CZ301063B6 - Process for preparing benzyl cyanide being optionally substituted on benzene ring - Google Patents

Abstract

In the present invention, there is disclosed a process for preparing benzyl cyanide being optionally substituted on a benzene ring with one to three identical or different substituents being selected from the group consisting of halogen atoms, a hydroxy group, an alkyl group containing 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, a trihalomethyl group and N, N-dialkyl amine group containing 1 to 5 carbon atoms in each alkyl radical, wherein benzyl halide, being optionally substituted on a benzene ring as well as the benzyl cyanide, which is to be prepared, is brought into reaction with an alkali metal cyanide, particularly with sodium cyanide in an aliphatic alcohol containing 1 to 3 carbon atoms, particularly in methanol, in the absence of water. Optionally, an alkali metal iodide, particularly sodium iodide is added as a catalyst.

Description

Technical field

The invention relates to a process for the preparation of a benzyl cyanide optionally substituted on a benzene ring with one to three identical or different substituents selected from the group consisting of halogen atoms, hydroxy, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms, trihalomethyl and A dial-dialkylamino group having 1 to 5 carbon atoms in each alkyl radical.

BACKGROUND OF THE INVENTION

The preparation of benzyl cyanide and its derivatives with substituents on the aromatic ring has been described many times, usually in connection with the synthesis of various drugs, pesticides and other chemicals. In such syntheses, benzyl cyanide or its derivatives mostly serve as one of the first intermediates for further chemical modifications, therefore the results of their preparation have a considerable impact on the economics of production of final substances.

The standard procedure for the preparation of benzyl cyanide and its derivatives with substituents on the benzene ring consists in reacting the benzyl halides and their derivatives with sodium or potassium cyanide in a mixture of water and alcohol. The benzyl cyanide preparation process, which was already described in 1922 in the Organic Syntheses Collection of Laws (Vol. 2, p. 9, 1922; Coli. Vol. 1, p. 107, 1941), serves as a model. 500 g (10 mol) of sodium cyanide are dissolved in hot water in 450 ml of water, and a mixture of 1 kg (8 mol) of benzyl chloride (1 kg in 95 kg) is added with stirring over a period of 30 to 45 minutes. After cooling, the precipitated sodium chloride is filtered off, washed with ethanol and ethanol is distilled off from the combined filtrates, and the organic phase is separated from the remaining aqueous phase containing the unreacted excess cyanide together with the rest of the sodium chloride. The crude product obtained is then purified by distillation.

Most of the processes described for the preparation of substituted benzyl cyanides are essentially similar. The differences are only in the details of the implementation - amount and ratio of reactants, solvents, boiling time of the mixture, respectively. by way of product isolation and purification. For example, Eli Lilly (LIS 2,479,295) describes the preparation of 2,4-dichlorobenzyl chloride by boiling 2,4-4 dichlorobenzyl chloride for 7 to 8 hours with a 33% molar excess of potassium cyanide in a mixture of water and 7.5 times the amount of ethanol. The product was not isolated but immediately saponified. A similar 3,4-dichlorobenzyl cyanide was prepared by boiling a mixture of 3,4-dichlorobenzyl bromide with a 25% molar excess of potassium cyanide in an ethanol mixture of 2.5 times the volume of water for 5 hours. Reeve and Pickert (J. Am. Chem. Soc. 1957, 79: 1932-4) used in the preparation of 2,4-dichlorobenzyl cyanide from 2,4-dichlorobenzyl chloride an even twice molar excess of sodium cyanide in ethanol: water 2: 1 and reaction time extended to 20 hours of boiling. Canon and Powell (J. Org. Chem., 1957, 22: 1323-6) required only a 10% excess of sodium cyanide to prepare the same. The reaction medium was a mixture of equal volumes of ethanol and water and the reaction was heated to boiling for 8 hours. Then the ethanol was distilled off, the product was extracted from the aqueous phase into ether, the extract was evaporated and the crude product recrystallized from ethanol. Further product fraction was obtained by concentrating the mother liquor. The overall yield of the substituted benzyl cyanide was 78%. Instead of the aqueous alcohol, in the preparation of 3,4-dichlorobenzyl cyanide (GB 864 108) and 2,3,5-trichlorobenzyl cyanide (EP 0 459 819), the corresponding substituted benzyl bromides, a mixture of dimethylformamide with water was used as reaction medium to prepare 2,3-dichlorobenzyl cyanide ( EP 0 372 934) was even carried out in aqueous dimethylsulfoxide.

