Microwave synthesis of trichlorfon and its analogues

Article abstract of DOI:10.1080/10426500490475184

The synthesis of dialkyl-(2,2,2-trichloro-1-Hydroxyethyl) phosphonates using dialkyl hydrogen phosphite and chloral hydrate under solvent-free condition by microwave irradiation is reported. The products were chrachetrized using ¹H NMR, ¹³

Full text of DOI:10.1080/10426500490475184

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Phosphorus, Sulfur, and Silicon
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MICROWAVE SYNTHESIS
OF TRICHLORFON AND ITS
ANALOGUES
a
a
Abdollah Javidan & A. R. Banan
a
Department of Chemistry, Imam Hossein
University , Tehran, I. R. Iran
Published online: 16 Aug 2010.
To cite this article: Abdollah Javidan & A. R. Banan (2004) MICROWAVE SYNTHESIS OF
TRICHLORFON AND ITS ANALOGUES, Phosphorus, Sulfur, and Silicon and the Related
Elements, 179:11, 2253-2258, DOI: 10.1080/10426500490475184
To link to this article: http://dx.doi.org/10.1080/10426500490475184
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Phosphorus, Sulfur, and Silicon, 179:2253–2258, 2004
Copyright ꢀC Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500490475184
MICROWAVE SYNTHESIS OF TRICHLORFON
AND ITS ANALOGUES
Abdollah Javidan and A. R. Banan
Department of Chemistry, Imam Hossein University,
Tehran, I. R. Iran
(
Received August 26, 2003; accepted April 8, 2004)
The synthesis of dialkyl-(2,2,2-trichloro-1-Hydroxyethyl) phosphonates
using dialkyl hydrogen phosphite and chloral hydrate under solvent-
free condition by microwave irradiation is reported. The products were
1
13
31
chrachetrized using H NMR, C NMR, and P NMR spectroscopy.
Keywords: Anticholinestrase; insecticide; microwave; organophospho-
rus compounds; trichlorfon
INTRODUCTION
Dialkyl-(2,2,2-trichloro-1-hydroxyethyl)phosphonates are important
from the point of view of biologic activity, and the agrochemical and
medicine industries, for example, trichlorfon (3a) or dimethyl-2,2,2-
1
−4
tricholoro-1-hydroxyethyl phosphonate is a pesticide.
Since this com-
pound is less toxic than DDT, it is a good candidate to replace for DDT.
Trichlorfon, which is well known as metrifonate in the medicine indus-
try, is under investigation as an affecting drug for alzheimer’s disease
and anticholinestrase.5
In recent years, there has been growing interest in the application
of microwave irradiation in chemical reaction enhancement because of
6
−8
its cleaner reactions, decreased reaction time, and easier workup.
In continuation of our ongoing efforts in this area, for the above rea-
sons, and in view of our general interest in microwave synthesis, we
wish to report here the synthesis of these organophosphorus compounds
using microwave irradiation. This procedure is a general method for
We thank the Basic Science Research Center of I.H.U for financial support of this
work. We also thank Dr. A. Hajipour and Dr. A. Moghimi for their helpful discussions.
Address correspondence to Abdollah Javidan, Department of Chemistry, Imam Hos-
sein University, P.O. Box 16575-347, Tehran, I. R. Iran. E-mail: ajavidan@ihu.ac.ir
2
253

