Synthesis and biological activities of methyl 1-(5-methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphinates

Article abstract of DOI:10.1080/10426500212244

Methyl 1-(5-methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphinates were synthesized by the condensation of O-methyl methyl 1-hydroxyalkyl phosphinates moiety with 5-methyl isoxazol-3-oxy acetyl chloride and were tested for plant growth regulatory activity and herbicidal activity. Some compounds exhibited notable plant regulatory activity and herbicidal activity.

Full text of DOI:10.1080/10426500212244

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Phosphorus, Sulfur, and Silicon and the Related
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Synthesis and Biological Activities of Methyl 1-
(5-Methyl Isoxazol-3-oxy Acetoxy) Alkyl Methyl
Phosphinates
Hongwu He a , Meiqiang Li a , Aihong Lu a & Zhaojie Liu a
a Institute of Organic Synthesis, Central China Normal University, Wuhan, Hubei, 430079, P.
R. China
Published online: 27 Oct 2010.
To cite this article: Hongwu He , Meiqiang Li , Aihong Lu & Zhaojie Liu (2002): Synthesis and Biological Activities of Methyl
1-(5-Methyl Isoxazol-3-oxy Acetoxy) Alkyl Methyl Phosphinates, Phosphorus, Sulfur, and Silicon and the Related Elements,
177:6-7, 1651-1655
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Phosphorus, Sulfur and Silicon, 2002, Vol. 177:1651–1655
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DOI: 10.1080/10426500290093126
SYNTHESIS AND BIOLOGICAL ACTIVITIES OF
METHYL 1-(5-METHYL ISOXAZOL-3-OXY ACETOXY)
ALKYL METHYL PHOSPHINATES
Hongwu He, Meiqiang Li, Aihong Lu, and Zhaojie Liu
Institute of Organic Synthesis, Central China Normal
University Wuhan, Hubei, 430079, P. R. China
(Received July 29, 2001; accepted December 25, 2001)
Methyl 1-(5-methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphi-
nates were synthesized by the condensation of O-methyl methyl
1-hydroxyalkyl phosphinates moiety with 5-methyl isoxazol-3-oxy
acetyl chloride and were tested for plant growth regulatory activity and
herbicidal activity. Some compounds exhibited notable plant regulatory
activity and herbicidal activity.
Keywords: Herbicidal activity; isoxazole-substituted phosphinates;
plant regulatory activity; synthesis
INTRODUCTION
The useful biological properties of compounds containing the isoxazole
ring have received special attention. There are several naturally oc-
curring isoxazoles with important biological activity, such as Musimol
and 4-Hydroxy isoxazole, which is a seed-germination inhibitor.1 Their
structure has been used as the basis for the design of a number of
synthetic isoxazole derivatives, which were developed as commercial
agrochemicals.2
In our previous work, it was shown that certain aryloxy acetoxy alkyl
phosphonates or phosphinates possess good herbicide activities and
plant growth regulatory activity.3,4 In order to find new phosphinates
with better pesticide activity, the isoxazole structural unit is introduced
into their molecules, so a novel series of methyl 1-(5-methyl isoxazol-3-
oxy acetoxy) alkyl methyl phosphinates were synthesized and screened
for their plant growth regulatory activity and herbicidal activity.
Address correspondence to H. He.
1651

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H. He et al.
RESULTS AND DISCUSSIONS
Synthesis of Methyl 1-(5-methyl Isoxazol-3-oxy Acetoxy)
Alkyl Methyl Phosphinates
The title compounds were synthesized by means of the multistep pro-
cedure outlined in Scheme 1.
SCHEME 1 R = Ph, p-MePh, o-ClPh, p-MeOPh, m-NO2Ph, Pr, Et, Me.
5-Methyl-isoxazol-3-oxy acetyl chloride 4 was prepared by four-step
procedure using acetyl pyruvate and hydroxylamine hydrochloride as
starting material. Hydroxylammonium chloride dissolved in sodium
hydroxide reacted with acetyl pyruvate below 0 C for 1 h keeping
pH = 10, then dealt with by ice-cooled concentrated hydrochloric acid
to give 5-methyl-3-isoxazolol in 70% yield.5 5-Methyl-isoxazol-3-oxy
acetic ester 2 prepared by the reaction of sodium 5-methyl-3-isoxazolate
with bromoacetic ester in DMF for 3 h at 0 5 C. In order to com-
plete the reaction, the mixture was left overnight at room tempera-
ture. Intermediate 2 was converted to 5-methyl-isoxazol-3-oxy acetic
acid 3 in 48% overall yield by using 5% sodium hydroxide followed by
10% hydrochloric acid. 5-Methyl-isoxazol-3-oxy acetyl chloride 4 can be

