Method for the stereoselective production of Z-1,2-diaryl-alkyl-chlorides and their conversion to azolylmethyloxiranes as well as intermediates.

The present invention relates to the stereoselective preparation of Z-1,2-diaryl-allyl chlorides of the general formula I.<chemistry id="chem0001" num="0001"><img file="EP0409049A2_D0001.tif" /></chemistry>in which the residues R¹ and R² independently of one another are hydrogen, halogen, alkyl, haloalkyl, alkoxy, haloalkoxy or an unsubstituted or substituted aromatic radical and n and m are 1, 2 or 3.

The invention further relates to the conversion of the Z-1,2-diaryl-allyl chlorides to azolylmethyloxiranes of the formula IV<chemistry id="chem0002" num="0002"><img file="EP0409049A2_D0002.tif" /></chemistry>in which the remains (R¹)_n, (R²)_" have the meaning given above and X represents CH or N.

The new intermediates I and the resulting epoxidation products V are also the subject of the invention.

Compounds of structure type I are valuable intermediates for the production of pharmacological, fungicidal and antifungal agents in accordance with German Offenlegungsschriften 32 18 129 and 32 18 130 as well as in EP-A 196 038 and US-A-3 422 153. So far, they have been obtained by radical halogenation of corresponding diarylpropene compounds (DE-A 32 18 129 or EP-A 196 038) or by oxidation and subsequent substitution (DE-A 32 18 130). The disadvantages of the methods of the prior art are the use of expensive reagents, for example expensive halogenation reagents such as N-bromosuccinimide for radical bromination, the number of synthesis steps and in particular the low stereoselectivity.

It is generally known that molecules which have a specific biological or pharmacological action must in many cases have defined geometrical arrangements of certain functional groups. In the case of the fungicidal active compounds of the general formula III or IV (see DE-A 26 52 313), it is primarily the Z-configured compounds (cf. sequence rule according to Cahn, Ingold, Prelog), ie the compounds in which the optionally substituted phenyl radicals are trans to one another, which have a particularly high activity as crop protection agents.

The invention was therefore based on the object of finding a process by which the intermediates I can be prepared in as isomerically pure form as possible, ie with high preference for the E or trans configuration of the phenyl radicals on the double bond and in high yield. It was also an object to use advantageous intermediates to find a production process for the fungicidal azolylmethyloxiranes IV which is distinguished by high overall yields and by a shorter number of reaction steps compared to the processes described in DE-A 32 18 129 and 32 18 130 .

According to the prior art, aryl-substituted alcohols can be converted under acidic reaction conditions, for example using sulfuric acid in the organic phase, into the corresponding aryl-substituted olefins or styrenes (see, for example, Houben-Weyl, Methods of Organic Chemistry, 4th Edition Volume 5/1 b -Alkenes, cycloalkenes, arylalkenes, Georg Thieme Verlag Stuttgart, 1972, pp. 62 ff, in particular pp. 70 and 71; Tetrahedron, volume 26, pp. 4277ff (1970).

It is also known that such reactions can be carried out with the aid of water-absorbing reagents such as acetic anhydride. However, higher reaction temperatures are generally necessary for these elimination reactions described in the literature. Under such reaction conditions, insufficient EZ isomer ratios with respect to the aryl-aryl arrangement are obtained.

It has now become a process for the stereoselective preparation of Z-1,2-diaryl-allyl chlorides of the general formula I<chemistry id="chem0003" num="0003"><img file="EP0409049A2_D0003.tif" /></chemistry>in which the residues R¹ and R² independently of one another denote hydrogen, halogen, alkyl, haloalkyl alkoxy, haloalkoxy or a substituted aromatic radical and n and m represent 1, 2 or 3, which is characterized in that chlorohydrins of the formula 11<chemistry id="chem0004" num="0004"><img file="EP0409049A2_D0004.tif" /></chemistry>in which the radicals have the abovementioned meaning, dehydrated in an inert ether or carboxylic acid ester as solvent in the presence of a carboxylic acid anhydride and an organic or inorganic acid at temperatures up to 50 ° C.

