CA1119178A - Mono- and di- thiophosphate esters containing an isoxazolinone ring - Google Patents

Abstract

ABSTRACT OF THE DISCLOSURE
Compounds are provided of the formula II
(II) wherein R1 represents a hydrogen atom, a lower alkyl group or a halogen atom; R2 represents a hydrogen atom, a lower alkyl group or a phenyl group; R3 represents a hydrogen atom, a lower alkyl group or a phenyl group; Y represents a halogen atom;
and n is 1 or 2. These compounds are intermediates in the preparation of mono- and di-thiophosphates which have valuable insecticidal and acaricidal properties.

Description

$~.191~8 .

The present invention provides in-ter-mediates in the preparal~ion of a novel series of mono- or di- thioL~hosphate esters containing an isoxazolinone system, ~hich have valuable insectici dal ~nd acaricidal prope rties:
This application is a divisional application of copending appl; cation No.
305,100 fil~d June 9, 1978.

~nsects and arachnids ca- se considerable damage to plants, both agricultural and domestic, can be a serious danger to health or, at best, are a considerable nuisallce. Accordingly, considerable sums are spent on their destruction. Although many insecticides and acaricides are available, many of them have to be used ~vith considerable care because they endanger the health of humans or other anirnals or because of their phytotoxicity ~loreover, because of their short life cycles, insects and arachnids can deve~op im~ lity to many of the commonly used insecticides and acaricides and, accordingly, the~re is always a continlling need for new compollllds exllibitillg insecticidal and/or acaricidal properties.

' ~
' .

_~ ~119~78 I n s ~ i d ~o~ ~f ~ g ~ t; o~ )^e (~ :L-e di sclosed a c] ass of mono- and di-t:hi.opho.s-phate esters having insecticidal and/or acaricidal and/or arachnicidal properties.
The compounds of the inventionof the copending application have the formula (I ):

R~ X
R2~ Ct~R3~n-5 - P < oRl in which:
:R represents a hydrogen atom, a lower alkyl group or a halogen atom;
R represents a hydrogen atom, a lower alkyl group or a phenyl group;

R represents a hydrogen atom, a lower alkyl group or a phenyl group;
R represents a lower ~ yl group;
X represents an o}~ygen atom or a sulphur atom;
and n rcpreserlts 1 or 2 and, when n rcpresellts 2, the groups R3can be the sarne or different.

.

l ~11917 !3 The invention of the copending application also - provides an insecticidal/acaricidal/arachnicidal composition which cont~ins at least one compound of formula (I) as the active ingredient.

5 In the above, the term "lower alkyl" means -;
an alkyl group ha~ing from 1 to 4 carbon atoms, In the compounds of formula (I) ~hen R represents a lower alkyl group, it may be, for example, a methyl, ethyl, n-propyl, isopropyl or n-butyl group. ~Vhen R represents a halogen atom, it may be a chlorine, bromine, iodine or fluorine atom, When R J R and R, which may be the same or different, are lower alkyl groups, they may be, for exampleJ methyl, ethyl, n-propyl, isopropyl or n-butyl 1 5 groups, .

~ preferred class o compounds of formula (I) are those in wllich: R represellts a hydrogen atom, a methyl g~roup or a halogen atom; R represents a hydrogen atom, 1~91~8 a lower alkylgroup or a phcnyl group; R represents a hydrogen atom or a rncthyl grollp; R represents a lower alkyl group; X represents a slllphur atom and n is 1 The fol]owing is a non-]imiting list conlailling examples of compoullds of formula (I) rlle numbers appended to the compounds in this list ~Yill be used to identify them in the following Examples.

1, O,O-diethyl S-(5-methyl-3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithioate.

2 O O-diethyl S-(5-methyl-3-oxo-4-isoxazolin-2-. ylmethyl) phosphorothioate.

3 O O-diethyl S-(4-chloro-5-methyl-3-oxo-4-isox-azolin-2-ylmethyl) phosphorodithioate.

_

4 O O-diethyl S-(4-chloro-5-lilethyl-3-oxo-4-isox-azolin-2-ylmethyl) phosphorothioate.

5. OjO-diethyl S-(4-chloro-3-oxo-5-pllenyl-4-isox-azolin-2-ylmetllyl) phosp}loroclithioate.

6, O, O-d;et]lyl S- (3-oxo-S-pllellyl- ~ -isoxazolin-2-ylmethyl) phosphorodit11ioate.

7. 0, O-dimcthyl _-(5-metllyl-3-oxo-4-isox~zolin-2-ylmethyl) pllospllo3 o~litlli oate, . 8. 0, O--dietllyl S-(3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithi oate.

9 . O, O- di ethyl S- [2 - ( 5 - m ethyl- 3 - oxo- 4 -i s oxa7, olin-2-yl)ethyl] phospllorodithioate.

10. O, O-diethyl S- [1-(5-methyl-3-oxo-4-isoxazolin~
2-yl)ethyl] phosphorodithioate.

ll . O, O-dimcthyl S-[ 1-(5-methyl-3-oxo-4-isoxazolin-2-yl)ethyl] phosphorodithioate.

12. O,O-dimetllyl S-[1-(5-mctllyl-3-oxo-4-isoxazo]in-2-yl)etllyl] phospho~otllioate.

~1~9178 13 . 0, 0-diethyl S~ (5-methyl-3-oxo-4-isoxa~olin-2-yl)benzyl~ pllosphorodit~iioate, 14. 0,0-dimetllyl S-~4-cllloro-5-~nethyl-3-o:xo-4-, isoxazolin-2-ylmetllyl) phosplloroditllioate, , 15 . 0, 0- di i sopropyl S- (4 - chl oro- 5 - methyl- 3- oxo- 4 -i 60xazolin- 2-ylriethyl) phosphorodithioate.

16. 0,0-dimethyl S-(4-chloro-3-oxo-5-phellyl-4-; soxazolin- 2-yln~ethyl) phosphorodithioate.