From the point of view of the industrial application possibilities of the above processes, it is a disadvantage that most of them generate some amount of aqueous, highly toxic waste containing residual alkali metal cyanide. The use of excess sodium or potassium cyanide in aqueous alkali environments means that after distillation of the alcohol and separation of the organic phase with the product or product extraction, a highly toxic aqueous solution remains which cannot be discharged into the sewer without the destruction of the cyanide. At the same time, waste water detoxification is costly and difficult to carry out. It often results in waste water which, although no longer contains toxic substances, but has a high salinity, which further increases waste disposal costs. Replacing alcohols with more expensive methyl-methyl forms means that when the reaction mixture evaporates the water distills off before the organic solvent with a relatively high boiling point (153 ° C), but the solution is very thermally stressed, evaporation is energy intensive, isolation of pure product is complicated and water is added to the evaporator anyway so that the formation of toxic aqueous waste is not eliminated. Using dimethylsulfoxide boiling at 189 ° C, the solvent was not distilled off, but the reaction mixture was diluted with water and the product extracted into ether. This will only increase the amount of hazardous aqueous waste.

A certain improvement in the processes for the preparation of benzyl cyanide and its derivatives has been brought about by phase transfer catalytic analysis in the reaction of benzyl halides with cyanides in two-phase liquid-liquid, resp. solid - phase liquid. The production of benzylcyanide using quaternary ammonium salts as phase transfer catalysts has been patented by Bayer and Albright and Wilson. Bayer (GB 1 200 970) discloses various process variants using various secondary and tertiary amines as well as quaternary ammonium salts and variously concentrated aqueous sodium cyanide solutions. The starting benzyl chloride and its derivatives were added dropwise to the boiling sodium cyanide solution containing the catalyst over 20 minutes with vigorous stirring, and the mixture was then stirred under boiling for one hour. Sodium cyanide was used with a 1.1 molar excess. After completion of the reaction, the organic phase was separated and the product distilled. The highest yields were obtained using tetradecyldimethylamine, respectively. tetradecyldimethylbenzylammonium chloride, the optimal concentration of the cyanide solution was about 40%.

Albright and Wilson (GB 1 336 883) protected a similar process used for both batch and continuous preparation of benzyl cyanide. The most effective catalysts were quaternary ammonium salts in which one nitrogen-linked alkyl had at least 12 carbon atoms. Tertiary amines were also effective catalysts, of which the quaternary ammonium salt formed directly in the reaction mixture by reaction of the amine with benzyl chloride. The amount of catalyst was 0.5-1.0 mol%. The cyanide was used in the form of a 20-30% aqueous solution, benzyl chloride in most cases used a small molar excess (although the molar ratio seemed to be 1: 1, the NaCN content of the raw material used was 95-97%). The reaction was generally carried out under boiling, with a total reaction time of about 2 hours in the batch process. The yields exceeded 90%. The pH of the reaction mixture ranged between 8-9.5 and the pH of the reaction mixture decreased. In relation to pH values, the patent states that the condition for achieving high yields is to maintain the pH of the reaction mixture below 10.5.

Phase transfer catalysis has also been used in the similar preparation of substituted benzyl cyanides, e.g. 3,5-dichloro-4- (N, N-dimethylamnomethyleneamino) benzyl cyanide (see EP 0 372 934 cited above).

Using phase transfer catalysts, excellent product yields were achieved without using excess cyanide. Nevertheless, this method cannot be considered as a sufficiently large benefit from the technological, economic or environmental point of view compared to the previous processes.

Phase transfer catalysts cannot be rationally regenerated, which makes the process more expensive. Although it is obviously possible to ensure that waste waters are not contaminated with cyanides, high salinity of the waste and contamination of the waste by the catalyst used must be envisaged. This is a highly stable quaternary ammonium salt, which has bactericidal effects and can therefore negatively affect the growth of microorganisms degrading organic components of aqueous waste in biological waste water treatment plants.

