main advantage
of this method is that reactions were found to be clean and had operational simplicity.
Column chromatography was not required to get the pure products, which makes the
method more attractive for organic chemists.
EXPERIMENTAL
Melting points were determined on a hot stage microscope and are uncorrected. IR
spectra were recorded with a Bruker FT-IR spectrometer model Tensor 27 on KBr disk,
and solid compounds were analyzed by making KBr pellets. 1H, 13C, and 31P NMR spectra
were recorded in CDCl3 with Bruker DPX Avance FT-NMR spectrometer at 400, 100,
1
and 162 MHz, respectively, using tetramethylsilane as internal standard for H, 13C, and
85% H3PO4 as external standard for 31P NMR. A Chemito GC model 1000 instrument
was used with a flame ionization detector (FID). A capillary column (30 m × 0.25 mm
LD-BP5) packed with 5% phenyl and 95% dimethyl polysiloxane (SGE) coated on fused
silica was employed. The injection port and detector block were maintained at 280◦C and
260◦C, respectively, and the column oven was at programmed temperature profile starting
at 50◦C and ramped up to 280◦C at 25◦C/min. Nitrogen was used as carrier gas (at a flow
rate of 30 mL/min). Air for FID was supplied at 300 mL/min and hydrogen at 30 mL/min.
In all analyses, 0.1 µL sample was injected, and peaks were recorded on an Iris32 data
acquisition station. The GC-MS analyses were performed in EI (70 eV) in full scan mode
with an Agilent 6890 GC equipped with a model 5973 mass selective detector (Agilent
Technologies, USA). An SGE BPX5 capillary column with 30 m length × 0.32 mm internal
diameter × 0.25 µm film thickness was used with temperature program of 80◦C (2 min)
20◦C/min 280◦C (3 min). Helium was used as the carrier gas at a constant flow rate of 1.2
mL/min. The samples were analyzed in splitless mode at injection temperature.
Synthesis of 2-Methoxyethyl Alkylphosphonic Acids (2):
General Procedure
Alkylphosphonic acid (0.1 mol), DCC (20.6 g, 0.1 mol), 2-methoxyethanol (7.6 g, 0.1
mol), and celite (6.4 g, 0.2 mol) were ground with a pestle in a mortar at room temperature
followed by heating 50–80◦C for a period of 60–90 min. The progress of the reaction

O-ALKYL 2-METHOXYETHYL ALKYLPHOSPHONATES
2069
was monitored by 31P NMR after drawing a few milligrams of the reaction mixture and
extracting with ether. After the disappearance of the signal of the alkylphosphonic acid
in the 31P NMR spectrum, the reaction mass was washed with ether, and the solvent was
evaporated. The residue afforded the crude 2-methoxyethyl alkylphosphonic acid, which
was used for the next step without further purification.
2-Methoxyethyl methylphosphonic acid (2a). IR (KBr): 695 (P C), 1090,
1
1150 (P O C), 1230 (P O), 2890 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
31.8; 1H NMR (400 MHz, CDCl3): δ = 1.54 (d, 2JPH = 17.6 Hz, 3H, CH3), 3.39 (s, 3H,
3
CH3), 3.62 (t, J = 4.9 Hz, 2H, CH2), 4.10 (dt, JPH = 8.1 Hz, JHH = 6.4 Hz, 2H, CH2),
8.53 (s, 1H, OH); 13C{ H} NMR (100 MHz, CDCl3): δ = 11.5 (d, 1JPC = 146 Hz, CH3),
1
58.9 (CH3), 64.4 (d, 3JPC = 6.3 Hz, CH2), 71.8 (d, 2JPC = 5.8 Hz, CH2).