17. 0,0-di-n-propyl S-(4-chloro-3-oxo-5-phenyl-4-isoxazolin-2-ylmethyl) phosphorodithioate.
., ~

18. 0, 0-c3iisopropyl S-(4- chloro-3-oxo-5-pilenyl-4-i soxazo3in- 2 -ylrnethyl) phospllol odithioat e, 19 . 0, 0-din~ethyl S-(3-oxo-5-phellyl-4-i~oxazolin-2-y31nethyl) phosphorodithio~te.

6, 20. O, O-di-n-propyl S-(3-oxo-5-pl~enyl-4-isoxazolin-2-ylmethyl) phosphorodithio.lte, 21~ O, O-dii sopropyl S- (3- oxo- 5-phenyl-4- isoxazolin-2-ylmethyl) phosphorodithioate.

22. O,O-di-n-propyl S-(5 metllyl-3-oxo-4-isoxazol~n-2-ylmethyl) phosphorodithioate, 23. O, O-diisopropyl S-(5-methyl-3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithioate.

24. O,O-di-n-propyl S-(4-chloro-5-1nethyl-3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithioate.

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25. O,O-diethyl S-(4-bromo-5-methyl-3-oxo-4-isox- :
azolin-2-ylmethyl) phosphorodithioate.

26 . O, O- diisopropyl S-~-bromo- 5- methyl- 3- oxo-4-if;oxazo]in-2-ylmethyl) phosplloroditllioate, 2 7 . O, O - di m ethyl S - (4 - br om o- 5 - m ethyl - 3 - oxo - 4 -isoxazolin-2-ylmethyl) phosphorodithioate.

17~

2 8 . O, O- di ethyl S - ( 3 - oxo - 5 - n - propyl - 4 - i s oxaz olin -2-ylmethyl) phosphorodithioate.

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2 9 O, O- di ethyl S- (4, 5 - dimethyl- 3- oxo-4 - i soxazolin-~-y]met.}lyl) phosphorodithioate, .
3 O, O - dii s opr opyl S - (4, 5 - di m ethyl - 3 - oxo - 4 - i s ox-azolin-2-ylnnethyl) phosphorodithioate.

31. O, O- diethyl S- ~- (4- chloro- 5 - methyl- 3- oxo- 4 -isoxazolin- 2-yl)benzyl] phosphorothioate.

32 . O, O-diethyl S - [~-(3-oxo-5-phenyl-4-iso};azolin-. 2-yl)benzyl] phosphorodit]lioate.
~ ,:
33. O,O-diethyl S-(4-isopropyl-3-oxo-5-phenyl-4-isoxazolin-2-ylmethyl) phosphorodithioate, 34 . O, O- di -n -propyl S- (4 -i sopropyl- 3- oxo- 5 -phenyl-~-i soxazolin~ 2 -ylmethyl) phospllorodithioate .

The novel compounds of formula (I) may be prepared by reacting an isoxazolinolle derivative of formula (II):

. .

.

r--11:191.78 :

~r~ (Il) R2 n ~ ( c H R3~Y
.

t;
(in which Y represents a }lalogen atom, and R, R, R and n are as defined above) ~lrith a salt of a phosphate ester of general lormula (III) . ~ -M - S - P<

,. . .

. tin ~vhich :R and X are as defined above, and M
represents an,alkali metal atom, an ammonium ion or an organic ammonium ion).

-- The reaction is preferably carried out by dissolving the iso2;azolinone derivative of formula (II) in a solvent and then adding the salt (III) as such or dissolving or disper sing it in a solvent and adding the solution or dispersion, and finally stirring the resulting mi~;ture at the rcaction temperatllre. There is no particu1ar lirnitation upon the nature oi the solvent cmp10yed, provided that it has no adverse effect upon :.

1~19~78 t]-le rcaction. Suitable solvents include:
arolnatic hydrocarbons, sucll as ben7elle; chlorinated alip]~atic hydroc:arbons, such as met]lylelle ch]oride;
and ketones, SUC]l as met]lyl ethyl ketone or acetone.
A s;ngle :;uch sc~lvent or a mixture of two or more thereof may be emp]oyed, Of these solvents, we prefer to use acetone, The order of addition of the reactants is in no ~t~ay critical and, if desired, instead of adding the salt (III) to the isoxazolinone derivative (lI),the iso~;azolinone derivative ~ may be added to the salt (III).

There is also no particular limitation on the 1~eaction temperature and, for this reason, it is preferable to use ambient temperature, although temperatu1;es above or belo~t~ this may be employed, if desired.

After completion of the reaction, the desired -product may be separated from the reaction mixture by collventional means, For c~;ample, if the reaction is performed in a ~ater-miscible solvent, ~0 such as acetone, the solvent is distilled off ~ater and a ~ater-immiscible solvent (such as bcllzcne, diethyl ether or rllet]lylelle chloride) are ad(led to the residue; the 1119:~7~3 aqueo~ls phase is separated; the organic pllase is ~vashed, e, g, with, in turn, an aclueous solution of an allcali metal carbonate and water; the solulion is dried; and finally - the solvent is distilled off, affording lhe desired compound, This cornpound may, If necessary, be further purified using any appropriate converltional technique, SUCIl as chrom atography, , The isoxazolinone derivati~/es~!~ormula (II) used as inlermediates in the synthesis of ihe compounds o formula (I) are also novel compounds and form the present invention. The preparalion of these novel intermediates is given below.

Compounds of formula (II) in which n is i may be prepared by reacting a compound of formula (IV): -.__ R \r ~OH (lV) ~ 2~ ,IN

- (in which ~l and ~2 are as defined above) wilh a compound of formula (V):

R - CHO (V) ~1~9178 .
(in w]lich I~ is as defined above~ or a polymer thereof and with a compound of formula (VI):

2 ( V I ) . .
(in which Y is as defined above and the two groups Y
may be the same or different), The aldehydc of formula (V) or its polymer employed will depend upon the compound of formula (II) ~ ;`
which it is desired to produce, Examples of such aldehydes and their polymers include: formaldehyde, trioxymethylene, paraformaldehyde, acetaldehyde, paraldehyde and benzaldehyde. Examples of suitable thionyl halides of formula (VI) include thionyl chloride, thionyl bromide, thionyl fluoride and thiol~yl bromochloride, of which we preIer thionyl chloride and thionyl brcmide.
, ~ lthough we do not wish to be limited on any theory, it is be~ie~cd that, in the above reaction, the iso~azole of formula (IV) reacts first with tlle aldchyde of formula (V) to give a compound of formula (VII):

Q

.

