GB2146981A - N-substituted tetrahydrothiazines process for their preparation and-their use as pesticides - Google Patents

Abstract

N-substituted 2-nitomethylene-tetrahydro-2H-1,3-thiazines of the general formula: <IMAGE> in which n represents 0 or 1, and R represents a haloacetyl, dihaloacetyl, trihaloacetyl, alkoxyacetyl, haloalkoxyacetyl or alkoxyalkoxyacetyl group, or a cycloalkylsulphonyl group optionally substituted by one or more halogen atoms and/or alkyl, haloalkyl, alkenyl or haloalkenyl groups, have useful pesticidal properties.

Description

SPECIFICATION N-substituted tetrahydrothiazines, process for their preparation, and their use as pesticides This invention relates to N-substituted nitromethylene-tetrahydrothiazines, to processes for their preparation and to their use as pesticides, in particular against insect pests.

Certain 2-nitromethylene-tetrahydro-2H-1-,3-thiazines and their use as pesticides are known from UK Patent 1,513,951. However, although these thiazines possess a high level of insecticidal activity they suffer from the disadvantage of being unstable to light and, thus, show little persistence under field conditions. The Applicant has now found that this light-stability problem can be overcome by employing a new class of insecticidally-active thiazines.

Accordingly the invention provides an N-substituted 2-nitromethylene-tetrahydro-2H-1 ,3-thiazine of the general formula:

in which n represents 0 or 1, and R represents a haloacetyl, dihaloacetyl, trihaloacetyl, alkoxyacetyl, haloalkoxyacetyl or alkoxyalkoxyacetyl group, or a cycloalkylsulphonyl group optionally substituted by one or more halogen atoms and/or alkyl, haloalkyl, alkenyl or haloalkenyl groups.

In the group R, any halogen atom is preferably a fluorine or, especially, chlorine or bromine atom, and if two or more halogen atoms are present these may be the same or different. Any alkyl or alkoxy moiety preferably has up to 4, especially 1 or 2, carboy atoms. Acycloalkyl moiety preferably has 3 to 6 ring carbon atoms. Any alkenyl moiety preferably has 2 to 4 carbon atoms.

Preferably R represents a mono-, di- ortri-, chloro-, bromo- orfluoro-acetyl group, a methoxy- or ethoxy-acetyl group, or a cycloalkylsulphonyl group having 3 to 6 ring carbon atoms and optionally substituted by one or more chlorine atoms and/or methyl groups.

For example, R may represent a chloroacetyl, dichloroacetyl, bromoacetyl, methoxyacetyl or cyclopropy lsulphonyl group.

Preferably n isO.

It will be appreciated that the compounds of formula I are capable of existing in different geometrically isomeric forms. The invention includes both the individual isomers and mixtures of such isomers.

The invention includes a process for the preparation of the N-substituted 2-(nitromethylene)-tetrahydro 2N-1 3-thiazines of formula I, which comprises reacting the compound of formula:

with an acyl halide of formula RHal in which R is as defined above, and Hal represents a Halogen, preferably chlorine, atom, in the presence of a base, to produce a compound of the general formula I in which n isO; and if desired, oxidising the resulting compound of the general formula I into the corresponding compound of the general formula I in which n is 1.

The base is preferably an organic base such as a tertiary amine, for example a trialkylamine, triethylamine being particuiarly preferred. The reaction is suitably carried out at a temperature of 0 C or below, for example at a temperature from -75 to - 10'. The reaction is suitably carried out in an organic solent, for example, a chlorinated hydrocarbon such as dichloromethane, an ether such as tetrahydrofuran, or an amide such as dimethylformamide.

Compounds of the general formula I in which R represents an unsubstituted cycloalkylsulphonyl group and n is 0 may be prepared by an alternative procedure which comprises reacting a compound of the general formula

in which Hal represents a halogen atom and m represents the number of carbon atoms in the cycloalkyl ring, with a base. Suitable bases include sodium hydride. Compounds of the general formula Ill are described and claimed in UK Patent Application No. 8308258 (Publication No.2118177).

The compounds of formula I in which n is 1 may be prepared by oxidising the corresponding derivative in which n is 0. This may be carried out using conventional oxidising agents, for example peracids such as m-chloroperbenzoic acid, or potassium hydrogen persulphate. Conveniently the derivative to be oxidised is dissolved in a suitable solvent, for example a chlorrinated hydrocarbon solvent such as chloroform or dichloromethane, or a liquid alkanol such as ethano' As mentioned above the N-substituted 2-(nitromethylene)-tetrahydro-2H-1,3-thiazines of the invention are of interest as pesticides particularly against insect pests.They exhibit activity against such pests as the larval caterpillar or worm forms of insects, for example, of the genus Spodoptera and of the genus Heliothis. The compounds also exhibit acceptable stability towards light and oxidation.

