HK1139151B - Process for the oxidation of certain substituted sulfilimines to insecticidal sulfoximines - Google Patents

Description

Process for the oxidation of certain substituted sulfilimines to insecticidal sulfoximines

Technical Field

The present invention relates to a process for the preparation of insecticidal sulfoximines (sulfoximines) from certain substituted sulfilimines (sulfoximines).

Background

Substituted sulfilimines are useful intermediates in the preparation of certain novel pesticides, see, for example, U.S. patent application publication 2005/0228027. It would be beneficial to obtain sulfoximines efficiently and in high yield from the corresponding sulfilimines.

Disclosure of Invention

The present invention relates to a process for the oxidation of certain substituted sulfilimines, having the general formula (I),

wherein

Het represents:

x represents halogen, C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₂-C₄Haloalkenyl, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, CN, N0₂、SO_mR⁶Wherein m is an integer of 0-2, COOR⁴Or CONR⁴R⁵；

Y represents hydrogen, halogen, C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₂-C₄Haloalkenyl, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, CN, NO₂、SO_mR¹Wherein m is an integer of 0-2, COOR⁴、CONR⁴R⁵Aryl or heteroaryl;

n is an integer of 0 to 3;

l represents a single bond; or L represents-CH (CH)₂)_P-, in this case R¹S and L together represent a 4, 5 or 6 membered ring and p is an integer from 1 to 3; or L represents-CH (CH)₂OCH₂) -, in this case R¹S and L together represent a six-membered ring; or L represents-CH-, in which case L, R²Together with the common carbon to which they are attached represent a 4, 5 or 6 membered ring containing up to but not more than 1 heteroatom;

R¹is represented by C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₃-C₆Alkenyl radical, C₃-C₆Alkynyl, C₃-C₆Haloalkenyl, arylalkyl, heteroarylalkyl, or when R is¹R represents a 4, 5 or 6 membered ring when S and L together¹represents-CH₂-；

R²And R³Independently represent hydrogen, halogen, C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₂-C₄Alkenyl radical, C₂-C₄Alkynyl, C₂-C₄Haloalkenyl, C₁-C₄Alkoxy radical, C₁-C₄Haloalkoxy, CN, SO_mR⁶Wherein m is an integer of 0-2, COOR⁴、CONR⁴R⁵Arylalkyl, heteroarylalkyl, or R²And R³Form a 3-6 membered ring with the common carbon to which they are attached;

R⁴and R⁵Independently represent hydrogen, C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₃-C₆Alkenyl radical, C₃-C₆Alkynyl, C₃-C₆Haloalkenyl, aryl, heteroaryl, arylalkyl or heteroarylalkyl; and

R⁶is represented by C₁-C₄Alkyl radical, C₁-C₄Haloalkyl, C₃-C₆Alkenyl radical, C₃-C₆Alkynyl, C₃-C₆Haloalkenyl, arylalkyl or heteroarylalkyl;

the insecticidal sulfoximine of formula (Ia) has the structure:

wherein

R¹、R²、R³Het, L and n are as defined above. In the process, a sulfimine of formula I is oxidized to the corresponding sulfoximine of formula Ia as follows: contacting the sulfilimine with an oxidizing agent comprising ruthenium tetroxide or an alkali metal permanganate at a temperature of-10 to 45 ℃ in a suitable organic solvent that is substantially inert to strong oxidation conditions.

The process is well suited for the oxidation of sulfilimines of the following classes:

(1) a compound of formula (I) wherein Het is (6-substituted) pyridin-3-yl or (2-substituted) thiazol-5-yl, and wherein X is halogen or C₁-C₂Haloalkyl, and Y is hydrogen;

(2) a compound of formula (I) wherein R²And R³As defined above, R¹Is methyl, n is 1, and L is a single bond, the compound having the structure:

(3) a compound of formula (I) wherein n is 1, R¹S and L together form a standard 4, 5 or 6 membered ring, in which case L is-CH (CH)₂)_P-, and p is an integer from 1 to 3, and R¹is-CH₂-, the compound has the following structure:

(4) a compound of formula (I) wherein n is O, R¹S and L together form a standard 4, 5 or 6 membered ring, in which case L is-CH (CH)₂) p-and p is an integer from 1 to 3, and R¹is-CH₂-, the compound has the following structure:

Detailed Description

Throughout this application, all temperatures are in degrees Celsius and all percentages are by weight unless otherwise indicated.