R~ O .
~ (VII) 2--o~N~ C t~ R3 OH
(;n which R, R and R are as defined aboYe), AIler tllis, compound (VII) reacts with the thionyl halide of formula (VI) to ~ive the des;red compowld of formula (II) - Thus, one way of carrying out the reaction to prepare the inter~nediate of formula (II) is to react the compound of forn~ula (IV) first with the aldehyde of formula (V), o its polymer, preferably in equimolar amounts or ~vith the aldcllyde in a slight excess. This gives tlle compound of formula (VII), which, with or without intermediate isolation, is then reacted with the thionyl halide of formula (VI), the thionyl halide preferably being e3llployed in an amount grealer than equil3l01ar, tllus affording the dcsired compound of formula (II) l~]though the intermediate compound of formula (VII) can bc isolated, if dcsired, it is generally somcwhat unstable alld we tlleIcfore prefer that it sho~lld not be isolated, l~n altelllative way of prcparing the intclmcdiate 13, .

isoxazolinone dcrivatives of formula (~I) is to react the isoxazole of formu]a (IV) with a mixture of the aldel yde (V)or polymer allcl the thionyl halide (Vl).~ The aldehyde is prefei ~bly employed in an equimolar arnoullt or in a slight exccss and the thionyl halide is preferably employed in an amount in excess of equimolar.
.

It will, therefore, be ullderstood that the order of addition of compounds (IV), (V), and (VI) is not critical in the preparation of the compounds of formula (II).
The reaction is preferably carried out in the presence of an inert organic solvent; where a solvent is employed, its nature is not critical, provided that it has no adverse effect upon the reaction. E~iamples of suitable solvents include: halogenated hydrocarboi~s, such as methylene chloride and chloroform; and aromatic hydrocarbons, such as benzene, toluene and xy]ene, The reaction may be carried out over a wide range of temperatures, but is preferably carried out at a temperature from 0 C to the reflux tempcrature of the solvent employed '~ 20 and is more preferably carried out at a temperature within t]lC range from lû C to 80 C, The reaction is complcte when cvolution of hydrogen halide and sulpllur dio~ide gas ccases, . .

1~917~3 .
After completion of the reaction, the compound of formula (II) can be obtained by evaporating the solvent and the e~ccss thionyl ~alide (if ,Illy) from the rcac:~ioll mixture.
If necessary, lhe compound may be purificd by convcntional means, e, g, by recrystallization or by column chro1nato-graphy, wl1icE1 can be perfor1ned under conditions known ~r se.

Colnpounds of formula (II) in ~ hich n is 2, may be obtained by reacting a compound of formula (IV), defined above, with a compound of for1nula (VIII):

y ~ C H ~Y ( VIII ) . , _ 2 (in which Y is as defined above), The simplest means of carrying out this reaction is merely to heat togetller a mixture of the two rcactants under reflux, We have found that the compolillds of formula (I) exhibit insecticidal and/or acaricidal activity against a widc variety of insect and arachnid pests, including agric:ultural insects and rnites, such as rice stem borers, plant~oE)pers, rice lcafhoppers, scale insects, leaf rollers, ~' lniteS and ;3phids, as well as don~cstic insects, such as ~ . ~ . , 1 1119~L78 , l , .
~ flies, mosquitoes and cockroaches, ~

In order to control effeclively harmful insects, arachnids and acarids, the compounds of formula (I) may be formulated with carricrs and diluents well-hliown in this ~rt, particulclrly will~ agricultulally-acceptable carriers and diluents, by convelltional tec]~niques, The resulting col-npositions may be in various forms, ~.
including liquids, dusts, granules and wettable powders.
s I,iquid formulations may be prepared by dissolving the active compound of formula (I) in an appropriate liquid . and, if desired, adding conventional adjuvants, such as e~nulsifying or dispersing agents, Suitable :
;~ solvents include alcohols, such as methanol and ethanol;
ketones, such as acetone; aromatic hydrocarbons, such as benzeneandxylene andotherconventionalsolvents, such :
:~ as~solvent naphtha, Exan~ples of adjuvants include condensation products of alkylene glycols with phenols or with organic acids, alkyl aryl sulphonatcs and polyoxyethylene ether or cster derivativcs of alcohols or acids, Dusts and granules may be prepared by mixing the ;!
16, . .. , .
.
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~119178 active con~pol~nd of formula (I~ wilh an i~ ert so~id carrier, Suilab1e solid carriers include talc,pyropllyl]ite, clay, 1~enlc)nite, diatomaceous eartll and l~aolin, Wettab]e powders may be prepared l~y mixing the active comp()und ~ilh one or more solid carriers (such as those exelllplificd above for dusts and granules) and with one or more suitable dispersing agents, such as alkyl-1-Jcn%ellesu]phol1ales, polyvinyl alcohols, lignosulphonates and polyo~;yalky]ene glycol ethers and esters, Tl-e concentration of the acti~e compo~lnd of formu]a (I) in the cornposition may vary over a ~vide range, although it will normally be from 0, ~ to 95 % by weight and more preferab]y is from 0, 5 to '70 % by weight, Howcver, lhe concentration is not critical and may be ch.lnged at will depending upon such factors as the form of thc composition, the particular active compoul1d chosen al-ld its toxicity, the spccies of insect, aracllnid or acarid to bc attackcd and thc mcthod of application.

