CA1121349A - Insecticidal 2-substituted-imino-3-alkyl-5-dialkoxy- phosphinotioyloxy-6h-1,3,4-thiadiazine - Google Patents

Abstract

ABSTRACT
Novel thiadiazin-5-ones of the formula:

Description

L3~

This invention relates to novel substituted thiadiazinones useful as intermediates in the preparation o certain insecticides, which are the subject of our Copending Application Serial No. 322 912, filed March 7, 1979.
Chemical Abstracts, ~ol. 80, 82906 p ~1974) discloses thiadiazinones and their mono- and dithiophosphates.
The compounds of the invention are represented by the formula

2 ~ 3 ~
(I) R -N=C2 4 NH

Sl 5 C=0 wherein R is alkyl of 1 to 6 carbon atoms and R is alkyl of 1 to 6 carbon atoms, alkeny~l o~ 3 to 6 carbon atoms, cycloalkyl of 5 to 6 carbon atoms, lQ phenyl, or phenyl substituted wlth 1 or 2 substituents selected from the group consisting of alkyl of 1 to ~ carbon atoms, fluoro, chloro, bromo, iodo, nitro, trifluoromethyl, trichloromethyl, tribromomethyl and alkoxy of 1 to 4 carbon atoms.
Representative alkyl R and R2 groups include methyl, ethyl, iso-propyl, n-butyl, isohexyl and n-hexyl.
Representative substituted phenyl R2 groups include 4-methylphenyl, 2,4-dimethylphenyl, 2-fluorophenyl, 3,5-dichlorophen~l, 3-bromophenyl, 4-~odophenyl, 2-methyl-4-chlorophenyl, 4-nitrophenyl 3-trichloromethylphenyl, 2-methoxyphenyl and 2-chloro-4-nitrophenyl. Representative alkenyl R2 groups 2Q are allyl, 2-butenyl and 3-hexenyl.
Preferably Rl is lower alkyl of 1 to 3 carbon atoms, especially methyl.
Preferred alkyl R2 groups are alkyl o~ l to 4 carbon a~oms and pre-ferred aryl R2 groups are phenyl and phenyl substituted with 1 to 2 substitu-ents selected from alkyl of 1 to 4 carbon atoms, fluoro, chloro, bromo, trl-fluoromethyl and tr~chloromethyl. Preferably, R2 is alkyl of 1 to 4 carbon L3~9~

atoms, especi~ally ethyl.
A preferred class o~ thiadiazlnones of formula I is that wherein Rl is lower alkyl o~ l to 3 carbon atoms, especially methyl and R2 is alkyl of l to 6 carbon atoms.
The compounds of the invention are novel compounds and are prepared by the cyclization of a semithiocarbazide ~IT~ with a haloacetic anhydride ~ , as depicted in the following reaction ~
S

R -NH-C-NH-NH2 ~ ~X CH2C0)20 ~ ~I) ~1) Rl ~II~ ~III) wherein Rl and R2 have the same meaning as pre~iousl~ stated, and x is chloro or bromo, preferably chloro.
Reaction ~1) is generally conducted by reacting substantially equi-molar amounts of the semithiocarbazide ~II) and the haloacetic anhydride ~III) in the liquid phase. The molar ratios of semithiocarbazide to anhydride ~III) generally var~ from about 1:1.2 to 1.2:1, although molar ratios of from about 1:1.1 to 1.1:1 are preferred. The reaction is normally conducted in an inert liquid diluent, e.g., organic solvents such as chlorinated hydrocarbons. The reaction is conducted at a temperature of from about 0 *o the boiling point of the diluent, although temperature~;from about 25~C to loOQC are preferred.
The reaction is conducted at or above atmospheric pressure. Generally, the reaction is completed within one-half to 24 hours. The product ~I) is isolat-ed and purified by conventional procedures such as extraction, fil~ration, crys-tallization and chromatography. Generally, when the thiadiazinone product ~I) has an aliphatic imino substituent (R2~, the product is most conveniently isolated as a hydrogen halide salt.
The thiadiazin-5-one products ~I) may~also be prepared by reacting the semithiocarbazide (II) with an alkyl halo~hioacetate ~IV) as depicted in the following reaction ~2):