Z-configured 1,2-diarylallyl chlorides can be obtained with high stereoselectivity by the process according to the invention. In general, and in particular according to the preferred embodiments of the method, the Z: E ratios are 8: 1 to 15: 1. The high regioselectivity with which the elimination of water takes place is also surprising, since one would have expected a dehydration in the direction of the chloromethyl side chain to chlorovinyldiaryl compounds to a greater extent as a side reaction. Furthermore, expected competitive reactions such as substitution instead of elimination can be successfully suppressed. Likewise, there is practically no expected acylation of the alcohol function.

The chlorohydrins of the general formula II are generally known and can be prepared, for example according to DE-A 28 51 086, EP-A 47 594 or EP-A 15 757, in good yields by adding benzyl Grignard compounds VI to ω-chloroacetophenones VII in accordance with the following reaction scheme become:<chemistry id="chem0005" num="0005"><img file="EP0409049A2_D0005.tif" /></chemistry>

With regard to the production process of the Z-allyl chloride, it is also advantageous to first prepare the chlorohydrins in diethyl ether and by adding anorg. Acid, such as conc. Sulfuric acid and carboxylic anhydride to the diethyl ether solution at about -10 to 0 ° C to carry out the dehydration in the sense of a one-pot process.

It is also possible, instead of an aqueous work-up in the synthesis of chlorohydrin, to release the chlorohydrin from the magnesium alkoxylate precursor by adding equimolar amounts of acid, for example sulfuric acid, and then to carry out the dehydration.

Advantageous and according to the invention is the gradual metering in of carboxylic acid anhydride, the O-acylation of chlorohydrin compared to the dehydration being largely suppressed.

The dehydration of chlorohydrins II according to the invention takes place in an ether or ester as solvent. In the case of open-chain ethers, those having at least 2 oxygen atoms, such as ethers of glycols and low-molecular aliphatic alcohols, for example ethylene glycol dimethyl or diethyl ether, are preferred. Cyclic ethers such as tetrahydrofuran (THF) and especially dioxane are particularly advantageous. Small additions of aprotic solvents such as ethyl acetate, halogenated hydrocarbons such as methylene chloride or THF, for example to dioxane as solvents, can be added for better solvolysis at low temperatures, for example below about 10 ° C.

Esters which are particularly suitable for the process according to the invention are esters of low molecular weight aliphatic carboxylic acids, in particular monocarboxylic acids, and low molecular weight aliphatic alcohols, the term low molecular weight meaning each containing about 1 to 6 carbon atoms. For example, the following esters are listed: ethyl acetate, ethyl formate, methyl propionate, methyl butyrate, methyl or ethyl isobutyrate, with ethyl acetate being preferred.

The amounts of solvent are not particularly critical and can be varied within wide limits. They are generally about 1 to 50% by weight, in particular 2.5 to 10% by weight, based on the chlorohydrin 11. Higher excesses of solvent are quite possible, and mixtures of those mentioned, for example, in claims 1 to 5 can also be used Solvents are used for the dehydration, the mixing ratios being able to be varied within a wide range from approximately 10: 1 to 1:10. To achieve higher space-time yields and high Z product fractions, additions of 5 to 20% by weight, based on dioxane, have proven effective.

A carboxylic anhydride is added to the reaction mixture as a water-absorbing agent. Anhydrides of aliphatic low molecular weight monocarboxylic acids such as acetic anhydride, propionic anhydride, butyric anhydride and isobutyric anhydride are particularly suitable. However, anhydrides of aliphatic or aromatic dicarboxylic acids such as malonic anhydride, maleic anhydride, succinic anhydride or phthalic anhydride can also be present.

0.5 to 3, in particular 1 to 2, molar equivalents of anhydride, based on the chlorohydrin II, are generally used for the dehydration. Larger quantities are possible, but have no further advantages.

Particularly advantageous results are obtained with a combination of dioxane and / or THF as the solvent with acetic anhydride and sulfuric acid or with the use of ethyl acetate as the solvent with isobutyric anhydride and sulfuric acid.