A more preferred solution could be to replace soluble quaternary ammonium salts with special anion exchangers, which are actually quaternary ammonium salts immobilized on a polymeric carrier, typically cross-linked polystyrene. This variant of the process, the so-called three-phase catalysis, was studied by Regen (J. Org. Chem., 1977, 42: 875-9), which thus deprived the benzyl cyanide of its 4-chloro-resp. However, the procedure described by Regen was not industrially applicable without further modification (long reaction time, large excess of cyanide). Workers of the chemical compound in Bitterfeld in the former GDR (DD 289 041) patented a similar principle based and more suitable for industrial application for the preparation of benzyl cyanide. They prepared benzyl cyanide by stirring a mixture of an equimolar amount of benzyl chloride and sodium cyanide without solvent with a special ion exchange resin at 90 ° C for 6 hours. The benzyl chloride conversion reached 94.9%. The mixture was then cooled, mixed with water and the catalyst reused after filtration. The disadvantage of the process, however, is that the catalysts used were not commercially available anion exchangers, but materials prepared specifically for this purpose. The commercially available anion exchangers used Sukata for the preparation of benzyl cyanide (J. Org. Chem., 1985, 50 (22): 4388-90), but not as ion exchangers as catalysts but as reaction components, since the ion exchanger was previously converted to cyanide cycle, fully or partially dried and then stirred with benzyl chloride at 65 ° C for 6 hours. However, this process is laborious and does not solve environmental problems with cyanide wastes, but on the contrary worsens, since a considerable amount of aqueous cyanide solution must be lost when converting the ion exchanger into the cyanide cycle.

From an environmental point of view, it is advantageous to completely avoid the use of water in the preparation of benzyl cyanides and their derivatives. One variant of the reaction that allows this is the use of cyclic ethers derived from ethylene glycol, the so-called crown ethers. The cyclic ether with 6 ethyleneoxy groups, 18 ~ crown ~ 6, complexes potassium ions well. The complex formed between potassium cyanide and crown is soluble in organic solvents, where it passes with the cyanide anion. It is not solvated in the solvent, it remains 'naked' and is therefore highly reactive. Substitution reactions carried out in the presence of crown ethers therefore have a high reaction rate. Cook, Bowers and Liotta (J. Org. Chem., 1974, 39 (23): 3416-8) at 100% conversion to benzyl cyanide in benzonitrile in the presence of 18-crown-6 in the reaction of benzyl chloride with a double molar excess of potassium cyanide in acetonitrile. In acetonitrile alone, although the reaction of benzyl chloride with potassium cyanide proceeded without the presence of crown, the yield after stirring for 25 hours was only 20%. Crowns need not be used in stoichiometric, but only catalytic amounts, but their use in the industrial production of benzyl cyanide and its derivatives is uneconomical for a high purchase price and, as a rule, cannot be regenerated and reused. Moreover, acetonitrile is itself a highly toxic solvent.

Expensive cyclic crowns can be replaced by cheaper linear oligomeric ethers of ethylene glycol (JP 56 063949; JP 58 043944) with 6-30 ethyleneoxy groups in the preparation of benzyl cyanides, but the isolation of the product is complicated and even in this case the soluble catalyst cannot be regenerated. The preparation of silacrowns with a catalytic effect exemplified, inter alia, by the preparation of benzyl cyanide (US 4,362,884), which can be covalently bound to an insoluble silicate carrier (porous glass) to obtain regenerable catalysts (US 4,362,884), has also been patented However, their use in industrial production is not an option.

Ando and colleagues (Chem. Letters 1984 (5): 725-8) have replaced ultrasonic phase transfer catalysts in the preparation of benzyl cyanides in a two-phase system. In the presence of alumina, traces of moisture and the application of benzyl bromide and potassium cyanide, ultrasonication results in comparable results to those of crowns. However, the possibilities of using ultrasound in organic synthesis are still limited to the laboratory scale.