2-Methoxyethyl ethylphosphonic acid (2b). IR (KBr): 693 (P C), 1085, 1150
(P O C), 1240 (P O), 2883 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ = 33.6;
1
1H NMR (400 MHz, CDCl3): δ = 1.05 (dt, 3JPH = 19.4 Hz, JHH = 8.3 Hz, 3H, CH3), 1.59
(dq, 2JPH = 17.9 Hz, JHH = 6.9 Hz, 2H, CH2), 3.26 (s, 3H, CH3), 3.48 (t, J = 7.3 Hz, 2H,
CH2), 3.95 (dt, 3JPH = 7.3 Hz, JHH = 5.8 Hz, 2H, CH2), 8.53 (s, 1H, OH); 13C{ H} NMR
1
(100 MHz, CDCl3): δ = 9.5 (d, 2JPC = 6.5 Hz, CH3), 18.6 (d, 1JPC = 139 Hz, CH2), 58.0
(CH3), 63.1 (d, 3JPC = 6.3 Hz, CH2), 71.3 (d, 2JPC = 5.8 Hz, CH2).
2-Methoxyethyl propylphosphonic acid (2c). IR(KBr): 702(P-C), 1090, 1153
(P O C), 1235 (P O), 2880 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ = 34.2;
1
1H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.4 Hz, 3H, CH3), 1.21 (dq, 3JPH = 15.6 Hz,
JHH = 7.1 Hz, 2H, CH2), 1.55 (dt, 2JPH = 17.9 Hz, JHH = 6.7 Hz, 2H, CH2), 3.23 (s, 3H,
3
CH3), 3.45 (t, J = 7.3 Hz, 2H, CH2), 4.05 (dt, JPH = 7.3 Hz, JHH = 6.2 Hz, 2H, CH2),
8.50 (s, 1H, OH); 13C{ H} NMR (100 MHz, CDCl3): δ = 9.5 (d, JPC = 6.5 Hz, CH3),
1
3
11.3 (d, 2JPC = 7.3 Hz, CH2), 18.7 (d, 1JPC = 139.8 Hz, CH3), 57.9 (CH3), 63.0 (d, 3JPC
=
6.4 Hz, CH2), 71.2 (d, 2JPC = 5.9 Hz, CH2).
2-Methoxyethyl isopropylphosphonic acid (2d). IR (KBr): 698 (P C), 1093,
1150 (P O C), 1245 (P O), 2865 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ
1
= 34.9; 1H NMR (400 MHz, CDCl3): δ = 1.17 (dd, 3JPH = 21.4 Hz, JHH = 7.5 Hz, 6H,
CH3), 2.05 (d of septets, 2JPH = 17.6 Hz, JHH = 6.9 Hz, 1H, CH), 3.20 (s, 3H, CH3), 3.42
(t, J = 7.3 Hz, 2H, CH2), 3.95 (dt, 3JPH = 7.3 Hz, JHH = 5.4 Hz, 2H, CH2), 8.53 (s, 1H,
OH); 13C{ H} NMR (100 MHz, CDCl3): δ = 14.4 (d, 2JPC = 10.0 Hz, CH3), 21.1 (d, 1JPC
1
= 144.2 Hz, CH), 58.0 (CH3), 63.1 (d, 3JPC = 6.3 Hz, CH2), 71.3 (d, 2JPC = 5.8 Hz, CH2).
Synthesis of O-Alkyl 2-Methoxyethyl Alkylphosphonates (3):
General Procedure
2-Methoxyethyl alkylphosphonic acid (0.03 mol), DCC (6.18 g, 0.03 mol), alcohol
(0.03 mol), and Celite (1.924 g, 0.06 mol) were ground with a pestle in a mortar at 50–100◦C
for 45–120 min (Table I). The progress of the reaction was monitored by TLC and 31P NMR
spectroscopy after drawing a few milligrams of the reaction mixture and extracting with
ether. After the disappearance of the signal of the 2-methoxyethyl alkylphosphonic acid
in the 31P NMR spectrum, the reaction mass was extracted with ether (3 × 25 mL). The
ether layer was washed with dilute aqueous sodium carbonate solution to remove the traces
of free acids. The ether layer was collected and dried over anhydrous Na2SO4. It was
filtered and washed with ether. The filtrate and washings were collected, and the solvent

2070
R. KUMAR ET AL.
was evaporated. The residue was distilled under vacuum to afford the pure compound 3a–m
(68.4–80.5%) (Table I).
O-Propyl 2-methoxyethyl methylphosphonate (3a). Anal. Calcd.