2
254
A. Javidan and A. R. Banan
synthesis of dialkyl-2,2,2-tricholoro-1-hydroxyethyl phosphonates 3a–
c by microwave irradiation, which in previous preparations required
heating starting materials for several hours in the reflux condition. The
data obtained show that the reaction time can be reduced to minutes
in good yields.
RESULTS AND DISCUSSION
For our study we worked with neat dialkylphosphites 1 and chloral
hydrate 2 using a domestic microwave oven under solvent-free condi-
tions in the presence of alumina or silica gel. The synthetic conven-
tional method for these compounds was the same as previously re-
ported procedures.9
−12
The reactions are completed within minutes and
in good-to-excellent yields (65–93%, Table I). To evaluate the effect of
microwave irradiation, we tried several experiments on compounds 3a
(
3, 6, 9, and 12 min). We observed that increasing the reaction time
had no significant effect on the yields to product. In addition, when we
exposed the reaction mixture to microwave irradiation for 30 min the
product decomposed.
SCHEME 1
The structure of the products was assigned with H NMR, 13C NMR,
1
3
1
and P NMR spectroscopic analysis and comparison with authentic
1
3−15
samples.
The existence of signal at 18.84 ppm and disappearance
31
1
of the signal at 11 ppm in the P-{ H} NMR spectrum of crude product
1
shows the presence of trichlorfon 3a. The H NMR spectrum showed
two doublets at 3.89 and 3.93 ppm, confirming the presence of two di-
asteretopic methoxy groups.
The signal for methine proton of trichlorfon appeared as a doublet
2
at 4.54 ppm with J = 15. JP−H = 11.5 Hz. With respect to the relation-
2
ship between the magnitude of JP−H and dihedral angle observed in

Microwave Synthesis of Trichlorfon and Derivatives
2255
TABLE I Preparation of 3a–c Using Microwave Irradiation under
Solvent-Free Conditions
Starting
phosphite
Molar ratio of
(phosphite/chloral) Catalyst
Reaction time Conversion
∗
(R)
(min)
(%)
∗
∗
1
1
1
1
1
1
1
1
1
a
a
a
a
a
b
c
Methyl
Methyl
Methyl
Methyl
Methyl
Ethyl
Isopropyl
Isopropyl
Isopropyl
1: 1.01
1: 1.01
1: 1.01
1: 1.01
1: 1.01
1: 1.16
1: 1.20
1: 1.40
1: 2.00
Silica gel
Alumina
Alumina
Alumina
Alumina
Alumina
Alumina
Alumina
Alumina
1.5
3a (60)
3a (70)
3a (74)
3a (71)
3a (67)
3b (76)
3c (65)
3c (82.5)
3c (93)
3 (240)
6 (240)
9 (240)
12 (240)
4 (300)
3 (420)
7
c
c
8
∗
Based on the 31P NMR of crude reaction mixture.
∗∗
450 W.
organophosphorus compounds and the present data, the conformation
2
of this compound has been assigned. The observed JP−H = 11.5 Hz
in trichlorfon 3a suggests that the preferred conformation is anti (a) in
◦
which the hydrogen group is anti to phosphoryl group (θ = 180 ) but the
◦
coupling constant of the alternative conformation (b) (θ = 60 ) is around
1
6
2
4 Hz. Existence of hydrogen bonding between hydrogen and the oxy-
1
6
gen of the phosphoryl group has been reported in the literature. The
proton of the OH group appears at 5.48 ppm as a broad peak.
Further evidence for determination the structure of the products
were obtained from 13C NMR analysis. In the C NMR, the CHOH
13
1
carbon appeared at 79.98 ppm as a doublet with J(PC) = 662.5 Hz.
1
This large value of J(PC) is consistant with coupling of phosphorus
with adjacent carbon.16 The most downfield shift of CCl3 carbon at 97.7,
which split with phosphorus, appears as a doublet and is in agreement
with the phosphorus attached to three electronegative chlorine atoms.
The presence of hydroxyl group was indicated by a broad absorption
−1
band at 3350 cm in the infrared spectrum.
FIGURE 1

2
256
A. Javidan and A. R. Banan
CONCLUSION
In this article a straightforward method for formation of dialkyl-(2,2,2-
trichloro-1-Hydroxyethyl) phosphonates using dialkyl hydrogen phos-
phate and chloral hydrate under solvent-free conditions using mi-
crowave irradiation has been reported. This method is superior to the
reported method from the point of view of green chemistry, yields, and
short reaction time.
EXPERIMENTAL
General
1H, 13C, and 31P NMR spectra were obtained using a Bruker 250 spec-
trometer using CDCl3 as solvent and TMS as internal standard or
85% H3PO4 as external standard. Melting points were determined
on a Metler 9100 electrothermal and are uncorrected. IR spectra
were recorded on a Perkin-Elmer IR-738 spectrometer. All reagents
and chemicals were obtained from Merck or Aldrich Chemical Com-
pany and were used as received unless otherwise noted. The starting
materials, 1a, 1b, and 1c, were prepared as described in the
1
7,18
literature.
A domestic microwave oven operating at 2450 MHz
was used at power 600 W for all the microwave experiments except
that.
General Procedure
Method A (Conventional)
Reactions were performed under the same conditions using an oil
9
bath at the reflux temperature as previously reported. The product
was extracted with benzen, the organic phase was dry over MgSO4,
filtered, and put away until the title compound was isolated as white
crystal.
Method B (MW)
General method. In a mortar, dialkyl hydrogen phosphite 1a–c
46 mmol) and alumina or (silica gel) was ground with a pestle, and
8 mmol of chloral hydrate was added. The mixture was transfer to a
(
4
Teflon vessel and irradiated in microwave oven for the time specified in
Table I. As this study was done only for the comparison, the products
were not isolated, and after evaporation of the solvent the resulting
mixture was analyzed by 31P NMR.