The most recent contribution to the problem of preparing benzyl cyanides from benzyl halides and alkali cyanides has been the use of ionic liquids as a substitution reaction medium (Tetrahedron, 2003, 59 (6): 789-794). Ionic fluids such as 1'-butyl-3-methylimidazolinium hexa fluoride phosphate have recently begun to be used as non-volatile solvents in synthetic processes of the so-called "green chemistry" because they can be recycled simply by phase separation, but their cost is too far high for common industrial applications. Their toxicity is also significant.

Another complication, as shown by a team of Japanese authors (Ando, Kazuo; Tokoroyama, Takashi; Kubota, Takashi: Bull. Chem. Soc. Japan 1980, 53 (10): 2885-2890), is that in the reactions of benzyl halides, especially chlorides, but also bromides bearing electron-accepting substituents on the benzene ring, are formed almost always as by-products of phenyl-substituted 2,3-diphenylpropanenitriles when reacted with nucleophilic and at the same time basic alkali metal cyanides. Their formation by competitive reactions, which are preferred at higher temperatures or in an aprotic solvent, can predominate under certain conditions (C. Bamberbey: Chem. Berichte 10, 1886, 2635; A. Kalir, R. Hualem: Synthesis 5, 1987, 514) V. Valenta, A. Dlabanec, M. Protiva: Collect. Czech. Chem. Commun. 46, 1981, 781-791) over the formation of benzyl cyanide, thereby reducing their yield and sometimes complicating their isolation in pure form.

Taking into account existing processes for the preparation of benzyl cyanide and its substituted derivatives from the corresponding benzyl halides, their main disadvantage is either the generation of hazardous, especially saline wastes, which need to be laboriously and costly detoxified, or the use of expensive catalysts and / or equipment. . These disadvantages are overcome by the process described below.

SUMMARY OF THE INVENTION

The present invention provides a process for the preparation of a benzyl cyanide optionally substituted on a benzene ring with one to three identical or different substituents selected from the group consisting of halogen atoms, hydroxy, (C 1 -C 5) alkyl, (C 1 -C 5) alkoxy, trihalomethyl, N, The N-dialkylamino group containing from 1 to 5 carbon atoms in each alkyl radical, by reacting a benzyl halide optionally substituted on the benzene ring as well as the benzyl cyanide to be produced, is reacted with an alkali metal cyanide, which comprises reacting It is carried out in an aliphatic alcohol having 1 to 3 carbon atoms in the absence of water.

Preferably, the alkali metal cyanide is used in an amount of 95 to 99 mol% based on the starting, optionally substituted benzhalide.

Preferably, the reaction is carried out at a temperature of 20 to 80 ° C.

Preferably, the alkali metal cyanide is sodium cyanide.

Preferably, the precipitated sodium halide is separated after completion of the reaction, in particular by filtration or centrifugation. Preferably, after separation of the sodium halide from the filtrate, an aliphatic alcohol containing 1 to 3 carbon atoms is distilled off.

Preferably, methanol is used as the aliphatic alcohol having 1 to 3 carbon atoms.

Preferably, an alkali metal iodide catalyst is added to the reaction mixture. Preferably, sodium iodide is used as the catalyst. Preferably, sodium iodide is used in an amount of 1 to 5 mol. % based on the starting, optionally substituted benzyl halide.

The process for the preparation of the benzyl cyanides according to the invention significantly reduces the formation of by-products, especially aromatic ring substituted 2,3-diphenylpropanenitriles, harmful and toxic wastes, simplifies the finalization of the product in high yield, allows easy recycling of used alcohol as solvent and separation of inorganic salts for possible further use .

Surprisingly, when studying the reaction of benzyl chloride and its derivatives with benzene ring substituents in various solvents, it has been surprisingly shown that when the reaction medium is lower aliphatic alcohols with at most three carbon atoms, preferably methanol, it is not necessary to use sodium or potassium cyanide in aqueous form. solution or to add enough water to the reaction medium to dissolve the cyanide and then proceed in a homogeneous medium. To achieve excellent yields, it was sufficient that the reaction of the benzyl chloride or its derivative with the substituents on the aromatic ring was carried out with finely ground alkali metal cyanide powder. Nor is it necessary to add to the reaction mixture any substance which acts as a phase transfer catalyst. It is utilized here that the alkali metal cyanides partially dissolve in the lower aliphatic alcohols having at most three carbon atoms, preferably in methanol. The solubility of cyanides in anhydrous alcohols is limited and, moreover, decreases as the temperature rises, yet it has been sufficient to effect a virtually complete conversion. The cyanide ions were replaced with chloride ions. Since the sodium chloride formed is practically insoluble in aliphatic alcohols having one to three carbon atoms, it is deposited in the solid state and can be separated by mere filtration. After washing with a small amount of solvent, the solvent used is distilled off from the filtrate, which can be used for the next batch. The distillate residue consists of crude benzyl cyanide or derivatives thereof with substituents on the aromatic ring.