'rhe insecticidal and acaricidal comyositions of ~,0 the invention oL the copending aypllcation may also ;nclude other known insecticidal agents, such as O,O-dimcthyl 0-~ methyl-4-nitrO~henyl) 17, ,q~ 4~
~9~, 8 phos~ ol olhioate, O, O-diethyl 0-(2-isopropyl-~-metllyl-6-py~ ;d;nyl) phospllol-ot]l;oate or O,O-dictllyl S-2-(etllyl-thio)ctl-lyl phospllorodithioale; or fullgicidal agelltS, such as kasugaInycin, ZillC etlly]enebis(litllioca1l:)amate or melhyl ben7,imida~01-2 -carbamate.
Thus, the invention of the copendin~l a tion also provides an in~:t?cJ:icida1 . and/or acaricidal composition con-lprisillg at least one compound of formu]a (I) in admixture wilh a carrier or diluent, -The invention of the copending application also provides a method of treating growing crops to control insects, arachnids and acarids, which comprises applying an effective a nount of at least one compound of formula (I) to the crops or to the soil in which they are growing, The compound or compcunds is normally applied at a concentration or aggrcgate concelltIation of at least 5 ppm for liquid preparations (i, e, liquid compositions and diluted ~Yettable ~owders) and in an amount of from 7 to 150 g of active corn~ol-nd or compoull(ls (I) per 10 arcs for solid preparatiolls sucll as dusts and granules.

The invention is fuItller illustlated 'oy the follo~ving 18, . .

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:"' ,. :

~19~78 mples, of whicll ~3xamples 1 to 7 illustrate the preparalion of the compounds of the invention of the copending application and Examples 8 to 15 illustrate their use in the control of insects and other pests.

~3X~NI PLE
O,O-di-n-propyl S-(5-methyl-3-oxo-4-isoxazolin-2-yl-methyl~ pllosphorodithioate -_ _ (a) To a mixture of 4. 95 g of 3-hydroxy- .
5-melllylisoxazole, 1, 7 g of paraformaldehyde and 20 ml of benzene were added 5 ml of thionyl chloride, and the mixture was then refl~xed for 30 minutes. After - completion of the reaction, the solvent and excess thionyl chloride were distilled off and diisopropyl ether was added to the brown oily residue to form crystals, J~ecrystallization of these crystals from diisopropyl ether gave 6, 35 g (86. 5 % of theory) of 2-clllorometllyl-5-mcthyl--isoxa~olin- 3 - one, ' (b) To a solulion of 1. 48 g of the 2-chloro-rn(?thyl-5-metllyl-4-isoxazolin-3-olle tlllls obtained in 30 ml ' ~ ' -~1~9~78 of acetone ~ere added 2 52 g of crystalline potassium O O~ -n-propyl dithiopllosphate and the resulting mixture was then stirred for 1 hollr at ~n~bient tclnperature rhe ncetone ~as then evaporaled off and the residue was purified by column chrolnatography through silica gel eluted with a 20: 1 by volume mixture of bcnzene and acetone Tllere were ol~tained 2 39 g (73. 5 % ~-of theory? of O O-di-n-propyl S~5-methyl-3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithioate in the form of a pale yellow oil n D = 1 53~4 Eleme]ltal analysis:
Calculat~d for CllH20~o4ps2: :
~ 4 30 %; P 9 52 ~o; S 19. 71 %.
Found: N 4.17 %; P 9 11 %; S, 20 17 %.

~~ EXAM ~I.E 2 O O-diethyl S-[1-(5-methyl-3-oxo-4-isox~zolin-2-yl)ethyl~
'~ phos phOI'OditlliOate __, ___ _ (a) A n~ixture of 2. 97 g of 3-hydroxy-5-mc~llylisoxazole 1.32g of ~araldehyde 3 ml of thionyl chloride alld 20 ml of benzcne ~as stirred for 1 hour at , ' .

.. , :

~l~lgl78 40 - 50 C, On evapor~ltillg off the solvent and cxcess thionyl chloride, there were obtained 4, 97 g of crude, crystalline 2-(l-chloroctllyl)-5-meth ,rl-4-iso~a-~olin-3-one.

(b) 0, 81 g of lhe crude crystals obtained above were dissolved in ~5 ml of acelone, and then 1 12 g of potassium 0, O-d-ethyl dithiophosphate were added to the :"
solution, The rnixture was stirred for 5 rninutes, and tllen lhe acetone was distilled off, leaving a residue. .10 ml of ben:~ene were addcd to this residue and lhe mixture was then fillered and the rcmaining crystals were washed five times, each with 2 ml of benY,ene, The filtrate and the washings were co~,hined and then concentrated, by evaporation under reduced pressure, to a volume of a.bout 5 ml, This concentrated solution was purified by column chron~atograph~,~
through silica gel eluted with a 20: 1 by volume mi~iture of benY,ene and accto]le, There was obtailled 1, 03 g (~6. 2 ~0 of thcory~ of 0, O- diethyl S-[1-(5-methyl-3-oxo-4-isoxa~olin-2-yl)etllyl~ phosplloroditllioate, in llle form of a ycllow oilJ n 5D = ~ 5309 . ~31cmcntal allal.ysis:
,, , , 21.

~119178 c~ cu]rlted for CloJ~l8N4 2 N, 4, 50~; P, 9, 95%; S, 20 60%.
'~ Found: N, 4, 66 '~; P, 9 17 %; S, 20, 57 %.., . . ~ ~, O, O-diethyl S - (4 - chloro - 5 -m et}lyl- 3 - oxo-4 -;soxa~.olin- 2 -_ _ __ _ __ yln~ethyl) phosphoroditllioate (a) To a mixture of lO0. 2 g of 4-chloro-3-hydroxy-5-melhylisoxazole, 24 g of paraformaldehyde and 400 ml of benzene were added 75 ml of thionyl chloride, .0 whilst stirring and cooling to 10 C. The mixture was then stirred for a îurther 30 minutes at 10 -15 C, after which it was heated gradually over about l hour to reflux temperature, The solvent and excess thionyl chloride were evaporated off under reduced pressure, giving 137, 5 g of crude, crystalline 4-chloro-2-chloromcthyl-5 -n~ethyl-4 -isoxazolin-3-one (b) 1~ mixture of 0. 91 g of thcse crude crystals, ~, 20 g of potassium O, O-dictllyl dithiophosphate al-d 15 ml of acetone was stirred for 1 hour at aml~ient ternpcrature, Tlle solvcnt ~as then 22, .