C7H17O4P: C, 42.86; H, 8.73. Found: C, 42.85; H, 8.70%. IR (KBr): 703 (P C),
1
1085, 1156 (P O C), 1229 (P O), 2870 (C H) cm−1
;
31P{ H} NMR (162 MHz,
CDCl3): δ = 31.4; 1H NMR (400 MHz, CDCl3): δ = 0.96 (t, J = 7.4 Hz, 3H, CH3), 1.51
2
(d, JPH = 17.6 Hz, 3H, CH3), 1.70 (sextet, J = 7.4 Hz, 2H, CH2), 3.40 (s, 3H, CH3),
3.60 (t, J = 7.6 Hz, 2H, CH2), 4.02 (dt, 3JPH = 9.9 Hz, JHH = 6.4 Hz, 2H, CH2), 4.20 (dt,
3JPH = 8.4 Hz, JHH = 5.9 Hz, 2H, CH2); 13C{ H} NMR (100 MHz, CDCl3): δ = 10.1
1
1
3
(CH3), 11.1 (d, JPC = 145.0 Hz, CH3), 23.8 (d, JPC = 5.2 Hz, CH2), 58.7 (CH3), 64.4
3
2
2
(d, JPC = 6.1 Hz, CH2), 67.1 (d, JPC = 6.4 Hz, CH2), 71.8 (d, JPC = 5.8 Hz, CH2);
GC-MS (EI,%): 197 (M+H+), 166, 155 (3.5), 139 (27.4), 125 (30.5), 111 (15.3), 97 (100),
79 (43.7), 58 (88.5), 45 (51.3).
O-Butyl 2-methoxyethyl methylphosphonate (3b). Anal. Calcd. C8H19O4P:
C, 45.79; H, 9.11. Found: C, 45.76; H, 9.10%. IR (KBr): 696 (P C), 1083, 1155 (P O C),
1
1235 (P O), 2880 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ = 31.2; 1H NMR
(400 MHz, CDCl3): δ = 0.96 (t, J = 7.3 Hz, 3H, CH3), 1.50 (d, 2JPH = 17.6 Hz, 3H, CH3),
1.75 (t, J = 7.1 Hz, 4H, CH2), 3.35 (s, 3H, CH3), 3.61 (t, J = 7.5 Hz, 2H, CH2), 4.0 (dt,
3JPH = 9.8 Hz, JHH = 5.8 Hz, 2H, CH2), 4.25 (dt, 3JPH = 8.3 Hz, JHH = 5.5 Hz, 2H, CH2);
13C{ H} NMR (100 MHz, CDCl3): δ = 10.1 (CH3), 11.1 (d, 1JPC = 145.0 Hz, CH3), 21.4
1
(CH2), 23.8 (d, 3JPC = 5.5 Hz, CH2), 58.7 (CH3), 64.3 (d, 3JPC = 6.1 Hz, CH2), 67.2 (d,
2JPC = 6.4 Hz, CH2), 71.7 (d, JPC = 5.9 Hz, CH2); GC-MS (EI,%): 211 (M+H+), 165
2
(9.4), 155 (11.7), 137 (17.6), 125 (28.7), 111 (11.7), 97 (100), 79 (21.6), 58 (73.7), 45
(39.5).
O-Pentyl 2-methoxyethyl methylphosphonate (3c). Anal. Calcd.
C9H21O4P: C, 48.21; H, 9.44. Found: C, 48.20; H, 9.45%. IR (KBr): 694 (P C),
1
1089, 1152 (P O C), 1237 (P O), 2885 (C H) cm−1
;
31P{ H} NMR (162 MHz,
1
CDCl3): δ = 31.2; H NMR (400 MHz, CDCl3): δ = 0.93 (t, J = 7.3 Hz, 3H, CH3),
1.39 (dt, J = 7.2 Hz, JHH = 8.1 Hz, 2H, CH2), 1.52 (d, 2JPH = 17.5 Hz, 3H, CH3), 1.70
(quintet, J = 7.2 Hz, 4H, CH2), 3.38 (s, 3H, CH3), 3.61 (t, J = 7.6 Hz, 2H, CH2), 4.00
(dt, 3JPH = 9.8 Hz, JHH = 6.4 Hz, 2H, CH2), 4.25 (dt, 3JPH = 8.3 Hz, JHH = 6.7 Hz, 2H,
CH2); 13C{ H} NMR (100 MHz, CDCl3): δ = 10.2 (CH3), 11.2 (d, 1JPC = 145 Hz, CH3),
1
21.3 (CH2), 22.8 (CH2), 23.9 (d, 3JPC = 6.2 Hz, CH2), 58.4 (CH3), 64.3 (d, 3JPC = 6.1 Hz,
2
2
CH2), 66.9 (d, JPC = 6.4 Hz, CH2), 71.7 (d, JPC = 5.9 Hz, CH2); GC-MS (EI,%): 225
(M+H+), 181(3.1) 167(8.9), 155 (18.5), 137 (8.45), 125 (35.3), 111 (10.8), 97 (100), 79
(15.8), 71 (9.6) 58 (73.8), 45 (40.3).