S o R -NH-C--NH-N~l2 ~ XCH2CSR -~ ~I) (2) R

~II) (IV) whereln Rl, R2 and X have the same meaning as previously stated and R is alkyl of 1 to 6 car~on atoms, preferabl~ of 1 to 3 carbon atoms.
Reaction ~2) is generally conducted by reacting substantially equi-molar amounts of the semithiocarbazide (II) and the halothioacetate (IV3 in the liquid phase. The molar ratios of semithiocarbazide to halothioacetate CIV3 generally vary from about 1:1.2 to 1.2:1, although molar ratios of from about 1:1.1 to 1.1:1 are preferred. The reaction is normally conducted in an inert li~uid diluent. Suitable inert organic diluents include alkanones such as acetone, methyl ethyl ketone;acyclic alkyl ethers such as dimethoxyethane and dlbutylether; cyclic ethers such as dioxane or tetrahydrofuran; halo-alkanes such as dichloromethane; and aromatic compounds such as benzene, toluene, and chloro~enzene. Generally, the amount of diluent employed ranges from 1 to 5Q mols per mol of sem~thiocarbazide ~II). The reaction is conduc~-ed at a temperature of from about 0C to the boiling point of the diluent~
although temperatures from about 25QC to 100C are preferred. The reaction is conducted at or above atmospheric pressure. Generally, the reaction is completed within one-half to 24 hours. The product ~I) is isolated and puri-2Q fled ~y conventional procedures such as extraction, filtration, crystalliza-tion and chromatography. Generally, ~hen the thiadiazinone product ~I) has ; an aliphatic imino substituent (R2), the product is most conveniently isolated as a hydrogen halide salt.
Utilit~
The thiadiazin-5-one çompounds of this in~ention may be used in the preparation of insecticidal thiadiazine compounds ~) by additlon of a di-alkoxyhalothiophosphate (Vl) to a compound of formula ~I~, as depicted in the ~ollowing reaction (33:

34~

Il S R -N=C N S
R2 N C ,' N ~ NH X-P-oR3 ~ S~ ll ~ 3 S C=O R C~I2 1R
CH2~
~) C~I) cv) wherein Rl, R2 and x ha~e the samè meaning as stated before (see reaction ~1)) and R3 and R4 are alkyls of from 1 to 6 carbon atoms, preferably of 2 to 4 carbon atoms.
Reaction (3) is generally conducted by reacting substantially equi-molar amounts of the thiadiazinone (I) and the thiophosphate (~I), i.e., the molar ratios of thiadiazinone (I) to thiophosphate ~I) generally vary from about 1:1.2 to 1.2:1, although molar ratios from about 1:1.1 to 1.1:1 are preferred. A substantially equivalent amount of a base material is used to scavenge the hydrogen halide b~-product. Such bases are preferably inorganic bases, e.g., alkali metal carbonates such as sodium carbonate and potassium carbonateJ and alkali metal bicarbonates such as sodium bicarbonate. The molar ratio of base to the thiadiazinone (I) is generally about 1.1:1 to 1:1.
The reaction is conducted in an inert liquid organic diluent. Suitable inert organic diluents include alkanones such as acetone, methyl ethyl ketone;
acyclic alkyl ethers such as dimethoxyethane and dibutylether; cyclic ethers suc~ as dioxane or tetrahydrofuran; haloalkanes such as dichloromethane and aromatic compounds such as benzene, toluene, and chlorobenzene. Generally, the amount of diluent employed ranges from 1 to 50 mols per mol thiophosphate 2a (VI~.
Reaction ~3) is suitably conducted at a temperature of rom about 15C to the boiling point of the diluent, although temperatures of from about 20C to 100C are preferred. The reaction is conducted at or above atmos-pheric pressure. The reaction ~ime will, of course, vary depending on the reaction temperature and the particular reactants employed. Generally, how-L39~9 ever, the reaction time varies from several minutes to 24 hours. The thia-diazine product CV) is lsolated from the reaction mixture by conventional procedures, e.g., extraction, chromatography, crystallization, etc.
R0action ~3) ma~ also be conducted with the hydrogen halide salts o~ the thiadiazinone ~. In this modification of reaction (3), two equival-ents of the ~ase material is used, i.e., the molar ratio of base to thiadi-azlnone is generally about 2.2:1 to 2:1. lt is generally preferred to use the hydrogen halidesalt when the imino substituent (R2) of the thiadiazinone CI) iS aliphatic .
The followlng Examples illustraie the invention and the utility of the compounds of this invention in the preparation of t~e insecticidal thia-diazine compounds ~V).