The dehydration is carried out under acidic reaction conditions, using customary acids, for example organic sulfonic acids such as trifluoromethanesulfonic acid, methanesulfonic acid, para-toluenesulfonic acid or naphthalenesulfonic acid and in particular concentrated mineral acids such as perchloric acid, phosphoric acid and in particular sulfuric acid of 30 to 99.9%, preferably 50 to 99 or Oleum. When using more water-containing acids, more carboxylic anhydride is generally used.

The acid can be used in a catalytic, in a stoichiometric amount or in excess, based on II. Amounts of approximately 0.01 to 4 molar equivalents, based on 11, are preferred. If oleum is used, smaller amounts of 0.05 to 1 molar equivalents, based on 11, are advantageous.

An advantageous variant of the process according to the invention is that instead of the carboxylic anhydride as the water-absorbing agent, ketene is used, optionally in combination with stoichiometric or catalytic amounts of an aliphatic carboxylic acid, based on II. In this case, the carboxylic acid, for example one of the low-molecular aliphatic carboxylic acids listed above, and the gaseous ketene is added to the reaction mixture or the ketene is added in gaseous form to the chlorohydrin II dissolved in the solvent without addition of carboxylic acid. The amount of ketene corresponds to the amounts given above for the carboxylic anhydride.

In order to achieve high Z isomer proportions, the dehydration should be carried out at temperatures as low as possible, ie temperatures up to about 50 ° C., advantageously -25 to + 40 ° C., in particular -25 to + 30 ° C.

As a rule, the dehydration is carried out at normal pressure. A reaction under vacuum or overpressure is also possible and an increase in pressure can in some cases lead to an increase in the space-time yield.

The Z-1,2-diarylallyl chlorides of the formula which can be prepared by the process according to the invention<chemistry id="chem0006" num="0006"><img file="EP0409049A2_D0006.tif" /></chemistry>in which the residues R¹ and R² independently of one another hydrogen, halogen, C₁-C₇-Alkyl, C₁-C₆Haloalkyl, C₁-C_s-Alkoxy, C₁-C_s-Halogenalkoxy or an unsubstituted or one to three times by the for R¹ and R² radicals mentioned are substituted aromatic radicals and n is 1, 2 or 3, are also the subject of the invention.

In the formula I, the indices m and n are preferably 1 and the substituents R.¹ and R² independently of each other especially for:

Hydrogen;

Halogen such as fluorine, chlorine, bromine and iodine, preferably chlorine and fluorine; branched or unbranched C₁-C₇-Alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1 , 2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl , 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl;

C._i-C₆Haloalkyl such as fluoromethyl, difluoromethyl, trifluoromethyl, chloridifluoromethyl, dichlorofluoromethyl, trichloromethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2,2,2-difluoroethyl, 2,2 -Dichlor-2-fluoroethyl, 2, 2, 2-trichloroethyl and pentafluoroethyl, preferably trifluoromethyl;

C.₁-C₅Alkoxy such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy and 1,1-dimethylothoxy, preferably methoxy, ethoxy and propoxy;

C.₁-C₅Haloalkoxy such as difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2, 2, 2-trifluoroethoxy, 2-chloro-1,1 , 2-trifluoroethoxy and pentafluoroethoxy, preferably trifluoromethoxy; an aromatic radical, for example a phenyl radical, which is unsubstituted or mono- to trisubstituted by a radical R3 which is the same as R¹ or R² preferably has the meaning given, ie for hydrogen, halogen is a branched or unbranched Ci-C₇-Alkyl group, a Ci-C₆-Halogenalkylgruppe, a Ci-Cs-alkoxy group or a C₁-C₅-Halogenalkoxygruppe stands.

The leftovers R¹ = 4-F and R² = 2-CI are preferred.