The terms "alkyl", "alkenyl" and "alkynyl" as well as derivative terms such as "alkoxy", "acyl", "alkylthio", "arylalkyl", "heteroarylalkyl" and "alkylsulfonyl" as used herein include within their scope straight chain, branched chain and cyclic moieties. Typical alkyl groups are therefore methyl, ethyl, 1-methylethyl, propyl, 1-dimethylethyl and cyclopropyl. Unless otherwise indicated, each group may be unsubstituted or substituted with one or more substituents selected from but not including the following: halogen, hydroxy, alkoxy, alkylthio, C₁-C₆Acyl radical (C)₁-C₆acyl), formyl, cyano, aryloxy or aryl, provided that the substituents are sterically compatible and satisfy the rules of chemical bonding and strain energy (strain energy). The terms "haloalkyl" and "haloalkenyl" include alkyl and alkenyl groups substituted with one to the maximum possible number of halogen atoms, including all combinations of halogens. The term "halogen" or "halo" includes fluorine, chlorine, bromine and iodine, preferably fluorine. The terms "alkenyl" and "alkynyl" are intended to include one or more unsaturated bonds.

The term "aryl" refers to phenyl, indanyl (indanyl) or naphthyl. The term "heteroaryl" refers to a 5 or 6 membered aromatic ring containing one or more heteroatoms (i.e., N, O or S); these heteroaromatic rings may be fused with other aromatic systems. The aryl or heteroaryl substituents may be unsubstituted or substituted with one or more substituents selected from: halogen, hydroxy, nitro, cyano, aryloxy, formyl, C₁-C₆Alkyl radical, C₂-C₆Alkenyl radical, C₂-C₆Alkynyl, C₁-C₆Alkoxy, halo C₁-C₆Alkyl, halo C₁-C₆Alkoxy radical, C₁-C₆Acyl radical, C₁-C₆Alkylthio radical, C₁-C₆Alkylsulfinyl radical, C₁-C₆Alkylsulfonyl, aryl, C₁-C₆Alkyl C (O) O-, C₁-C₆Alkyl C (O) NH-, -C (O) OH, C₁-C₆Alkyl OC (O) -, -C (O) NH₂、C₁-C₆Alkyl NHC (O) -or (C)₁-C₆Alkyl radical)₂Nc (o) -, provided that the substituents are sterically compatible and satisfy the rules of chemical bonding and strain energy.

The sulfilimine starting materials of formula I are the subject of a patent application filed concurrently with this application, and some of them are disclosed in U.S. patent application publication No. 2005/0228027. They can be prepared from the corresponding sulfides according to schemes a and B below.

Compounds of formula (I) (wherein Het, R¹、R²、R³N and L are as defined above) may be prepared by the methods set forth in scheme a.

Scheme A

In scheme A, step a, the sulfide of formula (A) is imidized with chloramine T trihydrate (chloramine T trihydrate) in a polar solvent at 25-60 ℃ to provide N-toluenesulfonyl sulfimide of formula (B). In most cases, acetonitrile is the preferred imidizing solvent.

In scheme A, step B, N-tosylsulfilimine (B) is hydrolyzed in pure sulfuric acid to provide N-unsubstituted sulfilimine (C). The product was usually used directly in the next reaction without further purification.

In step C of scheme A, the nitrogen of sulfilimine (C) can be cyanated with cyanogen bromide in the presence of a base to provide N-substituted sulfilimine (I).

Compounds of formula (Ia) (wherein Het, R)¹、R²、R³N and L are as defined above) Can be prepared by the methods set forth in scheme B. Accordingly, the precursor sulfide is oxidized with iodobenzene diacetate in the presence of cyanamide at 0 ℃ to give sulfilimine (Ia). The reaction can be carried out in a polar aprotic solvent such as CH₂Cl₂Is carried out in (1).