distillccl off and 5 ml of benzclle were added to the rcsiclue, 'rhc .s~olution was fillered and the crystalline potassium chlorjde filtered vff was washed five times, each with 2 ml of ben7,ene, rrllc filtrate and the washings ~ere cornl~rlled aIld concentrated, by evaporalion under redllced pressure, to about 5 ml. This concentrated solution was purified by column chromatograplly through silica gel eluted ~ith a 10: 1 by volume mixture of bcn~,c3le and acetone, There ~vere obiained 1. 40 g (~34. 3 % of theory) of O, O-dietllyl S-(4-chloro-5-methyl-3-oxo-4-isoxazolin-2-ylmethyl) phosphorodithioate in the form of a pale yel]ow oil, n D = ~ 5457 Elemelltal analysis: -Calculated f r Cg 15 4 2 N, 4, 22 %; Cll 10. (~9 %; p, 9, 34 %;
S, 1 9, 33 'lo .
~~ Found: N, 4. 14 %; Cl, lO, 75 %; P, 9, 03 ~0;
,S, 20,29%, EXAI\~IPT,E 4 O,O=djclhyl S-(4-c}l1Ol-o-5-llletllyl-3-oxo-4-isoxazolin 2-yl-~1~ ctl~yl) pho~-;pllol oclitllioate . _ _ _ . _ ., .. ~ ., . ., ._ _ ._ _ _ _ _ _ . _ __ ___ ._ . _ .' 23~

., .

!

(a) To a rnixture, cooled to 10 C, of 13, 4 g of 4-chloro-3-hydroxy-5-ll~ethyliso~azole, 3. 3 g of paraformal~ehyde and ~00 ml oI benzcne wcre added, with stirring, 10 ml of lhionyl e]lloride; tl~e ~ ;turc ~vas thell gradually heated over about 1 hour to reach reflux.
;; The solvent and excess tl~ionyl chlor;de were then distilled off and the residue was dissolved in 50 ml of acetone to give a solution of crude 4-ch]oro-2-chloromethyl-5-methyl-4-isoxazolin-3-one, ., (b) Meanwhi~e, an acetone solution of ',5 crude potassium O, O-diethyl dithiophospllate was prepared by dissolving 20 g of O~ O-diethyl dithiophosphate (purity about 90 %) in 100 ml of acetone and then a(lding, with - , stirring, 8 g of anhydrous potassium carbonate to the solution in small portions at arnbient temperature, . ~

-- (c) To the solution obtained in step (b) above was added dropwise the isoxazolinone solution ol~t~ined in step (a) al)ove, with stirring, over a period of 5 minutes at ambicnt temperature, The :.
mixture was then stirred for a further 30 millutes, also at ambient temperature, AIter distillillg off '! ' ,, thc solvent, ~00 Inl of benzelle and 25 ml of water were 24, , . . .
.
. ~ , ~1917~

addcd to t}le rccsidue and tl~e benzelle p]-lase was washed,in turn, ~ith 25 ml of a 5 % ~ aqueous sodiurn bicarbonate solulion and twice ~ith lO0 ml OI a saturaled aqueous so~ium chloride solution, The ben~.ene soll~tion was tllen (~ried over al]ll~ ro~s .sodium sulpllate and the solvent ~,~as distilled off. . The r esidue was then puriiied as described in step (b) of Example 3, afîording ,28, 5 g (85, 8 '10 of theory) of O, O-diethyl S-(4-chloro-5-melhyl-3-oxo-4-isoxa~olin-2-ylmetllyl) phosp11orodi~1lioate, in lhe form of a yellow oil, n OD = l. 5457, :Elcmenlal analysis:
Calculated for CgH15ClNO4PS2:
'' Cl, ~0. 69 %; N, 4, 22 %; P, 9, 34%;
~, l9, 33%, l~oulld: Cl, 10, 75 ~0; N, 4, 14 %; P, 9. 03%;
S, 20, 29 %, ,;

FXAMl'~ E 5 O, O- dielhyl S ~ ( 5 -m cthyl - 3 - oxo- 4 - is o~az olin -2 -yl)bcllzyl]
" _ _ _ _ __ _ ._ _ _____ __ _ _ . __ __ _, _ _ _ G, phosphoroclitllioale "
'20 To a SO]utiOIl of l, 12 g of 2-(~Y-clllol oben%yl)-5-,,~ .
25, , `:

met]lyl~4-isoxazolin-3-one in :15 ml of acetolle were added 1, 12 g of potassium O, O-dielllyl dithiophosphate, and the mi~;ture was then shal;en for sevel al minutes, After lhis, 20 ml of benzelle ~ere added to the reaction mixture and then most of the acetone was distilled off.
After filtering the solution, the solvcnt was distilled from the fillrate and the remailling yellowish-brown oil ~l!as purified by column chromatography thl ough silica gel eluted ~ith a 20: 1 by volume mixture of benzene and 10 ac:etone There were obt~ained 1 16 g (62. 0 %
of lheory~ of ~), O-dielhyl S-~-(5-metllyl-3-oxo-4-isoxazolin-2-yl)benzyl] phosphorodithioate, in the form of a pale yellow o11, n D = 1, 5697, Elemental analysis: -lS Calculated for C15 H20NO4PS2:
- N, 3. 75 %; P, 8. 29 %; S, 17. 17 %, - Found: N, 3. 77 %; P, 7. 54 %; S, 17. 51%.

,, .
, _AM PLE 6 O,O-dietllyl S-[2-(5-metllyl-3-o~io-4-isoxazolin-2-yl)etllyl]
phosphorodithioate _ .

.. . .
26, .
,. . .
;' ' '' ' ' ,.

~119178 (a) A mixturc of 10 g of 3-hy(lroxy-5-n-~ethylisoxazole and 56 g of 1~2-diblomoethane ~as refluxed for G hours, After cooling., the reaction mixture was subjectcd to co:lun)n chromatogra~ y lhrough silica gel elllted ~vith a 3: ~ by volume rni.xture of bcnzene alld acetone, A 1e]1Ow licluid separated, alld this was cr~stallized with n-hexane, affording 2-f2-bromoethyl~-5-methvl-3-oxo-4-isoxazoline, rnelting at 39 - 40C.

