HU193036B - Herbicide compositions containing chloro-acetamide derivatives as active substances and process for preparing the active substances - Google Patents

Description

The present invention relates to herbicides containing thienyl and isothiazolyl derivatives containing N-substituted chloroacetylamino groups on one of the ring carbon atoms and to a process for their preparation.

Many herbicides containing N-substituted α-haloacetanilide are known.

U.S. Pat. No. 4,282,028 discloses N-substituted-N- (2,5-diacyl-1-pyrid-1-yl) -haloacetamides with herbicidal and plant growth regulating activity. U.S. Patent No. 3,749,775 discloses N-substituted N- (2-thiazolyl) chloroacetamides as active ingredients for insecticides and acaricides. Japanese Patent Application Laid-Open No. 78/86033 relates to herbicidal 3-acylaminoisoxazoles. U.S. Patent Application No. 65 04109 describes tetrahydrothiophene 1,1-dioxides with pest control activity. Increasingly effective herbicides are still needed. The novel 5-membered heteroaromatic compounds are particularly potent herbicides and have good soil resistance.

The present invention provides compounds of formula I; X and X ₂ are independently halogen,

C 1-4 alkyl, C 1-4 alkylthio, C 1-4 alkoxy, C 1-4 alkylsulfin 1, C 2-4 alkanoyl, C [= NO (C 1-4 alkyl) ] - (C 1 -C 3 alkyl), C [O (C 1 -C 4 alkyl)] ₂ - (C 1 -C 3 alkyl) or (C 1 -C 5 alkoxy) carbonyl; X and X ₂ may each be hydrogen;

Z is -NH- or ^> CZ, a group of formula -NH and Z, X, and X ₂ C 1-4 alkyl; Z, hydrogen, halogen, (C1-C4) -alkyl or ((C1-C4) -alkoxy) -carbonyl,

Y (a) C 1 -C 4 alkyl, C 3 -C 5 haloalkenyl, C 3 -C 5 alkynyl, C 1 -C 4 haloalkyl, or benzyl;

or (b) -CHfRJ-COY! and R, hydrogen or (C1-C4) -alkyl and Y, hydroxy, (C1-C4) -alkoxy, (C3-C5) -alkynyloxy, (C1-C4) -alkylamino, di ( (C 1 -C 4 alkyl) amino or -NH-N = C (C 1 -C 3 alkyl) ₂ or (c) -R ₂ -A ₂ , wherein R _{2 is} -CH ₂ - or -CH ₂ -CH ₂ - which is substituted with unsubstituted or C 1 -C 5 alkyl and is substituted with A ₂ 1 -pyrazolyl, 3,5-dimethyl-1-pyrazolyl, 1,2,4-triazolyl, 2 pyrimidinyl or furyl, thienyl, thiazolyl, isoxazolyl, 1,3,4-thiadiazolyl or tetrahydrofuryl optionally substituted with C 1-4 alkyl or optionally C 1-4 alkyl and / or Mono- or disubstituted with C 4 alkylthio

1,3,4-triazolyl or (d) -AOR ₃ , wherein R _{3 is} hydrogen or C 1 -C 4 alkyl which may be substituted by halogen, cyano or C 1 -C 4 alkoxy,

C 1-4 alkyl optionally substituted with C 1 -C 4 alkoxy, which may be attached to R _{3 to} form a 1,3-dioxolane ring, wherein the nitrogen and oxygen to which A is attached are separated by up to 3 carbon atoms; or (e) a group represented by the formula -j ₂ H-C = NOR _{4 5} r ' ₅ powder in which

R _{4 is C} 1-4 alkyl, R ₅ and R ₁₅ are each independently hydrogen or methyl.

The active ingredients of the herbicidal compositions according to the invention are those compounds of the formula I in which

Z xXZH;

X and X ₂ are each C 1 -C 4 alkyl or

One of X and X ₂ is C 1 -C 4 alkyl and the other is C 1 -C 4 alkoxy or -C (= NOCH ₃ ) CH _3; and

Y is di (C 1 -C 4 alkyl) aminocarbonyl, C 1 -C 4 alkoxy, 1-pyrazolyl, 3,5-dimethyl-1-pyrazolyl, or

C 1-4 alkyl or C 2-5 alkynyl substituted with 2- (C 1-4 alkyl) -1,3,4-triazol-4-yl.

When Y, R _{3 is} halogen, the halogen is preferably chlorine or bromine; any of the groups thus substituted is primarily monosubstituted. When Y is a halogen-substituted group, the halogen is usually not in the 1-position when it is used as an herbicidal agent (such 1-halogenated compounds are generally unstable; however, they are useful as intermediates for the preparation of compounds of formula Y is alkoxyalkyl or pyrazolylmethyl);

Y is a suitable example of a 2-chloroethyl group.

-2193036

When R 1 is C 1-4 alkyl, preferably methyl or ethyl, especially methyl.

When R _{2 is} methylene, it may be substituted by one or two, preferably one C 1 -C 5, alkyl groups. When R _{2 is} ethylene, it may be substituted with up to four C 1 -C 5 alkyl groups and preferably mono- or disubstituted. When the ethylene group is disubstituted, the substituents are preferably on different carbon atoms.

Preferred C 1 -C 5 alkyl substituents on R _{2 are} methyl and ethyl, especially methyl. When R _{2 is} substituted with C 1-5 alkyl, it is preferably monosubstituted. In particular R ₂ is methylene or -CH _(CH3) group.

When A ₂ is a 5-membered heterocycle as defined above which is attached to R _{2 by a} ring carbon, this ring is, for example, substituted or unsubstituted furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, 1,2, 4 or 1,3,4-oxadiazolyl or 1,3,4-triazolyl; examples of these definitions include 2-furyl, 2-thienyl, 2-methyl-4-thiazolyl, 3-methyl-5-isoxazolyl, 2-ethyl-1,3,4-oxadiazol-5-yl, , 3-methyl-1,2,4-oxadiazol-5-yl, 1-methyl-2-methylthio-1,3,4-triazol-5-yl, and 2-methyl-1,3,4 triazol-5-yl.

The group -AOR ₃ is suitably represented when attached to the AR _{3 to} form a ring, for example 1,3-dioxolan-4-yl- (C 1 -C 3 alkylene) -, 1,3-dioxolan-2-yl- C 1-3 alkylene).

A may be substituted or unsubstituted and substituted with C 1 -C 4 alkoxy. The substituted A group is preferably monosubstituted.

According to the present invention, the compounds of formula I are prepared by the following processes:

a) in the compound of formula II, X, X ₂ , Z and Y are as defined above, the hydroxy group of the N-hydroxyacetyl group being replaced by chlorine; obsession

b) (III), a compound of formula X ,, X ₂ and Z are as defined above - compound (IV) of the formula - Y lehasíth'ató under the reaction conditions defined above, and L N-alkylation group - are reacted; obsession

c) for the preparation of compounds of formula Ia in the formula

R 'is hydrogen or C1-C3 alkyl,

Y ₂ is a group A, -OR ₃ , or -N (CH ₃ ) COCH ₃ ,

A di- or triazole ring attached to one of its nitrogen atoms by -CHR ';

(VI) compound - - defined _Y2 above - a reactive derivative of X ,, X _2, and Z and R ₃ compound defined in the formula (V) wherein - X ,, X ₂ and Z and R 'are as previously defined reacted; obsession

d) N-acetylating the compound of formula VII: X, X ₂ and Z, Y as defined above with chloroacetyl chloride or a reactive functional derivative thereof.

Process (a) of the present invention can be carried out in conventional manner to replace a hydroxy group with chlorine under known conditions.

Such substitution may be accomplished, for example, by treating a compound of formula II with a chlorinating agent such as thionyl chloride under known conditions of analogous reactions.

In one variant of the chlorination process, the compound of formula (II) is first converted to the corresponding sulfonyloxy derivative, for example by O-sulfonation with a sulfonyl halide, and then the sulfonyloxy derivative is converted to the desired sulfonyloxy compound. by nucleophilic substitution of chloro.

The chloride anion providing reagent for nucleophilic substitution is, for example, an alkali metal chloride such as sodium chloride, quaternary tetrabutylammonium chloride or 4-dimethylaminopyridine hydrochloride. The substitution may conveniently be carried out in dichloromethane or an aqueous-organic two-phase system; the organic phase is, for example, a hydrocarbon such as toluene, and a suitable phase transfer catalyst is employed and is heated at 40-120 ° C, for example.

Process b) can be carried out in conventional manner for N-alkylation of amides under known conditions. The reaction is preferably carried out under a reaction inert solvent such as dimethoxyethane or acetonitrile or an aqueous-organic biphasic system in the presence of a phase transfer catalyst.

Suitably, in formula (IV), L is a sulfonyloxy group of chlorine, bromine or organic sulfonic acid, such as mesyloxy or p-tosyloxy.

The compounds of formula (III) are preferably used in salt form, in particular as the alkali metal salt, for example the sodium salt. Salts are prepared in conventional manner by reacting a compound of formula (III) with a base such as an alkali metal amide, anhydride, a hydroxide or an alcohol.

For the preparation of the compounds of formula (Ia) according to process (c), the compounds of formula (V) are suitably used in the form of an alkali metal salt, for example the sodium salt. When Y _{2 is a} di- or triazole group, the compound of formula (V) may also be used in the form of an N-trialkylsilyl compound such as N-trimethylsilyl. The reaction is carried out in a conventional manner.

The reaction of process d) may also be carried out in conventional manner for N-chloroacetylation of amines under known conditions. When chloroacetyl chloride is used as the N-chloroacetylating agent, the reaction is conveniently

-3193036 in the presence of a binding agent such as potassium carbonate.

The compounds of formula (I) may be isolated from the reaction mixture for their preparation by conventional methods.

Here, it will be appreciated that the conversion of one compound to another compound of the present invention, for example, an acid group to an ester group, a carbonyl group to an oxime group, a haloalkyl group to an ether group (or vice versa), and the like. can be accomplished by conventional methods. It may also be stated that the compounds of the present invention may have one or more asymmetric centers and may accordingly exist in optically active, diastereomeric, racemic or geometric isomeric forms. In general, the compounds are used as herbicidal active ingredients in the form of mixtures thereof, although separation can be carried out in a known manner.

The compounds of formula (II), (III), (V) and (VII) are novel and form part of the invention.

The carboxylic acid ester of the compound of formula (II) - X, X ₂ and Z as defined above - can be prepared by the ammonolysis year and then by introducing the Y group as defined above by N-alkylation into the compound of formula (VIII). . Said esters may be prepared by reacting the corresponding compounds of formula IX with the corresponding ester of hydroxyacetyl chloride, such as acetacetic acid chloride, as described above.

Compounds of formula (III) may also be prepared by reacting compounds of formula (IX) with chloroacetyl chloride.

Compounds of formula (V), which are in fact a subset of compounds of formula (I), can be prepared by reacting a compound of formula (IX) with a suitable aldehyde and then reacting the resulting Schiff base with chloroacetyl chloride.

Compounds of formula (IX) may be N-alkylated to form compounds of formula (VII). Alkylation may be carried out in conventional manner with suitable alkylating agents, for example halides, or suitably reductively over a Schiff base or over a period of time.

Most of the compounds of formula IX are novel.

They form a valuable group of new compounds of formula IX at the 2- and 4-positions

3-Aminothiophenes (Compounds of Formula IXa) substituted with C 1-4 alkyl and / or C 1-4 alkoxy. Compounds of formula IXa are also within the scope of the present invention.

Compounds of formula (IX) may be prepared by reduction of the corresponding nitro compounds, for example by catalytic hydrogenation in hydrogen in the presence of palladium. Compounds of formula IXa having a methyl group at the 2- or 4-position may be prepared by reduction of the corresponding thiophenecarboxylate with a complex hydride, such as sodium hist (methoxyethoxy) aluminum hydride. Where appropriate, the compounds of formula IXa may be prepared from the corresponding carbamate esters, such as benzyl carbamate, by hydrolysis. The carbamates used as starting materials, for example, can be prepared from the corresponding acid via its azide followed by the Curtius-r reaction.

Starting compounds, the preparation of which is not described herein, are known or can be prepared and purified in a manner analogous to that described or known in the art.

The compounds of formula I inhibit or modify the development of plants and can therefore be used as active ingredients in herbicides. Plants include germinating seeds, shoots and mature plants, including underground parts.