Importantly, the process according to the invention does not give rise to substituted 2,3-diphenylpropanenitrile at all or only to a limited extent, even in the electron-accepting substituents of substituted benzyl halides.

The distillation residue is either purified by distillation; by another process, or is processed without further purification to other products, e.g., hydrolyzed to phenylacetamide or to phenylacetic acid, respectively. to their derivatives with substituents on the aromatic ring.

No excess of cyanide may be used in the process of the present invention. a slightly lower molar amount (eg, an "equimolar" amount without correction for the actual cyanide content, which may be between 97-99% in the raw material used, so that an aralkyl chloride actually uses a 1 to 3% excess). In this case, the precipitated alkali metal chloride does not contain any residual amount of cyanide, so it does not need to be detoxified and can be used for technical purposes, eg (after checking for the absence of cyanides) as a road salt. Since the distilled alcohol can also be used for another batch, the process according to the invention minimizes the negative environmental impacts of production.

Similarly, (substituted) benzyl bromides or benzyl iodides, which are more reactive than the corresponding chlorides, can be converted to the cyander derivatives. In particular, benzyl iodides are characterized by high reactivity, but are usually less readily available. However, they need not be used as isolated products, but can be obtained in situ by the reaction of benzyl chloride or benzyl bromide with an alkali metal iodide. The known fact is that replacement of the chlorine atom in the molecule of the starting material with iodine is easier than the replacement of halogen with a cyano group. The alkali metal iodide does not need to be used in a stoichiometric amount in order to completely exchange the halogen. It is sufficient to use only a catalytic amount, because the benzyl iodide formed reacts rapidly with the cyanide ion. The iodide is formed again and can be reconnected to the reaction sequence. The catalytic effect of iodide addition was utilized, for example, by Sterling Dug Inc. (GB 639 853) for the preparation of 3,4-dichlorobenzylate (cyanide from 3,4-dichlorobenzyl chloride and sodium cyanide in an aqueous alcoholic medium. In a similar preparation of p-tert-butylbenzyl cyanide from p-tert-butylbenzyl chloride and potassium cyanide described by Lednicer ( U.S. Pat. No. 4,065,573) served as a catalyst for potassium iodide, the reaction medium being a mixture of water and methanol, while the reaction time was reduced to only an hour.

Reduced reaction time, resp. The lowering of temperature, in the iodide catalyzed industrial production of benzyl cyanides carried out in a homogeneous aqueous-alcoholic environment, while saving energy and increasing process productivity, does not solve the problems of disposal of hazardous aqueous waste. A study of the course in the environment of the alcohols themselves without the addition of water has shown that the catalytic effect of iodide appears even when the reaction mixture containing powdered cyanide suspended in a solution of benzyl chloride or its derivatives with substituents on the benzene ring in an aliphatic C1-C3 alcohol , preferably in methanol, and adds a catalytic amount of sodium or potassium iodide powder. The sodium or potassium iodide dissolves to a sufficient degree in the alcohol used and its solubility is sufficient to show its catalytic action. Solubility of iodide in alcohols, resp. the limited solubility of the bromide, that is, small solids of inorganic salts dissolved in the alcoholic solution of the product will grow after filtering off the solid. These can then precipitate as a haze when the filtrate is concentrated. In most cases this may not be a malfunction. Where the presence of a small amount of inorganic salt would complicate further purification of the product or treatment, it is possible to get rid of the salt residues by repeating the filtration of the concentrated solution before evaporating the solvent residues or the solvent. precipitation of the salt by addition of a non-polar organic solvent.