O-Methyl 2-methoxyethyl isopropylphosphonate (3d). Anal. Calcd.
C7H17O4P: C, 42.86; H, 8.73. Found: C, 42.85; H, 8.70%. IR (KBr): 698 (P C), 1085,
1
1155 (P O C), 1245 (P O), 2875 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3):
1
3
δ = 35.8; H NMR (400 MHz, CDCl3): δ = 1.17 (dd, JPH = 21.4 Hz, JHH = 7.8 Hz,
6H, CH3), 2.05 (d of septets, 2JPH = 17.9 Hz, JHH = 7.1 Hz, 1H, CH), 3.40 (s, 3H, CH3),
3.60 (t, J = 7.6 Hz, 2H, CH2), 4.02 (dt, 3JPH = 9.9 Hz, JHH = 6.6 Hz, 3H, CH3), 4.12 (dt,
3JPH = 8.4 Hz, JHH = 5.7 Hz, 2H, CH2); 13C{ H} NMR (100 MHz, CDCl3): δ = 14.4 (d,
1
2JPC = 10.0 Hz, CH3), 21.2 (d, 1JPC = 144.2 Hz, CH), 58.3 (CH3), 64.3 (d, 3JPC = 6.1 Hz,
2
2
CH2), 66.9 (d, JPC = 6.5 Hz, CH3), 71.5 (d, JPC = 6.0 Hz, CH2); GC-MS (EI,%): 195
(M+H+), 181 (3.5), 166 (11.8), 155 (35.9), 139 (87.3), 125 (21.9), 109 (15.3), 96 (10.0),
79 (83.1), 58 (100), 45 (41.3).

O-ALKYL 2-METHOXYETHYL ALKYLPHOSPHONATES
2071
O-Ethyl 2-methoxyethyl isopropylphosphonate (3e). Anal. Calcd.
C8H19O4P: C, 45.79; H, 9.11. Found: C, 45.76; H, 9.10%. IR (KBr): 705 (P C), 1085,
1
1153 (P O C), 1235 (P O), 2855 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
35.3; 1H NMR (400 MHz, CDCl3): δ = 1.15 (dd, 3JPH = 21.5, JHH = 9.3 Hz, 6H, CH3),
1.21 (t, J = 7.5 Hz, 3H, CH3), 2.02 (d of septets, 2JPH = 17.8 Hz, JHH = 7.4 Hz, 1H, CH),
3
3.45 (s, 3H, CH3), 3.70 (t, J = 7.6 Hz, 2H, CH2), 4.07 (dt, JPH = 10.3 Hz, JHH = 6.3
Hz, 2H, CH2), 4.12 (dq, JPH = 8.5 Hz, JHH = 5.4 Hz, 3H, CH3); 13C{ H} NMR (100
MHz, CDCl3): δ = 14.3 (d, 2JPC = 10.0 Hz, CH3), 16.4 (d, 3JPC = 5.4 Hz, CH3), 21.1 (d,
1JPC = 144.2 Hz, CH), 58.6 (CH3), 64.3 (d, 3JPC = 6.1 Hz, CH2), 67.0 (d, 3JPC = 6.4 Hz,
CH2), 71.7 (d, 2JPC = 5.8 Hz, CH2); GC-MS (EI,%): 211 (M+H+), 180 (13.5), 167 (27.8),
155 (61.5), 139 (25.1), 125 (65.4), 107 (17.3), 93 (11.9), 79 (8.1), 58 (100), 45 (44.7), 43
(43.6).