Scheme B

The precursor sulfide (A) itself can be prepared in different ways, which are illustrated in schemes C, D, E, F, G, H and I.

In scheme C, formula (A)₁) Wherein L is a single bond, n is 1, R³H, and R¹、R²And Het is as defined above) may be prepared from the halide of formula (D) by nucleophilic substitution with a sodium salt of an alkyl thiol.

Scheme C

In scheme D, formula (A)₂) Wherein L is a single bond, n is 3, R³H, and R¹、R²And Het is as defined above) may be prepared from the chloride of formula (E) as follows: reacting the chloride of formula (E) with 2-monosubstituted methyl malonate in the presence of a base such as potassium tert-butoxide to give 2, 2-disubstituted malonate, hydrolyzing under basic conditions to form diacid, decarboxylating the diacid by heating to give monoacid, reducing the monoacid with borane-tetrahydrofuran complex to give alcohol, tosylating the alcohol with tosyl chloride (tossylchloride) in the presence of a base such as pyridine to give tosylate (tosilate), and then replacing the tosylate with the sodium salt of the desired thiol.

Scheme D

In scheme E, formula (A)₃) Wherein L is a single bond, n is 2, R³H, and R¹、R²And Het is as defined above), may be prepared from a nitrile of formula (F) as follows: deprotonation of the nitrile of formula (F) with a strong base and alkylation with an alkyl iodide gives an α -alkylated nitrile, hydrolysis of the α -alkylated nitrile in the presence of a strong acid such as HCl gives an acid, reduction of the acid with a borane-tetrahydrofuran complex gives an alcohol, tosylation of the alcohol with tosyl chloride in the presence of a base such as pyridine gives a tosylate, which is then replaced with the sodium salt of the desired thiol.

Scheme E

In scheme F, formula (A)₄) Sulfide of (2) (wherein n is 0, R)¹is-CH₂-, L is-CH (CH)₂)_P-, where p is 2 or 3, and R¹S and L together form a 5-or 6-membered ring, and Het is as described above) may be prepared from tetrahydrothiophene (p ═ 2) or thiahexacyclic (p ═ 3) (G). The desired sulfide (A) is obtained in satisfactory yields by chlorination of a cyclic sulfide starting material with N-chlorosuccinimide in benzene followed by alkylation with certain lithiated heterocycles or Grignard reagents₄)。

Scheme F

Obtaining the formula (A)₄) A more efficient scheme for cyclic sulfides of (a) is illustrated in scheme G, wherein Het is a 6-substituted pyridin-3-yl group and Z is as defined above. Accordingly, thiourea is added to a substituted chloromethylpyridine, hydrolyzed, and alkylated with the appropriate bromochloroalkane (p ═ 1, 2, or 3) under aqueous base conditions to give the sulfide (H). Subsequent cyclization of (H) in a polar aprotic solvent such as THF (tetrahydrofuran) in the presence of a base such as potassium tert-butoxide affords the cyclic sulfide (A)₄)。

Scheme G

Certain of the formula (A)₁) Wherein Het is substituted pyridin-3-yl, Z is as defined above, and R¹、R²＝CH₃) Alternatively can be prepared by the methods set forth in scheme H. Correspondingly, the appropriate enone is coupled with dimethylaminoacrylonitrile and then cyclized with ammonium acetate in DMF to give the corresponding 6-substituted pyridine-3-carbonitrile. It is treated with methylmagnesium bromide, reduced with sodium borohydride, chlorinated with thionyl chloride and then nucleophilic substituted with the sodium salt of an alkylthiol to give the desired sulfide (A)₁)。

Scheme H

A variation of scheme H is illustrated in scheme I, wherein an enamine is coupled to a substituted enone, followed by ammonium acetate at CH₃Cyclization in CN gives the desired sulfide (A)₁) The enamines are formed by the addition of amines, such as pyrrolidines, to Michael adducts (Michael adducts) of certain sulfides with appropriately substituted α, β -unsaturated aldehydes, where R is¹、R²、R³And Z is as defined above.