The benzyl cyanide or its derivatives with substituents on the benzene ring is generally purified after distillation of the solvent by distillation under reduced pressure. This eliminates extraction operations into volatile flammable or otherwise hazardous organic solvents. The distillation residue, consisting of a small amount of product, unreacted starting benzyl halide, impurities and by-products, is considerably low. It can be disposed of by incineration in an organic chemical waste incinerator, either directly or after dissolution in an organic waste waste such as acetone.

The invention is illustrated by the following examples without limiting the scope of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Example 1

2.4-Dichlorobenzyl chloride (137.6 g, 0.71 mol) was dissolved in 560 mL of methanol. To the solution were added 34.6 g of sodium cyanide powder (98.6% content, 0.70 mol) and 3.5 g (23 mmol) of sodium iodide powder. The reaction mixture was then stirred for 8 hours at 50-52 ° C. After 94-95% conversion of 2,4-dichlorobenzyl chloride and 2-chlorobenzyl chloride respectively. The reaction was quenched, the precipitated sodium chloride was aspirated and washed on the filter with 100 ml of methanol at about 45 ° C. 40.7 g of sodium chloride (0.69 mol) were obtained which, according to the results of the analysis, did not contain starting sodium cyanide. 656 ml of methanol were recovered from the combined filtrates by distillation. The residual oily product was purified by distillation under reduced pressure. Yield

The 2,4-dichlorobenzyl cyanide which distilled at 140-142 ° C / 1.30 kPa was 123.5 g (94.7%). The solid brown distillation residue (about 10 g) was dissolved in waste acetone and handed over for disposal in a hazardous waste incineration plant. M.p. 62-63 ° C (cyclohexane-hexane).

Example 2

3.4- Dichlorobenzyibromide (240 g, 1.0 mol) was dissolved in 750 mL of ethanol. 63 g (98.3%, 0.98 mol) of potassium cyanide were added to the solution, and the reaction mixture was stirred for 11 hours at 60 to 62 ° C. After 94-95% conversion of 3,4-dichlorobenzyl bromide, the reaction was complete, the solution was cooled to 15-20 ° C, the precipitated potassium bromide was filtered off with suction and washed twice with 75 ml of about 45 ° C ethanol on the filter. The combined filtrates were treated as in Example 1. 3,4-Dichlorobenzyl cyanide was distilled under vacuum, collecting 165-170 ° C / 1.60 kPa. Yield 152.5 g (82%). Mp 39-41 ^Q C (hexane).

Example 3

4-Methylbenzyl iodide (116 g, 0.5 mol) was dissolved in 350 mL of methanol, to which was added

31.5 g of potassium cyanide (98.3%, 0.49 mol) of potassium cyanide, the reaction mixture was stirred for 14 hours at the boiling point of methanol. After 95-98% conversion of 4-methylbenzyl iodide was achieved, the reaction mixture was cooled to 10-15 ° C, 400 mL of diethyl ether was added and the precipitated sodium iodide was filtered off (69 g, 0.46 mol), washed with 50 mL of methanol. The combined organic filtrates were stripped of solvents by distillation and the distillation residue was distilled in vacuo. A 4-methylbenzyl cyanide fraction having a boiling point of 135-140 ° C / 50 mm Hg was collected, yield 62.3 g (95%).

Example 4

3-Methoxybenzyl chloride (78.3 g, 0.5 mol) was dissolved in 350 ml methanol, 31.5 g potassium cyanide (98.3%, 0.49 mol) potassium cyanide and 5 g (30 mmol) were added. The stirred mixture was heated at reflux for 12 hours, after reaching 95-98% conversion of 3-methoxybenzyl iodide, the reaction mixture was cooled to room temperature and worked up as outlined in Example 1. 3-Methoxybenzyl cyanide was distilled 145 DEG-150 DEG C./70 mm Hg, 67.7 g (92%).