3
1
O-Isopropyl 2-methoxyethyl isopropylphosphonate (3f). Anal. Calcd.
C9H21O4P: C, 48.21; H, 9.44. Found: C, 48.20; H, 9.44%. IR (KBr): 695 (P C), 1085,
1
1150 (P O C), 1235 (P O), 2855 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
34.7; 1H NMR (400 MHz, CDCl3): δ = 1.10 (dd, 3JPH = 21.2, JHH = 7.1 Hz, 6H, CH3),
2
1.20 (d, J = 8.0 Hz, 6H, CH3), 2.05 (d of septets, JPH = 17.7 Hz, JHH = 6.8 Hz, 1H,
CH), 3.40 (s, 3H, CH3), 3.75 (t, J = 7.6 Hz, 2H, CH2), 4.00 (d of septets, 3JPH = 10.1 Hz,
JHH = 6.4 Hz, 1H, CH), 4.15 (dt, 3JPH = 8.7 Hz, JHH = 7.3 Hz, 2H, CH2); 13C{ H} NMR
1
(100 MHz, CDCl3): δ = 14.3 (d, 2JPC = 10.0 Hz, CH3), 17.3 (CH3), 21.1 (d, 1JPC = 144.2
Hz, CH), 58.6 (CH3), 64.3 (d, 3JPC = 6.1 Hz, CH2), 67.3 (d, 2JPC = 6.4 Hz, CH), 71.7 (d,
2JPC = 5.8 Hz, CH2); GC-MS (EI,%): 225 (M + H+), 194 (5.8), 183 (7.6), 165 (21.7),
152 (10.2), 139 (30.6), 125 (100), 113 (11.7), 107 (10.3), 79 (8.3), 65 (15.6), 58 (63.9), 43
(44.6).
O-Isobutyl 2-methoxyethyl isopropylphosphonate (3g). Anal. Calcd.
C10H23O4P: C, 50.41; H, 9.73. Found: C, 50.40; H, 9.75%. IR (KBr): 702 (P C), 1075,
1
1150 (P O C), 1245 (P O), 2848 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3):
δ = 34.9; 1H NMR (400 MHz, CDCl3): δ = 1.10 (d, J = 8.0 Hz, 6H, CH3), 1.15 (dd, 3JPH
=
21.5, JHH = 6.8 Hz, 6H, CH3), 1.73 (quintet, J = 7.6 Hz, 1H, CH), 2.10 (d of septets,
2JPH = 17.6 Hz, JHH = 6.1 Hz, 1H, CH), 3.45 (s, 3H, CH3), 3.70 (t, J = 7.3 Hz, 2H, CH2),
4.05 (dt, 3JPH = 10.3 Hz, JHH = 6.9 Hz, 2H, CH2), 4.12 (dt, 3JPH = 8.7 Hz, JHH = 5.6 Hz,
2H, CH2); 13C{ H} NMR (100 MHz, CDCl3): δ = 11.5 (CH3), 14.3 (d, 2JPC = 10.0 Hz,
1
CH3), 18.2 (d, 3JPC = 4.2 Hz, CH), 21.1 (d, JPC = 144.2 Hz, CH), 58.6 (CH3), 64.3 (d,
1
3JPC = 6.1 Hz, CH2), 67.0 (d, 2JPC = 6.4 Hz, CH2), 71.7 (d, 2JPC = 5.8 Hz, CH2); GC-MS
(EI,%): 239 (M+H+), 223 (3.7), 208 (2.9), 195 (5.3), 183 (10.4), 165 (11.2), 153 (11.3),
139 (22.7), 125 (100), 113 (7.5), 79 (8.3), 65 (10.2), 58 (43.7), 43(25.4).
O-Pentyl 2-methoxyethyl isopropylphosphonate (3h). Anal. Calcd.
