HRP940868A2 - Certain 2-(2-substituted benzoyl)-4-(substituted oxy or substituted thio)-1,3,cyclohexanendiones - Google Patents

Description

The field of technology

The invention is from the field of organic and phytopharmaceutical chemistry.

Technical problem

This invention relates to 2-(2-substituted benzoyl)-4-(substituted oxy or substituted thio)-1,3-cyclohexanediones and their use as herbicides.

State of the art

This application is a continuation of application serial number 919,280, filed October 16, 1986.

European patent applications no. 135.191; 186.118; 186.119 and 186.120 refer to some herbicidal compounds which may have the following structural formula

[image]

where R to R 5 , R 7 and R 8 are as defined below and Ra is C 1-4 alkyl.

Description of the solution to the technical problem with implementation examples

One subject of this invention is a herbicidal preparation containing herbicidally active 2-(2-substituted benzoyl)-4-(substituted oxy or substituted thio)-1,3-cyclohexanedione and an inert carrier. The 5- and 6-positions of the 1,3-cyclohexanedione moiety are preferably substituted with groups defined below, most preferably with hydrogen or methyl groups. The substituted benzoyl and cyclohexanedione moieties may be further substituted with the groups listed below.

Also subject to the scope of this invention are novel compounds having the following structural formula

[image]

where X is oxy, thio, sulfinyl or sulfonyl;

R is halogen, preferably chlorine or bromine; C1-2alkyl, preferably methyl; C1-2Alkoxy, preferably methoxy; trifluoromethoxy; difluoromethoxy; nitro; cyano; C1-2haloalkyl, preferably trifluoromethyl; RaSOn - where n is 0 or 2, preferably 2 and Ra is C1-2alkyl preferably methyl, trifluoromethyl or difluoromethyl. Preferably chlorine, nitro, methyl, trifluoromethyl or methylsulfonyl;

R 1 is hydrogen; C1-4alkyl, preferably methyl; phenyl; or substituted phenyl;

R 2 is hydrogen or C 1-4 alkyl, preferably methyl, or

R 1 and R 2 together are C 2-5 alkylene;

R 3 is hydrogen; C1-4alkyl, preferably methyl; phenyl; or substituted phenyl with the restriction that R 1 and R 3 are not both phenyl or substituted phenyl;

R4 is hydrogen or C1-4alkyl, preferably methyl

R5 is hydrogen or C1-4alkyl, preferably methyl

R 6 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl or phenyl and

R7 and R8 are independent

(1) hydrogen;

(2) halogen, preferably chlorine, fluorine or bromine;

(3) C 1-4 alkyl, preferably methyl;

(4) C1-4Alkoxy, preferably methoxy;

(5) trifluoromethoxy

(6) cyano;

(7) nitro;

(8) C1-4haloalkyl, preferably trifluoromethyl;

(9) RbSOn- where n is an integer of 0, 1 or 2, preferably 2; and

R b is (a) C 1-4 alkyl, preferably methyl;

(b) C 1-4 alkyl substituted with halogen or cyano, preferably chloromethyl, trifluoromethyl or cyanomethyl;

(c) phenyl; or

(d) benzyl;

(10) -NRcRd where Rc and Rd are independently hydrogen or C1-4alkyl;

(11) ReC(O)- where Re is C1-4 alkyl or C1-4 alkoxy;

(12) -SO2NRcRd where Rc and Rd are as defined; or

(13) -N(Rc)C(O)Rd where Rc and Rd are as defined.

Preferably R7 is in the 3-position. More preferably, R 7 - is hydrogen, chlorine, fluorine, trifluoromethyl, cyano, C 1-4 alkoxy or C 1-4 thioalkyl. Most preferably, R7 is hydrogen. Preferably R8 is in 4-position. Most preferably R8 is halogen, cyano, trifluoromethyl or RbSO2 where Rb is C1-4alkyl, preferably methyl or C1-4haloalkyl, preferably chloromethyl, difluoromethyl or trifluoromethyl.

The term "C 1-4 alkyl" includes methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl and t-butyl. The term "halogen" includes chlorine, bromine, iodine and fluorine. The term "C 1-4 alkoxy" includes methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy and t-butoxy. The term "C1-4haloalkyl" includes the alkyl groups defined above under C1-4alkyl in which one or more hydrogens have been replaced by chlorine, bromine, iodine or fluorine.