Microwave Synthesis of Trichlorfon and Derivatives
31
2257
◦
◦
1
(
3a). m.p. 75–76 C (lit. 76–78 C). P NMR (CDCl3) δ: 18.83. H NMR
3
3
(
CDCl3) δ: 3.88 (d, JP−H = 6.5 Hz, 3H, POCH3), 3.93 (d, JP−H = 6.5
2
Hz, 3H, POCH3), 5.45 (d, JP−H = 11.75, 1H, CHOH), 5.48 (s, 1H, OH).
1
2
2
3
1
2
C { H}NMR (CDCl3) δ 54.22 (d, JP−C = 27.5 Hz, POCH3), 54.80 (d,
1
JP−C = 27.5 Hz, POCH), 79.98 (d, JP−C = 665 Hz, CHOH), 97.75 (d,
−1
JP−C = 6.8 Hz, CCl). IR (KBr) cm : 3350, 3042, 2980, 2940, 1270, 1200
(
P O).
◦
◦
31
1
(
3b). m.p. 54–55 C (lit. 55–56 C). P NMR (CDCl3) δ: 16.37. H
4
NMR (CDCl3) δ: 1.38 (t, JP−H = 7.0, 6H, POCH2CH3), 4.28 (m,
4
H, POCH2CH3), 4.49 (d, J = 11.75, 1H, CHOH), 5.86 (s, 1H, OH).
1
3
3
3
C{1H}NMR (CDCl3) δ16.36 (d, JP−C = 5 Hz, POCH2CH3), 16.46 (d,
2
JP−C = 5 Hz, POCH2CH), 64.28 (d, JP−C = 27.5 Hz, POCH2CH3), 64.33
2
1
(
9
2
d, JP−C = 27.5 Hz, POCH2CH3), 78.99 (d, C(P)OH, JP−C = 657.5 Hz),
2
−1
8.04 (d, 1C, JP−C = 40 Hz, CCl). IR (KBr) cm : 3355, 3100, 3020,
980, 1280, 1230, 1205 (P O).
◦
◦
(
3c). m.p. 108–109 C (lit. 105–106 C). 31P NMR (CDCl3) δ: 14.49.
1
3
H NMR (CDCl3) δ: 1.39 (d, JH−H = 7.0, 8.1, 6H, CH(CH3)2, 1.39 (d,
3
JH−H = 7.0, 6H, CH(CH3)2, 4.39 (d, 1H, J = 11.75, CHOH), 4.86 (m,
13
1
H, CH(CH3)2), 5.49 (sb, 1H, OH). C{1H}NMR (CDCl3) δ: 23.74 (d,
3
3
JP−C = 25 Hz, CH(CH3)2), 24.34 (d, JP−C = 25 Hz, CH(CH3)), 24.44 (d,
3
2
JP−C = 25 Hz, CH(CH3)2),73.17 (d, JP−C = 30 Hz, CH(CH3)2), 73.83
2
1
(
9
2
d, JP−C = 32.5 Hz, CH(CH3)2), 80.20 (d, JP−C = 655 Hz, C(P)OH),
2
−1
8.27 (d, JP−C = 37.5 Hz, CCl3). IR (KBr film) cm : 3350, 3065, 3010,
950, 1290, 1270, 1200 (P O).
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