C11H25O4P: C, 52.37; H, 9.99. Found: C, 52.35; H, 10.00%. IR (KBr): 698 (P C), 1080,
1
1155 (P O C), 1235 (P O), 2865 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ
= 34.3; 1H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.4 Hz, 3H, CH3), 1.15 (dd, 3JPH
= 21.4, JHH = 7.7 Hz, 6H, CH3), 1.20 (t, J = 7.3 Hz, 2H, CH2), 1.39 (q, J = 7.0 Hz, 2H,
CH2), 1.75 (q, J = 7.4 Hz, 2H, CH2), 2.05 (d of septets, 2JPH = 17.8 Hz, JHH = 6.2 Hz,
1H, CH), 3.38 (s, 3H, CH3), 3.61 (t, J = 7.6 Hz, 2H, CH2), 4.03 (dt, 3JPH = 9.8 Hz, JHH
=
7.2 Hz, 2H, CH2), 4.25 (dt, 3JPH = 8.3 Hz, JHH = 5.7 Hz, 2H, CH2); 13C{ H} NMR (100
1
MHz, CDCl3): δ = 10.1 (CH3), 11.1 (d, 2JPC = 10.1 Hz, CH3), 18.8 (CH2), 21.1 (d, 1JPC
=
144.2 Hz, CH), 22.8 (CH2), 23.8 (d, 3JPC = 5.4 Hz, CH2), 58.6 (CH3), 64.5 (d, 3JPC = 6.1
2
2
Hz, CH2), 67.1 (d, JPC = 6.4 Hz, CH2), 71.6 (d, JPC = 5.9 Hz, CH2); GC-MS (EI,%):

2072
R. KUMAR ET AL.
253 (M+H+), 237 (2.8), 222 (5.7), 209 (10.5), 183 (20.3) 165 (7.3), 139 (25.4), 125 (100),
113 (8.3), 79 (6.4), 58 (9.4), 43 (44.7).
O-Cyclohexyl 2-methoxyethyl isopropylphosphonate (3i). Anal. Calcd.
C12H25O4P: C, 54.53; H, 9.53. Found: C, 54.50; H, 9.50%. IR (KBr): 694 (P C), 1089,
1
1152 (P O C), 1237 (P O), 2885 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
1
35.6; H NMR (400 MHz, CDCl3): δ = 1.12 (dd, J = 7.4 Hz, JHH = 6.7 Hz, 2H, CH2),
3
1.15 (dd, JPH = 21.4, JHH = 7.4 Hz, 6H, CH3), 1.25 (dt, J = 7.5 Hz, JHH = 7.8 Hz,
4H, CH2), 1.85 (dt, J = 7.5 Hz, JHH = 7.8 Hz, 4H, CH2), 2.10 (d of septets, 2JPH = 17.8
Hz, JHH = 6.1 Hz, 1H, CH), 3.39 (s, 3H, CH3), 3.60 (t, J = 7.6 Hz, 2H, CH2), 4.12 (dt,
3JPH = 8.3 Hz, JHH = 8.1 Hz, 2H, CH2), 4.42 (dd, 3JPH = 7.3 Hz, JHH = 5.4 Hz, 1H, CH);
13C{ H} NMR (100 MHz, CDCl3): δ = 14.3 (d, JPC = 10.0 Hz, CH3), 21.1 (d, JPC
=
1
2
1
144.2 Hz, CH), 23.6 (CH2), 25.2 (CH2), 33.4 (d, 3JPC = 5.5 Hz, CH2), 58.9 (CH3), 64.2 (d,
3JPC = 6.1 Hz, CH2), 71.1 (d, 2JPC = 6.4 Hz, CH2), 75.0 (d, 2JPC = 5.9 Hz, CH); GC-MS
(EI,%): 265 (M+H+), 235 (3.6), 221 (6.9), 207 (2.5), 183 (28.3) 165 (5.2), 139 (15.3), 125
(100), 113 (5.8), 83 (10.2), 59 (30.1), 41 (19.7).
O-1,3-Dimethylbutyl 2-methoxyethyl ethylphosphonate (3j). Anal. Calcd.