Thus, the compounds of the present invention can be used as active ingredients of herbicides, as mentioned above, in an application rate of 1.4 to 5.6 kg / ha for monocotyledonous and dicotyledonous plants such as Lepidium sativum, Avena sativa, Agrostis alba and Lolium perenne. damage from pre-emergence or post-emergence experimental treatments. Due to their herbicidal activity, the active compounds of the invention can be used to control dicotyledonous and needle-like weeds. The herbicidal activity was further investigated by the application of selected active substances at application rates of 0.2-5.0 kg / ha of active substance, for example 0.2, 1.0 and 5.0 kg of active substance per hectare on dicotyledonous weeds such as Amaranthus retroflexus, Capsella bursa-pastoris, Chenopodium album, Stellaria media, Senecio vulgaris and Galium aparine plants, and especially needle-like weeds such as Agropyron repens, Agrostis alba, Alopecurus myosuroides, Apera spica-venti, Avena fatua, Echinochloa crus-galli, Bromus t. halepense, Digitaria spp. and Setaria spp. plants.

The active compounds of the present invention are relatively less harmful to crop plants than to weeds. Selective herbicidal efficacy has been found in, for example, corn, soy, cotton, sugar beet, potato, alfalfa, sunflower, rape, peanut and flax-4193036, for example, depending on the active ingredient used and its application rate. Thus, the compounds of the present invention can also be used as active selective herbicides in crop plantations.

The amount of active ingredient required to achieve the desired effect for general herbicidal and selective herbicidal activity may vary depending on the crop to be treated, where selective herbicidal activity is required, and other constant factors such as the active ingredient, mode of application, treatment conditions and the like. Suitable application dosages may be determined by routine assays or by comparing the active compounds of the present invention to those of known application rates, for example, in greenhouse studies. Generally, satisfactory results can be obtained when the active compound is applied in a dosage of about 0.1 to 5 kg / ha, preferably about 0.2 to 4 kg / ha, particularly preferably 0.5 to 3.0 kg / ha, and the treatment is applied as necessary. repeat. When applied in crop plantations, the application rate should preferably not exceed 3 kg / ha.

For practical use, the compounds of formula I, together with agriculturally acceptable diluents, are processed into herbicides. Suitable agents contain from 0.01% to 99% by weight of active ingredient, from 0% to 20% by weight of a plant physiologically acceptable surfactant and from 1 to 99.99% by weight of a solid or liquid diluent. Higher levels of surfactant additive relative to the active ingredient may be desirable in some cases and may be accomplished by addition to the agent or by tank mixing. The compositions generally contain from 0.01% to 25% by weight of the active ingredient in a formulation for immediate use. Of course, the active ingredient may be present in smaller or greater amounts depending on the intended use and the physical properties of the active ingredient. Concentrated agents to be diluted before use generally contain from 2% to 90%, preferably from 10% to 80%, by weight of the active ingredient.

Agents containing the active compounds of the present invention may conveniently be in the form of powders, granules, granules, suspension concentrates, wettable powders, emulsifiable concentrates and the like. The agents may be prepared in conventional manner, for example, by mixing the active compounds with diluents or diluents. More particularly, liquid agents can be prepared by mixing the ingredients, finely divided solids by mixing and usually milling, suspensions by wet milling, granulates and granules by impregnating or coating granular carriers or by agglomeration.

The active compounds of the present invention may also be processed into microencapsulated forms.

Plant-physiologically acceptable additives may also be added to the agents to enhance the efficacy of the active ingredient, to prevent foaming, adhesion and corrosion.

As used herein, a surfactant additive is defined as a plant physiologically acceptable material that produces emulsifiability, sprayability, wettability, dispersibility or other surface modifying properties. Exemplary surfactants include sodium lignin sulfonate and lauryl sulfate.

A diluent as used herein is a solid or liquid plant physiologically acceptable material which is capable of diluting the concentrated material to a concentration that may be used or desired. For powders and granules, for example, talc, kaolin or diatomaceous earth; for liquid concentrates, for example, hydrocarbons, such as xylene or alcohol, such as isopropanol, and for liquid, directly applicable agents, include water or gas oil.

The agents of the invention may also contain other biologically active agents, such as similar or complementary herbicides or antidoting, antifungal or insecticidal agents.

The following examples illustrate the composition of herbicides.

Example A)

Wettable powder

25.sz. The active ingredient is mixed with 25 tr of artificial powdered silica, 2 tr of sodium lauryl sulfate, 3 tr of sodium lignin sulfonate and 45 tr of finely divided kaolin and milled until the average particle size is 5 microns. The resulting wettable powder is diluted with water to the desired concentration of the spray liquid before use.

Example B)

Emulsion Concentrate tr 25 The active ingredient is thoroughly mixed with 40 tr of xylene, 30 tr of dimethylformamide and 10 tr of emulsifier (e.g., Atlox4851 B, a mixture of calcium alkylarylsulfonate and polyethoxylated triglyceride; Atlas Chemie GmbH) until a homogeneous solution is obtained. The resulting emulsion concentrate is diluted with water before use.

Example C)

Granules kg 25.tr. The active ingredient is dissolved in 25 ml of methylene chloride. To the solution is added 95 kg of granular attapulgite (24/48 mesh / inch mesh) and mixed thoroughly. The solvent was then evaporated under reduced pressure.

Example D)

An emulsifiable concentrate of the active ingredient tr (I), such as 2-chloro-N - [(1-methyl-2-methoxy) ethyl] -N- (2,4-dimethylthien-3-yl) acetamide, The tr emulsifier (a mixture of calcium alkylaryl sulfonate, polyethoxylated nonylphenol and polyethoxylated triglyceride) and 4 tr xylene are thoroughly mixed until a homogeneous solution is obtained. The resulting emulsifiable concentrate was diluted with water before use.

The process of the present invention is illustrated by the following examples; Rf values were determined on silica gel, unless otherwise by _one.

end products

Example 1

N- (2,4-Dimethylthien-3-yl) -N- (1,3-dioxolan-2-ylmethyl) chloroacetamide (process a)

1.7 g (0.0063 mol) of N- (2,4-dimethylthien-3-yl) -N- (1,3-dioxolan-2-ylmethyl) bridge roxyacetamide, 58 mg of benzyl To a thoroughly stirred mixture of triethylammonium chloride, ml of toluene and 7 ml of 30% sodium hydroxide solution was added dropwise, without cooling, 1.31 g (0.0069 mol) of p-toluenesulfonyl chloride in 3.5 ml of toluene. solution. After the exothermic reaction, the ^reaction: mixture was stirred at room temperature for 20 hours.

The toluene layer was separated, washed with water and dried over anhydrous sodium sulfate.

The solvent was removed on a rotary evaporator and the crude residue was recrystallized from diethyl ether to give N- (2,4-dimethylthien-3-yl) -Ν- (1,3-dioxolan-2-ylmethyl) tosyloxy acetamide ("tosylate") is obtained; mp 101-103 ° C.

A mixture of the above tosylate (2.16 g, 0.0051 mol), tetrabutylammonium chloride (1.84 g, 0.0066 mol), water (16 ml) and toluene (16 ml) was heated at 90 ° C for 6 hours with stirring. The toluene layer was then separated, dried over sodium sulfate and concentrated in vacuo.

The residue was chromatographed on a silica gel column. Hexane: ethyl acetate (2: 1); elution with an acetate mixture afforded the title compound as analytically pure crystals; mp 76-78 ° C.

Example 2!

N- (2,4-Dimethyl-thien-3-yl) -N-methoxy-ethyl-chloro-acetamide (process a)

2.0 g (0.008 mol) of N- (2,4-dimethylthien-3-yl) -N-methoxyethylhydroxyacetamide and 0.92 g (0.008 mol) of 4-dimethylaminopyridine To a solution of (DMAP) in anhydrous methylene chloride was added a solution of 0.93 g (0.008 mol) of mesyl chloride in 20 ml of anhydrous dichloromethane without stirring.

The mixture of DMAP hydrochloride and the methanesulfonate of the starting compound was refluxed for 25 hours and then concentrated in vacuo.

The resulting oil solidified after column chromatography on silica gel (elution with diethyl ether) by cooling to -20 ° C. 54-55 ° C.

Example 3

N- (Chloroacetyl) -N- (2-carbomethoxy-4-methylthien-3-yl) alanine ethyl ester (method b) to 1.5 g (0.05 mol) of sodium hydride (80) To a vigorously stirred suspension of a% dispersion in mineral oil (250 ml) was added dimethyloxyethane (9.9 g, 0.04 mol) in solid N- (2-carbomethoxy-4-methylthien-3-yl) chloroacetamide.

After the addition, the resulting solution of the sodium salt was stirred for an additional hour at 50 ° C and then allowed to warm to room temperature and treated with a solution of 7.25 g (0.04 mol) of 2-ethyl bromopropionate in 50 ml of anhydrous dimethoxyethane. .

After 4 hours at 50 ° C, the reaction mixture is filtered and concentrated in vacuo (50 ° C / 3 Pa). The resulting brown oil was chromatographed on silica gel (eluent: diethyl ether: hexane = 2: 1, v / v) to give the title compound in analytically pure form. 135 DEG C. at 0.65 Pa.

Example 4

N- (1H-Pyrazol-1-ylmethyl) -N- (2,4-dimethylthien-3-yl) chloroacetamide (Method b)

19.35 g (0.095 mol) of N- (2,4-dimethylthien-3-yl) chloroacetamide, 4.15 g (0.01 mol) of benzyldimethylhexadecylammonium chloride, To a stirred mixture of g (1 mol) of sodium hydroxide, 200 ml of methylene chloride and 40 ml of water was added 17 g (0.11 mol) of solid 1-chloromethylpyrazole hydrochloride at such a rate that the temperature did not rise to 25 ° C. over.

After the addition, the reaction mixture was further stirred

After stirring for 2.5 hours at room temperature, water (100 ml) was added. The organic layer was separated, washed three times with 200-200 mL of water, dried over sodium sulfate and evaporated to dryness. The residue was chromatographed on a silica gel column. Elution with hexane / diethyl ether (1: 1 v / v) gave the title compound as an analytically pure syrup which crystallized overnight at -20 ° C; mp 88-89 ° C. (recrystallized from diethyl ether).

-6193036

Example 5

Procedure N- [1- (1H-Pyrazol-1-yl) ethyl] -N- (2,4-dimethylthien-3-yl) chloroacetamide (c)

A solution of 12.7 g (0.1 mol) of 2,4-dimethyl-3-aminothiophene in 100 ml of anhydrous benzene containing 16 g of molecular sieve (3A) and two drops of concentrated sulfuric acid was added dropwise with stirring to a solution of 15 mol) of acetaldehyde so that the temperature of the mixture does not exceed 25 ° C.

After adding all the acetaldehyde, the reaction mixture was stirred for an additional 24 hours at room temperature and then filtered. Removal of the solvent gave the Schiff base as a light brown liquid.

To a solution of the above material (g) (0.085 mol) in dry toluene (75 ml) was added dropwise chloroacetyl chloride (9.7 g, 0.086 mol) at -30 ° C.

After the addition, the reaction mixture was stirred for an additional 30 minutes at -30 ° C and 12 g (0.085 mol) of 1-trimethylsilylpyrazole were added dropwise at this temperature. After the addition, the cooling bath containing the mixture of solid carbon dioxide and acetone was removed, the reaction mixture was allowed to warm to room temperature and stirred for an additional 20 hours.

The reaction mixture was then filtered and concentrated in vacuo. The syrup-like residue was chromatographed on a silica gel column. Elution with hexane / diethyl ether (3: 2 v / v) gave the title compound as colorless crystals, m.p. 76-78 ° C by recrystallization from diethyl ether.

Example 6

N- (4-Methoxy-2-methyl-thien-3-yl) -N- ^f (2-ethoxyethyl) choroacetamide (d / procedure)

6.05 g (0.03 mol) of N- (2-ethoxyethyl) -4-methoxy-2-methylthiophen-3-amine, 4.15 g (0.03 mol) of potassium carbonate in 10 ml A solution of 3.4 g (0.03 mol) of chloroacetyl chloride in 10 ml of methylene chloride is added dropwise to a well-stirred mixture of water and 100 ml of methylene chloride without cooling. After the exotherm (27 ° C) subsided, the mixture was stirred for an additional hour at room temperature.