Scheme I

The oxidizing agent employed in the present invention is ruthenium tetroxide or an alkali metal permanganate.

Ruthenium tetroxide is a powerful oxidizing agent and is most suitably generated in situ using an alkali metal periodate in the presence of a water soluble ruthenium salt capable of being converted to ruthenium tetroxide. The water-soluble ruthenium salts need only be present in catalytic amounts, typically from 0.05 to 2.0 mol%, based on the amount of sulfilimine. Stoichiometric amounts of periodate are generally preferred, but it is generally convenient to employ 0.9 to 1.1 molar equivalents of periodate based on the amount of sulfilimine. Ruthenium salts that can be converted to ruthenium tetroxide include, but are not limited to, ruthenium dioxide and ruthenium chloride, with ruthenium chloride being preferred. Sodium periodate and potassium periodate are the preferred alkali metal periodates.

Sodium permanganate and potassium permanganate are the preferred alkali metal permanganates, with sodium permanganate being most preferred. The permanganate equivalents can range from 0.9 to 1.1 equivalents relative to the sulfilimine substrate. The preferred number of equivalents is 0.95. When post-treating the permanganate reaction mixture, it is advisable to quench the excess permanganate. Metabisulfites (such as sodium metabisulfite or potassium metabisulfite) may be used in the quenching step of the post-treatment. The preferred salt selected is the sodium salt. The number of equivalents of metabisulfite may be 1.0 to 5.0 relative to the stoichiometric amount of permanganate. The preferred range of equivalents is from 2.0 to 4.0.

The process of the invention is carried out in a suitable organic solvent which is substantially inert to the strong oxidation conditions of the reaction. Particularly suitable organic solvents are halogenated aliphatic and halogenated aromatic hydrocarbons such as dichloromethane, chloroform, 1, 2-dichloroethane and dichlorobenzene, and also aliphatic and aromatic nitriles such as acetonitrile and benzonitrile. Preferred reaction solvents are dichloromethane and acetonitrile. It is generally convenient to carry out the oxidation in a biphasic solvent system comprising, for example, a mixture of a halogenated aliphatic hydrocarbon such as methylene chloride and water.

The reaction temperature may range from-10 ℃ to 45 ℃. The preferred range is from 10 ℃ to 30 DEG C

The sulfilimine substrate may be dissolved in an organic solvent and then co-added to an aqueous solution of the oxidizing agent, or an aqueous solution of the oxidizing agent may be added to a solution of sulfilimine in an organic solvent. The preferred order of addition is to co-add the sulfilimine solution to the aqueous solution of the oxidizing agent.

The following examples are set forth to illustrate the invention.

Examples

EXAMPLE 1 preparation of (2-Chloropyridin-5-ylmethyl) (methyl) -N-cyanosulfoximine

(2-Chloropyridin-5-ylmethyl) -N-cyanothioimine (151g, 0.7mol) was dissolved in 4l of dichloromethane and then added to a solution of sodium periodate (302g, 1.4mol) in 3 l of water. Ruthenium (III) trichloride hydrate (160mg) was added, and the mixture was stirred at room temperature for 20 minutes. The organic phase is separated over MgSO₄Dried, treated with charcoal, then filtered and concentrated. The brown solid was triturated in a mixture of acetone and hexane, collected by filtration and then dried to give 110g of product, mp 120-.¹HNMR(300MHz，CDCl₃)δ8.5(d，1H，J＝1.9)，7.9(dd，1H，J＝1.9，8.3)，7.6(d，1H，J＝8.3)，5.1(s，2H)，3.45(s，3H)。

EXAMPLE 2 preparation of (1- (2-Chloropyridin-5-yl) -ethyl) (methyl) N-cyanosulfoximine