Example 5

2,5-Dibromobenzyl chloride (71.1 g, 0.25 mol) was dissolved in 500 mL of isopropyl alcohol. To the solution was added 11.8 g of sodium cyanide powder (98.6% content, 0.23 mol) and 1.2 g (8 mmol) of sodium iodide powder. The reaction mixture was then stirred for 9 hours at 60-62 ° C. After 94-95% conversion of 2,5-dibromobenz (chloride or iodide), the reaction was complete, the precipitated sodium chloride was aspirated and washed with 50 ml of methanol at about 45 ° C. The filtrate was freed of methanol by distillation and the solid residue was recrystallized The yield of 2,5-dibromobenzyl cyanide was 62.5 g (91%), m.p. 112 DEG-114 DEG C. (cyclohexane).

Example 6

4-Hydroxybenzyl chloride (71.3 g, 0.5 mol) was dissolved in 380 ml of methanol, to which 23.7 g sodium cyanide (98.6% content, 0.48 mol) and 3.5 g (23 g) were added. mmol) of sodium iodide. The stirred mixture was heated to reflux for 12 hours, achieving a 95-98% conversion of 4-hydroxybenzyl chloride, respectively. The iodide was cooled to room temperature and worked up as outlined in Example 1. The 4-hydroxybenzyl cyanide was distilled under vacuum, collecting fractions 207-212. Yield 59.9 g (90%), m.p. 67-69 ° C (toluene).

Example 7

3,5-Dimethylbenzyl chloride (77.3 g, 0.5 mol) was dissolved in 300 mL of methanol, to which 23.7 g sodium cyanide (98.6% content, 0.48 mol) and 3.5 g were added. (23 mmol) sodium iodide. The stirred mixture was heated at reflux for 12 hours, achieving a 95-98% conversion of 3,5-dimethylbenzyl chloride, respectively. The iodide was cooled to room temperature and worked up as outlined in Example 1. The 3,5-dimethylbenzyl cyanide was distilled off in vacuo, collecting a boiling fraction of 128-132 ° C / 1 mbar. Yield 66.1 g (91%), mp 44-46 ° C (hexane).

Example 8

3,5-Dichlorobenzobromide (120 g, 0.5 mol) was dissolved in 360 ml of ethanol, to the solution was added 31.5 g (98.3%, 0.98 mol) of potassium cyanide, the reaction mixture was stirred for 12

hours at 60-62 ° C. After 94-95% conversion of 3,5-dichlorobenzyl bromide, the reaction was complete, the solution was cooled to 15-20 ° C, the precipitated potassium bromide was aspirated and washed with 75 ml of ethanol at about 45 ° C on the filter. The combined filtrates were treated as in Example 1. 3,5-Dichlorobenzyl cyanide was vacuum distilled, collecting a fraction of 160-165 ° C / 1.60 kPa. Yield 86.7 g (93%). M.p. 139-140 ° C (toluene).

Example 9

4-Trifluoromethylbenzyl chloride (92.6 g, 0.5 mol) was dissolved in 300 mL of methanol, and 23.7 g sodium cyanide (98.6%, 0.48 mol) and 3.5 g (23 g) were added to the solution. mmol) of sodium iodide. The stirred mixture was stirred for 8 hours at 50-52 ° C, achieving a 95-98% conversion of 4-trifluoromethylbenzyl chloride, respectively. The iodide was cooled to room temperature and worked up as outlined in Example 1. 4-Trifluoromethyl benzyl cyanide was distilled off in vacuo, collecting a boiling point of 115-120 ° C / 60 mm Hg. Yield 87.0 g of 4-trifluoromethylbenzyl cyanide (94%), mp 47-49 ° C (cyclohexane).

Example 10

5-Methoxy-2-methylbenzyl chloride (85.3 g, 0.5 mol) was dissolved in 300 ml of methanol, 23.7 g of sodium cyanide (98.6%, 0.48 mol) and 5 g (23 mmol) of sodium iodide. The stirred mixture was heated to reflux for 12 hours, achieving a 95-98% conversion of 3,5-dimethylbenzyl chloride, respectively. of iodide, the reaction mixture was cooled to room temperature and worked up as outlined in Example 5. Yield 55.8 g of 5-methoxy-2-methylbenzyl cyanide (89%), mp 47-49 ° C (cyclohexane).