Accordingiythe invention includes pesticidal compositions comprising a substituted 2-(nitromethylene)tetrahydro-2H-1 ,3-thiazine of the invention together with a carrier.

Such a composition may contain a single compound or a mixture of several compounds of the invention. It is also envisaged that different isomers or mixture of isomers may have different levels or spectra of activity and thus compositions may comprise individual isomers or mixtures of isomers. The invention further provides a method of combating pests, particular insect pests, at a locus, which comprises applying to the locus a pesticidally effective amount of compound or composition according to the present invention.

A carrier in a composition according to the invention is any material with which the active ingredient is formulated to facilitate application to the locus to be treated, which may for example be a plant, seed or soil, or to facilitate storage, transport or handling. A carrier may be a solid or a liquid, including a material which is normally gaseous but which has been compressed to form a liquid, and any of the carriers normally used in formulating pesticidal compositions may be used. Preferably compositions according to the invention contain 0.5 to 95% by weight of active ingredient.

Suitable solid carriers include natural and synthetic clays and silicates, for example natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminium silicates, for example attapulgites and vermiculites; aluminium silicates, for example kaolinites, montomorillonites and micas; calcium carbonate; calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminium silicates; eiements, for example carbon and sulphur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes; and solid fertilisers, for example superphosphates.

Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons, for example benzene, toluene and xylene; petroleum fractions, for example kerosine and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchloroethylene and trichloroethane. Mixtures of different liquids are often suitable.

Agricultural compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface-active agent facilitates this process of dilution. Thus preferably at least one carrier in a composition according to the invention is a surface-active agent. For example the composition may contain at least two carriers, at least one of which is a surface-active agent.

A surface-active agent may be an emulsifying agent, a dispersing agent or a wetting agent; it may be nonionic or ionic. Examples of suitable surface-active agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation of fatty acids or aliphatic amines or amides containing at least 12 carbon atoms in the molecule with ethylene oxide and/or propylene oxide; fatty acid esters or glycerol, sorbitan, sucrose or pentaerythritol; condensates of these with ethylene oxide and/or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide and/or propylene oxide; sulphates or sulphonates of these condensation products; alkali or alkaiine earth metal salts, preferably sodium salts, of sulphuric or sulphonic acid esters containing at least 10 carbon atoms in the moleculc, for example sodium lauryl sulphate, sodium secondary alkyl sulphates, sodium salts or sulphonated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulphonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide.

The compositions of the invention may for example be formulated as wettable powders, dusts, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates and aerosols. Wettable powders usually contain 25, 50 or 75% w of active ingredient and usually contain in addition to solid inert carrier, 3-10% w of a dispersing agent and, where necessary, 0-10% w of stabiliser(s) and/or other additives such as penetrants or stickers. Dusts are usually formulated as a dust concentrate having a similar composition to that of a wettable powder but without a dispersant, and are diluted in the field with further solid carrier to give a composition usually containing 1/2-10% w of active ingredient.Granules are usually prepared to have a size between 10 and 100 BS mesh (1.676-0.152 mm), and may be manufactured by agglomeration or impregnation techniques. Generally, granules will contain 1/2-75% w active ingredient and 0-10% w of additives such as stabilisers, surfactants, slow release modifiers and binding agents. The so-called "dry flowable powders" consist of relatively small granules having a relatively high concentration of active ingredient. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, co-solvent, 10-50% w/v active ingredient, 2-20% w/v emulsifiers and 0-20% w/v of other additives such as stabilisers, penetrants and corrosion inhibitors.Suspension conentrates are usually compounded so as to obtain a stable, non-sedimenting flowable product and usually contain 10-75% w active ingredient, 0-5-15% w of dispersing agents, 0.1-10% w of suspending agents such as protective colloids and thixotropic agents, 0-10% of other additives such as defoamers, corrosion inhibitors, stabilisers, penetrants and stickers, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formation to assist in preventing sedimentation or as antifreeze agents for water.

Aqueous dispersions and emulsions, for example compositions obtained by diluting a wettable powder or a concentrate according to the invention with water, also lie within the scope of the invention. The said emulsions may be of the water-in-oil or of the oil-in-water type, and may have a thick 'mayonnaise'-like consistency.