Salts of the compounds described above (as defined below) are included within the scope of this invention.

The compounds of this invention have the following four structural formulas due to tautomerism:

[image]

where R, R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined above.

The circling proton on each of the four tautomers is understandably labile. These protons are acidic and can be removed by reacting with a base to form a salt whose anion has the following four resonance forms:

[image]

where R, R1, R2, R3, R4, R5, R6, R7, R8 and X are as defined above.

Examples of cations of these bases are inorganic cations such as alkali metals, eg lithium, sodium and potassium; alkaline earth metals, eg calcium, magnesium or ammonium or organic cations such as substituted ammonium, sulfonium, sulfoxonium or phosphonium where the substituents are aliphatic or aromatic groups.

It will be appreciated by those skilled in the art to consider that salts of the present invention with varying degrees of anion to cation will exist depending on the nature of the cation. In some cases with a suitable cation, such as copper, it can exist in a chelated form.

The compounds of this invention and their salts are active herbicides of general type. That is, they are herbicidally effective against a wide range of plant species. The process of controlling unwanted vegetation of the present invention comprises the application of a herbicidally effective amount of the above-described compounds or their salts to the surface to be controlled.

The compounds of this invention can be prepared by the following two- or, if necessary, three-step general procedure.

The process proceeds via the production of an enol ester intermediate as shown in reaction (1). The final product is obtained by displacement of the enol ester as shown in reaction (2) or, if necessary, by subsequent oxidation of the product obtained in step (2) as shown in reaction (3).

The procedure is carried out in the presence of a catalytic amount of a source of cyanide anion and/or hydrogen cyanide, together with a molar excess, with respect to the enol ester, of a moderate base.

Both reactions can be performed as separate steps by isolating and extracting the enol ester using common techniques before performing step (2), or by adding a cyanide source to the reaction medium after the enol ester is built, or in one step by including a cyanide source at the beginning of the reaction (1).

[image]

wherein R to R8 and X and a moderate base are as defined and Y is halogen, preferably chlorine, C1-4alkyl-C(O)-O-, C1-4alkyloxy-C(O)-O- or

[image]

where R, R7 and R8 in this part of the molecule are identical to those in the reactant shown above and the moderate base is as defined, preferably tri-C1-6alkylamine, alkali metal carbonate or alkali metal phosphate.

Generally, in step (1) molar amounts of the dione and substituted benzoyl reactant are used, together with a molar amount or excess of base. Both reactants are combined in an organic solvent such as methylene chloride, toluene, ethyl acetate or dimethylformamide. A base or benzoyl reactant is preferably added to the reaction mixture for cooling. The mixture is stirred at 0 - 50°C until the reaction is completed.

[image]

where the moderate base and R to R8 and X are as defined above.

Generally, in step (2) a mole of the enol ester intermediate is reacted with 1 to 4 moles of a moderate base, preferably about 2 moles of a moderate base and from 0.01 mole to about 0.5 mole or more, preferably about 0.01 - 0.1 mol of cyanide source. The mixture is stirred in the reactor until the reaction is substantially complete at a temperature below 50°C, preferably about 20 to about 40°C, and the resulting product is isolated by conventional techniques.

Alternatively, some compounds of this invention can be prepared by the following reaction

[image]

where R to R8 are as defined, m is an integer of 1 or 2 and /O/ is an oxidizing agent, preferably a peroxide such as peracetic acid or m-chloroperbenzoic acid.

Generally, in reaction step (3) the substituted moiety is dissolved in methylene chloride and an oxidizing agent such as m-chloroperbenzoic acid (1.1 or 2.2 equivalents) is added in portions, and the reaction mixture is stirred for 1 to 8 hours. The product can be isolated using conventional techniques.

The term "cyanide source" means a substance or substances which, under conditions of transfer, contain or generate hydrogen cyanide and/or cyanide anion.

Preferred sources of cyanide are alkali metal cyanides such as sodium or potassium cyanide; methyl alkyl ketone cyanohydrins having 1-4 carbon atoms in the alkyl groups, such as acetone or methyl isobutyl ketone cyanohydrins; benzaldehyde cyanohydrin; cyanohydrins of C2-5 aliphatic aldehydes such as acetaldehyde cyanohydrin, propionalaldehyde cyanohydrin, etc.; cyclohexanone cyanohydrin; lactonitrile; zinc cyanide; di- and tri-(lower alkyl)silylcyanides; known dimethyl- and trimethylsilyl cyanide; potassium tery cyanide; and hydrogen cyanide itself. Hydrogen cyanide is the most preferred because it gives a very fast reaction and is not expensive. Among cyanohydrins, the preferred source of cyanide is acetone cyanohydrin.