Z-1,2-diaryl-allyl chlorides of the general formula I have unexpected advantages over the 1,2-diaryl-allyl bromides known from DE-A 32 18 129. In addition to a very simple epoxidation to the diaryl-oxiranes of the general formula V, it should be mentioned particularly advantageously that stereoselective epoxidation does not result in isomer mixtures of the oxiranes, which is the case based on the known Z-1,2-diarylallyl bromides, but rather such in which the aryl residues are arranged transoid.

For example, the substitution patterns listed in Table 1 below can be present:<tables id="tabl0001" num="0001"><img file="EP0409049A2_D0007.tif" /></tables>

In the diarylallyl chlorides 1, the Z: E isomers can be determined in a known manner, for example by HPLC (high pressure liquid chromatography), by gas chromatography or by ¹H-NMR analysis methods can be determined using the pure Z or E isomers as comparison means and standardization of the corresponding mixing ratios.

The preparation of the fungicidal active ingredients III and IV, starting from the diarylallyl chlorides 1 and the chlorohydrins II, is shown in the following reaction scheme:<chemistry id="chem0007" num="0007"><img file="EP0409049A2_D0008.tif" /></chemistry>

The reaction sequence according to route b) can be carried out in a manner known per se, for example as described in principle in DE-A 32 18 129. The substitution of the chlorine atom by the azole or imidazole group in compound V is usually carried out in an inert solvent such as dimethylformamide or N-methylpyrrolidone in the presence of an inorganic or organic base, such as, for example Sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate or dicyclohexylamine and dimethylcyclohexylamine.

The intermediate products V are new. With regard to the preferred radicals R¹ and R² and the indices n and m, the definitions given in the case of compounds 1 apply analogously. For example, the substitution patterns listed in Table 2 below can be present:<tables id="tabl0002" num="0002"><img file="EP0409049A2_D0009.tif" /></tables>

In the case of route a), the first stage, ie the substitution, proceeds analogously to the last stage of route b). The dehydration and the subsequent substitution can advantageously be carried out in a one-pot process without isolation and purification of intermediate stage II.

According to the invention, the epoxidation of the compounds III is carried out by working in the presence of a high excess of permaleic acid and the permaleic acid in situ from 5 to 30, in particular 5 to 10, molar equivalents of maleic anhydride, based on 111, and less than stoichiometric amounts of hydrogen peroxide solution, based on the maleic anhydride. In general, molar ratios of anhydride to H₂0₂ from 1.5 to 10, in particular 2 to 4, are used. A 30 to 50% aqueous solution of hydrogen peroxide can advantageously be used.

The reaction temperature for the epoxidation can be 0 to 100 ° C., in particular 20 to 80 ° C.

The epoxidation will be carried out in the presence of an aprotic polar solvent. Halogenated hydrocarbons such as dichloromethane, dichloroethane, chlorobenzene or chlorotoluene or aromatic hydrocarbons such as benzene, toluene or xylene can be used as solvents. The amount of solvent is not particularly critical and is generally 5 to 50, in particular 10 to 20,% by weight, based on the olefin.

With this epoxidation method, the azolylmethyloxiranes IV can be obtained in far higher yields than with the processes described in DE-A 32 18 129.

The individual synthesis steps are explained in the following experimental examples.

example 1

Production of the starting materials II

1-chloro-2- (4-chlorophenyl) -3- (2chlorophenyl) propane-2-o1

9.7 g (0.404 mol) of magnesium shavings in 20 ml of absolute ether are at 24 to 36 ° C within 5 min. treated with 5.0 g (0.031 mol) of 2-chlorobenzyl chloride. After the reaction has started, a solution of 200 ml of absolute ether and 50.2 g (0.31 mol) of 2-chlorobenzyl chloride is added dropwise. Then it is refluxed for about 10 minutes. Excess magnesium is decanted off under nitrogen and the Grignard solution is introduced at 0 ° C. 55.7 g (0.3 mol) of para-chloro-ω-chloroacetophenone dissolved in 350 ml of toluene are then added dropwise, and the mixture is stirred at 0 ° C. for a further 1.5 hours. The reaction mixture is added dropwise at about 2 to 6 ° C. to 1.5 l of concentrated ammonium chloride solution. After extraction with methyl tert-butyl ether and subsequent customary workup, 92.9 g (99% yield, HPLC purity: 68.2%) of 1-chloro-2- (4-chlorophenyl) -3- (2- chlorphenyl) propane-2-01 as a crude oil that can be directly converted. For characterization, the product was recrystallized from n-hexane. Melting point: 64 to 69 C.