(b) To a suspension of 1 g of the compound obtained in step (a) above in 20 ml of acetone were added 1.~35 g of potassium ;~
,J . O, O-diethyl dithiophosphate, and the mixlure ~as stirred ,~', at ambient temperature and then heated for 7. 5 hours at 50 C, After distilling off the acetone, diethyl cther was added to the residue and the resulting solution was i ~ashed, in turn, with a saturaled aqueous solution of sodium s~ bicalbonate and with water, and finally dried. The diethyl ether was evaporated off and the residue was purified I:y colllmn chromatography through silica gel eluted with a ;. 20 20: 1 by volume mixture of benzclle and acetone.
i~ There w ere obtained 1, 46 g (94. 2 % of theory) of O, O-di-. cthyl S-L2-(5-1nethyl-3-oxo-4-isox.Lzolin-2-yl)ethyl] phos-pllorodit}lioate, n ~' D = ~. 53~2, ,.................................... . . .
,. ~ ~ , .

: .

~9178 EX~MPI,E 7 O, O-diethyl S-(5-1nethyl-3-oxo- 4 -isoxazo]in-2-yl~netllyl) phosphol-otllic)al.e To a soll~tion of l, 48 g of 2-chloromethyl-5-methyl-~-isoxazolin-3-one in 20 n1l of acetone wele addcd l, 92 g of sodiull1 O, O-diethyl thiophosphate, and then tlle mixture was stirred for l hour at ambient temperature, The solvent was then distilled from the reaction mixture and 50 ml of methylel1e chloride and 30 ml of water were added to the residue, The metllylene chloride phase was separated and dried over anhydrous sodium sulphate, The solvent was then evaporated off and the residue was purified by column chro~natography through silica gel eluted with a lO: 1 by volume mixture of benzene and acetone, There were obtained l, 84 g (65. 5 % oi theory) of O, O-diethyl S-(5-methyl-3-oxo-4-isoxazolin-2-ylmetl-1yl) pllosphorothioate, in the form of a pale yellow oil, n D = l. 5029, ' .

li`ollow ing substantially the saln e proc edul es as ~0 are described in Examples 1 to 7, the following compourlds were synthcsi~,ed:
'' 28, :1~19178 O, O-diethyl S-(5-meUlyl-3-oxo-4-isox azolin- 2-y]n~ctllyl) phosplloro(litl-lioate n D = 1, 5~50, O,O-dietllyl S--(4-ch]oro-3-oxo-5--phenyl-~-iso~:~zolin-2-ylmethyl) phosphorodithioate n D = 1. 5984, O, O -diethyl S -( 3 - oxo- 5 - phenyl - 4 - is ox a% olin - 2 -~]m cthyl) pi~osphoroditllioate: n D = l. 5914; mp 38 - 39 C, O, O -dim ethyl S - ( 5 -m ethyl - 3 - oxo - 4 - is o;~az olin - 2 - ylm ethyl) phosphorodilllioate: n D = 1 5546, O, O -cliethyl S - ( 3 - ox obenzis oxazolin - 2 -ylrr. ethyl) ph osphoro-dilhioate: n 3D = 1, 5772, ;

O, O-dimethyl S-(3-oxobenzisoxazolin-2-y]me'hyl) phosphoro-dithioate: n 5D = 1, 598~, O, O-din-lethyl S-(4-chloro-5-methyl-3-oxo-4-isoxazolin-2-y]methyl) phosplloroditllio~te: n D - 1, 5567, O, O-diisopropyl S -(4-chloro-5-methyl-3-oxo-4-isoxazolin-~0 2-ylmetllyl) phosplloroditllioate: n D = 1, 5292, O, O-di]nethyl S-(4-chloro-3-oxo-5-phcnyl-4-isoxa%olin-2-. _ _ ylmethyl) phosplloroditllioate: mp 106 - ~0'7 C, O,O-di-n-propyl S-(4-chloro-3-oxo-5-phellyl-4-isoxazolin-2-ylmetllyl) phosphoroclitllioate: n D = l. 5838, , 29, 7~3 O, O-d;isopropyl S-(4-chloro-3-oxo-5-pllcllyl-4-isoY.azolin-2-ylrl~etllyl) pl~osphoroditllioate: n D = 1, 5812, 0, 0-di~nethyl S-(3-oxo-5-phenyl-4-isoxazolin-2-ylmctllyl) phospllc)rodit]3ioate: n D = 1. ~138; n~p 44 - 45 C.
0, 0-di--n-pl-opyl S--(3-oxo-5-phenyl-4-isoxazolin-2-yllrJetllyl) phospllol odilhioate: n 2D = 1~ 5802.
O, 0-diisopropyl S-(3-oxo-5-phenyl-4-isoxazolin-2-y]methyl) phosphorodithioate: n D = 1, 5760, 0, 0-diisopropyl S-(5-nnethyl-3-oxo-4 -isoxazolin-2-ylrllethyl) phosphorodithioate: n D = 1, 5266.
0, 0-di-n- propyl S-(4 -chloro-5-metllyl-3-oxo-4-isoxazolin-2-yl-methyl) phosp}lorodit31ioate: n D = 1, 5336, 0, 0 -diethyl S - (4 -brom o - 5 -rn ethyl - 3 - ox o- 4 - is oxaz olin-2 -yl-methyl) phosphorodithioate: n D = ~ 5562, 0, 0-diisopropyl S~4-bromo-5-methyl-3-oxo-4-isoxazolin-2-ylrnethyl) phosphorodithioate: n lD = 1, 5398, 0, 0-dim ethyl S - (4 -brom o - 5 -rll ethyl- 3 - oxo-4 - is oxaz olin-2 -ylNIethyl) phosplloroclitllioate: n D = 1. 5757, O,O-dietllyl S-(3-oxo-5-n-propyl-4-isoxazolin-2-ylll~etllyl) ?,0 pllospllol oclitllioate: n D = 1, 5311, 0, 0-diethyl S-(4, 5-dimetllyl-3-oxo-4-isoxazolin-2-ylmeihvl) phospilorodit}lioate: n OD = 1, 5382, 0, 0-diisopropyl S-(4, 5-dimethyl-3-oxo-4-isoxazolin-2-yl-nctlly]) pllosp}loroditllioate: n D = 1, 5244, 30, 9~78 O,O-die1hyl S-[~-(3-oxo-5-phcnyl-4-isoxazolin-2-yl)l~en~yl]
pl~osp]lorodithioate: mp 99 - ïoo C.
0,0-c3ictllyl S-(4-isopropyl-3-oxo-5-phenyl-4-isox~Lzolin-2-ylmethyl~ phosp]lorodithioate: n D = 1 5~89 O,O-di-n-propyl S-(4-isopropyl-3-oxo-5-pl~enyl-4-iso:;azolin-2-ylmetllyl) phosphoroditllioale: n22D = 1. 5613, ~ :
O,O-diethyl S-(4-chloro-5-me11lyl-3-o~o-4-iso.~;aæolin-2-yl-melhyl) phosphorothioate: n D = 1 5089.
.
r ' ~