The cyanide source is used in an amount of up to about 50 mole % in relation to the enol ester. As little as about 1 mole percent can be used to achieve an acceptable reaction rate at about 40°C at a smaller scale of production. In larger-scale reactions, it gives more reproducible results with slightly higher catalytic amounts of about 2 mol.%. In general, about 1 - 10 mol.% of the cyanide source is preferred.

The procedure is carried out with a small molar excess, considering the enol ester, moderate base. The term "moderate base" means a substance that acts as a base and whose activity as a base lies between that of strong bases such as hydroxides (which can cause hydrolysis of enol esters) and that of weak bases such as N,N-dimethylaniline (which will not act effectively ). Moderate bases suitable for use in the invention include organic, eg trialkyl amines such as triethylamine and inorganic bases such as alkali metal carbonates and phosphates. Suitable inorganic bases include potassium carbonate and trisodium phosphate.

The base is used in an amount of about 1 to about 4 moles per mole. of enol ester, preferably about 2 mol per mol.

When the source is alkali metal cyanide cyanide, especially potassium cyanide, a phase transfer catalyst may be included in the reaction. Particularly suitable phase transfer catalysts are chromium ethers.

A number of different solvents are applicable in this process, depending on the nature of the halogen acid or the acylated product. The preferred solvent for this reaction is 1,2-dichloroethane. Other solvents that may be used, depending on the reactants or products, include toluene, acetonitrile, methylene chloride, ethyl acetate, dimethylformamide, and methyl isobutyl ketone (MIBK).

In general, depending on the nature of the reactants and the source of cyanide, the transfer can be carried out at temperatures up to about 50°C.

The substituted benzoyl chlorides described above can be prepared from the corresponding substituted benzoic acids according to Reagents for Organic Synthesis. vol 1, L.F. Fieser and M. Fieser p. 767-769 (1967).

[image]

where R, R7 and R8 are as previously defined.

Substituted benzoic acids can be prepared by a number of different methods according to The Chemistry of Carboxylic Acids and Esters, S. Patai, J. Wiley and Sons, New York, N.Y. (1969) and Survey of Organic Synthesis, C. A. Buehler and D. F. Pearson, J. Wiley and Sons (1970).

The following are three representative examples of the methods described here.

[image]

where R, R7 and R8 are as previously defined.

In reaction (a), the substituted benzonitrile was heated at reflux in aqueous sulfuric acid for several hours. The mixture was cooled and the reaction product was isolated by conventional techniques.

[image]

where R, R7 and R8 are as previously defined.

In reaction (b), the substituted acetophenone was heated at reflux for several hours in an aqueous hypochlorite solution. The mixture was cooled and the reaction product was isolated by conventional techniques.

[image]

where R, R7 and R8 are as previously defined.

In reaction (c), the substituted toluene is heated at reflux in an aqueous solution of potassium permanganate for several hours. The solution is then filtered and the reaction product is isolated by conventional techniques.

Substituted 1,3-cyclohexanediones can be obtained using a number of known methods according to Modern Synthetic Reactions, 2nd Edition, Chapter 9, H.O. House, W.A. Benjamin, Inc. Menlo Park, CA (1972).

The following examples illustrate the syntheses of a representative compound of this invention.

Example 1

4-methylthiocyclohexane-1,3-dione

[image]

1-(Methylthio)-2-propanone (25 grams (g), 0.24 mol), ethyl acrylate (24g, 0.24 mol) and benzyltrimethylammonium methoxide /2 milliliters (ml) of a 40 wt.% solution in methanol/ is dissolved in toluene (100 ml). A solution of sodium methoxide (77.8g, 25 wt.% in methanol, 0.36 mol) was then added to the solution dropwise at a rate such that the temperature was maintained below 35°C. After stirring for an additional two hours at room temperature, the reaction mixture was poured into 200 ml of ice water and extracted with 100 ml of ether. The aqueous phase was acidified with 2M hydrochloric acid and extracted with ether. The ether layer was dried over magnesium sulfate, filtered and concentrated under vacuum to give 23.1 g of oil. The oil was dissolved in benzene (100 ml) and the desired product slowly separated out of solution as waxy crystals (9.8 g).