Example 1 - Preparatlon of 2-~3,4-dichlorophenylimino)-

3-meth~l-tetrahydro-6H-1 J3 ,4-thiadiazin-5-one To a stirred solution of 37.5 g ~0.15 mol) 2~meth~1-4-~3,4-di-chlorophen~l)semithiocarbazide in 200 ml dichloromethane was added 25.5 g (0.015 mol~ chloroacetic anhydride. The resulting reaction mixture was heated under reflux for 16 hours, cooled, neutralized with sodium bicarbonate, washed with water, dried over magnesium sulfate and e~aporated under reduced prassure to give an o~l~ solid. The solid was slurried with ether, filtered and dried to glve 12 g of the product, as a grey solld, m.p. 118 - 120C. This pro-duct is tabulated in Table A as compound No. A-6.

Example 2 - Preparation of 2-~3,4-dichloro~henylimino)-3-methyl-5-diethoxyphosphinothioyloxy)-2,3-dihydro-6H-1,3,4-thiadiazine A slurry of 14 g ~0.048 mol) 2-~3,4-dichlorophen~limino)-3-me~hyl-tetrahydro-6H-1,3,4-thiadiazin-5-one, 7 g ~0.048 mol) 01potassium bicarbonate, and 9.1 9 (0.048 mol) diethylchlorothio-02 phosphate in 200 ml acetone was heated under reflux for 8 hours, 03 cooled and stirred at about 25C for overnight. The reaction 04 mixture was filtered and evaporated under reduced pressure to give 05 an oil. The oil was chromatographe~ on silica gel using 50/50 06 petroleum ethyl/diethyl ether as the eluant to give 11 9 of the 07 product, as a yellow oil. This product is tabulated in Table B, 08 as compound B-7.
09Example 3 -- Preparation of 2-(t-butylimino)-3-10 .methyl-tetrahydro-6H-1,3,4-thiadiazin-~5-one hydrochloride 12To a stirred solution of 16.1 9 (0.1 mol) 2-methyl-4-t-13 butylsemithiocarbazlde in 200 ml dichloromethane was added slowly 1417.1 9 (0.1 mol) chloroacetic anhydride. The resulting solution was stirred at about 25C for about 8 hours. The reaction mixture 16 was filtered to ~ive 14 9 of the product, as a white solid, m.p., 17224-225C. The infrared spectrum of the product showed carbonyl 18 absorption at 5.95 micron. Elemental analysis for CgHl~ClN3OS
19 showed:
20Calc. Found 21~S 13O5 13.3 22%Cl 14.9 15.5 25Example 4 -- Preparation of 2-(t-butyl-26imino)-3-methyl-5-diethoxyphosphino-27thioylo~y-2,3-dihYdro-6H-1,3~4 thiadiaziQe 28A slurry of 10.0 ~ (0.0421 mol) 2-(t-butylimino3-3-29methyl-6H-1,3,4-thiadiazin-5-one, 11.6 ~ (0.0842 mol) potassium 30carbonate and 8.2 9 (0.0421) diethylchlorothiophsphate in 200 ml 31 acetone was heated under reflux for 8 hours, The reaction mixture 32 cooled, stirred overnight, filtered and evaporated under reduced 33 pressure to give an oil residue. The residue was dissolved in 34 dichloromethane, washed with water, dried over magnesium sulfate and evaporated under reduced pressure. The crude product was then 36 chromatographed on silica gel using diethyl ether as the eluant.

37 ~7-3~
01 The purified product (6 9) was an amber oil. The product is tabu-02 la~ed in Table B as Compound No. B-l.
03 Example 5 -- Preparation of 2-(t-butylimino)-3-04 methyl-6H-1,3,4-thiadiazin-5-one hydrobromide__ 05 To a stirred solution of 5.75 9 (0.05 mol) 2-methyl-4-t-06 butylsemithiocarbazide in 50 ml dichloromethane was added dropwise 07 9.15 9 (0.05 mol~ ethyl alpha-bromothioacetate at 25C. The reac-08 tion mixture was stirred at 25C for 20 minutes (slightly exo-09 thermic reaction) and then heated under reflux for 4 hours. After io ~ ~ cooling, the precipitated solid was filtered, washed with hexane 11 and dried to give 7.3 g of product, m.p. 215-216C.
12 The compounds tabulated in Tables A and B were prepared 13 by procedures similar to those of Examples 1-5. The structure of 14 each compound tabulated in Tables A and B was confirmed by nuclear magnetic resonance and/or infrared spectroscopy.