Examples 2 to 5 and Comparative Examples I to IV

Dehydration of chlorohydrins II

Z-3-chloro-2- (4-chlorophenyl) -1- (2-chlorophenyl) propene (Compound No. 1.16 in Table 1)

60 24.5 g (0.24 mol) of acetic anhydride are added to g (0.2 mol) of the chlorine alcohol described in Example 1 at -2 ° C. in 230 ml of dioxane and 23 ml of tetrahydrofuran and then 2.36 g (0.024 mol) concentrated sulfuric acid added dropwise. After 3 hours of stirring at 0 ° C, practically all starting material has been converted according to HPLC analysis.

A mixture of semi-saturated sodium chloride solution and 50% sodium hydroxide solution is then added at 0 ° C. in the course of 30 minutes, so that a pH of 8 to 9 is established. Finally, the organic phase is dried and concentrated in vacuo and can be used for subsequent reactions without further purification.

Yield 55.7 g (Z / E = 9, 1/1), crude oil, recrystallization to the pure Z isomer from n-hexane with melting point 79 to 82 ° C.

The Z-1,2-diaryl-allyl chlorides according to Table 1 can be prepared in an analogous manner.

Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene (Example No. 1.6 in Table 1)

1-Chloro-2- (4-fluorophenyl) -3- (2-chlorophenyl) propan-2-ol, produced by Grignard addition of 2-chlorobenzylmagnesium chloride to para-fluoro-w-chloroacetophenone and as a raw material with an HPLC purity of 78 -87% used, was implemented as described in Example 2 under the reaction conditions given in Table 2. The proportion of Z or E isomer was determined by HPLC (high pressure liquid chromatography) analysis (uncorrected relative area percentages).<tables id="tabl0003" num="0003"><img file="EP0409049A2_D0010.tif" /></tables><tables id="tabl0004" num="0004"><img file="EP0409049A2_D0011.tif" /></tables>

Example 6

Production of chlorohydrin and in situ dehydration

1-chloro-2- (4-fluorophenyl) -3- (2-chlorophenyl) propan-2-ol

36.0 g (1.5 mol) of magnesium turnings were placed in 200 ml of diethyl ether and 170 g (1.0 mol) of 2-chlorobenzyl chloride dissolved in 400 ml of diethyl ether were added dropwise. 155 g (0.9 mol) of para-fluoro-ω-chloroacetophenone, dissolved in 450 ml of diethyl ether, were then added dropwise at -10.degree. The mixture is then stirred at 25 ° C for 2 hours.

49.0 g (0.5 mol) of concentrated sulfuric acid in 300 ml of diethyl ether are then added dropwise at -10 ° C. The mixture is allowed to warm to 25 ° C. and the salt which has precipitated is filtered off with suction. The crude ethereal solution of chlorohydrin is then used further.

Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene

525 ml of the crude solution described above, with about 134.5 g of chlorohydrin (corresponding to 0.45 mol) are mixed with 8.0 g (0.08 mol) of concentrated sulfuric acid at -10 ° C., and then 57.1 g (0.56 mol) of acetic anhydride were added dropwise within 2 hours. Then a little salt that has precipitated is filtered off again. After evaporation of the solvent from the filtrate, the crude allyl chloride can continue to be used for triazole substitution or for epoxidation.

Example 7

Ketene variant

Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene

At 0 ° C, 250 ml of dioxane, 25 ml of tetrahydrofuran, 12.4 g of acetic acid (0.2 mol) and 69 g (0.23 mol) of crude 1-chloro-2- (obtained from the Grignard reaction according to Example 1 4-fluorophenyl) -3- (2-chlorophenyl) propan-2-ol and 43 g (1.02 mol) of ketene gasified in about 1 hour. After customary working up, a practically identical yield was achieved according to HPLC analysis as when using acetic anhydride in example 2 described above. The Z / E isomer proportions for this reaction are approximately 11: 1.