The methylene chloride layer was then separated, washed twice with 100 ml of water, dried over sodium sulfate and concentrated in vacuo. The title crude residue obtained is arialitically pure; Rf = 0.23 (1: 2 hexane: diethyl ether).

A small amount of the material is distilled in a ball-cooler; b.p. 168-170 ° C at 6.5 Pa.

The compounds of formula (I) containing the substituents listed in Table 1 below are prepared in a manner analogous to that described in Examples 1-6 above. (Aryl represents X and X ₂ substituted thienyl and isothiazolyl groups).

-7193036 let sor- Arii Y Identification data

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Ul r-t • H r. B E • H • H U) ε I r-l 1-1 She CM <-t Φ · Η ul r-1 Γ 1 1 1 Φ Γ 1 * She She N • H t-L 6 C Φ rl rt rt Τ- Τ- E i-l 0 N N LAKE Τ- c • H -1 I · Η «—I l C -rt -rt i-l Ι Ι Γ • H N LAKE LAKE Ή Ι • H i-1 ul • H r-t CU · Η O g O • H r-l i-l r-1 1 LAKE • H • H H i-l x ex Ή Φ U • Η O Ul i-l good β ε ul She SHE H m »H X ul ♦ H • H She ul ε Φ q u φ • H rt <0 Ϊ0 1-1 Φ N N 1 1 • H LAKE 1 U < q u Φ while ex ε q σ3 Λ 43 · Η | LAKE LAKE tendon i-l LAKE X • H <r Φ Φ ex | rh X5 1 1 0 A3 M rt ul Z "\ U Ή 1 0 X 0 u> e ε CU 1 u • H Ϊ-1 U CM r-l ό 1 ° 3! Β 33 03 i-1 • H U i-l i-l N She I 1 CM 1 ί-l r-1 0 CM She 1-t q • r-l cu 1 · Η u • rt A! THE! ANCESTOR • H cu ul i-l • H She LAKE 1 <t r <r • H Ή ui 1 □ r-1 • H 0 q Ji! rH C cu X 1 1 Γ ί H | 1 • H U) N X <r K Τ- l r-1 ul ul ex Γ-I r-l • H • H ul Xi She 1 'H 0 Js! O r-l (—t O rí She i-1 <r ul Φ LAKE SHE ·> CM CO Ι 0 -M • H Φ Φ 1 · Ι-1 M- r-l r-1 Φ u , Ώ -rl Ul Jl CU · Η · Η 1 · Η N • H r. Φ £ Ή N co ·> * X • H • H ul 1 1 X CM • H Ul • H r-l rh £ cd u X Φ U • rl o ui cu iE3 i-i LAKE ul CM 6 Γ ul • H »1 Τ- 1- <r ul ul φ • H • H • H 1 C Φ U qj cU Γ cU ο ε n> X U Φ o 33 O U Φ r r i-1 | 1 Ί- Ι 1 1 1 Φ ε X X CU i-1 χ ε ul 1 1 • H 1 * CU-H She CU 6 U Z N • H ε r- i-1 • H r-1 i-l 1 t-L 1-I i-l r> £ 1 0 0 SHE • H CU Ή rH 1 u ε X »H 1 0 Τ3 1 u> Ο Ή cu O TO ex Ή 1 Ή c Ή • H i-l • H Ή Ή • H Γ • H ul Ul X ι-1 U) 0 X Ή CM '0 Ό 0 X • H U t Z-S Φ N XJ O CJ u 1 Ό X U Φ ul U) • H ul U> ul ul 1-I X Φ Φ Ή i was CU • H Φ u 1 N * i-1 U Λ 0 X exή ε • H | N eí'H i-l 1 τ- . q Ή Φ Φ ul Φ Φ Φ Φ Ή She s ε χ • H SHE r-i e ex q CM rd u ul She O X s Z 'H. X CU m M- ul e e Φ P e s 1 ul 1 1 Φ ul N I-1 1 1 * Φ e> 1 1 CU Φ ul N 0 1 1 * 1 o 1. | »< 1 1 1 1 1 1 Γ Γ Γ Γ m 0) - ε Φ • H cIJ CM CM XJ CM CM CM ε Φ • Η 1 τ- z z 1 · - co CM CM CM co m co m co co 1

1-1 i-1 H t-L r-1 I-1 i-l l H i-l ί-1 r-l r-l i-l t-1 r-l r-l X X X X X X X X X X X X X X X X X • H 1 • H • H | • H | • r4 1 • H • c4 | • r-1 • rM • H • H I «Η • H • l-l • H 1 • H • H • H • H »H • H • H Ή • H • H 1 • H • H Ή • H • H • H • H • H • H CO CO co co co CO CO co CO CO CO co CO CO 1 CO C0 CO co CO CO CO CO CO CO CO CO CO CO CO co CO co CO CO i-l i-l i-l 1 1 | 1 | 1 1 1 ! 1 i 1 | 1 | 1 1 1 1 1 | 1 | 1 1 1 | 1 1 | | 1 | 1 Ή Ή • H q q q q q c q q q q q q C q q q ¢ 3 c C3 q q q q q q q C3 c ¢ 3 q q C3 c q 1 1 1 φ φ φ φ Φ Φ Φ Φ Φ Φ φ Φ Φ φ Φ Φ Φ Φ Φ φ φ Φ φ Φ φ Φ Φ Φ Φ φ φ Φ Φ Φ co co co Ή • H • H • H • H • H Ή • H • H Ή • H • H • H • H »H Ή • H Ή • H • H »H • H • H Ή Ή • H • H Ή • H • H • H • H • H Ή 1 1 1 U> ul ul ul ul ul U> ul ul ul u) ul ul ul ul u> ui ul ul NEW ul ul ul ul ul ul NEW ul ul ul U> ul NEW NEW q e c 1 I 1 I 1 1 1 1 1 1 1 | 1 1 1 | 1 1 1 1 1 1 1 1 1 1 1 1 | 1 1 1 1 1 φ φ Φ 1-1 i-l 1-1 ί-1 1-1 1-1 l-1 i-l i-1 i-l 1-1 i-l i-l i-l T l -1 1-1 X i-1 X X r-l X X X X X X X i-1 rh i-l X X • Η Ή • H Ή • H • H Ή • H Ή • H Ή Ή • H • H • H • H • H • H • H • H • H • H Ή • H Ή <  Ή • H • H • H • H Ή Ή Ή Ή • H • H • H Ul U> ul U> U » U> u> U> ul U> U » ul U » ul ul ul ui ul ul ul NEW NEW U> NEW ul ul U> NEW U » ul ul NEW ul NEW U> ul U » 1. 1 1 Φ Φ Φ Φ <1) Φ Φ Φ <L) Φ Φ Φ Φ Φ CD Φ Φ Φ <L) Φ Φ fl) <1) <1) Φ (1) Φ Cl) ci) 0) <1) Φ <1> Cl) i-l i-1 1-1 B you e E E s E B s B B B B B B 6 B B s B B 6 B E B the s ε B B B Θ B B Ή Ή • H • H • H • H H • H Ή »H • i-l • H Ή • H Ή • H • H • H Ή Ή • H Ή • H Ή • H • H • H Ή Ή Ή • H Ή • H Ή • H Ul Ul ul X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X X φ Φ Φ 1 1 1 1 1 1 1 | 1 | 1 1 1 1 1 j 1 | | 1 f 1 1 1 1 | | 1 | 1 1 1 B <r <r <r -J <r <r <r <r <r <t <r <J · <f < <T <r <t <r <t <t <t <r CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM CM

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The compound is Arii Y Identification number

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c 'Ϊθ 'φ Ρ 'Φ 'φ 'flj α Ρ Ρ Ρ Φ X X X '03 Ρ φ φ Ρ φ Φ 0) X 0 α α Φ J2 03 , - Φ Η CO φ Φ - Χχ » CL «0 42 I » Φ Ρ Ρ Φ u CL \ " m ί-ι «-Ι 1 φ Φ Φ CL γω 3) Ρ ο • Ρ • Η ιΡ CL Ρ Ρ Π3 w p σ> Φ ο Ρ Ρ • Ρ 'Φ 'Φ m CL * <3 Ό * Ρ * Φ Φ Ρ ιθ 1 1 She α- ι γω 'φ Ο Χχ. • Χχ » φ CN Γ-4 ι- ' i £> ΓΩ *** " · - · 1 χ. C q Χχ » Χχ. • Ρ • Ρ She cn · ρ U γΡ υ 'Φ * Φ C U Ρ Ρ She * O q * P ο • Ρ 0 X X 'φ 0 φ Φ CN oo She u o o 00 4- She ο α ί- φ Ο Ο ο Ρ 00 Ο φ φ Ο Ο Ο X 4 Ο ο • Ρ • Ρ ω 4 CN She She & 0 CN * " 0 0 0 ***. »P m ο ο Φ ο X 42 * 1 3 0 Φ 4 0 0 Ό Ό 0 CN στ She rx She o u m c r- »m υ χ τ- 00 4 • Ρ Ί- 4 χζ 00 σ \ Ο 42 »- Ο 4 \ -ζ Χ, ζ m m m CN Γ * oo © *> 1 tn m <n She I r * \ Ο X | \ Ο Γχ m Γχ Χ- ' 1 m η \ 0 - r. σ> ο 1 I l m She 1 1 1 Ο Ό 00 | 1 Ζ Γχ 1 * - γω 1 1 1 CN I I Γχ Γχ I 1 00 00 σ> * - · »- CO in «4 · - γω 4 salt <Ν στ 1- σ> γω CN ο Γχ 00 4 4 σ> γω 4 4 ΓΩ She • 4 <O sD «- II 4 in Τ— · * r χ τ- m · » Γχ m \ Ο » 4 m ν> e \ Ο II 11 & CN ο ο ο Ο Ο η Ο • • • II • • II II • • • II • • II II • » CL Cl Cl S Cu the. CL CL 0- <Ρ ο. CL CLM-I CL CLM-i ιρ cl CL CL Μ-ι CL 0 CX Ιρ ιρ α Λ ftNÖ CL Cl Cl She O <4-1 C <P 0 o o U. □ £ lp Ο Ο di lp Ο ού od 0 Ο Ο CTI Ρ Ο Ο Ωύ 0d ο q c SHE O ip

P P 'P • Ρ Ρ Φ Φ ο Ρ P w φ p 1 1 Φ Ε 1 Μ ο 1-1 Φ -1 ι — Ι r — 4 Φ • P 1 Φ CN ι— <1 τ-1 Γ ΖΧ * 1 32 «Ο • Ρ | • Ρ • Ρ · Ρ • r ^ β P r- ε 1 «Ρ ζ-χ • Ρ ζχ • Ρ (Μ <Λ X '1 Ρ • Ρ Ρ Ρ Ρ AJ 1 P 4-r φ · Ρ · Ρ C 1 'Ρ Ρ ♦ Ρ X υ α 33 Ρ Ζ-4 fA Φ X φ φ φ Φ rP 1 - t • P iP • P 1 ρ X φ CN X φ X Ο «ο ο Ο Ο λ X Ρ C Ρ β β β | • Ρ 'P P 'P tP ex Ζ-Χ φ 1 Ρ 1 Ο | ο Ρ »° -Γ 2 Ο Ο 32 ' 0 Γ Ρ 1 1 ' Γ 1 1 p.m. φ P • P 0 · Ρ »P • ρ ε * - □ C UI • Ρ Ρ Φ Μ II II ζ Ζ Ο 0 rP Φ ι-4 • Ρ 1-4 1-4 τ — 4 ι — Ι CN φ γΊ P Si P P P • P χ Γ * <Ρ Φ φ X φ 1 U Ο ζχ ΖΧ II II - · ρ Γ- • Ρ Γ-1 β • Ρ Η-ι Ρ • Ρ 'Ρ ι-4 • Ρ «Ρ 1 1 • P r ε Φ ex φ P 0 4- 4- 0 1 Ο I Ο: ο Ο Λ «Λ 33 X Ζ X • Ρ | • Ρ 1 1 «Ρ φ 1 1 • Ρ Ρ 1 C -p P • ρ Γ 1 1 1 Φ CL 1 1 Ρ 0 Ρ Ρ • Ρ C ζ Ζ 32 31 ο Ο 1 ο Ρ 4- Ρ CN Ρ I 4-4 4J Φ Τ- • P X Φ X · Ρ • P 'P' P | Ο * ρ · ρ X X Ό φ X Φ II II ο Ο yX ζΧ ΖΧ y-S. φ | Φ 1 1 φ • Ρ 1 1 Φ Ι I X O e O X X X X »P ρ X X • Ρ Ο 1-4 β ο • Ρ 32 W > -ζ Λ <** fii ¹ Λ Ρ 1-1 β r-1 ι-ι β X 1 "4 1" ^ g • Ρ ι — 4 • P P Γ CL O 0 0 0 X 3 0 0 JC 'Ρ 44 • Ρ Ρ Ü Ο ο ο Ο 32 X X X Γ 0 1 > Ρ 0 Γ ο 0 0 Γ X 0 β X • P O P P P P SHE 1 ρ ρ φ T3 1 * q φ 1 I 1 1 1 Ο 0 0 ο • Ρ Ν • ρ Ρ Ν • Ρ Ρ Ν Ν • ρ Ο Ν • Ρ · Ρ X P 3 Φ φ Φ P q φ φ Ρ ί <Ν 1 Ρ CN <S) so far txjx-z X-ζ χ_ζ χ_ζ X Φ X Φ Φ X φ Φ Φ X Ρ φ Ll 41 0 Ο.Λ ε β β Φ Ρ Ρ Ρ m ν- / CN Γ χ-ζ 32 X 33 33 X X X 0 Ρ 0 ε Ρ 0 Ρ Ρ Ρ ο Φ Ρ • P 1 P f 1 1 1 1 I ι Γ Γ φ * 1 * CN 1 Ο ο υ Ο Ο U ο ο Ρ • Ρ Ρ I • Ρ Ρ Γ • Ρ · Ρ ρ 1 · Ρ CX CN Φ q q CN CN CN CN <Ν Ρ 4- 4— 4- Χ, ζ 1 1 I 1 1 1 1 1 φ CL Φ Γ-4 CL Φ CN CL Λ Φ CN CL