Example 2.

2-(2-chloro-4-methylsulfonylbenzoyl)-4-methylthiocyclohexane-1,3-dione

[image]

4-Methylthiocyclohexane-1,3-dione (4.4 grams, 28 mL) and 2-chloro-4-methylsulfonylbenzoyl chloride (7.7 g, 28 mmol) were dissolved in 75 mL of methylene chloride at room temperature. Triethylamine (5.6g, 56 mmol) was added slowly with cooling. The reaction mixture was stirred at room temperature for 5 hours and then poured into 2M hydrochloric acid. The aqueous phase was discarded and the organic phase was dried over magnesium sulfate and then evaporated under vacuum to give the intermediate enol ester. The enol ester was dissolved in 75 ml of acetonitrile and triethylamine (5.6 g, 56 mmol) was added at once, followed by the addition of acetocyanohydrin (0.8 g, 10 mmol). The reaction mixture was stirred at room temperature for 1 hour and then partitioned between 1 M hydrochloric acid (100 ml) and ethyl ether (200 ml). The ether layer was washed with water and the product was recrystallized from solution on standing. Filtration of the mixture gives 3.6 g of the desired product with m.p. 146-149°C.

Example 3.

2-(2-chloro-4-methylsulfonyl-benzoyl)-4-methylsulfonylcyclohexane-1,3-dione

[image]

2-(2-Chloro-4-methylsulfonylbenzoyl)-4-methylthiocyclohexane-1,3-dione (1.9g, 5mmol) was dissolved in methylene chloride (20ml). Meta-chlorobenzoic acid (85%, 2.0 g, 10 mmol) was added portionwise to the stirred solution at room temperature over 10 minutes. The reaction mixture was stirred at room temperature for 2 hours and then cooled to 5°C with an ice bath. The precipitated m-chlorobenzoic acid was removed by filtration and the product obtained by concentration was filtered in vacuo. The desired product (2 g) was obtained as a dark brown solid with m.p. from 175-180°C.

The following is a Table with selected compounds obtained according to the procedure described here. The connection numbers given to each connection are also used in the further part of the application.

Table I

[image]

[image] [image] [image]

(a) obtained in Example 2

(b) obtained in Example 3

(c) as thiethyl amine salt

(d) as the sodium salt

(e) as copper chelate

Herbicide test trials

As previously mentioned, the compounds described herein obtained in the manner described above are phytotoxic compounds that are applicable and valuable in controlling various plant species. Selected compounds of this invention were tested as herbicides in the following manner.

Pre-emergence herbicide test.

On the day before treatment, seeds of seven different weed species were sown in loamy sandy soil in separate rows using one species per bed. The seeds used were green foxtail (FT) (Seraria viridis), water grass (WG) (Echinochloa crusgalli), wild oats (WO) (Avena fatua), annual sedge (AMG) (Ipomoea lacunosa), velvet (VL) (Abutilon theophrast), Indian salt (MD) (Brassica juncea), and yellow walnut blade (YNG) (Cyperus esculentus). Enough seeds were planted to produce 20 to 40 seedlings per bed, after germination, depending on the size of the plants.

Using an analytical balance, 600 mg of the test compound was weighed onto a piece of glassy weighing paper. The paper and compound were placed in a 60 ml clean bottle. with a wide neck and were dissolved in 45 ml of acetone or some other solvent. 18 ml of this solution was transferred to a clean 60 ml bottle with a wide mouth and diluted with 22 ml of a mixture of water and acetone (19:1) containing enough sorbitan monolaurate emulsifier to give a final solution of 0.5% (v/v ). The solution was then sprayed onto the seeded area on a linear spray table calibrated to give 748 I/ha. The rate of application is 4.48 kg/ha.

After treatment, the sown plants were placed in a greenhouse at a temperature of 21 to 26.5°C and watered by spraying. Two weeks after treatment, the degree of damage or control was determined by comparing with untreated plants of the same age. Damage from 0 to 100% was determined for each species as a percentage of control with 0% representing no damage and 100% representing complete control.

The test results are shown in the following Table II.

Table II

Preemergence herbicidal activity

rate of application – 4.48 kg/ha

[image] [image]

Herbicide test after emergence.