The compositions of the invention may also contain other ingredients, for example other compounds possessing pesticidal properties.

The thermal stability of the compounds and compositions of the invention may often be improved by the addition of stabilizing amounts, usually 10-100%w based on the active compound, of certain organo nitrogen compounds such as urea, dialkylureas, thiourea or guanidine salts or alkali metal salts of weak acids such as bicarbonates, acetates benzoates.

The invention is illustrated further in the following Examples.

Example 1 3-Cycloprop ylsulphon yl-2-nitromethylen e-tetrah ydro-2H- 1,3-thiazine To 2-nitromethylene-tetrahydro-2H-1,3-thiazine (4.89) in dichloromethane (100ml) at -15 C under nitrogen was added triethylamine (5ml).3-Chloropropyl sulphonyl chloride (5.9g) in dichloromethane (50ml) was then added dropwise over 25 minutes. The mixture was allowed to warm to room temperature, stirred for 1 hour, then washed twice with 2% aqueous HCI. The organic phase was dried over Mg04 and removed under reduced pressure to yield a solid which was triturated with methanol to give 892mg of 3-(3-chloropropylsu Iphonyl )-2-nitromethylene-tetrahydro-2H-1 ,3-thiazine, melting point 98-990C.

This compound (10g0 in acetone (700my) was heated under refluxfor 16 hours with sodium iodide (17,59).

The solvent was then removed under reduced pressure and the residue was partitioned between water and dichloromethane. The organic phase was dried (mgSO4) and the solvent was then removed under reduced pressure. The residue was recrystallised from dichloromethane to yield (3-(3-iodopropylsulphonyl)-2 nitromethylene-tetrahydro-2H-1,34hiazine as a yellow crystalline solid melting point 106-109"C.

This compound (0.5 g) was dissolved in hexamethylene-phosphoramide (5ml) and sodium hydride (32.5mg) was added under nitrogen at O"C over 2 hours. The mixtue was stirred for a further 2 hours at O"C, and then extracted with diethyl ether, washed with 2% aqueous HC1, dried (MgSO4) and purified by chromatography over silica using dichloromethane as eluent. The desired product was obtained in 57% yield, melting point 92-95"C.

Elemental Analysis C H N Calculated 36.4 4.6 10.6 Found 36.1 4.7 10.4 Example 2 3-Chloroacetyl-2-nitromethylene-tetrahydro-2H- 1,3-thiazine Chloroacetyl chloride (9OOmg) in dichloromethane (1 Omis) was added dropwise, over 25 minutes, under nitrogen, to a stirred mixture of 2-nitromethylene-tetrahydro-2H-1,3-thiazine (1.0g) and triethylamine (2mls) in dichloromethane (1 OmIs) at -20"C. The mixture was allowed to warm to room temperature, and stirred for 10 minutes. It was then washed with 2% aqueous HC1, dried (MgSo4), and evaporated under reduced pressure. The residue was purified by chromatography over silica using 1% methanol in dichloromethane as eluent.Trituration of the resulting product with diethyl ether gave 456mg of the desired crystalline product, melting point 104"C.

ElementalAnalysis C H N Calculated 35.6 3.8 11.9 Found 35.3 3.8 11.8 Examples 3 to 5 By methods analogous to that of Example 2, further compounds of the general formula I were prepared.

Details are given in Table 1.

TABLE 1 Example In the General Formula I Melting Point ElementalAnalysis No.

R n "C C H N 3 CO.CHCI12 0 102-103 Calc. 31.0 3.0 10.3 Found 31.1 3.1 10.3 4 CO.CH2Br 0 96-98 Calc. 29.8 3.2 10.0 Found 31.6 2.2 10.2 5 CO.CH2.oCH3 0 62-64 Calc. 41.4 5.2 12.1 Found 41.35.3 12.1 Example 6 Pesticidal A ctivity The pesticidal activity of the compounds of the invention was assesed against the following insect pests.

Spodoptera littoralis (S.l.) Aedes aegypti (A.a) Musca domestica (M.d) Aphis fabae (A.f.) The test methods employed for each species appear below; in each test, unless otherwise stated, a 0.2% solution or suspension of each test compound in 16.7% acetone in water containing 0.04% Triton X-l 00 (Trade Mark) was sprayed onto the test species; controls were sprayed with a control solution of water, acetone and Triton X-100 (Trade Mark) in the same proportions. The tests were all conducted under normal insectary conditions 23"C t 2"C (fluctuating light and humidity).