C11H25O4P: C, 52.37; H, 9.99. Found: C, 52.40; H, 9.98%. IR (KBr): 695 (P C), 1089,
1
1150 (P O C), 1238 (P O), 2845 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
33.0; 1H NMR (400 MHz, CDCl3): δ = 0.95 (d, J = 7.4 Hz, 6H, CH3), 1.05 (sextet, J =
7.2 Hz, 1H, CH), 1.17 (dt, 3JPH = 20.2 Hz, JHH = 6.7 Hz, 3H, CH3), 1.20 (dd, J = 7.4 Hz,
2
JHH = 6.6 Hz, 2H, CH2), 1.77 (dq, JPH = 17.6 Hz, JHH = 7.5 Hz, 2H, CH2), 2.11 (dd,
JHH = 6.3 Hz, 3H, CH3), 3.38 (s, 3H, CH3), 3.61 (t, J = 7.6 Hz, 2H, CH2), 4.0 (dt, 3JPH
=
9.8 Hz, JHH = 7.4 Hz, 2H, CH2), 4.25 (dt, 3JPH = 8.3 Hz, JHH = 6.7 Hz, 1H, CH); 13C{ H}
NMR (100 MHz, CDCl3): δ = 9.9 (CH3), 10.4 (CH), 10.6 (d, 2JPC = 7.0 Hz, CH3), 19.5
(d, 1JPC = 143.6 Hz, CH2), 21.4 (CH2), 23.8 (d, 3JPC = 5.8 Hz, CH3), 58.6 (CH3), 64.3 (d,
3JPC = 6.1 Hz, CH2), 67.9 (d, 2JPC = 6.4 Hz, CH2), 71.6 (d, 2JPC = 5.9 Hz, CH); GC-MS
(EI,%): 253 (M+H+), 169 (19.4), 151 (71.5), 138 (11.6), 125 (7.5), 111 (100), 93 (7.9), 79
(4.5), 58 (33.7), 43 (26.5).
1
O-1-Methylpentyl 2-methoxyethyl ethylphosphonate (3k). Anal. Calcd.
C11H25O4P: C, 52.37; H, 9.99. Found: C, 52.35; H, 10.00%. IR (KBr): 703 (P C), 1085,
1
1150 (P O C), 1250 (P O), 2867 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
1
3
32.7; H NMR (400 MHz, CDCl3): δ = 0.96 (t, J = 7.3 Hz, 3H, CH3), 1.17 (dt, JPH
=
20.2 Hz, JHH = 8.3 Hz, 3H, CH3), 1.38 (q, J = 7.4 Hz, 2H, CH2), 1.75 (t, J = 7.4 Hz, 4H,
CH2), 1.77 (dq, 2JPH = 17.6 Hz, JHH = 7.8 Hz, 2H, CH2), 2.05 (q, J = 6.2 Hz, 3H, CH3),
3.38 (s, 3H, CH3), 3.61 (t, J = 7.6 Hz, 2H, CH2), 4.12 (dt, 3JPH = 9.8 Hz, JHH = 5.9 Hz,
2H, CH2), 4.25 (dq, JPH = 8.3 Hz, JHH = 5.3 Hz, 1H, CH); 13C{ H} NMR (100 MHz,
3
1
CDCl3): δ = 10.1 (CH3), 11.7 (d, 2JPC = 7.0 Hz, CH3), 19.5 (d, 1JPC = 143.6 Hz, CH2),
3
21.4 (CH2), 22.8 (CH2), 23.8 (CH2), 39.2 (d, JPC = 7.6 Hz, CH3), 58.7 (CH3), 64.4 (d,
3JPC = 6.1 Hz, CH2), 67.1 (d, 2JPC = 6.4 Hz, CH2), 71.8 (d, 2JPC = 5.9 Hz, CH); GC-MS
(EI,%): 253 (M+H+), 181 (3.1) 169 (18.3), 151 (88.5), 138 (8.45), 125 (7.3), 111 (100),
93 (10.2), 79 (5.8), 71 (9.6) 58 (33.7), 45 (20.3).
O-1,3-Dimethylbutyl 2-methoxyethyl propylphosphonate (3l). Anal.