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• Ρ Ρ ρ 1-4 Ρ ΓΩ 1 Ρ • Ρ 1 Ρ • Ρ I rP • Ρ ιΡ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ φ ΓΩ ΓΩ ΓΩ 1 I 1 1 1 1 • Ρ 1 I | ΓΩ ιΡ ^ "1 ι-Ι ιΡ γΡ Ρ Ρ Ρ Ρ rL Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ ρ ρ γ-4 Ρ ΓΩ στ ΓΩ ΓΩ ΓΩ Ρ C Γ * f ¹ | • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ · Ρ • Η • Ρ • Ρ • Ρ • Ρ • Ρ • Η • Ρ • Ρ • Ρ Ή • Ρ 'Ρ • Ρ • Ρ | I 1 1 1 Ρ Ρ τ-1 1 φ φ φ q | 1 | I 1 1 1 1 1 1 1 1 | 1 | 1 | I 1 1 | 1 1 1 I q q q q C · Ρ • Ρ • Ρ 1-1 • Ρ φ C0 C0 <η C0 ο) co σ * ι cn cn co ΓΩ στ στ στ στ στ ΓΩ στ στ στ ΓΩ στ στ στ ΓΩ Φ Φ φ Φ Φ 1 1 1 'Ρ Ρ Ρ Ρ • ρ | 1 | 1 I 1 I 1 1 1 1 I I ι | I 1 I I 1 1 ι ι ι 1 • Ρ • Ρ • Ρ • Ρ ΓΩ ΓΩ ΓΩ Ρ 1 | | Ρ q q C q »q C α C q q C C C q fiction q C C C C α q C q q Ρ Ρ Ρ Ρ Ρ 1 1 1 φ • Ρ | φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ φ 1 1 1 1 f C q C! β X X • Ρ • Ρ ♦ Ρ • Ρ • ρ • Ρ • Ρ • Ρ • Ρ • Ρ · Ρ • Ρ Ρ • Ρ • Ρ • Ρ • Ρ • Ρ ♦ Ρ 'Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ Ρ Ρ γ-ι ι-4 Ρ φ φ Φ 1 ο Ο ρ χ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ • Ρ • Ρ • Ρ • Ρ • Ρ · Ρ • Ρ • Ρ 4 Ρ ρ φ ο 1 1 1 1 1 1 1 1 1 1 | | | 1 | 1 1 1 1 | 1 1 1 1 | Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ I φ φ ε ρ intact ι-1 rP 1-4 ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ ι-Ι Ρ ι-4 Ρ Ρ Ρ Ρ γ-1 ι-1 1-4 ι-4 φ φ φ φ Φ 1 1 1 γΡ ρ ε Γ φ • Ρ • Ρ 'Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ · Ρ • Ρ • Ρ Ρ • Ρ • Ρ • Ρ • rl • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ 1 1 | ε Β - Ρ ι-Ι 'Ρ Γ r | Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ Ρ 4 4 4 I Γ Ή • Ρ • Ρ CL 4 4 4 Φ & Ski Ski φ φ φ φ φ φ φ Ski φ φ φ φ φ φ φ φ φ φ φ φ φ 1 | 1 4 4 Ρ Ρ Ρ Ο 1 1 * Ρ | Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Β Ρ Ρ 4-r 1 1 Φ φ φ Ρ Ρ ι-4 X • Ρ • Ρ «Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ * Ρ • Ρ ♦ Ρ • Ρ • Ρ • Ρ • Ρ • Ρ 'Ρ ♦ Ρ • Ρ 'Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ • Ρ Ρ Ρ · Ρ 'Ρ • Ρ CL • Ρ Ο X Ό X X X X X X X X X X X X X X X X X X X X X X Ρ Ρ Ρ • Ρ 'Ρ χ X X Ο Ρ Ρ Ρ Ρ 1 1 | | 1 | 1 1 1 1 1 1 | | 1 | 1 1 | 1 1 | 1 | | φ φ Ski Ρ Ρ 1 | 1 Ν φ φ • 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 Η V Ρ φ Φ 4 4 4 • Ρ Η β β CN CN CN <Ν CN CN CN CN CN CN CN CN <Ν CN CN CN CN CN CN CN CN CN CN CN CN CN CN <Ν CN CN-CN.CN <Ν CN CN CN 1 CN 1 CN

i ΟΟ ^ Ο'-ΜΓΊ'ίυΊ ^ ΝΟΟζΓιΟ'-ΝΓΟ'ίΐΛ ^ Γ ^ ΰΟσ ^ Ο'- NfC'ÍV) ^ Or> COO'r-fNrC <ttn <D | ΠΜ ^ ί'ί'ί'ί'ί'ΝΤ'ί ^ 'ί'ίΐ / Ίΐ / Ίι / Ίΐ / Ίν'υΊίΛυΊΐΛΐϋ ^ Ό ^' ΧϊνΟ ^ '^' ΰΦυ-υ'Η '^' Γ ** r *.

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«0 CO (0 X X CD P-1 x r. UO X Φ φ Ph She 0 0 o X 42 ΟΊ I \ O 0 un She SHE un She Oh r * · en She X 1-4 rh X 0 1 1 CM * en cm Oh CM 44 o o She o o oh and ▼ - o i-O She r *. * - She -- CM · Ρ • rf ^υ Q o o She 0 and o oo r * o CM 0 cm and d en o o 0 She © *** » She X o She u oo • r- CM She ul 1Λ and in un S-ζ X Γ- Oh o un d o 0 l o en • · Xd 1 CM 3 nr * r * θ ′ 0 d 1 o un oo ο ι ο. ο. ο ι Oh 1 un »- T— r- r- * - and X 1 1 1 o 1 <t x I d O r * O O X w- o m I X X un X d X d * - v- r- en .. ·· .. <J- CM T II II II II II * 5 ^ 0 r * Oh * - • d C · Η C * She ex ex (X > H 4J * rl · N C N CX ex ex CL 3o8o 9q 3 ° Som m te- X X X X Ο MH 4-1 UH o o 05 Cd 05 0 0 0 <4-4 c c c c ti K cú o 0 O 4-4 P

Table σ \ σ »ο ο (continued)

1 »Ρ φ Β i was τ-1 ι-1 ι-1 ι-Ι Ζ— \ 1—1 • Ρ «Ρ Ρ Γ "-4 Η-ι ι-4 • P • P • Ρ · Ρ • Ρ rH · Ρ ti · Η Γ CM • Ρ • Ρ • Ρ P P Ρ Ρ Ρ • Ρ Ρ 0 Ρ ζ-k Ρ Ρ Ρ Φ Φ φ φ φ C Φ X Φ • Ρ γΡ φ the φ £ £ Β Β Β Ο 6 Ρ θ X • Ρ ε Β ρ r F r-l Γ Γ Γ X Γ «0 Γ 0 Ρ Γ Γ Ι-- 1 i-l i-l • l l rH rH Η-ι -R-4 οΧ Ρ Ρ 1-1 ι-4 • Ρ -Μ • P r-H • P rh P rh i was • Ρ · Ρ ι- » • Ρ ι — Ι «—1 rH co · ρ ι-Ι I · Ρ ιΡ φ 4-4 • Ρ r t ♦ Ρ Γ-4 Ρ • Ρ 1 · P • P Φ • H • Ρ 1 ι ♦ Ρ 1 · Ρ • Ρ · Ρ * I • Ρ • Ρ 'Ρ Ο 1 • Ρ I • Ρ • Ρ φ 1 ♦ Ρ 44 rh 44 44 Ρ Ρ τ- ρ 1 ρ ι * - Ρ X ρ • Ρ Ρ ^ Η ν— Ρ Ρ Ρ 10) 0) • P ω υ 1 Τ φ 1 Φ CM φ • Ρ 1 φ Ο Φ X Ό • Ρ | Φ φ φ • Η CM r- <£ t-4 B X ε £ 1-4 —Η Β «-Η Β X * Ρ Β Χ »-» Β 0 • Ρ X r — ι Ρ Ι-Η Ρ Β X (-1 0 F 0 r She Γ Ο 0 Γ ο Γ c Γ 0 ο F 0 Ο ι Ρ 42 ο ο Γ 0 Γ I 0 ο C Ν · Ρ N • P P • Ρ • rH Ν Ν • Ρ Ν · Ρ • Ρ · Ρ Ρ Ν ♦ Ρ Ρ Ν Λ φ <0 Ρ Ν «Ρ Ν • Ρ • Ρ Ρ Ν • Ρ <0x CD X • P X X cd «0 X Φ χ X X φ cd X χ cd C Β Ρ X co χ co X X φ CD X μ 0 P She £ ο ο Ρ Ρ ο Ρ ο Ο ο · Ρ Ο ο ρ g Γ Ρ Ο Ρ ο Ρ ο C Ρ Ρ 0 ♦ P P • P P F 44 Ρ • Ρ · Ρ Ρ • Ρ Ρ Ρ ρ 1 · Ρ Ρ Ν · Ρ £ CM φ Μ · Ρ Ρ • Ρ Ρ Ρ • Ρ Ρ X φ X φ CM <U 0) X X φ X Φ X φ * - X φ D-5 Ρ • ρ ο. φ X φ φ CM X X