A solution of 300 grams of sodium periodate in 3.1 liters of water was prepared. 2 liters of carbon tetrachloride and 1.7 liters of acetonitrile were added to the solution, followed by the addition of 1.6 grams of ruthenium (III) trichloride hydrate. (1- (2-Chloropyridin-5-yl) -ethyl) N-cyanothioimine (161g, 0.7mol) was dissolved in 350 ml of acetonitrile and added to the stirred mixture at room temperature. After 20 minutes, the organic phase is separated and washed with NaHSO₃Washing with an aqueous solution over MgSO₄Dried, treated with charcoal, then filtered and concentrated. The solid obtained is triturated in a mixture of hexane and acetone to give 101g of a 3: 2 mixture of diastereomers as a white solid, mp 102-110 ℃.¹H NMR(300MHz，d₆-DMSO)δ8.5(d，1H)，8.0(m，1H)，7.6(d，1H)，5.2(m，1H)，3.45(m，3H)；1.8(d，3H)。

EXAMPLE 3 preparation of (2-chloro-3-nitropyridin-5-ylmethyl) (methyl) -N-cyanosulfoximine

The solution was prepared as follows: sodium periodate (661mg, 3.1mmol) was added to 7 ml of water at 25 ℃ followed by 7 ml of dichloromethane and then ruthenium (III) trichloride hydrate (8.7mg, 0.04 mmol). (2-chloro-3-nitropyridin-5-ylmethyl) -N-cyanothioimine (400mg, 1.5mmol) was dissolved in 3 ml of dichloromethane and then added dropwise to the solution at room temperature. After 20 minutes, the organic phase was separated, dried, filtered and concentrated. The residue was purified by column chromatography to give the product, mp 138-.¹H NMR(400MHz，CDCl₃/DMSO)δ8.44(d，1H)，8.31(d，1H)，4.82(s，2H)，3.04(s，3H)。LC-MS(ELSD)：C₈H₈ClN₄O₃Mass number calculation of S [ M + H ]]⁺275, observed value 275.

EXAMPLE 4 preparation of (2-chloro-3-methoxypyridin-5-ylmethyl) (methyl) -N-cyanosulfoximine

The solution was prepared as follows: sodium periodate (351mg, 1.6mmol) was added to 3 ml of water at 25 ℃, followed by 3 ml of dichloromethane and then ruthenium (III) trichloride hydrate (4.6mg, 0.021 mmol). (2-chloro-3-methoxypyridin-5-ylmethyl) -N-cyanothioimine (200mg, 0.82mmol) was dissolved in 2.5 ml of dichloromethane, added dropwise to the solution, and then stirred at room temperature for 30 minutes. Filtering, separating organic phase, and purifying with Na₂SO₄Dried, filtered and concentrated to give a white solid. mp 123-.¹H NMR(400MHz，CDCl₃)δ7.98(d，1H)，7.41(d，1H)，4.63(dd，1H)，3.99(s，3H)，3.11(s，3H)。LC-MS(ELSD)：C₉H₁₁C₁N₃O₂Mass number calculation of S [ M + H ]]⁺260, observation 260.

EXAMPLE 5 preparation of (2-chloro-3-bromopyridin-5-ylmethyl) (methyl) -N-cyanosulfoximine

The solution was prepared as follows: sodium periodate (246mg, 1.2mmol) was added to 3 ml of water at 25 ℃, followed by 3 ml of dichloromethane and then ruthenium (III) trichloride hydrate (6.6mg, 0.029 mmol). (2-chloro-3-bromopyridin-5-ylmethyl) -N-cyanothioimine (170mg, 0.6mmol) was dissolved in 2 ml of dichloromethane, added dropwise to the solution, and then stirred at room temperature for 1 hour. The organic phase is separated over MgSO₄Dried, filtered and concentrated to give a white solid, mp 139-.¹H NMR(400MHz，CDCl₃/DMSO)δ8.6(d，1H)，8.4(d，1H)，5.1(s，2H)，3.5(s，3H)。LC-MS(ELSD)：C₈H₇BrClN₃Calculation of the mass number of OS [ M + H]⁺308, observed value 308.