Example 11

2.4.5- Trichlorobenzyl chloride (115 g, 0.5 mol) was dissolved in 400 ml of methanol, 23.7 g of sodium cyanide (98.6% content, 0.48 mol) and 3.5 g (23 ml) were added to the solution. mmol) of sodium iodide. The stirred mixture was stirred for 6 hours at 50-52 ° C, reaching a 95-98% conversion of 2,4,5-trichlorobenzyl chloride, respectively. of iodide was added to the reaction mixture carboraffin (5 g) and the mixture was filtered. After cooling to 40 ° C, sodium chloride was aspirated and washed with 50 ml of warm methanol. The filtrate was heated to the boiling point of methanol and then 120 ml of warm methanol was added. The filtrate was heated to the boiling point of methanol and then 120 ml of distilled water was added. The mixture was allowed to cool to 15 ° C with stirring over 3 hours where 2,4,5-trichlorobenzyl cyanide crystallized (62 g, 56%). An additional crop of product (32 g, 26%) was obtained from the filtrate after separation of the first fraction of 2,4,5-trichlorobenzyl cyanide by filtration by distilling off 250 ml of methanol and treating the distillation residue as before. Total yield

2.4.5-Trichlorobenzyl cyanide 94.0 g (82%), m.p. 109-110 ° C.

Example 12

2,4,6-Trichlorobenzyl chloride (115 g, 0.5 mol) was dissolved in 400 ml of methanol, 23.7 g of sodium cyanide (98.6% content, 0.48 mol) and 3.5 g were added to the solution. (23 mmol) sodium iodide. The stirred mixture was stirred and heated to reflux for 8 hours, achieving a 95-98% conversion of 2,4,6-trichlorobenzyl chloride, respectively. of iodide was added to the reaction mixture carboraffin (5 g) and the mixture was filtered. After cooling to 40 ° C, sodium chloride was aspirated and washed with 50 ml of warm methanol. The filtrate was heated to the boiling point of methanol and then 200 ml of distilled water was added. The resulting emulsion was allowed to cool to 10 ° C with stirring over 3 hours where 2,4,6-trichlorobenzylcyanide crystallized (70 g, 63.5%). An additional crop of product (27.6 g, 25%) was obtained from of the trichlorobenzyl cyanide fraction by filtration, distilling off 300 ml of methanol and treating the distillation residue as described above. The total yield of 2,4,6-trichlorobenzylcyanide was 97.6 g (88.5%), mp 73-75 ° C.

Claims (10)

A process for the preparation of a benzyl cyanide optionally substituted on a benzene ring with one to three identical or different substituents selected from the group consisting of halogen atoms, hydroxy, alkyl of 1 to 5 carbon atoms, alkoxy of 1 to 5 carbon atoms, trihalomethyl and Ν, A až-dialkylamino group having 1 to 5 carbon atoms in each alkyl moiety, by reacting a benzyl halide optionally substituted on the benzene ring as well as the benzyl cyanide to be produced with an alkali metal cyanide, characterized in that the reaction is carried out in an aliphatic alcohol containing 1 to 5 3 carbon atoms in the absence of water. Process according to claim 1, characterized in that the alkali metal cyanide is used in an amount of 95 to 99% by weight, based on the starting optionally substituted benzyl halide. Process according to claim 1 or 2, characterized in that the reaction is carried out at a temperature of 20 to 80 ° C. Process according to one of claims 1 to 3, characterized in that sodium alkanate is used as the alkali metal cyanide. Process according to one of Claims 1 to 4, characterized in that the precipitated sodium halide is separated after completion of the reaction, in particular by filtration or centrifugation. Process according to Claim 5, characterized in that, after separation of the sodium halide, an aliphatic alcohol containing 1 to 3 carbon atoms is distilled off from the filtrate. Process according to one of Claims 1 to 6, characterized in that methanol is used as the aliphatic alcohol containing 1 to 3 carbon atoms. Process according to any one of claims 1 to 7, characterized in that the reaction mixture is added with an alkali metal iodide catalyst. Process according to Claim 8, characterized in that sodium iodide is used as the catalyst. Process according to Claim 9, characterized in that sodium iodide is used in an amount of 1 to 5 mol%, based on the starting, optionally substituted benzyl halide. End of document