ι cn ti ι en I

Ρ 1 1 1 Ρ · Ρ φ · Ρ I 1 1 P P P • P • P • P rh ι · ρ r-4 en en en 1 ρ · ρ ρ | en rH 1 1 and rh rh rh rh rh 1-4 r-l you • P | 1 · ρ 1 1 1 - <1 Ρ Φ c 1 · ρ 1-4 r- < r ^ She • P • P • P  P • P I I • P • P Φ you ι en 1 C C C · Ρ r-4 1 g Φ (2P • Ρ · Ρ • P 43 • P 0 r- r * r-1 γΡ ι ι en Φ Φ ρ · ρ rp · ρ • P Φ Φ P P P jh I I I I cn r-1 rh I I P X • rH • P • P C 1 · Ρ · Ρ · Ρ Φ Ρ · ρ Ό P • Ρ B φ Φ Φ Φ • P • P P «ρ Φ0ΡΡΡ0Φ44 | 1 P F Β £ £ 44 you you you α you you you you you B CD d d d ί · ρ φ ι ι ι F S φ un rh ι • d- F l F 1 Φ Φ Φ. φ Φ Φ Φ Φ Φ '0 44 Ρ | Ρ · Ρ ι — 4 ι — 4 γΡ «-ί 1 | *> • P rH | <r <t • P • P • P • P • P • P • P • P • P • P P l-1 Irish r ? 1 4J ρρρ 1 <'d-'d- P • P z — s 1 1 X P 44 P P P P P P P 43 • P She She 0 ι 1-1 | Ρ ρ ρ z-s | | | Φ P rH z— \ z— « z \ She X N N N  · Ρ «Ρ φ φ fP s ζ — s ζ— \ s Φ rH rH L-L P rh rh I-f jh P P P r ^ un She CO you CO I X X Β β Β · Ρ 1-4 rH r-4 F Β p • Ρ · Ρ • P Φ • P • P • P '0 '0 '0 '0 '0 • P P »P «Ρ • P ο ο Γ Γ F C · ρ · ρ · ρ <r F Φ 0 c c s P P P ^ H rP rP rh r-H P • rl Φ P P P : pp <r <r <t'Ptíc2e3 1 • d - 1 O 0 0 s 5i 44 44 44 give 44 Φ X B She She 0 X 0 1 1 1 4η 0 0 0 z 1 * r ^ 43 43 43 1 s B S .1 1 B 0 Γ N N N Ο 43 ζ ^- 'ζ— \ Ρ 43 r " Ο »x P u jh «D · • P • P • P un un un m un F P un • P • P • P ΜΙ ΟΟΟΟΡΡΡ X df o co co C0 1 Ό Ό I Φ ! ρ c Ρ Ρ Ρ Ν «<β« 0 She U 44 44 44 44 rP rh rh rh rh rh B rh rl rh ! 1 ι ρ ρ ρ 05, Χ, Χ 44 She Ο Φ 1 1 • P rH un un un • P • P • P • P • P B F • P ♦ P • P • P <- 1 1 1 1 1 1 1 2 Z * P • Ρ · Ρ • P X-P * * P P P P P Ό d P P P P  I I r-4 ι — 4 rH rH ι — t rH rH II Π Ό X X X 0 1 • d • d d Φ Φ P Φ Φ Φ £ rH rH _<r 4 _{> P} 4 »p» p '• ^ z 's 1 O 0 0 Jh en S S B B e X rl g S e S '· Ρ · Ρ4- »ΡΡΡΡΡΡ She U v- P P P X 1 rh rh l H • P P • P • P • P • P • P • P • P • P • P ! ρΡφφφφφφφ rh «Α <*> * rh Φ φ Φ 0 c • P • P • P Ό *SHE *SHE Ό P Ό rh Ό Ό Ό ajgaasssse • P X X * - • P e b s Ν Φ P P P • P She She v— '' -z • Ρ · Ρ Φ Φ Φ d d d d d un P d un un un Γ Γ ι ι ι> iii cn 1 1 1 I 1 1 1> « n M ·> F • Hen * CM CM CM cm es CM CM 1 CM CM CM CM CM CM CM CM CM CM CM I I I

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Preparation of intermediates

Example 8

3,5-Dimethyl-4-amino-thiophene-2-carboxylic acid methyl ester

A solution of 3,5-dimethyl-4-nitrothiophene-2-carboxylic acid methyl ester (45.2 g, 0.21 mol) in methanol (1000 mL) was treated with palladium (4.5 g, 10%, in the presence of carbon). After completion of the reduction, the reaction mixture is filtered, the catalyst is washed with methanol and the filtrate is evaporated to dryness. The crystalline residue was treated with diethyl ether to give the analytically pure title compound; mp 88-89 ° C.

Example 9

2,4-Dimethyl-3-aminothiophene

To a mixture of 890 ml (3 mol) of sodium bis (2-methoxyethoxy) aluminum hydride (70% toluene solution) and 600 ml of anhydrous toluene was added 100 g (0.58 mol) of 3-amino- A solution of 4-methylthiophene-2-carboxylic acid methyl ester in 700 ml of anhydrous toluene is added dropwise at a rate such that the mixture does not warm up to 55 ° C. After the addition, the mixture was stirred for an additional 30 minutes, and 1200 ml of 20% potassium hydroxide solution was carefully added in small portions at 0 ° C. The toluene layer was separated, dried over magnesium sulfate and concentrated in vacuo. The resulting brown liquid was distilled under reduced pressure to give the analytically pure title compound; fp. 49-52 ° C / l, 3 Pa.

Example 10

4-Methoxy-2-methyl-3-aminothiophene

N- (4-methoxy-2-methyl-thien-3-yl) -carbamic acid benzyl ester (55.4 g, 0.2 mol), potassium hydroxide (40 g, 0.7 mol), ethanol (600 ml) and Water (120 ml) was heated to reflux with vigorous stirring for 2 hours. The resulting solution was then concentrated in vacuo and the residue diluted with water (500 mL). The separated pale yellow oil is taken up in 400 ml of diethyl ether and the aqueous phase is extracted once with 400 ml of ether. The combined ethereal solutions were dried over sodium sulfate and filtered. Slowly anhydrous hydrogen chloride is passed through the filtrate for 30 minutes, ensuring that the temperature, sometimes cooled in an ice bath, does not exceed 10 ° C. 230 DEG C., m.p. the free base melts at 61-63 ° C.

Example 11

2-Methylthio-4-methyl-3-aminothiophene

Freshly prepared 6 g (0.22 g atom) of aluminum amalgam is added over 2 minutes

A solution of 18.9 g (0.1 mol) of 2-methylthio-4-methyl-3-nitrothiophene in 200 ml of water-containing diethyl ether. The vigorous reaction which begins after 5-10 minutes is controlled by ice-cooling. After 45 minutes, when the exothermic reaction was reduced and all the aluminum reacted, an additional 6 g of amalgamated aluminum was added.

The reaction mixture was carefully heated at reflux for 2 hours; during which the formation of thiophenamine is completed. The organic phase is decanted off and the residue is washed with two 50 ml portions of diethyl ether. The combined ethereal solutions were dried over magnesium sulfate and concentrated in vacuo. The crude title compound was obtained by distillation under reduced pressure; b.p. 79-81 ° C at 65 Pa.

Example 12

The compounds of formula (IX) listed below are described in the preceding Examples 8-11. can be prepared by any of the methods described in Examples.

12.1 1,3-dimethyl-5-ethoxy-4-aminopyrazole; Rf = 0.28 (9: 1 tetrahydrofuran / hexane);

12.2 3,5-Dimethyl-4-aminoisothiazole, m.p. 8284 C;

12.3 4-ethyl-2-methyl-3-aminothiophene, Rf = 0.25 (diethyl ether / hexane 2: 1);

12.4 4-n-Butoxy-2-methyl-3-aminothiophene, m.p. 25 ° C, Rf = 0.25 (diethyl ether / hexane 2: 1);

12.5 5-Ethoxy-3-methyl-4-aminopyrazole, m.p. 81-83 ° C;

12.6 3,5-Diethyl-1-methyl-4-aminopyrazole, m.p. 68-70 ° C / 0.13 Pa

12.7 3,5-Diethyl-4-aminoisoxazole, Rf = 0.39 (diethyl ether);

12.8 (3-Amino-4-methyl-thien-2-yl) -ethanol, m.p. 80-81 ° C;

12.9 (3-Amino-4-ethyl-thien-2-yl) -ethanone, m.p. 68 ° C;

12.10 (3-Amino-4,5-dimethyl-thien-2-yl) -ethanone, m.p. 120-123 ° C;

12.11 2-Ethyl-4-methyl-3-aminothiophene, m.p. 74-76 ° C / 1.3 Pa;

12.12 2,4-diethyl-3-aminothiophene, Rf = 0.24 (methylene chloride), n = 1 ²⁰ · 5511

12.13 2-Ethyl-4,5-dimethyl-3-aminothiophene, n ° = 1.5581;

Example 13

N- (2,4-dimethyl-thien-3-yl) acetoxy-acetamide

12.7 g (0.1 mol) of 2,4-dimethyl-3-aminothiophene,

To a mixture of 13.8 g (0.1 mol) of potassium carbonate, 20 ml of water and 150 ml of methylene chloride is added 15 g (0.11 mol) of acetoxyacetyl chloride at room temperature.

After the exotherm subsided, the mixture was stirred for an additional hour. The organic layer was then evaporated, washed with water, dried over magnesium sulfate and concentrated in vacuo. The solid residue was treated with hexane to give the analytically pure title compound; mp 110-112 ° C.

Example 14

N- (2,4-dimethyl-thien-3-yl) -hydroxy-acetamide

To a stirred solution of 15.9 g (0.07 mol) of N- (2,4-dimethylthien-3-yl) acetoxyacetamide in 300 ml of methanol is added a gentle stream of ammonia gas for 30 minutes.

-11193036

After the exothermic reaction (40 ° C) had subsided, quenched by cooling with cold water, the mixture was stirred for an additional 30 minutes, and the reaction solution was concentrated to dryness. The resulting solid was recrystallized from ethyl acetate to give the analytically pure title compound as colorless crystals; 81-87 ° C.

Example 15

N- (2-Ethoxyethyl) -4-methoxy-2-methylthiophen-3-amine in ml (0.245 mol) of sodium bis (2-methoxyethoxy) aluminum hydride (70% solution in toluene) and a solution of 9.4 g (0.041 mol) of N- (4-methoxy-2-methyl-thien-3-yl) -ethoxy-acetamide in 125 ml of anhydrous toluene are added dropwise with stirring to 30 ml of anhydrous toluene. After the exotherm had taken place, the mixture was stirred for a further 90 minutes, and the resulting solution was carefully added in small portions at -10 ° C to 100 ml of 20% potassium hydroxide solution. The toluene layer was separated and the aqueous layer was extracted twice with 100 mL of toluene. The combined toluene solution was dried over sodium sulfate and concentrated in vacuo. The resulting light brown liquid was analytically pure; Rf value: 0.32 (hexane: diethyl ether 1: 2).

Example 16

N - [(Methoxymethyl) ethyl] -2,4-dimethylthiophen-3-amine

A solution of 6.4 g (0.05 mol) of 2,4-dimethyl-3-aminothiophene and 5.3 g (0.06 mol) of methoxyacetone in 100 ml of anhydrous toluene is refluxed until the theoretical amount is reached. water is precipitated in the water trap (2.5 hours). The toluene solution was then allowed to cool to room temperature and concentrated in vacuo. The residual crude Schiff base was of sufficient purity for the next step.

9.2 g (0.048 mol) of the above material are dissolved in 100 ml of anhydrous toluene and added without cooling to 28 ml (0.098 mol) of sodium bis (2-methoxyethoxy) aluminum hydride (70% toluene solution) in 15 ml prepared with anhydrous toluene and thoroughly mixed.

After the exothermic reaction (44 ° C) was complete, the mixture was stirred for a further 90 minutes and the brown reaction solution was carefully added in small portions at -10 ° C to 40 ml of 20% potassium hydroxide solution. The toluene layer was then separated, dried over sodium sulfate and concentrated in vacuo. The resulting oil was distilled under reduced pressure after column chromatography on silica gel (eluting with 3: 1 hexane: diethyl ether); boiling point 94-95 ° C at 1.3 Pa.

Example 17

N- (5-Ethyl-l, 3,4-oxadiazol-2-yl-methyl) -2,4-dimethyl-thiophene-3-amine

12.7 g (0.1 mol) of 2,4-dimethyl-3-aminothiophene, 14.6 g (0.1 mol) of 2-chloromethyl-5-ethyl-1,3,412

A mixture of oxadiazole and 13.8 g (0.1 mol) of potassium carbonate in 150 ml of anhydrous dimethylformamide was stirred at 80 ° C for 20 hours.

The reaction mixture was cooled to room temperature, poured into water (400 mL) and the aqueous dimethylformamide solution was extracted with diethyl ether (150 mL x 3). The combined ethereal extracts were dried over anhydrous sodium sulfate and concentrated in vacuo. The resulting brown oil was eluted on a silica gel column with hexane: diethyl ether (1: 1) to afford the title compound as an analytically pure orange liquid; R f = 0.2 (1: 1 ether / hexane).

Example 18

N- (2,4-Dimethyl-thien-3-yl) -glycine hydrazide g (0.412 mol) N- (2,4-dimethyl-thien-3-yl) -glycine methyl ester and 42 g ( Hydrazine hydrate (1.3 mol) in alcohol (350 ml) was stirred at room temperature for 24 hours. The mixture was then concentrated in vacuo. After addition of 150 ml of water, the residue was extracted 4 times with 500 ml of ether. The ether layer was dried over sodium sulfate and evaporated to dryness to afford the analytically pure title compound; mp 68-70 ° C.