EXAMPLE 6 preparation of (2-methoxypyridin-5-ylmethyl) (methyl) -N-cyanosulfoximine

The solution was prepared as follows: sodium periodate (818mg, 3.8mmol) was added to 6 ml of water at 25 ℃ followed by 6 ml of dichloromethane and then ruthenium (III) trichloride hydrate (22mg, 0.095 mmol). (2-methoxypyridin-5-ylmethyl) -N-cyanothioimine (400mg, 1.9mmol) was dissolved in 2 ml of dichloromethane and then added dropwise to the solution. Reaction mixture with CH₂Cl₂Diluted (10 ml) and filtered through a pad of celite. The organic phase is separated over MgSO₄Dried, filtered and concentrated to give sulfoximine as a yellow solid, mp-89-91 ℃.¹H NMR(400MHz，CDCl₃/DMSO)δ8.2(d，1H)，7.7(dd，1H)，6.9(d，1H)，4.5(s，2H)，4.0(s，3H)，3.1(s，3H).LC-MS(ELSD)：C₉H₁₁N₃O₂Mass number calculation of S [ M + H ]]⁺225. The observation value 225.

Example 7 preparation of 3- [ (2-trifluoromethyl) pyridin-5-yl ] -N-cyano-pentan-sulfoximine

The solution was prepared as follows: sodium periodate (861mg, 4.07mmol) was added to 14 ml of water followed by 24 ml of dichloromethane and then ruthenium (III) trichloride hydrate (8mg, 0.04 mmol). Reacting 3- [ (2-trifluoromethyl) -pyridin-5-yl]-N-cyanothiolane sulfimine (1.00mg, 3.66mmol) was added to the solution. The solution was stirred at room temperature overnight. Isopropanol (0.5 ml) was added to the solution. The reaction mixture was filtered through a pad of celite. The organic phase is separated over MgSO₄Dried, filtered and concentrated to give the sulfoximine as an off-white solid (360mg, 34%).¹H NMR (400MHz, acetone-d₆) Δ 8.89 (overlapping doublet, 1H), 8.25(m, 1H), 7.9 (overlapping doublet, 1H), 4.4-3.9(m, 2H), 3.8-3.6(m, 3H), 3.0-2.5(m, 2H).

EXAMPLE 8 preparation of (1- (2-trifluoromethylpyridin-5-yl) -ethyl) (methyl) N-cyanosulfoximine

A four-necked 5-L round bottom flask equipped with a dropping funnel, reflux condenser, mechanical stirring device and thermowell was charged with 1472g (0.845mol) of a 15% w/w solution of sulfilimine in dichloromethane. The solution was cooled to 3 ℃ with stirring in an ice-water bath. 299g (0.845mol) of 0% w/w aqueous sodium permanganate solution were added dropwise to the solution over a period of 2h via a dropping funnel. The addition rate was controlled so that the internal temperature rose from 3 to 11 ℃ during the permanganate addition. The dropping funnel was rinsed with 80mL of water. The reaction mixture was then stirred for 1h with ice bath cooling. To this mixture was added over 1.5h a solution of 645g of sodium metabisulphite (3.38mol) in 1200mL of water. A defined exotherm was noted during the start of the addition of the metabisulphite solution (internal solution temperature rose from 3 ℃ to 30 ℃). An additional 250mL of water was added and the reaction mixture was then stirred for an additional 2h until all brown manganese by-product had corroded from the reaction vessel wall (etch). To this mixture was added 180mL of acetonitrile. 2L of the reaction mixture are filtered off with suction (flash filtration) through a coarse frit funnel and the filter cake is washed with 250mL of dichloromethane. The organic layer was then concentrated on a rotary evaporator. The remaining portion of the reaction mixture was filtered through the same frit funnel and the filter cake was washed with an additional 250mL of dichloromethane. The bottom organic layer was collected, added to another portion and concentrated on a rotary evaporator to yield 228g (97% of theory) of an off-white solid. LC assay of the crude material showed a purity of 96%.