A~ i t ~ " ~ s ~he green peach aphid , , .

A wettable powder was prepared by holllogeneously -. . -.
mixingandpulverizing three times in a pulverizer 10 parts of each of the test compounds indicated in Table l, 4 parts of sodium dodecylbenzenesulphonate, 2 parts of polyvinyl a]collol and 84 parts of clay. The wettable powder thus preparcd was then diluted with water to the conccrltration indicated in Table 1 and then 0. 01% of Gramin (a spreader) was added, Using a sprayer, the diluted solution thus obtained was sprayed onto the lcaves of a cabbage bearing green peach aphids (Myzus pcrsicae) in an alnouJIt of 10 ml per leaf The -. : . .: .
~ : .
.: , ~19~7~3 le~lves ~ere tllen ~ ced into petri dislles and ]eft in a room rn.-lint..in~d at 25 C. l~fler 24 hollrs, tl~e perccntage mol~tality of the ~phids ~vas assessed, Tlle r esl21ts arc given in Table 1, which also gives lhe S resl~lts obtained in a control experil~ent ~7.~heIe tlle solution app]icd colllailled no active con~pound.

Table ~

Mor~ali.ty of aphids (~) Tes t Compound No. . __ . _ Concentration of act~i~,-e com~d.
0 100 ppm 50L 5 ,___ _ _ ___ _ ,1 ,., 100 100100 - :~' . 3 100 100100 7 . 100. 10083 . ~ 100 1006Q

14 . 100 1 00 32 19 100 100 ~2 29 100 100 ~7 _ _ _ _ Non e O
... ~.~ . _ _=_ _ _ ~ _~_. _ ~ _ __ 32, 1~9~7~3 :13~AMPLE_9 Activity agairlst the green pcacll apllid - A wettable powder preparcd as described in Example 8 was diluted with water to thc concentration indicated in Table 2 and then poured into 30 ml bottles. Leaves of a cabbage bearing green peach apllids were placed into the bottles througll the leafstalk, the moulhs of the bottles were plugged with cottonwool, and the bottles were then left in a room maintained at 25 C. -- After ,.....
72 hours, the percentage mortality oi the aphids was assessed.
;' The results are given in Table 2.
.

Table 2 ~ .

.. ..
Test compound No. Mor~ality of aphids (%) Concentration of active com~ound _ 5 0 ppm 2 5 1 5 100 1~ ~ 98 3 lO0 lO0 62 24 7 lO0 lO0 lO0 lO0 ~
14 lO0 lûO lO0 93 __~9 lO0 lO0 ---- 94 50 None ¦ 0 ~ . . .

33s . .

.:
: - ~

~9~7~

.
EXl~ PLE 10 .
~ctivity against the gl een rice lcafhopper A dust was prepared by homogeneously mixing and pulverizi]lg t~vice with a pulveri~er 2 parts of each in turn of the te.st compounds indicated in Table 3 and 98 parts of clay, A plastic pot having an inside diameter of 10, 5 cm and in wllich 3 rice piants of height 15 cm were pl~lnted was covered by a transparent plastic cy]inder having an inside diameter of 9, 5 cm and a height of 25 cm, The 2 10 dust prepared above was then applied to the rice plants in the pot at the ratë indicated in Table 3 and then about 15 final instar lar~ae of the green rice leafllopper (Naphotettix cincticeps, of the Shinwa strain kno~vn to be resistant both to conventional organic phosphorus and carbamate insecticides) were released into each pot, ~fter n~intailling the pots for 3 days at 25 C, the percentage mortality of the larvae was assessed, Each test ~as carried out twice, The r esults are given ~,0 in Table 3, 34, 7~

Tab]e 3 . Mortality of larvae (~) Test Compound No. 2% dust amount applied per pot 50 mg 10 m~
~ . _ . .___ ___ __ l 100 100 6 100 89.7

8 100 75.9 100 89.7 -:

23 100 95.2 24 - 100 -- 95.2 2 S ~ ~ o ~ ~ 1 O O

32 .lOO 100 100 96.0 .. ~ ._.. ~. _, .,_ _ _ _ __._ __ _ .
l~one O . ~
__ _ _ _ _ __ _ _ _ __ _ . _ 35, ~9~78 EXAMPI,E_1 1 Activily against the brown p]anthopper ___ _ _ _ ~

Follo~ing substc.nlially the sall~e proccdures as descrihed in 13~;ample 10, tlle final instar larvae of the brown p]arlthopper (N_ap rvata 11 cns) were released into pots containing rice planls clusted ~A~ith a 2 % dust containing the compounds shown in Table 4, and the percentage : n~oltality of the larvae after 3 days was assessed The results are shown in Table 4.