Example 19

N- (2,4-Dimethyl-thien-3-yl) -N- (4-methyl-5-mercapto-t, 2,4-triazol-3-ylmethyl) -amine g (0.075 mol) N- (2,4-Dimethylthien-3-yl) glycine hydrazide and 5.5 g (0.075 mol) of methyl isothiocyanate in 100 ml of ethanol are refluxed for 4 hours. The reaction mixture was cooled to 6 ° C and the precipitate was collected by filtration to give the title pure compound; mp 184-187 ° C.

Example 20

N- (2,4-dimethyl-thien-3-yl) -N- (4-methyl-5-methylthio-l, 2,4-triazol-3-yl-methyl) -amine

9.5 g (0.037 mol) of N- (2,4-dimethylthien-3-yl) -N- (4-methyl-5-mercapto-1,2,4-triazol-3-ylmethyl) - amine, 1.1 g triethylbenzylammonium chloride solution in 100 ml toluene and 30 ml 50% aqueous sodium hydroxide solution

Dimethyl sulfate (4.7 g, 0.037 mol) was added. After stirring for 5 hours at room temperature, the organic layer was separated, washed with water (3 x 100 mL), dried over magnesium sulfate and evaporated to dryness. The residue was recrystallized twice from ether to give the title compound, m.p. mp 92-96 ° C.

Example 21

N- (2,4-Dimethyl-tert-3-yl) -N- (5-methyl-1,3,4-thiadiazol-2-ylmethyl) -amine g (0.05 mol) N- ( 2,4-Dimethyl-thien-3-yl) -glycine hydrazide in 175 ml of methylene chloride

5.5 g (0.05 mol) of acetic anhydride are added dropwise. The mixture was stirred at 20 ° C for one hour and then concentrated to dryness. The oily residue is dissolved in 150 ml of pyridine and 11.1 g (0.05 mol) of phosphorus pentasulfide are added.

-12193036 in small details. During the addition, the mixture was heated to 48 ° C. The mixture was refluxed for 2 hours and then stirred at room temperature for an additional 16 hours. After evaporation to dryness, the residue is dissolved in methylene chloride and the solution is treated successively with ice water, cold dilute sodium hydroxide solution and water, dried over sodium sulfate and evaporated to dryness. Chromatography on a silica gel column gives the title pure compound as an oil; Rf = 0.23 (6: 4 ethyl acetate: hexane).

Example 22

N- (2,4-dimethyl-thien-3-yl) -N- (5-methyl-l, 2,4-triazol-3-yl-methyl) -amine

To a stirred solution of sodium hydroxide (2.2 g, 0.055 mol) in methanol (125 ml) was added acetamidine hydrochloride (5 g, 0.05 mol). After 15 minutes, N- (2,4-dimethylthien-3-yl) glycine hydrazide (10 g, 0.05 mol) was added and the mixture was refluxed for 18 minutes. After evaporation to dryness, the residue is treated with methylene chloride and the insoluble by-products are filtered off. The methylene chloride was evaporated to give the title compound; 85-87 ° C.

Example 23

N- (2,4-Dimethyl-thien-3-yl) -glycine-isopropylidene-hydrazide g (0.035 mol) of N- (2,4-dimethyl-thien-3-yl) -glycine-hydrazide in 50 ml of acetone for 2 hours. stir for a while at room temperature. The crystallized title pure compound is filtered off; 126-128 ° C.

Example 24

The following II. The compounds of formula (VII) in Table 13 are shown in Table 13-23. is prepared according to any of the Examples.

II. spreadsheet

Example Arii Y Identification data 24.1 2 H -dimethyl-thien-3-yl 2-methoxyethyl R f = 0.32 (3: 1 diethyl ether / hexane) 24.2 2,4-dimetí1-thien-3-yl ethyl R f = 0.23 (diethyl ether / hexane 1: 1) 24.3 2,4-dimethyl-thien-3-yl 2-thienylmethyl R f = 0.38 (diethyl ether / hexane 1: 1) 24.4 2,4-dimethyl-thien-3-yl 2-furylmethyl R f = 0.39 (diethyl ether / hexane 2: 1) 24.5 2-methylthio-4-methyl-thien-3-yl 2-methoxyethyl fp. 86 ° C / 0.13 Pa 24.6 1,3,5-trimethyl-pyrazol-4-yl 2-methoxyethyl fp. 92-94 ° C, 0.13 Pa 24.7 1-methyl-3,5-diethyl-pyrazol-4-yl 2-methoxyethyl R f = 0.38 (4: 6 acetone / hexane) 24.8 1,3,5-trimethyl-pyrazol-4-yl ethyl R f = 0.2 (ethyl acetate / methanol 2: 1) 24.9 3-methyl-5-ethoxy-pyrazol-4-yl 2-methoxyethyl Rf = 0.25 (9: 1 ethyl acetate / methanol) 24.10 2,4-dimethyl-thien-3-yl 2-ethoxyethyl R f = 0.48 (diethyl ether) 24/11/11 2,4-dimethyl-thien-3-i1 2-n-propoxy-ethyl R f = 0.57 (diethyl ether) 24.12 2,4-Dimethylamino-thien-3-yl 2,2,2-trifluoroethyl n "= 1.4786 24.13 2,4-diethyl-thien-3-yl 2-methoxyethyl π »= 1.5238 24.14 2-methyl-4-ethyl-thien-3-yl 1-methyl-2-methoxyethyl fr. 98-100'C 11.7 Pa 24.15 Etí1-4-2-methyl-thien-3-yl l-methyl-2-ethyl-metcxi Rf = 0.52 (7: 3 ether / hexane) 24.16 2,4-dimethyl-thien-3-yl 2-methyl-proper-2-yl R f = 0.55 (diethyl ether / hexane 1: 1) 24.17 2,4-dimethyl-thien-3-yl pyrazin-2-yl-ir.etil 24.18 2,4-dimethyl-thien-3-yl 2-methyl-thiazol-5-ylmethyl 24.19 2,4-dimethyl-thien-3-yl 1,2,4-oxadiazcl-5-ylmethyl Rf = 0.15 (methylane chloride) 24.20 2,4-dimethyl-3-yl tien. -CHjCONCHjh n "= 1.5579 24.21 2,4-dimethyl-thien-3-yl me toxicocarbonyl-methyl fp. 82-87 ° C / 0.65 Pa

Example 25

N- (2-methoxy-carbonyl-3,5-dimethyl-thien-4-yl) choroacetamide

12.25 g (0.066 mol) of 3,5-dimethyl-4-aminothiophene-2-carboxylic acid methyl ester, 9.1 g of 50 (0.066 mol) of potassium carbonate, 25 ml of water and 150 ml of methylene chloride without cooling, 7.5 g (0.066 mol) of chloroacetyl chloride were added. After the exotherm (36 ° C) was complete, the mixture was stirred for an additional hour. The organic layer was then separated, washed with water and dried over anhydrous sodium sulfate.

After removal of the solvent, the desired product is obtained in the form of colorless crystals; op. 157-158 ° C.

Example 26

N- (2-Chloro-3,5-dimethyl-thien-4-yl) choroacetamide

To a solution of 5.0 g (0.0245 mol) of N- (2,4-dimethylthien-3-yl) chloroacetamide in 50 ml of anhydrous methylene chloride was stirred at 0 ° C for 3.3 g ( Sulfuryl chloride (0.0245 mol) was added dropwise.

After the addition, the reaction mixture was allowed to warm to room temperature and stirred for an additional 20 hours. The solvent was removed in vacuo and the crystalline residue was triturated with hexane to give the pure title compound; mp 166 ° C with decomposition.

Example 27

N- [2- (1,1-Diethoxy) ethyl-4-methylthien-3-yl] chloroacetamide (0.065 mol) N- (2-acetyl-4-methylthien-3-yl) chloroacetamide was dissolved in a warm mixture of 60 g of anhydrous ethanol, 60 g of triethyl ortho formic acid and 7 drops of concentrated hydrochloric acid at 50 ° C. After 30 hours at room temperature, the mixture was concentrated in vacuo (50 ° C / 3 Pa) and the resulting brown syrupy material was silica

-13193036 on a gel column. Elution with hexane / diethyl ether (2: 1) gave the title compound as colorless crystals. 57-58 ° C.

Example 28

N- [2- (1-Methoxyimino) ethyl-4-methylthien-3-yl] chloroacetamide

1.5 g (0.0065 mole) of N- (2-acetyl-4-methylthien-3-yl) chloroacetamide and 6.6 g (0.14 mole) of methoxyamine were prepared in 50 ml of anhydrous toluene. of a solution of 5 g of molecular sieve (3 A) is refluxed for 7 hours.

The yellow reaction mixture was then filtered and concentrated in vacuo. The resulting crude color / anti isomer mixture was separated by chromatography using hexane / diethyl ether as mobile phase.

First 0.6 g of pure isomer (color isomer) was eluted; mp 101-102 ° C; (R f = 0.33, hexane / ether 1: 1). Further elution of the silica gel column afforded an analytically pure anti-isomer (0.4 g); m.p. 87-89 ° C;

Rf value; 0.21.

Example 29

25-28. By the method of Examples ₁₅ was prepared the following compound (III) of formula:

Example Aryl moiety Identification data 29.1 2-methoxycarbonyl-4-methyl-thien-3-yl op. 118-119 29.2 2-methylthio-4-methyl-thien-3-yl op. 105-106 ° C 29.3 2,4-dimethyl-thien-3-yl op. 128-129 ° C 29.4 3,5-dimethyl-isoxazol-4-yl op. 96-98 ° C 29.5 3,5-diethyl-isoxazol-4-yl op. 67-69 ° C 29.6 4-methyl-thien-3-yl op. 93-96 ° C 29.7 2-methyl-4-ethyl-thien-3-yl op. 114 ° C 29.8 2 tetraethylammonium 4-methoxycarbonyl-thien-3-yl op. 144-145 ° C 29.9 2,4-dimethyl-furan-3-yl op. 95-97 ° C 29.10. 3,5-dimethyl-isothiazol-4-yl op. 104-106 ° C 29.11 3-methyl-5-ethoxy-pyrazol-4-yl op. 125-127 ° C 29.12 2-ethoxy-karboni1-N, 3,5-trimethyl-PIR rol-4-yl op. 163-165 ° C 29.13 2-ethyl-4-methyl-thien-3-yl op. 105 ° C 29.14 2,4-diethyl-thien-3-yl op. 145 ° C 29.15 2-methyl-carbonyl-4-methyl-thien-3-yl op. 110 ° C 29.16 2-methyl-4-n-butoxycarbonyl-thien-3-yl op. 129-130 ° C 29.17 2-ethyl-4,5-dimethyl-thien-3-yl op. 147-148 ° C.

Example 30 45

N- (2,4-dimethyl-thien-3-yl) -N- (methoxy-ethyl) -hydroxy-acetamide

A solution of 18.4 g (0.1 mol) of N- (2,4-dimethylthien-3-yl) hydroxyacetamide in 50 ml of anhydrous dimethyl 50-formamide was added dropwise with stirring to a solution of 3.0 g (0, 1 mol) of sodium hydride (80% dispersion in mineral oil) in 50 ml of anhydrous dimethylformamide. After the exo-55 thermal reaction (50 ° C) was quenched, the sodium salt solution was allowed to warm to room temperature and then 10.4 g (0.1 L) was added.

A solution of 2-chloroethyl methyl ether in 20 ml of anhydrous dimethylformamide. After the addition, the resulting mixture was stirred for 4 hours

Heat at 100 ° C and evaporate to dryness (40 ° C / 13 Pa):

The residue is taken up in 200 ml of diethyl ether, washed with 250 ml of water, dried over magnesium sulphate and filtered. After evaporation of the filtrate, the residual oil was chromatographed on a silica gel column. Elution with ether gives the desired product as an analytically pure viscous liquid. Rf = 0.25 (ether).

Example 31

By following the procedure described in Example 30, the following compounds of formula (II) are prepared; Ar is 2,4-dimethylthien-3-yl.