Examples 8 and 9

Preparation of the Azolylmethyloxirane IV according to route a)

Z-3- (1,2,4Triazol-1-yl) -2- (4chlorophenyl) -1- (2-chlorophenyl) propene

A solution of 11.5 g (0.17 mol) of triazole in 150 ml of dimethylformamide is mixed with 6.6 g of sodium hydroxide and heated to about 70 ° C. until a clear solution is obtained with stirring. The mixture is then cooled to 10 ° C. and 49.5 g of the Z-3-chloro-2- (4-chlorophenyl) -1- (2-chlorophenyl) propene prepared according to Example 2 are dissolved as crude product in 50 ml of dimethylformamide within 1 Added dropwise for an hour and then stirred for a further 4 hours at room temperature.

Then 200 ml of water are added and extracted several times with methyl tert-butyl ether. The combined organic phases are washed, dried and concentrated in vacuo. By recrystallization from methyl tert-butyl ether and n-hexane, 24.4 g of Z-3- (1,2,4-triazol-1-yl) -2- (4-chlorophenyl) -1- (2- chlorophenyl) propene with a melting point of 106-110 ° C.

cis-2- (1,2,4-triazol-1-ylmethyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) oxirane

84 g (0.9 mol) of maleic anhydride and 6 drops of concentrated sulfuric acid are heated in 90 ml of dichloroethane with 22 g of 50% hydrogen peroxide to 50 C and dropwise with 28 g (0.089 mol) of z-3- (1,2,4-triazole -1-yl) -2- (4-fluorophenyl) 1- (2chlorophenyl) propene added in 75 ml dichloroethane. The mixture is subsequently stirred at this temperature for 3 hours and then at 70 ° C. for a further 2.5 hours.

After the reaction mixture has cooled, it is suctioned off from the precipitated maleic acid and extracted with thiosulfate solution and dilute sodium hydroxide solution. The dried organic phase, largely evaporated in vacuo at about 50 ° C., provides 14 g of valuable product after cooling and again concentrating the mother liquor (| ̂ = 50 yield).

Examples 10 and 11

Preparation of Azolylmethyloxirane IV According to Route b)

cis-1-chloromethyl-2- (2-chlorophenyl) -1- (4fluorophenyl) oxirane (Compound No. 2.6 in Table 2)

56.2 g (0.2 mol) of Z-3-chloro-2- (4-fluorophenyl) -1- (2-chlorophenyl) propene are placed in 530 ml of glacial acetic acid with 196 g (2 mol) of maleic anhydride and at 25 C. 68 g (1 mol) of 50% hydrogen peroxide solution were added within one hour. The mixture is stirred for a further 3 to 4 hours at 40 ° C. and then for a further 10 hours at 25 ° C.

Finally, the reaction mixture is stirred into 3 liters of water and 50 ml of 10% sodium thiosulfate solution and, if necessary, a little more thiosulfate solution is added until no more peroxide can be detected. The resulting colorless precipitate is filtered off and dried. The raw material was used without further purification. (Recrystallization from n-hexane; mp. 68 to 70 ° C).

cis-2- (1,2,4-triazol-1-ylmethyl) -2- (4-fluorophenyl) -3- (2-chlorophenyl) oxirane

1.5 g (5 mmol) of cis-1-chloromethyl-2- (2-chlorophenyl) -1- (4-fluorophenyl) oxirane and 0.69 g (7.5 mmol) of sodium 1,2,4-triazolide are stirred for 5 hours in 7 ml of dimethylformamide at 75 ° C. After cooling, the mixture is neutralized by adding a little acetic acid and a little water (about 10 ml) is added, the crystalline product precipitating (yield: 1.4 g). It is suctioned off, washed with water and dried in vacuo.