Biological Activities of Phosphinates
1653
easily obtained in 80% yield by treating the compound 3 with thionyl
chloride.
O-methyl methyl 1-hydroxy alkyl phosphinates 7 were prepared by
addition of dimethyl phosphinate 6 and several kinds of aliphatic alde-
hydes, aromatic aldehydes using triethylamine as catalyst.6 7a h were
obtained in 53 69% yields. Preparation of dimethyl phosphinate 6 was
accomplished in two-step sequence starting from phosphorus trichlo-
ride, methyl iodide, and aluminium trichloride.7 Thus, methyl 1-(5-
methyl isoxazol-3-oxy acetoxy) alkyl methyl phosphinates 8 were syn-
thesized by the condensation of 5-methyl isoxazol-3-oxy acetyl chloride
4 with O-methyl methyl 1-hydroxy alkyl phosphinates 7. The reaction
mixture of compound 7 (0.05 mol) and 4 (0.06 mol) was stirred cooled
in an ice-water bath and triethylamin added dropwise below 0 C, then
stirring at room temperature for 4 6 h to give title compounds 8a h
in 33 65% yields, and all compounds have been identified by 1H-NMR,
IR and elemental analysis.
Biological Activities
Title compounds 8a h were tested for plant growth regulatory by wheat
(Triticum aestivum L.) coleoptile and cucumber (cucumis satival L.)
cotyledon test.8 As seen from Table I, most of the compounds had stimu-
lating activity to the growth of wheat coleoptile and cucumber cotyledon
root at 10 ppm and 100 ppm. The compound 8a, 8e inhibited the growth
TABLE I Growth Regulatory Activity of 8a h
Wheat coleoptile
100 ppm (%) 10 ppm (%)
Cucumber cotyledon root
10 ppm (%)
No.
8a
8b
8c
8d
8e
8f
0.5
13.5
+3.8
+18.9
+40.5
+12.4
+12.4
+8.1
75
+12.5
+16.8
+50
+5.9
+50
+28.6
+13.5
+21.1
+14.6
100
+75.0
+87.5
+37.5
+150
8g
8h
2.7
+21.1
+14.3
IAA
ABA
16.3
+, Stimulation; , inhibition.
IAA—Indole acetic acid; ABA—abscisic acid.
The rates were determined by percentages of the averaged
lengths of wheat coleoptile or root of treated plants to those of con-
trols at 3-day growth.

1654
H. He et al.
of cucumber cotyledon root at 10 ppm, and 8b, 8c, 8h exhibited higher
stimulating activity to the growth of wheat coleoptile than IAA at 10
ppm, but their stimulating activity to the growth of cucumber cotyledon
root at 10 ppm was somewhat lower compared with that of IAA.
The herbicidal activity of compounds 8a h was also evaluated in a
set of experiments in a greenhouse. They were tested for pre-emergence
and post-emergence herbicidal activity on Triticum aestirum L. (wheat),
Digitaria sanguinalis scop (ascendent crabgrass), Echinochloa crus-
galli (barngard grass), Brassica campestris L. (rape), Cucumis satvba
L. (cucumber), Lactuca sativa L.C., V. sacramento (lettuce), and cirsium
japonicum D. C. (setose thistle).
Plastic pots were packed with sandy clay loam soil and water was
added up to 3 cm in depth. In the pre, seeds of plant were sown, a di-
luted suspension of each compound containing acetone and Tween 80
were applied into the pots at 2,250 a.i. g/ha. Fifteen days later, the
pre-emergence herbicidal activity against each weed was visually eval-
uated, and the solution of the chemicals tested was applied to the foliage
of plants grown at 2 to 3 leaves stage with a sprayer at the rate of 2,250
a.i. g/ha with a spelling volume of 1000 L/ha. Visual assessment was
conducted 15 days after treatment on a scale of values of zero (no ef-
fect) to 100 (dead). The post-emergence herbicidal activity against each
weed was evaluated. The results showed that the compounds 8a and 8e
(pre and post) displayed 100% inhibitory effect against curcumas sativa
L.; 8a and 8b had 100% (post), and 8e and 8g had 82 90% (pre) in-
hibitory effect against cirsium juponicum D. C.; 8b also displayed 100%
post inhibitory effect against Digitaria sanguinalis scop. and 8a dis-
played 100% (pre and post) inhibitory effect against Lactuca sativa L.C.,
V. sacramento.
ACKNOWLEDGMENTS
This project was supported by National Natural Science Foundation of
China.
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Biological Activities of Phosphinates
1655
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