-14193036

Example Y Identification data 31.1 -CH _z CH = NOCH ₃ R f = 0.21 (3: 2 hexane / ethyl acetate) 31.2 -ch ₂ ch = noc h, Rf = 0.25 (3: 2 hexane: ethyl acetate) 31.3 -CH ₂ C = N ₀ CH ₅ CH 3 op. 69-71 ° C 31.4 -ch _{! 1} -c = noc ₁ h Rf = 0.27 (3: 2 hexane: ethyl acetate) 31.5 CH? - (jlHCH = NOCHj CH? R f = 0.31 (3: 2 hexane / ethyl acetate) 31.6 -CHCH = NOCjH _r CH * Rf 0.3 (3: 2 hexane / ethyl acetate) 31.7 1,3-dioxolan-2-ylmethyl Rf = 0.12 (3: 2 hexane: ethyl acetate)

Example 32

N- (4-Methoxy-2-methyl-thien-3-yl) ethoxy-acetamide

To a mixture of 9.8 g (0.068 mol) of 4-methoxy-2-methyl-3-aminothiophene, 9.45 g (0.068 mol) of potassium carbonate, 35 ml of lime and 100 ml of methylene chloride is added 8.4 g without cooling. g. (0.069 mol) of ethoxyacetyl chloride in 20 ml of methylene chloride.

After the exotherm (32 ° C) subsided, the mixture was stirred for an additional hour. The organic layer was separated, washed twice with 150 mL water and dried over anhydrous sodium sulfate.

The solvent was removed by rotary evaporation and the resulting residue was subjected to silica gel column chromatography. Elution with hexane / diethyl ether (1: 1 v / v) afforded the title compound in analytical purity; op. 40-41 ° C.

Example 33

In a manner analogous to that described in Example 32, the amides of formula ArNHCOY _{3 are} prepared as follows:

Example Aryl moiety ^Y i Identification data 33.1 2,4-dimethyl-thien-3-yl methoxymethyl mp 62-63 ° C 33.2 2 N-dimethyl-thien-3-yl methyl op. 168-169'C 33.3 2,4-dimethyl-thien-3-i1 2-furyl op. 140-142 ° C 33.4 2,4-dimethyl-thien-3-yl 2 tiení1 op. 164-165 ° C 33.5 1,3,5-trimethyl-pyrazol-4-yl methoxymethyl op. 85-87 ° C 33.6 1-methyl-3,5-diethyl-pyramids methoxymethyl fp. 120 / 0.13 Pa 33.7. zol-4-yl 3-methyl-5-ethoxy-pyramids methoxymethyl op. 128-130 33.8 zol-4-yl 2,4-dimethyl-thien-3-yl ethoxymethyl op. 37-38 ° C 33.9 2,4-dimethyl-thien-3-yl n-propyloxy op. 43-45'C 33.10 2,4-dimethyl-thien-3-yl methyl trifluoro op. 94-97'C 33.11 2,4-diethyl-thien-3-yl -methyl methoxymethyl op. 48r49C

Example 34

Benzyl-N- (4-Methoxy-2-methyl-thien-3-yl) carbamate

63.6 g (0.23 mole) of diphenylphosphoryl azide and 24.4 g (0.23 mole) of triethylamine are added simultaneously with stirring to 36.5 g (0.21 mole) of 4-methoxy-2-methylmyophene To a suspension of -3-carboxylic acid in 300 ml of anhydrous benzene.

The resulting reaction mixture was heated at reflux for 1 hour and then benzyl alcohol (25 g, 0.23 mol) was added.

After 3.5 hours at 78 ° C, the reaction mixture was cooled to room temperature, diluted with 350 mL of diethyl ether and quenched with 250 mL of 5% hydrochloric acid, 250 mL of saturated sodium bicarbonate solution and 200 mL of saturated sodium chloride. chloride solution. After drying over sodium sulfate, the solvent was removed by rotary evaporation and the resulting crystalline residue was triturated with pentane. The analytically pure title compound melts at 107-108 ° C.

Example 35

By following the procedure described in Example 34 and using the appropriate carboxylic acid, the following carbonates are prepared.

35.1 Benzyl N- (2,4-dimethylfuran-3-yl) carbamate, m.p. 103-105 ° C;

35.2 Benzyl N- (4-n-butoxy-2-methyl-thien-3-yl) -carbamate, m.p. 83C.

Example 36

4-Methoxy-2-methyl-thiophene-3-carboxylic acid

The title compound is obtained by purification of the corresponding ethyl ester (potassium hydroxide); mp 127 ° C.

-15193036

Example 37

In a manner analogous to that described in Example 36, 4-n-butoxy-2-methylthiophene-3-carboxylic acid is prepared; op. 66-68 ° C.

Example 38

4-Methoxy-2-methylthiophene-3-carboxylic acid ethyl ester (50 ml) was added dropwise at room temperature.

18.6 g (0.1 mol) of ethyl 4-hydroxide-2-methylthioylene-2-carboxylic acid, 10 ml (0.105 mol) of dimethyl sulfate and 2.3 g (0.01 mol) of benzyl of triethylammonium chloride in 100 ml of methylene chloride. After refluxing for about 15 minutes, the reaction mixture was worked up to give the title compound; Rf 0.36 (diethyl ether / hexane 2: 1).

Example 39

Methyl 3,5-dimethyl-4-nitrothiophene-2-carboxylic acid

To a cooled solution of 51.4 g (0.3 mol) of 3,5-dimethylthiophene-2-carboxylic acid methyl ester in 200 ml of glacial acetic acid (0 ° C) under vigorous stirring for 30 minutes was added 30 ml of fuming nitric acid (specific gravity = 1). (5 g / cm ³ ) and 120 ml of acetic anhydride are added dropwise. After the addition, the resulting brown solution was stirred for an additional hour at 5 ° C and then poured into 3000 ml of ice water.

The aqueous phase was extracted twice with 500 ml of diethyl ether. The ethereal extracts were washed with water and with a 1% sodium bicarbonate solution, dried over sodium sulfate and concentrated in vacuo.

The residue was subjected to silica gel column chromatography. Elution with 10: 1 v / v hexane / diethyl ether gave the title compound; m.p. 87-88 ° C.

Example 40

In a manner analogous to that described in Example 39, but starting from 1,3-dimethyl-5-ethoxy-pyrazole, 1,3-dimethyl-5-ethoxy-4-nitro-pyrazole was prepared. Rf value: 0.37 (on silica gel with diethyl ether).

Impact studies

Example 41

In the case of pre-emergence herbicide treatment, a mixture of peat medium and sand was filled into driving pots of cm diameter. The mixture of peat medium and sand was sprayed with the spray liquid containing the active compound to be tested (e.g., Example B), and seeds of Lepidium sativum, Agrostis alba, Avena sativa and Lolium perenne were sown in each pot, and Avena sativa and Lolium perol were sown after sowing. seeds were covered in a thin layer (0.5 cm) with a mixture of peat medium and sand. The pots were kept for 21 days at room temperature with 1416 hours of light per day (sunlight or equivalent).

The herbicidal activity of the test substance was determined after 21 days. The definition of different plant damage! scale and character.

In the previous study, the active compounds of the formula I were applied in an amount of 1.4 and 5.6 kg / ha, respectively.

We found a herbicidal effect, that is, significant damage to the tested plants.

Example 42

Herbicide after emergence treatment

The procedure described in Example 41 was followed except that the test substances were treated when the plants were 2-4 leafy and the seeds of the plants were sown so that the plants were 2-4 leafy. reach at the same time.

The active compounds of the formula (I) were again applied in amounts of 1.4 and 5.6 kg / ha. Herbicidal activity was determined 21 days after treatment and evaluated in a manner analogous to that described in Example 41. We have a herbicidal effect.

Example 43

The effect of representative agents of the present invention was evaluated in the following pre-emergence study.

30. 40 cm drive boxes were filled to a depth of 6 cm with a mixture of peat medium and sand. The upper surface of the mixture of peat medium and sand was sprayed with an aqueous spray solution containing the active ingredient at a given concentration (e.g., the agent prepared in Example B). The spray juice corresponded to 600 liters of water per hectare. This assay was repeated with different concentrations of spray leaves and the concentration selected to give the desired application rate. Six crowns were planted in each crate. The number of seeds of each plant species sown is the germination of seeds! and the initial growth height of the particular plant. After seeding, the treated surface was covered in a thin layer (about 0.5 cm) with a mixture of peat medium and sand.

The prepared flasks were stored for 28 days at 20-24 ° C and 14-17 hours / day.

The herbicidal activity of the active substance was determined after 28 days. The determination was made by looking at the degree and quality of damage to different plants. Particularly advantageous herbicidal activity was observed, inter alia, in Table 25, 26, 47, 48,

55, 75, 84 and 86. Treatment with a dose of 1 kg / ha of the active ingredient gave some results in Annex III. Table I.1.

-1 631

Example 44

Post-emergence treatment

Further evaluation of some representative compounds of Formula I was performed on post-emergence treatment in the same manner as the pre-emergence treatment described in Example 43, except that the spray containing the active ingredient was applied at 2-4 leaf age. To this end, different plant species were sown with time. The conditions of the greenhouse 193036 (temperature, light) were the same as in Example 43. The determination of the herbicidal effect was also performed as described in Example 41 Mó ₅ Don 28 days after treatment.

Particularly advantageous herbicidal activity has been found, inter alia, in the compounds of formula I. with the active compounds 25, 26, 47, 48, 55, 75, 84 and 86 as shown in Table II. Some results were obtained with the application rate of 5 kg / ha of active compound in Table IV. are summarized in Table.

III. spreadsheet

Before hatching treatment 1 kg / ha Examiner tested, damage, % Treated active ingredient 25 26 | 47 48 55 75 84 86 Amaran.retrof1. SALT 90! 100 100 100 100 80 90 Capsella b.p. 80 1G0 100 oO 90 70 70 90 Chenop. alb. 80 80 90 50 20 50 60 60 Galium aparine 80 10 50 0 10 10 50 10 Senecio vulg. SALT 80 80 80 80 100 90 100 Stellaria media 90 70 70 80 50 50 / U d Alfalfa 80 60 60 50 CO 10 70 ⁹⁰ i Puppet 0 0 20 20 0 0 , ₃ 10 i Carrot 80 90 .90 90 70 100 80 90 Cotton 20 0 10 ^{C 0} 0 20 0 Flax 80 30 60 50 30 0 20 10 Potato 0 10 10 0 0 0 ⁰ 0 ί Soy 5o 10 30 30 0 10 30 30 Sugar beet 60 10 10 0 0 ⁰ 20 30 Rape 10 0 20 0 0 0 20 10 Sunflower 0 10 30 50 0 0 - “1 10 Agropyron. repens 90 100 90 60 80 90 90 70 Agrostis alba ICO 100 100 100 100 100 100 ICO Alopec. myös. 90 90 80 80 50 80 30 eighth to one tenth 1 Apera sp.venti. 100 100 100 100 100 100 100 100 Avena fatua 80 SALT 80 1--1 ι ι ¹ í O f 80 90 50 90 Echinochloa c.g. 90 100 90 90 90 100 90 90 Maize 20 30 50 30 0 50 60 Wheat 70 100 90 90 · 0 100 6U 70

-17193036

Table III (cont'd)

Damage, *

Handled plant authorities material 9 22 27 43 kg / ha 1 5 1 5 1 5 1 5 Amaran.retrof1. 90 100 90 100 70 80 100 100 Capsella b.p. 60 70 60 90 30 80 90 100 Chenop. alb. 50 60 50 90 50 60 90 100 Galium aparine 30 80 60 80 0 10 50 80 Senecio vulg. 70 80 100 100 70 90 50 100 Stellaria media 50 70 30 60 40 60 70 100 Alfalfa 50 80 70 90 60 60 80 100 Puppet 0 0 60 90 0 10 0 80 Carrot 60 90 100 100 60 70 60 100 Cotton 0 20 0 0 0 0 0 30 Flax 30 30 80 90 40 20 0 70 Potato 0 0 50 70 0 0 0 0 Soy 10 10 40 70 30 40 40 80 Sugar beet 10 30 50 80 20 30 20 90 Rape 0 20 .10 20 30 30 0 10 Sunflower 0 0 30 50 0 0 0 20 Agropyron repens 90 90 90 90 50 80 100 90 Agrostis alba 100 100 100 100 100 100 100 100 Alopec. myös. 70 100 30 100 70 70 70 100 Apera sp.venti. 100 100 100 100 100 100 100 100 Avena fatua 30 60 60 90 10 50 60 80 Echincchloa c.g. 100 100 100 100 90 100 90 100 Maize 30 90 40 90 60 90 30 100 Wheat 100 90 50 90 50 90 50 100