EXAMPLE 9 preparation of (1- (2-trifluoromethylpyridin-5-yl) -ethyl) (methyl) N-cyanosulfoximine

In a 5L 4-necked round bottom flask, 400mL of methylene chloride, 400mL of water, and 320mL (1.25mol) of 40% NaMnO₄The aqueous solution was cooled to 13 ℃ under ice bath. For 1 hour³/₄To this rapidly stirred mixture was added dropwise (about 1.0mol) a solution of sulfilimine in 1000mL of dichloromethane (about 1560 g). During this time the ice bath temperature was lowered or raised to maintain the reaction temperature at 13-20 ℃. After stirring for 30 minutes at 15 ℃ a solution of 570g (3.0mol, 3 eq.) of sodium metabisulphite in 900mL of water was added over 1.5h with rapid stirring. An exotherm was evident, first of all a rapid temperature rise from 15 to 28 ℃. The mixture was stirred at room temperature (23 ℃) for 30 minutes and then filtered. The solids were washed with two filter cake volumes of dichloromethane. The clear two-phase mixture was transferred to a 4L separatory funnel and the bottom organics collected. The aqueous layer was re-extracted with 30mL of dichloromethane and the organics containing the first cut (first cut) were combined. The solution was concentrated in vacuo to give 275g of a white solid. The solid was air dried overnight in a fume hood to give 260g and finally dried in a vacuum oven at 40 ℃ to give 259g (93% wt) of a white solid. LC analysis showed a 30: 68 (area) ratio of the two isomers and an area purity of 97%.

EXAMPLE 10 preparation of (1- (2-trifluoromethylpyridin-5-yl) -ethyl) (methyl) N-cyanosulfoximine

A solution of sulfilimine (ca. 0.022mol) in acetonitrile (50mL) was cooled in an ice bath to5 ℃ is adopted. To the well stirred solution was added (8.0 g, 0.022mol)40 wt% NaMnO over 20 minutes₄. The reaction temperature rose to 24 ℃ during the addition. The resulting brown reaction slurry was stirred for 30 minutes and then cooled to 5 ℃. A30% by weight aqueous solution of sodium metabisulphite (29.8 g, 0.047mol) was added portionwise to the stirred reaction mixture over 20 minutes. The addition was exothermic and the temperature rose from 15 ℃ to 20 ℃ during the addition. The reaction mixture slurry thickened during the addition. Additional acetonitrile (5mL) and water (5mL) were added to facilitate mixing. The quenched reaction mixture was vacuum filtered through a medium sintered glass filter funnel. The collected gray solid was rinsed with acetonitrile (5 mL). The combined filtrate and washings were transferred to a separatory funnel, the phases were allowed to separate and the lower aqueous phase was removed. The upper organic phase was concentrated in vacuo and the isopropanol solvent (40 g) was driven off to give 5.2 g (83% weight recovery) of crude sulfoximine as a yellow solid. Recrystallization from isopropanol (4mL) gave 3.3 g (52%) of sulfoximine as a white solid. LC analysis showed two isomers in a 81: 19 (area) ratio and an area purity of 89%.

Claims (6)

1. A process for the preparation of an insecticidal sulfoximine (Ia),

wherein

Het represents:

x represents C₁-C₄A haloalkyl group;

y represents hydrogen;

n is an integer of 0 to 3;

l represents a single bond;

R¹is represented by C₁-C₄An alkyl group;

R²and R³Independently represent hydrogen or C₁-C₄An alkyl group;

the process comprises oxidizing a sulfilimine of formula (I) by:

contacting said sulfilimine with an alkali metal permanganate salt in a suitable organic solvent which is substantially inert to strong oxidation conditions at a temperature of-10 to 45 ℃

Wherein R is¹、R²、R³Het, L and n are as defined above.

2. The method of claim 1, wherein Het is (6-substituted) pyridin-3-yl, and wherein X is C₁-C₂Haloalkyl, and Y is hydrogen.

3. The method of claim 1, wherein the starting sulfilimine has the structure:

wherein

Het、R²And R³As defined in claim 1.

4. The method of claim 1, wherein the temperature is from 10 ℃ to 30 ℃.

5. The process of claim 1, wherein the organic solvent is a halogenated aliphatic or halogenated aromatic hydrocarbon, or an aliphatic or aromatic nitrile.

6. The process of claim 1, wherein the process is carried out in a biphasic solvent system comprising a mixture of a halogenated aliphatic hydrocarbon and water.