This test was performed identically to the pre-emergence herbicidal activity test, with the exception that seeds of seven different weed species were sown 10-12 days prior to treatment. Also, irrigation of the treated areas was carried out on the surface of the land and not on the leaves of the developed plants.

The results of the herbicide test after emergence are given in Table III.

Table III

Preemergence herbicidal activity

rate of application – 4.48 kg/ha

[image] [image]

The compounds of this invention and their salts are useful as herbicides and can be applied in different ways at different concentrations. In practice, compounds or salts are formulated into herbicidal preparations, by mixing, in herbicidally effective amounts, with additives and carriers normally usable to facilitate the dispersion of active ingredients for use in agriculture, taking into account the fact that the formulation and method of application of the toxicant can affect the activity of the material in a given application. Thus, these active herbicidal compounds or salts may be formulated as relatively large particle size granules, as wettable powders, as liquids, as solutions, or as any of a number of other known types of formulation, depending on the desired route of administration. These formulations may contain from about 0.5% to about 95% by weight or more of active ingredients. The herbicidally effective amount depends on the nature of the seed or plants being controlled and the rate of application which varies from about 0.0112 kg/ha to about 11.2 kg/ha, preferably from about 0.0224 to about 4.48 kg/ha.

Wettable powders are in the form of finely divided particles that are easily dispersed in water or other dispersants. The wettable powder is ultimately applied to the land as a dry powder or as a dispersion in water or another liquid. Typical carriers for wettable powders include rolling loam, kaolin clays, silicates, and other easily wettable organic or inorganic diluents. Wettable powders are normally formulated to contain about 5% to about 95% of the active ingredient and usually also contain a small amount of wetting, dispersing or emulsifying agent to aid in wetting and dispersion.

Emulsifying concentrates are homogeneous liquid preparations that are dispersed in water or other dispersants, and may contain a fully active compound or salt with a liquid or solid emulsifying agent, or may also contain a liquid carrier such as xylene, heavy aromatic naphthol, isophorone and others -volatile organic solvents. For herbicidal application, these concentrates are dispersed in water or other liquid carriers and normally applied as a spray to the surface to be treated. The mass percentage of the essentially active ingredient can vary according to the way the preparation is applied, but in general it comprises about 0.5% to 95% of the active ingredient from the mass of the herbicidal preparation.

Granular formations, where the toxicant is applied on relatively coarse particles, are usually applied without dilution to the surface where vegetation is to be controlled. Typical carriers for granular formulations include rolled earth, attapulgite clay, bentonite clay, montmorillonite clay, vermiculite, perlite, and other organic or inorganic materials that adsorb or may be coated with the toxicant. Granular formulations are normally prepared to contain up to about 25% active ingredients and may contain surfactants such as heavy aromatic naphtha, kerosene or other petroleum fractions, or vegetable oils; and/or such as destrins, glue or synthetic resin.

Typical wetting, dispersing or emulsifying agents used in agricultural formulations include, for example, alkyl and alkylaryl sulfonates and sulfates and salts thereof; polyhydroxyl alcohols; esters and fatty amines; and other types of surfactants, many of which are commercially available. Surfactants, when used, normally comprise from 0.1% to 15% of the mass of the herbicide preparation.

Powders, which are free-flowing mixtures of the active ingredient with finely divided solid particles such as talc, clay, flour and other organic and inorganic solids that act as dispersants and carriers for the toxicant, are applicable formulations for application by injecting into the soil.

Pastes, which are homogeneous suspensions of finely ground solid toxicant in a liquid carrier such as water or oil, are used for specific purposes. These formulations normally contain about 5% to about 95% by weight of the active ingredient and may also contain small amounts of wetting, dispersing or emulsifying agents to facilitate dispersion. For application, the pastes are normally diluted and applied as a spray to the surface to be treated.

Other applicable formulations for herbicidal applications include simple solutions of the active ingredient in a dispersant in which it is completely dissolved at the desired concentration, such as acetone, alkylated naphthalenes, xylene and other organic solvents. Pressurized sprays, typically aerosols, where the active ingredient is dispersed in finely divided form as a result of evaporation of a low-boiling dispersing solvent, such as freons, may also be used.

Phytotoxic preparations of the present invention can be applied to plants in a conventional manner. Thus, powder and liquid preparations can be applied using a powerful sprayer, explosive or hand sprayer and powder sprayer.