Table 4 Mortality of larvae (%) Test Co~pound No. 2~ dust amount applied per pot . ~0 mg lO i~g __ _ __ ___ _ l . lO0 79.3 7 . lO0 85.7 8 lO0 25.9 22 lO0 33.3 24 ~00 13.3 lO0 56.7 28 lO0 36.7 29 lO0 ~0;0 _ ___ __ _. _ ___ _ ___ _ . _ _ __ __ , __ l~one . O
., .. _ . _. ., .. _ ., . ., _ . __ __ .. . _ 36, ctivity against the tobacco cutworm Leaves of a cabbage were dipped for 30 seconds into a diluted wettable powder (prepared sul~stantially as dcscribed in E~;ample 8) llaving the concentration .shown in Table 5. Tlle leaves were then air-dried and each leaf was placed into a p]aslic icecream cup having a diameter of 8 cm, Third instar larvae of the tobacco cutworm (Spodoptera litura) were released into ~ach cup and, beginning on the next day, they were fed untreated .
fresh cabbage leaves. After 5 days, the percentage mortality of the cutworm larvae was assessed.
The tests were conducted in duplicate, using ~0 larvae in each test, The results are given in Table 5, 37.

1~9~8 .

Table 5 _ _ ~ _ ___ _Mor_ali ty of_12 rv.ae ( -~'O)_ ___ __ Test compound No. _ C nc~nt r~ ion of ~lciive_c ~ound . . _ __ _ _ _ 1_O 0_~pm__ __ 10 0_ _ l _ I

' 3 ' 50 10 ,0 ;~
7 . ' 100 55 0 8 . - 60 0 0 11 45 . 0 ~

14 75 1 l0.Ls_ . _ E~AMPLE l 3 Activity against the green peach aphid, Green peach aphids naturally breeding on cabbages planted on ~2 October in a plastic house were sprayed on 1~ January oi the next year Wit]l a diluted wettable powder containing 250 ppm of the active compounds specified in Table 6, at tlle rate of 100 ml per plant, The number of surviving aphids ~vas cowltcd 3 days and 10 days after app~ication, Two plants were used in each tcst, l'he r csults are sllown in Table 6.

38.

lllg~78 The number of aphids before sprayillg and in the control e~ peril~ ent where the spray contained no active compoulld were roullded to the nearest ten, Table 6 Test compound No. two platf surviving aphids per Before After After _ __ . __ _spray 3 days10 a2yS

. 3 1540 0 0 . 7 1500 0 25;
14 1630 0 0 .

29 _1150 _ 22 None 710 ~1010 3200 The aphids found on some of the p]ants after 10 days ~ here thcrc had becn none after 3 days are the result of the infiltration of aphids from outside the plastic house;
this indicates that, as witll otller known insecticides, repeated treatmcnt of plants is necessary for complete succ~ss.

39.

~AMPL:E~ 14 Activi~against tlle lwo-spotted spider mite __ ._ .__ __ _ _ _ _ _ _ __ _ Leaves of the cowpea (Vlgna sinensis) bearing susceptible two spotted spider mites (Tetrallych--s urticae) were dipped for 10 seconds into a diluted wettable powder prepared as described in }3xal~ple 8, and the e~cess liq~lid was allo~ed to drop off. The leaves were then placed into petri dishes and tlle percentage mortality of bearing adult feI~ale n~ites was assessed after 24 hours.
Furthermore, the :l.ife and death of eggs (i, e, the presence of hatching) was assessed after 14 days, The rcsults are given in Tables 7 and 8, Table 7 -Mortality of adult rema]e mites (~3 Test compound No. _ Concentration of active compound (ppm) ~ 1000 300 lO0 3~10 ----___ _ _ ._ __ ___ _ 100 100 lO0 66 23 3 lO0 100 lO0 7315 100 ] 00 lO0 35 7 :
20 , . 6 lO0 42 23 _ ~_ . ; .
~ . . _ __ _. __ None . 7 ' .
_ _ _ ... . _ .. _ _ _ _ _ _ . _ ~

40, 11~9178 .
Table 8 . . ~ortality c)f ~ggs (%) _ _____. _ _ T~st c~ompound No. Coi-,centrat i.on of active compd. (ppm) .
. -lO00 300 lO0 ___ __ _ _ ~ _,_ .__ __ ~_~
l lO0 lO0 45 _ - 3 _ lO0 100 33.

l~one 3 - - . ..
_ ....... __ EXA~q PLE 15 Activity against the comstock mealybug Slices of a pumpkin bearing comstock mealybugs (Pseudococcus comstocki) were dipped for 30 seconds into a diluted ~.vettable powder prepared as described in Exarnple 8 to the concentration indicated in Table 9 and containing 0, 02 % of Gramin. Thc slices were lhen placed into petri dishes covercd ~ith filtcr papers.
Thc percentage mortallty of the comstock mealyb~lgs was asscssed aftcr 1 day and after 5 days and tlle rcsults are repolled in Table 9.
. .

41, . . _ . .

. , ,' ':

~hl91713 .
Table 9 _ ___ ___________.____ ~ , __~
Test Adult female 1st to 2nd instar la~vae Conc. No No. Mortality No~ Mortality . before (%) __ __ before _ _ %) __ dippiny 1 day 5 days dipping 1 day 5 days ___. ____ __ _ _ _ __._ _ _ _ __ ___ 1 20 100 _ 198 100 _ . 3 20 100 _ 23~ 100 _ ppm 7 20 100 _ - 215 100 . _ __ _ 14 _ ___100 ___ 162 100 1 20 85 ] 00 206 99 100 . 3 20 90 100 210 99 99 00 7 20 90 95 181 ~8 99 _ _ None 20 20 30 88 20 20 .. ___ __ , . _ .

42.

Claims (6)

THE EMBODIMENTS OF THE INVENTION IN WHICH AN EXCLUSIVE
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:

1. Compounds of formula (II):

(II) wherein R1 represents a hydrogen atom, a lower alkyl group or a halogen atorm; R2 represent a hydrogen atom, a lower alkyl group or a phenyl group; R3 represents a hydrogen atom, a lower alkyl group or a phenyl group; Y represents a halogen atom; and n is 1 or 2.

2. 2-chloromethyl-5-methyl-4-isoxazolin-3-one.

3. 2-(1-chloroethyl)-5-methyl-4-isoxazolin-3-one.

4. 4-chloro-2-chloromethyl-5-methyl-4-isoxazolin-3-one.

5. 4-chloro-2-chloromethyl-5-methyl-4-isoxazolin-3-one.

6. 2-(2-bromoethyl)-5-methyl-3-oxo-4-isoxazoline.