34~

03 Compounds of the formula CJ~3 /N~
R -N=C NH
S /C=O
07 C~
08 Elemental Analysis No. R2 m.p.,C Calc. ~ound Calc. Found Calc. Found ~! 143-145 -- -- ~~ ~~ 12.51 13.21 13 A-2 i-C 3~7 122-124 ~ 14.11 13,81 14 A 3 n-C3H7 126-130 37.6 35.6 603 5-9 18.2 17.2 lS A-4 t-C4Hg 127 129 40.4 39.3 6.8 6.6 17.7 17.1 16 A-5 3-CF3-~ 83~84 45.7 44.4 3OS 4.1 1405 15.0 17 A 6 3,4-C12-~118-120 41.4 40.7 3.1 3.1 14.5 14.1 18 A-7 ~ 140-144 46.6 43.4 4.7 4.8 16.3 15.5 19 A-8 cyclohexyl 133-13545.6 47.1 6.9 7.8 15.9 16.8 A-9 CH2=CHCH268-70 37.9 35.1 5.5 5.6 19.0 17.9 21 A-10 ~ 143-145 54.3 5501 5.0 5.2 19.0 19.4 23 lSulfur analysis ~ represents phenyl.

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~2~3~g The thiadiazine compounds ~V) were tes*ed as follows to illustrate their insecticldal activi~t~. Test results are reported in Table C.
Test Procedures Aphid (Aphis gossypii Glover): An acetone solution of the candi-date toxicant containing a small amount of nonionic emulsifier was diluted with water to 40 ppm. CucumBer leaves infested wlth the cotton aphids were dipped in the toxlcant solutlon. Mortallty readlngs were then taken after 24 hours.
Two-spotted Mlte tTetramuchus urtlcae): An acetone solutlon of the candidate toxicant containing a small amount of nonionic emulsifier was dl-luted wlth water to 40 ppm. Lima bean leaves whlch were lnfested wlth mltes were dlpped ln the toxlcant solution. Mortality readings were taken after 24 hours.
~lousefly (Musca domestica L.): A 500 ppm acetone solutlon of the candidate toxicant was placed in a microsprayer ~atomizer). A random mixture of anesthetized male and female flles was placed in a container and 55 mg of the above-descrlbed acetone solutlon was sprayed on them. A lld was placed on the container. A mortality reading was made after 24 hours.
AmerIcan Cockroach (Periplaneta americana L.): A 500 ppm acetone 2Q solution o~ the candidate toxicant was placed in a microsprayer (atomizer).
A random mlxture of anesthetlzed male and female roaches was placed in a con-tainer and 55 mg of the above-descrlbed ~cetone solutlon was sprayed on them.
A lld was placed on the container. A mortallty reading was made after 24 hours.
Al~alfa Weevil (~. brunnelpennis Boheman): A 500 ppm acetone solu-tlon of the candidate toxicant was placed in a mlcrosprayer (atomlzer). A
random mlxture of anesthetized male and female flles was placed in a container and 55 mg of the above-described acetone solution was sprayed on them. A lid was placed on the contalner. A mortalit~ reading was made after 24 hours.

3~
01 Rootworm (Diabrotica u. undecimpunctate Mannerheim): A batch of 02 20-30 two-day-old Diabrotica eggs was placed on the bottom edge of 03 a 236-ml plastic cup. The cup then received the following 04 materials:
OS (1) 66 g soil treated with lS ppm of the test compound; (2) 15 06 ml water; (3) 10 presoaked (in water for 2 hours) corn seeds 07 evenly distributed on the soil surface; (4) 66 9 soil treated with 08 lS ppm of test compounds; and (5) 15 ml water. The cup was placed 09 in an incubation chamber and lightly watered as needed to keep the soil damp. After 14-16 days the test cup was examined under a dis-11 secting microscope by observing the corn roots and soil through 12 the clear plastic walls of the cup. Control of newly hatched 13 larvae was rated by visually evaluating the degree of corn root 14 damage by feeding larvae in conjunction with visible presence of live and/or dead larvae.
16 TABLE C -- Insect Control~ %

19 No. Aphid Mite ~ Roach Weevil Rootworm Loo~er 23 B-3 100 99 10~ 100 100 0 100 26 B~6 99 94 100 - 100 78 50 27 B-7 0 70 22 ~ 0 98 100 29 B~9 100 50 22 0 100 100 80 33 The compounds of this invention are toxic to a variety 34 of crop and household pests, in addition to the typical pests exem-plified above. Like most agricultural chemicals, they are not 36 ~sually applied full strength, but are generally incorporated with 37 conventional biologically inert extenders or carriers normally 38 employed for facilitating dispersion of active ingredients for 39 agricultural chemical applications, recognizing the a~cepted ~act that the formulation an~ mode of application may affect the 41 activity of a material. The toxicants of this invention may be 13~5~