(i) Spodoptera littoralis (S.I.) Second instar larvae were used in the tests. Each test solution and the control solution was sprayed onto a separate petri dish containing a nutrious diet on which the Spodoptera littoralis larvae had been reared.

When the spray deposit had dried each dish was infested with 10 2nd instar larvae. Mortality assessments were made 1 and 7 days after spraying and the percentage mortality calculated.

(ii) Aedes aegypti (A.a.) Early 4th instar larvae were used in the tests. Test solutions were made up to 3 ppm of active ingredient in water containing 0.04% Triton X-l 00 (Trade Mark); acetone was initially present to aid solution, but was subsequently allowed to evaporate off.

Ten early 4th instar larvae were placed in 100 ml of the test solution. After 48 hours, larval mortality (as a percentage) was recorded.

Any surviving larvae were then fed with a small quantity of animal feed pellets and the final percentage mortality of adults and pupae made when all the larvae had either pupated and turned into adults, or died.

(iii) Misca domestica (M.d.) Batches often 2to 3 day old milk-fed adult female houseflies (Musca domestica) anaesthetized using carbon dioxide were placed on petri dishes lined with filter paper. The dishes were sprayed with the test formulations using a spray machine operating on a logarithmic dilution principle. The flies were subsequently retained in the petri dishes and were fed with a dilute milk solution which was dripped down the side of the petri dish and absorbed onto the filter paper. Mortality was assessed after 24 hours.

(iv) Aphis fabae (A.f) Tests were carried out on adult black bean aphids Aphis fabae. Pairs of broad bean leaves on filter paper in petri dishes were sprayed side by side with uncounted quantities of aphids in small gauze-covered containers. After passing through the spray the aphids were tipped onto the leaves and lids were placed on the petri dishes. Mortality was assessed after 24 hours.

The results of these tests are shown in Table 2 in which the test species are identified by the initials noted above and the activity of each compound is expressed in terms of the percentage mortality: A denotes 90-100% mortality B denotes 50-80% mortality C denotes 0-40% mortality.

TABLE 2 Compound of InsecticidalActivity Example No. SI. A.a. M.d. A.f.

iday 7days 2 days Final 1 A A C C B B 2 A A C A A B 3 A A C A A C 4 A A B A A A 5 A A C A A A

Claims (9)

1. An N-substituted 2-nitromethylene-tetrahydro-2H-1 3-thiazine of the general formula:

in which n represents 0 or 1, and R represents a haloacetyl, dihaloacetyl, trihaloacetyl, alkoxyacetyl, haloalkoxyacetyl or alkoxyalkoxyacetyl group, or a cycloalkylsulphonyl group optionally substituted by one or more halogen atoms and/or alkyl, haloalkyl, alkenyl or haloalkenyl groups.

2. A compound as claimed in claim 1, in which R represents a mono-, di- ortri- chloro-, bromo- or fluoro-acetyl group, a methoxy- or ethoxy-acetyl group, or a cycloalkylsulphonyl group having 3 to 6 ring carbon atoms and optionally substituted by one or more chlorine atoms and/or methyl groups.

3. A compound as claimed in claim 2, in which R represents a chloroacetyl, dichloroacetyl, bromoacetyl, methoxyacetyl or cyclopropylsulphonyl group.

4. A compound as claimed in any one of claims 1 to 3, in which n isO.

5. A process for the preparation of a compound as claimed in claim 1, which comprises reacting the compound of formula:

with an acyl halide of formula RHal in which R has the meaning given in claim 1 and Hal represents a halogen atom, in the presence of a base, to produce a compound of the general formula I given in claim 1 in which n isO; and if desired, oxidising the resulting compound of the general formula I into the corresponding compound of the general formula I in which n is 1.

6. A process for the preparation of a compound as claimed in claim 1 in which R represents an unsubstituted cycloalkylsuiphonyl group and n =0, which comprises reacting a compound of the general formula

in which Hal represents a halogen atom and m represents the number of carbon atoms in the cycloalkyl ring, with a base.

7. A pesticidal composition which comprises a compound as claimed in any one of claims 1 to 4, together with a carrier.

8. A composition as claimed in claim 7, which comprises at least two carriers, at least one of which is a surface-active agent.

9. A method of combating pests at a locus, which comprises applying to the locus a pesticidally effective amount of a compound as claimed in any one of claims 1 to 4 or a composition as claimed in either claim 7 or claim 8.