The preparations can also be applied from the plane as a powder or spray because they are effective in very small doses. In order to modify or control germinating seeds or sprouted seedlings, as a typical example, powder and liquid preparations can be applied to the soil by conventional methods and can be distributed into the soil to a depth of at least 1.33 cm below the soil surface. It is not necessary for phytotoxic preparations to be mechanically mixed with soil particles and these preparations can be applied mainly by spraying or spraying the soil surface. The phytotoxic preparations of this invention can also be applied by adding them to the irrigation water supplied to the fields to be treated. This method of application allows the penetration of the preparation into the soil as water that has adsorbed it. Powder preparations and granular preparations or liquid formulations applied to the soil surface may be distributed below the soil surface by conventional methods such as rolling, trailing or mixing procedures. In the following examples, the herbicidal compounds can be substituted with a salt of the herbicidal compound.

Formulations of emulsion concentrates

[image]

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[image]

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When salts are used as an active ingredient in the herbicidal preparations of this invention, it is advisable to use salts that are acceptable in agriculture.

The phytotoxic preparations of the present invention may also contain other additives, for example, fertilizers, other herbicides and other pesticides, used as additives or in combination with some other additives given above. Fertilizers applicable in combination with active ingredients include, for example, ammonium nitrate, urea, superphosphate.

Claims (3)

1. Procedure for obtaining a compound of the formula [image] where X is oxy, thio, sulfinyl or sulfonyl; R is halogen; C1-2 alkyl; C1-2Alkoxy; trifluoromethoxy; difluoromethoxy; nitro, cyano; C1-2haloalkyl; RaSOn- where n is 0 or 2 and Ra is C1-2alkyl, trifluoromethyl or difluoromethyl; R 1 is hydrogen, C 1-4 alkyl, phenyl or substituted phenyl; R 2 is hydrogen or C 1-4 alkyl; or R 1 and R 2 together are C 1-5 alkylene; R 3 is hydrogen, C 1-4 alkyl, phenyl or substituted phenyl with the limitation that R 1 and R 3 are not both phenyl or substituted phenyl; R 4 is hydrogen or C 1-4 alkyl; R 5 is hydrogen or C 1-4 alkyl; R 6 is hydrogen, C 1-4 alkyl, C 1-4 haloalkyl or phenyl; R7 and R8 are independent (1) hydrogen; (2) halogen; (3) C 1-4 alkyl; (4) Alkoxy; (5) trifluoromethoxy; (6) cyano; (7) nitro; (8) C1-4haloalkyl; (9) RbSOn- where n is an integer 0, 1 or 2; and Rb is (a) C 1-4 alkyl; (b) C 1-4 alkyl substituted with halogen or cyano; (c) phenyl; or (d) benzyl; (1) -NRcRd where Rc and Rd are independently hydrogen or C1-4alkyl; (2) ReC(O)- where Re is C 1-4 alkyl or C 1-4 alkoxy; or (3) -SO2NRcRd where Rc and Rd are as defined; and (4) -N(Rc)C(O)Rd where Rc and Rd are as defined, characterized by the fact that it includes the reacting part of the formula [image] where R 1 to R 6 and X are as defined in , with a substituted benzene reactant of the formula [image] where R, R 7 and R 8 are as defined and Y is halogen, C 1-4 alkyl-C(O)-O-, C 1-4 alkoxy-C(O)-O- or [image] where R, R7 and R8 in this part of the molecule are identical to those in the reactant shown above with at least one mole of moderate base so that the intermediate enol ester of the formula is built [image] where R to R8 and X are as defined above, which is reacted with 1 to 4 moles of a moderate base and from 0.01 mole or more of a cyanide source to form a compound of the formula [image] where R1 to R8 and X are as defined above. 2. The process according to claim 1, characterized in that X is halogen, the moderate base is tri-C1-6 alkylamine, pyridine, carbonate or alkali metal phosphate and the source of cyanide is alkali metal cyanide, methyl C1-4 alkyl ketone cyanohydrins, benzaldehyde or C2 cyanohydrins -5aliphatic aldehydes; cyanohydrins, zinc cyanide; tri(lower alkyl)silyl cyanide or hydrogen cyanide. 3. The method according to claim 2, characterized in that X is chlorine, the moderate base is tri-C1-6 alkylamine, pyridine, sodium carbonate or sodium phosphate and the source of cyanide is potassium cyanide, acetone cyanohydrin or hydrogen cyanide.