Calcd. C12H27O4P: C, 54.12; H, 10.22. Found: C, 54.10; H, 10.20%. IR (KBr): 695
1
(P C), 1090, 1155 (P O C), 1235 (P O), 2865 (C H) cm−1
;
31P{ H} NMR (162
MHz, CDCl3): δ = 32.3; 1H NMR (400 MHz, CDCl3): δ = 0.96 (d, J = 7.2 Hz, 6H, CH3),
1.05 (sextet, J = 7.2 Hz, 1H, CH), 1.07 (t, J = 7.2 Hz, 3H, CH3), 1.18 (dq, 3JPH = 20.2
2
Hz, JHH = 7.3 Hz, 2H, CH2), 1.20 (q, J = 7.4 Hz, 2H, CH2), 1.77 (dt, JPH = 17.6 Hz,

O-ALKYL 2-METHOXYETHYL ALKYLPHOSPHONATES
2073
JHH = 6.9 Hz, 2H, CH2), 2.11 (q, JHH = 8.1 Hz, 3H, CH3), 3.38 (s, 3H, CH3), 3.60
3
(t, J = 7.6 Hz, 2H, CH2), 4.05 (dt, JPH = 9.8 Hz, JHH = 7.2 Hz, 2H, CH2), 4.25 (dt,
1
3JPH = 8.3 Hz, JHH = 6.8 Hz, 1H, CH); 13C{ H} NMR (100 MHz, CDCl3): δ = 9.9 (CH3),
3
2
1
10.4 (CH), 11.1 (d, JPC = 6.2 Hz, CH3), 12.4 (d, JPC = 7.0 Hz, CH2), 19.5 (d, JPC
=
=
3
3
143.6 Hz, CH3), 21.4 (CH2), 33.3 (d, JPC = 7.0 Hz, CH3), 58.7 (CH3), 64.4 (d, JPC
6.1 Hz, CH2), 70.2 (d, 2JPC = 6.4 Hz, CH2), 73.1 (d, 2JPC = 5.9 Hz, CH); GC-MS (EI,%):
267 (M+H+), 183 (15.3), 165 (55.3), 152 (11.5), 139 (9.6), 125 (100), 110 (3.7), 96 (7.9),
69 (4.5), 58 (33.7), 43 (26.5).
O-1-Methylpentyl 2-methoxyethyl propylphosphonate (3m). Anal. Calcd.
C12H27O4P: C, 54.12; H, 10.22. Found: C, 54.10; H, 10.20%. IR (KBr): 697(P C), 1085,
1
1140 (P O C), 1254 (P O), 2875 (C H) cm−1
;
31P{ H} NMR (162 MHz, CDCl3): δ =
32.2; 1H NMR (400 MHz, CDCl3): δ = 0.95 (t, J = 7.2 Hz, 3H, CH3), 1.07 (t, J = 7.2 Hz,
3
3H, CH3), 1.17 (dq, JPH = 20.2 Hz, JHH = 7.4 Hz, 2H, CH2), 1.39 (q, J = 7.4 Hz, 2H,
2
CH2), 1.75 (sextet, J = 7.4 Hz, 4H, CH2), 1.77 (dt, JPH = 17.6 Hz, JHH = 6.6 Hz, 2H,
CH2), 2.15 (q, J = 8.2 Hz, 3H, CH3), 3.38 (s, 3H, CH3), 3.61 (t, J = 7.6 Hz, 2H, CH2), 4.0
(dt, 3JPH = 8.8 Hz, JHH = 5.8 Hz, 2H, CH2), 4.25 (dq, 3JPH = 7.3 Hz, JHH = 6.1 Hz, 1H,
CH); 13C{ H} NMR (100 MHz, CDCl3): δ = 10.1 (CH3), 11.1 (d, 3JPC = 6.0 Hz, CH3),
1
2
1
17.6 (d, JPC = 7.0 Hz, CH2), 19.5 (d, JPC = 143.6 Hz, CH2), 21.4 (CH2), 22.8 (CH2),
23.8 (CH2), 39.6 (d, 3JPC = 6.0 Hz, CH3), 58.7 (CH3), 64.4 (d, 3JPC = 6.1 Hz, CH2), 69.0
(d, 2JPC = 6.4 Hz, CH2), 73.3 (d, 2JPC = 5.9 Hz, CH); GC-MS (EI,%): 267 (M+H+), 183
(13.1) 165 (68.3), 152 (8.5), 139 (8.4), 125 (100), 107 (4.7), 93 (10.2), 79 (5.8), 69 (5.6)
58 (35.3), 45 (28.6).
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