applied as sprays, dusts, or granules to the insects, their environment or hosts susceptible to insect attack. They may be formulated as granules of large particle size, as powdery dusts, as wettable powders, as emulsifiable concentrates, as solutions, or as any of several other known types of formu-lations, depending on the desired mode of application.
Wettable powders are in the form of finely divided particles which disperse readily in water or other dispersant. These compositions normally contain from 5-80% toxicant and the rest inert material which includes dis-persing agents, emulsifying agents, and wetting agents. The powder may be applied to the soil as a dry dust or preferably as a suspension in water.
Typical carriers include fuller's earth, kaolin clays, silicas, and other highly absorbent, readily wet, inorganic diluents. Typical wetting~ dispers-ing, or emulsifying agents used in agricultural formulations include, for ex-ample, the alkyl and alkylaryl sulfonates and sulfonates and their sodium salts; alkylamide sulfonates, including fatty methyl taurides; alkylaryl polyether alcohols, sulfated higher alcohols, and polyvinyl alcohols; poly-ethylene oxides; sulfonated animal and vegetable oils; sulfonated petroleum oils; fatty acid esters of polyhydric alcohols and the ethylene oxide addi-tion products of such esters; and the addition products of long chain mer-captans and ethylene oxide. Many other types of useful surface-active agents are available in commerce. The surface-active agent, when used, normally comprises from 1% to 15% by weight of the pesticidal composition.
Dusts are freely flowing admixtures of the ac~ive ingredient with finely divided solids such as talc, natural clays, kieselguhr, pyrophyllite, chalk, diatomaceous earths, calcium phosphates, calcium and magnesium car-bonates, sulfur, lime, flours, and other organic and inorganic solids which act as dispersants and carriers -for the toxicant. These finely divided solids have t ~ 349 an average particle size of less than about fifty microns. A typical dust formulation useful herein contains 75o silica and 25o of the toxicant.
Useful liquid concen-trates include the emulsifiable concentrates, ~hich are homogeneous liquid or paste compositions which are readily dis-persed in water or other dispersant, and may consist entirely of the toxicant with a liquid or solid emulsifying agent, or may also contain a liquid carrier, such as xylene, heavy aromatic naphthas, isophorone, and other non-volatile ~organic solvents. For application, these concentrates are dispersed in water or other liquid carrier, and normally applied as a spray to the area to be treated.
Other useful formulations for insecticidal applications include simple solutions of the active ingredient in a dispersant in which it is com-pletely sol~ble at the desired concentration, such as acetone, alkylated naph-thalenes, xylene, or other organic solvents. Granular formulations, wherein the toxicant is carried on relatively coarse particles, are of particular utility for aerial distribution or for penetration of cover crop canopy.
Baits, prepared by mixing solid or liquid concentrates of the toxicant with a suitable food, such as a mixture of cornmeal and sugar, are useful formula-tions for control of insect pests. Pressurized sprays, *ypically aerosols wherein the active ingredient is dispersed in finely divided form as a result of vaporization of a low-boiling dispersant solvent carrier, such as the Freons*, may also be used. All of these techniques for formulating and ap-plying the active ingredient are well known in the art.
The percentages by weight oF ~he toxicant may vary according to the manner in which the composition is to be applied and the particular $ype of formulation, but in general comprises 0.1 to 95% of the toxicant by weight of the pesticidal composition.

* Trade Mark 3~

The pesticidal compositions may be formulated and applied with other active ingredients, including other nemato-cides, insecticides, fungicides, bactericides, plant growth regulators, fertilizers, etc. In applying the chemical an effec-tive amount and concentration of the toxicants of this invention is, of course, employed.
The terms "insecticide" and "insect" as used herein refer to their broad and commonly understood usage rather than to those creatures which in the strict biological sense are classified as insects. Thus, the term "insect" is used not only to include small invertebrate animals belonging to the class "Insecta", but also to other related classes of arthropods, whose members are segmented invertebrates having more or fewer than six legs, such as spiders, mites, ticks, centipedes, worms and the like.

,

Claims (2)

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

1. A compound of the formula (I) wherein R1 is alkyl of 1 to 6 carbon atoms, and R2 is alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, cycloalkyl of 5 or 6 carbon atoms, phenyl or phenyl substituted with 1 or 2 substituents selected from the group consisting of alkyl of 1 to 6 carbon atoms, fluoro, chloro, bromo, iodo, nitro, trifluoromethyl, trichloromethyl, tribromomethyl, and alkoxy of 1 to 4 carbon atoms.

2. A method of preparing a compound of formula (I) as defined in claim 1, which comprises reacting a thiosemicarbazide of the formula wherein R1 and R2 are as defined in claim 1 with chloroacetic or bromoacetic anhydride in the liquid phase.