-18193036

III. Table (cont.)

Damage, \ Handled plant Active substance j 52 77 78th 85 Kg / ha 1 5 1 5 1 5 1 5 Amaran.retrofl. 100 100 1OO IOO IOO 100 100 IOO Capsella b.p. 60 70 60 70 50 90 60 70 Chenop. alb. 20 50 30 60 10 60 60 60 Galium aparine 10 60 20 50 0 20 50 80 Senecio vulg. 90 100 90 100 50 100 90 90 Stellaria media 40 90 100 100 60 100 60 80 Alfalfa 10 50 40 60 50 60 70 70 Puppet 0 30 30 50 10 20 10 40 Carrot 90 100 20 100 0 30 70 LOO Cotton 0 30 0 0 0 0 10 30 Flax 10 30 60 100 40 70 50 50 _Potato 0 10 30 50 0 10 0 0 Soy 10 60 10 50 0 10 10 20 Sugar beet 20 30 0 10 0 20 10 30 Rape 0 10 10 50 0 20 20 30 Sunflower 0 50 0 20 10 0 0 10 Agropyron repens 60 100 70 70 50 70 90 100 Agrostis alba 100 100 100 100 90 100 100 100 Alopec. myös. 60 80 50 70 10 50 90 90 Apera sp .. venti. 100 100 100 100 100 100 100 100 Avena fatua 80 100 70 90 20 60 60 90 Echinochloa c.g. 100 100 80 100 70 80 100 100 Maize 40 100 30 90 0 10 60 90 Wheat 100 100 60 70 30 30 80 100

-19193036

III. Table (cont.)

Damage, % Handled plant Active substance 87 98 alachlor Kg / ha 1 5 1 5 1 5 Amaran.retrof1. 80 100 100 100 90 100 Capsella b.p. 80 80 100 100 40 80 Chenop. alb. 70 80 80 100 30 50 Galium aparine 70 80 0 30 0 0 Senecio vulg. 80 100 100 100 0 40 Stellaria media 80 100 100 100 40 60 Alfalfa 60 70 30 60 30 60 Puppet 20 50 20 30 10 20 Carrot 70 90 60 100 10 50 Cotton 10 30 0 10 0 0 Flax 40 60 90 100 30 50 Potato 0 0 0 50 0 0 Soy 0 10 10 10 0 0 Sugar beet 10 50 60 100 0 30 Rape 40 40 40 90 0 20 Sunflower 0 10 0 0 0 0 Agropyron repens 100 100 80 100 40 70 A.grostis alba 100 100 100 100 100 100 Alopec. myös. 90 100 60 80 20 50 Apera sp.venti. 100 100 100 100 100 100 Avena fatua 70 80 30 70 40 80 Echinochloa c.g. 90 100 80 100 70 80 Maize 90 60 70 80 0 0 Wheat 90 80 70 90 50 90

-20193036

ARC. spreadsheet

---- Post-emergence treatment 5 kg / if Vi 7th Scarf b ^ -t-ÓAnvArr. .damage, She. ^Treated Ii h plant 25 26 47 48 * 55 75 84 86 * Amaran.retrof1. 90 80 70 50 80 60 80 fin 2ϋ Capsella b.p. 80 60 20 20 80 50 80 60 Chenop. alb. 90 40 40 20 20 40 30 60 Gáliam aparine 80 60 40 30 80 20 70 60 Senecio vulg. 80 50 70 80 90 90 80 90 Stellaria media 90 50 60 ¹⁰ 30 40 60 40 Alfalfa 80 60 '20 10 i 20 / U 7-! / u 1 Puppet 100 20 30 20 20 30 30 50 i Carrot 70 90 30 100 80 100 in 100 · I Cotton 70 60 50 40 50 60 70 70! 'í Flax 80 70 90 100 80 90 40 i needle Potato 70 _Ί 30 20 10 10 10 40 Ίο Soy 90 30 ³⁰ 30 20 20 3 <Ί -aq Sugar beet 30 20 70 0 10 10 0 ¹⁰ i Rape 40 20 10 10 30 60 50 40 Sunflower 60 50 30 80 40 60 ₉ 0 50 Agropyron repens 70 30 70 50 50 50 30 50 Agrostis aiba - - - - - - 80 - Alcpec. myös. 80 90 80 70 60 90 90 Apera sp.venti. 90 100 100 100 100 100 90 90 Avena fatua 90 100 90 80 90 100 100 100 Echinochloa c.g. 1.) 2.) Oo 90 60 80 80 80 80 90 90 100 70 80 80 CD · - · 90 100 Maize 80 60 100 90 30 30 70 80 Wheat 70 90 80 50 ' 10 60 _ 60 80 Rice 2) 40 30 10 50 j 30 30 ^ ^{1- 1} 4 30 1 40

* 4 kg / ha 1) land 2) flooded

-21193036

Field tests

Further examinations of the active ingredient with serial number 25 were carried out before hatching by the so-called Multicrop-Fieldscreening method under the following conditions:

Crops:

soya (Steele variety) (Word), cotton (Stoneville variety 213) (Gya), corn (LG 11 variety) (Ku), wheat (Svenno variety) (Bu);

weeds:

Alopecurus pratensis (AL),

Echinochloa crus galli (Ech),

Galium aparine

Chenopodium album and polyspermum are dicotyledons

Amaranthus retroflexus (All weeds except Alopecurus pratensis we sowed were of natural origin.)

Spray rate: 750 liters / ha, number of replicates: 3 evaluation: 28 days after treatment, known comparators: alachlor (a-chloro-2 ', 6'-diethyl-N-methoxymethylacetanilide) and metallochloro [a-chloro -2'-ethyl-6'-methyl-N- (1-methyl-2-methoxyethyl) acetanilide].

The herbicidal effect observed is shown in the following table.

agent kg / ha Weave Gya ku Bu Al / Ech dicotyledons 25th 0.6 0 0 10 63 92 43 1, 25 3 3 53 80 100 67 2.5 5 7 80 92 100 87 alachlor 1.25 0 0 0 10 43 43 2.5 0 3 0 53 78 57 metálaklór 1.25 0 0 0 33 100 30 2.5 0 0 0 73 100 43

The above results demonstrate an herbicidal activity that is equal to or better than that of commercially available agents against monocotyledonous weeds and better than that of known agents against dicotyledonous weeds. The herbicidal effect is selective in soya and cotton as well as at the lowest application dose in maize.

Claims (7)

PATENT CLAIMS CLAIMS 1. An herbicide comprising from 0.1% to 95% by weight of a chloroacetamide derivative of the formula (I) Z is CH; X and X ₂ are each C 1 -C 4 alkyl or One of X ₁ and X ₂ is C 1 -C 4 alkyl and the other is C 1 -C 4 alkoxy or -C (= NOCH ₃ ) CH _3; and Y is di (C 1 -C 4 alkyl) aminocarbonyl, C 1 -C 4 alkoxy, 1-pyrazolyl, 3,5-dimethyl-1-pyrazolyl or 2- (C 1 -C 4 alkyl) -1,3 Substituted with 4-triazol-4-yl Or C 1-4 alkyl C2-C5 alkynyl group, solid or liquid carrier or diluent, preferably natural or artificial mineral powder, aliphatic, aromatic or cyclic hydrocarbon, water, mineral oil fraction, and surfactant additive, preferably 1022 well or nonionic dispersant, emulsifier, , wetting agent - with at least one. (Priority 08/02/83) 2. The herbicide according to claim 1, characterized in that it contains an active ingredient of the formula (I) in which X), X ₂ and Y are (a) methyl, methyl and pyrazol-1-yl; methyl Or (b) methyl, methyl and ethoxymethyl groups. (Priority: 2/9/1982) 3. A herbicide composition as claimed in claim 1, wherein said formula (I), contains ₄ c our being active, wherein X 1, X ₂ and Y are (a) methyl, methyl and 1- (pyrazol-1-yl) ethyl, respectively; (B) methyl, methyl and n-propoxymethyl; (c) methyl, ethyl and ethoxymethyl; (d) methyl, methoxy and pyrazol-1-ylmethyl; (e) methyl, methoxy and 1-ethoxyethyl. 55 (Priority: 9/9/1982) The herbicide according to claim 1, characterized in that it contains an active ingredient of the formula I in which X and X _{2 are} methyl and Y is 1-methoxy-2-methylqq-ethyl. (Priority: September 13, 1982) The herbicide according to claim 1, characterized in that it contains an active ingredient of the formula I in which X (and X _{2 are} methyl, Y 2-methyl-1,3,4-1H-tri65 azol-5-yl). Group (Priority: 08/02/83) -22193036 A process for the preparation of the chloroacetamide derivatives of the formula (I): wherein: X and X ₂ are independently C 1 -C 4 alkyl, C 5 -C 4 alkylthio, C 1 -C 4 alkoxy, C 1 -C 4 alkylsulfinyl, C 2 -C 4 alkanoyl C [= = NO (C1-C4 alkyl)] - (C1-C3 alkyl), C [O (C1-C4 alkyl)] _2- (C1-C3 alkyl) or (C1-C5 alkyl) alkoxy) carbonyl group; X and X ₂ may each be hydrogen; 15 Z is -NH- or CZ, a group of formula, and when Z is NH, X i and X ₂ C 1-4 alkyl; Z, hydrogen, halogen, C 1 -C 4 alkyl, or C 1 -C 4 alkoxy-carbonyl, Y (a) C 1 -C 4 alkyl, C 3 -C 5 haloalkenyl C3-C5 alkynyl, C1-C4 haloalkyl, or benzyl; or (b) -CHfRJ-COY; R, hydrogen or C 1-4 alkyl and Y, hydroxy, C 1-4 alkoxy, C 3-5 alkynyloxy, C 1-4 alkylamino, di (C 1-4 alkyl) - amino - or -NH-N = C (l-3 alkyl) ₂ -group or (c) _z -R ₂ -A a group of formula, and 40 in the group R ₂ -CH ₂ - or -CH ₂ - CH ₂ which is unsubstituted or substituted with C 1-5 alkyl and Furyl, thienyl, thiazolyl monosubstituted with 1-pyrazolyl, 3,5-dimethyl-1-pyrazolyl, 1,2,4-triazolyl, 2-pyrimidinyl or optionally monosubstituted with C 1-4 alkyl; -, isoxazolyl, 1,3,4-thiadiazolyl or tetrahydrofuryl or 1,3,4,4-mono- or disubstituted with C 1-4 -alkyl and / or C 1-4 -alkylthio. -triazolyl or (d) -AOR ₃ and in this group R _{3 is} hydrogen or C 1-4 alkyl, which may be substituted by halogen, cyano or C 1-4 alkoxy, C 1-4 alkyl optionally substituted with C 1 -C 4 alkoxy, which may be attached to R _{3 to} form a 1,3-dioxolane ring, wherein the nitrogen and oxygen to which A is attached are separated by up to 3 carbon atoms; or (e) -CH-C = NOR; Ϊ _R5 ^k! 5 ports in which R _{4 is C} 1-4 alkyl, R ₅ and R ₃ are independently hydrogen or methyl, - characterized in that ^a) a (Π) compound of formula X ,, X _2, Z and Y are as defined above - to N-acetyl group hydroxyl replace chlorine Who; b) a compound of formula (III) - X, X ₂ and Z as defined above - a compound of formula (IV) - Y having the meaning given above and L being N-alkylation reaction conditions, preferably chlorine or bromine, methanesulfonyloxy; or p-toluenesulfonyloxy; c) for the preparation of compounds of formula Ia in the formula R 'is hydrogen or C 1-3 alkyl, Y _{2 is} ', -OR ₃ , or N-methyl-N-acetylamino and The 'di- or triazole ring, which is attached to one of its nitrogen atoms by the -CHR' group; X ,, X _2, and Z and R ₃ are as defined above (V) compound - X ,, X _2, Z and R 'are as defined above - with a compound (VI) - Y ₂ are as defined above - reacting a reactive derivative with a trialkylsilyl derivative; d) N-acylating a compound of formula VII, X, X ₂ , Z and Y as defined above, with chloroacetyl chloride. (Priority 08/02/83) 7. Process according to claim 1, wherein the hydroxyl group of the N-hydroxyacetyl group in the compound of the formula II is reacted with a chlorinating agent, preferably thionichloride, or the compound of the formula II with a sulfonyl halide. and then exchanging the resulting sulfonyloxy ester with a chlorine anion nucleophilic reagent, preferably tetrabutylammonium chloride. (Priority: 08/02/1983)